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  1. Transformer model architectures have revolutionized the natural language processing (NLP) domain and continue to produce state-of-the-art results in text-based applications. Prior to the emergence of transformers, traditional NLP models such as recurrent and convolutional neural networks demonstrated promising utility for patient-level predictions and health forecasting from longitudinal datasets. However, to our knowledge only few studies have explored transformers for predicting clinical outcomes from electronic health record (EHR) data, and in our estimation, none have adequately derived a health-specific tokenization scheme to fully capture the heterogeneity of EHR systems. In this study, we propose a dynamic method for tokenizing both discrete and continuous patient data, and present a transformer-based classifier utilizing a joint embedding space for integrating disparate temporal patient measurements. We demonstrate the feasibility of our clinical AI framework through multi-task ICU patient acuity estimation, where we simultaneously predict six mortality and readmission outcomes. Our longitudinal EHR tokenization and transformer modeling approaches resulted in more accurate predictions compared with baseline machine learning models, which suggest opportunities for future multimodal data integrations and algorithmic support tools using clinical transformer networks. 
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  2. Patients in critical care settings often require continuous and multifaceted monitoring. However, current clinical monitoring practices fail to capture important functional and behavioral indices such as mobility or agitation. Recent advances in non-invasive sensing technology, high throughput computing, and deep learning techniques are expected to transform the existing patient monitoring paradigm by enabling and streamlining granular and continuous monitoring of these crucial critical care measures. In this review, we highlight current approaches to pervasive sensing in critical care and identify limitations, future challenges, and opportunities in this emerging field. 
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  3. Keim-Malpass, Jessica (Ed.)
    During the early stages of hospital admission, clinicians use limited information to make decisions as patient acuity evolves. We hypothesized that clustering analysis of vital signs measured within six hours of hospital admission would reveal distinct patient phenotypes with unique pathophysiological signatures and clinical outcomes. We created a longitudinal electronic health record dataset for 75,762 adult patient admissions to a tertiary care center in 2014–2016 lasting six hours or longer. Physiotypes were derived via unsupervised machine learning in a training cohort of 41,502 patients applying consensus k -means clustering to six vital signs measured within six hours of admission. Reproducibility and correlation with clinical biomarkers and outcomes were assessed in validation cohort of 17,415 patients and testing cohort of 16,845 patients. Training, validation, and testing cohorts had similar age (54–55 years) and sex (55% female), distributions. There were four distinct clusters. Physiotype A had physiologic signals consistent with early vasoplegia, hypothermia, and low-grade inflammation and favorable short-and long-term clinical outcomes despite early, severe illness. Physiotype B exhibited early tachycardia, tachypnea, and hypoxemia followed by the highest incidence of prolonged respiratory insufficiency, sepsis, acute kidney injury, and short- and long-term mortality. Physiotype C had minimal early physiological derangement and favorable clinical outcomes. Physiotype D had the greatest prevalence of chronic cardiovascular and kidney disease, presented with severely elevated blood pressure, and had good short-term outcomes but suffered increased 3-year mortality. Comparing sequential organ failure assessment (SOFA) scores across physiotypes demonstrated that clustering did not simply recapitulate previously established acuity assessments. In a heterogeneous cohort of hospitalized patients, unsupervised machine learning techniques applied to routine, early vital sign data identified physiotypes with unique disease categories and distinct clinical outcomes. This approach has the potential to augment understanding of pathophysiology by distilling thousands of disease states into a few physiological signatures. 
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  4. Lai, Yuan (Ed.)
    Mistrust is a major barrier to implementing deep learning in healthcare settings. Entrustment could be earned by conveying model certainty, or the probability that a given model output is accurate, but the use of uncertainty estimation for deep learning entrustment is largely unexplored, and there is no consensus regarding optimal methods for quantifying uncertainty. Our purpose is to critically evaluate methods for quantifying uncertainty in deep learning for healthcare applications and propose a conceptual framework for specifying certainty of deep learning predictions. We searched Embase, MEDLINE, and PubMed databases for articles relevant to study objectives, complying with PRISMA guidelines, rated study quality using validated tools, and extracted data according to modified CHARMS criteria. Among 30 included studies, 24 described medical imaging applications. All imaging model architectures used convolutional neural networks or a variation thereof. The predominant method for quantifying uncertainty was Monte Carlo dropout, producing predictions from multiple networks for which different neurons have dropped out and measuring variance across the distribution of resulting predictions. Conformal prediction offered similar strong performance in estimating uncertainty, along with ease of interpretation and application not only to deep learning but also to other machine learning approaches. Among the six articles describing non-imaging applications, model architectures and uncertainty estimation methods were heterogeneous, but predictive performance was generally strong, and uncertainty estimation was effective in comparing modeling methods. Overall, the use of model learning curves to quantify epistemic uncertainty (attributable to model parameters) was sparse. Heterogeneity in reporting methods precluded the performance of a meta-analysis. Uncertainty estimation methods have the potential to identify rare but important misclassifications made by deep learning models and compare modeling methods, which could build patient and clinician trust in deep learning applications in healthcare. Efficient maturation of this field will require standardized guidelines for reporting performance and uncertainty metrics. 
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  5. Existing pain assessment methods in the intensive care unit rely on patient self-report or visual observation by nurses. Patient self-report is subjective and can suffer from poor recall. In the case of non-verbal patients, behavioral pain assessment methods provide limited granularity, are subjective, and put additional burden on already overworked staff. Previous studies have shown the feasibility of autonomous pain expression assessment by detecting Facial Action Units (AUs). However, previous approaches for detecting facial pain AUs are historically limited to controlled environments. In this study, for the first time, we collected and annotated a pain-related AU dataset, Pain-ICU, containing 55,085 images from critically ill adult patients. We evaluated the performance of OpenFace, an open-source facial behavior analysis tool, and the trained AU R-CNN model on our Pain-ICU dataset. Variables such as assisted breathing devices, environmental lighting, and patient orientation with respect to the camera make AU detection harder than with controlled settings. Although OpenFace has shown state-of-the-art results in general purpose AU detection tasks, it could not accurately detect AUs in our Pain-ICU dataset (F1-score 0.42). To address this problem, we trained the AU R-CNN model on our Pain-ICU dataset, resulting in a satisfactory average F1-score 0.77. In this study, we show the feasibility of detecting facial pain AUs in uncontrolled ICU settings. 
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  6. Advancements in computing and data from the near universal acceptance and implementation of electronic health records has been formative for the growth of personalized, automated, and immediate patient care models that were not previously possible. Artificial intelligence (AI) and its subfields of machine learning, reinforcement learning, and deep learning are well-suited to deal with such data. The authors in this paper review current applications of AI in clinical medicine and discuss the most likely future contributions that AI will provide to the healthcare industry. For instance, in response to the need to risk stratify patients, appropriately cultivated and curated data can assist decision-makers in stratifying preoperative patients into risk categories, as well as categorizing the severity of ailments and health for non-operative patients admitted to hospitals. Previous overt, traditional vital signs and laboratory values that are used to signal alarms for an acutely decompensating patient may be replaced by continuously monitoring and updating AI tools that can pick up early imperceptible patterns predicting subtle health deterioration. Furthermore, AI may help overcome challenges with multiple outcome optimization limitations or sequential decision-making protocols that limit individualized patient care. Despite these tremendously helpful advancements, the data sets that AI models train on and develop have the potential for misapplication and thereby create concerns for application bias. Subsequently, the mechanisms governing this disruptive innovation must be understood by clinical decision-makers to prevent unnecessary harm. This need will force physicians to change their educational infrastructure to facilitate understanding AI platforms, modeling, and limitations to best acclimate practice in the age of AI. By performing a thorough narrative review, this paper examines these specific AI applications, limitations, and requisites while reviewing a few examples of major data sets that are being cultivated and curated in the US. 
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  7. Bondi, Mark (Ed.)
    Background: Advantages of digital clock drawing metrics for dementia subtype classification needs examination. Objective: To assess how well kinematic, time-based, and visuospatial features extracted from the digital Clock Drawing Test (dCDT) can classify a combined group of Alzheimer’s disease/Vascular Dementia patients versus healthy controls (HC), and classify dementia patients with Alzheimer’s disease (AD) versus vascular dementia (VaD). Methods: Healthy, community-dwelling control participants (n = 175), patients diagnosed clinically with Alzheimer’s disease (n = 29), and vascular dementia (n = 27) completed the dCDT to command and copy clock drawing conditions. Thirty-seven dCDT command and 37 copy dCDT features were extracted and used with Random Forest classification models. Results: When HC participants were compared to participants with dementia, optimal area under the curve was achieved using models that combined both command and copy dCDT features (AUC = 91.52%). Similarly, when AD versus VaD participants were compared, optimal area under the curve was, achieved with models that combined both command and copy features (AUC = 76.94%). Subsequent follow-up analyses of a corpus of 10 variables of interest determined using a Gini Index found that groups could be dissociated based on kinematic, time-based, and visuospatial features. Conclusion: The dCDT is able to operationally define graphomotor output that cannot be measured using traditional paper and pencil test administration in older health controls and participants with dementia. These data suggest that kinematic, time-based, and visuospatial behavior obtained using the dCDT may provide additional neurocognitive biomarkers that may be able to identify and tract dementia syndromes. 
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  8. The complexity of transplant medicine pushes the boundaries of innate, human reasoning. From networks of immune modulators to dynamic pharmacokinetics to variable postoperative graft survival to equitable allocation of scarce organs, machine learning promises to inform clinical decision making by deciphering prodigious amounts of available data. This paper reviews current research describing how algorithms have the potential to augment clinical practice in solid organ transplantation. We provide a general introduction to different machine learning techniques, describing their strengths, limitations, and barriers to clinical implementation. We summarize emerging evidence that recent advances that allow machine learning algorithms to predict acute post-surgical and long-term outcomes, classify biopsy and radiographic data, augment pharmacologic decision making, and accurately represent the complexity of host immune response. Yet, many of these applications exist in pre-clinical form only, supported primarily by evidence of single-center, retrospective studies. Prospective investigation of these technologies has the potential to unlock the potential of machine learning to augment solid organ transplantation clinical care and health care delivery systems. 
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