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Background: Reinforcement learning (RL) holds great promise for intensive care medicine given the abundant availability of data and frequent sequential decision-making. But despite the emergence of promising algorithms, RL driven bedside clinical decision support is still far from reality. Major challenges include trust and safety. To help address these issues, we introduce cross off-policy evaluation and policy restriction and show how detailed policy analysis may increase clinical interpretability. As an example, we apply these in the setting of RL to optimise ventilator settings in intubated covid-19 patients. Methods: With data from the Dutch ICU Data Warehouse and using an exhaustive hyperparameter grid search, we identified an optimal set of Dueling Double-Deep Q Network RL models. The state space comprised ventilator, medication, and clinical data. The action space focused on positive end-expiratory pressure (peep) and fraction of inspired oxygen (FiO2) concentration. We used gas exchange indices as interim rewards, and mortality and state duration as final rewards. We designed a novel evaluation method called cross off-policy evaluation (OPE) to assess the efficacy of models under varying weightings between the interim and terminal reward components. In addition, we implemented policy restriction to prevent potentially hazardous model actions. We introduce delta-Q to compare physician versus policy action quality and in-depth policy inspection using visualisations. Results: We created trajectories for 1118 intensive care unit (ICU) admissions and trained 69,120 models using 8 model architectures with 128 hyperparameter combinations. For each model, policy restrictions were applied. In the first evaluation step, 17,182/138,240 policies had good performance, but cross-OPE revealed suboptimal performance for 44% of those by varying the reward function used for evaluation. Clinical policy inspection facilitated assessment of action decisions for individual patients, including identification of action space regions that may benefit most from optimisation. Conclusion: Cross-OPE can serve as a robust evaluation framework for safe RL model implementation by identifying policies with good generalisability. Policy restriction helps prevent potentially unsafe model recommendations. Finally, the novel delta-Q metric can be used to operationalise RL models in clinical practice. Our findings offer a promising pathway towards application of RL in intensive care medicine and beyond. [ABSTRACT FROM AUTHOR]

Background: Identification of clinical phenotypes in critically ill COVID-19 patients could improve understanding of the disease heterogeneity and enable prognostic and predictive enrichment. However, previous attempts did not take into account temporal dynamics with high granularity. By including the dimension of time, we aim to gain further insights into the heterogeneity of COVID-19. Methods: We used granular data from 3202 adult COVID patients in the Dutch Data Warehouse that were admitted to one of 25 Dutch ICUs between February 2020 and March 2021. Parameters including demographics, clinical observations, medications, laboratory values, vital signs, and data from life support devices were selected. Twenty-one datasets were created that each covered 24 h of ICU data for each day of ICU treatment. Clinical phenotypes in each dataset were identified by performing cluster analyses. Both evolution of the clinical phenotypes over time and patient allocation to these clusters over time were tracked. Results: The final patient cohort consisted of 2438 COVID-19 patients with a ICU mortality outcome. Forty-one parameters were chosen for cluster analysis. On admission, both a mild and a severe clinical phenotype were found. After day 4, the severe phenotype split into an intermediate and a severe phenotype for 11 consecutive days. Heterogeneity between phenotypes appears to be driven by inflammation and dead space ventilation. During the 21-day period, only 8.2% and 4.6% of patients in the initial mild and severe clusters remained assigned to the same phenotype respectively. The clinical phenotype half-life was between 5 and 6 days for the mild and severe phenotypes, and about 3 days for the medium severe phenotype. Conclusions: Patients typically do not remain in the same cluster throughout intensive care treatment. This may have important implications for prognostic or predictive enrichment. Prominent dissimilarities between clinical phenotypes are predominantly driven by inflammation and dead space ventilation. [ABSTRACT FROM AUTHOR]

In population pharmacokinetic (PK) models, interindividual variability is explained by implementation of covariates in the model. The widely used forward stepwise selection method is sensitive to bias, which may lead to an incorrect inclusion of covariates. Alternatives, such as the full fixed effects model, reduce this bias but are dependent on the chosen implementation of each covariate. As the correct functional forms are unknown, this may still lead to an inaccurate selection of covariates. Machine learning (ML) techniques can potentially be used to learn the optimal functional forms for implementing covariates directly from data. A recent study suggested that using ML resulted in an improved selection of influential covariates. However, how do we select the appropriate functional form for including these covariates? In this work, we use SHapley Additive exPlanations (SHAP) to infer the relationship between covariates and PK parameters from ML models. As a case‐study, we use data from 119 patients with hemophilia A receiving clotting factor VIII concentrate peri‐operatively. We fit both a random forest and a XGBoost model to predict empirical Bayes estimated clearance and central volume from a base nonlinear mixed effects model. Next, we show that SHAP reveals covariate relationships which match previous findings. In addition, we can reveal subtle effects arising from combinations of covariates difficult to obtain using other methods of covariate analysis. We conclude that the proposed method can be used to extend ML‐based covariate selection, and holds potential as a complete full model alternative to classical covariate analyses. [ABSTRACT FROM AUTHOR]

Deep reinforcement learning (DRL) has shown remarkable success in artificial domains and in some real-world applications. However, substantial challenges remain such as learning efficiently under safety constraints. Adherence to safety constraints is a hard requirement in many high-impact application domains such as healthcare and finance. These constraints are preferably represented symbolically to ensure clear semantics at a suitable level of abstraction. Existing approaches to safe DRL assume that being unsafe leads to low rewards. We show that this is a special case of symbolically constrained RL and analyze a generic setting in which total reward and being safe may or may not be correlated. We analyze the impact of symbolic constraints and identify a connection between expected future reward and distance towards a goal in an automaton representation of the constraints. We use this connection in an algorithm for learning complex behaviors safely and efficiently. This algorithm relies on symbolic reasoning over safety constraints to improve the efficiency of a subsymbolic learner with a symbolically obtained measure of progress. We measure sample efficiency on a grid world and a conversational product recommender with real-world constraints. The so-called Planning for Potential algorithm converges quickly and significantly outperforms all baselines. Specifically, we find that symbolic reasoning is necessary for safety during and after learning and can be effectively used to guide a neural learner towards promising areas of the solution space. We conclude that RL can be applied both safely and efficiently when combined with symbolic reasoning. [ABSTRACT FROM AUTHOR]

Energy disaggregation, a.k.a. Non-Intrusive Load Monitoring, aims to separate the energy consumption of individual appliances from the readings of a mains power meter measuring the total energy consumption of, e.g., a whole house. Energy consumption of individual appliances can be useful in many applications, e.g., providing appliance-level feedback to the end users to help them understand their energy consumption and ultimately save energy. Recently, with the availability of large-scale energy consumption datasets, various neural network models such as convolutional neural networks and recurrent neural networks have been investigated to solve the energy disaggregation problem. Neural network models can learn complex patterns from large amounts of data and have been shown to outperform the traditional machine learning methods such as variants of hiddenMarkov models. However, current neural network methods for energy disaggregation are either computational expensive or are not capable of handling long-term dependencies. In this article, we investigate the application of the recently developed WaveNet models for the task of energy disaggregation. Based on a real-world energy dataset collected from 20 households over 2 years, we show thatWaveNet models outperforms the state-of-the-art deep learning methods proposed in the literature for energy disaggregation in terms of both error measures and computational cost. On the basis of energy disaggregation, we then investigate the performance of two deep-learning based frameworks for the task of on/off detection which aims at estimating whether an appliance is in operation or not. The first framework obtains the on/off states of an appliance by binarising the predictions of a regression model trained for energy disaggregation, while the second framework obtains the on/off states of an appliance by directly training a binary classifier with binarised energy readings of the appliance serving as the target values. Based on the same dataset, we show that for the task of on/off detection the second framework, i.e., directly training a binary classifier, achieves better performance in terms of F1 score. [ABSTRACT FROM AUTHOR]

Purpose: Early clinical recognition of sepsis can be challenging. With the advancement of machine learning, promising real-time models to predict sepsis have emerged. We assessed their performance by carrying out a systematic review and meta-analysis.Methods: A systematic search was performed in PubMed, Embase.com and Scopus. Studies targeting sepsis, severe sepsis or septic shock in any hospital setting were eligible for inclusion. The index test was any supervised machine learning model for real-time prediction of these conditions. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, with a tailored Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) checklist to evaluate risk of bias. Models with a reported area under the curve of the receiver operating characteristic (AUROC) metric were meta-analyzed to identify strongest contributors to model performance.Results: After screening, a total of 28 papers were eligible for synthesis, from which 130 models were extracted. The majority of papers were developed in the intensive care unit (ICU, n = 15; 54%), followed by hospital wards (n = 7; 25%), the emergency department (ED, n = 4; 14%) and all of these settings (n = 2; 7%). For the prediction of sepsis, diagnostic test accuracy assessed by the AUROC ranged from 0.68-0.99 in the ICU, to 0.96-0.98 in-hospital and 0.87 to 0.97 in the ED. Varying sepsis definitions limit pooling of the performance across studies. Only three papers clinically implemented models with mixed results. In the multivariate analysis, temperature, lab values, and model type contributed most to model performance.Conclusion: This systematic review and meta-analysis show that on retrospective data, individual machine learning models can accurately predict sepsis onset ahead of time. Although they present alternatives to traditional scoring systems, between-study heterogeneity limits the assessment of pooled results. Systematic reporting and clinical implementation studies are needed to bridge the gap between bytes and bedside. [ABSTRACT FROM AUTHOR]

Background Self-reported client assessments during online treatments enable the development of statistical models for the prediction of client improvement and symptom development. Evaluation of these models is mandatory to ensure their validity. Methods For this purpose, we suggest besides a model evaluation based on study data the use of a simulation analysis. The simulation analysis provides insight into the model performance and enables to analyse reasons for a low predictive accuracy. In this study, we evaluate a temporal causal model (TCM) and show that it does not provide reliable predictions of clients' future mood levels. Results Based on the simulation analysis we investigate the potential reasons for the low predictive performance, for example, noisy measurements and sampling frequency. We conclude that the analysed TCM in its current form is not sufficient to describe the underlying psychological processes. Conclusions The results demonstrate the importance of model evaluation and the benefit of a simulation analysis. The current manuscript provides practical guidance for conducting model evaluation including simulation analysis. [ABSTRACT FROM AUTHOR]

Predicting therapeutic outcome in the mental health domain is of utmost importance to enable therapists to provide the most effective treatment to a patient. Using information from the writings of a patient can potentially be a valuable source of information, especially now that more and more treatments involve computer-based exercises or electronic conversations between patient and therapist. In this paper, we study predictive modeling using writings of patients under treatment for a social anxiety disorder. We extract a wealth of information from the text written by patients including their usage of words, the topics they talk about, the sentiment of the messages, and the style of writing. In addition, we study trends over time with respect to those measures. We then apply machine learning algorithms to generate the predictive models. Based on a dataset of 69 patients, we are able to show that we can predict therapy outcome with an area under the curve of 0.83 halfway through the therapy and with a precision of 0.78 when using the full data (i.e., the entire treatment period). Due to the limited number of participants, it is hard to generalize the results, but they do show great potential in this type of information. [ABSTRACT FROM AUTHOR]

More than a decade after the first extensive overview on parameter control, we revisit the field and present a survey of the state-of-the-art. We briefly summarize the development of the field and discuss existing work related to each major parameter or component of an evolutionary algorithm. Based on this overview, we observe trends in the area, identify some (methodological) shortcomings, and give recommendations for future research. [ABSTRACT FROM AUTHOR]

Using a pure machine learning approach to enable the generation of behavior for agents in serious gaming applications can be problematic, because such applications often require human-like behavior for agents that interact with human players. Such human-like behavior is not guaranteed with e.g. basic reinforcement learning schemes. Cognitive models can be very useful to establish human-like behavior in an agent. However, they require ample domain knowledge that might be difficult to obtain. In this paper, a cognitive model is taken as a basis, and the addition of scenario specific information is for a large part automated by means of machine learning techniques. The performance of the approach of automatically adding scenario specific information is rigorously evaluated using a case study in the domain of fighter air combat. An evolutionary algorithm is proposed for automatically tailoring a cognitive model for situation awareness of fighter pilots. The standard algorithm and several extensions are evaluated with respect to performance in air combat. The results show that it is possible to apply the algorithm to optimize belief networks for cognitive models of intelligent agents (adversarial fighters) in the aforementioned domain, thereby reducing the effort required to elicit knowledge from experts, while retaining the required 'human-like' behavior. [ABSTRACT FROM AUTHOR]