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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]

Objective: Machine learning techniques can be used to extract predictive models for diseases from electronic medical records (EMRs). However, the nature of EMRs makes it difficult to apply off-the-shelf machine learning techniques while still exploiting the rich content of the EMRs. In this paper, we explore the usage of a range of natural language processing (NLP) techniques to extract valuable predictors from uncoded consultation notes and study whether they can help to improve predictive performance.Methods: We study a number of existing techniques for the extraction of predictors from the consultation notes, namely a bag of words based approach and topic modeling. In addition, we develop a dedicated technique to match the uncoded consultation notes with a medical ontology. We apply these techniques as an extension to an existing pipeline to extract predictors from EMRs. We evaluate them in the context of predictive modeling for colorectal cancer (CRC), a disease known to be difficult to diagnose before performing an endoscopy.Results: Our results show that we are able to extract useful information from the consultation notes. The predictive performance of the ontology-based extraction method moves significantly beyond the benchmark of age and gender alone (area under the receiver operating characteristic curve (AUC) of 0.870 versus 0.831). We also observe more accurate predictive models by adding features derived from processing the consultation notes compared to solely using coded data (AUC of 0.896 versus 0.882) although the difference is not significant. The extracted features from the notes are shown be equally predictive (i.e. there is no significant difference in performance) compared to the coded data of the consultations.Conclusion: It is possible to extract useful predictors from uncoded consultation notes that improve predictive performance. Techniques linking text to concepts in medical ontologies to derive these predictors are shown to perform best for predicting CRC in our EMR dataset. [ABSTRACT FROM AUTHOR]

Abstract: When considering intelligent agents that interact with humans, having an idea of the trust levels of the human, for example in other agents or services, can be of great importance. Most models of human trust that exist assume trust in one trustee is independent of trust in another trustee. The model introduced here addresses so-called relative trust. The idea of relative trust is that trust in a certain trustee not only depends on the experiences with that trustee, but also on trustees that are perceived competitors of that trustee. Such models for relative trust contain parameters to represent the specific dependency between trust for different trustees. In order to tailor the model towards a specific human, dedicated parameter estimation techniques are used. The validation shows that such a model for relative trust is able to predict human trust based behavior significantly better compared to a benchmark model. [Copyright &y& Elsevier]

A model-based agent system model for medicine usage management is presented and formally analysed. The model incorporates an intelligent ambient agent model that has an explicit representation of a dynamical system model to estimate the medicine level in the patient s body by simulation, is able to analyse whether the patient intends to take the medicine too early or too late, and can take measures to prevent this. [ABSTRACT FROM AUTHOR]

Within human trust related behaviour, according to the literature from the domains of Psychology and Social Sciences often non-rational behaviour can be observed. Current trust models that have been developed typically do not incorporate non-rational elements in the trust formation dynamics. In order to enable agents that interact with humans to have a good estimation of human trust, and take this into account in their behaviour, trust models that incorporate such human aspects are a necessity. A specific non-rational element in humans is that they are often biased in their behaviour. In this paper, models for human trust dynamics are presented incorporating human biases. In order to show that they more accurately describe human behaviour, they have been evaluated against empirical data, which shows that the models perform significantly better. [ABSTRACT FROM AUTHOR]

Abstract: In this paper a computational model is presented for how a desire triggers responses and feelings. The model shows how these feelings can be biased, for example due to addicting experiences in the past. Both the strength of a response and of the associated feeling result from a converging dynamic pattern modeled by reciprocal causal interactions between the two. The model has been used to conduct a number of simulation experiments under varying circumstances. Moreover, it has been evaluated by formal analysis of emerging patterns entailed by the model. Furthermore, it has been pointed out how the computational model can be applied within an ambient agent system supporting a human in not being tempted. In a simple example scenario it is shown such an ambient agent system is able to predict and assess a human’s desire state, and use this assessment to suggest alternatives to avoid falling for certain temptations. [Copyright &y& Elsevier]

Abstract: Trust dynamics can be modeled in relation to experiences. In this paper two models to represent human trust dynamics are introduced, namely a model on a cognitive level and a neural model. These models include a number of parameters, providing the possibility to express certain relations between trustees. The behavior of each of the models is further analyzed by means of simulation experiments and formal verification techniques. Thereafter, both models have been compared to see whether they can produce patterns that are comparable. As each of the models has its own specific set of parameters, with values that depend on the type of person modeled, such a comparison is non-trivial. To address this, a special comparison approach is introduced, based on mutual mirroring of the models in each other. More specifically, for a given parameter values set for one model, by an automated parameter estimation procedure the most optimal values for the parameter values of the other model are determined in order to show the same behavior. Roughly spoken the results are that the models can mirror each other up to an accuracy of around 90%. [Copyright &y& Elsevier]

Abstract: This paper presents analysis and simulation of meta-reasoning processes based on an agent-based meta-level architecture for strategic reasoning in naval planning. The architecture was designed as a generic agent model and instantiated with decision knowledge acquired from naval domain experts and was specified as an executable agent-based model which has been used to perform a number of simulations. To evaluate the simulation results, relevant properties for the planning decision were identified and formalized. These properties have been validated for the simulation traces. [Copyright &y& Elsevier]

Abstract: This paper presents an agent-based approach for error detection in incident management organizations. The approach consists of several parts. First, a formal approach for the specification and hierarchical verification of both traces and properties. Incomplete traces are enriched by enrichment rules. Furthermore, a classification mechanism is presented for the different properties in incident management that is based on psychological literature. Classification of errors provides insight in the functioning of the agents involved with respect to their roles. This insight enables the provision of dedicated training sessions and allows software support to give appropriate warning messages during incident management. [Copyright &y& Elsevier]

Organizations involving multiple agents require adaptation mechanisms to guarantee robustness, especially in critical domains. This paper presents an organizational template to aid analysis and design of organizations with adaptation mechanisms based on dynamic role reallocation. The adaptive organization model can be used both for qualitative and quantitative domains, as is shown in two application cases made to evaluate the applicability of the model. [ABSTRACT FROM AUTHOR]

The ability to express preferences for specific tasks in multi-agent auctions is an important element for potential users who are considering to use such auctioning systems. This paper presents an approach to make such preferences explicit and to use these preferences in bids for reverse combinatorial auctions. Three different types of preference are considered: (1) preferences for particular durations of tasks, (2) preferences for certain time points, and (3) preferences for specific types of tasks. We study empirically the tradeoffs between the quality of the solutions obtained and the use of preferences in the bidding process, focusing on effects such as increased execution time. We use both synthetic data as well as real data from a logistics company. [ABSTRACT FROM AUTHOR]

Abstract: Within the field of incident management split second decisions have to be made, usually on the basis of incomplete and partially incorrect information. As a result of these conditions, errors occur in such decision processes. In order to avoid repetition of such errors, historic cases, disaster plans, and training logs need to be thoroughly analysed. This paper presents a formal approach for such an analysis that pays special attention to spatial and temporal aspects, to information exchange, and to organisational structure. The formal nature of the approach enables automation of analysis, which is illustrated by case studies of two disasters. [Copyright &y& Elsevier]

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]

OBJECTIVE: Reinforcement learning (RL) is a machine learning technique uniquely effective at sequential decision-making, which makes it potentially relevant to ICU treatment challenges. We set out to systematically review, assess level-of-readiness and meta-analyze the effect of RL on outcomes for critically ill patients. DATA SOURCES: A systematic search was performed in PubMed, Embase.com, Clarivate Analytics/Web of Science Core Collection, Elsevier/SCOPUS and the Institute of Electrical and Electronics Engineers Xplore Digital Library from inception to March 25, 2022, with subsequent citation tracking. DATA EXTRACTION: Journal articles that used an RL technique in an ICU population and reported on patient health-related outcomes were included for full analysis. Conference papers were included for level-of-readiness assessment only. Descriptive statistics, characteristics of the models, outcome compared with clinician's policy and level-of-readiness were collected. RL-health risk of bias and applicability assessment was performed. DATA SYNTHESIS: A total of 1,033 articles were screened, of which 18 journal articles and 18 conference papers, were included. Thirty of those were prototyping or modeling articles and six were validation articles. All articles reported RL algorithms to outperform clinical decision-making by ICU professionals, but only in retrospective data. The modeling techniques for the state-space, action-space, reward function, RL model training, and evaluation varied widely. The risk of bias was high in all articles, mainly due to the evaluation procedure. CONCLUSION: In this first systematic review on the application of RL in intensive care medicine we found no studies that demonstrated improved patient outcomes from RL-based technologies. All studies reported that RL-agent policies outperformed clinician policies, but such assessments were all based on retrospective off-policy evaluation. [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]

• Machine learning has the potential to improve the positive predictive value of neonatal screening for primary and central congenital hypothyroidism. • Currently, detection of central congenital hypothyroidism is accompanied by a high number of false-positives. • In order of importance, variables determining detection of congenital hypothyroidism were TSH, T4/TBG, (gestational) age, TBG, T4, and age at NBS sampling. • From the current routine screening parameters, T4/TBG is the most important parameter to detect central congenital hypothyroidism with a low positive predictive value. • New screening parameters are needed to improve the detection of central congenital hypothyroidism. The Dutch Congenital hypothyroidism (CH) Newborn Screening (NBS) algorithm for thyroidal and central congenital hypothyroidism (CH-T and CH-C, respectively) is primarily based on determination of thyroxine (T4) concentrations in dried blood spots, followed by thyroid-stimulating hormone (TSH) and thyroxine-binding globulin (TBG) measurements enabling detection of both CH-T and CH-C, with a positive predictive value (PPV) of 21%. A calculated T4/TBG ratio serves as an indirect measure for free T4. The aim of this study is to investigate whether machine learning techniques can help to improve the PPV of the algorithm without missing the positive cases that should have been detected with the current algorithm. NBS data and parameters of CH patients and false-positive referrals in the period 2007–2017 and of a healthy reference population were included in the study. A random forest model was trained and tested using a stratified split and improved using synthetic minority oversampling technique (SMOTE). NBS data of 4668 newborns were included, containing 458 CH-T and 82 CH-C patients, 2332 false-positive referrals and 1670 healthy newborns. Variables determining identification of CH were (in order of importance) TSH, T4/TBG ratio, gestational age, TBG, T4 and age at NBS sampling. In a Receiver-Operating Characteristic (ROC) analysis on the test set, current sensitivity could be maintained, while increasing the PPV to 26%. Machine learning techniques have the potential to improve the PPV of the Dutch CH NBS. However, improved detection of currently missed cases is only possible with new, better predictors of especially CH-C and a better registration and inclusion of these cases in future models. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVES: Outcome prediction of preterm birth is important for neonatal care, yet prediction performance using conventional statistical models remains insufficient. Machine learning has a high potential for complex outcome prediction. In this scoping review, we provide an overview of the current applications of machine learning models in the prediction of neurodevelopmental outcomes in preterm infants, assess the quality of the developed models, and provide guidance for future application of machine learning models to predict neurodevelopmental outcomes of preterm infants. METHODS: A systematic search was performed using PubMed. Studies were included if they reported on neurodevelopmental outcome prediction in preterm infants using predictors from the neonatal period and applying machine learning techniques. Data extraction and quality assessment were independently performed by 2 reviewers. RESULTS: Fourteen studies were included, focusing mainly on very or extreme preterm infants, predicting neurodevelopmental outcome before age 3 years, and mostly assessing outcomes using the Bayley Scales of Infant Development. Predictors were most often based on MRI. The most prevalent machine learning techniques included linear regression and neural networks. None of the studies met all newly developed quality assessment criteria. Studies least prone to inflated performance showed promising results, with areas under the curve up to 0.86 for classification and R² values up to 91% in continuous prediction. A limitation was that only 1 data source was used for the literature search. CONCLUSIONS: Studies least prone to inflated prediction results are the most promising. The provided evaluation framework may contribute to improved quality of future machine learning models. [ABSTRACT FROM AUTHOR]

Reinforcement Learning (RL) has recently found many applications in the healthcare domain thanks to its natural fit to clinical decision-making and ability to learn optimal decisions from observational data. A key challenge in adopting RL-based solution in clinical practice, however, is the inclusion of existing knowledge in learning a suitable solution. Existing knowledge from e.g. medical guidelines may improve the safety of solutions, produce a better balance between short- and long-term outcomes for patients and increase trust and adoption by clinicians. We present a framework for including knowledge available from medical guidelines in RL. The framework includes components for enforcing safety constraints and an approach that alters the learning signal to better balance short- and long-term outcomes based on these guidelines. We evaluate the framework by extending an existing RL-based mechanical ventilation (MV) approach with clinically established ventilation guidelines. Results from off-policy policy evaluation indicate that our approach has the potential to decrease 90-day mortality while ensuring lung protective ventilation. This framework provides an important stepping stone towards implementations of RL in clinical practice and opens up several avenues for further research. • Reinforcement learning based on observational data and existing knowledge. • Treatment advice and physiological knowledge in guidelines are injected into learner. • Ventilation case study indicates adherence to guidelines, clinician outperformance. [ABSTRACT FROM AUTHOR]

Central research questions addressed within Criminology are how the geographical displacement of crime can be understood, explained, and predicted. The process of crime displacement is usually explained by referring to the interaction of three types of agents: criminals, passers-by, and guardians. Most existing simulation models of this process take a 'local' perspective, i.e., they are agent-based. However, when the number of agents considered becomes large, more 'global' approaches, such as population-based simulation have computational advantages over agent-based simulation. This article presents both an agent-based and a population-based simulation model of crime displacement, and reports a comparative evaluation of the two models. In addition, an approach is put forward to analyse the behaviour of both models by means of formal techniques. The results suggest that under certain conditions, population-based models approximate agent-based models, at least in the domain under investigation. [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]

Abstract: Within agent-based Ambient Intelligence applications agents react to humans based on information obtained by sensoring and their knowledge about human functioning. Appropriate types of reactions depend on the extent to which an agent understands the human and is able to interpret the available information (which is often incomplete, and hence multi-interpretable) in order to create a more complete internal image of the environment, including humans. Such an understanding requires that the agent has knowledge to a certain depth about the human’s physiological and mental processes in the form of an explicitly represented model of the causal and dynamic relations describing these processes. In addition, given such a model representation, the agent needs reasoning methods to derive conclusions from the model and interpret the (partial) information available by sensoring. This paper presents the development of a toolbox that can be used by a modeller to design Ambient Intelligence applications. This toolbox contains a number of model-based reasoning methods and approaches to control such reasoning methods. Formal specifications in an executable temporal format are offered, which allows for simulation of reasoning processes and automated verification of the resulting reasoning traces in a dedicated software environment. A number of such simulation experiments and their formal analysis are described. The main contribution of this paper is that the reasoning methods in the toolbox have the possibility to reason using both quantitative and qualitative aspects in combination with a temporal dimension, and the possibility to perform focused reasoning based upon certain heuristic information. [Copyright &y& Elsevier]

Introduction: In recent years, reinforcement learning (RL) has gained traction in the healthcare domain. In particular, RL methods have been explored for haemodynamic optimization of septic patients in the Intensive Care Unit. Most hospitals however, lack the data and expertise for model development, necessitating transfer of models developed using external datasets. This approach assumes model generalizability across different patient populations, the validity of which has not previously been tested. In addition, there is limited knowledge on safety and reliability. These challenges need to be addressed to further facilitate implementation of RL models in clinical practice.Method: We developed and validated a new reinforcement learning model for hemodynamic optimization in sepsis on the MIMIC intensive care database from the USA using a dueling double deep Q network. We then transferred this model to the European AmsterdamUMCdb intensive care database. T-Distributed Stochastic Neighbor Embedding and Sequential Organ Failure Assessment scores were used to explore the differences between the patient populations. We apply off-policy policy evaluation methods to quantify model performance. In addition, we introduce and apply a novel deep policy inspection to analyse how the optimal policy relates to the different phases of sepsis and sepsis treatment to provide interpretable insight in order to assess model safety and reliability.Results: The off-policy evaluation revealed that the optimal policy outperformed the physician policy on both datasets despite marked differences between the two patient populations and physician's policies. Our novel deep policy inspection method showed insightful results and unveiled that the model could initiate therapy adequately and adjust therapy intensity to illness severity and disease progression which indicated safe and reliable model behaviour. Compared to current physician behavior, the developed policy prefers a more liberal use of vasopressors with a more restrained use of fluid therapy in line with previous work.Conclusion: We created a reinforcement learning model for optimal bedside hemodynamic management and demonstrated model transferability between populations from the USA and Europe for the first time. We proposed new methods for deep policy inspection integrating expert domain knowledge. This is expected to facilitate progression to bedside clinical decision support for the treatment of critically ill patients. [ABSTRACT FROM AUTHOR]

The goals of this study were to examine whether machine-learning algorithms outperform multivariable logistic regression in the prediction of insufficient response to methotrexate (MTX); secondly, to examine which features are essential for correct prediction; and finally, to investigate whether the best performing model specifically identifies insufficient responders to MTX (combination) therapy. The prediction of insufficient response (3-month Disease Activity Score 28-Erythrocyte-sedimentation rate (DAS28-ESR) > 3.2) was assessed using logistic regression, least absolute shrinkage and selection operator (LASSO), random forest, and extreme gradient boosting (XGBoost). The baseline features of 355 rheumatoid arthritis (RA) patients from the "treatment in the Rotterdam Early Arthritis CoHort" (tREACH) and the U-Act-Early trial were combined for analyses. The model performances were compared using area under the curve (AUC) of receiver operating characteristic (ROC) curves, 95% confidence intervals (95% CI), and sensitivity and specificity. Finally, the best performing model following feature selection was tested on 101 RA patients starting tocilizumab (TCZ)-monotherapy. Logistic regression (AUC = 0.77 95% CI: 0.68–0.86) performed as well as LASSO (AUC = 0.76, 95% CI: 0.67–0.85), random forest (AUC = 0.71, 95% CI: 0.61 = 0.81), and XGBoost (AUC = 0.70, 95% CI: 0.61–0.81), yet logistic regression reached the highest sensitivity (81%). The most important features were baseline DAS28 (components). For all algorithms, models with six features performed similarly to those with 16. When applied to the TCZ-monotherapy group, logistic regression's sensitivity significantly dropped from 83% to 69% (p = 0.03). In the current dataset, logistic regression performed equally well compared to machine-learning algorithms in the prediction of insufficient response to MTX. Models could be reduced to six features, which are more conducive for clinical implementation. Interestingly, the prediction model was specific to MTX (combination) therapy response. [ABSTRACT FROM AUTHOR]

A variety of effective psychotherapies for depression are available, but patients who suffer from depression vary in their treatment response. Combining face-to-face therapies with internet-based elements in the sense of blended treatment is a new approach to treatment for depression. The goal of this study was to answer the following research questions: (1) What are the most important predictors determining optimal treatment allocation to treatment as usual or blended treatment? and (2) Would model-determined treatment allocation using this predictive information and the personalized advantage index (PAI)-approach result in better treatment outcomes? Bayesian model averaging (BMA) was applied to the data of a randomized controlled trial (RCT) comparing the efficacy of treatment as usual and blended treatment in depressive outpatients. Pre-treatment symptomatology and treatment expectancy predicted outcomes irrespective of treatment condition, whereas different prescriptive predictors were found. A PAI of 2.33 PHQ-9 points was found, meaning that patients who would have received the treatment that is optimal for them would have had a post-treatment PHQ-9 score that is two points lower than if they had received the treatment that is suboptimal for them. For 29% of the sample, the PAI was five or greater, which means that a substantial difference between the two treatments was predicted. The use of the PAI approach for clinical practice must be further confirmed in prospective research; the current study supports the identification of specific interventions favorable for specific patients. [ABSTRACT FROM AUTHOR]