Provision and evaluation of explanations within an automated planning-based approach to solving the multimorbidity problem.

The multimorbidity problem involves the identification and mitigation of adverse interactions that occur when multiple computer interpretable guidelines are applied concurrently to develop a treatment plan for a patient diagnosed with multiple diseases. Solving this problem requires decision support approaches which are difficult to comprehend for physicians. As such, the rationale for treatment plans generated by these approaches needs to be provided. OBJECTIVE: To develop an explainability component for an automated planning-based approach to the multimorbidity problem, and to assess the fidelity and interpretability of generated explanations using a clinical case study. METHODS: The explainability component leverages the task-network model for representing computer interpretable guidelines. It generates post-hoc explanations composed of three aspects that answer why specific clinical actions are in a treatment plan, why specific revisions were applied, and how factors like medication cost, patient's adherence, etc. influence the selection of specific actions. The explainability component is implemented as part of MitPlan, where we revised our planning-based approach to support explainability. We developed an evaluation instrument based on the system causability scale and other vetted surveys to evaluate the fidelity and interpretability of its explanations using a two dimensional comparison study design. RESULTS: The explainability component was implemented for MitPlan and tested in the context of a clinical case study. The fidelity and interpretability of the generated explanations were assessed using a physician-focused evaluation study involving 21 participants from two different specialties and two levels of experience. Results show that explanations provided by the explainability component in MitPlan are of acceptable fidelity and interpretability, and that the clinical justification of the actions in a treatment plan is important to physicians. CONCLUSION: We created an explainability component that enriches an automated planning-based approach to solving the multimorbidity problem with meaningful explanations for actions in a treatment plan. This component relies on the task-network model to represent computer interpretable guidelines and as such can be ported to other approaches that also use the task-network model representation. Our evaluation study demonstrated that explanations that support a physician's understanding of the clinical reasons for the actions in a treatment plan are useful and important.

Using Unsupervised Machine Learning to Predict Quality of Life After Total Knee Arthroplasty.

BACKGROUND: Patient-reported outcome measures (PROMs) are an important metric to assess total knee arthroplasty (TKA) patients. The purpose of this study was to use a machine learning (ML) algorithm to identify patient features that impact PROMs after TKA. METHODS: Data from 636 TKA patients enrolled in our patient database between 2018 and 2022, were retrospectively reviewed. Their mean age was 68 years (range, 39 to 92), 56.7% women, and mean body mass index of 31.17 (range, 16 to 58). Patient demographics and the Functional Comorbidity Index were collected alongside Patient-Reported Outcome Measures Information System Global Health v1.2 (PROMIS GH-P) physical component scores preoperatively, at 3 months, and 1 year after TKA. An unsupervised ML algorithm (spectral clustering) was used to identify patient features impacting PROMIS GH-P scores at the various time points. RESULTS: The algorithm identified 5 patient clusters that varied by demographics, comorbidities, and pain scores. Each cluster was associated with predictable trends in PROMIS GH-P scores across the time points. Notably, patients who had the worst preoperative PROMIS GH-P scores (cluster 5) had the most improvement after TKA, whereas patients who had higher global health rating preoperatively had more modest improvement (clusters 1, 2, and 3). Two out of Five patient clusters (cluster 4 and 5) showed improvement in PROMIS GH-P scores that met a minimally clinically important difference at 1-year postoperative. CONCLUSIONS: The unsupervised ML algorithm identified patient clusters that had predictable changes in PROMs after TKA. It is a positive step toward providing precision medical care for each of our arthroplasty patients.

A community-of-practice-based evaluation methodology for knowledge intensive computational methods and its application to multimorbidity decision support.

OBJECTIVE: The study has dual objectives. Our first objective (1) is to develop a community-of-practice-based evaluation methodology for knowledge-intensive computational methods. We target a whitebox analysis of the computational methods to gain insight on their functional features and inner workings. In more detail, we aim to answer evaluation questions on (i) support offered by computational methods for functional features within the application domain; and (ii) in-depth characterizations of the underlying computational processes, models, data and knowledge of the computational methods. Our second objective (2) involves applying the evaluation methodology to answer questions (i) and (ii) for knowledge-intensive clinical decision support (CDS) methods, which operationalize clinical knowledge as computer interpretable guidelines (CIG); we focus on multimorbidity CIG-based clinical decision support (MGCDS) methods that target multimorbidity treatment plans. MATERIALS AND METHODS: Our methodology directly involves the research community of practice in (a) identifying functional features within the application domain; (b) defining exemplar case studies covering these features; and (c) solving the case studies using their developed computational methods-research groups detail their solutions and functional feature support in solution reports. Next, the study authors (d) perform a qualitative analysis of the solution reports, identifying and characterizing common themes (or dimensions) among the computational methods. This methodology is well suited to perform whitebox analysis, as it directly involves the respective developers in studying inner workings and feature support of computational methods. Moreover, the established evaluation parameters (e.g., features, case studies, themes) constitute a re-usable benchmark framework, which can be used to evaluate new computational methods as they are developed. We applied our community-of-practice-based evaluation methodology on MGCDS methods. RESULTS: Six research groups submitted comprehensive solution reports for the exemplar case studies. Solutions for two of these case studies were reported by all groups. We identified four evaluation dimensions: detection of adverse interactions, management strategy representation, implementation paradigms, and human-in-the-loop support. Based on our whitebox analysis, we present answers to the evaluation questions (i) and (ii) for MGCDS methods. DISCUSSION: The proposed evaluation methodology includes features of illuminative and comparison-based approaches; focusing on understanding rather than judging/scoring or identifying gaps in current methods. It involves answering evaluation questions with direct involvement of the research community of practice, who participate in setting up evaluation parameters and solving exemplar case studies. Our methodology was successfully applied to evaluate six MGCDS knowledge-intensive computational methods. We established that, while the evaluated methods provide a multifaceted set of solutions with different benefits and drawbacks, no single MGCDS method currently provides a comprehensive solution for MGCDS. CONCLUSION: We posit that our evaluation methodology, applied here to gain new insights into MGCDS, can be used to assess other types of knowledge-intensive computational methods and answer other types of evaluation questions. Our case studies can be accessed at our GitHub repository (https://github.com/william-vw/MGCDS).

Business school teams up with clinical innovators: An opportunity for health system transformation.

Healthcare represents one of the largest sectors in the economy with the health spending on average accounting for about 9% of GDP in OECD countries. Canada was projected in 2018 to spend about 11% of its GDP on healthcare with an expected health expenditure growth of 4.2%. Addressing this issue asks for a redesign of health delivery system and associated cultural shift allowing for incorporation of industry and business best practices. To make this redesign happen, system transformation requires seeking out new institutional mechanisms, partnerships, and forums where industry leaders in business and healthcare can develop a top-down approach with a shared vision, shared best practices, and support coming from a bottom-up approach through pilots and scaling-up initiatives. In this article, we describe one successful partnership initiative-Telfer Health Transformation Exchange at the Telfer School of Management at the University of Ottawa.

Ideating Mobile Health Behavioral Support for Compliance to Therapy for Patients with Chronic Disease: A Case Study of Atrial Fibrillation Management.

Poor patient compliance to therapy results in a worsening condition that often increases healthcare costs. In the MobiGuide project, we developed an evidence-based clinical decision-support system that delivered personalized reminders and recommendations to patients, helping to achieve higher therapy compliance. Yet compliance could still be improved and therefore building on the MobiGuide project experience, we designed a new component called the Motivational Patient Assistant (MPA) that is integrated within the MobiGuide architecture to further improve compliance. This component draws from psychological theories to provide behavioral support to improve patient engagement and thereby increasing patients' compliance. Behavior modification interventions are delivered via mobile technology at patients' home environments. Our approach was inspired by the IDEAS (Integrate, Design, Assess, and Share) framework for developing effective digital interventions to change health behavior; it goes beyond this approach by extending the Ideation phase' concepts into concrete backend architectural components and graphical user-interface designs that implement behavioral interventions. We describe in detail our ideation approach and how it was applied to design the user interface of MPA for anticoagulation therapy for the atrial fibrillation patients. We report results of a preliminary evaluation involving patients and care providers that shows the potential usefulness of the MPA for improving compliance to anticoagulation therapy.

Comprehensive mitigation framework for concurrent application of multiple clinical practice guidelines.

In this work we propose a comprehensive framework based on first-order logic (FOL) for mitigating (identifying and addressing) interactions between multiple clinical practice guidelines (CPGs) applied to a multi-morbid patient while also considering patient preferences related to the prescribed treatment. With this framework we respond to two fundamental challenges associated with clinical decision support: (1) concurrent application of multiple CPGs and (2) incorporation of patient preferences into the decision making process. We significantly expand our earlier research by (1) proposing a revised and improved mitigation-oriented representation of CPGs and secondary medical knowledge for addressing adverse interactions and incorporating patient preferences and (2) introducing a new mitigation algorithm. Specifically, actionable graphs representing CPGs allow for parallel and temporal activities (decisions and actions). Revision operators representing secondary medical knowledge support temporal interactions and complex revisions across multiple actionable graphs. The mitigation algorithm uses the actionable graphs, revision operators and available (and possibly incomplete) patient information represented in FOL. It relies on a depth-first search strategy to find a valid sequence of revisions and uses theorem proving and model finding techniques to identify applicable revision operators and to establish a management scenario for a given patient if one exists. The management scenario defines a safe (interaction-free) and preferred set of activities together with possible patient states. We illustrate the use of our framework with a clinical case study describing two patients who suffer from chronic kidney disease, hypertension, and atrial fibrillation, and who are managed according to CPGs for these diseases. While in this paper we are primarily concerned with the methodological aspects of mitigation, we also briefly discuss a high-level proof of concept implementation of the proposed framework in the form of a clinical decision support system (CDSS). The proposed mitigation CDSS "insulates" clinicians from the complexities of the FOL representations and provides semantically meaningful summaries of mitigation results. Ultimately we plan to implement the mitigation CDSS within our MET (Mobile Emergency Triage) decision support environment.

Using data envelopment analysis for assessing the performance of pediatric emergency department physicians.

In attempting to measure the performance of providers in a service industry such as health care, it is crucial that the measurement tool recognize both the efficiency and quality of service provided. We develop a Data Envelopment Analysis (DEA) model to help assess the performance of emergency department (ED) physicians at a partner hospital. The model incorporates efficiency measures as inputs and quality measures as outputs. We demonstrate the importance of a nuanced approach that recognizes the heterogeneity of patients that an ED physician encounters and the important role s/he plays as a mentor for physicians in training. In the study, patients were grouped according to their presenting complaint and ED physicians were assessed on each group separately. Performance variations were evident between physicians within each complaint group as well as between groups. A secondary grouping divided patients based on whether the attending physician was assisted by a trainee. Almost all ED physicians showed better performance scores when not assisted by trainees or ED fellows.

Using Semantic Components to Represent Dynamics of an Interdisciplinary Healthcare Team in a Multi-Agent Decision Support System.

In healthcare organizations, clinical workflows are executed by interdisciplinary healthcare teams (IHTs) that operate in ways that are difficult to manage. Responding to a need to support such teams, we designed and developed the MET4 multi-agent system that allows IHTs to manage patients according to presentation-specific clinical workflows. In this paper, we describe a significant extension of the MET4 system that allows for supporting rich team dynamics (understood as team formation, management and task-practitioner allocation), including selection and maintenance of the most responsible physician and more complex rules of selecting practitioners for the workflow tasks. In order to develop this extension, we introduced three semantic components: (1) a revised ontology describing concepts and relations pertinent to IHTs, workflows, and managed patients, (2) a set of behavioral rules describing the team dynamics, and (3) an instance base that stores facts corresponding to instances of concepts from the ontology and to relations between these instances. The semantic components are represented in first-order logic and they can be automatically processed using theorem proving and model finding techniques. We employ these techniques to find models that correspond to specific decisions controlling the dynamics of IHT. In the paper, we present the design of extended MET4 with a special focus on the new semantic components. We then describe its proof-of-concept implementation using the WADE multi-agent platform and the Z3 solver (theorem prover/model finder). We illustrate the main ideas discussed in the paper with a clinical scenario of an IHT managing a patient with chronic kidney disease.

Annealed fractional Lévy-Ito diffusion models for protein generation.

Protein generation has numerous applications in designing therapeutic antibodies and creating new drugs. Still, it is a demanding task due to the inherent complexities of protein structures and the limitations of current generative models. Proteins possess intricate geometry, and sampling their conformational space is challenging due to its high dimensionality. This paper introduces novel Markovian and non-Markovian generative diffusion models based on fractional stochastic differential equations and the Lévy distribution, allowing for a more effective exploration of the conformational space. The approach is applied to a dataset of 40,000 proteins and evaluated in terms of Fréchet distance, fidelity, and diversity, outperforming the state-of-the-art by 25.4%, 35.8%, and 11.8%, respectively.

Multivariable Prediction Models for Traumatic Spinal Cord Injury: A Systematic Review.

Background: Traumatic spinal cord injuries (TSCI) greatly affect the lives of patients and their families. Prognostication may improve treatment strategies, health care resource allocation, and counseling. Multivariable clinical prediction models (CPMs) for prognosis are tools that can estimate an absolute risk or probability that an outcome will occur. Objectives: We sought to systematically review the existing literature on CPMs for TSCI and critically examine the predictor selection methods used. Methods: We searched MEDLINE, PubMed, Embase, Scopus, and IEEE for English peer-reviewed studies and relevant references that developed multivariable CPMs to prognosticate patient-centered outcomes in adults with TSCI. Using narrative synthesis, we summarized the characteristics of the included studies and their CPMs, focusing on the predictor selection process. Results: We screened 663 titles and abstracts; of these, 21 full-text studies (2009-2020) consisting of 33 distinct CPMs were included. The data analysis domain was most commonly at a high risk of bias when assessed for methodological quality. Model presentation formats were inconsistently included with published CPMs; only two studies followed established guidelines for transparent reporting of multivariable prediction models. Authors frequently cited previous literature for their initial selection of predictors, and stepwise selection was the most frequent predictor selection method during modelling. Conclusion: Prediction modelling studies for TSCI serve clinicians who counsel patients, researchers aiming to risk-stratify participants for clinical trials, and patients coping with their injury. Poor methodological rigor in data analysis, inconsistent transparent reporting, and a lack of model presentation formats are vital areas for improvement in TSCI CPM research.

Mitigation of adverse interactions in pairs of clinical practice guidelines using constraint logic programming.

We propose a new method to mitigate (identify and address) adverse interactions (drug-drug or drug-disease) that occur when a patient with comorbid diseases is managed according to two concurrently applied clinical practice guidelines (CPGs). A lack of methods to facilitate the concurrent application of CPGs severely limits their use in clinical practice and the development of such methods is one of the grand challenges for clinical decision support. The proposed method responds to this challenge. We introduce and formally define logical models of CPGs and other related concepts, and develop the mitigation algorithm that operates on these concepts. In the algorithm we combine domain knowledge encoded as interaction and revision operators using the constraint logic programming (CLP) paradigm. The operators characterize adverse interactions and describe revisions to logical models required to address these interactions, while CLP allows us to efficiently solve the logical models - a solution represents a feasible therapy that may be safely applied to a patient. The mitigation algorithm accepts two CPGs and available (likely incomplete) patient information. It reports whether mitigation has been successful or not, and on success it gives a feasible therapy and points at identified interactions (if any) together with the revisions that address them. Thus, we consider the mitigation algorithm as an alerting tool to support a physician in the concurrent application of CPGs that can be implemented as a component of a clinical decision support system. We illustrate our method in the context of two clinical scenarios involving a patient with duodenal ulcer who experiences an episode of transient ischemic attack.

Using graph rewriting to operationalize medical knowledge for the revision of concurrently applied clinical practice guidelines.

Clinical practice guidelines (CPGs) are patient management tools that synthesize medical knowledge into an actionable format. CPGs are disease specific with limited applicability to the management of complex patients suffering from multimorbidity. For the management of these patients, CPGs need to be augmented with secondary medical knowledge coming from a variety of knowledge repositories. The operationalization of this knowledge is key to increasing CPGs' uptake in clinical practice. In this work, we propose an approach to operationalizing secondary medical knowledge inspired by graph rewriting. We assume that the CPGs can be represented as task network models, and provide an approach for representing and applying codified medical knowledge to a specific patient encounter. We formally define revisions that model and mitigate adverse interactions between CPGs and we use a vocabulary of terms to instantiate these revisions. We demonstrate the application of our approach using synthetic and clinical examples. We conclude by identifying areas for future work with the vision of developing a theory of mitigation that will facilitate the development of comprehensive decision support for the management of multimorbid patients.

ProtInteract: A deep learning framework for predicting protein-protein interactions.

Proteins mainly perform their functions by interacting with other proteins. Protein-protein interactions underpin various biological activities such as metabolic cycles, signal transduction, and immune response. However, due to the sheer number of proteins, experimental methods for finding interacting and non-interacting protein pairs are time-consuming and costly. We therefore developed the ProtInteract framework to predict protein-protein interaction. ProtInteract comprises two components: first, a novel autoencoder architecture that encodes each protein's primary structure to a lower-dimensional vector while preserving its underlying sequence attributes. This leads to faster training of the second network, a deep convolutional neural network (CNN) that receives encoded proteins and predicts their interaction under three different scenarios. In each scenario, the deep CNN predicts the class of a given encoded protein pair. Each class indicates different ranges of confidence scores corresponding to the probability of whether a predicted interaction occurs or not. The proposed framework features significantly low computational complexity and relatively fast response. The contributions of this work are twofold. First, ProtInteract assimilates the protein's primary structure into a pseudo-time series. Therefore, we leverage the nature of the time series of proteins and their physicochemical properties to encode a protein's amino acid sequence into a lower-dimensional vector space. This approach enables extracting highly informative sequence attributes while reducing computational complexity. Second, the ProtInteract framework utilises this information to identify protein interactions with other proteins based on its amino acid configuration. Our results suggest that the proposed framework performs with high accuracy and efficiency in predicting protein-protein interactions.

Why did AI get this one wrong? - Tree-based explanations of machine learning model predictions.

Increasingly complex learning methods such as boosting, bagging and deep learning have made ML models more accurate, but harder to interpret and explain, culminating in black-box machine learning models. Model developers and users alike are often presented with a trade-off between performance and intelligibility, especially in high-stakes applications like medicine. In the present article we propose a novel methodological approach for generating explanations for the predictions of a generic machine learning model, given a specific instance for which the prediction has been made. The method, named AraucanaXAI, is based on surrogate, locally-fitted classification and regression trees that are used to provide post-hoc explanations of the prediction of a generic machine learning model. Advantages of the proposed XAI approach include superior fidelity to the original model, ability to deal with non-linear decision boundaries, and native support to both classification and regression problems. We provide a packaged, open-source implementation of the AraucanaXAI method and evaluate its behaviour in a number of different settings that are commonly encountered in medical applications of AI. These include potential disagreement between the model prediction and physician's expert opinion and low reliability of the prediction due to data scarcity.

A data-driven approach to categorize patients with traumatic spinal cord injury: cluster analysis of a multicentre database.

Background: Conducting clinical trials for traumatic spinal cord injury (tSCI) presents challenges due to patient heterogeneity. Identifying clinically similar subgroups using patient demographics and baseline injury characteristics could lead to better patient-centered care and integrated care delivery. Purpose: We sought to (1) apply an unsupervised machine learning approach of cluster analysis to identify subgroups of tSCI patients using patient demographics and injury characteristics at baseline, (2) to find clinical similarity within subgroups using etiological variables and outcome variables, and (3) to create multi-dimensional labels for categorizing patients. Study design: Retrospective analysis using prospectively collected data from a large national multicenter SCI registry. Methods: A method of spectral clustering was used to identify patient subgroups based on the following baseline variables collected since admission until rehabilitation: location of the injury, severity of the injury, Functional Independence Measure (FIM) motor, and demographic data (age, and body mass index). The FIM motor score, the FIM motor score change, and the total length of stay were assessed on the subgroups as outcome variables at discharge to establish the clinical similarity of the patients within derived subgroups. Furthermore, we discussed the relevance of the identified subgroups based on the etiological variables (energy and mechanism of injury) and compared them with the literature. Our study also employed a qualitative approach to systematically describe the identified subgroups, crafting multi-dimensional labels to highlight distinguishing factors and patient-focused insights. Results: Data on 334 tSCI patients from the Rick Hansen Spinal Cord Injury Registry was analyzed. Five significantly different subgroups were identified (p-value ≤0.05) based on baseline variables. Outcome variables at discharge superimposed on these subgroups had statistically different values between them (p-value ≤0.05) and supported the notion of clinical similarity of patients within each subgroup. Conclusion: Utilizing cluster analysis, we identified five clinically similar subgroups of tSCI patients at baseline, yielding statistically significant inter-group differences in clinical outcomes. These subgroups offer a novel, data-driven categorization of tSCI patients which aligns with their demographics and injury characteristics. As it also correlates with traditional tSCI classifications, this categorization could lead to improved personalized patient-centered care.

Developing a pneumonia diagnosis ontology from multiple knowledge sources.

Background: Pneumonia is difficult to differentiate from other pulmonary diseases because it shares many symptoms with these diseases. Diagnosing pneumonia in clinical practice would benefit from having access to a codified representation of clinical knowledge. An ontology represents a well-established paradigm for such codification. Objectives: The goal of this research is to create Pneumonia Diagnosis Ontology (PNADO) that brings together the medical knowledge dispersed among multiple medical knowledge sources. Material and Methods: We used several clinical practice guidelines (CPGs) describing the pneumonia diagnostic process as a starting point in developing PNADO. Preliminary version of PNADO was subsequently expanded to cover a broader range of the concepts by reusing ontologies from Open Biological and Biomedical Ontology (OBO) Foundry and BioPortal. PNADO was evaluated by examining relevant concepts from the pneumonia-specific systematic reviews, using patient data from the MIMIC-III clinical dataset, and by clinical domain experts. Results: PNADO is a comprehensive ontology and has a rich set of classes and properties that cover different types of pneumonia, pathogens, symptoms, clinical signs, laboratory tests and imaging, clinical findings, complications, and diagnoses. Conclusion: PNADO unifies pneumonia diagnostic concepts from multiple knowledge sources. It is available in the BioPortal repository.

Protein-protein interaction prediction with deep learning: A comprehensive review.

Most proteins perform their biological function by interacting with themselves or other molecules. Thus, one may obtain biological insights into protein functions, disease prevalence, and therapy development by identifying protein-protein interactions (PPI). However, finding the interacting and non-interacting protein pairs through experimental approaches is labour-intensive and time-consuming, owing to the variety of proteins. Hence, protein-protein interaction and protein-ligand binding problems have drawn attention in the fields of bioinformatics and computer-aided drug discovery. Deep learning methods paved the way for scientists to predict the 3-D structure of proteins from genomes, predict the functions and attributes of a protein, and modify and design new proteins to provide desired functions. This review focuses on recent deep learning methods applied to problems including predicting protein functions, protein-protein interaction and their sites, protein-ligand binding, and protein design.

A scoping review of complication prediction models in spinal surgery: An analysis of model development, validation and impact.

Background: Predictive analytics are being used increasingly in the field of spinal surgery with the development of models to predict post-surgical complications. Predictive models should be valid, generalizable, and clinically useful. The purpose of this review was to identify existing post-surgical complication prediction models for spinal surgery and to determine if these models are being adequately investigated with internal/external validation, model updating and model impact studies. Methods: This was a scoping review of studies pertaining to models for the prediction of post-surgical complication after spinal surgery published over 10 years (2010-2020). Qualitative data was extracted from the studies to include study classification, adherence to Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) guidelines and risk of bias (ROB) assessment using the Prediction model study Risk Of Bias Assessment Tool (PROBAST). Model evaluation was determined using area under the curve (AUC) when available. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement was used as a basis for the search methodology in four different databases. Results: Thirty studies were included in the scoping review and 80% (24/30) included model development with or without internal validation. Twenty percent (6/30) were exclusively external validation studies and only one study included an impact analysis in addition to model development and internal validation. Two studies referenced the TRIPOD guidelines and there was a high ROB in 100% of the studies using the PROBAST tool. Conclusions: The majority of post-surgical complication prediction models in spinal surgery have not undergone standardized model development and internal validation or adequate external validation and impact evaluation. As such there is uncertainty as to their validity, generalizability, and clinical utility. Future efforts should be made to use existing tools to ensure standardization in development and rigorous evaluation of prediction models in spinal surgery.

MitPlan: A planning approach to mitigating concurrently applied clinical practice guidelines.

As the population ages, patients' complexity and the scope of their care is increasing. Over 60% of the population is 65 years of age or older and suffers from multi-morbidity, which is associated with two times as many patient-physician encounters. Yet clinical practice guidelines (CPGs) are developed to treat a single disease. To reconcile these two competing issues, previously we developed a framework for mitigation, i.e., identifying and addressing adverse interactions in multi-morbid patients managed according to multiple CPGs. That framework relies on first-order logic (FOL) to represent CPGs and secondary medical knowledge and FOL theorem proving to establish valid patient management plans. In the work presented here, we leverage our earlier research and simplify the mitigation process by representing it as a planning problem using the Planning Domain Definition Language (PDDL). This new framework, called MitPlan, identifies and addresses adverse interactions using durative planning actions that embody clinical actions (including medication administration and patient testing), supports a physician-defined length of planning horizons, and optimizes plans based on patient preferences and action costs. It supports a variety of criteria when developing management plans, including the total cost of prescribed treatment and the cost of the revisions to be introduced. The solution to MitPlan's planning problem is a sequence of timed actions that are easy to interpret when creating a management plan. We demonstrate MitPlan's capabilities using illustrative and clinical case studies.

A Health eLearning Ontology and Procedural Reasoning Approach for Developing Personalized Courses to Teach Patients about Their Medical Condition and Treatment.

We propose a methodological framework to support the development of personalized courses that improve patients' understanding of their condition and prescribed treatment. Inspired by Intelligent Tutoring Systems (ITSs), the framework uses an eLearning ontology to express domain and learner models and to create a course. We combine the ontology with a procedural reasoning approach and precompiled plans to operationalize a design across disease conditions. The resulting courses generated by the framework are personalized across four patient axes-condition and treatment, comprehension level, learning style based on the VARK (Visual, Aural, Read/write, Kinesthetic) presentation model, and the level of understanding of specific course content according to Bloom's taxonomy. Customizing educational materials along these learning axes stimulates and sustains patients' attention when learning about their conditions or treatment options. Our proposed framework creates a personalized course that prepares patients for their meetings with specialists and educates them about their prescribed treatment. We posit that the improvement in patients' understanding of prescribed care will result in better outcomes and we validate that the constructs of our framework are appropriate for representing content and deriving personalized courses for two use cases: anticoagulation treatment of an atrial fibrillation patient and lower back pain management to treat a lumbar degenerative disc condition. We conduct a mostly qualitative study supported by a quantitative questionnaire to investigate the acceptability of the framework among the target patient population and medical practitioners.