BACKGROUND: Current clinical decision support systems (DSS) are trained and validated on observational data from the clinic in which the DSS is going to be applied. This is problematic for treatments that have already been validated in a randomized clinical trial (RCT), but have not yet been introduced in any clinic. In this work, we report on a method for training and validating the DSS core before introduction to a clinic, using the RCT data themselves. The key challenges we address are of missingness, foremost: missing rationale when assigning a treatment to a patient (the assignment is at random), and missing verification evidence, since the effectiveness of a treatment for a patient can only be verified (ground truth) if the treatment was indeed assigned to the patient - but then the assignment was at random. MATERIALS: We use the data of a multi-armed clinical trial that investigated the effectiveness of single treatments and combination treatments for 240+ tinnitus patients recruited and treated in 5 clinical centres. METHODS: To deal with the 'missing rationale for treatment assignment' challenge, we re-model the target variable that measures the outcome of interest, in order to suppress the effect of the individual treatment, which was at random, and control on the effect of treatment in general. To deal with missing features for many patients, we use a learning core that is robust to missing features. Further, we build ensembles that parsimoniously exploit the small patient numbers we have for learning. To deal with the 'missing verification evidence' challenge, we introduce counterfactual treatment verification, a verification scheme that juxtaposes the effectiveness of the recommendations of our approach to the effectiveness of the RCT assignments in the cases of agreement/disagreement between the two. RESULTS AND LIMITATIONS: We demonstrate that our approach leverages the RCT data for learning and verification, by showing that the DSS suggests treatments that improve the outcome. The results are limited through the small number of patients per treatment; while our ensemble is designed to mitigate this effect, the predictive performance of the methods is affected by the smallness of the data. OUTLOOK: We provide a basis for the establishment of decision supporting routines on treatments that have been tested in RCTs but have not yet been deployed clinically. Practitioners can use our approach to train and validate a DSS on new treatments by simply using the RCT data available to them. More work is needed to strengthen the robustness of the predictors. Since there are no further data available to this purpose, but those already used, the potential of synthetic data generation seems an appropriate alternative.

We present the framework GUCCI (Guided Cardiac Cohort Investigation), which provides a guided visual analytics workflow to analyze cohort-based measured blood flow data in the aorta. In the past, many specialized techniques have been developed for the visual exploration of such data sets for a better understanding of the influence of morphological and hemodynamic conditions on cardiovascular diseases. However, there is a lack of dedicated techniques that allow visual comparison of multiple data sets and defined cohorts, which is essential to characterize pathologies. GUCCI offers visual analytics techniques and novel visualization methods to guide the user through the comparison of predefined cohorts, such as healthy volunteers and patients with a pathologically altered aorta. The combination of overview and glyph-based depictions together with statistical cohort-specific information allows investigating differences and similarities of the time-dependent data. Our framework was evaluated in a qualitative user study with three radiologists specialized in cardiac imaging and two experts in medical blood flow visualization. They were able to discover cohort-specific characteristics, which supports the derivation of standard values as well as the assessment of pathology-related severity and the need for treatment.

An accurate assessment of the cardiovascular system and prediction of cardiovascular diseases (CVDs) are crucial. Cardiac blood flow data provide insights about patient-specific hemodynamics. However, there is a lack of machine learning approaches for a feature-based classification of heart-healthy people and patients with CVDs. In this paper, we investigate the potential of morphological and hemodynamic features extracted from measured blood flow data in the aorta to classify heart-healthy volunteers (HHV) and patients with bicuspid aortic valve (BAV). Furthermore, we determine features that distinguish male vs. female patients and elderly HHV vs. BAV patients. We propose a data analysis pipeline for cardiac status classification, encompassing feature selection, model training, and hyperparameter tuning. Our results suggest substantial differences in flow features of the aorta between HHV and BAV patients. The excellent performance of the classifiers separating between elderly HHV and BAV patients indicates that aging is not associated with pathological morphology and hemodynamics. Our models represent a first step towards automated diagnosis of CVS using interpretable machine learning models.

Electronic health records (EHR) often include multiple perspectives on a patient's current state of well-being (e.g. vital signs and subjective indicators measured by questionnaires). In this study, we use these perspectives to build phenotypes of chronic tinnitus patients and investigate how these phenotypes are associated with response to treatment. Therefore, we model patients as nodes in a network, where those perspectives are interpreted as layers of a multi-layer network. To identify phenotypes of patients in the network, we implement a community detection algorithm. Some of these communities can be considered as phenotypes if they represent subgroups of patients that are similar according to the investigated perspectives. Furthermore, we analyze the influence of the layers on the final community structure of patients. We then propose a method to add layers given their community structure similarity. Finally, we fit a model, per community, to predict the treatment outcome. In some communities, this prediction outperformed the baseline scenario where the predictor was fitted to all patients.

Abstract Attrition or dropout is the most severe missingness problem in longitudinal cohort study data where some participants do not show up for follow‐up examinations. Dropouts result in biased data and cause the reduction of 1ata set size. Moreover, they limit the power of statistical analysis and the validity of study findings. Visualization can play a strong role in analysing and displaying the missingness patterns. In this work, we present VIVID, a framework for the visual analysis of missing values in cohort study data. VIVID is inspired by discussions with epidemiologists and adds visual components to their current statistics‐based approaches. VIVID provides functions for exploration, imputation and validity check of imputations. The main focus of this paper is multiple imputation to fix the missing data.

Epidemiological population-based studies collect hundreds of socio-demographic, lifestyle-related, and health related variables for thousands of individuals in order to better characterize health and disease in a defined population. To understand the relations between the variables in the study data, we employ Bayesian Networks, as they not only represent associations between variables but also assign probabilities to these associations. The probabilistic associations allow us to draw inference for unknown events in question, based on the provided evidence. In our work, we induce a Bayesian Network from the data of the population-based epidemiological Study of Health in Pomerania (SHIP), to identify variables related to the outcome "fatty liver". We report on Bayesian Network structure learning, identification of variables associated with the outcome, and the strong associations identified among the variables.

Intracranial aneurysms are pathologic dilations of the vessel wall, which bear the risk of rupture and of fatal consequences for the patient. Since treatment may be accompanied by severe complications as well, rupture risk assessment and thus rupture risk prediction plays an important role in clinical research. In this work, we investigate the potential of morphological features for rupture risk status classification in 100 intracranial aneurysms. We propose a pipeline for morphological feature extraction and rupture status classification with subsequent feature ranking and inspection. Our classification setup involves training separate models for each aneurysm type (sidewall or bifurcation) with multiple learning algorithms. We report on the classification performance of our pipeline and examine the predictive power of each morphological parameter towards rupture status classification. Further, we identify the most important features for the best models and study their marginal prediction.

Diabetic foot syndrome is a frequent and serious complication occurring among patients with diabetes. In this study, we investigate the potential of intelligent wearables that monitor temperature changes of the foot surface through temperature sensors. In particular, we are interested in identifying differences between the temperature variations recorded on patients with the disorder and healthy people during an experiment. To this purpose, we propose a method that encompasses shapelet-based timeseries classification and shapelet ranking on predictiveness. We report on our results for an experiment consisting of stance and rest periods of increasing duration.

Stream classification algorithms traditionally treat arriving observations as independent. However, in many applications the arriving examples may depend on the "entity" that generated them, e.g. in product reviewing or in the interactions of users with an application server. In this study, we investigate the potential of this dependency by partitioning the original stream of observations into entity-centric substreams and by incorporating entity-specific information into the learning model. We propose a k Nearest Neighbour inspired stream classification approach (kNN), in which the label of an arriving observation is predicted by exploiting knowledge on the observations belonging to this entity and to entities similar to it. For the computation of entity similarity, we consider knowledge about the observations and knowledge about the entity, potentially transferred from another domain. To distinguish between cases where this kind of knowledge transfer is beneficial for stream classification and cases where the knowledge on the entities does not contribute to classifying the observations, we also propose a heuristic approach based on random sampling of substreams using k Random Entities (kRE). Our learning scenario is not fully supervised: after acquiring labels for the initial few observations of each entity, we assume that no additional labels arrive, and attempt to predict the labels of near-future and far-future observations from that initial seed. We report on our findings from three datasets.

Subgroup discovery (SD) exploits its full value in applications where the goal is to generate understandable models. Epidemiologists search for statistically significant relationships between risk factors and outcome in large and heterogeneous datasets encompassing information about the participants health status gathered from questionnaires, medical examinations and image acquisition. SD algorithms can help epidemiologists by automatically detecting such relationships presented as comprehensible rules, aiming to ultimately improve prevention, diagnosis and treatment of diseases. However, SD algorithms often produce large and overlapping rule sets requiring the expert to conduct a manual post-filtering step that is time-consuming and tedious. In this work, we propose a clustering-based algorithm that hierarchically reorganizes rule sets and summarizes all important concepts while maintaining diversity between the rule clusters. For each cluster, a representative rule is selected and then displayed to the expert who in turn can drill-down to other cluster members. We evaluate our algorithm on two cohort study datasets where the diseases hepatic steatosis and goiter serve as target variable, respectively. We report on our findings with respect to effectiveness of our algorithm and we present selected subpopulations.

Personalized medicine benefits from the identification of subpopulations that exhibit higher prevalence of a disease than the general population: such subpopulations can become the target of more intensive investigations to identify risk factors and to develop dedicated therapies. Classification rule discovery algorithms are an appropriate tool for discovering such subpopulations: they scale well, even for multi-dimensional data and deliver comprehensible patterns. However, they may generate hundreds of rules and thus call for exploration methods. In this study, we extend the tool Interactive Medical Miner for the discovery of classification rules, into the Interactive Classification rule Explorer ICE, which offers functionalities for rule exploration, grouping, rule visualization and statistics. We report on our first results for the classification of cohort data on goiter, a disorder of the thyroid gland.

The diabetic foot syndrome (DFS) is linked to loss of neuron functions, implying that the patients do not feel their feet and may unknowingly injure themselves or apply excessive plantar pressure. Such patients are at 17-40 times higher risk of foot amputation than non-diabetics. Sensor-equipped insoles are being developed to warn diabetics against inadverted excessive pressure. For the successful use of such technology, it is essential to understand how patients distribute plantar pressure load and to identify common pressure patterns, to be later used as basis for recognizing abnormalities. In this study, we propose a mining workflow for the discovery of pressure patterns among DFS patients. Our approach encompasses different ways of modeling pressure distribution among foot regions, and workpaths for the computation of similarity between patients and the construction of clusters of patients who apply pressure on their feet the same way. We report on our findings from a dataset of experiment participants who wore sensor-equipped insoles and were asked to apply and release pressure repeatedly over a time period of several minutes. We elaborate on the pressure patterns thus identified and juxtapose them to findings from the literature.

Epidemiological studies comprise heterogeneous data about a subject group to define disease-specific risk factors. These data contain information (features) about a subject's lifestyle, medical status as well as medical image data. Statistical regression analysis is used to evaluate these features and to identify feature combinations indicating a disease (the target feature). We propose an analysis approach of epidemiological data sets by incorporating all features in an exhaustive regression-based analysis. This approach combines all independent features w.r.t. a target feature. It provides a visualization that reveals insights into the data by highlighting relationships. The 3D Regression Heat Map, a novel 3D visual encoding, acts as an overview of the whole data set. It shows all combinations of two to three independent features with a specific target disease. Slicing through the 3D Regression Heat Map allows for the detailed analysis of the underlying relationships. Expert knowledge about disease-specific hypotheses can be included into the analysis by adjusting the regression model formulas. Furthermore, the influences of features can be assessed using a difference view comparing different calculation results. We applied our 3D Regression Heat Map method to a hepatic steatosis data set to reproduce results from a data mining-driven analysis. A qualitative analysis was conducted on a breast density data set. We were able to derive new hypotheses about relations between breast density and breast lesions with breast cancer. With the 3D Regression Heat Map, we present a visual overview of epidemiological data that allows for the first time an interactive regression-based analysis of large feature sets with respect to a disease.

Medical research can greatly benefit from advances in data mining. We propose a mining approach for cohort analysis in a longitudinal population-based epidemiological study, and show that modelling and exploiting the evolution of cohort participants over time improves classification quality towards an outcome (a disease). Our mining workflow encompasses steps for tracing the evolution of the cohort participants and for using evolution features in classification. We show that our approach separates better between classes and that change in the values of variables is predictive. We report on results for the liver disorder hepatic steatosis (high fat accumulation in the liver), but our approach is appropriate for classification of longitudinal epidemiological data on further disorders.

We investigate the task of breast tumor classification based on dynamic contrast-enhanced magnetic resonance image data (DCE-MRI). Our objective is to study how the formation of regions of similar voxels contributes to distinguishing between benign and malignant tumors. First, we perform clustering on each tumor with different algorithms and parameter settings, and then combine the clustering results to identify the most suspect region of the tumor and derive features from it. With these features we train classifiers on a set of tumors that are difficult to classify, even for human experts. We show that the features of the most suspect region alone cannot distinguish between benign and malignant tumors, yet the properties of this region are indicative of tumor malignancy for the dataset we studied.