A cost-based multi-layer network approach for the discovery of patient phenotypes

Clinical records frequently include assessments of the characteristics of patients, which may include the completion of various questionnaires. These questionnaires provide a variety of perspectives on a patient's current state of well-being. Not only is it critical to capture the heterogeneity given by these perspectives, but there is also a growing demand for developing cost-effective technologies for clinical phenotyping. Filling out many questionnaires may be a strain for the patients and therefore costly. In this work, we propose COBALT -- a cost-based layer selector model for detecting phenotypes using a community detection approach. Our goal is to minimize the number of features used to build these phenotypes while preserving its quality. We test our model using questionnaire data from chronic tinnitus patients and represent the data in a multi-layer network structure. The model is then evaluated by predicting post-treatment data using baseline features (age, gender, and pre-treatment data) as well as the identified phenotypes as a feature. For some post-treatment variables, predictors using phenotypes from COBALT as features outperformed those using phenotypes detected by traditional clustering methods. Moreover, using phenotype data to predict post-treatment data proved beneficial in comparison with predictors that were solely trained with baseline features.Comment: 21 pages, 9 figures, submitted to JDS

Gender-Specific Differences in Patients With Chronic Tinnitus—Baseline Characteristics and Treatment Effects

Whilst some studies have identified gender-specific differences, there is no consensus about gender-specific determinants for prevalence rates or concomitant symptoms of chronic tinnitus such as depression or anxiety. However, gender-associated differences in psychological response profiles and coping strategies may differentially affect tinnitus chronification and treatment success rates. Thus, understanding gender-associated differences may facilitate a more detailed identification of symptom profiles, heighten treatment response rates, and help to create access for vulnerable populations that are potentially less visible in clinical settings. Our research questions are: RQ1: how do male and female tinnitus patients differ regarding tinnitus-related distress, depression severity, and treatment response, RQ2: to what extent are answers to questionnaires administered at baseline associated with gender, and RQ3: which baseline questionnaire items are associated with tinnitus distress, depression, and treatment response, while relating to one gender only? In this work, we present a data analysis workflow to investigate gender-specific differences in N = 1,628 patients with chronic tinnitus (828 female, 800male) who completed a 7-daymultimodal treatment encompassing cognitive behavioral therapy (CBT), physiotherapy, auditory attention training, and information counseling components. For this purpose, we extracted 181 variables from 7 self-report questionnaires on socio-demographics, tinnitus-related distress, tinnitus frequency, loudness, localization, and quality as well as physical and mental health status. Our workflow comprises (i) training machine learning models, (ii) a comprehensive evaluation including hyperparameter optimization, and (iii) post-learning steps to identify predictive variables. We found that female patients reported higher levels of tinnitus-related distress, depression and response to treatment (RQ1). Female patients indicated higher levels of tension, stress, and psychological coping strategies rates. By contrast, male patients reported higher levels of bodily pain associated with chronic tinnitus whilst judging their overall health as better (RQ2). Variables measuring depression, sleep problems, tinnitus frequency, and loudness were associated with tinnitus-related distress in both genders and indicators of mental health and subjective stress were found to be associated with depression in both genders (RQ3). Our results suggest that gender-associated differences in symptomatology and treatment response profiles suggest clinical and conceptual needs for differential diagnostics, case conceptualization and treatment pathways

Entity-level stream classification: exploiting entity similarity to label the future observations referring to an entity

Stream classification algorithms traditionally treat arriving instances as independent. However, in many applications, the arriving examples may depend on the “entity” that generated them, e.g. in product reviews 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 instances/“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, 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 from a domain/feature space different from that in which predictions are made. To distinguish between cases where this 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 m 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

Patient Empowerment through Summarization of Discussion Threads on Treatments in a Patient Self-Help Forum

Self-help patient fora are widely used for information acquisition and exchange of experiences, e.g., on the effects of medical treatments for a disease. However, a new patient may have difficulties in getting a fast overview of the information inside a large forum. We propose TinnitusTreatmentMonitor, a prototype tool for the summarization and sentiment characterization of postings on medical treatments. We report on applying TinnitusTreatmentMonitor on the platform TinnitusTalk1, a self-help platform for tinnitus patients

Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex

The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders

The statistical analysis plan for the unification of treatments and interventions for tinnitus patients randomized clinical trial (UNITI-RCT)

Background Tinnitus is a leading cause of disease burden globally. Several therapeutic strategies are recommended in guidelines for the reduction of tinnitus distress; however, little is known about the potentially increased effectiveness of a combination of treatments and personalized treatments for each tinnitus patient. Methods Within the Unification of Treatments and Interventions for Tinnitus Patients project, a multicenter, randomized clinical trial is conducted with the aim to compare the effectiveness of single treatments and combined treatments on tinnitus distress (UNITI-RCT). Five different tinnitus centers across Europe aim to treat chronic tinnitus patients with either cognitive behavioral therapy, sound therapy, structured counseling, or hearing aids alone, or with a combination of two of these treatments, resulting in four treatment arms with single treatment and six treatment arms with combinational treatment. This statistical analysis plan describes the statistical methods to be deployed in the UNITI-RCT. Discussion The UNITI-RCT trial will provide important evidence about whether a combination of treatments is superior to a single treatment alone in the management of chronic tinnitus patients. This pre-specified statistical analysis plan details the methodology for the analysis of the UNITI trial results. Trial registration ClinicalTrials.gov NCT04663828. The trial is ongoing. Date of registration: December 11, 2020. All patients that finished their treatment before 19 December 2022 are included in the main RCT analysis

Subpopulation Discovery in Epidemiological Data with Subspace Clustering

A prerequisite of personalized medicine is the identification of groups of people who share specific risk factors towards an outcome. We investigate the potential of subspace clustering for finding such groups in epidemiological data. We propose a workflow that encompasses clusterability assessment before cluster discovery and quality assessment after learning the clusters. Epidemiological usually do not have a ground truth for the verification of clusters found in subspaces. Hence, we introduce quality assessment through juxtaposition of the learned models to “models-of-randomness”, i.e. models that do not reflect a true cluster structure. On the basis of this workflow, we select subspace clustering methods, compare and discuss their performance. We use a dataset with hepatic steatosis as outcome, but our findings apply on arbitrary epidemiological cohort data that have tenths of variables and exhibit class skew