Project description:Classifying subjects into clinically and biologically homogeneous subgroups will facilitate the understanding of disease pathophysiology and development of targeted prevention and intervention strategies. Traditionally, disease subtyping is based on clinical characteristics alone, but subtypes identified by such an approach may not conform exactly to the underlying biological mechanisms. Very few studies have integrated genomic profiles (e.g., those from GWASs) with clinical symptoms for disease subtyping. Here we proposed an analytic framework capable of finding complex diseases subgroups by leveraging both GWAS-predicted gene expression levels and clinical data by a multi-view bicluster analysis. This approach connects SNPs to genes via their effects on expression, so the analysis is more biologically relevant and interpretable than a pure SNP-based analysis. Transcriptome of different tissues can also be readily modeled. We also proposed various evaluation metrics for assessing clustering performance. Our framework was able to subtype schizophrenia subjects into diverse subgroups with different prognosis and treatment response. We also applied the framework to the Northern Finland Birth Cohort (NFBC) 1966 dataset and identified high and low cardiometabolic risk subgroups in a gender-stratified analysis. The prediction strength by cross-validation was generally greater than 80%, suggesting good stability of the clustering model. Our results suggest a more data-driven and biologically informed approach to defining metabolic syndrome and subtyping psychiatric disorders. Moreover, we found that the genes "blindly" selected by the algorithm are significantly enriched for known susceptibility genes discovered in GWASs of schizophrenia or cardiovascular diseases. The proposed framework opens up an approach to subject stratification.
Project description:Importance:Catastrophizing is a maladaptive thought process that involves irrational fear and worry about anticipated or actual symptoms. Although clinically relevant, the role of catastrophizing in patients with chronic dizziness or imbalance has not yet been explored to our knowledge. Objectives:To validate a measure of dizziness catastrophizing and to assess its association with dizziness-related disability compared with other negative affect constructs (eg, anxiety and depression). Design, Setting, and Participants:For this retrospective medical record review, the Dizziness Catastrophizing Scale (DCS), a dizziness-specific catastrophizing assessment tool, was adapted from the previously validated Pain Catastrophizing Scale. Psychometric evaluation of the DCS was performed. In addition, the associations of dizziness catastrophizing and positive and negative affectivity with dizziness-related disability were assessed using structural equation modeling and regression analyses. Data were collected using a retrospective medical record review from April 27, 2010, to June 25, 2014. The dates of analysis were June 3 to August 15, 2017. The setting was the Multidisciplinary Neurotology Clinic at the Toronto General Hospital (Toronto, Ontario, Canada). Participants were 457 adult outpatients with dizziness or imbalance who were referred to the clinic. Main Outcomes and Measures:Psychometric properties of the DCS and its association with dizziness-related disability, as measured with the Dizziness Handicap Inventory. Results:Among 457 patients (mean [SD] age, 53.4 [15.4] years; 154 [33.7%] male), the DCS demonstrated good convergent (r = 0.78, P < .001) and discriminant validity (r = -0.40, P < .001) with the negative and positive affectivity, respectively; internal consistency (α = .95); and test-retest reliability (intraclass correlation coefficient, 0.92; P < .001 at the 95% CI). An exploratory dimension reduction analysis revealed a single latent component of the DCS. The results of the structural equation modeling and regression analyses revealed that dizziness catastrophizing, although associated with negative affectivity (eg, symptoms of anxiety and depression), was independently associated with dizziness-related disability (standardized β = 0.378; P < .001). Furthermore, a strong association was found between catastrophizing and dizziness-related disability across different dizziness-related diagnoses (r ≥ 0.6; P < .001). Conclusions and Relevance:In this study, the DCS was a valid and reliable measure for evaluating catastrophic thinking in patients with dizziness, which was independently associated with dizziness-related disability. Future studies should investigate the influence of alleviating symptoms of catastrophizing on functional outcomes in patients with dizziness or imbalance, the results of which will help guide novel approaches to the clinical care of patients with chronic dizziness.
Project description:Background: A cross-sectional observational study was designed to determine the impact of dizziness associated symptoms on the dizziness handicap inventory (DHI) in older adults (≥60 years). Methods: In total, 785 individuals referred to a multidisciplinary dizziness unit were assessed. Participants completed self-report questionnaires with general questions about symptoms of dizziness as well as the DHI. The DHI subscores (physical, functional, emotional) were calculated. Medical diagnoses were collected from the medical records of the patients. One-way MANOVA and networking analysis were used to analyze the impact of dizziness associated symptoms on dizziness handicap. Results: Most patients reported swaying dizziness (60.6%) and feeling of unsteadiness (59.8%) with substantial overlap between the types of dizziness. Most frequent dizziness associated symptoms were ear noise/tinnitus, visual problems, and nausea/vomiting. Network analysis revealed that visual disturbances, headache, and hearing impairment were associated with higher DHI and explained 12% of the DHI variance in the linear regression. In the one-way MANOVA visual problems and headache had an effect on all three DHI subscores, while hearing impairment was associated with the functional and emotional subscores of DHI. Conclusion: Distinct dizziness associated symptoms have substantial impact on dizziness handicap in older adults. A multifactorial assessment including these symptoms may assist in tailoring therapies to alleviate dizziness handicap in this group.
Project description:Background Dizziness is a common complaint in older adults. To know which factors are instrumental in enabling patients with chronic dizziness to tolerate their symptoms to a certain degree in everyday life can help to develop tailored therapies. Methods Data from 358 patients with chronic dizziness and vertigo who had attended a multimodal daycare treatment program were recorded. Data included sociodemographic parameters, dizziness-related characteristics, the Vertigo Symptom Scale (VSS), and the Hospital Anxiety and Depression Scale (HADS). Descriptive statistics, elastic net regression, and mediation analysis were used. Results A higher tolerance of dizziness was associated with higher age, higher intensity of dizziness, lower burden of dizziness, higher HADS depression, structural reason for dizziness (type), permanent dizziness, absence of attacks, and longer disease duration. In contrast, younger persons with attack-like dizziness reported to tolerate less dizziness. Age had a significant direct effect on tolerance (72% of the total effect) and a significant indirect effect via intensity on tolerance (28% of the total effect) in the mediation analysis. Conclusion It can only be speculated that negative stereotypes about age-related complaints may play a role in this. Why older people tolerate more dizziness and to what extent this may contribute to lower healthcare utilization need to be investigated in further studies.
Project description:BackgroundDizziness is a common symptom in adults, and chronic dizziness, such as persistent postural-perceptual dizziness, is also frequently reported and affects the quality of life of patients. This study aimed to identify psychosocial factors related to dizziness and chronic dizziness in a large-scale nationwide cohort.MethodsThis population-based cross-sectional study used the database of the Eighth Korea National Health and Nutrition Examination Survey in 2020. Data from 4,147 adults over 40 years old were analyzed, and 1,102 adults who experienced dizziness were included in the dizziness cohort. Demographic data, medical conditions, comorbidities, functional status variables, nutritional variables and psychological variables were collected. The pattern of depressive symptoms according to the severity of dizziness was analyzed by network analysis.ResultsThe prevalence rate of dizziness was 24.6% in the general population, and chronic dizziness (≥ 3 months) developed in 210 of 1,102 (17.1%) individuals who experienced dizziness. Multiple logistic regression analysis revealed that female sex, stress, and depression were associated with dizziness. Chronic dizziness was related to tympanic abnormalities, diabetes, short sleep duration, and higher levels of stress and depression. Psychomotor retardation/agitation was a central symptom of depression in patients with chronic dizziness.ConclusionsThis study found sex differences in factors associated with dizziness and identified psychosocial factors linked to chronic dizziness. Focusing on somatic factors rather than depressive symptoms may benefit patients with chronic dizziness.