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:Swift medically led scientifically informed responses to the Covid-19 epidemic nationally have been demonstrably superior to other, non-scientific approaches. In forensic psychiatry and across all psychiatric services, urgent and clinically led responses have underlined redundancies and confusions in the governance of mental health services and a vacuum in policy makers. For the future, a greater emphasis on services for patients with schizophrenia and other severe, enduring mental disorders must aim at reducing standardised mortality ratios, managing risk of violence and improving hard outcomes such as symptomatic remission, functional recovery and forensic recovery of autonomy. This will require more use of information technology at service level and at national level where Scandinavian-style population-based data linkage research must now become legally sanctioned and necessary. A national research and development centre for medical excellence in forensic psychiatry is urgently required and is complimentary to and different from quality management.