Dataset Information

Measuring Health-Related Quality of Life in Tuberous Sclerosis Complex - Psychometric Evaluation of Three Instruments in Individuals With Refractory Epilepsy.

ABSTRACT: Tuberous sclerosis complex (TSC) is a rare genetic disease associated with significant disease burden and considerable impact on health-related quality of life (HRQL). Currently no disease-specific clinical outcome assessments evaluate HRQL in individuals with TSC. A multi-center phase III study EXIST-3 (NCT01713946) assessed the efficacy and safety of two trough exposure ranges (Low exposure, LE: 3-7 ng/mL and high exposure, HE: 9-15 ng/mL) of adjunctive everolimus in patients aged 2-65 years with TSC and refractory partial-onset seizures (N = 366). Three age-specific HRQL measures were included as secondary endpoints including: quality of life in childhood epilepsy (QOLCE; caregiver-report for aged 2- < 11), the Quality of Life in Epilepsy Inventory for Adolescents-48 (QOLIE-AD-48; self-report, aged ? 11- < 18), and the Quality of Life in Epilepsy Inventory-31-Problems (QOLIE-31-P; self-report, aged ? 18). Intellectual ability was evaluated using the Wechsler Non-Verbal (WNV) Scale of Ability. Post hoc analyses were performed on the core phase primary data from EXIST-3 to evaluate the psychometric properties of the HRQL measures and calculate meaningful change estimates. Results showed that a significant subset of the trial sample (4-21 year olds) scored in the intellectual disability range, as assessed by the WNV. Psychometric analyses of the three epilepsy measures (including reliability, validity, and ability to detect change) supported the appropriateness for use in TSC. Distribution-based meaningful change estimates were generated for each HRQL measure, with estimates for the QOLIE-31-P total score largely consistent with the published literature. To our knowledge, this is the first evaluation using clinical trial data to establish the psychometric properties of the QOLCE, QOLIE-AD-48, and QOLIE-31-P for use in individuals with TSC. These findings increase confidence in the measures as valid and reliable for use in clinical trials and future research in patients with TSC.

SUBMITTER: de Vries PJ

PROVIDER: S-EPMC6126421 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Measuring Health-Related Quality of Life in Tuberous Sclerosis Complex - Psychometric Evaluation of Three Instruments in Individuals With Refractory Epilepsy.

de Vries Petrus J PJ Franz David N DN Curatolo Paolo P Nabbout Rima R Neary Maureen M Herbst Fabian F Sully Kate K Brohan Elaine E Bennett Bryan B Lawson John A JA

Frontiers in pharmacology 20180830

Tuberous sclerosis complex (TSC) is a rare genetic disease associated with significant disease burden and considerable impact on health-related quality of life (HRQL). Currently no disease-specific clinical outcome assessments evaluate HRQL in individuals with TSC. A multi-center phase III study EXIST-3 (NCT01713946) assessed the efficacy and safety of two trough exposure ranges (Low exposure, LE: 3-7 ng/mL and high exposure, HE: 9-15 ng/mL) of adjunctive everolimus in patients aged 2-65 years w ...[more]

PMID: 30214408

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Project description:Objective:To estimate health-related quality of life (HRQoL) in patients with tuberous sclerosis complex (TSC) and associated manifestations and to identify potential factors associated with HRQoL in this population of patients. Methods:We performed a retrospective chart review of adults with TSC who attended the outpatient clinic of the University Medical Center Utrecht in the Netherlands from 1990 to 2015 (N = 363; on average 33.6 years of follow-up). HRQoL data were assessed in 2012 using the Health Utility Index version 3 (HUI-3) questionnaire completed by patients or caregivers (N = 214 with HUI score and ?1 TSC manifestation, including renal angiomyolipomas [rAMLs], subependymal giant cell astrocytoma [SEGA], or epilepsy). Results:Of 214 patients in the study sample, 171 had TSC-associated epilepsy (with or without rAML/SEGA), 37 had TSC and rAML (without epilepsy or SEGA), and 6 had other combinations of manifestations. The median HUI score for the 214 patients with ?1 TSC manifestation was 0.51 (-0.371 to 1 scale, 1 = perfect health, 0 = death, <0 = worse than death). Among all components used to build the overall HUI score, the cognition component had the lowest score (mean = 0.47; 0-1 scale). Patients with TSC-epilepsy had significantly lower overall HUI than patients with TSC and rAML only (median HUI = 0.31 vs 0.95, P < .05), especially those who were in refractory state for prolonged periods of time (median HUI = -0.11 among patients with seizures during the entire duration of their follow-up time). In multivariate analyses, severe impairment of daily functioning was the strongest predictor of HRQoL decrement (adjusted HUI difference between patients with severe vs. no impairment = -0.55, P < .05). Significance:This study showed that TSC-related epilepsy is associated with lower HUI, especially for patients who have refractory seizures for prolonged periods of time. Early and effective interventions to control or reduce seizures and preserve patients' cognitive functions may help to improve patients' quality of life.

Project description:BackgroundCoaching is emerging as a novel approach to guide medical students toward becoming competent, reflective physicians and master adaptive learners. However, no instruments currently exist to measure academic coaching at the undergraduate medical education level.ObjectiveTo describe the development and psychometric assessments of two instruments designed to assess academic coaching of medical students toward creating a robust measurement model of this educational paradigm.DesignObservational psychometric.ParticipantsAll medical students in the 2014 and 2015 cohorts and all their coaches were invited to complete the instruments being tested, which led to 662 medical student responses from 292 medical students and 468 coaching responses from 22 coaches being included in analyses. Medical student response rates were 75.7% from 2014 and 75.5% from 2015. Overall, the coaches' response rate was 71%.Main measuresTwo 31-item instruments were initially developed, one for medical students to assess their coach and one for faculty coaches to assess their students, both of which evaluated coaching based on definitions we formulated using existing literature. Each was administered to two cohorts of medical students and coaches in 2015 and 2016. An exploratory factor analysis using principal component analysis as the extraction method and Varimax with Kaiser normalization as the rotation method was conducted.Key resultsEighteen items reflecting four domains were retained with eigenvalues higher than 1.0 for medical students' assessment of coaching, which measured promoting self-monitoring, relationship building, promoting reflective behavior, and establishing foundational ground rules. Sixteen items reflecting two domains were retained for the faculty assessment of coaching with eigenvalues higher than 1.0: the Practice of Coaching and Relationship Formation.ConclusionsWe successfully developed and psychometrically validated surveys designed to measure key aspects of the coaching relationship, coaching processes, and reflective outcomes. The new validated instruments offer a robust measurement model for academic coaching.

Project description:BackgroundThe optimal biomarkers for early diagnosis, treatment, and prognosis of tuberous sclerosis complex (TSC)-associated epilepsy are not yet clear. This study identifies the crucial genes involved in the pathophysiology of TSC-associated epilepsy via a bioinformatics analysis. These genes may serve as novel therapeutic targets.MethodsGene chip data sets (GSE62019 and GSE16969) comprising the data of patients with TSC-associated epilepsy and healthy control participants were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in the GEO database were identified using the GEO2R gene expression analysis tool. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, Gene Ontology function, and protein-protein interaction (PPI) network analyses were then conducted. The results were analyzed using R language, and are presented in volcano plots, Venn diagrams, heatmaps, and enrichment pathway bubble charts. A gene set enrichment analysis (GSEA), was conducted to examine the KEGG pathways and crucial genes linked to TSC-associated epilepsy. The potential genes were compared with the genes listed in the Online Mendelian Inheritance in Man (OMIM) database and analyzed against the literature to determine their clinical significance. Finally, the expression of the key genes in the TSC-associated epilepsy mice cerebral cortex was examined through immunohistochemical staining.ResultsThe intersection of the GSE62019 and GSE16969 data sets revealed 151 commonly upregulated DEGs. The KEGG enrichment analysis indicated that these DEGs affected the occurrence and development of TSC-associated epilepsy by modulating complement and coagulation cascades, glycosaminoglycans in cancer, and extracellular matrix-receptor interactions. Four high-scoring clusters emerged, and podoplanin (PDPN) was identified as a key gene through the construction of a PPI network of the common DEGs using the Cytoscape software. A GSEA of the DEGs revealed that the common DEG PDPN was enriched in both data sets in pathways related to platelet activation, aggregation, and the glycoprotein VI (GPVI)-mediated activation cascade. Immunohistochemical staining revealed a significant elevation in PDPN expression in the cerebral cortex of mice with TSC-associated epilepsy. Conversely, the control group mice did not display any significantly positive neurons.ConclusionsThe discovery of these crucial genes and signaling pathways extends understanding of the molecular processes underlying the development of TSC-associated epilepsy. Additionally, our findings may provide a theoretical basis for research into targeted clinical treatments.

Dataset Information

Measuring Health-Related Quality of Life in Tuberous Sclerosis Complex - Psychometric Evaluation of Three Instruments in Individuals With Refractory Epilepsy.

Publications

Measuring Health-Related Quality of Life in Tuberous Sclerosis Complex - Psychometric Evaluation of Three Instruments in Individuals With Refractory Epilepsy.

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