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- Tran, DL, et al.
(author)
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Exercise Intolerance, Benefits, and Prescription for People Living With a Fontan Circulation: The Fontan Fitness Intervention Trial (F-FIT)-Rationale and Design
- 2022
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In: Frontiers in pediatrics. - : Frontiers Media SA. - 2296-2360. ; 9, s. 799125-
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Journal article (peer-reviewed)abstract
- Background: Despite developments in surgical techniques and medical care, people with a Fontan circulation still experience long-term complications; non-invasive therapies to optimize the circulation have not been established. Exercise intolerance affects the majority of the population and is associated with worse prognosis. Historically, people living with a Fontan circulation were advised to avoid physical activity, but a small number of heterogenous, predominantly uncontrolled studies have shown that exercise training is safe—and for unique reasons, may even be of heightened importance in the setting of Fontan physiology. The mechanisms underlying improvements in aerobic exercise capacity and the effects of exercise training on circulatory and end-organ function remain incompletely understood. Furthermore, the optimal methods of exercise prescription are poorly characterized. This highlights the need for large, well-designed, multi-center, randomized, controlled trials.Aims and Methods: The Fontan Fitness Intervention Trial (F-FIT)—a phase III clinical trial—aims to optimize exercise prescription and delivery in people with a Fontan circulation. In this multi-center, randomized, controlled study, eligible Fontan participants will be randomized to either a 4-month supervised aerobic and resistance exercise training program of moderate-to-vigorous intensity followed by an 8-month maintenance phase; or usual care (control group). Adolescent and adult (≥16 years) Fontan participants will be randomized to either traditional face-to-face exercise training, telehealth exercise training, or usual care in a three-arm trial with an allocation of 2:2:1 (traditional:telehealth:control). Children (<16 years) will be randomized to either a physical activity and exercise program of moderate-to-vigorous intensity or usual care in a two-arm trial with a 1:1 allocation. The primary outcome is a change in aerobic exercise capacity (peak oxygen uptake) at 4-months. Secondary outcomes include safety, and changes in cardiopulmonary exercise testing measures, peripheral venous pressure, respiratory muscle and lung function, body composition, liver stiffness, neuropsychological and neurocognitive function, physical activity levels, dietary and nutritional status, vascular function, neurohormonal activation, metabolites, cardiac function, quality of life, musculoskeletal fitness, and health care utilization. Outcome measures will be assessed at baseline, 4-months, and 12-months. This manuscript will describe the pathophysiology of exercise intolerance in the Fontan circulation and the rationale and protocol for the F-FIT.
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| 2. |
- Praveen, Kavita, et al.
(author)
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Population-scale analysis of common and rare genetic variation associated with hearing loss in adults
- 2022
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In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 540-540
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Journal article (peer-reviewed)abstract
- To better understand the genetics of hearing loss, we performed a genome-wide association meta-analysis with 125,749 cases and 469,497 controls across five cohorts. We identified 53/c loci affecting hearing loss risk, including common coding variants in COL9A3 and TMPRSS3. Through exome sequencing of 108,415 cases and 329,581 controls, we observed rare coding associations with 11 Mendelian hearing loss genes, including additive effects in known hearing loss genes GJB2 (Gly12fs; odds ratio [OR] = 1.21, P = 4.2 × 10-11) and SLC26A5 (gene burden; OR = 1.96, P = 2.8 × 10-17). We also identified hearing loss associations with rare coding variants in FSCN2 (OR = 1.14, P = 1.9 × 10-15) and KLHDC7B (OR = 2.14, P = 5.2 × 10-30). Our results suggest a shared etiology between Mendelian and common hearing loss in adults. This work illustrates the potential of large-scale exome sequencing to elucidate the genetic architecture of common disorders where both common and rare variation contribute to risk.
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