Work, daily activities and leisure after cancer.

OBJECTIVE: Determine if cancer survivors have lower participation in paid work, more limitations in daily activities or more limitations in leisure compared with those without cancer, stratified by age (working age ≤65 years; retirement age >65 years). Secondary objectives are identifying sociodemographic or clinical factors associated with work, daily activities or leisure and analysis of the relationship between work, daily activities and leisure. METHODS: Secondary analyses, using logistic regression, were performed on three cohorts (lymphoma, prostate and thyroid cancer) from the Dutch Patient Reported Outcomes Following Initial treatment and Long-term Evaluation of Survivorship (PROFILES) registry and a nationally representative non-cancer sample. RESULTS: Working-age cancer survivors (n = 926) were significantly (p < 0.001) less likely to participate in paid work and more likely to report limitations in daily activities and leisure compared to the non-cancer cohort (n = 1279). Among retirement aged cancer survivors (n = 1046), paid work was significantly more likely (p < 0.001), as were limitations in leisure (p < 0.05), compared with the non-cancer controls (n = 334). CONCLUSIONS: Cancer impacts daily activities and leisure, as well as paid work. These roles are important for cancer survivors' quality of life, suggesting support to return to these activities may be an important component of survivorship care.

Enthalpy-Driven Stabilization of Transthyretin by AG10 Mimics a Naturally Occurring Genetic Variant That Protects from Transthyretin Amyloidosis.

Transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) is a fatal disease with no available disease-modifying therapies. While pathogenic TTR mutations (TTRm) destabilize TTR tetramers, the T119M variant stabilizes TTRm and prevents disease. A comparison of potency for leading TTR stabilizers in clinic and structural features important for effective TTR stabilization is lacking. Here, we found that molecular interactions reflected in better binding enthalpy may be critical for development of TTR stabilizers with improved potency and selectivity. Our studies provide mechanistic insights into the unique binding mode of the TTR stabilizer, AG10, which could be attributed to mimicking the stabilizing T119M variant. Because of the lack of animal models for ATTR-CM, we developed an in vivo system in dogs which proved appropriate for assessing the pharmacokinetics-pharmacodynamics profile of TTR stabilizers. In addition to stabilizing TTR, we hypothesize that optimizing the binding enthalpy could have implications for designing therapeutic agents for other amyloid diseases.