RESUMO
OBJECTIVE: Adolescents and young adult cancer survivors (AYA) are a unique subpopulation with high levels of distress and unmet need. To date, studies have not disentangled distress due to developmental life stage from distress due to cancer survivorship. This population-based study allowed a direct comparison between AYA cancer survivors, older adult (OA) cancer survivors, and their cancer-free peers. METHODS: We combined 4 annual cycles of the Canadian Community Health Survey (CCHS, 2007-2010) to obtain a final sample of 239 316 respondents. We dichotomized the total sample into AYA (15-39 years, n = 83 770) and OA (40+, n = 155 546). Two standardized questions identified cancer survivors (n = 14 592). The self-reported outcomes of interest included self-perceived health and mental health, and health care professional diagnosed mood and anxiety disorders. We used weighted logistic regression models to examine for associations, including an interaction term to assess for effect modification by age. RESULTS: After adjusting for confounders, cancer survivorship in AYAs was strongly associated with higher prevalence of both mood (OR 2.00, 95% CI 1.44-2.77) and anxiety (OR 2.20, 95% CI 1.70-2.86) disorders as compared to their cancer-free peers. OA survivors had a weaker association in the same direction (OR 1.10, 95% CI 1.01-1.21 and OR 1.15, 95% CI 1.02-1.30, respectively). AYA cancer survivors reported higher levels of poor self-perceived mental health than their cancer-free peers (OR 1.49, 95% CI 1.03-2.14), while there was no significant difference from cancer-free peers for OAs (OR 1.03, 95% CI 0.92-1.15). CONCLUSIONS: AYA cancer survivors experience a significantly higher risk of psychosocial distress than both their cancer-free peers and OA survivors.
Assuntos
Ansiedade/psicologia , Sobreviventes de Câncer/psicologia , Neoplasias/psicologia , Grupo Associado , Qualidade de Vida , Estresse Psicológico/psicologia , Adolescente , Fatores Etários , Idoso , Canadá , Feminino , Humanos , Masculino , Saúde Mental , Neoplasias/mortalidade , Neoplasias/patologia , Prevalência , Inquéritos e Questionários , Resultado do Tratamento , Adulto JovemRESUMO
Efforts to optimize biological activity, novelty, selectivity and oral bioavailability of Mps1 inhibitors, from a purine based lead MPI-0479605, are described in this Letter. Mps1 biochemical activity and cytotoxicity in HCT-116 cell line were improved. On-target activity confirmation via mechanism based G2/M escape assay was demonstrated. Physico-chemical and ADME properties were optimized to improve oral bioavailability in mouse.