RESUMO
PURPOSE: Patient Reported Outcomes Quality of Life survey for HCV (PROQOL-HCV) is a specific tool developed to assess health-related quality of life (HRQoL) in patients with chronic hepatitis C receiving direct-acting antivirals (DAA). Thresholds for clinically meaningful changes in PROQOL-HCV scores should be documented to improve the tool's use in clinical practice. This study aimed to estimate the minimal clinically important differences (MCIDs) in PROQOL-HCV scores before and after HCV cure by DAA among participants in the prospective cohort ANRS-CO22 HEPATHER. METHODS: Data from 460 chronic HCV patients were collected at DAA initiation (baseline) and 24 weeks after treatment end. MCIDs were estimated for the six HRQoL dimensions (Physical Health (PH), Emotional Health (EH), Future Uncertainty (FU), Intimate Relationships (IR), Social Health (SH), and Cognitive Functioning (CF)) using two approaches: anchor-based and score distribution-based. Each MCID was estimated for improvement/deterioration both globally and separately for patients with a baseline PRQoL-HCV score ≤ 50 (group1) and patients with a baseline PRQoL-HCV score > 50 (group2). RESULTS: The pooled MCIDs for improvement/deterioration globally, in group1, and in group2, respectively, were as follows: 8.8/- 7.6, 9.7/- 9.5, and 6.0/- 6.9 for PH; 7.1/- 4.6, 7.7/- 9.6, and 6.6/- 6.7 for EH; 6.7/- 6.7, 8.2/- 8.2, and 6.0/- 6.0 for FU; 7.0/- 7.0, 5.4/- 5.4, and 6.2/- 6.2 for IR; 7.7/- 7.7, 8.6/- 8.6, and 6.5/- 6.5 for SH; 7.3/- 5.6, 9.1/- 8.0, and 6.5/- 6.3 for CF. CONCLUSIONS: The overall MCID for the PROQOL-HCV scores ranged from 6.7 to 8.8 for improvement and from - 7.7 to - 4.6 for deterioration. The effect of DAA on PROQOL-HCV scores seemed particularly beneficial for patients with lower baseline scores. This subgroup could be motivated to take DAA if they are informed of the benefits for their HRQoL.
RESUMO
Insulin and amino acids are key factors in regulating protein synthesis. The mechanisms of their action have been widely studied for several years. The insulin signal is mediated by the activation of intracellular kinases such as phosphatidylinositol-3'kinase and the mammalian target of rapamycin (mTOR), affecting the phosphorylation of some major effectors involved in the regulation of translation initiation, i.e. p70 S6 kinase (p70S6K) and the translational repressor eukaryotic initiation factor 4E binding protein (4E-BP1). The amino acid-induced signalling cascade also originates from mTOR and promotes p70S6K and 4E-BP1 activation. However, the mechanisms of regulation are complex and little understood, especially in vivo. Elucidating these mechanisms is important for both fundamental physiology and nutritional applications, i.e. better control of the use of nutrients and optimisation of dietary amino acid supplies in various physiological and physiopathological situations. In comparative physiology, the chicken is an interesting model to gain better understanding of the nutritional regulation of mRNA translation because of the very high rates of muscle growth and protein synthesis, and the unusual features compared with mammals. In the present review we provide an overview of the roles of insulin and amino acids as regulators of protein synthesis in both mammals and avian species.
