Psychological complications in patients with acromegaly: relationships with sex, arthropathy, and quality of life.

PURPOSE: Current treatment of acromegaly restores a normal life expectancy in most cases. So, the study of persistent complications affecting patients' quality of life (QoL) is of paramount importance, especially motor disability and depression. In a large cohort of acromegalic patients we aimed at establishing the prevalence of depression, to look for clinical and sociodemographic factors associated with it, and to investigate the respective roles (and interactions) of depression and arthropathy in influencing QoL. METHODS: One hundred and seventy-one acromegalic patients (95 women and 76 men, aged 20-85 years) among those recruited in a cross-sectional Italian multicentric study were investigated. Each patient filled in three validated questionnaires: AcroQoL, WOMAC (measuring articular pain, stiffness and functionality), and AIMS (evaluating articular symptoms and depression). RESULTS: A very high (up to 28%) depression rate was detected in acromegalic subjects. Two patients showing pathological AIMS depression scores, committed suicide during the three years observational period. In our population poor psychological status was significantly associated with female sex. Furthermore, a significant strong correlation was found between AIMS depression score and WOMAC score. Both depression and arthropathy-related motor disability turned out to independently contribute with similar strength to the impairment of QoL. CONCLUSIONS: We report a high prevalence of depression in acromegaly, which is associated with female sex and arthropathy. Both depression and arthropathy strongly and independently contribute to the impaired QoL of patients. Our study shows that assessment and monitoring of psychological status is mandatory in acromegaly, also suggesting an inexpensive tool for this assessment.

Directly acting antivirals against hepatitis C virus: mechanisms of action and impact of resistant associated variants.

Hepatitis C virus (HCV) drug development has resulted in interferon-free (IFN) regimens of direct-acting antivirals (DAAs). The new therapies are highly effective achieving 90-95% of sustained virologic response (SVR) rates among all genotypes with minimal treatment-related side effects. They opened a new scenario in HCV treatment representing a treatment option for patients who were ineligible to IFN-based regimens as those with decompensated liver disease, autoimmune disorders and psychiatric disturbs. However, numerous research and clinical questions remain. In particular, drug resistance is an upcoming clinical issue in HCV treatment. The aim of this review is to provide an overview of the different DAAs approved or in clinical development and their mechanism of actions. For each class of agents the resistance profile will be examined according to the available in vitro and in vivo data discussing the clinical implications. Resistance-associated variants (RAVs) are driven by the selection of mutations at different virologic targets. The most clinically relevant NS3/4A protease substitutions are detected at positions V36, Q80, T54, R155 and A156. S282T is the most frequent NS5B polymerase aminoacids substitutions. M28, Q30, L31 and Y39 mutations are involved in NS5A proteins associated resistance. The baseline RAVs seems not to affect the SVR rates. Thus, their detection by sequencing analysis should not to be recommended. Conversely, RAVs testing after DAAs failure is of clinical practice concern in order to select the most appropriate retreatment combination.