The impact of ribavirin exposure on sustained virological response (SVR) in patients with chronic hepatitis C is unknown. Preliminary studies showed marked inter-individual variability of ribavirin concentrations despite dose adjustment for body weight (BW) and suggested there was a correlation between single time point concentrations and SVR. None of them evaluated the global exposure to ribavirin. This study was conducted to determine whether early ribavirin global exposure is related with SVR. An exploratory pharmacokinetic-pharmacodynamic (PK-PD) study was conducted in genotype 1 hepatitis C patients treated with peginterferon alfa-2a and ribavirin (dose-adjusted for BW) for 12 weeks, to which amantadine was added for the following 36 weeks. 03). Patients with D0AUCs above the cut-off values defined by receiver operating characteristic curves (3014 g/hour/L and 1755 g/hour/L for AUC 0-12h and AUC 0-4h , respectively) had a significantly better chance of achieving an SVR than patients with AUCs under the thresholds (odds ratio ‫؍‬ 16.0, 95% confidence interval 1.54-166.6, P ‫؍‬ 0.02 and odds ratio ‫؍‬ 8.9, 95% confidence interval, 1.4-56.6; P ‫؍‬ 0.02). Conclusion: Ribavirin exposure at D0 is significantly related to SVR. To our knowledge, this is the first study to give an early pharmacokinetic predictor of SVR. We propose a minimum AUC 0-4h threshold of 1755 g/hour/L at D0 as a target for ribavirin dose adjustment.

ObjectivesGiant cell arteritis (GCA) is a chronic systemic vasculitis of large and medium-sized arteries, for which long-term glucocorticoid (GC) treatment is needed. During GC withdrawal patients can suffer adrenal insufficiency. We sought to determine the time until recovery of adrenal function after long-term GC therapy, and to assess the prevalence and predictors for secondary adrenal insufficiency.Subjects and Design150 patients meeting the ACR criteria for GCA between 1984 and 2012 were analyzed. All received the same GC treatment protocol. The low-dose ACTH stimulation test was repeated annually until adrenal recovery. Biographical, clinical and laboratory data were collected prospectively and compared.ResultsAt the first ACTH test, 74 (49%) patients were non-responders: of these, the mean time until recovery of adrenal function was 14 months (max: 51 months). A normal test response occurred within 36 months in 85% of patients. However, adrenal function never recovered in 5% of patients. GC of >15 mg/day at 6 months, GC of >9.5 mg/day at 12 months, treatment duration of >19 months, a cumulative GC dose of >8.5 g, and a basal cortisol concentration of <386 nmol/L were all statistically associated with a negative response in the first ACTH test (p <0.05).ConclusionAdrenal insufficiency in patients with GCA, treated long-term with GC, was frequent but transitory. Thus, physicians’ vigilance should be increased and an ACTH test should be performed when GC causes the above associated statistical factors.

Although AMs are frequent and usually mild in pSS, these manifestations are associated with a pluri-systemic involvement of pSS.

Although pSS is typically a disease affecting women, clinicians should be aware that it may be diagnosed in male patients. Except for haematological presentation, we could not find any notable differences in clinical and immunological characteristics between male and female patients with pSS.

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