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BackgroundTreatment of Hepatitis C virus (HCV) infection has evolved from interferon (IFN)-based treatments to direct-acting antivirals (DAAs). Patients with HCV have an elevated psychiatric morbidity (including substance abuse) and patients with such comorbidity have often been excluded from treatment with IFN. To date, little is known about psychiatric adverse effects of DAA-based regimens. We therefore aimed to study the psychiatric side effects of new IFN-free treatment for HCV (including depressive symptoms and sleep) in real world patients also including those with a history of psychiatric diagnosis, substance abuse or drug dependence.MethodsConsecutive patients were monitored during treatment with three of the latest DAA agents (sofosbuvir, simeprevir and daclatasvir). Repeated expert psychiatric assessments from baseline to 12 weeks post-treatment were performed with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) clinical version and the self-report versions of the Montgomery Åsberg Depression Rating Scale (MADRS-S) and the Pittsburgh Sleep Quality Index (PSQI). Friedman’s test was performed to calculate differences in the MADRS-S and PSQI over time. In a post-hoc analysis Wilcoxon’s test was used to compare baseline depressive symptoms with those at post-treatment. Spearman’s rank correlation test was conducted in another post-hoc analysis to evaluate the correlation between symptoms of depression and HCV viral load at baseline.ResultsAt baseline, 15/17 patients (88%) had a history of any psychiatric diagnosis; 11 (65%) had a history of substance abuse or dependence; and 11 (65%) had previously been treated with IFN and six of those had experienced psychiatric side effects. There was no correlation between depressive symptoms and HCV viral load at baseline. Symptoms of depression did not increase during DAA treatment and were lower 12 weeks post-treatment compared with baseline: MADRS-S 10.7 vs. 8.3 (p = 0.01). This observation held when excluding patients taking antidepressant medication. Sleep quality did not significantly change during treatment. Adherence to treatment was estimated to 95% and sustained virological response was 88%.ConclusionsDespite high psychiatric morbidity, including previous substance abuse, patients successfully completed DAA treatment without increasing depressive symptoms or sleep disturbance. Symptoms of depression were significantly reduced 12 weeks after DAA treatment.

Serum amyloid A (SAA) protein is an acute phase reactant that has recently become of increasing interest as a marker for disease and treatment monitoring. We have correlated SAA levels to those of C-reactive protein (CRP) in sera from 98 patients admitted to an infectious diseases clinic because of viral and bacterial infections, including hepatitis A and B, cytomegalovirus infection, varicellae-zoster, infectious mononucleosis, influenza A, bacterial pneumonia, streptococcal pharyngitis, bacterial sepsis and severe bacterial sepsis. The study population was chosen from the clinical setting as representatives of these frequently encountered patient groups. SAA levels correlated significantly with CRP levels (r2=0.757, p<0.001) for the entire studied population. Furthermore, positive correlations were found in viral (r2=0.572, p<0.001) and bacterial (r2=0.666, p<0.001) infections. Positive correlations were also observed when the values were compared in accordance with CRP levels higher and lower than 100 mg/L (r2=0.689, p<0.001; CRP>100; r2=0.397, p<0.001; CRP<100). Because SAA is more sensitive than CRP for the detection of minor inflammatory stimuli, as in the viral and low CRP groups, we conclude that SAA can be of use in several viral infections, as well as in non-invasive and early invasive bacterial infections.

Using this method, baseline resistance can be examined and the data could have a potential role in selecting the optimal and cost-efficient treatment for the patient.

AimsSince cefuroxime mainly is excreted by renal filtration, dosing is currently based on serum creatinine (Scr) or creatinine clearance (CLcr). However, it has been suggested that cystatin C (CysC) is superior to Scr as a marker of renal function. The aim of this prospective study was to develop a population model that describes the pharmacokinetics of cefuroxime and to investigate the usefulness of CysC as a covariate of the model parameters. MethodsNinety-seven patients were studied (CLcr range 6.5-115 ml min − 1 ). Blood samples ( n = 407) for the determination of cefuroxime were withdrawn according to a sparse data sampling schedule and analysed by liquid chromatography mass spectrometry. The population analysis was performed in NONMEM. ResultsA two-compartment model described the data well. The biomarkers Scr, CLcr and CysC were evaluated as covariates on clearance (CL). The model that included CysC generated the best fit. In the final population model CL was a function of CysC and body weight, whereas V 1 was only a function of body weight. Final parameter estimates (relative standard errors) were 6.00 (3.2%) l h − 1 , 11.4 (5.3%) l and 5.11 (11%) l for CL, V 1 and V 2 , respectively. ConclusionsBased on the results of the present study, and because CysC is practical to use in the clinic, it is suggested that individual dosing of cefuroxime may be based on CysC rather than on Scr or CLcr. Furthermore, our final population model may be useful as a tool when designing new dosing schedules for cefuroxime.