Pharmacokinetics and pharmacodynamics of multiple doses of BG00010, a neurotrophic factor with anti-hyperalgesic effects, in patients with sciatica

AIMS: BG00010 is a protein in the glial cell line-derived neurotrophic factor (GDNF) family. It is a selective ligand for the GDNF family receptor alpha-3 (GFRα3) co-receptor that normalizes cellular changes resulting from damage or disease, and potentially alleviates neuropathic pain. The main objectives of this study were to evaluate the pharmacokinetic and safety profiles and to determine the effects on pain of ascending doses of intravenous injections of BG00010 in patients with sciatica.METHODS: This was a randomized, blinded, placebo-controlled multiple-dose study in subjects with sciatica. In Part I (16 patients), four IV dose levels were examined (50, 150, 400, 800 μg kg(-1) ) and in Part II (12 patients), three dose levels were examined (400, 600 and 1200 μg kg(-1) ). Safety and efficacy assessments were used as endpoints.RESULTS: The BG00010 concentration-time data indicated relatively low inter-patient variability and there was a dose-dependent (not dose-proportional) increase in serum exposure from 150 to 1200 μg kg(-1) . The effective half-life was between 40 and 60 h. The most frequently occurring adverse events (AEs) reported by patients receiving BG00010 were headache (67-83%), feeling hot (50-100%), and pruritus (42-67%). Most AEs were mild; no serious AEs or AEs leading to discontinuation occurred. Higher dose regimens of BG00010 resulted in greater pain reduction than placebo or lower dose regimens, although a clear dose-response relationship was not seen.CONCLUSIONS: The pharmacokinetic profile of BG00010 was characterized by low intra-patient variability. These data from a small sample suggest that BG00010 may have a benefit for patients with sciatica.TRIAL REGISTRATION: ClinicalTrials.gov NCT00961766 NCT01405833.Perioperative Medicine: Efficacy, Safety and Outcom

Reducing social anxiety in adolescents distressed by a visible difference: Results from a randomised control trial of a web-based intervention

A visible difference to the face or body may challenge adolescents’ adjustment and engagement in life activities, where some require psychosocial support. However, evidence is limited for whether existing interventions for this adolescent group reduce social or appearance-related distress. We therefore conducted a parallel-group, randomised control trial to evaluate the effectiveness of Young Person's Face IT, a self-guided web-based psychosocial intervention developed for adolescents with a visible difference who experience distress. Adolescents (N = 189, aged 11–18) from two countries (Norway and the Netherlands), were randomly allocated to an intervention group or care as usual (CAU). Outcomes were body esteem, social anxiety, perceived stigmatisation, and life disengagement. Compared with CAU, participants who completed Young Person's Face IT showed reductions in social anxiety symptoms (ηp2 = 0.06). No significant improvements were found for the other outcomes. This study endorses web-based psychosocial support in reducing social anxiety in adolescents distressed by a visible difference. Future studies are needed to confirm the effectiveness of Young Person's Face IT and to explore potential long-term effects

The Impact of Immigration on the Wage Distribution in Switzerland

Recent immigrants in Switzerland are overrepresented at the top of the wage distribution in high and at the bottom in low skill occupations. Basic economic theory thus suggests that immigration has led to a compression of the wage distribution in the former group and to an expansion in the latter. The data confirm this proposition for high skill occupations, but reveal effects close to zero for low skill occupations. While the estimated wage effects are of considerable magnitude at the tails of the wage distribution in high skill occupations, the effects on overall inequality are shown to be negligible