Relevance to investigate different stages of pregnancy to highlight toxic effects of nanoparticles: The example of silica.

Amorphous silica nanoparticles (SiO2NPs) have been recognized as safe nanomaterial, hence their use in biomedical applications has been explored. Data, however, suggest potential toxicity of SiO2 NPs in pregnant individuals. However, no studies relating nanoparticle biokinetic/toxicity to the different gestational stages are currently available. In this respect, we have investigated the possible embryotoxic effects of three-size and two-surface functionalization SiO2NPs in mice. After intravenous administration of different concentrations at different stages of pregnancy, clinical and histopathological evaluations, performed close to parturition, did not show signs of maternal toxicity, nor effects on placental/fetal development, except for amino-functionalized 25 nm NPs. Biodistribution was studied by ICP-AES 24 h after administration, and demonstrates that all particles distributed to placenta and conceptuses/fetuses, although size, surface charge and gestational stage influenced biodistribution. Our data suggest the need of comprehensive toxicological studies, covering the entire gestation to reliably assess the safety of nanoparticle exposure during pregnancy.

Cost-effectiveness and budget impact analysis of viscosupplementation with hylan G-F 20 for knee and hip osteoarthritis.

PURPOSE: To estimate the cost-effectiveness and budget impact of viscosupplementation with one intra-articular (IA) injection of 6 mL hylan G-F 20 (Synvisc-One®) and with three injections of 2 mL hylan G-F 20 (Synvisc®3×2) in knee osteoarthritis (OA) patients compared with conventional support therapy (CST - eg, NSAIDs and acetaminophen) and the cost-effectiveness of one IA injection of 2 mL hylan G-F 20 (Synvisc®1×2) in hip OA patients compared with CST from an Italian Health System perspective. METHODS: The model used was a Markov model with states for stages II-IV on the Kellgren-Lawrence scale and runs on 6-month cycles over a 5-year time horizon. A 3.5% discount was applied to both costs and utilities. Direct costs were determined from the perspective of the Italian National Health Service. A one-way and probabilistic sensitivity analysis was conducted for both comparisons. RESULTS: Hylan G-F 20 1×6 mL and hylan G-F 20 3×2 mL for knee OA were very likely to be cost-effective when compared to acetaminophen (ICER = €3,160.61 and €3,845.81 per QALY, respectively) and NSAIDs as both ICERs are below €25,000. The hip OA treatment by hylan G-F 20 1×2 mL was dominant compared to NSAIDs and very likely compared to acetaminophen. The results of the cost-effectiveness analysis were confirmed by one-way sensitivity analysis. The budget impact analysis for knee and hip OA showed a small increase in expenditure during 5 years. CONCLUSIONS: Hylan G-F 20 1×6 mL/hylan G-F 20 is a cost-effectiveness treatment compared to NSAIDs and acetaminophen in the treatment of knee/hip OA in Italy. The treatment of hip and knee OA resulted in cost-saving with hylan G-F 20 1×2 mL and economically sustainable with hylan G-F 20 1×6 mL. However, Real Word Evidence studies should be conducted in order to estimate costs associated with both prosthetics and to understand the reduction of physiotherapy and medication due to hylan G-F 20.