Medical Therapies for Uterine Fibroids - A Systematic Review and Network Meta-Analysis of Randomised Controlled Trials

BACKGROUND: Uterine fibroids are common, often symptomatic and a third of women need repeated time off work. Consequently 25% to 50% of women with fibroids receive surgical treatment, namely myomectomy or hysterectomy. Hysterectomy is the definitive treatment as fibroids are hormone dependent and frequently recurrent. Medical treatment aims to control symptoms in order to replace or delay surgery. This may improve the outcome of surgery and prevent recurrence. PURPOSE: To determine whether any medical treatment can be recommended in the treatment of women with fibroids about to undergo surgery and in those for whom surgery is not planned based on currently available evidence. STUDY SELECTION: Two authors independently identified randomised controlled trials (RCT) of all pharmacological treatments aimed at the treatment of fibroids from a list of references obtained by formal search of MEDLINE, EMBASE, Cochrane library, Science Citation Index, and ClinicalTrials.gov until December 2013. DATA EXTRACTION: Two authors independently extracted data from identified studies. DATA SYNTHESIS: A Bayesian network meta-analysis was performed following the National Institute for Health and Care Excellence-Decision Support Unit guidelines. Odds ratios, rate ratios, or mean differences with 95% credible intervals (CrI) were calculated. RESULTS AND LIMITATIONS: A total of 75 RCT met the inclusion criteria, 47 of which were included in the network meta-analysis. The overall quality of evidence was very low. The network meta-analysis showed differing results for different outcomes. CONCLUSIONS: There is currently insufficient evidence to recommend any medical treatment in the management of fibroids. Certain treatments have future promise however further, well designed RCTs are needed

Transport and retention of aqueous dispersions of superparamagnetic nanoparticles in sandstone

We evaluate the transport of surface-treated superparamagnetic iron-oxide nanoparticles in Boise-sandstone rocks by injecting aqueous dispersions of the particles into core plugs. Several different surface treatments yield stable dispersions of these particles, but provide very different transport characteristics. Effluent concentration histories are measured to obtain the particle retention in the rock. The results are used to optimize the particle surface coating so that the reservoir application requirements for the functional nanoparticles can be achieved. The application of interest here requires the nanoparticles to adsorb to oil/water interfaces. Our earlier experiments (Yu et al., 2010) showed that the paramagnetic nanoparticles stabilized with small negatively-charged citrate ligands have little retention in sedimentary rocks, but their preferred adsorption at the oil/water interfaces in rock pores was not achieved. A major improvement in surface coating optimization is achieved by creating a crosslinked polymer film that wraps around the nanoparticle so that it does not detach from the particle surface even under the harsh reservoir conditions. To fine-tune the coating to satisfy the reservoir application requirements, co-polymers and ter-polymers with different constituent monomers are employed. Nanoparticles stabilized with (polystyrene sulfonate-alt-maleic acid) coating show a good adsorption tendency at the oil/water interfaces, while with very low adsorption at rock surface (similar to 0.02 mg/m(2)). The dispersion also has long-term stability even at high salinity (8 wt% NaCl). Other polymers, such as (polyacrylic acid-r-butyl acrylate), (polyacrylic acid-b-styrene sulfonic acid), and (polyacrylic acid-r-butyl acrylate-b-styrene sulfonic acid), were also tested. The coating with the last polymer (PAA-PBA-PSS) provides a very low retention of particles in the rock, but only marginal preferred adsorption at oil/water interfaces. (C) 2014 Elsevier B.V. All rights reserved

Covalently linked au nanoparticles to a viral vector: Potential for combined photothermal and gene cancer therapy

Hyperthermia can be produced by near-infrared laser irradiation of gold nanoparticles present in tumors and thus induce tumor cell killing via a bystander effect. To be clinically relevant, however, several problems still need to be resolved, In particular, selective delivery and physical targeting of gold nanoparticles to tumor cells are necessary to improve therapeutic selectivity. Considerable progress has been made with respect to retargeting adenoviral vectors for cancer gene therapy. We therefore hypothesized that covalent coupling of gold nanoparticles to retargeted adenoviral vectors would allow selective delivery of the nanoparticles to tumor cells, thus feasibilizing hyperthermia and gene therapy as a combinatorial therapeutic approach. For this, sulfo-N-hydroxysuccinimide labeled gold nanoparticles were reacted to adenoviral vectors encoding a luciferase reporter gene driven by the cytomegalovirus promoter (AdCMVLuc). We herein demonstrate that covalent coupling could be achieved, while retaining virus infectivity and ability to retarget tumor-associated antigens. These results indicate the possibility of using adenoviral vectors as carriers for gold nanoparticles

Iron Oxide Nanoparticles Grafted with Sulfonated and Zwitterionic Polymers: High Stability and Low Adsorption in Extreme Aqueous Environments

A facile grafting through approach was developed to tether tunable quantities of poly(2-acrylamido-2-methylpropanesulfonic acid) (PAMPS) as well as zwitterionic poly([3-(methacryloylamino)propyl]dimethyl(3-sulfopropyl)ammonium hydroxide) (PMPDSA) homopolymer onto iron oxide (IO) nanoparticles (NPs). In this case, homopolymers may be grafted, unlike grafting to approaches that often require copolymers containing anchor groups. The polymer coating provided steric stabilization of the NP dispersions at high salinities and elevated temperature (90 degrees C) and almost completely prevented adsorption of the NPs on silica microparticles and crushed Berea sandstone. The adsorption of PAMPS IO NPs decreased with the polymer loading, whereby the magnitude of the particle-surface electrosteric repulsion increased. The zwitterionic PMPDSA IO NPs displayed 1 order of magnitude less adsorption onto crushed Berea sandstone relative to the anionic PAMPS IO NPs. The ability to design homopolymer coatings on nanoparticle surfaces by the grafting through technique is of broad interest for designing stable dispersions and modulating the interactions between nanoparticles and solid surfaces

Clinical Activity of Pazopanib in Metastatic Extraosseous Ewing Sarcoma

We report a response to pazopanib in a 69-year-old man with heavily pre-treated metastatic extraosseous Ewing sarcoma in addition to molecular profiling of his tumor. To our knowledge, this case is the earliest to demonstrate activity of an oral multi-targeted kinase inhibitor in Ewing sarcoma. This case provides rationale for adding a Ewing sarcoma arm to SARC024, a phase II study of regorafenib, another multi-targeted kinase inhibitor, in patients with liposarcoma, osteosarcoma and Ewing and Ewing-like sarcomas (NCT02048371). This national multi-institutional study is ongoing