Proposed Denosumab Biosimilar SB16 vs Reference Denosumab in postmenopausal osteoporosis: phase 3 results up to month 12

Context SB16 is a proposed biosimilar to reference denosumab (DEN; brand name: Prolia). Objective This phase 3 randomized, double-blind, multicenter study evaluated the biosimilarity of SB16 to DEN in women with postmenopausal osteoporosis (NCT04664959). Design The study included 457 postmenopausal osteoporosis patients who had a lumbar spine or total hip T-score between −2.5 and −4. Patients were randomized in a 1:1 ratio to receive either 60 mg of SB16 or DEN subcutaneously at month 0 and month 6. At month 12, patients were rerandomized to continue with the assigned treatment or switch from DEN to SB16 up to month 18. This report includes results up to month 12. Methods The primary endpoint was the percent change from baseline in lumbar spine bone mineral density (BMD) at month 12. Secondary endpoints including the percent change from baseline in BMD of the lumbar spine (except for month 12), total hip, and femoral neck; pharmacokinetic, pharmacodynamic (serum C-telopeptide of type I collagen, and procollagen type I N-terminal propeptide), safety, and immunogenicity profiles were measured up to month 12. Results The least-squares mean differences in percent change from baseline in lumbar spine BMD at month 12 were 0.33% (90% CI, −0.25 to 0.91) in the full analysis set and 0.39% (95% CI, −0.36 to 1.13) in the per-protocol set; both within the predefined equivalence margin. The secondary endpoints were comparable between the 2 treatment groups. Conclusion The reported efficacy, pharmacokinetic, pharmacodynamic, safety, and immunogenicity data support the biosimilarity of SB16 to DEN

Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Solvation effect of bacteriochlorophyll excitons in light-harvesting complex LH2

AbstractWe have characterized the influence of the protein environment on the spectral properties of the bacteriochlorophyll (Bchl) molecules of the peripheral light-harvesting (or LH2) complex from Rhodobacter sphaeroides. The spectral density functions of the pigments responsible for the 800 and 850nm electronic transitions were determined from the temperature dependence of the Bchl absorption spectra in different environments (detergent micelles and native membranes). The spectral density function is virtually independent of the hydrophobic support that the protein experiences. The reorganization energy for the B850 Bchls is 220cm−1, which is almost twice that of the B800 Bchls, and its Huang-Rhys factor reaches 8.4. Around the transition point temperature, and at higher temperatures, both the static spectral inhomogeneity and the resonance interactions become temperature-dependent. The inhomogeneous distribution function of the transitions exhibits less temperature dependence when LH2 is embedded in membranes, suggesting that the lipid phase protects the protein. However, the temperature dependence of the fluorescence spectra of LH2 cannot be fitted using the same parameters determined from the analysis of the absorption spectra. Correct fitting requires the lowest exciton states to be additionally shifted to the red, suggesting the reorganization of the exciton spectrum

Estimating cancer risk from dental cone-beam CT exposures based on skin dosimetry

The aim of this study was to measure entrance skin doses on patients undergoing cone-beam computed tomography (CBCT) examinations, to establish conversion factors between skin and organ doses, and to estimate cancer risk from CBCT exposures. 266 patients (age 8-83) were included, involving three imaging centres. CBCT scans were acquired using the SCANORA 3D (Soredex, Tuusula, Finland) and NewTom 9000 (QR, Verona, Italy). Eight thermoluminescent dosimeters were attached to the patient's skin at standardized locations. Using previously published organ dose estimations on various CBCTs with an anthropomorphic phantom, correlation factors to convert skin dose to organ doses were calculated and applied to estimate patient organ doses. The BEIR VII age- and gender-dependent dose-risk model was applied to estimate the lifetime attributable cancer risk. For the SCANORA 3D, average skin doses over the eight locations varied between 484 and 1788μGy. For the NewTom 9000 the range was between 821 and 1686μGy for Centre 1 and between 292 and 2325μGy for Centre 2. Entrance skin dose measurements demonstrated the combined effect of exposure and patient factors on the dose. The lifetime attributable cancer risk, expressed as the probability to develop a radiation-induced cancer, varied between 2.7 per million (age >60) and 9.8per million (age 8-11) with an average of 6.0 per million. On average, the risk for female patients was 40% higher. The estimated radiation risk was primarily influenced by the age at exposure and the gender, pointing out the continuing need for justification and optimization of CBCT exposures, with a specific focus on children. © 2014 Institute of Physics and Engineering in Medicine