Obinutuzumab with Bendamustine for Treating Follicular Lymphoma Refractory to Rituximab: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

As part of its single technology appraisal process, the UK National Institute for Health and Care Excellence (NICE) invited the manufacturer of obinutuzumab (Roche) to submit evidence on its clinical and cost effectiveness when used in combination with bendamustine in patients with follicular lymphoma (FL) refractory to rituximab. The Evidence Review Group (ERG), the School of Health and Related Research Technology Appraisal Group at the University of Sheffield, produced a document summarising the key points from the company submission alongside a critical review. Efficacy for progression-free survival (PFS) and safety was positively demonstrated in the pivotal GADOLIN trial, which compared obinutuzumab in combination with bendamustine followed by obinutuzumab maintenance (O-Benda+O) against bendamustine monotherapy. Data on overall survival were immature. The company submitted a model-based economic analysis, including a patient access scheme. The ERG identified a number of limitations, in particular the absence of subgroup analysis and the approach used by the company to estimate overall survival (OS), which was more favourable to the intervention arm. The key uncertainty was the duration of the treatment effect on OS. This uncertainty is expected to be reduced when the final analysis of the GADOLIN trial is reported. Consequently, the NICE appraisal committee recommended O-Benda+O in the population covered by the marketing authorisation within the Cancer Drug Fund until NICE is able to review the guidance following publication of the final analysis of GADOLIN

Co-operative inhibitory effects of hydrogen peroxide and iodine against bacterial and yeast species.

BACKGROUND: Hydrogen peroxide and iodine are powerful antimicrobials widely used as antiseptics and disinfectants. Their antimicrobial properties are known to be enhanced by combining them with other compounds. We studied co-operative inhibitory activities (synergism, additive effects and modes of growth inhibition) of hydrogen peroxide and iodine used concurrently against 3 bacterial and 16 yeast species. RESULTS: Synergistic or additive inhibitory effects were shown for hydrogen peroxide and iodine mixtures against all 19 species used in the study. Both biocides were mostly cidal individually and in mixtures against Pseudomonas aeruginosa and Staphylococcus aureus. Both compounds manifested static inhibitory effects individually, but their mixtures were synergistically cidal for Saccharomyces cerevisiae and Escherihia coli. Cells of S. cerevisiae treated with hydrogen peroxide and iodine-hydrogen peroxide mixture produced increased numbers of respiratory deficient mutants indicating genotoxic effects. CONCLUSION: Iodine and hydrogen peroxide used concurrently interact synergistically or additively against a range of prokaryotic and eukaryotic microorganisms. The study provides an insight as to how these traditional antimicrobials could be used more effectively for disinfection and antisepsis. In addition, a simple approach is proposed for scoring genotoxicity of different biocides by using the budding yeast system

An in vitro collagen perfusion wound biofilm model; with applications for antimicrobial studies and microbial metabolomics

BackgroundThe majority of in vitro studies of medically relevant biofilms involve the development of biofilm on an inanimate solid surface. However, infection in vivo consists of biofilm growth on, or suspended within, the semi-solid matrix of the tissue, whereby current models do not effectively simulate the nature of the in vivo environment. This paper describes development of an in vitro method for culturing wound associated microorganisms in a system that combines a semi-solid collagen gel matrix with continuous flow of simulated wound fluid. This enables culture of wound associated reproducible steady state biofilms under conditions that more closely simulate the dynamic wound environment. To demonstrate the use of this model the antimicrobial kinetics of ceftazidime, against both mature and developing Pseudomonas aeruginosa biofilms, was assessed. In addition, we have shown the potential application of this model system for investigating microbial metabolomics by employing selected ion flow tube mass spectrometry (SIFT-MS) to monitor ammonia and hydrogen cyanide production by Pseudomonas aeruginosa biofilms in real-time. ResultsThe collagen wound biofilm model facilitates growth of steady-state reproducible Pseudomonas aeruginosa biofilms under wound like conditions. A maximum biofilm density of 1010 cfu slide-1 was achieved by 30 hours of continuous culture and maintained throughout the remainder of the experiment. Treatment with ceftazidime at a clinically relevant dose resulted in a 1.2 – 1.6 log reduction in biofilm density at 72 hours compared to untreated controls. Treatment resulted in loss of complex biofilm architecture and morphological changes to bacterial cells, visualised using confocal microscopy. When monitoring the biofilms using SIFT-MS, ammonia and hydrogen cyanide levels peaked at 12 hours at 2273 ppb (±826.4) and 138 ppb (±49.1) respectively and were detectable throughout experimentation. ConclusionsThe collagen wound biofilm model has been developed to facilitate growth of reproducible biofilms under wound-like conditions. We have successfully used this method to: (1) evaluate antimicrobial efficacy and kinetics, clearly demonstrating the development of antimicrobial tolerance in biofilm cultures; (2) characterise volatile metabolite production by P. aeruginosa biofilms, demonstrating the potential use of this method in metabolomics studies

Wound dressings for a proteolytic-rich environment

Wound dressings have experienced continuous and significant changes over the years based on the knowledge of the biochemical events associated with chronic wounds. The development goes from natural materials used to just cover and conceal the wound to interactive materials that can facilitate the healing process, addressing specific issues in non-healing wounds. These new types of dressings often relate with the proteolytic wound environment and the bacteria load to enhance the healing. Recently, the wound dressing research is focusing on the replacement of synthetic polymers by natural protein materials to delivery bioactive agents to the wounds. This article provides an overview on the novel protein-based wound dressings such as silk fibroin keratin and elastin. The improved properties of these dressings, like the release of antibiotics and growth factors, are discussed. The different types of wounds and the effective parameters of healing process will be reviewed

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS