Understanding cost-utility analysis studies in the trauma and orthopaedic surgery literature.

Cost-utility analysis (CUA) studies are becoming increasingly important due to the need to reduce healthcare spending, especially in the field of trauma and orthopaedics.There is an increasing need for trauma and orthopaedic surgeons to understand these economic evaluations to ensure informed cost-effective decisions can be made to benefit the patient and funding body.This review discusses the fundamental principles required to understand CUA studies in the literature, including a discussion of the different methods employed to assess the health outcomes associated with different management options and the various approaches used to calculate the costs involved.Different types of model design may be used to conduct a CUA which can be broadly categorized into real-life clinical studies and computer-simulated modelling. We discuss the main types of study designs used within each category. We also cover the different types of sensitivity analysis used to quantify uncertainty in these studies and the commonly employed instruments used to assess the quality of CUAs. Finally, we discuss some of the important limitations of CUAs that need to be considered.This review outlines the main concepts required to understand the CUA literature and provides a basic framework for their future conduct. Cite this article: EFORT Open Rev 2021;6:305-315. DOI: 10.1302/2058-5241.6.200115

Cryopreservation of Human Adipose Tissues and Adipose-Derived Stem Cells with DMSO and/or Trehalose: A Systematic Review.

Adipose tissue senescence is implicated as a major player in obesity- and ageing-related disorders. There is a growing body of research studying relevant mechanisms in age-related diseases, as well as the use of adipose-derived stem cells in regenerative medicine. The cell banking of tissue by utilising cryopreservation would allow for much greater flexibility of use. Dimethyl sulfoxide (DMSO) is the most commonly used cryopreservative agent but is toxic to cells. Trehalose is a sugar synthesised by lower organisms to withstand extreme cold and drought that has been trialled as a cryopreservative agent. To examine the efficacy of trehalose in the cryopreservation of human adipose tissue, we conducted a systematic review of studies that used trehalose for the cryopreservation of human adipose tissues and adipose-derived stem cells. Thirteen articles, including fourteen studies, were included in the final review. All seven studies that examined DMSO and trehalose showed that they could be combined effectively to cryopreserve adipocytes. Although studies that compared nonpermeable trehalose with DMSO found trehalose to be inferior, studies that devised methods to deliver nonpermeable trehalose into the cell found it comparable to DMSO. Trehalose is only comparable to DMSO when methods are devised to introduce it into the cell. There is some evidence to support using trehalose instead of using no cryopreservative agent

Innovation Pathways in the NHS: An Introductory Review

Abstract: Healthcare as an industry is recognised as one of the most innovative. Despite heavy regulation, there is substantial scope for new technologies and care models to not only boost patient outcomes but to do so at reduced cost to healthcare systems and consumers. Promoting innovation within national health systems such as the National Health Service (NHS) in the United Kingdom (UK) has been set as a key target for health care professionals and policy makers. However, while the UK has a world-class biomedical research industry, several reports in the last twenty years have highlighted the difficulties faced by the NHS in encouraging and adopting innovations, with the journey from idea to implementation of health technology often taking years and being very expensive, with a high failure rate. This has led to the establishment of several innovation pathways within and around the NHS, to encourage the invention, development and implementation of cost-effective technologies that improve health care delivery. These pathways span local, regional and national health infrastructure. They operate at different stages of the innovation pipeline, with their scope and work defined by location, technology area or industry sector, based on the specific problem identified when they were set up. In this introductory review, we outline each of the major innovation pathways operating at local, regional and national levels across the NHS, including their history, governance, operating procedures and areas of expertise. The extent to which innovation pathways address current challenges faced by innovators is discussed, as well as areas for improvement and future study

Mesenchymal stem cell therapy in hypertrophic and keloid scars.

Funder: University of CambridgeScars are the normal outcome of wound repair and involve a co-ordinated inflammatory and fibrotic process. When a scar does not resolve, uncontrolled chronic inflammation can persist and elicits excessive scarring that leads to a range of abnormal phenotypes such as hypertrophic and keloid scars. These pathologies result in significant impairment of quality of life over a long period of time. Existing treatment options are generally unsatisfactory, and there is mounting interest in innovative cell-based therapies. Despite the interest in mesenchymal stem cells (MSCs), there is yet to be a human clinical trial that investigates the potential of MSCs in treating abnormal scarring. A synthesis of existing evidence of animal studies may therefore provide insight into the barriers to human application. The aim of this PRISMA systematic review was to evaluate the effectiveness of MSC transplantation in the treatment of hypertrophic and keloid scars in in vivo models. A total of 11 case-control studies were identified that treated a total of 156 subjects with MSCs or MSC-conditioned media. Ten studies assessed hypertrophic scars, and one looked at keloid scars. All studies evaluated scars in terms of macroscopic and histological appearances and most incorporated immunohistochemistry. The included studies all found improvements in the above outcomes with MSC or MSC-conditioned media without complications. The studies reviewed support a role for MSC therapy in treating scars that needs further exploration. The transferability of these findings to humans is limited by factors such as the reliability and validity of the disease model, the need to identify the optimal MSC cell source, and the outcome measures employed

Insights into patient preferences for elective surgery during the COVID-19 pandemic.

AIMS: To investigate factors that contribute to patient decisions regarding attendance for arthroplasty during the COVID-19 pandemic. METHODS: A postal questionnaire was distributed to patients on the waiting list for hip or knee arthroplasty in a single tertiary centre within the UK. Patient factors that may have influenced the decision to attend for arthroplasty, global quality of life (QoL) (EuroQol five-dimension three-level (EQ-5D-3L)), and joint-specific QoL (Oxford Hip or Knee Score) were assessed. Patients were asked at which 'COVID-alert' level they would be willing to attend an NHS and a "COVID-light" hospital for arthroplasty. Independent predictors were assessed using multivariate logistic regression. RESULTS: Of 540 distributed questionnaires, 400 (74.1%; 236 awaiting hip arthroplasty, 164 awaiting knee arthroplasty) complete responses were received and included. Less than half (48.2%) were willing to attend for hip or knee arthroplasty while a UK COVID-19 epidemic was in circulation (COVID-alert levels 3 to 5). Patients with worse joint-specific QoL had a preference to proceed with surgery at COVID-alert levels 3 to 5 compared to levels 1 and 2 (hip arthroplasty odds ratio (OR) 1.54 (95% confidence interval (CI) 1.45 to 1.63); knee arthroplasty OR 1.16 (1.07 to 1.26)). The odds of patients with worse joint-specific QoL being willing to attend for surgery at COVID-alert levels 3 to 5 increased further if surgery in a private, "COVID-light" hospital was available (hip arthroplasty OR 3.50 (95% CI 3.26 to 3.71); knee arthroplasty OR 1.41 (95% CI 1.29 to 1.53). CONCLUSION: Patient decisions surrounding elective surgery have been influenced by the global COVID-19 pandemic, highlighting the importance of patient involvement in ensuring optimized provision of elective surgery during these challenging times. Cite this article: Bone Jt Open 2021;2(4):261-270

Axial Globe Position Measurement: A Prospective Multicenter Study by the International Thyroid Eye Disease Society

Identify a reproducible measure of axial globe position (AGP) for multicenter studies on patients with thyroid eye disease (TED)

Systematic Identification of Factors for Provirus Silencing in Embryonic Stem Cells

Embryonic stem cells (ESCs) repress the expression of exogenous proviruses and endogenous retroviruses (ERVs). Here, we systematically dissected the cellular factors involved in provirus repression in embryonic carcinomas (ECs) and ESCs by a genome-wide siRNA screen. Histone chaperones (Chaf1a/b), sumoylation factors (Sumo2/Ube2i/Sae1/Uba2/Senp6), and chromatin modifiers (Trim28/Eset/Atf7ip) are key determinants that establish provirus silencing. RNA-seq analysis uncovered the roles of Chaf1a/b and sumoylation modifiers in the repression of ERVs. ChIP-seq analysis demonstrates direct recruitment of Chaf1a and Sumo2 to ERVs. Chaf1a reinforces transcriptional repression via its interaction with members of the NuRD complex (Kdm1a, Hdac1/2) and Eset, while Sumo2 orchestrates the provirus repressive function of the canonical Zfp809/Trim28/Eset machinery by sumoylation of Trim28. Our study reports a genome-wide atlas of functional nodes that mediate proviral silencing in ESCs and illuminates the comprehensive, interconnected, and multi-layered genetic and epigenetic mechanisms by which ESCs repress retroviruses within the genome

Chemically-synthesised, atomically-precise gold clusters deposited and activated on titania

Synchrotron XPS was used to investigate a series of chemically-synthesised, atomically-precise gold clusters Au(n)(PPh₃)(y) (n = 8, 9, 11 and 101, with y depending on cluster size) immobilized on titania nanoparticles. The gold clusters were washed with toluene at 100 °C or calcined at 200 °C to remove the organic ligand. From the position of the Au 4f₇/₂ peak it is concluded that cluster size is not altered through the deposition. From the analysis of the phosphorous spectra, it can be concluded that the applied heat treatment removes the organic ligands. Washing and calcination leads to partial oxidation and partial agglomeration of the clusters. Oxidation of the clusters is most likely due to the interaction of the cluster core with the oxygen of the titania surface after removal of ligands. The position of the Au 4f₇/₂ peak indicates that the size of the agglomerated clusters is still smaller than that of Au₁₀₁.David P. Anderson, Jason F. Alvino, Alexander Gentleman, Hassan Al Qahtani, Lars Thomsen, Matthew I. J. Polson, Gregory F. Metha, Vladimir B. Golovko and Gunther G. Andersso

The Airborne Metagenome in an Indoor Urban Environment

The indoor atmosphere is an ecological unit that impacts on public health. To investigate the composition of organisms in this space, we applied culture-independent approaches to microbes harvested from the air of two densely populated urban buildings, from which we analyzed 80 megabases genomic DNA sequence and 6000 16S rDNA clones. The air microbiota is primarily bacteria, including potential opportunistic pathogens commonly isolated from human-inhabited environments such as hospitals, but none of the data contain matches to virulent pathogens or bioterror agents. Comparison of air samples with each other and nearby environments suggested that the indoor air microbes are not random transients from surrounding outdoor environments, but rather originate from indoor niches. Sequence annotation by gene function revealed specific adaptive capabilities enriched in the air environment, including genes potentially involved in resistance to desiccation and oxidative damage. This baseline index of air microbiota will be valuable for improving designs of surveillance for natural or man-made release of virulent pathogens