The variation of anticoagulation prescribed in foot and ankle surgery in the UK - UK foot and ankle thrombo-embolism audit (UK-FATE).

INTRODUCTION: Venous thrombo-embolism (VTE) is a recognised complication of foot and ankle surgery. There are multiple possible anticoagulation treatments available in the UK to mitigate the risk of developing VTE. Our primary objective was to assess the variability of chemical anticoagulation prescribed in patients undergoing foot and ankle procedures. METHODS: This was a UK-based national, multicenter, prospective audit spanning a collection duration of 9 months on all foot and ankle procedures, carried out in 68 UK centers between 1st June 2022 and 30th November 2022, with a further 3-month follow up period. All patients who underwent a foot and ankle surgical procedure (including Achilles tendon rupture treatment) were included in this study. RESULTS: Data on a total of 13,569 patients was submitted. Following data cleansing, 11,363 patients were available for further analysis, with anticoagulation data available for 11,099 patients. There were eleven different chemical anticoagulation treatments recorded across the cohort. A total of 3630 (31.95 %) patients received no chemical anticoagulation. The patients receiving chemical anticoagulation medication could be split into 4 main groups. The most common chemical anticoagulation received was low molecular weight heparin (LMWH) (6303, 84.4 % of patients receiving chemical anticoagulation). Aspirin was given in 4.1 % (308 patients), a Factor Xa inhibitor in 10 % (744 patients) and other anticoagulants (e.g. Warfarin) in 1.5 % (114 patients). The overall VTE rate in this sub analysis of patients receiving chemical anticoagulation, was 1.1 % (83 cases out of 7469). There was no significant difference seen in incidence of VTE between types of anticoagulants, when confounding factors were considered. The duration of post-operative chemical prophylaxis used by participants for most chemical anticoagulants was 6 weeks (64.50 %). CONCLUSION: There was significant variability of chemical anticoagulants reported in the study, with five different categories of anticoagulants used (including no chemical anticoagulation), and none clearly superior/inferior. The duration of anticoagulation was consistent across types of thromboprophylaxis.

Flocculating and dewatering of lake sediment: An in-situ pilot study comparing synthetic polymers and biopolymers for restoring lake water quality and reusing phosphorus.

Dredging of lake sediment is a method to remove accumulated phosphorus and nitrogen in lakes and thereby reducing the risk of eutrophication. After dredging, the sediment is dewatered to reduce the volume. It is important to get a high dry matter content and ensure that the filtrate does not contain harmful compounds so it can be returned to the lake. A pilot-scale belt filter and flexible intermediate bulk containers (FIBC) were used for dewatering lake sediment with the sediment treated with a synthetic polymer or three different biopolymers. The goal of the study was to retain the phosphorus in the filter cake while returning the filtrate to the lake with a minimal phosphorus content. Results showed dry matter content of up to 16 % in the dewatered sediment and the sediment retained 96-99 % of the phosphorus. Furthermore, nitrogen was reduced by 27-71 % in the filtrate water. Toxicity tests found low ecotoxicity for most biopolymer filtrates, whereas synthetic polymer showed the highest potential ecotoxicity. Consequently, biopolymers provided satisfactory results, proving more environmentally friendly despite requiring longer filtration time.

Incorporation of patient and public involvement in statistical methodology research: development of an animation.

BACKGROUND: Patient and Public Involvement and Engagement (PPIE) is important to all aspects of health research. However, there are few examples of successful PPIE in statistical methodology research. One of the reasons for this relates to challenges in the identification of individuals interested in statistical methodology research projects, and ambiguities over the importance of PPIE to these projects. METHODS: This project was conducted between August 2022 and August 2023. The aim is to report the process of the development of an accessible animation to describe what statistical methodology is and the importance of PPIE in statistical methodology research projects. For this, we combined storyboarding and scriptwriting with feedback from PPIE members and researchers. RESULTS: After three stages that incorporated feedback from the relevant stakeholders, we produced a final animation about PPIE in statistical methodology. The resulting animation used minimal text, simple animation techniques and was of short duration (< 3 min) to optimise the communication of the key messages clearly and effectively. CONCLUSIONS: The resulting animation provides a starting point for members of the public to learn about PPIE in statistical methodology research and for methodologists who wish to conduct PPIE. We recommend further work to explore ways in which members of the public can be more meaningfully involved in methodology research.

Patient and public involvement and engagement (PPIE) is when members of the public are directly involved in carrying out research projects. This is important because we as researchers want to make sure we are focusing on what matters most to patients, so that the research has as large an impact as possible. PPIE has typically been used in more applied research projects, such as clinical trials, but is equally as important in statistical methodology research, where we focus on making sure the statistical tools that we use in the applied projects are as good as possible. The aim of this project was to create a short animation that helps to explain the importance of PPIE in statistical methodology research projects. Researchers sometimes incorrectly assume that PPIE is less important in these projects as this type of research has a less obvious benefit to patients. The animation helps to further explain these concepts. It describes what statistical methodology research is and why involving members of the public is still important. This paper explains the process of developing the animation, including receiving feedback from members of the public to make sure the animation is accessible to as many people as possible. The result is a short, 3-min animation that is free to view on the NIHR website. This can be used by other researchers to help them when recruiting members of the public to their research projects.

Generating high-fidelity synthetic time-to-event datasets to improve data transparency and accessibility.

BACKGROUND: A lack of available data and statistical code being published alongside journal articles provides a significant barrier to open scientific discourse, and reproducibility of research. Information governance restrictions inhibit the active dissemination of individual level data to accompany published manuscripts. Realistic, high-fidelity time-to-event synthetic data can aid in the acceleration of methodological developments in survival analysis and beyond by enabling researchers to access and test published methods using data similar to that which they were developed on. METHODS: We present methods to accurately emulate the covariate patterns and survival times found in real-world datasets using synthetic data techniques, without compromising patient privacy. We model the joint covariate distribution of the original data using covariate specific sequential conditional regression models, then fit a complex flexible parametric survival model from which to generate survival times conditional on individual covariate patterns. We recreate the administrative censoring mechanism using the last observed follow-up date information from the initial dataset. Metrics for evaluating the accuracy of the synthetic data, and the non-identifiability of individuals from the original dataset, are presented. RESULTS: We successfully create a synthetic version of an example colon cancer dataset consisting of 9064 patients which aims to show good similarity to both covariate distributions and survival times from the original data, without containing any exact information from the original data, therefore allowing them to be published openly alongside research. CONCLUSIONS: We evaluate the effectiveness of the methods for constructing synthetic data, as well as providing evidence that there is minimal risk that a given patient from the original data could be identified from their individual unique patient information. Synthetic datasets using this methodology could be made available alongside published research without breaching data privacy protocols, and allow for data and code to be made available alongside methodological or applied manuscripts to greatly improve the transparency and accessibility of medical research.

Understanding the impact of sex and stage differences on melanoma cancer patient survival: a SEER-based study.

BACKGROUND: This paper investigates the difference in survival of melanoma patients across stage and sex by utilising net survival measures. Metrics are presented at both the individual and population level. METHODS: Flexible parametric models were fitted to estimate life-expectancy metrics to be applied to a group of 104,938 subjects with a melanoma skin cancer diagnosis from 2000 to 2017. Period analysis was used for better predictions for newly diagnosed patients, and missing-stage information was imputed for 9918 patients. Female relative survival was assigned to male subjects to demonstrate the survival discrepancies experienced between sexes. RESULTS: At the age of 60, males diagnosed at the regional stage lose an average of 4.99 years of life compared to the general population, and females lose 4.79 years, demonstrating the sex variation in expected mortality. In 2017, males contributed 3545 more life years lost than females, and a potential 1931 life years could be preserved if sex differences in survival were eliminated. CONCLUSIONS: This study demonstrates the survival differences across population subgroups as a result of a melanoma cancer diagnosis. Females experience better prognosis across age and stage at diagnosis; however, further investigation is necessary to better understand the mechanisms behind this difference.

Neurons with Complex Karyotypes Are Rare in Aged Human Neocortex.

A subset of human neocortical neurons harbors complex karyotypes wherein megabase-scale copy-number variants (CNVs) alter allelic diversity. Divergent levels of neurons with complex karyotypes (CNV neurons) are reported in different individuals, yet genome-wide and familial studies implicitly assume a single brain genome when assessing the genetic risk architecture of neurological disease. We assembled a brain CNV atlas using a robust computational approach applied to a new dataset (>800 neurons from 5 neurotypical individuals) and to published data from 10 additional neurotypical individuals. The atlas reveals that the frequency of neocortical neurons with complex karyotypes varies widely among individuals, but this variability is not readily accounted for by tissue quality or CNV detection approach. Rather, the age of the individual is anti-correlated with CNV neuron frequency. Fewer CNV neurons are observed in aged individuals than in young individuals.