Dressings and topical agents for arterial leg ulcers

Background: It is estimated that up to 1% of people in high-income countries suffer from a leg ulcer at some time in their life. The majority of leg ulcers are associated with circulation problems; poor blood return in the veins causes venous ulcers (around 70% of ulcers) and poor blood supply to the legs causes arterial ulcers (around 22% of ulcers). Treatment of arterial leg ulcers is directed towards correcting poor arterial blood supply, for example by correcting arterial blockages (either surgically or pharmaceutically). If the blood supply has been restored, these arterial ulcers can heal following principles of good wound-care. Dressings and topical agents make up a part of good wound-care for arterial ulcers, but there are many products available, and it is unclear what impact these have on ulcer healing. This is the third update of a review first published in 2003. Objectives: To determine whether topical agents and wound dressings affect healing in arterial ulcers. To compare healing rates and patient-centred outcomes between wound dressings and topical agents. Search methods: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature and Allied and Complementary Medicine databases, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials register to 28 January 2019. Selection criteria: Randomised controlled trials (RCTs), or controlled clinical trials (CCTs) evaluating dressings and topical agents in the treatment of arterial leg ulcers were eligible for inclusion. We included participants with arterial leg ulcers irrespective of method of diagnosis. Trials that included participants with mixed arterio-venous disease and diabetes were eligible for inclusion if they presented results separately for the different groups. All wound dressings and topical agents were eligible for inclusion in this review. We excluded trials which did not report on at least one of the primary outcomes (time to healing, proportion completely healed, or change in ulcer area). Data collection and analysis: Two review authors independently extracted information on the participants' characteristics, the interventions, and outcomes using a standardised data extraction form. Review authors resolved any disagreements through discussion. We presented the data narratively due to differences in the included trials. We used GRADE to assess the certainty of the evidence. Main results: Two trials met the inclusion criteria. One compared 2% ketanserin ointment in polyethylene glycol (PEG) with PEG alone, used twice a day by 40 participants with arterial leg ulcers, for eight weeks or until healing, whichever was sooner. One compared topical application of blood-derived concentrated growth factor (CGF) with standard dressing (polyurethane film or foam); both applied weekly for six weeks by 61 participants with non-healing ulcers (venous, diabetic arterial, neuropathic, traumatic, or vasculitic). Both trials were small, reported results inadequately, and were of low methodological quality. Short follow-up times (six and eight weeks) meant it would be difficult to capture sufficient healing events to allow us to make comparisons between treatments. One trial demonstrated accelerated wound healing in the ketanserin group compared with the control group. In the trial that compared CGF with standard dressings, the number of participants with diabetic arterial ulcers were only reported in the CGF group (9/31), and the number of participants with diabetic arterial ulcers and their data were not reported separately for the standard dressing group. In the CGF group, 66.6% (6/9) of diabetic arterial ulcers showed more than a 50% decrease in ulcer size compared to 6.7% (2/30) of non-healing ulcers treated with standard dressing. We assessed this as very-low certainty evidence due to the small number of studies and arterial ulcer participants, inadequate reporting of methodology and data, and short follow-up period. Only one trial reported side effects (complications), stating that no participant experienced these during follow-up (six weeks, low-certainty evidence). It should also be noted that ketanserin is not licensed in all countries for use in humans. Neither study reported time to ulcer healing, patient satisfaction or quality of life. Authors' conclusions: There is insufficient evidence to determine whether the choice of topical agent or dressing affects the healing of arterial leg ulcers

Exploring the moral imagination through relational pedagogies in pre-service teacher ethics

Whilst there is significant research examining the pedagogical development of pre-service teachers’ knowledge and skills after their internship experience, there has been little examination of their experience of ethical tension and little investigation into ways to further enhance pre-service teachers’ ethical reasoning. This paper documents some of the ways that pre-service teachers reason about ethically charged situations. It aims to extend conceptions of the moral imagination and its place in the teaching of ethics to pre-service teachers by discussing findings from a teaching project pilot study designed to investigate the ways in which pre-service teachers experience and respond to ethical tensions. Whilst recognising common difficulties in responding to ethically charged situations, our analysis utilises pre-service teacher dialogue in the form of an assessment strategy based on a ‘community of inquiry’ model and examines the ways in which pre-service teachers utilise the moral imagination to reason through ethical issues. This paper indicates some ways professional development could provide opportunities more aligned with pre-service teachers’ learning needs in the development of their ethical reasoning, and argues that the moral imagination is a fundamental feature of ethical practice and decision-making

Questions of Value: Taking Museums into a High Security Prison

This research was developed as part of an AHRC Collaborative Doctoral Award, between the University of Leeds and Leeds Museums and Galleries. The central area for investigation was to establish the value to be gained from providing prisoners in a high security prison access to museum objects and activities inspired by them. The project itself was delivered to a group of prisoners in HMP Wakefield in 2012 over a twelve-week period. The four-stage project provided opportunities for different forms of interaction with the museum objects and culminated in a final exhibition of work created by the prisoner participants during the project. Throughout the project the findings were positive. They offer strong support to the idea that high security prisons can be viewed as a community in their own right where positive relationships can be established and negative stereotypes broken down. When looked at collectively, the findings indicate that participation in the project made both an immediate and longer-term impact on the wellbeing of those who participated. In some cases this also linked to a reduction in the fears associated with feeling institutionalised

Retinal vessel traits and their association with diabetic retinopathy and cognitive decline in a population with type 2 diabetes

Background People with diabetes are at an increased risk of developing vascular disease, which is the leading cause of morbidity and mortality in this population. The retina is one of the few places in the body that offers noninvasive visualisation of the vascular system and thus provides a rich platform to evaluate local and systemic vascular disease. Recent advancements in retinal image analysis tools allow us to evaluate the retinal microvasculature in a more efficient and unbiased way compared to manual methods. Local retinal changes may provide insight into vascular disease prior to overt pathological changes. Aim The aim of this thesis was to explore and evaluate retinal vessel traits in relation to various manifestations of vascular disease, specifically diabetic retinopathy and cognitive decline, using prospectively collected data. In addition to undertaking this research, this PhD project also aimed to contribute to the collection of primary data from in ongoing longitudinal cohort in order to provide data not only for this project, but for many other future and ongoing projects. Methods Edinburgh Type 2 Diabetes Study is a cohort of 1,066 adults aged 60-75 years with type 2 diabetes living in the Lothian region of Scotland. Data were collected through research clinics as well as record linkage. Diabetic retinopathy status was obtained from the national screening programme and to evaluate cognitive decline, dementia diagnosis was obtained from a combination of medical records, death records and self-report. Cognitive decline was also evaluated using cognitive status derived from a battery of cognitive tests administered at baseline and then again after 10 years. Retinal images were analysed using VAMPIRE software for central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), arteriolar and venular tortuosity, fractal dimension and density. Results A total of 83 participants (11.6%) developed retinopathy over 10 years. After controlling for a wide number of cardiometabolic, diabetic and vascular risk factors, there was evidence of an association between increased venular tortuosity and incident retinopathy (odds ratio (OR) 1.51, 95% confidence interval (CI) 1.15 to 1.98, p = 0.003), as well as decreased standardised fractal dimension and incident retinopathy (OR 0.75, 0.58 to 0.96, p = 0.025). Of the total 1066, 106 (9.9%) were determined to have a dementia diagnosis after 10 years of follow-up. Cognitive decline, as measured by cognitive testing after 10 years, controlling for baseline cognitive status, was measured in the 581 returning participants. There were no independent associations between the retinal vessel traits and cognitive decline, using either dementia or the general intelligence factor, after controlling for various covariates. There was, however, evidence of age-related decreases in fractal dimension and density over the course of the study. Conclusions This thesis has provided evidence from the ET2DS that venular tortuosity and fractal dimension are independently associated with diabetic retinopathy. The independent associations were modest and need to be contextualised within the heterogeneity that exists within the supporting literature as well as replicated in other studies, but they provide exciting support for the use of the retinal vessel traits in future risk prediction modelling for diabetic retinopathy. There was no evidence of an association between the reported retinal vessel traits and cognitive decline. Novel findings regarding age-related decreases in fractal dimension and density are important as more information is coming to light regarding the vessel traits and their associations with vascular disease

Effect of methotrexate/vitamin B12 on DNA methylation as a potential factor in leukemia treatment-related neurotoxicity

Methotrexate (MTX) is administered to treat childhood acute lymphoblastic leukemia (ALL). It acts by inhibiting dihydrofolate reductase which reduces methyltetrahydrofolate, a key component in one carbon metabolism, thus reducing cell proliferation. Further perturbations to one carbon metabolism, such as reduced Vitamin B12 levels via the use of nitrous oxide for sedation during childhood ALL treatment, may increase neurotoxicity risk. With B12 as an enzymatic cofactor, methyltetrahydrofolate is essential to produce methionine, which is critical for DNA methylation. We investigated global and gene specific DNA methylation in neuronal cell lines in response to MTX treatment and Vitamin B12 concentration individually, and in combination. Results: MTX treatment alone significantly increased LINE-1 methylation in SH-SY5Y (p = 0.040) and DAOY (p < 0.001), and increased FKBP5 methylation in MO3.13 cells (p = 0.009). Conclusion: We conclude that altered DNA methylation of brain/central nervous system cells could be one mechanism involved in MTX treatment-related neurotoxicities and neurocognitive late effects in ALL survivors

Association between medical androgen deprivation therapy and long-term cardiovascular disease and all-cause mortality in nonmetastatic prostate cancer

Studies have suggested that prostate cancer (PCa) patients receiving androgen deprivation therapy (ADT) are at increased risk of developing or exacerbating cardiovascular disease (CVD). We aimed to explore the association between ADT for PCa and subsequent CVD and all-cause mortality in this nationwide, longitudinal study. We also evaluated the role of cardiovascular risk and ADT duration to determine effect modification. Norwegian registry data were used to identify patients with PCa from 2008-18 and who received primary ADT in the first year after diagnosis. The associations between ADT and composite cardiovascular events, and the individual components of myocardial infarction, stroke and heart failure, in addition to atrial fibrillation and all-cause mortality, were explored using time-varying Cox regression models. We included 30 923 PCa patients, of whom 8449 (27%) received primary ADT. Mean follow-up was 2.9 and 3.8 years for CVD events and mortality, respectively. We found an association between ADT and composite CVD (adjusted HR 1.13: 95% CI 1.05-1.21), myocardial infarction (1.18: 1.05-1.32), stroke (1.21: 1.06-1.38), heart failure (1.23: 1.13-1.35) and all-cause mortality (1.49: 1.39-1.61). These associations persisted in those with low and moderate CVD risk and ADT longer than 7 months. A relationship between ADT and composite CVD and all-cause mortality was observed, especially in those with moderate CVD risk and longer treatment duration. Future studies with more detailed cancer data are needed to verify the clinical relevance of these results, especially when considering all-cause mortality within the context of treatment guidelines and benefits of ADT.publishedVersio

Evidence of a common understanding of proximate and distal drivers of reef health

Marine management has typically prioritised natural science methodological traditions as an evidence base for decision-making; yet better integration of social science methods are increasingly shown to provide a more comprehensive picture to base management decisions. Specifically, perceptions-based assessments are gaining support, as they can provide efficient and holistic evaluation regarding management issues. This study focuses on coral reefs because they are particularly threatened ecosystems, due to their ecological complexity, socio-economic importance, and the range of environmental drivers that impact them. Research has largely concentrated on assessing proximate threats to coral reefs. Less attention has been given to distal drivers, such as socio-economic and governance factors. A common understanding of threats related to coral reef degradation is critical for integrated management that takes account of peoples’ concerns. This study compares perceptions of drivers of reef health among stakeholders (n = 110) across different sectors and governance levels, in four Caribbean countries. Interview data identified 37 proximate and 136 distal drivers, categorised into 27 themes. Five sub-groups of themes connecting proximate and distal drivers were identified. Perceptions of two of these narratives, relating to ‘fishing and socioeconomic issues’ and ‘reef management and coastal development’, differed among respondents from different countries and sectors respectively. However, the findings highlight a shared perception of many themes, with 18 of the 27 (67%) mentioned by > 25% of respondents. This paper highlights the application of perceptions data for marine management, demonstrating how knowledge of proximate and distal drivers can be applied to identify important issues at different context-specific scales

Home versus in-patient treatment for deep vein thrombosis

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