A study of the complications associated with haemodialysis vascular access in patients with renal failure

Successful haemodialysis depends on the availability of safe, efficient, and durable access to the vascular tree. This can be provided by creation of an arteriovenous fistula, insertion of a synthetic vascular graft or insertion of a central venous catheter. Established haemodialysis vascular access is associated with a number of important complications which can impact significantly on both the quality of life and survival of haemodialysis patients. The primary aim of this thesis was to perform a detailed evaluation of the risks to health conferred by haemodialysis vascular access and its maintenance in patients with advanced renal failure. The work described in this thesis describes the relative strength and independence of association between haemodialysis vascular access type and risk of mortality, bacteraemia and catheter thrombosis. Greater clarity is demonstrated on the relative effect of heparin-based haemodialysis catheter lock solutions on markers of systemic coagulation in vivo, whilst the in-vitro variability of antimicrobial activity against planktonic and biofilm-embedded staphylococci achieved with catheter lock solutions containing heparin and vancomycin, alone and in combination, is clearly shown. New insights are gained into the benefits of contrast magnetic resonance venography as a tool for demonstrating thrombosis and stenosis of the central veins in the assessment of vascular access in haemodialysis patients. Similarly, the emergence of a new disease, nephrogenic systemic fibrosis was found and its association with gadolinium-enhanced magnetic resonance imaging was explored in detail

Developing and evaluating complex interventions: the new Medical Research Council guidance

<p><i>Evaluating complex interventions is complicated. The Medical Research Council's evaluation framework (2000) brought welcome clarity to the task. Now the council has updated its guidance</i></p> <p>Complex interventions are widely used in the health service, in public health practice, and in areas of social policy that have important health consequences, such as education, transport, and housing. They present various problems for evaluators, in addition to the practical and methodological difficulties that any successful evaluation must overcome. In 2000, the Medical Research Council (MRC) published a framework<sup>1</sup> to help researchers and research funders to recognise and adopt appropriate methods. The framework has been highly influential, and the accompanying BMJ paper is widely cited.<sup>2</sup> However, much valuable experience has since accumulated of both conventional and more innovative methods. This has now been incorporated in comprehensively revised and updated guidance recently released by the MRC (<a href="www.mrc.ac.uk/complexinterventionsguidance">www.mrc.ac.uk/complexinterventionsguidance</a>). In this article we summarise the issues that prompted the revision and the key messages of the new guidance. </p&gt

A national appraisal of haemodialysis vascular access provision in Scotland

Purpose: Published registry data demonstrate longstanding variation in the utilisation of different vascular access (VA) modalities between Scottish renal units; this may reflect different clinical processes between centres. A comprehensive appraisal was undertaken to understand the processes underpinning VA creation and maintenance across Scotland. Methods: A mixed methods approach was utilised. Fifty-two semi-structured interviews were conducted with patients and clinicians in all ten, adult and paediatric, Scottish renal units. Interview transcripts were subjected to thematic analysis. Clinical activity data were prospectively collected for six weeks, and correlated with registry data. Results: VA accounts for a large clinical workload. There was significant inter-centre variation in the utilisation of different VA modalities, and patients described frustrating, dissatisfying experiences. VA creation and maintenance pathways functioned best when nephrologists, surgeons and radiologists were co-located on the same campus with close multi-disciplinary working, protected clinical time, and proactive VA maintenance. No unit routinely measured or discussed procedure outcomes or strategic aspects of their service. Conclusions: Varied clinical outcomes reflected varied clinical processes. Optimised clinical pathways, staff education and measurement of clinical outcomes may improve VA service quality and facilitate safer, more effective, patient-centred care

Preserving the palaeoenvironmental record in Drylands: Bioturbation and its significance for luminescence-derived chronologies

Luminescence (OSL) dating has revolutionised the understanding of Late Pleistocene dryland activity. However, one of the key assumptions for this sort of palaeoenvironmental work is that sedimentary sequences have been preserved intact, enabling their use as proxy indicators of past changes. This relies on stabilisation or burial soon after deposition and a mechanism to prevent any subsequent re-mobilisation. As well as a dating technique OSL, especially at the single grain level, can be used to gain an insight into post-depositional processes that may distort or invalidate the palaeoenvironmental record of geological sediment sequences. This paper explores the possible impact of bioturbation (the movement of sediment by flora and fauna) on luminescence derived chronologies from Quaternary sedimentary deposits in Texas and Florida (USA) which have both independent radiocarbon chronologies and archaeological evidence. These sites clearly illustrate the ability of bioturbation to rejuvenate ancient weathered sandy bedrock and/or to alter depositional stratigraphies through the processes of exhumation and sub-surface mixing of sediment. The use of multiple OSL replicate measurements is advocated as a strategy for checking for bioturbated sediment. Where significant OSL heterogeneity is found, caution should be taken with the derived OSL ages and further measurements at the single grain level are recommended. Observations from the linear dunes of the Kalahari show them to have no bedding structure and to have OSL heterogeneity similar to that shown from the bioturbated Texan and Florida sites. The Kalahari linear dunes could have therefore undergone hitherto undetected post-depositional sediment disturbance which would have implications for the established OSL chronology for the region

COVID-19 in patients undergoing chronic kidney replacement therapy and kidney transplant recipients in Scotland: findings and experience from the Scottish Renal Registry

BackgroundInfection with the severe acute respiratory coronavirus 2 (SARS-CoV-2) has led to a worldwide pandemic with coronavirus disease 2019 (COVID-19), the disease caused by SARS-CoV-2, overwhelming healthcare systems globally. Preliminary reports suggest a high incidence of infection and mortality with SARS-CoV-2 in patients receiving kidney replacement therapy (KRT). The aims of this study are to report characteristics, rates and outcomes of all patients affected by infection with SARS-CoV-2 undergoing KRT in Scotland.MethodsStudy design was an observational cohort study. Data were linked between the Scottish Renal Registry, Health Protection Scotland and the Scottish Intensive Care Society Audit Group national data sets using a unique patient identifier (Community Health Index (CHI)) for each individual by the Public Health and Intelligence unit of Public Health, Scotland. Descriptive statistics and survival analyses were performed.Results During the period 1st March 2020 to 31st May 2020, 110 patients receiving KRT tested positive for SARS-CoV-2 amounting to 2% of the prevalent KRT population. Of those affected, 86 were receiving haemodialysis or peritoneal dialysis and 24 had a renal transplant. Patients who tested positive were older and more likely to reside in more deprived postcodes. Mortality was high at 26.7% in the dialysis patients and 29.2% in the transplant patients. ConclusionThe rate of detected SARS-CoV-2 in people receiving KRT in Scotland was relatively low but with a high mortality for those demonstrating infection. Although impossible to confirm, it appears that the measures taken within dialysis units coupled with the national shielding policy, have been effective in protecting this population from infection. <br/

The impact of vaccination on incidence and outcomes of SARS-CoV-2 infection in patients with kidney failure in Scotland

Background: Patients with kidney failure requiring kidney replacement therapy (KRT) are at high risk of complications and death following SARS-CoV-2 infection with variable antibody responses to vaccination reported. We investigated the effects of COVID-19 vaccination on incidence of infection, hospitalization and death of COVID-19 infection. Methods: Study design was an observational data linkage cohort study. Multiple healthcare datasets were linked to ascertain all SARS-CoV-2 testing, vaccination, hospitalization, and mortality data for all patients treated with KRT in Scotland, from the start of the pandemic over a period of 20 months. Descriptive statistics, survival analyses, and vaccine effectiveness were calculated. Results: As of 19th September 2021, 93% (n=5281) of the established KRT population in Scotland had received two doses of an approved SARS-CoV-2 vaccine. Over the study period, there were 814 cases of SARS-CoV-2 infection (15.1% of the KRT population). Vaccine effectiveness against infection and hospitalization was 33% (95% CI 0-52) and 38% (95% CI 0-57) respectively. 9.2% of fully vaccinated individuals died within 28 days of a SARS-CoV-2 positive PCR test (7% dialysis patients and 10% kidney transplant recipients). This compares to &lt;0.1% of the vaccinated Scottish population being admitted to hospital or dying death due to COVID19 during that period. Conclusions: These data demonstrate a primary vaccine course of two doses has limited impact on COVID-19 infection and its complications in patients treated with KRT. Adjunctive strategies to reduce risk of both COVID-19 infection and its complications in this population are urgently required

Mental health and health behaviours before and during the initial phase of the COVID-19 lockdown: longitudinal analyses of the UK Household Longitudinal Study.

Background There are concerns that COVID-19 mitigation measures, including the ‘lockdown’, may have unintended health consequences. We examined trends in mental health and health behaviours in the UK before and during the initial phase of the COVID-19 lockdown and differences across population subgroups. Methods Repeated cross-sectional and longitudinal analysis of the UK Household Longitudinal Study, including representative samples of over 27,000 adults (aged 18+) interviewed in four survey waves between 2015 and 2020. A total of 9748 adults had complete data for longitudinal analyses. Outcomes included psychological distress (General Health Questionnaire-12), loneliness, current cigarette smoking, use of e-cigarettes and alcohol consumption. Cross-sectional prevalence estimates were calculated and multilevel Poisson regression assessed associations between time period and the outcomes of interest, as well as differential associations by age, gender, education level and ethnicity. Results Psychological distress increased 1 month into lockdown with the prevalence rising from 19.4% (95% CI 18.7% to 20.1%) in 2017–2019 to 30.6% (95% CI 29.1% to 32.3%) in April 2020 (RR=1.3, 95% CI 1.2 to 1.4). Groups most adversely affected included women, young adults, people from an Asian background and those who were degree educated. Loneliness remained stable overall (RR=0.9, 95% CI 0.6 to 1.5). Smoking declined (RR=0.9, 95% CI=0.8,1.0) and the proportion of people drinking four or more times per week increased (RR=1.4, 95% CI 1.3 to 1.5), as did binge drinking (RR=1.5, 95% CI 1.3 to 1.7). Conclusions Psychological distress increased 1 month into lockdown, particularly among women and young adults. Smoking declined, but adverse alcohol use generally increased. Effective measures are required to mitigate negative impacts on health

Antitumour Activity of the Novel Flavonoid Oncamex in Preclinical Breast Cancer Models

We thank SULSA (Scottish Universities Life Science Alliance) for supporting this project through a SULSA BioSkape Industry PhD Studentship and Antoxis Limited for providing additional funding. We also thank the 7th Framework Programme of the European Union (METOXIA project; HEALTH-F2-2009-222741) for support.Background: The natural polyphenol myricetin induces cell cycle arrest and apoptosis in preclinical cancer models. We hypothesised that myricetin-derived flavonoids with enhanced redox properties, improved cell uptake and mitochondrial targeting might have increased potential as antitumour agents. Methods: We studied the effect of a second-generation flavonoid analogue, Oncamex, in a panel of 7 breast cancer cell lines, applying western blotting, gene expression analysis, fluorescence microscopy, and immunohistochemistry to xenograft tissue to investigate its mechanism of action. Results: Proliferation assays showed that Oncamex: treatment for 8 h reduced cell viability and induced cytotoxicity and apoptosis, concomitant with increased caspase activation. Microarray analysis showed that Oncamex was associated with changes in expression of genes controlling cell cycle and apoptosis . Fluorescence microscopy showed the compound’s mitochondrial targeting and ROS-modulating properties, inducing superoxide production at concentrations associated with anti-proliferative effects. A preliminary in vivo study in mice implanted with the MDA-MB-231 breast cancer xenograft showed that Oncamex inhibited tumour growth, reduced tissue viability and Ki-67 proliferation, with no overall systemic toxicity. Conclusion: Oncamex is a novel flavonoid capable of specific mitochondrial delivery and redox modulation. It has shown antitumour activity in preclinical models of breast cancer, supporting the potential of this prototypic candidate for its continued development as an anticancer agent.Publisher PDFPeer reviewe

Acute involution in the tammar wallaby : identification of genes and putative novel milk proteins implicated in mammary gland function

AbstractMarsupials provide a suitable alternative model to studying mammary gland involution. They have evolved a different reproductive strategy from eutherians, giving birth to an altricial young and secreting milk that changes in composition during lactation. In this study, we used a marsupial-specific EST microarray to identify 47 up-regulated genes during mammary gland involution in the tammar wallaby (Macropus eugenii). These include the pro-apoptotic tumour necrosis factor receptor superfamily 21 (TNFRSF21) gene, whose expression in the mammary gland has not previously been reported. Genes encoding putative novel milk proteins which may protect the mammary gland from infection were also found to be up-regulated, such as amiloride binding protein 1 (ABP1), complement component 1QB (C1QB), complement component 4A (C4A) and colony stimulating factor 2 receptor β (CSF2Rβ). Our results show that the marsupial reproductive strategy was successfully exploited to identify genes and putative novel milk proteins implicated in mammary gland involution