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Introduction: IgA vasculitis (IgAV, Henoch-Schönlein purpura, HSP) is the most common vasculitis of childhood and currently contributes to 1-2% of all chronic kidney disease (CKD) stage 5. New methods of measuring disease activity are required to improve the standard of care given. The aim of this thesis is to evaluate methods of measuring disease activity in IgAV using urine biomarkers and a disease-specific scoring tool. Methods: Firstly, a systematic literature review was performed using 4 search engines and a search term strategy with predefined inclusion and exclusion criteria. Promising biomarkers were divided in terms of traditional or novel and described using statistical significance and area under the curve (AUC) values. Secondly, a specific disease activity scoring tool (the IgA-VAS) was developed and preliminarily validated in a cohort of paediatric patients with IgAV. Test validity, concurrent validity and inter-rater agreement were assessed retrospectively. A randomly selected subgroup were also scored using a visual analogue scale. Results: The systematic review identified 13 eligible studies. A total of 2,446 paediatric patients were included: healthy controls (n=761), children with IgAV-N (n=1,236) and children with IgAV without nephritis (IgAV-noN, n=449). 51% were male, median age 7.9 years. The traditional markers, 24-hour protein quantity and urine protein:creatinine ratio were deemed acceptable for assessing severity of nephritis (AUC 0.5, p

Background Cystic fibrosis-related diabetes (CFRD) is the most common comorbidity found in people with cystic fibrosis (pwCF). CFRD is associated with increased adverse outcomes and burden of treatment in pwCF as well as reduced quality of life. People with CFRD (pwCFRD) must measure their blood glucose levels several times per day to monitor their diabetes and so that treatment can be tailored to individuals. Continuous glucose monitoring systems (CGMS) are a relatively new technology that have been shown to be useful in diagnosing CFRD, but the impact of CGM on the monitoring and subsequent management of CFRD remains undetermined. This application of CGM has previously been approved in people with other forms of diabetes. Method For this work, engagement with stakeholders was undertaken to devise outcomes of interest that would make a meaningful impact on the lives and wellbeing of pwCFRD and those involved with their care. A protocol for an original Cochrane systematic review on the impact of CGM on pwCFRD was then created and the review itself was conducted. This included performing a comprehensive search of five major databases and assessing the eligibility of the results for inclusion in the study. A suggested framework for future research in this area was then created. Results Out of a total of 1768 studies, once duplicates were eliminated, there were found to be no completed RCT studies that appropriately fitted the protocol’s criteria for inclusion in the review. The only study that did meet the criteria was a single RCT protocol registered at clinicaltrials.gov (NCT03939065) which had not yet been undertaken, and thus, presented no data to be analysed for the review at this time. However, once this trial is completed, it may be eligible for inclusion in an update of this review. Discussion There is currently no evidence to support the costly implementation of CGM to manage CFRD, although there are indications that CGMS are already being used in this context. CFRD is becoming more prevalent because of a range of factors including the improved life expectancy of pwCF. The impact of CFRD on peoples’ lives is of ever-growing importance and so it is now more pressing than ever to conduct research into ways to help alleviate both the treatment and disease burden for pwCFRD. Ensuring new technologies are properly evaluated will contribute to the provision of a growing and robust body of evidence which in turn will support the decision-making of policy makers, clinicians, and patients alike. As discussed, there is currently no data available on the impact of CGM on the management of pwCFRD. However, it is noted that the absence of evidence is not evidence of absence of effect. It is hoped that publication of this review will raise the profile of the question at hand and generate sufficient research to provide a route map to find the answers.