ABSTRACT
BACKGROUND: Cystic fibrosis (CF) is one of the most common life-shortening autosomal-recessive genetic conditions with around 100,000 people affected globally. CF mainly affects the respiratory system, but cystic fibrosis-related diabetes (CFRD) is a common extrapulmonary co-morbidity and causes excess morbidity and mortality in this population. Continuous glucose monitoring systems (CGMS) are a relatively new technology and, as yet, the impact of these on the monitoring and subsequent management of CFRD remains undetermined. OBJECTIVES: To establish the impact of insulin therapy guided by continuous glucose monitoring compared to insulin therapy guided by other forms of glucose data collection on the lives of people with CFRD. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of latest search: 23 September 2021. We also searched the reference lists of relevant articles and reviews and online trials registries. Date of last search: 23 September 2021. SELECTION CRITERIA: Randomised controlled studies comparing insulin regimens led by data from CGMS (including real-time or retrospective data, or both) with insulin regimens guided by abnormal blood glucose measurements collected through other means of glycaemic data collection in people with CFRD. Studies with a cross-over design, even with a washout period between intervention arms, are not eligible for inclusion due to the potential long-term impact of each of the interventions and the potential to compromise the outcomes of the second intervention. DATA COLLECTION AND ANALYSIS: No studies were included in the review, meaning that no data were available to be collected for analysis. MAIN RESULTS: Review authors screened 14 studies at the full-text stage against the review's inclusion criteria. Consequently, seven were excluded due to the study type being ineligible (not randomised), two studies were excluded due to their cross-over design, and two studies was excluded since the intervention used was not eligible and one was a literature review. One study in participants hospitalised for a pulmonary exacerbation is ongoing. Investigators are comparing insulin dosing via insulin pump with blood sugar monitoring by a CGMS to conventional diabetes management with daily insulin injections (or on an insulin pump if already on an insulin pump in the outpatient setting) and capillary blood glucose monitoring. The participants in the control arm will wear a blinded continuous glucose monitoring system for outcome assessment. In addition to this, one further study is still awaiting classification, and will be screened to determine whether it is eligible for inclusion, or is to be excluded, in an update of this review. AUTHORS' CONCLUSIONS: No studies were included in the review, indicating that there is currently insufficient evidence to determine the impact of insulin therapy guided by CGMS compared to insulin therapy guided by other forms of glucose data collection on the lives of people with CFRD, nor on potential adverse effects of continuous glucose monitoring in this context. Randomised controlled studies are needed to generate evidence on the efficacy and safety of continuous glucose monitoring in people with CFRD. There is one relevant ongoing study that may be eligible for inclusion in a future update of this Cochrane Review, and whose results may help answer the review question.
Subject(s)
Cystic Fibrosis , Diabetes Mellitus , Blood Glucose , Blood Glucose Self-Monitoring , Cystic Fibrosis/complications , Humans , Retrospective StudiesABSTRACT
BACKGROUND: Nephritis is a recognised complication of IgA vasculitis (IgAV, Henoch-Schönlein purpura) contributing to 1-2% of all chronic kidney disease (CKD) stage 5. Improved understanding may reduce irreversible damage in IgAV nephritis (IgAV-N). OBJECTIVE: The aim of this study was to perform a comprehensive systematic literature review to identify promising clinical and pre-clinical urine biomarkers in children with IgAV-N that could predict the presence of nephritis and/or determine its severity. METHODS: A systematic literature review was performed using four search engines and a predefined search term strategy. Promising biomarkers were divided in terms of clinical or pre-clinical and ability to predict the presence of nephritis or determine its severity. Results were described using statistical significance (p < 0.05) and area under the curve (AUC) values. RESULTS: One hundred twenty-one studies were identified; 13 were eligible. A total of 2446 paediatric patients were included: healthy controls (n = 761), children with IgAV-N (n = 1236) and children with IgAV without nephritis (IgAV-noN, n = 449). Fifty-one percent were male, median age 7.9 years. The clinical markers, 24-h protein quantity and urine protein:creatinine ratio, were deemed acceptable for assessing severity of nephritis (AUC < 0.8). Urinary albumin concentration (Malb) performed well (AUC 0.81-0.98). The most promising pre-clinical urinary biomarkers in predicting presence of nephritis were as follows: kidney injury molecule-1 (KIM-1) (AUC 0.93), monocyte chemotactic protein-1 (MCP-1) (AUC 0.83), N-acetyl-ß-glucosaminidase (NAG) (0.76-0.96), and angiotensinogen (AGT) (AUC not available). Urinary KIM-1, MCP-1, and NAG appeared to correlate with disease severity. CONCLUSIONS: Longitudinal studies are needed to assess whether pre-clinical biomarkers enhance standard of care in IgAV-N.