FLASH GLUCOSE MONITORING WITH THE FREESTYLE LIBRE 2: RESULTS FROM THE FLASH-UK RANDOMISED CONTROLLED TRIAL (ON BEHALF OF THE STUDY GROUP)

Objectives To evaluate whether intermittently scanned continuous glucose monitoring (isCGM) with optional alarms (FreeStyle Libre 2) improves glycaemia as measured by HbA1c and sensor-based gluco-metrics, patient reported outcome measures (PROMS) and cost-effectiveness compared with selfmonitoring of blood glucose (SMBG). Design Flash UK is a multicenter, open-label, two arm, parallel, randomised controlled trial delivered in 7 specialist hospital diabetes clinics and 1 primary care centre. Participants 156 people with Type 1 diabetes, age 16 years and over treated with either multiple daily insulin injections or insulin pump therapy with HbA1c 7.5%-11% were randomised. Interventions Participants were randomised (1:1) to the FreeStyle Libre 2 (n = 72) or standard care with SMBG (n = 69). Participants were reviewed at 4, 12 and 24 weeks post-randomisation. Education and treatment optimisation was provided to both groups at randomisation, 4 and 12 weeks. Participants in the SMBG arm wore blinded glucose sensor (Freestyle Libre Pro) during the last 2 weeks of the study;all participants wore a 2-week blinded sensor prior to randomisation. All study visits were conducted either inperson or virtually owing to the COVID-19 pandemic. Main outcome measures The primary outcome was HbA1c at 24 weeks, analysed by intention to treat. Secondary outcomes included glucose time in range (3.9 to 10mmol/l), time below and above range and glucose variability. PROMS included EQ-5DL-5L, Type 1 Diabetes Distress Scale, Diabetes fear of injecting and self-testing, Diabetes Eating Problem Survey, Diabetes Treatment Satisfaction, Patient Health Questionnaire and The Glucose Monitoring Satisfaction Survey. Economic evaluation included healthcare resource use, insulin usage and Freestyle Libre 2 utilisation. Results & Conclusion Results and conclusions will be presented during the 15th International Conference on Advanced Technologies & Treatments for Diabetes, April 27 to 30th Barcelona, Spain and Online.

Parenchymal involvement on CT pulmonary angiography in SARS-CoV-2 Alpha variant infection and correlation of COVID-19 CT severity score with clinical disease severity and short-term prognosis in a UK cohort.

AIM: To determine if there is a difference in radiological, biochemical, or clinical severity between patients infected with Alpha-variant SARS-CoV-2 compared with those infected with pre-existing strains, and to determine if the computed tomography (CT) severity score (CTSS) for COVID-19 pneumonitis correlates with clinical severity and can prognosticate outcomes. MATERIALS AND METHODS: Blinded CTSS scoring was applied to 137 hospital patients who had undergone both CT pulmonary angiography (CTPA) and whole-genome sequencing of SARS-CoV-2 within 14 days of CTPA between 1/12/20-5/1/21. RESULTS: There was no evidence of a difference in imaging severity on CTPA, viral load, clinical parameters of severity, or outcomes between Alpha and preceding variants. CTSS on CTPA strongly correlates with clinical and biochemical severity at the time of CTPA, and with patient outcomes. Classifying CTSS into a binary value of "high" and "low", with a cut-off score of 14, patients with a high score have a significantly increased risk of deterioration, as defined by subsequent admission to critical care or death (multivariate hazard ratio [HR] 2.76, p<0.001), and hospital length of stay (17.4 versus 7.9 days, p<0.0001). CONCLUSION: There was no evidence of a difference in radiological severity of Alpha variant infection compared with pre-existing strains. High CTSS applied to CTPA is associated with increased risk of COVID-19 severity and poorer clinical outcomes and may be of use particularly in settings where CT is not performed for diagnosis of COVID-19 but rather is used following clinical deterioration.

Transmission of SARS-COV-2 in the hospital setting: Who is infecting whom?

Introduction: A better understanding of the relative importance of different transmission pathways of SARS-CoV-2 in hospital settings has the potential to help improve targeting of control measures aimed at reducing nosocomial spread. Objectives: To quantify the associations between risks of nosocomial SARS-CoV-2 infection and exposure on the same ward to infected healthcare workers (HCWs), to patients likely to have been infected nosocomially, and to patients with community onset COVID-19. Methods: Ward-level data were collected from four teaching hospitals in Oxfordshire, UK, over an 8 month period in 2020. SARS-CoV-2 infections were identified using both PCR results from symptomatic and asymptomatic testing and serological data coupled with symptom recall. A series of statistical models were used to quantify associations between exposures and probable hospital transmission events. Results: Risk to patients of probable nosocomial acquisition was most strongly associated with exposure to other patients with hospitalacquired SARS-CoV-2 (aOR, 1.76, 95%CI 1.51, 2.04), followed by the presence of an infected HCW on the same ward (aOR 1.45, 95%CI 1.22,1.71). The association with patients with community onset COVID- 19 was weaker (aOR 1.12, 95%CI 0.96,1.26). Transmission to HCWs was associated with exposure to other infectious HCWs and patients with hospital-acquired SARS-CoV-2 (aOR 1.66, 95%CI 1.55,1.78 and aOR 1.45, 95%CI 1.32,1.58 respectively). The introduction of more stringent infection prevention and control measures which included testing all patients for SARS-CoV-2 by PCR on admission and at weekly intervals was associated with substantial reduction in transmission risk to both patients (adjusted odds ratio, aOR 0.25, 95%CI 0.14, 0.42) and HCWs (aOR 0.43, 95%CI 0.34, 0.53). Conclusion: Patients who acquired SARS-CoV-2 in the hospital and, to a lesser degree, infectious HCWs likely working prior to the onset of symptoms, were the most strongly associated with increased risk of SARSCoV- 2 transmission. In contrast, exposure to patients who had acquired SARS-CoV-2 in the community was associated with, at most, modest increases in the daily risk of infection for both healthcare staff and the other patients.

Radiotranscriptomic analysis of perivascular adipose tissue quantifies vascular inflammation in COVID-19 from routine ct angiograms: stratification of “new uk variant” infection and prediction of inhospital outcomes

Background Evidence suggests that adverse outcomes in COVID-19 may be driven by a cytokine-induced vascular inflammatory response, caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). Aim We aimed to develop a non-invasive method for quantifying cytokine-driven vascular inflammation in patients with acute COVID-19 infection that could allow risk stratification. Methods We developed a platform for rapid development of novel imaging biomarkers of vascular inflammation, by applying quantitative radiotranscriptomics to images from standard Computed Tomography Angiography (CTA). We used this platform to train a radiotranscriptomic signature (C19-RS) from the perivascular space around the aorta and the internal mammary artery, visualized in routine chest CTAs, to best describe cytokine-driven vascular inflammation, defined using transcriptomic profiles from RNA sequencing data from human arterial biopsies. This signature was tested externally in 435 clinically indicated CT pulmonary angiograms (CTPAs) from patients with or without COVID-19 from 3 different geographical regions. Results COVID-19 patients were characterised by significantly higher C19-RS values (adjusted odds ratio of 2.97 [95%CI: 1.43-6.27], p=0.004), while patients infected with the new B.1.1.7 variant (“UK variant”) were also found to have higher C19-RS values compared to those with the original variant, evidence suggestive of higher degrees of vascular inflammation. C19-RS had prognostic value for in-hospital mortality in COVID-19, with hazard ratios of 3.31 ([95%CI: 1.49-7.33], p=0.003) and 2.58 ([95%CI: 1.10-6.05], p=0.028) in two external testing cohorts respectively, after correction for clinical factors and biochemical biomarkers of inflammation (WBC, CRP) and myocardial injury (troponin). Importantly, the corrected HR for in-hospital mortality was 8.24[95%CI: 2.16- 31.36], P=0.002 for those who received no treatment with dexamethasone, but only 2.27[95%CI: 0.69-7.55], p=0.18 in those who received dexamethasone after the test, suggesting that anti-inflammatory treatment may be modifying the natural history of COVID-19 infection by improving outcomes specifically in those patients with high vascular inflammation. Conclusions Our study introduces a new radiotranscriptomic signature, C19-RS, extracted from routine CTPAs, trained to detect cytokine-driven arterial inflammation, and demonstrates that vascular inflammation determined in this way has prognostic value in patients with COVID-19. The “UK variant” leads to higher vascular inflammation measured in this way, and the risk associated with COVID-19 arteritis is modifiable by dexamethasone.

Flash glucose monitoring with the FreeStyle Libre 2 compared with self-monitoring of blood glucose in suboptimally controlled type 1 diabetes: the FLASH-UK randomised controlled trial protocol.

INTRODUCTION: Optimising glycaemic control in type 1 diabetes (T1D) remains challenging. Flash glucose monitoring with FreeStyle Libre 2 (FSL2) is a novel alternative to the current standard of care self-monitoring of blood glucose (SMBG). No randomised controlled trials to date have explored the potential benefits of FSL2 in T1D. We aim to assess the impact of FSL2 in people with suboptimal glycaemic control T1D in comparison with SMBG. METHODS: This open-label, multicentre, randomised (via stochastic minimisation), parallel design study conducted at eight UK secondary and primary care centres will aim to recruit 180 people age ≥16 years with T1D for >1 year and glycated haemoglobin (HbA1c) 7.5%-11%. Eligible participants will be randomised to 24 weeks of FSL2 (intervention) or SMBG (control) periods, after 2-week of blinded sensor wear. Participants will be assessed virtually or in-person owing to the COVID-19 pandemic. HbA1c will be measured at baseline, 12 and 24 weeks (primary outcome). Participants will be contacted at 4 and 12 weeks for glucose optimisation. Control participants will wear a blinded sensor during the last 2 weeks. Psychosocial outcomes will be measured at baseline and 24 weeks. Secondary outcomes include sensor-based metrics, insulin doses, adverse events and self-report psychosocial measures. Utility, acceptability, expectations and experience of using FSL2 will be explored. Data on health service resource utilisation will be collected. ANALYSIS: Efficacy analyses will follow intention-to-treat principle. Outcomes will be analysed using analysis of covariance, adjusted for the baseline value of the corresponding outcome, minimisation factors and other known prognostic factors. Both within-trial and life-time economic evaluations, informed by modelling from the perspective of the National Health Service setting, will be performed. ETHICS: The study was approved by Greater Manchester West Research Ethics Committee (reference 19/NW/0081). Informed consent will be sought from all participants. TRIAL REGISTRATION NUMBER: NCT03815006. PROTOCOL VERSION: 4.0 dated 29 June 2020.