RHINITIS IN THE FIRST 18 MONTHS OF LIFE: EPIDEMIOLOGY AND RELATIONSHIP WITH CO-MORBIDITIES AND RESPIRATORY VIRUSES

Ph.DDOCTOR OF PHILOSOPH

Physiological predictors of peak inspiRatory flow using Observed lung function results (POROS) : evaluation at discharge among patients hospitalized for a COPD exacerbation

This study was supported by AstraZeneca. The abstract of this paper was presented at the American Thoracic Society International Conference 2017 as a poster presentation with interim findings.Peer reviewedPublisher PD

Characteristics of patients in platform C19, a COVID-19 research database combining primary care electronic health record and patient reported information

Background Data to better understand and manage the COVID-19 pandemic is urgently needed. However, there are gaps in information stored within even the best routinely-collected electronic health records (EHR) including test results, remote consultations for suspected COVID-19, shielding, physical activity, mental health, and undiagnosed or untested COVID-19 patients. Observational and Pragmatic Research Institute (OPRI) Singapore and Optimum Patient Care (OPC) UK established Platform C19, a research database combining EHR data and bespoke patient questionnaire. We describe the demographics, clinical characteristics, patient behavior, and impact of the COVID-19 pandemic using data within Platform C19. Methods EHR data from Platform C19 were extracted from 14 practices across UK participating in the OPC COVID-19 Quality Improvement program on a continuous, monthly basis. Starting 7th August 2020, consenting patients aged 18–85 years were invited in waves to fill an online questionnaire. Descriptive statistics were summarized using all data available up to 22nd January 2021. Findings From 129,978 invitees, 31,033 responded. Respondents were predominantly female (59.6%), white (93.5%), and current or ex-smokers (52.6%). Testing for COVID-19 was received by 23.8% of respondents, of which 7.9% received positive results. COVID-19 symptoms lasted ≥4 weeks in 19.5% of COVID-19 positive respondents. Up to 39% respondents reported a negative impact on questions regarding their mental health. Most (67%-76%) respondents with asthma, Chronic Obstructive Pulmonary Disease (COPD), diabetes, heart, or kidney disease reported no change in the condition of their diseases. Interpretation Platform C19 will enable research on key questions relating to COVID-19 pandemic not possible using EHR data alone

Discovery and characterization of novel cyclotides originated from chimeric precursors consisting of Albumin-1 chain a and cyclotide domains in the Fabaceae family

The tropical plant Clitoria ternatea is a member of the Fabaceae family well known for its medicinal values. Heat extraction of C. ternatea revealed that the bioactive fractions contained heat-stable cysteine-rich peptides (CRPs). The CRP family of A1b (Albumin-1 chain b/leginsulins), which is a linear cystine knot CRP, has been shown to present abundantly in the Fabaceae. In contrast, the cyclotide family, which also belongs to the cystine knot CRPs but with a cyclic structure, is commonly found in the Rubiaceae, Violaceae, and Cucurbitaceae families. In this study, we report the discovery of a panel of 15 heat-stable CRPs, of which 12 sequences (cliotide T1-T12) are novel. We show unambiguously that the cliotides are cyclotides and not A1bs, as determined by their sequence homology, disulfide connectivity, and membrane active properties indicated by their antimicrobial activities against Escherichia coli and cytotoxicities to HeLa cells. We also show that cliotides are prevalent in C. ternatea and are found in every plant tissue examined, including flowers, seeds, and nodules. In addition, we demonstrate that their precursors are chimeras, half from cyclotide and the other half from Albumin-1, with the cyclotide domain displacing the A1b domain in the precursor. Their chimeric structures likely originate from either horizontal gene transfer or convergent evolution in plant nuclear genomes, which are exceedingly rare events. Such atypical genetic arrangement also implies a different mechanism of biosynthetic processing of cyclotides in the Fabaceae and provides new understanding of their evolution in plants.Accepted versio

CONQUEST : a quality improvement program for defining and optimizing standards of care for modifiable high-risk COPD patients

Funding This study was conducted by Optimum Patient Care Global and the Observational and Pragmatic Research Institute (OPRI) Pte Ltd and was co-funded by Optimum Patient Care Global and AstraZeneca. No funding was received by the Observational & Pragmatic Research Institute Pte Ltd (OPRI) for its contribution. Acknowledgements Hana Muellerova, Patrick Darken, Paul Dorinsky, Frank Trudo, and Alex De Giorgio-Miller of AstraZeneca are acknowledged for their contribution to protocol development. Writing, editorial support, and/or formatting assistance in the development of this manuscript was provided by Shilpa Suresh, MSc, of the Observational and Pragmatic Research Institute, Singapore. Professor Dave Singh is supported by the National Institute for Health Research (NIHR) Manchester Biomedical Research Centre (BRC).Peer reviewedPublisher PD

A Comparison of the Real-Life Clinical Effectiveness of the Leading Licensed ICS/LABA Combination Inhalers in the Treatment for COPD

Introduction: The Fostair® 100/6 (BDP/FF) pressurized metered-dose inhaler, delivering an extrafine formulation, is licensed for asthma and COPD in the UK. However, its real-life effectiveness for COPD has not been evaluated. This study compared the clinical effectiveness of BDP/FF against other licensed ICS/LABA combination inhalers: the Seretide® Accuhaler® (FP/SAL) and the Symbicort® Turbohaler® (BUD/FF). Methods: A matched historical cohort study was conducted using records of patients with diagnostic codes for COPD from the Optimum Patient Care Research Database (OPCRD). Patients who had received BDP/FF as their first ICS/LABA were matched 1:1 with patients who had received FP/SAL or BUD/FF, resulting in two matched comparisons. Additional analysis was conducted on patients who had never had diagnostic codes for asthma. Noninferiority in terms of the proportion of patients with moderate/severe COPD exacerbations on the different inhalers in the following year was assessed. Noninferiority was achieved if the upper CI limit were ≤1.2. Results: This study included 537 and 540 patient pairs in the BDP/FF vs FP/SAL cohort and the BDP/FF vs BUD/FF cohort, respectively. The proportion of patients with COPD exacerbations in the BDP/FF group was not significantly different from either the FP/SAL (68.7% vs 70.2%, AOR 0.89, 95% CI 0.67-1.19) or BUD/FF group (68.5% vs 69.4%, AOR 0.79, 95% CI 0.58-1.08). Noninferiority of BDP/FF in preventing COPD exacerbations was fulfilled in both comparisons. In patients without asthma, BDP/FF was also noninferior to BUD/FF (proportion with COPD exacerbations, 67.8% vs 64.7%, AOR 0.79, 95% CI 0.51-1.1997). Additionally, a significantly lower proportion of patients prescribed BDP/FF had COPD exacerbations than FP/SAL (64.8% vs 73.7%, AOR 0.64 95% CI 0.43-0.96). Conclusion: Initiating ICS/LABA treatment of COPD with extrafine-formulation BDP/FF was noninferior in preventing moderate/severe exacerbations compared to FP/SAL and BUD/FF.This article is available to RD&E staff via NHS OpenAthens. Click on the Publisher URL, and log in with NHS OpenAthens if prompted.This study was funded by Chiesi Limited. The sponsor is involved in the design and presentation of the study.published version, accepted versio

Maternal PUFA status and offspring allergic diseases up to the age of 18 months

10.1017/S000711451500001XBritish Journal of Nutrition1136975-983GUSTO (Growing up towards Healthy Outcomes