The effects of inhaled corticosteroids on healthy airways

Background: The effects of inhaled corticosteroids (ICS) on healthy airways are poorly defined. Objectives: To delineate the effects of ICS on gene expression in healthy airways, without confounding caused by changes in disease-related genes and disease-related alterations in ICS-responsiveness. Methods: Randomised open-label bronchoscopy study of high dose ICS therapy in 30 healthy adult volunteers randomised 2:1 to i) fluticasone propionate 500 mcg bd daily or, ii) no treatment, for 4 weeks. Laboratory staff were blinded to allocation. Biopsies and brushings were analysed by immunohistochemistry, bulk RNA sequencing, DNA methylation array and metagenomics. Results: ICS induced small between-group differences in blood and lamina propria eosinophil numbers, but not in other immunopathological features, blood neutrophils, FeNO, FEV1, microbiome or DNA methylation. ICS treatment upregulated 72 genes in brushings and 53 genes in biopsies, and downregulated 82 genes in brushings and 416 genes in biopsies. The most downregulated genes in both tissues were canonical markers of type-2 inflammation (FCER1A, CPA3, IL33, CLEC10A, SERPINB10 and CCR5), T cell-mediated adaptive immunity (TARP, TRBC1, TRBC2, PTPN22, TRAC, CD2, CD8A, HLA-DQB2, CD96, PTPN7), B cell immunity (CD20, immunoglobulin heavy and light chains), and innate immunity, including CD48, Hobit, RANTES, Langerin and GFI1. An IL-17-dependent gene signature was not upregulated by ICS. Conclusions: In healthy airways, 4-week ICS exposure reduces gene expression related to both innate and adaptive immunity, and reduces markers of type-2 inflammation. This implies that homeostasis in health involves tonic type-2 signalling in the airway mucosa, which is exquisitely sensitive to ICS. Registered at ClincialTrials.gov: NCT0247682

Quality and Reporting of Diagnostic Accuracy Studies in TB, HIV and Malaria: Evaluation Using QUADAS and STARD Standards

BackgroundPoor methodological quality and reporting are known concerns with diagnostic accuracy studies. In 2003, the QUADAS tool and the STARD standards were published for evaluating the quality and improving the reporting of diagnostic studies, respectively. However, it is unclear whether these tools have been applied to diagnostic studies of infectious diseases. We performed a systematic review on the methodological and reporting quality of diagnostic studies in TB, malaria and HIV.MethodsWe identified diagnostic accuracy studies of commercial tests for TB, malaria and HIV through a systematic search of the literature using PubMed and EMBASE (2004–2006). Original studies that reported sensitivity and specificity data were included. Two reviewers independently extracted data on study characteristics and diagnostic accuracy, and used QUADAS and STARD to evaluate the quality of methods and reporting, respectively.FindingsNinety (38%) of 238 articles met inclusion criteria. All studies had design deficiencies. Study quality indicators that were met in less than 25% of the studies included adequate description of[...] and description of the team executing the test and management of indeterminate/outlier results (both 17%). The use of STARD was not explicitly mentioned in any study. Only 22% of 46 journals that published the studies included in this review required authors to use STARD

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries