Anti-inflammatory therapy with nebulised dornase alfa in patients with severe COVID-19 pneumonia A Randomised Clinical Trial

BACKGROUND: SARS-CoV2 infection causes severe, life-threatening pneumonia. Hyper-inflammation, coagulopathy and lymphopenia are associated with pathology and poor outcomes in these patients. Cell-free (cf) DNA is prominent in COVID-19 patients, amplifies inflammation and promotes coagulopathy and immune dysfunction. We hypothesized that cf-DNA clearance by nebulised dornase alfa may reduce inflammation and improve disease outcomes. Here, we evaluated the efficacy of nebulized dornase alfa in patients hospitalised with severe COVID-19 pneumonia. METHODS: In this randomised controlled single-centre phase 2 proof-of-concept trial, we recruited adult patients admitted to hospital that exhibited stable oxygen saturation (≥94%) on supplementary oxygen and a C-reactive protein (CRP) level ≥30mg/L post dexamethasone treatment. Participants were randomized at a 3:1 ratio to receive twice-daily nebulised dornase alfa in addition to best available care (BAC) or BAC alone for seven days or until hospital discharge. A 2:1 ratio of historical controls to treated individuals (HC, 2:1) were included as the primary endpoint comparators. The primary outcome was a reduction in systemic inflammation measured by blood CRP levels over 7 days post-randomisation, or to discharge if sooner. Secondary and exploratory outcomes included time to discharge, time on oxygen, D-dimer levels, lymphocyte counts and levels of circulating cf-DNA. RESULTS: We screened 75 patients and enrolled 39 participants out of which 30 in dornase alfa arm, and 9 in BAC group. We also matched the recruited patients in the treated group (N=30) to historical controls in the BAC group (N=60). For the the primary outcome, 30 patients in the dornase alfa were compared to 69 patients in the BAC group. Dornase alfa treatment reduced CRP by 33% compared to the BAC group at 7-days (P=0.01). The dornase alfa group least squares mean CRP was 23.23 mg/L (95% CI 17.71 to 30.46) and the BAC group 34.82 mg/L (95% CI 28.55 to 42.47). A significant difference was also observed when only randomised participants were compared. Furthermore, compared to the BAC group, the chance of live discharge was increased by 63% in the dornase alfa group (HR 1.63, 95% CI 1.01 to 2.61, P=0.03), lymphocyte counts were improved (least-square mean: 1.08 vs 0.87, P=0.02) and markers of coagulopathy such as D-dimer were diminished (least-square mean: 570.78 vs 1656.96μg/mL, P=0.004). Moreover, the dornase alfa group exhibited lower circulating cf-DNA levels that correlated with CRP changes over the course of treatment. No differences were recorded in the rates and length of stay in the ICU or the time on oxygen between the groups. Dornase alfa was well-tolerated with no serious adverse events reported. CONCLUSION: In this proof-of-concept study in patients with severe COVID-19 pneumonia, treatment with nebulised dornase alfa resulted in a significant reduction in inflammation, markers of immune pathology and time to discharge. The effectiveness of dornase alfa in patients with acute respiratory infection and inflammation should be investigated further in larger trials

Just a wind-up? Ethnicity, religion and prejudice in Scottish football-related comedy

This article probes how media representations of football in Scotland sustain the hegemonic ideologies associated with ethnicity and religion. The paper probes the football-related comedy output of one radio programme; radio output and football comedy are both neglected cultural material in studies of sport in Scotland. It argues that ambiguity and allusive language in comedy construct multiple interpretative possibilities that can demean the social and cultural identity of particular groups in society. The discussion analyses specific sketches from the Scottish radio comedy show Watson's Wind Up. It is concluded that although humorous, these sketches reveal how ideas, myths and stereotypes that coalesce round Celtic FC and the Irish-descended and Catholic communities in Scotland reinforce and sustain anti-Irish and anti-Catholic bigotry

Television is happening: methodological considerations for capturing digital television reception

The more fragmented that engagements with the media become, the more important it is to understand changing audience practices for theories of social shaping. However, capturing the ways in which audiences respond to television is challenging when current technology makes new demands on the viewer: digital television packages offer 'interactive choices coterminous with computer interfaces. This article proposes a new methodology and demonstrates the kind of data that it makes available for studying digital television audiences. It suggests adapting the traditional metaphor of 'flow and combining an understanding of television-as-text with television-as-technology to explore the social contexts of new textual possibilities against the backdrop of claims made about 'new media. This is achieved by allowing the phenomenological aspects of television to inform an empirical study of television in sociocommunicative contexts. Locating mediated communication within everyday social interaction invites questions about what is new about the social shaping of the digital TV interface

Service industry clustering: A comparison of broadcasting in three city-regions

Drawing from two major studies of clustering in the UK broadcasting industry, this paper finds compelling differences between clusters. Differences which explain performance variation and provide strong implications for the extant literature and UK regional policy. The paper finds that (a) regional processes have been overplayed with the importance of both broader external connectivity and narrower local impacts of location underestimated; (b) the policy-makers’ conception of a successful cluster underplays the importance of large hub firms; (c) national policy has been more effective than regional policy in promoting UK broadcasting clusters; and, (d) policy-makers should not overlook traditional business support

The world according to sound: investigating the world of walkman users

Through the analysis of Walkman use I propose a reevaluation of the significance of the auditory in everyday experience. I argue that the role of sound has been largely ignored in the literature on media and everyday life resulting in systematic distortions of the meanings attached to much everyday behaviour. Sound as opposed to vision becomes the site of investigation of everyday life in this article. In focusing thus, I draw upon a range of neglected texts in order to provide a dialectical account of auditory and technologically mediated experience that avoids reductive and dichotomous categories of explanation. I propose a new evaluation of the relational nature of auditory experience whereby users manage their cognition, interpersonal behaviour and social space. The Walkman is perceived as a tool whereby users manage space, time and the boundaries around the self