Dipeptidyl peptidase-1 inhibition in patients hospitalised with COVID-19: a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial

Background Neutrophil serine proteases are involved in the pathogenesis of COVID-19 and increased serine protease activity has been reported in severe and fatal infection. We investigated whether brensocatib, an inhibitor of dipeptidyl peptidase-1 (DPP-1; an enzyme responsible for the activation of neutrophil serine proteases), would improve outcomes in patients hospitalised with COVID-19. Methods In a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial, across 14 hospitals in the UK, patients aged 16 years and older who were hospitalised with COVID-19 and had at least one risk factor for severe disease were randomly assigned 1:1, within 96 h of hospital admission, to once-daily brensocatib 25 mg or placebo orally for 28 days. Patients were randomly assigned via a central web-based randomisation system (TruST). Randomisation was stratified by site and age (65 years or ≥65 years), and within each stratum, blocks were of random sizes of two, four, or six patients. Participants in both groups continued to receive other therapies required to manage their condition. Participants, study staff, and investigators were masked to the study assignment. The primary outcome was the 7-point WHO ordinal scale for clinical status at day 29 after random assignment. The intention-to-treat population included all patients who were randomly assigned and met the enrolment criteria. The safety population included all participants who received at least one dose of study medication. This study was registered with the ISRCTN registry, ISRCTN30564012. Findings Between June 5, 2020, and Jan 25, 2021, 406 patients were randomly assigned to brensocatib or placebo; 192 (47·3%) to the brensocatib group and 214 (52·7%) to the placebo group. Two participants were excluded after being randomly assigned in the brensocatib group (214 patients included in the placebo group and 190 included in the brensocatib group in the intention-to-treat population). Primary outcome data was unavailable for six patients (three in the brensocatib group and three in the placebo group). Patients in the brensocatib group had worse clinical status at day 29 after being randomly assigned than those in the placebo group (adjusted odds ratio 0·72 [95% CI 0·57–0·92]). Prespecified subgroup analyses of the primary outcome supported the primary results. 185 participants reported at least one adverse event; 99 (46%) in the placebo group and 86 (45%) in the brensocatib group. The most common adverse events were gastrointestinal disorders and infections. One death in the placebo group was judged as possibly related to study drug. Interpretation Brensocatib treatment did not improve clinical status at day 29 in patients hospitalised with COVID-19

Visualizing the Voiceless and Seeing the Unspeakable: Understanding International Wordless Picturebooks about Refugees

This article investigates the formal and ethical implications of the wordless picturebook about refugees, a recent and international phenomenon. Picturebooks in this small and expanding sub-genre, we argue, are part of the “children’s literature of atrocity” (Baer 382) and use the quintessential features of the wordless form to empower or disempower, humanize or otherize, their child refugee subjects. Some of the examples we engage with problematically rely upon a clumsy refugee/non-refugee binary between safe white child and seemingly perpetually unsafe black “other,” whereas the remaining examples use the wordless form to create more collaborative, dialogical, and less binarized depictions of the relationship between the shores of Europe and the conceptualized Global South. To represent this “unspeakable” reality through wordless picturebooks emphasizes their potency at enabling readers to take risks in their navigation of meaning, transforming non-verbal affective response into speaking the unspeakable aloud.This project has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement No. 77004

Visualizing the Voiceless and Seeing the Unspeakable: Understanding International Wordless Picturebooks about Refugees

This article investigates the formal and ethical implications of the wordless picturebook about refugees, a recent and international phenomenon. Picturebooks in this small and expanding sub-genre, we argue, are part of the “children’s literature of atrocity” (Baer 382) and use the quintessential features of the wordless form to empower or disempower, humanize or otherize, their child refugee subjects. Some of the examples we engage with problematically rely upon a clumsy refugee/non-refugee binary between safe white child and seemingly perpetually unsafe black “other,” whereas the remaining examples use the wordless form to create more collaborative, dialogical, and less binarized depictions of the relationship between the shores of Europe and the conceptualized Global South. To represent this “unspeakable” reality through wordless picturebooks emphasizes their potency at enabling readers to take risks in their navigation of meaning, transforming non-verbal affective response into speaking the unspeakable aloud.   DOI: 10.1353/jeu.2019.002

A Student Experience of Peer Assisted Study Sessions in Physiotherapy

Peer Assisted Study Sessions (PASS) were introduced as an optional learning experience in a Bachelor of Physiotherapy programme. The aim of this study was to evaluate the use of PASS from the student perspective. Eight third year physiotherapy students who had participated in PASS during their second year of training attended a focus group, at which they provided their perspectives of these PASS sessions. A transciption of the focus group outcomes was analysed qualitatively using the general inductive approach, by two independent reviewers. Overall, the students’ perceptions of PASS were positive for their learning, showing that PASS is a useful and effective adjunct to formal teaching for this group of students. Three main themes were identified: learning environment, revision and mastery of skills and clinical application. This study suggests that PASS could play a useful role in an undergraduate physiotherapy programme