Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

Curriculum change: the introduction of a thinking skills course into an upper secondary school

The thesis commences by considering the changes in the concept of intelligence over the last thirty years and the rise of programmes such as those of Lipman, de Bono, Sternberg and Feuerstein that make claims of improving the intellectual skills of school students. The Somerset Thinking Skills Course (STSC) is an example of such a programme based on Feuerstein's theory. The author seeks to evaluate the course to establish if it is a practical and effective medium for students across the full ability range of an upper school. The research takes as its core a traditional experimental quantitative paradigm, but with an additional action research methodology enabling qualitative questions to be answered by students self-reporting during and imediately after the course, and again approximately twelve moths later. A review format and structured staff interviews provide additional inputs. The qualitative methods are set within the evaluative report framework of Stufflebeam's (CIPP) model. The pilot study and the changes in the full study as it was carried out within a modular framework with different groups thus enabling an action reflection spiral is described. For a sample of 322 pupils aged 13+ allocated to four ability bands and to either a control or experimental group, three hypotheses are developed: (i) that exposure to the first module of the STSC will have the effect of increasing the scores of non-verbal IQ tests administered before and after the intervention; (ii) that there will be positive qualitative reports to suggest that the STSC is helpful in developing a heuristic approach to problem solving and learning as reported by pupils; (iii) and that the effects are sufficiently robust for the change to happen within the milieu of an upper secondary school given the common major constraints on time and resources, with staff of different academic backgrounds, lacking experience and detailed training in this general area The hypotheses are sll substantiated by the research described. The results show that the STSC is of diffential benefit to groups in lower ability bands, whereas pupils in the higher ability bands reported that they had already developed the metacognitive skills of clear mental label, analysing and synthesising, following instructions, comparing and considering alternative possibilities. There were differences, by gender, to specific parts of the course. The conclusions lead to critical consideration of improving the results by a more longitudinal approach and the difficulties of measuring changes in learning of a large number of students organised traditionally

Open PHACTS Explorer Bringing the web to the semantic web

Abstract. The Open PHACTS Explorer is a web application that supports drug discovery via the Open PHACTS API without requiring knowledge of SPARQL or the RDF data being searched. It provides a UI layer on top of the Open PHACTS linked data cache and also provides a javascript library to facilitate easy access to the Open PHACTS API. 1.