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

Cost effective deformable mirror technology for astronomy applications

This thesis presents work undertaken by the author in the course of studies for an Engineering Doctorate at the School of Engineering and Physical Sciences of Heriot Watt University, and the United Kingdom Astronomy Technology Centre. The motivation for the work is to make adaptive optics more accessible to astronomy applications where cost has been a factor. At present the complexity and cost of a principal component of adaptive optic systems, the deformable mirror (DM), has limited its adoption in instrumentation and industrial applications. Novel contributions to the general body of knowledge include: a) The development of an integrated multi-layer PZT 196 actuators array on a 1.2 mm pitch. The array is constructed from 85 layers, each 20 µm thick giving an extension of 2 µm for an applied voltage of 80 Volts. b) The development of electronics for a low cost, array addressable, actuator drive which facilitates a parametric comparison of actuator permittivity to actuator extension. A 5% resolution of actuator extension was achieved with small extension loss of 62.5 picometers/second at refresh rate of up to 500 Hz. c) Reliable zeolite loaded epoxy bonding of the deformable mirror surface to the actuator array through the introduction of 1 µm groves in the side walls of the mirror support legs. Bond strength of 4.1 MPa was achieved which is greater than the 1.2 MPa required. This thesis opens the prospect of the construction of actuator staves leading to an increase the versatility of array construction. The advantages identified include reductions of the complexity of forming additional electrodes and of tolerance on actuator dicing to form individual actuators in the array. Solutions have been identified towards a future prototype deformable mirror with integrated electronic actuator drive and extension sensing

Extension sensing actuator

A device comprising a solid-state actuator (100), means for inputting an acoustic signal to the actuator (104) and means for measuring the resultant signal (104). The measured acoustic signal can be used to determine the extension of the solid-state actuator

Extension sensing actuator

A device comprising a solid-state actuator (100), means for inputting an acoustic signal to the actuator (104) and means for measuring the resultant signal (104). The measured acoustic signal can be used to determine the extension of the solid-state actuator