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

Perceptions of arthritis glove wear of patients with rheumatoid arthritis and persistent hand pain: A nested questionnaire study within the A‐Gloves trial

Introduction: Arthritis gloves are prescribed in rheumatoid arthritis (RA) to reduce hand pain, stiffness, and improve hand function. As part of a randomised controlled trial, this study investigated participants' perceptions of wearing arthritis gloves. Method: Participants with RA and persistent hand pain (n = 206) were randomly assigned and prescribed either loose-fitting gloves (control) or arthritis gloves (intervention), for day and/or night wear (as per individual need). At 12-weeks, the trial follow-up questionnaire also included items about whether the gloves prescribed were: beneficial or not; if yes, the benefits experienced; any problems encountered; if they stopped wearing gloves day and/or night, and why. Results: The questionnaire response rate was 154/206 (75%). In both groups, 73% reported gloves were beneficial (p = 0.97). There were no differences in types of benefits reported. The most common were: warmth (59% control: 54% intervention; p = 0.53); and comfort (54%: 62%; p = 0.29). Fewer reported problems with glove wear in the control group (33%), compared to the intervention group (49%); p = 0.05. In both groups, the most common daytime problem was inability to wear gloves for wet or dirty activities; and at night, gloves being too hot. Similar numbers in the control and intervention groups stopped wearing gloves either day or night (23%: 31%; p = 0.26), primarily for these reasons. Discussion: Participants' perceptions about wearing arthritis or loose-fitting gloves were very similar. Wearing ordinary gloves could result in similar perceived benefits to arthritis gloves.</p

A User-friendly Body Armor For Female

Den svenska polisen har många problem med deras skyddsvästar. Rikspolisstyrelsen har även märkt att det särskilt är skyddsvästen för kvinnor som de har mest problem med. Utifrån intervjuer med kvinnliga poliser i Stockholm har det kommit fram vilka de olika problemen med skyddsvästen är. Alla tyckte att det blir alldeles för varmt med västen på, särskilt på sommaren. Materialet andas intetillräckligt bra. Många känner även smärtor i både rygg och axlar. Den är för kort så den skär in i magen. Den blir framtung av extraplattan på framsidan. Ett annat problem många pratade om var att skyddsvästen sitter åt så tight så det blir svårt att andas djupa andetag om de behöver göra ansträngande uppgifter så som att springa efter någon. På grund av detta och att den dessutom blir så varm gör att många knäpper upp västen i sidan för att få in mer luft och kunna vidga bröstkorgen. Syftet med projektet är att besvara de två frågor, primär och sekundär, som ställts av FOI: 1.Hur skulle skyddsvästar vara konstruerade och utformade om de vore designade för kvinnlig personal? 2.Finns det anledning att ifrågasätta dagens standardiserade skadekriterier om bärarens kroppsvikt minskar avsevärt? Projektet har varit en iterativ process och många metoder har använts. Intervjuer och workshop har gjorts med användarna för att ha deras behov i fokus. Brainstorming och prototyper har gjorts för att enkelt kunna visa och förstå funktionerna av västarna. En kombinationsbrainstorming gjordes för att seom de olika koncepten kunde kombineras och därmed bli ännu bättre. Därefter har ett konceptval gjorts med hjälp av konceptutvärderingsmetoder så som QFD och en Pugh matris där användarnas krav har stått som grund.Det koncept som var mest omtyckt av användarna och även fick best betyg i utvärderingarna var det som var mest flexibelt. Det koncept som tillåter användarna att kunna ta djupa andetag när de utövar fysisk aktivitet. Den väst där användarna slipper knäppa upp i sidan för att låta bröstkorgen utvidgas.Västen har bättre skydd i sidan så även om skyddsvästen skulle knäppas upp kommer den ändå skydda polisen mot eventuella projektiler.Olika material för skyddsvästens yttre hölje har undersökts. Ett material som andas bra och leder bortfukt bra är det som sökts. Det material som valdes är ett naturligt funktionsmaterial som kan absorbera fukt upp till 30 % av sin vikt och på så sätt hållakroppen torr.Svaret på den andra frågeställningen har diskuterats fram. Tidigare forskning har inte dragit några slutsatser om bärarens vikt bidrar till ökad eller minskad skada från en projektil. Därför har en diskussion utifrån tidigare forskning gjorts och slutsatser har dragits mellan dem. Slutsatsen är att;Ja, det finns anledning att ifrågasätta skadekriterierna om bärarens vikt minskar avsevärt.En slutsats som dragits är att det behövs en mer nära relation mellan utveckling av dagens västar och användaren.The Swedish police have many problems with their body armor. The National Police have noticed that it particularly is the body armor made for women that they have the most problems with. Based on interviews with female police officers in Stockholm, it has emerged what the various problems with the armor is. Every one of the interviewees thought that it is far too warm with the body armor on, especially in summer. The material does not breathe well enough. Many of them also feel pain in the back and shoulders. It's too short so it chafes into the stomach. It becomes front heavy with extra plate in the front. Another problem many of them talked about was that the body armor is too tight so it becomes difficult to take deep breaths if they would have to do exhausting tasks such as running after someone. Because of this, and that it also gets so warm makes many of them unbuttoning the vest in the sides to ventilate and be able to expand the chest.The project aim is to answer the two questions, primary and secondary, that is compiled by FOI: 1. How would body armor be designed if they were made for female staff? 2. Is there a reason to question today’s standardized injury criterias if the users body weight is significantly reduced? The project has been an iterative process, and many methods have been used. Interviews and workshops have been made with the users to have their needs in focus. Brainstorming and prototyping has been made to easily view and understand the features of the vests. A combination brainstorming was done to see if the different concepts could be combined and thereby become even better. After that a concept selection was made using concept evaluation methods such as QFD and a Pugh matrix where the user requirements have been the foundation.The concept that was most liked by the users and also got best rating in the evaluations was the one that is the most flexible. It is the concept that allows the users to take deep breaths when exercising physical activity. It is the vest where the users do not have to unbutton in the side to let the chest expand. The vest also has better protection in side so even if the armor would be unbuttoned, it will still protect the police against projectiles.Various materials for the body armors outer casing have been investigated. A material that has a high breathability and can lead the moisture away is the material that has been sought. The chosen material is a natural functional material that can absorb moisture up to 30% of its weight and therefore is keeping the body dry.The answer to the secondary question has been discussed. Previous research has not drawn any conclusions about if the wearer's weight contributes to an increased or decreased injury from a projectile. Therefore, a discussion based on previous research done and conclusions have been drawn between them. The conclusion is that; Yes, there are reasons to doubt the injury criteria if the wearer's weight is significantly reduced.A conclusion drawn is that a closer relationship between the development of today's vests and user is needed

Probing the circumstellar structures of T Tauri stars and their relationship to those of Herbig stars

Peer reviewe

The effects of arthritis gloves on people with Rheumatoid Arthritis or Inflammatory Arthritis with hand pain: a study protocol for a multi-centre randomised controlled trial (the A-GLOVES trial)

Abstract Background Arthritis gloves are regularly provided as part of the management of people with rheumatoid arthritis (RA) and undifferentiated (early) inflammatory arthritis (IA). Usually made of nylon and elastane (i.e. Lycra®), these arthritis gloves apply pressure with the aims of relieving hand pain, stiffness and improving hand function. However, a systematic review identified little evidence supporting their use. We therefore designed a trial to compare the effectiveness of the commonest type of arthritis glove provided in the United Kingdom (Isotoner gloves) (intervention) with placebo (control) gloves (i.e. larger arthritis gloves providing similar warmth to the intervention gloves but minimal pressure only) in people with these conditions. Methods Participants aged 18 years and over with RA or IA and persistent hand pain will be recruited from National Health Service Trusts in the United Kingdom. Following consent, participants will complete a questionnaire booklet, then be randomly allocated to receive intervention or placebo arthritis gloves. Within three weeks, they will be fitted with the allocated gloves by clinical specialist rheumatology occupational therapists. Twelve weeks (i.e. the primary endpoint) after completing the baseline questionnaire, participants will complete a second questionnaire, including the same measures plus additional questions to explore adherence, benefits and problems with glove-wear. A sub-sample of participants from each group will be interviewed at the end of their participation to explore their views of the gloves received. The clinical effectiveness and cost-effectiveness of the intervention, compared to placebo gloves, will be evaluated over 12 weeks. The primary outcome measure is hand pain during activity. Qualitative interviews will be thematically analysed. Discussion This study will evaluate the commonest type of arthritis glove (Isotoner) provided in the NHS (i.e. the intervention) compared to a placebo glove. The results will help occupational therapists, occupational therapy services and people with arthritis make informed choices as to the value of arthritis gloves. If effective, arthritis gloves should become more widely available in the NHS to help people with RA and IA manage hand symptoms and improve performance of daily activities, work and leisure. If not, services can determine whether to cease supplying these to reduce service costs. Trial registration ISRCTN Registry: ISRCTN25892131 Registered 05/09/201

Odanacatib for the treatment of postmenopausal osteoporosis : Results of the LOFT multicentre, randomised, double-blind, placebo-controlled trial and LOFT Extension study

Background Odanacatib, a cathepsin K inhibitor, reduces bone resorption while maintaining bone formation. Previous work has shown that odanacatib increases bone mineral density in postmenopausal women with low bone mass. We aimed to investigate the efficacy and safety of odanacatib to reduce fracture risk in postmenopausal women with osteoporosis. Methods The Long-term Odanacatib Fracture Trial (LOFT) was a multicentre, randomised, double-blind, placebo-controlled, event-driven study at 388 outpatient clinics in 40 countries. Eligible participants were women aged at least 65 years who were postmenopausal for 5 years or more, with a femoral neck or total hip bone mineral density T-score between −2·5 and −4·0 if no previous radiographic vertebral fracture, or between −1·5 and −4·0 with a previous vertebral fracture. Women with a previous hip fracture, more than one vertebral fracture, or a T-score of less than −4·0 at the total hip or femoral neck were not eligible unless they were unable or unwilling to use approved osteoporosis treatment. Participants were randomly assigned (1:1) to either oral odanacatib (50 mg once per week) or matching placebo. Randomisation was done using an interactive voice recognition system after stratification for previous radiographic vertebral fracture, and treatment was masked to study participants, investigators and their staff, and sponsor personnel. If the study completed before 5 years of double-blind treatment, consenting participants could enrol in a double-blind extension study (LOFT Extension), continuing their original treatment assignment for up to 5 years from randomisation. Primary endpoints were incidence of vertebral fractures as assessed using radiographs collected at baseline, 6 and 12 months, yearly, and at final study visit in participants for whom evaluable radiograph images were available at baseline and at least one other timepoint, and hip and non-vertebral fractures adjudicated as being a result of osteoporosis as assessed by clinical history and radiograph. Safety was assessed in participants who received at least one dose of study drug. The adjudicated cardiovascular safety endpoints were a composite of cardiovascular death, myocardial infarction, or stroke, and new-onset atrial fibrillation or flutter. Individual cardiovascular endpoints and death were also assessed. LOFT and LOFT Extension are registered with ClinicalTrials.gov (number NCT00529373) and the European Clinical Trials Database (EudraCT number 2007-002693-66). Findings Between Sept 14, 2007, and Nov 17, 2009, we randomly assigned 16 071 evaluable patients to treatment: 8043 to odanacatib and 8028 to placebo. After a median follow-up of 36·5 months (IQR 34·43–40·15) 4297 women assigned to odanacatib and 3960 assigned to placebo enrolled in LOFT Extension (total median follow-up 47·6 months, IQR 35·45–60·06). In LOFT, cumulative incidence of primary outcomes for odanacatib versus placebo were: radiographic vertebral fractures 3·7% (251/6770) versus 7·8% (542/6910), hazard ratio (HR) 0·46, 95% CI 0·40–0·53; hip fractures 0·8% (65/8043) versus 1·6% (125/8028), 0·53, 0·39–0·71; non-vertebral fractures 5·1% (412/8043) versus 6·7% (541/8028), 0·77, 0·68–0·87; all p<0·0001. Combined results from LOFT plus LOFT Extension for cumulative incidence of primary outcomes for odanacatib versus placebo were: radiographic vertebral fractures 4·9% (341/6909) versus 9·6% (675/7011), HR 0·48, 95% CI 0·42–0·55; hip fractures 1·1% (86/8043) versus 2·0% (162/8028), 0·52, 0·40–0·67; non-vertebral fractures 6·4% (512/8043) versus 8·4% (675/8028), 0·74, 0·66–0·83; all p<0·0001. In LOFT, the composite cardiovascular endpoint of cardiovascular death, myocardial infarction, or stroke occurred in 273 (3·4%) of 8043 patients in the odanacatib group versus 245 (3·1%) of 8028 in the placebo group (HR 1·12, 95% CI 0·95–1·34; p=0·18). New-onset atrial fibrillation or flutter occurred in 112 (1·4%) of 8043 patients in the odanacatib group versus 96 (1·2%) of 8028 in the placebo group (HR 1·18, 0·90–1·55; p=0·24). Odanacatib was associated with an increased risk of stroke (1·7% [136/8043] vs 1·3% [104/8028], HR 1·32, 1·02–1·70; p=0·034), but not myocardial infarction (0·7% [60/8043] vs 0·9% [74/8028], HR 0·82, 0·58–1·15; p=0·26). The HR for all-cause mortality was 1·13 (5·0% [401/8043] vs 4·4% [356/8028], 0·98–1·30; p=0·10). When data from LOFT Extension were included, the composite of cardiovascular death, myocardial infarction, or stroke occurred in significantly more patients in the odanacatib group than in the placebo group (401 [5·0%] of 8043 vs 343 [4·3%] of 8028, HR 1·17, 1·02–1·36; p=0·029, as did stroke (2·3% [187/8043] vs 1·7% [137/8028], HR 1·37, 1·10–1·71; p=0·0051). Interpretation Odanacatib reduced the risk of fracture, but was associated with an increased risk of cardiovascular events, specifically stroke, in postmenopausal women with osteoporosis. Based on the overall balance between benefit and risk, the study's sponsor decided that they would no longer pursue development of odanacatib for treatment of osteoporosis