SummaryBackgroundStaphylococcus 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.MethodsIn 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.FindingsBetween 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).InterpretationAdjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia.FundingUK National Institute for Health Research Health Technology Assessment.

Low-dose MTX administered weekly remains a mainstay in the therapy of RA. There is a belief amongst rheumatologists that RA patients taking MTX have both an increased risk and severity of infection. Here we review the published data on the risks of infection associated with the use of MTX in patients with RA and make some recommendations for managing MTX in patients with infection.

Abstractobjectives This study evaluates the diagnostic accuracy of Haemoglobin Colour Scale (HCS), compared with clinical diagnosis, to detect anaemia and severe anaemia in preschool-age children attending primary healthcare clinics in rural Zanzibar.methods In all participants, haemoglobin (Hb) concentration was independently estimated by clinical examination for palmar pallor, HCS and HemoCueÔ. HemoCue was considered the reference method. Data collection was integrated into the usual health services and performed by local healthcare workers (HCWs). Sensitivity, specificity, positive and negative predictive values were calculated for HCS and clinical examination for palmar pallor. The limits of agreement between HCS and HemoCue, and interobserver variability for HCS, were also defined.results A total of 799 children age 2-59 months were recruited to the study. The prevalence of anaemia (Hb < 11 g ⁄ dl) and severe anaemia (<5 g ⁄ dl) were 71% and 0.8% respectively. The sensitivity of HCS to detect anaemia was 33% [95% confidence interval (CI) 29-36] and specificity was 87% (83-91). The sensitivity of HCS to detect severe anaemia was 14% (95% CI 0-58) and specificity was 100% (99-100). The sensitivity of palmar pallor to detect anaemia was low, but superior to HCS (58% vs. 33%, P < 0.001); specificity was inferior to HCS (55% vs. 87%, P < 0.001). There was no evidence of a difference in either sensitivity (P > 0.1) or specificity (P > 0.1) between HCS and palmar pallor to detect severe anaemia.conclusions Haemoglobin Colour Scale does not improve the capacity of HCWs to diagnose anaemia in this population. Accuracy is limited by considerable variability in the performances of test operators. However, optimizing the training protocol for those using the test may improve performance.

Influenza B virus infections were documented in Houston, Texas, in 726 patients with febrile respiratory illnesses who presented to representative primary care facilities during the 1976-1977 respiratory disease season. This epidemic followed a "herald wave" of illness associated with influenza B during the preceding spring. Over one-half the virus isolates were from children aged 5-19 years, and school absenteeism rates indicated that about 40 per cent of the students in the Houston area were ill enough to miss school during the epidemic. The rapid rise in the number of cases among students after the school holiday recess demonstrated the importance of school attendance for the rapid dissemination of influenza viruses. During the later phase of the epidemic, most of the cases were preschool children and adults. In addition to disease of the respiratory tract, the epidemic was accompanied by cases of Reye's syndrome at a rate expected for an urban area.