Adjunctive rifampicin to reduce early mortality from Staphylococcus aureus bacteraemia: the ARREST RCT.

BACKGROUND: Staphylococcus aureus bacteraemia is a common and frequently fatal infection. Adjunctive rifampicin may enhance early S. aureus killing, sterilise infected foci and blood faster, and thereby reduce the risk of dissemination, metastatic infection and death. OBJECTIVES: To determine whether or not adjunctive rifampicin reduces bacteriological (microbiologically confirmed) failure/recurrence or death through 12 weeks from randomisation. Secondary objectives included evaluating the impact of rifampicin on all-cause mortality, clinically defined failure/recurrence or death, toxicity, resistance emergence, and duration of bacteraemia; and assessing the cost-effectiveness of rifampicin. DESIGN: Parallel-group, randomised (1 : 1), blinded, placebo-controlled multicentre trial. SETTING: UK NHS trust hospitals. PARTICIPANTS: Adult inpatients (≥ 18 years) with meticillin-resistant or susceptible S. aureus grown from one or more blood cultures, who had received < 96 hours of antibiotic therapy for the current infection, and without contraindications to rifampicin. INTERVENTIONS: Adjunctive rifampicin (600-900 mg/day, oral or intravenous) or placebo for 14 days in addition to standard antibiotic therapy. Investigators and patients were blinded to trial treatment. Follow-up was for 12 weeks (assessments at 3, 7, 10 and 14 days, weekly until discharge and final assessment at 12 weeks post randomisation). MAIN OUTCOME MEASURES: The primary outcome was all-cause bacteriological (microbiologically confirmed) failure/recurrence or death through 12 weeks from randomisation. RESULTS: Between December 2012 and October 2016, 758 eligible participants from 29 UK hospitals were randomised: 370 to rifampicin and 388 to placebo. The median age was 65 years [interquartile range (IQR) 50-76 years]. A total of 485 (64.0%) infections were community acquired and 132 (17.4%) were nosocomial; 47 (6.2%) were caused by meticillin-resistant S. aureus. A total of 301 (39.7%) participants had an initial deep infection focus. Standard antibiotics were given for a median of 29 days (IQR 18-45 days) and 619 (81.7%) participants received flucloxacillin. By 12 weeks, 62 out of 370 (16.8%) patients taking rifampicin versus 71 out of 388 (18.3%) participants taking the placebo experienced bacteriological (microbiologically confirmed) failure/recurrence or died [absolute risk difference -1.4%, 95% confidence interval (CI) -7.0% to 4.3%; hazard ratio 0.96, 95% CI 0.68 to 1.35; p = 0.81]. There were 4 (1.1%) and 5 (1.3%) bacteriological failures (p = 0.82) in the rifampicin and placebo groups, respectively. There were 3 (0.8%) versus 16 (4.1%) bacteriological recurrences (p = 0.01), and 55 (14.9%) versus 50 (12.9%) deaths without bacteriological failure/recurrence (p = 0.30) in the rifampicin and placebo groups, respectively. Over 12 weeks, there was no evidence of differences in clinically defined failure/recurrence/death (p = 0.84), all-cause mortality (p = 0.60), serious (p = 0.17) or grade 3/4 (p = 0.36) adverse events (AEs). However, 63 (17.0%) participants in the rifampicin group versus 39 (10.1%) participants in the placebo group experienced antibiotic or trial drug-modifying AEs (p = 0.004), and 24 (6.5%) participants in the rifampicin group versus 6 (1.5%) participants in the placebo group experienced drug-interactions (p = 0.0005). Evaluation of the costs and health-related quality-of-life impacts revealed that an episode of S. aureus bacteraemia costs an average of £12,197 over 12 weeks. Rifampicin was estimated to save 10% of episode costs (p = 0.14). After adjustment, the effect of rifampicin on total quality-adjusted life-years (QALYs) was positive (0.004 QALYs), but not statistically significant (standard error 0.004 QALYs). CONCLUSIONS: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S. aureus bacteraemia. FUTURE WORK: Given the substantial mortality, other antibiotic combinations or improved source management should be investigated. TRIAL REGISTRATIONS: Current Controlled Trials ISRCTN37666216, EudraCT 2012-000344-10 and Clinical Trials Authorisation 00316/0243/001. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 59. See the NIHR Journals Library website for further project information.NIHR HTA Programm

Oral versus intravenous antibiotics for bone and joint infection

BACKGROUND The management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. We investigated whether oral antibiotic therapy is noninferior to intravenous antibiotic therapy for this indication. METHODS We enrolled adults who were being treated for bone or joint infection at 26 U.K. centers. Within 7 days after surgery (or, if the infection was being managed without surgery, within 7 days after the start of antibiotic treatment), participants were randomly assigned to receive either intravenous or oral antibiotics to complete the first 6 weeks of therapy. Follow-on oral antibiotics were permitted in both groups. The primary end point was definitive treatment failure within 1 year after randomization. In the analysis of the risk of the primary end point, the noninferiority margin was 7.5 percentage points. RESULTS Among the 1054 participants (527 in each group), end-point data were available for 1015 (96.3%). Treatment failure occurred in 74 of 506 participants (14.6%) in the intravenous group and 67 of 509 participants (13.2%) in the oral group. Missing end-point data (39 participants, 3.7%) were imputed. The intention-to-treat analysis showed a difference in the risk of definitive treatment failure (oral group vs. intravenous group) of −1.4 percentage points (90% confidence interval [CI], −4.9 to 2.2; 95% CI, −5.6 to 2.9), indicating noninferiority. Complete-case, per-protocol, and sensitivity analyses supported this result. The between-group difference in the incidence of serious adverse events was not significant (146 of 527 participants [27.7%] in the intravenous group and 138 of 527 [26.2%] in the oral group; P=0.58). Catheter complications, analyzed as a secondary end point, were more common in the intravenous group (9.4% vs. 1.0%). CONCLUSIONS Oral antibiotic therapy was noninferior to intravenous antibiotic therapy when used during the first 6 weeks for complex orthopedic infection, as assessed by treatment failure at 1 year. (Funded by the National Institute for Health Research; OVIVA Current Controlled Trials number, ISRCTN91566927. opens in new tab.

Discutindo a educação ambiental no cotidiano escolar: desenvolvimento de projetos na escola formação inicial e continuada de professores

A presente pesquisa buscou discutir como a Educação Ambiental (EA) vem sendo trabalhada, no Ensino Fundamental e como os docentes desta escola compreendem e vem inserindo a EA no cotidiano escolar., em uma escola estadual do município de Tangará da Serra/MT, Brasil. Para tanto, realizou-se entrevistas com os professores que fazem parte de um projeto interdisciplinar de EA na escola pesquisada. Verificou-se que o projeto da escola não vem conseguindo alcançar os objetivos propostos por: desconhecimento do mesmo, pelos professores; formação deficiente dos professores, não entendimento da EA como processo de ensino-aprendizagem, falta de recursos didáticos, planejamento inadequado das atividades. A partir dessa constatação, procurou-se debater a impossibilidade de tratar do tema fora do trabalho interdisciplinar, bem como, e principalmente, a importância de um estudo mais aprofundado de EA, vinculando teoria e prática, tanto na formação docente, como em projetos escolares, a fim de fugir do tradicional vínculo “EA e ecologia, lixo e horta”.Facultad de Humanidades y Ciencias de la Educació

Chemical speciation, volatilisation and cycling of 36I, 129I and 99Tc in coniferous forest systems

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Comparison of Early Outcomes for Normothermic and Hypothermic Cardiopulmonary Bypass in Children Undergoing Congenital Heart Surgery.

Objective: Comparison of early outcomes of normothermic cardiopulmonary bypass (N-CPB, ≥35°C) with hypothermic cardiopulmonary bypass (H-CPB, 28-34°C) for congenital heart defects. Methods: Data from 99 patients <2 years operated with N-CPB (n = 48) or H-CPB (n = 51) were retrospectively reviewed: aortic X-clamping and CPB duration, vasoactive inotropic score (VIS), arterial lactate, pH and base excess, urine output, extubation, PICU stay, transfusion requirements, chest drain losses, costs of transfusions, and costs of PICU stay. Results: The two groups were homogeneous for diagnosis, risk factors, surgery and demographic variables: N-CPB age 7.7 ± 6.1 months, weight 6.2 ± 2.4 kg, and H-CPB age 6.6 ± 6.5 months, weight 6.1 ± 2.4 kg. There were no hospital deaths in either group. VIS in N-CPB was lower than H-CPB on PICU arrival (9.7 ± 5.9 vs. 13.4 ± 7.9, P < 0.005), after 4 h (7.0 ± 5.2 vs. 11.1 ± 7.3, P < 0.001) and 24 h (2.8 ± 3.6 vs. 5.6 ± 5.6, P < 0.003); arterial pH was better at PICU arrival (7.33 ± 0.09 vs. 7.30 ± 0.09, P = 0.046) after 4 h (7.35 ± 0.07 vs. 7.32 ± 0.07, P = 0.022) and after 24 h (7.37 ± 0.05 vs. 7.35 ± 0.05, P = 0.01). Extubation was earlier in N-CPB than in H-CPB (22 ± 27 vs. 48 ± 57 h, P = 0.003) as PICU discharge (61 ± 46 h vs. 87 ± 69 h, P = 0.021). Transfusion requirements in operating room were lower in N-CPB vs. H-CPB for RBC, FFP, cryoprecipitate, and platelets, while during the first 24 h in PICU were lower only for cryoprecipitate and platelets. Chest drain losses (mL/kg) on PICU arrival, after 4 and 24 h were lower with N-CPB vs. H-CPB (respectively 1.5 ± 1.4 vs. 2.5 ± 2.7, P = 0.013, 7.8 ± 6.0 vs. 10.9 ± 8.7, P = 0.025, and 23.0 ± 12.0 vs. 27.9 ± 15.2, P = 0.043). Tranexamic acid infusion was required in 7/48 (14.6%) patients with N-CPB vs. 18/51(= 35.3%) in H-CPB (P = 0.009). The average total costs/patient of blood and blood products (RBC, FFP, cryoprecipitate, platelets) were lower in N-CPB vs. H-CPB for both the first 24 h after surgery (£204 ± 169 vs. £306 ± 254, P = 0.011) as well as during the total duration of PICU stay (£239 ± 193 vs. £427 ± 337, P = 0.001). The average cost/patient/day of stay in PICU was lower in N-CPB than in H-CPB (£4,067 ± 3,067 vs. £5,800 ± 4,600, P = 0.021). Conclusions: N-CPB may reduce inotropic and respiratory support, shorten PICU stay, and decrease peri-operative transfusion requirements, with subsequent costs reduction, compared to H-CPB. Future studies are needed to validate and support wider use of N-CPB