How different data sources and definitions of neighbourhood influence the association between food outlet availability and body mass index: a cross-sectional study.

Inconsistencies in methodologies continue to inhibit understanding of the impact of the environment on body mass index (BMI). To estimate the effect of these differences, we assessed the impact of using different definitions of neighbourhood and data sets on associations between food outlet availability within the environment and BMI. Previous research has not extended this to show any differences in the strength of associations between food outlet availability and BMI across both different definitions of neighbourhood and data sets. Descriptive statistics showed differences in the number of food outlets, particularly other food retail outlets between different data sets and definitions of neighbourhood. Despite these differences, our key finding was that across both different definitions of neighbourhood and data sets, there was very little difference in size of associations between food outlets and BMI. Researchers should consider and transparently report the impact of methodological choices such as the definition of neighbourhood and acknowledge any differences in associations between the food environment and BMI

Validation of a Dutch Risk Score Predicting Poor Outcome in Adults with Bacterial Meningitis in Vietnam and Malawi

We have previously developed and validated a prognostic model to predict the risk for unfavorable outcome in Dutch adults with bacterial meningitis. The aim of the current study was to validate this model in adults with bacterial meningitis from two developing countries, Vietnam and Malawi. Demographic and clinical characteristics of Vietnamese (n = 426), Malawian patients (n = 465) differed substantially from those of Dutch patients (n = 696). The Dutch model underestimated the risk of poor outcome in both Malawi and Vietnam. The discrimination of the original model (c-statistic [c] 0.84; 95% confidence interval 0.81 to 0.86) fell considerably when re-estimated in the Vietnam cohort (c = 0.70) or in the Malawian cohort (c = 0.68). Our validation study shows that new prognostic models have to be developed for these countries in a sufficiently large series of unselected patients

The management of Staphylococcus aureus bacteremia in the United Kingdom and Vietnam: a multi-centre evaluation.

Background: Staphylococcus aureus bacteremia is a common and serious infection worldwide and although treatment guidelines exist, there is little consensus on optimal management. In this study we assessed the variation in management and adherence to treatment guidelines of S. aureus bacteremia. Methodology/Principal Findings: We prospectively recorded baseline clinical characteristics, management, and in-hospital outcome of all adults with S. aureus bacteremia treated consecutively over one year in eight centres in the United Kingdom, three in Vietnam and one in Nepal. 630 adults were treated for S. aureus bacteremia: 549 in the UK (21% methicillin-resistant), 80 in Vietnam (19% methicillin-resistant) and 1 in Nepal. In the UK, 41% had a removable infection focus (50% intravenous catheter-related), compared to 12% in Vietnam. Significantly (p50% of treatment with oral antibiotics alone (25% versus 4%). UK centres varied significantly (p50% of treatment (range 12-40%), in those treated for longer than 28 days (range 13-54%), and in those given combination therapy (range 14-94%). 24% died during admission: older age, time in hospital before bacteremia, and an unidentified infection focus were independent predictors of in-hospital death (p<0.001). Conclusions/Significance: The management of S. aureus bacteremia varies widely between the UK and Vietnam and between centres in the UK with little adherence to published guidelines. Controlled trials defining optimal therapy are urgently required

Epstein-Barr Virus Coinfection in Cerebrospinal Fluid Is Associated With Increased Mortality in Malawian Adults With Bacterial Meningitis

Mortality from adult bacterial meningitis exceeds 50% in sub-Saharan Africa. We postulated that—particularly in individuals infected with human immunodeficiency virus (HIV)—herpes simplex virus, varicella zoster virus, Epstein-Barr virus (EBV), and cytomegalovirus (CMV) in the cerebrospinal fluid (CSF) contribute to poor outcome. CSF from 149 Malawian adults with bacterial meningitis and 39 controls were analyzed using polymerase chain reaction. EBV was detected in 79 of 149 bacterial meningitis patients. Mortality (54%) was associated with higher CSF EBV load when adjusted for HIV (P = .01). CMV was detected in 11 of 115 HIV-infected patients, 8 of whom died. The mechanisms by which EBV and CMV contribute to poor outcome require further investigation

To what extent can decommissioning options for marine artificial structures move us toward environmental targets?

Switching from fossil fuels to renewable energy is key to international energy transition efforts and the move toward net zero. For many nations, this requires decommissioning of hundreds of oil and gas infrastructure in the marine environment. Current international, regional and national legislation largely dictates that structures must be completely removed at end-of-life although, increasingly, alternative decommissioning options are being promoted and implemented. Yet, a paucity of real-world case studies describing the impacts of decommissioning on the environment make decision-making with respect to which option(s) might be optimal for meeting international and regional strategic environmental targets challenging. To address this gap, we draw together international expertise and judgment from marine environmental scientists on marine artificial structures as an alternative source of evidence that explores how different decommissioning options might ameliorate pressures that drive environmental status toward (or away) from environmental objectives. Synthesis reveals that for 37 United Nations and Oslo-Paris Commissions (OSPAR) global and regional environmental targets, experts consider repurposing or abandoning individual structures, or abandoning multiple structures across a region, as the options that would most strongly contribute toward targets. This collective view suggests complete removal may not be best for the environment or society. However, different decommissioning options act in different ways and make variable contributions toward environmental targets, such that policy makers and managers would likely need to prioritise some targets over others considering political, social, economic, and ecological contexts. Current policy may not result in optimal outcomes for the environment or society

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

Antimicrobial resistance determinants are associated with Staphylococcus aureus bacteraemia and adaptation to the healthcare environment: a bacterial genome-wide association study

Staphylococcus aureus is a major bacterial pathogen in humans, and a dominant cause of severe bloodstream infections. Globally, antimicrobial resistance (AMR) in S. aureus remains challenging. While human risk factors for infection have been defined, contradictory evidence exists for the role of bacterial genomic variation in S. aureus disease. To investigate the contribution of bacterial lineage and genomic variation to the development of bloodstream infection, we undertook a genome-wide association study comparing bacteria from 1017 individuals with bacteraemia to 984 adults with asymptomatic S. aureus nasal carriage. Within 984 carriage isolates, we also compared healthcare-associated (HA) carriage with community-associated (CA) carriage. All major global lineages were represented in both bacteraemia and carriage, with no evidence for different infection rates. However, kmers tagging trimethoprim resistance-conferring mutation F99Y in dfrB were significantly associated with bacteraemia-vs-carriage (P=10-8.9-10-9.3). Pooling variation within genes, bacteraemia-vs-carriage was associated with the presence of mecA (HMP=10-5.3) as well as the presence of SCCmec (HMP=10-4.4). Among S. aureus carriers, no lineages were associated with HA-vs-CA carriage. However, we found a novel signal of HA-vs-CA carriage in the foldase protein prsA, where kmers representing conserved sequence allele were associated with CA carriage (P=10-7.1-10-19.4), while in gyrA, a ciprofloxacin resistance-conferring mutation, L84S, was associated with HA carriage (P=10-7.2). In an extensive study of S. aureus bacteraemia and nasal carriage in the UK, we found strong evidence that all S. aureus lineages are equally capable of causing bloodstream infection, and of being carried in the healthcare environment. Genomic variation in the foldase protein prsA is a novel genomic marker of healthcare origin in S. aureus but was not associated with bacteraemia. AMR determinants were associated with both bacteraemia and healthcare-associated carriage, suggesting that AMR increases the propensity not only to survive in healthcare environments, but also to cause invasive disease

Priorities for synthesis research in ecology and environmental science

ACKNOWLEDGMENTS We thank the National Science Foundation grant #1940692 for financial support for this workshop, and the National Center for Ecological Analysis and Synthesis (NCEAS) and its staff for logistical support.Peer reviewedPublisher PD

Priorities for synthesis research in ecology and environmental science

ACKNOWLEDGMENTS We thank the National Science Foundation grant #1940692 for financial support for this workshop, and the National Center for Ecological Analysis and Synthesis (NCEAS) and its staff for logistical support.Peer reviewedPublisher PD