The role of macrophages and polymorphs in the levan-induced inhibition of Lewis lung carcinoma in C57BL mice.

High-mol.-wt levan injected locally inhibits the growth of Lewis lung carcinoma in C57BL mice. The inhibition is dependent on the number of tumour cells injected and on the dose of levan. The inhibition decreases tumour incidence and size as well as prolonging survival. The polysaccharide is most effective when injected daily beginning on the day of tumour-cell inoculation. Treatment begun on later dates is less effective. Treatment begun one day before tumour-cell inoculation enhances tumour growth. Histological studies showed that levan induces an intense polymorphonuclear (PMN) reaction followed by accumulation of vacuolated, levan-laden macrophages. Both PMN and activated macrophages seemed to have an inhibitory effect upon the growth of the tumour. The effector role of PMN was not explained by the histological study. Tumour cells in close contact with levan-laden macrophages appeared mostly necrotic. Administration of levan begun one day before tumour-cell inoculation produced a similar reaction, but the infiltrating cells did not appear to approach and damage the tumour cells

Early discontinuation of antibiotics for febrile neutropenia versus continuation until neutropenia resolution

Abstract Background: People with cancer with febrile neutropenia are at risk of severe infections and mortality and are thus treated empirically with broad-spectrum antibiotic therapy. However, the recommended duration of antibiotic therapy differs across guidelines. Objectives: To assess the safety of protocol-guided discontinuation of antibiotics regardless of neutrophil count, compared to continuation of antibiotics until neutropenia resolution in people with cancer with fever and neutropenia, in terms of mortality and morbidity. To assess the emergence of resistant bacteria in people with cancer treated with short courses of antibiotic therapy compared with people with cancer treated until resolution of neutropenia. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 10) in the Cochrane Library, MEDLINE, Embase, and LILACS up to 1 October 2018. We searched the metaRegister of Controlled Trials and the US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov for ongoing and unpublished trials. We reviewed the references of all identified studies for additional trials and handsearched conference proceedings of international infectious diseases and oncology and haematology conferences. Selection criteria: We included randomised controlled trials (RCTs) that compared a short antibiotic therapy course in which discontinuation of antibiotics was guided by protocols regardless of the neutrophil count to a long course in which antibiotics were continued until neutropenia resolution in people with cancer with febrile neutropenia. The primary outcome was 30-day or end of follow-up all-cause mortality. Data collection and analysis: Two review authors independently reviewed all studies for eligibility, extracted data, and assessed risk of bias for all included trials. We calculated risk ratios (RRs) with 95% confidence intervals (CIs) whenever possible. For dichotomous outcomes with zero events in both arms of the trials, we conducted meta-analysis of risk differences (RDs) as well. For continuous outcomes, we extracted means with standard deviations (SD) from the studies and computed mean difference (MD) and 95% CI. If no substantial clinical heterogeneity was found, trials were pooled using the Mantel-Haenszel fixed-effect model. Main results: We included eight RCTs comprising a total of 662 distinct febrile neutropenia episodes. The studies included adults and children, and had variable design and criteria for discontinuation of antibiotics in both study arms. All included studies but two were performed before the year 2000. All studies included people with cancer with fever of unknown origin and excluded people with microbiological documented infections.We found no significant difference between the short-antibiotic therapy arm and the long-antibiotic therapy arm for all-cause mortality (RR 1.38, 95% CI 0.73 to 2.62; RD 0.02, 95% CI -0.02 to 0.05; low-certainty evidence). We downgraded the certainty of the evidence to low due to imprecision and high risk of selection bias. The number of fever days was significantly lower for people in the short-antibiotic treatment arm compared to the long-antibiotic treatment arm (mean difference -0.64, 95% CI -0.96 to -0.32; I² = 30%). In all studies, total antibiotic days were fewer in the intervention arm by three to seven days compared to the long antibiotic therapy. We found no significant differences in the rates of clinical failure (RR 1.23, 95% CI 0.85 to 1.77; very low-certainty evidence). We downgraded the certainty of the evidence for clinical failure due to variable and inconsistent definitions of clinical failure across studies, possible selection bias, and wide confidence intervals. There was no significant difference in the incidence of bacteraemia occurring after randomisation (RR 1.56, 95% CI 0.91 to 2.66; very low-certainty evidence), while the incidence of any documented infections was significantly higher in the short-antibiotic therapy arm (RR 1.67, 95% CI 1.08 to 2.57). There was no significant difference in the incidence of invasive fungal infections (RR 0.86, 95% CI 0.32 to 2.31) and development of antibiotic resistance (RR 1.49, 95% CI 0.62 to 3.61). The data on hospital stay were too sparse to permit any meaningful conclusions. Authors' conclusions: We could make no strong conclusions on the safety of antibiotic discontinuation before neutropenia resolution among people with cancer with febrile neutropenia based on the existing evidence and its low certainty. Results of microbiological outcomes favouring long antibiotic therapy may be misleading due to lower culture positivity rates under antibiotic therapy and not true differences in infection rates. Well-designed, adequately powered RCTs are required that address this issue in the era of rising antibiotic resistance

Full meta objects for flexible geoprocessing workflows: profiling WPS or BPMN?

The design and execution of scientific workflows is an important and necessary function within many disciplines. In the geospatial community, workflows are used to generate and quality assure new spatial datasets based on sequences of processing steps or complex modelling. Using BPMN for representing these workflows allows stakeholders to discuss the scientific conceptual approach behind this modelling whilst also being able to execute its encoding in XML. Previous research has focused on developing frameworks, including a BPMN workflow engine, capable of orchestrating OGC Web Processing Services and thus enabling construction of interoperable workflows comprised of distributed resources. These could populate, for example, the GEOSS repository. However, to date, such work has focused on executing workflows with direct access to the pre-defined data inputs and outputs, with a lack of flexibility and efficiency in semantic interoperability or data management during composition and execution. This article suggests a meta-approach based on two possible configurations that enable workflow orchestration at a meta level using a direct coupling with a metadata catalogue. The designs of a Web Processing Service profile and of a BPMN profile are presented as potential approaches to abstract the data interchange between the processing steps of a workflow. The paper concludes with a discussion of how these approaches may be extended and how complete workflows might be registered and managed using catalogues services

Red and processed meat consumption and purchasing behaviours and attitudes: impacts for human health, animal welfare and environmental sustainability

Objective: Higher intakes of red and processed meat are associated with poorer health outcomes and negative environmental impacts. Drawing upon a population survey the present paper investigates meat consumption behaviours, exploring perceived impacts for human health, animal welfare and the environment. Design: Structured self-completion postal survey relating to red and processed meat, capturing data on attitudes, sustainable meat purchasing behaviour, red and processed meat intake, plus sociodemographic characteristics of respondents. Setting: Urban and rural districts of Nottinghamshire, East Midlands, UK, drawn from the electoral register. Subjects: UK adults (n 842) aged 18–91 years, 497 females and 345 males, representing a 35·6 % response rate from 2500 randomly selected residents. Results: Women were significantly more likely (P 60 years) were more likely to hold positive attitudes towards animal welfare (P<0·01). Less than a fifth (18·4 %) of the sample agreed that the impact of climate change could be reduced by consuming less meat, dairy products and eggs. Positive attitudes towards animal welfare were associated with consuming less meat and a greater frequency of ‘higher welfare’ meat purchases. Conclusions: Human health and animal welfare are more common motivations to avoid red and processed meat than environmental sustainability. Policy makers, nutritionists and health professionals need to increase the public’s awareness of the environmental impact of eating red and processed meat. A first step could be to ensure that dietary guidelines integrate the nutritional, animal welfare and environmental components of sustainable diets

Corticosteroids for pneumonia

BackgroundPneumonia is a common and potentially serious illness. Corticosteroids have been suggested for the treatment of different types of infection, however their role in the treatment of pneumonia remains unclear. This is an update of a review published in 2011.ObjectivesTo assess the efficacy and safety of corticosteroids in the treatment of pneumonia.Search methodsWe searched the Cochrane Acute Respiratory Infections Group's Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS on 3March 2017, together with relevant conference proceedings and references of identified trials. We also searched three trials registers for ongoing and unpublished trials.Selection criteriaWe included randomised controlled trials (RCTs) that assessed systemic corticosteroid therapy, given as adjunct to antibiotic treatment, versus placebo or no corticosteroids for adults and children with pneumonia.Data collection and analysisWe used standard methodological procedures expected by Cochrane. Two review authors independently assessed risk of bias and extracted data. We contacted study authors for additional information. We estimated risk ratios (RR) with 95% confidence intervals (CI) and pooled data using the Mantel-Haenszel fixed-effect model when possible.Main resultsWe included 17 RCTs comprising a total of 2264 participants; 13 RCTs included 1954 adult participants, and four RCTs included 310 children. This update included 12 new studies, excluded one previously included study, and excluded five new trials. One trial awaits classification.All trials limited inclusion to inpatients with community-acquired pneumonia (CAP), with or without healthcare-associated pneumonia (HCAP). We assessed the risk of selection bias and attrition bias as low or unclear overall. We assessed performance bias risk as low for nine trials, unclear for one trial, and high for seven trials. We assessed reporting bias risk as low for three trials and high for the remaining 14 trials.Corticosteroids significantly reduced mortality in adults with severe pneumonia (RR 0.58, 95% CI 0.40 to 0.84; moderate-quality evidence), but not in adults with non-severe pneumonia (RR 0.95, 95% CI 0.45 to 2.00). Early clinical failure rates (defined as death from any cause, radiographic progression, or clinical instability at day 5 to 8) were significantly reduced with corticosteroids in people with severe and non-severe pneumonia (RR 0.32, 95% CI 0.15 to 0.7; and RR 0.68, 95% CI 0.56 to 0.83, respectively; high-quality evidence). Corstocosteroids reduced time to clinical cure, length of hospital and intensive care unit stays, development of respiratory failure or shock not present at pneumonia onset, and rates of pneumonia complications.Among children with bacterial pneumonia, corticosteroids reduced early clinical failure rates (defined as for adults, RR 0.41, 95% CI 0.24 to 0.70; high-quality evidence) based on two small, clinically heterogeneous trials, and reduced time to clinical cure.Hyperglycaemia was significantly more common in adults treated with corticosteroids (RR 1.72, 95% CI 1.38 to 2.14). There were no significant differences between corticosteroid-treated people and controls for other adverse events or secondary infections (RR 1.19, 95% CI 0.73 to 1.93).Authors' conclusionsCorticosteroid therapy reduced mortality and morbidity in adults with severe CAP; the number needed to treat for an additional beneficial outcome was 18 patients (95% CI 12 to 49) to prevent one death. Corticosteroid therapy reduced morbidity, but not mortality, for adults and children with non-severe CAP. Corticosteroid therapy was associated with more adverse events, especially hyperglycaemia, but the harms did not seem to outweigh the benefits

Addressing resistance to antibiotics in systematic reviews of antibiotic interventions

Antibiotics are among the most important interventions in healthcare. Resistance of bacteria to antibiotics threatens the effectiveness of treatment. Systematic reviews of antibiotic treatments often do not address resistance to antibiotics even when data are available in the original studies. This omission creates a skewed view, which emphasizes short-term efficacy and ignores the long-term consequences to the patient and other people. We offer a framework for addressing antibiotic resistance in systematic reviews. We suggest that the data on background resistance in the original trials should be reported and taken into account when interpreting results. Data on emergence of resistance (whether in the body reservoirs or in the bacteria causing infection) are important outcomes. Emergence of resistance should be taken into account when interpreting the evidence on antibiotic treatment in randomized controlled trials or systematic reviews

Retrospective observational study to assess the clinical management and outcomes of hospitalised patients with complicated urinary tract infection in countries with high prevalence of multidrug resistant Gram-negative bacteria (RESCUING)

INTRODUCTION: The emergence of multidrug resistant (MDR) Gram-negative bacteria (GNB), including carbapenemase-producing strains, has become a major therapeutic challenge. These MDR isolates are often involved in complicated urinary tract infection (cUTI), and are associated with poor clinical outcomes. The study has been designed to gain insight into the epidemiology, clinical management, outcome and healthcare cost of patients with cUTI, especially in countries with high prevalence of MDR GNB. METHODS AND ANALYSIS: This multinational and multicentre observational, retrospective study will identify cases from 1 January 2013 to 31 December 2014 in order to collect data on patients with cUTI as a cause of hospital admission, and patients who develop cUTI during their hospital stay. The primary end point will be treatment failure defined as the presence of any of the following criteria: (1) signs or symptoms of cUTI present at diagnosis that have not improved by days 5–7 with appropriate antibiotic therapy, (2) new cUTI-related symptoms that have developed within 30 days of diagnosis, (3) urine culture taken within 30 days of diagnosis, either during or after completion of therapy, that grows ≥104 colony-forming unit/mL of the original pathogen and (4) death irrespective of cause within 30 days of the cUTI diagnosis. SAMPLE SIZE: 1000 patients afford a power of 0.83 (α=0.05) to detect an absolute difference of 10% in the treatment failure rate between MDR bacteria and other pathogens. This should allow for the introduction of about 20 independent risk factors (or their interaction) in a logistic regression model looking at risk factors for failure. ETHICS AND DISSEMINATION: Approval will be sought from all relevant Research Ethics Committees. Publication of this study will be considered as a joint publication by the participating investigator leads, and will follow the recommendations of the International Committee of Medical Journal Editors (ICMJE)