The Community IntraVenous Antibiotic Study (CIVAS): a mixed methods evaluation of patient preferences for and cost effectiveness of different service models for delivering outpatient parenteral antimicrobial therapy

Background: Outpatient parenteral antimicrobial therapy (OPAT) is widely used in most developed countries, providing considerable opportunities for improved cost savings. However, it is implemented only partially in the UK, using a variety of service models. Objectives: The aims of this research were to (1) establish the extent of OPAT service models in England and identify their development; (2) evaluate patients’ preferences for different OPAT service delivery models; (3) assess the cost-effectiveness of different OPAT service delivery models; and (4) convene a consensus panel to consider our evidence and make recommendations. Methods: This mixed-methods study included seven centres providing OPAT using four main service models: (1) hospital outpatient (HO) attendance; (2) specialist nurse (SN) visiting at home; (3) general nurse (GN) visiting at home; and (4) self-administration (SA) or carer administration. Health-care providers were surveyed and interviewed to explore the implementation of OPAT services in England. OPAT patients were interviewed to determine key service attributes to develop a discrete choice experiment (DCE). This was used to perform a quantitative analysis of their preferences and attitudes. Anonymised OPAT case data were used to model cost-effectiveness with both Markov and simulation modelling methods. An expert panel reviewed the evidence and made recommendations for future service provision and further research. Results: The systematic review revealed limited robust literature but suggested that HO is least effective and SN is most effective. Qualitative study participants felt that different models of care were suited to different types of patient and they also identified key service attributes. The DCE indicated that type of service was the most important factor, with SN being strongly preferred to HO and SA. Preferences were influenced by attitudes to health care. The results from both Markov and simulation models suggest that a SN model is the optimal service for short treatment courses (up to 7 days). Net monetary benefit (NMB) values for HO, GN and SN services were £2493, £2547 and £2655, respectively. For longer treatment, SA appears to be optimal, although SNs provide slightly higher benefits at increased cost. NMB values for HO, GN, SN and SA services were £8240, £9550, £10,388 and £10,644, respectively. The simulation model provided useful information for planning OPAT services. The expert panel requested more guidance for service providers and commissioners. Overall, they agreed that mixed service models were preferable. Limitations: Recruitment to the qualitative study was suboptimal in the very elderly and ethnic minorities, so the preferences of patients from these groups might not be represented. The study recruited from Yorkshire, so the findings may not be applicable nationally. Conclusions: The quantitative preference analysis and economic modelling favoured a SN model, although there are differences between sociodemographic groups. SA provides cost savings for long-term treatment but is not appropriate for all. Future work: Further research is necessary to replicate our results in other regions and populations and to evaluate mixed service models. The simulation modelling and DCE methods used here may be applicable in other health-care settings. Funding: The National Institute for Health Research Health Service and Delivery Research programme

A behavioral database for masked form priming

Reading involves a process of matching an orthographic input with stored representations in lexical memory. The masked priming paradigm has become a standard tool for investigating this process. Use of existing results from this paradigm can be limited by the precision of the data and the need for cross-experiment comparisons that lack normal experimental controls. Here, we present a single, large, high-precision, multicondition experiment to address these problems. Over 1,000 participants from 14 sites responded to 840 trials involving 28 different types of orthographically related primes (e.g., castfe–CASTLE) in a lexical decision task, as well as completing measures of spelling and vocabulary. The data were indeed highly sensitive to differences between conditions: After correction for multiple comparisons, prime type condition differences of 2.90 ms and above reached significance at the 5% level. This article presents the method of data collection and preliminary findings from these data, which included replications of the most widely agreed-upon differences between prime types, further evidence for systematic individual differences in susceptibility to priming, and new evidence regarding lexical properties associated with a target word’s susceptibility to priming. These analyses will form a basis for the use of these data in quantitative model fitting and evaluation and for future exploration of these data that will inform and motivate new experiments

Macrophage phenotype is associated with disease severity in preterm infants with chronic lung disease.

The etiology of persistent lung inflammation in preterm infants with chronic lung disease of prematurity (CLD) is poorly characterized, hampering efforts to stratify prognosis and treatment. Airway macrophages are important innate immune cells with roles in both the induction and resolution of tissue inflammation

Energy expenditure of acutely ill hospitalised patients

OBJECTIVE: To measure energy expenditure of acutely ill elderly patients in hospital and following discharge in the community. DESIGN: Sixty-three consecutive hospitalised acutely ill elderly patients were recruited. Eight patients were studied to assess the reliability of the Delta Tract Machine as a measure of energy expenditure; 35 patients had their energy expenditure studied in hospital on two occasions and 20 patients had their energy expenditure measured in hospital and at 6 weeks in the community RESULTS: Men had higher basal energy expenditure (BMR) values compared to women however the difference was not statistically significant [Men, mean (SD) 1405 (321) Kcal, women 1238 (322) kcal; mean difference (95% CI) 166 kcal (-17 to 531), p = 0.075]. After adjusting for age, gender and body mass index both medication and C-reactive protein (CRP), concentrations showed significant correlation with measured energy expenditure in hospital, (r = -0.36, "p < 0.05"; r = -0.29, "p < 0.05" respectively). However, in a multivariate analysis for all 63 subjects combined CRP explained most of the variance in BMR in hospital. The Harris Benedict equation predicted within ± 10% measured BMR in only 47% of individuals in hospital. CONCLUSION: Tissue inflammation and medications were associated with change in measured energy expenditure in acutely ill patients

Search for rare quark-annihilation decays, B --> Ds(*) Phi

We report on searches for B- --> Ds- Phi and B- --> Ds*- Phi. In the context of the Standard Model, these decays are expected to be highly suppressed since they proceed through annihilation of the b and u-bar quarks in the B- meson. Our results are based on 234 million Upsilon(4S) --> B Bbar decays collected with the BABAR detector at SLAC. We find no evidence for these decays, and we set Bayesian 90% confidence level upper limits on the branching fractions BF(B- --> Ds- Phi) Ds*- Phi)<1.2x10^(-5). These results are consistent with Standard Model expectations.Comment: 8 pages, 3 postscript figues, submitted to Phys. Rev. D (Rapid Communications

Perspectives and Integration in SOLAS Science

Why a chapter on Perspectives and Integration in SOLAS Science in this book? SOLAS science by its nature deals with interactions that occur: across a wide spectrum of time and space scales, involve gases and particles, between the ocean and the atmosphere, across many disciplines including chemistry, biology, optics, physics, mathematics, computing, socio-economics and consequently interactions between many different scientists and across scientific generations. This chapter provides a guide through the remarkable diversity of cross-cutting approaches and tools in the gigantic puzzle of the SOLAS realm. Here we overview the existing prime components of atmospheric and oceanic observing systems, with the acquisition of ocean–atmosphere observables either from in situ or from satellites, the rich hierarchy of models to test our knowledge of Earth System functioning, and the tremendous efforts accomplished over the last decade within the COST Action 735 and SOLAS Integration project frameworks to understand, as best we can, the current physical and biogeochemical state of the atmosphere and ocean commons. A few SOLAS integrative studies illustrate the full meaning of interactions, paving the way for even tighter connections between thematic fields. Ultimately, SOLAS research will also develop with an enhanced consideration of societal demand while preserving fundamental research coherency. The exchange of energy, gases and particles across the air-sea interface is controlled by a variety of biological, chemical and physical processes that operate across broad spatial and temporal scales. These processes influence the composition, biogeochemical and chemical properties of both the oceanic and atmospheric boundary layers and ultimately shape the Earth system response to climate and environmental change, as detailed in the previous four chapters. In this cross-cutting chapter we present some of the SOLAS achievements over the last decade in terms of integration, upscaling observational information from process-oriented studies and expeditionary research with key tools such as remote sensing and modelling. Here we do not pretend to encompass the entire legacy of SOLAS efforts but rather offer a selective view of some of the major integrative SOLAS studies that combined available pieces of the immense jigsaw puzzle. These include, for instance, COST efforts to build up global climatologies of SOLAS relevant parameters such as dimethyl sulphide, interconnection between volcanic ash and ecosystem response in the eastern subarctic North Pacific, optimal strategy to derive basin-scale CO2 uptake with good precision, or significant reduction of the uncertainties in sea-salt aerosol source functions. Predicting the future trajectory of Earth’s climate and habitability is the main task ahead. Some possible routes for the SOLAS scientific community to reach this overarching goal conclude the chapter

The influence of early aging on eye movements during motor simulation

Movement based interventions such as imagery and action observation are used increasingly to support physical rehabilitation of adults during early aging. The efficacy of these more covert approaches is based on an intuitively appealing assumption that movement execution, imagery and observation share neural substrate; alteration of one influences directly the function of the other two. Using eye movement metrics this paper reports findings that question the congruency of the three conditions. The data reveal that simulating movement through imagery and action observation may offer older adults movement practice conditions that are not constrained by the age-related decline observed in physical conditions. In addition, the findings provide support for action observation as a more effective technique for movement reproduction in comparison to imagery. This concern for imagery was also seen in the less congruent temporal relationship in movement time between imagery and movement execution suggesting imagery inaccuracy in early aging

Evidence of Combat in Triceratops

Background: The horns and frill of Triceratops and other ceratopsids (horned dinosaurs) are interpreted variously as display structures or as weapons against conspecifics and predators. Lesions (in the form of periosteal reactive bone, healing fractures, and alleged punctures) on Triceratops skulls have been used as anecdotal support of intraspecific combat similar to that in modern horned and antlered animals. If ceratopsids with different cranial morphologies used their horns in such combat, this should be reflected in the rates of lesion occurrence across the skull. Methodology/Principal Findings: We used a G-test of independence to compare incidence rates of lesions in Triceratops (which possesses two large brow horns and a smaller nasal horn) and the related ceratopsid Centrosaurus (with a large nasal horn and small brow horns), for the nasal, jugal, squamosal, and parietal bones of the skull. The two taxa differ significantly in the occurrence of lesions on the squamosal bone of the frill (P = 0.002), but not in other cranial bones (P.0.20). Conclusions/Significance: This pattern is consistent with Triceratops using its horns in combat and the frill being adapted as a protective structure for this taxon. Lower pathology rates in Centrosaurus may indicate visual rather than physical use o

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Urban spaces, fragmented consciousness, and indecipherable meaning in Mrs Dalloway

This essay discusses the importance of urban spaces in Virginia Woolf's Mrs Dalloway, linking them to central themes in the novel (including the fragmented consciousness of the characters, and withheld - or only partially understood - meaning)