Cost-effectiveness analysis of preoperative transfusion in patients with sickle cell disease using evidence from the TAPS trial.

The study's objective was to assess the cost-effectiveness of preoperative transfusion compared with no preoperative transfusion in patients with sickle cell disease undergoing low- or medium-risk surgery. Seventy patients with sickle cell disease (HbSS/Sß(0) thal genotypes) undergoing elective surgery participated in a multicentre randomised trial, Transfusion Alternatives Preoperatively in Sickle Cell Disease (TAPS). Here, a cost-effectiveness analysis based on evidence from that trial is presented. A decision-analytic model is used to incorporate long-term consequences of transfusions and acute chest syndrome. Costs and health benefits, expressed as quality-adjusted life years (QALYs), are reported from the 'within-trial' analysis and for the decision-analytic model. The probability of cost-effectiveness for each form of management is calculated taking into account the small sample size and other sources of uncertainty. In the range of scenarios considered in the analysis, preoperative transfusion was more effective, with the mean improvement in QALYs ranging from 0.018 to 0.206 per patient, and also less costly in all but one scenario, with the mean cost difference ranging from -£813 to £26. All scenarios suggested preoperative transfusion had a probability of cost-effectiveness >0.79 at a cost-effectiveness threshold of £20 000 per QALY

Mathematical modelling for antibiotic resistance control policy: do we know enough?

Background: Antibiotics remain the cornerstone of modern medicine. Yet there exists an inherent dilemma in their use: we are able to prevent harm by administering antibiotic treatment as necessary to both humans and animals, but we must be mindful of limiting the spread of resistance and safeguarding the efficacy of antibiotics for current and future generations. Policies that strike the right balance must be informed by a transparent rationale that relies on a robust evidence base. Main text: One way to generate the evidence base needed to inform policies for managing antibiotic resistance is by using mathematical models. These models can distil the key drivers of the dynamics of resistance transmission from complex infection and evolutionary processes, as well as predict likely responses to policy change in silico. Here, we ask whether we know enough about antibiotic resistance for mathematical modelling to robustly and effectively inform policy. We consider in turn the challenges associated with capturing antibiotic resistance evolution using mathematical models, and with translating mathematical modelling evidence into policy. Conclusions: We suggest that in spite of promising advances, we lack a complete understanding of key principles. From this we advocate for priority areas of future empirical and theoretical research

Roadmaps to Utopia: Tales of the Smart City

Notions of the Smart City are pervasive in urban development discourses. Various frameworks for the development of smart cities, often conceptualized as roadmaps, make a number of implicit claims about how smart city projects proceed but the legitimacy of those claims is unclear. This paper begins to address this gap in knowledge. We explore the development of a smart transport application, MotionMap, in the context of a £16M smart city programme taking place in Milton Keynes, UK. We examine how the idealized smart city narrative was locally inflected, and discuss the differences between the narrative and the processes and outcomes observed in Milton Keynes. The research shows that the vision of data-driven efficiency outlined in the roadmaps is not universally compelling, and that different approaches to the sensing and optimization of urban flows have potential for empowering or disempowering different actors. Roadmaps tend to emphasize the importance of delivering quick practical results. However, the benefits observed in Milton Keynes did not come from quick technical fixes but from a smart city narrative that reinforced existing city branding, mobilizing a growing network of actors towards the development of a smart region. Further research is needed to investigate this and other smart city developments, the significance of different smart city narratives, and how power relationships are reinforced and constructed through them

Human neutrophil clearance of bacterial pathogens triggers anti-microbial gamma delta T cell responses in early infection

Human blood Vc9/Vd2 T cells, monocytes and neutrophils share a responsiveness toward inflammatory chemokines and are rapidly recruited to sites of infection. Studying their interaction in vitro and relating these findings to in vivo observations in patients may therefore provide crucial insight into inflammatory events. Our present data demonstrate that Vc9/Vd2 T cells provide potent survival signals resulting in neutrophil activation and the release of the neutrophil chemoattractant CXCL8 (IL-8). In turn, Vc9/Vd2 T cells readily respond to neutrophils harboring phagocytosed bacteria, as evidenced by expression of CD69, interferon (IFN)-c and tumor necrosis factor (TNF)-a. This response is dependent on the ability of these bacteria to produce the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), requires cell-cell contact of Vc9/Vd2 T cells with accessory monocytes through lymphocyte function-associated antigen-1 (LFA-1), and results in a TNF-a dependent proliferation of Vc9/Vd2 T cells. The antibiotic fosmidomycin, which targets the HMB-PP biosynthesis pathway, not only has a direct antibacterial effect on most HMB-PP producing bacteria but also possesses rapid anti-inflammatory properties by inhibiting cd T cell responses in vitro. Patients with acute peritoneal-dialysis (PD)-associated bacterial peritonitis – characterized by an excessive influx of neutrophils and monocytes into the peritoneal cavity – show a selective activation of local Vc9/Vd2 T cells by HMB-PP producing but not by HMB-PP deficient bacterial pathogens. The cd T celldriven perpetuation of inflammatory responses during acute peritonitis is associated with elevated peritoneal levels of cd T cells and TNF-a and detrimental clinical outcomes in infections caused by HMB-PP positive microorganisms. Taken together, our findings indicate a direct link between invading pathogens, neutrophils, monocytes and microbe-responsive cd T cells in early infection and suggest novel diagnostic and therapeutic approaches.Martin S. Davey, Chan-Yu Lin, Gareth W. Roberts, Sinéad Heuston, Amanda C. Brown, James A. Chess, Mark A. Toleman, Cormac G.M. Gahan, Colin Hill, Tanya Parish, John D. Williams, Simon J. Davies, David W. Johnson, Nicholas Topley, Bernhard Moser and Matthias Eber

Toxigenic Clostridium difficile colonization among hospitalised adults; risk factors and impact on survival

Objectives: To establish risk factors for Clostridium difficile colonization among hospitalized patients in England. Methods: Patients admitted to elderly medicine wards at three acute hospitals in England were recruited to a prospective observational study. Participants were asked to provide a stool sample as soon as possible after enrolment and then weekly during their hospital stay. Samples were cultured for C. difficile before ribotyping and toxin detection by PCR. A multivariable logistic regression model of risk factors for C. difficile colonization was fitted from univariable risk factors significant at the p < 0.05 level. Results: 410/727 participants submitted ≥1 stool sample and 40 (9.8%) carried toxigenic C. difficile in the first sample taken. Ribotype 106 was identified three times and seven other ribotypes twice. No ribotype 027 strains were identified. Independent predictors of colonization were previous C. difficile infection (OR 4.53 (95% C.I. 1.33–15.48) and malnutrition (MUST score ≥2) (OR 3.29 (95% C.I. 1.47–7.35)). Although C. difficile colonised patients experienced higher 90-day mortality, colonization was not an independent risk for death. Conclusions: In a non-epidemic setting patients who have previously had CDI and have a MUST score of ≥2 are at increased risk of C. difficile colonization and could be targeted for active surveillance to prevent C. difficile transmission

Best practice standards for the delivery of NHS infection services in the United Kingdom

Infection expertise in the NHS has historically been provided predominantly by hospital-based medical microbiologists responsible for provision of diagnostic services and advice to front-line clinicians. While most hospitals had consultant-led microbiology departments, infectious iiseases departments were based in a small number of specialist centres. The demand for infection expertise is growing in the NHS, driven by advances in medical care, increasing awareness of the impact of antibiotic resistant and healthcare associated infections and threats from emerging infectious diseases. At the same time diagnostic services are being reorganised into pathology networks. The Combined Infection Training (CIT) is delivering a consultant workforce with expertise both in laboratory diagnostic practice and delivery of direct patient care. These changes create challenges for delivery of high quality infection expertise equitably across the NHS. They also offer an opportunity to shape infection services to meet clinical and laboratory demands.To date there has not been an attempt to bring together a single set of best practice guidelines for the requirements of an infection service. This document sets out seven standards. These are written to be practical and flexible according to the diverse ways in which infection expertise may be required across the NHS. It has been prepared by the Clinical Services Committee of the British Infection Association drawing on published evidence and guidance where they exist and on the group’s extensive experience of delivering infection services in hospitals across the NHS. It was then refined with input from the RCP Joint Specialist committee (JSC) and the RCPath Specialist Advisory Committee (SAC) and through consultation with the RCPath membership. It has been endorsed by the Royal College of Pathologists and the Royal College of Physicians. It will be reviewed annually by the CSC and updated as additional evidence becomes available

Seabed morphology and bed shear stress predict temperate reef habitats in a high energy marine region

High energy marine regions host ecologically important habitats like temperate reefs, but are less anthropogenically developed and understudied compared to lower energy waters. In the marine environment direct habitat observation is limited to small spatial scales, and high energy waters present additional logistical challenges and constraints. Semi-automated predictive habitat mapping is a cost-effective tool to map benthic habitats across large extents, but performance is context specific. High resolution environmental data used for predictive mapping are often limited to bathymetry, acoustic backscatter and their derivatives. However, hydrodynamic energy at the seabed is a critical habitat structuring factor and likely an important, yet rarely incorporated, predictor of habitat composition and spatial patterning. Here, we used a machine learning classification approach to map temperate reef substrate and biogenic reef habitat in a tidal energy development area, incorporating bathymetric derivatives at multiple scales and simulated tidally induced seabed shear stress. We mapped reef substrate (four classes: sediment (not reef), stony reef (low resemblance), stony reef (medium – high resemblance) and bedrock reef) with overall balanced accuracy of 71.7%. Our model to predict potential biogenic Sabellaria spinulosa reef performed less well with an overall balanced accuracy of 63.4%. Despite low performance metrics for the target class of potential reef in this model, it still provided insight into the importance of different environmental variables for mapping S. spinulosa biogenic reef habitat. Tidally induced mean bed shear stress was one of the most important predictor variables for both reef substrate and biogenic reef models, with ruggedness calculated at multiple scales from 3 m to 140 m also important for the reef substrate model. We identified previously unresolved relationships between temperate reef spatial distribution, hydrodynamic energy and seabed three-dimensional structure in energetic waters. Our findings contribute to a better understanding of the spatial ecology of high energy marine ecosystems and will inform evidence-based decision making for sustainable development, particularly within the growing tidal energy sector

Mortality risks associated with emergency admissions during weekends and public holidays: electronic health records study

Background: Higher mortality is associated with weekend hospital admission, but the contributions of varying illness severity and admission time to this ‘weekend effect’ remain unexplored. Methods: We analysed unselected emergency admissions to four Oxford University NHS hospitals, UK, January 2006-December 2014. The primary outcome was death within 30-days of admission (in/out of hospital), adjusted for multiple confounders in Cox models including or excluding test results. Findings: 257,596 individuals underwent 503,938 emergency admissions. 18,313 (4·8%) weekday and 6,070 (5·1%) weekend emergency admissions died within 30-days (p0.06). Interpretation: Adjusting for routine test results substantially reduced excess mortality associated with weekend/public holiday emergency admission. Adjusting for patient-level factors not available in our study could further reduce the residual excess mortality, which clustered around midday on Saturday/Sunday. Hospital workload was not associated with mortality. Together, these findings suggest that the ‘weekend effect’ arises from patient-level differences at admission rather than reduced hospital staffing or services