Showing papers by "Ben S. Cooper published in 2012"

Evaluation of the national Cleanyourhands campaign to reduce Staphylococcus aureus bacteraemia and Clostridium difficile infection in hospitals in England and Wales by improved hand hygiene: four year, prospective, ecological, interrupted time series study

Abstract: Objective To evaluate the impact of the Cleanyourhands campaign on rates of hospital procurement of alcohol hand rub and soap, report trends in selected healthcare associated infections, and investigate the association between infections and procurement.

Fool's Gold: Why Imperfect Reference Tests Are Undermining the Evaluation of Novel Diagnostics: A Reevaluation of 5 Diagnostic Tests for Leptospirosis

Abstract: Background. We observed that some patients with clinical leptospirosis supported by positive results of rapid tests were negative for leptospirosis on the basis of our diagnostic gold standard, which involves isolation of Leptospira species from blood culture and/or a positive result of a microscopic agglutination test (MAT). We hypothesized that our reference standard was imperfect and used statistical modeling to investigate this hypothesis. Methods. Data for 1652 patients with suspected leptospirosis recruited during three observational studies and one randomized control trial that described the application of culture, MAT, immunofluorescence assay (IFA), lateral flow (LF) and/or PCR targeting the 16S rRNA gene were reevaluated using Bayesian latent class models and random-effects meta-analysis. Results. The estimated sensitivities of culture alone, MAT alone, and culture plus MAT (for which the result was considered positive if one or both tests had a positive result) were 10.5% (95% credible interval [CrI], 2.7%–27.5%), 49.8% (95% CrI, 37.6%–60.8%), and 55.5% (95% CrI, 42.9%–67.7%), respectively. These low sensitivities were present across all 4 studies. The estimated specificity of MAT alone (and of culture plus MAT) was 98.8% (95% CrI, 92.8%–100.0%). The estimated sensitivities and specificities of PCR (52.7% [95% CrI, 45.2%– 60.6%] and 97.2% [95% CrI, 92.0%–99.8%], respectively), lateral flow test (85.6% [95% CrI, 77.5%–93.2%] and 96.2% [95% CrI, 87.7%–99.8%], respectively), and immunofluorescence assay (45.5% [95% CrI, 33.3%–60.9%] and 96.8% [95% CrI, 92.8%–99.8%], respectively) were considerably different from estimates in which culture plus MAT was considered a perfect gold standard test. Conclusions. Our findings show that culture plus MAT is an imperfect gold standard against which to compare alterative tests for the diagnosis of leptospirosis. Rapid point-of-care tests for this infection would bring an important improvement in patient care, but their future evaluation will require careful consideration of the reference test(s) used and the inclusion of appropriate statistical models.

The Feedback Intervention Trial (FIT) — Improving Hand-Hygiene Compliance in UK Healthcare Workers: A Stepped Wedge Cluster Randomised Controlled Trial

Abstract: Introduction: Achieving a sustained improvement in hand-hygiene compliance is the WHO’s first global patient safety challenge. There is no RCT evidence showing how to do this. Systematic reviews suggest feedback is most effective and call for long term well designed RCTs, applying behavioural theory to intervention design to optimise effectiveness. Methods: Three year stepped wedge cluster RCT of a feedback intervention testing hypothesis that the intervention was more effective than routine practice in 16 English/Welsh Hospitals (16 Intensive Therapy Units [ITU]; 44 Acute Care of the Elderly [ACE] wards) routinely implementing a national cleanyourhands campaign). Intervention-based on Goal & Control theories. Repeating 4 week cycle (20 mins/week) of observation, feedback and personalised action planning, recorded on forms. Computer-generated stepwise entry of all hospitals to intervention. Hospitals aware only of own allocation. Primary outcome: direct blinded hand hygiene compliance (%). Results: All 16 trusts (60 wards) randomised, 33 wards implemented intervention (11 ITU, 22 ACE). Mixed effects regression analysis (all wards) accounting for confounders, temporal trends, ward type and fidelity to intervention (forms/month used). Intention to Treat Analysis: Estimated odds ratio (OR) for hand hygiene compliance rose post randomisation (1.44; 95% CI 1.18, 1.76;p,0.001) in ITUs but not ACE wards, equivalent to 7–9% absolute increase in compliance. Per-Protocol Analysis for Implementing Wards: OR for compliance rose for both ACE (1.67 [1.28–2.22]; p,0.001) & ITUs (2.09 [1.55–2.81];p,0.001) equating to absolute increases of 10–13% and 13–18% respectively. Fidelity to intervention closely related to compliance on ITUs (OR 1.12 [1.04, 1.20];p=0.003 per completed form) but not ACE wards. Conclusion: Despite difficulties in implementation, intention-to-treat, per-protocol and fidelity to intervention, analyses showed an intervention coupling feedback to personalised action planning produced moderate but significant sustained improvements in hand-hygiene compliance, in wards implementing a national hand-hygiene campaign. Further implementation studies are needed to maximise the intervention’s effect in different settings.

Search for a heavy top-quark partner in final states with two leptons with the ATLAS detector at the LHC

Abstract: The results of a search for direct pair production of heavy top-quark partners in 4.7 fb−1 of integrated luminosity from pp collisions at s√=7 TeV collected by the ATLAS detector at the LHC are reported. Heavy top-quark partners decaying into a top quark and a neutral non-interacting particle are searched for in events with two leptons in the final state. No excess above the Standard Model expectation is observed. Limits are placed on the mass of a supersymmetric scalar top and of a spin-1/2 top-quark partner. A spin-1/2 top-quark partner with a mass between 300 GeV and 480 GeV, decaying to a top quark and a neutral non-interacting particle lighter than 100 GeV, is excluded at 95% confidence level.

Rapidity gap cross sections measured with the ATLAS detector in pp collisions at √ s =7 TeV

Abstract: Pseudorapidity gap distributions in proton-proton collisions at root s = 7 TeV are studied using a minimum bias data sample with an integrated luminosity of 7.1 mu b(-1). Cross sections are measured differentially in terms of Delta eta(F), the larger of the pseudorapidity regions extending to the limits of the ATLAS sensitivity, at eta = +/- 4.9, in which no final state particles are produced above a transverse momentum threshold p(T)(cut). The measurements span the region 0 Xp), enhanced by double dissociation (pp -> XY) where the invariant mass of the lighter of the two dissociation systems satisfies M-Y less than or similar to 7 GeV. The resulting cross section is ds sigma/d Delta eta(F) approximate to 1 mb for Delta eta(F) greater than or similar to 3. The large rapidity gap data are used to constrain the value of the Pomeron intercept appropriate to triple Regge models of soft diffraction. The cross section integrated over all gap sizes is compared with other LHC inelastic cross section measurements.

An Association Between Bacterial Genotype Combined With a High-Vancomycin Minimum Inhibitory Concentration and Risk of Endocarditis in Methicillin-Resistant Staphylococcus aureus Bloodstream Infection

Abstract: Vancomycin is first-line therapy for healthcare-associated methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSIs) in many countries. It is therefore of concern that some studies have reported increases in MRSA vancomycin minimum inhibitory concentrations (V-MICs) within the susceptible range (≤2 μg/mL) [1, 2], a phenomenon called “MIC creep.” However, this has not been evident in other studies [3, 4], and it remains unclear whether observed increases represent replacement by intrinsically more resistant clones [5] or an increase in the population V-MIC profile within clones [5]. Concerns about V-MIC creep are compounded by reports that bloodstream and other infections caused by MRSA isolates with high V-MICs (1.5–2 μg/mL) are associated with a worse outcome [6–8], which may be only in part explained by vancomycin treatment parameters and the V-MIC. For example, high V-MIC isolates have been associated with less shock [8], a lower inflammatory response [9], and lower pathogenicity in a Galleria mellonella infection model [10]; however, this would suggest lower mortality for high V-MIC isolates, which has indeed been observed in one study [11]. These reports might be explained by low V-MIC strains having an inflammation-inducing phenotype causing acute sepsis, and high V-MIC strains having cell wall changes leading to persistence and immune evasion [9, 12]. Such a proposal is consistent with data emerging from genotypic and phenotypic analysis of MRSA strains with reduced vancomycin susceptibility [13]. Another important consideration is bacterial genotype, which has been linked with differences in population V-MIC profile and clinically significant events such as bacteremia, persistent bacteremia, or the ability to cause hematogenous complications [14–16]. Thus, differences in V-MIC and genotype may both affect disease pathogenesis and clinical outcomes. The aims of this study were 2-fold: to determine whether vancomycin creep has occurred in a large genotyped collection of MRSA bloodstream isolates from a single center and to test the hypothesis that strains with a high V-MIC are associated with an increased rate of hematogenous complications.

Quantifying type-specific reproduction numbers for nosocomial pathogens: evidence for heightened transmission of an Asian sequence type 239 MRSA clone.

Abstract: An important determinant of a pathogen's success is the rate at which it is transmitted from infected to susceptible hosts. Although there are anecdotal reports that methicillin-resistant Staphylococcus aureus (MRSA) clones vary in their transmissibility in hospital settings, attempts to quantify such variation are lacking for common subtypes, as are methods for addressing this question using routinely-collected MRSA screening data in endemic settings. Here we present a method to quantify the time-varying transmissibility of different subtypes of common bacterial nosocomial pathogens using routine surveillance data. The method adapts approaches for estimating reproduction numbers based on the probabilistic reconstruction of epidemic trees, but uses relative hazards rather than serial intervals to assign probabilities to different sources for observed transmission events. The method is applied to data collected as part of a retrospective observational study of a concurrent MRSA outbreak in the United Kingdom with dominant endemic MRSA clones (ST22 and ST36) and an Asian ST239 MRSA strain (ST239-TW) in two linked adult intensive care units, and compared with an approach based on a fully parametric transmission model. The results provide support for the hypothesis that the clones responded differently to an infection control measure based on the use of topical antiseptics, which was more effective at reducing transmission of endemic clones. They also suggest that in one of the two ICUs patients colonized or infected with the ST239-TW MRSA clone had consistently higher risks of transmitting MRSA to patients free of MRSA. These findings represent some of the first quantitative evidence of enhanced transmissibility of a pandemic MRSA lineage, and highlight the potential value of tailoring hospital infection control measures to specific pathogen subtypes.

Pandemic influenza H1N1 2009 in Thailand.

Abstract: Background: Developing a quantitative understanding of pandemic influenza dynamics in South-East Asia is important for informing future pandemic planning Hence, transmission dynamics of influenza A/H1N1 were determined across space and time in Thailand Methods: Dates of symptom onset were obtained for all daily laboratory-confirmed cases of influenza A/H1N1pdm in Thailand from 3 May 2009 to 26 December 2010 for four different geographic regions (Central, North, North-East, and South) These data were analysed using a probabilistic epidemic reconstruction, and estimates of the effective reproduction number, R(t), were derived by region and over time Results: Estimated R(t) values for the first wave peaked at 154 (95% CI: 142-171) in the Central region and 164 (95% CI: 138-192) in the North, whilst the corresponding values in the North-East and the South were 130 (95% CI: 117-146) and 139 (95% CI: 132-145) respectively As the R(t) in the Central region fell below one, the value of R(t) in the rest of Thailand increased above one R(t) was above one for 30 days continuously through the first wave in all regions of Thailand During the second wave R(t) was only marginally above one in all regions except the South Conclusions: In Thailand, the value of R(t) varied by region in the two pandemic waves Higher R(t) estimates were found in Central and Northern regions in the first wave Knowledge of regional variation in transmission potential is needed for predicting the course of future pandemics and for analysing the potential impact of control measures