An assessment of potential unintended consequences following a national antimicrobial stewardship programme in England: an interrupted time series analysis

Background: The 'Quality Premium' (QP) introduced in England in 2015 aimed to financially reward local healthcare commissioners for targeted reductions in primary care antibiotic prescribing. We aimed to evaluate possible unintended clinical outcomes related to this QP. Methods: Using Clinical Practice Research Datalink and Hospital Episode Statistics datasets, we examined general practitioner (GP) consultations (visits) and emergency hospital admissions related to a series of pre-defined conditions of unintended consequences of reduced prescribing. Monthly age and sex-standardised rates were calculated using a direct method of standardisation. We used segmented regression analysis of interrupted time series to evaluate the impact of the QP on seasonally adjusted outcome rates. Results: We identified 27,334 GP consultations and over five million emergency hospital admissions with pre-defined conditions. There was no evidence that the QP was associated with changes in GP consultation and hospital admission rates for the selected conditions combined. However, when each condition was considered separately, a significant increase in hospital admission rates was noted for quinsy, and significant decreases were seen for hospital-acquired pneumonia, scarlet fever, pyelonephritis and complicated urinary tract conditions. A significant decrease in GP consultation rates was estimated for empyema and scarlet fever. No significant changes were observed for other conditions. Conclusions: Findings from this study show that overall there was no significant association between the intervention and unintended clinical consequences, with the exception of a few specific conditions, most of which could be explained through other parallel policy changes or should be interpreted with caution due to small numbers

Age-related decline in antibiotic prescribing for uncomplicated respiratory tract infections in primary care in England following the introduction of a national financial incentive (the Quality Premium) for health commissioners to reduce use of antibiotics in the community: an interrupted time series analysis

Objectives: To assess the impact of the 2015/16 NHS England Quality Premium (which provided a financial incentive for Clinical Commissioning Groups to reduce antibiotic prescribing in primary care) on antibiotic prescribing by General Practitioners (GPs) for respiratory tract infections (RTIs). Method: Interrupted time series analysis using monthly patient-level consultation and prescribing data obtained from the Clinical Practice Research Datalink (CPRD), between April 2011 and March 2017. The study population comprised patients consulting a GP who were diagnosed with an RTI. We assessed the rate of antibiotic prescribing in patients (both aggregate and stratified by age) with a recorded diagnosis of uncomplicated RTI, before and after the implementation of the Quality Premium. Results: Prescribing rates decreased over the six year study period, with evident seasonality. Notably, there was a 3% drop in the rate of antibiotic prescribing (equating to 14.65 prescriptions per 1,000 RTI consultations) (p<0.05) in April 2015, coinciding with the introduction of the Quality Premium. This reduction was sustained, such that after two years there was a 3% decrease in prescribing relative to that expected had the pre-intervention trend continued. There was also a concurrent 2% relative reduction in the rate of broad-spectrum antibiotic prescribing. Antibiotic prescribing for RTIs diagnosed in children showed the greatest decline with a 6% relative change two years after the intervention. Of the RTI indications studied, the greatest reductions in antibiotic prescribing were seen for patients with sore throats. Conclusions: Community prescribing of antibiotics for RTIs significantly decreased following the introduction of the Quality Premium, with the greatest reduction seen in younger patients

Investigating Calcium-Mediated Arrhythmias via a Computational Model of a Rabbit Atrial Myocyte

The system of transverse and longitudinal sarcolemmal tubules (T-system) is observed to remodel in atrial fibrillation (AF) and heart failure (HF). The resulting calcium dysregulation has been suggested to underlie disruptions in excitation-contraction coupling, and increase the frequency of arrhythmic events at the cellular scale; however, these mechanisms and their importance are yet to be fully described. A stochastic, 3D, spatiotemporal model of the rabbit atrial myocyte was developed in order to study calcium-mediated arrhythmic phenomena at the cellular scale. Preliminary findings suggest a relationship between the severity of detubulation, and the promotion of spontaneous activity, and provides insight into the conditions required for the emergence of spontaneous activity within atrial myocytes in HF

Linearly polarized photoluminescence of InGaN quantum disks embedded in GaN nanorods

We have investigated the emission from InGaN/GaN quantum disks grown on the tip of GaN nanorods. The emission at 3.21 eV from the InGaN quantum disk doesn&apos;t show a Stark shift, and it is linearly polarized when excited perpendicular to the growth direction. The degree of linear polarization is about 39.3% due to the anisotropy of the nanostructures. In order to characterize a single nanostructure, the quantum disks were dispersed on a SiO2 substrate patterned with a metal reference grid. By rotating the excitation polarization angle from parallel to perpendicular relative to the nanorods, the variation of overall PL for the 3.21 eV peak was recorded and it clearly showed the degree of linear polarization (DLP) of 51.5%

Increased SERCA2a sub-cellular heterogeneity in right-ventricular heart failure inhibits excitation-contraction coupling and modulates arrhythmogenic dynamics

The intracellular calcium handling system of cardiomyocytes is responsible for controlling excitation-contraction coupling (ECC) and has been linked to pro-arrhythmogenic cellular phenomena in conditions such as heart failure (HF). SERCA2a, responsible for intracellular uptake, is a primary regulator of calcium homeostasis, and remodelling of its function has been proposed as a causal factor underlying cellular and tissue dysfunction in disease. Whereas adaptations to the global (i.e. whole-cell) expression of SERCA2a have been previously investigated in the context of multiple diseases, the role of its spatial profile in the sub-cellular volume has yet to be elucidated. We present an approach to characterize the sub-cellular heterogeneity of SERCA2a and apply this approach to quantify adaptations to the length-scale of heterogeneity (the distance over which expression is correlated) associated with right-ventricular (RV)-HF. These characterizations informed simulations to predict the functional implications of this heterogeneity, and its remodelling in disease, on ECC, the dynamics of calcium-transient alternans and the emergence of spontaneous triggered activity. Image analysis reveals that RV-HF is associated with an increase in length-scale and its inter-cellular variability; simulations predict that this increase in length-scale can reduce ECC and critically modulate the vulnerability to both alternans and triggered activity

Prospective mental imagery as its link with anxiety and depression in prisoners

Mental imagery is known to play a key role in the development and maintenance of depression and anxiety. Prisoners commonly experience psychological distress, but interventions to address this are currently lacking. We aimed to examine the link between prospective mental imagery and anxiety and depression among prisoners. One hundred twenty-three male prisoners from a Category C prison in southwest England participated in the study. They completed the Centre for Epidemiologic Studies Depression Scale (CES-D) and the General Anxiety Disorder Scale (GAD-7) to measure whether they experience depression and/or anxiety symptoms. Furthermore, they completed additional questionnaires to evaluate their prospective mental imagery. Results showed that 67.5% of prisoners presented with more depression symptoms and 27.7% with more anxiety symptoms. Supporting earlier findings, our data revealed that some dimensions of prospective mental imagery were significantly related with increased anxiety and depression symptoms in prisoners. Namely, intrusive negative personally relevant imagery was a positive predictor and likelihood of positive events a negative predictor of both anxiety and depression symptoms. The perceived likelihood of negative events was a positive predictor of depression. Intrusive verbal thought was a positive predictor of anxiety. The obtained results suggest the need to develop interventions not only targeting the reduction of prospective negative imagery but also the enhancement of positive mental imagery

Multiple reassortment events in the evolutionary history of H1N1 influenza A virus since 1918

The H1N1 subtype of influenza A virus has caused substantial morbidity and mortality in humans, first documented in the global pandemic of 1918 and continuing to the present day. Despite this disease burden, the evolutionary history of the A/H1N1 virus is not well understood, particularly whether there is a virological basis for several notable epidemics of unusual severity in the 1940s and 1950s. Using a data set of 71 representative complete genome sequences sampled between 1918 and 2006, we show that segmental reassortment has played an important role in the genomic evolution of A/H1N1 since 1918. Specifically, we demonstrate that an A/H1N1 isolate from the 1947 epidemic acquired novel PB2 and HA genes through intra-subtype reassortment, which may explain the abrupt antigenic evolution of this virus. Similarly, the 1951 influenza epidemic may also have been associated with reassortant A/H1N1 viruses. Intra-subtype reassortment therefore appears to be a more important process in the evolution and epidemiology of H1N1 influenza A virus than previously realized

Physical activity and breast cancer survival

Physical activity improves quality of life after a breast cancer diagnosis, and a beneficial effect on survival would be particularly welcome. Four observational studies have now reported decreased total mortality among physically active women with breast cancer; the two largest have also reported decreased breast cancer specific mortality. The estrogen pathway and the insulin pathway are two potential mechanisms by which physical activity could affect breast cancer survival. Randomized trials are ongoing but trials of lifestyle factors are notoriously challenging to perform. Women with breast cancer have little to lose and may possibly gain from moderate exercise

Incoherent non-Fermi liquid scattering in a Kondo lattice

One of the most notorious non-Fermi liquid properties of both archetypal heavy-fermion systems [1-4] and the high-Tc copper oxide superconductors [5] is an electrical resistivity that evolves linearly with temperature, T. In the heavy-fermion superconductor CeCoIn5 [5], this linear behaviour was one of the first indications of the presence of a zero-temperature instability, or quantum critical point. Here, we report the observation of a unique control parameter of T-linear scattering in CeCoIn5, found through systematic chemical substitutions of both magnetic and non-magnetic rare-earth, R, ions into the Ce sub-lattice. We find that the evolution of inelastic scattering in Ce1-xRxCoIn5 is strongly dependent on the f-electron configuration of the R ion, whereas two other key properties -- Cooper-pair breaking and Kondo-lattice coherence -- are not. Thus, T-linear resistivity in CeCoIn5 is intimately related to the nature of incoherent scattering centers in the Kondo lattice, which provides insight into the anomalous scattering rate synonymous with quantum criticality [7].Comment: 4 pages, 3 figures (published version

Strange Attractors in Dissipative Nambu Mechanics : Classical and Quantum Aspects

We extend the framework of Nambu-Hamiltonian Mechanics to include dissipation in $R^{3}$ phase space. We demonstrate that it accommodates the phase space dynamics of low dimensional dissipative systems such as the much studied Lorenz and R\"{o}ssler Strange attractors, as well as the more recent constructions of Chen and Leipnik-Newton. The rotational, volume preserving part of the flow preserves in time a family of two intersecting surfaces, the so called {\em Nambu Hamiltonians}. They foliate the entire phase space and are, in turn, deformed in time by Dissipation which represents their irrotational part of the flow. It is given by the gradient of a scalar function and is responsible for the emergence of the Strange Attractors. Based on our recent work on Quantum Nambu Mechanics, we provide an explicit quantization of the Lorenz attractor through the introduction of Non-commutative phase space coordinates as Hermitian $N \times N$ matrices in $R^{3}$. They satisfy the commutation relations induced by one of the two Nambu Hamiltonians, the second one generating a unique time evolution. Dissipation is incorporated quantum mechanically in a self-consistent way having the correct classical limit without the introduction of external degrees of freedom. Due to its volume phase space contraction it violates the quantum commutation relations. We demonstrate that the Heisenberg-Nambu evolution equations for the Quantum Lorenz system give rise to an attracting ellipsoid in the $3 N^{2}$ dimensional phase space.Comment: 35 pages, 4 figures, LaTe