Hospital admissions for stroke and bleeding in Hounslow following a quality improvement initiative.

OBJECTIVE: Atrial fibrillation (AF) is the most common arrhythmia. Undiagnosed and poorly managed AF increases risk of stroke. The Hounslow AF quality improvement (QI) initiative was associated with improved quality of care for patients with AF through increased detection of AF and appropriate anticoagulation. This study aimed to evaluate whether there has been a change in stroke and bleeding rates in the Hounslow population following the QI initiative. METHODS: Using hospital admissions data from January 2011 to August 2018, interrupted time series analysis was performed to investigate the changes in standardised rates of admission with stroke and bleeding, following the start of the QI initiative in October 2014. RESULTS: There was a 17% decrease in the rate of admission with stroke as primary diagnosis (incidence rate ratio (IRR) 0.83; 95% CI 0.712 to 0.963; p<0.014). There was an even larger yet not statistically significant decrease in admission with stroke as primary diagnosis and AF as secondary diagnosis (IRR 0.75; 95% CI 0.550 to 1.025; p<0.071). No significant changes were observed in bleeding admissions. For each outcome, an additional regression model including both the level change and an interaction term for slope change was created. In all cases, the slope change was small and not statistically significant. CONCLUSION: Reduction in stroke admissions may be associated with the AF QI initiative. However, the immediate level change and non-significant slope change suggests a lack of effect of the intervention over time and that the decrease observed may be attributable to other events.

Effect of titanium dioxide nanoparticles on DNA methylation in multiple human cell lines.

Nanoscale titanium dioxide (TiO2) is manufactured in wide scale, with a range of applications in consumer products. Significant toxicity of TiO2 nanoparticles has, however, been recognized, suggesting considerable risk to human health. To evaluate fully their toxicity, assessment of the epigenetic action of these nanoparticles is critical. However, only few studies are available examining capability of nanoparticles to alter epigenetic integrity. In the present study, the effect of TiO2 nanoparticles exposure on DNA methylation, a major epigenetic mechanism, was investigated in in vitro cellular model systems. A panel of cells relevant to portals of human exposure (Caco-2 (colorectal), HepG2 (liver), NL20 (lung), and A-431 (skin)) was exposed to TiO2 nanoparticles to assess effects on global methylation, gene-specific methylation, and expression levels of DNA methyltransferases, MBD2, and UHRF1. Global methylation was determined by enzyme-linked immunosorbent assay-based immunochemical analysis. Degree of promoter methylation across a defined panel of genes was evaluated using EpiTect Methyl II Signature PCR System Array technology. Expression of DNMT1, DNMT3a, DNMT3b, MBD2, and URHF1 was quantified by qRT-PCR. Decrease in global DNA methylation in cell lines Caco-2, HepG2, and A-431 exposed to TiO2 nanoparticles was shown. Across four cell lines, eight genes (CDKN1A, DNAJC15, GADD45A, GDF15, INSIG1, SCARA3, TP53, and BNIP3) were identified in which promotors were methylated after exposure. Altered expression of these genes is associated with disease etiology. The results also revealed aberrant expression of epigenetic regulatory genes involved in DNA methylation (DNMT1, DNMT3a, DNMT3b, MBD2, and UHRF1) in TiO2 exposed cells, which was cell type dependent. Findings from this study clearly demonstrate the impact of TiO2 nanoparticles exposure on DNA methylation in multiple cell types, supporting potential involvement of this epigenetic mechanism in the toxicity of TiO2 nanoparticles. Hence for complete assessment of potential risk from nanoparticle exposure, epigenetic studies are critical.

Improving the quality of care for patients with or at risk of atrial fibrillation: an improvement initiative in UK general practices.

Objective: Atrial fibrillation (AF) is a growing problem internationally and a recognised cause of cardiovascular morbidity and mortality. The London borough of Hounslow has a lower than expected prevalence of AF, suggesting poor detection and associated undertreatment. To improve AF diagnosis and management, a quality improvement (QI) initiative was set up in 48 general practices in Hounslow. We aimed to study whether there was evidence of a change in AF diagnosis and management in Hounslow following implementation of interventions in this QI initiative. Methods: Using the general practice information system (SystmOne), data were retrospectively collected for 415 626 patients, who were actively registered at a Hounslow practice between 1 January 2011 and 31 August 2018. Process, outcome and balancing measures were analysed using statistical process control and interrupted time series regression methods. The baseline period was from 1 January 2011 to 30 September 2014 and the intervention period was from 1 October 2014 to 31 August 2018. Results: When comparing the baseline to the intervention period, (1) the rate of new AF diagnoses increased by 27% (relative risk 1.27; 95% CI 1.05 to 1.52; p<0.01); (2) ECG tests done for patients aged 60 and above increased; (3) CHA2DS2-VASc and HAS-BLED risk assessments within 30 days of AF diagnosis increased from 1.7% to 19% and 0.2% to 8.1%, respectively; (4) among those at higher risk of stroke, anticoagulation prescription within 30 days of AF diagnosis increased from 31% to 63% while prescription of antiplatelet monotherapy within the same time period decreased from 17% to 7.1%; and (5) average CHA2DS2-VASc and HAS-BLED risk scores did not change. Conclusion: Implementation of interventions in the Hounslow QI initiative coincided with improved AF diagnosis and management. Areas with perceived underdetection of AF should consider similar interventions and methodology.

Efficient red luminescence from organic-soluble Au25 clusters by ligand structure modification.

An efficient method to enhance visible luminescence in a visibly non-luminescent organic-soluble 4-(tert butyl)benzyl mercaptan (SBB)-stabilized Au25 cluster has been developed. This method relies mainly on enhancing the surface charge density on the cluster by creating an additional shell of thiolate on the cluster surface, which enhances visible luminescence. The viability of this method has been demonstrated by imparting red luminescence to various ligand-protected quantum clusters (QCs), observable to the naked eye. The bright red luminescent material derived from Au25SBB18 clusters was characterized using UV-vis and luminescence spectroscopy, TEM, SEM/EDS, XPS, TG, ESI and MALDI mass spectrometry, which collectively proposed an uncommon molecular formula of Au29SBB24S, suggested to be due to different stapler motifs protecting the Au25 core. The critical role of temperature on the emergence of luminescence in QCs has been studied. The restoration of the surface ligand shell on the Au25 cluster and subsequent physicochemical modification to the cluster were probed by various mass spectral and spectroscopic techniques. Our results provide fundamental insights into the ligand characteristics determining luminescence in QCs.

Supramolecular functionalization and concomitant enhancement in properties of Au(25) clusters.

We present a versatile approach for tuning the surface functionality of an atomically precise 25 atom gold cluster using specific host-guest interactions between ß-cyclodextrin (CD) and the ligand anchored on the cluster. The supramolecular interaction between the Au25 cluster protected by 4-(t-butyl)benzyl mercaptan, labeled Au25SBB18, and CD yielding Au25SBB18∩CDn (n = 1, 2, 3, and 4) has been probed experimentally using various spectroscopic techniques and was further analyzed by density functional theory calculations and molecular modeling. The viability of our method in modifying the properties of differently functionalized Au25 clusters is demonstrated. Besides modifying their optoelectronic properties, the CD moieties present on the cluster surface provide enhanced stability and optical responses which are crucial in view of the potential applications of these systems. Here, the CD molecules act as an umbrella which protects the fragile cluster core from the direct interaction with many destabilizing agents such as metal ions, ligands, and so on. Apart from the inherent biocompatibility of the CD-protected Au clusters, additional capabilities acquired by the supramolecular functionalization make such modified clusters preferred materials for applications, including those in biology.