Determining propensity for sub-optimal low-density lipoprotein cholesterol response to statins and future risk of cardiovascular disease

Background: Variability in low-density lipoprotein cholesterol (LDL-C) response to statins is underappreciated. We characterised patients by their statin response (SR), baseline risk of cardiovascular disease (CVD) and 10-year CVD outcomes. / Methods and results: A multivariable model was developed using 183,213 United Kingdom (UK) patients without CVD to predict probability of sub-optimal SR, defined by guidelines as <40% reduction in LDL-C. We externally validated the model in a Hong Kong (HK) cohort (n = 170,904). Patients were stratified into four groups by predicted SR and 10-year CVD risk score: [SR1] optimal SR & low risk; [SR2] sub-optimal SR & low risk; [SR3] optimal SR & high risk; [SR4] sub-optimal SR & high risk; and 10-year hazard ratios (HR) determined for first major adverse cardiovascular event (MACE). Our SR model included 12 characteristics, with an area under the curve of 0.70 (95% confidence interval [CI] 0.70–0.71; UK) and 0.68 (95% CI 0.67–0.68; HK). HRs for MACE in predicted sub-optimal SR with low CVD risk groups (SR2 to SR1) were 1.39 (95% CI 1.35–1.43, p<0.001; UK) and 1.14 (95% CI 1.11–1.17, p<0.001; HK). In both cohorts, patients with predicted sub-optimal SR with high CVD risk (SR4 to SR3) had elevated risk of MACE (UK HR 1.36, 95% CI 1.32–1.40, p<0.001: HK HR 1.25, 95% CI 1.21–1.28, p<0.001). / Conclusions: Patients with sub-optimal response to statins experienced significantly more MACE, regardless of baseline CVD risk. To enhance cholesterol management for primary prevention, statin response should be considered alongside risk assessment

Lipid levels and major adverse cardiovascular events in patients initiated on statins for primary prevention: an international population-based cohort study protocol

Background : Clinical guidelines recommend specific targets for low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) for primary prevention of cardiovascular disease (CVD). Furthermore, individual variability in lipid response to statin therapy requires assessment of the association in diverse populations. Aim: To assess whether lower concentrations of LDL-C and non-HDL-C are associated with a reduced risk of major adverse cardiovascular events (MACE) in primary prevention of CVD. Design & setting: An international, new-user, cohort study will be undertaken. It will use data from three electronic health record databases from three global regions: Clinical Practice Research Datalink, UK; PREDICT-CVD, New Zealand (NZ); and the Clinical Data and Analysis Reporting System, Hong Kong (HK). Method: New statin users without a history of atherosclerotic CVD, heart failure, or chronic kidney disease, with baseline and follow-up lipid levels will be eligible for inclusion. Patients will be classified according to LDL-C (<1.4, 1.4–1.7, 1.8–2.5, and ≥2.6 mmol/l) and non-HDL-C (<2.2, 2.2–2.5, 2.6–3.3, and ≥3.4 mmol/l) concentrations 24 months after initiating statin therapy. The primary outcome of interest is MACE, defined as the first occurrence of coronary heart disease, stroke, or cardiovascular death. Secondary outcomes include all-cause mortality and the individual components of MACE. Sensitivity analyses will be conducted using lipid levels at 3 and 12 months after starting statin therapy. Conclusion: Results will inform clinicians about the benefits of achieving guideline recommended concentrations of LDL-C for primary prevention of CVD

Monitoring bridge degradation using dynamic strain, acoustic emission and environmental data

This paper studies the long term structural behaviour of a Victorian railway viaduct under train loading and temperature variation. A multi-sensing, self-sustaining and remotely controlled data acquisition system combines fibre Bragg grating strain sensors with acoustic emission sensors for the study of both global dynamic deformation and local masonry deterioration. A statistical analysis of fibre Bragg grating signals reveals regions with permanent change in the dynamic deformation of the bridge over the last two years, whereas in other locations the deformation follows a seasonal cyclic pattern. In order to decouple changes in structural behaviour due to real mechanical damage from normal seasonal effect, the paper studies the ambient temperature effect on the dynamic deformation of the bridge, showing a clear linear dependence. In particular, when temperature increases, the dynamic strain due to train loading decreases uniformly in the longitudinal direction. In the transverse direction, where the thermal expansion is not constrained, the decrease is smaller. Decoupling damage from normal seasonal effect is of critical importance for the development of reliable early warning structural alert systems for infrastructure networks. The paper further studies local masonry deterioration at four critical location by combining data from the two sensing technologies: fibre optic and acoustic emission sensors.This work is being funded by the Lloyd’s Register Foundation, EPSRC and Innovate UK through the Data-Centric Engineering programme of the Alan Turing Institute and through the Cambridge Centre for Smart Infrastructure and Construction. Funding for the monitoring installation was provided by EPSRC under the Ref. EP/N021614/1 grant and by Innovate UK under the Ref. 920035 grant

Diversity of floral visitors to sympatric Lithophragma species differing in floral morphology

Most coevolving relationships between pairs of species are embedded in a broader multispecific interaction network. The mutualistic interaction between Lithophragma parviflorum (Saxifragaceae) and its pollinating floral parasite Greya politella (Lepidoptera, Prodoxidae) occurs in some communities as a pairwise set apart from most other interactions in those communities. In other communities, however, this pair of species occurs with congeners and with other floral visitors to Lithophragma. We analyzed local and geographic differences in the network formed by interactions between Lithophragma plants and Greya moths in communities containing two Lithophragma species, two Greya species, and floral visitors other than Greya that visit Lithophragma flowers. Our goal was to evaluate if non-Greya visitors were common, if visitor assembly differs between Lithophragma species and populations and if these visitors act as effective pollinators. Sympatric populations of L. heterophyllum and L. parviflorum differ in floral traits that may affect assemblies of floral visitors. Visitation rates by non-Greya floral visitors were low, and the asymptotic number of visitor species was less than 20 species in all populations. Lithophragma species shared some of the visitors, with visitor assemblages differing between sites more for L. heterophyllum than for L. parviflorum. Pollination efficacy experiments showed that most visitors were poor pollinators. Single visits to flowers by this assemblage of species resulted in significantly higher seed set in Lithophragma heterophyllum (30.6 ± 3.9 SE) than in L. parviflorum (4.7 ± 3.4 SE). This difference was consistent between sites, suggesting that these visitors provide a better fit to the floral morphology of L. heterophyllum. Overall, none of the non-Greya visitors appears to be either sufficiently common or efficient as a pollinator to impose strong selection on any of these four Lithophragma populations in comparison with Greya, which occurs within almost all populations of these species throughout their geographic ranges

Investigation of the Hemodynamic Effect of Stent Wires on Renal Arteries in Patients with Abdominal Aortic Aneurysms Treated with Suprarenal Stent-Grafts

The purpose of the study was to investigate the hemodynamic effect of stent struts (wires) on renal arteries in patients with abdominal aortic aneurysms (AAAs) treated with suprarenal stent-grafts. Two sample patients with AAA undergoing multislice CT angiography pre- and postsuprarenal fixation of stent-grafts were selected for inclusion in the study. Eight juxtarenal models focusing on the renal arteries were generated from the multislice CT datasets. Four types of configurations of stent wires crossing the renal artery ostium were simulated in the segmented aorta models: a single wire crossing centrally, a single wire crossing peripherally, a V-shaped wire crossing centrally, and multiple wires crossing peripherally. The blood flow pattern, flow velocity, wall pressure, and wall shear stress at the renal arteries pre- and post-stent-grafting were analyzed and compared using a two-way fluid structure interaction analysis. The stent wire thickness was simulated with a diameter of 0.4, 1.0, and 2.0 mm, and hemodynamic analysis was performed at different cardiac cycles. The interference of stent wires with renal blood flow was mainly determined by the thickness of stent wires and the type of configuration of stent wires crossing the renal ostium. The flow velocity was reduced by 20–30% in most of the situations when the stent wire thickness increased to 1.0 and 2.0 mm. Of the four types of configuration, the single wire crossing centrally resulted in the highest reduction of flow velocity, ranging from 21% to 28.9% among three different wire thicknesses. Wall shear stress was also dependent on the wire thickness, which decreased significantly when the wire thickness reached 1.0 and 2.0 mm. In conclusion, our preliminary study showed that the hemodynamic effect of suprarenal stent wires in patients with AAA treated with suprarenal stent-grafts was determined by the thickness of suprarenal stent wires. Research findings in our study are useful for follow-up of patients treated with suprarenal stent-grafts to ensure long-term safety of the suprarenal fixation

Monitoring of risk perceptions and correlates of precautionary behaviour related to human avian influenza during 2006 - 2007 in the Netherlands: results of seven consecutive surveys

BACKGROUND: Avian influenza (AI) is a public health challenge because of ongoing spread and pandemic potential. Non-pharmaceutical measures are important to prevent the spread of AI and to contain a pandemic. The effectiveness of such measures is largely dependent on the behaviour of the population. Risk perception is a central element in changing behaviour. This study aimed to investigate perceived vulnerability, severity and precautionary behaviour related to AI in the Netherlands during seven consecutive surveys in 2006 - 2007 as well as possible trends in risk perception and self-reported precautionary behaviours. METHODS: Seven web-based surveys were conducted including 3,840 respondents over a one-year period. Time trends were analyzed with linear regression analyses. Multivariate analysis was used to study determinants of precautionary behaviour. RESULTS: While infection with AI was considered a very severe health problem with mean score of 4.57 (scale 1 - 5); perceived vulnerability was much lower, with a mean score of 1.69. While perceived severity remained high, perceived vulnerability decreased slightly during a one-year period covering part of 2006 and 2007. Almost half of the respondents (46%) reported taking one or more preventive measures, with 36% reporting to have stayed away from (wild) birds or poultry. In multivariate logistic regression analysis the following factors were significantly associated with taking preventive measures: time of the survey, higher age, lower level of education, non-Dutch ethnicity, vaccinated against influenza, higher perceived severity, higher perceived vulnerability, higher self efficacy, lower level of knowledge, more information about AI, and thinking more about AI. Self efficacy was a stronger predictor of precautionary behaviour for those who never or seldom think about AI (OR 2.3, 95% CI 1.9 - 2.7), compared to those who think about AI more often (OR 1.5, 95% CI 1.2 - 1.9). CONCLUSIONS: The fact that perceived severity of AI appears to be high and remains so over time offers a good point of departure for more specific risk communications to promote precautionary actions. Such communications should aim at improving knowledge about the disease and preventive actions, and focus on perceived personal vulnerability and self efficacy in taking preventive measures

Benefits and risks of the hormetic effects of dietary isothiocyanates on cancer prevention

The isothiocyanate (ITC) sulforaphane (SFN) was shown at low levels (1-5 µM) to promote cell proliferation to 120-143% of the controls in a number of human cell lines, whilst at high levels (10-40 µM) it inhibited such cell proliferation. Similar dose responses were observed for cell migration, i.e. SFN at 2.5 µM increased cell migration in bladder cancer T24 cells to 128% whilst high levels inhibited cell migration. This hormetic action was also found in an angiogenesis assay where SFN at 2.5 µM promoted endothelial tube formation (118% of the control), whereas at 10-20 µM it caused significant inhibition. The precise mechanism by which SFN influences promotion of cell growth and migration is not known, but probably involves activation of autophagy since an autophagy inhibitor, 3-methyladenine, abolished the effect of SFN on cell migration. Moreover, low doses of SFN offered a protective effect against free-radical mediated cell death, an effect that was enhanced by co-treatment with selenium. These results suggest that SFN may either prevent or promote tumour cell growth depending on the dose and the nature of the target cells. In normal cells, the promotion of cell growth may be of benefit, but in transformed or cancer cells it may be an undesirable risk factor. In summary, ITCs have a biphasic effect on cell growth and migration. The benefits and risks of ITCs are not only determined by the doses, but are affected by interactions with Se and the measured endpoint

Protocol for a randomised controlled trial examining the impact of a web-based personally controlled health management system on the uptake of influenza vaccination rates

<p>Abstract</p> <p>Background</p> <p>Online social networking and personally controlled health management systems (PCHMS) offer a new opportunity for developing innovative interventions to prevent diseases of public health concern (e.g., influenza) but there are few comparative studies about patterns of use and impact of these systems.</p> <p>Methods/Design</p> <p>A 2010 CONSORT-compliant randomised controlled trial with a two-group parallel design will assess the efficacy of a web-based PCHMS called <it>Healthy.me </it>in facilitating the uptake of influenza vaccine amongst university students and staff. Eligible participants are randomised either to obtain access to <it>Healthy.me </it>or a 6-month waitlist. Participants complete pre-study, post-study and monthly surveys about their health and utilisation of health services. A post-study clinical audit will be conducted to validate self-reports about influenza vaccination and visits to the university health service due to influenza-like illness (ILI) amongst a subset of participants. 600 participants older than 18 years with monthly access to the Internet and email will be recruited. Participants who (i) discontinue the online registration process; (ii) report obtaining an influenza vaccination in 2010 before the commencement of the study; or (iii) report being influenced by other participants to undertake influenza vaccination will be excluded from analysis. The primary outcome measure is the number of participants obtaining influenza vaccination during the study. Secondary outcome measures include: number of participants (i) experiencing ILI symptoms, (ii) absent from or experiencing impairment in work or study due to ILI symptoms, (iii) using health services or medications due to ILI symptoms; (iv) expressing positive or negative attitudes or experiences towards influenza vaccination, via their reasons of receiving (or not receiving) influenza vaccine; and (v) their patterns of usage of <it>Healthy.me </it>(e.g., frequency and timing of hits, duration of access, uptake of specific functions).</p> <p>Discussion</p> <p>This study will provide new insights about the utility of online social networking and PCHMS for public health and health promotion. It will help to assess whether a web-based PCHMS, with connectivity to a health service provider, containing information and self-management tools, can improve the uptake of preventive health services amongst university students and staff.</p> <p>Trial registration</p> <p><a href="http://www.anzctr.org.au/ACTRN12610000386033.aspx">ACTRN12610000386033</a> (Australian New Zealand Clinical Trials Registry)</p