Rosuvastatin for primary prevention in patients with European systematic coronary risk evaluation risk ≥5% or Framingham risk >20%: post hoc analyses of the JUPITER trial requested by European health authorities

Aims: On the basis of the JUPITER trial, European health authorities recently approved the use of rosuvastatin to reduce first major cardiovascular events among ‘high' global risk primary prevention patients defined either by Framingham risk score >20% or European systematic coronary risk evaluation (SCORE) ≥5%. However, as these are post hoc analyses, data describing these subgroups have not previously been available to the clinical community. Methods and results: We randomized 17 802 apparently healthy men aged ≥50 and women ≥60 with low-density lipoprotein cholesterol (LDL-C) 20% or SCORE risk ≥5%. During 1.8-year median follow-up (maximum 5 years) of patients with Framingham risk >20%, the rate of myocardial infarction/stroke/cardiovascular death was 9.4 and 18.2 per 1000 person-years in rosuvastatin and placebo-allocated patients, respectively [hazard ratio (HR): 0.50, 95% confidence interval (CI): 0.27–0.93, P = 0.028]. Among patients with SCORE risk ≥5%, the corresponding rates were 6.9 and 12.0 using a model extrapolating risk for age ≥65 years (HR: 0.57, 95% CI: 0.43–0.78, P = 0.0003) and rates were 5.9 and 12.7 when risk for age was capped at 65 years (HR: 0.47, 95% CI: 0.32–0.68, P 20% or SCORE risk ≥5%), but LDL-C levels not requiring pharmacologic treatment, rosuvastatin 20 mg significantly reduced major cardiovascular events. ClinicalTrial.gov Identifier: NCT0023968

Study of the influence of physical, chemical and biological conditions that influence the deterioration and protection of Underwater Cultural Heritage

Two wrecks related to the Battle of Trafalgar (1805) were studied. Following the guidelines of the UNESCO-2001 Convention for the Protection of the Underwater Cultural Heritage, a holistic and interdisciplinary approach based on the development of four of the thirty-six Rules of this international agreement was applied. A non-destructive survey technique was developed to obtain information from the scattered cannons and anchors without altering their condition (Rule 4). The work performed provided information about the origin of both wrecks, the Fougueux and the Bucentaure, two ships of the line of the French Navy, and allowed to characterize the state of conservation at each site without jeopardizing their future conservation in the marine environment. In addition, measurements of the main physical, chemical and biological variables allowed correlating the conservation status at each site with the marine environmental conditions (Rule 15). Thus, in Fougueux shipwreck large iron objects are corroding at a higher rate (between 0.180 and 0.246 mmpy) due to high sediment remobilization and transport induced by waves at this site, causing damage by direct mechanical effect on metallic material and by removing the layer of corrosion products developed on the artefacts. Meanwhile artillery on Bucentaure site, covered with thick layers of biological concretion, is well preserved, with lower corrosion rates (0.073 to 0.126 mmpy), and archaeological information is guaranteed. Finally, the effectiveness of the cathodic protection as a temporary measure for in situ conservation (Rule 1) was evaluated on a cannon. The use of a sacrificial anode after 9 months reduced the average corrosion rate (from 0.103 to 0.064 mmpy) and the percent of corrosion rate in 37.9%. These results are very useful for developing a decision making system of the Site Management Program, based on predictive models of artefacts permanence and risk factors in the marine environment (Rule 25)

The analytical framework of water and armed conflict: a focus on the 2006 Summer War between Israel and Lebanon

This paper develops an analytical framework to investigate the relationship between water and armed conflict, and applies it to the ‘Summer War’ of 2006 between Israel and Lebanon (Hezbollah). The framework broadens and deepens existing classifications by assessing the impact of acts of war as indiscriminate or targeted, and evaluating them in terms of international norms and law, in particular International Humanitarian Law (IHL). In the case at hand, the relationship is characterised by extensive damage in Lebanon to drinking water infrastructure and resources. This is seen as a clear violation of the letter and the spirit of IHL, while the partial destruction of more than 50 public water towers compromises water rights and national development goals. The absence of pre-war environmental baselines makes it difficult to gauge the impact on water resources, suggesting a role for those with first-hand knowledge of the hostilities to develop a more effective response before, during, and after armed conflict

Environmental impact assessments of the Three Gorges Project in China: issues and interventions

The paper takes China's authoritative Environmental Impact Statement for the Yangzi (Yangtze) Three Gorges Project (TGP) in 1992 as a benchmark against which to evaluate emerging major environmental outcomes since the initial impoundment of the Three Gorges reservoir in 2003. The paper particularly examines five crucial environmental aspects and associated causal factors. The five domains include human resettlement and the carrying capacity of local environments (especially land), water quality, reservoir sedimentation and downstream riverbed erosion, soil erosion, and seismic activity and geological hazards. Lessons from the environmental impact assessments of the TGP are: (1) hydro project planning needs to take place at a broader scale, and a strategic environmental assessment at a broader scale is necessary in advance of individual environmental impact assessments; (2) national policy and planning adjustments need to react quickly to the impact changes of large projects; (3) long-term environmental monitoring systems and joint operations with other large projects in the upstream areas of a river basin should be established, and the cross-impacts of climate change on projects and possible impacts of projects on regional or local climate considered. © 2013 Elsevier B.V.Xibao Xu, Yan Tan, Guishan Yan

Modulating an oxidative-inflammatory cascade: potential new treatment strategy for improving glucose metabolism, insulin resistance, and vascular function

Type 2 diabetes is a result of derangement of homeostatic systems of metabolic control and immune defense. Increases in visceral fat and organ adipose, environmental factors and genetic predisposition create imbalances of these homeostatic mechanisms, ultimately leading to a condition in which the oxidative environment cannot be held in check. A significant imbalance between the production of reactive oxygen species and antioxidant defenses, a condition called to oxidative stress, ensues, leading to alterations in stress-signalling pathways and potentially end-organ damage. Oxidative stress and metabolic inflammation upregulate the expression pro-inflammatory cytokines, including tissue necrosis factor alpha, monocyte chemoattractant protein-1 and interleukin-6, as well as activating stress-sensitive kinases, such as c-Jun N-terminal kinase (JNK), phosphokinase C isoforms, mitogen-activated protein kinase and inhibitor of kappa B kinase. The JNK pathway (specifically JNK-1) appears to be a regulator that triggers the oxidative-inflammation cascade that, if left unchecked, can become chronic and cause abnormal glucose metabolism. This can lead to insulin resistance and dysfunction of the vasculature and pancreatic β-cell. The series of events set in motion by the interaction between metabolic inflammation and oxidative stress constitutes an ‘oxidative-inflammatory cascade’, a delicate balance driven by mediators of the immune and metabolic systems, maintained through a positive feedback loop. Modulating an oxidative-inflammation cascade may improve glucose metabolism, insulin resistance and vascular function, thereby slowing the development and progression to cardiovascular diseases and type 2 diabetes

A randomized trial to assess the impact of opinion leader endorsed evidence summaries on the use of secondary prevention strategies in patients with coronary artery disease: the ESP-CAD trial protocol [NCT00175240]

BACKGROUND: Although numerous therapies have been shown to be beneficial in the prevention of myocardial infarction and/or death in patients with coronary disease, these therapies are under-used and this gap contributes to sub-optimal patient outcomes. To increase the uptake of proven efficacious therapies in patients with coronary disease, we designed a multifaceted quality improvement intervention employing patient-specific reminders delivered at the point-of-care, with one-page treatment guidelines endorsed by local opinion leaders ("Local Opinion Leader Statement"). This trial is designed to evaluate the impact of these Local Opinion Leader Statements on the practices of primary care physicians caring for patients with coronary disease. In order to isolate the effects of the messenger (the local opinion leader) from the message, we will also test an identical quality improvement intervention that is not signed by a local opinion leader ("Unsigned Evidence Statement") in this trial. METHODS: Randomized trial testing three different interventions in patients with coronary disease: (1) usual care versus (2) Local Opinion Leader Statement versus (3) Unsigned Evidence Statement. Patients diagnosed with coronary artery disease after cardiac catheterization (but without acute coronary syndromes) will be randomly allocated to one of the three interventions by cluster randomization (at the level of their primary care physician), if they are not on optimal statin therapy at baseline. The primary outcome is the proportion of patients demonstrating improvement in their statin management in the first six months post-catheterization. Secondary outcomes include examinations of the use of ACE inhibitors, anti-platelet agents, beta-blockers, non-statin lipid lowering drugs, and provision of smoking cessation advice in the first six months post-catheterization in the three treatment arms. Although randomization will be clustered at the level of the primary care physician, the design effect is anticipated to be negligible and the unit of analysis will be the patient. DISCUSSION: If either the Local Opinion Leader Statement or the Unsigned Evidence Statement improves secondary prevention in patients with coronary disease, they can be easily modified and applied in other communities and for other target conditions