NITRATE-CIN Study: Protocol of a Randomized (1:1) Single-Center, UK, Double-Blind Placebo-Controlled Trial Testing the Effect of Inorganic Nitrate on Contrast-Induced Nephropathy in Patients Undergoing Coronary Angiography for Acute Coronary Syndromes.

BACKGROUND: Contrast-induced nephropathy (CIN), an acute kidney injury resulting from the administration of intravascular iodinated contrast media, is a significant cause of morbidity/mortality following coronary angiographic procedures in high-risk patients. Despite preventative measures intended to mitigate the risk of CIN, there remains a need for novel effective treatments. Evidence suggests that delivery of nitric oxide (NO) through chemical reduction of inorganic nitrate to NO may offer a novel therapeutic strategy to reduce CIN and thus preserve long term renal function. DESIGN: The NITRATE-CIN trial is a single-center, randomized, double-blind placebo-controlled trial, which plans to recruit 640 patients presenting with acute coronary syndromes (ACS) who are at risk of CIN. Patients will be randomized to either inorganic nitrate therapy (capsules containing 12 mmol KNO3) or placebo capsules containing potassium chloride (KCl) daily for 5 days. The primary endpoint is development of CIN using the Kidney Disease Improving Global Outcomes (KDIGO) criteria. A key secondary endpoint is renal function over a 3-month follow-up period. Additional secondary endpoints include serum renal biomarkers (e.g. neutrophil gelatinase-associated lipocalin) at 6 h, 48 h and 3 months following administration of contrast. Cost-effectiveness of inorganic nitrate therapy will also be evaluated. SUMMARY: This study is designed to investigate the hypothesis that inorganic nitrate treatment decreases the rate of CIN as part of semi-emergent coronary angiography for ACS. Inorganic nitrate is a simple and easy to administer intervention that may prove useful in prevention of CIN in at-risk patients undergoing coronary angiographic procedures.

Harmful Compounds and Willingness to Buy for Reduced-Additives Salami. An Outlook on Italian Consumers.

The consumption pattern of salami has been subjected to relatively widespread attention by academician, but few studies concerning the health implications of salami consumption have been published. Since additives and product origins represent important attributes for salami, the objective of this paper is twofold: (i) to explore the role of two additives, salt and nitrates, in addition to the Italian origin, in relation to consumer attitudes and preferences towards salami, (ii) to segment consumer behaviour by assessing their willingness-to-buy salami, in order to verify whether different purchasing patterns can be identified within the different social groups. The analysis was conducted on two different levels. The first was developed through a conjoint analysis, while the second implemented a frequency analysis based on a bivariate analysis. Results show the price as one of the most important variables in identifying the quality level of salami, in addition, certain socio-economic segments of consumers show a significant propensity to pay an additional price for salami with a low salt content and is nitrate-free.

Flexible NO(x) abatement from power plants in the eastern United States.

Emission controls that provide incentives for maximizing reductions in emissions of ozone precursors on days when ozone concentrations are highest have the potential to be cost-effective ozone management strategies. Conventional prescriptive emissions controls or cap-and-trade programs consider all emissions similarly regardless of when they occur, despite the fact that contributions to ozone formation may vary. In contrast, a time-differentiated approach targets emissions reductions on forecasted high ozone days without imposition of additional costs on lower ozone days. This work examines simulations of such dynamic air quality management strategies for NO(x) emissions from electric generating units. Results from a model of day-specific NO(x) pricing applied to the Pennsylvania-New Jersey-Maryland (PJM) portion of the northeastern U.S. electrical grid demonstrate (i) that sufficient flexibility in electricity generation is available to allow power production to be switched from high to low NO(x) emitting facilities, (ii) that the emission price required to induce EGUs to change their strategies for power generation are competitive with other control costs, (iii) that dispatching strategies, which can change the spatial and temporal distribution of emissions, lead to ozone concentration reductions comparable to other control technologies, and (iv) that air quality forecasting is sufficiently accurate to allow EGUs to adapt their power generation strategies.

Estimation of incidence and social cost of colon cancer due to nitrate in drinking water in the EU: a tentative cost-benefit assessment.

BACKGROUND: Presently, health costs associated with nitrate in drinking water are uncertain and not quantified. This limits proper evaluation of current policies and measures for solving or preventing nitrate pollution of drinking water resources. The cost for society associated with nitrate is also relevant for integrated assessment of EU nitrogen policies taking a perspective of welfare optimization. The overarching question is at which nitrogen mitigation level the social cost of measures, including their consequence for availability of food and energy, matches the social benefit of these measures for human health and biodiversity. METHODS: Epidemiological studies suggest colon cancer to be possibly associated with nitrate in drinking water. In this study risk increase for colon cancer is based on a case-control study for Iowa, which is extrapolated to assess the social cost for 11 EU member states by using data on cancer incidence, nitrogen leaching and drinking water supply in the EU. Health costs are provisionally compared with nitrate mitigation costs and social benefits of fertilizer use. RESULTS: For above median meat consumption the risk of colon cancer doubles when exposed to drinking water exceeding 25 mg/L of nitrate (NO3) for more than ten years. We estimate the associated increase of incidence of colon cancer from nitrate contamination of groundwater based drinking water in EU11 at 3%. This corresponds to a population-averaged health loss of 2.9 euro per capita or 0.7 euro per kg of nitrate-N leaching from fertilizer. CONCLUSIONS: Our cost estimates indicate that current measures to prevent exceedance of 50 mg/L NO3 are probably beneficial for society and that a stricter nitrate limit and additional measures may be justified. The present assessment of social cost is uncertain because it considers only one type of cancer, it is based on one epidemiological study in Iowa, and involves various assumptions regarding exposure. Our results highlight the need for improved epidemiological studies.

The cost-effectiveness of hepatic venous pressure gradient monitoring in the prevention of recurrent variceal hemorrhage.

OBJECTIVE: Recurrent variceal hemorrhage is common following an initial bleed in patients with cirrhosis. The current standard of care for secondary prophylaxis is endoscopic band ligation (EBL). Combination of beta-blocker and nitrate therapy, guided by hepatic venous pressure gradient (HVPG) monitoring, is a novel alternative strategy. We sought to determine the cost-effectiveness of these competing strategies. METHODS: Decision analysis with Markov modeling was used to calculate the cost-effectiveness of three competing strategies: (1) EBL; (2) beta-blocker and nitrate therapy without HVPG monitoring (HVPG-); and (3) beta-blocker and nitrate therapy with HVPG monitoring (HVPG+). Patients in the HVPG+ strategy who failed to achieve an HVPG decline from medical therapy were offered EBL. Cost estimates were from a third-party payer perspective. The main outcome measure was the cost per recurrent variceal hemorrhage prevented. RESULTS: Under base-case conditions, the HVPG+ strategy was the most effective yet most expensive approach, followed by EBL and HVPG-. Compared to the EBL strategy, the HVPG+ strategy cost an incremental 5,974 dollars per recurrent bleed prevented. In a population with 100% compliance with all therapies, the incremental cost of HVPG-versus EBL fell to 5,270 dollars per recurrent bleed prevented. The model results were sensitive to the cost of EBL, the cost of HVPG monitoring, and the probability of medical therapy producing an adequate HVPG decline. CONCLUSIONS: Compared to EBL for the secondary prophylaxis of variceal rebleeding, combination medical therapy guided by HVPG monitoring is more effective and only marginally more expensive.

The prescription pattern of oral nitrates in coronary artery disease. Appropriateness and cost considerations.

OBJECTIVES: To evaluate the prescription patterns of oral nitrates in terms of appropriateness and cost in a community setting. METHODS: A period prevalence, descriptive, applied study. Data including age, gender, type of medication, dosage and cost were extracted from the database of the largest health maintenance organisation (HMO) in Israel. The study population included enrollees over 35 years of age who received oral nitrates at least once during the 12-month study period. RESULTS: Oral nitrates were prescribed for 8007 patients (mean age 72.85+/-9.59 years, male:female ratio 1:1). A total of 52,694 prescriptions were issued for 56,553 medications, of these 88.1% for mononitrates, which constituted 95% of the annual cost for patients and the HMO. The mean prescribed daily dose for the various drugs ranged from 30% less than to 50% more than the recommended dose. Combination therapy with at least two nitrates, which is not the recommended treatment, was given to 5% of the patients. The recommended alternative treatment will alleviate the financial burden for providers and patients. CONCLUSIONS: Improved prescription habits can provide enhanced quality as well as cost savings for patients and providers.

Predictors of large esophageal varices in patients with cirrhosis.

OBJECTIVE: Recent guidelines recommend that all cirrhotics undergo screening upper endoscopy to identify those patients at risk for bleeding from varices. However, this practice may not be cost effective as large esophageal varices are seen only in 9-36% of these patients. The aim of this study was to determine whether clinical variables were predictive of the presence of large esophageal varices. METHODS: This is a retrospective analysis of cirrhotics who had a screening upper endoscopy during an evaluation for liver transplantation at three different centers and who had not previously bled from varices. A multivariate model was derived on the combined cohort using logistic regression. Three hundred forty-six patients were eligible for the study. RESULTS: The prevalence of large esophageal varices was 20%. On multivariate analysis, splenomegaly detected by computed tomographic scan (odds ratio: 4.3; 95% confidence interval: 1.6-11.5) or by physical examination (odds ratio: 2.0; 95% confidence interval: 1.1-3.8), and low platelet count were independent predictors of large esophageal varices. On the basis of these variables, cirrhotics were stratified into high- and low-risk groups for the presence of large esophageal varices. Patients with a platelet count of > or = 88,000/mm3 (median value) and no splenomegaly by physical examination had a risk of large esophageal varices of 7.2%. Those with splenomegaly or platelet count < 88,000/mm3 had a risk of large esophageal varices of 28% (p < 0.0001). CONCLUSIONS: Our data show that clinical predictors could be used to stratify cirrhotic patients for the risk of large esophageal varices and such stratification could be used to improve the cost effectiveness of screening endoscopy.

Cost-effectiveness study of nitrate therapy using a decision analysis methodology.

The cost-assessment technology of decision analysis was applied to isosorbide dinitrate (ISDN), the standard therapy for angina; isosorbide mononitrate (ISMO), approved mid-1992; and nitroglycerin patches to measure the effect of economics on clinical practice and administrative choices. The evaluation was conducted to illustrate the utility of this method for decision makers in various sectors of the health care system, including physicians, pharmacy benefit administrators, formulary committees, and manufacturers. Findings indicate that despite a higher unit cost for ISMO, total anticipated treatment costs with this new long-acting nitrate are lower than those associated with ISDN (28%) and nitroglycerin patch (16%) therapy in patients with stable angina, and ISMO requires less dosing titration and is associated with fewer tolerance effects.