Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes.

Abstract BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo. (Funded by Amylin Pharmaceuticals; EXSCEL ClinicalTrials.gov number, NCT01144338 .)

Soil solarization and sustainable agriculture

Pesticide treatments provide an effective control of soilborne pests in vegetable and fruit crops, but their toxicity to animals and people and residual toxicity in plants and soil, and high cost make their use hazardous and economically expensive. Moreover, actual environmental legislation is imposing severe restrictions on the use or the total withdrawal of most soil-applied pesticides. Therefore, an increasing emphasis has been placed on the use of nonchemical or pesticide-reduced control methods. Soil solarization is a nonpesticidal technique which kills a wide range of soil pathogens, nematodes, and weed seeds and seedlings through the high soil temperatures raised by placing plastic sheets on moist soil during periods of high ambient temperature. Direct thermal inactivation of target organisms was found to be the most important mechanism of solarization biocidal effect, contributed also by a heat-induced release of toxic volatile compounds and a shift of soil microflora to microorganisms antagonist of plant pathogens. Soil temperature and moisture are critical variables in solarization thermal effect, though the role of plastic film is also fundamental for the solarizing process, as it should increase soil temperature by allowing the passage of solar radiation while reducing energetic radiative and convective losses. Best solarizing properties were shown by low-density or vynilacetate- coextruded polyethylene formulations, but a wide range of plastic materials were documented as also suitable to soil solarization. Solar heating was normally reported to improve soil structure and increase soil content of soluble nutrients, particularly dissolved organic matter, inorganic nitrogen forms, and available cations, and shift composition and richness of soil microbial communities, with a marked increase of plant growth beneficial, plant pathogen antagonistic or root quick recolonizer microorganisms. As a consequence of these effects, soil solarization was largely documented to increase plant growth and crop yield and quality along more than two crop cycles. Most important fungal plant pathogenic species were found strongly suppressed by the solarizing treatment, as several studies documented an almost complete eradication of economically relevant pathogens, such as Fusarium spp., Phytophthora spp., Pythium spp., Sclerotium spp., Verticillium spp., and their related diseases in many vegetable and fruit crops and in different experimental conditions. Beneficial effects on fungal pathogens were stated to commonly last for about two growing seasons and also longer. Soil solarization demonstrated to be effective for the control of bacterial diseases caused by Agrobacterium spp., Clavibacter michiganensis and Erwinia amylovora, but failed to reduce incidence of tomato diseases caused by Pseudomonas solanacearum. Solarization was generally found less effective on phytoparasitic nematodes than on other organisms, due to their quicker soil recolonization compared to fungal pathogens and weeds, but field and greenhouse studies documented consistant reductions of root-knot severity and population densities of root-knot nematodes, Meloidogyne spp., as well as a satisfactory control of cyst-nematode species, such as Globodera rostochiensis and Heterodera carotae, and bulb nematode Ditylenchus dipsaci. Weeds were variously affected by solar heating, as annual species were generally found almost completely suppressed and perennial species more difficult to control, due to the occurrence deep propagules not exposed to lethal temperature. Residual effect of solarization on weeds was found much more pronounced than on nematodes and most fungal pathogens. Soil solarization may be perfect fit for all situations in which use of pesticides is restricted or completely banned, such as in organic production, or in farms located next to urban areas, or specialty crops with few labeled pesticides. Advantages of solarization also include economic convenience, as demonstrated by many comparative benefit/cost analyses, ease of use by growers, adaptability to many cropping systems, and a full integration with other control tools, which makes this technique perfectly compatible with principles of integrated pest management required by sustainable agriculture