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 .)

Insights on HPV Vaccination in the United States from Mothers\u27 Comments on Facebook Posts in a Randomized Trial.

In the United States, parents\u27 health beliefs affect HPV vaccination decisions for children. Our team acquired insights into mothers\u27 health beliefs from their reactions and comments to posts on HPV vaccination in a social media adolescent health campaign in a randomized trial (n = 881 mothers; 63.1% reported daughters had 1+ doses of the HPV vaccine) evaluating communication intended to reduce daughters\u27 indoor tanning. A total of 10 HPV vaccination messages in didactic (n = 7) and narrative (n = 3) formats were posted on vaccination need, uptake, and effectiveness and stories of young women who died from cervical cancer and a mother\u27s decision to vaccinate her daughters. These posts received 28 reactions (like, love, and sad buttons; mean = 2.8 per post) and 80 comments (mean = 8.0 per post). More comments were favorable (n = 43) than unfavorable (n = 34). Data was not collected on views for posts. The most common favorable comment reported that daughters were vaccinated (n = 31). Unfavorable comments cited safety concerns, lack of physician support, distrust of pro-vaccine sources, and increased sexual activity of daughters. Mothers posting unfavorable (18.2%) as opposed to favorable (78.6%) comments or not commenting (64.0%) were less likely to have had their daughters vaccinated (chi-square = 22.27, p \u3c 0.001). Favorable comments often did not state reasons for vaccinating. Concerns about lack of vaccine safety remain a barrier. Mothers may express distrust in pro-vaccine sources to reduce discomfort with not vaccinating daughters to reduce their risk for HPV infection. Many mothers who remained silent had vaccinated daughters, which suggests they did not resisit HPV vaccination

Atmospheric Reaction Systems as Null-Models to Identify Structural Traces of Evolution in Metabolism

The metabolism is the motor behind the biological complexity of an organism. One problem of characterizing its large-scale structure is that it is hard to know what to compare it to. All chemical reaction systems are shaped by the same physics that gives molecules their stability and affinity to react. These fundamental factors cannot be captured by standard null-models based on randomization. The unique property of organismal metabolism is that it is controlled, to some extent, by an enzymatic machinery that is subject to evolution. In this paper, we explore the possibility that reaction systems of planetary atmospheres can serve as a null-model against which we can define metabolic structure and trace the influence of evolution. We find that the two types of data can be distinguished by their respective degree distributions. This is especially clear when looking at the degree distribution of the reaction network (of reaction connected to each other if they involve the same molecular species). For the Earth's atmospheric network and the human metabolic network, we look into more detail for an underlying explanation of this deviation. However, we cannot pinpoint a single cause of the difference, rather there are several concurrent factors. By examining quantities relating to the modular-functional organization of the metabolism, we confirm that metabolic networks have a more complex modular organization than the atmospheric networks, but not much more. We interpret the more variegated modular arrangement of metabolism as a trace of evolved functionality. On the other hand, it is quite remarkable how similar the structures of these two types of networks are, which emphasizes that the constraints from the chemical properties of the molecules has a larger influence in shaping the reaction system than does natural selection