Longitudinal medical resources and costs among type 2 diabetes patients participating in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS)

Aims: TECOS, a cardiovascular safety trial (ClinicalTrials.gov identifier: NCT00790205) involving 14 671 patients with type 2 diabetes and cardiovascular disease, demonstrated that sitagliptin was non-inferior to placebo for the primary composite cardiovascular outcome when added to best usual care. This study tested hypotheses that medical resource use and costs differed between these 2 treatment strategies. Materials and methods: Information concerning medical resource use was collected on case report forms throughout the trial and was valued using US costs for: Medicare payments for hospitalizations, medical procedures and outpatient visits, and wholesale acquisition costs (WAC) for diabetes-related medications. Hierarchical generalized linear models were used to compare resource use and US costs, accounting for variable intercountry practice patterns. Sensitivity analyses included resource valuation using English costs for a UK perspective. Results: There were no significant differences in hospitalizations, inpatient days, medical procedures, or outpatient visits during follow-up (mean and median 3.0 years in both groups). Hospitalization rates appeared to diverge after 2 years, with lower rates among sitagliptin-treated vs placebo patients after 2.5 years (relative rate, 0.90 [95% CI, 0.83-0.97]; P =.01). Mean medical costs, exclusive of study medication, were 11 937 USD in the sitagliptin arm and 12 409 USD in the placebo arm (P =.06). Mean sitagliptin costs based on undiscounted WAC were 9978 USD per patient. Differential UK total costs including study drug costs were smaller (911 GBP), primarily because of lower mean costs for sitagliptin (1072 GBP). Conclusions: Lower hospitalization rates across time with sitagliptin slightly offset sitagliptin treatment costs over 3 years in type 2 diabetes patients at high risk for cardiovascular events

Particle acceleration mechanisms

We review the possible mechanisms for production of non-thermal electrons which are responsible for non-thermal radiation in clusters of galaxies. Our primary focus is on non-thermal Bremsstrahlung and inverse Compton scattering, that produce hard X-ray emission. We briefly review acceleration mechanisms and point out that in most astrophysical situations, and in particular for the intracluster medium, shocks, turbulence and plasma waves play a crucial role. We consider two scenarios for production of non-thermal radiation. The first is hard X-ray emission due to non-thermal Bremsstrahlung by nonrelativistic particles. Non-thermal tails are produced by accelerating electrons from the background plasma with an initial Maxwellian distribution. However, these tails are accompanied by significant heating and they are present for a short time of <10^6 yr, which is also the time that the tail will be thermalised. Such non-thermal tails, even if possible, can only explain the hard X-ray but not the radio emission which needs GeV or higher energy electrons. For these and for production of hard X-rays by the inverse Compton model, we need the second scenario where there is injection and subsequent acceleration of relativistic electrons. It is shown that a steady state situation, for example arising from secondary electrons produced from cosmic ray proton scattering by background protons, will most likely lead to flatter than required electron spectra or it requires a short escape time of the electrons from the cluster. An episodic injection of relativistic electrons, presumably from galaxies or AGN, and/or episodic generation of turbulence and shocks by mergers can result in an electron spectrum consistent with observations but for only a short period of less than one billion years.Comment: 22 pages, 5 figures, accepted for publication in Space Science Reviews, special issue "Clusters of galaxies: beyond the thermal view", Editor J.S. Kaastra, Chapter 11; work done by an international team at the International Space Science Institute (ISSI), Bern, organised by J.S. Kaastra, A.M. Bykov, S. Schindler & J.A.M. Bleeke

Cold Plus Hot Dark Matter Cosmology in the Light of Solar and Atmospheric Neutrino Oscillations

We explore the implications of possible neutrino oscillations, as indicated by the solar and atmospheric neutrino experiments, for the cold plus hot dark matter scenario of large scale structure formation. We find that there are essentially three distinct schemes that can accommodate the oscillation data and which also allow for dark matter neutrinos. These include (i) three nearly degenerate (in mass) neutrinos, (ii) non-degenerate masses with $\nu_\tau$ in the eV range, and (iii) nearly degenerate $\nu_\mu-\nu_\tau$ pair (in the eV range), with the additional possibility that the electron neutrino is cosmologically significant. The last two schemes invoke a `sterile' neutrino which is light (< or ~ eV). We discuss the implications of these schemes for $\bar{\nu}_\mu - \bar{\nu}_e$ and $\nu_\mu - \nu_\tau$ oscillation, and find that scheme (ii) in particular, predicts them to be in the observable range. As far as structure formation is concerned, we compare the one neutrino flavor case with a variety of other possibilities, including two and three degenerate neutrino flavors. We show, both analytically and numerically, the effects of these neutrino mass scenarios on the amplitude of cosmological density fluctuations. With a Hubble constant of 50 km s$^{-1}$ Mpc$^{-1}$, a spectral index of unity, and $\Omega_{baryon} = 0.05$, the two and three flavor scenarios fit the observational data marginally better than the single flavor scheme. However, taking account of the uncertainties in these parameters, we show that it is premature to pick a clear winner.Comment: 1 LaTEX file plus 1 uuencoded Z-compressed tar file with 3 postscript figure

An Observational Overview of Solar Flares

We present an overview of solar flares and associated phenomena, drawing upon a wide range of observational data primarily from the RHESSI era. Following an introductory discussion and overview of the status of observational capabilities, the article is split into topical sections which deal with different areas of flare phenomena (footpoints and ribbons, coronal sources, relationship to coronal mass ejections) and their interconnections. We also discuss flare soft X-ray spectroscopy and the energetics of the process. The emphasis is to describe the observations from multiple points of view, while bearing in mind the models that link them to each other and to theory. The present theoretical and observational understanding of solar flares is far from complete, so we conclude with a brief discussion of models, and a list of missing but important observations.Comment: This is an article for a monograph on the physics of solar flares, inspired by RHESSI observations. The individual articles are to appear in Space Science Reviews (2011

Reconstructing the environmental conditions experienced by early modern humans at Tam Pà Ling (northeast Laos) using higher plant wax biomarkers

International audienc

Effect of intensive multifactorial treatment on the intima-media thickness of large arteries in patients with new-onset type 2 diabetes mellitus*

Objective: To quantify the changes in blood glucose, blood lipids, blood pressure, and the intima-media thickness (IMT) of large arteries in patients with new-onset type 2 diabetes mellitus who received either intensive multifactorial treatment or conventional treatment. Methods: Two-hundred and ten patients with new-onset type 2 diabetes mellitus were randomly assigned to two groups: an intensive treatment group (n=110) and a conventional treatment group (n=100). Fasting blood glucose (FBG), glycosylated hemoglobin A1c (HbA1c), blood pressure, blood lipids [total cholesterol (TC), triglyceride (TG), low-density lipoprotein C (LDL-C), and high-density lipoprotein C (HDL-C)], and IMTs of large arteries (carotid, iliac, and femoral arteries) were determined before and at one and two years after starting treatment. The patients in the conventional treatment group received routine diabetes management in our outpatient department. Targets were established for patients in the intensive treatment group. Their blood glucose, blood lipids, and blood pressure levels were regularly monitored and therapeutic regimens were adjusted for those whose measurements did not meet the target values until all the parameters met the established targets. Within-group and between-group differences were evaluated. Results: A significantly greater percentage of patients in the intensive treatment group had LDL-C levels that reached the target value one year after starting treatment than those in the conventional treatment group (52.04% vs. 33.33%, P<0.05). No significant differences were found between groups for FBG, HbA1c, blood pressure, TG, TC, or HDL-C. The percentages of patients with TG (51.02% vs. 34.48%), TC (52.04% vs. 33.33%), and LDL-C (61.22% vs. 43.67%) who met the respective target values in the intensive treatment group were all significantly higher than the corresponding percentages in the conventional treatment group two years after starting treatment (P<0.05). There were no significant differences in the percentages of patients with FBG, HbA1c, and blood pressure values meeting the respective targets between the groups at the two-year follow-up. One year after starting treatment, the LDL-C level, diastolic blood pressure (DBP), and the IMTs of the femoral and iliac arteries of the intensive treatment group were significantly lower compared to those of the conventional treatment group (P<0.05), although there was no significant difference in other metabolic parameters. Two years after starting treatment, the TC, LDL-C, blood pressure [systolic blood pressure (SBP) and DBP], and the IMTs of the carotid and femoral arteries of the intensive treatment group were significantly lower than those of the conventional treatment group (P<0.05). No significant differences in other metabolic parameters existed between the two groups two years after starting treatment. Conclusions: Early comprehensive and intensive treatment of type 2 diabetes mellitus can delay or even reverse the increase in IMT of large arteries. Lowering blood pressure and blood lipid regulation in patients with type 2 diabetes mellitus have great significance in decreasing the risk of diabetes-related macrovascular lesions