Basal Insulin Regimens for Adults with Type 1 Diabetes Mellitus : A Cost-Utility Analysis

Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.OBJECTIVES: To assess the cost-effectiveness of basal insulin regimens for adults with type 1 diabetes mellitus in England. METHODS: A cost-utility analysis was conducted in accordance with the National Institute for Health and Care Excellence reference case. The UK National Health Service and personal and social services perspective was used and a 3.5% discount rate was applied for both costs and outcomes. Relative effectiveness estimates were based on a systematic review of published trials and a Bayesian network meta-analysis. The IMS CORE Diabetes Model was used, in which net monetary benefit (NMB) was calculated using a threshold of £20,000 per quality-adjusted life-year (QALY) gained. A wide range of sensitivity analyses were conducted. RESULTS: Insulin detemir (twice daily) [iDet (bid)] had the highest mean QALY gain (11.09 QALYs) and NMB (£181,456) per patient over the model time horizon. Compared with the lowest cost strategy (insulin neutral protamine Hagedorn once daily), it had an incremental cost-effectiveness ratio of £7844/QALY gained. Insulin glargine (od) [iGlarg (od)] and iDet (od) were ranked as second and third, with NMBs of £180,893 and £180,423, respectively. iDet (bid) remained the most cost-effective treatment in all the sensitivity analyses performed except when high doses were assumed (>30% increment compared with other regimens), where iGlarg (od) ranked first. CONCLUSIONS: iDet (bid) is the most cost-effective regimen, providing the highest QALY gain and NMB. iGlarg (od) and iDet (od) are possible options for those for whom the iDet (bid) regimen is not acceptable or does not achieve required glycemic control.Peer reviewe

Sex differences in redox state, autophagy and lysosomal function

Modifications of the normal redox state are connected with numerous diseases and conditions such as cardiovascular diseases, diabetes mellitus and its complications, liver diseases, and aging which are characterized by numerous sex differences. Evidences suggest that redox state might be different in males and females. Autophagy is crucial for the maintaining cellular homeostasis process whereby cytoplasmic components are delivered to lysosomes for degradation. Alteration in constitutive autophagy is implicated in many pathological conditions, including heart diseases, diabetes mellitus and its complications, and liver diseases. A cross-talk between ROS and autophagy has been described. The current study was conducted to investigate the influence of sex on lipid and protein oxidation and autophagic response in the heart, the liver and the kidney obtained from young adult healthy male and female rats. 7 week old Sprague-Dawley rats were used to obtain heart, liver and kidneys. Malondialdehyde (MDA), and carbonylated proteins were measured by spectrophotometric methods for redox state assessment. The autophagy biomarkers Beclin-1, and microtubule-associated protein 1 light chain 3 (LC3), the mammalian target of rapamycin (mTOR; checkpoint in autophagic process), and the lysosomal associated membrane protein (LAMP-1; biomarker of lysosomes) were evaluated by Western blotting. Immunofluorescence analysis was also performed for LC3 and LAMP-1 colocalization. In the heart, Beclin-1, LC3-II/LC3-I were higher in males than in females suggesting that male heart have a major constitutive autophagy and this was linked with higher levels of carbonyl groups, indicating that protein oxidation could play a role. In the liver, it was found that LAMP-1 was higher in males and greatly colocalized with LC3 indicating a larger number of autophagolysosomes. None of the above parameters was significantly different in the kidneys of both sexes with the exception of MDA, which was significantly higher in females. These results suggest that the sex determinant affects the autophagy process and oxidation of proteins and lipids in an organ specific manner. It seems that the protein oxidation is more linked with constitutive autophagy, at least in cardiac ventricles, in comparison with lipid peroxidation

Efficacy, Safety, and Tolerability of Treatments for Systemic Sclerosis-Related Interstitial Lung Disease: A Systematic Review and Network Meta-Analysis

Background: There is a paucity of head-to-head comparisons of the efficacy and harms of pharmacological treatments for systemic sclerosis-related interstitial lung disease (SSc-ILD). Methods: We conducted a network meta-analysis (NMA) in order to compare the effects of different treatments with the placebo on change in forced vital capacity (FVC), change in diffusion lung capacity for CO (DLCO), serious adverse events (SAEs), discontinuation for adverse events and mortality in SSc-ILD. Standardized mean difference (SMD) and log odds ratio were estimated using NMA with fixed effects. Results: Nine randomized clinical trials (926 participants) comparing eight interventions and the placebo for an average follow-up of one year were included. Compared to the placebo, only rituximab significantly reduced FVC decline (SMD (95% CI) = 1.00 (0.39 to 1.61)). Suitable data on FVC outcome for nintedanib were not available for the analysis. No treatments influenced DLCO. Safety and mortality were also not different across treatments and the placebo, although there were few reported events. Cyclophosphamide and pomalidomide were less tolerated than the placebo, mycophenolate, and nintedanib. Conclusion: Only rituximab significantly reduced lung function decline compared to the placebo. However, direct head-to-head comparison studies are required to confirm these findings and to better determine the safety profile of various treatments

The cosipy library: COSI's high-level analysis software

The Compton Spectrometer and Imager (COSI) is a selected Small Explorer (SMEX) mission launching in 2027. It consists of a large field-of-view Compton telescope that will probe with increased sensitivity the under-explored MeV gamma-ray sky (0.2-5 MeV). We will present the current status of cosipy, a Python library that will perform spectral and polarization fits, image deconvolution, and all high-level analysis tasks required by COSI's broad science goals: uncovering the origin of the Galactic positrons, mapping the sites of Galactic nucleosynthesis, improving our models of the jet and emission mechanism of gamma-ray bursts (GRBs) and active galactic nuclei (AGNs), and detecting and localizing gravitational wave and neutrino sources. The cosipy library builds on the experience gained during the COSI balloon campaigns and will bring the analysis of data in the Compton regime to a modern open-source likelihood-based code, capable of performing coherent joint fits with other instruments using the Multi-Mission Maximum Likelihood framework (3ML). In this contribution, we will also discuss our plans to receive feedback from the community by having yearly software releases accompanied by publicly-available data challenges

The Compton Spectrometer and Imager

The Compton Spectrometer and Imager (COSI) is a NASA Small Explorer (SMEX) satellite mission in development with a planned launch in 2027. COSI is a wide-field gamma-ray telescope designed to survey the entire sky at 0.2-5 MeV. It provides imaging, spectroscopy, and polarimetry of astrophysical sources, and its germanium detectors provide excellent energy resolution for emission line measurements. Science goals for COSI include studies of 0.511 MeV emission from antimatter annihilation in the Galaxy, mapping radioactive elements from nucleosynthesis, determining emission mechanisms and source geometries with polarization measurements, and detecting and localizing multimessenger sources. The instantaneous field of view for the germanium detectors is >25% of the sky, and they are surrounded on the sides and bottom by active shields, providing background rejection as well as allowing for detection of gamma-ray bursts and other gamma-ray flares over most of the sky. In the following, we provide an overview of the COSI mission, including the science, the technical design, and the project status.Comment: 8 page

Selective modifications in GAD67 mRNA levels in striatonigral and striatopallidal pathways correlate to dopamine agonist priming in 6-hydroxydopamine-lesioned rats

The present study investigated long-term alterations in striatal gene expression after single exposure of unilaterally 6-hydroxydopamine-lesioned rats to different dopamine agonists (priming). Rats were primed with the D1 agonist SKF38393 (10 mg/kg), the D2/D3 agonist quinpirole (0.2 mg/kg), the dopamine precursor L-DOPA (50 mg/kg) or with vehicle (drug-naive), and GAD67, dynorphin and enkephalin mRNAs were evaluated in the striatum by in situ hybridization, 3 days after priming. To evaluate GAD67 mRNA in striatonigral and striatopallidal neurons, identified as enkephalin (-) and (+) neurons, double-labelling in situ hybridization was used. Drug-naive lesioned rats showed an increase in GAD67 mRNA in enkephalin (-) and (+) neurons, an increase in enkephalin and a decrease in dynorphin mRNAs. Priming with either SKF38393 or quinpirole further increased GAD67 mRNA in enkephalin (-) and (+) neurons, however, while SKF38393 produced a high and unbalanced activation toward enkephalin (-) neurons, after quinpirole the increase was of low intensity and similar in the two pathways. Dynorphin mRNA was increased by SKF38393 but not by quinpirole, whereas enkephalin mRNA was not changed by either priming. L-DOPA produced a high and similar increase in GAD67 mRNA in enkephalin (-) and (+) neurons. Priming differentially affected peptides and GAD67 mRNA in striatopallidal and striatonigral neurons depending on the dopamine agonist used. The degree of enduring overactivity of the striatopallidal and striatonigral pathways may be related to the ability of L-DOPA and D1 or D2/D3 receptor agonists to prime motor behavioural responses and to produce dyskinetic side-effects