Saxagliptin in combination with Metformin or Sulfonylurea achieved HbA1c goals

Diabetes affects over 1.2 million people in Australia. Saxagliptin (SAXA) is a potent, selective dipeptidyl peptidase-4 (DPP-4) inhibitor. Three 24-week phase 3 studies assessed efficacy and safety of SAXA as add-on to Metformin (MET), as initial combination therapy with MET, or as add-on to the sulfonylurea (SU) glyburide (GLY) in patients (pts) with type 2 diabetes (T2D) and inadequate glycaemic control. In the add-on to MET study, 743 pts inadequately controlled on MET alone (HbA1c 7.0%–10.0%; mean baseline (BL) HbA1c 8.0%; mean T2D duration 6.5 yrs) were randomised to SAXA or placebo (PBO) with ongoing dose of MET. In the initial combination study, 1306 drug naïve pts (HbA1c8.0%–12.0%; mean BL HbA1c 9.5%; mean T2D duration 1.7 yrs) were randomised to SAXA + MET, SAXA + PBO, or MET + PBO. In the add-on to SU study, 768 pts inadequately controlled on SU alone (HbA 1c7.5%–10.0%; mean BL HbA1c 8.4%; mean T2D duration 6.9 yrs) were randomised to SAXA or uptitrated GLY + PBO in addition to open-label GLY. Efficacy analyses used ANCOVA model. The proportion of patients reaching HbA1c goals used Fisher exact test. HbA1c goals were predefined for each study. In all three studies, statistically significantly greater proportions of SAXA-treated pts achieved HbA1c goals of <7.0% and ≤6.5% vs. control at 24 wks (Table). Twice as many pts treated with SAXA added to MET or GLY achieved the HbA1c goal of <7% and ≤6.5% relative to control at 24 wks. For all three studies, the frequency of adverse events (AEs) was generally similar for SAXA vs. control (Table). SAXA 5 mg + MET as either add-on or initial combination therapy, and SAXA 5 mg + SU significantly improved glycaemic control, was well tolerated and achieved predefined HbA1c goals vs. control in more patients

Surface skyrmions and dual topological Hall effect in antiferromagnetic topological insulator EuCd2_2As2_2

In this work, we synthesized single crystal of EuCd$_2$As$_2$, which exhibits A-type antiferromagnetic (AFM) order with in-plane spin orientation below $T_N$ = 9.5~K.Optical spectroscopy and transport measurements suggest its topological insulator (TI) nature with an insulating gap around 0.1eV. Remarkably, a dual topological Hall resistivity that exhibits same magnitude but opposite signs in the positive to negative and negative to positive magnetic field hysteresis branches emerges below 20~K. With magnetic force microscopy (MFM) images and numerical simulations, we attribute the dual topological Hall effect to the N\'{e}el-type skyrmions stabilized by the interactions between topological surface states and magnetism, and the sign reversal in different hysteresis branches indicates potential coexistence of skyrmions and antiskyrmions. Our work uncovers a unique two-dimensional (2D) magnetism on the surface of intrinsic AFM TI, providing a promising platform for novel topological quantum states and AFM spintronic applications.Comment: 7 pages, 3 figure

Nicotine Dependence among Rural-Urban Migrants in China

<p>Abstract</p> <p>Background</p> <p>The complex mechanism of nicotine dependency makes it challenging to evaluate dependence or progress towards dependence. The aim of this study was to estimate nicotine dependence levels and identify determinants of dependence among Chinese rural-urban migrants.</p> <p>Methods</p> <p>Multi-stage systematic sampling was used to select 4,198 rural-urban migrants aged 18 years or older from three metropolises in China. A structured questionnaire was administered during face-to-face interviews. Nicotine dependence among participants was assessed by means of the six-item Mandarin Chinese Version of the Fagerström Test for Nicotine Dependence (CFTND). Determinants of dependence were analyzed using multivariate analysis of variance (MANOVA).</p> <p>Results</p> <p>Among 4,198 participants, estimated current, daily, and occasional smoking rates were 28.3%, 21.2%, and 7.1%, respectively. The CTFND score for the 894 daily smokers was 3.39(SD: 2.32). MANOVA showed that work type, age at first migration, length of migration, and number of cities ever lived were associated with nicotine dependence.</p> <p>Conclusion</p> <p>A migratory lifestyle is associated with nicotine dependence. Results could inform the design of tobacco control programs that target Chinese rural-urban migrant workers as a special at-risk population.</p

One-Step UV-Induced Synthesis of Polypyrrole/Ag Nanocomposites at the Water/Ionic Liquid Interface

Polpyrrole (PPy)/Ag nanocomposites were successfully synthesized at the interface of water and ionic liquid by one-step UV-induced polymerization. Highly dispersed PPy/Ag nanoparticles were obtained by controlling the experimental conditions. The results of Fourier-transform infrared spectroscopy, X-ray diffraction, transmission electron microscopy and X-ray photoelectron spectroscopy revealed that the UV-induced interface polymerization leaded to the formation of PPy incorporating silver nanoparticles. It was also found that the electrical conductivity of PPy/Ag nanocomposite was about 100 times higher than that of pure PPy

Irish general practitioner attitudes toward decriminalisation and medical use of cannabis: results from a national survey.

BACKGROUND: Governmental debate in Ireland on the de facto decriminalisation of cannabis and legalisation for medical use is ongoing. A cannabis-based medicinal product (Sativex®) has recently been granted market authorisation in Ireland. This unique study aimed to investigate Irish general practitioner (GP) attitudes toward decriminalisation of cannabis and assess levels of support for use of cannabis for therapeutic purposes (CTP). METHODS: General practitioners in the Irish College of General Practitioner (ICGP) database were invited to complete an online survey. Anonymous data yielded descriptive statistics (frequencies, percentages) to summarise participant demographic information and agreement with attitudinal statements. Chi-square tests and multi-nominal logistic regression were included. RESULTS: The response rate was 15% (n = 565) which is similar to other Irish national GP attitudinal surveys. Over half of Irish GPs did not support the decriminalisation of cannabis (56.8%). In terms of gender, a significantly higher proportion of males compared with females (40.6 vs. 15%; p < 0.0001) agreed or strongly agreed with this drug policy approach. A higher percentage of GPs with advanced addiction specialist training (level 2) agreed/strongly agreed that cannabis should be decriminalised (54.1 vs. 31.5%; p = 0.021). Over 80% of both genders supported the view that cannabis use has a significant effect on patients' mental health and increases the risk of schizophrenia (77.3%). Over half of Irish GPs supported the legalisation of cannabis for medical use (58.6%). A higher percentage of those who were level 1-trained (trained in addiction treatment but not to an advanced level) agreed/strongly agreed cannabis should be legalised for medical use (p = 0.003). Over 60% agreed that cannabis can have a role in palliative care, pain management and treatment of multiple sclerosis (MS). In the regression response predicator analysis, females were 66.2% less likely to agree that cannabis should be decriminalised, 42.5% less likely to agree that cannabis should be legalised for medical use and 59.8 and 37.6% less likely to agree that cannabis has a role in palliative care and in the treatment of multiple sclerosis (respectively) than males. CONCLUSIONS: The majority of Irish GPs do not support the present Irish governmental drug policy of decriminalisation of cannabis but do support the legalisation of cannabis for therapeutic purposes. Male GPs and those with higher levels of addiction training are more likely to support a more liberal drug policy approach to cannabis for personal use. A clear majority of GPs expressed significant concerns regarding both the mental and physical health risks of cannabis use. Ongoing research into the health and other effects of drug policy changes on cannabis use is required

The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations

International audienceBACKGROUND:Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at increased BC risk in the immediate years following an FTP. No large prospective studies, however, have examined whether the number and timing of pregnancies are associated with BC risk for BRCA1 and BRCA2 mutation carriers.METHODS:Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events are associated with BC risk for mutation carriers using a retrospective cohort (5707 BRCA1 and 3525 BRCA2 mutation carriers) and a prospective cohort (2276 BRCA1 and 1610 BRCA2 mutation carriers), separately for each cohort and the combined prospective and retrospective cohort.RESULTS:For BRCA1 mutation carriers, there was no overall association with parity compared with nulliparity (combined hazard ratio [HRc] = 0.99, 95% confidence interval [CI] = 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRc = 0.79, 95% CI = 0.69 to 0.91; HRc = 0.70, 95% CI = 0.59 to 0.82; HRc = 0.50, 95% CI = 0.40 to 0.63, for 2, 3, and ≥4 FTPs, respectively, P trend < .0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort P trend = .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] = 1.69, 95% CI = 1.09 to 2.62). For BRCA2 mutation carriers, being parous was associated with a 30% increase in BC risk (HRc = 1.33, 95% CI = 1.05 to 1.69), and there was no apparent decrease in risk associated with multiparity except for having at least 4 FTPs vs. 1 FTP (HRc = 0.72, 95% CI = 0.54 to 0.98).CONCLUSIONS:These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers