Type 2 Diabetes Patients Reach Target Glycemic Control Faster Using IDegLira than Either Insulin Degludec or Liraglutide Given Alone

BACKGROUND AND OBJECTIVES: The time-course when changes in glycemic control and body weight were first manifest in patients with type 2 diabetes mellitus (T2DM) treated with a combination of insulin degludec and liraglutide (IDegLira) was assessed, comparing IDegLira to its individual components. METHODS: Data from weeks 0–12 from two studies were analyzed, one comparing IDegLira to each component (DUAL I), and one comparing IDegLira to insulin degludec titrated to a maximum 50 units (DUAL II). Efficacy endpoints included glycated hemoglobin (HbA(1c)) and fasting plasma glucose (FPG) reduction, proportion of patients achieving HbA(1c) [<7.0 % (<53.0 mmol/mol)] and FPG (≤7.2 mmol/L) targets, and proportion achieving HbA(1c) target without hypoglycemia and without hypoglycemia and weight gain. RESULTS: Mean HbA(1c) was lower, and the proportion of patients reaching target HbA(1c) greater, with IDegLira versus comparators (both studies) at weeks 8 and 12. Proportions of patients reaching target HbA(1c) without hypoglycemia and without hypoglycemia and weight gain were higher for IDegLira versus insulin degludec, though not versus liraglutide. Mean FPG was lower with IDegLira, and the proportion achieving target FPG higher, versus components (both studies) from weeks 4–12. IDegLira was associated with mean weight reduction from weeks 4–12, although less than with liraglutide alone. Hypoglycemia occurred infrequently in weeks 0–12, with no difference in incidence between IDegLira and insulin degludec in either study. CONCLUSIONS: IDegLira reduces plasma glucose to a greater extent than its components, measurable within the first 12 weeks of therapy, and without weight gain or an increased hypoglycemia risk versus insulin degludec. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40261-016-0376-0) contains supplementary material, which is available to authorized users

A randomized trial of an early measles vaccine at 4½ months of age in Guinea-Bissau:sex-differential immunological effects

<div><p>Background</p><p>After measles vaccine (MV), all-cause mortality is reduced more than can be explained by the prevention of measles, especially in females.</p><p>Objective</p><p>We aimed to study the biological mechanisms underlying the observed non-specific and sex-differential effects of MV on mortality.</p><p>Methods</p><p>Within a large randomised trial of MV at 4.5 months of age blood samples were obtained before and six weeks after randomisation to early MV or no early MV. We measured concentrations of cytokines and soluble receptors from plasma (interleukin-1 receptor agonist (IL-1Ra), IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, soluble urokinase-type plasminogen activator receptor), and secreted cytokines (interferon-γ, TNF-α, IL-5, IL-10, IL-13, IL-17) after <i>in vitro</i> challenge with innate agonists and recall antigens. We analysed the effect of MV in multiple imputation regression, overall and stratified by sex. The majority of the infants had previously been enrolled in a randomised trial of neonatal vitamin A. <i>Post hoc</i> we explored the potential effect modification by neonatal vitamin A.</p><p>Results</p><p>Overall, MV versus no MV was associated with higher plasma MCP-1 levels, but the effect was only significant among females. Additionally, MV was associated with increased plasma IL-1Ra. MV had significantly positive effects on plasma IL-1Ra and IL-8 levels in females, but not in males. These effects were strongest in vitamin A supplemented infants. Vitamin A shifted the effect of MV in a pro-inflammatory direction.</p><p>Conclusions</p><p>In this explorative study we found indications of sex-differential effects of MV on several of the plasma biomarkers investigated; in particular MV increased levels in females, most strongly in vitamin A recipients. The findings support that sex and micronutrient supplementation should be taken into account when analysing vaccine effects.</p><p>Trial Registration</p><p>clinicaltrials.gov number <a href="http://clinicaltrials.gov/ct2/show/NCT00168545?term=00168545&rank=1" target="_blank">NCT 00168545</a></p></div

Comparing Whole-Genome Sequencing with Sanger Sequencing for spa Typing of Methicillin-Resistant Staphylococcus aureus

spa typing of methicillin-resistant Staphylococcus aureus (MRSA) has traditionally been done by PCR amplification and Sanger sequencing of the spa repeat region. At Hvidovre Hospital, Denmark, whole-genome sequencing (WGS) of all MRSA isolates has been performed routinely since January 2013, and an in-house analysis pipeline determines the spa types. Due to national surveillance, all MRSA isolates are sent to Statens Serum Institut, where the spa type is determined by PCR and Sanger sequencing. The purpose of this study was to evaluate the reliability of the spa types obtained by 150-bp paired-end Illumina WGS. MRSA isolates from new MRSA patients in 2013 (n = 699) in the capital region of Denmark were included. We found a 97% agreement between spa types obtained by the two methods. All isolates achieved a spa type by both methods. Nineteen isolates differed in spa types by the two methods, in most cases due to the lack of 24-bp repeats in the whole-genome-sequenced isolates. These related but incorrect spa types should have no consequence in outbreak investigations, since all epidemiologically linked isolates, regardless of spa type, will be included in the single nucleotide polymorphism (SNP) analysis. This will reveal the close relatedness of the spa types. In conclusion, our data show that WGS is a reliable method to determine the spa type of MRSA

Flow chart of the immunological study.

<p>Numbers in parentheses designates group assignment, early MV or control group, respectively.</p

Effect of MV on plasma biomarkers stratified by vitamin A and sex.

<p>VAS: Vitamin A supplementation at birth. Effect estimates or interactions with a significance level below p = 0.05 after adjustment for multiple testing are highlighted in bold writing.</p>#<p>P value for interaction between MV and sex for vitamin A recipients or non-recipients, respectively.</p><p>^*Estimates of measles vaccine effect are obtained by Poisson regression due to low number of detectables measurements (<50%).</p

Effect of MV on plasma biomarkers; overall and stratified by sex.

<p>The percentage of non-detectable measurements (ND, below lower limit of detection) is presented for baseline (BL) and follow-up (FU), respectively. Effect estimates or interactions with a significance level below p = 0.05 after adjustment for multiple testing are highlighted in bold writing.</p>#<p>P value for interaction between MV and sex.</p><p>*Estimates of measles vaccine effect are obtained by Poisson regression due to low number of detectable measurements (<50%).</p