Effects of oral glucose-lowering drugs on long term outcomes in patients with diabetes mellitus following myocardial infarction not treated with emergent percutaneous coronary intervention - a retrospective nationwide cohort study

<p>Abstract</p> <p>Background</p> <p>The optimum oral pharmacological treatment of diabetes mellitus to reduce cardiovascular disease and mortality following myocardial infarction has not been established. We therefore set out to investigate the association between individual oral glucose-lowering drugs and cardiovascular outcomes following myocardial infarction in patients with diabetes mellitus not treated with emergent percutaneous coronary intervention.</p> <p>Materials and methods</p> <p>All patients aged 30 years or older receiving glucose-lowering drugs (GLDs) and admitted with myocardial infarction (MI) not treated with emergent percutaneous coronary intervention in Denmark during 1997-2006 were identified by individual-level linkage of nationwide registries of hospitalizations and drug dispensing from pharmacies. Multivariable Cox regression models adjusted for age, sex, calendar year, comorbidity, and concomitant pharmacotherapy were used to assess differences in the composite endpoint of non-fatal MI and cardiovascular mortality between individual GLDs, using metformin monotherapy as reference.</p> <p>Results</p> <p>The study comprised 9876 users of GLDs admitted with MI. The mean age was 72.3 years and 56.5% of patients were men. A total of 3649 received sulfonylureas and 711 received metformin at admission. The average length of follow-up was 2.2 (SD 2.6) years. A total of 6,171 patients experienced the composite study endpoint. The sulfonylureas glibenclamide, glimepiride, glipizide, and tolbutamide were associated with increased risk of cardiovascular mortality and/or nonfatal MI with hazard ratios [HRs] of 1.31 (95% confidence interval [CI] 1.17-1.46), 1.19 (1.06-1.32), 1.25 (1.11-1.42), and 1.18 (1.03-1.34), respectively, compared with metformin. Gliclazide was the only sulfonylurea not associated with increased risk compared with metformin (HR 1.03 [0.88-1.22]).</p> <p>Conclusions</p> <p>In patients with diabetes mellitus admitted with MI not treated with emergent percutaneous coronary intervention, monotherapy treatment with the sulfonylureas glibenclamide, glimepiride, glipizide, and tolbutamide was associated with increased cardiovascular risk compared with metformin monotherapy.</p

Exploring disease-related and treatment-related issues and concerns experienced by adults with spondyloarthritis, inflammatory bowel disease and psoriasis to identify unmet needs: a qualitative clinical concept mapping study

OBJECTIVES: Exploring patients' perspectives for significant factors of relevance in living with a chronic disease is important to discover unmet needs and challenges. The primary objective of this study was to explore disease-related and treatment-related issues and concerns experienced by adults with spondyloarthropathies (SpA) and associated diseases. As a secondary objective, we wanted to explore whether these factors were generic or disease dependent.DESIGN: We used group concept mapping (GCM), a validated qualitative method, to identify disease-related and treatment-related issues and concerns. Participants generated statements in the GCM workshops and organised them into clusters to develop concepts. Furthermore, participants rated each statement for importance from 1: 'not important at all' to 5: 'of great importance'.SETTING: Participants were recruited during routine care at the outpatient clinic at the hospitals in the period from May 2018 to July 2022.PARTICIPANTS: Eligible participants were adults ≥18 years and diagnosed with axial spondyloarthritis (AxSpA), psoriatic arthritis (PsA), psoriasis (PsO) or inflammatory bowel disease -split into Crohn's disease (CD) and ulcerative colitis (UC).RESULTS: 52 patients participated in the 11 workshops divided into groups according to their diagnosis. They created a total of 1275 statements that generated 10 AxSpA concepts, 7 PsA concepts, 7 PsO concepts, 10 CD concepts and 11 UC concepts. The highest rated concepts within each disease group were: AxSpA, 'lack of understanding/to be heard and seen by healthcare professionals' (mean rating 4.0); PsA, 'medication (effects and side effects)' (mean rating 3.8); PsO, 'social and psychological problems, the shame' (mean rating 4.0); CD, 'positive attitudes' (mean rating 4.3) and UC; 'take responsibility and control over your life' (mean rating 4.0).CONCLUSION: People with SpA and associated diseases largely agree on which concepts describe their disease-related and treatment-related issues and concerns with a few of them being more disease-specific.</p

The effect of FOXA2 rs1209523 on glucose-related phenotypes and risk of type 2 diabetes in Danish individuals

<p>Abstract</p> <p>Background</p> <p>Variations within the <it>FOXA </it>family have been studied for a putative contribution to the risk of type 2 diabetes (T2D), and recently the minor T-allele of <it>FOXA2 </it>rs1209523 was reported to associate with decreased fasting plasma glucose levels in a study using a weighted false discovery rate control procedure to enhance the statistical power of genome wide association studies in detecting associations between low-frequency variants and a given trait.</p> <p>Thus, the primary aim of this study was to investigate whether the minor T-allele of rs1205923 in <it>FOXA2 </it>associated with 1) decreased fasting plasma glucose and 2) a lower risk of developing T2D. Secondly, we investigated whether rs1205923 in <it>FOXA2 </it>associated with other glucose-related phenotypes.</p> <p>Methods</p> <p>The variant was genotyped in Danish individuals from four different study populations using KASPar^®PCR SNP genotyping system. We examined for associations of the <it>FOXA2 </it>genotype with fasting plasma glucose and estimates of insulin release and insulin sensitivity following an oral glucose tolerance test in 6,162 Danish individuals from the population-based Inter99 study while association with T2D risk was assessed in 10,196 Danish individuals including four different study populations.</p> <p>Results</p> <p>The <it>FOXA2 </it>rs1209523 was not associated with fasting plasma glucose (effect size (β) = -0.03 mmol/l (95%CI: -0.07; 0.01), <it>p </it>= 0.2) in glucose-tolerant individuals from the general Danish population. Furthermore, when employing a case-control setting the variant showed no association with T2D (odds ratio (OR) = 0.82 (95%CI: 0.62-1.07), <it>p </it>= 0.1) among Danish individuals. However, when we performed the analysis in a subset of 6,022 non-obese individuals (BMI < 30 kg/m²) an association with T2D was observed (OR = 0.68 (95%CI: 0.49-0.94), <it>p </it>= 0.02). Also, several indices of insulin release and β-cell function were associated with the minor T-allele of <it>FOXA2 </it>rs1209523 in non-obese individuals.</p> <p>Conclusions</p> <p>We failed to replicate association of the minor T-allele of <it>FOXA2 </it>rs1209523 with fasting plasma glucose in a population based sample of glucose tolerant individuals. More extensive studies are needed in order to fully elucidate the potential role of <it>FOXA2 </it>in glucose homeostasis.</p

Hybrid Ytterbium-doped large-mode-area photonic crystal fiber amplifier for long wavelengths.

A large-mode-area Ytterbium-doped photonic crystal fiber amplifier with build-in gain shaping is presented. The fiber cladding consists of a hexagonal lattice of air holes, where three rows are replaced with circular high-index inclusions. Seven missing air holes define the large-mode-area core. Light confinement is achieved by combined index and bandgap guiding, which allows for single-mode operation and gain shaping through distributed spectral filtering of amplified spontaneous emission. The fiber properties are ideal for amplification in the long wavelength regime of the Ytterbium gain spectrum above 1100 nm, and red shifting of the maximum gain to 1130 nm is demonstrated

Tumor volume in subcutaneous mouse xenografts measured by microCT is more accurate and reproducible than determined by 18F-FDG-microPET or external caliper

<p>Abstract</p> <p>Background</p> <p>In animal studies tumor size is used to assess responses to anticancer therapy. Current standard for volumetric measurement of xenografted tumors is by external caliper, a method often affected by error. The aim of the present study was to evaluate if microCT gives more accurate and reproducible measures of tumor size in mice compared with caliper measurements. Furthermore, we evaluated the accuracy of tumor volume determined from ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) PET.</p> <p>Methods</p> <p>Subcutaneously implanted human breast adenocarcinoma cells in NMRI nude mice served as tumor model. Tumor volume (n = 20) was determined <it>in vivo </it>by external caliper, microCT and ¹⁸F-FDG-PET and subsequently reference volume was determined <it>ex vivo</it>. Intra-observer reproducibility of the microCT and caliper methods were determined by acquiring 10 repeated volume measurements. Volumes of a group of tumors (n = 10) were determined independently by two observers to assess inter-observer variation.</p> <p>Results</p> <p>Tumor volume measured by microCT, PET and caliper all correlated with reference volume. No significant bias of microCT measurements compared with the reference was found, whereas both PET and caliper had systematic bias compared to reference volume. Coefficients of variation for intra-observer variation were 7% and 14% for microCT and caliper measurements, respectively. Regression coefficients between observers were 0.97 for microCT and 0.91 for caliper measurements.</p> <p>Conclusion</p> <p>MicroCT was more accurate than both caliper and ¹⁸F-FDG-PET for <it>in vivo </it>volumetric measurements of subcutaneous tumors in mice.¹⁸F-FDG-PET was considered unsuitable for determination of tumor size. External caliper were inaccurate and encumbered with a significant and size dependent bias. MicroCT was also the most reproducible of the methods.</p