A new perspective on metformin therapy in type 1 diabetes

Metformin is quite frequently used off-label in type 1 diabetes to limit insulin dose requirement. Guidelines recommend that it can improve glucose control in those who are overweight and obese but evidence in support of this is limited. Recently-published findings from the REducing with MetfOrmin Vascular Adverse Lesions (REMOVAL) trial suggest that metformin therapy in type 1 diabetes can reduce atherosclerosis progression, weight and LDL-cholesterol levels. This provides a new perspective on metformin therapy in type 1 diabetes and suggests a potential role for reducing the long-term risk of cardiovascular disease

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Abstract Forthcoming

Cardiovascular benefits of GLP-1 agonists in type 2 diabetes: a comparative review

Type 2 diabetes (T2D) carries risks of both cardiovascular (CV) (myocardial infarction, stroke, and peripheral vascular disease) and microvascular (retinopathy/nephropathy/neuropathy) complications. Glucose-lowering is an effective strategy for preventing microvascular complications, but the extent to which it can reduce CV complications is less certain. Glucagon-like peptide-1 (GLP-1) agonists are potent glucose-lowering agents but also have potentially beneficial effects on other traditional (body weight, blood pressure (BP), and LDL cholesterol) and non-traditional risk factors (low grade inflammation and endothelial dysfunction). The results of four large CV outcome trials with GLP-1 agonists are now available. These have compared lixisenatide (ELIXA), liraglutide (LEADER), semaglutide (SUSTAIN-6), and long-acting exenatide (EXSCEL) with placebo and standard of care over 2–4 years; four others (including with dulaglutide and albiglutide) are ongoing. LEADER and SUSTAIN-6 have demonstrated reductions in rates of major adverse CV events with active GLP-1 treatment but ELIXA and EXSCEL have not. In this review, we discuss the mechanisms by which GLP-1 receptor agonists act on the CV system and the design and conduct of these trials. Contrary to the assertions that (a) all GLP-1 agonists reduce CV disease in T2D but to different extents or (b) the magnitude of CV protection is predominantly related to glucose-lowering, we argue that CV benefit is specific to agents that provide longer acting agonism at the GLP-1 receptor. The mechanisms involve reduction in body weight and BP, and lowering of LDL-cholesterol and glucose, but pleiotropic effects—including suppression of low grade inflammation, vasodilation, and natriuresis—are also likely relevant

Intra-session and inter-day reliability of the Myon 320 electromyography system during sub-maximal contractions

Electromyography systems are widely used within the field of scientific and clinical practices. The reliability of these systems are paramount when conducting research. The reliability of Myon 320 Surface Electromyography System is yet to be determined. This study aims to determine the intra-session and inter-day reliability of the Myon 320 Surface Electromyography System. Muscle activity from fifteen participants was measured at the anterior deltoid muscle during a bilateral front raise exercise, the vastus lateralis muscle during a squat exercise and the extensor carpi radialis brevis (ECRB) muscle during an isometric handgrip task. Intra-session and inter-day reliability was calculated by intraclass correlation coefficient, standard error of measurement and coefficient of variation (CV). The normalized root mean squared (RMS) surface electromyographic signals produced good intra-session and inter-day testing intraclass correlation coefficient values (range: 0.63-0.97) together with low standard error of measurement (range: 1.49-2.32) and CV (range: 95% Confidence Interval = 0.36-12.71) measures for the dynamic-and-isometric contractions. The findings indicate that the Myon 320 Surface Electromyography System produces good to fair reliability when examining intra-session and inter-day reliability. Findings of the study provide evidence of the reliability of electromyography between trials which is essential during clinical testing.</p

(4-Hydr­oxy-3-nitro­benz­yl)methyl­ammonium chloride

The title compound, C8H11N2O3 +·Cl−, was synthesized as an inter­mediate in the development of a new sugar sensor. The structure displays N—H⋯Cl and O—H⋯O hydrogen bonding, as well as weak O—H⋯Cl inter­actions and π–π stacking (3.298 Å). There are two formula units in the asymmetric unit

Recent developments in adjunct therapies for type 1 diabetes

Introduction: There have been many recent advances in the treatment of type 1 diabetes (T1D) including in insulin formulations, continuous glucose monitoring (CGM) technology and automated insulin delivery. However, long-term optimal glycemic control is still only achieved in a minority. Areas covered: Adjunct therapy – the use of therapeutic agents other than insulin – is one strategy aimed at improving outcomes. An ideal adjunct agent would improve glycemic control, reduce weight (or weight gain), reduce insulin requirement and prevent complications (e.g. cardiorenal) without increasing hypoglycemia. The amylin analogue pramlintide has been licensed in the USA, while the sodium glucose co-transporter-2 inhibitor (SGLT2i) dapagliflozin, was briefly (2019 − 2021) licensed for type 1 diabetes in Europe and the UK. However, other agents from the type 2 diabetes (T2D) arena including metformin, other SGLT2is, glucagon-like peptide-1 receptor agonists (GLP-1RA) and dipeptidyl peptidase-IV (DPP-4) inhibitors have been investigated. Expert opinion: As evidence emerges for cardiorenal protection by SGLT2is and GLP-1RAs in T2D, it has become increasingly important to know whether people with T1D can also benefit. Here, we review recent trials of adjunct agents in T1D and discuss the efficacy and safety of these agents (alone and in combination) in an era in which continuous glucose monitoring is becoming standard of care

Improving the quality of weekend medical handover on non-receiving medical hospital wards

INTRODUCTION: Handover is the system by which the responsibility for immediate and ongoing care is transferred between healthcare professionals and can be an area of risk. The Royal College of Physicians (RCP) has recommended improvement and standardisation of handover. Locally, national training surveys have reported poor feedback regarding handover at Glasgow Royal Infirmary. AIM: To improve and standardise handover from weekday to weekend teams. METHODS: The Plan–Do–Study–Act (PDSA) quality improvement framework was used. Interventions were derived from a driver diagram after consultation with relevant stakeholders. Four PDSA cycles were completed over a 4-month period: PDSA cycle 1—Introduction of standardised paper form on three wards. PDSA cycle 2—Introduction of electronic handover system on three wards. PDSA cycle 3—Expansion of electronic handover to seven wards. PDSA cycle 4—Expansion of electronic handover to all non-receiving medical wards. The outcome of interest was the percentage of patients with full information handed over based on a six-point scale derived from the RCP. Data were collected weekly throughout the study period. RESULTS: 18 data collection exercises were performed including 525 patients. During the initial phase there was an improvement in handover quality with 0/28 (0%) at baseline having all six points completed compared with 13/48 (27%) with standardised paper form and 21/42 (50%) with the electronic system (p<0.001). When the electronic handover form was expanded to all wards, the increased quality was maintained, however, to a lesser extent compared with the initial wards. CONCLUSION: A standardised electronic handover system was successfully introduced to downstream medical wards over a short time period. This led to an in improvement in the quality of handover in the initial wards involved. When expanded to a greater number of wards there was still an improvement in quality but to a lesser degree

Detection of ctDNA from dried blood spots after DNA size selection

Background: Recent advances in the study and clinical applications of circulating tumor DNA (ctDNA) are limited by practical considerations of sample collection. Whole genome sequencing (WGS) is increasingly used for analysis of ctDNA, identifying copy-number alterations and fragmentation patterns. We hypothesized that low-depth/shallow WGS (sWGS) data may be generated from minute amounts of cell-free DNA, and that fragment-size selection may remove contaminating genomic DNA from small blood volumes. Dried blood spots have practical advantages for sample collection, may facilitate serial sampling, and could support novel study designs in humans and animal models. Methods: We developed a protocol for the isolation and analysis of cell-free DNA from dried blood spots using filter paper cards and bead-based size selection. DNA extracted and size-selected from dried spots was analyzed using sWGS and PCR. Results: Analyzing a 50L dried blood spot from frozen whole blood of a patient with melanoma, we identified ctDNA based on the presence of tumor-specific somatic copy-number alterations, and found a fragment size profile similar to that observed in plasma DNA. We found alterations in different chromosomes in blood-spots from two patients with high-grade serous ovarian carcinoma. Extending this approach to serial dried blood spots from mouse xenograft models, we detect tumor-derived cell-free DNA and identified ctDNA from the originally grafted ascites. Conclusion: Our data suggest that ctDNA can be detected and monitored in dried blood spots from archived and fresh blood samples, enabling new approaches for sample collection and novel study/trial designs for both patients and in vivo models.The University of Cambridge and Cancer Research UK (grant numbers A20240 and A29580). The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement n.337905. Healthy volunteer samples were provided by the Cambridge Blood and Stem Cell Biobank, which is supported by the Cambridge NIHR Biomedical Research Centre, Wellcome Trust - MRC Stem Cell Institute and the Cambridge Experimental Cancer Medicine Centre, UK

Faint AGN and the Ionizing Background

We determine the evolution of the faint, high-redshift, optical luminosity function (LF) of AGN implied by several observationally-motivated models of the ionizing background. Our results depend crucially on whether we use the total ionizing rate measured by the proximity effect technique or the lower determination from the flux decrement distribution of Ly alpha forest lines. Assuming a faint-end LF slope of 1.58 and the SDSS estimates of the bright-end slope and normalization, we find that the LF must break at M_B*=-24.2,-22.3, -20.8 at z=3,4, 5 if we adopt the lower ionization rate and assume no stellar contribution to the background. The break must occur at M_B*=-20.6,-18.7, -18.7 for the proximity effect background estimate. These values brighten by as much as ~2 mag if high-z galaxies contribute to the background with an escape fraction of ionizing photons consistent with recent estimates: f_e=0.16. By comparing to faint AGN searches, we find that the typically-quoted proximity effect estimates of the background imply an over-abundance of faint AGN (even with f_e=1). Even adopting the lower bound on proximity effect measurements, the stellar escape fraction must be high: f_e>0.2. Conversely, the lower flux- decrement-derived background requires a limited stellar contribution: f_e<0.05. Our derived LFs together with the locally-estimated black hole density suggest that the efficiency of converting mass to light in optically-unobscured AGN is somewhat lower than expected, <0.05. Comparison with similar estimates based on X-ray counts suggests that more than half of all AGN are obscured in the UV/optical. We also derive lower limits on typical AGN lifetimes and obtain >10^7 yrs for favored cases.Comment: 19 pages, 16 figures. Accepted by Astrophysical Journa

Health screening, cardiometabolic disease and adverse health outcomes in individuals with severe mental illness

Background: Poor physical health in severe mental illness (SMI) remains a major issue for clinical practice. Aims: To use electronic health records of routinely collected clinical data to determine levels of screening for cardiometabolic disease and adverse health outcomes in a large sample (n = 7718) of patients with SMI, predominantly schizophrenia and bipolar disorder. Method: We linked data from the Glasgow Psychosis Clinical Information System (PsyCIS) to morbidity records, routine blood results and prescribing data. Results: There was no record of routine blood monitoring during the preceding 2 years for 16.9% of the cohort. However, monitoring was poorer for male patients, younger patients aged 16–44, those with schizophrenia, and for tests of cholesterol, triglyceride and glycosylated haemoglobin. We estimated that 8.0% of participants had diabetes and that lipids levels, and use of lipid-lowering medication, was generally high. Conclusions: Electronic record linkage identified poor health screening and adverse health outcomes in this vulnerable patient group. This approach can inform the design of future interventions and health policy