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.
Batrachochytrium dendrobatidis is a fungus belonging to the Phylum Chytridiomycota, Class Chytridiomycetes, Order Chytridiales, and is the highly infectious aetiological agent responsible for a ...potentially fatal disease, chytridiomycosis, which is currently decimating many of the world's amphibian populations. The fungus infects 2 amphibian orders (Anura and Caudata), 14 families and at least 200 species and is responsible for at least 1 species extinction. Whilst the origin of the agent and routes of transmission are being debated, it has been recognised that successful management of the disease will require effective sampling regimes and detection assays. We have developed a range of unique sampling protocols together with diagnostic assays for the detection of B. dendrobatidis in both living and deceased tadpoles and adults. Here, we formally present our data and discuss them in respect to assay sensitivity, specificity, repeatability and reproducibility. We suggest that compliance with the recommended protocols will avoid the generation of spurious results, thereby providing the international scientific and regulatory community with a set of validated procedures which will assist in the successful management of chytridiomycosis in the future.
Batrachochytrium dendrobatidis is a major pathogen of frogs worldwide, associated with declines in amphibian populations. Diagnosis of chytridiomycosis to date has largely relied upon histological ...and immunohistochemical examination of toe clips. This technique is invasive and insensitive particularly at early stages of infection when treatment may be possible. We have developed a real-time PCR Taqman assay that can accurately detect and quantify one zoospore in a diagnostic sample. This assay will assist the early detection of B. dendrobatidis in both captive and wild populations, with a high degree of sensitivity and specificity, thus facilitating treatment and protection of endangered populations, monitoring of pristine environments and preventing further global spread via amphibian trade.
The introduction of the Mayo End‐Stage Liver Disease score into the Organ Procurement and Transplantation Network (OPTN) deceased donor liver allocation policy in 2002 has led to a significant ...increase in the number of simultaneous liver–kidney transplants in the United States. Despite multiple attempts, clinical science has not been able to reliably predict which liver candidates with renal insufficiency will recover renal function or need a concurrent kidney transplant. The problem facing the transplant community is that currently there are almost no medical criteria for candidacy for simultaneous liver–kidney allocation in the United States, and this lack of standardized rules and medical eligibility criteria for kidney allocation with a liver is counter to OPTN's Final Rule. Moreover, almost 50% of simultaneous liver–kidney organs come from a donor with a kidney donor profile index of ≤0.35. The kidneys from these donors could otherwise be allocated to pediatric recipients, young adults or prior organ donors. This paper presents the new OPTN and United Network of Organ Sharing simultaneous liver–kidney allocation policy, provides the supporting evidence and explains the rationale on which the policy was based.
Simultaneous liver–kidney transplantation occurs without any standardized medical eligibility criteria, and the authors present a policy, developed by a committee representing a diverse group of transplant professionals, intended to bring order to this otherwise chaotic system.
OPTN/SRTR 2013 Annual Data Report: Kidney Matas, A. J.; Smith, J. M.; Skeans, M. A. ...
American journal of transplantation,
January 2015, 2015-Jan, 2015-01-00, 20150101, Letnik:
15, Številka:
S2
Journal Article
Recenzirano
ABSTRACT
A new kidney allocation system, expected to be implemented in late 2014, will characterize donors on a percent scale (0%‐100%) using the kidney donor profile index (KDPI). The 20% of ...deceased donor kidneys with the greatest expected posttransplant longevity will be allocated first to the 20% of candidates with the best expected posttransplant survival; kidneys that are not accepted will then be offered to remaining 80% of candidates. Waiting time will start at the time of maintenance dialysis initiation (even if before listing) or at the time of listing with an estimated glomerular filtration rate of 20 mL/min/1.73 m2 or less. Under the current system, the number of candidates on the waiting list continues to increase, as each year more candidates are added than are removed. Median waiting times for adults increased from 3 years in 2003 to more than 4.5 years in 2009. Donation rates have not increased. Short‐term outcomes continue to improve; death‐censored graft survival at 90 days posttransplant was 97% or higher for deceased donor transplants and over 99% for living donor transplants. In 2013, 883 pediatric candidates were added to the waiting list; 65.8% of pediatric candidates on the list in 2013 underwent deceased donor transplant. Five‐year graft survival was highest for living donor recipients aged younger than 11 years (89%) and lowest for deceased donor recipients aged 11 to 17 years (68%).
Rapid magnetic stimulation (RMS) of the phrenic nerves may serve to attenuate diaphragm atrophy during mechanical ventilation. With different coil shapes and stimulation location, inspiratory ...responses and side-effects may differ. This study aimed to compare the inspiratory and sensory responses of three different RMS-coils either used bilaterally on the neck or on the chest, and to determine if ventilation over 10 min can be achieved without muscle fatigue and coils overheating.
Healthy participants underwent bilateral anterior 1-s RMS on the neck (RMS
) (N = 14) with three different pairs of magnetic coils (parabolic, D-shape, butterfly) at 15, 20, 25 and 30 Hz stimulator-frequency and 20% stimulator-output with + 10% increments. The D-shape coil with individual optimal stimulation settings was then used to ventilate participants (N = 11) for up to 10 min. Anterior RMS on the chest (RMS
) (N = 8) was conducted on an optional visit. Airflow was assessed via pneumotach and transdiaphragmatic pressure via oesophageal and gastric balloon catheters. Perception of air hunger, pain, discomfort and paresthesia were measured with a numerical scale.
Inspiration was induced via RMS
in 86% of participants with all coils and via RMS
in only one participant with the parabolic coil. All coils produced similar inspiratory and sensory responses during RMS
with the butterfly coil needing higher stimulator-output, which resulted in significantly larger discomfort ratings at maximal inspiratory responses. Ten of 11 participants achieved 10 min of ventilation without decreases in minute ventilation (15.7 ± 4.6 L/min).
RMS
was more effective than RMS
and could temporarily ventilate humans seemingly without development of muscular fatigue. Trial registration This study was registered on clinicaltrials.gov (NCT04176744).
Abstract Background Near-peer teaching is a popular pedagogical teaching tool however many existing models fail to demonstrate benefits in summative OSCE performance. The 3-step deconstructed ...(3-D)skills near-peer model was recently piloted in undergraduate medicine showing short term improvement in formative OSCE performance utilising social constructivist educational principles. This study aims to assess if 3-D skills model teaching affects summative OSCE grades. Methods Seventy-nine third year medical students attended a formative OSCE event at the University of Glasgow receiving an additional 3-minutes per station of either 3-D skills teaching or time-equivalent unguided practice. Students’ summative OSCE results were compared against the year cohort to establish whether there was any difference in time delayed summative OSCE performance. Results 3-D skills and unguided practice cohorts had comparable demographical data and baseline formative OSCE performance. Both the 3-D skill cohort and unguided practice cohort achieved significantly higher median station pass rates at summative OSCEs than the rest of the year. This correlated to one additional station pass in the 3-D skills cohort, which would increase median grade banding from B to A. The improvement in the unguided practice cohort did not achieve educational significance. Conclusion Incorporating the 3-D skills model into a formative OSCE is associated with significantly improved performance at summative OSCEs. This expands on the conflicting literature for formative OSCE sessions which have shown mixed translation to summative performance and suggests merit in institutional investment to improve clinical examination skills.
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.
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.
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.
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