Development and potential role of type-2 sodium-glucose transporter inhibitors for management of type 2 diabetes

There is a recognized need for new treatment options for type 2 diabetes mellitus (T2DM). Recovery of glucose from the glomerular filtrate represents an important mechanism in maintaining glucose homeostasis and represents a novel target for the management of T2DM. Recovery of glucose from the glomerular filtrate is executed principally by the type 2 sodium-glucose cotransporter (SGLT2). Inhibition of SGLT2 promotes glucose excretion and normalizes glycemia in animal models. First reports of specifically designed SGLT2 inhibitors began to appear in the second half of the 1990s. Several candidate SGLT2 inhibitors are currently under development, with four in the later stages of clinical testing. The safety profile of SGLT2 inhibitors is expected to be good, as their target is a highly specific membrane transporter expressed almost exclusively within the renal tubules. One safety concern is that of glycosuria, which could predispose patients to increased urinary tract infections. So far the reported safety profile of SGLT2 inhibitors in clinical studies appears to confirm that the class is well tolerated. Where SGLT2 inhibitors will fit in the current cascade of treatments for T2DM has yet to be established. The expected favorable safety profile and insulin-independent mechanism of action appear to support their use in combination with other antidiabetic drugs. Promotion of glucose excretion introduces the opportunity to clear calories (80–90 g [300–400 calories] of glucose per day) in patients that are generally overweight, and is expected to work synergistically with weight reduction programs. Experience will most likely lead to better understanding of which patients are likely to respond best to SGLT2 inhibitors, and under what circumstances

Sleep characteristics across the lifespan in 1.1 million people from the Netherlands, United Kingdom and United States: a systematic review and meta-analysis

How long does the average person sleep? Here, Kocevska et al. conducted a meta-analysis including over 1.1 million people to produce age- and sex-specific population reference charts for sleep duration and efficiency.We aimed to obtain reliable reference charts for sleep duration, estimate the prevalence of sleep complaints across the lifespan and identify risk indicators of poor sleep. Studies were identified through systematic literature search in Embase, Medline and Web of Science (9 August 2019) and through personal contacts. Eligible studies had to be published between 2000 and 2017 with data on sleep assessed with questionnaires including >= 100 participants from the general population. We assembled individual participant data from 200,358 people (aged 1-100 years, 55% female) from 36 studies from the Netherlands, 471,759 people (40-69 years, 55.5% female) from the United Kingdom and 409,617 people (>= 18 years, 55.8% female) from the United States. One in four people slept less than age-specific recommendations, but only 5.8% slept outside of the 'acceptable' sleep duration. Among teenagers, 51.5% reported total sleep times (TST) of less than the recommended 8-10 h and 18% report daytime sleepiness. In adults (>= 18 years), poor sleep quality (13.3%) and insomnia symptoms (9.6-19.4%) were more prevalent than short sleep duration (6.5% with TST = 9 h in bed, whereas poor sleep quality was more frequent in those spending = 41 years) reported sleeping shorter times or slightly less efficiently than men, whereas with actigraphy they were estimated to sleep longer and more efficiently than man. This study provides age- and sex-specific population reference charts for sleep duration and efficiency which can help guide personalized advice on sleep length and preventive practices.Pathophysiology, epidemiology and therapy of agein

A cost-benefit assessment of Salmonella-control strategies in pigs reared in the United Kingdom

Pork and pork products are a major source of human salmonellosis in the United Kingdom (UK). Despite a number of surveillance programmes, the prevalence of Salmonella in the UK slaughter pig population remains over 20%. Here, we present the results of a Cost-Benefit Analysis comparing five on-farm control strategies (where the cost is the cost of implementation and the benefits are the financial savings for both the human health and pig industries). The interventions considered were: wet feed, organic acids in feed, vaccination, enhanced cleaning and disinfection and movement of outdoor breeding units. The data originate from published papers and recent UK studies. The effectiveness was assessed by adapting a previous risk assessment, originally developed for the European Food Safety Authority. Using this method, none of the intervention strategies produced a net cost-benefit. Our results suggest that the cost of implementation outweighed the savings for all interventions, even if the effectiveness could be improved. Therefore, to achieve a net cost-benefit it is essential to reduce the cost of interventions. Analyses concluded that large cost reductions (up to 96%) would be required. Use of organic acids required the smallest reduction in cost (22.7%) to achieve a net cost benefit. Uncertainty analysis suggested that a small net gain might be possible, for some of the intervention measures. But this would imply that the model greatly underestimated some key parameters, which was considered unlikely. Areas of key uncertainty were identified as the under-reporting factor (i.e. the proportion of community cases of Salmonella) and the source attribution factor (i.e. the proportion of human Salmonella cases attributable to pork products)

A cost-benefit assessment of Salmonella-control strategies in pigs reared in the United Kingdom

Pork and pork products are a major source of human salmonellosis in the United Kingdom (UK). Despite a number of surveillance programmes, the prevalence of Salmonella in the UK slaughter pig population remains over 20%. Here, we present the results of a Cost-Benefit Analysis comparing five on-farm control strategies (where the cost is the cost of implementation and the benefits are the financial savings for both the human health and pig industries). The interventions considered were: wet feed, organic acids in feed, vaccination, enhanced cleaning and disinfection and movement of outdoor breeding units. The data originate from published papers and recent UK studies. The effectiveness was assessed by adapting a previous risk assessment, originally developed for the European Food Safety Authority. Using this method, none of the intervention strategies produced a net cost-benefit. Our results suggest that the cost of implementation outweighed the savings for all interventions, even if the effectiveness could be improved. Therefore, to achieve a net cost-benefit it is essential to reduce the cost of interventions. Analyses concluded that large cost reductions (up to 96%) would be required. Use of organic acids required the smallest reduction in cost (22.7%) to achieve a net cost benefit. Uncertainty analysis suggested that a small net gain might be possible, for some of the intervention measures. But this would imply that the model greatly underestimated some key parameters, which was considered unlikely. Areas of key uncertainty were identified as the under-reporting factor (i.e. the proportion of community cases of Salmonella) and the source attribution factor (i.e. the proportion of human Salmonella cases attributable to pork products)