Better implementation of improvements in chronic care

We know more about the effectiveness of chronic care itself than we know about how to implement these effective practices and care models. The result of this mismatch is that too often the implementation of inherently good innovations fails. Luckily, this is recognised as a problem and we are beginning to use methods which combine implementation with research so that we can more quickly improve care and learn about what works best for whom and where. This report presents a synthesis of what a diverse group of experts across the European Union see as research priorities to speed up and spread improvements to chronic care. It will contribute to the future EU Research Agenda and also seeks to stimulate research funding for rigorous and timely implementation research in chronic care. But it is also of immediate use to improvers and researchers across Europe for the insights and discussions about implementation, chronic care and improvement science and practice

GLP-1 receptor agonists do not affect sodium intake: Exploratory analyses from two randomized clinical trials

Objectives: Excessive sodium intake, despite current dietary advice, remains a global issue with cardiovascular and renal consequences. The aim of this study was to determine whether glucagon-like peptide receptor agonists (GLP-1 RAs), used as antihyperglycemic agents for type 2 diabetes (T2DM) management, may reduce salt cravings as they are known to reduce hedonic feeding behavior and are involved in sodium homeostasis by increasing renal sodium excretion. Methods: We performed exploratory analyses using data from two randomized, clinical crossover trials, which primarily aimed to assess the effects of GLP-1 RAs on central satiety and reward circuits and subsequent related feeding behavior. In study A, healthy, obese individuals and patients with T2DM were randomly assigned to receive intravenous administration of placebo or GLP-1 RA exenatide with or without concurrent GLP-1 receptor blockade, on separate testing days. In study B, individuals with T2DM randomly received GLP-1 RA liraglutide (titrated up to 1.8 mg daily) or titrated insulin glargine for 12 wk. In both studies, participants received an ad libitum mixed meal that served to calculate sodium intake. Moreover, salt craving was scored using a Likert scale. Results: In study A, acute exenatide, parallel to reduced total food intake, reduced sodium intake in all studied groups by up to 30%. In study B, prolonged liraglutide treatment did not affect sodium or total caloric intake. Neither acute exenatide nor prolonged liraglutide treatment affected salt craving as measured by the Likert scale. Conclusion: Acute exenatide reduced sodium intake in light of a generalized reduction in food ingestion, while prolonged intervention with liraglutide did not lower sodium intake. Neither intervention affected salt craving. Given the known effects of these drugs on renal sodium excretion, blood pressure, and renal and cardiovascular outcome, it seems plausible to perform dedicated mechanistic studies in humans to assess the effects of GLP-1 RA administration on sodium balance

GLP-1 and the kidney : from physiology to pharmacology and outcomes in diabetes

The gastrointestinal tract - the largest endocrine network in human physiology - orchestrates signals from the external environment to maintain neural and hormonal control of homeostasis. Advances in understanding entero-endocrine cell biology in health and disease have important translational relevance. The gut-derived incretin hormone glucagon-like peptide 1 (GLP-1) is secreted upon meal ingestion and controls glucose metabolism by modulating pancreatic islet cell function, food intake and gastrointestinal motility, amongst other effects. The observation that the insulinotropic actions of GLP-1 are reduced in type 2 diabetes mellitus (T2DM) led to the development of incretin-based therapies - GLP-1 receptor agonists and dipeptidyl peptidase 4 (DPP-4) inhibitors - for the treatment of hyperglycaemia in these patients. Considerable interest exists in identifying effects of these drugs beyond glucose-lowering, possibly resulting in improved macrovascular and microvascular outcomes, including in diabetic kidney disease. As GLP-1 has been implicated as a mediator in the putative gut-renal axis (a rapid-acting feed-forward loop that regulates postprandial fluid and electrolyte homeostasis), direct actions on the kidney have been proposed. Here, we review the role of GLP-1 and the actions of associated therapies on glucose metabolism, the gut-renal axis, classical renal risk factors, and renal end points in randomized controlled trials of GLP-1 receptor agonists and DPP-4 inhibitors in patients with T2DM

Predictive Factors and Risk Model for Positive Circumferential Resection Margin Rate after Transanal Total Mesorectal Excision in 2653 Patients with Rectal Cancer

The aim of this study was to determine the incidence of, and preoperative risk factors for, positive circumferential resection margin (CRM) after transanal total mesorectal excision (TaTME). Background: TaTME has the potential to further reduce the rate of positive CRM for patients with low rectal cancer, thereby improving oncological outcome. Methods: A prospective registry-based study including all cases recorded on the international TaTME registry between July 2014 and January 2018 was performed. Endpoints were the incidence of, and predictive factors for, positive CRM. Univariate and multivariate logistic regressions were performed, and factors for positive CRM were then assessed by formulating a predictive model. Results: In total, 2653 patients undergoing TaTME for rectal cancer were included. The incidence of positive CRM was 107 (4.0%). In multivariate logistic regression analysis, a positive CRM after TaTME was significantly associated with tumors located up to 1 cm from the anorectal junction, anterior tumors, cT4 tumors, extra-mural venous invasion (EMVI), and threatened or involved CRM on baseline MRI (odds ratios 2.09, 1.66, 1.93, 1.94, and 1.72, respectively). The predictive model showed adequate discrimination (area under the receiver-operating characteristic curve >0.70), and predicted a 28% risk of positive CRM if all risk factors were present. Conclusion: Five preoperative tumor-related characteristics had an adverse effect on CRM involvement after TaTME. The predicted risk of positive CRM after TaTME for a specific patient can be calculated preoperatively with the proposed model and may help guide patient selection for optimal treatment and enhance a tailored treatment approach to further optimize oncological outcomes