Assessment and Management of Hypertension among Patients on Peritoneal Dialysis

Approximately 7%-10% of patients with ESKD worldwide undergo peritoneal dialysis (PD) as kidney replacement therapy. The continuous nature of this dialytic modality and the absence of acute shifts in pressure and volume parameters is an important differentiation between PD and in-center hemodialysis. However, the burden of hypertension and prognostic association of BP with mortality follow comparable patterns in both modalities. Although management of hypertension uses similar therapeutic principles, long-term preservation of residual diuresis and longevity of peritoneal membrane function require particular attention in the prescription of the appropriate dialysis regimen among those on PD. Dietary sodium restriction, appropriate use of icodextrin, and limited exposure of peritoneal membrane to bioincompatible solutions, as well as adaptation of the PD regimen to the peritoneal transport characteristics, are first-line therapeutic strategies to achieve adequate volume control with a potential long-term benefit on technique survival. Antihypertensive drug therapy is a second-line therapeutic approach, used when BP remains unresponsive to the above volume management strategies. In this article, we review the available evidence on epidemiology, diagnosis, and treatment of hypertension among patients on PD and discuss similarities and differences between PD and in-center hemodialysis. We conclude with a call for randomized trials aiming to elucidate several areas of uncertainty in management of hypertension in the PD population

A general BRST approach to string theories with zeta function regularizations

We propose a new general BRST approach to string and string-like theories which have a wider range of applicability than e g the conventional conformal field theory method. The method involves a simple general regularization of all basic commutators which makes all divergent sums to be expressible in terms of zeta functions from which finite values then may be extracted in a rigorous manner. The method is particular useful in order to investigate possible state space representations to a given model. The method is applied to three string models: The ordinary bosonic string, the tensionless string and the conformal tensionless string. We also investigate different state spaces for these models. The tensionless string models are treated in details. Although we mostly rederive known results they appear in a new fashion which deepens our understanding of these models. Furthermore, we believe that our treatment is more rigorous than most of the previous ones. In the case of the conformal tensionless string we find a new solution for d=4.Comment: 21 pages,Latexfile,revised presentation, previous title:"Critical dimensions and zeta regularizations in string theories

A proposed framework of an interactive semi-virtual environment for enhanced education of children with autism spectrum disorders

Education of people with special needs has recently been considered as a key element in the field of medical education. Recent development in the area of information and communication technologies may enable development of collaborative interactive environments which facilitate early stage education and provide specialists with robust tools indicating the person's autism spectrum disorder level. Towards the goal of establishing an enhanced learning environment for children with autism this paper attempts to provide a framework of a semi-controlled real-world environment used for the daily education of an autistic person according to the scenarios selected by the specialists. The proposed framework employs both real-world objects and virtual environments equipped with humanoids able to provide emotional feedback and to demonstrate empathy. Potential examples and usage scenarios for such environments are also described

Con: Nutritional vitaminDreplacement in chronic kidney disease and end-stage renal disease

Insufficiency of 25-hydroxyvitamin D [25(OH)D] is highly prevalent among patients with chronic kidney disease (CKD) or end-stage renal disease (ESRD) and is a critical component in the pathogenesis of secondary hyperparathyroidism. Accordingly, current National Kidney Foundation—Kidney Disease Outcomes Quality Initiative and Kidney Disease: Improving Global Outcomes guidelines recommend the correction of hypovitaminosis D through nutritional vitamin D replacement as a first-step therapeutic approach targeting secondary hyperparathyroidism. In this Polar Views debate, we summarize the existing evidence, aiming to defend the position that nutritional vitamin D replacement is not evidence-based and should not be applied to patients with CKD. This position is supported by the following: (i) our meta-analysis of randomized controlled trials shows that whereas nutritional vitamin D significantly increases serum 25(OH)D levels relative to placebo, there is no evidence either in predialysis CKD or in ESRD that parathyroid hormone (PTH) is lowered; (ii) on the other hand, in randomized head-to-head comparisons, nutritional vitamin D is shown to be inferior to activated vitamin D analogs in reducing PTH levels; (iii) nutritional vitamin D is reported to exert minimal to no beneficial actions in a series of surrogate risk factors, including aortic stiffness, left ventricular mass index (LVMI), epoetin utilization and immune function among others; and (iv) there is no evidence to support a benefit of nutritional vitamin D on survival and other ‘hard’ clinical outcomes. Whereas nutritional vitamin D replacement may restore 25(OH)D concentration to near normal, the real target of treating vitamin D insufficiency is to treat secondary hyperparathyroidism, which is untouched by nutritional vitamin D. Furthermore, the pleotropic benefits of nutritional vitamin D remain to be proven. Thus, there is little, if any, benefit of nutritional vitamin D replacement in CKD

Using affective avatars and rich multimedia content for education of children with autism

Autism is a communication disorder that mandates early and continuous educational interventions on various levels like the everyday social, communication and reasoning skills. Computer-aided education has recently been considered as a likely intervention method for such cases, and therefore different systems have been proposed and developed worldwide. In more recent years, affective computing applications for the aforementioned interventions have also been proposed to shed light on this problem. In this paper, we examine the technological and educational needs of affective interventions for autistic persons. Enabling affective technologies are visited and a number of possible exploitation scenarios are illustrated. Emphasis is placed in covering the continuous and long term needs of autistic persons by unobtrusive and ubiquitous technologies with the engagement of an affective speaking avatar. A personalised prototype system facilitating these scenarios is described. In addition the feedback from educators for autistic persons is provided for the system in terms of its usefulness, efficiency and the envisaged reaction of the autistic persons, collected by means of an anonymous questionnaire. Results illustrate the clear potential of this effort in facilitating a very promising autism intervention

Blood pressure in hemodialysis: targets?

Purpose of review In the absence of ‘hard’ clinical-trial evidence to define optimal blood pressure (BP) targets and validate different BP measurement techniques, management of hypertension in hemodialysis is based on expert opinions. In this review, we provide a comparative evaluation of out-of-dialysis BP monitoring versus dialysis-unit BP recordings in diagnosing hypertension, guiding its management and prognosticating mortality risk. Recent findings Owing to their high variability and poor reproducibility, predialysis and postdialysis BP recordings provide inaccurate reflection of the actual BP load outside of dialysis. Contrary to the reverse association of peridialytic BP with mortality, elevated home and ambulatory BP provides a direct mortality signal. Out-of-dialysis BP monitoring, even when done in the clinic, is a reliable approach to manage hypertension in the dialysis unit. Whenever none of these measures are available, median intradialytic SBP can provide a better estimate of interdialytic BP levels compared with peridialytic BP measurements. Summary Although out-of-dialysis BP monitoring have better diagnostic accuracy and prognostic validity, randomized trials are needed to ascertain BP targets for managing hypertension in hemodialysis patients

Revisiting RAAS blockade in CKD with newer potassium-binding drugs

Among patients with proteinuric chronic kidney disease (CKD), current guideline recommendations mandate the use of agents blocking the renin angiotensin aldosterone system (RAAS) as first-line antihypertensive therapy based on randomized trials demonstrating that RAAS inhibitors are superior to other antihypertensive drug classes in slowing nephropathy progression to end-stage renal disease. However, the opportunities for adequate RAAS blockade in CKD are often limited, and an important impediment is the risk of hyperkalemia, especially when RAAS inhibitors are used in maximal doses or are combined. Accordingly, a large proportion of patients with proteinuric CKD may not have the anticipated renoprotective benefits since RAAS blockers are often discontinued due to incident hyperkalemia or are administered at suboptimal doses for fear of the development of hyperkalemia. Two newer potassium binders, patiromer and sodium zirconium cyclosilicate (ZS-9), have been shown to effectively and safely reduce serum potassium levels and maintain long-term normokalemia in CKD patients receiving background therapy with RAAS inhibitors. Whether these novel potassium-lowering therapies can overcome the barrier of hyperkalemia and enhance the tolerability of RAAS inhibitor use in proteinuric CKD awaits randomized trials

Ambulatory Blood Pressure Reduction With SGLT-2 Inhibitors: Dose-Response Meta-analysis and Comparative Evaluation With Low-Dose Hydrochlorothiazide

Objective: Sodium-glucose cotransporter (SGLT)-2 inhibitors lower clinic and ambulatory blood pressure (BP), possibly through their natriuretic action. However, it remains unclear whether this BP-lowering effect is dose dependent and different from that of low-dose hydrochlorothiazide. The purpose of this meta-analysis was to quantify the association of the dose with response of ambulatory BP to SGLT-2 inhibition and to provide comparative evaluation with low-dose hydrochlorothiazide. Research design and methods: PubMed/MEDLINE, Embase, and Cochrane database of clinical trials from inception of each database through 22 August 2018. Randomized controlled trials (RCTs) reporting treatment effects of SGLT-2 inhibitors on ambulatory BP. We extracted data on the mean difference between the active treatment and placebo groups in change from baseline (CFB) of ambulatory systolic and diastolic BP. Results: We identified seven RCTs (involving 2,381 participants) comparing SGLT-2 inhibitors with placebo. Of these, two RCTs included low-dose hydrochlorothiazide as active comparator. CFB in 24-h systolic BP between SGLT-2 inhibitor and placebo groups was -3.62 mmHg (95% CI -4.29, -2.94) and in diastolic BP was -1.70 mmHg (95% CI -2.13, -1.26). BP lowering with SGLT-2 inhibition was more potent during daytime than during nighttime. The CFB in ambulatory BP was comparable between low-dose and high-dose subgroups and was similar to that for low-dose hydrochlorothiazide. Eligible RCTs did not evaluate cardiovascular outcomes/mortality. Conclusions: This meta-analysis shows that SGLT-2 inhibitors provoke an average reduction of systolic/diastolic BP 3.62/1.70 mmHg in 24-h ambulatory BP. This BP-lowering effect remains unmodified regardless of the dose of SGLT-2 inhibitor and is comparable with BP-lowering efficacy of low-dose hydrochlorothiazide