Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Proposal of a Clinical Decision Tree Algorithm Using Factors Associated with Severe Dengue Infection.

WHO's new classification in 2009: dengue with or without warning signs and severe dengue, has necessitated large numbers of admissions to hospitals of dengue patients which in turn has been imposing a huge economical and physical burden on many hospitals around the globe, particularly South East Asia and Malaysia where the disease has seen a rapid surge in numbers in recent years. Lack of a simple tool to differentiate mild from life threatening infection has led to unnecessary hospitalization of dengue patients.We conducted a single-centre, retrospective study involving serologically confirmed dengue fever patients, admitted in a single ward, in Hospital Kuala Lumpur, Malaysia. Data was collected for 4 months from February to May 2014. Socio demography, co-morbidity, days of illness before admission, symptoms, warning signs, vital signs and laboratory result were all recorded. Descriptive statistics was tabulated and simple and multiple logistic regression analysis was done to determine significant risk factors associated with severe dengue.657 patients with confirmed dengue were analysed, of which 59 (9.0%) had severe dengue. Overall, the commonest warning sign were vomiting (36.1%) and abdominal pain (32.1%). Previous co-morbid, vomiting, diarrhoea, pleural effusion, low systolic blood pressure, high haematocrit, low albumin and high urea were found as significant risk factors for severe dengue using simple logistic regression. However the significant risk factors for severe dengue with multiple logistic regressions were only vomiting, pleural effusion, and low systolic blood pressure. Using those 3 risk factors, we plotted an algorithm for predicting severe dengue. When compared to the classification of severe dengue based on the WHO criteria, the decision tree algorithm had a sensitivity of 0.81, specificity of 0.54, positive predictive value of 0.16 and negative predictive of 0.96.The decision tree algorithm proposed in this study showed high sensitivity and NPV in predicting patients with severe dengue that may warrant admission. This tool upon further validation study can be used to help clinicians decide on further managing a patient upon first encounter. It also will have a substantial impact on health resources as low risk patients can be managed as outpatients hence reserving the scarce hospital beds and medical resources for other patients in need

Effect of Rice (Oryza sativa L.) Ceramides Supplementation on Improving Skin Barrier Functions and Depigmentation: An Open-Label Prospective Study

Ceramides plays a crucial role in maintaining skin barrier function. Although foregoing evidence supported beneficial effects of topical ceramides for restoration of the skin barrier, studies on oral ceramides are extremely scarce, with most published data collected from in vivo and in vitro models. Thus, this study aimed to evaluate the efficacy of rice ceramides (RC) supplementation to improve skin barrier function and as a depigmenting agent through comprehensive clinical assessments. This study investigated the beneficial effects of orally administered RC supplementation in 50 voluntary participants. Skin hydration, firmness and elasticity, transepidermal water loss (TEWL), melanin index (MI), erythema index (EI), sebum production, pH, and wrinkle severity were assessed at baseline and during monthly follow-up visits. RC supplementation was found to significantly (p < 0.01) improve skin hydration, sebum production, firmness and elasticity, and wrinkle severity for three assessed areas, namely the left cheek, dorsal neck, and right inner forearm. Additionally, RC significantly (p < 0.01) reduced the rates of TEWL, levels of MI and EI. Analyses of data indicated that participants at older age were more responsive towards the effect of RC supplementation. Our findings suggest that RC supplementation can effectively improve skin barrier function, reduce wrinkle severity, and reduce pigmentation

Percentage of warning signs by dengue severity.

<p>Percentage of warning signs by dengue severity.</p

Comparison of decision tree with actual clinical diagnosis.

<p>Comparison of decision tree with actual clinical diagnosis.</p

Demographic profiles of dengue patients.

<p>Demographic profiles of dengue patients.</p

Significant factors associated with severe dengue (using multiple logistic regressions).

<p>Significant factors associated with severe dengue (using multiple logistic regressions).</p

Decision tree for severe dengue infection.

<p>Decision tree for severe dengue infection.</p

Temporal Data Dissemination in Vehicular Cyber-Physical Systems

Efficient data dissemination is one of the fundamental requirements to enable emerging applications in vehicular cyber-physical systems. In this paper, we present the first study on real-time data services via roadside-to-vehicle communication by considering both the time constraint of data dissemination and the freshness of data items. Passing vehicles can submit their requests to the server, and the server disseminates data items accordingly to serve the vehicles within its coverage. Data items maintained in the database are periodically updated to keep the information up-to-date. We present the system model and analyze challenges on data dissemination by considering both application requirements and communication characteristics. On this basis, we formulate the temporal data dissemination (TDD) problem by introducing the snapshot consistency requirement on serving real-time requests for temporal data items. We prove that TDD is NP-hard by constructing a polynomial-time reduction from the Clique problem. Based on the analysis of the time bound on serving requests, we propose a heuristic scheduling algorithm, which considers the request characteristics of productivity, status, and urgency in scheduling. An extensive performance evaluation demonstrates that the proposed algorithm is able to effectively exploit the broadcast effect, improve the bandwidth efficiency, and enhance the request service chance. © 2000-2011 IEEE.

Model-based Customer-Relationship Management System and Strategic Board Game: Analogical Training

The pandemic has caused much mental, social and financial stress. Policies and standard operating procedures have helped to alleviate some stress and create systematicity, expectancy, and predictability. This paper aims to alleviate some of the stress through model-based social customer relationship management system, an Augmented Reality board game, and two mini tourism games. The first aims to increase collaboration among stakeholders and to increase more effective and efficient resource management. The second phases players through the preparation, recruitment, attack and observation phases at a slower pace than competitive gaming. The third and fourth project introduce places and trigger memories through mini games respectively. These provide analogical training in social customer relationship management and in developing more systematic thinking, expectations, fun and mindfulness. AI-assistance would enable personalization/intelligent context-aware recommendations