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

The application of social semiotic theory to visual elements within corporate positioning material with a view to the development of methodologies for commercial use

A thesis submitted in partial fulfilment of the requirements of the University of Wolverhampton for the degree of Doctor of PhilosophyThis worl< employs a variety of social semiotic and critical discourse techniques to develop methodologies that will assess the extent to which external positioning requirements of commercial organisations are expressed accurately in the visual imagery of their corporate artefacts. The automotive manufacturer The Rover Group was chosen to test the assessment through visual analysis of three brochures published by the company during the period 1995-97. The meanings expressed visually in the brochures were compared with the communications requirements of the Board of Directors of the Group. For the enquiry a series of templates were developed which were informed, inter alia, by concepts expressed by Kress and van Leeuwen in their work Reading Images: The Grammar of Visual Design (1996). My analysis suggests significant discrepancies occur between the positioning messages intended by the board of directors for projection externally and their expression in visual terms within the company's corporate literature. The thesis identifies where these disjunctures occur and suggests methodological templates for use by communications practitioners not trained in semiotic theory or critical discourse analysis to reduce the level of subjectivity in their analysis. The Rover Group was chosen for testing the templates because changes in ownership and structure of the company enabled me to use what would have been commercially sensitive material if the company had remained unchanged

Which Governments Come Out Ahead?

Party capability theory assumes that governments, due to their immense resources and status as repeat players, hold a great advantage over individuals and organizations pursuing litigation in courts. Less known is whether all levels of government enjoy this advantage, how they fare against one another and how an institutional arrangement such as federalism complicates such relationships. These questions are investigated using decisions made by the high courts of Australia, Canada, and the United States. The descriptive findings indicate that institutional arrangements, such as federalism, in some ways, confirm and in others confound traditional notions of which governments come out ahead, which yields important implications for party capability theory, specifically, and federalism, generally