19 research outputs found
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 sodiumâglucose 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 reninâangiotensin 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
Comparative potency of formulations of mometasone furoate in terms of inhibition of 'PIRHR' in the forearm skin of normal human subjects measured with laser doppler velocimetry
BACKGROUND AND AIMS: Topical glucocorticoid formulations are widely
used for effective treatment and control of a variety of dermatoses.
Mometasone furoate is a newer corticoid that has high potency but low
systemic toxicity. Pharmaceutical factors are known to significantly
influence potency and systemic absorption of topically applied
glucocorticoids. We studied the potency of "Elocon", a topical
formulation of mometasone furoate, compared with two other branded
formulations of the same corticoid. METHODS: Corticoid potency was
measured by employing a pharmacodynamic parameter of an inhibitory
effect of the corticoid on post-ischemic-reactive-hyperemic-response
(PIRHR) in human forearm skin under occlusive dressing. The PIRHR was
expressed in terms of % increase in the skin blood flow (SBF) as
measured with laser doppler velocimetry (LDV). RESULTS : All three
active branded formulations of mometasone furoate produced significant
inhibition of PIRHR. The AUC (0-2min) of PIRHR was ( Mean ± SEM ),
Control = 213.52 ± 11.80, Placebo = 209.77 ± 19.31,
Formulation A = 119.83 ± 13.71, Formulation C = 53.67 ± 4.85
and Formulation D = 111.46 ± 22.87. Formulation "C" exhibited
significantly higher topical anti-inflammatory potency than
formulations "A" or "D". CONCLUSIONS: Thus, branded formulations of the
same glucocorticoid, mometasone furoate significantly differed in their
topical anti-inflammatory potency. "Elocon" was significantly more
potent than the two other branded formulations studied
Clinical trial publication trends within neurology
Timely dissemination of results from clinical studies is crucial for the advancement of knowledge and clinical decision making. A large body of research has shown that up to half of clinical trials do not publish their findings. In this study, we sought to determine whether clinical trial publication rates within neurology have increased over time. Focusing on neurology clinical trials completed between 2008 to 2014, we found that while the overall percentage of published trials has not changed (remaining at approximately 50%), time to publication has significantly decreased. Our findings suggest that clinical trials within neurology are being published in a more timely manner