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 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 m 2), 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

Cellular pharmacology studies of anticancer agents: recommendations from the EORTC-PAMM group

An increasing number of manuscripts focus on the in vitro evaluation of established and novel anti-tumour agents in experimental models. Whilst the design of such in vitro assays is inherently flexible, some of these studies lack the minimum information necessary to critically evaluate their relevance or have been carried out under unsuitable conditions. The use of appropriate and robust methods and experimental design has important implications for generating results that are reliable, relevant, and reproducible. The Pharmacology and Molecular Mechanisms (PAMM) group of the European Organization for Research and Treatment of Cancer (EORTC) is the largest group of academic scientists working on drug development and bundle decades of expertise in this field. This position paper addresses all researchers with an interest in the preclinical and cellular pharmacology of anti-tumour agents and aims at generating basic recommendations for the correct use of compounds to be tested for anti-tumour activity using a range of preclinical cellular models of cancer

Sobrevivência de Salmonella enteritidis em Ovos Contaminados Artificialmente, Após Desinfecção e Armazenados em Diferentes Temperaturas Survival of Salmonella enteritidis in Eggs Artificially Contaminated, After Disinfection and Stored at Different Temperatures

Avaliou-se a contaminação da casca e do conteúdo interno de ovos inoculados com Salmonella enterica sorovar enteritidis fagotipo 4, lavados com água de torneira (AT) ou solução de amônia quaternária (AQ) e armazenados a 8ºC e 25ºC. Duzentos e cinqüenta e dois ovos foram divididos em três grupos. Os tratamentos de cada grupo consistiram de imersão em AT, AQ a 25ºC e a 43ºC. Após a secagem natural, todos os grupos foram contaminados com solução de S. enteritidis. Seguindo-se a contaminação, cada grupo tratado foi estocado a 8ºC ou 25ºC, e a presença de S. enteritidis na casca e no conteúdo interno foi avaliada após zero, 24, 96 e 168 horas. A sanitização com AQ mostrou-se eficiente na redução de S. enteritidis nas cascas dos ovos. O armazenamento dos ovos a 8ºC demonstrou ser preponderante na redução e na ausência de S. enteritidis na casca. Nos ovos lavados com AT, o armazenamento a 25ºC permitiu a permanência da bactéria nas cascas até 168 horas. Não se detectou S. enteritidis no conteúdo interno dos ovos em nenhum dos grupos.<br>The contamination of eggshell and internal content of eggs that were inoculated with Salmonella enterica serovar enteritidis phagetype 4, washed with tap water (TW) or quaternary ammonium compound (QA) and stored at 8ºC and 25ºC was evaluated. Two hundred and fifty two eggs were distributed in three groups. Each treatment of the different groups was constituted by the immersion in TW, QA at 25ºC and at 43ºC. After natural dry, all groups were infected by a S. enteritidis solution. Following the challenge, each group was stored at 8ºC or at 25ºC, and the presence of S. enteritidis in the eggshell and internal content was evaluated after zero, 24, 96 and 168 hours. The use of QA demonstrated efficiency in S. enteritidis reduction of eggshell. The eggs stored at 8ºC revealed preponderancy in the reduction and the absence of S. enteritidis at the eggshell. In the TW washed eggs, the storage at 25ºC allowed the eggshell bacteria maintenance until 168 hours. There was not any detection of S. enteritidis at the internal content of eggs in any of the groups

Data equivalence in cross-cultural international business research: assessment and guidelines

Data equivalence refers to the extent to which the elements of a research design have the same meaning, and can be applied in the same way, in different cultural contexts. Failure to establish data equivalence in cross-cultural studies may bias empirical results and theoretical inferences. Although several authors have encouraged researchers to ensure high levels of data equivalence, no study has assessed the status of the field in relation to compliance with data equivalence standards. Accordingly, this study examines three aspects of data equivalence (construct equivalence, measurement equivalence, and data collection equivalence) within 167 studies that involve cross-cultural data published in the Journal of International Business Studies, Management International Review, Journal of World Business, Strategic Management Journal and the Academy of Management Journal from 1995 to 2005. The findings indicate that international business researchers report insufficient information in relation to data equivalence issues, thus limiting confidence in the findings of many cross-cultural studies. To enhance future research, a guideline for procedures for researchers to follow and report in establishing data equivalence is offered. Journal of International Business Studies (2008) 39, 1027–1044. doi:10.1057/palgrave.jibs.8400396