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

Oral Manifestations Associated to Paracoccidioidomicosis and Histoplasmosis

Objective: To determine the frequency and clinical forms of oral manifestations associated to Paracoccidioidomycosis (PCM) and Histoplasmosis. Material and Methods: 481 medical records of outpatients referred to the Medical Mycology Department were reviewed since 2009 to 2016. Data were analyzed using descriptive statistical methods. Results: 47 (9.77%) cases had oral manifestations, 29 (61.70%) were associated to PCM and 18 (38.29%) to histoplasmosis. For PCM, male-female ratio was 8:1 and 1:1 for histoplasmosis. The average age for PCM was 48 years old and 53 for histoplasmosis. All the PCM patients had more than 1 oral structure affected: 44.82% were gingival lesions and 27.58% palate. In patients with histoplasmosis, 6 (33.33%) were lesions affecting palate and 6 (33.33%) involving tongue. For both entities, painful ulcers and granulomatous-like lesions were the most prevalent clinical forms; however, we observed a wide range of other oral manifestations. Regarding PCM patient’s comorbidities, 3 (10.34%) cases had HIV/AIDS, 8 (27.58%) histoplasmosis and 2 (6.89%) carcinomas. Whereas the comorbidities of patients with histoplasmosis, 2 (11.11%) had HIV/AIDS and 1 (5.55%) had carcinoma. Conclusion: In endemic countries for both mycoses, dentists must be aware of patients with mouth lesions, take advantage of epidemiologic clues that suggest risk factors and be acquainted with all the current diagnostic tests in order to make a quick diagnosis and treatment in highly suspicious cases

Dose-dependent effect of antipsychotic drugs on autonomic nervous system activity in schizophrenia

<p>Abstract</p> <p>Background</p> <p>Antipsychotic drugs are considered a trigger factor for autonomic dysregulation, which has been shown to predict potentially fatal arrhythmias in schizophrenia. However, the dose-dependent effect of antipsychotic drugs and other psychotropic drugs on autonomic nervous system (ANS) activity remain unclear. The purpose of this study was to investigate the dose-dependent effect of antipsychotic drugs and other clinical factors on ANS activity in an adequate sample size of patients with schizophrenia.</p> <p>Methods</p> <p>A total of 211 Japanese patients with schizophrenia and 44 healthy subjects participated in this study. ANS activity was assessed by means of heart rate variability (HRV) power spectral analysis. Antipsychotic drug treatment and various clinical factors were investigated for each participant. The patient group was categorized into three subgroups according to daily dose of antipsychotic drug, and HRV was compared between groups.</p> <p>Results</p> <p>The results showed significantly decreased low-frequency and high-frequency components of HRV in the patient group compared to the control group. The high-dose group showed a significantly lower HRV than the medium-dose group and an even lower HRV than the low-dose group. In addition, a significant association between HRV and antipsychotic drug dose was identified by multiple regression analysis. HRV was not associated with age, sex, body mass index, duration of illness, or daily dose of other psychotropic drugs.</p> <p>Conclusion</p> <p>These results suggest that antipsychotic drugs exert a significant dose-dependent effect on the extent of decline in ANS activity, and that optimal antipsychotic medication is required to avoid possible cardiovascular adverse events in patients with schizophrenia.</p