Long-term efficacy and safety of ertugliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin monotherapy: 104-week VERTIS MET trial.

AIM: To evaluate the long-term efficacy and safety of ertugliflozin in adults with type 2 diabetes mellitus inadequately controlled on metformin. MATERIALS AND METHODS: A 104-week Phase III, randomized double-blind study with a 26-week placebo-controlled period (Phase A) and a 78-week period (Phase B) where blinded glimepiride was added to non-rescued placebo participants with fasting fingerstick glucose ≥6.1 mmol/L. Results through week 104 are reported. RESULTS: Mean (standard error) change in HbA1c from baseline was -0.7% (0.07) and -1.0% (0.07) at week 52; -0.6% (0.08) and -0.9% (0.08) at week 104 for ertugliflozin 5 and 15 mg. At week 52, 34.8% and 36.6% participants had HbA1c <7.0%, and 24.6% and 33.7% at week 104, for ertugliflozin 5 and 15 mg. Ertugliflozin reduced fasting plasma glucose (FPG), body weight and systolic blood pressure (SBP) from baseline through week 104. The incidence of female genital mycotic infections (GMIs) was higher with ertugliflozin, and symptomatic hypoglycaemia was lower for ertugliflozin versus placebo/glimepiride. Minimal bone mineral density (BMD) changes were observed, similar to placebo/glimepiride, except at total hip where reduction in BMD was greater with ertugliflozin 15 mg versus placebo/glimepiride: difference in least squares means (95% CI) -0.50% (-0.95, -0.04) at week 52 and -0.84% (-1.44, -0.24) at week 104. CONCLUSIONS: Ertugliflozin maintained improvements from baseline in HbA1c, FPG, body weight and SBP through week 104. Ertugliflozin was well tolerated, with non-clinically relevant changes in BMD. Compared with placebo/glimepiride, ertugliflozin increased female GMIs, but reduced the incidence of symptomatic hypoglycaemia. ClinicalTrials.gov Identifier: NCT02033889.

Vulvovaginal pyoderma gangrenosum secondary to rituximab therapy.

Rituximab is being used increasingly for the treatment of B-cell malignancies and nonmalignant conditions. Pyoderma gangrenosum is a rare neutrophilic dermatosis, which can be either idiopathic or associated with underlying systemic inflammatory conditions. We present a series of 4 patients who presented with ulcerative pyoderma gangrenosum in the vulvovaginal area after treatment with rituximab.

Severe vulvovaginitis associated with intravaginal nystatin therapy.

A 64-year-old woman had severe vulvovaginitis develop while she was receiving intravaginal nystatin therapy for Candida glabrata infection. Mucocutaneous adverse effects have rarely been reported with nystatin despite long years of use. This complication should be included in the differential diagnosis of clinical failure of intravaginal nystatin therapy.

Randomised double-blind study of norfloxacin and cefadroxil in the treatment of acute pyelonephritis.

In a coordinated, double-blind multi-centre trial, adults with symptoms of acute pyelonephritis were randomly assigned to receive a two-week course of oral treatment with either 400 mg norfloxacin twice daily or 1 g cefadroxil twice daily. Of 197 patients enrolled in the study, 140 could be evaluated for drug efficacy and 193 for drug safety. Norfloxacin gave a significantly higher bacteriological cure rate than cefadroxil, both at 3 to 10 days (98% versus 65%; p less than 0.0001; 95% confidence interval (CI) for difference in proportions 21-46%) and up to eight weeks (87% versus 48%; p less than 0.0001; 95% CI 25-54%) after cessation of treatment. The differences between the two regimens were most pronounced in men and in patients with complicating factors such as diabetes mellitus and urinary tract abnormalities. The clinical response during treatment did not differ between the two groups, but symptomatic recurrences at follow-up were more common in the cefadroxil group (28% versus 3%; p less than 0.0001; 95% CI 14-36%). Adverse events were more often reported by patients receiving cefadroxil (39% versus 22%; p = 0.011; 95% CI 4-30%) and consisted mainly of gastrointestinal disturbances and vulvo-vaginitis. In terms of bacteriological and clinical efficacy and safety, a two-week course of norfloxacin was superior to a two-week course of cefadroxil for oral treatment of community-acquired acute pyelonephritis.

The effect of acute administration of the mycotoxin zearalenone to female pigs.

Crystalline zearalenone was administered to young female pigs at dose levels of 0, 3.5, 7.5 and 11.5 mg zearalenone/kg body weight. All animals receiving the mycotoxin exhibited vulva vaginitis and had enlarged reproductive tracts, 1 week after dosing. Free zearalenone was found in the blood, feces and urine of dosed animals. The highest zearalenone level detected was 2.61 ng/ml from a pig that received the 7.5 mg/kg dose. After 24 hours, feces collected contained on average upto 308 ng zearalenone per g of dried feces. Zearalenone levels of up to 59 ng/ml, and alpha-zearalenol levels of up to 155 ng/ml urine were found. beta-zearalenol was also detected in the urine.

[Principle complications and contraindications of the use of oral contraceptives]. / Considerazioni sulle principali complicanze e controindicazioni dell'uso dei contraccettivi orali.

PIP: The use of oral contraceptives should at all times be under physician's control. Most contraindications and complications from oral contraceptives are now a thing of the past, when higher doses were prescribed. However oral contraceptives are still responsible for many side effects and complications. Some of these are gastrointestinal problems; menstruation disorders, such as spotting or amenorrhea; decreased libido; increase in body weight; mastodynia; blood coagulation effects; lipid and carbohydrate metabolic effects; ophthalmological and dermatological problems; and, possibly, an increase in susceptibility to some infectious diseases. Patients with hypertension; with heart or hepatic diseases; with a history of family thrombolic accidents; with diabetes; or hyperthyroidism should utilize another form of contraception. Oral contraceptives are totally contraindicated for obese or emotionally depressed people, for pregnant or nursing mothers, for women with uterine or breast cancer, and for adolescents.^ieng