Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

The promise of N-acetylcysteine in the treatment of obsessive-compulsive disorder

No abstract available (Letter to the Journal

Vaginal-Laparoscopic Repair (VLR) of Primary and Persistent Vesico-Vaginal Fistula: Description of a New Technique and Surgical Outcomes

The main aim of our study was to describe the surgical technique and evaluate the feasibility, efficacy and safety of a vaginal-laparoscopic repair (VLR) of iatrogenic vesico-vaginal fistulae (VVF). Between April-2009 and November-2017, we retrospectively reviewed all clinical, radiological and surgical details of surgery for benign or malignant disease and ended up with VVF. All patients were diagnosed by CT urogram, cystogram and clinical test. The surgical technique was standardised and is described here. Eighteen patients developed VVF after hysterectomy, three after caesarean section and three after hysterectomy and pelvic lymphadenectomy. Twenty-two patients had an average 3 (range 1-5) attempts at fistula repair in other hospitals. In one patient, five attempts were made. The mean size of the fistula was 2.4 cm (range 0.7-3.1 cm). A median 8 weeks (6-16) conservative management with Foley catheter failed in all patients. No conversion to laparotomy and no complication occurred at VLR. Median hospitalisation was 1.4 days (range 1-3). The latter confirmed all patients were dry and tested negative at a repeated filling test. At 36 months follow-up, all patients remained dry. In conclusion, VLR successfully repaired VVF in all patients with primary and persistent VVF. The technique was safe and effective

Androgens and Female Sexuality: Molecular Insights, Neuroendocrine Crosstalk and Future Therapeutic Directions

Objective: The scientific community has recently directed its attention towards investigating the role of androgens in female sexuality. This narrative review aims to elucidate the central and peripheral androgen-mediated mechanisms involved in female sexual health and function. Additionally, the current state of androgen therapeutic options is discussed. Mechanism: We searched several scientific literature databases, including EMBASE, MEDLINE, PubMed Central, and Scopus, utilizing keywords, index terms, and MeSH terms, such as “androgen*”, “female sexuality”, “female sexual function”, “women’s sexual dysfunctions”, “androgen therapy in women”, and various combinations thereof. Findings in Brief: Progesterone or estrogens are commonly prescribed as first-line treatments for female sexual dysfunctions. However, these medications may frequently lead to therapeutic failure and cause harm by increasing sex-hormone-binding-globulin plasma levels and decreasing testosterone plasma concentrations. Currently, there are limited androgen therapies available for women, and the evidence for their effectiveness and safety is still limited. Conclusions: The knowledge of neuroendocrine interactions that underlie sexual arousal and pleasure is rapidly expanding, and ongoing research is striving to develop more appropriate clinical practices for managing sexual dysfunctions in women