pharmacodynamic evaluation of the novel nystatin derivative BSG005 in the invasive candidiasis and invasive pulmonary aspergillosis mouse models.

Nystatin, a polyene, is one of the oldest antifungal drugs with wide potency. BSG005 is a novel, chemically modified, nystatin-like molecule in development for systemic therapy. We evaluated the pharmacokinetic/pharmacodynamic (PK/PD) relationships and target exposures using invasive pulmonary aspergillosis (IPA) and invasive candidiasis (IC) infection models for BSG005 against common fungal pathogens including , , , and .

Follicle-stimulating hormone receptor expression in advanced atherosclerotic plaques.

Experimental evidence indicates that follicle-stimulating hormone (FSH), an essential hormone for reproduction, can act directly on endothelial cells inducing atherosclerosis activation and development. However, it remains unknown whether the FSH-receptor (FSHR) is expressed in human atherosclerosis plaques. To demonstrate the FSHR presence, we used immunohistochemical and immunoelectron microscopy involving a specific monoclonal antibody FSHR1A02 that recognizes an epitope present in the FSHR-ectodomain.

Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Prostate Cancer: The Primary Results of the PRONOUNCE Randomized Trial.

Background: The relative cardiovascular safety of gonadotropin-releasing hormone (GnRH) antagonists compared with GnRH agonists in men with prostate cancer and known atherosclerotic cardiovascular disease remains controversial.

Methods: In this international, multicenter, prospective, randomized, open-label trial, men with prostate cancer and concomitant atherosclerotic cardiovascular disease were randomly assigned 1:1 to receive the GnRH antagonist degarelix or the GnRH agonist leuprolide for 12 months. The primary outcome was the time to first adjudicated major adverse cardiovascular event (composite of death, myocardial infarction, or stroke) through 12 months.

Assessment of the Most Impactful Combination of Factors Associated with Nocturia and to Define Nocturnal Polyuria by Multivariate Modelling.

Background: Nocturia is common and associated with multiple disease states. Many potential mechanisms have been proposed for nocturia, which also remains challenging to manage.

Purpose: To use multivariate analysis to determine which combinations of factors can accurately discriminate clinically significant nocturia in patients to facilitate clinical management and treatment decisions.

Cardiovascular Safety of Degarelix Versus Leuprolide for Advanced Prostate Cancer: The PRONOUNCE Trial Study Design.

Objectives: This study will compare the incidence of major adverse cardiovascular events (MACEs) with androgen deprivation therapy (ADT) among men with advanced prostate cancer who are being treated with a gonadotropin-releasing hormone (GnRH) antagonist versus a GnRH agonist.

Background: Treatment of advanced prostate cancer with ADT might increase the risk of subsequent cardiovascular events among men with known atherosclerotic cardiovascular disease (ASCVD), but a recent meta-analysis suggested that this risk might be lower with ADT using a GnRH antagonist versus a GnRH agonist.

Methods: PRONOUNCE is a multicenter, prospective, randomized, open, blinded endpoint trial that will enroll approximately 900 patients with advanced prostate cancer and pre-existing ASCVD who will be treated with ADT.

Therapeutic endometrial scratching and implantation after in vitro fertilization: a multicenter randomized controlled trial.

Objective: To study whether endometrial scratching in the luteal phase before ovarian stimulation increases clinical pregnancy rates in women with one or more previous implantation failures.

Design: A nonblinded multicenter randomized clinical trial.

Setting: Fertility clinics.

Identifying men with global polyuria on a nocturnal-only voiding diary.

Aims: Nocturnal polyuria (NP) and global polyuria (GP) are not mutually exclusive. However, by rate, the common criteria for GP (40 mL/kg/24 hours [117 mL/kg/hour in a 70-kg individual] or 3000 mL/24 hours [125 mL/h]) are more stringent than those for NP (90 mL/hour during the sleep period or NP index [NPi; nocturnal volume/24-hour volume] > 0.33 [no minimum rate]).

Development of a multivariate prediction model for nocturia, based on urinary tract etiologies.

Purpose: The main objective of our study was to determine which combination of modifiable and non-modifiable parameters that could discriminate patients with nocturia from those without nocturia. This was a post-hoc analysis of 3 prospective, observational studies conducted in Ghent University. Participants completed frequency volume chart (FVC) to compare characteristics between patients with and without nocturia.

[Preimplantation genetic diagnosis].

In Denmark, preimplantation genetic diagnosis (PGD) is offered within the public healthcare to families with a known risk of an inherited disease in a child - as an alternative to prenatal diagnosis. It is a well-established technique with rather well-described perinatal- and neonatal outcomes, being comparable to what is seen following in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). The most common strategy is now to perform trophectoderm biopsy and then vitrify, while the diagnostic test is performed.

Systematic review of proposed definitions of nocturnal polyuria and population-based evidence of their diagnostic accuracy.

Background Evidence of diagnostic accuracy for proposed definitions of nocturnal polyuria is currently unclear. Purpose Systematic review to determine population-based evidence of the diagnostic accuracy of proposed definitions of nocturnal polyuria based on data from frequency-volume charts. Methods Seventeen pre-specified search terms identified 351 unique investigations published from 1990 to 2016 in BIOSIS, Embase, Embase Alerts, International Pharmaceutical Abstract, Medline, and Cochrane.

Follicle-Stimulating Hormone Receptor Expression in Endometriotic Lesions and the Associated Vasculature: An Immunohistochemical Study.

Follicle-stimulating hormone receptor (FSHR) is present on endothelial cells of blood vessels and endometrial glands of the proliferative and secretory endometrium. So far, the expression of FSHR in endometriosis has not been studied. We evaluated FSHR expression in 194 tissue specimens representing 3 relevant types of endometriosis: rectovaginal endometriotic nodules, ovarian endometriotic cysts, and peritoneal endometriotic implants.

Long-term tolerability and efficacy of degarelix: 5-year results from a phase III extension trial with a 1-arm crossover from leuprolide to degarelix.

Objective: To demonstrate the safety and efficacy of up to 5 years of degarelix treatment and the effects of crossing over from leuprolide to degarelix in the extension phase of a phase III pivotal 1-year trial.

Methods: Patients receiving degarelix who completed the 1-year trial continued on 80 mg (n = 125) or 160 mg (n = 126) maintenance doses. Patients who received leuprolide were rerandomized to degarelix 240/80 mg (n = 69) or 240/160 mg (n = 65).

Cardiovascular morbidity associated with gonadotropin releasing hormone agonists and an antagonist.

Background: Androgen deprivation therapy (ADT) is associated with increased cardiovascular morbidity.

Objective: To determine whether cardiovascular morbidity differs following initiation of gonadotropin-releasing hormone (GnRH) agonists compared with an antagonist.

Design, Setting, And Participants: Pooled data from six phase 3 prospective randomized trials that recruited 2328 men between 2005 and 2012 to compare the efficacy of GnRH agonists against an antagonist.

The effect of baseline testosterone on the efficacy of degarelix and leuprolide: further insights from a 12-month, comparative, phase III study in prostate cancer patients.

Objective: To investigate the effects of baseline testosterone on testosterone control and prostate-specific antigen (PSA) suppression using data from a phase III trial (CS21) comparing degarelix and leuprolide in prostate cancer.

Methods: In CS21, patients with histologically confirmed prostate cancer (all stages) were randomized to degarelix 240 mg for 1 month followed by monthly maintenance doses of 80 or 160 mg, or leuprolide 7.5 mg/month.

Rapid elimination kinetics of free PSA or human kallikrein-related peptidase 2 after initiation of gonadotropin-releasing hormone-antagonist treatment of prostate cancer: potential for rapid monitoring of treatment responses.

Background: The utility of conventional prostate-specific antigen (PSA) measurements in blood for monitoring rapid responses to treatment for prostate cancer is limited because of its slow elimination rate. Prior studies have shown that free PSA (fPSA), intact PSA (iPSA) and human kallikrein-related peptidase 2 (hK2) are eliminated more rapidly after radical prostatectomy. In contrast, all three markers have similarly slow elimination rates after castration induced by gonadotropin-releasing hormone (GnRH) agonists, possibly due to the slow onset of castration.

A phase III extension trial with a 1-arm crossover from leuprolide to degarelix: comparison of gonadotropin-releasing hormone agonist and antagonist effect on prostate cancer.

Purpose: We investigated the efficacy and safety of degarelix treatment and the effects of switching from leuprolide to degarelix in an ongoing extension study with a median 27.5-month followup of a pivotal 1-year prostate cancer trial.

Materials And Methods: Patients who completed a 1-year pivotal phase III trial continued on the same monthly degarelix maintenance dose (160 or 80 mg in 125 each), or were re-randomized from leuprolide 7.

Cardiovascular safety of degarelix: results from a 12-month, comparative, randomized, open label, parallel group phase III trial in patients with prostate cancer.

Purpose: We assessed the cardiovascular safety profile of degarelix, a new gonadotropin-releasing hormone antagonist.

Materials And Methods: This is the first report to our knowledge on cardiovascular safety data from a completed 1-year randomized controlled trial of leuprolide acetate vs degarelix. Outcomes considered in these analyses included the QT interval by central reading and analysis, and cardiovascular adverse events.

Changes in alkaline phosphatase levels in patients with prostate cancer receiving degarelix or leuprolide: results from a 12-month, comparative, phase III study.

Study Type - Therapy (RCT) Level of Evidence 1b OBJECTIVE To compare the activity of degarelix, a new gonadotrophin-releasing hormone (GnRH) blocker, with leuprolide depot 7.5 mg in the control of total serum alkaline phosphatase (S-ALP) levels in patients with prostate cancer. PATIENTS AND METHODS In the randomized, phase III trial (CS21), patients with histologically confirmed prostate cancer (all stages), were randomized to one of three regimens: degarelix subcutaneous 240 mg for 1 month followed by monthly maintenance doses of 80 mg or 160 mg, or intramuscular leuprolide 7.

The efficacy and safety of degarelix: a 12-month, comparative, randomized, open-label, parallel-group phase III study in patients with prostate cancer.

Objective: To evaluate the efficacy and safety of degarelix, a new gonadotrophin-releasing hormone (GnRH) antagonist (blocker), vs leuprolide for achieving and maintaining testosterone suppression in a 1-year phase III trial involving patients with prostate cancer.

Patients And Methods: In all, 610 patients with adenocarcinoma of the prostate (any stage; median age 72 years; median testosterone 3.93 ng/mL, median prostate-specific antigen, PSA, level 19.

A 1-year, open label, randomized phase II dose finding study of degarelix for the treatment of prostate cancer in North America.

Purpose: Degarelix is a gonadotropin-releasing hormone receptor antagonist (blocker) with rapid onset of action suppressing gonadotropins, testosterone and prostate specific antigen in prostate cancer. In the present open label, randomized study in North America we evaluated the efficacy and safety of a starting dose of 200 mg degarelix followed by monthly injections of 60 or 80 mg during 1 year of prostate cancer treatment.

Materials And Methods: A total of 127 patients (median age 76 years, range 47 to 93) with histologically confirmed prostate cancer were enrolled in the study.