Potential clinical applications of current and future oral forms of desmopressin (Review).

Desmopressin is a synthetic analogue of vasopressin and a selective vasopressin receptor 2 agonist. It was first synthesised in 1967 and utilised for its antidiuretic properties. It is also used in bleeding disorders to enhance clotting.

A novel pathway for the induction of DNA damage in human spermatozoa involving extracellular cell-free DNA.

DNA damage is a common feature of human spermatozoa associated with an impaired capacity to fertilize the oocyte and an increased mutational load in the offspring. However, the etiology of this damage remains poorly defined. In this study we demonstrate that a major pathway for the induction of DNA damage in mammalian spermatozoa is triggered by exposure to exogenous cell free DNA (cfDNA).

Achieving clinically meaningful quality of life benefits in nocturia takes time: Results from a long-term, multicenter phase 3 study of desmopressin in Japanese patients.

Objectives: To investigate the long-term efficacy, quality of life (QoL), and safety of desmopressin orally disintegrating tablets (ODTs) in Japanese patients with nocturia.

Methods: A long-term, multicenter phase 3 study was conducted that enrolled Japanese male and female patients with nocturia (NCT03051009). Male patients received desmopressin 25- or 50-μg ODTs, and female patients received desmopressin 25-μg ODTs for up to 1 year.

The use of 5-aminosalicylates in Crohn's disease: a retrospective study using the UK Clinical Practice Research Datalink.

Background: There are few recent studies on the use of 5-aminosalicylates (5-ASA) as therapy for Crohn's disease (CD) in routine clinical practice. The aim of this database investigation was to provide real-world evidence on 5-ASA use in CD.

Methods: Patients with CD, aged ≥18 years when first prescribed 5-ASA (index date) and having received 5-ASA at any time between 01 January 2006 and 07 May 2018, were included for analysis.

Kisspeptin treatment induces gonadotropic responses and rescues ovulation in a subset of preclinical models and women with polycystic ovary syndrome.

Study Question: Can kisspeptin treatment induce gonadotrophin responses and ovulation in preclinical models and anovulatory women with polycystic ovary syndrome (PCOS)?

Summary Answer: Kisspeptin administration in some anovulatory preclinical models and women with PCOS can stimulate reproductive hormone secretion and ovulation, albeit with incomplete efficacy.

What Is Known Already: PCOS is a prevalent, heterogeneous endocrine disorder, characterized by ovulatory dysfunction, hyperandrogenism and deregulated gonadotrophin secretion, in need of improved therapeutic options. Kisspeptins (encoded by Kiss1) are master regulators of the reproductive axis, acting mainly at GnRH neurons, with kisspeptins being an essential drive for gonadotrophin-driven ovarian follicular maturation and ovulation.

Efficacy and safety of 25 and 50 μg desmopressin orally disintegrating tablets in Japanese patients with nocturia due to nocturnal polyuria: Results from two phase 3 studies of a multicenter randomized double-blind placebo-controlled parallel-group development program.

This study assessed the efficacy and safety of desmopressin orally disintegrating tablets (ODTs) in Japanese males (50 and 25 μg) and females (25 μg) with nocturia due to nocturnal polyuria (NP). Two Phase 3 randomized double-blind placebo-controlled studies of 342 males and 190 females with nocturia due to NP were conducted. The primary endpoint was change from baseline in mean number of nocturnal voids.

Methods to Study Colon Release: State of the Art and An Outlook on New Strategies for Better Biorelevant Release Media.

The primary focus of this review is a discussion regarding in vitro media for colon release, but we also give a brief overview of colon delivery and the colon microbiota as a baseline for this discussion. The large intestine is colonized by a vast number of bacteria, approximately 10 per gram of intestinal content. The microbial community in the colon is complex and there is still much that is unknown about its composition and the activity of the microbiome.

Patient experience in a randomized trial of a weekly progesterone vaginal ring versus a daily progesterone gel for luteal support after in vitro fertilization.

Objective: To assess patient experience and convenience of using progesterone vaginal ring (VR) versus vaginal gel for women requiring luteal phase support during in vitro fertilization (IVF).

Design: Post hoc analysis of a prospective, randomized, single-blind, multicenter, phase 3 clinical trial.

Setting: Twenty-two U.

Budesonide with multi-matrix technology as second-line treatment for ulcerative colitis: evaluation of long-term cost-effectiveness in the Netherlands.

Aims: Budesonide with multi-matrix technology (MMX) is an oral corticosteroid, shown to have high topical activity against ulcerative colitis (UC) while maintaining low systemic bioavailability with few adverse events. The aim of this study was to evaluate the cost-effectiveness of budesonide MMX versus commonly used corticosteroids, in the second-line treatment of active mild-to-moderate UC in the Netherlands.

Materials And Methods: An eight-state Markov model with an 8 week cycle length captured remission, four distinct therapy stages, hospitalization, possible colectomy and mortality.

Efficacy and safety of testosterone replacement gel for treating hypogonadism in men: Phase III open-label studies.

Efficacy and safety of testosterone gel 2% (TG) were evaluated in two phase 3, open-labelled, single-arm, multicentre studies (000023 and extension study 000077). Hypogonadal men having serum testosterone levels <300 ng/dl at two consecutive measurements were included. Study duration was 9 months (000023: 3 months; 000077: 6 months).

Delaying time to first nocturnal void may have beneficial effects on reducing blood glucose levels.

Experimental studies disrupting sleep and epidemiologic studies of short sleep durations indicate the importance of deeper and longer sleep for cardiometabolic health. We examined the potential beneficial effects of lengthening the first uninterrupted sleep period (FUSP) on blood glucose. Long-term data (≥3 months of treatment) were derived from three clinical trials, testing low-dose (10-100 µg) melt formulations of desmopressin in 841 male and female nocturia patients (90 % of which had nocturnal polyuria).

Desmopressin as an adjuvant to opioids or NSAIDs in treatment of renal colic: a nationwide register-based study.

Aims: Desmopressin has been reported to be effective as an adjuvant to opioids or NSAIDs in management of pain in renal colic; however real-life data are lacking on the utilisation of desmopressin in this patient segment.

Methods: The Danish National Prescription Registry data-linked with Danish National Patient Registry during a 3-year period from 2009 to 2011 was used to study prescriptions for desmopressin in renal colic.

Results: We identified 888 desmopressin prescriptions for renal colic, dispensed to 95 patients.

Quality of life improvement in patients treated with degarelix versus leuprorelin for advanced prostate cancer.

Purpose: We used responses to questionnaires included in the CS21 degarelix trial and published mapping algorithms to address the paucity of evidence for health related quality of life in patients with advanced hormone dependent prostate cancer treated with degarelix.

Materials And Methods: We measured health related quality of life in 610 patients enrolled in the CS21 trial using SF-12® and EORTC QLQ-C30. Based on responses to these questionnaires we estimated patient utility using 4 published mapping algorithms.

The Nocturia Impact Diary: a self-reported impact measure to complement the voiding diary.

Background: Nocturia is a chronic, fluctuating disease that disrupts sleep and has a wide-ranging impact on quality of life. Valid tools to measure the patient-reported impact of nocturia are essential for evaluating the value of treatment, but the available tools are suboptimal.

Objectives: This study reports the development and validation of the Nocturia Impact Diary-an augmented form of the Nocturia Quality of Life questionnaire designed to be completed in conjunction with the widely used 3-day voiding diary.

National Surveillance of Central Diabetes Insipidus (CDI) in Denmark: results from 5 years registration of 9309 prescriptions of desmopressin to 1285 CDI patients.

Context: Epidemiological data for central diabetes insipidus (CDI) are sparse.

Objective: The purpose of this study was to provide accurate epidemiological data on CDI on a national level.

Design And Setting: This was a drug utilization and patient registry study during a 5-year period from 2007 to 2011.

Desmopressin melt improves response and compliance compared with tablet in treatment of primary monosymptomatic nocturnal enuresis.

Unlabelled: Primary nocturnal enuresis is a prevalent childhood condition that can persist into adulthood. Desmopressin is an antidiuretic available as orally disintegrating lyophilisate (melt) or solid tablet. Recent findings suggesting different food interactions and clinical characteristics, including compliance, between desmopressin melt and tablet motivated a post hoc analysis of a previously reported randomised, crossover study.

Temporal delays and individual variation in antidiuretic response to desmopressin.

This study aimed to estimate the relationship between pharmacokinetics and the antidiuretic effect of desmopressin. In the investigator-blind, randomized, parallel group study, 5 dose groups and 1 placebo group, each consisting of 12 healthy, overhydrated, nonsmoking male subjects 18-55 yr of age were infused intravenously over 2 h with placebo or 30, 60, 125, 250, and 500 ng desmopressin in 50 ml of normal saline. Plasma desmopressin and urine osmolality rose by variable amounts during the infusions of 60, 125, 250, and 500 ng desmopressin.

Long-term durability of the response to desmopressin in female and male nocturia patients.

Aims: To explore the durability of efficacy and gender differences during chronic administration of desmopressin in nocturia.

Methods: This pooled analysis of three short-term efficacy studies, with extensions, of desmopressin administered as orally disintegrating tablet (ODT) or solid tablet in nocturia treatment, comprised 351 patients completing 40-56 weeks' treatment. Efficacy endpoints of change in number of nocturnal voids and duration of initial undisturbed sleep period from baseline were analyzed to determine response durability and gender differences.

The evolutionary origin of the vasopressin/V2-type receptor/aquaporin axis and the urine-concentrating mechanism.

In this mini-review, current evidence for how the vasopressin/V2-type receptor/aquaporin axis developed co-evolutionary as a crucial part of the urine-concentrating mechanism will be presented. The present-day human kidney, allowing the concentration of urine up to a maximal osmolality around 1200 mosmol kg(-1)-or urine to plasma osmolality ratio around 4-with essentially no sodium secreted is the result of up to 3 billion years evolution. Moving from aquatic to terrestrial habitats required profound changes in kidney morphology, most notable the loops of Henle modifying the kidneys from basically a water excretory system to a water conserving system.