The Oxytocin Antagonist Cligosiban Fails to Prolong Intravaginal Ejaculatory Latency in Men with Lifelong Premature Ejaculation: Results of a Randomized, Double-Blind, Placebo-Controlled Phase IIb trial (PEDRIX).

INTRODUCTION: Cligosiban is an orally administered, centrally penetrant oxytocin receptor antagonist being developed to treat premature ejaculation (PE). AIM: To determine the efficacy of 3 dose levels of cligosiban caplets to prolong intravaginal ejaculation latency time (IELT) and improve patient-reported outcomes in men with lifelong PE. METHODS: Patients recorded details of at least 4 sexual intercourse events during a 4-week run-in period, after which they underwent baseline assessments. Patients were eligible for the study if their stopwatch-assessed IELT was ≤1 minute in ≥75% of intercourse attempts and if they met other diagnostic criteria for lifelong PE. Eligible patients (target 220 evaluable) were randomized to double-blind cligosiban 400, 800, or 1200 mg or matching placebo caplets (to be taken 1 to 6 hours prior to sexual activity). Assessments were conducted at 2, 4, and 8 weeks. MAIN OUTCOME MEASURE: Efficacy measures were comprised of IELT, self-rating of ejaculation control and ejaculation-related distress (recorded in an electronic diary after each intercourse attempt), premature ejaculation profile, Patient's Global Impression of Severity, and the Clinical Global Impression of Change. RESULTS: There were no clinically or statistically significant differences between cligosiban (at any dose level) and placebo for the primary endpoint (change in geometric IELT) or any of the secondary endpoints. Cligosiban was well tolerated with a side-effect profile similar to placebo. CLINICAL IMPLICATIONS: This Phase IIb study failed to demonstrate the potential for cligosiban, an oxytocin antagonist, to successfully treat symptoms of severe lifelong PE at doses up to 1200 mg. STRENGTHS AND LIMITATIONS: This was a Phase IIb, randomized, double-blind, placebo-controlled study that was adequately powered but failed to detect a clinically meaningful or statistical difference in change in IELT between cligosiban at 3 dose levels and placebo. This is in contrast to a similarly designed proof-of-concept study where cligosiban was flexibly dosed at doses up to 800 mg and did demonstrate clinically meaningful and statistically significant changes in efficacy parameters. The reasons for this disparity are not known. CONCLUSIONS: Cligosiban was well tolerated but failed to demonstrate efficacy for the treatment of men with lifelong PE at doses up to 1200 mg. Althof S, Osterloh IH, Muirhead GJ, et al. The Oxytocin Antagonist Cligosiban Fails to Prolong Intravaginal Ejaculatory Latency in Men with Lifelong Premature Ejaculation: Results of a Randomized, Double-Blind, Placebo-Controlled Phase IIb trial (PEDRIX). J Sex Med 2019; 16:1188-1198.

Content Validity of the Premature Ejaculation Profile, Original and Per-Event Formats, in Men with Lifelong Premature Ejaculation.

BACKGROUND: The Premature Ejaculation Profile (PEP) is a patient-reported outcome (PRO) measure that is widely used in clinical research in men with premature ejaculation (PE) but has not been fully validated for men meeting the current International Society for Sexual Medicine (ISSM) definition of lifelong PE. AIM: To explore the content validity of the PEP (original 1-month recall version and new event-driven version) in men meeting current definitions of lifelong PE and to understand the relevance of the concept of ejaculation control. METHODS: In-depth individual interviews were conducted with 24 men in a stable heterosexual relationship, including 15 with lifelong PE, 4 with acquired PE (with intravaginal ejaculation latency time values confirmed during a 4-week period of no treatment), and 5 with no sexual dysfunction. Initial concept elicitation explored individual experiences of having PE (in those with PE), experiences of control, and impact on sexual life. This was followed by a cognitive debriefing of the PEP versions. MAIN OUTCOME MEASURE: Thematic analysis was used to identify key concepts of PE, understand the experience of control in men with and without PE, and confirm understanding and relevance of questions from original and event-driven versions of the PEP. RESULTS: The interviews confirmed substantial negative consequences for men with lifelong PE. Men with and without PE could describe ejaculation control (or lack of it). The PEP was shown to cover the key concepts in PE, and the questions were easily understood in both the original or event-driven versions. The items were comprehensive, and the concept of ejaculation control was confirmed. A 1- or 2-category change in each item of the PEP was considered clinically meaningful. CLINICAL IMPLICATIONS: The PEP (original and per-event) has strong content validity for use in clinical research studies of men meeting the ISSM definition of lifelong PE. STRENGTHS & LIMITATIONS: This study addressed gaps in previously published research on the development and validation of the PEP and also confirmed that a new event-driven version is also suitable for use in research. However, the study was limited mainly to men meeting a strict definition of lifelong PE; in addition, homosexual men and those not in stable long-term relationships were not studied. CONCLUSION: Both the original and per-event PEP versions were shown to have strong content validity and be acceptable for use in men with lifelong PE. Burbridge C, Symonds T, Osterloh IH, et al. Content Validity of the Premature Ejaculation Profile, Original and Per-Event Formats, in Men with Lifelong Premature Ejaculation. J Sex Med 2019;16:569-576.

Interprofessional Simulations Promote Knowledge Retention and Enhance Perceptions of Teamwork Skills in a Surgical-Trauma-Burn Intensive Care Unit Setting.

BACKGROUND: The current state of health care encompasses highly acute, complex patients, managed with ever-changing technology. The ability to function proficiently in critical care relies on knowledge, technical skills, and interprofessional teamwork. Integration of these factors can improve patient outcomes. Simulation provides "hands-on" practice and allows for the integration of teamwork into knowledge/skill training. However, simulation can require a significant investment of time, effort, and financial resources. The Institute of Medicine recommendations from 2015 include "strengthening the evidence base for interprofessional education (IPE)" and "linking IPE with changes in collaborative behavior." In one surgical-trauma-burn intensive care unit (STBICU), no IPE existed. The highly acute and diverse nature of the patients served by the unit highlights the importance of appropriate training. This is heightened during critical event situations where patients deteriorate rapidly and the team intervenes swiftly. PURPOSE: The aims of this study were to (1) evaluate knowledge retention and analyze changes in perceptions of teamwork among nurses and resident physicians in a STBICU setting after completion of an interprofessional critical event simulation and (2) provide insight for future interprofessional simulations (IPSs), including the ideal frequency of such training, associated cost, and potential effect on nursing turnover. DESIGN: A comparison-cohort pilot study was developed to evaluate knowledge retention and analyze changes in perceptions of teamwork. METHODS: A 1-hour critical event IPS was held for nurses and resident physicians in a STBICU setting. A traumatic brain injury patient with elevated intracranial pressure, rapid deterioration, and cardiac arrest was utilized for the simulation scenario. The simulation required the team to use interventions to reduce elevated intracranial pressure and then perform cardiac resuscitation according to Advanced Cardiac Life Support guidelines. A semistructured debriefing guided by the TENTS tool highlighted important aspects of teamwork. Participants took knowledge and Teamwork Skills Scale (TSS) pretests, posttests, and 1-month posttests. Mean scores were calculated for each time point (pre, post, and 1-month post), and paired t tests were used to evaluate changes. RESULTS: Mean knowledge test and TSS scores both significantly increased after the simulation and remained significantly elevated at 1-month follow-up. Participants recommended retraining intervals of 3 to 6 months. Cost of each simulation was estimated to be $324.44. Analysis of nursing turnover rates did not demonstrate a statistically significant reduction in turnover; however, confounding factors were not controlled for. CONCLUSION: Significant improvements on both knowledge test and TSS scores demonstrate the effectiveness of the intervention, and retention of the information gained and teamwork skills learned. Participants valued the intervention and recommended to increase the frequency of training. Future studies should develop a framework for "best practice" IPS, analyze the relationship with nursing turnover, and ultimately seek correlations between IPS and improved patient outcomes.

"I Don't Want Them to Feel Different": A Mixed Methods Study of Parents' Beliefs and Dietary Management Strategies for Their Young Children with Type 1 Diabetes Mellitus.

BACKGROUND: Many young children with type 1 diabetes mellitus (T1DM) do not consume a healthful diet; exactly why this occurs despite T1DM education remains poorly understood. OBJECTIVE: This study describes parents' perceptions of healthful eating for T1DM in young children and identifies factors related to parents' dietary management. DESIGN: A cross-sectional, mixed-methods study was performed. Parents completed a questionnaire, 3-day weighed diet record, and a semi-structured interview regarding their perceptions of healthful eating for T1DM and their dietary management practices. PARTICIPANTS/SETTING: Twenty-three families, recruited from a pediatric diabetes clinic in the midwestern United States between February 2012 and April 2013, participated. Eligible families had a child with T1DM who was 1 to 6 years old, at least 6 months from diagnosis, and was following an intensive insulin regimen. STATISTICAL ANALYSES PERFORMED: Mean scores and percentages were calculated from the diet diaries and parent questionnaires, and parents' interviews were coded to identify common themes. RESULTS: Results showed that while parents may believe they know what constitutes a healthful diet for T1DM, they do not always feed their child a healthful diet. Parent-identified barriers to healthful eating included limited time to prepare homemade meals, perceived higher costs of healthier foods, the influence of peers on children's food preferences, and picky eating. Parents also discussed a desire not to limit their child's diet or make their child "feel different," which many parents said often led them to give into their child's requests for less healthful food options. CONCLUSIONS: Parents of young children with T1DM identified several barriers to healthful eating that are common for all parents, such as time constraints, expense, and child food preferences. However, unique themes emerged, including parents' desire not to limit their child's diet or make their child "feel different." Nutrition components of T1DM education should include psychological and behavioral strategies to help parents manage these unique concerns.