A Double-Blind, Placebo-Controlled Parallel Group Study to Evaluate the Effect of a Single Oral Dose of 5-HT1A Antagonist GSK958108 on Ejaculation Latency Time in Male Patients Suffering From Premature Ejaculation.

BACKGROUND: Premature ejaculation (PE) is a common male neurobiological sexual disorder, related to a disturbance in central serotonin (5-hydroxytryptamine or 5-HT) neurotransmission. AIM: To assess the efficacy of a single oral dose of 5HT1A receptor antagonist GSK958108 on ejaculation latency time (ELT) in male subjects suffering from PE. METHODS: A total of 35 male subjects were enrolled in a Phase 1 double-blind, placebo-controlled, parallel group masturbation-model study. All subjects completed the study. No subject was withdrawn from the study. There were no major protocol deviations reported during the study. OUTCOMES: The primary outcome of the study was to evaluate the effect of a single oral dose of 5HT1A receptor antagonist GSK958108 on ELT as measured in the masturbation model; additionally, we investigated drug's safety and tolerability. RESULTS: In the 3 mg GSK958108 treatment group, the ELT was estimated to be 16% longer (1.542 vs 1.328, 95% CI: -16% to +61%) than if the subjects had taken placebo. In the 7 mg GSK958108 treatment group, the ELT was estimated to be 77% longer (2.346 vs 1.328, 95% CI: +28% to +144%) than in the placebo group. The systemic exposure to GSK958108 increased with dosage between 3 mg and 7 mg. A significant trend toward an increase of ELT was observed with increasing plasma concentrations of GSK958108. A total of 4 patients all treated with 7 mg dose experienced minor drug related adverse events (5 adverse events in 4 patients): somnolence (n = 3), headache (n = 1), tinnitus (n = 1). CLINICAL IMPLICATIONS: In the current double-blind, placebo-controlled parallel group study the 5HT1A receptor antagonist GSK958108 was tested in 3 mg and 7 mg doses for PE treatment in humans. It was shown that GSK958108 significantly delayed ejaculation showing a new and safe alternative in PE treatment. STRENGTHS & LIMITATIONS: The present study showed innovative results suggesting an important role of 5HT1A receptor antagonist in the PE treatment. However, the use of masturbation model and the small population are the main limitations of this investigation. CONCLUSION: 5HT1A receptor antagonist GSK958108 3 mg per day and 7 mg per day was found to be well-tolerated, safe and effective for the treatment of PE subjects and demonstrated a strong association between 5HT1A receptors and ejaculation control in humans (NCT00861484). Migliorini F, Tafuri A, Bettica P, et al. A Double-Blind, Placebo-Controlled Parallel Group Study to Evaluate the Effect of a Single Oral Dose of 5-HT1A Antagonist GSK958108 on Ejaculation Latency Time in Male Patients Suffering From Premature Ejaculation. J Sex Med 2021;18:63-71.

Consulting "Dr. Google" for Prostate Cancer Treatment Options: A Contemporary Worldwide Trend Analysis.

BACKGROUND: In the era of digital data, the Internet has become the primary source from which individuals draw healthcare information. OBJECTIVE: The aim of the present study is to determine worldwide public interest in prostate cancer (PCa) treatments, their penetrance and variation, and how they compare over time. DESIGN, SETTING, AND PARTICIPANTS: An analysis of worldwide search-engine trends included electronic Google queries from people who searched PCa treatment options from January 2004 to August 2018, worldwide. Join-point regression was performed. Comparisons of annual relative search volume (ARSV), average annual percentage change (AAPC), and temporal patterns were analysed to assess loss or gain of interest. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Evaluations were made regarding (1) interest in PCa treatments, (2) comparison of people's interest, and (3) impact of the US Preventive Service Task Force (USPSTF) screening recommendation and National Comprehensive Cancer Network (NCCN) guideline endorsements on Internet searching for PCa treatments. RESULTS AND LIMITATIONS: The mean ARSV for "prostatectomy" was 73% in 2004 and decreased thereafter, reaching a nadir of 36% in 2014 (APC: -7.2%; 95% confidence interval [CI] -7.8, -6.7; p < 0.01). Similarly, decreased interest was recorded for radiation therapy (AAPC: -3.2%; p = 0.1), high-intensity focused ultrasound (AAPC: -2.3%; p = 0.1), hormonal therapy (AAPC: -11.6%; p < 0.01), ablation therapy (AAPC: -4.1%; p < 0.01), cryotherapy (AAPC: -9.9%; p < 0.01), and brachytherapy (AAPC: -8.3%; p < 0.01). A steep interest was found in active surveillance (AS) (AAPC: +14.2%; p < 0.01) and focal therapy (AAPC: +27.5%; p < 0.01). When trends were compared before and after NCCN and USPSTF recommendations, a consistent decrease of all the treatment options was found, while interest in focal therapy and AS showed an augmented mean ARSV (+19.6 and +31.6, respectively). CONCLUSIONS: People are increasingly searching the Internet for PCa treatment options. A parallel decrease of interest was found for the nonmonitoring treatments, except for focal therapy, while an important growth of appeal has been recorded for AS. Understanding people inquisitiveness together with their degree of knowledge could be supportive to guiding counselling in the decision-making process and putting effort in certifying patient information. PATIENT SUMMARY: In the era of digital data, patients are increasingly searching the Internet for prostate cancer (PCa) treatment options. To safeguard patients' knowledge, it is mandatory to understand how people seek healthcare information, guaranteeing certified and evidence-based information pertaining to PCa treatments options.

Multiple stones in neobladder: Case report and literature review.

INTRODUCTION: Neobladder urolithiasis is a rare but important long-term complication of orthotopic urinary diversion. It may be asymptomatic and can be discovered as an incidental finding on a radiological investigation. However, when symptoms occur, they may include lower abdominal pain, dysuria, hematuria, and lower urinary tract symptoms. CASE DESCRIPTION: We report the case of a 63-year-old male patient with irritative lower urinary tract symptoms, lower abdominal fullness, urinary incontinence, fecaluria, and urinary loss from the left inguinal fold 12 years after a radical cystoprostatectomy with a orthotopic neobladder. Computed tomography scan and urethrocystography showed a distended pouch with multiple large stones, an enterovesical fistula, and neovesicocutaneous fistula. The fistulae were successfully managed conservatively with the placement of a Foley catheter. After 3 months, open cystolithotomy was performed and approximately 50 stones with dimensions varying from 5 mm to 5 cm, with a total weight of 890 g, were removed. After a 1-year follow-up, the patient did not report pain, urinary tract infections, or symptoms suggestive of fistula and imaging evaluation confirmed no recurrence of neobladder stones. CONCLUSION: Neobladder stones may present with various symptoms. Our patient had irritative lower urinary tract symptoms, lower abdominal fullness, urinary incontinence, fecaluria, and urinary loss from the left inguinal fold 12 years after a radical cystoprostatectomy with a orthotopic neobladder. Our experience demonstrates that open cystolithotomy is an effective intervention for the removal of large stones in neobladder.

A circulating miRNA assay as a first-line test for prostate cancer screening.

BACKGROUND: Prostate cancer (PCa) screening currently relies on prostate-specific antigen (PSA) testing and digital rectal examination. However, recent large-scale studies have questioned the long-term efficacy of these tests, and biomarkers that accurately identify PCa are needed. METHODS: We analysed the levels of circulating microRNAs (miRNAs) in patients with elevated PSA who were diagnosed with either localised PCa (n=36) or benign prostatic hyperplasia (BPH, n=31) upon biopsy. Real-time RT-PCR with Taqman probes was used to measure plasma levels of miRNAs. To circumvent problems associated with circulating miRNA quantitation, we computed the expression ratios of upregulated and downregulated miRNAs. RESULTS: The miR-106a/miR-130b and miR-106a/miR-223 ratios were significantly different between the biopsy-positive and BPH groups (P<0.0001), and yielded statistical power values that were >0.99. Both miRNA ratios were highly sensitive and more specific than PSA in discriminating localised PCa from BPH. Receiver operating characteristic curve analysis revealed area under curve values of 0.81 (miR-106a/miR-130b) and 0.77 (miR-106a/miR-223). CONCLUSIONS: Testing for circulating miR-106a/miR-130b and miR-106a/miR-223 ratios may reduce the costs and morbidity of unnecessary biopsies and is feasible for large-scale screening, as it requires measuring only three miRNAs.