Nam Cheol Park

An epidemiological study of enuresis in Korean children

Objective To estimate the prevalence of enuresis in children of elementary school age, to evaluate the impact of enuresis on these children and their parents, and to identify the methods and effectiveness of managing enuresis.

Treatment of premature ejaculation in the Asia-Pacific region: results from a phase III double-blind, parallel-group study of dapoxetine.

INTRODUCTION Dapoxetine is a short-acting selective serotonin reuptake inhibitor that was recently approved for the on-demand treatment of premature ejaculation (PE). AIM To evaluate the efficacy and safety of dapoxetine 30 mg and 60 mg on demand (prn) in men with PE from the Asia-Pacific region. METHODS This randomized, double-blind, parallel-group, placebo-controlled trial enrolled men who were 18 years or older; in a monogamous, heterosexual relationship for at least 6 months; met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision, criteria for PE for at least 6 months; and had an intravaginal ejaculatory latency time (IELT) of 2 minutes or less in at least 75% of sexual intercourse episodes. Subjects received placebo, dapoxetine 30 mg, or dapoxetine 60 mg prn (1-3 hours before intercourse) for 12 weeks. MAIN OUTCOME MEASURES Stopwatch-measured Average IELT, the Premature Ejaculation Profile (PEP), Clinical Global Impression (CGI) of change in PE, treatment-emergent adverse events (TEAEs). RESULTS Of the 1,067 subjects randomized, 858 completed the study. Mean Average IELT increased from approximately 1.1 minutes at baseline (across groups) to 2.4, 3.9, and 4.2 minutes with placebo, dapoxetine 30 mg, and dapoxetine 60 mg, respectively, and geometric mean Average IELT increased from approximately 0.9 minutes at baseline (across groups) to 1.8, 2.7, and 3.1 minutes, respectively (fold-increases of 2.0, 2.8, and 3.3, respectively). All PEP measures and the CGI of change were significantly improved with dapoxetine vs. placebo at study endpoint (P < or = 0.005 for all). The most common TEAEs with dapoxetine included nausea, dizziness, somnolence, headache, vomiting, diarrhea, and nasopharyngitis; TEAEs led to discontinuation in 0.3%, 1.7%, and 5.1% of subjects with placebo, dapoxetine 30 mg, and dapoxetine 60 mg, respectively. CONCLUSIONS Dapoxetine treatment significantly prolonged IELT and improved PEP measures and was generally well tolerated in men with PE in the Asia-Pacific region.

Standards for Clinical Trials in Male Sexual Dysfunctions

INTRODUCTION Clinical trials in male sexual dysfunction (MSD) are expanding. Consequently, there is a need for consensus standards in this area. AIM To develop an evidence-based, state-of-the-art consensus report on standards for clinical trials in MSD. METHODS A literature review was performed examining clinical trials in erectile dysfunction (ED), premature ejaculation (PE), delayed/absent ejaculation, libido disorders/loss of desire, hypogonadism, and Peyronies disease, focusing on publications published in the last 20 years. This manuscript represents the opinions of eight experts from seven countries developed in a consensus process. This document was presented for peer review and debate in a public forum and revisions were made based on recommendations of chairpersons to the International Consultation on Sexual Medicine. MAIN OUTCOME MEASURE Expert opinion was based on the grading of evidence-based medical literature, widespread internal committee discussion, public presentation, and debate. RESULTS According to experience and recent publications in dealing with clinical trials in sexual dysfunction, recommendations have been made for conducting trials in patients with ED, PE, delayed ejaculation, libido disorders, hypogonadism, and Peyronies disease. CONCLUSIONS It is important that future clinical trials are conducted using standards upon which investigators can rely when reading manuscripts or conducting new trials in this field.

Efficacy and Safety of Once-Daily Dosing of Udenafil in the Treatment of Erectile Dysfunction: Results of a Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

BACKGROUND A once-daily dosing regimen with a phosphodiesterase type 5 inhibitor is needed for the treatment of erectile dysfunction (ED), in part because of the behavioral complexities associated with sexual intimacy. Many patients prefer spontaneous rather than scheduled sexual activities or they anticipate frequent sexual encounters. The pharmacokinetic profiles of udenafil with a time of maximal concentration of 1.0-1.5h and a terminal half-life of 11-13 h make udenafil a good candidate for once-daily dosing. OBJECTIVE To evaluate the efficacy and safety of once-daily dosing of udenafil in the treatment of ED. DESIGN, SETTING, AND PARTICIPANTS This multicenter randomized double-blind, placebo-controlled, fix-dosed clinical trial involved 237 patients with ED. The subjects, who were treated with placebo or udenafil (25mg, 50mg, or 75 mg) once daily for 12 wk, were asked to complete the International Index of Erectile Function (IIEF), the Sexual Encounter Profile (SEP) diary, and the Global Assessment Questionnaire (GAQ) during the study. MEASUREMENTS The primary outcome parameter was the change from baseline for the IIEF erectile function domain (EFD) score. The secondary outcome parameters were SEP questions 2 and 3, the shift to normal rate (EFD ≥ 26), and the response to the GAQ. RESULTS AND LIMITATIONS Compared with placebo, patients who took 50mg or 75 mg of udenafil had a significantly improved IIEF-EFD score. Similar results were observed in comparing questions 2 and 3 in the SEP diary and the GAQ. Flushing was the most common treatment-related adverse event, which was transient and mild to moderate in severity. CONCLUSIONS Udenafil significantly improved erectile function among ED patients when administered in doses of 50mg or 75 mg once daily for 12 wk. Daily administration of udenafil (50mg) may be another treatment option for ED.

Silibinin polarizes Th1/Th2 immune responses through the inhibition of immunostimulatory function of dendritic cells.

Silibinin is the primary active compound in silymarin. It has been demonstrated to exert anti‐carcinogenic effects and hepato‐protective effects. However, the effects of silibinin on the maturation and immunostimulatory activities exhibited by dendritic cells (DCs) remain, for the most part, unknown. In this study, we have attempted to determine whether silibinin can influence surface molecule expression, dextran uptake, cytokine production, capacity to induce T‐cell differentiation, and the signaling pathways underlying these phenomena in murine bone marrow‐derived DCs. Silibinin was shown to significantly suppress the expression of CD80, CD86, MHC class I, and MHC class II in the DCs, and was also associated with impairments of LPS‐induced IL‐12 expression in the DCs. Silibinin‐treated DCs proved highly efficient with regard to Ag capture via mannose receptor‐mediated endocytosis. Silibinin also inhibited the LPS‐induced activation of MAPKs and the nuclear translocation of the NF‐κB p65 subunit. Additionally, silibinin‐treated DCs evidenced an impaired induction of Th1 response, and a normal cell‐mediated immune response. These findings provide new insight into the immunopharmacological functions of silibinin, especially with regard to their impact on the DCs. These findings expand our current understanding of the immunopharmacological functions of silibinin, and may prove useful in the development of therapeutic adjuvants for acute and chronic DC‐associated diseases. J. Cell. Physiol. 210: 385–397, 2007.

ORIGINAL RESEARCH—ED PHARMACOTHERAPY: Sildenafil Citrate 100 mg Starting Dose in Men with Erectile Dysfunction in an International, Double-Blind, Placebo-Controlled Study: Effect on the Sexual Experience and Reducing Feelings of Anxiety About the Next Intercourse Attempt

INTRODUCTION Sildenafil citrate 50 mg is the recommended starting dose for men with erectile dysfunction (ED); however, most men are later titrated to sildenafil 100 mg for improved efficacy. AIM Assess the tolerability and efficacy of sildenafil initiated at the 100-mg dose in men with ED. METHODS Men with ED (score < or =25 on the Erectile Function domain of the International Index of Erectile Function) who had received < or =6 total doses of a phosphodiesterase type 5 inhibitor and none within 4 weeks were randomized to 8 weeks of double-blind, placebo-controlled (DBPC), fixed-dose treatment (50 or 100 mg sildenafil or placebo) followed by 4 weeks of open-label flexible-dose sildenafil (50 or 100 mg). MAIN OUTCOME MEASURES Efficacy, tolerability, treatment satisfaction, and other end points were measured at baseline and/or the end of the double-blind and open-label phases and compared between placebo and sildenafil initiated at doses of 50 and 100 mg. RESULTS Improvements in DBPC patient-reported outcomes from baseline were statistically significant for both sildenafil 50 and 100 mg compared with placebo. At the end of DBPC treatment, 56% of men on the 100-mg dose felt no anxiety about the next intercourse attempt compared with 39% in the 50-mg group (odds ratio 2.03; P = 0.0197). Changes in functional scores from baseline were not statistically significant with the 100-mg dose compared with the 50-mg dose in the DBPC. Measures of treatment satisfaction and sexual experience significantly favored the 100-mg dose compared with the 50-mg dose in the DBPC. There was no increase in adverse events with the higher dose. CONCLUSIONS Sildenafil at 50 mg or 100 mg significantly improved erection quality, treatment satisfaction, anxiety levels, and the sexual experience compared with placebo during DBPC. Sildenafil 100 mg improved the sexual experience and treatment satisfaction, and reduced feelings of anxiety compared with the 50-mg dose.

Efficacy and safety of avanafil for treating erectile dysfunction: results of a multicentre, randomized, double‐blind, placebo‐controlled trial

Study Type – Therapy (RCT)

Predictors of pain resolution after varicocelectomy for painful varicocele.

Varicocelectomy is a management option for patients with painful varicocele. In this study, we assessed the effectiveness of varicocelectomy for painful varicocele and examined the factors that might be predictive of outcome. All patients who underwent a varicocelectomy for pain between February 2007 and July 2009 were included. A review of patient medical records was conducted; patient age, body mass index (BMI), grade, location of the varicocele, testicular volume, duration and quality of the pain (dull, dragging, throbbing or sharp) and surgical technique (inguinal versus subinguinal) were documented. All parameters were compared with the resolution of pain (complete, partial or failure). We followed up on 53 of 104 patients (51.0%). Complete postoperative resolution of pain was reported by 28 patients (52.8%), whereas 22 (41.5%) reported partial resolution. Only three patients (5.7%) reported failure. No relationship was observed between postoperative pain resolution and age, BMI, grade of varicocele, location of varicocele, ipsilateral testicular hypotrophy, quality of pain or surgical technique. The duration of pain before surgery was the only factor that correlated with postoperative pain resolution (univariate, P=0.004; multivariate, P=0.002). Our results indicate that varicocelectomy is an effective treatment for painful varicocele in properly selected patients, and that duration of pain before surgery may be predictive of outcome.

Tadalafil Administered Once Daily for Treatment of Lower Urinary Tract Symptoms in Korean men with Benign Prostatic Hyperplasia: Results from a Placebo-Controlled Pilot Study Using Tamsulosin as an Active Control

Objectives: Assess the efficacy and safety of once‐daily tadalafil or tamsulosin versus placebo during 12 weeks on lower urinary tract symptoms (LUTS) in Korean men with benign prostatic hyperplasia (BPH).

ORIGINAL RESEARCH—ED PHARMACOTHERAPY: The Efficacy and Safety of Udenafil [Zydena] for the Treatment of Erectile Dysfunction in Hypertensive Men Taking Concomitant Antihypertensive Agents

INTRODUCTION Erectile dysfunction (ED) and hypertension are frequent comorbid conditions. The vasodilating properties of type 5 phosphodiesterase inhibitor (PDE5I) are the major concerns for the treatment of ED patients on antihypertensive medications. AIM To evaluate the efficacy and safety of Udenafil [Zydena] (Dong-A, Seoul, Korea), a newly developed PDE5I, for the treatment of ED patients on antihypertensive medication. METHODS It was a multicentered, randomized, double-blind, placebo-controlled, fix-dosed clinical trial among 165 ED patients receiving antihypertensive medications. The subjects treated with placebo, 100 mg or 200 mg of Udenafil for 12 weeks were asked to complete the Sexual Encounter Profile (SEP) diary, the International Index of Erectile Function (IIEF), and the Global Assessment Question (GAQ) during the study period. MAIN OUTCOME MEASURES Primary parameter: the change from baseline for IIEF erectile function domain (EFD) score; Secondary parameters: the IIEF Question 3 and 4, SEP Question 2 and 3, the rate of achieving normal erectile function (EFD > or = 26) and the response to GAQ. RESULTS Compared to placebo, patients receiving both doses of Udenafil showed significantly improved the IIEF-EFD score. The least squares means for the change from baseline in IIEF-EFD scores were 8.4 and 9.8 for 100 mg and 200 mg Udenafil groups, respectively; those values were significantly higher than that of placebo (2.4, P < 0.0001). Similar results were observed in the comparison of Q3 and Q4 of IIEF, SEP diary and GAQ. Headache and flushing were the most common treatment-emergent adverse events, which were transient and mild-to-moderate in nature. No parameters of efficacy and safety were affected among the subsets stratified according to either the number of antihypertensive medication received or the previous experience of PDE5Is treatment. CONCLUSION Udenafil significantly improved erectile function among ED patients with hypertensive symptom treated with concomitant antihypertensive medication. The treatment did not increase the frequency or severity of adverse events.