Efficacy and safety of desmopressin orally disintegrating tablets 25 and 50 µg in male patients with nocturia: A Japanese real-world multicenter clinical study.

OBJECTIVES: To clarify Japanese real-world clinical data on the use of desmopressin 25 and 50 µg orally disintegrating tablets (ODT) for male patients with nocturia and evaluate the predictive factors to improve nighttime frequency. METHODS: We retrospectively accumulated real-world clinical data from 27 institutions in Japan. Male patients with two or more episodes of nocturia who received desmopressin ODT for nocturnal polyuria (NP) from 2019 through 2021 were included. The primary endpoint was the change of nighttime frequency until 3 months after desmopressin administration. The secondary endpoints were to clarify the persistence rate, adverse events, and predictive factors of decreasing nighttime frequency. RESULTS: A total of 118 patients were eligible to participate in this study. The persistence rate of desmopressin on the Kaplan-Meier curve at week 12 was 51.3. The reason for discontinuation was mainly the occurrence of adverse events in 67 patients (56.8%), particularly hyponatremia in 7 patients (5.9%). Nighttime frequencies at baseline, - 1 month and 1 - 3 months after desmopressin administration were 4.1 ± 1.3, 2.9 ± 1.4 (P < .01), and 2.6 ± 1.3 (P < .01), respectively. The mean nighttime urine volume voided at baseline was significantly larger in patients whose nighttime frequency decreased by two or more times than in those with a decrease of less than two times. CONCLUSIONS: Desmopressin 25 and 50 µg ODT treatments are feasible for male patients with NP in Japanese real-world clinical practice. Patients with higher voided volumes, particularly in the nighttime, may have great benefit from desmopressin.

Silodosin as second-line α-blocker monotherapy in patients with benign prostatic hyperplasia: A prospective observational study.

OBJECTIVE: To assess the efficacy of silodosin as second-line α-blocker monotherapy in patients with lower urinary tract symptoms as a result of benign prostatic hyperplasia. METHODS: Men who were given an α-blocker other than silodosin for ≥8 weeks, aged ≥50 years, had a total International Prostate Symptom Score ≥13 and quality of life index ≥4 were enrolled. After treatment with 8 mg/day silodosin for 8 weeks, symptoms and treatment satisfaction were assessed. If the patients still complained and hoped for readministration of the first-line α-blocker, the previous medication was administered again for 8 weeks in the case of persisting symptoms, and efficacy was again evaluated. RESULTS: A total of 73 patients were enrolled and analyzed at 8 weeks. Silodosin administration significantly improved the International Prostate Symptom Score and Overactive Bladder Symptom Score. The quality of life index was improved by at least 1 point in 49.3% patients, and its mean change was significantly greater in the group with previous naftopidil treatment than in those with tamsulosin. A total of 59 patients hoped to continue silodosin, and 13 requested administration of the first-line α-blocker. Previously taking naftopidil and having a shorter duration of prior α-blocker treatment at baseline were associated with silodosin continuation. Although prior α-blocker readministration in the 13 patients did not show significant efficacy, six preferred to continue the previous α-blocker. CONCLUSIONS: Silodosin represents an effective second-line α-blocker monotherapy, even in those who still have moderate lower urinary tract symptoms.

Three-year outcome analysis of alpha 1-blocker naftopidil for patients with benign prostatic hyperplasia in a prospective multicenter study in Japan.

PURPOSE: Our aim was to prospectively analyze the 3-year outcomes of naftopidil treatment for patients with benign prostatic hyperplasia (BPH), including those who dropped out during follow-up and had retreatment for BPH after termination of the drug within 3 years. PATIENTS AND METHODS: Naftopidil, 50 mg/d or 75 mg/d, was given to 117 patients having BPH aged 50 years and older who had international prostate symptom scores (IPSS) ≥8. They were prospectively followed for 3 years with periodic evaluation. If naftopidil was terminated, the reason was determined. For patients with termination, an outcome survey was done to evaluate the status of retreatment for BPH at 3 years. RESULTS: Twenty-five patients (21.4%) continued the same medication for 3 years. The total IPSS, quality of life index, BPH problem index, and maximum flow rate were significantly improved during 3 years. Treatment failure defined as symptomatic progression (an increase in the IPSS of ≥4 points compared to the baseline value), development of acute urinary retention, conversion to other α1-blockers, add-on of a 5α-reductase inhibitor, or conversion to surgery was observed in 41 patients (35.0%). In the univariate analysis, age, prostate volume, and serum prostate-specific antigen were predictors of treatment failure. Of the 50 patients who discontinued naftopidil during the follow-up, only 13 (26%) patients reported that they needed retreatment with α1-blockers and/or surgery within 3 years. CONCLUSION: Long-term efficacy of naftopidil was observed, although older age, increased prostate volume, and elevated prostate-specific antigen at baseline were highly likely to result in treatment failure. Even after termination for various reasons, only a small portion of the patients needed retreatment for BPH within 3 years.

A randomized controlled study of the efficacy of tamsulosin monotherapy and its combination with mirabegron for overactive bladder induced by benign prostatic obstruction.

PURPOSE: We evaluated the efficacy and safety of add-on treatment with a ß3-adrenoceptor agonist (mirabegron) for overactive bladder symptoms remaining after α1-blocker (tamsulosin) treatment in men with benign prostatic obstruction. MATERIALS AND METHODS: Patients with benign prostatic obstruction with urinary urgency at least once per week and a total OABSS of 3 or more points after 8 or more weeks of treatment with tamsulosin were enrolled in the study. They were randomly allocated to receive 0.2 mg tamsulosin daily or 0.2 mg tamsulosin and 50 mg mirabegron daily for 8 weeks. The primary end point was change in total OABSS. Safety assessments included change in post-void residual urine volume and adverse events. RESULTS: From January 2012 through September 2013 a total of 94 patients were randomized. Of these patients 76 completed the protocol treatment. In the full analysis set the change in total OABSS during the treatment period was significantly greater in the combination group than in the monotherapy group (-2.21 vs -0.87, p=0.012). The changes in scores for urinary urgency, daytime frequency, International Prostate Symptom Score storage symptom subscore and quality of life index at 8 weeks were significantly greater in the combination group. The change in post-void residual urine volume was significantly greater in the combination group. Although 6 patients experienced adverse events in the combination group, urinary retention was observed in only 1 patient. CONCLUSIONS: Combined tamsulosin and mirabegron treatment is effective and safe for patients with benign prostatic obstruction who have overactive bladder symptoms after tamsulosin monotherapy.

Clinical Efficacy of a Single Two Gram Dose of Azithromycin Extended Release for Male Patients with Urethritis.

To clarify the clinical efficacy of a single oral 2 g dose of azithromycin extended-release for heterosexual male patients with urethritis, and the current antimicrobial sensitivity of Neisseria gonorrhoeae to azithromycin, a prospective clinical trial was conducted from 2011-2013. In patients with gonococcal urethritis, the eradication rate was 90.9% (30 of 33). The susceptibility rates of isolated Neisseria gonorrhoeae strains to ceftriaxone, spectinomycin, cefixime and azithromycin were 100%, 100%, 95.3% (41/43) and 37.2% (16/43), respectively. In the patients with nongonococcal urethritis, the eradication rate was 90.0% (45 of 50). The microbiological eradication rates for the pathogens were 90.9% (30/33) for Neisseria gonorrhoeae, 91.5% (43/47) for Chlamydia trachomatis, 71.4% (5/7) for Mycoplasma genitalium, and 100% (13/13) for Ureaplasma urealyticum. The main adverse event was diarrhea and its manifestation rate was 35.2% (32 of 120). The symptom of diarrhea was mostly temporary and resolved spontaneously. The conclusion was that the treatment regimen with a single oral 2 g dose of azithromycin extended-release would be effective for patients with urethritis. However, the antimicrobial susceptibilities of Neisseria gonorrhoeae and Mycoplasma genitalium should be carefully monitored because of possible treatment failure.

Antimicrobial susceptibility and penicillin-binding protein 1 and 2 mutations in Neisseria gonorrhoeae isolated from male urethritis in Sapporo, Japan.

The spread of antimicrobial-resistant Neisseria gonorrhoeae worldwide is a critical issue in the control of sexually transmitted infections. The purpose of this study was to clarify recent trends in the susceptibility of N. gonorrhoeae to various antimicrobial agents and to compare these data with our previous data. Minimum inhibitory concentrations (MICs) of various antimicrobial agents were determined in N. gonorrhoeae strains clinically isolated from male gonococcal urethritis. In addition, amino acid sequencing of penicillin-binding protein (PBP) 2, encoded by the penA gene, was analyzed so that genetic analysis of mosaic PBP 2 could clarify the susceptibility of the strains to cefixime and other cephalosporins. The susceptibility rate for ceftriaxone, cefodizime, and spectinomycin, agents whose use is recommended by the guideline of the Japanese Society of Sexually Transmitted Infections (JSSTI), was 100 %. The susceptibility rates of the strains to penicillin G and ciprofloxacin were lower than those in previous reports. Mosaic PBP 2 structures were detected in 51.9 % of the strains and the MICs of the strains with the mosaic PBP 2 to cefixime were much higher than those of the strains without the mosaic PBP 2. In the clinical situation, the treatment regimen recommended by the JSSTI remains appropriate; however, the susceptibility to cephalosporins should be intensively surveyed because strains with mosaic PBP 2 were commonly detected.

The efficacy and safety of propiverine hydrochloride in patients with overactive bladder symptoms who poorly responded to previous anticholinergic agents.

Objectives. To prospectively examine the efficacy and safety of propiverine hydrochloride in patients with overactive bladder (OAB) symptoms who poorly responded to previous treatment with solifenacin, tolterodine or imidafenacin. Methods. Patients aged ≥20 with persisting OAB symptoms (≥6 in OAB symptom score (OABSS)) even after at least 4-week treatment using solifenacin, tolterodine or imidafenacin were enrolled. Propiverine 20 mg/day was administered for 12 weeks to 70 patients who desired the further improvement of OAB symptoms and 3 who had intolerable adverse events of previous drugs. The OABSS and postvoid residual urine volume (PVR) were determined before and at 4 and 12 weeks of treatment. Results. Of 73 patients enrolled (29 males and 44 females, median age 71 years), 52 completed the protocol treatment. The OABSS was significantly improved by propiverine treatment (9.0 at baseline, 6.2 at 4 weeks, 6.3 at 12 weeks (P < 0.001)). The scores of OAB symptoms (nighttime frequency, urgency and urge incontinence) except daytime frequency also improved significantly. No increase in PVR was observed. The most frequent adverse event was dry mouth (13.7%), followed by constipation (6.8%). Conclusions. Propiverine is useful to improve OAB for patients who poorly respond to solifenacin, tolterodine or imidafenacin.

Management for males whose female partners are diagnosed with genital chlamydial infection.

The purpose of this study was to investigate the infection rate of asymptomatic men whose female sexual partners were diagnosed as having genital chlamydial infection and discuss the management for them. The subjects were asymptomatic men whose female sexual partners were diagnosed with genital chlamydial infection at other obstetric and gynecological clinics. Microscopic findings of urinary sediment and the results of a nucleic acid amplification test of the first-voided urine specimen were retrospectively examined in those men who visited our clinics. A total of 267 men were included and analyzed. The infection rate for urinary Chlamydia trachomatis in asymptomatic men was 36.3% (97 of 267). In the analysis of urinary sediment, 35 of the 267 (13.1%) had pyuria and 82.9% (29 of 35) in the men with pyuria were positive for urinary C. trachomatis in. Even in men without pyuria, the urinary C. trachomatis-positive rate was 29.3% (68 of 232). When such men have pyuria in the clinic, prompt treatment is the appropriate approach. If the men are without pyuria, testing for urinary C. trachomatis should be performed. Prompt treatment before doing any clinical evaluation can be an option in couples with trouble.

Clinical efficacy of levofloxacin 500 mg once daily for 7 days for patients with non-gonococcal urethritis.

To confirm the efficacy of the treatment regimen with oral levofloxacin (LVFX) 500 mg once daily for 7 days for patients with non-gonococcal urethritis (NGU), we evaluated the microbiological and clinical outcomes of the regimen in those patients. We finally evaluated 53 patients with symptomatic NGU and 5 patients with asymptomatic NGU. As a result of microbiological examinations, 19 of the symptomatic patients were diagnosed as having non-gonococcal chlamydial urethritis (NGCU); 13 had non-gonococcal non-chlamydial urethritis (NGNCU), and 21 had urethritis without any microbial detection. Five of the asymptomatic patients were diagnosed as having NGCU. Microbiological cure was achieved in 91% of the 32 patients with symptomatic NGU and in 80% of the 5 patients with asymptomatic NGCU. Clinical cure was obtained in 92% of the 53 patients with symptomatic NGU. The microbiological eradication rate for Chlamydia trachomatis was 92% in 24 patients. As for other organisms, the microbiological eradication rate for Mycoplasma genitalium was 60% in 5 patients and that for Ureaplasma urealyticum was 100% in 10. The microbiological and clinical efficacy of oral LVFX 500 mg once daily for 7 days for the patients with NGU was the same for the azithromycin (AZM) 1,000 mg single dose that we previously reported. The eradication rates of C. trachomatis and U. urealyticum in the treatment regimen with LVFX 500 mg were high enough in the clinical setting; however, for M. genitalium, the rate was relatively inferior to that with AZM.

Ejaculatory disorders caused by alpha-1 blockers for patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia: comparison of naftopidil and tamsulosin in a randomized multicenter study.

INTRODUCTION: To investigate the incidence of ejaculatory disorders caused by naftopidil and tamsulosin in patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Ninety-five patients with LUTS/BPH who had International Prostate Symptom Scores (IPSS) of 8 or more were randomly assigned to receive naftopidil (50 mg/day, n = 48) or tamsulosin (0.2 mg/day, n = 47). Before and 12 weeks after treatment, a questionnaire was used to evaluate ejaculation. RESULTS: Among men who had sexual activity during the 12 weeks, the proportion who reported an abnormal feeling on ejaculation was higher in the tamsulosin group (16.7%) than in the naftopidil group (7.4%), although the difference was not significant (p = 0.402). The proportion of men who reported reduced ejaculatory volume after treatment was significantly higher in the tamsulosin group (96.0%) than in the naftopidil group (73.1%, p = 0.0496). On the other hand, the improvements in IPSS and the quality of life index were significantly higher in the tamsulosin group than in the naftopidil group. CONCLUSIONS: Tamsulosin may cause a higher incidence of ejaculatory disorders than naftopidil, although the efficacy of 0.2 mg tamsulosin may be better than that of 50 mg naftopidil.

Clinical efficacy of azithromycin for male nongonococcal urethritis.

The aim of this study was to confirm the clinical efficacy of a single-dose azithromycin (AZM) regimen (1000 mg) for patients with nongonococcal urethritis in real-life practice. The study finally evaluated 55 patients, 42 who were symptomatic and 13 who were asymptomatic, after excluding 40 who visited clinics only once. Sixteen of the symptomatic patients were diagnosed as having nongonococcal chlamydial urethritis, 7 as having nongonococcal nonchlamydial urethritis, and 19 as having urethritis without any microbial detection. Chlamydia trachomatis was detected in 11 asymptomatic patients, Mycoplasma genitalium in 1, and Ureaplasma urealyticum in 1. Of the patients who were microbiologically evaluated before and after single-dose AZM, microbiological cure was achieved in 87% (20/23) of those with symptomatic nongonococcal urethritis and in 100% (13/13) of those with asymptomatic nongonococcal urethritis. The clinical cure rate was 86% for the 42 symptomatic patients with detectable and undetectable pathogens. There were adverse events in 5 (9%) patients but they were commonly mild and self-limited. In conclusion, the single-dose AZM regimen was well tolerated and eradicated the estimated and potential pathogens of nongonococcal urethritis.

Gatifloxacin treatment for chronic prostatitis: a prospective multicenter clinical trial.

Antimicrobial treatment is usually used for chronic prostatitis. However, the efficacy of such treatment has not been fully evaluated. We conducted a study to evaluate the efficacy of gatifloxacin for patients with chronic prostatitis using the Japanese version of the National Institutes of Health Chronic Prostatitis Symptom Index (JPN-NIH CPSI). The study included 46 patients for final analysis. Patients who were younger than 65 years of age were treated with 200 mg gatifloxacin twice daily, and those who were 65 years and older were treated with 100 mg gatifloxacin twice daily, for 4-8 weeks. The study consisted of 10 patients in category II, 13 in category IIIA, 11 in category IIIB, and 12 who were unclassified. The gatifloxacin treatment resulted in significant reductions in the scores on the JPN-NIH CPSI. Of the total number of patients, 58.1% and 27.9% were 25% and 50% responders, respectively, 4 weeks after treatment, and these figures improved to 66.7% and 33.3%, respectively, 8 weeks after treatment. No significant difference was found in the changes in symptom scores between Category II and Category IIIA/IIIB groups. In conclusion, gatifloxacin treatment improved the symptoms in patients with chronic bacterial and nonbacterial prostatitis. This study is the first in this country to evaluate the efficacy of antimicrobial treatment for chronic prostatitis by using the NIH CPSI.

Bone scanning--who needs it among patients with newly diagnosed prostate cancer?

BACKGROUND: We evaluated the relationship between serum PSA and clinical variables to eliminate bone scanning in patients with prostate cancer having a low probability of bone metastasis. METHODS: The study included 366 patients with newly diagnosed prostate cancer between 1999 and 2005. Bone metastasis was studied for its correlation with various clinical and pathological variables in these patients. RESULTS: Bone metastasis was found in 28 (7.7%) of 366 patients. Fourteen patients had skeletal symptoms related to bone metastasis. The risk for bone metastases increased considerably with increases of PSA level, clinical T stage and Gleason score. The metastasis was not found in 161 patients with serum PSA concentration of 10 ng/ml or lower. In 95 patients with the concentration between 10 and 20 ng/ml only two had the metastasis. These two patients had T2 disease and Gleason scores of 7 or greater. In 204 patients with clinical stage T1 disease, one (0.5%) had the metastasis. In 117 patients with Gleason scores of 6 or less, the metastasis was found in two (1.7%). CONCLUSIONS: For patients with serum PSA levels of 10 ng/ml or lower, bone scanning may be eliminated because of the negligible risk of bone metastases. In addition, scanning may not be necessary for those with PSA levels between 10 and 20 ng/ml, when they have T1 disease and Gleason scores of 6 or lower.

Detection of human papillomavirus DNA on the external genitalia of healthy men and male patients with urethritis.

BACKGROUND: Only a few studies have been done involving detection of human papillomavirus (HPV) DNA on the external genitalia of men without genital warts, although many have been done for women. We conducted HPV DNA detection among healthy male volunteers and men with urethritis, both having no visible lesions on their external genitalia. GOAL: The goal of the study was to determine the detection rate of HPV DNA in volunteers and patients with urethritis and to determine risk factor(s) for positive DNA. STUDY DESIGN: This was a prospective clinical study. RESULTS: HPV DNA was found in 1.3% of 75 volunteers and in 18.5% of 130 patients with urethritis. DNA of a high-intermediate oncogenic risk was more predominant than the low-risk type. Among various risk factors, only a history of STD was a significant factor for the positive detection of HPV DNA in multiple regression analysis. CONCLUSION: HPV DNA was found in patients with urethritis more frequently than in volunteers, probably because the former had higher sexual activity.

Efficacy of an RNA detection test kit in the diagnosis of genital chlamydial infection.

A nucleic acid amplification method based on DNA detection, the current standard method for the diagnosis of genital infection by Chlamydia trachomatis, has been shown to potentially yield false-positive results after treatment in the clinical setting. RNA detection methods are more appropriate because viable organisms have multiple RNA copies that are surely detected by the method. In this study, we evaluated the efficacy of a new RNA detection test kit, the VIDAS PROBE CT test, in the diagnosis of genital chlamydial infection. For comparison, the standard DNA detection method, Amplicor STD-I, was also used in the study. First voided-urine samples and urethral smears from male patients with urethritis, and first voided-urine samples and cervical smears from female patients with cervicitis served as samples for the detection of C. trachomatis. Of the 60 first voided-urine samples from male patients, 21 were positive and 39 negative with the VIDAS PROBE CT test. Amplicor STD-I achieved exactly the same result. In female patients with cervicitis, the two test kits produced the same result, with 2 positive cervical smears and 38 negative. These results suggest that the VIDAS PROBE CT test is as efficient as Amplicor STD-I in the detection of C. trachomatis. While studies including a greater number of patients will be needed for revealing the unique advantages of the new RNA detection test kit, VIDAS PROBE CT, we concluded from the current study that the test may be clinically useful in the diagnosis of genital chlamydial infection.