Telemedicine Utilization in the COVID-19 Era: Patterns of Care in Community Urology Practice.

INTRODUCTION: The acute phase of the COVID-19 pandemic disrupted ambulatory care in the US, and in response telemedicine was adopted rapidly but unevenly across specialties and time. This study examines the utilization of telemedicine in the specialty of urology across a 3-year period (before, during, and after the onset of the pandemic) with the objective of describing patterns, costs, and trends in telemedicine utilization in the specialty. METHODS: The study data were drawn from the adjudicated claims of 1726 providers in 41 independent (privately owned) practices across the US from March 2019 to February 2022. Encounters were indexed to providers to allow for comparisons of utilization across time. Telehealth adoption was defined as the percentage of encounters eligible for reimbursement by telehealth actually conducted by telehealth. RESULTS: A total of 3,630,474 individual patients and 16,130,444 unique encounters were included in our analysis. Telehealth-eligible (evaluation and management) encounters declined sharply from a prepandemic baseline of 262 per provider per month (pppm) to a nadir of 164 pppm in April 2020 (acute phase), but quickly rebounded to 264 pppm by June 2020 (postacute phase). Telehealth adoption among urology providers in this study was 0% prior to March 2020, peaked at 46% in April 2020, and then declined rapidly in the months afterward. CONCLUSIONS: Telehealth adoption in urology spiked abruptly during the acute phase of the pandemic before declining to a low but stable level above prepandemic baseline. These findings may have implications for the broader role of telemedicine in the delivery of urologic care.

Surgical Stone Treatment: Patterns May Predict Performance on Episode-based Cost Measure in the Quality Payment Program.

INTRODUCTION: The Renal or Ureteral Stone Surgical Treatment Episode-based Measure in the Quality Payment Program evaluates clinicians' cost to Medicare for beneficiaries who receive surgical treatment for stones. The measure score is calculated from Medicare claims according to a complex methodology. This paper seeks to describe the stone treatment patterns of urologists and establish benchmarks for 2 surrogate measures-preoperative stenting and postoperative infection-which may predict clinician performance on the episode cost-based measure. METHODS: The study data were drawn from the adjudicated claims of 960 providers who performed at least 30 surgical stone treatments between January 1, 2020, and June 30, 2022. To allow for the correlation of procedures performed by the same providers, generalized estimating equations logistic regression models were used to evaluate the rate of preoperative stenting and postoperative infection. RESULTS: A total of 185,076 surgical episodes (113,799 [61.5%] ureteroscopy, 63,931 [34.5%] extracorporeal shock wave lithotripsy, and 7,346 [4.0%] percutaneous nephrolithotripsy) were identified over the study period. Preoperative stenting was performed in 35,550 episodes (19.2%) and postoperative infection was documented in 13,114 episodes (7.1%). Preoperative stenting and postoperative infection were significantly more common in patients who were female (adjusted OR 1.42, 1.38), in those undergoing ureteroscopy vs extracorporeal shock wave lithotripsy (adjusted OR 3.24, 1.66), and in patients on Medicare vs commercial insurance (adjusted OR 1.19, 1.17). CONCLUSIONS: This large study of surgical stone treatments documents rates of events and associated attributes of patients that may increase episode cost and be relevant to urologists participating in the Quality Payment Program.

An Evaluation of Sexual Function in the Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia in Men Treated with the Temporarily Implanted Nitinol Device.

Purpose: To document the effect of the temporarily implanted nitinol device (iTind; Medi-Tate Ltd, Israel) on sexual function from a multicenter, randomized, single-blinded, sham-controlled trial. Materials and Methods: Men were randomized 2:1 between iTind and sham procedure arms. The iTind was placed for 5-7 days and an 18F Foley catheter was inserted and removed for the iTind and sham group, respectively. Patients were assessed at baseline, 3, and 12 months postoperatively using the Sexual Health Inventory for Men (SHIM) and International Index of Erectile Function (IIEF). Unblinding occurred at 3 months. Results: We studied 185 men with a mean age of 61.1 ± 6.5 years. There was no difference in SHIM or total IIEF between iTind and sham at 3 months or in the iTind arm at 12 months compared with baseline. Men in the iTind arm without erectile dysfunction at baseline showed an improvement in total IIEF score of +6.07 ± 21.17 points (p = 0.034) at 12 months, in addition to an improvement in ejaculatory function. SHIM scores remained unchanged in all groups, regardless of age, prostate volume, or baseline erectile function. Conclusion: No changes were observed in sexual and ejaculatory function of patients with iTind regardless of a man's age, prostate volume, and baseline sexual function. Clinicaltrials.gov: NCT02506465.

Urinary Analysis of FGFR3 and TERT Gene Mutations Enhances Performance of Cxbladder Tests and Improves Patient Risk Stratification.

PURPOSE: Cxbladder tests are urinary biomarker tests for detection of urothelial carcinoma. We developed enhanced Cxbladder tests that incorporate DNA analysis of 6 single nucleotide polymorphisms for the FGFR3 and TERT genes, in addition to the current 5 mRNA biomarkers and clinical risk factors. MATERIALS AND METHODS: Two multicenter, prospective studies were undertaken in: (1) U.S. patients with gross hematuria aged ≥18 years and (2) Singaporean patients with gross hematuria or microhematuria aged >21 years. All patients provided a midstream urine sample and underwent cystoscopy. Samples were retrospectively analyzed using enhanced Cxbladder-Triage (risk stratifies patients), enhanced Cxbladder-Detect (risk stratifies patients and detects positive patients), and the combination enhanced Cxbladder-Triage × Cxbladder-Detect. RESULTS: In the pooled cohort (N=804; gross hematuria: n=484, microhematuria: n=320), enhanced Cxbladder-Detect had a sensitivity of 97% (95% CI 89%-100%), specificity of 90% (95% CI 88%-92%), and negative predictive value of 99.7% (95% CI 99%-100%) for detection of urothelial carcinoma. Overall, 83% of patients were enhanced Cxbladder-Detect-negative (ie, needed no further work-up). Of 133 enhanced Cxbladder-Detect-positive patients, 59 had a confirmed tumor, of which 19 were low-grade noninvasive papillary carcinoma or papillary urothelial neoplasm of low malignant potential. In total, 40 tumors were high-grade Ta, T1-T4, Tis, including concomitant carcinoma in situ. Of the 74 patients with normal cystoscopy, 41 were positive by single nucleotide polymorphism analysis. Enhanced Cxbladder-Triage and enhanced Cxbladder-Detect had significantly better specificity than the first-generation Cxbladder tests (P < .001). CONCLUSIONS: This study in ethnically diverse patients with hematuria showed the analytical validity of the enhanced Cxbladder tests.

IL-15 Superagonist NAI in BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer.

BACKGROUND: Patients with Bacillus Calmette­Guérin (BCG)­unresponsive non­muscle-invasive bladder cancer (NMIBC) have limited treatment options. The immune cell­activating interleukin-15 (IL-15) superagonist Nogapendekin alfa inbakicept (NAI), also known as N-803, may act synergistically with BCG to elicit durable complete responses (CRs) in this patient population. METHODS: In this open-label, multicenter study, patients with BCG-unresponsive bladder carcinoma in situ (CIS) with or without Ta/T1 papillary disease were treated with intravesical NAI plus BCG (cohort A) or NAI alone (cohort C). Patients with BCG-unresponsive high-grade Ta/T1 papillary NMIBC also received NAI plus BCG (cohort B). The primary end point was the incidence of CR at the 3- or 6-month assessment visit for cohorts A and C, and the disease-free survival (DFS) rate at 12 months for cohort B. Durability, cystectomy avoidance, progression-free survival, disease-specific survival (DSS), and overall survival were secondary end points for cohort A. RESULTS: In cohort A, CR was achieved in 58 (71%) of 82 patients (95% confidence interval [CI]=59.6 to 80.3; median follow-up, 23.9 months), with a median duration of 26.6 months (95% CI=9.9 months to [upper bound not reached]). At 24 months in patients with CR, the Kaplan­Meier estimated probability of avoiding cystectomy and of DSS was 89.2% and 100%, respectively. In cohort B (n=72), the Kaplan­Meier estimated DFS rate was 55.4% (95% CI=42.0% to 66.8%) at 12 months, with median DFS of 19.3 months (95% CI=7.4 months to [upper bound not reached]). Most treatment-emergent adverse events for patients receiving BCG plus NAI were grade 1 to 2 (86%); three grade 3 immune-related treatment-emergent adverse events occurred. CONCLUSIONS: In patients with BCG-unresponsive bladder carcinoma in situ and papillary NMIBC treated with BCG and the novel agent NAI, CRs were achieved with a persistence of effect, cystectomy avoidance, and 100% bladder cancer­specific survival at 24 months. The study is ongoing, with an estimated target enrollment of 200 participants (Funded by ImmunityBio.)

Clinical Research 2021.

Clinical research is of great benefit to patients and rewarding to clinicians. Clinical research in the United States is highly regulated. There are significant penalties for violating protocols. Clinical research requires a good infrastructure in each practice.

The iTind Temporarily Implanted Nitinol Device for the Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia: A Multicenter, Randomized, Controlled Trial.

OBJECTIVE: To report the results of a multicenter, randomized, controlled trial with a temporarily implanted nitinol device (iTind; Medi-Tate Ltd, Hadera, Israel) compared to sham for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. MATERIALS AND METHODS: Men 50 years or older were randomized 2:1 between iTind and sham procedure arms. A self-expanding, temporary nitinol device was placed for 5-7 days and an 18F Foley catheter was inserted and removed for the iTind and sham group, respectively. Patients were assessed at baseline, 1.5, 3, and 12 months postoperatively using the IPSS, peak urinary flow rate, residual urine, quality of life, and the International Index of Erectile Function. Unblinding occurred at 3 months. RESULTS: A total of 175 men (mean age 61.1 ± 6.5) participated (118 iTind vs 57 sham). A total of 78.6% of patients in the iTind arm showed a reduction of ≥3 points in IPSS, vs 60% of patients in the control arm at 3 months. At 12 months, the iTind group reported a 9.25 decrease in IPSS (P< .0001), a 3.52ml/s increase in peak urinary flow rate (P < .0001) and a 1.9-point reduction in quality of life (P < .0001). Adverse events were typically mild and transient, most Clavien-Dindo grade I or II, in 38.1% of patients in the iTind arm and 17.5% in the control arm. No de novo ejaculatory or erectile dysfunction occurred. CONCLUSION: Treatment with the second-generation iTind provided rapid and sustained improvement in lower urinary tract symptoms for the study period while preserving sexual function.

A 17-gene Panel for Prediction of Adverse Prostate Cancer Pathologic Features: Prospective Clinical Validation and Utility.

OBJECTIVE: To validate the 17-gene Oncotype DX Genomic Prostate Score (GPS) biopsy-based gene expression assay as a predictor of adverse pathology (AP, Gleason score [pGS] ≥4+3and/or ≥pT3) in a prospectively enrolled cohort. METHODS: Between July 2014 and September 2015, 1200 men with very low-, low-, and favorable intermediate-risk prostate cancer enrolled in a multi-institutional prospective study of the GPS assay (NCT03502213). The subset who proceeded to immediate radical prostatectomy (RP) after GPS testing was included in a prespecified subanalysis of GPS on biopsy and its association with surgical AP on RP using logistic regression and receiver operating characteristic curves. The effect of GPS testing on physicians' and patients' attitudes about decision making was assessed with the Decisional Conflict Scale. RESULTS: One hundred fourteen patients (treated by 59 physicians from 19 sites) elected RP and 40 (35%) had AP. GPS result was a significant predictor of AP (odds ratio per 20 GPS units [OR/20 units]: 2.2; 95% CI 1.2-4.1; P = .008) in univariable analysis and remained significant after adjustment for biopsy Gleason score, clinical T-stage, and logPSA (OR/20 units: 1.9; 95% CI 1.0-3.8; P = .04), or NCCN risk group (OR/20 units: 2.0; 95% CI 1.1-3.7; P = .02). Mean pre-GPS Decisional Conflict Scale score was 27 (95% CI 24-31), which improved significantly after GPS testing to 14 (95% CI 11-17) (P < .001). CONCLUSION: In this real-world multi-institutional study, the GPS assay was prospectively confirmed as an independent predictor of AP at surgery. GPS testing was associated with reduced patient decisional conflict.

Clinical comparison of noninvasive urine tests for ruling out recurrent urothelial carcinoma.

OBJECTIVE: Patients with urothelial carcinoma (UC) undergo rigorous surveillance for recurrence. Noninvasive urine tests are not currently recommended by guideline panels owing to insufficient clinical benefit. The objective of this study was to prospectively compare the performance of the Cxbladder Monitor test to other commonly available urine markers and cytology for surveillance of patients with UC. METHODS AND MATERIALS: A total of 1,036 urine samples were collected from 803 patients undergoing surveillance for UC. Of these, 1,016 samples were directly assessed using cytology, NMP22 Bladderchek and NMP22 enzyme-linked immunosorbent assay (ELISA), and the clinically validated Cxbladder Monitor test. An exploratory analysis was also performed comparing data from 157 samples where UroVysion fluorescence in situ hybridization analysis was performed locally. RESULTS: The sensitivity of Cxbladder Monitor (0.91) significantly outperformed cytology (0.22), NMP22 ELISA (0.26), and NMP22 BladderChek (0.11). The negative predictive value of Cxbladder Monitor was also superior at 0.96 compared with cytology (0.87), NMP22 ELISA (0.87), and NMP22 BladderChek (0.86). All false-negative results (n = 14) observed using Cxbladder Monitor were also negative for cytology, NMP22 ELISA, and NMP22 BladderChek. In the more limited set, UroVysion fluorescence in situ hybridization also had inferior sensitivity (0.33) and negative predictive value (0.92). CONCLUSIONS: The Cxbladder Monitor test significantly outperforms current Food and Drug Administration-approved urine-based monitoring tests, as well as cytology, in a large representative population undergoing surveillance for recurrent UC. This supports using Cxbladder Monitor as a confirmatory negative adjunct to cystoscopy or to justify postponing cystoscopic investigations in patients with a low risk of recurrence.

Use of a 17-Gene Prognostic Assay in Contemporary Urologic Practice: Results of an Interim Analysis in an Observational Cohort.

OBJECTIVE: To study the impact of genomic testing in shared decision making for men with clinically low-risk prostate cancer (PCa). MATERIALS AND METHODS: Patients with clinically low-risk PCa were enrolled in a prospective, multi-institutional study of a validated 17-gene tissue-based reverse transcription polymerase chain reaction assay (Genomic Prostate Score [GPS]). In this paper we report on outcomes in the first 297 patients enrolled in the study with valid 17-gene assay results and decision-change data. The primary end points were shared decision on initial management and persistence on active surveillance (AS) at 1 year post diagnosis. AS utilization and persistence were compared with similar end points in a group of patients who did not have genomic testing (baseline cohort). Secondary end points included perceived utility of the assay and patient decisional conflict before and after testing. RESULTS: One-year results were available on 258 patients. Shift between initial recommendation and shared decision occurred in 23% of patients. Utilization of AS was higher in the GPS-tested cohort than in the untested baseline cohort (62% vs 40%). The proportion of men who selected and persisted on AS at 1 year was 55% and 34% in the GPS and baseline cohorts, respectively. Physicians reported that GPS was useful in 90% of cases. Mean decisional conflict scores declined in patients after GPS testing. CONCLUSION: Patients who received GPS testing were more likely to select and persist on AS for initial management compared with a matched baseline group. These data indicate that GPS help guide shared decisions in clinically low-risk PCa.

Efficacy of Testosterone Suppression with Sustained-Release Triptorelin in Advanced Prostate Cancer.

INTRODUCTION: Androgen deprivation therapy (ADT) is a mainstay of treatment against advanced prostate cancer (PC). As a treatment goal, suppression of plasma testosterone levels to <50 ng/dl has been established over decades. Evidence is growing though that suppression to even lower levels may add further clinical benefit. Therefore, we undertook a pooled retrospective analysis on the efficacy of 1-, 3-, and 6-month sustained-release (SR) formulations of the gonadotropin-releasing hormone (GnRH) agonist triptorelin to suppress serum testosterone concentrations beyond current standards. METHODS: Data of 920 male patients with PC enrolled in 9 prospective studies using testosterone serum concentrations as primary endpoint were pooled. Patients aged 42-96 years had to be eligible for ADT and to be either naïve to hormonal treatment or have undergone appropriate washout prior to enrolment. Patients were treated with triptorelin SR formulations for 2-12 months. Primary endpoints of this analysis were serum testosterone concentrations under treatment and success rates overall and per formulation, based on a testosterone target threshold of 20 ng/dl. RESULTS: After 1, 3, 6, 9, and 12 months of treatment, 79%, 92%, 93%, 90%, and 91% of patients reached testosterone levels <20 ng/dl, respectively. For the 1-, 3-, and 6-month formulations success rates ranged from 80-92%, from 83-93%, and from 65-97% with median (interquartile range) serum testosterone values of 2.9 (2.9-6.5), 5.0 (2.9-8.7), and 8.7 (5.8-14.1) ng/dl at study end, respectively. CONCLUSION: In the large majority of patients, triptorelin SR formulations suppressed serum testosterone concentrations to even <20 ng/dl. Testosterone should be routinely monitored in PC patients on ADT although further studies on the clinical benefit of very low testosterone levels and the target concentrations are still warranted.

Comparative efficacy of tadalafil once daily in men with erectile dysfunction who demonstrated previous partial responses to as-needed sildenafil, tadalafil, or vardenafil.

OBJECTIVE: Phosphodiesterase type-5 inhibitors (PDE5Is) are first-line therapies for erectile dysfunction (ED). Sildenafil (SIL) and vardenafil (VAR) are approved for as-needed (PRN) dosing; tadalafil (TAD) is approved for both PRN and once-a-day (OaD) dosing for ED. Recent evidence suggests that TAD-OaD may be effective as therapy in men with an incomplete response to PRN-PDE5I therapy. This study evaluated whether TAD-OaD provides similar efficacy in men with ED who had previously demonstrated a partial response to PRN-PDE5I therapy. RESEARCH DESIGN AND METHODS: In this randomized, double-blind, placebo-controlled trial, men with a ≥3 month ED history received SIL 100 mg, TAD 20 mg, or VAR 20 mg during a 4 week open-label lead-in period. Those with International Index of Erectile Function - Erectile Function (IIEF-EF) domain scores <26 following lead-in treatment completed a 4 week washout period, then randomized to TAD 2.5 mg up-titrated to 5 mg, TAD 5 mg, or placebo (PBO) OaD for 12 weeks. MAIN OUTCOME MEASURES obtained from patients treated with TAD-OaD were compared to PBO-treated patients. Additionally, results of treatment with TAD-OaD were compared to results obtained from 4 week PRN-PDE5I therapy to determine whether OaD and PRN regimens provided comparable efficacy. CLINICAL TRIAL REGISTRATION: NCT01130532. MAIN OUTCOME MEASURES: International Index of Erectile Function (IIEF) domain scores; Sexual Encounter Profile (SEP) questions 2-5. RESULTS: Endpoint data was obtained from 590 men (391 TAD; 199 PBO). RESULTS for all IIEF and SEP measures were significantly better for TAD-OaD (p < 0.001 for all) compared to PBO and were comparable to those observed during PRN-PDE5I treatment. TAD 2.5 mg and TAD 5 mg OaD therapy were safe and generally well tolerated. CONCLUSION: Tadalafil once daily is a viable alternative to as-needed PDE5I therapy in men with ED. Key limitations include the lack of a PRN PDE5I study group during the double-blind period, and that many more patients took tadalafil than sildenafil or vardenafil during the PRN period.

Efficacy and safety of oxybutynin topical gel 3% in patients with urgency and/or mixed urinary incontinence: a randomized, double-blind, placebo-controlled study.

AIMS: To assess the efficacy and safety of oxybutynin transdermal gel 3% (OTG3%), with propylene glycol for enhanced skin permeation, in patients with urinary incontinence (UI). METHODS: In this phase 3 study, 626 patients ≥18 years old with urgency and/or mixed UI symptoms and predominantly urgency UI for ≥3 months were randomized 1:1:1 to receive 12 weeks of OTG3% 84 mg, OTG3% 56 mg, or placebo gel applied once daily to abdomen, inner/upper thigh, or upper arm/shoulder. Primary efficacy endpoint was change from baseline to Week 12 in weekly UI episodes recorded in 3-day bladder diaries. Results were compared using analysis of covariance. Adverse events (AEs) were monitored. RESULTS: Efficacy was assessed in 601 (intent-to-treat) and safety in 626 patients. At 12 weeks, OTG3% 84 mg/day achieved significantly greater improvement versus placebo in weekly UI episodes (mean change from baseline: -20.4 vs. -18.1; P < 0.05(a)), daily urinary frequency (-2.6 vs. -1.9; P = 0.001(b)), and urinary void volume (32.7 vs. 9.8; P < 0.0001(b)). Dry mouth, the most common treatment-related AE, occurred more often with OTG3% 84 mg/day (26/214 [12.1%]) vs. placebo (10/202 [5.0%]) (P = 0.028); 4 OTG3% patients withdrew because of dry mouth. Application site erythema occurred more often with OTG3% 84 mg/day (8/214 [3.7%]) versus placebo (2/202 [1.0%]) (P = NS); 12 OTG patients withdrew because of skin irritation. No serious treatment-related AEs occurred. CONCLUSIONS: OTG3% 84 mg/day was well tolerated and effective in improving urge incontinence or mixed UI symptoms with a predominance of UI in adults with overactive bladder.

Impact of low testosterone on response to treatment with tadalafil 5 mg once daily for erectile dysfunction.

OBJECTIVE: To evaluate, posthoc, the relationship between serum total testosterone and response to therapy in a study of tadalafil once daily for erectile dysfunction (ED). METHODS: Men were aged ≥18 years, with ≥3-month history of ED and partial prior response to on-demand (PRN) phosphodiesterase type 5 inhibitor (PDE5I) therapy. A 4-week maximum-dose PRN PDE5I run-in was followed by a 4-week nondrug washout period, then randomization to tadalafil 2.5 mg titrated to 5 mg or tadalafil 5 mg (pooled for analyses) or placebo once daily for 12 weeks. Analyses compared endpoint efficacy results between low- (<300 ng/dL) vs normal-testosterone (≥300 ng/dL) level subgroups. RESULTS: Improvements for tadalafil vs placebo were significant for the International Index of Erectile Function (IIEF) Erectile Function domain, Intercourse Satisfaction domain, Overall Satisfaction domain, and Question 15 (confidence in the ability to get and keep an erection; all P<.001), and for the Sexual Encounter Profile Questions 1-5 (all P≤.011). Analysis of covariance modeling identified significant treatment-by-subgroup interactions for the IIEF-Overall Satisfaction domain and erection confidence question and Sexual Encounter Profile Question 3. Comparing between tadalafil-treated testosterone subgroups, the IIEF-Erectile Function domain scores improved significantly more in men with normal vs low testosterone (P=.022); no other significant differences were identified for either placebo or tadalafil. No significant differences in pre-existing conditions were observed between tadalafil and placebo within the normal- and low-testosterone subgroups. CONCLUSION: In men with partial response to a PRN PDE5I, tadalafil 5 mg once daily significantly improved ED and sexual function vs placebo irrespective of testosterone levels.

A return to normal erectile function with tadalafil once daily after an incomplete response to as-needed PDE5 inhibitor therapy.

INTRODUCTION: An optimal outcome of an erectile dysfunction (ED) treatment is to enable a return to normal erectile function (as defined by an International Index of Erectile Function-Erectile Function [IIEF-EF] domain score ≥ 26). As-needed (PRN) phosphodiesterase type 5 (PDE5) inhibitor treatment does not always result in a return-to-normal erectile function. AIM: The combined studies evaluated whether treatment with tadalafil once daily would allow men to return to normal erectile function who had less than normal IIEF-EF domain scores while using a maximum dose of a PRN PDE5 inhibitor treatment. METHODS: Men were ≥ 18 years of age, sexually active, reported a ≥ 3-month history of ED, and had been taking the maximum dose of sildenafil citrate, vardenafil, or tadalafil PRN. Randomization to once-daily therapy with tadalafil 2.5 mg to 5 mg (N = 207), tadalafil 5 mg (N = 207), or placebo (N = 209) for 12 weeks followed a 4-week maximum dose PRN PDE5 treatment and 4-week nondrug lead periods. Two identical double-blind, randomized, placebo-controlled studies were conducted; combined results are reported. MAIN OUTCOME MEASURE: The main outcome measure was the percentage of subjects with a return-to-normal erectile function (IIEF-EF domain score ≥ 26) when treated with tadalafil once daily compared with placebo. RESULTS: In subjects not achieving normal erectile function with the maximum dose of a PRN PDE5 inhibitor, a higher percentage of subjects treated with tadalafil had an IIEF-EF domain score ≥ 26 at end point (tadalafil 2.5- to 5-mg group [39%]; tadalafil 5-mg group [40%]) compared with the placebo group (12.1%; P < 0.001). Tadalafil was generally well tolerated and adverse events observed were consistent with previous reports of tadalafil once daily. CONCLUSIONS: Treatment with tadalafil once daily significantly improved erectile function in men with mild to mild-moderate impairments in erectile function following PRN PDE5 inhibitor treatment.

Efficacy and safety of tadalafil 5 mg once daily for lower urinary tract symptoms suggestive of benign prostatic hyperplasia: subgroup analyses of pooled data from 4 multinational, randomized, placebo-controlled clinical studies.

OBJECTIVE: To assess the efficacy and safety of tadalafil, a phosphodiesterase 5 (PDE5) inhibitor efficacious for erectile dysfunction and lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH), in population subgroups, using pooled data from 4 international, randomized, placebo-controlled studies in men with LUTS/BPH. METHODS: The safety database included 1500 men randomized to tadalafil 5 mg once daily or placebo for 12 weeks. Changes in total International Prostate Symptom Score (IPSS), IPSS-quality of life index, and BPH impact index were examined overall, and changes in IPSS or adverse events (AEs) were examined across subgroups of interest. Treatment-group differences were assessed using analysis of covariance. RESULTS: Results of pooled data confirmed that tadalafil (N = 752) resulted in significant improvements from baseline vs placebo (N = 746) in IPSS (mean difference -2.3; P <.001), and also in BPH impact index and IPSS-quality of life index (both P <.001). Subgroup analyses demonstrated that IPSS improvements were significant regardless of baseline LUTS severity (IPSS <20/≥20), age (≤65/>65 years), recent previous use of α-blockers or PDE5 inhibitors, total testosterone level (<300/≥300 ng/dL), or prostate-specific antigen predicted prostate volume (<40/≥40 mL). [corrected] Rates of treatment emergent AEs were comparable between subgroups of baseline age (≤65/>65 years), previous PDE5 inhibitor use, and the presence or absence of pre-existing diabetes, hypertension, or cardiovascular disease (including hypertension), but somewhat higher for recent previous α-blocker use. CONCLUSION: In these pooled data analyses, tadalafil 5 mg improved LUTS/BPH across subgroups of age, LUTS severity, testosterone levels, and prostate volume. Rates of AEs were similar across the subgroups assessed.

Validity of the decreased sexual desire screener for diagnosing hypoactive sexual desire disorder.

The decreased sexual desire screener is a brief diagnostic instrument for generalized acquired hypoactive sexual desire disorder in women. During the screening visit of 2 clinical trials, the authors assessed sensitivity of the decreased sexual desire screener in premenopausal women presenting with decreased sexual desire. The authors compared diagnoses of generalized acquired hypoactive sexual desire disorder made by clinicians who were not trained or specialized in the diagnosis of female sexual dysfunction using the decreased sexual desire screener with diagnoses made by expert clinicians after an extensive diagnostic interview. The sensitivity of the decreased sexual desire screener was 0.946 in a North American trial and 0.960 in a European trial.

Hemodynamic effects of once-daily tadalafil in men with signs and symptoms of benign prostatic hyperplasia on concomitant α1-adrenergic antagonist therapy: results of a multicenter randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To investigate the safety of daily coadministration of α-blockers with tadalafil 5 mg in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia. The standard-of-care medical therapy for moderate to severe symptoms of benign prostatic hyperplasia is α(1)-adrenergic antagonist (α-blocker) therapy. METHODS: Men aged ≥ 45 years receiving stable α-blocker therapy were evaluated for eligibility before a 2-week single-blind, placebo lead-in period. Subsequently, 318 men were randomized to tadalafil 5 mg or placebo once daily for 12 weeks. Enrollment was monitored to ensure inclusion of men ≥ 75 years old and men taking nonuroselective α-blockers. The primary objective was to compare the proportion of men reporting treatment-emergent dizziness between the 2 treatment groups. Orthostatic vital signs, general safety, and the International Prostate Symptom Score were also assessed. RESULTS: The proportion of patients who reported treatment-emergent dizziness was not significantly different between the 2 treatment groups (tadalafil 7.0%; placebo 5.7%; P = .403). No difference between treatment groups was observed with respect to patients meeting the criteria for a positive orthostatic test (30 per treatment group, P = 1.00). The incidence of discontinuations was low among both treatment groups. CONCLUSION: Recognizing the limitations of the present study, the changes in the hemodynamic signs and symptoms were similar for the tadalafil and placebo groups in men with benign prostatic hyperplasia receiving concomitant α-blocker therapy. However, consistent with the results of previous clinical pharmacology studies of healthy subjects, a trend was seen for increased hemodynamic signs and symptoms in men taking nonuroselective α-blockers, most notably those taking doxazosin.