Jack Barkin

Levofloxacin for chronic prostatitis/chronic pelvic pain syndrome in men: a randomized placebo-controlled multicenter trial.

OBJECTIVESnTo perform a Canadian multicenter randomized placebo-controlled trial to evaluate the safety and efficacy of 6 weeks of levofloxacin therapy compared with placebo in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Uncontrolled studies have supported the use of antibiotics in CP/CPPS.nnnMETHODSnMen with a National Institutes of Health (NIH) diagnosis of CP/CPPS (specifically, no infection localized to the prostate) were randomized to levofloxacin (500 mg/day) or placebo for 6 weeks in 11 Canadian centers. Patients were assessed at baseline and at 3, 6, and 12 weeks with the NIH Chronic Prostatitis Symptom Index (NIH-CPSI) and global patient assessments (subjective global assessment and patient assessment questionnaire).nnnRESULTSnEighty men (average age 56.0 years, range 36 to 78; duration of symptoms 6.5 years, range 0.6 to 32) were randomized to receive levofloxacin (n = 45) or placebo (n = 35). All were evaluated in an intent-to-treat analysis. Both groups experienced progressive improvement in symptoms as measured by the NIH-CPSI. However, the difference in response was not statistically or clinically significant at end of treatment (6 weeks) or at the end of the follow-up visits (12 weeks). No patients withdrew because of adverse events. One patient withdrew before the 6-week assessment. Adverse events (all mild) were reported in 20% of the levofloxacin group and 17% of the placebo group.nnnCONCLUSIONSnThis pilot placebo-controlled study showed that 6 weeks of levofloxacin therapy in men diagnosed with CP/CPPS resulted in symptom improvement that was not significantly different from that with placebo at end of treatment or follow-up. The clinical ramifications of these findings need to be addressed.

Effect of pentosan polysulfate therapy on intravesical potassium sensitivity

OBJECTIVESnTo evaluate further the intravesical potassium sensitivity test (PST) as an indicator of the epithelial leak of interstitial cystitis (IC) and determine whether successful pentosan polysulfate (PPS; Elmiron) treatment is associated with a change in PST results. Most individuals with IC appear to have an abnormally permeable epithelium that allows urinary solutes such as potassium to penetrate to the bladder interstitium, provoking symptoms.nnnMETHODSnData were from an optimal dose trial of PPS in IC. Patients underwent a PST before and after a 32-week trial of 300, 600, or 900 mg PPS/day. The response to PPS treatment was measured using the Patient Overall Rating of Improvement in Symptoms scale. The before and after treatment PSTs and Patient Overall Rating of Improvement of Symptoms scores were compared.nnnRESULTSnOf 377 patients with IC at 28 centers, 302 (80%) had a positive PST at entry. Of the 198 patients who completed the study, 153 were PST positive at entry and 92 (60%) showed clinical improvement at exit. Clinically improved patients had significant improvement on the PST analog pain and urgency scales (3.2 to 1.3 and 3.6 to 1.9, respectively; P <0.0001). In contrast, patients with no clinical improvement had no significant change in pain (3.1 to 2.7) or urgency (3.6 to 3.2).nnnCONCLUSIONSnPST shows abnormal epithelial permeability in most patients with IC and a significant reduction in this permeability after successful PPS therapy. PST appears to be a valid indicator of epithelial abnormality and a reliable test in the diagnosis of IC.

Pentosan polysulfate therapy for chronic nonbacterial prostatitis (chronic pelvic pain syndrome category IIIA) : A prospective multicenter clinical trial

OBJECTIVESnChronic nonbacterial prostatitis/chronic pelvic pain syndrome (CPPS) has clinical and perhaps etiologic characteristics similar to interstitial cystitis. Pentosan polysulfate sodium (PPS), an oral medication indicated for the treatment of interstitial cystitis, has shown moderate benefit in reducing chronic pelvic pain and voiding symptoms in patients with interstitial cystitis. We undertook a prospective open-label, multicenter Phase II pilot study to examine the potential efficacy of PPS in the treatment of CPPS in men, using outcome tools validated for CPPS in men.nnnMETHODSnPatients with a diagnosis consistent with National Institutes of Health (NIH) CPPS category IIIA (inflammatory) were treated with PPS, 100 mg three times daily, for 6 months. The evaluation at baseline, 3 months, and 6 months consisted of the Symptom Severity Index, a Symptom Frequency Questionnaire, the NIH-Chronic Prostatitis Symptom Pain Index (NIH-CPSI), a quality-of-life assessment, and a subjective global assessment.nnnRESULTSnThirty-two patients (mean age 45.5 +/- 11 years; duration of symptoms 9.2 +/- 12 years) were enrolled in five centers; 28 patients were available for evaluation. Seven patients experienced drug-related side effects, including hair loss (n = 2), headache (n = 2), mild nausea (n = 1), mild weight gain (n = 1), and skin flushing (n = 1). The decrease in frequency (Symptom Frequency Questionnaire 28.1 to 17.9), severity (Symptom Severity Index 53.6 to 36.3), and combined location/frequency/severity of pain (NIH-CPSI pain 14.5 to 9.2) symptom scores at 6 months compared with baseline was significant. The decrease was associated with a significant improvement in patients quality of life (quality-of-life assessment 5.3 to 3.8). Forty-three percent of the patients had a greater than 50% improvement in the Symptom Frequency Questionnaire, Symptom Severity Index, and NIH-CPSI (rated as clinically significant improvement). At 6 months, mild, moderate, and marked improvement was noted (subjective global assessment) by 33%, 19%, and 15% of the patients, respectively.nnnCONCLUSIONSnPPS is well tolerated and appears to have efficacy in reducing the severity and frequency of general symptoms, reducing specific pain symptoms, and improving the quality of life in many male patients with CPPS. The results of this study justify the initiation of a randomized controlled trial comparing the safety and efficacy of PPS to placebo.

The Canadian Enuresis Study and Evaluation--short- and long-term safety and efficacy of an oral desmopressin preparation.

Objective: To evaluate the long-term (12 months) efficacy and safety of oral desmopressin (DDAVP). Material and Methods: A total of 256 healthy children (6-18 years old) with nocturnal enuresis with a frequency of S 10 wet nights during a 4-week observation period were eligible for inclusion in the study. Initially 0.2 r mg of DDAVP was given for 14 nights. Those achieving a >90% reduction in the number of wet nights over the observation period (full responders) began a 12-week continuous treatment period at this dose. The remaining children received 0.4 r mg for an additional 14 nights. Those achieving a S 50% reduction in the number of wet nights (responders) commenced a 12-week continuous treatment period at this dose. Children with a <50% reduction in the number of wet nights at this point were withdrawn from the study. Each 12-week treatment period was followed by a treatment-free period of 7-28 days. Children who remained dry during that period were assigned a full response and terminated the trial. Children with S 2 wet nights during that period immediately began a new 12-week treatment period at the previous dose. This was repeated for 12 months and thereafter the medication dose was tapered by halving over a 4-week period. Results: A total of 117/236 children who completed the titration period (49.6%; 95% confidence interval 40-57%) responded (>50% reduction over baseline). Throughout the study their response rate remained constant at , 74%. Continuous treatment reduced the median number of wet nights during the observation period from 5.75 to 1.00 per week. A total of 12.4% of children received the 0.2 r mg dose and 87.6% the 0.4 r mg dose. The proportion of full responses increased over the course of the study from 5.8% to 37.5%. DDAVP was well tolerated: the majority of reported adverse events were mild, although two adverse events leading to withdrawal were reported. Conclusions: Oral DDAVP provides an effective and well-tolerated means of providing long-term control in children with nocturnal enuresis. Long-term treatment increases the response rate.

Two Year Durability after Crossover to the Prostatic Urethral Lift from Randomized, Blinded Sham

To evaluate the 24‐month effectiveness of the prostatic urethral lift (PUL) procedure in men with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) assessed through a crossover study.

High Intensity Focused Ultrasound for Radiorecurrent Prostate Cancer: A North American Clinical Trial

Purpose We determined the safety and efficacy of whole gland high intensity focused ultrasound in men with radiorecurrent prostate cancer. Materials and Methods A total of 100 men with clinically localized recurrent prostate cancer at least 2 years after external beam radiation therapy underwent whole gland high intensity focused ultrasound in an open label trial from 2009 to 2012. Treatments were performed at 16 sites, including 14 in the United States and 2 in Canada. The primary end point was the combination of a prostate specific antigen nadir of 0.5 ng/ml or less and negative biopsy at 12 months. Validated questionnaires were administered to monitor changes in urinary and sexual function. Results Of the 100 treated men, in whom mean age was 70 years (range 53 to 83), 78 completed the 12‐month biopsy, which was negative in 63 (81%). Mean prostate specific antigen was 4.9 ng/ml (range 0.4 to 14) and the median Gleason score was 7. The 1‐year end point of a prostate specific antigen nadir of 0.5 ng/ml or less plus negative biopsy was achieved in 50 men. During post‐trial followup mean prostate specific antigen at 2 years was 1.1 ng/ml (range 0.1 to 17) in 33 patients. Adverse events developed in 91 men through 12 months, which were CTCAE grade 1 in 67, grade 2 in 80 and grade 3 in 20. Treatment related grade 3 adverse events included rectal fistulas in 5 men, which required surgery in 3, osteitis pubis in 3 and hematuria requiring intervention in 3. Treatment related grade 3 adverse events developed early in the trial and appeared related to operator experience. There were no life threatening adverse events or treatment related deaths. Conclusions Whole gland high intensity focused ultrasound appears reasonably safe and effective to treat radiorecurrent prostate cancer. The rate of complications, which are potentially severe, was acceptable, especially considering the advanced, refractory nature of the disease and the limited treatment options.

Mirabegron as Add-on Treatment to Solifenacin in Incontinent Overactive Bladder Patients with an Inadequate Response to Solifenacin Monotherapy: Responder Analyses and Patient-Reported Outcomes from the BESIDE study

PURPOSEnWe investigated improvements in overactive bladder and patient reported outcomes in patients with overactive bladder and refractory incontinence treated with mirabegron 50 mg plus solifenacin 5 mg vs solifenacin 5 or 10xa0mg.nnnMATERIALS AND METHODSnPatients with overactive bladder who were incontinent despite 4 weeks of single-blind daily solifenacin 5 mg were randomized 1:1:1 to a double-blind daily combination of mirabegron 50 mg/solifenacin 5 mg, or solifenacin 5 or 10 mg for 12 weeks. The mirabegron dose was increased from 25 to 50 mg after week 4. Symptom bother, health related quality of life and patient perception of bladder condition were assessed by OAB-q (Overactive Bladder Questionnaire) and the PPBC (Patient Perception of Bladder Condition) questionnaire, respectively. Responder rates were based on a 50% reduction in daily incontinence, zero incontinence episodes and fewer than 8xa0micturitions per 24xa0hours with minimal important differences in OAB-q and PPBC.nnnRESULTSnOverall 2,174 patients with a median age of 59 years were randomized, including 727 to the combination, 728 to solifenacin 5 mg and 719 to solifenacin 10 mg. Symptom bother, total health related quality of life and its subscales (coping, concern and social), and PPBC were significantly improved with combination vs solifenacin monotherapy (p <0.05). The odds of achieving clinically meaningful improvements in incontinence, micturition frequency, symptom bother, health related quality of life and PPBC were significantly higher for combination than solifenacin monotherapy. The odds of becoming continent was 47% and 28% higher for combination vs solifenacin 5 andxa010 mg (OR 1.47, 95% CI 1.17-1.84, pxa0= 0.001 and OR 1.28; 95% CI 1.02-1.61, p = 0.033, respectively).nnnCONCLUSIONSnSignificantly more patients on the combination achieved clinically meaningful improvements inxa0incontinence and micturition frequency. Improvements were accompanied by similar improvements in PPBC, symptom bother and health related quality of life.

Canadian Urological Association guideline on male lower urinary tract symptoms/benign prostatic hyperplasia (MLUTS/BPH): 2018 update

MLUTS secondary to BPH remains one of the most common age-related disorders afflicting men. As the aging of the Canadian population continues, more men will be seeking advice and looking for guidance from their healthcare providers on the management of their symptoms. The information offered in this guideline document, based on consensus evaluation of the best available evidence, will aid Canadian urologists as they strive to provide state-of-the-art care to their patients.

Mirabegron as Add-on Treatment to Solifenacin in Incontinent Overactive Bladder Patients with an Inadequate Response to Solifenacin Monotherapy

PURPOSEnWe investigated improvements in overactive bladder and patient reported outcomes in patients with overactive bladder and refractory incontinence treated with mirabegron 50 mg plus solifenacin 5 mg vs solifenacin 5 or 10xa0mg.nnnMATERIALS AND METHODSnPatients with overactive bladder who were incontinent despite 4 weeks of single-blind daily solifenacin 5 mg were randomized 1:1:1 to a double-blind daily combination of mirabegron 50 mg/solifenacin 5 mg, or solifenacin 5 or 10 mg for 12 weeks. The mirabegron dose was increased from 25 to 50 mg after week 4. Symptom bother, health related quality of life and patient perception of bladder condition were assessed by OAB-q (Overactive Bladder Questionnaire) and the PPBC (Patient Perception of Bladder Condition) questionnaire, respectively. Responder rates were based on a 50% reduction in daily incontinence, zero incontinence episodes and fewer than 8xa0micturitions per 24xa0hours with minimal important differences in OAB-q and PPBC.nnnRESULTSnOverall 2,174 patients with a median age of 59 years were randomized, including 727 to the combination, 728 to solifenacin 5 mg and 719 to solifenacin 10 mg. Symptom bother, total health related quality of life and its subscales (coping, concern and social), and PPBC were significantly improved with combination vs solifenacin monotherapy (p <0.05). The odds of achieving clinically meaningful improvements in incontinence, micturition frequency, symptom bother, health related quality of life and PPBC were significantly higher for combination than solifenacin monotherapy. The odds of becoming continent was 47% and 28% higher for combination vs solifenacin 5 andxa010 mg (OR 1.47, 95% CI 1.17-1.84, pxa0= 0.001 and OR 1.28; 95% CI 1.02-1.61, p = 0.033, respectively).nnnCONCLUSIONSnSignificantly more patients on the combination achieved clinically meaningful improvements inxa0incontinence and micturition frequency. Improvements were accompanied by similar improvements in PPBC, symptom bother and health related quality of life.

Adult UrologyVoiding DysfunctionMirabegron as Add-On Treatment to Solifenacin in Patients with Incontinent Overactive Bladder and an Inadequate Response to Solifenacin Monotherapy

PURPOSEnWe investigated improvements in overactive bladder and patient reported outcomes in patients with overactive bladder and refractory incontinence treated with mirabegron 50 mg plus solifenacin 5 mg vs solifenacin 5 or 10xa0mg.nnnMATERIALS AND METHODSnPatients with overactive bladder who were incontinent despite 4 weeks of single-blind daily solifenacin 5 mg were randomized 1:1:1 to a double-blind daily combination of mirabegron 50 mg/solifenacin 5 mg, or solifenacin 5 or 10 mg for 12 weeks. The mirabegron dose was increased from 25 to 50 mg after week 4. Symptom bother, health related quality of life and patient perception of bladder condition were assessed by OAB-q (Overactive Bladder Questionnaire) and the PPBC (Patient Perception of Bladder Condition) questionnaire, respectively. Responder rates were based on a 50% reduction in daily incontinence, zero incontinence episodes and fewer than 8xa0micturitions per 24xa0hours with minimal important differences in OAB-q and PPBC.nnnRESULTSnOverall 2,174 patients with a median age of 59 years were randomized, including 727 to the combination, 728 to solifenacin 5 mg and 719 to solifenacin 10 mg. Symptom bother, total health related quality of life and its subscales (coping, concern and social), and PPBC were significantly improved with combination vs solifenacin monotherapy (p <0.05). The odds of achieving clinically meaningful improvements in incontinence, micturition frequency, symptom bother, health related quality of life and PPBC were significantly higher for combination than solifenacin monotherapy. The odds of becoming continent was 47% and 28% higher for combination vs solifenacin 5 andxa010 mg (OR 1.47, 95% CI 1.17-1.84, pxa0= 0.001 and OR 1.28; 95% CI 1.02-1.61, p = 0.033, respectively).nnnCONCLUSIONSnSignificantly more patients on the combination achieved clinically meaningful improvements inxa0incontinence and micturition frequency. Improvements were accompanied by similar improvements in PPBC, symptom bother and health related quality of life.