Recruitment of participants to a clinical trial of botanical therapy for benign prostatic hyperplasia.

OBJECTIVES: The timely recruitment of study participants is a critical component of successful trials. Benign prostatic hyperplasia (BPH), a common nonmalignant urologic condition among older men, is characterized by lower urinary tract symptoms (LUTS). Successful recruitment methods for a trial of medical therapy for BPH, Medical Therapy of Prostate Symptoms (MTOPS), were mass mailing and advertising. The Complementary and Alternative Medicines Trial for Urological Symptoms (CAMUS) was designed to evaluate a botanical therapy, saw palmetto, for the treatment of BPH. The objective of this study was to evaluate recruitment strategies for CAMUS and to contrast the baseline characteristics of CAMUS participants with those recruited to a similar trial using conventional medical therapy. DESIGN: CAMUS is a randomized, double-blind, placebo-controlled trial designed to evaluate the effects of saw palmetto given at escalating doses over an 18-month period on relief from LUTS. SUBJECTS: The target enrollment goal was 350 men with LUTS from 11 clinical centers over a 12-month period. The recruitment techniques used and participants contacted, screened, and randomized through each technique were obtained from the clinical centers. Baseline characteristics of the CAMUS participants were compared with participants in the MTOPS trial who met the CAMUS eligibility criteria for LUTS. RESULTS: The target enrollment goal was achieved in 11 months. The overall monthly recruitment rate per site was 3.7 and ranged from 2.4 to 8.0. The most successful recruitment methods were mass mailing and advertising, which accounted for 39% and 35% of the study participants, respectively. In comparison to MTOPS participants, CAMUS participants were younger, more highly educated, more diverse, and had less severe urinary symptoms. CONCLUSIONS: Successful recruitment methods for CAMUS were similar to those in MTOPS. The use of botanical therapy attracted a less symptomatic and more educated study population.

A real-life multicentre clinical practice study to evaluate the efficacy and safety of intravesical chondroitin sulphate for the treatment of interstitial cystitis.

OBJECTIVE: To report a multicentre, community based open-label study designed to assess the efficacy and safety of intravesical sodium chondroitin sulphate in the treatment of patients with the clinical diagnosis of interstitial cystitis (IC). Chondroitin sulphate is a naturally occurring glycosaminoglycan (GAG) in the bladder mucus layer and changes in this GAG have been implicated in the pathogenesis of IC, and small single-centre studies have suggested that intravesical chondroitin sulphate may have efficacy in IC. PATIENTS AND METHODS: Patients with IC were treated with sodium chondroitin sulphate (Uracyst, Stellar Pharmaceuticals Inc., London ON, Canada) solution 2.0% via urinary catheter weekly for 6 weeks and then monthly for 16 weeks for a total of 10 treatments. The primary efficacy endpoint was the percentage of responders to treatment as indicated by a marked or moderate improvement on a seven-point patient Global Response Assessment (GRA) scale at week 10 (4 weeks after the initial six treatments) compared with baseline. A major secondary efficacy endpoint (durability) was the percentage of responders on the GRA scale after 10 treatments. Additional secondary efficacy objectives were differences from baseline in Patient Symptom/Problem Index scores over the course of the treatment compared with baseline. RESULTS: In all, 47% of the 53 enrolled patients with long standing moderately severe IC (mean [SD, range] diagnosis of IC 3.0 [3.4, 0.1-16] years; duration of symptoms 9.2 [9.2, 1-39] years; baseline symptom score 14.2 [3.2]) were responders at week 10. At 24 weeks, 60% were responders. There was a statistically and clinically significant decrease in the mean (SD) symptom and bother scores from baseline at 10 weeks and 24 weeks, at 9.0 (4.3) and 8.1 (5.0), respectively (P < 0.001). There were no significant safety issues during the study. CONCLUSIONS: This multicentre community based real-life clinical practice study suggests that intravesical chondroitin sulphate may have an important role in the treatment of IC and validates the rationale for a randomized placebo-controlled trial.

The Canadian Benign Prostatic Hyperplasia Audit Study (CanBas).

OBJECTIVE: To determine the prevalence, diagnostic patterns and management of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) in Canadian urology outpatient practice. METHODS: Representative urologists were randomly selected from lists provided by the Canadian and Quebec Urological Associations. Each patient identified with a BPH diagnosis during a typical 2-consecutive-week period during April, May or June 2007 was asked to complete a corresponding International Prostate Symptom Score (IPSS) questionnaire. Each day, the participant urologist completed an outpatient log and a detailed programmed chart review to transcribe demographics, investigations and treatments associated with each BPH patient. RESULTS: Eighty-six urologists were invited to participate. Thirty-eight (44.2%) agreed, and 27 of those (71.1%) submitted evaluable data for the audit. Of the 5616 patients seen in outpatient practice (average 208 per urologist), 4324 (77%) were male. A BPH diagnosis was identified in 19.6% of the men (n = 849; mean age 69.5, standard deviation [SD] 10, yr; age range 40-100 yr; mean duration of symptoms 4.8, SD 4.2, yr; mean IPSS score 12.3, SD 7.4; mean prostate specific antigen [PSA] 3.9, SD 3.9, ng/mL). Twenty-four percent of patients had prostates that were rated as large, 50% as medium and 26% as small. PSA level correlated positively with prostate volume. Twenty-two percent were initial consultations for LUTS and 78% were repeat visits. Diagnostic evaluation tended to follow those examinations and tests recommended by the Canadian BPH guidelines. Treatment choices tended to follow an evidence-based algorithm with respect to treatment choices for men in the various prostate-volume and PSA groups. CONCLUSION: This prospective audit indicates that BPH remains a common condition managed by urologists in outpatient practice. Investigations and treatments confirm that Canadian urologists appear to be following Canadian BPH guidelines as well as the most recent evidence from the literature.

Prevalence, diagnosis, characterization, and treatment of prostatitis, interstitial cystitis, and epididymitis in outpatient urological practice: the Canadian PIE Study.

OBJECTIVES: To determine the prevalence, diagnostic patterns, and management of prostatitis, interstitial cystitis, and epididymitis (PIE) in Canadian urology outpatient practice. METHODS: Representative urologists were randomly selected from the Canadian and Quebec Urological Associations. Each patient identified with a PIE diagnosis during a typical 2-consecutive-week period during April 2004 to July 2004 was requested to complete a corresponding Chronic Prostatitis Symptom Index (CPSI), O'Leary-Sant Symptom Index (OSSI), or a Chronic Epididymitis Symptom Index (CESI). Each day the participant urologist completed an outpatient log and a detailed programmed chart review to transcribe demographics, investigations, and treatments associated with each PIE patient. RESULTS: Sixty-five urologists were invited to participate. Fifty-seven (88%) agreed, and 48 (74%) completed the audit. Of the 8712 patients seen in outpatient practice (average 182 per urologist), 2675 were female and 6037 male. Prostatitis was identified in 2.7% of the men (n = 166; mean age 50 years; mean duration 3.1 years; mean CPSI score 19.7), interstitial cystitis in 2.8% of patients (n = 242; 211 women [7.9%], 26 men [0.4%]; mean age 50.2 years, mean duration 4.5 years, mean OSSI score 11.8), and epididymitis in 0.9% of men (n = 57; mean age 41.1 years, mean duration 2.5 years, mean CESI score 15.5). There was wide variance in investigations and treatments. CONCLUSIONS: This prospective audit indicates that prostatitis might not be as common as frequently believed and that interstitial cystitis is more common, and it represents the first estimate of the prevalence of epididymitis in urologic practice. The wide variance in investigations and treatments confirms the need for practice management guidelines.

Failure of a monotherapy strategy for difficult chronic prostatitis/chronic pelvic pain syndrome.

PURPOSE: We determined the effect of a best evidence based monotherapeutic strategy for patients diagnosed with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) referred to a specialized prostatitis clinic. MATERIALS AND METHODS: Patients with CP/CPPS referred by urologists after failure of prescribed therapy for evaluation and treatment at Queen's University prostatitis research clinic were extensively evaluated, aggressively treated following a standardized treatment algorithm and followed for 1 year using a validated prostatitis specific symptom and quality of life instrument, the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI). All patients underwent a standardized protocol for CP/CPPS including a history, physical examination, standard 4-glass test, plus urethral swab and semen for microscopy and culture, uroflowmetry and residual urine determination. Treatment followed a best evidence based strategy with a standardized monotherapy based algorithm. RESULTS: A total of 100 consecutive patients with CP/CPPS (average age 42.2 years, range 20 to 70 and average symptom duration 6.5 years, range 0.5 to 39) had 1-year followup after initial evaluation. Patients were prescribed treatment based on documentation of "failed," "successful" and "never tried" therapies based on a standardized treatment algorithm. Patients treated successfully were continued on the prescribed therapy, while therapy was discontinued and new therapy instituted (based on algorithm) in those in whom the initially prescribed therapy failed. At 1 year there was a statistically significant decrease in total NIH-CPSI (23.3 to 19.5, p = 0.0004), pain (11.0 to 9.4, p = 0.03) and quality of life (7.7 to 6.1, p <0.001), but not voiding (4.6 to 4.0, p = 0.12). A perceptible 25% decrease in total NIH-CPSI symptom score was noted in 37% and the greatest improvement was in the quality of life domain (43% of patients had greater than 25% improvement in quality of life). Of the patients 35% had a significant decrease of greater than 6 points in total NIH-CPSI. A clear, clinically significant improvement in total NIH-CPSI (greater than 50% decrease) was noted in 19%. CONCLUSIONS: Approximately a third of patients with treatment refractory CP/CPPS undergoing extensive evaluation and therapy based on a sequential monotherapy treatment strategy in a specialized prostatitis clinic had at least modest improvement in symptoms during 1 year. This study confirms that a treatment strategy based on the sequential application of monotherapies for patients with a long history of severe CP/CPPS remains relatively poor.

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

OBJECTIVES: To 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. METHODS: Men 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). RESULTS: Eighty 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. CONCLUSIONS: This 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.

Cytologic evaluation of urine is important in evaluation of chronic prostatitis.

OBJECTIVES: Cytologic examination of the urine has not been a recommended part of the diagnostic workup for patients presenting with chronic prostatitis. We identified 3 patients referred to our tertiary Prostatitis Research Clinic who had carcinoma in situ of the bladder discovered after evaluation of urine cytology. METHODS: One hundred fifty consecutive patients referred to the Queen's University Prostatitis Clinic during 2000 and 2001 underwent extensive evaluation, including collection of urine specimen for cytologic examination if they also had symptoms compatible with interstitial cystitis (urinary frequency, urgency, and suprapubic pain). RESULTS: Three patients, who were referred to our tertiary prostatitis clinic after being evaluated and treated by other urologists for an average of 3.5 years for chronic prostatitis, were eventually diagnosed with carcinoma in situ of the bladder. The patients were older than the average patient referred to our specialized clinic (average age 61 years compared with 42 years for the average patient). All 3 patients complained of pain (suprapubic and/or perineal) and irritative voiding symptoms, and 2 had dysuria. Only 1 of these patients had microscopic hematuria. CONCLUSIONS: We recommend that urine cytology become a diagnostic test for men presenting with prostatitis-like symptoms, particularly if the symptom complex includes irritative voiding symptoms, dysuria, and suprapubic/bladder pain.

The patient with chronic epididymitis: characterization of an enigmatic syndrome.

PURPOSE: We provide a baseline description of men diagnosed with chronic epididymitis, explore relevant associations that may be important etiological factors and suggest a classification system and specific symptom assessment tool. MATERIALS AND METHODS: Men diagnosed with chronic epididymitis, described as symptoms of discomfort or pain at least 3 months in duration in the scrotum, testicle or epididymis localized to 1 or each epididymis on clinical examination, completed an extensive specific clinical inventory questionnaire. Evaluation included demographics, preceding and concurrent clinical history, duration since diagnosis, associated and previous clinical associations, frequency and severity of prostatitis, voiding and sexual symptoms, specific and general quality of life, and history of investigation and/or treatment for the condition. Volunteers with no past or concurrent history of chronic epididymitis completed similar clinical inventory questionnaires. RESULTS: A total of 50 consecutive men 21 to 83 years old (average age 46) diagnosed with chronic epididymitis who had an average symptom duration of 4.9 years (range 0.25 to 29) were enrolled in the study. The average pain score plus or minus standard deviation was 4.7 +/- 2.1 (range 0 to 10). Of the men 16% were reasonably satisfied with their quality of life. Although 66% of the patients thought about the symptoms some or a lot, in only 30% did symptoms keep them from doing the kinds of things that they would usually do. The most common previous therapies recollected by the patients were antibiotics (74%) and anti-inflammatory agents (36%). At the time of the survey 26% of the men were on some type of pain medication. There were no significant epidemiological, sexual, medical or associated factors that differentiated patients with chronic epididymitis from the 20 controls. A chronic epididymitis classification system (inflammatory, obstructive and epididymalgia) and a symptom assessment index based on assessing pain and quality of life-impact was developed. CONCLUSIONS: This comprehensive clinical survey of men diagnosed with chronic epididymitis is the first step for defining and characterizing this particular population. Development of a classification system and symptom assessment index may direct further studies in the etiology, epidemiology and management of chronic epididymitis.