Kevin Carlson

Efficacy of Botulinum Toxin A Injection for Neurogenic Detrusor Overactivity and Urinary Incontinence: A Randomized, Double-Blind Trial

PURPOSE We determined the efficacy of onabotulinumtoxinA for neurogenic detrusor overactivity secondary to spinal cord injury or multiple sclerosis. MATERIALS AND METHODS In a prospective, double-blind, multicenter study 57 patients 18 to 75 years old with neurogenic detrusor overactivity secondary to spinal cord injury or multiple sclerosis and urinary incontinence (defined as 1 or more occurrences daily) despite current antimuscarinic treatment were randomized to onabotulinumtoxinA 300 U (28) or placebo (29) via cystoscopic injection at 30 intradetrusor sites, sparing the trigone. Patients were offered open label onabotulinumtoxinA 300 U at week 36 and followed a further 6 months while 24 each in the treatment and placebo groups received open label therapy. The primary efficacy parameter was daily urinary incontinence frequency on 3-day voiding diary at week 6. Secondary parameters were changes in the International Consultation on Incontinence Questionnaire and the urinary incontinence quality of life scale at week 6. Diary and quality of life evaluations were also done after open label treatment. RESULTS The mean daily frequency of urinary incontinence episodes was significantly lower for onabotulinumtoxinA than for placebo at week 6 (1.31 vs 4.76, p <0.0001), and for weeks 24 and 36. Improved urodynamic and quality of life parameters for treatment vs placebo were evident at week 6 and persisted to weeks 24 to 36. The most common adverse event in each group was urinary tract infection. CONCLUSIONS In adults with antimuscarinic refractory neurogenic detrusor overactivity and multiple sclerosis onabotulinumtoxinA is well tolerated and provides clinically beneficial improvement for up to 9 months.

Transobturator tape compared with tension-free vaginal tape for stress incontinence: a randomized controlled trial.

OBJECTIVE: To compare the effectiveness of transobturator tape with tension-free vaginal tape (TVT) in terms of objective cure of stress urinary incontinence (SUI) at 12 months postoperatively. METHOD: Women with SUI were randomly allocated to either transobturator tape or TVT procedures and reviewed at 12 months after surgery. The primary outcome was objective evidence of “cure,” evaluated by standardized pad test (cure defined as less than 1 g urine leaked). Other outcomes included complications, subjective cure, incontinence-related quality of life, return to usual sexual activity, and satisfaction with surgery. Primary analysis compared the proportion of patients in each group who were cured at 12-month follow-up. RESULTS: A total of 199 women participated (94 in the transobturator tape group, 105 in the TVT group). Sixty-eight women (81%) in the transobturator tape group were cured, compared with 67 (77%) in the TVT group (relative risk 1.05, 95% confidence interval 0.90–1.23, P=.577). On vaginal examination, the tape was palpable for 68 women (80%) in the transobturator tape group and for 24 (27%) in the TVT group (relative risk 0.22, 95% confidence interval 0.13–0.37, P<.001). More women in the transobturator tape group experienced groin pain during vaginal palpation (13 [15%] in the transobturator tape group and five [6%] in the TVT group, P=.044). Quality of life improved significantly from baseline in both groups (30-point improvement in IIQ-7 score for both groups). CONCLUSION: At 12 months, the majority of women had minimal leakage and their quality of life had improved significantly, but differences were not observed between groups. The presence of palpable tape, particularly among the transobturator tape group, is concerning; longer follow-up is needed to determine whether this outcome leads to extrusion or resolves over time. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00234754. LEVEL OF EVIDENCE: I

2012 Update: Guidelines for Adult Urinary Incontinence Collaborative Consensus Document for the Canadian Urological Association

Adult urinary incontinence (UI) is a highly prevalentcondition, and one which can have a major impacton patients’ quality of life. It is also a major focus ofa urologist’s workload. As a result, the Canadian UrologicalAssociation (CUA), with the aid of its Guidelines Committee,commissioned the development of a practice guideline documentin 2005 first authored by Dr. Jacques Corcos. As perthe CUA Guidelines Committee’s mandate, all guidelinesare subject to revision after 5 years.

Tolerability of 5 mg Solifenacin Once Daily Versus 5 mg Oxybutynin Immediate Release 3 Times Daily: Results of the VECTOR Trial

PURPOSE Although antimuscarinic treatment is indicated for overactive bladder, many patients discontinue it because of dry mouth. Of available antimuscarinics oxybutynin is associated with the highest dry mouth rate. We compared the safety and tolerability of 5 mg solifenacin vs 15 mg oxybutynin immediate release. MATERIALS AND METHODS At 12 Canadian centers a total of 132 patients with overactive bladder symptoms (greater than 1 urgency episode per 24 hours, and 8 or greater micturitions per 24 hours) were randomized to 5 mg solifenacin once daily or 5 mg oxybutynin 3 times daily for 8 weeks. The primary end point was the incidence and severity of dry mouth reported after direct questioning. Efficacy end points (3-day diary documented changes in urgency, frequency, incontinence, nocturia and voided volume), and changes on the Patient Perception of Bladder Condition scale and the Overactive Bladder Questionnaire were evaluated secondarily. RESULTS Of patients on solifenacin vs oxybutynin immediate release 35% vs 83% reported dry mouth (p <0.0001). Of patients reporting dry mouth severity was graded moderate by 13% and 42% of those on solifenacin and oxybutynin immediate release, and severe by 13% and 28%, respectively (p = 0.001). Patients in each group showed improvements in efficacy end points, and Patient Perception of Bladder Condition scale and Overactive Bladder Questionnaire scores from baseline to treatment end. CONCLUSIONS Significantly fewer patients on 5 mg solifenacin once daily reported dry mouth vs those receiving 5 mg oxybutynin immediate release 3 times daily. Significantly fewer patients on solifenacin reported moderate/severe dry mouth. Significantly fewer patients on solifenacin withdrew from study due to dry mouth and there were significantly fewer overall adverse events. Solifenacin and oxybutynin immediate release were efficacious in decreasing efficacy end points, and improved Patient Perception of Bladder Condition scale and Overactive Bladder Questionnaire results from baseline to treatment end.

Tolerability of solifenacin and oxybutynin immediate release in older (>65 years) and younger (≤65 years) patients with overactive bladder: sub-analysis from a Canadian, randomized, double-blind study

Abstract Objective: Overactive bladder (OAB) is a common condition whose prevalence increases with age. Antimuscarinic agents are the pharmacologic treatment of choice, but adverse events such as dry mouth may lead to early discontinuation. The purpose of this analysis was to compare the incidence and severity of dry mouth and other adverse events with solifenacin 5 mg/day and oxybutynin immediate release (IR) 15 mg/day in patients ≤65 years and >65 years in the Canadian VECTOR study (VEsicare in Comparison To Oxybutynin for oveRactive bladder patients). Research design and methods: VECTOR was a randomized, multicentre, prospective, double-blind, double-dummy study in 132 subjects with ≥1 urgency episode per 24 h, with or without urgency incontinence, and ≥8 micturitions per 24 h for ≥3 months. After a 2-week washout, patients received solifenacin 5 mg once daily or oxybutynin IR 5 mg tid for 8 weeks. For the current post-hoc analysis, adverse events were evaluated in subgroups of patients ≤65 years and >65 years, using a full logistic regression model, multinomial logit regression model and reduced model. Clinical trial registration: NCT00431041. Results: The incidence and severity of dry mouth and other adverse events with solifenacin were similar between younger and older patients. In both age subgroups, solifenacin 5 mg/day was associated with fewer episodes and lower severity of dry mouth, and a lower discontinuation rate, compared with oxybutynin IR 15 mg/day. Conclusions: Solifenacin 5 mg/day was better tolerated than oxybutynin IR 15 mg/day in younger (≤65 years) and older (>65 years) subgroups. Solifenacin was equally well tolerated in both age subgroups. Limitations of the analysis were that the study was not preplanned to perform post-hoc subgroup analysis, patients knew that dry mouth was a primary outcome, and the study used fixed doses of each drug.

Best practices for the treatment and prevention of urinary tract infection in the spinal cord injured population

The purpose of this review of clinical guidelines and best practices literature is to suggest prevention options and a treatment approach for intermittent catheter users that will minimize urinary tract infections (UTI). Recommendations are based both on evidence in the literature and an understanding of what is currently attainable within the Alberta context. This is done through collaboration between both major tertiary care centres (Edmonton and Calgary) and between various professionals who regularly encounter these patients, including nurses, physiatrists and urologists.

Assessment of antibiotic prophylaxis prescribing patterns for TURP: A need for Canadian guidelines?

BACKGROUND While antibiotic prophylaxis is recommended to all patients undergoing transurethral resection of prostate (TURP), little data exist regarding prescribing patterns of urologists prior to this procedure. Here, we sought to determine real-world antibiotic prophylaxis prescribing patterns at a high volume Canadian institution and determine compliance rates to recommendations put forth by the American Urological Associations (AUA) Best Practice Statement (BPS) on antimicrobial prophylaxis. METHODS A retrospective chart review of 488 patients undergoing TURP was conducted. Electronic medical records were reviewed to determine antibiotics prescribed 3 hours preoperatively and 24 hours postoperatively. For patients without a catheter, compliance was defined as those receiving an antibiotic prior to TURP. In patients with an indwelling catheter, compliance was defined as those receiving antibiotics from two different classes prior to surgery. RESULTS Overall, a total of 30 antibiotic regimens were utilized. The most common single antibiotic regimens prescribed were ciprofloxacin (32%), cefazolin (25%) and gentamicin (3%). In those patients with indwelling Foley catheters prior to TURP, a significant increase in gentamicin, as well as combination antibiotic regimens, was noted. The compliance rate with the AUA BPS in patients without a preoperative catheter was 81%, while the compliance rate for patients with an indwelling catheter prior to TURP was 37%. INTERPRETATION Collectively, our results demonstrate that prescribing patterns vary significantly prior to TURP, with compliance to AUA BPS being lower than anticipated. Overall, these results support educational efforts in this area, and the development of Canadian recommendations to improve uptake by practicing urologists.

Periurethral bulking agents for female stress urinary incontinence in Canada

Urethral bulking aims to improve urethral mucosal coaptation, and thus outlet resistance, in an effort to limit stress-induced leakage. While efforts have been made to employ bulking agents to treat stress urinary incontinence (SUI) for more than 100 years, we remain wanting for the perfect injectable. Regardless of the agent studied, efficacy is modest at best, repeat injections are the norm, and long-term followup is conspicuously lacking. This treatment, however, fills an important need in our armamentarium against SUI, serving those patients who are not candidates for more invasive interventions and those with multiple prior failed surgeries. This review offers a contemporary discussion on the role of periurethral bulking therapy in Canada, along with practical aspects of its application.

Management of patients with stress urinary incontinence after failed midurethral sling

Surgical failure rates after midurethral sling (MUS) procedures are variable and range from approximately 8-57% at five years of followup. The disparity in long-term failure rates is explained by a lack of long-term followup and lack of a clear definition of what constitutes failure. A recent Cochrane review illustrates that no high-quality data exists to recommend or refute any of the different management strategies for recurrent or persistent stress urinary incontinence (SUI) after failed MUS surgery. Clinical evaluation requires a complete history, physical examination, and establishment of patient goals. Conservative treatment measures include pelvic floor physiotherapy, incontinence pessary dish, commercially available devices (Uresta®, Impressa®), or medical therapy. Minimally invasive therapies include periurethral bulking agents (bladder neck injections) and sling plication. Surgical options include repeat MUS with or without mesh removal, salvage autologous fascial sling or Burch colposuspension, or salvage artificial urinary sphincter insertion. In this paper, we present the available evidence to support each of these approaches and include the management strategy used by our review panel for patients that present with SUI after failed midurethral sling.

Standardized follow-up program may reduce emergency room and urgent care visits for patients undergoing radical prostatectomy

INTRODUCTION The objective of the current study was to determine the impact of a standardized follow-up program on the morbidity and rates of hospital visits following radical prostatectomy (RP) in a tertiary, non-teaching urologic centre. METHODS Patients who underwent a RP in 2008 were retrospectively evaluated in this study. Postoperative morbidity for the entire cohort was assessed using the Modified Clavien Scale (MCS). Those patients readmitted to hospital or who visited an urban or rural emergency department (ED) within 90 days of surgery were further evaluated to determine the reason for readmission. RESULTS At our centre, 321 patients underwent RP in 2008 by 11 surgeons. Of the 321 patients, 77 (24.0%) visited an ED within 90 days, and 14 were readmitted to hospital, with an additional patient readmitted directly (with a total 15 readmissions, 4.7% overall). No patients died within the study period. In 2009 we launched a pilot study wherein 115 RP patients received scheduled and on-demand follow-up care by a dedicated nurse between May and November. We found that 90-day readmission rates among this cohort dropped to 5% and 2.6% for ED visits and hospital readmission, respectively. CONCLUSIONS At our tertiary non-teaching centre, a significant number of patients presented back to hospital within 90 days following RP. Most of these patients (80.8%) were managed entirely through an outpatient ED, and many visits were for routine postoperative care. Only 18.2% (4.7% of the 321 prostatectomy patients) were readmitted to hospital. These data point to a need for enhanced postoperative support of patients to reduce costly and often unnecessary visits to acute care EDs. This conclusion is supported by our early experience. Limitations include retrospective design, and variability in practice of surgeons in this study.