Sidney B. Radomski

Clinical efficacy and safety of tolterodine compared to oxybutynin and placebo in patients with overactive bladder.

Abstract: This study compared the clinical efficacy (determined from micturition diaries) and safety of 12 weeks’ treatment with either tolterodine 2 mg twice daily, oxybutynin 5 mg three times daily or placebo in patients with an overactive bladder. A total of 277 patients were randomized and treated at 25 centers. Both tolterodine and oxybutynin significantly increased volume voided/micturition compared to placebo. Both treatment groups evoked greater decreases in micturitions per 24 hours and incontinence episodes per 24 hours compared to placebo; however, only tolterodine was significantly better than placebo in reducing micturition frequency. Tolterodine and oxybutynin were equivalent in their effectiveness. Tolterodine was significantly better tolerated than oxybutynin when adverse events (particularly frequency and intensity of dry mouth), dose reduction and patient withdrawals were considered. Oxybutynin is an effective drug whose frequent adverse effects limit its clinical usefulness. Tolterodine has equivalent efficacy to oxybutynin, but with less severe adverse effects. This will allow patients to receive more effective treatment for their condition, with better compliance.

OnabotulinumtoxinA for the Treatment of Patients with Overactive Bladder and Urinary Incontinence: Results of a Phase 3, Randomized, Placebo Controlled Trial

Purpose: Overactive bladder affects 12% to 17% of the general population and almost a third experience urinary incontinence, which may severely impact health related quality of life. Oral anticholinergics are the mainstay of pharmacological treatment but they are limited by inadequate efficacy or side effects, leading to a high discontinuation rate. We report the results of the first large (557 patients), phase 3, placebo controlled trial of onabotulinumtoxinA in patients with overactive bladder and urinary incontinence inadequately managed with anticholinergics. Materials and Methods: Eligible patients with overactive bladder, 3 or more urgency urinary incontinence episodes in 3 days and 8 or more micturitions per day were randomized 1:1 to receive intradetrusor injection of onabotulinumtoxinA 100 U or placebo. Co‐primary end points were the change from baseline in the number of urinary incontinence episodes per day and the proportion of patients with a positive response on the treatment benefit scale at posttreatment week 12. Secondary end points included other overactive bladder symptoms and health related quality of life. Adverse events were assessed. Results: OnabotulinumtoxinA significantly decreased the daily frequency of urinary incontinence episodes vs placebo (−2.65 vs −0.87, p <0.001) and 22.9% vs 6.5% of patients became completely continent. A larger proportion of onabotulinumtoxinA than placebo treated patients reported a positive response on the treatment benefit scale (60.8% vs 29.2%, p <0.001). All other overactive bladder symptoms improved vs placebo (p ≤0.05). OnabotulinumtoxinA improved patient health related quality of life across multiple measures (p <0.001). Uncomplicated urinary tract infection was the most common adverse event. A 5.4% rate of urinary retention was observed. Conclusions: OnabotulinumtoxinA 100 U showed significant, clinically relevant improvement in all overactive bladder symptoms and health related quality of life in patients inadequately treated with anticholinergics and was well tolerated.

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.

Evaluation and Treatment of Blunt Renal Trauma

We examined retrospectively the records of 126 patients with blunt renal trauma to determine the criteria for radiological investigations and the imaging study of choice. Of the 3,993 patients admitted to our regional trauma unit during the last 13 years 126 (3.1%) had blunt renal trauma. Mean patient age was 32 years (range 13 to 87 years) and the male-to-female ratio was 3:1. Mean followup was 7 months (median 4 months). Of the patients 72% had a minor renal injury, 17% had a moderate injury and 11% had a major renal injury. Treatment was conservative in 114 patients, while 9 underwent a genitourinary operation. Results were excellent in 87% of the patients and good in 8%, while 5% failed treatment. All patients who had microscopic hematuria without shock had minor injuries. Excretory urograms (IVPs) were normal in 74% and 39% of the patients when performed for minor and moderate renal injuries, respectively. Computerized tomography (CT) was abnormal in all cases when performed, and was more sensitive and specific than an IVP. Therefore, the majority of patients with blunt renal trauma can be treated conservatively with an excellent result. Furthermore, radiological investigations are not needed in those with microscopic hematuria and no shock. When radiological investigations are indicated a CT scan is the imaging study of choice.

Risk Factors Associated with Penile Prosthesi Infection

AbstractWe reviewed all 269 patients who underwent penile prosthetic implantation during the last 10 years. The data were analyzed to determine the rate of penile prosthesis infection and to determine the risk factors associated with these infections in this group. We also examined the effect of strict surgical technique, intraoperative scrub and perioperative antibiotics on these implant infections. All patients had perioperative antibiotics, an intraoperative shave and a 15-minute intraoperative skin preparation. There were 162 semirigid and 107 inflatable prostheses inserted. Mean followup was 32 months (range 2 to 123 months). Only 6 patients had an infection, with 5 prostheses being removed. All 6 patients had a history of urinary tract infection. Furthermore, all 6 patients had either a neurogenic bladder (4), diabetes (1) or an ileal conduit (1), which increased the risk of a urinary tract infection. Cultures of the infected prostheses revealed only enteric organisms. No staphylococci were cultured...

LAPAROSCOPIC BURCH BLADDER NECK SUSPENSION: EARLY RESULTS

PURPOSE The Burch suspension is an effective treatment for stress urinary incontinence due to hypermobility. To decrease the associated morbidity and hospital stay, we attempted the procedure laparoscopically in 46 women. MATERIALS AND METHODS All patients had stress incontinence with bladder neck hypermobility. Preoperative testing included cystoscopy, multichannel urodynamics with pressure-flow studies and measurement of Valsalva leak point pressure. Mean patient age was 49.5 years (range 26 to 70). RESULTS In 12 patients the laparoscopic approach could not be completed and an open operation was performed. Of the 34 laparoscopic Burch procedures 13 were performed transperitoneally and 21 extraperitoneally. Mean operative time was 196 minutes (range 130 to 300), mean blood loss 96.3 cc (range 50 to 400) and mean postoperative hospital stay 3.2 days (range 1 to 8). Five postoperative complications included hematoma/anemia in 2 patients, transient urinary retention in 1, enterocele in 1 and uterine prolapse in 1. Mean followup was 17.3 months (range 12 to 26). Of the 34 patients only 5 had persistent incontinence postoperatively (3 with stress and urge incontinence, 1 with stress incontinence only and 1 with urge incontinence only). Overall, 85% of the patients are totally dry. With experience the operative time and postoperative stay decreased. The extraperitoneal and transperitoneal approaches provide certain advantages. CONCLUSIONS The Burch suspension performed laparoscopically appears to have a favorable morbidity profile with a successful continence outcome. However, there is a steep learning curve to the procedure as manifested by the long operative time.

Fascial Slings and Bladder Neck Tapering in the Treatment of Male Neurogenic Incontinence

Intractable incontinence in selected male patients with a neurogenic bladder has been treated by increasing bladder compliance with augmentation cystoplasty and increasing urethral resistance with the artificial urinary sphincter. However, there are a number of complications associated with the use of an artificial urinary sphincter. As an alternative, we performed bladder neck tapering and bladder neck slings in 13 men with a neurogenic bladder and an incompetent urethra (10 with spina bifida and 3 with spinal cord injury) undergoing bladder augmentation. Mean patient age was 27 years (range 17 to 40 years) and mean followup was 34.3 months (range 5.5 to 49 months). Postoperatively, there was a 113% increase in mean bladder capacity (from 260 to 550 cc) and a 62% decrease in mean bladder pressure at capacity (from 53 to 20 cm. water). The earliest 2 patients with a Marlex sling suffered erosions that were treated with transurethral excision. As a result, the 11 subsequent patients had a rectus fascial sling. Nine patients (69.2%) are completely dry on self-catheterization, 2 (15.4%) required collagen injections for improved continence and 2 failures (15.4%) required additional procedures. The complications in these patients are comparable to, if not better than, the use of an artificial urinary sphincter. We conclude that a fascial sling with bladder neck tapering is an excellent alternative to the artificial urinary sphincter in the treatment of male neurogenic bladder with an incompetent urethra.

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.

Intraoperative floppy-iris syndrome during cataract surgery in men using alpha-blockers for benign prostatic hypertrophy

A small-pupil syndrome called intraoperative floppy-iris syndrome (IFIS) inmen taking a1A-receptor blockers (namely, tamsulosin hydrochloride) for benign prostatic hypertrophy (BPH) was described by Chang and Campbell in 2005 (D.F. Chang, MD, J.R. Campbell, MD, ‘‘A New Small Pupil Syndrome Caused by Flomax,’’ EyeWorld, January 2005, page 50). This syndrome is characterized by a triad of flaccid iris stroma that causes intraoperative billowing, propensity of the iris to prolapse, and progressive intraoperative miosis. Following Chang and Campbell’s description, there has been increased awareness of this syndrome among cataract surgeons and in the urological literature. The purpose of this study was to assess the occurrence of IFIS during cataract surgery in men on all systemic a-blockers at a university teaching hospital in Toronto, Canada.

Urodynamic findings in adults with the tethered cord syndrome.

PURPOSE We evaluated bladder function in adults with the tethered cord syndrome using multichannel urodynamics. MATERIALS AND METHODS A total of 21 patients a mean 39.6 years old (range 20 to 62) with a tethered cord were evaluated. Of the patients 13 were diagnosed with a tethered cord as an adult and 8 had undergone previous spinal surgery. The tethered cord syndrome was diagnosed by magnetic resonance imaging in 20 patients and computerized tomography myelogram in 1. All patients underwent complete neurological and urological evaluation, including multichannel urodynamics. Needle electromyography and video urodynamics were performed in select cases. Microsurgical release of the tethered cord was performed in 19 patients and 2 refused surgery. Urodynamics were done before surgery in 16 of 19 patients and a median of 12.5 months (range 1 to 40) after surgery in 14. In addition, intraoperative urodynamic monitoring and nerve root stimulation were done in 14 patients to prevent nerve root injury at surgery. RESULTS At presentation urgency (67%) and urge incontinence (50%) were the most common findings in 18 patients with urinary symptoms. Pretreatment urodynamics in 18 of 21 patients revealed hyperreflexia in 13 (72%), external detrusor-sphincter dyssynergia in 4 (22%), decreased sensation in 4 (22%), decreased compliance in 3 (17%) and hypocontractile detrusor in 2 (11%). Postoperative urodynamic findings were improved in 4 patients (29%) and unchanged in 10 (71%). Preoperative external detrusor-sphincter dyssynergia in 4 patients resolved postoperatively in 3 and was unchanged in 1. Urinary symptoms were improved in 19% of patients (4), unchanged in 76% (16) and worse in 5% (1). To date 7 patients require anticholinergics, 4 require clean intermittent catheterization and 1 is taking an alpha-blocker. CONCLUSIONS Adults with the tethered cord syndrome are less likely to have urodynamic or symptom improvement after cord release and most often present with irreversible findings which rarely become worse after surgery. These patients need to have careful and continuous followup, including urodynamic studies, due to possible re-tethering with time.