Vol. 181, No. 4, Supplement, Tuesday, April 28, 2009548 THE JOURNAL OF UROLOGY®

changes in fluid intake and incontinence over a 10-week study period. METHODS: In the Behavioral Enhances Drug Reduction

of Incontinence (BE-DRI) trial, women with predominant UUI were randomized to daily treatment with tolterodine or tolterodine combined with behavioral therapies among which were individualized fluid management instructions. Subjects in both groups received general fluid management instructions, while in the drug + behavior arm, those with excessive urine output (>2100ml/day) had additional individualized instruction during each of 4 study visits to learn behavioral strategies. Variables measured at baseline and at 10 weeks were: type of incontinence using the MESA, severity of incontinence by number of incontinence episodes based on a 7 day-diary, number of voids per 24h (F24), urgency rating, 24h fluid intake (I24) and 24 hr volume voided (V24), pad use, bothersomeness of UUI (UDI and OAB-q), and quality of life (IIQ-7, SF-12).

RESULTS: Based on t tests, mean leakage episodes per 24 hours, V24, I24, average urgency ratings and the percentage of voids, accidents or both with severe urgency all significantly decreased from baseline to 10 weeks (p<0.001 for each). Mean number of voids per 24 hours were higher in the drug group (mean 7.7, SD 2.5) than the drug + behavior group (mean 6.9, SD 1.7) at 10 weeks (p<0.001). In a multivariable model, treatment group was not associated with change in V24 from baseline to 10 weeks (p=0.8), but the difference in the number of accidents/diary day, F24, I24 and average voids/day each were positively related with the change in V24 (p<0.001 for each). Participants did demonstrate a response to fluid management instructions: there was a higher chance of a woman reporting >2100 ml of V24 at baseline and then 2100 ml or less of V24 at 10 weeks than reporting low V24 at baseline, but high V24 at 10 weeks (p= 0.011 McNemar’s test).

CONCLUSIONS: General fluid instructions may contribute to the reduction in UUI symptoms for women taking anticholinergic medications, but additional individualized instructions along with other behavioral therapies did little to improve outcome further.

Source of Funding: NIH U01DK60395-01

1531BOWEL AND PELVIC SYMPTOMS IMPROVE AFTER SACRAL NEUROMODULATION FOR OVERACTIVE BLADDER: THE PRELIMINARY RESULTS

Mia A Swartz*, Howard B Goldman, Wesley G Kong, Raymond R Rackley, Courtenay Moore, Sandip Vasavada, Brooke Gurland, Cleveland, OH

INTRODUCTION AND OBJECTIVES: Sacral neuromodulation (SNM) therapy was approved for treatment of overactive bladder (OAB) in 1997. In other countries, its application includes treatment of constipation and fecal incontinence. The exact mechanism of this effect is currently unknown, and SNM could theoretically affect the bowels and pelvic floor in patients undergoing implantation for urinary indications. Thus, our goal was to describe any changes in bowel function and pelvic symptoms that occur after SNM in patients with refractory OAB.

METHODS: We prospectively enrolled women with refractory OAB undergoing SNM. A baseline standardized intake questionnaire and physical were performed. Where possible, an anticholinergic washout was completed (N=19). We administered the Pelvic Floor Distress Inventory-20 which contains several domains: Pelvic Organ Prolapse Distress Inventory-6(POPDI-6), Colorectal-Anal Distress Inventory-8(CRADI-8) and the Urogenital Distress Inventory-6 (UDI-6). A corresponding quality-of-life (QOL) questionnaire, the Pelvic Floor Impact Questionnaire-7 with domains for pelvic (POPIQ-7), bowel (CRAIQ-7) and urinary symptoms (UIQ-7) was filled out. Scores for each domain range from 0-100 with higher scores indicating worse symptoms or QOL.

RESULTS: Twenty-three women (mean age 58 years) had complete pre- and postoperative questionnaires. Sixteen (70%) were taking bowel medication including laxatives (50%), fiber (31%), mixed medication (31%), stool softener (19%), enemas (13%) and antidiarrheals (19%). By the end of test stimulation, mean baseline scores decreased from 22.3 to 14.6 (POPDI-6), 35.2 to 22.8 (CRADI-8), 55 to 31 (UDI-6), and 111 to 68 (PFDI-20). These improvements were significant for total

PFDI-20 score (p<0.001) and all of its domains (p<0.01 for POPDI-6 and p<0.001 for CRADI-8 and UDI-6). Significant improvements were noted in corresponding QOL for CRAIQ-7 (p=0.03), UIQ-7 (p<0.01) and total PFIQ-7 (p=0.02), but not for POPIQ-7 domain. Ten patients available for 3 month follow-up showed continued significant improvement in all pelvic symptom scores and corresponding QOL parameters.

CONCLUSIONS: We have documented considerable bowel and pelvic symptoms at baseline in the refractory OAB population. Sacral neuromodulation appears to significantly improve these symptoms and QOL. Given the apparent bowel dysfunction in this refractory population, SNM therapy may be more appropriate than anticholinergic treatment or botulinum toxin injections.

Source of Funding: None

1532INSTILLATION OF BOTULINUM A TOXIN (BTX)/DIMETHYL SULFOXIDE (DMSO) BLADDER SOLUTION FOR THE TREATMENT OF VOIDING DYSFUNCTION SECONDARY TO DETRUSOR OVERACTIVITY (DO) IN WOMEN: A PHASE I/II STUDY

Steven P Petrou, David D Thiel, Alexandra E Rogers*, Alexander S Parker, Julia E Crook, Jacksonville, FL

INTRODUCTION AND OBJECTIVES: Injection of BTX into the detrusor muscle has been successful in treating women with DO; however, this procedure requires endoscopic delivery under anesthesia and has only short term efficacy. Motivated by this, we conducted a Phase I/II trial to evaluate the safety and efficacy of direct instillation of a BTX/DMSO solution into the bladder via a urethral catheter as a means of treating DO in women.

METHODS: We enrolled 25 women with urodynamic-confirmed DO who failed at least two anticholenergic therapies. The first 3 patients were given a 66% dosing of solution (Phase I); the final 22 patients (Phase II) received the full 300 units of Botox and 50 cc of DMSO (50% concentration). Adverse events (AE) were evaluated up to three months after treatment. We collected the following measures at baseline and at one and three months following treatment: 24 hour pad weights & incontinence episodes, post void residuals (PVR), and scores on the Blaivas-Groutz, IUSS, IIQ-7, UDI-6 and I-QOL questionnaires.

RESULTS: There were no serious adverse events or clinically significant increases in PVR. Of the 22 women enrolled in Phase II, one withdrew for reasons unrelated to the study. Among the 21 completers, we noted a reduction in median 24hr pad weight from baseline (135g) to 1 month (46g; p= 0.21) and three months (55g; p= 0.43). Median number of incontinence episodes decreased from 4 at baseline to 2 at one month (p=0.004); it returned to 4 at three months (p=0.81). Median scores improved from baseline to one month on the IIQ-7 (13 to 7; p=0.007), UDI (10 to 6; p=0.003) and I-QOL (45 to 79; p<0.001); similar improvements were evident at three months (all p 0.002). While 11 women (52%) reported severe urgency based on the IUSS score at baseline, only 1 (5%, p<0.001) and 3 (14%, p=0.004) reported severe scores at one and three months, respectively. Based on the BG score, 16 (76%) women reported severe incontinence at baseline; this dropped to 10 (48%) at one month and 13 (62%) at three months (p=0.005 and 0.22, respectively).

CONCLUSIONS: Direct instillation of BTX/DMSO solution is a safe and promising means of treating women with DO. Our observed improvements compare well with previous series of cystoscopically injected BTX. As such, our study demonstrates the potential of a minimally-invasive therapy for female DO patients and provides the rationale for further evaluation of this novel technique in a randomized, placebo controlled phase III setting.

Source of Funding: N/A