Andrew Peterson

MP26-02 DIFFERENTIAL RESPONSIVENESS TO NEUROSTIMULATION ACROSS THE BLADDER FILLING CYCLE IN RODENTS

mRNA expression profiles associated with different states of BOOinduced LUTD in human patients. Animal models of experimentallyinduced partial BOO are widely used to study bladder wall remodeling. Here we determined the expression profiles of miRNAs and selected mRNAs in pBOO mice and compared the observed changes to human patients. METHODS: All experiments were performed using 10-to-12week-old male mice that underwent microsurgical creation of pBOO and sham-operated control animals. Bladders were harvested 2, 4, 6 and 8 weeks after pBOO and total RNA isolated. Muscle contractility was assessed in parallel cohorts at 1, 2, 4 and 6 weeks. Expression profiles of 598 miRNAs were established using NanoString nCounter Analysis System mouse miRNA assay kit. Levels of selected mouse mRNAs were determined by QPCR. Bladder dome biopsies were collected from controls and patients with urodynamically established BOO and miRNA and mRNA expression profiles determined by Next Generation Sequencing (NGS) analysis. RESULTS: Similar to human patients0 results, we observed a down-regulation of smooth muscle-associated miRNAs mmu-miR-1, mmu-miR-143, mmu-miR-145, mmu-miR-486 and mmu-miR-133a in pBOO mouse bladders. Pro-fibrotic mmu-miR-142-3p and mmumiR-21 were up-regulated, and anti-fibrotic mmu-miR-29c downregulated. Surprisingly, the expression levels of other miRNAs including miR-22, -26b, -10a and -342-3p, which were strongly regulated in human BOO patients, did not change in the mouse model. Pathway analysis in human BOO patients identified TNFalpha as the top upstream regulator, and revealed signalling molecules, including MYC, FOS, CTGF, PIK3R5, which were strongly induced in different urodynamic states of BOO. In pBOO mice there was evidence of hypertrophic changes (MYBL2, MYH11 and MYC up-regulation) at 2 weeks pBOO, and CTGF was significantly increased at 4 and 6 weeks post-obstruction. Contrary to human data, we observed no regulation of TNF-responsive genes in the mouse model. CONCLUSIONS: Experimentally-induced pBOO in mice led to significant gene expression changes, including alteration of pro-fibrotic mRNAs and miRNAs resembling human BOO patients. Lack of evidence of TNF-alpha-induced miRNA and mRNA regulation might indicate a different pathophysiological mechanism of organ remodelling in pBOO model compared to human disease.

MP69-02 VARIATION IN CARE INTENSITY FOR OVERACTIVE BLADDER SYMPTOMS AMONG MEDICARE BENEFICIARIES

INTRODUCTION AND OBJECTIVES: Overactive bladder (OAB) is characterized by urinary urgency, frequency, nocturia, and urinary incontinence (UI). The prevalence of OAB increases significantly with age. The first-line therapy for OAB is antimuscarinic medication, some of which have deleterious side-effects, including cognitive decline. We sought to examine the incidence and prevalence of antimuscarinic prescriptions among elderly persons 1⁄4 age 65. METHODS: The 2006-12 National Ambulatory Medical Care Survey (NAMCS) were queried for patients with newly given or renewed prescriptions for any of 6 antimuscarinics: oxybutynin, tolterodine, fesoterodine, darifenacin, solifenacin, and trospium. Within these cohorts, frequencies of patient/physician attributes and annual trends in drug prescription were determined utilizing drug-mention weighting methodology. RESULTS: A weighted estimate of 47.68 million individuals (unweighted n1⁄41,968) had their antimuscarinics renewed, and 12.77 million patients (unweighted n1⁄4641) received a new prescription (Table 1). The majority of new antimuscarinics were prescribed in elderly (1⁄4 age 65) (55.2%), female (69.2%), white (61.7%), and Medicare insured (84.1%) individuals. Oxybutynin was a frequently prescribed (incidence 27.3%) and continued (prevalence 33.2 %) antimuscarinic among elderly patients. In 2010, there was a sharp decrease in the number of all continued antimuscarinic prescriptions, followed by annual increases in oxybutynin continuation versus continued decline in other antimuscarinic continuation (Figure 1). Figure 1: Continued Antimuscarinic Prescriptions in Patients > 65 Years of Age, NAMCS 2006-2012 CONCLUSIONS: We found alarmingly high prescription rates of oxybutynin (27.3%), pharmacologically the least suitable antimuscarinic, for which studies have consistently demonstrated higher rates of cognitive impairment in the elderly. Frequent oxybutynin prescription is likely driven by tiered Medicare formularies which require patients to trial oxybutynin, a cheaper, generic antimuscarinic, before allowing access to newer, more costly yet safer, antimuscarinics. This work is the first population-based study demonstrating both the alarming rate of oxybutynin prescription and the lack of a proper safety net for a growing and vulnerable elderly population. Our work demands an increased consideration of the possible deleterious effects of unmonitored antimuscarinic use in elderly patients. Source of Funding: none

MP46-18 A LOGISTIC REGRESSION PREDICTION MODEL FOR THE SUCCESS OF THE MALE TRANSOBTURATOR SLING; VALSALVA LEAK-POINT PRESSURE (VLPP) GREATER THAN 70 CM H2O IS AN INDICATOR FOR SLING SUCCESS

INTRODUCTION AND OBJECTIVES: Male stress urinary incontinence (SUI) is a common sequela of radical prostatectomy and occasionally benign prostatic hyperplasia surgery, causing significant impact on quality of life. The AdVance transobturator sling has been described as a safe and effective minimally invasive treatment for male SUI, but early postoperative urinary retention (EPUR) is not uncommon. This study evaluates the outcomes of patients who have EPUR after insertion of an AdVance transobturator male sling for treatment of SUI. Our hypothesis is that although EPUR can be concerning, it is usually transient and may be associated with favorable continence outcomes. METHODS: A review of all men with SUI treated with an AdVance transobturator sling by a single surgeon during the period of January 1, 2006 through August 1, 2016, was performed. Perioperative, continence and complication outcomes (including urinary retention, mesh erosion and reoperation) were assessed. Outcomes of men who experienced EPUR were compared with men who did not experience EPUR. Statistical analyses such as Chi Square test were performed in Microsoft Excel 2016. RESULTS: 257 men (mean age 68 years) underwent insertion of a transobturator sling for SUI during the study period. Mean follow up was 25 months; 5 men were lost to follow up. Overall, success rate was 84%, with 45% (114/252) of men reporting complete continence and 39% (98/252) reporting improvement only. Overall, the mean number of pads used per patient per day improved from 3.7 pre-sling to 1.3 post-sling insertion. 16% (41/252) of patients experienced EPUR which was treated with reinsertion of indwelling Foley urethral catheter and repeat void trial. Most cases of urinary retention resolved within weeks; one patient required explantation of the sling due to ongoing urinary retention beyond 3 months. In the group of patients who had EPUR, success rate was 98%, with 61% of men achieving complete continence and 37% reporting improvement only. By comparison, in the group of patients who did not have EPUR, success rate was 82%, with 42% of men reporting complete continence and 39% of men stating improvement only. The difference in continence success rate between the EPUR and no EPUR groups was statistically significant (p<0.05). CONCLUSIONS: Insertion of an AdVance transobturator sling for treatment of male SUI was complicated by EPUR in 16% of men. Most cases of EPUR were transient. The continence success rate in the group of men who experienced EPUR was significantly better than in the group of men without EPUR.