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    Linda Brubaker

    Anticholinergic medications and onabotulinumtoxinA are used to treat urgency urinary incontinence, but data directly comparing the two types of therapy are needed. We performed a double-blind, double-placebo-controlled, randomized trial... more
    Anticholinergic medications and onabotulinumtoxinA are used to treat urgency urinary incontinence, but data directly comparing the two types of therapy are needed. We performed a double-blind, double-placebo-controlled, randomized trial involving women with idiopathic urgency urinary incontinence who had five or more episodes of urgency urinary incontinence per 3-day period, as recorded in a diary. For a 6-month period, participants were randomly assigned to daily oral anticholinergic medication (solifenacin, 5 mg initially, with possible escalation to 10 mg and, if necessary, subsequent switch to trospium XR, 60 mg) plus one intradetrusor injection of saline or one intradetrusor injection of 100 U of onabotulinumtoxinA plus daily oral placebo. The primary outcome was the reduction from baseline in mean episodes of urgency urinary incontinence per day over the 6-month period, as recorded in 3-day diaries submitted monthly. Secondary outcomes included complete resolution of urgency urinary incontinence, quality of life, use of catheters, and adverse events. Of 249 women who underwent randomization, 247 were treated, and 241 had data available for the primary outcome analyses. The mean reduction in episodes of urgency urinary incontinence per day over the course of 6 months, from a baseline average of 5.0 per day, was 3.4 in the anticholinergic group and 3.3 in the onabotulinumtoxinA group (P=0.81). Complete resolution of urgency urinary incontinence was reported by 13% and 27% of the women, respectively (P=0.003). Quality of life improved in both groups, without significant between-group differences. The anticholinergic group had a higher rate of dry mouth (46% vs. 31%, P=0.02) but lower rates of catheter use at 2 months (0% vs. 5%, P=0.01) and urinary tract infections (13% vs. 33%, P<0.001). Oral anticholinergic therapy and onabotulinumtoxinA by injection were associated with similar reductions in the frequency of daily episodes of urgency urinary incontinence. The group receiving onabotulinumtoxinA was less likely to have dry mouth and more likely to have complete resolution of urgency urinary incontinence but had higher rates of transient urinary retention and urinary tract infections. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institutes of Health Office of Research on Women's Health; ClinicalTrials.gov number, NCT01166438.).
    Emerging evidence challenges the long-held paradigm that the healthy bladder is sterile. These discoveries may provide new opportunities to address important women's health conditions, which include preterm labor and delivery, urinary... more
    Emerging evidence challenges the long-held paradigm that the healthy bladder is sterile. These discoveries may provide new opportunities to address important women's health conditions, which include preterm labor and delivery, urinary tract infections, and common forms of urinary incontinence. Traditional tools for urinary bacterial assessment, which includes urinary dipsticks and standard urine cultures, have significant limitations that restrict the information that is available to clinicians. For example, the standard urine culture does not detect slow-growing bacteria that die in the presence of oxygen. Two new, complementary tools, however, can detect these and other organisms, which permits a more complete characterization of bacterial communities within the female bladder. Obstetrician-gynecologists should become familiar with these new approaches (expanded quantitative urine culture and 16S ribosomal RNA gene sequencing) that can detect previously unrecognized organisms....
    OBJECTIVES: (1) to describe sexual function in women seeking treatment of stress urinary incontinence (SUI); (2) to compare the impact on sexual function of three SUI treatments; and (3) to investigate whether non-surgical treatment of... more
    OBJECTIVES: (1) to describe sexual function in women seeking treatment of stress urinary incontinence (SUI); (2) to compare the impact on sexual function of three SUI treatments; and (3) to investigate whether non-surgical treatment of SUI is associated with improved sexual function. METHODS: Women with SUI were randomized to continence pessary, behavioral therapy (pelvic floor muscle training and continence strategies), or combination therapy. Sexual function was assessed at baseline and 3-months using short forms of the Pelvic Organ Prolapse-Urinary Incontinence Sexual Function Questionnaire (PISQ-12) and the Personal Experiences Questionnaire (SPEQ). Successful treatment of SUI was assessed with a patient global impression of improvement. ANOVA was used to compare scores between groups. RESULTS: At baseline, sexual function was worse among women with mixed incontinence compared to those with pure SUI. After therapy, successful treatment of SUI was associated with greater improvement in PISQ-12 score (2.26 ± 3.24 versus 0.48 ± 3.76, p=0.0007), greater improvement in incontinence with sexual activity (0.45 ± 0.84 versus 0.01 ± 0.71, p=0.0002), and greater reduction in restriction in sexual activity related to fear of incontinence (0.32 ± 0.76 versus -0.06 ± 0.78, p=0.0008). Among those successfully treated for SUI, improvement in continence during sexual activity was greater in both the combined therapy group (p=0.019) and the behavioral group (p=0.02) compared to the pessary group. CONCLUSIONS: Successful non-surgical treatment of SUI is associated with improvements in incontinence-specific measures of sexual function. Behavioral therapy may be preferred to pessary for treatment of SUI among women whose incontinence interferes with sexual function.
    We aimed to explore operational definitions of mixed urinary incontinence (MUI) for use in incontinence outcomes research for non-surgical patient populations. A secondary analysis of women with urge incontinence or urge predominant MUI... more
    We aimed to explore operational definitions of mixed urinary incontinence (MUI) for use in incontinence outcomes research for non-surgical patient populations. A secondary analysis of women with urge incontinence or urge predominant MUI enrolled in the Urinary Incontinence Treatment Network BE-DRI randomized clinical trial was performed. Subjects were characterized at baseline for urinary incontinence severity and incontinence subtype (stress or urge) using the Medical, Epidemiologic, and Social Aspects of Aging (MESA) questionnaire, the Urogenital Distress Inventory, and a 7-day urinary diary. Various different definitions of MUI, ranging from low to high threshold, were created using a combination of these baseline incontinence measures. Prevalence of MUI based on each definition was described and compared to treatment response. Logistic regression analysis was used to estimate the association between the study outcomes and the different definitions of MUI. The 307 participants in...
    Human urinary disorders are generally studied in rodent models due to limitations of functional in vitro culture models of primary human urothelial cells (HUCs). Current HUC culture models are often derived from immortalized cancer cell... more
    Human urinary disorders are generally studied in rodent models due to limitations of functional in vitro culture models of primary human urothelial cells (HUCs). Current HUC culture models are often derived from immortalized cancer cell lines, which likely have functional characteristics differ from healthy human urothelium. Here, we described a simple explant culture technique to generate HUCs and assessed their in vitro functions. Using transmission electron microscopy, we assessed morphology and heterogeneity of the generated HUCs and characterized their intercellular membrane structural proteins relative to ex vivo urothelium tissue. We demonstrated that our cultured HUCs are free of fibroblasts. They are also heterogeneous, containing cells characteristic of both immature basal cells and mature superficial urothelial cells. The cultured HUCs expressed muscarinic receptors (MR1 and MR2), carnitine acetyltransferase (CarAT), immunoregulatory cytokines IL7, IL15, and IL23, as well...
    More than 300,000 surgeries are performed annually in the United States for pelvic organ prolapse. Sacrospinous ligament fixation (SSLF) and uterosacral ligament suspension (ULS) are commonly performed transvaginal surgeries to correct... more
    More than 300,000 surgeries are performed annually in the United States for pelvic organ prolapse. Sacrospinous ligament fixation (SSLF) and uterosacral ligament suspension (ULS) are commonly performed transvaginal surgeries to correct apical prolapse. Little is known about their comparative efficacy and safety, and it is unknown whether perioperative behavioral therapy with pelvic floor muscle training (BPMT) improves outcomes of prolapse surgery. To compare outcomes between (1) SSLF and ULS and (2) perioperative BPMT and usual care in women undergoing surgery for vaginal prolapse and stress urinary incontinence. Multicenter, 2 × 2 factorial, randomized trial of 374 women undergoing surgery to treat both apical vaginal prolapse and stress urinary incontinence was conducted between 2008 and 2013 at 9 US medical centers. Two-year follow-up rate was 84.5%. The surgical intervention was transvaginal surgery including midurethral sling with randomization to SSLF (n = 186) or ULS (n = 18...
    Anticholinergic medications and onabotulinumtoxinA are used to treat urgency urinary incontinence, but data directly comparing the two types of therapy are needed. We performed a double-blind, double-placebo-controlled, randomized trial... more
    Anticholinergic medications and onabotulinumtoxinA are used to treat urgency urinary incontinence, but data directly comparing the two types of therapy are needed. We performed a double-blind, double-placebo-controlled, randomized trial involving women with idiopathic urgency urinary incontinence who had five or more episodes of urgency urinary incontinence per 3-day period, as recorded in a diary. For a 6-month period, participants were randomly assigned to daily oral anticholinergic medication (solifenacin, 5 mg initially, with possible escalation to 10 mg and, if necessary, subsequent switch to trospium XR, 60 mg) plus one intradetrusor injection of saline or one intradetrusor injection of 100 U of onabotulinumtoxinA plus daily oral placebo. The primary outcome was the reduction from baseline in mean episodes of urgency urinary incontinence per day over the 6-month period, as recorded in 3-day diaries submitted monthly. Secondary outcomes included complete resolution of urgency urinary incontinence, quality of life, use of catheters, and adverse events. Of 249 women who underwent randomization, 247 were treated, and 241 had data available for the primary outcome analyses. The mean reduction in episodes of urgency urinary incontinence per day over the course of 6 months, from a baseline average of 5.0 per day, was 3.4 in the anticholinergic group and 3.3 in the onabotulinumtoxinA group (P=0.81). Complete resolution of urgency urinary incontinence was reported by 13% and 27% of the women, respectively (P=0.003). Quality of life improved in both groups, without significant between-group differences. The anticholinergic group had a higher rate of dry mouth (46% vs. 31%, P=0.02) but lower rates of catheter use at 2 months (0% vs. 5%, P=0.01) and urinary tract infections (13% vs. 33%, P<0.001). Oral anticholinergic therapy and onabotulinumtoxinA by injection were associated with similar reductions in the frequency of daily episodes of urgency urinary incontinence. The group receiving onabotulinumtoxinA was less likely to have dry mouth and more likely to have complete resolution of urgency urinary incontinence but had higher rates of transient urinary retention and urinary tract infections. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institutes of Health Office of Research on Women's Health; ClinicalTrials.gov number, NCT01166438.).
    Midurethral slings are increasingly used for the treatment of stress incontinence, but there are limited data comparing types of slings and associated complications. We performed a multicenter, randomized equivalence trial comparing... more
    Midurethral slings are increasingly used for the treatment of stress incontinence, but there are limited data comparing types of slings and associated complications. We performed a multicenter, randomized equivalence trial comparing outcomes with retropubic and transobturator midurethral slings in women with stress incontinence. The primary outcome was treatment success at 12 months according to both objective criteria (a negative stress test, a negative pad test, and no retreatment) and subjective criteria (self-reported absence of symptoms, no leakage episodes recorded, and no retreatment). The predetermined equivalence margin was +/-12 percentage points. A total of 597 women were randomly assigned to a study group; 565 (94.6%) completed the 12-month assessment. The rates of objectively assessed treatment success were 80.8% in the retropubic-sling group and 77.7% in the transobturator-sling group (3.0 percentage-point difference; 95% confidence interval [CI], -3.6 to 9.6). The rat...
    Minimum important difference (MID) estimates the minimum degree of change in an... more
    Minimum important difference (MID) estimates the minimum degree of change in an instrument's score that correlates with a patient's subjective sense of improvement. We aimed to determine the MID for the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) using both anchor based and distribution based methods derived using data from the Trial of Midurethral Slings (TOMUS). Instruments for the anchor-based analyses included the urogenital distress inventory (UDI), incontinence impact questionnaire (IIQ), patient global impression of improvement (PGI-I), incontinence episodes (IE) on 7-day bladder diary, and satisfaction with surgical results. After confirming moderate correlation (r ≥ 0.3) of ICIQ-UI SF and each anchor, MIDs were determined by calculating the difference between the mean instrument scores for individuals with the smallest amount of improvement and with no change. The distribution-based method of MID assessment was applied using effect sizes of 0.2 and 0.5 SD (small to medium effects). Triangulation was used to examine these multiple MID values in order to converge on a small range of values. Anchor-based MIDs range from -4.5 to -5.7 at 12 months and from -3.1 to 4.3 at 24 months. Distribution-based MID values were lower. Triangulation analysis supports a MID of -5 at 12 months and -4 at 24 months. The recommended MIDs for ICIQ-UI SF are -5 at 12 months and -4 at 24 months. In surgical patients, ICIQ-UI SF score changes that meet these thresholds can be considered clinically meaningful. Neurourol. Urodynam. 34:183-187, 2015. © 2013 Wiley Periodicals, Inc.
    Following transvaginal mesh, synthetic slings to correct stress urinary incontinence have been put under further scrutiny. Since the recent FDA website update, we reviewed the latest developments and then reflected on the lessons learned... more
    Following transvaginal mesh, synthetic slings to correct stress urinary incontinence have been put under further scrutiny. Since the recent FDA website update, we reviewed the latest developments and then reflected on the lessons learned by applying this process and the way forward.
    We sought to describe change in sexual function 2 years after surgery to treat stress urinary incontinence. This analysis included 655 women randomized to Burch colposuspension or sling surgery. Sexual activity was assessed by the Pelvic... more
    We sought to describe change in sexual function 2 years after surgery to treat stress urinary incontinence. This analysis included 655 women randomized to Burch colposuspension or sling surgery. Sexual activity was assessed by the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) among those sexually active at baseline and 2 years after surgery. Mean PISQ-12 total score improved from baseline 32.23 +/- 6.85 to 36.85 +/- 5.89. After surgery, fewer subjects reported incontinence (9% vs 53%; P < .0001), restriction of sexual activity as a result of fear of incontinence (10% vs 52%; P < .0001), avoidance of intercourse because of vaginal bulging (3% vs 24%; P < .0001), or negative emotional reactions during sex (9% vs 35%; P < .0001). Women with successful surgery had greater improvement PISQ-12 scores (5.77 vs 3.79; P < .006). Sexually active women were younger, thinner, and had lower Medical, Epidemiological, and Social Aspects of Aging scores (total and urge subscale) than sexually inactive women. Sexual function improves after successful surgery and does not differ between Burch and sling.