A prospective, randomized trial comparing intravesical dimethyl sulfoxide (DMSO) to bupivacaine, triamcinolone, and heparin (BTH), for newly diagnosed interstitial cystitis/painful bladder syndrome (IC/PBS).

INTRODUCTION AND HYPOTHESIS: The primary aim of this study was to compare the effect of bladder instillations using dimethyl sulfoxide (DMSO) with triamcinolone versus bupivacaine, triamcinolone, and heparin (BTH) in women with newly diagnosed interstitial cystitis/painful bladder syndrome. The primary outcome was improvement in symptoms measured using the O'Leary-Sant Interstitial Cystitis Symptoms Index (ICSI) score. Secondary comparisons included changes in urinary frequency, nocturia, and bladder capacity. MATERIALS AND METHODS: This was a prospective, randomized study. Patients with a recent diagnosis of interstitial cystitis/painful bladder syndrome (IC/PBS) were randomized 1:1 to treatment with either 6 weekly bladder instillations of DMSO with triamcinolone or BTH. During follow-up visits, patients completed the ICSI questionnaire, and bladder capacity was determined through the retrograde filling of the bladder. The χ2 test or Student's t test were used for data analysis. RESULTS: A total of 83 patients were randomized, and final analysis included 70 participants who completed the 6 weekly instillations (42 DMSO, 28 BTH). The groups were similar in baseline demographics and clinical characteristics, except for cystometric maximum capacity (DMSO 338.62± 139.44 mL, BTH 447.43 ± 180.38 mL, p = 0.01). In the DMSO group, 63% of patients had a greater than 29.5% reduction in total ICSI score versus 43% in the BTH group (p = 0.15). Nocturia and pain were significantly reduced in the DMSO group. There was a significant increase from baseline in bladder capacity for both groups. CONCLUSION: In women with newly diagnosed IC/PBS, bladder instillations with DMSO and triamcinolone provide greater improvement in pain and nocturia compared to BTH.

The female urethra: urethral function throughout a woman's lifetime.

INTRODUCTION AND HYPOTHESIS: The objective of this narrative review is to describe changes in urethral function that occur during a woman's lifetime. Evaluation of urethral function includes measurements of urethral closure pressure, at rest and during stress, leak point pressure, and the detailed study of anatomical and histological changes of the urethral sphincteric mechanism. METHODS: A literature search in MEDLINE, PubMed, and relevant journals from 1960 until 2020 was performed for articles dealing with urethral function and the impact of aging, pregnancy, and childbirth, female hormones, and menopausal transition on the urethral sphincteric mechanism. Longitudinal and cross-sectional epidemiological surveys, studies on histological changes in urethral anatomy during aging, and urodynamic data obtained at different points in a woman's lifetime, during pregnancy, after childbirth, as well as the effects of female hormones on urethral sphincter function are reviewed. Relevant studies presenting objective data are analyzed and briefly summarized. RESULTS AND CONCLUSIONS: The findings lead one to conclude that a constitutional or genetic predisposition, aging, and senescence are the most prominent etiological factors in the development of urinary incontinence and other pelvic floor disorders. Vaginal childbirth dilates and may damage the compressed pelvic supportive tissues and is invariably associated with a decline in urethral sphincter function. Pregnancy, hormonal alterations, menopausal transition, weight gain, and obesity are at best of secondary influence on the pathology of lower urinary tract dysfunction. The decline of circulating estrogens during menopausal transition may play a role in the transition of fibroblasts to cellular senescence.

Feasibility of a Fully Implanted, Nickel Sized and Shaped Tibial Nerve Stimulator for the Treatment of Overactive Bladder Syndrome with Urgency Urinary Incontinence.

PURPOSE: We performed a clinical feasibility trial to evaluate the safety and efficacy of a fully implanted, primary battery powered, nickel sized and shaped neuromodulation device called the eCoin® for tibial nerve stimulation to treat refractory urgency urinary incontinence. MATERIALS AND METHODS: This prospective, single arm, open label study included 46 participants with refractory urgency urinary incontinence. It was performed at multiple sites in the United States and New Zealand. The device was implanted in the lower leg over the tibial nerve and activated after 4 weeks. Bladder diary data and validated quality of life instruments were collected 3 and 6 months after activation and compared to baseline values. RESULTS: The mean ± SD age of participants was 63.4 ± 11.5 years and 45 (98%) were female. Episodes of urgency urinary incontinence were reduced a relative median of 71% after 3 months of treatment (4.2 vs 1.7 daily episodes at 3 months, p = 0.001). A 50% or greater decrease in reported episodes of urgency urinary incontinence was observed in 32 of 46 participants (69.6%) at 3 months with more than 20% dry at 3 and 6 months. I-QOL (Incontinence Quality of Life) scores improved an average of 25.9 points and 33 of 46 patients (72%) indicated improvement in symptoms. A single serious adverse event secondary to wound care resolved with intravenous antibiotics. CONCLUSIONS: The implantable neuromodulation device was a safe and effective treatment of urgency urinary incontinence associated with overactive bladder syndrome with a significant reduction or resolution of symptoms and no significant safety concerns.

Predictors of successful percutaneous tibial nerve stimulation (PTNS) in the treatment of overactive bladder syndrome.

INTRODUCTION AND HYPOTHESIS: Multiple publications have demonstrated the efficacy of percutaneous tibial nerve stimulation (PTNS) for overactive bladder syndrome (OAB). However, patient characteristics associated with successful treatment have not been well established. The aim of this study was to identify prognostic factors for successful PTNS treatment. METHODS: This was a retrospective chart review of women who underwent PTNS therapy for OAB between January 2011-Decemeber 2017. Treatment success was defined by subjective improvement according to patient self-report and objective bladder diary parameters including the intervoiding interval, nocturia episodes and urgency urinary incontinence (UUI) episodes per day, before and after PTNS treatment. Baseline symptoms were dichotomized for each symptom based on severity. RESULTS: One hundred sixty-two women with a mean age of 72.7 ± 11.3 years and BMI of 28.5 ± 7.1 were included in the study. There was a statistically significant improvement in all three OAB symptoms after treatment. Multivariable analysis revealed that a history of depression and anxiety was associated with subjective improvement, whereas decreased subjective improvement was associated with a history of hypertension, prior intravesical onabotulinnumtoxinA injection and sacral neuromodulation. While dichotomizing subjects into two groups defined by < 50% versus ≥ 50% improvement, depression/anxiety, urodynamic volume at first sensation to void and more severe baseline urgency urinary incontinence severity were all significant predictors of subjective improvement. CONCLUSIONS: Among women treated with PTNS for refractory OAB, a history of depression/anxiety and severe baseline urgency urinary incontinence were positive predictors of a successful PTNS outcome.

Does physician specialty affect persistence to pharmacotherapy among patients with overactive bladder syndrome?

INTRODUCTION AND HYPOTHESIS: We compared persistence on overactive bladder (OAB) pharmacotherapy in patients treated in the Female Pelvic Medicine and Reconstructive Surgery (FPMRS) department compared with patients treated in the Internal Medicine (IM) and General Urology (GU) departments within an integrated health-care system. We hypothesized that persistence would be higher among FPMRS patients. METHODS: This was a retrospective cohort study. Patients with at least one prescription for OAB between January 2003 and July 2014 were identified. Demographic, prescription and treatment specialty data and data on the use of third-line therapies were collected. The primary outcome was persistence, defined as days on continuous pharmacotherapy. Discontinuation was defined as a treatment gap of ≥45 days. Discontinuation-free probabilities were calculated using the Kaplan-Meier method and compared among the specialties. Predictors of persistence were estimated using logistic regression with adjustment for covariates. Pearson correlation coefficients were calculated to identify risk associations. RESULTS: A total of 252 subjects were identified. At 12 weeks, 6 months and 1 year, FPMRS patients had the highest persistence rates of 93 %, 87 % and 79 % in contrast to 72 %, 68 % and 50 % in GU patients, and 83 %, 71 % and 63 % in IM patients (p = 0.006, p = 0.007, p = 0.001, respectively). The median persistence in FPMRS patients was 738 days, in GU patients 313 days and in IM patients 486 days (p = 0.006). Of the FPMRS patients, 61 % switched to at least a second medication, as compared to 27 % of IM patients and 14 % of GU patients (p < 0.0001). CONCLUSIONS: Persistence on OAB pharmacotherapy was higher among FPMRS patients than among GU and IM patients in this community setting. These results suggest that persistence is higher under subspecialist supervision.

Efficacy and safety of oxybutynin topical gel 3% in patients with urgency and/or mixed urinary incontinence: a randomized, double-blind, placebo-controlled study.

AIMS: To assess the efficacy and safety of oxybutynin transdermal gel 3% (OTG3%), with propylene glycol for enhanced skin permeation, in patients with urinary incontinence (UI). METHODS: In this phase 3 study, 626 patients ≥18 years old with urgency and/or mixed UI symptoms and predominantly urgency UI for ≥3 months were randomized 1:1:1 to receive 12 weeks of OTG3% 84 mg, OTG3% 56 mg, or placebo gel applied once daily to abdomen, inner/upper thigh, or upper arm/shoulder. Primary efficacy endpoint was change from baseline to Week 12 in weekly UI episodes recorded in 3-day bladder diaries. Results were compared using analysis of covariance. Adverse events (AEs) were monitored. RESULTS: Efficacy was assessed in 601 (intent-to-treat) and safety in 626 patients. At 12 weeks, OTG3% 84 mg/day achieved significantly greater improvement versus placebo in weekly UI episodes (mean change from baseline: -20.4 vs. -18.1; P < 0.05(a)), daily urinary frequency (-2.6 vs. -1.9; P = 0.001(b)), and urinary void volume (32.7 vs. 9.8; P < 0.0001(b)). Dry mouth, the most common treatment-related AE, occurred more often with OTG3% 84 mg/day (26/214 [12.1%]) vs. placebo (10/202 [5.0%]) (P = 0.028); 4 OTG3% patients withdrew because of dry mouth. Application site erythema occurred more often with OTG3% 84 mg/day (8/214 [3.7%]) versus placebo (2/202 [1.0%]) (P = NS); 12 OTG patients withdrew because of skin irritation. No serious treatment-related AEs occurred. CONCLUSIONS: OTG3% 84 mg/day was well tolerated and effective in improving urge incontinence or mixed UI symptoms with a predominance of UI in adults with overactive bladder.

Vesico-ureteral reflux in women with idiopathic high-pressure detrusor overactivity: prevalence, bladder function, and effect on the upper urinary tract.

INTRODUCTION AND HYPOTHESIS: To assess the prevalence of vesico-ureteral reflux (VUR) and upper urinary tract damage in women with idiopathic high-pressure detrusor overactivity (IHPDO) and to characterize their bladder function. METHODS: A retrospective chart review of women diagnosed with IHPDO (detrusor pressures > 40 cm H2O during involuntary bladder contractions) from 2007 to 2010 was conducted. Women were assessed for VUR by X-ray voiding cysto-urethrogram. Renal ultrasound or CT urogram, serum BUN/creatinine, and urinalyses were performed if reflux reached the renal pelvices. Cystometric and voiding pressure study data were reviewed for detrusor overactivity pressure and volume, voiding dysfunction, urethral relaxation, compliance, and bladder outlet obstruction. RESULTS: Sixty-five women were diagnosed with IHPDO, and 50 completed an X-ray voiding cysto-urethrogram. The median (range) detrusor overactivity pressure was 65 (41-251) cm H2O. Four (8.0%) women had IHPDO; none had upper urinary tract deterioration. The majority of women exhibited urethral relaxation with voiding, impaired compliance, and bladder outlet obstruction. CONCLUSIONS: Women with IHPDO are at risk of low-grade vesico-ureteral reflux. However, most women with IHPDO are likely protected from reflux by intermittent exposure to high detrusor pressures and the ability to decompress the bladder by urethral relaxation.

Cost effectiveness of radiofrequency microremodeling for stress urinary incontinence.

INTRODUCTION AND HYPOTHESIS: Stress urinary incontinence (SUI) is a common and growing problem among adult women and affects individuals and society through decreased quality of life (QoL), decreased work productivity, and increased health care costs. A new, nonsurgical treatment option has become available for women who have failed conservative therapy, but its cost effectiveness has not been evaluated. This study examined the cost effectiveness of transurethral radiofrequency microremodeling of the female bladder neck and proximal urethra compared with synthetic transobturator tape (TOT), retropubic transvaginal tape (TVT) sling, and Burch colposuspension surgeries for treating SUI. METHODS: A Markov model was used to compare the cost effectiveness of five strategies for treating SUI for patients who had previously failed conservative therapy. The strategies were designed to compare the value of starting with a less invasive treatment. The cost-effectiveness analysis was conducted from the health care system perspective. Efficacy and adverse event rates were obtained from the literature; reimbursement costs were based on Medicare fee schedule. The model cycle was 3 months, with a 3-year time horizon. Single-variable sensitivity analyses were conducted to assess stability of base-case results. RESULTS: Two of the five strategies employed the use of transurethral radiofrequency microremodeling and achieved 17-30 % lower mean costs relative to their comparative sling or Burch strategies. CONCLUSIONS: Superior safety and cost effectiveness are recognized when patients are offered a sequential approach to SUI management that employs transurethral radiofrequency microremodeling before invasive surgical procedures. This sequential approach is consistent with treatment strategies for other conditions and offers a solution for women with SUI who want to avoid the inherent risks and costs of invasive continence surgery.

Efficacy and safety of low dose desmopressin orally disintegrating tablet in women with nocturia: results of a multicenter, randomized, double-blind, placebo controlled, parallel group study.

PURPOSE: Previous studies suggest a lower dose of desmopressin orally disintegrating tablet may be effective in females compared to males with nocturia. We confirm the efficacy and safety of 25 µg desmopressin orally disintegrating tablet compared to placebo in female patients. MATERIALS AND METHODS: In this 3-month, randomized, double-blind, parallel group study 25 µg desmopressin once daily was compared to placebo in women with nocturia (2 or more nocturnal voids). The co-primary efficacy end points were change from baseline in mean number of nocturnal voids and proportion of patients achieving at least a 33% reduction from baseline in the mean number of nocturnal voids (33% responders). RESULTS: The full analysis set comprised 261 patients (age range 19 to 87 years). Desmopressin significantly reduced the mean number of nocturnal voids and increased the odds of a 33% or greater response compared to placebo during 3 months, assessed by longitudinal analysis (-0.22, p = 0.028 and OR 1.85, p = 0.006, respectively). Desmopressin increased the mean time to first nocturnal void by 49 minutes compared to placebo at 3 months (p = 0.003). The response to desmopressin was seen by week 1 of treatment and was sustained throughout the trial. Significant increases in health related quality of life and sleep quality were observed compared to placebo. Desmopressin was well tolerated. Serum sodium levels remained greater than 125 mmol/L throughout the trial and 3 transient decreases to less than 130 mmol/L were recorded. CONCLUSIONS: At a dose of 25 µg, desmopressin orally disintegrating tablet is an effective and well tolerated treatment for women with nocturia. Treatment provides rapid and sustained improvement in nocturia and quality of life.

Oxybutynin: past, present, and future.

Oxybutynin chloride is primarily indicated for the treatment of overactive bladder syndrome (OAB). It remains the most widely prescribed compound for OAB in the world. OAB is defined as the presence of urinary urgency, usually accompanied by daytime urinary frequency and nocturia, with or without urgency urinary incontinence, in the absence of infection or other identifiable etiology. This is a significant problem for men and women said to affect over 33 million adults in the USA, with the prevalence increasing with age. These symptoms can alter quality of life, with both physical and psychological impairment, as well as cause significant financial burden including the cost of sanitary supplies and decreased work productivity. Both pharmacological and non-pharmacological methods may be employed to aid in the treatment of OAB. The mainstay of treatment for OAB relies on pharmacological management, most specifically treatment with antimuscarinic medications. These medications are thought to prevent involuntary bladder contractions and/or urgency by inhibiting the muscarinic receptors within the urothelium and detrusor muscle. Currently, there are six different medications approved by the US Food and Drug Administration (FDA) for the treatment of OAB, with more than nine formulations including immediate- and extended-release tablets, transdermal patch and gel, vaginal ring, and suppository. This review will focus specifically on oxybutynin chloride, which has been used to treat OAB for four decades in numerous formulations.

Measuring the success of combined intravesical dimethyl sulfoxide and triamcinolone for treatment of bladder pain syndrome/interstitial cystitis.

INTRODUCTION AND HYPOTHESIS: The purpose of this study was to investigate change in bladder capacity as a measure of response to combined intravesical dimethyl sulfoxide (DMSO) and triamcinolone instillations for the treatment of newly diagnosed bladder pain syndrome/interstitial cystitis (BPS/IC). METHODS: 141 newly diagnosed women were identified retrospectively. 79 were treated with weekly DMSO/triamcinolone instillations. Change in bladder capacity with bladder retrofill, daytime urinary frequency, nocturia episodes per night, and Likert scale symptom scores were reviewed. Wilcoxon signed-rank tests, Wilcoxon rank-sum tests, Spearman's rank correlations, COX regression analysis, and a Kaplan-Meier survival curve were performed. RESULTS: Significant changes (median (25(th)-percentile to 75(th)-percentile) were noted for bladder capacity (75 mL (25 to 130 mL), p < 0.0001), inter-void interval (0 hrs (0 to 1 hour), p < 0.0001), nocturia episodes per night (-1 (-2 to 0), p < 0.0001), and aggregate Likert symptom scores (-2 points (-5 to 0), p < 0.0001). Percent change in bladder capacity correlated positively with percent change in inter-void interval (p = 0.03) and negatively with percent changes in nocturia (p = 0.17) and symptom scores (p = 0.01). Women without detrusor overactivity (DO) had greater percent changes in capacity than women with DO (62.5 % vs. 16.5 %, p = 0.02). 61.3 % of patients were retreated with a 36 weeks median time to retreatment and no difference in time to retreatment based upon DO. Greater capacity was protective against retreatment (hazard ratio = 0.997 [95 % CI 0.994,0.999], p = 0.02). CONCLUSIONS: Percent change in bladder capacity is a useful objective measure of response to intravesical DMSO/triamcinolone for newly diagnosed BPS/IC. Clinical outcomes do not differ based upon presence of DO.

Transforming growth factor ß 1 gene expression during vaginal vs cutaneous surgical woundexpression during vaginal vs cutaneous surgical wound healing in the rabbit.

INTRODUCTION AND HYPOTHESIS: Reconstructive pelvic surgery outcome is closely related to the vaginal and pelvic wound healing processes. Transforming growth factor beta 1 (TGF-ß1) is a principal mediator of wound repair in dermal tissue. We sought to assess this factor's expression in vaginal and dermal surgical wound repair in the rabbit. METHODS: We excised bilateral 6-mm full-thickness circular segments from the abdominal skin and vagina in 36 New Zealand White (NZW) nulliparous female rabbits. Animals were sacrificed before, on the day of, and 4, 7, 10, 14, 21, 28, and 35 days after tissue wounding, and their wounds were assessed for surface area and TGF-ß1 gene transcription by real-time polymerase chain reaction (PCR). RESULTS: In both the abdominal skin and vagina, TGF-ß1 gene transcription increased immediately after tissue injury, reaching maximal levels on days 4-7, and decreased shortly thereafter, attaining minimal values on day 35. A significant correlation between TGF-ß1 expression and the wound's closure rate was found in both tissues. CONCLUSIONS: TGF-ß1 gene transcription significantly correlates with the surgical vaginal and dermal wound closure rate, implying that this factor is involved in the process of wound repair in both tissues.

The PISQ-IR: considerations in scale scoring and development.

INTRODUCTION: This paper provides a detailed discussion of the psychometric analysis and scoring of a revised measure of sexual function in women with pelvic floor disorders (PFD): the Pelvic Organ Prolapse Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR). METHODS: Standard tools for evaluating item distributions, relationships, and psychometric properties were used to identify sub-scales and determine how the sub-scales should be scored. The evaluation of items included a nonresponse analysis, the nature of missingness, and imputation methods. The minimum number of items required to be answered and three different scoring methods were evaluated: simple summation, mean calculation, and transformed summation. RESULTS: Item nonresponse levels are low in women who are sexually active and the psychometric properties of the scales are robust. Moderate levels of item nonresponse are present for women who are not sexually active, which presents some concerns relative to the robustness of the scales. Single imputation for missing items is not advisable and multiple imputation methods, while plausible, are not recommended owing to the complexity of their application in clinical research. The sub-scales can be scored using either mean calculation or transformed summation. Calculation of a summary score is not recommended. CONCLUSION: The PISQ-IR demonstrates strong psychometric properties in women who are sexually active and acceptable properties in those who are not sexually active. To score the PISQ-IR sub-scales, half of the items must be answered, imputation is not recommended, and either mean calculation or transformed sum methods are recommended. A summary score should not be calculated.

Efficacy and safety of oxybutynin chloride topical gel for women with overactive bladder syndrome.

OBJECTIVE: This subgroup analysis of a phase-3 study evaluated the efficacy and safety of oxybutynin chloride topical gel (OTG) in women with overactive bladder syndrome (OAB). STUDY DESIGN: Women (n = 704) with urgency-predominant urinary incontinence received OTG or placebo for 12 weeks. The primary endpoint was change from baseline to last observation in number of daily incontinence episodes. Treatments were compared with the use of analysis of covariance. RESULTS: OTG significantly reduced the number (mean ± standard deviation) of daily incontinence episodes (OTG, -3.0 ± 2.8 episodes; placebo, -2.5 ± 3.0 episodes; P < .0001), reduced urinary frequency (P = .0013), increased voided volume (P = .0006), and improved select health-related quality-of-life domains (P ≤ .0161) vs placebo. Dry mouth was the only drug-related adverse event significantly more common with OTG (7.4%) than with placebo (2.8%; P = .0062). CONCLUSION: OTG was well tolerated and provided significant improvement in urinary symptoms and health-related quality of life in women with OAB.

Enhanced interpretability of the PFDI-20 with establishment of reference scores among women in the general population.

AIMS: To enhance the interpretability of the PFDI-20 by establishing a score distribution for women in the general population and to determine whether scores correspond with urinary and anal incontinence (UI and AI). METHODS: Subjects recruited during Twins Day Festivals from 2004 to 2009 completed a survey assessing for stress and urgency urinary incontinence (SUI and UUI) and AI of flatus and stool. Score distributions for the PFDI-20 and each of its subscales were determined for all subjects and for women with isolated forms of incontinence. Scores were compared between continent and incontinent women and between incontinent subtypes by Wilcoxon rank-sum tests. RESULTS: One thousand three hundred seventy-six women completed the survey with PFDI-20 (Median = 8.9, IQR 31.3), POPDI-6 (Median = 0, IQR = 8.3), CRADI-8 (Median = 0, IQR = 10.7), and UDI-6 (Median = 0, IQR = 16.7). PFDI-20, POPDI-6, CRADI-8, and UDI-6 scores were significantly greater among women reporting isolated SUI (P < 0.0001, P = 0.04, P < 0.0001, P < 0.0001, respectively), UUI (P < 0.0001, P = 0.02, P < 0.0001, P < 0.0001, respectively), mixed UI (P < 0.0001 each), AI flatus (P < 0.0001 each), and AI stool (P < 0.0001 each) compared to those denying incontinence. Women with mixed UI had significantly greater PFDI-20 and UDI-6 scores compare to those with SUI (P < 0.0001) or UUI (P < 0.0001). Subjects with AI stool had significantly greater PFDI-20 and CRADI-8 scores compared to those with AI flatus (P = 0.01). CONCLUSIONS: PFDI-20 scores from a sample of the general population correspond with the presence or absence of UI and AI. These normative and symptom-specific score distributions for the PFDI-20 provide reference points to gauge the effect of disease and intervention on quality of life for women with incontinence.

Can pelvic floor injury secondary to delivery be prevented?

The number of women suffering from pelvic floor disorders (PFD) is likely to grow significantly in the coming years with a growing older population. There is an urgent need to investigate factors contributing to the development of PFD and develop preventative strategies. We have reviewed the literature and analyzed results from our own study regarding the association between delivery mode, obstetrical practice and fetal measurements, and damage to the pelvic floor. Based on our findings, we have suggested a flowchart helping the obstetrician to conduct vaginal delivery with minimal pelvic floor insult. Primiparity, instrumental delivery, large fetal head circumference, and prolonged second stage of delivery are risk factors for PFD. Pelvic floor integrity should always be seriously considered in every primiparous woman. All efforts should be aimed at minimizing any insult, which might have a significant impact on the woman's pelvic integrity and future quality of life.

Vaginal incisional wound healing in a rabbit menopause model: a histologic analysis.

UNLABELLED: INTODUCTION AND HYPOTHESIS: The vaginal wound healing process is a major determinant of surgical outcome following pelvic reconstructive surgery. Since the majority of these surgeries are performed in peri- and postmenopausal women, it is essential to understand how estrogen deficiency affects this process. We aimed to histologically evaluate the vaginal incisional wound healing process in a rabbit menopause model. METHODS: Sixty three rabbits were utilized and divided into 3 groups: Twenty one underwent bilateral oophorectomy, 21 underwent a sham surgery, and 21 served as controls. Eight weeks later, standardized full-thickness 6 mm circular segments were excised from the vagina of all rabbits and spontaneous healing was recorded. Animals were euthanized sequentially, before wounding, and at 0, 4, 7, 14, 21 and 35 days after wounding, and their wounds were harvested and assessed histologically for wound healing using a validated scoring system. RESULTS: Oophorectomized rabbits showed significantly delayed wound closure (p < 0.02), neovascularization (p < 0.01), granulation tissue accumulation and maturation (p < 0.02), collagen deposition (p < 0.01) and re-epithelialization (p < 0.01), however acute and chronic inflammation were significantly enhanced (p < 0.02). CONCLUSION: Oophorectomized rabbits show protracted incisional vaginal wound healing by all histologic criteria, however, inflammation is significantly enhanced.

Trospium chloride once-daily extended release is efficacious and tolerated in elderly subjects (aged ≥ 75 years) with overactive bladder syndrome.

OBJECTIVE: • To evaluate the safety and efficacy of once-daily trospium chloride extended release (ER) in overactive bladder syndrome (OAB) in subjects aged ≥ 75 years. SUBJECTS AND METHODS: • The analysis included subjects ≥ 75 years of age with OAB. • A subgroup analysis of pooled data was performed for subjects aged ≥ 75 years from two randomized, double-blind, multicenter studies of subjects with OAB receiving once-daily trospium 60 mg extended release (ER) or placebo for 12 weeks, followed by 9-month open-label extension periods during which all subjects received trospium ER. A total of 143 of the 1165 subjects from two phase III registration trials who were aged ≥ 75 years (85 trospium ER, 58 placebo; mean age 79 years and ranging up to 90 years; 73% female) were evaluated. • Dual primary efficacy variables were the changes from baseline in the average number of toilet voids per day and urge urinary incontinence episodes per day. RESULTS: • At week 12 of the double-blind period, trospium ER produced greater improvements from baseline than placebo in voiding diary parameters, OAB Patient Global Assessment, and quality of life. • Efficacy and tolerability persisted among subjects receiving open-label trospium ER for up to 1 year. CONCLUSIONS: • Once-daily trospium chloride 60 mg ER demonstrated efficacy vs placebo and was tolerated in subjects aged ≥ 75 years with OAB. • For subjects who continued into the open-label treatment period, efficacy and tolerability were observed for up to 1 year.

Once-daily trospium chloride 60 mg extended-release provides effective, long-term relief of overactive bladder syndrome symptoms.

AIMS: Once-daily extended-release (XR) trospium chloride has been evaluated for the treatment of overactive bladder syndrome (OAB) in two 12-week randomized, double-blind, placebo-controlled studies. This pooled analysis of the 9-month open-label extensions to these studies evaluated the long-term efficacy and tolerability of trospium XR. METHODS: Following double-blind treatment, subjects with OAB could enter the open-label period, during which they received trospium 60 mg XR once daily for 36 weeks. The primary efficacy variables were changes from baseline in the number of toilet voids and urgency urinary incontinence (UUI) episodes per day at Week 48. Adverse events (AEs) were also recorded. RESULTS: Of the 1,027 subjects who completed double-blind treatment, 944 (92%) continued into the open-label period (placebo-to-trospium, N = 483; trospium-to-trospium, N = 461); 332 (68.7%) and 335 (72.7%), respectively, completed the open-label period. At Week 48, the mean change from baseline in the number of toilet voids/day was -3.21 in the placebo-to-trospium group and -3.35 in the trospium-to-trospium group, and the median change from baseline in the number of UUI episodes/day was -2.33 in both groups. Efficacy was maintained relative to Week 12 in trospium-to-trospium subjects, while improvement was seen following trospium initiation in placebo-to-trospium subjects. Improvement from baseline was also observed on secondary efficacy parameters at Week 48. Trospium was well tolerated; dry mouth and constipation were the most common class treatment-emergent AEs. Central nervous system AEs were rare and did not increase with long-term treatment. CONCLUSIONS: Long-term treatment of OAB with once-daily trospium 60 mg XR is effective and well tolerated.

An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint terminology and classification of the complications related directly to the insertion of prostheses (meshes, implants, tapes) and grafts in female pelvic floor surgery.

INTRODUCTION AND HYPOTHESIS: A terminology and standardized classification has yet to be developed for those complications arising directly from the insertion of synthetic (prostheses) and biological (grafts) materials in female pelvic floor surgery. METHODS: This report on the above terminology and classification combines the input of members of the Standardization and Terminology Committees of two International Organizations, the International Urogynecological Association (IUGA) and the International Continence Society (ICS) and a Joint IUGA/ICS Working Group on Complications Terminology, assisted at intervals by many expert external referees. An extensive process of 11 rounds of internal and external review took place with exhaustive examination of each aspect of the terminology and classification. Decision-making was by collective opinion (consensus). RESULTS: A terminology and classification of complications related directly to the insertion of prostheses and grafts in female pelvic floor surgery has been developed, with the classification based on category (C), time (T) and site (S) classes and divisions, that should encompass all conceivable scenarios for describing insertion complications and healing abnormalities. The CTS code for each complication, involving three (or four) letters and three numerals, is likely to be very suitable for any surgical audit or registry, particularly one that is procedure-specific. Users of the classification have been assisted by case examples, colour charts and online aids (www.icsoffice.org/complication). CONCLUSION: A consensus-based terminology and classification report for prosthesis and grafts complications in female pelvic floor surgery has been produced, aimed at being a significant aid to clinical practice and research.