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OBJECTIVE: The primary objective was to estimate the incidence of de novo stress urinary incontinence after total vaginal mesh procedures in women with negative preoperative urodynamics with prolapse reduction. Secondary objective was to identify associated risk factors. STUDY DESIGN: A retrospective cohort study with a nested case-control study of women who underwent total vaginal mesh procedures without midurethral sling after a negative preoperative urodynamics. RESULT: Sixty patients were included in the final analysis. Fifteen (25%) patients were diagnosed with de novo stress urinary incontinence. Although no significant associated risk factors were identified, there was a trend for higher gravidity and better anterior wall support among women who had stress urinary incontinence develop. CONCLUSION: The incidence of de novo stress urinary incontinence after total vaginal mesh procedures in this cohort was 25%. Patients should be appropriately counseled regarding the same. [ABSTRACT FROM AUTHOR]

Importance: Approximately 15-45% of female patients develop transient postoperative urinary retention (POUR) following pelvic reconstructive surgery. Catheter options for bladder drainage include transurethral indwelling catheter (TIC), intermittent self-catheterization (ISC), and suprapubic tube (SPT). Each strategy has risks and benefits; none have been shown to be clinically superior, and to date, no comprehensive comparative economic analysis has been published., Objective: The objective of this study was to evaluate the cost of these different bladder catheterization strategies after transvaginal pelvic surgery., Study Design: A Canadian universal single-payer (government funded) health system perspective was taken, and a decision tree model was constructed to evaluate the costs associated with each catheterization strategy over a 6-week horizon. Base-cases were set based on recently published clinical data of our institutions, 2 academic tertiary care centers, and based on systematic reviews and meta-analyses. Costs were established in consultation with process stakeholders, in addition to published values., Results: The average cost calculated for management of transient POUR after outpatient pelvic reconstructive surgery was 150.69 CAD (median 154.86; interquartile range [IQR] 131.30-176.33) for TIC, 162.28 CAD (median 164.72; IQR 144.36-189.39) for ISC and 255.67 CAD (median 270.63; IQR 234.32-276.82) for SPT. In costing inpatient surgical data, the average cost calculated was 134.22 CAD (median 123.61; IQR 108.87-151.85) for TIC and 224.61 CAD (median 216.07; IQR 203.86-231.23) for SPT., Conclusion: TIC and ISC were found to be significantly less costly than SPT in managing transient POUR following transvaginal pelvic reconstructive surgery., Competing Interests: Dr. Colleen McDermott is a medical advisor for Szio Inc., COSM Inc., Abbvie, and Lupin Pharma, and a speaker for Pfizer. These corporations were not involved in or influenced any facet of this study, including project development, data collection, and manuscript writing. The authors have declared they have no conflicts of interest., (Copyright © 2024 American Urogynecologic Society. All rights reserved.)

Objective: The objective of this study was to reduce the incidence of urinary tract infection (UTI) in women undergoing outpatient cystoscopy and/or urodynamic studies (UDS) at our centre by identifying and then altering modifiable risk factors through an analysis of incidence variability among physicians., Methods: This was a quality improvement study involving adult women undergoing outpatient cystoscopy and/or UDS at an academic tertiary urogynecology practice. Prophylactic practices for cystoscopy/UDS were surveyed and division and physician-specific UTI rates following cystoscopy/UDS were established. In consultation with key stakeholders, this delineated change concepts based on associations between prophylactic practices and UTI incidence, which were then implemented while monitoring counterbalance measures., Results: Two "Plan-Do-Study-Act-Cycles" were conducted whereby 212 and 210 women were recruited, respectively. Change concepts developed and implemented were: (1) to perform routine urine cultures at the time of these outpatient procedures, and (2) to withhold routine prophylactic antibiotics for outpatient cystoscopy/UDS, except in patients with signs of cystitis. There was no change in the incidence of early presenting UTI (9.0% vs. 9.2%, p = 0.680), but there were significantly fewer antibiotic-related adverse events reported (8.5% vs. 1.5%, p = 0.001). There was no significant change in the total incidence of UTI rates between cycles (7.8% vs. 5.6%, p = 0.649)., Conclusions: No specific strategies to decrease the incidence of UTI following outpatient cystoscopy/UDS were identified, however, risk factor-specific antibiotic prophylaxis, as opposed to universal antibiotic prophylaxis, did not increase UTI incidence., (© 2024 Wiley Periodicals LLC.)

Background: The distension properties of the vagina are critical to its function including support of surrounding organs, childbirth, and intercourse. It could be altered by many pathophysiological processes like pregnancy, radiotherapy, and reconstruction surgery. However, there are no clinically available diagnostic tools capable of quantifying the distension properties of the vagina., Purpose: A proof-of-concept study was designed to assess the feasibility of a novel three-dimensional (3D) ultrasound imaging technique that allows quantitative evaluation of the vagina under distension., Methods: Patients with symptomatic pelvic organ prolapse (POP) were recruited for the study. An ultrathin, oversized bag was inserted into the vagina and filled with water using a modified urodynamics system. The instilled water volume and intravaginal pressure were continuously recorded. At maximum vaginal capacity, 3D transintroital ultrasound of the distended vagina and surrounding pelvic structures was performed. Exams were performed in duplicate for each patient, two hours apart (round A and round B). Following the development of a 3D surface model of the distended vagina from each scan, several measurements were obtained, including cross-sectional area, anteroposterior (AP) length and lateral width in the plane of minimum hiatal dimensions (PMHD), AP and lateral diameter at the pubic symphysis (PS) level, maximum and minimum diameter, and maximum vertical length. To assess repeatability between measurements in two rounds, the coefficient of variation (CV) and the intraclass correlation coefficient (ICC) were calculated for each measurement. Correlations between physical measurements including the pelvic organ prolapse quantification (POP-Q) system and vaginal diameter measurements, and obtained metrics were also assessed., Results: Sixteen patients with POP (average age 69 years) completed both rounds of imaging. There was sufficient echogenicity on 3D transintroital ultrasound of the distended vaginal wall to establish boundaries for 3D surface models of the vagina. Overall, all metrics had good or excellent reliability (ICC = 0.77-0.93, p < 0.05; CV = 3%-18%) except maximum diameter, which demonstrated only moderate reliability (ICC = 0.67, p = 0.092). Strong correlations were found between physical exam measurements including D point of POP-Q, introitus diameter and lateral diameter at apex, and maximum vaginal capacity, maximum vertical length, lateral diameter at PS, minimum diameter, and distended PMHD measurements. The results demonstrated that this system could generate 3D models of the shape of the distended vagina and provide multiple metrics that could be reliably calculated from automated analyses of the models., Conclusions: A novel system for evaluation of the distension properties of the vagina was developed and preliminary evaluation was performed. This system may represent a technique for evaluation of the biomechanical and structural properties of the vagina., (© 2023 American Association of Physicists in Medicine.)

Importance: Vaginal pessaries are an effective nonsurgical treatment for pelvic organ prolapse (POP) when properly fitted. However, pessary fitting and use are often unsuccessful or imperfect., Objective: The objective of this study was to assess the feasibility of using patient-specific pessaries fabricated from three-dimensional (3D)-printed molds to improve POP symptoms and increase overall satisfaction of pessary treatment in patients using standard vaginal pessaries., Study Design: Patients undergoing POP treatment with standard vaginal pessaries were enrolled in this pilot prospective study. Patient-specific pessaries were designed and fabricated for each patient using patient input, physician input, and anatomic measurements from clinical assessment. Pessary fabrication involved injection of biocompatible liquid silicone rubber into 3D-printed molds followed by a biocompatible silicone coating. Pelvic organ prolapse symptomatic distress and pessary treatment satisfaction were evaluated before and after a 3-week patient-specific pessary home trial using the validated Pelvic Organ Prolapse Distress Inventory-6 form and a visual analog scale, respectively., Results: Eight women were included in this study. Changing from standard pessary to patient-specific pessary treatment was associated with an improvement in prolapse symptoms on the Pelvic Organ Prolapse Distress Inventory-6 (median change, -3.5; interquartile range, -5 to -2.5; P = 0.02) and an increase in overall pessary satisfaction on a visual analog scale (median change, +2.0; interquartile range, +1.0 to +3.0; P = 0.02). All patients reported either an improvement or no change in pessary ease of use, comfort, and the feeling of support provided by the pessary., Conclusion: Patient-specific vaginal pessaries are a promising alternative to standard pessaries for alleviating POP symptoms and improving patient satisfaction with pessary use., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To compare preoperative vitamin B2 versus intraoperative cystoscopy distension using 5% dextrose in water (D5W) for ureteric jet visualisation during pelvic reconstructive surgery., Design: Double-blinded, randomised controlled trial., Setting: Three tertiary hospitals in Toronto, Canada., Population: Adult women undergoing pelvic reconstructive surgery., Methods: Patients were randomised to receive 100 mg of vitamin B2 preoperatively versus bladder distension with D5W intraoperatively., Main Outcomes: The primary outcome was the rate of accurate detection of bilateral ureteric jets during cystoscopy. Secondary outcomes included the time elapsed until visualisation, use of intravenous furosemide or fluorescein to assist with visualisation, surgeon satisfaction, and positive urine culture 1 week after surgery., Results: The intervention was completed by 236 patients (vitamin B2 n = 117, D5W n = 119). Preoperative characteristics were similar across groups. Accurate detection of both ureteric jets was high in both groups (vitamin B2 97.4% vs. D5W 90.8%, p = 0.051). The vitamin B2 group had significantly lower use of fluorescein rescue compared with the D5W group (3.4% vs. 11.8%, respectively, p = 0.025). Surgeon satisfaction while using vitamin B2 was significantly higher (p < 0.001). There were no significant differences in the time elapsed until visualisation, the use of furosemide, or the incidence of positive urine culture at 1 week after surgery., Conclusions: Both preoperative vitamin B2 and intraoperative cystoscopy distension with D5W are highly available and inexpensive methods to detect ureteric jets with high accuracy at the time of pelvic reconstructive surgery. Vitamin B2 was shown to have lower rates of fluorescein rescue for visualisation and higher rates of surgeon satisfaction., (© 2022 John Wiley & Sons Ltd.)

Abstract: This clinical consensus statement on the management of postoperative (<6 weeks) urinary retention (POUR) reflects statements drafted by content experts from the American Urogynecologic Society's POUR writing group. The writing group used a modified Delphi process to evaluate statements developed from a structured literature search and assessed for consensus. After the definition of POUR was established, a total of 37 statements were assessed in the following 6 categories: (1) incidence of POUR, (2) medications, (3) patient factors, (4) surgical factors, (5) urodynamic testing, and (6) voiding trials. Of the 37 original statements, 34 reached consensus and 3 were omitted., Competing Interests: C.D.M. is a medical advisor for Szio, Inc, and COSM, Inc, and a speaker for Pfizer. These companies were not involved in any facet of this study. O.F.D.-G. is a consultant of Applied Medical and received a research grant from Merck, a biopharmaceutical company. These companies and organizations were not involved in any facet of this study. K.M. received royalties for Elsevier Publishing for book editing and is a consultant for RBI Medical, an executive board member of the Society of Gynecologic Surgeons (travel reimbursement), a nonpaid researcher for Cook MyoSure and Caldera Medical, and an editorial board member for the journals of Obstetrics and Gynecology and Urogynecology. These companies and organizations were not involved in any facet of this study. E.R.M. received an honorarium from UpToDate and research funding from the NIH, does legal consultation for Ethicon/Butler Snow, and is part of the research advisory board of Ferring. These companies were not involved in any facet of this study. The other authors have declared they have no conflicts of interest., (Copyright © 2023 American Urogynecologic Society. All rights reserved.)

Introduction and Hypothesis: Ehlers-Danlos Syndrome (EDS) is a group of inherited connective tissue disorders associated with abnormal collagen, and is more prevalent in women than in men. The aim of this cross-sectional study was to characterize pelvic floor symptoms in cisgender women with EDS and to describe their impact on quality of life., Methods: An online questionnaire on obstetric and gynecological experiences of cisgender women with EDS was disseminated through EDS patient societies and social media. This study was a sub-analysis of the broader questionnaire and focused on pelvic floor disorders, whereby self-reported symptoms and validated questionnaires were used to assess pelvic floor symptom severity (Pelvic Floor Distress Inventory, PFDI-20), impact on quality of life (Pelvic Floor Impact Questionnaire, PFIQ-7), and sexual function (Female Sexual Function Index, FSFI-6). Groups based on age and EDS type were compared using Kruskal-Wallis and Chi-squared tests., Results: A total of 1,303 participants were included in the analysis. Pelvic floor symptom prevalence included: stress urinary incontinence in 60%, urgency urinary incontinence in 54%, fecal incontinence in 24%, and pelvic organ prolapse in 21%. Bladder symptoms were reported to be the most bothersome. The impact of prolapse symptoms on quality of life was higher in women under age 40 than in older participants (p<0.001). Pelvic pain was reported in 71%. Pain ratings were highest for dysmenorrhea, muscle and joint pain, and backache (median 7 out of 10 for each). Almost half of participants screened positive for possible sexual dysfunction and 36% reported dyspareunia more than half the time., Conclusions: This large, observational study demonstrated that cisgender women with EDS report a high prevalence of pelvic floor symptoms that appear to be more severe than in the general population., (© 2022. The International Urogynecological Association.)

Objective: To determine the perioperative characteristics associated with an increased risk of postoperative urinary retention (POUR) following vaginal pelvic floor surgery., Design: A retrospective cohort study using multivariable prediction modelling., Setting: A tertiary referral urogynaecology unit., Population: Patients undergoing vaginal pelvic floor surgery from January 2015 to February 2020., Methods: Eighteen variables (24 parameters) were compared between those with and without POUR and then included as potential predictors in statistical models to predict POUR. The final model was chosen as the model with the largest concordance index (c-index) from internal cross-validation. This was then externally validated using a separate data set (n = 94) from another surgical centre., Main Outcome Measure: Diagnosis of POUR following surgery while the patient was in hospital., Results: Among the 700 women undergoing surgery, 301 (43%) experienced POUR. Preoperative variables with statistically significant univariate relationships with POUR included age, menopausal status, prolapse stage and uroflowmetry parameters. Significant perioperative factors included estimated blood loss, volume of intravenous fluid administered, operative time, length of stay and specific procedures, including vaginal hysterectomy with intraperitoneal vault suspension, anterior colporrhaphy, posterior colporrhaphy and colpocleisis. The lasso logistic regression model had the best combination of internally cross-validated c-index (0.73, 95% CI 0.71-0.74) and a calibration curve that showed good alignment between observed and predicted risks. Using this data, a POUR risk calculator was developed (https://pourrisk.shinyapps.io/POUR/)., Conclusions: This POUR risk calculator will allow physicians to counsel patients preoperatively on their risk of developing POUR after vaginal pelvic surgery and help focus discussion around potential management options., (© 2022 John Wiley & Sons Ltd.)

Objectives: The objective of the study was to determine practice patterns of prescribing prophylactic antibiotics against urinary tract infection (UTI) for urodynamic studies (UDS) and outpatient cystoscopy in women., Design: A cross-sectional survey study was conducted of North American female pelvic medicine and reconstructive specialists (FPMRS)., Methods: An online survey was used to assess prophylactic prescribing patterns of FPMRS that perform UDS and outpatient cystoscopy. This survey was developed and then electronically disseminated through the American Urogynecologic Society to 699 eligible physicians., Results: A total of 138 surveys were completed. Approximately half of physicians did not prescribe any antibiotic prophylaxis for UDS or for cystoscopy (54% and 43%, respectively). For patients with perceived risk factors (recurrent UTIs, immunosuppression, known neurogenic lower urinary tract dysfunction, indwelling catheter use, elevated postvoid residual/bladder outlet obstruction, genitourinary anomalies, and diabetes), 32% and 41% of physicians prescribed antibiotic prophylaxis for UDS and cystoscopy, respectively. A minority of physicians always prescribed antibiotics for UDS and cystoscopy (13% and 17%, respectively)., Limitations: The response rate was a limitation of the study; however, this rate is in keeping with other physician survey studies published within this subspecialty. Selection and response biases may have contributed to the results of this survey study., Conclusion: There was no uniform approach to UTI prophylaxis for UDS and outpatient cystoscopy in women which reflects the lack of current guidelines and the low level of evidence on which they are based. This nonuniform practice calls for more research to better define an evidence-based standard of care., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Objectives: To determine the real-world effectiveness of pelvic floor muscle therapy (PFMT) recommendations for patients., Methods: We conducted a cross-sectional study of 70 women who were advised to undergo PFMT after their initial urogynaecology consultation for lower urinary tract symptoms and/or pelvic organ prolapse. About half (51%) of potential participants consented to answer our telephone survey. We calculated the proportion of patients who complied with the recommendation of PFMT, and we subjectively assessed whether these patients found PFMT to be helpful. We also collected demographic data and looked for reasons why patients did not attend PFMT. Chi-square, 2-tailed t, or Fisher exact tests were used to compare differences between patients who attended and those who did not., Results: During the 6-month period after their initial consultation, only 28 of 70 women (40%) followed the recommendation to attend PFMT. Sixteen of the 28 women who attended PFMT (57%) reported that they found it helpful. Therefore, the "real-world effectiveness" of the entire study sample was 23%, with only 16 of 70 women benefiting from PFMT. Time constraints (27%) and cost (18%) were the top 2 reasons given for not attending., Conclusions: Despite evidence-based recommendations in favour of PFMT for various pelvic floor disorders, its real-world effectiveness is quite low. A public health commitment to providing access to PFMT would be of significant benefit., (Copyright © 2021 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to determine nursing preferences regarding catheter type (transurethral indwelling catheters vs intermittent catheterization vs suprapubic tube drainage) when caring for patients in hospital after pelvic organ prolapse surgery., Design: Cross-sectional survey study., Subjects and Setting: Registered nurses practicing in academic and community hospitals across North America (the United States and Canada)., Methods: Three hundred fifty-four RNs who routinely care for patients after pelvic organ prolapse surgery from centers across North America were sent an electronic survey between February 2018 and March 2019. The survey comprised 24 questions that collected information on the participants' demographics and their experience with using different catheters in a hospital setting, along with knowledge of and preference for the different catheter types. Descriptive statistics were used to determine catheter preferences of respondents in addition to their catheter rankings according to catheter-related outcomes., Results: One hundred sixty nurses completed the survey, representing a 45% response rate. More than half (63.1%, n = 101) of respondents stated a preference for transurethral indwelling catheters, 23.1% (n = 37) preferred suprapubic tubes, and 10.6% (n = 17) preferred intermittent catheterization. Transurethral indwelling catheters were ranked by nurses as the best catheter type for ease of use and pain/discomfort for patients. Intermittent catheterization was ranked by nurses as the best for lowest malfunction rates and return of bladder function. Suprapubic tubes were ranked by nurses as best for lowest infection rates., Conclusions: This study has demonstrated that nurses practicing in inpatient care units have a strong preference for transurethral indwelling catheters over intermittent catheterization and suprapubic tubes when caring for patients after pelvic organ prolapse surgery., Competing Interests: Dr Colleen McDermott is a medical advisor for Szio Inc and COSM Inc. Neither was involved in any facet of this study including project development, data collection, and manuscript writing. No other financial disclaimer or potential conflicts of interest relating to this project to disclose., (Copyright © 2021 by the Wound, Ostomy and Continence Nurses Society.)

Introduction and Hypothesis: To describe study design flaws and limited outcomes of a randomized trial that intended to compare satisfaction and complication rates between patients managing their pelvic organ prolapse with a pessary at different maintenance intervals., Methods: A randomized clinical trial was conducted at two tertiary pessary clinics. After a successful fitting, patients were randomly allocated to follow-up at 3-month or 6-month intervals and followed for 12 months. Symptoms, complications, and pelvic examination characteristics were recorded at each visit. At 6 and 12 months, patient satisfaction with the pessary was also recorded. Sample size calculation was based on the minimal relevant difference in Pessary Satisfaction score (created for this study). With a power of 0.8 and an alpha of 0.05, the minimum number of patients required in each group was 28., Results: We were unable to reach our sample size as most patients did not meet inclusion criteria. After 2 years we were only able to recruit 20/56 patients, with 9 patients in the 3-month group and 11 patients in the 6-month group. Additionally, seven patients dropped out of the study. Overall satisfaction was high and similar between groups at 6- and 12-month follow-up visits. Pessary complications were noted in both groups but in low numbers., Conclusions: Pessary use is associated with high patient satisfaction and low complication rates, regardless of the follow-up interval. The recruitment failure demonstrated that a randomized trial is not feasible for this research question. Optimally, pessary follow-up should be based on patient symptoms and scheduling preference.

Objective: The aim of this study was to determine surgeon preference for catheter type in the management of postoperative urinary retention after prolapse surgery, specifically comparing transurethral indwelling catheters (TIC), clean intermittent self-catheterization (CISC), and suprapubic tubes (SPT)., Methods: Electronic surveys were sent to 1182 urogynecologists and urologists through the American Urogynecologic Society and the Canadian Society of Pelvic Medicine., Results: A total of 247 (21%) surveys were completed, where 53% of the respondents ranked TIC as the best catheter option, compared with 42% for CISC and 4% for SPT (P < 0.0001). Most (75%) of the respondents stated they do not offer their patients a choice in catheter selection. Most (43%) of the respondents ranked ease of use for the patient as the most important catheter characteristic. For ease of use for the patient, 71% of the respondents ranked TIC as the best, compared with CISC and SPT. For all other characteristics (pain/discomfort, infection, catheter malfunction, and return of bladder function), CISC was ranked as the best by the majority., Conclusions: This study showed that surgeons have a significant preference for TIC over CISC and SPT for the management of postoperative urinary retention, and the majority of surgeons do not offer their patients a choice with regard to catheter type., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2019 American Urogynecologic Society. All rights reserved.)

Introduction and Hypothesis: Urinary tract infection is the most common complication after urodynamic studies (UDS). Practice guidelines recommend against antibiotic prophylaxis based on an outdated review of the literature, which advised on the premise of "a lack of good quality studies" and based on an assumed low incidence not consistently supported by the literature., Objectives: This systematic review aims to update the assessment of the efficacy of antibiotic prophylaxis compared with placebo or no treatment for prevention of urinary tract infection in females over the age of 18 years undergoing UDS., Methods: MEDLINE, EMBASE, COCHRANE, DISSERTATIONS, conference proceedings and clinical trial registries were searched for relevant randomized controlled trials. Two authors independently screened and selected articles, assessed these for quality according to Cochrane guidelines and extracted their data., Results: A total of 2633 records were screened, identifying three relevant randomized controlled trials. The one study that was critically appraised as being the least likely biased showed a statistically significant effect of antibiotic prophylaxis in reducing bacteriuria post UDS in female patients. The other two studies included in the review did not. None of the studies included were powered to show a significant change in the incidence of urinary tract infection following UDS in female patients receiving antibiotic prophylaxis versus no prophylaxis., Conclusions: Similar to the 2012 Cochrane review on this subject, this systematic review demonstrated that antibiotic prophylaxis may decrease bacteriuria in women post UDS; however, further research is required to assess its effect on urinary tract infections in this context.

There are limited data on the management of pregnancy and delivery after midurethral sling (MUS) surgery for stress urinary incontinence (SUI). We report a case of a 39-year-old woman who underwent an MUS in July 2017. She reported a 10-year history of frequency, urgency with rare urge incontinence, nocturia, and occasional SUI when coughing or sneezing. Preoperative assessment did not include a pregnancy test. Two days after MUS placement, she developed complete urinary retention, and it was determined that she was 6 weeks pregnant. She was referred to a tertiary urogynecology unit and was seen at 23 weeks' gestation with worsening symptoms of urinary frequency and nocturia. She also described difficulty voiding but no incontinence. She was managed with conservative measures initially, but by 35 weeks, she required intermittent self-catherization (ISC). She underwent an elective cesarean delivery at 39 weeks' gestation. She reported postvoid dribbling, urge incontinence, and recurrent SUI at 10 months postpartum. This case report adds to the body of knowledge around outcomes of MUS during and after pregnancy.

Introduction and Hypothesis: Although some psychiatric anxiety questionnaires include overactive bladder (OAB) questions, there are few controlled data to confirm such an association. We tested the association between OAB and anxiety using a control group of women with non-OAB lower urinary tract symptoms (LUTS)., Methods: Patients referred to a urogynecology clinic for LUTS completed two questionnaires: the International Consultation on Incontinence Modular Questionnaire for Overactive Bladder (ICIQ-OAB), and the Generalized Anxiety Disorder 7-Item Scale (GAD-7). Based on ICIQ-OAB scores, patients were dichotomized as having OAB versus LUTS-other, and GAD-7 scores categorized patients as having anxiety. A 2-tailed Fisher's exact test was used to test the association between OAB and anxiety. Demographic variables were collected and significant confounders were included in a logistic regression analysis. Sample size calculation indicated a need for 100 subjects, but we recruited 105 subjects to account for incomplete questionnaires., Results: One hundred and five subjects were enrolled (one excluded owing to incomplete questionnaires). Sixty-five patients had OAB and 39 had LUTS-other. Of the OAB patients, 17 out of 65 (26.2%) had anxiety, compared with 3 out of 39 (7.7%) of the LUTS-other group (p = 0.038 by Fisher's exact test, with a slight drop to p = 0.056 in the regression analysis)., Conclusions: There appears to be an association between OAB and anxiety and it may be of clinical importance to assess for anxiety in patients that present with OAB symptoms. The drop in statistical significance from p = 0.038 to a borderline significance of p = 0.056 in the regression analysis may be a reflection of the sample size.

Introduction and Hypothesis: Pre-emptive gabapentin has been shown to decrease postoperative pain in abdominal and vaginal hysterectomy. However, the effect of pre-emptive low-dose gabapentin has not been studied in vaginal hysterectomy combined with concomitant pelvic reconstruction., Methods: A randomized double-blind placebo-controlled trial assessed all women seen for symptomatic prolapse requiring vaginal hysterectomy with concomitant pelvic reconstruction with or without midurethral sling. Gabapentin dosing was 600 mg (<65 years) or 300 mg (>65 years). The primary outcome was reduction in opioid consumption in the first 24 h after surgery. Secondary outcomes included sedation and prolongation of recovery room stay. Sample-size calculations indicated a need for 22 participants/group. Student's t test was used to compare differences in oral administration of morphine equivalents in the first 24 h postoperatively, time from end of surgery to leaving the recovery room, and length of recovery room stay. Mann-Whitney U test was used to compare visual analog scale (VAS) scores for anxiety, drowsiness/sedation, pain, and nausea., Results: Twenty-one patients received gabapentin and 26 a placebo capsule. Groups were similar with respect to age, menopause status, parity, American Society of Anesthesiologist (ASA) class, and concomitant procedures. There were also no significant differences between groups in opioid requirements within the first 24 h after surgery, time from end of surgery to leaving the recovery room, length of time in recovery room, or VAS scores., Conclusions: Pre-emptive gabapentin at our institutional low doses did not significantly affect postoperative pain and opioid requirements in women undergoing vaginal hysterectomy with concomitant reconstruction., Trial Registration: www.clinicaltrials.gov , #NCT02999724.

Objective: The objective of this study was to perform a cost-utility analysis of nonsurgical treatments for stress urinary incontinence (SUI) in healthy adult women with a health system perspective over a 1-year time horizon., Methods: A decision tree model was constructed to evaluate the following nonsurgical treatment options for SUI in a simulated healthy adult female cohort who had failed Kegel exercises: pelvic floor muscle therapy (PFMT), a disposable tampon device (Impressa), a self-fitting intravaginal incontinence device (Uresta), and a traditional incontinence pessary. Published data and consultation with health care providers were used to estimate efficacies and costs. Health utility estimates were derived from existing literature. Deterministic sensitivity analyses were performed as well as Monte Carlo probabilistic sensitivity analysis to account for the impact of parameter uncertainty on costs and efficacies for each treatment. Our primary outcome was the highest net monetary benefit (NMB), which represents the monetary value of the health benefits less the treatment costs. The standard willingness-to-pay threshold of US $50,000 per quality-adjusted life year was used., Results: The utility of SUI in an otherwise healthy patient was 0.81 ± 0.16 and for subjective cure was 0.93 ± 0.08. Using base-case estimates, PFMT was the most cost-effective treatment with an NMB of US $44,098. The Impressa tampon, Uresta, and traditional pessary had NMBs of US $43,970, $43,785, and $42,846, respectively. The probabilistic sensitivity analysis confirmed PFMT to be the most cost-effective treatment option at a willingness to pay of US $50,000 per quality-adjusted life year., Conclusions: The findings of our cost-utility analysis favor PFMT as the most cost-effective nonsurgical treatment option for SUI. Cost-effectiveness for 1 year of treatment was also favorable for Impressa and Uresta. In jurisdictions where there is no public funding for PFMT, Impressa or Uresta are alternatives for women wishing to avoid surgery.

Objectives: Bladder drainage can be achieved by clean intermittent self-catheterization (CISC), transurethral indwelling catheterization (TIC), or with a suprapubic tube (SPT). The primary objective of this study was to determine patient preference for catheter type in the management of potential voiding dysfunction after pelvic organ prolapse (POP) surgery., Methods: Between 2012 and 2016, patients scheduled for POP surgery were recruited into the study. Before surgery, patients were informed of the potential for postoperative voiding dysfunction and the catheter choices were discussed. Each patient's choice was recorded along with baseline information, surgery performed, and perioperative details. After surgery, voiding dysfunction, length of catheter use, scores on a catheter satisfaction questionnaire, as well as uroflowmetry and urine culture testing were assessed., Results: Of those recruited to the study (N = 150), 6.7% chose CISC, 7.3% chose TIC, and 86% chose SPT. Catheter satisfaction score 1 week after surgery was significantly better for SPT compared with CISC and TIC (P = 0.005). In addition, at week 1, 33% of CISC, 25% of TIC, and 13% of SPT had a PVR of more than 30% (P = 0.002) on uroflowmetry, and 33% of CISC, 50% of TIC, and 24% of SPT had a positive urine culture (P = 0.05)., Conclusions: This study has shown that patients prefer SPT over CISC and TIC for management of voiding dysfunction after POP surgery. Use of SPT showed better satisfaction rates, better uroflowmetry results, and lower infection rates 1 week after surgery. Patient preference is an important factor in this decision and can help facilitate a clinical approach.

Objective: The aim of this study was to assess the current status of female pelvic medicine and reconstructive surgery (FPMRS) in Canada, including level of training, practice patterns, barriers to practice and opinions among obstetrician-gynecologists (OB/GYNs) and urologists., Methods: Electronic surveys were distributed to 737 OB/GYNs through the Society of Obstetricians and Gynaecologists of Canada and to 489 urologists through the Canadian Urological Association., Results: Complete responses were collected from 301 (41%) OB/GYNs and 39 (8%) urologists. Of the OB/GYN respondents, 57% were generalists (GEN), and 22% completed FPMRS fellowship training (FPMRS-GYN). OB/GYN GENs were less likely than FPMRS-GYNs to report comfort with pelvic organ prolapse quantification assessment, urodynamic testing, cystoscopy, treatment of mesh complications, and management of overactive bladder. Urologists were less likely than FPMRS-GYNs to report comfort completing a pelvic organ prolapse quantification assessment, fitting pessaries, and treating mesh complications but more likely to report comfort managing overactive bladder. FPMRS-GYNs were more likely than other providers to report high volumes (>20 cases in the past year) of vaginal hysterectomy, as well as incontinence and prolapse procedures. OB/GYN GENs and urologists frequently cited lack of formal training in residency as a barrier to performing FPMRS procedures, whereas FPMRS-GYNs reported a lack of operating room facilities and support personnel. Overall, 76% of the respondents were of the opinion that FPMRS should be a credentialed Canadian subspecialty (92% FPMRS-GYN, 69% OB/GYN GEN, 59% urologists)., Conclusions: OB/GYN GENs reported low case volumes and cited inadequate training in residency as a barrier to surgically managing pelvic floor disorders. Most respondents felt that FPMRS should be a credentialed subspecialty.

Background: Residency programs struggle with integrating simulation training into curricula, despite evidence that simulation leads to improved operating room performance and patient outcomes. Currently, there is no standardized laparoscopic training program available for gynecology residents., Objective: The purpose of this study was to develop and validate a comprehensive ex vivo training curriculum for gynecologic laparoscopy., Study Design: In a prospective, single-blinded randomized controlled trial (Canadian Task Force Classification I) postgraduate year 1 and 2 gynecology residents were allocated randomly to receive either conventional residency training or an evidence-based laparoscopy curriculum. The 7-week curriculum consisted of cognitive didactic and interactive sessions, low-fidelity box trainer and high-fidelity virtual reality simulator technical skills, and high-fidelity team simulation. The primary outcome measure was the technical procedure score at laparoscopic salpingectomy with the use of the objective structured assessment of laparoscopic salpingectomy tool. Secondary outcome measures related to performance in multiple-choice questions and technical performance at box trainer and virtual reality simulator tasks. A sample size of 10 residents per group was planned (n = 20). Results are reported as medians (interquartile ranges), and data were compared between groups with the Mann-Whitney U, chi-square, and Fisher's exact tests (P ≤ .05)., Results: In July 2013, 27 residents were assigned randomly (14 curriculum, 13 conventional). Both groups were similar at baseline. Twenty-one residents (10 curriculum, 11 conventional) completed the surgical procedure-based assessment in the operating room (September to December 2013). Our primary outcome indicated that curriculum-trained residents displayed superior performance at laparoscopic salpingectomy (P = .043). Secondary outcomes demonstrated that curriculum-trained residents had higher performance scores on the cognitive multiple-choice questions (P < .001), the nontechnical skills multiple-choice questions (P = .016), box trainer task time (P < .001), and all virtual reality simulator parameters., Conclusion: Participation in a comprehensive simulation-based training curriculum for gynecologic laparoscopy leads to a superior improvement in knowledge and technical performance in the operating room compared with conventional residency training., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The probiotic yeast Saccharomyces boulardii has been shown to ameliorate disease severity in the context of many infectious and inflammatory conditions. However, use of S. boulardii as a prophylactic agent or therapeutic delivery vector would require delivery of S. boulardii to a healthy, uninflamed intestine. In contrast to inflamed mucosal tissue, the diverse microbiota, intact epithelial barrier, and fewer inflammatory immune cells within the healthy intestine may all limit the degree to which S. boulardii contacts and influences the host mucosal immune system. Understanding the nature of these interactions is crucial for application of S. boulardii as a prophylactic agent or therapeutic delivery vehicle. In this study, we explore both intrinsic and immunomodulatory properties of S. boulardii in the healthy mucosal immune system. Genomic sequencing and morphological analysis of S. boulardii reveals changes in cell wall components compared to non-probiotic S. cerevisiae that may partially account for probiotic functions of S. boulardii. Flow cytometry and immunohistochemistry demonstrate limited S. boulardii association with murine Peyer's patches. We also show that although S. boulardii induces a systemic humoral immune response, this response is small in magnitude and not directed against S. boulardii itself. RNA-seq of the draining mesenteric lymph nodes indicates that even repeated administration of S. boulardii induces few transcriptional changes in the healthy intestine. Together these data strongly suggest that interaction between S. boulardii and the mucosal immune system in the healthy intestine is limited, with important implications for future work examining S. boulardii as a prophylactic agent and therapeutic delivery vehicle.

Unlabelled: Beyond the well-defined role of the Eph (erythropoietin-producing hepatocellular) receptor tyrosine kinases in developmental processes, cell motility, cell trafficking/adhesion, and cancer, nothing is known about their involvement in liver pathologies. During blood-stage rodent malaria infection we have found that EphB2 transcripts and proteins were up-regulated in the liver, a result likely driven by elevated surface expression on immune cells including macrophages. This was significant for malaria pathogenesis because EphB2(-/-) mice were protected from malaria-induced liver fibrosis despite having a similar liver parasite burden compared with littermate control mice. This protection was correlated with a defect in the inflammatory potential of hepatocytes from EphB2(-/-) mice resulting in a reduction in adhesion molecules, chemokine/chemokine receptor RNA levels, and infiltration of leukocytes including macrophages/Kupffer cells, which mediate liver fibrosis during rodent malaria infections. These observations are recapitulated in the well-established carbon tetrachloride model of liver fibrosis in which EphB2(-/-) carbon tetrachloride-treated mice showed a significant reduction of liver fibrosis compared to carbon tetrachloride-treated littermate mice. Depletion of macrophages by clodronate-liposomes abrogates liver EphB2 messenger RNA and protein up-regulation and fibrosis in malaria-infected mice., Conclusion: During rodent malaria, EphB2 expression promotes malaria-associated liver fibrosis; to our knowledge, our data are the first to implicate the EphB family of receptor tyrosine kinases in liver fibrosis or in the pathogenesis of malaria infection., (© 2015 by the American Association for the Study of Liver Diseases.)

Objective: To examine outcomes after primary obstetric anal sphincter injuries in a subsequent pregnancy., Methods: This was a retrospective analysis of prospectively collated data from a large perinatal database between 2006 and 2010. Primiparous vaginal deliveries with an obstetric anal sphincter injury were identified and tracked to identify their subsequent delivery characteristics and perineal outcomes., Results: A primary obstetric anal sphincter injury occurred in 5.3% of primiparous vaginal deliveries (9,857/186,239); of those patients, 2,093 had a subsequent delivery, and 91.9% delivered vaginally (1,923/2,093). The recurrent obstetric anal sphincter injury rate was also found to be 5.3% (102/1,923). The adjusted odds ratios (ORs) for primary obstetric anal sphincter injuries were significantly increased in large-for-gestational-age neonates for both third-degree laceration (adjusted OR 2.1, 95% confidence interval [CI] 1.9-2.2) and fourth-degree laceration (adjusted OR 2.7, 95% CI 2.3-3.1) and almost all obstetric interventions studied. The adjusted ORs for recurrent obstetric anal sphincter injuries were significant for large-for-gestational-age (25/102, adjusted OR 2.2, 95% CI 1.3-3.6) and instrumental deliveries (15/102, adjusted OR 2.4, 95% CI 1.2-4.6)., Conclusion: In this study population, the incidence of recurrent obstetric anal sphincter injuries was similar to that of primary obstetric anal sphincter injuries, and most patients went on to deliver vaginally for subsequent deliveries. The risk of recurrent obstetric anal sphincter injuries was doubled in those who delivered a large-for-gestational-age neonate and in those who had an instrumental delivery.

Recent studies have suggested the potential of probiotic organisms to be adapted for the synthesis and delivery of oral therapeutics. The probiotic yeast Saccharomyces boulardii would be especially well suited for this purpose due to its ability, in contrast to probiotic prokaryotes, to perform eukaryotic post translational modifications. This probiotic yeast thus has the potential to express a broad array of therapeutic proteins. Currently, however, use of wild type (WT) S. boulardii relies on antibiotic resistance for the selection of transformed yeast. Here we report the creation of auxotrophic mutant strains of S. boulardii that can be selected without antibiotics and demonstrate that these yeast can express functional recombinant protein even when recovered from gastrointestinal immune tissues in mice. A UV mutagenesis approach was employed to generate three uracil auxotrophic S. boulardii mutants that show a low rate of reversion to wild type growth. These mutants can express recombinant protein and are resistant in vitro to low pH, bile acid salts, and anaerobic conditions. Critically, oral gavage experiments using C57BL/6 mice demonstrate that mutant S. boulardii survive and are taken up into gastrointestinal immune tissues on a similar level as WT S. boulardii. Mutant yeast recovered from gastrointestinal immune tissues furthermore retain expression of functional recombinant protein. These data show that auxotrophic mutant S. boulardii can safely express recombinant protein without antibiotic selection and can deliver recombinant protein to gastrointestinal immune tissues. These auxotrophic mutants of S. boulardii pave the way for future experiments to test the ability of S. boulardii to deliver therapeutics and mediate protection against gastrointestinal disorders.

Objectives: Obesity can predispose women to pelvic organ prolapse and can also affect the success of pelvic organ prolapse surgery. The purpose of this study was to compare the postoperative anatomical outcomes following sacral colpopexy (SC) and transvaginal mesh colpopexy in a group of obese women with pelvic organ prolapse., Methods: We conducted a retrospective cohort study of obese women who underwent SC (n = 56) or transvaginal mesh colpopexy (n = 35). Follow-up ranged from 6 to 12 months. Preoperative, perioperative, and postoperative variables were compared using Student t, Mann-Whitney U, and Fisher exact tests, and by analysis of covariance., Results: The women in the SC group had significantly higher mean apical vaginal measurements (P < 0.05), and significantly fewer stage II recurrences than women in the transvaginal mesh colpopexy group. There were no significant differences between the groups for other postoperative outcomes, including mesh erosion, recurrent prolapse symptoms, dyspareunia, and surgical satisfaction (P > 0.05)., Conclusion: In these 91 obese patients with pelvic organ prolapse, SC resulted in better anatomical outcomes than transvaginal mesh colpopexy. However, the two procedures had similar outcomes with regard to recurrent symptoms and surgical satisfaction.

Background: Obesity is a risk factor for female pelvic floor disorders. The study objective was to determine whether there was a difference in the subjective reporting of pelvic symptoms before and after bariatric surgery., Methods: This was a prospective cohort study of female patients that underwent bariatric surgery. Patients completed a demographic questionnaire, the Pelvic Floor Distress Inventory-20 (PFDI-20), and the Pelvic Floor Impact Questionnaire-7 (PFIQ-7) before surgery and at 6 and 12 months following surgery. Body mass index (BMI) was compared between time points using Student's t tests (P < 0.05 significant). Symptom and impact on quality of life prevalence were compared using McNemar's test and questionnaire scores were compared using the Wilcoxon matched pairs test (P < 0.025 significant)., Results: At 12 months after surgery, 63 patients had completed the study. Even with significant weight loss (BMI, 43.7 kg/m(2) to BMI, 29 kg/m(2); P < 0.001), there was no significant difference in the prevalence of pelvic floor symptoms before and after surgery (94% to 81%, P = 0.2). Prevalence of pelvic floor symptom impact on quality of life did significantly decrease after surgery (56% to 30%; P = 0.004). Baseline PFDI-20 and PFIQ-7 scores were low; however, there was still a significant reduction in PFDI-20 and PFIQ-7 scores after surgery (P < 0.001)., Conclusions: Prevalence of pelvic floor symptoms did not vary greatly after surgery; however, significant weight reduction did improve the degree of bother and quality of life related to these symptoms.

Introduction and Hypothesis: The aim of this study was to determine the reoperation rate for sling placement or revision in patients who had primary continence procedures based on prolapse reduction stress testing (RST) prior to laparoscopic sacral colpoperineopexy (LSCP)., Methods: This was a retrospective cohort study of women who had RST prior to LSCP for symptomatic pelvic organ prolapse. Patients with positive test (Pos RST) had a concomitant midurethral sling procedure and those with negative test (Neg RST) did not. Variables were compared with either Student's t test or Fisher's exact test., Results: In Neg RST group (n = 70), the rate of surgery for de novo urodynamic stress incontinence was 18.6%. In Pos RST group (n = 82), the rate of sling revision for bladder outlet obstruction was 7.3%. Overall, 88% of patients did not require a second surgery., Conclusions: The use of RST to recommend concomitant continence procedures during LSCP results in a single surgery for the majority of our patients.

Objective: Obesity can predispose women to pelvic organ prolapse and can also affect the success of prolapse surgery. Sacral colpopexy is a common surgical approach used to treat significant prolapse, and may be performed by laparotomy or laparoscopy. The objective of this study was to determine whether surgical outcomes following abdominal sacral colpopexy (ASC) and laparoscopic sacral colpopexy (LSC) varied according to BMI., Methods: We conducted a retrospective cohort study of women who had undergone ASC (n = 90) and LSC (n = 150). Preoperative, perioperative, and postoperative information was collected from patient charts and entered into a database according to BMI category (normal weight 18.5 to 24.9 kg/m², overweight = 25 to 29.9 kg/m², obese ≥ 30 kg/m²). Within each BMI group, outcomes were compared between ASC and LSC patients using Student t, Mann-Whitney U, and Fisher exact tests, and analyses of covariance., Results: In normal weight patients, postoperative apical measurements were worse in ASC patients (P = 0.01). In overweight patients, the ASC group had worse posterior measurements (P = 0.05) and fewer mesh/suture erosions (P = 0.03) but more recurrent prolapse symptoms (P = 0.007). In obese patients, the ASC group had better anterior measurements (P = 0.008). There were no differences in any BMI category for prolapse stage, surgical satisfaction, or classification of surgical success or failure (P > 0.05)., Conclusion: Differences between ASC and LSC were identified when patients were categorized according to BMI. These findings may be useful in counselling patients and planning the appropriate surgical approach for sacral colpopexy based on BMI.

Purpose: The occurrence of stress urinary incontinence and pelvic organ prolapse can often coexist resulting in the need for concomitant surgical procedures to treat both conditions. The purpose of this study was to determine if tension-free vaginal tape (TVT) at the time of laparoscopic sacral colpoperineopexy (LSCP) had an effect on distal anterior vaginal wall support., Methods: This was a retrospective cohort study of patients that had LSCP between January 2005 and December 2007 (n = 121). These patients were divided according to those with (n = 63) and without TVT (n = 58) at the time of LSCP. Pre- and postoperative information was compared between groups using Student's t tests, ANCOVA, and Fisher's exact tests (P ≤ 0.05)., Results: Preoperatively, there were no significant differences between groups for all demographic and anatomic variables (P > 0.05). Patients were followed-up until 12 months after surgery. Patients with and without TVT had similar postoperative anterior vaginal wall measurements (points Aa and Ba) and stage of prolapse (P > 0.05). There were also no differences between groups with regard to recurrent prolapse symptoms or surgical satisfaction (P > 0.05)., Conclusions: Tension-free vaginal tape at the time of LSCP did not improve postoperative distal anterior vaginal support.

Introduction and Hypothesis: Laparoscopic sacral colpoperineopexy (LSCP) involves posterior graft extension to the perineum for improved posterior support. The objective of this study was to determine whether posterior measurements differed between those that had graft extension done abdominally (A-LSCP) or abdomino-vaginally (AV-LSCP)., Methods: This was a retrospective cohort study of patients that underwent A-LSCP (n = 17) and AV-LSCP (n = 51). Pre-, peri-, and postoperative variables were compared using Student's t, Fisher's exact, and analysis of covariance tests., Results: Follow-up was 6 to 12 months. There were no differences between A-LSCP and AV-LSCP for any vaginal measurements or stage of prolapse (P > 0.05). Although not statistically different, A-LSCP patients had lower rates of mesh erosion and dyspareunia (P > 0.05). AV-LSCP patients had fewer prolapse symptoms (P = 0.01), but both groups had similar surgical satisfaction (P= 0.8)., Conclusions: A-LSCP and AV-LSCP had comparable effects on posterior vaginal measurements; however, mesh erosion and subjective outcomes differed between the two approaches.

Background: Total Prolift(®) is a pelvic floor repair system that is performed transvaginally and can be carried out with or without the uterus in situ., Aim: To compare surgical outcomes following total Prolift colpopexy (TPC) and total Prolift hysteropexy (TPH)., Methods: This was a retrospective cohort study of women that underwent TPC (n = 65) or TPH (n = 24). Outcomes were compared between groups using Student's t-test, ANCOVA and Fisher's exact tests (P ≤ 0.05)., Results: There were no significant differences between TPC and TPH for all peri-operative variables. Patients were followed 6-12 months after surgery. Post-operatively, TPC patients had significantly higher pelvic organ prolapse-quantification (POP-Q) point C measurements (P = 0.05); however, all other POP-Q measurements were similar, including POP-Q apical stage of prolapse, with 99% in the TPC group and 92% in the TPH group at stage I or less. Post-operative mesh erosion, prolapse symptoms, surgical satisfaction, sexual activity and dyspareunia rates did not significantly differ between groups., Conclusions: This study showed that TPC and TPH have similar surgical outcomes, except for vaginal vault measurements reflected by POP-Q point C., (© 2011 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology © 2011 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Objectives: : Pelvic organ prolapse (POP) and stress urinary incontinence often require concomitant procedures to treat both conditions. The purpose of this study was to determine whether tension-free vaginal tape (TVT) at the time of total Prolift colpopexy (TPC) affected distal anterior vaginal wall support., Methods: : This was a retrospective cohort study of women that had TPC (n = 62) between January 2005 and December 2007. All patients had no uterus and underwent TPC with mesh placement in the anterior and posterior vaginal compartments. A concomitant TVT was placed only in those who had a preoperative diagnosis of urodynamic stress urinary incontinence with prolapse reduction. Patients were subdivided into those with (n = 26) and without TVT (n = 36). Data were compared between groups using Student t, Wilcoxon rank sum, and Fisher exact tests (P ≤ 0.05)., Results: : There were no significant differences between groups for all preoperative variables. Patients were observed for 6 to 12 months after TPC. Postoperatively, those with and without TVT had similar anterior POP quantification measurements (points Aa and Ba; P > 0.05), although the group with TVT had significantly more patients with anterior stage 2 and 3 recurrences (23%) when compared with the group without TVT (5%, P = 0.04)., Conclusions: : Tension-free vaginal tape does not provide additional distal anterior vaginal wall support for patients undergoing TPC.

Objective: to determine the effectiveness of universal versus targeted screening for hepatitis C (HCV) during pregnancy at an urban health care centre., Methods: we conducted a cross-sectional study of 653 pregnant women. Patients completed a demographic and standardized questionnaire identifying known risk factors for HCV. Patients then underwent blood testing for HCV antibodies. The effectiveness of screening based on risk factors was determined by comparing the number of women who screened positive for HCV risk factors with those who tested seropositive., Results: of those who entered the study, 0.5% (3/645) tested positive for HCV. HCV risk factor screening showed that 72% answered "Yes" to one or more risk factors and 28% answered "No" to all risk factors. Answering "Yes" to any risk factor was not associated with testing positive for HCV antibodies (P > 0.05). Screening positive for a high severity risk factor (exposure to intravenous drug use or to the blood of an HCV-positive individual) was associated with testing positive for HCV antibodies (P = 0.002), but screening positive for a moderate or low severity risk factor was not (P > 0.05)., Conclusion: during pregnancy, universal testing for HCV and testing based on the presence of any risk factors for HCV is not recommended. HCV testing based on the presence of high severity risk factors, however, may be warranted.

Abdominal correction of pelvic organ prolapse remains a viable option for patients and surgeons. The transition from open procedures to less invasive laparoscopic and robotic-assisted surgeries is evident in the literature. This article reviews the surgical options available for pelvic organ prolapse repair and their reported outcomes. Procedures reviewed include apical support (sacral, uterosacral, and others), and abdominal anterior and posterior vaginal wall support. Long-term follow-up and appropriately designed studies will further help direct surgeons in deciding which approach to incorporate into their practice.

Purpose: To study the activity of the novel anti-angiogenic compound AG3340 (Prinomastat), a selective inhibitor of matrix metalloproteases, in an animal model of retinal neovascularization., Methods: C57BL/6J mice were used to produce oxygen-induced retinal neovascularization. Mice were exposed to room air from birth (P0) to postnatal 7 days (P7) and to hyperoxia (75% oxygen) for the next 5 days. On postnatal day 12 (P12) the animals were returned to the room air and were treated until postnatal day 16 (P16) with intraperitoneal injections of AG 3340. Four groups were assigned: no drug, 1.6 mg/kg/day, 16 mg/kg/day and 48 mg/kg/day. On day 17 (P17) the animals were sacrificed and the eyes prepared for histological sectioning. Preretinal neovascularization was assessed by counting neovascular nuclei of endothelial cells in the preretinal side of the internal limiting membrane (ILM). The use of animals for this study complies with the ARVO guidelines for animal research., Results: AG3340 administered systemically by intraperitoneal injections inhibited hypoxia-induced retinal neovascularization. The inhibition was dose dependent with highly significant decrease of neovascular nuclei counts among eyes treated with 0, 1.6 mg/kg, 16 mg/kg and 48 mg/kg doses. There appears to be a saturation effect of inhibition at the level of 70% at the two highest doses of 16 mg/kg and 48 mg/kg., Conclusions: AG3340 administered systemically significantly inhibits oxygen-induced retinal neovascularization in an animal model and appears to be a promising candidate for the treatment of neovascular retinal diseases.

To determine the ocular pharmacokinetics, physiological and histological effects of prinomastat (a matrix metalloprotease inhibitor), a total of seventy-seven eyes of New Zealand White rabbits received intravitreous and subtenon injections of prinomastat or of acidified water vehicle as control, Doses of 0.5 mg in 0.05 mL of prinomastat or acidified water were used for intravitreal injection. For the subtenon injections, doses of 5 mg prinomastat in 0.5 mL of acidified water were administered in the superotemporal quadrant. Intraocular pharmacokinetics were determined by analyzing vitreous samples at different postinjection time points using Liquid Chromatography-Mass Spectroscopy/Mass Spectroscopy (LC-MS/MS). The toxicity was evaluated by biomicroscopy, electroretinography (ERG), pneumatonometry, and histology. No toxicity was found with either administration method. At day 14 after intravitreal injection, levels of prinomastat in the vitreous and choroid were 1.4 ng/mg and 7.8 ng/mg, respectively. The retinal levels of prinomastat were 22 ng/mg at 24 hr and dropped below 1 ng/mg at 48 hr. Prinomastat remained well above minimum effective concentration in the choroid for at least four weeks after a single intravitreal injection, suggesting that local intravitreal injection may have potential in treating choroidal neovascularization.

Purpose: To determine the efficacy of prinomastat (AG3340), a synthetic inhibitor of matrix metalloproteinase, in the treatment of experimental proliferative vitreoretinopathy (PVR) induced by intravitreal dispase injection., Methods: One eye each of 53 New Zealand white rabbits was injected in the vitreous cavity with 0.07 unit of dispase to induce PVR. One week after PVR induction, 53 rabbits were randomized (27:26) to receive 0.5 mg prinomastat or the vehicle of the drug (acidified water) intravitreally every two weeks. The scores of PVR severity (scale of 1-5) were graded to compare the prinomastat-treated animals with the control group., Results: The average PVR scores in the treatment and control groups were 2.62 and 3.57 respectively (p = 0.038; Wilcoxon rank sum). Clinically significant PVR with retinal detachment (PVR > or = grade 3) developed in 76% of rabbits in the control group versus 51% of rabbits treated with prinomastat., Conclusions: Intravitreally administered prinomastat decreased development of PVR in an experimental model which made use of dispase to induce PVR.

Effective therapy is needed to improve the survival of patients with advanced lung cancers. We studied the effects of a selective metalloprotease inhibitor, AG3340, on chemoresistant human non-small cell lung cancer tumors (line MV522) in vivo. Mice bearing s.c. tumors were given twice-daily oral doses of AG3340. As a single agent, AG3340 inhibited angiogenesis (up to 77%) and tumor growth (up to 65%) in a dose-dependent manner at well-tolerated daily doses up to 400 mg/kg/day and induced significant tumor necrosis. In contrast, tumors were relatively insensitive to carboplatin with approximately 25% growth inhibition observed at a maximum tolerated dose of approximately 30 mg/kg/week (given i.p., twice weekly). Carboplatin inhibited tumor growth markedly only at toxic doses, demonstrating a superior therapeutic index of AG3340 to carboplatin in this tumor model. A suboptimal dose of AG3340, when used in combination with an ineffective maximum tolerated dose of carboplatin, resulted in greater tumor growth inhibitions than those produced by either agent alone. Similarly, growth inhibition was enhanced when AG3340 was used in combination with paclitaxel. Cotreatment with carboplatin did not alter AG3340 plasma concentrations achieved acutely after oral dosing. These data demonstrate an antiangiogenic and antitumor effect of AG3340 when used as a single agent and enhanced growth inhibitions when AG3340 is used in combination with cytotoxic agents. These data suggest that treatment with this novel matrix metalloprotease inhibitor may be beneficial in advanced lung cancers and other chemoresistant malignancies.

We studied AG3340, a potent metalloproteinase (MMP) inhibitor with pM affinities for inhibiting gelatinases (MMP-2 and -9), MT-MMP-1 (MMP-14), and collagenase-3 (MMP-13) in many tumor models. AG3340 produced dose-dependent pharmacokinetics and was well tolerated after intraperitoneal (i.p.) and oral dosing in mice. Across human tumor models, AG3340 produced profound tumor growth delays when dosing began early or late after tumor implantation, although all established tumor types did not respond to AG3340. A dose-response relationship was explored in three models: COLO-320DM colon, MV522 lung, and MDA-MB-435 breast. Dose-dependent inhibitions of tumor growth (over 12.5-200 mg/kg given twice daily, b.i.d.) were observed in the colon and lung models; and in a third (breast), maximal inhibitions were produced by the lowest dose of AG3340 (50 mg/kg, b.i.d.) that was tested. In another model, AG3340 (100 mg/kg, once daily, i.p.) markedly inhibited U87 glioma growth and increased animal survival. AG3340 also inhibited tumor growth and increased the survival of nude mice bearing androgen-independent PC-3 prostatic tumors. In a sixth model, KKLS gastric, AG3340 did not inhibit tumor growth but potentiated the efficacy of Taxol. Importantly, AG3340 markedly decreased tumor angiogenesis (as assessed by CD-31 staining) and cell proliferation (as assessed by bromodeoxyuridine incorporation), and increased tumor necrosis and apoptosis (as assessed by hematoxylin and eosin and TUNEL staining). These effects were model dependent, but angiogenesis was commonly inhibited. AG3340 had a superior therapeutic index to the cytotoxic agents, carboplatin and Taxol, in the MV522 lung cancer model. In combination, AG3340 enhanced the efficacy of these cytotoxic agents without altering drug tolerance. Additionally, AG3340 decreased the number of murine melanoma (B16-F10) lesions arising in the lung in an intravenous metastasis model when given in combination with carboplatin or Taxol. These studies directly support the use of AG3340 in front-line combination chemotherapy in ongoing clinical trials in patients with advanced malignancies of the lung and prostate.

Chronic rejection is one of the principal factors that lead to development of obliterative bronchiolitis, which is the cause of death for 50% of lung allograft recipients. To more fully comprehend the pathogenesis of chronic rejection, we investigated the expression of endothelin-1 (ET-1) and endothelin-converting enzyme-1 (ECE-1) in inadequately immuno-suppressed rat lung allografts (n = 15) at monthly intervals after transplantation and compared these findings with those in normal rat lung (n = 5), using immunohistochemistry. Throughout the posttransplantation period, inflammatory cells expressed weak to moderate immunoexpression for both peptides. Constant weak to moderate immunoexpression for both peptides was also seen in the alveolar epithelium and neovascularized endothelium. Early after transplantation the vascular endothelium demonstrated strong immunostaining compared with control sections. This immunostaining, however, was reduced to control levels at later stages of rejection. As rejection progressed, staining in the airway epithelium diminished to weak levels as compared with that in controls. These findings suggest a causal role for ET-1 and ECE-1 in the inflammatory and proliferative damage associated with chronic rejection after lung transplantation.

Matrix metalloproteinases are a family of zinc-containing proteases that degrade extracellular matrix and basement membranes. These enzymes are thought to play a role in processes essential for tumor growth, invasion, and metastasis. Here we report pharmacokinetic and anti-tumor efficacy studies with a series of structurally related inhibitors of these enzymes that were synthesized at Agouron Pharmaceuticals using protein structure based drug design. The compounds studied were AG3287, AG3293, AG3294, AG3296, AG3319, and AG3340. Rat oral bioavailability ranged from 15 to 68%. Despite similar profiles of enzyme inhibition across the family of enzymes, and similar pharmacokinetics following i.p. administration to mice, efficacy against the Lewis lung carcinoma murine model varied from tumor growth enhancement, to significant reductions in the size of primary tumors and the number of lung metastases. AG3340 was the most efficacious compound against the Lewis lung carcinoma model, resulting in the complete cessation of primary tumor growth throughout the experiment in 4/6 mice treated with daily i.p. injections at a dose of 50 mg/kg. This treatment inhibited the formation of lung metastases greater than 5 mm in diameter by 90%.

Background: Obliterative bronchiolitis (OB) is a disease affecting a large percentage of lung and heart-lung transplant recipients. Histologically, the disease is characterized by inflammation, cellular proliferation, and obliteration of terminal airways., Methods: We investigated the production of inducible and constitutive nitric oxide synthases and peroxynitrite by immunohistochemistry in the lungs of control subjects (n=14) compared with those of transplant recipients with OB (n=8)., Results: Strong immunoreactivity for inducible nitric oxide synthase and nitrotyrosine, a marker of protein nitration by peroxynitrite, was seen in inflammatory cells, airway epithelium, and vascular endothelium of patients with OB, compared with little immunoreactivity in control lungs. Immunoreactivity for constitutive nitric oxide synthase was abundant in the airway epithelium and vascular endothelium of control lungs, however, it was decreased in airway epithelial cells and arterial endothelial cells of patients with OB., Conclusions: We conclude that increased formation of the potent oxidant peroxynitrite and decreased production of endothelial nitric oxide may contribute to the functional and morphological abnormalities of OB.