Risk of pelvic organ prolapse treatment based on extended family history.

BACKGROUND: Family history of pelvic organ prolapse among first-degree relatives is an established risk factor for pelvic organ prolapse; however, consideration of the constellation of family history that extends to distant relationships allows for more accurate determination of risk and may improve pelvic organ prolapse risk prediction estimates. OBJECTIVE: The purpose of this study was to assess risk for pelvic organ prolapse treatment based on varying family histories of pelvic organ prolapse and included number and types of affected relatives, ages of relatives at pelvic organ prolapse treatment, and whether the family history is of maternal or paternal origin. STUDY DESIGN: This was a retrospective, population-based study that involved the Utah Population Database, which is a population resource that includes extensive genealogy information linked to medical records. The study population included 453,522 total women: 4628 women with a diagnosis of treated (surgical or pessary) pelvic organ prolapse and their 15,530 first-degree relatives; 33,782 second-degree relatives, and 66,469 third-degree relatives. We estimated relative risk of treated pelvic organ prolapse based on specific family history constellations. RESULTS: Relative risk estimates increased with a family history of increasing numbers of treated first-degree relatives with pelvic organ prolapse (first-degree relatives, ≥1 [relative risk, 2.36; 95% confidence interval, 2.15-2.58], first-degree relatives, ≥2 [relative risk, 3.79; 95% confidence interval, 2.65-5.24], and first-degree relatives, ≥3 [relative risk, 6.26; 95% confidence interval, 1.29-18.30]). Having a family history of ≥3 affected third-degree relatives (eg, first cousins) and no affected first- or second-degree relatives was similar in risk to having 1 affected first-degree relative. Relative risk estimates decreased with increasing age of treatment for first-degree family members. Risks in individuals with a positive maternal family history for pelvic organ prolapse were consistently higher than risks in individuals with equivalent paternal family history, but paternal inheritance still played a role. Approximately 4% of the total studied female population was found to have a >2-fold risk of being treated for pelvic organ prolapse and is considered high-risk based on their family history. CONCLUSION: We provide estimates for treated pelvic organ prolapse based on an extensive family history of pelvic organ prolapse using a large population-based sample. Risk for treated pelvic organ prolapse increased with increasing numbers of affected close and distant female relatives, earlier age of pelvic organ prolapse treatment in relatives, and maternal inheritance. These risk estimates may be useful for genetic studies and investigation of risk reduction strategies in those at highest risk for pelvic organ prolapse.

Models for Predicting Recurrence, Complications, and Health Status in Women After Pelvic Organ Prolapse Surgery.

OBJECTIVE: To develop statistical models predicting recurrent pelvic organ prolapse, surgical complications, and change in health status 12 months after apical prolapse surgery. METHODS: Logistic regression models were developed using a combined cohort from three randomized trials and two prospective cohort studies from 1,301 participants enrolled in surgical studies conducted by the Pelvic Floor Disorders Network. Composite recurrent prolapse was defined as prolapse beyond the hymen; the presence of bothersome bulge symptoms; or prolapse reoperation or retreatment within 12 months after surgery. Complications were defined as any serious adverse event or Dindo grade III complication within 12 months of surgery. Significant change in health status was defined as a minimum important change of SF-6D utility score (±0.035 points) from baseline. Thirty-two candidate risk factors were considered for each model and model accuracy was measured using concordance indices. All indices were internally validated using 1,000 bootstrap resamples to correct for bias. RESULTS: The models accurately predicted composite recurrent prolapse (concordance index=0.72, 95% CI 0.69-0.76), bothersome vaginal bulge (concordance index=0.73, 95% CI 0.68-0.77), prolapse beyond the hymen (concordance index=0.74, 95% CI 0.70-0.77), serious adverse event (concordance index=0.60, 95% CI 0.56-0.64), Dindo grade III or greater complication (concordance index=0.62, 95% CI 0.58-0.66), and health status improvement (concordance index=0.64, 95% CI 0.62-0.67) or worsening (concordance index=0.63, 95% CI 0.60-0.67). Calibration curves demonstrated all models were accurate through clinically useful predicted probabilities. CONCLUSION: These prediction models are able to provide accurate and discriminating estimates of prolapse recurrence, complications, and health status 12 months after prolapse surgery.

The cost of preoperative urodynamics: A secondary analysis of the ValUE trial.

AIMS: Urodynamic studies (UDS) are generally recommended prior to surgical treatment for stress urinary incontinence (SUI), despite insufficient evidence that it impacts treatment plans or outcomes in patients with uncomplicated SUI. This analysis aimed to calculate the cost incurred when UDS was performed as a supplement to a basic office evaluation and to extrapolate the potential savings of not doing UDS in this patient population on a national basis. METHODS: This is a secondary analysis from the Value of Urodynamic Evaluation (ValUE) trial, a multicenter non-inferiority randomized trial to determine whether a basic office evaluation (OE) is non-inferior in terms of SUI surgery outcomes to office evaluation with addition of urodynamic studies (UDS). All participants underwent an OE; those patients who randomized to supplementary UDS underwent non-instrumented uroflowmetry, filling cystometry, and a pressure flow study. Costs associated with UDS were calculated using 2014 U.S. Medicare allowable fees. Models using various patient populations and payor mixes were created to obtain a range of potential costs of performing UDS in patients undergoing SUI surgery annually in the United States. RESULTS: Six hundred thirty women were randomized to OE or OE plus UDS. There was no difference in surgical outcomes between the two groups. The per patient cost of UDS varied from site to site, and included complex cystometrogram $314-$343 (CPT codes 51728-51729) plus complex uroflowmetry $16 (CPT code 51741). Extrapolating these costs for US women similar to our study population, 13-33 million US dollars could be saved annually by not performing preoperative urodynamics. CONCLUSION: For women with uncomplicated SUI and a confirmatory preoperative basic office evaluation, tens of millions of dollars US could be saved annually by not performing urodynamic testing. In the management of such women, eliminating this preoperative test has a major economic benefit.

Evidence for pelvic organ prolapse predisposition genes on chromosomes 10 and 17.

OBJECTIVE: We conducted a genomewide linkage analysis to identify pelvic organ prolapse (POP) predisposition genes using a resource of high-risk POP pedigrees. STUDY DESIGN: Cases are defined as women who reported bothersome symptoms of POP based on standardized symptom questions (Pelvic Floor Distress Inventory, moderately or quite bothered), and/or received treatment for POP documented in medical records. Our complete pedigree resource contains 299 familial POP cases in 83 high-risk pedigrees. Genotype data were obtained from Illumina HumanHap550, 610Q, the Human1M-Duo, Human Omni1-Quad, or the Human Omni 2.5 platforms. A set of single nucleotide polymorphism markers common to all platforms was identified and markers in high linkage disequilibrium were removed. We performed a genomewide linkage analysis under general dominant and recessive models using a Markov chain, Monte Carlo linkage analysis method implemented in MCLINK (University of Utah) software. Because 70 individuals in 32 pedigrees were used in a previously published linkage analysis for a phenotype of POP requiring treatment/surgery, we also performed linkage only including the 225 newly recruited and genotyped cases in 61 pedigrees. RESULTS: Linkage analysis using our complete pedigree resource for the loosened criteria of bothersome POP showed evidence for significant genomewide linkage on chromosome 10q24-26 (recessive model, maximum heterogeneity logarithm of odds 3.4); suggestive evidence was identified on chromosomes 6 and 17, and an additional region on chromosome 10. In the subset of only the newly recruited familial POP cases, significant evidence for genomewide linkage was observed on chromosome 17q25 (recessive model, maximum heterogeneity logarithm of odds 3.3), and suggestive evidence for linkage was observed on chromosomes 10 and 11. Neither analysis duplicated the previously published linkage evidence for the POP requiring treatment/surgery phenotype observed on chromosome 9. CONCLUSION: While the etiology of this common condition is unknown, this study provides evidence that loci on chromosomes 10q and 17q may contribute to POP etiology.

Clinical characteristics of women with familial pelvic floor disorders.

INTRODUCTION AND HYPOTHESIS: Understanding the clustering of pelvic floor disorders (PFDs) within families is important because it may suggest underlying risk factors that may be environmental, genetic or both. The objective of this study was to describe clinical characteristics observed in familial cases with PFDs and compare them with strictly defined controls. METHODS: Women evaluated and treated for PFDs were recruited as part of a larger genetic study. Here, we define familial cases as those with bothersome symptoms or treatment for a PFD (pelvic organ prolapse [POP], stress urinary incontinence [SUI], and overactive bladder [OAB]) and who had a first-degree relative with bothersome symptoms or treatment for the same pelvic floor defect. We assigned clinical characteristics to probands and their relatives using standardized symptom questions (PFDI), examination, and review of treatment records, if any. RESULTS: We identified 126 familial POP cases, 183 familial SUI cases, and 101 familial OAB cases. Familial cases were more likely to have bothersome symptoms for more than one PFD. Among familial POP cases, bothersome SUI (71 %), OAB (54 %), and a combination of all three disorders (48 %) were common. Among familial SUI cases, bothersome OAB (60 %), POP (59 %), and combinations of all disorders (40 %) were common. Among familial OAB cases, bothersome SUI (88 %), POP (66 %), and combinations of all three disorders (59 %) were common. CONCLUSIONS: Familial cases of POP, SUI, and OAB are more likely to have more than one pelvic floor defect. It is likely that underlying genetic factors contribute to more than one pelvic floor defect.

Risk of associated conditions in relatives of subjects with interstitial cystitis.

OBJECTIVES: Urological chronic pelvic pain syndrome includes interstitial cystitis/painful bladder syndrome (IC/PBS), a chronic bladder pain condition of unknown etiology. Interstitial cystitis/painful bladder syndrome can co-occur with a number of associated conditions such as irritable bowel syndrome and fibromyalgia. The purpose of this study was to estimate the heritability of approximately 20 associated conditions in first-degree relatives (and if appropriate, second- and third-degree relatives) of patients with IC/PBS to identify shared genetic contributions for the disease combinations. METHODS: We used the Utah Population Database, a unique population-based genealogical database that has been linked to electronic health records for the University of Utah Health Sciences Center back in 1994. Interstitial cystitis/painful bladder syndrome probands were identified by the International Classification of Diseases, Ninth Revision code for chronic interstitial cystitis and had genealogy information for 12 of their 14 immediate ancestors. We calculated excess risk of an associated condition in relatives of patients with IC/PBS using relative risk estimates. RESULTS: We identified 248 IC/PBS probands. We found that 2 associated conditions, myalgia and myositis/unspecified (fibromyalgia) as well as constipation, were in significant excess in the patients with IC/PBS themselves, their first-degree relatives, and their second-degree relatives. The excess risk among relatives between IC/PBS and these associated conditions also held in the converse direction. Excess risk of IC/PBS was observed in the first- and second-degree relatives in probands with myalgia and myositis/unspecified (fibromyalgia) and in probands with constipation. CONCLUSIONS: These results suggest that myalgia and myositis/unspecified (fibromyalgia) as well as constipation are likely to share underlying genetic factors with IC/PBS.

Repeat post-op voiding trials: an inconvenient correlate with success.

AIMS: This study examined the association between the need for a repeat voiding trial after midurethral sling (MUS) surgery and 1-year success rates. METHODS: We conducted this secondary analysis of the participants in the Urinary Incontinence Treatment Network trial of midurethral sling (TOMUS) study which compared retropubic versus transobturator MUS. A standard voiding trial was attempted on all subjects. The "repeat voiding trial" group included subjects discharged with catheterization. All others were considered "self voiding." Success rates between the groups at 1-year were compared, followed by multivariate analyses controlling for previously reported clinical predictors of success. RESULTS: Most women (76%) were self-voiding, while 24% required a repeat voiding trial. The objective success rate at 1-year was 85.8% in the repeat voiding trial group and 75.3% in the self-voiding group (P = 0.01). Subjective success rate at 1-year was 61.0% in the repeat voiding trial group and 55.1% in the self-voiding group (P = 0.23). Women in the repeat voiding trial group continued to demonstrate greater objective success than the self-voiding group in multivariate analysis that controlled for previous incontinence surgery, pad weight, urethral mobility, urge score, and type of MUS (P = 0.04, OR 1.82, 95% CI 1.03-3.22). CONCLUSIONS: Women who require a repeat voiding trial following MUS surgery have greater objective success at 1-year postoperatively when compared to those who are self-voiding at the time of discharge. These results may help reassure women who require catheterization after MUS surgery that their outcome is not compromised by this immediate transient post-operative result.

Risk factors for incomplete bladder emptying after midurethral sling.

OBJECTIVE: To describe the prevalence and risk factors for incomplete bladder emptying after midurethral slings (MUS) in a large multicenter trial. METHODS: Five hundred ninety-seven women were randomized to retropubic (RMUS) or transobturator midurethral slings as part of the Trial of MidUrethral Slings study. Demographic data and voiding symptoms were obtained preoperatively along with urodynamics. Patients underwent a standardized voiding trial at discharge after continence surgery. Incomplete bladder emptying was defined as a postvoid residual of >150 mL. RESULTS: Three-quarters of patients (454 of 597) were self-voiding at discharge, whereas 114 of 597 (19%) were managed with an indwelling urethral catheter and 29 of 597 (5%) with intermittent catheterization. At 2 weeks, only 38 of 586 (6%) reported any catheter use, and by 6 weeks, only 9 of 587 (2%) reported any catheter use. Women with incomplete bladder emptying at discharge were more likely to have had a RMUS (odds ratio 1.79; 95% confidence interval 1.22-2.62) and to report preoperative voiding accommodations such as straining to void (odds ratio 1.75; 95% confidence interval 1.04-2.96). Urodynamic and clinicodemographic parameters were not predictive of incomplete bladder emptying. CONCLUSION: Incomplete bladder emptying at discharge after MUS is common, especially after RMUS, but of short duration. Risk factors include preoperative voiding accommodations such as straining or bending over to void, but other variables including urodynamics did not predict incomplete bladder emptying after MUS.

The familiality of pelvic organ prolapse in the Utah Population Database.

INTRODUCTION AND HYPOTHESIS: Pelvic organ prolapse (POP) in women is a common condition whose etiology is poorly understood. There is increasing evidence that POP is heritable. The aim of our study was to define and evaluate familial clustering of POP. METHODS: Using a population-based Utah genealogy linked to more than a decade of hospital data, we calculated relative risks (RR) of POP in female relatives of women with POP using age- and birth year-specific rates of POP. We compared the average pairwise relatedness of all POP cases to the population using a measure of genetic distance. RESULTS: We identified 1,292 women with diagnostic and procedure codes for POP. The RR of POP was significantly elevated in first- and third-degree female relatives (RR 4.15, p < 0.001; RR 1.24, p = 0.05). The average pairwise relatedness for all individuals with POP was significantly higher than expected (p < 0.001). CONCLUSIONS: These results strongly support a significant heritable contribution to POP.

Phenotyping clinical disorders: lessons learned from pelvic organ prolapse.

Genetic epidemiology, the study of genetic contributions to risk for disease, is an innovative area in medicine. Although research in this arena has advanced in other disciplines, few genetic epidemiological studies have been conducted in obstetrics and gynecology. It is crucial that we study the genetic susceptibility for issues in women's health because this information will shape the new frontier of personalized medicine. To date, preterm birth may be one of the best examples of genetic susceptibility in obstetrics and gynecology, but many areas are being evaluated including endometriosis, fibroids, polycystic ovarian syndrome, and pelvic floor disorders. An essential component to genetic epidemiological studies is to characterize, or phenotype, the disorder to identify genetic effects. Given the growing importance of genomics and genetic epidemiology, we discuss the importance of accurate phenotyping of clinical disorders and highlight critical considerations and opportunities in phenotyping, using pelvic organ prolapse as a clinical example.

A randomized trial of urodynamic testing before stress-incontinence surgery.

BACKGROUND: Urodynamic studies are commonly performed in women before surgery for stress urinary incontinence, but there is no good evidence that they improve outcomes. METHODS: We performed a multicenter, randomized, noninferiority trial involving women with uncomplicated, demonstrable stress urinary incontinence to compare outcomes after preoperative office evaluation and urodynamic tests or evaluation only. The primary outcome was treatment success at 12 months, defined as a reduction in the score on the Urogenital Distress Inventory of 70% or more and a response of "much better" or "very much better" on the Patient Global Impression of Improvement. The predetermined noninferiority margin was 11 percentage points. RESULTS: A total of 630 women were randomly assigned to undergo office evaluation with urodynamic tests or evaluation only (315 per group); the proportion in whom treatment was successful was 76.9% in the urodynamic-testing group versus 77.2% in the evaluation-only group (difference, -0.3 percentage points; 95% confidence interval, -7.5 to 6.9), which was consistent with noninferiority. There were no significant between-group differences in secondary measures of incontinence severity, quality of life, patient satisfaction, rates of positive provocative stress tests, voiding dysfunction, or adverse events. Women who underwent urodynamic tests were significantly less likely to receive a diagnosis of overactive bladder and more likely to receive a diagnosis of voiding-phase dysfunction, but these changes did not lead to significant between-group differences in treatment selection or outcomes. CONCLUSIONS: For women with uncomplicated, demonstrable stress urinary incontinence, preoperative office evaluation alone was not inferior to evaluation with urodynamic testing for outcomes at 1 year. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT00803959.).

Identification of six loci associated with pelvic organ prolapse using genome-wide association analysis.

OBJECTIVE: There is evidence that both environmental and genetic factors contribute to pelvic organ prolapse. We conducted a genome-wide association study to investigate whether common genetic variants modify the risk of pelvic organ prolapse. METHODS: We recruited women who had been evaluated and treated for pelvic organ prolapse at the University of Utah from 1996 to 2008 and their affected female relatives. Those in the case group were genotyped on the Illumina 550K platform. We genetically matched 2,976 white control participants available from Illumina as the control group. Association tests were adjusted for related participants using two different software programs: EMMAX and Genie. Confirmation of findings was performed in a cohort of Dutch women (n=76) with recurrent pelvic organ prolapse and family history of pelvic organ prolapse. RESULTS: The Utah study sample included 115 case group participants treated for pelvic organ prolapse, in most case group participants with surgery (n=78) or repeat surgery (n=35). Results from association analyses using EMMAX software identified five single-nucleotide polymorphisms (SNPs) significantly associated with pelvic organ prolapse (P<1×10). Independent association analysis with Genie software identified three of the same SNPs and one additional SNP. The six SNPs were located at 4q21 (rs1455311), 8q24 (rs1036819), 9q22 (rs430794), 15q11 (rs8027714), 20p13 (rs1810636), and 21q22 (rs2236479). Nominally significant findings (P<.05) or findings trending toward significance (P<.1) were observed for five of the six SNPs in the Dutch cohort. CONCLUSION: Six SNPs have been identified that are significantly associated with pelvic organ prolapse in high-risk familial case group participants and that provide evidence for a genetic contribution to pelvic organ prolapse. LEVEL OF EVIDENCE: II.

Adverse events over two years after retropubic or transobturator midurethral sling surgery: findings from the Trial of Midurethral Slings (TOMUS) study.

OBJECTIVE: To describe surgical complications in 597 women over a 24-month period after randomization to retropubic or transobturator midurethral slings. STUDY DESIGN: During the Trial of Midurethral Slings study, the Data Safety Monitoring Board regularly reviewed summary reports of all adverse events using the Dindo Surgical Complication Scale. Logistic regression models were created to explore associations between clinicodemographic factors and surgical complications. RESULTS: A total of 383 adverse events were observed among 253 of the 597 women (42%). Seventy-five adverse events (20%) were classified as serious (serious adverse events); occurring in 70 women. Intraoperative bladder perforation (15 events) occurred exclusively in the retropubic group. Neurologic adverse events were more common in the transobturator group than in retropubic (32 events vs 20 events, respectively). Twenty-three (4%) women experienced mesh complications, including delayed presentations, in both groups. CONCLUSION: Adverse events vary by procedure, but are common after midurethral sling. Most events resolve without significant sequelae.

Mechanisms of continence and surgical cure in female and male SUI: surgical research initiatives.

AIMS: To report the conclusions of the Think Tank on mechanisms of incontinence and surgical cure in female and male SUI: surgical research initiatives during the ICI-RS meeting in 2010. METHODS: The sub-group considered five areas for future research in stress urinary incontinence (SUI); (i) epidemiology and public health efforts in SUI, (ii) the basic sciences examining the physiology and pathophysiology of the continence mechanism, (iii) diagnostic techniques and clinical assessment of SUI, (iv) the future of treatment and surgical cure, and (v) the separate issue of male SUI. RESULTS: Roadblocks to progress were identified for each of the five directions. CONCLUSIONS: Future research directions are suggested for each of these areas.

Retropubic versus transobturator midurethral slings for stress incontinence.

BACKGROUND: Midurethral slings are increasingly used for the treatment of stress incontinence, but there are limited data comparing types of slings and associated complications. METHODS: We performed a multicenter, randomized equivalence trial comparing outcomes with retropubic and transobturator midurethral slings in women with stress incontinence. The primary outcome was treatment success at 12 months according to both objective criteria (a negative stress test, a negative pad test, and no retreatment) and subjective criteria (self-reported absence of symptoms, no leakage episodes recorded, and no retreatment). The predetermined equivalence margin was +/-12 percentage points. RESULTS: A total of 597 women were randomly assigned to a study group; 565 (94.6%) completed the 12-month assessment. The rates of objectively assessed treatment success were 80.8% in the retropubic-sling group and 77.7% in the transobturator-sling group (3.0 percentage-point difference; 95% confidence interval [CI], -3.6 to 9.6). The rates of subjectively assessed success were 62.2% and 55.8%, respectively (6.4 percentage-point difference; 95% CI, -1.6 to 14.3). The rates of voiding dysfunction requiring surgery were 2.7% in those who received retropubic slings and 0% in those who received transobturator slings (P=0.004), and the respective rates of neurologic symptoms were 4.0% and 9.4% (P=0.01). There were no significant differences between groups in postoperative urge incontinence, satisfaction with the results of the procedure, or quality of life. CONCLUSIONS: The 12-month rates of objectively assessed success of treatment for stress incontinence with the retropubic and transobturator approaches met the prespecified criteria for equivalence; the rates of subjectively assessed success were similar between groups but did not meet the criteria for equivalence. Differences in the complications associated with the two procedures should be discussed with patients who are considering surgical treatment for incontinence. (ClinicalTrials.gov number, NCT00325039.)

Significant linkage evidence for a predisposition gene for pelvic floor disorders on chromosome 9q21.

Predisposition factors for pelvic floor disorders (PFDs), including pelvic organ prolapse (POP), stress urinary incontinence (SUI), urge urinary incontinence (UUI), and hernias, are not well understood. We assessed linkage evidence for PFDs in mostly sister pairs who received treatment for moderate-to-severe POP. We genotyped 70 affected women of European descent from 32 eligible families with at least two affected cases by using the Illumina 1 million single-nucleotide polymorphism (SNP) marker set. Parametric linkage analysis with general dominant and recessive models was performed by the Markov chain Monte Carlo linkage analysis method, MCLINK, and a set of SNPs was formed, from which those in high linkage disequilibrium were eliminated. Significant genome-wide evidence for linkage was identified on chromosome 9q21 with a HLOD score of 3.41 under a recessive model. Seventeen pedigrees (53%) had at least nominal evidence for linkage on a by-pedigree basis at this region. These results provide evidence for a predisposition gene for PFDs on chromosome 9q.

Complications in women undergoing Burch colposuspension versus autologous rectus fascial sling for stress urinary incontinence.

PURPOSE: We determined the clinicodemographic factors associated with complications of continence procedures, the impact of concomitant surgery on the complication rate and the relationship between the incidence of cystitis and the method of postoperative bladder drainage. MATERIALS AND METHODS: We reviewed serious adverse events and adverse events in the Stress Incontinence Surgical Efficacy Trial, a randomized trial comparing Burch colposuspension to the autologous rectus fascial sling. Clinicodemographic variables were analyzed to determine those associated with adverse events using logistic regression analysis. Complications were stratified based on the presence or absence of concomitant surgery. Differences in complication rates (controlling for concomitant surgery) and cystitis rates (controlling for the bladder emptying method) were compared using Fisher's exact test. RESULTS: Blood loss (p = 0.0002) and operative time (p <0.0001) were significantly associated with an adverse event. Patients who underwent concomitant surgery had a significantly higher serious adverse event rate (14.2% vs 7.3%, p = 0.01) and adverse event rate (60.5% vs 48%, p <0.01) than patients who underwent continence surgery alone. Cystitis rates were higher in the sling vs the Burch group up to 6 weeks postoperatively regardless of concomitant surgery status (p <0.01). Intermittent self-catheterization increased the cystitis rate by 17% and 23% in the Burch and sling groups, respectively. CONCLUSIONS: Concomitant surgery at continence surgery increased the risk of complications. Sling surgery was associated with a higher risk of cystitis within the first 6 weeks postoperatively. Intermittent self-catheterization increased the risk of cystitis in each group. Complications were associated with surgical factors and not with patient related factors.

Risk factors for mesh/suture erosion following sacral colpopexy.

OBJECTIVE: The purpose of this study was to identify risks for mesh/suture erosions following abdominal sacral colpopexy (ASC). STUDY DESIGN: We analyzed demographic, perioperative variables, and erosion status in 322 participants in the Colpopexy and Urinary Reduction Efforts study 2 years after sacral colpopexy. RESULTS: The predominant graft used was synthetic mesh: woven polyester (Mersilene; Ethicon, Inc, Somerville, NJ) (42%) or polypropylene (48%). Twenty subjects (6%) experienced mesh/suture erosion. Unadjusted risk factors for mesh/suture erosion were expanded polytrafluroethylene (ePTFE) mesh (ePTFE 4/21 [19%] vs non-ePTFE 16/301 [5%]; odds ratio [OR], 4.2), concurrent hysterectomy (OR, 4.9), and current smoking (OR, 5.2). Of those with mesh erosion, most affected women (13/17) underwent at least 1 surgery for partial or total mesh removal. Two were completely resolved, 6 had persistent problems, and 5 were lost to follow-up. No resolution was documented in the 4 women who elected observation. CONCLUSION: Expanded PTFE mesh should not be used for sacral colpopexy. Concurrent hysterectomy and smoking are modifiable risks for mesh/suture erosion.

Two-year outcomes after surgery for stress urinary incontinence in older compared with younger women.

OBJECTIVE: To estimate whether perioperative and postoperative outcomes after Burch colposuspension or pubovaginal sling for stress urinary incontinence (SUI) differed with age. METHODS: This study was a prospective secondary analysis of the Stress Incontinence Surgical Treatment Efficacy Trial. Baseline characteristics, adverse events, and 2-year outcomes of women at least 65 years old were compared with those younger than 65 years using chi(2) and t tests. Multivariable analyses were performed, including age and outcomes that differed between age groups on univariable analysis, adjusting for variables that differed by age group at baseline and by surgical treatment group. RESULTS: Six-hundred fifty-five women were included in analyses of perioperative events and 520 for 2-year outcomes. Mean age (+/-standard deviation) was 69.7 (+/-3.7) years in the older group and 49.4 (+/-8.2) in the younger group. Older women had slightly longer time to normal activities (50 days compared with 42 days, P=.05), but there was no difference in time to normal voiding (14 days compared with 11 days, P=.42). Older women were more likely to have a positive stress test at follow-up (odds ratio [OR] 3.7, 95% confidence interval [CI] 1.70-7.97, P=.001), less subjective improvement in stress (8 point lesser decrease, 95% CI 1.5-14.1, P=.02), and urge incontinence (7 point lesser decrease, 95% CI 1.5-12.2, P=.01) by the Medical and Epidemiologic Social Aspects of Aging questionnaire, and were more likely to undergo surgical retreatment for SUI (OR 3.9, 95% CI 1.30-11.48). Perioperative adverse events and length of stay did not differ between groups. CONCLUSION: Older women undergoing surgery for stress incontinence can expect to do as well as younger women with respect to perioperative outcomes, but experience 2-year outcomes that are worse.

Duloxetine versus placebo for the treatment of North American women with stress urinary incontinence.

PURPOSE: Duloxetine, a selective serotonin and norepinephrine reuptake inhibitor, increases rhabdosphincter contractility via the stimulation of pudendal motor neuron alpha-1 adrenergic and 5-hydroxytryptamine-2 receptors. In this first phase 3 study we assessed the efficacy and safety of duloxetine in women with stress urinary incontinence (SUI). MATERIALS AND METHODS: A total of 683 North American women 22 to 84 years old were enrolled in this double-blind, placebo controlled study. The case definition included a predominant symptom of SUI with a weekly incontinence episode frequency (IEF) of 7 or greater, the absence of predominant symptoms of urge incontinence, normal diurnal and nocturnal frequency, a bladder capacity of 400 ml or greater, and a positive cough stress test and stress pad test. After a 2-week placebo lead-in period subjects were randomly assigned to receive placebo (339) or 80 mg duloxetine daily (344) as 40 mg twice daily for 12 weeks. Primary outcome variables included IEF and an incontinence quality of life questionnaire. Van Elteren's test was used to analyze percent changes in IEF with a stratification variable of weekly baseline IEF (less than 14 and 14 or greater). ANCOVA was used to analyze incontinence quality of life scores. RESULTS: Mean baseline IEF was 18 weekly and 436 subjects (64%) had a baseline IEF of 14 or greater. There was a significant decrease in IEF with duloxetine compared with placebo (50% vs 27%, p <0.001) with comparably significant improvements in quality of life (11.0 vs 6.8, p <0.001). Of subjects on duloxetine 51% had a 50% to 100% decrease in IEF compared with 34% of those on placebo (p <0.001). These improvements with duloxetine were associated with a significant increases in the voiding interval compared with placebo (20 vs 2 minutes, p <0.001) and they were observed across the spectrum of incontinence severity. The discontinuation rate for adverse events was 4% for placebo and 24% for duloxetine (p <0.001) with nausea the most common reason for discontinuation (6.4%). Nausea, which was also the most common side effect, tended to be mild to moderate and transient, usually resolving after 1 week to 1 month. Of the 78 women who experienced treatment emergent nausea while taking duloxetine 58 (74%) completed the trial. CONCLUSIONS: These phase 3 data are consistent with phase 2 data and they provide further evidence for the safety and efficacy of duloxetine as a pharmacological agent for the treatment of women with SUI.