Characteristics Associated With Clinically Important Treatment Responses in Women Undergoing Nonsurgical Therapy for Fecal Incontinence.

OBJECTIVE: To identify baseline clinical and demographic characteristics associated with clinically important treatment responses in a randomized trial of nonsurgical therapies for fecal incontinence (FI). METHODS: Women (N = 296) with FI were randomized to loperamide or placebo- and manometry-assisted biofeedback exercises or educational pamphlet in a 2 × 2 factorial design. Treatment response was defined in 3 ways from baseline to 24 weeks: minimal clinically important difference (MID) of -5 points in St. Mark's score, ≥50% reduction in FI episodes, and combined St. Mark's MID and ≥50% reduction FI episodes. Multivariable logistic regression models included baseline characteristics and treatment groups with and without controlling for drug and exercise adherence. RESULTS: Treatment response defined by St. Mark's MID was associated with higher symptom severity (adjusted odds ratio [aOR] 1.20, 95% confidence interval [CI] 1.11-1.28) and being overweight vs normal/underweight (aOR 2.15, 95% CI 1.07-4.34); these predictors remained controlling for adherence. Fifty percent reduction in FI episodes was associated with the combined loperamide/biofeedback group compared with placebo/pamphlet (aOR 4.04, 95% CI 1.36-11.98), St. Mark's score in the placebo/pamphlet group (aOR 1.29, 95% CI 1.01-1.65), FI subtype of urge vs urge plus passive FI (aOR 2.39, 95% CI 1.09-5.25), and passive vs urge plus passive FI (aOR 3.26, 95% CI 1.48-7.17). Controlling for adherence, associations remained, except St. Mark's score. DISCUSSION: Higher severity of FI symptoms, being overweight, drug adherence, FI subtype, and combined biofeedback and medication treatment were associated with clinically important treatment responses. This information may assist in counseling patients, regarding efficacy and expectations of nonsurgical treatments of FI.

Contribution of the second stage of labour to pelvic floor dysfunction: a prospective cohort comparison of nulliparous women.

OBJECTIVE: Maternal expulsive efforts are thought to damage the pelvic floor. We aimed to compare pelvic floor function and anatomy between women who delivered vaginally (VB) versus those with caesarean delivery (CD) prior to the second stage of labour. DESIGN: Prospective cohort. SETTING: University Hospital Midwifery practice. POPULATION: Nulliparas. METHODS: Pregnant nulliparas were recruited during pregnancy and women who underwent CD prior to the 2nd stage of labour at birth were recruited immediately postpartum. Both groups were followed prospectively to 6 months postpartum. MAIN OUTCOME MEASURES: POPQ, perineal ultrasound (U/S) and Paper Towel Test (PTT), an objective measure of stress incontinence; Incontinence Severity Index (ISI), Pelvic Floor Impact Questionnaire (PFIQ-7), Wexner Fecal Incontinence Scale (W) and Female Sexual Function Index (FSFI). RESULTS: 336/448 (75%) VB and 138/224 (62%) CD followed up. The VB group was younger (23.9 ± 4.9 versus 26.6 ± 6.1 years, P < 0.001) and less overweight/obese (38 versus 56%, P < 0.001); baseline functional measures were similar (all P > 0.05). At follow-up, urinary incontinence (UI) (55 versus 46% ISI > 0, P = 0.10), fecal incontinence (FI) (8 versus 13% FI on W, P = 0.12), sexual activity rates (88 versus 92%, P = 0.18) and PFIQ-seven scores were similar. Positive PTT tests (17 versus 6%, P = 0.002) and ≥ Stage 2 prolapse (22 versus 15%, P = 0.03) were higher with VB; differences were limited to points Aa and Ba. U/S findings were not different between groups. Stepwise multivariate analyses controlling for age, body mass index, and non-Hispanic White race for prolapse of points Aa and Ba did not alter conclusions (all P < 0.004). CONCLUSIONS: VB resulted in prolapse changes and objective UI but not in increased self-report pelvic floor dysfunction at 6 months postpartum compared with women who delivered by CD prior to the second stage of labour. The second stage of labour had a modest effect on postpartum pelvic floor function.

The minimum important difference for the Pelvic Organ Prolapse-Urinary Incontinence Sexual Function Questionnaire.

INTRODUCTION AND HYPOTHESIS: Although the Pelvic Organ Prolapse-Urinary Incontinence Sexual Function Questionnaire (PISQ) is widely used to assess sexual function in women, the minimum important difference (MID) (defined as the smallest difference in scores of a patient-reported outcome measure that is perceived by patients as beneficial or harmful and which would lead the clinician to consider a change in treatment) is not known. The objective was to estimate the MID for the PISQ. METHODS: Two study populations, one of women with overactive bladder (OAB) and urgency UI (UUI) treated with tolterodine in a placebo-controlled trial (cohort I), and one of women treated surgically for prolapse and/or UI (cohort II) were used. Cohort I anchors were the Overactive Bladder Questionnaire (OAB-q), the Patient Perception of Bladder Condition (PPBC), the Patient Perception of Treatment Benefit Questionnaire (PPTBQ), and the change in number of UUI episodes in bladder diaries. Distribution MIDs were also calculated. RESULTS: In the anchor-based analysis, the MID values for changes in PISQ total scores at 3 months in cohort I were 5 points using the UUI anchor (diary-dry women), 5 points using the PPBC anchor, 5 points with the PPTBQ, and 9 points with the OAB-q. In cohort II, the MID at week 12 in PISQ total scores was 7 points in women with improved IIQ-7 scores. The distribution-based MID in PISQ total scores was 5.3 points in cohort I and 5.8 points in cohort II. CONCLUSION: A reasonable estimate of MID for the PISQ total score is 6 points. Improvements that meet these thresholds may be considered clinically important.

A new measure of sexual function in women with pelvic floor disorders (PFD): the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR).

INTRODUCTION AND HYPOTHESIS: The objective of this study was to create a valid, reliable, and responsive sexual function measure in women with pelvic floor disorders (PFDs) for both sexually active (SA) and inactive (NSA) women. METHODS: Expert review identified concept gaps and generated items evaluated with cognitive interviews. Women underwent Pelvic Organ Prolapse Quantification (POPQ) exams and completed the Incontinence Severity Index (ISI), a prolapse question from the Epidemiology of Prolapse and Incontinence Questionnaire (ISI scores), the Pelvic Floor Distress Inventory-20 (PFDI-20), and the Female Sexual Function Index (FSFI). Principle components and orthogonal varimax rotation and principle factor analysis with oblique rotation identified item grouping. Cronbach's alpha measured internal consistency. Factor correlations evaluated criterion validation. Change scores compared to change scores in other measures evaluated responsiveness among women who underwent surgery. RESULTS: A total of 589 women gave baseline data, 200 returned surveys after treatment, and 147 provided test-retest data. For SA women, 3 subscales each in 2 domains (21 items) and for NSA women 2 subscales in each of 2 domains (12 items) emerged with robust psychometric properties. Cronbach's alpha ranged from .63 to .91. For SA women, correlations were in the anticipated direction with PFDI-20, ISI, and FSFI scores, POPQ, and EPIQ question #35 (all p < .05). PFDI-20, ISI, and FSFI subscale change scores correlated with Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire International Urogynecological Association-revised (PISQ-IR) factor change scores and with mean change scores in women who underwent surgery (all p < .05). For NSA women, PISQ-IR scores correlated with PFDI-20, ISI scores, and with EPIQ question #35 (all p < .05). No items demonstrated differences between test and retest (all p ≥ .05), indicating stability over time. CONCLUSIONS: The PISQ-IR is a valid, reliable, and responsive measure of sexual function.

Obesity and retropubic surgery for stress incontinence: is there really an increased risk of intraoperative complications?

OBJECTIVE: The objective of the study was to evaluate the impact of obesity on length of surgery, blood loss, and intra- and postoperative complications in women who underwent retropubic surgery for stress urinary incontinence. STUDY DESIGN: Of 449 women participating in a multicenter, randomized trial evaluating antibiotic prophylaxis in women with suprapubic catheters, 250 women underwent retropubic anti-incontinence procedures. This is a prospective nested cohort study of these women, 79 (32%) of whom were obese (body mass index 30 or greater) and 171 (68%) overweight or normal weight (body mass index less than 30). Data collected included demographic variables, past medical history, physical examination, and intraoperative and postoperative complications. Data were analyzed with Fisher's exact for dichotomous variables, Student t tests for continuous variables, and analysis of variance for multivariate analysis. Significance was set at P < .05. RESULTS: Obese women undergoing stress urinary incontinence surgery were younger than nonobese women (48.7 versus 51.9 years, respectively, P < .019). The number and type of additional surgeries performed were similar between groups with the exception that obese women were less likely to undergo abdominal apical suspensions (P = .006) or abdominal paravaginal repairs (P = .001); therefore, estimated blood loss, change in hematocrit, length of stay, surgery, and suprapubic catheterization comparisons are adjusted for the performance of these procedures. Estimated surgical blood loss was greater for obese women (344 versus 284 P = .03); however, change in hematocrit was lower for obese than nonobese women (6.6 versus 7.3, P = .048). Mean length of surgery was 15 minutes longer in obese women (P = .02). Length of hospital stay did not vary between groups (P = NS). Major intraoperative complications were uncommon (14 [5.6%]), with no difference between weight groups. Incidence of postoperative urinary tract infection, wound infections, or postoperative major complications were likewise similar between groups (all P > .05). CONCLUSION: Surgery takes longer for obese patients, but blood loss as recorded by change in hematocrit is lower. Major complications were rare and similar between weight groups, as were infectious complications.

Neighbourhoods and homicide mortality: an analysis of race/ethnic differences.

OBJECTIVE: To examine whether measures of neighbourhood economic deprivation, social disorganisation, and acculturation explain homicide mortality differentials between Mexican Americans, non-Hispanic black Americans, and non-Hispanic white Americans, net of individual factors. DESIGN: Prospective study, National Health Interview Survey (1986-1994) linked to subsequent mortality in the National Death Index (1986-1997). SETTING: United States of America. PARTICIPANTS: A nationally representative sample of non-institutionalised Mexican Americans, non-Hispanic black Americans, and non-Hispanic white Americans, aged 18-50 at the point of interview. ANALYSIS: Cox proportional hazard models estimate the risk of death associated with various neighbourhood and individual factors. MAIN RESULTS: Both individual and neighbourhood risk factors partially account for race/ethnic disparities in homicide. Homicide mortality risks are between 20% and 50% higher for residents of areas that have economic inequality of 0.50 or greater based on the coefficient of variation, or where 4% or more of the residents are Mexican American, 10% or more of the residents are non-Hispanic black, or 20% or more of the households are headed by single parents (p< or = 0.05). But residents of areas where 10% or more of their neighbours are foreign born have 35% lower mortality risks than people living in areas with fewer foreign born people (p< or =0.05). These differences persist even after controlling for individual level risk factors. CONCLUSIONS: The findings support economic deprivation, social disorganisation, and acculturation theories, and suggest that both neighbourhood and individual risk factors affect race/ethnic differences in homicide mortality. Public health policies must focus on both individual and neighbourhood factors to reduce homicide risks in vulnerable populations.

Vaginal erosion of cadaveric fascia lata following abdominal sacrocolpopexy and suburethral sling urethropexy.

The aim of this paper is to report vaginal erosion of cadaveric fascia lata used for abdominal sacrocolpopexy and suburethral sling urethropexy. The charts of patients who underwent abdominal sacrocolpopexy or suburethral sling urethropexy between March 1994 and February 1999 were reviewed for perioperative data. In 47 cases of abdominal sacrocolpopexy or suburethral sling, 32 utilized cadaveric fascia lata, with 11 for sacrocolpopexy and 22 for suburethral sling. Vaginal erosion of cadaveric fascia lata graft was noted in 5 (23%) following sling procedure and 3 (27%) following sacrocolpopexy, diagnosed a mean of 36.8 days (+/- 7.1, range 27-45) following surgery. These women were treated conservatively with estrogen vaginal cream, and both vaginal and oral antibiotics. Four of the 8 (50%) underwent excision of the exposed graft and reapproximation of the vaginal edges under local anesthesia, whereas the remainder responded to medical therapy alone. None of the patients experienced recurrence of vaginal vault prolapse or urinary incontinence following graft erosion. Comparison of women with vaginal erosion of cadaveric fascia lata to those without revealed an association with perioperative febrile morbidity (P=0.04), but not with age, hormonal or insurance status, body mass index, history of diabetes mellitus or smoking, length of surgery, estimated blood loss, change in hematocrit, or other perioperative complications. Vaginal erosion of cadaveric fascia lata utilized for abdominal sacrocolpopexy and suburethral sling was noted in 25% of our patients and may have an infectious etiology. Conservative treatment with antibiotics and estrogen is effective, but removal of exposed graft with vaginal closure may be necessary.

Vasopressin as an etiologic factor for infection in gynecologic surgery: a randomized double-blind placebo-controlled trial.

OBJECTIVE: The purpose of this study was to evaluate the risk of pelvic infection with the use of vasopressin at time of vaginal hysterectomy with a randomized controlled trial. STUDY DESIGN: Women who underwent vaginal hysterectomy and agreed to participate were randomly assigned to pericervical injections of vasopressin or normal saline solution. Surgeons and patients were blinded to the injected substance. Power analysis revealed that a sample size of 116 patients would be sufficient to detect a 4-fold difference in pelvic infection rates between the 2 groups, with 90% power and a probability value of.05. RESULTS: Analysis with 117 patients found no difference in infection rate between the normal saline solution group and the vasopressin groups (7.3% vs 1.6%; P =.19). Estimated blood loss (312 +/- 222 mL vs 446 +/- 296 mL; P =.006) and change in hemoglobin and hematocrit levels (2.1 +/- 1.4 gm vs 2.9 +/- 1.4 gm; P: =.02; and 6.7% +/- 3.4% vs 8.5% +/- 3.8%; P =.01; vasopressin versus normal saline solution, respectively) were significantly less in the vasopressin group. There were no significant differences in interval blood pressure measurements after vasopressin administration between the 2 groups. CONCLUSION: The use of vasopressin during vaginal hysterectomy does not increase the risk of pelvic infection, does decrease operative blood loss, and does not significantly affect blood pressure.

A new instrument to measure sexual function in women with urinary incontinence or pelvic organ prolapse.

OBJECTIVE: Our aim was to develop a condition-specific, reliable, validated, and self-administered instrument to evaluate sexual function in women with pelvic organ prolapse or urinary incontinence. STUDY DESIGN: The questionnaire was designed after review of the literature and of nonspecific validated instruments. The study was completed in 2 phases. In phase 1 a total of 83 women completed both our questionnaire and the Incontinence Impact Questionnaire-7, with 20 women undergoing test-retest reliability analyses. Item analysis was based on the internal consistency, the correlations with the Incontinence Impact Questionnaire-7, the patient's age and self-rating of satisfaction, and the results of reliability testing. For final validation the questionnaire was administered in phase 2 to 99 women. Factor and item analyses were repeated, results were correlated with the Sexual History Form-12, and comparison was made between patients with high depression scores and those with low depression scores on the Symptom Questionnaire. RESULTS: Factor analysis identified 3 domains, labeled Behavioral/Emotive, Physical, and Partner-Related. Sexual function scores were highly correlated with scores on the Sexual History Form-12 for the questionnaire (r = -0.74; P <.001) and for both the Behavioral/Emotive and the Partner-Related domains (r = -0.79 and -0.5, respectively; P <.001). The Physical domain was correlated with scores on the Incontinence Impact Questionnaire-7 (r = -0.63; P <.001). Women with high depression scores on the Symptom Questionnaire had significantly lower scores on the final questionnaire, in comparison with women without depression (P <.001). CONCLUSION: We developed a condition-specific, validated, and reliable instrument, containing 31 items divided into 3 domains, to evaluate sexual functioning in women with urinary incontinence or pelvic organ prolapse.

Medical vs. Surgical treatment of ectopic pregnancy. The University of New Mexico's six-year experience.

OBJECTIVE: To review and compare the treatments for ectopic pregnancy in a university setting serving an indigent population. STUDY DESIGN: Charts assigned an ICD-9 code for ectopic pregnancy from January 1, 1993, through December 31, 1998, were reviewed for presenting symptoms, hCG levels, ultrasound findings, treatment modality and need for subsequent treatment. RESULTS: Of 401 patients treated for ectopic pregnancy, 7 were managed expectantly. One hundred nineteen (30%) patients received methotrexate. Seventy percent (83/119) of these ectopic pregnancies resolved with a single dose and an additional 11 after a second dose, for a 79% overall success rate. Twenty-five patients (21%) failed methotrexate therapy and required surgical treatment, and 11 (9%) pregnancies were ruptured. Primary treatment was surgical in 275 (69%) patients: 172 (63%) underwent laparoscopy and 103 (37%) laparotomy. Primary laparoscopic treatment was successful in 90%. Success rates were significantly lower for medical therapy as compared to laparoscopic treatment (79% vs. 90%, odds ratio 2.2, 95% confidence interval 1.1, 4.3; P = .02). No discriminating predictors of successful treatment with methotrexate were identified. CONCLUSION: The success rate of methotrexate therapy for ectopic pregnancy was lower than that of surgical management in a university setting serving an indigent population.

Early feeding and the incidence of gastrointestinal symptoms after major gynecologic surgery.

OBJECTIVE: To compare early feeding with traditional postoperative dietary management for development of postoperative gastrointestinal symptoms, including ileus after major gynecologic surgery for benign conditions. METHODS: Women who had major gynecologic surgery for benign conditions were randomly allocated to early feeding of low residue diets 6 hours postoperatively or traditional dietary management of clear liquids with normal bowel sounds, and regular diet with passage of flatus. Demographic and perioperative data were collected, and patients answered questionnaires on their perception of bowel function and pain using the McGill Pain Scale. Power analysis found that 130 women were needed to find a twofold greater incidence of ileus in the early feeding group with 80% power and alpha =.05. RESULTS: Complete data were available for 139 women, 67 allocated to the early feeding group and 72 to the late feeding group. The incidence of postoperative ileus for the study population was 4.4% and did not differ between groups (early 3% versus late 5. 8%, P =.68). There were no differences in patient demographics, surgical procedures, anesthesia used, and intraoperative complications between groups. With the exception of more complaints of nausea in the late feeding group (23% versus 13%, P =.04), there were no differences in other postoperative variables, including other perioperative complications, pain medicine requirements, fluid and caloric intake, median pain scores, and gastrointestinal function. The low incidence of perioperative complications made the power to detect differences between groups low. CONCLUSION: Low residue diet 6 hours after major gynecologic surgery for benign indications was not associated with increased postoperative gastrointestinal complaints, including ileus.

Eliminating superfluous neighbor pairs while threading fold models.

In this paper we address the problem of identifying which of various possible spatial residue-residue neighbor pairs are plausible physical contacts without reference to the native structure side chain geometry. We propose an algorithm that eliminates most of the implausible physical contacts from the fold models. This algorithm exploits the correlations between the amino acid side chain rotamers and the direction of the physical contacts between the amino acid side chains. We use this algorithm to "filter" the score of the sequence-to-structure alignment. Filtering is dynamic, in the sense that the set of neighbor pairs contributing to the alignment score varies during threading. Whether or not a neighbor pair contributes to the score depends on the threaded amino acids. This score filtering improves the accuracy of the predicted sequence-to-structure alignment.

Protein fold recognition by total alignment probability.

We present a protein fold-recognition method that uses a comprehensive statistical interpretation of structural Hidden Markov Models (HMMs). The structure/fold recognition is done by summing the probabilities of all sequence-to-structure alignments. The optimal alignment can be defined as the most probable, but suboptimal alignments may have comparable probabilities. These suboptimal alignments can be interpreted as optimal alignments to the "other" structures from the ensemble or optimal alignments under minor fluctuations in the scoring function. Summing probabilities for all alignments gives a complete estimate of sequence-model compatibility. In the case of HMMs that produce a sequence, this reflects the fact that due to our indifference to exactly how the HMM produced the sequence, we should sum over all possibilities. We have built a set of structural HMMs for 188 protein structures and have compared two methods for identifying the structure compatible with a sequence: by the optimal alignment probability and by the total probability. Fold recognition by total probability was 40% more accurate than fold recognition by the optimal alignment probability. Proteins 2000;40:451-462.

Active management of labor: a cost analysis of a randomized controlled trial.

OBJECTIVE: To compare the costs of a protocol of active management of labor with those of traditional labor management. DESIGN: Cost analysis of a randomized controlled trial. METHODS: From August 1992 to April 1996, we randomly allocated 405 women whose infants were delivered at the University of New Mexico Health Sciences Center, Albuquerque, to an active management of labor protocol that had substantially reduced the duration of labor or a control protocol. We calculated the average cost for each delivery, using both actual costs and charges. RESULTS: The average cost for women assigned to the active management protocol was $2,480.79 compared with an average cost of $2,528.61 for women in the control group (P = 0.55). For women whose infant was delivered by cesarean section, the average cost was $4,771.54 for active management of labor and $4,468.89 for the control protocol (P = 0.16). Spontaneous vaginal deliveries cost an average of $27.00 more for actively managed patients compared with the cost for the control protocol. CONCLUSIONS: The reduced duration of labor by active management did not translate into significant cost savings. Overall, an average cost saving of only $47.91, or 2%, was achieved for labors that were actively managed. This reduction in cost was due to a decrease in the rate of cesarean sections in women whose labor was actively managed and not to a decreased duration of labor.

Overactive bladder significantly affects quality of life.

Overactive bladder (OAB), with symptoms of frequency, urgency, and urge incontinence, substantially affects the lives of millions of people. The symptoms associated with OAB can significantly affect the social, psychological, occupational, domestic, physical, and sexual aspects of those who suffer from it. Unfortunately, many sufferers are reluctant to discuss their condition with their healthcare provider or family members. As a result, OAB remains underreported, despite increased awareness and improved diagnosis and treatment. Health-related quality of life can be measured objectively, and several instruments have been developed, validated, and used in research. Currently, there are 2 major types of quality-of-life questionnaires: generic and disease specific. Although these questionnaires have been helpful and are widely used, the goal is to establish a single questionnaire that is acceptable throughout the world for use by urologists, gynecologists, urogynecologists, geriatricians, and epidemiologists.

Filtered neighbors threading.

We present a knowledge-based threading scoring function that exploits the information about protein structure contained in residue packing/neighbor preferences. The proposed algorithm eliminates the stereochemically improbable physical contacts for each possible sequence-to-structure alignment. We use this algorithm to "filter" the score of the sequence-to-structure alignment. Filtering is dynamic, in the sense that the set of neighbor pairs contributing to the alignment score varies during threading. Whether or not a neighbor pair contributes to the score depends on the threaded amino acids. We use a detailed structure description that encodes amino acid side-chain rotamer and physical contact preferences but does not imprint the fold model with the native sequence or native physical contacts. We discretize this description to collect accurate statistics for the scoring function generation. We use the original detailed description for the neighbor filtering. On average, the filtered neighbors threading (FNT) method predicts the sequence-to-structure alignment twice as accurately as does the "standard" unfiltered neighbors threading. For the set of threadings tested by the PHDthreader method, the FNT gives predictions with a sequence-to-structure alignment accuracy of 46.9%, which amounts to a 74% improvement in alignment sensitivity compared with PHDthreader predictions. These results show that reduction of noise from the observed neighbor pair preferences by filtering leads to noticeable improvements in the predicted sequence-to-structure alignments.