Added Value of Next Generation over Sanger Sequencing in Kenyan Youth with Extensive HIV-1 Drug Resistance.

HIV-1 drug resistance testing in children and adolescents in low-resource settings is both important and challenging. New (more sensitive) drug resistance testing technologies may improve clinical care, but evaluation of their added value is limited. We assessed the potential added value of using next-generation sequencing (NGS) over Sanger sequencing for detecting nucleoside reverse transcriptase inhibitor (NRTI) and nonnucleoside reverse transcriptase inhibitor (NNRTI) drug resistance mutations (DRMs). Participants included 132 treatment-experienced Kenyan children and adolescents with diverse HIV-1 subtypes and with already high levels of drug resistance detected by Sanger sequencing. We examined overall and DRM-specific resistance and its predicted impact on antiretroviral therapy and evaluated the discrepancy between Sanger sequencing and six NGS thresholds (1%, 2%, 5%, 10%, 15%, and 20%). Depending on the NGS threshold, agreement between the two technologies was 62% to 88% for any DRM, 83% to 92% for NRTI DRMs, and 73% to 94% for NNRTI DRMs, with more DRMs detected at low NGS thresholds. NGS identified 96% to 100% of DRMs detected by Sanger sequencing, while Sanger identified 83% to 99% of DRMs detected by NGS. Higher discrepancy between technologies was associated with higher DRM prevalence. Even in this resistance-saturated cohort, 12% of participants had higher, potentially clinically relevant predicted resistance detected only by NGS. These findings, in a young, vulnerable Kenyan population with diverse HIV-1 subtypes and already high resistance levels, suggest potential benefits of more sensitive NGS over existing technology. Good agreement between technologies at high NGS thresholds supports their interchangeable use; however, the significance of DRMs identified at lower thresholds to patient care should be explored further. IMPORTANCE HIV-1 drug resistance in children and adolescents remains a significant problem in countries facing the highest burden of the HIV epidemic. Surveillance of HIV-1 drug resistance in children and adolescents is an important public health strategy, particularly in resource-limited settings, and yet, it is limited due mostly to cost and infrastructure constraints. Whether newer and more sensitive next-generation sequencing (NGS) adds substantial value beyond traditional Sanger sequencing in detecting HIV-1 drug resistance in real life settings remains an open and debatable question. In this paper, we attempt to address this issue by performing a comprehensive comparison of drug resistance identified by Sanger sequencing and six NGS thresholds. We conducted this study in a well-characterized, vulnerable cohort of children and adolescents living with diverse HIV-1 subtypes in Kenya and, importantly, failing antiretroviral therapy (ART) with already extensive drug resistance. Our findings suggest a potential added value of NGS over Sanger even in this unique cohort.

A longitudinal analysis of hospitalization and emergency department use among human immunodeficiency virus-infected women reporting protease inhibitor use.

The impact of protease inhibitors (PIs) on emergency department (i.e., emergency room [ER]) visits and hospitalizations was examined among a cohort of human immunodeficiency virus (HIV)-infected and high-risk women followed-up in the HIV Epidemiology Research Study (HERS) from 1993 through 1999. The rates of hospitalization and ER visits were measured as a function of recent or current PI use, age, race, transmission risk category, HERS site, baseline CD4 cell count, and baseline virus load; the PI effect was estimated separately by baseline CD4 cell count. In the HERS, PI use was strongly associated with lower rates of ER visits and hospitalizations for patients with baseline CD4 cell counts of <200 cells/mL (for hospitalizations: rate ratio [RR], 0.54; 95% confidence interval [CI], 0.33-0.89; for ER visits: RR, 0.38; 95% CI, 0.24-0.61). Other factors associated with increased hospitalization and ER use included history of injection drug use, low CD4 cell counts, and high virus loads.

Antiretroviral regimen complexity, self-reported adherence, and HIV patients' understanding of their regimens: survey of women in the her study.

BACKGROUND: Research regarding treatment adherence in chronic diseases, such as hypertension, suggests that increasing complexity in the medication regimen is associated with decreasing patient adherence. However, less is known about the relationship between regimen complexity and adherence in the treatment of HIV/AIDS. OBJECTIVE: To examine the relationship between antiretroviral (ART) regimen complexity and patient understanding of correct regimen dosing to adherence (missing doses in the past 1 and 3 days). METHODS: Cross-sectional survey of a cohort of women living with HIV/AIDS and enrolled in the HER (HIV Epidemiologic Research) Study. RESULTS: Seventy-five percent of patients correctly understood the dosing frequency of their ART medications, 80% understood the food-dosing restrictions, whereas only 63% understood both. The percentage of patients with a correct understanding of dosing decreased with increasing regimen complexity (increased dosing frequency and food-dosing restrictions). Patients were more likely to have missed doses in the previous 3 days if they were taking ART medications three or more times per day or had to take one or more antiretrovirals on an empty stomach. A multivariate logistic regression model demonstrated that patients with less complex regimens (twice daily or less in frequency, no food-dosing restrictions) who correctly understood the dosing and food restrictions of their ART regimen were less likely to have skipped doses in the past three days (odds ratio [OR], 0.4; 95% confidence interval [CI], 0.2-0.7) than those with more complex regimens. Younger age and higher CD4 count were also associated with a reduced likelihood of skipping doses. No association was found between adherence and race/ethnicity, current or past injection drug use, or education. CONCLUSIONS: Self-reported adherence is better among patients with less complex ART regimens. This is in part because patients' understanding of regimen dosing decreases as regimen complexity increases. Therefore, simplifying antiretroviral regimens may have an important role in improving patients' adherence.

A statewide assessment of lead screening histories of preschool children enrolled in a Medicaid managed care program.

OBJECTIVES: Despite the prominence of lead poisoning as a public health problem, recent Government Accounting Office reports indicate that only one fifth of children who are covered by Medicaid have been screened for lead poisoning. The purpose of this study was to examine the lead screening histories of children who were enrolled in a statewide, Medicaid managed care plan to determine the relative impact of the type of primary care provider site and family sociodemographic characteristics on the likelihood of being screened. The study also examined the prevalence of and risk factors for lead poisoning of children who had been screened. METHODS: A random sample of 2000 preschool-age children was chosen from those who were enrolled continuously in the statewide, expanded, Medicaid managed care program for a 1-year period and between the ages of 19 and 35 months at the end of that year. Sociodemographic characteristics and lists of primary care providers were obtained from administrative data sets. Medical record audits at primary care provider sites were performed to obtain the lead screening histories of the children, including test dates and results. RESULTS: Data on 1988 children were used for study analyses, and 80% of these children had at least 1 documented blood lead level. Children whose primary care provider was an office-based physician were less likely to be screened as compared with patients of health centers, hospital-based clinics, and staff model health maintenance organizations (68%, 86%, 89%, and 91% respectively). Variation in screening rates persisted in a multivariate analysis controlling for family sociodemographic characteristics and practice level variation. Of the 1587 children who had a documented blood lead test, 467 children (29%) had a blood lead level of >/=10 mg/dL on at least 1 test. CONCLUSIONS: Blood lead screening rates in Rhode Island's Medicaid managed care program are dramatically higher than national estimates for children who are enrolled in Medicaid. Potential explanations for this finding are 1) a high sensitization to the problem of lead poisoning in Rhode Island, 2) the primary care focus of the Medicaid program in Rhode Island facilitates the delivery of preventive services, and 3) the medical record audit approach used in this study was more comprehensive in identifying blood lead screens than techniques used in national studies. The high prevalence of elevated blood lead levels found in this study emphasizes the importance of screening among children who are enrolled in Medicaid.

Association between bacterial vaginosis and expression of human immunodeficiency virus type 1 RNA in the female genital tract.

We assessed the effect of lower genital tract infections on human immunodeficiency virus type 1 (HIV-1) RNA shedding in the female genital tract. Bacterial vaginosis was significantly associated with HIV-1 RNA expression in the female genital tract of HIV-infected women.

On the wrong side of the tracts? Evaluating the accuracy of geocoding in public health research.

OBJECTIVES: This study sought to determine the accuracy of geocoding for public health databases. METHODS: A test file of 70 addresses, 50 of which involved errors, was generated, and the file was geocoded to the census tract and block group levels by 4 commercial geocoding firms. Also, the "real world" accuracy of the best-performing firm was evaluated. RESULTS: Accuracy rates in regard to geocoding of the test file ranged from 44% (95% confidence interval [CI] = 32%, 56%) to 84% (95% CI = 73%, 92%). The geocoding firm identified as having the best accuracy rate correctly geocoded 96% of the addresses obtained from the public health databases. CONCLUSIONS: Public health studies involving geocoded databases should evaluate and report on methods used to verify accuracy.

Amniotic fluid insulin at 14-20 weeks' gestation: association with later maternal glucose intolerance and birth macrosomia.

OBJECTIVE: To examine the hypothesis that early second trimester amniotic fluid (AF) insulin concentration is elevated and later fetal growth is augmented in gravidas demonstrating later oral glucose intolerance. RESEARCH DESIGN AND METHODS: In this prospective observational cohort study, AF was sampled at 14-20 weeks' gestation in 247 subjects, and 1-h 50-g oral glucose challenge tests (GCTs) were performed at > or = 24 weeks. AF insulin was assayed by an automated immuno-chemiluminometric assay (8). Macrosomia was defined as birth weight above the 90th centile. RESULTS: AF insulin concentration (range 1.4-44.5 pmol/l) correlated positively with gestational age and maternal weight. A logistic regression analysis, adjusted for maternal age and midpregnancy weight, showed increased AF insulin multiples of gestational age-specific medians to be associated with subsequently diagnosed gestational diabetes mellitus (GDM) (OR 1.9, CI 1.3-2.4, P = 0.029). Among 60 subjects with GCT values > 7.2 mmol/l, each unit increase in AF insulin multiple of median (MOM) was associated with a threefold increase in fetal macrosomia incidence (3.1, 1.3-4.9, P = 0.048). CONCLUSIONS: An elevated AF insulin concentration at 14-20 weeks' gestation is associated with subsequently documented maternal glucose intolerance. Among gravidas with GCT values > 7.2 mmol/l, elevated early AF insulin concentration is associated with fetal macrosomia. Maternal glucose intolerance may affect fetal insulin production before 20 weeks' gestation.

Midpregnancy serum C-peptide concentration and subsequent pregnancy-induced hypertension.

OBJECTIVE: To test the hypothesis that elevated midpregnancy serum insulin (IRI) and C-peptide (CP) concentrations are associated with later development of pregnancy-induced hypertension (PIH), independent of prepregnancy obesity and midpregnancy blood pressure. RESEARCH DESIGN AND METHODS: In this prospective study, a cohort of normotensive women, ages > or = years performed a 50-g glucose challenge test at 24-30 weeks' gestational age. Blood samples were collected after an overnight fast and 1 h after glucose ingestion. Serum IRI and CP concentrations were measured in each sample. Maternal height, blood pressure and proteinuria were measured at the time of glucose challenge testing and after 36 weeks' gestational age. RESULTS: Of 320 subjects enrolled 44 women (13.8%) had subsequent PIH. Crude odds ratios (ORs) for devevelopment of PIH associated with each 1 U rise in log fasting IRI, log lasting CP. and glucosed-induced increase in CP (expressed as log [postprandial CP/fasting CP]) were 2.0 (95% CI 1.3-3.3), 1.8 (CI 1.2-2.7), and 2.3 (CI 1.1-4.9) respectively. After controlling for prepregnancy BMI, gestational age, and midpregnancy mean arterial pressure, adjusted ORs corresponding to log fastig IRI and CP for the development of PIH were 1.3 (95% CI 0.7-2.3) and 1.7 (CI 1.1-2.7) respectively, and, afterq adjustment for fasting CP, the adjusted OR of the glucose-induced rise in log CP was 3.7 (CI 1.5-9.3). CONCLUSIONS: Mid-pregnancy tasting and postoral glucose CP levels are associated with subsequent development of PIH, independent of maternal obesity and midpregnancy baseline blood pressure. These findings many reflect an amplified beta3-cell response to glycemic stimulus, similar to that found in states of insulin resistance, that appears to be independently associated with PIH.

Reparameterizing the pattern mixture model for sensitivity analyses under informative dropout.

Pattern mixture models are frequently used to analyze longitudinal data where missingness is induced by dropout. For measured responses, it is typical to model the complete data as a mixture of multivariate normal distributions, where mixing is done over the dropout distribution. Fully parameterized pattern mixture models are not identified by incomplete data; Little (1993, Journal of the American Statistical Association 88, 125-134) has characterized several identifying restrictions that can be used for model fitting. We propose a reparameterization of the pattern mixture model that allows investigation of sensitivity to assumptions about nonidentified parameters in both the mean and variance, allows consideration of a wide range of nonignorable missing-data mechanisms, and has intuitive appeal for eliciting plausible missing-data mechanisms. The parameterization makes clear an advantage of pattern mixture models over parametric selection models, namely that the missing-data mechanism can be varied without affecting the marginal distribution of the observed data. To illustrate the utility of the new parameterization, we analyze data from a recent clinical trial of growth hormone for maintaining muscle strength in the elderly. Dropout occurs at a high rate and is potentially informative. We undertake a detailed sensitivity analysis to understand the impact of missing-data assumptions on the inference about the effects of growth hormone on muscle strength.

Progesterone, inhibin, and hCG multiple marker strategy to differentiate viable from nonviable pregnancies.

OBJECTIVE: To determine whether a combination of serum and urine biomarkers drawn from symptomatic pregnant women will help early differentiation of viable from nonviable pregnancies. METHODS: We conducted a prospective cohort study of 220 women who presented in the first trimester of pregnancy with complaints of pain, cramping, bleeding, or spotting. Serum samples for progesterone, inhibin A, and hCG, and urine beta-core hCG, were collected at presentation. To evaluate whether those biomarkers could predict viable and nonviable outcomes in pregnancy, we used likelihood ratios to compare operating characteristics of single and multiple biomarker strategies. RESULTS: Of 220 pregnancies studied, 98 were viable and 122 nonviable. Among single biomarkers, progesterone alone appears to have the greatest utility (area under the receiver operator characteristic curve = 0.923). Among dual-biomarker strategies, progesterone plus hCG and progesterone plus inhibin A improved specificity but not sensitivity. At 95% sensitivity, the combination of progesterone and hCG improved specificity from 0.29 to 0.66 (improvement = 0.37 [95% confidence interval 0.23, 0.52]). A triple-biomarker combination did not show substantial improvement over the dual-biomarker strategy. Also, combinations that used urine beta-core hCG did not improve diagnostic accuracy. CONCLUSION: Serum progesterone appeared to be the single most specific biomarker for distinguishing viable from nonviable pregnancies. When a dual-biomarker strategy was applied, combining serum progesterone with hCG, specificity improved significantly, which suggests that a multiple biomarker strategy might help distinguish viable from nonviable pregnancies in early gestation.

Hierarchical logistic regression models for clustered binary outcomes in studies of IVF-ET.

OBJECTIVE: To describe a hierarchical logistic regression model for clustered binary data, apply it to data from a study on the effect of hydrosalpinx on embryo implantation, and compare the results with analyses that do not account for clustering. DESIGN: Observational study. SETTING: Academic research environment. PATIENT(S): Women undergoing IVF-ET for tubal disease. MAIN OUTCOME MEASURE(S): Odds of per embryo implantation. RESULT(S): Although regression estimates are largely similar between the models, the hierarchical model properly reflects the added variation due to clustering. Standard errors are higher, confidence intervals are wider, and P values indicate fewer "statistically significant" effects. CONCLUSION(S): Ignoring important sources of variation in any analysis can lead to incorrect confidence intervals and P values. In studies of IVF-ET, where clustered data are common, unexplained heterogeneity can be substantial. In this setting, hierarchical logistic regression is an appropriate alternative to standard logistic regression.

Positive cone biopsy specimen margins in women infected with the human immunodeficiency virus.

OBJECTIVES: The purpose of this study was to compare the positive margin rate associated with cervical conization among women who are seropositive for human immunodeficiency virus with that among women who are seronegative. STUDY DESIGN: This was a cross-sectional study of 245 women who underwent cervical conization for the following indications: biopsy-proven cervical intraepithelial neoplasia grade 2 or 3, abnormal endocervical curettage specimen, cytologic-histologic examination discrepancy, persistent cervical intraepithelial neoplasia grade 1, or abnormal cytologic characteristics with inadequate colposcopic examination. RESULTS: Twenty-two (47.8%) of 46 women who were seropositive for human immunodeficiency virus and 65 (32.7%) of 199 women who were seronegative had positive cone biopsy specimen margins. In a multivariable logistic regression the human immunodeficiency virus-seropositive women had a 2-fold increased risk of having a positive cone biopsy margin (odds ratio, 2.25; 95% confidence interval, 1.07-4.76). CONCLUSION: If the presence of positive cone biopsy specimen margins represents the potential for disease progression, then our findings of a positive margin rate of nearly 50% in a human immunodeficiency virus-positive population may argue against the kind of conservative management of colposcopic follow-up that has been proposed for immunocompetent women.

Prevalence of lower genital tract infections among human immunodeficiency virus (HIV)-seropositive and high-risk HIV-seronegative women. HIV Epidemiology Research Study Group.

This study was undertaken to assess whether the prevalence of lower genital tract infections among human immunodeficiency virus (HIV)-seropositive women was higher than among high-risk HIV-seronegative women at their baseline visit for the HIV Epidemiology Research Study. Results were available for 851 HIV-seropositive and 434 HIV-seronegative women. Human papilloma virus (HPV) infection was more prevalent among HIV-seropositive women (64% vs. 28%). Bacterial vaginosis was common (35% vs. 33%), followed by trichomoniasis (12% vs. 10%), syphilis (8% vs. 6%), Chlamydia trachomatis infection (4% vs. 5%), candidal vaginitis (3% vs. 2%), and Neisseria gonorrhoeae infection (0.8% vs. 0.3%). Alcohol use (odds ratio [OR], 1.8; 95% confidence interval [CI], 1. 3-2.4) and smoking (OR, 1.8; 95% CI, 1.3-2.5) were associated with bacterial vaginosis. Bacterial vaginosis (OR, 2.3; 95% CI, 1.5-3.4), trichomoniasis (OR, 2.3; 95% CI, 1.1-4.7), and syphilis (OR, 3.1; 95% CI, 1.3-7.4) were found to be more prevalent among black women. Our study showed no statistically significant difference in the prevalence of lower genital tract infections except for HPV between HIV-infected and demographically and behaviorally similar HIV-uninfected high-risk women.

Self-reported bacterial infections among women with or at risk for human immunodeficiency virus infection.

Bacterial infections are a major cause of morbidity and mortality in persons with human immunodeficiency virus (HIV) infection, particularly women. We performed a cross-sectional analysis of a history of bacterial infections among 1,310 women with or at risk for HIV infection. HIV-seropositive women were significantly more likely than seronegative women to report recent and lifetime histories of bacterial infection, even after history of injection drug use since 1977 was adjusted for; this included recent pneumonia (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.5-6.6), sinusitis (OR, 1.4; 95% CI, 1.0-2.0), and urinary tract infection (OR, 1.5; 95% CI, 1.1-2.1). Compared with HIV-negative women, women with CD4 cell counts of <200 were about eight times more likely to report recent pneumonia (OR, 7.8; 95% CI, 3.4-17.7); those with CD4 cell counts of 200-500 were almost three times more likely to do so (OR, 2.6; CI, 1.2-5.7). Logistic regression analysis revealed that only CD4 cell category and a recent history of smoking had a significant relationship to self-reported pneumonia.

Influence of chorioamnionitis on developmental outcome in very low birth weight infants.

OBJECTIVE: To determine the effect of exposure to chorioamnionitis on developmental outcome in very low birth weight (VLBW) infants. METHODS: Five hundred four maternal charts (97% of all VLBW infants delivered from 1990 to 1994) were reviewed. A historical cohort study of the 330 infants delivered secondary to preterm premature rupture of membranes or preterm labor was performed. Case subjects (71) were delivered of mothers with chorioamnionitis by clinical criteria; control subjects (259) were delivered of mothers without chorioamnionitis. Bayley index scores at 7 months' corrected age and special care nursery outcomes were compared. One hundred seventy-three subjects were necessary to reject the two-sided null hypothesis with 80% power with a difference in mean Bayley index scores of at least 8. RESULTS: Neonatal sepsis (8.5% compared with 1.9%; odds ratio [OR] = 4.7, 95% confidence interval [CI] 1.4, 15.9, P = .015) and a low 5-minute Apgar (72% compared with 55%; OR = 2.1, CI 1.2, 3.8, P = .012) occurred more frequently in the chorioamnionitis group. One hundred eighty-seven (68%) of 273 surviving neonates had follow-up. Cases and controls were similar in mean Bayley mental developmental index (91.2 compared with 91.8, P = .84), Bayley psychomotor developmental index (89.8 compared with 89.1, P = .82), and number of infants developmentally delayed. Duration of exposure to chorioamnionitis did not affect neonatal outcome. CONCLUSION: Despite higher rates of sepsis and low Apgar scores, no difference in outcome at 7 months of corrected age was detected in VLBW infants exposed to chorioamnionitis. Contemporary neonatal management may reduce the adverse effects of this exposure.

Strength of indication for cesarean delivery: comparison of private physician versus resident service labor management.

OBJECTIVE: Our purpose was to compare the strength of indication for cesarean delivery for 2 groups of patients who had undergone cesarean delivery-those treated by physicians in private or group practice and those treated by a clinic or resident service. STUDY DESIGN: From records of 119 cesarean deliveries performed in 1992, data concerning patient history, labor course and management, fetal monitor tracings, and indications for cesarean delivery were extracted, summarized, and presented to 3 reviewers. Each reviewer rated the strength of indication for cesarean delivery on a 10-point visual analog scale and specified how often they would have chosen an alternative management plan. Reviewers were blinded to the research hypothesis and to patient age, type of provider, and insurance status. RESULTS: Using a multivariate linear regression model to adjust for differences in age and indication for cesarean delivery, we found that strength of indication scores were higher among patients treated by a resident service than among those treated by private physicians (P <.0001) and that an alternative action plan was more often suggested for deliveries managed by private physicians (P <.0001). CONCLUSIONS: Among women who underwent cesarean delivery, the strength of indication judged by a panel of reviewers not involved with the patient's care was stronger among resident-treated patients than among cases treated by private physicians. Although there are several possible explanations, the findings may suggest that physicians in private practice use different criteria than do resident physicians for deciding to perform a cesarean.

Age and the role of symptomatology in readiness to quit smoking.

To develop effective age-appropriate strategies for smoking cessation, it is important to understand factors associated with readiness to quit smoking. This article presents results from an analysis of the role of symptomatology in the decisions to quit smoking among three age groups (18-34, 35-54, and > or = 55 years) from a larger sample of smokers in a managed-care setting. Two measures of readiness to quit smoking were used: stages of change and intention to stop. Using ordinal logistic regression, we found that smokers in the middle and oldest age groups who had experienced at least three of five symptoms in the previous 2 weeks were more likely to be in higher stages of readiness. Regardless of age, smokers who attributed symptoms to smoking were more motivated to try to quit, whereas those who attributed symptoms to aging were less likely to intend to stop smoking. Findings from this study indicate a symptom-based approach to smoking cessation may be a useful strategy, especially in provider-based interventions.

The effect of a Medicaid managed care program on the adequacy of prenatal care utilization in Rhode Island.

OBJECTIVES: The purpose of this study was to determine whether adequacy of prenatal care utilization improved after the implementation of a Medicaid managed care program in Rhode Island. METHODS: Rhode Island birth certificate data (1993-1995; n = 37021) were used to analyze pre- and post-program implementation changes in adequacy of prenatal care utilization. Logistic regression models were used to characterize the variation in prenatal care adequacy as a function of both time and the various covariates. RESULTS: Adequacy of prenatal care utilization for Medicaid patients improved significantly after implementation of the program, from 57.1% to 62.1% (odds ratio [OR] = 1.2, 95% confidence interval [CI] = 1.1, 1.3). After the program was implemented, Medicaid patients who went to private physicians' offices for prenatal care were 1.4 times as likely as before to receive adequate prenatal care (OR = 1.4, 95% CI = 1.2, 1.7). CONCLUSIONS: Unlike many other Medicaid expansions for pregnant women, the RIte Care program in Rhode Island has resulted in significant improvement in adequacy of prenatal care utilization for its enrollees. This improvement was due to specific program interventions that addressed and changed organizational and delivery system barriers to care.

The effect of posterior wall support defects on urodynamic indices in stress urinary incontinence.

OBJECTIVE: To determine if posterior vaginal wall defects affect urodynamic indices and mask stress urinary incontinence. METHODS: Ninety women with grade 0, 1, 2, or 3 posterior wall defects were evaluated prospectively by complete urodynamics to assess their urinary complaints. None had severe anterior or apical support defects. Urethral pressure profilometry and cough stress test were performed with the posterior wall in the unretracted position and then with the posterior wall retracted using a split speculum. Analysis of covariance was used to compare adjusted mean differences in maximum urethral closure pressure, functional urethral length, and units of leakage volume during the cough stress test in the unretracted and retracted positions among the posterior wall grade groups. RESULTS: In women with grade 3 posterior wall defects, there were significant changes from the unretracted to the retracted position in maximum urethral closure pressure of -7.0 cm H20, (99% confidence interval [CI] -12.4, -1.6), functional urethral length of -0.3 cm (99% CI -0.5, -0.1), and leak volume units of +0.7 (99% CI 0.4, 1.0) during the cough stress test. There were four women with grade 3 posterior wall defects who demonstrated potential stress incontinence when their posterior wall was retracted. CONCLUSION: A grade 3 posterior wall defect may artificially raise maximum urethral closure pressure, increase functional urethral length, and mask urinary stress incontinence during a cough stress test. Women with grade 3 posterior wall defects should be tested with the posterior wall retracted during urodynamic evaluation.