Representation of Minority Groups in Key Pelvic Floor Disorder Trials.

BACKGROUND: Multicenter randomized clinical trials on pelvic floor disorders (PFDs) support evidence-based care. However, many of these studies include homogenous study populations lacking diversity. Heterogeneous sampling allows for greater generalizability while increasing knowledge regarding specific subgroups. The racial/ethnic makeup of key pelvic floor disorder (PFD) trials has not been examined. OBJECTIVE: This study aimed to investigate racial/ethnic representation in major PFD clinical trials in comparison to racial/ethnic distribution of PFD in the National Health and Nutritional Examination Survey (NHANES). METHODS: Demographic data were extracted from completed PFD Network (PFDN) and Urinary Incontinence Treatment Network studies, which have resulted in nearly 200 publications. Prevalence of PFD by race/ethnicity was obtained from the NHANES. A representative index (Observed "n" by PFD study/Expected "n" based on the NHANES-reported prevalence) was calculated as a measure of representation. Meta-analyses were performed for each outcome and overall with respect to race/ethnicity. RESULTS: Eighteen PFDN/Urinary Incontinence Treatment Network studies were analyzed. White women comprised 70%-89% of PFD literature; Black women, 6%-16%; Hispanic women, 9%-15%; Asians, 0.5%-6%; and American Indians, 0%-2%. Representation of White women was higher in 13 of 18 PFDN studies compared with the NHANES prevalence data. Representation of Black women was either decreased or not reported in 10 of 18 index studies compared with the NHANES prevalence data. Hispanic women were absent or underrepresented in 7 of 18 PFDN studies compared with the prevalence data. CONCLUSIONS: Our examination of PFDN and other landmark trials demonstrates inconsistent reporting of minority subgroups, limiting applicability with respect to minority populations. Our study suggests that PFD research would benefit from targeted sampling of minority groups.

Surgical treatment of detrusor underactivity: a short term proof of concept study

ABSTRACT Objectives To compare the surgical outcomes of men with bladder outlet obstruction (BOO) due to benign prostatic obstruction (BPO) to those with detrusor underactivity (DU) or acontractile detrusor (DA). Materials and Methods This retrospective, IRB approved study included men who underwent BPO surgery for refractory LUTS or urinary retention. Patients were grouped based on videourodynamic (VUDS) findings: 1) men with BOO, 2) men with DU and 3) men with DA. The primary outcome measure was the Patient Global Impression of Improvement (PGII). Secondary outcome measures included uroflow (Qmax), post-void residual volume (PVR) and the need for clean intermittent catheterization (CIC). Results One hundred and nineteen patients were evaluated: 1) 34 with BOO, 2) 62 with DU and 3) 23 with DA. Subjective success rate (PGII) was highest in the BOO group (97%) and those with DU (98%), while DA patients had a PGII success of 26%, (p<0.0001). After surgery, patients with BOO had the lowest PVR (68.5mL). Fifty-six patients (47%) performed CIC pre-operatively (47% of BOO, 32% of DU and 87% of DA patients). None of the patients in the BOO and DU groups required CIC post operatively compared to16/23 (69%) of patients in the DA group (p<0.0001). Conclusions BPO surgery is a viable treatment option in men with presumed BOO and DU while DA is a poor prognostic sign in men who do not void spontaneously pre-operatively.

Urogynecological conditions associated with overactive bladder symptoms in women.

INTRODUCTION: Overactive bladder symptoms (OAB) affect 9-43% of women and are associated with underlying disorders, including pelvic organ prolapse (POP) and stress urinary incontinence (SUI). The aim of this study is to identify urogynecological conditions associated with OAB symptoms. METHODS: This prospective, institutional review board-approved study included women referred to a tertiary centre with lower urinary tract symptoms (LUTS). All women completed the self-administered OAB questionnaire (OABSS). Those with an OABSS ≥8, the cutoff, were considered to have OAB symptoms. Patients underwent a history and physical examination (including Baden-Walker prolapse grading and stress test), 24-hour voiding diary, pad test (for urinary incontinence), urinalysis, and uroflow with post-void residual volume. Patients were classified clinically into the following: idiopathic OAB, SUI, POP, bladder outlet obstruction (BOO) neurogenic bladder (NGB), recurrent urinary tract infection (UTI), and miscellaneous. RESULTS: In total, 148 women met the inclusion criteria with a mean age of 67 years. Only 27% had no comorbid conditions and were considered idiopathic OAB. Associated urogynecological conditions included SUI in 37%, POP in 26%, miscellaneous conditions in 18%, recurrent UTI in 11%, NGB in 9%, and BOO in 8%. Some patients met criteria for more than one category, thus the total is greater than 100%. CONCLUSIONS: In a tertiary care setting, a significant proportion of women with OAB symptoms have underlying conditions that may cause or contribute to their symptoms. Appropriate evaluation is desirable to enhance our understanding of the relationship of these conditions to the diagnosis, treatment, outcomes, and pathophysiology of OAB.

Surgical treatment of detrusor underactivity: a short term proof of concept study.

OBJECTIVES: To compare the surgical outcomes of men with bladder outlet obstruction (BOO) due to benign prostatic obstruction (BPO) to those with detrusor underactivity (DU) or acontractile detrusor (DA). MATERIALS AND METHODS: This retrospective, IRB approved study included men who underwent BPO surgery for refractory LUTS or urinary retention. Patients were grouped based on videourodynamic (VUDS) findings: 1) men with BOO, 2) men with DU and 3) men with DA. The primary outcome measure was the Patient Global Impression of Improvement (PGII). Secondary outcome measures included uroflow (Qmax), post-void residual volume (PVR) and the need for clean intermittent catheterization (CIC). RESULTS: One hundred and nineteen patients were evaluated: 1) 34 with BOO, 2) 62 with DU and 3) 23 with DA. Subjective success rate (PGII) was highest in the BOO group (97%) and those with DU (98%), while DA patients had a PGII success of 26%, (p<0.0001). After surgery, patients with BOO had the lowest PVR (68.5mL). Fifty-six patients (47%) performed CIC pre-operatively (47% of BOO, 32% of DU and 87% of DA patients). None of the patients in the BOO and DU groups required CIC post operatively compared to16/23 (69%) of patients in the DA group (p<0.0001). CONCLUSIONS: BPO surgery is a viable treatment option in men with presumed BOO and DU while DA is a poor prognostic sign in men who do not void spontaneously pre-operatively.

A positive feedback mechanism that regulates expression of miR-9 during neurogenesis.

MiR-9, a neuron-specific miRNA, is an important regulator of neurogenesis. In this study we identify how miR-9 is regulated during early differentiation from a neural stem-like cell. We utilized two immortalized rat precursor clones, one committed to neurogenesis (L2.2) and another capable of producing both neurons and non-neuronal cells (L2.3), to reproducibly study early neurogenesis. Exogenous miR-9 is capable of increasing neurogenesis from L2.3 cells. Only one of three genomic loci capable of encoding miR-9 was regulated during neurogenesis and the promoter region of this locus contains sufficient functional elements to drive expression of a luciferase reporter in a developmentally regulated pattern. Furthermore, among a large number of potential regulatory sites encoded in this sequence, Mef2 stood out because of its known pro-neuronal role. Of four Mef2 paralogs, we found only Mef2C mRNA was regulated during neurogenesis. Removal of predicted Mef2 binding sites or knockdown of Mef2C expression reduced miR-9-2 promoter activity. Finally, the mRNA encoding the Mef2C binding partner HDAC4 was shown to be targeted by miR-9. Since HDAC4 protein could be co-immunoprecipitated with Mef2C protein or with genomic Mef2 binding sequences, we conclude that miR-9 regulation is mediated, at least in part, by Mef2C binding but that expressed miR-9 has the capacity to reduce inhibitory HDAC4, stabilizing its own expression in a positive feedback mechanism.