Urodynamics as a Prognosticator of Mirabegron Treatment Outcomes.

AIMS: To determine if findings at urodynamics prognosticate improvements in overactive bladder symptoms among women receiving mirabegron treatment. METHODS: Before treatment, women completed a urodynamic investigation, a micturition diary and the Urinary Distress Inventory (UDI) with the irritative subscale UDIOAB. After 6 months mirabegron treatment, patients were clinically evaluated and completed the UDI. Associations were tested using regression analyses and nonparametric statistics. RESULTS: Testing urodynamic variables for association with treatment effects in multiple linear regression analysis showed that lower volumes at first sensation to void significantly correlated with greater improvement in the UDIOAB after 6 months mirabegron treatment (B = 0.026, 95% CI 0.002-0.049, p = 0.034). Improvements in UDIOAB showed no correlation with presence of nocturia (p = 0.65), previous use of anticholinergics (p = 1), menopausal status (p = 1), any detrusor overactivity during filling (p = 1), phasic detrusor contractions during filling (p = 1), or detrusor overactivity during inhibition (p = 1). CONCLUSIONS: We found limited support for clinically relevant associations between findings at urodynamics and subsequent treatment outcomes for mirabegron in routine clinical practice. Our findings do not support the role of these investigations as predictors of outcomes in patients with overactive bladder symptoms.

Clinical practice of BOTOX® treatment for overactive bladder syndrome in Sweden: an assessment of resource use and external validity.

OBJECTIVE: The objective of this study was to assess the resource use of treating overactive bladder (OAB) patients in real-world clinical practice and to evaluate whether there is external validity in the treatment of OAB in clinical practice. MATERIALS AND METHODS: The study included 55 patients suffering from OAB and treated with BOTOX® at two Swedish clinics. The study was conducted as an anonymized retrospective chart review study. RESULTS: The estimated yearly direct cost of BOTOX treatment was €902. The mean age of patients in the study was 60 years, and 85% were women. The severity of OAB before BOTOX treatment, given by the mean number of daily leakages, equalled 4.8. The median interval between treatments was 210 days. CONCLUSIONS: Patient characteristics in the real world were similar to those in the clinical trials, showing a high degree of external validity. Treatment intervals were longer in the real world than in clinical trials, indicating that treatment cost could be lower when patients are treated as observed in real-world clinical practice.

Twenty-Four-Hour Voiding Diaries Versus 3-Day Voiding Diaries: A Clinical Comparison.

OBJECTIVE: This study aimed to determine if 24-hour versus 3-day voiding diary affects medical decision making for women with urinary incontinence. METHODS: A retrospective chart review was conducted of patients presenting to the OhioHealth Urogynecology Physician group for urinary incontinence from 2009 to 2011. Practice protocol includes patient completion of a 3-day voiding diary before their appointment. Diagnostic and treatment plans were extracted based on the initial patient encounter and 3-day voiding diary. A chart review was then completed with the first 24 hours of the same diaries, principal history, and physical examination data compiled into a separate chart. These charts were then reevaluated by the same physician who initially provided care to the patient but were blinded to their previous orders, impressions, and plans. New plans were then created based on the 24-hour diaries and compared with the original plans. RESULTS: One hundred eighty-six charts were reviewed. There was good agreement between 24-hour and 3-day diaries in recommendations for first-line behavioral modifications (Κ > 0.6) and moderate agreement between diaries in initiation of medical therapy or trial of incontinence pessary (Κ > 0.4). However, 24-hour diaries resulted in a statistically significant increase in invasive diagnostic tests (P < 0.019) and other treatment recommendations when compared with 3-day diaries. CONCLUSIONS: Use of 24-hour diaries may result in increased testing when compared with 3-day diaries. It may be prudent to postpone invasive testing in those patients who initially are noncompliant with a longer diary until a more complete history can be obtained.

Hormonal influence on the effect of mirabegron treatment for overactive bladder.

OBJECTIVE: The aim of this study was to evaluate if levels of gonadotropic and sex steroidal hormones influence the efficacy of mirabegron in the treatment of overactive bladder. METHODS: We included 58 female participants who received treatment with mirabegron 50 mg once daily and provided a blood sample for hormone profiling before treatment was initiated. Serum hormone concentrations for estradiol, progesterone, testosterone, FSH, LH, TSH, and T4 were analyzed. Urinary Distress Inventory (UDI), (overactive bladder domain: UDIOAB), and the short form Pelvic Floor Impact Questionnaire (PFIQ-7) were used to assess subjective outcomes. RESULTS: There were significant overall improvements in UDI, UDIOAB, and the PFIQ from baseline to the 2 months of follow-up (P = 0.001, 0.001, and 0.008, respectively). The magnitude of the mean difference of improvements was similar between pre- and postmenopausal women. Estrogen levels were nonsignificantly lower in participants who experienced an improvement in UDI and UDIOAB at 2 months of follow-up as compared with those that did not (P = 0.7). There were no other clinically relevant differences in hormone levels in relation to improvements in UDI, UDIOAB, or PFIQ. In logistic regression analysis there were no associations between UDIOAB outcomes and age, previous use of anticholinergic drugs, parity, menopause, and local estrogen treatment. CONCLUSIONS: Estradiol, gonadotropic hormones, thyroid hormones, and testosterone levels did not influence the clinical effects of mirabegron in women with overactive bladder. Menopause status should not be a determinant for mirabegron treatment.

Safety and efficacy of mirabegron in daily clinical practice: a prospective observational study.

OBJECTIVE: To determine risks associated with prescribing mirabegron, the first-in-class ß3-adrenoreceptor agonist, to non-selected female patients with overactive bladder. STUDY DESIGN: Routine female patients seeking treatment for overactive bladder (n=221) in a urology/gynecology outpatient clinic. Data on adverse events, cardiovascular outcomes, condition specific symptoms and drug discontinuation was collected at two months follow-up (FU). Non-parametric statistics was used as appropriate. Odds ratios (ORs) with 95% confidence intervals (CIs) for outcome association analyses using logistic regression. RESULTS: 16 patients (7.2%) discontinued treatment because of side effects. There were no significant associations between cardiovascular adverse events and pre-existing cardiovascular disease (OR 0.3, 95% CI 0.3-2.6), or pre-existing ECG abnormalities (OR 2.3, 95% CI 0.3-16.3). At FU ECGs there were no de novo cases of tachyarrhythmias and no significant difference in mean QTc between baseline (403ms, SD 21.7) and the 2 months follow-up ECG (403ms, SD 20.3) (p=0.75). There was a significant decrease in the mean systolic blood pressure (p=0.03) but no significant change in mean diastolic pressure (p=0.8) or heart rates (p=0.2) from baseline to FU. Overactive bladder specific symptoms and quality of life improved significantly (p<0.001 respectively). CONCLUSIONS: Mirabegron treatment is associated with a satisfactory cardiovascular safety profile, as well as, significant symptomatic improvement also in a heterogeneous population of non-selected women with overactive bladder presenting in everyday clinical practice.

Mycoplasmataceae Colonizations in Women With Urethral Pain Syndrome: A Case-Control Study.

OBJECTIVES: To determine if Mycoplasma genitalium, Ureaplasma urealyticum, and Ureaplasma parvum are more common in premenopausal women with urethral pain syndrome than in asymptomatic controls. METHODS: We used a case-control study design to compare the prevalence of M. genitalium, U. urealyticum, and U. parvum using polymerase chain reaction (PCR) analysis in urine. Urethral pain syndrome was defined as localized urethral pain with or without accompanying lower urinary tract symptoms during the past month or longer and at least one negative urine culture. RESULTS: Among the 28 cases, 46% carried Ureaplasma species compared with 64% of the 92 controls overall (P = 0.09). There were no significant differences in the prevalence of U. parvum and U. urealyticum among controls than in patients with urethral pain syndrome (P = 0.35 and P = 0.33, respectively). Co-colonization with U. parvum and urealyticum was infrequent, and there was only one case of M. genitalium colonization, which occurred among the controls. The symptomatic profile of Ureaplasma carriers with urethral pain syndrome was heterogeneous with no clear pattern and did not differ significantly compared with patients negative for Ureaplasma. CONCLUSIONS: We found no evidence to support the notion that M. genitalium, U. parvum, and U. urealyticum are more prevalent in women with urethral pain syndrome than in women without lower urinary tract symptoms.

Risk factors for mesh complications after trocar guided transvaginal mesh kit repair of anterior vaginal wall prolapse.

AIMS: To identify risk factors for mesh exposures after anterior pelvic organ prolapse repair using a standardized trocar guided polypropylene mesh kit. METHODS: A secondary risk analysis combining patients from two prospective multicenter studies. Main outcome was clinical host-vs-implant reactions one year after surgery using a macroscopic inflammatory scale. RESULTS: 353 patients were included in the study. Mean age at surgery was 65.3 (± 9.6 SD) years and surgery was performed as a primary procedure in 224/353 (63.5%) patients. Mesh exposures, of which the majority were mild-moderate, occurred in a total of 30/349 patients (8.6%). Multivariate logistic regression showed increased odds for mesh exposures for women who smoked before surgery (OR 3.48, 95% CI 1.18-10.28), who had given birth to more than two children (OR 2.64, 95% CI 1.07-6.51) and those with somatic inflammatory disease (OR 5.11, 95% CI 1.17-22.23). Age, body mass index, and menopausal status showed no significant association with clinical mesh exposures. CONCLUSIONS: Smoking, multiple childbirth, and somatic inflammatory disease are possible risk factors for mesh exposure after trocar guided mesh kit surgery for anterior pelvic organ prolapse. Preoperative smoking cessation may decrease the risk for exposures.

Histological inflammatory response to transvaginal polypropylene mesh for pelvic reconstructive surgery.

PURPOSE: We prospectively evaluated the histological inflammatory response to the large polypropylene transvaginal mesh used for pelvic organ prolapse surgery. MATERIALS AND METHODS: Ten patients and 8 controls underwent vaginal punch biopsy sampling before surgery and patients also underwent it 1 year after pelvic reconstructive surgery using polypropylene mesh. Foreign body response to the mesh was assessed using a combination of histological, semiquantitative and computerized image based analysis. RESULTS: Compared to preoperative histology there was a significant postoperative increase in macrophage and mast cell counts (p = 0.03 and 0.01) but no significant changes in the count of cells involved primarily in the infectious cell response or collagen density and the elastin area fraction at the mesh-tissue interface (p = 0.2 and 0.3, respectively). Three cases of mild granuloma formation and 2 of mild erosion were observed. There was no significant change in epithelial thickness when comparing preoperative and postoperative samples. CONCLUSIONS: When used for pelvic reconstructive surgery, macroporous monofilament polypropylene mesh induces a mild but persistent foreign body reaction.

Trocar-guided transvaginal mesh repair of pelvic organ prolapse.

OBJECTIVE: To prospectively assess clinical outcomes after pelvic organ prolapse repair with a standardized trocar-guided surgical device using polypropylene mesh. METHODS: This was a prospective multicenter cohort study performed throughout 26 clinics. Evaluation at baseline, 2 months, and 1 year after surgery included prolapse grading using the pelvic organ prolapse quantification system (POP-Q) and symptom assessment using the Incontinence Impact Questionnaire (IIQ-7) and Urogenital Distress Inventory (UDI-6). For the purpose of this study, postoperative POP-Q stage 0-I was considered anatomic cure. RESULTS: Two-hundred sixty-one patients were included in the study; 232 (89%) attended the 1-year follow-up. Mean+/-standard deviation age at surgery was 66.3+/-9.4 years. Anatomic cure 1 year after surgery was observed in 96 of 121 women (79%) after anterior repair with mesh (P<.001), and 56 of 68 (82%) after posterior repair with mesh (P<.001). For combined anterior and posterior mesh repair, cure was 51 of 63 (81%) and 54 of 63 (86%) for the anterior and posterior compartment, respectively (P<.001 for both). Bladder and rectal perforations occurred in 9 of 252 patients (3.4%). Vaginal erosions, the majority mild to moderate, occurred in 26 of 232 cases (11%). Surgical intervention due to mesh exposure occurred in seven cases (2.8%). There were significant quality-of-life improvements in all domains of the IIQ-7. Despite significant improvements in UDI-6 scores, symptoms specific for stress urinary incontinence were not ameliorated. CONCLUSION: Trocar-guided transvaginal mesh surgery for pelvic organ prolapse is associated with satisfactory objective and subjective outcomes 1 year after surgery. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00402844 LEVEL OF EVIDENCE: II.

Sexual dysfunction after trocar-guided transvaginal mesh repair of pelvic organ prolapse.

OBJECTIVE: To estimate sexual dysfunction before and after trocar-guided transvaginal mesh surgery for pelvic organ prolapse. METHODS: Sexually active women participating in a prospective multicenter study were recruited at 26 centers. All participants underwent a standardized surgical procedure and were evaluated before (n=105) and 1 year after (n=84) surgery using the short form of the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12). Nonparametric statistics were used for comparisons. RESULTS: Mean age at surgery was 61.5 years (standard deviation [SD] 7.6), median parity was 2 (range, 1-6), and mean body mass index was 26.8 (SD 4.3) (body mass index is calculated as weight (kg)/[height m]). Anterior transvaginal mesh repair was performed in 46 patients (44%), posterior in 26 patients (25%), and combined anterior and posterior in 33 patients (31%). Overall sexual function scores worsened from 15.5 (SD 8.0) at baseline to 11.7 (SD 6.9) 1 year after surgery (P<.001). The trend toward deteriorating sexual function scores was similar for all three surgical procedures. There was an overall worsening of all symptoms in the behavioral-emotive and partner-related items, whereas improvements were observed in physical function. Overall rates and severity of dyspareunia in specific neither improved nor worsened. CONCLUSION: Sexual function scores deteriorate 1 year after trocar-guided transvaginal mesh surgery. The worsening was attributed primarily to a worsening in behavioral-emotive and partner-related items. Anatomical cure after surgery was not associated with improved PISQ scores. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00402844 LEVEL OF EVIDENCE: II.