Reduced versus standard intradetrusor OnabotulinumtoxinA injections for treatment of overactive bladder.

BACKGROUND: Intradetrusor onabotulinumtoxinA injection is an effective advanced treatment for overactive bladder. While the effective dosages have been well studied, very little data exist on treatment efficacy using differing injection techniques. The objective of this study was to determine whether the efficacy of a reduced injection technique of 5 injection sites was noninferior to the standard technique of 20 injection sites of intradetrusor onabotulinumtoxinA for treatment of overactive bladder. METHODS: In this randomized noninferiority trial, men and women seeking treatment of overactive bladder with intradetrusor onabotulinumtoxinA injections were randomized to receive 100 units administered via either a reduced injection technique of 5 injection sites or a standard injection technique of 20 injection sites. Subjects completed a series of standardized questionnaires at baseline and at 4-12 weeks postprocedure to determine symptom severity and treatment efficacy. The primary outcome was treatment efficacy as determined by Overactive Bladder Questionnaire-Short Form with a noninferiority margin of 15 points. Secondary outcomes were incidence of urinary tract infection and urinary retention requiring catheterization. RESULTS: Data from 77 subjects were available for analysis with 39 in the control arm (20 injections) and 38 in the study arm (5 injections). There was a significant improvement in both arms from baseline to follow-up in Overactive Bladder Questionnaire-Short Form and International Consultation on Incontinence Questionnaire scores (p < 0.001). Overall treatment success was 68% with no statistically significant difference between arms. A significant difference between arms was found on the Overactive Bladder Questionnaire-Short Form quality of life survey favoring the control arm (confidence interval [CI]: 0.36-20.5, p = 0.04). However, there were no significant differences between arms in the remaining validated questionnaires. The study arm did not demonstrate noninferiority to the control arm. Subjects in the study arm were significantly more likely to express a willingness to undergo the procedure again (odds ratio = 3.8, 95% CI: 1.42-10.67, p = 0.004). Adverse events did not differ between arms. CONCLUSIONS: A reduced injection technique for administration of intradetrusor onabotulinumtoxinA demonstrates similar efficacy to the standard injection technique but did not demonstrate noninferiority. Subjects preferred the reduced injection technique over the standard technique. A reduced injection technique is a safe and effective alternative to the standard technique.

The Impact of Pallidal and Subthalamic Deep Brain Stimulation on Urologic Function in Parkinson's Disease.

OBJECTIVE: Deep Brain Stimulation (DBS) is an established adjunctive surgical intervention for treating Parkinson's disease (PD) motor symptoms. Both surgical targets, the globus pallidus interna (GPi) and subthalamic nucleus (STN), appear equally beneficial when treating motor symptoms but effects on nonmotor symptoms are not clear. Lower urinary tract symptoms (LUTS) are a common PD complaint. Given prior data in STN-DBS, we aimed to further explore potential benefits in LUTS in both targets. METHODS: We performed a prospective, nonblinded clinical trial evaluating LUTS in PD patients in both targets pre and post DBS using validated urologic surveys. Participants were already slated for DBS and target selection predetermined before study entry. LUTS was evaluated using: the American Urological Association (AUA-SI), Quality of Life score (QOL), Overactive Bladder 8 Questionnaire (OAB-q), and Sexual Health Inventory for Men (SHIM). RESULTS: Of 33 participants, 20 underwent STN DBS and 13 had GPi DBS. Patients demonstrated moderate baseline LUTS. The urologic QOL score significantly improved post DBS (3.24 ± 1.77vs. 2.52 ± 1.30; p = 0.03). Analyzed by target, only the STN showed significant change in QOL (3.20 ± 1.61 vs 2.25 ± 1.33; p = 0.04). There were no other significant differences in urologic scores post DBS noted in either target. CONCLUSION: In PD patients with moderate LUTS, there were notable improvements in QOL for LUTS post DBS in the total sample and STN target. There may be differences in DBS effects on LUTS between targets but this will require further larger, blinded studies.

Contemporary comparison between retropubic midurethral sling and autologous pubovaginal sling for stress urinary incontinence after the FDA advisory notification.

OBJECTIVE: To compare the efficacy and safety in a contemporary cohort of women who were offered either a pubovaginal sling (PVS) or a synthetic midurethral sling (MUS) after the U.S. Food and Drug Administration notification and made an informed decision on procedure option. METHODS: A total of 201 women were given the option between a PVS and an MUS. Prior anti-incontinence surgery and concomitant surgery other than hysterectomy were not allowed. Minimal follow-up was 12 months. Patients were prospectively followed with validated quality of life questionnaires. Cure, voiding complaints, and complications were compared between the groups. RESULTS: Ninety-one women (45%) underwent PVS and 110 underwent MUS (55%). Median follow-up was 13.8 months. There was no difference in baseline characteristics between the groups except for the prevalence of urge incontinence. Subjective improvement in questionnaire scores was significant for both groups. Cure rate was accomplished in 75.8% of the PVS group patients compared with 80.9% of the MUS group patients (hazard ratio, 1.35; 95% confidence interval, 0.69-2.7; P = .38). Complications and voiding difficulty were similar between the groups. CONCLUSION: In this contemporary cohort of women considered suitable candidates for either a PVS or an MUS, both offer comparable efficacy and complication rates. PVS may be safely offered to patients who would otherwise be good candidates for MUS if they are concerned with the implantation of mesh.

Postoperative pain outcomes after transvaginal mesh revision.

INTRODUCTION AND HYPOTHESIS: Although the current literature discusses mesh complications including pain, as well as suggesting different techniques for removing mesh, there is little literature regarding pain outcomes after surgical removal or revision. The purpose of this study is to determine if surgical removal or revision of vaginal mesh improves patient's subjective complaints of pelvic pain associated with original placement of mesh. METHODS: After obtaining approval from the Vanderbilt University Medical Center Institutional Review Board, a retrospective review of female patients with pain secondary to previous mesh placement who underwent excision or revision of vaginal mesh from January 2000 to August 2012 was performed. Patient age, relevant medical history including menopause status, previous hysterectomy, smoking status, and presence of diabetes, fibromyalgia, interstitial cystitis, and chronic pelvic pain, was obtained. Patients' postoperative pain complaints were assessed. RESULTS: Of the 481 patients who underwent surgery for mesh revision, removal or urethrolysis, 233 patients met our inclusion criteria. One hundred and sixty-nine patients (73 %) reported that their pain improved, 19 (8 %) reported that their pain worsened, and 45 (19 %) reported that their pain remained unchanged after surgery. Prior history of chronic pelvic pain was associated with increased risk of failure of the procedure to relieve pain (OR 0.28, 95 % CI 0.12-0.64, p = 0.003). CONCLUSIONS: Excision or revision of vaginal mesh appears to be effective in improving patients' pain symptoms most of the time. Patients with a history of chronic pelvic pain are at an increased risk of no improvement or of worsening pain.

Discontinuation of antipsychotic medication in pregnancy: a cohort study.

BACKGROUND: Women prescribed antipsychotics face the dilemma on whether to continue medication in pregnancy in terms of balancing risks and benefits. Previous research on other psychotropic medications suggests that many women discontinue treatment in early pregnancy. However, very limited evidence exists on discontinuation of antipsychotic medication. METHODS: We identified 495,953 pregnant women from THIN primary care database. Kaplan-Meier plots were used to examine time to last antipsychotic prescription. Poisson regression was used to examine characteristics of those who stopped treatment during pregnancy. RESULTS: There has been an overall increase in prevalence of antipsychotic prescribing since 2007. However, antipsychotics were more likely to be stopped in pregnant than non-pregnant women. Only 107/279 (38%) of women on atypical antipsychotics and 39/207 (19%) of women on typical antipsychotics before pregnancy still received treatment at the start of third trimester. Older women were more likely to continue typical antipsychotic treatment in pregnancy (35+ versus <25 years risk ratio: 3.09 [95% CI 1.76, 5.44]). Likewise, those who received typical antipsychotics for longer periods before were most likely to continue treatment in pregnancy (12+ versus <6 months: RR: 3.12 [95% CI 1.97, 4.95]). For atypical antipsychotics length and dose of prior prescribing were also associated with continuation in pregnancy. CONCLUSIONS: Pregnancy was a major determinant of cessation of antipsychotics. Only 38% of women on atypical and 19% on typical antipsychotics were still prescribed the drug in the third trimester. Duration of prior treatment, maternal age as well as dose was significantly associated with continued treatment of antipsychotics in pregnancy.

The role of electrical stimulation techniques in the management of the male patient with urgency incontinence.

PURPOSE OF REVIEW: Overactive bladder affects 10-27% of men, a significant portion of whom report urge urinary incontinence that is inadequately treated with first-line and second-line treatments. There is thus a substantial need to critically evaluate the alternative means of clinical management. RECENT FINDINGS: This review presents the current evidence for the use of sacral neuromodulation and percutaneous tibial nerve stimulation in the treatment of men with urge incontinence, as well as evaluates the financial implications of these treatments. Other alternative modes of electrical stimulation for urge incontinence are also briefly reviewed. SUMMARY: Both sacral neuromodulation and percutaneous tibial nerve stimulation prove to be viable, durable options for treating patients with refractory urge incontinence. Alternative modes of stimulation are also beginning to show promise.

Analysis of patient and technical factors associated with midurethral sling mesh exposure and perforation.

OBJECTIVES: To evaluate the technical and patient characteristics associated with the development of mesh perforation and exposure in patients after midurethral sling surgeries. METHODS: After a retrospective review of referred patients, the risk of mesh perforation of the urinary tract over exposure in the vagina was analyzed with multivariate logistic regression, adjusting for the possible predictors of age, body mass index, smoking status at the time of mesh placement, presence of diabetes, type of sling placed, type of surgeon and trocar injury at the time of mesh placement. RESULTS: A total of 77 women were identified, 27 with mesh perforation and 50 with mesh exposure. The patients' average body mass index was 29.2, and 13% were diabetic. Nine (33%) patients in the perforation group and two (4%) patients in the exposure group had evidence of trocar injury to the bladder or urethra at the time of mesh placement (P < 0.001). After multivariate logistic regression analysis, trocar injury (odds ratio 25.90, 95% confidence interval 2.84-236.58, P = 0.004) and diabetes (odds ratio 9.90, 95% confidence interval 1.1.25-78.64, P = 0.03) were associated with an increased risk of mesh perforation. Increased body mass index (odds ratio 0.88, 95% confidence interval 0.77-0.99, P = 0.05) was associated with a decreased risk of mesh perforation. Finally, postoperative hematomas and blood transfusions occurred more commonly in the mesh perforation group (15% vs 0%, P = 0.01). CONCLUSIONS: Trocar injury, diabetes and bleeding complications at the time of surgery are associated with higher risk of mesh perforation in patients undergoing midurethral sling placement.

Vaginal approaches to pelvic organ prolapse repair.

PURPOSE OF REVIEW: Changes in perception regarding the safety of mesh require a review of vaginal approaches for pelvic organ prolapse surgery with and without mesh. The purpose of this article is to examine the implications of the negative stigma toward mesh and review the outcomes of different vaginal approaches to pelvic organ prolapse repair. RECENT FINDINGS: Defining a successful outcome of pelvic organ prolapse surgery from a symptomatic perspective instead of an anatomic perspective reveals that native tissue repairs and graft repairs are equivalent. In the posterior and apical compartments, a review of multiple studies shows that native tissue and graft transvaginal repairs have similar anatomic results except that native tissue repairs do not carry the risk of mesh extrusion. After failure of a native tissue repair, the majority of surgeons will use a graft-augmented repair. SUMMARY: Controversy exists about how to define a successful outcome after pelvic organ prolapse surgery. Native tissue repairs require a more individualized approach than mesh-augmented repairs because native tissue requires the surgeon to closely examine the patient to determine the exact compartment and location that is affected before deciding on a surgical approach.

Higher expression of the androgen-regulated gene PSA/HK3 mRNA in prostate cancer tissues predicts biochemical recurrence-free survival.

PURPOSE: Alterations of the androgen receptor (AR)-mediated signaling through numerous mechanisms are increasingly recognized in prostate cancer (CaP) progression. We hypothesized that the assessment of well-defined AR transcriptional targets (e.g., PSA/HK3 mRNA) in CaP tissues will provide in vivo readout of AR dysfunctions. Moreover, quantitative expression features of PSA/HK3 mRNA in prostate tumor cells may serve as a prognostic indicator of disease progression. EXPERIMENTAL DESIGN: Paired benign and malignant epithelial cells (242 specimens) were obtained from laser capture microdissection of frozen OCT-embedded tissue sections prepared from radical prostatectomy specimens of 121 patients. Quantitative expression of PSA/HK3 mRNA in the matched malignant and benign cells was analyzed by real-time reverse transcription-PCR. RESULTS: CaP cells express significantly lower PSA/HK3 mRNA levels than matched benign cells (P = 0.0133). Moreover, low PSA/HK3 mRNA expression in malignant cells was associated with increased risk of biochemical recurrence (P = 0.0217), as well as with time to recurrence (P = 0.0371), in patients with intermediate preoperative serum prostate-specific antigen levels (2-10 ng/mL). The expression of androgen-dependent genes in clinical samples correlates with each other in patients with higher expression of PSA/HK3 mRNA but not in patients with lower expression of PSA/HK3 mRNA reflecting AR pathway dysfunction. CONCLUSIONS: Our study has unraveled a novel prognostic utility of quantitative measurements of PSA/HK3 mRNA reflecting AR transcriptional activity in CaP cells, which is independent of serum prostate-specific antigen. It also has potential in stratifying subsets of patients exhibiting progressive disease associated with dampened AR transcriptional functions who may be targeted by tailored therapeutic strategies.