Faculty Bibliography

Background: Overactive bladder (OAB) is a chronic condition that can cause significant burden and have a negative effect on patients' daily lives. There is a need to offer patients with OAB who are inadequately managed by an anticholingergic alternative therapies that are effective and improve quality of life (QOL) over the long-term. A long-term extension study involving patients with OAB and urinary incontinence (UI) who were inadequately managed by an anticholinergic (ACH) demonstrated that onabotulinum toxin A 100U provides consistent, long-term improvement of OAB symptoms. Here we evaluated the long-term effects of onabotulinum toxin A 100U on QOL in this extension study. Methods: Eligible patients who completed either of two phase 3 trials could enter a three-year extension study to receive onabotulinum toxin A treatment "as needed" for control of symptoms. Results are reported for up to six treatments. Assessments included change from baseline in Incontinence-QOL (I-QOL) total score and proportions of patients who achieved/exceeded the minimally important difference (MID) in I-QOL score (+10 points) after each treatment. Consistency of response over repeat treatments was evaluated by determining whether patients achieved >=MID after the first treatment, and then analyzing the proportion who achieved >=MID for all subsequent treatments. Results: Of 829 patients enrolled, discontinuations due to lack of efficacy/ adverse events were 5.7%/5.1%. After onabotulinum toxin A treatments 1-6, QOL improvements were consistently maintained at 2-3X MID across treatment cycles, with most patients achieving >=MID (range 65.2-76.1%). 72.9% of patients who achieved >=MID after treatment 1 maintained I-QOL improvements >=MID in all subsequent treatments. Over one-third (38.3%) of patients not achieving >=MID after treatment 1 achieved improvements >=MID in all subsequent treatments. No new safety signals were observed. Conclusions: Consistent improvements in OAB symptoms after long-term treatment with onabotulinum toxin A corresponded with durable QOL improvements, with no new safety signals. Patients with clinically meaningful QOL improvements after treatment 1 had similar improvements in subsequent treatments, while lack of response to treatment 1 did not preclude positive response(s) in subsequent treatments. These results help set treatment expectations of patients and clinicians for onabotulinum toxin A and support persistence of its use over the long-term. Additional analyses may further characterize the long-term effects of treatment with onabotulinum toxin A in patients with OAB inadequately managed by an ACH

Background: Pharmacotherapy is the second-line treatment for overactive bladder (OAB) after behavioral therapy, but there is a high discontinuation rate due to inadequate efficacy and/or intolerable side effects. Onabotulinum toxin A provides an additional treatment option for OAB in patients who are inadequately managed by an anticholinergic. This is the first comparison of the efficacy of all licensed doses of anticholinergics, mirabegron, and onabotulinum toxin A vs. placebo in adults with idiopathic overactive bladder using network meta-analysis (NMA) and meta-regression (NMR). Methods: Electronic databases, review documents, guidelines, and websites were searched for randomized blinded trials of >=2 weeks duration comparing any dose of onabotulinum toxin A, mirabegron, or oral/ transdermal anticholinergics with each other or placebo. Networks were developed for outcomes of interest based on studies of similar quality of study methods, confounding factors, common treatment arms, and outcomes measured. Bayesian random effects NMA (for the outcome of 100% reduction in urinary incontinence episodes [UIE]) and NMR (for outcomes on changes from baseline in UIE, urgency episodes, and micturition frequency) models were used to synthesize results at Week 12. Safety outcomes were not compared due to differences in adverse event profiles. Results: One hundred two trials were assessed. NMRs indicated that, after adjusting for differences in baseline severity between trials, all treatments were more efficacious than placebo. Patients who received onabotulinum toxin A (100U) had the greatest mean reductions in UIE (1.55 episodes/ day more than placebo [95% credible interval (CrI) 1.10, 2.01]), urgency (2.01 episodes/day more than placebo [CrI 1.48, 2.54]) and micturition frequency (1.37 episodes/day more than placebo [CrI 1.03, 1.70]). Onabotulinum toxin A patients also had the highest likelihood of achieving 100% UIE reduction (OR 4.30 vs. placebo [CrI: 3.03, 6.23]). Conclusions: This analysis suggests that onabotulinum toxin A 100U provides the greatest reduction in OAB symptoms and higher likelihood of being dry, relative to placebo, than all licensed doses of anticholinergics and mirabegron in the network. Additional studies should also evaluate the cost-effectiveness of onabotulinum toxin A vs. other OAB treatments

BACKGROUND: Nocturia (interruption of sleep due to the need to urinate) affects an estimated 15% of men and 20% of women.
OBJECTIVE(S): To assess baseline data from a 1-year, prospective, observational study in order to estimate the humanistic and economic burden, including work productivity, healthcare resource utilization (HRU) and costs, associated with nocturia in adult patients.
METHOD(S): Adult patients enrolled in HealthCare Partners (HCP) Medical Group with nocturia for >= 6 months were recruited based on claims with ICD-9 codes for nocturia alone (788.43), or combined with overactive bladder (596.51) and/or benign prostatic hyperplasia (600.0x). Demographic, nocturia, and treatment history, as well as quality of life and work productivity data (using the EQ-5D and WPAI, respectively) were obtained through telephone, web-based, or in-clinic questionnaires. HRU (outpatient, emergency room [ER], hospital, and pharmacy utilization) and costs were identified from HCP claims in the 6 months before study enrollment. Results were stratified by nocturia frequency (1, 2-3, >= 4 episodes/night).
RESULT(S): 899 patients were enrolled. With increasing nocturia episodes, EQ-5D mean scores decreased (0.86 +/- 0.1, 0.83 +/- 0.2, 0.80 +/- 0.2 for 1, 2 to 3, >= 4 episodes respectively; P < 0.01), while impact on work productivity increased in working participants (n = 196; 9.6% +/- 17.7%, 18.4% +/- 23.0%, 22.3% +/- 28.0% for 1, 2-3, >= 4 episodes; P = 0.01). The proportion of patients visiting a primary care physician (85.1%, 93.0%, 91.0% for 1, 2-3, >= 4 episodes; P = 0.005), as well as the number of visits/patient (2.6 +/- 1.9, 3.3 +/- 2.6, 3.5 +/- 2.3 for 1, 2-3, >= 4 episodes; P = 0.002), increased with nocturia frequency. The proportion of patients with any prescription claim (76.8%, 90.3%, 88.3% for 1, 2-3, >= 4 episodes; P < 0.001) and the mean number of prescriptions/patient (16.8 +/- 13.4, 20.9 +/- 16.0, 25.1 +/- 20.6 for 1, 2-3, >= 4 episodes; P < 0.001) increased with nocturia frequency. ER visits and hospitalizations followed similar trends but were not statistically significant due to the small number of patients with qualifying event(s). Health plan paid total costs, including hospitalizations, ER visits, outpatient visits, and prescriptions, also increased with nocturia frequency (median costs: $1,618, $2,424, $2,969 for 1, 2-3, >= 4 episodes).
CONCLUSION(S): The humanistic and economic burden of nocturia increases with nocturic frequency. This suggests that management focused on reducing nocturic episodes may reduce HRU and associated costs and improve quality of life among patients with nocturia

OBJECTIVE: to review key guidelines on the management of urinary incontinence in order to guide clinical management in a practical way. MATERIALS AND METHODS: guidelines produced by the European Association of Urology (updated in 2014), the Canadian Urological Association (updated in 2012), the International Consultation on Incontinence (updated in 2012), and the National Collaborating Centre for Women's and Children's Health (updated in 2013) were examined and their recommendations compared. In addition, specialized guidelines produced by the collaboration between the American Urological Association and the Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction on overactive bladder and the use of urodynamics were reviewed. The Appraisal of Guidelines for Research & Evaluation II (AGREE) Instrument was used to evaluate the quality of these guidelines. RESULTS: there is general agreement between the groups on the recommended initial workup and the use of conservative therapies for first line treatment, with limited role for imaging or invasive testing in the uncomplicated patient. These groups have greater variability in their recommendations for invasive procedures, however generally the mid-urethral sling is recommended for uncomplicated stress urinary incontinence, with different recommendations on the approach as well as the comparability to other treatments, such as the autologous fascial sling. CONCLUSION: this Guideline of Guidelines provides a summary of the salient similarities and differences between prominent groups on the management of urinary incontinence

Stress urinary incontinence (SUI) is said to effect up to 80 % of all women who complain of some type of urinary leakage. As education about the diagnosis and treatment of SUI becomes more widespread, there is a need for understanding the efficacy and potential complications of the therapies used to treat this condition. It is widely accepted that the gold standard for treatment of SUI is mid-urethral sling (MUS). One significant complication of the MUS procedure is subsequent bladder outlet obstruction (BOO). We review the incidence and etiology of BOO following MUS and hope this document can be used as a guide for identifying patients who may be affected by postsurgical BOO. Additionally, we discuss modalities for achieving a timely and accurate diagnosis and highlight recent evidence regarding the various applications of urodynamic studies, when concerned for BOO. Lastly, various managements of this complication are discussed. This chapter serves as a comprehensive overview of BOO after incontinence procedures, highlighting the recent research contributions, which have enhanced our understanding of this potential complication when treating SUI

CASE: Xanthogranulomatous inflammation of the prostate is a rare condition that can cause lower urinary tract symptoms and may be mistaken for adenocarcinoma. It is often seen on prostate biopsy, but can usually be treated conservatively with temporary catheterization, alpha blockade, and allowing time for improvement. We present a case of a 78-year-old man found to have a 318 g prostate secondary to xanthogranulomatous inflammation. OUTCOME: After a negative MRI-guided biopsy to rule out malignancy, the patient was treated successfully with open suprapubic prostatectomy with significant improvement in voiding symptoms. CONCLUSION: This case highlights the ability of this clinical and pathologic entity to cause significant prostatic enlargement, how it is diagnosed, and the possible role of surgical therapy in its treatment.

Multiple sclerosis (MS) can be a debilitating neurological condition that attributes significant morbidity to bladder dysfunction. Although many effective treatment options exist, symptomatic patients are often underdiagnosed and undertreated. The purpose of this article is to give an overview of the current literature including new screening tools to identify symptomatic patients and updates on treatment options including medications, botulinum toxin, and neuromodulation.