Aims
The purpose of this review is to update the current understanding of dimethyl sulfoxide (DMSO) and its role in the treatment of interstitial cystitis (IC).
Methods
A systematic review was ...conducted using the PRIMSA checklist to identify published articles involving intravesical DMSO for the treatment of IC.
Results
Thirteen cohort studies and three randomized‐controlled trials were identified. Response rates relying on subjective measurement scores range from 61 to 95%. No increased efficacy was found with “cocktail” DMSO therapy. Great variation existed in diagnostic criteria, DMSO instillation protocols and response measurements.
Conclusions
The current evidence backing DMSO is a constellation of cohort studies and a single randomized‐controlled trial versus placebo. The optimal dose, dwell time, type of IC most likely to respond to DMSO, definitions of success/failure and the number of treatments are not universally agreed upon. Improvements in study design, phenotyping patients based on symptoms, as well as the emergence of reliable biomarkers of the disease may better guide the use of DMSO in the future.
Study Type – Symptom prevalence (prospective cohort) Level of Evidence 1b
OBJECTIVE
To evaluate patient‐reported reasons for discontinuing antimuscarinic prescription medications for overactive ...bladder (OAB).
PATIENTS AND METHODS
A phase 1 screening survey was sent to a representative sample of 260 000 households in the USA to identify patients using antimuscarinic agents for OAB. A detailed phase‐2 follow‐up survey was sent to 6577 respondents with one or more antimuscarinic prescriptions for OAB in the 12 months before the phase 1 survey. The follow‐up survey included questions about demographics, clinical characteristics, antimuscarinic use, beliefs about OAB, treatment expectations, OAB symptom bother, and pre‐coded reasons for discontinuation. Patients who reported discontinuing one or more OAB medication during the 12 months before phase 2 were grouped by reason, using latent class analysis (LCA); the Lo‐Mendell‐Rubin likelihood statistical test was used to determine the number of classes. Conditional probabilities of reasons for discontinuation were calculated for each class. Multivariable logistic regression was used to assess the influence of demographic and clinical characteristics on class assignment.
RESULTS
In all, 162 906 (63%) and 5392 (82%) useable responses were returned in phases 1 and 2, respectively; the demographics were similar in respondents and nonrespondents in both phases. In all, 1322 phase 2 respondents (24.5%) reported discontinuing one or more antimuscarinic drugs during the 12 months before phase 2. LCA identified two classes (Lo‐Mendell‐Rubin statistic, P = 0.01) based on reasons for discontinuation. Most respondents (89%) reported discontinuing OAB medication primarily due to unmet treatment expectations and/or tolerability; many respondents in this class switched to a new antimuscarinic agent. A smaller group (11%) indicated a general aversion to taking medication. Age, sex, race, income, and history of incontinence were not predictive of class assignment.
CONCLUSIONS
Expectations about treatment efficacy and side‐effects are the most important considerations in discontinuing OAB medications for most patients. Interventions to promote realistic expectations about treatment efficacy and side‐effects might enhance adherence.
Men with overactive bladder and other lower urinary tract symptoms may not respond to monotherapy with antimuscarinic agents or alpha-receptor antagonists.
To evaluate the efficacy and safety of ...tolterodine extended release (ER), tamsulosin, or both in men who met research criteria for both overactive bladder and benign prostatic hyperplasia.
Randomized, double-blind, placebo-controlled trial conducted at 95 urology clinics in the United States involving men 40 years or older who had a total International Prostate Symptom Score of 12 or higher and, an International Prostate Symptom Score quality-of-life (QOL) item score of 3 or higher, a self-rated bladder condition of at least moderate bother, and a bladder diary documenting micturition frequency (>or=8 micturitions per 24 hours) and urgency (>or=3 episodes per 24 hours), with or without urgency urinary incontinence. Patients were recruited between November 2004 and February 2006, and the study was completed May 2006.
Patients were randomly assigned to receive placebo (n = 222), 4 mg of tolterodine ER (n = 217), 0.4 mg of tamsulosin (n = 215), or both tolterodine ER plus tamsulosin (n = 225) for 12 weeks.
Patient perception of treatment benefit, bladder diary variables, International Prostate Symptom Scores, and safety and tolerability were assessed.
A total of 172 men (80%) receiving tolterodine ER plus tamsulosin reported treatment benefit by week 12 compared with 132 patients (62%) receiving placebo (P<.001), 146 (71%) receiving tamsulosin (P=.06 vs placebo), or 135 (65%) receiving tolterodine ER (P=.48 vs placebo). Patients receiving tolterodine ER plus tamsulosin compared with placebo experienced significant reductions in urgency urinary incontinence (-0.88 vs -0.31, P=.005), urgency episodes without incontinence (-3.33 vs -2.54, P=.03), micturitions per 24 hours (-2.54 vs -1.41, P<.001), and micturitions per night (-0.59 vs -0.39, P.02). Patients receiving tolterodine ER plus tamsulosin demonstrated significant improvements on the total International Prostate Symptom Score (-8.02 vs placebo, -6.19, P=.003) and QOL item (-1.61 vs -1.17, P=.003). All interventions were well tolerated. The incidence of acute urinary retention requiring catheterization was low (tolterodine ER plus tamsulosin, 0.4%; tolterodine ER, 0.5%; tamsulosin, 0%; and placebo, 0%).
These results suggest that treatment with tolterodine ER plus tamsulosin for 12 weeks provides benefit for men with moderate to severe lower urinary tract symptoms including overactive bladder. Clinical Trials Registration clinicaltrials.gov Identifier: NCT00147654.
Purpose The Overactive Bladder Innovative Therapy trial was a randomized, multicenter, controlled study that compared the effectiveness of percutaneous tibial nerve stimulation to extended-release ...tolterodine. The reduction in overactive bladder symptoms along with global response assessments was evaluated. Materials and Methods A total of 100 adults with urinary frequency were randomized 1:1 to 12 weeks of treatment with weekly percutaneous tibial nerve stimulation or to 4 mg daily extended-release tolterodine. Voiding diaries and an overactive bladder questionnaire were completed at baseline and at the end of therapy to compare 24-hour voiding frequency, urinary urge incontinence episodes, voids causing waking, volume voided, urgency episodes and quality of life indices. Global response assessments were completed by subjects and investigators after 12 weeks of therapy. Results The global response assessment demonstrated that subject assessment of overactive bladder symptoms compared to baseline was statistically significant in the percutaneous tibial nerve stimulation arm with 79.5% reporting cure or improvement compared to 54.8% of subjects on tolterodine (p = 0.01). Assessments by investigators were similar but did not reach statistical significance (p = 0.05). After 12 weeks of therapy objective measures improved similarly in both groups for reductions in urinary frequency, urge urinary incontinence episodes, urge severity and nighttime voids, as well as for improvement in voided volume. There were no serious adverse events or device malfunctions. Conclusions This multicenter, randomized trial demonstrates that percutaneous tibial nerve stimulation is safe with statistically significant improvements in patient assessment of overactive bladder symptoms, and with objective effectiveness comparable to that of pharmacotherapy. Percutaneous tibial nerve stimulation may be considered a clinically significant alternative therapy for overactive bladder.
The large-conductance voltage- and Ca(2+)-activated K(+) (BK) channel is expressed in many smooth muscle types, but its role in human detrusor smooth muscle (DSM) is unclear. With a multidisciplinary ...approach spanning channel molecules, single-channel activity, freshly isolated human DSM cells, intact DSM preparations, and the BK channel specific inhibitor iberiotoxin, we elucidated human DSM BK channel function and regulation. Native human DSM tissues were obtained during open surgeries from patients with no preoperative history of overactive bladder. RT-PCR experiments on single human DSM cells showed mRNA expression of BK channel α-, β(1)-, and β(4)-subunits. Western blot and immunocytochemistry confirmed BK channel α, β(1), and β(4) protein expression. Native human BK channel properties were described using the perforated whole cell configuration of the patch-clamp technique. In freshly isolated human DSM cells, BK channel blockade with iberiotoxin inhibited a significant portion of the total voltage step-induced whole cell K(+) current. From single BK channel recordings, human BK channel conductance was calculated to be 136 pS. Voltage-dependent iberiotoxin- and ryanodine-sensitive transient BK currents were identified in human DSM cells. In current-clamp mode, iberiotoxin inhibited the hyperpolarizing membrane potential transients and depolarized the cell resting membrane potential. Isometric DSM tension recordings revealed that BK channels principally control the contractions of isolated human DSM strips. Collectively, our results indicate that BK channels are fundamental regulators of DSM excitability and contractility and may represent new targets for pharmacological or genetic control of urinary bladder function in humans.
To present the clinical and radiological characteristics of women with severe structural deterioration of the bladder and upper urinary tract secondary to Primary Bladder Neck Obstruction (PBNO), and ...their outcomes after bladder neck incision (BNI).
Retrospective evaluation of adult women who underwent BNI for PBNO at one institution. Patients were assessed for symptoms, renal function, structural abnormalities of the urinary tract and video-urodynamics. PBNO diagnosis was confirmed with video-urodynamics in all patients. BNI was performed at the 4-5 and/or 7-8 o'clock positions. Postoperative symptoms, PVR, uroflowmetry and renal function were evaluated and compared to baseline.
Median patient age was 56.5 years (range 40-80). All presented with urinary retention-four were on clean intermittent Catheterization (CIC) and two with a Foley catheter. All patients had bladder wall thickening and diverticula. Four women had elevated creatinine levels, bilateral hydronephrosis was present in five (83.3%). After BNI, all patients resumed spontaneous voiding without the need for CIC. Median Qmax significantly improved from 2.0 1.0-4.0 mL/s to 15 10-22.7 mL/s (p = 0.031). Median PVR decreased from 150 to 46 22-76 mL (p = 0.031). There were no postoperative complications. Creatinine levels returned to normal in 3/4 (75%) patients.
PBNO in women may result in severe damage to the bladder and upper urinary tract. Despite severe structural abnormalities of the bladder, BNI was effective in reducing symptoms and improving structural and functional abnormalities of the lower and upper urinary tract.
Purpose The authors of this guideline reviewed the literature regarding use of urodynamic testing in common lower urinary tract symptoms. The findings are intended to assist clinicians in the ...appropriate selection of urodynamic tests, following an evaluation and symptom characterization. Materials and Methods A systematic review of the literature using the MEDLINE® and EMBASE databases (searched from 1/1/90 to 3/10/11) was conducted to identify peer-reviewed publications relevant to using urodynamic tests for diagnosis, determining prognosis, guiding clinical management decisions and improving patient outcomes in patients with various urologic conditions. The review yielded an evidence base of 393 studies after application of inclusion/exclusion criteria. These publications were used to create the evidence basis for characterizing the statements presented in the guideline as Standards, Recommendations or Options. When sufficient evidence existed, the body of evidence for a particular treatment was assigned a strength rating of A (high), B (moderate) or C (low). In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinion. Results The evidence-based guideline statements are provided for diagnosis and overall management of common LUTS conditions. Conclusions The Panel recognizes that each patient presenting with LUTS is unique. This Guideline is intended to serve as a tool facilitating the most effective utilization of urodynamic testing as part of a comprehensive evaluation of patients presenting with LUTS.
The purpose of this review is to summarize and evaluate the most recent literature on the epidemiology, etiology, and treatment of lower urinary tract symptoms (LUTS) in women.
Several authors have ...studied characteristics of populations of women with LUTS and addressed care-seeking behavior for these conditions. Multiple investigators also sought greater understanding of the urinary microbiome and its relationship to LUTS in women. Evidence for the treatment of overactive bladder and stress urinary incontinence is being synthesized and innovative treatments are being rigorously studied.
Investigations and high quality research continue to shed light on the epidemiology, diagnosis, and management of LUTS in women.
Purpose We updated the 1997 American Urological Association guideline on female stress incontinence. Materials and Methods MEDLINE® searches of English language publications from 1994 and new ...searches of the literature published between December 2002 and June 2005 were performed using identified MeSH terms. Articles were selected for the index patient defined as the otherwise healthy woman who elected to undergo surgery to correct stress urinary incontinence or the otherwise healthy woman with incontinence and prolapse who elected to undergo treatment for both conditions. Results A total of 436 articles were identified as suitable for inclusion in the meta-analysis, and an additional 155 articles were suitable for complications data only due to insufficient followup of efficacy outcomes in the latter reports. Surgical efficacy was defined using outcomes pre-specified in the primary evidence articles. Urgency (resolution and de novo) was included as an efficacy outcome due to its significant impact on quality of life. The primary efficacy outcome was resolution of stress incontinence measured as completely dry (cured/dry) or improved (cured/improved). Complications were analyzed similarly to the efficacy outcomes. Subjective complications (pain, sexual dysfunction and voiding dysfunction) were also included as a separate category. Conclusions The surgical management of stress urinary incontinence with or without combined prolapse treatment continues to evolve. New technologies have emerged which have impacted surgical treatment algorithms. Cystoscopy has been added as a standard component of the procedure during surgical implantation of slings.
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