The physiology and pharmacology of the lower urinary tract

The lower urinary tract comprises the urinary bladder, the urethra and prostate in men, and is concerned with the storage of urine and its voluntary expulsion from the body when socially convenient. These mutually exclusive states are mediated by complex neural networks that when dysfunctional generate bothersome and highly prevalent lower urinary tract symptoms (LUTS). Lower urinary tract symptoms are often idiopathic and not pathology specific and most result from bladder outflow obstruction, disorders of bladder contractility or conditions which increase bladder sensitivity and a combination of any of these states. Despite the precise mechanisms of symptom generation being unclear, the receptor mechanisms involved in controlling lower urinary tract function can be pharmacologically manipulated to achieve useful clinical outcomes.     

Patient‐reported outcomes from SYNERGY,a randomized,double‐blind,multicenter study evaluating combinations of mirabegron and solifenacin compared with monotherapy and placebo in OAB patients

Aims

To evaluate patient‐reported outcomes (PROs) of combinations of solifenacin and mirabegron compared with solifenacin and mirabegron monotherapy and with placebo in patients with overactive bladder (OAB) from the SYNERGY trial.

Methods

Following a 4‐week placebo run‐in, period patients (≥18 years) with OAB were randomized 2:2:1:1:1:1 to receive solifenacin 5 mg + mirabegron 25 mg (combination 5 + 25 mg), solifenacin 5 mg + mirabegron 50 mg, (combination 5 + 50 mg), solifenacin 5 mg, mirabegron 25 mg, mirabegron 50 mg or placebo for 12 weeks, followed by a 2‐week washout period. At each visit, PROs related to quality of life, symptom bother, and treatment satisfaction were assessed, including OAB‐q Symptom Bother score, health‐related quality of life (HRQOL) Total score, treatment satisfaction‐visual analogue scale (TS‐VAS), and patient perception of bladder condition (PPBC) questionnaires.

Results

Overall, 3527 patients were randomized into the study, with 3494 receiving double‐blind treatment. At end of treatment (EoT), both combination groups showed greater improvements in OAB‐q Symptom Bother score compared with the monotherapy groups (nominal P < 0.001). Statistically significant improvements in HRQOL Total scores were observed in the combination groups versus monotherapy groups (P ≤ 0.002). For both combination groups, the OAB‐q Symptom Bother score responder rates at EoT were statistically significantly higher versus mirabegron monotherapy (P < 0.05). The mean adjusted changes from baseline to EoT for PPBC were greater in the combination groups compared with monotherapy groups.

Conclusions

PROs showed that combination therapy provided clear improvements and an additive effect for many HRQOL parameters, including OAB‐q Symptom Bother score, HRQOL Total score, and PPBC.     

A review of detrusor overactivity and the overactive bladder after radical prostate cancer treatment

There are various forms of treatment for prostate cancer. In addition to oncologic outcomes, physicians, and increasingly patients, are focusing on functional and adverse outcomes. Symptoms of overactive bladder (OAB), including urinary frequency, urgency and incontinence, can occur regardless of treatment modality. This article examines the prevalence, pathophysiology and options for treating OAB after radical prostate cancer treatment. OAB seems to be more common and severe after radiation therapy than after surgical therapy and even persisted longer with complications, suggesting an advantage for surgery over radiotherapy. Because OAB that occurs after radical prostate surgery or radiotherapy can be difficult to treat, it is important that patients are made aware of the potential development of OAB during counselling before decisions regarding treatment choice are made. To ensure a successful outcome of both treatments, it is imperative that clinicians and non‐specialists enquire about and document pretreatment urinary symptoms and carefully evaluate post‐treatment symptoms.     

Improvements in overactive bladder syndrome after polypropylene mesh surgery for cystocele

Background: The International Continence Society has defined overactive bladder syndrome (OABS) by the following set of symptoms: 'urgency, with or without urge incontinence, usually with urinary frequency and nocturia'. OABS and cystocele often coexist.
Aim: This study aimed to analyse the changes in the overactive bladder symptom score (OABSS) of women followed up for one year after anterior repair surgery performed using a polypropylene mesh. In this surgery, a tape with four straps designed for optimum tissue holding capacity was fixed to the obturator foramen.
Material and methods: Thirty-four women were operated using the abovementioned mesh. The OABSS, maximal urinary flow rate (Qmax) and postvoid residual (PVR) volume were evaluated pre- and post-surgery.
Results: We observed significant improvements in the OABSS and quality of life scores before and after one year of surgery. The surgery was significantly effective in improving urgency, daytime frequency, incontinence, the Qmax and the PVR volume. No significant change in nocturia was observed post-surgery.
Conclusions: Our study confirmed the efficacy of the propylene mesh introduction surgery for cystocele for the improvement of OABS symptoms.     

Comparison of Outcome Assessments in Patients with Overactive Bladder Receiving Anticholinergics

Objectives: Patient‐reported outcomes (PRO) reflect treatment benefits from the patient's perspective, and are a subjective method of evaluating the efficacy of overactive bladder (OAB) treatment. We examined the changes in voiding diaries and health‐related quality of life (HRQL) according to patient‐perceived treatment benefits in patients with OAB receiving propiverine. Methods: Thirty‐two patients (mean age ± S.D: 55.1 ± 14.1 years) with OAB were treated with 20 mg propiverine once daily for 12 weeks. The 3‐day voiding diary and the Korean version of the Overactive Bladder Questionnaire (OABq), which includes an eight‐item bothersome symptom scale, as well as 25 HRQL items, were assessed at baseline and at 12 weeks. Finally, patient perception of treatment benefit was evaluated as “no benefit,”“little benefit,” or “much benefit” after treatment. Results: According to patients' perceptions of treatment benefits, 16 (50%) patients perceived “much benefit” from their treatment (group A) and 16 (50%) patients perceived “little benefit” or “no benefit” from their treatment (group B). In both groups, there were significant improvements in the micturation parameters, OABq bothersome symptoms, and total HRQL score after 12 weeks of treatment (P < 0.05). Although there were no significant differences in the voiding diary parameters between the two groups, patients in group A showed significant improvement of the OABq bothersome symptom and total HRQL score compared to group B (P < 0.05). Conclusion: Anticholinergic treatment improves both OAB symptoms and HRQL, and patients' perceptions of treatment benefits correlate better with the OABq than with the voiding diary parameters.     

Overactive Bladder in Female Patients with Chronic Diseases Visiting Primary Care Doctors: Effect of Age on Prevalence and Bothersomeness

Objectives: We evaluated the effects of age on the prevalence and bothersomeness of overactive bladder (OAB) in female patients with chronic diseases visiting primary care doctors. Methods: We used the pooled data of the SURPRISE survey in which 121 doctors and 1388 female patients aged 40 years or older responded to questionnaires. Results: The OAB prevalence rate in patients was estimated by doctors to be 9.5%. However, the OAB prevalence rate according to patients, as defined by the OAB symptom score, was 22.3%. The rate was increased with age. The number of patients with OAB was much higher than estimated by doctors. Approximately 25% of patients were dissatisfied with their present urinary condition. The rate was increased with age. Dissatisfaction with present urinary condition was strongly correlated with severe urgency score in all age groups. In elderly patients, contribution of urgency incontinence and nocturia to dissatisfaction was also increased. Thirteen percent of patients were receiving treatment for their OAB. However, 15.8% were untreated, regardless of having OAB, suggesting that treated patients comprise less than half of all OAB patients. This tendency was observed in all age groups. In the correlation between satisfaction with pharmacological treatment and each OAB symptom, contribution of urgency to satisfaction with pharmacological treatment was the highest. Conclusion: Urgency is the most bothersome symptom and shows the highest contribution to treatment satisfaction. In elderly patients, urgency incontinence and nocturia are proportionally greater problems. Management of urgency is essential for improving quality of life and satisfaction with treatment in OAB patients.     

Transcutaneous Tibial Nerve Stimulation in the Management of Overactive Bladder: A Scoping Review

ObjectiveOveractive bladder (OAB) is a condition that has physical, social, psychosocial, and financial impacts. Transcutaneous tibial nerve stimulation (TTNS) is a modality that stimulates the nerve root fibers of L5-S3, the same spinal segments of the parasympathetic nervous system as the bladder. This scoping review aims to identify current literature available on the feasibility and outcomes of TTNS as a first-line treatment option for OAB.Materials and MethodsA scoping review of six electronic data bases was performed to identify full-text articles from 2015 that explored the impact of TTNS on OAB and bladder dysfunction in people aged >18 years.ResultsA total of 15 articles met the inclusion criteria. TTNS was compared with sham treatment, parasacral stimulation, pelvic floor muscle training (PFMT), anticholinergic medication, and percutaneous tibial nerve stimulation (PTNS). Heterogeneity in treatment application and parameters existed, with variations in treatment duration, frequency of use, and treatment settings such as pulse width (μs) and frequency (Hz). Results indicated that TTNS has efficacy equal to PFMT and PTNS in the management of OAB; however, it is not as efficacious as anticholinergic medication.ConclusionsTTNS is a promising first-line management option for people with OAB, particularly in the older population and for those with neurogenic bladder. It can provide symptomatic relief from urinary incontinence, frequency, urgency, and nocturia, while avoiding the bothersome side effects of more invasive or pharmaceutical therapies. Heterogeneity in treatment parameters limits generalizability and translation of the most appropriate clinical application and should be considered in future trials.