Urinary brain-derived neurotrophic factor: a potential biomarker for objective diagnosis of overactive bladder

Purpose

To investigate the diagnostic performance of urinary brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) as potential biomarkers for overactive bladder (OAB).

Methods

Ninety women diagnosed with OAB and 45 normal controls without OAB were enrolled. Urine samples were collected from all subjects. Urinary BDNF and NGF levels were measured using enzyme-linked immunosorbent assays. Results normalized by urinary creatinine (Cr) levels were compared between OAB groups and controls. Symptom severity was assessed using overactive bladder symptom score.

Results

Urinary BDNF and NGF levels were elevated in OAB groups but not in controls. Mean (SD) baseline BDNF and NGF levels normalized by Cr levels were significantly higher in OAB subjects than in controls (20.609 ± 23.932 vs. 1.779 ± 0.729, p < 0.01) and (0.258 ± 0.264 vs. 0.081 ± 0.028, p < 0.01), respectively. Urinary BDNF/Cr levels were 80-fold higher than NGF/Cr levels in OAB subjects. Receiver operating characteristic curves for assessing urinary BDNF/Cr levels in OAB groups showed sensitivity and specificity of 93.33 and 88.89 %, respectively. Urinary BDNF levels were associated with OAB symptom severity.

Conclusions

Urinary BDNF/Cr levels are elevated in women with OAB and are significantly associated with symptom severity. No elevation of BDNF is found in women without OAB. BDNF analysis has better sensitivity than NGF in detecting OAB in subjects without other lower urinary tract disorders. Results of the present study suggest a potential role for BDNF as an objective biomarker for OAB diagnosis.     

Association of inflammaging (inflammation + aging) with higher prevalence of OAB in elderly population

Introduction

Although epidemiology studies consistently report increased prevalence of overactive bladder (OAB) with age, an accurate deciphering of causative links between the two entities remains elusive. Studies on aged rodent bladder have so far yielded contradictory results on age-associated changes in muscarinic receptors, which highlight the challenge posed by species differences in understanding OAB pathology. We hypothesized that age-related biochemical changes in bladder leading to altered bladder function will be reflected in altered urinary proteome of elderly OAB patients.

Methods

Single time point urine specimens were obtained from 140 OAB patients in the age range of 25–90 years of either sex coming routinely to the urology clinics. Eight chemokines in urine were measured by MILLIPLEX MAP human cytokine/chemokine multiplex immunoassay and ELISA. Multivariate and univariate statistical analyses were done to determine association of age with urinary chemokines in OAB patients.

Results

In agreement with age-dependent higher prevalence of OAB, the logistic regression of the data also revealed the significant association of OAB symptoms with age [odds ratio (OR) 1.12; 95 % CI, (1.072, 1.187), p = 0.0001]. Univariate analysis of 8 urinary proteins revealed an age-associated elevation of NGF (nerve growth factor) in 137 out of 140 OAB patients [Pearson r = 0.274; 95 %CI (0.112–0.422); p = 0.001]. Modest correlation with age was also noted for MCP-1 (monocyte chemoattractant protein-1), which was detected in 115 OAB patients, and the remaining chemokines were undetectable in nearly two-third of OAB patients included in our cohort.

Conclusions

Based on our findings, we postulate that age-associated biochemical changes may accentuate the inflammation associated with OAB. Urinary NGF elevation in elderly OAB patients may be a homeostatic response to counter the senescence of bladder nerves and arrest the progression of OAB into detrusor hyperactivity with impaired contractility. Likewise, elevation of MCP-1 may be related to decreased muscle mass and increased content of adipose tissue in bladder of elderly OAB patients. Urinary NGF and MCP-1 can serve as surrogate markers for monitoring age-associated biochemical changes and the effect of therapeutic interventions in OAB patients.     

Wertigkeit des ?nerve growth factor“ beim Syndrom der überaktiven Blase

Objectives

Several studies discussing the pathology of overactive bladder suggested changes in urinary proteins. The neurotrophin “nerve growth factor” (NGF) seems to be an important marker in overactive bladder syndrome (OAB). In this prospectively designed study we evaluated NGF blood levels (sNGF) initially and after injection of botulinum toxin type A (BTX-A) in the detrusor muscle in patients suffering from idiopathic OAB.

Materials and methods

Blood samples were obtained from 26 patients (66.5 years, 28–83) with idiopathic OAB. sNGF levels were measured before and 4 weeks after BTX-A treatment by enzyme-linked immunosorbent assay (ELISA). A group of 32 healthy persons with normal bladder function served as controls (41 years, 19–60). sNGF was evaluated in relation to clinical data and the severity of OAB (wet/dry).

Results

Significantly higher sNGF levels were detected in patients with OAB compared to the control group (58.8 vs 2.0 pg/ml, p<0.005). Further, sNGF levels were elevated in patients with wet OAB compared to patients with dry OAB (85.0 vs 0.73 pg/ml, p<0.005). Patients > 60 years showed significantly higher sNGF levels (77.2 vs 8.9 pg/ml, p<0.05) compared to younger OAB patients. After BTX-A therapy sNGF levels decreased significantly compared to baseline (p<0.005).

Conclusion

NGF appears to play a decisive role in OAB. Its use as a biomarker in both the diagnostics and follow-up after therapy seems promising. To what extent sNGF can be useful as a biomarker or in therapy monitoring needs to be examined prospectively in a larger population.     

Changes in urinary nerve growth factor and prostaglandin E2 in women with overactive bladder after anticholinergics

Introduction and hypothesis

The aim of this study is to investigate changes in urinary nerve growth factor (NGF) and prostaglandin E₂ (PGE₂) in women with overactive bladder (OAB) following anticholinergic treatment.

Methods

A total of 30 female patients with OAB were enrolled and the control group included 15 healthy women who did not present any bladder symptoms. All subjects with OAB recorded voiding diaries, underwent urodynamic study, and were evaluated for urgency grade. They received anticholinergic treatment for 4 weeks, after which they were again evaluated for urinary urgency grade and voiding diaries. OAB patients were classified into three groups according to the change on the 5-point Urinary Sensation Scale after the treatment: group 1 (no change in urgency grade), group 2 (1 point of improvement), and, group 3 (more than 2 points of improvement). Urinary NGF and PGE₂ levels between controls and OAB patients (before and after treatment in groups 1, 2, and 3) were compared.

Results

Urinary NGF and PGE₂ levels were significantly higher in OAB patients than in the controls. NGF levels were not significantly different between pre- and post-treatment in groups 1 and 2. However, in group 3, NGF levels were significantly decreased after treatment. PGE₂ levels were not significantly different between pre- and post-treatment in either group.

Conclusions

NGF and PGE₂ have important roles in the development of OAB symptoms in women. Initial reduction of urgency severity after anticholinergic treatment in women with OAB could be associated with decreasing urinary NGF levels.     

Urinary nerve growth factor correlates with the severity of urgency and pain

Introduction and hypothesis

Urinary nerve-growth-factor (NGF) level reflected the severity of urgency in patients with lower urinary tract symptoms (LUTS) and pain in patients with Bladder pain syndrome/interstitial cystitis (BPS/IC). The aim of this study was to investigate the levels of biomarkers, nerve growth factor (NGF), and prostaglandin E2 (PGE₂) among disease groups sharing similar urinary symptoms and to elucidate which symptoms are related to individual biomarker levels.

Methods

We studied 83 patients with LUTS who visited our outpatient clinic from May 2011 to December 2012. On the basis of clinical symptoms and a 3-day voiding diary, patients were classified into three groups: those with frequency (n?=?13), overactive bladder (OAB) (n?=?35), and BPS/IC (n?=?35). Patients with stress urinary incontinence (SUI) or microscopic hematuria served as controls (n?=?24). Storage symptoms were evaluated based on OAB symptom score (OAB-SS).

Results

Mean patient age was 62.08?±?11.47 (range, 23–84). Urinary NGF and creatinine-normalized NGF levels were significantly increased in those with OAB (201.90 and 4.08, respectively) and BPS/IC (173.71 and 2.72) compared with controls (77.77 and 1.29) and those with frequency (67.76 and 1.23). Neither value significantly differed between OAB and BPS/IC patients or between controls and frequency patients. Urinary PGE₂ and creatinine-normalized PGE₂ levels were not significantly different among groups. On linear regression analysis, urinary NGF levels were significantly correlated with urgency severity overall (R?=?0.222) and also pain in BPS/IC patients (R?=?0.409).

Conclusions

The levels of urinary NGF were elevated in patients with OAB and BPS/IC but not those with frequency and reflected the severity of urgency. In BPS/IC patients, urinary NGF increased with pain severity.     

Pelvic organ prolapse quantification in women referred with overactive bladder

Introduction and hypothesis

A study was carried out to investigate the relationship of anterior vaginal wall descent or prolapse to overactive bladder and its potential mechanisms, advancing the management of overactive bladder (OAB).

Methods

Two hundred twenty-six consecutive women with OAB symptoms were prospectively studied using OAB questionnaire (OAB-q) and pelvic organ prolapse quantification (POP-Q). According to POP-Q staging, they were divided into three groups: stages 0, I, and II. For statistical analysis, a one-way ANOVA was used to test for significant differences with Student–Newman–Keuls post hoc analysis for continuous variables (OAB-q symptom severity, health-related quality of life total scores, and age) and chi-squared test for discrete variable (number of menopausal women).

Results

Twenty-two women (9.73%) did not show any prolapse on examination; 204 (90.26%) had anterior vaginal wall descent or prolapse. The outcome statistics denoted that the difference in OAB-q scores among three groups has statistical significance (P?<?0.05). Anterior vaginal wall descent or prolapse may have associations with OAB.

Conclusions

Anterior vaginal wall descent or prolapse may have associations with OAB and is directly correlated to OAB severity.     

Associations between subjective overactive bladder symptoms and objective parameters on bladder diary and filling cystometry

Introduction and hypothesis

A study was conducted to assess associations between different overactive bladder (OAB) symptoms and their outcomes on bladder diary and filling cystometry parameters.

Methods

We performed a retrospective cohort study in database of 6,876 Urinary Distress Inventories, 3,185 bladder diaries and 2,153 filling cystometries from women referred to our urogynecological center between 2003 and 2009. Women were dichotomized into two groups. Group I: those women without symptoms, and those with symptoms that were not bothersome. Group II: women with bothersome symptoms. Data obtained from bladder diaries were: daytime urinary frequency, nocturnal frequency, minimum voided volume, maximum voided volume, average voided volume, and incontinence episodes. From filling cystometries, volumes at first desire to void, normal desire to void, strong desire to void and maximum cystometric capacity, were extracted. Univariate and multiple linear regression analysis were performed to determine associations between OAB symptoms and bladder diary and filling cystometry measurements.

Results

After multivariate analysis the objective daytime frequency was most strongly associated with the frequency symptom (β 0.27, p?<?0.05), night time frequency with the nocturia symptom (β 0.40, p?<?0.05) and the number of incontinence episodes with the urge incontinence symptom (β 0.37, p?<?0.05). Both frequency and nocturia symptoms were significantly associated with bladder diary and cystometry filling volumes, and their effect size was the same. The urgency symptom proved to be poorly associated with objective parameters.

Conclusions

In contrast to the frequency and nocturia symptom, the urgency symptom is poorly associated with objective parameters on bladder diary and filling cystometry. Therefore, the current practice of using frequency and incontinence episodes in outcome research of OAB trials is justified.     

Alterations of heart rate variability in women with overactive bladder syndrome

Introduction and hypothesis

Our objective was to compare autonomic nervous system function between women with an overactive bladder (OAB) and control participants during regulated bladder filling.

Methods

Twenty-four women, nine with OAB and 15 without (control), were instructed to drink 1.5 l of water at a rate of 250?ml every 5?min during continuous electrocardiogram (ECG) monitoring. Participants were asked to indicate first sensations of filling (FSF), first desire to void (FDV), strong desire to void (SDV), and maximal bladder capacity (MC). ECG signals were used to assess heart rate variability, which were analyzed in time and frequency domains using the fast Fourier transform. The low-frequency (LF)and high-frequency (HF) spectral bands were used to asses sympathetic and parasympathetic pathways, respectively.

Results

During the bladder-filling phase, women with OAB had significantly lower LF values (at the MC phase 5.4?±?1.4?ms²/Hz vs. 6.4±?0.6?ms²/Hz in the control group, p?=?0.02). In the control group, LF increased continuously, whereas in the OAB group, LF increased until the sensation of SDV and then abruptly decreased to baseline values. MC was lower in women with OAB (372?±?153?ml vs. 592?±?298?ml, p?Conclusions Reduced sympathetic tone in women with OAB may explain their attainment of lower volumes of MC and their sensation of urgency. The rapid decrease in sympathetic neural activity that accompanies the sensation of an SDV may be related to the pathophysiology of the urgency symptom in these women.     

Clinical and urodynamic differences among women with overactive bladder according to the presence of detrusor overactivity

Introduction and hypothesis

We tried to determine whether clinical and urodynamic differences exist between women with and without detrusor overactivity (DO) using a large database of overactive bladder (OAB) patients.

Methods

We reviewed the medical records of 513 women who underwent urodynamic studies for OAB symptoms without neurogenic or anatomical conditions that affect micturition function. Clinical symptoms were evaluated using a 3-day frequency-volume chart (FVC) including the Urinary Sensation Scale and American Urological Association Symptom Index (AUA-SI). All clinical and urodynamic findings were compared between women with and without DO.

Results

The patients’ mean age was 58.9 years. DO was identified urodynamically in 167 (32.6 %) women. Those with DO were older (62.9 vs 57.0 years, p?<?0.001); however, no differences in AUA-SI, episodes of daytime voiding, and episodes of nocturia were observed between the groups. Functional bladder capacity was smaller in women with DO; however, this difference did not reach statistical significance. Women with DO had significantly more urgency incontinence symptoms than those without DO (55.1 vs 29.5 %, p?<?0.001). In urodynamic parameters, the volumes at first desire to void and strong desire to void and maximum cystometric capacity were significantly smaller, and detrusor pressure at the opening was significantly higher in women with DO compared to subjects without DO (26.2 vs 21.2 cmH₂O, p?=?0.004).

Conclusions

Our findings suggest a more severe disturbance of bladder function when DO exists, although no differences were observed in symptom scores and 3-day FVC parameters among women with OAB symptoms according to the presence of DO.     

Therapie der ��beraktiven Blase

Background

Epidemiological data demonstrate an increasing prevalence of symptoms of overactive bladder (OAB) with age not only in women, but especially in men. Despite a comparable prevalence, however, men are still highly underrepresented in most large randomized studies on the effect of antimuscarinic drugs.

Question

In this subgroup analysis of the CAP Study the efficacy and tolerability of solifenacin was examined in 111 men with symptoms of OAB. The study was performed in a network between general practitioners and urologists under routine conditions over a period of 12 months.

Results

Treatment with solifenacin reduced all symptoms of OAB significantly, and the use of pads decreased by more than half. The tolerability of therapy was judged as ??excellent?? or ??good?? by over 95% of doctors and patients.

Conclusion

This subgroup analysis of the CAP Study confirms the good efficacy and tolerability of solifenacin in male OAB in daily practice over a treatment period of 1?year.     

Overactive bladder in diabetes mellitus patients: a questionnaire-based observational investigation

Purpose

Bladder dysfunction, secondary to diabetes, is mainly characterized by poor bladder emptying and overflow incontinence. However, there is evidence in literature that storage symptoms, as those suggestive for overactive bladder (OAB), may also affect people with diabetes. The aim of this study was to evaluate the prevalence of overactive bladder, the complaint of urinary urgency with/without urge incontinence, usually with frequency and nocturia, in people with diabetes compared to healthy subjects (control group).

Methods

Symptoms were assessed through the overactive bladder questionnaire (OAB-q), an investigative tool, specifically developed for OAB diagnosis.

Results

OAB-q scores resulted higher in diabetic people than those of the control group. Age and disease duration resulted in measurements that showed a statistical correlation with the OAB-q scores.

Conclusions

OAB symptoms are more prevalent in diabetic people than in non-diabetic people. This prompts further research to determine whether the onset of OAB symptoms can be considered as an indicator of diabetic neuropathy.     

Association of overactive bladder and C-reactive protein levels. Results from the Boston Area Community Health (BACH) Survey

Study Type – Aetiology (cohort) Level of Evidence 3a What's known on the subject? and What does the study add? Evidence of chronic inflammation in benign prostatic hyperplasia suggests a role of inflammation in the development of lower urinary tract symptoms. However, few studies have investigated the association of inflammation and overactive bladder in both men and women. Results of this population‐based study show a consistent association of increased C‐reactive protein levels with overactive bladder in both men and women. These results support the hypothesized role of inflammation in the development of overactive bladder.

OBJECTIVE

• ? To investigate the association between overactive bladder (OAB) and C‐reactive protein (CRP) in a population‐based sample of men and women.

SUBJECTS AND METHODS

• ? Epidemiological survey of urological symptoms among men and women aged 30–79 years. A multi‐stage stratified cluster design was used to randomly sample 5503 adults from the city of Boston. Analyses were conducted on 1898 men and 1854 women with available CRP levels.
• ? The International Continence Society defines OAB as ‘Urgency with or without urge incontinence, usually with frequency and nocturia.’ OAB was defined as: (1) urgency, (2) urgency with frequency, and (3) urgency with frequency and nocturia.
• ? Odds ratios (OR) and 95% confidence intervals (95% CI) of the CRP and OAB association were estimated using logistic regression.

RESULTS

• ? Prevalence of OAB increased with CRP levels in both men and women.
• ? In men, adjusted ORs (95% CI) per log₁₀(CRP) levels were 1.90 (1.26–2.86) with OAB defined as urgency, 1.65 (1.06–2.58) with OAB defined as urgency and frequency, and 1.92 (1.13–3.28) with OAB defined as urgency, frequency and nocturia.
• ? The association was more modest in women with ORs (95% CI) of 1.53 (1.07–2.18) for OAB as defined urgency, 1.51 (1.02–2.23) for OAB defined as urgency and frequency, and 1.34 (0.85–2.12) for OAB defined as urgency, frequency and nocturia.

CONCLUSIONS

• ? Results show a consistent association of increasing CRP levels and OAB among both men and women.
• ? These results support our hypothesis for the role of inflammation in the development of OAB and a possible role for anti‐inflammatory agents in its treatment.

     

Wirkung von Botulinumtoxin A in der ein- und mehrmaligen Behandlung der überaktiven Blase

Background

Quality of life (QoL) is negatively affected by the symptoms of overactive bladder (OAB). Standard treatment is the administration of anticholinergics, which are associated with nasty adverse effects. The aim of this prospective study was to evaluate the efficacy of singular and repeated botulinum-A toxin (BTX-A) injections in the bladder detrusor muscle in patients suffering nonneurogenetic OAB.

Results

Forty patients with OAB were treated with 500 mouse units of BTX-A (Dysport). Subjective satisfaction, micturition data, side effects, and the duration of effect were evaluated prospectively. The median follow-up was 9 months. The mean daily frequency decreased in 81% (p<0.001) of the patients, and nocturia decreased in 68% (p=0.009). The mean duration of effect until recurrence of OAB symptoms was 6 months. Using a visual analogue scale, subjective improvement in QoL was achieved in 83% of patients. Except for temporary urine retention in four cases, no severe side effects occurred.

Conclusion

The results of our prospective study show that the endoscopic application of BTX-A is a safe and highly effective treatment option for patients with OAB refractory to conventional treatment.     

Comparison of diary-derived bladder and sleep measurements across OAB individuals, primary insomniacs, and healthy controls

Introduction and hypothesis

Can diary-derived bladder and sleep measurements differentiate individuals with overactive bladder syndrome (OAB) from individuals with primary insomnia and healthy controls?

Methods

Bladder- and sleep-diary data were compared in nine OAB, ten insomnia, and five control individuals. One-way analysis of variance (ANOVA) was used for normally and Kruskal–Wallis test for nonnormally distributed variables, followed, when significant effects were found, by pairwise comparisons.

Results

OAB individuals woke up as frequently as insomniacs, but their awakenings were respectively shorter in duration (18.6 vs. 38.1 min.) and were predominantly initiated by nocturic events (89.2 vs. 23.9 % respectively). Regardless, their reported quality of sleep was as impaired as for the insomniacs. Furthermore, smaller mean volume voided awakenings were evident not only in those with OAB but also in insomniacs compared to controls.

Conclusions

Bladder- and sleep-diary data provide means to differentiate those with OAB from those with insomnia and healthy controls. Awakenings in OAB individuals were shorter than those with insomnia and much more likely due to the need to void. Thus, a reduction in the number of nocturic voids could be the most appropriate sleep-related outcome for nocturia therapy in individuals with OAB. In addition, limited nocturnal bladder capacity, though expected in OAB, was unexpectedly found in insomnia, possibly reflecting the role of consciousness (wakefulness at night) in modulating bladder sensation.     

The role of serum C-reactive protein in women with lower urinary tract symptoms

Introduction and hypothesis

Some lower urinary tract dysfunction (LUTD) subtypes may be associated with low-grade inflammation. This study aimed to investigate the role of serum C-reactive protein (CRP) levels in women with lower urinary tract symptoms (LUTS).

Methods

A total of 197 consecutive women with non-stress urinary incontinence (non-SUI) LUTS and 18 healthy women without LUTS (normal controls) were enrolled. LUTS include urinary storage, voiding, and post-micturition symptoms. Patients with previous bladder or urethral surgery, active urinary tract infections, or possible neurogenic lesions were excluded. Serum CRP levels were measured before any treatment was given. Patients were stratified to LUTD subgroups based on a 3-day voiding diary, uroflowmetry, and selective videourodynamic studies.

Results

Median CRP levels were significantly higher in women with overactive bladder (OAB) wet (i.e., with urgency incontinence, n?=?30, 0.12 mg/dl) than those in women with bladder oversensitivity (n?=?68, 0.075 mg/dl, P?=?0.008) and the control group (0.055 mg/dl, P?=?0.032). Further analysis revealed that body mass index and maximum flow rate were two independent factors that affected CRP levels. The area under the receiver-operating characteristic curve for using CRP to predict OAB wet was 0.55, and the most predictive cutoff point for CRP was 0.15 mg/dl (sensitivity 43.5 %, specificity 72.7 %).

Conclusions

High serum CRP levels were found in women with OAB wet, and they were related to lower maximum urinary flow rates and higher body mass indices in non-SUI LUTD. However, serum CRP is not a suitable biomarker for discriminating between subtypes of non-SUI LUTD.     

Transcutaneous electrical nerve stimulation: an effective treatment for refractory non-neurogenic overactive bladder syndrome?

Purpose

To assess the effect of transcutaneous electrical nerve stimulation (TENS) for treating refractory overactive bladder syndrome (OAB).

Patients and methods

A consecutive series of 42 patients treated with TENS for refractory OAB was prospectively investigated at an academic tertiary referral centre. Effects were evaluated using bladder diary for at least 48 h and satisfaction assessment at baseline, after 12 weeks of TENS treatment, and at the last known follow-up. Adverse events related to TENS were also assessed.

Results

Mean age of the 42 patients (25 women, 17 men) was 48 years (range, 18–76). TENS was successful following 12 weeks of treatment in 21 (50 %) patients, and the positive effect was sustained during a mean follow-up of 21 months (range, 6–83 months) in 18 patients. Following 12 weeks of TENS treatment, mean number of voids per 24 h decreased significantly from 15 to 11 (p < 0.001) and mean voided volume increased significantly from 160 to 230 mL (p < 0.001). In addition, TENS completely restored continence in 7 (39 %) of the 18 incontinent patients. Before TENS, all 42 patients were dissatisfied or very dissatisfied; following 12 weeks of TENS treatment, 21 (50 %) patients felt satisfied or very satisfied (p < 0.001). No adverse events related to TENS were noted.

Conclusions

TENS seems to be an effective and safe treatment for refractory OAB warranting randomized, placebo-controlled trials.     

Prospective and randomized comparison of electrical stimulation of the posterior tibial nerve versus oxybutynin versus their combination for treatment of women with overactive bladder syndrome

Objective

To verify whether the combination of transcutaneous electrical neural stimulation (TENS) with oxybutynin in the treatment of women with overactive bladder (OAB) would be more effective than isolated treatments.

Methods

We randomized 75 women with OAB, in three groups: GI—30 min TENS, twice a week; GII—daily slow release 10 mg oxybutynin; and GIII—TENS + oxybutynin (multimodal); all for 12 weeks. Patients were evaluated with validated questionnaires International Consultation on Incontinence-Short Form (ICIQ-SF), International Consultation on Incontinence-OAB (ICIQ-OAB), Symptom bother, and 3-day Voiding diary at weeks 0, 12, and 24.

Results

The groups were similar before treatment. After treatment, all groups significantly improved in OAB symptoms and quality of life (QoL). At week 12, ICIQ-OAB scores were 5.9, 4.6, and 2.9, in groups I, II, and III, respectively, p = 0.01. At week 24, GI and GIII kept the scores of the end of treatment (week 12), while GII increased ICIQ-OAB from 4.6 to 9.2, p = 0.0001, ICIQ-SF from 9.8 to 13.3, p = 0.0006, and Symptom bother score from 3.4 to 7.0, p = 0.0001.

Conclusions

The multimodal treatment was more effective and TENS alone or in association presented longer lasting results for improvement of clinical symptoms of OAB and QoL.     

Urinary nerve growth factor and a variable solifenacin dosage in patients with an overactive bladder

Introduction and hypothesis

We evaluated changes in urinary nerve growth factor (NGF) and NGF/creatinine (NGF/Cr) levels after increasing the dosage of solifenacin in overactive bladder patients.

Methods

The study groups included 59 overactive bladder (OAB) patients and 20 healthy subjects as controls. We measured NGF at baseline for the patients and controls, and used the Overactive Bladder Awareness Tool (OAB-V8) to evaluate urinary symptoms. All patients received a treatment of solifenacin 5 mg for 6 weeks. The responders to treatment served as group 1 and nonresponders received solifenacin 10 mg for an additional 6 weeks. Responders and nonresponders to the 10-mg treatment were defined as groups 2 and 3 respectively. NGF was measured after each treatment using the ELISA method and normalized by the urinary creatinine levels (NGF/Cr).

Results

There were 21, 22 and 16 patients in groups 1, 2, and 3 respectively. At baseline, the NGF and NGF/Cr levels were higher in groups 1, 2, and 3 compared with the controls. After the solifenacin 5 mg treatment, the NGF and NGF/Cr levels of group 1 individuals decreased to those of the control level. After increasing the dosage of solifenacin to 10 mg in group 2, the NGF and NGF/Cr levels decreased to normal levels. In group 3 (patients who did not responded to any treatment), these levels remained unchanged.

Conclusions

Our results suggest that urinary NGF could be a potential biomarker for monitoring the treatment of symptoms in OAB patients who are treated with solifenacin.

     

A retrospective comparison of ring pessary and multicomponent behavioral therapy in managing overactive bladder

Introduction and hypothesis

Overactive bladder (OAB) is a physically, psychologically, and socially disabling condition that affects millions of women worldwide and is especially prevalent postmenopause. The objective of our study was to compare the cure rates of ring pessary with those of multicomponent behavioral therapy in managing overactive bladder.

Methods

We performed a comparative retrospective parallel cohort study of all women whose overactive bladder was treated with multicomponent behavioral therapy or ring pessary over a 42-month period. At the end of the 6-month treatment period, cure was defined as the subjective (self-reported) absence of urinary urgency, frequency, nocturia, and urge incontinence in the preceding 30 days; the objective absence of these symptoms in a 7-day voiding diary; and a Patient Global Impression of Improvement response of “much better” or “very much better.”

Results

Ring pessary and multicomponent behavioral therapy had similar cure rates (29 out of 150 [19 %] vs 46 out of 231 [20 %] respectively, P?=?0.889; OR of 1.04, 95 % confidence interval 0.618–1.742, P?=?0.887). They also produced comparable cure rates in premenopausal (4 out of 31 [13 %] vs 14 out of 68 [21 %], P?=?0.358) and postmenopausal subjects (25/ out of 19 [21 %] vs 32 out of 163 [20 %], P?=?0.776), and in women who had undergone previous treatment (21 out of 108 [19 %] vs 31 out of 176 [18 %], P?=?0.699) and those who had not (8 out of 42 [19 %] vs 15 out of 55 [27 %], P?=?0.345). Logistic regression showed that neither treatment outcome is significantly associated with demographic characteristics; Pelvic Organ Prolapse Quantification at the anterior and posterior vaginal walls and at the vaginal cuff; previous treatment; overactive bladder symptoms; pad usage; or any combination thereof.

Conclusions

Ring pessary has a cure rate similar to that of multicomponent behavioral therapy in managing overactive bladder.     

Sustained effectiveness of percutaneous tibial nerve stimulation for overactive bladder syndrome: 2-year follow-up of positive responders

Introduction and hypothesis

The aim of the study was to describe effectiveness and safety of percutaneous tibial nerve stimulation (PTNS) at 2 years in women with overactive bladder (OAB) syndrome unresponsive to pharmacotherapy.

Methods

Of 30 women who had initial positive response to PTNS, 23 continued to receive maintenance treatment and were reassessed at 2 years using bladder symptom diaries and the Incontinence Impact Questionnaire (IIQ-7). They were also questioned on acceptability and any adverse effects of long-term peripheral neuromodulative treatment.

Results

Data from 23 women were available and 7 had been lost to follow-up. With maintenance treatment, the median nocturnal frequency at 2 years had decreased by 57 % (3.5 to 1.5 times/night), while the median IIQ-7 had reduced from 30.4 to 21.5 (both p?<?0.01) compared to pre-treatment baseline. Median nocturnal frequency and IIQ-7 scores at 2 years were comparable to those documented after initial response to treatment at 6 weeks, suggesting that maintenance therapy continued to suppress OAB symptoms. Daytime frequency and daily urgency incontinence episodes at 2 years were statistically similar to those documented at 6 weeks and remained lower than pre-treatment baseline (6.5 vs 11.8 and 2.0 vs 3.5, respectively, p?<?0.05). The women received a median of 8.42 treatments per year and the median length between treatments was 64.3 days. Apart from hypaesthesia in the toe of one responder lasting for 4 months, there were no reported side effects.

Conclusions

Women receiving PTNS for intractable OAB syndrome reported significant symptom relief at 2 years. This remains a safe mode of second-line treatment with excellent durability.