Increased extracellular matrix stiffness accompanies compromised bladder function in a murine model of radiation cystitis.

Radiation cystitis, a long-term bladder defect due to pelvic radiation therapy, results in lower urinary tract symptoms, such as urinary frequency and nocturia, suggestive of compromised bladder compliance. The goal of this study was to identify alterations to the mechanical behavior of the urinary bladder extracellular matrix of a murine model of radiation cystitis, at 3 and 6 months after radiation exposure. The results of this study demonstrated that the extracellular matrix of irradiated bladders was significantly less distensible when compared to age matching controls. These findings coincided with functional bladder changes, including increased number of voids and decreased voided volume. Both mechanical and functional changes were apparent at 3 months post-irradiation and were statistically significant at 6 months, demonstrating the progressive nature of radiation cystitis. Overall, the results of this study indicate that irradiation exposure changes both the mechanical and physiological properties of the bladder. STATEMENT OF SIGNIFICANCE: In humans, radiation cystitis results in lower urinary tract symptoms, such as urinary frequency and nocturia, suggestive of compromised bladder compliance. This pathology can significantly affect recovery and quality of life for cancer survivors. Gaining knowledge about how alterations to the mechanical behavior of the urinary bladder extracellular matrix can affect urinary function will have a significant impact on this population. The results of this study demonstrated that the extracellular matrix of irradiated bladders was significantly less distensible when compared to age matching controls, in a mouse model of radiation cystitis. These findings were accompanied by functional voiding changes, including increased number of voids and decreased voided volume. The results of this study uncovered that irradiation exposure changes the mechanical and physiological properties of the bladder.

Nocturia and electrocardiographic abnormalities among patients at an inner-city cardiology clinic.

AIMS: Nocturia has been increasingly recognized as a potential manifestation of cardiovascular disease. However, the relationship between nocturia and electrocardiographic (ECG) abnormalities has not been studied. This study aims to characterize the diagnostic utility of nocturia in identifying left ventricular hypertrophy (LVH), left atrial enlargement (LAE), and prolonged QTc on ECG. METHODS: Retrospective analysis of nocturnal voiding frequency and contemporaneous ECG data from consecutive patients evaluated at a university-based outpatient cardiology clinic. Three sets of three incremental binary multiple logistic regression models controlling for (1) age, (2) sex and race, and (3) body mass index, hypertension, diabetes mellitus, and diuretic utilization were performed to determine whether nocturia was predictive of LVH, LAE, and prolonged QTc. RESULTS: Included patients (n = 143, 77.6% nocturia) were predominantly African-American (89.5%), female (74.1%), and obese (61.5%), of whom 44.1%, 41.3%, and 27.3% had LVH, LAE, and prolonged QTc, respectively. Older age, African-American race, obesity, hypertension, diuretic use, LVH, and LAE were significantly associated with nocturia on univariate analysis. No significant differences were observed in the strength of associations between nocturia and LVH, LAE, or QTc prolongation based on age. Nocturia independently predicted LVH in Models I-III (odds ratios [ORs], 2.99-3.20; relative risks [RRs], 1.18 for all, p ≤ .046) and LAE in Models I-III (ORs, 4.24-4.72; RRs, 1.21 for all, p ≤ .015). No significant associations were observed between nocturia and prolonged QTc. CONCLUSIONS: Nocturia may be a risk marker for underlying structural cardiac abnormalities.

Low and high body mass index values are associated with female nocturia.

AIMS: We evaluated the relationship between body mass index (BMI), including low BMI, and nocturia in Japanese women. METHODS: We collected data on 18 952 women who participated in a multiphasic health screening in Fukui, Japan, in 2006. The participants were asked to report any current or previous disease. Self-reported current body weight and height were used to calculate the BMI. We analyzed the relationship between nocturia, as assessed by a questionnaire, and other variables including age, BMI, and comorbidities. RESULTS: The participants' mean age was 60.6 years. Overall, the prevalence of nocturia (two or more voids/night) was 4.3% and increased in an age-dependent manner. BMI did not affect nocturia in the young participants. The prevalence of nocturia was higher in the high-BMI women (>25.0 kg/m 2 ) in their fifth and sixth decades, but the prevalence was higher in the low-BMI (<18.5 kg/m 2 ) in the women more than 80-years old. A multivariate analysis revealed a significant association between nocturia and the following: age, BMI, sleep disturbance, arteriosclerosis, cerebrovascular disease, chronic pulmonary disease, diabetes mellitus, and hypertension. Not only high BMI (which is already reported as a risk of nocturia) but also low BMI was a factor related to nocturia. CONCLUSION: Our findings indicate that in addition to obesity, low BMI is a factor of nocturia in women.

Clinical characteristics of self-reported nocturia in patients with interstitial cystitis, and effects of bladder hydrodistention (with fulguration of Hunner lesions) on nocturia.

OBJECTIVE: The aim of this study was to investigate the clinical characteristics of nocturia in patients with interstitial cystitis (IC), and the effects of bladder hydrodistention (with fulguration of Hunner lesions) on nocturia. METHODS: The records of 81 patients who were diagnosed with IC were reviewed. Clinical characteristics were evaluated using the Interstitial Cystitis Symptom Index (ICSI), a visual analogue scale (VAS), and bladder diary data. Differences in characteristics between Hunner- and non-Hunner-type IC were compared. Correlations between nocturia and other clinical variables were assessed. Stepwise multiple regression analysis was performed to identify factors associated with nocturia. Further, changes in nocturia before and after hydrodistention (with fulguration of Hunner lesions) were analyzed. RESULTS: The mean (± SD) age of patients was 62.2 ± 15.3 years. Significant differences in nocturia were observed between Hunner- and non-Hunner-type IC. Nocturia was positively correlated with age, urgency score (ICSI and VAS), mean number of urgency episodes per 24 hours and the nocturnal polyuria (NP) index, and negatively correlated with average voided volume. Age, NP index, average voided volume, and the presence of Hunner lesions were independent factors associated with nocturia. Bladder hydrodistention significantly decreased nocturia in non-Hunner type IC without NP. In addition, regardless of the presence or absence of NP, bladder hydrodistention with fulguration of Hunner lesions significantly decreased nocturia in Hunner-type IC. CONCLUSIONS: The severity of nocturia is associated with age, NP, average voided volume, and the presence of Hunner lesions in IC patients. Bladder hydrodistention (with fulguration of Hunner lesions) has the potential to decrease nocturia.

Lack of Change in the Adaptation Ability of the Bladder for the Urine Production Rate in Aged Men with Nocturia.

INTRODUCTION: To investigate the association between bladder capacity and the urine production rate in aged men with or without nocturia using a frequency volume chart (FVC). MATERIALS AND METHODS: One-hundred and thirty-eight men aged 65-80 years were enrolled. After the International Prostate Symptom Score (IPSS) and 3 consecutive days FVC were evaluated, men were divided into 2 groups: Nocturia group, with any total IPSS, and ≥1.5 micturition on average at night; and Control group, with total IPSS < 8 and < 1.5 micturition on average at night. Each parameter was compared between the 2 groups using unpaired t tests. Linear and multiple regression analyses were performed between the urine production rate and volume/voids. RESULTS: Men numbering 45 and 21 were assigned to the Nocturia and Control groups respectively. There were no differences in background factors between the 2 groups. Volume/voids positively correlated with the urine production rate in both groups for day and night. A multivariate regression model also showed the same results. In the Control group, the degree of slope at night was higher than that during the day. However, in the Nocturia group, there were no differences in the degree of slope between day and night. CONCLUSIONS: This novel finding has led to a possibility for resolving nocturia.

Evidencia disponible acerca del uso del agonista B3- adrenoceptor selectivo mirabegrón para el tratamiento de la vejiga hiperactiva / Evidence available on the use of the selective B3- adrenoceptor agonist mirabegron for the treatment of overactive bladder

Contexto: Mirabegrón, agonista adrenoreceptor β3, supone el último desarrollo farmacológico para el tratamiento de la vejiga hiperactiva (VH).Objetivo: Presentar la evidencia disponible respecto a la eficacia y tolerancia de mirabegrón y discutir el potencial de dicho tratamiento en nuestro entorno. Adquisición de evidencia: Se revisan 11 estudios llevados a cabo con mirabegrón en pacientes con VH (2 fase II , 9 fase III ), todos en comparación con placebo y 6 de ellos incluyeron también tolterodina como brazo adicional. Se hace mayor énfasis en los principales ensayos fase III llevados a cabo en Europa, EE. UU. y Australia que evalúan la eficacia y seguridad a 12 semanas (NCT00662909, NCT00689104, NCT00912964) y la seguridad a 12 meses (NCT00688688). Se dispone también del análisis combinado de dichos estudios a 12 semanas, enfatizando en la eficacia global (FAS), la eficacia relativa a la incontinencia (FAS- I) y la seguridad (SAF). Más del 50% de los pacientes había abandonado previamente la medicación anticolinérgica para VH, lo que permite también obtener datos acerca de la efectividad de mirabegrón en pacientes tratados previamente con anticolinérgicos. Síntesis de evidencia: Mirabegrón es un fármaco eficaz que muestra una reducción estadísticamente significativa en número de episodios de incontinencia y en frecuencia miccional a partir de la 4.a semana, con mayor porcentaje tanto de pacientes secos como de pacientes con reducción ≥ 50% en número de episodios de incontinencia que placebo. La eficacia de mirabegrón 50 y 100 mg en la reducción en episodios de incontinencia sucede en pacientes nuevos y que han recibido antimuscarínicos, siendo la diferencia media ajustada y la mejora en la frecuencia miccional mayor en pacientes tratados. Su tolerancia es muy similar a placebo, particularmente para los efectos adversos de los antimuscarínicos (boca seca, estreñimiento y visión borrosa). Se aprecia un cambio mínimo no clínicamente significativo en la presión arterial sistólica, en la diastólica y en el pulso. Su eficacia se mantiene a largo plazo. Mirabegrón a dosis de 50 y 100 mg presenta mejoría frente placebo en la satisfacción del paciente, en la calidad de vida relacionada con la salud (HRQoL), en las molestias de síntomas y en la percepción del paciente de la condición vesical (PPBC). En el estudio europeo fase III a 12 semanas tolterodina proporcionó mejoría en menor medida que mirabegrón frente a placebo en la satisfacción del paciente, HRQoL, molestia de síntomas y PPBC (AU)

Context: Mirabegron, the selective β3-adrenoceptor agonist, heralds the latest development for the treatment of overactive bladder (OAB). Objective: To present the evidence available on the efficacy and tolerability of mirabegron and to discuss this treatment's potential in our setting. Evidence acquisition: We reviewed 11 studies conducted with mirabegron in patients with OAB (2 phase II, 9 phase III, all studies were compared to placebo with 6 studies also including tolterodine as an additional arm. Greater emphasis shall be given to the main phase III trials performed in Europe, the USA and Australia evaluating efficacy and safety after 12 weeks (NCT00662909, NCT00689104, NCT00912964) and safety after 12 months (NCT00688688). The combined analyses of these 12-week studies are also available, with emphasis on global efficacy (FAS), efficacy with regard to incontinence (FAS I ) and safety (SAF). More than 50% of patients had previously discontinued anticholinergics medication for OAB, thus allowing us to obtain data on the effectiveness of mirabegron in patients already treated with anticholinergics. Evidence synthesis: Mirabegron is an efficacious drug which presents a statistically significant reduction in the number of incontinence episodes and in urinary frequency as of 4 weeks, with a higher percentage of dry patients and a higher percentage of patients with reduction ≥50% in the number of incontinence episodes than placebo. The efficacy of mirabegron 50 and 100 mg in the reduction of incontinence episodes occurs in de novo patients and who have received antimuscarinics, with adjusted mean difference and improvement in urinary frequency greater in treated patients. Its tolerability is very similar to placebo particularly for the adverse effects of the antimuscarinics (dry mouth, constipation and blurred vision). A minimal, non-clinically significant change is observed in systolic and diastolic blood pressure and pulse. Its efficacy is long-term. Mirabegron at the doses of 50 and 100 mg presents an improvement versus placebo in patient satisfaction, health-related quality of life (HRQoL), symptom bother and patient's perception of bladder condition (PPBC). In the 12-week phase III European study tolterodine deliverred a lesser degree of improvement than mirabegron versus placebo in patient satisfaction, HRQoL, symptom bother and PPBC. Conclusions: Mirabegron is the first of a new class of compounds with a novel mechanism of action that is different to the antimuscarinics. It presents significant and clinically important efficacy in the treatment of the symptoms of OAB. It has advantages with regard to the results described by the patient in treatment satisfaction. Studies on its combined use with anticholinergics are ongoing (AU)

Does the presenting bladder volume at urodynamics have any diagnostic relevance?

The aim of this study is to assess the diagnostic relevance of the presenting bladder volume (PBV) at urodynamics in women. Its measurement is most accurately made by adding the voided volume at uroflowmetry and the postvoid residual. The study involved 1,140 women presenting for their initial urogynecological assessment. Multivariate analysis of the relationships between high or low PBVs and different clinical and urodynamic variables. Median PBV was 174 mL. In overall terms, women with lower PBVs (0-174 mL) are significantly more likely to be older, of lower parity (0-1), have the symptom of nocturia, and the final diagnoses of sensory urgency and detrusor overactivity. These women are significantly less likely to have posterior vaginal and apical vaginal prolapse. Women with higher PBVs (over 174 mL) are significantly less likely to have either bladder storage diagnoses. The relatively low median PBV might reduce the demonstration of clinical stress leakage and restrict the interpretation of uroflowmetry data.