Nocturnal Bladder Research Articles

PD37-01 TREATMENT OF NOCTURIA

INTRODUCTION AND OBJECTIVE: This study aims to assess the efficacy of behavioral modification alone vs. combined behavioral modification with traditional first-line pharmacologic treatments in reducing nocturnal voiding frequency among men with nocturia. METHODS: Retrospective analysis of voiding diaries completed by patients treated for lower urinary tract symptoms (LUTS) at a Veterans Affairs urology clinic was performed. Diaries were abstracted for 24-h total volume, nocturnal urine volume (NUV), and actual number of nocturnal voids (ANV). Patients were included if they were male, ≥18 years, had ≥1 nocturnal void(s) on baseline diary, and a follow-up diary within 365 days of baseline. Patients were deemed to have experienced improvement if ANV decreased by ≥1 voids(s) from baseline to follow-up. RESULTS: 321 voiding diaries (176 diary pairs) were analyzed from 98 unique patients who met the inclusion criteria. Mean duration from baseline to follow-up was 181 days. Improvement was observed in 67 diary pairs (mean improvement -1.76 [±1.07] voids); no change was observed in 44 diary pairs, and 65 demonstrated an increase in ANV (+1.86 [±1.91] voids). Among those who improved, baseline ANV was significantly greater (3.5 vs. 2.1 voids, p<0.001), and baseline post-void residual (PVR) volume was lower (45.7 vs. 89.3, p=0.03). No other differences were observed in standard diary parameters. Improvement in ANV was accompanied by a significant decrease in 24-h volume (-344 mL, p=0.01), NUV (-262 mL, p<0.001), and an increase in first uninterrupted sleep period (FUSP) duration (+1.92 hours, p<0.001). Patients prescribed behavioral modification + 1 or more pharmacologic agent were no more likely to improve than patients prescribed lifestyle modification alone. Irrespective of pharmacotherapy status, improvement was accompanied by significant decreases in ANV, total 24-h voids voids, nocturnal bladder capacity index (NBCi), and nocturia index (Ni), as well as increased FUSP (Table). CONCLUSIONS: In this study, no significant difference was observed in nocturia severity between patients treated with behavioral modification alone vs. combined behavioral modification + pharmacologic agent(s). Alternative pharmacologic options may be needed to expand the urologist’s toolkit beyond an initial individualized lifestyle modification plan in the management of nocturia.Source of Funding: None

Prevalence, subtypes, and correlates of nocturia in the symptoms of Lower Urinary Tract Dysfunction Research Network cohort.

We determined the prevalence, severity, and correlates of nocturia in a large clinical cohort of patients. Patients presenting with lower urinary tract symptoms (LUTS) completed 3-day bladder diaries. Nocturia was quantified based on the mean number of nighttime voids documented over the 3 days. Nocturia subtypes (global polyuria, nocturnal polyuria [NP], reduced global bladder capacity, and reduced nocturnal bladder capacity) were assessed. Bother due to nocturia was measured by the LUTS Tool. Sleep quality was assessed with the Patient-Reported Outcomes Measurement Information System Sleep Scale. Multivariable multinomial regression was used to explore patient characteristics associated with nocturia. In 502 participants with analyzable diaries (285 men and 217 women), the mean number of nocturia episodes over 3 days was 0 in 103 (20.5%), >0 to <1 in 151 (20.1%), 1 to <2 in 165 (32.9%), and ≥2 in 83 (16.5%). Sixty-seven percent of the participants with nocturia ≥1 reported significant bother from their nocturia. NP was the most common nocturia subtype and was present in 17% of those with nocturia = 0, 40% of those with nocturia >0 to <1, 65% of those with nocturia 1 to <2%, and 77% with nocturia 2+. Higher degrees of nocturia were associated with male sex, greater sleep disturbance, and a higher likelihood of exhibiting multiple nocturia subtypes. Nocturia ≥1 occurred in 49% of LUTS patients and caused significant bother in the majority of them. The most common subtype was NP, but a substantial proportion of patients exhibited additional characteristics.

SENS-U: continuous home monitoring of natural nocturnal bladder filling in children with nocturnal enuresis – a feasibility study

Enuresis is a common problem in children. One treatment option is a wetting alarm that provides an alarm when incontinence occurs. A drawback of this approach is that the child is still awakened by wet sheets. Recently, a wearable, wireless ultrasonic bladder sensor became available, the SENS-U, which has the potential to prevent the enuretic event by waking up the child before the bladder is full. In this first feasibility study, the aim is to perform a night-time, home-based evaluation of the SENS-U in children with monosymptomatic nocturnal enuresis (MNE). In this study, children (6-12years) with MNE were included for a one-night monitoring session. During the night, the SENS-U continuously (i.e. every 30s) estimated the filling status [notifications were deactivated]. In addition, urine volume was collected in a measurement cup (or diaper weight). The total measured natural nocturnal bladder filling (NNBF) cycles was analyzed by descriptive statistics. Before and after the measurement, sleep behavior was assessed by a selection of the Children's Sleep Habits Questionnaire. Fifteen patients (boys/girls: 13/2) [mean age: 8.6±1.5years] have been enrolled. One patient was excluded due to inadequate sensor-to-skin contact. For 14 children, 18 NNBF cycles were recorded (voiding diary) of which three patients (21%) had more than one NNBF cycle. The SENS-U was able to successfully detect 83% of the NNBF cycles. The three missed NNBF cycles had a voided volume ≤30ml, which was at the lower limit of the sensor's detection range. The SENS-U had no effect on sleeping behavior. The SENS-U was able to monitor the natural nocturnal bladder filling successfully in children with monosymptomatic nocturnal enuresis at home, without disturbing their sleep. Future research focuses on investigating the usability of the SENS-U for both diagnostic - and treatment purposes.

Beyond the bladder: poor sleep in women with overactive bladder syndrome

Nocturnal bladder symptoms and sleep disruption commonly coexist in middle-aged and older women. Although sleep disruption is often attributed to nocturnal bladder symptoms in women with overactive bladder syndrome, nonbladder factors also may influence sleep in this population. Many women with overactive bladder are eager to identify nonpharmacologic strategies for both bladder symptoms and sleep disruption, given the potential adverse effects of sedative and anticholinergic bladder medications in this population. To provide greater insight into the complex relationship between nighttime overactive bladder symptoms and sleep disruption, and to evaluate the effects of a guided slow-paced respiration intervention on sleep outcomes in women with overactive bladder. We conducted an ancillary study within a randomized trial of slow-paced respiration in women with overactive bladder symptoms. Ambulatory community-dwelling women who reported ≥3 episodes/day of urgency-associated voiding or incontinence were randomized to use either a portable biofeedback device (RESPeRATE; Intercure, Ltd) to practice guided slow-paced respiration exercises daily for 12 weeks (N=79) or an identical-appearing device programmed to play nonrhythmic music without guiding breathing (N=82). At baseline and after 12 weeks, bladder symptoms were assessed by voiding diary, sleep duration, and disruption were assessed by sleep diary corroborated by wrist actigraphy, and poor sleep quality was determined by a Pittsburgh Sleep Quality Index global score >5. Of the 161 women randomized, 31% reported at least twice-nightly nocturia, 26% nocturnal incontinence, and 70% poor sleep quality at baseline. Of the 123 reporting any nighttime awakenings, 89% averaged 1 or more nighttime awakenings, and 83% attributed at least half of awakenings to using the bathroom. Self-reported wake time after sleep onset increased with increasing frequency of nocturnal bladder symptoms (P=.01 for linear trend). However, even among women without nocturia, average sleep quality was poor (Pittsburg Sleep Quality Index global score mean of 7.3; 95% confidence interval, 6.0-8.6). Over 12 weeks, women assigned to slow-paced respiration (N=79) experienced modest improvements in mean nocturnal voiding frequency (0.4 fewer voids/night), sleep quality (1.1 point score decrease), and sleep disruption (1.5% decreased wake time after sleep onset). However, similar improvements were detected in the music control group (N=81), without significant between-group differences. Many women with overactive bladder syndrome experience disrupted sleep, but not all nocturnal awakenings are attributable to bladder symptoms, and average sleep quality tends to be poor even in women without nocturia. Findings suggest that clinicians should not assume that poor sleep in women with overactive bladder syndrome is primarily caused by nocturnal bladder symptoms. Guided slow-paced respiration was associated with modest improvements in nocturia frequency and sleep quality in this trial, but the results do not support clinician recommendation to use this technique over other behavioral relaxation techniques for improving sleep.

P.822 Prevalence of mental disorders among juvenile offenders: Systematic review and meta-analysis

Enuretic children wet their beds either because of nocturnal polyuria or nocturnal detrusor overactivity. Polyuric children often respond to desmopressin, whereas children with nocturnal detrusor overactivity are often therapy resistant and may have low daytime voided volumes. It is logical to assume that the enuretic event in children with nocturnal polyuria occurs with a full bladder, i.e. with the enuretic voided volume (EVV) close to the child's expected bladder capacity (EBC) for his/her age. However, the EVV has only rarely been studied, and little is known about how it relates to case history, polyuria, or daytime bladder function. The aim of this study was to look at EVV and relate it to voiding chart data and treatment response.Anamnestic data and voiding charts, including measurement of nocturnal urine production and EVV, in enuretic children with or without concomitant daytime incontinence attending a tertiary center were retrospectively reviewed. The EVV was analyzed and compared to anamnestic data, voiding chart data, and response to therapy in accordance with the guidelines of the International Children's Continence Society.Data were available for 220 children (age 5–24, median 9), 40 of whom were girls. The prevalence of previous or present daytime incontinence was 42.4%, and 50.5% sometimes experienced urgency. The average EVV was 54.9 ± 32.8% of EBC. EVV correlated highly significantly to nocturnal urine production (p < 0.001). Still, EVV ≥ EBC was observed in only 16 children. EVV was slightly larger in girls (p = 0.013) and in children with urgency (p = 0.034), but there were no significant EVV differences between children responding or not responding to antidiuretic, anticholinergic, or antidepressant therapy. Relevant data are summarized in the Table below.Case history and daytime voiding chart data give very little information about nocturnal bladder function. The EVV is strongly influenced by nocturnal urine production but only rarely reaches up to a level close to or exceeding the EBC. The enuretic event only very rarely represents the emptying of a full bladder. Thus, a component of nocturnal detrusor overactivity can be assumed to be present in almost all enuretic children, even in children with nocturnal polyuria. The value of the EVV is limited in predicting response to therapy.

S839 PHASE II STUDY OF ORAL RIGOSERTIB COMBINED WITH AZACITIDINE IN PATIENTS WITH HIGHER‐RISK MYELODYSPLASTIC SYNDROMES (MDS)

Background:Azacitidine based combination trials have not demonstrated improved response or outcome over single agent azacitidine (Sekeres JCO 2017; Ades ASH 2018). Results of a Phase I/II study in MDS patients demonstrated oral rigosertib and standard‐dose azacitidine to be well‐tolerated with efficacy in HMA‐naive and HMA‐failure patients: at 560 mg qAM/280 mg qPM rigosertib dosing, overall response rate (ORR) was 77%; 88% for HMA‐naive group, 60% for HMA‐failure group. An increase in genitourinary (GU) adverse events was noted with the combination. Rigosertib at higher doses (1120 mg/day) yielded maximum ORR in lower‐risk MDS and was thus investigated in additional cohorts (Raza ASH 2017). Risk‐mitigation strategies were employed to reduce GU AEs (Navada ASH 2018).Aims:‐Methods:Oral rigosertib was administered on Day 1–21 of a 28‐day cycle (840 mg or 1120 mg total); parenteral (SC or IV) azacitidine 75 mg/m2/day was given for 7 days starting on Day 8 in patients with MDS including both HMA naive and HMA failures.Results:Of those patients receiving ≥840 mg rigosertib, 55 were evaluable for response. 26 were treated with 840 mg rigosertib and 29 were treated with 1120 mg.Median duration of response was 12.2 months (range, 0.1–24.2+) and 10.8 months (range, 0.1–11.8+) for HMA naive and HMA‐failure pts, respectively. Median number of cycles to initial/best response was 1/4 and 2/5, respectively.Responses per IWG 2006 occurred in all IPSS‐R subgroups. In low/intermediate (N = 17), CR occurred in 4 (24%), PR was 0, mCR was 5 (29%), stable disease was 2 (12%), progression was 0, not evaluable was 3 (18%), HI in 9 (53%). In high risk (N = 23), CR occurred in 2 (9%), PR in 1 (4%), mCR was 8 (35%), stable disease was 6 (26%), progression was 1 (4%), not evaluable was 4 (17%), and HI in 7 (30%). In very high risk (N = 33), CR occurred in 5 (15%), PR was 0, mCR was 10 (30%), stable disease was 2 (6%), progression was 4 (12%), not evaluable was 11 (33%), and HI in 11 (33%).The following Safety‐optimization strategies were employed to minimize genitourinary toxicities of hematuria and dysuria: Second rigosertib dose must be taken at 3 PM (±1 hour) at least 2 hours after lunch to avoid a nocturnal bladder dwell time (Maniar M, et al. ASCO 2018 Sub for Pub) Oral hydration of at least two liters of fluid per day is encouraged Mandatory bladder emptying prior to bedtime Urine pH approx. 2 hours after AM dose. Sodium bicarbonate suggested 650 TID if pH &lt; 7.5 Summary/Conclusion:Oral rigosertib with azacitidine demonstrated efficacy in HMA‐naive patients. The combination markedly improved hematopoiesis and reduced blasts in HMA‐failure patients. The combination was well‐tolerated in repetitive cycles for 25+ months. Risk mitigation strategies reduced urinary AEs in the expansion cohort. A pivotal Phase 3 trial is planned in an HMA‐naive patient population.image

Study on resting-state cerebral functional magnetic resonance imaging and ambulatory urodynamics monitoring in children with primary monosympt-omatic nocturnal enuresis

Objective To investigate the significance of blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI) and ambulatory urodynamics monitoring (AUM) to find the cause of primary monosymptomatic nocturnal enuresis (PMNE) in children. Methods Thirty-seven children with PMNE (20 males and 17 females) were selected, with a mean age of (11.3±4.1) years old.A clinical management tool, 3-day urination record, daytime BOLD-fMRI scan, conventional urodynamics (CUD) and AUM were performed respectively.Thirty-seven gender-age matched children(19 males, 18 females) who would receive surgery treatment because of upper urinary tract disease and were confirmed to have no lower urinary tract dysfunction by CUD were enrolled as controls, with a mean age of (11.1±2.9) years old, and 13 cases underwent BOLD-fMRI scanning. Results It was found that the ALFF value of the left middle frontal gyrus of PMNE was decreased and the ReHo value of the left superior occipital gyrus was increased compared with the control group by the resting BOLD-fMRI.The maximum voiding volume of PNME children was (303.11±87.48) mL, the total urine volume at night was (568.65±208.48) mL, and the nighttime bladder volume was (217.43±81.53) mL.The incidence of maximum voiding volume reduction, nocturnal polyuria and decreased nocturnal bladder volume were 24.32% and 56.76%, and 64.86%, respectively.However, AUM results showed that maximum detrusor pressure in the PMNE group was (39.22±7.78) cmH2O(1 cmH2O=0.098 kPa), which was statistically significantly higher than that in CUD (32.22±9.00) cmH2O, and the difference was statistically significant (P 0.05). Conclusions The abnormal functions of the left middle frontal gyrus and left superior occipital gyrus, nighttime DO and the decrease of bladder capacity at night are considered to be key causes of enuresis in children with PMNE.AUM and resting state BOLD-fMRI evaluations are helpful in differentiating the pathogenesis of PMNE. Key words: Enuresis; Ambulatory urodynamics monitoring; Functional magnetic resonance imaging; Resting state

Classification of nocturia by analyzing frequency volume chart and relations with international prostate symptom score in male patients with lower urinary tract symptoms in Korea

PurposeTo evaluate the categories of nocturia and relationships with the international prostate symptom score (IPSS) in Korean men with lower urinary tract symptoms (LUTS) accompanying nocturia.Materials and MethodsFive hundred twenty-one male patients from five different hospitals, aged ≥18 years, were included. The 3-day frequency volume chart was used to identify nocturia. We also used the IPSS and The International Consultation on Incontinence Modular Questionnaire-Nocturia (ICIQ-N) module to verify the correlation between nocturia and quality of life.ResultsThe distribution of nocturia events varied from 1 to 11, and 2 nocturia events were most prevalent (48.4%). Across the various numbers of nocturia events, the mean age, first sleep period, functional bladder capacity (FBC), nocturnal polyuria index (NPI), nocturia index (NI), predicted number of nightly voids, and nocturnal bladder capacity index (NBCI) were statistically different. Patients with pure nocturnal polyuria showed different night lengths, nocturnal urine volume, FBC, NPI, NI, and predicted number of nightly voids than those without nocturnal polyuria. Patients with severely reduced NBCI were prominent in the IPSS >20 group, and the degree of vexation increased with the number of nocturia events. The IPSS storage symptom score and ICIQ-N symptom score positively correlated with nocturia events.ConclusionsIn Korean male LUTS patients with nocturia, mixed-type nocturia was prominent, and patients with a high IPSS had a much poorer sleep quality than those with a low IPSS.

Effectiveness of Intra-anal Biofeedback and Electrical Stimulation in the Treatment of Children With Refractory Monosymptomatic Nocturnal Enuresis: A Comparative Randomized Controlled Trial.

PurposeTo compare the effects of intra-anal biofeedback (BF) and intra-anal electrical stimulation (ES) on pelvic floor muscles (PFMs) activity, nocturnal bladder capacity, and frequency of wet night episodes in children with refractory primary monosymptomatic nocturnal enuresis (PMNE).MethodsNinety children of both sexes aged 8–12 years with refractory PMNE participated in this study. They were randomly assigned to 3 groups of equal number: control group (CON) that underwent behavioral therapy and PFM training, and 2 study groups (BF and ES) that underwent the same program in addition to intra-anal BF training and intra-anal ES, respectively. PFMs activity was assessed using electromyography, nocturnal bladder capacity was evaluated by measuring the first morning voided volume, and a nocturnal enuresis diary was used for documenting wet night episodes before treatment and after 3 months of treatment.ResultsAfter training, all groups showed statistically significant improvements in all measured outcomes compared to their pretreatment findings. The ES group showed significantly greater improvements in all measured outcomes than the CON and BF groups.ConclusionsBoth intra-anal BF training and ES combined with behavioral therapy and PFMs training were effective in the treatment of PMNE, with intra-anal ES being superior to BF training.

Amelioration of Rigosertib Treatment Related Genitourinary (GU) Adverse Events (AEs) in Patients with Myelodysplastic Syndromes: Implementation of Novel Dosing Regimen Derived through Pharmacokinetic Modeling in Phase 2 Study of Oral Rigosertib in Combination with Azacitidine

Introduction: Rigosertib is a small molecule inhibitor of cellular signaling pathways in cancer cells by acting as a Ras mimetic. The inhibitory effect is mediated by Rigosertib binding to the Ras-binding domain found in many Ras effector proteins (Athuluri-Divakar SK, Cell 2016). Oral administration of Rigosertib was initially evaluated in lower risk MDS patients. The drug, administered as 560 mg BID (q12hr; 2/3 wks), was associated with high rates of transfusion independence but with significant GU AEs (Raza, et al, Blood 2017 130:1689). Subsequently, a reduction in the PM dose to 280 mg led to a decrease in GU AEs, suggesting a causal relationship with nocturnal bladder drug concentration. When oral administration of Rigosertib was tested with standard dose of parenteral Azacitidine in a Phase I/II trial (NCT01926587) at a dose of 560/280 mg (Q12hrs, 3/4 weeks), the ORR was 77%; with 60% for the HMA relapsed/refractory group for the high risk MDS patients. The impressive response rate, in the combination treatment, was also associated with significant GU AEs. Hence, it is important to understand the underlying cause and devise ways to maximize response rates with minimization of GU AEs.Previously, it was established that GU AEs were unlikely to be related to the higher systemic exposure of the drug (Maniar, et al ASH 2018, Abstract submitted) but attributed to the nocturnal dwell time of high drug concentration in the bladder of patients treated with continuous oral administration (3/4 weeks). In this investigation, we developed a pharmacokinetic model to simulate the systemic and bladder exposure of Rigosertib after repeated oral dosing. The overall aim was to identify and implement an oral dosing regimen for Rigosertib that would maximize the systemic exposure with minimization of nocturnal bladder concentration, thereby potentially mitigating or eliminating the GU AE's.Methods: A 2-compartment model with 1st order absorption and elimination (Figure 1) was fitted to data collected from patients with solid malignancies at a 560 mg dose (n=25). Model parameter estimates were then used to generate a virtual population of 100 patients. Each virtual patient was randomly assigned parameter values based on the 95% confidence interval for each parameter estimate obtained through the modeling analysis. Model simulations were then performed to evaluate the steady state systemic and urinary exposure of Rigosertib in the virtual population after treatment with different dosing schedules (Figure 2). Besides plasma exposure (Cmax, AUC), the predicted rigosertib bladder concentration during the sleep-cycle was also assessed. From this analysis, optimal dosing regimens were selected for evaluation in a Phase 2 study in HR-MDS patients in combination with Azacitidine. The model was validated by comparing the predicted systemic exposure with observed data using these optimal dosing regimens, and by comparing Grade 3 GU AE's events from the pre- and post-optimization of dosing regimen (NCT01926587).Results: The model-predicted steady state plasma concentration-time profile of Rigosertib for different dosing regimens is shown in Figure 3. The duration of exposure of drug above minimum effective concentration (MEC, 0.175 ug/ml) was not changed by varying the dosing regimen. Importantly, model simulations demonstrated that BID dosing, with the dosing interval of 8 hours, would reduce the bladder concentration of Rigosertib by as much as 70% during sleep without compromising systemic drug exposure (Table 1). As illustrated in Table 2, model simulated Rigosertib exposure (Cmax, AUC) compared favorably with data from patients treated with the novel twice daily dosing regimens (560mg/560mg and 840 mg/280mg, dosing interval of 8 hours), thereby validating the model. Preliminary safety data from the on-going trial demonstrates that the Grade 3 GU AEs were significantly reduced (12%) with the optimized dosing regimen compared to the pre-optimized dosing regimen (29%) despite using a higher total dose of drug (1120 mg vs 840 mg).Conclusions: This study demonstrates the utility of pharmacokinetic modeling for designing a dosing regimen directed at reducing the incidence of toxicity. The identified dosing regimen, along with mitigation strategies, successfully reduced the risk of Grade 3 GU AEs of rigosertib without compromising the duration of systemic exposure of Rigosertib above MEC in HR MDS patients. [Display omitted] DisclosuresTaft:Onconova Therapeutics, Inc: Research Funding. Ren:Onconova Therapeutics, Inc: Employment, Equity Ownership. Zbyszewski:Onconova Therapeutics, Inc: Employment, Equity Ownership. Morgan:Onconova Therapeutics, Inc: Consultancy. Petrone:Onconova Terapeutics Inc.: Employment, Equity Ownership. Fruchtman:Onconova Therapeutic Inc: Employment, Equity Ownership. Maniar:Onconova Therapeutics, Inc: Employment, Equity Ownership.

Etiology of nocturia response in men with diminished bladder capacity.

To test the hypothesis that patients with nocturia owing to diminished global or nocturnal bladder capacity improve via increased bladder capacity. This is a retrospective analysis of voiding diaries completed at a VA urology clinic between 2008-2017. Inclusion required patients aged at least 18 years, male, undergoing treatment for nocturia, and having completed at least two 24-hour voiding diaries ≥1 month apart. Patients were divided into two cohorts: responders (any decline in nocturia) and non-responders (no change or any increase in nocturia). Patients were further sub-stratified as having low global bladder capacity (maximum voided volume [MVV] <200 mL) versus low nocturnal bladder capacity (nocturnal maximum voided volume [NMVV] <200 mL and MVV ≥200 mL). Wilcoxon rank-sum was applied with a Bonferroni correction to test significance. Forty pre- and post-treatment diaries from 27 patients, and 19 pre- and post-treatment diaries from 17 patients were identified as having low global and low nocturnal bladder capacity, respectively. Nocturia responders with low global bladder capacity demonstrated significant decline compared to non-responders in nocturnal urine volume (NUV) (-140 vs +75, P < 0.01) and nocturnal bladder capacity index (NBCi) (-0.59 vs +0.23, P < 0.01). Patients with low nocturnal bladder capacity similarly demonstrated decreased NUV (-30 vs +160, P = 0.04) and NBCi (-1.4 vs +0.33, P < 0.01). There was no significant change in MVV or NMVV for either group. Treatment directed at lowering nocturnal urine production and enabling patients to consistently void at capacity is a rational strategy to treat nocturia in patients with low bladder capacity.

The amount of urine voided in bed by children with enuresis

Enuretic children wet their beds either because of nocturnal polyuria or nocturnal detrusor overactivity. Polyuric children often respond to desmopressin, whereas children with nocturnal detrusor overactivity are often therapy resistant and may have low daytime voided volumes. It is logical to assume that the enuretic event in children with nocturnal polyuria occurs with a full bladder, i.e. with the enuretic voided volume (EVV) close to the child's expected bladder capacity (EBC) for his/her age. However, the EVV has only rarely been studied, and little is known about how it relates to case history, polyuria, or daytime bladder function. The aim of this study was to look at EVV and relate it to voiding chart data and treatment response. Anamnestic data and voiding charts, including measurement of nocturnal urine production and EVV, in enuretic children with or without concomitant daytime incontinence attending a tertiary center were retrospectively reviewed. The EVV was analyzed and compared to anamnestic data, voiding chart data, and response to therapy in accordance with the guidelines of the International Children's Continence Society. Data were available for 220 children (age 5-24, median 9), 40 of whom were girls. The prevalence of previous or present daytime incontinence was 42.4%, and 50.5% sometimes experienced urgency. The average EVV was 54.9±32.8% of EBC. EVV correlated highly significantly to nocturnal urine production (p<0.001). Still, EVV≥EBC was observed in only 16 children. EVV was slightly larger in girls (p=0.013) and in children with urgency (p=0.034), but there were no significant EVV differences between children responding or not responding to antidiuretic, anticholinergic, or antidepressant therapy. Relevant data are summarized in the Table below. Case history and daytime voiding chart data give very little information about nocturnal bladder function. The EVV is strongly influenced by nocturnal urine production but only rarely reaches up to a level close to or exceeding the EBC. The enuretic event only very rarely represents the emptying of a full bladder. Thus, a component of nocturnal detrusor overactivity can be assumed to be present in almost all enuretic children, even in children with nocturnal polyuria. The value of the EVV is limited in predicting response to therapy.

Evidence of reduced bladder capacity during nighttime in children with monosymptomatic nocturnal enuresis

Bladder capacity in children with nocturnal enuresis is assessed by maximal voided volumes (MVV) obtained through daytime frequency volume (FV) charts. Although a degree of association has been demonstrated, daytime MVV does not consistently correspond with the nocturnal bladder capacity (NBC) in monosymptomatic nocturnal enuresis (MNE). It was hypothesized that isolated reduced NBC is a common phenomenon in children with nocturnal enuresis, despite normal daytime bladder function. The aim of this study was to evaluate NBC in children with MNE and normal daytime voided volumes. Specifically, it aimed to determine the prevalence and degree of reduced NBC when using nocturnal urine production (NUP) during wet nights as a surrogate estimate of NBC. Furthermore, it aimed to investigate the relationship between NBC and desmopressin response. Data from 103 children aged 5-15 years consecutively treated for MNE in a tertiary referral centre and with normal MVV on daytime FV charts were collected for this cohort study. Home recordings were completed for 2weeks at baseline and during desmopressin dose titration. Estimated nocturnal bladder capacity (eNBC) was assessed separately each night as the total NUP causing a wet night. If NUP during a wet night was less than MVV, it was considered to be reduced eNBC during that particular night. Surprisingly, 82% (n=84) of the children with MNE and normal daytime MVV experienced at least one wet night, with NUP below the daytime MVV indicative of a reduced eNBC. For 84 patients, mean percentage of wet nights with reduced eNBC (NUP below MVV) was 49% (SD±31). A total of 11% of children with frequently reduced eNBC (>40% of wet nights with reduced eNBC) responded to desmopressin (Summary Fig.). Of the children with frequently reduced NBC, 91% experienced wet nights, with NUP <65% of expected bladder capacity (EBC). A significant proportion of children with MNE and normal MVV during the daytime frequently experienced wet nights, with a NUP well below their MVV and even <65% of EBC. This indicated that bladder reservoir dysfunction during sleep is relatively common in MNE. This abnormality was not reflected on daytime recordings, and thus nighttime data with NUP must be collected. This phenomenon may explain treatment failure to desmopressin, despite adequate antidiuretic response.

Fesoterodine for the Treatment of Nocturnal Urgency in Patients with Overactive Bladder Syndrome: An Analysis of Responders and Nonresponders

A recent study demonstrated improvement in nocturnal urgency in patients with overactive bladder when treated with fesoterodine. In the current study we aimed to determine which bladder diary parameters predict the response to fesoterodine in these patients. Patients with nocturnal urgency completed a 2-week, single-blind placebo run-in followed by 1:1 double-blind randomization to 12 weeks of fesoterodine or placebo. We analyzed bladder diary parameter changes from baseline to week 12, including the actual number of night voids (total number of nocturia episodes), maximum voided volume, nocturnal bladder capacity, Nocturnal Bladder Capacity Index (NBCi) (actual number of night voids - nocturnal urine volume/maximum voided volume - 1), nocturnal urine volume, the nocturia index (nocturnal urine volume/maximum voided volume) and the nocturnal polyuria index (nocturnal urine volume/24-hour volume). Additionally, we analyzed OAB-q (Overactive Bladder Questionnaire) changes. There was a linear relationship between the likelihood of being a responder for NBCi and the nocturia index. Responders had a significant decrease in nocturnal urine volume relative to baseline (-181.7 ml, p <0.01). Neither group showed a significant change in maximum voided volume relative to baseline. There was a significant decrease in NBCi and the nocturia index in responders (-0.82 and -0.61, respectively, each p <0.01). Responders demonstrated improvement in the OAB-q concern, coping, sleep, bother and total score metrics. Patients with nocturnal urgency secondary to overactive bladder syndrome and low nocturnal bladder capacity with a mismatch between nocturnal urine production and bladder capacity may benefit from fesoterodine. Symptom improvement appears to be mediated by increases in typical rather than maximum nocturnal voided volumes. Symptom improvement was associated with improved quality of life.

MP36-13 CHANGES IN NOCTURNAL BLADDER DIARY PARAMETERS IN MEN AFTER URETHROPLASTY FOR ANTERIOR URETHRAL STRICTURES

You have accessJournal of UrologyTrauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) I1 Apr 2017MP36-13 CHANGES IN NOCTURNAL BLADDER DIARY PARAMETERS IN MEN AFTER URETHROPLASTY FOR ANTERIOR URETHRAL STRICTURES Rajveer Purohit, Jyoti D. Chouhan, frank copeli, Dennis Robins, Andrew Tam, and Jeffrey P Weiss Rajveer PurohitRajveer Purohit More articles by this author , Jyoti D. ChouhanJyoti D. Chouhan More articles by this author , frank copelifrank copeli More articles by this author , Dennis RobinsDennis Robins More articles by this author , Andrew TamAndrew Tam More articles by this author , and Jeffrey P WeissJeffrey P Weiss More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1124AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We evaluated changes in nocturnal voiding patterns of men before and after anterior urethroplasty for urethral stricture disease using a pre-operative and post-operative 24 hour bladder diary. METHODS This was a retrospective study of men undergoing anterior urethroplasty for urethral stricture who completed a pre-operative and post-operative 24 hour bladder diary. Diaries done anytime prior to surgery and at least 1 month after surgery were included. Patients recorded the volume, time of void and degree of urgency of voids. Paired t-tests were performed on nocturnal voiding variables. RESULTS 18 men had preoperative and post-operative 24 hour bladder diaries. The mean age was 45.4 years (median 46.5,range, 26-70). 13 strictures were bulbar (72.2%), 4 pendulous-bulbar (22.2%), and 1 in the penile urethra (5.6%). Type of surgery included 6 (33%) buccal mucosa onlay grafts (5 dorsal, 1 ventral), augmented anastomotic repair, (n=2, 11.1%), and excision and primary anastomosis (n=10, 55.6%). Mean days from surgery to first post-operative 24 hour bladder diary was 287.5 days (median 109, range, 32-1116). Maximum voided volume increased after surgery (p = 0.02). Overall, nocturnal voiding parameters improved after urethroplasty and trended towards significance primarily by increases in functional bladder capacity measured by the maximum voided volume (mean preop 333ml, post-op 406.6, p=0.02), number of nightly voids (mean 1.8 to 1.2, p=0.07), and the nocturnal bladder capacity index (mean 1.2 to 0.8, p=0.13) and the correlation of the degree of urgency with the voided volume (Spearman's rho mean 0.5 to 0.6, p=0.09). Urethroplasty did not improve nocturnal voiding parameters by changes in urine production as measured by changes in the 24 hour voided volume, nocturnal urine volume, the nocturnal urine production rate or the nocturnal polyuria index. CONCLUSIONS Anterior urethral reconstruction improves nocturnal voiding parameters by improving functional bladder capacity. The maximum voided volume, actual night time voids, nocturnal bladder capacity index and Spearman's rho most significantly improved. This is the first study evaluating changes in nocturnal voiding function after urethroplasty. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e470-e471 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Rajveer Purohit More articles by this author Jyoti D. Chouhan More articles by this author frank copeli More articles by this author Dennis Robins More articles by this author Andrew Tam More articles by this author Jeffrey P Weiss More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Nocturnal Enuresis in Children and Adolescent with Sickle cell Anemia

Children with sickle cell anemia (SCA) have a tendency to have nocturnal enuresis (NE) more than normal children with males being more affected than females. Mechanisms of NE that operate in normal children probably do so in children with SCA. Postulated causes of nocturnal enuresis in individuals with SCA include hyposthenuria causing nocturnal polyuria, reduced bladder capacity or nocturnal bladder overactivity, sleep disordered breathing and an increased arousal thresholds. The variation in the reported prevalence rate of NE in SCA is probably due to differences in definition criteria and methodology. This review will discuss the prevalence rate and postulated causes of NE in children with SCA.

Combination treatment of nocturnal enuresis with desmopressin and indomethacin.

We investigated the effect of combining indomethacin and desmopressin in treating children with monosymptomatic nocturnal enuresis (MNE) and desmopressin-resistant nocturnal polyuria. Twenty-three children with MNE, nocturnal polyuria, and partial or no response to desmopressin were recruited from incontinence clinics of our tertiary referral center. We used a randomized single-arm crossover placebo-controlled study design consisting of two 3-week treatment periods with a combination of desmopressin (0.4mg) and indomethacin (50mg) or desmopressin and placebo at bedtime. Home recordings at baseline and for the final 2weeks of each treatment period were performed and included nocturnal urine output measurements. The number of dry nights achieved and reduction in the nocturnal urine output were the main effect parameters. Student's t test and Pearson's correlation coefficient were used for statistical analysis. The addition of indomethacin to desmopressin significantly reduced nocturnal urine output (from 324 ± 14ml to 258 ± 13ml, p < 0.001). This did not lead to more dry nights in all children, and we found no statistically significant reduction in enuresis frequency (from 68% ± 0.1 to 56% ± 0.1, p = 0.24). Addition of indomethacin to desmopressin can further reduce nocturnal urine output in children with MNE and desmopressin-resistant nocturnal polyuria. The combination treatment does not, however, improve outcome in terms of frequency of nights with enuresis. The dissociation of antidiuretic and antienuretic effect may reflect nocturnal bladder reservoir dysfunction in children who present with normal daytime bladder function.

The impact of nocturnal polyuria in older people with nocturnal LUTS.

Bladder dysfunctions often express the presence of lower urinary tract symptoms (LUTS) and are common in older people. The aim of this study was to analyze the micturition, incontinence and residual in older subjects, evaluating the role of nocturnal polyuria. Eighty-six patients aged 65 or older with invalidating LUTS were hospitalized for 24 hours. The maximum bladder capacity, mean micturition volume, post voiding residual and incontinence volume were recorded and analyzed day-time and night-time. Three groups were defined, i.e. nocturia, nocturnal incontinence and nocturnal polyuria (NP), and patients with or without NP were analyzed. With a majority of female patients 85% and a mean age of 74.3±5.96 years, a high incidence of nocturia (76%) was observed. NP was associated with nocturia in 56 patients (86%). In the three groups, the maximum bladder capacity and mean micturition volume were statistically higher during the night. Patients with nocturia or nocturnal incontinence associated to NP presented with a higher nocturnal maximum bladder capacity and mean micturition volume. A higher nocturnal post-void residual (PVR) was observed in patients with Nocturnal Incontinence associated with NP (P=0.03). Patients without NP presented significantly higher diurnal results. Nocturnal LUTS in older people is the result of a high nocturnal urine production related to NP with a higher nocturnal bladder capacity. The analyses of micturition, incontinence and PVR, and the accurate evaluation of the presence or absence of NP seems to be the key point for a better therapeutic choice in patients suffering by Nocturnal LUTS.

Changes in Nocturnal Bladder Diary Parameters in Men after Urethroplasty for Anterior Urethral Strictures

Changes in Nocturnal Bladder Diary Parameters in Men after Urethroplasty for Anterior Urethral Strictures

Alarme noturno e enurese: uma revisão baseada na evidência

Introduction: Nocturnal enuresis is a common problem, affecting about 15% of children between the ages of five and six years. Different treatments have been studied in order to diminish the potentially stigmatizing impact of NE, both for the child and the family. These include nocturnal alarms and behavior modification affecting sleep. Aim: The aim of this review was to assess the evidence for the effectiveness of nocturnal alarms in the treatment of nocturnal enuresis. Methods: A bibliographic review of international databases was conducted, using the MeSH terms ‘Nocturnal enuresis’ AND ‘Clinical alarms’. We also consulted the Index RMP database using the search terms Enurese noturna and Alarme. We selected meta-analyses, systematic reviews, randomized controlled trials, observational studies, and clinical guidelines written in Portuguese and English that were published between January 2005 and January 2015. The Oxford Centre for Evidence-Based Medicine criteria were used to establish the Level of Evidence (LE). Results: From a total of 52 articles found, nine met the inclusion criteria. These included three systematic reviews, three clinical trials, and three guidelines. Most studies found that NA is more beneficial than other non-pharmacologic options. When compared to desmopressin, the use of NA has shown equivalent effectiveness. Its use is associated with less risk of relapse and a better response when NE occurs due to diminished nocturnal bladder capacity. However, beneficial results take longer to appear with NA, parental collaboration is needed, and there is a risk of decreased adherence to this treatment. Clinical guidelines agree with the results of published trials. Discussion: Given the potential benefits of nocturnal alarms in the treatment of nocturnal enuresis (Level of Evidence 1, Strength of Recommendation A), the family doctor should consider this treatment for NE resistant to initial measures, thus avoiding the need for pharmacologic intervention or premature referral.