Development of a Novel Prediction Tool for Response to First-Line Treatments of Monosymptomatic Nocturnal Enuresis: A Randomized, Controlled, International, Multicenter Study (DRYCHILD).

PURPOSE: Nocturnal urine volume and bladder reservoir function are key pathogenic factors behind monosymptomatic nocturnal enuresis (MNE). We investigated the predictive value of these together with other demographic and clinical variables for response to first-line treatments in children with MNE. MATERIALS AND METHODS: A randomized, controlled, international, multicenter study was conducted in 324 treatment-naïve children (6-14 years old) with primary MNE. The children were randomized to treatment with or without prior consideration of voiding diaries. In the group where treatment choice was based on voiding diaries, children with nocturnal polyuria and normal maximum voided volume (MVV) received desmopressin (dDAVP) treatment, and children with reduced MVV and no nocturnal polyuria received an enuresis alarm. In the other group, treatment with dDAVP or alarm was randomly allocated. RESULTS: A total of 281 children (72% males) were qualified for statistical analysis. The change of responding to treatment was 21% higher in children where treatment was individualized compared to children where treatment was randomly selected (risk ratio = 1.21 [1.02-1.45], P = .032). In children with reduced MVV and no nocturnal polyuria (35% of all children), individualized treatment was associated with a 46% improvement in response compared to random treatment selection (risk ratio = 1.46 [1.14-1.87], P = .003). Furthermore, we developed a clinically relevant prediction model for response to dDAVP treatment (receiver operating characteristic curve 0.85). CONCLUSIONS: The present study demonstrates that treatment selection based on voiding diaries improves response to first-line treatment, particularly in specific subtypes. Information from voiding diaries together with clinical and demographic information provides the basis for predicting response. CLINICAL TRIAL REGISTRATION NO.: NCT03389412.

Introductory editorial: Lifelong LUTS, a matter of transition?

INTRODUCTION: The EPIC study has highlighted the prominence of nocturia as a crucial symptom of overactive bladder (OAB), intertwining OAB and nocturia with bladder, kidney, and brain functions. METHODS: Expert opinion, review. RESULTS: To truly comprehend lower urinary tract symptoms (LUTS), we must delve into the interactions among these three systems, alongside their circadian rhythms. CONCLUSION: The perception of LUTS is a result of the intricate interplay between bladder, brain, and kidney function, which may evolve across a lifetime due to the (dys)functionality of these organs.

The pooled analysis evaluates the therapeutic efficacy of desmopressin combined with anticholinergic drugs in the treatment of pediatric nocturnal enuresis.

OBJECTIVE: This pooled analysis aims to demonstrate the clinical efficacy and safety of combined desmopressin and anticholinergic therapy in the treatment of pediatric nocturnal enuresis (NE). METHODS: A systematic search was conducted through PubMed, MEDLINE, EMBASE, ResearchGate, and Cochrane Library to identify all randomized controlled trials (RCTs) comparing monotherapy with desmopressin versus combined therapy with desmopressin and anticholinergic agents for the treatment of NE. Data analysis was performed using RevMan version 5.4.1. RESULTS: This study included 8 RCTs involving a total of 659 patients. The frequencies of complete response (CR), partial response (PR), and nonresponse (NR) were computed for both short-term treatment (1 month) and long-term treatment (3 months). Additionally, alterations in the mean number of NE episodes, adverse events, and relapse were assessed. Our analysis indicates that, in comparison to the monotherapy group, the combination therapy group plays a pivotal role in augmenting the CR odds and diminishing the NR ratios in both short-term and long-term treatments (1 month CR ratio [risk ratio (RR): 1.84; 95% confidence interval (CI): 1.22-2.76; p = 0.003, I2 = 72%]; 3 months CR ratio [RR: 1.48; 95% CI: 1.25-1.76; p < 0.00001, I2 = 0%]; 1 month NR ratio [RR: 0.67; 95% CI: 0.55-0.82; p = 0.0001, I2 = 0%]; 3 months CR ratio [RR: 0.37; 95% CI: 0.19-0.73; p = 0.004, I2 = 0%]). Furthermore, in both short-term and long-term treatment, the combined therapy group exhibits a greater magnitude of change in the average number of NE episodes compared to patients receiving monotherapy (1 month, mean difference [MD] = -2.97; 95% CI: -4.23 to -1.71, p < 0.0001; 3 months, MD = -4.30; 95% CI: -7.18 to -1.43, p = 0.003). Moreover, the combination therapy group exhibits a significant reduction in the recurrence rate (RR: 0.36; 95% CI: 0.15-0.86; p = 0.02). There is no significant difference in the incidence of adverse events between the two groups (RR: 1.16; 95% CI: 0.58-2.31; p = 0.67). CONCLUSION: Combining desmopressin with anticholinergic medications is more effective for NE than desmopressin alone, with lower recurrence and minimal adverse effects.

NITES, a nocturnal bladder score to aid diagnosis during the transition to older age care.

BACKGROUND: As adults transition to older age, bothersome nocturnal lower urinary tract symptoms (LUTS) become common. There is need for a reliable assessment metric to detect and measure specific symptoms. OBJECTIVE: To subject the nocturnal LUTS score for older individuals, Nocturia, Incontinence, Toileting and Enuresis Symptom Score (NITES), to psychometric analysis. MATERIAL AND METHODS: Factor analysis of the metric was conducted with completed questionnaires from 151 older individuals who were either admitted to a tertiary hospital or attending an outpatient continence clinic. Test re-test reliability involved 18 older community dwelling individuals attending a Geriatrician clinic completing the metric at two timepoints separated by at least 1 week. Intra-class correlation coefficients were determined for reliability of each factor and item. RESULTS: The NITES metric was completed by 98 hospitalized older individuals and 53 attending a continence clinic (mean age 83.2 years [SD 7.0]). Factor analysis demonstrated that one item had a floor effect and two items had poor endorsement. After test re-test reliability analysis, a further three items were removed: one due to poor correlation between timepoints and two demonstrating inadequate internal consistency. The final NITES metric is comprised of three factors: Sleep 4-items, Incontinence 4-items, and Personal Bother 2-items. A 4-item short form for symptom screening was extracted from the longer measure. CONCLUSION: The final NITES metric is a 10-item questionnaire with an embedded 4-item short symptom screen. It has utility utilized to detect nocturnal bladder symptoms in both community dwelling and hospitalized older adults.

Discontinuing absorbent pants in children with bedwetting: a randomized controlled trial.

The objective of this study is to examine the effect of discontinuing wearing protective garments (absorbent pyjama pants - APP) in children with severe childhood nocturnal enuresis (NE). The study employs a multicenter, parallel, randomized controlled trial. Following a 4-week run-in period, participants were randomly allocated in a 2:1 group allocation to discontinue or continue using APP. The research was conducted across seven European pediatric incontinence centers. The study included treatment-naïve children aged 4-8 years with severe (7/7 wet nights per week) mono-symptomatic NE, who had used nighttime protection for at least 6 months prior to the study. The study consisted of a 4-week run-in period (± 7 days), where all children slept wearing APP (DryNites®). At week 4 (± 7 days), if meeting randomization criteria (7/7 wet nights during the last week of run-in), participants were randomized to continue to sleep in APP or to discontinue their use for a further 4 weeks, with the option of another 4 weeks in the extension period. The primary outcome was the difference between groups of wet nights during the last week of intervention. Quality of life (QoL) and sleep were secondary endpoints. In total, 105 children (43 girls and 62 boys, mean age 5.6 years [SD 1.13]) were randomized (no-pants group n = 70, pants group n = 35). Fifteen children (21%) in the no-pants group discontinued early due to stress related to the intervention. Children in the no-pants group experienced fewer wet nights compared to the pants group during the last week (difference 2.3 nights, 95% CI 1.54-3.08; p < 0.0001). In the no-pants group, 20% responded to the intervention, of whom 13% had a full response. Clinical improvement was detected within 2 weeks. Sleep and QoL were reported as negatively affected by APP discontinuation in the extension period but not in the core period.    Conclusion: A ~ 10% complete resolution rate was associated with discontinuing APP. While statistically significant, the clinical relevance is debatable, and the intervention should be tried only if the family is motivated. Response was detectable within 2 weeks. Discontinuing APP for 4-8 weeks was reported to negatively affect QoL and sleep quality. No severe side effects were seen.Trial registration: Clinicaltrials.gov Identifier: NCT04620356; date registered: September 23, 2020. Registered under the name: "Effect of Use of DryNites Absorbent Pyjama Pants on the Rate of Spontaneous Resolution of Paediatric Nocturnal Enuresis (NE)."

Autonomic nervous system dysregulation in children with monosymptomatic nocturnal enuresis.

AIM: To investigate the role of autonomic nervous system in subpopulations of children with enuresis. METHODS: We included 35 children with enuresis, divided in children with (17) and without nocturnal polyuria (18) and 43 healthy controls. For all participants hormones and neurotransmitters were measured. Patients and controls wore a sleep tracker device and children with enuresis underwent a 24 h blood pressure monitoring, nocturnal urine output measurement and uroflowmetry. RESULTS: Children with enuresis had lower than controls copeptin and aldosterone, with the latter being more prominent in patients without nocturnal polyuria. Dopamine was lower in patients without nocturnal polyuria compared with patients with nocturnal polyuria. Children without polyuria experienced episodes only during NREM sleep, whereas in children with polyuria episodes occurred in both REM and NREM sleep. Children with enuresis experienced a non-dipping phenomenon during sleep which was more prominent in the group without polyuria. CONCLUSION: In patients with nocturnal polyuria, nocturnal enuresis is associated with sympathetic hyperactivity which results in pressure polyuria and significantly lower systolic dipping during sleep. On the contrary, in children without nocturnal polyuria, it is mostly associated with bladder overactivity due to parasympathetic overstimulation as demonstrated by the NREM-related enuretic episodes and the lower aldosterone and dopamine levels.

Abnormal microstructure of corpus callosum in children with primary nocturnal enuresis: a DTI study.

Primary nocturnal enuresis (PNE) is a common childhood disorder with abnormal sleep or arousal. The corpus callosum (CC) continues to develop into adulthood and plays an important role in sleep arousal. This study aimed to evaluate the microstructure of the CC in children with PNE. Diffusion tensor imaging (DTI) indices were extracted throughout the CC and its seven subregions were compared between the children with PNE and healthy children (HC). The correlation between abnormal DTI indices of the CC and cognitive condition was also tested. Compared to HC, decreased fiber number (NF) (F = 8.492, PFDR = 0.032) and fractional anisotropy (FA) value (F = 8.442, PFDR = 0.040) were found in the posterior midbody of the CC, increased RD was found in the posterior midbody (F = 6.888, PFDR = 0.040) and isthmus (F = 7.967, PFDR = 0.040) in children with PNE. The reduction of FA value was more obvious in boys than girls with PNE. In children with PNE, there was a significant positive correlation between the NF of the posterior midbody and full IQ (r = 0.322, P = 0.025) and between the FA value and the general knowledge memory (r = 0.293, P = 0.043). This study provides imaging evidence for abnormalities in the microstructure of the CC in children with PNE, especially in male PNE, which might affect the children's cognitive performance.

Wearable-Based Integrated System for In-Home Monitoring and Analysis of Nocturnal Enuresis.

Nocturnal enuresis (NE) is involuntary bedwetting during sleep, typically appearing in young children. Despite the potential benefits of the long-term home monitoring of NE patients for research and treatment enhancement, this area remains underexplored. To address this, we propose NEcare, an in-home monitoring system that utilizes wearable devices and machine learning techniques. NEcare collects sensor data from an electrocardiogram, body impedance (BI), a three-axis accelerometer, and a three-axis gyroscope to examine bladder volume (BV), heart rate (HR), and periodic limb movements in sleep (PLMS). Additionally, it analyzes the collected NE patient data and supports NE moment estimation using heuristic rules and deep learning techniques. To demonstrate the feasibility of in-home monitoring for NE patients using our wearable system, we used our datasets from 30 in-hospital patients and 4 in-home patients. The results show that NEcare captures expected trends associated with NE occurrences, including BV increase, HR increase, and PLMS appearance. In addition, we studied the machine learning-based NE moment estimation, which could help relieve the burdens of NE patients and their families. Finally, we address the limitations and outline future research directions for the development of wearable systems for NE patients.

The effectiveness of parasacral transcutaneous electrical nerve stimulation in the treatment of monosymptomatic enuresis in children and adolescents: a systematic review.

BACKGROUND: Parasacral Transcutaneous Electrical Nerve Stimulation (PTENS) is a treatment used in enuresis refractory to first-line treatment. This review aimed to evaluate the effectiveness of PTENS in treating monosymptomatic enuresis (MNE) in children and adolescents. METHODS: The study followed the Preferred Reporting Items for Systematic (PRISMA) guidelines. The search was carried out in the following databases: MEDLINE (via PubMed), Web of Science, SCOPUS, Central Cochrane Library and Physiotherapy Evidence Database (PEDro). The selected studies were randomized clinical trials (RCTs). The "Risk of Bias tool for randomized trials" and the "Risk of Bias VISualization" were used to analyze the risk of bias. RESULTS: Of the 624 studies selected, four RCTs were eligible. Three included 146 children and adolescents aged between six and 16.3 years and used similar PTENS protocols with a frequency of 10 Hz, pulse duration of 700 µs and 20 minutes three times/week. One study enrolled 52 patients aged seven to 14 years used PTENS at home, with a pulse duration of 200 µs and 20 to 60 minutes twice/day. Risk of bias was observed in three studies due to results' randomization and measurement. Two studies showed a partial response with a reduction in wet nights, one a complete response in 27% of patients, and one showed no improvement. CONCLUSION: PTENS reduces wet nights' frequency but does not cure them, except in 27% of patients in one study. Limited RCTs and data heterogeneity are limitations.

Diurnal rhythm of urinary aquaporin-2 in children with primary monosymptomatic nocturnal enuresis.

Background/aim: Nocturnal enuresis can be frustrating for children and their families as the child ages. Our aim is to evaluate urine aquaporin 2 (AQP-2) as a noninvasive biomarker of water balance in children with primary monosymptomatic nocturnal enuresis (PMNE). Material and methods: The study included 90 children; sixty-eight children suffering from PMNE aged (9.57 ± 2.16) years and 22 healthy children with good toilet control, matched sex and age. All enuretic children were subjected to complete history taking, clinical evaluation, and bed wetting diary. Serum arginine vasopressin (AVP) and urine AQP-2 were tested in the morning (at 9-11 am) and evening (at 9-11 pm). Blood urea, creatinine, Na, glucose, urine osmolality, Ca/Cr, Alb/Cr and specific gravity were tested simultaneously. Results: Serum AVP, urine AQP-2, and urine osmolality were statistically lower in patients than controls. Patients had a significantly lower level of night serum AVP concentrations, urine AQP-2, and urine osmolality than the corresponding morning level. Urine AQP-2 was significantly correlated with urine osmolality (p < 0.05). AQP-2 had a sensitivity of 90% and a specificity of 70%. However, no statistically significant correlation was found between serum AVP and urine AQP-2. Conclusion: Primary monosymptomatic nocturnal enuresis in children could be associated with reduction of urine excretion of AQP-2 at night. Urine AQP-2 is significantly correlated with urine osmolality. Therefore, it may be a noninvasive biomarker of hydration status in children with PMNE, with good sensitivity and specificity.

The genetics of incontinence: A scoping review.

The genetic causes underlying incontinence in both children and adults have begun to be unravelled during the last decades. The aim of this scoping review is to synthesize current knowledge on the genetics of childhood and adult urinary and faecal incontinence, identify similarities between different incontinence subgroups, and identify knowledge gaps to aid future research. PRISMA-ScR was used, and 76 studies were included. Early epidemiological family and twin studies suggest high heritability of incontinence. Linkage studies provide evidence for the existence of rare genetic variants; however, these variants have not been identified. Later candidate gene association studies and recent genome-wide association studies provide the first preliminary evidence that common risk variants also play a role. The genetics of incontinence in children and adults has predominantly been studied separately, but this review identifies for the first time the endothelin system as a potential common pathophysiological pathway. Overall, these findings strengthen the hypothesis that genetic variants play a prominent role in the pathogenesis of incontinence. Future research should include hypothesis-free studies of rare and common variants in large well-characterized cohorts with incontinence. Studies should include different age groups and ethnicities and both sexes to fully reveal the genetics of incontinence.

Relationship between nocturnal enuresis and sleep in children and adolescents.

BACKGROUND: Nocturnal enuresis (NE) is a multifactorial and complex condition. One less understood factor in its pathophysiology is the enuretic inability to wake up when the bladder is full (impaired arousal). OBJECTIVE: We aimed to investigate the relationship between sleep and NE in children and adolescents. METHODS: A systematic review was performed following the PRISMA guidelines, and the electronic databases MEDLINE (via PubMed) and SCOPUS were searched until March 2022. Eligibility criteria were studies that recruited patients aged five-17 years with a diagnosis of NE according to the International Child Continence Society (ICCS), Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5), or International Classification Criteria of Sleep Disorders-Third edition (ICSD-3) who had their sleep assessed using validated questionnaires and/or polysomnography. The tool used to analyze the risk of bias in the included studies was the risk of bias in non-randomized studies of exposure. RESULTS: Of 1582 citations screened, nine were included, giving 1685 participants, 581 with NE. All studies were observational and half had a low risk of bias. Four studies evaluated sleep by questionnaires only; two used questionnaires and polysomnography; two used only polysomnography, and one used sleep logs and actigraphy. Sleep questionnaires showed that children with enuresis had more sleep problems than controls, especially parasomnias, breathing disorders, and daytime sleepiness. Among the polysomnography parameters, the sleep stage architecture and periodic limb movements during sleep had conflicting data between the two studies. LIMITATIONS: The studies evaluated sleep through heterogeneous tools. They used different questionnaires; even those considered by polysomnography did not record the same channels. CONCLUSION: It seems that enuretic children and adolescents sleep differently from those who are non-enuretic. More studies are needed to clarify the best way to assess sleep and better understand this relationship. The review protocol was registered with PROSPERO, CRD42021266338. There was no funding.

Differences in the urinary metabolome and proteome between wet and dry nights in children with monosymptomatic nocturnal enuresis and nocturnal polyuria.

BACKGROUND: Nocturnal enuresis (NE) is a common disease with multiple pathogenic mechanisms. This study aimed to compare levels of metabolites and proteins between wet and dry nights in urine samples from children with monosymptomatic NE (MNE). METHODS: Ten boys with MNE and nocturnal polyuria (age: 7.6 ± 1.3 years) collected their total nighttime urine production during a wet and a dry night. Untargeted metabolomics and proteomics were performed on the urine samples by liquid chromatography coupled with high-mass accuracy tandem mass spectrometry (LC-MS/MS). RESULTS: On wet nights, we found reduced urine osmolality (P = 0.025) and increased excretion of urinary potassium and sodium by a factor of, respectively, 2.1 (P = 0.038) and 1.9 (P = 0.19) compared with dry nights. LC-MS identified 59 metabolites and 84 proteins with significantly different levels between wet and dry nights (fold change (FC) < 0.67 or > 1.5, P < 0.05). Some compounds were validated by different methodologies. During wet nights, levels of compounds related to oxidative stress and blood pressure, including adrenalin, were increased. We found reduced levels of aquaporin-2 on wet nights. The FCs in the 59 metabolites were positively correlated to the FCs in the same metabolites identified in urine samples obtained during the evening preceding wet and dry nights. CONCLUSIONS: Oxidative stress, which in the literature has been associated with nocturia and disturbances in sleep, might be increased during wet nights in children with MNE. We further found evidence of increased sympathetic activity. The mechanisms related to having wet nights in children with MNE seem complex, and both free water and solute handling appear to be important. A higher resolution version of the Graphical abstract is available as Supplementary information.

Combination therapy (desmopressin plus oxybutynin) improves the response rate compared with desmopressin alone in patients with monosymptomatic nocturnal enuresis and nocturnal polyuria and absence of constipation predict the response to this treatment.

Combination therapy (CT) (desmopressin plus oxybutynin) has been considered for the treatment of monosymptomatic nocturnal enuresis (MNE). We designed our study with the aim to evaluate the response rate to CT compared with desmopressin alone (primary outcome) and to identify factors associated with the response to CT (secondary outcome). We prospectively enrolled children with MNE with absent/partial response after 3 months of evening treatment with 240 mcg of desmopressin. We defined the response rate to CT compared with desmopressin alone according to the standardization of terminology document of the International Children's Continence Society: no-response, < 50% reduction; partial response, 50 to 99% reduction; and complete response, 100% reduction of wet nights. Both partial response and complete response to CT were clustered for the analyses of this manuscript. The enrolled children treated with 240 mcg/evening of desmopressin had also an additional evening administration of 0.3 mg/kg oxybutynin. A follow-up was scheduled at 3 and 6 months after the beginning of CT. At 3 months, oxybutynin dose was augmented to 0.5 mg/kg in case of absent/partial response to CT. Nocturnal diuresis was measured in 5 wet nights prior the beginning of therapy with desmopressin. Nocturnal polyuria (NP) was defined as nocturnal urine production > 130% of the expected bladder capacity. All patients with constipation were treated with macrogol. We enrolled 81 children (35.8% females) with a mean age of 8.4 ± 2.3 years. Seventy-eight patients completed the follow-up. After the CT, 59/78 (75.6%) patients showed an improvement of the response with CT compared with desmopressin alone. At multivariate analysis, both NP in more than 1 night (OR = 8.5; 95% CI, 1.4-51.6; p = 0.02) and absence of constipation (OR = 7.1; 95% CI, 1.6-31.0; p = 0.009) resulted significant after Bonferroni correction. CONCLUSIONS: CT determines an improvement of response compared to therapy with desmopressin alone in 75.6% of patients. Significant predictive factors of response to CT were presence of NP and absence of constipation. WHAT IS KNOWN: • Combination therapy (CT) (desmopressin plus anticholinergic drug) has been described as a therapeutic option for patients with monosymptomatic nocturnal enuresis (MNE) not responding to desmopressin alone as first-line treatment. • Variable protocols and variable combination of drugs have been described with a response rate ranging from 44 to 76%. WHAT IS NEW: • We found that 59 patients (75.6%) treated with evening administration of 240 mcg of sublingual desmopressin plus 0.3-0.5 mg/kg of oxybutynin had an improvement of response compared to treatment with desmopressin alone. • We add evidence that presence of frequently recurring nocturnal polyuria and absence of constipation are predictors of response to CT.

The effect of screen time on the presentation and treatment of primary monosymptomatic nocturnal enuresis.

BACKGROUND: We aimed to investigate if there was any relationship between screen time (ST) and the severity of primary monosymptomatic nocturnal enuresis (PMNE) and treatment success. METHODS: This study was conducted in urology and child and adolescent phsychiatry clinic in Afyonkarahisar Health Sciences University Hospital. After diagnosis patients were seperated by the ST for exploring causation. Group 1 > 120, Group 2 < 120 (min/day). For the the treatment response, patients were grouped again. Group 3 patients were administered 120 mcg Desmopressin Melt (DeM) and were requested < 60 min ST. Patients in Group 4 were given 120 mcg DeM solely. RESULTS: The first stage of the study included 71 patients. The ages of the patients ranged from 6 to 13. Group 1 comprised 47 patients, 26 males and 21 females. Group 2 comprised 24 patients,11 males and 13 famales. Median age was 7 years in both groups. The groups were similar in respect of age and gender (p = 0.670, p = 0.449, respectively). A significant relationship was determined between ST and PMNE severity. Severe symptoms were seen at the rate of 42.6% in the Group 1, and at 16.7% in the Group 2 (p = 0.033). 44 patients completed the second stage of the study. Group 3 comprised 21 patients, 11 males and 10 females. Group 4 comprised 23 patients,11 males and 12 famales. Median age was 7 years in both groups. The groups were similar in respect of age and gender (p = 0.708, p = 0.765, respectively). Response to treatment was determined as full response in 70% (14/20) in Group 3 and in 31% (5/16) in Group 4 (p = 0.021). Failure was determined in 5% (1/21) in Group 3 and in 30% (7/23) in Group 4 (p = 0.048). Recurrence was determined at a lower rate in Group 3 where ST was restricted (7% vs. 60%, p = 0.037). CONCLUSION: High screen exposure may be a factor for PMNE aetiology. And also reducing ST to a normal range can be an easy and beneficial method for treatment of PMNE. Trial Registration ISRCTN15760867( www.isrctn.com ). Date of registration: 23/05/2022. This trial was registered retrospectively.

Evaluation of the association between asthma and non-neurogenic urinary incontinence in children; a case-control study.

BACKGROUND: Asthma is the most common chronic disease in children. Asthma can lead to sleep disorders and psychiatric issues, which are often accompanied by urinary incontinence in children. Furthermore, several studies have shown a relationship between allergic diseases and urinary incontinence. This study aims to examine the association between asthma and non-neurogenic urinary incontinence. MATERIALS AND METHODS: This case-control study included 314 children over three years old referred to Amir Kabir Hospital; 157 with asthma and 157 without asthma. After explaining each urinary disorder in accordace with the International Children's Continence Society's definitions, parents and children were asked about their presence. The disorders included monosymptomatic nocturnal enuresis(MNE), nonmonosymptomatic nocturnal enuresis (NMNE), vaginal reflux (VR), pollakiuria, infrequent voiding, giggle incontinence (GI), and overactive bladder (OAB). The analysis was performed using Stata 16. RESULTS: The average age of the children was 8.19 ± 3.15 years. Patients with asthma (p = 0.0001) and GI (p = 0.027) had a considerably lower average age than patients without these disorders. Asthma and urinary incontinence, including NMNE, Infrequent voiding, and OAB, were significantly correlated (p = 0.017, 0.013, and 0.0001, respectively). Moreover, the association between MNE and asthma was significant in males (p = 0.047). CONCLUSION: Due to the relationship between asthma and urinary incontinence, children with asthma must be evaluated for the presence of urinary disorders and, if present, receive the proper treatment in order to improve their quality of life.

Effects of short-term treatment with vibegron for refractory nocturnal enuresis.

BACKGROUND: Long-term nocturnal enuresis treatment leads to stress and lowered self-esteem for children and their parents. This study evaluated the short-term effectiveness and safety of vibegron (50 mg) for children with refractory nocturnal enuresis. METHODS: A retrospective cohort study of children with therapy-resistant enuresis was conducted using data for July to December 2019. Enuresis frequency was recorded during 30 days before and after additional vibegron administration with prior treatment. We assessed the treatment effectiveness based on enuresis frequencies between before and after treatment with vibegron 50 mg. Statistical evaluation was performed using a paired t-test. RESULTS: Among 29 children receiving vibegron, 14 (48.3%) exhibited a partial or complete response to the drug. Enuresis frequencies (mean ± standard deviation [SD]) were, respectively, 15.8 ± 9.2 and 9.5 ± 9.6 before and after treatment with vibegron during the observed 30 days. A statistically significant reduction in enuresis frequency was found (p < 0.001). Moreover, maximum mean±SD morning urine of 200 ± 62.9 mL before treatment with vibegron changed to 232 ± 76.6 mL after treatment. A significant increase in voiding volume in the early morning was found (p < 0.05). No drug-related severe adverse event was found. CONCLUSION: Short-term treatment with vibegron is safe and effective for children with refractory enuresis.

Comparison of the characteristics and factors influencing hospital visits among children with nocturnal enuresis in Japan: The Hirakata-Urayasu population-based cohort study.

OBJECTIVES: The aim of this study was to compare the demographic characteristics of school-aged children with nocturnal enuresis and factors influencing hospital visits between two regions in Japan. METHODS: A cross-sectional survey was conducted in Hirakata City, Osaka Prefecture, and Urayasu City, Chiba Prefecture. An anonymous online questionnaire was administered to all public elementary and junior high school students (aged 6-16 years) or their guardians. Questions included age, gender, perinatal history, frequency of nocturnal enuresis, frequency of bowel movements, comorbidities, and hospital visits for nocturnal enuresis. RESULTS: The survey response rates were 15.4% in Hirakata City and 37.0% in Urayasu City. In total, 426 children with nocturnal enuresis in Hirakata City and 270 in Urayasu City were included in the final analysis. In both cities, the boy-girl ratio was approximately 2:1, and the prevalence of nocturnal enuresis gradually decreased with age. Multivariate analysis revealed that children aged ≥11 years had a significantly higher proportion of hospital visits (OR, 2.61; 95% CI: 1.49-4.56; p = 0.001; OR, 2.72; 95% CI: 1.12-6.64; p = 0.027, respectively). However, the frequency of nocturnal enuresis did not affect hospital visits. CONCLUSIONS: The findings of this study suggest that parents with school-aged children have low awareness that nocturnal enuresis is a health problem and therefore subject to medical consultation. Although the proportion of hospital visits increases for children aged ≥11 years, children and families suffering from nocturnal enuresis should be encouraged to see a doctor instead of adopting a "wait and see attitude," even at a young age.

Correlation between serum copeptin and urinary aquaporin-2 levels in children with primary monosymptomatic nocturnal enuresis.

OBJECTIVES: To determine the utility of serum copeptin and urinary aquaporin-2 (AQP2) levels in diagnosing primary monosymptomatic nocturnal enuresis (PMNE) in children. METHODS: This study comprised 58 children (30 males and 28 females), aged 9.7 (±2.9) years with PMNE enuresis. Another 29 children (16 males and 13 females) aged 10.2 (±3.3) without nocturnal enuresis (NE) were recruited as a control group. History taking, clinical examination, and assessment of serum copeptin (blood) and AQP-2 levels (urine) were performed in all participants. RESULTS: Serum levels of copeptin, potassium and urinary AQP-2, and urine creatinine levels were lower in the PMNE group compared to the control group (p < 0.001 for all). No significant differences in body mass index, urine specific gravity, serum sodium, serum creatinine, or estimated glomerular filtration rate were observed between groups. This study evaluated both serum copeptin and AQP-2 levels in healthy and enuretic children. CONCLUSIONS: In this study, serum levels of copeptin (blood) and AQP2 (urine) were significantly lower in enuretic patients compared to healthy controls. Further, the measurement of urinary AQP-2 levels is more practical than serum copeptin levels due to lower invasiveness.

The Safety and Efficacy of Fluoxetine for the Treatment of Refractory Primary Monosymptomatic Nocturnal Enuresis in Children: A Randomized Placebo-Controlled Trial.

PURPOSE: We investigated the efficacy and safety of fluoxetine, a selective serotonin reuptake inhibitor, for treating refractory primary monosymptomatic nocturnal enuresis in children. MATERIALS AND METHODS: Children 8-18 years old with severe primary monosymptomatic nocturnal enuresis unresponsive to alarm therapy, desmopressin, and anticholinergics were screened for eligibility. After excluding children with daytime urinary symptoms, constipation, underlying urological, neuropsychiatric, endocrinological, or cardiac conditions, patients were randomly and equally assigned to 10 mg fluoxetine once daily or placebo for 12 weeks. The primary outcome was treatment response according to the International Children's Continence Society terminology. Treatment-related adverse effects and nighttime arousal were secondary outcomes. RESULTS: A total of 150 children were enrolled, of whom 110 (56 in fluoxetine group and 54 in placebo group) with a mean age of 11.8 (SD 2.46) years were finally analyzed. After 4 weeks, 7.1% and 66.1% of the fluoxetine group achieved complete response and partial response (defined as 50%-99% reduction of the number of wet nights), respectively, versus 0% and 16.7% of the placebo group (P < .001). At 12 weeks, complete and partial responses were achieved in 10.7% and 21.4% of the fluoxetine group, respectively (vs 0% and 14.8% of the placebo group, P = .023). Fluoxetine-treated patients had fewer wet nights (4.7 [SD 4.2] fortnightly vs 9.7 [SD 3.5] at 4 weeks, P < .001; 5.7 [SD 4.4] vs 9.9 [SD 3.4] at 8 weeks, P < .001; 7.5 [SD 4.6] vs 9.9 [SD 3.4] at 12 weeks, P = .003). Fluoxetine was associated with improved nighttime arousal (P = .017), and minor and rapidly reversible adverse effects in 5 (8.9%) patients. CONCLUSIONS: Fluoxetine is safe treatment for refractory primary monosymptomatic nocturnal enuresis in children with good initial response that declines at 12 weeks.