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.

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.

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.

Management of treatment-resistant nocturnal enuresis.

Nocturnal enuresis is defined as intermittent urinary incontinence during sleep in children 5 years of age and older, occurring at least once a month for at least 3 months. In Japan, pediatricians who do not specialize in nocturnal enuresis have become more proactive in treating the condition since 2016, when the guidelines for treating it were revised for the first time in 12 years. For monosymptomatic nocturnal enuresis, the first step is lifestyle guidance, with a focus on the restriction of fluid intake at night; however, if lifestyle guidance does not decrease the frequency of nocturnal enuresis, aggressive treatment should be added. The first choice of aggressive treatment is oral desmopressin, an antidiuretic hormone preparation, or alarm therapy. However, there remain patients whose wet nights do not decrease with oral desmopressin or alarm therapy. In such cases, it is necessary to reconfirm the method of desmopressin administration and check for factors that may decrease the efficacy of desmopressin. If alarm therapy does not increase the number of dry nights, it is possible that the patient is fundamentally unsuitable for alarm therapy. If dry nights do not increase with oral desmopressin or alarm therapy, the next treatment strategy should be considered immediately to keep the patient motivated for treatment.

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.

Clinical efficacy of mebeverine for persistent nocturnal enuresis after orthotopic W-neobladder.

OBJECTIVES: To investigate the efficacy of mebeverine for nocturnal incontinence in male patients with an ileal orthotopic bladder substitute (OBS). PATIENTS AND METHODS: A randomised controlled trial was carried out for adult male patients who were nocturnal incontinent. Patients were allocated to receive mebeverine 200 mg or placebo once a day in the evening for 3 months. The primary outcome was to compare the continence status between groups, assessed by the urinary domain of the Bladder Cancer Index (BCI) and pad usage. The secondary outcomes were to assess the safety of mebeverine. RESULTS: There were 55 patients in the placebo group and 58 in mebeverine group who completed the follow-up. The median (interquartile range) interval between OBS surgery and starting treatment was 9 (4-13) years in the placebo group and 9 (6-13) years in the mebeverine group. The mean (SD) 3-month urinary domain score of the BCI was 70.8 (5.6) and 86.4 (14.2) in the placebo and mebeverine groups, respectively (P < 0.001). At 3 months, 54 (98.2%) and 26 (44.8%) patients required the use of a night-time pad in the placebo and mebeverine groups, respectively. Mebeverine reduced the risk of pad use by 53.4% (95% confidence interval 40.1-66.6; P < 0.001). Constipation occurred in one (2.1%) and three (5.8%) patients in the placebo and mebeverine groups, respectively; abdominal distention occurred in two (3.8%) of the patients in the mebeverine group (P = 0.25). CONCLUSION: Mebeverine decreases night-time pad use and improves the quality of life in male patients with an ileal OBS and is associated with minimal adverse events.

Association between winter season and desmopressin treatment efficiency in children with monosymptomatic nocturnal enuresis: a pilot study.

OBJECTIVES: The purpose of our study was to assess the association between the winter season and desmopressin treatment failure in South Chinese children with monosymptomatic nocturnal enuresis (MNE). MATERIALS AND METHODS: A retrospective study was conducted to analyze the clinical data of children with monosymptomatic nocturnal enuresis who have visited our urology clinic from January to December 2019. All patients received desmopressin treatment. Final treatment outcomes were categorized as successful (complete response) or failed (absent and partial response). The relationship between winter season and treatment response to desmopressin was evaluated. Additionally, associated risk factors were investigated with both univariate and multivariate regression analysis. RESULTS: In total, 393 patients diagnosed with MNE were included in the present study. There were no statistically significant differences in pretreatment variables at first visit between patients who visited the clinic in winter and those who did so in other seasons. However, the treatment failure rate of MNE in the winter season was higher than that of other seasons (77.50% vs. 52.74%). Multivariate logistic regression analysis demonstrated that the severity of symptoms and an initial clinic visit in the winter season were significantly related to desmopressin treatment failure in MNE patients. CONCLUSION: Winter season and severity of symptoms are two risk factors associated with desmopressin treatment failure in MNE patients.

Changes in prescribing trends and initial pharmacotherapy of children with nocturnal enuresis in Japan: a large-scale medical claims database analysis.

PURPOSE: We analyzed the annual trends in and initial choice of pharmacotherapy for children with nocturnal enuresis (NE) using a large-scale medical claims database in Japan. METHODS: A retrospective descriptive study performed using data from the Japan Medical Data Center between January 2005 and March 2019 involving 23,814 registrants under 16 years of age. In the first cohort of children with NE, we analyzed the comorbidities and associated annual pharmacotherapy prescribing trends. In the second cohort of only newly diagnosed cases, we analyzed the first prescribed age and initial choice of pharmacotherapy. RESULTS: A total of 3494 children with NE were identified (mean age, 5.1 ± 3.6 years; male, 66.0%). An incremental increase in the proportion of children administered NE medications was observed. The proportion of children treated with desmopressin significantly increased, whereas the prescription of tricyclic antidepressants significantly decreased and that of anticholinergics did not significantly change. Among the newly diagnosed children, 1897 were treated with approximately 90% of the prescribed monotherapy. Sublingual desmopressin monotherapy accounts for more than half of the initial pharmacotherapy from 2016 onward. Regardless of the drug class, pharmacological therapy was commonly initiated at the age of 8.3 ± 2.1 years. CONCLUSIONS: In Japan, the proportion of children treated with pharmacotherapy has been increasing. Furthermore, since the introduction of desmopressin sublingual formulations in 2012, a paradigm shift has occurred and this form of medication is now the most commonly prescribed, both from the annual perspective and as an initial choice among the newly diagnosed.

Does desmopressin withdrawal strategy affect relapse rates in monosymptomatic enuresis treatment?

Desmopressin plays a major role in the treatment of monosymptomatic enuresis but has the drawback of a high relapse rate after medical treatment. This study investigated the effect of the type of treatment termination on relapse in a large population of patients. A total of 1013 patients who were admitted with bedwetting to our paediatric urology clinic between October 2016 and April 2018 were evaluated retrospectively. Four hundred forty-seven monosymptomatic enuresis patients were treated with 120 µg/day oral desmopressin lyophilisate for 3 months, after which the treatment was terminated in one of two ways: immediate cessation of desmopressin (group 1; N = 209) and structured withdrawal (group 2; N = 238). In the structured withdrawal group, the patients continued to take desmopressin every other day for 15 days. All the patients were followed up 1 month after the drug was withdrawn, and the relapse rates were recorded. One month after cessation of treatment with oral desmopressin lyophilisate, the relapse rate in group 1 was 42.5% (89/209), and that in group 2 was 41.1% (98/238) (p > 0.05).Conclusion: This study, with the highest number of patients among reports in the literature, revealed that the methods used to terminate desmopressin treatment are not significantly different in monosymptomatic enuresis management. What is Known: • It is still unclear how to end the treatment in patients who are started desmopressin because of the complaint of monosymptomatic nocturnal enuresis. • Although there are papers in the literature suggesting that the drug should be discontinued gradually or by reducing the dose, there are also authors stating the opposite. What is New: • This study including vast amount of patients managed with desmopressin reveals that withdrawal strategy has no impact on relapse.

Low compliance contribute to insufficient Desmopressin response of primary monosymptomatic nocturnal enuresis and the role of voiding school.

AIMS: To evaluate the impact of compliance on the therapeutic effects of Desmopressin, as well as the importance of establishing the voiding school for low-compliance children in primary monosymptomatic enuresis treatment. METHODS: Eighty-nine patients with primary monosymptomatic enuresis treated with Desmopressin were observed during the 2017-2020 at University Children's Hospital Belgrade, Serbia. The average patients age was 7.7 ± 2.4 years; 65 (73%) were boys and 24 (27%) % were girls. After the 3 months of Desmopressin treatment, the effect of therapy was evaluated according to the compliance. After the treatment, low-compliance patients and their parents were suggested to visit a voiding school. RESULTS: A significant decrease in the median enuresis frequency was noticed during the Desmopressin treatment (25.0 (20.0-26.0) vs 10.0 (2.0-17.0) per month, before vs after treatment, respectively) (p < 0.001). Patients with low compliance had a poorer response to Desmopressin (p < 0.001). An median enuresis reduction in the good compliance group was 92.3% (86.7 -95%), while in the low compliance group was 28.6% (16.7-43.3%). After attending voiding school, there was a significant increase in compliance (p < 0.001), associated with an median percent decrease in enuresis of 84.0% (75.0-95.5%) (p < 0.001). CONCLUSION: Compliance considerably influences the beneficial effects of Desmopressin. Patients with poor therapeutic effects should be evaluated for compliance and introduced to voiding school.

Non-dipping phenomenon effects in monosymptomatic nocturnal enuresis treatment?

BACKGROUND: Monosymptomatic enuresis nocturna patients are shown to have disrupted blood-pressure regulation accompanying polyuria. In our study, we aimed to research the desmopressin response of enuresis patients with blood-pressure regulation problems. METHODS: The study included 175 patients, aged from 6-15 years, with a diagnosis of monosymptomatic enuresis nocturna. Before treatment, 24 h ambulatory blood-pressure monitoring (ABPM) was used to identify 52 non-dipper patients and 73 patients with normal results. The responses to desmopressin treatment and clinical and demographic characteristics affecting response were compared. RESULTS: The response to desmopressin treatment was found to be significantly low in the patients who were non-dippers on 24 h ABPM before treatment compared to those with normal ABPM results (P < 0.05). Similarly, the waking problems in the non-dipper group were found to be high by a significant degree (P < 0.05). In the non-dipper group, the systolic non-dipping rate was higher. CONCLUSIONS: Before desmopressin use, assessment of patients with a 24 h ABPM may be beneficial to select the method to be used for treatment.

Evaluating nocturnal polyuria in Japanese children with nocturnal enuresis.

BACKGROUND: The purpose of this study was to assess whether enuretic Japanese patients with nocturnal polyuria (NP) who met Hoashi's criteria (6-9 years: ≥200 mL; 10 years and older: ≥250 mL) met the International Children's Continence Society (ICCS; expected bladder capacity × 130%) and Rittig's criteria for nocturnal polyuria (>[age+9] × 20 mL). We also compared the effectiveness of 1-desamino-8-d-arginine vasopressin (DDAVP) with the three criteria. METHODS: Fifty-four patients who had NP with normal bladder capacity were enrolled: 36 boys (67%); median age, 8 (interquartile range: 7-9). We compared the diagnostic differences between the Hoashi's criteria and international standards (ICCS and Rittig's) for NP and the short-term effects of DDAVP. The patients received DDAVP for 8 weeks; we evaluated the association between each evaluation method and the effects of therapy. RESULTS: Only 17% of the patients met both Hoashi's and ICCS criteria, whereas 26% met both Hoashi's and Rittig's criteria. The therapeutic effect of DDAVP did not differ significantly between these two groups: there was an effective rate of 73% (Hoashi's criteria) versus 50% (ICCS criteria), P = 0.19, and an effective rate of 71% (Hoashi's criteria) versus 62% (Rittig's criteria), P = 0.84. CONCLUSIONS: Hoashi's criteria are widely used but, according to both the ICCS and Rittig's criteria, approximately 80% of the patients did not fulfill the definition of NP. However, 8 weeks after the DDAVP treatment began, no significant difference was observed in the therapeutic effect of DDAVP according to each set of criteria. The definition of NP should account for the physical disparities between Japanese people and Westerners.

Desmopressin response in nocturnal enuresis without nocturnal polyuria in Japanese children.

OBJECTIVES: To evaluate whether the efficacy of desmopressin differs between patients with and without nocturnal polyuria. METHODS: A total of 65 treatment-naïve children with monosymptomatic nocturnal enuresis were enrolled (45 boys; median age 8.9 years). Patients received desmopressin as their first-line treatment. Four different standards were used (Akashi and Hoashi >0.9 mL/kg/sleeping hour; Hamano >[age + 2] × 25 × 130% mL; the International Children's Continence Society >[age + 1] × 30 × 130% mL; and Rittig >[age + 9] × 20 mL) to assess nocturnal polyuria. The effectiveness of desmopressin was compared between patients with and without nocturnal polyuria according to each standard. A response was defined as a reduction in wet nights of >50%. RESULTS: The desmopressin treatment efficacy rate was 54% for polyuria and 67% for non-polyuria patients (P = 0.20), 45% for polyuria and 68% for non-polyuria patients (P = 0.08), 54% for polyuria and 59% for non-polyuria patients (P = 0.80), and 52% for polyuria and 61% for non-polyuria patients (P = 0.61), for the Akashi and Hoashi's, Hamano's, International Children's Continence Society and Rittig's standards, respectively. CONCLUSIONS: No difference was observed in the short-term clinical efficacy of desmopressin regardless of the presence of nocturnal polyuria. Thus, this might be a feasible treatment option for patients with nocturnal enuresis without nocturnal polyuria.

A comparison of the efficacy and tolerability of treating primary nocturnal enuresis with Solifenacin Plus Desmopressin, Tolterodine Plus Desmopressin, and Desmopressin alone: a randomized controlled clinical trial.

INTRODUCTION: Nocturnal enuresis (enuresis) is one of the most common developmental problems of childhood, which has often a familial basis, causes mental and psychological damage to the child and disrupts family solace. OBJECTIVES: In this study, we compared therapeutic efficacy and tolerability of treating primary nocturnal enuresis (PNE) with solifenacin plus desmopressin, tolterodine plus desmopressin, and desmopressin alone. Because we don't have enough information about this comparison especially about solifenacin plus desmopressin. PATIENTS AND METHODS: This clinical trial study was performed on 62 patients with enuresis aged 5-15 years who referred to the urology clinic of Imam Khomeini Hospital in Ahwaz in 2017-2018. Patients were randomly assigned to one of the three different therapeutic protocols and any participants were given a specific code. After that, we compared the therapeutic response and the level of satisfaction of each therapeutic group in different months. Data were analyzed using SPSS 22 software and descriptive and analytical statistics. RESULTS: The mean age of patients was 8.70±66 years. In the therapeutic group with desmopressin and solifenacin, 19 of 20 patients (95%) achieved complete remission (1) after a 3-month treatment in comparison with monotherapy group in which 14 of 22 patients (63.63%) achieved complete remission; and in the combination therapy group of desmopressin and tolterodine, in the study and the evaluation of the consequences of 3-month treatment of this group, it was found that 17 of 20 patients (85%) had complete remission. Overall, the therapeutic response in combination therapy groups of desmopressin plus anticholinergic was higher than the monotherapy group of desmopressin alone. CONCLUSION: Our results demonstrate that the combination of desmopressin and an anticholinergic agent is highly effective in treatment of children with PMNE. Although desmopressin has long been a first - line treatment for PMNE, desmopressin monotherapy often fails to achieve a successful response in patients with PMNE.

Alarm interventions for nocturnal enuresis in children.

BACKGROUND: Enuresis (bedwetting) affects up to 20% of five-year-olds and can have considerable social, emotional and psychological effects. Treatments include alarms (activated by urination), behavioural interventions and drugs. OBJECTIVES: To assess the effects of enuresis alarms for treating enuresis in children. SEARCH METHODS: We searched the Cochrane Incontinence Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, ClinicalTrials.gov, WHO ICTRP, and handsearching of journals and conference proceedings (searched 25 June 2018), and reference lists of relevant articles. SELECTION CRITERIA: We included randomised or quasi-randomised trials of enuresis alarms or alarms combined with another intervention for treating nocturnal enuresis in children between 5 and 16 years old. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed risk of bias and extracted data. MAIN RESULTS: We included 74 trials (5983 children). At treatment completion, alarms may reduce the number of wet nights a week compared to control or no treatment (mean difference (MD) -2.68, 95% confidence interval (CI) -4.59 to -0.78; 4 trials, 127 children; low-quality evidence). Low-quality evidence suggests more children may achieve complete response (14 consecutive dry nights) with alarms compared to control or no treatment (RR 7.23, 95% CI 1.40 to 37.33; 18 trials, 827 children) and that more children may remain dry post-treatment (RR 9.67, 95% CI 4.74 to 19.76; 10 trials, 366 children; low-quality evidence). At treatment completion, we are uncertain whether there is any difference between alarms and placebo drugs in the number of wet nights a week (MD -0.96, 95% CI -2.32 to 0.41; 1 trial, 47 children; very low-quality evidence). Alarms may result in more children achieving complete response than with placebo drugs (RR 1.59, 95% CI 1.16 to 2.17; 2 trials, 181 children; low-quality evidence). No trials comparing alarms to placebo reported the number of children remaining dry post-treatment. Compared with control alarms, code-word alarms probably slightly increase the number of children achieving complete response at treatment completion (RR 1.11, 95% CI 0.97 to 1.27; 1 trial, 353 children; moderate-quality evidence) but there is probably little to no difference in the number of children remaining dry post-treatment (RR 0.91, 95% CI 0.79 to 1.05; moderate-quality evidence). Very low-quality evidence means we are uncertain if there are any differences in effectiveness between the other different types of alarm. At treatment completion, alarms may reduce the number of wet nights a week compared with behavioural interventions (waking, bladder training, dry-bed training, and star chart plus rewards) (MD -0.81, 95% CI -2.01 to 0.38; low-quality evidence) and may increase the number of children achieving complete response (RR 1.77, 95% CI 0.98 to 3.19; low-quality evidence) and may slightly increase the number of children remaining dry post-treatment (RR 1.39, 95% CI 0.81 to 2.41; low-quality evidence). The evidence relating to alarms compared with desmopressin in the number of wet nights a week (MD -0.64, 95% CI -1.77 to 0.49; 4 trials, 285 children) and the number of children achieving complete response at treatment completion (RR 1.12, 95% CI 0.93 to 1.36; 12 trials, 1168 children) is low-quality, spanning possible harms and possible benefits. Alarms probably slightly increase the number of children remaining dry post-treatment compared with desmopressin (RR 1.30, 95% CI 0.92 to 1.84; 5 trials, 565 children; moderate-quality evidence). At treatment completion, we are uncertain if there is any difference between alarms and tricyclics in the number of wet nights a week, the number of children achieving complete response or the number of children remaining dry post-treatment, because the quality of evidence is very low. Due to very low-quality evidence we are uncertain about any differences in effectiveness between alarms and cognitive behavioural therapy, psychotherapy, hypnotherapy and restricted diet. Alarm plus desmopressin may reduce the number of wet nights a week compared with desmopressin monotherapy (MD -0.88, 95% CI -0.38 to -1.38; 2 trials, 156 children; low-quality evidence). Alarm plus desmopressin may increase the number of children achieving complete response (RR 1.32, 95% CI 1.08 to 1.62; 5 trials, 359 children; low-quality evidence) and the number of children remaining dry post-treatment (RR 2.33, 95% CI 1.26 to 4.29; 2 trials, 161 children; low-quality evidence) compared with desmopressin alone. Alarm plus dry-bed training may increase the number of children achieving a complete response compared to dry-bed training alone (RR 3.79, 95% CI 1.85 to 7.77; 1 trial, 80 children; low-quality evidence). It is unclear if there is any difference in the number of children remaining dry post-treatment because of the wide confidence interval (RR 0.56, 95% CI 0.15 to 2.12; low-quality evidence). Due to very low-quality evidence, we are uncertain about any differences in effectiveness between alarm plus bladder training versus bladder training alone. Of the 74 included trials, 17 reported one or more adverse events, nine reported no adverse events and 48 did not mention adverse events. Adverse events attributed to alarms included failure to wake the child, ringing without urination, waking others, causing discomfort, frightening the child and being too difficult to use. Adverse events of comparator interventions included nose bleeds, headaches and abdominal pain. There is probably a slight increase in adverse events between code-word alarm and standard alarm (RR 1.34, 95% CI 0.75 to 2.38; moderate-quality evidence), although we are uncertain because of the wide confidence interval. Alarms probably reduce the number of children experiencing adverse events compared with desmopressin (RR 0.38, 95% CI 0.20 to 0.71; 5 trials, 565 children; moderate-quality evidence). Very low-quality evidence means we cannot be certain whether the adverse event rate for alarms is lower than for other treatments. AUTHORS' CONCLUSIONS: Alarm therapy may be more effective than no treatment in reducing enuresis in children. We are uncertain if alarm therapy is more effective than desmopressin but there is probably a lower risk of adverse events with alarms than with desmopressin. Despite the large number of trials included in this review, further adequately-powered trials with robust randomisation are still needed to determine the full effect of alarm therapy.

High daily salt intake had a negative impact on how well nocturnal enuresis treatment worked on children aged 7-10 years.

AIM: We investigated whether the daily salt intake of children with nocturnal enuresis influenced their response to 1-desamino-8-D-arginine vasopressin therapy. METHODS: This study comprised 129 children (67.4% boys) with a median age of 9.2 years (range 7.2-10.4) with monosymptomatic nocturnal enuresis who were seen at Kansai Medical University Hospital, Osaka, Japan, from 2013 to 2017. Urinary sodium concentrations were determined using a spot urine test, and the children were divided into appropriate (n = 55) and excessive salt intake (n = 74) groups based on Japanese Government guidelines. After a month of therapy, the treatment responses were compared for 39 and 50 children, respectively. RESULTS: There were no significant differences in the urea nitrogen-to-creatinine or calcium-to-creatinine ratios in the two groups. However, the excessive salt intake group showed a significantly reduced treatment response to the appropriate salt intake group. In addition, the excessive and appropriate salt intake groups showed median efficacy ratios of 8.2% and 21.8%, respectively, based on intention-to-treat analysis (P = 0.029) and 12.0% and 30.8% based on per-protocol analysis (P = 0.029). CONCLUSION: High daily salt intake significantly reduced the efficacy of ddavp therapy for nocturnal enuresis and consumption should be controlled during treatment.

Desmopressin response in nocturnal enuresis showing concentrated urine.

BACKGROUND: In Japan, the use of desmopressin (1-desamino-8-D-arginine vasopressin) is only recommended for nocturnal enuresis with unconcentrated first morning urine, which suggests a relative deficiency of antidiuretic hormone secretion during sleep. However, no such limitations have been described in a standardization document of the International Children's Continence Society. We aimed to determine whether desmopressin treatment induces any response in nocturnal enuresis with concentrated first morning urine. METHODS: Outpatients aged 6-15 years who exhibited monosymptomatic nocturnal enuresis were examined. Data were obtained from 41 treatment-naive patients (median age 9.7 years) with nocturnal enuresis, who received desmopressin as their first line of treatment. The patients were divided into two groups demonstrating unconcentrated (osmolality < 800 mOsm/L, Low-Osm group) and concentrated (osmolality ≥ 800 mOsm/L, High-Osm group) first morning urine, respectively; we compared the response to desmopressin treatment between the groups at 1 month after the administration or updosing of desmopressin; responses were defined as partial or complete according to the International Children's Continence Society standards. Mann-Whitney U-tests or Fisher's exact tests were used for analysis. RESULTS: The Low-Osm (median age 9.6 years) and High-Osm groups (median age 9.7 years) had 14 and 27 patients, respectively; the response rates to desmopressin treatment were 64.3% and 59.2%, respectively, indicating no significant differences (P = 0.99). CONCLUSION: Desmopressin treatment may be a feasible option for treating nocturnal enuresis with concentrated first morning urine.

Comparison of desmopressin, alarm, desmopressin plus alarm, and desmopressin plus anticholinergic agents in the management of paediatric monosymptomatic nocturnal enuresis: a network meta-analysis.

OBJECTIVE: To assess the efficacy of desmopressin, alarm, desmopressin plus alarm, and desmopressin plus anticholinergic agent (AA) therapy in the management of paediatric monosymptomatic nocturnal enuresis (MNE) using a network meta-analysis. MATERIALS AND METHODS: We searched the electronic databases PubMed, Cochrane Library, EMBASE and Web of Science from inception to 1 March 2018. Randomized controlled trials (RCTs) that compared desmopressin, alarm, desmopressin plus alarm, and desmopressin plus AAs were identified. The network meta-analysis was conducted with software R 3.3.2 and STATA 14.0. RESULTS: Eighteen RCTs with a total of 1 649 participants were included. The meta-analysis results showed that complete response (CR) and success rates with desmopressin plus AAs were higher than with desmopressin or alarm monotherapy. Success rates for desmopressin plus alarm therapy were higher than for alarm monotherapy. No obvious difference was observed between desmopressin plus AAs and desmopressin plus alarm therapy with regard to CR rate and success rate. The relapse rate with alarm monotherapy was much lower than with desmopressin monotherapy. Adverse events seemed to be infrequently and tolerable for all treatments. The ranking probability results were as follows: desmopressin plus AA ranked first for the outcomes of CR and success, desmopressin plus alarm therapy ranked first for mean number of wet nights per week, and alarm therapy had the lowest relapse rate. CONCLUSIONS: The network meta-analysis showed that desmopressin had similar efficacy to alarm therapy but a higher relapse rate. Desmopressin plus AA therapy was associated with better efficacy than and a similar relapse rate to desmopressin monotherapy. Desmopressin plus alarm therapy was similar to both desmopressin and alarm monotherapy in efficacy. All treatments, including desmopressin plus AAwere associated with tolerable adverse events; however, additional high-quality studies are needed for further evaluation of these treatments.

Urinary nerve growth factor can predict therapeutic efficacy in children with monosymptomatic nocturnal enuresis.

AIM: To determine the urinary levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in children with monosymptomatic nocturnal enuresis (MNE) and evaluate whether these factors can be used as biomarkers for the treatment outcome. METHODS: NGF and BDNF levels were measured and compared in 38 children (28 boys and 10 girls) with MNE and 25 children (18 boys and 7 girls) with no urinary symptoms were assessed. The mean ages in the patient and control groups were 9 and 10 years, respectively (P = .49). The patients were treated with either alarm or desmopressin therapy. RESULTS: The urinary NGF/creatinine and BDNF/creatinine ratios were significantly higher in the patient group than in the control group (P = .0003 and P = .0095, respectively). NGF and BDNF levels showed a significant positive correlation (P = .0020, r = 0.40). With respect to the degree of response, 19 patients (50%) showed complete response (CR) or partial response (PR), and 19 patients (50%) showed nonresponse (NR). The urinary NGF/creatinine and BDNF/creatinine ratios were significantly higher in the NR group than in the CR and PR groups (P = .0003 and P = .0003, respectively). CONCLUSIONS: Urinary NGF/creatinine and BDNF/creatinine ratios were significantly higher in children with MNE than in healthy controls. Urinary NGF/creatinine can be predictive factors of a poor treatment outcome in children with MNE.