deamino-arginine-vasopressin and Nocturnal-Enuresis

To conduct an overview of Cochrane systematic reviews about treatment alternatives for children and/or adolescents with enuresis.. An overview of Cochrane systematic reviews about interventions for enuresis in children/adolescents was developed between September/2021 and December/2021. The protocol was registered on PROSPERO and the search was conducted only in the Cochrane Library database without any restriction. Reviews involving any type of intervention for the treatment of enuresis in children/adolescents were included. The risk of bias was assessed using Risk of Bias in Systematic Reviews (ROBIS) and the quality of reviews was assessed using A Measurement Tool to Assess Systematic Reviews (AMSTAR-2).. Seven systematic reviews were identified. Based on the ROBIS assessment, all reviews were classified as low risk of bias. According to the AMSTAR-2 assessment, the three oldest systematic reviews were rated as critically low quality, one review was moderate quality, and the three most recent systematic reviews were rated as high quality. No difference was shown between alarm and desmopressin for a complete response to therapy after treatment (RR = 1.30; 95%CI: 0.92 to 1.84), but alarm use is related to a lower risk of adverse events (RR = 0.38; 95%CI: 0.20 to 0.71). There is a moderate certainty that the association between imipramine and oxybutynin is better than placebo to reduce the risk of children who do not achieve 14 consecutive dry nights after treatment (RR = 0.43; 95%CI: 0.23 to 0.78).. There is no difference between alarm and desmopressin for enuresis treatment. However, alarm therapy had fewer adverse events than desmopressin. Moreover, combination therapy between imipramine and oxybutynin is better than placebo.

Topics: Adolescent; Child; Deamino Arginine Vasopressin; Enuresis; Humans; Imipramine; Nocturnal Enuresis; Systematic Reviews as Topic; Urinary Incontinence

One of the common pediatric issues is monosymptomatic nocturnal enuresis (MNE). MNE is involuntarily urine-voiding in night sleep without lower urinary tract symptoms, such as daytime frequency, incontinence, or urgency. Alarm therapy and desmopressin have been used for treating MNE, but there is no clear comparison of the effectiveness of the two modalities.. This study aimed to compare the efficacy of alarm therapy and desmopressin and strategies to improve the therapy.. Study searches were conducted on PubMed, Embase, and Cochrane with a time span of 2010 to 2021. The keywords used were desmopressin, alarm therapy, pediatrics, and monosymptomatic enuresis. The study included an RCT in English, and no subjects were dropped out. Studies without a definite number of subjects were excluded.. As many as 12 studies were included in the meta-analysis, 9 of which looked for response rates, and 3 were for desmopressin-withdrawal optimization strategy. Alarm therapy was superior to desmopressin in well-motivated parents and patients (p=0.02), with a combined risk ratio of 1.10 in the low heterogeneity population (Z-score = 2.31; I. The meta-analysis shows that alarm therapy has a better response rate than desmopressin in proactive parents. However, desmopressin may be an option in the opposite subjects, and it is necessary to use structured strategies to optimize the treatment.

Topics: Child; Deamino Arginine Vasopressin; Humans; Nocturnal Enuresis; Urinary Incontinence

Nocturnal enuresis is the involuntary pass of urine during sleep beyond the age of 5 years. It is a common condition in childhood and has an impact on the child's well-being. Research into the pathophysiology of the condition in the last decades has led to a paradigm shift, and enuresis is no longer considered a psychiatric disorder but rather a maturation defect with a somatic background. An excess urine production during sleep is a common finding in children with enuresis and disturbances in the circadian rhythm of arginine-vasopressin (AVP) is found in the majority of children with nocturnal polyuria. Children with enuresis and nocturnal polyuria lack the physiologic increase in AVP levels during sleep and treatment with the AVP analogue desmopressin can restore this rhythm and lead to dry nights. The reasons for this aberrant circadian AVP rhythm are not established. Furthermore, not all children with enuresis and nocturnal polyuria can be successfully treated with desmopressin suggesting that factors beyond renal water handling can be implicated such as natriuresis, hypercalciuria, and sleep-disordered breathing. The advances in the research of the genetic background of the condition may shed further light on the enuresis pathophysiology.

Topics: Arginine; Arginine Vasopressin; Child; Child, Preschool; Circadian Rhythm; Deamino Arginine Vasopressin; Humans; Nocturnal Enuresis; Polyuria; Vasopressins

Topics for DTB review articles are selected by DTB's editorial board to provide concise overviews of medicines and other treatments to help patients get the best care. Articles include a summary of key points and a brief overview for patients. Articles may also have a series of multiple choice CME questions.

Topics: Age Factors; Antidepressive Agents, Tricyclic; Clinical Alarms; Comorbidity; Deamino Arginine Vasopressin; Humans; Muscarinic Antagonists; Nocturnal Enuresis

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.. To assess the effects of enuresis alarms for treating enuresis in children.. 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.. 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.. Two review authors independently assessed risk of bias and extracted data.. 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 slight. 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.

Topics: Absorbent Pads; Case-Control Studies; Child; Child, Preschool; Clinical Alarms; Combined Modality Therapy; Deamino Arginine Vasopressin; Humans; Nephrology; Nocturnal Enuresis; Placebos; Randomized Controlled Trials as Topic; Renal Agents; Treatment Outcome

The goal of this paper is to describe the pathophysiology of adult nocturnal enuresis and develop a generalized approach for evaluation and treatment.. Although nocturnal enuresis (NE) impacts a significant proportion of the adult population, research on this topic remains lacking. In the few existing studies, the management strategy is extrapolated from research on pediatric nocturnal enuresis. Furthermore, treatment approaches highlight the importance of identifying risk factors and contributing pathologies. The modern urologist should understand the complexity of this problem and the variety of techniques to evaluate and treat the adult patient with NE. Adult nocturnal enuresis is multifactorial and may have multiple underlying pathologies. A comprehensive workup requires an understanding of the patient's history and symptomatology and the pathophysiologic processes that can occur. Treatment should first target identifiable etiologies, although a generalized algorithm can then be utilized with behavioral and lifestyle modifications, followed by medical therapy. Future studies will provide a better framework for treating this problem.

Topics: Adult; Algorithms; Antidiuretic Agents; Behavior Therapy; Cholinergic Antagonists; Deamino Arginine Vasopressin; Humans; Nocturnal Enuresis; Risk Reduction Behavior

Enuresis is a common complaint in children, with a prevalence of around 15% at age 6 years. Evidence suggests that enuresis could affect neuropsychiatric development. The condition may represent an entire spectrum of underlying urological conditions. It is important to understand the difference between monosymptomatic and non-monosymptomatic enuresis. Primary monosymptomatic enuresis can be managed efficaciously with care in different settings, like primary care, specialist nursing, or paediatric specialists, while non-monosymptomatic enuresis requires more complex evaluation and treatment. The diagnosis, investigation, and management of the two types of enuresis are discussed in this review.

Topics: Antidiuretic Agents; Behavior Therapy; Child; Child, Preschool; Deamino Arginine Vasopressin; Humans; Nocturnal Enuresis; Physical Examination

Nocturnal enuresis causes significant psychological distress to affected children and their family and requires appropriate management. A 12-member expert committee of pediatric urologists and pediatric nephrologists in Taiwan with extensive experience in treating enuresis was established to develop consensus statements and a recommended treatment algorithm for the management of patients with nocturnal enuresis in Taiwan after careful consideration of current evidence, existing guidelines, and expert opinion as well as local practice and culture. The finalized consensus statements were reviewed by and have received endorsement from the Taiwan Urological Association and the Taiwan Pediatric Association. Patients with suspected enuresis should undergo a thorough initial assessment to fully evaluate urinary signs and symptoms and to rule out underlying causes of diurnal and nocturnal incontinence. Behavioral therapy is recommended throughout the course of management. Desmopressin in the fast-melting formulation is the recommended first-line pharmacological treatment. Combination therapy may be effective in patients who have failed first-line treatment. These consensus statements and a recommended treatment algorithm were created by the expert committee to provide practical support for clinical decision making by physicians in Taiwan.

Topics: Antidiuretic Agents; Behavior Therapy; Child; Child, Preschool; Consensus; Deamino Arginine Vasopressin; Humans; Nocturnal Enuresis; Practice Guidelines as Topic; Societies, Medical; Taiwan

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.. 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.. 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.. 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.

Topics: Antidiuretic Agents; Child; Cholinergic Antagonists; Clinical Alarms; Deamino Arginine Vasopressin; Humans; Network Meta-Analysis; Nocturnal Enuresis; Randomized Controlled Trials as Topic; Recurrence; Treatment Outcome

Nocturnal enuresis is a common problem that children may present with in a primary care setting. It is important to take a detailed history to rule out secondary causes; however, most cases are primary in nature. It is essential to demystify the problem and reassure parents by educating them that the episodes are nonvolitional and most children outgrow the problem over time. Behavioral interventions are considered first line and are most successful when the child is invested in succeeding. Interventions should be initiated with specific goals in mind. Medications are effective and should be used in conjunction with behavioral interventions.

Topics: Antidiuretic Agents; Behavior Therapy; Child; Clinical Alarms; Deamino Arginine Vasopressin; Female; Humans; Male; Nocturnal Enuresis

Nocturnal enuresis (NE) is a common health problem. Approximately 10% of 7-year-old children wet the bed regularly during sleep. Enuresis can be categorized into monosymptomatic (MEN) and nonmonosymptomatic (NMEN) forms. MEN occurs without any other symptoms of bladder dysfunction. NMEN is associated with dysfunction of the lower urinary tract with or without daytime incontinence. The rate of comorbid gastrointestinal, behavioral, and emotional disorders is elevated depending upon the subtype of NE. A careful clinical history is fundamental to the evaluation of enuresis. Diagnostic procedures include medical history and psychological screening with questionnaires, bladder and bowel diary, physical examination, urinalysis, ultrasound, and examination of residual urine. The mainstay of treatment is urotherapy with information and psychoeducation about normal lower urinary tract function, the underlying cause of MEN, disturbed bladder dysfunction in the child with NMEN and instructions about therapeutic strategies. Alarm therapy and the use of desmopressin have been shown to be effective in randomized trials. Children with NMEN first need treatment of the underlying daytime functional bladder problem before treatment of nocturnal enuresis. In patients with findings of overactive bladder, besides urotherapy, anticholinergic drugs may be useful.

Topics: Affective Symptoms; Biofeedback, Psychology; Child; Cholinergic Antagonists; Comorbidity; Deamino Arginine Vasopressin; Gastrointestinal Diseases; Humans; Nocturnal Enuresis; Patient Education as Topic; Problem Behavior; Psychometrics; Randomized Controlled Trials as Topic; Treatment Outcome; Ultrasonography; Urinalysis; Urinary Bladder; Urodynamics

This study is to compare the efficacy of enuresis alarm and desmopressin therapy in managing pediatric monosymptomatic enuresis. We performed systematic literature searches on different databases from inception until April 2017 without language restriction. All randomized control trials comparing an enuresis alarm and desmopressin in managing children with monosymptomatic enuresis were included. A total of 15 studies with 1502 participants (aged 5 to 16 years) were included for pooled analysis. Overall, an enuresis alarm outperformed desmopressin in achieving at least a partial response (>50% reduction in wet nights) in per-protocol analysis (OR: 1.53, 95% CI 1.05 to 2.23) but not in intention-to-treat analysis (OR: 0.97, 95% CI 0.73 to 1.30) as the alarm was hampered by a high dropout rate (OR: 2.20, 95% CI 3.41 to 4.29). However, alarm therapy yielded a better sustained response (OR: 2.89, 95% CI 1.38 to 6.04) and lower relapse rate (OR: 0.25, 95% CI 0.12 to 0.50). In the intention to treat analysis, the results revealed that alarm and desmopressin therapy are comparable in efficacy with regards to achieving >50% reduction in baseline wet nights in enuretic children. However, enuresis alarms offer a superior treatment response and a lower relapse rate in well-motivated children.

Topics: Child; Clinical Alarms; Deamino Arginine Vasopressin; Humans; Nocturnal Enuresis; Randomized Controlled Trials as Topic; Treatment Outcome

Most patients with monosymptomatic nocturnal enuresis can be effectively treated with an enuresis alarm or antidiuretic therapy (desmopressin), depending on the pathophysiology of the condition in the individual patient. Desmopressin is first-line therapy for enuresis caused by nocturnal polyuria, an excessive urine output during the night. However, in a recent study, around one-third of patients thought to be resistant to desmopressin were subsequently treated effectively with desmopressin monotherapy in a specialist centre. The aim of this article is to review best practice in selecting patients for desmopressin treatment, as well as outline eight recommendations for maximizing the chances of treatment success in patients receiving desmopressin. The roles of formulation, dose, timing of administration, food and fluid intake, inter-individual variation in response, body weight, adherence, withdrawal strategies and combination therapies are discussed in light of the most recent research on desmopressin and enuresis. Possible reasons for suboptimal treatment response are explored and strategies to improve outcomes in patients for whom desmopressin is an appropriate therapy are presented. Through optimization of the treatment plan in primary and specialist care centres, the hope is that fewer patients with this distressing and often embarrassing condition will experience unnecessary delays in receiving appropriate care and achieving improvements.

Topics: Antidiuretic Agents; Child; Deamino Arginine Vasopressin; Drug Administration Schedule; Female; Humans; Male; Medication Adherence; Nocturnal Enuresis; Treatment Outcome

Nocturnal enuresis (NE) is a common disorder in children. Choice of treatment depends on the frequency and severity of symptoms, the child's age and motivation. Treatment options for NE are alarm, desmopressin and imipramine. In particular, the main desmopressin therapeutical effect is the antidiuretic activity. The different formulations of desmopressin are an injectable solution, an oral tablet formulation and the recent oral lyophilisate (MELT). MELT with its higher biodisponibility guarantees the same therapy response of other formulations with a lower doses and it represents the first line and safety treatment for the NE.

Topics: Administration, Oral; Antidiuretic Agents; Child; Deamino Arginine Vasopressin; Humans; Italy; Nocturnal Enuresis; Prevalence; Treatment Outcome

Nocturnal polyuria in monosymptomatic nocturnal enuresis (MNE) has so far mainly been attributed to a disturbed circadian rhythm of renal water handling. Low vasopressin levels overnight correlate with absent maximal concentrating activity, resulting in an increased nocturnal diuresis with low urinary osmolality. Therefore, treatment with desmopressin is a rational choice. Unfortunately, 20 to 60 % of children with monosymptomatic enuresis are desmopressin-resistant. There is increasing evidence that other disturbed circadian rhythms might play a role in nocturnal polyuria. This review focuses on renal aspects in the pathophysiology of nocturnal polyuria in MNE, with special emphasis on circadian rhythms. Articles related to renal circadian rhythms and enuresis were searched through the PubMed library with the goal of providing a concise review.. Nocturnal polyuria can only partially be explained by blunted circadian rhythm of vasopressin secretion. Other alterations in the intrinsic renal circadian clock system also seem to be involved, especially in desmopressin-resistant enuresis.. • Disturbance in the circadian rhythm of arginine vasopressin secretion is related to nocturnal polyuria in children with enuresis. • Desmopressin is recommended as a treatment for monosymptomatic nocturnal enuresis, working as a vasopressin analogue acting on V2 receptors in the collecting ducts of the kidney. What is New: • Other renal circadian rhythms might play a role in nocturnal polyuria, especially in desmopressin-resistant case.

Topics: Antidiuretic Agents; Arginine Vasopressin; Child; Circadian Rhythm; Deamino Arginine Vasopressin; Humans; Kidney; Nocturnal Enuresis; Polyuria; Urinary Bladder; Urination

To investigate the efficacy of alarm therapy versus desmopressin therapy in treating primary mono-symptomatic nocturnal enuresis (PMNE).. PMNE is a common childhood disorder, which if left untreated can have a significant impact on a child's self-esteem and behaviour. Alarm therapy and desmopressin therapy are the two main treatments currently available in UK-based nurse-led enuresis clinics.. A systematic review of the literature was undertaken to assess the efficacy of PMNE treatments. Following application of inclusion/exclusion criteria eight randomised controlled/clinical trials were identified involving children aged 5-17 years with PMNE receiving either alarm therapy or desmopressin therapy.. Seven studies found no statistical difference in nocturnal continence improvement between the two interventions at the point when treatment was stopped. Four studies had a significantly larger relapse rate of nocturnal enuresis with desmopressin compared with alarm therapy when the treatment was withdrawn. Two papers reported that those participating in the alarm therapy intervention of the trials had a higher attrition rate than the desmopressin intervention. The overall findings from the eight studies showed that long term alarm therapy was more effective in treating nocturnal enuresis than desmopressin therapy. The review found that families and children receiving the alarm therapy intervention require more support from health care professionals to comply with treatment than those receiving the desmopressin therapy. However, if nurse-led clinics can support families to persist with the alarm therapy intervention, they are more likely to experience longer term improvement in continence.

Topics: Adolescent; Antidiuretic Agents; Child; Child, Preschool; Clinical Alarms; Deamino Arginine Vasopressin; Humans; Nocturnal Enuresis; Treatment Outcome

Nocturnal enuresis is a prevalent and challenging problem in children and young adults with sickle cell disease (SCD). Limited progress has been made in elucidating etiology and pathophysiology of nocturnal enuresis in individuals with SCD. Among adults with SCD ages 18-20 years, approximately 9% report nocturnal enuresis. Nocturnal enuresis contributes to decreased health related quality of life in people with SCD, resulting in low self-esteem and sometimes social isolation. Postulated non-mutually exclusive causes of nocturnal enuresis in individuals with SCD include hyposthenuria leading to nocturnal polyuria, decreased bladder capacity or nocturnal bladder overactivity, increased arousal thresholds, and sleep disordered breathing. No evidence-based therapy for nocturnal enuresis in SCD exists. This review is focused on describing the natural history, postulated causes and a rational approach to the evaluation and management of nocturnal enuresis in children and adults with SCD.

Topics: Anemia, Sickle Cell; Antidiuretic Agents; Brain; Cholinergic Antagonists; Deamino Arginine Vasopressin; Humans; Nocturnal Enuresis; Quality of Life; Sleep Apnea Syndromes; Urinary Bladder

The aim of this article is to review International Children's Continence Society guidelines on the recommended diagnostic evaluation and therapy for children with nocturnal enuresis. Nocturnal enuresis (NE) is the condition describing the symptom of wetting during sleep above the age of 5 years. NE is one of the most common disorders among children. Enuresis is characterised as monosymptomatic nocturnal enuresis (MNE) if there are no additional voiding problems. Children with other daytime symptoms (daytime incontinence, urgency, frequency) and nocturnal enuresis are said to have non-monosymptomatic nocturnal enuresis (NMNE). A careful medical history, including bladder diary, physical examination, urinalysis, an ultrasound of the urinary tract system will usually provide sufficient information for the physician to arrive at a diagnosis. Urodynamic, radiologic and endoscopic evaluation are not necessary in children with monosymptomatic nocturnal enuresis. Two first line treatment options of MNE are currently recommended: nonpharmacologic treatment and pharmacologic treatment (desmopressin). Nonpharmacologic treatment of enuresis includes motivational therapy, bladder-training exercises, fluid and food intake and enuresis alarm. Before using alarm treatment or desmopressin, simple therapeutic interventions should be considered. Children with nocturnal poliuria and normal bladder capacity will be more sensitive to desmopressin.

Topics: Antidiuretic Agents; Behavior Therapy; Child, Preschool; Deamino Arginine Vasopressin; Humans; Nocturnal Enuresis; Physical Examination; Practice Guidelines as Topic

Topics: Adult; Antidepressive Agents, Tricyclic; Antidiuretic Agents; Behavior Therapy; Child; Child, Preschool; Cholinergic Antagonists; Complementary Therapies; Deamino Arginine Vasopressin; Female; Humans; Imipramine; Male; Medical History Taking; Monitoring, Physiologic; Nocturnal Enuresis; Psychotherapy; Quality of Life; Referral and Consultation; Treatment Outcome

This document represents the consensus guidelines recommended by the ICCS on how to evaluate and treat children with nonmonosymptomatic nocturnal enuresis (NMNE). The document is intended to be clinically useful in primary, secondary and tertiary care.. Discussions were held by the board of the ICCS and a committee was appointed to draft this document. The document was then made available to the members of the society on the web site. The comments were vetted and amendments were made as necessary to the document.. The main scope of the document is the treatment of NMNE with drugs other than desmopressin-based therapy. Guidelines on the assessment, and nonpharmacologic and pharmacologic management of children with NMNE are presented.. The text should be regarded as an expert statement, not a formal systematic review of evidence-based medicine. It so happens that the evidence behind much of what we do in the care of enuretic children is quite weak. We do, however, intend to present what evidence there is, and to give preference to this rather than to experience-based medicine, whenever possible.

Topics: Antidiuretic Agents; Botulinum Toxins, Type A; Child; Deamino Arginine Vasopressin; Diurnal Enuresis; Electric Stimulation Therapy; Humans; Neuromuscular Agents; Nocturnal Enuresis; Practice Guidelines as Topic

Nocturnal enuresis, or bedwetting, is the most common cause of urinary incontinence in children. It is known to have a significant psychosocial impact on the child as well as the family. Nocturnal enuresis typically presents as failure to become dry at night after successful daytime toilet training. It can be primary or secondary (developing after being successfully dry at night for at least 6 months). Children with nocturnal enuresis may have excessive nocturnal urine production, poor sleep arousal and/or reduced bladder capacity. Alarm therapy is the recommended first-line therapy, with treatment choices being influenced by the presence or absence of the abnormalities mentioned above. Children with nocturnal enuresis may also have daytime urinary urgency, frequency or incontinence of urine. This group (non-monosymptomatic nocturnal enuresis) requires a different clinical approach, with a focus on treating daytime bladder symptoms, which commonly involves pharmacotherapy with anticholinergic medications and urotherapy (including addressing bowel problems). This review discusses the current management of nocturnal enuresis using the terminologies recommended by the International Children's Continence Society.

Topics: Algorithms; Anti-Inflammatory Agents, Non-Steroidal; Antidepressive Agents, Tricyclic; Antidiuretic Agents; Behavior Therapy; Child; Child, Preschool; Cholinergic Antagonists; Deamino Arginine Vasopressin; Humans; Imipramine; Mandelic Acids; Neurophysins; Nocturnal Enuresis; Protein Precursors; Risk Factors; Vasopressins

Topics: Antidiuretic Agents; Child; Deamino Arginine Vasopressin; Female; Humans; Male; Nocturnal Enuresis

Vasopressin V(2) agonists are well known as effective therapies in the treatment of central diabetes insipidus and nocturnal enuresis. Furthermore, given their mode of action, these particular agonists have more recently been considered, in both the pharmaceutical industry and in academia, as viable therapies for urological conditions such as nocturia.. For the past 10 years, significant progress has been made in the discovery and development of vasopressin V(2) agonists. This article provides the reader with information on the recent progress in the discovery and development of these compounds based on patents published from 2002 onward. Specifically, the article looks at the discovery of new non-peptide agonists as well as well as novel formulations of the vasopressin V(2) agonist desmopressin.. The V(2) receptor is currently one of the hottest therapeutic targets investigated for the treatment of urinary disorders such as nocturia and central diabetes. Over the past 10 years, significant progress has been made in the discovery and development of vasopressin V(2) receptor agonists, for the treatment of these disorders. The author anticipates that these agonists will be launched to market in the not-too-distant future.

Topics: Animals; Arginine Vasopressin; Deamino Arginine Vasopressin; Diabetes Insipidus; Drug Design; Humans; Molecular Structure; Nocturnal Enuresis; Patents as Topic; Receptors, Vasopressin; Structure-Activity Relationship

Urinary incontinence (bedwetting, enuresis) is the commonest urinary symptom in children and adolescents and can lead to major distress for the affected children and their parents. Physiological and non-physiological types of urinary incontinence are sometimes hard to tell apart in this age group.. This article is based on selected literature retrieved by a PubMed search and on an interdisciplinary expert consensus.. Nocturnal enuresis has a variety of causes. The main causative factors in monosymptomatic enuresis nocturna (MEN) are an impaired ability to wake up when the bladder is full, due to impaired or absent perception of fullness during sleep, and an imbalance between bladder capacity and nocturnal urine production. On the other hand, non-monosymptomatic enuresis nocturna (non-MEN) is usually traceable to bladder dysfunction, which is also the main cause of diurnal incontinence. A basic battery of non-invasive diagnostic tests usually suffices to determine which type of incontinence is present. Further and more specific testing is indicated if an organic cause is suspected or if the treatment fails. The mainstay of treatment is urotherapy (all non-surgical and non-pharmacological therapeutic modalities). Some patients, however, will need supportive medication in addition. Urinary incontinence has different causes in children and adults and must therefore be diagnosed and treated differently as well. All physicians who treat the affected children (not just pediatricians and family doctors, but also pediatric nephrologists, urologists, pediatric surgeons, and child psychiatrists) must be aware of the specific features of urinary incontinence in childhood.

Topics: Adolescent; Antidiuretic Agents; Behavior Therapy; Benzilates; Child; Deamino Arginine Vasopressin; Diagnosis, Differential; Diurnal Enuresis; Evidence-Based Medicine; Female; Humans; Male; Nocturnal Enuresis; Parasympatholytics; Practice Guidelines as Topic; Urodynamics

Nocturnal enuresis (bedwetting) is a socially disruptive and stressful condition which affects around 15% to 20% of five year olds, and up to 2% of young adults.. To assess the effects of complementary interventions and others such as surgery or diet on nocturnal enuresis in children, and to compare them with other interventions.. We searched PubMed (1950 to June 2010), EMBASE (1980 to June 2010), the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS) (1984 to June 2010), Chinese Biomedical Literature Database (CBM) (1975 to June 2010), China National Knowledge Infrastructure (CNKI) (1979 to June 2010), VIP database (1989 to June 2010), and the reference lists of relevant articles, all last searched 26 June 2010. No language restriction was used.. All randomised or quasi-randomised trials of complementary and other miscellaneous interventions for nocturnal enuresis in children were included except those focused solely on daytime wetting. Comparison interventions could include no treatment, placebo or sham treatment, alarms, simple behavioural treatment, desmopressin, imipramine and miscellaneous other drugs and interventions.. Two reviewers independently assessed the quality of the eligible trials, and extracted data.. In 24 randomised controlled trials, 2334 children were studied, of whom 1283 received a complementary intervention. The quality of the trials was poor: 5 trials were quasi-randomised, 5 showed differences at baseline and 17 lacked follow up data.The outcome was better after hypnosis than imipramine in one trial (relative risk (RR) for failure or relapse after stopping treatment 0.42, 95% confidence interval (CI) 0.23 to 0.78). Psychotherapy appeared to be better in terms of fewer children failing or relapsing than both alarm (RR 0.28, 95% CI 0.09 to 0.85) and rewards (RR 0.29, 95%CI 0.09 to 0.90) but this depended on data from only one trial. Medicinal herbs had better results than desmopressin in one trial (RR for failure or relapse after stopping treatment 0.35, 95% CI 0.14 to 0.85). Acupuncture had better results than sham control acupuncture (RR for failure or relapse after stopping treatment 0.67, 95% CI 0.48 to 0.94) in a further trial. Active chiropractic adjustment had better results than sham adjustment (RR for failure to improve 0.76, 95% CI 0.60 to 0.95). However, each of these findings came from small single trials, and must be verified in further trials. The findings for diet and faradization were unreliable, and there were no trials including homeopathy or surgery.. There was weak evidence to support the use of hypnosis, psychotherapy, acupuncture, chiropractic and medicinal herbs but it was provided in each case by single small trials, some of dubious methodological rigour. Robust randomised trials are required with efficacy, cost-effectiveness and adverse effects clearly reported.

Topics: Acupuncture Therapy; Child; Complementary Therapies; Counseling; Deamino Arginine Vasopressin; Electric Stimulation Therapy; Homeopathy; Humans; Hypnosis; Manipulation, Chiropractic; Nocturnal Enuresis; Psychotherapy; Randomized Controlled Trials as Topic; Renal Agents

Topics: Antidepressive Agents, Tricyclic; Antidiuretic Agents; Behavior Therapy; Child; Cholinergic Antagonists; Constipation; Deamino Arginine Vasopressin; Humans; Male; Nocturnal Enuresis; Polyuria

Topics: Antidiuretic Agents; Behavior Therapy; Child; Deamino Arginine Vasopressin; Diurnal Enuresis; Dose-Response Relationship, Drug; Humans; Nocturnal Enuresis; Physical Examination; Urinary Bladder, Neurogenic; Urodynamics

Desmopressin acetate is the synthetic analogue of the antidiuretic hormone arginine vasopressin. It has been employed clinically for >30 years in a range of formulations: intranasal solution (since 1972), injectable solution (since 1981), tablets (since 1987), and most recently, an oral lyophilisate (since 2005). The antidiuretic properties of desmopressin have led to its use in polyuric conditions including primary nocturnal enuresis, nocturia, and diabetes insipidus. While a large body of clinical data is available for desmopressin, and despite its widespread use, comprehensive reviews of the safety of desmopressin are lacking (although some case series have attempted to correlate patient and/or dosing characteristics with the occurrence of adverse reactions). The purpose of this paper is to review the safety of desmopressin, based on analyses of both published data (MedLine) and of adverse reactions reported to Ferring Pharmaceuticals, the major manufacturer of desmopressin. Based on the findings, suggested strategies to reduce the risk of adverse reactions are proposed. Treatment with intranasal and oral formulations of desmopressin is generally well tolerated, and side effects are usually minor. The risk of hyponatraemia, although small, can be reduced by adhering to the indications, dosing recommendations and precautions when prescribing desmopressin.

Topics: Adverse Drug Reaction Reporting Systems; Antidiuretic Agents; Clinical Trials as Topic; Deamino Arginine Vasopressin; Humans; Hyponatremia; Nocturia; Nocturnal Enuresis; Risk Factors

Abnormalities of micturition occur in many different diseases, have a variety of causes and take several forms. This review will focus exclusively on those abnormalities in which antidiuretic therapy may be of benefit. These conditions are primarily characterized by an increase in the total amount of urine produced (polyuria) or a circadian shift in the control of urine production and/or voiding (nocturnal enuresis, nocturia).

Topics: Antidiuretic Agents; Deamino Arginine Vasopressin; Humans; Nocturnal Enuresis; Polyuria; Quality of Life; Urination Disorders; Water

Monosymptomatic nocturnal enuresis, a heterogeneous condition, is frequently treated in children aged >5 years. Of the various treatment options, enuresis alarm has been widely advocated as being effective for treating nocturnal enuresis, while extracorporeal pelvic floor magnetic stimulation for overactive bladder, urge incontinence and urgency-frequency syndrome has not yet been confirmed by controlled studies as primary treatment for monosymptomatic nocturnal enuresis. Desmopressin, an antidiuretic hormone (ADH) analog, or arginine vasopressin (AVP), can resolve primary nocturnal enuresis by decreasing night-time urine production. Enuretic children requiring either desmopressin or desmopressin plus oxybutynin to achieve dryness have polyuria. Tricyclic antidepressants (i.e. imipramine) are used successfully in enuretic children. Although tricyclics and desmopressin are effective in reducing the number of wet nights, most children relapse after discontinuation of active treatment. Combined therapy (enuresis alarm, bladder training, motivational therapy and pelvic floor muscle training) is more effective than each component alone or than pharmacotherapy. Furthermore, desmopressin combined with alarm therapy has a positive effect on enuresis. Pharmacotherapy can provide early relief of enuresis, while behavioral intervention may lead to greater long-term benefits. The positive effect of achieving dry nights with pharmacotherapy can encourage the child to sustain behavioral therapy.

Topics: Antidiuretic Agents; Arginine Vasopressin; Behavior Therapy; Child; Child, Preschool; Deamino Arginine Vasopressin; Drug Therapy, Combination; Exercise Therapy; Humans; Mandelic Acids; Motivation; Nocturnal Enuresis; Parasympatholytics; Toilet Training; Treatment Outcome; Urodynamics

Desmopressin is a well established and effective therapy for nocturnal enuresis. Water intoxication leading to hyponatremia is an infrequent but serious adverse event associated with desmopressin. We assessed the safety of desmopressin in children 18 years or younger with nocturnal enuresis with a focus on the relative safety of the oral compared with the intranasal formulation.. Published data (MEDLINE) from December 1972 to August 2006 and post-marketing safety data from December 1972 to June 2005 were analyzed.. A total of 21 clinical trials on desmopressin use in children with nocturnal enuresis were identified. There were no reports of hyponatremia. A total of 21 publications were identified that included 48 case reports of hyponatremia in children with nocturnal enuresis. In all case reports patients were treated with intranasal desmopressin. Post-marketing safety data included 151 cases of hyponatremia in children with nocturnal enuresis, of whom 145 were treated with intranasal desmopressin and 6 were treated with the tablet formulation. Prodromal symptoms of hyponatremia were identified as headache, nausea and vomiting.. Data suggest that there is a decreased risk of hyponatremia with oral desmopressin compared with intranasal desmopressin. Identifiable and preventable risk factors for hyponatremia are inappropriately high fluid intake, administration of a larger than recommended dose, young age (less than 6 years) and concomitant administration of another medication. When desmopressin is prescribed, patients should be instructed to avoid high fluid intake when the medication is ingested, not ingest a higher than recommended dose and promptly discontinue the medication and seek assessment if headache, nausea or vomiting develops.

Topics: Administration, Intranasal; Administration, Oral; Antidiuretic Agents; Child; Deamino Arginine Vasopressin; Humans; Hyponatremia; Nocturnal Enuresis; Osmolar Concentration; Risk Factors

Nocturnal enuresis (NE) is one of the most frequent paediatric pathologies. The prevalence of primary nocturnal enuresis (PNE) is around 9% in children between 5 and 10 years of age and about 40% of them have one or more episodes per week. Still for too long, PNE has not been recognised as a pathological condition, particularly by the medical community; as a consequence, there was no specific education at medical school, and a poor involvement by the practitioners. Enuretic children have a sense of social difference and isolation; some of them do express a low self-esteem. Also, self-esteem is improved by the management NE even if this management fails to cure the condition. Primary monosymptomatic nocturnal enuresis (PMNE) is an heterogeneous condition for which various causative factors have been identified such as: nocturnal polyuria, sleep disturbances, reduced bladder capacity or bladder dysfunction, upper airway obstruction. The positive diagnosis of PMNE is based on a complete questionnaire and a careful physical examination. A drinking and voiding chart is an essential non-invasive tool: first, to collect information about the initial drinking and voiding habits of the child, then to reassess the accuracy of the diagnosis. Only motivated patients should receive a specific treatment for their NE and the treatment should be proposed based on the type of PMNE. PMNE associated with nocturnal polyuria should be treated with desmopressin, which reduces nighttime urine production. For PMNE with a reduced bladder capacity alarms should be the first-line treatment. Oxybutinin, a drug with anticholinergic properties, is not theoretically indicated for the treatment of PMNE except for a very small subgroup of patients who have an overactive bladder only during sleep. In cases refractory to monotherapy, NE is probably the result of an association of different physiopathological factors (e.g. both a nocturnal polyuria together with a small bladder capacity) some of them are still unknown. In these patients, a combination of treatments may be more effective than monotherapy. Various combination therapies can be proposed to improve the cure rates.

Topics: Adolescent; Antidiuretic Agents; Child; Combined Modality Therapy; Deamino Arginine Vasopressin; Humans; Nocturnal Enuresis

Bedwetting (nocturnal enuresis) is not uncommon in childhood but it can have a profound effect on children and their families. Parents sometimes avoid seeking help due to feelings of shame or embarrassment, or because they believe that nothing can be done and they must wait for their child to "grow out of it". For some children this may take many years and one in 50-100 will reach their teens without becoming dry. There is evidence that effective intervention can reduce the duration of the problem and help to improve the lives of children and their families. An individual assessment is the key to successful treatment, as well as practical suggestions to help families to manage the situation and therefore reduce the stress it may cause. The primary health care professional is ideally placed to offer this support and to encourage families to come forward to discuss the problem. This article gives an overview of current treatment practice and outlines the information and support that health professionals can give to parents and carers.

Topics: Antidiuretic Agents; Causality; Child; Deamino Arginine Vasopressin; Health Education; Humans; Mandelic Acids; Muscarinic Antagonists; Nocturnal Enuresis; Nurse's Role; Nursing Assessment; Parents; Patient Selection; Pediatric Nursing; Primary Health Care; Referral and Consultation; Social Support; Toilet Training; United Kingdom

Topics: Adolescent; Antidepressive Agents, Tricyclic; Antidiuretic Agents; Child; Deamino Arginine Vasopressin; Humans; Nocturnal Enuresis

Monosymptomatic enuresis (MNE) results from a pathogenic triad that may include lack of vasopressin secretion during sleep, reduced functional bladder capacity and inability to wake up during sleep. The treatment of MNE can be performed through behavioral therapy, use of alarms or medications such as desmopressin and imipramine.. To compare the effectiveness of different treatments of MNE.. Prospective and randomized study comparing different intervention and a control group (receiving only behavior therapy) for MNE.. age between 5 and 16 years old, with MNE, evaluated at the pediatric urology outpatient clinic of Hospital Infantil Menino Jesus. At first visit children were submitted to behavior therapy (urotherapy) for 3 months, children were subsequently characterized according to the ICCS as non-responders, partial responders, or full responders. Those partial responders or non-responders received a patient ID and were randomized to four groups: Alarm Group (G1), Desmopressin Group - DDAVP (G2), Imipramine Group (G3) and Control (G4). All groups were monitored monthly, for a period of 6 months. After 6 months, the children were reevaluated for MNE.. 93 patients were enrolled. Mean age was 10.96 years with a standard deviation of 2.28 years, 59,1% were male. All groups had improvement in the number of dry nights (Table). Taking in account success the population full responders and partial responders: Alarm Group (G1) achieve success in 100% of cases, Desmopressin Group - DDAVP (G2) in 63.6% of cases, Imipramine Group (G3) in 73.7% of cases (Table 3). No drugs side effects were observed in both groups (G2 and G3), there was no dropout in patients who used alarms.. Our data suggests that the use of alarms is the most effective treatment of ENM with superior results when compared to imipramine and DDAVP. The small number of participants is a weakness of the study, as well as the lack of a voiding diary at the end of the study.. All therapeutics options utilized in the treatment of MNE are safe, effective and has a low rate of abandonment.

Topics: Adolescent; Child; Child, Preschool; Deamino Arginine Vasopressin; Enuresis; Female; Humans; Imipramine; Male; Nocturnal Enuresis; Prospective Studies; Treatment Outcome

To compare the efficacy and tolerability of Solifenacin plus Desmopressin and Desmopressin alone in the treatment of primary monosymptomatic nocturnal enuresis (PMNE).. A total of 88 children, 5-14 years old, diagnosed with PMNE were enrolled in this randomized control trial (RCT) from June 2017 to June 2020. After informed written consent patients were randomized to one of the two therapeutic groups. Group 1 received one puff of desmopressin nasal spray 1 h before bedtime every night. Group 2 received one pill of solifenacin 5 mg plus one puff of desmopressin nasal spray 1 h before bedtime every night. All patients were evaluated after three months for their response to treatment and drug side effects.. The mean age in desmopressin alone group and solifenacin plus desmopressin group was 8.1 ± 2.2 (5-14) and 7.9 ± 2.2 (5-14) years respectively (p-value >0.05). In group 2, 37/44 (84.09%) patients achieved complete response after three months of treatment in comparison to group 1 in which 27/44 (61.36%) patients showed complete response (p-value <0.05). In group 1, 8/44 (18.18%) patients developed treatment related side effects whereas in group 2, 12/44 (27.27%) patients developed side effects (p-value >0.05). No case of discontinuation of treatment due to side effects was observed in any of the two groups. The recurrence rate was also significantly lower in group 2 in comparison to group 1 (8.1% vs 33.3%, p-value <0.05).. Our study demonstrated that the combination of Solifenacin plus Desmopressin is more effective than desmopressin monotherapy in the treatment of PMNE with an acceptable tolerability profile.. Level I.

Topics: Adolescent; Child; Child, Preschool; Deamino Arginine Vasopressin; Humans; Nasal Sprays; Nocturnal Enuresis; Solifenacin Succinate

To compare the efficacy of desmopressin plus tolterodine (D+T) with desmopressin plus indomethacin (D+I) for treating enuresis in children.. Open-label randomized controlled trial.. Bandar Abbas Children's Hospital, a tertiary care children's hospital in Iran, from March 21, 2018, to March 21, 2019.. 40 children older than five years with monosymp-tomatic and non-monosymptomatic primary enuresis resistant to desmopressin monotherapy.. Patients were randomized to receive either D+T (60 µg sublingual desmopressin and 2 mg tolterodine) or D+I (60 µg sublingual desmopressin and 50 mg indomethacin) every night before bedtime for five months.. Reduction in the frequency of enuresis was evaluated at one, three, and five months, and response to treatment at five months. Drug reactions and complications were also noted.. After adjustment for age, consistent incontinence from toilet training, and non-monosymptomatic enuresis, D+T was significantly more efficacious than D+I; mean (SD) percent in nocturnal enuresis reduction at 1 [58.86 (7.27)% vs 31.18 (3.85) %; P<0.001], 3 [69.78 (5.99) % vs 38.56 (3.31) %; P<0.000], and 5 [84.84(6.21) % vs 39.14 (3.63) %; P<0.001] months showing a large effect. At 5 months, complete response to treatment was only observed with D+T, while treatment failure was significantly higher with D+I (50% vs 20%; P=0.047). None of the patients in either group developed cutaneous drug reactions or central nervous system symptoms.. Desmopressin plus tolterodine appears to be superior to desmopressin plus indomethacin for treating pediatric enuresis resistant to desmopressin.

Topics: Child; Child, Preschool; Deamino Arginine Vasopressin; Drug Therapy, Combination; Humans; Indomethacin; Nocturnal Enuresis; Tolterodine Tartrate

Topics: Antidiuretic Agents; Deamino Arginine Vasopressin; Enuresis; Humans; Imipramine; Nocturnal Enuresis; Prospective Studies

Topics: Antidiuretic Agents; Deamino Arginine Vasopressin; Humans; Imipramine; Nocturnal Enuresis; Prospective Studies

We investigated the efficacy and safety of fluoxetine, a selective serotonin reuptake inhibitor, for treating refractory primary monosymptomatic nocturnal enuresis in children.. 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.. 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 (. Fluoxetine is safe treatment for refractory primary monosymptomatic nocturnal enuresis in children with good initial response that declines at 12 weeks.

Topics: Adolescent; Child; Cholinergic Antagonists; Deamino Arginine Vasopressin; Fluoxetine; Humans; Nocturnal Enuresis; Selective Serotonin Reuptake Inhibitors

To study the pharmacokinetic (PK)/pharmacodynamic (PD) characteristics of desmopressin (dDAVP) oral lyophilisate in children below the age of 8 years with special emphasis on age-related and size-related differences in bioavailability.. Open label, non-randomised, interventional PK and PD trial.. Single-centre study.. Children (age: 6 months to 8 years) with nocturnal polyuria, including both children with uropathy or nephropathy (glomerular filtration rate >60 mL/min/1.73 m²) and children (age: 5-8 years) with severe monosymptomatic nocturnal enuresis, who were unresponsive to treatment with 400 µg of the dDAVP tablet for at least 1 month.. After a water load, dDAVP was administered sublingually as a single dose of oral lyophilisate. Subsequently, blood and urine samples were collected until 7 hours post-administration.. Non-compartmental analysis of PK parameters was performed based on dDAVP concentrations in both plasma and urine. To evaluate the effect of dDAVP lyophilisate (PD parameters), the urinary concentration capacity (urine osmolality (mOsm/kg)) and antidiuretic effect (diuresis rate (mL/kg/h)) were calculated.. For the first time, a double absorption profile of dDAVP lyophilisate was found in children, questioning extrapolation of bioequivalence from adults towards children. Moreover, the need for size-adapted dosing regimens of dDAVP lyophilisate in young children is indicated.. NTC02584231.

Topics: Administration, Oral; Antidiuretic Agents; Biological Availability; Child; Child, Preschool; Deamino Arginine Vasopressin; Female; Humans; Infant; Male; Nocturnal Enuresis; Tablets; Therapeutic Equivalency

Nocturnal enuresis is a common disease of childhood. It can be classified into monosymptomatic nocturnal enuresis (MNE) or nonmonosymptomatic nocturnal enuresis (NMNE). Imipramine is a tricyclic antidepressant used to treat enuresis with initial success rates are high as 50% but some studies record a high relapse rate and it has a cardiotoxic effect when overdosed. Anticholinergics may be effective in the treatment of children with bladder storage dysfunction, including daytime incontinence. However, anticholinergics monotherapy is not effective in treating MNE. In our study, we used a low dose (25 mg) of imipramine in order to avoid its potential side effects and combined it with the synergistic anticholinergic action of solifenacin. Our objective was to evaluate the efficacy and safety of the combination of solifenacin and imipramine compared with placebo in the treatment of desmopressin refractory MNE.. One hundred children aged 6 years or more with primary MNE unresponsive to desmopressin treatment were included. The children were randomly divided into two equal groups. Group A received imipramine 25 mg and solifenacin 5-10 mg oral tablets and group B received placebo once 1 h before bedtime for 3 months. The primary end point was to investigate the efficacy of the combined treatment of solifenacin and imipramine and the secondary end point was the safety of the drugs.. Our study showed that the mean post treatment wet nights per month was significantly lesser in the treatment group than placebo group (. The combination treatment of solifenacin and imipramine is a useful and safe treatment for nocturnal enuresis after failure of everything else.

Topics: Child; Deamino Arginine Vasopressin; Humans; Imipramine; Nocturnal Enuresis; Prospective Studies; Solifenacin Succinate

To assess the efficacy of desmopressin plus anticholinergic combination therapy as first-line treatment for children with primary monosymptomatic nocturnal enuresis (PMNE) and to analyze this combination's effect on functional bladder capacity (FBC).. A total of 99 children with PMNE were prospectively enrolled from 2015 to 2019 and randomly allocated to a monotherapy group (n=49), with oral desmopressin lyophilisate (MELT) only; and a combination group (n=50), with desmopressin plus an anticholinergic (propiverine 5 mg). Efficacy and FBC were evaluated at 1 and 3 months after treatment initiation; the relapse rate was assessed at 6 months after treatment cessation.. The combination therapy group showed a higher rate of complete response than the monotherapy group after 3 months of treatment (44.0% vs. 22.4%, p=0.002). A significant increase in mean FBC was observed only in the combination group, from 88.72±26.34 mL at baseline to 115.52±42.23 mL at 3 months of treatment (p=0.024). Combination therapy was significantly associated with treatment success at 3 months after treatment initiation (odds ratio [OR], 3.527; 95% confidence interval [CI], 1.203-6.983; p=0.011) and decreased risk of relapse at 6 months after treatment cessation (OR, 0.306; 95% CI, 0.213-0.894; p=0.021), by multivariable analysis.. This study represents the first prospective, randomized controlled trial showing higher response rates and lower relapse rates with desmopressin plus anticholinergic combination therapy compared with desmopressin monotherapy as first-line treatment for children with PMNE.

Topics: Antidiuretic Agents; Benzilates; Child; Deamino Arginine Vasopressin; Drug Therapy, Combination; Female; Humans; Male; Muscarinic Antagonists; Nocturnal Enuresis; Prospective Studies; Recurrence; Treatment Outcome

The bioequivalence of two formulations of desmopressin (dDAVP), a vasopressin analogue prescribed for nocturnal enuresis treatment in children, has been previously confirmed in adults but not in children. In this study, we aimed to study the pharmacokinetics (PK) and pharmacodynamics (PD) of these two formulations, in both fasted and fed children, including patients younger than 6 years of age.. Previously published data from one PK study and one PK/PD study in children aged between 6 and 16 years were combined with a new PK/PD study in children aged between 6 months and 8 years, and analysed using population PK/PD modelling. Simulations were performed to further explore the relative bioavailability of both formulations and evaluate current dosing strategies.. The complex absorption behaviour of the lyophilizate was modelled using a double input, linked to a one-compartmental model with linear elimination and an indirect response model linking dDAVP concentration to produced urine volume and osmolality. The final model described the observed data well and elucidated the complexity of bioequivalence and therapeutic equivalence of the two formulations. Simulations showed that current dosing regimens using a fixed dose of lyophilizate 120 μg is not adequate for children, assuming children to be in the fed state when taking dDAVP. A new age- and weight-based dosing regimen was suggested and was shown to lead to improved, better tailored effects.. Bioequivalence and therapeutic equivalence data of two formulations of the same drug in adults cannot be readily extrapolated to children. This study shows the importance of well-designed paediatric clinical trials and how they can be analysed using mixed-effects modelling to make clinically relevant inferences. A follow-up clinical trial testing the proposed dDAVP dosing regimen should be performed.. This trial has been registered at www.clinicaltrials.gov (identifier NCT02584231; EudraCT 2014-005200-13).

Topics: Adolescent; Antidiuretic Agents; Biological Availability; Child; Child, Preschool; Computer Simulation; Deamino Arginine Vasopressin; Double-Blind Method; Drug Compounding; Fasting; Female; Humans; Infant; Male; Models, Biological; Nocturnal Enuresis; Osmolar Concentration; Therapeutic Equivalency

Nocturnal enuresis is a condition, which can affectthe quality of life in children. The present study was designed toinvestigate the efficacy of low-dose imipramine combined withdesmopressin on treatment of patients with primary nocturnalenuresis who were defined as desmopressin non-responders.. A randomized clinical trial was carried out on patientswith primary nocturnal enuresis. Forty children with enuresisranging from 5 to 12 years old were randomly divided into theintervention (n = 20) and control groups (n = 20). The subjects inthe intervention group were treated with desmopressin combinedwith 5 mg imipramine at bedtime, and those in the control groupwere given desmopressin alone. The patients were followed upweekly for one month. The number of wet nights was recorded.. Two individuals in the intervention and three individualsin the control group were excluded from the study. Our findingsindicated that the age and gender showed no significant difference.Furthermore, a significant better recovery in the enuresis wasobserved in 18 of 20 patients who were treated with combinationtherapy after 1 month (P < .05). In addition, the frequency ofrecovery was significantly higher (83.3%) in the intervention group,compared with the control group (29.4%).. The analysis showed that low-dose imipramine is welltolerated in clinical practice and may represent a good short-termtreatment option in combination therapy where desmopressinalone is not efficient enough.

Topics: Antidiuretic Agents; Child; Child, Preschool; Deamino Arginine Vasopressin; Drug Therapy, Combination; Female; Humans; Imipramine; Male; Nocturnal Enuresis; Treatment Outcome

For a new formulation of a drug, only pharmacokinetic bioequivalence with the original formulation has to be demonstrated in healthy, young adults. However, "children are not small adults," and to guarantee a safe and effective treatment, age-adapted drug development is required. Desmopressin, a vasopressin analogue prescribed for nocturnal enuresis in children, was studied as an example formulation first developed in adults and then extrapolated to a pediatric indication.. Population pharmacokinetic and pharmacodynamic modeling was used to analyze previously published desmopressin data of 18 children suffering from nocturnal enuresis. The main objective was the comparison of the therapeutic equivalence of two desmopressin formulations: tablet and lyophilisate. The measurements for pharmacokinetics and pharmacodynamics were respectively plasma desmopressin concentration and urine osmolality and diuresis.. The half maximal inhibitory concentration for inhibition of urine production was 0.7 pg/mL lower for the lyophilisate than for the tablet. The effect of formulation on the half maximal inhibitory concentration seems to suggest that the 120-μg lyophilisate has a more pronounced effect on the urine volume and osmolality than the 200-μg tablet, even when the same exposure is achieved.. A new indirect response model for desmopressin was constructed and validated, using a previously built pharmacokinetic model and additional pharmacodynamic data. In order to draw solid conclusions regarding the efficacy and safety of desmopressin in children, pharmacokinetics and pharmacodynamics data should be analyzed together. This study adds proof to potential differences in pediatric and adult pharmacokinetic and pharmacodynamic properties of desmopressin and exemplifies the need for pediatric clinical trials, not only for every new drug but also for every new formulation.

Topics: Administration, Sublingual; Adolescent; Age Factors; Antidiuretic Agents; Child; Cross-Over Studies; Deamino Arginine Vasopressin; Drug Compounding; Female; Freeze Drying; Humans; Kidney Concentrating Ability; Male; Models, Biological; Needs Assessment; Nocturnal Enuresis; Osmolar Concentration; Pilot Projects; Tablets; Urinalysis

To compare the frequency of spina bifida occulta (SBO) detected in patients with nocturnal enuresis (NE) and to investigate its clinical significance.. Patients aged 6 to 15 years who were admitted to the urology clinic with NE were included in this prospective study. The control group consisted of patients who were admitted with a complaint of abdominal or lateral pain. The patients who had lower urinary tract symptoms (LUTS) were classified as nonmonosymptomatic NE (NMNE). Those with monosymptomatic NE were treated with desmopressine. In patients with NMNE, treatment with oxybutynin was added if an overactive bladder or uninhibited contraction was detected by urodynamics.. A total of 184 NE and 180 control patients were included in the study. SBO was detected in 71 (19.5%) patients and LUTS in 100 (27.4%). When the groups with and without NE were compared, the number of patients with SBO (26% vs 17%, P = .044) and those with LUTS (36% vs 17.5%, P < .001) were significantly higher in the NE group. The overall rate of dryness (67.4% vs 83.6%, P = .024) and response to LUTS treatment (65% vs 97%, P < .01) were significantly lower in those with SBO than in those without SBO.. SBO is more common in NE patients than in non-NE patients. Response to NE treatment is lower in SBO patients with severe LUTS; for this population, advanced treatment options may be considered earlier.

Topics: Antidiuretic Agents; Child; Deamino Arginine Vasopressin; Female; Humans; Lower Urinary Tract Symptoms; Male; Mandelic Acids; Nocturnal Enuresis; Prospective Studies; Spina Bifida Occulta; Treatment Outcome; Urodynamics; Urological Agents

Desmopressin is a synthetic V2 specific analogue of antidiuretic hormone (arginine vasopressin) that is widely used as first line treatment for monosymptomatic nocturnal enuresis. However, no biomarkers to predict desmopressin effectiveness have yet been established. Because arginine vasopressin is unstable, we prospectively measured the major urine concentration factor aquaporin 2 and serum copeptin (as a surrogate marker for vasopressin) in patients with monosymptomatic nocturnal enuresis, and evaluated whether they are useful for predicting desmopressin treatment outcome.. The study included 32 children 6 to 11 years old with monosymptomatic nocturnal enuresis and nocturnal polyuria. Exclusion criteria were daytime urinary symptoms and underlying diseases causing nocturnal enuresis. Subjects were treated with 120 μg or 240 μg desmopressin oral disintegrating tablet and were divided into responders (at 120 or 240 μg) and nonresponders (at 240 μg). Day/night ratios of plasma copeptin and urinary aquaporin 2 were measured during desmopressin treatment.. There was no significant difference in baseline day/night ratio of urinary aquaporin 2 between desmopressin responders and nonresponders. After 8 weeks of treatment there was a significant correlation between day/night ratio of aquaporin 2 and percentage of wet nights. In responders (but not nonresponders) there was a significant difference in the change in aquaporin 2 day/night ratio from before treatment to complete remission (p = 0.0004). For plasma copeptin the baseline day/night ratio for responders at 120 μg was significantly lower than in the 240 μg nonresponder group (p = 0.02).. Urinary aquaporin 2 appears to be a biomarker of desmopressin treatment effectiveness during therapy, while plasma copeptin levels before treatment are predictive of desmopressin response.

Topics: Antidiuretic Agents; Aquaporin 2; Biomarkers, Pharmacological; Child; Deamino Arginine Vasopressin; Female; Glycopeptides; Humans; Male; Nocturnal Enuresis; Predictive Value of Tests; Prospective Studies; Recurrence; Retrospective Studies; Treatment Outcome

Nocturnal enuresis (NE) is a common pediatric developmental disorder. Desmopressin is frequently used for NE and is an evidence-based therapy. Suoquan capsule is a Chinese medicine commonly used for treating NE in children but is poorly understood by most scholars.. A total of 369 children with NE were randomized to receive either suoquan, desmopressin plus suoquan, desmopressin, or behavioral intervention for 2 months, and the response rates evaluated. Subsequently, the viable demographic factors that could lead to success were investigated on logistic regression analysis. Moreover, after 3 months of follow up, the relapse rate was investigated.. The complete response (CR) rate in the desmopressin plus suoquan group (37.5%) was higher than that in the behavioral intervention group (6.3%, P < 0.007). The desmopressin group had a lower CR rate (22.5%) and a higher non-response rate (25.0%) than the desmopressin plus suoquan group (non-response rate, 21.9%; P > 0.007). The relapse rate in the desmopressin group was significantly higher than that in the desmopressin plus suoquan group (72.2% vs. 30.6%, P < 0.007). On Multivariate analysis, treatment group, NE frequency, and age were independent predictors of CR at 2 months (P < 0.05).. Combined traditional Chinese and Western treatment in children with NE is effective and has a low relapse rate. NE frequency, treatment method, and age are important predictive factors for CR after treatment.

Topics: Adolescent; Antidiuretic Agents; Behavior Therapy; Child; Child, Preschool; Deamino Arginine Vasopressin; Drug Therapy, Combination; Female; Humans; Male; Medicine, Chinese Traditional; Nocturnal Enuresis; Treatment Outcome

Nocturnal enuresis (NE) is intermittent involuntary voiding during sleep in a child aged 5 years or more. The study was conducted to compare the effect of using laser acupuncture and medication for the treatment of children with nocturnal enuresis (NE) and evaluation of urodynamic parameter after treatment. A randomized study included 45 children ranged from 5 to 15 years presenting with NE. They were randomized into three equal groups-group A, managed with desmopressin acetate; group B, managed with laser acupuncture; and group C, managed with a combination of laser acupuncture and desmopressin-all groups received behavioral therapy. The children were evaluated before and after 3 months of the study to record the efficacy of therapy, side effects and bladder capacity, and 3 months of follow-up after cessation of treatment by bladder diary. A statistically significant higher cure rate was reported in group B patients (73.3 %), while in groups A and C, improvement was reported in 20.0 and 13.3 %, respectively (p value = 0.002). Laser acupuncture is noninvasive, painless tool, with no side effects and lower recurrence rate which can be considered as an alternative therapy for patients with NE.

Topics: Acupuncture Therapy; Adolescent; Child; Child, Preschool; Deamino Arginine Vasopressin; Female; Humans; Lasers; Male; Nocturnal Enuresis; Recurrence; Urinary Bladder

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 (0.4 mg) and indomethacin (50 mg) or desmopressin and placebo at bedtime. Home recordings at baseline and for the final 2 weeks 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 ± 14 ml to 258 ± 13 ml, 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.

Topics: Adolescent; Anti-Inflammatory Agents, Non-Steroidal; Child; Cross-Over Studies; Deamino Arginine Vasopressin; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Indomethacin; Male; Nocturnal Enuresis; Polyuria; Renal Agents; Urodynamics

Few studies manage patients with isolated monosymptomatic enuresis (MNE) with multidisciplinary evaluation and pre- and long-term post-intervention monitoring.. This was a prospective study of MNE patients, aged 6-16 years, diagnosed by multidisciplinary assessment. Of the 140 initial applicants (58.6%) with MNE, 82 were included in the study and randomized for therapeutic intervention in three treatment groups, namely: alarm, desmopressin and alarm + desmopressin. Therapeutic response was evaluated 12 months after treatment withdrawal.. Of the 82 patients [mean age 9.5 (SD ± 2.6) years, n = 62 males (75.6%)], 91.1% had a family history of nocturnal enuresis (NE) in first-/second-degree relatives, 81.7% had constipation and 40.7% had mild-to-moderate apnea. Prior to randomization, management of constipation and urotherapy led to remission in seven of the 82 patients; 75 patients were randomized to intervention. There were 14/75 (18.7%) dropouts during the intervention, especially in the alarm group (p = 0.00). Initial complete/partial response was achieved in 56.6% of the alarm group, 70% of the desmopressin group and 64% in the combined group (p = 0.26). Continued success occurred in 70% of the alarm group, 84.2% of the desmopressin group and 100% of the combined group (p = 0.21). Recurrence occurred in 3/20 (15%) patients in the alarm group and 1/19 (5.2 %) patients of the desmopressin group. Post-intervention Child Behavior Checklist (CBCL) and PedsQL 4.0 scores showed significant improvement.. The three therapeutic modalities were effective in managing MNE with low relapse rates; the alarm group showed the highest dropout rate. Therapeutic success was associated with improvement of behavioral problems and quality of life scores.

Topics: Adolescent; Child; Child Behavior; Child, Preschool; Clinical Alarms; Combined Modality Therapy; Constipation; Deamino Arginine Vasopressin; Disease Management; Female; Humans; Male; Nocturnal Enuresis; Patient Care Team; Patient Dropouts; Prospective Studies; Quality of Life; Recurrence; Renal Agents

Desmopressin is used for treatment of nocturnal enuresis in children. In this study, we investigated the pharmacokinetics of two formulations-a tablet and a lyophilisate-in both fasted and fed children.. Previously published data from two studies (one in 22 children aged 6-16 years, and the other in 25 children aged 6-13 years) were analyzed using population pharmacokinetic modeling. A one-compartment model with first-order absorption was fitted to the data. Covariates were selected using a forward selection procedure. The final model was evaluated, and sensitivity analysis was performed to improve future sampling designs. Simulations were subsequently performed to further explore the relative bioavailability of both formulations and the food effect.. The final model described the plasma desmopressin concentrations adequately. The formulation and the fed state were included as covariates on the relative bioavailability. The lyophilisate was, on average, 32.1 % more available than the tablet, and fasted children exhibited an average increase in the relative bioavailability of 101 % in comparison with fed children. Body weight was included as a covariate on distribution volume, using a power function with an exponent of 0.402. Simulations suggested that both the formulation and the food effect were clinically relevant.. Bioequivalence data on two formulations of the same drug in adults cannot be readily extrapolated to children. This was the first study in children suggesting that the two desmopressin formulations are not bioequivalent in children at the currently approved dose levels. Furthermore, the effect of food intake was found to be clinically relevant. Sampling times for a future study were suggested. This sampling design should result in more informative data and consequently generate a more robust model.

Topics: Administration, Oral; Adolescent; Antidiuretic Agents; Biological Availability; Body Weight; Chemistry, Pharmaceutical; Child; Cross-Over Studies; Deamino Arginine Vasopressin; Drug Compounding; Fasting; Female; Food; Humans; Male; Models, Biological; Models, Theoretical; Nocturnal Enuresis; Predictive Value of Tests; Tablets; Therapeutic Equivalency

A significant minority of children with enuresis do not respond to either desmopressin or the enuresis alarm. Anticholinergics have not proven as successful as expected. The fourth evidence-based treatment, the tricyclic antidepressant imipramine, is cardiotoxic when overdosed, which has led to diminished use.. The aim was to determine whether there is a role for the noradrenergic antidepressant reboxetine, as monotherapy or combined with desmopressin, in the treatment of enuresis in children who have not responded to standard therapy, and whether there are side effects involved. We also sought prognostic factors in anamnestic data and in the voiding chart.. The study was a randomized placebo-controlled study with a double-blind cross-over design, in which all patients underwent treatment during three 4-week periods, one with reboxetine 4 mg and placebo, one with reboxetine 4 mg and desmopressin, and one with double placebo treatment. The proportion of wet nights out of 14 was compared before treatment and during the last 2 weeks of each treatment period.. Eighteen patients were included. The reduction of wet nights was much better with either reboxetine in monotherapy or in combination with desmopressin than during the placebo period (p = 0.002) (Figure). However, only one patient achieved complete dryness, this during monotherapy. There were three intermediate responders to monotherapy and five to combination treatment. With reboxetine in monotherapy, six children experienced negative side effects compared with three with combination therapy, and two with placebo. All of these side effects were mild and reversible. Only one patient chose to cease treatment because of side effects. No prognostic factors were found in either the case history or in voiding chart data.. The present study, the first placebo-controlled trial, confirms that reboxetine is an evidence-based alternative to cardiotoxic antidepressant treatment in therapy-resistant enuresis. The fact that few patients achieved complete dryness may be due to the low dosage used. In our clinical practice we increase the dose to 8 mg when dryness is not achieved with the lower dose. Our experience is that this leaves more children with full response, but the evidence of this has yet to be shown.. Reboxetine seems to be an alternative in the treatment of enuretic children who have not responded to standard treatment.

Topics: Adolescent; Antidiuretic Agents; Child; Cross-Over Studies; Deamino Arginine Vasopressin; Double-Blind Method; Drug Resistance; Drug Therapy, Combination; Female; Humans; Male; Morpholines; Nocturnal Enuresis; Reboxetine; Young Adult

We compared the long-term success of desmopressin sublingual lyophilisate formulation and enuretic alarm therapy in children with primary monosymptomatic nocturnal enuresis, and determined predictive factors for treatment success.. A total of 142 children with primary monosymptomatic nocturnal enuresis were randomized to receive treatment consisting of desmopressin or enuretic alarm for 6 months. Treatment compliance and response were reviewed monthly in each patient using a 30-day bed-wetting diary. Outcomes were assessed according to International Children's Continence Society criteria, and success rates at 6 and 12 months were compared for desmopressin and enuretic alarm. Additional intention to treat analyses were performed, considering cases with missing data as failures. Possible demographic factors predicting success were investigated by logistic regression analysis.. Overall 4 children (5.2%) in the desmopressin group and 20 (30.7%) in the enuretic alarm group withdrew after randomization. Based on patients who completed 6 months of treatment, success (more than 90% reduction in wet nights per month) was achieved in 76.8% and 61.8% of children in the desmopressin and enuretic alarm groups, respectively. At 12 months 77.8% of those receiving desmopressin and 75% of those treated with enuretic alarm had success. However, long-term success rate was significantly higher with desmopressin (68.8% vs 46.2%) if intention to treat population was considered. Multivariate analysis revealed treatment group, severity of enuresis and monthly income as independent predictors of cure at 6 months.. In compliant patients desmopressin lyophilisate and enuretic alarm provided equivalent success at the end of treatment and after extended followup. Alarm therapy had a high rate of early withdrawal from therapy and consequently lower rates of success on intention to treat analyses. Severe enuresis (more than 5 wet nights weekly) is an important predictive factor for cure after first-line treatment.

Topics: Adolescent; Antidiuretic Agents; Child; Clinical Alarms; Deamino Arginine Vasopressin; Female; Freeze Drying; Humans; Male; Nocturnal Enuresis; Prognosis; Prospective Studies; Time Factors; Treatment Outcome

Although desmopressin therapy is effective in treating polyuric monosymptomatic nocturnal enuresis (MNE), the relatively high rates of recurrence are problematic. To date, the treatment protocol on the discontinuation of oral desmopressin melt (ODM) tablet, MinirinMelt, has not been established. We tested two protocols of tapering ODM when the patients achieved full response on ODM, and compared the treatment outcomes.. One hundred and fifty-seven polyuric MNE children were newly treated with ODM at the authors' outpatient clinics (Juntendo Nerima Hospital and Musashi-Murayama Hospital). When the patients did not respond to the 8 week ODM therapy, we added another options such as alarm, anti-cholinergics, and imipramine (92 patients; 58.6%). Sixty-five patients (41.4%) achieved full response on ODM alone, and 49 of them accepted gradual tapering of ODM: group B (n = 25), 240 μg ODM per day → 120 μg ODM per day → 120 μg ODM per alternate day → cessation; and group C (n = 24), 240 μg ODM per day → 120 μg ODM per day → 60 μg ODM per day → 60 μg ODM per alternate day → cessation.. Fourteen patients in group B (56%) and four in group C (17%) had relapses of enuresis after the discontinuation of ODM (P = 0.026).. Gradual tapering of ODM therapy in MNE patients leads to better outcome.

Topics: Adolescent; Antidiuretic Agents; Child; Deamino Arginine Vasopressin; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Nocturnal Enuresis; Outpatients; Recurrence; Retrospective Studies; Treatment Outcome; Urination

Many recent treatment guidelines have advocated the importance of a full noninvasive medical evaluation. To individualize treatment, special emphasis must be put on recording of the maximum voided volume (MVV) and nocturnal diuresis in a diary or frequency/volume chart.. The aim of this study was to identify any possible predictive factors to desmopressin response.. This study is a re-analysis of a prospective, open-label, multinational, phase-IV study evaluating ≤6 months of treatment with desmopressin tablets for children with primary nocturnal enuresis. The children were enrolled between April 2002 and December 2004 from 86 centers in four countries: UK, Canada, Germany and France. A total of 936 children were screened; 744 children aged 5-15 years participated in the study. Of these, 471 children completed the study with 6 months follow-up and recording in a frequency/volume chart. All children experienced six or more wet nights during the 14-day screening period. Exclusion criteria were: organic pathology, treatment for enuresis within the past year, previous treatment for enuresis for >4 weeks, diurnal symptoms, renal or central diabetes insipidus and the use of systemic antibiotics or other drugs known to affect desmopressin activity. The predictive value of number of wet nights a week, fluid intake, daytime voiding frequency and diuresis was investigated by performing a multinomial logistic regression.. Of the demographic variables, age was the only significant predictor for response to desmopressin. Controlling for age, the significant predictive variables were: number of wet nights a week, average voided volume daytime, maximum voided volume daytime, total daytime diuresis, nocturnal diuresis (see Figure), maximum voided volume 24 h and total 24 h diuresis. More than 80% of the children had no nocturnal polyuria and a low maximum voided volume.. Performing a secondary analysis is a limitation because the original study was not designed for that. A new prospective study is ethically hardly defendable for children if data are available from previous literature [1]; therefore, a re-analysis was the appropriate choice. The study confirms the predictive value of age, number of wet nights a week and nocturnal diuresis [1,2].. The study demonstrates that desmopressin response rates are higher in children with greater age, limited number of wet nights a week and nocturnal polyuria. Only a minority of a primary nocturnal enuresis population, based on history alone, had nocturnal polyuria. The majority had a low maximum voided volume. The results clearly stress the importance of a frequency/volume chart for individualizing therapy to the characteristics, thereby resulting in elevated success rates. Registration number of clinical trial: Clinical Trials.gov NCT00245479.

Topics: Administration, Oral; Adolescent; Antidiuretic Agents; Child; Child, Preschool; Deamino Arginine Vasopressin; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Male; Nocturnal Enuresis; Prospective Studies; Time Factors; Treatment Outcome; Urination

The higher sensitivity to desmopressin (dDAVP) found in women and older patients with nocturnal polyuria (NP) has partially been unraveled, leading to adaptation of the dosage based on gender. However, besides age and gender, other factors might play a role in differences in sensitivity and side effects. The aim of this study is to design a pharmacokinetic/pharmacodynamic (PD) assay to identify appropriate treatment for different groups of patients, primarily dependent on differences in age and gender.. This interventional pilot study was carried out in Ghent University Hospital, Belgium, between 2011 and 2013. Patients with NP were subjected to a water load test (15 mL/kg), as well as an administration of 120 µg dDAVP oral disintegrating tablet (ODT) followed by blood analysis to determine plasma dDAVP levels and urine analysis for diuresis rate, osmolality, free water clearance and sodium clearance.. Six female and six male patients were included (range 30-89 years old; mean age 69 years; SD 18). Three groups based on plasma dDAVP levels were found: (1) high (only women), (2) intermediate (only men) and (3) low plasma levels. For the nighttime samples (3-12 h after intake) men presented with significantly higher variation in PD response, whereas 12-15 h after dDAVP ODT intake women presented with a less predictable outcome, although all patients but one (female) have a prolonged PD effect.. This study suggests the need for individualized dose titration rather than fixed dose regimens in NP patients with bothersome symptoms. Gender, body weight and results of nocturnal free water and sodium clearance need to be taken into account for more accurate individualized treatment to result in high response rates and low side effects.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Antidiuretic Agents; Belgium; Deamino Arginine Vasopressin; Female; Humans; Male; Middle Aged; Nocturia; Nocturnal Enuresis; Pilot Projects; Sex Factors; Tablets

To assess the effect of oral desmopressin on nocturia and nocturnal enuresis in patients after orthotopic neobladder reconstruction.. Of 55 patients who underwent radical cystectomy and orthotopic neobladder reconstruction at our medical centre in the period 2004-2011, 34 patients were deemed eligible for the present study. Inclusion criteria were estimated glomerular filtration rate >50 mL/min/1.73 m(2) , normal baseline sodium serum level, intact daytime urinary continence, and any degree of nocturia or nocturnal enuresis. Patients were treated daily with oral desmopressin 0.1 mg at bedtime for 30 days and completed the Nocturia, Nocturnal Enuresis and Sleep Interruption Questionnaire at trial enrollment and closure. Sodium serum levels were monitored throughout.. Three patients withdrew from the trial because of headaches or anxiety. The mean (sd) number of nocturnal voids decreased from 2.5 (1.4)/night at baseline to 1.5 (1.3)/night at trial closure (P = 0.015). The number of patients with one or no episodes of nocturnal enuresis per week increased from six to 12 (19 to 39%; P = 0.065). Thirteen patients (42%) reported an increase of a minimum 1-2 h of sleep until the first nocturnal void; all of them asked to continue the drug. No significant adverse events or changes in sodium level were observed.. Bedtime treatment with low-dose oral desmopressin appears to decrease episodes of nocturia and nocturnal enuresis effectively and safely in ∼50% of the patients with neobladder, allowing longer undisrupted sleep time and improved quality of life. Further investigation is warranted to determine if higher doses would result in a more meaningful clinical response.

Topics: Aged; Antidiuretic Agents; Cystectomy; Deamino Arginine Vasopressin; Female; Humans; Male; Middle Aged; Nocturia; Nocturnal Enuresis; Quality of Life; Surveys and Questionnaires; Urinary Diversion

Monosymptomatic nocturnal enuresis (MNE) is a common sociomedical problem affecting children that may persist until adulthood despite various lines of therapy. The aim of this study was to assess the efficacy of combined laser acupuncture and desmopressin in managing patients with resistant MNE, compared with their efficacy when used as monotherapy.. The study included 186 patients with a mean age of 15.7 years (range 10-21 years) presenting with persistent MNE. All patients were evaluated clinically and investigated with urine analysis, plain X-ray of the urinary tract and abdominal ultrasonography. They were randomized into three equal groups based on the line of management: group A, managed with laser acupuncture alone; group B, managed with desmopressin alone; and group C, managed with a combination of laser acupuncture and desmopressin, with a treatment course of 3 months and follow-up period of 6 months to record the efficacy of therapy, side-effects and bladder capacity.. A statistically significant higher cure rate was reported in group C patients, being reported in 33, 35 and 46 patients in groups A, B and C, respectively. Improvement was reported in 18, 17 and 13 cases in groups A, B and C, respectively, but the difference was not statistically significant. Bladder capacity significantly increased only in patients receiving acupuncture (groups A and C).. Combined laser acupuncture and desmopressin is a promising and valid option to manage resistant cases of MNE.

Topics: Acupuncture Therapy; Adolescent; Antidiuretic Agents; Child; Combined Modality Therapy; Deamino Arginine Vasopressin; Female; Humans; Lasers, Semiconductor; Male; Nocturnal Enuresis; Treatment Outcome; Young Adult

This pre-specified sub-study of the desmopressin response in primary nocturnal enuresis study (DRIP study) evaluates the safety profile of the oral desmopressin tablet in children with primary nocturnal enuresis. Endpoints are adverse events and change in body mass index.. The DRIP study was an open-label, intention-to-treat, phase IV, multi-national study. Overall, 936 patients were screened and 744 children aged 5-15 years with previously untreated primary nocturnal enuresis were eligible to receive the study medication desmopressin once daily as an oral tablet formulation. At each visit, adverse events were questioned and observed signs or symptoms were recorded.. Overall, 222 (30%) patients experienced 404 treatment-emergent adverse events. The proportion of patients experiencing treatment-emergent adverse events was similar regardless of patient gender or age. Most treatment-emergent adverse events were experienced in three system organ classes: gastrointestinal disorders; infections and infestations; and respiratory, thoracic and mediastinal disorders and were considered unrelated to the study drug. There was a slight increase in body mass index from screening levels during the study, however, clinically not significant.. Desmopressin tablet treatment is well tolerated in children with primary nocturnal enuresis, regardless of patient gender or age.. The desmopressin response in primary nocturnal enuresis study (DRIP- study) was funded by Ferring.

Topics: Administration, Oral; Adolescent; Antidiuretic Agents; Body Mass Index; Child; Child, Preschool; Deamino Arginine Vasopressin; Female; Humans; Male; Nocturnal Enuresis; Prospective Studies; Symptom Assessment; Tablets; Treatment Outcome

Primary nocturnal enuresis is a prevalent childhood condition that can persist into adulthood. Desmopressin is an antidiuretic available as orally disintegrating lyophilisate (melt) or solid tablet. Recent findings suggesting different food interactions and clinical characteristics, including compliance, between desmopressin melt and tablet motivated a post hoc analysis of a previously reported randomised, crossover study. The efficacy of desmopressin melt compared with tablet was evaluated using the International Children's Continence Society (ICCS) responder definitions. Compliance was further analysed using detailed criteria, and the association between efficacy and compliance was examined. In total, 221 patients aged 5-15 years, already receiving desmopressin tablets were randomised to the treatment sequence melt (120/240 μg)/tablet (0.2/0.4 mg) or tablet/melt in two consecutive 3-week periods. The probability of being a responder (partial or full) during either period was significantly more likely with desmopressin melt compared with tablet (odds ratio, 2.0; confidence intervals, 1.07-3.73; p = 0.03). There was no period effect on compliance in the tablet/melt sequence and no difference in the number of completely compliant patients in each formulation group; however, more patients were >75 % compliant in period 1 compared with period 2 in the melt/tablet sequence. Increased compliance was associated with greater reductions in the number of wet nights for both formulations.. Desmopressin melt, compared with tablet, improves the probability of being a responder. Switching from tablet to melt formulation increased patient compliance. Increased compliance was associated with increased efficacy. Switching to desmopressin melt may benefit patients with suboptimal responses to desmopressin tablet.

Topics: Administration, Oral; Adolescent; Antidiuretic Agents; Child; Cross-Over Studies; Deamino Arginine Vasopressin; Drug Administration Schedule; Female; Freeze Drying; Humans; Logistic Models; Male; Medication Adherence; Nocturnal Enuresis; Odds Ratio; Tablets; Treatment Outcome

To assess the efficacy of desmopressin plus oxybutynin and compare two starting dosages of desmopressin (120 and 240 µg) in a randomized, double-blinded, placebo-controlled trial for children with monosymptomatic nocturnal enuresis (MNE) resistant to desmopressin. The predictive factors of children with MNE responsive to desmopressin and combination therapy were also evaluated.. Our sample included 206 patients aged between 6 and 13 (mean age 10.6 ± 2.9 years), 117 males. All patients were required to have MNE. The patients were randomly divided into two groups: the first group was given oral melt 120 µg and the second group 240 µg, for 2 weeks. All patients who had experienced failure of treatment with sublingually administered desmopressin alone were given either desmopressin plus 5 mg oxybutynin or desmopressin plus placebo in a randomized, double-blinded trial for 4 weeks. As predictive factors, bladder volume and wall thickness index, nocturnal polyuria and voiding latency were considered.. There was no significant difference between the 120 µg and 240 µg patients in terms of response. The oxybutynin group showed a higher rate of full and partial responses (45% success) compared with the placebo group (17% success), P < 0.01. The responders to combined oxybutynin and desmopressin had significantly lower bladder volume and wall thickness index than the other patients.. Our findings highlight that anticholinergic agents may play an important role for a subset of children with enuresis who have a restricted bladder capacity and thickened bladder wall. Ultrasonography-measured bladder variables can provide useful predictive clues for MNE. Predictive factors can help to differentiate treatment subtypes and guide clinical management in primary nocturnal enuresis.

Topics: Adolescent; Antidiuretic Agents; Child; Deamino Arginine Vasopressin; Double-Blind Method; Female; Humans; Male; Mandelic Acids; Nocturnal Enuresis

Monosymptomatic enuresis (ME) is a common disorder in children with serious social and psychological consequences. Treatment is usually initiated with desamino-arginine vasopressin (dDAVP) and/or alarm therapy as first-line treatment and imipramine as second-line. All treatments have proven efficacy, but are not successful with all patients. Therefore, a differentiation into subgroups according to treatment efficacy would be beneficial.. A group of patients resistant to first-line treatment was treated with imipramine and compared with matched controls successfully treated with dDAVP and/or alarm therapy. Prepulse inhibition (PPI) to acoustic startle reflexes was measured in all patients.. In a group of 23 nonresponders, the median PPI was 72% (range 43-94%) compared with the matched dDAVP/alarm - responders with a median PPI of 26% (range 0-61%) (p < 0.0001). The response rate to imipramine was 87%.. The presented data provide evidence that PPI allows to identify two subgroups of ME. The results offer further insight into (at least) two different pathomechanisms involved in ME: (i) a maturational delay of reflex inhibition with reduced PPI and (ii) a normal PPI, possibly with abnormal sleep patterns, that can be influenced by imipramine.

Topics: Acoustic Stimulation; Adolescent; Adrenergic Uptake Inhibitors; Antidiuretic Agents; Child; Clinical Alarms; Combined Modality Therapy; Deamino Arginine Vasopressin; Female; Humans; Imipramine; Male; Nocturnal Enuresis; Prospective Studies; Reactive Inhibition; Reflex, Startle; Treatment Outcome

To compare the efficacy of long-term primary nocturnal enuresis (PNE) treatment using desmopressin versus enuresis alarm.. A 6-month randomized trial was performed with patients from 29 enuresis clinics: 251 patients ≥ 5 years in age with severe PNE (mean 5.5-5.6 wet nights/week) were randomized to desmopressin (0.2-0.4 mg daily) or alarm. Efficacy was assessed by percentage reduction in mean number of wet nights/week; patients achieving dryness, mean initial duration of sleep and compliance were evaluated. Efficacy analyses were performed using the intent-to-treat population (all patients) and excluding patients who withdrew; 12-month follow-up data were collected.. Data could not be evaluated for the 32% of alarm patients and 7% of desmopressin patients who withdrew early. In intent-to-treat analyses, a similar proportion of patients across groups showed a ≥ 50% reduction in wet nights/week (desmopressin: 37.5%, alarm: 32.2%) and achieved dryness (desmopressin: 32%, alarm: 37%). Compliance was higher with desmopressin: 95-98% of patients took >75% of tablets; 50-78% used alarm >75% of nights. Initial sleep duration was 1.02 h longer at the end of treatment with desmopressin (95% CI: 0.045, 1.99).. Desmopressin and alarm demonstrated comparable efficacy in the treatment of PNE. Withdrawal from the alarm group was high, indicating the importance of considering family motivation before selecting treatment, for optimal outcome.

Topics: Adolescent; Antidiuretic Agents; Child; Child, Preschool; Clinical Alarms; Deamino Arginine Vasopressin; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Male; Nocturnal Enuresis; Patient Compliance; Patient Dropouts; Sleep; Time Factors; Treatment Outcome

To evaluate the efficacy of different modes of combined therapy in children with monosymptomatic nocturnal enuresis (MNE).. A randomized prospective study was performed to compare the order of two types of combined therapy in children with MNE. Group A was treated with primary desmopressin treatment that was combined with alarm treatment after 3 months, while group B was treated with primary alarm treatment that was combined with desmopressin after 3 months.. Within a period of 18 months, 43 previously untreated children fulfilled the inclusion criteria. Thirteen children achieved dryness after initial monotherapy or discontinued the study. Group A consisted of 16 children and group B of 14 children. After the standardized treatment course of 6 months, 11/16 children in group A and 11/14 children in group B became dry (<3 wet nights/month). Altogether, 22/30 (73%) children were dry after combined treatment, consisting of 12/18 boys and 10/12 girls. Of the children with a normal maximum voided volume, 79% (19/24) achieved dryness, whereas only three of six children with small maximum voided volumes became dry. In all, 13/19 (68%) children with nocturnal polyuria and nine of 11 without nocturnal polyuria became dry. Only one child relapsed (group A).. Combined therapy proved effective in children with MNE after 6 months, with no statistically significant differences between the two different orders of treatment.

Topics: Adolescent; Antidiuretic Agents; Behavior Therapy; Child; Child, Preschool; Combined Modality Therapy; Deamino Arginine Vasopressin; Female; Humans; Male; Nocturnal Enuresis; Prospective Studies

To evaluate the effect of 1-desamino-8-D-Arginine Vasopressin (DDAVP) on sleep architecture and arousal reactions in children with primary monosymptomatic nocturnal enuresis (PME).. A prospective, placebo-controlled, randomized, double-blind, cross-over study was performed on children suffering from bed-wetting. Placebo and DDAVP were given for 7 days each after which an unattended home polysomnography (PSG) was recorded. After lifting the blinding, the PSGs were compared.. A total of 20 children with PME, aged 6-15 years, were enrolled in the study. The number of wet nights decreased significantly with DDAVP treatment. Delta power, distribution of sleep stages, number of arousals, arousal index and the effect of arousals on sleep stages did not differ significantly. Bed-wetting occurred within each sleep stage and did not follow any particular pattern. In most cases, it was preceded by an arousal reaction, but no awakening occurred.. DDAVP has no effect on the sleep architecture of children with PME when analysed by classical PSG, which is determined by collecting the electric activity of cortical neurons. Taking recent research findings into account, this supports the thesis that the disturbances causing PME occur at brain stem level and do not reach consciousness.

Topics: Adolescent; Antidiuretic Agents; Child; Cross-Over Studies; Deamino Arginine Vasopressin; Double-Blind Method; Female; Humans; Male; Nocturnal Enuresis; Placebos; Polysomnography; Prospective Studies; Sleep; Treatment Outcome

To investigate possible differences in the prognosis in children with severe nocturia who received different drug withdrawal schedules.. Ninety-seven children with severe nocturia were randomly assigned to two groups: control (n=47) and observed (n=50). The control group accepted drug withdrawal immediately, while the observed group accepted dose tapering gradually after a 12-week treatment course. The frequency of enuresis was observed three months after complete drug withdrawal.. During the treatment, the frequency of enuresis in all of children from both the control and the observed groups was reduced by over 90%. Forty-six children (92%) from the observed group showed the frequency of enuresis was reduced by over 90%, but 28 children (60%) from the control group (p<0.01) three months after the complete drug withdrawal. There were no significant differences in the adverse effect and the medication compliance between the two groups.. The different schedules of drug withdrawal may lead to different prognosis, and the schedule of gradual drug withdrawal may be superior to the immediate one in children with nocturnal enuresis.

Topics: Adolescent; Child; Deamino Arginine Vasopressin; Drug Administration Schedule; Female; Humans; Male; Nocturnal Enuresis

We compared the efficacy of desmopressin and enuresis alarm as first and second line treatment options for monosymptomatic nocturnal enuresis.. A total of 104 children with monosymptomatic nocturnal enuresis were randomly assigned to either desmopressin (54) or enuresis alarm (50) as first line treatment. Following 12 weeks of first line treatment children with a full response were evaluated for relapse 12 weeks after withdrawal of treatment. Children with partial or no response were switched to the alternative treatment and then evaluated after 12 weeks of crossover treatment. Relapse was defined as more than 1 episode of bedwetting monthly.. Following first line treatment 77.8% of the desmopressin group and 82% of the enuresis alarm group achieved a successful result, including full response in 37% and 50% of the groups, respectively (p=0.433). Of the children with a full response 50% in the desmopressin group and 12% in the enuresis alarm group experienced a relapse when treatment stopped (p=0.005). Following second line crossover treatment 71.4% of the enuresis alarm-desmopressin group and 67.8% of the desmopressin-enuresis alarm group achieved a successful result, including full response in 47.6% and 45.2% of the groups, respectively (p=0.961).. There was no difference between desmopressin and enuresis alarm during treatment for achieving dryness, but the chance of relapse after treatment stopped was higher following desmopressin. Switching to the alternative treatment following partial or no response provided an additional benefit.

Topics: Adolescent; Antidiuretic Agents; Child; Clinical Alarms; Cross-Over Studies; Deamino Arginine Vasopressin; Female; Humans; Male; Nocturnal Enuresis; Prospective Studies

Primary nocturnal enuresis (PNE) is a distressing condition, particularly in severe cases (> or = 3 wet nights/week). A prevalent pathophysiological mechanism, especially in monosymptomatic PNE (PMNE), is commonly believed to be an insufficient increase in night-time release of antidiuretic hormone. Desmopressin, a synthetic analogue of antidiuretic hormone, has been shown to reduce the number of wet nights experienced by PMNE patients in several controlled trials.. This study was performed to evaluate desmopressin treatment in the real-life clinical setting and was a large-scale, 6-month investigation of efficacy and safety in patients with severe PNE. Predictive factors for desmopressin response were also evaluated. A total of 744 children aged 5 years and above from four countries were involved in the study.. At baseline, patients had a median of 6 wet nights/week; at 6 months, 41% of patients had experienced > or = 50% reduction in the mean number of wet nights. Long-term desmopressin treatment was consistently well-tolerated across all ages, with 5% of patients experiencing any treatment-related adverse events. The strength of treatment response was associated with nocturnal diuresis (p < 0.0001) and age (p = 0.0167) in logistic regression analyses. Compliance and dosage were also associated with response and more patients experienced > or = 50% reduction in wet nights after 6 months' treatment than earlier in the study, suggesting the value of persistent treatment.. This study shows that long-term desmopressin treatment in the clinical setting is effective and well-tolerated in PNE patients of 5 years and upwards. Early improvements in bedwetting of any appreciable magnitude may be rewarding, may facilitate compliance and enable good long-term response.

Topics: Adolescent; Antidiuretic Agents; Child; Child, Preschool; Deamino Arginine Vasopressin; Dose-Response Relationship, Drug; Female; Humans; Male; Nocturnal Enuresis; Patient Compliance; Time Factors; Treatment Outcome

Desmopressin (a structural analogue of hormone arginine-vasopressine) is an effective treatment of primary nocturnal enuresis (PNE). A new oral formulation (oral lyophilisate; Minirinmelt has recently been developed. The principal objective of this study was to compare the preference of patients for the oral lyophilisate versus tablet.. This open-label, randomized, cross-over study was undertaken at 26 centres across Europe and included patients with PNE. All were already receiving a stable dose of desmopressin tablets 0,2 or 0,4 mg. Two hundred and fourteen patients aged 6 to 15 years were randomised (1:1) to receive the treatment in the order lyophilisate/tablet (n=108) or tablet/lyophilisate (n=106). Each formulation was taken during 3 weeks.. Of the patients (intention to treat), 55,2% preferred the oral lyophilisate (p=0,16). Patients less than 12 years (n=153) had a preference for the lyophilisate compared to tablets (60,1%; p=0,015). Efficacy was the same for both formulations in terms of mean incidence of bedwetting episodes per week (treatment difference: -0,08; p=0,33). No serious adverse event was reported. The use was considered to be easy for the two forms (p=0,85). Of patients on the lyophilisate, 94,3% had compliance levels of greater or equal to 80%.. The majority of patients preferred the sublingual lyophilisate. This preference was marked in patients less than 12 years on exploratory analysis. The new formulation of desmopressin requires no water intake and retains similar levels of efficacy and safety than the tablet.

Topics: Administration, Sublingual; Adolescent; Antidiuretic Agents; Child; Cross-Over Studies; Deamino Arginine Vasopressin; Female; Humans; Male; Nocturnal Enuresis; Patient Satisfaction; Prospective Studies

To evaluate the response rate of various modalities of therapy in primary nocturnal enuretic children according to the ultrasound bladder volume and wall thickness index (BVWI) measurements.. From February 2006 to November 2007, a total of 31 children, aged 6-12 years old were enrolled in a clinical trial. Based on BVWI they were divided into 3 groups as follows: Group 1 (BVWI <70%) was treated with oral desmopressin and oxybutynin; Group 2 (BVWI 70% to <130%) was treated with oral desmopressin. Group 3 (BVWI >130%) was treated with oral desmopressin accompanied by double-voiding technique and scheduled voiding. All of them were treated for 3 months.. Significant reductions in mean bed-wetting frequency before and after first treatment cycle were observed in all groups (p<0.05). The complete response rate was 70% in Group 1, 25% in Group 2, and 20% in Group 3. Overall, the complete and partial response rate was 9/10 (90%) children in Group 1, 13/16 (81%) in Group 2, and 3/5 (60%) in Group 3. Bedwetting frequency significantly decreased at the first and second treatment cycles in Group 2 (p<0.05) for each pair wise comparison.. The proposed treatment representation according to ultrasound BVWI measurements achieves favorable response rates in children with PNE. We suggest that this treatment should be used to develop the management of enuresis in children.

Topics: Antidiuretic Agents; Child; Clinical Protocols; Combined Modality Therapy; Deamino Arginine Vasopressin; Drug Therapy, Combination; Female; Humans; Male; Mandelic Acids; Muscarinic Antagonists; Nocturnal Enuresis; Organ Size; Ultrasonography; Urinary Bladder

Desmopressin is an approved medical therapy for the treatment of monosymptomatic primary nocturnal enuresis. In cases of limited response to desmopressin, we have added anticholinergic therapy to desmopressin (combination therapy). To evaluate this treatment strategy, we examined the efficacy of combination therapy for primary nocturnal enuresis in desmopressin-nonresponders.. Only patients with primary nocturnal enuresis refractory to the maximal dosage of desmopressin were enrolled. Children with lower urinary tract symptoms or bowel dysfunction were excluded, on the basis of a 3-day, 24-hour, frequency-volume chart and elimination record. Children continued to take desmopressin and were assigned randomly, in a double-blind manner, to receive either extended-release anticholinergic medication or placebo. Patients were reassessed after 1 month of therapy, with a 1-week nocturnal record.. Forty-one desmopressin-nonresponders were enrolled, and 7 patients were excluded because of noncompliance. The treatment groups were equally matched with respect to age, gender, functional bladder capacity, and number of wet nights per week. After 1 month of treatment, there was a significant reduction in the mean number of wet nights in the combination therapy group, compared with the placebo group. With a generalized estimating equation approach, there was a significant 66% decrease in the risk of a wet episode, compared with the placebo group.. This study represents the first prospective, placebo-controlled trial examining the effect of desmopressin in combination with long-acting, anticholinergic, bladder-relaxing therapy for monosymptomatic primary nocturnal enuresis.

Topics: Adolescent; Antidiuretic Agents; Benzhydryl Compounds; Capsules; Child; Cresols; Deamino Arginine Vasopressin; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Muscarinic Antagonists; Nocturnal Enuresis; Phenylpropanolamine; Prospective Studies; Tolterodine Tartrate; Treatment Failure; Treatment Outcome

The aim of this trial was to compare the safety and efficacy of homotoxicological remedies versus placebo and versus desmopressin (dDAVP) in the treatment of monosymptomatic nocturnal enuresis (MNE). We conducted a randomised, double-blind, double-dummy, controlled trial in which 151 children with MNE were randomly assigned to receive oral homotoxicological remedies (n = 50), dDAVP (n = 50) or placebo (n = 51). The primary outcomes were: the reduction of wet nights per week after 3 months of therapy; the evaluation of the numbers and percentages of non-responders and responders; the number of children relapsing after initial response and the number of children attaining 14 consecutive dry nights during the treatment. The secondary outcome was the detection of adverse effects. Baseline clinical characteristics were similar in the three groups of patients. After the 3 months of therapy there was a significant difference between the three groups (P < 0.001) in the mean number of wet nights per week. The daily dose of dDAVP produced a statistically significant decrease (62.9%) in wet nights compared to placebo (2.4%) (P < 0.001) and compared to homotoxicological remedies (30.0%) (P < 0.001). There was a significant decrease in wet nights among the group treated with homotoxicological medications if compared with placebo (P < 0.001). The full response achieved with homotoxicological remedies (20%) was superior if compared with placebo (0%) (P < 0.001). Homotoxicology was superior to placebo (P < 0.001) with regard to the number of children attaining 14 consecutive dry nights during treatment. Our study demonstrates that homotoxicology is safe and effective when compared with placebo, even if it is significantly less effective than dDAVP in this clinical condition.

Topics: Administration, Oral; Adolescent; Antidiuretic Agents; Child; Deamino Arginine Vasopressin; Double-Blind Method; Female; Homeopathy; Humans; Male; Nocturnal Enuresis; Placebos; Treatment Outcome; Urination

The purpose was to evaluate the efficacy of the addition of short-term desmopressin to enuretic alarm in patients with primary monosymptomatic nocturnal enuresis (PMNE).. A total of 58 [corrected] children with PMNE were included in this study. The patients were randomized into two groups. In group 1 (n=30), the patients were given 6 weeks of additional oral desmopressin to 12 weeks of enuretic alarm therapy, as a single dose of 0.2 mg at the first 3 weeks and 0.4 mg at the following 3 weeks. In group 2 (n=28), the patients were given 12 weeks of enuretic alarm therapy alone. According to the number of wet nights after 12 weeks of treatment, the patients were defined as complete responders (dry or more than 75% reduction in wet nights), partial responders (50 to 75% reduction) and non-responders (less than 50% reduction). Relapse was defined as the reappearance of >1 wet night per week for complete responders and >50% increase in pre-treatment wetting frequency for partial responders, and all these patients were called relapsers.. The mean number of wet nights after 3 and 6 weeks treatment was significantly lower in group 1 compared to group 2. However, there was no significant difference between the groups regarding the mean number of wet nights after 12 and 24 weeks of treatment. There was no significant difference between the groups regarding the number of responders, partial responders, non-responders and relapsers. In the group with additional desmopressin therapy given, the number of patients who abandoned therapy was lower than the alarm therapy alone group, but it was not statistically significant.. Our data showed that the addition of short-term desmopressin to alarm therapy was more effective only in the period when it was given, and it did not change the response to alarm therapy in the long term.

Topics: Administration, Oral; Adolescent; Antidiuretic Agents; Behavior Therapy; Chi-Square Distribution; Child; Combined Modality Therapy; Deamino Arginine Vasopressin; Female; Follow-Up Studies; Humans; Male; Nocturnal Enuresis; Treatment Outcome

Enuresis nocturna is a common problem. Numerous etiologic factors have been investigated, and various theories have been proposed. The objectives of our study were to establish the differences in the sleep quality of nocturnal enuretic patients from that of healthy voluntary subjects, and the changes after treatment with desmopressin acetate (DDAVP), among primary school children. The study comprised 19 children with primary nocturnal enuresis and 32 healthy children in the control group. Subjective assessment of sleep was determined with the Pittsburgh Sleep Quality Index (PSQI) questionnaire. PSQI scores for each patient and control subject were determined before the study was started and after a month time interval. The sleep quality of the nocturnal enuretic children was poor. We found lower scores after a month's treatment with DDAVP, and significant differences in two dimensions in the patient group: 'subjective sleep quality' and 'sleep disturbances'. When we asked the patients' group what caused the sleep disturbance, they replied 'the fear or the anxiety of bedwetting during sleep'. This anxiety or fear seemed to be a factor that probably affected their sleep quality. So, active treatment (medical or behavioral) should be started as soon as the child is ready to receive it or when the enuretic child wants to be dry when asleep.

Topics: Antidiuretic Agents; Anxiety; Child; Deamino Arginine Vasopressin; Fear; Female; Humans; Male; Nocturnal Enuresis; Sleep; Sleep Arousal Disorders; Surveys and Questionnaires; Treatment Outcome

The aim of this study is to evaluate the use of desmopressin acetate (DDAVP) in the management of nocturnal enuresis in patients with spinal cord injury (SCI), as well as arginine vasopressin (AVP) daily production, urine output, urine osmolarity and clean intermittent catheterization (CIC) before and after the use of desmopressin.. We studied 11 patients with SCI (7 men 4 women). All patients attended a rehabilitation program and used a wheelchair for locomotion. To improve bladder function and achieve socially acceptable continence all patients were placed on a regimen of anticholinergic drugs (oxybutynin 5 mg, 1x3 daily), evening antibiotic prophylaxis and CIC. The subjects were also on night CIC in order to avoid nocturnal incontinence. DDAVP was given intranasally (20 mg before bedtime) in association with other standard therapy. Urine samples were collected under sterile conditions from all patients at 6:00 a.m. and 6:00 p.m. Urine volume was measured and the amount of urine per hour was calculated. Blood samples were also taken to measure serum AVP, urea, creatinine and serum electrolyte.. Our data suggest that nocturnal polyuria in SCI patients occurs due to a lack of diurnal variation of antidiuretic hormone (ADH) secretion. The use of desmopressin produced a statistically significant increase in urine production rate during the day (56.2 vs 81.2 mL/h, P<0.001) and a decrease in nocturnal urine production (59.2 vs 27.7 mL/h, P<0.001). Desmopressin treatment reflects also on urine osmolarity, which did not change during the day (496 vs 489 mOsm/mL, P>0.5) but showed a significant increase during the night (385 vs 862 mOsm/mL, P<0.001). There was a significant decrease in night CIC. No serious adverse effects were observed.. Our results suggest that desmopressin administration is an beneficial treating option for patients with SCI when fluid restriction and other preventive measures are not able to control abnormal nocturnal polyuria.

Topics: Adult; Antidiuretic Agents; Arginine Vasopressin; Deamino Arginine Vasopressin; Female; Humans; Male; Nocturnal Enuresis; Osmolar Concentration; Spinal Cord Injuries; Treatment Outcome; Urinary Catheterization; Urine

We aimed at comparing the success rates of primary enuretic alarm therapy with those of secondary alarm therapy after failed pharmacotherapy in the treatment of monosymptomatic nocturnal enuresis (MNE).. We randomly applied enuretic alarm therapy in 35 MNE patients (group 1) and desmopressin therapy in 49 MNE patients (group 2). The success and rebound rates after 3 and 6 months were determined. We also applied enuretic alarm therapy as a secondary treatment in 19 group 2 patients with complete rebound after 6 months (group 3). The success rates of patients who have received primary and secondary enuretic alarm therapy were compared.. The success rates for groups 1 and 2 were 82.65 and 81.63%, respectively (p = 0.885), at 3 months and 54.28 and 26.53%, respectively (p = 0.007), at 6 months. The success rates in group 3 were 84.21 and 52.63%, respectively, at 3 and 6 months. When these success rates were compared between groups 1 and 3, no statistically significant difference was found (p = 1.000).. Prior pharmacotherapy did not increase success rates of alarm therapy in our MNE patients.

Topics: Adolescent; Antidiuretic Agents; Child; Deamino Arginine Vasopressin; Female; Humans; Male; Nocturnal Enuresis; Therapeutics; Treatment Failure

Applying three treatment methods for enuresis in children with primary nocturnal enuresis (PNE) in a randomized controlled clinical trial (RCT) to compare the curative effects and characteristics of the three methods.. If the parents and children consented to accept the treatment for 4 months and to keep on follow-up, the children diagnosed as primary nocturnal enuresis in the department of developmental and behavioral pediatrics in Shanghai Children's Medical Center from April 2003 to August 2004 were randomized into three groups: 52 children were in physio-psychological treatment group and were treated by utilizing the conditioning training role of alarm and other psychological and behavioral training programs; 46 children were in drug treatment group and were treated by taking DDAVP tablets orally; 40 children were in combined treatment group who were treated by applying the former two methods simultaneously. If the parents and children did not accept treatment, they were enrolled into the control group and were followed-up. Then, the curative effects of the four groups were compared statistically when the 4-month treatment was over and compared again 3 months later.. Applying the physio-psychological treatment for 4 months, the short-term cure rate of children with enuresis was 75.0%. Three months after the end of the treatment, the long-term cure rate was 71.2%. As for drug treatment group, the short-term cure rate of children with enuresis was 47.8%, the long-term cure rate was 28.3%; As for combined treatment group, the short-term cure rate of children with enuresis was 85.0%, the long-term cure rate was 80.0%. The short-term and long-term curative effects of physio-psychological treatment group and combined treatment group were better than that of drug treatment group (P < 0.01). However, the short-term and long-term curative effects were not significantly different between physio-psychological treatment and combined treatment group (P > 0.05). Physio-psychological treatment exerts effects slowly, but showed sustained curative effects. While Drug treatment exerts effects rapidly, but the relapse rate was very high after discontinuation of the medication.. Physio-psychological treatment and drug treatment are currently generally recognized the best ways to treat enuresis, both of them are suitable for Chinese enuresis children, both of them showed good curative effects. Physio-psychological treatment develops children's ability to control nocturnal micturition, its curative effects were better than that of the drug treatment whilst its relapse rate is lower as compared to drug treatment. So, physio-psychological treatment is more suitable for widespread use to treat PNE in China.

Topics: Adolescent; Antidiuretic Agents; Behavior Therapy; Child; Child, Preschool; Combined Modality Therapy; Deamino Arginine Vasopressin; Female; Humans; Male; Nocturnal Enuresis; Treatment Outcome

Desmopressin is a useful treatment for primary nocturnal enuresis (PNE), a common childhood condition that can persist into adolescence. This open-label, randomised, cross-over study evaluated the preference of children and adolescents with PNE for sublingual desmopressin oral lyophilisate (MELT) vs. tablet treatment, and the efficacy, safety, compliance and ease of use associated with each formulation. In total, 221 patients aged 5-15 years who were already receiving desmopressin tablets were randomised 1 : 1 to receive desmopressin treatment in the order MELT/tablet (n = 110) or tablet/MELT (n = 111) for 3 weeks each. Each formulation was administered in bioequivalent doses (0.2/0.4 mg tablets identical with 120/240 microg MELT). Following treatment, patients were questioned regarding treatment preference. Diary card data and 100 mm Visual Analogue Scale scores were also recorded.. Overall, patients preferred the MELT formulation to the tablet (56% vs. 44%; p = 0.112). This preference was age dependent (p = 0.006); patients aged < 12 years had a statistically significant preference for desmopressin MELT (p = 0.0089). Efficacy was similar for both formulations (MELT: 1.88 +/- 1.94 bedwetting episodes/week; tablet: 1.90 +/- 1.85 episodes/week). Ease of use of both formulations was high. Compliance (> or = 80%) was 94.5% for MELT patients vs. 88.9% for the tablet (p = 0.059). No serious/severe adverse events were reported.. There was an overall preference for the MELT, and a statistically significant preference for desmopressin MELT in children aged 5-11 years. Desmopressin MELT had similar levels of efficacy and safety at lower dosing levels than the tablet, and therefore facilitates early initiation of PNE treatment in children aged 5-6 years.

Topics: Administration, Oral; Adolescent; Antidiuretic Agents; Child; Cross-Over Studies; Deamino Arginine Vasopressin; Female; Humans; Male; Nocturnal Enuresis

To evaluate the effect of extracorporeal magnetic innervation (ExMI) therapy in children with refractory monosymptomatic nocturnal enuresis (MNE).. A total of 55 children (34 boys and 21 girls, median age 8.0 years, range 5 to 13) who wetted the bed more than twice per week because of MNE that was refractory to treatment with desmopressin, anticholinergics, and enuretic alarm were assessed prospectively using a voiding diary before and after ExMI, administered once a week for at least 4 weeks with a size-adjusted magnetic chair (each session lasted 20 minutes).. After all sessions of ExMI, the mean frequency of nocturnal enuresis decreased significantly to 2.09 +/- 2.47 in all patients (P = 0.04), and the mean functional bladder capacity increased 1.88 times in all patients (P = 0.00). In total, 63.6% of our patients had a nocturnal enuresis frequency of less than 50% after a mean of 6.62 +/- 4.26 ExMI sessions.. From our results, reduced functional bladder capacity might be the main pathophysiologic cause in children with MNE refractory to established treatment. ExMI might have an acute inhibitory effect in these children with refractory MNE by increasing functional bladder capacity. However, long-term follow-up data and controlled study with a sham-stimulation group are necessary to determine the durability of this new therapy for refractory MNE.

Topics: Adolescent; Child; Child, Preschool; Cholinergic Antagonists; Deamino Arginine Vasopressin; Drug Resistance; Female; Humans; Magnetics; Male; Nocturnal Enuresis; Organ Size; Prospective Studies; Urinary Bladder

There is increasing evidence that a subgroup of patients with monosymptomatic nocturnal enuresis and nocturnal polyuria resistant to desmopressin may have an abnormal circadian rhythm of renal tubular sodium handling. The pathogenesis of this phenomenon remains to be elucidated. If the increased sodium excretion overnight results in desmopressin resistance, decreasing the sodium excretion overnight may result in subsequently better desmopressin response.. We conducted a pilot study of the anti-enuretic and antidiuretic effects of desmopressin combined with 0.5 mg/kg furosemide daily in patients with desmopressin resistant nocturnal polyuria despite dietary sodium and protein restriction. Values were plotted against the reference frame of a desmopressin responsive enuresis group.. Baseline values revealed significantly lower urinary osmolality and higher diuresis rate overnight compared to the reference population (monosymptomatic nocturnal enuresis desmopressin responders). Introduction of desmopressin resulted in normalization of nocturnal urinary osmolality. However, nocturnal polyuria persisted, despite reaching maximal urinary concentration overnight. Although protein and sodium restriction resulted in a significant decrease in urinary osmolality and diuresis rate, the difference was not clinically important enough to reach normal values or to achieve continence. Furosemide in the morning resulted in a significant increase in diuresis and osmotic and sodium excretion during the day, and decreased nighttime diuresis and osmotic excretion. In 9 of 12 patients the nocturnal antidiuretic effect resulted in an anti-enuretic effect, defined as enuresis less than 1 wet night per month. In 3 patients insufficient anti-enuretic effects were obtained despite significant antidiuresis.. This pilot study clearly demonstrates that introduction of early morning furosemide results in a significantly lower nocturnal diuresis rate. Reduced diuresis associated with unchanged urinary osmolality results in decreased nocturnal osmotic excretion in compensation for increased osmotic (sodium) excretion during the daytime.

Topics: Child; Deamino Arginine Vasopressin; Diuresis; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance; Drug Therapy, Combination; Female; Follow-Up Studies; Furosemide; Humans; Male; Nocturnal Enuresis; Pilot Projects; Polyuria; Reference Values; Severity of Illness Index; Statistics, Nonparametric; Treatment Outcome; Urination; Urodynamics

To test the hypothesis that 1-desamino-8-D-arginine vasopressin (dDAVP) has an effect on prepulse inhibition (PPI) of startle in patients with primary monosymptomatic enuresis (PME), thus indicating a central effect.. Patients with PME (n = 21, age 6 to 12 years) were enrolled in a prospective, randomized, double-blinded, cross-over study. Startle reflexes and PPI were measured under dDAVP treatment versus placebo.. The data show that dDAVP has a significant effect on PPI, raising it from 38.88% under placebo to the age-related normal level of 62.6% with dDAVP treatment (P = .0127).. Our findings revive the concept of a central pathophysiology of PME and offer a different explanation for the effects of dDAVP, which not only acts on the kidney, but also is (as is AVP) a central neurotransmitter with a signal cascade on relevant reflex mechanisms.

Topics: Acoustic Stimulation; Child; Cross-Over Studies; Deamino Arginine Vasopressin; Double-Blind Method; Electromyography; Female; Humans; Male; Neural Inhibition; Nocturnal Enuresis; Reflex, Startle

To determine any possible adverse effect of 1-deamino 8-D-arginine vasopressin (DDAVP) spray on nasal cytology and mucociliary clearance in patients with nocturnal enuresis.. Twenty-two children aged 6-16 enrolled in the study. Epithelial surface cells samples were taken from the nasal mucosa and mucociliary clearance time was calculated before and 1 and 6 months after administration of DDAVP spray.. No qualitative changes in the epithelial surface cells and mucociliary clearance time were observed at 1 and 6 months after therapy.. Based on the findings of the present study, DDAVP spray can be used for 6 months in children without apparent risk of damage to the epithelial surface cells and mucociliary clearance time.

Topics: Administration, Intranasal; Adolescent; Antidiuretic Agents; Child; Cilia; Deamino Arginine Vasopressin; Female; Humans; Male; Mucociliary Clearance; Nasal Mucosa; Nocturnal Enuresis

The population pharmacokinetics of desmopressin in children with nocturnal enuresis and in healthy adults were compared using a 1-compartment model with first-order absorption and first-order elimination. In addition, the model consisted of a number of transit compartments before absorption to describe a lag-time. The model gave an adequate description of adult as well as children data and provided a statistically significant better fit to data than a standard lag-time model. The main difference in the pharmacokinetics between children and adults was the absorption delay. The pharmacokinetic difference was minor and presumably of no clinical relevance.

Topics: Administration, Sublingual; Adolescent; Adult; Age Factors; Algorithms; Antidiuretic Agents; Biological Availability; Child; Cross-Over Studies; Deamino Arginine Vasopressin; Dosage Forms; Dose-Response Relationship, Drug; Double-Blind Method; Freeze Drying; Humans; Intestinal Absorption; Metabolic Clearance Rate; Middle Aged; Models, Biological; Nocturnal Enuresis; Tissue Distribution

Nocturnal polyuria (NP) due to a suppressed vasopressin circadian rhythm is a well-documented pathogenetic mechanism in enuresis, mainly studied in monosymptomatic enuresis. A substantial percentage of patients do not respond to desmopressin. This suggests that NP may not only be related to vasopressin, but that other kidney components play a role. Solute handling and osmotic excretion have been investigated in the past, especially in refractory patients. Nevertheless, data in treatment-naïve populations with information on timing overnight are sparse. This study aims to investigate the diuresis and solute excretion in treatment-naïve patients with or without NP, with emphasis on circadian rhythms.. Retrospective analysis of 403 treatment-naïve children 5-18 years with severe enuresis (> 8 nights/2 weeks). Circadian rhythms were evaluated by a 24-h urine collection in 8 timed portions (4 day, 4 nighttime) at in-home settings. Urine volume, osmolality, and creatinine were measured. Patients were subdivided into three groups according to nocturnal diuresis (ND) and Expected Bladder Capacity (EBCage) ratio: (a) < 100%, (b) 100-129%, (c) > 130%.. All groups maintained circadian rhythm for diuresis and diuresis rates. Patients with higher ND (100-129% and > 130% EBCage) had higher daytime volumes and less pronounced circadian rhythm. In the ND group > 130% EBCage, the ND rate was higher during the first night collection and osmotic excretion was significantly higher overnight.. Overall 24-h fluid intake (reflected by 24-h diuresis) and nutritional intake (24-h osmotic excretion) might play a role in enuresis. Increased diuresis rate early in the night can be important in some patients, whereas the total night volume can be important in others. A higher resolution version of the Graphical abstract is available as Supplementary Information.

Topics: Child; Circadian Rhythm; Deamino Arginine Vasopressin; Humans; Nocturnal Enuresis; Polyuria; Retrospective Studies; Vasopressins; Water

Two central problems with the enuresis alarm are the family workload and the lack of predictors of therapy response. We wanted to look at predictors of alarm response in a setting reflecting clinical reality.. An alarm linked to a smartphone app was provided to enuretic children managed at pediatric outpatient wards. Baseline data (sex, age, daytime incontinence, urgency, previous therapies, arousal thresholds and baseline enuresis frequency) were recorded. Further information, such as enuretic episodes and actual alarm use, was gathered via the app during therapy. Therapy was given for 8-12 weeks or until 14 consecutive dry nights had been achieved.. For the 196 recruited children the outcome was as follows: full responders (FR) 18.4%, partial responders (PR) 20.4%, nonresponders (NR) 22.4% and dropouts 38.8%. We found no clear predictors of response or adherence among baseline data. But as treatment progressed responders reduced their enuresis frequency as compared to NR (week two P = 0.003, week three and onwards P < 0.001). This is further illustrated in the Figure below. Furthermore, the children unable to complete the full treatment had more non-registered nights already from the second week (week two P = 0.005, week three P = 0.002 and so on).. Anamnestic data give little predictive information regarding enuresis alarm response or adherence. Contrary to common belief neither daytime incontinence nor previous alarm attempts influenced treatment success. But after 2-4 weeks of therapy the children with a good chance of treatment success could be discerned by decreasing enuresis frequency, and the families that would not be able to comply with the full treatment showed incomplete adherence already during the first weeks.. Maybe the enuresis alarm strategy should be changed so that the treatment is reassessed after one month and only children with a high chance of success continue. This way, unnecessary frustration for the families of therapy-resistant children may be reduced.

Topics: Child; Deamino Arginine Vasopressin; Enuresis; Humans; Nocturnal Enuresis; Treatment Outcome

The alarm is the first-line treatment of nocturnal enuresis. However, the therapy is labour-intensive for both families and healthcare providers. Our aim was to see whether the treatment could be successfully used by the families, without support from healthcare providers.. An alarm linked to an application on a parent's smartphone was used. The app recorded enuretic events and gave instructions. Group A were children supported by a nurse. Group B were patients whose families had bought the alarm and downloaded the app independently.. There were 196 children in group A and 202 in group B. The percentages of full responders, partial responders, non-responders and dropouts were 18.4%, 20.4%, 22.4% and 38.8% in group A and 13.4%, 11.4%, 14.9% and 60.4% in group B. The risk for dropping out of therapy was higher in group B (p < 0.001), whereas the chance for adherent children to become dry did not differ between the groups (p = 0.905).. For families who are able to adhere to alarm therapy the chance of success is just as good when managed independently as when supported by a nurse. But the latter children will have a greater chance of adhering to the full treatment.

Topics: Child; Consumer Behavior; Deamino Arginine Vasopressin; Enuresis; Health Personnel; Humans; Nocturnal Enuresis; Prospective Studies

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.. 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.. • 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%.. • 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.

Topics: Child; Constipation; Deamino Arginine Vasopressin; Female; Humans; Male; Nocturnal Enuresis; Polyuria

One of the main medical treatment options for monosymptomatic nocturnal enuresis (MNE) is the vasopressin analog desmopressin. But not all children respond to desmopressin treatment, and no reliable treatment predictor has yet been established. We hypothesize that plasma copeptin, a surrogate marker for vasopressin, can be used to predict treatment response to desmopressin in children with MNE.. In this prospective observational study, we included 28 children with MNE. At baseline, we assessed the number of wet nights, morning, and evening plasma copeptin, and plasma sodium and started treatment with desmopressin (120 µg daily). Desmopressin was increased to 240 µg daily if clinically necessary. The primary endpoint was reduction in the number of wet nights following 12 weeks of treatment with desmopressin using plasma copeptin ratio (evening/morning copeptin) at baseline.. Eighteen children responded to desmopressin treatment at 12 weeks, while 9 did not. A copeptin ratio cutoff of 1.34 (sensitivity 55.56%, specificity 94.12%, area under the curve 70.6%, P = .07) was best at predicting treatment response, with a lower ratio indicating a better treatment response. In contrast, neither the number of wet nights at baseline (P = .15) nor serum sodium (P = .11) alone or in combination with plasma copeptin improved outcome prediction.. Our results indicate that, of our investigated parameters, plasma copeptin ratio is the best predictor for treatment response in children with MNE. Plasma copeptin ratio could thus be useful to identify children with the highest benefit of desmopressin treatment and improve individualized treatment of MNE.

Topics: Child; Deamino Arginine Vasopressin; Glycopeptides; Humans; Nocturnal Enuresis; Sodium; Treatment Outcome

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).. 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).. 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.. 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.

Topics: Child; Chromatography, Liquid; Deamino Arginine Vasopressin; Humans; Male; Metabolome; Nocturia; Nocturnal Enuresis; Polyuria; Proteome; Tandem Mass Spectrometry

We evaluated a new bedwetting alarm, GOGOband®® which utilizes real time heart rate variability (HRV) analysis and applied artificial intelligence (AI) to create an alarm that can wake the user prior to wetting. Our aim was to evaluate the efficacy of GOGOband® for users in the first 18-months of use.. A quality assurance study was conducted on data retrieved from our servers, of initial users of the GOGOband® which includes a heart rate monitor, moisture sensor, bedside PC-tablet, and a parent app. There are three sequential modes beginning with Training, Predictive mode and Weaning mode. Outcomes were reviewed and data analysis was done with SPSS and xlstat.. All 54 subjects who used the system from Jan 1, 2020, to June 2021 for more than 30 nights were included in this analysis. The mean age of the subjects is 10.1 ± 3.7 yrs. Subjects wet the bed a median of 7 (IQR6-7) nights per week prior to treatment. Severity and number of accidents per night had no impact on the ability to achieve dryness with GOGOband®. A crosstab analysis was performed which indicated that high compliant users (>80%) can remain dry 93% of the time compared to the whole group 87.7%. Overall ability to achieve 14 dry nights in a row was 66.7% (36/54) with some achieving a median of 16 14-day periods of dryness (IQR 0-35.75).. We found 93% dry night rate in high compliance users in Weaning, this translates to 1.2 wet nights per 30 days. This compares to all users who wet 26.5 nights prior to treatment and 11.3 wet nights per 30 days during Training. The ability to achieve 14 days straight of dry nights was 85%. Our findings indicate that GOGOband® provides a significant benefit to all its users reducing nocturnal enuresis rates.

Topics: Adolescent; Artificial Intelligence; Child; Deamino Arginine Vasopressin; Enuresis; Humans; Nocturnal Enuresis; Renal Agents

To analyse the clinical evolution, the therapeutic strategies and the characteristics of the patients presenting enuresis attended at our outpatient clinic.. Retrospective study of patients <14 years old(yo) diagnosed of enuresis attended at our outpatient clinic (2011-2019) and completed their follow-up (remission or aged 15). Urotherapy was offered to all patients as initial management. The therapeutic strategies were classified as: first line (desmopressin or clock alarm), second line (desmo-pressin+alarm) and third line(anticholinergics). The remission rate during follow-up, the number of consultations needed until remission and the treatments used were calculated. Statistical tests used:Kaplan-Meier, actuarial survival. Multivariate analysis:Cox regression.Statistical significance:p<0.05.. Data were collected from 125 patients (mean age: 8.6±2.45yo). Family history of enuresis was present in 38.9%. The mean follow-up was 2.37±1.55yo and the average number of consultations was 7.54±5.06. The remission rate (RE) was 84%(n=105), with a median remission interval:2.66 years (2.34-2.991[95%CI]). The average number of treatments required for remission was 2.74±1.27. RE with urotherapy alone was 20%(n=25); RE with first line:19.3%(n=17) and second line:16.7(n=11). In the remaining patients, a RE of 78.18%(n=43) was achieved by adding an anticholinergic. Patients aged > 8.7 years at the beginning of the follow-up required less time to achieve remission (p=.025). These patients had a higher RE (hazard ratio 1.15 (1.05-1.25))(p=.004). No other variables were significant.. Staged therapeutic strategies are necessary to achieve remission. Only 25% remitted with urotherapy as single treatment. RE are higher when patients are >8.7 yo once they initiate their follow up.

Topics: Adolescent; Child; Deamino Arginine Vasopressin; Humans; Nocturnal Enuresis; Retrospective Studies; Urinary Incontinence; Urology

Topics: Deamino Arginine Vasopressin; Humans; Nocturnal Enuresis; Pyrimidinones; Pyrrolidines; Solifenacin Succinate

Japanese traditional (Kampo) medicine has been empirically used for nocturnal enuresis (NE). This study aims to investigate the efficacy of one of the most popular formulas, shokenchuto (SKT). We retrospectively analyzed 110 patients with NE who were referred to our department. Following the diagnosis of NE, treatment was started with either alarm or/and desmopressin (DDAVP) therapy. Patient refractory to DDAVP monotherapy or to combination therapy consisting of DDAVP and bedwetting alarm were selected. SKT (Tsumura Co., Tokyo, Japan) extract at a dose of 2.5 g was administered orally to all intractable cases twice daily before meals. The treatment outcomes and safety were assessed. In total, 24 cases were patient refractory to DDAVP monotherapy or to combination therapy consisting of DDAVP and bedwetting alarm. SKT was highly effective in 8, effective in 7, and ineffective in 9. A significant difference was observed between ages 10 and over (P = 0.031). SKT was significantly effective as a treatment for NE in patients aged ≥10 years and could be a good alternative if alarm or DDAVP therapies are ineffective. We proposed evaluating SKT prospectively for NE.

Topics: Deamino Arginine Vasopressin; Herbal Medicine; Humans; Japan; Nocturnal Enuresis; Plants, Medicinal; Retrospective Studies

In monosymptomatic nocturnal enuresis (MNE) treatment, enuretic alarm devices are the first recommended treatment option. This study aimed to compare retrospectively the effectiveness of wearable wireless and wired alarm devices for MNE treatment in children aged 6-14 years.. All children aged 6-16 with MNE who underwent alarm therapy as outpatients were included. A wired alarm device was used from 2012 to 2015, and a wireless alarm device was used from 2016 to 2019. The primary outcomes were the dropout rates during therapy and at last follow up. The full response(14 consecutive dry nights) and the partial response rate during therapy were also assessed.. Of the 173 patients enrolled, 75 and 98 used a wired and a wireless alarm device, respectively. The dropout rate at the last visit was significantly lower in the wireless alarm group than that in the wired alarm group (6.1% vs. 20.0%; P = 0.006). The full response(FR) rate was significantly higher in the wireless alarm group than these in the wired alarm group at 4, 12, 24 weeks (4 weeks: 11.2% vs. 1.3%, P = 0.011; 12 weeks: 31.9% vs. 13.5%, P = 0.005; 24 weeks: 72.9% vs. 39.7%, P < 0.0001).. Wireless alarm therapy for MNE had lower attrition rates and a higher rate of FR than wired alarm therapy.

Topics: Child; Deamino Arginine Vasopressin; Humans; Nocturnal Enuresis; Retrospective Studies; Treatment Outcome

Nocturnal enuresis is defined as nighttime urinary incontinence occurring at least twice weekly in children five years and older. Approximately 14% of children have spontaneous resolution each year without treatment. Subtypes of nocturnal enuresis include nonmonosymptomatic enuresis and primary and secondary monosymptomatic nocturnal enuresis. Monosymptomatic enuresis is characterized by nighttime bedwetting without daytime urinary incontinence. Pathophysiology of primary monosymptomatic nocturnal enuresis may be due to sleep arousal disorder, overproduction of urine, small bladder storage capacity, or detrusor overactivity. Children with nonmonosymptomatic enuresis have daytime and nighttime symptoms resulting from a variety of underlying etiologies. An in-depth history is an integral component of the initial evaluation. For all types of enuresis, a comprehensive physical examination and urinalysis should be performed to help identify the cause. It is important to reiterate to the family that bedwetting is not the child's fault. Treatment should begin with behavioral modification, which then progresses to enuresis alarm therapy and oral desmopressin. Enuresis alarm therapy is more likely to produce long-term success; desmopressin yields earlier symptom improvement. Treatment of secondary monosymptomatic nocturnal enuresis and nonmonosymptomatic enuresis should primarily focus on the underlying etiology. Pediatric urology referral should be made for refractory cases in which underlying genitourinary anomalies or neurologic disorders are more likely. .

Topics: Behavior Therapy; Child; Deamino Arginine Vasopressin; Humans; Nocturnal Enuresis; Urinalysis; Urinary Incontinence

Topics: Antidiuretic Agents; Deamino Arginine Vasopressin; Humans; Nocturnal Enuresis; Polyuria

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.. 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.. 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.. Before desmopressin use, assessment of patients with a 24 h ABPM may be beneficial to select the method to be used for treatment.

Topics: Blood Pressure; Blood Pressure Monitoring, Ambulatory; Deamino Arginine Vasopressin; Humans; Nocturnal Enuresis; Polyuria

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.

Topics: Antidiuretic Agents; Child; Deamino Arginine Vasopressin; Enuresis; Humans; Nocturnal Enuresis; Recurrence; Retrospective Studies

Nocturnal enuresis (bedwetting) is a common disorder affecting 10-16% of 7-year-old children globally. Nocturnal enuresis is highly heritable, but its genetic determinants remain unknown. We aimed to identify genetic variants associated with nocturnal enuresis and explore its genetic architecture and underlying biology.. We did a genome-wide association study (GWAS) of nocturnal enuresis. Nocturnal enuresis cases were identified in iPSYCH2012, a large Danish population-based case cohort established to investigate mental disorders, on the basis of 10th revision of the International Statistical Classification of Diseases (ICD-10) diagnoses and redeemed desmopressin prescriptions in Danish registers. The GWAS was done in a genetically homogeneous sample of unrelated individuals using logistic regression with relevant covariates. All genome-wide significant variants were analysed for their association with nocturnal enuresis in an independent Icelandic sample from deCODE genetics. Standardised polygenic risk scores for attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder were constructed from summary statistics of large GWASs and analysed for association with nocturnal enuresis.. The GWAS included 3882 nocturnal enuresis cases and 31 073 controls. We found two loci at chromosome 6 and chromosome 13 significantly associated with nocturnal enuresis. Six genetic variants at the two loci (five variants at chromosome 6q16.2 and one variant at chromosome 13q22.3) surpassed the threshold for genome-wide significance (p<5 × 10. This study shows that common genetic variants contribute considerably to nocturnal enuresis, and it identifies potential nocturnal enuresis risk genes with roles in sleep, urine production, and bladder function. Given that available treatments target these mechanisms, any of the identified genes and their functional gene networks are potential drug targets.. The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Stanley Foundation.

Topics: Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Child; Chromosomes, Human, Pair 13; Chromosomes, Human, Pair 6; Deamino Arginine Vasopressin; Female; Genetic Loci; Genetic Variation; Genome-Wide Association Study; Humans; Male; Nocturnal Enuresis; Phenotype

Most treatments of nocturnal enuresis (NE) are targeting the main pathophysiological mechanisms, i.e., excess nocturnal urine production, bladder reservoir dysfunction and inability to awaken to a full bladder. Although many children can be effectively treated with only one treatment modality, there is a significant number of treatment-refractory cases. We experience an increasing tendency to combine treatment modalities in those children. However, there is limited evidence regarding the efficacy and safety of such strategies.. We reviewed files from all NE children seen in our outpatient incontinence clinic between January 1st and December 31st 2017 and identified children refractory to first line treatment receiving a combination of at least two treatment modalities concurrently. Age, gender, wet nights per week before treatment, follow-up time, previous treatment with desmopressin or alarm, phenotype of NE, number of simultaneous treatments tried and response as well as registered side effects during treatment was noted. We registered the outcomes and safety of the treatment modalities and evaluated prognostic factors.. We identified 59 children (13 girls) aged 6-15 yrs (mean 9.6 yrs) of whom 30 were monosymptomatic NE (MNE) and 29 were non-monosymptomatic NE (NMNE) patients. They all suffered at least three wet nights per week before treatment. In total, 38 children (61%) became dry on multimodal therapy. Eighteen children (30%) became dry on a combination of two treatment modalities, 16 (27%) on three modalities, and two (3%) on four modalities. Nine children (15%) achieved partial response whereas three (5%) showed no response despite multiple tries with combination therapies. A total of 18 children (30%) reported side effects to one or more of the modalities tried. Side effects that led to discontinuation of the treatment were uncommon (three patients).. Treatment refractory NE represents a challenge for the clinician. Although it seems possible to adequately treat refractory NE patients with multimodal treatment one should be aware of side effects as well as inform the families of the challenges in the treatment of refractory enuresis patients. Future RCT's should focus on providing further evidence for the role of multimodal therapy in NE treatment.

Topics: Adolescent; Child; Combined Modality Therapy; Deamino Arginine Vasopressin; Enuresis; Female; Humans; Male; Nocturnal Enuresis; Retrospective Studies; Urinary Bladder

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.. 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.. 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.. 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.

Topics: Arginine Vasopressin; Child; Deamino Arginine Vasopressin; Humans; Japan; Male; Nocturnal Enuresis; Polyuria

Enuresis is identified as voluntary or involuntary leakage of urine for at least three consecutive months in the daytime and/or nighttime on clothes for children older than five. Monosymptomatic nocturnal enuresis (MNE) describes nighttime wetting without daytime leakage of urine in children with no pathology in the urinary system and it is 80% more common than enuresis. Desmopressin is the most common medical treatment for MNE. The aim of this study is to retrospectively compare the effectiveness of desmopressin as monotherapy and desmopressin + oxybutynin as a combination therapy in the treatment of nocturnal enuresis.. This study retrospectively evaluated 183 patients who applied to pediatrics, pediatrics surgery and urology clinics with the complaint of nocturnal enuresis and diagnosed with primary monosymptomatic nocturnal enuresis between January 2014 and December 2019. The patients were divided into two groups (91 patients) who only received desmopressin therapy (Group 1), and those (92 patients) who received desmopressin and oxybutynin combination therapy (Group 2). Response to treatment, compliance and recurrence ratios were determined in the evaluation. Complete response was accepted as 90-100% decrease in the number of nighttime wetting, partial response was accepted as 50-90% decrease in the number of nighttime wetting and those below 50% were regarded as non-response. The 1st, 3rd, and 6th months of control data of treatment effectiveness of both groups were evaluated and their responses to treatment and the side effects of drugs were examined.. The mean age 183 patients of whom 103 were male and 80 were female was 10 (6-16) year. In the first month of control of Group 1, 71.4% had a complete cure, 8.8% had a partial cure and 19.8% had no response to treatment. In the third month of control of Group 1, 74.73% gave a complete response and were cured, 5.5% gave a partial response and 19.78% had no response. In the sixth month of Group 1, 70 patients were evaluated as complete response (79.5%), and 5 patients were evaluated as partial response (5.6%). In the first month of control of Group 2, 75% gave a complete response, 10.9% gave a partial response, 14.1% had no response to treatment. In the third month of control of Group 2, 86.9% gave a complete response, 6.52% gave a partial response, and 6.52% had no response. In the sixth month of the control of Group 2, the number of patients who did not come for control and could not be reached was 2, 83 patients out of 90 patients were evaluated as complete response (92.2%), 6 patients were evaluated as partial response (6.6%).. Desmopressin is the only FDA approved pharmacologic treatment for nocturnal enuresis. Desmopressin reduces urine production and the anticholinergic agent allows the bladder to store more urine. Therefore, combined therapy can be recommended in the MNE treatment for specially selected cases.

Topics: Antidiuretic Agents; Child; Deamino Arginine Vasopressin; Enuresis; Female; Humans; Male; Mandelic Acids; Nocturnal Enuresis; Retrospective Studies; Treatment Outcome

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.. 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.. 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).. Compliance considerably influences the beneficial effects of Desmopressin. Patients with poor therapeutic effects should be evaluated for compliance and introduced to voiding school.

Topics: Child; Child, Preschool; Deamino Arginine Vasopressin; Female; Humans; Male; Nocturnal Enuresis; Schools; Urination

To evaluate whether the efficacy of desmopressin differs between patients with and without nocturnal polyuria.. 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%.. 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.. 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.

Topics: Antidiuretic Agents; Child; Child, Preschool; Deamino Arginine Vasopressin; Enuresis; Humans; Infant; Japan; Male; Nocturnal Enuresis; Polyuria

Topics: Antidiuretic Agents; Child; Deamino Arginine Vasopressin; Humans; Japan; Nocturnal Enuresis; Polyuria

There is a high prevalence of enuresis in children with neurodevelopmental disorders, yet research regarding treatment for this group has been neglected. The efficacy of treatment using bell and pad alarm therapy is not well reported especially in children with neurodevelopmental disorders. This study sought to compare the treatment efficacy of practitioner-assisted bell-and-pad enuresis alarm therapy for children with neurodevelopmental disorders and typically developing children.. This study utilized the data of Apos et al. (2018), a retrospective medical record audit collected from multiple clinical settings across Australia. A total of 2986 patient records (3659 treatment records) were included. The participants were children aged 5-16 years, who were diagnosed with enuresis. Children with a neurodevelopmental disorder (n = 158) had a clinical diagnosis present in the medical history of attention deficit disorder, autism spectrum disorder, or intellectual disability. Children who indicated any of the following comorbidities were excluded: cerebral palsy, brain injury, malformation of the renal tract, previous bladder or renal surgery, spinal cord malformation, spinal cord trauma or tumor, or a neurodegenerative disorder. Treatment success was defined as ≥ 14 dry nights. Relapse was defined as one symptom recurrence per month post-interruption of treatment, as defined by the International Children's Continence Society definitions.. The success rate for children with neurodevelopmental disorders was 62% and typically developing children was 78%. There was no significant difference between the number of treatments received or relapse rates by those children with a neurodevelopmental disorder and typically developing children. The summary figure shows the percentage of children in each group after their first treatment who were successful (success defined as dry for ≥ 14 days), who succeeded (dry for ≥ 14 days) but then relapsed and those who showed no success. The percentage of children with no NDD who were successfully dry after the first treatment was 78%. Children with ID had success after the first treatment of 59%, the lowest of all groups analyzed.. The type of alarm therapy reported in this study is effective for treating enuresis in children with neurodevelopmental disorders.

Topics: Autism Spectrum Disorder; Child; Deamino Arginine Vasopressin; Enuresis; Humans; Neurodevelopmental Disorders; Nocturnal Enuresis; Retrospective Studies

There are many variables affecting the success of treatment in children with primary monosymptomatic nocturnal enuresis (PMNE). This study investigates the possible effect of cigarette smoke exposure on desmopressin treatment response in children with PMNE.. The medical records of pediatric patients with PMNE between February 2018 and December 2018 were retrospectively reviewed. Those who had moderate (3-5 wet nights/week) and severe (>5 wet nights/week) PMNE were included in the study. All patients received 120 mcg of sublingual desmopressin. After 3 months of therapy, treatment response was classified as complete response (100% dry night), partial response (between 50% and 99%) and non-responsiveness (<49% improvement). Partial response or non-responsiveness is considered as treatment failure. The relationship between treatment response to desmopressin and exposure to cigarette smoke was evaluated. Moreover, the other risk factors for treatment failure were investigated.. A total of 81 children with the diagnosis of PMNE, with a mean age of 9.98 ± 2.62 years, were included in the study. The frequency of passive smoke exposure at home was 53.1%. Sixty-two patients (76.5%) had severe PMNE, and the response to desmopressin decreased with severity of symptoms. Non-responsiveness to treatment, partial response, and complete response were observed in 11 (13.6%), 23 (28.4%), and 47 (58.0%) of patients, respectively. Treatment failure (n = 34, 42%) was 55.8% in children exposed to smoke and 26.4% in those who were not (p = 0.001). Although univariate analysis revealed that the severity of symptoms and smoke exposure were associated with treatment failure, in multivariate analysis, the presence of smoke exposure was the only independent risk factor (OR = 3.214, 95% CI: 0.125-0.888; p = 0.024) (Summary Table 1).. Exposure to cigarette smoke is a changeable and important risk factor that reduces the success of desmopressin treatment in children with PMNE.

Topics: Antidiuretic Agents; Child; Deamino Arginine Vasopressin; Female; Humans; Male; Nocturnal Enuresis; Retrospective Studies; Tobacco Smoke Pollution; Treatment Failure

Toilet training is a developmental task that typically can be accomplished without medical intervention. Parent counseling about it can begin approximately at the 18- to 24-month well child visit. Guidelines from the American Academy of Pediatrics recommend beginning toilet training when the child shows signs of readiness, but typically not before age 2 years; praising success using positive terms; avoiding punishment, shaming, or force; and making training positive, nonthreatening, and natural. Nocturnal enuresis is defined as urinary incontinence that occurs at night during sleep in children 5 years or older for 3 consecutive months. It is common, affecting 5%-10% of 7-year-old children in the United States. Nonpharmacologic management includes behavioral interventions (eg, limiting fluid intake before bedtime, waking the child at night to attempt to urinate, lifting the sleeping child onto the toilet and then waking him or her to urinate, bladder training to increase bladder capacity, or instituting a reward system). Bed alarms are the first-line intervention but typically are not reimbursed by health insurance. Pharmacotherapy includes desmopressin, tricyclic antidepressants, and anticholinergics. The combination of a bed alarm with pharmacotherapy can be considered as initial management or after an unsuccessful initial intervention.

Topics: Antidepressive Agents, Tricyclic; Behavior Therapy; Child; Child, Preschool; Deamino Arginine Vasopressin; Female; Humans; Infant; Male; Nocturnal Enuresis; Toilet Training

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.. 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.. 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).. Desmopressin treatment may be a feasible option for treating nocturnal enuresis with concentrated first morning urine.

Topics: Adolescent; Antidiuretic Agents; Child; Deamino Arginine Vasopressin; Female; Humans; Japan; Male; Nocturnal Enuresis; Osmolar Concentration; Treatment Outcome; Urinalysis

The case history is the primary tool when investigating the enuretic child. To further determine whether nocturnal polyuria or detrusor overactivity is present, a full voiding chart, is the method of choice. However, there is no robust evidence that daytime voiding chart data actually do predict nocturnal detrusor function.. The aim of this study was to assess the predictive value of anamnestic data and the voiding chart in the treatment of children with therapy-resistant enuresis.. The patients all suffered from enuresis resistant to first-line therapy. None of the children had daytime incontinence. In accordance with international recommendations, the children were first treated with anticholinergics. If the therapeutic effect was not satisfactory dosage was adjusted and desmopressin was added. If sufficient treatment effect was not achieved, antidepressant therapy was tried next, combined with desmopressin if needed. Since this was an evaluation of clinical practice, not a randomized trial, treatment success was graded according to family satisfaction, not the actual frequency of wet nights. Thus, only children who reported that they were completely dry were regarded as full responders and those who stated that there was a substantial and useful reduction of wet nights were labeled intermediate responders.. In total, 154 patients were included. Few and inconsistent differences were found between the groups responding or not responding to the various treatment regimens, and this was true both for anamnestic and voiding chart data (see Table). The only statistically significant findings were that responders to antidepressant therapy were older (p = 0.013) than non-responders, and patients who benefited from addition of desmopressin had a higher micturition frequency than those who did not (p = 0.027). The children who needed desmopressin as part of combination treatment to become dry did not have significantly higher nocturnal urine production than those who had no such benefit (p = 0.619). Neither the presence of urgency nor a history of previous daytime incontinence was significantly more common in children responding to anticholinergics (p = 0.375 and 0.072, respectively).. No clear and consistent differences in either anamnestic factors or voiding chart data were found between the patients responding or not responding to the various treatment regimens. Not even urgency could predict anticholinergic efficacy. Somewhat surprisingly, no association between nocturnal polyuria and desmopressin benefit was found.. In this study no prognostic value was found in anamnestic or voiding chart data in children with therapy resistant enuresis.

Topics: Child; Cholinergic Antagonists; Deamino Arginine Vasopressin; Enuresis; Humans; Nocturnal Enuresis; Prognosis; Treatment Outcome; Urinary Incontinence

Topics: Antidiuretic Agents; Child; Deamino Arginine Vasopressin; Female; Humans; Male; Nocturnal Enuresis

Topics: Antidiuretic Agents; Deamino Arginine Vasopressin; Humans; Nocturnal Enuresis; Urinary Incontinence

Primary monosymptomatic nocturnal enuresis (MNE) is a common pediatric condition and there are two firstline, evidence-based treatments available; desmopressin and the enuresis alarm. Although there are many studies comparing enuresis alarm and desmopressin treatments in the literature, most were conducted using old formulations of desmopressin.. To compare the efficacy of desmopressin MELT formulation and enuresis alarm therapy in patients with MNE.. A total of 130 patients who had primary MNE were included in the study. The patients were divided into two groups using simple randomization; desmopressin MELT (Group 1, n = 66) and enuresis alarm (Group 2, n = 64). The patients were invited for a follow-up visit at the fourth, 12th and 24th weeks of treatment. Treatment response and compliance were evaluated using bed-wetting diary and ICSS criteria.. The mean age of the patients Group 1 and 2 was 11.2 + 3.3 and 10.2 + 3.4 years, respectively (p = 0.104). Complete response rate was similar at 4th week (53% vs. 37.3%, p = 0.162) and at 12th week (68.4% vs. 68.2%, p = 0.257). The relapse rate was significantly higher in the desmopressin MELT group than in the enuresis alarm group (48.9% vs 20.5%, p = 0.007). At the end of the study ten patients were excluded from the study because of loss to follow-up and/or side effects. The overall complete response rate was significantly higher in the enuresis alarm group than in the desmopressin MELT group at the end of the study (41.3% vs 64.9%, p = 0.035). When the intention to treat analysis population was considered, similarly the complete response rate was significantly higher in the enuresis alarm group than in the desmopressin MELT group (40.9% vs 64.1%, p = 0.027).. With regard to the management of children with MNE, our study revealed that desmopressin MELT and enuresis alarm both have high efficacy rates in primary MNE treatment both at 4th and 12th week. However, overall complete response rate was better in enuresis alarm treatment at 24th week. In addition, enuresis alarm treatment also presents as a more favorable relapse rate.. Enuresis alarm presented a more permanent treatment response and a lower relapse rate than desmopressin MELT formulation.

Topics: Adolescent; Child; Clinical Alarms; Deamino Arginine Vasopressin; Enuresis; Humans; Nocturnal Enuresis; Recurrence

To test the therapeutic effects of Desmopressin (dDAVP) in primary monosymptomatic nocturnal enuresis (PMNE) treatment depending on patients'age.. The prospective research was carried out in the 2014-2018 period, during which 89 patients were observed who were treated with dDAVP due to the previously diagnosed PMNE. The patients were divided into two age groups. The first group (Group 1) consisted of 43 patients age 5 to 6, with the average age of 5.6 ± 0.5, out of whom 35 (81.4%) were boys, and 8 (18.6%) girls. The second group (Group 2) consisted of 46 patients age over 7 to 12, with the average age of 9.7 ± 1.6, out of whom 30 (65.2%) were boys, and 16 (34.8%) were girls. There was no statistically relevant difference according to sex (p = 0.086). After the 3-month treatment, all the patients in both groups were tested for the effects of dDAVP in PMNE treatment.. The average enuresis frequency in the first group (Group 1) before therapy was 26.0 ± 6.2 per month, whereas the average enuresis frequency after therapy was 11.0 ± 8.0 per month (p = 0.040). The average enuresis frequency in the second group (Group 2) before therapy was 23.1 ± 6.2 per month, whereas the average enuresis frequency after therapy was 3.8 ± 3.6 per month (p = 0.036). ANOVA data analysis of repeated measurements has indicated that there is a statistically relevant interaction between the groups (p = 0.006), i.e. enuresis frequency decreases considerably more in the second group (Group 2).. PMNE with dDAVP is noticeably more effective with patients over 7 years of age.

Topics: Child; Child, Preschool; Deamino Arginine Vasopressin; Enuresis; Female; Humans; Male; Nocturnal Enuresis; Prospective Studies; Urinary Incontinence

We investigated whether the daily salt intake of children with nocturnal enuresis influenced their response to 1-desamino-8-D-arginine vasopressin therapy.. 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.. 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).. High daily salt intake significantly reduced the efficacy of ddavp therapy for nocturnal enuresis and consumption should be controlled during treatment.

Topics: Antidiuretic Agents; Child; Deamino Arginine Vasopressin; Female; Humans; Male; Nocturnal Enuresis; Sodium Chloride, Dietary; Treatment Outcome

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.. 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.. 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).. 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.

Topics: Biomarkers; Brain-Derived Neurotrophic Factor; Child; Child, Preschool; Creatinine; Deamino Arginine Vasopressin; Female; Humans; Male; Nerve Growth Factor; Nocturnal Enuresis; Predictive Value of Tests; Treatment Outcome

This study investigated how desmopressin is prescribed to adults in Denmark.. All adult users of desmopressin over an 8-year period were identified from the Danish National Prescription Registry. Adult patients with nocturia or nocturnal enuresis (NE) were identified by indication codes for "frequent nocturnal voiding" or "involuntary nocturnal voiding", respectively. Patient demographics, desmopressin formulation and dose, and concomitant medication were investigated.. In all, 13 871 adults with nocturia and 2872 adults with chronic (i.e. >10 prescriptions) NE were given 102 547 and 43 712 desmopressin prescriptions, respectively. Across the entire patient cohort, 57% were women and mean patient age was 62 years. Over 40% of prescriptions were to elderly patients (≥65 years), and desmopressin use for adult enuresis increased with age. Orally disintegrating tablets were the most frequently used formulation (57%-65% of prescriptions), and a greater proportion of women than men used low-dose desmopressin (60 μg). Concomitant use of painkillers (opioids: 18%-26.7% of prescriptions; non-steroidal anti-inflammatory drugs: 14.2%-16.4% of prescriptions) and antidepressants (14.4%-18.1% of prescriptions) was common in both conditions, and 5.4%-9.2% of concomitant prescriptions were for overactive bladder medications.. This study provides insights into desmopressin use among Danish adults. Nearly half the prescriptions were to patients aged ≥65 years, despite historical manufacturer recommendations that desmopressin be restricted to patients <65 years of age. NE is considered a childhood condition, but desmopressin use for adult NE increased with age. A greater proportion of desmopressin prescriptions to women than men were for the lowest dose, consistent with greater sensitivity to desmopressin in women.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Antidiuretic Agents; Deamino Arginine Vasopressin; Denmark; Drug Prescriptions; Female; Humans; Male; Middle Aged; Nocturia; Nocturnal Enuresis; Registries; Sex Factors; Young Adult

To introduce a new protocol for patients with primary nocturnal enuresis to increase efficacy of treatment and decrease relapse rate.. A prospective study was done on 185 children diagnosed with nocturnal enuresis between the years 2007 and 2014. Inclusion criteria consisted of age >5 years, monosymptomatic enuresis or non-monosymptomatic enuresis, strict abidance by the protocol, and follow-up >24 months. Exclusion criteria consisted of secondary enuresis, poor compliance to protocol, and neurogenic bladder. Participants were started on combination therapy of desmopressin 120 µg (MELT formula) once per day and propiverine 7.5 mg twice per day, which were then adjusted as per their response to therapy and our designed protocol. Outcome was defined as per the International Children Continence Society (ICCS) latest definitions.. One hundred twenty-two patients satisfied the inclusion criteria and were included in the study with a median age of 9 years (range 5-19 years). The mean follow-up time was 62 months (range 25-114 months). Our protocol showed an overall complete success of 87% with failure and relapse of 13%. The success rate of patients needing 120 µg desmopressin as maintenance therapy to achieve dryness was 92.7% as compared to 65% success in patients needing a higher dose of desmopressin to achieve dryness (P < .05). Age, gender, and type of primary nocturnal enuresis had no effect over success (all P > .05).. Adopting combination therapy along with structured withdrawal as per our protocol showed higher success rates and lower relapses in primary nocturnal enuretic children.

Topics: Antidiuretic Agents; Benzilates; Child; Child, Preschool; Deamino Arginine Vasopressin; Drug Therapy, Combination; Female; Humans; Male; Muscarinic Antagonists; Nocturnal Enuresis; Prospective Studies; Treatment Outcome

Topics: Acupuncture Therapy; Child; Deamino Arginine Vasopressin; Humans; Nocturnal Enuresis

The nocturnal polyuria is considered a significant predictive value for response to desmopressin. The cutoff value useful to define nocturnal polyuria is still a matter of debate. Moreover, it is current notion that maximal voided volume (MVV) could be used as a predictor for desmopressin response.. The objective of this study was to assess the impact of different definitions of nocturnal polyuria (and of its frequency) and MVV in predicting the response to desmopressin.. A total of 103 patients with frequent monosymptomatic nocturnal enuresis (≥4 wet nights/week) were enrolled. A bladder diary over a 4-day period was collected. The MVV was defined as the highest micturition volume detected at bladder diary. Nocturnal diuresis was measured in 5 wet nights. Then, patients were administered with 120 mcg of sublingual desmopressin. After 2 months, if there was no complete response, the dose was increased to 240 mcg. Nocturnal polyuria was defined as follows: 1.Definition 1: nocturnal urine production >130% of the expected bladder capacity (EBC). 2. Definition 2: >100% EBC. 3. Definition 3: > 20×(age + 9) mL. The primary outcome was 'response to desmopressin' after 3 months of treatment.. Fifty-three patients responded to desmopressin. Comparing the responses to desmopressin on the basis of the three definitions of nocturnal polyuria, no significant difference was found. There was no cutoff value of nocturnal polyuria expressed as %EBC useful in providing a significant receiver-operating characteristic (ROC) curve. The area under the ROC curve for MVV expressed as %EBC was 0.67 (95% confidence interval [CI], 0.54-0.80; p = 0.01). A MVV >103.1% of EBC had 78.8% (95% CI, 61.1-91.0) sensitivity and 47.5% (95% CI, 31.5-63.9) specificity for predicting response to desmopressin. Among the patients with nocturnal polyuria according to definition 1, a higher percentage of subjects with nocturnal polyuria in 4 out of 5 or 5 out of 5 nights responded to desmopressin, compared with other patients. Patients presenting with nocturnal polyuria according to definition 3 in 5 out of 5 nights showed a 100% of response to desmopressin. At multivariate analysis, the only significant odds ratio (OR) to respond to desmopressin was that of patients with nocturnal polyuria according to definition 1 in >3 nights (OR = 7.1, 95% CI, 1.3-40.3).. The presence or absence of nocturnal polyuria-according to all three definitions-in at least one night was not effective in predicting the response to desmopressin. Predictors of desmopressin response were nocturnal polyuria in >3 out of 5 wet nights according to definition 1 and in 5 out of 5 wet nights according to definition 3.

Topics: Antidiuretic Agents; Child; Deamino Arginine Vasopressin; Female; Humans; Male; Nocturnal Enuresis; Polyuria; Prospective Studies; Recurrence; Treatment Outcome

Previous studies indicated that the prevalence of constipation in enuretic patients is higher than that in the general population. Several studies have revealed that successful treatment of constipation may be helpful in resolving enuresis. However, constipation affecting the efficacy of desmopressin in treating enuresis remains to be clarified.. This study aimed to determine whether the presence of constipation is associated with the efficacy of desmopressin in treating enuresis.. Patients diagnosed with nocturnal enuresis (NE) were studied prospectively. Treatment responses in different stratified groups of patients with NE were compared by Chi-squared tests or Wilcoxon rank sum test. A logistic regression model was performed to investigate the relationship between the possible factors and the effectiveness of desmopressin.. In children with severe enuresis, patients with constipation had significantly lower complete response rate compared with patients without constipation. The presence of constipation was always related to the effectiveness of desmopressin whether in monosymptomatic NE or non-monosymptomatic patients with NE. With stratification for dose of desmopressin, non-constipated patients who received 0.2 mg of desmopressin had significantly higher complete response rate than patients with constipation. However, in subgroups of mild to moderate NE and 0.4 mg desmopressin, constipation was not associated with treatment response of enuresis. Logistic regression analysis revealed that constipation was significantly related to the effectiveness of desmopressin.. This study confirmed the negative effects of constipation in response to desmopressin in patients with NE. To the best of authors knowledge, this work is the first study to evaluate the relationship of constipation in enuretic patients and the efficacy of desmopressin.. The presence of constipation negatively affects the response to desmopressin in patients with NE, especially in patients with severe enuresis and in patients prescribed with low dose of desmopressin.

Topics: Adolescent; Antidiuretic Agents; Child; Child, Preschool; Constipation; Deamino Arginine Vasopressin; Female; Humans; Male; Nocturnal Enuresis; Prospective Studies; Treatment Outcome

Topics: Child; Deamino Arginine Vasopressin; Enuresis; Humans; Nocturnal Enuresis; Urinary Incontinence

The aim of this study was to evaluate the effectiveness of treatment with methylphenidate or desmopressin (dDAVP) in patients with comorbid attention-deficit/hyperactivity disorder (ADHD) and enuresis.. We enrolled 103 patients affected by ADHD and 125 patients with monosymptomatic nocturnal enuresis (NE). Data were collected between January 2014 and December 2015. The study was carried out in compliance with the Helsinki Declaration.. About children with ADHD, 9/103 (8.7%) were also suffering from NE; of those 8/9 followed treatment with methylphenidate and cognitive behavioral therapy. After 3 months 2/8 (25%, CI 95%: 8-65%) showed improvements, remaining 75% has been increased dosage of methylphenidate. After 6 months a response was achieved in 6/8 (75%, CI 95%: 35-96%) children and 1/8 was lost to follow-up. Furthermore the drug withdrawal showed a recurrence of symptoms both ADHD and NE in 1/7 (14.3%, CI 95%: 0.3-57%) vs. 6/7 (85.7%, CI 95%: 42-99%) that not presented recurrences. About children with NE enrolled at Campus Bio-Medico University it was found that 4/125 (3.8%) children were also suffering from ADHD; 3/4 (75%) treated with dDAVP and motivational therapy, of those 2/3 (66.7%, CI 95%: 9-99%) showed no improvements of symptoms vs. 1/3 (33.3%, CI 95%: 0.8-90%) that showed partial response with a reduction of wet-nights.. It is important the service of recruitment of patients with NE. In fact considering NE in a Child Neuropsychiatry Service where patients belong to a diagnosis of ADHD and NE is an incidental finding, this one is not considered as the addressee of treatment, but the therapy is directed to the neuro-behavioral problem using specific drugs and therapies, which are resolutive in the enuretic disorder.

Topics: Adolescent; Antidiuretic Agents; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Child, Preschool; Deamino Arginine Vasopressin; Female; Follow-Up Studies; Humans; Male; Methylphenidate; Nocturnal Enuresis; Prospective Studies; Retrospective Studies; Treatment Outcome

Desmopressin is a long-established treatment for nocturnal enuresis with clear guidelines regarding its usage. A sex difference in renal sensitivity has recently been reported in adults. The objective of this study was to investigate real-life desmopressin prescription in the Danish pediatric population, and prescription patterns which may reflect a sex difference in pediatric usage. Formulation, dose, treatment duration, and safety (hyponatremia) were investigated. 40,596 children received 214,220 desmopressin prescriptions between 2004 and 2011 in the Danish National Prescription Registry. Data were linked to hyponatremia diagnoses from the National Patient Registry. Although the lowest recommended dose of desmopressin oral lyophilisate is 120 μg, around a fifth of children were prescribed 60 μg for long-term use. A greater proportion of girls (22.6%) than boys (19.8%) received this low dose. Treatment duration was longer for boys than girls on oral lyophilisate (mean 489-524 vs. 414-462 days) and tablet (0.1 mg: 204 vs. 161 days). Prescribed daily dose was consistent with time between prescriptions, indicating no significant drug holidays. There were no admissions for hyponatremia during the observation period.. Danish national prescription data on pediatric desmopressin dosage are consistent with a greater sensitivity to desmopressin in girls than boys. Further studies are required. What is Known: • Desmopressin has been used for pediatric nocturnal enuresis for decades • Recent evidence suggests a sex difference in desmopressin sensitivity in adults What is New: • For the first time, desmopressin prescription practices in nocturnal enuresis are documented for an entire country • A higher proportion of girls than boys received a low dose of desmopressin, consistent with the sex difference in sensitivity reported in adults.

Topics: Adolescent; Antidiuretic Agents; Child; Child, Preschool; Deamino Arginine Vasopressin; Denmark; Drug Administration Schedule; Drug Compounding; Drug Dosage Calculations; Female; Guideline Adherence; Humans; Male; Nocturnal Enuresis; Practice Guidelines as Topic; Practice Patterns, Physicians'; Registries; Sex Factors

The first-line drug therapy for patients with nocturnal enuresis (NE) associated with nocturnal polyuria and normal bladder function is desmopressin (dDAVP).. To evaluate if increasing dose of oral desmopressin lyophilisate (MELT) can improve response rates to dDAVP and is useful in enuretic children.. We enrolled a total of 260 children all diagnosed with NE. Enuretic children were treated with increasing MELT at a dose of 120, 180 and 240 mcg a day.. We included in our study a total of 237 children, 164 males (69.2%) and 73 females (30.8%) aged between 5 and 18 years (mean age 10.32 ± 2.52 years). Of the 237 patients enrolled in the study and treated with MELT 120 mcg, a full response was achieved in 135 (56.9%). A partial response was achieved in 21 (8.9%) patients, therefore the dose was increased up to 180 mcg, with further improving symptoms (14.3%) or full response (9.5%), and up to 240 mcg, without usefulness.. MELT at the dose of 120 mcg resulted efficacy and safety; the increased dose up to 180 mcg resulted poorly efficacy; finally, the further increase up to 240 mcg did not improve the symptoms with the increased risk of side effects.

Topics: Administration, Oral; Adolescent; Child; Child, Preschool; Deamino Arginine Vasopressin; Dose-Response Relationship, Drug; Female; Humans; Male; Nocturnal Enuresis; Renal Agents; Treatment Outcome

Nocturnal enuresis - or bed-wetting - is one of the most common chronic conditions of childhood. It has a significant effect on the quality of life of affected children and their families and is associated with several comorbidities, some of which resolve on successful treatment. The causes of this troublesome condition are explored and the principles of assessment and treatment are discussed with reference to National Institute for Health and Care Excellence guidance as well as research. Response to treatment resistance is considered and appropriate onward referral discussed.

Topics: Adolescent; Antidiuretic Agents; Child; Child, Preschool; Deamino Arginine Vasopressin; Humans; Needs Assessment; Nocturnal Enuresis; Patient Acceptance of Health Care; Quality of Life; Treatment Outcome

Enuresis (bedwetting) is common in school-aged children and can impact health, psychosocial well-being and quality of life. Although effective treatment is available, treatment resistance is encountered in about 50%. This paper discusses the management of treatment-resistant enuresis from a multidisciplinary perspective. Causes of treatment resistance include lower urinary tract problems, constipation, incorrect alarm training techniques, sleep disorders including sleep apnoea and psychological comorbidities. Practical suggestions to address treatment resistance are offered utilising expertise from clinicians from different disciplines.

Topics: Antidiuretic Agents; Child; Clinical Alarms; Constipation; Deamino Arginine Vasopressin; Humans; Nocturnal Enuresis; Urinary Bladder, Overactive

Nocturnal enuresis is the most common type of urinary incontinence in children. The pathophysiology of the condition is complex with excess nocturnal urine production, bladder reservoir dysfunction and failure to wake up to the sensation of a full bladder, being important elements. The condition can be successfully treated in most children; desmopressin and the enuresis alarm are both effective first-line treatments. Tailoring the treatment based on the clinical characterisation of the patients can improve the outcome.

Topics: Child; Deamino Arginine Vasopressin; Humans; Nocturnal Enuresis; Urinary Bladder; Urinary Incontinence

The general objective is to adapt recommendations on monosymptomatic primary enuresis (ME) to the regional context. The instruments used were “Guide for the Adaptation of Clinical Practice Guidelines” and “Guidelines for creation of Consensus” (Sociedad Argentina de Pediatría).\ ME is called intermittent urinary incontinence during the sleep of children > 5 years of age, with no other symptoms of the urinary tract. It is differentiated from non-monosymptomatic enuresis, defined by the presence of other symptoms of the lower urinary tract, mainly during the day. The ME is a transitory condition with spontaneous resolution so the decision to start treatment must be agreed with the child and their family environment. The primary care pediatrician should be the first contact with a child with ME, who implements the initial general behaviors and eventual indication of specific first-line medication, such as alarm and desmopressin.. El objetivo general es adaptar las recomendaciones del abordaje de enuresis primaria monosintomática (EM) al contexto regional. Se utilizaron los instrumentos “Guía para la adaptación de guías de práctica clínica” y “Lineamientos para la elaboración de consensos” (Sociedad Argentina de Pediatría).\ EM se denomina a la incontinencia urinaria intermitente durante el sueño en niños > 5 años de edad, sin otro síntoma urinario. Se diferencia de la enuresis no monosintomática, que se acompaña de otros síntomas del tracto urinario bajo, principalmente, durante el día. La EM es una afección transitoria y de resolución espontánea, por lo que la decisión de iniciar tratamiento debe ser consensuada con el niño y su entorno familiar.\ El pediatra de atención primaria debe ser el primer contacto con un niño con EM, quien implemente las conductas generales iniciales y la eventual indicación de medicación específica de primera línea, como alarma y desmopresina

Topics: Antidiuretic Agents; Child; Deamino Arginine Vasopressin; Humans; Nocturnal Enuresis; Pediatricians; Practice Guidelines as Topic

Topics: Antidiuretic Agents; Child; Clinical Alarms; Combined Modality Therapy; Deamino Arginine Vasopressin; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Nocturnal Enuresis; Solifenacin Succinate; Treatment Outcome

To investigate renal concentrating ability after long-term fast-melting oral desmopressin lyophilisate treatment in children with monosymptomatic nocturnal enuresis.. The present retrospective study involved 58 children (43 boys, 15 girls; aged 6-12 years) with nocturnal enuresis receiving oral desmopressin lyophilisate. After treatment for 4 weeks with a complete response, patients were placed on a reduced dose of 120 μg on alternate days. Moring urine osmolality was measured using urine samples obtained after medication and non-medication dry nights. Patients who experienced ≥1 wet nights/month during alternate-day oral desmopressin lyophilisate treatment or within 6 months after its cessation were assigned to the relapse group, whereas those who experienced <1 wet night/month were assigned to the continued success group.. The continued success and relapse groups included 41 and 17 patients, respectively. The mean duration of treatment was 18.5 and 18.3 months in the continued success group and relapse group, respectively. There was no significant difference in morning urine osmolality after medication nights between the continued success and relapse groups; however, morning urine osmolality after non-medication nights was significantly higher in the continued success group than in the relapse group (P < 0.0001). Similarly, nocturnal urine volume was significantly higher in the relapse group than in the continued success group (P = 0.046).. These results suggest that patients receiving long-term oral desmopressin lyophilisate treatment develop increased nocturnal renal concentrating ability, which results in sustained dryness even after treatment cessation.

Topics: Administration, Oral; Antidiuretic Agents; Child; Deamino Arginine Vasopressin; Female; Humans; Kidney; Kidney Concentrating Ability; Male; Nocturnal Enuresis; Osmolar Concentration; Recurrence; Retrospective Studies; Time Factors; Treatment Outcome; Urine

The aim of the present study was to investigate the prevalence of primary monosymptomatic nocturnal enuresis (PMNE) and its associated factors in a major referral centre for nocturnal enuresis in the City of Abu Dhabi. Children referred to the Pediatric Continence Clinic of Department of Pediatric and Urology Surgery at Al Noor Hospital, Abu Dhabi (UAE), between January 2014 and January 2016 for the suspected diagnosis of NE were considered. The inclusion criteria of our study were: age 5-14 years; full medical history and physical examination; urine dipstick to exclude glycosuria and proteinuria; completion of diagnostic urological work-up; final diagnosis of PMNE. Parents were encouraged to follow a program on urotherapy. All children underwent renal and bladder ultrasound, abdominal X-ray and uroflowmetry with electromyography. Constipation was treated, if present. 39 patients had a diagnosis of PMNE. A constipation was present in 17 children (43.6%). Statistical analysis documented a higher incidence of PMNE in the male groups. 38 out of 39 children (97.4%) resolved PMNE, 14 following urotherapy and 24 required medical therapy with desmopressin. Our experience clearly confirms a higher prevalence rate of PMNE in boys than in girls. In the study population, the large intake of dry and reducedin- fibers foods, the excessive intake of carbonated drinks and the hot climatic condition might negatively influence the incidence of fecal retention and the subsequent PMNE. A multi-modal assessment seems to be effective in the management of PMNE, showing a very high rate of resolution.

Topics: Antidiuretic Agents; Child; Constipation; Deamino Arginine Vasopressin; Female; Humans; Male; Nocturnal Enuresis; Prevalence; Sex Distribution; United Arab Emirates

To evaluate the clinical results of monotherapy with combination therapy in treatment of primary monosymptomatic nocturnal enuresis (PMNE) in children.. Between December 2008 and May 2013, we reviewed the records of 176 children with PMNE. The monotherapy group received 120 micrograms of desmopressin melt whereas the combination therapy group received 120 micrograms of desmopressin melt plus 1-2 mg oral tablet of tolterodine. The degree of response was evaluated at 1-3 months during the treatment and 6 months after complete cessation of treatment protocol.. Between 176 children, 84 and 92 patients received monotherapy and combination therapy, respectively. There were no statistical differences in gender, age, or baseline monthly frequency of PMNE between the two groups. At baseline, patients had an overall mean of 23.6 ± 5.6 wet nights per month, which decreased to 10.8 ± 5.6 and 7.3 ± 5.3 in monotherapy group and 8.9 ± 9.5 and 3.3 ± 4.9 in combination therapy group at 1 and 3 months after treatment. The rates of Complete plus Partial Response to treatment at 1 and 3 months for monotherapy and combination therapy group were 63.1% and 73.9% vs 72.5% and 93.47% (P value .12 vs .006). The relapse of PMNE 6 months after complete cessation of treatment was 16.39% and 9.09% for monotherapy vs combination therapy group.. This study supports the efficacy of combination therapy with desmopressin melt plus oral tolterodine over monotherapy with desmopressin melt in the first-line treatment of PMNE in children.

Topics: Antidiuretic Agents; Child; Combined Modality Therapy; Deamino Arginine Vasopressin; Drug Therapy, Combination; Female; Humans; Male; Nocturnal Enuresis; Retrospective Studies; Tolterodine Tartrate; Urological Agents

Topics: Antidiuretic Agents; Deamino Arginine Vasopressin; Enuresis; Humans; Nocturnal Enuresis; Urinary Incontinence

There is a high comorbidity between nocturnal enuresis, sleep disorders and psychological problems. The aim of this study was to investigate whether a decrease in nocturnal diuresis volume not only improves enuresis but also ameliorates disrupted sleep and (neuro)psychological dysfunction, the major comorbidities of this disorder.. In this open-label, prospective phase IV study, 30 children with monosymptomatic nocturnal enuresis (MNE) underwent standardized video-polysomnographic testing and multi-informant (neuro)psychological testing at baseline and 6 months after the start of desmopressin treatment in the University Hospital Ghent, Belgium. Primary endpoints were the effect on sleep and (neuro)psychological functioning. The secondary endpoint was the change in the first undisturbed sleep period or the time to the first void.. Thirty children aged between 6 and 16 (mean 10.43, standard deviation 3.08) years completed the study. The results demonstrated a significant decrease in periodic limb movements during sleep (PLMS) and a prolonged first undisturbed sleep period. Additionally, (neuro)psychological functioning was improved on several domains.. The study demonstrates that the degree of comorbidity symptoms is at least aggravated by enuresis (and/or high nocturnal diuresis rate) since sleep and (neuro)psychological functioning were significantly ameliorated by treatment of enuresis. These results indicate that enuresis is not such a benign condition as has previously been assumed.

Topics: Child; Deamino Arginine Vasopressin; Humans; Nocturnal Enuresis; Polyuria; Prospective Studies

Topics: Antidiuretic Agents; Deamino Arginine Vasopressin; Enuresis; Humans; Mandelic Acids; Nocturnal Enuresis; Renal Agents

Nocturnal enuresis is a common pediatric condition with limited treatment options. In older children, pharmacologic therapy is often the preferred treatment. Pharmacologic therapies including desmopressin (DDAVP) or imipramine are effective in 40-50% of children. However, imipramine has serious safety concerns. Desmopressin in combination with a fixed dose anticholinergic has been shown to be useful in individuals who fail desmopressin monotherapy, but still fails to achieve success rates greater than 60%.. The goal was to explore the efficacy and safety of using combination therapy desmopressin plus oxybutynin with increasing dose of oxybutynin in patients refractory to standard combination therapy.. This was a single institution, IRB-approved, retrospective chart review of 61 patients (ages 7-18 years) including those with monosymptomatic primary nocturnal enuresis and non-monosymptomatic enuresis with controlled daytime voiding symptoms (CDVS) treated initially with desmopressin. All patients who failed initial therapy with desmopressin were started on combination therapy desmopressin (0.6 mg) plus standard dose (5 mg) oxybutynin. In patients who failed standard combination therapy, the dose of oxybutynin was titrated upwards until a response or the maximum dose of 10 mg was achieved. Demographic and medical history data were evaluated to determine predictive factors associated with response/failure to different therapy groups.. The use of escalating doses of oxybutynin in combination with desmopressin achieved an overall response rate of 96.7% defined as a 2-week period without any enuretic events following initiation of treatment. Low-dose combination therapy (LDCT) (0.6 mg of desmopressin+5 mg of oxybutynin) had a response rate of 68% (Table). Advanced dose combination therapy (ADCT) (0.6 mg of desmopressin+7.5-10 mg of oxybutynin) had a response rate of 75.0%. A statistically significant relationship was found correlating both attention deficit disorder/attention-deficit hyperactivity disorder(ADD/ADHD) and CDVS with failure on monotherapy. No patients in the study reported any adverse events or side effects from the medications.. The overall success rate of 96.7% with titrated doses of oxybutynin in combination with desmopressin is considerably higher than the response rates on fixed dose combination therapy quoted in the literature and supports the need for further evaluation in larger studies. Additionally, we found a statistically significant association between monotherapy failure and children with either ADD/ADHD or controlled daytime voiding symptoms. Our study is limited by small numbers and larger studies are needed to confirm these results.. Our results suggest that ADCT is a safe and effective treatment option for primary nocturnal enuresis refractory to standard and low-dose combination therapy.

Topics: Adolescent; Antidiuretic Agents; Attention Deficit Disorder with Hyperactivity; Child; Deamino Arginine Vasopressin; Drug Therapy, Combination; Female; Humans; Male; Mandelic Acids; Muscarinic Antagonists; Nocturnal Enuresis; Retrospective Studies

Topics: Circadian Rhythm; Deamino Arginine Vasopressin; Enuresis; Humans; Nocturnal Enuresis; Polyuria; Urinary Tract Physiological Phenomena

Topics: Antidiuretic Agents; Clinical Alarms; Deamino Arginine Vasopressin; Female; Humans; Male; Nocturnal Enuresis

Topics: Antidiuretic Agents; Antipsychotic Agents; Aripiprazole; Autistic Disorder; Child; Deamino Arginine Vasopressin; Humans; Male; Nocturnal Enuresis

Nocturnal enuresis (NE) is a very common multifactorial pediatric disorder and in children with­out any other lower urinary tract symptoms is defined as monosymptomatic NE (MNE). Pharmacologi­cal, psychological/behavioral, and alternative interventions are commonly used and the first-line drug ther­apy for patients with MNE is desmopressin (dDAVP) but the response rate is less than 40-60% and the relapse rate is about 50-80% after treatment. Many studies show that some foods and beverages can promote diuresis or bladder irritability, which in some people can exacerbate bladder symptoms and NE. The pres­ent study aimed to compare the efficacy of combined specific dietary advices and dDAVP vs dDAVP alone.. We enrolled in the study 172 patients affected by MNE between January 2013 and May 2014, of these 35 were excluded. The inclusion criterion was primary MNE and exclusion criteria included non-MNE, secondary MNE and lactose intolerance. Children were treated with dDAVP at a dose of 120 μg a day and were randomized to receive dietary recommendations. They were asked to fill out a char­ter depicting their wet and dry nights for the period of treatment. Sixty-seven patients were randomly as­signed to receive dDAVP and dietary advices (group A) and 70 patients to receive dDAVP alone (group B).. We included in our study 137 children, 102 (74.5%) male, and 35 (25.5%) female, aged be­tween 5 and 14 years. Our results show a higher response rate and a lower number of relapse in group A vs group B with 67.2% of responders in group A vs 58.6% in group B, after 3 months of ther­apy and 31.1% of relapse in group A vs 46.3% in group B one month, after the end of treatment.. Our results show the effectiveness of specific dietary advices in the manage­ment of primary MNE. However further studies are needed to determine whether the differ­ence between therapy with combined dietary recommendations and dDAVP vs dDAVP alone.

Topics: Adolescent; Antidiuretic Agents; Child; Child, Preschool; Cognitive Behavioral Therapy; Deamino Arginine Vasopressin; Diet; Female; Follow-Up Studies; Humans; Male; Nocturnal Enuresis; Nutrition Assessment; Random Allocation; Treatment Outcome; Urination

Secondary nocturnal enuresis is generally seen between 5 and 7 years of age and it is rarely encountered when compared with the primary incontinence. Patients with suggested diagnosis of secondary nocturnal enuresis should be examined for neurological and spinal anomalies and diabetes mellitus, diabetes insipidus, renal failure and urinary tract infection should be ruled out in differential diagnosis (1-3). Herein, we are presenting case reports of adolescent patients with secondary nocturnal enuresis refractory to medical therapy and developed after in-vehicle and extravehicular accidents.

Topics: Accidents, Traffic; Adolescent; Antidiuretic Agents; Behavior Therapy; Child; Deamino Arginine Vasopressin; Diagnosis, Differential; Female; Humans; Nocturnal Enuresis; Risk Factors; Stress Disorders, Post-Traumatic; Time Factors; Treatment Outcome

To investigate the relevance of enuresis subtyping for selection of treatment modality and for long-term outcome in a large consecutive patient cohort.. We included all patients referred for urinary incontinence during a 5-year period but excluding recurrent urinary tract infections (UTI). Type and severity of incontinence, prior history, results of examinations performed, number of visits, and effect of all treatments provided, were included in a clinical database.. Seven hundred twenty children aged 4-16 years (mean 8.5 ± 2.2 years, 239 girls) were included in the analysis (42% with monosymptomatic (MNE), 55% with non-MNE, and 3% with isolated daytime incontinence). Initial evaluation revealed only few underlying causes (one neurological and eight anatomical). Investigations showed significant differences between MNE and non-MNE patients as both maximal voided volume and nocturnal urine volume was lower in non-MNE patients (P < 0.001). Follow-up for average 1,587 days (3.4 years) was performed in 660 (92%) patients. A higher number of visits and a longer treatment period were needed for non-MNE patients (on average 4.7 ± 2.8 visits) than MNE patients (3.1 ± 1.6 visits, P < 0.001). The most common treatment regimen that resulted in dryness in both MNE (40%) and non-MNE (36%) was the alarm system. Interestingly, of the 539 patients who initially were referred due to desmopressin resistance 177 (33%) of these were dry on desmopressin monotherapy.. The study indicated that MNE and non-MNE are two distinct disease entities with different optimal treatments and showed that the latter patients are more difficult and time-consuming to manage.

Topics: Adolescent; Adrenergic Uptake Inhibitors; Antidiuretic Agents; Biofeedback, Psychology; Child; Child, Preschool; Cohort Studies; Deamino Arginine Vasopressin; Diurnal Enuresis; Enuresis; Female; Follow-Up Studies; Humans; Imipramine; Male; Mandelic Acids; Nocturnal Enuresis; Urinary Bladder, Overactive; Urological Agents

Desmopressin 120 μg oral lyophilisate and 200 μg tablet are considered bioequivalent, based on extrapolation of studies in a limited number of adults and on one dose-finding study of desmopressin oral lyophilisate in children. However, no comparative pharmacokinetic study in children was executed confirming this statement. No data are available on the influence of food intake on the bioavailability of desmopressin tablet in a pediatric setting, although studies in adults have documented that food intake results in a significantly lower desmopressin plasma concentration. In this study, we analyzed plasma concentrations of desmopressin oral lyophilisate and tablet with concomitant food intake. Twenty-three children with monosymptomatic nocturnal enuresis (mean age, 12.7 years) were recruited. Two tests were performed on two separate days in identical conditions with a standardized food and fluid intake. Desmopressin was administered as desmopressin tablet or desmopressin oral lyophilisate immediately after a meal. Desmopressin plasma concentration was measured at 1 h, 2 h, and 6 h postdosing. No significant difference in plasma concentration of 120 μg desmopressin oral lyophilisate and 200 μg tablet was demonstrated, even with concomitant food intake. A significant difference in variability was found, identifying a smaller variance for desmopressin oral lyophilisate plasma concentrations at all time points. This study demonstrates comparable plasma levels for desmopressin oral lyophilisate, despite the lower dose. The dosage for desmopressin oral lyophilisate is more predictable due to the significantly smaller variance. Therefore, desmopressin oral lyophilisate seems more suitable, especially in the younger age group for which time interval between dinner and drug administration is limited.

Topics: Administration, Oral; Adolescent; Biological Availability; Child; Cross-Over Studies; Deamino Arginine Vasopressin; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Food-Drug Interactions; Freeze Drying; Humans; Male; Metabolic Clearance Rate; Nocturnal Enuresis; Tablets; Therapeutic Equivalency

The aim of this study was to compare the efficacy of combination therapy with desmopressin and an anticholinergic to desmopressin monotherapy for the first-line treatment of children with primary monosymptomatic nocturnal enuresis (PMNE).. A total of 98 children with PMNE (male:female 71:27) aged 5-16 (mean age 7.18 ± 1.8) years were retrospectively analyzed. The patients were divided into two groups: the monotherapy group (n = 49) was given oral desmopressin alone, and the combination therapy group (n = 49) was given desmopressin plus an anticholinergic (propiverine 10 mg) as a first-line treatment. The two groups were matched according to the following criteria: age, gender, and baseline frequency of nocturnal enuresis. The efficacy was evaluated by International Children's Continence Society criteria at 1 and 3 months after treatment initiation.. The combination therapy group showed a higher rate of complete response than the monotherapy group (20.4 vs. 6.1% at 1 month of treatment; 46.9 vs. 22.4% at 3 months of treatment). In terms of success (response and complete response), there was a significant difference between the two groups after 3 months of treatment (P = 0.002).. Our results indicate that combination therapy with desmopressin plus an anticholinergic is quicker and more effective than desmopressin monotherapy in reducing PMNE.

Topics: Adolescent; Child; Child, Preschool; Cholinergic Antagonists; Deamino Arginine Vasopressin; Drug Therapy, Combination; Female; Humans; Male; Nocturnal Enuresis; Retrospective Studies

Alarm therapy is a long-established first-line therapy for nocturnal enuresis (NE). Desamino-arginine vasopressin (dDAVP) as alternative first-line therapy was shown to increase the prepulse inhibition (PPI) of startle reflexes, thus supporting the hypothesis of a maturational delay of reflex inhibition in NE. Effects of alarm therapy on PPI have not yet been investigated.. The PPI of startle reflexes was measured in 20 children with NE (13 boys, 7 girls, median age 8.5 years, range 5-13) before and after at least 6 weeks of alarm treatment and compared with repeated PPI measurements in 11 healthy controls (7 boys, 4 girls, median age 8 years, range 6-13).. In the NE patients, PPI increased from a median baseline of 20-46% under alarm therapy (p = 0.005), with a reduction from a median of 7 to 2 wet nights per week (p = 0.002). The controls showed no difference in PPI (52% median at first, 40% at second measurement, p = 0.966).. The increase of PPI trough alarm therapy was comparable with that under dDAVP, suggesting an analogous method of action and explaining the alternative or synergistic effect of both therapies. In addition, it further substantiates the hypothesis of a maturational delay of reflex control in NE.

Topics: Adolescent; Child; Child, Preschool; Deamino Arginine Vasopressin; Female; Humans; Male; Nocturnal Enuresis; Pilot Projects; Prepulse Inhibition; Reflex, Startle

To describe the natural history of patients with nocturnal enuresis (NE) during a 10-year period and to evaluate possible impact of comorbid conditions on the persistence of NE.. Ninety-five children (male to female ratio [M:F] 65:30), aged at first visit between 6 and 21 years were included in this study. Of study subjects 75 had primary monosymptomatic nocturnal enuresis (PMNE), 3 had secondary monosymptomatic nocturnal enuresis (SMNE) and 17 had non-mono­symptomatic nocturnal enuresis (NMNE). Demographic and NE-related details were assessed from electron­ic medical records and by telephone interview at the times 3, 6, 12 months and 3, 5, 10 years after the first examination. Sixty-seven of 95 patients were enrolled, of whom 57 had PMNE (M:F ratio 39:18, mean age 9.35 ± 2.81 years, mean age at improvement 11.5 ± 4.08 years), 8 had NMNE (M:F ratio 4:4, mean age 10.1 ± 2.64 years, mean age at improvement 12.6 ± 1.68 years) and 2 had SMNE (M:F ratio 1:1, mean age 12 years, mean age at improvement 13.5 ± 2.12 years).. The mean duration of follow up was 7.2 ± 2.5 years. All of the 67 children had 5 years follow up. Only 29 of 67 patients (19 with PMNE, 8 with NMNE and 2 with SMNE) had 10 years follow up and 4 of 19 with PMNE were still affected by NE. Out of 57 patients with PMNE 12 (2/12 with language disorders, 1/12 varicocele and 1/12 cryptorchidism) and out of 8 patients with NMNE 1 were still enuretic while all patients with SMNE were in remission.. We observed that language disorders and testicular pathology in NE children could be comor­bidities associated with persistence of NE and treatment resistance.

Topics: Adolescent; Antidiuretic Agents; Child; Chronic Disease; Comorbidity; Cryptorchidism; Deamino Arginine Vasopressin; Female; Follow-Up Studies; Functional Laterality; Humans; Language Disorders; Male; Nocturnal Enuresis; Remission Induction; Remission, Spontaneous; Time Factors; Varicocele; Young Adult

Bed wetting or nocturnal enuresis is a common problem among children. It is either monosymptomatic or may be associated with a voiding disorder. Many factors may contribute towards enuresis such as developmental delay, heredity, inappropriate nocturnal anti diuretic hormone secretion and reduced bladder capacity. Any child presenting with bed-wetting should be evaluated for any underlying bladder dysfunction before labeling as monosymptomatic enuresis. The evaluation consists of structured bowel and bladder history, detailed clinical examination, frequency volume record and appropriate investigations. The frequency volume diary is an indispensible component of evaluation and helps in establishing diagnosis and tailoring therapy. The treatment of monosymptomatic enuresis consists of positive psychological support, alarms and medication (desmopressin/ anticholinergics/ imiprammine). Children with features of underlying bladder dysfunction, anatomical anomalies and neurological disorders should be referred to a pediatrician without delay. The outcome of therapy is usually rewarding but varies, depending on the underlying etiology, motivation, compliance and family support. The cure rates with alarms are better than with desmopressin in monosymptomatic enuresis. Timely and appropriate therapy yields better outcomes. Thus, a thorough, scientific and evidence based approach is essential in children presenting with bed-wetting.

Topics: Adolescent; Algorithms; Behavior Therapy; Child; Child, Preschool; Cholinergic Antagonists; Deamino Arginine Vasopressin; Diagnosis, Differential; Female; Humans; Imipramine; Male; Nocturnal Enuresis; Referral and Consultation; Social Support; Urination Disorders

To evaluate treatment effectiveness for children with enuresis, according to the definitions of the International Children's Continence Society (ICCS, 2006).. Children ≥6 years of age followed a 4-month outpatient treatment consisted of a visit during which history regarding enuresis was taken, causes were explained and therapeutic tips & tricks were discussed. All children received a booklet about enuresis and were trained with an alarm and/or pharmacological therapy. At baseline, 4, 10 and 16 months, the number of wet nights during the previous 28 days and the use of medication were assessed. Success of treatment was determined using ICCS definitions of treatment outcome.. 66 children with enuresis were included (48 boys/18 girls) in this retrospective study. Mean age: 11(± 2.6) years. 91%(n = 60) of the children had non-monosymptomatic enuresis. Results at 4 months: 46% full, 15% good, 21% partial response (n = 66). At 10 months: 55% full, 4% good, 29% partial response (n = 49). At 16 months: 53% full, 6% good, 25% partial response (n = 34). Overall, use of pharmacological therapy showed a decline in time.. According to the ICCS definitions, outpatient treatment for enuresis shows a good overall treatment response, and these results can be used to compare with other studies in the future.

Topics: Adolescent; Antidiuretic Agents; Child; Clinical Alarms; Deamino Arginine Vasopressin; Female; Humans; Male; Nocturnal Enuresis; Outpatients; Pamphlets; Patient Education as Topic; Retrospective Studies; Tertiary Care Centers; Treatment Outcome; Young Adult

Previous reports have suggested that the incidence of spina bifida occulta in patients with nocturnal enuresis is higher than in the general population. However, the effect of spina bifida occulta on the response to nocturnal enuresis treatment is controversial. The purpose of this study was to investigate the relationship between spina bifida occulta and response to treatment of nocturnal enuresis.. Between 2006 and 2009, the records of 160 children with nocturnal enuresis were reviewed. Children with other organic urological disease or symptoms suggestive of spinal dysraphism were excluded. Plain radiography for the kidney-ureter-bladder was carried out before the start of the nocturnal enuresis treatment. Response to treatment of children with and without spina bifida occulta was compared.. Of 160 children, 53 were girls; the mean age was 7.8 ± 2.06 years. The mean duration of treatment was 8.7 ± 9.29 months. Spina bifida occulta was detected in 43 children (26.9%). Spina bifida occulta affected L4 in four children, L5 in 12 children, S1 in 26 children and S2 in one child. There was a significant difference between the spina bifida occulta and non-spina bifida occulta groups in terms of outcome (P=0.002), with a complete response more likely in children without spina bifida occulta (P=0.005). None of the children with primary non-mono symptomatic nocturnal enuresis and spina bifida occulta showed a complete response.. The presence of spina bifida occulta significantly affects the response to treatment in patients with nocturnal enuresis. Thus, verifying spina bifida occulta in this patient population can facilitate the prediction of the response to nocturnal enuresis treatment.

Topics: Adolescent; Antidiuretic Agents; Child; Child, Preschool; Cholinergic Antagonists; Deamino Arginine Vasopressin; Female; Humans; Incidence; Male; Nocturnal Enuresis; Predictive Value of Tests; Radiography; Retrospective Studies; Spina Bifida Occulta; Treatment Outcome

Topics: Deamino Arginine Vasopressin; Female; Humans; Male; Nocturnal Enuresis; Spina Bifida Occulta

To investigate why not all children with monosymptomatic nocturnal enuresis (MNE) treated with desmopressin give an adequate response.. We included 114 children with MNE aged 5-15 years (9.8 ± 0.2 years) who experienced at least 1 wet night and more than 2 dry nights during desmopressin treatment. The patients made home recordings for 2 weeks as baseline and for 2-4 weeks of desmopressin titration. Nocturnal urine production during wet and dry nights, and maximum voided volumes (MVVs) were documented in all patients.. Sixty-four patients were desmopressin non-responders, 29 were either partial responders or responders, while 21 patients were full responders. Desmopressin reduced nocturnal urine production dramatically during dry nights compared with pre-treatment wet nights. Nocturnal urine production during desmopressin treatment was significantly greater during wet nights compared to dry nights (243 ± 9.32 vs 176 ± 5.31 ml, P < 0.001). There was a highly significant correlation between individual nocturnal urine output and MVV, and dry nights were characterized by nocturnal urine output/MVV ratios well below 1.0.. The anti-enuretic response to desmopressin seems to be dependent upon the degree of reduction in nocturnal urine production. Research on desmopressin bioavailability in children is needed.

Topics: Adolescent; Antidiuretic Agents; Biological Availability; Child; Child, Preschool; Circadian Rhythm; Deamino Arginine Vasopressin; Drug Tolerance; Female; Follow-Up Studies; Humans; Male; Nocturnal Enuresis; Retrospective Studies; Treatment Outcome; Urination

Decreased nocturnal antidiuretic hormone (ADH) excretion has been suggested to be a causative factor for PNE in children. We investigate the demographic characteristics and nocturnal ADH levels of children with PNE who attended a tertiary referral center and to determine their response to treatment with desamino-D-arginine vasopressin (DDAVP).. We performed a retrospective study in 90 PNE children aged 6-12 years. We recorded the gender, height, weight, number of children per family, and psychosocial problems and compared these findings with the corresponding data obtained from a national survey. We also measured the nocturnal ADH levels and evaluated the response rate to DDAVP.. The number of PNE patients decreased with an increase in age. Enuresis was significantly associated with male gender (P = 0.044) and more number of children per family (P = 0.043). The rates of comorbidity with defecation problems, obesity, attention-deficit hyperactivity disorder (ADHD), and overweight were 36.7, 17.8, 12.2, and 10%, respectively. Although the prevalence of obesity and ADHD was higher among children with PNE, there was no significant difference between PNE patients and their prevalence in the community. The ADH levels at 2 a.m. and 8 a.m. were 0.87 ± 0.75 and 0.89 ± 0.76 pg/ml, respectively. In the 50 (55.5%) patients who received DDAVP treatment, the complete- and partial response rates were 86 and 14%, respectively.. Our data confirmed that PNE was predominant in boys and larger family, and similar to the findings for disease prevalence, the number of children seeking treatment tended to decrease with increasing age. Low ADH levels were recognized as a possible cause of PNE, thereby explaining the good response to DDAVP treatment in Taiwanese children with PNE.

Topics: Age Factors; Antidiuretic Agents; Child; Deamino Arginine Vasopressin; Family Characteristics; Female; Humans; Male; Nocturnal Enuresis; Osmolar Concentration; Retrospective Studies; Sex Characteristics; Taiwan; Treatment Outcome; Vasopressins

Topics: Antidiuretic Agents; Deamino Arginine Vasopressin; Female; Humans; Male; Nocturnal Enuresis

We evaluated bladder reservoir function in children with monosymptomatic nocturnal enuresis with and without response to desmopressin, and assessed the importance of first morning voiding when defining maximum voided volume.. A total of 238 patients 5 to 15 years old with monosymptomatic nocturnal enuresis completed 2 weeks of enuresis recordings and 4 days of frequency-volume charts. Of the patients 186 completed subsequent home recordings during titration with desmopressin. Maximum voided volumes with and without the first morning void were calculated. Desmopressin response was defined as greater than 50% reduction in wet nights. Maximum voided volume with and without first morning voiding was evaluated as a prognostic factor for desmopressin response.. Mean ± SD maximum voided volume without first morning void was comparable between desmopressin responders and nonresponders (230.5 ± 69.3 ml and 219.0 ± 84.8 ml, respectively, p = 0.391). Inclusion of the first morning void demonstrated responders to have significantly larger values than nonresponders (mean ± SD 296.0 ± 94.0 ml vs 233.5 ± 90.0 ml, p <0.001). When first morning void was included, desmopressin response was seen in 40% of patients with voided volumes of 65% expected volume for age vs 10% of patients with volumes less than 65% expected volume for age.. Maximum voided volume can be used as a predictor of desmopressin response only if first morning voids are taken into consideration. All patients with monosymptomatic nocturnal enuresis should receive clear instructions to include this measure when completing frequency-volume charts.

Topics: Adolescent; Antidiuretic Agents; Child; Child, Preschool; Deamino Arginine Vasopressin; Female; Humans; Male; Nocturnal Enuresis; Treatment Outcome; Urination

Despite the high prevalence of enuresis, the professional training of doctors in the evaluation and management of this condition is often minimal and/or inconsistent. Therefore, patient care is neither optimal nor efficient, which can have a profound impact on affected children and their families. Once comprehensive history taking and evaluation has eliminated daytime symptoms or comorbidities, monosymptomatic enuresis can be managed efficaciously in the majority of patients. Non-monosymptomatic enuresis is often a more complex condition; these patients may benefit from referral to specialty care centers. We outline two alternative strategies to determine the most appropriate course of care. The first is a basic assessment covering only the essential components of diagnostic investigation which can be carried out in one office visit. The second strategy includes several additional evaluations including completion of a voiding diary, which requires extra time during the initial consultation and two office visits before treatment or specialty referral is provided. This should yield greater success than first-line treatment.. This guideline, endorsed by major international pediatric urology and nephrology societies, aims to equip a general pediatric practice in both primary and secondary care with simple yet comprehensive guidelines and practical tools (i.e., checklists, diary templates, and quick-reference flowcharts) for complete evaluation and successful treatment of enuresis.

Topics: Antidiuretic Agents; Child; Clinical Alarms; Constipation; Deamino Arginine Vasopressin; Humans; Medical History Taking; Nocturnal Enuresis; Patient Compliance; Physical Examination

We evaluated the acute effect of indomethacin on renal water and solute handling in children with coexisting monosymptomatic nocturnal enuresis and desmopressin resistant nocturnal polyuria, and in healthy controls.. A total of 23 subjects were recruited, consisting of 12 children with monosymptomatic nocturnal enuresis and nocturnal polyuria with partial or no response to desmopressin, and 11 age matched controls. Children completed a 48-hour inpatient study protocol consisting of fractional urine collections and blood samples. Sodium and water intake were standardized. During the second night a dose of 50 mg indomethacin was administered orally before bedtime. Diuresis, urine osmolalities, clearances and fractional excretions were calculated for sodium, potassium, urea, osmoles and solute-free water. Renin, angiotensin II, aldosterone and atrial natriuretic peptide were measured in plasma. Prostaglandin E(2) was measured in urine.. Indomethacin markedly decreased the nocturnal sodium, urea and osmotic excretion in children with enuresis and controls. The overall effect on nocturnal urine output was inconsistent in the group with enuresis. Subjects in whom nocturnal diuresis was decreased following administration of indomethacin remained dry.. Prostaglandin inhibition leads to antidiuresis, reducing the amount of sodium, urea and osmotic excretion in children with monosymptomatic nocturnal enuresis and desmopressin resistant nocturnal polyuria. The sodium regulating hormones do not seem to mediate these processes. The overall effect in desmopressin nonresponders with nocturnal polyuria is variable. The extent to which indomethacin can be applied in the treatment of enuresis needs further evaluation.

Topics: Adolescent; Antidiuretic Agents; Child; Cyclooxygenase Inhibitors; Deamino Arginine Vasopressin; Drug Resistance; Humans; Indomethacin; Nocturnal Enuresis; Polyuria

The indication for the treatment of primary nocturnal enuresis was removed from all intranasal preparations of desmopressin in May 2007. Objective of this study was to examine whether and how fast this regulatory decision changed prescribing in affected children.. We analyzed claims data of the Gmünder ErsatzKasse (GEK) over the years 2004-2008. All children and adolescents aged 0-18 years who received at least one out-patient diagnosis of urinary incontinence in the corresponding years were included. Our outcome of interest was the proportion of oral desmopressin and its change over time.. A total of 6308 to 7207 children with a mean age of about 8 years were included annually (62-63% were male) and 14 746 packages of desmopressin were analysed (49.9% intranasal; 50.1% oral; 0.01% parenteral preparations). The proportion of patients using desmopressin decreased slightly from 13.9% in 2004 to 12.6% in 2008 ( p for trend = 0.0131). Between January 2004 (39.1%) and December 2006 (41.3%), the proportion of oral forms was nearly constant and doubled after that within a few months to about 80%.. Immediately after the removal of the indication for intranasal desmopressin, an increased prescribing of tablet forms in affected children was found in Germany.

Topics: Administration, Intranasal; Administration, Oral; Adolescent; Antidiuretic Agents; Child; Child, Preschool; Deamino Arginine Vasopressin; Female; Germany; Humans; Infant; Male; Nocturnal Enuresis; Off-Label Use; Practice Patterns, Physicians'; Urinary Incontinence

Desmopressin is a standard treatment for monosymptomatic nocturnal enuresis. Different formulations are promoted as bioequivalent, although these claims are not supported by comparative pharmacodynamic data in children. Food interaction is known to influence the bioavailability of desmopressin. We compared the pharmacodynamics of the 2 most frequently used desmopressin formulations, tablet and lyophilizate, with a standardized meal, allowing extrapolation to clinical reality, where the interval between evening meal and medication intake is limited for school-age children. We hypothesized there would be a faster pharmacodynamic response, and greater concentrating and antidiuretic activity for the fast dissolving (melt) formulation compared to the tablet with simultaneous food intake.. Two tests were performed on separate days in identical standardized conditions, starting with a 15 ml/kg water load. After achieving maximal diluting capacity a standardized meal was administered, followed by desmopressin tablet (t test) or melt (M-test). Diuresis rate and urinary osmolality were measured hourly. Paired data from 4 girls and 15 boys with a mean age of 12.1 years were obtained.. In the early response phase more than 25% of patients had a higher diuresis rate with tablet vs melt formulation, reaching statistical significance in the plateau phase (urine collected at hours 3 to 5, p <0.02) and in duration of action (urine collected at hours 5 to 8, p <0.005). For desmopressin melt smaller standard deviations in diuresis rate were remarkable. Concentrating capacity demonstrated no significant differences between formulations in the early response phase, in contrast to the plateau phase (p <0.036) and duration of action (p <0.001).. With meal combination desmopressin melt formulation has a superior pharmacodynamic profile to tablet, making it more suitable for the younger age group with a limited interval between meal and drug administration.

Topics: Antidiuretic Agents; Chemistry, Pharmaceutical; Child; Deamino Arginine Vasopressin; Female; Food-Drug Interactions; Humans; Male; Nocturnal Enuresis; Tablets; Therapeutic Equivalency

Topics: Antidiuretic Agents; Child; Deamino Arginine Vasopressin; Humans; Nocturnal Enuresis

Topics: Adolescent; Age Factors; Antidiuretic Agents; Child; Child, Preschool; Deamino Arginine Vasopressin; Family Therapy; Female; General Practice; Humans; Male; Nocturnal Enuresis; Patient Education as Topic; Practice Guidelines as Topic

Nocturnal enuresis is defined as involuntary wetting while asleep at least twice a week in children over the age of five. Primary nocturnal enuresis describes those children who have always been wet. Secondary nocturnal enuresis is defined as a relapse after a child has been completely dry for at least six months. Up to the age of nine years, nocturnal enuresis is twice as common in boys than girls but thereafter there is no sex difference in prevalence. At the age of five, 2% of children wet every night, and 1% are still wetting every night in their late teens. Bedwetting is not primarily caused by an underlying psychological disorder However, psychological problems and life events can exacerbate or precipitate bedwetting in susceptible children who have a genetic basis for their condition. The three systems approach to the management of the condition addresses: poor arousal from sleep, nocturnal polyuria and bladder dysfunction. Bedwetting is occasionally caused by underlying medical conditions; primarily urological, neurological, or metabolic. It can also be associated with obstructive sleep apnoea. However, these causes are uncommon in primary enuresis. A basic history and examination should exclude these conditions. If the bedwetting has started in the past few days or weeks, systemic illness should be considered e.g. UTI, diabetes mellitus. With secondary enuresis, symptoms or signs of medical and psychological conditions or life events may be elicited as possible causes, and may need separate treatment. Alarm treatment should be considered in any child over seven. The alarm takes several weeks to be effective and needs commitment from both child and carers. Desmopressin may be used as first-line treatment if rapid onset and/or short-term improvement is the priority of treatment or an alarm is inappropriate or undesirable.

Topics: Antidiuretic Agents; Deamino Arginine Vasopressin; Drinking; Female; Humans; Male; Nocturnal Enuresis; Primary Health Care; Urinary Bladder

Hypercalciuria may present with dysuria, urinary incontinence and nocturnal enuresis (NE). To determine the frequency of hypercalciuria in NE patients and normally continent children, we studied 122 consecutive pre- school children with NE referred to our nephrology clinic during two years, from September 2007 to August 2009. We measured the 24- hour urinary calcium. Furthermore, we compared the response to nasal desmopressin in hypercalciuric and normocalciuric patients. Hypercalciuria was found in 26 (21.3 %) of the NE patients as compared with five (4.5%) of 110 continent children [(P < 0.001), OR = 5.68 (95% CI, 2.1-15.4)]. In addition, the mean 24- hour urine calcium/body weight ratio (24h- U- Ca/Bw) was higher in NE patients, 3.04 ± 1.54 vs. 2.57 ± 0.9, respectively (P = 0.005). Wet nights per week in both NE patients with and without hypercalciuria at the first visit ranged from two to seven (median: 6 and 7, respectively), and the mean overall success rate of the nasal desmopressin therapy was 83.3% and 90%, respectively (P > 0.05). The response to desmopressin above 90% occurred within one month of therapy without a significant change in the levels of hypercalciuria. We conclude that these results suggest that hypercalciuria has a significant association with NE and does not interfere with the desmopressin therapy.

Topics: Administration, Intranasal; Antidiuretic Agents; Case-Control Studies; Child; Comorbidity; Deamino Arginine Vasopressin; Female; Humans; Hypercalciuria; Male; Nocturnal Enuresis

It has recently became apparent that severe primary monosymptomatic nocturnal enuresis (MNE) has a worse prognosis than generally believed, and may have major consequences on the well-being of the child, thus making treatment mandatory. Desmopressin is one of the most widely prescribed medications for MNE, and in this current opinion article we discuss the safety of desmopressin in children with this condition. Following a US FDA request in December 2007 that the prescribing information for desmopressin nasal spray be updated, desmopressin spray is no longer indicated for the treatment of MNE or for use in patients at risk for hyponatraemia. Multiple reports of hyponatraemia in patients with nocturia (mainly the elderly) led to an increased awareness of the risks associated with desmopressin. While the pathogenesis of hyponatraemia in those over 65 years of age relates more to changing renal water and solute handling, we believe that in the young, overdosing and insufficient fluid restriction are usually the major causes. Hyponatraemia is most frequently reported when desmopressin is administered by nasal spray compared with the tablet formulation. This may simply reflect the fact that for more than 10 years the spray was the only available mode of administration in many countries. However, it may also reflect the higher biodisponibility and/or intraindividual variability of pharmacokinetics of the spray compared with the tablet. There are few serious adverse events reported for the melt formulation (oral lyophilisate), but as it has only recently become available on the market, it would be premature to conclude that it has a better safety profile. We believe that desmopressin in all formulations has a good safety profile in children with MNE, provided that treatment is properly prescribed and monitored; improving the training of doctors and patients in the dose-response kinetics of the drug, teaching appropriate restriction of fluid intake and by encouraging the use of desmopressin within a narrow dose range (10-20 microg spray, 120-240 microg melt and 200-400 microg tablet) when used in primary-care settings. Titrating higher doses in therapy-resistant patients should probably be carried out in a specialized enuresis centre, and only after documenting adequate morning urinary diluting capacity. In summary, the risk of hyponatraemia is exacerbated by misuse of the drug rather than an inherent danger associated with the drug, which in our opinion should b

Topics: Administration, Intranasal; Administration, Oral; Aged; Antidiuretic Agents; Child; Deamino Arginine Vasopressin; Dose-Response Relationship, Drug; Humans; Hyponatremia; Nocturnal Enuresis; Risk Factors

Dilutional hyponatremia, although not uncommon, is an underestimated problem in the pediatric population. In most cases, it results from excessive hydration or water retention, also described as the so-called water intoxication. One of the most known causes is the use of desmopressin in enuretic children. This drug enhances the free water reabsorption in the renal collecting ducts. The addition of the anticholinergic agent oxybutynin aggravated the condition by causing a dry mouth with excessive thirst and water intake in our first case. Dietary water overconsumption, either voluntary or involuntary, is a phenomenon seen in formula-fed babies. But in our second case, a game involving forced ingestion of large amounts of water had serious consequences including hyponatremia-related coma. An effort should therefore be made to inform caretakers about the risks of these games. These cases, provoked by rather unusual and peculiar causes, illustrate again that electrolytes and especially serum [Na(+)] are key points to be determined in a child with diminished consciousness. Moreover, an accurate history including the intake of medication and dietary information should be made.

Topics: Antidiuretic Agents; Child; Cholinergic Antagonists; Deamino Arginine Vasopressin; Drug Therapy, Combination; Electrocardiography; Female; Humans; Hyponatremia; Male; Mandelic Acids; Nocturnal Enuresis; Water Intoxication

Topics: Antidiuretic Agents; Behavior Therapy; Child; Counseling; Deamino Arginine Vasopressin; Humans; Nocturnal Enuresis; Patient Education as Topic; Recurrence

Bedwetting (nocturnal enuresis) is a common and distressing condition, both for children and young people and their families, and the National Institute for Health and Clinical Excellence (NICE) has produced its first guidelines for its assessment and treatment in those aged up to 19 years. This paper, by two NICE guideline development group members, provides an update on the new guidance. Treatment options include the provision of advice, use of a reward system and/or alarm, and desmopressin medication. These should be considered carefully depending on individual needs. Treatment for most children is effective and successful. Where necessary, referrals may be made to a specialist enuresis practitioner.

Topics: Adolescent; Algorithms; Antidiuretic Agents; Attitude to Health; Child; Child, Preschool; Deamino Arginine Vasopressin; Decision Trees; Drinking Behavior; Female; Humans; Male; Medical History Taking; Nocturnal Enuresis; Nursing Assessment; Patient Care Planning; Patient Education as Topic; Practice Guidelines as Topic; Psychology, Child; Reward; Self Concept

Topics: Antidiuretic Agents; Deamino Arginine Vasopressin; Humans; Nocturnal Enuresis; Water Intoxication

Topics: Antidiuretic Agents; Behavior Therapy; Deamino Arginine Vasopressin; Female; Humans; Male; Nocturnal Enuresis

Desmopressin is an evidence-based medicine level I, category A therapy for monosymptomatic nocturnal enuresis. However, in up to 40% of patients only partial desmopressin response is obtained. While the poor pharmacokinetic characteristics of the different available formulations may have a role in apparent therapy resistance, there are limited data available to support this theory. We sought to identify pharmacodynamic factors involved in partial desmopressin response or desmopressin resistance in children with monosymptomatic nocturnal enuresis, with special emphasis on concentrating performance, and time to reach and duration of maximal urine concentration.. We evaluated 64 children with monosymptomatic nocturnal enuresis and proved nocturnal polyuria lacking full response to desmopressin treatment. The study involved 2 separate home based test days (A and B), each consisting of 9 timed urine collections starting in the evening 1 hour before desmopressin administration and continuing for 16 hours following desmopressin administration. Test A was done during fluid restriction, and test B was done during an oral fluid load.. Under fluid restriction 16 patients failed to achieve urine concentration greater than 850 mOsmol/l at the midnight collection following desmopressin administration. After an oral fluid load given at the start of the test the majority of patients failed to reach maximal concentration of urine as voided during hydropenia, and 45 patients failed to regain appropriate dilution of urine even when an oral water load of 15 ml/kg (urine osmolality less than 750 mOsmol/l) was given in the morning at the end of the test. This finding is suggestive of a prolonged duration of action of the drug.. Pharmacodynamic tests reveal a suboptimal effect of desmopressin on urine concentration in a significant percentage of patients, which worsens when fluid is not restricted before desmopressin administration. Also the time to reach maximal antidiuretic effect and the duration of pharmacodynamic action show a wide range, requiring individualization of mode and time of administration. Our data demonstrate that a simple pharmacodynamic test as described may give important information on time of dosing, duration of action and influence of oral fluid intake, allowing individualization of therapy. Data also reveal that desmopressin should be administered at least 1 hour before bedtime, and that in case of therapy resistance a longer interval, up to 2 hours, might further reduce diuresis rate in the early night. Because of the documented prolonged action of desmopressin in some patients, increasing the dose without performing pharmacodynamic testing is no longer acceptable.

Topics: Administration, Intranasal; Adolescent; Antidiuretic Agents; Child; Deamino Arginine Vasopressin; Female; Humans; Male; Nebulizers and Vaporizers; Nocturnal Enuresis; Treatment Failure

To evaluate, in a prospective study, the combination of the antimuscarinic propiverine and the antidiuretic hormone-agonist desmopressin in children and adolescents not responsive to previous monotherapy, as in primary monosymptomatic enuresis (PME), combined treatments are considered a second-line approach after the failure of monotherapy.. The study included 122 children and adolescents (mean age 10.8 years, range 5-21) with PME and so far unresponsive to single or multiple monotherapy. Propiverine (body weight <30 kg, 15 mg/day; >or=30 kg, 20 mg/day) and desmopressin (0.4 mg/night) were administered over 3 months, followed by successive structured withdrawal programmes for propiverine and desmopressin, depending on the amount of loss of urine at night before treatment.. The re-evaluation of unresponsive patients, incorporating video-urodynamics, showed neurogenic detrusor overactivity, isolated detrusor sphincter dyssynergia and vesicorenal reflux in 12.3% (15/122) of patients, so far falsely treated as enuresis. In 107 of 122 patients the diagnosis of PME was confirmed. The primary efficacy outcome, continence at night, was achieved in 104 of 107 patients (97.2%). During the individual follow-up periods (3-12 months), 23 of 107 (21.5%) patients relapsed after withdrawal of both medications. Adverse events of moderate intensity were rare (3.7%).. Re-evaluation of patients after monotherapy has failed is justified, because other entities can be discovered in patients so far treated unsuccessfully for enuresis. The combination of propiverine and desmopressin is highly effective in children with PME. Our results support the case for further optimizing the inaugurated treatment algorithm of PME for treatment duration, dose-titration and structured withdrawal programmes, thus possibly further decreasing relapse rates.

Topics: Adolescent; Adult; Antidiuretic Agents; Benzilates; Child; Child, Preschool; Deamino Arginine Vasopressin; Drug Therapy, Combination; Humans; Muscarinic Antagonists; Nocturnal Enuresis; Prospective Studies; Secondary Prevention; Treatment Outcome; Young Adult

To investigate the factors affecting desmopressin response and relapse rates in an adult male population with monosymptomatic nocturnal enuresis (MNE). Nocturnal enuresis is a frequent heterogeneous condition, which is genetically complex in nature.. Between September 2007 and January 2009, a total of 143 male soldiers with nocturnal enuresis admitted to a military referral center. Eighty-six male soldiers with MNE were investigated. Family history, smoking habits, previous treatment history, coexisting urinary symptoms, bowel habits, maximal functional bladder capacity, and body mass index were examined to determine their effects on desmopressin response. All patients initially received 0.2 mg of desmopressin. Patients were evaluated after 2 weeks and non-full responders were switched to 0.4-mg desmopressin, with total treatment duration of 3 months. The mean follow-up after starting the initial dose was 9.4 months (4.5-15 months).. Of the 86 patients with MNE, 37 patients (43%) showed full response. None of the investigated parameters were shown to affect response rates. With regard to the relapse rates, 36.1% of the patients were taking 0.2-mg tablets and 63.9% were taking 0.4-mg tablets. This difference was statistically significant (P <.05). Other parameters did not have any significant effect on relapse rates.. Adult male MNE is a heterogeneous condition and desmopressin appears to be an effective and well-tolerated treatment. Higher response rate can be predicted if the nocturnal urine output exceeds functional bladder capacity for each individual. Our study also contributed that relapse rates depend on initial tailored dose; however, this needs to be confirmed with further studies.

Topics: Adult; Antidiuretic Agents; Deamino Arginine Vasopressin; Humans; Male; Nocturnal Enuresis; Prospective Studies; Recurrence; Treatment Outcome; Young Adult

Topics: Antidiuretic Agents; Child; Deamino Arginine Vasopressin; Humans; Nocturnal Enuresis

Topics: Antidiuretic Agents; Child; Deamino Arginine Vasopressin; Humans; Nocturnal Enuresis

In this national, multicenter, retrospective survey we tested whether structured withdrawal of desmopressin, in which dose frequency rather than dose quantity was gradually decreased, would improve outcome.. Enrolled in the study were 487 monosymptomatic enuretic patients from a total of 181 centers (The Enuresis Algorithm of Marschall Survey Group). At study outset 41% of patients had 7 wet nights per week, 45% had 3 to 6 and 14% had fewer than 3. All patients were treated with desmopressin, which was abruptly terminated or tapered with analogue by a structured scheme. Response rates were compared in the groups according to International Children's Continence Society guidelines.. The 173 children with abrupt termination had a 51% response rate, including a full and partial response in 44.1% and 27%, respectively, and no response in 22%. The 314 children with tapering had a 72% response rate, including a full and partial response in 66.8% and 24%, and no response in 4% (p <0.0001). Enuresis frequency with abrupt termination decreased from 21 wet nights per month before treatment to 6. The tapering group had 21 wet nights per months before and 2 after treatment (p <0.0001). Followup at 1 month showed fewer than 2 wet nights per month in 57% of cases with abrupt termination and in 80% with tapering (p <0.0001). Pretreatment had no influence. No severe side effects occurred.. This national, multicenter, retrospective analysis proves that antidiuretic treatment followed by a structured withdrawal program is superior to regular treatment with abrupt termination in enuretic children. Hence, desmopressin followed by structured withdrawal should be the standard. It is also superior to published outcomes of alarm treatment.

Topics: Adolescent; Adult; Antidiuretic Agents; Child; Child, Preschool; Clinical Protocols; Deamino Arginine Vasopressin; Female; Humans; Male; Nocturnal Enuresis; Retrospective Studies; Treatment Outcome; Young Adult

Studies of desmopressin in children with primary nocturnal enuresis show a greater than 90% decrease in wet nights in 20% to 30%, a 50% to less than 90% decrease in 20% to 40% and less than a 50% decrease in up to 60%. Insufficient response to desmopressin is attributable to various factors, including differences in the primary nocturnal enuresis definition, underlying bladder dysfunction and/or desmopressin pharmacokinetic characteristics. However, little attention has been given to poor compliance with therapy as a possible explanatory factor. For a drug with an effect duration limited to the night after administration a high degree of compliance is essential to ensure consistent therapeutic effects.. This was a substudy of an international investigation of treatment for 6 months or less with desmopressin tablets in children with primary nocturnal enuresis. Medication was dispensed at each visit as required and collected at each subsequent visit. Compliance was determined by pill counts by study staff.. Compliance data were available on 723 patients. Of the patients 81% to 91% ingested all medication as instructed during the initial run-in phases. However, this decreased to 77% and 71% during the first and second 3-month treatment periods, respectively.. Patient motivation and compliance are generally stronger in clinical trials than in clinical practice. However, this study shows that some patients were poorly compliant with medication even at study initiation and only 71% were fully compliant with long-term treatment. Decreased compliance was associated with a lower response rate. Patients should be encouraged to comply fully with treatment to achieve an optimal outcome.

Topics: Adolescent; Antidiuretic Agents; Child; Child, Preschool; Deamino Arginine Vasopressin; Female; Humans; Male; Nocturnal Enuresis; Patient Compliance; Treatment Outcome

We sought to evaluate the effect of desmopressin on renal water and solute handling in children with monosymptomatic nocturnal enuresis and desmopressin resistant nocturnal polyuria compared to healthy controls.. A total of 12 patients with enuresis and nocturnal polyuria, normal bladder reservoir function and no response to desmopressin, and 10 age matched controls were enrolled in the study. Children were admitted to the hospital for a 48-hour protocol comprising urine collections and blood sampling. Sodium and water intake was standardized. During the second night children received 40 mug intranasal desmopressin. Parameters characterizing the renal water and solute handling were measured and compared between baseline nights and nights with desmopressin.. Desmopressin markedly reduced nocturnal urine output in patients with enuresis, minimizing sodium, urea and overall solute excretion, despite the fact that these children were unresponsive to desmopressin at home. This effect on renal sodium handling was not mediated by atrial natriuretic peptide, angiotensin II, aldosterone or renin. Desmopressin did not influence urinary prostaglandin E(2) excretion. The antinatriuretic effect was seen only in patients with enuresis, and it was directly correlated with the reduction in urine output.. Children with nocturnal enuresis and nocturnal polyuria who do not exhibit adequate response to desmopressin at home seem to respond well to the agent at the clinic. The effect of desmopressin in children with enuresis seems largely dependent on reductions in the amount of sodium excreted. Sodium regulating hormones remained unaffected by desmopressin, indicating a possible direct effect of the agent on renal sodium handling.

Topics: Adolescent; Analysis of Variance; Antidiuretic Agents; Case-Control Studies; Child; Deamino Arginine Vasopressin; Diuresis; Drug Resistance; Follow-Up Studies; Humans; Kidney Function Tests; Natriuresis; Nocturnal Enuresis; Osmolar Concentration; Polyuria; Probability; Prostaglandins; Reference Values; Severity of Illness Index; Treatment Outcome; Urodynamics; Water-Electrolyte Balance

To identify phenotypic characteristics in three large families with autosomal dominant nocturnal enuresis (NE), and to elucidate whether such characteristics persist after cessation of symptoms.. From three unrelated NE kindreds (A-C) we included 98 living members of whom 34 either had active NE (>one wet night/month after the age of 5 years) or a history of NE. The family members were interviewed to identify NE type and severity. Subsequently, night-time urine production was recorded for 2 weeks at home and 4 days of frequency-volume charts were completed.. There was coexistence of both primary and secondary NE (family A), coexistence of monosymptomatic NE and incontinence (families A and C), pure monosymptomatic NE (family B) and pure day-time incontinence (family C). However, the NE phenotype of family A was characterized by nocturnal polyuria and normal bladder capacity, whereas family C was characterized by normal nocturnal urine production and reduced bladder capacity. Interestingly, there were no differences between former affected and unaffected family members in any of the families for night-time urine production, nocturia frequency, nocturia volumes, day-to-night ratios, or bladder capacity.. The clinical phenotype in three large families with hereditary severe NE was heterogeneous within and between families. However, the NE phenotype seemed to differ between two of the families for nocturnal urine production, bladder capacity, and response to desmopressin. These results indicate that the genes responsible for NE in these families are not related directly to the presence of primary vs secondary NE or coexisting day-time problems. However, there might be genetically determined differences in bladder capacity and/or nocturnal urine production.

Topics: Adolescent; Adult; Antidiuretic Agents; Child; Deamino Arginine Vasopressin; Female; Humans; Male; Middle Aged; Nocturnal Enuresis; Pedigree; Penetrance; Phenotype; Urodynamics

To evaluate the long-term success of the enuretic alarm device in patients with monosymptomatic primary nocturnal enuresis.. Sixty-two patients who had significant monosymptomatic primary nocturnal enuresis were included. They used an enuretic alarm for 3 months. At the end of the treatment, 15 of the patients did not have benefit from the enuretic alarm. Overall, 47 patients benefited from the enuretic alarm. The long-term follow-up was conducted prospectively.. The mean age was 9.3 (range 5-16) years and mean follow-up time was 19.2 (range 12-30) months. In the follow-up period, relapse was observed in 46.8% (n = 22/47) of these patients. Twenty-two patients reused the enuretic alarm device for 3 months after relapse occurrence and 13 patients (59%) recovered. Although re-relapse was observed in seven of them in the 6 months, six patients had a full response. In total, 65.9% of the patients (n = 31/47) maintained a full response after enuretic alarm treatment in the long-term follow-up. Thirty-one of the 62 patients underwent combination treatment (enuretic alarm plus medical therapy) for unsuccessful enuretic alarm treatment. The overall full response rate for combination treatment was 16.1%.. In the long-term follow-up, the enuretic alarm device provided an acceptable full response rate in patients with primary nocturnal enuresis.

Topics: Adolescent; Behavior Therapy; Child; Child, Preschool; Combined Modality Therapy; Deamino Arginine Vasopressin; Female; Follow-Up Studies; Humans; Imipramine; Male; Nocturnal Enuresis; Prospective Studies; Recurrence; Retreatment; Treatment Outcome

This study examined the sustainability of remission of primary nocturnal enuresis (PNE) using an algorithm-based multimodal treatment plan, Try for Dry. Remission of PNE using the Try for Dry treatment method was retained longer and more often than using a non-Try for Dry plan.

Topics: Adolescent; Algorithms; Antidiuretic Agents; Child; Combined Modality Therapy; Constipation; Deamino Arginine Vasopressin; Drug Administration Schedule; Drug Therapy, Combination; Equipment Failure; Humans; Incidence; Kaplan-Meier Estimate; Mandelic Acids; Muscarinic Antagonists; Nocturnal Enuresis; Nursing Evaluation Research; Patient Care Planning; Remission Induction; Retrospective Studies; Surveys and Questionnaires; Toilet Training; Treatment Outcome; Urodynamics

The reason for our search was various investigations about urinary tract dysfunctions in enuretic children.. The aim of our study was estimation of lover urinary tract function in children with monosymptomatic primary nocturnal enuresis without positive reaction for a long non pharmacological therapy.. 54 children after 9-12 months behavioral therapy and short pharmacological treatment (desmopresin) was undergoing urodynamic investigation (uroflowmetry and cystometry).. Urodynamic disorders was found in 44/54 of estimated children. In 34 of children it was overactive bladder, in 6 patients we found detrusor-sphincter discoordination. Five children had decreased bladder capacity. Next to non pharmacological treatment we used anticholinergic or Baclofen depending on the results of urodynamic tests. The response to the treatment (non bedwetting at all) we observed in 34 children (in 9 of them after 3 months of therapy, in 16 after 6 months of therapy and in 12 after 12 months of therapy). The rest of children had decreased number of wet night per month.. The pharmacological treatment of urodynamic disorders helps to children with monosymptomatic primary nocturnal enuresis to lost this symptom.

Topics: Antidiuretic Agents; Baclofen; Child; Cholinergic Antagonists; Deamino Arginine Vasopressin; Female; Humans; Male; Nocturnal Enuresis; Treatment Outcome; Urodynamics; Urologic Diseases

In this issue Ferrara et al. present an important placebo-controlled, three-arm, double-blind, double-dummy, study on the treatment of nocturnal enuresis, demonstrating that homotoxicology is superior to placebo but less effective than desmopressin. Nocturnal enuresis is a disease with a heterogeneous aetiology and complex pathophysiology. The fact that different therapies may result in a wide range of responses is, therefore, not surprising. Differences in success rate can, therefore, be largely attributed to selection bias in the sub-populations. This consideration must be taken into account for every study design, to avoid premature interpretation of the results. Positive results in a paper are only not subject for discussion if both methodology and study population fulfil the highest standards, because negative results are not likely to be reported. Several points of weakness are present in the majority of studies, such as (a) inappropriate subtyping of the patients (terminology) or (b) epidemiological data, (c) insufficient documentation of patients' characteristics, (d) lack of plausible explanation as to why the placebo effect might be absent, (e) the heterogeneity of the severity of bedwetting. All these may lead to false positive and/or false negative results. In this commentary we try to tackle these different issues which might be relevant for the interpretation even of placebo-controlled studies like that of Ferrara et al.

Topics: Antidiuretic Agents; Bias; Child; Clinical Protocols; Deamino Arginine Vasopressin; Double-Blind Method; Homeopathy; Humans; Nocturnal Enuresis; Placebos; Randomized Controlled Trials as Topic; Research Design; Toxicology

We sought to evaluate the combination of the enuresis alarm and desmopressin in treating children with enuresis.. A retrospective analysis was performed on data from 423 children treated at our clinics with the enuresis alarm during the years 2000 to 2004. Frequency volume charts and desmopressin titration facilitated characterization of the participants using the current International Children's Continence Society standardization. Children were treated with the enuresis alarm as monotherapy before the addition of desmopressin, which commenced after 6 weeks in patients exhibiting inadequate response to alarm or after 2 weeks in patients experiencing multiple enuretic episodes per night or showing no indication of improvement.. Of the initial population 315 children (74%) were treated only with alarm, of whom 290 became dry. A total of 108 children (26%) were treated with a combination of alarm and desmopressin, with 80 being cured. Children dry on alarm therapy were not different from those needing the addition of desmopressin in terms of demographics. Children dry on desmopressin plus alarm had higher average nocturnal urine production on wet nights (303 +/- 12 ml compared to 269 +/- 5 ml, p <0.001). Maximum voided volume before treatment corrected for age was not different between children dry on alarm and those dry on combination therapy (0.84 +/- 0.02 compared to 0.86 +/- 0.05, not significant).. Children needing the addition of desmopressin have a higher nocturnal urine production on wet nights but do not seem to differ in terms of bladder reservoir function characteristics.

Topics: Antidiuretic Agents; Behavior Therapy; Child; Combined Modality Therapy; Deamino Arginine Vasopressin; Female; Humans; Male; Nocturnal Enuresis; Retrospective Studies; Toilet Training

Topics: Antidepressive Agents; Antidiuretic Agents; Child; Cholinergic Antagonists; Combined Modality Therapy; Deamino Arginine Vasopressin; Diet Therapy; Humans; Nocturnal Enuresis; Prostaglandin Antagonists; Treatment Failure

We correlated the circadian rhythm of plasma arginine vasopressin and urine output profile to desmopressin response, presence or absence of an enuretic episode, and age and gender in children with nocturnal enuresis.. We studied 125 children 6 to 17 years old (mean age 10.4 +/- 3 years) with monosymptomatic nocturnal enuresis. Circadian inpatient studies were performed with standardized fluid intake, 7 blood sampling times and 6 urine collection periods. Subsequently, nocturnal urine volume was measured at home by diaper weighing for 4 weeks in 78 patients (2 weeks without treatment followed by 2 weeks of dose titration from 20 to 40 mug desmopressin at bedtime).. The circadian studies showed that all groups of patients had an attenuated arginine vasopressin rhythm, females generally had lower circadian plasma arginine vasopressin levels than males, desmopressin responders with enuresis during the study night had the largest nocturnal urine excretion rate and most pronounced arginine vasopressin deficiency, and nocturnal urine output was significantly greater during nights with enuresis than nights without. Part of this polyuria was caused by increased sodium excretion. The home recordings confirmed higher nocturnal urine volume on enuresis nights.. In addition to providing further pathophysiological support for the role of a nocturnal arginine vasopressin deficiency behind nocturnal polyuria in a subset of patients with enuresis, the results emphasize the clinical value of estimating nocturnal urine production on wet nights before selecting a therapeutic modality.

Topics: Adolescent; Antidiuretic Agents; Child; Circadian Rhythm; Deamino Arginine Vasopressin; Female; Humans; Male; Nocturnal Enuresis; Urine; Vasopressins

We evaluated pretreatment values of circadian rhythm of urine production and urine osmolality in children with different subtypes of monosymptomatic nocturnal enuresis, and investigated their predictive value for desmopressin response.. We assessed 125 consecutive patients with monosymptomatic nocturnal enuresis, nocturnal polyuria and normal functional bladder capacity who were treated with desmopressin for a median of 17 months (range 3 to 100). Patients were characterized according to the desmopressin response as full responders or nonfull responders. Baseline parameters were obtained from a 2-week home recording diary. Results were compared with 125 consecutive children with monosymptomatic nocturnal enuresis and reduced functional bladder capacity.. No differences in pretreatment values of functional bladder capacity, circadian rhythm of urine production or urine osmolality were found between desmopressin full responders and nonfull responders. Patients with nocturnal polyuria had a significantly higher 24-hour diuresis volume compared to children with reduced functional bladder capacity. Some children with reduced functional bladder capacity also had nocturnal polyuria.. Our findings show that the characteristics of nocturnal polyuria in patients with monosymptomatic nocturnal enuresis and normal functional bladder capacity do not predict desmopressin response. The wide overlap among the different subgroups suggests that dividing patients with monosymptomatic nocturnal enuresis into those with reduced functional bladder capacity and those with desmopressin responsive nocturnal polyuria might be insufficient. Patients with nocturnal polyuria and normal functional bladder capacity have a significantly higher daytime and nighttime diuresis volume compared to children with reduced functional bladder capacity, suggesting a direct correlation between daytime fluid intake and nocturnal diuresis rate. Some children with reduced functional bladder capacity also have nocturnal polyuria.

Topics: Adolescent; Antidiuretic Agents; Child; Circadian Rhythm; Cohort Studies; Compliance; Deamino Arginine Vasopressin; Female; Humans; Male; Nocturnal Enuresis; Osmolar Concentration; Polyuria; Predictive Value of Tests; Treatment Outcome; Urinary Bladder; Urine

Topics: Administration, Intranasal; Antidiuretic Agents; Deamino Arginine Vasopressin; Drinking; Half-Life; Humans; Hyponatremia; Nocturnal Enuresis

To report the outcomes and follow-up at 2 years of children with monosymptomatic nocturnal enuresis (MNE) managed in a private paediatric community practice utilising body-worn alarms and supportive programmes.. 522 consecutive children presenting with MNE were assessed and managed with a comprehensive supportive programme and body-worn alarm. Data were recorded prospectively and outcomes assessed at 6 and 24 months.. 505 proceeded with management. A total of 79.0% achieved initial dryness within a median of 10 weeks. Of those achieving initial dryness 73.0% had remained dry at 6-month follow-up and 64% had remained dry at 24 months. A total of 99.2% follow-up was achieved. Nineteen per cent of children required more than 16 weeks management with 56% achieving dryness. More girls achieved dryness than boys and in a shorter time. There was no gender difference in relapse rates at 6 and 24 months. No difference in achieving initial success was found with respect to initial severity of wetting, nor age. Relapse rates were unrelated to gender, age, or initial severity.. MNE can be successfully managed using body-worn alarms achieving good initial and long-term complete dryness, without the need for expensive pharmacologic intervention. A strong supportive programme can make the management less arduous for child and family.

Topics: Antidiuretic Agents; Child; Child, Preschool; Deamino Arginine Vasopressin; Evidence-Based Medicine; Female; Humans; Male; Nocturnal Enuresis; Outcome Assessment, Health Care; Pediatrics; Prospective Studies; Victoria

Primary nocturnal enuresis (PNE) is a common problem in childhood and adolescence. Although various treatments are highly effective, a common underlying hypothesis on the pathogenesis is lacking. The success of desmopressin, a synthetic analogue of the antidiuretic hormone vasopressin, has been attributed to increased renal water reabsorption that is mediated by activation of the renal vasopressin V2 receptor (V2R). However, this effect does not explain other symptoms of PNE, such as the failure to arouse upon bladder distension. This study identified a family in which one child displayed PNE and coexisting nephrogenic diabetes insipidus, as a result of a novel nonsense mutation in the V2R gene (C358X). Cell-biologic investigations revealed that V2R-C358X is retained in the endoplasmic reticulum and is unstable, which explains his nephrogenic diabetes insipidus. Consistently, extrarenal V2R-mediated responses were absent in the patient who was treated with desmopressin. Administration of desmopressin, however, changed his PNE into nocturia, because he now still voided unchanged high urinary volumes at night but woke up and went to the bathroom. Withdrawal of desmopressin was accompanied by bedwetting, whereas reintroduction again relieved the symptoms. Therefore, these data indicate that neither a functioning renal concentration system nor a functional V2R is needed for the therapeutic benefit of desmopressin in PNE. Rather, it suggests that another vasopressin receptor and other organ(s) is the target for desmopressin to relieve PNE.

Topics: Animals; Cells, Cultured; Child; Chlorocebus aethiops; COS Cells; Deamino Arginine Vasopressin; Diabetes Insipidus, Nephrogenic; Dogs; Humans; Kidney; Male; Mutation, Missense; Nocturnal Enuresis; Pedigree; Receptors, Vasopressin; Transfection

The anti-incontinence effect of desmopressin resides in its concentrating capacity and antidiuretic properties. We compared nighttime urine production on wet and dry nights in a highly selected study population of children with monosymptomatic nocturnal enuresis associated with proved nocturnal polyuria who responded only partially to intranasal desmopressin.. We retrospectively analyzed 39 home recordings of nocturnal urine production and maximum voided volume in children 7 to 19 years old (median 8.9) with monosymptomatic nocturnal enuresis with nocturnal polyuria who had a partial response to desmopressin. Nocturnal diuresis volume and maximum voided volume were documented at baseline (14 days) and during 3 months of followup.. Baseline nocturnal urine output (439 +/- 39 ml) was significantly higher than the maximum voided volume (346 +/- 93 ml, p <0.01). During desmopressin treatment nocturnal urine output on wet nights (405 +/- 113 ml) differed significantly from that on dry nights (241 +/- 45 ml). During treatment nocturnal urine output on wet nights did not differ from baseline values.. Persistence of nocturnal polyuria on wet nights in partial desmopressin responders may be related to an insufficient antidiuretic effect. In addition to poor compliance and suboptimal dosing, the poor bioavailability of intranasal desmopressin may be a pathogenic factor. Further prospective studies are needed.

Topics: Administration, Intranasal; Adolescent; Adult; Antidiuretic Agents; Child; Deamino Arginine Vasopressin; Female; Humans; Male; Nocturnal Enuresis; Polyuria; Urine

Obesity continues to be a leading public health concern in the United States. Our previous studies have suggested that there is a high rate of obesity in children with dysfunctional voiding, especially nocturnal enuresis. We investigated the correlation between body mass index and the efficacy of treatment in obese patients.. We evaluated retrospectively records from patients seen with a diagnosis of nocturnal enuresis or dysfunctional voiding between January 2004 and July 2005. Bladder and bowel symptoms and urinary diary data were evaluated, and body mass index percentile was determined. Response to treatment was evaluated and correlated with body mass index percentile.. We evaluated 250 children, of whom 96 (38%) had nocturnal enuresis and 154 (62%) had dysfunctional voiding. Body mass index was normal in about half of the patients, and half were above the 85th percentile for body mass index. Patients with a body mass index above the 85th percentile had a reduced response to therapy. After treatment patients with a normal body mass index had a lower nocturnal accident frequency than those above the 85th percentile. Similarly, in those with voiding dysfunction the response rate was 65% in association with a normal body mass index vs 35% with a high body mass index. Furthermore, patients with a normal body mass index had a significantly higher rate of completing a urinary diary compared to those with a high body mass index.. Obesity correlates with a lower voiding diary completion rate and lower efficacy of treatment in children with nocturnal enuresis or dysfunctional voiding.

Topics: Adolescent; Behavior Therapy; Body Mass Index; Child; Child, Preschool; Cholinergic Antagonists; Comorbidity; Deamino Arginine Vasopressin; Female; Humans; Male; Medical Records; Nocturnal Enuresis; Obesity; Retrospective Studies; Treatment Outcome; Treatment Refusal

Monosymptomatic nocturnal enuresis is frequently associated with nocturnal polyuria and low urinary osmolality during the night. Initial studies found decreased vasopressin levels associated with low urinary osmolality overnight. Together with the documented desmopressin response, this was suggestive of a primary role for vasopressin in the pathogenesis of enuresis in the absence of bladder dysfunction. Recent studies no longer confirm this primary role of vasopressin. Other pathogenetic factors such as disordered renal sodium handling, hypercalciuria, increased prostaglandins and/or osmotic excretion might have a role. So far, little attention has been given to abnormalities in the circadian rhythm of glomerular filtration rate. We evaluated the circadian rhythm of glomerular filtration rate and diuresis in children with desmopressin resistant monosymptomatic nocturnal enuresis and nocturnal polyuria.. We evaluated 15 children (9 boys) 9 to 14 years old with monosymptomatic nocturnal enuresis and nocturnal polyuria resistant to desmopressin treatment. The control group consisted of 25 children (12 boys) 9 to 16 years old with monosymptomatic nocturnal enuresis without nocturnal polyuria.. Compared to the control population, children with nocturnal polyuria lost their circadian rhythm not only for diuresis and sodium excretion but also for glomerular filtration rate.. Patients with monosymptomatic nocturnal enuresis and nocturnal polyuria lack a normal circadian rhythm for diuresis and sodium excretion, and the circadian rhythm of glomerular filtration rate is absent. This absence of circadian rhythm of glomerular filtration rate and/or sodium handling cannot be explained by a primary role of vasopressin, but rather by a disorder in circadian rhythm of renal glomerular and/or tubular functions.

Topics: Adolescent; Case-Control Studies; Child; Circadian Rhythm; Deamino Arginine Vasopressin; Diuresis; Drug Resistance; Female; Glomerular Filtration Rate; Humans; Male; Nocturnal Enuresis; Osmolar Concentration; Polyuria; Prospective Studies; Reference Values; Severity of Illness Index; Sodium; Statistics, Nonparametric; Urodynamics; Vasopressins

Topics: Circadian Rhythm; Deamino Arginine Vasopressin; Neural Inhibition; Nocturnal Enuresis; Reflex, Startle; Sleep; Urinary Bladder; Urination; Urine

Topics: Administration, Intranasal; Adolescent; Child; Deamino Arginine Vasopressin; Female; Hemostatics; Humans; Male; Nocturnal Enuresis; Time Factors

The transition from day to night is associated with a pronounced decline in diuresis with reductions in the amount of excreted water, electrolytes, and other end products of our metabolism. Failure to do so leads to a large urine output at night, a condition known as nocturnal polyuria, encountered in a large proportion of children with nocturnal enuresis. The aim of this study was to clarify the mechanisms responsible for the nocturnal polyuria seen in enuretics with inadequate response to desmopressin (dDAVP). Forty-six enuretics (7-14 yr of age) and fifteen age-matched controls were admitted for a 24-h protocol with standardized fluid and sodium intake, comprising urine collections, blood sampling, and blood pressure monitoring. We included patients with severe enuresis (5 +/- 1 wet nights/wk) showing <50% reduction in wet nights on dDAVP. We characterized the patients on the basis of their nocturnal urine production. The children with nocturnal polyuria excreted larger amounts of sodium and urea at night than nonpolyurics and controls. Solute-free water reabsorption as well as urinary arginine vasopressin and aquaporin-2 excretion were normal in polyurics, and no differences were found in atrial natriuretic peptide, angiotensin II, aldosterone, and renin levels. Urinary prostaglandin E2 (PGE2) excretion was significantly higher in polyurics. The nocturnal polyuria in children with dDAVP-resistant nocturnal enuresis seems to be the result of augmented sodium and urea excretion. The high urinary PGE2 levels found in these children point toward a role for increased prostaglandin synthesis in the pathogenesis of enuresis-related polyuria.

Topics: Adolescent; Aldosterone; Antidiuretic Agents; Aquaporin 2; Arginine Vasopressin; Atrial Natriuretic Factor; Child; Circadian Rhythm; Deamino Arginine Vasopressin; Dinoprostone; Drinking; Drug Resistance; Female; Humans; Male; Natriuresis; Nocturnal Enuresis; Polyuria; Renin; Sodium; Sodium Chloride, Dietary; Urea

Topics: Adult; Anticonvulsants; Antidiuretic Agents; Brain; Brain Edema; Craniocerebral Trauma; Craniotomy; Deamino Arginine Vasopressin; Diazepam; Fatal Outcome; Hematoma, Subdural; Humans; Hyponatremia; Intubation, Intratracheal; Male; Nocturnal Enuresis; Phenytoin; Saline Solution, Hypertonic; Seizures; Sodium; Tomography, X-Ray Computed

Topics: Behavior Therapy; Child; Child, Preschool; Deamino Arginine Vasopressin; Diurnal Enuresis; Female; Humans; Male; Nocturnal Enuresis; Risk Factors

To determine treatment outcomes in Malaysian children with primary nocturnal enuresis using both non-pharmacological methods and oral desmopressin. Data was collected prospectively from children aged 6-18 years who were referred to the Hospital UKM Enuresis Clinic. Treatment was given to those with a baseline wetting frequency of at least six wet nights/14 nights. Three modalities were offered: fluid management, reward system and oral desmopressin. Response was recorded as partial (> or = 50% reduction in WN from baseline) or full (completely dry). Seventy-one healthy children completed 12 weeks of therapy. Twenty-three children (32.4%) responded to non-pharmacological methods alone (4 full and 19 partial). Another 37 children (51.2%) responded to oral desmopressin (32 to 0.2mg, 4 to 0.4mg and 1 to 0.6mg). Thirty-two percent became dry whilst on therapy. The mean wetting frequency during treatment was significantly reduced (p < 0.01) compared to the baseline mean for both the non-pharmacological group and the desmopressin group. Discontinuation of desmopressin after 12 weeks increased the wetting frequency but this was still significantly lower than at baseline (p < 0.01). No adverse ents were recorded. Treatment of primary nocturnal enuresis in Malaysian children is both effective and well tolerated using fluid management strategies, reward systems and oral desmopressin.

Topics: Adolescent; Antidepressive Agents; Antidiuretic Agents; Child; Cholinergic Antagonists; Deamino Arginine Vasopressin; Female; Humans; Malaysia; Male; Nocturnal Enuresis; Outpatient Clinics, Hospital; Prospective Studies; Treatment Outcome; Water-Electrolyte Balance