Combined treatment with enuresis alarm and desmopressin for nocturnal enuresis

Seventy-one children with nocturnal enuresis were enrolled in a controlled trial. The children were allocated to two matched groups. Children in both groups used an enuresis alarm until the end of treatment. Children in the first group were treated with 40/^g of intranasal desmopressin (Desmospray) for up to 6 weeks at the start of treatment with the alarm. During the observation period before treatment there were 2.3 dry nights per week in both groups. At the end of treatment there was a significant difference in the mean number of dry nights per week between the two groups (6.3 in the alarm and desmopressin group and 4.8 in the alarm group) and also in the number of children becoming reliably dry. The combination of desmopressin and alarm was particularly helpful for children with severe wetting and those with family and behavioural problems. Desmopressin, enuresis alarm, nocturnal enuresis
MG Bradbury, Department of Paediatrics and Child Health, St James's University Hospital, Leeds LS9 7TF, UK     

Desmopressin in nocturnal enuresis.

The response of desamino-D-arginine vasopressin (DDAVP) was investigated in 32 enuretic children in a double-blind clinical study. The 15 children treated with DDAVP showed a significant reduction in the incidence of bed wetting--from 18.7 +/- 6.5 to 6.5 +/- 9.2 wet nights per 30 days. In 6 children bed wetting stopped entirely, in 6 there was a satisfactory response, and in 3 the response was marginal or there was none. When DDAVP was stopped most children reverted to their earlier bedwetting habits (15.7 +/- 8.9 nights a month). Response to DDAVP was significantly better in children aged more than 10 years (mean age for the entire group). The administration of DDAVP was not associated with any appreciable change in morning urine osmolalities. No adverse effects were noted. It is concluded that DDAVP is effective in nocturnal enuresis, particularly in older children. It is suggested that the cessation of bed wetting may, in part, reflect functional properties of DDAVP rather than antidiuresis.     

前瞻性随机对照研究生物反馈和口服醋酸去氨加压素治疗儿童原发性遗尿症的疗效

目的: 通过前瞻性随机对照研究比较生物反馈和口服DDAVP两种方法对治疗原发性遗尿症（PNE）的效果。方法：将2005.7-2006.1在复旦大学附属儿科医院确诊为PNE的儿童随机分为DDAVP组和生物反馈组，进行1个月的治疗和其后3个月的随访，指标包括排尿日记，尿流率，尿液AQP2。结果：PNE患儿共50例，男26例，女24例；平均年龄8.4±0.9岁。治疗结束和结束后第3个月时生物反馈组总有效率均高于DDAVP组，两组治愈率和复发率无明显差异。生物反馈组治疗结束时最大尿流率和尿量较治疗前明显提高，正常尿流曲线和逼尿肌-括约肌收缩协调人数较治疗前明显增多。晨尿尿液AQP2主要检测到两个条带，均可见遗尿组灰度显著低于对照组。DDAVP组治疗结束时AQP2与治疗前相比有明显增加。结论：生物反馈和DDAVP均是治疗PNE的有效方法。生物反馈治疗在四个月内的总有效率高于DDAVP，值得在PNE儿童中开展使用。生物反馈治疗对改善膀胱-尿道功能紊乱有帮助，而DDAVP则可以提高尿液中AQP2水平。     

Combined therapy of enuresis alarm and desmopressin in the treatment of nocturnal enuresis

Twenty-eight children with primary nocturnal enuresis were blindly allocated at random to a combination of enuresis alarm and 20 g intranasal desmopressin or alarm and placebo for 2 weeks. Patients received the other therapy after a 2-week treatment-free period. The combined treatment of desmopressin and alarm showed 5.1±0.4 (mean ± SEM) dry nights per week and resulted in significantly more dry nights per week during the 2 weeks of observation than placebo and alarm (4.1±0.4,P<0.05)Abbreviations DDAVP desmopressin - SEM standard error of mean     

Reduced anti-diuretic response to desmopressin during wet nights in patients with monosymptomatic nocturnal enuresis

ObjectiveTo investigate why not all children with monosymptomatic nocturnal enuresis (MNE) treated with desmopressin give an adequate response.Materials and methodsWe 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.ResultsSixty-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.ConclusionThe 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.     

Treatment of isolated nocturnal enuresis: alarm or desmopressin?]

BACKGROUND: Monosymptomatic nocturnal enuresis is common in healthy school children. Treatment is often required because of social and psychological convenience. We therefore conducted a randomized prospective trial using either desmopressin (D) or alarm (A). PATIENTS AND METHODS: Patients (n = 135) aged 6 to 16 years were enrolled between January 1992 and December 1994. Desmopressin (Minirin spray, Ferring SA) was given intranasally at a dose of 20 micrograms at bedtime and increased to 40 micrograms after 2 weeks if partial result was obtained. The alarm was a pad-bell device (Wet-stop, Sega) and the sound source was attached to the upper part of the pajamas. Inclusion criteria were: primary monosymptomatic nocturnal enuresis in healthy children, age > or = 6 years, absence of previous treatment using either desmopressin or alarm. The aim of the treatment was to achieve 100% dry nights. Patients were evaluated after 15 days on therapy by phone call and thereafter by attending the outpatient clinic at 2-3 and 4-6 months. At the time of the second evaluation, a switch from alarm to desmopressin (or vice-versa) was proposed to those who did not respond to the initial treatment. RESULTS: In group D (n = 62), only 27 children were included since 12 (19%) were switched to alarm and 23 (37%) were excluded because they were either non-compliant or lost to follow-up. In group A (n = 73), only 31 were included since six (8%) were switched to desmopressin and 36 (49%) were excluded for the same reasons as in group D. Prior to inclusion, the percentage of dry nights was 21% in group D and 14% in group A. After 15 days on therapy, patients from group D achieved 80% dry nights compared to 50% in group A (P = 0.001). After 3 months, patients from group D attained 85% dry nights vs 90% in group A. After 6 months, children from group A achieved 94% dry nights vs 78% in group D (P = 0.01). CONCLUSION: Desmopressin offers better short-term results than enuresis alarm but the latter is significantly more efficient in the long term. In France, the alarm device is not reimbursed by the national health service and therefore is poorly accepted, as suggested from the high rate of patients lost to follow-up.     

DDAVP and urine osmolality in refractory enuresis.

A double blind crossover trial of 20 micrograms intranasal 1-deamino-8-d-arginine vasopressin (DDAVP) versus placebo was carried out in 17 children with intractable enuresis aged between 6 and 13 years who had failed to respond to drugs and an enuresis alarm. Fluid intake was not restricted. There was a significant reduction in the number of wet nights. Seven children (41%) were cured or showed considerable improvement, with strong evidence against any placebo effect. The best response was seen in children aged 10 years or over and if urine osmolality after DDAVP reached beyond 1000 mmol/kg or was already at this concentration. The degree of overnight rise in urine osmolality after treatment with DDAVP was not predictable but correlated well with the clinical improvement in nocturnal diuresis present in eight of the children. A further 12 children with equally refractory enuresis were given 20 micrograms of the active drug to take during their school journeys or holidays. Six of them had previously normal overnight urine osmolalities with only two successes, but of the six who had nocturnal diuresis before treatment, five became dry, suggesting that DDAVP acts largely by anti-diuresis and might be most useful in children with nocturnal polyuria.     

Desmopressin response of enuretic children. Effects of age and frequency of enuresis

To characterize the children with enuresis likely to respond to desmopressin acetate, we performed a double-blind crossover study that included the use of a placebo. During the two weeks of desmopressin administration, six children (12%) had 13 or 14 dry nights, and 15 children (29%) had eight to 12 dry nights. Among the 17 children aged 9 years or older, with four to seven dry nights during the two-week baseline period, 12 children (71%) responded to desmopressin (eight to 14 dry nights). In contrast, none of the 15 children younger than 9 years of age with fewer than three dry nights before therapy responded. During the posttreatment period, only four of the 21 drug responders reported a persistent effect. Desmopressin may be effective in reducing the frequency of enuresis, especially in children older than 9 years of age without nightly enuresis.     

Efficacy and safety during long-term treatment of primary monosymptomatic nocturnal enuresis with desmopressin. Swedish Enuresis Trial Group

The Swedish Enuresis Trial (SWEET) was conducted to evaluate the long-term safety and efficacy of intranasal desmopressin treatment in children with primary, monosymptomatic nocturnal enuresis (PMNE). The study had an open, multicentre design and comprised a 4-wk observation period, a 6-wk dose titration period (with 20-40 microg desmopressin) and a 1-y, long-term treatment period. A treatment-free week was introduced every 3 mo to identify dry patients. In total, 399 children aged 6-12 y with PMNE were recruited. Of these, 245 patients (61%) experienced > or = 50% reduction in the number of wet nights during the last 4 wk of dose titration compared with the observation period. These responders entered the long-term phase of the trial. The mean number of wet nights per week decreased from a median of 5.3 (range 1.3-7.0) during the observation period to a median of 0.8 (range 0.0-5.0) during the last 3-mo period. Seventy-seven children became dry, 63 (83%) within 6 mo of treatment initiation. The percentage of children who became dry was similar in all age groups. Significantly fewer children in the lowest age group were defined as responders (52%; 95% CI 45, 59) among the 6-7-y-olds compared to 65% (56, 74) and 81% (72, 90) in the two older age groups. Desmopressin was well tolerated. No serious drug-related adverse events were recorded and no clinical symptoms of hyponatraemia were reported. The SWEET trial has demonstrated that desmopressin is both safe and effective for the long-term treatment of PMNE, with a significant therapeutic effect also in children of 6-7 y of age.     

Oxybutinin-desmopressin association in the treatment of primary nocturnal enuresis with diurnal urination disorders]

BACKGROUND: Since most of the children observed in our Centre present enuresis with voiding disturbance, we carried out a study where these patients were treated with the DDAVP + Oxybutinin association. METHODS: We have treated 89 children with enuresis and voiding disturbances (urge incontinence, voiding urgency, urinated > 7 times a day), administering a drugs combination of desmopressin (20 micrograms/daily) and oxybutinin (0.3-0.6 mg/kg/bid or tid) for a variable period, depending on response to the treatment. RESULTS: The results demonstrate the efficacy of this association: we have observed a reduction in average bed wetting nights from 23.4 nights/month to 6.4 wet nights after 1 month, to 3.8 ad 2.9 respectively after 3 and 6 months from the beginning. Moreover we obtained a recovery of all daily voiding disturbances after 3 months. Fifty percent of children were cured after 4 months of therapy and finally 93.2% recovered at 6 months. On the other hand, 2 children were no-responders to the therapy even after 9 months of combined drugs administration. CONCLUSIONS: Based on these results we can affirm that children with nocturnal enuresis and voiding disturbance can be treated with this combined therapy. Actually, the reduction of urinary output and thus lower bladder filling, due to the desmopressin, decreases the onset of uninhibited bladder contractions and enhances oxybutinin activity.     

Desmopressin for bed wetting: length of treatment, vasopressin secretion, and response.

Fifty five children with nocturnal enuresis referred to a hospital enuresis clinic entered a controlled trial to compare the efficacy of one month and three month courses of intranasal desmopressin (Desmospray). There was no significant difference in outcome between the two groups. Overall 36% improved by at least two dry nights/week during treatment, but only five children (18%) in the one month group and three (11%) in the three month group became completely dry and only one in each group remained dry after treatment. To determine whether nocturnal polyuria was associated with a therapeutic response to desmopressin, the nocturnal urine volume, osmolality, and vasopressin concentration were measured in desmopressin responsive enuretics, desmopressin non-responders, and non-enuretic control children. There were no significant differences between the three groups. A three month course of desmopressin is no more effective than a one month course. Although many children will improve during treatment, only a small number become dry and most will relapse when treatment is stopped.     

Evidence against a synergistic effect of desmopressin with conditioning in the treatment of nocturnal enuresis

OBJECTIVE: To test the hypothesis that desmopressin facilitates acquisition of continence, we aimed to establish whether, in children with nocturnal enuresis who are desmopressin nonresponders, adjunct desmopressin increases the rate of sustained continence after treatment with a conditioning alarm.Study design Patients with nocturnal enuresis (n=358; age range, 6-16 years) completed a 4-week "run-in" course of intranasal desmopressin (20-40 microg). Of these, 207 defined as nonresponders (<50% reduction in wet nights) were randomly assigned to receive either desmopressin (n=101) or placebo (n=106) nasal spray, together with conditioning alarm therapy for 8 weeks. Principal outcome measures were remission (28 continuous dry nights) and relapse (>2 wet nights in 2 weeks after having achieved remission). RESULTS: Remission rates were similar in both groups (51.5% desmopressin, 48.1% placebo; 95% CI on difference, -10%, 17%; P=.63), and relapse rates were not significantly different (13.5% vs 5.9%; 95% CI on difference, -3.7%, 19%; P=.19). Although remission rates were similar, children treated with desmopressin had significantly more dry nights during treatment than those in the placebo group. CONCLUSIONS: Desmopressin did not act synergistically with alarm treatment to achieve remission. Therefore, we infer that in partial or nonresponders, desmopressin does not enhance learning.     

Methotrexate versus cyclosporine in the treatment of severe atopic dermatitis in children: a multicenter experience from Egypt

Topical therapy is usually of limited benefit in the treatment of severe atopic dermatitis (AD), and the need for a safe and effective systemic treatment may be required in certain cases especially in children. We evaluated the efficacy and safety of methotrexate and cyclosporine in the treatment of 40 children with severe AD. Patients were divided into two groups (each consisting of 20 patients); group A was treated with methotrexate (7.5 mg/week) while group B was treated with cyclosporine (2.5 mg/kg/day). The severity scoring for atopic dermatitis (SCORAD) was used to indicate efficacy of treatment. In group A, the mean SCORAD score at the beginning of the study was 57.90?±?3.21 that was reduced at the end of the treatment period to reach 29.35?±?6.32 with a mean absolute reduction of 26.25?±?7.03. In group B, the mean SCORAD score was 56.54?±?4.82 at the start of treatment and was 31.35?±?8.89 at the end of 12 weeks of treatment. The mean absolute reduction was 25.02?±?8.21. There was no statistically significant difference in the reduction of SCORAD score between both groups (P?±?0.93). Mild and temporary adverse effects were reported in some patients in both groups. Conclusion: Methotrexate or cyclosporine in low doses can be considered as effective, relatively safe, and well-tolerated treatments for severe AD in children.     

醋酸去氨加压素联合膀胱训练治疗儿童原发性遗尿症的疗效

目的观察醋酸去氨加压素(DDAVP)联合膀胱训练治疗儿童原发性遗尿症(PNE)的疗效及复发率。方法采用前瞻性实验研究方法,将2007年1月-2008年12月在本院儿科遗尿专科门诊就诊的100例PNE患儿随机分为对照组和观察组,每组各50例。对照组单纯应用DDAVP口服治疗;观察组在应用DDAVP口服治疗的同时进行膀胱训练,疗程均为3个月。疗程结束比较2组疗效。疗程结束随访3个月,比较2组远期、近期复发率。应用SPSS 13.0软件进行统计学分析。结果对照组总有效率为72.9%,近期复发率为22.9%,远期复发率为54.3%;观察组总有效率为91.3%,近期复发率为11.9%,远期复发率为28.6%。观察组总有效率显著高于对照组(Z=-1.972,P=0.049),2组近期复发率比较差异无统计学意义(χ2=1.632,P=0.201),观察组远期复发率显著低于对照组(χ2=5.249,P=0.022)。结论DDAVP联合膀胱训练治疗PNE疗效显著,且能降低远期复发率。     

Prospective, randomized, investigator-blinded study of the efficacy and safety of meropenem vs. cefotaxime therapy in bacterial meningitis in children. Meropenem Meningitis Study Group.

OBJECTIVES: To compare the efficacy and safety of meropenem with cefotaxime for the treatment of infants and children with bacterial meningitis. METHODS: Infants and children with strongly suspected or documented bacterial meningitis were randomly assigned in a prospective multicenter study to receive either meropenem or cefotaxime. Patients were assessed at the end of therapy and at 5 to 7 weeks and 5 to 7 months after the end of treatment for the presence of neurologic and sensory neural sequelae. RESULTS: A total of 258 children were randomized to either treatment group. A further 8 patients with suspected pneumococcal meningitis were treated with meropenem without randomization. Of the randomized patients 154 were fully evaluable, 79 in the meropenem group and 75 in the cefotaxime group. At the end of treatment there were no significant differences in clinical outcome between the two treatment groups. Clinical cure with or without sequelae was achieved in 97 and 96% of the meropenem- and cefotaxime-treated patients, respectively. At the end of treatment and at 5 to 7 weeks, 46 and 54% of meropenem patients were cured with no sequelae, respectively. Corresponding results for cefotaxime patients were 56 and 58%. All pathogens were eradicated. In total 37 patients had seizures during treatment, 15 (12%) in the meropenem and 22 (17%) in the cefotaxime group. None of the seizures was considered to be drug-related. CONCLUSIONS: This trial shows that meropenem is suitable therapy for bacterial meningitis in infants and children and that it offers an efficacy and safety profile similar to that of cefotaxime.     

Lack of benefit of laxatives as adjunctive therapy for functional nonretentive fecal soiling in children

OBJECTIVES: To determine whether the combination of laxative treatment and biofeedback therapy (BF) is more effective for management of functional nonretentive fecal soiling than biofeedback therapy alone. STUDY DESIGN: In a prospective nonblinded study, 48 children were randomized in 2 groups: treatment with oral laxatives (LAX) and 5 sessions of BF (BF + LAX) or 5 sessions of BF alone (BF) during a treatment intervention period of 7 weeks. Biofeedback was performed with perfused manometry catheters and rectal balloon distension. Training focused on awareness of balloon distension and instruction in correct defecation dynamics. Successful treatment was defined as <1 encopresis episode per 2 weeks. RESULTS: At the end of the intervention period, the number of encopresis episodes was significantly decreased in both groups: from 7 (2 to 24) to 2 (0 to 17) in the BF group and from 7 (3 to 25) to 2 (0 to 14) in the BF + LAX group. However, children given BF alone had significantly higher success rates than children treated with BF and additional oral laxatives (44% to 11%). CONCLUSIONS: There is no additional effect of laxative treatment in functional nonretentive fecal soiling. Children treated with BF in combination with laxatives showed a significantly lower success percentage compared with those treated with BF alone. These results suggest that children with functional nonretentive fecal soiling should be treated differently from children with constipation and encopresis.     

Nocturnal enuresis: a placebo controlled trial of two antidepressant drugs.

A multicentre, randomised, double blind treatment trial was set up comparing imipramine (a tricyclic antidepressant with anticholinergic action), mianserin (a quadricyclic antidepressant without anticholinergic activity), and placebo, (a) possibly to identify an effective alternative drug and (b) to elucidate the action of imipramine in enuretic children. Eighty children (65 boys, 15 girls) aged 5-13 years, wet three or more nights a week, were studied. Exclusions were a urinary tract infection or abnormality, other organic illness, or severe emotional disorders. After a four week assessment, 25 children were randomised to eight weeks'' treatment with imipramine 25 mg, 26 to mianserin 10 mg and 29 to placebo, followed by four weeks without treatment. Dry nights and a wetness score were recorded throughout. During treatment, imipramine was superior to both placebo and mianserin (p < 0.001) in achieving dry nights and reducing wetness scores. It led to a definite improvement in 72% of children. Mianserin produced a mildly beneficial effect that was not superior to placebo. No side effects were recorded. Mianserin would not be a satisfactory alternative treatment for nocturnal enuresis. The efficacy of imipramine is unlikely to be the result of its antidepressant activity.     

托特罗定叠加槐杞黄颗粒和心理行为干预治疗晨尿渗透浓度正常的原发性遗尿症患儿的随机平行对照研究

目的 对去氨加压素(DDAVP)治疗无效的、晨尿渗透浓度正常的原发性遗尿（PNE）患儿,以托特罗定为基础叠加槐杞黄颗粒和心理行为干预,寻求最佳治疗方案。方法 对DDAVP治疗无效的PNE门诊患儿经过 1个月的药物洗脱期,以区组随机方法分为3组：西药组（托特罗定）、中西药组（托特罗定+槐杞黄颗粒）和联合组（托特罗定+槐杞黄颗粒+心理行为干预）行平行随机对照试验,入组时依据患儿及其家长回忆的月遗尿次数视为基线遗尿次数,在治疗结束时（近期）和治疗结束后3个月（远期）评估疗效并行意向性分析。结果 符合纳入排除标准的234例PNE患儿进入本文分析,3组各78例,3组间年龄、性别和基线遗尿次数差异均无统计学意义（P均>0.05）;近期和远期总有效率,联合组和中西药组均好于西药组,差异有统计学意义（P分别为0.017和<0.001）;近期总有效率,联合组与中西药组差异无统计学意义（P>0.05）,远期总有效率,联合组与中西药组差异有统计学意义（P＝0.005）,联合组近期和远期得到1例有益结果需要治疗PNE人数（NNT）分别为6.5（95％CI：3.7～25.3）和2.4（95％CI：1.8～3.6）,中西药组远期NNT为和4.6(95％CI:2.7～15.2)。结论 托特罗定+槐杞黄颗粒+心理行为干预2.4例DDAVP治疗无效的晨尿渗透浓度正常的PNE患儿在远期疗效上有1例有效,而且置信区间很窄,对这一结果信心很大。     

Comparison of desmopressin and enuresis alarm for nocturnal enuresis.

Fifty children with primary nocturnal enuresis were randomised for a study comparing desmopressin (DDAVP) and enuresis alarm. Forty six completed the trial, 24 of whom were treated with 20 micrograms intranasal desmopressin nightly and 22 with enuresis alarm for three months. Failures were crossed over and relapses were continued on the same treatment for a further three months. The improvement rate was 70% in the group given desmopressin and 86% in the group treated with alarm; the difference was not significant. During the first week of treatment the group given desmopressin was significantly dryer, and at the end of the study 10 of these patients relapsed compared with one patient in the group given the alarm. No serious side effects were observed. This study confirms the role of conditioning treatment as preferable in long term treatment of nocturnal enuresis. When this fails or when a safe drug with rapid effect is needed, however, desmopressin is a useful alternative.     

遗尿报警器治疗学龄前儿童原发性单症状性夜遗尿症的临床研究（附95例报告）

目的　探讨遗尿报警器治疗学龄前儿童原发性单症状性夜遗尿症的疗效。方法　选取2017年1月至2018年7月在首都儿科研究所附属儿童医院收治的中重度原发性单症状性夜遗尿症患儿95例,年龄3.5～6.0岁。按照随机分组的方法,其中治疗组53例采用遗尿报警器治疗,对照组42例采用基础治疗。治疗3个月或达到连续干床14d（治疗成功）停止。治疗成功者停止治疗1个月,记录复发例数。重新报警器治疗3个月,观察疗效。结果　治疗组7例（13.2%）未达疗程退出,余46例中治疗完全有效（FR）29例,部分有效（PR）7例,治疗无效（NR）10例。其中FR组25例治疗成功,治疗成功所需疗程最短42d。治疗成功者停止治疗1个月,复发例数11例。8例重新使用报警器治疗3个月,均可达到治疗完全有效。对照组3例（7.1%）失访,39例观察3个月,均未达到连续干床14 d。对照组FR 0例,PR 17例,NR 22例。两组治疗完全有效率采用Fisher精确概率法检验,差异有统计学意义（χ2＝55.10,P＝0.00）。报警器治疗NR组,5例（50%）患儿年龄＜4岁,而FR+PR组,仅有3例（8.3%）年龄＜4岁,采用P earson卡方检验,差异有统计学意义（χ2＝9.457,P＝0.007）。入组患儿均未发现严重不良反应。结论　遗尿报警器治疗学龄前儿童原发性单症状性夜遗尿症患儿安全、 有效,报警器干预的年龄以4岁以上为宜。报警器是逐渐起效的,获得成功治疗的时间＞1个月。