VOLUME 8 NUMBER 2 2003 ISSN: 0965-0288

Effective Bulletin on the effectiveness of health service interventions for decision makers

This bulletin summarises the research evidence on the effects of interventions for the treatment of nocturnal enuresis in children

Health Care Treating nocturnal enuresis in children ■ Nocturnal enuresis in children (bedwetting) affects many families. Although it has a high rate of spontaneous remission, bedwetting may bring social and emotional stigma, stress and inconvenience to both the child and their family. ■ A variety of interventions are used to treat nocturnal enuresis. These include alarms, drugs such as desmopressin, simple behavioural methods such as star charts, as well as more complex multi-faceted interventions. ■ Much of the available research evaluating the effects of interventions is of poor quality and there are few direct comparisons between different types of intervention. ■ Simple behavioural interventions are widely used as standard first-line treatment, but they require a high level of parental

involvement. Currently, there is insufficient evidence to support the use of any particular intervention. ■ The use of alarms has been shown to reduce night-time bedwetting both during treatment and after treatment stops. Before embarking on alarm treatment, families need to be made aware of both the time and the high level of parental involvement necessary to attain success. ■ Drug therapy such as desmopressin reduces the number of wet nights per week compared with placebo, but only for as long as the drug is used. Drugs could be used to reduce bedwetting for a specific purpose, such as nights away from home. Children and their families need to be warned about possible side effects of some of the drugs.

CENTRE FOR REVIEWS AND DISSEMINATION

A. Background Nocturnal enuresis (bedwetting) is the involuntary loss of urine at night, in the absence of physical disease, at an age when a child could reasonably be expected to be dry (by consensus, at a developmental age of five years).1,2 Although bedwetting has a high rate of spontaneous remission, it may bring social and emotional stigma, stress and inconvenience to both the child with enuresis and their family.3 Children who wet the bed may experience parental disapproval, sibling teasing and repeated treatment failure which may lower self esteem.4,5

Prevalence and causes Nocturnal enuresis affects many families. Estimating the prevalence is difficult, however, because there are variations in methods of diagnosis and in definitions.6,7 In the UK, the most recent estimates suggest that the prevalence of frequent bedwetting (more than once a week) is higher in boys and shows a steady decline with age.8-10 Around one in six of five-year-olds regularly wet the bed compared to around one in twenty 11-year-olds.8-10 The causes of primary nocturnal enuresis, where a child has never been dry at night, are unclear. Genetic,2,11-13 physiological14,15 and psychological16-19 factors, as well as delay in maturation of the mechanism for bladder control,20,21 have been suggested. Other factors which may contribute to bedwetting include: constipation, sleep apnoea and upper airway obstructive symptoms22 and diet or mild caffeine drinks with diuretic effects (e.g. cola).8

B. Management of enuresis A wide variety of interventions are used to treat nocturnal enuresis. These include enuresis alarms, drugs

2

Box 1 Interventions used to treat nocturnal enuresis

Behavioural interventions ■ Lifting: involves taking the child to the toilet during the night usually before the time that bedwetting is expected, without necessarily waking the child. ■ Waking: involves waking the child to allow them to get up and urinate. ■ Reward systems (e.g. star charts): the child might receive a star for every dry night, and a reward after a preset number of stars have been earned. ■ Retention control training: attempting to increase the functional bladder capacity by delaying urination for extended periods of time during the day. ■ Stop-start training: teaching children to interrupt their stream of urine in order to strengthen their pelvic floor muscles ■ Dry bed training: can include enuresis alarms, waking routines, positive practice, cleanliness training, bladder training, and rewards. Enuresis alarms ■ Enuresis alarms: wake the child in the night at the onset of wetting. When a child begins to urinate, a sensor (either a bed pad or one worn inside pyjamas) is moistened, and the alarm is triggered. ■ Over-learning: may be initiated after successful alarm treatment (e.g. achievement of 14 consecutive dry nights). Extra drinks are given at bed-time to cause additional stress to the detrusor muscles in the bladder. Alarm treatment is then continued until 14 consecutive dry nights are once again achieved. Pharmacological interventions ■ Drugs: include desmopressin and, less commonly, tricyclic drugs such as imipramine, amitriptyline and nortriptyline. such as desmopressin, simple behavioural methods such as star charts and more complex behavioural methods including dry bed training. Other less common interventions include psychotherapy, surgery, fluid deprivation and complementary therapies. Box 1 describes the most commonly used behavioural, alarm and pharmacological interventions. Treatment for children who wet the bed is often carried out by health professionals in general practice. Bedwetting may be discovered when a child is seen for a complaint other than enuresis. Having established that the child is at an age where one could reasonably expect a dry bed (i.e. at least five years old) and wants

EFFECTIVE HEALTH CARE Treating nocturnal ensuresis in children

to become dry,23 consensus is that a thorough assessment should be undertaken including a general physical examination, urinalysis and investigation of attitudes.8 In keeping with the objectives of the National Service Framework for Children, any intervention should be centred on the needs of the child.27 Although it is yet to be subjected to rigorous evaluation, the ‘three systems approach’24 is advocated as a way to understand, assess and select appropriate treatment for nocturnal enuresis. The Enuresis Resource and Information Centre (ERIC) has produced guidelines on minimum standards of practice in the treatment of enuresis to assist

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managers and practitioners in the planning, execution and evaluation of enuresis services.25 ERIC also has details of over 600 enuresis clinics in the UK.26 Some clinics are based in hospitals and others in health centres (often run by school nurses) Most but not all clinics are open to clients without the need for a professional referral.

C. Nature of the evidence This issue of Effective Health Care summarises the research evidence from randomised controlled trials (RCTs) on the effects of interventions for the treatment of nocturnal enuresis in children. The bulletin is based upon a series of systematic reviews that have been carried out by the Cochrane Incontinence Group, and are available via the Cochrane Library. The Cochrane reviews are all based on a previous systematic review originally published in 1997 as part of the CRD

Outcome:

Report series.28 Further details of review methods are available in the Appendix. Although over 100 RCTs have been identified across the Cochrane reviews, there are few direct comparisons between different types of intervention. The difficulty in comparing interventions is exacerbated by the lack of uniformity in outcome measures and the failure of some studies to adequately assess baseline levels of bedwetting. Many of the included RCTs have methodological problems such as small sample sizes and high rates of attrition (drop-outs), leading to low statistical power and potential bias. In addition, many are poorly reported. For example, many trial authors give insufficient detail about the method of randomisation or inadequately report follow-up data.

In addition, strict inclusion/exclusion criteria were imposed in many of the trials. Consequently, the children involved are not necessarily representative of the wider population of those who wet the bed, either in the community or in institutions.

D. Effects of interventions D1. Behavioural interventions other than alarms Simple behavioural interventions are widely used as standard first-line treatment. Twelve RCTs were included in a Cochrane review assessing the effects of simple behavioural interventions.29 None of the RCTs were of good methodological quality. The review found that star charts, whether with or without lifting or waking, were associated with fewer wet nights and lower failure rates while on treatment, and longer-term success after treatment. However, each finding was based on a single

A number of the included RCTs have recruited children by advertising in the media, or from enuresis clinics. Participating families may have been especially motivated to tackle the bedwetting.

Number cured (achieving 14 consecutive dry nights)

Study or sub-category

alarm n/N

01 alarm vs control Werry 1965 6/21 Sloop 1973 11/21 Sacks 1974 51/64 Jehu 1977 18/19 Bollard 1981a 12/15 Bollard 1981b 16/20 Wagner 1982 10/12 Lynch 1984 7/18 Bennett 1985 4/9 Wagner 1985 8/13 Houts 1986 9/12 Moffatt 1987 42/61 Ronen 1992 12/19 Subtotal (95% CI) 304 Total events: 206 (alarm), 9 (control) 2 Test for heterogeneity: Chi = 7.40, df = 12 (P = 0.83), I2 = 0% Test for overall effect: Z = 9.20 (P < 0.00001) 02 delayed alarm vs control 1/18 Lynch 1984 7/13 Wagner 1985 31 Subtotal (95% CI) Total events: 8 (alarm), 1 (control) Test for heterogeneity: Chi2 = 0.20, df = 1 (P = 0.65), I2 = 0% Test for overall effect: Z = 2.08 (P = 0.04) 03 unsupervised alarm vs control Bollard 1981a

9/15

control n/N

RR (fixed) 95% CI

Weight %

RR (fixed) 95% CI

1/27 1/21 2/9 0/20 0/15 2/20 1/12 0/18 0/9 1/13 0/11 1/55 0/18 248

6.50 7.43 26.07 3.63 3.72 14.87 7.43 3.72 3.72 7.43 3.86 7.82 3.81 100.00

7.71 [1.00, 59.25] 11.00 [1.56, 77.76] 3.59 [1.05, 12.25] 38.85 [2.50, 602.54] 25.00 [1.61, 387.35] 8.00 [2.11, 30.34] 10.00 [1.51, 66.43] 15.00 [0.92, 244.51] 9.00 [0.55, 146.11] 8.00 [1.16, 55.20] 17.54 [1.14, 269.84] 37.87 [5.39, 266.00] 23.75 [1.51, 373.78] 12.55 [7.32, 21.53]

0/18 1/13 31

33.33 66.67 100.00

3.00 [0.13, 69.09] 7.00 [1.00, 49.16] 5.67 [1.11, 28.99]

0/15

100.00

19.00 [1.20, 299.63]

0.001 0.01

0.1

favours control

1

10

100

1000

favours alarm

Figure 1 Comparison: alarm vs control – number cured during treatment

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EFFECTIVE HEALTH CARE Treating nocturnal ensuresis in children

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Outcome:

Numbers remaining cured (achieving 14 dry nights and not relapsing)

Study or sub-category

Treatment n/N

01 alarm vs control Sloop 1973 7/21 Bollard 1981a 8/15 Bollard 1981b 10/20 Wagner 1982 5/12 Wagner 1985 6/13 Subtotal (95% CI) 81 Total events: 36 (Treatment), 1 (Control) Test for heterogeneity: Chi2 = 0.52, df = 4 (P = 0.97), I2 = 0% Test for overall effect: Z = 4.37 (P < 0.0001)

Control n/N

RR (fixed) 95% CI

RR (fixed) 95% CI

1/21 0/15 0/20 0/12 0/13 81

33.33 16.67 16.67 16.67 16.67 100.00

7.00 [0.94, 52.04] 17.00 [1.07, 270.41] 21.00 [1.31, 335.74] 11.00 [0.67, 179.29] 13.00 [0.81, 209.42] 12.67 [4.06, 39.52]

02 delayed alarm vs control Wagner 1985

2/13

0/13

100.00

5.00 [0.26, 95.02]

03 unsupervised alarm vs control Bollard 1981a

4/15

0/15

100.00

9.00 [0.53, 153.79]

0.001 0.01

0.1

1

favours control

Figure 2

10

100

1000

favours alarm

Comparison: alarm vs control – numbers remaining cured after treatment

small trial. Of the two trials addressing retention control training, one was too small to provide meaningful information, and the other had a very high (80%) dropout rate. Another small trial showed that there might be some benefits associated with cognitive therapy compared with star charts, but these findings will need to be confirmed in larger trials. A feature of the included RCTs was high dropout or non-adherence rates. Families reported that waking the child at night was disruptive and stressful, suggesting that some of these simple behavioural interventions are not suitable for all. A number of RCTs have assessed the effects of complex behavioural treatment programmes such as dry bed training. In the 1997 systematic review undertaken by CRD,28 complex behavioural treatment programmes such as dry bed training were not found to be more effective than alarm treatment. An update is nearing completion and will be available as a Cochrane review later this year.30

D2. Alarms Fifty-three RCTs were included in a Cochrane review assessing the effects of alarm interventions for nocturnal enuresis.31 The methodological quality of many of the RCTs was poor. Many were too small to be

4

Weight %

likely to find statistically significant differences, even where some difference may exist, and often only one small trial compared alarms with another method. In these circumstances, no conclusions can be drawn. Do alarms work? The review’s main findings were that alarm treatment was more effective during treatment than control interventions (see Figure 1). In terms of success rates once treatment was completed (see Figure 2), about half the children remained dry after using alarms, compared with almost none of those who received no treatment or waiting list control. Which type of alarm is best? Most of the alarms evaluated were of the type that woke the child immediately by means of a bell or buzzer. Insufficient evidence was found to draw conclusions about the relative effectiveness of different types of alarm. There was some limited evidence that an immediate alarm was better than a delayed alarm, and that one which woke the child rather than the parents had better results. Children were reported to prefer a body-worn alarm to a bed pad and alarm. Are alarms better than other behavioural interventions? The Cochrane review included eight RCTs comparing alarms with a

EFFECTIVE HEALTH CARE Treating nocturnal ensuresis in children

variety of simple behavioural interventions including star charts, rewards, wakening, lifting and stopstart training (pelvic floor muscle training).31 Most of the trials comparing behavioural interventions with alarms tended to favour alarms. In one small trial, alarms were found to be better than stop-start training in terms of wet nights per week both during and after treatment. There were no statistically significant differences between alarms and methods such as lifting, wakening or rewards in four other small trials, although all trials favoured alarms in respect of a reduction in the mean number of wet nights. There was not enough evidence to conclude whether supplementing alarm treatment with behavioural interventions improved the effectiveness of the alarm. Are alarms better than drugs? The Cochrane review included 18 RCTs that involved comparisons between alarms and drugs either alone or in combination.31 Limited evidence suggested that alarms were better than drug treatment. Although desmopressin appeared to have a more immediate effect, alarms were more effective by the end of a course of treatment (RR 0.71, 95% CI 0.50 to 0.99) and after treatment stopped (RR 0.27, 95% CI 0.11 to 0.69). Alarms were also found to be better than tricyclics both during

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Outcome:

Number of wet nights per week during treatment

Study or sub-category

N

Desmopressin Mean (SD)

N

01 10 mcg vs placebo Aladjem 1982 15 1.52(2.15) Kjoller 1984 13 2.49(2.52) Subtotal (95% CI) 28 2 Test for heterogeneity: Chi = 1.68, df = 1 (P = 0.20), I2 = 40.4% Test for overall effect: Z = 4.01 (P < 0.0001) 02 20 mcg vs placebo Folwell 1997 Tuvemo 1978 Segni 1982 Post 1983 B Kjoller 1984 Terho 1984 Janknegt 1990 Rushton 1995 Skoog 1997 Sener 1998 Schulman 2001a Schulman 2001b

31 18 20 20 12 54 22 49 33 31 44 109

3.24(2.51) 1.60(1.82) 2.20(1.34) 4.90(1.92) 2.45(1.84) 2.16(2.00) 3.40(2.50) 3.96(2.37) 4.00(1.15) 1.10(1.39) 4.00(1.33) 4.00(1.57)

03 40 mcg vs placebo Post 1983 A 52 3.90(2.34) Janknegt 1990 22 3.80(2.20) Martin 1993 22 2.16(2.25) Skoog 1997 33 3.50(1.44) Yap 1998 34 2.50(2.70) Schulman 2001a 48 3.50(1.73) Subtotal (95% CI) 211 Test for heterogeneity: Chi2 = 3.11, df = 5 (P = 0.68), I2 = 0% Test for overall effect: Z = 7.63 (P < 0.00001) 04 60 mcg vs placebo Skoog 1997 33 3.50(1.15) Schulman 2001a 48 3.00(1.73) Subtotal (95% CI) 81 2 Test for heterogeneity: Chi = 0.00, df = 1 (P = 1.00), I2 = 0% Test for overall effect: Z = 7.08 (P < 0.00001) 05 combined dose vs placebo Birkasova 1978

22

2.10(2.25)

06 dose titration vs placebo Rushton 1995 49 3.77(2.52) Schulman 2001b 99 3.20(1.69) Subtotal (95% CI) 148 2 Test for heterogeneity: Chi = 1.52, df = 1 (P = 0.22), I2 = 34.3% Test for overall effect: Z = 6.25 (P < 0.00001)

Placebo Mean (SD)

WMD (fixed) 95% CI

4.40(1.94) 3.84(2.13)

62.07 37.93 100.00

-2.88 [-4.31, -1.45] -1.35 [-3.17, 0.47] -2.30 [-3.42, -1.18]

31 18 20 20 12 54 22 47 36 25 47 38

4.86(1.95) 3.97(2.20) 4.20(1.79) 5.80(1.14) 3.84(2.13) 4.02(1.83) 5.30(1.80) 4.90(1.64) 5.00(1.20) 5.10(2.00) 4.50(1.37) 5.00(1.54)

4.29 3.09 5.59 5.61 2.12 10.27 3.24 8.14 17.46 6.29 17.45 16.45

-1.62 [-2.74, -0.50] -2.37 [-3.69, -1.05] -2.00 [-2.98, -1.02] -0.90 [-1.88, 0.08] -1.39 [-2.98, 0.20] -1.86 [-2.58, -1.14] -1.90 [-3.19, -0.61] -0.94 [-1.75, -0.13] -1.00 [-1.55, -0.45] -4.00 [-4.92, -3.08] -0.50 [-1.05, 0.05] -1.00 [-1.57, -0.43]

52 22 22 36 34 47 213

5.00(1.91) 5.30(1.80) 3.68(2.25) 5.00(1.20) 4.50(2.10) 4.50(1.37)

17.27 8.25 6.58 29.47 8.81 29.62 100.00

-1.10 -1.50 -1.52 -1.50 -2.00 -1.00 -1.33

36 47 83

5.00(1.20) 4.50(1.37)

56.09 43.91 100.00

-1.50 [-2.05, -0.95] -1.50 [-2.13, -0.87] -1.50 [-1.92, -1.08]

22

5.50(2.20)

100.00

-3.40 [-4.71, -2.09]

47 36 83

4.90(1.82) 5.00(1.54)

32.13 67.87 100.00

-1.13 [-2.01, -0.25] -1.80 [-2.40, -1.20] -1.58 [-2.08, -1.09]

-10

-5

0

5

[-1.92, [-2.69, [-2.85, [-2.13, [-3.15, [-1.63, [-1.67,

-0.28] -0.31] -0.19] -0.87] -0.85] -0.37] -0.99]

10

favours placebo

Comparison: Desmopressin vs placebo

(RR 0.73, 95% CI 0.61 to 0.88), and after treatment stopped (RR 0.58, 95% CI 0.36 to 0.94). Insufficient reliable evidence was found to support the practice of supplementing alarm treatment with drug interventions. Acceptability of alarms Most alarms wake the child immediately using a bell or buzzer but then require nightwear, and perhaps bedding, to be changed. High dropout rates in some of the trials included in the Cochrane review suggest that there were problems with adherence, often reflecting the unacceptability of the intervention. Potential difficulties, such as the time needed to attain success and the disruption to the family, need to be discussed before embarking on alarm treatment. In two trials, non-

2003

WMD (fixed) 95% CI

17 12 29

favours desmopressin

Figure 3

Weight %

VOLUME 8 NUMBER 2

adherence or dropout was attributed to the equipment being too difficult or complicated to use. A small number of RCTs included in the review involved alarms that delivered electric shocks to the children’s skin. The use of these alarms was clearly unacceptable to parents and children, and they sometimes caused side effects such as skin burns and ulceration.

D3. Drugs Three Cochrane reviews have assessed the effects of drug therapy on nocturnal enuresis in children.32-34 One of these reviews covers the less commonly used drugs and is currently being updated and will be available later this year.34 Forty-one RCTs were included in a Cochrane review assessing the effects of desmopressin.32 The review found that there was clear evidence

that desmopressin (in a variety of doses and forms) was better at reducing the number of wet nights per week during treatment compared to placebo (see Figure 3). However, after treatment stopped, the limited evidence available suggested that this improvement was not sustained. Another Cochrane review of 54 RCTs found that treatment with tricyclic or related drugs (imipramine, amitriptyline, viloxazine, clomipramine and desipramine but not mianserin) was associated with a reduction of about one wet night per week while on treatment.33 For example, imipramine was better at reducing the number of wet nights per week during treatment compared to placebo (WMD -1.19, 95% CI -1.56 to -0.82).

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However, although about a fifth of the children became dry while on treatment (86/400 achieved 14 dry nights on imipramine compared to 22/413 on placebo), this effect was not sustained after treatment stopped (6/192 on imipramine compared to 7/209 on placebo).

■ Simple behavioural interventions are widely used as standard first line treatment, but they require a high level of parental involvement. Currently, there is insufficient evidence to support the use of any particular intervention.

Insufficient reliable evidence was found comparing desmopressin with tricyclics or other related drugs. Likewise, there was a lack of reliable evidence comparing desmopressin or tricyclics with simple and complex behavioural interventions.

■ The use of an alarm intervention has been shown to reduce nighttime bedwetting in a majority of children both during treatment and after treatment stops. Overlearning (giving children extra fluids at bedtime after successfully becoming dry using an alarm) may reduce the relapse rate. Before embarking on alarm treatment, families need to be made aware of both the time and the high level of parental involvement necessary to attain success.

Acceptability of drugs The British National Formulary (BNF) currently suggests that drug therapy is not usually appropriate for children under seven years of age and is reserved for when alternative measures have failed.35 Fluid overload is potentially the most serious complication with desmopressin. It is associated with over-drinking at bedtime and its symptoms include headache, nausea, hyponatraemia, cerebral oedema and convulsions. Tricyclics have significant adverse effects, including cardiotoxic and hepatotoxic effects in overdose. Minor side effects related to their anticholinergic actions include postural hypotension, dry mouth, constipation, perspiration, tachycardia, nausea, lethargy and insomnia. The BNF recommends that the possible side effects of the various drugs should be considered and that any prescription should not be continued for longer than three months without stopping for a full re-assessment.35

E. Implications ■ Much of the available research on the effects of interventions used to treat nocturnal enuresis in children is of poor quality and there are few direct comparisons between different types of intervention.

6

■ Drug therapy such as desmopressin reduces the number of wet nights per week compared with placebo, but only for as long as the drug is used. However, drugs could be used as a way to reduce the frequency of wetting for a specific purpose such as nights away from home (e.g. for holidays or staying with friends). Children and their families need to be informed about possible side effects of some of the drugs. ■ Future research must be of higher methodological quality, involve comparisons between those interventions used most commonly in practice, be undertaken in appropriate settings and include follow-up periods of longer duration.

Appendix on methods The bulletin is based upon a series of systematic reviews that have been carried out by the Cochrane Incontinence Group. Full details of review methods are available on the Cochrane Library. Relevant trials were identified from the Group’s specialised register of

EFFECTIVE HEALTH CARE Treating nocturnal ensuresis in children

controlled trials which is described under the Incontinence Group’s details in The Cochrane Library. The register contains trials identified from MEDLINE, CINAHL, the Cochrane Central Register of Controlled Trials (CENTRAL) and handsearching of journals and relevant conference proceedings. In addition, the cited references from the included trials were searched. No language or other restrictions were imposed on any of these searches and non-English language papers were translated where necessary. Studies were assessed using the methods of the Cochrane Collaboration.36 All randomised or quasi-randomised trials of interventions for the treatment of non-organic nocturnal enuresis in children were included (as defined by the trialists, usually up to age 16). Two reviewers screened the studies independently for eligibility. Where the trials have been published in more than one publication, only the primary source has been referenced. Two reviewers independently assessed the quality of the eligible trials, and extracted data using a standard form. Primary outcomes of interest were: the number of wet nights per week during treatment and at follow up; the number of children who were cured during treatment (defined as achieving 14 consecutive dry nights) or who relapsed at follow up; and any adverse events. A fixed effect model was used to calculate the pooled estimates and the 95% confidence intervals.37

References 1. World Health Organisation. Nonorganic enuresis. The ICD-10 classification of mental and behavioural disorders: Clinical descriptions and diagnostic guidelines. Geneva: WHO, 1992. 2. American Psychiatric Association. Functional enuresis. Diagnostic and

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statistical manual of mental disorders. 3rd (revised) ed. Washington: American Psychiatric Association, 1980. 3. Fitzwater D, Macknin ML. Risk/benefit ratio in enuresis therapy. Clin Pediatr (Phila) 1992;31:308-10. 4. Warzak WJ. Psychosocial implications of nocturnal enuresis. Clin Pediatr (Phila) 1992;Spec No: 38-40. 5. Hagglof B, Andren O, Bergstrom E, et al. Self-esteem before and after treatment in children with nocturnal enuresis and urinary incontinence. Scand J Urol Nephrol 1997;31:79-82. 6. de Jonge GA. Epidemiology of enuresis: a survey of the literature. In: Kolvin I, MacKeith RC, Meadow SR. (eds) Bladder control and enuresis. London: William Heinemann Medical Books, 1973. 7. Krantz I, Jylkas E, Ahlberg BM, et al. On the epidemiology of nocturnal enuresis-a critical review of methods used in descriptive epidemiological studies on nocturnal enuresis. Scand J Urol Nephrol 1994;Supp.163:75-82. 8. Blackwell C. A guide to enuresis: A guide to treatment of enuresis for professionals. Bristol: ERIC, 1989. 9. Rona R, Li L, Chinn S. Determinants of nocturnal enuresis in England and Scotland in the ‘90s. Dev Med Child Neurol 1997;39:667-681. 10. Swithinbank L, Brookes S, Shepherd A, et al. The natural history of urinary symptoms during adolescence. Br J Urol 1998;81: 90-93.

15. Norgaard JP, Djurhuus JC. The pathophysiology of enuresis in children and young adults. Clin Pediatr (Phila) 1993;Spec No:5-9. 16. Rutter M, Yule W, Graham P. Enuresis and behavioural deviance. Some epidemiological considerations. In: Kolvin I, MacKeith RC, Meadow SR. (eds) Bladder control and enuresis. London: William Heinemann Medical Books, 1973. 17. Shaffer D. Enuresis. In: Rutter M, (ed) Child psychiatry: modern approaches. Oxford: Blackwell Scientific Publications, 1977. 18. Devlin JB. Prevalence and risk factors for childhood nocturnal enuresis. Ir Med J 1991;84:118-20. 19. Moffatt ME. Nocturnal enuresis: psychologic implications of treatment and nontreatment. J Pediatr 1989;4:697-704. 20. Jarvelin MR. Developmental history and neurological findings in enuretic children. Dev Med Child Neurol 1989;31:728-36. 21. Koff SA. Cure of nocturnal enuresis: why isn’t desmopressin very effective? Pediatr Nephrol 1996;10:667-70. 22. Maizels M, Gandhi K, Keating B, et al. Diagnosis and treatment for children who cannot control urination. Curr Probl Pediatr 1993;23:402-50. 23. Butler RJ, Redfern EJ, Holland P. Children’s notions about enuresis and the implications for treatment. Scand J Urol Nephrol 1994;163:39-47.

11. Bakwin H. Enuresis in twins. Am J Dis Child 1971;121:222-5.

24. Butler R, Holland P. The three systems: A conceptual way of understanding nocturnal enuresis. Scand J Urol Nephrol 2000;34: 270-277.

12. Bakwin H. The genetics of enuresis. In: Kolvin I, MacKeith RC, Meadow SR. (eds) Bladder control and enuresis. London: William Heinemann Medical Books, 1973.

25. Morgan R. Guidelines in the minimum standards of practice in the treatment of enuresis. Bristol, UK: Enuresis Resource and Information Centre, 1993.

13. Eiberg H, Berendt I, Mohr J. Assignment of dominant inherited nocturnal enuresis (ENUR1) to chromosome 13q. Nat Genet 1995;10:354-6.

26. Enuresis Resource and Information Centre. ERIC Online (Website), Date accessed: June 2003 (URL:http://www.eric.org.uk).

14. Djurhuus JC, Norgaard JP, Rittig S. Monosymptomatic bedwetting. Scand J Urol Nephrol 1992;Supp.141:7-19.

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27. Department of Health. Getting the right start: National Service Framework for Children. Emerging findings. London: Department of Health, April 2003.

28. NHS Centre for Reviews and Dissemination. A Systematic Review of the Effectiveness of Interventions for Managing Childhood Nocturnal Enuresis. CRD Report 11. York: University of York, 1997. 29. Glazener CMA, Evans JE. Simple behavioural and physical interventions for nocturnal enuresis in children. (Cochrane Review) The Cochrane Library, Issue 3. Oxford: Update Software, 2003. 30. Glazener C, Evans J. Complex behavioural interventions for nocturnal enuresis in children. (Cochrane Review) The Cochrane Library, Issue 3. Oxford: Update Software, 2003. 31. Glazener CM, Evans JH, Peto R. Alarm interventions for nocturnal enuresis in children (Cochrane Review). The Cochrane Library, Issue 3. Oxford: Update Software, 2003. 32. Glazener CMA, Evans JHC. Desmopressin for nocturnal enuresis in children. (Cochrane Review) The Cochrane Library, Issue 3. Oxford: Update Software, 2003. 33. Glazener C, Evans J, Peto R. Tricyclic and related drugs for nocturnal enuresis in children (Cochrane Review). The Cochrane Library, Issue 3. Oxford: Update Software, 2003. 34. Glazener C, Evans J. Drugs for nocturnal enuresis in children (other than desmopressin and tricyclics) (Cochrane Review). The Cochrane Library, Issue 3. Oxford: Update Software, 2003. 35. British Medical Association, Royal Pharmaceutical Society of Great Britain. British National Formulary. London: British Medical Association, Royal Pharmaceutical Society of Great Britain, 2003. 36. Clarke M, Oxman AD. Analysing and presenting results. Cochrane Reviewers Handbook 4.1.4. The Cochrane Library, Issue 3. Oxford: Update Software, 2003. 37. Berlin JA, Laird NM, Sacks HS, et al. A comparison of statistical methods for combining event rates from clinical trials. Stat Med 1989;8: 141-51.

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Effective

Health Care

This bulletin is based on systematic reviews carried out by Cathryn Glazener and Johnathan Evans of the Cochrane Incontinence Group, with additional review work carried out by Rachel Peto of the Centre for Reviews and Dissemination, University of York. The bulletin was written and produced by staff at the Centre for Reviews and Dissemination, University of York.

The Effective Health Care bulletins are based on systematic review and synthesis of research on the clinical effectiveness, cost-effectiveness and acceptability of health service interventions. This is carried out by a research team using established methodological guidelines, with advice from expert consultants for each topic. Great care is taken to ensure that the work, and the conclusions reached, fairly and accurately summarise the research findings. The University of York accepts no responsibility for any consequent damage arising from the use of Effective Health Care.

Acknowledgements Effective Health Care would like to acknowledge the helpful assistance of the following who commented on the text: ■ Mark Baker, Yorkshire Cancer Network ■ Richard Butler, East Leeds PCT ■ Penny Dobson, Enuresis Resource and Information Centre ■ Alison Evans, University of Leeds ■ Johnathan Evans, Nottingham City Hospital NHS Trust ■ Cathryn Glazener, University of Aberdeen

■ Adrian Grant, University of Aberdeen ■ Molly Haig, Enuresis Resource and Information Centre ■ Steve Holmes, Mendip PCT ■ Dee Kyle, Bradford South and West PCT ■ Colin Pollock, Regional Directorate of Public Health (Yorkshire & Humber) ■ June Rogers, Knowsley PCT ■ Stephen Singleton, Northumberland HA ■ Colin Waine, Sunderland HA ■ Sheila Wallace, University of Aberdeen

Effective Health Care Bulletins Vol. 3 1. Preventing and reducing the adverse effects of unintended teenage pregnancies 2. The prevention and treatment of obesity 3. Mental health promotion in high risk groups 4. Compression therapy for venous leg ulcers 5. Management of stable angina 6. The management of colorectal cancer

5. Antimicrobial prophylaxis in colorectal surgery 6. Deliberate self-harm

Vol. 5 1. Getting evidence into practice 2. Dental restoration: what type of filling? 3. Management of gynaeological cancers 4. Complications of diabetes I 5. Preventing the uptake of smoking in young people 6. Drug treatment for schizophrenia.

Vol. 4

Vol. 6

1. Cholesterol and CHD: screening and treatment 2. Pre-school hearing, speech, language and vision screening 3. Management of lung cancer 4. Cardiac rehabilitation

1. Complications of diabetes II 2. Promoting the initiation of breast feeding 3. Psychosocial interventions for schizophrenia 4. Management of upper gastro-intestinal cancer

5. Acute and chronic low back pain 6. Informing, communicating and sharing decisions with people who have cancer

Vol. 7 1. Effectiveness of laxatives in adults 2. Acupuncture 3. Homeopathy 4. Interventions for the management of CFS/ME 5. Improving the recognition and management of depression in primary care 6. The prevention and treatment of childhood obesity

Vol. 8 1. Inhaler devices for the treatment of asthma and COPD

Full text of previous bulletins available on our web site: www.york.ac.uk/inst/crd

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EFFECTIVE HEALTH CARE Treating nocturnal ensuresis in children

VOLUME 8 NUMBER 2

2003