PHARMAZEUTISCHE WISSENSCHAFT Anne-Kristina Frobel und Stephanie Läer Klinische Pharmazie und Pharmakotherapie Heinrich-Heine-Universität, Düsseldorf Besonderheiten der Pharmakotherapie bei Kindern Lektorat: Frau Apothekerin Daniela Hundelshausen, Brunnen-Apotheke, Hallenberg Herr Apotheker Dr. Jürgen Dittrich, Rathaus-Apotheke, Grünwald ABSTRACT: The medical care of the
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Labdominguez.comEvaluation and Treatment of Enuresis
KALYANAKRISHNAN RAMAKRISHNAN, MD, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
Enuresis is defined as repeated, spontaneous voiding of urine during sleep in a child five years or older. It affects 5 to
7 million children in the United States. Primary nocturnal enuresis is caused by a disparity between bladder capac-
ity and nocturnal urine production and failure of the child to awaken in response to a full bladder. Less commonly,
enuresis is secondary to a medical, psychological, or behavioral problem. A diagnosis usually can be made with a his-
tory focusing on enuresis and a physical examination followed by urinalysis. Imaging and urodynamic studies gener-
ally are not needed unless specifically indicated (e.g., to exclude suspected neurologic or urologic disease). Primary
nocturnal enuresis almost always resolves spontaneously over time. Treatment should be delayed until the child is
able and willing to adhere to the treatment program; medications are rarely indicated in children younger than seven
years. If the condition is not distressing to the child, treatment is not needed. However, parents should be reassured
about their child’s physical and emotional health and counseled about eliminating guilt, shame, and punishment.
Enuresis alarms are effective in children with primary nocturnal enuresis and should be considered for older, moti-
vated children from cooperative families when behavioral measures are unsuccessful. Desmopressin is most effective
in children with nocturnal polyuria and normal bladder capacity. Patients respond to desmopressin more quickly
than to alarm systems. Combined treatment is effective for resistant cases. (Am Fam Physician. 2008;78(4):489-496,
498. Copyright 2008 American Academy of Family Physicians.)
▲ Patient information:
A handout on enuresis,
written by the author of
this article, is provided on
Enuresis is defined as repeated, spon- uninhibited bladder contractions before taneous voiding of urine during sleep voiding (i.e., detrusor-dependent enuresis).9 in a child five years or older.1 Enure- A variety of medical and psychological dis- sis may be classified as primary or orders are associated with secondary enure- secondary, and monosymptomatic (uncom- sis (Table 3 2,6). Underlying psychological plicated) or nonmonosymptomatic (i.e., con- stressors are suspected when a child who has comitant lower urinary tract symptoms are not had enuresis develops the condition dur-present). Table 1 summarizes the types of ing a period of stress.2 In one study, 11 per-enuresis.1,2 Children with primary nocturnal cent of girls who had been sexually abused enuresis are monosymptomatic, have no lower presented with enuresis.12 However, there urinary tract symptoms other than nocturia, is little, if any, association between sexual and have no history of bladder dysfunction.1 Nocturnal enuresis is three times more Genetic influences on nocturnal enure- common than daytime wetting and affects 6.7 sis are heterogenous and complex.10 A his-percent of younger children and 2.8 percent tory of enuresis in parents increases the risk. of older children.3,4 It occurs three times more When one or both parents have a history of often in boys.5 Secondary causes account for enuresis, the incidence in children is 44 and less than 25 percent of cases.6,7 77 percent, respectively, compared with a 15 percent incidence in children whose parents Pathophysiology
do not have a history of enuresis.2 If one twin Primary nocturnal enuresis is caused by has enuresis, the other twin usually is also a disparity between bladder capacity and affected.10,11 An autosomal dominant mode of nocturnal urine production and the child’s transmission with high penetrance is present failure to awaken in response to a full in some families, and many possible locations bladder.8 Factors associated with enuresis for the responsible genes (in chromosomes 8, (Table 2) include nocturnal polyuria, detru- sor instability, and an abnormally deep sleep
pattern.2,8-12 A small subgroup of children Clinical Features
with primary nocturnal enuresis have little or A cross-sectional study comparing patients
no arousal to bladder distention and exhibit presenting with primary and secondary
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SORT: KEY RECOMMENDATIONS FOR PRACTICE
Treatment for primary nocturnal enuresis begins with educating the child and parents about the condition; daytime symptoms should be actively identified and managed before addressing primary nocturnal enuresis; and, if identified, secondary causes should be treated appropriately.
If primary nocturnal enuresis is not distressing to the child, treatment is unnecessary, although parents should be reassured about their child’s physical and emotional health and counseled about eliminating guilt, shame, and punishment.
An enuresis alarm is effective in children with monosymptomatic nocturnal enuresis; overlearning (i.e., encouraging the child to drink extra fluids before bedtime to improve bladder capacity) should be added when continence has been achieved for 14 consecutive nights.
Dry-bed training and bladder training alone are not recommended to treat primary nocturnal enuresis.
Anticholinergics are useful in children with urgency, restricted bladder capacity from detrusor hyperactivity at night, and combined daytime wetting and nocturnal incontinence and in children who do not respond to desmopressin (DDAVP).
Desmopressin is most effective in children who have monosymptomatic enuresis with nocturnal polyuria A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, see http://www.aafp.
org/afpsort.xml. Table 1. Types of Enuresis
Table 2. Factors Associated with
and Contributing to Enuresis
Decreased functional bladder capacity; inability Lack of arousal to bladder distention and uninhibited bladder contractions (occurs in a Increased incidence of enuresis in children if one or both parents have a history of enuresis; in the case of twins, both children are usual y affected Delay in central nervous system maturation and in the development of language and motor skil s Decreased nocturnal secretion of antidiuretic hormone causes nocturnal polyuria; blunted Not common with primary nocturnal enuresis; response to stress or trauma (e.g., parental divorce, sexual abuse, trauma at school, Enuresis occurs in all stages of sleep; an NOTE: Enuresis is the repeated, spontaneous voiding of urine during abnormal y deep sleep pattern may occur in sleep in a child five years or older. *—Standing on the tiptoes, crossing the legs, or squatting with the heel pressed into the perineum (“curtsy sign”). NOTE: Several factors may contribute to primary nocturnal enuresis. Information from references 1 and 2. Information from references 2, and 8 through 12. nocturnal enuresis showed that frequency, urgency, secondary nocturnal enuresis and in nearly 75 percent nocturia, constipation, and daytime wetting are com- of children with primary nocturnal enuresis, is also mon in both forms of enuresis.13 Constipation, which associated with daytime wetting.13 A more recent pro-occurs in more than 50 percent of children with spective cross-sectional study of children with primary 490 American Family Physician
Volume 78, Number 4 ◆ August 15, 2008 Enuresis
Table 3. Precipitating Conditions Associated
with Secondary Enuresis
Urinalysis and urine culture help detect infection. Select laboratory tests are useful in diagnosing causes of secondary enuresis (e.g., elevated serum glucose level from diabetes, elevated blood urea nitrogen and creatinine levels from chronic renal failure, low serum thyroid-stimulating hormone level from hyperthyroid- ism). Imaging and urodynamic studies are reserved for Information from references 2 and 6. children with significant daytime symptoms, history or diagnosis of urinary tract infections, features suggesting nocturnal enuresis showed that more than one third of structural renal abnormalities, or refractory cases.2,8patients have constipation.14 Behavioral problems are uncommon in children with Treatment of Primary Nocturnal Enuresis
primary nocturnal enuresis, especially those older than Treatment of primary nocturnal enuresis (Figure 1 and 10 years. These problems are more common in children Table 5 2,8,17,19-35) should begin with educating the child with daytime wetting and over seven times more com- and parents about the condition. The family should mon in children with secondary enuresis.15 Behavioral be reassured that primary nocturnal enuresis usually problems include depression, anxiety, social phobias, resolves spontaneously (15 percent annual cure rate).17 conduct disorders, and attention-deficit/hyperactivity Secondary causes that were identified with the history, disorder (ADHD). The association with ADHD is more examination, or laboratory testing should be treated. pronounced in older children (nine to 12 years of age); Simple behavioral interventions are first-line treatment children with ADHD are three times more likely to have approaches. Arousal alarm systems and pharmacother-persistent voiding problems.16 Children with enuresis are apy should be considered in older children who have more likely than other children to have subclinical psy- greater social pressures and low self-esteem. chological symptoms (e.g., inferiority complex, shame, Medication should be initiated in children seven years irritability, timidity, impatience, isolation). Parental stress and older only if nonpharmacologic measures fail. Chil-(e.g., emotional, social, and financial stress; intolerance; dren who do not respond to one or more measures may frustration) may also occur.8 benefit from combined treatment strategies (e.g., com-bining nonpharmacologic and pharmacologic treatment Evaluation
or multiple pharmacologic therapies). Children with per- Most children with primary nocturnal enuresis require sistent enuresis should be referred to a subspecialist. Pres-only an enuresis-focused history, physical examina- ence of daytime wetting or abnormal voiding, straining tion, and urinalysis before initiation of treatment; or poor stream, genital abnormalities, or a history of uri-
imaging and urodynamic studies are rarely needed nary tract infections also indicates the need for referral.2
(Table 41,2,6,8,10,11,17). The history should include the onset,
duration, and severity of enuresis; presence of daytime NONPhARMACOlOgIC OPTIONS
wetting, constipation, genitourinary symptoms, and If primary nocturnal enuresis is not distressing to the
neurologic symptoms; family history of enuresis; patient child, treatment is not needed. However, parents should
medical and psychosocial history; and details of previous be reassured about their child’s physical and emotional
treatment. The parents and child should be interviewed.2 health and counseled about eliminating guilt, shame, and
A two-week baseline record of the enuresis pattern (blad-
punishment.2,19 Treatment of primary nocturnal enure- der diary) is helpful in the assessment of enuresis sever- sis should be delayed until the child is able and willing to adhere to the treatment program and is rarely indicated in The physical examination should include evaluation children younger than seven years. It may take months for of the ears, nose, throat, abdomen, spine, genitalia, and a treatment program to be successful; therefore, the child rectum and a focused neurologic examination. In chil- must be highly motivated. Daytime symptoms should be dren with secondary or persistent enuresis, the possibil- actively identified and managed before addressing primary ity of sexual abuse must be considered. Signs suggestive nocturnal enuresis.17 Treatment is considered success-of sexual abuse include bruising in areas that are typi- ful when the child achieves continence for 14 consecutive cally protected (e.g., buttocks, back, trunk, inner thighs, nights within a 16-week period. Nonresponse to treatment cheeks, neck); multiple bruises; and patterned bruises is defined as less than a 50 percent decrease in enuresis; a (e.g., handprints, belt buckle, bite marks).18 50 to 90 percent decrease suggests a partial response.1 August 15, 2008 ◆ Volume 78, Number 4 American Family Physician 491
Table 4. Evaluation of Children with Enuresis
Age at onset of enuresis, duration and severity of enuresis, duration of continence (enuresis is not diagnosed in children younger than five years; recurrence after at least six months of urinary continence suggests secondary enuresis)1,2 Presence of lower urinary tract symptoms* (symptoms other than nocturia suggest nonmonosymptomatic History of medical il ness (e.g., diabetes mel itus, sleep apnea) may suggest nonmonosymptomatic enuresis6Psychosocial history (psychological disturbances are present in one third of patients with secondary enuresis)8Family history of enuresis (the condition is more common in patients with a family history; in the case of twins, both children are usual y affected)2,10,11 Fluid-intake diary, bladder and stooling diary, frequency/volume chart (records help assess constipation, enuresis severity, and treatment response)2,8 Investigation and treatment history Red flags: dysuria, genital or rectal pain or discharge, straining to urinate, combined diurnal and nocturnal frequency with enuresis (suggests nonmonosymptomatic enuresis) Ears, nose, and throat examination to detect adenotonsil ar hypertrophyAbdominal examination to detect enlarged bladder or kidneys and fecal masses indicating encopresisGenital examination to detect hypospadias or epispadias, meatal stenosis, ectopic ureter, and labial adhesionsRectal examination to evaluate perianal and perineal sensation and rectal sphincter tone and to detect Focused neurologic evaluation, including gait, muscle tone, strength, and perineal sensationRed flags (indicate need for further investigation): adenotonsil ar hypertrophy, spinal pathology (deformity, sacral dimple or hair tuft suggesting underlying spinal dysraphism), motor sensory loss and abnormal tendon reflexes in the lower limbs, enlarged bladder or kidneys, abnormal gait, signs of sexual abuse Detection of urinary tract infection, diabetes mel itus, diabetes insipidus Blood urea nitrogen and serum creatinine levels to detect chronic renal failure, serum glucose levels to detect diabetes, hemoglobin electrophoresis to detect sickle cell disease, serum thyroid-stimulating hormone level to detect hyperthyroidism Renal and bladder ultrasonography and voiding cystourethrography for a suspected structural abnormality, significant daytime wetting, or recurrent urinary infections to detect vesicoureteral reflux Magnetic resonance imaging of the lumbosacral spine for suspected spinal dysraphism or abnormal Measurement of residual urine and cystometry to evaluate bladder dysfunction (dysfunctional voiding) *—Nocturia, urgency, daytime wetting, squatting, incontinence, constipation.
†—Required only if secondary causes are suspected, red flags are detected on history or examination, or the patient does not respond to standard treatment.
Information from references 1, 2, 6, 8, 10, 11, and 17. Motivational therapy includes reassurance, emo- are used, failure to achieve dry nights may worsen the tional support, eliminating guilt, and encouraging child’s self-esteem.19the child to take responsibility for the enuresis (i.e., Enuresis alarms (bells or buzzers) triggered by a mois- although the child did not cause the condition, he or ture sensor in the bed pad or pajamas have long-term she has a role in treating it).20 Simple behavioral inter- effectiveness2,19,24 Alarms condition children to awaken ventions include awakening the child to void at times or contract their pelvic muscles. Most children require usually associated with bed-wetting; positive reinforce- six to 16 weeks of treatment. Enuresis resolves in nearly ment for desired behavior (e.g., star or sticker charts two thirds of children during alarm use, and nearly one for rewarding periods of continence); bladder training; half of children who continue its use remain dry.24 No and minimizing fluid and caffeine intake before bed- alarm system is superior to another.21 Sleep disruption time. These methods are associated with significantly is a problem with alarm use. Factors that predict a good fewer wet nights, higher cure rates, and lower relapse response to enuresis alarms include a cooperative family, rates compared with control groups. However, behav- no coexisting emotional and behavioral problems, small ioral interventions have higher nonadherence rates bladder capacity, and frequent bed-wetting (four or more and require significant parental involvement.21,22 Tak- wet nights per week).8 Enuresis alarms should be consid- ing the child to the bathroom during the night is labor ered in older, motivated children from cooperative fami-intensive and can frustrate parents. If reward systems lies when behavioral measures are unsuccessful.17,19 492 American Family Physician
Volume 78, Number 4 ◆ August 15, 2008 Enuresis
Evaluation and Treatment of Enuresis
Complete enuresis-specific history Perform physical examination (evaluation of ears, nose, throat, abdomen, spine, genitalia, and rectum and a focused neurologic examination) Look for red flags*Perform urinalysis; obtain urine culture, if indicated, based on urinalysis Diurnal incontinence or nonmonosymptomatic enuresis (voiding dysfunction, underlying medical condition) Perform imaging or urodynamic studies, if indicatedSee Table 4 for more information about the Parental and patient education and reassurance Nonpharmacologic (behavioral) measures† Oxybutynin (Ditropan)Combination treatment‡Subspecialist referral *—Red flags from the patient history include dysuria, genital or rectal pain or discharge, straining to urinate, combined diurnal and nocturnal frequency with enuresis, snoring, and sleep apnea. Red flags from the examination include adenotonsil ar hypertrophy; spinal pathology (deformity, sacral dimple, hair tuft, or nevus); motor sensory loss and abnormal tendon reflexes in the lower limbs; enlarged bladder or kidneys; and abnormal gait.
†—Nonpharmacologic measures include fluid restriction, motivation, bladder training, dry-bed training, biofeedback, and enuresis alarms.
‡—Combining nonpharmacologic measures with medication or using more than one medication may lead to better response and lower the risk of relapse, especial y in patients with resistant cases. Figure 1. Algorithm for the evaluation and treatment of children with enuresis.
Combining enuresis alarms with other behavioral or two to three hours after the child goes to sleep is effec- modalities enhances treatment success. Adding over- tive in 62 to 77 percent of children. However, relapse learning (i.e., encouraging children to drink extra fluids rates three months after completion of treatment are the before bedtime to improve bladder capacity) when conti- nence has been achieved for 14 consecutive nights reduces Full-spectrum home training includes behavioral relapse rates.24 Adding dry-bed training (i.e., awakening interventions such as encouraging the child to remove children at specified intervals until they learn to awaken soiled sheets and remake the bed, overlearning, dry-on their own when necessary 17) is effective in 75 percent bed training, and bladder training. A systematic review of children and reduces relapse rates compared with the showed that these measures led to minimal improvement use of an enuresis alarm alone.36 Combining an enuresis when used alone; however, when used with an enuresis alarm with arousal training (i.e., rewarding children for alarm, they reduced relapse rates.23awakening in response to the alarm) is effective in more than 90 percent of children.8 PhARMACOlOgIC OPTIONS
An alarm clock is a simple, inexpensive, safe, and mod- Pharmacologic therapies are not curative, but they estly effective alternative to an enuresis alarm and does decrease the frequency of enuresis or temporarily resolve not require bed-wetting to evoke a conditioned response. symptoms over time until spontaneous resolution Using the alarm clock to awaken the child for voiding occurs. Options include anticholinergic agents (oxy-when the bladder is full, but before incontinence occurs, butynin [Ditropan], hyoscyamine [Levsin]); tricyclic August 15, 2008 ◆ Volume 78, Number 4 American Family Physician 493
Table 5. Treatment Options for Enuresis
emotional support, eliminates guilt, rewards continence (e.g., star or sticker charts) Constipation: 73 percent effectiveDaytime wetting: 58 percent Pharmacologic†
Oral imipramine (Tofranil),
intoxication, al ergic reaction, hyponatremia, anorexia, nausea, visual disturbance, bad taste in the mouth NOTE: Children who do not respond to one or more measures may benefit from combined treatment strategies (e.g., combining nonpharmacologic and pharmacologic treatment or multiple pharmacologic therapies). *—General y first-line treatments that should be attempted before pharmacologic therapy; treatments may be combined; requires significant paren-tal involvement.
†—Of these therapies, only imipramine and oral desmopressin have been approved by the U.S. Food and Drug Administration for the treatment of enuresis in children. Indicated in children seven years and older. Information from references 2, 8, 17, and 19 through 35. antidepressants (imipramine [Tofranil], desipramine Tricyclic antidepressants reduce bed-wetting by one [Norpramin]); and desmopressin (DDAVP). Of these wet night per week during treatment. Imipramine doses therapies, only imipramine and oral desmopressin have range from 25 mg for children older than six years (weigh-been approved by the U.S. Food and Drug Administra- ing 20 to 25 kg [44 lb, 1 oz to 55 lb, 2 oz]) to 50 to 75 mg tion for the treatment of enuresis in children.
for children older than 11 years. Some recommendations 494 American Family Physician
Volume 78, Number 4 ◆ August 15, 2008 Enuresis
advise limiting the treatment period to three months Combining desmopressin therapy with an enuresis (including gradual withdrawal).19 Imipramine, 25 mg, alarm improves the response rate and reduces relapse.33should be taken orally one hour before bedtime. If the Adverse effects from desmopressin use occur in 5 per- response is not satisfactory after one or two weeks, the cent of patients. Intranasal use may cause nasal conges-dose is increased to 50 mg in children seven to 12 years tion, epistaxis, sore throat, cough, or headaches. Systemic of age and up to 75 mg in older children.20 Most children adverse effects from intranasal or oral use are rare and relapse after discontinuing imipramine treatment.26 include allergic reactions (e.g., rash; swelling of the face, Parents should be warned about the potentially seri- lips, or tongue), anorexia, nausea, abdominal cramps, ous, dose-related adverse effects of tricyclic antidepres- visual disturbances, and a bad taste in the mouth. Hypona- sant use.26 Drowsiness, lethargy, agitation, depression, tremia and water intoxication–induced seizures and coma sleep disturbance, and gastrointestinal upset may occur. are also rare, but more common after intranasal use.34 A Rare adverse effects include seizures, cardiac arrhyth- systematic review suggests that the risk of water intoxica- mias, and death from accidental overdose.26,27 Pretreat- tion can be minimized with careful monitoring during ment electrocardiography to identify underlying rhythm initiation of desmopressin therapy; supervised adminis-disorders is recommended.2 tration to minimize the risk of overdose; fluid restriction; Anticholinergics (e.g., oxybutynin, 2.5 to 5 mg three prompt assessment for hyponatremia if nausea, vomiting, times daily) decrease detrusor tone, frequency, and and headache occur; and oral administration.34,35
urgency and improve bladder capacity. Anticholinergic
therapy may be used in children with primary nocturnal Treatment of Secondary and
enuresis and daytime wetting (restricted bladder capacity Nonmonosymptomatic Enuresis
caused by hyperactive detrusor muscle) and in patients If no cause for nocturnal enuresis is evident, primary
who do not respond to desmopressin.8,17,28 Adverse effects nocturnal enuresis treatment options are appropri-
include dry mouth, blurred vision, headache, nausea, ate. Most children with encopresis-associated enuresis
dizziness, gastrointestinal upset, and tachycardia.29
and daytime wetting respond to disimpaction, preven- Desmopressin, an analogue of vasopressin, reduces tion of reaccumulation of stools, and bowel retraining urine volume by reabsorbing water from the distal con- (decreases daytime wetting in 89 percent of patients and voluted and collecting tubules. Sixty to 70 percent of chil- nocturnal enuresis in 63 percent of patients).38 dren respond to treatment, although 80 percent relapse A history of snoring, mouth breathing, behavioral after discontinuing therapy.2,8,30 Desmopressin is recom- problems, and daytime somnolence in patients with mended if the family is unwilling or unable to adhere to enlarged tonsils or adenoids on examination may sug-nonpharmacologic measures. The drug is most effective gest obstructive sleep apnea. Surgical correction of in children eight years and older who have monosymp- airway obstruction in these patients improves or cures tomatic enuresis with nocturnal polyuria, normal blad- nocturnal enuresis and daytime wetting.39 der capacity, and less frequent bed-wetting.31 Individual psychotherapy, crisis intervention, and Desmopressin is available as an oral tablet (0.2 mg) family therapy are effective measures for psychogeni- or as a nasal spray (10 mcg per spray); its duration of cally induced enuresis.2 Children with dysfunctional action is 12 hours.2 Initial treatment is usually one tablet voiding have abnormal urine flow patterns on cystom-or one spray every night; the dosage is increased weekly etry, a large amount of post-void residual urine, and a to 0.6 mg or 40 mcg daily. Desmopressin therapy is com- normal upper urinary tract on imaging and benefit from bined with fluid restriction (less than 240 mL on nights a voiding regimen. Biofeedback is effective for moti-when the drug is administered) and voiding before bed- vated children with primary nocturnal enuresis and time. Equivalent oral and intranasal doses have simi- dysfunctional voiding.25 Biofeedback improves noctur- lar potency.30 Another option is rapid titration upward nal enuresis, daytime wetting, constipation, frequency, until continence is achieved within one to three days.32 urgency, voiding patterns, and bladder hyperactivity for The lowest effective dose of desmopressin should be up to two years after completion of therapy.25used. Maintenance therapy of at least four to six weeks Children with urge incontinence, normal urine flow, and a slow stepwise dose reduction over six to seven small bladder capacity on urodynamic testing, and nor-months decrease relapse rates after discontinuation of mal imaging results benefit from anticholinergic ther-therapy.32 apy.28 These medications may also be useful in children Adding oxybutynin to desmopressin therapy increases with both daytime and nocturnal incontinence and in the response rate in children with daytime wetting.32 children who do not respond to desmopressin.8,17,28 August 15, 2008 ◆ Volume 78, Number 4 American Family Physician 495
17. Bedwetting. Paediatric Society of New Zealand. Best practice evidence The Author
based guideline. Nocturnal enuresis. http://www.paediatrics.org.nz/documents/2005%20documents%20denise/guidelines/Enuresis%20g KAlyAnAKrishnAn rAmAKrishnAn, mD, is an associate professor uideline%20final%20endorsed.pdf. Accessed November 26, 2007.
in the Department of Family and Preventive medicine at the University 18. Swerdlin A, Berkowitz C, Craft N. Cutaneous signs of child abuse. J Am of Oklahoma health sciences Center, Oklahoma City. Dr. ramakrishnan Acad Dermatol. 2007;57(3):371-392.
received his medical degree and his master’s degree in surgery from the 19. Canadian Paediatric Society. Community Paediatrics Committee. Man- Jawaharlal institute of Postgraduate medical Education and research, agement of primary nocturnal enuresis. Paediatrics & Child Health. Pondicherry, india. he completed a family practice residency at the Uni- versity of Oklahoma health sciences Center.
20. Cendron M. Primary nocturnal enuresis: current concepts. Am Fam Phy- Address correspondence to Kalyanakrishnan Ramakrishnan, MD, Uni- sician. 1999;59(5):1205-1214, 1219-1220.
versity of Oklahoma Health Sciences Center, Dept. of Family and Preven- 21. Glazener CM, Evans JH, Peto RE. Treating nocturnal enuresis in chil- tive Medicine, 900 NE 10th St., Oklahoma City, OK 73104 (e-mail: kramak dren: review of evidence. J Wound Ostomy Continence Nurs. 2004; [email protected]). Reprints are not available from the author. 22. Glazener CM, Evans JH. Simple behavioural and physical interventions Author disclosure: nothing to disclose.
for nocturnal enuresis in children. Cochrane Database Syst Rev. 2004; (2):CD003637.
23. Glazener CM, Evans JH, Peto RE. Complex behavioural and educational interventions for nocturnal enuresis in children. Cochrane Database Syst 1. Nevéus T, von Gontard A, Hoebeke P, et al. The standardization of ter- minology of lower urinary tract function in children and adolescents: 24. Glazener CM, Evans JH, Peto RE. Alarm interventions for nocturnal report from the Standardisation Committee of the International Chil- enuresis in children. Cochrane Database Syst Rev. 2005;(2):CD002911.
dren’s Continence Society. J Urol. 2006;176(1):314-324.
25. Yagci S, Kibar Y, Akay O, et al. The effect of biofeedback treatment on 2. Fritz G, Rockney R, Bernet W, et al. Practice parameter for the assess- voiding and urodynamic parameters in children with voiding dysfunc- ment and treatment of children and adolescents with enuresis. J Am tion. J Urol. 2005;174(5):1994-1997.
Acad Child Adolesc Psychiatry. 2004;43(12):1540-1550.
26. Glazener CM, Evans JH, Peto RE. Tricyclic and related drugs for nocturnal 3. Stein MA, Mendelsohn J, Obermeyer WH, Amromin J, Benca R. Sleep enuresis in children. Cochrane Database Syst Rev. 2003;(3):CD002117.
and behavior problems in school-aged children. Pediatrics. 2001;107 27. Evans JH. Evidence based management of nocturnal enuresis [published correction appears in BMJ. 2002;324(7329):98]. BMJ. 2001;323 4. Bower WF, Moore KH, Shepherd RB, Adams RD. The epidemiology of childhood enuresis in Australia. Br J Urol. 1996;78(4):602-606.
28. Nevéus T. Oxybutynin, desmopressin and enuresis. J Urol. 2001; 5. Mil er K. Concomitant nonpharmacologic therapy in the treatment of primary nocturnal enuresis. Clin Pediatr (Phila). 1993;Spec No:32-37.
29. Glazener CM, Evans JH, Peto RE. Drugs for nocturnal enuresis in children 6. Robson WL, Leung AK. Secondary nocturnal enuresis. Clin Pediatr (other than desmopressin and tricyclics). Cochrane Database Syst Rev. 7. Chiozza ML, Bernardinel i L, Caione P, et al. An Italian epidemiological 30. Glazener CM, Evans JH. Desmopressin for nocturnal enuresis in chil- multicentre study of nocturnal enuresis. Br J Urol. 1998;(81 suppl 3): dren. Cochrane Database Syst Rev. 2002;(3):CD002112.
31. Kruse S, Hel ström AL, Hanson E, Hjälmås K, Sil én U. Treatment of pri- 8. Hjalmas K, Arnold T, Bower W, et al. Nocturnal enuresis: an interna- mary monosymptomatic nocturnal enuresis with desmopressin: predic- tional evidence based management strategy. J Urol. 2004;171(6 pt 2): tive factors. BJU Int. 2001;88(6):572-576.
32. Riccabona M, Oswald J, Glauninger P. Long-term use and tapered dose 9. Nevéus T. The role of sleep and arousal in nocturnal enuresis. Acta Pae- reduction of intranasal desmopressin in the treatment of enuretic chil- diatr. 2003;92(10):1118-1123.
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10. von Gontard A, Schaumburg H, Hol mann E, Eiberg H, Rittig S. The 33. Bradbury MG, Meadow SR. Combined treatment with enure- genetics of enuresis: a review. J Urol. 2001;166(6):2438-2443.
sis alarm and desmopressin for nocturnal enuresis. Acta Paediatr. 11. Hublin C, Kaprio J, Partinen M, Koskenvuo M. Nocturnal enuresis in a nationwide twin cohort. Sleep. 1998;21(6):579-585.
34. Robson WL, Leung AK, Norgaard JP. The comparative safety of oral ver- 12. Center for Health Information Management and Evaluation. Missouri sus intranasal desmopressin for the treatment of children with noctur- monthly vital statistics. Sexual abuse and the SAFE-CARE data. Jefferson nal enuresis. J Urol. 2007;178(1):24-30.
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496 American Family Physician
Volume 78, Number 4 ◆ August 15, 2008
A LA MEMORIA DE MI FRATERNAR Y COLABORADOR EL ILUSTRE MÚSICO TOLEDANO EMILIO CEBRIÁN RUIZ Emilio, hay un vacio junto a mi. Tú que fuiste Con tu alegre sonrisa mi mejor compañero, Me dejaste de pronto… Y ante la vida, triste, A veces el retorno de tu canción espero. Que como sortilegio del enigma fulgura… ¡Qué días los que unimos nuestras Artes! Tu Cantaba las estr