MARF CONTEST WINNER
PRIMARY NOCTURNAL ENURESIS

Treatment Of Primary Nocturnal Enuresis
With Hand Therapy: A Randomized, Double-Blind,
Placebo-Controlled Trial
Roberto Jodorkovsky, MD

ABSTRACT  
Background     Despite its high rate of resolution and response to placebo, primary nocturnal enuresis often requires treatment in childhood, particularly due to the psychological complications. Reports on the efficacy of acupuncture in primary nocturnal enuresis have been favorable, but limited by study design.
Objective       To examine the efficacy and safety of Korean Hand Therapy (KHT) acupuncture for primary nocturnal enuresis in children.
Design, Setting, and Patients     A randomized, double-blind, placebo-controlled, crossover trial of KHT for 5 weeks in 26 children (ages 5-13 years) enrolled from the author's pediatric practice. Eleven children were randomized to group 1 and 15 to group 2.
Intervention     Points to activate the bladder, kidney, and cerebral function were stimulated with an E-beam machine during active intervention. During the placebo period, patients were connected to the machine with nonfunctioning cords.
Main Outcome Measures     Percentage of completely dry nights for each time period (baseline, study period 1, and study period 2 following crossover). Secondary outcomes were cure rate at 3 months and reported adverse effects.
Results     Improvement from baseline to study period 1 was reported, regardless of the functional status of the cord (real cords, 91%, P = .002, fake cords, 80%, P<.001). The degree of improvement was higher in the children who started the treatments with real cords (24 vs 10 percentage point improvement, P = .07). Improvement was also noted during the study period 2, regardless of the status of the cords. However, the improvement was statistically significant for the children who switched from fake to real cords (67%, P = .02). Of all the children, 53% were cured 3 months after completing the study. There were no reported adverse effects.
Conclusions      This study suggests that acupuncture is a safe and effective treatment option for primary nocturnal enuresis. Hand therapy appears to exert its beneficial effect through both placebo and direct effects. The E-beam machine offers a unique opportunity to conduct clinical research in acupuncture using randomized, double-blind, placebo-controlled designs. 

KEY WORDS
Primary Nocturnal Enuresis, Acupuncture, Randomized Controlled Trial, Placebo Effect, Bedwetting

INTRODUCTION
nuresis is defined as the involuntary voiding of urine at an age when bladder control should be developed.1,2 Primary nocturnal enuresis (bedwetting) occurs predominantly during sleep and is present since birth.1,3 It is common in childhood, affecting 15%-20% of children at age 5 years. The incidence gradually decreases to 2%-3% at ages 12-14 years.1,4 Primary nocturnal enuresis is rarely caused by potentially serious organic pathologies. Its etiology is probably multifactorial and is still unclear, although genetic factors seem to play the most important role. Other factors implicated have included bladder capacity, sleep characteristics, and central nervous system differences.3,5 Although bedwetting generally resolves with increasing age at a rate of 15% per year, secondary psychological complications associated with shame, guilt, and low self-esteem justify treatment in many children.6-9

Treatment of enuresis can include behavioral conditioning (most commonly the alarm system) and pharmacological modalities (for example, desmopressin, imipramine, oxybutynine). These treatments remain controversial because: outcome studies have shown success rates ranging widely from 20%-75%, varying rates of post-treatment relapse, few but potentially serious adverse effects from medication, and patients' resistance to use of sound mechanical devices.1,3-5,9-14

Recent reports on the efficacy of acupuncture in enuresis have been encouraging, with response rates between 40% and 86% after 6 months to 1 year of treatment, low relapse rates, and minimal adverse effects.15-17 However, the validity of these data is limited by the lack of double-blind, placebo-controlled study design. This constraint is particularly relevant when studying nocturnal enuresis because of this condition's high spontaneous rate of resolution and response to placebo. Several studies have suggested that up to 25% of children with primary nocturnal enuresis respond to any type of intervention through a general placebo effect.1-3,9

Korean Hand Therapy (KHT) is a reflex microsystem in which the whole body is represented in a holographic fashion.18 Body zonal representations have been thoroughly mapped, as have internal organs, micromeridians, and micropoints corresponding to body Chinese meridians and points. KHT has been reported to be safe and effective for a variety of pediatric conditions. The stimulation of hand points can be performed with needles, metals, magnets, or low-intensity electrical-magnetic current (E-beam machine), separately or in combination.18-21

The E-beam machine is suitable for double-blind studies because: it discharges low electromagnetic current that is imperceptible to patients (0-200 UA); delivery of the current is accomplished through 2 cords attached gently to 2 hand points which circulate electricity from negative to positive poles;  the control group is treated with nonfunctioning cords (wires internally sectioned);  the treated group receives acupuncture point stimulation through intact cords;  the cords are externally similar so both the investigator and patients are blind to their functional status; and patients and acupuncturists are aware of the sound emitted by the machine only when it is activated.

Using the E-beam machine to activate hand points, my intent was to assess the efficacy and safety of hand acupuncture to treat primary nocturnal enuresis using a randomized, double-blind, placebo-controlled design.

METHODS
From my general pediatrics private practice, 33 children were enrolled. All children met the diagnostic criteria of primary nocturnal enuresis described earlier, were at least 5-years-old, and reported experiencing nocturnal enuresis an average of at least 3 nights each week.

None of the children's enuresis was thought to be secondary to medical or surgical causes on the basis of their histories, physical examinations, and any laboratory investigations. Previous, unsuccessful traditional treatment of enuresis was not an exclusion criterion.

The patients received no other treatment for enuresis while undergoing the research. Informed consent was obtained from the subjects' parents, and the nature of the research was explained to the children.  Baseline information collected prior to the study included general demographic characteristics, family history of enuresis, and average number of wet nights per week. The latter information was drawn from a 2-week pretreatment record-keeping observation period.
 

TABLE 1. Children's Characteristics and Outcomes
Child No.	Group*	Age, y	Sex	Baseline	Study Period 1		Study Period 2
				Dry Nights, %	No. of Days	Dry Nights, %	No. of Days	Dry Nights,
								%	Cured†
1	1	6	M	7	16	62	18	66	Yes
2	1	9	M	42	17	82	19	52	Yes
3	1	7	M	42	18	83	17	94	Yes
4	1	13	M	42	29	55	18	83	Yes
5	1	9	M	28	15	40	17	82	Yes
6	1	5.5	M	42	17	94	17	76	Yes
7	2	6	M	50	15	60	17	76	Yes
8	2	7	M	0	19	0	16	0	No
9	2	9	M	7	16	12	21	14	No
10	2	8	M	0	20	0	17	0	No
11	2	7	M	0	14	14	19	0	No
12	2	7	M	0	16	37	21	47	Yes
13	2	7	M	0	25	4	19	74	Yes
14	2	7	M	42	16	62	18	83	Yes
15	1	9.5	F	0	19	0	20	0	No
16	1	10	F	0	19	18	22	50	No
17	1	6	F	50	19	74	24	95	Yes
18	1	8	F	7	22	14	16	12	No
19	1	10	F	0	15	26	17	0	No
20	2	6	F	7	26	8	21	14	No
21	2	6	F	42	19	52	21	86	Yes
22	2	5	F	7	19	15	18	5	No
23	2	7	F	0	18	50	36	70	Yes
24	2	6	F	7	15	20	24	58	No
25	2	9	F	14	33	12	16	75	Yes
26	2	7	F	0	14	50	17	41	No
*Group 1 patients began the study with functional cords and then crossed over; group 2 patients began the study with fake cords and then crossed over.
†Patients who remained dry for a minimum of 90% of the nights were considered cured.

Patients were randomized to begin acupuncture with the E-beam machine (Sooji E-Beam, Korea), using either real or fake cords. Treatments were performed 2 times weekly. Each patient served as his or her own control: after completing 5 consecutive treatments with the starting cord, patients received another 5 consecutive treatments with the other cord. I remained blinded to the process of randomization and functional status of the cords; an independent observer randomized the patients and decoded the cords at the end of the study period. During each treatment session, the children and parents were asked to report the number of completely dry nights and possible adverse effects since the previous treatment.

KHT points that are responsible for kidney, bladder, and cerebral function were stimulated with the E-beam machine for 20 seconds. The patients were grouped into 2 categories: group 1 children started the study with the functional cords; group 2 started the study with the fake cords. Data were expressed as percentage of number of dry nights per time period of observation and separated into baseline period (pretreatment), study period 1 (during treatment with the 1st cord), and study period 2 (during treatment with the 2nd cord). The statistical analysis was done with the Wilcoxon signed-rank test. 

Each patient was contacted 3 months after completing the study and asked to report the average number of dry nights attained during the previous 3 weeks. Patients who remained dry for a minimum of 90% of the nights were considered cured.

Editor's Note: Glossary of hand points: Hand Back Shu points for Kidney (I-19) and Bladder (I-22), hand Mu points for Kidney (J-23) and Bladder (A-3), Shu/Yuan/Source point for Kidney (J-3), Bladder Jing/Source point (I-37), and the hand Du-Mo extraordinary meridian (H-2/I-38).

RESULTS
Completing the study were 26 children (78%): 14 males (53%) and 12 females (47%). Ages ranged from 5-13 years with a mean of 6.5 years. A positive family history of enuresis was elicited in 69%; 6 children (23%) had been unsuccessfully treated with intranasal desmopressin. Eleven children were randomized to group 1, and 15 children to group 2.
The characteristics of each child completing the study and individual patient outcomes are shown in Table 1. Both groups significantly improved between baseline and the end of the 1st study period. Of those in group 1, 10/11 (91%) reported an improvement (P = .002). Of those in group 2, 12/15 (80%) reported an improvement over baseline (P<.001). The degree of improvement between baseline and period 1 was higher in group 1 (median improvement of 24 vs 10 percentage points in group 2, P = .07).

Both groups tended to improve during the 2nd period as well. Group 1 experienced an improvement in 6/11 (55%), while group 2 reported improvement in 10/15 (67%). The improvement in group 2 was statistically significant (P = .02). The difference in the median degree of improvement between the 2 groups during period 2 was not statistically significant (4 vs 10 percentage points; P = .42). Of all children, 53% were considered cured 3 months after completing the study. There were no reports of adverse effects to hand therapy.

DISCUSSION
The 53% cure rate reported 3 months after the conclusion of this study falls within the range of clinical responses considered favorable for traditional treatments.1-6,11-14 There were no adverse effects attributed to KHT. These results suggest that KHT is a reasonable treatment option for primary nocturnal enuresis in children. Several studies on the effect of acupuncture on enuresis are also encouraging, some of them reporting outcomes measured as percentage of completely dry nights ranging from 40% to 86%.15-17,21,22 However, these results need to be interpreted with caution. Without the benefit of a randomized and placebo-controlled design, clinical outcomes resulting from acupuncture treatments are difficult to interpret objectively, and are likely to generate acupuncture performance biases due to the elusive influence of the subjective experience factor shared by the patient and acupuncturist.23-25 Furthermore, when studying conditions such as enuresis that are multifactorial in nature and have high rates of spontaneous resolution and response to placebo, blind randomization into treatment and control groups appears essential.1-3,9,12,23-25

It is feasible that subjective elements involved in the patient-physician interaction play a particularly crucial role in treatment outcomes of primary nocturnal enuresis. The drama attached to the alarm system's loud noise when it senses urine in the bed sheets may partly explain why this option is reported to be the most effective treatment for nocturnal enuresis.3,5,6,9,13 A similar subjective effect could be attributed to the beneficial therapeutic impact of acupuncture which this study supports. The use of the E-beam machine permitted a randomized, double-blind, placebo-controlled design, with each child serving as his or her own control. The improvement noted in both groups, regardless of the functional status of the E-beam machine cords, affirms the beneficial influence of the subjective factors introduced by KHT. However, above and beyond this, actual hand therapy did have a distinctly favorable effect: group 1 (treatment with real cords between baseline and period 1) had a higher improvement rate, and group 2 improved significantly during the 2nd period (upon switching from fake to real cords).

The selection of points in this study was intended to improve kidney, bladder, and cerebral function. Whether alternative point selection, longer duration of treatment, or a larger sample of patients would have changed the results substantially is unknown.

CONCLUSION  
This study suggests that KHT offers a safe and reasonable treatment option for childhood primary nocturnal enuresis. The beneficial effect appears to be the result of both subjective factors introduced by the hand therapy experience, and a direct effect from the electromagnetic stimulation of hand points. The E-beam machine used in the manner described in this study may be a valuable tool to conduct double-blind, placebo-controlled clinical research in medical acupuncture.  

ACKNOWLEDGEMENT
I am indebted to Dr Larry Magder for his help with the statistical analysis.

REFERENCES

1. Kaneko K, Fujinaga S, Ohtomo Y, Shimizu T, Yamashiro Y. Combined pharmacotherapy for nocturnal enuresis. Pediatr Nephrol. 2001;16:662-664.
2. Gill D. Enuresis through the ages. Pediatr Nephrol. 1995;9:120-122.
3. Alon US. Nocturnal enuresis. Pediatr Nephrol. 1995;9:94-103.
4. Stenberg A, Lackgren G. Desmopressin tablets in the treatment of severe nocturnal enuresis in adolescents. Pediatrics. 1994;94:841-846.
5. Rappaport L. The treatment of nocturnal enuresis: where are we now? Pediatrics. 1993;92:465-466.
6. Scharf MB, Pravda MF, Jennings SW, Kauffman R, Ringel J. Childhood enuresis: a comprehensive treatment program. Psychiatr Clin North Am. 1987; 10:655-666.
7. Longstaffe S, Moffatt ME, Whalen JC. Behavioral and self-concept changes after six months of enuresis treatment: a randomized, controlled trial. Pediatrics. 2000;105:935-940.
8. von Gontard A, Mauer-Mucke K, Pluck J, Berner W, Lehmkuhl G. Clinical behavioral problems in day- and night-wetting children. Pediatr Nephrol. 1999;13:662-667.
9. Bartolozzi G, Boldrini A, Salmeri A, Vitali E. Evaluation and treatment of the enuretic child: eight years' experience [in Italian]. Pediatr Med Chir. 1991;13:389-393.
10. Rittig S, Knudsen UB, Norgaard JP, Pedersen EB, Djurhuus JC. Abnormal diurnal rhythm of plasma vasopressin and urinary output in patients with enuresis. Am J Physiol. 1989;256:F664-F671.
11. Burke JR, Mizusawa Y, Chan A, Webb KL. A comparison of amitriptyline, vasopressin and amitriptyline with vasopressin in nocturnal enuresis. Pediatr Nephrol. 1995;9:438-440.
12. Koff SA. Cure of nocturnal enuresis: why isn't desmopressin very effective? Pediatr Nephrol. 1996;10:667-670.
13. Bartolozzi G, Savino B, Calzolari C, et al. Treatment of nocturnal enuresis with a sound alarm [in Italian]. Pediatr Med Chir. 1985;7:115-120.
14. Miller K, Goldberg S, Atkin B. Nocturnal enuresis: experience with long-term use of intranasally administered desmopressin. J Pediatr. 1989;114: 723-726.
15. Serel TA, Perk H, Koyuncuoglu HR, Kosar A, Celik K, Deniz N. Acupuncture therapy in the management of persistent primary nocturnal enuresis: preliminary results. Scand J Urol Nephrol. 2001;35:40-43.
16. Caione P, Nappo S, Capozza N, Minni B, Ferro F. Primary enuresis in children: which treatment today? Minerva Pediatr. 1994;46:437-443.
17. Capozza N, Creti G, De Gennaro M, Minni B, Caione P. The treatment of nocturnal enuresis: a comparative study between desmopressin and acupuncture used alone or in combination [in Italian]. Minerva Pediatr. 1991;43:577-582.
18. Tae-Woo Yoo. Koryo Hand Acupuncture. Eckman P, ed. Korea: Eum Yang Mek Jin Publishing Co; 1977.
19. Jodorkovsky R. Hand acupuncture experience in pediatric patients. Medical Acupuncture. 1999;11(1):25-28.
20. Jodorkovsky R. Hand acupuncture treatment for chronic asthma in children. Medical Acupuncture. 2000/2001;12(2):52.
21. Jodorkovsky R. Pediatric acupuncture and Koryo Hand Acupuncture. In: Handbook of Faculty Syllabus Materials. 13th Symposium of the American Academy of Medical Acupuncture; March 22-25, 2001; New Orleans, La.
22. Scott J, Barlow T. Acupuncture in the Treatment of Children. 3rd ed. Eastland Press; 1991.
23. Rotchford J. Acubriefs Newsletter. Vol 2 Issue 10.
24. Stux G, Birch S. Proposed standards of acupuncture treatments for clinical studies. In: Stux G, Hammerschlag R, eds. Clinical Acupuncture: Scientific Basis.
25. Lao L, Ezzo, Berman BM, Hammerschlag R. Assessing clinical efficacy of acupuncture: considerations for designing future acupuncture trials. In: Clinical Acupuncture: Scientific Basis. New York, NY: Springer-Verlag; 2000.

AUTHOR INFORMATION
Dr Roberto Jodorkovsky is in private practice specializing in Pediatrics and Medical Acupuncture, and is Clinical Associate Professor of Pediatrics at the University of Maryland School of Medicine.

Roberto Jodorkovsky, MD, DABMA, FAAMA*
7658 Belair Rd
Baltimore, MD 21236
Phone: 410-882-6841 • Fax: 410-882-8478 • E-mail: rjodorkovsky@hcmt.com

*Send all correspondence and reprint requests to Dr Jodorkovsky at the above address.

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