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Article |

Omeprazole:  Therapy of Choice in Intellectually Disabled Children FREE

Clarisse J. M. Böhmer, PhD, MD; Riet C. Niezen-de Boer, MD; Elly C. Klinkenberg-Knol, PhD, MD; Stephan G. M. Meuwissen, PhD, MD
[+] Author Affiliations

From the Department of Internal Medicine, Medisch Centrum Alkmaar, Alkmaar (Dr Böhmer), Bartiméus, Center for Visually Handicapped–Visually and Intellectually Handicapped, Zeist (Dr Niezen-de Boer), and the Department of Gastroenterology, Academic Hospital, Vrije Universiteit, Amsterdam (Drs Klinkenberg-Knol and Meuwissen), the Netherlands.


Arch Pediatr Adolesc Med. 1998;152(11):1113-1118. doi:10.1001/archpedi.152.11.1113.
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Objective  To study extensively the therapeutic approach of gastroesophageal reflux disease in intellectually disabled children.

Design  We studied the effect of omeprazole sodium on healing and symptom relief in 52 institutionalized intellectually disabled children (male-female, 21:31; mean age, 15.4 years; range, 4-19 years).

Intervention  Endoscopically proven esophagitis (grades I-IV, Savary-Miller classification) was treated with omeprazole sodium, 40 mg/d (20 mg/d for children weighing <20 kg) as healing dose for 3 months, and 20 mg/d (10 mg/d for children weighing <20 kg) as maintenance dose for another 3 months. After 3 and 6 months, results of treatment were evaluated using symptom scoring and/or endoscopy. For patients with relapse, the dose was increased.

Results  At first endoscopy, 19 patients (36%) of 52 showed grade I esophagitis; 20 (38%), grade II; 6 (12%), grade III; and 7 (13%), grade IV. In 44 (86%) of 51 patients, treatment was effective in healing esophagitis and keeping patients in remission, independent of the severity of esophagitis. In 7 patients (14%), a symptomatic relapse was observed after decreasing the dose. However, these patients became symptom free again after increasing the dose and showed healing on endoscopy at the end of the study. One child did not finish the study for reasons not related to therapy. Marked improvement of persistent vomiting, regurgitation, food refusal, iron deficiency anemia, and signs of depression was seen at the end.

Conclusions  Omeprazole is highly effective for all grades of esophagitis in intellectually disabled children, without adverse effects. The dose needed to maintain the remission can be titrated according to the reflux symptoms. One disadvantage of medical therapy is that it is open ended, in contrast to operation, but surgery in this population has high mortality and complication rates.

Figures in this Article

GASTROESOPHAGEAL reflux disease (GERD), defined using results of a pathological 24-hour pH test, and reflux-esophagitis have been documented in a high percentage of intellectually disabled children.1,2 Characteristic reflux symptoms of GERD in this population are persistent vomiting, hematemesis, depressive symptoms, and rumination. Regurgitation, iron deficiency anemia, food refusal, and recurrent pneumonia also are seen more often in children with GERD.1,3 Complications of GERD are seen more frequently, including severe esophagitis,1,3 peptic strictures,4 Barrett syndrome,5 iron deficiency anemia, blood in the stools or frank gastrointestinal tract bleeding,6 and aspiration pneumonia.7 However, endoscopy is believed by many physicians to be too stressful for these patients, and therefore is performed in a few cases only. Hence, the diagnosis often will be delayed until complications occur. Another reason for diagnosing GERD in a late stage may be the indistinct or nonspecific symptom presentation.811

The therapeutic approach of GERD in intellectually disabled children has not been studied extensively. For more than 2 decades, antireflux surgery was accepted as appropriate treatment for severe GERD in children when pharmacological treatment failed, despite the high rates of failure, complications, and morbidity.815 In adults with endoscopically proven esophagitis, omeprazole sodium has been shown to be far superior to standard histamine receptor antagonists in terms of symptom relief, healing of esophagitis, and prevention of relapse.1618 The potential usefulness of omeprazole also has been studied in small groups of children with severe GERD, again with high efficacy.1921 Long-term omeprazole therapy also was shown to be safe.22 In our study, we evaluated the efficacy of omeprazole sodium, 40 mg/d as healing dose (in children weighing <20 kg, 20 mg/d was given), and 20 mg/d as maintenance dose (in children weighing <20 kg, 10 mg/d was given) in intellectually disabled children with grades I to IV esophagitis. In addition, reflux symptoms were scored before and after treatment to evaluate the efficacy of therapy.

From October 1, 1995, until October 31, 1997, in 13 institutions in the Netherlands and Belgium, 69 intellectually disabled children with IQs of less than 50 underwent endoscopy because of symptoms including vomiting, regurgitation, food refusal, hematemesis, and behavioral problems. Fifty-two children (male-female ratio, 21:31; mean age, 15.4 years [range, 4-19 years] median weight, 27.8 kg [range, 16-70 kg]) were found to have esophagitis and were included in the study (Table 1). The 13 centers from which the patients were selected were situated throughout both countries, and distribution of IQ, sex, age, and predisposing factors was equal according to the Dutch Registry for Intellectually Disabled.

Table Graphic Jump LocationPatient Characteristics and Treatment Dose

The inclusion criteria were age younger than 20 years, an IQ of less than 50, endoscopically verified grades I to IV reflux esophagitis,23 and written informed consent from the custodians (legal representatives). Some patients already used the following antireflux medication: ranitidine, 300 mg (n=12); and cisapride (n=9). Five patients underwent previous Nissen fundoplication.

SYMPTOM SCORE

At visits 1, 2, and 3, the following symptoms were scored to evaluate the effect of therapy: persistent vomiting, hematemesis, rumination, regurgitation, depressive symptoms, iron deficiency anemia, food refusal, recurrent pneumonia, restlessness, and screaming episodes. Symptoms were defined as present if they appeared at least 4 times a month. The median length of symptoms was 7.4 years (range, 7 months to 16 years).

STUDY DESIGN
Visit 1

At baseline, all patients with endoscopically verified esophagitis of grades I to -IV23 received the healing dose of omeprazole for 3 months (Figure 1).

Place holder to copy figure label and caption
Figure 1.

Treatment regimen with omeprazole sodium in intellectually disabled individuals. GE indicates gastroenterologist.

Graphic Jump Location
Visit 2

At 3 months, clinical evaluation (in all patients) and control endoscopy if symptoms had not improved (in 5 patients [10%]) were performed. (This strategy was chosen as the contributing institutes considered this additional endoscopy too stressful for the patients.) If the reflux symptoms had vanished, omeprazole therapy was decreased to maintenance dose. If symptoms persisted and endoscopy revealed that the esophagitis was improved but not healed, the healing dose was continued. When the degree of esophagitis was unchanged, the dose was increased to 60 mg/d (40 mg/d for children weighing <20 kg).

Visit 3

After 6 months, all patients underwent endoscopy. If the esophagitis was healed, the maintenance dose of omeprazole was continued. In case endoscopy revealed a relapse, the dose of omeprazole was increased to the healing dose.

Visit 4

Control endoscopy was performed after 9 months of therapy (only in patients with a relapse at visit 3). When the esophagitis was healed, the healing dose of omeprazole was continued. Treatment success was defined as endoscopically verified healing (grade 0 esophagitis).

ENDOSCOPY

Patients in whom GERD was suspected underwent endoscopy in 8 different hospitals in the Netherlands and Belgium. Findings were taped on video or photographed. Endoscopic results were listed on a registration form, including severity of reflux esophagitis following the Savary-Miller classification,23 and presence of a hiatal hernia, Barrett esophagus (with length measured in centimeters following biopsy), and strictures.

ETHICAL APPROVAL AND INFORMED CONSENT

Permission was asked from all committees and persons involved. First, the Subcommittee for the Ethics of Human Research of the Academic Hospital, Vrije Universiteit, Amsterdam, the Netherlands, gave consent for this study. Second, the Medical Ethical Committee of the institutes for intellectually disabled individuals gave their approval. Third, all custodians (legal representatives of the incapacitated individuals) gave their informed consent for participation of their pupil and for the anonymous use of medical information for scientific research.

STATISTICAL ANALYSES

The following tests were used for statistical evaluation: χ2 test, Fisher exact probability test, unpaired Student t test, Yates corrected test, and McNemar test. P <.05 was considered significant.

EVALUATION OF SYMPTOMS

Reflux symptoms at the start and after 6 months of treatment were evaluated by the same physician of each institute using quantitative scales. Persistent vomiting (P=.001), regurgitation (P=.002), iron deficiency anemia (P=.01), recurrent pneumonia (P=.02), screaming episodes (P=.05), restlessness (P=.04), and depressive symptoms (P=.01) were markedly improved after healing of the esophagitis (Figure 2).

Place holder to copy figure label and caption
Figure 2.

Reflux symptoms before and after omeprazole sodium therapy. Asterisk indicates significantly different (P<.05).

Graphic Jump Location
RELATIONSHIP BETWEEN SYMPTOMS AND SEVERITY OF THE ESOPHAGITIS

No relationship between different symptoms and the severity of esophagitis was demonstrated. Furthermore, the patients with grade IV esophagitis were significantly older compared with the patients with grades I to III esophagitis (P=.009).

RELATIONSHIP AMONG SEVERITY OF THE ESOPHAGITIS, DOSE REQUIRED, AND RELAPSE RATE AFTER FUNDOPLICATION

We found no differences among the severity of esophagitis, the dose required, or the relapse rate in children with or without past fundoplication. The median age was 16.1 years, which was comparable to that of the overall studied population.

ENDOSCOPIC FINDINGS AND RESPONSE TO TREATMENT

Results of diagnostic endoscopy showed 19 patients (36%) of 52 with grade I esophagitis; 20 (38%), grade II; 6 (12%), grade III; and 7 (13%), grade IV. In 40 patients (77%), esophagitis was accompanied by hiatal hernia. In 7 patients (13%), a Barrett esophagus was diagnosed using results of biopsy, accompanied in 3 (6%) by peptic strictures. After endoscopy, 49 patients started healing omeprazole sodium therapy at 40 mg/d and 3 at 20 mg/d.

After 3 months of therapy, 47 (90%) of 52 patients were asymptomatic, including the 3 patients who received the smaller maintenance dose. Five patients had no clear improvement of their symptoms and underwent endoscopy; 3 of these showed endoscopic improvement, but grade I or II esophagitis was still present. The healing dose of omeprazole was continued in these patients. The remaining 2 patients had no esophagitis.

All patients underwent endoscopy after 6 months of treatment. Seven (14%) of 51 patients had persistent symptoms, and became symptom free after 3 additional months of omeprazole healing therapy. All of them had esophagitis at endoscopy (2 patients had grade I; 4 patients, grade II; and 1 patient, grade III). Therefore the dose was increased in 6 patients to 40 mg/d and in 1 patient who received 10 mg/d, to 20 mg/d. In the remaining 44 patients in remission, omeprazole sodium therapy, 20 mg/d, was continued. One child did not finish the study, because endoscopy was not allowed due to pulmonary problems. The 3 children who were still treated with omeprazole sodium, 40 mg/d, were healed after 6 months.

The 7 patients with endoscopic abnormalities at 6 months underwent endoscopy after 9 months, and all were healed. The dose of omeprazole sodium in 6 patients remained 40 mg/d, and in 1 patient because of his weight, 20 mg/d.

In summary, during the 9-month study, in 48 (94%) of 51 patients, the healing and maintenance doses of omeprazole sodium were effective. Six patients (12%) suffered relapse when the maintenance dose was started, but they healed effectively with the increased dose. One patient (2%) suffered relapse when the dose of omeprazole sodium was reduced to 10 mg/d, but healed effectively with the 20-mg/d dose. Relapses were not related to the different grades of esophagitis before entry to the study.

SIDE EFFECTS OF OMEPRAZOLE

No disabling side effects during omeprazole therapy were seen. One child did not finish the study for reasons not related to therapy. Omeprazole is shown to be safe and effective in intellectually disabled children.

Our longitudinal study has shown that, independent of the severity of esophagitis, all studied institutionalized intellectually disabled children experienced complete healing with omeprazole. Moreover, with a maintenance dose, children maintained their remission during a maximal follow-up of 9 months.

Failure of drug treatment occurred frequently before the availability of proton pump inhibitor therapy for reflux esophagitis in intellectually disabled children. During the past 20 years, the therapy of choice was antireflux surgery in this population, despite a high complication rate. Mortality due to surgery varied from 8.8% to 9.4%,8,9,11,13 and postoperative complications, from 12% to 50%.12,14,15,18 Despite the high number of complications and the need for reoperation in 15% of these patients, surgery has still been advocated in recent literature as the therapy of choice for GERD in this population. In adults with endoscopically proven esophagitis, omeprazole has been shown to be far superior to standard histamine receptor antagonists in terms of symptom relief, healing of the esophagitis, and prevention of relapse.1618 In children, omeprazole was only tested and shown to be effective and safe for the treatment of severe GERD.1922 In a retrospective study among institutionalized intellectually disabled individuals, symptom scores after at least 1 year of therapy demonstrated low healing rates after surgery, antacids, or histamine receptor antagonist therapy, while only omeprazole has shown to be effective, even in complicated esophagitis.3 In a large, prospective study among intellectually disabled adults, omeprazole was effective in all patients for all grades of esophagitis.24 In our study, omeprazole was also shown to be effective for all grades of esophagitis in intellectually disabled children. The 40-mg dose instead of the normal 20-mg dose was chosen, because this population often suffers from severe and complicated esophagitis. After the initial treatment with 40 mg/d, 20 mg/d was found to be an adequate dose for maintenance. After treatment with omeprazole, all studied children were healed, and no disabling side effects occurred. Notwithstanding, 1 disadvantage of medical therapy is that it is open ended, in contrast to operation. However, surgery in this population has high mortality and complication rates compared with no disabling side effects of omeprazole. Furthermore, lifelong therapy in this population is much more limited than in the intellectually healthy population.

It was a remarkable observation that nearly 25% of the studied intellectually disabled children suffered from severe or complicated esophagitis. The diagnosis in this patient group frequently will be delayed until complications occur, due to nonspecific symptoms and the reluctance to submit these patients to endoscopy. This is confirmed by the fact that children with grade IV esophagitis were significantly older compared with those with grades I to III esophagitis. Symptoms associated with GERD1 were scored before and after treatment, and marked improvement occurred. However, rumination did not show any improvement; an explanation may be that rumination is a deliberate phenomenon.

A prospective prevalence study1 concluded that all institutionalized intellectually disabled adults with certain risk factors for reflux esophagitis (ie, scoliosis, cerebral palsy, use of anticonvulsant drugs or other benzodiazepines, IQ of less than 35, persistent vomiting, hematemesis, rumination, and depressive symptoms) should undergo pH testing wherever possible. Consequently, individuals with positive results of a pH test should undergo endoscopy. However, in combination with our results, we have to consider the possibility of blind treatment with omeprazole of intellectually disabled children with the indicated risk factors, which were equal in adults and children. Objective symptom scoring before and after therapy is certainly needed and valuable to evaluate the effect of therapy.

Our study shows that in intellectually disabled children, omeprazole is highly effective in all grades of esophagitis; adverse effects did not occur. The GERD had to be diagnosed using endoscopy, but the dose could be titrated based on clinical symptoms. We believe follow-up endoscopy is only necessary in children with persistent symptoms. We strongly recommend that omeprazole therapy be started following our schedule and continued on a long-term basis to prevent relapses and to avoid complications such as Barrett esophagus and esophageal cancer. The quality of life in this population improves markedly without invasive and often complicated surgery.

Accepted for publication June 16, 1998.

Supported by ASTRA Pharmaceutical Holland, Zoeteneer.

This study was made possible through the help and cooperation of the medical staffs from the following institutes for the intellectually disabled: Bartiméushage (Doorn), de Brink (Vries), Reigersdaal (Heerhugo-Waard), Kadijkerkoog (Purmerend), 't Rijtven (Duerne), Hooge Burch (Zwammerdam), de Blauwe Kamer (Breda), Amstel Meer (Aalsmeer), de Hartekamp (Heemstede), de Kloek (Nunspeet), Dr Dubbelman (Kundelstaart), the Netherlands; and Gilsbos (Gierle) and Michielsheem (Brussels), Belgium. We are greatly indebted for the support of the following gastroenterologists: in the Netherlands, M. J. A. Alleman, MD, Rijnland Hospital, Alphen aan de Rijn; Adriaan C. Douwes, PhD, Academic Hospital, Vrije Universiteit, Amsterdam; G. N. Groen, MD, St Jansdal, Harderwijk; Jan R. Vermeijden, MD, Spaarne Hospital, Haarlem; and Jos H. S. M. Nadorp, PhD, St Antonius Hospital, Nieuwegein; in Belgium, Mirjam J. H. M. van Winckel, PhD, University Hospital, Gent; K. van der Steen, PhD; H Hartkliniek, Asse; and R. Harlet, PhD; St Jozef Hospital, Turnhout. Jan A. J. M. Taminiau, PhD, MD, provided professional advice about pediatric issues.

Editor's Note: It's nice to know that relief for at least 1 problem faced by these children might just be a swallow away.—Catherine D. DeAngelis, MD

Corresponding author: S. G. M. Meuwissen, PhD, MD, Department of Gastroenterology, University Hospital, Vrije Universiteit, PO Box 7057, 1007 MB Amsterdam, the Netherlands (e-mail: sgm.meuwissen@azvu.nl).

Böhmer  CJMNiezen-de Boer  MCKlinkenberg-Knol  ECNadorp  JHSMMeuwissen  SGM The prevalence of gastroesophageal reflux (GER) and refluxesophagitis (RE) in severely mentally handicapped [abstract]. Gastroenterology. 1996;110A66
Deganello  ATamassia  GGaburro  D Peptic disease in paediatric patients: a diagnostic and therapeutic contribution. Drugs Exp Clin Res. 1990;1675- 83
Böhmer  CJMNiezen-de Boer  MCKlinkenberg-Knol  ECNadorp  JHSMMeuwissen  SGM Gastroesophageal reflux disease in institutionalised intellectually disabled individuals. Neth J Med. 1997;51134- 139
Link to Article
Byrne  WJEuler  ARAshcraft  ENash  DGSeibert  JJGolladay  ES Gastroesophageal reflux in the severely retarded who vomit: criteria for and results of surgical intervention in 22 patients. Surgery. 1982;9195- 98
Sondheimer  JMMorris  BA Gastroesophageal reflux among severely retarded children. J Pediatr. 1979;94710- 714
Link to Article
Orchard  JLStramat  JWolfgang  MTrimpey  A Upper gastrointestinal tract bleeding in institutionalized mentally retarded adults: primary role of esophagitis. Arch Fam Med. 1995;430- 33
Link to Article
Staiano  ADel Giudice  ERomano  AFlorimonte  LSimcone  D Neuroimaging correlates of severe gastrointestinal clinical manifestations in children with neurologic disorders [abstract]. Gastroenterology. 1996;110A842
Leape  LLRamenofsky  ML Surgical treatment of gastroesophageal reflux in children. AJDC. 1980;134935- 938
Albanese  CTToulbin  RBUllman  ILewis  JSmith  SD Percutaneous gastrojejunostomy versus Nissen fundoplication for enteral feeding of the neurologically impaired child with gastroesophageal reflux. J Pediatr. 1993;123371- 375
Link to Article
Borgstein  ESHeij  HABeugelaar  IDEkkelkamp  SVos  A Risks and benefits of antireflux operations in neurologically impaired children. Eur J Pediatr. 1994;153248- 251
Link to Article
Chang  JHColn  CDStrickland  ADAndersen  JM Surgical management of gastroesophageal reflux in severely mentally retarded children. J Ment Defic Res. 1987;311- 7
Wilkinson  JDDudgeon  DLSondheimer  JM A comparison of medical and surgical treatment of gastroesophageal reflux in severely mentally retarded children. J Pediatr. 1981;9202- 205
DeCou  JMShanter  NAKarl  SR Feeding Roux-en-Y jejeunostomy in the management of severely neurologically impaired children. J Pediatr Surg. 1993;281276- 1280
Link to Article
Spitz  L Surgical treatment of gastroesophageal reflux in severely retarded children. J R Soc Med. 1982;75525- 529
Turnage  RHOldham  KTConan  AGBlanne  CE Late results of fundoplication for gastroesophageal reflux in infants and children. Surgery. 1989;105457- 464
Klinkenberg-Knol  ECJansen  JMBJFesten  HPM Double-blind multicentre comparison of omeprazole and ranitidine in the treatment of reflux oesophagitis. Lancet. 1987;1349- 351
Link to Article
Dent  JYeomans  NDMackinnon  M Omeprazole v ranitidine for prevention of relapse in reflux oesophagitis. Gut. 1994;35590- 598
Link to Article
Hallerbäck  BUnge  PCarling  L Omeprazole or ranitidine in long-term treatment of reflux oesophagitis. Gastroenterology. 1994;1071305- 1311
Gunasekaran  TSHassall  E Efficacy and safety of omeprazole for severe gastroesophageal reflux in children. J Pediatr. 1993;123148- 154
Link to Article
Martin  PBImong  SMKrischer  JNoblett  HRSandhu  BK The use of omeprazole for resistant oesophagitis in children. Eur J Pediatr Surg. 1996;6195- 197
Link to Article
Hassall  EIsrael  DMShepherd  R  et al.  Omeprazole for chronic erosive esophagitis in children: a multicenter study of dose requirements for healing [abstract]. Endoscopy. 1997;29 ((7)) E15Abstract 33.13
Hassall  E Wrap session: is the Nissen slipping? can medical treatment replace surgery for severe gastroesophageal reflux disease in children? Am J Gastroenterol. 1995;90121- 126
Savary  MMiller  G The Oesophagus Handbook and Atlas of Endoscopy.  Solothurn, Switzerland Verlag Glassmann AG1978;
Böhmer  CJMNiezen-de Boer  MCKlinkenberg-Knol  EC  et al.  Gastro-esophageal reflux disease in intellectually disabled individuals: leads for diagnosis and the effect of omeprazole therapy. Am J Gastroenterol. 1997;921475- 1479

Figures

Place holder to copy figure label and caption
Figure 1.

Treatment regimen with omeprazole sodium in intellectually disabled individuals. GE indicates gastroenterologist.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Reflux symptoms before and after omeprazole sodium therapy. Asterisk indicates significantly different (P<.05).

Graphic Jump Location

Tables

Table Graphic Jump LocationPatient Characteristics and Treatment Dose

References

Böhmer  CJMNiezen-de Boer  MCKlinkenberg-Knol  ECNadorp  JHSMMeuwissen  SGM The prevalence of gastroesophageal reflux (GER) and refluxesophagitis (RE) in severely mentally handicapped [abstract]. Gastroenterology. 1996;110A66
Deganello  ATamassia  GGaburro  D Peptic disease in paediatric patients: a diagnostic and therapeutic contribution. Drugs Exp Clin Res. 1990;1675- 83
Böhmer  CJMNiezen-de Boer  MCKlinkenberg-Knol  ECNadorp  JHSMMeuwissen  SGM Gastroesophageal reflux disease in institutionalised intellectually disabled individuals. Neth J Med. 1997;51134- 139
Link to Article
Byrne  WJEuler  ARAshcraft  ENash  DGSeibert  JJGolladay  ES Gastroesophageal reflux in the severely retarded who vomit: criteria for and results of surgical intervention in 22 patients. Surgery. 1982;9195- 98
Sondheimer  JMMorris  BA Gastroesophageal reflux among severely retarded children. J Pediatr. 1979;94710- 714
Link to Article
Orchard  JLStramat  JWolfgang  MTrimpey  A Upper gastrointestinal tract bleeding in institutionalized mentally retarded adults: primary role of esophagitis. Arch Fam Med. 1995;430- 33
Link to Article
Staiano  ADel Giudice  ERomano  AFlorimonte  LSimcone  D Neuroimaging correlates of severe gastrointestinal clinical manifestations in children with neurologic disorders [abstract]. Gastroenterology. 1996;110A842
Leape  LLRamenofsky  ML Surgical treatment of gastroesophageal reflux in children. AJDC. 1980;134935- 938
Albanese  CTToulbin  RBUllman  ILewis  JSmith  SD Percutaneous gastrojejunostomy versus Nissen fundoplication for enteral feeding of the neurologically impaired child with gastroesophageal reflux. J Pediatr. 1993;123371- 375
Link to Article
Borgstein  ESHeij  HABeugelaar  IDEkkelkamp  SVos  A Risks and benefits of antireflux operations in neurologically impaired children. Eur J Pediatr. 1994;153248- 251
Link to Article
Chang  JHColn  CDStrickland  ADAndersen  JM Surgical management of gastroesophageal reflux in severely mentally retarded children. J Ment Defic Res. 1987;311- 7
Wilkinson  JDDudgeon  DLSondheimer  JM A comparison of medical and surgical treatment of gastroesophageal reflux in severely mentally retarded children. J Pediatr. 1981;9202- 205
DeCou  JMShanter  NAKarl  SR Feeding Roux-en-Y jejeunostomy in the management of severely neurologically impaired children. J Pediatr Surg. 1993;281276- 1280
Link to Article
Spitz  L Surgical treatment of gastroesophageal reflux in severely retarded children. J R Soc Med. 1982;75525- 529
Turnage  RHOldham  KTConan  AGBlanne  CE Late results of fundoplication for gastroesophageal reflux in infants and children. Surgery. 1989;105457- 464
Klinkenberg-Knol  ECJansen  JMBJFesten  HPM Double-blind multicentre comparison of omeprazole and ranitidine in the treatment of reflux oesophagitis. Lancet. 1987;1349- 351
Link to Article
Dent  JYeomans  NDMackinnon  M Omeprazole v ranitidine for prevention of relapse in reflux oesophagitis. Gut. 1994;35590- 598
Link to Article
Hallerbäck  BUnge  PCarling  L Omeprazole or ranitidine in long-term treatment of reflux oesophagitis. Gastroenterology. 1994;1071305- 1311
Gunasekaran  TSHassall  E Efficacy and safety of omeprazole for severe gastroesophageal reflux in children. J Pediatr. 1993;123148- 154
Link to Article
Martin  PBImong  SMKrischer  JNoblett  HRSandhu  BK The use of omeprazole for resistant oesophagitis in children. Eur J Pediatr Surg. 1996;6195- 197
Link to Article
Hassall  EIsrael  DMShepherd  R  et al.  Omeprazole for chronic erosive esophagitis in children: a multicenter study of dose requirements for healing [abstract]. Endoscopy. 1997;29 ((7)) E15Abstract 33.13
Hassall  E Wrap session: is the Nissen slipping? can medical treatment replace surgery for severe gastroesophageal reflux disease in children? Am J Gastroenterol. 1995;90121- 126
Savary  MMiller  G The Oesophagus Handbook and Atlas of Endoscopy.  Solothurn, Switzerland Verlag Glassmann AG1978;
Böhmer  CJMNiezen-de Boer  MCKlinkenberg-Knol  EC  et al.  Gastro-esophageal reflux disease in intellectually disabled individuals: leads for diagnosis and the effect of omeprazole therapy. Am J Gastroenterol. 1997;921475- 1479

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Omeprazole: therapy of choice in intellectually disabled children. Arch Pediatr Adolesc Med 1998;152(11):1113-8.