The Prevalence of Gastroesophageal Reflux Disease in ... - Nature

THE AMERICAN JOURNAL OF GASTROENTEROLOGY © 1999 by Am. Coll. of Gastroenterology Published by Elsevier Science Inc.

Vol. 94, No. 3, 1999 ISSN 0002-9270/99/$20.00 PII S0002-9270(98)00735-7

The Prevalence of Gastroesophageal Reflux Disease in Institutionalized Intellectually Disabled Individuals C. J. M. Bo¨hmer, Ph.D., M. C. Niezen-de Boer, M.D., E. C. Klinkenberg-Knol, Ph.D., W. L. J. M. Deville´, M.D., J. H. S. M. Nadorp, Ph.D., and S. G. M. Meuwissen, Ph.D. Academic Hospital Vrije Universiteit, Department of Gastroenterology, Amsterdam; Bartime´us, Institute for Intellectually Disabled, Zeist; Academic Hospital Vrije Universiteit, Department of Epidemiology and Biostatistics, Amsterdam; and Antonius Hospital, Department of Gastroenterology, Nieuwegein, The Netherlands

OBJECTIVE: The prevalence of gastroesophageal reflux disease (GERD) was randomly investigated among Dutch and Belgian intellectually disabled individuals. METHODS: In six institutes including 1607 residents, 435 persons with IQ ,50 underwent 24-h esophageal pH-metry and were scored for possible predisposing factors and characteristic reflux symptoms. In 49 (11.2%) cases the test failed because of technical reasons. A pathological pH test was defined as a pH ,4 for .4.5% of the measured time. Subjects with a pathological pH test (patients) were compared with those with a normal pH test (controls). RESULTS: Of the remaining individuals, 51.8% (200/386) showed a normal pH test, whereas 186 showed a pathological pH test (median duration pH ,4: 14.2%, range: 4.5– 78.4%). As possible predisposing factors scoliosis, cerebral palsy, use of anticonvulsant drugs or other benzodiazepines, and IQ ,35 were found, whereas symptoms such as vomiting, hematemesis, rumination, and depressive symptoms were indicative for reflux. At endoscopy reflux esophagitis was diagnosed in 129 of the 186 patients (69.4%). In 61 (47.3%) of 129 patients, grade I, 43 (33.3%) grade II, 25 (19.4%) grade III/IV (Savary-Miller) were found. Barrett’s esophagus was found in 18 (14.0%) and peptic strictures in five (3.9%) cases. CONCLUSIONS: An abnormal 24-h pH-metry and symptoms suggestive for GERD were documented frequently in a large cohort of institutionalized intellectually disabled individuals. Further endoscopical evaluation confirmed the diagnosis of reflux esophagitis in the majority of these individuals. (Am J Gastroenterol 1999;94:804 – 810. © 1999 by Am. Coll. of Gastroenterology)

as based on classical symptoms such as heartburn (1, 2). At further clinical evaluation, in 2–10% of symptomatic individuals esophagitis will be diagnosed (3– 6). Previous studies have mentioned that 10 –25% of institutionalized intellectually disabled individuals have symptoms of vomiting (7–10), regurgitation (8 –13), or rumination (7, 8, 11, 14 –20). In the large majority of these individuals GERD has been suspected clinically (11); however, firm documentation of reflux esophagitis (RE) has usually not been obtained, because of lack of investigations. In a small series an abnormal endoscopy was found in 6.4 –9.5% (21) (M. van de Wiel, partly unpublished data, Dec. 1994). Probably this is an underestimation, because of the nonclassic symptom presentation (15, 22–24). In intellectually disabled individuals other symptoms, such as chronic obstructive pulmonary disease or respiratory complications, failure to thrive and a poor growth nutritional state may also be related to GERD (9, 25–29); severe grades of RE with peptic strictures and/or Barrett’s esophagus are frequently seen (3, 7, 8, 16) and upper gastrointestinal hemorrhage or aspiration pneumonia are regularly observed (7, 8, 14, 16, 30). In general, invasive procedures such as endoscopy are considered to be too stressful for intellectually disabled patients. The risk therefore exists that the diagnosis RE will be missed, with all clinical consequences for the patient. Therefore, the purpose of our study was to investigate the prevalence of GERD and RE in a randomly selected population of intellectually disabled individuals in The Netherlands and Belgium. Furthermore, we wanted to correlate possible factors predisposing for reflux as well as reflux symptoms with the results of 24-h pH-metry and endoscopy.

MATERIALS AND METHODS INTRODUCTION Gastroesophageal reflux disease (GERD) is the condition in patients who have symptoms or other problems arising from pathological acid reflux, often leading to esophagitis. In nearly 5% of the intellectually normal adult western population, gastroesophageal reflux disease (GERD) is suspected

This study was performed between October 1994 and March 1996 in four institutes in The Netherlands and two institutes in Belgium. Patient Selection Procedures The randomly selected population consisted of 510 of 1195 intellectually disabled individuals. In 9% (75) of the re-

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range 29 – 40 cm; NS). From these results we concluded the pH step-up method for our study to be sufficiently reliable. Before and after the measurement the catheter was standardized with solutions of pH 1.0 and 7.0. An ambulatory solid recorder was used with a sample frequency of 4 – 6/s (32). For analysis of the data we used an automated analysis computer program. A pathological pH test was defined as a pH ,4 for more than 4.5% of the measured time (34 –36). ENDOSCOPY. Patients with a pathological pH test underwent endoscopy within a few days after their pH measurement in seven different hospitals in The Netherlands and Belgium, to which centers patients were referred. Endoscopic findings were documented according to severity of RE following the Savary-Miller classification, presence of a hiatal hernia, Barrett’s esophagus with length measurement in centimeters, and presence of esophageal strictures (37). The presence of Helicobacter pylori and gastritis was histologically evaluated by biopsies from antrum and corpus.

Figure 1. Patient selection procedure for pH test and endoscopy.

quests, medical staff, nursing staff, educational services, or custodians did not give permission, usually because 24-h pH-metry was not considered to be useful for the patient or the investigational method was found to be too stressful. All individuals were tested using an IQ score following the International Classification of Diseases (ICD-10) of the World Health Organization (31). With this IQ score the level of intellectual disability has been classified in three groups: IQ 50 –70 is defined as mild disability, IQ 35–50 as moderate disability, and IQ ,35 as severe, and profound disability. Individuals with an IQ .50 were excluded, because they were supposed to be able to express their complaints. For 435 cases with an IQ ,50, written consent was obtained from their custodians. Furthermore, all were tested with a 24-h pH-metry (see Methods, below). Individuals with a pathological pH test were defined as patients and subjects with a normal pH test as controls. Some patients already received treatment for reflux; 28 patients used 300 mg ranitidine, seven patients cisapride, two patients prepulsid, and one patient 20 mg omeprazole. All medication was stopped $1 wk before the pH test. Methods (Fig. 1) TWENTY-FOUR-HOUR PH-METRY. We used monocrystalline antimony pH electrodes (32) in combination with an external reference electrode. The catheter was positioned 5 cm above the lower esophageal sphincter (LES) by the step-up method (33). Because the pH step-up method appears to be relatively inaccurate to locate the mid LES (32), we evaluated our methodology by comparing the step-up method with manometry (10 cases, median 33.0 cm; range 27–39 cm; NS) and endoscopy (200 cases, median 34.4 cm;

Definition of Possible Predisposing Factors, Reflux Symptoms, and Attributable Factors All 435 intellectually disabled individuals were scored for possible reflux symptoms, possible predisposing factors, possible attributable factors, and (if GERD was endoscopically diagnosed in the past) were defined as having previous endoscopic evidence of esophagitis. POSSIBLE PREDISPOSING FACTORS. These were defined as nonambulancy (29), scoliosis (11), cerebral palsy (8, 29), the use of anticonvulsive therapy including all benzodiazepines (38), and an IQ ,35 (severe intellectual disability). Nonambulancy was defined as at least semiambulancy and movement only with help (29). Cerebral palsy included neurological syndromes such as hemi-, tetra-, and quadriplegia, and overall hypotonia. POSSIBLE REFLUX SYMPTOMS. These were persistent vomiting (7, 9), hematemesis (29), rumination (17–20), regurgitation (12, 13), food refusal (23), recurrent pneumonia (19, 27, 28), and behavior problems such as automutilation, aggression, fear, episodes of screaming, depression, and restlessness (29). The symptoms were arbitrarily defined as being present when, after consultation with the attendant physician of the institute, they appeared at least four times/ month. Also, iron deficiency anemia, defined as at least twice/yr a hemoglobin decrease of 2 mmol/L, was scored as a reflux symptom. Rumination was defined as the deliberate regurgitation of food into the mouth, in part being ejected (emesis), while the rest was rechewed or swallowed (16 – 20). Regurgitation was defined as the condition in which the sudden effortless return of small volumes of gastric or esophageal contents into the pharynx and the mouth is present, which implies cricopharyngeal relaxation or insufficiency (8, 11–13).

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POSSIBLE ATTRIBUTABLE FACTORS. These were defined as age, body mass index (BMI), gender, Down’s syndrome, constipation (14), nasogastric tube feeding and gastrostomy feeding (PEG), and chronic obstructive pulmonary diseases (9, 27–29, 39). Ethical Approval and Informed Consent Dutch legislation differentiates between therapeutic and nontherapeutic medical research. Nontherapeutic research on children and intellectually disabled persons is not allowed. Therapeutic research is allowed in accordance with this law and the patient’s permission must be based on adequate information given by the medical practitioner (article 7:448, Wet Geneeskundige Behandel Overeenkomst/ Law Medical Treatment Agreement of the Netherlands). When investigation must be performed in intellectually disabled subjects, their custodians must be informed to give this permission. In case of poor compliance of intellectually disabled subjects, the procedure or therapy must be terminated. Permission to investigate was sought from the respective committees and individuals involved. First, the Subcommittee for the Ethics of Human Research of the University Hospital “Vrije Universiteit” in Amsterdam gave consent for this study, because the prevalence study was not possible to fulfill among any other population than the intellectually disabled population. The expected results were considered to be of major clinical importance for the overall population of intellectually disabled. Permission was granted with one major restriction: endoscopy was allowed only in those individuals with a pathological pH-metry result, because of the more stressful nature of an endoscopic examination, the need for transferral of the patient to the hospital, and the required sedation. Finally, the benefit of endoscopic evaluation in those individuals with a negative pH test was considered to be low. Second, approval of the Ethical Committee of the various institutes was obtained. Third, all guardians (legal representatives of the incapacitated individuals) were asked for written informed consent for participation of their subjects, and for the anonymous use of medical information for scientific research (article 7:450, Law Medical Treatment Agreement). Statistical Evaluation Results of evaluation in the respective institutes and countries were compared. Univariate associations between independent factors and disease status were tested by the Yates corrected x2 test or Fisher’s exact test when necessary. Differences in continuous variables were tested by the unpaired Student’s t test; univariate odds ratios with 95% confidence intervals were calculated. Forward and backward stepwise (to evaluate the most sensitive and specific model) logistic regression resulted in multivariate models for disease status, with standardized odds ratios for the variables remaining in the model. An a-level of 0.05 was used for statistical significance (40).

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Table 1. Differences Between Patients With Upright and Supine Reflux Patients

Patients

Patients

p

Upright Reflux Supine Reflux N 186 Time pH ,4 (%) 14.2 Range (%) 4.5–78.4 Duration: upright 10.8 (56) reflux, h (%) Duration: supine 8.4 (44) reflux, h (%)

111 13.9 4.5–69.2 10.0 (52)

75 14.4 4.9–78.4 10.8 (56)

NS NS NS NS

9.3 (48)

8.5 (44)

NS

RESULTS Prevalence of GERD The total population of six institutes included 1607 intellectually disabled persons. After IQ scoring, 412 persons (270 male, 142 female; mean age 37.6 yr, range 12– 82 yr) had an IQ .50 and were excluded from further evaluation. In 813 residents (479 men, 334 women; mean age 34.1 yr, range 4 –77) an IQ ,35 was found, whereas in 382 (225 male, 157 female; mean age 35.6 yr, range 7– 89 yr) the IQ was between 35 and 50. At random, 435 of 1607 (27%) individuals with an IQ ,50 underwent 24-hr pH-metry; this randomly selected population consisted of 48 (11%) children (,20 yr; 21 ,10 yr), which is comparable to the number of children among the overall institutionalized, intellectually disabled population. In 49 (11.2%) cases the test failed for technical reasons. Of the remaining individuals, 200 of 386 (51.8%) (mean age 35.1 yr, SD 17.7; 122 male, 78 female) showed a normal pH test, whereas 186 (mean 35.7 yr, SD 16.3; 108 male, 78 female) showed a pathological pH test (median duration pH ,4: 14.2%, range 4.5– 78.4%). The minimal measured time was 17 h, including a supine and upright period. There were no significant differences between patients with upright reflux compared with those with supine reflux (Table 1). In addition, there were no significant differences for age and gender between patients and controls. The age profile of the patients studied is comparable to the overall institutionalized population of intellectually disabled individuals. We found no differences in age between patients with or without GERD, and concluded that GERD in intellectually disabled individuals does not increase with age. Why this is different from the intellectually normal population, we don’t know. Possibly, this is due to the fact that risk factors, such as nonambulancy and medication, are already present at childhood, which is in contrast with the intellectually normal population. Those factors are more often found in the elderly. Possible Predisposing Factors and Possible Reflux Symptoms (Table 2) POSSIBLE PREDISPOSING FACTORS. The frequency of scoliosis, cerebral palsy, use of anticonvulsant drugs or other benzodiazepines, and IQ ,35 was significantly higher in patients than in controls.

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Table 2. Possible Predisposing Factors, Reflux Symptoms and Other Risk Factors Indicating GERD in a Randomly Selected Population of Intellectually Disabled Individuals

Patient status Predisposing Factors Nonambulancy Scoliosis Cerebral palsy Anticonvulsant drugs IQ ,35 Reflux symptoms Vomiting Hematemesis Iron deficiency anemia Rumination Regurgitation Food refusal Recurrent pneumonia Behavior problems Automutilation Aggression Fear Screaming Depression Restlessness Other risk factors Age, yr (mean) BMI (mean) Gender: male female Down’s syndrome Constipation Nasogastric tube PEG feeding

Abnormal pH Test (N 5 186)

Normal pH Test (N 5 200) OR 1.7 2.6 2.6 2.8 3.4

p

106 (57.0%) 93 (50.0%) 114 (61.3%) 134 (72.0%) 153 (82.3%)

93 (46.5%) 56 (28.0%) 69 (34.5%) 106 (53.0%) 137 (68.5%)

0.05 0.001 0.001 0.001 0.002

40 (21.5%) 26 (14.0%) 27 (14.5%)

25 (12.5%) 5 (2.5%) 23 (11.5%)

1.8 0.02 6.6 0.001 1.2 NS

57 (30.6%) 54 (29.0%) 53 (28.5%) 46 (24.7%) 89 (47.8%) 36 (19.4%) 36 (19.4%) 20 (10.8%) 45 (24.2%) 31 (16.7%) 36 (19.4%)

28 (20.0%) 42 (21.0%) 44 (22.0%) 37 (18.5%) 93 (46.5%) 39 (19.5%) 39 (19.5%) 14 (7.0%) 52 (26.0%) 16 (8.0%) 28 (14.0%)

2.5 1.5 1.2 1.3 0.6 0.8 0.8 1.9 1.0 3.6 2.4

0.001 0.06 NS NS NS NS NS NS NS 0.01 NS

34.7 (SD 15.3) 20.6 (SD 4.4) 108 (58.1%) 78 (41.9%) 21 (11.3%) 120 (64.5%) 12 (6.5%) 21 (11.3%)

35.1 (SD 16.7) 20.5 (SD 4.7) 122 (61.0%) 78 (39.0%) 19 (9.5%) 110 (55.0%) 11 (7.4%) 19 (9.5%)

1.4 1.5 1.4 0.9 1.2

NS NS NS NS NS 0.07 NS NS

Abbreviations: GERD 5 gastroesophageal reflux disease; BMI 5 body mass index; PEG 5 gastrostomy feeding; NS 5 not significant.

POSSIBLE REFLUX SYMPTOMS. Vomiting, hematemesis, rumination, and depression were found significantly more often in patients in comparison with controls. Previous endoscopic evidence of esophagitis, confirmed by endoscopy, was found in 52 (49%) patients compared with 10 (10%) controls (p , 0.001). Representativity of Randomly Selected Population This randomly selected population was compared with the total institutionalized, intellectually disabled population in The Netherlands (National Dutch Registration for the Care of Intellectually Disabled Individuals/Landelijke Registratie Zorg). Both groups were comparable. Only Down’s syndrome (p 5 0.01) and behavior difficulties (p 5 0.01) were more often seen in the overall institutionalized population. Prevalence of Esophagitis A total of 186 patients underwent endoscopy. In 30.6% of the investigations no esophagitis was detected. In all, 37.4% patients with esophagitis showed a hiatal hernia compared

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to 6.4% in all patients without esophagitis (p , 0.001). In 88.3% patients with esophagitis, gastritis or H. pylori infection was found compared to 87.9% in those patients without esophagitis (NS). No gastric or duodenal ulcers were diagnosed. In 61 (47.3%) of 129 patients grade I, 43 (33.3%) grade II, 25 (19.4%) grade III/IV (Savary-Miller) were found. Barrett’s esophagus was found in 18 (14.0%) and peptic strictures in five (3.9%) cases. Relation Between Results of pH Test and Endoscopy There was no significant relation between the pH test results and the endoscopic results. The median percentage of pH ,4 was not related to the severity of esophagitis. In patients with severe esophagitis there were no significant differences between pathological upright and pathological supine reflux (Fig. 2). Multivariable Analysis Forward and backward stepwise logistic regression analysis was performed for two models, one model for individuals with previous endoscopic evidence of esophagitis, and one for individuals without GERD in the past. PATIENTS WITH PREVIOUS ENDOSCOPIC EVIDENCE OF ESOPHAGITIS. The combination of an IQ ,35, scoliosis, the use of anticonvulsant drugs, hematemesis, and depression was overall predictive for an abnormal pH-metry in 72.6% of the cases, with a sensitivity of 72.2% and a specificity of 72.9%. The combination of cerebral palsy and rumination was overall predictive for an abnormal pH-metry in 68.4% of the cases, with a sensitivity of 63.0% and a specificity of 74.6%. PATIENTS WITHOUT PREVIOUS ENDOSCOPIC EVIDENCE OF ESOPHAGITIS. The combination of an IQ ,35 or cerebral palsy, scoliosis, the use of anticonvulsant drugs, hematemesis, rumination, and depression was predictive for an abnormal pH-metry in 68.4% of the cases, with a sensitivity of 77.8% and a specificity of 58.9%. Possible predisposing factors for reflux symptoms, however, could distinguish patients with an abnormal 24-h pHmetry and endoscopic abnormalities from those without esophagitis.

DISCUSSION The present study has shown that the prevalence of GERD in a large group of institutionalized intellectually disabled individuals with an IQ ,50 is considerable. It is very likely that, in the past, clinicians caring for this patient group frequently overlooked the existence of reflux esophagitis and only asked for further confirmation of the diagnosis GERD by means of invasive diagnostic tests when symptoms, such as vomiting, food refusal, or hematemesis occurred. Previous studies have suggested that a high prevalence of GERD was likely, usually based on symptomatology (7, 8, 11, 14 –16). From the literature it

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Figure 2. Relationship between results of pH test, including upright and supine episode, and endoscopy.

appears that .15% of the total intellectually disabled population appears to be at risk; in a recent Dutch study, GERD was suspected in 42 (7%) of 573 residents, thereafter confirmed in 38% by endoscopy (M. van de Wiel, unpublished data, Dec. 1994). In a recent study we analyzed, in the first instance, the prevalence of GERD in intellectually disabled individuals, who were selected by means of their clinical symptomatology (42) such as automutilation, food refusal, fear and restlessness, vomiting, regurgitation, and rumination. Rumination in intellectually disabled individuals differs from this condition in intellectually normal persons in that, in the intellectually disabled, it is in most cases a communication method (i.e., behavioral condition), and is present both day and night and not only after a meal (as in young children). Therefore, in intellectually disabled individuals, rumination causes much more damage because these individuals not only ruminate food (with a normal pH), but most of the time gastric fluid with a very low pH, inducing esophageal damage. Patients with an abnormal 24-h pH-metry were compared with those with a normal measurement, but of all listed symptoms only the use of anticonvulsant drugs and cerebral palsy were discriminative. Therefore one may conclude that it is impossible to suspect GERD on symptomatology only, and that confirmation by 24-h pH-metry and/or endoscopy is needed. Because to the best of our knowledge no studies exist, in which the prevalence of GERD has been studied prospectively in a randomly selected population, we approached several institutions in The Netherlands and Belgium. Permission to start the study was granted relatively quickly by the respective medical ethical committees. However, there was one drawback; control endoscopy was prohibited by medical-ethical arguments in incapacitated individuals with a normal 24-h pH-metry. pH Monitoring is generally accepted to be the “gold standard” for identification of reflux; however, it is well known that, even in studies

comparing the esophageal acid exposure in patients with endoscopically proven esophagitis, the sensitivity and specificity in segregating GERD-positive from GERD-negative populations is only 77–100% and 85–100%, respectively (43). Concluding that, by excluding subjects with normal pH testing, even more patients with erosive disease may have been overlooked and an even higher prevalence of GERD in this patient population may be present. In our study we evaluated the prevalence of GERD in a randomly selected population, although we considered the possibility of selection bias. Therefore, we compared our random population with the clinical features in the overall institutionalized intellectually disabled population and found no major differences except for prevalence of Down’s syndrome and behavioral difficulties. It could be possible that intellectually disabled individuals with Down’s syndrome or behavioral problems are more difficult to investigate because of a higher degree of noncooperation; therefore, more frequent failing of tests in this part of the intellectually disabled population could have interfered with the results. Thereafter, we evaluated the procedures of selection and the numbers of patients dropping out during this selection and concluded that 75% of the Dutch population was evaluated, whereas in Belgium 96% of the population was studied. Because of the fact that the prevalence of GERD was equal in both countries, the studied population was concluded to be at random. Complication rates of chronic RE in this population appear to be quite high: strictures (3, 7, 8, 16) and Barrett’s esophagus (16) were frequently found. In intellectually normal patients with esophagitis, Barrett’s esophagus occurs in 10 –20% (44 – 47). In contrast, in one study the presence of Barrett’s esophagus among the intellectually disabled was found in 26% of adult patients with esophagitis (16). Apparently, intellectual disability is a risk factor for Barrett’s esophagus (48). We demonstrated grade III/IV esophagitis

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in nearly 20% of the intellectually disabled patients, but the frequency of Barrett’s esophagus (14%) was comparable to that in the intellectually normal population. Also, a high prevalence of Helicobacter pylori infection was demonstrated; however, in only two of the endoscopied cases a duodenal ulcer was found without antisecretory medication, so possibly this population has a less dangerous type of Helicobacter pylori. The main cause of GERD is insufficiency of the LES with regard to influence on mean basal tone (e.g., by medication); also, in this population, an incompetence of the antireflux barrier play a role. The sphincter tone differs considerably during the day. Medication such as anticholinergics and sedatives, which are frequently prescribed for intellectually disabled patients, decrease this tone (49). Also, increased intra-abdominal pressure (i.e., because of adiposity or constipation) and abdominal compression (i.e., from scoliosis or cerebral palsy), which are regularly encountered in the intellectually disabled population, influence the LES pressure (8, 11, 29, 31, 50, 51). The presence of a hiatal hernia is not necessary for the development of GERD or esophagitis, but is found to be a major risk factor. The prevalence of hiatal hernia is increased in elderly patients (52, 53), in persons with spinal deformities (46), and in intellectually disabled children and adolescents (54). We could not affirm this high percentage. However, in this study cerebral palsy, use of anticonvulsant drugs, and scoliosis were indeed associated with GERD. The high prevalence of GERD among the intellectually disabled might be due partly to the difficulty in recognizing the clinical problem, because symptoms are often unclear and nonspecific (15, 22–24, 29). Symptoms of vomiting (7–9), regurgitation, or rumination (12, 17, 18) are found in 10 –25% of the intellectually disabled. In our study we found vomiting, hematemesis, and rumination as possible reflux symptoms. This is partly in contrast with the results of van Winckel, who demonstrated that persistent vomiting and wheezing were risk factors (29). This is possibly due to the fact that the population studied by van Winckel consisted only of neurologically impaired children with severe brain damage. The multivariate analysis was used to define a risk profile for GERD, with a high sensitivity and specificity rate. However, overall, nearly 50% of the intellectually disabled population has GERD, according to this study. In an intellectually normal population, if a percentage of 50% for a disease were found, everyone without question should be screened for the disease; but in practice we have observed that in an intellectually disabled population it is impossible to screen all individuals. Therefore we looked for a risk profile to limit the population to investigate later. In conclusion, GERD is a major clinical problem among intellectually disabled individuals that is obviously overlooked and underestimated. Our study has shown that the prevalence of GERD and reflux esophagitis in intellectually disabled individuals living in institutions, both in The Neth-


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erlands and in Belgium, GERD and reflux esophagitis is high, especially in those with specific and well defined risk factors.

ACKNOWLEDGMENTS This study was made possible through the help and cooperation of the medical staffs from the following six institutes: Mrs. I. Hofman and pastor H. P. Meiniger, Bartime´ushage, Doorn; Mrs. M. Kusse and Mrs. M. Rekers, Hartekamp, Heemstede; H. Gimbel and D.J. Vendrig, Reigersdaal, Heerhugowaard; R. Dekker and A. de Vries, Kloek, Nunspeet in The Netherlands and J. Meireleire, Gilsbos, Gierle; and Mrs. M. de Coen and R. Gorelbeke, Michielsheem, Dilbeek in Belgium. We are greatly indebted for the support of the following gastroenterologists: G. N. Groen, St. Jansdal, Harderwijk; HARE Tuynman, Medical Center Alkmaar, Alkmaar; J. R. Vermeijden, Spaarne Hospital, Haarlem; J. H. Voskuil, St. Antonius Hospital, Nieuwegein, The Netherlands, and K. van der Steen, H. Hartkliniek, Asse; R. Harlet, St. Jozef Hospital, Turnhout, Belgium. We acknowledge ASTRA Pharmaceuticals for financial support, and especially Mrs. D. M. Dols for consultative support. Also we would like to thank Synectics Medical, in particular B. vd Linden, for financial, technical, and statistical support for the pH-metric tests. Reprint requests and correspondence: Prof. S. G. M. Meuwissen, Ph.D., Department of Gastroenterology, Academic Hospital “Vrije Universiteit,” P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. Received Apr. 8, 1998; accepted Oct. 5, 1998.

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