Saudi Journal of Gastroenterology

ORIGINAL ARTICLE
Year
: 2010  |  Volume : 16  |  Issue : 3  |  Page : 154--160

Functional bowel disorders in Iranian population using Rome III criteria


Majid Sorouri, Mohammad A Pourhoseingholi, Mohsen Vahedi, Azadeh Safaee, Bijan Moghimi-Dehkordi, Asma Pourhoseingholi, Manijeh Habibi, Mohammad R Zali 
 Research Center for Gastroenterology and Liver Diseases, Shahid Beheshti University (M.C), Tehran, Iran

Correspondence Address:
Mohammad A Pourhoseingholi
Research Center for Gastroenterology and Liver Diseases, Shahid Beheshti University (M.C), Tehran
Iran

Abstract

Background/Aim: To study the prevalence and risk factors of functional bowel disorders (FBD) in Iranian community using Rome III criteria. Materials and Methods: This study was a cross-sectional household survey conducted from May 2006 to December 2007 in Tehran province, Iran, including 18,180 participants who were selected randomly and interviewed face-to-face by a validated questionnaire based on Rome III criteria. Results: In all, 1.1% met the Rome III criteria for irritable bowel syndrome (IBS), 2.4% for functional constipation (FC), and 10.9% of the participants had any type of FBD. Among participants with functional dyspepsia, 83.8% had FBD; the majority cases were unspecified functional bowel disorder (U-FBD). Of the subjects fulfilling the IBS criteria, IBS with constipation (52%) was the most frequent subtype. In the multivariate analysis, women had a higher risk of any FBDs than men, except for functional diarrhea (FD). The prevalence of FBD, FC and FD increased and IBS decreased with increasing age. Marital status was only associated with a decrease in the risk of FBD and FD, respectively. IBS subtypes compared with FC and FD. There was no significant difference between FC and IBS with constipation (IBS-C), except for self-reported constipation; while, IBS with diarrhea (IBS-D) had more symptoms than FD. Conclusion: This study revealed a low rate of FBDs among the urban population of Tehran province. The ROME III criteria itself, and the problems with interpretation of the data collection tool may have contributed in underestimating the prevalence of FBD. In addition the reliability of recall over 6 months in Rome III criteria is questionable for our population.



How to cite this article:
Sorouri M, Pourhoseingholi MA, Vahedi M, Safaee A, Moghimi-Dehkordi B, Pourhoseingholi A, Habibi M, Zali MR. Functional bowel disorders in Iranian population using Rome III criteria.Saudi J Gastroenterol 2010;16:154-160


How to cite this URL:
Sorouri M, Pourhoseingholi MA, Vahedi M, Safaee A, Moghimi-Dehkordi B, Pourhoseingholi A, Habibi M, Zali MR. Functional bowel disorders in Iranian population using Rome III criteria. Saudi J Gastroenterol [serial online] 2010 [cited 2019 Aug 22 ];16:154-160
Available from: http://www.saudijgastro.com/text.asp?2010/16/3/154/65183


Full Text

Functional bowel disorders (FBDs) include the irritable bowel syndrome (IBS), functional bloating (FB), functional constipation (FC), functional diarrhea (FD), and unspecified FBD (U-FBD) attributed to the small bowel, colon, and rectum. Although symptoms (e.g. diarrhea, constipation, bloating, pain) may overlap across these disorders, IBS is more specifically defined as pain associated with change in bowel habit, and this is distinct from FD and constipation characterized by change in bowel habit and no pain, or functional bloating when there is no change in bowel habit. [1],[2] According to the ROME III criteria (the latest symptom-based diagnostic criteria of functional gastrointestinal disorders), onset of symptoms should begin at least 6 months before clinical presentation and the diagnostic criteria must be fulfilled for the last 3 months. [1],[2] This time frame is less restrictive than Rome II (12 weeks of symptoms over 12 months).

The estimated prevalence of FBD and its subtypes varies enormously depending on the diagnostic criteria employed. Considering Rome II criteria, FBD has prevalence between 12.1 and 41.6% in different populations, and it is more frequent in women than in men. [3],[4] In Iran, the prevalence of FBD was 40.1% in patients referred to a gastroenterology clinic. [5]

Of all FBDs, IBS has received more attention and its prevalence is 3-25%. [6],[7],[8] There are similar frequencies for IBS in Western countries, but may be lower in Asian countries and in African-American populations; however, there is a wide variation, even within individual countries. [1],[7],[8],[9] In Iran, the prevalence of IBS was reported to be 5.8% in the general population and 3-18.4% in some groups. [10],[5],[11],[12] While in the Rome II criteria, IBS was divided into three subtypes, in the Rome III criteria, it has four subtypes based on stool consistency alone: IBS with constipation (IBS-C), IBS with diarrhea (IBS-D), mixed IBS (IBS-M), and unsubtyped IBS (IBS-U). [2] It seems that IBS with an alternating stool pattern (IBS-A) (based on Rome II) maybe the most frequent IBS in Western countries, but in Asian countries there is no homogeneity. [11],[13,[14],[15],[16]

After IBS, FC seems to be the other more studied FBD. FC is a FBD that presents as persistently difficult, infrequent, or seemingly incomplete defecation, which does not meet IBS criteria. Constipation occurs in up to 27% of people depending on demographic factors, sampling, and definition. It affects all age groups and is most common in women and non-whites. [2],[6]

In Iran, the prevalence of FC is obscure in the general population but in some groups, it was 3.1-28%. [5],[12]

As for the other types of FBD, less data are available. Functional bloating (FB) is a recurrent sensation of abdominal distention that may or may not be associated with measurable distention, but is not part of another functional bowel or gastroduodenal disorder. [2] Up to 96% of IBS patients report this symptom and 10-30% of individuals in the general population report bloating during the previous year. [2]

The prevalence of FB was reported from 5.8% to 17.7%, [3],[4],[17] while the prevalence of FD was estimated from 0.4% to 9.6%. [3],[18],[19]

This paper aims to provide preliminary data on relative distribution of different types of FBD and their socio-demographic patterns based on a large sample of the general population, in Iran.

 Materials and Methods



This study was part of a cross-sectional household survey conducted from May 2006 to December 2007 in Tehran province, Iran, which aimed to find the prevalence of gastrointestinal symptoms [20],[21] and functional disorders [22],[23],[24] in Iranian community. A total of 18,180 adult persons drawn up randomly on the basis of the list of postal codes and random samples of these postal codes and their corresponding related address were drawn from the databank registry of Tehran central post office (approximately 5000 households selected and all members surveyed). These samples covered five cities including Tehran metropolitan, Damavand, Varamin, Firoozkouh, Pakdasht, and their rural constituencies. The sampled population was interviewed by trained health care workers at their own residence area. The research protocol was approved by the Ethics Committee of Research Center for Gastroenterology and Liver Diseases, Shaheed Beheshti Medical University, and all persons who participated in the study signed a consent form.

The questionnaire included two parts, with the first part containing data regarding personal and family characteristics (such as age, sex, educational level), which were recorded from every participant in the first place. In addition, participants were informed and asked about 11 gastrointestinal (GI) symptoms including abdominal pain/discomfort, constipation, diarrhea, bloating, heartburn/acid regurgitation, proctalgia, nausea/vomiting, fecal incontinence, bloody or black stool (melena), anorexia/weight loss, and difficulty of swallowing.

Participants who reported any of the above symptoms were referred for participating in the second interview by physicians in the vicinity. The second part of questionnaire consisted of questions about different gastrointestinal disorders, characterized on the basis of Rome III criteria. [4],[5] The section of Rome III criteria was standardized in Persian designed by a working group, translated from English to Persian.

The validity and reliability of the Persian questionnaire was tested in a pilot study on 400 participants from city of Damavand. For validity study, the language, content, concurrence, and construct validities were examined. The test-retest reliability was good and the Cronbach alpha coefficient values were above 0.7 for all major symptoms included in the tool. Minor corrections, however, were made regarding some symptoms. [22],[23],[24]

Some demographic and clinical variables including sex (male/female), age, marital status (single, married, widow), education, and body mass index (BMI), were included in the analysis. The response rate for the first and second interviews was more than 92%, respectively.

All statistical analysis carried out using SAS version 9.1 (SAS Institute Inc., Cary, NC, USA). Pearson's chi-square, contingency tables and logistic regression were performed to test for independence between discrete variables. Continuous variables are presented as mean±standard deviation and other parameters as frequency and percentage. A P value of 0.05 or less was considered statistically significant and all reported P values were two sided.

 Results



A total of 18,180 entered in this cross-sectional study. The response rate was more than 92% and those who refused to participate in the interview were replaced with additional random samples. Among these participants 9072 (49.9%) were women. The mean age of men and women was 38.9±17.4 and 38.4±16.7 years (PP [3],[4] it was more frequent among women, and this was also true with all subtypes of FBD except FD. Our results confirms the study of Thompson et al. in Canada which showed higher prevalence of FBD in female [3] and other studies, including an Iranian population based, demonstrating higher prevalence of IBS and FC among women. [4],[5],[6],[7],[8],[25],[26],[27],[28],[29],[30],[31] Nevertheless, some studies in Taiwan, India, and another Iranian study (among university students) reported the same prevalence of IBS among men and women. [11],[32],[33],[34],[35]

History of abdominal surgery was significant only in the models of FC and U-FBD. Similarly, having reviewed relative evidence on IBS only, a systematic review by Hasler and Schoenfeld states that there is still poor evidence to link IBS and a history of abdominal surgery. [36] But Roshandel et al. reported a high prevalence of abdominal surgery among FBD patients referred to gastroenterology clinics. [5]

This large population-based survey demonstrates a community prevalence of IBS of 1.1% (0.6% of men and 1.5% of women). Although the Rome criteria are simplified in the 3rd version, our estimate of the prevalence of IBS is one of the lowest that has been reported. In Turkey, the overall prevalence of IBS was 6.3% while a similar rate of 4.1% was found in a study conducted in Hong Kong among ethnic Chinese subjects. [37],[38] In Iran, the prevalence of IBS was reported to be 5.8% in the general population and 3-18.4% in some groups. [5],[10],[11],[12] Our finding indicated low prevalence for IBS. As one possibility, the prevalence estimates may vary because of the specific questions used to elicit the information. Careful interpretation of the abdominal discomfort or pain and stool characteristics is the most important step in recognizing IBS. In this study, face-to-face interview was adopted and all subjects were requested to fill in a questionnaire assisted by trained health personnel who could provide the relatively precise interpretation of the items in the questionnaire. Another problem is in the recall nature of the data in asking the Rome III criteria questions we used. It is surely difficult for anyone to remember precisely whether they had abdominal pain over the past 6 months, unless their symptom frequency lies near either extreme of these ranges.

Our finding of a somewhat lower age for IBS patients is compatible with previous studies, [28],[30],[33] although two studies in China and England found no relationship between IBS and age. [16],[39]

Of the subjects fulfilling the IBS diagnostic criteria in our study, the majority of cases were IBS-C (45.3%), while the cases with IBS-D (13.4%) were the least common. Together IBS-M and IBS-U comprised of 39.5% cases. An international survey of 40,000 subjects across eight industrialized European countries by Hungin et al. also revealed IBS-A (63%) to be the most frequent subtype, followed by IBS-D (21%) and IBS-C (16%). [13] Another survey in the USA by the same author and using the same methodology showed that IBS-A comprised the majority (66%) of IBS cases, followed by IBS-D (21.3%) and IBS-C (12.7%). [14] In contrast, a Spanish study on 2000 subjects showed that IBS-C (37%) was the most common subtype among 63 subjects meeting Rome II, followed by IBS-D (25%) and IBS-A (23%). [40] In Asia, a study in Malaysia also showed that IBS-C was the most frequent subtype (77.4%), and IBS-A and IBS-D comprised 15.5 and 7.1% of IBS patients, respectively. [15] In contrast to our study, Xiong et al. reported IBS-D to be the most frequent (74.1%) and IBS-A as the least frequent (10.8%) subtype in China. [16] In Iran, among IBS patients referred to gastroenterology clinic, Roshandel et al. reported IBS-A as the most frequent (60%) and IBS-C and IBS-D to be 29.1% and 10.9%, respectively. Interestingly, another Iranian study on 1200 university students from western Iran reported IBS-C (50%) as the most frequent and IBS-A (21%) as the least frequent subtype (with IBS-D comprising 29% of IBS cases). [11] It seems that IBS-A maybe the most frequent IBS in Western countries, but in Asian countries there is no homogeneity.

Advancing age and female gender were independently associated with a diagnosis of FC in our study. Talley et al. did not find gender to be associated with FC; [41] this differs from most other studies, which have found FC rates to be higher in women. [42],[43],[44] Like ours, Sandler et al.'s study in the United States found no association between FC and education. [43] The association of FC with advancing age concurs with other studies. [28],[42],[43],[45],[46],[47]

To date, it seems that most studies have focused on IBS and FC, and other FBDs as defined by Rome criteria have been investigated less. In two studies in Israel and one study in Canada, the prevalence of FB was reported to be 5.8-17.7%; [3],[4],[17] but in our study, the prevalence of FB was as low as 1.5%. Our results confirm the study of Thompson et al. in Canada which showed higher prevalence of FB in females. [3]

In all participants, 8.8% of individuals reported bloating during the previous 6 months, but it was 10-30% based on Rome II in some community surveys. [48],[49]

In our study, FD had a low prevalence. It was reported by 9.6% of Minnesota residents [18] and 4.8% and 8.5% of people throughout the United States and Canada, respectively. [3],[19] On the other hand, an Israeli study on 981 individuals showed that 0.4% had FD. [4] In Iran, the prevalence of FD was reported to be 2% in 1023 gastroenterology outpatients. [5]

In U-FBD patients, bloating was the most frequent symptom (64.4%) and 46.7% of them reported abdominal pain. Interestingly, functional dyspepsia (based on Rome III criteria) coexisted in 92% of U-FBD. In Rome criteria, coexistence of the symptom of bloating and any functional GI disorder excludes FB and patient will be categorized as U-FBD. Therefore, it seems that a majority of U-FBD patients may have been those who did not fulfill IBS or FB criteria.

To our knowledge, because patients were sampled from a general population, the selection biases that might apply to a specialist or hospital derived sample could not arise. Although all of participants live in Tehran province and our data may not represent the entire Iranian population, the large sample size serves as a strength of the study.

In conclusion, this study revealed a low rate of FBDs among the urban population of Tehran province. Our experience indicated that the ROME III criteria itself, and the problems with interpretation of the data collection tool might have taken part in underestimating the prevalence of FBD. In addition the reliability of recall over 6 months in ROME III is questionable for our population.

 Acknowledgements



The authors acknowledge the contributions of time and effort from the persons who involved in obtaining interview information in this study. They also extend thanks to Dr. Farhad Hosseinpanah and Mrs. Shiva for manuscript preparation. This research work was totally funded by the Research Center for Gastroenterology and Liver Diseases affiliated to Shahid Beheshti University (MC), Tehran, Iran.

References

1Drossman DA. The functional gastrointestinal disorders and the Rome III process. Gastroenterology 2006;130:1377-90.
2Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. Gastroenterology 2006;130:1480-91.
3Thompson WG, Irvine EJ, Pare P, Ferrazzi S, Rance L. Functional gastrointestinal disorders in Canada: First population-based survey using Rome II criteria with suggestions for improving the questionnaire. Dig Dis Sci 2002;47:225-35.
4Sperber AD, Shvartzman P, Friger M, Fich A. Unexpectedly low prevalence rates of IBS among adult Israeli Jews. Neurogastroenterol Motil 2005;17:207-11.
5Roshandel D, Rezailashkajani M, Shafaee S, Zali MR. Symptom patterns and relative distribution of functional bowel disorders in 1,023 gastroenterology patients in Iran. Int J Colorectal Dis 2006;21:814-25.
6Chang L. Review article: epidemiology and quality of life in functional gastrointestinal disorders. Aliment Pharmacol Ther 2004;20:31-9.
7Delvaux M. Functional bowel disorders and irritable bowel syndrome in Europe. Aliment Pharmacol Ther 2003;18:75-9.
8Kang JY. Systematic review: the influence of geography and ethnicity in irritable bowel syndrome. Aliment Pharmacol Ther 2005;21:663-76.
9Chang FY, Lu CL. Irritable bowel syndrome in the 21st century: Perspectives from Asia or South-east Asia. J Gastroenterol Hepatol 2007;22:4-12.
10Hoseini-Asl MK, Amra B. Prevalence of irritable bowel syndrome in Shahrekord, Iran. Indian J Gastroenterol 2003;22:215-6.
11Ghannadi K, Emami R, Bashashati M, Tarrahi MJ, Attarian S. Irritable bowel syndrome: an epidemiological study from the west of Iran. Indian J Gastroenterol 2005;24:225-6.
12Massarrat S, Saberi-Firoozi M, Soleimani A, Himmelmann GW, Hitzges M, Keshavarz H. Peptic ulcer disease, irritable bowel syndrome and constipation in two populations in Iran. Eur J Gastroenterol Hepatol 1995;7:427-33.
13Hungin AP, Whorwell PJ, Tack J, Mearin F. The prevalence, patterns and impact of irritable bowel syndrome: an international survey of 40,000 subjects. Aliment Pharmacol Ther 2003;17:643-50.
14Hungin AP, Chang L, Locke GR, Dennis EH, Barghout V. Irritable bowel syndrome in the United States: prevalence, symptom patterns and impact. Aliment Pharmacol Ther 2005;21:1365-75.
15Tan YM, Goh KL, Muhidayah R, Ooi CL, Salem O. Prevalence of irritable bowel syndrome in young adult Malaysians: A survey among medical students. J Gastroenterol Hepatol 2003;18:1412-6.
16Xiong LS, Chen MH, Chen HX, Xu AG, Wang WA, Hu PJ. A population-based epidemiologic study of irritable bowel syndrome in South China: Stratified randomized study by cluster sampling. Aliment Pharmacol Ther 2004;19:1217-24.
17Sperber AD, Friger M, Shvartzman P, Abu-Rabia M, Abu-Rabia R, Abu-Rashid M, et al. Rates of functional bowel disorders among Israeli Bedouins in rural areas compared with those who moved to permanent towns. Clin Gastroenterol Hepatol 2005;3:342-8.
18Talley NJ, Zinsmeister AR, Van Dyke C, Melton LJ 3rd. Epidemiology of colonic symptoms and the irritable bowel syndrome. Gastroenterology 1991;101:927-34.
19Everhart JE, Go VL, Johannes RS, Fitzsimmons SC, Roth HP, White LR. A longitudinal survey of self-reported bowel habits in the United States. Dig Dis Sci 1989;34:1153-62.
20Zarghi A, Pourhoseingholi MA, Habibi M, Nejad MR, Ramezankhani A, Zali MR. Prevalence of gastrointestinal symptoms in the population of Tehran, Iran. Trop Med Int Health 2007;12:181-2.
21Zarghi A, Pourhoseingholi MA, Habibi M, Haghdost AA,, Solhpour A, Moazezi M, et al. Prevalence of gastrointestinal symptoms and the influence of demographic factors. Am J Gastroenterol 2007;102:441.
22Solhpour A, Pourhoseingholi MA, Soltani F, Zarghi A, Habibi M, Ghafarnejad F, et al. Gastro-esophageal reflux symptoms and body mass index: no relation among the Iranian population. Indian J Gastroenterol 2008;27:153-5.
23Barzkar M, Pourhoseingholi MA, Habibi M, Moghimi-Dehkordi B, Safaee A, Pourhoseingholi A, et al. Uninvestigated dyspepsia and its related factors in an Iranian community. Saudi Med J 2009;30:397-402.
24Pourhoseingholi MA, Kaboli SA, Pourhoseingholi A, Moghimi-Dehkordi B, Safaee A, Mansoori BK, et al. Obesity and functional constipation: A community-based study in Iran. J Gastrointest Liver Dis 2009;18:151-5.
25Bommelaer G, Poynard T, Le Pen C, Gaudin AF, Maurel F, Priol G, et al. Prevalence of irritable bowel syndrome (IBS) and variability of diagnostic criteria. Gastroenterol Clin Biol 2004;28:554-61.
26Lau EM, Chan FK, Ziea ET, Chan CS, Wu JC, Sung JJ. Epidemiology of irritable bowel syndrome in Chinese. Dig Dis Sci 2002;47:2621-4.
27Celebi S, Acik Y, Deveci SE, Bahcecioglu IH, Ayar A, Demir A, Durukan P. Epidemiological features of irritable bowel syndrome in a Turkish urban society. J Gastroenterol Hepatol 2004;19:738-43.
28Wei X, Chen M, Wang J. The epidemiology of irritable bowel syndrome and functional constipation of Guangzhou residents. Zhonghua Nei Ke Za Zhi 2001;40:517-20.
29Karaman N, Tόrkay C, Yφnem O. Irritable bowel syndrome prevalence in city center of Sivas. Turk J Gastroenterol 2003;14:128-31.
30Si JM, Chen SJ, Sun LM. An epidemiological and quality of life study of irritable bowel syndrome in Zhejiang province. Zhonghua Nei Ke Za Zhi 2003;42:34-7.
31Pare P, Ferrazzi S, Thompson WG, Irvine EJ, Rance L. An epidemiological survey of constipation in Canada: definitions, rates, demographics, and predictors of health care seeking. Am J Gastroenterol 2001;96:3130-7.
32Lu CL, Chen CY, Lang HC, Luo JC, Wang SS, Chang FY, Lee SD. Current patterns of irritable bowel syndrome in Taiwan: the Rome II questionnaire on a Chinese population. Aliment Pharmacol Ther 2003;18:1159-69.
33Gwee KA, Wee S, Wong ML, Png DJ. The prevalence, symptom characteristics, and impact of irritable bowel syndrome in an Asian urban community. Am J Gastroenterol 2004;99:924-31.
34Shah SS, Bhatia SJ, Mistry FP. Epidemiology of dyspepsia in the general population in Mumbai. Indian J Gastroenterol 2001;20:103-6.
35Ho KY, Kang JY, Seow A. Prevalence of gastrointestinal symptoms in a multiracial Asian population, with particular reference to reflux-type symptoms. Am J Gastroenterol 1998;93:1816-22.
36Hasler WL, Schoenfeld P. Systematic review: abdominal and pelvic surgery in patients with irritable bowel syndrome. Aliment Pharmacol Ther 2003;17:997-1005.
37Celebi S, Acik Y, Deveci SE, Bahcecioglu IH, Ayar A, Demir A, et al. Epidemiological features of irritable bowel syndrome in a Turkish urban society. J Gastroenterol Hepatol 2004;19:738-43.
38Kwan AC, Hu WH, Chan YK, Yeung YW, Lai TS, Yuen H. Prevalence of irritable bowel syndrome in Hong Kong. J Gastroenterol Hepatol 2002;17:1180-6.
39Heaton KW, O'Donnell LJ, Braddon FE, Mountford RA, Hughes AO, Cripps PJ. Symptoms of irritable bowel syndrome in a British urban community: consulters and nonconsulters. Gastroenterology 1992;102:1962-7.
40Mearin F, Balboa A, Badνa X, Barσ E, Caldwell E, Cucala M, Irritable bowel syndrome subtypes according to bowel habit: revisiting the alternating subtype. Eur J Gastroenterol Hepatol 2003;15:165-72.
41Talley NJ, Weaver AL, Zinsmeister AR, Melton LJ 3rd. Functional constipation and outlet delay: A population-based study. Gastroenterology 1993;105:781-90.
42Campbell AJ, Busby WJ, Horwath CC. Factors associated with constipation in a community based sample of people aged 70 years and over. J Epidemiol Community Health 1993;47:23-6.
43Sandler RS, Jordan MC, Shelton BJ. Demographic and dietary determinants of constipation in the US population. Am J Public Health 1990;80:185-9.
44Pare P, Ferrazzi S, Thompson WG, Irvine EJ, Rance L. An epidemiological survey of constipation in Canada: definitions, rates, demographics, and predictors of health care seeking. Am J Gastroenterol 2001;96:3130-7.
45Talley NJ, O'Keefe EA, Zinsmeister AR, Melton LJ 3rd. Prevalence of gastrointestinal symptoms in the elderly: A population-based study. Gastroenterology 1992;102:895-901.
46Talley NJ, Fleming KC, Evans JM, O'Keefe EA, Weaver AL, Zinsmeister AR, Melton LJ 3rd. Constipation in an elderly community: A study of prevalence and potential risk factors. Am J Gastroenterol 1996;91:19-25.
47Johanson JF, Sonnenberg A. The prevalence of hemorrhoids and chronic constipation. An epidemiologic study. Gastroenterology 1990;98:380-6.
48Sandler RS, Stewart WF, Liberman JN, Ricci JA, Zorich NL. Abdominal pain, bloating, and diarrhea in the United States: prevalence and impact. Dig Dis Sci 2000;45:1166-71.
49Talley NJ, Boyce P, Jones M. Identification of distinct upper and lower gastrointestinal symptom groupings in an urban population. Gut 1998;42:690-5.