American Journal of Epidemiology Copyright © 1992 by The Johns Hopkins University School of Hygiene and Public Health Al rights reserved
Vol. 136, No. 2 Printed in U.S.A.
Onset and Disappearance of Gastrointestinal Symptoms and Functional Gastrointestinal Disorders
Nicholas J. Talley,1* Amy L. Weaver,2 Alan R. Zinsmeister,2 and L. Joseph Melton I
Functional gastrointestinal disorders, including the irritable bowel syndrome, account for up to 40% of referrals to gastroenterologists, but accurate data on the natural history of these disorders in the general population are lacking. Using a reliable and valid questionnaire, the authors estimated the onset and disappearance of symptoms consistent with functional gastrointestinal disorders. An age- and sex-stratified random sample of 1,021 eligible residents of Olmsted County, Minnesota, aged 30-64 years were initially mailed the questionnaire; 82% responded (n = 835). In a remailing to responders 12-20 months later, 83% responded again (n = 690). The age- and sexadjusted prevalence rates per 100 for irritable bowel syndrome, chronic constipation, chronic diarrhea, and frequent dyspepsia were 18.1 (95% confidence interval (Cl) 15.121.1), 14.7 (95% Cl 11.9-17.4), 7.3 (95% Cl 5.3-9.3), and 14.1 (95% Cl 11.5-16.8), respectively, on the second mailing. Symptoms were not significantly associated with nonresponse to the second mailing; moreover, the estimated prevalence rates were not significantly different from the first mailing. Among the 582 subjects free of the irritable bowel syndrome on the first survey, 9% developed symptoms during 795 person-years of follow-up, while 38% of the 108 who initially had the irritable bowel syndrome did not meet the criteria after 146 person-years of follow-up. Similar onset and disappearance rates were observed for the other main symptom categories. While functional gastrointestinal symptoms are common in middle-aged persons and overall prevalence appears relatively stable over 12-20 months, substantial turnover is implied by the observed onset and disappearance rates; several potential sources of bias do not seem to account for this variation. Am J Epidemiol 1992;136:165-77. colonic diseases, functional; constipation; diarrhea; dyspepsia; gastroenterology; gastroesophageal reflux; prevalence; questionnaires
The functional gastrointestinal disorders represent a group of conditions characterized by chronic or recurrent gastrointestinal symptoms that cannot be explained by structural or biochemical abnormalities (1).
These disorders are important because they are highly prevalent in the general population and have a significant impact on health care, yet epidemiologic studies of these problems remain sparse (1, 2). Up to 40 percent of referrals to gastroenterologists are for functional gastrointestinal problems (1, 2). In 1985, it was estimated that there were 4.2 million office visits for functional bowel disorders in the United States; over 2.2 million medications were prescribed (3). Yet, this is probably a gross underestimate of the problem. In a population-based study, Talley et al. have reported that approximately one quarter of the middle-aged Caucasians sampled had symptoms consistent with func-
Received for publication June 25, 1991, and In final form January 24, 1992. Abbreviation: Q, confidence internal. ' Division of Gastroenterology and Internal Medicine, Mayo Clinic and Foundation, Rochester, MN. i Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, MN. Reprint requests to Dr. Nicholas J. Talley, Gastroenterology Unit, Mayo dine, Rochester, MN 55905. This work was supported by the Rochester Epidemiology Project (AR 30582) from the National Institutes of Health and by a research grant from Glaxo.
165
166
Talleyetal.
tional gastrointestinal disorders, although most did not seek care (4, 5), confirming the results of studies of volunteers and other nonpatient groups (6, 7). However, there remain substantial gaps in our knowledge. Thus, it is uncertain whether the prevalence of functional gastrointestinal symptoms is stable or not. How often functional gastrointestinal symptoms develop in persons in the general population previously free of complaints is also unknown, and it is unclear whether persons who do develop such symptoms in the community continue to have them for prolonged periods. The commonest of the functional gastrointestinal disorders is the irritable bowel syndrome, which is characterized by abdominal pain usually associated with a chronic but erratic disturbance of defecation (I, 2). There is evidence that the standard medical history, when carefully obtained, can strongly point to the irritable bowel syndrome rather than organic disease being the diagnosis. Manning et al. (8) first reported that six symptoms could discriminate the irritable bowel syndrome from organic gastrointestinal disease in outpatients; the presence of two or more of these symptoms had a sensitivity and specificity of 94 percent and 55 percent, respectively, for identifying the syndrome (8). The discriminant value of these symptoms has subsequently been confirmed; we determined that the Manning criteria score had a sensitivity of 70 percent and specificity of 90 percent for discriminating pain-predominant irritable bowel syndrome from health (9). Diagnostic criteria based on the consensus of a panel of clinical investigators have also been developed (referred to as the Rome criteria), although their clinical utility has not been established (1,2). We have previously reported on the development of a reliable and valid self-report questionnaire for the measurement of functional gastrointestinal symptoms (10, 11), and we have obtained population-based data on a well-characterized random sample of middle-aged persons residing in Olmsted County (4, 5). We aimed to restudy this sample of the Olmsted County population,
using a similar questionnaire, in order to determine the stability of the prevalence rates and to estimate the onset and disappearance of individual gastrointestinal symptoms and symptom categories (including abdominal pain, irritable bowel syndrome, chronic constipation, chronic diarrhea, and dyspepsia). MATERIALS AND METHODS Subjects
Approval was provided by the Institutional Review Board of the Mayo Clinic in April 1987 to contact inhabitants of Olmsted County, Minnesota. The Olmsted County population comprises approximately 100,000 persons of which 98 percent are white; sociodemographically, the community is similar to the United States white population. Mayo Clinic is the major provider of medical care for this population. It has been determined previously that about 15 percent of all Mayo Clinic registrations are from the local population and that, each year, over half of the County population is seen at one of the Clinic facilities. During any given 4-year period, over 95 percent of local residents will have had at least one medical contact with a local care provider. An important feature of the Rochester environment is that each of these providers uses a dossier (or unit record) system, whereby all medical information for each individual is accumulated in a single record. The pertinent clinical data are accessible because the Mayo Clinic has maintained, since 1910, extensive indices based on clinical and histologic diagnoses and surgical procedures. The system was further developed by the Rochester Epidemiology Project (12), which created similar indices for the records of the other providers of medical care to residents of Rochester and Olmsted County. The Rochester Epidemiology Project medical records linkage system therefore provides what is essentially an enumeration of the population from which samples can be drawn. Using this system, we randomly selected 1,120 persons living in Olmsted County as of 1988 who were aged 30-64
Gastrointestinal Symptoms
years and stratified by age (in 5-year intervals) and sex (equal numbers of men and women). The study population should have been, therefore, a representative sample of Olmsted County residents 30-64 years of age.
Survey
Initially, the medical records of candidate subjects were reviewed. Sixty-four subjects (6 percent) were excluded because they were non-Caucasians (n = 16); had been diagnosed as having a major psychotic episode or dementia (n = 15); had undergone major abdominal surgery comprising nephrectomy (n = 5), renal transplant (n = 2), or bowel resection (« = 9) in the past; or currently had a major organic medical disease including active cancer (n = 7), ulcerative colitis (n = 1), severe congestive heart failure or valvular heart disease (n = 4), severe coronary artery disease (n = 2), or miscellaneous others (n = 3). An additional 35 subjects (3 percent) were not residents of the County in 1988 and were therefore ineligible (4, 5). A letter was sent to all eligible subjects (n — 1,021), outlining the study and requesting their participation. Included with the letter was the bowel disease questionnaire, which has been shown to be an understandable, easily completed, and highly reliable instrument (median kappa for individual symptom items = 0.78; range, 0.52-1.0) in the outpatient setting; it has also been demonstrated to have adequate content and predictive and construct validity (10, 11, 13). The questionnaire consists of 46 gastrointestinal symptom-related items; 25 items that measure past illness, health care use, and sociodemographic variables; and a valid measure of nongastrointestinal somatic complaints, the Psychosomatic Symptom Checklist (14, 15). Reminder letters were sent as needed after 2 weeks, 4 weeks, and 7 weeks to nonresponders. The remaining persons were then telephoned at 10 weeks. Subjects who indicated at any point that they did not wish to participate were not contacted further. A
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completed questionnaire was returned by 835 subjects, giving a response rate of 82 percent (4, 5). The bowel disease questionnaire was remailed to the responders who were alive 1220 months later (three men had died in the interim). The questionnaire contained all of the symptom item questions but was briefer, as past illness questions and the Psychosomatic Symptom Checklist were omitted. A total of 690 subjects returned a completed questionnaire, giving a response rate of 83 percent.
Symptom categories
Subjects were classified into several a priori symptom groups based on their responses to the questionnaire, which recorded their symptoms over the previous year. Frequent abdominal pain. Persons who reported having had more than six episodes of abdominal pain in the prior year were considered to have frequent abdominal pain; those who reported fewer episodes were not included in this category in order to remove those experiencing only gastroenteritis or other acute illnesses (4, 5). Symptoms compatible with the irritable bowel syndrome. Two different definitions of irritable bowel syndrome were applied. First, persons who experienced frequent abdominal pain in combination with two or more of the following Manning symptom criteria were considered to have the irritable bowel syndrome: 1) pain that was often (more than 25 percent of the time) relieved by defecation; 2) looser stools often when pain began; 3) more frequent stools often when pain began; 4) abdominal distension often; 5) a feeling of incomplete evacuation often; and 6) mucus from the rectum. It has been shown that the more of these criteria that are present, the higher the probability of the irritable bowel syndrome (8, 9). A second definition comprised the modified Rome criteria for irritable bowel syndrome, based on the consensus of an international panel of clinical investigators (2). The criteria used in this study were the following:
168
Talleyetal.
colonic pain (frequent lower abdominal pain often relieved by defecation and/or associated with looser and/or more frequent stools at its onset) in combination with three or more of 1) altered stool frequency (less than three stools per week or more than three stools daily, often), 2) altered stool form (hard or loose/watery stool, often), 3) altered stool passage (straining or urgency or a feeling of incomplete evacuation, often), 4) passage of mucus, and 5) abdominal distension, often (2). Chronic constipation. Subjects who often strained at stool and passed hard stools and/ or those whose stool frequency was often less than three stools per week were defined as having chronic constipation (4). Chronic diarrhea. Subjects who described their usual bowel habit as diarrhea and who reported loose, watery stools often and/or subjects whose stool frequency was often more than three stools per day were defined as having chronic diarrhea. This is a more restrictive definition than has been used previously (4). Dyspepsia. This was defined as abdominal pain in the prior year that was centered in the upper abdomen; frequent dyspepsia was considered to be present if pain occurred more than six times in the prior year (5, 16). Subjects who reported heartburn and/or acid regurgitation once a week or more were considered to have frequent gastroesophageal reflux (5); it has been demonstrated that, when these are the dominant symptoms, they correlate with objective evidence of pathologic acid reflux (16, 17). Statistical analysis
The prevalence of gastrointestinal symptoms in Olmsted County was originally estimated using the entire first sample (4, 5). The overall age- and sex-adjusted prevalence rates (per 100) among survey respondents were obtained by directly adjusting the ageand sex-observed proportions from both the first (n = 835) and second surveys (n = 690) to the population structure of 1980 US whites aged 30-64 years (18). Symptom on-
set and disappearance per 1,000 personyears of observation were calculated using the date that the initial survey was returned and the date of return for the second survey. Onset rates were based on those free of symptoms at the time of the initial survey who reported having symptoms on the second survey; this was not considered a true "incidence" rate because subjects could have had the symptoms in the distant past (i.e., more than a year before the first survey). Likewise, rates of disappearance were based on those reporting symptoms at the time of the first survey who were free of symptoms on the second survey. Ninety-five percent confidence intervals were calculated based on the binomial distribution. Data from the first survey were used to estimate the possible effects of responder bias in the second survey using a logistic regression analysis to identify variables associated with nonresponse (no/yes). Several variables were selected a priori as potentially associated with nonresponse: 1) age; 2) sex; 3) marital status; 4) "complainers" (a somatization score based on how frequent and/or bothersome 12 nongastrointestinal symptoms from the Psychosomatic Symptom Checklist had been in the last year, subjects were classified as "complainers" if their combined frequency and bothersome scores were greater than the median score for all subjects); 5) doctor visits (seeking health care for either "belly aches" or "problems with bowels"); 6) previous gastrointestinal surgery (cholecystectomy, appendectomy, other abdominal operations); and 7) a history of abdominal pain as a child. A logistic regression analysis, adjusting for age and sex, was used to assess whether the time between returned surveys and these a priori variables were associated with either the onset or disappearance of each of the major symptom categories described above. The onset and disappearance rates per 1,000 person-years for each of the major symptom categories were estimated separately for strata defined by these factors. The alpha level of significance was set at 0.05; all p values calculated were two tailed.
Gastrointestinal Symptoms
RESULTS Prevalence, onset, and disappearance of symptoms
The overall age- and sex-adjusted prevalence rates of individual symptoms are presented for the first and second surveys in table 1. The prevalence rates were not significantly different in the two surveys. Of
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the 690 subjects who responded to both surveys, the reporting of the presence and absence of symptoms did not change in the majority of cases (table 2). The onset and disappearance rates per 1,000 person-years of observation for the individual gastrointestinal symptom items are presented in table 3. Although the two surveys were mailed to the subjects 12-20 months apart, the median
TABLE 1. Prevalence (per 100) of individual gastrointestinal symptom Items In 30- to 64-year-old CXmsted County, Minnesota, residents in both surveys, 1988-1991 First survey (n = 835)
Symptom
Second survey (n- •690)
Prevalence*
95% Clf
Prevalence*
95% Cl
Abdominal pain Abdominal pain Pain severe or very severe usuaty Night pain Periodic pain Pain once a week or more Pain lasting ±30 minutes usually Pain >10 years Pain before meals often}; Pain immediately after meals often Pain from 30 minutes to 2 hours after meals often Pain relieved by belching often Pain relieved by defecation often Pain relieved by eating often Pain relieved by antacids often Pain aggravated by food or milk often Pain aggravated by alcohol often Pain radiates outside abdomen often More frequent stools at pain onset often Looser stools at pain onset often
46.6 7.6 14.3 29.0 11.8 28.2 11.6 6.6 10.1 21.4 16.2 28.4 6.6 18.8 11.3 7.9 7.5 175 22.1
43.2-50.0 5.8-9.4 11.9-16.7 25.8-32.1 9.6-14.0 25.1-31.3 9.4-13.7 4.8-8.3 8.0-12 1 18.6-24 3 13.6-18.7 25.3-31.5 6.7-10.5 16.1-21.5 9.1-13.5 6.0-9.7 5.6-9.3 14.9-20.1 19.2-25.0
46.8 5.5 13.6 29.3 11.2 26.2 13.6 6.6 8.9 21.2 12.8 28.9 7.8 17.2 11.1 7.5 5.4 18.5 21.7
43.1-50.6 3.7-7.2 11.0-16.3 25.8-32.8 8.8-13.7 22.8-29.6 11.0-16.2 4.7-8.6 6.7-11.1 18.0-24.4 10.3-15.4 25.4-32.4 5.7-9.9 14.3-20.1 8.7-13.5 5.4-9.6 3.7-7.2 15.5-21.5 18.5-24.9
Disturbed defecation Bowel habit altered in last year Bowel pattern described as abnormal usually One or less stools passed weekly 22 or more stools passed weekly Takes laxatives, bran, fiber Mucus in stools 3 stools daly often Straining at stool often Loose/watery stools often Hard stools often Feeling of incomplete evacuation often Urgency often Blood in stools or toilet bowl
8.4 17.6 0.8 0.9 15.7 16.3 6.0 3.9 18.5 16.3 24.1 21.5 18.7 14.2
6.5-10.4 14.9-20.2 0.2-1.5 0.2-1.5 13.2-18.2 13.7-18.9 4.3-7.6 2.6-5.2 15.9-21.2 13.8-18.8 21.1-27.1 18.6-24.3 16.0-21.3 11.8-16.7
8.3 17.1 0.7 0.9 14.1 17.8 4.4 4.6 17.6 18.5 23.2 24.0 187 13.9
6.2-10.4 14.2-20.0 0.0-1.4 0.2-1.6 11.6-16.6 14.8-20.8 2.8-5.9 3.0-6.2 14.7-20.6 15.6-21.5 19.9-26.4 20.7-27.2 15.7-21.7 11.2-16.6
Other gastrointestinal symptoms Nausea once a month or more Vomiting once a month or more Bloating (visible distension) often Difficulty swallowing often Heartburn once a month or more Heartburn several times a week or daily Acid regurgitation once a month or more Weight loss a7 pounds Loss of appetite
7.4 2.3 20.8 6.9 24.4 6.8 11.3 2.9 4.0
5.6-9.2 1.3-3.3 18.0-23.5 5.2-8.7 21.5-27.4 5.1-8.5 9.1-13.5 1.8-3.9 2.7-5.3
5.2 1.4 20.1 6.3 20.0 6.0 9.6 1.9 3.9
3.5-6.9 0.5-2.3 17.0-23.1 4.5-8.2 17.0-23.1 4.2-7.8 7.4-11.9 0.9-2.9 2.5-5.4
• Directly age and sex adjusted to the population structure of US whites In 1980. t Cl, confidence Interval. t Often, >25% of the time.
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Talleyetal.
TABLE 2. Proportion of the 690 responders whose reporting of symptoms did not change over the 12-20 months: Olmsted County, Minnesota, 1988-1991 Symptom category
Frequent abdominal pain Manning criteria (22) for IBS* Rome criteria (23) for IBS Pain relieved by defecation oftenf Looser stools at pain onset often More frequent stools at pain onset often Feeling of incomplete evacuation often Bloating (visible distension) often Mucus in stools Altered stool frequency Altered stool form Altered stool passage Colonic pain Chronic constipation Chronic diarrhea Frequent dyspepsia
% unchanged
82 86 93 70 69 70 83 83 88 92 78 78 88 89 94 86
• IBS, Irritable bowel syndrome, t Often, >25% of the time.
time between returned surveys was 14.6 months, with an interquantile range of 12.520.5 months. Frequent abdominal pain. A total of 217 subjects reported frequent abdominal pain for an age- and sex-adjusted prevalence rate of 26.2 per 100 (95 percent confidence interval (Cl) 23.1-29.2) using data from the first survey; in the second survey, 24.8 per 100 (95 percent CI 21.5-28.1) had frequent pain. The onset rate (per 1,000 person-years) of frequent abdominal pain was 85, while the disappearance rate (per 1,000 personyears) was 270 among subjects previously reporting the symptom. The onset and disappearance rates for frequent abdominal pain by age are presented in figures 1 and 2. Symptoms compatible with the irritable bowel syndrome. In the first sample, 140 subjects had frequent abdominal pain and two or more of the Manning criteria for the irritable bowel syndrome, for an age- and sex-adjusted prevalence rate of 17.0 per 100 (95 percent CI 14.4-19.6). In the second survey, the prevalence was 18.1 per 100 (95 percent CI 15.1-21.1). Using the Rome criteria, 58 subjects had irritable bowel syn-
drome symptoms in the first survey; the ageand sex-adjusted prevalence rates in the first and second surveys were 7.2 (95 percent CI 5.4-9.0) and 8.0 (95 percent CI 5.8-10.1) per 100, respectively. The onset rates of the irritable bowel syndrome using the Manning and Rome criteria were 67 and 28, while the disappearance rates were 280 and 352, respectively, per 1,000 person-years. The onset and disappearance rates for the irritable bowel syndrome (using the Manning criteria) by age are presented in figures 1 and 2. Chronic constipation and diarrhea. A total of 140 subjects reported chronic constipation, while 50 subjects reported chronic diarrhea, for age- and sex-adjusted prevalence rates of 17.4 per 100 (95 percent CI 14.820.0) and 6.0 per 100 (95 percent CI 4.47.7), respectively, using data from the first survey; second survey rates were 14.7 (95 percent CI 11.9-17.4) and 7.3 (95 percent CI 5.3-9.3) per 100, respectively. The onset rates (per 1,000 person-years) of constipation and diarrhea were 40 and 29 with disappearance rates of 309 and 282 (per 1,000 person-years), respectively. The onset and disappearance rates for constipation and diarrhea by age are presented in figures 1 and 2. Dyspepsia and gastroesophageal reflux. Of those with abdominal pain, 132 subjects had frequent dyspepsia for an age- and sexadjusted prevalence rate of 15.7 per 100 (95 percent CI 13.2-18.2) using data from the first survey; the prevalence was 14.1 per 100 (95 percent CI 11.5-16.8) using data from the second survey. The onset rate (per 1,000 person-years) of frequent dyspepsia was 56; this was countered by a loss of the symptom in 352 cases per 1,000 person-years. The onset and disappearance rates for frequent dyspepsia by age are presented in figures 1 and 2. A total of 125 subjects reported frequent (> once weekly) heartburn and/or acid regurgitation in the first survey; the ageand sex-adjusted prevalence rates were 15.0 (95 percent CI 12.5-17.4) and 12.3 (95 percent CI 9.8-14.8) per 100, respectively, on the two surveys. The onset (per 1,000 person-years) of frequent gastroesophageal reflux was estimated to be 43, while the
Gastrointestinal Symptoms
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TABLE 3. Onset and disappearance of individual gastrointestinal symptoms in 30- to 64-year-old Olmsted County, Minnesota, residents (n = 690), 1988-1991 Onset
Disappearance
Cumulative rate (%)
Rate per 1,000 person-years
Abdominal pain Abdominal pain Pain severe or very severe usually Night pain Periodic pain Pain once a week or more Pain lasting £30 minutes usually Pain >10 years Pain before meals often* Pain Immediately after meate often Pain from 30 minutes to 2 hours after meals often Pain relieved by betehlng often Pain reieved by defecation often Pain reieved by eating often PainreSevedby antacids often Pain aggravated by food or milk often Pain aggravated by alcohol often Pain radiates outside abdomen often More frequent stools at pain onset often Looser stools at pain onset often
19.6 3.4 6.4 16.2 6.4 13.4 8.1 3.7 5.1 12.2 6.7 15.2 4.1 6.6 7.1 3.6 3.6 10.1 11.0
143.7 25.1 46.6 118.0 47.1 98.4 59.1 27.1 37.3 89.4 49.2 112.1 30.1 47.8 51.8 26.7 26.4 73.7 79.9
23.4 70.8 41.1 40.3 54.3 40.2 46.3 57.8 61.8 52.0 55.1 41.0 55.9 32.6 54.6 46.9 72.6 46.0 46.2
172.0 530.4 311.0 301.4 386.3 290.9 336.3 453.8 449.3 383.1 402.9 294.7 430.8 240.8 393.6 341.7 536.8 336.1 345.3
Disturbed defecation Bowel habit altered In last year Bowel pattern described as abnormal usually One or less stools passed weekly 22 or more stools passed weekly Takes laxatives, bran, ftoer Mucus In stools 3 stools daily often Straining at stool often Loose/watery stools often Hard stools often Feeling of Incomplete evacuation often Urgency often Blood In stools or toilet bowl
6.1 7.1 0.3 04 6.2 7.5 1.5 2.7 8.2 9.7 9.4 11.4 9.5 6.4
44.7 52.2 2.1 3.2 45.3 54.7 11.3 20.0 60.0 70.6 68.4 83.6 68.9 47.1
65.5 34.2 33.3 50.0 37.7 34.3 47.2 51.9 41.8 37.7 352 31.5 42 3 43.0
463.9 252.2 225.6 384.2 276.5 261.2 367.3 373.3 303.2 276.5 259.3 232.8 318.1 303.2
2.6 0.8 9.2 3.1 6.9 2.7 5.3 1.8 3.4
19.4 5.5 67.5 22.8 50.2 196 385 13.2 24.5
59.5 73.3 33.1 39.5 38.1 47.8 52.0 85.0 71.4
426.5 581.6 243.5 298.8 282.7 331.1 395.3 607.6 529.4
Symptom
Other gastrointestinal symptoms Nausea once a month or more Vomiting once a month or more Bloating (vlstole distension) often Difficulty swallowing often Heartburn once a month or more Heartburn several tmes a week or dally Acid regurgttabon once a month or more Weight loss a7 pounds Loss of appetite
Cumulative rate (%)
Rate per 1,000 person-years
• Often, >25% of the time.
disappearance rate (per 1,000 person-years) was 353. Of those with frequent gastroesophageal reflux symptoms on the first survey, 51 percent also reported frequent dyspepsia. Response bias
Based on data from the first survey, the responders and nonresponders to the second survey were analyzed to determine whether there were any question items that predicted
nonresponse to the second survey. In the logistic regression analysis, the variables age and sex were included at the first step. Although several individual questions were significant univariately, a joint simultaneous test for all candidate variables based on the residual chi-square test was not significant (p>0.15). Seven variables were identified a priori as potential factors that might have been associated with nonresponse to the second sur-
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Talleyetal. Chronic constipalion Chronic diarrhea Frequent dyspepsia IBS (Manning criteria) Frequent abdominai pain
100 90
I
80
o.
70
8
60
o
50 40 30
,
400
CD C O O
360
C CO
—
— —
Chronic constipation Chronic diarrhea Frequent dyspepsia IBS (Manning criteria) Frequent abdominal pain
320 CO Q. CD 280 Q. Q. CO 240 CO 200
40-49
50-59
60-64
Age group, yr FIGURE 2. Disappearance rate per 1,000 person-years by age for chronic constipation, chronic diarrhea, frequent dyspepsia, the irritable bowel syndrome (IBS, £2 Manning criteria), and frequent abdominal pain: Olmsted County, Minnesota, 1988-1991.
vey. Three of these variables retained significance when analyzed multivariately: age, complainer score, and marital status. In particular, the 145 nonresponders were younger (median, 44 vs. 48 years), more likely to be classified as a "complainer" (i.e., those who tended to have multiple nongastrointestinal somatic symptoms, 57 percent vs. 48 percent), and unmarried (24 percent vs. 14 percent) in comparison with the responders. To determine the influence of these vari-
ables on the onset rates, the rates per 1,000 person-years for each of the symptom categories described previously were estimated separately by stratifying for each of the variables (table 4). The subjects who fell into the "complainer" category generally had a higher onset of gastrointestinal symptoms than did "noncomplainers." It should be noted that, since the odds of not responding were 1.4 times higher for "complainers" than "noncomplainers," the onset rates for
83.9 (62.3-105.6) 91.9 (35.5-146.8)
124.4* (87.9-160.9) 55.9 (34.0-77.9)
Married Yes No
Com plainer Yes No
* Significantly associated with developing the symptom (p < 0.05). f IBS, Irritable bowel syndrome. t Total person-years for the subjects at risk. § Numbers in parentheses, 95% confidence Interval.
67.8 (42.0-93.7) 101.5 (70.7-132.3)
95.9 (62.8-129.0) 76.8 (51.6-102.0)
708.6 84.7 (64.5-104.8)§
Frequent abdominal pain
Sex Male Female
Age 45 years or younger Over 45 years
Total person-yearstOverall
Variables associated with nonresponse
82.5*'(54.2-110.8) 54.1 (33.2-74.9)
69.2 (50.4-88.0) 52.8 (12.1-93.4)
60.4 (37.3-83.6) 72.9 (47.7-98.0)
85.2 (55.0-115.4) 54.3 (34.2-74.4)
795.3 66.6 (49.5-83.7)
IBSf (Manning criteria a2 symptoms)
52.4(29.7-75.1) 30.2(14.1-46.3)
41.4 (26.5-56.3) 35.0 (1.5-68.5)
40.1 (21.0-59.3) 40.6 (21.3-59.9)
50.3* (29.6-71.1) 10.6 (1.4-19.8)
25.0 (13.9-36.0) 55.9* (16.1-95.6)
36.5 (19.1-53.9) 22.2 (8.7-35.8)
32.7 (14.6-50.8) 26.8 (13.0-40.6)
888.4 29.3 (18.2-40.3)
792.7 40.4 (26.8-54.0) 53.6(29.0-78.1) 31.6(15.9-47.2)
Chronic diarrhea
Chronic constipation
Symptom categories (onset/1,000 person-years)
80.4''(52.8-108.1) 36.2 (18.9-53.5)
52.6 (36.0-69.1) 78.0 (29.9-126.2)
44.0 (23.7-64.3) 67.3 (43.5-91.0)
62.6 (37.0-88.3) 51.4 (31.6-71.2)
802.3 56.1 (40.3-71.8)
Frequent dyspepsia
TABLE 4. Onset/1,000 person-years of the main symptom categories stratified by variables associated with nonresponse In Olmsted County, Minnesota, residents, 1988-1991
en
I
227.6 (148.1-307.1) 300.6 (230.4-370.8)
193.4 (122.4-264.4) 337.5* (262.6-412.3)
270.0 (212.7-327.3) 272.4 (131.7-413.2)
278.1 (214.3-341.8) 252.8 (157.4-348.1)
Age 45 years or younger Over 45 years
Sex Male Female
Married Yes No
Com plainer Yes No
• Significantly associated with the disappearance of the symptom (p < 0.05). t IBS, irritable bowel syndrome. i Total person-years for the subjects at risk. § Numbers In parentheses, 95% confidence Interval.
297.0 (217.6-376.4) 233.5 (106.8-360.1)
257.5 (186.7-328.2) 441.7 (241.3-642.0)
199.2 (106.4-292.1) 345.5*1 (252.8-438.3)
279.3(195.3-363.2) 363.6 (249.6-477.7)
304.7 (232.0-377.3) 340.1 (140.4-539.8)
359.6 (255.7-463.5) 270.7(181.8-359.7)
322.6 (222.7-422.5) 296.3 (202.7-389.8)
148.9 308.9 (240.6-377.2)
146.3 280.3 (212.7-347.8)
233.1 270.3 (217.3-323.4)§
Total person-years}: Overall 250.8 (155.8-345.9) 308.6 (213.7-403.5)
Chronic constipation
IBSf (Manning criteria a2 symptoms)
286.4(160.9-412.0) 266.0 (20.2-511.7)
235.9(121.2-350.3) 611.8(343.7-879.9)
209.1 (55.1-363.1) 341.7(185.3-498.1)
354.6 (270.4-438.8) 344.6 (212.7-476.4)
358.1 (282.4-433.7) 303.9 (100.4-507.3)
261.5 (169.2-353.9) 461.3*1 (361.2-561.4)
337.3 (222.0-453.4) 360.3 (270.6-450.0)
139.4 351.7 (280.7^*22.6)
53.2 282.1 (170.1-394.1) 274.8(101.0-448.7) 287.1 (140.8-433.5)
Frequent dyspepsia
Chronic diarrhea
Symptom categories (onset/1 • 0 0 ° person-years)
Frequent abdominal pain
Variables associated with nonresponse
TABLE 5. Disappearance per 1,000 person-years oi the main symptom categories stratified by variables associated with nonresponse In Olmsted County, Minnesota, residents, 1988-1991
CD
CT •
Vol. 136, No. 2 Printed in U.S.A.
Onset and Disappearance of Gastrointestinal Symptoms and Functional Gastrointestinal Disorders
Nicholas J. Talley,1* Amy L. Weaver,2 Alan R. Zinsmeister,2 and L. Joseph Melton I
Functional gastrointestinal disorders, including the irritable bowel syndrome, account for up to 40% of referrals to gastroenterologists, but accurate data on the natural history of these disorders in the general population are lacking. Using a reliable and valid questionnaire, the authors estimated the onset and disappearance of symptoms consistent with functional gastrointestinal disorders. An age- and sex-stratified random sample of 1,021 eligible residents of Olmsted County, Minnesota, aged 30-64 years were initially mailed the questionnaire; 82% responded (n = 835). In a remailing to responders 12-20 months later, 83% responded again (n = 690). The age- and sexadjusted prevalence rates per 100 for irritable bowel syndrome, chronic constipation, chronic diarrhea, and frequent dyspepsia were 18.1 (95% confidence interval (Cl) 15.121.1), 14.7 (95% Cl 11.9-17.4), 7.3 (95% Cl 5.3-9.3), and 14.1 (95% Cl 11.5-16.8), respectively, on the second mailing. Symptoms were not significantly associated with nonresponse to the second mailing; moreover, the estimated prevalence rates were not significantly different from the first mailing. Among the 582 subjects free of the irritable bowel syndrome on the first survey, 9% developed symptoms during 795 person-years of follow-up, while 38% of the 108 who initially had the irritable bowel syndrome did not meet the criteria after 146 person-years of follow-up. Similar onset and disappearance rates were observed for the other main symptom categories. While functional gastrointestinal symptoms are common in middle-aged persons and overall prevalence appears relatively stable over 12-20 months, substantial turnover is implied by the observed onset and disappearance rates; several potential sources of bias do not seem to account for this variation. Am J Epidemiol 1992;136:165-77. colonic diseases, functional; constipation; diarrhea; dyspepsia; gastroenterology; gastroesophageal reflux; prevalence; questionnaires
The functional gastrointestinal disorders represent a group of conditions characterized by chronic or recurrent gastrointestinal symptoms that cannot be explained by structural or biochemical abnormalities (1).
These disorders are important because they are highly prevalent in the general population and have a significant impact on health care, yet epidemiologic studies of these problems remain sparse (1, 2). Up to 40 percent of referrals to gastroenterologists are for functional gastrointestinal problems (1, 2). In 1985, it was estimated that there were 4.2 million office visits for functional bowel disorders in the United States; over 2.2 million medications were prescribed (3). Yet, this is probably a gross underestimate of the problem. In a population-based study, Talley et al. have reported that approximately one quarter of the middle-aged Caucasians sampled had symptoms consistent with func-
Received for publication June 25, 1991, and In final form January 24, 1992. Abbreviation: Q, confidence internal. ' Division of Gastroenterology and Internal Medicine, Mayo Clinic and Foundation, Rochester, MN. i Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, MN. Reprint requests to Dr. Nicholas J. Talley, Gastroenterology Unit, Mayo dine, Rochester, MN 55905. This work was supported by the Rochester Epidemiology Project (AR 30582) from the National Institutes of Health and by a research grant from Glaxo.
165
166
Talleyetal.
tional gastrointestinal disorders, although most did not seek care (4, 5), confirming the results of studies of volunteers and other nonpatient groups (6, 7). However, there remain substantial gaps in our knowledge. Thus, it is uncertain whether the prevalence of functional gastrointestinal symptoms is stable or not. How often functional gastrointestinal symptoms develop in persons in the general population previously free of complaints is also unknown, and it is unclear whether persons who do develop such symptoms in the community continue to have them for prolonged periods. The commonest of the functional gastrointestinal disorders is the irritable bowel syndrome, which is characterized by abdominal pain usually associated with a chronic but erratic disturbance of defecation (I, 2). There is evidence that the standard medical history, when carefully obtained, can strongly point to the irritable bowel syndrome rather than organic disease being the diagnosis. Manning et al. (8) first reported that six symptoms could discriminate the irritable bowel syndrome from organic gastrointestinal disease in outpatients; the presence of two or more of these symptoms had a sensitivity and specificity of 94 percent and 55 percent, respectively, for identifying the syndrome (8). The discriminant value of these symptoms has subsequently been confirmed; we determined that the Manning criteria score had a sensitivity of 70 percent and specificity of 90 percent for discriminating pain-predominant irritable bowel syndrome from health (9). Diagnostic criteria based on the consensus of a panel of clinical investigators have also been developed (referred to as the Rome criteria), although their clinical utility has not been established (1,2). We have previously reported on the development of a reliable and valid self-report questionnaire for the measurement of functional gastrointestinal symptoms (10, 11), and we have obtained population-based data on a well-characterized random sample of middle-aged persons residing in Olmsted County (4, 5). We aimed to restudy this sample of the Olmsted County population,
using a similar questionnaire, in order to determine the stability of the prevalence rates and to estimate the onset and disappearance of individual gastrointestinal symptoms and symptom categories (including abdominal pain, irritable bowel syndrome, chronic constipation, chronic diarrhea, and dyspepsia). MATERIALS AND METHODS Subjects
Approval was provided by the Institutional Review Board of the Mayo Clinic in April 1987 to contact inhabitants of Olmsted County, Minnesota. The Olmsted County population comprises approximately 100,000 persons of which 98 percent are white; sociodemographically, the community is similar to the United States white population. Mayo Clinic is the major provider of medical care for this population. It has been determined previously that about 15 percent of all Mayo Clinic registrations are from the local population and that, each year, over half of the County population is seen at one of the Clinic facilities. During any given 4-year period, over 95 percent of local residents will have had at least one medical contact with a local care provider. An important feature of the Rochester environment is that each of these providers uses a dossier (or unit record) system, whereby all medical information for each individual is accumulated in a single record. The pertinent clinical data are accessible because the Mayo Clinic has maintained, since 1910, extensive indices based on clinical and histologic diagnoses and surgical procedures. The system was further developed by the Rochester Epidemiology Project (12), which created similar indices for the records of the other providers of medical care to residents of Rochester and Olmsted County. The Rochester Epidemiology Project medical records linkage system therefore provides what is essentially an enumeration of the population from which samples can be drawn. Using this system, we randomly selected 1,120 persons living in Olmsted County as of 1988 who were aged 30-64
Gastrointestinal Symptoms
years and stratified by age (in 5-year intervals) and sex (equal numbers of men and women). The study population should have been, therefore, a representative sample of Olmsted County residents 30-64 years of age.
Survey
Initially, the medical records of candidate subjects were reviewed. Sixty-four subjects (6 percent) were excluded because they were non-Caucasians (n = 16); had been diagnosed as having a major psychotic episode or dementia (n = 15); had undergone major abdominal surgery comprising nephrectomy (n = 5), renal transplant (n = 2), or bowel resection (« = 9) in the past; or currently had a major organic medical disease including active cancer (n = 7), ulcerative colitis (n = 1), severe congestive heart failure or valvular heart disease (n = 4), severe coronary artery disease (n = 2), or miscellaneous others (n = 3). An additional 35 subjects (3 percent) were not residents of the County in 1988 and were therefore ineligible (4, 5). A letter was sent to all eligible subjects (n — 1,021), outlining the study and requesting their participation. Included with the letter was the bowel disease questionnaire, which has been shown to be an understandable, easily completed, and highly reliable instrument (median kappa for individual symptom items = 0.78; range, 0.52-1.0) in the outpatient setting; it has also been demonstrated to have adequate content and predictive and construct validity (10, 11, 13). The questionnaire consists of 46 gastrointestinal symptom-related items; 25 items that measure past illness, health care use, and sociodemographic variables; and a valid measure of nongastrointestinal somatic complaints, the Psychosomatic Symptom Checklist (14, 15). Reminder letters were sent as needed after 2 weeks, 4 weeks, and 7 weeks to nonresponders. The remaining persons were then telephoned at 10 weeks. Subjects who indicated at any point that they did not wish to participate were not contacted further. A
167
completed questionnaire was returned by 835 subjects, giving a response rate of 82 percent (4, 5). The bowel disease questionnaire was remailed to the responders who were alive 1220 months later (three men had died in the interim). The questionnaire contained all of the symptom item questions but was briefer, as past illness questions and the Psychosomatic Symptom Checklist were omitted. A total of 690 subjects returned a completed questionnaire, giving a response rate of 83 percent.
Symptom categories
Subjects were classified into several a priori symptom groups based on their responses to the questionnaire, which recorded their symptoms over the previous year. Frequent abdominal pain. Persons who reported having had more than six episodes of abdominal pain in the prior year were considered to have frequent abdominal pain; those who reported fewer episodes were not included in this category in order to remove those experiencing only gastroenteritis or other acute illnesses (4, 5). Symptoms compatible with the irritable bowel syndrome. Two different definitions of irritable bowel syndrome were applied. First, persons who experienced frequent abdominal pain in combination with two or more of the following Manning symptom criteria were considered to have the irritable bowel syndrome: 1) pain that was often (more than 25 percent of the time) relieved by defecation; 2) looser stools often when pain began; 3) more frequent stools often when pain began; 4) abdominal distension often; 5) a feeling of incomplete evacuation often; and 6) mucus from the rectum. It has been shown that the more of these criteria that are present, the higher the probability of the irritable bowel syndrome (8, 9). A second definition comprised the modified Rome criteria for irritable bowel syndrome, based on the consensus of an international panel of clinical investigators (2). The criteria used in this study were the following:
168
Talleyetal.
colonic pain (frequent lower abdominal pain often relieved by defecation and/or associated with looser and/or more frequent stools at its onset) in combination with three or more of 1) altered stool frequency (less than three stools per week or more than three stools daily, often), 2) altered stool form (hard or loose/watery stool, often), 3) altered stool passage (straining or urgency or a feeling of incomplete evacuation, often), 4) passage of mucus, and 5) abdominal distension, often (2). Chronic constipation. Subjects who often strained at stool and passed hard stools and/ or those whose stool frequency was often less than three stools per week were defined as having chronic constipation (4). Chronic diarrhea. Subjects who described their usual bowel habit as diarrhea and who reported loose, watery stools often and/or subjects whose stool frequency was often more than three stools per day were defined as having chronic diarrhea. This is a more restrictive definition than has been used previously (4). Dyspepsia. This was defined as abdominal pain in the prior year that was centered in the upper abdomen; frequent dyspepsia was considered to be present if pain occurred more than six times in the prior year (5, 16). Subjects who reported heartburn and/or acid regurgitation once a week or more were considered to have frequent gastroesophageal reflux (5); it has been demonstrated that, when these are the dominant symptoms, they correlate with objective evidence of pathologic acid reflux (16, 17). Statistical analysis
The prevalence of gastrointestinal symptoms in Olmsted County was originally estimated using the entire first sample (4, 5). The overall age- and sex-adjusted prevalence rates (per 100) among survey respondents were obtained by directly adjusting the ageand sex-observed proportions from both the first (n = 835) and second surveys (n = 690) to the population structure of 1980 US whites aged 30-64 years (18). Symptom on-
set and disappearance per 1,000 personyears of observation were calculated using the date that the initial survey was returned and the date of return for the second survey. Onset rates were based on those free of symptoms at the time of the initial survey who reported having symptoms on the second survey; this was not considered a true "incidence" rate because subjects could have had the symptoms in the distant past (i.e., more than a year before the first survey). Likewise, rates of disappearance were based on those reporting symptoms at the time of the first survey who were free of symptoms on the second survey. Ninety-five percent confidence intervals were calculated based on the binomial distribution. Data from the first survey were used to estimate the possible effects of responder bias in the second survey using a logistic regression analysis to identify variables associated with nonresponse (no/yes). Several variables were selected a priori as potentially associated with nonresponse: 1) age; 2) sex; 3) marital status; 4) "complainers" (a somatization score based on how frequent and/or bothersome 12 nongastrointestinal symptoms from the Psychosomatic Symptom Checklist had been in the last year, subjects were classified as "complainers" if their combined frequency and bothersome scores were greater than the median score for all subjects); 5) doctor visits (seeking health care for either "belly aches" or "problems with bowels"); 6) previous gastrointestinal surgery (cholecystectomy, appendectomy, other abdominal operations); and 7) a history of abdominal pain as a child. A logistic regression analysis, adjusting for age and sex, was used to assess whether the time between returned surveys and these a priori variables were associated with either the onset or disappearance of each of the major symptom categories described above. The onset and disappearance rates per 1,000 person-years for each of the major symptom categories were estimated separately for strata defined by these factors. The alpha level of significance was set at 0.05; all p values calculated were two tailed.
Gastrointestinal Symptoms
RESULTS Prevalence, onset, and disappearance of symptoms
The overall age- and sex-adjusted prevalence rates of individual symptoms are presented for the first and second surveys in table 1. The prevalence rates were not significantly different in the two surveys. Of
169
the 690 subjects who responded to both surveys, the reporting of the presence and absence of symptoms did not change in the majority of cases (table 2). The onset and disappearance rates per 1,000 person-years of observation for the individual gastrointestinal symptom items are presented in table 3. Although the two surveys were mailed to the subjects 12-20 months apart, the median
TABLE 1. Prevalence (per 100) of individual gastrointestinal symptom Items In 30- to 64-year-old CXmsted County, Minnesota, residents in both surveys, 1988-1991 First survey (n = 835)
Symptom
Second survey (n- •690)
Prevalence*
95% Clf
Prevalence*
95% Cl
Abdominal pain Abdominal pain Pain severe or very severe usuaty Night pain Periodic pain Pain once a week or more Pain lasting ±30 minutes usually Pain >10 years Pain before meals often}; Pain immediately after meals often Pain from 30 minutes to 2 hours after meals often Pain relieved by belching often Pain relieved by defecation often Pain relieved by eating often Pain relieved by antacids often Pain aggravated by food or milk often Pain aggravated by alcohol often Pain radiates outside abdomen often More frequent stools at pain onset often Looser stools at pain onset often
46.6 7.6 14.3 29.0 11.8 28.2 11.6 6.6 10.1 21.4 16.2 28.4 6.6 18.8 11.3 7.9 7.5 175 22.1
43.2-50.0 5.8-9.4 11.9-16.7 25.8-32.1 9.6-14.0 25.1-31.3 9.4-13.7 4.8-8.3 8.0-12 1 18.6-24 3 13.6-18.7 25.3-31.5 6.7-10.5 16.1-21.5 9.1-13.5 6.0-9.7 5.6-9.3 14.9-20.1 19.2-25.0
46.8 5.5 13.6 29.3 11.2 26.2 13.6 6.6 8.9 21.2 12.8 28.9 7.8 17.2 11.1 7.5 5.4 18.5 21.7
43.1-50.6 3.7-7.2 11.0-16.3 25.8-32.8 8.8-13.7 22.8-29.6 11.0-16.2 4.7-8.6 6.7-11.1 18.0-24.4 10.3-15.4 25.4-32.4 5.7-9.9 14.3-20.1 8.7-13.5 5.4-9.6 3.7-7.2 15.5-21.5 18.5-24.9
Disturbed defecation Bowel habit altered in last year Bowel pattern described as abnormal usually One or less stools passed weekly 22 or more stools passed weekly Takes laxatives, bran, fiber Mucus in stools 3 stools daly often Straining at stool often Loose/watery stools often Hard stools often Feeling of incomplete evacuation often Urgency often Blood in stools or toilet bowl
8.4 17.6 0.8 0.9 15.7 16.3 6.0 3.9 18.5 16.3 24.1 21.5 18.7 14.2
6.5-10.4 14.9-20.2 0.2-1.5 0.2-1.5 13.2-18.2 13.7-18.9 4.3-7.6 2.6-5.2 15.9-21.2 13.8-18.8 21.1-27.1 18.6-24.3 16.0-21.3 11.8-16.7
8.3 17.1 0.7 0.9 14.1 17.8 4.4 4.6 17.6 18.5 23.2 24.0 187 13.9
6.2-10.4 14.2-20.0 0.0-1.4 0.2-1.6 11.6-16.6 14.8-20.8 2.8-5.9 3.0-6.2 14.7-20.6 15.6-21.5 19.9-26.4 20.7-27.2 15.7-21.7 11.2-16.6
Other gastrointestinal symptoms Nausea once a month or more Vomiting once a month or more Bloating (visible distension) often Difficulty swallowing often Heartburn once a month or more Heartburn several times a week or daily Acid regurgitation once a month or more Weight loss a7 pounds Loss of appetite
7.4 2.3 20.8 6.9 24.4 6.8 11.3 2.9 4.0
5.6-9.2 1.3-3.3 18.0-23.5 5.2-8.7 21.5-27.4 5.1-8.5 9.1-13.5 1.8-3.9 2.7-5.3
5.2 1.4 20.1 6.3 20.0 6.0 9.6 1.9 3.9
3.5-6.9 0.5-2.3 17.0-23.1 4.5-8.2 17.0-23.1 4.2-7.8 7.4-11.9 0.9-2.9 2.5-5.4
• Directly age and sex adjusted to the population structure of US whites In 1980. t Cl, confidence Interval. t Often, >25% of the time.
170
Talleyetal.
TABLE 2. Proportion of the 690 responders whose reporting of symptoms did not change over the 12-20 months: Olmsted County, Minnesota, 1988-1991 Symptom category
Frequent abdominal pain Manning criteria (22) for IBS* Rome criteria (23) for IBS Pain relieved by defecation oftenf Looser stools at pain onset often More frequent stools at pain onset often Feeling of incomplete evacuation often Bloating (visible distension) often Mucus in stools Altered stool frequency Altered stool form Altered stool passage Colonic pain Chronic constipation Chronic diarrhea Frequent dyspepsia
% unchanged
82 86 93 70 69 70 83 83 88 92 78 78 88 89 94 86
• IBS, Irritable bowel syndrome, t Often, >25% of the time.
time between returned surveys was 14.6 months, with an interquantile range of 12.520.5 months. Frequent abdominal pain. A total of 217 subjects reported frequent abdominal pain for an age- and sex-adjusted prevalence rate of 26.2 per 100 (95 percent confidence interval (Cl) 23.1-29.2) using data from the first survey; in the second survey, 24.8 per 100 (95 percent CI 21.5-28.1) had frequent pain. The onset rate (per 1,000 person-years) of frequent abdominal pain was 85, while the disappearance rate (per 1,000 personyears) was 270 among subjects previously reporting the symptom. The onset and disappearance rates for frequent abdominal pain by age are presented in figures 1 and 2. Symptoms compatible with the irritable bowel syndrome. In the first sample, 140 subjects had frequent abdominal pain and two or more of the Manning criteria for the irritable bowel syndrome, for an age- and sex-adjusted prevalence rate of 17.0 per 100 (95 percent CI 14.4-19.6). In the second survey, the prevalence was 18.1 per 100 (95 percent CI 15.1-21.1). Using the Rome criteria, 58 subjects had irritable bowel syn-
drome symptoms in the first survey; the ageand sex-adjusted prevalence rates in the first and second surveys were 7.2 (95 percent CI 5.4-9.0) and 8.0 (95 percent CI 5.8-10.1) per 100, respectively. The onset rates of the irritable bowel syndrome using the Manning and Rome criteria were 67 and 28, while the disappearance rates were 280 and 352, respectively, per 1,000 person-years. The onset and disappearance rates for the irritable bowel syndrome (using the Manning criteria) by age are presented in figures 1 and 2. Chronic constipation and diarrhea. A total of 140 subjects reported chronic constipation, while 50 subjects reported chronic diarrhea, for age- and sex-adjusted prevalence rates of 17.4 per 100 (95 percent CI 14.820.0) and 6.0 per 100 (95 percent CI 4.47.7), respectively, using data from the first survey; second survey rates were 14.7 (95 percent CI 11.9-17.4) and 7.3 (95 percent CI 5.3-9.3) per 100, respectively. The onset rates (per 1,000 person-years) of constipation and diarrhea were 40 and 29 with disappearance rates of 309 and 282 (per 1,000 person-years), respectively. The onset and disappearance rates for constipation and diarrhea by age are presented in figures 1 and 2. Dyspepsia and gastroesophageal reflux. Of those with abdominal pain, 132 subjects had frequent dyspepsia for an age- and sexadjusted prevalence rate of 15.7 per 100 (95 percent CI 13.2-18.2) using data from the first survey; the prevalence was 14.1 per 100 (95 percent CI 11.5-16.8) using data from the second survey. The onset rate (per 1,000 person-years) of frequent dyspepsia was 56; this was countered by a loss of the symptom in 352 cases per 1,000 person-years. The onset and disappearance rates for frequent dyspepsia by age are presented in figures 1 and 2. A total of 125 subjects reported frequent (> once weekly) heartburn and/or acid regurgitation in the first survey; the ageand sex-adjusted prevalence rates were 15.0 (95 percent CI 12.5-17.4) and 12.3 (95 percent CI 9.8-14.8) per 100, respectively, on the two surveys. The onset (per 1,000 person-years) of frequent gastroesophageal reflux was estimated to be 43, while the
Gastrointestinal Symptoms
171
TABLE 3. Onset and disappearance of individual gastrointestinal symptoms in 30- to 64-year-old Olmsted County, Minnesota, residents (n = 690), 1988-1991 Onset
Disappearance
Cumulative rate (%)
Rate per 1,000 person-years
Abdominal pain Abdominal pain Pain severe or very severe usually Night pain Periodic pain Pain once a week or more Pain lasting £30 minutes usually Pain >10 years Pain before meals often* Pain Immediately after meate often Pain from 30 minutes to 2 hours after meals often Pain relieved by betehlng often Pain reieved by defecation often Pain reieved by eating often PainreSevedby antacids often Pain aggravated by food or milk often Pain aggravated by alcohol often Pain radiates outside abdomen often More frequent stools at pain onset often Looser stools at pain onset often
19.6 3.4 6.4 16.2 6.4 13.4 8.1 3.7 5.1 12.2 6.7 15.2 4.1 6.6 7.1 3.6 3.6 10.1 11.0
143.7 25.1 46.6 118.0 47.1 98.4 59.1 27.1 37.3 89.4 49.2 112.1 30.1 47.8 51.8 26.7 26.4 73.7 79.9
23.4 70.8 41.1 40.3 54.3 40.2 46.3 57.8 61.8 52.0 55.1 41.0 55.9 32.6 54.6 46.9 72.6 46.0 46.2
172.0 530.4 311.0 301.4 386.3 290.9 336.3 453.8 449.3 383.1 402.9 294.7 430.8 240.8 393.6 341.7 536.8 336.1 345.3
Disturbed defecation Bowel habit altered In last year Bowel pattern described as abnormal usually One or less stools passed weekly 22 or more stools passed weekly Takes laxatives, bran, ftoer Mucus In stools 3 stools daily often Straining at stool often Loose/watery stools often Hard stools often Feeling of Incomplete evacuation often Urgency often Blood In stools or toilet bowl
6.1 7.1 0.3 04 6.2 7.5 1.5 2.7 8.2 9.7 9.4 11.4 9.5 6.4
44.7 52.2 2.1 3.2 45.3 54.7 11.3 20.0 60.0 70.6 68.4 83.6 68.9 47.1
65.5 34.2 33.3 50.0 37.7 34.3 47.2 51.9 41.8 37.7 352 31.5 42 3 43.0
463.9 252.2 225.6 384.2 276.5 261.2 367.3 373.3 303.2 276.5 259.3 232.8 318.1 303.2
2.6 0.8 9.2 3.1 6.9 2.7 5.3 1.8 3.4
19.4 5.5 67.5 22.8 50.2 196 385 13.2 24.5
59.5 73.3 33.1 39.5 38.1 47.8 52.0 85.0 71.4
426.5 581.6 243.5 298.8 282.7 331.1 395.3 607.6 529.4
Symptom
Other gastrointestinal symptoms Nausea once a month or more Vomiting once a month or more Bloating (vlstole distension) often Difficulty swallowing often Heartburn once a month or more Heartburn several tmes a week or dally Acid regurgttabon once a month or more Weight loss a7 pounds Loss of appetite
Cumulative rate (%)
Rate per 1,000 person-years
• Often, >25% of the time.
disappearance rate (per 1,000 person-years) was 353. Of those with frequent gastroesophageal reflux symptoms on the first survey, 51 percent also reported frequent dyspepsia. Response bias
Based on data from the first survey, the responders and nonresponders to the second survey were analyzed to determine whether there were any question items that predicted
nonresponse to the second survey. In the logistic regression analysis, the variables age and sex were included at the first step. Although several individual questions were significant univariately, a joint simultaneous test for all candidate variables based on the residual chi-square test was not significant (p>0.15). Seven variables were identified a priori as potential factors that might have been associated with nonresponse to the second sur-
172
Talleyetal. Chronic constipalion Chronic diarrhea Frequent dyspepsia IBS (Manning criteria) Frequent abdominai pain
100 90
I
80
o.
70
8
60
o
50 40 30
,
400
CD C O O
360
C CO
—
— —
Chronic constipation Chronic diarrhea Frequent dyspepsia IBS (Manning criteria) Frequent abdominal pain
320 CO Q. CD 280 Q. Q. CO 240 CO 200
40-49
50-59
60-64
Age group, yr FIGURE 2. Disappearance rate per 1,000 person-years by age for chronic constipation, chronic diarrhea, frequent dyspepsia, the irritable bowel syndrome (IBS, £2 Manning criteria), and frequent abdominal pain: Olmsted County, Minnesota, 1988-1991.
vey. Three of these variables retained significance when analyzed multivariately: age, complainer score, and marital status. In particular, the 145 nonresponders were younger (median, 44 vs. 48 years), more likely to be classified as a "complainer" (i.e., those who tended to have multiple nongastrointestinal somatic symptoms, 57 percent vs. 48 percent), and unmarried (24 percent vs. 14 percent) in comparison with the responders. To determine the influence of these vari-
ables on the onset rates, the rates per 1,000 person-years for each of the symptom categories described previously were estimated separately by stratifying for each of the variables (table 4). The subjects who fell into the "complainer" category generally had a higher onset of gastrointestinal symptoms than did "noncomplainers." It should be noted that, since the odds of not responding were 1.4 times higher for "complainers" than "noncomplainers," the onset rates for
83.9 (62.3-105.6) 91.9 (35.5-146.8)
124.4* (87.9-160.9) 55.9 (34.0-77.9)
Married Yes No
Com plainer Yes No
* Significantly associated with developing the symptom (p < 0.05). f IBS, Irritable bowel syndrome. t Total person-years for the subjects at risk. § Numbers in parentheses, 95% confidence Interval.
67.8 (42.0-93.7) 101.5 (70.7-132.3)
95.9 (62.8-129.0) 76.8 (51.6-102.0)
708.6 84.7 (64.5-104.8)§
Frequent abdominal pain
Sex Male Female
Age 45 years or younger Over 45 years
Total person-yearstOverall
Variables associated with nonresponse
82.5*'(54.2-110.8) 54.1 (33.2-74.9)
69.2 (50.4-88.0) 52.8 (12.1-93.4)
60.4 (37.3-83.6) 72.9 (47.7-98.0)
85.2 (55.0-115.4) 54.3 (34.2-74.4)
795.3 66.6 (49.5-83.7)
IBSf (Manning criteria a2 symptoms)
52.4(29.7-75.1) 30.2(14.1-46.3)
41.4 (26.5-56.3) 35.0 (1.5-68.5)
40.1 (21.0-59.3) 40.6 (21.3-59.9)
50.3* (29.6-71.1) 10.6 (1.4-19.8)
25.0 (13.9-36.0) 55.9* (16.1-95.6)
36.5 (19.1-53.9) 22.2 (8.7-35.8)
32.7 (14.6-50.8) 26.8 (13.0-40.6)
888.4 29.3 (18.2-40.3)
792.7 40.4 (26.8-54.0) 53.6(29.0-78.1) 31.6(15.9-47.2)
Chronic diarrhea
Chronic constipation
Symptom categories (onset/1,000 person-years)
80.4''(52.8-108.1) 36.2 (18.9-53.5)
52.6 (36.0-69.1) 78.0 (29.9-126.2)
44.0 (23.7-64.3) 67.3 (43.5-91.0)
62.6 (37.0-88.3) 51.4 (31.6-71.2)
802.3 56.1 (40.3-71.8)
Frequent dyspepsia
TABLE 4. Onset/1,000 person-years of the main symptom categories stratified by variables associated with nonresponse In Olmsted County, Minnesota, residents, 1988-1991
en
I
227.6 (148.1-307.1) 300.6 (230.4-370.8)
193.4 (122.4-264.4) 337.5* (262.6-412.3)
270.0 (212.7-327.3) 272.4 (131.7-413.2)
278.1 (214.3-341.8) 252.8 (157.4-348.1)
Age 45 years or younger Over 45 years
Sex Male Female
Married Yes No
Com plainer Yes No
• Significantly associated with the disappearance of the symptom (p < 0.05). t IBS, irritable bowel syndrome. i Total person-years for the subjects at risk. § Numbers In parentheses, 95% confidence Interval.
297.0 (217.6-376.4) 233.5 (106.8-360.1)
257.5 (186.7-328.2) 441.7 (241.3-642.0)
199.2 (106.4-292.1) 345.5*1 (252.8-438.3)
279.3(195.3-363.2) 363.6 (249.6-477.7)
304.7 (232.0-377.3) 340.1 (140.4-539.8)
359.6 (255.7-463.5) 270.7(181.8-359.7)
322.6 (222.7-422.5) 296.3 (202.7-389.8)
148.9 308.9 (240.6-377.2)
146.3 280.3 (212.7-347.8)
233.1 270.3 (217.3-323.4)§
Total person-years}: Overall 250.8 (155.8-345.9) 308.6 (213.7-403.5)
Chronic constipation
IBSf (Manning criteria a2 symptoms)
286.4(160.9-412.0) 266.0 (20.2-511.7)
235.9(121.2-350.3) 611.8(343.7-879.9)
209.1 (55.1-363.1) 341.7(185.3-498.1)
354.6 (270.4-438.8) 344.6 (212.7-476.4)
358.1 (282.4-433.7) 303.9 (100.4-507.3)
261.5 (169.2-353.9) 461.3*1 (361.2-561.4)
337.3 (222.0-453.4) 360.3 (270.6-450.0)
139.4 351.7 (280.7^*22.6)
53.2 282.1 (170.1-394.1) 274.8(101.0-448.7) 287.1 (140.8-433.5)
Frequent dyspepsia
Chronic diarrhea
Symptom categories (onset/1 • 0 0 ° person-years)
Frequent abdominal pain
Variables associated with nonresponse
TABLE 5. Disappearance per 1,000 person-years oi the main symptom categories stratified by variables associated with nonresponse In Olmsted County, Minnesota, residents, 1988-1991
CD
CT •
