Prevalence and Socioeconomic Impact of Upper Gastrointestinal

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2005;3:543–552

ORIGINAL ARTICLES Prevalence and Socioeconomic Impact of Upper Gastrointestinal Disorders in the United States: Results of the US Upper Gastrointestinal Study MICHAEL CAMILLERI,* DOMINIQUE DUBOIS,‡ BERNARD COULIE,‡ MICHAEL JONES,§ PETER J. KAHRILAS,储 ANNE M. RENTZ,¶ AMNON SONNENBERG,# VINCENZO STANGHELLINI,** WALTER F. STEWART,‡‡ JAN TACK,§§ NICHOLAS J. TALLEY,* WILLIAM WHITEHEAD,储储 and DENNIS A. REVICKI¶ *Mayo Clinic College of Medicine, Center for Enteric Neurosciences and Translational Epidemiological Research, Rochester, Minnesota; ‡ Janssen Research Foundation, Beerse, Belgium; §Janssen Research Foundation, Titusville, New Jersey; 储Division of Gastroenterology and Hepatology, Northwestern University Medical School, Chicago, Illinois; ¶The MEDTAP Institute at UBC, Center for Health Outcomes Research, Bethesda, Maryland; #Division of Gastroenterology, Oregon Health & Science University, Portland, Oregon; **Department of Internal Medicine and Gastroenterology, University of Bologna, Bologna, Italy; ‡‡Geisinger Health System, Center for Health Research & Rural Advocacy, Danville, Pennsylvania; §§Department of Gastroenterology, University of Leuven, Leuven, Belgium; and 储储University of North Carolina at Chapel Hill, Center for Functional GI & Motility Disorders, Chapel Hill, North Carolina

Background & Aims: This study examined the prevalence of upper gastrointestinal (GI) symptoms and symptom groupings and determined impact on disability days in a nationally representative US sample. Methods: A telephone survey of 21,128 adults was conducted including questions about the presence of upper GI symptoms during the past 3 months. Respondents were categorized as symptomatic (ie, reported GI symptoms once per month) or asymptomatic. The survey included questions about missed work, leisure activity, or household activity days. Symptom groupings were identified by using factor analysis, and cluster analysis was used to assign respondents into distinct groups on the basis of these symptom groupings. Results: The prevalence of an average of 1 or more upper GI symptoms during the past 3 months was 44.9%. The most common symptoms experienced during the past 3 months were early satiety, heartburn, and postprandial fullness. Factor analysis identified 4 symptom groupings: (1) heartburn/ regurgitation; (2) nausea/vomiting; (3) bloating/abdominal pain; and (4) early satiety/loss of appetite. Five respondent clusters were identified; the largest clusters were primarily early satiety/fullness (44%) and gastroesophageal reflux disease–like symptoms (28%). Two small clusters reflected nausea and vomiting (7%) and a heterogeneous symptom profile (4%). Symptomatic respondents reported significantly more missed work, leisure, and household activity days than asymptomatic respondents (all P < .0001). Conclusions: Factor analysis separated GI symptoms into groupings reflecting gastroesophageal reflux disease and dyspepsia: early satiety, postprandial fullness, and loss of appetite; bloating and abdominal pain/discomfort; and nausea and

vomiting. These upper GI symptoms were associated with significant loss of work and activity days.

astrointestinal (GI) complaints comprise a broad array of symptoms that occur frequently in the general population, and often people report concomitant occurrence of multiple GI symptoms. Epidemiologic studies estimate the prevalence of at least one GI symptom in the past 3 months at 51%– 69% of the US population,1,2 and 91% report at least one symptom in the past year.3 Upper GI symptoms are a frequent complaint in primary care practice and are associated with significant health care utilization and impairment in health-related quality of life.1,2,4 –9 Among these symptoms, dyspepsia features prominently and has been defined as persistent or recurrent abdominal pain or discomfort characterized by postprandial fullness, early satiety, and nausea.10 Previous studies have found prevalences of 21%– 44% for heartburn symptoms,11–13 15% for reflux symptoms,14 14%–20% for gastroesophageal reflux disease (GERD),2,12,14 –16 3.4% for nonulcer dyspepsia symptoms,17 and 15%–30% for dyspepsia.3,18 –24 These symptoms are associated with increased reports of restricted activity and missed work days.4 Although the

G

Abbreviations used in this paper: GERD, gastroesophageal reflux disease; GI, gastrointestinal; NHIS, National Health Interview Survey. © 2005 by the American Gastroenterological Association 1542-3565/05/$30.00 PII: 10.1053/S1542-3565(05)00153-9

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epidemiology of these symptoms is well described, prior epidemiologic studies were often limited in scope of the design, survey methods, and representativeness of the sample. Few US nationally representative samples have been studied,1 and often symptom survey questions were not comprehensive. The consensus of experienced clinicians has been used to define distinct subgroups of functional GI disorders,25 in part because of the absence of large population-based epidemiologic studies of GI symptoms.3,26 Other researchers have used factor analysis to validate symptom criteria. The rationale for this method is that, if GI symptoms consistently group together in multiple independent samples, it is reasonable to infer that these symptoms share a common etiology. These empirically derived groups of symptoms can then be compared with symptoms identified by consensus criteria to evaluate the convergent validity of the consensus criteria.26 Exploratory factor analysis, if confirmed with other independent samples, can also identify other clinically useful groupings of GI symptoms. Care must be exercised in this approach, because the findings of factor analyses are dependent on the GI symptoms measured, the study sample, and the methods used to generate the factor solution. To better understand the prevalence and diversity of expression of upper GI symptoms and to determine the impact of these symptoms in the general US population, we conducted a nationwide telephone interview survey involving more than 20,000 respondents. The objective of this study was to determine the prevalence of upper GI symptoms in the US population and to identify distinct subgroups of individuals with different combinations of functional GI symptoms based on factor analysis and cluster analysis. In this context, cluster analysis provides an empirical method for identifying clusters of subjects with naturally co-occurring GI symptoms and extends the findings of the factor analyses.

Methods Design and Sample A US national telephone survey was conducted to estimate variation in prevalence and impact of upper GI symptoms in the general population. A US nationwide random sample of telephone numbers was obtained to conduct a survey of English speaking adults 18 years and older. Before initiating the survey, telephone numbers were assigned an 8-digit random number, sorted by random number, and called in order as sorted. A quota method27,28 was used to yield a sample representative of the continental US population within 24 strata defined by the combination of gender, age groups (18 – 44,

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 3, No. 6

45– 64, ⱖ65 years), and region of the country (Northeast, Midwest, South, and West). Ten attempts were made to contact each household. One adult was interviewed per household, and if there were multiple eligible adults in a household, the respondent was selected on the basis of the birth date closest to the date of the interview.27,28 If the person selected was not available at the time of initial contact, arrangements were made to call back at a more convenient time. If the selected individual refused, no substitution was permitted. When the quota for defined gender-region-age strata was met, subsequent identified individuals who met the profile of those strata were ineligible to participate in the study. The Essex Institutional Review Board approved the study protocol and the informed consent statement. For all interviews, respondents gave informed verbal consent before initiating data collection. To estimate the required sample size, we projected the lowest prevalence GI condition from the literature, gastroparesis estimated at 2.4%, determining that 12% of study participants would self-report diabetes, and 20% of those would meet the case definition for gastroparesis.

Survey Instrument Development A computer-assisted telephone interview was developed and evaluated for respondent understanding, comprehension, and reliability. The computer-assisted telephone interview was developed after an extensive review of the medical literature and other GI surveys.1,12,29 –33 Gastroenterologists and epidemiologists were consulted to ensure that the selected symptom-related items were comprehensive and covered key features of GI symptoms and disorders. Cognitive interviewing techniques were used to confirm individual understanding of the questions, and a test-retest reliability study was completed before fielding the national survey. The interview included questions about demographic characteristics (ie, age, gender, education, marital status, and work status), pregnancy status, smoking status, use of medications, and acute gastrointestinal illnesses during the past 3 months. A series of 12 screening questions were asked about the presence of upper GI symptoms (ie, heartburn, regurgitation [2 questions], dysphagia, postprandial fullness, early satiety [2 questions], nausea, vomiting, troublesome or excessive belching, bloating, and abdominal pain or discomfort) during the past 3 months. Positive responses to any one (or more) of the screening questions were followed by a series of more detailed symptom-specific questions on frequency, intensity, duration, and location. Questions about abdominal pain and discomfort were followed by a series of questions designed to determine whether the sensation reported was pain or discomfort. Follow-up symptom-related questions were not asked of those who responded “No” to a specific screening question because it would result in respondents being asked logically inconsistent questions. Three questions were asked about lost work, lost leisure activity, and lost household activity days during the past 3 months.34 The specific questions on disability days were (1)

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On how many days in the last 3 months did you miss work because of illnesses?, (2) On how many days in the last 3 months did you miss family, social, or leisure activities because of illnesses?, and (3) On how many days in the last 3 months did you not do household work because of illnesses? Test-retest reliability of individual GI symptom screening and symptom-related questions was assessed in a general population sample of 389 adults. There was a median of 15 days between the 2 interviews. The kappa statistics were greater than 0.50 for most screening questions, and agreement was consistently higher when reliability analyses were restricted to individuals who reported greater symptom intensity. On the basis of the pilot survey, screening questions about nausea and vomiting were modified to improve respondent comprehension and understanding.

Data Analysis Analysis focused on the following upper GI symptoms: heartburn, regurgitation, postprandial fullness, troublesome belching, early satiety, upper abdominal pain or discomfort, bloating, nausea, and vomiting. Overall prevalence of the different GI symptoms was reported for those respondents reporting the specific symptom greater than or equal to once per month. On the basis of the expert consensus recommendations of a gastroenterologist advisory panel, clinically relevant symptom frequency was ⱖ2 times per week for heartburn, regurgitation, early satiety, and postprandial fullness; ⱖ1 time per week for nausea, vomiting, bloating, and abdominal pain or discomfort; and ⬎1 time per month for dysphagia. With these threshold criteria, prevalence estimates were derived for these symptoms. Respondents were defined as symptomatic if they reported experiencing symptoms equal to or greater than once per month for the prior 3 months; otherwise they were defined as asymptomatic. Defining a lower bound criterion helped avoid the problem of false-positive classification as a case when incidental occurrence of a symptom was recorded. For most symptoms, a frequency of less than once per month was deemed to be too infrequent to be meaningful. Leisure and household activity lost days were compared between asymptomatic and symptomatic respondents by using t tests for independent groups. The comparisons of work loss days were restricted to respondents who worked full-time or part-time. Two-tailed P values of .0001 were used to assess statistical significance, given the large sample size. The analyses focusing on identifying naturally occurring symptom groupings were restricted to those respondents who reported the presence of at least one of the screening upper GI symptoms (45% of the total sample). This decision was made on the basis of the consideration that respondents reporting no symptoms could not meaningfully contribute to the data analyses. The data analysis proceeded in 3 steps: (1) identify symptom groupings on the basis of factor analysis; (2) cluster analysis of respondents on the basis of the identified factors (ie, symptom groupings) determined in the factor analysis; and (3) description of clusters on the basis of the symptom content.

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A factor analysis35,36 with orthogonal rotation was completed by using the presence/absence or dichotomized responses to selected GI symptom items. The number of factors was determined on the basis of eigenvalues (ie, ⬎1.0), the scree test, and assessments of simple structure.35,36 We used factor loading of greater than 0.40 to interpret each derived factor. We performed oblique rotations (not shown), with no substantive changes in factor number, structure, or interpretation; therefore we only report the results of the orthogonal rotations. On the basis of these factors (ie, symptom groupings), nonhierarchical cluster analysis37 was completed. The selection of the final cluster solution was based on the internal homogeneity criterion. In cases in which multiple solutions differed only marginally on this criterion, preference was given to simpler solutions and the solution that appeared to subgroup otherwise large clusters. When a very large cluster was identified in addition to several smaller clusters, further analyses were completed to determine whether the large cluster could be divided into several distinct subclusters. Only clusters representing greater than 3.0% of the total sample (about 284 individuals) are reported.

Results Respondents All 24 gender-region-age strata were reached, and a total of 21,128 interviews were completed between April and September 1999. A total of 65,860 households were contacted, with 24,734 defined as ineligible. The 2 most common reasons for ineligibility were incompatible schedule (n ⫽ 14,812) and language barrier (n ⫽ 4516). From eligible households, 73.7% agreed to participate in the survey (ie, gave a complete or partial interview). Of those who participated, 12.6% gave a partial interview. The analytical sample was 17,484, with 3644 respondents removed from the analyses because of study exclusion criteria. Respondents were excluded if they reported known causes for their GI symptoms (eg, pregnancy, stomach flu, peptic ulcer, Crohn’s disease, ulcerative colitis, or GI cancers). The most frequent reasons for exclusion were flu (44.2%), ulcers (32.6%), and pregnancy (11.9%). Table 1 summarizes the demographic characteristics of the total sample, symptomatic, and asymptomatic respondents and compares them to the US population. The average age was 46.0 years (standard deviation, 17.6), and 18.0% were 65 years or older. Fifty-four percent were female, 56% attained a college or advanced graduate degree, and 55% worked full-time or part-time. The total sample was comparable to the US population, except for racial group and education level. The symptomatic and asymptomatic groups were comparable in demographic characteristics.

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Table 1. Demographic Characteristics

N % Female % Married Race White Black Hispanic Native American Asian Other Education ⱕ High school Technical degree College Graduate school % Employed full-time or part-time Health insurance Private Government programsb Uninsured

Total samplea

Symptomatic

Asymptomatic

US population

21,128 54.1% 55.3%

9480 53.9% 53.1%

8004 49.6% 57.4%

— 51.8% —

82.4% 8.6% 3.9% 0.7% 1.1% 3.3%

81.3% 9.4% 4.6% 0.7% 1.0% 3.0%

82.8% 8.2% 3.2% 0.6% 1.5% 3.7%

72.1% 12.1% 11.4% — 3.7% 0.7%

41.3% 2.8% 45.2% 10.7% 55.3%

42.5% 2.5% 45.5% 9.6% 57.5%

40.1% 2.9% 44.5% 12.5% 54.3%

51.4% 7.1% 34.5% 7.0% —

63.9% 22.0% 14.1%

64.9% 20.3% 14.9%

63.5% 22.9% 13.6%

— — —

symptomatic (those reporting symptoms ⱖ1 time/mo for the past 3 mo), asymptomatic (those reporting symptoms ⬍1 time/m for the past 3 mo), and ineligible respondents (respondents were excluded if they reported known causes for their GI symptoms; pregnancy, stomach flu, peptic ulcer, Crohn’s disease, ulcerative colitis, or GI cancers). bIncludes Medicare, Medicaid, other public aid programs, Civilian Health and Medical Program of Uniformed Services, or other military programs. aIncludes

Symptom Profile Of the total sample of respondents, 44.9% experienced an average of 1 or more GI symptoms each month during the past 3 months. Eighty-two percent of respondents reported at least 1 of the GI symptoms

during the past 3 months. The most commonly reported upper GI symptoms were heartburn, postprandial fullness, feeling full soon after starting to eat, and regurgitation (Table 2). The least commonly experienced symptoms include abdominal pain and/or discomfort and

Table 2. Prevalence of Upper Gastrointestinal Symptoms % With clinically relevant upper GI symptomsb

% With ⱖ1 ⫻ montha

Heartburn Regurgitation Dysphagia Bloating Postprandial fullness Early satiety Nausea Vomiting Belching/burping Abdominal painc Abdominal discomfortc Bothc Abdominal pain/discomfort (above navel)d

Total (N ⫽ 17,484)

Male (N ⫽ 8408)

Female (N ⫽ 9076)

Total (N ⫽ 17,484)

Male (N ⫽ 8408)

Female (N ⫽ 9076)

21.6% (3,768) 16.4% (2,861) 7.8% (1,372) 10.7% (1,869) 20.9% (3,658) 23.0% (4,028) 9.5% (1,655) 2.7% (479) 6.3% (1,096) 0.8% (143) 4.3% (747) 4.8% (846) —

21.9% (1,844) 16.9% (1,421) 7.6% (639) 8.3% (699) 19.6% (1,647) 20.1% (1,687) 6.8% (573) 2.1% (173) 5.4% (454) 0.7% (58) 4.3% (363) 3.8% (319) —

21.2% (1,924) 15.9% (1,440) 8.1% (733) 12.9% (1,170) 22.2% (2,011) 25.8% (2,341) 11.9% (1,082) 3.4% (306) 7.1% (642) 0.9% (85) 4.2% (384) 5.8% (527) —

6.3% (1,105) 2.9% (502) 4.6% (801) 4.5% (794) 3.6% (625) 5.3% (924) 2.2% (393) 0.4% (71) 3.0% (521) — — — 2.3% (409)

2.8% (483) 1.3% (225) 2.1% (372) 1.7% (289) 1.5% (261) 1.8% (315) 0.7% (122) 0.2% (30) 1.2% (212) — — — 1.0% (176)

3.6% (622) 1.6% (277) 2.5% (429) 2.9% (505) 2.1% (364) 3.5% (609) 1.5% (271) 0.2% (41) 1.8% (309) — — — 1.3% (233)

included symptomatic respondents, those reporting the specific symptom ⱖ1 time/mo for the past 3 months. included respondents reporting clinically relevant upper GI symptoms for the past 3 months. The definition of clinically relevant upper GI symptoms was based on the expert consensus recommendations of a gastroenterologist advisory panel. These definitions included reporting of, ⱖ2 times/wk for heartburn, regurgitation, early satiety and postprandial fullness; ⱖ1 time/wk for nausea, vomiting, bloating and abdominal pain, or discomfort above the navel; and ⬎1 time/mo for dysphagia. cPrevalence using the screening question was not location specific. dDetermination of clinically relevant abdominal pain/discomfort was restricted to above the navel or an upper GI location. aAnalysis bAnalysis

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Table 3. Co-occurrence of Upper GI Symptoms (N ⫽ 17,484)a Symptom

N

Regurgitation

Dysphagia

Bloating

Heartburn Regurgitation Dysphagia Bloating Postprandial fullness Early satiety Nausea Vomiting Belching Abdominal pain/discomfort

3768 2861 1372 1869

1653 (43.9)

664 (17.6) 664 (23.2)

881 (23.4) 790 (27.6) 403 (29.4)

aAnalysis

Postprandial fullness

Early satiety

Nausea

1274 (33.8) 1111 (38.8) 610 (44.5) 933 (49.9)

1339 (35.5) 1198 (41.9) 666 (48.5) 887 (47.5)

719 (19.1) 700 (24.5) 347 (25.3) 498 (26.6)

1704 (46.6)

693 (18.9) 929 (23.1)

3658 4028 1655 479 1096

Belching

Abdominal pain/discomfort

215 (5.7) 246 (8.6) 130 (9.5) 152 (8.1)

654 (17.4) 615 (21.5) 257 (18.7) 470 (25.1)

864 (22.9) 780 (27.3) 373 (27.2) 689 (36.9)

223 (6.1) 290 (7.2) 479 (28.9)

498 (13.6) 510 (12.7) 334 (20.2) 121 (25.3)

720 (19.7) 861 (21.4) 598 (36.1) 190 (39.7) 398 (36.3)

Vomiting

1746

included symptomatic respondents (those reporting the specific symptom ⱖ1 time/mo for the past 3 months).

vomiting. Gender differences were observed for early satiety (female: 25.8% vs male: 20.1%) and nausea (female: 11.9% vs male: 6.8%). The most prevalent clinically relevant upper GI symptoms were heartburn (6.3%) and early satiety (5.3%) (Table 2). Clinically relevant symptoms with the lowest prevalence were vomiting (0.4%), nausea (2.2%), and abdominal pain/discomfort above the navel (2.3%). Twice as many women as men experienced early satiety and nausea as clinically relevant symptoms. Association Between Symptoms The association between pairs of upper GI symptoms was examined in symptomatic respondents. Cooccurrence proportions ranged from less than 6% (heartburn and vomiting) to 49.9% (bloating and postprandial fullness) (Table 3). High co-occurrence proportions were observed for dysphagia and early satiety (48.5%), bloating and early satiety (47.5%), early satiety and postprandial fullness (46.6%), dysphagia and postprandial fullness (44.5%), and heartburn and regurgitation (43.9%).

Factor and Cluster Analysis The factor analysis, with orthogonal rotation, resulted in 4 interpretable factors (Table 4). The first factor was interpreted as related to GERD, because the symptoms with the strongest loadings were regurgitation and heartburn. The second factor was identified as nausea and vomiting. The third factor included significant loadings for symptoms of bloating, abdominal pain/discomfort, belching, and fullness after eating. The fourth factor was identified as early satiety, given the significant loadings of symptoms related to that symptom construct, feeling full soon after starting to eat, and loss of appetite. The belching item loaded on both the bloating/abdominal pain or discomfort factor (0.50) and the heartburn/regurgitation factor (0.31). The fullness item also loaded on the bloating factor (0.49) and the early satiety factor (0.31). The derived cluster structure is summarized in Figure 1, and symptom prevalence for each cluster is summarized in Table 5. Cluster 1 (bloating), representing 17% of the sample, was dominated by the

Table 4. Factor Analysis of Upper Gastrointestinal Symptomsa Symptom

Heartburn/regurgitation

Bitter/acid/sour taste–mouth/throat Fluid/food return to throat/mouth Heartburn/burning sensation Food stuck in chest when swallowing Nausea Vomit/heave/retch Bloating Pain/discomfort in abdomen Belch/burp bothersome Excessive fullness after eating Felt full soon after starting to eat Lost your appetite

0.7665 0.7146 0.5697 0.3901

aAnalysis

Nausea/vomiting

Bloating/abdominal pain or discomfort

Early satiety/loss of appetite

0.8343 0.8303

0.3110

0.7596 0.5330 0.5039 0.4858


0.3104 0.7604 0.6710

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Figure 1. Results of cluster analysis of gastrointestinal symptoms.

satiety and also included relatively high rates of reflux, dysphagia, fullness, loss of appetite, bothersome belching, and abdominal pain/discomfort.

sensation of bloating, but postprandial fullness, abdominal pain/discomfort, and heartburn were also present in one third to one half of all members. Cluster 2 (nausea; 7%) reflected nausea and vomiting, with all respondents reporting nausea and almost half reporting vomiting; approximately one quarter of all members also reported heartburn and abdominal pain/discomfort. The most distinguishing symptoms of the largest cluster (44% of respondents), Cluster 3 (fullness), were fullness and early satiety followed by loss of appetite. Cluster 4 (GERD), which was the second largest cluster (28%), was composed of GERD-related symptoms of heartburn, reflux, and bitter/sour/acid taste in the mouth. Cluster 5 (undefined), which was the smallest cluster (4%), was also the most heterogeneous and suggests a segment of the patient population with broad-ranging upper GI symptomatology. It included high rates of nausea, bitter/sour/acid taste in the mouth, and early

Missed Days as a Result of Illness Table 6 summarizes, by upper GI symptom, the average number of missed work days during the past 3 months for symptomatic compared with asymptomatic respondents who reported being employed. Results show that symptomatic employed respondents missed more work days than asymptomatic employed respondents (all P ⬍ .0001). Vomiting was associated with the most missed work days during the prior 3 months. Only postprandial fullness was responsible for less than 1 missed work day during the prior 3 months. Respondents reporting upper GI symptoms missed on average more leisure activity and household activity days than the asymptomatic group (Table 6; all P ⬍ .0001). For each GI symptom, symptomatic respondents missed

Table 5. Cluster Analysis: Upper Gastrointestinal Symptom Profile (N ⫽ 9480)a Cluster 1

2

3

4

5

Symptom

Bloating (N ⫽ 1644, 17%)

Nausea (N ⫽ 671, 7%)

Fullness (N ⫽ 4143, 44%)

GERD (N ⫽ 2665, 28%)

Undefined (N ⫽ 357, 4%)

Heartburn/burning sensation Fluid/food return to throat/mouth Bitter/acid/sour taste–mouth/throat Food stuck in chest when swallowing Excessive fullness after eating Felt full soon after starting to eat Loss of appetite Nausea Vomiting Bothersome belching/burping Bloating Pain/discomfort in abdomen

32 8 20 10 46 18 7 13 0 30 71 47

27 8 15 8 17 15 27 100 48 6 7 22

17 2 9 13 54 51 34 7 0 2 6 6

78 30 52 16 11 9 6 5 0 11 6 11

76 75 83 55 72 79 73 92 45 58 68 76

aAnalysis


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Table 6. Missed Work, Leisure, and Household Activity Days by Upper Gastrointestinal Symptoma

Symptom

Nb

Missed work days, mean (SD)

Asymptomatic Heartburn Regurgitation Dysphagia Postprandial fullness Early satiety Nausea Vomiting Belching Bloating Abdominal pain/discomfort (above navel)

4323 1632 965 416 1078 1498 522 99 430 786 443

0.4 (3.2) 1.0 (6.0) 1.3 (7.2) 1.3 (5.4) 0.9 (5.0) 1.1 (5.0) 2.2 (8.9) 4.4 (13.2) 1.4 (7.4) 1.4 (7.3) 1.9 (9.0)

Nc

Missed leisure days, mean (SD)

Nc

Missed household days, mean (SD)

7932 2764 1736 783 1754 2473 883 180 779 1406 710

0.3 (3.3) 1.2 (7.4) 2.0 (10.4) 2.4 (11.1) 1.4 (8.4) 1.6 (9.3) 3.3 (12.9) 5.7 (17.3) 2.0 (9.9) 1.8 (9.4) 2.7 (11.8)

7893 2730 1711 776 1735 2456 860 171 765 1378 694

0.5 (4.8) 2.4 (11) 3.5 (13.5) 4.7 (15.5) 3.1 (12.4) 3.2 (12.8) 6.6 (18.2) 13.1 (25.5) 4.3 (14.1) 4.2 (14.9) 4.6 (15.2)

SD, standard deviation. t test between symptomatic and asymptomatic subjects. All P values significant at ⬍.0001. Symptomatic respondents are those reporting the specific symptom ⱖ1 time/mo for the past 3 months. Asymptomatic respondents are those reporting symptoms ⬍1 time/mo for the past 3 months. bAnalysis included symptomatic and asymptomatic respondents who reported working for pay at least part-time. cAnalysis included all symptomatic and asymptomatic respondents. aStudent

more household activity days than leisure activity days. Missed leisure activity days ranged from a mean of 1.2 (heartburn) to 5.7 (vomiting) days. During the previous 3 months, symptomatic respondents reported missing household activity ranging from an average of 2.4 (heartburn) to 13.1 (vomiting) days. As with missed work days, vomiting was associated with the most missed leisure activity and household activity days.

Discussion The US Upper Gastrointestinal Study is the largest general population survey of upper GI symptoms conducted in North America. The study sample is unique because it includes a mix of respondents, representative of the US noninstitutionalized population who might or might not have accessed health care services for their GI symptoms. The most common upper GI symptoms reported in the general population were early satiety, defined as loss of appetite or feeling full soon after starting to eat, heartburn, and postprandial fullness. For most symptoms, women reported proportionately more symptom experience than men. The exception was that men reported more heartburn and regurgitation and slightly more abdominal discomfort than women. We conducted factor analyses followed by cluster analyses of respondents who reported at least 1 GI symptom during the previous 3 months (45% of total sample). The results of the factor analysis demonstrate the grouping of different GI symptoms based on the covariation between these symptoms. On the basis of these factor analysis results, cluster analyses can be used to group respondents

on the basis of their symptom reporting to identify consistent and observed groupings of GI symptoms. The factor analysis indicated 4 interpretable factors identified as heartburn/regurgitation, nausea/vomiting, abdominal pain/discomfort and bloating, and early satiety/fullness. In general, our results are consistent with previous factor analyses of GI symptoms.2,3,26,38,39 However, it is difficult to compare results of factor analyses across different studies primarily because of differences in the survey questions used to collect data on GI symptoms, sample characteristics, and factor analysis methods. Our study focused on upper GI symptoms, which were asked of all respondents, and did not focus on lower GI symptoms. This study also explored whether there were clustering of these symptom factors in the symptomatic general population. The results of the cluster analyses demonstrate that many respondents from the general population experience several different combinations of upper GI symptoms. Most respondents report symptoms consistent with a predominant symptom: fullness (cluster 3, 54%), heartburn (cluster 4, 78%), nausea (cluster 2, 100%), or bloating (cluster 1, 71%). However, 4% of respondents reported combinations of different gastrointestinal symptoms (cluster 5, undefined). The mix of gastrointestinal symptoms represented in this undefined cluster included heartburn/regurgitation, functional dyspepsia-related symptoms, and nausea. Patients often have overlapping dyspepsia and GERDrelated symptoms.23,32,40 – 42 This overlap might have important diagnostic and therapeutic implications. However, there is no consensus on the pathophysiologic

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basis for the functional GI disorders; therefore they are diagnosed on the basis of the presence and absence of specific symptoms.25 The findings are generally consistent with symptoms associated with consensus-based GI disorders. The key symptoms associated with diagnosis of GERD (ie, regurgitation and heartburn) grouped together in the factor analysis and are very consistent with clinical evidence.14,32,43 The cluster analysis in our study demonstrated that one cluster, incorporating 28% of symptomatic respondents, reported symptoms consistent with GERD alone, and another 4% (cluster 5) reported symptoms of heartburn/regurgitation and other upper GI symptoms. Several groupings of upper GI symptoms were identified in this study and are characterized by abdominal pain or discomfort and bloating, early satiety, postprandial fullness and loss of appetite, and nausea and vomiting. The analyses found factors that are consistent with current insights on the pathophysiology of functional dyspepsia, including visceral hyperalgesia (epigastric pain), impaired postprandial fundic accommodation (early satiety, postprandial fullness), and delayed gastric emptying (postprandial fullness).42,44 – 48 However, the close association between pathophysiology and functional dyspepsia symptoms is uncertain, and there are conflicting published data. The factor and cluster analyses confirmed that postprandial fullness and early satiety are highly prevalent and distinct symptom groupings in the general population. The identification of these clusters has not yet been demonstrated to influence clinical decision making and practice and remains to be tested in formal prospective studies. Across all upper GI symptoms, symptomatic respondents reported significantly more missed days from work, social, or household activities than asymptomatic respondents. The societal burden of missed work was especially high among respondents reporting nausea, vomiting, and abdominal pain/discomfort symptoms. These findings are comparable to the disability day data from previous North American samples. Frank et al2 found that respondents with nausea or vomiting and abdominal pain were more likely to report lost work time than those with GERD-like symptoms or GERD plus nausea or vomiting. However, data from the National Health Interview Survey (NHIS) indicate that annual lost work and activity days per year might be lower than the results in our study.17,49 In the NHIS survey, respondents with GERD-like symptoms reported 4.4 restricted activity days and 0.6 lost work days per year compared to estimated annual rates of 4.8 – 8 restricted activity days and


4 –5.2 lost work days based on our survey. The NHIS also provided restricted activity and lost workday data for respondents with non-ulcer dyspepsia-type symptoms. These results also demonstrated fewer restricted activity days and lost workdays than reported in our survey. Respondents consistently reported lost workdays and limitations to leisure and household activities if they experienced dyspepsia-related symptoms or dyspepsiarelated symptoms combined with heartburn/regurgitation symptoms. These findings are not surprising because previous studies have found that the functional gastrointestinal disorders are associated with impairment in functioning, well-being, and work loss.1,2,5,7,8,21,26 Several limitations must be considered when interpreting the findings and generalizability of the study. First, the GI symptom data were collected directly from individuals by using telephone surveys, and there was no access to medical records or clinician-assigned diagnoses and/or tests. Although we evaluated the validity and reliability of the survey questions, it was not possible to examine criterion validity. Symptom data are based on self-report and might be subject to bias; however, this measurement approach has been used frequently in epidemiologic research. Second, this study was the largest epidemiologic survey of GI symptoms completed in the US and, therefore, is likely to be representative of the natural variation in GI symptoms in the community. Caution must be exercised in generalizing to nonwhite minorities because there were fewer minority respondents in the final sample. Third, the data are based on respondent recall of symptoms and disability days experienced during the past 3 months. Three-month recall has been used previously in other epidemiologic GI studies,50 and similar disability days questions have little recall bias.34 Fourth, the groupings of GI symptoms were identified by factor and cluster analyses, and these groupings are dependent on the sample, content of survey questions, and statistical methods. As compared to previous surveys, our questionnaire included more detailed questions on upper GI symptoms and fewer questions on lower GI symptoms. However, the consistency in these symptom-related factors across different studies makes it reasonable to infer existence of common upper GI symptom groupings. Finally, no measure of psychological comorbidity was included in the survey; therefore it is unknown whether the observed disability days might be attributable only to GI symptoms. In conclusion, we evaluated the prevalence and natural grouping and occurrence of upper GI symptoms from a large US general population survey. The results of this study can help physicians understand the natural group-

June 2005

ings of common GI symptoms in the general population. The findings might be more generalizable to the general community residing in US communities than other recent epidemiologic surveys that were based on householders or residents of Olmsted County, Minnesota.1–3,51 We found that there is evidence supporting groupings of symptoms consistent with heartburn/regurgitation, bloating/abdominal pain or discomfort, early satiety/fullness, and nausea/vomiting. Dyspepsia-related symptoms were differentiated into 3 groupings: (1) nausea and vomiting, (2) early satiety, postprandial fullness, and loss of appetite, and (3) bloating and abdominal pain/discomfort. The combined use of factor analysis and cluster analysis provided a useful method for identifying GI symptom groupings based on covariation in symptoms and co-occurrence of symptoms in respondents. This study provides information on naturally co-occurring clusters of symptoms and might be valuable in identifying potentially clinically important targets for clinical intervention and treatment. By identifying symptom clusters and understanding the underlying pathophysiology, it is anticipated that the approach of directing therapy to underlying mechanism can result in better patient outcomes. For example, Tack et al47 and Stanghellini9 have shown in large studies that postprandial fullness is associated with gastric emptying delay. This patient group might be more responsive to treatment with motility enhancing agents than the nonselective use of those treatments for patients with nonspecific dyspeptic symptoms. The study also demonstrated the significant socioeconomic impact of these common upper GI symptoms that occur in 45% of the general population.

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Address requests for reprints to: Dr Dennis Revicki, Center for Health Outcomes Research, The MEDTAP Institute at UBC, 7101 Wisconsin Avenue, Suite 600, Bethesda, Maryland 20814. e-mail: dennis.revicki@ unitedbiosource.com; fax: (301) 654-9864. Supported by Janssen Research Foundation, Titusville, NJ. Drs Coulie, Dubois, and Jones are employees of Johnson & Johnson. Dr Revicki and Ms Rentz are employees of MEDTAP International and have received research study support from Johnson & Johnson, Novartis, GlaxoSmithKline, and AstraZeneca. Dr Camilleri has served as a consultant to Johnson & Johnson within federal guidelines for nonsignificant financial conflict of interest based on annual income. He has also received research study support from Johnson & Johnson. Dr Kahrilas has received research study support from AstraZeneca, Medtronics, and Janssen Esai. Dr Whitehead has served as a consultant to Johnson & Johnson within federal guidelines for nonsignificant financial conflict of interest based on annual income. He has also received research study support from Johnson & Johnson, Solvay Pharmaceuticals, AstraZeneca, and Forest Labs. The authors thank Drs Patricia Robinson and Sheldon Sloan for their significant contributions to the development of the questionnaire interview.