The American Journal of Managed Care November 2011
US Prevalence of Upper Gastrointestinal Symptoms: A Systematic Literature Review
Objectives: To quantify the prevalence of dyspeptic and gastroesophageal symptoms and peptic ulcer disease (PUD) in the United States and to identify factors affecting their prevalence.
Study Design: Systematic search of MEDLINE and Web of Science through November 2010.
Methods: We identified studies of US patients and evaluated a general (not disease-specific) adult sample that reported the prevalence of 1 or more upper gastrointestinal (GI) outcomes of interest, including dyspeptic symptoms, gastroesophageal symptoms, dyspeptic and/or gastroesophageal symptoms, or PUD. Proportions of individuals in each study reporting each symptom were pooled to derive separate prevalence estimates. Qualitative synthesis of data depicting multivariate relationships between covariates and upper GI outcomes was undertaken.
Results: A total of 36 citations representing 24 studies were included: 9 studies reporting dyspeptic symptoms (n = 14,181), 14 reporting gastroesophageal symptoms (n = 58,701), 5 reporting dyspeptic and/or gastroesophageal symptoms (n = 103,175), and 7 reporting PUD prevalence (n = 269,299). The pooled prevalences of dyspeptic, gastroesophageal, and dyspeptic and/or gastroesophageal symptoms were 16.3% (95% confidence interval [CI] 9.1%-25.1%), 24.2% (95% CI 18.2%-30.5%), and 35.2% (95% CI 14.9%-58.9%). The pooled prevalence for studies asking for shorter-term PUD recall was 3.3% (95% CI 2.2%-4.6%), with lifetime PUD prevalence estimated at 13.8% (95% CI 10.7%-17.0%). The influence of covariates evaluated as part of multivariate analyses was often inconsistent.
Conclusions: It appears that upper GI symptoms and disorders are common in US inhabitants. We identified patient- and study-level factors that should be considered when assessing upper GI symptom prevalence and conducting future research.
(Am J Manag Care. 2011;17(11):e449-e458)
Systematic review and meta-analysis indicated that upper gastrointestinal symptoms and disorders are common to inhabitants of the United States.
- The pooled prevalences of dyspeptic, gastroesophageal, and dyspeptic and/or gastroesophageal symptoms were 16.3%, 24.2%, and 35.2%.
- In studies asking for shorter-term peptic ulcer disease (PUD) recall, the pooled prevalence was 3.3%; in studies asking for lifetime PUD recall, the prevalence was estimated at 13.8%.
- The influence of covariates on prevalence rates was often inconsistent.
Currently available studies suggest a high burden of disease due to upper GI symptoms.8-43 However, due to a lack of standardization of upper GI symptom definitions and differences in methodology used between studies, available prevalence estimates have varied greatly.1-4,8 Furthermore, data suggest that prevalence of upper GI symptoms can vary markedly between countries.42 The decision for managed care organizations to pay for medications depends on the prevalence of the condition in a population. When different studies report different values, it becomes difficult to estimate true population prevalence. Estimates provided by a systematic review and meta-analysis can be helpful in such situations. Despite this fact, no previous systematic review and meta-analysis focusing on US prevalence rates of upper GI symptoms have been undertaken. Finally, it has been proposed that associations between sociodemographic and other covariates can affect upper GI symptom prevalence9,41; however, no prior attempt has been made to gather and synthesize such data.
In order to gain a better understanding of the prevalence of dyspeptic and gastroesophageal symptoms and PUD in the US population, and to more completely identify factors that affect their prevalence, we sought to conduct a comprehensive and systematic review of the literature on this topic.
A systematic literature search using the MEDLINE (1950 through November 2010) and Web of Science (1994 through November 2010) computerized databases was conducted. The search combined keywords and medical subject headings (MeSH) terms related to upper gastrointestinal, dyspeptic, and gastroesophageal symptoms and PUD, along with “prevalence.” The complete search strategy is available in Appendix 1, available at www.ajmc.com. Additionally, the references of each pertinent article identified were reviewed to locate other relevant published works.
To be included in this systematic review, studies had to (1) be conducted in the United States (as clear differences in GI symptom prevalence exist between countries); (2) be published in English; (3) evaluate a general (not disease-specific) adult sample selected without prior knowledge or suspicion of the presence or absence of GI symptoms or disorders; and (4) report the prevalence of at least 1 upper GI outcome of interest, including dyspeptic symptoms (eg, postprandial fullness, early satiety, localized epigastric pain, diffuse epigastric pain, belching, nocturnal/fasting pain, abdominal distention), gastroesophageal symptoms (eg, heartburn, regurgitation), dyspeptic and/or gastroesophageal symptoms (at least 1 related dyspeptic or gastroesophageal symptom), or PUD (eg, gastric or duodenal ulcer). Database studies evaluating only the rate of healthcare utilization for upper GI symptoms or disease were not included. Only fully published manuscripts were considered. In studies with more than 1 published report on the same study population, the most recent publication was selected for analysis to avoid double-counting participants, although previous publications were reviewed to supplement for missing data where applicable. When studies with nonidentical but overlapping populations were identified, the most recent publication was again selected for analysis.
Upon determination of inclusion, studies were further assessed to see whether they reported on the relationship between any sociodemographic or other covariates and upper GI symptom prevalence. To be included in this second portion of the systematic review, studies had to have (1) conducted multivariate analysis and (2) reported the results of at least 1 relationship between a covariate and upper GI symptom prevalence.
In all situations, 2 investigators (DMS and SMC) determined study eligibility independently, with disagreements resolved by discussion or by a third investigator (CIC).
Two investigators (DMS and CIC) performed all data extraction. Data collected for each study included authors, year of publication, sample size, US geographic region in which the study was conducted, population studied including setting, use of random or convenience sample, age and sex, method of study data collection (eg, postal, Internet, selfcompleted or interviewer-administered questionnaire), response rate, duration or recall of symptoms, time frame of population sampling/study, criteria used to define upper GI symptoms (including whether a validated tool was used), upper GI symptom prevalence estimates, P value for the univariate relationship between a covariate and upper GI symptom, and effect size and P value for the multivariate relationship between a covariate and upper GI symptom.
The methodological quality of prevalence studies was assessed using the following attributes: (1) adequacy of sampling by assessing whether participants were sampled randomly or by convenience, (2) use of a validated questionnaire or tool to define upper GI disorders, and (3) sufficiently high response rate (>70%).44 We did not attempt to give a summary validity rating to each individual study in this systematic review, but rather used each criterion in sensitivity analysis as described below.
Numerators (n = number of patients reporting the symptom) and denominators (N = total number of patients evaluated) were extracted from each study in order to compute symptom prevalence with accompanying 95% confidence intervals (CIs) using the Wilson score method without continuity correction.45 The proportions of individuals in each study reporting symptoms were combined using a random-effects model to derive separate pooled prevalence rates of dyspeptic, gastroesophageal, or dyspeptic and/or gastroesophageal symptoms for all studies.46 Due to the wide variance identified in requested disease recall periods for PUD (upon endoscopy, the prior 12 months, or lifetime prevalence), an analysis pooling all studies was not conducted.
Between-study heterogeneity was assessed using the I2 statistic with a threshold of 50% used to define a statistically significant degree of heterogeneity. To assess for the potential for publication bias, we reviewed Egger’s weighted regression statistic P values (with P <.05 suggesting a higher likelihood of publication bias) and constructed funnel plots in which the standard error of each study was plotted against its prevalence (with an asymmetrical funnel plot suggesting publication bias; funnel plots available from authors upon request).
We conducted various subgroup and sensitivity analyses to examine the effect on dyspeptic, gastroesophageal, and dyspeptic and/or gastroesophageal symptom prevalence of various study characteristics and validity assessment criteria such as sampling (random or convenience); required duration or symptom recall (for dyspepsia, upper GI symptoms, and gastroesophageal symptoms, shorter recall included studies with <3-month disease recall; for PUD, shorter recall included studies with <12-month disease recall); US geographic region (national or regional sample); questionnaire/tool to ask about symptoms (validated or not); response rate (>70% or <70%); and year of publication (2006 to present or prior to 2006). For PUD, studies with shorter disease recall durations were pooled separately from studies with longer disease recall durations, and these analyses served as this outcome’s base-case results. No other PUD analyses were conducted due to the limited number of data points. The Cochran Q statistic was used to determine whether a statistically significant difference existed between subgroups. We considered P <.05 statistically significant for all analyses. All analysis was conducted using Stats- Direct version 2.7.2 (StatsDirect Ltd, Cheshire, England).
Qualitative synthesis of data depicting the relationship between various covariates and upper GI symptoms is reported using descriptive statistics.
Study Identification and Characteristics
Our literature search revealed 3096 nonduplicate citations. Upon title and abstract review, 3328 citations were excluded, leaving 578 citations for full-text review. Upon full-text review, 542 were excluded (Figure). Of note, 14 studies conducted in the Olmsted County, Minnesota, population were excluded from this analysis as they drew random samples out of the same study population and therefore were likely to have overlapping patient populations. A total of 36 citations, representing 24 unique studies, met our inclusion criteria.9-43 These included 9 studies reporting dyspeptic symptoms, 14 reporting gastroesophageal symptoms, 5 reporting dyspeptic and/or gastroesophageal symptoms, and 7 reporting PUD prevalence. These studies were all observational in nature and were published between 1991 and 2010. Of the 24 studies, 11 (45.8%) reported results of multivariate analysis with an upper GI symptom as the dependent variable (Appendixes 2-15, available at www. ajmc.com).
Key characteristics of included studies can be found in Table 1. Study sample sizes ranged from 248 to 226,953 patients. The total sample size for dyspeptic, gastroesophageal, dyspeptic and/or gastroesophageal symptoms and PUD studies was 14,181, 11,790, 58,701, and 284,922, respectively. Of the 24 unique studies, 9 (37.5%) used a randomly drawn sample, while the remaining 15 used convenience samples. Eleven studies (45.8%) sampled a national population, while the remaining studies drew participants from a regional area (city, state, or county). Eleven studies (45.8%) used validated questionnaires to elicit prevalence data on upper GI symptoms, with response rates from those reporting ranging between 17% and 92% (median of 70%).