Lv M, Liu X, Huang KY, Xu LS, Che H, Yao MX, Wang FY. Outpatient visit frequency in patients with overlapping non-erosive reflux disease and epigastric pain syndrome: A multicenter study. World J Gastroenterol 2026; 32(28): 119326 [DOI: 10.3748/wjg.119326]
Corresponding Author of This Article
Feng-Yun Wang, MD, Chief Physician, Professor, Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, No. 1 Xiyuan Playground, Haidian District, Beijing 100091, China. 18810631761@163.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
research-article
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
Share the Article
Lv M, Liu X, Huang KY, Xu LS, Che H, Yao MX, Wang FY. Outpatient visit frequency in patients with overlapping non-erosive reflux disease and epigastric pain syndrome: A multicenter study. World J Gastroenterol 2026; 32(28): 119326 [DOI: 10.3748/wjg.119326]
Mi Lv, Kai-Yue Huang, Lu-Si Xu, Department of Gastroenterology (Spleen and Stomach Diseases), Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing 100091, China
Xin Liu, Graduate School, Beijing University of Chinese Medicine, Beijing 100029, China
Hui Che, Feng-Yun Wang, Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing 100091, China
Meng-Xi Yao, Department of Gastroenterology (Spleen and Stomach Diseases), Changping Hospital of Traditional Chinese Medicine, Beijing 102200, China
Author contributions: Lv M conceived and designed the study, supervised the project, acquired and curated data, performed formal analysis and investigation, developed the methodology and software, administered the project, acquired resources, validated results, created visualizations, and wrote the original draft; Liu X and Huang KY contributed equally to conceptualization and data curation; Liu X led the methodology and validation; Huang KY additionally contributed to methodology, software, and validation; Xu LS contributed equally to data curation, formal analysis, methodology, and software; Che H led the methodology and supervision, and contributed equally to reviewing and editing the manuscript; Yao MX contributed equally to conceptualization and data curation; Wang FY led data curation, funding acquisition, methodology, resources, supervision, and the review and editing of the manuscript. All authors participated in critically revising the manuscript for important intellectual content and have read and approved the final submitted version.
AI contribution statement: No artificial intelligence tools (such as ChatGPT, Grammarly, DeepL, or similar) were used in drafting or revising this manuscript. No part of the main text (Abstract, Introduction, Materials and Methods, Results, Discussion, or Conclusion) was generated by AI, either wholly or partially. No AI tool was used for language polishing, translation, data analysis, or writing assistance. No AI tool participated in the study design, data processing, interpretation of results, or any other research activity. All figures, tables, and images in the manuscript were independently created by the authors, and none were generated by AI. We confirm that this manuscript is the original work of our research team.
Supported by the National Natural Science Foundation of China, No. 82374434 and No. 82174363; the Youth Science Foundation Project of the National Natural Science Foundation of China, No. 82205104; and the Excellent Young Scientific and Technological Talent Training Program of the Fundamental Scientific Research Business Expenses of China Academy of Chinese Medical Sciences, No. ZZ16-YQ-002.
Institutional review board statement: The study protocol was approved by the Ethics Committees of all participating centers (Approval No. 2022XLA041-1 and No. 2022-039).
Informed consent statement: Informed consent was obtained from all individual participants included in this study.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: With the consent of the corresponding author, we will be able to provide the raw data.
Corresponding author: Feng-Yun Wang, MD, Chief Physician, Professor, Institute of Digestive Diseases, Xiyuan Hospital of China Academy of Chinese Medical Sciences, No. 1 Xiyuan Playground, Haidian District, Beijing 100091, China. 18810631761@163.com
Received: January 26, 2026 Revised: February 26, 2026 Accepted: April 1, 2026 Published online: July 28, 2026 Processing time: 170 Days and 19.1 Hours
Abstract
BACKGROUND
The overlap between non-erosive reflux disease (NERD) and epigastric pain syndrome (EPS) is common in China, but its clinical profile and healthcare burden are poorly defined.
AIM
To characterize patients with NERD-EPS overlap and identify factors linked to frequent gastroenterology clinic visits.
METHODS
In a multicenter, cross-sectional study, 800 consecutive patients with NERD-EPS overlap were enrolled from four tertiary hospitals in China. Data were collected via questionnaires on socio-demographics, clinical manifestations, medication use, visit frequency, and psychological distress (4-item Patient Health Questionnaire). Multivariable ordinal logistic regression identified factors independently associated with higher visit frequency.
RESULTS
Among the 800 patients (mean age 44.50 ± 14.43 years; 66.70% female), 42.40% had ≥ 3 clinic visits. Independent risk factors for more frequent visits included older age [adjusted odds ratio (aOR) = 1.02], longer NERD duration (aOR = 1.004), higher psychological distress (aOR = 1.08 per 1-point 4-item Patient Health Questionnaire increase), mixed labor (aOR = 3.37) or physical labor (aOR = 1.91), married status (aOR = 2.05), proton pump inhibitor use (aOR = 1.39), and Chinese herbal preparation use (aOR = 6.64). A significant synergistic interaction on visit frequency was found between proton pump inhibitor and herbal use (interaction aOR = 29.06, P < 0.001).
CONCLUSION
Frequent outpatient visits in NERD-EPS overlap is driven by a combination of demographic factors, chronicity, psychological comorbidity, and complex medication patterns, rather than symptoms alone. These findings highlight the strong association between psychological distress and frequent visits, suggesting that integrating psychological screening into routine care may help identify at-risk patients. Prospective studies are needed to determine whether psychosomatic interventions can effectively reduce healthcare utilization in this population.
Core Tip: In this first large-scale multicenter study of overlapping non-erosive reflux disease and epigastric pain syndrome in China, frequent healthcare visits were driven not by symptom severity, but by a profile combining chronicity, psychological distress, and complex medication patterns. A striking interaction between proton pump inhibitor and Chinese herbal medicine use identified a high-need subgroup. These findings highlight the importance of an integrated, psychosomatic approach addressing both peripheral and central mechanisms to reduce the healthcare burden in this population.
Citation: Lv M, Liu X, Huang KY, Xu LS, Che H, Yao MX, Wang FY. Outpatient visit frequency in patients with overlapping non-erosive reflux disease and epigastric pain syndrome: A multicenter study. World J Gastroenterol 2026; 32(28): 119326
Non-erosive reflux disease (NERD), the most prevalent subtype of gastroesophageal reflux disease (GERD), is characterized by typical reflux symptoms in the absence of endoscopic evidence of mucosal breaks, accounting for 60%-70% of GERD cases[1]. Epigastric pain syndrome (EPS), a major subtype of functional dyspepsia within the spectrum of functional gastrointestinal disorders (FGIDs), presents with bothersome epigastric pain or burning, often associated with visceral hypersensitivity and gastroduodenal dysmotility[2,3].
The overlap between NERD and EPS is highly common in gastroenterology clinics in China. These patients often present with more complex and refractory symptoms, greater psychological comorbidity, and a higher healthcare burden[4]. FGID overlaps predominantly affect individuals of working age, leading to substantial socioeconomic costs due to absenteeism and reduced productivity[3,5,6].
The co-occurrence of NERD and EPS may be underpinned by shared pathophysiological mechanisms, including visceral hypersensitivity, brain-gut axis dysregulation, psychosocial comorbidity, and similar patterns of low-grade inflammation and microbiota alterations[7,8]. This provides a rationale for understanding this overlap syndrome within the biopsychosocial model. However, large-scale clinical studies specifically focusing on patients with overlapping NERD and EPS, particularly those systematically investigating clinical characteristics and healthcare utilization within a biopsychosocial framework, are lacking in China.
A comprehensive understanding of the sociodemographic and clinical characteristics, psychological status, treatment patterns, and healthcare use in this population is crucial. It can help identify the core drivers of frequent healthcare-seeking, guide personalized and integrated management, and inform public health strategies to optimize resource allocation and alleviate the associated disease burden.
Designed as the first large-scale, multicenter, cross-sectional study in China targeting this overlapping population, this research aims to comprehensively assess the clinical profile - including symptom triggers, comorbidities, and psychological and sleep status - based on the biopsychosocial model. Furthermore, it will objectively evaluate healthcare resource utilization by documenting medication history and gastroenterology clinic visit frequency over the preceding three months and explore its associated factors.
MATERIALS AND METHODS
Study design and participants
This multicenter, cross-sectional study was conducted between March 2022 and October 2024 at four tertiary care traditional Chinese medicine (TCM) hospitals in China. The study protocol was approved by the Ethics Committees of all participating centers (Approval No. 2022XLA041-1 and No. 2022-039). The detailed recruitment procedures, inclusion and exclusion criteria, and the specific diagnostic criteria for NERD and EPS have been comprehensively described in our previous study[9]. In brief, the study enrolled 800 patients aged 18 years to 75 years who concurrently met the diagnostic criteria for both NERD and EPS. To ensure a homogeneous study population and exclude structural pathologies, all patients underwent an upper gastrointestinal endoscopy following symptom onset. This evaluation confirmed the absence of erosive esophagitis, peptic ulcers, and other organic diseases that could confound the diagnosis. The raw data can be obtained after receiving consent from the corresponding author.
Questionnaire and assessments
Data were collected using a structured questionnaire covering the following domains.
Sociodemographic and clinical characteristics: Age, sex, body mass index, occupation, education level, marital status, residence, disease duration, symptom triggers, comorbidities, medication use, and gastroenterology clinic visits within the past three months.
Patient-reported outcomes: Assessed using the following validated instruments. Detailed descriptions of each instrument, including scoring criteria and clinical cut-offs, have been previously reported in our published cross-sectional study[9]. A summary is provided below: (1) Reflux symptoms: The GERD Questionnaire (GERD-Q; score range 0-18, higher scores indicate more significant symptom impact)[10]; (2) Anxiety and depression: The 4-item Patient Health Questionnaire (The PHQ-4, which combines the two-item Generalized Anxiety Disorder-2 anxiety scale and the two-item PHQ-2 depression scale, was selected for the following reasons. First, it has been extensively validated and demonstrates good reliability and validity for screening anxiety and depression in various populations, including gastroenterology settings, as supported by studies published in leading psychiatry journals[11,12]. Second, during our pilot testing, we observed that longer questionnaires with more extensive items on anxiety and depression often triggered discomfort or resistance among middle-aged participants, who frequently questioned the relevance of such “non-gastrointestinal” questions to their condition, leading to incomplete responses. The ultra-brief nature of the PHQ-4 minimized respondent burden and reduced such resistance, thereby improving overall response rates and data quality in this specific patient population. Score range 0-12, higher scores indicate greater severity of anxiety/depressive symptoms[11,12]; (3) Somatic symptom burden: The PHQ-15 (score range 0-30, higher scores indicate greater somatic symptom severity)[13,14]; (4) Gastrointestinal symptoms: The Gastrointestinal Symptom Rating Scale (GSRS; score range 15-60, higher scores indicate more severe gastrointestinal symptoms)[15,16]; and (5) Sleep quality: The Self-Rating Scale of Sleep (SRSS; score range 10-50, higher scores indicate more severe sleep disturbances)[17]. The primary outcome was healthcare burden, operationalized as the self-reported number of gastroenterology clinic visits in the preceding three months. For analysis, visits were categorized as 1-2, 3-4, or ≥ 5.
The recall period for medication use and gastroenterology clinic visit frequency was limited to the preceding three months. This timeframe was deliberately chosen based on the diagnostic criteria for EPS, which requires the presence of active symptoms within the past three months in the context of a disease course of at least six months[2,3]. Therefore, this three-month window is not only methodologically common in healthcare utilization research to balance recall accuracy with data completeness, but also clinically meaningful for capturing the recent disease activity and associated healthcare burden most relevant to patients with NERD-EPS overlap.
Statistical analysis
All analyses were performed using IBM SPSS Statistics (Version 26.0). Continuous variables with normal distribution are presented as mean ± SD; non-normally distributed variables as median (interquartile range); and categorical variables as n (%). Univariable analyses were first conducted to assess the association between individual variables and the ordinal outcome of clinic visit frequency (1-2, 3-4, ≥ 5 visits). Ordinal logistic regression was used as the primary analytical method. Variables with a significance level of P < 0.05 in univariable analyses were included as candidate variables in the multivariable model to enhance robustness. While scale scores (PHQ-4, PHQ-15, GSRS, SRSS) were presented using established clinical cut-offs in descriptive analyses, they were treated as continuous variables in regression models to avoid information loss and to precisely estimate their association with visit frequency. Multicollinearity was assessed using the variance inflation factor (VIF), with VIF < 5 indicating low collinearity. Results from the regression analyses are reported as adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Model fit was evaluated using the -2 Log-likelihood (-2 LL) and the Pearson goodness-of-fit test. All tests were two-sided, with P < 0.05 considered statistically significant.
RESULTS
Patient characteristics
As shown in Table 1, the 800 patients with NERD-EPS overlap had a mean age of 44.50 ± 14.43 years, with a female-to-male ratio of 5:3. Symptom recurrence or exacerbation was triggered by dietary factors in 72.88% (n = 583) of patients and by emotional fluctuations in 47.75% (n = 382). Within the preceding three months, 69.38% (n = 555) had used Chinese herbal preparations, and 40.88% (n = 327) had used proton pump inhibitors (PPIs). A total of 42.38% (n = 339) had visited a gastroenterology clinic three or more times. Based on PHQ-15 and SRSS scores, 39.63% (n = 317) and 22.50% (n = 180) of patients had moderate-to-severe somatization and sleep disturbances, respectively.
Table 1 Baseline sociodemographic and clinical characteristics of study patients with non-erosive reflux disease and epigastric pain syndrome overlap, n (%).
Non-parametric tests (Mann-Whitney U, Kruskal-Wallis H, or Spearman’s correlation coefficient ρ, as appropriate) were used to identify variables significantly associated with outpatient visit frequency (P < 0.05). Univariable analysis revealed that a higher number of clinic visits was significantly associated with older age, occupation type, being married, longer NERD duration, the presence of comorbidities (chronic pharyngitis, cardiovascular disease, or endocrine/metabolic diseases), and higher scores on the GERD-Q, PHQ-4, PHQ-15, SRSS, and GSRS (all P < 0.05; Table 2). Furthermore, recent use of PPIs, prokinetics, mucosal protectants, probiotics, and Chinese herbal preparations were also significantly associated with increased visit frequency (P < 0.05; Table 2).
Table 2 Univariable analysis of factors associated with gastroenterology clinic visit frequency.
Variables with P < 0.05 from the univariable analysis were included in the multivariable ordinal logistic regression model. Dummy variables were created for unordered categorical variables. No significant multicollinearity was detected (all VIF < 5, all tolerance > 0.1). The model fitting information indicated that the final model was a significant improvement over the intercept-only model (χ2 = 255.14, P < 0.001), confirming that the set of independent variables significantly predicted the outcome. Goodness-of-fit tests (Pearson χ2 P = 0.75; Deviance χ2 P = 1.00) indicated a good model fit. The Nagelkerke R2 value of 0.32 suggested that the model explained approximately 31.80% of the variance in the dependent variable, indicating a moderate level of explanatory power.
Multivariable analysis identified the following as independent risk factors for increased outpatient visit frequency: Older age, engagement in mixed (mental-physical) or physical labor, being married, longer NERD duration, greater psychological distress (higher PHQ-4 score), use of PPIs, use of Chinese herbal preparations, and the presence of cardiovascular disease in Table 3.
Table 3 Multivariable ordinal logistic regression analysis of factors independently associated with higher outpatient visit frequency.
To assess potential effect modification, interaction tests were conducted based on theoretical considerations and clinical experience for factors hypothesized to interact, such as age and PPI use, PHQ-4 score and PPI use, and the combination of PPI and Chinese herbal preparation use. The results revealed a statistically significant interaction between PPI use and Chinese herbal preparation use when comparing patients with 1-2 clinic visits to those with 3-4 visits in the past three months (aOR = 29.06, 95%CI: 8.38-100.72, P < 0.001). This indicates a significant synergistic effect on visit frequency when both medications were used concurrently. However, this interaction was not statistically significant in the comparison between the 3-4 visits and ≥ 5 visits groups (aOR = 3.03, 95%CI: 0.72-12.76, P = 0.13). None of the other interaction terms tested reached statistical significance (P > 0.05), suggesting no significant effect modification by these factor combinations on outpatient visit frequency in Table 4.
Table 4 Interaction effects between significant predictors on outpatient visit frequency.
In this first large multicenter cross-sectional study of Chinese patients with overlapping NERD and EPS, we identified a substantial healthcare burden, with 42.38% of patients reporting ≥ 3 gastroenterology clinic visits within the preceding 3 months. This frequency markedly exceeds rates reported for general dyspepsia populations in routine care and endoscopic settings, highlighting the unique challenges posed by symptom overlap. This finding aligns with the global consensus that overlap among FGIDs increases disease severity and healthcare utilization[4,18-20].
Our multivariable analysis elucidated multiple factors driving high visit frequency. A longer NERD disease duration (aOR = 1.004) reflects the cumulative effect of disease chronicity on healthcare needs. Notably, while the GERD-Q, GSRS, and SRSS assess reflux symptoms, gastrointestinal symptom profiles, and sleep disturbance, respectively, none were independent factors associated with frequent visits. This finding indicates a disconnect between symptom severity and healthcare resource use, consistent with some international studies[21-24]. This may stem from the fact that healthcare-seeking decisions in FGID patients are often driven less by symptom intensity and more by symptom interpretation, coping styles, and comorbid psychological distress[25-28]. Specifically, gastrointestinal symptoms or sleep problems alone, if not perceived as “uncontrollable” or “threatening to health”, may not trigger frequent visits. Conversely, when these symptoms coexist with significant anxiety/depression (high PHQ-4 scores), the latter amplifies illness perception and healthcare-seeking motivation, making psychological variables more critical drivers, underscoring the central role of brain-gut interactions[27,28].
Among the significant factors, older age was independently associated with increased visit frequency, consistent with trends of physiological decline, increased comorbidities [e.g., comorbid cardiovascular disease (aOR = 1.72) was associated with higher visit rates in our study], and potentially greater healthcare-seeking propensity across the lifespan[29,30]. Married status (aOR = 2.05) might reflect social support from family health concerns but could also prompt more active treatment seeking due to family responsibility pressures. We observed a counter-intuitive finding: Patients engaged in physical or mixed labor had significantly higher visit frequencies than those in mental occupations. This suggests that visit behavior differences may not be solely driven by disease severity but rather by socio-economic structures and derived health behaviors across occupational groups. For Chinese “white-collar” workers, lower clinic visit rates might stem from high “opportunity costs” (e.g., career development concerns from interrupting important work) and the lack of social consensus for their common health issues (e.g., chronic stress, emotional distress) as “legitimate” reasons for sick leave, prompting greater use of alternatives like online consultations or corporate clinics not captured by traditional statistics. Conversely, health impairments in physical laborers (e.g., acute pain, physical strain) are often more objective and urgent, but taking leave often means direct income loss. This structural pressure might lead them to “endure minor illnesses, delay major ones” until symptoms become severe enough to prevent work, making each visit represent a greater disease burden and ultimately increasing statistical visit risk. Thus, visit frequency differences likely reflect “hidden barriers” to healthcare access and group differences in the “legitimacy” of health problems rather than true health status comparisons.
Disease characteristics and psychological comorbidity constituted another core dimension. We observed that nearly 40% of patients had moderate-to-severe somatic symptoms (PHQ-15). A higher PHQ-4 score was associated with increased clinic visit frequency (aOR = 1.08), further supporting the prevalence of psychological factors in this overlap syndrome. Therefore, our findings support the potential utility of integrating ultra-brief psychological instruments like the PHQ-4 into routine gastroenterology clinic assessments to identify patients with high psychological comorbidity. However, as this is a cross-sectional study, interventional research is required to determine whether early screening and subsequent intervention for anxiety/depressive symptoms can effectively reduce unnecessary repeated visits.
Regarding treatment patterns, a highly instructive finding was that both PPI use (aOR = 1.39) and Chinese herbal preparation use (aOR = 6.64) were significantly associated with higher visit frequency. This likely reflects these medications serving as proxies for “refractory” or “high symptom burden” patients rather than indicating treatment ineffectiveness. Clinically, physicians tend to prescribe higher-dose or longer-course PPIs for patients with suboptimal response to standard therapy or complex symptoms, while patient pursuit of Chinese herbal preparations often signifies dissatisfaction with conventional therapy or a desire for personalized management. This interpretation is strongly supported by interaction analysis: Combined PPIs and Chinese herbal preparation use showed a substantial synergistic effect (aOR = 29.06) in specific comparisons, clearly identifying a patient subgroup with the most complex conditions, refractory symptoms, and highest healthcare needs. Nevertheless, the wide confidence interval surrounding this estimate (95%CI: 8.38-100.72) indicates limited precision, likely attributable to the relatively small sample size of the 3-4 visits group (n = 168) from which this interaction was derived. Further stratification within this subgroup resulted in sparse data and model instability. Therefore, while this finding is clinically suggestive, it warrants confirmation in larger, prospective studies with greater statistical power to examine such interaction effects. This aligns with studies in other conditions where lower response rates to standard therapy often lead patients to seek combination or alternative therapies[31-33]. For this specific subgroup, more aggressive stratified management should be initiated, such as implementing integrated gastroenterology and psychosomatic medicine/psychology clinics for simultaneous physiological and psychological intervention. Concurrently, enhanced patient education and expectation management, explaining the benign nature of symptoms and brain-gut interaction mechanisms, can help establish realistic treatment expectations and reduce excessive healthcare-seeking driven by “illness uncertainty”.
Beyond these findings, several broader considerations help contextualize the high visit frequency observed in our study. First, the doctor-patient relationship itself may influence therapeutic outcomes - in FGIDs where organic pathology is absent, inappropriate communication or misalignment of expectations can perpetuate ineffective therapy and repeated consultations[34]. Second, the symptoms of epigastric pain and burning may reflect central sensitization disorders rather than peripheral pathology alone, explaining the limited efficacy of acid suppression and the potential need for neuromodulators[35]. Pain processing in the central nervous system integrates source localization, intensity, stress response, emotional valence, cognitive interpretation, and inhibitory control - all potentially dysregulated in these patients[36]. Third, healthcare utilization patterns are inevitably shaped by system-level factors including specialist availability and regional dietary habits. In particular, dietary tryptophan metabolites via the kynurenine pathway (e.g., xanthurenic acid, quinolinic acid, indican, p-cresol) can significantly modulate peripheral and central nervous system function when produced in excess[37,38], representing an important avenue for future research.
Our study has limitations. The cross-sectional design precludes causal inference. Importantly, the recruitment of patients exclusively from tertiary care TCM hospitals introduces a potential selection bias. Patients seeking care at TCM hospitals may have a pre-existing preference for or higher expectations of Chinese herbal preparations. This could have influenced the strong association observed between herbal use and visit frequency (aOR = 6.64) and its synergistic interaction with PPIs. Consequently, the prevalence of herbal medicine use and its relationship with healthcare utilization may be overestimated compared to the general population of NERD-EPS patients seen in non-TCM or primary care settings. This limits the generalizability of our findings related to treatment patterns. Additionally, medication data were self-reported, which may be subject to recall bias; future studies should incorporate electronic prescription data for improved accuracy. Furthermore, our primary outcome was operationalized solely as the frequency of gastroenterology clinic visits, a measure that does not capture other important dimensions of burden, such as hospitalizations, emergency department visits, productivity loss, or direct and indirect medical costs. The data for this outcome were based on patient self-report over the preceding three months, which is subject to recall bias. While this three-month recall period was selected to align with the EPS diagnostic criteria (requiring active symptoms within this window) and to capture the most clinically relevant recent burden, we acknowledge that patients may under- or over-report their actual visit counts. This potential misclassification could have biased our estimates, possibly towards the null. Future studies should ideally link patient-reported data with electronic medical records or administrative claims data to obtain more objective and precise measurements of healthcare utilization and to enable a more comprehensive assessment of economic impact. Another limitation is that we did not collect data on individual income or health insurance type (including reimbursement rates), which are important socioeconomic determinants of healthcare-seeking behavior[39]. The absence of these variables may have introduced residual confounding, potentially influencing the observed associations between occupational categories, medication use, and visit frequency. For instance, patients with higher income or better insurance coverage may have different healthcare-seeking patterns that could partially explain the differences we observed across occupational groups. Future research should incorporate these socioeconomic factors to better disentangle the complex drivers of healthcare utilization in this population.
CONCLUSION
This study demonstrates that high outpatient visit frequency among Chinese patients with NERD-EPS overlap exhibits a disconnect from symptom severity measures (GERD-Q, GSRS, SRSS). The core drivers are not the symptoms themselves but rather a combination of demographic characteristics (older age, specific occupations, married status), disease chronicity (NERD duration), prominent psychological comorbidity (anxiety/depression), and complex medication patterns indicative of refractoriness. This finding emphasizes the greater predictive value of psychosocial factors and treatment history compared to symptom scores alone in clinical assessment. This suggests that future clinical management could potentially benefit from extending beyond symptom control to focus on systematic psychological screening and stratification of high-risk patients. Further research is warranted to test whether implementing integrated care models combining gastroenterology and psychosomatic medicine can more precisely and effectively reduce the healthcare burden in this population.
Van de Bruaene C, Carbone F, Van den Houte K, Colomier E, Raymenants K, Broeders B, Balsiger LM, Jones MP; AEGIS Working Group, Vanuytsel T, Tack J. Navigating the Maze of Functional Dyspepsia: Emergence of a New Entity, Postprandial Epigastric Pain Syndrome.Clin Gastroenterol Hepatol. 2025;23:2607-2615.e5.
[RCA] [PubMed] [DOI] [Full Text][Cited by in RCA: 3][Reference Citation Analysis (0)]
Wauters L, Dickman R, Drug V, Mulak A, Serra J, Enck P, Tack J; ESNM FD Consensus Group, Accarino A, Barbara G, Bor S, Coffin B, Corsetti M, De Schepper H, Dumitrascu D, Farmer A, Gourcerol G, Hauser G, Hausken T, Karamanolis G, Keszthelyi D, Malagelada C, Milosavljevic T, Muris J, O'Morain C, Papathanasopoulos A, Pohl D, Rumyantseva D, Sarnelli G, Savarino E, Schol J, Sheptulin A, Smet A, Stengel A, Storonova O, Storr M, Törnblom H, Vanuytsel T, Velosa M, Waluga M, Zarate N, Zerbib F. United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on functional dyspepsia.United European Gastroenterol J. 2021;9:307-331.
[RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)][Cited by in Crossref: 89][Cited by in RCA: 106][Article Influence: 21.2][Reference Citation Analysis (1)]
Sperber AD, Freud T, Aziz I, Palsson OS, Drossman DA, Dumitrascu DL, Fang X, Fukudo S, Ghoshal UC, Kellow J, Khatun R, Okeke E, Quigley EMM, Schmulson M, Simren M, Tack J, Whitehead WE, Whorwell P, Bangdiwala SI. Greater Overlap of Rome IV Disorders of Gut-Brain Interactions Leads to Increased Disease Severity and Poorer Quality of Life.Clin Gastroenterol Hepatol. 2022;20:e945-e956.
[RCA] [PubMed] [DOI] [Full Text][Cited by in Crossref: 78][Cited by in RCA: 93][Article Influence: 23.3][Reference Citation Analysis (0)]
Lyu M, Ke X, Wang JH, Ye B, Li YF, Zhou ZH, Huang SG, Wang M, Ma SP, Su JP, Zhou XL, Che H, Wang FY. [Investigation on the distribution characteristics of functional gastrointestinal disorders in tertiary traditional Chinese medicine hospitals].Zhongguo Zhongxiyi Jiehe Xiaohua Zazhi. 2025;33:447-454.
[PubMed] [DOI] [Full Text]
Basnayake C, Kamm MA, Stanley A, Wilson-O'Brien A, Burrell K, Lees-Trinca I, Khera A, Kantidakis J, Wong O, Fox K, Talley NJ, Liew D, Salzberg MR, Thompson AJ. Standard gastroenterologist versus multidisciplinary treatment for functional gastrointestinal disorders (MANTRA): an open-label, single-centre, randomised controlled trial.Lancet Gastroenterol Hepatol. 2020;5:890-899.
[RCA] [PubMed] [DOI] [Full Text][Cited by in Crossref: 92][Cited by in RCA: 93][Article Influence: 15.5][Reference Citation Analysis (0)]
Aziz I, Palsson OS, Törnblom H, Sperber AD, Whitehead WE, Simrén M. The Prevalence and Impact of Overlapping Rome IV-Diagnosed Functional Gastrointestinal Disorders on Somatization, Quality of Life, and Healthcare Utilization: A Cross-Sectional General Population Study in Three Countries.Am J Gastroenterol. 2018;113:86-96.
[RCA] [PubMed] [DOI] [Full Text][Cited by in Crossref: 180][Cited by in RCA: 157][Article Influence: 19.6][Reference Citation Analysis (3)]
Kavalieratos D, Corbelli J, Zhang D, Dionne-Odom JN, Ernecoff NC, Hanmer J, Hoydich ZP, Ikejiani DZ, Klein-Fedyshin M, Zimmermann C, Morton SC, Arnold RM, Heller L, Schenker Y. Association Between Palliative Care and Patient and Caregiver Outcomes: A Systematic Review and Meta-analysis.JAMA. 2016;316:2104-2114.
[RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)][Cited by in Crossref: 870][Cited by in RCA: 857][Article Influence: 85.7][Reference Citation Analysis (0)]
Flores-Arriaga J, Aso MC, Izagirre A, Sperber AD, Palsson OS, Bangdiwala SI, Lanas Á, Bujanda L, Lobo B, Alonso-Cotoner C, Sánchez-Pla Á, Santos J. Prevalence and description of disorders of gut-brain interaction in Spain according to the results of the Rome Foundation Global Epidemiology Study.Neurogastroenterol Motil. 2023;35:e14582.
[RCA] [PubMed] [DOI] [Full Text][Cited by in Crossref: 3][Cited by in RCA: 5][Article Influence: 1.7][Reference Citation Analysis (0)]
Corresponding Author's Membership in Professional Societies: Committee for Research on Digestive Disease Drugs, China Association of Chinese Medicine, President/Chairman; Spleen and Stomach Diseases Branch, China Association of Chinese Medicine, 202457017.
Specialty type: Gastroenterology and hepatology
Country of origin: China
Peer-review report’s classification
Scientific quality: Grade A, Grade B, Grade C
Novelty: Grade A, Grade A, Grade D
Creativity or innovation: Grade A, Grade A, Grade D
Scientific significance: Grade A, Grade A, Grade C
P-Reviewer: Chojnacki J, Professor, Poland; Xu X, MD, PhD, Associate Professor, China S-Editor: Wang JJ L-Editor: A P-Editor: Zhang L
