The association between symptoms of gastroesophageal reflux disease and perceived stress: A countrywide study of Sri Lanka

Nilanka Wickramasinghe; Ahthavann Thuraisingham; Achini Jayalath; Dakshitha Wickramasinghe; Nandadeva Samarasekara; Etsuro Yazaki; Niranga Manjuri Devanarayana

doi:10.1371/journal.pone.0294135

Peer Review History

Original SubmissionMay 18, 2023
23 Jun 2023 Decision Letter - Karthik Gangu, Editor PONE-D-23-13957The association between Gastroesophageal Reflux Disease and stress: A countrywide study of Sri LankaPLOS ONE Dear Dr. wickramasinghe, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Aug 07 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. 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The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For more information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. In your revised cover letter, please address the following prompts: a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially sensitive information, data are owned by a third-party organization, etc.) and who has imposed them (e.g., an ethics committee). 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Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: No Reviewer #2: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: Dear Authors, It was a pleasure to read your work titled “The association between Gastroesophageal Reflux Disease and stress: A countrywide study of Sri Lanka”. Overall, a good study with clinical implications. Few concerns Major As pointed out by the authors, this is a study on association of various symptoms to the presence/degree of stress. Not necessarily GERD as the study participants did not undergo any formal testing to evaluate for the presence of true evidence of pathological acid reflux. Many of these symptoms can be seen in GERD by are also shared by other etiologies such as functional dyspepsia, functional heartburn, reflux hypersensitivity to name a few. As such, I recommend modifying the title and discussion to reflect this. Minor Overall, there are multiple long, complex sentences throughout this manuscript. Some have grammatical errors too. This forces the reader stop and retrace the sentence to understand the discussion. I would recommend revising to make the flow smooth and easy on the reader. Results section is a little confusing and feels scattered Lines 163 to 166. Unclear what the authors are conveying here. Lines 187 to 189. Do the authors mean "patients with chest pain reported higher stress compared to those without chest pain, but did not reach statistical significance". This sentence is difficult to follow. Discussion Line 250. "This pattern is observed in our results as well as seen in Table 3." I would elaborate this a little and clarify. Lines 273 to 276. The idea is conveyed but the sentence should be revised. "Increased anxiety and stress levels are postulated to affect the GI tract and esophagus in many ways, subsequently triggering true GERD, as well as other conditions which rise to similar symptoms such as reflux hypersensitivity and functional heartburn" Line 316 introduces the abbreviation - FGID without expanding/explaining this. Please expand. Line 326 This sentence is incomplete "The current study also identified some associated factors such as younger age, being single, and a low education status" -- Associated with what should be clarified. Lines 330 to 334. I think this can be made more succinct. Reviewer #2: Overall, a well written manuscript on a relevant topic. here are my comments - 1. One fundamental issue with the definition of GERD is based on symptomatology and may encompass several patients with functional dyspepsia and other esophageal motility disorder. This brings the idea of stress directly related to GERD into question. Further detailed explanation of association of symptomatology and perceived stress level would be helpful. 2. Provide further explanation regarding lack of symptomatic improvement with GERD medications (what medications were tried and for what duration) in patients with high levels of stress. ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: Yes: Harishankar Gopakumar, MD, FACP Reviewer #2: No ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0294135.r001
Revision 1
4 Aug 2023 Author Response 9th July 9, 2023 Dear Editors and Reviwers, Thank you very much for the comprehensive review of the paper. It helped to greatly enhance the research idea. We have done the required revisions. This document shows the point-by-point responses to the corrections and questions posed by both editors and reviewers. My responses are given in red text for ease of reading. Please let me know if there are any mistakes I can revise if not done so far. Sincerely Nilanka Wickramasinghe When submitting your revision, we need you to address these additional requirements. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf Done 2. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For more information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. In your revised cover letter, please address the following prompts: a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially sensitive information, data are owned by a third-party organization, etc.) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent. b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. We will update your Data Availability statement on your behalf to reflect the information you provide. We have uploaded the data set to a repository as requested. Please see data set https://doi.org/10.7910/DVN/WGSNWT available at HARVARD Dataverse https://dataverse.harvard.edu/file.xhtml?fileId=7236399&version=DRAFT Dataset Citation wickramasinghe, nilanka, 2023, "The association between symptoms of Gastroesophageal Reflux Disease and stress: A countrywide study of Sri Lanka", https://doi.org/10.7910/DVN/WGSNWT, Harvard Dataverse, DRAFT VERSION, UNF:6:MUMqzMNc1gcPWqZzivvsiA== [fileUNF] File Citation wickramasinghe, nilanka, 2023, "The association between symptoms of Gastroesophageal Reflux Disease and stress: A countrywide study of Sri Lanka", https://doi.org/10.7910/DVN/WGSNWT, Harvard Dataverse, DRAFT VERSION; DataforstressinGERDpaper.tab [fileName], UNF:6:MUMqzMNc1gcPWqZzivvsiA== [fileUNF] 3. Please upload a new copy of Figure 1 as the detail is not clear. Please follow the link for more information: https://blogs.plos.org/plos/2019/06/looking-good-tips-for-creating-your-plos-figures-graphics/ https://blogs.plos.org/plos/2019/06/looking-good-tips-for-creating-your-plos-figures-graphics/ Done 4. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information. Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes ________________________________________ 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ________________________________________ 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: No - data shared Reviewer #2: Yes ________________________________________ 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ________________________________________ 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: Dear Authors, It was a pleasure to read your work titled “The association between Gastroesophageal Reflux Disease and stress: A countrywide study of Sri Lanka”. Overall, a good study with clinical implications. Few concerns Major As pointed out by the authors, this is a study on association of various symptoms to the presence/degree of stress. Not necessarily GERD as the study participants did not undergo any formal testing to evaluate for the presence of true evidence of pathological acid reflux. Many of these symptoms can be seen in GERD by are also shared by other etiologies such as functional dyspepsia, functional heartburn, reflux hypersensitivity to name a few. As such, I recommend modifying the title and discussion to reflect this. Revised title as recommended. “The association between symptoms of Gastroesophageal Reflux Disease and perceived stress: A countrywide study of Sri Lanka” Edits made for discussion section as well. Minor o Overall, there are multiple long, complex sentences throughout this manuscript. Some have grammatical errors too. This forces the reader stop and retrace the sentence to understand the discussion. I would recommend revising to make the flow smooth and easy on the reader. We have revised accordingly with use of expert help and software to reduce complex sentences and grammar errors. o Results section is a little confusing and feels scattered We have rearranged the results section with advice given by the reviewer. o Lines 163 to 166. Unclear what the authors are conveying here. The lines 163 to 166 were rewritten as given below. “When the score obtained for GERD was correlated with the PSS score for the total population, there was a significant correlation in the total population (R 0.242, p<0.001). When the same correlation was done for the subgroups of GERD and controls as seen in Figure 1, a higher correlation was found for those with GERD, (R 0.256 and 0.137 respectively), though results were statistically significant (p<0.001) for both GERD and controls.” o Lines 187 to 189. Do the authors mean "patients with chest pain reported higher stress compared to those without chest pain, but did not reach statistical significance". This sentence is difficult to follow. Yes. We have rewritten as the reviewer has suggested. “Patients with chest pain reported higher stress levels than those without, though the result was not statistically significant. (48.4% and 57.9%, Chi-square test, p= 0.124).” o Discussion Line 250. "This pattern is observed in our results as well as seen in Table 3." I would elaborate this a little and clarify. It’s a line erronousely added. We changed from line 241 to 251 it to fit the reviewer’s comment at the very beginning regarding the GERD definition. “A similar study conducted in Saudi Arabia found that GERD symptoms were significantly (p < 0.05) associated with high perceived stress (OR = 1.30, 95% CI: 1.01–1.44) which is compatible with our results. [31] Furthermore, another study reported that 60% of GERD patients perceived increased symptoms during stressful times. [32] This is compatible with our results which show aggravation of symptoms in 41.8% of subjects during periods of stress. A previous study has reported a significantly lower level of anxiety, in diagnosed patients with GERD compared to functional heartburn [33] A prospective study in Sweden also found that anxiety was a risk factor for developing functional dyspepsia, but not GERD symptoms. [34] According to these studies, increased levels of anxiety are more likely to be associated with GERD symptoms due to functional heartburn than true GERD. However, since our study did not do pH impedance testing we cannot show the difference in stress levels between subjects with functional disorders and those objectively diagnosed with GERD.” o Lines 273 to 276. The idea is conveyed but the sentence should be revised. "Increased anxiety and stress levels are postulated to affect the GI tract and esophagus in many ways, subsequently triggering true GERD, as well as other conditions which rise to similar symptoms such as reflux hypersensitivity and functional heartburn" Thank you for revising and making the sentence more understandable. We added the sentence revised by the reviewer. o Line 316 introduces the abbreviation - FGID without expanding/explaining this. Please expand. Corrected. Mucosal barrier dysfunction and increased permeability of the gastrointestinal mucosa are also said to be part of the pathophysiology for Functional Gastrointestinal Disorders (FGIDs). o Line 326 This sentence is incomplete "The current study also identified some associated factors such as younger age, being single, and a low education status" -- Associated with what should be clarified. Corrected. The current study also identified some associated factors such as younger age, being single, and a low education status with symptoms of GERD. (Table 2). o Lines 330 to 334. I think this can be made more succinct. We have edited the lines as given below “Studies have shown that anxiety, depression, and other mood disorders increase the odds of developing GERD-related symptoms significantly.[71] [71] In this community-based study, we did not assess such psychiatric conditions due to practical difficulties.” Reviewer #2: Overall, a well written manuscript on a relevant topic. here are my comments - 1. One fundamental issue with the definition of GERD is based on symptomatology and may encompass several patients with functional dyspepsia and other esophageal motility disorder. This brings the idea of stress directly related to GERD into question. Further detailed explanation of association of symptomatology and perceived stress level would be helpful. The discussion is amended and edited according to the reviewer comments We have also changed the title and discussion related to “association of stress to GERD symptoms” as opposed to just “GERD” 2. Provide further explanation regarding lack of symptomatic improvement with GERD medications (what medications were tried and for what duration) in patients with high levels of stress. The methodology section was revised to include the following. “The participants were questioned on whether they used any type of proton pump inhibitors (using commonly used generic and trade names to recall), at least once, during the past three months. They were also questioned on whether the use of PPIs for heartburn, during the past three months, had “no GERD symptom relief” or “achieved GERD symptom relief.” ________________________________________ Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0294135.r002
16 Oct 2023 Decision Letter - Dong Keon Yon, Editor PONE-D-23-13957R1The association between Gastroesophageal Reflux Disease and stress: A countrywide study of Sri LankaPLOS ONE Dear Dr. wickramasinghe, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Nov 30 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript: A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols. We look forward to receiving your revised manuscript. Kind regards, Dong Keon Yon, MD, FACAAI, FAAAAI Academic Editor PLOS ONE Journal Requirements: Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. Additional Editor Comments: Please see minor comments from me and the reviewers. #1. The Chi-square test was used for nominal data, the Mann-Whitney test was used for Wickramasinghe ratio data, and backward logistic regression was used to assess the independent association between factors. -> Please cite the statistical guideline (DOI: https://doi.org/10.54724/lc.2022.e1). #2. A two-sided P less than 0.05 considered significance -> Please add this sentence. #3. Please receive English Editing Service. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #1: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes ****** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: Thank you for incorporating the recommended changes. I believe it is now good for publication with a few minor edits if possible. 1. Under results section (Lines 38 to 39) "The adjusted odds ratio for GERD symptoms was 1.96 times higher (95% confidence interval 1.50-2.55) between moderate to high-stress level and low-stress level participants. I feel this sentence should be restructured to "The adjusted odds ratio for GERD symptoms was 1.96 times higher (95% confidence interval 1.50-2.55) in the moderate to high-stress level compared to the low-stress level participants. 2. Introduction section lines 60-62. "GERD is shown to be triggered by many risk factors, including obesity, smoking, etc., and the pathophysiology of this condition is very complex. Conversely, mental stress is a well- recognized and important risk factor for GERD symptoms in patients" Comment - Why say "conversely" here? It is not a contradictory statement to the preceding one. I recommend amending this. ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0294135.r003
Revision 2
23 Oct 2023 Author Response Journal Requirements: Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. We have revised and edited the references and referencing list to be up-to-date, and have removed some references. Additional Editor Comments: Please see minor comments from me and the reviewers. #1. The Chi-square test was used for nominal data, the Mann-Whitney test was used for Wickramasinghe ratio data, and backward logistic regression was used to assess the independent association between factors. -> Please cite the statistical guideline (DOI: https://doi.org/10.54724/lc.2022.e1). We have cited the references and advised. #2. A two-sided P less than 0.05 considered significance -> Please add this sentence. We have added this sentence as advised. “A two-sided p less than 0.05 was considered as significant.” #3. Please receive English Editing Service. We used Grammarly software and an expert in English to go through the paper. Reviewer #1: Thank you for incorporating the recommended changes. I believe it is now good for publication with a few minor edits if possible. 1. Under results section (Lines 38 to 39) "The adjusted odds ratio for GERD symptoms was 1.96 times higher (95% confidence interval 1.50-2.55) between moderate to high-stress level and low-stress level participants. I feel this sentence should be restructured to "The adjusted odds ratio for GERD symptoms was 1.96 times higher (95% confidence interval 1.50-2.55) in the moderate to high-stress level compared to the low-stress level participants. Thank you for the comments. We have restructured the lines as advised. 2. Introduction section lines 60-62. "GERD is shown to be triggered by many risk factors, including obesity, smoking, etc., and the pathophysiology of this condition is very complex. Conversely, mental stress is a well- recognized and important risk factor for GERD symptoms in patients" Comment - Why say "conversely" here? It is not a contradictory statement to the preceding one. I recommend amending this. We have amended the lines as advised. “Mental stress too is a well- recognized and important risk factor for GERD symptoms in patients.” Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0294135.r004
26 Oct 2023 Decision Letter - Dong Keon Yon, Editor The association between symptoms of Gastroesophageal Reflux Disease and perceived stress; A country wide study of Sri Lanka PONE-D-23-13957R2 Dear Dr. wickramasinghe, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Dong Keon Yon, MD, FACAAI, FAAAAI Academic Editor PLOS ONE Additional Editor Comments (optional): This is an excellent paper. Reviewers' comments: https://doi.org/10.1371/journal.pone.0294135.r005
Formally Accepted
31 Oct 2023 Acceptance Letter - Dong Keon Yon, Editor PONE-D-23-13957R2 The association between symptoms of Gastroesophageal Reflux Disease and perceived stress: A countrywide study of Sri Lanka Dear Dr. Wickramasinghe: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Dong Keon Yon Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0294135.r006

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