PONE-D-22-02306Trends in proton pump inhibitor use, reflux esophagitis, and various upper gastrointestinal symptoms from 2010 to 2019 in JapanPLOS ONE

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Reviewer #1: I applaud the Authors for a thorough review and the impressive patient population included in the study. The manuscript presents a decade of experience in prescribing antacid medications in Japan which mirrors the international trend which has seen an increase in the prescription of PPIs worldwide. Importantly it sheds a light on the issue of overprescription of PPIs for the wrong symptoms (such as the most common: bloating). However before publication several points need to be addressed:

1) The tables appear to be overly convoluted and difficult to read, mostly because of an abundance of duplicate entries from the FSSG questionnaire (Heartburn, heartburn while bending, heartburn after meals). I wonder if a simplification of the symptoms categories would be possible including clustering similar symptoms together (heartburn) and/or removing symptoms which are not very specific to GERD (feeling sick after meals) as tables are very difficult to read in their present form. Perhaps splitting symptoms into typical (HB, regurgitation, chest pain and dysphagia) and atypical could help. All the 12 entries could be left as is in table 5.

2) It would be interesting to know the schedule and indications for EGD surveillance and whether the authors subscribe to ASGE guidelines

3) It seems like the most common symptom the patient report is bloating, which is not usually improved by PPIs administration. There is however an improvement in patients reporting this symptom amongst PPI takers. This should be expanded upon in the discussion.

4) It would be interesting to know how many of the patients underwent anti-reflux surgery for their symptoms. I know its not very popular in Japan but perhaps some of the patients underwent this route.

5) each figure should have a description for easier interpretability

6) given the detail of the database it would be good to know if authors also collected other medical history hinting to PPIs side effects such as PNA, C. Difficlile Colitis, fractures and esophageal cancer rates.

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Reviewer #1: Yes: Filippo Filicori, MD

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Trends in proton pump inhibitor use, reflux esophagitis, and various upper gastrointestinal symptoms from 2010 to 2019 in Japan

PONE-D-22-02306R1

Dear Dr. Yamamichi,

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.

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Kind regards,

Rasa Zarnegar, MD

Academic Editor

PLOS ONE

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