Review for 10.1186/s12876-023-02978-y (2023)

Title: Factors contributing to flares of ulcerative colitis in North India- A case-control study
Version: 2 Date: 22 May 2023
Reviewer's report:
Factors contributing to flares in ulcerative colitis in North India- A case control study
In this cross-sectional case-control study, authors evaluated factors associated with flare in
patients with ulcerative colitis in a tertiary center in north India. This study tried to explore
important research question, however there are many concerns in the methodology.
Major comments:
1. Authors have not used any standard, and validated questionnaire.
2. The major concern was recall bias as acknowledged by the authors
3. How did authors assess antibiotics/NSAID intake or infections. Have they reviewed
prescriptions, or medical records. If this information was based only on what was said by the
patients, it would be highly unreliable
4. How stress was assessed, was any standardized patient reported index followed?
5. What was considered as non-adherence? Was any specific definition used to define or grade?
6. Cases and controls were unequal in the number of patients. How was sample size determined?
7. Authors should acknowledge that the factors such as antibiotic use, non-adherence to
medications, CAM intake could be mere associations rather than true precipitants. Sometimes
active disease despite medications can prompt the patients to choose alternate medications or
antibiotics or even stop existing medications.
Therefore, if available the data on clinical state of these patients before antibiotic use/stopping
medications or CAM could help in answering this particular question
Minor comments:
1. In the introduction authors mentioned extensive disease and aggressive disease as factors
responsible for relapse in the brackets, but none of the references cited by authors support this.
Are there any studies that show extensive disease associated with increased risk of flares? If
so, please provide
2. Some of the references cited are more than 20 years old. Please update references
3. Authors mentioned in the introduction that possible factors for UC relapse were not
systematically evaluated in India. A prospective study with robust methodology done by Dhingra
et al, JGH, 2017 explored factors similar to this study. The authors should discuss this study’s
results in the discussion and explain how their study is different from this study.
4.  In the definition of remission Fcal <100 was included along with SCCAI<3. Was Fcal tested
in all patients, if so when was tested? Was Fcal done in cases as well?
5.  Patients admitted with infections were excluded. Does infection include GI infections?
6.  In the statistical analysis, SPSS version was not mentioned
7. There were minor formatting issues throughout the manuscript. Uniform format should be
followed for presenting p valued
8. In the results authors mentioned intake of milk products, but diet related questions were not
mentioned in the questionnaire
9. Actual questionnaire used by the authors in regional language can be presented as supplement
10. Authors mentioned in the methods that socio economic status was assessed but it was not
presented in the results. Was there any difference in educational status and SES of patients
between cases and controls