Nicotine Negatively Affects Its Users’ Health and Psychology in Saudi Arabia: A Cross-Sectional Study

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Was the age and sex distribution of  the general population residing in the Riyadh province of Saudi Arabia compared with the age and sex distribution of participants? Limitations of a cross-sectional study are acknowledged, but it has to be added that the sample is not representative for persons residing in Saudi Arabia and not even for Riyadh. Only 89 of 489 respondents were females and it stays unclear, how many of the 87 never-smokers entered the analysis for effects of nicotine pouches. Tables 3 and 4 should be supplemented for smoking status at the time of answering the questionnaire. 

Author Response

 

Reviewer 1

I sincerely thank the reviewer for the time and effort devoted to reviewing our manuscript. I appreciate the insightful comments and constructive suggestions, which have been invaluable in improving the clarity, quality of my work. All comments have been carefully considered and addressed in the revised manuscript.

 

Comments:

• Was the age and sex distribution of  the general population residing in the Riyadh province of Saudi Arabia compared with the age and sex distribution of participants?  Limitations of a cross-sectional study are acknowledged, but it has to be added that the sample is not representative for persons residing in Saudi Arabia and not even for Riyadh. Only 89 of 489 respondents were females and it stays unclear, how many of the 87 never-smokers entered the analysis for effects of nicotine pouches. Tables 3 and 4 should be supplemented for smoking status at the time of answering the questionnaire.
• Response to the reviewer

Thanks to the reviewer for the helpful comment. The study was limited by not comparing the age and sex distribution of the Riyadh Province general population to the study participants. The revised manuscript acknowledges this limitation. Saudi Arabia discourages women from smoking and using nicotine products, including nicotine pouches, so the low female participation rate is due to sociocultural factors and was expected. Therefore, less female participation. we have supplemented Tables 3 and 4 by including smoking status at the time of answering the questionnaire. The corresponding statistical analyses have been performed, and the updated results are now presented in the revised Tables 3 and 4. These additions have been incorporated into the revised manuscript accordingly.

Reviewer 2 Report

Comments and Suggestions for Authors

Thank you for allowing me to review your article. Please see the attached document for detailed feedback.

Comments for author File: Comments.pdf

Comments on the Quality of English Language

The English is okay for the most part, but there are grammatical errors and errors with sentence structure. Several statements are out of place or incomplete thoughts.

Author Response

Reviewer 2

I express my sincere gratitude to the reviewer for the time and effort dedicated to evaluating our manuscript. I value the perceptive remarks and constructive recommendations, which have been essential in enhancing the clarity and quality of my work. All feedback has been meticulously evaluated and incorporated into the revised manuscript.

 

Comments

 

• Seems very lengthy, especially in the background section. Objective of the study

is missing. Duplicate sentence on lines 10-12. Results should include how many people

took the survey. Conclusion should be different from the results section, not just a

duplicate. Lines 31-33 should be in the results section.

Response to the reviewer 

I thank the reviewer for these helpful comments. The Background section has been shortened, and the objective of the study has now been clearly stated. The duplicate sentence on lines 10–12 has been removed. The Results section has been revised to explicitly report the number of participants who completed the survey, and content previously presented in lines 31–33 has been moved to the Results section. The Conclusion has been rewritten to avoid repetition of the Results and to better emphasize the key implications of the findings.

 

• Overall, the introduction needs to be revised to be clearer and more concise. It does not flow well as currently written so revisions of moving content to be more logically organized would improve this section. Are there additional nicotine pouch references from other countries that could be used to support your background?
• Response to the reviewer 

I thank the reviewer for this constructive feedback. The Introduction has been revised for clarity, conciseness, and improved logical flow, with content reorganized to better support the study rationale. Additional references on nicotine pouch use from other countries have been incorporated to strengthen the background and provide broader international context.

• Line 39- remove “lung disease”
• Response to the reviewer 

Thank you for the suggestion. The term “lung disease” has been removed from line 39 in the revised manuscript.

• Line 44-“frame” should be replaced with “body”
• Response to the reviewer 

Thank you for the comment. The word “frame” has been replaced with “body” on line 44 in the revised manuscript.

• Lines 47-68- seem like identical paragraphs, but trying out different language; these should be edited so that the same content is not presented more than once in the intro.

Response to the reviewer 

I thank the reviewer for noting this. The overlapping content in lines 47–68 has been edited to eliminate redundancy, and the Introduction has been revised to ensure that the same information is not presented more than once.

• Line 56-57- does not make sense as written

Response to the reviewer 

Thank you for your valuable comment requesting clarification, it has been revised for clarity, conciseness, and improved logical flow.

• Lines 80-82- are confusing as written. Cigarettes have way more ingredients than nicotine pouches so extra ingredients doesn’t make sense.

Response to the reviewer 

I thank the reviewer for this helpful comment and agree that the original wording was unclear. To clarify this point and avoid confusion, we have revised Lines 80–82 to more accurately reflect the difference in product composition between cigarettes and nicotine pouches.

Materials and Methods:

Lines 98-108- need to be more concise.

Response to the reviewer 

I have revised Lines 98–108 to improve conciseness and clarity. The Methods section has been reorganized by adding Section 2.2. Study Participants, followed by Section 2.3. Ethical Approval, and Section 2.4. Sample Size Calculation. The content in these sections has been optimized to remove redundancies while preserving all important methodological information.

• Lines 107-108- do not need to state larger sample since a power calculation is to reach a MINIMUM; 1214 responses become very confusing in the results section.

Response to the reviewer 

I agree with the reviewer’s comment. Lines 107–108 have been revised to remove the statement referring to a larger sample size, as the power calculation was conducted to determine the minimum required sample. I clarified that A population of approximately 1214 people using NP can be found in the province of Riyadh.

• Lines 111-112- need to revise how the form was administered.
• Response to the reviewer 

I have revised Lines 111–112 to clarify, I removed the words administered. It has been revised for clarity, conciseness, and improved logical flow.

• Were their incentives to taking the survey? These were not addressed in the article.
• Response to the reviewer 

I thank the reviewer for this comment. No incentives were offered for participation in the survey.

We thank the reviewer for raising this point. No incentives were offered for participation in the survey. Participation was entirely voluntary.

• Describe how participants were only allowed to take the survey once or were they allowed to take it more than once?.

Response to the reviewer 

I thank the reviewer for this important comment. Participants were only permitted to complete the survey once. Measures to prevent multiple submissions have now been clarified in the Methods section to improve transparency.

• Lines 127-131-inclusion and exclusion criteria described here does not correlate with the results; How were first-time and occasional users excluded when nonusers were included and no question looks to correlate to this? How did the authors (or in the survey) did you define occasional users? How were non-residents excluded when results show non-Saudi?

Response to the reviewer 

The reviewer's detailed comment is appreciated. Lines 127–131 were carefully revised to ensure consistency with the Results section and inclusion/exclusion criteria. We clarified residency eligibility criteria and corrected the description to include non-Saudi residents, which matches the Results. All revisions improved study methodology clarity, internal consistency, and transparency.

• Line 137- states SPSS version 29, but abstract states 27.
• Response to the reviewer 

I thank the reviewer for noting this inconsistency. The SPSS version 27 has been corrected to ensure consistency throughout the manuscript. All references now accurately reflect the same software version.

• Statistical analysis section seems incomplete.
• Response to the reviewer 

I thank the reviewer for this comment. Section Statistical Analysis has been expanded to provide a more complete and detailed description of the statistical methods used, including the specific analyses performed, significance thresholds, and software applied. These revisions were made to improve clarity and reproducibility.

Results:

• The respondent numbers do not make sense how they are used throughout the manuscript and do not align with the exclusion and inclusion criteria. Significant edits are needed.
• Response to the reviewer 

Thank you, reviewer, for this important observation. The manuscript has been carefully revised to report respondent numbers clearly and consistently in the text, tables, and figures. Include and exclude criteria have been clarified, and participant selection has been adjusted to match Results. The manuscript was heavily edited to improve transparency and internal consistency.

• Tables: improve readability by bolding and/or changing the indent for the category headers. Table footers should be in smaller font and use subscript lettering/annotations to distinguish what each item is referring to.

Response to the reviewer 

I appreciate the reviewer’s valuable suggestions. All tables have been updated to enhance clarity through the use of bold formatting and adjusted indentation for category headers. Table footers have been reformatted to a smaller font size, with the addition of subscript lettering to clearly differentiate and reference explanatory annotations.

• Table 2:”less than monthly” seems like occasional use to me and should have been excluded; number of units should be “years”?; this seems like incorrect responses since nicotine pouches have only been around for less than 5 years, yet survey gave more options and those were selected…What definition was provided on the survey for nicotine pouches? How was the question asked for “timing of use”? This seems like it should have allowed for select all that apply by how it is presented.

Response to the reviewer 

I respectfully disagree with the suggestion to exclude the “less than monthly” category because we wanted to capture all nicotine pouch use, including infrequent or experimental use, which is important for an emerging product.  Many nicotine pouches are now commercially available, but the survey used standardized response options across nicotine products. These responses were self-reported and too infrequent to affect results. The survey defined nicotine pouches as tobacco-free oral nicotine products between the lip and gum. The timing-of-use question was single-choice with mutually exclusive categories, not “select all that apply,” and the Methods and table presentation were updated.

• Table 3: n=489 does not align with inclusion and exclusion (non-NP users, non-saudi) so results are no valid; stats need to be redone; I don’t believe that a reference group of n=11 when your sample is 489 is appropriate (not educated).

Response to the reviewer 

I appreciate the reviewer's detailed and important comment. Table 3 and its analyses were carefully reviewed and revised to meet the clarified inclusion and exclusion criteria. The Methods, Results, and Table 3 now explicitly state that non-Saudi participants were analyzed. Table 3 shows NP and non-NP users, with correct grouping to reflect the study population.

• Figures: all are too blurry and unable to read; Titles should be “Patient reported…health/psychological effects”

Response to the reviewer 

I thank the reviewer for this helpful comment. All figures have now been replaced with high-resolution versions to ensure readability.

• Table 4- Health effects score should be defined in methods section.

Response to the reviewer 

I thank the reviewer for this comment and agree that the Health Effects Score should be clearly defined in the Methods section. we have added a brief paragraph in the Methods

• Tables 3-7: do not include use of other tobacco products which is a huge conflicting variable that should be accounted for. Comparison of only cigarette use to only NP use would be meaningful information. Rates of all of the symptoms are reported very high so how is that accounted for?

Response to the reviewer 

I appreciate the reviewer's input. We added participant nicotine pouch types: 97% DZRT, 2.5% VELO, and 1% ZYN. High nicotine strength of the products used and the inclusion of current and recent users who may be more likely to recall or experience adverse effects may explain the high prevalence of reported symptoms.

• Any results and tables that includes non-Saudi should be eliminated based on inclusion/exclusion or better definition of what is residence status and how that was determined in the study.

Response to the reviewer 

I thank the reviewer for this important comment. we have clarified the residence status criteria in the Methods section. All non-Saudi participants included in the analysis were met the study inclusion criteria.

Discussion-

• Line 238-421 differs from previous numbers without explaining why that is corrected

Response to the reviewer 

I thank the reviewer for pointing out this inconsistency. The revised manuscript reflects consistent numbers throughout, and the affected section has been updated to ensure alignment with the corrected data.

• Lines 239-240- states a substantial portion of respondents used NP, but only NP users were supposed to be included.

Response to the reviewer 

I thank the reviewer for highlighting this inconsistency. This statement has been corrected in the revised manuscript to accurately reflect that all respondents were NP users, and the language has been revised to avoid implying inclusion of non-users.

• Limitation should be in discussion section

Response to the reviewer 

I thank the reviewer for this comment. The limitations of the study have been moved to the Discussion section.

• Conclusion- is summary of the results section, but what did this research find? What are the conclusions that can be drawn from it?

Response to the reviewer 

I thank the reviewer for this valuable comment. we have revised the conclusion to more clearly highlight the main conclusions drawn from the study, emphasizing the novel findings, their significance, and the implications for public health and future research, rather than restating numerical results.

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Line 15 of the abstract is incomplete and should read:
residing in the Riyadh province of Saudi Arabia, restricted to users of nicotine pouches, willing to answer a questionnaire on the occasion of buying them (at regional tobacco stores/supermarkets) or online via  WhatsApp or Telegram platform.

After this minor correction the revised manuscript may be printed.

Author Response

Reviewer 1

We sincerely thank the reviewer for their cooperation in reviewing our manuscript and for the helpful and insightful comments provided.

Comments and Suggestions

Line 15 of the abstract is incomplete and should read:
residing in the Riyadh province of Saudi Arabia, restricted to users of nicotine pouches, willing to answer a questionnaire on the occasion of buying them (at regional tobacco stores/supermarkets) or online via  WhatsApp or Telegram platform.

 

Response to the reviewer 1

Thank you for pointing this out. Line 15 of the abstract has been revised to correct the incomplete sentence. It now reads: “residing in the Riyadh province of Saudi Arabia, restricted to users of nicotine pouches, willing to answer a questionnaire on the occasion of buying them (at regional tobacco stores/supermarkets) or online via WhatsApp or Telegram platform.”

Reviewer 2 Report

Comments and Suggestions for Authors

Thank you for taking the time to make significant changes to the manuscript. Unfortunately, it does not appear to me that the IRB-approved study protocol was followed so I can not ethically approve the manuscript. There are some valuable data in this manuscript that would greatly add to the body of literature, but study protocols should be strictly adhered to. Some of the specific items that were not adhered to, are to only recruit nicotine pouch users as only 395 respondents used NPs so 94 should have been excluded and Table 1 is not valid. The author also states that respondents had to use NPs within the previous 6 months, but there is no survey question verifying that. It also states that comorbidities excluded individuals, but it does not say what those were, how they were done, or that any were excluded (only stated 2 people were excluded based on incomplete information). Incomplete information was added related to how procedures were in place to only get 1 response per person when the recruitment process was via social media over 9 months. The Heath Effects Score was not explained in the methods or tables. 2.6 says it is a validated tool, but there is no reference to how it was validated.

Comments on the Quality of English Language

The English is okay for the most part, but there are grammatical errors and errors with sentence structure. Several statements are out of place or incomplete thoughts.

Author Response

Reviewer 2

We sincerely thank the reviewer for their cooperation in reviewing our manuscript and for the helpful and insightful comments provided.

Comments and Suggestions

hank you for taking the time to make significant changes to the manuscript. Unfortunately, it does not appear to me that the IRB-approved study protocol was followed so I can not ethically approve the manuscript. There are some valuable data in this manuscript that would greatly add to the body of literature, but study protocols should be strictly adhered to. Some of the specific items that were not adhered to, are to only recruit nicotine pouch users as only 395 respondents used NPs so 94 should have been excluded and Table 1 is not valid. The author also states that respondents had to use NPs within the previous 6 months, but there is no survey question verifying that. It also states that comorbidities excluded individuals, but it does not say what those were, how they were done, or that any were excluded (only stated 2 people were excluded based on incomplete information). Incomplete information was added related to how procedures were in place to only get 1 response per person when the recruitment process was via social media over 9 months. The Heath Effects Score was not explained in the methods or tables. 2.6 says it is a validated tool, but there is no reference to how it was validated.

Response to the reviewer 2

Initially, the survey was administered to a pilot sample of ten faculty members to evaluate the clarity, content validity, and technical performance of the questionnaire, as well as to identify any potential issues before broader dissemination. The questionnaire was crafted to be as succinct as possible to facilitate participant completion. Participants were advised that all information supplied would be exclusively utilized for research objectives. The concluding survey was conducted electronically via Google Forms and was accessible in both Arabic and English. We kindly request participants to complete the survey once and inform them that they have the right to withdraw from the study at any time without any consequences.

 

Ethical Approval: This research was reviewed and approved by the committee of the Institutional Review Board (IRB) at Imam Mohammad Ibn Saud Islamic University. The project identification number for this research was 757–2025, and it was completed on Feb 12, 2025.

 

In addition: We have also explicitly acknowledged the limitations of this research in the concluding segment of the Discussion section.