Peer Review History

Original SubmissionMarch 9, 2022
Decision Letter - Lucy J Troup, Editor

PONE-D-22-07067The association of state cannabis vaping prevalence with the e-cigarette or vaping product-use associated lung injuryPLOS ONE

Dear Dr. Blaha,

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.

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Kind regards,

Lucy J Troup, Ph.D

Academic Editor

PLOS ONE

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2. 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 If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references.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 If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.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:

Thank you so much for your patience with this process. It is getting extremely hard to find reviewers.

[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: Partly

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

Reviewer #2: Yes

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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: Yes

Reviewer #2: Yes

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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

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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: This is important work and this reviewer sincerely appreciates the undertaking of these authors. There is one important problem with this manuscript which I suspect could be easily resolved by the authors: no method of adjustment of estimates for state cannabis policy category is explained other than the method of categorization itself, which is insufficient to understand the implications of assumptions made in adjustment or the strategy used. If authors would briefly explain their approach to adjustment by category in 1-2 sentences, I suspect it would render this manuscript quite technically sound and would clarify the appropriateness and rigor of the statistical analysis.

Line 2: Given that the investigation ultimately found an inverse association between state cannabis vaping prevalence and EVALI case burden, authors might consider a revised title. (For example, “Inverse association…”)

Line 23: During the EVALI outbreak, cases also occurred among people who were not exposed to THC-containing products, and among those not exposed to VEA. Therefore, authors should strongly consider modifying the word “associated” with a precedent “primarily” or “largely”.

Line 25: VEA was not used in all THC-containing e-liquids. Would strongly recommend adding the word “sometimes” after “additive”.

Line 30: I am not recommending that adjustment is further defined in the abstract. However, it is important that authors describe their method of adjustment in Methods.

Line 47: This sentence is not correct as written. Many persons diagnosed with EVALI had underlying medical conditions. Would recommend either deleting “otherwise healthy”, or moving it to the end of the sentence with a qualifier. (For example: “was an acute lung injury seen in persons who reported e-cigarette use before the onset of symptoms, many of whom were otherwise healthy.”)

Line 63: Materials and Methods is not complete without a description of the method of adjustment for cannabis policy type.

Line 86: Adjusted *how*, though? With what underlying assumptions or interpretation of each category of cannabis policy? This matters very much for the interpretation of results.

Line 89: The inclusion of this sensitivity analysis is a nice addition.

Line 122 (Table 2): This table has a hanging asterisk – which numbers are adjusted for cannabis policy?

Line 129: How did authors account for state cannabis policy? Without explanation of the strategy for adjustment in Methods, one wonders whether these results are a possible artifact of this adjustment.

Line 136: Please consider avoiding use of the phrase "black market". This phrase perpetuates the symbolism of white as "good" and black as "bad" that is unfortunately already quite pervasive.

Line 137: As CDC does not use the phrase “black-market”, this alone is not a correct citation.

Line 149: Authors might consider including in stated limitations the possibility that not all EVALI cases were captured during the epidemic.

Reviewer #2: This was a very well designed study, using existing information on Cannabis use, vaping, Cannabis laws, and EVALI cases. My only suggestion is to add a statement on the large width of several of the confidence intervals in Table 1, page 11, EVALI cases per million population.

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Reviewer #1: No

Reviewer #2: Yes: Gordon Vrdoljak

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Revision 1

Reviewer #1:

This is an important work, and this reviewer sincerely appreciates the undertaking of these authors. There is one important problem with this manuscript which I suspect could be easily resolved by the authors: no method of adjustment of estimates for state cannabis policy category is explained other than the method of categorization itself, which is insufficient to understand the implications of assumptions made in adjustment or the strategy used. If authors would briefly explain their approach to adjustment by category in 1-2 sentences, I suspect it would render this manuscript quite technically sound and would clarify the appropriateness and rigor of the statistical analysis.

We greatly appreciate your thorough review of our manuscript. States were defined by whether they had recreational and/or medical cannabis laws or none. In our regression analysis, we included recreational and medical cannabis states as indicator variables (yes/no), leaving prohibitive states as reference. We have included in the methods section how we defined and modeled state cannabis policy for our analysis.

Lines 83-86

“Linear regression models were used to examine the cross-sectional association between cannabis vaping prevalence and EVALI cases per million population, adjusted for state cannabis legalization policies. Indicator variables were used for medical and recreational cannabis states, leaving prohibitive states as reference.”

Additionally, even when included as a 3-level categorical variable, we obtain the same estimates for the constant and the coefficient of cannabis vaping prevalence. Thank you.

Line 2: Given that the investigation ultimately found an inverse association between state cannabis vaping prevalence and EVALI case burden, authors might consider a revised title. (For example, “Inverse association…”)

Thank you for this suggestion. We have edited the title accordingly.

“The inverse association of state cannabis vaping prevalence with the e-cigarette or vaping product-use associated lung injury”

Line 23: During the EVALI outbreak, cases also occurred among people who were not exposed to THC-containing products, and among those not exposed to VEA. Therefore, authors should strongly consider modifying the word “associated” with a precedent “primarily” or “largely”.

Line 25: VEA was not used in all THC-containing e-liquids. Would strongly recommend adding the word “sometimes” after “additive”.

We agree that while a majority of hospitalized EVALI patients reported using THC-containing products (82%), there were some who were not exposed to THC-containing e-liquids. We have modified the statement. We have also added “sometimes” after “additive.”

Lines 23-26

“The e-cigarette or vaping product-use-associated lung injury (EVALI) epidemic was primarily associated with the use of e-cigarettes containing tetrahydrocannabinol (THC)- the principal psychoactive substance in cannabis, and vitamin-E-acetate- an additive sometimes used in informally sourced THC-containing e-liquids.”

Line 30: I am not recommending that adjustment is further defined in the abstract. However, it is important that authors describe their method of adjustment in Methods.

Thank you. We have described the method of adjustment under the Methods Section.

Line 47: This sentence is not correct as written. Many persons diagnosed with EVALI had underlying medical conditions. Would recommend either deleting “otherwise healthy” or moving it to the end of the sentence with a qualifier. (For example: “was an acute lung injury seen in persons who reported e-cigarette use before the onset of symptoms, many of whom were otherwise healthy.”)

Thank you for this suggestion as well. We have edited accordingly.

Lines 46-48

“The e-cigarette or vaping product-use-associated lung injury (EVALI) epidemic in the United States (US) was an acute lung injury seen in persons who reported e-cigarette use before the onset of symptoms, many of whom were otherwise healthy”

Line 63: Materials and Methods is not complete without a description of the method of adjustment for cannabis policy type.

Line 86: Adjusted *how*, though? With what underlying assumptions or interpretation of each category of cannabis policy? This matters very much for the interpretation of results.

Thanks again for this clarifying question. States were defined by whether they had recreational and/or medical cannabis laws or none. In our regression analysis, we included recreational and medical cannabis states as indicator variables (yes/no), leaving prohibitive states as reference.

Lines 83-86

“Linear regression models were used to examine the cross-sectional association between cannabis vaping prevalence and EVALI cases per million population, adjusted for state cannabis legalization policies. Indicator variables were used for medical and recreational cannabis states, leaving prohibitive states as reference.”

Line 89: The inclusion of this sensitivity analysis is a nice addition.

Thanks for acknowledging this.

Line 122 (Table 2): This table has a hanging asterisk – which numbers are adjusted for cannabis policy?

We have deleted the hanging asterisk. The models presented are adjusted for the indicator cannabis policy variables.

Line 129: How did authors account for state cannabis policy? Without explanation of the strategy for adjustment in Methods, one wonders whether these results are a possible artifact of this adjustment.

We have included statements in the methods to clarify this. Please see above. Indicator variables were used to represent recreational and medical states (yes/no). These indicator variables were included in the linear regression models. Thank you.

Line 136: Please consider avoiding use of the phrase "black market". This phrase perpetuates the symbolism of white as "good" and black as "bad" that is unfortunately already quite pervasive. Line 137: As CDC does not use the phrase “black-market”, this alone is not a correct citation.

We appreciate this correction. We have deleted “black market” and kept “informal sources” as used by the CDC.

“These findings, therefore, suggest that there may not be a direct, simple link between a state’s cannabis vaping prevalence and EVALI cases, but rather the relationship is likely more nuanced, supporting the CDC’s hypothesis that the EVALI outbreak is likely reflective of access to informal sources of THC-containing e-liquids”

Line 149: Authors might consider including in stated limitations the possibility that not all EVALI cases were captured during the epidemic.

We have included this as a limitation.

“Additionally, it is likely that not all EVALI cases were captured during the epidemic; hence, these numbers may underrepresent the true extent of the outbreak.” 

Reviewer #2:

This was a very well-designed study, using existing information on Cannabis use, vaping, Cannabis laws, and EVALI cases. My only suggestion is to add a statement on the large width of several of the confidence intervals in Table 1, page 11, EVALI cases per million population.

Thank you for reviewing our manuscript. We have included this as a limitation and added a footnote to Table 1.

“Additionally, the CDC reported the number of EVALI cases as a range, therefore accounting for the wide confidence intervals of the EVALI cases per million population.”

Editorial 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

We have followed all the style requirements in the revised version of our manuscript. Thank you.

2. 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.

All references cited are correct and complete. Thank you.

Attachments
Attachment
Submitted filename: Response To Reviewers.docx
Decision Letter - Lucy J Troup, Editor

The inverse association of state cannabis vaping prevalence with the e-cigarette or vaping product-use associated lung injury

PONE-D-22-07067R1

Dear Dr. Blaha,

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.

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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,

Lucy J Troup, Ph.D

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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

Reviewer #2: All comments have been addressed

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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

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: 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

Reviewer #2: 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

Reviewer #2: 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 the thorough explanations and the added content to Methods -- this addresses all the previous concerns of this reviewer.

Reviewer #2: Thank you for addressing all the comments posed by all of the reviewers. The paper is greatly improved.

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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

Reviewer #2: Yes: Gordon Vrdoljak

**********

Formally Accepted
Acceptance Letter - Lucy J Troup, Editor

PONE-D-22-07067R1

The inverse association of state cannabis vaping prevalence with the e-cigarette or vaping product-use associated lung injury

Dear Dr. Blaha:

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. Lucy J Troup

Academic Editor

PLOS ONE

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