Reviewer’ s report
Title: Factors correlated with drug use for constipation: perspectives from the 2016 open Japanese
National Database
Version: 0Date: 23 Jun 2020
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research
question(s) (brief or other article types: is there a clear objective)?Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for the
objective?Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with technical rigor to allow
confidence in the results?No - there are minor issues
STATISTICS - Is the use of statistics in the manuscript appropriate?
No - there are issues with the statistics in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically sound?
If not, can revisions be made to make the work technically sound?Probably - with minor revisions
PEER REVIEWER COMMENTS:GENERAL COMMENTS:
The authors have investigated the risk factors for constipation drug use using the open JapaneseNational Database (NDB). Lots of researches have been done using the NDB since it was publiclyreleased to researchers in 2011. Few of them were conducted by Yonekura (2019); Shinichiro et al.(2018); and Hirose et al. (2020). The authors have also claimed that this was the first ecologicalstudy of drugs used to alleviate constipation in the Japanese population. This will help the clinicalpractitioners consider the risk factors while managing constipation.
The authors have used the data from the open Japanese National Database (NDB) and have
applied ecologic study to make large-scale comparisons among the 47 cities in Japan (as indicated
in the supplementary file). They have analyzed the data with multiple linear regression (MLR).
This helped minimize the impact of the confounding for the ecological fallacy, which is inherent incase of ecologic studies.
The authors have to show the associated F-values and coefficient of determination (R2) values
while applying the MLR analysis. It would be far better if they applied the multilevel modelling(MLM) techniques, which would overcome the ecological fallacy even better and help examinethe contextual effects.
REQUESTED REVISIONS:
The authors are suggested to clarify the issues related to the alternative statistical analysis andstrategy to minimize the inherent ecological fallacy.ADDITIONAL REQUESTS/SUGGESTIONS:General comments:*Keep 'stimulant laxatives' instead of 'stimulative laxatives' in table 5 and figure 2.*Keep figure labelling in figures 1 and 2.
Specific comments:
Title: You may reformat the title in the compounding or hanging style such as "Factors correlatingwith drug use for constipation: perspective/evaluation/analysis from the 2016 open JapaneseNational Database" or something like this, to make the title more attractive. You may think on it, ifyou find it alright.
Background:
*Lines 55-57: Specify the country where the prevalence was the lowest (i.e., 2%) and where it wasthe highest (i.e., 27%).*Lines 65-66: Cite the reference where it was reported.
Methods:
*It will be better if you rewrite Methods section under relevant subheadings such as study type,data source (for this secondary data source), data extraction, inclusion and exclusion criteria,sampling technique employed, statistical analysis and other.*Lines 82-84: Give examples of each category.*It would be better if the authors presented the background information to NDB along with themodality of getting access to the NDB in the Methods section of the present research. Thefollowing reference may help you in this direction:Hirose N, Ishimaru M, Morita K, Yasunaga H. A review of studies using the Japanese NationalDatabase of Health Insurance Claims and Specific Health Checkups. Annals of ClinicalEpidemiology 2020;2(1):13-26.It's just a suggestion; you may keep the abovementioned information related to NDB from otherresearches as well.
Results:
*Lines 104-105: Since your topic deals with constipation and lactulose can be used forconstipation, you have excluded lactulose from your study. Clarify the reason for its exclusion.
This also applies for the lines 177-178 in the Discussion section.
*Lines 135-136: How could you confirm that only aging was the independent risk factor? Didn't
other risk factors influence magnesium laxatives/purgatives?
Discussion:
*Lines 148-149: You have mentioned that you have reported the results of an ecological analysisof health insurance claims (prescriptions) for the alleviation of constipation. Mention this studydesign in the Methods section as well. Since ecological (ecologic) studies (also known as analysesof secular trends) help analyze data from a single region and examine how the trend changes overtime, or analyze data from a single time period and compare how the data differ from region to
region or country to country, such study design seems relevant here. Here, you have presented the
comparative view of 47 cities in the supplementary Excel file. However, discussion of the inherentproblem of the ecological fallacy (i.e., confounding specific to ecological studies), which occurswhen relationships for groups are also true for individuals, is missing in the Limitation section.The authors have rightly applied multiple linear regression (MLR) analysis to overcome theconfounding. It would be far better if they applied the multilevel modelling (MLM) techniques,which overcome the ecological fallacy even better and help examine the contextual effects.*Lines 149-150: Cite the references to those previous studies.*Lines 151-153: How could you confirm this? Did you extensively search for the information inthe literature?*Lines 158-160: This information seems irrelevant for the present study. Also, clarify whether theinformation from these references have any connection or relation with the topic.*Lines 170-172: Rewrite the sentence clearly.
Conclusion, Lines 184-185: How did you confirm that that this was the first ecological study of
drugs used to alleviate constipation in the Japanese population? Did you extensively search theliterature?Abbreviations: You may remove most of the well-known abbreviations from the list. This will
save space.
Tables 4-7: Clarify why you did not keep the same predictors for the MLR analysis. If you did so,
it would be easier to compare the results or outputs. It would also make it easy to merge the tablesinto one composite table with different outcomes with the same predictors.
Publons Reviewer Recognition. Springer Nature can send verification of this review directly to
Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service,please click on the “Yes” option below. Your name, email address, title of the reviewed
manuscript, name of the journal, and date of your review submission (the “Review Data”) will
then be transmitted to Publons upon publication of the manuscript. If you have already registeredat Publons, they will notify you of the receipt of this review and update your profile as per yoursettings and their policy. If you are not registered with Publons, you will receive an email fromthem asking you to register in order for them to be able to recognize your review on your newprofile page. Publons may use the Review Data to generate derivative metadata for the benefit ofPublons and you as a reviewer, carefully considering the sensitivity of such information. Forexample, Publons may verify your record as a reviewer by updating your profile published on itswebservice if you have registered for such service or help editors to identify candidate reviewers.
Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms
No
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
NoDoes the work include the necessary controls?
If not, please specify which controls are required in your comments to the authors.
No
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
NoAre you able to assess any statistics in the manuscript or would you recommend an
additional statistical review?If an additional statistical review is recommended, please specify what aspects require furtherassessment in your comments to the editors.
I am able to assess the statisticsQuality of written English
Please indicate the quality of language in the manuscript:
Needs some language corrections before being published
Declaration of competing interests
Please complete a declaration of competing interests, considering the following questions:
1. Have you in the past five years received reimbursements, fees, funding, or salary from an
organisation that may in any way gain or lose financially from the publication of thismanuscript, either now or in the future?
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose
financially from the publication of this manuscript, either now or in the future?
3. Do you hold or are you currently applying for any patents relating to the content of the
manuscript?
4. Have you received reimbursements, fees, funding, or salary from an organization that holds
or has applied for patents relating to the content of the manuscript?
5. Do you have any other financial competing interests?
6. Do you have any non-financial competing interests in relation to this paper?
If you can answer no to all of the above, write 'I declare that I have no competing interests' below.
If your reply is yes to any, please give details below.
This reviewer has been recruited by a partner organization, Research Square. Reviewers with
declared or apparent competing interests are not utilized for these reviews. This reviewer hasagreed to publication of their comments online under a Creative Commons Attribution Licenseattributed to Research Square and was paid a small honorarium for completing the review within a
specified timeframe. Honoraria for reviews such as this are paid regardless of the reviewer
recommendation.
Reviewer Publication Consent. I agree for my report to be made available under an Open Access
Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manu-script is accepted for publication. Any comments that I do not wish to be included in the publishedreport have been included as confidential comments to the editor, which will not be published.Ifyou are not happy for us to publish this report, please contact the editorial office before completingthe review.If you wish, you can include your name in your published report. Please note you mustdecide whether to include your name at the start of the process and confirm this decision wheneverprompted. If you change your decision later, we will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report.
(default)
Reviewer’ s report
Title: Factors correlated with drug use for constipation: perspectives from the 2016 open Japanese
National Database
Version: 0Date: 23 Jun 2020
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research
question(s) (brief or other article types: is there a clear objective)?Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for the
objective?Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with technical rigor to allow
confidence in the results?No - there are minor issues
STATISTICS - Is the use of statistics in the manuscript appropriate?
No - there are issues with the statistics in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically sound?
If not, can revisions be made to make the work technically sound?Probably - with minor revisions
PEER REVIEWER COMMENTS:GENERAL COMMENTS:
The authors have investigated the risk factors for constipation drug use using the open JapaneseNational Database (NDB). Lots of researches have been done using the NDB since it was publiclyreleased to researchers in 2011. Few of them were conducted by Yonekura (2019); Shinichiro et al.(2018); and Hirose et al. (2020). The authors have also claimed that this was the first ecologicalstudy of drugs used to alleviate constipation in the Japanese population. This will help the clinicalpractitioners consider the risk factors while managing constipation.
The authors have used the data from the open Japanese National Database (NDB) and have
applied ecologic study to make large-scale comparisons among the 47 cities in Japan (as indicated
in the supplementary file). They have analyzed the data with multiple linear regression (MLR).
This helped minimize the impact of the confounding for the ecological fallacy, which is inherent incase of ecologic studies.
The authors have to show the associated F-values and coefficient of determination (R2) values
while applying the MLR analysis. It would be far better if they applied the multilevel modelling(MLM) techniques, which would overcome the ecological fallacy even better and help examinethe contextual effects.
REQUESTED REVISIONS:
The authors are suggested to clarify the issues related to the alternative statistical analysis andstrategy to minimize the inherent ecological fallacy.ADDITIONAL REQUESTS/SUGGESTIONS:General comments:*Keep 'stimulant laxatives' instead of 'stimulative laxatives' in table 5 and figure 2.*Keep figure labelling in figures 1 and 2.
Specific comments:
Title: You may reformat the title in the compounding or hanging style such as "Factors correlatingwith drug use for constipation: perspective/evaluation/analysis from the 2016 open JapaneseNational Database" or something like this, to make the title more attractive. You may think on it, ifyou find it alright.
Background:
*Lines 55-57: Specify the country where the prevalence was the lowest (i.e., 2%) and where it wasthe highest (i.e., 27%).*Lines 65-66: Cite the reference where it was reported.
Methods:
*It will be better if you rewrite Methods section under relevant subheadings such as study type,data source (for this secondary data source), data extraction, inclusion and exclusion criteria,sampling technique employed, statistical analysis and other.*Lines 82-84: Give examples of each category.*It would be better if the authors presented the background information to NDB along with themodality of getting access to the NDB in the Methods section of the present research. Thefollowing reference may help you in this direction:Hirose N, Ishimaru M, Morita K, Yasunaga H. A review of studies using the Japanese NationalDatabase of Health Insurance Claims and Specific Health Checkups. Annals of ClinicalEpidemiology 2020;2(1):13-26.It's just a suggestion; you may keep the abovementioned information related to NDB from otherresearches as well.
Results:
*Lines 104-105: Since your topic deals with constipation and lactulose can be used forconstipation, you have excluded lactulose from your study. Clarify the reason for its exclusion.
This also applies for the lines 177-178 in the Discussion section.
*Lines 135-136: How could you confirm that only aging was the independent risk factor? Didn't
other risk factors influence magnesium laxatives/purgatives?
Discussion:
*Lines 148-149: You have mentioned that you have reported the results of an ecological analysisof health insurance claims (prescriptions) for the alleviation of constipation. Mention this studydesign in the Methods section as well. Since ecological (ecologic) studies (also known as analysesof secular trends) help analyze data from a single region and examine how the trend changes overtime, or analyze data from a single time period and compare how the data differ from region to
region or country to country, such study design seems relevant here. Here, you have presented the
comparative view of 47 cities in the supplementary Excel file. However, discussion of the inherentproblem of the ecological fallacy (i.e., confounding specific to ecological studies), which occurswhen relationships for groups are also true for individuals, is missing in the Limitation section.The authors have rightly applied multiple linear regression (MLR) analysis to overcome theconfounding. It would be far better if they applied the multilevel modelling (MLM) techniques,which overcome the ecological fallacy even better and help examine the contextual effects.*Lines 149-150: Cite the references to those previous studies.*Lines 151-153: How could you confirm this? Did you extensively search for the information inthe literature?*Lines 158-160: This information seems irrelevant for the present study. Also, clarify whether theinformation from these references have any connection or relation with the topic.*Lines 170-172: Rewrite the sentence clearly.
Conclusion, Lines 184-185: How did you confirm that that this was the first ecological study of
drugs used to alleviate constipation in the Japanese population? Did you extensively search theliterature?Abbreviations: You may remove most of the well-known abbreviations from the list. This will
save space.
Tables 4-7: Clarify why you did not keep the same predictors for the MLR analysis. If you did so,
it would be easier to compare the results or outputs. It would also make it easy to merge the tablesinto one composite table with different outcomes with the same predictors.
Publons Reviewer Recognition. Springer Nature can send verification of this review directly to
Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service,please click on the “Yes” option below. Your name, email address, title of the reviewed
manuscript, name of the journal, and date of your review submission (the “Review Data”) will
then be transmitted to Publons upon publication of the manuscript. If you have already registeredat Publons, they will notify you of the receipt of this review and update your profile as per yoursettings and their policy. If you are not registered with Publons, you will receive an email fromthem asking you to register in order for them to be able to recognize your review on your newprofile page. Publons may use the Review Data to generate derivative metadata for the benefit ofPublons and you as a reviewer, carefully considering the sensitivity of such information. Forexample, Publons may verify your record as a reviewer by updating your profile published on itswebservice if you have registered for such service or help editors to identify candidate reviewers.
Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms
No
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
NoDoes the work include the necessary controls?
If not, please specify which controls are required in your comments to the authors.
No
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
NoAre you able to assess any statistics in the manuscript or would you recommend an
additional statistical review?If an additional statistical review is recommended, please specify what aspects require furtherassessment in your comments to the editors.
I am able to assess the statisticsQuality of written English
Please indicate the quality of language in the manuscript:
Needs some language corrections before being published
Declaration of competing interests
Please complete a declaration of competing interests, considering the following questions:
1. Have you in the past five years received reimbursements, fees, funding, or salary from an
organisation that may in any way gain or lose financially from the publication of thismanuscript, either now or in the future?
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose
financially from the publication of this manuscript, either now or in the future?
3. Do you hold or are you currently applying for any patents relating to the content of the
manuscript?
4. Have you received reimbursements, fees, funding, or salary from an organization that holds
or has applied for patents relating to the content of the manuscript?
5. Do you have any other financial competing interests?
6. Do you have any non-financial competing interests in relation to this paper?
If you can answer no to all of the above, write 'I declare that I have no competing interests' below.
If your reply is yes to any, please give details below.
This reviewer has been recruited by a partner organization, Research Square. Reviewers with
declared or apparent competing interests are not utilized for these reviews. This reviewer hasagreed to publication of their comments online under a Creative Commons Attribution Licenseattributed to Research Square and was paid a small honorarium for completing the review within a
specified timeframe. Honoraria for reviews such as this are paid regardless of the reviewer
recommendation.
Reviewer Publication Consent. I agree for my report to be made available under an Open Access
Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manu-script is accepted for publication. Any comments that I do not wish to be included in the publishedreport have been included as confidential comments to the editor, which will not be published.Ifyou are not happy for us to publish this report, please contact the editorial office before completingthe review.If you wish, you can include your name in your published report. Please note you mustdecide whether to include your name at the start of the process and confirm this decision wheneverprompted. If you change your decision later, we will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report.
(default)
Please review this paper.
user
Reviewer’ s report
Title: Factors correlated with drug use for constipation: perspectives from the 2016 open Japanese
National Database
Version: 0Date: 23 Jun 2020
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research
question(s) (brief or other article types: is there a clear objective)?Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for the
objective?Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with technical rigor to allow
confidence in the results?No - there are minor issues
STATISTICS - Is the use of statistics in the manuscript appropriate?
No - there are issues with the statistics in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically sound?
If not, can revisions be made to make the work technically sound?Probably - with minor revisions
PEER REVIEWER COMMENTS:GENERAL COMMENTS:
The authors have investigated the risk factors for constipation drug use using the open JapaneseNational Database (NDB). Lots of researches have been done using the NDB since it was publiclyreleased to researchers in 2011. Few of them were conducted by Yonekura (2019); Shinichiro et al.(2018); and Hirose et al. (2020). The authors have also claimed that this was the first ecologicalstudy of drugs used to alleviate constipation in the Japanese population. This will help the clinicalpractitioners consider the risk factors while managing constipation.
The authors have used the data from the open Japanese National Database (NDB) and have
applied ecologic study to make large-scale comparisons among the 47 cities in Japan (as indicated
in the supplementary file). They have analyzed the data with multiple linear regression (MLR).
This helped minimize the impact of the confounding for the ecological fallacy, which is inherent incase of ecologic studies.
The authors have to show the associated F-values and coefficient of determination (R2) values
while applying the MLR analysis. It would be far better if they applied the multilevel modelling(MLM) techniques, which would overcome the ecological fallacy even better and help examinethe contextual effects.
REQUESTED REVISIONS:
The authors are suggested to clarify the issues related to the alternative statistical analysis andstrategy to minimize the inherent ecological fallacy.ADDITIONAL REQUESTS/SUGGESTIONS:General comments:*Keep 'stimulant laxatives' instead of 'stimulative laxatives' in table 5 and figure 2.*Keep figure labelling in figures 1 and 2.
Specific comments:
Title: You may reformat the title in the compounding or hanging style such as "Factors correlatingwith drug use for constipation: perspective/evaluation/analysis from the 2016 open JapaneseNational Database" or something like this, to make the title more attractive. You may think on it, ifyou find it alright.
Background:
*Lines 55-57: Specify the country where the prevalence was the lowest (i.e., 2%) and where it wasthe highest (i.e., 27%).*Lines 65-66: Cite the reference where it was reported.
Methods:
*It will be better if you rewrite Methods section under relevant subheadings such as study type,data source (for this secondary data source), data extraction, inclusion and exclusion criteria,sampling technique employed, statistical analysis and other.*Lines 82-84: Give examples of each category.*It would be better if the authors presented the background information to NDB along with themodality of getting access to the NDB in the Methods section of the present research. Thefollowing reference may help you in this direction:Hirose N, Ishimaru M, Morita K, Yasunaga H. A review of studies using the Japanese NationalDatabase of Health Insurance Claims and Specific Health Checkups. Annals of ClinicalEpidemiology 2020;2(1):13-26.It's just a suggestion; you may keep the abovementioned information related to NDB from otherresearches as well.
Results:
*Lines 104-105: Since your topic deals with constipation and lactulose can be used forconstipation, you have excluded lactulose from your study. Clarify the reason for its exclusion.
This also applies for the lines 177-178 in the Discussion section.
*Lines 135-136: How could you confirm that only aging was the independent risk factor? Didn't
other risk factors influence magnesium laxatives/purgatives?
Discussion:
*Lines 148-149: You have mentioned that you have reported the results of an ecological analysisof health insurance claims (prescriptions) for the alleviation of constipation. Mention this studydesign in the Methods section as well. Since ecological (ecologic) studies (also known as analysesof secular trends) help analyze data from a single region and examine how the trend changes overtime, or analyze data from a single time period and compare how the data differ from region to
region or country to country, such study design seems relevant here. Here, you have presented the
comparative view of 47 cities in the supplementary Excel file. However, discussion of the inherentproblem of the ecological fallacy (i.e., confounding specific to ecological studies), which occurswhen relationships for groups are also true for individuals, is missing in the Limitation section.The authors have rightly applied multiple linear regression (MLR) analysis to overcome theconfounding. It would be far better if they applied the multilevel modelling (MLM) techniques,which overcome the ecological fallacy even better and help examine the contextual effects.*Lines 149-150: Cite the references to those previous studies.*Lines 151-153: How could you confirm this? Did you extensively search for the information inthe literature?*Lines 158-160: This information seems irrelevant for the present study. Also, clarify whether theinformation from these references have any connection or relation with the topic.*Lines 170-172: Rewrite the sentence clearly.
Conclusion, Lines 184-185: How did you confirm that that this was the first ecological study of
drugs used to alleviate constipation in the Japanese population? Did you extensively search theliterature?Abbreviations: You may remove most of the well-known abbreviations from the list. This will
save space.
Tables 4-7: Clarify why you did not keep the same predictors for the MLR analysis. If you did so,
it would be easier to compare the results or outputs. It would also make it easy to merge the tablesinto one composite table with different outcomes with the same predictors.
Publons Reviewer Recognition. Springer Nature can send verification of this review directly to
Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service,please click on the “Yes” option below. Your name, email address, title of the reviewed
manuscript, name of the journal, and date of your review submission (the “Review Data”) will
then be transmitted to Publons upon publication of the manuscript. If you have already registeredat Publons, they will notify you of the receipt of this review and update your profile as per yoursettings and their policy. If you are not registered with Publons, you will receive an email fromthem asking you to register in order for them to be able to recognize your review on your newprofile page. Publons may use the Review Data to generate derivative metadata for the benefit ofPublons and you as a reviewer, carefully considering the sensitivity of such information. Forexample, Publons may verify your record as a reviewer by updating your profile published on itswebservice if you have registered for such service or help editors to identify candidate reviewers.
Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms
No
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
NoDoes the work include the necessary controls?
If not, please specify which controls are required in your comments to the authors.
No
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
NoAre you able to assess any statistics in the manuscript or would you recommend an
additional statistical review?If an additional statistical review is recommended, please specify what aspects require furtherassessment in your comments to the editors.
I am able to assess the statisticsQuality of written English
Please indicate the quality of language in the manuscript:
Needs some language corrections before being published
Declaration of competing interests
Please complete a declaration of competing interests, considering the following questions:
1. Have you in the past five years received reimbursements, fees, funding, or salary from an
organisation that may in any way gain or lose financially from the publication of thismanuscript, either now or in the future?
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose
financially from the publication of this manuscript, either now or in the future?
3. Do you hold or are you currently applying for any patents relating to the content of the
manuscript?
4. Have you received reimbursements, fees, funding, or salary from an organization that holds
or has applied for patents relating to the content of the manuscript?
5. Do you have any other financial competing interests?
6. Do you have any non-financial competing interests in relation to this paper?
If you can answer no to all of the above, write 'I declare that I have no competing interests' below.
If your reply is yes to any, please give details below.
This reviewer has been recruited by a partner organization, Research Square. Reviewers with
declared or apparent competing interests are not utilized for these reviews. This reviewer hasagreed to publication of their comments online under a Creative Commons Attribution Licenseattributed to Research Square and was paid a small honorarium for completing the review within a
specified timeframe. Honoraria for reviews such as this are paid regardless of the reviewer
recommendation.
Reviewer Publication Consent. I agree for my report to be made available under an Open Access
Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manu-script is accepted for publication. Any comments that I do not wish to be included in the publishedreport have been included as confidential comments to the editor, which will not be published.Ifyou are not happy for us to publish this report, please contact the editorial office before completingthe review.If you wish, you can include your name in your published report. Please note you mustdecide whether to include your name at the start of the process and confirm this decision wheneverprompted. If you change your decision later, we will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report.
(default)
assistant