Reviewer ’s report  
Title: Sex and Ethnic/Racial -specific Risk Factors for Gall bladder Disease  
 
Version: 0 Date: 26 Sep 2016  
 
Reviewer: Somashekar Krishna  
 
Reviewer's report:  
Overall, the manuscript presents a prospective analysis from multiethnic US populations and the 
risk of GBD based on exposure levels of various risk factors across gender and racial groups.  
 
Abstract:  
It appears that this is a matched analysis. If so, it is important to mention this in the abstract.  
 
Background, paragraph 1:  
I am not sure about the importance of mentioning the risk of cholecystectomy (CCY) and 
increased risk of extra hepatic bile tract, stomach, liver and pancreas cancers.  
 
Although not absolutely necessary, a study flow chart (inclusion, exclusion, missing, final study 
population, statistical method used) would help the reader significantly.  
 
GBD Case identification: If all CCYs were included, does this include those CCYs without 
gallstones as well? Some CCYs are performed without a finding of GBD (either during other 
hepatobiliary/pancreatic surgeries or in suspected stone disease). Would a sens itivity analysis 
benefit this to know the proportion of patients? If performed, supplemental data would be of 
help.  
 
Statistical analysis: This is a matched analysis. What was the ratio of matching (if applicable) 
case: control. The methods are a bit diff icult to follow - so the cases were matched with controls 
and a risk of association between the exposure and the outcome (GBD) was calculated. Were 
these risks adjusted for potential confounders.  
If Cox modeling were used to determine risks - then hazards  ratios and 95 % confidence intervals 
from multivariable Cox proportional hazards models are required. It is not sure if matching alone 
would sufficiently negate the benefits of a multivariate analysis.  
 
Tables 2 through 5: There is a significant amount o f data. It appears that these are all univariate 
associations. It is not clear if multivariate analyses (adjusting for each variable and the 
interactions within) were performed. The authors need to explain as to why multivariate analyses 
(adjusting for con founders) is not needed. I am not sure that just matching cases and control 
suffices.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
No 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
Yes 
Are the conclusions drawn adequa tely supported by the data shown?  
If not, please explain in your comments to the authors.  
Yes 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommende d, please specify what aspects require further  
assessment in your comments to the editors.  
I recommend additional statistical review  
Quality of written English  
Please indicate the quality of language in the manuscript:  
Acceptable  
Declaration of competing interest s 
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 pub lication of this  
manuscript, 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 cu rrently 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 an y, please give details below.  
 
I declare that I have no competing interests  
 
I agree to the open peer review policy of the journal. I understand that my name will be included 
on my report to the authors and, if the manuscript is accepted for publication, my n amed report 
including any attachments I upload will be posted on the website along with the authors' 
responses. 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/ ). I understand that any comments 
which I do not wish to be included in my named report can be included as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
Title: Sex and Ethnic/Racial -specific Risk Factors for Gall bladder Disease  
 
Version: 0 Date: 26 Sep 2016  
 
Reviewer: Somashekar Krishna  
 
Reviewer's report:  
Overall, the manuscript presents a prospective analysis from multiethnic US populations and the 
risk of GBD based on exposure levels of various risk factors across gender and racial groups.  
 
Abstract:  
It appears that this is a matched analysis. If so, it is important to mention this in the abstract.  
 
Background, paragraph 1:  
I am not sure about the importance of mentioning the risk of cholecystectomy (CCY) and 
increased risk of extra hepatic bile tract, stomach, liver and pancreas cancers.  
 
Although not absolutely necessary, a study flow chart (inclusion, exclusion, missing, final study 
population, statistical method used) would help the reader significantly.  
 
GBD Case identification: If all CCYs were included, does this include those CCYs without 
gallstones as well? Some CCYs are performed without a finding of GBD (either during other 
hepatobiliary/pancreatic surgeries or in suspected stone disease). Would a sens itivity analysis 
benefit this to know the proportion of patients? If performed, supplemental data would be of 
help.  
 
Statistical analysis: This is a matched analysis. What was the ratio of matching (if applicable) 
case: control. The methods are a bit diff icult to follow - so the cases were matched with controls 
and a risk of association between the exposure and the outcome (GBD) was calculated. Were 
these risks adjusted for potential confounders.  
If Cox modeling were used to determine risks - then hazards  ratios and 95 % confidence intervals 
from multivariable Cox proportional hazards models are required. It is not sure if matching alone 
would sufficiently negate the benefits of a multivariate analysis.  
 
Tables 2 through 5: There is a significant amount o f data. It appears that these are all univariate 
associations. It is not clear if multivariate analyses (adjusting for each variable and the 
interactions within) were performed. The authors need to explain as to why multivariate analyses 
(adjusting for con founders) is not needed. I am not sure that just matching cases and control 
suffices.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
No 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
Yes 
Are the conclusions drawn adequa tely supported by the data shown?  
If not, please explain in your comments to the authors.  
Yes 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommende d, please specify what aspects require further  
assessment in your comments to the editors.  
I recommend additional statistical review  
Quality of written English  
Please indicate the quality of language in the manuscript:  
Acceptable  
Declaration of competing interest s 
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 pub lication of this  
manuscript, 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 cu rrently 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 an y, please give details below.  
 
I declare that I have no competing interests  
 
I agree to the open peer review policy of the journal. I understand that my name will be included 
on my report to the authors and, if the manuscript is accepted for publication, my n amed report 
including any attachments I upload will be posted on the website along with the authors' 
responses. 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/ ). I understand that any comments 
which I do not wish to be included in my named report can be included as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
Title: Sex and Ethnic/Racial -specific Risk Factors for Gall bladder Disease  
 
Version: 0 Date: 26 Sep 2016  
 
Reviewer: Somashekar Krishna  
 
Reviewer's report:  
Overall, the manuscript presents a prospective analysis from multiethnic US populations and the 
risk of GBD based on exposure levels of various risk factors across gender and racial groups.  
 
Abstract:  
It appears that this is a matched analysis. If so, it is important to mention this in the abstract.  
 
Background, paragraph 1:  
I am not sure about the importance of mentioning the risk of cholecystectomy (CCY) and 
increased risk of extra hepatic bile tract, stomach, liver and pancreas cancers.  
 
Although not absolutely necessary, a study flow chart (inclusion, exclusion, missing, final study 
population, statistical method used) would help the reader significantly.  
 
GBD Case identification: If all CCYs were included, does this include those CCYs without 
gallstones as well? Some CCYs are performed without a finding of GBD (either during other 
hepatobiliary/pancreatic surgeries or in suspected stone disease). Would a sens itivity analysis 
benefit this to know the proportion of patients? If performed, supplemental data would be of 
help.  
 
Statistical analysis: This is a matched analysis. What was the ratio of matching (if applicable) 
case: control. The methods are a bit diff icult to follow - so the cases were matched with controls 
and a risk of association between the exposure and the outcome (GBD) was calculated. Were 
these risks adjusted for potential confounders.  
If Cox modeling were used to determine risks - then hazards  ratios and 95 % confidence intervals 
from multivariable Cox proportional hazards models are required. It is not sure if matching alone 
would sufficiently negate the benefits of a multivariate analysis.  
 
Tables 2 through 5: There is a significant amount o f data. It appears that these are all univariate 
associations. It is not clear if multivariate analyses (adjusting for each variable and the 
interactions within) were performed. The authors need to explain as to why multivariate analyses 
(adjusting for con founders) is not needed. I am not sure that just matching cases and control 
suffices.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
No 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
Yes 
Are the conclusions drawn adequa tely supported by the data shown?  
If not, please explain in your comments to the authors.  
Yes 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommende d, please specify what aspects require further  
assessment in your comments to the editors.  
I recommend additional statistical review  
Quality of written English  
Please indicate the quality of language in the manuscript:  
Acceptable  
Declaration of competing interest s 
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 pub lication of this  
manuscript, 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 cu rrently 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 an y, please give details below.  
 
I declare that I have no competing interests  
 
I agree to the open peer review policy of the journal. I understand that my name will be included 
on my report to the authors and, if the manuscript is accepted for publication, my n amed report 
including any attachments I upload will be posted on the website along with the authors' 
responses. 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/ ). I understand that any comments 
which I do not wish to be included in my named report can be included as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant