Reviewer ’s report  
 
Title: Discounting the Duration of Bolus Exposure in Impedance Tes ting Underestimates Acid 
Reflux  
 
 
Version: 0 Date: 09 Dec 2015  
 
 
Reviewer: Wai-Kit Lo 
 
 
Reviewer's report:  
 
In this study, t he authors compared the use of impedance versus pH -only parameters in the 
diagnosis of acid reflux, and found that acid exposure on pH testing demonstrated abnormal 
results more often than bolus episodes on impedance.  They conclude that impedance testing 
may therefore underestimate pathologic acid reflux.  
 
Introduction:  
Page 6, Lines 13 -16: This statement is not supported by the citations.  In impedance testing, a 
threshold of 1.4% has been established as the 95th percentile for bolus exposure (and 1.1% as the 
cutoff for acid exposure), in diagnosing the presence of patho logic reflux. This is equivalent to 
the measured cutoff of 4.2% for pathologic acid exposure in pH -only data.  Please clarify the 
statement.  
 
Page 6, Line 22: Consequent to the above response, impedance testing does _not_ discount the 
duration of bolus expo sure in the determination of pathologic reflux.  In clinical practice, bolus 
exposure >1.4% (and acid exposure >1.1%) on impedance testing should be counted as 
pathologic reflux, and thus, a positive study.  
 
Additionally , a positive Demeester is not the onl y determinant of a positive pH study, so the 
criteria used by the authors should be clearly delineated.  
 
Methods:  
Page 8, Lines 16 -22: Were bolus exposures based on impedance not calculated or analyzed?  The 
Sandhill analysis package should calculate imped ance-based bolus exposures as part of routine 
study interpretation.  Please clarify.  
 
Results:  
Page 10, Lines 4 -5: Please explicitly state which criteria were used to determine an abnormal 
study based on pH and impedance parameters.  
 
Page 10, Lines 10 -11: I believe there is a critical flaw in this study, in that only impedance based 
reflux episode activity was used to assess for pathologic reflux, without any consideration of 
impedance based bolus exposures.  Table 1 does not include any data on impedance -based bolus 
exposures.  
 
Discussion:  
The authors do an admirable job of discussing the lack of sensitivity when assessing reflux 
episodes on impedance testing compared to acid exposure on pH testing in determining 
pathologic reflux.  This conclusion cannot be  disputed; however, bolus exposure impedance data 
is readily available in the Sandhill data analysis software package, are routinely considered in the 
interpretation of impedance test results, and have not been taken into consideration here.  A more 
intere sting study would be to compare the acid exposure pH data and bolus exposure impedance 
data in determining pathologic reflux.  As it stands, the study represents an incomplete use of 
current impedance testing methods.  
 
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 adequately 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 recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the ma nuscript:  
 
Acceptable  
 
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 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 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 com peting 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.  
 
I declare that I have no competing interests'  
 
I agree t o 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 named 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: Discounting the Duration of Bolus Exposure in Impedance Tes ting Underestimates Acid 
Reflux  
 
 
Version: 0 Date: 09 Dec 2015  
 
 
Reviewer: Wai-Kit Lo 
 
 
Reviewer's report:  
 
In this study, t he authors compared the use of impedance versus pH -only parameters in the 
diagnosis of acid reflux, and found that acid exposure on pH testing demonstrated abnormal 
results more often than bolus episodes on impedance.  They conclude that impedance testing 
may therefore underestimate pathologic acid reflux.  
 
Introduction:  
Page 6, Lines 13 -16: This statement is not supported by the citations.  In impedance testing, a 
threshold of 1.4% has been established as the 95th percentile for bolus exposure (and 1.1% as the 
cutoff for acid exposure), in diagnosing the presence of patho logic reflux. This is equivalent to 
the measured cutoff of 4.2% for pathologic acid exposure in pH -only data.  Please clarify the 
statement.  
 
Page 6, Line 22: Consequent to the above response, impedance testing does _not_ discount the 
duration of bolus expo sure in the determination of pathologic reflux.  In clinical practice, bolus 
exposure >1.4% (and acid exposure >1.1%) on impedance testing should be counted as 
pathologic reflux, and thus, a positive study.  
 
Additionally , a positive Demeester is not the onl y determinant of a positive pH study, so the 
criteria used by the authors should be clearly delineated.  
 
Methods:  
Page 8, Lines 16 -22: Were bolus exposures based on impedance not calculated or analyzed?  The 
Sandhill analysis package should calculate imped ance-based bolus exposures as part of routine 
study interpretation.  Please clarify.  
 
Results:  
Page 10, Lines 4 -5: Please explicitly state which criteria were used to determine an abnormal 
study based on pH and impedance parameters.  
 
Page 10, Lines 10 -11: I believe there is a critical flaw in this study, in that only impedance based 
reflux episode activity was used to assess for pathologic reflux, without any consideration of 
impedance based bolus exposures.  Table 1 does not include any data on impedance -based bolus 
exposures.  
 
Discussion:  
The authors do an admirable job of discussing the lack of sensitivity when assessing reflux 
episodes on impedance testing compared to acid exposure on pH testing in determining 
pathologic reflux.  This conclusion cannot be  disputed; however, bolus exposure impedance data 
is readily available in the Sandhill data analysis software package, are routinely considered in the 
interpretation of impedance test results, and have not been taken into consideration here.  A more 
intere sting study would be to compare the acid exposure pH data and bolus exposure impedance 
data in determining pathologic reflux.  As it stands, the study represents an incomplete use of 
current impedance testing methods.  
 
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 adequately 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 recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the ma nuscript:  
 
Acceptable  
 
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 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 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 com peting 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.  
 
I declare that I have no competing interests'  
 
I agree t o 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 named 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: Discounting the Duration of Bolus Exposure in Impedance Tes ting Underestimates Acid 
Reflux  
 
 
Version: 0 Date: 09 Dec 2015  
 
 
Reviewer: Wai-Kit Lo 
 
 
Reviewer's report:  
 
In this study, t he authors compared the use of impedance versus pH -only parameters in the 
diagnosis of acid reflux, and found that acid exposure on pH testing demonstrated abnormal 
results more often than bolus episodes on impedance.  They conclude that impedance testing 
may therefore underestimate pathologic acid reflux.  
 
Introduction:  
Page 6, Lines 13 -16: This statement is not supported by the citations.  In impedance testing, a 
threshold of 1.4% has been established as the 95th percentile for bolus exposure (and 1.1% as the 
cutoff for acid exposure), in diagnosing the presence of patho logic reflux. This is equivalent to 
the measured cutoff of 4.2% for pathologic acid exposure in pH -only data.  Please clarify the 
statement.  
 
Page 6, Line 22: Consequent to the above response, impedance testing does _not_ discount the 
duration of bolus expo sure in the determination of pathologic reflux.  In clinical practice, bolus 
exposure >1.4% (and acid exposure >1.1%) on impedance testing should be counted as 
pathologic reflux, and thus, a positive study.  
 
Additionally , a positive Demeester is not the onl y determinant of a positive pH study, so the 
criteria used by the authors should be clearly delineated.  
 
Methods:  
Page 8, Lines 16 -22: Were bolus exposures based on impedance not calculated or analyzed?  The 
Sandhill analysis package should calculate imped ance-based bolus exposures as part of routine 
study interpretation.  Please clarify.  
 
Results:  
Page 10, Lines 4 -5: Please explicitly state which criteria were used to determine an abnormal 
study based on pH and impedance parameters.  
 
Page 10, Lines 10 -11: I believe there is a critical flaw in this study, in that only impedance based 
reflux episode activity was used to assess for pathologic reflux, without any consideration of 
impedance based bolus exposures.  Table 1 does not include any data on impedance -based bolus 
exposures.  
 
Discussion:  
The authors do an admirable job of discussing the lack of sensitivity when assessing reflux 
episodes on impedance testing compared to acid exposure on pH testing in determining 
pathologic reflux.  This conclusion cannot be  disputed; however, bolus exposure impedance data 
is readily available in the Sandhill data analysis software package, are routinely considered in the 
interpretation of impedance test results, and have not been taken into consideration here.  A more 
intere sting study would be to compare the acid exposure pH data and bolus exposure impedance 
data in determining pathologic reflux.  As it stands, the study represents an incomplete use of 
current impedance testing methods.  
 
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 adequately 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 recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the ma nuscript:  
 
Acceptable  
 
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 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 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 com peting 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.  
 
I declare that I have no competing interests'  
 
I agree t o 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 named 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