Reviewer’s report
Title: Gastroesophageal reflux disease in a typical African population A symptom-based multicenter
study.
Version: 1 Date: 25 May 2019
Reviewer: Helena Nordenstedt
Reviewer's report:
This is an ambitious attempt by the authors to study the prevalence and associated risk factors of
GERD in Nigeria. There is a major gap in GERD research, with little or no population prevalence data
from the African continent, especially from the Sub-Saharan setting. The present study is therefore a
welcome addition and the authors to be complimented for their ambitious attempt. However, from the
manuscript, it is not possible to know if the current study is population-based or not, since the selection
of participants has not been described in detail. In general, the methods section needs to be expanded
substantially in order for the reader to be able to fully understand how the study was carried out.
MAJOR COMMENTS:
-Please describe how the selection of individuals participating in the study was done. (It is
described down to cluster level, but not further). Was it based on households? Which households then,
and which members of the household?
-Did everyone who was approached agree to participate? Or how many declined? 
-Please add the specific definitions used for GERD, EPS, PDS and IBS. 
-I would recommend adding more into  the  discussion about how  the results  of this  study
compare to results from other studies from the Sub-Saharan setting, putting it into context for those
unfamiliar with the setting (and less about how the different disease entities relate and overlap).
-I also do not agree that it is an "obvious limitation" that endoscopy and functional reflux testing
were not done. Some of the landmark studies increasing our understanding about GERD have been
symptom-based.
-Was the questionnaire translated into local languages?
-Please also discuss the validity of using tools developed in high-income settings for a setting
like Nigeria. Has there been any qualitative study looking into how Nigerians perceive these questions,
and could it be that they differ in different parts of the country, depending on translation of the
questionnaire? (This could possibly explain the difference in prevalence seen between the regions for
some of the symptoms, but not others.)
-The lack of symptoms in the North East (except heartburn and regurgitations) is quite striking
and needs to be discussed.
-How were the covariates included in the logistical regression chosen? 
-Most  potential  risk  factors  are  missing  from table  4,  where  only age  and  occupation  are
included. It would seem pertinent to at least include BMI, and smoking if available in the analyses. 
-Please add to the methods the classification of the covariates. In table 4, also indicate what was
chosen as the reference level.
MINOR COMMENTS:
General: 
Please be consistent in use of number of decimals. (See abstract for instance, and I would recommend
using 1 decimal, but that might be personal preference.)
Page 2 (Abstract)
Row 27: I would recommend exchanging the sentence about what software was used (not so interesting
detail for an abstract), to how the selection of participants was made.
Page 3
Row 15: Please change "into the esophagus, up to the mouth and lungs" into "into the esophagus, up to
the mouth and possibly lungs" to clarify that not all GERD patients have respiratory symptoms.
Row 25: Even though a symptom-based diagnosis has its disadvantage, it is well-known that symptoms
only strongly increase the risk of esophageal adenocarcinoma (Lagergren et al, NEJM 1999). I would
therefore suggest adding this.
Row 44: When discussing the share of the population suffering from GERD, please add if this is in
adult populations, and what the definition is (i.e. symptoms at least weekly? monthly?)
Row 51: In the Chinese and Greek studies referred, was the same definition used? Please clarify.
Page 4:
Row 4: Please add reference to the statement of BE and esophageal carcinoma as well as decreased
work productivity.
Row 28 and 33: It doesn't really add to the background knowing the exact decimals of the surface of
Nigeria. Also saying "about" and then giving an exact number of the population also seems a bit
misleading. Please round the numbers for better understanding.
Page 5
Row 30: If this formula is to be kept (normally the sample size calculation is not presented in this
detail, then please also add the estimated prevalence of GERD. (Was it the same prevalence estimated
for all project areas? Please clarify.)
Page 7
Row 35: Please add also mean age for participants without GERD for comparison.
Row 47: Please clarify the sentence "Other associated symptoms were xx xx%, xx xx%". Associated in
what way? Was this prevalence in the whole population or those with GERD?
Page 9
Row 38: potable instead of portable
Row  43:  I  would  not  agree  that  epidemiological  studies  have  consistently  showed  an  inverse
relationship between Hp infection and GERD. (For instance, see the results from the population-based
HUNT study in Norway by myself and colleagues, Nordenstedt et al, Helicobacter, 2007). 
Page 11
The discussion on physical activity would need some more nuance. Regular physical activity has been
shown to be protective against GERD (Zheng et al, Gastroenterology 2008 for example). However,
single strenuous events, like weight-lifting, can trigger an episode of reflux, but not increase the long-
term risk of GERD.
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.
Unable to assess
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
Unable to assess
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 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 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 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.
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 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: Gastroesophageal reflux disease in a typical African population A symptom-based multicenter
study.
Version: 1 Date: 25 May 2019
Reviewer: Helena Nordenstedt
Reviewer's report:
This is an ambitious attempt by the authors to study the prevalence and associated risk factors of
GERD in Nigeria. There is a major gap in GERD research, with little or no population prevalence data
from the African continent, especially from the Sub-Saharan setting. The present study is therefore a
welcome addition and the authors to be complimented for their ambitious attempt. However, from the
manuscript, it is not possible to know if the current study is population-based or not, since the selection
of participants has not been described in detail. In general, the methods section needs to be expanded
substantially in order for the reader to be able to fully understand how the study was carried out.
MAJOR COMMENTS:
-Please describe how the selection of individuals participating in the study was done. (It is
described down to cluster level, but not further). Was it based on households? Which households then,
and which members of the household?
-Did everyone who was approached agree to participate? Or how many declined? 
-Please add the specific definitions used for GERD, EPS, PDS and IBS. 
-I would recommend adding more into  the  discussion about how  the results  of this  study
compare to results from other studies from the Sub-Saharan setting, putting it into context for those
unfamiliar with the setting (and less about how the different disease entities relate and overlap).
-I also do not agree that it is an "obvious limitation" that endoscopy and functional reflux testing
were not done. Some of the landmark studies increasing our understanding about GERD have been
symptom-based.
-Was the questionnaire translated into local languages?
-Please also discuss the validity of using tools developed in high-income settings for a setting
like Nigeria. Has there been any qualitative study looking into how Nigerians perceive these questions,
and could it be that they differ in different parts of the country, depending on translation of the
questionnaire? (This could possibly explain the difference in prevalence seen between the regions for
some of the symptoms, but not others.)
-The lack of symptoms in the North East (except heartburn and regurgitations) is quite striking
and needs to be discussed.
-How were the covariates included in the logistical regression chosen? 
-Most  potential  risk  factors  are  missing  from table  4,  where  only age  and  occupation  are
included. It would seem pertinent to at least include BMI, and smoking if available in the analyses. 
-Please add to the methods the classification of the covariates. In table 4, also indicate what was
chosen as the reference level.
MINOR COMMENTS:
General: 
Please be consistent in use of number of decimals. (See abstract for instance, and I would recommend
using 1 decimal, but that might be personal preference.)
Page 2 (Abstract)
Row 27: I would recommend exchanging the sentence about what software was used (not so interesting
detail for an abstract), to how the selection of participants was made.
Page 3
Row 15: Please change "into the esophagus, up to the mouth and lungs" into "into the esophagus, up to
the mouth and possibly lungs" to clarify that not all GERD patients have respiratory symptoms.
Row 25: Even though a symptom-based diagnosis has its disadvantage, it is well-known that symptoms
only strongly increase the risk of esophageal adenocarcinoma (Lagergren et al, NEJM 1999). I would
therefore suggest adding this.
Row 44: When discussing the share of the population suffering from GERD, please add if this is in
adult populations, and what the definition is (i.e. symptoms at least weekly? monthly?)
Row 51: In the Chinese and Greek studies referred, was the same definition used? Please clarify.
Page 4:
Row 4: Please add reference to the statement of BE and esophageal carcinoma as well as decreased
work productivity.
Row 28 and 33: It doesn't really add to the background knowing the exact decimals of the surface of
Nigeria. Also saying "about" and then giving an exact number of the population also seems a bit
misleading. Please round the numbers for better understanding.
Page 5
Row 30: If this formula is to be kept (normally the sample size calculation is not presented in this
detail, then please also add the estimated prevalence of GERD. (Was it the same prevalence estimated
for all project areas? Please clarify.)
Page 7
Row 35: Please add also mean age for participants without GERD for comparison.
Row 47: Please clarify the sentence "Other associated symptoms were xx xx%, xx xx%". Associated in
what way? Was this prevalence in the whole population or those with GERD?
Page 9
Row 38: potable instead of portable
Row  43:  I  would  not  agree  that  epidemiological  studies  have  consistently  showed  an  inverse
relationship between Hp infection and GERD. (For instance, see the results from the population-based
HUNT study in Norway by myself and colleagues, Nordenstedt et al, Helicobacter, 2007). 
Page 11
The discussion on physical activity would need some more nuance. Regular physical activity has been
shown to be protective against GERD (Zheng et al, Gastroenterology 2008 for example). However,
single strenuous events, like weight-lifting, can trigger an episode of reflux, but not increase the long-
term risk of GERD.
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.
Unable to assess
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
Unable to assess
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 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 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 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.
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 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: Gastroesophageal reflux disease in a typical African population A symptom-based multicenter
study.
Version: 1 Date: 25 May 2019
Reviewer: Helena Nordenstedt
Reviewer's report:
This is an ambitious attempt by the authors to study the prevalence and associated risk factors of
GERD in Nigeria. There is a major gap in GERD research, with little or no population prevalence data
from the African continent, especially from the Sub-Saharan setting. The present study is therefore a
welcome addition and the authors to be complimented for their ambitious attempt. However, from the
manuscript, it is not possible to know if the current study is population-based or not, since the selection
of participants has not been described in detail. In general, the methods section needs to be expanded
substantially in order for the reader to be able to fully understand how the study was carried out.
MAJOR COMMENTS:
-Please describe how the selection of individuals participating in the study was done. (It is
described down to cluster level, but not further). Was it based on households? Which households then,
and which members of the household?
-Did everyone who was approached agree to participate? Or how many declined? 
-Please add the specific definitions used for GERD, EPS, PDS and IBS. 
-I would recommend adding more into  the  discussion about how  the results  of this  study
compare to results from other studies from the Sub-Saharan setting, putting it into context for those
unfamiliar with the setting (and less about how the different disease entities relate and overlap).
-I also do not agree that it is an "obvious limitation" that endoscopy and functional reflux testing
were not done. Some of the landmark studies increasing our understanding about GERD have been
symptom-based.
-Was the questionnaire translated into local languages?
-Please also discuss the validity of using tools developed in high-income settings for a setting
like Nigeria. Has there been any qualitative study looking into how Nigerians perceive these questions,
and could it be that they differ in different parts of the country, depending on translation of the
questionnaire? (This could possibly explain the difference in prevalence seen between the regions for
some of the symptoms, but not others.)
-The lack of symptoms in the North East (except heartburn and regurgitations) is quite striking
and needs to be discussed.
-How were the covariates included in the logistical regression chosen? 
-Most  potential  risk  factors  are  missing  from table  4,  where  only age  and  occupation  are
included. It would seem pertinent to at least include BMI, and smoking if available in the analyses. 
-Please add to the methods the classification of the covariates. In table 4, also indicate what was
chosen as the reference level.
MINOR COMMENTS:
General: 
Please be consistent in use of number of decimals. (See abstract for instance, and I would recommend
using 1 decimal, but that might be personal preference.)
Page 2 (Abstract)
Row 27: I would recommend exchanging the sentence about what software was used (not so interesting
detail for an abstract), to how the selection of participants was made.
Page 3
Row 15: Please change "into the esophagus, up to the mouth and lungs" into "into the esophagus, up to
the mouth and possibly lungs" to clarify that not all GERD patients have respiratory symptoms.
Row 25: Even though a symptom-based diagnosis has its disadvantage, it is well-known that symptoms
only strongly increase the risk of esophageal adenocarcinoma (Lagergren et al, NEJM 1999). I would
therefore suggest adding this.
Row 44: When discussing the share of the population suffering from GERD, please add if this is in
adult populations, and what the definition is (i.e. symptoms at least weekly? monthly?)
Row 51: In the Chinese and Greek studies referred, was the same definition used? Please clarify.
Page 4:
Row 4: Please add reference to the statement of BE and esophageal carcinoma as well as decreased
work productivity.
Row 28 and 33: It doesn't really add to the background knowing the exact decimals of the surface of
Nigeria. Also saying "about" and then giving an exact number of the population also seems a bit
misleading. Please round the numbers for better understanding.
Page 5
Row 30: If this formula is to be kept (normally the sample size calculation is not presented in this
detail, then please also add the estimated prevalence of GERD. (Was it the same prevalence estimated
for all project areas? Please clarify.)
Page 7
Row 35: Please add also mean age for participants without GERD for comparison.
Row 47: Please clarify the sentence "Other associated symptoms were xx xx%, xx xx%". Associated in
what way? Was this prevalence in the whole population or those with GERD?
Page 9
Row 38: potable instead of portable
Row  43:  I  would  not  agree  that  epidemiological  studies  have  consistently  showed  an  inverse
relationship between Hp infection and GERD. (For instance, see the results from the population-based
HUNT study in Norway by myself and colleagues, Nordenstedt et al, Helicobacter, 2007). 
Page 11
The discussion on physical activity would need some more nuance. Regular physical activity has been
shown to be protective against GERD (Zheng et al, Gastroenterology 2008 for example). However,
single strenuous events, like weight-lifting, can trigger an episode of reflux, but not increase the long-
term risk of GERD.
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.
Unable to assess
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
Unable to assess
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 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 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 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.
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 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