Reviewer’s report
Title: The influence of demographic characteristics on constipation symptoms: A detailed overview
Version: 1 Date: 12 Sep 2019
Reviewer: Research Square Statistical Reviewer
Reviewer's report:
STATISTICAL REVIEWER ASSESSMENT: 
Is the study design appropriate for the research question (considering whether the analyzed population
accurately reflects the design and whether you see any problems with control/comparison groups, e.g.,
likely confounders)?
No - there are major issues
Are methodologies adequate and well implemented (considering whether assumptions are addressed
and whether analyses are robust)?
No - there are minor issues
Are the analyses adequately communicated (considering whether reporting details are adequate and
whether figures and tables are well labeled and described)?
No - there are major issues
Does the interpretation accurately reflect the analyses without overstatement (considering whether
limitations/bias are acknowledged and whether accurate descriptors, e.g., 'significant', are used?
No - there are minor issues
Could an appropriately REVISED version of this work represent a statistically sound contribution? 
Maybe - with major revisions
STATISTICAL REVIEWER COMMENTS:
This  was  an  interesting  study which  assessed  patients  self-reported  constipation  rates,  and  what
symptoms they had. The authors aimed to determine specific patterns of constipation symptoms in
different demographic groups, and to better define symptoms that best indicate functional constipation.
The statistical analysis was generally descriptive statistics, with proportions compared using chi-square
univariate analyses. Some changes are required to the multivariate regression analyses.
REQUESTED REVISIONS: 
Major comments:
1. Logistic regression - the authors tested for 'all assumptions'. However it was not clear whether
interaction terms were tested, or whether correlation/collinearity between covariates was assessed. It is
hard to believe there was no interaction between dietary factors and BMI, or at least these variables
should be correlated? If so, both should not be included in the same multivariable regression, or the
interaction term should be accounted for.
2. The authors used backward step-wise regression (using P-values, with P&lt;0.10) to determine which
confounders were included in multivariable models. This has been shown to be very inefficient and
may result in loss of important data (REF - Derksen &amp; Keselman, British Journal of Mathematical
and Statistical Psychology 1992; 45:265-282.)  Additionally, it relies on only statistical methods of
determining the best model, and not assessment of confounding based on evidence-based clinical
knowledge.  As such, the model developed is prone to the limits of the dataset and may not be
applicable to other studies.  A number of articles have suggested that the best models are constructed a
priori based on extensive review of the literature and expert opinion, and the model should then be
adjusted based on the c-statistic (REFS: Harrell et al., Stat Med 1996; 15:361-387, and Laupacis et al.,
JAMA 1997; 277:488-494).  Alternatively,  selecting including confounding variables  by the 10%
change in the Beta estimate method has been demonstrated better than step-wise selection (REF:
Greenland, Am J Epidemiol 2008; 167:523-529).
In fact, I think all variables could be included in the multivariable regression, assuming there is no
correlation between rural/urban and education level.  The study is powered to include 24+ degrees of
freedom (based on 247 patients with constipation), and only 11 degrees of freedom are currently used.
3. Figure 1 is not really observed:expected ratio graph. See the reference for O:E graphs in mortality:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5391699/  
I'm not really sure how you could conduct an observed:expected graph in your case. Your graph is more
the median observed events by age.
4.  Figures  2  demonstrates  the  large  number  of  comparisons  made,  reporting  P-values  for  each
comparison  (which  is  also  discussed  in  the  Results,  Lines  186-195).  Some  will  be  significant
(P&lt;0.05)  simply  by  chance.  Correction  for  multiple  testing  should  be  performed  (Tukey  or
Bonferroni).  
5. Figure 3 does not report standard deviations of the proportions seen, or the delta. The authors should
consider reporting this.
Non-statistical comments:
6. The authors should use the STROBE reporting guidelines to better report their study methods and
results. The methods used in data collection were not always well reported.
7. Where did the original 3031 respondents come from, and why did only 54.2% complete the survey?
Were these representative of the full group?
8. The authors have excluded a large proportion of the population who truly had constipation (anyone
with a medical history involving bowel functioning (proportion not reported), with a history of bowel
surgery (19.9%), somatic diseases influencing the bowel (proportion not reported), congenital disorders
(proportion not reported), medications with constipation as a side effect (9.3%), and other medications
that influence the bowel system (proportion not reported). This would eliminate a large number of
people  with  constipation,  and  29.2%  of  the  respondents,  and  therefore  their  cohort  may  not  be
representative of the typical population.
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.
No
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
No
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:
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 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  has  agreed  to
publication of their comments online under a Creative Commons Attribution License attributed 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.
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: The influence of demographic characteristics on constipation symptoms: A detailed overview
Version: 1 Date: 12 Sep 2019
Reviewer: Research Square Statistical Reviewer
Reviewer's report:
STATISTICAL REVIEWER ASSESSMENT: 
Is the study design appropriate for the research question (considering whether the analyzed population
accurately reflects the design and whether you see any problems with control/comparison groups, e.g.,
likely confounders)?
No - there are major issues
Are methodologies adequate and well implemented (considering whether assumptions are addressed
and whether analyses are robust)?
No - there are minor issues
Are the analyses adequately communicated (considering whether reporting details are adequate and
whether figures and tables are well labeled and described)?
No - there are major issues
Does the interpretation accurately reflect the analyses without overstatement (considering whether
limitations/bias are acknowledged and whether accurate descriptors, e.g., 'significant', are used?
No - there are minor issues
Could an appropriately REVISED version of this work represent a statistically sound contribution? 
Maybe - with major revisions
STATISTICAL REVIEWER COMMENTS:
This  was  an  interesting  study which  assessed  patients  self-reported  constipation  rates,  and  what
symptoms they had. The authors aimed to determine specific patterns of constipation symptoms in
different demographic groups, and to better define symptoms that best indicate functional constipation.
The statistical analysis was generally descriptive statistics, with proportions compared using chi-square
univariate analyses. Some changes are required to the multivariate regression analyses.
REQUESTED REVISIONS: 
Major comments:
1. Logistic regression - the authors tested for 'all assumptions'. However it was not clear whether
interaction terms were tested, or whether correlation/collinearity between covariates was assessed. It is
hard to believe there was no interaction between dietary factors and BMI, or at least these variables
should be correlated? If so, both should not be included in the same multivariable regression, or the
interaction term should be accounted for.
2. The authors used backward step-wise regression (using P-values, with P&lt;0.10) to determine which
confounders were included in multivariable models. This has been shown to be very inefficient and
may result in loss of important data (REF - Derksen &amp; Keselman, British Journal of Mathematical
and Statistical Psychology 1992; 45:265-282.)  Additionally, it relies on only statistical methods of
determining the best model, and not assessment of confounding based on evidence-based clinical
knowledge.  As such, the model developed is prone to the limits of the dataset and may not be
applicable to other studies.  A number of articles have suggested that the best models are constructed a
priori based on extensive review of the literature and expert opinion, and the model should then be
adjusted based on the c-statistic (REFS: Harrell et al., Stat Med 1996; 15:361-387, and Laupacis et al.,
JAMA 1997; 277:488-494).  Alternatively,  selecting including confounding variables  by the 10%
change in the Beta estimate method has been demonstrated better than step-wise selection (REF:
Greenland, Am J Epidemiol 2008; 167:523-529).
In fact, I think all variables could be included in the multivariable regression, assuming there is no
correlation between rural/urban and education level.  The study is powered to include 24+ degrees of
freedom (based on 247 patients with constipation), and only 11 degrees of freedom are currently used.
3. Figure 1 is not really observed:expected ratio graph. See the reference for O:E graphs in mortality:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5391699/  
I'm not really sure how you could conduct an observed:expected graph in your case. Your graph is more
the median observed events by age.
4.  Figures  2  demonstrates  the  large  number  of  comparisons  made,  reporting  P-values  for  each
comparison  (which  is  also  discussed  in  the  Results,  Lines  186-195).  Some  will  be  significant
(P&lt;0.05)  simply  by  chance.  Correction  for  multiple  testing  should  be  performed  (Tukey  or
Bonferroni).  
5. Figure 3 does not report standard deviations of the proportions seen, or the delta. The authors should
consider reporting this.
Non-statistical comments:
6. The authors should use the STROBE reporting guidelines to better report their study methods and
results. The methods used in data collection were not always well reported.
7. Where did the original 3031 respondents come from, and why did only 54.2% complete the survey?
Were these representative of the full group?
8. The authors have excluded a large proportion of the population who truly had constipation (anyone
with a medical history involving bowel functioning (proportion not reported), with a history of bowel
surgery (19.9%), somatic diseases influencing the bowel (proportion not reported), congenital disorders
(proportion not reported), medications with constipation as a side effect (9.3%), and other medications
that influence the bowel system (proportion not reported). This would eliminate a large number of
people  with  constipation,  and  29.2%  of  the  respondents,  and  therefore  their  cohort  may  not  be
representative of the typical population.
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.
No
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
No
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:
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 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  has  agreed  to
publication of their comments online under a Creative Commons Attribution License attributed 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.
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: The influence of demographic characteristics on constipation symptoms: A detailed overview
Version: 1 Date: 12 Sep 2019
Reviewer: Research Square Statistical Reviewer
Reviewer's report:
STATISTICAL REVIEWER ASSESSMENT: 
Is the study design appropriate for the research question (considering whether the analyzed population
accurately reflects the design and whether you see any problems with control/comparison groups, e.g.,
likely confounders)?
No - there are major issues
Are methodologies adequate and well implemented (considering whether assumptions are addressed
and whether analyses are robust)?
No - there are minor issues
Are the analyses adequately communicated (considering whether reporting details are adequate and
whether figures and tables are well labeled and described)?
No - there are major issues
Does the interpretation accurately reflect the analyses without overstatement (considering whether
limitations/bias are acknowledged and whether accurate descriptors, e.g., 'significant', are used?
No - there are minor issues
Could an appropriately REVISED version of this work represent a statistically sound contribution? 
Maybe - with major revisions
STATISTICAL REVIEWER COMMENTS:
This  was  an  interesting  study which  assessed  patients  self-reported  constipation  rates,  and  what
symptoms they had. The authors aimed to determine specific patterns of constipation symptoms in
different demographic groups, and to better define symptoms that best indicate functional constipation.
The statistical analysis was generally descriptive statistics, with proportions compared using chi-square
univariate analyses. Some changes are required to the multivariate regression analyses.
REQUESTED REVISIONS: 
Major comments:
1. Logistic regression - the authors tested for 'all assumptions'. However it was not clear whether
interaction terms were tested, or whether correlation/collinearity between covariates was assessed. It is
hard to believe there was no interaction between dietary factors and BMI, or at least these variables
should be correlated? If so, both should not be included in the same multivariable regression, or the
interaction term should be accounted for.
2. The authors used backward step-wise regression (using P-values, with P&lt;0.10) to determine which
confounders were included in multivariable models. This has been shown to be very inefficient and
may result in loss of important data (REF - Derksen &amp; Keselman, British Journal of Mathematical
and Statistical Psychology 1992; 45:265-282.)  Additionally, it relies on only statistical methods of
determining the best model, and not assessment of confounding based on evidence-based clinical
knowledge.  As such, the model developed is prone to the limits of the dataset and may not be
applicable to other studies.  A number of articles have suggested that the best models are constructed a
priori based on extensive review of the literature and expert opinion, and the model should then be
adjusted based on the c-statistic (REFS: Harrell et al., Stat Med 1996; 15:361-387, and Laupacis et al.,
JAMA 1997; 277:488-494).  Alternatively,  selecting including confounding variables  by the 10%
change in the Beta estimate method has been demonstrated better than step-wise selection (REF:
Greenland, Am J Epidemiol 2008; 167:523-529).
In fact, I think all variables could be included in the multivariable regression, assuming there is no
correlation between rural/urban and education level.  The study is powered to include 24+ degrees of
freedom (based on 247 patients with constipation), and only 11 degrees of freedom are currently used.
3. Figure 1 is not really observed:expected ratio graph. See the reference for O:E graphs in mortality:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5391699/  
I'm not really sure how you could conduct an observed:expected graph in your case. Your graph is more
the median observed events by age.
4.  Figures  2  demonstrates  the  large  number  of  comparisons  made,  reporting  P-values  for  each
comparison  (which  is  also  discussed  in  the  Results,  Lines  186-195).  Some  will  be  significant
(P&lt;0.05)  simply  by  chance.  Correction  for  multiple  testing  should  be  performed  (Tukey  or
Bonferroni).  
5. Figure 3 does not report standard deviations of the proportions seen, or the delta. The authors should
consider reporting this.
Non-statistical comments:
6. The authors should use the STROBE reporting guidelines to better report their study methods and
results. The methods used in data collection were not always well reported.
7. Where did the original 3031 respondents come from, and why did only 54.2% complete the survey?
Were these representative of the full group?
8. The authors have excluded a large proportion of the population who truly had constipation (anyone
with a medical history involving bowel functioning (proportion not reported), with a history of bowel
surgery (19.9%), somatic diseases influencing the bowel (proportion not reported), congenital disorders
(proportion not reported), medications with constipation as a side effect (9.3%), and other medications
that influence the bowel system (proportion not reported). This would eliminate a large number of
people  with  constipation,  and  29.2%  of  the  respondents,  and  therefore  their  cohort  may  not  be
representative of the typical population.
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.
No
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
No
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:
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 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  has  agreed  to
publication of their comments online under a Creative Commons Attribution License attributed 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.
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