Title: Absent or impaired rectoanal inhibitory reflex as a diagnostic factor for high-grade (grade
III–V) rectal prolapse: a retrospective study
Version: 1 Date: 13 Jan 2021
Reviewer's report:
In this manuscript, Dr. Park and colleagues performed a retrospective analysis of patients
presenting to a tertiary care center with anorectal complaints (including fecal incontinence,
constipation, and anorectal discomfort) who underwent both anorectal manometry and
defecography. They found that an abnormal rectoanal inhibitory response (RAIR) was
associated with high-grade rectal prolapse (Grades III-V) according to the Oxford classification
—with an association that persisted after multivariable control. There was a significant trend of
a higher proportion of abnormal RAIR associated with increasing degree of prolapse.
MAJOR COMMENTS
1.   Since this is a retrospective study, the association between abnormal RAIR and prolapse was
presumably an exploratory endpoint—i.e. the authors did not set out to prove this in advance
but were looking at predictors of prolapse in a cohort with multiple measured parameters.
This is absolutely fine, but the Introduction adopts a tone assuming that this was the a. priori
assumption of the analysis. I think the Introduction would be improved by addressing the
gaps in our ability to diagnose prolapse without more unpleasant testing (defecography) with
acknowledgement that the authors were likely looking for all associations and that absent RAIR
was most compelling.
2.  The Abstract would benefit from increased detail in the Methods, for example the fact that
symptom report was included as part of each patient’s assessment.
3.  How was clinical data collected from patients? Were validated patient-reported outcomes
used or were the responses to clinical questions yes/no. It would be helpful to know which
questions were asked and how were symptoms graded (continuous scale, categorical, yes/no).
4.  There are 30 “outcomes” as part of this analysis (30 patients with high-grade prolapse). Thus,
the general rule for multivariable adjustment is no more than 3 variables should be adjusted for
(rule of 10s). The included model is likely over-adjusted.
5.  It would be helpful to have more detail about the ROC analysis used to determine cutoff
values for inclusion in the multivariable analysis. Why not include these variables as continuous
covariates?
6.  It would be nice to include a sensitivity and specificity for abnormal RAIR as a predictor of
high-grade prolapse (since these are not related to disease prevalence).  Looks like sensitivity
is about 63% and specificity 74%.
Title: Absent or impaired rectoanal inhibitory reflex as a diagnostic factor for high-grade (grade
III–V) rectal prolapse: a retrospective study
Version: 1 Date: 13 Jan 2021
Reviewer's report:
In this manuscript, Dr. Park and colleagues performed a retrospective analysis of patients
presenting to a tertiary care center with anorectal complaints (including fecal incontinence,
constipation, and anorectal discomfort) who underwent both anorectal manometry and
defecography. They found that an abnormal rectoanal inhibitory response (RAIR) was
associated with high-grade rectal prolapse (Grades III-V) according to the Oxford classification
—with an association that persisted after multivariable control. There was a significant trend of
a higher proportion of abnormal RAIR associated with increasing degree of prolapse.
MAJOR COMMENTS
1.   Since this is a retrospective study, the association between abnormal RAIR and prolapse was
presumably an exploratory endpoint—i.e. the authors did not set out to prove this in advance
but were looking at predictors of prolapse in a cohort with multiple measured parameters.
This is absolutely fine, but the Introduction adopts a tone assuming that this was the a. priori
assumption of the analysis. I think the Introduction would be improved by addressing the
gaps in our ability to diagnose prolapse without more unpleasant testing (defecography) with
acknowledgement that the authors were likely looking for all associations and that absent RAIR
was most compelling.
2.  The Abstract would benefit from increased detail in the Methods, for example the fact that
symptom report was included as part of each patient’s assessment.
3.  How was clinical data collected from patients? Were validated patient-reported outcomes
used or were the responses to clinical questions yes/no. It would be helpful to know which
questions were asked and how were symptoms graded (continuous scale, categorical, yes/no).
4.  There are 30 “outcomes” as part of this analysis (30 patients with high-grade prolapse). Thus,
the general rule for multivariable adjustment is no more than 3 variables should be adjusted for
(rule of 10s). The included model is likely over-adjusted.
5.  It would be helpful to have more detail about the ROC analysis used to determine cutoff
values for inclusion in the multivariable analysis. Why not include these variables as continuous
covariates?
6.  It would be nice to include a sensitivity and specificity for abnormal RAIR as a predictor of
high-grade prolapse (since these are not related to disease prevalence).  Looks like sensitivity
is about 63% and specificity 74%.
Please review this paper.
user
Title: Absent or impaired rectoanal inhibitory reflex as a diagnostic factor for high-grade (grade
III–V) rectal prolapse: a retrospective study
Version: 1 Date: 13 Jan 2021
Reviewer's report:
In this manuscript, Dr. Park and colleagues performed a retrospective analysis of patients
presenting to a tertiary care center with anorectal complaints (including fecal incontinence,
constipation, and anorectal discomfort) who underwent both anorectal manometry and
defecography. They found that an abnormal rectoanal inhibitory response (RAIR) was
associated with high-grade rectal prolapse (Grades III-V) according to the Oxford classification
—with an association that persisted after multivariable control. There was a significant trend of
a higher proportion of abnormal RAIR associated with increasing degree of prolapse.
MAJOR COMMENTS
1.   Since this is a retrospective study, the association between abnormal RAIR and prolapse was
presumably an exploratory endpoint—i.e. the authors did not set out to prove this in advance
but were looking at predictors of prolapse in a cohort with multiple measured parameters.
This is absolutely fine, but the Introduction adopts a tone assuming that this was the a. priori
assumption of the analysis. I think the Introduction would be improved by addressing the
gaps in our ability to diagnose prolapse without more unpleasant testing (defecography) with
acknowledgement that the authors were likely looking for all associations and that absent RAIR
was most compelling.
2.  The Abstract would benefit from increased detail in the Methods, for example the fact that
symptom report was included as part of each patient’s assessment.
3.  How was clinical data collected from patients? Were validated patient-reported outcomes
used or were the responses to clinical questions yes/no. It would be helpful to know which
questions were asked and how were symptoms graded (continuous scale, categorical, yes/no).
4.  There are 30 “outcomes” as part of this analysis (30 patients with high-grade prolapse). Thus,
the general rule for multivariable adjustment is no more than 3 variables should be adjusted for
(rule of 10s). The included model is likely over-adjusted.
5.  It would be helpful to have more detail about the ROC analysis used to determine cutoff
values for inclusion in the multivariable analysis. Why not include these variables as continuous
covariates?
6.  It would be nice to include a sensitivity and specificity for abnormal RAIR as a predictor of
high-grade prolapse (since these are not related to disease prevalence).  Looks like sensitivity
is about 63% and specificity 74%.
assistant