Title: Anorectal Manometry for the Diagnosis of Pelvic Floor Disorders in Patients with
Hypermobility Spectrum Disorders and Hypermobile Ehlers-Danlos Syndrome
Version: 3 Date: 11 Aug 2022
Reviewer's report:
Thank you for addressing my comments and incorporating the  changes into your manuscript.
It would have been helpful to have the changes in the manuscript highlighted to make it easier
to spot these.
There remain a few unresolved issues which I will list here:
1. Abstract conclusion remains inaccurate: Anorectal pressure profile IS compromised as you
had significantly more patients with a negative rectoanal pressure gradient. Also it was only
in hEDS that you found that maximal tolerated volume (ie reduced rectal sensation) predicted
an abnormal BET so something different is happening in the hEDS patients compared to the
controls and I think this is a very important finding and one that needs to be discussed and
included in the conclusion, particularly in light of the APT paper by Choudhary et al. I do not
think you can conclude that it is all psychosomatic or psychological.
2. You mention that you used the 2017 classification to diagnose hEDS. However the study was
retrospective and the classification was not available in 2014 , when data was collected. Can
you explain how you used the 2017 classification in patients recruited from 2014-2017?
3. In your results when referring to table 2 you ignore the fact that the rectoanal pressure gradient
was significantly more negative in the hEDS patients.
4. In Table 4 why do you not show all the variables you have put in your regression model? I
take your point (in response to my comments) that you wanted to use continuous rather than
categorical data in the model but can you then explain why you only used one sensory level
(volume of first sensation) rather than 2, as you state quite explicitly that you need to use both
sensory levels to make a diagnosis of rectal hyposensitivity. I suspect you may have done the
regression model with more than one sensory level as in the discussion you state: In HSD/
hEDS patients, higher resting sphincter pressures and rectal sensory level for maximum tolerated
volume were associated with abnormal BET, while a more negative rectoanal gradient was
associated with abnormal BET in non HSD patients. Please can you demonstrate these results
in the table as they are currently not there
5. The discussion remains confusing, particularly with its flow. It may be helpful to start with
a summary of all the positive findings. I would also suggest that the discussion focuses on the
subject of the title as currently it meanders a bit.
Title: Anorectal Manometry for the Diagnosis of Pelvic Floor Disorders in Patients with
Hypermobility Spectrum Disorders and Hypermobile Ehlers-Danlos Syndrome
Version: 3 Date: 11 Aug 2022
Reviewer's report:
Thank you for addressing my comments and incorporating the  changes into your manuscript.
It would have been helpful to have the changes in the manuscript highlighted to make it easier
to spot these.
There remain a few unresolved issues which I will list here:
1. Abstract conclusion remains inaccurate: Anorectal pressure profile IS compromised as you
had significantly more patients with a negative rectoanal pressure gradient. Also it was only
in hEDS that you found that maximal tolerated volume (ie reduced rectal sensation) predicted
an abnormal BET so something different is happening in the hEDS patients compared to the
controls and I think this is a very important finding and one that needs to be discussed and
included in the conclusion, particularly in light of the APT paper by Choudhary et al. I do not
think you can conclude that it is all psychosomatic or psychological.
2. You mention that you used the 2017 classification to diagnose hEDS. However the study was
retrospective and the classification was not available in 2014 , when data was collected. Can
you explain how you used the 2017 classification in patients recruited from 2014-2017?
3. In your results when referring to table 2 you ignore the fact that the rectoanal pressure gradient
was significantly more negative in the hEDS patients.
4. In Table 4 why do you not show all the variables you have put in your regression model? I
take your point (in response to my comments) that you wanted to use continuous rather than
categorical data in the model but can you then explain why you only used one sensory level
(volume of first sensation) rather than 2, as you state quite explicitly that you need to use both
sensory levels to make a diagnosis of rectal hyposensitivity. I suspect you may have done the
regression model with more than one sensory level as in the discussion you state: In HSD/
hEDS patients, higher resting sphincter pressures and rectal sensory level for maximum tolerated
volume were associated with abnormal BET, while a more negative rectoanal gradient was
associated with abnormal BET in non HSD patients. Please can you demonstrate these results
in the table as they are currently not there
5. The discussion remains confusing, particularly with its flow. It may be helpful to start with
a summary of all the positive findings. I would also suggest that the discussion focuses on the
subject of the title as currently it meanders a bit.
Please review this paper.
user
Title: Anorectal Manometry for the Diagnosis of Pelvic Floor Disorders in Patients with
Hypermobility Spectrum Disorders and Hypermobile Ehlers-Danlos Syndrome
Version: 3 Date: 11 Aug 2022
Reviewer's report:
Thank you for addressing my comments and incorporating the  changes into your manuscript.
It would have been helpful to have the changes in the manuscript highlighted to make it easier
to spot these.
There remain a few unresolved issues which I will list here:
1. Abstract conclusion remains inaccurate: Anorectal pressure profile IS compromised as you
had significantly more patients with a negative rectoanal pressure gradient. Also it was only
in hEDS that you found that maximal tolerated volume (ie reduced rectal sensation) predicted
an abnormal BET so something different is happening in the hEDS patients compared to the
controls and I think this is a very important finding and one that needs to be discussed and
included in the conclusion, particularly in light of the APT paper by Choudhary et al. I do not
think you can conclude that it is all psychosomatic or psychological.
2. You mention that you used the 2017 classification to diagnose hEDS. However the study was
retrospective and the classification was not available in 2014 , when data was collected. Can
you explain how you used the 2017 classification in patients recruited from 2014-2017?
3. In your results when referring to table 2 you ignore the fact that the rectoanal pressure gradient
was significantly more negative in the hEDS patients.
4. In Table 4 why do you not show all the variables you have put in your regression model? I
take your point (in response to my comments) that you wanted to use continuous rather than
categorical data in the model but can you then explain why you only used one sensory level
(volume of first sensation) rather than 2, as you state quite explicitly that you need to use both
sensory levels to make a diagnosis of rectal hyposensitivity. I suspect you may have done the
regression model with more than one sensory level as in the discussion you state: In HSD/
hEDS patients, higher resting sphincter pressures and rectal sensory level for maximum tolerated
volume were associated with abnormal BET, while a more negative rectoanal gradient was
associated with abnormal BET in non HSD patients. Please can you demonstrate these results
in the table as they are currently not there
5. The discussion remains confusing, particularly with its flow. It may be helpful to start with
a summary of all the positive findings. I would also suggest that the discussion focuses on the
subject of the title as currently it meanders a bit.
assistant