Review for 10.1186/s12876-024-03575-3 (2025)

Title: Association of Anxiety Status and Anxiety Duration with Constipation in Adult
Americans: A Cross-sectional Study Using Data from the NHANES 2007-2010
Version: 1 Date: 20 Nov 2024
Reviewer:  David McNaughton
Reviewer's report:
Thank for the opportunity to review the manuscript titled “Association between Anxiety
Duration and Constipation in adult Americans: a cross-sectional study using data from the
NHANES 2007–2010”. The authors identified a greater relationship between anxiety duration
in constipated individuals compared to those without classified constipation.
I have some comments to hopefully improve the manuscript. Overall the manuscript provides
some important contributions to the knowledge base, however novelty of the work could be
articulated more clearly and in many instances expression throughout the manuscript reduces
interpretation and clarity of key results.
Abstract
The opening sentence leads causation. Considering the cross-sectional study design, this causal
language should be softened.
Multivariate should be multivariable, considering there is a single dependant variable.
Interpretation of Odd Ratio as the percentage increase is not that precise, I would consider
softening expression to not infer such precision of results.
Further results are not integrated. Particularly stratified analysis of protein consumption is not
set up appropriately.
Introduction
Opening 2 sentences require references, otherwise integrate together.
Broadly the introduction would benefit from a distinction of terminology relevant for the current
study. For example, clearly defining anxiety symptoms vrs. Anxiety disorders. Constipation
symptoms vrs. Constipation as part of a disorder of the brain -gut axis.
The paragraph describing potential mechanisms within the brain-gut axis is appropriate and
important, however, could be refined further to improve clarity. To begin with, I would suggest
a paragraph for each direction with support literature, instead of combing the two. I do believe
this paragraph at present is somewhat a simplistic explanation of the complex brain-gut axis
interaction. I would suggest the author include some more specificity to hypothesized patho-
mechanisms at play.
Rationale for the independent variable anxiety duration needs to the developed further… Why
is the duration of these symptoms important compared having an anxiety disorder, or shorter
time periods.
At present the aims and statistical approach are not consistent. There are several stratified
analysis which do not have any rationale.
Methods
There is some interesting expression at times. Consider refining, such as line 79-80 “….NCHS
is in charge of conducting them” – could be revised to “….NCHS provided oversight to the
design, conduction, management and storage of data related to the NHANES”
Please make sure the manuscript is written in past tense. Several examples throughout have been
noted.
Exclusion of colon cancer and pregnant individuals is appropriate, however is there
information regarding other potential explanations for constipation? Inflammatory conditions,
diverticulosis..
Was there a rationale for the anxiety categories? Or was this the only variable available from
NHANES. It is important the authors are transparent and clear with these methodological
decisions. Further, is there pre existing research to justify this approach.
Line 113 – please refine your academic language  “Covariates included in the statistical models
included…”
Further expression issues in the statistical analysis. Consider revising words such as connection
with relationship or association. Connection does not accurately describe the process being
tested.
Replace “multiple regression analysis” , with “separate multivariable regression analyses”
The statistical analysis section, and broadly your approach, could be structured more and
reflective of your aims. The linear correlations analysis via smooth fitting curves, is not set up
in the introduction, nor explicitly described as an aim. At present it reads such as an exploratory
post hoc analysis. I would suggest, either clearly outline this as a post hoc analysis or provide an
aim and clear rationale / hypothesis in the introduction to support this approach. Why did you
suspect changes in the correlations between anxiety and constipation at different ages? Further
clarity around the stratified analysis would also be good (rationale, approach, aim it related to?)
Results
Some areas could be refined further, for example – it is not necessary to report both male and
female proportions in text. It is assumed the remaining proportion is for the opposite sex, these
subtle expression and sentence construction issues, detract from the flow and communication
of key results.
I am unsure what correlation with hypertension and constipation is being tested. does this refer
to the between group difference? If so, I would communicate this more accurately.
Further clarification required to the proportions, it may be helpful to present both the numerator
and denominator with the key in text proportions. That way it is clear what is being references
reflective of the data. Especially sub-groups within the total data are being presented.
Line 169, Some more expression issues – the table doesn’t reveal, results from Table 1
“presented or identified”.
Line 173 replace suffering with “with” – you have not measured the subjective impact of
constipation, only the frequency and consistency of stools.
It would be appropriate to present 95% CI to give an estimate of the degree of precision of the
findings, especially that presented in text. I believe we are moving away from soley reporting
p-values.
Line 181 – found to have a “statistically” significant association. There are a few instances where
this occurs.
Also, there are multiple analyses presented in the univariate approach’s, thus analysis should
be plural.
While OR of 2.0 generally relates to a doubling of the effect, An OR of 2.38 does not equate
to exactly a 138% increase in risk. I would avoid terminology that infers such precision of the
results and soften language around this.
The stratified analysis presented in text is unclear to how things were stratified. More clarity and
specificity are required when communicating these findings. It is also not clear to me from the
statistical analysis the approach taken here… considering this is reported as key findings, some
more time in the statistical analysis section should be made to outline the approach.
Also Figure 3 is presented in text prior to figure 2? – it is these little errors which are making
the manuscript quite difficult to read, follow, and interpret
Similar interpretation of odds ratios throughout the results. The precision of the proportional
increase in risk , ie. 10%, articulated is not accurate. Please soften the precise language
and consider revision to something like “a positive, small and non-statistically significant
relationship was identified.”
Table 3 - I am surprised by these results.. Model 1 is not statistically significant, however model
2, which includes the covariates from model 1, in addition to several others, is statistically
significant and larger. These findings contradict one another.. can the authors please comment
on this.
More clarity in the paragraph reporting table 4 is encouraged.
It is also a little confusing anxiety duration cut offs are used in the regression models, however
the smooth fitting curve it is now used a continuous variable? Please clarify the approaches
taken here.
Discussion
Line 250 – “representative sample of the US population”.
Please elaborate further regarding the curvilinear relationship with constipation and anxiety in
older populations. This is communicated as a key finding, however limited explanation of this
finding is provided in the discussion.
Some analysis of the potential and likely bidirectional relationship at play is required.
It is true, increasing numbers of chronic illnesses are related to worse psychological function,
however the discussion regarding the “top-down” influence of anxiety on constipation, is in
my opinion, quite simplistic. I would encourage the authors to integrate literature that helps
explain the relationship of coping mechanisms, mood alterations, and behavioural changes with
the perception and experience of constipation in more detail. This discussion would balance the
quite explicit biomedical explanations of the relationship the follow.
Please elaborate further on the conflicting multivariable regression analyses results in the
discussion.
It is also not clear regarding the focus on protein intake results in the discussion. Figure 4, seems
several other factors are also statistically significant, however not discussed.