Title: THE ROLE OF LIFESTYLE FACTORS IN THE ASSOCIATION BETWEEN
EDUCATION AND SELF-REPORTED FIBROMYALGIA: A MEDIATION ANALYSIS
Version: 1 Date: 04 Jan 2024
Reviewer:  Inger Haukenes
Reviewer's report:
Overall: This study examines the relationship between educational level and fibromyalgia (FM),
and the potential contribution of lifestyle mediators. The study is well performed and presented,
and the authors have performed several additional analyses (sensitivity analyses) to support
the validity of their findings. There are, however, some points that need clarification and some
important findings may need a wider perspective in the discussion.
These are my comments.
Methods
- NOWAC: please provide the aims of NOWAC, the inclusion criteria for participation and the
response rate, as a minimum. Reference to information elsewhere is okay but a minimum of
information for the reader should be provided in the manuscript.
- Are covariates collected from the baseline questionnaire?
- In the theoretical model, covariates are positioned intermediate of exposure and outcome
(as time-dependent mediators), does this mean that information of covariates are not baseline
information?
- Could you please explain how you define a mediator, and would you think that a mediator
should be situated between exposure and outcome in time?
Statistical analyses.
- Figure 2 When explaining the figure, you repeat what is already presented in the introduction.
I suggest that you reduce the level of specificity and provide an overall statement that the chosen
lifestyle mediators are associated both with FM (+ references) and with education (+ references).
- Page 9, second paragraph towards the end you use the word ‘uncausally’ correlated, could you
please explain the meaning of this statement in relation to the analyses?
- The Cox Proportional Hazard Model relies on the assumption of proportional hazards (PH)
across covariates. Did you test the proportional hazards assumption, what were the results and
how did you deal with potential non-proportionality?
- A review of studies using cox regression analyses ‘Testing the proportional hazards assumption
(PH) in cox regression and dealing with possible non-proportionality in total joint arthroplasty
research: methodological perspectives and review’ in BMC Musculoskeletal Disorders found
that a minority of studies mentioned PH assumption, tested PH assumption, tested method of
the PH assumption named, mentioned the result of the testing, and corrected the Cox regression
model, if required.
Results:
- First sentence: I suggest you check if this is a repetition of what is already presented in the
methods.
- First paragraph: Overweight, obesity, very low and very high levels of physical activity
were observed more frequently among those with # 9 years of education, compared with their
counterparts. Does this mean that lower educated placed themselves at the extreme ends of the
scale, whereas higher educated were more homogeneous in their reporting? I am not sure your
findings support this interpretation.
- Table 1. Considering the aims of the study, I would suggest that you focus on reporting the
educational gradient, potential inverse gradients, and other interesting findings. For instance,
alcohol consumption displays an inverse social gradient, depression is only 1.5 percent points
higher among the lower educated versus higher, and 17% of lower educated are #60 compared
to the higher educated (6.4% and 4.1%). With respect to distribution of level of physical activity
across educational level there are only minor differences – I would say that the trend is rather
similar. BMI is typically socially distributed as well as smoking. There may be a smoking-
generation issue connected to the age distribution among lower educated. This information may
be relevant when interpreting the results of the Cox regression.
- I miss a figure (4) presenting the highest educated.
Discussion:
General: I would suggest you try to avoid presenting findings in detail that are already presented
in the result chapter.
- Sentence two: (…..) significant inverse association between education and FM (…). I suggest
you reformulate it so that it is easier to grasp the main finding of an educational gradient in FM.
- The study of Choi et al. is interesting, and I suggest you list the factors adjusted for in their
study, and comment on their explanatory value.
- Maybe health literacy should be added to the explanation for the educational gradient. Health
literacy would suit well in your discussion.
- Page 15, third paragraph concerning the inverse educational gradient in alcohol consumption.
This needs to be discussed carefully. First, it is problematic to interpret your finding in the
direction that FM among lower educated could be ‘reduced by 8.2% if the distribution of alcohol
consumption in those with # 9 years of education is brought to the level observed in those
with #13 years of education’. In principle this means that lower educated should increase their
drinking.  It is difficult to find support for you explanation in reference 62, as your population
is mainly women in all ages who are less likely to ‘drink heavily’ compared with men. This
goes for the hypothesis of inclusion of former drinkers/comorbidity among lower educated –
you need to discuss to what extent this argument is valid for women. Thus, I find it highly
difficult to explain this finding without going into the sum of burdens among lower educated
women, and the possibility of a higher vulnerability for negative health outcomes even with
lower level of exposure (ref Diderichsen: The Social Basis of Disparities in health,  i.e  a given
risk factor may be distributed evenly across social groups, however, its impact on health may be
unevenly distributed’). I suggest you reformulate this paragraph and take a gender perspective
and a vulnerability perspective into account.
Strength and limitations
- Page 18, last paragraph. Is there any reason to believe that recall bias in self-reporting of
lifestyle factors differs across educational levels? If not, recall bias is less likely to affect the
findings and the internal validity.
Conclusion
- As previously explained, I miss the vulnerability approach in your conclusion.