Influence of Chronic Fatigue Syndrome Codiagnosis on the Relationship between Perceived and Objective Psychoneuro-Immunoendocrine Disorders in Women with Fibromyalgia

Round 1

Reviewer 1 Report

The paper is well written and thorough. The introduction is adequate and helps the reader to move smoothly through the topic at hand. The method states that normality tests have been performed. Although reference is made to parametric and non-parametric variables, it is not clearly specified which they are. Although the sample is small, the inclusion of only women in the study could justify this. References are relevant to the topic and no inappropriate self-references were observed. The conclusion is relevant to all of the above.

My thought is whether it should be stated in the limitations that only one gender is considered. It should be mentioned whether the fact that most of them are overweight affects the considered indicators. Also, it is not clarified whether their hormonal profile (menopausal women) has any effect on both the indicators and the questionnaires they fill out themselves.

Author Response

Reviewer 1 Comments

Firstly, thank you very much for your effort and positive criticism in order to improve the manuscript. We have take into account all your considerations.

The paper is well written and thorough. The introduction is adequate and helps the reader to move smoothly through the topic at hand. The method states that normality tests have been performed. Although reference is made to parametric and non-parametric variables, it is not clearly specified which they are. Although the sample is small, the inclusion of only women in the study could justify this. References are relevant to the topic and no inappropriate self-references were observed. The conclusion is relevant to all of the above.

First of all, we would like to thank you for your very positive comments and, particularly, for your suggestion. Non-parametric or parametric statistical studies are now included in the legends of the figures (in red).

My thought is whether it should be stated in the limitations that only one gender is considered. It should be mentioned whether the fact that most of them are overweight affects the considered indicators. Also, it is not clarified whether their hormonal profile (menopausal women) has any effect on both the indicators and the questionnaires they fill out themselves.

Thank you for your suggestions. In our honest opinion, we cannot consider as a limitation the fact that only women were used in our study, taking into account that the vast majority of these patients are women and we do not have male volunteers (that, in our opinion, must be considered in a separate group). Overweight (also age, gender, menopausal characteristics, etc) could affect some neuroendocrine biomarkers, this is the reason for our correct age-matched control reference group (with the same age and anthropometric characteristics).

Reviewer 2 Report

Thankyou for submitting your article to the Journal.

Ln 45 – 48. You state that there is a clear relationship between FM and the HPA axis and quote your previous work to support this. Are there other groups also supporting your work (ie similar findings?). You also don’t discuss whether these findings are a cause of FM or a result of FM

CFS (some people call Myalgic encephalomyelitis ME) and FM have much overlap do you think they are a spectrum of the same underlying condition?

FM and CFS codiagnosis might be disputed depending on the criteria used to make the diagnoses. The symptom severity score of ACR has Fatigue as a significant component of its scoring system.

Materials and Methods

Ln 92 you present results of the anthropometric details here, this would be better under Results

Ln 103 How did you measure the Visceral fat index/Body composition?

Ln 113 you discuss using an accelerometer to make objective measures of physical activity.

This might be affected or biased depending on exactly what instructions were given to the participants. For example they might have tried hard to exercise. Were any participants in active treatment for there conditions which would include exercise. The exclusion (e) Ln 89

Is hard to understand how it might affect the results?

Ln 190 spell out DHEA IL-8, IL-10

Results ln 209

Consider delete “Only as expected …” this is comment and should not relate to the results you found at this stage.

Generally your results are interesting and I note you have the statistical significance levels identified.

In Discussion maybe you can consider if these results are likely to be clinically significant.

I note you discuss response bias on Ln 377 see my comments above about accelerometry.

 Thankyou for submitting your article to the Journal.

Ln 45 – 48. You state that there is a clear relationship between FM and the HPA axis and quote your previous work to support this. Are there other groups also supporting your work (ie similar findings?). You also don’t discuss whether these findings are a cause of FM or a result of FM

CFS (some people call Myalgic encephalomyelitis ME) and FM have much overlap do you think they are a spectrum of the same underlying condition?

FM and CFS codiagnosis might be disputed depending on the criteria used to make the diagnoses. The symptom severity score of ACR has Fatigue as a significant component of its scoring system. 

Materials and Methods

Ln 92 you present results of the anthropometric details here, this would be better under Results

Ln 103 How did you measure the Visceral fat index/Body composition?

Ln 113 you discuss using an accelerometer to make objective measures of physical activity.

This might be affected or biased depending on exactly what instructions were given to the participants. For example they might have tried hard to exercise. Were any participants in active treatment for there conditions which would include exercise. The exclusion (e) Ln 89 

Is hard to understand how it might affect the results? 

Ln 190 spell out DHEA IL-8, IL-10

Results ln 209

Consider delete “Only as expected …” this is comment and should not relate to the results you found at this stage.

Generally your results are interesting and I note you have the statistical significance levels identified.

In Discussion maybe you can consider if these results are likely to be clinically significant.

I note you discuss response bias on Ln 377 see my comments above about accelerometry.

nil

Author Response

Reviewer 2 Comments

Firstly, thank you very much for your effort and positive criticism in order to improve the manuscript. We have take into account all your considerations.

Thankyou for submitting your article to the Journal.

Ln 45 – 48. You state that there is a clear relationship between FM and the HPA axis and quote your previous work to support this. Are there other groups also supporting your work (ie similar findings?). You also don’t discuss whether these findings are a cause of FM or a result of FM

 Thank you for your suggestions. But actually it was already included in the discussion section (Ln 437-443). In any case, if you feel that relevant references are lacking, specify us, please.

CFS (some people call Myalgic encephalomyelitis ME) and FM have much overlap do you think they are a spectrum of the same underlying condition?

 FM and CFS codiagnosis might be disputed depending on the criteria used to make the diagnoses. The symptom severity score of ACR has Fatigue as a significant component of its scoring system.

 Good question. According to our results, we cannot to ensure it, although perceived anxiety and stress (together with low pain umbral and fatigue could be stated).

Materials and Methods

Ln 92 you present results of the anthropometric details here, this would be better under Results

 Thank you, you are right. We also feel that it is better. It has been modified in the text (in red).

 Ln 103 How did you measure the Visceral fat index/Body composition?

 Sorry for the mistake. It is now included in method section ( 2.2. Body composition measurements; Bioimpedance Analisis) (in red).

Ln 113 you discuss using an accelerometer to make objective measures of physical activity.

This might be affected or biased depending on exactly what instructions were given to the participants. For example they might have tried hard to exercise. Were any participants in active treatment for there conditions which would include exercise. The exclusion (e) Ln 89 Is hard to understand how it might affect the results?

 I note you discuss response bias on Ln 377 see my comments above about accelerometry.

 In fact, this is the reason why exclusion criteria (e) is included. That is why fibromyalgia associations keep a close eye on the physical activity programs of the patients. In addition, our instructions were very clear regarding no physical exercise; they were only to perform daily activities during the week of measurement.

 Ln 190 spell out DHEA IL-8, IL-10

 They have been spelled out in Method section (in red). Thank you.

 Results ln 209

Consider delete “Only as expected …” this is comment and should not relate to the results you found at this stage.

 You are right, Thank you. It has been deleted.

  Generally your results are interesting and I note you have the statistical significance levels identified.

 Thank you for your comment.

In Discussion maybe you can consider if these results are likely to be clinically significant.

  Thank you for your suggestion. We have included a paragraph on this at the end of the discussion (in red).