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ARTICLE DETAILS
TITLE (PROVISIONAL)
AUTHORS
Fatigue and its associated factors in liver transplant recipients in
Beijing: a cross-sectional study
Lin, Xiaohong; Teng, Sha; Wang, Lu; Zhang, Jing; Shang, Ya-Bin;
Liu, Hong-Xia; Zang, Yun-Jin
VERSION 1 - REVIEW
REVIEWER
REVIEW RETURNED
GENERAL COMMENTS
Weng, Li-Chueh
School of Nursing, College of Medicine, Chang Gung University,
Taiwan, ROC
06-Jun-2016
Abstract: page 2/15, line 30-36, please present indicate the direction
of association among variables (e.g. positive or negative).
Introduction: page 3/15, third paragraph, please provides more
explanations on the significance of investigating the influence factors
of fatigue.
Measurement: page 4/15, line 23, please revises the term
“cadavers” to “deceased”.
Measurement: page 4/15, as author’s mention in the introduction
section, three categories of factors may influence patient’s symptom
experience as well as fatigue. Thus, the measurement part, in
particular the factors of fatigue should re-organize to reflect these
arguments. In addition, the physical category of factors was less
mention in this study, it may provide as limitation.
Ethical consideration: page 5/15, please provide an approval
number of IRB, if applicable.
Table 3: page 8/15, please indicate is the gender male or female?
Conclusion: page 11/15, please provide more descriptions specific
to clinical implication.
Discussion: page 9/15, “87.0% liver transplant recipients reported
fatigue…” . This number did not present in the result section. Please
provide an explanation how the percentage be calculated. In
addition, there is inconsistent in the abstract (87.02%) and
discussion section (87.0%). Please clarify it.
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REVIEWER
REVIEW RETURNED
GENERAL COMMENTS
Mr. Thamara Perera MBBS, MS, FEBS, MD, FRCS
The Liver Unit
Queen Elizabeth Hospital Birmingham
Edgbaston
Birmingham
United Kingdom
18-Jul-2016
The article "Fatigue and its Associated factors in liver transplant
recipients in Beijing: a cross-sectional study" by Lin et al was
reviewed with interest. Liver transpalntation has established its place
as the best treatment option for those with ESLD and hepatocellular
cancer amongst its main indications and currently have excellent
long term outcomes. However other aspects following this life saving
procedure, namely the physical and psychological well being is
probably less well studied or published in the literature and in this
background this study is commendable.
Comments:
01. Sarcopenia and encepahlopathy are key symptoms of patients
with encephalopathy that are associated with poor nutrition
impacting on post transplant recovery. On the other hand loss of
skeletal muscle mass is associated with fatigue therefore functional
recovery after LT may take much longer than anticipated. This
aspect should be added to the introduction.
02. Also authors should provide the data with regards to teh
nutritional and sarcopenic status of their patient group.
03. It is important that autors separate the early post transpalnt
patient group with late post transpalnt group. It is well known that full
functional recovery takes at least 3-6 months in a starght forward
post transplant recipeint however in complicated cases this may
extend beyond six months. From the given data it appears the
functional status of 3month post LT patient is compared with that of
nealry 10year post LT patient. In my opinion there has to be
subgroup analysis of early vs. late post transplant and given their
study group this should be feasible.
04. What were the indications, MELD scores and post transplant
status of these patients. It is not surprising that complicated patients
have more longer recovery and inclreased fatigue, anxiety and
insomnia (some of it is related to mediction etc) hence their should
be a breakdown of the results by presence or absence of
complications following transplant (ex: Clavien Dindo grade III or
above)
05. Please consider changing the terminology "fatgue now" and
"fatigue in the last week" that have been used throughout the
manuscript. These should be referred to te point of assessment,
perhaps could be termed as "fatigue at the point of assesment" and
"the week prior to assesment" respectively.
Overall the manuscript is well written and provide insight in to less
well addressed issues following LT, provided the above mentioned
two sub-group analyses were performed
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VERSION 1 – AUTHOR RESPONSE
Reviewer: 1
Reviewer Name : Weng, Li-Chueh
Comments:
1. Abstract: page 2/15, line 30-36, please present indicate the direction of association among
variables (e.g. positive or negative).
Response: We are very sorry for our negligence of the direction of association. We have made
correction according to the Reviewer’s comments in Abstract.
2. Introduction: page 3/15, third paragraph, please provides more explanations on the significance of
investigating the influence factors of fatigue.
Response: We have re-written this part according to the Reviewer’s suggestion, Line 7~10 in this
paragraph, “Severe fatigue may reduce LT recipients’ daily activites and hinder their recovery and
return to work. For those recipients who had back to work, chronic fatigue may reduce their work
efficiency and increase security risks. In addition, long-term fatigue may increase negative emotions.”
was added.
3.Measurement: page 4/15, line 23, please revises the term “cadavers” to “deceased”.
Response: We have made correction according to the Reviewer’s comments.
4.Measurement: page 4/15, as author’s mention in the introduction section, three categories of factors
may influence patient’s symptom experience as well as fatigue. Thus, the measurement part, in
particular the factors of fatigue should re-organize to reflect these arguments. In addition, the physical
category of factors was less mention in this study, it may provide as limitation.
Response: It is really true as Reviewer suggested that we should re-organize the factors of fatigue in
our study to reflect three categories of factors in TOUS. Line 8~13 in this paragraph, “According to the
theory of unpleasant symptoms, these above-mentioned variables which may influence LT recipients’
fatigue symptom can be divided into three categories. Physiological factors included recipients’ age,
gender, BMI, duration after LT (calculated by the date of transplant and the date of assesment) and
insomnia. Psychological factors included anxiety and depression, while situational factors included
recipients’ employment status and social support.” was added.
5.Ethical consideration: page 5/15, please provide an approval number of IRB, if applicable.
Response: We are sorry that there is no approval number in our ethical approval IRB. We can provide
the COPY of ethical approval document if necessary.
6.Table 3: page 8/15, please indicate is the gender male or female?
Response: We have made correction according to the Reviewer’s comments.
7.Conclusion: page 11/15, please provide more descriptions specific to clinical implication.
Response: We have re-written this part according to the Reviewer’s suggestion, Line 3~5 in this
paragraph, the statements of “Health care providers should pay more attention on recipients’ fatigue
and other co-exist symptoms. Some intervention, such as rehabilitation program, antidepressant
drugs treatment, and sleep medicine, may be helpful.” were corrected as “The recipients who had
severe insomnia and mood disorders, felt severer fatigue and greater influence caused by fatigue. It
suggests that health care providers should not only pay more attention on recipients’ fatigue but also
on other co-exist symptoms. Some intervention, such as rehabilitation program, antidepressant drugs
treatment, and sleep medicine, may be necessary and helpful.”
8.Discussion: page 9/15, “87.0% liver transplant recipients reported fatigue…” . This number did not
present in the result section. Please provide an explanation how the percentage be calculated. In
Downloaded from http://bmjopen.bmj.com/ on June 14, 2017 - Published by group.bmj.com
addition, there is inconsistent in the abstract (87.02%) and discussion section (87.0%). Please clarify
it.
Response: We are very sorry for our incorrect writing of number in abstract (87.02%), and we have
corrected the number as 87.0%. In the result section, page 7/14, line 1~2, “A total of 248 (87.0%) LT
recipients reported fatigue on the average in the week prior to assesment (their average fatigue score
> 0).” was added.
Special thanks to you for your good comments!
Reviewer: 2
Reviewer Name : Mr. Thamara Perera MBBS, MS, FEBS, MD, FRCS
Comments:
01. Sarcopenia and encepahlopathy are key symptoms of patients with encephalopathy that are
associated with poor nutrition impacting on post transplant recovery. On the other hand loss of
skeletal muscle mass is associated with fatigue therefore functional recovery after LT may take much
longer than anticipated. This aspect should be added to the introduction.
Response: We are very sorry for our negligence of “sarcopenia and encepahlopathy” in our
introduction. Line 14~18, “Sarcopenia, a frequent complication in cirrhosis, while the loss of skeletal
muscle mass may lead to patients’ fatigue, was reported to have adverse effect on patients’ recovery
and post liver transplantation survival [9]. Another complication in cirrhosis, hepatic encephalopathy,
may be another reason for patients’ fatigue, for it is related to anemia and fat-free mass depletion
[10]. ” was added.
02. Also authors should provide the data with regards to the nutritional and sarcopenic status of their
patient group.
Response: It is really true as Reviewer suggested that we should provide the data with regards to the
nutritional and sarcopenic status of our patient group, however, we had only measured recipients’
BMI. We added the following statement in Limitations, “We only measured LT recipients’ BMI, and
other indices of their nutritional and sarcopenic status were not assessed and measured......More
influencing factors, such as recipients’ nutritional status, sarcopenic status, ...... should be considered
and explored in the future research.”
03. It is important that autors separate the early post transpalnt patient group with late post transpalnt
group. It is well known that full functional recovery takes at least 3-6 months in a starght forward post
transplant recipeint however in complicated cases this may extend beyond six months. From the
given data it appears the functional status of 3month post LT patient is compared with that of nealry
10year post LT patient. In my opinion there has to be subgroup analysis of early vs. late post
transplant and given their study group this should be feasible.
Response: As Reviewer suggested that there has to be subgroup analysis of early vs. late post
transplant, we have divided 285 LT recipients into early post transplant recipient group (time after LT
≤ 5 years) and late post transplant recipient group (time after LT > 5 years), and compared the FSI
13-item scores between the two groups. The corresponding analysis result and conclusion were
added in Result part ( Page 8~9/14, paragraph 1 and Table 3) and Conclusion part (Page 10/14 ).
04. What were the indications, MELD scores and post transplant status of these patients. It is not
surprising that complicated patients have more longer recovery and inclreased fatigue, anxiety and
insomnia (some of it is related to mediction etc) hence their should be a breakdown of the results by
presence or absence of complications following transplant (ex: Clavien Dindo grade III or above)
Response: It is really true as Reviewer suggested that we should provide the data of indications,
MELD scores and post transplant status of our patients, however, we had not measured. We added
the following statement in Limitations, “Also, we did not report LT recipients’ indications, MELD scores
Downloaded from http://bmjopen.bmj.com/ on June 14, 2017 - Published by group.bmj.com
and post-transplant status which might be associated with their fatigue. More influencing factors, such
as recipients’ ...... primary disease diagnosis, and pre-transplant and post-transplant status should be
considered and explored in the future research..”
05. Please consider changing the terminology "fatigue now" and "fatigue in the last week" that have
been used throughout the manuscript. These should be referred to te point of assessment, perhaps
could be termed as "fatigue at the point of assesment" and "the week prior to assesment"
respectively.
Response: We have made correction according to the Reviewer’s comments.
Special thanks for your good comments. We appreciate for Editors /Reviewers’ warm work earnestly,
and hope that the correction will meet with approval. Once again, thank you very much for your
comments and suggestions.
VERSION 2 – REVIEW
REVIEWER
REVIEW RETURNED
Weng, Li-Chueh
Chang Gung University, Taiwan
20-Sep-2016
GENERAL COMMENTS
Authors has been revised the manuscript according my suggestions.
One more minor suggestion is:
Page 4, line 33-37, “Physiological factors included recipients’ age,
gender, BMI, duration after LT, and insomnia...”. Actually, these
variables did not fulfill the concept of physiological factors. It should
need to revise, such as “demographic factors”. The variables
“insomnia” may be suitable if it move to psychological factor.
REVIEWER
Mr. Thamara Perera FRCS
The Liver Unit,
Queen Elizabeth Hospital Birmingham
Birmingham
United Kingdom
20-Sep-2016
REVIEW RETURNED
GENERAL COMMENTS
Authors have revised the manuscript substantialy taking in to
consideration my previous comments, and the manuscript is
significantly improved in the current version.
VERSION 2 – AUTHOR RESPONSE
Reviewer: 1
Reviewer Name : Weng, Li-Chueh
Comments:
1. Page 4, line 33-37, “Physiological factors included recipients’ age, gender, BMI, duration after LT,
and insomnia...”. Actually, these variables did not fulfill the concept of physiological factors. It should
need to revise, such as “demographic factors”. The variables “insomnia” may be suitable if it move to
psychological factor.
Response: As Reviewer suggested that it is suitable to move “insomnia” variables to psychological
factor, we have made correction according to the Reviewer’s comments. Our study used the theory of
Downloaded from http://bmjopen.bmj.com/ on June 14, 2017 - Published by group.bmj.com
unpleasant symptoms to classify all variables, and the theory asserts three categories of factors
influencing patient’s symptom experience: physiological factors, psychological factors, and situational
factors, and they defined anatomical/structural, physiological, genetic, illness-related, and treatmentrelated variables as physiological factors, so we kept this naming and explained that they belone to
demographic information in quetionnaire introduction part.
Special thanks to you for your good comments!
Reviewer: 2
Reviewer Name : Mr. Thamara Perera MBBS, MS, FEBS, MD, FRCS
Comments:
Authors have revised the manuscript substantialy taking in to consideration my previous comments,
and the manuscript is significantly improved in the current version.
Special thanks for your good comments.
We appreciate for Editors /Reviewers’ warm work earnestly, and once again, thank you very much for
your comments and suggestions.
Downloaded from http://bmjopen.bmj.com/ on June 14, 2017 - Published by group.bmj.com
Fatigue and its associated factors in liver
transplant recipients in Beijing: a
cross-sectional study
Xiao-Hong Lin, Sha Teng, Lu Wang, Jing Zhang, Ya-Bin Shang,
Hong-Xia Liu and Yun-Jin Zang
BMJ Open 2017 7:
doi: 10.1136/bmjopen-2016-011840
Updated information and services can be found at:
http://bmjopen.bmj.com/content/7/2/e011840
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