We thank the reviewers for their insightful comments, which have helped us
improve the quality of this paper. Below are our point-by-point responses to the
comments.
Reviewer's report
Title: Depression and Medical Comorbidity Predict Suboptimal Improvement in
Knee Function after Total Knee Arthroplasty
Version:3Date: 28 December 2013
Reviewer:Emérito-Carlos RODRIGUEZ-MERCHAN
Reviewer's report:
MAJOR COMPULSORY REVISIONS
* The title should be changed: Depression in primary TKA and higher medical
comorbidities in revision TKA seem to be associated with suboptimal subjective
improvement in knee function
Response: We have changed the title as suggested. The new title is as follows:
“Depression in primary TKA and higher medical comorbidities in revision TKA are
associated with suboptimal subjective improvement in knee function”
* The way to define "depression" and "anxiety" is a great limitation of the article. Was
the diagnosis confirmed by a phychologist or phychiatrist?. If the answer is yes, the
paper is sound. If the answer is not, such a limitation makes the paper not sound (not
acceptable).
Response: Depression or anxiety was captured based on the presence of an ICD-9 code
code for these conditions, which is usually captured in patient records based on a health
care provider’s diagnosis. In most instances, this would be patients’ primary care provider
or family practitioner, rather than a psychiatrist, since most depression is managed in the
primary care setting in the U.S. We discussed this as a study limitation (see limitations
section).
We respectfully disagree that an absence of psychiatrist examination of a patient with
depression, makes this study not worthy of publication. The use of ICD-9 diagnoses in
epidemiological studies is not new, and has been done with its known limitations in both
non-arthroplasty and arthroplasty literature. A psychiatrist diagnosis of depression is most
ideal, but can’t be achieved in most epidemiological studies, given resource constraints
and the practical challenges of examining every patient. In retrospective analyses of
prospective data (as in our study) where psychiatrist referral for each patient had not been
done for each patient with ICD-9 for depression years prior to the study, this is not
possible. Even the well-funded cohort studies use validated questionnaires, due to issues
with resources. A Pubmed literature search of “depression” and “arthroplasty” (with both
in the title) done on 02/11/2014 found seven published studies, none of which used
psychiatrist diagnosis of depression: ICD-9 codes were used in 3 studies [1-3]; three used
depression scales [4-6]; and one used patient self-report [7]. Several studies published in
non-arthroplasty literature have used non-psychiatrist examination methods for
determining depression, e.g., validated depression questionnaires [8] or ICD-9 codes for
depression [9], supporting the belief that studies with imperfect measures of depression
can still contribute and help fill significant knowledge gaps. Again, we agree the best
method in prospective studies would be examination, but this criticism may not be
applicable to this retrospective cohort study. More importantly, the prevalence of
depression using our ICD-9 codes was similar to that reported in studies of depression
suing validated scales (see below).
Several novel findings of our study make it worthy of publication and of interest to the
readers. Our ability to include a large sample (5-10 times the highest sample in previous
studies) as well as perform multivariable-adjusted analyses makes our findings robust and
applicable, despite its limitations (which are listed in abstract, discussion and conclusions).
“Since both anxiety and depression were captured based on presence of a diagnostic
code, and psychological comorbidities may be under-recognized and under-diagnosed, it
is likely that we missed some cases; however, the prevalence of depression is similar to
the 9-15% reported in studies using validated instruments for depression [10-12]. This
might have biased our estimates towards null, and we may have missed some important
associations of anxiety and depression with outcomes. A retrospective study design did
not allow us to have confirmation of depression/anxiety diagnosis by examination by a
psychologist or a psychiatrist.”
* In the text the Deyo-Charlson index includes 19 morbidities, but in table 1 only
6 of them have been included. It seems logical to include all of them in the table.
Response: We have added all Deyo-Charlson index comorbidities in the table as
suggested, see table 1.
* In the ABSTRACT, in line 20 write depression and anxiety instead of physicological.
In lines 21 and 23 write TKA instead of THA. In line 24 mention that there are 19
medical comorbidities. In line 25 mention that knee function means much better-better
or same-worse. Also mention the great limitations of the study.
Response: We have made all the recommended changes and regret the typographical
errors. We have also added limitations to the abstract as suggested.
“Conclusions: Depression in primary TKA and higher medical comorbidity in revision TKA
cohorts were associated with suboptimal improvement in index knee function. Strategies
focused at optimization of medical comorbidities, anxiety and depression pre- and perioperatively may help to improve TKA outcomes. Study limitations include the use of
diagnostic codes, which may be associated with under-diagnosis of conditions and nonresponse bias.”
* My recommendation is that the authors should divide their article in four clear parts
(or articles): the relationship between depression and anxiety and subjective knee
function after primary TKA; and after revision TKA; and the relationship between
medical comorbidities and subjective knee after primary TKA; and after revision TKA.
As I mentioned above, depression and anxiety should be better defined and
diagnosed,
Response: We have divided our result into four sections, as per reviewer
recommendations.
“Depression, anxiety and Improvement in Knee Function after Primary TKA
At 2-years after primary TKA, 87% reported much better and 10% better knee
function compared to preoperatively, and at 5-years, 85% and 10%, respectively. At 2-year
follow-up, depression was associated with lower odds of much better knee function
(p<0.01) in univariate analyses (Appendix 2) as well as lower odds of 0.5 of much better
knee function (p=0.02) after multivariable-adjustment (Table 2). Anxiety was not
associated with subjective knee function improvement at 2-years (p≥0.50). At 5-years,
depression or anxiety were not significantly associated with knee function improvement
(Table 2).
Depression, anxiety and Improvement in Knee Function after Revision TKA
At 2-years after revision TKA, 65% reported much better knee function and 20%
better knee function compared to preoperatively, and at 5-years, 63% and 21%,
respectively. In univariate analyses at 5-years after revision TKA, depression was
associated with lower odds of much better knee function (p=0.05) (Appendix 3). In
multivariable-adjusted analyses, this was no longer significant (p=0.17; Table 2). At 5years, in multivariable-adjusted analyses, neither depression nor anxiety were associated
with knee function.
Medical Comorbidity and Improvement in Knee Function after Primary TKA
In univariate analyses, at 2-year follow-up, Deyo-Charlson index was associated
with a statistically non-significant trend with much better knee function (p=0.10) (Appendix
2). This was no longer significant after multivariable-adjustment, (p=0.47) (Table 2). At
5-years, Deyo-Charlson index was not significantly associated with knee function
improvement (p=0.25; Table 2).
Medical Comorbidity and Improvement in Knee Function after Revision TKA
In univariate analyses at 2 and 5-years after revision TKA, Deyo-Charlson had a
non-statistically significant association with much better knee function (p=0.50 and 0.13;
Appendix 3). In multivariable-adjusted analyses, higher Deyo-Charlson index was
associated with significantly lower odds of 0.5 of much better knee function (p=0.05; Table
2) and a trend towards significantly lower odds of 0.4 of better knee function (p=0.07;
Table 2) at 5-years. No significant associations were noted at 2-years (p>0.20).
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have not competing interest
Reviewer's report
Title:Depression and Medical Comorbidity Predict Suboptimal Improvement in
Knee Function after Total Knee Arthroplasty
Version:3Date: 1 February 2014
Reviewer:Shuji Taketomi
Reviewer's report:
The authors attempt to clarify whether medical and psychological comorbidity predicts
patient satisfaction after TKA, by analyzing a large sample. Interestingly, depression in
primary TKA and higher medical comorbidity in revision TKA cohorts were associated
with poor improvement in patient satisfaction.
Through the manuscript: “Knee function” after TKA usually means physical function
such as walking, climbing, bathing and so on), however, it is used as subjective
satisfaction in the manuscript. The use of the term “knee function” in this context may
be misleading.
Response: We have specified that this is subjective knee function assessment.
Introduction
Line 58: limitation(s)
Response: We have made this correction as suggested.
Methods
Lines 89-99: Selection of outcome of interest seems to be an issue. The authors
selected only “subjective” knee function evaluation as the outcome of interest. When
discussing knee function following TKA, we usually use both objective outcome (range
of motion, muscle strength, ###) and subjective outcome (KOOS, VAS, ###). The result
that depression was associated with subjective outcome (patient satisfaction) may be a
matter of course. Using not only subjective scale but also objective outcome scale may
add value to this study.
Response: We have specified that the function measure is subjective, by specifying this
in the title, abstract and other parts of the paper.
Line 112: [22][23,24] should be [22-24].
Response: We have made this change as recommended
Results
Lines 154-159: The authors state “patients were included in this study if they had
###completed the patient questionnaire”, however, they included all patients (7139
primary TKA###). It may be appropriate that the patient information of responders
is included at Table1.
Response: We clarified that we included patients who had responded to survey at
either 2- or 5-years. Non-responder characteristics are provided in Appendix 1,
which we have now presented as a table (table 2) according to the suggestion by
the reviewer. We considered combining it with Table 1, however this would make
table 1 uninterpretable and lead to 15 columns in the table and have several rows
that are applicable only to survey responders.
Line 156: “11” should be “Eleven”.
Response: We have made this change as recommended
Discussion
Lines 191-193: I think this sentence is stated at inappropriate location.
Response: We have made this change as recommended
Lines 194-200: The authors explain the factors which contributed the result from only the
point of view of rehab. In my opinion, subjective outcome of patients with depression
naturally differs from that of mentally-normal patients. If this result mainly depends on
rehabilitation, objective knee function should be different between the groups.
Additionally, why was not depression associated with poor patient satisfaction at 5-years
after TKA, vice versa at 2-years. Please discuss from these point.
Response: We agree and have added this to the discussion as recommended
“An interesting finding from our study was the association of depression with suboptimal
improvement in index knee function 2-years after primary TKA. Several factors may
contribute. Depressed patients are less likely to successfully complete rehabilitation
therapy [13, 14] that is required post-TKA. They may not follow-up with their surgeon
regularly due to concomitant depression and may have worse post-operative pain, which
may impact adherence with rehabilitation therapy. Optimal physical rehabilitation after
TKA is the key to best results after TKA [15, 16]. The absence of this association at 5years may be either due to a smaller sample size making it underpowered analysis or due
to “catching up” by patients with depression after 2-years.
Lines 221-222: If it is correct, why did the study of primary TKA result in a
different outcome from that of revision TKA?
Response: We discuss this in the discussion section.
“An interesting finding from our study was the association of depression with
suboptimal improvement in index knee function 2-years after primary TKA. Several factors
may contribute. Depressed patients are less likely to successfully complete rehabilitation
therapy [13, 14] that is required post-TKA. They may not follow-up with their surgeon
regularly due to concomitant depression and may have worse post-operative pain, which
may impact adherence with rehabilitation therapy. Optimal physical rehabilitation after
TKA is the key to best results after TKA [15, 16]. The absence of this association in
primary TKA at 5-years may be either due to a smaller sample size making it
underpowered analysis or due to “catching up” by patients with depression after 2-years.
The differences in findings between primary and revision TKA may be due to differences in
patient characteristics (depression, mean Deyo-Charlson index), the underlying diagnosis
and in the rate of complications between primary and revision TKA.”
Abstract
Line 21: “Total hip arthroplasty (THA)” should be “total knee arthroplasty (TKA)”. Line
23: “THA” should be “TKA”.
Line 26: Again, “THA” should be “TKA”.
Response: We regret these errors and have corrected them as recommended.
Lines 28-29: Comment is same for lines 154-159. Please see above.
Lines 35-38: These statements do not match with those of the conclusions section in
the context (Lines 251-254). I feel the contents in the context better reflect the study
results.
Response: We have modified and corrected these conclusions in the abstract.
“Conclusions: Depression in primary TKA and higher medical comorbidity in revision TKA
cohorts were associated with suboptimal improvement in index knee function. It remains
to be seen whether strategies focused at optimization of medical comorbidities and
depression pre- and peri-operatively may help to improve TKA outcomes. Study limitations
include the use of diagnostic codes, which may be associated with under-diagnosis of
conditions and non-response bias.”
Keywords
“Total knee arthroplasty” may be more appropriate than “total knee replacement”.
Response: We agree and have corrected this.
Level of interest:An article whose findings are important to those with closely related
research interests
Quality of written English:Acceptable
Statistical review:Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests.
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