Derek J. Roberts, MD, PhD
Assistant Professor, Department of Surgery, University of Ottawa
The Ottawa Hospital, Civic Campus
Room A-280, 1053 Carling Avenue
Ottawa, Ontario, Canada
K1Y 4E9
Tel.: 613-798-5555, Ext. 16268
Fax: 613-761-5362
Derek.Roberts01@gmail.com
Kanhaiya Singh, PhD
Academic Editor, PLoS One
May 14, 2021
RE: Disability, pain, and wound-specific concerns self-reported by adults at risk
of limb loss: A cross-sectional study using the World Health Organization Disability
Assessment Schedule 2.0
Dear Dr. Singh:
Re:
Ms. No.: PONE-D-21-10113
Ms. Title: Disability, pain, and wound-specific concerns self-reported by adults at
risk of limb loss: a cross-sectional study
We thank you and the PLoS One reviewers for the thoughtful reviews of our manuscript
and the opportunity to resubmit a revised version for consideration of publication
in PLoS One. We feel that our revised manuscript is an improved report, which we believe
addresses each of your and the Reviewer’s comments point by point. Please find below
an itemized list of detailed responses to each of your and the Reviewer’s comments,
including a description of the changes made to the revised version of the manuscript
(which are highlighted in yellow within the manuscript text). Within this itemized
list, we first cited each comment verbatim before providing our response for ease
of review.
**Comments from Dr. Singh:
1. Please ensure that your manuscript meets PLoS One’s style requirements, including
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Thank you for the kind and thoughtful review of our manuscript. We have ensured that
our manuscript meets PLoS One’s style requirements, including those for file naming,
as outlined in the style templates outlined above.
2. Please provide additional details regarding participant consent. In the ethics
statement in the Methods and online submission information, please ensure that you
have specified (i) whether consent was informed and (ii) what type you obtained (for
instance, written or verbal, and if verbal, how it was documented and witnessed).
If your study included minors, state whether you obtained consent from parents or
guardians. If the need for consent was waived by your ethics committee, please include
this information.
If you are reporting a retrospective study of medical records or achived samples,
please ensure that you have discussed whether all data were fully anonymized before
you accessed them and/or whether the IRB or ethics committee waived the requirement
for informed consent. If patients provided informed written consent to have data from
their medical records used in research, please include this information.
Thank you. We submitted the protocol for the study to the Ottawa Health Science Network
Research Ethics Board. Their review of the proposal indicated that the project fell
within the context of a quality initiative. Consequently, they stated that as per
the Tri-Council Policy Statement 2, Article 2.5, they waived the requirement for full
ethics approval and patient consent. The study did not include minors. In order to
better describe the above, we modified the “Design, objectives, and ethics” section
of the Materials and methods. This now reads:
“Design, objectives, and ethics
We conducted a cross-sectional study. After review of our ethics submission, The
Ottawa Health Science Network Research Ethics Board deemed that the study fell within
the context of a quality initiative and waived the need for full ethics approval and
patient consent. Reporting followed recommended guidelines [1,2].” (paragraph 1, page
6)
3. In ethics statement in the manuscript and in the online submission form, please
confirm that the IRB waived the need for full ethics approval.
Thank you. In the ethics statement in the manuscript and in the online submission
form, we have now confirmed that the IRB waived the need for full ethics approval
and patient consent (see above for a summary of the changes made to the Design, objectives,
and ethics section of the Material and methods section of the manuscript).
4. We note that you have indicated that data from this study are available upon request.
PLOS only allows data to be available upon request if there are legal or ethical restrictions
on sharing data publicly. For information on unacceptable data access restrictions,
please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions.
In your revised cover letter, please address the following prompts:
a) If there are ethical or legal restrictions on sharing a de-identified data set,
please explain them in detail (e.g., data contain potentially identifying or sensitive
patient information) and who has imposed them (e.g., an ethics committee). Please
also provide contact information for a data access committee, ethics committee, or
other institutional body to which data requests may be sent.
b) If there are no restrictions, please upload the minimal anonymized data set necessary
to replicate your study findings as either Supporting Information files or to a stable,
public repository and provide us with the relevant URLs, DOIs, or accession numbers.
Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For
a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories.
We will update your Data Availability statement on your behalf to reflect the information
you provide.
Thank you. The patients included in the study were those referred to a limb-preservation
clinic who were thought to be at risk of limb loss by both a specialty wound care
nurse and one of six vascular surgeons with extensive experience in limb-preservation.
Because these patients have a visibly uncommon outcome, the Medical Director of The
Ottawa Hospital limb-preservation clinic (Dr. S.K. Nagpal) and the Chief Innovation
and Quality Officer at The Ottawa Hospital (Dr. A.J. Forster) felt that their patient
information could not be sufficiently de-identified if it was presented on a non-summarized
level. Further, because their data are derived from routinely collected data generated
directly from clinical care, they are covered under Ontario’s health privacy legislation,
the Personal Health Information Protection Act (PHIPA). According to PHIPA, as we
are the custodians of these routinely collected data, we cannot make them openly available.
Instead, the legislation requires us, as the data custodians, to consider each request
on a case-by-case basis. Therefore, we had originally stated that we would provide
the data upon request to the principal author (Derek Roberts; Derek.Roberts01@gmail.com) because of the PHIPA. We hope that this explains why we had indicated that the data
would be provided upon request. We have also updated the above in the “Data Availability”
section of the manuscript submission and provided e-mail addresses for contact.
The PHIPHA Act states:
“Ontario’s health privacy legislation, the Personal Health Information Protection
Act (PHIPA), establishes a set of rules regarding personal health information
Health information custodians who have custody or control of your personal health
information are required to: designate or take on the role of a contact person to:
• help the custodian to comply with their obligations under PHIPA,
• ensure that agents of the custodian are appropriately informed of their duties,
• respond to inquiries from the public about their information practices,
• respond to your requests for access and corrections to your information,
• receive complaints about alleged breaches of PHIPA”
5. Additional Editor Comments:
Reviewers have found this study interesting however they are recommending discussion
of other confounding factors that may increase the risk of limb loss. Statistical
analysis was done appropriately. Was power of this study calculated? Please also address
the limitations of the present study.
Thank you. We agree with the Editor that many factors could influence an individual’s
disability state, including specific health conditions (in our case, the presence
of a lower extremity wound and/or their comorbidities), as well as social, economic
or environmental factors. While in the current study we did not have access to socioeconomic
or environmental factors (we assume the reviewer is likely referring to the built
environment, like housing and support?), we do acknowledge this in the limitations
section of the Discussion. Regarding comorbidities versus limb wounds, this was one
of our secondary objectives, and as reported in Table 2, patient characteristics (age,
sex, comorbidities) explained little of the variation in WHODAS disability scores
(~7%), whereas objective and patient-reported wound characteristics explained a substantial
amount (~40%). While this still leaves 60% to be explained, and we agree this could
be partly explained by socioeconomic and environmental factors, we do hope that the
reviewer agrees that we attempted to investigate these phenomena within the limitations
of the data available to us.
The power of the study was calculated a priori around the primary objective of estimating
the prevalence of clinically significant disability in our target population. Our
sample size was established to provide a precision of +/- 0.1 at the 5% significance
level around a clinically-postulated proportion of prevalent disability assumed to
be approximately 0.5. We estimated this to require 100 participants. However, as clinic
referrals were high and data collection feasible, we collected data from study start
until April 30, 2019 (the duration of time our quality improvement coordinator was
available for the study). This is described on page 9 of the revised version of the
manuscript. We have also included a limitations paragraph in the Discussion of the
revised manuscript. This paragraph now reads:
“Our findings need to be considered in the context of the study’s limitations. First,
we included patients referred to our limb-preservation clinic who were assessed to
be at risk of limb loss by an experienced PhD (wound care)-trained specialist wound
care nurse and vascular surgeon. Although the baseline characteristics of these patients
appeared characteristic of patients at risk of limb loss, the Society for Vascular
Surgery (SVS) Wound, Ischemia, foot Infection (SVS WIfI) classification system may
have provided an additional objective assessment of the risk of limb loss among those
with arterial-insufficient and diabetic wounds. However, the SVS WIfI was not designed
for use in patients with other types of hard-to-heal wounds (e.g., chronic venous
or postoperative wounds). Further, we lacked patient racial and economic data and
some of those included in our study did not have arterial pressure measurements required
to stratify patients into SVS WIfI stages at their first clinic assessment. Second,
while our patients found the WHODAS 2.0 to be clinically acceptable, they did require
assistance to input scores into a tablet. Future studies should therefore assess whether
findings would be similar when collected via patient-facing data entry. Third, while
it may be argued that a number of generic quality of life and disease-specific instruments
already exist for assessing PROs in patients at risk of limb loss, the WHODAS 2.0
has been extensively validated, displays broad applicability across those at risk
of limb loss, and when combined with measures of wound-specific concerns and discomfort/distress
captures all of the domains covered by these other instruments. It also allows for
direct comparison between other patient populations and studies of disability. Finally,
while the WHODAS 2.0 is widely validated across disease states and demonstrated promising
predictive validity in this study, our evaluation did not assess all aspects of validity.
Future studies should therefore assess concurrent and convergent validity and perform
longitudinal follow-up to determine reliability.” (paragraph 2, page 23-24)
***Reviewers’ comments:
Reviewer #1: Ref: PONE-D-21-10113: needs Major revisions.
In the present article entitled “Disability, pain, and wound-specific concerns self-reported
by adults at risk of limb loss: a cross-sectional study” Roberts, DJ et al., have
estimated the burden of disability in patient-reported outcomes (PROs) in patients
at risk of limb loss using the World Health Organization Disability Assessment Schedule
2.0 (WHODAS 2.0).
Although the manuscript contains a good amount of work, I have several concerns about
the manuscript in its current form. Here are the specific comments.
We thank the Reviewer for their kind and thoughtful review of our manuscript. The
comments have improved the study and are greatly appreciated.
1. Title: “WHODAS” maybe missing > may consider using WHODAS in second part of title
instead of describing the methodology here.
We agree. We have therefore added the World Health Organization Disability Assessment
Schedule to the second part of the title of the manuscript as suggested by the Reviewer.
The revised title of the manuscript is:
“Disability, pain, and wound-specific concerns self-reported by adults at risk of
limb loss: a cross-sectional study using the World Health Organization Disability
Assessment Schedule 2.0”
2. Review of literature: Novelty concerns: a systematic review done recently by “Mundy
et al.” clearly establishes an unmet need in the area, so this manuscript adds little
in terms of providing a solution to the existing literature. Mundy LR, Grier AJ, Weissler
EH, Carty MJ, Pusic AL, Hollenbeck ST, Gage MJ. Patient-reported Outcome Instruments
in Lower Extremity Trauma: A Systematic Review of the Literature. Plast Reconstr Surg
Glob Open. 2019 May 3;7(5):e2218. doi: 10.1097/GOX.0000000000002218. PMID: 31333950;
PMCID: PMC6571285.
We thank the Reviewer for highlighting the above systematic review of patient-reported
instruments in lower extremity trauma, and apologize if we do not understand the concerns
regarding novelty. In the above systematic review, the authors sought to identify
and evaluate patient-reported outcome (PRO) instruments developed specifically for
lower extremity trauma that were applicable to both lower extremity reconstruction
and amputation. These authors searched for English-language publications that described
the development and/or validation of a PRO instrument assessing satisfaction and quality
of life in lower extremity trauma patients. After reviewing 6,290 abstracts and 657
full-text citations, the authors were unable to identify any relevant studies. Therefore,
they suggested that there was a need for a PRO instrument to better understand those
with limb-threatening trauma.
We agree with the authors of this systematic review that there is no widely accepted
instrument for assessing PROs in a generic or disease-specific manner across patients
at risk of limb loss [3-5]. While we did not aim to evaluate those with lower extremity
trauma (and no patients with lower extremity trauma were included in our study), our
study did include those who are most commonly at risk of limb loss (i.e., those with
arterial-insufficient, diabetic, and other types of hard-to-heal wounds) [6-10]. We
hypothesized that the WHODAS 2.0 would be acceptable to patients at risk of limb loss
when administered in a clinic setting and would allow for quantification of the prevalence
and severity of disability among these patients. We also hypothesized that the WHODAS
2.0 would provide unique patient-important information above that provided by characteristics
of these patients and their wounds as well as a direct comparison of the degree of
disability to those with other medical and surgical conditions.
To our knowledge, our study is novel as it is the first to study disability among
patients at risk of limb loss using the WHODAS 2.0. This statement is supported by
the findings of a recent systematic review of the economic and humanistic burden of
hard-to-heal wounds by Ollson et al. in 2018 [6]. We found that the majority of people
at risk of limb loss suffered a substantial burden of disability. Most of them also
expressed concern over their wounds and suffered a moderate amount or great deal of
wound-related discomfort or distress. The WHODAS 2.0 displayed excellent clinical
acceptability among the included patients as well as evidence of criterion validity.
Our study therefore has important implications for practice and future research. First,
it suggests that the WHODAS 2.0 provides important patient-centered information among
patients at risk of limb loss. Second, as the tool has been shown to be a clinically
acceptable, valid, reliable, and responsive instrument for measuring disability across
a variety of chronic surgical [11-15] and medical [16-19] conditions, our results
suggest that measuring disability with this tool permits a direct comparison with
those with other medical conditions.
3. Abstract: The result paragraph is not scientifically developed. Can it be explained
in a more lucid manner? Example: well connected sentences.
Thank you. We reviewed the results paragraph of the Abstract and ensured that it was
scientifically developed and explained with well-connected sentences. The revised
Abstract is listed below, which has been extensively edited in direct response to
the above comment by the Reviewer. We feel that the Abstract now has well-connected
sentences while still being concise and following PLoS One’s instructions for authors
(the Abstract word limit for the Journal is 300 words). However, should the Reviewer
or Editor wish that we modify any of the remaining sentences, we would be more than
happy to do so.
“Abstract
Introduction: There has been limited study of patient-reported outcomes (PROs) in
patients at risk of limb loss. Our primary objective was to estimate the prevalence
of disability in this patient population using the World Health Organization Disability
Assessment Schedule 2.0 (WHODAS 2.0).
Materials and methods: We recruited patients referred to a limb-preservation clinic.
Patients self-reported their disability status using the 12-domain WHODAS 2.0. Severity
of disability in each domain was scored from 1=none to 5=extreme and the total normalized
to a 100-point scale (total score ≥25=clinically significant disability). We also
asked patients about wound-specific concerns and wound-related discomfort or distress.
Results: We included 162 patients. Reasons for clinic referral included arterial-insufficient
(37.4%), postoperative (25.9%), and mixed etiology (10.8%) wounds. The mean WHODAS
2.0 disability score was 35.0 (standard deviation=16.0). One-hundred-and-nineteen
(73.5%) patients had clinically significant disability. Patients reported they had
the greatest difficulty walking a long distance (mean score=4.2), standing for long
periods of time (mean score=3.6), taking care of household responsibilities (mean
score=2.7), and dealing with the emotional impact of their health problems (mean score=2.5).
In the two-weeks prior to presentation, 87 (52.7%) patients expressed concern over
their wound(s) and 90 (55.6%) suffered a moderate amount or great deal of wound-related
discomfort or distress. In adjusted ordinary least squares regression models, although
WHODAS 2.0 disability scores varied with changes in wound volume (p=0.03) and total
revised photographic wound assessment tool scores (p<0.001), the largest decrease
in disability severity was seen in patients with less wound-specific concerns and
wound-related discomfort and distress.
Discussion: The majority of people at risk of limb loss report suffering a substantial
burden of disability, pain, and wound-specific concerns. Research is needed to further
evaluate the WHODAS 2.0 in a multicenter fashion among these patients and determine
whether care and interventions may improve their PROs.”
4. Table 1: Personal characteristics or Demographics, line 219. Racial/economic disparities
could have been addressed.
We unfortunately did not collect patient racial and economic data. These data are
not routinely collected in how2trak or our hospital electronic medical record. However,
as we agree with the Reviewer that these data may have added additional important
information about the patients included in the study, we have added this as a limitation
of the study in the limitations section of the manuscript. The limitations section
of the manuscript now reads:
“Our findings need to be considered in the context of the study’s limitations. First,
we included patients referred to our limb-preservation clinic who were assessed to
be at risk of limb loss by an experienced PhD (wound care)-trained specialist wound
care nurse and vascular surgeon. Although the baseline characteristics of these patients
appeared characteristic of patients at risk of limb loss, the Society for Vascular
Surgery (SVS) Wound, Ischemia, foot Infection (SVS WIfI) classification system may
have provided an additional objective assessment of the risk of limb loss among those
with arterial-insufficient and diabetic wounds. However, the SVS WIfI was not designed
for use in patients with other types of hard-to-heal wounds (e.g., chronic venous
or postoperative wounds). Further, we lacked patient racial, economic, housing, and
external social and financial support data, and some of those included in our study
did not have arterial pressure measurements required to stratify patients into SVS
WIfI stages at their first clinic assessment. Second, while our patients found the
WHODAS 2.0 to be clinically acceptable, they did require assistance to input scores
into a tablet. Future studies should therefore assess whether findings would be similar
when collected via patient-facing data entry. Third, while it may be argued that a
number of generic quality of life and disease-specific instruments already exist for
assessing PROs in patients at risk of limb loss, the WHODAS 2.0 has been extensively
validated, displays broad applicability across those at risk of limb loss, and when
combined with measures of wound-specific concerns and discomfort/distress captures
all of the domains covered by these other instruments. It also allows for direct comparison
between other patient populations and studies of disability. Finally, while the WHODAS
2.0 is widely validated across disease states and demonstrated promising predictive
validity in this study, our evaluation did not assess all aspects of validity. Future
studies should therefore assess concurrent and convergent validity and perform longitudinal
follow-up to determine reliability.” (paragraph 2, page 23-24)
5. Fig2: data representation can be better; may be a pie-diagram wound be easier to
interpret here as compared to bar.
We agree. In direct response to the above suggestion by the Reviewer, we therefore
changed Fig. 2 from a bar diagram to a pie-diagram.
6. While it is not a standard practice, NIH prefers scatter diagrams in the current
grant guidelines as opposed to bar.
Thank you for this comment. Fig. 3 could potentially be displayed as a scatter diagram
while we do not believe that Fig. 4 could (the data are dichotomous so a scatter diagram
would just show two dichotomous areas of bubbles representing the values “yes” and
“no”). However, as there are 12 different variables displayed in the plot in Fig.
3, we would respectfully argue that the number of scatter bubbles would make the plot
rather busy and difficult for readers to easily comprehend. Further, in our utilized
statistical software (Stata), scatter plots can only be created as a twoway (y, x)
plot that compares the relationship between two continuous or measured variables.
We therefore elected to keep the bar diagram presented in the first version of the
manuscript. However, if the Reviewer or Editor feel strongly about using a scatter
instead of bar diagram for Fig. 3, we can submit this using an alternate statistical
software program.
7. The inherent limitations of using a WHODAS scale such as bodily impairments and
environmental factors have not been addressed. What has been done to address the high
prevalence of co-morbid conditions in the study population or does WHODAS inherently
address it?
Thank you for this comment. We hope that in responding we are properly interpreting
the Reviewer’s comment. As a patient-reported outcome, the WHODAS allows quantification
of the impact of a patient’s health state on their day to day function (or conversely,
their degree of disability) using 12 domains that are highly relevant to patients
and which are directly informed and linked to concepts in the International Classification
of Functioning, Disability and Health (ICF). This means that the impact of health
conditions can be quantified in a meaningful way without interpretation by a clinician
or researcher. Therefore, we understand the greatest value in using the WHODAS 2.0
to be the ability to measure a patient’s self-reported disability status directly.
However, we agree with the reviewer that many factors could influence an individual’s
disability state, including specific health conditions (in our case, the presence
of a lower extremity wound and/or their comorbidities), as well as social, economic
or environmental factors. While in the current study we did not have access to socioeconomic
or environmental factors (we assume the reviewer is likely referring to the built
environment, like housing and support?), we do acknowledge this in the limitations
section of the Discussion. Regarding comorbidities versus limb wounds, this was one
of our secondary objectives, and as reported in Table 2, patient characteristics (age,
sex, comorbidities) explained little of the variation in WHODAS disability scores
(~7%), whereas objective and patient-reported wound characteristics explained a substantial
amount (~40%). While this still leaves 60% to be explained, and we agree this could
be partly explained by socioeconomic and environmental factors, we do hope that the
reviewer agrees that we attempted to investigate these phenomena within the limitations
of the data available to us.
8. WHODAS basically gives a qualitative scale 1-5; none, mild, moderate, severe, extreme.
This is a subjective scale, is there be a more objective parameter to complement these
data?
The WHODAS 2.0 collects measures of disability that are self-reported by the patient.
The instrument uses 5-point scales to help to quantify the impact of each of the assessed
domains on an individual’s disability. Furthermore, as a patient-reported outcome
there is no need for this to be ‘filtered’ by the clinical team, meaning that these
patient-reported outcome measures inform patients, clinicians, and policy-makers about
how patients feel or function in relation to their health condition or conditions
without interpretation by healthcare providers.
While one could interpret this as subjective, we would also like to point to the psychometrics
reported from the development of this instrument (which are provided by Ustun and
colleagues [20]). These data demonstrate that the WHODAS 2.0 was found to have high
internal consistency (Cronbach’s alpha, α: 0.86), a stable factor structure; high
test-retest reliability (intraclass correlation coefficient: 0.98); good concurrent
validity in patient classification when compared with other recognized disability
measurement instruments; conformity to Rasch scaling properties across populations,
and good responsiveness (i.e. sensitivity to change). In other words, it does appear
that this approach to measuring disability in a quantitative but patient-reported
manner is likely numerically valid.
Finally, in our study, these data appeared to provide unique patient-important information
above standard clinical information as WHODAS 2.0 disability scores were only moderately
correlated with objective wound criteria and were not entirely explained by wound
and patient characteristics. Therefore, while we agree that a patient’s experience
of disability is subjective, when measured with this instrument they do appear to
provide additional patient-important information above that provided by standard objective
measures.
9. Will it be more prudent to follow up the patients since it is a well-established
limb salvage clinic and look at the change in WHODAS (change WHODAS 2.0) with intervention
as compared to a cross-sectional study?
We agree. As a follow up to the current cross-sectional study, we recently initiated
a prospective cohort study of patients at risk of limb loss (using the same criteria
as the current study). This study compares changes in WHODAS 2.0 disability scores
with measures of wound healing to determine if advanced wound care in our limb preservation
clinic and program improves patients’ estimated disability. In order to outline these
next research steps better for readers, we modified the Conclusion section of the
manuscript. This now reads:
“Conclusions
In this cross-sectional study, we found that the majority of people at risk of limb
loss suffered a substantial burden of disability. Most of them also expressed concern
over their wounds and suffered a moderate amount or great deal of wound-related discomfort
or distress. The WHODAS 2.0 displayed excellent clinical acceptability among the included
patients as well as evidence of criterion validity. Therefore, it may provide additional
important patient-centered information among patients at risk of limb loss. Future
studies should further validate the instrument in a multicenter fashion. They should
also determine how care and interventions (e.g., to enhance wound healing) provided
over time to these patients may decrease their burden of disability, pain, and wound-specific
concerns.” (page 24)
10. Limb loss is a major concern in terms of economic burden and also is a life-altering
event. Hence I strongly encourage the authors to further work on this manuscript and
I will be happy to provide further inputs. Looking forward to your reply to these
queries and hopefully this helps in improving the work.
Respectfully,
Reviewer
We thank you for your kind and thoughtful comments on our work. They have improved
our manuscript and are greatly appreciated.
Reviewer #2: Ref: PONE-D-21-10113
In the present article entitled “Disability, pain, and wound-specific concerns self-reported
by adults at risk of limb loss: a cross-sectional study” Roberts et al., have estimated
the burden of disability in patient-reported outcomes (PROs) in patients at risk of
limb loss using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS
2.0). While the data collection and WHODAS 2.0 application appear sound to me, here
are specific comments.
We thank the Reviewer for their kind and thoughtful review of our manuscript. The
comments have improved the study and are greatly appreciated.
1. Title can be made more precise and inclusion of WHODAS 2.0 to it can make it more
apt.
We agree. We have therefore added the World Health Organization Disability Assessment
Schedule to the title of the manuscript as suggested by the Reviewer. The revised
title of the manuscript is:
“Disability, pain, and wound-specific concerns self-reported by adults at risk of
limb loss: a cross-sectional study using the World Health Organization Disability
Assessment Schedule 2.0”
2. Introduction: secondary objectives which were to determine the clinical acceptability
of WHODAS 2.0, and to look for the extent to which various patient and wound characteristics
can predict the degree of disability, can be included in the introduction.
We agree with the Reviewer that the primary and secondary objectives of the study
should be explicitly stated in the Introduction section of the manuscript. In direct
response to the above suggestion by the Reviewer, we therefore included both the study
hypotheses and objectives in the final paragraph of the Introduction. This paragraph
now reads:
“Given its broad validity, we hypothesized that the WHODAS 2.0 would be acceptable
to patients at risk of limb loss when administered in a clinic setting and would allow
for quantification of the prevalence and severity of disability among these patients.
We also hypothesized that the WHODAS 2.0 would provide unique patient-important information
above that provided by characteristics of these patients and their wounds as well
as a direct comparison of the degree of disability to those with other medical and
surgical conditions. The primary objective of the study was to estimate the prevalence
and severity of disability in patients at risk of limb loss using the WHODAS 2.0.
Secondary objectives were to determine whether the WHODAS 2.0 was clinically acceptable
to these patients and the extent to which patient and wound characteristics, wound-specific
concerns, and wound-related discomfort or distress predicted their disability.” (paragraph
2, page 5)
3. Materials and methods: the patients recruited in this study were thought to be
at the risk of limb loss. This can be elaborated further so as to mark if any objective
criteria were followed to consider the probability of limb loss.
Thank you. We included patients referred to our limb-preservation clinic who were
assessed to be at risk of limb loss by an experienced PhD (wound care)-trained specialist
wound care nurse and vascular surgeon because there is no well-validated instrument
for assessing risk of limb loss among patients with different wound types. The Society
for Vascular Surgery (SVS) Wound, Ischemia, foot Infection (SVS WIfI) classification
system may have provided an additional objective assessment of the risk of limb loss
among those with arterial-insufficient and diabetic wounds. However, the SVS WIfI
was not designed for use in patients with other types of hard-to-heal wounds, including
those that were included in this study (e.g., chronic venous or postoperative wounds).
In order to make this clear for readers, the Participants section of the Methods reads:
“Participants
There is no well-validated instrument for assessing risk of limb loss among patients
with different wound types aside from arterial-insufficient and diabetic foot wounds.
We therefore included consecutive adults (age >18-years) referred to TOH Limb-Preservation
Clinic starting in June 1, 2018 thought to be at risk of limb loss by both the specialty
wound care nurse and one of six vascular surgeons with extensive experience in limb-preservation.
A vascular surgeon first evaluated all patients before they were seen in clinic. Our
goal was to recruit a diverse cohort of patients with hard-to-heal wounds at risk
of limb loss.” (paragraph 3, page 7-8)
We also acknowledge the above as a potential limitation in the limitations section
of the Discussion. This limitations section reads:
“Our findings need to be considered in the context of the study’s limitations. First,
we included patients referred to our limb-preservation clinic who were assessed to
be at risk of limb loss by an experienced PhD (wound care)-trained specialist wound
care nurse and vascular surgeon. Although the baseline characteristics of these patients
appeared characteristic of patients at risk of limb loss, the Society for Vascular
Surgery (SVS) Wound, Ischemia, foot Infection (SVS WIfI) classification system may
have provided an additional objective assessment of the risk of limb loss among those
with arterial-insufficient and diabetic wounds. However, the SVS WIfI was not designed
for use in patients with other types of hard-to-heal wounds (e.g., chronic venous
or postoperative wounds). Further, we lacked patient racial and economic data and
some of those included in our study did not have arterial pressure measurements required
to stratify patients into SVS WIfI stages at their first clinic assessment. Second,
while our patients found the WHODAS 2.0 to be clinically acceptable, they did require
assistance to input scores into a tablet. Future studies should therefore assess whether
findings would be similar when collected via patient-facing data entry. Third, while
it may be argued that a number of generic quality of life and disease-specific instruments
already exist for assessing PROs in patients at risk of limb loss, the WHODAS 2.0
has been extensively validated, displays broad applicability across those at risk
of limb loss, and when combined with measures of wound-specific concerns and discomfort/distress
captures all of the domains covered by these other instruments. It also allows for
direct comparison between other patient populations and studies of disability. Finally,
while the WHODAS 2.0 is widely validated across disease states and demonstrated promising
predictive validity in this study, our evaluation did not assess all aspects of validity.
Future studies should therefore assess concurrent and convergent validity and perform
longitudinal follow-up to determine reliability.” (paragraph 2, page 23-24)
4. Data collection, methods of measurement, and definitions: Limb ischemia is one
of the presentations of various systemic diseases like Diabetes, Atherosclerosis,
Aortoarteritis, end stage renal disease and a few more. Various other presentations
and symptoms of these systemic illnesses can act as confounding factors while patients
respond to the WHODAS 2.0 questionnaire. So this aspect of confounding factors needs
to be addressed further.
Thank you for this comment. First, we just hope to clarify the context of the Reviewer’s
comment. Specifically, at least in our understanding, a confounder is a variable that
influences both the likelihood of an exposure or intervention being present, while
also being associated with likelihood of outcome. In the current study, we have not
evaluated a specific exposure or intervention in relation to our outcome (WHODAS 2.0
disability score), but instead look to understand what variables may be explanatory
(or perhaps predictive, although we are not trying to build a clinical prediction
model) of disability.
Within this context, we agree that we did not have all possible explanatory or predictive
variables available to us. However, we did find that when considering only a patient’s
baseline measured covariates (age, sex, comorbidities) we were unable to explain much
of the variation in observed disability scores (7%). In contrast, when we looked at
objective and self-reported wound specific variables we were able to explain a moderate
amount of variation (40%).
Ultimately we agree that this leaves much variation to be explained, and we now further
highlight the limitations in our available measured variables and point to the need
for further, prospective and multicenter evaluation.
5. Discussion paragraph can be further delineated in an intelligible manner to improve
the flow.
Thank you. We have reviewed the Discussion of the manuscript in detail and modified
this after critical input by each of our coauthors to ensure it is delineated in an
intelligible manner to improve the flow. We are wondering if you perhaps specifically
are referring to the 1st paragraph of the discussion? Please see the updates below.
We hope tha this is satisfactory, however, if the Reviewer or Editor have any further
suggestions to improve flow, we would be more than happy to make additional changes.
The first paragraph of the Discussion now reads:
“In this cross-sectional study of patients at risk of limb loss due to lower limb
wounds, we found that almost three-out-of-four suffered from clinically significant
disability. These patients had a number of different types of lower limb wounds, including
arterial-insufficient, mixed, postoperative, chronic venous, and diabetic wounds.
Further, over half of these patients expressed concerns over their wound(s) and suffered
a moderate amount or great deal of wound-related discomfort or distress. Importantly,
we found that the increasingly well-established clinical acceptability of the WHODAS
2.0 generalized to the older, comorbid patients routinely seen in a limb-preservation
clinic. Finally, the WHODAS 2.0 had evidence of providing unique patient-important
information as it was only moderately correlated with other patient-reported and objective
wound criteria, and was not entirely explained by wound and patient characteristics.”
(paragraph 1, page 21)
6. Authors have not discussed any limitations they faced or tackled during this study.
We apologize if the limitations section of the manuscript was not clearly identified.
We therefore revised the first sentence of the limitations section of the Discussion
such that it reads “Our findings need to be considered in the context of the study’s
limitations.” This limitations paragraph now reads:
“Our findings need to be considered in the context of the study’s limitations. First,
we included patients referred to our limb-preservation clinic who were assessed to
be at risk of limb loss by an experienced PhD (wound care)-trained specialist wound
care nurse and vascular surgeon. Although the baseline characteristics of these patients
appeared characteristic of patients at risk of limb loss, the Society for Vascular
Surgery (SVS) Wound, Ischemia, foot Infection (SVS WIfI) classification system may
have provided an additional objective assessment of the risk of limb loss among those
with arterial-insufficient and diabetic wounds. However, the SVS WIfI was not designed
for use in patients with other types of hard-to-heal wounds (e.g., chronic venous
or postoperative wounds). Further, we lacked patient racial, economic, housing, and
external social and financial support data, and some of those included in our study
did not have arterial pressure measurements required to stratify patients into SVS
WIfI stages at their first clinic assessment. Second, while our patients found the
WHODAS 2.0 to be clinically acceptable, they did require assistance to input scores
into a tablet. Future studies should therefore assess whether findings would be similar
when collected via patient-facing data entry. Third, while it may be argued that a
number of generic quality of life and disease-specific instruments already exist for
assessing PROs in patients at risk of limb loss, the WHODAS 2.0 has been extensively
validated, displays broad applicability across those at risk of limb loss, and when
combined with measures of wound-specific concerns and discomfort/distress captures
all of the domains covered by these other instruments. It also allows for direct comparison
between other patient populations and studies of disability. Finally, while the WHODAS
2.0 is widely validated across disease states and demonstrated promising predictive
validity in this study, our evaluation did not assess all aspects of validity. Future
studies should therefore assess concurrent and convergent validity and perform longitudinal
follow-up to determine reliability..” (paragraph 2, page 23-24)
Thank you once again for the reviews. The comments provided by Dr. Singh and the Reviewers
have improved our manuscript. We hope that you will find this version suitable for
publication in PLoS One, and look forward to your response.
Sincerely,
Derek J. Roberts, MD, PhD and Daniel I. McIsaac, MD, MPH
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