Evidence-based practice involves finding the best research evidence to support an intervention, which is integrated with patient preferences and values and professional expertise, and then implemented. Once you have searched and found relevant and timely research studies, the next step is to evaluate the quality of their methods, design, and other elements and to explore the application of the evidence they provide in different scenarios and settings. It is of paramount importance to correctly identify the type of research methods used in the study—quantitative or qualitative, or a mixture of both—and to evaluate the study to ensure those methods are high-quality, valid, reliable, and accurate. Consequently, doctoral professionals must develop a working knowledge of how to identify and critically appraise specific, important elements of both quantitative and qualitative research studies. Rapid critical appraisal tools assist in developing this skill.
Dorleijn, D. M. J., Luijsterburg, P. A. J., Reijman, M., Kloppenburg, M., Verhaar, J. A. N., Bindels, P. J. E., . . . Bierma-Zeinstra, S. (2018). Intramuscular glucocorticoid injection versus placebo injection in hip osteoarthritis: A 12-week blinded randomised controlled trial. Annals of the Rheumatic Diseases, 77(6), 875.
Howson, A., Turell, W., & Roc, A. (2018). Perceived self-efficacy in B-cell non-Hodgkin lymphomas: Qualitative outcomes in patient-directed education. Health Education Journal, 77(4), 430–443.
Rapid Critical Appraisal Questions for Randomized Controlled Trials (RCTs), page 711.
Rapid Critical Appraisal Questions for Qualitative Evidence, pages 715–716.
Note: Remember that you can submit all or a portion of your completed executive summary and both general overviews and critical appraisals to
Smarthinking
for feedback before you submit the final version for this assignment. If you plan on using this free service, be mindful of the turnaround time of 24–48 hours for receiving feedback.
Write a paper in which you:
Your document should be 4–5 pages in length, including the overviews, rapid critical appraisals, and executive summary.
Include at least two resources, other than the course textbook, to support your critical appraisals. Provide in-text citations and references in APA format for each study, the critical appraisal tools, and other resources used.
The following requirements correspond to the scoring guide criteria, so be sure to address each point. Read the performance-level descriptions in the scoring guide for each criterion to see how your work will be assessed.
Include the study’s purpose, methods, design, results, and any other aspects of the study you think are noteworthy.
Consider how the study contributes to the scholarly literature.
Create a table or other organized format for your answers to the questions on the RCA tool for each study.
What evidence supports your assertions and conclusions?
Consider the following questions to guide the comparison of these studies in your executive summary:
Which study provides the best overall evidence? What elements in the study led you to this conclusion?
Which study provides subjective information that could be integrated to make positive changes to services, processes, systems, or patient care?
What is the significance of each study’s results in a hospital setting? How do the results affect patients?
How could the evidence found in each study be applied in different health care settings? In the overall health care industry?
Public Healthgraduate
https://doi
.
org/10.1177/0017896918763232
Health Education Journa
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2018, Vol. 77(4) 430 –443
© The Author(s) 2018
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DOI: 10.1177/0017896918763232
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Perceived self-efficacy in B-cell
non-Hodgkin lymphomas:
Qualitative outcomes in patient-
directed education
Alexandra Howsona, Wendy Turellb
and Anne Rocb
aThistle Editorial, LLC, Snoqualmie, WA, USA
bPlatformQ Health Education LLC, Needham, MA, USA
Abstract
Objective: Perceived self-efficacy (PSE) is considered a foundation for effective self-care in the context of
chronic disease and illness. In order to improve patient and caregiver knowledge about self-care in B-cell
non-Hodgkin’s lymphoma (NHL), we designed and delivered an online, patient-focused education activity.
Educational impact on PSE was evaluated using a mixed quantitative/qualitative methodology. We report
here on the qualitative characteristics of self-efficacy
.
Methods: We interviewed participants using open-ended questions based on a semi-structured interview
guide. Interviews were audio-recorded and transcribed verbatim, and analysed using constant comparative
method with software support (NVivo for Mac 11, QSR International).
Results: In all, 12 people diagnosed with B-cell NHL were interviewed. Descriptive analysis showed that
participants were able to summarise key education messages about B-cell NHL presented in the programme.
Key themes linked to self-care knowledge and practice included normalisation of self-care, learning the
hard way, everyone is different and being prepared. Participants described four key strategies linked to the
notion of ‘being prepared’: (1) asking questions, (2) building relationships with oncologists, (3) developing/
maintaining a philosophy of life, and (4) connecting with others. These themes provide context for the
experience of PSE and may also reflect beliefs that have implications for self-efficacy educatio
n.
Conclusions: Interview data affirm PSE as a foundation of self-care and identify beliefs underpinning PSE.
A dominant belief of ‘being prepared’ was sustained by four strategies that education content reinforced.
Educators can use these insights to strengthen self-efficacy education interventions for patients with B-cell
NHL and other types of cancer.
Keyword
s
B-cell non-Hodgkin’s lymphoma, cancer, patient education, perceived self-efficacy, qualitative, self-care
Corresponding author:
Alexandra Howson, Thistle Editorial, LLC, 7021 Carmichael Ave SE, Snoqualmie, WA 98065, USA.
Email: alexhowson@thistleeditorial.com
763232 HEJ0010.1177/0017896918763232Health Education JournalHowson et al.
research-article2018
Original Article
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Howson et al. 431
Background
B-cell non-Hodgkin’s lymphoma (NHL) is a haematological disease with several subtypes and a
potentially chronic trajectory. Treatment depends upon the particular subtype, as well as stage of
the disease, and includes involved-site radiotherapy, chemotherapy, targeted therapies, and active
surveillance (American Cancer Society, 2017). While targeted therapies have improved prognosis,
and patients may live with their disease for several years, patients receiving a diagnosis of B-cell
NHL suffer from significant distress and poor quality of life, and require considerable supportive
care and education on the implications of their disease for treatment, treatment-related side effects,
and self-care (Mols et al., 2007; Oerlemans et al., 2011; Smith et al., 2013). Self-care education is
becoming increasingly necessary as many types of cancer, including B-cell NHL, evolve into
chronic conditions for which patients need extensive management over years or even decades
(American Cancer Society, 2016). Yet such education for patients with B-cell NHL is currently
limited in availability and scope. Indeed, a recent Dutch survey found that up to 43% of patients
with NHL lack credible information about diagnostic testing and treatment options, and 39% felt
there was a lack of guidance and support (Stienen et al., 2014).
The available evidence suggests that education on self-care strategies, such as communicating
with health professionals, goal-setting, and problem-solving, can help to reduce uncertainty for
patients, foster a sense of control over the experience of living with cancer, and buttress self-effi-
cacy (e.g. Boger et al., 2015; Kidd et al., 2009; McCorkle et al., 2011; Porter et al., 2008). Self-
efficacy is a core psychological concept used to predict and explain people’s motivations to take up
particular health behaviours, such as self-care. In models of behaviour change (e.g. the
Transtheoretical Stages of Change Theory; Prochaska and DiClemente (1982)), self-efficacy pre-
sumes rational action (Fishbein and Ajzen, 1975), and is typically measured as a predictor of future
behaviour following exposure to an educational programme or activity (Peterson, 2006). In the
context of health and illness, these theories posit that learning, action, and behaviour change are
influenced by self-beliefs derived from interactions between personal, environmental or situational
and behavioural determinant
s.
Perceived self-efficacy (PSE) is a corollary of self-efficacy that is considered a mediator between
the act or process of learning and the implementation of new knowledge or skills in a health context
(Williams et al., 2015). PSE refers to ‘beliefs in one’s capabilities to organise and execute the courses
of action required to manage prospective situations’ (Burke et al., 2009), which are influenced by a
range of behaviours, environmental factors and personal/cognitive characteristics (Prochaska and
DiClemente, 1982). Four sources of information are deemed especially crucial in the formation of
PSE beliefs: (1) previous performance or mastery experiences, (2) vicarious experiences from
observation and social comparison, (3) social persuasion (e.g. education messages) and (4) experi-
ences arising from physical and emotional states (e.g. anxiety). Positive experiences related to each
of these areas are believed to increase the likelihood of high levels of PSE (Peterson, 2006).
In order to support self-efficacy for patients living with B-cell NHL, PlatformQ Health
Education, LLC (PQH), in conjunction with the Leukemia and Lymphoma Society (LLS) and the
University of Nebraska Medical Centre (UNMC), launched an online patient and caregiver-centric
video programme to improve knowledge about B-cell NHL and offer strategies to enhance quality
of life through better disease and side effect management. We evaluated the impact of this educa-
tion on knowledge and self-efficacy via a mixed methods outcomes methodology. Following the
quantitative measurement of knowledge uptake, we also explored the impact of the educational
intervention on knowledge about and perspectives on B-cell NHL self-care and self-efficacy via
qualitative interviews with education participants. Here, we report on characteristics of self-effi-
cacy that emerged in analysis of qualitative outcomes.
432 Health Education Journal 77(4
)
Methods
Patient education programme design, delivery and evaluation of knowledge uptake
The education programme, Patient Education on B-Cell Non-Hodgkin Lymphomas from Diagnosis
to Treatment, consisted of one 60-minute session with 4 parts, each of which could be viewed in its
entirety or separately on http://www.cancercoachlive.com/. Programme design was directed by
findings from a comprehensive needs assessment that identified specific gaps in patient and car-
egiver knowledge about B-cell NHL. The programme featured insights from multiple sources and
patient vignettes and provided participants with a range of resources such as fact sheets and web
links to support organisations. The web-based activity was initially launched live and online on 4
August 2016, and was available on-demand for one year. The sessions were filmed in a production
studio with three faculty-panel members – an oncologist from the University of Nebraska Medical
Centre, the Executive Director of the Leukaemia and Lymphoma Society, and a nurse practitioner
from the Dana-Farber Cancer Institute, Boston, Massachussetts – who discussed the following
topics:
1. Understanding the diagnosis. What does it mean to have B-cell NHL?
2. The work-up. What tests to expect for B-Cell NHLs;
3. Treating B-cell NHLs;
4. What to do between doctor visits and treatments. Self-care, resources.
Patient participants were able to submit questions before and during the live programme, and
faculty answered a sampling of these questions throughout the 4 sessions. Live polling questions
regarding social support, treatment concerns and other relevant topics were also interspersed with
faculty discussions and question responses and integrated into the discussion flow. In total, 535
learners participated in the educational programme on cancercoachlive.com, and an additional
26,174 viewed the programme via social media channels (25,166 on Facebook and 1,008 on the
Leukaemia & Lymphoma Society YouTube Channel).
We evaluated trends in knowledge uptake associated with programme participation using Moore
et al.’s seven-level evaluation framework (Moore et al., 2015), up to outcomes level 6 (patient
impact). The goal of the outcomes plan was to (1) assess the degree to which the proposed initiative
facilitated positive knowledge and behaviour change, (2) assess the degree to which the proposed
initiative facilitated positive health-related self-efficacy and (3) gather information to help inform
and guide future education in this therapeutic area. We measured trends in knowledge uptake via
pre- and post-test online surveys that were administered to all activity participants before and
immediately following programme completion, as well as via an online follow-up survey distrib-
uted within 8 weeks of the activity completion dat
e.
Exploring patient knowledge of and perspectives on self-care
Qualitative data collection and analysis. In addition to quantitative evaluation of knowledge out-
comes, we explored the impact of the educational intervention on knowledge about and perspec-
tives on B-cell NHL self-care and self-efficacy via qualitative interviews with education
participants
We recruited potential interview participants 6–10 weeks following activity participation via
email. Participants were eligible to participate in interviews if they had (1) a confirmed diagnosis
of B-cell NHL, (2) currently resided in the USA and (3) recalled viewing the education programme.
We determined this eligibility via an invitation and screener emailed to programme participants.
Howson et al. 433
Those who did not meet the inclusion criteria were not invited to participate in interviews. When
screening for potential interviewees began, 183 participants had completed the education activity
(13 September 2016) and 37 responded to interview invitations. Of these 37 invitation respondents,
15 were eligible as per inclusion criteria and 3 did not respond to scheduling information. A small
honorarium was offered for completing an interview.
The interview topic guide (online supplementary file) was designed to explore patient
understandings of B-cell NHL symptoms, tests at diagnosis, treatment options and treatment-
related side effects, and self-care strategies via open-ended questions. One of the authors
(A.H.), a PhD-level trained medical sociologist, conducted these confidential, 30- to 45-min-
ute telephone interviews, which were scheduled at convenient times for participants. Western
Institutional Review Board granted ethical approval for the study, and we obtained informed
consent from all participants prior to interviews. None of the participants were personally
known to the authors.
We audio-recorded interviews via cloud-based, web-conferencing software (ww.uberconfer-
ence.com), transcribed interviews verbatim and imported them into NVivo for Mac (QSR
International), a software package designed to support systematic analysis of unstructured data.
We used a process of constant comparison to structure analysis of participant responses to ques-
tions both across interviews and within interviews (Corbin and Strauss, 2015). This approach
included three components: (1) data immersion and familiarisation, (2) descriptive data coding
and (3) thematic coding (Saldaña, 2013). One of the authors (A.H.) initially coded transcript
content into descriptive categories that broadly followed the structure and focus of the interview
categories concerning the education activity impact on self-reported knowledge and behaviour.
Following descriptive coding, a second round of coding identified themes across the dataset until
thematic saturation was achieved. These themes were further explored for connections and rela-
tionships (Roller and Lavrakas, 2015). The principal investigator (W.T.) corroborated the analy-
sis to ensure it reflected the study aim, which, as stated above, was to explore the impact of the
educational intervention on knowledge about and perspectives on B-cell NHL self-care and
self-efficacy.
Findings
Descriptive analysis: education impact on knowledge
We interviewed 12 people with a diagnosis of B-cell NHL, aged between 43 and 78 years, with a
mean age of 60 years (Figures 1 and 2).
Time from diagnosis ranged from 2 to 24 years prior to interview. As not all participants pro-
vided this information, we did not explore relationships between this attribute and descriptive or
emergent themes.
Descriptive analysis showed that participants demonstrated prior knowledge about topics cov-
ered in the learning objectives and were able to summarise key education messages about B-cell
NHL presented in the programme, including the broad approaches to, and benefits of, treatment
options and treatment-related side effects.
Participants generally felt that the education activity reinforced their understanding of B-cell
NHL and provided a ‘good way to learn more about the disease’. As one participant noted, ‘the
more you hear things and do things over and over, the better you get at you know explaining to
others’ (Patient 4). Participants also described a range of self-care strategies that were in line with
education messages, such as engaging in daily activity, eating well, getting rest, and having a posi-
tive mental attitude.
https://journals.sagepub.com/doi/suppl/10.1177/0017896918763232
434 Health Education Journal 77(4)
Thematic analysis: foundations of self-care knowledge and practice
Thematic analysis generated several themes linked to self-care knowledge and practice, includ-
ing normalisation of self-care, learning the hard way, everyone is different, and being prepared
(Table 1).
Normalisation of self-care. Participants were emphatic about the importance of engaging in self-care
practices as a normal or central part of their lives to maintain health/well-being.
It’s very important to get up and move for a lot of reasons. (Patient 7)
Try to get out of bed and take walks and just get out and not just stay under the covers like I did because
you’re going to feel bad no matter what. You might as well be part of life. (Patient 11)
I guess one of the things I can do for myself is to be aware of my diet, to eat really healthy and nutrition is
really important because what you take into your body really will help to maintain your immune system.
(Patient 9)
I found that you have to be in good spirits. You have to do your exercise. Your diet is very important.
(Patient 5)
Figure 1. Participant characteristics: age, gender and ethnicity.
Figure 2. Participant characteristics: region and B-cell type.
Howson et al. 435
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Le
uk
em
ia
L
ym
ph
om
a
So
cie
ty
I
tr
ul
y
go
t i
n
an
in
sid
e
he
lp
. I
w
ro
te
d
ow
n
a
se
rie
s
of
q
ue
st
io
ns
. I
o
rd
er
ed
th
e
bo
ok
le
t f
ro
m
th
e
na
tio
na
l o
ffi
ce
.
I
m
em
or
ise
d
th
at
n
on
-H
od
gk
in
’s
lym
ph
om
a
m
an
ua
l a
nd
I
m
ea
n
I h
ig
hl
ig
ht
ed
it
, I
r
ea
d
it,
I
m
em
or
ise
d
th
e
en
tir
e
bo
ok
.
As
k
as
m
an
y
qu
es
tio
ns
a
s
th
ey
c
an
li
ke
w
hy
it
’s
[t
re
at
m
en
t]
n
ec
es
sa
ry
.
I’m
a
v
er
y
an
al
yt
ica
l p
er
so
n
so
I’
ve
d
on
e
qu
ite
a
b
it
of
r
es
ea
rc
h
on
it
. D
on
’t
he
sit
at
e
to
a
sk
q
ue
st
io
ns
an
d
th
at
’s
pa
rt
o
f
w
ha
t I
e
nc
ou
ra
ge
p
at
ie
nt
s
th
at
a
re
g
oi
ng
th
ro
ug
h
th
at
.
436 Health Education Journal 77(4)
M
ai
n
T
he
m
es
(
N
um
be
r
of
c
od
in
g
re
fe
re
nc
es
+
it
em
s
co
de
d)
D
ef
in
iti
on
s
Ex
em
pl
ar
q
uo
te
Pa
rt
o
f i
t w
as
li
ke
, y
ou
k
no
w
, p
ut
tin
g
to
ge
th
er
a
s
pr
ea
ds
he
et
o
f p
as
sw
or
ds
o
f o
nl
in
e
pa
ym
en
ts
a
nd
th
in
gs
li
ke
th
at
, s
ha
rin
g
w
ith
p
eo
pl
e
an
d
se
nd
in
g
it
ou
t.
I’m
a
lw
ay
s
lo
ok
in
g
fo
r
an
y
in
fo
rm
at
io
n
th
at
I
ca
n
le
ar
n
m
or
e
ab
ou
t m
y
no
n-
H
od
gk
in
’s
lym
ph
om
a
an
d
I p
ar
tic
ip
at
e
in
s
ev
er
al
d
iff
er
en
t
m
et
ho
ds
a
nd
m
at
er
ia
ls
of
th
in
gs
th
at
w
he
ne
ve
r
ge
t a
c
ha
nc
e
to
d
o
so
m
et
hi
ng
, I
ju
st
w
an
t t
o
al
w
ay
s
le
ar
n
m
or
e.
…
th
ey
d
ef
in
ite
ly
w
an
t t
o
w
rit
e
do
w
n
th
e
su
bt
yp
e
an
d
th
e
gr
ad
e
th
at
th
ey
’re
a
t …
I w
as
ju
st
r
ea
ch
in
g
ev
er
yw
he
re
fo
r
in
fo
rm
at
io
n.
I
sp
en
t m
an
y,
m
an
y
ho
ur
s
do
in
g
re
se
ar
ch
.
I t
ry
to
g
et
a
nd
s
ee
p
ap
er
s
w
he
n
I s
ee
s
om
et
hi
ng
in
th
e
in
te
rn
et
o
r
so
m
et
im
es
I
G
oo
gl
e
it
or
th
e
bo
ok
s
an
d
lit
er
at
ur
es
a
nd
s
m
al
l b
oo
ks
L
LS
h
as
s
en
t t
o
m
e.
C
on
ne
ct
io
n
w
ith
o
th
er
s/
de
ve
lo
pi
ng
a
p
hi
lo
so
ph
y
of
li
fe
(2
2,
1
0)
So
ur
ce
s
of
s
up
po
rt
/s
el
f-e
ffi
ca
cy
Th
e
LL
S
ha
d
a
pe
rs
on
c
o
m
e
an
d
te
ll
m
e
ab
ou
t t
he
i
r
so
cie
ty
, y
ou
k
no
w
w
ha
te
ve
r
th
ei
r,
an
d
th
ey
h
av
e
lik
e
w
ha
t k
in
d
of
y
ou
h
av
e
an
d
yo
u’
re
li
ke
B
-c
el
l a
nd
th
ey
g
ive
y
ou
a
p
am
ph
le
t.
I t
hi
nk
th
at
’s
go
od
to
o
be
ca
us
e
yo
u
do
n’
t k
no
w
w
he
re
to
tu
rn
a
nd
th
en
th
ey
h
av
e,
a
nd
th
ey
a
lso
w
ou
ld
h
oo
k
yo
u
up
w
ith
so
m
eo
ne
if
y
ou
w
an
te
d.
w
he
n
I w
as
fi
rs
t
di
ag
no
se
d,
I
fo
un
d
th
e
su
pp
or
t g
ro
up
fo
r
W
al
de
ns
tr
om
’s
on
lin
e
an
d,
t
w
o,
a
w
om
an
w
ho
h
ad
b
ee
n
in
th
is
tr
ia
l b
ef
or
e
m
e
an
d
w
ho
w
as
v
er
y,
ve
ry
k
no
w
le
dg
ea
bl
e
an
d
w
ho
li
ve
d
no
t f
ar
fr
om
m
e
an
d
I f
ol
lo
w
ed
in
h
er
fo
ot
st
ep
s
af
te
r
re
ad
in
g
a
lo
t a
bo
ut
th
e
dr
ug
s
th
at
w
er
e
in
th
e
tr
ia
l.
If
yo
u
ta
ke
th
e
tim
e
to
e
ith
er
c
om
m
un
ica
te
w
ith
y
ou
r
on
co
lo
gi
st
, w
ith
th
e
Le
uk
em
ia
a
nd
L
ym
ph
om
a
So
cie
ty
w
ith
o
th
er
a
re
as
, y
ou
’ll
fin
d
th
at
y
ou
’
re
n
ot
a
lo
ne
…
I
w
as
b
le
ss
ed
b
ec
au
se
I
fo
un
d
th
e
Le
uk
em
ia
a
nd
L
ym
ph
om
a
So
cie
ty
. L
eu
ke
m
ia
a
nd
L
ym
ph
om
a
So
cie
ty
w
ith
o
th
er
a
re
as
, y
ou
’ll
fin
d
th
at
y
ou
’re
n
ot
a
lo
ne
…
I
w
as
b
le
ss
ed
b
ec
au
se
I
fo
un
d
th
e
Le
uk
em
ia
a
nd
L
ym
ph
om
a
So
cie
ty
. T
he
Le
uk
em
ia
a
nd
L
ym
ph
om
a
So
cie
ty
h
as
a
n
on
lin
e
ch
at
a
nd
I
ac
tu
al
ly
te
xt
w
ith
o
ne
o
th
er
p
er
so
n
ba
ck
an
d
fo
rt
h
be
ca
us
e
it’
s
lik
e
an
o
nl
in
e
ch
at
tw
ice
a
w
ee
k.
I v
ol
un
te
er
ed
a
nd
I
ev
en
h
ad
a
n
on
lin
e
su
pp
or
t g
ro
up
s
pe
cif
ica
lly
fo
r
ag
gr
es
siv
e
lym
ph
om
as
b
ec
au
se
th
er
e
w
as
n’
t a
w
ho
le
lo
t o
f r
es
ou
rc
es
a
va
ila
bl
e
fo
r
m
ys
el
f.
T
ab
le
1
. (
C
on
tin
ue
d)
(C
on
tin
ue
d)
Howson et al. 437
M
ai
n
T
he
m
es
(
N
um
be
r
of
c
od
in
g
re
fe
re
nc
es
+
it
em
s
co
de
d)
D
ef
in
iti
on
s
Ex
em
pl
ar
q
uo
te
Bu
ild
in
g
re
la
tio
ns
hi
ps
w
ith
on
co
lo
gi
st
s
(1
9,
1
0)
M
ak
in
g
su
re
t
he
re
is
a
fi
t
be
tw
ee
n
pa
tie
nt
a
nd
p
hy
si
ci
an
–
ge
tt
in
g
a
se
co
nd
o
pi
ni
on
if
ne
ce
ss
ar
y
It’
s
a
go
od
th
in
g
to
h
av
e
a
gr
ea
t l
ev
el
o
f c
om
fo
rt
w
ith
y
ou
r
do
ct
or
a
nd
tr
us
t i
n
w
ha
t t
he
y’r
e
do
in
g.
I w
ou
ld
e
nc
ou
ra
ge
p
eo
pl
e
to
ta
lk
to
o
th
er
s
to
k
no
w
w
he
re
o
th
er
s
ha
ve
h
ad
p
os
iti
ve
e
xp
er
ie
nc
es
w
ith
do
ct
or
s
or
fa
cil
iti
es
…
y
ou
p
re
tty
m
uc
h
pu
t y
ou
r
lif
e
in
th
ei
r
ha
nd
s.
I w
en
t f
or
a
s
ec
on
d
op
in
io
n
an
d
th
en
I
le
ft
hi
m
fo
r
so
m
eb
od
y
el
se
fo
r
m
y
tr
ea
tm
en
t.
ho
pe
fu
lly
, y
ou
r
do
ct
or
is
a
g
oo
d
pe
rs
on
. I
g
ue
ss
th
at
’s
al
l y
ou
c
an
h
op
e
fo
r
an
d
pe
rh
ap
s
m
ay
be
a
c
ou
pl
e
do
ct
or
s
th
at
a
re
c
om
pl
et
el
y
de
ta
ch
ed
o
r
so
m
ew
ha
t,
no
t a
d
oc
to
r
in
th
e
sa
m
e
ho
sp
ita
l i
s
w
ha
t I
’m
sa
yin
g.
S
o
yo
u
ca
n
ge
t m
ay
be
a
c
om
pl
et
el
y
un
bi
as
ed
s
ec
on
d
op
in
io
n.
I w
as
fo
rt
un
at
e
to
a
t l
ea
st
h
av
e
do
ct
or
s
th
at
li
st
en
ed
to
m
e,
b
ut
th
er
e
w
er
e
tim
es
w
he
re
I
ha
d
to
s
or
t
of
p
us
h
th
em
fo
r
be
tte
r
un
de
rs
ta
nd
in
g
or
s
lo
w
th
em
d
ow
n
w
he
n
th
ey
’re
li
ke
w
el
l w
e
go
t t
o
do
th
is
an
d
al
rig
ht
w
e’
ll
ge
t s
ta
rt
ed
a
nd
I’
m
li
ke
, w
ho
a,
s
lo
w
d
ow
n.
Th
at
if
y
ou
a
re
d
ia
gn
os
ed
w
ith
a
B
-c
el
l l
ym
ph
om
a,
y
ou
n
ee
d
to
b
e
an
d
un
de
r
th
e
ca
re
o
f a
he
m
at
ol
og
ist
o
nc
ol
og
ist
w
ho
h
as
n
um
er
ou
s
ot
he
r
pa
tie
nt
s
an
d
ex
pe
rie
nc
e
w
ith
y
ou
r
pa
rt
icu
la
r
di
se
as
e
…
th
ey
a
re
g
oi
ng
to
tr
ea
t y
ou
w
ith
m
or
e
kn
ow
le
dg
e,
m
or
e
ex
pe
rie
nc
e.
Yo
u
w
ill
ha
ve
to
c
ho
os
e
th
e
rig
ht
d
oc
to
r
an
d
th
en
y
ou
’ll
ha
ve
to
h
av
e
th
e
qu
es
tio
ns
,
w
hi
ch
a
re
v
er
y
im
po
rt
an
t a
nd
w
hi
ch
w
as
d
isc
us
se
d
in
th
es
e
vid
eo
q
ue
st
io
ns
a
re
v
er
y
im
po
rt
an
t,
w
hi
ch
I
us
ed
to
d
o.
I w
ill
te
ll
th
e
sa
m
e
th
in
g
to
o
th
er
p
eo
pl
e.
Y
ou
jo
t d
ow
n
an
d
do
n’
t,
yo
u
do
n’
t h
av
e
to
h
es
ita
te
to
a
sk
th
es
e
qu
es
tio
ns
a
bo
ut
y
ou
r,
I w
ill
sa
y
ab
ou
t y
ou
r
w
or
rie
s,
ab
ou
t y
ou
r
co
nc
er
ns
. Y
ea
h,
g
o
ah
ea
d
an
d
fe
el
fr
ee
. I
f y
ou
a
re
n
ot
s
at
isf
ie
d,
w
hi
ch
I
di
d,
g
o
an
d
se
e
an
ot
he
r
on
e
fo
r
a
se
co
nd
o
pi
ni
on
.
Th
e
fir
st
o
nc
ol
og
ist
th
at
I
w
en
t t
o
I d
id
n
ot
c
ar
e
fo
r
he
r
m
ed
ica
l.
I’m
a
d
oc
to
r.
I d
id
n
ot
c
ar
e
fo
r
he
r
m
ed
ica
l a
tti
tu
de
o
r
ap
pr
oa
ch
es
, b
ut
s
he
ju
st
to
ld
m
e
th
at
I
w
ou
ld
b
e
de
ad
in
5
to
1
0
ye
ar
s
an
d,
fo
rt
un
at
el
y,
I q
ui
ck
ly
le
ft
he
r
as
a
n
on
co
lo
gi
st
a
nd
I
ha
d
st
ay
ed
w
ith
a
no
th
er
o
nc
ol
og
ist
w
ho
fo
rt
un
at
el
y
re
tir
ed
th
is
Fe
br
ua
ry
.
T
ab
le
1
. (
C
on
tin
ue
d)
438 Health Education Journal 77(4)
Participants contextualised the self-care strategies they described in terms of being aware of
one’s body and checking for bodily changes (‘you have to listen to your body and your body is
going to tell you that things are a little bit different now’), caring for one’s immune system by mini-
mising interaction with people (treatment is associated with immune system compromise), and
making adjustments to activities in the presence of fatigue or other bodily signs and symptoms.
Rest was identified as important to help manage the treatment process (i.e. infusions) and treat-
ment-related side effects, as was the notion of being kind to oneself.
Learning the hard way/everyone is different. Participants’ experience had taught them that the approach
to B-cell treatment could change over time. They emphasised the importance of having information
available to them to support their active involvement in self-care as a life-time task, and to prepare
them for what many viewed (in particular, those with diffuse B-cell NHL) as a long, but potentially
manageable journey. Despite the need for such information, as summarised in Table 1, learning the
hard way represented a principal learning modality for knowledge acquisition about B-cell NHL
self-care. Participants described having little awareness of, or access to, information to support self-
care, for instance, in relation to treatment side-effect management. Participants also recognised that
the experience of B-cell NHL diagnosis and treatment is unique for everyone – that ‘everyone is
different’ and no one is ‘a textbook patient’ – especially since there are so many sub-types.
Being prepared for self-care. Participants’ descriptions of self-care practices were accompanied by a
recurring belief in the importance of being prepared, that is, being proactive in learning about their
disease and updating their information about potential treatment and management options via four
key strategies: (1) asking questions, (2) building relationships with oncologists, (3) developing/
maintaining a philosophy of life and (4) connecting with others.
1. Asking questions
When asked to describe to another person about what to expect at diagnosis (Figure 1, Q4), partici-
pants emphasised the importance of asking questions about which tests they ought to have at diag-
nosis and emphasised the importance of being engaged with their diagnosis by doing their own
research:
You need to do your own research is what I would tell everybody and I would also say, whatever their
diagnosed with, whether it’s lymphoma or anything else, question authority. Question the doctor. If
something doesn’t feel right or sound right, you need to look it up and tell them. (Patient 12)
Patient involvement in discussing options for treatment was a key message presented in the
education activity, which provided examples of questions to ask healthcare providers. Participants
saw these questions as an especially valuable resource to support being prepared. Even though
participants were motivated to engage in self-care behaviours, and in many cases already well-
equipped to do so, they felt that having specific examples of questions to ask was an additional tool
that enabled them to be more in control of their disease experience and more involved in
decision-making:
I don’t want you just telling me this is the treatment because if I tell you I have these issues of medical
history and things like that will that alter the course? I want to make sure that my doctor is open minded.
I want to make sure that my doctor has, is willing to tailor and customise a plan and not have this one size
fits all. (Patient 1)
Howson et al. 439
Participants also emphasised the importance of asking healthcare providers about the range of
options available across the disease trajectory, and patients who volunteered as peer supporters
with LLS also wanted to be equipped to encourage other patients to ask questions.
2. Building relationships with oncologists
Having a good oncologist, getting a second opinion, or switching to another oncologist represented
further dimensions of being prepared. Half of the participants shared stories about a convoluted
diagnostic process involving what they viewed as poor clinical judgement or skills, poorly man-
aged and painful bone marrow biopsies, not getting a straight answer or poor bedside manner.
These were commonly cited triggers for finding an alternative oncologist and building robust rela-
tionships with physicians:
I asked my oncologist if I was going to die straight out and he said no. So just ask. Whatever fears you
have, just ask him and if he doesn’t really respond, then you get a different oncologist. (Patient 11)
If you are not satisfied, which I did, go and see another one for a second opinion. In America, there is
nothing wrong in that. It is your right, I think. That’s what I will say. If you get a right doctor and right
diagnosis, you are on the right track. (Patient 5)
3. Developing/maintaining a philosophy of life
Participants emphasised the importance of building a support system to provide practical support
(e.g. grocery shopping and general household chores) and ‘to encourage you to do the things that
you know you should do’. Many of the participants in this sample were single, and described them-
selves as ‘doing this alone’. Online resources and local support groups helped this group cope with
their disease and the side effects of treatment. Faith, spirituality and having a positive attitude also
played a role as part of ‘being prepared’:
I’d say my faith is very important to me, and so that’s a big thing that got me through is the people that I
knew were praying for me and I prayed for myself. (Patient 9)
I think you need to live your life as much as you can. (Patient 6)
4. Connecting with others
Active engagement as patient citizens was also connected to being prepared. Such engagement
included volunteering for the LLS, acting as peer support providers, offering advocacy, and partici-
pating in fund raising. Most participants also commented during their interview that they were
eager to participate in the education activity, and saw it as an opportunity to not only refresh their
own information, but also as a way to remain connected to the LLS and/or B-cell NHL
community.
The patient vignettes included in the education content also offered an opportunity for connec-
tion. Participants viewed the vignettes as providing a window into the real-life, lived experience of
B-cell NHL. In contrast to ‘textbook science mumbo jumbo’, (Patient 7) vignettes provided a
personalised, authentic opportunity for participants to learn ‘from people that actually are going
through it’ (Patient 6), ‘how they experienced it, what they decided to do and where they are today’
(Patient 7):
440 Health Education Journal 77(4)
It was helpful to hear what other peoples’ experiences were. I think that’s probably the most valuable thing
that I think that I was seeking out. I mean, it’s one thing [if] you can find a lot of research on or, you know,
finding different medical treatments and pros and cons and all that, but it’s a little harder to find actual
feedback from patients’ experiences. It would be good for some peoples’ psychological aspect to see
there’s a lot of success stories out there. (Patient 7)
Discussion
Qualitative insights on self-care and PSE in B-cell NHL
This study explored education impact on knowledge about and perspectives on self-care and self-
efficacy in the context of a B-cell NHL diagnosis. Following participants’ participation in an online
education activity, participants demonstrated sustained knowledge about practical self-care behav-
iours, and were able to describe key messages presented in the programme. They emphasised the
importance of intentionally caring for themselves via functional behaviours (e.g. practicing good
nutrition, being physically active within their personal limits, connecting with others in ways that
were consistent with not only education messages) that also correspond broadly to categories of
self-care previously described in the literature on chronic disease (Barofsky, 1978; Bury et al.,
2005). Participants emphasised the value of learning about which questions to ask, and reported
they would use them going forward when they next met with their healthcare providers. These
findings suggest that the education achieved its aim to support self-efficacy by reinforcing existing
PSE through social persuasion. This finding is consistent with social cognitive theory (e.g. Bandura,
1997), on which models of health behaviour change are based. These models assert that self-beliefs
derived from interactions between personal, environmental or situational and behavioural determi-
nants influence learning, action and behaviour change.
The health behaviour literature describes PSE as an important precursor to action that is sus-
tained by an individual’s beliefs in their ability to act in ways that will accomplish particular out-
comes (Bandura, 1986, 1995; Prochaska and DiClemente, 1982). Although PSE beliefs reflect what
people believe they are able to do in a particular situation rather than actual performance, such
beliefs are, nonetheless, seen to influence the performance of particular behaviours, such as engag-
ing in self-care in the context of chronic disease or cancer. In turn, PSE beliefs are influenced by
information from several sources, including one’s own experience and social persuasion. However,
there is little empirical description of the beliefs that underlie PSE (Burke et al., 2009). Instead,
much of the health education/behaviour literature on self-efficacy utilises quantitative scores (e.g.
PSE for Fatigue Self-Management Scale, Hoffman et al., 2009) to measure self-efficacy as a cogni-
tive construct. These measures presume the significance of rational action in health behaviours and
practices but overlook the sources, salience, and specificity of PSE beliefs, as well as, more broadly,
the social contexts that influence beliefs, and in which beliefs are enacted (Burke et al., 2009).
When we explored interview data inductively, we discerned four themes related to the practice
of self-care, including normalisation of self-care, learning the hard way, everyone is different and
being prepared. These themes provide context to the experience of self-efficacy in the context of
B-cell self-care, and suggest that in order to enact self-care, participants believed that they needed
to be prepared, and pointed to a number of strategies that enabled them to be prepared. These find-
ings point to self-efficacy as a fluid social concept and underscore the need for wider exploration
of the meanings that people hold for self-efficacy in the context of self-care. In a similar vein,
recent systematic reviews suggest that the meaning and enactment of self-efficacy varies across
cultural context and ethnicity (Stewart et al., 2009) and represents a resource for both individuals
and communities (Boehmer et al., 2016).
Howson et al. 441
Practice implications
The themes identified in this study have potential implications for self-efficacy education. First,
participants viewed self-care as a normalised aspect of living with B-cell NHL. As cancer evolves
into a chronic disease, educators can cultivate this normalisation through interventions that enable
patients to view self-care as a part of the routine of living long-term with cancer, and help them
make tailored adjustments and modifications to daily activities in response to changes in disease-
and treatment-specific signs and symptoms.
Second, knowledge acquisition about B-cell NHL was hard won for participants in this study;
however, learning the hard way has the potential to stymie self-efficacy. Expanding the availability
and accessibility of information for patients with B-cell NHL is a necessary foundation for building
self-efficacy in relation to self-care in this context. Third, the experience of living with B-cell NHL
differs for people by subtype and other factors. The perception that everyone is different poses
potential barriers to self-efficacy if patients do not see themselves reflected in educational materi-
als. Educational interventions can encourage PSE and authenticate self-care strategies by reflecting
variations in the lived experience of others by using, for example, vignettes that provide a window,
or a ‘vicarious experience’, into the experience of B-cell NHL.
Finally, being prepared may represent an underlying belief that supports PSE in the B-cell NHL
context. Participants linked being prepared to specific strategies such as asking questions of health-
care providers, building relationships with healthcare providers, enacting a philosophy of life and
connecting with other B-cell patients. This linkage between belief and action points to self-efficacy
as a dynamic process, as well as a cognitive construct. As such, the meanings that people hold for
self-efficacy in other self-care contexts warrant empirical specification as a foundation for devel-
oping meaningful, targeted patient education.
Limitations
Participants who chose to participate in this educational intervention self-selected to seek further
information about B-cell NHL, and may be atypical of the general population with this disease. We
contend, however, that the strong engagement of participants with their disease allowed us to
explore the meaning of self-efficacy from their perspectives, and to flesh out the factors associated
with influencing and reinforcing PSE. The sample size is small; however, small sample size is
conventional in qualitative research, when the purpose is to yield meaningful insights or generate
hypotheses, versus generalisable results.
Conclusion
Patient education programmes are becoming especially germane in the context of changing epide-
miology and patient demographics (Beaser et al., 2017; Rothrock et al., 2006). Such education is
important to enable patients with chronic disease and illness, including some cancers, to participate
in self-care. As populations in both Europe and the USA age, the prevalence of chronic conditions
– including many cancers – will also increase, and both clinician shortages and rising healthcare
costs add to the necessity of patient involvement in disease self-care (Frenk et al., 2010). Research
suggests that patients with the capacity to cope with disease, treatment and treatment-related side
effects are better able to adjust to their diagnosis and experience a greater quality of life (Zachariae
et al., 2003). Building self-efficacy is key to developing this capacity to cope with self-care; how-
ever, the beliefs underpinning self-efficacy remain under-investigated. The themes generated by
this qualitative study provide insights on which educators can draw to strengthen self-efficacy
442 Health Education Journal 77(4)
education interventions for patients with B-cell NHL and other types of cancer. In particular, edu-
cators can consider soliciting information from patients about the experience and meanings of both
self-care and their self-efficacy beliefs.
Acknowledgements
We are grateful to the people who participated in this education programme and who agreed to be interviewed
for this study.
Funding
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publica-
tion of this article: This study was funded by an independent educational grant from Pharmacyclics LLC, an
Abbvie Company, Janssen Biotech, Inc., (administered by Janssen Scientific Affairs, LLC), and Genentech.
Supplementary Material
Supplementary material for this article is available online.
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875Dorleijn DMJ, et al. Ann Rheum Dis 2018;77:875–882. doi:10.1136/annrheumdis-2017-212628
Clinical and epidemiological research
ExtEndEd rEport
Intramuscular glucocorticoid injection versus placebo
injection in hip osteoarthritis: a 12-week blinded
randomised controlled trial
desirée M J dorleijn,1 pim A J Luijsterburg,1 Max reijman,2 Margreet Kloppenburg,3
Jan A n Verhaar,2 patrick J E Bindels,1 pieter Koen Bos,2 Sita M A Bierma-Zeinstra1,2
AbstrACt
Objectives Guidelines recommend intra-articular
glucocorticoid injection in patients with painful hip
osteoarthritis. However, intra-articular hip injection
is an invasive procedure. the efficacy of systemic
glucocorticoid treatment for pain reduction in
hip osteoarthritis is unknown. this randomised,
double-blind, trial assessed effectiveness in hip pain
reduction of an intramuscular glucocorticoid injection
compared with a placebo injection in patients with hip
osteoarthritis.
Methods patients with painful hip osteoarthritis were
randomised to either 40 mg triamcinolone acetate or
placebo with an intramuscular injection into the gluteus
muscle. the primary outcomes were severity of hip pain
at rest, during walking (0–10) and WoMAC pain at
2-week postinjection. We used linear mixed models for
repeated measurements at 2, 4, 6 and 12 weeks for the
intention-to-treat data analysis.
results of the 107 patients randomised, 106 could
be analysed (52 in the glucocorticoid group, 54 in the
placebo group
).
At 2-week follow-up, compared with
placebo injection, the intramuscular glucocorticoid
injection showed a significant and clinically relevant
difference in hip pain reduction at rest (difference −1.3,
95% CI −2.3 to −0.3). this effect persisted for the entire
12-week follow-up. For hip pain during walking, the
effect was present at 4-week, 6-week and 12-week
follow-ups, and for WoMAC pain the effect was present
at 6-week and 12-week follow-up.
Conclusions An intramuscular glucocorticoid injection
showed effectiveness in patients with hip osteoarthritis
on one of the three primary outcomes at 2-week
postinjection. All primary outcomes showed effectiveness
from 4 to 6 weeks, up to a 12-week follow-up.
trial registration number ntr2966.
IntrOduCtIOn
Several international guidelines recommend
intra-articular (IA) glucocorticoid injections for
patients with hip osteoarthritis (OA) experiencing
moderate to severe pain and not responding to oral
analgesics.1–3 A systematic review on the efficacy of
intra-articular steroids in moderate/severe hip OA
included five randomised controlled trials (RCT)
and the assessed quality of the studies was high.4
The treatment effect was large at 1 week post-in-
jection, but declined afterwards. At 8 weeks, there
were two trials that reported a reduction in pain
with a moderate effect size.4
However, injection into the hip joint is chal-
lenging because the joint cannot be palpated and
is adjacent to important neurovascular structures.
An IA hip injection is best performed under fluoro-
scopic or ultrasound guidance.
A serious side effect of an IA injection is a septic
arthritis. The incidence of this side effect is very low,
and scarce in the available literature. A systematic
review and meta-analysis of IA injection in knee OA
comparing effectiveness of pharmacological inter-
ventions included 29 studies (3152 patients, 9500
IA glucocorticoid injections) and reported only 1
septic arthritis (in the IA placebo group).5
A systemic effect of glucocorticoids on joint pain
has been indicated in patients with subacromial
impingement shoulder pain. A double-blinded RCT
showed no important differences in effectiveness
on pain of ultrasound-guided subacromial gluco-
corticoid injection compared with gluteal injec-
tion.6 A systemic effect of glucocorticoids was also
suggested in an RCT reporting the effect of local
glucocorticoid injection for greater trochanteric
pain syndrome: patients with concurrent hip OA or
chronic low back pain had an equal or even more
pronounced decrease in pain.7 8
If an intramuscular (IM) glucocorticoid injection
is shown to have a clinically relevant effect on pain,
this would offer a less complex alternative treatment
for episodes of increased pain in hip OA. Therefore,
this study assessed the efficacy of an IM glucocorti-
coid injection compared with an IM placebo injec-
tion on hip pain severity in patients with hip OA
who were not responding to oral analgesics.
MethOds
trial design
This was a multicentre, double-blinded, randomised
controlled superiority trial with two parallel groups
and a follow-up period of 12 weeks: details of
the study protocol were published earlier.9 10 The
Medical Ethics Committee of the Erasmus Univer-
sity Medical Centre (EMC; Rotterdam) approved
the study protocol (MEC2011-115) and all included
patients provided written informed consent.
Patients
Patients with hip OA were invited to participate in
the trial by general practitioners and orthopaedic
surgeons located in the south-west of the Nether-
lands. Patients (aged >40 years) were eligible for
inclusion if they met the American College for
to cite: dorleijn dMJ,
Luijsterburg pAJ, reijman M,
et al. Ann Rheum Dis
2018;77:875–882.
handling editor Josef S
Smolen
► Additional material is
published online only. to view
please visit the journal online
(http:// dx. doi. org/ 10. 1136/
annrheumdis- 2017- 212628).
1department of General
practice, Erasmus MC University
Medical Center rotterdam,
rotterdam, the netherlands
2department of orthopaedics,
Erasmus MC University Medical
Center rotterdam, rotterdam,
the netherlands
3department of rheumatology,
Leiden University Medical
Center, rotterdam, the
netherlands
Correspondence to
desirée M J dorleijn,
department of General practice,
Erasmus MC University Medical
Center rotterdam, rotterdam
3000 CA, the netherlands;
d. dorleijn@ erasmusmc. nl
received 1 november 2017
revised 17 February 2018
Accepted 18 February 2018
published online First
7 March 2018
http://www.eular.org/
http://ard.bmj.com/
www.trialregister.nl
http://crossmark.crossref.org/dialog/?doi=10.1136/annrheumdis-2017-212628&domain=pdf&date_stamp=2018-05-08
876 Dorleijn DMJ, et al. Ann Rheum Dis 2018;77:875–882. doi:10.1136/annrheumdis-2017-212628
Clinical and epidemiological research
Rheumatology (ACR) clinical criteria for hip OA during clinical
screening and radiological evidence of hip OA was present (Kell-
gren & Lawrence ‘score’ (KL) ≥2).11 12 Patients were included if
they had symptomatic disease for ≥6 months, and had moderate
to severe hip pain score ≥3 (scale 0–10; 0=no pain) despite the
use of oral analgesics at time of inclusion.
Radiological hip OA was scored on an anterior–posterior
pelvic radiograph of (at most) 6-month old. The radiological
grade of hip OA was scored by two researchers (DD, PKB)
independently and the interobserver reliability was κ=0.7 for
KL <2 vs KL ≥2. In case of disagreement, a consensus was
formed during a consensus meeting. If a patient had bilateral hip
OA, the more painful hip was selected as the study hip.
Patients were excluded if they had diabetes mellitus, were
using oral glucocorticoids, had local/systemic infection, had
presence of inflammatory rheumatic diseases (eg, rheumatoid
arthritis, psoriatic arthritis and spondylarthropathies), coagulop-
athy, used coumarins, had a gastric ulcer, allergy to glucocorti-
coids, radiological signs of osteonecrosis, had an IA injection in
the hip in the previous 6 months, were on the waiting list for
total hip replacement (THR) surgery or were unable to complete
questionnaires in Dutch.
Interventions
Patients received either 40 mg triamcinolone acetate (1 mL)
or 1 mL normal saline (placebo) with an IM injection. At the
research centre, the trial nurse administered the allocated injec-
tion in the upper lateral quadrant of the gluteal musculature on
the ipsilateral side of the study hip.
randomisation
An independent pharmacy assistant allocated each included
patient based on a computerised randomisation list using random
blocks of 2 and 4 to either placebo (saline) injection or triamcin-
olone acetate 40 mg injection. Randomisation was stratified for
setting (general practice and orthopaedic outpatient clinic). After
randomisation, the vials for the injections were prepared, packed
and sealed in an identical way for both groups by the pharmacy
of the EMC. The randomisation list was available only to the
pharmacy assistant.
blinding
In this trial, the outcome assessors, patients, treating physicians,
researchers (including the statistical analyses) and research assis-
tants involved in data collection were blinded to the content of
the injections. Since normal saline is transparent and triamcin-
olone acetate is a white solution, the independent nurse who
prepared and injected the injection was non-blinded. To assure
blinding of the others, the independent trial nurse prepared and
administered the injection out of sight of the patient, assessors,
treating physicians and the researchers. This trial nurse was not
involved with follow-up measurements. After preparation and
before injection, the syringe was covered with an opaque foil to
assure blinding of the patient.
Outcom
es
The primary outcomes were severity of hip pain at 2-week post-
injection measured on an 11-point numerical rating scale (NRS:
0–10, 0=no pain) at rest and during walking, and measured
with the Western Ontario and McMaster University Osteoar-
thritis Index pain subscale (WOMAC pain: 0–100, 0=no symp-
toms).13 1
4
Secondary outcomes were the primary outcomes at 4-week,
6-week and 12-week follow-ups. Additional secondary outcome
measures were WOMAC function and stiffness, WOMAC total
score, Hip disability and Osteoarthritis Outcome Score for pain
(HOOS pain), quality of life (EQ-5D), Intermittent and Constant
Osteoarthritis Pain (ICOAP) and patients’ perceived recovery
assessed on a 7-point Likert scale.15–17 At all time points, the
WOMAC and ICOAP scales are presented as normalised scores
(0–100, 0=no symptoms). The HOOS subscale is presented as
normalised score (0–100, 100=no symptoms). Also recorded
was patients’ medical consumption, including analgesic use and
adverse reactions at all time points. Patients were allowed to use
escape pain medication as needed.
Another secondary outcome was the percentage of responders
as defined by the OMERACT-OARSI criteria (improvement in at
least two of the three following domains: ≥20% improvement
in WOMAC pain, ≥20% improvement in WOMAC function
and markedly improved on patients’ global assessment).16 For
patients’ global assessment the 7-point Likert scale for patients’
perceived recovery was dichotomised in ‘improved’ (scores:
completely recovered, almost completely recovered and slightly
recovered) and ‘not improved’ (scores: no change, slightly
worse, significantly worsened and worse than ever).
At baseline and at a 12-week follow-up, patients visited the
research centre to undergo a physical examination of hips, spine
and knees. At baseline, blood samples were collected to measure
the erythrocyte sedimentation rate and C reactive protein to gain
insight in the inflammatory processes.14
sample siz
e
Power calculations were based on a study with similar inclusion
criteria.18 A 10-point difference (SD 20) on hip pain at rest and
during walking (visual analogue scale: 0–100) was assumed to
be the minimal clinically important difference between both
groups.19 The accompanying effect size of 0.5 is from the clinical
standpoint a moderate effect and in general considered clinically
relevant.20 For our study, this implies one point on the NRS pain
scale. With a power of 80% and an alpha of 5%, 64 patients
per group were required (including 5% loss to follow-up=67
patients per group). The same sample size was needed when an
8-point difference (SD 16) on the standardised WOMAC total
score and pain subscale score (0–100) was assumed as a clinically
relevant difference between the groups.
statistical analysis
The intention-to-treat principle was used. Descriptive statistics
were used to describe patients’ characteristics at baseline, items
of physical examination and the severity of radiologic hip OA.
Linear mixed models with repeated measures were used for
continuous outcomes. When patients underwent a THR, data of
these patients were included up to the date of surgery. To model
the covariance of repeated measures by patients, the option for
data structure in the analyses was set on ‘unstructured’, because
this yielded the lowest Akaike’s information criterion. Fixed
effects were time and time by treatment. Analyses were adjusted
for baseline variables and for the baseline value of the outcome
of interest.9 Therefore, at a 2-week follow-up presented are the
outcomes at 2 weeks, corrected for baseline scores. At 4 weeks,
presented are the results at a 4-week follow-up time point,
corrected for baseline and 2 weeks scores and so on.
Generalised estimating equations (GEE) analyses with repeated
measures were performed for the dichotomous outcomes
perceived improvement, and the OMERACT-OARSI responder.
877Dorleijn DMJ, et al. Ann Rheum Dis 2018;77:875–882. doi:10.1136/annrheumdis-2017-212628
Clinical and epidemiological research
Before GEE analyses, multiple imputations were performed for
missing values, creating 100 imputed datasets.
The Pearson χ2 test was used to analyse differences between
groups concerning medical consumption, analgesic use and
adverse events. An explorative, predefined, subgroup analysis
was performed assessing the interaction effects between injec-
tions and setting on the primary outcomes.
9
All analyses were performed using SPSS V.24.
results
Patient flow
A total of 422 invited patients contacted the research centre and
were screened for eligibility; of these, 92 refused to participate
and 223 did not meet the inclusion criteria (figure 1).
Finally, 107 patients provided informed consent: 53 were
randomised to the glucocorticoid injection and 54 to the placebo
injection. One patient in the glucocorticoid group withdrew his
consent just before the appointment for baseline physical exam-
ination and subsequent injection, because his pain had resolved
spontaneously. Because this patient did not receive the allocated
treatment and was not willing to send us the completed base-
line questionnaire or any follow-up questionnaires, he was not
included in the analyses.
recruitment
Recruitment of patients took place between September 2011
and October 2014 and follow-up measurements were done until
January 2015. Of the 107 included patients, general practi-
tioners referred 81 patients.
lost to follow-u
p
At a 6-week follow-up, one patient in the glucocorticoid group
reported being scheduled for a THR; in the placebo group two
patients (at 4-week and 6-week follow-up, respectively) reported
being scheduled for a THR. One patient in the placebo group
was not willing to participate after 6 weeks due to logistical
problems.
Patient population
Of all patients, 52 received the allocated glucocorticoid injec-
tion and 54 the allocated placebo injection, and were included
in the analyses. Baseline characteristics of both patient groups
are presented in table 1. Of the 106 patients, 73 (68%) were
women; the mean age was 64 (SD 11) years, and the duration of
hip OA symptoms was ≥1 year for 74 (70%) patients.
Figure 1 Flow diagram of the study participants. NRS, Numerical Rating Scale (0–10; 0=no pain); FU, follow -up; IA, intra-articular; KL, Kellgren &
Lawrence ‘score’ for hip osteoarthritis; THR, total hip replacement; wks, weeks.
878 Dorleijn DMJ, et al. Ann Rheum Dis 2018;77:875–882. doi:10.1136/annrheumdis-2017-212628
Clinical and epidemiological research
The KL score of hip OA at baseline, ethnicity, morning hip
stiffness and patients’ expected effect of the injection changed
the estimates for the primary outcome ≥10%. We adjusted for
these baseline variables in the statistical analyses.
Primary outcomes
At a 2-week follow-up, compared with the placebo injection,
the glucocorticoid injection showed a significant association
with hip pain reduction at rest (between group difference −1.3,
95% CI −2.3 to −0.3) (table 2 and figure 2). Also, at a 2-week
follow-up, there were no significant associations between gluco-
corticoid injection and hip pain during walking (difference
−0.9, 95% CI −1.9 to 0.1) and WOMAC pain (difference −6.1,
95% CI −13.4 to 1.2). The correlation between the primary
endpoints ranged from r 0.64 to r 0.84. The results of the unad-
justed linear mixed model analysis were similar (online supple-
mentary table S1).
secondary outcomes
At 4-week, 6-week and 12-week follow-ups, the glucocorticoid
injection was associated with a significant hip pain reduction
at rest and during walking (table 2 and figure 2). Moreover,
at almost all follow-up measurements, the estimates showed
significant differences in favour of the glucocorticoid injec-
tion on WOMAC pain, function, stiffness and total; HOOS
pain; and ICOAP total, intermittent and constant. No signifi-
cant differences between groups were found for quality of life
(table 2). At a 2-week follow-up, perceived improvement and
table 1 Patients’ characteristics at baseline
Characteristic
Glucocorticoid
(n=52)
Placebo
(n=54)
Age, years, mean±SD 66±11 63±10
Body mass index, kg/m2, mean±SD 27±3.7 28±6.4
Women, n(%) 40 (77) 33 (61)
Duration of symptoms, n(%) ≥1 year 40 (77) 34 (63)
Referral to study by, n(%) General practitioner 39 (75) 41 (76)
Kellgren & Lawrence score hip OA, n(%) KL 2 42 (81) 38 (70)
Ethnicity Dutch, n(%) 51 (98) 47 (87)
Employment, n(%) 17 (33) 23 (43)
Comorbidities
Osteoarthritis of knee(s), n(%) 20 (39) 15 (28)
Osteoarthritis of hand(s), n(%) 12 (23) 14 (26)
Low back pain, n(%) 33 (64) 30 (56)
Signs and symptoms
Stiffness of the hip, n(%) Morning stiffness 40 (77) 35 (65)
Severity of hip pain last week NRS 0–10, mean±SD Pain at rest 4.3±2.4 4.2±2.5
Pain at walking 5.4±2.1 5.1±2.3
WOMAC 0–100, mean±SD Total score 46±19 47±18
Pain 43±17 43±17
Function 47±20 48±19
Stiffness 52±21 48±24
HOOS 0–100, mean±SD Pain 52±17 52±16
ICOAP 0–100, mean±SD Total score 38±18 39±17
Intermittent pain 41±21 41±17
Continuous pain 34±21 36±19
EQ-5D score, mean±SD 0.66±0.23 0.68±0.26
Treatment
Frequent pain medication use*, n(%) Acetaminophen 25 (48) 26 (48)
NSAID 14 (27) 14 (26)
Opiates 8 (15) 6 (11)
Visited healthcare giver for hip OA in the previous
3 months, n(%)
General practitioner
n of visits (median, IQR)
24 (46)
1 (1)
22 (41)
1 (0)
Physiotherapist
n of visits (median, IQR)
14 (27)
6 (11)
22 (41)
6 (5)
Medical specialist
n of visits (median, IQR)
16 (31)
1 (0)
18 (33)
1 (0.3)
Patient’s expected effect of injection, n(%) Much or very much 36 (69) 29 (54)
Laboratory outcomes
CRP, median (IQR) 2 (3.1) 1.5 (3.4)
ESR, median (IQR) 9.5 (13) 10 (12)
*Frequent pain medication use=3–5 times/week or daily use in the past 3 weeks.
ADL, function in daily living; CRP, C reactive protein; EQ-5D, Euroqol; ESR, erythrocyte sedimentation rate; HOOS, Hip Disability and Osteoarthritis Outcome Score (0=extreme
problems); ICOAP, Intermittent and Constant Osteoarthritis Pain (0=no pain); KL, Kellgren & Lawrence grading of radiologic hip OA; NRS, Numeric Rating Scale (0=no pain); NSAID,
non-steroidal anti-inflammatory drug; OA, osteoarthritis; WOMAC, Western Ontario and McMaster University Osteoarthritis Index (0=no pain).
https://dx.doi.org/10.1136/annrheumdis-2017-212628
https://dx.doi.org/10.1136/annrheumdis-2017-212628
879Dorleijn DMJ, et al. Ann Rheum Dis 2018;77:875–882. doi:10.1136/annrheumdis-2017-212628
Clinical and epidemiological research
ta
b
le
2
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4
Q
ua
lit
y
of
li
fe
EQ
-5
D
0.
77
(0
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4)
0.
71
(0
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1)
0.
05
−
0.
02
t
o
0.
13
0.
14
0.
74
(0
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0)
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(0
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4)
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03
−
0.
06
t
o
0.
12
0.
51
0.
78
(0
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7)
0.
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(0
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0)
0.
06
−
0.
01
t
o
0.
14
0.
10
0.
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(0
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8)
0.
69
(0
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6)
0.
08
−
0.
01
t
o
0.
17
0.
09
*P
la
ce
bo
g
ro
up
is
r
ef
er
en
ce
g
ro
up
.
Va
lu
es
in
m
ea
n
(S
D
);
N
RS
p
re
se
nt
ed
a
s
0–
10
s
co
re
; W
O
M
A
C
a
nd
IC
O
A
P
pr
es
en
te
d
as
0
–1
00
s
co
re
; m
od
el
a
dj
us
te
d
fo
r
KL
-s
co
re
a
t
ba
se
lin
e,
e
th
ni
ci
ty
, m
or
ni
ng
s
tif
fn
es
s
an
d
pa
tie
nt
s’
e
xp
ec
te
d
ef
fe
ct
o
f i
nj
ec
tio
n
an
d
fo
r
th
e
ba
se
l
in
e
va
lu
e
of
t
he
o
ut
co
m
e
of
in
te
re
st
;
g
lu
co
co
rt
ic
oi
d
gr
ou
p
n=
52
; p
la
ce
bo
g
ro
up
n=
54
.
Ra
ng
e
m
is
si
ng
v
al
ue
s:
n
=
0
a
t
ba
se
lin
e
an
d
2-
w
ee
k
fo
llo
w
-u
p
to
n
=
4
a
t
12
–
w
ee
k
fo
llo
w
-u
p.
Δ
, b
et
w
ee
n
gr
ou
p
di
ff
er
en
ce
; C
C
S,
g
lu
co
co
rt
ic
oi
d;
E
Q
-5
D,
E
ur
oQ
ol
fi
ve
d
im
en
si
on
s
ca
le
; H
O
O
S,
H
ip
d
is
ab
ili
ty
a
nd
O
st
eo
ar
th
rit
is
O
ut
co
m
e
Sc
or
e
(0
=
ex
tr
e
m
e
pr
ob
le
m
s)
; I
C
O
A
P,
In
te
rm
itt
en
t
an
d
C
on
st
an
t
O
st
eo
ar
th
rit
is
P
ai
n;
N
RS
, N
um
er
ic
al
R
at
in
g
Sc
al
e
(0
=
no
p
ai
n)
; W
O
M
A
C
, W
es
te
rn
O
nt
ar
io
a
nd
M
cM
as
te
r
U
ni
ve
rs
iti
es
In
de
x
(0
=
n
o
pa
in
).
880 Dorleijn DMJ, et al. Ann Rheum Dis 2018;77:875–882. doi:10.1136/annrheumdis-2017-212628
Clinical and epidemiological research
the OMERACT-OARSI responders showed a significant effect in
favour of glucocorticoid injection: RR 1.7 (95% CI 1.1 to 2.7)
and 2.0 (95% CI 1.1 to 3.6), respectively (table 3).
Adverse events and medical consumption
In the glucocorticoid group, 19 patients reported 27 adverse
events. In the placebo group 13 patients reported 18 adverse
events. All adverse events were classified as non-serious (table 4).
Hot flushes, headache and itching were reported most frequently
in the glucocorticoid group. There were no significant differences
in medical consumption between the two groups (online supple-
mentary table S2).
Ancillary analyses
In the explorative subgroup analyses, the results of the interac-
tion of setting on injections showed no significant differences
between the two groups (NRS at rest 1.5, 95% CI −0.6 to 3.7).
dIsCussIOn
We found that an IM glucocorticoid injection showed effec-
tiveness in patients with hip OA on one of the three primary
outcomes at a 2-weeks postinjection and that the effect is prob-
ably clinically relevant. All primary outcomes and almost all
secondary pain and function outcomes showed effectiveness
from 4 to 6 weeks that lasted for the entire 12- weeks follow-up.
The highest effects were seen at 4–12 weeks follow-up instead of
at the expected 2-weeks follow-up.
In this study, three primary endpoints were used. This
increases the risk of a type 1 error. However, with a bonfer-
roni correction for the three primary outcomes (p<0.017) pain
at rest was still significantly associated with pain reduction at
a 2-week follow-up.
It was surprising that hip pain reduction after IM glucocor-
ticoid injection was still present at a similar degree at 12-week
follow-up. Previous studies on IA glucocorticoid injections in
hip OA studies mostly showed a peak effect after 1–3 weeks,
but still showed significant pain reduction at 8–12 weeks
follow-up.18 21–23 In a recent Cochrane review on IA glucocor-
ticoid injections in knee OA, the effects were moderate at 1–2
weeks after treatment (effect size 0.48), small to moderate at 4–6
weeks (effect size 0.41) and small at 13 weeks after treatment
(effect size 0.22).24 Therefore, our findings should be replicated
in future research.
Also, a surprising finding was that, for patients’ perceived
improvement and the OMERACT-OARSI responders, there
was a significant association in favour of glucocorticoid injec-
tion only at a 2-week follow-up. There are two possible expla-
nations for this. First, for patients’ perceived improvement we
dichotomised the 7-point Likert scale, which resulted in less
power. Second, the answer options we provided in the ques-
tionnaire were not clearly formulated. For example, answer
options were ‘completely recovered’, ‘almost completely recov-
ered’ and ‘slightly recovered’, resulting in a large step between
‘almost completely recovered’ and ‘slightly recovered’. A better
delineation would have been: ‘completely improved’, ‘markedly
improved’ and ‘slightly improved’.
In our RCT, we gave a single IM glucocorticoid injection. In
clinical practice, patients are sometimes offered multiple IA injec-
tions per year. A recent trial in patients with knee OA showed
that three monthly injection with glucocorticoid in the knee joint
during 2 years resulted in a significantly greater cartilage volume
loss than did saline injection.25 However, there are concerns
that even one IA glucocorticoid injection may cause toxicity to
chondrocytes, possibly resulting in progression of OA. This has
been confirmed in in vitro and in vivo animal studies and needs
further study in humans.26 27 It is unknown whether a single IM
glucocorticoid injection has a negative effect on chondrocytes.
The effect of an IA glucocorticoid injection for pain reduction
in hip OA has been reported in several RCTs.18 21–23 The present
study shows that systemic treatment with an IM glucocorticoid
injection is effective compared with placebo on pain reduction
in patients with hip OA. The administration of an IM injection
is much easier than an IA hip joint injection without the need for
ultrasound/radiologic guidance and can, therefore, be performed
in both secondary and primary care. However, the comparative
effectiveness of an IM injection compared with an IA injection
is unknown.
strengths and limitations
An important strength of our placebo RCT is that it was
blinded for outcome assessors, patients, treating physicians, and
researchers (including the statistical analyses). Second, we had
Figure 2 Pain score in rest during the follow-up of glucocorticoid and placebo group. Data shown as mean; SE of the mean (see the online
supplementary table S3 for data). NRS, Numerical Rating Scale.
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881Dorleijn DMJ, et al. Ann Rheum Dis 2018;77:875–882. doi:10.1136/annrheumdis-2017-212628
Clinical and epidemiological research
a high follow-up rate, that is, 100% at 2 weeks in both groups,
which was the primary outcome time point. At a 12-week
follow-up, the follow-up rate was 98% in the glucocorticoid
injection group and 94% in the placebo group.
A limitation was not including 128 participants. Nevertheless,
we were still able to significantly detect a 10-point difference on
a 0–100 scale that was beforehand assumed to be the minimal
clinically important difference.
A total of 92 patients (22%) declined to participate, because
they did not want to risk receiving a placebo. Similarly, Lambert
et al found that almost 50% of their patients refused to partici-
pate to avoid the risk of placebo treatment.23 Second, although
our patients reported moderate to severe pain (NRS ≥3), the
main exclusion reason was that they had not used any analgesics
during the past 3 weeks. It would be interesting to establish why
patients with moderate to severe pain do not take analgesics. For
hip OA little is known about patients’ preference and percep-
tions on treatment. In knee OA, although about 75% of patients
use over-the-counter oral analgesics, they do not perceive this
treatment as being the most effective; instead, patients perceived
viscosupplementation (74.1%), narcotics (67.8%) and steroid
injection (67.6%) as being the most effective.28
To exclude patients with other painful hip diseases, we set
strict criteria for the presence of radiological hip OA (KL ≥2).
A final point was the exclusion of patients with diabetes
mellitus, a frequently occurring comorbidity in this patient
population. It is well known that glucocorticoids can give t
ab
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%
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s
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95
%
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I
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e
Pe
rc
ei
ve
d
im
pr
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em
en
t*
30
(5
8)
17
(3
2)
1.
7
1.
1
to
2
.7
0.
02
25
(4
8)
15
(2
8)
1.
6
1.
0
to
2
.8
0.
06
23
(4
4)
17
(3
2)
1.
4
0.
8
to
2
.2
0.
23
22
(4
2)
16
(3
0)
1.
3
0.
8
to
2
.1
0.
37
Re
sp
on
de
r†
24
(4
6)
12
(2
2)
2.
0
1.
1
to
3
.6
0.
03
21
(4
0)
15
(2
8)
1.
5
0.
8
to
2
.
5
0.
23
23
(4
4)
16
(3
0)
1.
5
0.
9
to
2
.5
0.
15
22
(4
2)
17
(3
2)
1.
2
0.
7
to
2
.7
0.
47
Va
lu
es
a
re
n
(%
);
an
al
ys
es
a
dj
us
te
d
fo
r
KL
-s
co
re
a
t
ba
se
lin
e,
e
th
ni
ci
ty
, m
or
ni
ng
s
tif
fn
es
s
an
d
pa
tie
nt
s
ex
pe
ct
ed
e
ff
ec
t
of
in
je
ct
io
n
an
d
fo
r
th
e
ba
se
lin
e
va
lu
e
of
t
he
o
ut
co
m
e
of
in
te
re
st
; c
or
tic
os
te
ro
id
g
ro
up
n
=
52
; p
la
ce
bo
g
ro
up
n
=
54
.
*P
er
ce
iv
ed
im
pr
ov
em
en
t
in
di
ca
te
s
sc
or
es
c
om
pl
et
el
y
im
pr
ov
ed
, s
ig
ni
fic
an
tly
im
pr
ov
ed
a
nd
s
lig
ht
ly
im
pr
ov
ed
.
†A
cc
or
di
ng
t
o
th
e
O
M
ER
A
C
T-
O
A
RS
I c
rit
er
ia
.
C
C
S,
g
lu
co
co
rt
ic
oi
d;
G
EE
, g
en
er
al
is
ed
e
st
im
at
in
g
eq
ua
tio
ns
; R
R,
r
el
at
iv
e
ris
k.
R
an
ge
m
is
si
ng
v
al
ue
s:
n
=
0
at
b
as
el
in
e
an
d
a
2-
w
ee
k
fo
llo
w
-u
p
to
n
=
4
at
a
1
2-
w
ee
k
fo
llo
w
-u
p.
table 4 Adverse events in the two study groups at a 2-week
follow-up
Adverse events by organ system*
Glucocorticoid
(n=52)
Placebo
(n=54)
Reproductive system and breast disorders
Hot flushes 8 (15) 4 (7)
Irregular menstruation 0 0
Immune system disorders
Itching 4 (8) 1 (2)
Urticaria 1 (2) 0
Respiratory, thoracic and mediastinal disorders
Dyspnoea 0 1 (2)
Epistaxis 1 (2) 0
Nervous system disorders
Headache 5 (10) 4 (7)
Cramp 2 (4) 0
Paresthesia 0 1 (2)
Sweating 2 (4) 0
Musculoskeletal and connective tissue disorder
Pain in extremity 2 (4) 2 (4)
Gastrointestinal disorders
Bowel complaints 0 1 (2)
Nausea 0 1 (2)
General disorders and administration site
condition
Pain 2 (4) 0
Fatigue 0 1 (2)
Psychiatric disorders
Agitation 0 1 (2)
Nervous 0 1 (2)
Values in n (%).
*Classified according to Common Terminology Criteria for Adverse Events Version
4.0, National Institutes of Health National Cancer Institute.
882 Dorleijn DMJ, et al. Ann Rheum Dis 2018;77:875–882. doi:10.1136/annrheumdis-2017-212628
Clinical and epidemiological research
rise to hyperglycaemia in diabetic patients.29 For reasons of
patient safety, our medical ethics committee stipulated that we
excluded diabetic patients from the present trial; this means
that we cannot extrapolate our results to patients with diabetes
and hip OA.
Based on the present results, we conclude that an IM gluco-
corticoid injection showed effectiveness in patients with hip OA
in only one of the three primary outcomes at 2-weeks post-injec-
tion, but that all primary outcomes and almost all secondary pain
and function outcomes showed effectiveness from 4 to 6 weeks
that lasted for the entire 12-week follow-up.
Contributors dMJd: trial coordination, data-acquisition, data-analysis and data
interpretation, writing article. pAJL: study design, participation in trial coordination,
data interpretation and extensive review of article. Mr, MK, JAnV and pJEB: study
design and review of article. pKB: study design, radiological assessment, data
interpretation and review of article. SMAB-Z: conceived the study, study design, data
interpretation and extensive review of article. All authors read and approved the final
manuscript.
Funding Financial support was received from the dutch Arthritis Foundation and
the nutsohra Fund.
disclaimer there was no role of both funding sources.
Competing interests MK reports grants from Abbvie, grants from Levicept, grants
from GlaxoSmithKline, grants from Arthritis rheumatology, grants from ApproACH
consortium, grants from Foreum, grants from tI-pharma, grants from pfizer; outside
the submitted work. SMAB-Z reports grants from dutch Arthritis Foundation, grants
from nuts ohra, during the conduct of the study. pending grants from dutch Arthritis
Foundation, at the netherlands organization for Health research and development,
and EU Horizon 2020, outside the submitted work. Grants received from the dutch
Arthritis Foundation, netherlands organization for Health research and development,
nuts-ohra, and EU Fp7, outside the submitted work.
Patient consent obtained.
ethics approval Medical Ethics Committee of the Erasmus University Medical
Center.
Provenance and peer review not commissioned; externally peer reviewed.
© Article author(s) (or their employer(s) unless otherwise stated in the text of the
article) 2018. All rights reserved. no commercial use is permitted unless otherwise
expressly granted.
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Reproduced with permission of copyright owner. Further reproduction
prohibited without permission.
Abstract
Introduction
Methods
Trial design
Patients
Interventions
Randomisation
Blinding
Outcomes
Sample size
Statistical analysis
Results
Patient flow
Recruitment
Lost to follow-up
Patient population
Primary outcomes
Secondary outcomes
Adverse events and medical consumption
Ancillary analyses
Discussion
Strengths and limitations
References
875Dorleijn DMJ, et al. Ann Rheum Dis 2018;77:875–882. doi:10.1136/annrheumdis-2017-212628
Clinical and epidemiological research
ExtEndEd rEport
Intramuscular glucocorticoid injection versus placebo
injection in hip osteoarthritis: a 12-week blinded
randomised controlled trial
desirée M J dorleijn,1 pim A J Luijsterburg,1 Max reijman,2 Margreet Kloppenburg,3
Jan A n Verhaar,2 patrick J E Bindels,1 pieter Koen Bos,2 Sita M A Bierma-Zeinstra1,2
AbstrACt
Objectives Guidelines recommend intra-articular
glucocorticoid injection in patients with painful hip
osteoarthritis. However, intra-articular hip injection
is an invasive procedure. the efficacy of systemic
glucocorticoid treatment for pain reduction in
hip osteoarthritis is unknown. this randomised,
double-blind, trial assessed effectiveness in hip pain
reduction of an intramuscular glucocorticoid injection
compared with a placebo injection in patients with hip
osteoarthritis.
Methods patients with painful hip osteoarthritis were
randomised to either 40 mg triamcinolone acetate or
placebo with an intramuscular injection into the gluteus
muscle. the primary outcomes were severity of hip pain
at rest, during walking (0–10) and WoMAC pain at
2-week postinjection. We used linear mixed models for
repeated measurements at 2, 4, 6 and 12 weeks for the
intention-to-treat data analysis.
results of the 107 patients randomised, 106 could
be analysed (52 in the glucocorticoid group, 54 in the
placebo group). At 2-week follow-up, compared with
placebo injection, the intramuscular glucocorticoid
injection showed a significant and clinically relevant
difference in hip pain reduction at rest (difference −1.3,
95% CI −2.3 to −0.3). this effect persisted for the entire
12-week follow-up. For hip pain during walking, the
effect was present at 4-week, 6-week and 12-week
follow-ups, and for WoMAC pain the effect was present
at 6-week and 12-week follow-u
p.
Conclusions An intramuscular glucocorticoid injection
showed effectiveness in patients with hip osteoarthritis
on one of the three primary outcomes at 2-week
postinjection. All primary outcomes showed effectiveness
from 4 to 6 weeks, up to a 12-week follow-up.
trial registration number ntr2966.
IntrOduCtIOn
Several international guidelines recommend
intra-articular (IA) glucocorticoid injections for
patients with hip osteoarthritis (OA) experiencing
moderate to severe pain and not responding to oral
analgesics.1–3 A systematic review on the efficacy of
intra-articular steroids in moderate/severe hip OA
included five randomised controlled trials (RCT)
and the assessed quality of the studies was high.4
The treatment effect was large at 1 week post-in-
jection, but declined afterwards. At 8 weeks, there
were two trials that reported a reduction in pain
with a moderate effect size.4
However, injection into the hip joint is chal-
lenging because the joint cannot be palpated and
is adjacent to important neurovascular structures.
An IA hip injection is best performed under fluoro-
scopic or ultrasound guidance.
A serious side effect of an IA injection is a septic
arthritis. The incidence of this side effect is very low,
and scarce in the available literature. A systematic
review and meta-analysis of IA injection in knee OA
comparing effectiveness of pharmacological inter-
ventions included 29 studies (3152 patients, 9500
IA glucocorticoid injections) and reported only 1
septic arthritis (in the IA placebo group).5
A systemic effect of glucocorticoids on joint pain
has been indicated in patients with subacromial
impingement shoulder pain. A double-blinded RCT
showed no important differences in effectiveness
on pain of ultrasound-guided subacromial gluco-
corticoid injection compared with gluteal injec-
tion.6 A systemic effect of glucocorticoids was also
suggested in an RCT reporting the effect of local
glucocorticoid injection for greater trochanteric
pain syndrome: patients with concurrent hip OA or
chronic low back pain had an equal or even more
pronounced decrease in pain.7 8
If an intramuscular (IM) glucocorticoid injection
is shown to have a clinically relevant effect on pain,
this would offer a less complex alternative treatment
for episodes of increased pain in hip OA. Therefore,
this study assessed the efficacy of an IM glucocorti-
coid injection compared with an IM placebo injec-
tion on hip pain severity in patients with hip OA
who were not responding to oral analgesics.
MethOds
trial design
This was a multicentre, double-blinded, randomised
controlled superiority trial with two parallel groups
and a follow-up period of 12 weeks: details of
the study protocol were published earlier.9 10 The
Medical Ethics Committee of the Erasmus Univer-
sity Medical Centre (EMC; Rotterdam) approved
the study protocol (MEC2011-115) and all included
patients provided written informed consent.
Patients
Patients with hip OA were invited to participate in
the trial by general practitioners and orthopaedic
surgeons located in the south-west of the Nether-
lands. Patients (aged >40 years) were eligible for
inclusion if they met the American College for
to cite: dorleijn dMJ,
Luijsterburg pAJ, reijman M,
et al. Ann Rheum Dis
2018;77:875–882.
handling editor Josef S
Smolen
► Additional material is
published online only. to view
please visit the journal online
(http:// dx. doi. org/ 10. 1136/
annrheumdis- 2017- 212628).
1department of General
practice, Erasmus MC University
Medical Center rotterdam,
rotterdam, the netherlands
2department of orthopaedics,
Erasmus MC University Medical
Center rotterdam, rotterdam,
the netherlands
3department of rheumatology,
Leiden University Medical
Center, rotterdam, the
netherlands
Correspondence to
desirée M J dorleijn,
department of General practice,
Erasmus MC University Medical
Center rotterdam, rotterdam
3000 CA, the netherlands;
d. dorleijn@ erasmusmc. nl
received 1 november 2017
revised 17 February 2018
Accepted 18 February 2018
published online First
7 March 2018
http://www.eular.org/
http://ard.bmj.com/
www.trialregister.nl
http://crossmark.crossref.org/dialog/?doi=10.1136/annrheumdis-2017-212628&domain=pdf&date_stamp=2018-05-08
876 Dorleijn DMJ, et al. Ann Rheum Dis 2018;77:875–882. doi:10.1136/annrheumdis-2017-212628
Clinical and epidemiological research
Rheumatology (ACR) clinical criteria for hip OA during clinical
screening and radiological evidence of hip OA was present (Kell-
gren & Lawrence ‘score’ (KL) ≥2).11 12 Patients were included if
they had symptomatic disease for ≥6 months, and had moderate
to severe hip pain score ≥3 (scale 0–10; 0=no pain) despite the
use of oral analgesics at time of inclusion.
Radiological hip OA was scored on an anterior–posterior
pelvic radiograph of (at most) 6-month old. The radiological
grade of hip OA was scored by two researchers (DD, PKB)
independently and the interobserver reliability was κ=0.7 for
KL <2 vs KL ≥2. In case of disagreement, a consensus was
formed during a consensus meeting. If a patient had bilateral hip
OA, the more painful hip was selected as the study hip.
Patients were excluded if they had diabetes mellitus, were
using oral glucocorticoids, had local/systemic infection, had
presence of inflammatory rheumatic diseases (eg, rheumatoid
arthritis, psoriatic arthritis and spondylarthropathies), coagulop-
athy, used coumarins, had a gastric ulcer, allergy to glucocorti-
coids, radiological signs of osteonecrosis, had an IA injection in
the hip in the previous 6 months, were on the waiting list for
total hip replacement (THR) surgery or were unable to complete
questionnaires in Dutch.
Interventions
Patients received either 40 mg triamcinolone acetate (1 mL)
or 1 mL normal saline (placebo) with an IM injection. At the
research centre, the trial nurse administered the allocated injec-
tion in the upper lateral quadrant of the gluteal musculature on
the ipsilateral side of the study hip.
randomisation
An independent pharmacy assistant allocated each included
patient based on a computerised randomisation list using random
blocks of 2 and 4 to either placebo (saline) injection or triamcin-
olone acetate 40 mg injection. Randomisation was stratified for
setting (general practice and orthopaedic outpatient clinic). After
randomisation, the vials for the injections were prepared, packed
and sealed in an identical way for both groups by the pharmacy
of the EMC. The randomisation list was available only to the
pharmacy assistant.
blinding
In this trial, the outcome assessors, patients, treating physicians,
researchers (including the statistical analyses) and research assis-
tants involved in data collection were blinded to the content of
the injections. Since normal saline is transparent and triamcin-
olone acetate is a white solution, the independent nurse who
prepared and injected the injection was non-blinded. To assure
blinding of the others, the independent trial nurse prepared and
administered the injection out of sight of the patient, assessors,
treating physicians and the researchers. This trial nurse was not
involved with follow-up measurements. After preparation and
before injection, the syringe was covered with an opaque foil to
assure blinding of the patient.
Outcom
es
The primary outcomes were severity of hip pain at 2-week post-
injection measured on an 11-point numerical rating scale (NRS:
0–10, 0=no pain) at rest and during walking, and measured
with the Western Ontario and McMaster University Osteoar-
thritis Index pain subscale (WOMAC pain: 0–100, 0=no symp-
toms).13 14
Secondary outcomes were the primary outcomes at 4-week,
6-week and 12-week follow-ups. Additional secondary outcome
measures were WOMAC function and stiffness, WOMAC total
score, Hip disability and Osteoarthritis Outcome Score for pain
(HOOS pain), quality of life (EQ-5D), Intermittent and Constant
Osteoarthritis Pain (ICOAP) and patients’ perceived recovery
assessed on a 7-point Likert scale.15–17 At all time points, the
WOMAC and ICOAP scales are presented as normalised scores
(0–100, 0=no symptoms). The HOOS subscale is presented as
normalised score (0–100, 100=no symptoms). Also recorded
was patients’ medical consumption, including analgesic use and
adverse reactions at all time points. Patients were allowed to use
escape pain medication as needed.
Another secondary outcome was the percentage of responders
as defined by the OMERACT-OARSI criteria (improvement in at
least two of the three following domains: ≥20% improvement
in WOMAC pain, ≥20% improvement in WOMAC function
and markedly improved on patients’ global assessment).16 For
patients’ global assessment the 7-point Likert scale for patients’
perceived recovery was dichotomised in ‘improved’ (scores:
completely recovered, almost completely recovered and slightly
recovered) and ‘not improved’ (scores: no change, slightly
worse, significantly worsened and worse than ever).
At baseline and at a 12-week follow-up, patients visited the
research centre to undergo a physical examination of hips, spine
and knees. At baseline, blood samples were collected to measure
the erythrocyte sedimentation rate and C reactive protein to gain
insight in the inflammatory processes.14
sample siz
e
Power calculations were based on a study with similar inclusion
criteria.18 A 10-point difference (SD 20) on hip pain at rest and
during walking (visual analogue scale: 0–100) was assumed to
be the minimal clinically important difference between both
groups.19 The accompanying effect size of 0.5 is from the clinical
standpoint a moderate effect and in general considered clinically
relevant.20 For our study, this implies one point on the NRS pain
scale. With a power of 80% and an alpha of 5%, 64 patients
per group were required (including 5% loss to follow-up=67
patients per group). The same sample size was needed when an
8-point difference (SD 16) on the standardised WOMAC total
score and pain subscale score (0–100) was assumed as a clinically
relevant difference between the groups.
statistical analysis
The intention-to-treat principle was used. Descriptive statistics
were used to describe patients’ characteristics at baseline, items
of physical examination and the severity of radiologic hip OA.
Linear mixed models with repeated measures were used for
continuous outcomes. When patients underwent a THR, data of
these patients were included up to the date of surgery. To model
the covariance of repeated measures by patients, the option for
data structure in the analyses was set on ‘unstructured’, because
this yielded the lowest Akaike’s information criterion. Fixed
effects were time and time by treatment. Analyses were adjusted
for baseline variables and for the baseline value of the outcome
of interest.9 Therefore, at a 2-week follow-up presented are the
outcomes at 2 weeks, corrected for baseline scores. At 4 weeks,
presented are the results at a 4-week follow-up time point,
corrected for baseline and 2 weeks scores and so on.
Generalised estimating equations (GEE) analyses with repeated
measures were performed for the dichotomous outcomes
perceived improvement, and the OMERACT-OARSI responder.
877Dorleijn DMJ, et al. Ann Rheum Dis 2018;77:875–882. doi:10.1136/annrheumdis-2017-212628
Clinical and epidemiological research
Before GEE analyses, multiple imputations were performed for
missing values, creating 100 imputed datasets.
The Pearson χ2 test was used to analyse differences between
groups concerning medical consumption, analgesic use and
adverse events. An explorative, predefined, subgroup analysis
was performed assessing the interaction effects between injec-
tions and setting on the primary outcomes.
9
All analyses were performed using SPSS V.24.
results
Patient flow
A total of 422 invited patients contacted the research centre and
were screened for eligibility; of these, 92 refused to participate
and 223 did not meet the inclusion criteria (figure 1).
Finally, 107 patients provided informed consent: 53 were
randomised to the glucocorticoid injection and 54 to the placebo
injection. One patient in the glucocorticoid group withdrew his
consent just before the appointment for baseline physical exam-
ination and subsequent injection, because his pain had resolved
spontaneously. Because this patient did not receive the allocated
treatment and was not willing to send us the completed base-
line questionnaire or any follow-up questionnaires, he was not
included in the analyses.
recruitment
Recruitment of patients took place between September 2011
and October 2014 and follow-up measurements were done until
January 2015. Of the 107 included patients, general practi-
tioners referred 81 patients.
lost to follow-u
p
At a 6-week follow-up, one patient in the glucocorticoid group
reported being scheduled for a THR; in the placebo group two
patients (at 4-week and 6-week follow-up, respectively) reported
being scheduled for a THR. One patient in the placebo group
was not willing to participate after 6 weeks due to logistical
problems.
Patient population
Of all patients, 52 received the allocated glucocorticoid injec-
tion and 54 the allocated placebo injection, and were included
in the analyses. Baseline characteristics of both patient groups
are presented in table 1. Of the 106 patients, 73 (68%) were
women; the mean age was 64 (SD 11) years, and the duration of
hip OA symptoms was ≥1 year for 74 (70%) patients.
Figure 1 Flow diagram of the study participants. NRS, Numerical Rating Scale (0–10; 0=no pain); FU, follow -up; IA, intra-articular; KL, Kellgren &
Lawrence ‘score’ for hip osteoarthritis; THR, total hip replacement; wks, weeks.
878 Dorleijn DMJ, et al. Ann Rheum Dis 2018;77:875–882. doi:10.1136/annrheumdis-2017-212628
Clinical and epidemiological research
The KL score of hip OA at baseline, ethnicity, morning hip
stiffness and patients’ expected effect of the injection changed
the estimates for the primary outcome ≥10%. We adjusted for
these baseline variables in the statistical analyses.
Primary outcomes
At a 2-week follow-up, compared with the placebo injection,
the glucocorticoid injection showed a significant association
with hip pain reduction at rest (between group difference −1.3,
95% CI −2.3 to −0.3) (table 2 and figure 2). Also, at a 2-week
follow-up, there were no significant associations between gluco-
corticoid injection and hip pain during walking (difference
−0.9, 95% CI −1.9 to 0.1) and WOMAC pain (difference −6.1,
95% CI −13.4 to 1.2). The correlation between the primary
endpoints ranged from r 0.64 to r 0.84. The results of the unad-
justed linear mixed model analysis were similar (online supple-
mentary table S1).
secondary outcomes
At 4-week, 6-week and 12-week follow-ups, the glucocorticoid
injection was associated with a significant hip pain reduction
at rest and during walking (table 2 and figure 2). Moreover,
at almost all follow-up measurements, the estimates showed
significant differences in favour of the glucocorticoid injec-
tion on WOMAC pain, function, stiffness and total; HOOS
pain; and ICOAP total, intermittent and constant. No signifi-
cant differences between groups were found for quality of life
(table 2). At a 2-week follow-up, perceived improvement and
table 1 Patients’ characteristics at baseline
Characteristic
Glucocorticoid
(n=52)
Placebo
(n=54)
Age, years, mean±SD 66±11 63±10
Body mass index, kg/m2, mean±SD 27±3.7 28±6.4
Women, n(%) 40 (77) 33 (61)
Duration of symptoms, n(%) ≥1 year 40 (77) 34 (63)
Referral to study by, n(%) General practitioner 39 (75) 41 (76)
Kellgren & Lawrence score hip OA, n(%) KL 2 42 (81) 38 (70)
Ethnicity Dutch, n(%) 51 (98) 47 (87)
Employment, n(%) 17 (33) 23 (43)
Comorbidities
Osteoarthritis of knee(s), n(%) 20 (39) 15 (28)
Osteoarthritis of hand(s), n(%) 12 (23) 14 (26)
Low back pain, n(%) 33 (64) 30 (56)
Signs and symptoms
Stiffness of the hip, n(%) Morning stiffness 40 (77) 35 (65)
Severity of hip pain last week NRS 0–10, mean±SD Pain at rest 4.3±2.4 4.2±2.5
Pain at walking 5.4±2.1 5.1±2.3
WOMAC 0–100, mean±SD Total score 46±19 47±18
Pain 43±17 43±17
Function 47±20 48±19
Stiffness 52±21 48±24
HOOS 0–100, mean±SD Pain 52±17 52±16
ICOAP 0–100, mean±SD Total score 38±18 39±17
Intermittent pain 41±21 41±17
Continuous pain 34±21 36±19
EQ-5D score, mean±SD 0.66±0.23 0.68±0.26
Treatment
Frequent pain medication use*, n(%) Acetaminophen 25 (48) 26 (48)
NSAID 14 (27) 14 (26)
Opiates 8 (15) 6 (11)
Visited healthcare giver for hip OA in the previous
3 months, n(%)
General practitioner
n of visits (median, IQR)
24 (46)
1 (1)
22 (41)
1 (0)
Physiotherapist
n of visits (median, IQR)
14 (27)
6 (11)
22 (41)
6 (5)
Medical specialist
n of visits (median, IQR)
16 (31)
1 (0)
18 (33)
1 (0.3)
Patient’s expected effect of injection, n(%) Much or very much 36 (69) 29 (54)
Laboratory outcomes
CRP, median (IQR) 2 (3.1) 1.5 (3.4)
ESR, median (IQR) 9.5 (13) 10 (12)
*Frequent pain medication use=3–5 times/week or daily use in the past 3 weeks.
ADL, function in daily living; CRP, C reactive protein; EQ-5D, Euroqol; ESR, erythrocyte sedimentation rate; HOOS, Hip Disability and Osteoarthritis Outcome Score (0=extreme
problems); ICOAP, Intermittent and Constant Osteoarthritis Pain (0=no pain); KL, Kellgren & Lawrence grading of radiologic hip OA; NRS, Numeric Rating Scale (0=no pain); NSAID,
non-steroidal anti-inflammatory drug; OA, osteoarthritis; WOMAC, Western Ontario and McMaster University Osteoarthritis Index (0=no pain).
https://dx.doi.org/10.1136/annrheumdis-2017-212628
https://dx.doi.org/10.1136/annrheumdis-2017-212628
879Dorleijn DMJ, et al. Ann Rheum Dis 2018;77:875–882. doi:10.1136/annrheumdis-2017-212628
Clinical and epidemiological research
ta
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2
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)
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−
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p
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n
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39 (1
7)
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1
−
13
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to
1
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10
34 (1
9)
39 (1
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32 (1
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la
ce
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g
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up
is
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re
nc
e
gr
ou
p.
Va
lu
es
in
m
ea
n
(S
D)
; N
RS
p
re
se
nt
ed
a
s
0–
10
s
co
re
; W
O
M
AC
a
nd
IC
O
AP
p
re
se
nt
ed
a
s
0–
10
0
sc
or
e;
m
od
el
a
dj
us
te
d
fo
r K
L-
sc
or
e
at
b
as
el
in
e,
e
th
ni
ci
ty
, m
or
ni
ng
s
tif
fn
es
s
an
d
pa
tie
nt
s’
e
xp
ec
te
d
ef
fe
ct
o
f i
nj
ec
tio
n
an
d
fo
r t
he
b
as
el
in
e
va
lu
e
of
th
e
ou
tc
om
e
of
in
te
re
st
; g
lu
co
co
rt
ic
oi
d
gr
ou
p
n=
52
; p
la
ce
bo
g
ro
up
n=
54
.
Ra
ng
e
m
is
si
ng
v
al
ue
s:
n
=
0
a
t b
as
el
in
e
an
d
2-
w
ee
k
fo
llo
w
-u
p
to
n
=
4
a
t 1
2-
w
ee
k
fo
llo
w
-u
p.
Δ
, b
et
w
ee
n
gr
ou
p
di
ffe
re
nc
e;
C
CS
, g
lu
co
co
rt
ic
oi
d;
E
Q
-5
D,
E
ur
oQ
ol
fi
ve
d
im
en
si
on
s
ca
le
; H
O
O
S,
H
ip
d
is
ab
ili
ty
a
nd
O
st
eo
ar
th
rit
is
O
ut
co
m
e
Sc
or
e
(0
=
ex
tr
em
e
pr
ob
le
m
s)
; I
CO
AP
, I
nt
er
m
itt
en
t a
nd
C
on
st
an
t O
st
eo
ar
th
rit
is
P
ai
n;
N
RS
, N
um
er
ic
al
R
at
in
g
Sc
al
e
(0
=
no
p
ai
n)
; W
O
M
AC
, W
es
te
rn
O
nt
ar
io
a
nd
M
cM
as
te
r
U
ni
ve
rs
iti
es
In
de
x
(0
=
n
o
pa
in
).
880 Dorleijn DMJ, et al. Ann Rheum Dis 2018;77:875–882. doi:10.1136/annrheumdis-2017-212628
Clinical and epidemiological research
the OMERACT-OARSI responders showed a significant effect in
favour of glucocorticoid injection: RR 1.7 (95% CI 1.1 to 2.7)
and 2.0 (95% CI 1.1 to 3.6), respectively (table 3).
Adverse events and medical consumption
In the glucocorticoid group, 19 patients reported 27 adverse
events. In the placebo group 13 patients reported 18 adverse
events. All adverse events were classified as non-serious (table 4).
Hot flushes, headache and itching were reported most frequently
in the glucocorticoid group. There were no significant differences
in medical consumption between the two groups (online supple-
mentary table S2).
Ancillary analyses
In the explorative subgroup analyses, the results of the interac-
tion of setting on injections showed no significant differences
between the two groups (NRS at rest 1.5, 95% CI −0.6 to 3.7).
dIsCussIOn
We found that an IM glucocorticoid injection showed effec-
tiveness in patients with hip OA on one of the three primary
outcomes at a 2-weeks postinjection and that the effect is prob-
ably clinically relevant. All primary outcomes and almost all
secondary pain and function outcomes showed effectiveness
from 4 to 6 weeks that lasted for the entire 12- weeks follow-up.
The highest effects were seen at 4–12 weeks follow-up instead of
at the expected 2-weeks follow-up.
In this study, three primary endpoints were used. This
increases the risk of a type 1 error. However, with a bonfer-
roni correction for the three primary outcomes (p<0.017) pain
at rest was still significantly associated with pain reduction at
a 2-week follow-up.
It was surprising that hip pain reduction after IM glucocor-
ticoid injection was still present at a similar degree at 12-week
follow-up. Previous studies on IA glucocorticoid injections in
hip OA studies mostly showed a peak effect after 1–3 weeks,
but still showed significant pain reduction at 8–12 weeks
follow-up.18 21–23 In a recent Cochrane review on IA glucocor-
ticoid injections in knee OA, the effects were moderate at 1–2
weeks after treatment (effect size 0.48), small to moderate at 4–6
weeks (effect size 0.41) and small at 13 weeks after treatment
(effect size 0.22).24 Therefore, our findings should be replicated
in future research.
Also, a surprising finding was that, for patients’ perceived
improvement and the OMERACT-OARSI responders, there
was a significant association in favour of glucocorticoid injec-
tion only at a 2-week follow-up. There are two possible expla-
nations for this. First, for patients’ perceived improvement we
dichotomised the 7-point Likert scale, which resulted in less
power. Second, the answer options we provided in the ques-
tionnaire were not clearly formulated. For example, answer
options were ‘completely recovered’, ‘almost completely recov-
ered’ and ‘slightly recovered’, resulting in a large step between
‘almost completely recovered’ and ‘slightly recovered’. A better
delineation would have been: ‘completely improved’, ‘markedly
improved’ and ‘slightly improved’.
In our RCT, we gave a single IM glucocorticoid injection. In
clinical practice, patients are sometimes offered multiple IA injec-
tions per year. A recent trial in patients with knee OA showed
that three monthly injection with glucocorticoid in the knee joint
during 2 years resulted in a significantly greater cartilage volume
loss than did saline injection.25 However, there are concerns
that even one IA glucocorticoid injection may cause toxicity to
chondrocytes, possibly resulting in progression of OA. This has
been confirmed in in vitro and in vivo animal studies and needs
further study in humans.26 27 It is unknown whether a single IM
glucocorticoid injection has a negative effect on chondrocytes.
The effect of an IA glucocorticoid injection for pain reduction
in hip OA has been reported in several RCTs.18 21–23 The present
study shows that systemic treatment with an IM glucocorticoid
injection is effective compared with placebo on pain reduction
in patients with hip OA. The administration of an IM injection
is much easier than an IA hip joint injection without the need for
ultrasound/radiologic guidance and can, therefore, be performed
in both secondary and primary care. However, the comparative
effectiveness of an IM injection compared with an IA injection
is unknown.
strengths and limitations
An important strength of our placebo RCT is that it was
blinded for outcome assessors, patients, treating physicians, and
researchers (including the statistical analyses). Second, we had
Figure 2 Pain score in rest during the follow-up of glucocorticoid and placebo group. Data shown as mean; SE of the mean (see the online
supplementary table S3 for data). NRS, Numerical Rating Scale.
https://dx.doi.org/10.1136/annrheumdis-2017-212628
https://dx.doi.org/10.1136/annrheumdis-2017-212628
https://dx.doi.org/10.1136/annrheumdis-2017-212628
881Dorleijn DMJ, et al. Ann Rheum Dis 2018;77:875–882. doi:10.1136/annrheumdis-2017-212628
Clinical and epidemiological research
a high follow-up rate, that is, 100% at 2 weeks in both groups,
which was the primary outcome time point. At a 12-week
follow-up, the follow-up rate was 98% in the glucocorticoid
injection group and 94% in the placebo group.
A limitation was not including 128 participants. Nevertheless,
we were still able to significantly detect a 10-point difference on
a 0–100 scale that was beforehand assumed to be the minimal
clinically important difference.
A total of 92 patients (22%) declined to participate, because
they did not want to risk receiving a placebo. Similarly, Lambert
et al found that almost 50% of their patients refused to partici-
pate to avoid the risk of placebo treatment.23 Second, although
our patients reported moderate to severe pain (NRS ≥3), the
main exclusion reason was that they had not used any analgesics
during the past 3 weeks. It would be interesting to establish why
patients with moderate to severe pain do not take analgesics. For
hip OA little is known about patients’ preference and percep-
tions on treatment. In knee OA, although about 75% of patients
use over-the-counter oral analgesics, they do not perceive this
treatment as being the most effective; instead, patients perceived
viscosupplementation (74.1%), narcotics (67.8%) and steroid
injection (67.6%) as being the most effective.28
To exclude patients with other painful hip diseases, we set
strict criteria for the presence of radiological hip OA (KL ≥2).
A final point was the exclusion of patients with diabetes
mellitus, a frequently occurring comorbidity in this patient
population. It is well known that glucocorticoids can give t
ab
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3
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(4
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37
Re
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24
(4
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(4
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47
Va
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(%
);
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r K
L-
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or
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r t
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; c
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=
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; p
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=
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.
*P
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tly
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†A
cc
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M
ER
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rit
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.
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R,
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n=
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4
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p.
table 4 Adverse events in the two study groups at a 2-week
follow-up
Adverse events by organ system*
Glucocorticoid
(n=52)
Placebo
(n=54)
Reproductive system and breast disorders
Hot flushes 8 (15) 4 (7)
Irregular menstruation 0 0
Immune system disorders
Itching 4 (8) 1 (2)
Urticaria 1 (2) 0
Respiratory, thoracic and mediastinal disorders
Dyspnoea 0 1 (2)
Epistaxis 1 (2) 0
Nervous system disorders
Headache 5 (10) 4 (7)
Cramp 2 (4) 0
Paresthesia 0 1 (2)
Sweating 2 (4) 0
Musculoskeletal and connective tissue disorder
Pain in extremity 2 (4) 2 (4)
Gastrointestinal disorders
Bowel complaints 0 1 (2)
Nausea 0 1 (2)
General disorders and administration site
condition
Pain 2 (4) 0
Fatigue 0 1 (2)
Psychiatric disorders
Agitation 0 1 (2)
Nervous 0 1 (2)
Values in n (%).
*Classified according to Common Terminology Criteria for Adverse Events Version
4.0, National Institutes of Health National Cancer Institute.
882 Dorleijn DMJ, et al. Ann Rheum Dis 2018;77:875–882. doi:10.1136/annrheumdis-2017-212628
Clinical and epidemiological research
rise to hyperglycaemia in diabetic patients.29 For reasons of
patient safety, our medical ethics committee stipulated that we
excluded diabetic patients from the present trial; this means
that we cannot extrapolate our results to patients with diabetes
and hip OA.
Based on the present results, we conclude that an IM gluco-
corticoid injection showed effectiveness in patients with hip OA
in only one of the three primary outcomes at 2-weeks post-injec-
tion, but that all primary outcomes and almost all secondary pain
and function outcomes showed effectiveness from 4 to 6 weeks
that lasted for the entire 12-week follow-up.
Contributors dMJd: trial coordination, data-acquisition, data-analysis and data
interpretation, writing article. pAJL: study design, participation in trial coordination,
data interpretation and extensive review of article. Mr, MK, JAnV and pJEB: study
design and review of article. pKB: study design, radiological assessment, data
interpretation and review of article. SMAB-Z: conceived the study, study design, data
interpretation and extensive review of article. All authors read and approved the final
manuscript.
Funding Financial support was received from the dutch Arthritis Foundation and
the nutsohra Fund.
disclaimer there was no role of both funding sources.
Competing interests MK reports grants from Abbvie, grants from Levicept, grants
from GlaxoSmithKline, grants from Arthritis rheumatology, grants from ApproACH
consortium, grants from Foreum, grants from tI-pharma, grants from pfizer; outside
the submitted work. SMAB-Z reports grants from dutch Arthritis Foundation, grants
from nuts ohra, during the conduct of the study. pending grants from dutch Arthritis
Foundation, at the netherlands organization for Health research and development,
and EU Horizon 2020, outside the submitted work. Grants received from the dutch
Arthritis Foundation, netherlands organization for Health research and development,
nuts-ohra, and EU Fp7, outside the submitted work.
Patient consent obtained.
ethics approval Medical Ethics Committee of the Erasmus University Medical
Center.
Provenance and peer review not commissioned; externally peer reviewed.
© Article author(s) (or their employer(s) unless otherwise stated in the text of the
article) 2018. All rights reserved. no commercial use is permitted unless otherwise
expressly granted.
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Reproduced with permission of copyright owner. Further reproduction
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Abstract
Introduction
Methods
Trial design
Patients
Interventions
Randomisation
Blinding
Outcomes
Sample size
Statistical analysis
Results
Patient flow
Recruitment
Lost to follow-up
Patient population
Primary outcomes
Secondary outcomes
Adverse events and medical consumption
Ancillary analyses
Discussion
Strengths and limitations
References
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RAPID CRITICAL APPRAISAL QUESTIONS FOR QUALITATIVE EVIDENCE |
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VALIDITY |
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1.Are the results of the study valid (i.e., trustworthy and credible)? |
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Unknown |
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a. How were study participants chosen? |
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b. How were accuracy and completeness of data assured? |
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c. How plausible/believable are the results? |
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i. Are implications of the research stated? |
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1. May new insights increase sensitivity to others’ needs? |
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2. May understandings enhance situational competence? |
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a. What is the effect on the reader? |
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1. Are results plausible and believable? |
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2. Is the reader imaginatively drawn into the experience? |
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RELIABILITY |
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2.What were the results? |
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a. Does the research approach fit the purpose of the study? |
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i. How does the researcher identify the study approach? |
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1. Are language and concepts consistent with the approach? |
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2. Are data collection and analysis techniques appropriate? |
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ii. Is the significance/importance of the study explicit? |
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1. Does review of the literature support a need for the study? |
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b. Is the phenomenon (human experience) clearly identified? |
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1. Does analysis guide direction of sampling and when it ends? |
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2. Are data management processes described? |
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c. What are the reported results (description or interpretation)? |
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i. How are specific findings presented? |
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1. Is presentation logical, consistent, and easy to follow? |
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2. Do quotes fit the findings they are intended to illustrate? |
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ii. How are overall results presented? |
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1. Are meanings derived from data described in context? |
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2. Does the writing effectively promote understanding? |
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APPLICABILITY |
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3. Will the results help me in caring for my patients? |
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a. Are the results relevant to persons in similar situations? |
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b. Are the results relevant to patient values and/or circumstances? |
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c. How may the results be applied in clinical practice? |
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Would you use the study results in your practice to make a difference in patient outcomes? •If yes, how? •If yes, why? •If no, why not? |
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Additional Comments/Reflections: Recommendation for article use within a body of evidence: |
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RAPID CRITICAL APPRAISAL QUESTIONS FOR RANDOMIZED CLINICAL TRIALS (RCTS) |
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VALIDITY |
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1. Are the results of the study valid? |
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a. Were the participants randomly assigned to the experimental and control groups? |
Yes |
No |
Unknown |
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b. Was random assignment concealed from the individuals who were first enrolling participants into the study? |
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c. Were the participants and providers blind to the study group? |
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d. Were reasons given to explain why participants did not complete the study? |
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e. Were the follow-up assessments conducted long enough to fully study the effects of the intervention? |
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f. Were the participants analyzed in the group to which they were randomly assigned? |
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g. Was the control group appropriate? |
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h. Were the instruments used to measure the outcomes valid and reliable? |
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i. Were the participants in each of the groups similar on demographic and baseline clinical variables? |
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RELIABILITY |
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2. What are the results? |
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a. How large is the intervention or treatment effect (NNT, NNH, effect size? |
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b. How precise is the intervention or treatment (CI)? |
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APPLICABILITY |
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3. Will the results help me in caring for my patients? |
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a. Were all clinically important outcomes measured? |
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b. What are the risks and benefits of the treatment? |
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c. Is the treatment feasible in my clinical setting? |
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d. What are my patient’s/family’s values and expectations for the outcome that is trying to be prevented and the treatment itself? |
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Would you use the study results in your practice to make a difference in patient outcomes? If yes, how? If yes, why? If no, why not? |
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Additional Comments/Reflections: |
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Recommendation for article use within a body of evidence: |
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