(2017) Socioeconomic and therapy factor influence on self‐reported fatigue, anxiety and depression in rheumatoid arthritis patients

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in rheuma
ARTICLE IN PRESSRBRE-361; No. of Pages 11
r e v b r a s r e u m a t o l . 2 0 1 7;x x x(x x):xxx–xxx
www.reumato logia .com.br
REVISTA BRASILEIRA DE
REUMATOLOGIA
Original article
Socioeconomic and therapy factor influence on
self-re
rheum
Mirjana
Snezˇana
a Primary H
b General Ho
c Pharmaceu
d Clinical Ce
e General Ho
a r t i c 
Article histor
Received 22
Accepted 20
Available on
Keywords:
Rheumatoid
Fatigue
Anxiety
Depression
Self-reporte
∗ Correspon
E-mail: b
http://dx.do
2255-5021/©
licenses/by-
 this article in press as: Lapcˇevic´ M, et al. Socioeconomic and therapy factor influence on self-reported fatigue, anxiety and depression
toid arthritis patients. Rev Bras Reumatol. 2017. http://dx.doi.org/10.1016/j.rbre.2017.02.004
ported fatigue, anxiety and depression in
atoid arthritis patients
 Lapcˇevic´ a, Mira Vukovic´ b, Branislav S. Gvozdenovic´ c,∗, Vesna Mioljevic´ d,
 Marjanovic´ e
ealthcare Center, Department of General Medicine, Belgrade, Serbia
spital Valjevo, Education Center, Belgrade, Serbia
tical Product Development Serbia, Pharmacovigilance Department, Belgrade, Serbia
nter of Serbia, Department of Hospital Epidemiology and Nutrition Hygiene, Belgrade, Serbia
spital Valjevo, Department of Psychiatry, Valjevo, Serbia
l e i n f o
y:
 March 2016
 December 2016
line xxx
 arthritis
d outcomes
a b s t r a c t
Introduction: Fatigue, anxiety and depression are very frequent symptoms in patients with
rheumatoid arthritis (RA).
Goals: In this study we evaluated the influence of socioeconomic characteristics, therapy and
comorbidities on the self-reported high fatigue, anxiety and depression in patients with RA.
Method: Multicenter cross-sectional study was performed in 22 health institutions in
Serbia during the period from April–August 2014 in population of older RA patients. Self-
reported patients health status was measured by: Fatigue Assessment Scale, Patient Health
Questionnaire-9 and Generalized Anxiety Disorder-7. Treatment modalities were defined
as: (1) non-steroidal anti-inflammatory drugs (NSAIDs) and/or analgesics and/or corti-
costeroids; (2) synthetic disease-modifying antirheumatic drugs (DMARDs) alone or in
combination with corticosteroids and/or NSAIDs and (3) any RA treatment which includes
biologic DMARDs.
Results: There were significant predictors of high depression: synthetic DMARDs therapy in
combination with corticosteroids and/or NSAIDs, physiotherapist self-payment, frequent
taxi use, alternative treatment and employment status. The need for another person’s assis-
tance, supplemental calcium therapy and professional qualifications were the predictors of
a high fatigue, whereas the age above 65 years had the protective effect on it. Anxiety was an
independent high fatigue predictor. The predictors of a high anxiety were: gastroprotection
with proton-pump inhibitors and patient occupation.
ding author.
gvozden@verat.net (B.S. Gvozdenovic´).
i.org/10.1016/j.rbre.2017.02.004
 2017 Elsevier Editora Ltda. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/
nc-nd/4.0/).
Please cite
in rheuma
ARTICLE IN PRESSRBRE-361; No. of Pages 11
2 r e v b r a s r e u m a t o l . 2 0 1 7;x x x(x x):xxx–xxx
Conclusion: Socioeconomic predictors of self-reported high depression, anxiety or fatigue
ntion
in a h
tal th
is is a
econ
torre
Palavras-cha
Artrite reum
Fadiga
Ansiedade
Depressão
Desfechos a
 e a d
-se 
orb
 AR
Introduct
Rheumatoi
inflammato
joint stiffn
treated the
manent de
first or seco
sis and an 
RA treatme
i.e. discont
synthetic D
or, if nece
months it i
low RA act
biologic DM
are different for each of the me
treatment they exclusively expla
nomic variables and supplemen
© 2017 Elsevier Editora Ltda. Th
Influência de fatores socio
ansiedade e depressão au
reumatoide
ve:
atoide
r e s u m o
Introduc¸ão: A fadiga, a ansiedade
com artrite reumatoide (AR).
Objetivos: Neste estudo, avaliou
acterísticas de tratamento e com
autorrelatadas em pacientes com
 this article in press as: Lapcˇevic´ M, et al. Socioeconomic and therapy factor in
toid arthritis patients. Rev Bras Reumatol. 2017. http://dx.doi.org/10.1016/j.r
utorrelatados Método: Este estudo transversal mu
Sérvia de abril a agosto de 2014 na 
saúde autorrelatado dos pacientes fo
Patient Health Questionnaire-9 e Genera
foram definidas como: 1) anti-inflam
corticosteroides; 2) fármacos antirreu
isoladamente ou em combinac¸ão com
para a AR que incluísse DMARD bioló
Resultados: Houve preditores signific
sintéticos em combinac¸ão com cortic
apia, uso frequente de servic¸os de
necessidade de assistência de outra
qualificac¸ões profissionais foram os p
teve um efeito protetor sobre a fadig
de fadiga elevada. Os preditores ans
da bomba de prótons e ocupac¸ão do 
Conclusão: Os preditores socioeconô
fadiga autorrelatadas são diferentes
acompanhados do tratamento básico
exclusivamente uma depressão eleva
cas e ao tratamento complementar, é
AR.
© 2017 Elsevier Editora L
BY-NC-ND
ion
d arthritis (RA) is a multifactorial systemic chronic
ry disease that primarily causes pain, swelling,
ess and loss of joint function.1 If not properly
 RA can cause joint damage including their per-
struction.2 The RA causes joint damage during the
nd year of the disease. That is why an early diagno-
adequate treatment of RA are very important. The
nt goal is the achievement of clinical remission,
inuation of the disease activity.3 By including one
isease-Modifying Antirheumatic Drug (DMARD)
ssary, two of them in combination during six
s expected to achieve the remission or at least the
ivity. If not achieved with synthetic DMARDs the
ARDs should also be included. Besides the afore-
mentioned
(NSAIDs) sh
needed, in
and improv
administra
sary to pro
inhibitors 
testinal ble
biochemica
to monitor 
during the 
Fatigue 
wide range
internation
hasn’t been
overwhelm
ed outcomes, while accompanied with the basic RA
igh depression. The anxiety, jointed with the socioeco-
erapy, is a significant fatigue predictor in RA patients.
n open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
ômicos e de tratamento sobre a fadiga,
latadas em pacientes com artrite
epressão são sintomas muito frequentes em pacientes
a influência de características socioeconômicas, car-
idades na elevac¸ão na fadiga, ansiedade e depressão
.
fluence on self-reported fatigue, anxiety and depression
bre.2017.02.004
lticêntrico foi feito em 22 instituic¸ões de saúde na
populac¸ão de pacientes idosos com AR. O status de
i medido pelos instrumentos Fatigue Assessment Scale,
lized Anxiety Disorder-7. As modalidades de tratamento
atórios não esteroides (AINE) e/ou analgésicos e/ou
máticos modificadores da doenc¸a sintéticos (DMARD)
 corticosteroides e/ou AINE e 3) qualquer tratamento
gicos.
ativos de depressão elevada: tratamento com DMARD
osteroides e/ou AINE, pagamento particular de fisioter-
 táxi, terapias alternativas e status ocupacional. A
 pessoa, o tratamento suplementar com cálcio e as
reditores de fadiga elevada. A idade acima de 65 anos
a elevada. A ansiedade foi um preditor independente
iedade elevada foram: gastroprotec¸ão com inibidores
paciente.
micos de níveis elevados de depressão, ansiedade ou
 para cada um dos desfechos mencionados; quando
 para a AR, esses preditores socioeconômicos explicam
da. A ansiedade, associada às variáveis socioeconômi-
 um importante preditor da fadiga em pacientes com
tda. Estee´ um artigo Open Access sob uma licenc¸a CC
 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
 therapy, non-steroidal anti-inflammatory drugs
ould be included, together with corticosteroids if
 order to control the pain and the inflammation
e RA patient’s general health condition. During the
tion of the above mentioned therapy, it is neces-
tect the digestive tract bleeding with proton-pump
(PPI), especially in patients with high gastroin-
eding risk. In addition, regular hematological and
l laboratory results follow ups are needed in order
a possible marrow bone damage and hepatotoxicity
DMARDs administration.4,5
is a subjective symptom that appears within the
 of diseases including the RA. Even though the
al consensus about the definition of the fatigue still
 achieved, a big number of authors define it as: “an
ing, sustained sense of exhaustion and decreased
Please cite tor in
in rheuma
ARTICLE IN PRESSRBRE-361; No. of Pages 11
r e v b r a s r e u m a t o l . 2 0 1 7;x x x(x x):xxx–xxx 3
capacity for physical and mental work”.6 The RA patients
define their fatigue as persistent, multidimensional symptom
with severe
as a sympt
a non-refre
high fatigu
symptoms,
psychosoci
is related to
apy compli
common de
However, th
mon influe
therapy an
and fatigue
Study goa
The primar
of the basic
apy, the de
RA complic
sion and fa
to evaluate
fatigue and
Methodo
Study locat
The study
April–Augu
bian prima
institution 
bia, Belgra
institutions
Sad, Serbia
Study desig
A multicen
ulation of o
was made 
categories 
absence/pr
Patients an
The patien
18 years w
from the st
depression
During 
survey that
First sectio
socioecono
referred to 
the curren
plications. In the third section there were three measuring
instruments of self-reported health condition of the patient:
e A
 Que
nxiet
ima
les in
sulti
nd G
 as a
10,1
 of P
n the
f the
 the
endin
days
ay).
sion
te th
estio
ith fi
ver; 2
sulti
imar
e fati
en v
sarco
 exa
age, 
emp
’s as
aym
er di
erve
ed tr
rren
ing o
erap
nist 
men
 hyal
lcium
ch or
ed 
l as 
t RA
IDs
DMA
 and
Ds. T
 RA 
s).
ical d
 the d
e Ko
 this article in press as: Lapcˇevic´ M, et al. Socioeconomic and therapy fac
, long term consequences to their daily life7–9 or
om that disrupts their daily activities and causes
shing sleep.10 Several studies have shown that the
e in RA patients was related to the pain, depression
 sleep disorder, high physical effort, gender and
al factors.11,12 Other reports found that depression
 the pain, fatigue, inability to work and lower ther-
ance.13,14 Some studies report a high incidence of a
pression and anxiety appearance in RA patients.15
ere is a lack of reports in the literature about com-
nces of the basic, adjuvant and supplemental RA
d socioeconomic factors to the anxiety, depression
 in RA patients.
ls
y goal of the study was to evaluate the influence
 RA therapy, the adjuvant and supplemental ther-
mographic and socioeconomic characteristics, the
ations and comorbidities to the anxiety, depres-
tigue in RA patients. The secondary objective was
 the relationship between the depression and the
 anxiety of RA patients.
logy
ion and time period
 was conducted during the time period from
st 2014 and included the RA patients from 20 Ser-
ry healthcare institutions, one tertiary healthcare
– Institute of Rheumatology, Clinical Centre of Ser-
de, Serbia, and also two specialized health spa
 – Nisˇka Banja, Nisˇ, Serbia and Jodna Banja, Novi
.
n
ter epidemiologic cross-sectional study in the pop-
lder RA patients was conducted. The cross section
according to the obtained self-reported outcome
of high fatigue absence/presence, high depression
esence and high anxiety absence/presence.
d procedures
ts of both genders suffering from RA older than
ere included. The criterion for excluding patients
udy was at least one missing answer in the fatigue,
 or anxiety questionnaires.
one visit to the doctor the patients filled in the
 contained questions grouped into three sections.
n contained questions related to demographic and
mic characteristics of the patients. The second one
the duration of the disease, type and duration of
t RA therapy, as well as the RA treatment com-
“Fatigu
Health
ized A
approx
Variab
The re
score a
sidered
score ≥
values
contai
ence o
during
by asc
– few 
every d
depres
evalua
ten qu
tions w
(1 – ne
The re
was pr
itor th
also be
in the 
The
were: 
tions, 
person
apist p
of oth
cal int
includ
tus, cu
beginn
rent th
antago
supple
sulfat,
and ca
stoma
perform
as wel
curren
(1) NSA
thetic 
NSAID
DMAR
of the
(month
Statist
Before
able th
toid arthritis patients. Rev Bras Reumatol. 2017. http://dx.doi.org/10.1016/j.r
fluence on self-reported fatigue, anxiety and depression
ssessment Scale” (FAS) with 10 items; “Patient
stionnaire” (PHQ-9) with 9 items, and “General-
y Disorder” (GAD-7) with 7 items. Patients needed
tely 30 min to fill out all the questionnaires.
 the study
ng variables in the study were PHQ-9 score, FAS
AD-7 score. The values of FAS score ≥22 were con-
 high fatigue.16 High anxiety was defined as GAD-7
7,18 while the high depression was defined by the
HQ-9 score ≥10.19 The GAD-7 and PHQ-9 surveys
 questions with provided answers about the pres-
 problem that caused dificulties to the patients
 previous two weeks, and which were numbered
g Likert ordinal scale from 0 to 3 (0 – not at all; 1
; 2 – more than a half of the time and 3 – almost
 The PHQ-9 survey is used to evaluate the level of
,20,21 while the GAD-7 was primarly developed to
e generalized anxiety disorder.17 The FAS contains
ns that describe the presence of possible condi-
ve provided ordinal answer modalities from 1 to 5
 – sometimes; 3 – ordinarily; 4 – often; 5 – always).
ng FAS score ranges from 10 to 50. The FAS survey
ly designed as an instrument to evaluate and mon-
gue in the general patient population,22 and it has
alidated as a reliable masuring fatigue instrument
idosis patients.23
mined demographic and socioeconomic variables
gender, marriage status, professional qualifica-
loyment status, occupation, the need for another
sistance, the need for frequent taxi use, physioter-
ent, assisitance device use due to RA, the presence
seases, osteoporosis presence, orthopedic surgi-
ntion and fractured limbs caused by the RA. The
eatment predictors were: current RA therapy sta-
t RA therapy duration (months), period from the
f the first RA symptoms until the start of the cur-
y (months), proton-pump inhibitor and H2 receptor
use in order to protect the stomach, the use of
ts that contain glucosamine sulfat, chondroitin
uronic acid, antirheumatic cream use, vitamin D3
 consummation, self-initiative therapy cessation,
 duodenum bleeding during RA therapy, surgery
because of the stomach or duodenum bleeding,
the use of alternative ways of treatments. The
 therapy is defined by three modalities such as:
 and/or analgesics and/or corticosteroids; (2) syn-
RDs alone or combined with corticosteroids and/or
 (3) any RA treatment which includes biologic
here were also data recorded about the duration
(months) as well as disease symptoms duration
ata processing
ata description, for each continous numerical vari-
lmogorov–Smirnov’s approval test of data set with
bre.2017.02.004
Please cite tor influence on self-reported fatigue, anxiety and depression
in rheuma
ARTICLE IN PRESSRBRE-361; No. of Pages 11
4 r e v b r a s r e u m a t o l . 2 0 1 7;x x x(x x):xxx–xxx
normal distribution was performed. In the data with a nor-
mal distribution, the continous variables are described by a
mean andate from no
an interqu
by frequen
categories.
relation of
monitored 
high fatigu
or Carmer’s
the contino
presence a
reported ou
risk factor a
done by the
of the relat
fatigue and
ear regressi
between th
done by the
the varianc
in the exist
index less 
level of sign
ducted usin
by the inst
patients’ co
Results
Out of 494 
study criter
years. The
interquarti
toms durat
RA was 159
to 240 mon
was 60 mo
months. T
ning of the
therapies s
from 24 to
NSAIDs an
months; in
the therap
tion with co
interquarti
ment whic
interquarti
of the FAS s
score was 1
Descript
is presente
variables w
One hun
PHQ-9 scor
≥22, while 
descriptive
Table 1 – Description of demographic and socioeconomic
variables in study population of patients with
mato
les 
r
ale 
e 
ation
rker 46 (11.3)
er 5 (1.2)
sewife 53 (13.0)
cial 41 (11.7)
sioner 227 (53.7)
mployed 37 (9.0)
l education level
hout school 7 (1.6)
entary school 89 (21.9)
ondary school 146 (35.8)
lege 98 (23.9)
ulty 69 (16.8)
al status
ried 274 (67.0)
arried 32 (7.9)
orced 28 (6.9)
ow/widower 67 (16.4)
ramarital communities 8 (1.8)
yment status
ployed – able to work 82 (20.1)
ployed – disable due to RA 13 (3.2)
mployed – working capable 61 (15.0)
mployed – disable due to RA 26 (6.3)
ired 227 (55.4)
f another person’s assistance
 178 (43.5)
231 (56.5)
nt taxi use
182 (44.6)
227 (55.4)
ayment of physiotherapist
 106 (25.9)
303 (74.1)
e of assistive devices
 96 (23.5)
313 (76.5)
diseases
hout other diseases 174 (42.5)
h other rheumatic disease 22 (5.5)
h other non-rheumatic disease 213 (52.0)
orosis
 139 (34.0)
270 (66.0)
pedic surgery for RA
 105 (25.7)
304 (74.3)
res due to RA
 65 (15.8)
344 (84.2)
eumatoid arthritis; f, frequency.
on, current therapy and the period from the beginning
symptoms until the current RA therapy start with the
f difference significance between the groups of patients
e absence and the group of patients with the presence
 depression, anxiety and the high fatigue are presented
le 3.
 this article in press as: Lapcˇevic´ M, et al. Socioeconomic and therapy fac
a standard deviation, while the data that devi-
rmal distribiution are described by a median and
artile range. The nominal variables are descibed
cy and percentage according to the appropriate
 In the methods of inferential statistics, the cor-
 individual category predictors with each of the
self-reported outcomes (absence/presence of the
e, anxiety or depression level) was evaluated by Phi
 V correlation coefficient. Difference evaluation in
us numerical variables between the group with the
nd the group with the absence of the tested self-
tcomes, was done by Mann–Whitney method. The
nalysis for each of the self-reported outcomes was
 binary logistic regression method. The assessment
ionship between the level of depression with the
 anxiety levels was performed by the multiple lin-
on (stepwise method). The diagnosis of collinearity
e predictors in the linear regression model was
 arbitrary assesment of the conditional index and
e inflation factor (VIF).24,25 The absence of a doubt
ance of the collinearity was defined by a conditional
than 15 and VIF value less than 3. The accepted
ificance was 0.05. The statistical analysis was con-
g IBM SPSS Statistics 20. This study was approved
itution’s institutional review board and obtained
nsent.
patients, 409 of them have fulfilled the inclusion
ia. The mean age of the patients was 58.03 ± 12.16
 RA duration median was 144 months with the
le range from 84 to 288 months, while the symp-
ion median (pain, limited mobility) caused by the
.5 months with the interquartile range from 107
ths. Duration median of the current RA therapy
nths with the interquartile range from 24 to 108
he median of the time passed from the begin-
 symptoms caused by the RA until all current RA
tart was 68.5 months with the interquartile range
 164 months, namely: (1) until the therapy with
d/or analgesics and/or corticosteroids (median = 48
terquartile range from 13 to 201 months); (2) until
y with synthetic DMARDs alone or in combina-
rticosteroids and/or NSAIDs (median = 49 months;
le range from 12 to 151 months); (3) any RA treat-
h includes biologic DMARDs (median = 99 months;
le range from 46 to 166 months). The average value
core was 27.31 ± 8.81. The mean value of the PHQ-9
0.13 ± 7.00 and of the GAD-7 score was 8.21 ± 6.11.
ion of demographic and socioeconomic variables
d in Table 1. In Table 2 the categories of the therapy
ere described.
dred and ninety seven (48.14%) patients had the
e ≥10. The same number also had the FAS score
148 (36.19%) patients had the GAD-7 score ≥10. The
 statistics for the duration of the disease, difficulties
rheu
Variab
Gende
Fem
Mal
Occup
Wo
Farm
Hou
Offi
Pen
Une
Forma
Wit
Elem
Sec
Col
Fac
Mariti
Mar
Unm
Div
Wid
Ext
Emplo
Em
Em
Une
Une
Ret
Need o
Yes
No 
Freque
Yes
No 
Self-p
Yes
No 
The us
Yes
No 
Other 
Wit
Wit
Wit
Osteop
Yes
No 
Ortho
Yes
No 
Fractu
Yes
No 
RA, rh
durati
of the 
level o
with th
of high
in Tab
toid arthritis patients. Rev Bras Reumatol. 2017. http://dx.doi.org/10.1016/j.r
id arthritis (n = 409).
f (%)
356 (87.0)
53 (13.0)
bre.2017.02.004
Please cite
in rheuma
ARTICLE IN PRESSRBRE-361; No. of Pages 11
r e v b r a s r e u m a t o l . 2 0 1 7;x x x(x x):xxx–xxx 5
Table 2 – Therapy variables description in study population of patients with rheumatoid arthritis (n = 409).
Variables 
The current
NSAIDs a
Synthetic 
Any RA t
Proton-pum
Yes
No 
Histamine H
Yes 
No 
Supplement
Yes 
No 
Antirheuma
Yes 
No 
Vitamin D3
Yes 
No 
Calcium sup
Yes 
No 
Patients disc
Yes 
No 
Bleeding fro
Yes 
No 
Operations d
Yes 
No 
Use of altern
Yes 
No 
RA, rheum
It was e
the GAD-7 
correlate w
comorbidit
pedic inter
category va
ture. Also, 
and the GA
most of th
discontinua
apy use (Ta
score have 
mine D3 t
with the an
gastrointes
category va
tion with th
therapy.
By the lo
the high de
tors (Table 
was the sy
the cortico
 RA therapy
nd/or analgesics and/or corticosteroids 
 DMARDs alone or in combination with corticosteroids and/or NSAIDs
reatment which includes biologic DMARDs 
p inhibitors
2 receptor antagonist
 of glucosamine sulphate, chondroitin sulphate, hyaluronic acid
tic creams
plements
ontinuation of RA therapy
 this article in press as: Lapcˇevic´ M, et al. Socioeconomic and therapy factor in
toid arthritis patients. Rev Bras Reumatol. 2017. http://dx.doi.org/10.1016/j.r
m the stomach or duodenum or the appearance of “black stool” during RA therapy
ue to bleeding from the stomach or duodenum or the appearance of “black stools”
ative methods of RA treatment
atoid arthritis; NSAIDs, non-steroidal anti-inflammatory drugs; DMARDs, di
stimated that the PHQ-9 score, the FAS score and
score category variables statistically significantly
ith the majority of socioeconomic variables and
y, except for gender, marital status and ortho-
vention (Table 4). In addition, the GAD-7 score
riable has not shown a correlation with bone frac-
it was noticed that the PHQ-9 score, the FAS score
D score statistically significantly correlate with
e therapy variables, except for the self-initiative
tion of the RA therapy and the alternative ther-
ble 5). Aditionally, the PHQ-9 score and the FAS
not shown a significant correlation with the vita-
herapy, while the FAS score has not correlated
tirheumatic cream use and with the operation in
tinal tract caused by bleeding. The GAD-7 score
riable also has not shown a significant correla-
e antirheumatic cream use, as well as the calcium
gistic regression model it was demonstrated that
pression was related to fiveindependent predic-
6). The significant predictor of the high depression
nthetic DMARDs therapy alone or combined with
steroids and/or NSAIDs. The sociodemographic
predictors 
self-payme
employmen
tus have sh
≥10. Those
work, and 
due to the R
the total va
so the vari
explained b
high depres
The log
fatigue was
The signific
another pe
mental the
age above 
ance od th
was indepe
model expl
variable. T
by 90.2%, w
explained w
f (%)
51 (12.5)
198 (48.4)
160 (39.1)
273 (66.8)
136 (33.2)
117 (28.5)
292 (71.5)
56 (13.6)
353 (86.4)
239 (58.5)
170 (41.5)
279 (68.2)
130 (31.8)
175 (42.9)
234 (57.1)
75 (18.4)
334 (81.6)
fluence on self-reported fatigue, anxiety and depression
bre.2017.02.004
45 (10.9)
364 (89.1)
18 (4.4)
391 (95.6)
52 (12.7)
357 (87.3)
sease-modifying antirheumatic drugs; f, frequency.
of the PHQ-9 score ≥10 were physiotherapist
nt, frequent taxi use, alternative treatment and
t status. Two categories of the employment sta-
own to be significant predictors of the PHQ-9 score
 are the category of unemployed but capable to
the category of unemployed as a disabled person
A. Thanks to the mentioned predictors the 70.2% of
riability of the dependent variable was explained,
ability of the presence of the high depression is
y 75.5%, while the variability of the absence of the
sion is explained by 65.3%.
istic regression model has shown that the high
 related to five independent predictors (Table 6).
ant predictors of the high fatigue were the need for
rson’s assistance and the calcium use as a suple-
rapy as well as the professional qualifications. The
65 years had a protective result on the appear-
e high fatigue. The GAD-7 score as a covariate
ndent predictor of the high fatigue. This logistic
ained the 84.4% of total variability of the dependent
he high fatigue presence variability is explained
hile the absence of the high fatigue variability is
ith 68.2%.
Please cite
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Table 3 – Descriptive statistics for the duration of the disease and symptoms and current therapy duration from the
appearance of symptoms to the start of current therapy of rheumatoid arthritis according to the absence/presence of
high depr f pat
Variables
The durati
e 
ce 
RA duratio
e 
ce 
The period
to the start
e
ce
Duration o
e 
ce 
The durati
e
ce
RA duratio
e 
ce 
The period
to the start
e 
ce 
Duration o
e 
ce 
The durati
ce 
RA duratio
The period
to the start
Duration o
PHQ-9, Pat
The sign
regression 
tection an
pensioner 
total pensi
the presen
while the 
anxiety wa
The line
nificant co
the FAS sc
9 score = −
multiple lin
were: (1) fo
7 score (t =
p = 0.000). T
linear mod
change of 
with the FA
in comparis
(F changes 
model that
of the PHQ
ession, high fatigue and high anxiety in study population o
Outcome 
on of the current RA therapy (months)
PHQ ≥ 10 absenc
PHQ ≥ 10 presen
n (months)
PHQ ≥ 10 absenc
PHQ ≥ 10 presen
 from the first appearance of RA symptoms
 of the current RA therapy (months)
PHQ ≥ 10 absenc
PHQ ≥ 10 presen
f symptoms due to RA (months)
PHQ ≥ 10 absenc
PHQ ≥ 10 presen
on of the current RA therapy (months)
FAS ≥ 22 absenc
FAS ≥ 22 presen
n (months)
FAS ≥ 22 absenc
FAS ≥ 22 presen
 from the first appearance of RA symptoms
 of the current RA therapy (months)
FAS ≥ 22 absenc
FAS ≥ 22 presen
f symptoms due to RA (months)
FAS ≥ 22 absenc
FAS ≥ 22 presen
on of the current RA therapy (months)
GAD ≥ 10 absen
 this article in press as: Lapcˇevic´ M, et al. Socioeconomic and therapy factor in
toid arthritis patients. Rev Bras Reumatol. 2017. http://dx.doi.org/10.1016/j.r
GAD ≥ 10 presence 
n (months)
GAD ≥ 10 absence 
GAD ≥ 10 presence 
 from the first appearance of RA symptoms
 of the current RA therapy (months)
GAD ≥ 10 absence 
GAD ≥ 10 presence 
f symptoms due to RA (months)
GAD ≥ 10 absence 
GAD ≥ 10 presence 
ient Health Questionnaire; FAS, Fatigue Assessment Scale; GAD-7, Generaliz
ificant predictor of the high anxiety in the logistic
model were proton pump inhibitor gastropro-
d two occupation categories – housewife and
(Table 6) and these predictors explained 64.8% of
oner of the dependent variable. The variability of
ce of the high anxiety was explained with 13.5%,
explained pensioner of absence of the severe
s 93.9%.
ar regression model resulted in the statistically sig-
rrelation of the PHQ-9 score with the GAD-7 and
ores. That was presented by the equation: PHQ-
3.47 + 0.634 × GAD-7 score + 0.323 × FAS score. The
ear regression model statistics for the predictors
r the constant (t = −0.784; p = 0.000); (2) for the GAD-
 0.548; p = 0.000) and (3) for the FAS score (t = 0.402;
he determination coefficient (R2) for the mentioned
el was 0.788. There was a statistically significant
the R2 for the mentioned linear regression model
S score and GAD-7 score predictors for PHQ-9 score
son with model that contains only the GAD-7 score
= 124.979; df1 = 1; df2 = 408; p = 0.000). The R2 of the
 contained the GAD-7 score, as the only predictor
-9 was 0.716. The biggest conditional index in the
linear regre
VIF values 
Discussio
According 
sion, the lo
social confl
son, and al
factors or b
sion and s
interperson
tors that ca
inflammati
erbation an
results hav
due to a dis
nificant pre
of the high
(Table 6). T
defines a ba
ment), also
ients with rheumatoid arthritis.
Percentiles p
25 50 75
18.00 53.00 84.00
0.001
36.00 72.00 120.00
84.00 120.00 204.00
0.008
96.00 168.00 240.00
25.50 66.00 151.50
0.645
24.00 73.00 183.50
90.00 145.00 221.00
0.006
112.50 180.00 263.50
18.00 48.00 77.00
0.000
24.50 61.50 120.00
84.00 120.00 186.00
0.012
96.00 156.00 240.00
27.00 60.00 144.00
0.749
24.00 73.00 181.00
88.00 144.00 210.00
0.013
108.00 177.00 263.50
20.00 60.00 84.00
fluence on self-reported fatigue, anxiety and depression
bre.2017.02.004
0.002
36.00 72.00 120.00
84.00 144.00 204.00
0.015
96.00 168.00 240.00
25.00 72.00 161.00
0.018
24.00 66.00 189.00
93.00 152.00 228.00
0.790
122.00 180.00 274.50
ed Anxiety Disorder; RA, rheumatoid arhtritis.
ssion model with two predictors was 10.021. The
in both predictors were identical and were 2.221.
n
to the social signal transduction theory of depres-
w socioeconomic status implies the high risk of
icts, social isolation, excluding or rejecting a per-
so represents one of the most important provoking
ig stressful life events that cause the major depres-
timulation of inflammation.26 In RA patients the
al loss and the social isolation are the key fac-
n lead to the disease exacerbation caused by the
on or to the additional depression symptoms exac-
d the appearance of the major depression.27 Our
e shown that the experience of the unemployement
ability in RA patients, among all other resulting sig-
dictors, represents the strongest provoking factor
 depression that includes the major depression too
his RA patient’s experience, besides that it clearly
d socioeconomic status of the patient (unemploy-
 has a strong component of the experience of the
Please cite this article in press as: Lapcˇevic´ M, et al. Socioeconomic and therapy factor influence on self-reported fatigue, anxiety and depression
in rheumatoid arthritis patients. Rev Bras Reumatol. 2017. http://dx.doi.org/10.1016/j.rbre.2017.02.004
ARTICLE IN PRESSRBRE-361; No. of Pages 11
r e v b r a s r e u m a t o l . 2 0 1 7;x x x(x x):xxx–xxx 7
Table 4 – Correlations between categories of demographic and socioeconomic variables and variables of comorbidity
with absence/presence of high depression, fatigue and anxiety in patientswith rheumatoid arthritis.
Variables PHQ-9 score ≥10
Correlation (p)
FAS score ≥22
Correlation (p)
GAD-7 score ≥10
Correlation (p)
Absence
n1 = 212
Presence
n2 = 197
Absence
n1 = 212
Presence
n2 = 197
Absence
n1 = 212
Presence
n2 = 197
Gender
Female −0.082 (0.101) −0.072 (0.136) −0.067 (0.165)
Male
Occupation
Worker
Farmer
Housewife
Official 0.341a (0.000) 0.273a (0.000) 0.229a (0.000)
Pensioner
Unemployed
Formal education level
Without school
Elementary school
Secondary school 0.329a (0.000) 0.323a (0.000) 0.259a (0.000)
College
Faculty
Maritial status
Married
Unmarried
Divorced 0.130 (0.148) 0.138 (0.083) 0.141 (0.077)
Widow/widower
Extramarital communities
Employment status
Employed – able to work
Employed – disable due to RA
Unemployed – working capable 0.302a (0.000) 0.267a (0.000) 0.209a (0.003)
Unemployed – disable due to RA
Retired
Need of another person’s assistance
Yes −0.368a (0.000) −0.369a (0.000) −0.271a (0.000)
No
Frequent taxi use
Yes −0.346a (0.000) −0.282a (0.000) −0.246a (0.000)
No
Self-payment of physiotherapist
Yes −0.312a (0.000) −0.224a (0.000) −0.229a (0.000)
No
The use of assistive devices
Yes −0.290a (0.000) −0.199a (0.000) −0.186a (0.000)
No
Other diseases
Without other diseases
With other rheumatic disease 0.190a (0.001) 0.214a (0.000) 0.152a (0.007)
With other non-rheumatic disease
Osteoporosis
Yes −.173a (0.001) −0.156a (0.002) −0.182a (0.000)
No
Orthopedic surgery for RA
Yes 0.117 (0.083) 0.049 (0.632) 0.113 (0.088)
No
Fractures due to RA
Yes −0.110b (0.031) −0.134a (0.007) −0.078 (0.116)
No
PHQ-9, Patient Health Questionnaire; FAS, Fatigue Assessment Scale; GAD-7, Generalized Anxiety Disorder; RA, rheumatoid arthritis.
a Level of statistical significance for p ≤ 0.01.
b Level of statistical significance for p ≤ 0.05.
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Table 5 – Correlations between categories of therapy with absence/presence of high depression, fatigue and anxiety in
patients with rheumatoid arthritis.
Variable
nt
97
The current
NSAIDs a
Syntheti
corticost
Any RA t
Proton-pum
Yes 
No
Histamine H
Yes 
No
Supplement
Yes 
No
Antirheuma
Yes 
No
Vitamin D3
Yes
No
Calcium sup
Yes 
No
Patients dis
Yes 
No
Bleeding fro
Yes 
No
Operations 
Yes 
No
Use of altern
Yes 
No
PHQ-9, Pat
non-steroid
a Level of s
b Level of s
social rejec
disability. O
mic status 
PHQ-9 surv
the depress
pability of 
socioecono
sioner statu
frequent ta
payment of
also imply 
lack of the
as their add
have on the
of physioth
or some ot
PHQ-9 score ≥10
Correlation (p)
Absent
n1 = 212
Prese
n2 = 1
 RA therapy
nd/or analgesics and/or corticosteroids
c DMARDs alone or in combination with
eroids and/or NSAIDs
0.228a (0.000)
reatment which includes biologic DMARDs
p inhibitors
−0.137a (0.007) 
2 receptor antagonist
−0.157b (0.011) 
 of glucosamine sulphate, chondroitin sulphate, hyaluronic acid
 this article in press as: Lapcˇevic´ M, et al. Socioeconomic and therapy factor in
toid arthritis patients. Rev Bras Reumatol. 2017. http://dx.doi.org/10.1016/j.r
0.161a (0.008) 
tic creams
−0.191a (0.000) 
0.023 (0.644)
plements
−0.140a (0.004) 
continuation of RA therapy
−0.065 (0.230) 
m the stomach or duodenum or the appearance of “black stool” during RA therapy
−0.243a (0.000) 
due to bleeding from the stomach or duodenum or the appearance of “black stools”
−0.154a (0.003) 
ative methods of RA treatment
0.079 (0.122) 
ient Health Questionnaire; FAS, Fatigue Assessment Scale; GAD-7, Generaliz
al anti-inflammatory drugs; DMARDs, disease-modifying antirheumatic dr
tatistical significance for p ≤ 0.01.
tatistical significance for p ≤ 0.05.
tion, isolation and interpersonal loss due to the
ther authors also found that the bad socioecono-
increases the depression symptoms measured by
ey in RA patients.28 Löwe et al. demonstrated that
ion is a significant predictor of the working inca-
the RA patients.29 In our study, other significant
mic predictors of the high depression were: pen-
s, unemployment of the working capable patients,
xi use, self-payment of physiotherapist and self-
 alternative treatment. The last mentioned factors
a bad socioeconomic RA patients’ status due to the
 income or insufficient personal income, as well
itional financial exhaustion by the expenses they
ir own during the daily activities, implementation
erapy measurements or the alternative treatment
her activities required at the rehabilitaion, pain
relief and t
eral.
We also
influence o
patients, b
DMARD the
roids or/an
aforementi
have a high
RA activity
longitudina
toms predic
increased R
socioecono
baseline, M
and/or biol
FAS score ≥22
Correlation (p)
GAD-7 score ≥10
Correlation (p)
Absent
n1 = 254
Present
n2 = 155
Absent
n1 = 212
Present
n2 = 197
0.223a (0.000) 0.193a (0.000)
−0.145a (0.003) −0.116b (0.019)
−0.131b (0.037) −0.165a (0.005)
fluence on self-reported fatigue, anxiety and depression
bre.2017.02.004
0.111 (0.090) 0.122 (0.055)
0.131b (0.027) 0.137b (0.021)
0.031 (0.523) −0.104b (0.039)
−0.110b (0.025) −0.065 (0.230)
−0.045 (0.395) −0.082 (0.116)
0.120b (0.014) 0.139a (0.005)
−0.057 (0.246) −0.113b (0.024)
−0.055 (0.271) 0.043 (0.385)
ed Anxiety Disorder; RA, rheumatoid arthritis; NSAIDs,
ugs.
he improvement of the social functioning in gen-
 showed that, in general, the RA therapy has no
n the appearance of the high depression in RA
ut there is a significant influence of the synthetic
rapy category alone or combined with corticoste-
d NSAID. In our study population patients with the
oned treatment modality were 80% more likely to
 depression, which potentially indicates a higher
 in these patients. It was demonstrated in some
l studies that persistent depression/anxiety symp-
t poor treatment response which corresponds with
A activity over time.30 In a univariate analysis of
mic and clinical characteristics of the RA patients
argaretten et al. demonstrated that synthetic
ogic DMARDs therapy increases major depression
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r e v b r a s r e u m a t o l . 2 0 1 7;x x x(x x):xxx–xxx 9
Table 6 – Logistic regression models parameters according to sociodemographic, socioeconomic and therapeutic
predictors of high depression, fatigue and anxiety in patients with rheumatoid arthritis.
Predictors Wa
Examined 
The curre 4
NSAID 0
Synthe
cortico
4
Self-paym 12
Employme 18
Employ
Unemp 9
Unemp 7
Retired 15
Frequent 8
Use of alt 4
Constant 31
Examined 
Need of a
GAD-7 sc
Calcium s
Age > 65 g
Formal ed
Withou
Elemen
Second
College
Constant 
Examined 
Occupatio
Farmer
Housew
Officia
Pensio
Unemp
Proton-pu
Constant 
PHQ-9, Pati
non-steroid
frequency.3
apy influen
in the RA p
the current
of Republic
are human
effects of tu
mentioned
scribed to 
active (i.e. 
the implem
week) or de
thetic DMA
showed tha
biologic DM
to the other
one or two
can be inte
B SE 
outcome – PHQ-9 score ≥ 10
nt RA therapy 
s and/or analgesics and/or corticosteroids 0.324 0.447 
tic DMARDs alone or in combination with
steroids and/or NSAIDs
0.630 0.283 
ent of physiotherapist 1.250 0.349 
nt status
ed – disable due to RA 0.404 0.864 
loyed – working capable 1.357 0.435 
loyed – disable due to RA 1.900 0.697 
1.384 0.354 
taxi use 0.785 0.275 
ernative methods of RA treatment 0.772 0.385 
−2.756 0.493 
outcome – FAS score ≥ 22
 this article in press as: Lapcˇevic´ M, et al. Socioeconomic and therapy factor in
toid arthritis patients. Rev Bras Reumatol. 2017. http://dx.doi.org/10.1016/j.rnother person’s assistance 1.102 0.384 8
ore 0.320 0.048 43
upplements 0.855 0.357 5
odina −1.031 0.478 4
ucation level 13
t school 17.112 18,629.741 0
tary school 0.270 0.530 0
ary school 1.589 0.452 12
 0.693 0.474 2
−1.532 0.586 6
outcome – GAD score ≥ 10
n 17
−0.024 1.207 0
ife 1.245 0.448 7
l −0.719 0.590 1
ner 0.837 0.370 5
loyed 0.675 0.489 1
mp inhibitors 0.491 0.238 4
−1.566 0.382 16
ent Health Questionnaire; FAS, Fatigue Assessment Scale; GAD-7, Generaliz
al anti-inflammatory drugs; DMARDs, disease-modifying antirheumatic dr
1 However, in other reports there was no RA ther-
ce on the self-reported high depression frequency
atients.32 Both before and during the study period
 biologic drugs provided by the health insurance
 of Serbia, that were available to the RA patients
 protein drugs that neutralize pro-inflammatory
mor necrosis factor and interleukin-6. The above
 biologic drug combined with methotrexate is pre-
the RA patients whose disease is still clinically
whose Disease Activity Score is above 5.1) despite
entation of methotrexate (at least 15 mg once a
spite the implementation of the combined two syn-
RDs during at least three months. Also, our results
t median of RA patients time of “expectation” of
ARDs therapy was almost twice longer compared
 modalities of therapy. So, the RA patient that uses
 synthetic DMARDs can have an experience that
rpreted as: “my health condition caused by RA is a
long time s
treat a canc
no hope for
biologic dru
rience of d
one of the c
of major de
We also
increase th
that the hi
one from a
depression
that the in
risk of the
facts since
fatigue. Wi
specific m
with antide
ld df p Odds ratio 95.0% Confidence
interval
Lower Upper
.982 2 0.083
.525 1 0.469 1.383 0.575 3.323
.972 1 0.026 1.878 1.079 3.269
.841 1 0.000 3.490 1.762 6.914
.117 4 0.001
.218 1 0.640 1.498 0.275 8.151
.731 1 0.002 3.884 1.656 9.111
.423 1 0.006 6.687 1.704 26.238
.252 1 0.000 3.989 1.992 7.989
.179 1 0.004 2.193 1.280 3.755
.024 1 0.045 2.164 1.018 4.600
.274 1 0.000 0.064
fluence on self-reported fatigue, anxiety and depression
bre.2017.02.004
.220 1 0.004 3.009 1.417 6.389
.986 1 0.000 1.377 1.253 1.514
.738 1 0.017 2.352 1.168 4.736
.653 1 0.031 0.357 0.140 0.910
.994 4 0.007
.000 1 0.999 27,004.818 0.000
.259 1 0.611 1.310 0.463 3.702
.389 1 0.000 4.901 2.023 11.876
.142 1 0.143 2.000 0.790 5.062
.837 1 0.009 0.216
.908 5 0.003
.000 1 0.984 0.976 0.092 10.400
.717 1 0.005 3.474 1.443 8.366
.486 1 0.223 0.487 0.153 1.548
.121 1 0.024 2.309 1.119 4.766
.901 1 0.168 1.963 0.752 5.123
.248 1 0.039 1.634 1.024 2.608
.822 1 0.000 0.209
ed Anxiety Disorder; RA, rheumatoid arthritis; NSAIDs,
ugs.
erious. . . I know that one of the drugs that I use can
er too. . . I can’t understand that, even so, there is
 me. . . I am not worth to be given such an expensive
g.” Such an individual, longstanding patient expe-
isforia, hopelessness and uselessness, can also be
ontextual, psychosocial triggers for the appearence
pression and poor RA treatment response.
 found that the RA therapy (Table 6) does not
e risk of the high fatigue or depression, as well as
gh fatigue and anxiety, completely independent
nother, lead to the high level of the self-reported
 symptoms. On the other hand, the results imply
crease of the anxiety level also increases the
 high fatigue appearance. These are important
 there is no specific pharmacotherapy of the high
th all the above mentioned, we highlight that the
edicamentous therapy should be implemented
pressants that have a strong anxiolytic effect (for
Please cite tor in
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ARTICLE IN PRESSRBRE-361; No. of Pages 11
10 r e v b r a s r e u m a t o l . 2 0 1 7;x x x(x x):xxx–xxx
example with selective serotonin reuptake inhibitors), both in
order to re
decrease th
In our s
on the appe
of finding c
that, depen
has a non-
fatigue eva
of the ment
ever, the st
any change
We also
apy for pr
patients ca
appearance
ments the
adequate m
common sy
that about 
levels of se
with the h
mone secre
bone mine
From so
the high fat
ple’s help a
that is defin
education t
jon et al. fo
lasting less
pared to th
than 12 ye
implies som
performing
the restrict
fatigue, and
negatively 
When it
anxiety in 
were two c
(Table 6). It
with the m
their spous
the specific
spent in th
ily surroun
is inversely
understand
Addition
was also a
bia, unlike 
cheap, the 
therapy by 
fear wheth
PPI, for the
high RA pa
therapy pre
in spite of 
lation with
predictors share a small mutual variance of all three outcomes
ssion, fatigue and anxiety), which implies that they are
ecific
 lim
ign.
 spe
pear
ts, c
mato
 act
e ce
n th
ses. 
 RA a
 the 
houg
ale p
quen
ctors
es t
alyz
ed a
 anx
usio
raph
onte
pear
gh an
 the 
with
 the
gh an
mat
icts 
r Mir
t. Au
rest.
 con
e ha
es th
owl
 than
es of
enui
o th
 Ana
r e n
man
hritis
ery P
olen 
 this article in press as: Lapcˇevic´ M, et al. Socioeconomic and therapy fac
duce the depression symptoms and to potentially
e high fatigue of the RA patients.
tudy the age above 65 years had a protective effect
arance of the high fatigue in RA patients. This kind
oexists with the findings of Watt et al., who showed
ding on the age, fatigue in the general population
linear trend.33 In the general population a global
luation after the age of 65 was decreasing because
al and cognitive fatigue component decrease. How-
udies in the RA patients populations did not show
s in the fatigue level with the change of age.34
 demonstrated that calcium suplementation ther-
ophylaxis or therapy of osteoporosis in the RA
n significantly increase the risk of the high fatigue
. This potentially suggests that calcium supple-
rapy in our patients was administered without
onitoring of serum ionized calcium. Fatigue is very
mptom of hypercalcemia.35 Oelzner et al. reported
30% of the RA patients have hypercalcemia (high
rum ionized calcium) that occurs in association
igh disease activity, suppressed parathyroid hor-
tion, suppressed vitamin D hormone synthesis and
ral density reduction.36
cioeconomic factors the important predictors of
igue in the RA patients were the need for other peo-
nd care, as well as the level of the formal education
ed as finished college education. In Serbia formal
o obtain a college degree lasts for 12 years. Castre-
und that the RA patients with a formal education
 than or exactly 12 years had the bigger fatigue com-
e patients with formal education that lasted more
ars.37 The need for other people’s help and care
e severe setback and these RA patients’ problem in
 daily activities. In other studies it was shown that
ion of daily activities correlates positively with the
 that the increase of the daily activities correlates
with the fatigue.38,39
 comes to the socioeconomic predictors of the high
our study population, the significant risk factors
ategories of occupation – pensioner and housewife
 is described in the literature that the housewives
ilder RA were more anxious even though they had
e’s understanding for their disease.40 Patients with
 occupation categories whose social life is mostly
e house or mostly related to the house and fam-
dings can possibly experience more anxiety that
 related to the RA severity and the experienced
ing by the persons with whom they live.
ally, the risk factor of the high anxiety appearance
 stomach bleeding prevention by the PPI. In Ser-
the drugs from the H2 antagonist group which are
RA patients have to pay for the PPI gastroprotecive
themselvess which is very expensive for them. The
er and how long they will be able to pay for the
 gastroprotection can alsobe a risk factor of the
tients’ anxiety. The rest of the socioeconomic and
dictors in this study (Tables 4 and 5) have shown,
the achieved statistical significance, a weak corre-
 the self-reported outcomes of the patients. These
(depre
not sp
The
its des
ate the
the ap
patien
inflam
the RA
exclud
betwee
respon
and/or
tion of
Even t
the m
Conse
risk fa
outcom
less an
record
and/or
Concl
Demog
with c
the ap
and hi
tion of
along 
tion on
and hi
in rheu
Confl
Autho
interes
of inte
has no
that sh
declar
Ackn
We are
diseas
their g
are als
text to
r e f e 
1. Ala
art
2. Em
Sm
toid arthritis patients. Rev Bras Reumatol. 2017. http://dx.doi.org/10.1016/j.r
fluence on self-reported fatigue, anxiety and depression
 for any of them.
itations of our study primarily originate from
 A cross sectional study design does not evalu-
cifics of the questioned predictors’ influences on
ance of the fatigue, depression and anxety in RA
ompared to the patient population with another
ry or non-inflammatory disease. In our study,
ivity was not monitored and therefore we cannot
rtain bias in our explanations of the relationship
e appearance of the high depression and treatment
Since we have not monitored the status of calcemia
ctivity, there also may be some bias in our explana-
link between the high fatigue and calcium therapy.
h we had a large patients population in the study,
opulation response number was unusually small.
tly, compared to the female population, observed
 of the appearance of the questioned self-reported
hat come from the male population are potentially
ed. Also, in our RA patient population we haven’t
ny data about the use of antidepressant, sedative
iolytic drugs.
n
ic, socioeconomic and psychosocial factors, along
xtual and treatment factors, can largely explain
ance of the high level of depression and fatigue
xiety in rheumatoid arthritis patients. The evalua-
psychosocial, socioeconomic and therapy impacts,
 the rheumatoid arthritis activity and inflamma-
 appearance of the high depression, high fatigue
xiety can be of great importance in future studies
oid arthritis patients.
of interest
jana Lapcˇevic´ declares that she has no conflict of
thor Mira Vukovic´ declares that she has no conflict
 Author Branislav S. Gvozdenovic´ declares that he
flict of interest. Author Vesna Mioljevic´ declares
s no conflict of interest. Author Snezˇana Marjanovic´
at she has no conflict of interest.
edgements
kful to the Association of patients with rheumatic
 the Republic of Serbia (ORS), Belgrade, Serbia, for
ne engagement in the organization of this study. We
ankful for linguistic corrections of the manuscript
 Vukovic´, language and literature professor.
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bre.2017.02.004
	Socioeconomic and therapy factor influence on self-reported fatigue, anxiety and depression in rheumatoid arthritis patients
	Introduction
	Study goals
	Methodology
	Study location and time period
	Study design
	Patients and procedures
	Variables in the study
	Statistical data processing
	Results
	Discussion
	Conclusion
	Conflicts of interest
	Acknowledgements
	References