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Citation: Stroie, T.; Preda, C.; Meianu,
C.; Istr˘atescu, D.; Manuc, M.;
Croitoru, A.; Gheorghe, L.; Gheorghe,
C.; Diculescu, M. Fatigue Is
Associated with Anxiety and Lower
Health-Related Quality of Life in
Patients with Inflammatory Bowel
Disease in Remission. Medicina 2023,
59, 532. https://doi.org/10.3390/
medicina59030532
Academic Editor: Jan Bilski
Received: 22 January 2023
Revised: 4 March 2023
Accepted: 7 March 2023
Published: 9 March 2023
Copyright: © 2023 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
medicina
Article
Fatigue Is Associated with Anxiety and Lower Health-Related
Quality of Life in Patients with Inflammatory Bowel Disease
in Remission
Tudor Stroie 1,2 ,*, Carmen Preda 1,2, Corina Meianu 1,2, Doina Istrătescu 1,2, Mircea Manuc 1,2, Adina Croitoru 3,4 ,
Liana Gheorghe 1,2, Cristian Gheorghe 1,2 and Mircea Diculescu 1,2
1Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
2Gastroenterology Department, Fundeni Clinical Institute, 022328 Bucharest, Romania
3Faculty of Medicine, Titu Maiorescu University, 040441 Bucharest, Romania
4Oncology Department, Fundeni Clinical Institute, 022328 Bucharest, Romania
*Correspondence: tudor.stroie@drd.umfcd.ro
Abstract:
Background and Objectives: Inflammatory bowel diseases (IBD) are chronic conditions with
an unpredictable course and a remitting–relapsing evolution. Fatigue is a frequent complaint in
patients with IBD, affecting approximately half of the newly diagnosed patients with IBD. The
aim of this study was to analyze fatigue in patients with IBD in remission. Materials and Methods:
One hundred nineteen consecutive outpatients diagnosed with IBD for over 3 months that were in
corticosteroid-free clinical and biochemical remission at the time of assessment were included in
this cross-sectional study. Out of them, 72 (60.5%) were male; the median age was 39 years (IQR
30–47). Seventy-seven patients (64.7%) were diagnosed with Crohn’s disease and forty-two (35.3%)
with ulcerative colitis, with a median disease duration of 6 years (IQR 2–10). Fatigue, health-related
quality of life (HR-QoL), anxiety and depression were evaluated using the following self-administered
questionnaires: FACIT Fatigue, IBDQ 32 and HADS. Results: The mean FACIT-Fatigue score was
41.6 (SD
±
8.62), and 38.7% of patients were revealed as experiencing fatigue when a cut-off value
of 40 points was used. The mean IBDQ 32 score was 189.4 (SD
±
24.1). Symptoms of anxiety and
depression were detected in 37% and 21% of the patients, respectively. In the multivariate analysis,
fatigue was significantly associated with lower HR-QoL (OR 2.21, 95% CI: 1.42–3.44, p< 0.001),
symptoms of anxiety (OR 5.04, 95% CI: 1.20–21.22, p= 0.008), female sex (OR 3.32, 95% CI: 1.02–10.76,
p= 0.04) and longer disease duration (OR 1.13, 95% CI: 1.01–1.27, p= 0.04). Conclusions: Fatigue is
highly prevalent even in patients with inactive IBD and is correlated with lower HR-QoL and anxiety,
as well as with clinical factors such as longer disease duration and female sex.
Keywords: inflammatory bowel disease; fatigue; quality of life; anxiety; depression
1. Introduction
Inflammatory bowel diseases (IBD) with the two subtypes of Crohn’s disease (CD)
and ulcerative colitis (UC) represent chronic inflammatory diseases with an unpredictable
course, which leads to significant impairment in affected patients’ health-related quality of
life (HR-QoL) and high levels of fatigue [1,2].
Fatigue is defined as ‘a persistent, overwhelming sense of tiredness, weakness or
exhaustion resulting in a decreased capacity for physical and/or mental work’ [
3
,
4
]. It
is frequently encountered in chronic inflammatory diseases such as IBD, rheumatoid
arthritis, systemic lupus erythematosus or multiple sclerosis; in patients with IBD, fatigue
is a common complaint; approximately half of the newly diagnosed patients with IBD
experiencing fatigue: 42–47% of patients with UC and 48–62% of patients with CD [
5
,
6
].
Regarding the disease activity, the prevalence of fatigue in patients in remission ranges
between 41% and 48%; however, in patients with active disease it can be up to 86% [
3
].
Medicina 2023,59, 532. https://doi.org/10.3390/medicina59030532 https://www.mdpi.com/journal/medicina
Medicina 2023,59, 532 2 of 10
In addition, it is among the most frequent non-intestinal symptoms reported by patients,
being more burdensome than gastrointestinal symptoms such as diarrhea or bowel urgency
for the IBD patients [
7
,
8
]. There is also a strong association between fatigue and HR-QoL,
with patients with fatigue having a significantly lower HR-QoL and vice versa [9,10].
Patients with IBD deal with fatigue more often than healthy controls. Active dis-
ease, lower hemoglobin values and altered sleeping patterns are among the predictors of
fatigue [11].
The etiology of fatigue is multifactorial: chronic inflammatory state, anemia, micronu-
trients deficiencies due to malabsorption or accelerated intestinal transit, self-imposed
dietary restrictions, adverse effects of medication, psychological disturbances, intestinal
dysbiosis or dysregulations of the brain–gut axis may play important roles [6].
The management of fatigue in patients with IBD can be quite challenging because of
its complex etiology and the limited knowledge on the pathogenesis of IBD-related fatigue,
and requires a multidisciplinary approach. Kreijne et al. proposed a fatigue attention
cycle that consists of seven steps: screening, assessment of concurrent symptoms, thorough
fatigue evaluation, general anti-fatigue strategies, interventions and re-evaluation [
12
].
Patients with IBD, especially those with active disease, are prone to nutritional and mi-
cronutrient deficiencies which should be corrected. A review of the patient’s medication
should be performed, since fatigue can be a side effect of certain medications. Non-
pharmacological interventions, such as physical activity or psychosocial interventions may
be beneficial. Currently, there are no drugs available that could specifically target fatigue in
these patients [6,12].
Anxiety and depression are frequently encountered comorbidities in patients with
IBD. Up to 35.1% and 21.6% of patients with IBD have symptoms of anxiety and depression,
respectively [
13
]. They play an important role in determining fatigue, being among its
most important psychological predictive factors [
10
]. A study conducted by Norton et al.
assessed fatigue in patients with IBD using three different scales for measuring fatigue:
Multidimensional Fatigue Inventory (MFI), Inflammatory Bowel Disease Fatigue (
IBD-F
)
and Multidimensional Assessment of Fatigue (MAF). Even though in the univariate analysis
both anxiety and depression were predictive factors for fatigue, in the multivariate analysis
only depression along with lower QoL were consistently associated with fatigue on all
scales [
14
]. Similarly, a population-based Norwegian study showed that anxiety, depression
and poor sleep quality are associated with fatigue at 20 years after the diagnosis of IBD [
15
].
Conversely, both symptoms of anxiety and depression can manifest as fatigue, and it may
be difficult to distinguish them from IBD-associated fatigue [16].
The majority of studies available in the literature that assess fatigue in patients with
IBD are not specially focused on patients in remission. Moreover, studies that are designed
for patients in remission assess disease activity only on a clinical basis, without considering
biochemical markers of disease activity such as CRP and fecal calprotectin.
The aim of this study was to analyze fatigue in patients with IBD in both clinical and
biochemical remission and to identify factors associated with it.
2. Materials and Methods
2.1. Study Population and Design
This was a cross-sectional, observational study.
All patients included in this study were at least 18 years old and were in corticosteroid-
free clinical and biochemical remission for more than three months. Pregnant females,
patients being treated with corticosteroids, patients with ostomy, perianal disease, extrain-
testinal manifestations or other significant comorbidities or medical conditions that could
have influenced their level of fatigue or quality of life were excluded. Patients already
diagnosed with anxiety, depression or other psychiatric conditions were also excluded.
One hundred and forty-one consecutive outpatients diagnosed with IBD for over
3 months that fulfilled the eligibility criteria at the time of assessment were invited to
participate in the study. Out of them, 130 accepted and provided their consent to be
Medicina 2023,59, 532 3 of 10
included in this study. Eight patients had incomplete data and were excluded from the
analysis. Another three patients had proof of endoscopic activity and were not considered
eligible. Therefore, 119 patients were effectively enrolled in the study.
The patients were treated for IBD at Fundeni Clinical Institute, a tertiary gastroenterol-
ogy center in Bucharest, Romania. They were invited to participate in this study when they
had their routine follow-up visit or treatment administration visit in the outpatient clinic.
The enrollment took place between September 2022 and November 2022.
2.2. Questionnaires and Data Collection
The participants answered a series of auto-administered questionnaires evaluating
their level of fatigue, their HR-QoL and their experiences of anxiety and depression:
FACIT Fatigue, IBDQ 32 and HADS. Validated Romanian versions of these questionnaires
were used.
The Functional Assessment of Chronic Illness Therapy—Fatigue (FACIT-Fatigue) is
a unidimensional scale used to assess fatigue, validated in the general population and a
series of chronical conditions, including IBD. The total score ranges from 0 to 52 points,
with lower scores representing greater fatigue [17].
The Inflammatory Bowel Disease Questionnaire (IBDQ) is a 32-item questionnaire
developed by Guyatt et al. in 1989 used to assess the HR-QoL in patients with IBD. The
total score ranges from 0 to 224 points, with higher scores representing better HR-QoL [
18
].
Hospital Anxiety and Depression Scale (HADS) is a questionnaire used to assess
patients for clinically significant anxiety and depression. A total score over 7 points is
considered pathological for both anxiety and depression [19–22].
Fatigue was considered for FACIT-Fatigue score
≤
40. Symptoms of anxiety and/or
depression were considered to be present when patients had a HADS-A score > 7 and/or a
HADS-D score > 7, respectively.
Results from blood samples collected during the visit at the hospital were used in this
study. Male patients that had a hemoglobin level < 13 g/dL and female patients with a
hemoglobin level < 12 g/dL were considered to have anemia.
Data regarding the patients’ demographics, lifestyle and the characteristics of the
disease were collected during a short interview and from the patients’ records.
2.3. Assessment of Disease Activity
Disease activity was assessed using the Harvey Bradshaw Index (HBI) for CD and
Simple Clinical Colitis Activity Index (SCCAI) for UC. Remission was defined for a HBI
score
≤
4 points and SCCAI score
≤
1 point. In addition, all patients had a CRP level
lower than 5 mg/L at inclusion and last fecal calprotectin (within the last 6 months) below
150 ug/g.
2.4. Statistical Analysis
Statistical analysis of the data was performed using R version 4.1.2 (1 November 2021)
(©2021 The R Foundation for Statistical Computing).
In the univariate analysis, ttest, Chi-squared test and Fisher’s exact test were used
to determine whether there were significant differences between patients presenting with
fatigue and those without fatigue. Variables were selected taking into account the pre-
existing data in the literature [6,10,11,14,15,23–31].
Afterwards, a logistic regression model was determined using fatigue as the binary
dependent variable and the variables that had a pvalue < 0.2 in the univariate analysis
as predictors.
The statistical significance was considered as p< 0.05.
3. Results
Out of the 119 patients that were included in this study, 72 (60.5%) were male; the
median age was 39 years (IQR 30–47). Seventy-seven patients (64.7%) were diagnosed with
Medicina 2023,59, 532 4 of 10
CD and forty-two (35.3%) with UC, with a median disease duration of 6 years (IQR 2–10).
The median duration of remission was 23.5 months (IQR 10–32.5).
The characteristics of the study population, such as demographic data, data regarding
the treatment and the disease as well as the prevalence of symptoms of anxiety and
depression and the assessment of the HR-QoL are depicted in Table 1.
Table 1. Characteristics of the study population.
Characteristic
Sex Male, n (%)
Female, n (%)
72 (60.5%)
47 (39.5%)
Median age, years (IQR) 39 (30–47)
Phenotype Crohn’s disease, n (%)
Ulcerative colitis, n (%)
77 (64.7%)
42 (35.3%)
Median disease duration, years (IQR) 6 (2–10)
Active smoking, n (%) 41 (34.5%)
Treatment Biologic, n (%)
Conventional, n (%)
105 (88.2%)
14 (11.8%)
Type of biological treatmen
Infliximab, n (%)
Adalimumab, n (%)
Vedolizumab, n (%)
Ustekinumab, n (%)
53 (50.5%)
13 (12.3%)
34 (32.4%)
5 (4.8%)
Number of biological treatments 0–1, n (%)
>1, n (%)
91 (76.4%)
28 (23.5%)
History of IBD-related surgery, n (%) 37 (31.1%)
Anemia, n (%) 17 (14.3%)
Level of education
Low, n (%)
Medium, n (%)
High, n (%)
8 (6.7%)
48 (40.3%)
63 (52.9%)
Currently employed, n (%) 100 (84%)
FACIT-Fatigue Mean (±SD)
FACIT-F ≤40, n (%)
41.6 (±8.62)
46 (38.7%)
Mean IBDQ score (±SD) 189.4 (±24.1)
Symptoms of anxiety, n (%) 44 (37%)
Symptoms of depression, n (%) 25 (21%)
The vast majority of the patients (88.2%) were following a treatment with a biological
agent at the time of inclusion, most of them with infliximab (50.5%) and vedolizumab
(32.4%); a smaller proportion of patients were treated with adalimumab (12.3%) and ustek-
inumab (4.8%); and 11.8% of the patients were following a conventional treatment, either
with 5-ASA or azathioprine. Regarding the exposure to previous biological agents, 23.5% of
the patients had more than one biological treatment (they had at least one switch). Thirty-
seven patients (31.1%) had a history of IBD-related surgery (they underwent at least one
IBD-related surgical intervention). One-third of the patients (34.5%) were active smokers.
Regarding the level of education, 6.7% of patients had a low level of education (they
completed only the primary cycle of education), 40.3% had a medium level (they completed
high-school studies) and 52.9 had a high level of education (they graduated from university
or they had a master’s degree or PhD).
Anemia was identified in 14.3% of patients, all of them having only a mild form.
The mean FACIT-Fatigue score was 41.6 (SD
±
8.62), and 38.7% of patients were
revealed as having experienced fatigue when a cut-off value of 40 points was used (they
had a FACIT-Fatigue score
≤
40). The mean IBDQ 32 score was 189.4 (SD
±
24.1). Symptoms
of anxiety and depression were detected in 37% and 21% of the patients, respectively.
Endoscopic evaluation was not mandatory for inclusion in the study. However,
three patients were excluded due to proven endoscopic activity in spite of clinical and
Medicina 2023,59, 532 5 of 10
biochemical remission. Overall, 40 patients (33.6%) had at least one endoscopic evaluation
within the last year. Out of them, 21 had UC and 19 CD. Regarding the patients with UC, 13
underwent rectosigmoidoscopies, and 8 had complete colonoscopies. All patients with CD
had ileocolonoscopies. All patients were in endoscopic remission at their last evaluation.
Twenty-eight patients with CD (36.4% of CD patients) underwent CT/MRI enterogra-
phy or bowel ultrasound within the last year. Out of them, two had small bowel strictures,
without dilatation of small bowel loops. The strictures were clinically asymptomatic. Both
patients had normal ileocolonoscopies.
3.1. Univariate Analysis
Fatigue as assessed by the FACIT-Fatigue score was evaluated in different categories
of patients (Table 2).
Table 2. Univariate analysis of factors associated with fatigue.
Fatigue
(FACIT Fatigue ≤40)
Non-Fatigue
(FACIT Fatigue > 40)
Significance
(p)
Mean age, years (±SD) 39.1 (13.1) 40.2 (12.2) 0.66
Female sex, n (%) 27 (57.4) 20 (42.6) 0.001
CD Phenotype, n (%) 34 (44.2) 43 (55.8) 0.14
Mean disease duration,
years (±SD) 8.9 (8.4) 6.1 (4.9) 0.04
Active smoking, n (%) 16 (39) 25 (61) 0.86
Lower level of education, n (%)
6 (75) 2 (25) 0.04
>1 biological therapy, n (%) 18 (64.3) 10 (35.7) 0.003
Unemployment, n (%) 8 (42.1) 11 (57.9) 0.86
Anemia, n (%) 12 (70.6) 5 (29.4) 0.005
History of IBD-related surgery,
n (%) 16 (43.2) 21 (56.8) 0.62
Symptoms of anxiety, n (%) 35 (79.5) 9 (20.5) <0.001
Symptoms of depression, n (%)
22 (88) 3 (12) <0.001
HR-QoL, mean IBDQ32 (±SD) 168.5 (21.4) 202.6 (14.3) <0.001
Female sex was associated with higher levels of fatigue, with 57.4% of female patients
experiencing fatigue (p= 0.001). Regarding the disease duration, patients affected by fatigue
had a significantly longer disease duration (8.9 vs. 6.1 years, p= 0.04). Patients with a low
level of education also seemed to experience fatigue more frequently; however, the number
of patients with a low level of education included in this study was low.
Exposure to a higher number of biological agents was associated with higher levels
of fatigue: 64.3% of patients exposed to more than one biological therapy were affected
by fatigue (p= 0.003). Another factor associated with fatigue was anemia: the majority of
patients diagnosed with anemia also experienced fatigue (70.6%, p= 0.005). Anxiety and
depression strongly influenced the level of fatigue, with a significantly higher proportion
of patients with symptoms of anxiety (79.5%, p< 0.001) or depression (88%, p< 0.001)
having fatigue.
Health-related QoL, as measured by IBDQ 32 score, was strongly correlated with the
level of fatigue, with patients with fatigue having significantly lower scores (168.5 vs. 202.6
points, p< 0.001).
Age, disease phenotype, smoking status, employment status and history of IBD-related
surgery were not significantly associated with fatigue in our sample of patients.
3.2. Multivariate Analysis
A logistic regression model was determined by analyzing all variables that had a
pvalue < 0.2 in the univariate analysis.
Fatigue was significantly associated with lower HR-QoL (OR 2.21, 95% CI: 1.42–3.44,
p< 0.001
), symptoms of anxiety (OR 5.04, 95% CI: 1.20–21.22, p= 0.008), female sex (OR 3.32,
Medicina 2023,59, 532 6 of 10
95% CI: 1.02–10.76, p= 0.04) and with longer disease duration (OR 1.13, 95% CI: 1.01–1.27,
p= 0.04) (Table 3).
Table 3. Multivariate analysis of factors associated with fatigue in univariate analysis.
OR of Fatigue (95% CI) Significance (p)
Female sex 3.32 (1.02–10.76) 0.04
CD Phenotype 4.67 (0.89–24.37) 0.11
Longer disease duration * 1.13 (1.01–1.27) 0.04
Lower level of education 4.05 (0.27–60.01) 0.30
>1 biological therapy 1.13 (0.24–5.31) 0.87
Anemia 5.16 (0.54–48.45) 0.15
Symptoms of anxiety 5.04 (1.20–21.22) 0.008
Symptoms of depression 1.98 (0.32–11.99) 0.45
Lower HR-QoL †2.21 (1.42–3.44) <0.001
* one year increase, †ten points decrease in IBDQ score.
Other variables such as depression, disease phenotype, lower level of education, the
use of multiple biological therapies and anemia were not significantly associated with
fatigue in the multivariate analysis.
4. Discussion
This is, to our knowledge, the first study designed to evaluate fatigue in patients
with IBD in remission in Romania. It identified several factors associated with fatigue in
a population of patients that are considered to be optimally treated, without the need of
treatment optimization or surgical procedures, and it highlights the fact that even these
patients still have to deal with high levels of fatigue. The early detection of fatigue and
acting on factors that are associated with it could lead to a significant improvement in
patients’ HR-QoL and psychosocial status.
As our study shows, fatigue is a common symptom in patients with IBD in remission,
identified in up to 38.7% of the patients in our cohort. While other studies report similar
results [
27
,
28
], this percentage is, however, lower compared with data presented in a study
conducted by Villoria et al. that also assessed fatigue using the FACIT-Fatigue score with
the same cut-off value of 40 points. In this study conducted on 202 outpatients with inactive
IBD, fatigue was present in 54% of the patients; this may be explained by the fact that the
eligibility criteria in our study were more restrictive, and patients were also in biochemical
remission [10].
In our study population, fatigue was significantly associated with lower HR-QoL,
which is also confirmed by other studies [
14
,
27
,
29
,
30
,
32
]. However, the majority of them
are not focused on patients in remission. We identified a significant association between
fatigue and lower HR-QoL: patients with fatigue had significantly lower IBDQ 32 scores:
168.5 vs. 202.6 points (p< 0.001), which was also significant in the multivariate analysis.
Depression seems to be highly correlated with fatigue, as reported by multiple studies
in the literature [
14
,
23
,
29
–
31
]. Conversely, only a few of them report anxiety to be signifi-
cantly associated with fatigue in patients with inflammatory bowel disease, and even fewer
for patients in remission. In our study, even if they were both significantly associated with
fatigue in the univariate analysis, in the multivariate analysis only anxiety was significantly
associated with fatigue (OR 5.04, 95% CI: 1.20–21.22, p= 0.008).
Female sex is a well-known factor associated with fatigue [
14
,
24
,
25
,
28
,
29
,
33
]. Similar
to general population, in our group of patients, fatigue was strongly associated with
female sex. This association is confirmed by several other studies performed on IBD
patients [7,27,28,31,34].
Patients with a longer disease duration may have experienced a more protracted
course and may have had multiple relapses or surgical interventions. In our study, this
group of patients was affected more frequently by fatigue. Conversely, other studies report
Medicina 2023,59, 532 7 of 10
lower levels of fatigue in patients with longer disease durations, which could be explained
by the adjustment to the chronic disease over time [28].
Fatigue was not associated with previous IBD-related surgeries. Even if there are stud-
ies in the literature reporting that IBD-related surgery is associated with fatigue [
26
], other
studies did not find a significant association [
10
,
30
], and others report an improvement of
fatigue and HR-QoL after surgery [
35
,
36
]. Patients that had bowel strictures and underwent
surgical resection may have an improved food-related quality of life and may be less prone
to restrictive dietary behavior due to the alleviation of obstructive symptoms [
37
]. In addi-
tion, patients with ileal resection were systematically assessed for vitamin B12 deficiency
and supplemented if necessary, which may have contributed to the improvement of fatigue
in our study.
Anemia, even if it was significantly associated with fatigue in the univariate analysis,
was not significant in the multivariate analysis. However, data reported in the literature are
divergent. While some studies report the lack of association between fatigue and anemia or
iron deficiency in patients with inactive disease [
7
,
38
], others found an association between
hemoglobin levels and fatigue [6,23,27].
Vitamin and micronutrients deficiencies may play an important role in the etiology
of fatigue [
6
]. Although they were not specifically assessed in this study, as previously
mentioned, vitamin B12 level was systematically assessed in patients with ileal resection as
part of the IBD management. Fifteen patients had ileal resection; out of them, six developed
vitamin B12 deficiency and received supplementation. Similarly, patients with anemia
were assessed for iron, vitamin B12 and folic acid deficiencies. All patients identified with
deficiencies received supplementations accordingly.
Even though the vitamin D level was not routinely assessed, an important proportion
of patients treated in our center use vitamin D supplements. However, the association
between fatigue and vitamin D deficiency in patients with IBD is controversial. While
some studies found an association between muscle fatigue and lower vitamin D level [
39
],
others report that vitamin D deficiency is not associated with fatigue in patients with
IBD [30,40,41].
Strengths and Limitations
The study analyzed fatigue in patients with IBD in both clinical and biochemical
remission, in correlation with anxiety, depression and HR-QoL. It was conducted on
a population of patients that were considered to be optimally treated. Several factors
associated with fatigue were identified, such as lower HR-QoL, anxiety, female sex and
longer disease duration.
On the other hand, it has several limitations, such as the inability to establish the
causality due to its cross-sectional design; disease remission was evaluated on clinical and
biochemical bases, without colonoscopies performed at inclusion. Given the fact that this
was a single-center study and the prevalence of IBD in Romania is low [
42
], the sample
size was limited. Another possible limitation is that the patients were treated in a tertiary
gastroenterology center and because of this fact they may have had a more severe disease.
5. Conclusions
In summary, this study showed that even in patients with inactive IBD there is a high
prevalence of fatigue. In addition, it identified factors that are significantly associated with
fatigue: lower HR-QoL, anxiety, as well as other clinical factors such as longer disease
duration and female sex.
Because fatigue is a multifactorial and complex condition, further research with larger
groups of patients and multicenter trials should focus on identifying other predictive or
etiological factors for fatigue in patients with IBD.
Medicina 2023,59, 532 8 of 10
Author Contributions:
Conceptualization, T.S. and M.D.; methodology, T.S., C.P. and A.C.; validation,
M.D., C.G. and L.G.; formal analysis, T.S., C.P. and A.C.; investigation, T.S. and C.M.; resources,
M.D., A.C., C.M. and C.G.; data curation, D.I.; writing—original draft preparation, T.S.; writing—
review and editing, D.I. and C.M.; visualization, M.D. and M.M.; supervision, M.D. and M.M.;
project administration, M.D. and T.S. All authors have read and agreed to the published version of
the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement:
The study was conducted in accordance with the Declaration
of Helsinki, and approved by the Ethics Committee of Fundeni Clinical Institute (Approval Code:
40545; Approval Date: 7 June 2021).
Informed Consent Statement:
Informed consent was obtained from all subjects involved in the study.
Data Availability Statement:
The data presented in this study are available on request from the
corresponding author.
Conflicts of Interest: The authors declare no conflict of interest.
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