Understanding fatigue among Japanese patients with inflammatory bowel disease: insights from international comparisons and meta-analysis

Makoto Tanaka; Momoko Takai; Sayaka Wakai; Kayoko Sakagami; Hiroaki Ito

doi:10.5217/ir.2024.00145

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Original Article Understanding fatigue among Japanese patients with inflammatory bowel disease: insights from international comparisons and meta-analysis: Makoto Tanaka^1,, Momoko Takai², Sayaka Wakai¹, Kayoko Sakagami³, Hiroaki Ito³; DOI: https://doi.org/10.5217/ir.2024.00145
Published online: January 22, 2025

¹Graduate School of Health Care Sciences, Institute of Science Tokyo, Tokyo, Japan

²Department of Nursing, Institute of Science Tokyo Hospital, Tokyo, Japan

³Kinshukai Infusion Clinic, Osaka, Japan

Correspondence to Makoto Tanaka, Graduate School of Health Care Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. E-mail: hmakoto-tky@umin.ac.jp

• Received: September 13, 2024 • Revised: November 13, 2024 • Accepted: November 17, 2024

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Abstract
INTRODUCTION
METHODS
RESULTS
DISCUSSION
NOTES
Supplementary Material
REFERENCES

Abstract

Background/Aims
Fatigue is a common symptom in patients with inflammatory bowel disease (IBD). The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale has demonstrated reliability and validity in assessing fatigue in patients with IBD and is used worldwide. This study aimed to examine the current state of fatigue among Japanese patients with IBD using the FACIT-F scale and to compare these findings with data from global studies through a systematic review.
Methods
Data from 488 patients with IBD treated at a specialized IBD clinic were analyzed. Patient characteristics, such as sex, age, disease duration, disease activity, FACIT-F scores, and sleep duration, were collected. A literature search identified 8 studies that met our inclusion criteria for an international comparison. A meta-analysis was performed on the Fatigue Subscale (FS) scores of FACIT-F to estimate the pooled mean.
Results
The mean FACIT-F (FS) score in this study was 39.9 ± 8.6. Four variables were significantly associated with fatigue: low Emotional Well-Being subscale scores, sleep duration < 6 hours, albumin level below the reference value, and being unmarried. The meta-analysis revealed that the pooled mean score was 40.2 (95% confidence interval, 39.5–40.9), and between-study heterogeneity was moderate (I² = 41%).
Conclusions
The FACIT-F (FS) scores and related factors in Japanese patients with IBD demonstrated a similar trend to those in other countries. These findings can be used to identify patients in need of support and to consider interventions for modifiable factors. This study will help promote international collaborative research.
Keywords: Inflammatory bowel diseases; Ulcerative colitis; Crohn disease; Fatigue; Meta-analysis

INTRODUCTION

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract characterized by periods of exacerbation and remission. It encompasses 2 diseases that typically manifest in early adulthood: ulcerative colitis (UC) and Crohn’s disease (CD). The etiology of both conditions remains unclear, and the presenting symptoms include diarrhea, abdominal pain, bloody stools, and extraintestinal manifestations in the joints and skin [1-3]. The development of effective therapeutics that enable better disease control has improved the management of IBD. However, previous research indicates that many patients experience difficulties in their daily lives, even during remission periods [4,5]. Fatigue, which significantly impacts patients’ quality of life and induces disease-related anxiety, has been recognized as a crucial concern in IBD research, especially in Europe. A common symptom of IBD, fatigue is associated with decreased health-related quality of life [6]. Previous studies report fatigue prevalence rates of 72% during active disease and of 47% during remission, indicating that fatigue persists even when the disease is quiescent [5]. While the exact causes of fatigue in patients with IBD are not fully understood, factors, such as sleep disturbance, anxiety, depression, and anemia, have been implicated [5,7]. Fatigue in patients with IBD has been identified as a high-priority research topic in Europe [8], with ongoing studies investigating the relationship between IBD and fatigue. However, research specifically focusing on fatigue in patients with IBD in Japan is lacking. Therefore, it is essential to elucidate the current status of fatigue among Japanese patients with IBD to facilitate the identification of its causes and development of intervention strategies. It would also contribute to expanding global knowledge and gaining an understanding of cultural and social diversity.

Several questionnaires for fatigue assessment have been developed and used in studies on patients with IBD. A systematic review of IBD-related fatigue estimated its prevalence by a meta-analysis, but extremely high heterogeneity (due to diverse disease statuses and use of different questionnaires and definitions) and most studies originating from North America and Europe were mentioned as limitations [5]. No clear consensus exists on the best questionnaire to use in IBD, but the use of the Multidimensional Fatigue Inventory [9] and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale [10] is particularly common [5,7]. The FACIT-F scale [10], in addition to being brief and easy to understand, has demonstrated reliability and validity for measuring fatigue in patients with IBD [11]. The scale is used worldwide, and its results can be compared with those in the general population and several other chronic diseases. Therefore, this study aimed to investigate fatigue in patients with IBD using the FACIT-F scale and to elucidate the current status and associated factors of fatigue among patients with IBD in Japan while also conducting an international comparison of the results through a systematic review.

METHODS

1. Study Design and Participants

This study is an international comparative study based on a single-center, cross-sectional survey and a systematic review. The recruitment period for the cross-sectional study was set from June 2022 to July 2022 based on the outpatient intervals of patients with IBD. During this period, patients aged ≥ 20 years who attended a specialized clinic in a metropolitan area for the purpose of UC or CD treatment, were capable of understanding Japanese documents, and could respond to the survey questionnaire were targeted. The nursing staff at the facility where the survey was conducted informed the patients of the study. An envelope containing an informed consent document approved by the ethics review committee, a questionnaire, and a consent withdrawal form was provided. The patients were required to read the explanatory document, answer the questionnaire if willing to cooperate, and submit it using a collection box within the clinic. Among the 499 patients recruited using this method, 488 were included in the final analysis after excluding those with missing responses regarding patient characteristics, non-responses to the Fatigue Subscale (FS) of the FACIT-F, or identical responses to all items. This study was conducted in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments and Ethical Guidelines for Medical and Health Research Involving Human Subjects (as revised on March 23, 2021). Approval was obtained from the Ethics Review Committee of the Faculty of Medicine of Tokyo Dental and Medical University and Kinshukai Hanwa-Sumiyoshi Hospital Ethics Committee (approval no. M2021-396, 2022-8).

2. Study Selection

The selection of papers for international comparison was conducted via a literature search of PubMed, CINAHL, and Web of Science. The inclusion criteria comprised the following: (1) studies that reported the FACIT-F FS score in adult patients with IBD including both UC and CD; (2) studies with full-text access; and (3) peer-reviewed articles. In contrast, the exclusion criteria comprised the following: (1) non-primary sources, including review articles and proceedings; and (2) studies published in languages other than English and Japanese. There were no restrictions on the year of publication in the search strategy. The search was conducted using the search query “inflammatory bowel disease” OR “Crohn’s disease” OR “ulcerative colitis” AND “fatigue” AND “FACIT-F OR FACIT OR FACIT-Fatigue” on March 21, 2024. The selection process for this systematic review is illustrated in Fig. 1. After excluding duplicates, 28 articles were identified. Studies that were systematic reviews, lacked detailed FACIT-F FS score results, involved pediatric patients, did not provide UC and CD survey results, evaluated specific treatment modalities, or used the same survey results were excluded. Ultimately, 8 articles were included in the analysis [6,11-17].

The data analysis involved extracting the study population backgrounds and FACIT-F (FS) scores from each study and organizing them in Excel. For studies presenting mean and standard deviation, independent sample t-tests using summary data were conducted to compare the results with those of the current study.

3. Questionnaire Items

The questionnaire administered to the participants contained items regarding patient characteristics (sex, age, marital status, job status, duration of illness, and current treatment), height, weight, and sleep duration and the FACIT-F scale. Disease-related information was collected from medical records, including disease name, disease activity, and blood data (C-reactive protein, hemoglobin, and albumin levels).

1) Disease Activity

Disease activity was determined using the Crohn’s Disease Activity Index (CDAI) [18,19] and partial Mayo score (pMayo) [20]. The CDAI is an index used to classify the severity of CD, with scores of ≥ 150 indicating quiescent disease and > 450 indicating severe disease [19]. The pMayo is used to classify the severity of UC, with scores of 0–1 indicating remission and ≥ 2 indicating active disease [1].

2) FACIT-F

The FACIT-F is used to evaluate the degree of fatigue and its impact on daily activities and functioning in patients with chronic illnesses. It consists of a 40-item scale with 5 subscales (Physical Well-Being, Social/Family Well-Being, Emotional Well-Being [EWB], Functional Well-Being, and Fatigue) assessing fatigue over the past 7 days and its impact on daily life. Respondents select their response from “not at all (0 points),” “a little bit (1 point),” “somewhat (2 points),” “quite a bit (3 points),” and “very much (4 points).” The FS of the FACIT-F was used to measure fatigue in patients with IBD. The FACIT-F (FS) has 13 items and a maximum score of 52, with higher scores indicating less fatigue. Additionally, the EWB subscale of the FACIT-F was used to assess emotional status. The EWB subscale has a maximum score of 24, with higher scores indicating greater EWB [10].

4. Data Analysis

Categorical variables were presented as numbers and percentages, while continuous variables were presented as mean ± standard deviation. Albumin and hemoglobin data were dichotomized into groups below and above the reference values (albumin: 3.8 g/dL, hemoglobin: 13.5 g/dL for males, 11.3 g/dL for females). CDAI scores < 150 were classified as remission in patients with CD, while scores ≥ 150 were classified as active disease [19]. pMayo scores of 0–1 were considered remission in patients with UC, while scores ≥ 2 were considered as active disease [1]. Six hours was used as a reference for short sleep duration based on previous studies, and the sleep duration data were dichotomized into the < 6 hours and ≥ 6 hours groups [21].

FACIT-F (FS) was set as the dependent variable, and other variables presumed to be associated with fatigue were set as independent variables. For the comparison of data between the 2 groups, t-tests were used, and Pearson correlation coefficients were calculated for continuous variables. Variables with a P-value < 0.2 in the bivariate analysis and diagnosis (UC/CD) were included in the multiple regression analysis. The C-reactive protein levels were excluded as independent variables owing to the association with disease activity. We checked the variance inflation factor of the multiple regression model using a value > 10 as an indicator of multicollinearity. The above statistical analyses were performed using IBM SPSS ver. 29.0J for Windows (IBM Corporation, Armonk, NY, USA). Statistical significance was set at P< 0.05.

The meta-analysis was performed using RevMan 5.4 (The Cochrane Collaboration, Copenhagen, Denmark). The pooled mean FACIT-F (FS) score was estimated using a random-effects model. We calculated standard errors from sample sizes and standard deviations for all papers that provided means and standard deviations and included them in our analysis. We also estimated the pooled mean FACIT-F (FS) scores for patients in remission, patients with CD, and patients with UC using studies that specified the mean for each of these groups. Results were visualized using forest and funnel plots, and heterogeneity was assessed using I², tau-square, and chi-square statistics.

RESULTS

1. Current Study

Among the 488 patients, 320 (65.6%) were male (Table 1). The mean patient age was 43.4 ± 12.7 years. Two hundred and four patients (41.8%) were diagnosed with UC, and 284 (58.2%) were diagnosed with CD, with a mean duration of illness of 16.2 ± 8.5 years. Patients with active disease accounted for 13.7% of the total study population. The mean FACIT-F (FS) score was 39.9 ± 8.6. Variables significantly associated with FACIT-F (FS) scores in the bivariate analysis were sex (P = 0.013), occupation (P= 0.001), marital status (P= 0.001), sleep status (P< 0.001), EWB subscale score (P< 0.001), disease activity (P< 0.001), and albumin levels (P< 0.001).

The results of the multiple regression analysis are shown in Table 2. The variance inflation factor for all variables was < 10.0, indicating no multicollinearity issues. The probability of analysis of variance was considered significant at P< 0.001. Four variables were significantly associated with fatigue: low EWB subscale scores, sleep duration < 6 hours, albumin level below the reference value, and being unmarried (Table 2). These variables were related to lower FACIT-F (FS) scores, indicating greater fatigue. Based on the finding that marital status was significantly related to fatigue, a post-hoc analysis was conducted to determine the effects of the interaction between sex and marital status on fatigue. The results revealed no significant association (P= 0.10).

2. International Comparison and Meta-Analysis

The 8 studies identified through the systematic review and our current study are summarized and presented in Table 3. These studies included 119 to 1,185 participants aged approximately 35–55 years, with proportions of males ranging from 39% to 66%. The mean duration of illness was approximately 10 years, and the proportions of diseases and active phases varied among the study populations. Among the 9 studies, 2 studies were conducted solely on patients in clinical remission. The overall mean FACIT-F (FS) scores ranged from 38.9 ± 11.0 to 41.6 ± 8.6, with median scores ranging from 30 (range, 22–39) to 41 (range, 35–47). The mean FACIT-F (FS) scores were not significantly different from those obtained in the current study. Across all countries, the FACIT-F (FS) scores were higher in patients in remission than in those with the active phase of the disease, in males than in females, and in patients with UC than in those with CD.

The meta-analysis included 6 studies, each reporting their respective means and standard deviations (Fig. 2). The pooled mean FACIT-F (FS) score was 40.2 (95% confidence interval, 39.5–40.9), and between-study heterogeneity was moderate (I² = 41%), and the chi-squared test was not significant (P= 0.13). The variability between studies was small (τ² = 0.31), suggesting a satisfactory level of reliability of the results. The funnel plot was almost symmetrical (Fig. 3). The results of the subgroup analysis involving a meta-analysis of studies in which means and standard deviations were available for patients in remission are shown in Fig. 4. Further, the results of the separate meta-analyses for patients with CD and those with UC are presented in Supplementary Figs. 1 and 2.

DISCUSSION

In the international comparisons, the mean FACIT-F (FS) score of Japanese patients with IBD was not significantly different than that of patients with IBD in Europe, the United States, or Asia [6,11-17]. Although not compared with the general population in Japan, patients with IBD in the current study experienced significant fatigue compared with the general population in the United States with scores of 43.6 ± 9.4 [22] and in Germany with scores of 43.5 ± 8.3 [23]. The FACIT-F (FS) scores were not significantly different between patients with UC and CD. However, since the study was conducted in an outpatient setting, most patients were in remission. Therefore, it should be noted that the data are not representative of all IBD patients in Japan. Multiple regression analysis revealed that the EWB subscale score, sleep duration, albumin levels, and marital status were significantly associated with fatigue.

The EWB subscale scores had the most significant association with the FACIT-F (FS) scores in the current study. Previous studies have reported an association between fatigue and depression in patients with IBD [7,24-26]. Although the severity of depression was not assessed in the current study, an association between mental health and fatigue was indicated, which is consistent with the results of previous research.

Similarly, sleep duration was significantly associated with fatigue in the current study, which is consistent with the findings of previous studies [7,26-28]. Sleep disturbances are more common in patients with IBD than in the general population [29]. Sleep disturbances may exacerbate chronic inflammation [29], highlighting the importance of improving sleep quality to enhance the quality of life in patients with IBD. There was a lack of data on the use of sleeping pills in this study, even though patients who used sleeping pills to improve sleep may have been included. Such data would be valuable for understanding potential confounding effects and will be important to consider in future research.

Furthermore, the relationship between albumin levels and fatigue was evident in the multiple regression analysis conducted in this study. Patients with IBD are prone to malnutrition and have significantly lower serum albumin concentrations than the general population [30]. Dietary improvements via lifestyle interventions have been shown to reduce fatigue [31], indicating that improving the nutritional status of patients with IBD may reduce fatigue. Albumin levels may also reflect the disease activity of patients with IBD [30], potentially influencing the observed association between disease activity and fatigue in the bivariate analysis in this study. There was a significant difference between the remission and active periods with a difference of 5 points in the bivariate analysis. In the multivariate analysis, other variables were more influential, and adjustment eliminated significant associations. However, the relationship between disease activity and fatigue remains controversial [32].

The current study observed a significant association between marital status and fatigue, with unmarried patients experiencing greater fatigue than married patients. Fatigue in patients with IBD may be related to significant difficulties in performing household activities, such as grocery shopping and cooking, indicating that the lack of support from a spouse may further exacerbate fatigue [33]. Given the responsibilities associated with housework, the impact of marital status on fatigue may differ between men and women, and further investigation of this relationship would be beneficial. Although we did not collect data on cohabitating families in this study, it would also be worthwhile to examine whether or not a patient who is single lives with a family member. Furthermore, in Japan, unmarried individuals, particularly those without children, often face social expectations to compensate by taking on more work responsibilities, which impacts work-life balance [34] and potentially contributes to higher fatigue levels. This social structure can limit their support networks compared to those of married individuals, who may benefit from more stable family support. The pressure placed on unmarried individuals aligns with broader cultural expectations related to work dedication and personal responsibilities in Japan [34], which could be contributing factors to the fatigue-related findings. According to a systematic review focusing on factors contributing to fatigue [26], this has not been reported previously apart from in Japan4; therefore, it may be a cultural trait.

Common findings across different countries include higher FACIT-F (FS) scores during remission than during active disease, higher scores in males than in females, and higher scores in patients with UC than in those with CD [32-36]. The compilation of more results of studies on the fatigue levels of patients with IBD in various countries using the FACIT-F scale will contribute to further research.

This study is not without limitations. First, only outpatients were included, which resulted in few cases of severe disease. The relationship between disease activity and fatigue is unclear, and investigating fatigue in patients with severe IBD, such as those requiring hospitalization, may be beneficial in determining this relationship. Second, an R² value of 0.386 in the multiple regression analysis indicates that not all variables related to fatigue were adequately included. Variables such as comorbidities, daily physical activity levels, and personal roles or responsibilities may exert a significant influence and were not measured in this study. It could be beneficial to assess these in future research to gain a better understanding of their contributions to fatigue. Lastly, studies that only presented categorized results with FACIT-F (FS) scores classified by certain values were excluded, and few studies were included for international comparisons, making it challenging to compare fatigue levels among patients with IBD. Furthermore, owing to differences in the reporting styles, not all studies provided data suitable for statistical comparisons, leading to speculative interpretations.

However, this relatively large-scale survey study involving 488 participants summarizes descriptive statistics regarding diseases, disease activity, and other variables related to fatigue in Japanese patients with IBD, facilitating international comparisons. The results of this study will contribute to the advancement of research on fatigue in patients with IBD.

In conclusion, factors associated with fatigue in Japanese patients with IBD were identified as EWB scale scores, sleep duration, serum albumin levels, and marital status. These can be used to identify patients in need of support and to consider interventions for modifiable factors. The FACIT-F (FS) scores and related factors in Japanese patients with IBD demonstrated a similar trend to those in other countries. We have added knowledge from Asia, where knowledge on fatigue in IBD is scarce, expanded on the world’s knowledge on the condition, and provided resources for cultural reflection. This study will help promote international collaborative research.

NOTES

Funding Source

This work was supported by JSPS KAKEN (Grant Number JP22K10893).

Conflict of Interest

No potential conflict of interest relevant to this article was reported.

Data Availability Statement

The data supporting the findings of this study are not publicly available owing to ethics committee formalities but are available from the corresponding author upon reasonable request.

Author Contributions

Conceptualization: Tanaka M, Takai M, Sakagami K, Ito H. Data curation: Tanaka M, Takai M. Formal analysis and interpretation of the results: Tanaka M, Takai M, Wakai S. Funding acquisition: Tanaka M. Investigation: Tanaka M, Takai M, Sakagami K. Methodology: Tanaka M, Takai M, Wakai S. Project administration: Tanaka M. Resources: Tanaka M, Ito H. Validation: Tanaka M, Takai M, Wakai S, Sakagami K, Ito H. Visualization: Tanaka M, Takai M. Writing - original draft preparation: Tanaka M, Takai M. Writing - review and editing: Wakai S, Sakagami K, Ito H. Approval of final manuscript: all authors.

Supplementary Material

Supplementary materials are available at the Intestinal Research website (https://www.irjournal.org).

Supplementary Fig. 1.

Subgroup analysis in patients with Crohn’s disease: Pooled mean FACIT-F (FS) score estimated by meta-analysis. FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; FS, Fatigue Subscale; IV, interval variable; CI, confidence interval; SE, standard error.

ir-2024-00145-Supplementary-Figs.pdf

Supplementary Fig. 2.

Subgroup analysis in patients with ulcerative colitis: Pooled mean FACIT-F (FS) score estimated by meta-analysis. FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; FS, Fatigue Subscale; IV, interval variable; CI, confidence interval; SE, standard error.

ir-2024-00145-Supplementary-Figs.pdf

Fig. 1.

PRISMA 2020 flow diagram of study selection. PRISMA, Preferred Reporting Items for Systematic reviews and Meta-Analyses; FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue.

Fig. 2.

Pooled mean FACIT-F (FS) score estimated by meta-analysis. FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; FS, Fatigue Subscale; SE, standard error; IV, interval variable; CI, confidence interval.

Fig. 3.

Funnel plot of the mean FACIT-F (FS) score. FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; FS, Fatigue Subscale; SE, standard error.

Fig. 4.

Subgroup analysis in patients with IBD in clinical remission: Pooled mean FACIT-F (FS) score estimated by meta-analysis. IBD, inflammatory bowel disease; FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; FS, Fatigue Subscale; SE, standard error; IV, interval variable; CI, confidence interval.

Table 1.

Participants’ Backgrounds and Bivariate Analysis Results

Variable	UC (n = 204)	CD (n = 284)	Total (n = 488)	FACIT-F (FS)^a	Pearson r	P-value
Age (yr)	45.4 ± 14.3	42.0 ± 11.3	43.4 ± 12.7		–0.001	0.983
Sex (n = 487)						0.013
Male	111 (54.4)	209 (73.6)	320 (65.7)	40.6 ± 8.3
Female	93 (45.6)	74 (26.1)	167 (34.3)	38.5 ± 8.9
Diagnosis						0.669
UC	204 (100)	0	204 (41.8)	40.1 ± 7.9
CD	0	284 (100)	284 (58.2)	39.8 ± 9.1
Job status (n = 486)						0.001
No job	42 (20.6)	34 (12.0)	76 (15.6)	36.5 ± 9.7
Working or student	160 (78.4)	250 (88.0)	410 (84.4)	40.6 ± 8.2
Marital status (n = 487)						0.001
Single	76 (37.3)	125 (44.2)	201 (41.3)	38.3 ± 9.4
Married	128 (62.7)	158 (55.8)	286 (58.7)	41.0 ± 7.8
Disease duration (yr)	14.3 ± 8.2	17.5 ± 8.4	16.2 ± 8.5		–0.039	0.392
BMI (kg/m²)	22.2 ± 4.5	22.5 ± 3.5	22.4 ± 4.0		0.063	0.167
Disease phase (n = 483)						< 0.001
Remission	162 (79.4)	254 (91.0)	417 (86.3)	40.6 ± 8.2
Active	41 (20.1)	25 (9.0)	66 (13.7)	35.6 ± 9.6
Biologics						0.982
Presence	68 (33.3)	249 (87.7)	317 (65.0)	39.9 ± 8.9
Absence	136 (66.7)	35 (12.3)	171 (35.0)	39.9 ± 8.1
Sleep status						< 0.001
< 6 hr	50 (24.5)	85 (29.9)	135 (27.7)	37.0 ± 9.5
≥ 6 hr	154 (75.5)	199 (70.1)	353 (72.3)	41.0 ± 7.9
CRP level (mg/dL)	0.11 ± 0.29	0.23 ± 0.69	0.19 ± 0.58
Hemoglobin concentration (n = 434)						0.090
Low^b	19 (12.4)	59 (21.0)	74 (17.1)	38.4 ± 9.1
Normal range^c	134 (87.6)	222 (79.0)	360 (82.9)	40.3 ± 8.5
Albumin levels (n = 431)						< 0.001
< 3.8 g/dL	13 (8.7)	49 (17.4)	43 (10.0)	35.3 ± 12.2
≥ 3.8 g/dL	137 (91.3)	232 (82.6)	388 (90.0)	40.5 ± 8.1
Emotional Well-Being	18.0 ± 4.1	17.9 ± 4.5	18.0 ± 4.3		0.594	< 0.001

^a Possible score range is (0–52), with higher scores indicating less fatigue impact.

^b Male (<13.5 g/dL), female (<11.3 g/dL).

^c Male (≥13.5 g/dL), female (≥11.3 g/dL).

UC, ulcerative colitis; CD, Crohn’s disease; FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; FS, Fatigue Subscale; BMI, body mass index; CRP, C-reactive protein.

Table 2.

Factors Affecting the FACIT-F (FS) Score

Factor	β	B (95% CI)	P-value
Female/male (ref)	–0.06	–1.09 (–2.67 to 0.51)	0.181
Working or student/no job (ref)	0.08	1.94 (–0.10 to 3.99)	0.062
Single/married (ref)	–0.08	–1.44 (–2.84 to –0.04)	0.044
CD/UC (ref)	–0.05	–0.84 (–2.33 to 0.65)	0.267
BMI	–0.02	–0.05 (–0.25 to 0.15)	0.614
Sleep time ≤ 6 hr/ > 6 hr (ref)	–0.11	–2.14 (–3.69 to –0.58)	0.007
Emotional Well-Being	0.51	1.05 (0.88 to 1.22)	< 0.001
Active disease/in remission (ref)	–0.08	–2.09 (–4.27 to 0.09)	0.060
Hemoglobin level low/normal range (ref)	0.01	0.18 (–1.77 to 2.14)	0.855
Albumin level low/normal range (ref)	–0.10	– 2.92 (–5.37 to –0.46)	0.020

R²=0.386, analysis of variance P<0.001.

FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; FS, Fatigue Subscale; β, standardized partial regression coefficient; B, unstandardized regression coefficient; CI, confidential interval; ref, reference category; CD, Crohn's disease; UC, ulcerative colitis; BMI, body mass index.

Table 3.

International Comparison of the Study Population and the Results of Fatigue in Inflammatory Bowel Disease Patients

Variable	Current study (2023)	Villoria et al. (2017) [12]	Williet et al. (2017) [13]	Tinsley et al. (2011) [11]	Saraiva et al. (2019) [14]	Tiankanon et al. (2021) [15]	Gatt et al. (2019) [16]	Stroie et al. (2023) [6]	Christensen et al. (2022) [17]
Country	Japan	Spain	France	USA	Portugal	Thailand	5 Countries^a	Romania	Denmark
Sample size	488	177	1,185	209	105	209	158	119	300
Age (yr)	43.4 ± 12.7	39.0 ± 12.0	45 (34–60)	38.6 ± 12.6	51.2 ± 15.8	47.3 ± 15.7	35.1 ± 12.8	39 (30–47)
Male sex (%)	66	58	39	47	43	49	51	61	54
Disease duration (yr)	16.2 ± 8.5	9.0 ± 6.0	14 (7–22)		13.4 (6.8–13.0)			6 (2–10)
BMI (kg/m²)	22.4 ± 4.0	25.0 ± 4.4	22.7 (20.4–25.6)
CD (%)	58	72	61	63	57	49	63	65	63
Active (%)	13.7	Few^b	62.9	16.7	Few^b	48.0	0	0
FACIT-F score^c
Overall	39.9 ± 8.6	38	30 (22–39)	38.9 ± 11.0	39.6 ± 9.7	40.9 ± 8.5	40.1 ± 12.2	41.6 ± 8.6	39
Overall	41 (35–47)
Remission	40.6 ± 8.2		36 (28–44)			42.5 ± 7.2	40.1 ± 12.2	41.6 ± 8.6
Remission	42 (36-47)
Active	35.6 ± 9.6					39.2 ± 9.4
Active	38 (31–42)
Male	40.6 ± 8.3	39.0 ± 11.0					41.1
Male	42 (36–47)
Female	38.5 ± 8.9	30 ± 13					39.0
Female	40 (34–45)
CD	39.8 ± 9.1	35.0 ± 12.0	30 (21–39)	38.6 ± 11.3			38.9 ± 12.2		39 (28–45)
CD	41 (35–47)
UC	40.1 ± 7.9	39 ± 11	31 (23–40)	39.4 ± 10.6			42.2 ± 12.0		40 (32–46)
UC	41 (36–46)

Based on the values reported in each study, summary statistics for continuous variables are presented as mean±SD and/or median (IQR).

^a Greece, Cyprus, Malta, Hungary, and Israel.

^b Most patients were in clinical remission.

^c Possible score range is (0–52), with higher scores indicating less fatigue impact.

BMI, body mass index; CD, Crohn’s disease; FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; UC, ulcerative colitis; SD, standard deviation; IQR, interquartile range.

REFERENCES

1. Nakase H, Uchino M, Shinzaki S, et al. Evidence-based clinical practice guidelines for inflammatory bowel disease 2020. J Gastroenterol 2021;56:489–526.Article PDF
2. Lamb CA, Kennedy NA, Raine T, et al. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut 2019;68(Suppl 3): s1–s106.Article PubMed PMC
3. Lichtenstein GR, Loftus EV, Isaacs KL, Regueiro MD, Gerson LB, Sands BE. ACG clinical guideline: management of Crohn’s disease in adults. Am J Gastroenterol 2018;113:481–517.Article PubMed
4. Tanaka M, Kazuma K. Ulcerative colitis: factors affecting difficulties of life and psychological well being of patients in remission. J Clin Nurs 2005;14:65–73.Article PubMed
5. D’Silva A, Fox DE, Nasser Y, et al. Prevalence and risk factors for fatigue in adults with inflammatory bowel disease: a systematic review with meta-analysis. Clin Gastroenterol Hepatol 2022;20:995–1009.Article PubMed
6. Stroie T, Preda C, Meianu C, et al. Fatigue is associated with anxiety and lower health-related quality of life in patients with inflammatory bowel disease in remission. Medicina (Kaunas) 2023;59:532.Article PubMed PMC
7. Borren NZ, van der Woude CJ, Ananthakrishnan AN. Fatigue in IBD: epidemiology, pathophysiology and management. Nat Rev Gastroenterol Hepatol 2019;16:247–259.Article PubMed PDF
8. Dibley L, Bager P, Czuber-Dochan W, et al. Identification of research priorities for inflammatory bowel disease nursing in Europe: a Nurses-European Crohn’s and Colitis Organisation Delphi Survey. J Crohns Colitis 2017;11:353–359.Article PubMed
9. Smets EM, Garssen B, Bonke B, De Haes JC. The Multidimensional Fatigue Inventory (MFI) psychometric qualities of an instrument to assess fatigue. J Psychosom Res 1995;39:315–325.Article PubMed
10. FACIT.org. Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) [Internet]. c2024 [cited 2024 Mar 15]. https://www.facit.org/measures/facit-f.
11. Tinsley A, Macklin EA, Korzenik JR, Sands BE. Validation of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) in patients with inflammatory bowel disease. Aliment Pharmacol Ther 2011;34:1328–1336.Article PubMed
12. Villoria A, García V, Dosal A, et al. Fatigue in out-patients with inflammatory bowel disease: prevalence and predictive factors. PLoS One 2017;12:e0181435.Article PubMed PMC
13. Williet N, Sarter H, Gower-Rousseau C, et al. Patient-reported outcomes in a French nationwide survey of inflammatory bowel disease patients. J Crohns Colitis 2017;11:165–174.Article PubMed
14. Saraiva S, Cortez-Pinto J, Barosa R, et al. Evaluation of fatigue in inflammatory bowel disease: a useful tool in daily practice. Scand J Gastroenterol 2019;54:465–470.Article PubMed
15. Tiankanon K, Limsrivilai J, Poocharoenwanich N, et al. Burden of inflammatory bowel disease on patient mood, fatigue, work, and health-related quality of life in Thailand: a case-control study. Crohns Colitis 360 2021;3–otab077.Article PubMed PDF
16. Gatt K, Schembri J, Katsanos KH, et al. Inflammatory bowel disease [IBD] and physical activity: a study on the impact of diagnosis on the level of exercise amongst patients with IBD. J Crohns Colitis 2019;13:686–692.Article PubMed
17. Christensen KR, Ainsworth MA, Steenholdt C, et al. Fatigue is a systemic extraintestinal disease manifestation largely independent of disease activity, chronicity, and nutritional deficiencies in inflammatory bowel disease on biologics. Scand J Gastroenterol 2022;57:1051–1057.Article PubMed
18. Best WR, Becktel JM, Singleton JW. Rederived values of the eight coefficients of the Crohn’s Disease Activity Index (CDAI). Gastroenterology 1979;77(4 Pt 2): 843–846.Article PubMed
19. Best WR, Becktel JM, Singleton JW, Kern F Jr. Development of a Crohn’s Disease Activity Index: National Cooperative Crohn’s Disease Study. Gastroenterology 1976;70:439–444.Article PubMed
20. Lewis JD, Chuai S, Nessel L, Lichtenstein GR, Aberra FN, Ellenberg JH. Use of the noninvasive components of the Mayo score to assess clinical response in ulcerative colitis. Inflamm Bowel Dis 2008;14:1660–1666.Article PubMed PMC
21. Dashti HS, Scheer FA, Jacques PF, Lamon-Fava S, Ordovás JM. Short sleep duration and dietary intake: epidemiologic evidence, mechanisms, and health implications. Adv Nutr 2015;6:648–659.Article PubMed PMC
22. Cella D, Lai JS, Chang CH, Peterman A, Slavin M. Fatigue in cancer patients compared with fatigue in the general United States population. Cancer 2002;94:528–538.Article
23. Montan I, Löwe B, Cella D, Mehnert A, Hinz A. General population norms for the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale. Value Health 2018;21:1313–1321.Article
24. Lee HH, Gweon TG, Kang SG, Jung SH, Lee KM, Kang SB. Assessment of fatigue and associated factors in patients with inflammatory bowel disease: a questionnaire-based study. J Clin Med 2023;12:3116.Article PubMed PMC
25. Cohen BL, Zoëga H, Shah SA, et al. Fatigue is highly associated with poor health-related quality of life, disability and depression in newly-diagnosed patients with inflammatory bowel disease, independent of disease activity. Aliment Pharmacol Ther 2014;39:811–822.Article
26. Artom M, Czuber-Dochan W, Sturt J, Norton C. Targets for health interventions for inflammatory bowel disease-fatigue. J Crohns Colitis 2016;10:860–869.Article PubMed
27. Holten KI, Bernklev T, Opheim R, et al. Fatigue in patients with newly diagnosed inflammatory bowel disease: results from a prospective inception cohort, the IBSEN III Study. J Crohns Colitis 2023;17:1781–1790.Article PubMed PMC PDF
28. Graff LA, Vincent N, Walker JR, et al. A population-based study of fatigue and sleep difficulties in inflammatory bowel disease. Inflamm Bowel Dis 2011;17:1882–1889.Article PubMed
29. Ranjbaran Z, Keefer L, Farhadi A, Stepanski E, Sedghi S, Keshavarzian A. Impact of sleep disturbances in inflammatory bowel disease. J Gastroenterol Hepatol 2007;22:1748–1753.Article PubMed
30. Godala M, Gaszyńska E, Walczak K, Małecka-Wojciesko E. Evaluation of albumin, transferrin and transthyretin in inflammatory bowel disease patients as disease activity and nutritional status biomarkers. Nutrients 2023;15:3479.Article PubMed PMC
31. Lamers CR, de Roos NM, Heerink HH, van de Worp-Kalter LA, Witteman BJ. Lower impact of disease on daily life and less fatigue in patients with inflammatory bowel disease following a lifestyle intervention. Inflamm Bowel Dis 2022;28:1791–1799.Article PubMed PMC PDF
32. Grimstad T, Norheim KB, Isaksen K, et al. Fatigue in newly diagnosed inflammatory bowel disease. J Crohns Colitis 2015;9:725–730.Article PubMed
33. Paulides E, Cornelissen D, de Vries AC, van der Woude CJ. Inflammatory bowel disease negatively impacts household and family life. Frontline Gastroenterol 2021;13:402–408.Article PubMed PMC
34. Ezawa A. Family, inequality, and the work-family balance in contemporary Japan. In: Coates J, Fraser L, Pendleton M, editors. The Routledge Companion to Gender and Japanese Culture. 1st ed. London: Routledge, 2019:106-114.Article
35. Romberg-Camps MJ, Bol Y, Dagnelie PC, et al. Fatigue and health-related quality of life in inflammatory bowel disease: results from a population-based study in the Netherlands: the IBD-South Limburg cohort. Inflamm Bowel Dis 2010;16:2137–2147.PubMed
36. Graff LA, Clara I, Walker JR, et al. Changes in fatigue over 2 years are associated with activity of inflammatory bowel disease and psychological factors. Clin Gastroenterol Hepatol 2013;11:1140–1146.Article PubMed

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Understanding fatigue among Japanese patients with inflammatory bowel disease: insights from international comparisons and meta-analysis

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Understanding fatigue among Japanese patients with inflammatory bowel disease: insights from international comparisons and meta-analysis

Fig. 1. PRISMA 2020 flow diagram of study selection. PRISMA, Preferred Reporting Items for Systematic reviews and Meta-Analyses; FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue.

Fig. 2. Pooled mean FACIT-F (FS) score estimated by meta-analysis. FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; FS, Fatigue Subscale; SE, standard error; IV, interval variable; CI, confidence interval.

Fig. 3. Funnel plot of the mean FACIT-F (FS) score. FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; FS, Fatigue Subscale; SE, standard error.

Fig. 4. Subgroup analysis in patients with IBD in clinical remission: Pooled mean FACIT-F (FS) score estimated by meta-analysis. IBD, inflammatory bowel disease; FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; FS, Fatigue Subscale; SE, standard error; IV, interval variable; CI, confidence interval.

Fig. 1.

Fig. 2.

Fig. 3.

Fig. 4.

Understanding fatigue among Japanese patients with inflammatory bowel disease: insights from international comparisons and meta-analysis

Variable	UC (n = 204)	CD (n = 284)	Total (n = 488)	FACIT-F (FS)^a	Pearson r	P-value
Age (yr)	45.4 ± 14.3	42.0 ± 11.3	43.4 ± 12.7		–0.001	0.983
Sex (n = 487)						0.013
Male	111 (54.4)	209 (73.6)	320 (65.7)	40.6 ± 8.3
Female	93 (45.6)	74 (26.1)	167 (34.3)	38.5 ± 8.9
Diagnosis						0.669
UC	204 (100)	0	204 (41.8)	40.1 ± 7.9
CD	0	284 (100)	284 (58.2)	39.8 ± 9.1
Job status (n = 486)						0.001
No job	42 (20.6)	34 (12.0)	76 (15.6)	36.5 ± 9.7
Working or student	160 (78.4)	250 (88.0)	410 (84.4)	40.6 ± 8.2
Marital status (n = 487)						0.001
Single	76 (37.3)	125 (44.2)	201 (41.3)	38.3 ± 9.4
Married	128 (62.7)	158 (55.8)	286 (58.7)	41.0 ± 7.8
Disease duration (yr)	14.3 ± 8.2	17.5 ± 8.4	16.2 ± 8.5		–0.039	0.392
BMI (kg/m²)	22.2 ± 4.5	22.5 ± 3.5	22.4 ± 4.0		0.063	0.167
Disease phase (n = 483)						< 0.001
Remission	162 (79.4)	254 (91.0)	417 (86.3)	40.6 ± 8.2
Active	41 (20.1)	25 (9.0)	66 (13.7)	35.6 ± 9.6
Biologics						0.982
Presence	68 (33.3)	249 (87.7)	317 (65.0)	39.9 ± 8.9
Absence	136 (66.7)	35 (12.3)	171 (35.0)	39.9 ± 8.1
Sleep status						< 0.001
< 6 hr	50 (24.5)	85 (29.9)	135 (27.7)	37.0 ± 9.5
≥ 6 hr	154 (75.5)	199 (70.1)	353 (72.3)	41.0 ± 7.9
CRP level (mg/dL)	0.11 ± 0.29	0.23 ± 0.69	0.19 ± 0.58
Hemoglobin concentration (n = 434)						0.090
Low^b	19 (12.4)	59 (21.0)	74 (17.1)	38.4 ± 9.1
Normal range^c	134 (87.6)	222 (79.0)	360 (82.9)	40.3 ± 8.5
Albumin levels (n = 431)						< 0.001
< 3.8 g/dL	13 (8.7)	49 (17.4)	43 (10.0)	35.3 ± 12.2
≥ 3.8 g/dL	137 (91.3)	232 (82.6)	388 (90.0)	40.5 ± 8.1
Emotional Well-Being	18.0 ± 4.1	17.9 ± 4.5	18.0 ± 4.3		0.594	< 0.001

Factor	β	B (95% CI)	P-value
Female/male (ref)	–0.06	–1.09 (–2.67 to 0.51)	0.181
Working or student/no job (ref)	0.08	1.94 (–0.10 to 3.99)	0.062
Single/married (ref)	–0.08	–1.44 (–2.84 to –0.04)	0.044
CD/UC (ref)	–0.05	–0.84 (–2.33 to 0.65)	0.267
BMI	–0.02	–0.05 (–0.25 to 0.15)	0.614
Sleep time ≤ 6 hr/ > 6 hr (ref)	–0.11	–2.14 (–3.69 to –0.58)	0.007
Emotional Well-Being	0.51	1.05 (0.88 to 1.22)	< 0.001
Active disease/in remission (ref)	–0.08	–2.09 (–4.27 to 0.09)	0.060
Hemoglobin level low/normal range (ref)	0.01	0.18 (–1.77 to 2.14)	0.855
Albumin level low/normal range (ref)	–0.10	– 2.92 (–5.37 to –0.46)	0.020

Variable	Current study (2023)	Villoria et al. (2017) [12]	Williet et al. (2017) [13]	Tinsley et al. (2011) [11]	Saraiva et al. (2019) [14]	Tiankanon et al. (2021) [15]	Gatt et al. (2019) [16]	Stroie et al. (2023) [6]	Christensen et al. (2022) [17]
Country	Japan	Spain	France	USA	Portugal	Thailand	5 Countries^a	Romania	Denmark
Sample size	488	177	1,185	209	105	209	158	119	300
Age (yr)	43.4 ± 12.7	39.0 ± 12.0	45 (34–60)	38.6 ± 12.6	51.2 ± 15.8	47.3 ± 15.7	35.1 ± 12.8	39 (30–47)
Male sex (%)	66	58	39	47	43	49	51	61	54
Disease duration (yr)	16.2 ± 8.5	9.0 ± 6.0	14 (7–22)		13.4 (6.8–13.0)			6 (2–10)
BMI (kg/m²)	22.4 ± 4.0	25.0 ± 4.4	22.7 (20.4–25.6)
CD (%)	58	72	61	63	57	49	63	65	63
Active (%)	13.7	Few^b	62.9	16.7	Few^b	48.0	0	0
FACIT-F score^c
Overall	39.9 ± 8.6	38	30 (22–39)	38.9 ± 11.0	39.6 ± 9.7	40.9 ± 8.5	40.1 ± 12.2	41.6 ± 8.6	39
Overall	41 (35–47)
Remission	40.6 ± 8.2		36 (28–44)			42.5 ± 7.2	40.1 ± 12.2	41.6 ± 8.6
Remission	42 (36-47)
Active	35.6 ± 9.6					39.2 ± 9.4
Active	38 (31–42)
Male	40.6 ± 8.3	39.0 ± 11.0					41.1
Male	42 (36–47)
Female	38.5 ± 8.9	30 ± 13					39.0
Female	40 (34–45)
CD	39.8 ± 9.1	35.0 ± 12.0	30 (21–39)	38.6 ± 11.3			38.9 ± 12.2		39 (28–45)
CD	41 (35–47)
UC	40.1 ± 7.9	39 ± 11	31 (23–40)	39.4 ± 10.6			42.2 ± 12.0		40 (32–46)
UC	41 (36–46)

Table 1. Participants’ Backgrounds and Bivariate Analysis Results

Possible score range is (0–52), with higher scores indicating less fatigue impact.

Male (<13.5 g/dL), female (<11.3 g/dL).

Male (≥13.5 g/dL), female (≥11.3 g/dL).

UC, ulcerative colitis; CD, Crohn’s disease; FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; FS, Fatigue Subscale; BMI, body mass index; CRP, C-reactive protein.

Table 2. Factors Affecting the FACIT-F (FS) Score

R²=0.386, analysis of variance P<0.001.

Table 3. International Comparison of the Study Population and the Results of Fatigue in Inflammatory Bowel Disease Patients

Based on the values reported in each study, summary statistics for continuous variables are presented as mean±SD and/or median (IQR).

Greece, Cyprus, Malta, Hungary, and Israel.

Most patients were in clinical remission.

Possible score range is (0–52), with higher scores indicating less fatigue impact.

BMI, body mass index; CD, Crohn’s disease; FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; UC, ulcerative colitis; SD, standard deviation; IQR, interquartile range.