Fatigue is one of the most common and disabling symptoms experienced by people with inflammatory bowel disease; however, interventions to treat fatigue are limited. The purpose of this systematic review is to examine the relationship between sleep deficiency and fatigue in adults with inflammatory bowel disease and to describe the demographic and clinical factors associated with fatigue to inform future intervention work.

We conducted a systematic review and reported the results using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search was conducted using MEDLINE, EMBASE, PsycINFO, CINAHL, and CENTRAL on 3/7/24. We included studies with adults (≥18 years of age) who had a diagnosis of inflammatory bowel disease (Crohn's disease, ulcerative colitis, or indeterminate colitis) and measured fatigue and sleep using a validated self-report questionnaire or objective measurement.

Twenty-two studies met inclusion criteria for a total sample of 16 927, of whom 58.7% (n = 9937) had Crohn's disease, and 66.3% (n = 11 226) were female. 56.1% of the participants experienced fatigue and 66.3% experienced sleep deficiency. Sleep quality and insomnia were consistently associated with fatigue. Baseline poor sleep quality was associated with persistent and worsening fatigue over 12 to 24 months. Clinical but not objective assessment of disease activity, anxiety, depression, female gender/sex, and younger age were also associated with more severe fatigue.

Sleep quality and insomnia represent important modifiable contributors to fatigue. Future research should explore whether sleep interventions can improve fatigue in this population.

Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases (IBD) that have a negative impact on patient quality of life (QOL).

To evaluate QOL, work productivity, use of healthcare resources, and medical costs in patients with IBD from the RISE-MX trial.

RISE-MX was a non-interventional, multicentric, cross-sectional, retrospective study conducted in a Mexican population with IBD.

The 36-item Short Form Health Survey (SF-36) and the Inflammatory Bowel Disease Questionnaire (IBDQ) were used to assess QOL. The burden of disease was analyzed using the Work Productivity and Activity Impairment Questionnaire (WPAI), healthcare resources use, and medical costs.

Of 326 subjects, 95 (29.1%) had CD, and 231 (70.8%) had UC. In patients with CD, 43 patients (45.3%) showed moderate-to-severe activity, and 42 (18.1%) had moderate-to-severe disease activity in patients with UC. In all SF-36 dimensions, a significant difference between moderate-to-severe and mild activity/in remission groups was observed in patients with UC, while in patients with CD, the difference between activity groups was significant only for physical functioning and social functioning dimensions. In patients with CD, a higher but non-significant IBDQ score difference between activity groups was observed while a statistical difference between activity groups was observed for all dimensions in UC patients. In WPAI, the total percentage for work impairment (absenteeism plus presenteeism) and the percentage of regular daily activity impairment were statistically significant between activity groups only for UC. The annual total costs (direct and indirect) per patient in CD were USD 19,757 (moderate-to-severe activity group) and USD 12,587 (mild activity/in remission group), while in patients with UC were USD 11,702 and USD 9144, respectively.

Moderate-to-severe activity of disease was associated with a substantial impact on QOL, work productivity, and medical costs in Mexican patients with IBD. Total costs were higher for patients with CD than for patients with UC.

Inflammatory bowel disease (IBD) encompasses chronic inflammatory conditions of the digestive tract, including Crohn's disease and ulcerative colitis. Fatigue is one of the common and important extraintestinal symptoms in IBD patients, which significantly affects the patient's ability to work, daily life, social activities, emotional state, and cognitive function. Although the impact of fatigue on patients' quality of life cannot be ignored, medical professionals still have limited knowledge of its concepts, assessment tools, influencing factors, and non-pharmacological interventions, which may lead to neglect and inadequate management of the symptoms. The purpose of this article is to review the definition and epidemiological characteristics of IBD-related fatigue and to discuss the application of four commonly used fatigue assessment tools in patients with IBD. In addition, we will analyze the multiple factors that affect fatigue in IBD patients from three levels: physiological, psychological, and sociodemographic. Finally, we will assess the effectiveness of different non-pharmacological interventions in alleviating fatigue in people with IBD and make corresponding clinical recommendations.

To explore how rest is described or included as part of rest advice in fatigue interventions within rehabilitation for adults with Long-term conditions (LTC).

This scoping review identified fatigue interventions through PubMed, the Cumulative Index to Nursing and Allied Health Literature, the Allied and Complementary Medicine Database, and the Physiotherapy Evidence Database, from inception to July 2024.

Two independent reviewers screened and selected the articles. Studies were included if they: (1) involved adults with LTC, (2) used non-pharmacological fatigue interventions, (3) had fatigue as the primary outcome, and (4) were randomised controlled trials (5). Only randomised controlled trials that include rest advice in the interventions were selected.

Extracted data included the first author's name, year of publication, country, type of LTC, intervention category, specific interventions, how rest was reported in all interventions. Furthermore, rest was reported using the FITT principle, focusing on the frequency, intensity, duration, and type of rest in the exercise interventions and key conclusions.

Results were summarised, tabulated, and reported descriptively. Out of 13,645 initial records, 56 studies were included in the review. Of the total interventions analysed, 55.4% (31/56) were classified as physical activity interventions, 14.3% (8/56) as psychological interventions (e.g., cognitive behavioural therapy), 12.5% (7/56) were identified as energy management strategies, 8.9% (5/56) as educational interventions, and 8.9% (5/56) as activity pacing strategies. A disparity was observed in the instruction of rest advice between exercise interventions and daily fatigue management strategies. Specifically, physical activity interventions tended to adopt a more prescriptive approach to rest, whereas rest in daily fatigue management strategies was primarily instructed through education on the importance of rest in daily life. Notably, the level of detail provided in reporting rest parameters was generally limited.

This review found insufficient reporting of rest, highlighting a significant gap and indicating the need for improved documentation and standardisation of rest in fatigue interventions. Future research is necessary to better understand the role of rest in the rehabilitation of LTC.

Background/Aims: Numerous patients with ulcerative colitis (UC) become mentally unstable after experiencing a long-standing, physically painful life, and their long-term prognosis is poorer than that of those who are mentally stable. The current study aimed to evaluate serum biomarkers for predicting mental instability, which is challenging to objectively quantify. Methods: In total, 29 refractory UC patients newly treated with filgotinib underwent measurements of blood parameters associated with depression and a quantitative assessment of quality of life using the Inflammatory Bowel Disease Questionnaire (IBDQ) before and after treatment initiation with a 12-week interval. The data collected were examined in relation to each other. Results: The induction of remission treatment with filgotinib resulted in a clinical response rate of 89.7% and a clinical remission rate of 86.2%, with all eight extraintestinal manifestations resolved. No adverse events were observed. The serum zinc, high-density lipoprotein cholesterol, mature brain-derived neurotrophic factor (BDNF) concentrations, and the IBDQ psychiatric subscores increased significantly after treatment (p < 0.05). Among these parameters, the mature-BDNF concentration and the IBDQ psychiatric subscore had the strongest positive correlation (R = 0.29, p = 0.08). Based on the logistic regression analysis, the mature-BDNF concentration (cutoff value: 20.5 ng/mL) had a sensitivity of 68.2%, specificity of 64.7%, and area under the curve of 0.67 for predicting psychiatric remission (subscore > 42.5) (p = 0.04). Conclusions: While it is not easy to objectively predict the degree of psychiatric instability in patients with refractory UC, serum mature-BDNF levels can be a useful biomarker.

It is unclear what impact iron deficiency has on fatigue in people with inflammatory bowel disease (IBD). This systematic review examined the evidence of whether iron deficiency, with or without anaemia, was associated with fatigue in IBD. Fatigue is a common symptom in patients with IBD that can be difficult to manage and treat. A greater understanding of the role and contribution of iron deficiency to fatigue may help improve the management of this condition.

The databases searched were MEDLINE, OVID, CINAHL and Web of Science. Inclusion criteria were studies measuring iron status for iron deficiency (ID) and patient-reported outcome measures (PROMs) for fatigue in patients with IBD of any level of disease activity. Assessment of bias was conducted using the Newcastle Ottawa Scale. Studies were grouped for syntheses according to whether exposure was iron deficiency without anaemia (IDWA) or ID regardless of haemoglobin level.

Two hundred and eighty-five individual database results were identified and screened; 32 complete records were reviewed, from which seven studies with 1425 individuals were deemed eligible for inclusion in the results synthesis. Considerable variation in the methods and statistical analysis used to investigate the relationship between ID and fatigue prevented any quantitative synthesis. Studies varied by population disease activity levels, approaches used to define ID and PROMs used to measure fatigue. Three studies directly compared fatigue scores in IDWA to those not iron deficient, two of which showed patients with IDWA had significantly lower fatigue scores. Four studies used ID irrespective of anaemia as the exposure and reported mixed results on fatigue, with only one study reporting a higher prevalence of fatigue in the ID group.

There was marked heterogeneity between studies in this review. Two studies found evidence of a slight increase in fatigue levels in patients with IDWA. Though this does not explain all fatigue in patients with IBD, iron replacement should be considered to improve fatigue in iron-deficient patients.

A healthy lifestyle, including good adherence to a Mediterranean diet (MD) and regular physical exercise, may be an important factor during the course of inflammatory bowel disease (IBD). Our aim is to determine whether adherence to MD, physical activity, and the combination of both can impact on IBD course.

This prospective cohort study includes 693 IBD outpatients who were in remission with a median follow-up time of 27 months (interquartile range 22-29 months). Each patient completed a survey to assess their adherence to the MD and physical activity. Healthy lifestyle was considered to be a proper adherence to both MD and an active lifestyle. Relapse during follow-up, severity of relapses, need for systemic steroids, and therapy changes were recorded.

During the follow-up period, 188 patients (27.1%) experienced relapse, of which 56.1% were moderate or severe. Among patients with relapse, 85 (45%) required treatment with corticosteroids, and 15 (7.9%) were hospitalized. Patients with ulcerative colitis (CU) were more adherent to healthy lifestyle than patients with Crohn's disease (P = .011). Healthy lifestyle was associated with lower risk of moderate and severe relapses (adjusted Hazard ratio [aHR], 0.250; 95% confidence interval [CI], 0.093-0.670) and steroids use (aHR 0.292; 95% CI, 0.103-0.828) in IBD patients and with lower risk of moderate and severe relapses (aHR 0.270; 95% CI, 0.093-0.789) in UC patients.

Healthy lifestyle has a favorable influence on promoting a milder disease course, and thus should be a crucial part of clinical management of patients with IBD.

Ulcerative colitis (UC) and Crohn's disease (CD) are diseases that cause a significant impact on patients' quality of life. The aim of this study is to assess the impact of inflammatory bowel disease (IBD) on health-related quality of life (HRQoL).

Observational, descriptive, cross-sectional study, carried out at Torrecárdenas Hospital (Almería). Patients over 14 years of age diagnosed with CD or UC were included. For the assessment of HRQoL, the reduced 9-item IBDQ-9 questionnaire was used.

106 patients with a mean age of 44 years were included, with a female predominance. Forty-five percent of the patients in the sample had UC compared to 55% with CD. Of the patients, 69.8% were in clinical remission. The median questionnaire score was 60.8 points out of 100. Statistically significant differences were observed between sexes, with worse HRQoL for females. No differences were observed between patients with UC and CD. Differences were also detected between patients who underwent surgery and those who did not. A negative association was observed between the number of flares and the questionnaire score.

In our study population, there is an acceptable HRQoL, with no differences observed between CD and UC. Female sex, absence of clinical remission, number of previous outbreaks, and surgery have a negative association with HRQoL.

Fatigue is commonly reported in patients with Crohn's disease (CD) and ulcerative colitis (UC), including patients with inactive disease. We explored the impact of fatigue on healthcare utilization (HCU) and work productivity and activity impairment (WPAI).

Data collected between 2017 and 2022 were analyzed from the CorEvitas IBD Registry. We compared HCU and WPAI among subjects with high fatigue (PROMIS ≥55) versus low fatigue at enrollment and subjects whose fatigue score worsened or persisted versus low fatigue at 6 months. HCU was defined as an inflammatory bowel disease-related hospitalization or emergency room visit. WPAI included presenteeism, absenteeism, and lost WPAI. Logistic regression analysis was performed.

Study patients (640 CD, 569 UC) reported high rates of fatigue, 47% in CD and 38% in UC, that persisted at least 6 months in 88%-89% of patients. Patients with UC with high fatigue had 3-fold higher rates of HCU and 2-3-fold more absenteeism and activity impairment than patients with low fatigue. Patients with CD with high fatigue had no difference in HCU but did experience 2-4-fold more absenteeism, presenteeism, work productivity loss, and activity impairment. On subgroup analysis of patients in remission, those with high fatigue did not have higher rates of HCU but continued to have higher rates of WPAI.

Fatigue is associated with an increase in HCU only in the setting of concomitantly active disease. On the other hand, fatigue is associated with a negative impact on WPAI in the setting of both active and inactive disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and risk of malnutrition can coexist in patients with inflammatory bowel disease (IBD). We performed a malnutrition risk assessment as part of the standard follow-up of IBD patients and studied the potential risk factors for being at risk of malnutrition based on the presence or absence of MASLD.

The Malnutrition Universal Screening Tool (MUST) was used to screen malnutrition risk (MUST ≥1) and controlled attenuation parameter (CAP ≥248 dB/min) to assess MASLD. Adherence to a Mediterranean diet, physical activity, and quality of life were also assessed.

Of 686 evaluated IBD patients, 130 (18.9%) were identified as being at risk of malnutrition. Patients without MASLD (n = 89 [68.5%]) were more likely to be at risk than those with MASLD (n = 41 [31.5%], p = 0.005). However, among patients at risk of malnutrition, those with MASLD were more likely to have active IBD (82.9%) than patients without MASLD (39.3%, p < 0.001). Female sex (OR 1.984, p = 0.027) and young age (OR 1.014, p = 0.006) were associated with malnutrition risk only in patients with IBD without MASLD. Being at risk of malnutrition was associated with worse quality of life (p < 0.001), especially in IBD patients with MASLD.

Malnutrition risk and quality of life are modified by the presence of MASLD in IBD patients.

In recent years, there has been an observed increase in the global diagnosis rate of inflammatory bowel disease among children and adolescents. In inactive disease states, fatigue has emerged as the most debilitating symptom, while in active disease states, it ranks second. However, there remains a notable lack of understanding regarding fatigue in pediatric inflammatory bowel disease patients. Consequently, this study sought to investigate the prevalence and status of fatigue in a cohort of pediatric inflammatory bowel disease patients in China.

A cross-sectional, questionnaire-based survey was conducted. The researchers recruited 110 patients with inflammatory bowel disease using the convenient sampling method between 1 September 2021 until 31 November 2022 in Department of Gastroenterology of Children's Hospital of Nanjing Medical University. Fatigue was assessed using the Multidimensional Fatigue Scale, while potential factors associated with fatigue were analyzed through univariate and multiple regression analyses.

The study found that the total score of fatigue in children with inflammatory bowel disease was 62.22 ± 20.55. The univariate analysis revealed significant differences in the degree of fatigue across regions, ages, disease severities, corticosteroid use, and biological agent use. Furthermore, the multiple regression analysis indicated a significant difference in BMI (p < 0.05).

Fatigue is a multidimensional symptom that affects a majority of pediatric inflammatory bowel disease patients. Factors such as patient region, age, disease severity, BMI, and drug use are significantly associated with fatigue. Healthcare providers should prioritize the assessment of fatigue symptoms in these patients. Following the initial assessment, targeted interventions should be implemented to alleviate and improve these symptoms.

Fatigue is prevalent in patients with inflammatory bowel disease (IBD) in remission. Previously, we showed that fatigued IBD patients experienced a significant decrease in fatigue after receiving mindfulness-based cognitive therapy (MBCT). The current study examined to what extent these short-term beneficial effects of MBCT on fatigue were maintained over nine months follow-up, and whether patient characteristics were associated with clinically relevant improvement in fatigue.

A randomized controlled trial, including an MBCT and waiting-list control condition, was performed in fatigued IBD patients in remission. For this study, we analysed long-term outcomes of 108 patients who received MBCT (either directly or after three months waiting). The primary outcome was fatigue, assessed with the Checklist Individual Strenght-20. Secondary outcomes included fatigue interference, depression, anxiety, and quality of life.

The reduced level of fatigue post-treatment did not change significantly during follow-up (F(2,76) = 1.68, p = 0.19). In total, 29% of patients reported clinically relevant improvement from pre-treatment to nine months follow-up. We found few significant differences in baseline characteristics between those reporting clinically relevant improvement and those not, except that patients who improved were significantly more often unemployed (χ2(1, n = 73) = 4.40, p = 0.04). Secondary outcomes, which did not change significantly during MBCT, also remained stable during follow-up.

Findings suggest that reductions in IBD-related fatigue after receiving MBCT are sustained over nine months follow-up, with around one-third of patients reporting clinically relevant improvement from pre-treatment to follow-up. Employment status might be related to improvements in fatigue. Future research is needed to confirm these long-term outcomes.

ClinicalTrials.gov ID: NCT03162575.

Fatigue and psychosocial impairments are highly prevalent in IBD, particularly during active disease. Disturbed brain-gut interactions may contribute to these symptoms. This study examined associations between brain structure, faecal calprotectin, and symptoms of fatigue, depression, and anxiety in persons with Crohn's disease [CD] in different disease states.

In this prospective observational study, n = 109 participants [n = 67 persons with CD, n = 42 healthy controls] underwent cranial magnetic resonance imaging, provided stool samples for analysis of faecal calprotectin, and completed questionnaires to assess symptoms of fatigue, depression, and anxiety. We analysed differences in grey matter volume [GMV] between patients and controls, and associations between regional GMV alterations, neuropsychiatric symptoms, and faecal calprotectin.

Symptoms of fatigue, depression, and anxiety were increased in patients with CD compared with controls, with highest scores in active CD. Patients exhibited regionally reduced GMV in cortical and subcortical sensorimotor regions, occipitotemporal and medial frontal areas. Regional GMV differences showed a significant negative association with fatigue, but not with depression or anxiety. Subgroup analyses revealed symptom-GMV associations for fatigue in remitted but not in active CD, whereas fatigue was positively associated with faecal calprotectin in active but not in remitted disease.

Our findings support disturbed brain-gut interactions in CD which may be particularly relevant for fatigue during remitted disease. Reduced GMV in the precentral gyrus and other sensorimotor areas could reflect key contributions to fatigue pathophysiology in CD. A sensorimotor model of fatigue in CD could also pave the way for novel treatment approaches.

Ulcerative colitis (UC) is an inflammatory condition characterized by chronic, disabling gastrointestinal symptoms that can have detrimental effects on psychological, social, and professional quality of life. Few studies have examined patient-reported outcomes (PROs) and economic outcomes among individuals with varying UC severity and across different racial/ethnic groups.

This cross-sectional study assessed sociodemographic data, PROs, and economic outcomes for participants from the National Health and Wellness Survey (2018, 2019, and 2020) with UC. Multivariable analyses were used to assess the association of self-reported UC severity and race/ethnicity with health-related quality of life (HRQoL), work productivity and activity impairment (WPAI), healthcare resource utilization (HCRU), and medical costs.

This study included 1500 participants with UC (1150 non-Hispanic White, 99 non-Hispanic Black, and 251 Hispanic). Moderate/severe disease was associated with significantly worse HRQoL and WPAI, greater HCRU, and higher direct medical costs than mild UC. Compared with non-Hispanic White participants, non-Hispanic Black participants reported better HRQoL, whereas Hispanic participants reported more HCRU and higher medical costs. Race/ethnicity significantly interacted with UC severity level in predicting labor force participation.

Participants with moderate/severe disease had worse outcomes than those with mild UC. Additionally, racial/ethnic differences were found in HRQoL, employment, WPAI, HCRU, and direct medical costs. Notably, Hispanic participants showed distinct patterns, particularly in how disease severity influenced employment outcomes. Further research is needed to better understand the differential burden among patients across racial/ethnic groups.

Fatigue is common in people with inflammatory bowel disease (IBD) and is associated with IBD activity, sleep disturbance, anxiety and depression. The relative contribution of these factors to fatigue is unclear. This study aimed to investigate the relationship between fatigue and these factors through a novel approach using structural equation modelling.

Online questionnaire circulated via three tertiary IBD centres and Crohn's Colitis Australia.

Fatigue was assessed using the Functional assessment of chronic illness measurement system fatigue subscale. Validated measures of sleep, anxiety, depression and IBD activity were included. Following correlation analyses, a structural equation model was developed for the outcome of the fatigue score. Direct and indirect effects were calculated.

There were 630 complete responses to the online questionnaire. The median age of respondents was 41 with the majority female and over half (52%) on biologic medication. Structural equation models for Crohn's disease and ulcerative colitis demonstrated a good fit. In Crohn's disease, the relationship between IBD activity and fatigue was mostly mediated indirectly through the influence of IBD activity on sleep, anxiety and primarily depression. Sleep quality mediated the influence of IBD activity and the indirect effects of depression on fatigue, but not anxiety. Unlike in Crohn's disease, the direct influence of IBD activity on fatigue in ulcerative colitis was non-negligible, although remained of lesser magnitude than the indirect effect of IBD activity on fatigue. Depression was the primary indirect mediator of the influence of IBD activity on fatigue in ulcerative colitis.

In Crohn's disease, IBD activity leads to fatigue through its influence on sleep quality and mental health. The data suggest treatment of clinically significant depression, in both ulcerative colitis and Crohn's disease, may result in the largest decline in fatigue score compared to other variables. Treatment algorithms for fatigue should consider depression a priority.

A significant percentage of patients with an inflammatory bowel disease (IBD) encounter fatigue which can profoundly diminish patients' quality of life, particularly during periods of disease remission when gastrointestinal symptoms have receded. Various contributing risk factors have been identified including active inflammation, anemia, psychological, lifestyle and drug-related factors. While addressing these risk factors has been suggested as the initial approach to managing fatigue, a considerable number of patients still experience persisting symptoms, the primary causes of which remain incompletely understood. Recent insights suggest that dysfunction of the gut-brain axis may play a pathogenic role. This review provides an overview of established risk factors for fatigue, alongside emerging perspectives on the role of the gut-brain axis, and potential treatment strategies.

Psychological distress, especially depression, associated with perianal fistulizing Crohn's disease (PFCD) is widespread and refractory. However, there is a surprising paucity of studies to date that have sought to identify the prevalence and risk factors of depression associated with PFCD.

To estimate the prevalence of depressive symptoms and investigate the depression-related risk factors in patients with PFCD.

The study was conducted in the form of survey and clinical data collection via questionnaire and specialized medical staff. Depressive symptoms, life quality, and fatigue severity of patients with PFCD were assessed by Patient Health Questionnaire-9, Inflammatory Bowel Disease Patient Quality of Life Questionnaire (IBDQ), and Inflammatory Bowel Disease (IBD) Fatigue Patient Self-assessment Scale. The basic demographic information, overall disease features, perianal clinical information, and laboratory inflammation indicators were also gathered. Multivariate regression analysis was ultimately used to ascertain the risk factors of depression associated with PFCD.

A total of 123 patients with PFCD were involved, and 56.91% were suffering from depression. According to multivariate logistic regression analysis, Perianal Disease Activity Index (PDAI) score [odds ratio (OR) = 0.69, 95% confidence interval (CI): 0.50 to 0.95], IBDQ score (OR = 0.93, 95%CI: 0.88 to 0.97), modified Van Assche index (OR = 1.24, 95%CI: 1.01 to 1.53), and IBD Fatigue score (OR = 1.72, 95%CI: 1.23 to 2.42) were independent risk factors of depression-related prevalence among patients with PFCD (P < 0.05). Multiple linear regression analysis revealed that the increasing perianal modified Van Assche index (β value = 0.166, 95%CI: 0.02 to 0.31) and decreasing IBDQ score (β value = -0.116, 95%CI: -0.14 to -0.09) were independently associated with the severity of depression (P < 0.05).

Depressive symptoms in PFCD patients have significantly high prevalence. PDAI score, modified Van Assche index, quality of life, and fatigue severity were the main independent risk factors.

Fatigue is a complex and frequent symptom in persons with inflammatory bowel disease (IBD), with detrimental impact. We aimed to determine predictors of fatigue over time.

Two hundred forty-seven adults with IBD participated in a prospective study conducted in Manitoba, Canada, providing data at baseline and annually for 3 years. Participants reported fatigue impact (Daily Fatigue Impact Scale [DFIS]), depression and anxiety symptoms (Hospital Anxiety and Depression Scale [HADS]), and pain (Pain Effects Scale [PES]). Physician-diagnosed comorbidities, IBD characteristics, and physical and cognitive functioning were also assessed. We tested factors associated with fatigue using multivariable generalized linear models that estimated within-person and between-person effects.

Most participants were women (63.2%), White (85.4%), and had Crohn's disease (62%). At baseline, 27.9% reported moderate-severe fatigue impact, 16.7% had clinically elevated anxiety (HADS-A ≥11), and 6.5% had clinically elevated depression (HADS-D ≥11). Overall fatigue burden was stable over time, although approximately half the participants showed improved or worsening fatigue impact between annual visits during the study. On multivariable analysis, participants with a one-point higher HADS-D score had, on average, a 0.63-point higher DFIS score, whereas participants with a one-point higher PES score had a 0.78-point higher DFIS score. Within individuals, a one-point increase in HADS-D scores was associated with 0.61-point higher DFIS scores, in HADS-A scores with 0.23-point higher DFIS scores, and in PES scores with 0.38-point higher DFIS scores. No other variables predicted fatigue.

Anxiety, depression, and pain predicted fatigue impact over time in IBD, suggesting that targeting psychological factors and pain for intervention may lessen fatigue burden.

Fatigue is prevalent in people with inflammatory bowel disease (IBD) and has been associated with IBD activity, sleep quality, depression, and anxiety. This study aimed to identify fatigue profiles or clusters through latent profile analysis.

An online questionnaire was administered through three tertiary IBD centres, social media and through Crohn's Colitis Australia. Fatigue was assessed via the Functional assessment of chronic illness measurement system fatigue subscale (FACIT-F), a validated assessment of fatigue and its severity. Validated measures of anxiety, depression, IBD activity and sleep quality were also included. Latent profile analysis was performed including fatigue, sleep quality, active IBD, and depression and anxiety. The relationships between profiles and IBD and demographic data were investigated.

In a cohort of 535 respondents, 77% were female, the median age was 41 years (range 32-52 years), and the majority had Crohn's disease (62%). Severe fatigue was seen in 62%. Latent profile analysis identified four distinct profiles differing by fatigue score - low fatigue, at-risk profile, active IBD, and a poor mental health profile. Female gender, obesity and opioid usage were associated with higher risk of being in the active IBD and poor mental health profile. Age over 40 was associated with lower risk of being in the poor mental health profile.

Latent profile analysis identifies four classes of fatigue in an IBD cohort with associations with specific risk factors for fatigue along with specific IBD and demographic attributes. This has implications for the classification of fatigue in IBD and treatment algorithms.

Fatigue is a prominent symptom in many diseases and is strongly associated with impaired daily function. The measurement of daily function is currently almost always done with questionnaires, which are subjective and imprecise. With the recent advances of digital wearable technologies, novel approaches to evaluate daily function quantitatively and objectively in real-life conditions are increasingly possible. This also creates new possibilities to measure fatigue-related changes of daily function using such technologies.

This review examines which digitally assessable parameters in immune-mediated inflammatory and neurodegenerative diseases may have the greatest potential to reflect fatigue-related changes of daily function.

Results of a standardized analysis of the literature reporting about perception-, capacity-, and performance-evaluating assessment tools indicate that changes of the following parameters: physical activity, independence of daily living, social participation, working life, mental status, cognitive and aerobic capacity, and supervised and unsupervised mobility performance have the highest potential to reflect fatigue-related changes of daily function. These parameters thus hold the greatest potential for quantitatively measuring fatigue in representative diseases in real-life conditions, e.g., with digital wearable technologies. Furthermore, to the best of our knowledge, this is a new approach to analysing evidence for the design of performance-based digital assessment protocols in human research, which may stimulate further systematic research in this area.

The prevalence of depression is higher in patients with inflammatory bowel disease (IBD) than in the general population. Women are more significantly affected by depression among those with IBD and in the general population. This review presents evidence on sex-based differences in depression pathogenesis and the effect of depression on various factors associated with IBD that affect women's lives, including sexual dysfunction, body image dissatisfaction, fertility, and overall quality of life. We also discuss sex-specific effects on IBD treatment, disease activity, and health care costs. Interestingly, women with IBD tend to seek and are more receptive to depression-related information. Given the underdiagnosis and undertreated nature of depression in individuals with IBD, effective screening and an optimal integrative treatment approach with relevant sex-specific needs are discussed. Evidence regarding the efficacy of psychotherapy, antidepressant pharmacotherapy, and IBD-specific therapy for depression is discussed. This review summarizes evidence of the effect of depression on both personal and professional aspects of the daily lives of women with IBD, which extends beyond negative moods. It applies this information to screening and integrative treatment, resulting in a holistic approach to this multidimensional problem. We also discuss how depression affects males with IBD differently from females. Finally, we discuss the need for gender-based studies on depression in individuals with IBD.

Although fatigue is common in inflammatory bowel disease [IBD], its pathogenesis remains unclear. This study aimed to determine the prevalence of fatigue and its associated factors in a cohort of patients newly diagnosed with IBD.

Patients ≥18 years old were recruited from the Inflammatory Bowel Disease South-Eastern Norway [IBSEN III] study, a population-based, observational inception cohort. Fatigue was assessed using the Fatigue Questionnaire and compared with data from a Norwegian general population. Univariate and multivariate linear and logistic regression analyses were performed to evaluate the associations of total fatigue [TF; continuous score] and substantial fatigue [SF; dichotomized score ≥4] with sociodemographic, clinical, endoscopic, laboratory, and other relevant patient data.

In total, 983/1509 [65.1%] patients with complete fatigue data were included (ulcerative colitis [UC], 68.2%; Crohn's disease [CD], 31.8%). The prevalence of SF was higher in CD [69.6%] compared with UC [60.2%] [p < 0.01], and in both diagnoses when compared to the general population [p < 0.001]. In multivariate analyses, depressive symptoms, pain intensity, and sleep disturbances were associated with increased TF for both diagnoses. In addition, increased clinical disease activity and Mayo endoscopic score were significantly associated with TF in UC, whereas all disease-related variables were insignificant in CD. Similar findings were observed for SF, except regarding the Mayo endoscopic score.

SF affects approximately two-thirds of patients newly diagnosed with IBD. Fatigue was associated with depressive symptoms, sleep disturbances, and increased pain intensity in both diagnoses, while clinical and endoscopic activity were associated factors only in UC.

This post hoc analysis of a large, phase 3 program evaluated the effects of upadacitinib on fatigue, bowel urgency, and abdominal pain in patients with moderately to severely active ulcerative colitis.

Induction data were pooled from 2 identical studies, the U-ACHIEVE induction and U-ACCOMPLISH studies. Patients in these studies received upadacitinib 45 mg once daily or placebo as induction treatment. Responders to induction treatment were rerandomized in the U-ACHIEVE maintenance study to upadacitinib 15 mg once daily, upadacitinib 30 mg, or placebo. The percentage of patients reporting no abdominal pain and no bowel urgency daily via an electronic diary and a meaningful within-person change (≥5 points) in the Functional Assessment of Chronic Illness Therapy-Fatigue score were evaluated.

The results demonstrated a statistically significantly greater percentage of patients reporting no abdominal pain and absence of bowel urgency observed from week 2 (P < .001), with upadacitinib induction treatment and clinically meaningful improvements in Functional Assessment of Chronic Illness Therapy-Fatigue score observed at week 8 (P < .001), when compared with placebo. The maintenance study showed that significant and meaningful improvements in abdominal pain, bowel urgency, and Functional Assessment of Chronic Illness Therapy-Fatigue score achieved during induction were sustained through 52 weeks of maintenance treatment in upadacitinib- vs placebo-treated patients.

The findings of this study support the additional benefit of upadacitinib in treating moderately to severely active ulcerative colitis by demonstrating a statistically significant impact on clinically meaningful symptoms of fatigue, bowel urgency, and abdominal pain.(U-ACHIEVE induction and maintenance studies; NCT02819635; U-ACCOMPLISH induction study; NCT03653026).

Fatigue is a common symptom in children with inflammatory bowel disease (IBD). Diagnostic tests to evaluate biological causes of fatigue commonly include markers of inflammation and hemoglobin (Hb), yet functional parameters have been inadequately studied in pediatric IBD. In this study, we compared fatigued and non-fatigued children with IBD from both a biological and functional point of view.

A cross-sectional study of 104 pediatric IBD patients with mild to moderately active IBD was conducted. Fatigued children were defined as those with a Pediatric Quality of Life Inventory Multidimensional Fatigue Scale z score <-2.0. Non-fatigued children had a z score ≥-2.0. Disease-specific quality of life (measured with IMPACT-III score), C-reactive protein (CRP), fecal calprotectin (FC), hemoglobin z score (Hb z score), and physical activity tests including 6-minute walking distance z score (6MWD z score) and triaxial accelerometry (TA) were evaluated.

Fatigued children (n = 24) had a significant lower IMPACT-III score than non-fatigued children (n = 80). Hb z scores, CRP, FC, and 6MWD z scores were not significantly different between groups. TA was performed in 71 patients. Wear time validation requirements were met in only 31 patients. Fatigued patients spent significant shorter median time in moderate-to-vigorous activity than non-fatigued patients (18.3 vs 37.3 minutes per day, P = 0.008).

Biological parameters did not discriminate fatigued from non-fatigued patients. TA possibly distinguishes fatigued from non-fatigued patients; the potential association may provide a target for interventions to combat fatigue and improve quality of life.

Mild cognitive impairment (MCI) and Alzheimer's disease (AD) might be more frequent in patients with inflammatory bowel disease (IBD), but the relationship between these 2 entities is yet to be entirely established. Certain blood biomarkers (eg, serum amyloid A [SAA] and serum homocysteine [Hcy], which increase in IBD and MCI; brain-derived neurotrophic factor [BDNF], which decreases in MCI and AD but is not clearly modified in IBD; and S100 calcium-binding protein B [S100B], which increases in the blood-brain barrier and neuronal lesions) might predict the stage of MCI or dementia or progression to a further state. The gut-brain axis (GBA) might be the key to the development of MCI in patients with IBD, along with systemic inflammation and the possible and unknown adverse effects of disease-modifying medication.

The aim of this study is to investigate whether GBA interactions play a role in MCI development in patients with IBD.

A case-control study will be conducted on at least 100 patients diagnosed with IBD, matched with 100 healthy individual controls. The matching will include sex, age, and education. Patients will be fully examined, and a full interview and a neurological and cognitive examination will be performed. The primary clinical outcomes will be cognitive test scores (Montreal Cognitive Assessment, Trail Making Test, Digit Symbol Substitution Test, forward and backward digit span testing). Depression, stress, and anxiety screening will also be performed. Blood samples from all participants will be collected, and aliquots will be immediately stored in a biobank. Primary laboratory outcomes will include serum levels of presumed cognitive dysfunction blood biomarkers SAA, Hcy, S100B, and BDNF. Follow-up will be performed at 12, 24, 36, and 48 months.

Data collection started in December 2021 and is ongoing. So far, 53 patients with IBD have been recruited and 50 HC matched. Data collection should end in January 2030. Intermediary analysis will be performed in April 2024. We expect patients with IBD to have lower scores on cognitive testing and a positive correlation between disease length and cognitive impairment level. In addition, the levels of stress, anxiety, and depression should be higher in the IBD group. The serum levels of the 4 biomarkers could correlate or anticorrelate with cognitive scores and serve as predictive factors for MCI or dementia development. A higher level of education, a younger age, the absence of malabsorption, and good disease control might serve as protectors against MCI.

GBA interactions, along with systemic inflammation and the adverse effects of medication, might be a cause of MCI and AD development in patients with IBD. Serum biomarkers could prove cheap and useful predictors of MCI development.

ClinicalTrials.gov NCT05760729; https://clinicaltrials.gov/study/NCT05760729.

DERR1-10.2196/50546.

This study appraises the psychometrics properties of the Inflammatory bowel disease-fatigue (IBD-F) Persian version questionnaire.

The original IBD-F questionnaire was translated into the Persian version in a standard forward-back manner. The validation was performed through the face, content, and construct validity. Fifteen experts scored each item's necessity on an ordinal Likert scale of three; then, the content validity ratio was calculated using the Lawshe formula. Eight judges from pre-defined panel rated each item on an ordinal 4-point Likert scale concerning its relevancy, clarity, and simplicity for individual-CVI calculation. The mean individual-CVI was considered as the Scale-CVI for each domain. Twenty lay experts (selected from the target population) were asked to express their opinion on each item's importance by scoring on a 5-point Likert scale; subsequently, face validity was determined by the impact score formula. The questions that had minimum values of CVR, CVI, and impact score were retained in the final version of the questionnaire for reliability evaluation. Construct validity was evaluated via Confirmatory Factor Analysis. Internal consistency and test-retest reliability were checked using Cronbach's α and intraclass correlation coefficients (ICC). Fifty-four patients recruited based on inclusion and exclusion criteria to participate in the reliability analysis.

All the questions received the qualified values of CVR (exceeding 0.49 points) and impact score (more than 1.5 points) and were retained in the questionnaire; however, revisions were made for questions with a CVI 0.7-0.9 for clarity and simplicity. The result demonstrated relative goodness CFA and proper internal consistency, as Cronbach's α coefficient was 0.964 for the test (0.845 and 0.963 for the first and second part of the questionnaire, respectively (and 0.888 for the re-test (0.793 and 0.876 for the first and second section of the questionnaire, respectively). The ICC values between test and re-test for the first and second part and the whole questionnaire were obtained as 0.904, 0.922, and 0.921, respectively.

The Persian version of the IBD-F questionnaire was valid and reliable; thus, an appropriate scale was deemed to measure fatigue (severity, frequency, and impact on daily activities).

Fatigue has a detrimental impact on health-related quality of life and functioning in patients with Crohn's disease (CD). We aimed to confirm the relevance and importance of fatigue, establish the content validity of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), qualitatively explore meaningful change in fatigue experience, and assess the measurement properties of the FACIT-F in patients with moderate-to-severe CD.

This was a mixed-methods observational study consisting of a cross-sectional qualitative interview (Part A) and a longitudinal 2-week daily diary pilot study (Part B) in participants aged ≥ 18 years with a clinical diagnosis of moderate-to-severe CD. Part A included open-ended questions related to the participant's overall experiences with CD, fatigue, and impact on daily activities and a cognitive debriefing of several patient-reported outcomes (PROs), including the FACIT-F. Part B consisted of participants completing an electronic daily diary that included the FACIT-F and other PROs for 14 days. Item performance, test-retest reliability, and construct validity were assessed at baseline (Day 1), Day 7, and Day 14.

Thirty-five participants (mean age 45.1 years; 65.7% female) completed an interview (Part A). Ninety-one percent of the interview participants reported fatigue as a symptom attributed to CD. Participants indicated that fatigue had a major impact on their daily activities (e.g., recreation/ hobbies, work/school, yard work and housework), social activities, and emotional health. The FACIT-F was well understood by the interview participants. Seventy-six participants (mean age 41.9 years; 66% female) completed at least the Day 1 diary entry (Part B). Potential floor and ceiling effects were observed for several FACIT-F items, but test-retest reliability and construct validity were all strong and within the ranges hypothesized a priori.

The interviews indicate that fatigue is a frequent and bothersome symptom experienced by most patients with moderate-to-severe CD and support the content validity of the FACIT-F in this population. Daily diary study results indicate that the FACIT-F scale demonstrates adequate reliability and validity among patients with CD. These study findings suggest that the FACIT-F would be a reliable, valid, and useful measure of fatigue in patients with moderate-to-severe CD.

Although fatigue is common in patients with inflammatory bowel disease (IBD), it often goes unrecognized and untreated. We investigated the degree of fatigue and associated factors in patients with IBD. A multicenter study involving 147 IBD patients was conducted at five academic hospitals from August 2019 to December 2021. Fatigue was evaluated using the validated Korean version of the Multidimensional Fatigue Inventory (MFI-K). Among 97 ulcerative colitis patients and 50 Crohn's disease patients, the mean total MFI-K score was 59.0 ± 5.5, which corresponded to a moderate-to-severe level of fatigue. Moderate-to-severe disease activity was found to be significantly associated with a higher general and physical fatigue subscale MFI-K score compared to remission-to-mild disease activity (17.6 ± 1.7 vs. 16.7 ± 2.0, p = 0.009), while the use of biologics was associated with a lower total MFI-K score (57.3 ± 5.0 vs. 59.5 ± 5.5, p = 0.031). In multiple linear regression, the total MFI-K score was positively correlated with a history of surgery for IBD, while it was negatively correlated with the use of biologics. Depression was positively correlated with the reduced motivation subscale score. The degree of fatigue in patients with IBD was high. Disease activity, the use of biologics, a history of surgery for IBD, and depression were associated with fatigue.

Fatigue is a common problem in immune-mediated inflammatory disease (IMID) patients, significantly impacting their quality of life.

In this study, we describe the pattern and characteristics of fatigue as a patient-reported adverse drug reaction (ADR) of biologics, and compared patient and treatment characteristics with patients reporting other ADRs or no ADRs.

In this cohort event monitoring study, the description and characteristics of fatigue reported as a possible ADR in the Dutch Biologic Monitor were assessed and analysed for commonly recurring themes or patterns. Baseline and treatment characteristics of patients with fatigue and patients reporting other ADRs or no ADRs were compared.

Of 1382 participating patients, 108 patients (8%) reported fatigue as an ADR of a biologic. Almost half of these patients (50 patients, 46%) described episodes of fatigue during or shortly after biologic injection, which often recurred following subsequent injections. Patients with fatigue were significantly younger than patients with other ADRs or patients without ADRs (median age for patients with fatigue, 52 years; median age for patients with other ADRs, 56 years; and median age for patients without ADRs, 58 years); significantly more often smoked (25% vs. 16% and 15%); used infliximab (22% vs. 9% and 13%), rituximab (9% vs. 3% and 1%) or vedolizumab (6% vs. 2% and 1%); and significantly more often had Crohn's disease (28% vs. 13% and 13%) and other comorbidities (31% vs. 20% and 15%). Patients with fatigue significantly less frequently used etanercept (12% vs. 29% and 34%) or had rheumatoid arthritis (30% vs. 45% and 43%).

IMID patients may experience fatigue as a postdosing effect of biologics.

Anemia is a common extraintestinal manifestation of inflammatory bowel disease (IBD), with a 6% to 74% prevalence and a negative impact on patient survival and quality of life, although the prevalence is apparently declining due to improved disease treatment. We aimed to investigate the prevalence, pathogenesis, and clinical correlates of anemia in Italian patients with IBD.

A multicenter, prospective, observational study, involving 28 Italian gastroenterology centers, was conducted to investigate the epidemiology and consequences of IBD-associated anemia. Clinical and laboratory data of anemic patients were obtained at study enrolment.

Anemia was diagnosed in 737 of 5416 adult IBD outpatients (prevalence 13.6%); females were more commonly affected than males (odds ratio, 1.5; 95% confidence interval [CI], 1.2-1.7) and had more severe anemia. In the majority of cases, anemia was due to iron deficiency (62.5% of cases; 95% CI, 58.3%-66.6%), either isolated or in association with inflammation and/or vitamin deficiencies; anemia of inflammation accounted for only 8.3% of cases. More severe anemia was associated with increasing fatigue and worse quality of life. Only 68.9% of anemic patients with iron deficiency (95% CI, 63.4%-73.8%) and 34.6% of those with vitamin deficiencies (95% CI, 26.2%-44.2%) were properly treated with supplementation therapy.

In Italy, the prevalence of IBD-associated anemia is lower than previously reported. Anemia of IBD is most commonly due to iron deficiency and contributes to fatigue and poor quality of life, but remains untreated in a large proportion of patients with iron and/or vitamin deficiencies. This study is registered at clinicaltrials.gov as NCT02872376.

To assess the prevalence of fatigue and its association with disease activity and patient-reported outcomes among patients with ulcerative colitis (UC) or Crohn's disease (CD).

Data from a cross-sectional survey conducted with gastroenterologists and their consulting adult patients with UC or CD were analyzed. Data were collected via gastroenterologist-completed patient record forms and patient-self completion forms. Patient demographics, clinical characteristics, disease activity and medication use were reported by the gastroenterologist, while current symptoms (fatigue, rectal urgency, abdominal pain, sleep disturbance), work productivity and the Short Inflammatory Bowel Disease Questionnaire (SIBDQ) were reported by the patient. Logistic regression models were used to identify measures associated with fatigue and expressed as odds ratio (OR) with 95% confidence interval. p < 0.05 was considered statistically significant.

A total of 1057 patients with UC and 1228 patients with CD were included in this analysis. Fatigue was reported in 22.6% of UC and 26.0% of patients with CD. Higher proportion of patients with UC and fatigue had moderate/severe disease activity (p = 0.0001), had a higher Mayo score (5.0 vs. 4.0, p < 0.0001) and were unemployed (5.6% vs. 3.9%, p = 0.0149) compared to those without fatigue. In patients with CD reporting fatigue, a higher proportion were female (55.9% vs. 48.2%, p = 0.0193), were unemployed (5.8% vs. 4.9%, p = 0.0069), had moderate/severe disease (p < 0.0001) and had a higher mean Crohn's Disease Activity Index score (145.0 vs. 96.2, p < 0.0001) than patients without fatigue. Patients with UC and fatigue had higher mean level of pain (p < 0.0001) and sleep disturbance (p < 0.0001), whereas patients with CD and fatigue had lower SIBDQ scores (p < 0.0001) and greater work impairment (p = 0.0015) than patients without fatigue. Abdominal pain (OR: 2.01, p = 0.001) and use of immunomodulators (OR: 1.69, p = 0.006) increased the odds of having fatigue in patients with UC. In patients with CD, abdominal pain (OR: 2.29, p < 0.001) and use of biologics or biosimilars (OR: 2.02, p = 0.003) increased the odds of having fatigue.

Fatigue is a common symptom among patients with UC or CD that is associated with higher levels of disease activity and decreased work productivity and is driven by various factors. A multidisciplinary approach may be needed to manage fatigue.