Subtypes Of Fatigue Research Articles

Abstract P352: Association of General and Exertional Fatigue Subtype With Pre-Clinical Heart Failure Stage in Community Dwelling Older Adults in the Atherosclerosis Risk in Communities Study

Background: General and exertional fatigue are prevalent in heart failure (HF), can co-occur, and are associated with adverse outcomes. However, little is known about general and exertional fatigue in pre-clinical HF stages (stage A or B HF). Methods: In this cross-sectional analysis, we included participants at ARIC study visit 5 with stage A HF (risk factors for HF) or B HF (echocardiographic abnormalities or cardiac biomarker elevations). Using general fatigue (Patient Reported Outcomes Measurement Information System (PROMIS) fatigue scale) and exertional fatigue (Medical Research Council breathlessness scale) scores, we cross-categorized individuals into 4 fatigue subtypes: fatigue-free; high general fatigue only; high exertional fatigue only; high general/high exertional fatigue. The absence of a fatigue type was defined as a score of “none-mild”, and high severity as a score of “moderate-severe”. We examined the independent association of HF stage with fatigue subtype using multinomial logistic regression. Results: Our sample (N=4,269) was 59% female, 80% White, with a mean age of 75 years. Prevalence of any type of fatigue was 28% (n=1,179). Those with stage B had a higher prevalence of all fatigue types compared to stage A: high general fatigue only (10.2% vs 8.1%), high exertional fatigue only (12.6% vs 9.1%) and high general/high exertional fatigue (6.9% vs 4.7%). Compared to those with stage A, those with stage B had higher odds of having high general fatigue only (adjusted Odds Ratio (aOR) = 1.3 (95%CI = 1.0, 1.7)), high exertional fatigue only (aOR = 1.4 (1.1, 1.8)), and high general/high exertional fatigue (aOR = 1.6 (1.1, 2.2)) compared to being fatigue-free. Further adjustment for cardiometabolic risk factors attenuated these associations (Table). Conclusions: General and exertional fatigue are more prevalent in those with subclinical HF and these associations may be linked to cardiometabolic profiles. Prevention and management of risk factors may reduce the burden of fatigue in this population.

Fatigue is associated with disease severity in adult patients with hidradenitis suppurativa

AbstractBackgroundPatients with hidradenitis suppurativa (HS) experience fatigue, but no studies have yet examined the association between HS severity and fatigue intensity.ObjectivesTo examine the possible association between HS severity and fatigue and identify fatigue subtypes present in patients with HS.MethodsAdult patients with HS participated in a survey assessing fatigue using the Multidimensional Fatigue Inventory‐20. Disease severity was determined by self‐report.ResultsData from 654 adult patients with HS were analysed and compared with 3,788 reference individuals from the general population. Total and subtype fatigue scores for patients with HS were significantly higher compared with the general population reference individuals and increased with higher HS severity, itch, pain, sleep, dermatology life quality index scores and lower socioeconomic status. The association between HS severity and increased fatigue scores remained statistically significant after adjustment for age, sex, and socioeconomic status.ConclusionsPatients with HS had a significantly higher fatigue score compared with the general population reference individuals in a severity‐dependent manner. A higher awareness of fatigue as a symptom in patients with HS is warranted.

DEPRESSION MAY BE A STRONGER UNIQUE PREDICTOR OF FATIGUE THAN SELF-REPORTED IBD DISEASE ACTIVITY

Abstract Fatigue is a frequent and debilitating symptom of inflammatory bowel disease (IBD) and can include mental and physical exhaustion, tiredness, or weakness. Modifiable psychosocial factors, such as depression and anxiety, are associated with fatigue in IBD, and provide insight into potential treatment targets. However, little is known about distinct ways in which psychosocial factors relate to subtypes of fatigue. The current study examined associations between psychosocial factors and 5 fatigue subtypes: general, physical, mental, reduced motivation, and reduced activity. Patients 18 and above from Dartmouth-Hitchcock’s IBD Center with Crohn’s disease or ulcerative colitis were invited to participate in a survey via an electronic medical record system message. Measures included the Patient Reported Outcomes-3, Multidimensional Fatigue Inventory, Pain Catastrophizing Scale, Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, Insomnia Severity Index, and Brief Pain Inventory. Five forward linear regressions were performed with step 1 including disease activity, step 2 including covariates (age, gender, IBD diagnosis) and step 3 allowing for the inclusion of insomnia, pain severity, depression, anxiety, and pain catastrophizing. Participants were 312 individuals above the age of 18 (M=48.62, SD=16.10). Participants were 66.3% women and 96.5% White. 60.9% were diagnosed with Crohn’s disease and 39.1% with ulcerative colitis. 54.8% were categorized as having active disease based on self-reported symptoms. For all five subtypes of fatigue, depression emerged as the most influential psychosocial predictor. Depression accounted for 21% of the variance in general fatigue, 14% in physical fatigue, 18% in activity avoidance, 19% in reduced motivation, and 29% in mental fatigue. Regarding differences among subtypes, insomnia was only significant in the model predicting general fatigue, accounting for an additional 2% of the variance, and anxiety was only significant in the model predicting activity avoidance, accounting for an additional 3% of the variance. In comparison, self-reported disease activity accounted for 23% of the variance in general fatigue, 7% in physical fatigue, 8% in activity avoidance, 12% in reduced motivation, and 10% in mental fatigue. Depression is a notable factor associated with all subtypes of fatigue in IBD, especially mental fatigue. There are differences in how psychosocial factors relate to fatigue subtypes such that anxiety is uniquely associated with activity avoidance and severity of insomnia is uniquely associated with general fatigue. Results suggest that assessment of fatigue in IBD should also include assessment of depression as standard of care. Additionally, helping patients engage in behavioral interventions to reduce depression, anxiety, and insomnia may be critical for managing fatigue. Results of forward regressions predicting fatigue subtypes

Identification of Fatigue Subtypes and Their Correlates in Prevalent Heart Failure: A Secondary Analysis of the Atherosclerosis Risk in Communities Study.

Among patients with heart failure (HF), fatigue is common and linked to quality of life and functional status. Fatigue is hypothesized to manifest as multiple types, with general and exertional components. Unique subtypes of fatigue in HF may require differential assessment and treatment to improve outcomes. We conducted this study to identify fatigue subtypes in persons with prevalent HF in the ARIC study (Atherosclerosis Risk in Communities) and describe the distribution of characteristics across subtypes. We performed a cross-sectional analysis of 1065 participants with prevalent HF at ARIC visit 5 (2011-2013). We measured exertional fatigue using the Modified Medical Research Council Breathlessness scale and general fatigue using the Patient Reported Outcomes Measurement Information System fatigue scale. We used latent class analysis to identify subtypes of fatigue. Number of classes was determined using model fit statistics, and classes were interpreted and assigned fatigue severity rating based on the conditional probability of endorsing survey items given class. We compared characteristics across classes using multinomial regression. Overall, participants were 54% female and 38% Black with a mean age of 77. We identified 4 latent classes (fatigue subtypes): (1) high general/high exertional fatigue (18%), (2) high general/low exertional fatigue (27%), (3) moderate general/moderate exertional fatigue (20%), and (4) low/no general and exertional fatigue (35%). Female sex, Black race, lower education level, higher body mass index, increased depressive symptoms, and higher prevalence of diabetes were associated with higher levels of general and exertional fatigue. We identified unique subtypes of fatigue in patients with HF who have not been previously described. Within subtype, general and exertional fatigue were mostly concordant in severity, and exertional fatigue only occurred in conjunction with general fatigue, not alone. Further understanding these fatigue types and their relationships to outcomes may enhance our understanding of the symptom experience and inform prognostication and secondary prevention efforts for persons with HF.

Cancer-related fatigue: Towards a more targeted approach based on classification by biomarkers and psychological factors.

Cancer-related fatigue is a frequent, burdensome and often insufficiently treated symptom. A more targeted treatment of fatigue is urgently needed. Therefore, we examined biomarkers and clinical factors to identify fatigue subtypes with potentially different pathophysiologies. The study population comprised disease-free breast cancer survivors of a German population-based case-control study who were re-assessed on average 6 (FU1, n = 1871) and 11 years (FU2, n = 1295) after diagnosis. At FU1 and FU2, we assessed fatigue with the 20-item multidimensional Fatigue Assessment Questionnaire and further factors by structured telephone-interviews. Serum samples collected at FU1 were analyzed for IL-1ß, IL-2, IL-4, IL-6, IL-10, TNF-a, GM-CSF, IL-5, VEGF-A, SAA, CRP, VCAM-1, ICAM-1, leptin, adiponectin and resistin. Exploratory cluster analyses among survivors with fatigue at FU1 and no history of depression yielded three clusters (CL1, CL2 and CL3). CL1 (n = 195) on average had high levels of TNF-α, IL1-β, IL-6, resistin, VEGF-A and GM-CSF, and showed high BMI and pain levels. Fatigue in CL1 manifested rather in physical dimensions. Contrarily, CL2 (n = 78) was characterized by high leptin level and had highest cognitive fatigue. CL3 (n = 318) did not show any prominent characteristics. Fatigued survivors with a history of depression (n = 214) had significantly higher physical, emotional and cognitive fatigue and showed significantly less amelioration of fatigue from FU1 to FU2 than survivors without depression. In conclusion, from the broad phenotype "cancer-related fatigue" we were able to delineate subgroups characterized by biomarkers or history of depression. Future investigations may take these subtypes into account, ultimately enabling a better targeted therapy of fatigue.

Abstract 17809: Association of Fatigue Subtype With Echocardiographic Measures of Cardiac Structure and Function in Prevalent HF in the Atherosclerosis Risk in Communities Study

Background: Fatigue is prevalent in heart failure (HF) patients and strongly linked to adverse outcomes, but the relationship of cardiac structure and function with fatigue type and severity in HF is unknown. Methods: We included 947 individuals with prevalent HF from visit 5 (2011-2013) of the ARIC study with data on general and exertional fatigue, and echocardiographic measures. We previously identified four subtypes of fatigue using latent class analysis: Low/no fatigue, high general/low exertional, moderate general/moderate exertional, and high general/high exertional fatigue. We used multinomial logistic regression to determine the relationship between 1-SD higher echocardiographic parameters and fatigue subtypes, adjusting for age and sex. Results: Our sample was 54% female and 38% Black, with mean age of 77 ± 5.5 and LVEF of 61% ± 10. Adjusting for sex and age, worse longitudinal strain (OR = 1.55 [1.13, 2.13]), higher LV mass index (OR = 1.62 [1.23, 2.14]), and multiple measures of impaired diastolic function were associated with higher odds of having the high general/high exertional fatigue subtype compared to the low/no fatigue subtype (Table) . LV mass index and impaired diastolic function were also associated with higher odds of having the moderate general/moderate exertional fatigue subtype (Table) . Adjustment for additional sociodemographic and clinical characteristics attenuated associations, with only lateral E/e` significantly associated with the high general/high exertional fatigue subtype (OR= 1.81 [1.12, 2.91]), and the moderate general/moderate exertional fatigue subtype (OR=1.44 [1.10, 1.96]). Conclusions: Associations of fatigue subtype with cardiac structure and function are largely explained by other sociodemographic and clinical characteristics. Supplementary interventions targeting non-cardiac structural and functional mechanisms of fatigue may contribute to improved fatigue symptomatology in prevalent HF.

JS03.7.A INTERPLAY BETWEEN SELF-REPORTED AND PERFORMANCE-BASED SYMPTOMS IN PATIENTS WITH GLIOMA AND MENINGIOMA - A NETWORK ANALYSIS AND COMPARISON BETWEEN DIAGNOSES

Abstract BACKGROUND Patients with brain tumors show complex symptomatology often involving self-reported complaints, e.g., concerning self-perceived cognitive function (SCF), fatigue or mood, as well as deficits in cognitive performance. Understanding the interplay between symptoms across diagnoses is crucial for intervention, but remains challenging. This study used network analysis to 1) uncover unique relationships between various multidimensional self-reported symptoms and cognitive performances in patients with meningioma and glioma, and 2) investigate differences in symptom networks between diagnoses. MATERIAL AND METHODS We used pre-surgical data from patients with meningioma (n=240) and glioma (n=208). Two Gaussian graphical models were constructed to explore conditional relationships among symptoms in the two samples. Included as symptoms in the networks were ten patient-reported measures: SCF (3 nodes), Anxiety, Depression, and Fatigue (5 nodes), and 5 cognitive performance measures: Inhibition, Cognitive flexibility, Verbal memory, Processing speed and Psychomotor speed. We evaluated the importance of the symptoms with three centrality indices; node strength, betweenness and closeness. We compared features of the networks between the diagnoses with a Network Comparison Test. RESULTS In both samples, particularly strong connections existed between Anxiety and Depression, Forgetfulness and False Triggering (SCF nodes), and General Fatigue and Physical Fatigue. These positive relationships were significantly stronger than most of the other relationships. The most central symptoms, based on the strength of their connections with other symptoms, were Forgetfulness, General Fatigue and Inhibition in glioma patients, and Forgetfulness, Physical Fatigue and Depression in meningioma patients. Activity-related fatigue appeared as the least central symptom in the glioma network, but it was in the top 5 in the meningioma network. The difference in the number of relationships found (meningioma: 49 vs. glioma: 41), was not significant. Visual inspection of the networks suggested additional connections between multiple fatigue and cognition nodes in meningioma that were absent in glioma. Significant differences were found between the networks regarding strength of the relationships General Fatigue-Physical Fatigue (stronger in glioma), and Physical Fatigue-Activity-related Fatigue (stronger in meningioma), p’s < .01. CONCLUSION While symptom networks of patients with glioma and meningioma show similarities, they appear to differ with regard to which symptoms play a more central role and how strongly some symptoms are related. Particularly fatigue subtypes may carry different importance. Information that multidimensional symptom networks provide about how symptoms interact can guide treatment decisions for patients with different diagnoses.

The Association Between Fatigue and Adult Atopic Dermatitis: A Cross-Sectional Study.

Background: There is currently limited insight into the broader impact of atopic dermatitis (AD) on mental health. Although studies indicate that AD patients may experience fatigue, no study has so far examined fatigue in more granular detail, for example, occurrence of general fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue, or correlated fatigue measures with AD severity and symptoms intensity. Objectives: To examine fatigue subtypes and their prevalence in adults with AD, as well as their possible association with AD severity. Methods: A survey was conducted in adults with AD who had been managed in a hospital setting. The Patient-Oriented SCORing Atopic Dermatitis was used to determine AD severity. Patient reported outcomes, including multidimensional fatigue inventory, were included. Results: Data from 2729 adults with AD were analyzed. The total and individual fatigue scores increased consistently with lower socioeconomic scores, higher AD severity, Dermatology Life Quality Index, itch, pain, and sleep scores. Increased fatigue scores were associated with AD severity in adjusted analyses. Conclusions: Among adults with AD, fatigue scores increased with disease severity as well as intensity of AD symptoms. Fatigue is a hitherto underappreciated symptom of AD that clinicians should be cognizant about.

Abstract 12099: Relationship Between Fatigue Subtype and Heart Failure Admission, Quality of Life, and Mortality in Persons With Heart Failure: A Secondary Analysis of the Atherosclerosis Risk in Communities Study

Introduction Fatigue is one of the most common and distressing symptoms of heart failure (HF). It consists of two types: general and exertional. Although it’s common, little is known about whether and which type of fatigue is associated with patient reported and clinical outcomes. We conducted a secondary data analysis of the Atherosclerosis Risk in Communities (ARIC) study to determine if fatigue type predicts key patient reported and clinical outcomes in persons with HF. Methods This analysis included 1,068 individuals with a diagnosis of prevalent HF at visit 5 (2011-2013) of the ARIC study with available survey data on general and exertional fatigue. Four fatigue subtypes were identified previously through latent class analysis on general and exertional fatigue survey items in this sample. These fatigue subtypes are: 1) High general & exertional, 2) High general & low exertional, 3) Moderate general & exertional, and 4) Low/No fatigue (reference category). To assess the relationship between fatigue subtype and outcomes, we used latent class regression, regressing HF hospitalization, quality of life (QOL, SF-12 scale) and mortality on fatigue subtype, adjusting for covariates (demographics, clinical comorbidities, and medications). Results Our sample was 54% female and 38% Black, with a mean age of 77 ± 5.5. Those with the high general & exertional fatigue subtype had 2.2 times higher likelihood of HF hospitalization than those with the low/no fatigue subtype (OR = 2.2; 95%CI = 1.2, 4.1). Those with the high general & exertional fatigue subtype had significantly poorer mean physical (50.3 v 64.6, p<0.001) and mental (49.3 v 58.0, p<0.001) QOL than those with the low/no fatigue subtype. Those with the moderate general & exertional fatigue subtype also had significantly poorer physical QOL than the low/no fatigue subtype (61.9 v 64.6, p<0.001). There were no significant differences in mortality between fatigue subtypes. Conclusions Fatigue subtype in persons with HF is associated with HF admissions and quality of life. It will be important to elucidate the pathways underlying the development of fatigue and to determine whether targeting fatigue can improve clinical outcomes.

Characterizing Fatigue Subtypes in Adolescents with Chronic Musculoskeletal Pain and Pain-Free Controls.

ContextGeneral fatigue, sleep-related fatigue, and cognitive fatigue are prevalent and disruptive in adults with chronic musculoskeletal (MSK) pain, but little is known about these fatigue subtypes in pediatric musculoskeletal pain.ObjectiveTo compare fatigue and its subtypes between adolescents with chronic MSK pain and pain-free controls and to test if fatigue subtypes were associated with concurrent pain and its impact (pain intensity, number of pain sites, pain interference, and functional disability) or experimental pain (intensity and tolerance) in adolescents with chronic MSK pain. Finally, we sought to explore adolescents’ qualitative characterizations of their fatigue.MethodsAdolescents with chronic MSK pain (12–17 y.o., n = 26) and pain-free controls (n = 26) completed validated self-report measures of fatigue, pain, and functional disability, underwent an experimental pain tolerance task (cold water immersion of the hand), and provided qualitative descriptions of their fatigue (pain group only).ResultsAdolescents with chronic MSK pain reported significantly greater general, sleep-related, and cognitive fatigue than pain-free controls (all p’s < 0.001). In adolescents with chronic MSK pain, fatigue subtypes were associated with clinical pain and pain impact (r’s = 0.43–0.84) but not experimental pain measures (p’s > 0.05). Adolescents with chronic MSK pain qualitatively described the negative implications of the different fatigue subtypes, particularly when perceived as long-lasting.ConclusionThis preliminary study suggests that fatigue subtypes are prevalent and impactful in pediatric patients with chronic MSK pain. When planning multi-disciplinary treatment for pediatric MSK pain, providers should recognize fatigue as another disabling symptom.

Abstract 80: Subtypes Of Fatigue In Heart Failure In The Atherosclerosis Risk In Communities Study

Background: Heart failure (HF) affects ~6 million people in the US and is associated with marked morbidity and adverse clinical outcomes. Among HF patients, fatigue is common and distressing symptoms that significantly impacts patient quality of life and function. Current literature primarily examines fatigue as a single and generalized symptom. Fatigue is hypothesized, however, to manifest as multiple types, with both general and exertional components. Unique subtypes of fatigue in HF may require differential assessment and treatment to improve patient-reported and clinical outcomes. Objective: To identify unique fatigue subtypes in persons with prevalent HF in the Atherosclerosis Risk in Communities (ARIC) study. Methods: We performed a cross-sectional analysis of 1,114 participants at Visit 5 (2011-13) of the ARIC study with prevalent HF. We used the Modified Medical Research Council Breathlessness scale obtained at Visit 5 to assess exertional fatigue, and the PROMIS fatigue scale obtained at the 1 st semi-annual follow up after Visit 5 (2012-2014) to assess general fatigue. We used latent class analysis to identify unique subtypes of fatigue based on patterns of responses to each of the scales. Results: Participants were 54% female and 38% Black with a mean age of 77 ± 5.5. We identified four latent classes of fatigue symptoms: 1) low/no fatigue, 2) high exertional &amp; moderate general fatigue, 3) high general &amp; low exertional fatigue, and 4) high general &amp; exertional fatigue. The low/no fatigue class was the largest with an estimated 35.2% of the sample. The high exertional &amp; moderate general class and the high general &amp; low exertional class had similar estimated prevalences (23.5% and 23.8%, respectively). The high general &amp; high exertional class was the smallest with an estimated 17.4% prevalence. Conclusions: We identified unique subtypes of fatigue in HF patients that have not been previously described in the literature. Future studies should examine the relationship between these latent classes of fatigue type and important patient-reported and clinical HF outcomes. Understanding these fatigue types and their relationships to outcomes may enhance our understanding of the symptom experience and inform prognostication in patients with HF.

Cross-Sectional Associations of Fatigue Subtypes with Pain Interference in Younger, Middle-Aged, and Older Adults with Chronic Orofacial Pain.

Mental, emotional, physical, and general fatigue, as well as vigor, have each been associated with pain interference-defined as pain-related disruption of social, recreational, and work-related activities-in patients with chronic orofacial pain (COFP). The objectives of the current study were to compare levels of these fatigue subtypes across younger, middle-aged, and older patients with COFP and test the associations between fatigue subtypes and pain interference in these age groups. A cross-sectional cohort design was used. Participants self-reported fatigue subtypes (Multidimensional Fatigue Symptom Inventory-Short Form), pain interference (West Haven-Yale Multidimensional Pain Inventory), pain intensity (visual analog scale), pain duration (months), depression (Symptom Checklist 90-Revised), and sleep quality (Pittsburgh Sleep Quality Index) at their initial appointment at a tertiary orofacial pain clinic. Sixty younger (age 18-39), 134 middle-aged (age 40-59), and 51 older (age 60-79) COFP patients provided data for the study. Analysis of variance was used to compare levels of fatigue subtypes between the age groups. Regression with dummy-coding was used to test if the relationship between fatigue subtypes and pain interference varied by age. Older COFP patients reported less general fatigue and more vigor than younger or middle-aged adults. Fatigue subtypes were each associated with greater pain interference, but associations became nonsignificant after controlling for depression, sleep, and pain intensity/duration. Age group-by-fatigue subtype interactions were not observed. Managing fatigue may be important to reduce pain interference in COFP populations and may be accomplished in part by improving depression and sleep.

Experiences of fatigue in daily life of people with acquired brain injury: a qualitative study

Purpose To develop an in-depth understanding of how survivors of acquired brain injury (ABI) experience fatigue and how fatigue affects everyday life. Materials and methods We conducted semi-structured in-depth interviews with 16 adults with ABI fatigue, recruited from support groups in south east UK. Interviews were analysed using the frameworks method. Results We developed four themes: experiencing fatigue in the context of everyday activities, struggling to make sense of fatigue, coping with fatigue, and adjusting social participation in the context of fatigue. Fatigue was comprised of mental, physical, generalised, and motivational fatigue. Balancing fatigue against participation in daily activities was influenced by coping strategies and social support. Opportunities to socialize or participate in meaningful activities provided incentives for participants to push through their fatigue. Conclusions This study highlights complex interactions that potentially mitigate the impact of fatigue on everyday life. Educational and self-management approaches to fatigue need to account for different types of fatigue in the contexts of an individual’s daily activity. Assessment of fatigue should capture in-the-moment experiences of different types of fatigue and activity. Social support and participation in meaningful activities may help individuals to break the negative cycle of fatigue and inactivity. Implications for rehabilitation Assessment of fatigue after brain injury should capture the multidimensional nature of fatigue as well as contextual information about exacerbating activities and environments. Development of personalised coping strategies that account for perceived triggers of different subtypes of fatigue may help ABI survivors to broaden their activity and social participation. Social support and opportunities to participate in personally meaningful activities may help prevent or break a negative cycle of fatigue and inactivity for some ABI survivors.

In search of distinct MS-related fatigue subtypes: results from a multi-cohort analysis in 1.403 MS patients.

Fatigue is among the most disabling symptoms in patients with multiple sclerosis (PwMS). The common distinction between cognitive and motor fatigue is typically incorporated in self-rating instruments, such as the Chalder Fatigue Questionnaire (CFQ), the Fatigue Scale for Motor and Cognitive Functions (FSMC) or the Modified Fatigue Impact Scale (MFIS). The present study investigated the factor structure of the CFQ, the FSMC and the MFIS utilizing exploratory (EFA) and confirmatory factor analysis (CFA) as well as exploratory structural equation modeling (ESEM). Data of 1.403 PwMS were analyzed, utilizing four samples. The first sample (N = 605) was assessed online and split into two stratified halves to perform EFA, CFA, and ESEM on the CFQ and FSMC. The second sample (N = 293) was another online sample. It served to calculate CFA and ESEM on the CFQ and FSMC. The third sample was gathered in a clinical setting (N = 196) and analyzed by applying CFA and ESEM to the FSMC. The fourth sample (N = 309) was assessed in a clinical setting and allowed to run a CFA and ESEM on the MFIS. Proposed factor structures of all questionnaires were largely confirmed in EFA. However, none of the calculated CFAs and ESEMs could verify the proposed factor structures of the three measures, even with oblique rotation techniques. The findings might have implications for future research into the pathophysiological basis of MS-related fatigue and could affect the suitability of such measures as outcomes for treatment trials, presumably targeting specific sub-components of fatigue.

Treating Fatigue in Rheumatoid Arthritis: Does Patient Age Matter?

Clinically relevant fatigue is common in patients with rheumatoid arthritis (RA) and might be expected to be related to patient age and disease severity. This review provides a brief introduction to fatigue as a patient-reported outcome that contributes significantly to burden of disease, with a focus on the evidence in elderly patients, and gives an overview of our current understanding of the factors that contribute to fatigue. We summarize the evidence for the effects of pharmacological (disease-modifying anti-rheumatic drugs, DMARDs) and non-pharmacological interventions for fatigue. The underlying pathophysiology of fatigue is complex and often multifactorial. The experience of fatigue varies between individuals, and subtypes of fatigue are increasingly being recognized. Fatigue can therefore be challenging to recognize and quantify. Recent systematic reviews have shown that fatigue can be improved as a result of treatment with traditional and biological anti-rheumatic drugs, and also with non-pharmacological approaches (physical activity, psychosocial interventions). Age does not appear to be of major importance for fatigue in RA, and similar strategies for treating fatigue apply to all age groups, including the elderly.

Identification and Validation of Clinically Relevant Clusters of Severe Fatigue in Rheumatoid Arthritis.

The considerable heterogeneity of rheumatoid arthritis (RA)-related fatigue is the greatest challenge to determining pathogenesis. The identification of homogenous subtypes of severe fatigue would inform the design and analysis of experiments seeking to characterize the likely numerous causal pathways that underpin the symptom. This study aimed to identify and validate such fatigue subtypes in patients with RA. Data were obtained from patients recruited to the British Society for Rheumatology Biologics register for RA, as either receiving traditional disease-modifying antirheumatic drugs (DMARD cohort, n = 522) or commencing anti-tumor necrosis factor therapy (anti-TNF cohort, n = 3909). In those reporting severe fatigue (Short-Form 36 vitality ≤ 12.5), this cross-sectional analysis applied hierarchical clustering with weighted-average linkage identified clusters of pain, fatigue, mental health (all Short-Form 36), disability (Health Assessment Questionnaire), and inflammation (erythrocyte sedimentation rate) in the DMARD cohort. K-means clustering sought to validate the solution in the anti-TNF cohort. Clusters were characterized using a priori generated symptom definitions and between-cluster comparisons. Four severe fatigue clusters, labeled as basic (46%), affective (40%), inflammatory (4.5%), and global (8.9%) were identified in the DMARD cohort. All clusters had severe levels of pain and disability and were distinguished by the presence/absence of poor mental health and high inflammation. The same symptom clusters were present in the anti-TNF cohort, although the proportion of participants in each cluster differed (basic = 28.7%; affective = 30.2%; global = 24.1%; inflammatory = 16.9%). Among RA patients with severe fatigue, recruited to two diverse RA cohorts, clinically relevant clusters were identified and validated. These may provide the basis for future mechanistic studies and ultimately support a stratified approach to fatigue management.

P 133 Differentiating hypo- and hyperaroused fatigue in major depression and in the context of organic diseases

Introduction Fatigue is a core symptom in patients with major depressive disorder (MDD), and a common symptom in organic diseases involving inflammatory and immunological processes. From a clinical perspective, fatigue in depression is a state with high inner tension and prolonged sleep onset latencies, whereas fatigue in the context of organic diseases describes an anergic state with excessive sleepiness and short sleep latencies. Given that these two states are diametrically opposed in the arousal dimension, it has been proposed to differentiate two subtypes of fatigue ( Hegerl et al., 2013 , Hegerl and Ulke, 2016 ): hyperaroused fatigue (typical for depression) and hypoaroused fatigue (typical in the context of organic diseases). Due to the striking heterogeneity of MDD and frequent occurrence of depressive symptoms in organic diseases, we sought to examine whether both fatigue subtypes can be found within a sample of depressed patients (study 1) and within a sample of subjects with inflammatory-immunological diseases and cancer (study 2). In the first study, we hypothesized that in MDD fatigue with unstable arousal regulation is associated with higher sleepiness scores and more atypical symptoms (e.g. short sleep onset latency) than fatigue with stable arousal regulation. In the second study, we hypothesized that in the context of organic diseases fatigue with stable arousal regulation is associated with higher depression and lower sleepiness scores than fatigue with labile arousal regulation. Methods Sample Study 1: MDD-Patients with clinically relevant fatigue (N = 102). Sample Study 2: Subjects with clinically relevant fatigue in the context of inflammatory-immunological diseases and cancer (N = 127). Arousal regulation was assessed based on 20-min resting-EEG using automatic EEG-vigilance stage classification with the Vigilance Algorithm Leipzig (VIGALL 2.1). Subjects were separated into groups according to their arousal regulation. Results Study 1: According to our hypothesis, fatigue subtypes in the context of MDD differ in regard to daytime sleepiness (ESS: p Conclusions An unstable arousal regulation in MDD-Patients with clinically relevant fatigue could influence the treatment strategy. Stable arousal regulation in persons with clinically relevant fatigue in the context of organic diseases can be an indication of a comorbid depression, which has to be treated according to guidelines.

All Fatigue is Not Created Equal: The Association of Fatigue and Its Subtypes on Pain Interference in Orofacial Pain.

Fatigue is known to be a pathway through which depression, psychological distress, pain intensity, and sleep disturbance influence pain interference, but the independent effects of fatigue on pain interference after controlling for these variables remains unknown. In addition, no study to date has tested whether fatigue subtypes of general fatigue, mental fatigue, emotional fatigue, physical fatigue, or vigor differentially predict pain interference. The current study tested these associations using archival medical data of 2133 chronic orofacial pain patients, who completed a battery of psychological questionnaires at the time of their first appointment at an orofacial pain clinic. Hierarchical linear regression analysis revealed that after controlling for depression, psychological distress, sleep disturbance, pain intensity, and demographic variables, fatigue predicted higher pain interference (B=0.70, SE=0.17, P<0.001, η=0.01). Physical fatigue (B=1.70, SE=0.48, P<0.001, η=0.01) and vigor (B=-3.24, SE=0.47, P<0.001, η=0.03) were independently associated with pain interference after controlling for the aforementioned variables. The findings suggest that fatigue is an important independent predictor of pain interference and not merely a mediator. These findings also suggest that not all fatigue is created equal. Interventions aimed at reducing pain interference should target specific fatigue symptoms of physical fatigue and vigor. Future research investigating the independent associations of fatigue subtypes on pain outcomes may help clarify the nature of the interrelationships between pain and fatigue.

Fatigue Mediates the Relationship Between Pain Interference and Distress in Patients with Persistent Orofacial Pain

To test the role of fatigue and its subtypes (general, physical, emotional, mental, and vigor) in mediating the relationship between psychological distress and pain interference. Retrospective, de-identified records were examined for 431 patients seeking treatment for persistent orofacial pain. Primary diagnoses of participants were muscle pain (29.8%), joint pain (26.0%), neuropathic pain (19.5%), and other (ie, fibromyalgia, centrally mediated myalgia, tendonitis, dental pain, cervical spine displacement, and no diagnosis; 24.7%). Mediation models were tested with distress as the independent variable, interference as the dependent variable, and fatigue or its subtypes as the mediators. After controlling for pain duration and average levels of pain, total fatigue mediated the relationship between distress and interference. Fatigue subtypes partially mediated the relationship between distress and interference, but mediation was strongest with the composite fatigue variable. The results, however, should be interpreted cautiously, as data were collected at a single time point and do not imply causality. These results suggest that interventions targeted specifically at fatigue symptoms may be helpful for reducing interference and improving quality of life in patients with persistent orofacial pain.

Fatigue assessment of Parkinson’s disease patient in clinic: specific versus holistic

Fatigue is a frequently encountered non-motor symptom in Parkinson's disease (PD). Being a subjective definition, with no biological markers, it is difficult to describe. Its definition is influenced by the background and culture of the patient. Subtypes of fatigue are peripheral fatigue and mental fatigue. The co-existence of other non-motor symptoms in PD complicates its assessment. Fatigue could be present before, at the time of diagnosis of PD in untreated patients or during the course of the disease. Scales that can be used for evaluation include generic one for a holistic manner and those specifically designed for PD. A scale designed for fatigue should differentiate between PD patients with fatigue and those without fatigue. The next step is to choose between unidimensional which evaluate one dimension and multidimensional scales. We present the main scales which can be used for fatigue assessment and their properties. The scales are presented with some psychometric properties in non-PD population and those properties through validation in PD population. Scales have some properties which could be recommended for screening and/or rating of severity of fatigue in PD.