Severity Of Fatigue Symptoms Research Articles

Longitudinal Fatigue Symptoms and Inflammatory Markers in African American Adults With Hypertension and Obstructive Sleep Apnea.

There is a dearth of research inclusive of African Americans living with obstructive sleep apnea (OSA) despite differences in symptom presentations compared to non-Hispanic White patient populations. Less is known regarding the potential effect of comorbidities, such as hypertension, on commonly reported symptoms, such as fatigue, and their association with inflammatory biomarkers. This longitudinal pilot study aimed to characterize fatigue symptom presentations among African Americans newly diagnosed with OSA and discern peripheral blood analytes linked to symptoms while accounting for co-occurring hypertension. Adult African Americans newly diagnosed with OSA with and without co-occurring hypertension were approached by study staff and recruited following their diagnostic visit with sleep medicine clinicians at two health systems and followed over 6 months after commencing continuous positive airway pressure treatment. Patient-Reported Outcomes Measurement Information System Fatigue surveys and plasma were collected every 3 months from 29 participants. Mixed effects models examined changes in fatigue symptom presentations over time while accounting for plasma-based analytes and hypertension status. Despite higher fatigue symptom severity upon diagnosis, participants with co-occurring hypertension reported greater improvements in fatigue scores after commencing continuous positive airway pressure treatment for up to 6 months than those without hypertension. Inverse correlations were observed between fatigue scores, C-reactive protein, matrix-metalloproteinase-8, and osteoprotegerin analyte levels among participants with/without hypertension. Across all participants, changes in interleukin-6 were associated with changes in fatigue scores in the first three months after diagnosis. Findings indicate that hypertension is linked to increased fatigue upon diagnosis of OSA in this sample of African Americans. Fatigue in persons with hypertension improved after treatment. These hypothesis-generating findings can inform future interventional studies aimed at improving fatigue among persons with OSA while leveraging markers linked to fatigue symptom severity as potential objective markers of improvements. Further research on the role of inflammatory markers, such as IL-6, on fatigue symptom presentations is warranted in those with OSA regardless of hypertension status.

Assessing Variability in Reporting Severity of the Same Symptom (Fatigue) in the Context of Different Psychiatric Syndromes.

Objective The objective of this study is to examine the variability in the self-reported fatigue symptom severity in major depressive disorder (MDD) compared to generalized anxiety disorder (GAD). Methods A retrospective chart review was conducted of 100 patients evaluated for fatigue using depression and anxiety questionnaires. The study examined whether ratings of fatigue varied based on whether fatigue was being rated by the patient in the context of MDD vs. when fatigue was being rated by the same patient in the context of GAD. A related-sampleWilcoxon signed-rank test and Mann-Whitney U test were used to compare the median differences between depression and anxiety fatigue scores. The significance level used was 0.05. Results This study found a statistically significant difference in the median difference of the paired depression fatigue and anxiety fatigue scores (depression score - anxiety score) regardless of the order of administration (Wilcoxon signed-rank test statistic = 135.500, p-value =.008, N = 100 paired scores). Conclusion The study's conclusions show that although the symptom of fatigue is listed in the Diagnostic Statistical Manual 5 (DSM-5) criteria for MDD as well as GAD, it may be perceived by patients differently based on the context of the syndrome. This emphasizes the importance of considering the context of symptom reporting in patients with MDD and GAD to improve diagnostic methodologies and treatment strategies.

Chronotype and the Big-Five personality traits as predictors of chronic fatigue among patients with sarcoidosis. A cross-sectional study.

Sarcoidosis may seriously hamper patients' quality of life despite fairly good prognosis. To assess the relationship between the Big Five personality traits, chronotype and severity of fatigue symptoms, in the context of selected clinical variables and general mental health among patients with sarcoidosis. The study group comprised 60 patients with a confirmed diagnosis of sarcoidosis. They were asked to share relevant clinical data and complete a set of questionnaires: Fatigue Asessment Scale (FAS), General Health Questionnaire (GHQ-28), the NEO Five Factor Inventory and Composite Scale of Morningness. In linear regression analysis, FAS score was predicted by female sex, active sarcoidosis status, Morning Affect and Conscientiousness. In principal component analysis, FAS score and all GHQ-28 subscale scores (somatic symptoms, anxiety/insomnia, social dysfunction and depressive symptoms) formed a single component explaining 60% of variance. The factor loading for each variable exceeded 0.6. The psychological burden appeared to rise with the severity of the fatigue, regardless the inactive/active phase of sarcoidosis. The severity of fatigue may be linked to patient's poor morning affect. The profile of psychological burden presented by the patients may be associated with their personality and clinical presentation of sarcoidosis.

Predictors of patient-reported fatigue symptom severity in a nationwide multiple sclerosis cohort.

Fatigue is a debilitating symptom of multiple sclerosis (MS), but its relation to sociodemographic and disease-related characteristics has not been investigated in larger studies. The objectives of this study were to evaluate predictors of self-reported fatigue in a Swedish nationwide register-based MS cohort. Using a repeated cross-sectional design, we included 2,165 persons with relapsing- remitting and secondary progressive MS with one or multiple Fatigue Scale for Motor and Cognitive Functions (FSMC) scores, which was modelled using multivariable linear regressions for multiple predictors. Only associations to expanded disability status scale (EDSS) and Symbol Digit Modalities Test (SDMT) were considered clinically meaningful among MS-associated characteristics in our main model; compared to mild disability (EDSS 0-2.5), those with severe disability (EDSS ≥6) scored 17.6 (95% CI 13.1-22.2) FSMC points higher, while the difference was 10.7 (95% CI 8.0-13.4) points for the highest and lowest quartiles of SDMT. Differences between highest and lowest quartiles of health-related quality of life (HRQoL) instruments were even greater and considered clinically meaningful; EuroQoL Visual Analogue Scale (EQ-VAS) 31.9 (95% CI 29.9-33.8), Multiple Sclerosis Impact Scale (MSIS-29) psychological component 35.6 (95% CI 33.8-37.4) and MSIS-29 physical component 45.5 (95% CI 43.7-47.4). Higher self-reported fatigue is associated with higher disability level and worse cognitive processing speed, while associations to other MS-associated characteristics including MS type, line of disease modifying therapy (DMT), MS duration, relapse and new cerebral lesions are weak. Furthermore, we found a strong correlation between high fatigue rating and lower ratings on health-related quality of life instruments.

The Link between the Demographic and Clinical Factors and Fatigue Symptoms among Rheumatoid Arthritis Patients.

Rheumatoid arthritis (RA) is a chronic systemic disease of connective tissue with periods of exacerbation and remission. Fatigue is excessive strain throughout the body that is disproportionate or unrelated to an activity or lifestyle. Fatigue is an integral part of RA in most patients. The study aimed to assess the level of fatigue in RA patients and establish the relationship between fatigue and demographic and clinical factors. The study group consisted of 128 RA patients according to European League Against Rheumatism (EULAR) criteria. The Functional Assessment of Chronic Illness Therapy-Fatigue and -Medical Outcomes Study Short Form 36 (SF-36) vitality scores were used to assess the severity of fatigue symptoms. The analyzed variables were gender, age, disease duration, education, marital status, place of residence, work and residence status, pharmacological treatment, pain, morning stiffness, hemoglobin, C-reactive protein (CRP), rheumatoid factor (RF), compression soreness, Richie Articular Index, and DAS28 disease activity. The examined patients experience chronic fatigue-the mean value on the FACIT-F scale was 24.1 ± 9.1 points and on the SF-36 Vitality score was 14.2 ± 1.8 points. There is a relationship between the level of fatigue and pain, long-lasting morning stiffness, active disease, increased soreness of joints, and low hemoglobin values. When analyzing the symptom of fatigue, each patient should be approached individually, using the existing questionnaires or asking key questions to recognize the situation. The presence of fatigue symptoms should be considered during therapy and patient care by searching for and eliminating additional, intensifying stimuli and increasing its level.

Prospective Associations of Susceptibility-Weighted Imaging Biomarkers with Fatigue Symptom Severity in Childhood Traumatic Brain Injury.

Fatigue may be among the most profound and debilitating consequences of pediatric traumatic brain injury (TBI); however, neurostructural risk factors associated with post-injury fatigue remain elusive. This prospective study aimed to evaluate the independent value of susceptibility-weighted imaging (SWI) biomarkers, over-and-above known risk factors, to predict fatigue symptom severity in children with TBI. Forty-two children were examined with structural magnetic resonance imaging (sMRI), including a SWI sequence, within eight weeks post-injury. The PedsQL Multi-Dimensional Fatigue Scale (MFS) was administered 24 months post-injury. Compared with population expectations, the TBI group displayed significantly higher levels of general fatigue (Cohen d = 0.44), cognitive fatigue (Cohen d = 0.59), sleep/rest fatigue (Cohen d = 0.37), and total fatigue (Cohen d = 0.63). In multi-variate models adjusted for TBI severity, child demographic factors, and depression, we found that subacute volume of SWI lesions was independently associated with all fatigue symptom domains. The magnitude of the brain-behavior relationship varied by fatigue symptom domain, such that the strongest relationships were observed for the cognitive fatigue and total fatigue symptom scales. Overall, we found that total subacute volume of SWI lesions explained up to 24% additional variance in multi-dimensional fatigue, over-and-above known risk factors. The subacute SWI has potential to improve prediction of post-injury fatigue in children with TBI. Our preliminary findings suggest that volume of SWI lesions may represent a novel, independent biomarker of post-injury fatigue, which could help to identify high-risk children who are likely to benefit from targeted psychoeducation and/or preventive strategies to minimize risk of long-term post-injury fatigue.

Association between sleep health and cognitive reserve in older adults with cognitive concerns

AbstractBackgroundWe examined the association between sleep health consequences and perceived fatigability within the context of carrying out everyday activities in non‐demented older adults and investigated whether cognitive reserve (CR; individual differences in susceptibility to cognitive decline due to brain aging, pathology, or insult) moderated this relationship.MethodThis was a cross‐sectional study. We prospectively screened adults age 55‐90 years at a Memory Research Clinic. An IRB approved the study protocol, and informed consent was obtained. Patients with cognitive concerns underwent neurocognitive testing to determine cognitive status based on the ADNI criteria. Inclusion criteria: the ADNI criteria for cognitively normal or MCI. Exclusion criteria: 1) depression assessed with the Geriatric Depression Scale (GDS>5) and DSM‐5 criteria, 2) history of primary psychiatric illnesses, 3) medical conditions associated with fatigue, and 4) a history of obstructive sleep apnea diagnosed by a clinical sleep physician. Measures included the PROMIS Sleep‐related Impairment (SRI); the Neuro‐QOL Cognitive function (CogF) and Fatigue measure, which yields “fatigue symptom severity (Fat_Sx)” and “perceived fatigability (Fatiga)” subscales. CR was assessed with the CR Index questionnaire (CRIq). Linear regression models were fit to the fatigue outcomes and included the SRI, CR, and their interaction as predictors. If the interaction was significant, SRI slopes were assessed at CR=mean and mean ±1SD. All analyses were adjusted for age, sex, and education.ResultThere were 37 subjects in this study; mean age of 70.8 years (SD=9.3); 70.3% subjects were female; 86.5% white, 10.8% Hispanic, and 2.7% others. CR significantly moderated the relationship between SRI and perceived fatigability (F (1,32)=18.64, p=0.011). A higher SRI score was associated with a higher perceived fatigability severity with a low CR (CRIq mean‐1SD)=108.6; b(se)=.493(.089), p<0.001) and a mean CR (CRIq mean=128.0; b(se)=.274(.076); p=0.001), but not a high CR (CRIg mean+1SD=147.4; b(se)=0.1278; p=0.636). Moreover, higher perceived fatigability was associated with lower cognitive function (b(se)=‐.24 2(0.077), p=0.004), controlling for age, gender, and education.ConclusionPoorer cognitive function was significantly associated with greater fatigability within the context of managing everyday activities. Greater cognitive reserve may reduce the detrimental influence of poor sleep health on perceived fatigability in managing daily function during the preclinical stages of dementia.

Patient-reported functional outcomes 30 days after hospitalization for COVID-19.

BackgroundMany coronavirus disease 2019 (COVID‐19) survivors experience persistent symptoms, such as fatigue, dyspnea, and musculoskeletal pain. However, less is known about the impact of COVID‐19 on longer term functional outcomes.ObjectiveTo evaluate patient‐reported activity of daily living (ADL) function and fatigue symptoms 30 days after hospitalization for COVID‐19.DesignCross‐sectional study.SettingTertiary care university hospital.ParticipantsAdults 18 years or older hospitalized for COVID‐19 and survived to 30 days after discharge.MethodsA standardized telephone questionnaire was administered 30 days after hospital discharge.Main Outcome MeasuresAbility to perform basic and instrumental ADLs and fatigue symptoms severity (Patient‐Reported Outcome Measurement Information System [PROMIS] Fatigue Short Form 7a) were assessed by self‐report.ResultsParticipants (n = 55) were 22‐95 years old. Compared to pre‐COVID hospitalization, 52% developed new difficulty and 6% new dependence with performing basic ADLs (bADLs), 48% developed new difficulty and 11% new dependence with instrumental ADLs (iADLs), and 69% experienced a clinically significant worsening in their fatigue symptom severity. The average fatigue symptom severity T‐score before hospitalization was 44.2 ± 7.4 and after hospitalization was 54.5 ± 9.8. In exploratory multivariate analyses, each additional COVID symptom at presentation was associated with a predicted increase of 1.43 units (95% confidence interval [CI], 0.45–2.42) in the 30‐day fatigue symptom severity T‐score, each additional day of hospitalization was associated with an 1.2 times increased odds of worsening fatigue (95% CI, 0.98–1.5; p = .08), and each unit increase in baseline body mass index was associated with 0.8 times decreased odds of new bADL or iADL dependence at 30 days (95% CI, 0.65–0.99).ConclusionsNew functional impairments are common at 30 days after discharge among survivors of hospitalization for COVID‐19. Early rehabilitation, advance care planning, and referrals to appropriate therapies should be considered in postacute COVID‐19 care to maximize patients' functional outcomes. However, ongoing research is still needed regarding management of these patients.

Sleep increases leaks and asynchronies during home noninvasive ventilation: a polysomnographic study.

In patients treated with noninvasive ventilation, sleep-related breathing changes can modify patient-ventilator interactions, which could reduce its effectiveness. The aim of this prospective observational study was to determine the impact of sleep/wake state on leaks, upper airway obstructive events, and asynchronies in patients treated by long-term noninvasive ventilation. Stable patients adapted to noninvasive ventilation were considered for nocturnal polysomnography. Unintentional leaks, upper airway obstructive events, and asynchronies were compared between sleep and awake periods. Twenty-eight patients were enrolled. Underlying diagnoses were neuromuscular disease (n = 11), chest wall disease (n = 8), and obesity-hypoventilation (n = 9). Leaks were more frequent in sleep than in awake periods, with a median of 10% (interquartile range [IQR], 0%-75%) vs 1% (IQR, 0%-9%) of time (P < .001), respectively. During sleep, asynchronies with and without associated leak affected 27% of breaths (IQR, 16%-39%) compared with non-leak-related asynchronies that were recorded in 8% (IQR, 3%-25%) of breaths (P < .001). Asynchronies affecting more than 10% of total breaths were more frequent in sleep (25 patients, 89%) than in awake time (8 patients, 29%; P = .25). Eleven patients (39%) presented with 5 or more upper airway obstructive events without reduction in ventilatory drive per hour of sleep. In patients adapted to home noninvasive ventilation, leaks, asynchronies, and upper airway obstructive events are frequent during the night and are concentrated in sleep periods. Asynchronies are often associated with leaks. These findings may have clinical implications considering that in patients with low sleep efficiency respiratory events could be underestimated if sleep is not evaluated. Martí S, Ferré A, Sampol G, etal. Sleep increases leaks and asynchronies during home noninvasive ventilation: a polysomnographic study. J Clin Sleep Med. 2022;18(1):225-233.

Inflammation and Fatigue in Patients with Cold Agglutinin Disease (CAD): Analysis from the Phase 3 Cardinal Study

Introduction CAD is a rare, chronic type of autoimmune hemolytic anemia, where hemolysis is driven by classical complement pathway (CP) activation. Complement activation assures rapid initiation of the complement cascade as part of an early immune response and inflammation. A proinflammatory state secondary to complement activation has been demonstrated in other hemolytic disease such as paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome (Weitz et al. Thromb Res. 2012; Cofiell et al. Blood. 2015). Complement activation stimulates cytokine production (tumor necrosis factor, interleukin 6 [IL-6], IL-8, IL-17) via anaphylatoxins C3a and C5a and increases vascular inflammatory markers, consistent with complement-mediated inflammation (Landsem et al. Clin Exp Immunol. 2017; Cofiell et al. Blood. 2015). In patients with chronic fatigue syndrome, complement activation is associated with higher levels of fatigue (Sorensen et al. J Allergy Clin Immunol. 2003) and inflammatory cytokine activity correlates with the severity of fatigue symptoms (Montoya et al. PNAS. 2017). In addition, IL-6 plays a more dominant role in immune stimulation, particularly during chronic inflammation stress such as rheumatoid arthritis (Choy et al. Rheumatology. 2018). In CAD, CP activation and chronic inflammation may contribute to patient fatigue, apart from anemia. CP activation resulting in a proinflammatory state has not been formally studied in CAD. The interplay between complement-mediated inflammation and fatigue also has not been previously explored in patients with CAD. In the Cardinal study (NCT03347396), efficacy and safety of the humanized monoclonal anti-C1s antibody, sutimlimab (formerly BIVV009), was evaluated in patients with CAD and recent history of blood transfusion. Here we summarize the results of inflammatory cytokine expression for IL-6 and IL-10 and their relation to fatigue over the Part A 26-week treatment period of Cardinal. Methods In Cardinal Part A, patients with CAD received intravenous doses of sutimlimab on Days 0 and 7, and biweekly infusions thereafter. Patients weighing &amp;lt;75 kg and ≥75 kg received a 6.5 g and 7.5 g dose, respectively. Cytokine levels for IL-6 and IL-10 were assessed in patients with available serum samples. Cytokine profiles and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scores were evaluated from baseline to follow-up time points at Weeks 1, 3, 5, and 25, as represented by the treatment assessment time point (TAT) after initiating sutimlimab treatment. Summary statistics describing IL-6, IL-10, and FACIT-F changes at each week were reported. Results Mean IL-6 level (mean pg/mL [standard error of the mean (SEM)]) steadily decreased from baseline (3.21 [0.958]; normal values IL-6 &amp;lt;3.2 pg/mL) to follow up at all time points after initiating sutimlimab treatment (Figure 1), showing rapid onset and durable pattern of decline as early as Week 1 (2.70 [0.839]). Mean IL-6 level was reduced by more than half by Week 3 (1.56 [0.297]), slightly rose at Week 5 (1.88 [0.383]), and was lowest at TAT (1.31 [0.201]). Mean IL-10 level (pg/mL [SEM]) also decreased in a time-dependent manner from baseline (1.36 [0.310]) initially at Week 1 (0.99 [0.250]). Mean IL-10 slightly increased at Week 3 (1.07 [0.306]), but dropped at Week 5 (0.83 [0.142]) and was lowest by TAT (0.82 [0.129]) with sutimlimab treatment (Figure 2). At baseline, mean (SEM) FACIT-F score was 32.5 (2.266) (Figures 1-2). Patient FACIT-F scores showed early and late improvements with mean score increases at Week 1 (39.67 [1.741]), Week 3 (40.70 [1.543]), Week 5 (43.75 [1.192]), and at TAT (41.86 [1.958]). Decreased inflammation, as demonstrated by IL-6 and IL-10 activity, occurred concurrently with FACIT-F score improvements over time. Conclusions In Cardinal Part A, decrease from baseline to TAT in mean proinflammatory cytokine IL-6 and regulatory cytokine IL-10 levels were observed during sutimlimab treatment, highlighting the influence of complement inhibition on inflammation in CAD. Improved FACIT-F scores are concurrent with sutimlimab treatment and inhibition of the CP. Concurrent inverse changes were noted between select inflammatory cytokines and improvements in patients' fatigue, suggesting complement-mediated inflammation may additionally contribute to manifestation of fatigue in patients with CAD. Disclosures Weitz: Apellis: Consultancy, Honoraria; Alexion: Consultancy, Honoraria, Speakers Bureau. Ueda:Novartis: Honoraria; Alexion Pharmaceuticals: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria. Shafer:Sanofi: Current Employment. Su:Sanofi: Current Employment. Foster:Sanofi Genzyme: Current Employment. Storek:Sanofi: Current Employment. Patel:Sanofi: Current Employment.

Measuring the Motor Aspect of Cancer-Related Fatigue using a Handheld Dynamometer.

Cancer-related fatigue (CRF) is commonly reported by patients both during and after receiving treatment for cancer. Current CRF diagnoses rely on self-report questionnaires which are subject to report and recall biases. Objective measurements using a handheld dynamometer, or handgrip device, have been shown in recent studies to correlate significantly with subjective self-reported fatigue scores. However, variations of both the handgrip fatigue test and fatigue index calculations exist in the literature. The lack of standardized methods limits the utilization of the handgrip fatigue test in the clinical and research settings. In this study, we provide detailed methods for administering the physical fatigue test and calculating the fatigue index. These methods should supplement existing self-reported fatigue questionnaires and help clinicians assess fatigue symptom severity in an objective and quantitative manner.

Reader response: Depressed TSH level as a predictor of poststroke fatigue in patients with acute ischemic stroke.

Wang et al.1 reported that in patients with acute ischemic stroke, lower concentrations of thyroid-stimulating hormone were associated with greater fatigue symptom severity in acute phase and at follow-up. The article contributes to the growing body of literature underscoring the importance of thyroid axis function for clinical and patient-centered outcomes of cerebrovascular disorders.2

Cerebral blood flow and heart rate variability predict fatigue severity in patients with chronic fatigue syndrome.

Prolonged, disabling fatigue is the hallmark of chronic fatigue syndrome (CFS). Previous neuroimaging studies have provided evidence for nervous system involvement in CFS etiology, including perturbations in brain structure/function. In this arterial spin labeling (ASL) MRI study, we examined variability in cerebral blood flow (CBFV) and heart rate (HRV) in 28 women: 14 with CFS and 14 healthy controls. We hypothesized that CBFV would be reduced in individuals with CFS compared to healthy controls, and that increased CBFV and HRV would be associated with lower levels of fatigue in affected individuals. Our results provided support for these hypotheses. Although no group differences in CBFV or HRV were detected, greater CBFV and more HRV power were both associated with lower fatigue symptom severity in individuals with CFS. Exploratory statistical analyses suggested that protective effects of high CBFV were greatest in individuals with low HRV. We also found novel evidence of bidirectional association between the very high frequency (VHF) band of HRV and CBFV. Taken together, the results of this study suggest that CBFV and HRV are potentially important measures of adaptive capacity in chronic illnesses like CFS. Future studies should address these measures as potential therapeutic targets to improve outcomes and reduce symptom severity in individuals with CFS.

Open-Label Placebo Treatment for Cancer-Related Fatigue: A Randomized-Controlled Clinical Trial

The purpose of this 21-day assessor blinded, randomized-controlled trial was to compare an open-label placebo (OLP) to treatment as usual (TAU) for cancer survivors with fatigue. This was followed by an exploratory 21-day study in which TAU participants received OLPs while OLP participants in the main study were followed after discontinuing placebos. Cancer survivors (N = 74) who completed cancer treatment 6 months to 10 years prior to enrollment reporting at least moderate fatigue (i.e., ≥4 on a 0–10 scale) were randomized to OLP or TAU. Those randomized to OLP took 2 placebo pills twice a day for 21 days. Compared to those randomized to TAU, OLP participants reported a 29% improvement in fatigue severity (average difference in the mean change scores (MD) 12.47, 95% CI 3.32, 21.61; P = 0.008), medium effect (d = 0.63), and a 39% improvement in fatigue-disrupted quality of life (MD = 11.76, 95% CI 4.65, 18.86; P = 0.002), a large effect (d = 0.76). TAU participants who elected to try OLP for 21-days after the main study reported reductions in fatigue of a similar magnitude for fatigue severity and fatigue-disrupted quality of life (23% and 35%, respectively). OLP may reduce fatigue symptom severity and fatigue-related quality of life disruption in cancer survivors.

Association of thyroid hormone concentrations with quality of life of primary brain tumor patients: a pilot study.

Reduced triiodothyronine (T3) concentrations were implicated in worse prognosis of brain tumor patients. In this study we investigated the association of normal and abnormal thyroid hormone concentrations with health-related quality of life (HRQoL) of patients with primary brain tumors. Sixty-three patients (67% women and a mean age of 55.5 ± 13.8years) before brain tumor surgery were evaluated for: (1) HRQoL using the EORTC questionnaire for cancer patients (QLQ-C30) and the Brain Cancer-Specific Quality of Life Questionnaire (QLQ-BN20); (2) functional status (Barthel Index); and (3) clinical disease severity. Blood samples were obtained for assessment of thyroid hormone concentrations before surgery. After adjusting for the brain tumor histological diagnosis, patients' age, gender and functional status, lower thyroid stimulating hormone (TSH) concentrations were associated with poor levels of functioning on the QLQ-C30 scales: physical functioning (β = 0.395, p < 0.001), role functioning (β = 0.334, p = 0.003) and cognitive functioning (β = 0.327, p = 0.009), and with greater QLQ-BN20 fatigue symptom severity (β = -0.406, p < 0.001). Lower free T3 concentrations were associated with worse HRQOL on the QLQ-C30 global health status (β = 0.302, p = 0.017), emotional functioning (β= 0.422, p < 0.001) and cognitive functioning (β= 0.259, p = 0.042) domains, and with greater symptom severity on the QLQ-BN20 fatigue (β = -0.238, p = 0.041), motor dysfunction (β = -0.283, p = 0.013) and weakness of legs (β = -0.269. p = 0.027) domains. In conclusion, reduced T3 and TSH hormone concentrations are associated with impaired emotional and physical aspects of HRQoL of primary brain tumor patients independent of brain tumor histological diagnosis, patients' age, gender and functional status. Assessment for thyroid axis dysfunction should be addressed and appropriately managed in neuro-oncology patient care.

Brain Correlates of Human Leukocyte Antigen (HLA) Protection in Gulf War Illness (GWI)

BackgroundWe recently reported that six alleles from class II genes of the Human Leukocyte Antigen (HLA) confer protection from Gulf War Illness (GWI) (Georgopoulos et al., 2015). The most significant effect is exerted on Neurological-Cognitive-Mood (NCM), Pain, and Fatigue symptoms, such that higher number of copies of the protective alleles are associated with lower symptom severity. Here we tested the hypothesis that this effect is exerted by modulating the strength of neural synchronicity. MethodsEighty-one Gulf War veterans (65 with GWI and 16 healthy controls) underwent a magnetoencephalography (MEG) scan to assess the strength of brain synchronicity by computing zero-lag crosscorrelations (and their Fisher z transforms) between prewhitened MEG time series. A high-resolution HLA genotyping determined the number of copies, k, of the 6 protective alleles above in each participant. We tested the hypothesis above by regressing NCM, Pain and Fatigue symptom severity against the interaction term, k×z (HLA-related effect), while including z (non-HLA-related effect), gender and age as covariates. The k×z and z terms assessed HLA- and non-HLA-related effects, respectively, of neural synchronicity on symptom severity. The distributions of these effects in sensor space were visualized using statistical heatmaps. FindingsWe found significant, graded HLA- and non-HLA-related effects: (a) NCM>Pain>Fatigue for HLA-related effects, (b) NCM>Fatigue>Pain for non-HLA-related effects, and (c) HLA-related>non-HLA-related effects for all symptoms. These effects had widespread but distinct distributions in sensor space that allowed the orderly separation of the 6 terms (3 symptom domains×2 HLA factors) in a multidimensional plot, where one dimension separated the symptoms and the other the HLA relation. InterpretationThese findings demonstrate the presence of substantial, widespread, distinct and orderly HLA- and non-HLA-related neural influences on NCM, Pain and Fatigue symptom severity in GWI. FundingU.S. Department of Veterans Affairs and University of Minnesota.

Reduced cardiac volumes in chronic fatigue syndrome associate with plasma volume but not length of disease: a cohort study

ObjectivesTo explore potential mechanisms that underpin the cardiac abnormalities seen in chronic fatigue syndrome (CFS) using non-invasive cardiac impedance, red cell mass and plasma volume measurements.MethodsCardiac MR (MR) examinations were...

PedsQL™ multidimensional fatigue scale in sickle cell disease: Feasibility, reliability, and validity

Sickle cell disease (SCD) is an inherited blood disorder characterized by a chronic hemolytic anemia that can contribute to fatigue and global cognitive impairment in patients. The study objective was to report on the feasibility, reliability, and validity of the PedsQL™ Multidimensional Fatigue Scale in SCD for pediatric patient self-report ages 5-18 years and parent proxy-report for ages 2-18 years. This was a cross-sectional multi-site study whereby 240 pediatric patients with SCD and 303 parents completed the 18-item PedsQL™ Multidimensional Fatigue Scale. Participants also completed the PedsQL™ 4.0 Generic Core Scales. The PedsQL™ Multidimensional Fatigue Scale evidenced excellent feasibility, excellent reliability for the Total Scale Scores (patient self-report α = 0.90; parent proxy-report α = 0.95), and acceptable reliability for the three individual scales (patient self-report α = 0.77-0.84; parent proxy-report α = 0.90-0.97). Intercorrelations of the PedsQL™ Multidimensional Fatigue Scale with the PedsQL™ Generic Core Scales were predominantly in the large (≥0.50) range, supporting construct validity. PedsQL™ Multidimensional Fatigue Scale Scores were significantly worse with large effects sizes (≥0.80) for patients with SCD than for a comparison sample of healthy children, supporting known-groups discriminant validity. Confirmatory factor analysis demonstrated an acceptable to excellent model fit in SCD. The PedsQL™ Multidimensional Fatigue Scale demonstrated acceptable to excellent measurement properties in SCD. The results demonstrate the relative severity of fatigue symptoms in pediatric patients with SCD, indicating the potential clinical utility of multidimensional assessment of fatigue in patients with SCD in clinical research and practice.

Trajectory of fatigue severity in natalizumab treated multiple sclerosis patients

Fatigue is one of the most debilitating symptoms in multiple sclerosis (MS). The aim of this study was to observe the severity of MS associated fatigue in a community-based sample of natalizumab (ntz) treated patients over one year. In 48 relapsing remitting MS patients (mean age=38.3 years) fatigue was longitudinally measured with the Modified Fatigue Impact Scale (MFIS) at two time points. The primary analysis of differences in MFIS was performed using non-parametric Wilcoxon test for dependent variables. Mean total MFIS Score increased significantly from 32.6±20.9 to 49.1±20.0 over the observation period of 12 months (p<0.001). 83% of patients remained clinically disease activity free (no relapse, no progression in the Expanded Disability Status Scale, EDSS) over the observation period of one year. Age, gender, disease duration, spinal involvement, Gd-enhancement, depressive symptoms and EDSS had no influence on fatigue levels as measured with MFIS. Severity of fatigue symptoms during ntz treatment might increase despite very low disease activity.

Assessment of Fatigue in Pediatric Patients With Short Stature Utilizing the PedsQL™ Multidimensional Fatigue Scale

The standardized multidimensional assessment of fatigue has not been previously conducted in pediatric patients with short stature. Consequently, the objective of this exploratory study was to assess fatigue in a heterogeneous sample of pediatric patients with short stature utilizing the Pediatric Quality of Life Inventory™ (PedsQL™) Multidimensional Fatigue Scale. The 18-item PedsQL Multidimensional Fatigue Scale (general fatigue, sleep/rest fatigue, and cognitive fatigue domains) and the 23-item PedsQL 4.0 Generic Core Scales (physical, emotional, social, and school functioning) were completed by 29 pediatric patients with a physician diagnosis of short stature and 31 parents from a hospital-based pediatric endocrinology clinic. Pediatric patients with short stature experienced more fatigue and impaired generic health-related quality of life (HRQOL) than healthy children, demonstrating comparable fatigue to pediatric patients receiving cancer treatment. Cognitive fatigue and school functioning were reported by both pediatric patients and their parents as most impaired. The results demonstrate the relative severity of fatigue symptoms and impaired HRQOL in pediatric patients with short stature, indicating the potential clinical utility of the standardized multidimensional assessment of fatigue and HRQOL in these patients on a routine basis.