Psychometric properties of the Spanish version of the Chalder Fatigue Scale in clinical and general populations / Propiedades psicométricas de la versión española de la Escala de Fatiga de Chalder en población clínica y general

Objetivo: La Escala de Fatiga de Chalder (CFS) es una escala breve para evaluar fatiga que se utiliza en España, pero que no ha sido validada en su población. El objetivo del estudio fue adaptar y evaluar las propiedades psicométricas de la versión española de la CFS (Sp-CFS). Método: La muestra la conformaron 3,671 participantes (3.190 de la población general y 481 pacientes), con edades entre 18 y 86 años (M = 28.43; DT = 12.71), siendo el 67.6% mujeres. Las propiedades psicométricas de la escala se probaron en un diseño transversal utilizando validación cruzada (análisis factorial exploratorio y confirmatorio) y estimación de la invarianza (sexo y condición clínica). Resultados: Un modelo de cuatro factores (baja energía, problemas de sueño, problemas de concentración y disfunción cognitiva subjetiva) en lugar de un modelo original de dos factores (fatiga física y mental) proporcionó mejores índices de bondad de ajuste a los datos. La consistencia interna y la estabilidad de la escala fueron excelentes. Su validez convergente se apoyó en su asociación significativa con la ansiedad, la depresión, el estrés y los síntomas positivos y negativos del espectro de la psicosis. El instrumento no mostró diferencias significativas entre sexos ni condiciones clínicas, y discriminó entre la población general y los pacientes, obteniendo estos últimos puntajes significativamente mayores. Conclusiones: Sp-CFS es una escala fiable y válida para medir la fatiga en población general y clínica española.(AU)

Objective:The Chalder Fatigue Scale (CFS) is a brief self-report screening scale for fatigue that is used in Spain but has not been validated for the Spanish population. The aim of this study was to adapt and evalu-ate the psychometric properties of the Spanish version of the CFS (Sp-CFS). Method:The sample consisted of 3,671 participants (3,190 from the general population and 481 patients), aged 18 to 86 years (M=28.43; DT=12.71), 67.6% of whom were women. Psychometric properties of the scale were tested in a cross-sectional design using cross-validation (explora-tory and confirmatory factor analysis) and estimation of invariance (sex and clinical condition). Results:A four-factor model (low energy, sleep problems, concentration problems and subjective cognitive dysfunction) rather than an original two-factor model (physical and mental fatigue) pro-vided better indices of goodness of fit to the data. The internal consistencyand stability of the scale were excellent. Its convergent validity was sup-ported by its significant association with anxiety, depression, stress, and the positive and negative symptoms of the psychosis spectrum. The instru-ment did not show significant differences between sexes or clinical condi-tions, and it discriminated between the general population and the patients, with the latter obtaining significantly greater scores. Conclusions: Sp-CFS is a reliable and valid scale for measuring a transdiagnostic construct such as fatigue in Spanish general and clinical populations.(AU)

The Effect of Aromatherapy with Lavender Essential Oil on the Sleep and Fatigue Level of Patients with Multiple Sclerosis in Turkey: A Randomized Controlled Trial.

BACKGROUND: Fatigue is a common problem in patients with multiple sclerosis (MS) and is one of the most serious symptoms of the disease. Although many factors play a role in the etiology of fatigue in patients with MS, it has been reported that fatigue is caused by irregular or disrupted sleep patterns. AIM: The purpose of the study was to examine the effects of lavender oil aromatherapy on the sleep and fatigue of MS patients. METHODS: The study was designed as a randomized controlled trial and was conducted in Turkey. The data of the study were collected using the Patient Description Form, Fatigue Severity Scale, and Pittsburgh Sleep Quality Index. RESULTS: The mean FSS score in the experimental group was 6.86 ± 0.94 before the procedure and 3.42 ± 0.85 after the procedure, the mean PSQI score was 9.45 ± 1.23 before the procedure and 6.68 ± 2.87 after the procedure, and the difference in the mean scores between the two groups was found to be statistically significant (P < 0.001). CONCLUSION: The results showed that aromatherapy with lavender essential oil has significant impacts on fatigue and sleep in MS patients. Lavender essential oil aromatherapy can be used by nurses as an independent nursing practice. It is an inexpensive, noninvasive, and reliable technique to manage fatigue in individuals with MS.

Systematic review of fatigue severity in ME/CFS patients: insights from randomized controlled trials.

BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating illness medically unexplained, affecting approximately 1% of the global population. Due to the subjective complaint, assessing the exact severity of fatigue is a clinical challenge, thus, this study aimed to produce comprehensive features of fatigue severity in ME/CFS patients. METHODS: We systematically extracted the data for fatigue levels of participants in randomized controlled trials (RCTs) targeting ME/CFS from PubMed, Cochrane Library, Web of Science, and CINAHL throughout January 31, 2024. We normalized each different measurement to a maximum 100-point scale and performed a meta-analysis to assess fatigue severity by subgroups of age, fatigue domain, intervention, case definition, and assessment tool, respectively. RESULTS: Among the total of 497 relevant studies, 60 RCTs finally met our eligibility criteria, which included a total of 7088 ME/CFS patients (males 1815, females 4532, and no information 741). The fatigue severity of the whole 7,088 patients was 77.9 (95% CI 74.7-81.0), showing 77.7 (95% CI 74.3-81.0) from 54 RCTs in 6,706 adults and 79.6 (95% CI 69.8-89.3) from 6 RCTs in 382 adolescents. Regarding the domain of fatigue, 'cognitive' (74.2, 95% CI 65.4-83.0) and 'physical' fatigue (74.3, 95% CI 68.3-80.3) were a little higher than 'mental' fatigue (70.1, 95% CI 64.4-75.8). The ME/CFS participants for non-pharmacological intervention (79.1, 95% CI 75.2-83.0) showed a higher fatigue level than those for pharmacological intervention (75.5, 95% CI 70.0-81.0). The fatigue levels of ME/CFS patients varied according to diagnostic criteria and assessment tools adapted in RCTs, likely from 54.2 by ICC (International Consensus Criteria) to 83.6 by Canadian criteria and 54.2 by MFS (Mental Fatigue Scale) to 88.6 by CIS (Checklist Individual Strength), respectively. CONCLUSIONS: This systematic review firstly produced comprehensive features of fatigue severity in patients with ME/CFS. Our data will provide insights for clinicians in diagnosis, therapeutic assessment, and patient management, as well as for researchers in fatigue-related investigations.

Longitudinal multisite study of the chronobiological control of chronic pain: the CircaHealth CircaPain study protocol.

INTRODUCTION: One in five Canadians lives with chronic pain. Evidence shows that some individuals experience pain that fluctuates in intensity following a circadian (24-hour) rhythm. Endogenous molecular rhythms regulate the function of physiological processes that govern pain mechanisms. Addressing chronic pain rhythmicity on a molecular and biopsychosocial level can advance understanding of the disease and identify new treatment/management strategies. Our CircaHealth CircaPain study uses an online survey combined with ecological momentary assessments and biosample collection to investigate the circadian control of chronic pain and identify potential biomarkers. Our primary objective is to understand interindividual variability in pain rhythmicity, by collecting biopsychosocial measures. The secondary objective accounts for seasonal variability and the effect of latitude on rhythmicity. METHODS AND ANALYSIS: Following completion of a baseline questionnaire, participants complete a series of electronic symptom-tracking diaries to rate their pain intensity, negative affect, fatigue and stress on a 0-10 scale at 8:00, 14:00 and 20:00 daily over 10 days. These measures are repeated at 6 and 12 months postenrolment to account for potential seasonal changes. We aim to recruit ≥2500 adults with chronic pain within Canada. Infrastructure is being developed to facilitate the collection of blood samples from subgroups of participants (~800) two times per day over 24-48 hours to identify rhythmic expression of circulating genes and/or proteins. ETHICS AND DISSEMINATION: Ethical approval for this study was obtained by the Queen's University Health Sciences and Affiliated Teaching Hospitals Research Ethics Board (File No. 6038114). Participants provide informed consent to participate, and their data will not be identifiable in any publication or report. Findings will be published in a relevant scientific journal and disseminated at scientific meetings and online webinars. We maintain a website to post updated resources and engage with the community. We employ knowledge mobilisation in the form of direct data sharing with participants.

Disrupted hemodynamic response within dorsolateral prefrontal cortex during cognitive tasks among people with multiple sclerosis-related fatigue.

INTRODUCTION: Mental fatigue is an early and enduring symptom in persons with autoimmune disease particularly multiple sclerosis (MS). Neuromodulation has emerged as a potential treatment although optimal cortical targets have yet to be determined. We aimed to examine cortical hemodynamic responses within bilateral dorsolateral prefrontal cortex (dlPFC) and frontopolar areas during single and dual cognitive tasks in persons with MS-related fatigue compared to matched controls. METHODS: We recruited persons (15 MS and 12 age- and sex-matched controls) who did not have physical or cognitive impairment and were free from depressive symptoms. Functional near infrared spectroscopy (fNIRS) registered hemodynamic responses during the tasks. We calculated oxyhemoglobin peak, time-to-peak, coherence between channels (a potential marker of neurovascular coupling) and functional connectivity (z-score). RESULTS: In MS, dlPFC demonstrated disrupted hemodynamic coherence during both single and dual tasks, as evidenced by non-significant and negative correlations between fNIRS channels. In MS, reduced coherence occurred in left dorsolateral PFC during the single task but occurred bilaterally as the task became more challenging. Functional connectivity was lower during dual compared to single tasks in the right dorsolateral PFC in both groups. Lower z-score was related to greater feelings of fatigue. Peak and time-to-peak hemodynamic response did not differ between groups or tasks. CONCLUSIONS: Hemodynamic responses were inconsistent and disrupted in people with MS experiencing mental fatigue, which worsened as the task became more challenging. Our findings point to dlPFC, but not frontopolar areas, as a potential target for neuromodulation to treat cognitive fatigue.

Combined Aerobic and Resistance Training Improves Body Composition, Alters Cardiometabolic Risk, and Ameliorates Cancer-Related Indicators in Breast Cancer Patients and Survivors with Overweight/Obesity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Breast cancer survivors with obesity are at a high risk of cancer recurrence, comorbidity, and mortality. This review aims to systematically evaluate the effects of combined aerobic and resistance training (CART) on body composition, lipid homeostasis, inflammation, adipokines, cancer-related fatigue, sleep, and quality of life in breast cancer patients and survivors with overweight/obesity. An electronic search was conducted in PubMed, Web of Science, Scopus, Science Direct, Cochrane, and Google Scholar databases from inception up to January 8, 2024. Randomized controlled trials (RCTs) meeting the inclusion criteria were selected for the analysis. The Cochrane risk of bias tool was used to assess eligible studies, and the GRADE method to evaluate the quality of evidence. A random-effects model was used, and data were analyzed using mean (MD) and standardized mean differences (SMD) for continuous variables with 95% confidence intervals (CI). We assessed the data for risk of bias, heterogeneity, sensitivity, reporting bias, and quality of evidence. A total of 17 randomized controlled trials were included in the systematic review involving 1,148 female patients and survivors (mean age: 54.0 ± 3.4 years). The primary outcomes showed significant improvements in body mass index (SMD -0.57 kg/m2, p = 0.04), body fat (SMD -0.50%, p = 0.02), fat mass (SMD -0.63 kg, p = 0.04), hip circumference (MD -3.14 cm, p = 0.02), and fat-free mass (SMD 1.03 kg, p < 0.001). The secondary outcomes indicated significant increases in high-density lipoprotein cholesterol (MD -0.05 mmol/L, p = 0.008), natural killer cells (SMD 0.42%, p = 0.04), reductions in triglycerides (MD -81.90 mg/dL, p < 0.01), total cholesterol (SMD -0.95 mmol/L, p < 0.01), tumor necrosis factor α (SMD -0.89 pg/mL, p = 0.03), and leptin (SMD -0.63 ng/mL, p = 0.03). Also, beneficial alterations were found in cancer-related fatigue (SMD -0.98, p = 0.03), sleep (SMD -1.17, p < 0.001), and quality of life (SMD 2.94, p = 0.02) scores. There was very low to low confidence in the estimated effect of most of the outcomes. The present findings reveal that CART could be considered an adjunct therapy in supporting the conventional clinical approach observed following exercise. However, further high-quality research is needed to evaluate whether CART would be a valuable intervention to lower aggressive pharmacologic use in breast cancer patients with overweight/obesity.

Prevalence of somatic symptoms among Ebola Virus Disease (EVD) survivors in Africa: a systematic review and meta-analysis.

BACKGROUND: Many Ebola virus disease (EVD) survivors have reported somatic and neuropsychological symptoms after discharge from the Ebola Treatment Unit (ETU). Since the 2014-2016 Ebola epidemic in West Africa, various studies have investigated and identified these symptoms. Evidence on somatic symptoms is widely available in the literature, however, there is no concise overview of the prevalence across different time intervals. METHODS: This meta-analysis was conducted following the (PRISMA) guidelines. A database search was conducted to identify original studies that reported the prevalence of symptoms. The primary outcome measure was the prevalence rate of several somatic symptoms. Results were pooled, and prevalence rates were assessed over time, to elucidate any particular trends. RESULTS: We included 23 studies (5,714 participants). The pooled prevalence was: arthralgia 50% (95% CI: 41%-59%); headache 44% (95% CI: 36%-52%); myalgia 32% (95% CI: 26%-38%); abdominal pain 27% (95% CI: 15%-39%); fatigue 25% (95% CI: 19%-31%); numbness of feet 16% (95% CI: 14%-18%); numbness of hands 12% (95% CI: 10%-14%) and hearing loss 9% (95% CI: 5%-12%). Prevalence across different time intervals revealed significant patterns. All the symptoms persisted for more than 2 years after discharge except for abdominal pain. CONCLUSION: The pooled prevalence rates of somatic symptoms are notably high. Arthralgia and headache are the most prevalent of the symptoms, with hearing loss and numbness in hands and feet being the least. We found that arthralgia, myalgia, and abdominal pain decreased over time. However, headache, fatigue, numbness of hands and feet, and hearing loss increased over time.

Connecting the dots: the role of fatigue in female infertility.

Fatigue, an increasingly acknowledged symptom in various chronic diseases, has garnered heightened attention, during the medical era of bio-psycho-social model. Its persistence not only significantly compromises an individual's quality of life but also correlates with chronic organ damage. Surprisingly, the intricate relationship between fatigue and female reproductive health, specifically infertility, remains largely unexplored. Our exploration into the existing body of evidence establishes a compelling link between fatigue with uterine and ovarian diseases, as well as conditions associated with infertility, such as rheumatism. This observation suggests a potentially pivotal role of fatigue in influencing overall female fertility. Furthermore, we propose a hypothetical mechanism elucidating the impact of fatigue on infertility from multiple perspectives, postulating that neuroendocrine, neurotransmitter, inflammatory immune, and mitochondrial dysfunction resulting from fatigue and its co-factors may further contribute to endocrine disorders, menstrual irregularities, and sexual dysfunction, ultimately leading to infertility. In addition to providing this comprehensive theoretical framework, we summarize anti-fatigue strategies and accentuate current knowledge gaps. By doing so, our aim is to offer novel insights, stimulate further research, and advance our understanding of the crucial interplay between fatigue and female reproductive health.

Effects of Mindfulness-Based Cancer Recovery training on anxiety, depression, post-traumatic stress disorder, and cancer-related fatigue in breast neoplasm patients undergoing chemotherapy.

RATIONALE: Mindfulness-Based Cancer Recovery (MBCR) program is a group course training for cancer patients that combines cancer knowledge and psychological knowledge, emphasizing focusing on the psychosomatic symptoms of cancer patients. Currently, the application value of Mindfulness-Based Cancer Recovery in improving psychosomatic health of cancer patients has been confirmed, however, its intervention effect on breast neoplasm patients has not yet been widely studied in China. PATIENT CONCERNS AND DIAGNOSES: This study introduced the Mindfulness-Based Cancer Recovery protocol into the rehabilitation process of breast cancer patients, aiming to elucidate the effects of Mindfulness-Based Cancer Recovery on anxiety, depression, post-traumatic stress disorder, and cancer-related fatigue in breast neoplasm patients, to provide a practical basis for improving the physical and mental health of breast cancer patients. INTERVENTION: In this study, 80 patients with chemotherapy-stage breast neoplasm attending the oncology department of a tertiary-level hospital from January 2022 to December 2022 were selected, 40 patients attending from January 2022 to June 2022 were included in the study group, and 40 patients attending from July 2022 to December 2022 were included in the control group. The control group was administered conventional care, and the study group was administered Mindfulness-Based Cancer Recovery based on conventional care in the control group for 8 weeks. After the intervention, hospital anxiety and depression scale, impact of event scale-revised, and cancer fatigue scale were used for evaluation. OUTCOMES: After the intervention, hospital anxiety and depression scale scores decreased in both groups compared with pre-intervention, with the study group scoring lower than the control group (P < .05). After the intervention, the impact of event scale-revised scores of the 2 groups decreased from the preintervention period, with the study group scoring lower than the control group (P < .05). After the intervention, cancer fatigue scale scores decreased in the 2 groups compared with the preintervention period, with the study group scoring lower than the control group (P < .05). LESSONS: Mindfulness-Based Cancer Recovery can effectively reduce the levels of anxiety, depression and post-traumatic stress disorder in breast neoplasm patients undergoing chemotherapy, reduce the levels of cancer-related fatigue, and promote the physical and mental health of patients.

Effectiveness of exercise rehabilitation on aplastic anemia patients receiving hematopoietic stem cell transplantation: study protocol for a randomized controlled trial.

BACKGROUND: Although hematopoietic stem cell transplantation provides the chances of survival for aplastic anemia patients, it is also related to many treatment-related physical and psychological side effects that severely influence the quality of life. Exercise interventions have shown positive results in mixed hematology populations. The study aims to determine the effectiveness of exercise rehabilitation in improving the quality of life, fatigue, and physical function in these patients. METHODS: The study will enroll a total of 82 aplastic anemia patients receiving hematopoietic stem cell transplantation. They will be randomly divided into two groups in a 1:1 ratio. The intervention group will participate in structured exercise rehabilitation (plus usual care), while control group participants will receive usual care. The exercise rehabilitation program will be performed from neutrophil and platelet engraftment until 100 days after transplantation. All outcomes will be measured at the following time points: the neutrophil and platelet engraftment (± 1day, T0), discharge from the transplantation module (± 1 day, T1), hospital discharge (± 1 day, T2), and 100 days post-transplantation (± 5 days, T3). DISCUSSION: This study aims to assess the effectiveness of exercise rehabilitation for aplastic anemia patients receiving hematopoietic stem cell transplantation in a Chinese single center. It is particularly vital to conduct the studies in this population. Moreover, the evidence obtained from the study will provide evidence for future research and clinical practice to exercise in aplastic anemia patients. TRIAL REGISTRATION: ChiCTR2200060762. Registered on May 2022, www.trialregister.nl/trial/7702.

Evaluation of walking activity and gait to identify physical and mental fatigue in neurodegenerative and immune disorders: preliminary insights from the IDEA-FAST feasibility study.

BACKGROUND: Many individuals with neurodegenerative (NDD) and immune-mediated inflammatory disorders (IMID) experience debilitating fatigue. Currently, assessments of fatigue rely on patient reported outcomes (PROs), which are subjective and prone to recall biases. Wearable devices, however, provide objective and reliable estimates of gait, an essential component of health, and may present objective evidence of fatigue. This study explored the relationships between gait characteristics derived from an inertial measurement unit (IMU) and patient-reported fatigue in the IDEA-FAST feasibility study. METHODS: Participants with IMIDs and NDDs (Parkinson's disease (PD), Huntington's disease (HD), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), primary Sjogren's syndrome (PSS), and inflammatory bowel disease (IBD)) wore a lower-back IMU continuously for up to 10 days at home. Concurrently, participants completed PROs (physical fatigue (PF) and mental fatigue (MF)) up to four times a day. Macro (volume, variability, pattern, and acceleration vector magnitude) and micro (pace, rhythm, variability, asymmetry, and postural control) gait characteristics were extracted from the accelerometer data. The associations of these measures with the PROs were evaluated using a generalised linear mixed-effects model (GLMM) and binary classification with machine learning. RESULTS: Data were recorded from 72 participants: PD = 13, HD = 9, RA = 12, SLE = 9, PSS = 14, IBD = 15. For the GLMM, the variability of the non-walking bouts length (in seconds) with PF returned the highest conditional R2, 0.165, and with MF the highest marginal R2, 0.0018. For the machine learning classifiers, the highest accuracy of the current analysis was returned by the micro gait characteristics with an intrasubject cross validation method and MF as 56.90% (precision = 43.9%, recall = 51.4%). Overall, the acceleration vector magnitude, bout length variation, postural control, and gait rhythm were the most interesting characteristics for future analysis. CONCLUSIONS: Counterintuitively, the outcomes indicate that there is a weak relationship between typical gait measures and abnormal fatigue. However, factors such as the COVID-19 pandemic may have impacted gait behaviours. Therefore, further investigations with a larger cohort are required to fully understand the relationship between gait and abnormal fatigue.

Association between nutritional risk and fatigue in frailty conditions for older adult patients: a multicentre cross-sectional survey study.

BACKGROUND AND AIMS: Frailty is widespread in the elderly, while there is a bi-directional relationship between frailty and malnutrition. The objectives of this study were to investigate the prevalence and correlation of frailty and nutritional risk in older adult patients and to analyse the factors associated with fatigue which is one indicator of frailty. METHODS: This cross-sectional multicentre survey study was conducted in five hospitals in the same city from 01 January 2021 to 01 December 2021. We collected information on gender, age, diseases, medication and dietary status. Frailty status was diagnosed using the FRAIL scale, and Nutritional Risk Screening-2002 was used to screen the nutritional risk. Spearman rank correlation was used to analyse the correlation between frailty and nutritional risk. Univariate and multivariate logistic regression analyses were used to analyse the risk factors related to fatigue in all patients and inpatients. RESULTS: Among 2016 older adult patients, the prevalence of frailty was 15.1% (305/2016), the prevalence of nutritional risk was 16.2% (327/2016) and the overlap prevalence of frailty and nutritional risk was 7.3% (147/2016). Multivariate analysis showed that nutritional risk (OR 3.109, 95% CI 2.384 to 4.056, p<0.001) was an independent risk factor for fatigue in all patients; similar results were found for nutritional risk (OR 2.717, 95% CI 2.068 to 3.571, p<0.001) in hospitalised patients. CONCLUSIONS: Frailty and nutritional risk are prevalent among older adult patients, and nutritional risk is associated with the occurrence of fatigue in older adult patients and older adult inpatients. TRIAL REGISTRATION NUMBER: China Clinical Trial Registry (Registered No. ChiCTR-EPC-14005253).

Afraid and tired: A longitudinal study of the relationship between cancer-related fatigue and fear of cancer recurrence in long-term cancer survivors.

OBJECTIVE: Cancer-related fatigue (CRF) and fear of cancer recurrence (FCR) are two common concerns experienced by cancer survivors. However, the relationship between these two concerns is poorly understood, and whether CRF and FCR influence each other over time is unclear. METHODS: Data were from a national, prospective, longitudinal study, the American Cancer Society's Study of Cancer Survivors-I (SCS-I). Surveys were completed by 1395 survivors of 10 different cancer types at three time-points, including assessment 1.3 years (T1), 2.2 years (T2) and 8.8 years (T3) following their cancer diagnosis. CRF was assessed using the fatigue-inertia subscale of the Profile of Mood States, and FCR by the FCR subscale of the Cancer Problems in Living Scale. Multiple group random intercepts cross-lagged panel models investigated prospective associations between CRF and FCR. RESULTS: For younger participants (at or below median age of 55 years, n = 697), CRF at T1 and T2 marginally and significantly predicted FCR at T2 and T3, respectively, but no lagged effects of FCR on subsequent CRF were observed. Cross-lagged effects were not observed for survivors over 55 years of age. CONCLUSION: Both CRF and FCR are debilitating side effects of cancer and its treatments. Given that CRF may be predictive of FCR, it possible that early detection and intervention for CRF could contribute to lowering FCR severity.

SF-36v2 and FACIT-Fatigue quality of life improvements with organ-specific SELENA-SLEDAI response and belimumab treatment in patients with systemic lupus erythematosus.

OBJECTIVE: Explore organ-specific SLE burden by assessing health-related quality of life (HRQoL) and fatigue changes associated with Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) organ system response (score improvement) and belimumab treatment. METHODS: Data from four phase III belimumab trials were pooled for post hoc analysis (GSK Study 217382): BLISS-52 (NCT00424476), BLISS-76 (NCT00410384), BLISS-SC (NCT01484496) and EMBRACE (NCT01632241). Patients with baseline organ system involvement were classed as organ system responders if SELENA-SLEDAI scores for that organ system decreased at any post-baseline visit. HRQoL (36-Item Short Form Health Survey version 2 (SF-36v2)) and fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue)) changes over 52 weeks were compared between organ system responders and non-responders, and separately between belimumab versus placebo treatment arms among organ system responders. Group-level differences were compared using analysis of variance; differences were interpreted using published group-level minimal important difference (MID). RESULTS: In these post hoc analyses, musculoskeletal and mucocutaneous organ system responders had greater SF-36v2 improvements than non-responders across most SF-36v2 domains, but differences were largely MID), with FACIT-Fatigue also improving >MID for renal responders receiving belimumab. CONCLUSIONS: SLE disease burden differs with the organ system(s) involved. While these analyses are limited by mutual inclusivity of organ system groupings, differing patient numbers between groups and small numbers in some groups, they suggest that mucocutaneous and musculoskeletal organ system response improves SF-36v2 domain scores; cardiovascular and respiratory organ system response may meaningfully improve fatigue; and belimumab may offer additional HRQoL or fatigue benefits beyond standard therapy for musculoskeletal and renal responders.

Anti-fatigue activity of methyl dihydrojasmonate and linalool in a rat model evaluated by a novel index for neuro-immune and oxidative stress interactions.

Avoiding fatigue is a long-standing challenge in both healthy and diseased individuals. Establishing objective standard markers of fatigue is essential to evaluate conditions in spatiotemporally different locations and individuals and identify agents to fight against fatigue. Herein, we introduced a novel method for evaluating fatigue using nervous system markers (including dopamine, adrenaline, and noradrenaline), various cytokine levels (such as interleukin [IL]-1ß, tumor necrosis factor [TNF]-α, IL-10, IL-2, IL-5 and IL-17A), and oxidative stress markers (such as diacron-reactive oxygen metabolites [d-ROMs] and biological antioxidant potential [BAP]) in a rat fatigue model. Using this method, the anti-fatigue effects of methyl dihydrojasmonate (MDJ) and linalool, the fragrance/flavor compounds used in various products, were assessed. Our method evaluated the anti-fatigue effects of the aforementioned compounds based on the changes in levels of the nerves system markers, cytokines, and oxidative stress markers. MDJ exerted more potent anti-fatigue effects than linalool. In conclusion, the reported method could serve as a useful tool for fatigue studies and these compounds may act as effective therapeutic agents for abrogating fatigue symptoms.

Experimental study on the antifatigue effect of icariin.

Fatigue is a serious disturbance to human health, especially in people who have a severe disease such as cancer, or have been infected with COVID-19. Our research objective is to evaluate the anti-fatigue effect and mechanism of icariin through a mouse experimental model. Mice were treated with icariin for 30 days and anti-fatigue effects were evaluated by the weight-bearing swimming test, serum urea nitrogen test, lactic acid accumulation and clearance test in blood and the amount of liver glycogen. The protein expression levels of adenosine monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC1-α) in the skeletal muscle of mice in each group were measured by western blotting. Results showed that icariin prolonged the weight-bearing swimming time of animals, reduced the serum urea nitrogen level after exercise, decreased the blood lactic acid concentration after exercise and increased the liver glycogen content observably. Compared to that in the control group, icariin upregulated AMPK and PGC1-α expression in skeletal muscle. Icariin can improve fatigue resistance in mice and its mechanism may be through improving the AMPK/PGC-1α pathway in skeletal muscle to enhance energy synthesis, decreasing the accumulation of metabolites and slowing glycogen consumption and decomposition.

A phase II randomized, double-blind, placebo-controlled study of Nuvastatic (C50SEW505OESA), a standardized rosmarinic acid-rich polymolecular botanical extract formulation to reduce cancer-related fatigue in patients with solid tumors.

AIM: We evaluated the efficacy and safety of Nuvastatic™ (C5OSEW5050ESA) in improving cancer-related fatigue (CRF) among cancer patients. METHODS: This multicenter randomized double-blind placebo-controlled phase 2 trial included 110 solid malignant tumor patients (stage II-IV) undergoing chemotherapy. They were randomly selected and provided oral Nuvastatic™ 1000 mg (N = 56) or placebo (N = 54) thrice daily for 9 weeks. The primary outcomes were fatigue (Brief Fatigue Inventory (BFI)) and Visual Analog Scale for Fatigue (VAS-F)) scores measured before and after intervention at baseline and weeks 3, 6, and 9. The secondary outcomes were mean group difference in the vitality subscale of the Medical Outcome Scale Short Form-36 (SF-36) and urinary F2-isoprostane concentration (an oxidative stress biomarker), Eastern Cooperative Oncology Group scores, adverse events, and biochemical and hematologic parameters. Analysis was performed by intention-to-treat (ITT). Primary and secondary outcomes were assessed by two-way repeated-measures analysis of variance (mixed ANOVA). RESULTS: The Nuvastatic™ group exhibited an overall decreased fatigue score compared with the placebo group. Compared with the placebo group, the Nuvastatic™ group significantly reduced BFI-fatigue (BFI fatigue score, F (1.4, 147) = 16.554, p < 0.001, partial η2 = 0.333). The Nuvastatic™ group significantly reduced VAS-F fatigue (F (2, 210) = 9.534, p < 0.001, partial η2 = 0.083), improved quality of life (QoL) (F (1.2, 127.48) = 34.07, p < 0.001, partial η2 = 0.243), and lowered urinary F2-IsoP concentrations (mean difference (95% CI) = 55.57 (24.84, 86.30)), t (55) = 3.624, p < 0.001, Cohen's d (95% CI) = 0.48 (0.20, 0.75)). Reported adverse events were vomiting (0.9%), fever (5.4%), and headache (2.7%). CONCLUSION: Nuvastatic™ is potentially an effective adjuvant for CRF management in solid tumor patients and worthy of further investigation in larger trials. TRIAL REGISTRATION: ClinicalTrial.gov ID: NCT04546607. Study registration date (first submitted): 11-05-2020.

Symptom cluster among cancer survivors from a nationally representative survey: a network analysis.

PURPOSE: To identify the symptom cluster among cancer survivors and examine their subgroup differences via network analysis based on nationally representative data. METHODS: This cross-sectional study included 2966 survivors participating in the 2020 National Health Interview Survey (NHIS). Participants self-reported the presence of 14 symptoms capturing four clusters (physical, somatic, sleep, and psychologic problems). Network analysis models were used to reveal the relationships between symptoms and those interactions. Network comparison tests were applied to compare subgroups. RESULTS: The core symptoms of the symptom cluster were fatigue (Bet = 33, Clo = 0.0067, Str = 0.9397), pain (Bet = 11, Clo = 0.0060, Str = 0.9226), wake up well rested (Bet = 25, Clo = 0.0057, Str = 0.8491), and anxiety (Bet = 5, Clo = 0.0043, Str = 0.9697) among cancer survivors. The core symptoms, network structure, and global strength were invariant between time since diagnoses (< 2 years vs. ≥ 2 years) or between numbers of cancers (1 vs. ≥ 2), yet varied between the comorbidity group and non-comorbidity group (≥ 1 vs. 0). CONCLUSIONS: Fatigue would be a potential target for alleviating other symptoms through a negative feedback loop of other related symptoms of cancer survivors. In particular, cancer survivors with other chronic diseases should be the focus of attention and strengthen targeted intervention.

The effect of self-designed metabolic equivalent exercises on cancer-related fatigue in patients with gastric cancer: A randomized controlled trial.

AIMS: To investigate the effect of Self-designed Metabolic Equivalent Exercises (SMEE) on cancer-related fatigue in patients with gastric cancer. METHODS: 130 patients with gastric cancer admitted to Department of Oncology of a tertiary hospital in Shanghai were enrolled and assessed for eligibility. After excluding 1 patient who declined to participate, 129 eligible patients were randomly assigned into SMEE (n = 65) and control (n = 64) groups. The Revised Piper Fatigue Scale (RPFS) and EORTC QLQ-C30 Quality of Life Scale were used to measure cancer-caused fatigue and quality of life, respectively, in both groups at the first admission and after 3 months. RESULTS: After excluding patients who did not receive allocated intervention due to medical (n = 3) and personal (n = 2) reasons, those who were lost to follow-up (n = 3), and those who had discontinued intervention (n = 2), 119 patients (64 in the SMEE group and 55 in the control group) were included for analysis. There were no statistically significant differences in the RPFS or QLQ-C30 score between the two groups at baseline. After 3 months, the total RPFS score of the SMEE group was significantly lower than that of the control group (2.86 ± 1.75 vs. 4.65 ± 1.29, p = 0.009), with significant improvements in affective meaning (0.83 ± 0.92 vs. 1.13 ± 0.77, p = 0.044) and sensory (0.70 ± 0.71 vs. 1.00 ± 0.54, p < 0.001) subscales; in the SMEE group, QLQ-C30 scores in somatic (2.00 ± 0.27 vs. 1.31 ± 0.26, p < 0.001), emotional (2.67 ± 0.58 vs. 2.07 ± 0.48, p < 0.001), and social (3.23 ± 0.58 vs. 1.64 ± 0.51, p < 0.001) functioning were significantly higher than those in the control group, with significant improvements in fatigue (p < 0.001), nausea/vomiting (p = 0.014), shortness of breath (p < 0.001), constipation (p < 0.001), and diarrhea (p = 0.001) dimensions. CONCLUSION: The self-programmed metabolic equivalent manipulation as an exercise intervention could effectively reduce the degree of cancer-caused fatigue and improve quality of life in patients with gastric cancer.