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Background: Fatigue and sleep disorders are prevalent in cancer patients. Obstructive sleep apnea (OSA) commonly causes excessive daytime sleepiness (EDS) and fatigue. We hypothesize that treating cancer patients with OSA using positive airway pressure (PAP) will improve EDS and fatigue., Methods: A retrospective chart review of sleep clinic visits of cancer patients with newly diagnosed OSA was performed. Epworth Sleepiness Scale (ESS) and fatigue reported at baseline and within 6 months of starting PAP therapy were compared between PAP-adherent and PAP-non-adherent patients., Results: 65 cancer patients with OSA and ESS >10 were recommended PAP therapy, including 45 patients with fatigue. 29 patients pursued PAP therapy with 79% (n = 23) adherent at follow-up. The median baseline apnea hypopnea index (AHI) for OSA was 24.0 (interquartile range [IQR] 14.3, 32.3) and 23.8 (IQR 10.1, 42.8) events/hour among PAP-adherent and PAP-non-adherent patients, respectively (p = 0.90). Median baseline ESS was 14.0 (IQR 12.0, 17.0) among adherent and 17.0 (IQR 11.0, 17.3) among non-adherent patients (p = 0.73). The median ESS at follow-up of the adherent and non-adherent groups was 8.0 (IQR 6.0, 10.0) and 11.0 (IQR 8.0, 15.8), respectively (p = 0.08). Median ESS change was -5.0 (IQR -7.0, -4.0) in PAP adherent patients and -2.5 (IQR -5.25, -1.50) in PAP-non-adherent patients (p = 0.07). When the groups are examined separately, the median change in the PAP-adherent group was highly significant (p = 0.001), while the ESS median change in the PAP-non-adherent group was considerably less (p = 0.04). 17 out of the 21 PAP-adherent patients reporting fatigue at baseline indicated improvement at follow-up., Conclusions: PAP therapy for OSA in cancer patients improves EDS and fatigue. Larger studies are necessary to evaluate the efficacy of PAP in improving fatigue in this population., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Fatigue is one of the most disabling symptoms reported by people with multiple sclerosis. Although behavioural and pharmacological interventions might be partly beneficial, their combined effects have not been evaluated for multiple sclerosis fatigue, or examined with sufficient consideration of characteristics that might affect treatment response. In this comparative effectiveness research trial, we compared the effectiveness of cognitive behavioural therapy (CBT), modafinil, and their combination for treating multiple sclerosis fatigue., Methods: This randomised, analyst-blinded, parallel-arm, comparative effectiveness trial was done at two universities in the USA. Adults (aged ≥18 years) with multiple sclerosis and problematic fatigue (Fatigue Severity Scale [FSS] score ≥4) were randomly assigned (1:1:1), using a web-based treatment assignment system with minimisation, to receive CBT, modafinil, or both for 12 weeks. Statisticians were masked to group assignment, but participants, study neurologists, CBT interventionalists, and coordinators were not masked to treatment assignment. The primary outcome was the change in Modified Fatigue Impact Scale (MFIS) from baseline to 12 weeks, assessed using multiple linear regression, adjusted for age, sex, study site, anxiety, pain, baselines MFIS score, and physical activity. Analyses were done by intent to treat. The trial was registered with clinicaltrials.gov, NCT03621761, and is completed., Findings: Between Nov 15, 2018, and June 2, 2021, 336 participants were randomly assigned treatment (114 assigned to CBT, 114 assigned to modafinil, and 108 assigned to combination therapy). At 12 weeks, CBT (n=103), modafinil (n=107), and combination therapy (n=102) were associated with clinically meaningful within-group MFIS reductions of 15·20 (SD 11·90), 16·90 (15·90), and 17·30 (16·20) points, respectively. Change in MFIS scores from baseline to 12 weeks did not differ between groups: relative to combination therapy, the adjusted total mean difference in MFIS change score was 1·88 (95% CI -2·21 to 5·96) for CBT and 1·20 (-2·83 to 5·23) for modafinil. Most common adverse events for modafinil-containing treatment groups included insomnia (eight [7%] for modafinil and eight [7%] for combination therapy) and anxiety (three [3%] for modafinil and nine [8%] for combination therapy)., Interpretation: Modafinil, CBT, and combination therapy were associated with similar reductions in the effects of multiple sclerosis fatigue at 12 weeks. Combination therapy was not associated with augmented improvement compared with the individual interventions. Further research is needed to determine whether effects of these interventions on multiple sclerosis-related fatigue is influenced by sleep hygiene and sleepiness. No serious adverse events related to the study drug were encountered., Funding: Patient-Centered Outcomes Research Institute and National Multiple Sclerosis Society., Competing Interests: Declaration of interests TJB reports current or recent grants from the National Institutes of Health, the International Progressive MS Alliance, and the National MS Society, and an award from the Patient-Centered Outcomes Research Institute. She has received support from Michigan Humane for her research. She has received travel and meeting support from Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) and the American Academy of Neurology. She reports a patent held by the University of Michigan related to treatment of sleep apnoea. She receives material support, but no financial compensation, from Jazz Pharma for a National Institutes of Health-funded investigator-initiated trial. She holds unpaid service and leadership positions for the National MS Society and the ACTRIMS Program Committee. She has served as site principal investigator for trials of multiple sclerosis therapeutics sponsored by Genentech, Genyzme, and Novartis, but received no direct compensation for this work. KNA reports grants from the National Institutes of Health and the National MS Society and an award from the Patient-Centered Outcomes Research Institute. He has received royalties for licensing of materials to Actelion Pharmaceuticals. DME reports grants from the National Institutes of Health, the National MS Society, the National Institute of Disability, Independent Living, and Rehabilitation Research, Administration for Community Living, and the State of Washington, and an award from the Patient-Centered Outcomes Research Institute. She receives honoraria from the American Psychological Association for her role as Editor for the journal Rehabilitation Psychology. She has received royalties for licensing of materials to Actelion Pharmaceuticals. She serves without compensation in leadership and service roles for the National MS Society National Advisory Board on Medical Rehabilitation Research and on the editorial board for Archives of Physical Medicine and Rehabilitation. GvG reports grants from the Patient-Centered Outcomes Research Institute and the National MS Society and a contract from Novartis; she also serves on a National Institute for Neurological Disorders and Stroke board. TRV reports a grant from the National MS Society. ARR reports research effort support from the National Institutes of Health and travel and meeting support from ACTRIMS. RDC reports grants from the National Institutes of Health and the National MS Society, and an award from the Patient-Centered Outcomes Research Institute. He receives royalties from UpToDate for roles as an editor and author and is a paid Eli Lilly consultant (contract through University of Michigan). He reports patents and copyrighted material held by the University of Michigan for screening, diagnosis, and treatment of sleep disorders. He has held unpaid leadership positions on the board of directors and as treasurer and president elect for the International Pediatric Sleep Association. He serves on the advisory board of The Pajama Program. BMS reports grants from the National Institute of Health and Wings for Life Foundation. He has received travel support from ACTRIMS and International Society for Neuroimmunology for speaking engagements and programmatic activities. He serves as Secretary and Director for the ACTRIMS Program Committee. He has participated on a data and safety monitoring board for Data Safety Monitoring Committee, AACI Trailblazer Clinical Trial, Eli Lilly (2020–21). He holds filed or issued patents for an immune cell based neuroregenerative therapy, a treatment for sleep apnoea, and lymphoid chemokines, through the Ohio State University, University of Michigan, and University of Rochester, respectively. ALK reports grants from the National Institutes of Health, the National MS Society, the Craig H Neilsen Foundation, the National Institute of Disability, Independent Living, and Rehabilitation Research, Administration for Community Living, and the State of Michigan, and an award from the Patient-Centered Outcomes Research Institute. She receives honoraria from the American Psychological Association for her role as Editor for the journal Rehabilitation Psychology. She has received royalties for licensing of materials to Actelion Pharmaceuticals and she served as a paid consultant for Twill Health. She serves without compensation on committees for the United State Association for The Study of Pain and Society for Ambulatory Assessment and on the editorial boards for Journal of Pain and Arthritis Care & Research. RL, YTN, AJ, MH, MS, NL, YZ, and DC report no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Treatment of fatigue is important for many patients with multiple sclerosis (MS). While pharmacological options have not shown consistent benefit, psychological interventions offer another avenue of treatment. Cognitive behavioural therapy (CBT) involves strategies to change maladaptive cognition and illness behaviours that modulate how patients with MS respond to fatigue. The aim of this study was to perform a systematic review and meta-analysis to determine the effectiveness of CBT for the treatment of fatigue in patients with MS., Methods: Five databases (Cochrane Central Register of Controlled Trials, MEDLINE/PubMed, Embase, Emcare and PsycINFO) were searched up until 31 July 2023. Randomised controlled trials involving adult patients with MS and fatigue, comparing CBT with another intervention or usual treatment were included. Studies were required to measure fatigue severity and/or the impact of fatigue as the primary outcome(s). Each study was assessed for bias using the Cochrane Risk of Bias tool version 2. Studies with sufficient data were used for meta-analysis to quantify the short- and long-term effects of CBT on MS-related fatigue. The level of certainty provided by the body of evidence was evaluated using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework., Results: Eight studies were included in the review and six studies contributed to the meta-analysis. Most studies had a low overall risk of bias. CBT interventions differed in the number, duration and frequency of sessions, mode of delivery and therapist. There were significant short- (standardised mean difference (SMD) -0.58, 95% confidence interval (95%CI) -0.85 to -0.31, P-value < 0.0001) and long-term (SMD -0.36, 95%CI -0.52 to -0.19, P-value < 0.0001) effects supporting CBT. The evidence provided a low level of certainty for the short-term effect because of heterogeneity of results and possible publication bias, while there was high certainty for the long-term result., Conclusion: The study provides secondary evidence that CBT has moderate short-term and small long-term effects in reducing fatigue in patients with MS. CBT should be regarded as a viable evidence-based intervention, particularly in the absence of established alternatives. Future research should identify the ideal characteristics of a fatigue-specific CBT intervention, patient factors that predict treatment response and strategies to maintain initial improvements over time., Competing Interests: Declaration of competing interest The authors declare that no funding or research grants were received in the course of study, research or assembly of the manuscript., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Little is known about the quality of life (QOL) of patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). We compared QOL and associated factors in patients with MOGAD and aquaporin4 IgG (AQP4-IgG) positive neuromyelitis optica spectrum disorder (NMOSD)., Methods: This multicenter questionnaire study compared the QOL of 41 patients with MOGAD and 78 with AQP4-IgG positive NMOSD. Patients who were positive for AQP4-IgG or MOG antibodies were included. WHO Quality of Life Scale Brief Version was used to assess QOL in physical, psychological, social, and environmental domains. QOL, sleep quality, pain, fatigue, and depression were compared between the two groups. The factors associated with QOL in each group and the entire cohort were analyzed., Results: The proportion of patients with poor QOL was not significantly different between MOGAD (51.22 %) and AQP4-IgG positive NMOSD (58.97 %, p = 0.054). In the MOGAD group, the pain score (β=-1.032, p = 0.001) and depression score (β=-0.694, p = 0.007) were negatively associated with physical and psychological QOL, respectively. Sleep quality was negatively associated with physical (β=-1.506, p = 0.034) and psychological (β =-2.064, p = 0.033) QOL. When the entire cohort was analyzed, a positive MOG antibody was independently associated with worse psychological QOL (β=-8.998, p = 0.013) compared to positive AQP4-Ab after adjustment for sleep quality, depression, fatigue, and pain., Conclusions: The overall QOL of the patients of MOGAD was comparable to that of AQP4-IgG positive NMOSD. Patients with MOGAD were experiencing sleep disorder, fatigue, and depression at similar degrees to those of patients with AQP4-IgG positive NMOSD. Further consideration of sleep quality and psychological QOL is required to improve QOL in patients with MOGAD., Competing Interests: Declaration of competing interest None of the authors has any potential conflicts of interest to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Distance walking fatigability (DWF) in people with multiple sclerosis (pwMS) is defined as a decrease in the distance walking over time. However, declines in gait quality (i.e., gait quality fatigability- GQF) may occur independently or alongside DWF., Objective: i) to investigate how walking fatigability manifests and its prevalence in pwMS; ii) to describe the temporal pattern of the changes of specific gait characteristics during the 6-minute walking test (6MWT) METHODS: Eighty-eight pwMS (EDSS 4[0-6.5], 49[21-70] years) and 47 healthy controls (HC- 46[25-60] years) performed the 6MWT wearing inertial measurement units. Gait characteristics (stride length, sensor-based gait speed, cadence, double support, step duration, stance phase, step duration asymmetry, step duration variability, foot-strike, toe-off, and leg circumduction) and walking distance were recorded in 1-minute intervals. A fatigability index was calculated by comparing the last and first minute of the 6MWT to identify abnormal worsening based on cutoff scores. The manifestation of walking fatigability was counted. The temporal pattern of worsening of gait characteristics during the 6MWT was examined in pwMS exceeding the cutoff values, compared to pwMS without abnormal changes and HC, using a two-way ANOVA (group vs. minutes) RESULTS: Thirty-five pwMS presented both DWF and GQF, 2 presented isolated DWF, 27 presented isolated GQF, and 24 presented non-walking fatigability. PwMS having GQF presented worsening in gait characteristics (cadence, step duration, step duration variability, or toe-off angle) from minute 2 onwards of the 6MWT, while HCs and pwMS without abnormal changes stabilized gait from minute 2 towards the end of the 6MWT., Conclusion: Walking fatigability in pwMS manifests not only as a decrease in walking distance but also as changes in gait quality. Understanding changes in gait characteristics during walking can help tailor rehabilitation interventions., Competing Interests: Declaration of competing interest The Author (s) declare (s) that there is no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Depression affects around 50% of people with Multiple Sclerosis (pwMS) during their lifetime. PwMS are typically less physically active and spend twice as much time engaging in sedentary behaviour compared to the general population. Therefore, a better understanding of the factors associated with depression in pwMS, as well as the relationship between depression and sedentary behaviour and physical activity, is crucial for developing effective therapeutic strategies MS treatment. This study aimed to investigate whether the presence of depressive symptoms in pwMS is related to a longer duration of sedentary behaviour. Specially, the study assessed the relationship between depression and sedentary behaviour in women with relapsing-remitting MS (RRMS). The sample for this cross-sectional study consisted of 78 women, including 38 with relapsing-remitting MS (RRMS) (EDSS 1 to 3) and 40 healthy women. The study evaluated the depression and time in sedentary behaviour, levels of physical activity and subjective fatigue in three groups: women without MS (CG), women with MS and depression (MSD), and women with MS without depression (MSND). We found significant differences in sedentary behaviour time when comparing the group of women with MS to the group with MS and depression. The logistic regression analysis presents depression as a factor associated with sedentary behaviour in women with MS. This association became even stronger after adjustment in the multivariate model (odds ratio=1.62; 95% CI (1.13-2.64); p=0.021). Despite no differences in clinical disabilities (EDSS) or physical activity levels between the two MS subgroups (MSD and MSND), we observed a longer duration of sedentary behaviour among participants with MS and depression. There was no association with the level of physical activity. This suggests a relationship between depression and sedentary behaviour in women with MS, independent of the level of physical activity. Prolonged sedentary behaviour is a risk factor for other comorbidities, including cardiovascular disease, highlighting the importance of addressing both depression and sedentary behaviour in the management of MS. Studies that examine the amount of time pwMS spend in sedentary behaviour in various countries are crucial for developing more effective strategies tailored to different ethnicities and cultures., Competing Interests: Declaration of competing interest We have no conflict of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Alexithymia refers to difficulty identifying (DIF) and describing (DDF) feelings and externally oriented thinking (EOT). Its prevalence remains unknown in the radiologically isolated syndrome (RIS), the preclinical multiple sclerosis (MS) phase., Methods: Alexithymia was measured with the Toronto Alexithymia Scale (TAS-20) in 29 RIS and age and gender-matched healthy controls and relapsing-remitting (RR) MS with an EDSS <3. All participants completed evaluations of cognition (BCCOG-SEP), depression (Fast-BDI), fatigue (EMIF), and quality of life (SEP-59)., Results: The level of alexithymia was significantly different between the three groups, with the higher score in the RRMS group (mean score of 54.5, SD: 12,3) compared to RIS (mean score of 47.2, SD: 14.8) and in healthy controls (mean score of 41.9, SD:12.8). 34 % of RIS participants showed a pathological level of alexithymia. The proportions were 21.7 % in the healthy controls and 51.7 % in the RRMS-matched groups. The difference was mainly significant for the DIF factor, p<.001. No significant correlations were observed between alexithymia and the different measures of cognition. In the RIS group, alexithymia was strongly linked to the levels of depression and cognitive fatigue. Furthermore, alexithymia was related to decreased mental quality of life., Conclusion: The study revealed that one-third of subjects with radiologically isolated syndrome show signs of alexithymia. Interestingly, no cognitive measure was found to be correlated with the level of alexithymia, which is consistent with previous research findings. Alexithymia and mainly difficulty identifying feelings in RIS are associated with depression but also relate to cognitive fatigue and reduced mental quality of life. This could impact the daily interactions of RIS subjects., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Lifestyle changes have been demonstrated to impact pathophysiology in Multiple Sclerosis (MS). Various diet and exercise protocols have been reported to improve symptoms and function in persons with MS. Evidence is accumulating that interventions as early as possible in the disease course are warranted. The objective of this study was to investigate the effect of a remotely delivered lifestyle program focusing on specific diet and exercise recommendations in persons with early MS., Methods: MS patients, with disease diagnosis no more than 2 years prior, were recruited from the patient population of the MS clinic of the Pacific Neuroscience Institute. Participants followed recommendations for diet and exercise delivered via remote heath coaching. Each participant received 6 sessions with a health coach over a 12-week period. They were given parameters of a Mediterranean-type diet to follow, and specific and individualized recommendations about duration, intensity and type of exercise and physical activity. Outcome measures included Quality of Life (QOL), cognition (Symbol Digit Modalities Test, SDMT), fatigue (Multiple Sclerosis Fatigue Impact Scale, MFIS), fitness (estimated with Metabolic equivalents, METS) and other objective and patient reported outcomes (PRO). Changes in outcomes were analyzed using mixed effects general linear models and standardized pre-post differences.(Cohen's d) RESULTS: Fifteen persons with early (≤ 2 years) MS enrolled in the study, 14 of whom completed the study. We observed significant improvements in QOL (p = 0.02), SDMT (p = 0.006), fatigue(p = 0.005), fitness (p = 0.04), and other PRO and objective metrics at the end of the protocol compared to baseline. Adherence and patient satisfaction measures were high., Conclusions: Specific and individualized lifestyle recommendations can be effectively delivered remotely, and may produce improvement in symptoms and function in persons with early MS. Larger controlled trials of these interventions are warranted., Competing Interests: Declaration of competing interest NONE, (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: There is a lack of qualitative data on the negative effects of workplace stressors on the well-being of healthcare professionals in hospitals in Africa. It is unclear how well research methods developed for high-income country contexts apply to different cultural, social, and economic contexts in the global south., Methods: We conducted a qualitative interview-based study including 64 perioperative healthcare professionals across all provinces of Rwanda. We used an iterative thematic analysis and aimed to explore the lived experience of Rwandan healthcare professionals and to consider to what extent the Maslach model aligns with these experiences., Results: We found mixed responses of the effects on individuals, including the denial of burnout and fatigue to the points of physical exhaustion. Responses aligned with Maslach's three-factor model of emotional exhaustion, decreased personal accomplishment, and depersonalisation, with downstream effects on the healthcare system. Other factors included strongly patriotic culture, goals framed by narratives of Rwanda's recovery after the genocide, and personal and collective investment in developing the Rwandan healthcare system., Conclusions: The Rwandan healthcare system presents many challenges which can become profoundly stressful for the workforce. Consideration of reduced personal and collective accomplishment, of moral injury, and its diverse downstream effects on the whole healthcare system may better represent the costs of burnout Rwanda. It is likely that improving the causes of work-based stress will require a significant investment in improving staffing and working conditions., (Copyright © 2024 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Obstructive sleep apnea (OSA) is more common in patients with multiple sclerosis (MS) than in the general population, which suggests MS may predispose patients to OSA. However, the relationships between MS treatment, disease activity, disease severity, fatigue, and OSA are unknown., Objectives: To evaluate the connections between OSA risk, MS fatigue, and MS severity, controlling for well-established risk factors for OSA in the general population., Methods: We administered OSA and fatigue-related questionnaires to patients with MS and collected relevant demographic and clinical data. Then, we utilized multivariate logistic regression to examine relationships between OSA risk and MS disease severity., Results: We identified an inverse correlation between medication possession ratio (MPR) and high OSA risk. Statistical models also demonstrated a positive correlation between fatigue and nonwhite race with high OSA risk, controlling for male sex, younger age, and body mass index (BMI)., Conclusion: We identified disease-modifying therapy (DMT) underutilization, fatigue, and nonwhite race as predictors of high OSA risk in patients with MS. These findings support aggressive treatment of MS to avoid risk of comorbid OSA and MS-induced fatigue., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Long-COVID is a multisystem disease characterized by a varied presentation of symptoms. According to most recent research, the most common symptom of long-COVID is fatigue, which up to this date lacks a universally accepted definition. This study aimed to investigate neurocognitive and physical manifestations of neurological long-COVID, particularly fatigue and its relation with autonomic disfunction, cognitive impairment (known as, brain fog), and depressive symptoms. Furthermore, the study provided insights into predictors of fatigue in long-COVID., Methods: The included patients (n=141) were referred to the neuro-long-COVID ambulatory service of Trieste from 30 September 2021-02 March 2022. Patients were given self-reporting questionnaires to screen for fatigue, autonomic dysfunction, cognitive impairment and depressive symptoms. The questionnaires adopted for these conditions to be assessed were Fatigue Severity Scale (FSS), COMPASS-31, Prospective-Retrospective Memory Questionnaire (PRMQ), and Beck Depression Inventory (BDI). Participants were divided into two groups, fatigued and non-fatigued patients, based on FSS scoring (scores > 4.67 indicate fatigued patients). The questionnaire scores of the two groups were then compared., Results: Fatigued patients had significantly higher scores in COMPASS (p<0.001, Cohen's d=1.077), BDI (p<0.001, Cohen's d=0.862), and PRMQ ( p<0.001, Cohen's d=1.159). Furthermore, the multivariate regression analysis showed that predictors of fatigue in long-COVID were symptomatological burden in acute infection (OR=1.38, 95 % CI 1.020-1.887, p=0.037) and in long-COVID (OR=1.78, 95 % CI 1.133-2.2824, p=0.013), COMPASS-31>16 (OR=3.44, 95 % CI 1240-9.560, p=0.018) and BDI>15 (OR=5.1, 95 % CI 1.715-15.164, p=0.003)., Conclusion: This study showed associations between fatigue, dysautonomia and depression, as well as with symptom burden in acute and long-COVID., (Copyright © 2024. Published by Elsevier B.V.)

Background: Fatigue is the most commonly experienced symptom among people with multiple sclerosis (MS) and has the greatest impact in reducing quality of life. It is important to measure change in MS-related fatigue (MS-fatigue) in response to treatment, particularly the more recent disease modifying therapies (DMTs). To date there has been no systematic literature review of the patient reported outcome (PRO) tools used to measure MS- fatigue specifically in the context of DMTs., Methods: MEDLINE, Embase and Clinicaltrials.gov were searched from 01 January 2000 to 13 April 2021 to identify published studies of the treatment of MS with DMTs. Studies where MS-fatigue was measured as an outcome using a PRO tool were included in the review. Further literature searches were undertaken to provide information about the development and validation of each PRO tool., Results: 739 abstracts and 96 clinical trials were manually screened resulting in 68 articles for full text screening. 48 studies were identified for the review; 10 of these were RCTs that considered MS-fatigue as a secondary outcome (4 were Phase 3 trials). The PRO instruments used in the 10 RCTs were the Fatigue Scale for Motor and Cognitive Functions, Fatigue Impact Scale, Modified Fatigue Impact Scale, Fatigue Severity Scale, and Fatigue Symptoms and Impacts Questionnaire - Relapsing Multiple Sclerosis. The other 38 studies were all open-label, longitudinal, non-randomized studies and used the following PRO instruments in addition to those listed above: the Visual Analogue Scale for Fatigue, the Fatigue Descriptive Scale, Modified Fatigue Impact Scale (5 items) and the Würzburger Fatigue Inventory for MS. All these PRO tools were specifically developed for MS-fatigue. Of these 9 PRO tools, 7 were of good methodological quality according to the existing validation studies using the Consensus-based standards for the selection of health measurement instruments (COSMIN) check list and were used in the majority of the MS DMT studies (44/48, 92%). The median follow-up time from baseline to PRO measurement was 12 months (range 1-36 months). Most studies reported on MS fatigue in terms of its change from baseline and whether the change was statistically significant. 5 studies also reported what they considered to be a clinically meaningful difference., Conclusions: Although fatigue has the greatest impact on quality of life in people with MS, few studies have rigorously investigated the impact of DMTs on fatigue. Comparisons between study outcomes using different PRO tools is challenging due to the variety of psychometric constructs addressed by the questionnaires and differences in the recall period for fatigue symptoms and the measurement scale. Furthermore most of the PRO tools used to quantify MS-fatigue in studies of DMTs are descended from PRO tools developed during the 1990s before DMTs emerged and before widespread patient involvement in PRO development. New PRO tools should involve patients in their development as recommended by the US Food and Drug Administration and the validation process should consider the sensitivity of the PRO tool to change in fatigue over time or between groups., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: SS is a consultant for OPEN Health on independent contract. MA-T and HL are employees of Janssen Inc. The preparation of this manuscript was funded by Janssen., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The individual experience of fatigue and fatigability in individuals with Multiple Sclerosis (MS) can vary greatly, beyond the high prevalence of fatigue in MS. Although fatigue is known as a common symptom that affects and potentially limits individuals with MS, it has recently been determined that fatigability also causes consequences that limit individuals' daily lives. The purpose of this study was to compare the associations between self-reported levels of fatigue, measured fatigability, and estimates of functional capacity in people with MS and sex- and age-matched healthy individuals., Methods: Twenty-three individuals with Relapsing-Remitting MS (RRMS) diagnosis and 23 age- and sex-matched healthy individuals were included in the study. To examine the fatigability level Dynamic and Static Fatigue Index were used for gross and pinch-grip, and manual dexterity and functionality levels the Scale for the Assessment and Rating of Ataxia (SARA), Nine Hole Peg Test (NHPT), and Dexterity Questionnaire-24 (DextQ-24) were used. While the Fatigue Severity Scale (FSS) and Fatigue Impact Scale (FIS) were used to examine self-reported fatigue, the Beck Depression Inventory (BDI) was used to assess emotional status., Results: There was no difference between RRMS and healthy individuals in terms of fatigability levels (p > 0.05). While the relationship between Static and Dynamic Fatigue Index gross grip fatigability and FSS and FIS was not found to be statistically significant, the relationship between non-dominant side pinch grip Static Fatigue Index and FSS and FIS was significant. In addition, the relationship between the non-dominant side gross grip Static Fatigue Index and the DextQ-24 dressing and daily activities subsections, and the dominant side pinch grip Dynamic Fatigue Index and the television/compact disk/digital video disk subsection of DextQ-24 was significant (p < 0.05)., Conclusion: Fatigability was related to daily life upper limb use for gross grip and self-reported fatigue for pinch grip in individuals with RRMS. It was concluded that future studies focusing on hand fatigability could also consider manual dexterity and self-reported fatigue in individuals with MS from the early-stage. Clarifying the relationship of between fatigability and self-reported fatigue to functioning will allow clinicians to plan more appropriate and directed treatment approaches for individuals with RRMS., Trial Registration: ClinicalTrials.gov NCT05880745., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest for the research, authorship, and/or publication of this article. All study participants provided informed consent, and the appropriate ethics review boards approved the study design., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Physiological fitness, encompassing cardiorespiratory fitness (CRF) and body composition, are important markers of overall health, functional capacity, and quality of life in general and clinical populations. Characterizing fitness is important for the development of tailored interventions and strategies to optimize well-being across the spectrum of disability in multiple sclerosis (MS). While existing research has explored fitness in people with mild-to-moderate disability, there is a scarcity of data in people with advanced MS (Expanded Disability Severity Scale, EDSS≥7.0)., Objective: To characterize CRF and body composition and their associations with fatigue, quality of life, and function in individuals with advanced MS., Methods: Participants (n=18, mean age=60.7 years-old, median EDSS=7.5) underwent a cardiopulmonary exercise test and dual-energy X-ray absorptiometry scanning. Main outcomes included peak volume of oxygen uptake (V̇O 2peak ) and whole and regional body fat, lean mass, bone mineral content, and bone density. Symptoms of fatigue (Modified Fatigue Impact Scale, MFIS), quality of life (29-item MS Impact Scale, MSIS-29), and daily function (Late-Life Function and Disability Instrument, LLFDI) were collected., Results: Participants exhibited notably low CRF levels (V̇O 2peak =9.8 mL/min/kg) and poor body composition (lower lean mass, bone mineral content and density) compared to previous studies in the general population and in individuals with MS with lower disability. V̇O 2peak was most consistently associated with function in daily life (LLFDI scores, r s ≥0.637, p≤0.004)., Conclusion: These findings reinforce the potential importance of physiological fitness to preserve function in people with advanced MS., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest related to this manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Individuals with Multiple Sclerosis (MS) experience impairments in heat dissipation, compromising core temperature regulation during exercise., Objective: To examine the efficacy of combined head-and-neck cooling as administered via a commercially available cooling cap and neck wrap in mitigating increases in core temperature during exercise., Methods: On separate days, ten (7 females) adults (46.1 ± 11.6 years) with relapsing-remitting MS performed semi-recumbent cycling consisting of an incremental exercise bout to volitional fatigue in a temperate environment (23 °C, 50 % relative humidity) while undergoing head-and-neck cooling using a cooling cap and neck wrap maintained at 10 °C (COLD) or 24-26 °C (NEUTRAL). Prior to and following a 30-minute post-exercise recovery, functional capacity was assessed by a battery of tests consisting of a 2-minute walk test, Timed 25-Foot Walk test, sit-to-stand test, and Berg Balance Scale. Core (ingestible pill) and skin temperatures were recorded continuously. The level of fatigue was measured with questionnaires., Results: The duration of the incremental exercise test increased with the application of COLD (28.4 ± 5.1 min) versus NEUTRAL water (vs 20.8 ± 5.1 min) (p = 0.001) and was paralleled by a significant reduction in body temperatures (∼1 °C, p < 0.05). The distance covered during the 2-min walk test performed after the incremental exercise test increased with the COLD (176.5 ± 0.6 m), relative to the NEUTRAL condition (147.7 ± 43.5 m) (p = 0.01). Fatigue levels did not change between conditions., Conclusion: We show that head-and-neck cooling with cold water effectively enhances exercise tolerance and mitigates increases in core temperature during exercise in individuals with MS., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Iron deficiency and iron deficiency anaemia are frequently under-recognised in chronic conditions with non-specific symptoms, including fatigue. This study aimed to assess the prevalence of iron deficiency with or without anaemia in chronic pain patients, and the association between iron deficiency status, fatigue and health-related quality of life. Eighty-two patients attending chronic pain outpatient appointments were recruited into this cross-sectional study. Iron studies and haemoglobin were determined from venous blood samples. Participants' health-related quality of life was assessed with the 36-item short form survey and fatigue with the functional assessment of chronic illness therapy fatigue scale. Iron deficiency was prevalent in 58.8% of patients and 2.5% met the criteria for iron deficiency anaemia. There was no significant association between iron deficiency status and the functional assessment of chronic illness therapy fatigue scale score or 36-item short form survey domain scores. There was a high prevalence of iron deficiency in this group of chronic pain patients, while the prevalence of iron deficiency anaemia was low. There was no statistically significant association found between iron deficiency status and fatigue or quality of life measures., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: The COVID-19 pandemic, caused by SARS-CoV-2, has led to long-term health issues known as post-COVID-19 condition, including fatigue and cognitive disruptions. Despite its recognition as a public health concern, the efficacy of therapeutic interventions, especially in neurological rehabilitation, remains unclear. This study examines how treatment expectations are associated with psychological and physical outcomes in post-COVID-19 condition neurological rehabilitation., Methods: In an observational cohort study 61 patients with confirmed post-COVID-19 condition were included. Baseline (T0) data on treatment and side effect expectations were collected, before participants underwent a 4-6 week multidisciplinary rehabilitation program. Primary outcome was illness-related disability (Pain Disability Index). Secondary outcomes included depressive symptoms (PHQ-9), anxiety levels (GAD-7), functional status (PCFS), fatigue (CFS), and physical fitness (6MWT). Regression models analyzed the associations of baseline expectations with outcomes at the end of rehabilitation (T1) and three months post-rehabilitation (T2)., Results: After adjusting for multiple testing, higher baseline side-effect expectations were associated with greater illness-related disability (β = 0.42, p = 0.007), reduced physical fitness (β = - 0.24, p = 0.04), and more somatic symptoms (β = 0.33, p = 0.006) at follow-up (T2). Positive treatment expectations were associated with poorer functional status (β = 0.35, p = 0.011) at T2., Conclusion: This study highlights the associations of side-effect expectations with post-COVID-19 condition rehabilitation outcomes. Higher side-effect expectations were associated to poorer outcomes, indicating a nocebo effect. Surprisingly, positive expectations were linked to worse outcomes, possibly due to unrealistic optimism. Managing patient expectations realistically and addressing side-effect concerns seems crucial for optimizing rehabilitation outcomes., Competing Interests: Declaration of competing interest SS reports research funding (no personal honoraria) from the German Research Foundation and the German Heart Foundation/German Foundation of Heart Research. WR declares to have received honoraria from Boehringer Ingelheim for workshops on Post Covid, and royalties from book publishers. All other authors report to have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier Inc.)

Objective: Ultramarathon runners are a unique patient population who have been shown to have a lower rate of severe chronic medical conditions. This study aimed to determine the effect that COVID-19 infection has had on this population and their running behavior., Design: The Ultrarunners Longitudinal TRAcking (ULTRA) Study is a large longitudinal study of ultramarathon runners. Questions on health status, running behavior, and COVID-19 infection were included in the most recent survey., Setting: Community survey., Participants: Seven hundred thirty-four ultramarathon runners participated in the study., Interventions: None., Main Outcome Measures: Personal, exercise, and COVID-19 infection history., Results: 52.7% of study participants reported having been symptomatic from a COVID-19 infection, with 6.7% testing positive multiple times. Participants required a total of 4 days of hospitalization. The most common symptoms included fever (73.6%), fatigue (68.5%), sore throat (68.2%), runny nose (67.7%), and cough (67.4%). Cardiovascular symptoms, which are of particular interest in the running population, included shortness of breath (46.3%), tachycardia (44.7%), chest pain (36.2%), and wheezing (33.3%). A total of 50 subjects (6.8%) reported long COVID (symptoms lasting more than 12 weeks)., Conclusions: Severe COVID-19 infection has been rare in this population of ultramarathon runners, although symptomatic infection that affects running is common. To support the well-being of this group of highly active athletes, clinicians should appreciate that cardiovascular symptoms are common and the long-term significance of these symptoms in runners is unknown., Level of Evidence: Level 2 prospective study., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Depression is a pervasive symptom in patients with gynecological cancer undergoing chemotherapy., Objectives: Purposes were to identify subgroups of patients with distinct depression profiles and evaluate for differences in demographic and clinical characteristics, severity of common symptoms, and quality of life (QOL) outcomes among these subgroups., Methods: Patients with gynecological cancer (n = 231) completed the Center for Epidemiologic Studies-Depression Scale 6 times over 2 cycles of chemotherapy. All of the other measures were completed prior to the second or third cycle of chemotherapy. Latent profile analysis was done to identify the distinct depression profiles. Differences were evaluated using parametric and nonparametric tests., Results: Three distinct profiles were identified: low (60.1%), high (35.1%), and very high (4.8%). Compared with low class, the other 2 classes had lower functional status and were more likely to self-report a diagnosis of depression. Patients in the 2 worse profiles reported a higher comorbidity burden, higher levels of trait and state anxiety, sleep disturbance, and fatigue, as well as lower levels of cognitive function and poorer QOL. State and trait anxiety, evening fatigue, and sleep disturbance scores exhibit a "dose-response effect" (ie, as the depression profile worsened, the severity of these symptoms increased)., Conclusions: Almost 40% of our sample experienced high or very high levels of depression across 2 cycles of chemotherapy., Implications for Practice: Clinicians can use the identified risk factors to identify high patients risk and provide tailored psychological interventions aimed to decrease symptom burden and prevent decrements in QOL., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The multifaceted nature of Fibromyalgia syndrome (FM) symptoms has been explored through clusters analysis., Objective: To synthesize the cluster research on FM (variables, methods, patient subgroups, and evaluation metrics)., Methods: We performed a systematic review following the PRISMA recommendations. Independent searches were performed on PubMed, Embase, Web of Science, and Cochrane Central, employing the terms "fibromyalgia" and "cluster analysis". We included studies dated to January 2024, using the cluster analysis to assess any physical, psychological, clinical, or biomedical variables in FM subjects, and descriptively synthesized the studies in terms of design, cluster method, and resulting patient profiles., Results: We included 39 studies. Most with a cross-sectional design aiming to classify subsets based on the severity, adjustment, symptomatic manifestations, psychological profiles, and response to treatment, based on demographic and clinical variables. Two to four different profiles were found according to the levels of severity and adjustment to FMS. According to symptom manifestation, two to three clusters described the predominance of pain versus fatigue, and thermal pain sensitivity (less versus more sensitive). Other clusters revealed profiles of personality (pathological versus non-pathological) and psychological vulnerability (suicidal ideation). Additionally, studies identified different responses to treatment (pharmacological and multimodal)., Conclusion: Several profiles exist within FMS population, which point out to the need for specific treatment options given the different profiles and an efficient allocation of healthcare resources. We notice a need towards more objective measures, and the validation of the cluster results. Further research might investigate some of the assumptions of these findings, which are further discussed in this paper., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The objective was to determine the prevalence and clinical correlates of nonmotor symptoms in Parkinson's disease patients in movement disorders outpatient clinics., Methods: We enrolled all consecutive PD patients who visited our movement disorders outpatient clinics between January and December 2023; and agreed to participate in the study. In addition to the evaluation of demographic and clinical features, clinical scales, including the MDS-UPDRS, NMSS, and FOOGQ, were performed., Results: Overall, we enrolled 163 PD subjects with a mean age of 63.9 ± 10.4 (F/M = 27/136). The disease duration was 3.5 (20) y [median (range)]. The median score of the NMSS was 41 points. The NMSs burden levels were severe in 25.2%, and very severe in 25.2% of the subjects. The subitems with the highest scores were sleep/fatigue, mood/cognition, urinary, and miscellaneous. The analyses within the patient group with newly diagnosed PD also revealed high NMSS scores. Comparisons of the NMSS between distinct PD stages revealed greater NMSS scores in the severe stage than in the mild stage ( p  = 0.001). Correlation analyses between the clinical scores and the NMSS scores revealed positive correlations between the NMSS scores and the scores on all the clinical scales including the MDS-UPDRS 1-4, and FOGQ., Conclusion: We reported the first data regarding the NMS burden in PD patients from Turkey. We found a high prevalence and severity of various domains of NMSs, most of which were sleep/fatigue, mood/cognition, urinary, and miscellaneous. More than half of the patients had severe to very severe NMS burden. Although NMSs were more common severe-stage disease, they were also prevalent in the subgroup with newly diagnosed patients.

Background: Fatigue is a prominent symptom of heart failure (HF). However, underlying mechanisms remain poorly understood. Fluid volume status has been suggested as a physiologic mechanism of HF-related fatigue. Serum osmolality may fluctuate with changes in volume status associated with neurohormonal dysregulation. The relationship of fatigue to serum osmolality has not been assessed in adults with HF., Objectives: Describe the relationship between serum osmolality and fatigue in adults with HF., Methods: We analyzed two waves of cross-sectional data from the National Health and Nutrition Examination Survey (2015-2016 and 2017-2018). Adults who self-reported having HF without select co-morbid conditions known to contribute to fatigue were included. Data were weighted to provide US national estimates, and complex sample design used for analyses. Sequential logistic regression was used to isolate the effect of serum osmolality on the odds of having fatigue., Results: Data from the sample represented 1.4 million Americans with HF (58.5 % male; median age 68 years), of whom 1,001,589 (67.9 %) reported fatigue. Participants with fatigue had lower serum osmolality compared to those without fatigue (t = -3.04, p = .009). Higher serum osmolality was associated with 8.8 % lower odds of experiencing fatigue when controlling for sex and body mass index (OR = 0.912, p = .007, CI 0.857 - 0.972)., Conclusions: HF-related fatigue is associated with lower serum osmolality. Low serum osmolality may indicate excess volume and the presence of a heightened neurohormonal response, both of which may influence fatigue. Alternatively, serum osmolality may directly affect other physiologic changes that may contribute to fatigue., Competing Interests: Declaration of competing interest All authors declare no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work; and no other relationships or activities that could appear to have influenced the submitted work. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Objectives: Cognitive impairment (CI) in multiple sclerosis (MS) is frequent and determined by a complex interplay between inflammatory and neurodegenerative processes. We aimed to investigate whether CSF parvalbumin (PVALB), measured at the time of diagnosis, may have a prognostic role in patients with MS., Methods: In this cohort study, CSF analysis of PVALB and Nf-L levels was performed on all patients at diagnosis (T0) and combined with physical, cognitive, and MRI assessment after an average of 4 years of follow-up (T4) from diagnosis. Cognitive performance was evaluated with a comprehensive neuropsychologic battery: both global (cognitively normal, CN, mildly CI, mCI, and severely CI, sCI) and domain cognitive status (normal/impaired in memory, attention/information processing speed, and executive functions) were considered. Cortical thickness and gray matter volume data were acquired using 3T MRI scanner., Results: A total of 72 patients with MS were included. At diagnosis, PVALB levels were higher in those patients who showed a worsening physical disability after 4 years of follow-up ( p = 0.011). CSF PVALB levels were higher in sCI patients than in CN ( p = 0.033). Moreover, higher PVALB levels significantly correlated with worse global cognitive ( p = 0.024) and memory functioning ( p = 0.044). A preliminary clinical threshold for PVALB levels at diagnosis was proposed (2.57 ng/mL), which maximizes the risk of showing CI (in particular, sCI) at follow-up, with a sensitivity of 91% (specificity 30%). No significant results were found for these associations with Nf-L. In addition, patients with higher levels of PVALB at diagnosis showed higher cognitive ( p = 0.024) and global fatigue ( p = 0.043) at follow-up. Finally, higher PVALB levels also correlated significantly with more pronounced CTh/volume at T4 in the inferior frontal gyrus ( p = 0.044), postcentral gyrus ( p = 0.025), frontal pole ( p = 0.042), transverse temporal gyrus ( p = 0.008), and cerebellar cortex ( p = 0.041) and higher atrophy (change T0-T4) in the right thalamus ( p = 0.038), pericalcarine cortex ( p = 0.009), lingual gyrus ( p = 0.045), and medial frontal gyrus ( p = 0.028)., Discussion: The significant association found between parvalbumin levels in the CSF at diagnosis and cognitive, clinical, and neuroradiologic worsening after 4 years of follow-up support the idea that parvalbumin, in addition to Nf-L, might represent a new potential prognostic biomarker, reflecting MS neurodegenerative processes occurring since early disease stages.

Background: Newly diagnosed breast cancer patients experience symptoms that may affect their quality of life, treatment outcomes, and survival. Preventing and managing breast cancer-related symptoms soon after diagnosis is essential. The purpose of this study was to investigate the associations between health-related fitness (HRF) and patient-reported symptoms in newly diagnosed breast cancer patients., Methods: This study utilized baseline data from the Alberta Moving Beyond Breast Cancer Cohort Study that were collected within 90 days of diagnosis. HRF measures included peak cardiopulmonary fitness (peak volume of oxygen consumption (VO 2peak )), maximal muscular strength and endurance, flexibility, and body composition. Symptom measures included depression, sleep quality, and fatigue. Adjusted multivariable logistic regression was performed for analyses., Results: Of 1458 participants, 51.5% reported poor sleep quality, 26.5% reported significant fatigue, and 10.4% reported moderate depression. In multivariable-adjusted models, lower relative VO 2peak was independently associated with a greater likelihood of all symptom measures, including moderate depression (p < 0.001), poor sleep quality (p = 0.009), significant fatigue (p = 0.008), any symptom (p < 0.001), and multiple symptoms (p < 0.001). VO 2peak demonstrated threshold associations with all symptom measures such that all 3 lower quartiles exhibited similar elevated risk compared to the highest quartile. The strength of the threshold associations varied by the symptom measure with odds ratios ranging from ∼1.5 for poor sleep quality to ∼3.0 for moderate depression and multiple symptoms. Moreover, lower relative upper body muscular endurance was also independently associated with fatigue in a dose-response manner (p = 0.001), and higher body weight was independently associated with poor sleep quality in an inverted U pattern (p = 0.021)., Conclusion: Relative VO 2peak appears to be a critical HRF component associated with multiple patient-reported symptoms in newly diagnosed breast cancer patients. Other HRF parameters may also be important for specific symptoms. Exercise interventions targeting different HRF components may help newly diagnosed breast cancer patients manage specific symptoms and improve outcomes., (Copyright © 2024. Production and hosting by Elsevier B.V.)

Background: Physical activities performed under free-living conditions that are unsupervised in the home or community have the potential to modulate non-motor symptoms in people with Parkinson's disease., Objective: This systematic review investigates the relationships between physical activities performed in free-living conditions and non-motor symptoms in people with Parkinson's disease: cognition, anxiety, apathy, depression, sleep disturbances, fatigue, and pain., Data Sources: A database search was performed on Scopus, Web of Science, Ovid (PsycINFO), CINAHL, PubMed, and ProQuest (Health and Medicine)., Review Methods: Observational studies published from 2000 to 2024 that examined the relationships between physical activity and non-motor symptoms were included. The methodological quality of reports was evaluated using critical appraisal checklists appropriate to the study design. Where appropriate, a meta-analysis was conducted to combine data from the included articles., Results: A total of 14 articles met the criteria and used various tools to evaluate non-motor symptoms and physical activity. Meta-analyses showed that people with Parkinson's who are more physically active have better global cognition [ β ranged from 0.12 to 0.28; p  = 0.00-0.02] and less affective disorders [ β -0.20, p  = 0.00]. Increased physical activity levels were also associated with better sleep quality ( n  = 1) and less chronic pain ( n  = 1). The overall methodological quality of the included articles was considered high., Conclusion: Engagement in increased levels of physical activities performed under free-living conditions is associated with better cognition and less anxiety, apathy, and depression in people with Parkinson's disease., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: We aimed to generate a model of cancer-related fatigue (CRF) of clinical importance 2 years after diagnosis of breast cancer building on clinical and behavioral factors and integrating pre-treatment markers of systemic inflammation., Patients and Methods: Women with stage I-III hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer were included from the multimodal, prospective CANTO cohort (NCT01993498). The primary outcome was global CRF of clinical importance [European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 ≥40/100] 2 years after diagnosis (year 2). Secondary outcomes included physical, emotional, and cognitive CRF (EORTC QLQ-FA12). All pre-treatment candidate variables were assessed at diagnosis, including inflammatory markers [interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, interferon γ, IL-1 receptor antagonist, tumor necrosis factor-α, and C-reactive protein], and were tested in multivariable logistic regression models implementing multiple imputation and validation by 100-fold bootstrap resampling., Results: Among 1208 patients, 415 (34.4%) reported global CRF of clinical importance at year 2. High pre-treatment levels of IL-6 (quartile 4 versus 1) were associated with global CRF at year 2 [adjusted odds ratio (aOR): 2.06 (95% confidence interval [CI] 1.40-3.03); P = 0.0002; area under the receiver operating characteristic curve = 0.74]. Patients with high pre-treatment IL-6 had unhealthier behaviors, including being frequently either overweight or obese [62.4%; mean body mass index 28.0 (standard deviation 6.3 kg/m 2 )] and physically inactive (53.5% did not meet World Health Organization recommendations). Clinical and behavioral associations with CRF at year 2 included pre-treatment CRF [aOR versus no pre-treatment CRF: 3.99 (95% CI 2.81-5.66)], younger age [aOR per 1-year decrement: 1.02 (95% CI 1.01-1.03)], current tobacco smoking [aOR versus never: 1.81 (95% CI 1.26-2.58)], and worse insomnia or pain [aOR per 10-unit increment: 1.08 (95% CI 1.04-1.13), and 1.12 (95% CI 1.04-1.21), respectively]. Secondary analyses indicated additional associations of IL-2 [aOR per log-unit increment: 1.32 (95% CI 1.03-1.70)] and IL-10 [0.73 (95% CI 0.57-0.93)] with global CRF and of C-reactive protein [1.42 (95% CI 1.13-1.78)] with cognitive CRF at year 2. Emotional distress was consistently associated with physical, emotional, and cognitive CRF., Conclusions: This study proposes a bio-behavioral framework linking pre-treatment systemic inflammation with CRF of clinical importance 2 years later among a large prospective sample of survivors of breast cancer., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Mind-body therapies (MBTs) have gained popularity among patients with cancer as a supportive therapy. To date, no systematic reviews have assessed the effect of MBTs on the health outcomes in women with gynecological cancer., Objective: This systematic review and meta-analysis aimed to synthesize the effectiveness of MBTs on quality of life, anxiety, depression, cancer-related pain, and fatigue among women with gynecological cancer., Methods: We searched and screened randomized controlled trials in 7 databases, trial registries, and gray literature from the databases' inception to December 2021. Data were extracted from eligible studies, with each study's quality assessed using the Cochrane risk-of-bias tool. Meta-analyses were conducted using RevMan 5.4. Sensitivity and subgroup analyses were performed. The quality of evidence across the studies was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach., Results: Nine trials were included. Statistically significant effects of MBTs on depression (standardized mean difference, -0.56; 95% confidence interval, -1.01 to -0.11; P = .01), pain (standardized mean difference, -1.60; 95% confidence interval, -3.14 to -0.07; P = .04), and fatigue (standardized mean difference, -1.17; 95% confidence interval, -2.16 to -0.18; P = .02) were observed, but not on quality of life and anxiety. The quality of evidence was low due to the high risks of bias and high heterogeneity among the studies., Conclusions: Mind-body therapies were effective in reducing depression, pain, and fatigue of women with gynecological cancer. However, the low quality of the evidence implies the need for more future studies with better methodologies., Implications for Practice: Mind-body therapies may be used as an additional strategy to help manage depressive mood, pain, and fatigue among women with gynecological cancer., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The purpose of this study is to examine the national impact of workplace factors during the SARS-CoV-2 pandemic on mental health experienced by non-physician healthcare workers (HCWs)., Methods: This study consisted of an online sample of non-physician HCWs across the United States, including nurses, medical assistants, and physician assistants. The survey consisted of 93 questions, which included the Perceived Stress Scale, the Center for Epidemiological Studies-Depression (CESD-10) scale, questions about COVID-19 vaccination, sources of trusted information, and questions about work environment and training during the COVID-19 pandemic. Descriptive statistics were used to evaluate associations., Results: In the final sample ( N = 220), (81.8%) reported receiving at least one dose of a COVID vaccine. Most respondents trusted the CDC's information on the SARS-CoV-2 virus and COVID-19 disease. Several workplace-related factors that occurred during the pandemic were associated with moderate to high levels of perceived stress, fatigue, and higher risk of developing depression. In particular, concerns about exposing others, experiencing discrimination related to their jobs, and caring for patients who died from COVID-19 were associated with increased perceived stress, depression, and fatigue., Conclusions: The importance of planning by healthcare facilities should include planning for workplace factors associated with poor mental health among all HCWs.

Objectives: Following the declaration of the pandemic, students' education has to be done at a distance due to the COVID-19 pandemic. This study evaluated the association of university students' COVID-19 phobia, pain severity, sleep quality, physical activity, fatigue levels, and quality of life on students' achievement., Methods: This cross-sectional survey was conducted by including 353 students from the university faculty of health sciences. The Pain Quality Assessment Scale was used to assess pain, the Fatigue Severity Scale to evaluate fatigue, the COVID-19 Phobia Scale to assess fear of disease, the International Physical Activity Questionnaire Short Form to evaluate physical activity level, and the Jenkins Sleep Scale to assess sleep quality, The Short Form-36 to determine the quality of life, and Online Learning Systems Acceptance Scale to evaluate satisfaction with distance education. Multiple linear regression and path analysis were conducted to identify factors associated with academic achievement., Results: It was found that age ( B = 0.045; P = 0.040), BMI ( B = -0.200; P = 0.004), and physical ( B = 0.128; P = 0.008), psychological ( B = 0.057; P = 0.012) and social ( B = 0.189; P = 0.018) domains of quality of life were associated with the level of achievement., Conclusions: Precautions must be taken to improve students' academic achievement and quality of life in preparing for the future against infectious and epidemic diseases.

Many patients with fatigue do not visit a physician. In patients who do consult the general practitioner, the cause of their fatigue is explained in about a quarter: 8 percent has a somatic cause while psychosocial causes explain 16 percent. In about three quarters the cause of fatigue remains unexplained. Because of the low prevalence of somatic causes the general practitioner will be reluctant to perform additional examinations but a thorough physical examination is essential. In patients with a longer duration of fatigue (> 6 months) it is indicated to expand inquiries. This starts with extending history taking in the direction of consanguinity and hereditary diseases. More comprehensive blood tests and investigation of sleep are important further steps. Referral to a specialist is essential as specialists are more familiar with scripts of rare diseases. The prognosis of longer lasting fatigue is bad, especially in the case of fatigue meeting criteria for ME/CFS. Treatment of longer lasting fatigue could compromise of psycho-education, exercise and specific therapies for sleeping disorders.

Background: Post-COVID-19 syndrome has affected millions of people, with rehabilitation being at the center of non-pharmacologic care. However, numerous published studies show conflicting results due to, among other factors, considerable variation in subject characteristics. Currently, the effects of age, sex, time of implementation, and prior disease severity on the outcomes of a supervised rehabilitation program after COVID-19 remain unknown., Methods: This was a non-randomized case-control study. Subjects with post-COVID-19 sequelae were enrolled. Among study participants, those who could attend an 8-week, supervised rehabilitation program composed the intervention group, whereas those who couldn't the control group. Measurements were collected at baseline and 8 weeks thereafter., Results: Study groups ( N = 119) had similar baseline measurements. Participation in rehabilitation ( n = 47) was associated with clinically important improvements in the 6-min walk test (6MWT) distance, adjusted (for potential confounders) odds ratio (AOR) 4.56 (95% CI 1.95-10.66); 1-min sit-to-stand test, AOR 4.64 (1.88-11.48); Short Physical Performance Battery, AOR 7.93 (2.82-22.26); health-related quality of life (HRQOL) 5-level EuroQol-5D (Visual Analog Scale), AOR 3.12 (1.37-7.08); Montreal Cognitive Assessment, AOR 6.25 (2.16-18.04); International Physical Activity Questionnaire, AOR 3.63 (1.53-8.59); Fatigue Severity Scale, AOR 4.07 (1.51-10.98); Chalder Fatigue Scale (bimodal score), AOR 3.33 (1.45-7.67); Modified Medical Research Council dyspnea scale (mMRC), AOR 4.43 (1.83-10.74); Post-COVID-19 Functional Scale (PCFS), AOR 3.46 (1.51-7.95); and COPD Assessment Test, AOR 7.40 (2.92-18.75). Time from disease onset was marginally associated only with 6MWT distance, AOR 0.99 (0.99-1.00). Prior hospitalization was associated with clinically important improvements in the mMRC dyspnea scale, AOR 3.50 (1.06-11.51); and PCFS, AOR 3.42 (1.16-10.06). Age, sex, and ICU admission were not associated with the results of any of the aforementioned tests/grading scales., Conclusions: In this non-randomized, case-control study, post-COVID-19 rehabilitation was associated with improvements in physical function, activity, HRQOL, respiratory symptoms, fatigue, and cognitive impairment. These associations were observed independently of timing of rehabilitation, age, sex, prior hospitalization, and ICU admission., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2024 by Daedalus Enterprises.)

Background: Whether hours on shift might impact adaptation to night shift work is still controversial., Methods: We conducted a pooled analysis of two studies, including 170 hospital nurses working night shifts, 116 from a United Kingdom study working 12-hour rotating shifts, and 54 from Italy working 8-hour shifts. Both studies used the Epworth Sleepiness Scale (ESS) to detect sleepiness during routine daytime activities as an indicator of fatigue. We compared the prevalence of daytime sleepiness, as indicated by an ESS score≥11, resulting from either shift work schedule. We used logistic regression to calculate the risk of daytime sleepiness associated with 12-hour vs. 8-hour nightshifts, adjusting by age, sex, and parenting children aged≤4., Results: When comparing similar work circumstances, nightshifts prolonged to 12 hours did not increase the risk of daytime sleepiness compared to 8 hours (OR=0.9, 95% CI 0.32, 2.59)., Conclusions: Our results suggest that 12-hour rotating nightshifts with additional rest days and 8-hour rotating shift schedules do not differ in their impact on daytime sleepiness. Further research is warranted on what strategies might effectively contrast fatigue, circadian misalignment, and the related metabolic changes leading to adverse health outcomes, including cancer.

Purpose: Individuals diagnosed with cancer experience multiple inter-related short- and long-term side effects. Chief among such symptomology is cancer-related fatigue (CRF), which, if left unmanaged, can become chronic and result in increased disability and healthcare utilization. A growing number of self-report scales have been developed to measure CRF symptoms based on various theoretical conceptualizations with the aim of promoting targeted assessment and intervention efforts. It may be, however, unwise to assume that the various measures are conceptually similar (i.e., that they assess for the same constructs). Accordingly, we aimed to characterize item content among nine self-report scales, using a Jaccard index to quantify content overlap among scales., Methods: We characterized construct assessment among nine self-report scales recommended to assess CRF by a recent clinical practice guideline, and used a Jaccard index to quantify content overlap among scales., Results: Analysis of 208 items across nine rating scales resulted in 20 distinct symptoms of CRF assessed. The most common symptoms were energy level (captured in all nine scales), cognitive function, impaired task performance (in eight scales), sleepiness, and physical function (in seven scales). Mean overlap among all scales was low (Jaccard index = 0.455). Only one construct (duration of fatigue; 5.0%) was captured by a single scale, and one symptom (energy level; 5.0%) was common across all scales. The PFS, MFSI, and BFI each captured at least one symptom from each of the NCCN domains of CRF., Conclusion: CRF scales are heterogeneous in the content they measure, critically impairing integration of knowledge across studies using disparate scales. Future work is urgently needed to build more integrated theoretical and/or computational models of CRF based on relevant mechanisms., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Chronic Kidney Disease (CKD) is a progressive disorder that often leads to End-Stage Renal Disease (ESRD), necessitating hemodialysis (HD) treatment. Fatigue is a prevalent and debilitating symptom among HD patients, significantly affecting their quality of life. Recreational Therapy (RT) is a therapeutic recreational service designed to maintain and restore a person's level of performance and independence in daily activities. This study aimed to evaluate the effect of a smartphone-based recreational therapy intervention on fatigue in hemodialysis patients., Methods: This randomized controlled trial was conducted on HD patients at a hospital in Mashhad, Iran. The intervention group received a custom-designed recreational therapy mobile application, including music, comedy, exercise, and educational content. The control group received standard care. Fatigue was assessed using the Multidimensional Fatigue Inventory (MFI-20) before and after the 30-day intervention., Results: A total of 72 patients (36 per group) participated in the study. The intervention group demonstrated a significant reduction in overall fatigue scores and improvements across various fatigue dimensions, including general fatigue, physical fatigue, mental fatigue, reduced activity, and reduced motivation, compared to the control group (p < 0.001)., Conclusion: The smartphone-based recreational therapy intervention effectively reduced fatigue in hemodialysis patients. This approach could be a valuable complementary strategy for managing fatigue in this population. Further research is needed to explore the long-term sustainability of these benefits and the intervention's impact on other patient-reported outcomes., Trial Registration: This study was registered in the Iranian Registry of Clinical Trials (no. IRCT20220803055608N1) on 29/08/2022., (© 2024. The Author(s).)

Objectives: To investigate whether a combination of general health (Visual Analogue Scale (VAS)), Health Assessment Questionnaire-Disability Index (HAQ-DI), pain (VAS/Numerical Rating Scale (NRS)), quality of life (EQ-5D), fatigue (VAS/NRS) and presenteeism (0%-100% productivity loss) could aid as a screening tool to detect active disease in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA)., Methods: RA patients from the tREACH trial and TARA trial (n=683) and PsA patients from the DEPAR cohort (n=525) were included. The association of a deterioration in the aforementioned patient-reported outcome measure (PROM) scores between two consecutive visits and having active disease was assessed. Active disease was defined as a change from disease activity score (DAS) ≤2.4 to DAS >2.4 in RA or Disease Activity Index in Psoriatic Arthritis (DAPSA) ≤14 to DAPSA >14 in PsA. The area under the curve (AUC) of the sum score of deteriorated PROMs was evaluated., Results: 4594 RA and 1154 PsA visits were evaluated and active disease occurred in 358 (8%) RA and 177 (15%) PsA visits. In both RA and PsA, a deterioration in general health (VAS), HAQ-DI, EQ-5D and pain (VAS/NRS) was significantly associated with active disease. The combination of these PROMs showed acceptable to excellent discriminative ability (RA AUC=0.76, PsA AUC=0.85). If a cut-point of ≥1 deteriorated PROMs is used, 40% of the visits in which RA patients have remission or low disease activity are correctly specified (specificity of 40%), while 10% of visits with active disease are overlooked (sensitivity of 90%). In PsA, these percentages are 41% and 4%, respectively., Conclusion: A combination of general health, HAQ-DI, EQ-5D and pain could aid as a screening tool for active disease in patients with RA and PsA. These data could help facilitate remote monitoring of RA and PsA patients in the future., Trial Registration Numbers: ISRCTN26791028, NTR2754., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To explore the incidence of adverse childhood experiences (ACEs) in breast cancer survivors and potential associations with long-term treatment-related sequelae., Sample & Setting: English-speaking breast cancer survivors three or more years from diagnosis with complete treatment response (N = 120) were recruited prior to scheduled survivorship clinic visits., Methods & Variables: Participants in this cross-sectional observational feasibility study rated anxiety, depression, fatigue, sleep disturbance, cognitive issues, resilience, and ACEs (experienced prior to age 18 years). Blood samples were analyzed for inflammatory and epigenetic biomarkers., Results: ACEs assessment was feasible. Higher ACE scores correlated with greater fatigue, anxiety, and depression, and with lower cognitive function (p < 0.05). Resilience was positively associated with cognitive function and negatively associated with fatigue, anxiety, and depression., Implications for Nursing: There is evidence for the impact of ACEs on long-term treatment-related sequelae in women with breast cancer. Oncology nurses should consider incorporating ACEs assessment into the workflow for women receiving survivorship care.

Thyroid hormones (THs) may affect chronic thyrotoxic myopathy (CTM). The relationship between TH sensitivity and CTM is inconsistent. We aimed to investigate the associations between TH sensitivity and the risk of CTM and to screen potential CTMs with strength and function tests. A total of 162 Chinese patients (36.58% men) with Graves' disease were enrolled and divided into CTM and non-CTM groups. TH and sensitivity indices were measured. Muscle power and function were assessed by grip, upper-limb fatigue (ULFT), lower-limb fatigue (LLFT), and squat-up (SUT) tests, and walking pace. Association between sensitivity to TH indices and the risk of developing CTM was assessed via multivariate logistic regression. The diagnostic effectiveness of muscle power and function for predicting CTM was evaluated via receiver operating characteristic (ROC) curves. Thyroid feedback quantile-based index FT 3 (TFQI FT3 ) and the parametric TFQI FT3 (PTFQI FT3 ), TFQI FT4 , and PTFQI FT4 were positively associated with CTM risk by using inverse probability of treatment weighting multivariate logistic regression. For each 1-SD increase in TFQI FT3 and PTFQI FT3 , TFQI FT4 and PTFQI FT4 , the odds ratios for CTM were 1.67 (95% CI = 1.17-2.48) ,1.64 (95% CI = 1.51-2.93), 1.60 (95%CI = 1.12-2.32), 1.58 (95%CI = 1.11-2.30), respectively. LLFT and SUT best predicted male/female CTM, respectively (AUC = 0.89/0.85). In Graves' disease patients, TH sensitivity is associated with CTM development, which can be predicted by SUT and LLFT results., (© 2024. The Author(s).)

Objectives: Persistent skeletal muscle dysfunction in survivors of critical illness due to acute respiratory failure is common, but biological data elucidating underlying mechanisms are limited. The objective of this study was to elucidate the prevalence of skeletal muscle weakness and fatigue in survivors of critical illness due to COVID-19 and determine if cellular changes associate with persistent skeletal muscle dysfunction., Design: A prospective observational study in two phases: 1) survivors of critical COVID-19 participating in physical outcome measures while attending an ICU Recovery Clinic at short-term follow-up and 2) a nested cohort of patients performed comprehensive muscle and physical function assessments with a muscle biopsy; data were compared with non-COVID controls., Setting: ICU Recovery Clinic and clinical laboratory., Patients/subjects: Survivors of critical COVID-19 and non-COVID controls., Interventions: None., Measurements and Main Results: One hundred twenty patients with a median of 56 years old (interquartile range [IQR], 42-65 yr old), 43% female, and 33% individuals of underrepresented race attended follow-up 44 ± 17 days after discharge. Patients had a median Acute Physiology and Chronic Health Evaluation-II score of 24.0 (IQR, 16-29) and 98 patients (82%) required mechanical ventilation with a median duration of 14 days (IQR, 9-21 d). At short-term follow-up significant physical dysfunction was observed with 93% of patients reporting generalized fatigue and performing mean 218 ± 151 meters on 6-minute walk test (45% ± 30% of predicted). Eleven patients from this group agreed to participate in long-term assessment and muscle biopsy occurring a mean 267 ± 98 days after discharge. Muscle tissue from COVID exhibited a greater abundance of M2-like macrophages and satellite cells and lower activity of mitochondrial complex II and complex IV compared with controls., Conclusions: Our findings suggest that aberrant repair and altered mitochondrial activity in skeletal muscle associates with long-term impairments in patients surviving an ICU admission for COVID-19., Competing Interests: Dr. Mayer was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institute of Health K23-AR079583. The work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and National Institute of General Medical Sciences of the National Institute of Health R01AR081002. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: We analysed the COMparison Between All immunoTherapies for Multiple Sclerosis (NCT03193866), a Swedish nationwide observational study in relapsing-remitting multiple sclerosis (RRMS), to identify trajectories of fatigue and their association with physical disability following start of disease-modifying therapy (DMT)., Methods: Using a group-modelling approach, we assessed trajectories of fatigue with the Fatigue Scale for Motor and Cognitive Functions and physical disability with Expanded Disability Status Scale among 1587 and 1818 individuals who initiated a first DMT and had a first DMT switch, respectively, followed during 2011-2022. We investigated predictors of fatigue trajectories using group membership as a multinomial outcome and calculated conditional probabilities linking membership across the trajectories., Results: We identified five trajectories of fatigue in participants who initiated their first DMT: no fatigue (mean starting values=23.7; 18.2% of population), low (35.5; 23.9%), mild (49.0; 21.6%), moderate (61.3; 20.1%) and severe (78.7; 16.1%). While no, low, mild and severe fatigue trajectories remained stable, the moderate trajectory increased to severe fatigue. Similarly, we identified six fatigue trajectories among participants who did a DMT switch, all indicating stable values over time. Women initiating a first DMT were more likely than men to display a severe fatigue trajectory, relative to the no fatigue one. There was a strong association between fatigue and physical disability trajectories., Conclusions: In this cohort of people with actively treated RRMS, self-reported fatigue remained stable or increased over the years following DMT start. There was a strong association between fatigue and disability after DMT start., Competing Interests: Competing interests: KG, YQ and AH are employees at Janssen Pharmaceuticals, Johnson and Johnson. FP has received research grants from Janssen, Merck KGaA and UCB, and fees for serving on DMC in clinical trials with Chugai, Lundbeck and Roche, and preparation of expert witness statement for Novartis., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objective: To assess (i) the impact of self-reported fatigue on functioning in daily life, and (ii) the association with sociodemographics, physical capacity, and work ability among people with post-COVID-19., Design: A cross-sectional study., Subjects: Adults reporting post-COVID-19 symptoms for at least 2 months., Methods: Participants were recruited through social media and responded to an online survey between October 2021 and February 2022 regarding sociodemographics, COVID-19 symptoms, comorbidities, physical and mental fatigue, aerobic capacity, and work ability. Descriptive statistics and logistic regression analyses were used., Results: A total of 614 participants (88% women, mean age 47 years, on average 13 months of symptoms) were included. A majority (≥ 84%) reported both physical fatigue and mental fatigue, according to the Fatigue Severity Scale and Mental Fatigue Scale. The fatigue impacted motivation, physical functioning, work, family, or social life, and increased sensitivity to stress and concentration difficulties. Among the factors, work ability had the strongest association with both physical fatigue and mental fatigue; odds ratio: 0.650 and 0.473, p < 0.001, respectively., Conclusion: This study found that self-reported fatigue is common among people with post-COVID-19, and negatively impacts functioning in daily life. To achieve a sustainable life and work situation, support and targeted rehabilitation interventions may be important.

Lung cancer patients suffer from numerous symptoms that impact their quality of life. This study aims to identify the symptom burden on quality of life in lung cancer patients. This survey used a structured questionnaire to collect data from 8 March 2021 to 12 May 2021. Patient demographic information was collected. The data on symptom burden and quality of life (QOL) of patients were obtained from the QLQ-C30 and the QLQ-LC13. The stepwise multiple regression analysis was used to estimate lung cancer-related symptom burden in relation to quality of life. The study included 159 patients with lung cancer who completed the questionnaire. The mean age of the patients was 63.12 ± 11.4 years, and 64.8% of them were female. The Global Quality of Life score of the QLQ-C30 was 67.87 ± 22.24, and the top five lung cancer-related symptoms were insomnia, dyspnea, and fatigue from the QLQ-C30, and coughing and dyspnea from the QLQ-LC13. The multiple regression analysis showed that appetite loss was the most frequently associated factor for global QOL (β = -0.32; adjusted R 2 : 27%) and cognitive function (β = -0.15; adjusted R 2 : 11%), while fatigue was associated with role function (β = -0.35; adjusted R 2 : 43%), emotional function (β = -0.26; adjusted R 2 : 9%), and social function (β = -0.26; adjusted R 2 : 27%). Dyspnea was associated with physical function (β = -0.45; adjusted R 2 : 42%). Appetite loss, fatigue, and dyspnea were the main reasons causing symptom burdens on quality of life for lung cancer patients. Decreasing these symptoms can improve the quality of life and survival for patients with lung cancer.

Objective: To observe the effect of point-toward-point insertion of elongated needle on post-stroke fatigue and explore its underlying mechanism., Methods: Sixty-four patients with post-stroke fatigue were randomly divided into an observation group (32 cases, 2 cases dropped out) and a control group (32 cases, 2 cases dropped out). In addition to the conventional treatment of western medicine and rehabilitation exercises, Tongdu Tiaoshen (regulating the governor vessel and the spirit) therapy of acupuncture was used in the control group, and acupuncture was applied to Baihui (GV 20), Sishencong (EX-HN 1), Shenting (GV 24), Fengfu (GV 16) and bilateral Fengchi (GB 20) and the needles were retained for 30 min in one treatment. In the observation group, besides the interventions as the control group, point-toward-point insertion of elongated needle was adopted. The needle was inserted from Zhiyang (GV 9) toward Dazhui (GV 14), from Shendao (GV 11) toward Yaoyangguan (GV 3) and from Yaoqi (EX-B 9) toward Yaoyangguan (GV 3); and the needles were retained for 30 min in one treatment. In the two groups, the acupuncture was delivered once daily, 6 times a week, consecutively for 4 weeks. The scores of the fatigue severity scale (FSS), Pittsburgh sleep quality index (PSQI), Hamilton anxiety scale (HAMA), Hamilton depression scale (HAMD), and Fugl-Meyer assessment (FMA) were observed before and after treatment completion in the two groups. Using ELISA, the levels of serum interleukin (IL)-1β, IL-6, IL-10, high-sensitivity C-reactive protein (hs-CRP), and homocysteine (Hcy) were detected before and after treatment completion; and clinical effect was evaluated., Results: The scores of FSS, PSQI, HAMA and HAMD, as well as the levels of serum IL-1β, IL-6, hs-CRP and Hcy were reduced ( P <0.05), and the scores of FMA and the levels of serum IL-10 were increased ( P <0.05) after treatment in comparison with those before treatment in the two groups. Compared with the control group, in the observation group, the scores of FSS, PSQI, HAMA and HAMD, and the levels of serum IL-1β, IL-6, hs-CRP and Hcy were reduced ( P <0.05, P <0.01), and the score of FMA and the level of serum IL-10 were increased ( P <0.05). The total clinical effective rate was 83.3% (25/30) in the observation group, which was higher than 73.3% (22/30) of the control group ( P <0.05)., Conclusion: The point-toward-point insertion of elongated needle alleviates fatigue, anxiety and depression, and ameliorates sleep and motor function in the patients with post-stroke fatigue. It may be related to the attenuation of inflammatory responses.

Purpose: The effects of aerobic exercise interventions for reducing fatigue after cancer treatment are well-established, and the effect of resistance training remains uncertain. Therefore, this systematic review and meta-analysis aim to analyze the effect of resistance training and combined resistance and endurance training on cancer-related fatigue (CRF) in breast cancer patients., Methods: A systematic search for randomized controlled trials (RCTs) was conducted on the PubMed, SPORTDiscus, Embase, and Cochrane databases, focusing on the effect of supervised resistance training and combined supervised resistance and endurance training on CRF. Random-effect models were employed for calculating the standardized mean difference (SMD). Risk of bias was assessed with risk of bias 2 (RoB2), and certainty of evidence was judged according to the GRADE approach., Results: A total of 9 RCTs with 1512 participants were included, and data from 866 participants in 8 RCTs were used for the meta-analysis. The risk of bias was deemed low in seven studies, while one study exhibited attrition bias, and one showed possible selection bias. Resistance training probably reduce the total fatigue (SMD= -0.30, 95% CI -0.52, -0.08, p=0.008), with individual studies showing small effects on physical and emotional CRF. A combined resistance and endurance training reduce total fatigue (SMD= -0.34, 95% CI -0.51, -0.17, p= 0.0001), with individual studies indicating moderate effects on physical fatigue, in daily life fatigue, and small effects on emotional and cognitive CRF., Conclusion: Both supervised resistance training and combined resistance and endurance training have a small effect on total CRF. There is a trend towards an influence of intensity, with higher intensity potentially resulting in lower total CRF., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: In adults with serious respiratory illness, fatigue is prevalent and under-recognised, with few treatment options. The aim of this review was to assess the impact of graded exercise therapy (GET) on fatigue in adults with serious respiratory illness., Methods: Electronic databases were searched to identify randomised controlled trials (RCTs) testing GET (involving incremental increases in exercise from an established baseline) in adults with serious respiratory illness. The primary outcome was fatigue and secondary outcomes were health-related quality of life (HRQoL) and adverse events. Two authors independently screened for inclusion, evaluated risk of bias and extracted data., Results: 76 RCTs were included with 3309 participants, most with a diagnosis of COPD or asthma. Reductions in fatigue measured by the Chronic Respiratory Disease Questionnaire fatigue domain score were demonstrated following GET consisting of aerobic with/without resistance training (mean difference (MD) 0.53 points, 95% CI 0.41-0.65, 11 RCTs, 624 participants) and GET using resistance training alone (MD 0.58 points, 95% CI 0.21-0.96, two RCTs, 82 participants) compared with usual care. Although the mean effect exceeded the minimal important difference, the lower end of the confidence intervals did not always exceed this threshold so the clinical significance could not be confirmed. GET consistently improved HRQoL in people with a range of chronic respiratory diseases on multiple HRQoL measures. No serious adverse events related to GET were reported., Conclusion: GET may improve fatigue alongside consistent improvements in HRQoL in people with serious respiratory illness. These findings support the use of GET in the care of people with serious respiratory illness., Competing Interests: Conflicts of interest: L. Romero declares funding from the European Respiratory Society to design search strategies for this review. A.E. Holland declares authorship on four of the systematic reviews included in this study. A.E. Holland declares no other conflicts of interest. All other authors have nothing to disclose., (Copyright ©The authors 2024.)

Objective: This study was conducted to determine the effect of relaxation exercise on fatigue symptoms in hemodialysis patients., Methods: This is a meta-analysis study. The literature review was carried out by searching studies published between 2011 and 2020. This meta-analysis was recorded on PROSPERO in the National Health Research Institute (Registration no: CRD42022313646)., Results: Seven studies meeting the inclusion criteria were included in the meta-analysis. The effect size of the studies included in the meta-analysis was found to be g=1.232 (p=0.028), which indicated a "huge effect size." The scale used in the subgroup analyses, the application time of the relaxation exercise, and the number of relaxation exercise applications were evaluated, and a significant difference was found at p<0.05., Conclusion: Relaxation exercises can be used as an effective method for reducing fatigue in hemodialysis patients.

Almost half of ischemic stroke (IS) survivors have poststroke fatigue (PSF) during rehabilitation, which can reduce their rehabilitation compliance and quality of life. The primary link of PSF management is early identification, which can guide bundle of care for prevention. This study aimed to explore the predictive value of serological indicators for guiding bundle of care to prevent the occurrence of PSF among IS survivors. This study was a prospective observational study. A total of 350 patients with IS who were hospitalized in 2 tertiary hospitals in Nanning from October 2022 to September 2023 were selected. The general data of patients and serological indicators within 24 hours of admission were collected. Based on the follow-up results, the patients were divided into the PSF group and the NPSF group. Multivariate logistic regression analysis was used to screen the risk factors affecting the occurrence of PSF, and the receiver operating characteristic curve (ROC curve) method was used to analyze the predictive value of this factor. The incidence of acute-phase PSF among elderly patients with IS was 49.26%. The elevated levels of fasting plasma glucose (FPG) (OR = 1.485, 95% CI: 1.145-1.925, P = .003), total cholesterol (TC) (OR = 1.394, 95% CI: 1.013-1.917, P = .041), C-reactive protein (CRP) (OR = 1.394, 95% CI: 1.013-1.917, P = .041), and homocysteine (Hcy) (OR = 1.370, 95% CI: 1.233-1.524, P < .001) were risk factors of PSF in elderly patients with acute IS (P < .05). FPG (area under the curve = 0.632), TC (area under the curve = 0.621), CRP (area under the curve = 0.889), and Hcy (area under the curve = 0.807) had a good predictive value for acute-phase PSF, and the combination of the 4 indicators could further improve the predictive efficacy (area under the curve = 0.938, sensitivity 86.2%, specificity 90.7%, P < .05). The elevated levels of FPG, TC, CRP, and Hcy could predict the risk of PSF, and the combination of the 4 indicators can effectively improve prediction efficiency and provide a reference for guiding the formulation of bundle nursing programs., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Advanced cancer patients commonly suffer from a fatigue-sleep disturbance symptom cluster. Baduanjin is considered a promising mind-body exercise for relieving the fatigue-sleep disturbance symptom cluster. However, few studies have investigated a tailored Baduanjin for advanced cancer patients. The proposed study will create an optimized Baduanjin exercise program to adapt to advanced cancer patients and evaluate the effect of a Simple Sitting Baduanjin (SSBDJ) mind-body exercise on the fatigue-sleep disturbance symptom cluster among advanced cancer patients., Methods: The study will be a prospective, assessor-blinded, two-arm, randomized controlled trial, involving a 12-week intervention and 4-week follow-up. A total of 108 advanced cancer patients experiencing the fatigue-sleep disturbance symptom cluster will be recruited from two tertiary general hospitals in China. Participants will be randomized to an experimental group (n = 54) or a control group (n = 54). The experimental group will receive a 12-week SSBDJ intervention plus the usual care, and the control group will receive only the usual care. Outcomes including fatigue-sleep disturbance symptom cluster, fatigue, sleep disturbance, and quality of life will be measured before the intervention, at the 4th, 8th, and 12th weeks of the intervention, and 4 weeks after the intervention. The intention-to-treat principle and a generalized estimating equation will be used to analyze data., Discussion: This study may produce a new Baduanjin exercise prescription that is user-friendly, simple to execute, more targeted, and adaptable. If proven effective, this approach may be integrated into routine cancer care to manage the fatigue-sleep disturbance symptom cluster and improve QOL in advanced cancer patients., Trial Registration: Chinese Clinical Trial Registry, ChiCTR-2,300,072,331. Registered on 9 June 2023., (© 2024. The Author(s).)

Background: Fatigue is a commonly reported clinical symptom, yet research on fatigue in children with severe asthma is missing. We aimed to explore the extent of fatigue in severe pediatric asthma and identify associated factors., Method: This study was conducted within the Pediatric Asthma Non-Invasive Diagnostic Approaches (PANDA), an observational cohort of 6- to 17-year-old Dutch children with severe asthma. The Pediatric Quality of Life Inventory Multidimensional Fatigue Scale (PedsQL™-MFS) was used to measure self-reported fatigue. Fatigue levels were compared with a general pediatric Dutch population using linear regression, and quantifying the prevalence of "fatigued" (-2 < Standard deviations [SD] ≤ -1) and "severely fatigued" (SD ≤ -2) children. Secondly, we performed linear regression analyses to explore whether fatigue levels were independently associated with asthma attacks, comorbidities, medication, pulmonary function, symptom control, and asthma-related quality of life (QoL)., Results: Severe pediatric asthma patients (n = 78, mean age 11.8 ± 3.1 years) reported significantly more fatigue than Dutch peers (n = 328, mean age 11.8 ± 3.2 years) mean difference in z-score: -0.68; 95%CI -0.96, -0.40. In the severe asthma group, 28.2% scored as "fatigued" and 15.4% as "severely fatigued," compared with 14.0% and 3.4% in the general population. In pediatric asthma patients, asthma-related QoL (β = 0.77, p < .01, ΔR 2  = .43), symptom control (β = 0.56, p < .01, ΔR 2  = .24) and a dysfunctional breathing pattern (β = -0.36, p < .01, ΔR 2  = .12) were most strongly associated with fatigue scores., Conclusion: Fatigue is a common symptom in children with severe asthma and is associated with multiple clinical factors and patient-reported outcomes. It should be considered as an important treatment target., (© 2024 The Author(s). Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Objective: Current studies have indicated that diabetes mellitus (DM) is highly prevalent in patients with cancer, but there is little research on consequences on the well-being of patients during cancer treatment. This analysis evaluates the relationship between DM and patient-reported outcomes (PRO) in patients with cancer, using a large and well-characterized cohort., Methods: This study utilized the Total Cancer Care protocol at the University of Utah Huntsman Cancer Institute. For this analysis, we integrated data from electronic health records, the Huntsman Cancer Registry, and routinely collected PRO questionnaires. We assessed the association between DM in patients with cancer and PRO scores for anxiety, depression, fatigue, pain interference, and physical function using multiple linear regression and t-tests., Results: The final cohort comprised 3512 patients with cancer, with a mean age of 57.8 years at cancer diagnosis. Of all patients, 49.1% (n = 1724) were female, with 82.0% (n = 2879) patients reporting PROs at least at one time point. Compared with patients who responded, nonresponders were more often female (p = 0.0035), less frequently non-Hispanic White (p = 0.0058), and had a higher BMI (p = 0.0759). Patients with cancer and diabetes had worse PRO scores for anxiety (p = 0.0003), depression (p < 0.0001), fatigue (p < 0.0001), pain interference (p < 0.0001), and physical function (p < 0.0001) compared to patients with cancer without diabetes. Significant associations between diabetes and PRO scores were observed for anxiety (β ± SE: 1.27 ± 0.48; p = 0.0076), depression (β ± SE: 1.46 ± 0.45; p = 0.0011), fatigue (β ± SE: 2.11 ± 0.52; p < 0.0001), pain interference (β ± SE: 1.42 ± 0.50; p = 0.0046), and physical function (β ± SE: -2.74 ± 0.48; p < 0.0001)., Conclusions: The results of this study suggest that patients with cancer and diabetes may be at greater risk for anxiety, depression, fatigue, higher pain interference, and reduced physical function. Strengthening diabetes management is imperative to address the negative impact of diabetes on PROs. In particular, this may be true for patients with skin, breast, prostate, and kidney cancer., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)