Self-reported Fatigue Research Articles

Self-Reported Fatigue by the Chalder Fatigue Questionnaire and Mortality in Brazilian Hemodialysis Patients: The PROHEMO

Background: The existing data support the Chalder Fatigue Questionnaire (CFQ-11) as a valid instrument to assess fatigue in maintenance hemodialysis (MHD) patients. The objective of this work was to investigate whether self-reported fatigue can serve as an independent prognostic indicator for mortality in MHD patients. Methods: The data are from 233 adult patients enrolled in the cohort “The Prospective Study of the Prognosis of Chronic Hemodialysis Patients” (PROHEMO) developed in Salvador, BA, Brazil. The Brazilian version of the validated CFQ-11 was used to calculate self-reported fatigue. The CFQ-11 scores may range from 0 to 33; higher scores represent more fatigue. Fatigue categories were created based on proposed cut point: absence or mild degree if CFQ-11 scores <4 and moderate to severe if scores ≥4. Cox models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of associations between fatigue and mortality with adjustments for sociodemographic factors, time on dialysis, education, economic class, hemoglobin concentration, diabetes, heart failure, depression, and other psychiatric disorders. Results: The mean age was 51.5 ± 2.5 years, 58% were male, and 30% were diabetic. Self-reported moderate to severe fatigue was reported by 71% of patients. The mortality rate was 8.6 cases/100 person-years. Patients with moderate to severe fatigue had a more than threefold mortality rate (HR = 3.07, 95% CI: 1.19, 7.93) compared to patients with absent or mild fatigue, after extensive adjustments for covariates. Conclusion: The study provides evidence that self-reported fatigue can help identify MHD patients at higher risk of earlier death.

Efficacy of Sutimlimab in Improving FACIT-Fatigue Scores in Patients with Cold Agglutinin Disease: A Post-Hoc Analysis of the Phase 3 Cadenza (Part A) Study

Background Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia characterized by chronic hemolysis mediated by classical complement pathway activation. Chronic inflammation and anemia associated with CAD can lead to profound fatigue and general weakness, impacting the patients' quality of life. Sutimlimab is a first-in-class humanized monoclonal antibody approved for the treatment of CAD. To assess the effect of sutimlimab on patients' self-reported fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-Fatigue] scores) in CAD, a post-hoc analysis of the CADENZA Part A study was carried out. Objective To assess the effect of sutimlimab vs placebo on FACIT-Fatigue total score, and individual items of the FACIT-fatigue scale in patients with CAD. Methods CADENZA (NCT03347422) Part A was a phase 3, double-blind, 26-Week study where patients were randomized (1:1) to receive intravenous sutimlimab or placebo. The 13-item FACIT-Fatigue questionnaire comprising 11 fatigue items and 2 energy items (‘I have energy’ or 'I am able to do my usual activities') was scored on a 0 (“not at all”) to 4 (“very much”) response scale, and the total scores ranged from 0 to 52; higher scores indicated less fatigue. Least square (LS) mean difference (sutimlimab vs placebo) in change from the baseline (BL) in FACIT-Fatigue total score were estimated at all visits using mixed model for repeated measures. Treatment assessment timepoint (TAT) was the average of values from Week 23, 25, and 26 visits. Patients were considered responders if they achieved a change from BL in FACIT-Fatigue total score of ≥5, did not receive blood transfusions from Week 5 through TAT, and did not take any protocol prohibited CAD medications. Patients with missing data at a given visit were considered non-responders. Time to first response to treatment was assessed using the Kaplan-Meier product limit method. For the item level analysis of the FACIT-Fatigue scale, the proportion of patients reporting the two worst response options 'Quite a bit' or ‘Very much’ for fatigue items and ‘Not at all’ or ‘A little bit’ for energy items was calculated at BL and Week 26. Results A total of 42 patients were included in the study (sutimlimab group: n=22; placebo group: n=20). The median (range) age of patients was 66.0 (46-88) years and 78.6% (n=33) were female. The mean (SD) FACIT-Fatigue total score for the pooled population at BL was 32.30 (11.83). About 79% of patients (n=33) had a total score below the general healthy population mean of 43. The LS mean (95% CI) difference (sutimlimab vs placebo) in change from BL in the FACIT-Fatigue total score was 4.97 (0.35─9.60) at Week 1 and 8.93 (4.00─13.85) at TAT. The nominal significant difference that started at Week 1 (rapid treatment effect) was sustained throughout Part A ( Figure 1). Overall, the fatigue response rate was higher in the sutimlimab group than placebo group throughout the study. The median time (95% CI) to first FACIT-Fatigue response in the sutimlimab and placebo groups were 3.1 (1.1─3.1) and 9.1 (3.3─22.4) weeks (log-rank test p&amp;lt;0.05), respectively. At BL, ~25-30% of the patients had reported the two worst response options (‘Quite a bit’ or 'Very much') for most of the FACIT-fatigue items. Around 40.5% (17/42) of the patients responded with one of the two worst options for item 'I feel tired', and more than half of the patients (22/42; 52.4%) reported one of the two worst options (‘Not at all’ or 'A little bit') for item 'I have energy'. At Week 26, lower proportion of patients in sutimlimab group reported one of the two worst options for fatigue and energy items compared with the placebo group ( Figure 2). Conclusion Sutimlimab treatment led to rapid and sustainable improvement in FACIT-Fatigue scores and higher response rates as compared to placebo. Number needed to treat to observe a sutimlimab-related FACIT-Fatigue benefit was 4. The proportion of severe FACIT-Fatigue answers for fatigue and energy items was noticeably lower in sutimlimab-treated patients at Week 26 compared to placebo, highlighting the effect of sutimlimab in improving almost all dimensions of FACIT-Fatigue scale.

A Real-World Evidence Review of Post-Marketing Safety and Compliance with Pegcetacoplan in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) in the US

Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hematologic condition characterized by complement-mediated, life-threatening hemolysis and thrombosis which are associated with significant impacts on health-related quality of life (HRQoL). Pegcetacoplan is the first targeted complement component 3 (C3) therapy approved for adults with PNH (US) and adults with PNH plus anemia despite receiving a complement component 5 inhibitor (C5i) for ≥3 months (EU). In clinical trials including patients with PNH who were C5i-experienced or -naive, pegcetacoplan significantly improved levels of hemoglobin (Hb) and lactate dehydrogenase (LDH) and reduced transfusion burden. Pegcetacoplan had a favorable safety profile in parent studies and an ongoing long-term, rollover, open-label extension study (NCT03531255). Compliance with pegcetacoplan treatment was high across all clinical studies. In the US real-world OPERA and Adelphi PNH Disease Specific Programme™ (DSP) patient-reported outcomes (PRO) studies, improvements in levels of Hb and LDH, along with self-reported fatigue and cognitive outcomes, were observed. Pegcetacoplan treatment also led to reductions in the frequency and severity of PNH symptoms (including shortness of breath and fatigue) and improvements in social, physical, and emotional HRQoL domains in the US real-world Voice of the Patient PRO study. Further, both patient and physician satisfaction with pegcetacoplan treatment was high in the Adelphi PNH DSP study. However, to date, compliance and safety with pegcetacoplan treatment in the real-world setting have not been described. The objective of this real-world evidence review study was to evaluate compliance and safety with pegcetacoplan treatment in patients with PNH in the US post-marketing setting. Methods: Post-marketing data from the US, including the number of patients who received pegcetacoplan and reported safety events, were collected and analyzed from the pegcetacoplan Risk Evaluation and Mitigation Strategies (REMS) program which controls the distribution of pegcetacoplan and the pharmacovigilance safety database through May 13, 2023. Treatment compliance was calculated as the proportion of days a patient had the drug in possession, divided by the total number of days of follow-up, using central pharmacy prescription refill data. Thrombosis (a leading cause of death in patients with PNH prior to the availability of complement inhibitors) and meningococcal infections (a potential risk with complement inhibitors) were safety events of interest. To reduce the risk of serious meningococcal infections, clinical trial protocols and pegcetacoplan labeling required vaccination against Streptococcus pneumoniae; N meningitidis types A, C, W, Y, and B; and Haemophilus influenzae type B before starting treatment with pegcetacoplan. If pegcetacoplan treatment must be initiated before vaccination, the US label mandates prophylactic antibiotic use. In this study, the rates of thrombosis and meningococcal infection per 100 patient-years were estimated based on the total number of thrombosis and meningococcal infection events reported in the REMS program. Results: As of May 13, 2023, the cumulative pegcetacoplan exposure was 273.10 patient-years in the US post-marketing setting. Based on prescription refill data, compliance with pegcetacoplan treatment was ~98%. There were 2 confirmed thrombotic events reported and the incidence of thrombotic events was 0.73 events/100 patient-years in 273.10 patient-years. Similar to clinical trials, no meningococcal infections were reported in the US post-marketing setting. Conclusions: The high compliance rate and favorable safety profile of pegcetacoplan in the US post-marketing setting were consistent with clinical trial observations. These data, coupled with the effectiveness on hematologic parameters and improvements in symptoms and HRQoL reported in pegcetacoplan real-world PRO studies, support a positive benefit:risk profile for pegcetacoplan in the real-world setting.

Associations Between Self-Reported Sleep Quality, Fatigue Severity, Factors Associated With Successful Cessation, and Cessation Beliefs Among Regular Smokers.

Smokers report poorer sleep than nonsmokers and sleep quality deteriorates further during cessation, increasing risk of smoking relapse. Better understanding of the relationship between sleep and relapse-related outcomes could inform novel approaches to smoking cessation support. The aim of this study was to investigate same-day associations of self-reported sleep quality and fatigue severity with factors associated with successful cessation and cessation beliefs, among regular smokers. This cross-sectional observational study (n = 412) collected self-reported sleep quality, fatigue severity, and factors associated with successful cessation and cessation beliefs among regular smokers via an online survey (60% male). There was evidence of an association between sleep quality (SQ) and reduced 24-hour (β = -0.12, p = .05) and lifetime (β = -0.09, p = .04) abstinence self-efficacy. In addition, poorer SQ and higher fatigue severity (FS) were associated with increased smoking urges (SQ: β = 0.27, p < .001; FS: β = 0.32, p < .001), increased barriers to cessation (SQ: β = 0.19, p < .001; FS: β = 0.32, p < .001), and increased perceived risks to cessation (SQ: β = 0.18, p < .001; FS: β = 0.26, p < .001). Fatigue severity was weakly associated with increased perceived benefits to cessation (β = 0.12, p = .017). Self-reported sleep quality and fatigue severity were associated with multiple factors associated with successful cessation and cessation beliefs. Further research is needed to extend these findings by using different methods to identify the temporal direction of associations and causality. This study is the first to examine associations between sleep quality, fatigue severity, and factors associated with successful cessation and cessation beliefs. Findings show that both sleep quality and fatigue severity are associated with multiple factors associated with successful cessation and could be modifiable targets for future smoking cessation interventions. Furthermore, our data suggest that fatigue severity has an independent effect on multiple factors associated with successful cessation when accounting for sleep quality. This indicates that fatigue, independent of sleep quality, could be an important factor in a quit attempt.

QOL-05. EXPLORATORY ANALYSIS OF COGNITIVE BEHAVIORAL THERAPY FOR INSOMNIA (CBT-I) AMONG PATIENTS WITH PRIMARY BRAIN TUMOR: EFFECTS ON DEPRESSION, ANXIETY, AND LIFE QUALITY

Abstract BACKGROUND Sleep disturbance is among the most common complaints endorsed by patients with a brain tumor diagnosis, yet the delivery of behavioral insomnia treatment is not standard practice in neuro-oncology. Our pilot trial of a 6-session group-based telehealth CBT-I program among primary brain tumor patients demonstrated clinically significant improvements in self-reported insomnia, fatigue, and sleep quality. In other cancer patient samples, CBT-I is also associated with improvements in psychosocial outcomes beyond sleep; thus, the aim of this exploratory analysis was to examine change in depression, anxiety, and life quality among primary brain tumor patients enrolled in CBT-I. METHODS This was a single-arm ORBIT Model Phase IIa proof-of-concept trial. N = 40 cognitively-intact participants (Mage = 52.4 + 12 years; 50.0% female) with a primary brain tumor and insomnia enrolled in a 6-week group-based telehealth CBT-I intervention with weekly 90-minute sessions led by graduate students in clinical psychology. Questionnaires (PHQ-9, GAD-7, EORTC-QLQ-30) were completed at baseline and 6 weeks. Within-person clinically significant improvement was calculated for intervention completers (n = 34) based on established cutoffs. RESULTS Approximately one-third of participants experienced clinically significant improvements in symptoms of depression (n = 12, 35.3%) and generalized anxiety (n = 11, 32.3%) following CBT-I, with 0 participants experiencing a clinically significant worsening of symptoms. Thirty-two of thirty-four participants (94.1%) reported clinically significant improvement in at least 1 domain of life quality spanning physical, role, emotional, and/or social functioning. CONCLUSIONS Findings suggest that a brief behavioral intervention for insomnia, CBT-I, may improve depression, anxiety, and life quality in addition to sleep among primary brain tumor patients. RESULTS from this proof-of-concept trial suggest proceeding to a test of CBT-I in comparison to a control group in order to bolster internal validity. In addition, future studies will examine sleep and related psychosocial outcomes over a longer follow-up period to assess maintenance of intervention effects.

The FRAGILE clinical trial: the impact of the coronary artery bypass graft in frailty

Abstract Background The exponential increase in the elderly population has been observed worldwide, and it implies a higher incidence of coronary artery disease and, consequently the need for coronary artery bypass graft (CABG). The growing number of elderlies is also related to frailty, a syndrome that affects at least 10% of the elderly population and is an exceedingly effective parameter for correlating with the adverse effects of aging. The impact of frailty concerning mortality and morbidity is well established however, there are no studies regarding the outcomes of CABG and its techniques in frail patients. Purpose To evaluate the impact of coronary artery bypass graft surgery in patient's frailty and compare the differences in the frailty index after a 6-month follow-up between the groups off-pump and on-pump. Methods This was a subanalysis of the FRAGILE trial, a brazilian multicenter, randomized, controlled clinical trial that analyzed 169 patients aged 60 years or older undergoing coronary artery bypass graft surgery with (on-pump) and without (off-pump) cardiopulmonary bypass. Using the Fried's Frailty Criteria, we classifed the patients into frail, pre-frail, and non-frail and also evaluated the five paramenters of this criteria. The patients were divided into two groups: the off-pump CABG group (n=87) and the on-pump CABG group (n=82), and compared unintentional weight loss, self-reported fatigue, physical activity level, grip strength, and gait speed before and after surgery, and between groups. The study was approved by the local Ethics Committee and all patients signed the informed consent. Results We observed an improvement in the frailty of patients undergoing CABG. Overall, over 50% of frail patients became pre-frail after CABG, and only 3% of the total patients were classified as frail after 6 months of surgery (Fig 1A). No patient was classified as non-frail preoperatively in both groups because it was one of the exclusion criteria. There is no difference between the groups off-pump and on-pump (Fig 1B). The total time of physical activity, the gait speed, and the self-reported fatigue were positively impacted regardless of surgical technique. However, grip strength and unintentional weight loss were improved only in the group that underwent off-pump CABG surgery. Patients reported practicing an average more time of exercises, improved gait speed, and claimed to be less fatigated compared to the before-surgery measurements. However, grip strength and unintentional weight loss were improved only in the group that underwent off-pump CABG surgery (Table 1). Conclusion CABG positively impacts patients' frailty after six months of surgery. Both techniques, on-pump and off-pump, showed positive results when comparing frailty features before and after CABG surgery. Nevertheless, the off-pump CABG was the only technique that played a role in improving grip strength and unintentional weight loss of patients after 6 months of surgery.Frailty classificationFrailty's parameters

Reducing Vocal Fatigue With Bone Conduction Devices: Comparing Forbrain and Sidetone Amplification.

Altered auditory feedback research aims to identify methods to strengthen speakers' awareness of their own voicing behaviors, diminish their perception of vocal fatigue, and improve their voice production. This study aims to compare the effects of two bone conduction devices that provide altered auditory feedback. Twenty participants (19-33 years old, age: M [SD] = 25.5 [3.85] years) participated in a vocal loading task using a standard Forbrain device that provides filtered auditory feedback via bone conduction and a modified Forbrain device that provides only sidetone amplification, and a control condition with no device was also included. They rated their vocal fatigue on a visual analog scale every 2 min during the vocal loading task. Additionally, pre- and postloading voice samples were analyzed for acoustic voice parameters. Across all participants, the use of bone conduction-altered auditory feedback devices resulted in a lower vocal fatigue when compared to the condition with no feedback. During the pre- and postvoice samples, the sound pressure level decreased significantly during feedback conditions. During feedback conditions, spectral mean and standard deviation significantly decreased, and spectral skew significantly increased. The results promote bone conduction as a possible preventative tool that may reduce self-reported vocal fatigue and compensatory voice production for healthy individuals without voice disorders.

Abstract 18530: Associations Among Self-Reported and Physiologic Sleep Measurements and Fatigue in Adults Following Major Cardiac Events

Background: Insufficient sleep contributes to fatigue and cardiometabolic disorders. Current sleep measures vary in accuracy, with weak correlations between self-report and physiologic measures. Developing reliably associated self-report and physiologic sleep measures can optimize data collection methods. Purpose: Investigate correlations between self-reported and physiologic sleep measures in cardiac rehabilitation patients and determine associations with fatigue. Methods: Participants (N = 25, 58% male, 89% non-Hispanic white, mean age = 61 years) recruited from cardiac rehabilitation centers participated in a three-arm RCT. Inclusion criteria were experiencing a myocardial infarction or revascularization procedure, enrollment in cardiac rehabilitation, and experiencing depression or anxiety. Participants without complete sleep measures were excluded. Data was collected at baseline, 3-, and 6-months. Sleep was measured over 8 days with an investigator-developed self-report diary and an ActiGraph GT9X Link accelerometer. ActiGraphs collected data with a 30Hz sampling rate and were scored using the autodetected sleep periods to determine total sleep time. Mean daily minutes of sleep were calculated from self-report and ActiGraph data. Participants also completed a demographics survey and Fatigue Severity Scale. Statistical methods included Pearson correlation coefficients with 95% confidence intervals (CI) estimated with Fisher's r-to-z transformation. Results: Results showed self-reported and ActiGraph measured sleep were highly correlated (r = 0.889, [95% CI 0.812, 0.935], p &lt; 0.001). Fatigue was not correlated with self-reported (r = 0.074, [95% CI -0.206, 0.342] p = 0.607) or ActiGraph measured sleep (r = 0.150, [95% CI -0.131, 0.408] p = 0.295). Even though the finding was non-significant, the correlation between fatigue and ActiGraph measured sleep was larger than self-reported sleep. Conclusion: Accurate sleep measures are essential to inform future research and interventions. Unlike past work, this investigator-developed, self-report measure was strongly correlated with the physiologic measure. Researchers should consider reliability when selecting sleep measures.

Fatigue risk assessment of a Helicopter Emergency Medical Service crew working a 24/7 shift pattern: results of a prospective service evaluation

BackgroundThe work of Helicopter Emergency Medical Services (HEMS) teams crosses the boundaries of several high-risk occupations including medicine, aviation, and transport. Working conditions can be challenging and operational demands requires a 24-h rota, resulting in disruption of the normal circadian rhythm. HEMS crews are therefore prone to both mental and physical fatigue. As fatigue in medical providers is linked to poor cognitive performance, degradation of psychomotor skills and error, this study aimed to explore the existence of predictable patterns of crew-fatigue in a HEMS service.MethodsHEMS medical crew members working a 3-on 3-off forward rotating rota with a 5-week shift cycle were asked to do psychomotor vigilance tests (PVT) as an objective measure of fatigue. PVT testing was undertaken at the start, mid- and at the end of every shift during a full 5-week shift cycle. In addition, they were asked to score subjective tiredness with the Samn-Perelli Fatigue Scale (SPFS), and to keep a Transport Fatigue Assessment shift log, wherein they noted shift characteristics potentially related to fatigue. Primary outcome of interest was defined as the change in PVT and SPFS scores over time.ResultsMean baseline resting PVT in milliseconds at the start of the study period was 427 [390–464]. There was an overall trend towards higher PVT-scores with shift progression mean [95% CI] PVT at the start of shifts 447 [433–460]; halfway through the shift 452 [440–463]; end of the shift 459 [444–475], p = 0.10), whereas SPFS scores remained constant. Within a 5 week forward-rotating cycle, an overall trend towards a gradual increase in both average PVT (from 436 [238–454] to 460 [371–527, p = 0.68] ms;) and SPFS (from 2.9 [2.6–3.2] to 3.6 [3.1–4.0], p = 0.38) was observed, although significant interindividual variation was present. Reported SPFS scores ≥ 4 (moderate fatigue) were mainly related to workload (number of jobs) and transport mode (car-based shifts).ConclusionAn overall trend towards a decline in psychomotor vigilance and an increase in self-reported tiredness was found for HEMS crew over a 5-week shift cycle. Using a bespoke predictive fatigue tool on a day-to-day basis could increase fatigue awareness and provide a framework to which relevant mitigating options can be applied.

Patient-Reported Outcomes (PROs) in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) Treated with Crovalimab and Eculizumab: Results from the Phase III Randomized COMMODORE 2 and COMMODORE 1 Trials

Introduction COMMODORE 2 (NCT04434092) and COMMODORE 1 (NCT04432584) are global, randomized, open-label, multicenter Phase III trials evaluating crovalimab (crova) vs eculizumab (ecu) in patients (pts) with PNH. COMMODORE 2 tested the non-inferiority of crova vs ecu in C5i-naive pts and demonstrated that crova was non-inferior to ecu for hemolysis control, transfusion avoidance, breakthrough hemolysis, and hemoglobin stabilization (Röth EHA 2023; #S181). In both studies, crova was well tolerated for both C5i-naive and C5i-experienced pts (Röth EHA 2023; #S181, Scheinberg EHA 2023; #S183). To investigate the efficacy of crova vs ecu from a pt perspective, PRO tools were used to assess fatigue, PNH-related symptoms, functioning, and global health status/quality of life (GHS/QoL) among COMMODORE 2 and COMMODORE 1 pts. Methods In COMMODORE 2, C5i-naive pts were randomized 2:1 to receive crova or ecu during a 24-week primary treatment period. In COMMODORE 1, C5i-experienced pts receiving ecu at study start were randomized 1:1 to receive crova or ecu during a 24-week primary treatment period. Pts received crova as a weight-based tiered regimen (Liu ASH 2022; #293) that included loading doses followed by maintenance doses via subcutaneous injection every 4 weeks, or ecu via intravenous infusion every 2 weeks (900 mg per label). After completing 24 weeks of treatment, COMMODORE 1 and 2 pts randomized to crova continued crova, and those randomized to ecu switched to crova if continuing in the extension period. Paper PRO questionnaires were completed by adult pts at baseline (BL) and at Weeks 2, 5, 9, 17, and 25 during the primary treatment period (up to Week 25) and during the crova extension period (from Week 25 onwards). Fatigue was assessed with the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale (higher scores indicate lower fatigue severity). Additional PNH symptoms (dyspnea, dysphagia, headaches, abdominal pain, chest pain, and erectile dysfunction) were assessed using relevant questions selected from the European Organisation for Research and Treatment of Cancer (EORTC) Item Library (EORTC IL-40; higher scores indicate worse symptoms). Physical function, role function, and GHS/QoL were assessed with the EORTC Quality of Life Questionnaire Core 30 (EORTC QLQ-C30; higher scores indicate better functioning/quality of life). Results For the primary analysis, COMMODORE 1 randomized 45 pts to crova and 44 to ecu, and enrolled 38 pts in the descriptive arm; COMMODORE 2 randomized 135 pts to crova and 69 to ecu. In COMMODORE 2, C5i-naive pts in both arms showed rapid and sustained improvement across all PRO measures during the primary treatment period. Clinically meaningful improvement (≥5 points; Cella ASH 2021; #1952) in mean FACIT-Fatigue scores from BL occurred in both arms, with numerically higher improvement with crova (crova: 7.8, 95% CI: 6.5, 9.1; ecu: 5.2, 95% CI: 3.4, 6.9; Table 1). Mean fatigue levels of pts treated with crova improved by Week 2 and were similar to normative population values by Week 25. Analysis of the individual FACIT-Fatigue items was also conducted. Additionally, improvements were observed for both treatment arms in all EORTC IL-40 symptoms and in the functioning and GHS/QoL scales of the EORTC QLQ-C30, with numerically greater improvement with crova for most scales (Table 2). The improvements with crova treatment were maintained during the crova extension period. In COMMODORE 1, C5i-experienced pts randomized to receive crova or ecu maintained BL levels of fatigue, PNH symptoms, functioning, and GHS/QoL scores throughout the primary treatment period (Tables 1 and 2) and with crova treatment during the extension period. There was no meaningful change in the mean values of any PRO scores after pts switched from ecu to crova at Week 25. Conclusions C5i-naive pts inCOMMODORE 2 experienced rapid and sustained improvements from BL in fatigue, PNH symptoms, functioning, and GHS/QoL scores while on treatment with crova and ecu, with numerically greater improvement in fatigue and most GHS/QoL scales in the crova arm. C5i-experienced pts in COMMODORE 1 maintained BL levels during the first 24 weeks of treatment with crova or ecu. These trends were maintained after pts were switched from ecu to crova. These data provide supportive evidence for the treatment benefit of crovalimab for self-reported fatigue and quality of life.

Health-Related Quality of Life and Symptom-Specific Functional Impairment Among Patients Treated with Parenterally Administered Complement Inhibitors for Paroxysmal Nocturnal Hemoglobinuria

Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, life-threatening, stem cell disorder that renders red blood cells vulnerable to complement-mediated hemolysis. This study describes the health-related quality of life (HRQoL) and symptom-specific functional impairment of patients with PNH in a real-world setting. Methods: US-based adults with PNH treated with a parenterally administered complement inhibitor (PACI) for ≥6 months completed an online, cross-sectional, observational survey; a subset of patients also participated in individual semi-structured qualitative interviews after completing the survey. The survey included the PROMIS® 29+2 Profile v2.1 (PROMIS 29+2) to measure HRQoL. The FACIT Fatigue, Neuro-QOL Item Bank v2.0 Cognitive Function Short Form, and PROMIS Item Bank v1.0 Dyspnea Functional Limitations 10a Short Form measured functional impairment associated with specific symptoms of PNH. For each patient with PNH who completed the online survey, up to 3 age- (+/- 3 years) and sex-matched adults without PNH also completed the survey. The HRQoL and functional impairment of the PNH sample was compared to that of general population (GP) sample using independent samples t-tests or Mann-Whitney tests. To further explore the experiences of patients with PNH, the association between HRQoL/functional impairment and fatigue severity was investigated. Patients with PNH were grouped according to their self-reported fatigue severity over the past 7 days (very mild or mild vs moderate, severe, or very severe [no patients reported no fatigue]). Differences in scores across these 2 groups were tested. Data from the qualitative interviews were coded using thematic analysis to explore key concepts related to HRQoL and impairment due to PNH symptoms. Data collection began in March 2023; results are based on interim data. Results: Demographic characteristics of the study samples (PNH survey sample: N=31, GP survey sample: N=62, PNH interview sample: N=10) are shown in Table 1. Patients were treated for PNH with eculizumab, pegcetacoplan, or ravulizumab, with an average duration of current PACI treatment of 3.4 years. Compared to the age and sex-matched GP sample, patients with PNH had significantly higher median scores on the PROMIS 29+2 fatigue domain (GP: 48.70 vs PNH: 57.10, p=0.041) and PROMIS Dyspnea Functional Limitations short form (GP: 40.70 vs PNH: 48.60, p=0.036), indicating that patients with PNH experience more fatigue and dyspnea limitations than the GP sample. Patients with PNH also had significantly lower median scores on the PROMIS 29+2 ability to participate in social roles/activities domain (GP: 53.50 vs PNH: 44.20, p=0.013), indicating greater role/activity limitations among patients with PNH. Compared to the GP sample, patients with PNH had numerically lower (i.e., worse) median PROMIS 29+2 cognitive functioning domain scores (GP: 50.00 vs PNH: 46.30, p=0.058) and FACIT Fatigue scores (GP: 39.50 vs PNH: 30.00, p=0.057). Within the PNH sample, statistically significant associations (p&amp;lt;0.05) were observed between fatigue severity and HRQoL/functional impairment for all outcomes except for the PROMIS 29+2 sleep disturbance and cognitive functioning domains (Table 2). Patients with more severe fatigue had worse HRQoL and more functional impairment than patients with less severe fatigue. Interview participants described fatigue-related functional impairments in their physical, social, and cognitive functioning. Fatigue made daily activities (e.g., cooking, cleaning, going for a walk) difficult and sometimes impossible. Planning social activities in advance was also challenging as patients could not predict how they would feel on any given day, and often found they had to miss, postpone, or cancel social engagements. Finally, patients described experiencing “brain fog” including difficulty concentrating, forgetfulness, and delayed cognitive processing. Conclusions: Despite receiving treatment for PNH, patients experienced deficits in areas of HRQoL related to fatigue, participation in social roles, cognitive function, and functional limitations due to dyspnea, relative to a sample of GP adults. During follow-up interviews, patients emphasized the deep and broad impacts that fatigue and cognitive functioning had, making daily activities and their social lives very difficult.

The Influence of Branched-Chain Amino Acid Supplementation on Fatigue and Tryptophan Metabolism After Acute and Chronic Exercise in Older Adults: Protocol for a Pilot Randomized Controlled Trial.

Fatigue is a strong predictor of negative health outcomes in older adults. Kynurenine, a metabolite of tryptophan, is strongly associated with fatigue. Reductions in fatigue are observed with exercise; however, exercise training does not completely alleviate symptoms. Branched-chain amino acids (BCAAs) have been shown to have advantageous effects on exercise performance and compete with kynurenine for transport into the central nervous system. Thus, the combination of BCAA and exercise may exert synergized effects of mental and physical fatigue. Therefore, we hypothesize that BCAA added to exercise will shift kynurenine metabolism toward enhanced synthesis of kynurenic acid, thereby reducing fatigue. This randomized, double-blind, placebo-controlled trial aims to compare the effects of acute (approximately 45 min) and chronic (8 wk) exercise with and without BCAA supplementation on mental and physical fatigue and assess whether the hypothesized outcomes are modulated by changes in kynurenine metabolism in 30 older adults (n=15, 50% per group). Older adults (aged 60-80 y) who do not exercise >2 days per week and self-report fatigue (≥3 on a scale of 1-10) will be recruited. Participants will be randomized to either the exercise+BCAA group or exercise+placebo group. Participants will engage in high-volume, moderate-intensity, whole-body exercise training (aerobic and resistance exercise; either in-person or web-based sessions) 3 times per week for 8 weeks. In addition, participants will consume daily either 100 mg/kg body weight of BCAA (2:1:1 leucine:isoleucine:valine) or placebo (maltodextrin) throughout the 8-week intervention. BCAA and placebo powders will be identical in color and dissolved in 400 mL of water and 2.5 g of a calorie-free water flavor enhancer. Muscle biopsies will be collected before and after the intervention after a 12-hour fast to examine changes in the biomarkers of tryptophan metabolism and inflammation. Our primary outcomes include changes in mental and physical fatigue and metabolism after the 8-week exercise training between the 2 groups. Mental and physical fatigue will be measured before and after the intervention. Mental fatigue will be subjectively assessed through the completion of validated questionnaires. Physical fatigue will be measured by isometric handgrip, 1-repetition maximum, chair rise, 400-meter walk, and cardiopulmonary exercise tests. The study was funded in March 2022, with an anticipated projected data collection period lasting from January 2023 through December 2023. The discovery that kynurenine concentrations are associated with fatigue and are responsive to BCAA supplementation during exercise training could have important implications for the development of future interventions, both lifestyle and pharmacologic, to treat fatigue in older adults. ClinicalTrials.gov NCT05484661; https://www.clinicaltrials.gov/study/NCT05484661. DERR1-10.2196/52199.

Self-Reported Sleepiness, Fatigue and Risk of Obstructive Sleep Apnea Using the STOP BANG Components: Women’s Perspective

Introduction: About 2-4% of adults have obstructive sleep apnoea (OSA), a frequent chronic condition. The disorder is characterised by recurrent bouts of whole or partial collapse of the upper airway, primarily the oropharyngeal tract, while sleeping, which results in a decrease or stoppage of airflow. The aim of the study is to assess the relationship between the self-reported sleepiness, fatigue and the risk of Obstructive Sleep Apnea among the midlife women aged 40 to 65 years Methodology: This was a cross sectional study conducted in the field practice area of rural and urban health and training centre of a tertiary care teaching hospital, Chengalpattu district, Tamilnadu among 380 women aged 40 to 65 years. Results: Mean age of the study population was 49.69 (± 11.2). On risk categorization by STOP-BANG Questionnaire, it was found that 72.9% (277), 26.1% (99) and 1.1% (4) had low, intermediate and high risk for sleep apnea. 16.9% of the study participants had excessive daytime sleepiness. Fatigue severity scale of more than or equal to 36 was seen among 34.5% of the study participants. Conclusion: The STOP-Bang questionnaire has been shown in studies to be a quick, efficient, and accurate OSA screening tool. It can make it easier to allocate resources effectively for detecting and treating OSA that had not yet been recognised.

Dialyzer Performance and Associations in Self-Reported Pruritis and Fatigue: Results from the eMPORA III Trial

Dialyzer Performance and Associations in Self-Reported Pruritis and Fatigue: Results from the eMPORA III Trial

Multimodal agility-based exercise training (MAT) versus strength and endurance training (SET) to improve multiple sclerosis-related fatigue and fatigability during inpatient rehabilitation: a randomized controlled pilot and feasibility study [ReFEx

BackgroundMultimodal agility-based exercise training (MAT) is a group-based exercise training framework for persons with multiple sclerosis (pwMS) with a potential to impact fatigue and fatigability. In a mixed-methods design, this study evaluated the feasibility of implementing MAT in an inpatient rehabilitation setting and the feasibility of a randomized controlled trial (RCT) study protocol with ‘traditional’ strength and endurance training (SET) as an active control condition. Secondarily, preliminary outcome data was acquired.MethodsPwMS with low to moderate disability and self-reported fatigue were randomly allocated to either MAT or SET when starting inpatient rehabilitation (4–6 weeks). The MAT-participants exercised in a group following a MAT-manual (sessions were gym- (5x/week) and pool-based (3x/week)). SET-participants exercised individually 5x/week on a cycle ergometer, and 3x/week on strength training machines. Feasibility assessments focused on processes, resources, management, time, and scientific domains. Assessed clinical outcomes at admission and discharge included perceived fatigue, motor and cognitive fatigability, cognitive performance, motor function, and balance confidence. Perceived fatigue was reassessed 1, 4, and 12 weeks after discharge. Feasibility was determined regarding predetermined progression criteria.ResultsTwenty-two participants were randomized. Both groups performed the minimum number of sessions (> 18), and retention was adequate (73–91%). SET-participants performed more sessions than MAT-participants (30.8 vs. 22.7) and stayed longer in the facility (34.2 vs. 31.6 days). Non-eligibility of admitted pwMS was high (74% non-eligible), mainly due to high EDSS and inability to attend pool-based sessions. Consequently, recruitment (1.8/month) was slower than the predetermined progression criterium. Baseline assessments took longer than required (only 50% completed within 3 days). Short-term fatigue reduction was similar for both groups. Motor fatigability also improved in both groups, whereas cognitive fatigability deteriorated. In MAT, average improvement in walking endurance (43.9 m) exceeded minimal important change values for individuals (> 26.9 m).ConclusionsProgressing to a definitive RCT necessitates adaptation of eligibility criteria. In the present design it will also be difficult to attain similar dosing of interventions. A multicenter RCT focused only on gym-based MAT might be another option to assess the effect of MAT. The primary outcome measure should be able to measure change in perceived fatigue more robustly.Trial registrationGerman Clinical Trials Register: DRKS00023943, date of registration: 23 September 2021.

Mental Fatigue in Patients with Hearing Loss and/or Tinnitus Undergoing Audiological Rehabilitation—A Pilot Study

Background: Both tinnitus and hearing loss are multidimensional. The purpose of this study was to identify and determine the degree of mental fatigue in patients with hearing loss and/or tinnitus participating in audiological rehabilitation, and to examine the self-reported mental fatigue scale (MFS) in this patient group. Methods: Patients undergoing audiological rehabilitation at the Department of Audiology and Neurotology, Karolinska University Hospital, Sweden, between 2011 and 2017 who completed a self-reported MFS questionnaire were investigated. Data on 76 patients were analysed in this pilot study. Patients were also assessed using the Tinnitus Handicap Inventory (THI). Results: The study population had an age range of 38–65 years, and most had normal hearing (37%) or mild to moderate hearing loss (46%). Only 17% had severe to profound hearing loss. A total of 56.5% had tinnitus, of whom 39.5% scored ≥57 on the THI, indicating severe tinnitus, whereas 43.5% reported no tinnitus. The MFS scores, ranging from 13 to 42.5 points, were divided into three severity levels for analysis: 10.5–15, 15.5–20, and ≥20.5. In total, 67% of the patients had MFS scores ≥ 20.5. Importantly, most of the participants (90%) with a THI score ≥ 57 belonged to that group. A significant positive correlation between a high MFS score and severe tinnitus was found. Conclusions: The study reveals that severe mental fatigue is more common in patients with severe tinnitus than sole hearing loss.

Prevalence of fatigue in the general population during the pandemic: cross-sectional study in Geneva

Abstract Background Fatigue is a frequent symptom, the determinants of which are numerous and poorly understood. Fatigue also predicts ischemic heart disease, cancer, physical decline, and mortality. While the COVID-19 pandemic constituted a major stressor, no previous studies have measured the prevalence of fatigue and its determinants since the beginning of the pandemic in a general population. This study aims (1) to assess the prevalence of fatigue among the general population of the canton of Geneva, Switzerland, two years into the pandemic and (2) to analyse its determinants. Methods A cross-sectional population-based study was conducted as part of the Specchio-COVID19 cohort study. Adult participants answered an online health survey between March and May 2022. The main outcome was self-reported fatigue measured by the Chalder Fatigue Questionnaire. Other variables included general and mental health status, quality of life, and sociodemographic data. Multivariable logistic regressions were used to evaluate the determinants of fatigue. Results 4040 participants took part in the survey (participation rate 59%, respondents and non-respondents were comparable). The overall prevalence of fatigue was 31%. Significant determinants of fatigue were depression (aOR 10.49 [6.29-17.50], p &amp;lt; 0.001), diagnosis of a chronic disease in the past year (aOR 1.37 [1.12-1.68], p = 0.002), and an acute health event in the past year (aOR 1.44 [1.08-1.93], p = 0.014). 18-45-year-old people with a chronic disease were more likely to report fatigue (aOR 1.70 [1.04-2.77], p = 0.033). Male gender (aOR 0.72 [0.57-0.92], p = 0.007) or retirement (aOR 0.60 [0.43 - 0.85], p = 0.003) were protective factors. Age, level of education, and income were not significantly associated with fatigue. Conclusions Fatigue was still highly prevalent in the general population two years into the COVID19 pandemic, comparing to regional prepandemic data. The cohort Specchio will monitor the evolution of fatigue after the pandemic. Key messages • Fatigue was still highly prevalent two years into the COVID19 pandemic among the general population in Geneva, comparing to regional prepandemic data. • Longitudinal follow-up is crucial to assess how fatigue is evolving after the pandemic.

Parents underestimate fatigue in younger children aged 5-7 years with asthma but not in older children.

To assess fatigue in children aged 2-17 years with asthma from both child and parent perspectives and describe associated factors. Fatigue scores were self-reported by children aged 5-17 years old and proxy-reported by parents or carers for all children. The Pediatric Quality of Life Inventory Multidimensional Fatigue Scale was used. Fatigue scores ranged from 0 to 100, higher scores meant less fatigue. There were 527 children and parents enrolled. The mean overall fatigue score by self-report was 72.7 ± 15.8 and by proxy report was 75.8 ± 16.3. Self-reported fatigue score was lower in children aged 5-7 years (71.5 ± 15.9) compared to proxy-reported score (76.3 ± 15.5). Proxy and self-reported fatigue scores were similar between parents and older children. Fatigue scores were lower in association with poor asthma control and receipt of social support. Lower self-reported, but not proxy-reported, fatigue score was related to asthma severity. Lower proxy-reported, but not self-reported, fatigue score was related to the child being older and having shortness of breath. Parents underestimated the fatigue of younger children aged 5-7 years, but fatigue scores were similar between parents and older children. Both clinical and social factors are associated with fatigue in children with asthma.

The impact of post-stroke fatigue on work and other everyday life activities for the working age population – a registry-based cohort study

Introduction Life after stroke is a comprehensive area that involves engagement in meaningful everyday activities, including work, and can be adversely affected by post-stroke fatigue. This study investigates post-stroke fatigue, its development over time, and its impact on return to work and other everyday life activities. In addition, we investigated whether post-stroke fatigue could predict functioning in everyday life activities one year after stroke. Material and methods This prospective registry-based study includes 2850 working age (18 – 63 years) patients registered in the Swedish Stroke Register (Riksstroke) during year 2017 and 2018. Post-stroke fatigue and everyday activities were analyzed 3- and 12-months post-stroke. Results The mean age of the included participants was 54 years and the majority, 65%, were men. Three months post-stroke, 43% self-reported fatigue, at 12-months the proportion increased to 48%. About 90% of the patients were independent in basic ADL at 3-month. Dependence in complex activities one year post-stroke was significantly associated with fatigue. Not experiencing fatigue one year after stroke could predict positive functioning in everyday activities, increasing the chance of returning to work (OR = 3.7) and pre-stroke life and everyday activities (OR = 5.7). Conclusion Post-stroke fatigue is a common persistent disability that negatively impacts complex activities; therefore, fatigue needs to be acknowledged and addressed long term after discharge.

Voluntary muscle activation in people with Multiple Sclerosis is reduced across a wide range of forces following maximal effort fatiguing contractions.

Although Multiple Sclerosis (MS) is frequently associated with motor impairment, little is known about how muscle activation is affected with MS. The aim of this study was to use transcranial magnetic stimulation (TMS) and motor nerve stimulation to investigate voluntary muscle activation in people with MS across a range of contraction forces. Ten people with MS (39 ± 7 years) and 10 healthy controls (40 ± 5 years) performed elbow flexions at target contraction forces of 25%, 50%, 75%, 90%, and 100% maximal voluntary contraction (MVC) while electromyography (EMG) of the biceps brachii was recorded. Sustained elbow flexion MVCs were then performed until force declined to 60% of baseline MVC, where the target contraction forces were again examined but after the sustained MVC. Following the sustained MVC there was a reduction in biceps EMG amplitude (P < 0.01) and motor cortical voluntary activation (P < 0.01) for the MS group across all contraction intensities. There was also an increase in the rate of torque development for motor nerve resting twitches in the MS group following the sustained MVC (P = 0.03). Despite the MS group reporting higher Fatigue Severity Scale scores (P < 0.01), disease duration was a better predictor of muscle activation for the MS group (r = -0.757, P = 0.01). These findings indicate that voluntary muscle activation is compromised in people with MS following maximal effort contractions, which may be associated with disease duration rather than self-reports of fatigue.