The effect of graded exercise therapy on fatigue in people with serious respiratory illness: a systematic review.

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.

Constructing a picture of fatigue in the context of cancer: assessment of construct overlap in common fatigue scales.

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.

Chronic thyrotoxic myopathy development is associated with thyroid hormone sensitivity index, predicted by lower-limb fatigue and the squat-up test.

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 FT3 (TFQIFT3) and the parametric TFQIFT3 (PTFQIFT3), TFQIFT4, and PTFQIFT4 were positively associated with CTM risk by using inverse probability of treatment weighting multivariate logistic regression. For each 1-SD increase in TFQIFT3 and PTFQIFT3, TFQIFT4 and PTFQIFT4, 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.

Combining patient-reported outcome measures to screen for active disease in rheumatoid arthritis and psoriatic arthritis.

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.

Patient-reported outcome measures for lupus nephritis: content validity of LupusQoL and FACIT-Fatigue.

BACKGROUND: Lupus nephritis (LN), a severe organ manifestation of systemic lupus erythematosus (SLE), significantly impacts health-related quality of life (HRQoL). Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) and Lupus Quality of Life (LupusQoL) have been validated to measure HRQoL in SLE, but not specifically in LN. Patient-reported symptoms of LN are not well-reported. We assessed the content validity and relevance of these measures in evaluating patients with LN and their LN-related experiences. METHODS: This qualitative, interview-based study enrolled patients with LN from three US sites from a larger, retrospective survey study. The interview comprised an open-ended concept elicitation part and a more structured cognitive part. Concept elicitation was used to identify relevant themes describing the patients' experiences. Patients were asked to describe their LN-related symptoms, the severity and impact of those symptoms and their satisfaction with treatment. A cognitive interview approach evaluated the appropriate understanding of the items, instructions, and response options and asked patients about their understanding of the FACIT-Fatigue or LupusQoL measures, their relevance to the condition, and any aspects of confusion or need for better clarity of the questionnaires. All interviews were recorded and transcribed. The concept elicitation data were coded, while the cognitive interview data were tabulated to present the participants' responses next to the interview questions to support the evaluation of their understanding of the questionnaire items. RESULTS: Overall, 10 patients participated in FACIT-Fatigue and another 10 in LupusQoL interviews; 18 patients were female, 10 were Black (self-reported) and 17 were receiving maintenance treatment for LN with stable disease activity. When patients recalled their symptoms, 670 expressions of varying symptoms were reported. All patients described pain, discomfort, and energy-related symptoms. Urinary frequency and non-joint swelling were most frequently attributed to LN rather than SLE. Patients felt the questions asked in the FACIT-Fatigue and LupusQoL surveys were relevant to their LN experience. CONCLUSIONS: The symptoms reported by patients with LN were consistent with symptoms reported by the overall SLE population. However, patients indicated that some symptoms of LN were more profound than symptoms of SLE alone, affecting a broad range of areas of daily life activity and resulting in a higher burden on their HRQoL. FACIT-Fatigue and LupusQoL demonstrated content relevance as meaningful tools for patients with LN. However, further quantitative data collection is needed to ensure that these patient-reported outcome tools demonstrate good measurement properties in an LN population.

Long COVID or Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) and the Urgent Need to Identify Diagnostic Biomarkers and Risk Factors.

Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), also known as post-COVID-19 condition or post-COVID syndrome, can affect anyone infected with SARS-CoV-2, regardless of age or the severity of the initial symptoms of COVID-19. Long COVID/PASC is the continuation or development of new symptoms after three months from the initial SARS-CoV-2 infection, which lasts for at least two months and has no other identifiable cause. Long COVID/PASC occurs in 10-20% of patients infected with SARS-CoV-2. The most common symptoms include fatigue, cognitive impairment (brain fog), and shortness of breath. However, more than 200 symptoms have been reported. No phenotypic or diagnostic biomarkers have been identified for developing long COVID/PASC, which is a multisystem disorder that can present with isolated or combined respiratory, hematological, immunological, cardiovascular, and neuropsychiatric symptoms. There is no cure. Therefore, individualized patient management requires a multidisciplinary clinical approach. Because millions of people have had and continue to have COVID-19, even in the era of vaccination and antiviral therapies, long COVID/PASC is now and will increasingly become a health and economic burden that the world must prepare for. Almost five years from the beginning of the COVID-19 pandemic, this article aims to review what is currently known about long COVID/PASC, the anticipated increasing global health burden, and why there is still an urgent need to identify diagnostic biomarkers and risk factors to improve prevention and treatment.

[Fatigue feature extraction and classification algorithm of forehead single-channel electroencephalography signals].

Aiming at the problem that the feature extraction ability of forehead single-channel electroencephalography (EEG) signals is insufficient, which leads to decreased fatigue detection accuracy, a fatigue feature extraction and classification algorithm based on supervised contrastive learning is proposed. Firstly, the raw signals are filtered by empirical modal decomposition to improve the signal-to-noise ratio. Secondly, considering the limitation of the one-dimensional signal in information expression, overlapping sampling is used to transform the signal into a two-dimensional structure, and simultaneously express the short-term and long-term changes of the signal. The feature extraction network is constructed by depthwise separable convolution to accelerate model operation. Finally, the model is globally optimized by combining the supervised contrastive loss and the mean square error loss. Experiments show that the average accuracy of the algorithm for classifying three fatigue states can reach 75.80%, which is greatly improved compared with other advanced algorithms, and the accuracy and feasibility of fatigue detection by single-channel EEG signals are significantly improved. The results provide strong support for the application of single-channel EEG signals, and also provide a new idea for fatigue detection research.

Research on fatigue detection of flight trainees based on face EMF feature model combination with PSO-CNN algorithm.

Even though the capability of aircraft manufacturing has improved, human factors still play a pivotal role in flight accidents. For example, fatigue-related accidents are a common factor in human-led accidents. Hence, pilots' precise fatigue detections could help increase the flight safety of airplanes. The article suggests a model to recognize fatigue by implementing the convolutional neural network (CNN) by implementing flight trainees' face attributions. First, the flight trainees' face attributions are derived by a method called the land-air call process when the flight simulation is run. Then, sixty-eight points of face attributions are detected by employing the Dlib package. Fatigue attribution points were derived based on the face attribution points to construct a model called EMF to detect face fatigue. Finally, the proposed PSO-CNN algorithm is implemented to learn and train the dataset, and the network algorithm achieves a recognition ratio of 93.9% on the test set, which can efficiently pinpoint the flight trainees' fatigue level. Also, the reliability of the proposed algorithm is validated by comparing two machine learning models.

Development and validation of a nomogram to estimate fatigue probability in hemodialysis patients.

OBJECTIVE: This study aims to investigate the factors that influence fatigue in hemodialysis (HD) patients and to develop and validate a nomogram to estimate the probability of fatigue in this population. METHODS: This cross-sectional study collected 453 patients who underwent HD at the tertiary hospital in Hubei, China, from April to December 2023. They were randomly divided into a 70% training group (n = 316) and a 30% validation group (n = 137). In the training set, factors influencing fatigue were screened using multivariate logistic regression analysis, and a nomogram was developed to estimate fatigue probability in HD patients. The discrimination and calibration of the nomogram were validated in both the training and validation sets through the area under the receiver operating characteristic (ROC) curve (AUC) and the Hosmer-Lemeshow (H-L) test. RESULTS: In the training group, logistic regression showed that age, dialysis vintage, inter-dialysis weight gain, hemoglobin, depression, insomnia, and social support were variables associated with fatigue in HD patients. Based on these factors, a nomogram for assessing fatigue probability in HD patients was developed. The AUC was 0.955 (95% CI: 0.932-0.977) and 0.979 (95% CI: 0.961-0.997) in the training and validation sets. The results from the H-L test indicated a good fit. CONCLUSION: The nomogram can evaluate fatigue probability in HD patients and may serve as a convenient clinical tool.

Urdu translation and cross-cultural validation of neurological fatigue index on post stroke.

BACKGROUND: The Neurological Fatigue Index (NFI) is the instrument used to evaluate stroke patients' fatigue. There was no Urdu version of NFI available officially. OBJECTIVE: This study aimed to translate the Neurological Fatigue Index into Urdu and to determine the validity and reliability of Urdu NFI among stroke patients. METHODOLOGY: It is a cross-cultural validation study. According to international guidelines in phase I, a process of translation was carried out. In phase II, using the sample of 120 participants, validity and reliability of the Urdu version of the Neurological Fatigue Index scale was conducted. The Urdu version's content validity, convergent/concurrent validity, test-retest reliability, and internal consistency were determined. The latest version of SPSS was used for the data analysis. RESULTS: The Urdu version of NFI was drafted after the expert's review. The content validity index was used to analyze the content validity. The reliability and validity of the Urdu version NFI were evaluated by calculating Cronbach's alpha (α = 0.86), and intra-class correlation coefficient (ICC = 0.823). Correlations with other scales were the fatigue Severity Scale (FSS) (r = 0.76), Mental Fatigue Scale (MFS) (r = 0.68), Beck Depression Inventory (BDI) (r = 0.53) and Epworth Sleepiness Scale (ESS) (r = 0.47). CONCLUSION: The Urdu Version was linguistically acceptable for the fatigue assessment in post-stroke patients. It showed good content validity, convergent/concurrent validity, internal consistency, and test-retest reliability.

Designing a practical fatigue detection system: A review on recent developments and challenges.

INTRODUCTION: Fatigue is considered to have a life-threatening effect on human health and it has been an active field of research in different sectors. Deploying wearable physiological sensors helps to detect the level of fatigue objectively without any concern of bias in subjective assessment and interfering with work. METHODS: This paper provides an in-depth review of fatigue detection approaches using physiological signals to pinpoint their main achievements, identify research gaps, and recommend avenues for future research. The review results are presented under three headings, including: signal modality, experimental environments, and fatigue detection models. Fatigue detection studies are first divided based on signal modality into uni-modal and multi-modal approaches. Then, the experimental environments utilized for fatigue data collection are critically analyzed. At the end, the machine learning models used for the classification of fatigue state are reviewed. PRACTICAL APPLICATIONS: The directions for future research are provided based on critical analysis of past studies. Finally, the challenges of objective fatigue detection in the real-world scenario are discussed.

The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale in patients with axial spondyloarthritis: psychometric properties and clinically meaningful thresholds for interpretation.

BACKGROUND: Fatigue is an important symptom for most patients with axial spondyloarthritis (axSpA). The FACIT-Fatigue is a 13-item patient-reported outcome (PRO) instrument that has been used in axSpA clinical trials to measure fatigue severity and impact on daily activities. However, the psychometric properties of the FACIT-Fatigue are not fully evaluated across the entire spectrum of axSpA including non-radiographic axSpA (nr-axSpA) and radiographic axSpA (r-axSpA). This study determined: (1) the psychometric properties of the FACIT-Fatigue in nr-axSpA, r-axSpA, and the broad axSpA population and (2) FACIT-Fatigue scores representing meaningful within-patient change (MWPC), meaningful between-group differences, and cross-sectional severity bands. METHODS: Data from two Phase 3 trials in adults with nr-axSpA (BE MOBILE 1; N = 254) and r-axSpA (BE MOBILE 2; N = 332) were analyzed pooled and separately to assess the psychometric properties of the FACIT-Fatigue. MWPC and meaningful between-group difference estimates were derived using anchor-based and distribution-based methods. Cross-sectional fatigue severity bands were estimated using logistic regression analysis. RESULTS: The FACIT-Fatigue presented good internal consistency, adequate convergent and known-groups validity, and was sensitive to change over time across the full axSpA spectrum. A 5-11-point increase in FACIT-Fatigue score was estimated to represent a MWPC, with an 8-point increase selected as the responder definition. A 2.14-5.34-point difference in FACIT-Fatigue score change over a 16-week period was estimated to represent a small-to-medium meaningful between-group difference. FACIT-Fatigue score severity bands were defined as: none or minimal (>40), mild (>30 to ≤40), moderate (>21 to ≤30), and severe (≤21). CONCLUSIONS: These findings support the use of the FACIT-Fatigue as a fit-for-purpose measure to assess fatigue-related treatment benefit in axSpA clinical trials. The proposed score estimates and thresholds can guide FACIT-Fatigue score interpretation across the full axSpA spectrum. TRIAL REGISTRATION: ClinicalTrials.Gov, NCT03928704. Registered 26 April 2019-Retrospectively registered, https://classic. CLINICALTRIALS: gov/ct2/show/NCT03928704 . CLINICALTRIALS: Gov, NCT03928743. Registered 26 April 2019-Retrospectively registered, https://classic. CLINICALTRIALS: gov/ct2/show/NCT03928743 .

Six-minute walk test as outcome measure of fatigability in adults with spinal muscular atrophy treated with nusinersen.

INTRODUCTION/AIMS: Fatigue (subjective perception) and fatigability (objective motor performance worsening) are relevant aspects of disability in individuals with spinal muscular atrophy (SMA). The effect of nusinersen on fatigability in SMA patients has been investigated with conflicting results. We aimed to evaluate this in adult with SMA3. METHODS: We conducted a multicenter retrospective cohort study, including adult ambulant patients with SMA3, data available on 6-minute walk test (6MWT) and Hammersmith Functional Motor Scale-Expanded (HFMSE) at baseline and at least at 6 months of treatment with nusinersen. We investigated fatigability, estimated as 10% or higher decrease in walked distance between the first and sixth minute of the 6MWT, at baseline and over the 14-month follow-up. RESULTS: Forty-eight patients (56% females) were included. The 6MWT improved after 6, 10, and 14 months of treatment (p < 0.05). Of the 27 patients who completed the entire follow-up, 37% improved (6MWT distance increase ≥30 m), 48.2% remained stable, and 14.8% worsened (6MWT distance decline ≥30 m). Fatigability was found at baseline in 26/38 (68%) patients and confirmed at subsequent time points (p < 0.05) without any significant change over the treatment period. There was no correlation between fatigability and SMN2 copy number, sex, age at disease onset, age at baseline, nor with 6MWT total distance and baseline HFMSE score. DISCUSSION: Fatigability was detected at baseline in approximately 2/3 of SMA3 walker patients, without any correlation with clinical features, included motor performance. No effect on fatigability was observed during the 14-month treatment period with nusinersen.

Construct validity of PROMIS pain interference, fatigue, and physical function as patient-reported outcomes in adults with idiopathic inflammatory myopathies: An international study from the OMERACT myositis working group.

BACKGROUND: Validated patient-reported outcome measures to assess disease impact in patients with adult idiopathic inflammatory myopathies (IIMs) are needed. The objective of this study was to assess the construct validity of PROMIS Pain Interference, Fatigue, and Physical Function measures in comparison with core disease activity measures. METHODS: Adults with IIM, excluding inclusion body myositis, from OMERACT Myositis Working Group (MWG) clinic sites completed PROMIS Short Form v1.0-Pain Interference 6a, PROMIS Short Form v1.0-Fatigue 7a, and PROMIS Short Form v2.0-Physical Function 8b measures. Core disease activity measures including patient and physician global disease activity assessments, manual muscle testing, serum creatine kinase activity, and Health Assessment Questionnaire Disability Index (HAQ-DI) were simultaneously assessed. To evaluate construct validity, a priori hypotheses for the expected correlations between PROMIS measures, age, and core disease measures were determined by >70 % agreement among MWG members and were compared against observed Pearson's correlations. Internal consistency of items and floor or ceiling effects for the PROMIS measures were also assessed. Subgroup analysis according to IIM subtype (dermatomyositis vs. non-dermatomyositis IIM) was performed. RESULTS: 135 adults with IIM from 5 countries across North America, Europe, Asia, and Australia were included. For construct validity, a priori hypotheses were confirmed for 5 of 6 (83 %) PROMIS Pain Interference, 4 of 5 (80 %) PROMIS Fatigue, and 3 of 4 (75 %) PROMIS Physical Function correlations. Internal consistency was high for each PROMIS measure (Cronbach's alpha >0.9). Ceiling effects were observed only for PROMIS Pain Interference, with low/no pain in 29 % of patients. Subgroup analysis between dermatomyositis (n = 65) and non-dermatomyositis (n = 70) subtypes demonstrated similar correlations between PROMIS measures and disease activity measures. CONCLUSIONS: PROMIS Short Form v1.0-Pain Interference 6a, PROMIS Short Form v1.0-Fatigue 7a, and PROMIS Short Form v2.0-Physical Function 8b measures demonstrate strong construct validity when compared to core disease activity measures in IIM, with consistent results across IIM subtypes. These findings support the use of these selected PROMIS measures to assess core domains of interest for measuring life impact in IIMs.

[The 509th case: fatigue, sleepiness, mood disorder, and hypothyroidism].

A 28-year-old woman presented with a 4-year history of fatigue and sleepiness and was found to have central hypothyroidism and mood disorder. The patient had normal thyroid volume and did not show any other pituitary axis involvement. Over the course of the disease, her symptom improvement matched with the free thyroxine (FT4) rebound and the adjustment of antipsychotic medication. The patient's grandmother had central hypothyroidism, and her mother and uncle had lowered or inappropriately normal thyroid stimulating hormone. Hence, genetic involvement was highly suspected, but whole exon sequencing did not reveal a pathogenic variant. Levothyroxine tablets were prescribed to maintain a normal median level of FT4, and mood disorder medications were adjusted by specialists. Isolated central hypothyroidism is extremely rare, and we report this case aiming to raise awareness of this condition.

Cardiopulmonary exercise testing in long covid shows the presence of dysautonomia or chronotropic incompetence independent of subjective exercise intolerance and fatigue.

BACKGROUND: After COVID-19 infection, 10-20% of patients suffer from varying symptoms lasting more than 12 weeks (Long COVID, LC). Exercise intolerance and fatigue are common in LC. The aim was to measure the maximal exercise capacity of the LC patients with these symptoms and to analyze whether this capacity was related to heart rate (HR) responses at rest and during exercise and recovery, to find out possible sympathetic overactivity, dysautonomia or chronotropic incompetence. METHODS: Cardiopulmonary exercise test was conducted on 101 LC patients, who were admitted to exercise testing. The majority of them (86%) had been treated at home during their acute COVID-19 infection. Peak oxygen uptake (VO2peak), maximal power during the last 4 min of exercise (Wlast4), HRs, and other exercise test variables were compared between those with or without subjective exercise intolerance, fatigue, or both. RESULTS: The measurements were performed in mean 12.7 months (SD 5.75) after COVID-19 infection in patients with exercise intolerance (group EI, 19 patients), fatigue (group F, 31 patients), their combination (group EI + F, 37 patients), or neither (group N, 14 patients). Exercise capacity was, in the mean, normal in all symptom groups and did not significantly differ among them. HRs were higher in group EI + F than in group N at maximum exercise (169/min vs. 158/min, p = 0.034) and 10 min after exercise (104/min vs. 87/min, p = 0.028). Independent of symptoms, 12 patients filled the criteria of dysautonomia associated with slightly decreased Wlast4 (73% vs. 91% of sex, age, height, and weight-based reference values p = 0.017) and 13 filled the criteria of chronotropic incompetence with the lowest Wlast4 (63% vs. 93%, p < 0.001), VO2peak (70% vs. 94%, p < 0.001), the lowest increase of systolic blood pressure (50 mmHg vs. 67 mmHg, p = 0.001), and the greatest prevalence of slight ECG-findings (p = 0.017) compared to patients without these features. The highest prevalence of chronotropic incompetence was seen in the group N (p = 0.022). CONCLUSIONS: This study on LC patients with different symptoms showed that cardiopulmonary exercise capacity was in mean normal, with increased sympathetic activity in most patients. However, we identified subgroups with dysautonomia or chronotropic incompetence with a lowered exercise capacity as measured by Wlast4 or VO2peak. Subjective exercise intolerance and fatigue poorly foresaw the level of exercise capacity. The results could be used to plan the rehabilitation from LC and for selection of the patients suitable for it.

Decoding IBS: a machine learning approach to psychological distress and gut-brain interaction.

PURPOSE: Irritable bowel syndrome (IBS) is a diagnosis defined by gastrointestinal (GI) symptoms like abdominal pain and changes associated with defecation. The condition is classified as a disorder of the gut-brain interaction (DGBI), and patients with IBS commonly experience psychological distress. The present study focuses on this distress, defined from reports of fatigue, anxiety, depression, sleep disturbances, and performance on cognitive tests. The aim was to investigate the joint contribution of these features of psychological distress in predicting IBS versus healthy controls (HCs) and to disentangle clinically meaningful subgroups of IBS patients. METHODS: IBS patients ( n = 49 ) and HCs ( n = 28 ) completed the Chalder Fatigue Scale (CFQ), the Hamilton Anxiety and Depression Scale (HADS), and the Bergen Insomnia Scale (BIS), and performed tests of memory function and attention from the Repeatable Battery Assessing Neuropsychological Symptoms (RBANS). An initial exploratory data analysis was followed by supervised (Random Forest) and unsupervised (K-means) classification procedures. RESULTS: The explorative data analysis showed that the group of IBS patients obtained significantly more severe scores than HCs on all included measures, with the strongest pairwise correlation between fatigue and a quality measure of sleep disturbances. The supervised classification model correctly predicted belongings to the IBS group in 80% of the cases in a test set of unseen data. Two methods for calculating feature importance in the test set gave mental and physical fatigue and anxiety the strongest weights. An unsupervised procedure with K = 3 showed that one cluster contained 24% of the patients and all but two HCs. In the two other clusters, their IBS members were overall more impaired, with the following differences. One of the two clusters showed more severe cognitive problems and anxiety symptoms than the other, which experienced more severe problems related to the quality of sleep and fatigue. The three clusters were not different on a severity measure of IBS and age. CONCLUSION: The results showed that psychological distress is an integral component of IBS symptomatology. The study should inspire future longitudinal studies to further dissect clinical patterns of IBS to improve the assessment and personalized treatment for this and other patient groups defined as disorders of the gut-brain interaction. The project is registered at https://classic. CLINICALTRIALS: gov/ct2/show/NCT04296552 20/05/2019.

The burden and determinants of fatigue in incident and prevalent systemic sclerosis.

OBJECTIVES: To investigate the burden and clinical associations of fatigue in systemic sclerosis (SSc) as measured by FACIT-Fatigue scores. METHODS: Australian Scleroderma Cohort Study participants with ≥1 FACIT-Fatigue score were included. Participants were divided into those with incident SSc (≤5 years SSc duration at recruitment and FACIT-Fatigue score recorded within 5 years of disease onset) or prevalent SSc (first FACIT-Fatigue score recorded >5 years after SSc onset). Generalised estimating equations were used to model change in FACIT-Fatigue scores over time, expressed as an increasing (improving) or decreasing (worsening) score. RESULTS: Of 859 participants, 215 had incident SSc and 644 prevalent SSc. First-recorded FACIT-Fatigue scores were similar in those with incident (37 units, IQR 25-45.5) and prevalent SSc (36 units, IQR 23-44; p=0.17), as were lowest-ever recorded FACIT-Fatigue scores (incident 23 units; prevalent 22 units, p=0.75). In incident SSc, higher skin scores (regression coefficient (RC) -1.5 units, 95%CI -2.3 to -0.8), PAH (RC -8.2, 95%CI -16.5 to 0.1) and reduced left ventricular function (RC -10.6, 95%CI -18.3 to -2.8) were associated with more severe fatigue. In prevalent SSc, higher skin scores (RC -0.6, 95%CI -1.3 to 0), gastrointestinal symptoms (RC -6.6, 95%CI -9.0 to -4.2), hypoalbuminaemia (RC -2.8, 95%CI -5.0 to -0.7), BMI<18.5kg/m2 (RC -6.3, 95%CI -10.3 to -2.2), raised CRP (RC -3.1, 95%CI -4.7 to -1.5), and anaemia (RC -1.7, 95%CI -3.5 to 0.1) were associated with more severe fatigue. CONCLUSIONS: The burden of fatigue is substantial in both incident and prevalent SSc. Cardiopulmonary and gastrointestinal involvement are associated with worse fatigue.

Evaluating the Construct Validity of the Charité Alarm Fatigue Questionnaire using Confirmatory Factor Analysis.

Background: The Charité Alarm Fatigue Questionnaire (CAFQa) is a 9-item questionnaire that aims to standardize how alarm fatigue in nurses and physicians is measured. We previously hypothesized that it has 2 correlated scales, one on the psychosomatic effects of alarm fatigue and the other on staff's coping strategies in working with alarms. Objective: We aimed to validate the hypothesized structure of the CAFQa and thus underpin the instrument's construct validity. Methods: We conducted 2 independent studies with nurses and physicians from intensive care units in Germany (study 1: n=265; study 2: n=1212). Responses to the questionnaire were analyzed using confirmatory factor analysis with the unweighted least-squares algorithm based on polychoric covariances. Convergent validity was assessed by participants' estimation of their own alarm fatigue and exposure to false alarms as a percentage. Results: In both studies, the χ2 test reached statistical significance (study 1: χ226=44.9; P=.01; study 2: χ226=92.4; P<.001). Other fit indices suggested a good model fit (in both studies: root mean square error of approximation <0.05, standardized root mean squared residual <0.08, relative noncentrality index >0.95, Tucker-Lewis index >0.95, and comparative fit index >0.995). Participants' mean scores correlated moderately with self-reported alarm fatigue (study 1: r=0.45; study 2: r=0.53) and weakly with self-perceived exposure to false alarms (study 1: r=0.3; study 2: r=0.33). Conclusions: The questionnaire measures the construct of alarm fatigue as proposed in our previous study. Researchers and clinicians can rely on the CAFQa to measure the alarm fatigue of nurses and physicians.