Iron deficiency, anemia, and patient-reported outcomes in kidney transplant recipients.

Kidney transplant recipients (KTRs) experience more fatigue, anxiety, and depressive symptoms and lower concentration and health-related quality of life (HRQoL) compared with the general population. Anemia is a potential cause that is well-recognized and treated. Iron deficiency, however, is often unrecognized, despite its potential detrimental effects related to and unrelated to anemia. We investigated the interplay of anemia, iron deficiency, and patient-reported outcomes in 814 outpatient KTRs (62% male, age 56 ± 13 years) enrolled in the TransplantLines Biobank and Cohort Study (Groningen, The Netherlands). In total, 28% had iron deficiency (ie, transferrin saturation < 20% and ferritin < 100 µg/L), and 29% had anemia (World Health Organization criteria). In linear regression analyses, iron deficiency, but not anemia, was associated with more fatigue, worse concentration, lower wellbeing, more anxiety, more depressive symptoms, and lower HRQoL, independent of age, sex, estimated glomerular filtration rate, anemia, and other potential confounders. In the fully adjusted logistic regression models, iron deficiency was associated with an estimated 53% higher risk of severe fatigue, a 100% higher risk of major depressive symptoms, and a 51% higher chance of being at risk for sick leave/work disability. Clinical trials are needed to investigate the effect of iron deficiency correction on patient-reported outcomes and HRQoL in KTRs.

The validation of Chinese version of workplace PERMA-profiler and the association between workplace well-being and fatigue.

BACKGROUND: Well-being is an important issue in workplace. One of these assessment tools of well-being, Workplace PERMA Profiler, is based on Seligman's five dimensions well-being. Prolonged fatigue may last for a long time, leading a great impact on both employees and enterprises. However, rare studies about the association between well-being and fatigue had been investigated. Our aim is to establish the Chinese version Profiler, and to discovery the association between workplace well-being and fatigue. METHODS: The Chinese version was established according to International Society of Pharmacoeconomics and Outcomes Research (ISPOR) task force guidelines. In the study, researchers employed simple random sampling by approaching individuals undergoing health checkups or receiving workplace health services, inviting them to participate in a questionnaire-based interview. Prolonged Fatigue was evaluated by Checklist Individual Strength (CIS). The reliability was evaluated by Cronbach's alphas, Intra-class Correlation Coefficients (ICCs), and measurement errors. Moreover, confirmatory factor analysis and correlational analyses were assessed for the validity. RESULTS: The analyses included 312 Chinese workers. Cronbach's alphas of the Chinese version ranged from 0.69 to 0.93, while the ICC ranged from 0.70 to 0.92. The 5-factor model of confirmatory factor analysis revealed a nearly appropriate fit (χ2 (82) = 346.560, Comparative Fit Index [CFI] = 0.887, Tucker-Lewis Index [TLI] = 0.855, Root Mean Square Error of Approximation [RMSEA] = 0.114, Standardized Root Mean Square Residual [SRMR] = 0.060). Moreover, the CIS and its four dimensions were significantly and negatively associated with the Positive Emotion, while they are positively associated with Engagement dimension except CIS-Motivation dimension. CONCLUSION: The Chinese version Workplace PERMA-Profiler indicate nice reliability and validity. Furthermore, all CIS dimensions were negatively influenced by Positive Emotion, while commonly positively associated with Engagement.

Response Shift After Cognitive Behavioral Therapy Targeting Severe Fatigue: Explorative Analysis of Three Randomized Controlled Trials.

BACKGROUND: Cognitive behavioral therapy (CBT) is an evidence-based intervention for severe fatigue. Changes in patients' fatigue scores following CBT might reflect not only the intended relief in fatigue but also response shift, a change in the meaning of patients' self-evaluation. Objectives were to (1) identify the occurrence of response shift in patients undergoing CBT, (2) determine the impact of response shift on the intervention effect, and (3) investigate whether changes in fatigue-related cognitions and perceptions, targeted during CBT, are associated with response shift. METHODS: Data of three randomized controlled trials testing the efficacy of CBT in individuals with chronic fatigue syndrome (CFS, n = 222), cancer (n = 123), and diabetes (n = 107) were re-analyzed. Fatigue severity was measured with 8 items from the Checklist Individual Strength, a valid and widely used self-report questionnaire. Structural equation modelling was applied to assess lack of longitudinal measurement invariance, as indication of response shift. RESULTS: As expected, in all three trials, response shift was indicated in the CBT groups, not the control groups. Response shift through reprioritization was indicated for the items "Physically, I feel exhausted" (CFS) and "I tire easily" (cancer, diabetes), which became less vs. more important to the measurement of fatigue, respectively. However, this did not affect the intervention effects. Some changes in cognitions and perceptions were associated with the response shifts. CONCLUSIONS: CBT seems to induce response shift through reprioritization across patient groups, but its occurrence does not affect the intervention effect. Future research should corroborate these findings and investigate whether patients indeed change their understanding of fatigue.

The checklist individual strength (CIS20-R) in patients with amyotrophic lateral sclerosis - a longitudinal study.

OBJECTIVES: Fatigue may be underestimated symptom in amyotrophic lateral sclerosis (ALS). The self-administered checklist individual strength (CIS20-R) was used to measure both physical and mental fatigue in ALS. MATERIALS AND METHODS: Fatigue was measured in 51 consecutive patients with ALS using the fatigue severity scale (FSS) and the CIS20-R (four dimensions: subjective fatigue experience, concentration, motivation, activity). The questionnaire scores were compared with disease and progression parameters [revised ALS functional rating scale (ALS-FRS-R), MRC sum score, slow vital capacity (slow VC)]. Patients had follow-ups at six and 12 months. RESULTS: At baseline (mean age: 57.9 years ± 12.3, mean disease duration: 15.8 months ± 12.7) clinical relevant fatigue was seen in 49% in FSS and 40% in CIS20-R. FSS and CIS20-R (except the subscale for concentration) were steadily increasing in the course of the disease. CIS1 (subjective fatigue) but not FSS showed a correlation to the ALS-FRS-R and the progression of the ALS-FRS-R after 12 months. There was a moderate positive correlation between FSS and CIS20-R. CONCLUSIONS: The CIS20-R is a sensitive tool to detect clinically relevant fatigue in early stages of ALS. Both physical and mental (motivation) dimensions of fatigue steadily increase during the course of the disease in ALS.

Minimal and robust clinically important differences for patient-reported outcome measures of fatigue in chronic stroke survivors after fatigue rehabilitation.

PURPOSE: The minimal and robust clinically important difference (MCID and/or RCID) are essential in assessing the clinical significance of multidimensional fatigue inventory-20 and checklist of individual strength-fatigue subscale questionnaires changes scores. This is the first study to determine the MCID and RCID of these questionnaires in chronic stroke survivors. MATERIALS AND METHODS: A total of 125 participants in an observational cohort study completed MFI-20 and CIS-fs before and after receiving multidisciplinary rehabilitation (cognitive behavioral therapy, graded exercise and adaptive pacing therapy). Anchor-based MCIDs and RCIDs were calculated using the mean change, the mean difference and the receiver operating characteristics methods. To evaluate the accordance between of distribution-based MCIDs (1 SD, ½ SD, SEM, 1.96 SEM and MDC values) with anchored values, the accuracy, sensitivity, specificity and Youden's index were calculated. RESULTS: The anchored MCIDs were between -5 to -7.33 for MFI-20 and -4.87 to -5.40 for CIS-fs. The anchored RCIDs ranged from -5 to -13.88 and -6 to -9.88 for MFI-20 and CIS-fs, respectively. The values of ½ SD and SEM for CIS-fs were consistent with anchored RCIDs. CONCLUSIONS: The estimated MCIDs and RCIDs of MFI-20 and CIS-fs can help researchers and clinicians interpret their chronic stroke patient data.

The Multidimensional Fatigue Inventory-20 (MFI-20) And Checklist Individual Strength-20 (CIS-20) Measures Are Two Important And Valid Instruments For Measuring Fatigue In Patients With Chronic Stroke.The Identified Minimal Clinically Important Differences (MCID) And Robust Clinically Important Difference In The Current Study Can Assist Clinicians In The Clinical Interpretation Of Fatigue Changes Observed In MFI-20 And CIS-20 Scores.The MCID Obtained In This Study Can Be Useful In Determining The Proportion Of Patients Who Benefit From Fatigue Treatment In Stroke Rehabilitation.

Assessing fatigue in childhood cancer survivors: Psychometric properties of the Checklist Individual Strength and the Short Fatigue Questionnaire--a DCCSS LATER study.

BACKGROUND: Fatigue is often reported by patients with childhood cancer both during and after cancer treatment. Several instruments to measure fatigue exist, although none are specifically validated for use in childhood cancer survivors (CCS). The aim of the current study was to present norm values and psychometric properties of the Checklist Individual Strength (CIS) and Short Fatigue Questionnaire (SFQ) in a nationwide cohort of CCS. METHODS: In total, 2073 participants were included from the Dutch Childhood Cancer Survivor Study (DCCSS) LATER cohort. Normative data, construct validity, structural validity, and internal consistency were calculated for the CIS and SFQ. In addition, reliability and a cutoff score to indicate severe fatigue were determined for the SFQ. RESULTS: Correlations between CIS/SFQ and vitality measures asking about fatigue were high (>0.8). Correlations between CIS/SFQ and measures of different constructs (sleep, depressive emotions, and role functioning emotional) were moderate (0.4-0.6). Confirmatory factor analysis resulted in a four-factor solution for the CIS and a one-factor solution for the SFQ with Cronbach's alpha for each (sub)scale showing good to excellent values (>0.8). Test-retest reliability of the SFQ was adequate (Pearson's correlation = 0.88; ICC = 0.946; weighted Cohen's kappa item scores ranged 0.31-0.50) and a cut-off score of 18 showed good sensitivity and specificity scores (92.6% and 91.3%, respectively). CONCLUSION: The current study shows that the SFQ is a good instrument to screen for severe fatigue in CCS. The CIS can be used as a tool to assess the multiple fatigue dimensions in CCS.

Using smartphone-based ecological momentary assessment and personalized feedback for patients with chronic cancer-related fatigue: A proof-of-concept study.

Introduction: Chronic cancer-related fatigue (CCRF) is a complex multidimensional problem warranting person-centered care. Providing patients and therapists personalized feedback based on network analysis applied to ecological momentary assessment (EMA) data could facilitate case conceptualization in psycho-oncological care. The aim was to explore patients' and therapists' experiences of using an EMA app and personalized feedback based on network theory to aid case conceptualization in psycho-oncological care. Methods: A n = 5 proof-of-concept study was implemented in routine psycho-oncological care. We purposively selected adult cancer patients suffering from severe CCRF who were on the waitlist for psycho-oncological care. During a 3-week period participants filled out the EMA app Energy InSight (fatigue, mood, activity, responding, and context) five times a day. Participants received a descriptive and network feedback report, which they reflected upon during the first therapy sessions. Thematic analysis was used to analyze user experiences. Results: Patients experienced that filling out the Energy InSight app, as well as receiving descriptive and network-based personalized feedback provided them with insight into their CCRF. Although therapists experienced the discussion of network feedback as challenging, it facilitated the case conceptualization. Discussion: Using EMA during waitlist for psychological care seemed feasible. Patients experienced beneficial effects from filling out the EMA app and talking over the personalized feedback reports, which in turn aided case conceptualization and personalized care. Based on this evaluation, an improved version of the Energy InSight app and a therapist training for providing network feedback is developed for implementation in psycho-oncological care.

Prevalence of persistent symptoms after treatment for lyme borreliosis: A prospective observational cohort study.

BACKGROUND: Concerns about long-lasting symptoms attributed to Lyme borreliosis (LB) are widespread in the Western world, while such symptoms are highly prevalent in the general population. METHODS: In the largest prospective study to date, adults with physician-confirmed LB were included at the start of antibiotic treatment. Primary outcomes, prevalence of persistent symptoms and symptom severity, were assessed using three-monthly standardised questionnaires during one year. Persistent symptoms were defined as impaired scores for fatigue (CIS, subscale fatigue), cognitive impairment (CFQ) or pain (SF-36, subscale bodily pain) ≥6 months, with onset <6 months. Outcomes were compared with a longitudinal general population and a tick-bite cohort without LB as a reference. FINDINGS: Of 1135 LB patients (94•8% erythema migrans, 5•2% disseminated LB), 1084 fulfilled primary analysis criteria, as well as 1942 population and 1887 tick-bite controls. Overall prevalence of persistent symptoms in LB patients was 27•2% (95%CI, 24•7%-29•7%); 6•0% and 3•9% higher than in population (21•2%, 95%CI, 19•3%-23•1%; p < 0•0001) and tick-bite (23•3%, 95%CI 21•3%-25•3%; p = 0•016) cohorts, respectively. At 12 months, fatigue, cognitive impairment, and pain were significantly more severe in erythema migrans patients than in reference cohorts, while in disseminated LB patients, only pain was more severe. INTERPRETATION: In treated LB patients, persistent symptoms were significantly more prevalent and symptoms were more severe than in individuals without LB, although the background prevalence was substantial. This suggests an association, either direct or indirect, between persistent symptoms and LB in a relatively small subset of patients. FUNDING: ZonMw; Dutch Ministry of Health, Welfare and Sport.

Scoring of Hypersomnolence and Fatigue in Patients With Obstructive Sleep Apnea Treated With a Titratable Custom-Made Mandibular Advancement Device.

STUDY OBJECTIVES: The objective of this study was to measure fatigue and hypersomnolence in patients with obstructive sleep apnea (OSA) treated with a mandibular advancement device (MAD), using Epworth Sleepiness Scale (ESS) for hypersomnolence and Checklist Individual Strength questionnaire (CIS20R) for fatigue. METHODS: This was a single-center, prospective cohort study. A total of 58 patients with OSA filled out ESS and CIS20R questionnaires at baseline and after 3 months of MAD treatment. A total of 39 full datasets were collected. Statistical analysis for reliability of the questionnaires, comparison between baseline and 3-month follow-up, correlation between the changes in the values of the two questionnaires, and changes in apnea-hypopnea index (AHI) were performed. RESULTS: CIS20R showed excellent reliability in this patient group at baseline and 3-month follow-up (Cronbach α = .97), ESS showed a marginally good reliability (Cronbach α = .82). The CIS20R (82/140) expressed high levels of fatigue at baseline, and ESS showed a normal level of daytime sleepiness. AHI, ESS, and CIS20R were significantly reduced under MAD treatment. A significant correlation between ESS and CIS20R was observed. No significant correlation between any of the questionnaires and the change in AHI was found. CONCLUSIONS: The CIS20R questionnaire results showed a high level of fatigue in the patients with OSA, and the questionnaire can be used to evaluate changes in fatigue due to MAD treatment after 3 months. The ESS failed to show similar characteristics. Therefore, a combination of ESS for hypersomnolence with CIS20R for fatigue is proposed for the follow-up of patients with OSA treated with MAD.

The assessment of fatigue: Psychometric qualities and norms for the Checklist individual strength.

OBJECTIVE: The Checklist Individual Strength (CIS) measures four dimensions of fatigue: Fatigue severity, concentration problems, reduced motivation and activity. On the fatigue severity subscale, a cut-off score of 35 is used. This study 1) investigated the psychometric qualities of the CIS; 2) validated the cut-off score for severe fatigue and 3) provided norms. METHODS: Representatives of the Dutch general population (n=2288) completed the CIS. The factor structure was investigated using an exploratory factor analysis. Internal consistency and test-retest reliability were determined. Concurrent validity was assessed in two additional samples by correlating the CIS with other fatigue scales (Chalder Fatigue Questionnaire, MOS Short form-36 Vitality subscale, EORTC QLQ-C30 fatigue subscale). To validate the fatigue severity cut-off score, a Receiver Operating Characteristics analysis was performed with patients referred to a chronic fatigue treatment centre (n=5243) and a healthy group (n=1906). Norm scores for CIS subscales were calculated for the general population, patients with chronic fatigue syndrome (CFS; n=1407) and eight groups with other medical conditions (n=1411). RESULTS: The original four-factor structure of the CIS was replicated. Internal consistency (α=0.84-0.95) and test-retest reliability (r=0.74-0.86) of the subscales were high. Correlations with other fatigue scales were moderate to high. The 35 points cut-off score for severe fatigue is appropriate, but, given the 17% false positive rate, should be adjusted to 40 for research in CFS. CONCLUSION: The CIS is a valid and reliable tool for the assessment of fatigue, with a validated cut-off score for severe fatigue that can be used in clinical practice.

Associations of sedentary time and patterns of sedentary time accumulation with health-related quality of life in colorectal cancer survivors.

Sedentary behavior (sitting/lying at low energy expenditure while awake) is emerging as an important risk factor that may compromise the health-related quality of life (HRQoL) of colorectal cancer (CRC) survivors. We examined associations of sedentary time with HRQoL in CRC survivors, 2-10 years post-diagnosis. In a cross-sectional study, stage I-III CRC survivors (n = 145) diagnosed (2002-2010) at Maastricht University Medical Center+, the Netherlands, wore the thigh-mounted MOX activity monitor 24 h/day for seven consecutive days. HRQoL outcomes were assessed by validated questionnaires (EORTC QLQ-C30, WHODAS II, Checklist Individual Strength, and Hospital Anxiety and Depression Scale). Confounder-adjusted linear regression models were used to estimate associations with HRQoL outcomes of MOX-derived total and prolonged sedentary time (in prolonged sedentary bouts ≥ 30 min), and usual sedentary bout duration, corrected for waking wear time. On average, participants spent 10.2 h/day sedentary (SD, 1.6), and 4.5 h/day in prolonged sedentary time (2.3). Mean usual sedentary bout duration was 27.3 min (SD, 16.8). Greater total and prolonged sedentary time, and longer usual sedentary bout duration were associated with significantly (P < 0.05) lower physical functioning, and higher disability and fatigue scores. Greater prolonged sedentary time and longer usual sedentary bout duration also showed significant associations with lower global quality of life and role functioning. Associations with distress and social functioning were non-significant. Sedentary time was cross-sectionally associated with poorer HRQoL outcomes in CRC survivors. Prospective studies are needed to investigate whether sedentary time reduction is a potential target for lifestyle interventions aiming to improve the HRQoL of CRC survivors.

Humoral and cellular immune responses after influenza vaccination in patients with postcancer fatigue.

The aim of this study was to compare humoral and cellular immune responses to influenza vaccination in cancer survivors with and without severe symptoms of fatigue. Severely fatigued (n = 15) and non-fatigued (n = 12) disease-free cancer survivors were vaccinated against seasonal influenza. Humoral immunity was evaluated at baseline and post-vaccination by a hemagglutination inhibition assay. Cellular immunity was evaluated at baseline and post-vaccination by lymphocyte proliferation and activation assays. Regulatory T cells were measured at baseline by flow cytometry and heat-shock protein 90 alpha levels by ELISA. Comparable humoral immune responses were observed in fatigued and non-fatigued patients, both pre- and post-vaccination. At baseline, fatigued patients showed a significantly diminished cellular proliferation upon virus stimulation with strain H3N2 (1414 ± 1201 counts), and a trend in a similar direction with strain H1N1 (3025 ± 2339 counts), compared to non-fatigued patients (3099 ± 2401 and 5877 ± 4604 counts, respectively). The percentage of regulatory T lymphocytes was significantly increased (4.4 ± 2.1% versus 2.4 ± 0.8%) and significantly lower amounts of interleukin 2 were detected prior to vaccination in fatigued compared to non-fatigued patients (36.3 ± 44.3 pg/ml vs. 94.0 ± 45.4 pg/ml with strain H3N2 and 28.4 ± 44.0 pg/ml versus 74.5 ± 56.1 pg/ml with strain H1N1). Pre-vaccination heat-shock protein 90 alpha concentrations, post-vaccination cellular proliferation, and post-vaccination cytokine concentrations did not differ between both groups. In conclusion, influenza vaccination is favorable for severely fatigued cancer survivors and should be recommended when indicated. However, compared to non-fatigued cancer survivors, fatigued cancer survivors showed several significant differences in immunological reactivity at baseline, which warrants further investigation.