ObjectivesThe severity of fatigue in RA has improved very little in recent decades, leaving a large unmet need. Fortunately, not all RA patients suffer from persistent fatigue, but the subgroup of... Show moreObjectivesThe severity of fatigue in RA has improved very little in recent decades, leaving a large unmet need. Fortunately, not all RA patients suffer from persistent fatigue, but the subgroup of patients who suffer the most is insufficiently recognizable at diagnosis. As disease activity is partly coupled to fatigue, DAS components may associate with the course of fatigue. We aimed to identify those RA patients who remain fatigued by studying DAS components at diagnosis in relation to the course of fatigue over a 5-year follow-up period in two independent early RA cohorts.MethodsIn all, 1560 consecutive RA patients included in the Leiden Early Arthritis Cohort and 415 RA patients included in the tREACH trial were studied. Swollen joint count, tender joint count, ESR and Patient Global Assessment (PGA) [on a Visual Analogue Scale (VAS)] were studied in relation to fatigue (VAS, 0–100 mm) over a period of 5 years, using linear mixed models.ResultsHigher tender joint count and higher PGA at diagnosis were associated with a more severe course of fatigue. Furthermore, patients with mono- or oligo-arthritis at diagnosis remained more fatigued. The swollen joint count, in contrast, showed an inverse association. An investigation of combinations of the aforementioned characteristics revealed that patients presenting with mono- or oligo-arthritis and PGA ≥ 50 remained the most fatigued over time (+20 mm vs polyarthritis with PGA < 50), while the DAS course over time did not differ. This subgroup comprised 14% of the early RA population. Data from the tREACH trial showed similar findings.ConclusionThe RA patients who remain the most fatigued were those characterized by mono- or oligo-arthritis and high PGA (VAS ≥ 50) at diagnosis. This understanding may enable early-intervention with non-pharmacological approaches in dedicated patient groups. Show less
Quach, K.T.; Dirven, L.; Vingerhoed, A.M.; Bresser, J. de; Dammers, R.; Bos, E.M.; ... ; Furth, W.R. van 2023
Background Fatigue is a commonly reported and severe symptom in primary brain tumor patients, but the exact occurrence in meningioma patients is unknown. This study aimed to determine the frequency... Show moreBackground Fatigue is a commonly reported and severe symptom in primary brain tumor patients, but the exact occurrence in meningioma patients is unknown. This study aimed to determine the frequency and severity of fatigue in meningioma patients as well as associations between the level of fatigue and patient-, tumor-, and treatment-related factors. Methods In this multicenter cross-sectional study, meningioma patients completed questionnaires on fatigue (MFI-20), sleep (PSQI), anxiety and depression (HADS), tumor-related symptoms (MDASI-BT), and cognitive functioning (MOS-CFS). Multivariable regression models were used to evaluate the independent association between fatigue and each patient-, tumor-, and treatment-related factor separately, corrected for relevant confounders. Results Based on predetermined in- and exclusion criteria, 275 patients, on average 5.3 (SD = 2.0) year since diagnosis, were recruited. Most patients had undergone resection (92%). Meningioma patients reported higher scores on all fatigue subscales compared to normative data and 26% were classified as fatigued. Having experienced a complication due to resection (OR 3.6, 95% CI: 1.8-7.0), having received radiotherapy (OR 2.4, 95% CI: 1.2-4.8), a higher number of comorbidities (OR 1.6, 95% CI: 1.3-1.9) and lower educational level (low level as reference; high level OR 0.3, 95% CI: 0.2-0.7) were independently associated with more fatigue. Conclusions Fatigue is a frequent problem in meningioma patients even many years after treatment. Both patient- and treatment-related factors were determinants of fatigue, with the treatment-related factors being the most likely target for intervention in this patient population. Show less
Hiele, K. van der; Egmond, E.E.A. van; Gorp, D.A.M. van; Jongen, P.J.; Reneman, M.F.; Klink, J.J.L. van der; ... ; Visser, L.H. 2022
Previous research discovered a protective effect of higher conscientiousness against a 3-year deterioration in employment status in persons with multiple sclerosis (pwMS). To replicate these... Show morePrevious research discovered a protective effect of higher conscientiousness against a 3-year deterioration in employment status in persons with multiple sclerosis (pwMS). To replicate these findings, we used data from a multicentre prospective cohort study where 145 employed pwMS completed questionnaires, neurological and neuropsychological examinations at baseline and after 3 years. A 3-year deterioration in employment status was reported in 31.0%. We observed no differences in personality, demographics or clinical characteristics between pwMS with deteriorated or stable employment status. These null findings may be partly explained by the classification of deteriorated employment status, which does not reflect Dutch labour conditions. Show less
Marfan syndrome (MFS) is a connective tissue disorder affecting the cardiovascular, ocular, and skeletal system, which may be accompanied by psychological features. This study aimed to determine... Show moreMarfan syndrome (MFS) is a connective tissue disorder affecting the cardiovascular, ocular, and skeletal system, which may be accompanied by psychological features. This study aimed to determine the prevalence of fatigue, anxiety, and symptoms of depression in MFS patients, and to assess the degree to which sociodemographic and clinical variables are associated with fatigue and psychological aspects. The prevalence of fatigue, anxiety, and symptoms of depression were assessed in two cohorts of MFS patients and compared with healthy controls. The checklist individual strength (CIS), and hospital anxiety and depression scale (HADS) questionnaires were utilized. Medical status was assessed (family history of MFS, aortic root dilatation >40 mm, previous aortic surgery, aortic dissection, chronic pain, skeletal involvement, and scoliosis). Severe fatigue was experienced by 37% of the total MFS cohort (n = 155). MFS patients scored significantly higher on the CIS questionnaire, concerning severe fatigue, as compared with the general Dutch population (p < 0.0001). There were no differences in HADS anxiety or depression scores. In older MFS patients, with a more severe cardiovascular phenotype, chronic pain, and a higher unemployment rate, significantly more symptoms of depression were observed, when compared with the general population (p = 0.027) or compared with younger MFS patients (p = 0.026). Multivariate analysis, showed that anxiety was associated with chronic pain (p = 0.022) and symptoms of depression with unemployment (p = 0.024). MFS patients report significantly more severe fatigue as compared with the general population. Since the cause of fatigue is unclear, more research may be needed. Psychological intervention, for example, cognitive behavioral therapy, may contribute to a reduction in psychological symptoms. Show less
Background: While patients with diffuse low-grade glioma (LGG) often survive for years, there is a risk of tumor progression which may impact patients' long-term health-related quality of life ... Show moreBackground: While patients with diffuse low-grade glioma (LGG) often survive for years, there is a risk of tumor progression which may impact patients' long-term health-related quality of life (HRQOL) and neurocognitive functioning (NCF). We present a follow-up of LGG patients and their informal caregivers (T3) who took part in our previous HRQOL investigations (T1, M = 7 and T2 M = 13 years after diagnosis). Methods: Participants completed HRQOL (short form-36 health survey [SF-36]; EORTC-BN20), fatigue (Checklist Individual Strength [CIS]), and depression (Center for Epidemiological Studies-Depression [CES-D]) questionnaires and underwent NCF assessments. T3 scores were compared with matched controls. Changes over time (T1-T2-T3) on group and participant level were assessed. Where available, histology of the initial tumor was revised and immunohistochemical staining for IDH1 R132H mutant protein was performed. Results: Thirty patients and nineteen caregivers participated. Of N = 11 with tissue available, 3 patients had confirmed diffuse LGG. At T3, patients (M = 26 years after diagnosis) had HRQOL and NCF similar to, or better than controls, yet 23.3% and 53.3% scored above the cut-off for depression (>= 16 CES-D) and fatigue (>= 35 CIS), respectively. Caregivers' HRQOL was similar to controls but reported high rates of fatigue (63.2%). Over time, patients' mental health improved (P < .05). Minimal detectable change in HRQOL over time was observed in individual patients (30% improvement; 23.3% decline; 20% both improvement and decline) with 23.3% remaining stable. NCF remained stable or improved in 82.8% of patients. Conclusions: While HRQOL and NCF do not appear greatly impacted during long-term survivorship in LGG, depressive symptoms and fatigue are persistent. Show less
BackgroundWhile patients with diffuse low-grade glioma (LGG) often survive for years, there is a risk of tumor progression which may impact patients’ long-term health-related quality of life (HRQOL... Show moreBackgroundWhile patients with diffuse low-grade glioma (LGG) often survive for years, there is a risk of tumor progression which may impact patients’ long-term health-related quality of life (HRQOL) and neurocognitive functioning (NCF). We present a follow-up of LGG patients and their informal caregivers (T3) who took part in our previous HRQOL investigations (T1, M = 7 and T2 M = 13 years after diagnosis).MethodsParticipants completed HRQOL (short form-36 health survey [SF-36]; EORTC-BN20), fatigue (Checklist Individual Strength [CIS]), and depression (Center for Epidemiological Studies-Depression [CES-D]) questionnaires and underwent NCF assessments. T3 scores were compared with matched controls. Changes over time (T1–T2–T3) on group and participant level were assessed. Where available, histology of the initial tumor was revised and immunohistochemical staining for IDH1 R132H mutant protein was performed.ResultsThirty patients and nineteen caregivers participated. Of N = 11 with tissue available, 3 patients had confirmed diffuse LGG. At T3, patients (M = 26 years after diagnosis) had HRQOL and NCF similar to, or better than controls, yet 23.3% and 53.3% scored above the cut-off for depression (≥16 CES-D) and fatigue (≥35 CIS), respectively. Caregivers’ HRQOL was similar to controls but reported high rates of fatigue (63.2%). Over time, patients’ mental health improved (P < .05). Minimal detectable change in HRQOL over time was observed in individual patients (30% improvement; 23.3% decline; 20% both improvement and decline) with 23.3% remaining stable. NCF remained stable or improved in 82.8% of patients.ConclusionsWhile HRQOL and NCF do not appear greatly impacted during long-term survivorship in LGG, depressive symptoms and fatigue are persistent. Show less
Penson, A.; Walraven, I.; Bronkhorst, E.; Maurice-Stam, H.; Grootenhuis, M.A.; Heiden-van der Loo, M. van der; ... ; Loonen, J. 2022
Simple Summary Survivors of childhood cancer have an increased risk to experience symptoms of severe and persistent fatigue. We studied how fatigue might affect the health-related quality of life... Show moreSimple Summary Survivors of childhood cancer have an increased risk to experience symptoms of severe and persistent fatigue. We studied how fatigue might affect the health-related quality of life of these survivors. Questionnaire items asking about a broad range of daily life aspects were compared between fatigued survivors, survivors without fatigue and the general Dutch population. A total of eleven aspects were studied which were all negatively affected by fatigue, with the largest impact seen for Vitality (how much energy does a person have), General Health (perception of current and future health) and Role Limitations (work-related activities). Results show the negative impact fatigue can have on the daily lives of survivors and why it is important to treat fatigue adequately. Background: Early detection and management of late effects of treatment and their impact on health-related quality of life (HRQOL) has become a key goal of childhood cancer survivorship care. One of the most prevalent late effects is chronic fatigue (CF). The current study aimed to investigate the association between CF and HRQOL in a nationwide cohort of CCS. Methods: Participants were included from the Dutch Childhood Cancer Survivor Study (DCCSS) LATER cohort, a nationwide cohort of CCS. Participants completed the Checklist Individual Strength (CIS) to indicate CF (CIS fatigue severity subscale >= 35 and duration of symptoms >= 6 months) and the Short Form-36 (SF-36) and TNO (Netherlands Organization for Applied Scientific Research) and AZL (Leiden University Medical Centre) Adult's Health-Related Quality of Life questionnaire (TAAQOL) as measures for HRQOL. Differences in mean HRQOL domain scores between CF and non-CF participants were investigated using independent samples t-tests and ANCOVA to adjust for age and sex. The association between CF and impaired HRQOL (scoring >= 2 SD below the population norm) was investigated using logistic regression analyses, adjusting for confounders. Results: A total of 1695 participants were included in the study. Mean HRQOL domain scores were significantly lower in participants with CF. In addition, CF was associated with impaired HRQOL on all of the domains (except physical functioning) with adjusted odds ratios ranging from 2.1 (95% CI 1.3-3.4; sexuality domain) to 30.4 (95% CI 16.4-56.2; vitality domain). Conclusions: CF is associated with impaired HRQOL, urging for the screening and regular monitoring of fatigue, and developing possible preventative programs and interventions. Show less
Egmond, E.E.A. van; Gorp, D.A.M. van; Jongen, P.J.; Klink, J.J.L. van der; Reneman, M.F.; Arnoldus, E.P.J.; ... ; Hiele, K. van der 2021
Purpose This study aimed to identify mental health, physical health, demographic and disease characteristics relating to work productivity in people with multiple sclerosis (MS). Methods In this... Show morePurpose This study aimed to identify mental health, physical health, demographic and disease characteristics relating to work productivity in people with multiple sclerosis (MS). Methods In this cross-sectional study, 236 employed people with MS (median age = 42 years, 78.8% female) underwent neurological and neuropsychological assessments. Additionally, they completed questionnaires inquiring about work productivity (presenteeism: reduced productivity while working, and absenteeism: loss of productivity due to absence from work), mental and physical health, demographic and disease characteristics. Multiple linear and logistic regression analyses were performed with presenteeism and absenteeism as dependent variables, respectively. Results A model with mental and physical health factors significantly predicted presenteeism F(11,202) = 11.33, p < 0.001, R-2 = 0.38; a higher cognitive (p < 0.001) and physical impact (p = 0.042) of fatigue were associated with more presenteeism. A model with only mental health factors significantly predicted absenteeism; chi(2)(11)=37.72, p < 0.001, with R-2 = 0.27 (Nagelkerke) and R-2 = 0.16 (Cox and Snell). Specifically, we observed that more symptoms of depression (p = 0.041) and a higher cognitive impact of fatigue (p = 0.011) were significantly associated with more absenteeism. Conclusions In people with MS, both cognitive and physical impact of fatigue are positively related to presenteeism, while symptoms of depression and cognitive impact of fatigue are positively related to absenteeism. Show less
Monahan, R.C.; Beaart-van de Voorde, L.J.J.; Eikenboom, J.; Fronczek, R.; Kloppenburg, M.; Middelkoop, H.A.M.; ... ; Steup-Beekman, G.M. 2021
IntroductionWe aimed to investigate risk factors for fatigue in patients with systemic lupus erythematosus (SLE) and neuropsychiatric symptoms in order to identify potential interventional... Show moreIntroductionWe aimed to investigate risk factors for fatigue in patients with systemic lupus erythematosus (SLE) and neuropsychiatric symptoms in order to identify potential interventional strategies.MethodsPatients visiting the neuropsychiatric SLE (NPSLE) clinic of the Leiden University Medical Center between 2007-2019 were included. In a multidisciplinary consensus meeting, SLE patients were classified as having neuropsychiatric symptoms of inflammatory origin (inflammatory phenotype) or other origin (non-inflammatory phenotype). Fatigue was assessed with the SF-36 vitality domain (VT) since 2007 and the multidimensional fatigue inventory (MFI) and visual analogue scale (VAS) since 2011. Patients with a score on the SF-36 VT >= 1 standard deviation (SD) away from the mean of age-related controls of the general population were classified as fatigued; patients >= 2 SD away were classified as extremely fatigued. Disease activity was measured using the SLE disease activity index-2000. The influence of the presence of an inflammatory phenotype, disease activity and symptoms of depression and anxiety as measured by the hospital anxiety and depression scale (HADS) was analyzed using multiple regression analyses corrected for age, sex and education.Results348 out of 371 eligible patients filled in questionnaires and were included in this study . The majority was female (87%) and the mean age was 43 +/- 14 years. 72 patients (21%) had neuropsychiatric symptoms of an inflammatory origin. Fatigue was present in 78% of all patients and extreme fatigue was present in 50% of patients with an inflammatory phenotype vs 46% in the non-inflammatory phenotype. Fatigue was similar in patients with an inflammatory phenotype compared to patients with a non-inflammatory phenotype on the SF-36 VT (beta: 0.8 (95% CI -4.8; 6.1) and there was less fatigue in patients with an inflammatory phenotype on the MFI and VAS (beta: -3.7 (95% CI: -6.9; -0.5) and beta: -1.0 (95% CI -1.6; -0.3)). There was no association between disease activity and fatigue, but symptoms of anxiety and depression (HADS) associated strongly with all fatigue measurements.ConclusionThis study suggests that intervention strategies to target fatigue in (NP)SLE patients may need to focus on symptoms of anxiety and depression rather than immunosuppressive treatment. Show less
Cancer-related fatigue has been related to circadian disruptions and lower levels of sleep quality. However, it is unknown whether the circadian phase, which is associated with chronotype and... Show moreCancer-related fatigue has been related to circadian disruptions and lower levels of sleep quality. However, it is unknown whether the circadian phase, which is associated with chronotype and timing of sleep, is related to fatigue after cancer. The aims of this study were to investigate the associations between (1) chronotype and cancer-related fatigue and (2) sleep quality and cancer-related fatigue. In this cross-sectional questionnaire study, 458 (non-)Hodgkin lymphoma survivors (n = 231 female, mean age 49.7 years) completed a Visual Analogue Scale for fatigue (VAS-fatigue) from 0 (no fatigue) to 10 (worst imaginable fatigue), the Munich Chronotype Questionnaire (MCTQ), and the Pittsburgh Sleep Quality Index (PSQI) between October 2018 and July 2019. A hierarchical linear regression analysis was used to evaluate the associations between the dependent variable fatigue and chronotype (based on early, intermediate, or late average midsleep) in Model 1, and fatigue and sleep quality in Model 2. The results showed no indications for an association between chronotype and fatigue (all p values >= 0.50). There were associations between two (out of seven) aspects of sleep quality and fatigue: subjective sleep quality (p < 0.001) and daily dysfunctioning (p < 0.001). Therefore, it is more likely that fatigue is associated with self-reported sleep quality rather than with chronotype. However, experimental studies with objective, physiological data on circadian phase and sleep quality are necessary to confirm the conclusions of this cross-sectional study. Show less
Background: Surgical skills and decision making are influenced by alertness, reaction time, eye-hand coordination, and concentration. Night shift might impair these functions but it is unclear to... Show moreBackground: Surgical skills and decision making are influenced by alertness, reaction time, eye-hand coordination, and concentration. Night shift might impair these functions but it is unclear to what extent. The aim of this study was to investigate whether a night shift routinely impairs the surgeon's fitness to perform and whether this reaches a critical limit as compared to relevant frames of reference.Methods: Consultants (n = 59) and residents (n = 103) conducted fitness to perform measurements at precall, postcall, and noncall moments. This validated self-test consists of an adaptive tracker that is able to objectively measure alertness, reaction time, concentration, and eye-hand coordination, and multiple visual analog scales to subjectively score alertness. Results are compared to sociolegal (ethanol) and professional (operative skills) frames of reference that refer to a decrease under the influence of 0.06% ethanol.Results: Residents spent 1.7 call hours asleep on average as compared to 5.4 for consultants. Subjective alertness decreased in residents after night shifts (-13, P < 0.001) but not in consultants (-1.2, P = NS). The overnight difference in tracker score was -1.17 (P < 0.001) for residents and 0.46 (P = NS) for surgeons. Postcall subjective alertness only correlated to objective alertness in consultants. For residents, hours slept on-call correlated to objective alertness. For consultants, subsequent night calls significantly correlated to objective alertness, with the third subsequent call related to performance below the reference.Conclusions: Consultants remain fit to perform after night call, but subsequent calls may compromise clinical activities. This study provides insight and awareness of individual performance with clear frames of reference. Show less
Placebo and nocebo effects are, respectively, the helpful and harmful treatment effects that do not arise from active treatment components. These effects have thus far been researched most often in... Show morePlacebo and nocebo effects are, respectively, the helpful and harmful treatment effects that do not arise from active treatment components. These effects have thus far been researched most often in pain. It is not yet clear to what extent these findings from pain can be generalized to other somatic symptoms. This review investigates placebo and nocebo effects in four other highly prevalent symptoms: dyspnea, fatigue, nausea, and itch. The role of learning mechanisms (verbal suggestions, conditioning) in placebo and nocebo effects on various outcomes (self-reported, behavioral, and physiological) of these different somatic symptoms is explored. A search of experimental studies indicated that, as in pain, the combination of verbal suggestion and conditioning is generally more effective than suggestion alone for evoking placebo and nocebo effects. However, conditioning appears more and verbal suggestions less relevant in symptoms other than pain, with the exception of placebo effects on fatigue and nocebo effects on itch. Physiological measures, such as heart rate, lung function, or gastric activity, are rarely affected even when self-reported symptoms are. Neurobiological correlates are rarely investigated, and few commonalities appear across symptoms. Expectations generally predict placebo and nocebo effects for dyspnea and itch but seem less involved in fatigue and nausea. Individual characteristics do not consistently predict placebo or nocebo effects across symptoms or studies. In sum, many conclusions deriving from placebo and nocebo pain studies do appear to apply to other somatic symptoms, but a number of important differences exist. Understanding what type of learning mechanisms for which symptom are most likely to trigger placebo and nocebo effects is crucial for generalizing knowledge for research and therapies across symptoms and can help clinicians to optimize placebo effects in practice. Show less
