Lower hair cortisol concentration in adolescent and young adult patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Q-Fever Fatigue Syndrome compared to controls.

BACKGROUND: In patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), momentary cortisol concentrations in blood, urine, and saliva are lower compared to healthy controls. Long-term cortisol concentration can be assessed through hair, but it is unclear whether these concentrations are also lower. Additionally, it is unknown if lower cortisol extends to other patients suffering from persistent fatigue and how hair cortisol concentration (HCC) relates to fatigue levels. Therefore, this study examines HCC in fatigued patients with ME/CFS, Q fever Fatigue Syndrome (QFS), Post-COVID-19 condition (PCC), and Juvenile Idiopathic Arthritis (JIA). METHODS: Adolescent and young adult patients with ME/CFS (n=12), QFS (n=20), PCC (n=8), JIA (n=19), and controls (n=57) were included. Patients participated in a randomized cross-over trial (RCT) targeting fatigue through lifestyle and dietary self-management strategies. HCC was measured pre-post RCT in patients and once in controls, quantified using a LC-MS/MS-based method. Fatigue severity was measured with the Checklist Individual Strength-8. HCC was compared between groups with ANOVAs. Relations between HCC, fatigue severity, and other variables were investigated using linear regression analyses. RESULTS: The ME/CFS (p=.009) and QFS (p=.047) groups had lower HCC compared to controls. Overall, HCC was negatively associated with the presence of symptoms related to chronic fatigue syndromes (e.g., sleeping issues, often feeling tired, trouble thinking clearly; ß=-0.018, p=.035), except in the QFS group (ß=.063, p<.001). Baseline HCC did not predict fatigue improvement during the RCT (p=.449), and HCC increased during the trial (Mdif=.076, p=.021) regardless of clinically relevant fatigue improvement (p=.658). CONCLUSION: Lower cortisol concentration can also be observed in the long-term. Lower HCC is not limited to ME/CFS, as it was also observed in QFS. The role of cortisol may differ between these diagnoses and appears to be unrelated to fatigue levels.

Individual outcomes after tailored versus generic self-management strategies for persistent fatigue in youth with a fatigue syndrome or rheumatic condition: A multiple single-case study.

OBJECTIVE: To examine individual outcomes after tailored lifestyle (PROfeel) or generic dietary advice as self-management intervention for persistent fatigue in adolescents and young adults with a chronic condition, to compare participants who did and did not benefit and to explore changes to factors in the biopsychosocial model of fatigue after PROfeel. METHOD: A multiple single-case AB-phase design was embedded in a randomized crossover trial (N = 45). Intensive longitudinal data (ILD) on outcomes 'fatigue severity', 'self-efficacy' and 'quality of life' (QoL) were collected through weekly smartphone measurement for 20 weeks. ILD on biopsychosocial factors were collected through experience sampling methodology for 28 days pre-post first intervention. Baseline characteristics were compared with t-tests and chi-square tests. Permutation distancing tests were used to assess change over time in all ILD. RESULTS: Regarding weekly measurements, nineteen participants (42.22%) showed small to large positive outcomes (drange = .05 to 2.59), mostly after PROfeel. Eleven participants (24.44%) showed small to moderate negative outcomes (drange = -.02 to -2.46), mostly after dietary advice. Fatigue severity improved most, followed by self-efficacy. Participants who benefitted showed higher QoL levels and lower fatigue and pain levels compared with others at baseline (all p < .02). When positive outcomes were observed after PROfeel, typically ≥1 biopsychosocial factor had been targeted successfully. CONCLUSION: Self-management advice has more potential when tailored to individual characteristics, including the biopsychosocial model of fatigue. PROfeel appears particularly useful as fatigue intervention for individuals with relatively less severe symptoms.

Longitudinal development of fatigue after treatment for childhood cancer: a national cohort study.

BACKGROUND: Fatigue is a distressing and prevalent long-term sequela of treatment for childhood cancer, and there is a need for longitudinal studies to investigate the development of fatigue over time. The objective of this study was to calculate growth-curves for the longitudinal development of fatigue after treatment for childhood cancer, and to investigate the effects of biopsychosocial predictors. MATERIALS AND METHODS: Participants were recruited from a patient monitoring program and data extracted from medical records. Parent-proxy and self-report versions of PedsQLTM Multidimensional Fatigue Scale were used to repeatedly assess fatigue up to 5 years after the end of treatment for childhood cancer. Fatigue was assessed 2440 times for 761 participants (median:3) with proxy-reports (age 2-8 years) and 2657 times for 990 participants with self-reports (above 8 years) (median:2). Mixed models were used to establish growth-curves and to analyze the effect of predictors separately for participants with solid tumors (ST), hemato-oncological malignancies and central nervous system-tumors (CNS). RESULTS: CNS-tumors were associated with more cognitive fatigue than ST at the end of treatment, for both proxy-reports (-11.30, p<.001) and self-reports (-6.78, p=.002), and for proxy-reports of general fatigue (-6.78, p=.002). The only significant difference in change over time was for self-reports of sleep-rest fatigue. The raw scores for the CNS-group decreased with -0.87 per year (95% CI -1.64; -0.81, p=.031) compared to the ST-group. Parental distress was overall the variable most associated with increased fatigue, while immunotherapy was the most frequent medical predictor. National centralization of childhood cancer care decreased fatigue for the CNS-group, but not for other diagnoses. DISCUSSION: Children and adolescents treated for CNS-tumors reported more fatigue than other participants after the end of treatment, and this difference remained over time. Results from this study may help to facilitate the early recognition of children with insufficient recovery of fatigue symptoms.

Fatigue mediates the relationship between emotional and cognitive functioning in children post-cancer treatment.

BACKGROUND/OBJECTIVES: Children treated for cancer are at risk to develop cognitive problems. Insight in underlying associations with emotional functioning and fatigue can be used to optimize interventions. We therefore aim to study emotional functioning, fatigue, and cognitive functioning in children postcancer treatment and investigate whether fatigue mediates the relationship between emotional and cognitive functioning. DESIGN/METHODS: Emotional functioning, fatigue, and cognitive functioning were assessed in children post-cancer treatment using subscales of the Pediatric Quality of Life Inventory (PedsQL) Generic Core Scales, Multidimensional Fatigue Scale and Cognitive Functioning Scale. A one sample t-test was used to compare outcomes with general population peers and mediation analysis was used to address the effect of fatigue on the relationship between emotional and cognitive functioning. RESULTS: A total of 137 children (mean age: 13.6, SD ± 3.3 years; mean time since end of treatment: 7.1 months, SD ± 5.9) participated. Lower scores on emotional functioning (Cohen's d [D]: 0.4), fatigue (D: 0.8) and cognitive functioning (D: 0.6) were found (p < .001) in children post-cancer treatment than in peers. A medium association was found between emotional and cognitive functioning (standardized regression coefficient [ß]: 0.27, p < .001), which was mediated by fatigue (ß = 0.16). CONCLUSIONS: Outcomes on emotional and cognitive functioning are decreased and fatigue is increased in children postcancer treatment. Fatigue mediates the relationship between emotional and cognitive functioning. Our results show the importance to focus on fatigue amongst stress as a target for intervention to improve cognitive functioning.

The RISE study protocol: resilience impacted by positive stressful events for people with cystic fibrosis.

Introduction: For people with cystic fibrosis (CF), gaining access to elexacaftor/tezacaftor/ivacaftor (ETI) therapy, a new modulator drug combination, is perceived as a positive life event. ETI leads to a strong improvement of disease symptoms. However, some people with CF experience a deterioration in mental wellbeing after starting ETI therapy. The primary objective of this study is to investigate if and in which direction mental wellbeing of people with CF changes after starting ETI therapy. Our secondary objectives include, among others, investigation of underlying biological and psychosocial factors associated with a change in mental wellbeing of people with CF after starting ETI therapy. Methods and analysis: The Resilience lmpacted by Positive Stressful Events (RISE) study is a single-arm, observational, prospective longitudinal cohort. It has a timeframe of 60 weeks: 12 weeks before, 12 weeks after, 24 weeks after and 48 weeks after the start of ETI therapy. The primary outcome is mental well-being, measured at each of these four time points. Patients aged ≥12 years at the University Medical Center Utrecht qualifying for ETI therapy based on their CF mutation are eligible. Data will be analysed using a covariance pattern model with a general variance covariance matrix. Ethics: The RISE study was classified by the institutional review board as exempt from the Medical Research Involving Human Subjects Act. Informed consent was obtained by both the children (12-16 years) and their caregivers, or only provided by the participants themselves when aged ≥16 years.

Self-reported quantity and quality of sleep in children and adolescents with a chronic condition compared to healthy controls.

To assess self-reported quantity and quality of sleep in Dutch children with a chronic condition compared to healthy controls and to the recommended hours of sleep for youth. Sleep quantity and quality were analyzed in children with a chronic condition (cystic fibrosis, chronic kidney disease, congenital heart disease, (auto-)immune disease, and medically unexplained symptoms (MUS); n = 291; 15 ± 3.1 years, 63% female. A subset of 171 children with a chronic condition were matched to healthy controls using Propensity Score matching, based on age and sex, ratio 1:4. Self-reported sleep quantity and quality were assessed with established questionnaires. Children with MUS were analyzed separately to distinguish between chronic conditions with and without an identified pathophysiological cause. Generally, children with a chronic condition met the recommended amount of sleep, however 22% reported poor sleep quality. No significant differences in sleep quantity and quality were found between the diagnosis groups. Children with a chronic condition and with MUS slept significantly more than healthy controls at ages 13, 15, and 16. Both at primary and secondary school, poor sleep quality was least frequent reported in children with a chronic condition and most often reported in children with MUS.  Conclusion: Overall, children with chronic conditions, including MUS, met the recommended hours of sleep for youth, and slept more than healthy controls. However, it is important to obtain a better understanding of why a substantial subset of children with chronic conditions, mostly children with MUS, still perceived their sleep quality as poor. What is Known: • According to the Consensus statement of the American Academy of Sleep medicine, typically developing children (6 to 12 years) should sleep 9 to 12 h per night, and adolescents (13 to 18 years) should sleep 8 to 10 h per night. • Literature on the optimal quantity and quality of sleep in children with a chronic condition is very limited. What is New: Our findings are important and provide novel insights: • In general, children with a chronic condition sleep according to the recommended hours of sleep. • A substantial subset of children with chronic conditions, perceived their sleep quality as poor. Although this was reported mostly by children with medically unexplained symptoms (MUS), the found poor sleep quality was independent of specific diagnosis.

Internet-delivered cognitive behavioural therapy for chronic fatigue among adolescents with a chronic medical condition: a single case study.

BACKGROUND: Severe fatigue is a prominent symptom among adolescents with a chronic medical condition, with major impact on their well-being and daily functioning. Internet-based cognitive behavioural therapy (I-CBT) is a promising treatment for severe fatigue among adolescents with a chronic medical condition, but its effectiveness has not been studied. AIMS: We developed an I-CBT intervention for disabling fatigue in a chronic medical condition and tested its feasibility and effectiveness in an adolescent with an immune dysregulation disorder (IDD), namely juvenile idiopathic arthritis (JIA). METHOD: The application of I-CBT is illustrated through a clinical case study of a 15-year-old girl with JIA and chronic severe fatigue. An A-B single case experimental design was used with randomization of the waiting period prior to start of the intervention. Outcomes were weekly measures of fatigue severity, physical functioning, school absence and pain severity. RESULTS: Fatigue severity significantly decreased following I-CBT. Improvements were observed towards increased school attendance and improved physical functioning following the intervention, but these effects were too small to become significant. CONCLUSIONS: The study provides preliminary support for the feasibility and effectiveness of the application of I-CBT for severe fatigue in adolescents with a long-term medical condition.

Identifying disrupted biological factors and patient-tailored interventions for chronic fatigue in adolescents and young adults with Q-Fever Fatigue Syndrome, Chronic Fatigue Syndrome and Juvenile Idiopathic Arthritis (QFS-study): study protocol for a randomized controlled trial with single-subject experimental case series design.

BACKGROUND: Chronic fatigue with a debilitating effect on daily life is a frequently reported symptom among adolescents and young adults with a history of Q-fever infection (QFS). Persisting fatigue after infection may have a biological origin with psychological and social factors contributing to the disease phenotype. This is consistent with the biopsychosocial framework, which considers fatigue to be the result of a complex interaction between biological, psychological, and social factors. In line, similar manifestations of chronic fatigue are observed in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and juvenile idiopathic arthritis (JIA). Cognitive behavioral therapy is often recommended as treatment for chronic fatigue, considering its effectiveness on the group level. However, not everybody benefits on the individual level. More treatment success at the individual level might be achieved with patient-tailored treatments that incorporate the biopsychosocial framework. METHODS: In addition to biological assessments of blood, stool, saliva, and hair, the QFS-study consists of a randomized controlled trial (RCT) in which a single-subject experimental case series (N=1) design will be implemented using Experience Sampling Methodology in fatigued adolescents and young adults with QFS, CFS/ME, and JIA (aged 12-29). With the RCT design, the effectiveness of patient-tailored PROfeel lifestyle advices will be compared against generic dietary advices in reducing fatigue severity at the group level. Pre-post analyses will be conducted to determine relevance of intervention order. By means of the N=1 design, effectiveness of both advices will be measured at the individual level. DISCUSSION: The QFS-study is a comprehensive study exploring disrupted biological factors and patient-tailored lifestyle advices as intervention in adolescent and young adults with QFS and similar manifestations of chronic fatigue. Practical or operational issues are expected during the study, but can be overcome through innovative study design, statistical approaches, and recruitment strategies. Ultimately, the study aims to contribute to biological research and (personalized) treatment in QFS and similar manifestations of chronic fatigue. TRIAL REGISTRATION: Trial NL8789 . Registered July 21, 2020.

The PROactive cohort study: rationale, design, and study procedures.

Children with a chronic condition face more obstacles than their healthy peers, which may impact their physical, social-emotional, and cognitive development. The PROactive cohort study identifies children with a chronic disease at high risk of debilitating fatigue, decreased daily life participation and psychosocial problems, as well as children who are resilient and thrive despite the challenges of growing up with a chronic condition. Both groups will teach us how we can best support children, adolescents and parents to adapt to and manage a disease, as well as tailor interventions to their specific needs.This cohort follows a continuous longitudinal design. It is based at the Wilhelmina Children's Hospital (WKZ) in the Netherlands and has been running since December 2016. Children with a chronic condition (e.g. cystic fibrosis, juvenile idiopathic arthritis, chronic kidney disease, or congenital heart disease) as well children with medically unexplained fatigue or pain in a broad age range (2-18 years) are included, as well as their parent(s). Data are collected from parents (of children between 2 and 18 years) and children (8-18 years), as well as data from their electronic health record (EHR). Primary outcome measures are fatigue, daily life participation, and psychosocial well-being, all assessed via patient- and proxy-reported outcome measures. Generic biological/lifestyle, psychological, and social factors were assessed using clinical assessment tools and questionnaires. In the PROactive cohort study the research assessment is an integrated part of clinical care. Children are included when they visit the outpatient clinic and are followed up annually.

Physiological predictors of cardiorespiratory fitness in children and adolescents with cystic fibrosis without ventilatory limitation.

OBJECTIVES: [1] To investigate the cardiorespiratory fitness (CRF) levels in children and adolescents with cystic fibrosis (CF) with no ventilatory limitation (ventilatory reserve ⩾ 15%) during exercise, and [2] to assess which physiological factors are related to CRF. METHODS: A cross-sectional study design was used in 8- to 18-year-old children and adolescents with CF. Cardiopulmonary exercise testing was used to determine peak oxygen uptake normalized to body weight as a measure of CRF. Patients were defined as having 'low CRF' when CRF was less than 82%predicted. Physiological predictors used in this study were body mass index z-score, P. Aeruginosa lung infection, impaired glucose tolerance (IGT) including CF-related diabetes, CF-related liver disease, sweat chloride concentration, and self-reported physical activity. Backward likelihood ratio (LR) logistic regression analysis was used. RESULTS: Sixty children and adolescents (51.7% boys) with a median age of 15.3 years (25th-75th percentile: 12.9-17.0 years) and a mean percentage predicted forced expiratory volume in 1 second of 88.5% (±16.9) participated. Mean percentage predicted CRF (ppVO2peak/kg) was 81.4% (±12.4, range: 51%-105%). Thirty-three patients (55.0%) were classified as having 'low CRF'. The final model that best predicted low CRF included IGT (p = 0.085; Exp(B) = 6.770) and P. Aeruginosa lung infection (p = 0.095; Exp(B) = 3.945). This model was able to explain between 26.7% and 35.6% of variance. CONCLUSIONS: CRF is reduced in over half of children and adolescents with CF with normal ventilatory reserve. Glucose intolerance and P. Aeruginosa lung infection seem to be associated to low CRF in children and adolescents with CF.

Parent-Child Dyadic Coping and Quality of Life in Chronically Diseased Children.

Different forms of dyadic coping are associated with positive outcomes in partner relationships, yet little is known about dyadic coping in parent-child relationships. The current research explored the association between parent-child dyadic coping and children's quality of life in 12-18-year old children with a chronic disease (i.e., cystic fibrosis, autoimmune diseases, and children post-cancer treatment). In a sample of 105 parent-child dyads, self-reported forms of dyadic coping (i.e., stress communication, problem-oriented, emotion-oriented, and negative dyadic coping) and children's quality of life were assessed. Children reported more stress communication and negative dyadic coping than their parents, while parents reported more problem-oriented dyadic coping and emotion-oriented dyadic coping than their children. More stress communication of the child was associated with more emotion-oriented dyadic coping and less negative dyadic coping of the parent. More negative dyadic coping of the child was associated with less stress communication, problem-oriented dyadic coping and emotion-oriented dyadic coping of the parent. Additionally, both children's and parents' negative dyadic coping were associated with lower self-reported pediatric quality of life and parents' emotion-oriented dyadic coping was associated with higher pediatric quality of life. These findings emphasize that children and their parents mutually influence each other and that dyadic coping is associated with children's quality of life. Theoretical and practical implications are discussed.

Effectiveness of Internet-Based Cognitive Behavior Therapy (Fatigue in Teenagers on the Internet) for Adolescents With Chronic Fatigue Syndrome in Routine Clinical Care: Observational Study.

BACKGROUND: Internet-based cognitive behavior therapy (I-CBT) for adolescents with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) has been shown to be effective in a randomized controlled trial (RCT; Fatigue in Teenagers on the Internet [FITNET]). FITNET can cause a significant reduction in fatigue and disability. OBJECTIVE: We aimed to investigate whether FITNET treatment implemented in routine clinical care (IMP-FITNET) was as effective, using the outcomes of the FITNET RCT as the benchmark. METHODS: Outcomes of CFS/ME adolescents who started IMP-FITNET between October 2012 and March 2018 as part of routine clinical care were compared to the outcomes in the FITNET RCT. The primary outcome was fatigue severity assessed posttreatment. The secondary outcomes were self-reported physical functioning, school attendance, and recovery rates. Clinically relevant deterioration was assessed posttreatment, and for this outcome, a face-to-face CBT trial was used as the benchmark. The attitude of therapists toward the usability of IMP-FITNET was assessed through semistructured interviews. The number of face-to-face consultations during IMP-FITNET was registered. RESULTS: Of the 384 referred adolescents with CFS/ME, 244 (63.5%) started IMP-FITNET, 84 (21.9%) started face-to-face CBT, and 56 (14.6%) were not eligible for CBT. Posttreatment scores for fatigue severity (mean 26.0, SD 13.8), physical functioning (mean 88.2, SD 15.0), and full school attendance (mean 84.3, SD 26.5) fell within the 95% CIs of the FITNET RCT. Deterioration of fatigue and physical functioning after IMP-FITNET was observed at rates of 1.2% (n=3) and 4.1% (n=10), respectively, which is comparable to a waiting list condition (fatigue: 1.2% vs 5.7%, χ21=3.5, P=.06; physical functioning: 4.1% vs 11.4%, χ21=3.3, P=.07). Moreover, 41 (16.8%) IMP-FITNET patients made use of face-to-face consultations. CONCLUSIONS: IMP-FITNET is an effective and safe treatment for adolescents with CFS/ME in routine clinical care.

Role of parents in fatigue of children with a chronic disease: a cross-sectional study.

Objective: As parents majorly impact their child's well-being, and as fatigue is a highly prevalent threat to the well-being of children with a chronic disease, we aimed to explore the association between parental factors and fatigue in children with a chronic disease. Design: Cross-sectional study. Setting: Two Dutch children's hospitals. Population: Children 2-18 years of age with either an autoimmune disease, cystic fibrosis or post-cancer treatment, and one of their parents. Main outcome measures: Paediatric fatigue was measured using the PedsQL Multidimensional Fatigue Scale. Parental factors included parental pain, fatigue and physical symptoms, parental distress, catastrophising thoughts about their child's pain and family empowerment. Multiple linear regressions were used to study associations with paediatric fatigue. A multivariable regression model was used to assess the effect of the different parental factors on paediatric fatigue. All analyses were adjusted for the age and sex of the child. Results: 204 families participated (mean age 11.0±4.3 and 43.5±6.3 years for children and parents, respectively; 69% participation rate). More parental pain, fatigue and physical symptoms, and more parental distress and pain catastrophising were associated with more paediatric fatigue. More parental empowerment was associated with less paediatric fatigue on both subscales. In the multivariable model, only paediatric age remained significantly associated with fatigue. In a separate multivariable model for children 8-18 years old, more parental distress (ß=-1.9, 95% CI -3.7 to -0.1) was also significantly associated with more paediatric fatigue. Conclusions: In a population of children with a chronic disease, parental factors, both physical and psychosocial, were associated with paediatric fatigue. Our study provides evidence that more family empowerment is associated with less paediatric fatigue. This exploratory study adds to our knowledge of associated factors with fatigue in paediatric chronic disease, providing starting points for targeted interventions.

Daily life participation in childhood chronic disease: a qualitative study on the child's and parent's perspective.

Objective: To understand how a child with a stable chronic disease and his/her parents shape his/her daily life participation, we assessed: (1) the parents' goals regarding the child's daily life participation, (2) parental strategies regarding the child's participation and () how children and their parents interrelate when their goals regarding participation are not aligned. Methods: This was a qualitative study design using a general inductive approach. Families of children 8-19 years with a stable chronic disease (cystic fibrosis, autoimmune disease or postcancer treatment) were recruited from the PROactive study. Simultaneous in-depth interviews were conducted separately with the child and parent(s). Analyses included constant comparison, coding and categorisation. Results: Thirty-one of the 57 invited families (54%) participated. We found that parents predominantly focus on securing their child's well-being, using participation as a means to achieve well-being. Moreover, parents used different strategies to either support participation consistent with the child's healthy peers or support participation with a focus on physical well-being. The degree of friction between parents and their child was based on the level of agreement on who takes the lead regarding the child's participation. Conclusions: Interestingly, parents described participation as primarily a means to achieve the child's well-being, whereas children described participation as more of a goal in itself. Understanding the child's and parent's perspective can help children, parents and healthcare professionals start a dialogue on participation and establish mutual goals. This may help parents and children find ways to interrelate while allowing the child to develop his/her autonomy.

Internet and smartphone-based ecological momentary assessment and personalized advice (PROfeel) in adolescents with chronic conditions: A feasibility study.

OBJECTIVE: Growing up with a chronic disease comes with challenges, such as coping with fatigue. Many adolescents are severely fatigued, though its associated factors exhibit considerable interpersonal and longitudinal variation. We assessed whether PROfeel, a combination of a smartphone-based ecological momentary assessment (EMA) method using the internet, followed by a face-to-face dialogue and personalized advice for improvement of symptoms or tailor treatment based on a dynamic network analysis report, was feasible and useful. STUDY DESIGN: Feasibility study in fatigued outpatient adolescents 12-18 years of age with cystic fibrosis, autoimmune disease, post-cancer treatment, or with medically unexplained fatigue. Participants were assessed at baseline to personalize EMA questions. EMA was conducted via smartphone notifications five times per day for approximately six weeks. Hereby, data was collected via the internet. The EMA results were translated into a personalized report, discussed with the participant, and subsequently translated into a personalized advice. Afterwards, semi-structured interviews on feasibility and usefulness were held. RESULTS: Fifty-seven adolescents were assessed (mean age 16.2 y ± 1.6, 16% male). Adolescents deemed the smartphone-based EMA feasible, with the app being used for an average of 49 days. Forty-two percent of the notifications were answered and 85% of the participants would recommend the app to other adolescents. The personalized report was deemed useful and comprehensible and 95% recognized themselves in the personalized report, with 64% rating improved insight in their symptoms and subsequent steps towards an approach to reduce one's fatigue as good or very good. CONCLUSIONS: PROfeel was found to be highly feasible and useful for fatigued adolescents with a chronic condition. This innovative method has clinical relevance through bringing a patient's daily life into the clinical conversation.

Fatigue among children with a chronic disease: a cross-sectional study.

Objective: To determine: (1) which biological/lifestyle, psychological and/or social factors are associated with fatigue among children with a chronic disease and (2) how much each of these factors contributes to explaining variance in fatigue. Design and setting: This was a cross-sectional study across two children's hospitals. Patients: We included children aged 8-18 years who visited the outpatient clinic with cystic fibrosis, an autoimmune disease or postcancer treatment. Main outcome measures: Fatigue was assessed using the PedsQL Multidimensional Fatigue Scale. Generic biological/lifestyle, psychological and social factors were assessed using clinical assessment tools and questionnaires. Multiple linear regression analyses were used to test the associations between these factors and fatigue. Finally, a multivariable regression model was used to determine which factor(s) have the strongest effect on fatigue. Results: A total of 434 out of 902 children were included (48% participation rate), with a median age of 14.5 years; 42% were male. Among these 434 children, 21.8% were severely fatigued. Together, all biopsychosocial factors explained 74.6% of the variance in fatigue. More fatigue was uniquely associated with poorer physical functioning, more depressive symptoms, more pressure at school, poorer social functioning and older age. Conclusions: Fatigue among children with a chronic disease is multidimensional. Multiple generic biological/lifestyle, psychological and social factors were strongly associated with fatigue, explaining 58.4%; 65.8% and 50.0% of the variance in fatigue, respectively. Altogether, almost three-quarters of the variance in fatigue was explained by this biopsychosocial model. Thus, when assessing and treating fatigue, a transdiagnostic approach is preferred, taking into account biological, psychological and social factors.

Recruiting Adolescents With Chronic Fatigue Syndrome/Myalgic Encephalomyelitis to Internet-Delivered Therapy: Internal Pilot Within a Randomized Controlled Trial.

BACKGROUND: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) in adolescents is common and disabling. Teenagers in the United Kingdom are more likely to recover if they access specialist care, but most do not have access to a local specialist CFS/ME service. Delivering treatment remotely via the internet could improve access to treatment. OBJECTIVE: This study aims to assess (1) the feasibility of recruitment and retention into a trial of internet-delivered specialist treatment for adolescents with CFS/ME and (2) the acceptability of trial processes and 2 web-based treatments (to inform continuation to full trial). METHODS: This study is an internal pilot for the initial 12 months of a full randomized controlled trial (RCT), with integrated qualitative methods (analysis of recruitment consultations and participant and clinician interviews). Recruitment and treatment were delivered remotely from a specialist pediatric CFS/ME treatment service within a hospital in South West United Kingdom. Adolescents (aged 11-17 years) from across the United Kingdom with a diagnosis of CFS/ME and no access to local specialist treatment were referred by their general practitioner to the treatment center. Eligibility assessment and recruitment were conducted via remote methods (telephone and on the web), and participants were randomized (via a computer-automated system) to 1 of 2 web-based treatments. The trial intervention was Fatigue in Teenagers on the InterNET in the National Health Service, a web-based modular CFS/ME-specific cognitive behavioral therapy program (designed to be used by young people and their parents or caregivers) supported by individualized clinical psychologist electronic consultations (regular, scheduled therapeutic message exchanges between participants and therapist within the platform). The comparator was Skype-delivered activity management with a CFS/ME clinician (mainly a physiotherapist or occupational therapist). Both treatments were intended to last for up to 6 months. The primary outcomes were (1) the number of participants recruited (per out-of-area referrals received between November 1, 2016, to October 31, 2017) and the proportion providing 6-month outcome data (web-based self-report questionnaire assessing functioning) and (2) the qualitative outcomes indicating the acceptability of trial processes and treatments. RESULTS: A total of 89 out of 150 (59.3% of potentially eligible referrals) young people and their parents or caregivers were recruited, with 75 out of 89 (84.2%) providing 6-month outcome data. Overall, web-based treatment was acceptable; however, participants and clinicians described both the advantages and disadvantages of remote methods. No serious adverse events were reported. CONCLUSIONS: Recruiting young people (and their parents or caregivers) into an RCT of web-based treatment via remote methods is feasible and acceptable. Delivering specialist treatment at home via the internet is feasible and acceptable, although some families prefer to travel across the United Kingdom for face-to-face treatment. TRIAL REGISTRATION: ISRCTN 18020851; http://www.isrctn.com/ISRCTN18020851. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13063-018-2500-3.

Daily life participation in childhood chronic disease: a qualitative study.

OBJECTIVE: Opportunities to participate in daily life have improved considerably for children with chronic disease. Nevertheless, they still face challenges associated with their ever-present illness affecting every aspect of their lives. To best help these children, we aimed to assess the child's own perspective on participation and the main considerations that affect participation in a stable phase of disease. METHODS: Qualitative study design was applied. Semistructured, indepth interviews were conducted and analysed by a general inductive approach using constant comparison, coding and categorisation. Children 8-18 years old with a chronic disease were recruited from a cohort study involving cystic fibrosis, autoimmune disease and post-treatment paediatric cancer. RESULTS: 31 of the 56 (55%) invited patients participated. From the perspective of children with chronic disease, participation is considered more than merely engaging in activities; rather, they view having a sense of belonging, the ability to affect social interactions and the capacity to keep up with peers as key elements of full participation. Some children typically placed a higher priority on participation, whereas other children typically placed a higher priority on their current and/or future needs, both weighing the costs and benefits of their choices and using disclosure as a strategy. CONCLUSIONS: Enabling full participation from the child's perspective will help realise patient-centred care, ultimately helping children self-manage their participation. Caregivers can stimulate this participation by evaluating with children how to achieve a sense of belonging, active involvement and a role within a peer group. This requires active collaboration between children, healthcare providers and caregivers.

Investigating the effectiveness and cost-effectiveness of FITNET-NHS (Fatigue In Teenagers on the interNET in the NHS) compared to activity management to treat paediatric chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME): amendment to the published protocol.

The FITNET-NHS Trial is a UK, national, trial investigating whether an online cognitive behavioural therapy program (FITNET-NHS) for treating chronic fatigue syndrome/ME in adolescents is clinically effective and cost-effective in the NHS. At the time of writing (September 2019), the trial was recruiting participants. This article presents an update to the planned sample size and data collection duration previously published within the trial protocol. TRIAL REGISTRATION: ISRCTN, ID: 18020851. Registered 8 April 2016.

Fatigue in childhood chronic disease.

BACKGROUND AND OBJECTIVES: Recently, in adults, the incidence and severity of fatigue was found to exist rather independently from the somatic diagnosis. Since fatigue is distressing when growing up with a chronic disease, we aim to investigate: (1) the prevalence and extent of fatigue among various paediatric chronic diseases and (2) the effect of fatigue on health-related quality of life (HRQoL). DESIGN AND SETTING: Cross-sectional study in two children's hospitals. PATIENTS: Children and adolescents 2-18 years of age with cystic fibrosis, an autoimmune disease or postcancer treatment visiting the outpatient clinic. OUTCOME MEASURES: Fatigue and HRQoL were assessed using the Pediatric Quality of Life Inventory (PedsQL) multidimensional fatigue scale (with lower scores indicating more fatigue) and PedsQL generic core scales, respectively. Linear regression analysis and analysis of covariance were used to compare fatigue scores across disease groups and against two control groups. The effect of fatigue on HRQoL was calculated. Data were adjusted for age, sex and reporting method. RESULTS: 481 children and adolescents were assessed (60% participation rate, mean age 10.7±4.9, 42% men). Children and adolescents with chronic disease reported more fatigue than the general population (mean difference -6.6, 95% CI -8.9 to -4.3 (range 0-100)), with a prevalence of severe fatigue of 21.2%. Fatigue scores did not differ significantly between disease groups on any fatigue domain. Fatigue was associated with lower HRQoL on all domains. CONCLUSIONS: Fatigue in childhood chronic disease is a common symptom that presents across disease, age and sex groups. Fatigue affects HRQoL. Our findings underscore the need to systematically assess fatigue. Future studies should determine possible biological and psychosocial treatment targets.