Chronic Fatigue Syndrome/myalgic Encephalopathy Research Articles

Metabolic analysis of amino acids and vitamin B6 pathways in lymphoma survivors with cancer related chronic fatigue.

Chronic cancer-related fatigue (CF) is a common and distressing condition in a subset of cancer survivors and common also after successful treatment of malignant lymphoma. The etiology and pathogenesis of CF is unknown, and lack of biomarkers hampers development of diagnostic tests and successful therapy. Recent studies on the changes of amino acid levels and other metabolites in patients with chronic fatigue syndrome/myalgic encephalopathy (CFS/ME) have pointed to possible central defects in energy metabolism. Here we report a comprehensive analysis of serum concentrations of amino acids, including metabolites of tryptophan, the kynurenine pathway and vitamin B6 in a well characterized national Norwegian cohort of lymphoma survivors after high-dose therapy and autologous stem cell transplantation. Among the 20 standard amino acids in humans, only tryptophan levels were significantly lower in both males and females with CF compared to non-fatigued survivors, a strikingly different pattern than seen in CFS/ME. Markers of tryptophan degradation by the kynurenine pathway (kynurenine/tryptophan ratio) and activation of vitamin B6 catabolism (pyridoxic acid/(pyridoxal + pyridoxal 5'-phosphate), PAr index) differed in survivors with or without CF and correlated with known markers of immune activation and inflammation, such as neopterin, C-reactive protein and Interleukin-6. Among personal traits and clinical findings assessed simultaneously in participating survivors, higher neuroticism score, obesity and higher PAr index were significantly associated with increased risk of CF. Collectively, these data point to low grade immune activation and inflammation as a basis for CF in lymphoma survivors.

Development of a conceptual framework to underpin a health-related quality of life outcome measure in paediatric chronic fatigue syndrome/myalgic encephalopathy (CFS/ME): prioritisation through card ranking

PurposeChronic fatigue syndrome (CFS)/myalgic encephalopathy (ME) is relatively common in children and is disabling at an important time in their development. This study aimed to develop a conceptual framework of paediatric CFS/ME using the patient-perspective to ensure that the content of a new outcome measure includes the outcomes most important to young people.MethodsWe developed a child-centred interactive card ranking exercise that included health-related quality of life (HRQoL) outcomes identified from a previous review of the literature as well as qualitative work. Adolescents and their parents selected and ranked the outcomes most important to them and discussed each outcome in further detail. Adolescents were purposively sampled from a single specialist paediatric CFS/ME service in England. Interviews were audio recorded and transcribed verbatim, and thematic framework analysis was used to develop the final conceptual framework.ResultsWe interviewed 43 participants in which there are 21 adolescents, 12–17 years of age with mild–moderate CFS/ME and their parents (20 mothers and 2 fathers). ‘Symptoms’, ‘tiredness’, ‘payback and crashing’ and ‘activities and hobbies’ were ranked most important to improve by both children and parents. Children ranked ‘school’ higher than parents and parents ranked ‘mood’ higher than children. A youth- specific CFS/ME conceptual framework of HRQoL was produced that included 4 outcome domains and 11 subdomains: sleep, tiredness, problems concentrating, individual symptoms, fluctuation and payback, daily and general activities, participation in school, leisure and social life, mood, anxiety and self-esteem.ConclusionsAn interactive card ranking exercise worked well for adolescents aged 12–17 to elicit the most important outcomes to them and explore each domain in further detail. We developed a final conceptual framework of HRQoL that forms the basis of a new paediatric patient-reported outcome measure (PROM) in CFS/ME.

Developing and pretesting a new patient reported outcome measure for paediatric Chronic Fatigue Syndrome/ Myalgic Encephalopathy (CFS/ME): cognitive interviews with children

BackgroundThere is a lack of patient derived, child specific outcome measures to capture what health outcomes are important to children with Chronic Fatigue Syndrome/ Myalgic Encephalopathy (CFS/ME). We developed a new Patient Reported Outcome Measure (PROM) for paediatric CFS/ME through qualitative research with children. This study aimed to pre-test the new measure through cognitive interviews with children with CFS/ME.MethodsCognitive interviews were undertaken in children’s homes or over Skype. The Three-Step Test-Interview (TSTI) method was used to assess the quality of the draft PROM with children with CFS/ME to identify problems with initial content and design and test modifications over subsequent interview rounds. Children were purposively sampled from a single specialist paediatric CFS/ME service in England.ResultsTwenty-four children and their parents took part. They felt the new measure captured issues relevant to their condition and preferred it to the generic measures they completed in clinical assessment. Changes were made to item content and phrasing, timeframe and response options and tested through three rounds of interviews.ConclusionsCognitive interviews identified problems with the draft PROM, enabling us to make changes and then confirm acceptability in children aged 11–18. Further cognitive interviews are required with children 8–10 years old to examine the acceptability and content validity and provide evidence for age related cut offs of the new PROM to meet FDA standards. This study demonstrates the content validity of the new measure as relevant and acceptable for children with CFS/ME. The next stage is to undertake a psychometric evaluation to support the reduction of items, confirm the structure of the PROM and provide evidence of the data quality, reliability and validity.

A 4-Day Mindfulness-Based Cognitive Behavioral Intervention Program for CFS/ME. An Open Study, With 1-Year Follow-Up.

Background: Chronic Fatigue Syndrome/Myalgic Encephalopathy (CFS/ME) is an incapacitating illness in which single treatment interventions seem to have variable effects. Based on an earlier study we have conducted a new study with a concentrated intervention program. The aims of this study were to: (1) explore the clinical course for patients with CFS/ME who participated in a treatment program delivered during four consecutive days, and (2) evaluate their satisfaction with this program.Methods: 305 patients diagnosed with CFS/ME (Oxford criteria), recruited from a clinical population referred to a specialist outpatient clinic, participated in an open uncontrolled study of the clinical course through 1 year. The study group participated in a 4-day group intervention program, comprised by education, cognitive group therapy sessions, mindfulness sessions, physical activity and writing sessions, within a context of cognitive behavioral therapy, mindfulness, acceptance and commitment model.Assessments were done by self-reports prior to the first consultation, 1 week before and 1 week after the intervention program, and at 3 months and 1 year after the intervention. SPSS 23 and R 3.3 were used for statistical analyses. The associations between case definitions and the outcome measures (Chalder Fatigue Scale (FS), Short Form 36 (SF-36) physical functioning scale) were assessed by a linear mixed effects model (LME).Results: Results showed statistically significant clinical changes for 80% of the patients after the intervention, changes being sustained through 1 year after the program. For both Fatigue Scale (FS) and the SF-36 there were statistically significant effects of time from baseline to all time points with a statistically significant drop in scores, applying the linear mixed effects model.A subgroup fulfilling the inclusion criteria from the PACE study (Chalder Fatigue Scale >6/11, SF-36 Physical functioning <65/100) showed clinically significant improvement through 1 year, changes in outcome measures were statistically significant (p < 0.001). None of the patients included in the program dropped out, and a great majority of patients expressed high satisfaction with the content, focus and amount of treatment. Conclusion: Clinical changes observed from pre-treatment to 1 year follow-up could represent effects of the 4-day concentrated intervention program, and should be further explored in a controlled study.

Association between cytokines and psychiatric symptoms in chronic fatigue syndrome and healthy controls

Purpose: The reports regarding the status of the immune system in patients with chronic fatigue syndrome/myalgic encephalopathy (CFS/ME) have been inconclusive. We approached this question by comparing a strictly defined group of CFS/ME outpatients to healthy control individuals, and thereafter studied cytokines in subgroups with various psychiatric symptoms.Materials and methods: Twenty patients diagnosed with CFS/ME according to the Fukuda criteria and 20 age- and sex-matched healthy controls were enrolled in the study. Plasma was analysed by ELISA for levels of the cytokines TNF-α, IL-4, IL-6 and IL-10. Participants also answered questionnaires regarding health in general, and psychiatric symptoms in detail.Results: Increased plasma levels of TNF-α in CFS/ME patients almost reached significance compared to healthy controls (p = .056). When studying the CFS/ME and control groups separately, there was a significant correlation between TNF-α and The Hospital Anxiety and Depression Scale (HADS) depressive symptoms in controls only, not in the CFS/ME group. A correlation between IL-10 and psychoticism was found in both groups, whereas the correlation for somatisation was seen only in the CFS/ME group. When looking at the total population, there was a significant correlation between TNF-α and both the HADS depressive symptoms and the SCL-90-R cluster somatisation. Also, there was a significant association between IL-10 and the SCL-90-R cluster somatisation when analyzing the cohort (patients and controls together).Conclusions: These findings indicate that immune activity in CFS/ME patients deviates from that of healthy controls, which implies potential pathogenic mechanisms and possible therapeutic approaches to CFS/ME. More comprehensive studies should be carried out on defined CFS/ME subgroups.

Long-term follow-up of multi-disciplinary outpatient treatment for chronic fatigue syndrome/myalgic encephalopathy

Aims: The current study evaluated the long-term effectiveness of a multi-disciplinary approach to chronic fatigue syndrome/myalgic encephalopathy (CFS/ME) in a UK outpatient service. Methods: A longitudinal questionnaire survey was posted to 300 patients, incorporating measures of fatigue, physical functioning, mental health, and pain. Outcome measures administered at baseline (prior to service use) were compared to assessments at discharge, and at follow-up (average 34 months post-intervention). Results: Linear mixed modelling showed that fatigue, physical functioning, and depression significantly improved, although the improvement was reduced for fatigue, physical functioning, and pain at follow-up. Gainful employment had a significant positive association with most measures. Conclusions: The targeted multi-disciplinary service appeared to be at least somewhat effective long-term, and highly acceptable to patients. Patients appeared to benefit from individual and group approaches that combined cognitive behavioural therapy, graded exercise therapy, and pacing.

Comparison of chronic fatigue syndrome/myalgic encephalopathy with other disorders: an observational study

ObjectivesTo examine the level of activity in online discussion forums for chronic fatigue syndrome/myalgic encephalopathy (CFS/ME) compared to other disorders. We hypothesized the level of activity to be higher in CFS/ME online discussion forums.DesignObservational studySettingNorway, which has more than 80% household coverage in internet access, September 2009ParticipantsTwelve Norwegian disorder-related online discussion forumsMain outcome measuresNumber of registered users and number of posted messages on each discussion forumResultsTwo forums were targeted towards individuals with CFS/ME. These forums had the highest number of registered users per estimated 1,000 cases in the population (50.5 per 1,000 and 29.7 per 1,000), followed by a site for drug dependency (5.4 per 1,000). Counting the number of posted messages per 1,000 cases gave similar indications of high online activity in the CFS/ME discussion forums.ConclusionsCFS/ME online forums had more than ten times the relative activity of any other disorder or condition related forum. This high level of activity may have multiple explanations. Individuals suffering from a stigmatized condition of unknown aetiology may use the internet to look for explanations of symptoms or to seek out alternative treatments. Internet forum activity may also be reinforced by the creation of in-group identity and pre-morbid personality traits. More knowledge on the type and quality of information provided in online forums is urgently needed.

Association between school absence and physical function in paediatric chronic fatigue syndrome/myalgic encephalopathy

Objective:To investigate factors associated with school attendance and physical function in paediatric chronic fatigue syndrome/myalgic encephalopathy (CFS/ME).Design:Cross-sectional study.Setting:Regional specialist CFS/ME service.Patients:Children and young people aged under 18 years.Outcome measures:Self-reported school...

Cognitive behavioural therapy in chronic fatigue syndrome: a randomised controlled trial of an outpatient group programme

To test the hypothesis that group cognitive behavioural therapy (CBT) will produce an effective and cost-effective management strategy for patients in primary care with chronic fatigue syndrome/myalgic encephalopathy (CFS/ME). A double-blind, randomised controlled trial was adopted with three arms. Outcomes were assessed at baseline and 6 and 12 months after first assessment and results were analysed on an intention-to-treat basis. A health psychology department for the management of chronic illness in a general hospital in Bristol, UK. Adults with a diagnosis of CFS/ME referred by their GP. The three interventions were group CBT incorporating graded activity scheduling, education and support group (EAS) and standard medical care (SMC). The primary outcome measure was the Short Form with 36 Items (SF-36) physical and mental health summary scales. Other outcome measures included the Chalder fatigue scale, Hospital Anxiety and Depression Scale, General Health Questionnaire, physical function (shuttles walked, walking speed and perceived fatigue), health utilities index and cognitive function (mood, recall and reaction times). A total of 153 patients were recruited to the trial and 52 were randomised to receive CBT, 50 to EAS and 51 to SMC. Twelve patients failed to attend for the 12-month follow-up and 19 patients attended one follow-up, but not both. The sample was found to be representative of the patient group and the characteristics of the three groups were similar at baseline. Three outcome measures, SF-36 mental health score, Chalder fatigue scale and walking speed, showed statistically significant differences between the groups. Patients in the CBT group had significantly higher mental health scores [difference +4.35, 95% confidence interval (CI) +0.72 to +7.97, p = 0.019], less fatigue (difference -2.61, 95% CI -4.92 to -0.30, p = 0.027) and were able to walk faster (difference +2.83 shuttles, 95% CI +1.12 to +5.53, p = 0.0013) than patients in the SMC group. CBT patients also walked faster and were less fatigued than those randomised to EAS (walking speed: difference +1.77, 95% CI +0.025 to +3.51, p = 0.047; fatigue: difference -3.16, 95% CI -5.59 to -0.74, p = 0.011). Overall, no other statistically significant difference across the groups was found, although for many measures a trend towards an improved outcome with CBT was seen. Except for walking speed, which, on average, increased by +0.87 shuttles (95% CI +0.09 to +1.65, p = 0.029) between the 6- and 12-month follow-ups, the scores were similar at 6 and 12 months. At baseline, 30% of patients had an SF-36 physical score within the normal range and 52% had an SF-36 mental health score in the normal range. At 12 months, the physical score was in the normal range for 46% of the CBT group, 26% of the EAS group and 44% of SMC patients. For mental health score the percentages were CBT 74%, EAS 67% and SMC 70%. Of the CBT group, 32% showed at least a 15% increase in physical function and 64% achieved a similar improvement in their mental health. For the EAS and SMC groups, this improvement in physical and mental health was achieved for 40 and 60% (EAS) and 49 and 53% (SMC), respectively. The cost-effectiveness of the intervention proved very difficult to assess and did not yield reliable conclusions. Group CBT did not achieve the expected change in the primary outcome measure as a significant number did not achieve scores within the normal range post-intervention. The treatment did not return a significant number of subjects to within the normal range on this domain; however, significant improvements were evident in some areas. Group CBT was effective in treating symptoms of fatigue, mood and physical fitness in CFS/ME. It was found to be as effective as trials using individual therapy in these domains. However, it did not bring about improvement in cognitive function or quality of life. There was also evidence of improvement in the EAS group, which indicates that there is limited value in the non-specific effects of therapy. Further research is needed to develop better outcome measures, assessments of the broader costs of the illness and a clearer picture of the characteristics best fitted to this type of intervention.

Chronic fatigue syndrome in young people: the spectrum and the myths

Large telephone surveys in both the UK and USA suggest that chronic fatigue syndrome/myalgic encephalopathy (CFS/ME) in children is both surprisingly common (0.19–2%), and indiscriminate in who it affects (Jordan et al, 2000; Chalder et al, 2003; Jones et al, 2004). There is no gender preference, no social class gradient, and all ethnic groups are affected. The CFS/ME described in studies where patients are recruited from specialist care is much rarer and predominantly affects white females of higher socioeconomic status (Patel et al, 2003).

Chronic fatigue syndrome in young people: the spectrum and the myths

Large telephone surveys in both the UK and USA suggest that chronic fatigue syndrome/myalgic encephalopathy (CFS/ME) in children is both surprisingly common (0.19–2%), and indiscriminate in who it affects (Jordan et al, 2000; Chalder et al, 2003; Jones et al, 2004). There is no gender preference, no social class gradient, and all ethnic groups are affected. The CFS/ME described in studies where patients are recruited from specialist care is much rarer and predominantly affects white females of higher socioeconomic status (Patel et al, 2003).

How fatigue is related to other somatic symptoms

Aims: To assess the relation between fatigue and somatic symptoms in healthy adolescents and adolescents with chronic fatigue syndrome/myalgic encephalopathy (CFS/ME). Methods: Seventy two adolescents with CFS were compared within...

Chronic fatigue syndrome in children

Summary Chronic fatigue syndrome/myalgic encephalopathy (CFS/ME) is a heterogeneous condition that causes significant morbidity in young people. Its cause is unknown with current evidence suggesting that, in mild and moderate cases, cognitive behaviour therapy and/or graded exercise should be the treatment of choice. The majority of adolescents will improve or get better. Further research is required to determine aetiology and optimum management.

Can antibacterials treat chronic fatigue syndrome?

Bacterial and viral infections may underlie the symptoms commonly seen in patients with chronic illnesses such as chronic fatigue syndrome/myalgic encephalopathy (CFS/ME), fibromyalgia syndrome (FMS), Gulf War illness (GWI) and rheumatoid arthritis (RA), and may be amenable to antibacterial and antiviral therapy, according to the results of a presentation at the 2nd Myalgic Encephalopathy/Chronic Fatigue Syndrome conference [Sydney, Australia; February 1999].