2020 – Page 14 – American ME and CFS Society

Health-related Quality of Life in Norwegian Adolescents Living With Chronic Fatigue Syndrome

Abstract:

Purpose: The primary aim was to measure health related quality of life (HRQoL) in a Norwegian cohort of adolescents with Chronic Fatigue Syndrome (CFS/ME). A secondary aim was to identify factors before diagnosis, at time of diagnosis and after diagnosis that were associated with HRQoL.

Methods: In this cross-sectional population-based study, HRQoL was measured by Pediatric Quality of Life Inventory™ Generic Core scale version 4.0 (PedsQL4.0) in 63 adolescents with CFS/ME. In addition, fatigue was measured by PedsQL Multidimensional Fatigue scale (PedsQL-MFS), depressive symptoms were measured by the Short Mood and Feelings Questionnaire (SMFQ), and disruption in school activities was measured by The De Paul Pediatric Health Questionnaire (DPHQ-N). Data were also collected from medical records and patient interviews.

Results: Age at diagnosis was 15 (2) years (mean (SD)), and four out of five participants were female. Time from diagnosis to reply was 39 (22) months. Adolescents with CFS/ME reported PedsQL4.0 score 50 (17), and boys reported a better score than girls (64 vs 47, 95% Confidence Interval (CI) for difference (- 27; – 6)). There were positive associations between overall HRQoL and support from a schoolteacher, school attendance or participation in leisure activities. There were negative associations between overall HRQoL and delayed school progression, having been to rehabilitation stay and depressive symptoms.

Conclusion: HRQoL in adolescents diagnosed with CFS/ME was low. The associations between reported HRQoL, healthcare previously provided, support from a schoolteacher, school attendance and participation in leisure activity may provide information of value when developing refined strategies for healthcare among adolescents with CFS/ME. Possible causal relationships must however be explored in future studies.

Source: Similä WA, Halsteinli V, Helland IB, Suvatne C, Elmi H, Rø TB. Health-related quality of life in Norwegian adolescents living with chronic fatigue syndrome. Health Qual Life Outcomes. 2020;18(1):170. Published 2020 Jun 5. doi:10.1186/s12955-020-01430-z https://hqlo.biomedcentral.com/articles/10.1186/s12955-020-01430-z (Full text)

Paediatric Chronic Fatigue Syndrome Patients’ and Parents’ Perceptions of Recovery

Abstract:

Objectives: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is common in children and adolescents; however, little is known about how we should define recovery. This study aims to explore perceptions of recovery held by paediatric patients with CFS/ME and their parents.

Methods: Children with CFS/ME and their parents were recruited through a single specialist paediatric CFS/ME service. Data were collected through semistructured interviews with children and parents. The interview questions explored how participants would know if they/their child had recovered from CFS/ME. Thematic analysis was used to identify patterns within the data.

Results: Twenty-one children with CFS/ME, twenty mothers and two fathers were interviewed. Some children found it hard to define recovery as the illness had become a ‘new normal’. Others thought recovery would indicate returning to pre-morbid levels of activity or achieving the same activity level as peers (socialising, education and leisure activities). Increased flexibility in routines and the absence of payback after activities were important. The interviews highlighted the concept of recovery as highly individual with wide variation in symptoms experienced, type and level of activity that would signify recovery. Parents describe how changes in mood and motivation would signify their child’s recovery, but children did not reflect on this.

Conclusion: Some parents and children struggle to define what would constitute complete recovery. However, signs of recovery were more easily identifiable. Definitions of recovery went far beyond symptom reduction and were focused towards rebuilding lives.

Source: Harland MR, Parslow RM, Anderson N, Byrne D, Crawley E. Paediatric chronic fatigue syndrome patients’ and parents’ perceptions of recovery. BMJ Paediatr Open. 2019;3(1):e000525. Published 2019 Dec 2. doi:10.1136/bmjpo-2019-000525 https://bmjpaedsopen.bmj.com/content/3/1/e000525 (Full text)

Preliminary ICF Core Set for Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in Rehabilitation Medicine

Abstract:

Objective: To create and evaluate a preliminary ICF Core Set for myalgic encephalomyelitis/chronic fatigue syndrome using a team-based approach.

Design: Observational study.

Subjects/patients: A total of 100 consecutive patients (mean age 45 years, standard deviation (SD) 9 years) were assessed by a rehabilitation team and included in the study.

Methods: A preliminary International Classification of Functioning, Disability and Health (ICF) Core Set was created, based on literature studies, and on discussion forums between the team and the researchers. Patients were assessed by a rehabilitation medicine team regarding impairments in body function, activity limitations, and restrictions in participation.

Results: Clinical assessments of the component Body Functions found impairments in energy, fatigue, physical endurance, fatigability, sleep and pain in 82-100% of patients. At least half of the patients had impairments in higher cognitive functions, attention, and emotions, as well as sound and light hypersensitivity, general hyper-reactivity and thermoregulatory functions. For the component Activity/Participation, the most frequent limitations and restrictions were in doing housework (93%), assisting others (92%), acquisition of goods and services (90%), remunerative employment (87%), handling stressful situations (83%), preparing food (83%), recreation and leisure (82%), informal socializing (78%) and carrying out daily activities (77%). The most frequent degrees of impairments/limitations/restrictions assessed were light and moderate, except for remunerative employment, for which restrictions were severe.

Conclusion: Using unconventional methods, this study sets out a preliminary ICF Core Set list for patients with myalgic encephalomyelitis/chronic fatigue syndrome. Further studies are required to improve and test this Core Set in myalgic encephalomyelitis/chronic fatigue syndrome populations.

Source: Bileviciute-Ljungar I, Schult ML, Borg K, Ekholm J. Preliminary ICF core set for patients with myalgic encephalomyelitis/chronic fatigue syndrome in rehabilitation medicine [published online ahead of print, 2020 May 28]. J Rehabil Med. 2020;10.2340/16501977-2697. doi:10.2340/16501977-2697 https://www.medicaljournals.se/jrm/content/abstract/10.2340/16501977-2697 (Full text)

The concept of ‘illness without disease’ impedes understanding of chronic fatigue syndrome: a response to Sharpe and Greco

Abstract:

In a recent article in Medical Humanities, Sharpe and Greco characterise myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) as an ‘illness without disease’, citing the absence of identified diagnostic markers. They attribute patients’ rejection of psychological and behavioural interventions, such as cognitive–behavioural therapy (CBT) and graded exercise therapy (GET), to a ‘paradox’ resulting from a supposed failure to acknowledge that ‘there is no good objective evidence of bodily disease’. In response, we explain that understandings about the causes of and treatments for medical complaints have shifted across centuries, and that conditions once thought to be ‘psychosomatic’ have later been determined to have physiological causes.

We also note that Sharpe and Greco do not disclose that leading scientists and physicians believe that ME/CFS is a biomedical disease, and that numerous experts, not just patients, have rejected the research underlying the CBT/GET treatment approach. In conclusion, we remind investigators that medical classifications are always subject to revision based on subsequent research, and we therefore call for more humility before declaring categorically that patients are experiencing ‘illness without disease’.

Source: Lubet S, Tuller D. The concept of ‘illness without disease’ impedes understanding of chronic fatigue syndrome: a response to Sharpe and Greco [published online ahead of print, 2020 Jun 1]. Med Humanit. 2020;medhum-2019-011807. doi:10.1136/medhum-2019-011807 https://mh.bmj.com/content/early/2020/06/01/medhum-2019-011807

Systematic Review of the Epidemiological Burden of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Across Europe: Current Evidence and EUROMENE Research Recommendations for Epidemiology

Abstract:

This review aimed at determining the prevalence and incidence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in Europe. We conducted a primary search in Scopus, PubMed and Web of Science for publications between 1994 and 15 June 2019 (PROSPERO: CRD42017078688). Additionally, we performed a backward-(reference lists) and forward-(citations) search of the works included in this review. Grey literature was addressed by contacting all members of the European Network on ME/CFS (EUROMENE). Independent reviewers searched, screened and selected studies, extracted data and evaluated the methodological and reporting quality. For prevalence, two studies in adults and one study in adolescents were included. Prevalence ranged from 0.1% to 2.2%. Two studies also included incidence estimates.

In conclusion, studies on the prevalence and incidence of ME/CFS in Europe were scarce. Our findings point to the pressing need for well-designed and statistically powered epidemiological studies. To overcome the shortcomings of the current state-of-the-art, EUROMENE recommends that future research is better conducted in the community, reviewing the clinical history of potential cases, obtaining additional objective information (when needed) and using adequate ME/CFS case definitions; namely, the Centers for Disease Control & Prevention−1994, Canadian Consensus Criteria, or Institute of Medicine criteria

Source: Estévez-López F, Mudie K, Wang-Steverding X, et al. Systematic Review of the Epidemiological Burden of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Across Europe: Current Evidence and EUROMENE Research Recommendations for Epidemiology. J Clin Med. 2020;9(5):E1557. Published 2020 May 21. doi:10.3390/jcm9051557 (Full article) https://www.mdpi.com/2077-0383/9/5/1557

Mitochondria and Immunity in Chronic Fatigue Syndrome

Abstract:

It is widely accepted that the pathophysiology and treatment of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) could be considerably improved. The heterogeneity of ME/CFS and the confusion over its classification have undoubtedly contributed to this, although this would seem a consequence of the complexity of the array of ME/CFS presentations and high levels of diverse comorbidities.

This article reviews the biological underpinnings of ME/CFS presentations, including the interacting roles of the gut microbiome/permeability, endogenous opioidergic system, immune cell mitochondria, autonomic nervous system, microRNA-155, viral infection/re-awakening and leptin as well as melatonin and the circadian rhythm. This details not only relevant pathophysiological processes and treatment options, but also highlights future research directions.

Due to the complexity of interacting systems in ME/CFS pathophysiology, clarification as to its biological underpinnings is likely to considerably contribute to the understanding and treatment of other complex and poorly managed conditions, including fibromyalgia, depression, migraine, and dementia. The gut and immune cell mitochondria are proposed to be two important hubs that interact with the circadian rhythm in driving ME/CFS pathophysiology.

Source: Anderson G, Maes M. Mitochondria and immunity in chronic fatigue syndrome [published online ahead of print, 2020 May 26]. Prog Neuropsychopharmacol Biol Psychiatry. 2020;109976. doi:10.1016/j.pnpbp.2020.109976 https://pubmed.ncbi.nlm.nih.gov/32470498/

Sleep problems in adolescents with CFS: A case-control study nested within a prospective clinical cohort

Abstract:

Sleep problems have a negative impact on a range of outcomes and are very common in adolescents with chronic fatigue syndrome (CFS). We aimed to (a) establish whether adolescents with CFS have more self-reported sleep problems than illness controls as well as healthy controls, (b) investigate changes in sleep problems and (c) explore the extent to which sleep problems at baseline predict fatigue and functioning at follow-up in adolescents with CFS. The Insomnia Scale was completed by 121 adolescents with CFS, 78 healthy adolescents and 27 adolescents with asthma. Eighty (66%) treatment-naïve adolescents with CFS completed questionnaires approximately 3 months later. Adolescents with CFS reported increased sleep problems compared to healthy controls and adolescents with asthma. In CFS, there was no significant change in sleep problems without treatment over a 3-month follow-up. Sleep problems at baseline predicted a significant proportion of the variance in sleep problems at follow-up. Sleep problems should be targeted in treatment. Regulating the ‘body clock’ via the regulation of sleep could influence outcomes not assessed in this study such as school attainment.

Source: Loades ME, Rimes KA, Chalder T. Sleep problems in adolescents with CFS: A case-control study nested within a prospective clinical cohort [published online ahead of print, 2020 May 22]. Clin Child Psychol Psychiatry. 2020;1359104520918364. doi:10.1177/1359104520918364 https://journals.sagepub.com/doi/abs/10.1177/1359104520918364

Patients’ Experiences and Effects of Non-Pharmacological Treatment for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome – A Scoping Mixed Methods Review

Abstract:

Purpose: The EU COST Action 15111 collaboration on myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) aims to assess current research and identify knowledge gaps in Europe. Presently, our purpose is to map the effects of non-pharmacological therapies (NPTs) for ME/CFS, and what patients find important in the treatment process.

Methods: A scoping mixed methods literature review of European studies identified 16 papers fulfiling our inclusion criteria. The quantitative and qualitative studies were synthesized separately in tables. Additionally, extracts from the qualitative studies were subjected to translational analysis.

Results: Effect studies addressed cognitive behavioural therapy (CBT, n = 4), multimodal rehabilitation (n = 2) and activity-pacing (n = 2). CBT reduced fatigue scores more than usual care or waiting list controls. The effects of rehabilitation and activity-pacing were inconsistent. The contents, assessment methods and effects of rehabilitation and activity pacing studies varied. For patients, health professionals’ recognition of ME/CFS and support were crucial, but they expressed ambiguous experiences of what the NPTs entail.

Conclusions: Methodological differences make comparisons across NPTs impossible, and from a patient perspective the relevance of the specific contents of NPTs are unclear. Future well-designed studies should focus on developing NPTs tailored to patients’ concerns and evaluation tools reflecting what is essential for patients.

Source: Mengshoel AM, Helland IB, Meeus M, Castro-Marrero J, Pheby D, Bolle Strand E. Patients’ experiences and effects of non-pharmacological treatment for myalgic encephalomyelitis/chronic fatigue syndrome – a scoping mixed methods review. Int J Qual Stud Health Well-being. 2020;15(1):1764830. doi:10.1080/17482631.2020.1764830 https://pubmed.ncbi.nlm.nih.gov/32432991/ (Full text)

Heart Rate Thresholds to Limit Activity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients (Pacing): Comparison of Heart Rate Formulae and Measurements of the Heart Rate at the Lactic Acidosis Threshold during Cardiopulmonary Exercise Testing

Abstract:

Introduction: Based on the hypothesis that oxidative metabolism is impaired in ME/CFS, a previous study recommended a pacing self-management strategy to prevent post-exertional malaise. This strategy involved a prescription to maintain a heart rate below the anaerobic threshold during physical activities. In the absence of lactate sampling or a cardiopulmonary exercise test (CPET), the pacing self-management formula defines 55% of the age-specific predicted maximal heart rate as the heart rate at the anaerobic threshold. Thus far there has been no empiric evidence to test this self-pacing method of predicting heart rate at anaerobic threshold. The aim of this study was to compare published formula-derived heart rates at the anaerobic threshold with the actual heart rate at the lactic acidosis threshold as determined by CPET.

Methods and Results: Adults with ME/CFS who had undergone a symptom-limited CPET were eligible for this study (30 males, 60 females). We analysed males and females separately because of sex-based differences in peak oxygen consumption. From a review paper, formulae to calculate maximal predicted heart rate were used for healthy subjects. We compared the actual heart rate at the lactic acid threshold during CPET to the predicted heart rates determined by formulae. Using Bland-Altman plots, calculated bias: the mean difference between the actual CPET heart rate at the anaerobic threshold and the formula predicted heart rate across several formulae varied between -28 and 19 bpm in male ME/CFS patients. Even in formulae with a clinically acceptable bias, the limits of agreement (mean bias ± 2SD) were unacceptably high for all formulae. For female ME/CFS patients, bias varied between 6 and 23 bpm, but the limits of agreement were also unacceptably high for all formulae.

Conclusion: Formulae generated in an attempt to help those with ME/CFS exercise below the anaerobic threshold do not reliably predict actual heart rates at the lactic acidosis threshold as measured by a cardiopulmonary exercise test. Formulae based on age-dependent predicted peak heart rate multiplied by 55% have a wide age-specific variability and therefore have a limited application in clinical practice.

Source: van Campen, C. , Rowe, P. and Visser, F. (2020) Heart Rate Thresholds to Limit Activity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients (Pacing): Comparison of Heart Rate Formulae and Measurements of the Heart Rate at the Lactic Acidosis Threshold during Cardiopulmonary Exercise Testing. Advances in Physical Education, 10, 138-154. doi: 10.4236/ape.2020.102013. https://www.scirp.org/journal/paperinformation.aspx?paperid=100333 (Full text)

Intravenous Cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. An Open-Label Phase II Study

Abstract:

Introduction: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disease with high symptom burden, of unknown etiology, with no established treatment. We observed patients with long-standing ME/CFS who got cancer, and who reported improvement of ME/CFS symptoms after chemotherapy including cyclophosphamide, forming the basis for this prospective trial.

Materials and methods: This open-label phase II trial included 40 patients with ME/CFS diagnosed by Canadian criteria. Treatment consisted of six intravenous infusions of cyclophosphamide, 600-700 mg/m2, given at four-week intervals with follow-up for 18 months, extended to 4 years. Response was defined by self-reported improvements in symptoms by Fatigue score, supported by Short Form 36 (SF-36) scores, physical activity measures and other instruments. Repeated measures of outcome variables were assessed by General linear models. Responses were correlated with specific Human Leukocyte Antigen (HLA) alleles.

Results: The overall response rate by Fatigue score was 55.0% (22 of 40 patients). Fatigue score and other outcome variables showed significant improvements compared to baseline. The SF-36 Physical Function score increased from mean 33.0 at baseline to 51.5 at 18 months (all patients), and from mean 35.0 to 69.5 among responders. Mean steps per 24 h increased from mean 3,199 at baseline to 4,347 at 18 months (all patients), and from 3,622 to 5,589 among responders. At extended follow-up to 4 years 68% (15 of 22 responders) were still in remission. Patients positive for HLA-DQB1*03:03 and/or HLA-C*07:04 (n = 12) had significantly higher response rate compared to patients negative for these alleles (n = 28), 83 vs. 43%, respectively. Nausea and constipation were common grade 1-2 adverse events. There were one suspected unexpected serious adverse reaction (aggravated POTS) and 11 serious adverse events in eight patients.

Conclusion: Intravenous cyclophosphamide treatment was feasible for ME/CFS patients and associated with an acceptable toxicity profile. More than half of the patients responded and with prolonged follow-up, a considerable proportion of patients reported ongoing remission. Without a placebo group, clinical response data must be interpreted with caution. We nevertheless believe a future randomized trial is warranted. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02444091.

Source: Rekeland IG, Fosså A, Lande A, Ktoridou-Valen I, Sørland K, Holsen M, Tronstad KJ, Risa K, Alme K, Viken MK, Lie BA, Dahl O, Mella O, Fluge Ø. Intravenous Cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. An Open-Label Phase II Study. Front Med (Lausanne). 2020 Apr 29;7:162. doi: 10.3389/fmed.2020.00162. eCollection 2020. https://www.frontiersin.org/articles/10.3389/fmed.2020.00162/full (Full text)