2017 – Page 21 – American ME and CFS Society

Long-term economic evaluation of cognitive-behavioural group treatment versus enhanced usual care for functional somatic syndromes

Abstract:

OBJECTIVE: Patients with functional somatic syndromes (FSS) such as fibromyalgia and chronic fatigue syndrome have a poor outcome and can incur high healthcare and societal costs. We aimed to compare the medium-term (16 months) cost-effectiveness and the long-term (40 months) economic outcomes of a bespoke cognitive-behavioural group treatment (STreSS) with that of enhanced usual care (EUC).

METHODS: We obtained complete data on healthcare and indirect costs (i.e. labour marked-related and health-related benefits) from public registries for 120 participants from a randomised controlled trial. Costs were calculated as per capita public expenses in 2010 €. QALYs gained were estimated from the SF-6D. We conducted a medium-term cost-effectiveness analysis and a long-term cost-minimization analysis from both a healthcare (i.e. direct cost) and a societal (i.e. total cost) perspective.

RESULTS: In the medium term, the probability that STreSS was cost-effective at thresholds of 25,000 to 35,000 € per QALY was 93-95% from a healthcare perspective, but only 50-55% from a societal perspective. In the long term, however, STreSS was associated with increasing savings in indirect costs, mainly due to a greater number of patients self-supporting. When combined with stable long-term reductions in healthcare expenditures, there were total cost savings of 7184 € (95% CI 2271 to 12,096, p=0.004) during the third year after treatment.

CONCLUSION: STreSS treatment costs an average of 1545 €. This cost was more than offset by subsequent savings in direct and indirect costs. Implementation could both improve patient outcomes and reduce costs.

Source: Schröder A, Ørnbøl E, Jensen JS, Sharpe M, Fink P. Long-term economic evaluation of cognitive-behavioural group treatment versus enhanced usual care for functional somatic syndromes. J Psychosom Res. 2017 Mar;94:73-81. doi: 10.1016/j.jpsychores.2017.01.005. Epub 2017 Jan 10. https://www.ncbi.nlm.nih.gov/pubmed/28183406

Important factors to consider when treating children with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): perspectives of health professionals from specialist services

Abstract:

BACKGROUND: Paediatric Chronic Fatigue Syndrome (CFS)/Myalgic Encephalomyelitis (ME) is relatively common and disabling. Improving treatment requires the development of Patient Reported Outcome Measures (PROMs) that enable clinicians and researchers to collect patient-centred evidence on outcomes. Health professionals are well placed to provide clinical insight into the condition, its treatment and possible outcomes. This study aimed to understand the perspectives of specialist paediatric CFS/ME health professionals and identify outcomes that are clinically important.

METHODS: Focus groups and interviews were held with 15 health professionals involved in the care of children with CFS/ME from the four largest specialist paediatric CFS/ME services in the NHS in England. A range of clinical disciplines were included and experience in paediatric CFS/ME ranged from 2 months to 25 years. Ten participants (67%) were female. Focus groups and interviews were recorded, transcribed verbatim and data were analysed using thematic analysis.

RESULTS: All health professionals identified the impact of CFS/ME across multiple aspects of health. Health professionals described four areas used to assess the severity of the illness and outcome in children: 1) symptoms; 2) physical function; 3) participation (school, activities and social life); and 4) emotional wellbeing. They also described the complexity of the condition, contextual factors and considerations for treatment to help children to cope with the condition.

CONCLUSIONS: Clinically important outcomes in paediatric CFS/ME involve a range of aspects of health. Health professionals consider increases in physical function yet maintaining school functioning and participation more widely as important outcomes from treatment. The results are similar to those described by children in a recent study and will be combined to develop a new child-specific PROM that has strong clinical utility and patient relevance.

Source: Parslow RM, Shaw A, Haywood KL, Crawley E. Important factors to consider when treating children with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): perspectives of health professionals from specialist services. BMC Pediatr. 2017 Feb 1;17(1):43. doi: 10.1186/s12887-017-0799-7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5286567/ (Full article)

Giardia-specific cellular immune responses in post-giardiasis chronic fatigue syndrome

Abstract:

BACKGROUND: The role of pathogen specific cellular immune responses against the eliciting pathogen in development of post-infectious chronic fatigue syndrome (PI-CFS) is not known and such studies are difficult to perform. The aim of this study was to evaluate specific anti-Giardia cellular immunity in cases that developed CFS after Giardia infection compared to cases that recovered well. Patients reporting chronic fatigue in a questionnaire study three years after a Giardia outbreak were clinically evaluated five years after the outbreak and grouped according to Fukuda criteria for CFS and idiopathic chronic fatigue. Giardia specific immune responses were evaluated in 39 of these patients by proliferation assay, T cell activation and cytokine release analysis. 20 Giardia exposed non-fatigued individuals and 10 healthy unexposed individuals were recruited as controls.

RESULTS: Patients were clinically classified into CFS (n = 15), idiopathic chronic fatigue (n = 5), fatigue from other causes (n = 9) and recovered from fatigue (n = 10). There were statistically significant antigen specific differences between these Giardia exposed groups and unexposed controls. However, we did not find differences between the Giardia exposed fatigue classification groups with regard to CD4 T cell activation, proliferation or cytokine levels in 6 days cultured PBMCs. Interestingly, sCD40L was increased in patients with PI-CFS and other persons with fatigue after Giardia infection compared to the non-fatigued group, and correlated well with fatigue levels at the time of sampling.

CONCLUSION: Our data show antigen specific cellular immune responses in the groups previously exposed to Giardia and increased sCD40L in fatigued patients.

Source: Hanevik K, Kristoffersen E, Mørch K, Rye KP, Sørnes S, Svärd S, Bruserud Ø, Langeland N. Giardia-specific cellular immune responses in post-giardiasis chronic fatigue syndrome. BMC Immunol. 2017 Jan 28;18(1):5. doi: 10.1186/s12865-017-0190-3.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5279576/ (Full article)

Mechanisms Explaining Muscle Fatigue and Muscle Pain in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): a Review of Recent Findings

Abstract:

PURPOSE OF REVIEW: Here, we review potential causes of muscle dysfunction seen in many patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) such as the effects of oxidative and nitrosative stress (O&NS) and mitochondrial impairments together with reduced heat shock protein production and a range of metabolic abnormalities.

RECENT FINDINGS: Several studies published in the last few years have highlighted the existence of chronic O&NS, inflammation, impaired mitochondrial function and reduced heat shock protein production in many patients with ME/CFS. These studies have also highlighted the detrimental effects of chronically elevated O&NS on muscle functions such as reducing the time to muscle fatigue during exercise and impairing muscle contractility.

Mechanisms have also been revealed by which chronic O&NS and or impaired heat shock production may impair muscle repair following exercise and indeed the adaptive responses in the striated muscle to acute and chronic increases in physical activity. The presence of chronic O&NS, low-grade inflammation and impaired heat shock protein production may well explain the objective findings of increased muscle fatigue, impaired contractility and multiple dimensions of exercise intolerance in many patients with ME/CFS.

Source: Gerwyn M, Maes M. Mechanisms Explaining Muscle Fatigue and Muscle Pain in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): a Review of Recent Findings. Curr Rheumatol Rep. 2017 Jan;19(1):1. doi: 10.1007/s11926-017-0628-x. https://www.ncbi.nlm.nih.gov/pubmed/28116577

A systematic review of the association between fatigue and genetic polymorphisms

Abstract:

Fatigue is one of the most common and distressing symptoms, leading to markedly decreased quality of life among a large subset of patients with a variety of disorders. Susceptibility to fatigue may be influenced by genetic factors including single nucleotide polymorphisms (SNPs), especially in the regulatory regions, of relevant genes.

To further investigate the association of SNPs with fatigue in various patient populations, a systematic search was conducted on Pubmed, CINAHL, PsycINFO, and Sociological Abstracts Database for fatigue related-terms in combination with polymorphisms or genetic variation-related terms. Fifty papers in total met the inclusion and exclusion criteria for this analysis. These 50 papers were further classified into three subgroups for evaluation: chronic fatigue syndrome (CFS), cancer-related fatigue (CRF) and other disease-related fatigue.

SNPs in regulatory pathways of immune and neurotransmitter systems were found to play important roles in the etiologies of CFS, CRF and other disease-related fatigue. Evidence for associations between elevated fatigue and specific polymorphisms in TNFα, IL1b, IL4 and IL6 genes was revealed for all three subgroups of fatigue.

We also found CFS shared a series of polymorphisms in HLA, IFN-γ, 5-HT and NR3C1 genes with other disease-related fatigue, however these SNPs (excluding IFN-γ) were not found to be adequately investigated in CRF. Gaps in knowledge related to fatigue etiology and recommendations for future research are further discussed.

Source: Wang T, Yin J, Miller AH, Xiao C. A systematic review of the association between fatigue and genetic polymorphisms. Brain Behav Immun. 2017 Jan 12. pii: S0889-1591(17)30007-7. doi: 10.1016/j.bbi.2017.01.007. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28089639

Children’s experiences of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): a systematic review and meta-ethnography of qualitative studies

Abstract:

OBJECTIVE: To synthesis the qualitative studies of children’s experiences of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME).

DESIGN: Systematic review and meta-ethnography.

BACKGROUND: CFS/ME is an important disabling illness, with uncertain cause and prognosis. As a result, children with CFS/ME can find themselves living with greater uncertainty and stigma, exacerbating the impact of the condition. There is a growing body of qualitative research in CFS/ME, yet there has been no attempt to systematically synthesis the studies involving children.

METHODS: Studies exploring the experiences of children diagnosed with CFS/ME, published or unpublished, using qualitative methods were eligible. MEDLINE, EMBASE, PsycINFO and CINAHL databases were searched as well as grey literature, reference lists and contacting authors. Quality assessment was done independently using the Critical Appraisal Skills Programme (CASP) checklist. Studies were synthesised using techniques of meta-ethnography.

RESULTS: Ten studies involving 82 children with CFS/ME aged 8-18 were included. Our synthesis describes four third-order constructs within children’s experiences: (1) disruption and loss: physical, social and the self; (2) barriers to coping: suspension in uncertainty, problems with diagnosis and disbelief; (3) facilitators to coping: reducing uncertainty, credible illness narratives, diagnosis and supportive relationships and (4) hope, personal growth and recovery. CFS/ME introduces profound biographical disruption through its effects on children’s ability to socialise, perform school and therefore how they see their future. Unfamiliarity of the condition, problems with diagnosis and felt stigma prevent children from forming a new illness identity. Children adopt coping strategies such as building credible explanations for their illness.

CONCLUSIONS: Physical, social, emotional and self-dimensions of life should be included when treating and measuring outcomes from healthcare in paediatric CFS/ME. There is a need for greater recognition and diagnosis of childhood CFS/ME, specialist advice on activity management and improved communication between health and education providers to help children cope with their condition.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Source: Parslow RM, Harris S, Broughton J, Alattas A, Crawley E, Haywood K, Shaw A. Children’s experiences of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): a systematic review and meta-ethnography of qualitative studies. BMJ Open. 2017 Jan 13;7(1):e012633. doi: 10.1136/bmjopen-2016-012633. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5253584/ (Full article)

Metabolic profiling of a myalgic encephalomyelitis/chronic fatigue syndrome discovery cohort reveals disturbances in fatty acid and lipid metabolism

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) remains a continuum spectrum disease without biomarkers or simple objective tests, and therefore relies on a diagnosis from a set of symptoms to link the assortment of brain and body disorders to ME/CFS. Although recent studies show various affected pathways, the underlying basis of ME/CFS has yet to be established.

In this pilot study, we compare plasma metabolic signatures in a discovery cohort, 17 patients and 15 matched controls, and explore potential metabolic perturbations as the aftermath of the complex interactions between genes, transcripts and proteins.

This approach to examine the complex array of symptoms and underlying foundation of ME/CFS revealed 74 differentially accumulating metabolites, out of 361 (P < 0.05), and 35 significantly altered after statistical correction (Q < 0.15). The latter list includes several essential energy-related compounds which could theoretically be linked to the general lack of energy observed in ME/CFS patients. Pathway analysis points to a few pathways with high impact and therefore potential disturbances in patients, mainly taurine metabolism and glycerophospholipid metabolism, combined with primary bile acid metabolism, as well as glyoxylate and dicarboxylate metabolism and a few other pathways, all involved broadly in fatty acid metabolism.

Purines, including ADP and ATP, pyrimidines and several amino acid metabolic pathways were found to be significantly disturbed. Finally, glucose and oxaloacetate were two main metabolites affected that have a major effect on sugar and energy levels. Our work provides a prospective path for diagnosis and understanding of the underlying mechanisms of ME/CFS.

Source: Germain A, Ruppert D, Levine SM, Hanson MR. Metabolic profiling of a myalgic encephalomyelitis/chronic fatigue syndrome discovery cohort reveals disturbances in fatty acid and lipid metabolism. Mol Biosyst. 2017 Jan 31;13(2):371-379. doi: 10.1039/c6mb00600k. https://www.ncbi.nlm.nih.gov/pubmed/28059425

Treatment and management of chronic fatigue syndrome/myalgic encephalomyelitis: all roads lead to Rome

Abstract:

This review explores the current evidence on benefits and harms of therapeutic interventions in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and makes recommendations. CFS/ME is a complex, multi-system, chronic medical condition whose pathophysiology remains unknown. No established diagnostic tests exist nor are any FDA-approved drugs available for treatment. Because of the range of symptoms of CFS/ME, treatment approaches vary widely.

Studies undertaken have heterogeneous designs and are limited by sample size, length of follow-up, applicability and methodological quality. The use of rintatolimod and rituximab as well as counselling, behavioural and rehabilitation therapy programs may be of benefit for CFS/ME, but the evidence of their effectiveness is still limited. Similarly, adaptive pacing appears to offer some benefits, but the results are debatable: so is the use of nutritional supplements, which may be of value to CFS/ME patients with biochemically proven deficiencies.

To summarize, the recommended treatment strategies should include proper administration of nutritional supplements in CFS/ME patients with demonstrated deficiencies and personalized pacing programs to relieve symptoms and improve performance of daily activities, but a larger randomized controlled trial (RCT) evaluation is required to confirm these preliminary observations.

At present, no firm conclusions can be drawn because the few RCTs undertaken to date have been small-scale, with a high risk of bias, and have used different case definitions. Further, RCTs are now urgently needed with rigorous experimental designs and appropriate data analysis, focusing particularly on the comparison of outcomes measures according to clinical presentation, patient characteristics, case criteria and degree of disability (i.e. severely ill ME cases or bedridden).

Source: Castro-Marrero J, Sáez-Francàs N, Santillo D, Alegre J. Treatment and management of chronic fatigue syndrome/myalgic encephalomyelitis: all roads lead to Rome. Br J Pharmacol. 2017 Mar;174(5):345-369. doi: 10.1111/bph.13702. Epub 2017 Feb 1. https://www.ncbi.nlm.nih.gov/pubmed/28052319

Impaired calcium mobilization in natural killer cells from chronic fatigue syndrome/myalgic encephalomyelitis patients is associated with transient receptor potential melastatin 3 ion channels

Abstract:

Transient receptor potential melastatin subfamily 3 (TRPM3) ion channels play a role in calcium (Ca2+ ) cell signalling. Reduced TRPM3 protein expression has been identified in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) patients. However, the significance of TRPM3 and association with intracellular Ca2+ mobilization has yet to be determined.

Fifteen CFS/ME patients (mean age 48·82 ± 9·83 years) and 25 healthy controls (mean age 39·2 ± 12·12 years) were examined. Isolated natural killer (NK) cells were labelled with fluorescent antibodies to determine TRPM3, CD107a and CD69 receptors on CD56dim CD16+ NK cells and CD56bright CD16dim/- NK cells. Ca2+ flux and NK cytotoxicity activity was measured under various stimulants, including pregnenolone sulphate (PregS), thapsigargin (TG), 2-aminoethoxydiphenyl borate (2APB) and ionomycin.

Unstimulated CD56bright CD16dim/- NK cells showed significantly reduced TRPM3 receptors in CFS/ME compared with healthy controls (HC). Ca2+ flux showed no significant difference between groups. Moreover, PregS-stimulated CD56bright CD16dim/- NK cells showed a significant increase in Ca2+ flux in CFS/ME patients compared with HC. By comparison, unstimulated CD56dim CD16+ NK cells showed no significant difference in both Ca2+ flux and TRPM3 expression. PregS-stimulated CD56dim CD16+ NK cells increased TRPM3 expression significantly in CFS/ME, but this was not associated with a significant increase in Ca2+ flux.

Furthermore, TG-stimulated CD56dim CD16+ NK cells increased K562 cell lysis prior to PregS stimulation in CFS/ME patients compared with HC. Differential expression of TRPM3 and Ca2+ flux between NK cell subtypes may provide evidence for their role in the pathomechanism involving NK cell cytotoxicity activity in CFS/ME.

Source: Nguyen T, Johnston S, Clarke L, Smith P, Staines D, Marshall-Gradisnik S. Impaired calcium mobilization in natural killer cells from chronic fatigue syndrome/myalgic encephalomyelitis patients is associated with transient receptor potential melastatin 3 ion channels. Clin Exp Immunol. 2017 Feb;187(2):284-293. doi: 10.1111/cei.12882. Epub 2016 Nov 23. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5217865/ (Full article)