Patients' experiences and effects of non-pharmacological treatment for myalgic encephalomyelitis/chronic fatigue syndrome - a scoping mixed methods review.

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.

Unperturbed Cytotoxic Lymphocyte Phenotype and Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients.

Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) is a debilitating disorder linked to diverse intracellular infections as well as physiological stress. Cytotoxic lymphocytes combat intracellular infections. Their function is attenuated by stress. Despite numerous studies, the role of cytotoxic lymphocytes in ME/CFS remains unclear. Prompted by advances in the understanding of defects in lymphocyte cytotoxicity, the discovery of adaptive natural killer (NK) cell subsets associated with certain viral infections, and compelling links between stress, adrenaline, and cytotoxic lymphocyte function, we reassessed the role of cytotoxic lymphocytes in ME/CFS. Forty-eight patients from two independent cohorts fulfilling the Canada 2003 criteria for ME/CFS were evaluated with respect to cytotoxic lymphocyte phenotype and function. Results were compared to values from matched healthy controls. Reproducible differences between patients and controls were not found in cytotoxic lymphocyte numbers, cytotoxic granule content, activation status, exocytotic capacity, target cell killing, or cytokine production. One patient expressed low levels of perforin, explained by homozygosity for the PRF1 p.A91V variant. However, overall, this variant was present in a heterozygous state at the expected population frequency among ME/CFS patients. No single patient displayed any pathological patterns of cellular responses. Increased expansions of adaptive NK cells or deviant cytotoxic lymphocyte adrenaline-mediated inhibition were not observed. In addition, supervised dimensionality reduction analyses of the full, multidimensional datasets did not reveal any reproducible patient/control discriminators. In summary, employing sensitive assays and analyses for quantification of cytotoxic lymphocyte differentiation and function, cytotoxicity lymphocyte aberrances were not found among ME/CFS patients. These assessments of cytotoxic lymphocytes therefore do not provide useful biomarkers for the diagnosis of ME/CFS.