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Concept: Fatigue

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Myalgic Encephalopathy/Chronic Fatigue Syndrome (ME/CFS) is a disease of unknown etiology. We previously reported a pilot case series followed by a small, randomized, placebo-controlled phase II study, suggesting that B-cell depletion using the monoclonal anti-CD20 antibody rituximab can yield clinical benefit in ME/CFS.

Concepts: Lymphocyte, Medicine, Clinical trial, The Canon of Medicine, Leukemia, Fibromyalgia, Fatigue, Chronic fatigue syndrome

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Background: Chronic fatigue syndrome (CFS) is relatively common and disabling. Over 8000 patients attend adult services each year, yet little is known about the outcome of patients attending NHS services. AIM: Investigate the outcome of patients with CFS and what factors predict outcome. DESIGN: Longitudinal patient cohort. METHODS: We used data from six CFS/ME (myalgic encephalomyelitis) specialist services to measure changes in fatigue (Chalder Fatigue Scale), physical function (SF-36), anxiety and depression (Hospital Anxiety and Depression Scale) and pain (visual analogue pain rating scale) between clinical assessment and 8-20 months of follow-up. We used multivariable linear regression to investigate baseline factors associated with outcomes at follow-up.Results: Baseline data obtained at clinical assessment were available for 1643 patients, of whom 834 (51%) had complete follow-up data. There were improvements in fatigue [mean difference from assessment to outcome: -6.8; 95% confidence interval (CI) -7.4 to -6.2; P < 0.001]; physical function (4.4; 95% CI 3.0-5.8; P < 0.001), anxiety (-0.6; 95% CI -0.9 to -0.3; P < 0.001), depression (-1.6; 95% CI -1.9 to -1.4; P < 0.001) and pain (-5.3; 95% CI -7.0 to -3.6; P < 0.001). Worse fatigue, physical function and pain at clinical assessment predicted a worse outcome for fatigue at follow-up. Older age, increased pain and physical function at assessment were associated with poorer physical function at follow-up. CONCLUSION: Patients who attend NHS specialist CFS/ME services can expect similar improvements in fatigue, anxiety and depression to participants receiving cognitive behavioural therapy and graded exercise therapy in a recent trial, but are likely to experience less improvement in physical function. Outcomes were predicted by fatigue, disability and pain at assessment.

Concepts: Psychology, Clinical psychology, Fibromyalgia, Cognitive behavioral therapy, Fatigue, Prediction interval, Major depressive disorder, Chronic fatigue syndrome

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Fatigue is a common symptom in healthy and clinical populations, including cancer survivors. However, risk factors for cancer-related fatigue have not been identified. On the basis of research linking stress with other fatigue-related disorders, we tested the hypothesis that stress exposure during childhood and throughout the life span would be associated with fatigue in breast cancer survivors. Stress exposure was assessed using the Stress and Adversity Inventory, a novel computer-based instrument that assesses for 96 types of acute and chronic stressors that may affect health. Results showed that breast cancer survivors with persistent fatigue reported significantly higher levels of cumulative lifetime stress exposure, including more stressful experiences in childhood and in adulthood, compared to a control group of nonfatigued survivors. These findings identify a novel risk factor for fatigue in the growing population of cancer survivors and suggest targets for treatment.

Concepts: Epidemiology, Cancer, Breast cancer, Metastasis, Risk, The Canon of Medicine, Pleural effusion, Fatigue

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Chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME), is a severely debilitating condition of unknown etiology. The symptoms and risk factors of ME/CFS share features of accelerated aging implicated in several diseases. Using telomere length as a marker, this study was performed to test the hypothesis that ME/CFS is associated with accelerated aging.

Concepts: Telomere, Fibromyalgia, Fatigue, Chronic fatigue syndrome, Malaise

105

Clinically significant anxiety and depression are common in patients with cancer, and are associated with poor psychiatric and medical outcomes. Historical and recent research suggests a role for psilocybin to treat cancer-related anxiety and depression.

Concepts: Epidemiology, Disease, Randomized controlled trial, Symptoms, Illness, Doctor-patient relationship, Fatigue, Psychiatry

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Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is a common, severe condition affecting 0.2 to 0.4 per cent of the population. Even so, no recent international EQ-5D based health-related quality of life (HRQoL) estimates exist for ME/CFS patients. The main purpose of this study was to estimate HRQoL scores using the EQ-5D-3L with Danish time trade-off tariffs. Secondary, the aims were to explore whether the results are not influenced by other conditions using regression, to compare the estimates to 20 other conditions and finally to present ME/CFS patient characteristics for use in clinical practice.

Concepts: Virus, Fibromyalgia, Fatigue, Chronic fatigue syndrome, Malaise

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Cancer patients often develop chronic, clinically significant symptoms of depression and anxiety. Previous studies suggest that psilocybin may decrease depression and anxiety in cancer patients. The effects of psilocybin were studied in 51 cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety. This randomized, double-blind, cross-over trial investigated the effects of a very low (placebo-like) dose (1 or 3 mg/70 kg) vs. a high dose (22 or 30 mg/70 kg) of psilocybin administered in counterbalanced sequence with 5 weeks between sessions and a 6-month follow-up. Instructions to participants and staff minimized expectancy effects. Participants, staff, and community observers rated participant moods, attitudes, and behaviors throughout the study. High-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety. At 6-month follow-up, these changes were sustained, with about 80% of participants continuing to show clinically significant decreases in depressed mood and anxiety. Participants attributed improvements in attitudes about life/self, mood, relationships, and spirituality to the high-dose experience, with >80% endorsing moderately or greater increased well-being/life satisfaction. Community observer ratings showed corresponding changes. Mystical-type psilocybin experience on session day mediated the effect of psilocybin dose on therapeutic outcomes.

Concepts: Psychology, Symptoms, Illness, Meaning of life, Fatigue, Bipolar disorder

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About 150 human rhinovirus serotypes are responsible for more than 50 % of recurrent upper respiratory infections. Despite having similar 3D structures, some bind members of the low-density lipoprotein receptor family, some ICAM-1, and some use CDHR3 for host cell infection. This is also reflected in the pathways exploited for cellular entry. We found that even rhinovirus serotypes binding the same receptor can travel along different endocytic pathways and release their RNA genome into the cytosol at different locations. How this may account for distinct immune responses elicited by various rhinoviruses and the observed symptoms of the common cold is briefly discussed.

Concepts: Immune system, Asthma, Influenza, Otitis media, Fatigue, Upper respiratory tract infection, Common cold, Rhinovirus

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Intercontinental air travel can be stressful, especially for respiratory health. Elderberries have been used traditionally, and in some observational and clinical studies, as supportive agents against the common cold and influenza. This randomized, double-blind placebo-controlled clinical trial of 312 economy class passengers travelling from Australia to an overseas destination aimed to investigate if a standardised membrane filtered elderberry (Sambucus nigra L.) extract has beneficial effects on physical, especially respiratory, and mental health. Cold episodes, cold duration and symptoms were noted in a daily diary and assessed using the Jackson score. Participants also completed three surveys containing questions regarding upper respiratory symptoms (WURSS-21) and quality of life (SF-12) at baseline, just before travel and at 4-days after travel. Most cold episodes occurred in the placebo group (17 vs. 12), however the difference was not significant (p = 0.4). Placebo group participants had a significantly longer duration of cold episode days (117 vs. 57, p = 0.02) and the average symptom score over these days was also significantly higher (583 vs. 247, p = 0.05). These data suggest a significant reduction of cold duration and severity in air travelers. More research is warranted to confirm this effect and to evaluate elderberry’s physical and mental health benefits.

Concepts: Clinical trial, Influenza, Placebo, Fatigue, Upper respiratory tract infection, Common cold, Sambucus, Sambucus nigra

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Chronic fatigue syndrome (CFS) is a complex, multisystem disorder that can be disabling. CFS symptoms can be provoked by increased physical or cognitive activity, and by orthostatic stress. In preliminary work, we noted that CFS symptoms also could be provoked by application of longitudinal neural and soft tissue strain to the limbs and spine of affected individuals. In this study we measured the responses to a straight leg raise neuromuscular strain maneuver in individuals with CFS and healthy controls. We randomly assigned 60 individuals with CFS and 20 healthy controls to either a 15 minute period of passive supine straight leg raise (true neuromuscular strain) or a sham straight leg raise. The primary outcome measure was the symptom intensity difference between the scores during and 24 hours after the study maneuver compared to baseline. Fatigue, body pain, lightheadedness, concentration difficulties, and headache scores were measured individually on a 0-10 scale, and summed to create a composite symptom score. Compared to individuals with CFS in the sham strain group, those with CFS in the true strain group reported significantly increased body pain (P = 0.04) and concentration difficulties (P = 0.02) as well as increased composite symptom scores (all P = 0.03) during the maneuver. After 24 hours, the symptom intensity differences were significantly greater for the CFS true strain group for the individual symptom of lightheadedness (P = 0.001) and for the composite symptom score (P = 0.005). During and 24 hours after the exposure to the true strain maneuver, those with CFS had significantly higher individual and composite symptom intensity changes compared to the healthy controls. We conclude that a longitudinal strain applied to the nerves and soft tissues of the lower limb is capable of increasing symptom intensity in individuals with CFS for up to 24 hours. These findings support our preliminary observations that increased mechanical sensitivity may be a contributor to the provocation of symptoms in this disorder.

Concepts: Symptoms, Symptom, Tissues, Soft tissue, Fatigue, Post-concussion syndrome, Chronic fatigue syndrome, Straight leg raise