Factors associated with work status in chronic fatigue syndrome

Abstract:

BACKGROUND: Work status in people with chronic fatigue syndrome (CFS) has not been extensively researched.

AIMS: To explore occupational outcomes in patients with CFS by socio-demographic, well-being and disease characteristics.

METHODS: We assessed cross-sectional data from patients attending a UK specialist CFS treatment service between 1 January 2007 and 31 December 2014. The main outcome was self-reported current employment status: currently in employment, temporarily interrupted employment or permanently interrupted employment. Other variables included sex, age, ethnicity, education, marital status, CFS duration, fatigue severity, anxiety, depression, activity limitations and functional impairment. We used multinominal logistic regression models to identify factors associated with current work status.

RESULTS: Two hundred and seventy-nine (55%) patients were currently working, with 83 (16%) reporting temporarily interrupted employment and 146 (29%) stopping work altogether. Factors strongly associated with permanently interrupted employment were older age (adjusted odds ratio (AOR) 5.24; 95% CI 2.67-10.28), poorer functioning (AOR 6.41; 95% CI 3.65-11.24) and depressive symptoms (AOR 2.89; 95% CI 1.82-4.58) compared to patients currently working. Higher educated patients (AOR 0.60; 95% CI 0.37-0.97) and being in a relationship (AOR 0.34; 95% CI 0.21-0.54) were associated with being currently employed. Anxiety symptoms were common; 230 patients (45%) met caseness criteria.

CONCLUSIONS: Many patients with CFS were not working. This was exacerbated by high levels of depressive symptoms. Health professionals should assess co-morbid mental health conditions and consider treatment options when patients with CFS present themselves. The early involvement of occupational health practitioners is recommended to maximize the chances of maintaining employment.

© The Author(s) 2019. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Source: Stevelink SAM, Fear NT, Hotopf M, Chalder T. Factors associated with work status in chronic fatigue syndrome. Occup Med (Lond). 2019 Aug 3. pii: kqz108. doi: 10.1093/occmed/kqz108. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31375832

Symptom frequency and development of a generic functional disorder symptom scale suitable for use in studies of patients with irritable bowel syndrome, fibromyalgia syndrome or chronic fatigue syndrome

Abstract:

OBJECTIVES: To describe the extent to which irritable bowel syndrome (IBS), fibromyalgia syndrome (FMS), and chronic fatigue syndrome (CFS) exhibit symptom overlap, and to validate a patient-derived, generic symptom questionnaire.

METHODS: A patient-derived 61-item symptom-frequency questionnaire was completed by participants recruited through IBS, FMS and CFS self-help websites. Principal axis factor analysis with oblimin rotation was performed separately for those reporting an IBS, FMS or CFS diagnosis.

RESULTS: Questionnaires were completed by 1751 participants of whom 851 reported more than one of the three diagnoses. Stomach pain on at least a weekly basis was reported by 79% of IBS, 52% of FMS, and 43% of CFS single diagnosis participants. Pain increasing the day after activity was reported by 32% of IBS, 94% of FMS, and 85% of CFS single diagnosis participants. Waking still tired at least once weekly was reported by 75% of IBS, 97% of FMS, and 95% of CFS single diagnosis participants. Exploratory factor analysis produced consistent results across all three diagnostic groups, the 61 items loading on 12 correlated factors with a single higher order factor on which all items loaded. Frequency analysis led to the rejection of one item (cold sores on or near lips), and freeform reporting by participants of additional symptoms identified an additional five, namely, restless legs, hair loss/brittle hair/thinning, dizziness/balance problems, blurred vision and urination problems.

CONCLUSIONS: IBS, FMS and CFS are polysymptomatic spectrum disorders with a wide range of overlapping symptoms, many of which are unrelated to diagnostic criteria. Frequency analysis and factor analysis confirm the validity of using the same questionnaire across different diagnostic categories. The 65-item general symptom questionnaire (GSQ-65) is a valid generic symptom scale suitable for assessing the many different symptoms of people with IBS, FMS and CFS.

Source: Hyland ME, Bacon AM, Lanario JW, Davies AF. Symptom frequency and development of a generic functional disorder symptom scale suitable for use in studies of patients with irritable bowel syndrome, fibromyalgia syndrome or chronic fatigue syndrome. Chronic Dis Transl Med. 2019 Jun 24;5(2):129-138. doi: 10.1016/j.cdtm.2019.05.003. eCollection 2019 Jun. https://www.sciencedirect.com/science/article/pii/S2095882X18300987?via%3Dihub (Full article)

A perspective on causation of the chronic fatigue syndrome by considering its nosology

Abstract:

The causes of chronic fatigue syndrome (CFS) remain unknown, with many failures to replicate new findings. This may be because the condition is hard to diagnose, difficult to classify, or because of its heterogeneous nature. Authors have problems in differentiating CFS from myalgic encephalomyelitis (ME), which leads many to label it as a hybrid CFS/ME or ME/CFS. Attempts to validate the many published criterion-based definitions have ended in failure. The International Classification of Diseases provide several different descriptions to choose from, although the latest 11th edition has narrowed this down. This paper describes conventional attempts to define and classify the illness, suggesting that this may be what leads to a failure to replicate putative causes. The approach to CFS/ME may require a shift in the assumption that the illness is homogeneous. An alternative approach is provided by studies suggesting that the condition is heterogeneous. ‘

CONCLUSION: The way forward may be to be over-inclusive regarding the diagnosis as a first step, while subdividing the condition into likely subgroups as a means of finding valid and reliable associations with potential causes. Studies of aetiology must involve prospective designs since cross-sectional studies cannot inform either aetiology or pathophysiology.

© 2019 John Wiley & Sons, Ltd.

Source: White PD. A perspective on causation of the chronic fatigue syndrome by considering its nosology. J Eval Clin Pract. 2019 Aug 1. doi: 10.1111/jep.13240. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31373106

General theory of inflammation: patient self-administration of hydrocortisone safely achieves superior control of hydrocortisone-responding disorders by matching dosage with symptom intensity

Abstract:

Objective: To determine if patient self-administration of hydrocortisone will safely achieve superior symptom control for all hydrocortisone-responding disorders as it does for Addison’s disease and rheumatoid arthritis.

Methods: Two thousand four hundred and twenty-eight participants with hydrocortisone-responding disorders were brought to a minimum symptom state using daily administered hydrocortisone tablets in a 24-week, open study. Thereafter, participants used 5-day, low-dose hydrocortisone regimens to quench subsequent disorder exacerbations (flares) to maintain the minimum symptom state. Stressors such as emotional traumas, infections, allergies, and injuries were minimized to reduce disorder intensity, hydrocortisone consumption, and participant discomfort.

Results: Two thousand fifteen participants, 601 with fibromyalgia, 579 with osteoarthritis, 246 with rheumatoid arthritis, 226 with undifferentiated arthritis, 75 with back pain, 51 with Parkinson’s disease, 44 with polymyalgia rheumatica, 25 with neuropathy, 25 with chronic fatigue syndrome, 25 with dementia, 21 with migraine headache, 19 with multiple sclerosis, and 78 with other disorders completed the 24-week study to achieve a composite average symptom improvement of 76% with equal response rates. The participants averaged ingesting 12 mg of hydrocortisone per day. No significant adverse reactions were observed.

Conclusions: Patient self-administration of hydrocortisone safely achieves superior symptom control for 38 hydrocortisone-responding disorders at equal rates and symptom improvements to confirm and amplify an earlier double-blind study finding on rheumatoid arthritis. These results are consistent with the body having an inflammation control system and chronic inflammation being a disorder unto itself with differing symptoms sets dependent on its location.

Clinical Trials Government Identifier: NCT03558971.

Source: Irwin JB, Baldwin AL, Stenberg VI. General theory of inflammation: patient self-administration of hydrocortisone safely achieves superior control of hydrocortisone-responding disorders by matching dosage with symptom intensity. J Inflamm Res. 2019 Jun 13;12:161-166. doi: 10.2147/JIR.S195165. eCollection 2019. https://www.dovepress.com/general-theory-of-inflammation-patient-self-administration-of-hydrocor-peer-reviewed-article-JIR (Full article)

The IDO Metabolic Trap Hypothesis for the Etiology of ME/CFS

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating noncommunicable disease brandishing an enormous worldwide disease burden with some evidence of inherited genetic risk. Absence of measurable changes in patients’ standard blood work has necessitated ad hoc symptom-driven therapies and a dearth of mechanistic hypotheses regarding its etiology and possible cure. A new hypothesis, the indolamine-2,3-dioxygenase (IDO) metabolic trap, was developed and formulated as a mathematical model.

The historical occurrence of ME/CFS outbreaks is a singular feature of the disease and implies that any predisposing genetic mutation must be common. A database search for common damaging mutations in human enzymes produces 208 hits, including IDO2 with four such mutations. Non-functional IDO2, combined with well-established substrate inhibition of IDO1 and kinetic asymmetry of the large neutral amino acid transporter, LAT1, yielded a mathematical model of tryptophan metabolism that displays both physiological and pathological steady-states. Escape from the pathological one requires an exogenous perturbation.

This model also identifies a critical point in cytosolic tryptophan abundance beyond which descent into the pathological steady-state is inevitable. If, however, means can be discovered to return cytosolic tryptophan below the critical point, return to the normal physiological steady-state is assured. Testing this hypothesis for any cell type requires only labelled tryptophan, a means to measure cytosolic tryptophan and kynurenine, and the standard tools of tracer kinetics.

Source: Alex A. Kashi, Ronald W. Davis and Robert D. Phair. The IDO Metabolic Trap Hypothesis for the Etiology of ME/CFS. Diagnostics 2019, 9(3), 82; https://doi.org/10.3390/diagnostics9030082 https://www.mdpi.com/2075-4418/9/3/82/htm (Full article)

Rethinking ME/CFS Diagnostic Reference Intervals via Machine Learning, and the Utility of Activin B for Defining Symptom Severity

Abstract:

Biomarker discovery applied to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a disabling disease of inconclusive aetiology, has identified several cytokines to potentially fulfil a role as a quantitative blood/serum marker for laboratory diagnosis, with activin B a recent addition. We explored further the potential of serum activin B as a ME/CFS biomarker, alone and in combination with a range of routine test results obtained from pathology laboratories.

Previous pilot study results showed that activin B was significantly elevated for the ME/CFS participants compared to healthy (control) participants. All the participants were recruited via CFS Discovery and assessed via the Canadian/International Consensus Criteria. A significant difference for serum activin B was also detected for ME/CFS and control cohorts recruited for this study, but median levels were significantly lower for the ME/CFS cohort.

Random Forest (RF) modelling identified five routine pathology blood test markers that collectively predicted ME/CFS at ≥62% when compared via weighted standing time (WST) severity classes. A closer analysis revealed that the inclusion of activin B to the panel of pathology markers improved the prediction of mild to moderate ME/CFS cases. Applying correct WST class prediction from RFA modelling, new reference intervals were calculated for activin B and associated pathology markers, where 24-h urinary creatinine clearance, serum urea and serum activin B showed the best potential as diagnostic markers. While the serum activin B results remained statistically significant for the new participant cohorts, activin B was found to also have utility in enhancing the prediction of symptom severity, as represented by WST class.

Source: Lidbury BA, Kita B, Richardson AM, Lewis DP, Privitera E, Hayward S, de Kretser D, Hedger M. Rethinking ME/CFS Diagnostic Reference Intervals via Machine Learning, and the Utility of Activin B for Defining Symptom Severity. Diagnostics (Basel). 2019 Jul 19;9(3). pii: E79. doi: 10.3390/diagnostics9030079. https://www.mdpi.com/2075-4418/9/3/79 (Full article)

The development of a short form of the DePaul Symptom Questionnaire

Abstract:

PURPOSE/OBJECTIVE: The DePaul Symptom Questionnaire (DSQ) is a widely used instrument that assesses common symptoms of myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS). The DSQ has strong psychometric properties; however, it consists of 99 items, and the energy limitations and cognitive difficulties experienced by individuals with ME and CFS may hinder their ability to easily complete the questionnaire.

METHOD: The current study examined symptom prevalence and discriminative ability to develop a short form of the DSQ (DSQ-SF).

RESULTS: The resulting short form questionnaire consists of 14 items that were highly prevalent among individuals with ME and CFS. Additionally, the items demonstrated the ability to differentiate individuals with ME and CFS from adult controls and, to a lesser extent, individuals with multiple sclerosis.

CONCLUSIONS/IMPLICATIONS: The DSQ-SF may serve as an effective, brief screening tool for symptoms of ME and CFS.

(PsycINFO Database Record (c) 2019 APA, all rights reserved).

Source: Sunnquist M, Lazarus S, Jason LA. The development of a short form of the DePaul Symptom Questionnaire. Rehabil Psychol. 2019 Jul 18. doi: 10.1037/rep0000285. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31318234

Epstein-Barr virus (EBV) reactivation and therapeutic inhibitors

Abstract:

Epstein-Barr virus (EBV) is a ubiquitous human virus which infects almost all humans during their lifetime and following the acute phase, persists for the remainder of the life of the individual. EBV infects B lymphocytes leading to their immortalisation, with persistence of the EBV genome as an episome. In the latent phase, EBV is prevented from reactivating through efficient cytotoxic cellular immunity.

EBV reactivates (lytic phase) under conditions of psychological stress with consequent weakening of cellular immunity, and EBV reactivation has been shown to occur in a subset of individuals with each of a variety of cancers, autoimmune diseases, the autoimmune-like disease, chronic fatigue syndrome/myalgic encephalitis and under other circumstances such as being an inpatient in an intensive care unit.

Chronic EBV reactivation is an important mechanism in the pathogenesis of many such diseases, yet is rarely tested for in immunocompetent individuals. This review summarises the pathogenesis of EBV infection, EBV reactivation and its role in disease, and methods which may be used to detect it. Known inhibitors of EBV reactivation and replication are discussed, including drugs licensed for treatment of other herpesviruses, licensed or experimental drugs for various other indications, compounds at an early stage of drug development and nutritional constituents such as vitamins and dietary supplements.

Source: Kerr JR. Epstein-Barr virus (EBV) reactivation and therapeutic inhibitors. J Clin Pathol. 2019 Jul 17. pii: jclinpath-2019-205822. doi: 10.1136/jclinpath-2019-205822. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31315893

Pathological Mechanisms Underlying Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

The underlying molecular basis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is not well understood. Characterized by chronic, unexplained fatigue, a disabling payback following exertion (“post-exertional malaise”) and variably presenting, multi-system symptoms, ME/CFS is a complex disease which demands concerted biomedical investigation from disparate fields of expertise.

ME/CFS research and patient treatment have been challenged by the lack of diagnostic biomarkers and finding these is a prominent direction of current work. Despite these challenges, modern research demonstrates a tangible biomedical basis for the disorder across many body systems. This evidence is largely comprised of disturbances to immunological and inflammatory pathways, autonomic and neurologic systems, abnormalities in muscle and mitochondrial function, shifts in metabolism, and gut physiology or gut microbiome disturbances. It is possible that these threads are together entangled as parts of an underlying molecular pathology reflecting a far-reaching homeostatic shift affecting each of these systems.

Due to the variability of non-overlapping symptom presentation or precipitating events such as infection or other bodily stresses, the initiation of body-wide pathological cascades with similar outcomes stemming from different causes may be implicated in the condition. Patient stratification to account for this heterogeneity is therefore one important consideration during exploration of potential diagnostic developments.

Source: Missailidis, D.; Annesley, S.; Fisher, P. Pathological Mechanisms Underlying Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Preprints 2019, 2019070196 (doi: 10.20944/preprints201907.0196.v1). https://www.preprints.org/manuscript/201907.0196/v1

Red blood cell biomechanics in Chronic Fatigue Syndrome

INTRODUCTION:

Chronic Fatigue Syndrome (CFS) is a multi-systemic illness of unknown etiology, affecting millions worldwide [1], with the capacity to persist for several years. It is characterized by persistent or relapsing unexplained fatigue of at least 6 months’ duration that is not alleviated by rest. CFS can be debilitating, and its clinical definition includes a broad cluster of symptoms and signs that give it its distinct character, and its diagnosis is based on these characteristic symptom patterns including cognitive impairment, post-exertional malaise, unrefreshing sleep, headache, hypersensitivity to noise, light or certain food items. Although an abnormal profile of circulating proinflammatory cytokines, and the presence of chronic oxidative and nitrosative stresses have been identified and correlated with severity in CFS [2], there are no reliable molecular or cellular biomarkers of the disease.

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Source: Saha, Amit & R. Schmidt, Brendan & Kumar, Arun & Saadat, Amir & C. Suja, Vineeth & Nguyen, Vy & K. Do, Justin & Ho, Wendy & Nemat-Gorgani, Mohsen & Shaqfeh, Eric & Ramasubrmanian, Anand & Davis, Ronald. (2019). Red Blood Cell Biomechanics in Chronic Fatigue Syndrome. Summer Biomechanics, Bioengineering and Biotransport Conference. June 25 -28, Seven Springs, PA, USA