Prof Julia Newton of Newcastle University and Karl Morten of Oxford University talk about forging international collaborations in the field of M.E./CFS research.
Tag: 2017
VIDEO: CMRC Conference 2017 day 2 – Prof Jose Montoya
Prof Jose Montoya of Stanford University talks about his latest research involving Cytokines in the blood of people with M.E./CFS.
Counting The Cost – Chronic Fatigue Syndrome/Myalgic Encephalomyelitis
Foreword:
For the past 20 years there has been extensive argument in the UK about the causes and diagnostic criteria for this illness. For some considerable time, the conventional wisdom was that this illness was purely psychological in origin.
The World Health Organisation has clearly classified CFS/ME as a neurological disease in its International Classification of Diseases (ICD), section G93.3.
Despite this clarity, there is still a lack of universal agreement about CFS/ ME in the UK. This has led to a paralysis of research into both the biomedical causes of and treatments for CFS/ME, and the research that has been done has focused primarily on the psychological side.
The time has come for a proper research strategy for CFS/ME, looking at both bio-medical causes and treatments. In order to commence a dialogue with government and other interested parties, it is essential for everyone to be on the same page. To achieve that degree of agreement will be a challenge, but I believe the first step in that process is to start a new public conversation about this horrible illness.
The purpose of this report by the health think tank 2020health, sponsored by the Optimum Health Clinic, is to do just that. Nothing concentrates the mind like money. This is the first cost of illness study of CFS/ME to the UK economy combining direct costs (including primary and secondary care contacts, prescription and over the counter
medications, and complimentary treatments) and indirect costs (including work productivity losses, informal care and welfare payments). The results are staggering.
In commissioning this report, our hope is that we can:
* Demonstrate clearly all the costs of CFS/ME to the UK economy;
* Use this report to start a new public conversation about the illness;
* Start a dialogue with all interested parties to create a new strategy to research the bio-medical causes of and treatments for CFS/ME
You can read the full report HERE.
NIH announces centers for myalgic encephalomyelitis/chronic fatigue syndrome research
Press Release: NIH, September 27, 2017. The National Institutes of Health (NIH) will award four grants to establish a coordinated scientific research effort on myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The total cost of the projects for fiscal year 2017 will be over $7 million, with support from multiple NIH Institutes and Centers that are part of the Trans-NIH ME/CFS Working Group.
The grants will support the creation of a consortium made up of three Collaborative Research Centers (CRC) and a Data Management Coordinating Center (DMCC). The CRCs will each conduct independent research but will also collaborate on several projects, forming a network to help advance knowledge on ME/CFS. The data will be managed by the DMCC and will be shared among researchers within the CRCs and more broadly with the research community.
“These important grants will provide a strong foundation for expanding research in ME/CFS, and lead to knowledge about the causes and ways to treat people affected by this mysterious, heartbreaking, and debilitating disease,” said NIH Director Francis S. Collins, M.D., Ph.D.
ME/CFS, which affects more than 1 million Americans, is characterized by profound fatigue that does not improve with rest, and may include problems with thinking and memory, pain and a range of other symptoms that negatively impact everyday life. A key feature of the disease is post-exertional malaise, which is a worsening of symptoms following mental or physical activity. The disease can last for years or decades, with those most severely impacted ending up house- or bed-bound. It is unknown what causes the disease and there are no proven treatments.
“These grants will use innovative technologies and research methods to unravel this devastating disease, which we know so little about,” said Walter Koroshetz, M.D., director of NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and chair of the Trans-NIH ME/CFS Working Group.
A robust, single-injection method for targeted, broad-spectrum plasma metabolomics
Abstract:
BACKGROUND: Metabolomics is a powerful emerging technology for studying the systems biology and chemistry of health and disease. Current targeted methods are often limited by the number of analytes that can be measured, and/or require multiple injections.
METHODS: We developed a single-injection, targeted broad-spectrum plasma metabolomic method on a SCIEX Qtrap 5500 LC-ESI-MS/MS platform. Analytical validation was conducted for the reproducibility, linearity, carryover and blood collection tube effects. The method was also clinically validated for its potential utility in the diagnosis of chronic fatigue syndrome (CFS) using a cohort of 22 males CFS and 18 age- and sex-matched controls.
RESULTS: Optimization of LC conditions and MS/MS parameters enabled the measurement of 610 key metabolites from 63 biochemical pathways and 95 stable isotope standards in a 45-minute HILIC method using a single injection without sacrificing sensitivity. The total imprecision (CVtotal) of peak area was 12% for both the control and CFS pools. The 8 metabolites selected in our previous study (PMID: 27573827) performed well in a clinical validation analysis even when the case and control samples were analyzed 1.5 years later on a different instrument by a different investigator, yielding a diagnostic accuracy of 95% (95% CI 85-100%) measured by the area under the ROC curve.
CONCLUSIONS: A reliable and reproducible, broad-spectrum, targeted metabolomic method was developed, capable of measuring over 600 metabolites in plasma in a single injection. The method might be a useful tool in helping the diagnosis of CFS or other complex diseases.
Source: Li K, Naviaux JC, Bright AT, Wang L, Naviaux RK. A robust, single-injection method for targeted, broad-spectrum plasma metabolomics. Metabolomics. 2017;13(10):122. doi: 10.1007/s11306-017-1264-1. Epub 2017 Sep 4. https://www.ncbi.nlm.nih.gov/pubmed/28943831
Clinical and cost-effectiveness of the Lightning Process in addition to specialist medical care for paediatric chronic fatigue syndrome: randomised controlled trial
Editor’s Comment: Numerous critiques of the Lightning Process have been made by physicians, medical practitioners, and patient organizations. There are cases in which LP has resulted in long-lasting physical harm. (You can read about these cases here and here.) Dr. Charles Shepherd, an ME/CFS specialist, does not recommend LP for any ME/CFS patients.
Abstract:
OBJECTIVE: Investigate the effectiveness and cost-effectiveness of the Lightning Process (LP) in addition to specialist medical care (SMC) compared with SMC alone, for children with chronic fatigue syndrome (CFS)/myalgic encephalitis (ME).
DESIGN: Pragmatic randomised controlled open trial. Participants were randomly assigned to SMC or SMC+LP. Randomisation was minimised by age and gender.
SETTING: Specialist paediatric CFS/ME service.
PATIENTS: 12-18 year olds with mild/moderate CFS/ME.
MAIN OUTCOME MEASURES: The primary outcome was the the 36-Item Short-Form Health Survey Physical Function Subscale (SF-36-PFS) at 6 months. Secondary outcomes included pain, anxiety, depression, school attendance and cost-effectiveness from a health service perspective at 3, 6 and 12 months.
RESULTS: We recruited 100 participants, of whom 51 were randomised to SMC+LP. Data from 81 participants were analysed at 6 months. Physical function (SF-36-PFS) was better in those allocated SMC+LP (adjusted difference in means 12.5(95% CI 4.5 to 20.5), p=0.003) and this improved further at 12 months (15.1 (5.8 to 24.4), p=0.002). At 6 months, fatigue and anxiety were reduced, and at 12 months, fatigue, anxiety, depression and school attendance had improved in the SMC+LP arm. Results were similar following multiple imputation. SMC+LP was probably more cost-effective in the multiple imputation dataset (difference in means in net monetary benefit at 12 months £1474(95% CI £111 to £2836), p=0.034) but not for complete cases.
CONCLUSION: The LP is effective and is probably cost-effective when provided in addition to SMC for mild/moderately affected adolescents with CFS/ME.
TRIAL REGISTRATION NUMBER: ISRCTN81456207.
© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Source: Crawley EM, Gaunt DM, Garfield K, Hollingworth W, Sterne JAC, Beasant L, Collin SM, Mills N, Montgomery AA. Clinical and cost-effectiveness of the Lightning Process in addition to specialist medical care for paediatric chronic fatigue syndrome: randomised controlled trial. Arch Dis Child. 2017 Sep 20. pii: archdischild-2017-313375. doi: 10.1136/archdischild-2017-313375. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28931531
To Serve or Not to Serve: Ethical and Policy Implications
Abstract:
The Institute of Medicine (IOM) is one of the nation’s more influential health-related non-profit organizations. It plays a large role in shaping health policy by commissioning panels to develop “white papers” describing research and recommendations on a variety of health topics. These white paper publications are often used to help make policy decisions at the legislative and executive levels. Such a prominent institution might seem like a natural ally for policy-related collaborative efforts. As community psychologists, we strongly endorse efforts to positively influence public policy at the national level. However, while serving on influential panels and commissions like the IOM might seem to be very much part of the ethos of our discipline, there are occasions when such institutions are pursuing a mission that inadvertently has the potential to instigate divisive friction among community activists and organizations.
A case study is presented whereby I describe my decision not to accept an invitation to serve on a controversial IOM panel. I explore the ethical challenges regarding maintaining my independence from this institution and its attempt to redefine chronic fatigue syndrome (CFS) and myalgic encephalomyelitis (ME), as well as the process of searching for alternative avenues for collaborating with community activists to influence policy related to these debilitating illnesses.
© Society for Community Research and Action 2017.
Source: Jason LA. To Serve or Not to Serve: Ethical and Policy Implications. Am J Community Psychol. 2017 Sep 18. doi: 10.1002/ajcp.12181. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28921637
Depression, evening salivary cortisol and inflammation in chronic fatigue syndrome: A psychoneuroendocrinological structural regression model
Abstract:
INTRODUCTION: Chronic Fatigue Syndrome (CFS) is a poorly understood illness that is characterized by diverse somatic symptoms, hypothalamic pituitary adrenal (HPA) axis dysfunction and heightened inflammatory indicators. These symptoms are often exacerbated and accompanied by psychological distress states and depression. Since depression is known to be associated with HPA axis dysfunction and greater inflammation, a psychoneuroendocrinological (PNE) model of inflammation was examined in persons diagnosed with CFS in order to uncover underlying biopsychosocial mechanisms in this poorly understood chronic illness.
METHODS: Baseline data were drawn from two randomized controlled trials testing the efficacy of different forms of psychosocial intervention, and included psychological questionnaires, di-urnal salivary cortisol, and blood samples. Data were analyzed with structural equation modeling (SEM).
RESULTS: The sample (N=242) was mostly middle-aged (Mage=49.36±10.9, range=20-73years), Caucasian (70.1%), female (84.6%), highly educated (88.6% completed some college, college, or graduate program), and depressed (CES-D M=23.87±12.02, range 2-57). The SEM supporting a psychoneuroendocrinological model of immune dysregulation in CFS fit the data χ2 (12)=17.725, p=0.1243, RMSEA=0.043, CFI=0.935, SRMR=0.036. Depression was directly related to evening salivary cortisol and inflammation, such that higher evening cortisol predicted greater depressive symptoms (β=0.215, p<0.01) and higher pro-inflammatory cytokines (interleukin-2 [IL-2], IL-6, and tumor necrosis factor-alpha [TNF-α] levels (β=0.185, p<0.05), when controlling for covariates.
DISCUSSION: Results highlight the role of depression, cortisol and inflammation in possible biological mechanisms involved in the pathophysiology of CFS. Time-lagged, longitudinal analyses are needed to fully explore these relationships.
Copyright © 2017. Published by Elsevier B.V.
Source: Milrad SF, Hall DL, Jutagir DR, Lattie EG, Czaja SJ, Perdomo DM, Fletcher MA, Klimas N, Antoni MH. Depression, evening salivary cortisol and inflammation in chronic fatigue syndrome: A psychoneuroendocrinological structural regression model. Int J Psychophysiol. 2017 Sep 13. pii: S0167-8760(17)30162-9. doi: 10.1016/j.ijpsycho.2017.09.009. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28918107
Altered right anterior insular connectivity and loss of associated functions in adolescent chronic fatigue syndrome
Abstract:
Impairments in cognition, pain intolerance, and physical inactivity characterize adolescent chronic fatigue syndrome (CFS), yet little is known about its neurobiology. The right dorsal anterior insular (dAI) connectivity of the salience network provides a motivational context to stimuli. In this study, we examined regional functional connectivity (FC) patterns of the right dAI in adolescent CFS patients and healthy participants.
Eighteen adolescent patients with CFS and 18 aged-matched healthy adolescent control participants underwent resting-state functional magnetic resonance imaging. The right dAI region of interest was examined in a seed-to-voxel resting-state FC analysis using SPM and CONN toolbox. Relative to healthy adolescents, CFS patients demonstrated reduced FC of the right dAI to the right posterior parietal cortex (PPC) node of the central executive network. The decreased FC of the right dAI-PPC might indicate impaired cognitive control development in adolescent CFS. Immature FC of the right dAI-PPC in patients also lacked associations with three known functional domains: cognition, pain and physical activity, which were observed in the healthy group. These results suggest a distinct biological signature of adolescent CFS and might represent a fundamental role of the dAI in motivated behavior.
Source: Wortinger LA, Glenne Øie M, Endestad T, Bruun Wyller V. Altered right anterior insular connectivity and loss of associated functions in adolescent chronic fatigue syndrome. PLoS One. 2017 Sep 7;12(9):e0184325. doi: 10.1371/journal.pone.0184325. ECollection 2017. https://www.ncbi.nlm.nih.gov/pubmed/28880891
What treatments work for anxiety in children with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME)? Systematic review
Abstract:
OBJECTIVES: Anxiety is more prevalent in children with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) than in the general population. A systematic review was carried out to identify which treatment methods are most effective for children with CFS and anxiety.
DESIGN: Systematic review using search terms entered into the Cochrane library and Ovid to search the databases Medline, Embase and psychINFO.
PARTICIPANTS: Studies were selected if participants were <18 years old, diagnosed with CFS/ME (using US Centers for Disease Control and Prevention, the National Institute for Health and Care Excellence or Oxford criteria) and had a valid assessment of anxiety.
INTERVENTIONS: We included observational studies and randomised controlled trials.
COMPARISON: Any or none.
OUTCOMES: Change in anxiety diagnostic status and/or change in anxiety severity on a validated measure of anxiety from pretreatment to post-treatment.
RESULTS: The review identified nine papers from eight studies that met the inclusion criteria. None of the studies specifically targeted anxiety but six studies tested an intervention and measured anxiety as a secondary outcome. Of these studies, four used a cognitive behavioural therapy (CBT)-type approach to treat CFS/ME, one used a behavioural approach and one compared a drug treatment, gammaglobulin with a placebo. Three of the CBT-type studies described an improvement in anxiety as did the trial of gammaglobulin. As none of the studies stratified outcomes according to anxiety diagnostic status or severity, we were unable to determine whether anxiety changed prognosis or whether treatments were equally effective in those with comorbid anxiety compared with those without.
CONCLUSION: We do not know what treatment should be offered for children with both anxiety and CFS/ME. Further research is therefore required to answer this question.
TRIAL REGISTRATION NUMBER: This review was registered on Prospective Register of Systematic Review Protocols (PROSPERO) and the protocol is available from http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42016043488.
© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Source: Stoll SVE, Crawley E, Richards V, Lal N, Brigden A, Loades ME. What treatments work for anxiety in children with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME)? Systematic review. BMJ Open. 2017 Sep 5;7(9):e015481. doi: 10.1136/bmjopen-2016-015481. https://www.ncbi.nlm.nih.gov/pubmed/28877941