WAMES’ response to draft NICE ME/CFS guideline scope

NICE ME/CFS guideline consultation – WAMES’ response to draft scope

Before work on the revised guidelines for ME/CFS can commence, the scope of the discussions needs to be agreed. On 26th July 2018 WAMES submitted final comments on the proposed NICE guideline scope.

Our comments reflected the views of patients and carers in Wales and we are grateful to all who who have been in touch with us.  We asked for a number of points to be included or changed e.g.:

Description of ME

WAMES found the description of the illness to be misleading and lacking key pieces of information, which could perpetuate the difficulties GPs and others have in using the guideline to accurately identify and diagnose the condition. The description should include:

  • ME/CFS is a chronic and potentially disabling disorder causing considerable disruption to daily life, relationships, work and education which has been found to lead to  a poorer quality of life of than other chronic  illnesses  such as MS, serious depression etc.
  • The Post-exertional response is the key characteristic of ME, not fatigue i.e. Symptoms deteriorate following minor physical or mental exertion, often delayed by a day or more and taking longer than normal to recover from.
  • A wide range of symptoms are experienced, which fluctuate over the course of the illness.
  • Triggers include viral illness, reactions to medication and toxic poisoning
  • Key symptoms include unrefreshing sleep, flu-like malaise, pain, extreme exhaustion/ weakness/ fatigability, orthostatic intolerance, digestive and cognitive dysfunction

Target audience

As well as patients, carers, health and social care workers, we thought the guideline would be useful for Benefits assessors.

Research into ME/CFS

Although a lot is not known about the cause and nature of ME/CFS, we wish the scope to include a positive statement about the many preliminary findings from biomedical research and the  growing number of clues to dysfunction in a wide range of the body’s systems. This switch of emphasis from the psycho-social research will shape the attitudes of health professionals and their approach to diagnosis and management, and hopefully remove the stigma, misunderstanding and disbelief currently hampering doctor/patient relationships.

Outcomes of management and treatment

  • It is important that evidence for management and treatment approaches is based on research with well-defined participant cohorts
  • Potential for, and evidence of harm, should be considered when searching for and assessing the research evidence or effectiveness of treatment options
  • As well as measuring improvements of sleep, pain, fatigue etc. absence of relapse could be another outcome, indicating successful management of the post-exertional response
  • Improvements in function and symptoms should be measured objectively, where possible, not just by subjective questionnaires

Read the final draft scope

Read the Equality Impact Assessment

Read WAMES’ full response

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The importance of screening for suicide risk in chronic invisible illness

The Importance of Screening for Suicide Risk in Chronic Invisible Illness, by Cathy L Pedersen in Journal of Health Science & Education Vol 2(4): 1-5 2018

Abstract: 

Many people suffering from chronic invisible illnesses like chronic fatigue syndrome/ myalgic encephalomyeletis (CFS/ME), fibromyalgia, Lyme disease, and postural orthostatic tachycardia syndrome (POTS) report increased suicidal ideation and past suicide attempts compared with the general population.

A number of factors contribute to suicide risk in chronic illness. Physical factors, like sleep disturbance and pain, as well as psychosocial issues like perceived burdensomeness (feeling like a burden to others), thwarted belongingness (lack of connection to a social group), loneliness, and depression may contribute to an increased suicide risk.

Healthcare practitioners are encouraged to actively screen for suicide risk in their chronically ill patients, and have a protocol in place to refer their patients to proper community resources.

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Checking our blind spots: current status of research evidence summaries in ME/CFS

Checking our blind spots: current status of research evidence summaries in ME/CFS, by Todd E Davenport, Staci R Stevens, J Mark VanNess, Jared Stevens, Christopher R Snell in British Journal of Sports Medicine, July 2018

Editorial:

The evidence-based practice (EBP) model hierarchically organises scientific information by level, from lowly case studies to lofty systematic reviews and clinical trials. Clinical trials best influence recommendations because they putatively have the greatest internal
validity.1

This assumption is based on sound research ethics, such as scientific competence and good faith actors, as well as observed differences in outcomes. An EBP blind spot emerges when fundamental assumptions are unmet.

Based on findings of a 2018 PEDro evidence summary in BJSM 2 and elsewhere,3 it now seems clear that scientific research in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) resides in a blind spot.

The paper goes on to discuss the flawed results of the PACE trial into GET and CBT before concluding:

EBP also includes patient perspectives. We should follow the example of engaged patient advocates and citizen scientists in ME/CFS by involving patients as advisory board members on trials and as reviewers on published evidence summaries. Community- based participatory research designs should be elevated to ensure information flows from bedside-to-lab bench, in addition to lab bench-to-bedside. By including evidence from patients in clinical decisions and research, we can begin to address the important blind spots in how we think about and implement EBP.

Read full article

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Reduced glycolytic reserve in isolated natural killer cells from ME/CFS patients

Reduced glycolytic reserve in isolated natural killer cells from Myalgic encephalomyelitis/ chronic fatigue syndrome patients: A preliminary investigation, by Thao Nguyen, D Staines, S Johnston, S Marshall-Gradisnik in Asian Pac J Allergy Immunol. 2018 Jul 8. [Epub ahead of print]

Abstract:

BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is medically unexplained post-exertional fatigue associated with significant reduction in natural killer cell (NK) cytotoxicity activity. Cytotoxic activity relies on glycolytic flux and mitochondrial respiration to fulfill energetic cellular demands. While mitochondrial dysfunction has been reported in ME/CFS patients, no previous investigation has examined the bioenergetic profile of isolated NK cells from ME/CFS patients.

OBJECTIVE: This study was to determine the metabolic function in resting NK cells from ME/CFS patients.

METHOD: Six ME/CFS patients (aged 50.33±4.95) were age and sex-matched with non-fatigued healthy controls (aged 50.00±5.04). Mitochondrial stress tests measured parameters of mitochondrial function in the NK cells including basal respiration, ATP production, proton leak, maximal respiration, spare respiratory capacity and bioenergetic health index. Glycolytic stress tests measured parameters of glycolytic function such as glycolytic reserve, glycolysis and glycolytic capacity in isolated NK cells from ME/CFS patients and healthy controls using an extracellular flux analyzer, Seahorse XFp.

RESULT: There was a significant reduction of glycolytic reserve in resting NK cells from ME/CFS patients (0.6±0.07 mpH/ min) compared with healthy control (2.25±1.3 mpH/min). Mitochondrial respiration in resting NK cells did not approach statistical significance between ME/CFS patients and healthy controls.

CONCLUSION: These findings suggest resting NK cells from ME/CFS patients have reduced ability to increase glycolytic flux to respond to high energetic demands for ATP production. Hence, the reduced glycolytic reserves we have identified in isolated resting isolated NK cells should be further investigated to assist in understanding ME/CFS pathogenesis.

Study finds reduced ability to respond to energy demands in ME patients’ immune systems

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Suicidal ideation in non-depressed individuals: the effects of a chronic, misunderstood illness

Suicidal ideation in non-depressed individuals: the effects of a chronic, misunderstood illness, by AR Devendorf, SL McManimen, LA Jason in Health Psychol. 2018 Jul 1:1359105318785450  [Epub ahead of print]

Abstract:

Chronic illness is a risk factor for suicide but is often explained with depression. Research has shown an increased suicide rate in patients with myalgic encephalomyelitis and chronic fatigue syndrome, but specific risk factors have been unexplored. We qualitatively analyzed responses from 29 patients who endorsed suicidal ideation but did not meet depression criteria.

Two themes were developed:

(1) feeling trapped and

(2) loss of self, loss of others, stigma and conflict.

Myalgic encephalomyelitis and chronic fatigue syndrome caused patients severe disability, restructured their lives, and inflicted serious pain. Participants emphasized that they were not depressed, but felt trapped by the lack of treatments available.

Read full article

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Nutritional modulation of the intestinal microbiota

Review abstract:

Nutritional modulation of the intestinal microbiota: future opportunities for the prevention and treatment of neuroimmune and neuroinflammatory disease, by Vincent C Lombardi, Kenny L De Meirleir, Krishnamurthy Subramanian, Sam M Nourani, Ruben K Dagda, Shannon L Delaney, András Palotás in The Journal of Nutritional Biochemistry, Volume 61, November 2018, Pages 1-16

The gut-brain-axis refers to the bidirectional communication between the enteric nervous system and the central nervous system. Mounting evidence supports the premise that the intestinal microbiota plays a pivotal role in its function and has led to the more common and perhaps more accurate term gut-microbiota-brain axis.

Numerous studies have identified associations between an altered microbiome and neuroimmune and neuroinflammatory diseases. In most cases, it is unknown if these associations are cause or effect; notwithstanding, maintaining or restoring homeostasis of the microbiota may represent future opportunities when treating or preventing these diseases.

In recent years, several studies have identified the diet as a primary contributing factor in shaping the composition of the gut microbiota, and in turn, the mucosal and systemic immune systems. In this review, we will discuss the potential opportunities and challenges with respect to modifying and shaping the microbiota through diet and nutrition in order to treat or prevent neuroimmune and neuroinflammatory disease.

Read full article

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New CFS test is 84% accurate

Medical News Today blog post, by Ana Sandoiu, 11 July 2018: New chronic fatigue syndrome test is 84 percent accurate

Myalgic encephalomyelitis/chronic fatigue syndrome does not currently have a diagnostic test. But this may soon change, as researchers have developed a test that can predict it with an unprecedented level of accuracy.

Currently, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is estimated to affect more than 1 million people in the United States, and up to 24 million people worldwide. This often debilitating condition is characterized by feelings of extreme exhaustion, muscle and joint pain, and insomnia, as well as difficulty concentrating or remembering things.

The causes of ME/CFS remain unknown, and in the absence of a proper diagnostic test for it, healthcare professionals have to exclude other disorders and examine a patient’s history before they can tell whether a person has ME/CFS or not.

However, this may soon change, as a team of researchers led by those at the Center for Infection and Immunity (CII) at Columbia University’s Mailman School of Public Health in New York City, NY, have engineered a highly accurate test for the disorder. The researchers detail their findings in a new study recently published in the journal Scientific
Reports. Dr. Dorottya Nagy-Szakal, a CII researcher, is the first author of the paper.

Engineering an ME/CFS diagnostic test

Dr. Nagy-Szakal and team examined the blood samples of 50 people with ME/CFS and compared them with those of 50 age-matched healthy controls. Using a special technique that identifies molecules by measuring their mass, the scientists found 562 metabolites that the ME/CFS patients had in common.

Metabolites are byproducts of the body’s metabolism – that is, its ability to process sugars, fats, and proteins. In the recent research, the scientists excluded metabolites resulting from antidepressants or other drugs.

Laboratory tests carried out by Dr. Nagy-Szakal and team revealed that certain metabolites were altered in a way that suggested that the patients’ mitochondria – which are the tiny organelles inside the cell responsible for turning nutrients into energy – were not functioning properly. The results are coherent with previous studies led by other researchers, as well as with research carried out by Dr. Nagy-Szakal and colleagues last year.

In 2017, the team found a distinct pattern of metabolites in people who had both irritable bowel syndrome (IBS) and ME/CFS. Other studies have reported that 35-90 percent of those with ME/CFS also have IBS. And in the new study, half of the ME/CFS patients also had IBS.

Test yields 84 percent accuracy

Dr. Nagy-Szakal and her colleagues combined biomarkers from both their  2017 study and their new study. The result was a predictive model with a 0.836 score, which translates into an accuracy rate of 84 percent.

‘This is a strong predictive model that suggests we’re getting close to the point where we’ll have lab tests that will allow us to say with a high level of certainty who has this disorder,’ explains Dr. Nagy-Szakal.

Corresponding author Dr. W. Ian Lipkin, director of CII and the National Institutes of Health (NIH) Center for Solutions for ME/CFS, also weighs in on the findings, saying,

‘We’re closing in on understanding how this disease works. We’re getting close to the point where we can develop animal models that will allow us to test various hypotheses, as well as potential therapies. For instance, some patients might benefit from probiotics to retune their gastrointestinal microflora or drugs that activate certain neurotransmitter systems.’

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Insights into ME/CFS phenotypes through comprehensive metabolomics

Research abstract:

Insights into myalgic encephalomyelitis/chronic fatigue syndrome phenotypes through comprehensive metabolomics, by Dorottya Nagy-Szakal, Dinesh K. Barupal, Bohyun Lee,
Xiaoyu Che, Brent L. Williams, Ellie J. R. Kahn, Joy E. Ukaigwe, Lucinda Bateman, Nancy G. Klimas, Anthony L. Komaroff, Susan Levine, Jose G. Montoya, Daniel L. Peterson, Bruce Levin, Mady Hornig, Oliver Fiehn, W. Ian Lipkin in Scientific Reports  8: 10056 (2018)

The pathogenesis of ME/CFS, a disease characterized by fatigue, cognitive dysfunction, sleep disturbances, orthostatic intolerance, fever, irritable bowel syndrome (IBS), and lymphadenopathy, is poorly understood.

We report biomarker discovery and topological analysis of plasma metabolomic, fecal bacterial metagenomic, and clinical data from 50 ME/CFS patients and 50 healthy controls. We confirm reports of altered plasma levels of choline, carnitine and complex lipid metabolites and demonstrate that patients with ME/CFS and IBS have increased plasma levels of ceramide.

Integration of fecal metagenomic and plasma metabolomic data resulted in a stronger predictive model of ME/CFS (cross-validated AUC = 0.836) than either metagenomic (cross-validated AUC = 0.745) or metabolomic (cross-validated AUC = 0.820) analysis alone.

Our findings may provide insights into the pathogenesis of ME/CFS and its subtypes and suggest pathways for the development of diagnostic and therapeutic strategies.

News medical, 10 July: Study identifies constellation of metabolites linked to ME/CFS

Science daily: Insights from metabolites get us closer to a test for chronic fatigue syndrome 

Review by Paul Whiteley PhD

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‘A Girl Behind Dark Glasses’ book by Jessica Taylor-Bearman

‘A Girl Behind Dark Glasses’ book by Jessica Taylor-Bearman

Book Description:

From a darkened world, bound by four walls, a young woman called Jessica tells the tale of her battle against the M.E Monster. The severest form of a neuro immune disease called Myalgic Encephalomyelitis went to war with her at just 15 years old. From beneath her dark glasses, Jessica glimpses a world far different from the one she remembers as a teenage school girl. This true story follows her path as she ends up living in hospital for years with tubes keeping her alive.

This harrowing story follows the highs and lows of the disease and being hospitalised, captured through her voice activated technology diary called `Bug’ that enables her to fulfil her dream of one day becoming an author.

It provides a raw, real-time honesty to the story that would be impossible to capture in hindsight.

Jo Moss’s review on her blog ‘The Mighty’: My Review of ‘A Girl Behind Dark Glasses’ as a Fellow ME Patient

I have just finished reading “A Girl Behind Dark Glasses: and I was so impressed I decided to write a review. “A Girl Behind Dark Glasses” is written by Jessica Taylor-Bearman and it’s an account of her life and struggles with a severe form of myalgic encephalomyelitis (ME).

“I was an inventor, a researcher, a model, and I travelled the world through my imagination. At that time, it was my only saving grace. I existed in a place I called Limbo Land, hovering between the conscious and the unconscious. I could hear my family talking to me, see images of them, yet I couldn’t reply or make sense of what they talked about.” – Jessica Taylor-Bearman

Order online from Jessica or from Amazon

Jessica’s website: Jaytay

Jessica’s book is available from Amazon   £4.99 for Kindle, £9.99 paper

 

Female First article, by Jessica Taylor-Bearman, 3 July 2018: 10 Things About Living With M.E. That You Want People To Know

Jessica Taylor-Bearman writes a piece for us upon the release of her new book A Girl Behind Dark Glasses.

I have been suffering with a chronic neuro immune disease for over twelve years called M.E. It stands for Myalgic Encephalomyelitis and remains very misunderstood in all aspects. You may have heard of it called by a multitude of different names including Chronic Fatigue Syndrome and sadly still, Yuppie Flu.

To find out more about the key things Jessica wants people to know read the full article

  1. There are so many things we do not know about M.E. but most importantly one thing we do know is that contrary to popular belief, M.E. is not ‘all in the mind’.
  2. It is not a rare condition.
  3. I live in constant pain
  4. It’s really hard being this sick for so many years without receiving any medication that will fix the problem.
  5. I lost all my independence when I was 15 years old.
  6. I spend most of my time living in a world of one room
  7. M.E. puts a huge strain on any family setup because everyone’s life has to revolve around the disease.
  8. I divide my day up into family time, rest time, and helping run my charity (Share a Star) from my bed.
  9. When you are chronically unwell, you really start to have to appreciate the little things in life.
  10. I’m bedridden activist
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Intracranial compliance is associated with symptoms of orthostatic intolerance in CFS

Research abstract:

Intracranial compliance is associated with symptoms of orthostatic intolerance in chronic fatigue syndrome, by Andreas Finkelmeyer, Jiabao He, Laura Maclachlan, Andrew M Blamire, Julia L Newton in PLoS One. 2018 Jul 3;13(7):e0200068

Symptoms of orthostatic intolerance (OI) are common in Chronic Fatigue Syndrome (CFS) and similar disorders. These symptoms may relate to individual differences in intracranial compliance and cerebral blood perfusion. The present study used phase-contrast, quantitative flow magnetic resonance imaging (MRI) to determine intracranial compliance based on arterial inflow, venous outflow and cerebrospinal fluid flow along the spinal canal into and out of the cranial cavity.

Flow-sensitive Alternating Inversion Recovery (FAIR) Arterial Spin Labelling was used to measure cerebral blood perfusion at rest. Forty patients with CFS and 10 age and gender matched controls were scanned.

Severity of symptoms of OI was determined from self-report using the Autonomic Symptom Profile. CFS patients reported significantly higher levels of OI (p < .001). Within the patient group, higher severity of OI symptoms were associated with lower intracranial compliance (r = -.346, p = .033) and higher resting perfusion (r = .337, p = .038). In both groups intracranial compliance was negatively correlated with cerebral perfusion.

There were no significant differences between the groups in intracranial compliance or perfusion. In patients with CFS, low intracranial compliance and high resting cerebral perfusion appear to be associated with an increased severity of symptoms of OI. This may signify alterations in the ability of the cerebral vasculature to cope with changes to systemic blood pressure due to orthostatic stress, but this may not be specific to CFS.

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