Re-analysis of genetic risks for CFS from 23andMe data finds few remain

Posted on 04/21/2021 by wames

Re-analysis of genetic risks for Chronic Fatigue Syndrome from 23andMe data finds few remain, by Felice L Bedford, Bastian Greshake Tzovaras in medRxiv 2020.10.27.20220939  [doi.org/10.1101/2020.10.27.20220939]

Data from 23andMe had been compared with a control database that was found to contain errors. A re-analysis found only 3 of 50 previously reportedly significant SNPs survived initial study criterion of at least twice as prevalent in patients. The authors conclude that 23andMe data can be useful but only ‘if caution is taken with chips and SNPs. [s4ME]

 

Research abstract:

SNP model by David Eccles, Wiki commons

It is tempting to mine the abundance of DNA data that is now available from direct-to-consumer genetic tests, but this approach has its pitfalls A recent study put forth a list of 50 single nucleotide polymorphisms (SNPs) that predispose to Chronic Fatigue Syndrome (CFS), a potentially major advance in understanding this still mysterious disease. However, only the patient cohort data came from a commercial company (23andMe) while the control was a genetic database.

The extent to which 23andMe data agree with genetic reference databases is unknown. We reanalyzed the 50 purported CFS SNPs by comparing to control data from 23andMe which are available through public platform OpenSNP. In addition, large high-quality database ALFA was used as an additional control. The analysis lead to dramatic change with the top of the leaderboard for CFS risk reduced and reversed from an astronomical 129,000 times to 0.8.

Errors were found both within 23andMe data and the original study-reported Kaviar database control. Only 3 of 50 SNPs survived initial study criterion of at least twice as prevalent in patients, EFCAB4B involving calcium ion channel, LINC01171, and MORN2 genes. We conclude the reported top-50 deleterious polymorphisms for Chronic Fatigue Syndrome were more likely the top-50 errors in the 23andMe and Kaviar databases.

In general, however, correlation of 23andMe control with ALFA was a respectable 0.93, suggesting an overall usefulness of 23andMe results for research purposes but only if caution is taken with chips and SNPs.

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How peptic ulcer disease could potentially lead to the lifelong, debilitating effects of CFS

Posted on 04/21/2021 by wames

How peptic ulcer disease could potentially lead to the lifelong, debilitating effects of chronic fatigue syndrome: an insight, by Chien-Feng Kuo, Leiyu Shi, Cheng-Li Lin, Wei-Cheng Yao, Hsiang-Ting Chen, Chon-Fu Lio, Yu-Ting Tina Wang, Ching-Huang Su, Nai-Wei Hsu & Shin-Yi Tsai in Scientific Reports vol 11, no.: 7520 (April 2021)

 

Research abstract: 

Chronic Fatigue Syndrome (CFS) has been defined as unexplained relapsing or persistent fatigue for at least 6 consecutive months. Immuno-inflammatory pathway, bacterial infection, and other causes play essential roles in CFS.

Helicobacter pylori infection is one of the most common causes of foregut inflammation, leading to peptic ulcer disease (PUD). This study aimed to analyze the risk of CFS development between patients with and without PUD. Other related factors were also analyzed.

We performed a retrospective, nationwide cohort study identifying patients with or without PUD respectively by analyzing the Longitudinal Health Insurance Database 2000 (LHID2000), Taiwan.

The overall incidence of CFS was higher in the PUD cohort than in the non- PUD cohort (HR = 2.01, 95% CI = 1.75–2.30), with the same adjusted HR (aHR) when adjusting for age, sex, and comorbidities. The sex-specific PUD cohort to the non-PUD cohort relative risk of CFS was significant in both genders. The age-specific incidence of CFS showed incidence density increasing with age in both cohorts. There is an increased risk of developing CFS following PUD, especially in females and the aging population. Hopefully, these findings can prevent common infections from progressing to debilitating, chronic conditions such as CFS.

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Introducing WAMES volunteers: Sharon Williams

Posted on 04/19/2021 by wames

The second in a series introducing WAMES volunteers: the Volunteer Coordinator 

 

Hi! My name is Sharon Williams.

Sharon 2021

I have been involved with WAMES for many years, initially helping to raise awareness and fundraising, but now as Volunteer Coordinator and Volunteer Support Officer, meaning that I recruit, induct and support volunteers. I can’t wait to welcome more people to the team!

My role is key because we need more volunteers with varied skills as we seek to expand and help more people with ME throughout Wales.

This mission is important to me on a personal level. Until the age of 17, I was a healthy and active young person. I was an A grade student and represented Wales at gymnastics.

Then, out of the blue, I got Glandular Fever. After the fever went, I was left with profound fatigue and I was eventually diagnosed with Post Viral Fatigue Syndrome and ME. I was very ill for 20 years but in recent years my symptoms have lessened.

WAMES has helped me in the past so it is nice to give back as a volunteer and turn a negative into a positive.

I am a self-employed French and German teacher and translator. I am married and live in Pembrokeshire, enjoy walking in beautiful landscapes, swimming, knitting and spending time with my friends and family and updating my cat’s Twitter account!

Jan: the chair

Michelle

Mia

Tony

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US ME/CFS clinician coalition recommendations for ME/CFS testing & treatment

Posted on 04/19/2021 by wames

US ME/CFS Clinician Coalition Recommendations for ME/CFS Testing and Treatment, April 13, 2021

 

In its July 2020 handout on ME/CFS diagnosis and treatment, the US ME/CFS Clinician Coalition summarized the alternative diagnoses and comorbidities that need to be evaluated during the differential diagnosis for ME/CFS and also recommended treatment of ME/CFS symptoms and common comorbidities.

The Coalition has now released consensus recommendations for medical providers that include more specifics on the tests and treatments used in caring for people with ME/CFS. The ME/CFS testing recommendations include those tests used to identify alternative diagnoses and comorbidities along with tests to further characterize ME/CFS and to help document disability and guide treatment. These recommendations include a limited set of tests for all patients and additional tests to be ordered based on the patient’s particular presentation. These recommendations are intended as general guidance for a diagnostic process that may extend over several office visits and involve referrals to specialists. The clinician will need to apply their own clinical judgment in deciding which tests to order and whether to refer to a specialist.

The ME/CFS treatment recommendations include pharmacological and non-pharmacological treatments broken down by various aspects of ME/CFS such as orthostatic intolerance, sleep and cognitive impairment, pain, and immune impairment. Comorbidities should be treated using the published standard of care and are not included here. While there is no cure for ME/CFS, treating a patient’s symptoms and comorbidities can help reduce the symptom burden and improve a patient’s quality of life.

These treatment recommendations are intended as general guidance for medical providers and are not a substitute for clinical care by a physician. In deciding on the specific treatment approach, the treating physician should consider the presentation and needs of the individual patient along with up-to-date drug product information for approved uses, dosages, and risks of specific treatments for specific indications. Some people with ME/CFS may have a heightened sensitivity to medications. For these patients, drugs should be started at low doses and increased slowly to avoid triggering drug sensitivities common in ME/CFS.

These recommendations along with additional information on diagnosis and management are available on the US ME/CFS Clinician Coalition website. This Coalition overview is a useful place to start. Medical providers can reach the Coalition at
https://mecfscliniciancoalition.org/contact/

Download the pdf

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Hughes & Tuller challenge study into CBT in a UK specialist CFS clinic

Posted on 04/19/2021 by wames

Response to Adamson et al. (2020): ‘Cognitive behavioural therapy for chronic fatigue and chronic fatigue syndrome: Outcomes from a specialist clinic in the UK’, by Brian M Hughes and David Tuller in Journal of Health Psychology April 10, 2021 [doi.org/10.1177/13591053211008203]

 

Article abstract:

In a paper published in the Journal of the Royal Society of Medicine, Adamson et al. (2020) interpret data as showing that cognitive behavioural therapy leads to improvement in patients with chronic fatigue syndrome and chronic fatigue. Their research is undermined by several methodological limitations, including: (a) sampling ambiguity; (b) weak measurement; (c) survivor bias; (d) missing data and (e) lack of a control group.

Unacknowledged sample attrition renders statements in the published Abstract misleading with regard to points of fact. That the paper was approved by peer reviewers and editors illustrates how non-rigorous editorial processes contribute to systematic publication bias.

Cognitive behavioural therapy for chronic fatigue and chronic fatigue syndrome: outcomes from a specialist clinic in the UK, by James Adamson , Sheila Ali, Alastair Santhouse, Simon Wessely, Trudie Chalder in Journal of the Royal Society of Medicine, Vol: 113 issue: 10, pp: 394-402, Oct 1 2020 [doi.org/10.1177/0141076820951545]

Research abstract: 

Objectives
Cognitive behavioural therapy is commonly used to treat chronic fatigue syndrome and has been shown to be effective for reducing fatigue and improving physical functioning. Most of the evidence on the effectiveness of cognitive behavioural therapy for chronic fatigue syndrome is from randomised control trials, but there are only a few studies in naturalistic treatment settings. Our aim was to examine the effectiveness of cognitive behavioural therapy for chronic fatigue syndrome in a naturalistic setting and examine what factors, if any, predicted outcome.

Design
Using linear mixed effects analysis, we analysed patients’ self-reported symptomology over the course of treatment and at three-month follow-up. Furthermore, we explored what baseline factors were associated with improvement at follow-up.

Setting
Data were available for 995 patients receiving cognitive behavioural therapy for chronic fatigue syndrome at an outpatient clinic in the UK.

Participants
Participants were referred consecutively to a specialist unit for chronic fatigue or chronic fatigue syndrome.

Main outcome measures
Patients were assessed throughout their treatment using self-report measures including the Chalder Fatigue Scale, 36-item Short Form Health Survey, Hospital Anxiety and Depression Scale and Global Improvement and Satisfaction.

Results
Patients’ fatigue, physical functioning and social adjustment scores significantly improved over the duration of treatment with medium to large effect sizes (|d| = 0.45–0.91). Furthermore, 85% of patients self-reported that they felt an improvement in their fatigue at follow-up and 90% were satisfied with their treatment. None of the regression models convincingly predicted improvement in outcomes with the best model being (R2 = 0.137).

Conclusions
Patients’ fatigue, physical functioning and social adjustment all significantly improved following cognitive behavioural therapy for chronic fatigue syndrome in a naturalistic outpatient setting. These findings support the growing evidence from previous randomised control trials and suggest that cognitive behavioural therapy could be an effective treatment in routine treatment settings.

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Life-threatening malnutrition in very severe ME/CFS

Posted on 04/19/2021 by wames

Life-threatening malnutrition in very severe ME/CFS, by Helen Baxter, Nigel Speight and William Weir in Healthcare 2021, 9(4),  459; [doi.org/10.3390/healthcare9040459] 14 April 2021 (This article belongs to the Special Issue ME/CFS – the Severely and Very Severely Affected)

 

Case Reports abstract:

Very severe Myalgic Encephalomyelitis (ME), (also known as Chronic Fatigue Syndrome) can lead to problems with nutrition and hydration. The reasons can be an inability to swallow, severe gastrointestinal problems tolerating food or the patient being too debilitated to eat and drink.

Some patients with very severe ME will require tube feeding, either enterally or parenterally. There can often be a significant delay in implementing this, due to professional opinion, allowing the patient to become severely malnourished. Healthcare professionals may fail to recognize that the problems are a direct consequence of very severe ME, preferring to postulate psychological theories rather than addressing the primary clinical need.

We present five case reports in which delay in instigating tube feeding led to severe malnutrition of a life-threatening degree. This case study aims to alert healthcare professionals to these realities.

 

Excerpt from Discussion:

This series of cases demonstrate a common set of problems. The clinicians involved seemed unaware that severe ME can lead to serious problems maintaining adequate nutrition and hydration. Perhaps this is understandable, as many clinicians will only meet one or two cases of severe ME in their careers, and the subject is poorly taught at both undergraduate and postgraduate levels…

Case 2 highlights an important issue. If a patient is failing to respond to enteral feeding, the possibility of MCAD needs to be considered. This is a recognized complication of severe ME and effective treatment exists in the form of oral cromoglycate and antihistamines. It has probably contributed to several deaths of severe ME sufferers.

In every case, the most positive improvement in their management came about as the result of the allocation of a named HENS dietician whose advanced training in enteral nutrition enabled them to make changes to the patient’s diet. In one case it enabled the patient to get to a healthy weight using enteral nutrition whilst making changes to the oral nutrition such that enteral feeding is now no longer required. In another case, dietary changes ameliorated suffering. All patients felt supported by their HENS dietician.

For patients with very severe ME connecting with a knowledgeable healthcare professional who does domiciliary visits is very important. Such a policy would reduce the need for hospital admissions which would be to the benefit of all. All patients with very severe ME should be allocated a HENS dietician as soon as nutritional difficulties become apparent.

An early warning system needs to be put in place for patients with severe ME so that when they or their representatives become aware of the development of problems with oral intake prompt action is taken and tube feeding started thereby avoiding undernutrition in patients with very severe ME. Early intervention in the form of tube feeding has been shown to be beneficial in patients with severe ME [1].

Patients with very severe ME are bedridden and require around the clock care. They are best cared for at home where the environment can be adapted to best meet their needs. These patients will have extreme sensitivity to noise and light, such that they need to be cared for in a darkened room. People with very severe ME invariably report travel to hospital and the hospital environment significantly exacerbates their condition. If an admission to hospital is necessary, and this should only be done for emergency treatment, they will require admission directly into a side room and to be cared for by a small number of staff who understand ME as an organic illness.

For the patient with very severe ME, it appears to be common practice for Clinical Commissioning Groups (CCGs) to adopt a ‘re-site in hospital’ policy despite a large study showing that with protocols in place trained nurses in the community can identify the position of NGT’s correctly without the need for hospital attendance [12].
Nonetheless it is stated: ‘Local protocols should address the clinical criteria that permit enteral feeding [13].’

None of the participants were offered NGT re-sites at home, instead they went to significant lengths to avoid trips to hospital if at all possible; re-siting their own NGTs or opting to have NJTs or PEGs. A constructive change would an implementation of national guidelines allowing NGT re-sites to be carried out in the community by appropriately trained professionals. A community-based service could bring potential savings to the NHS and certainly benefit patients with very severe ME. The treatment of serious undernutrition issues in ME needs to be included in national and local guidelines for use by health care professionals.

Summary article from MECENTRAAL

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Introducing WAMES volunteers: Jan Russell

Posted on 04/16/2021 by wames

Introducing WAMES volunteers: Jan Russell

 

The first in a series introducing WAMES volunteers: the Chair  

Back in 2000 I was one of a small band of support group reps who got together to discuss what we could do to improve services for people with ME. I had been active in the Mid & West Wales Support Group for many years.  Devolution had just removed control for most services from London to Cardiff, and ME wasn’t on the new government’s horizon. WAMES was established in 2001 and I became the volunteer Treasurer.

Jan Russell with long lockdown hair

Jan with lockdown hair, 2021

It very quickly became clear that book keeping was not my forte so the following year I gladly exchanged roles with the Secretary!  Finally 9 years ago I became chair. That was not an easy decision to make as I wasn’t sure I was well enough. However, I was motivated, having developed ME following 2 bouts of post viral debility in the mid 80s and I was very frustrated, even angry, that recognition and services were not improving.

Working as part of a team who understands ME is the most stress-free way to make a useful contribution, though I have to admit to having to operate outside my comfort zone on occasion. My husband (and carer) has made that possible and has provided important support!  As well being a trustee and chair (leading meetings and planning WAMES activities) I have also led the health services campaign, and got involved with the website, magazine, facebook… (the list goes on!).

There is so much work I could be doing with WAMES but I have found it important to develop other interests as well, to keep a balance in my life. Many of these activities had to replace the pastimes I could no longer do once I became ill and I now enjoy genealogy, pottering in the garden (on better days), wildlife watching (often from my house window) and reading crime novels.

Jan speaking at the Senedd, 2018

Looking back I can see how much I have learned and the new skills I have developed while volunteering. Before I became ill I was a librarian working first in schools in Scotland and then in Aberystwyth university. Making information available to people is second nature to me and I have enjoyed helping WAMES provide information and support to many families to help them access what few services are available.

l wish I could say I could also see how successful WAMES has been in influencing service improvement. That has been a painfully slow process, like water dripping on a stone. But I am relieved to say I can see an improvement in recognition and understanding of ME in Wales. I am sure the breakthrough is just round the corner and I am proud to have played a part in edging us towards that!

Read other volunteers’ stories:

Michelle

Sharon

Mia

Tony

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Insights into metabolite diagnostic biomarkers for ME/CFS

Posted on 04/13/2021 by wames

Insights into metabolite diagnostic biomarkers for Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome, by Emi Yamano, Yasuyoshi Watanabe and Yosky Kataoka in Int. J. Mol. Sci. 2021, 22(7), 3423; [doi.org/10.3390/ijms22073423] 26 March 2021
(This article belongs to the Special Issue Environmental Sensitivity Illnesses: Mechanisms and Molecular Signatures 2.0)

 

Review abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a persistent and unexplained pathological state characterized by exertional and severely debilitating fatigue, with/without infectious or neuropsychiatric symptoms, and with a minimum duration of 6 consecutive months.

Its pathogenesis is not fully understood. There are no firmly established diagnostic biomarkers or treatment, due to incomplete understanding of the etiology of ME/CFS and diagnostic uncertainty.

Establishing a biomarker for the objective diagnosis is urgently needed to treat a lot of patients. Recently, research on ME/CFS using metabolome analysis methods has been increasing. Here, we overview recent findings concerning the metabolic features in patients with ME/CFS and the animal models which contribute to the development of diagnostic biomarkers for ME/CFS and its treatment. In addition, we discuss future perspectives of studies on ME/CFS.

Table 2. Summary of major biochemical pathways with significant metabolites across patients with ME/CFS:

Table 2. Summary of major biochemical pathways with significant metabolites across patients with ME/CFS.

 

 

 

4. Conclusions
Common metabolic fluctuations were observed in fatigued animal models and human patients with ME/CFS and these findings could contribute to the elucidation of the pathophysiology of ME/CFS. Biomarker research, to distinguish between patients with ME/CFS and healthy individuals, is still evolving.

In previous studies, reactive oxygen metabolite-derived compounds (d-ROMs) [54] in the blood, exosomes and inclusion proteins/micro RNAs [5], monocyte number, and lipoprotein profiles have been reported to be informative markers for discriminating patients with ME/CFS from healthy controls [55]. Furthermore, inflammation and immune system activation have been suggested by many previous studies to be the root causes of ME/CFS, and the results from many such studies have shown elevation of cytokines and lymphokines in plasma [56].

Using positron emission tomography (PET), neuroinflammation was detected in wide-spread brain regions of patients with ME/CFS, which was associated with the severity of the specific neuro-psychologic symptoms [57].

We believe that in future, it will be possible to establish highly precise objective diagnostic biomarkers for ME/CFS, exhibiting diverse pathologies through the implementation of research that would integrate metabolomic markers reflecting the specific metabolism underlying the pathophysiology of fatigue with highly precise in vivo biomarkers.

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WAMES is growing to meet the challenges of 2021

Posted on 04/12/2021 by wames

WAMES is growing to meet the challenges of 2021 – AGM News

 

Our AGM was held virtually on 27th March 2021.   It was a time to take stock of the disruptions of 2020 and discuss how to tackle the challenges of the future for people with ME.

The big ongoing discussion is how we can continue to highlight the desperate need for services as we wait for the publication of the revised NICE guidelines in the midst of a growing group of patients with the overlapping symptoms of long COVID. We will be sharing those activities and requesting your help over the next few months.

 

Our Vision:

Our Vision is for a Wales where adults and children with ME, CFS and PVFS and their carers are taken seriously and treated with respect, where diagnosis, treatment and services are accessible without a battle.

 

Our Volunteers:

We are enjoying getting to know the growing number of volunteers who have been joining us over the last year. They will be critical in helping us to get ME taken more seriously in Wales. We need people with a wide range of skills and interests and are inviting more people to join us.  We work in Teams so we can share tasks and responsibilities, and inspire and encourage each other.

Volunteers are the lifeblood of  WAMES

 

Our Teams:

Trustees & Governance
we set the goals for WAMES and ensure we stay ‘on mission’ in line with charity law.

Administration
we work in the background and provide a framework for everything else to happen – maintaining records, memberships, mailing lists and general admin tasks.

Campaigns & Awareness
we find and respond to opportunities to improve services and spread the word about ME.

Support
we respond to queries and provide support to individuals and groups through the helpline, email, social media etc.

Communications
we look for ways to communicate bilingually about ME and WAMES throughout Wales using the website, social media and ‘pre-Covid’ paper formats.

Volunteering
we recruit, induct and support volunteers to ensure everyone has the best possible experience with WAMES.

Finances & fundraising
we find ways to raise enough money to fund our activities and ensure we plan ahead for the future.

Youth
this team has been less active for a few years but aims to pick up the pace and improve the support and information we give to children and young people.

Elected officers 2021:

  • Chair: Jan Russell
  • Acting secretary: Tony Thompson
  • Treasurer: Simon Horsman

See future blogs to meet our volunteers!

 

Finances:

For the 2nd year running in 2020 we spent more than we received! We received £510 and spent £969. Online shopping fundraising and donations from individuals make up the bulk of our income as people shop more from home, but we also saw a big drop in donations – 53%! We are working to develop a more sustainable way to fund our work as everybody experiences economic challenges.

The bulk of our expenditure in the past has been on travel and accommodation costs to enable us to campaign and raise awareness.  The pandemic has changed this. Instead, during 2021 we will need to invest in office hardware and software to ensure our growing team of volunteers can work effectively together virtually. We have enough money in the bank to make a start on this but will need to fundraise to complete the project.

Did you donate or fundraise by shopping online?
Thanks for the lifeline!

 

WAMES’ aim is to:

give a national voice to people with ME, CFS and PVFS in Wales, their carers and families, in order to improve services, access to services, awareness and support.

Help us…. Make a difference for ME in Wales!

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New study shows reduced ability to regulation of the cardiovascular system in patients with ME/CFS

Posted on 04/08/2021 by wames

Kavli Trust blog post on research into ME / CFS at Haukeland University: New study shows reduced ability to regulate the cardiovascular system in patients with ME / CFS, March 26, 2021     [Google translation of a Norwegian article]

 

The research group for ME / CFS at Haukeland University Hospital has published a new article on possible circulatory disorders in patients with ME/CFS. Examinations of patients’ blood vessels using ultrasound have been an important part of the study, which was carried out with support from the Kavli Foundation.

By the research group for ME / CFS at Haukeland University Hospital:

We performed examinations of the patients’ blood vessels as part of the Cyclophosphamide project on ME / CFS, which was carried out with support from the Kavli Foundation. The group has previously published results showing that 22 of the 40 participants in the study reported improvement in their ME disease after being treated with the cytotoxic drug cyclophosphamide in a controlled clinical trial.

Read more: Promising results from experiments with cancer medicine

This study is based on a hypothesis that impaired ability to regulate blood circulation is a possible disease mechanism in ME / CFS. The ability of the blood vessels to fine-tune the blood flow so that the tissue receives enough oxygen and nutrition, especially during exertion, may be affected. This may contribute to the patients’ symptom picture.

A recognized method for studying the regulation of blood circulation is to examine the function of the patients’ endothelium. This cell layer, which covers the inside of the blood vessels, contributes to the expansion and contraction of the veins as needed. During the examination, the patients’ blood circulation in the right arm is limited by means of a blood pressure cuff for five minutes. When this blockage is removed, the blood vessels should normally compensate by dilating and releasing more blood to the arm…

…At re-examination after 12 months, 55% of the patients had experienced a symptom improvement after treatment with cyclophosphamide. Nevertheless, the results for endothelial function at group level were relatively unchanged, and we found no systematic relationship between change in symptoms and change in endothelial function. Nor could we demonstrate a direct relationship between patients’ endothelial function and their level of activity, the severity of the disease, or how long they had been ill.

This study therefore concludes that there is an association between ME / CFS and reduced endothelial function, but that we can not see any direct correlation between endothelial function and the individual patient’s symptom pressure. Regulation of blood circulation is a complex process, and we still have a lot to learn about circulatory disorders in ME / CFS and how they affect patients’ symptoms.

You can read the study in its entirety at Frontiers in Medicine:

Reduced endothelial function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome–results from open-label Cyclophosphamide intervention study, by Kari Sørland,  Miriam Kristine Sandvik,  Ingrid Gurvin Rekeland,  Lis Ribu,  Milada Cvancarova Småstuen,  Olav Mella and  Øystein Fluge in Front. Med., 22 March 2021 [doi.org/10.3389/fmed.2021.642710]

Read more: Collection page about ME research supported by the Kavli Foundation

Read the full translated article

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