CFS/ME diagnosis in Norway

Posted on 02/15/2016 by wames

Research abstract:

BACKGROUND

Chronic fatigue is a frequently occurring problem in both the primary and specialist health services. The Department of Neurology at Haukeland University Hospital has established a standard assessment for patients referred with suspected CFS/ME. This study reports diagnoses and findings upon assessment, and considers the benefit of supplementary examinations.

MATERIAL AND METHOD

Diagnoses and findings from examinations of 365 patients assessed for suspected CFS/ME are retrospectively reported.

RESULTS

A total of 48 patients (13.2 %) were diagnosed with CFS/ME, while a further 18 patients (4.9 %) were diagnosed with post-infectious fatigue. Mental and behavioural disorders were diagnosed in 169 patients (46.3 %), and these represented by far the largest group. Serious, but unrecognised somatic illness was discovered in two patients, while changes of uncertain significance were identified by MRI and lumbar puncture in a few patients.

INTERPRETATION

Fatigue is a frequently occurring symptom in the population. Thorough somatic and psychiatric investigation is necessary before referral to the specialist health services. Mental disorders and reactions to life crises are common and important differential diagnoses for CFS/ME. Long waiting times in the specialist health services may result in delayed diagnosis for these patients.

Investigation of suspected chronic fatigue syndrome/myalgic encephalopathy, by J F Owe, H Næss, I O Gjerde, J E Bødtker,　O-B Tysnes  in Tidsskr Nor Legeforen Nr. 3 – 9. februar 2016; 136:227 – 32

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Genetic variations found in ME/CFS

Posted on 02/15/2016 by wames

Research abstract:

Myalgic encephalomyelitis, also known as chronic fatigue syndrome or ME/CFS, is a multifactorial and debilitating disease that has an impact on over 4 million people in the United States alone.

The pathogenesis of ME/CFS remains largely unknown; however, a genetic predisposition has been suggested.

In the present study, we used a DNA single-nucleotide  polymorphism (SNP) chip representing over 9 06 600 known SNPs to analyze DNA from ME/CFS subjects and healthy controls.

To the best of our knowledge, this study represents the most comprehensive genome-wide association study (GWAS) of an ME/CFS cohort conducted to date.

Here 442 SNPs were identified as candidates for association with ME/CFS (adjusted P-valueo0.05). Whereas the majority of these SNPs are represented in non-coding regions of the genome, 12 SNPs were identified in the coding region of their respective gene.

Among these, two candidate SNPs resulted in missense substitutions, one in a pattern recognition receptor and the other in an uncharacterized coiled-coil domain-containing
protein.

We also identified five SNPs that cluster in the non-coding regions of T-cell receptor loci.

Further examination of these polymorphisms may help identify contributing factors to the pathophysiology of ME/CFS, as well as categorize potential targets for medical intervention strategies.

INTRODUCTION

Myalgic encephalomyelitis, also known as chronic fatigue syndrome or ME/CFS, is a complex and heterogeneous disease that has a severe impact on the health and quality of life of those afflicted.

Current estimates suggest that as many as 2.5% of adults may suffer from ME/CFS.1,2

The etiology of ME/CFS is currently unknown; however, it is often characterized by neurological symptoms, memory and concentration impairment, viral reactivation and sleep abnormalities.3

Inflammatory sequelae and innate immune dysregulation are also commonly reported and include increased proinflammatory cytokine expression and decreased natural killer cell function and numbers, potentially leading to increased susceptibility to infection.4–6

In addition, ME/CFS cases often present with gastrointestinal abnormalities, which are commonly misdiagnosed initially as irritable bowel syndrome.7–11

Currently, there is no pathognomonic biomarker or clinical diagnostic test that can definitively delineate ME/CFS; therefore, diagnosis is mainly based on clinical observation and medical anamnesis with subjects meeting defined inclusion and exclusion criteria.12,13

Several lines of evidence support the possibility that ME/CFS development may involve a heritable component. Albright et al.14 conducted familial clustering analysis and reported
significantly higher risk for ME/CFS for first-degree relatives.

In addition, studies of monozygotic and dizygotic twins suggest that there is a higher rate of fatigue concordance in monozygotic twins when compared with dizygotic twins.15,16

The expression of major histocompatibility complex class II antigens HLA-DQA1*01 and HLA-DR4 has also been suggested as a potential risk factor in developing ME/CFS.17,18

Moreover, single-nucleotide polymorphisms (SNPs) in the tumor necrosis factor-a and interferon-y genes may implicate genetic factors in the dysregulation of inflammatory cytokine production.19

In recent years, genome-wide association studies (GWAS) have brought exciting new insights into the genetic underpinnings of many complex diseases.

Polymorphisms have been identified in genes coding for proteins implicated in the disease processes of multiple sclerosis,20 systemic lupus erythematosus21 and Alzheimer’s disease.22

In addition, GWAS have proven to be instrumental in identifying genes with complex interactions.23–25

Current SNP arrays allow for the concurrent screening of approximately one million known human SNPs, a capacity that has contributed notably to our knowledge of genetic influences on disease pathology.26

Previous to this study, only one single large (41 00 000 SNPs) GWAS has been conducted to address the pathophysiology of ME/CFS.27

Smith et al. genotyped 40 ME/CFS subjects meeting the 1994  Fukuda et al. criteria13 and 40 controls with 1 16 204 known SNPs.

Three polymorphisms of interest were highlighted: two SNPs in GRIK2, a gene implicated in a number of neurological maladies such as autism and schizophrenia and an SNP within the NPAS2 gene, which is a putative circadian clock gene.

By screening ME/CFS cases and controls, we identified 442 candidate SNPs that associated with the disease cohort with statistical significance.

Our pilot study supports the previous observations of other genetic screening studies and extends these results by identifying additional potential candidate polymorphisms.

Genome-wide association analysis identifies genetic variations in subjects with myalgic encephalomyelitis/chronic fatigue syndrome, by KA Schlauch, SF Khaiboullina, KL De Meirleir, S Rawat, J Petereit, AA Rizvanov, N Blatt, T Mijatovic, D Kulick, A Palotás and VC Lombardi in Translational Psychiatry (2016) 6, e730  [published online 9 Feb 2016]
 

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Is facebook helpful for people with CFS/ME?

Posted on 02/15/2016 by wames

Phd thesis abstract:

This portfolio thesis comprises of three parts.

The first part is a systematic literature review, in which empirical literature relating to the use of Facebook groups in health conditions is explored. It aims to provide an understanding of how individuals with health conditions use Facebook groups. The review concludes with recommendations for future research.

Part two is an empirical report of a study that used a qualitative approach of content analysis to explore the use of Facebook groups by those with a diagnosis of Chronic Fatigue Syndrome (CFS), also known as Myalgic Encephalomyelitis (M.E.). Participants completed an online survey and data was extracted from a single Facebook group. Results were considered in relation to the Shifting Perspectives Model of Chronic Illness (Paterson, 2001). Methodological limitations, potential clinical implications and areas of future research are also identified.

Part three comprises the appendices and reflective statement. These include a statement reflecting on the research process and supplementary information pertaining to the literature review and empirical study.

6.2. Discussion
Given that CFS/ME online forums have more than ten times the relative activity of any  other disorder or condition related forum, and the concerns around whether this affected  their symptoms (Knudsen et al., 2012), this study aimed to explore the function Facebook groups serve in relation to the Shifting Perspectives Model of Chronic Illness (Paterson, 2001) and the experience of those who use them.

The results highlighted aspects of Facebook groups which were considered to be helpful  and not so helpful. The accessibility of Facebook was considered as both a positive and a negative, due to its easy access and the resulting reduction in social isolation, however  concerns were raised around the inability to avoid distressing posts. The accessibility of  Facebook is a factor which may result in differences between other online forums and the Facebook groups. It is considered that this may result in Facebook being more active than other forums, and may also result in the perception of a more intimate network of support due to the likelihood of most individuals utilising the group inadvertently sharing information about themselves through their profile (dependent on their own privacy settings).

Support, of both an emotional and practical nature was considered to be helpful in the  groups in varying forms, with participants being positive about their experience in the  groups.

The group dynamics, content of posts, and the impact using Facebook could have on ‘real life’ were considered to be factors which were not so helpful about Facebook.

The analysis of the Facebook posts identified that the most prevalent type of posts were
individuals sharing experiences or asking for advice. The concept of sharing experiences was considered further and entailed individuals relating symptoms, updating the group and sharing their frustrations with having the condition.

The content of the posts could be considered to be of a nature which would increase
symptoms, as may be expected by the health anxiety model (Salkovskis & Warwick, 1986), and may be considered to result in individuals focusing on illness. Given the unknown aetiology, the stigma of CFS/ME and the Shifting Perspectives Model of Chronic Illness (Paterson, 2001) however, it was considered that these posts may serve a more positive function.

In relation to the consideration of the Shifting Perspectives Model of Chronic Illness
(Paterson, 2001), it could be suggested that Facebook groups serve a function to gain the wellness perspective. Paterson (2001) suggested that individuals gain the wellness  perspective through education about their illness, being in supportive environments,
identifying their own limits and body responses and sharing their knowledge and  experiences with others, and the findings of this study suggest that the Facebook groups  are used for this purpose. It may be however, that due to the lack of understanding  around the aetiology and treatments of the condition, and the conflicts these can cause
within the Facebook groups, there may be a risk of perspective being one of illness.

The majority of respondents to the survey felt the Facebook group helped them focus on
being well, despite posts appearing to focus on the illness, or seemed to recognise the
potential of their perspective to fluctuate depending on group content.

A thematic analysis of the Facebook posts identified four main themes which highlighted the experiences of those individuals with CFS/ME and may provide insight into what Facebook groups provide for these individuals; a space to share feeling overwhelmed and misunderstood and to receive an develop a sense of hope and understanding in relation to the condition. A consideration of this may provide professionals with an insight into the areas where individuals with CFS/ME may require additional support.

Furthermore, it has been identified that a perceived lack of skill to manage the illness,
stigma, and interactions which accentuate feelings of hopelessness or dependency, may
threaten a shift from WitF to IitF, however little evidence has been found to suggest the
Facebook groups result in these threats, rather they provide an arena to support
prevention of this.

The group considered was highly monitored, with posts which may have caused distress  or offence to other members being deleted and those involved being removed from the  group. This may be an example of the online C effect (Suler, 2004) whereby people may act in ways they would not in real life. Results from the survey suggest that this is not an uncommon experience. Therefore whilst the potential risk of these posts is diminished in this group, it may not be the case in others.

Furthermore, given the offensive responses received by the researcher within the survey, it may be that online disinhibition effect (Suler, 2004) is something which needs consideration in relation to the impact of individuals who are targeted within these groups.

Additional Observations
Whilst the research was considered positively by the majority of individuals in the  facebook groups for CFS/ME, a number of individuals raised their concerns that Psychiatry and Psychology were considering their condition, with participants responding to the survey; “Would you do a similar analysis of support groups for diabetes, HIV, MS, lupus? Or is it because you think CFS/ME is in our heads?”

Research has been completed on conditions such as Diabetes (Greene, Choudhry,
Kilabuk & Shrank, 2010; Zhang, He & Sang, 2012), although these have only been
observational in nature and not included participants. The inclusion of participants
however has been a recommendation by a number of studies which have considered the  use of Facebook groups for health conditions (Ahmed, Sullivan, Schneiders & McCrory, 2010; Niwa & Mandrusiak, 2012; Zhang, He & Sang, 2012).

Throughout the study there was a strong theme around a lack of support from, and trust towards, professionals, particularly the psychology and psychiatry professions. As this was not the focus of this particular study it has received little attention, however future
exploration around this may be of benefit to professionals working to support those with
CFS/ME.

Limitations
A limitation of this study, and potentially for future research when advertising on groups within Facebook, is the rate at which the post advert was quickly replaced with newer posts and a systematic approach to ‘boosting’ the post to be prominent in the group was not in place. As a result, despite being advertised for a 2 month period, it may only have been visible to the group members for a few days at a time.

The analysis of the online survey was completed on the full data set, rather than for each
individual survey response. It may be that treating each survey response as an interview, using an Interpretive Phenomenological Analysis approach (Smith, Flowers & Larkin, 2009) would have provided further understanding and the data may be reanalysed at a later date to consider this.

The Shifting Perspectives Model of Chronic Illness (Paterson, 2001) felt appropriate for
use within the study, however, as a model this may need further development as the
process of identifying the perspectives was unclear and greatly interpreted by the researcher. Furthermore, due to the emotive responses, and lack of understanding of the
model by those who completed the survey, some answers were difficult to analyse. Further consideration may need to be given to making the model more accessible to those partaking in research around this area.

It may be considered a limitation that the survey was completed online rather than in person as an interview, as this results in a loss of understanding which one might attain
from body language or intonations, however, given the theory of online disinhibition effect (Suler, 2004), the survey, which also provided anonymity, may have provided the participants with the arena to speak more openly and truthfully.

As previously highlighted, the online survey evoked some offensive responses from
participants which have provided an insight into the emotions some individuals with  CFS/ME hold and may be of interest in relation to engaging this population.

Conclusions
The results of this study suggest that Facebook groups for CFS/ME have some potential
risks associated with them, however these may not be of any greater concern than those
posed to a member of any Facebook group. Rather, the Facebook groups seem to provide individuals with a perspective of wellness in the foreground by providing a shared experience and understanding which, potentially due to the current unexplained cause of the condition, is considered to be lacking in the ’real world’.

An exploration into the use of Facebook groups for health conditions, by Gerri Elizabeth Moxon, University of Hull Phd thesis, 27 Aug 2015

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Does CFS have a neurological origin?

Posted on 02/12/2016 by wames

Review abstract:

Chronic Fatigue Syndrome (CFS) is distinguished by a persistent malaise and lethargy that physical or mental exertion exacerbates for a period of several days. Sufferers can identify a clear-cut beginning to their condition. In many, it follows a viral infection such as glandular fever. Sufferers also experience cognitive difficulties and, sometimes, autonomic disturbances such as dizziness on standing, gastrointestinal upsets, cardiovascular irregularities and immune system dysfunction.

Does chronic fatigue syndrome have a neurological origin?, by Leighton R Barnden in Australasian Science, Volume 36 Issue 8 (Oct 2015) [only abstract available]

Link to a review article by the same author:

Evidence in chronic fatigue syndrome for severity-dependent upregulation of prefrontal myelination that is independent of anxiety and depression, by Leighton R Barnden et al

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3 more UK doctors join request for independent inquiry into PACE Trial

Posted on 02/12/2016 by wames

Dr Charles Shepherd, Dr Nigel Speight, and infectious diseases consultant Dr William Weir have joined 39 other signatories to the open letter to the Lancet which first appeared on Prof Vincent Rancaniello’s ‘Virology’ blog on November 13 2015.

The letter was re-published on 10th November with a comment from Prof Rancaniello:

“On November 13th, five colleagues and I released an open letter to The Lancet and editor Richard Horton about the PACE trial, which the journal published in 2011. The study’s reported findings –that cognitive behavior therapy and graded exercise therapy are effective treatments for chronic fatigue syndrome –have had enormous influence on clinical guidelines for the illness.

“Last October, Virology Blog published David Tuller’s investigative report on the PACE study’s indefensible methodological lapses. Citing these problems, we noted in the letter that “such flaws have no place in published research” and urged Dr. Horton to commission a fully independent review.

“Although Dr. Horton’s office e-mailed that he would respond to our letter when he returned from “traveling,” it has now been almost three months. Dr. Horton has remained silent on the issue. Today, therefore, we are reposting the open letter and resending it to The Lancet and Dr. Horton, with the names of three dozen more leading scientists and clinicians, most of them well-known experts in the ME/CFS field.

“We still hope and expect that Dr. Horton will address – rather than continue to ignore – these critical concerns about the PACE study.”

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Patients’ thoughts about the PACE trial

Posted on 02/12/2016 by wames

Flat Earth and PACE – both on the wrong side of science

PACE and geocentrism – both on the wrong side of science

Why the PACE researchers and their institutions affectation of concern for
participants is particularly sickening hypocrisy

My thoughts about the PACE trial

Tackling fears about exercise is important for ME treatment, analysis indicates [Update 1 – Tom Kindlon has written an excellent BMJ rapid response on the objective vs subjective measures with reference to a subsequent mediation analysis of the PACE trial results. Well worth a read.]

ME isn’t just ‘exercise phobia’: it’s a physical illness [Tanya Marlow, describes life with ME for those living with ME. Reading this, you can understand why patients can get frustrated or angry.]

Telling It Like It Is [Extract: The reason why ME patients react so badly to the researchers who try to impose treatments such as GET and CBT, which are normally associated with mental health conditions, is not because they have a problem with such conditions. It is because they are inappropriate for ME. Because the research which purports to prove their efficacy is riddled with flaws, many of which by themselves would be enough to invalidate the research. Taken together, these flaws should be sufficient to reduce the research to ridicule. Only the high professional standing of the researchers involved serves to stave off such derision and maintain the illusion of ‘excellent science’, just like the fabled Emperor who managed to pass off his nakedness as a fabulous suit of clothes. The use of GET and CBT for ME is based on the idea that people with ME have nothing physically wrong with them but are simply suffering from an unhelpful illusion of illness which keeps them locked in a cycle of inactivity and deconditioning. All they have to do to get out of this, so the story goes, is to let go of this illusion and slowly increase their level of activity until the deconditioning is overcome. The objection which people with ME have to this is nothing to do with a fear of the stigma of mental health. It’s because it simply isn’t true. There is ample evidence that people with ME do have something physically wrong with their bodies – and the experience of many patients who are persuaded to try GET is that far from overcoming the condition it makes them very much worse, sometimes permanently so. Their objection is not one of ‘irrationality’ but quite the opposite: it is a rational objection to a simplistic unproven hypothesis.]

“Is it About Getting Better or NOT Getting Worse?”

 

 

 

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Replacing ME and CFS with SEID is not the way forward

Posted on 02/11/2016 by wames

Abstract of discussion paper:

Myalgic encephalomyelitis (ME), described in the medical literature since 1938, is characterized by distinctive muscular symptoms, neurological symptoms, and signs of circulatory impairment. The only mandatory feature of chronic fatigue syndrome (CFS), introduced in 1988 and redefined in 1994, is chronic fatigue, which should be accompanied by at least four or more out of eight “additional” symptoms.

The use of the abstract, polythetic criteria of CFS, which define a heterogeneous patient population, and self-report has hampered both scientific progress and accurate diagnosis. To resolve the “diagnostic impasse” the Institute of Medicine proposes that a new clinical entity, systemic exercise intolerance disease (SEID), should replace the clinical entities ME and CFS.

However, adopting SEID and its defining symptoms, does not resolve methodological and diagnostic issues. Firstly, a new diagnostic entity cannot replace two distinct, partially overlapping, clinical entities such as ME and CFS.

Secondly, due to the nature of the diagnostic criteria, the employment of self-report, and the lack of criteria to exclude patients with other conditions, the SEID criteria seem to select an even more heterogeneous patient population, causing additional diagnostic confusion. This article discusses methodological and diagnostic issues related to SEID and proposes a methodological solution for the current “diagnostic impasse”.

Replacing Myalgic Encephalomyelitis and Chronic Fatigue Syndrome with Systemic Exercise Intolerance Disease Is Not the Way forward, by Frank N.M. Twisk, in Diagnostics 2016, 6(1), 10 [ME-de-patiënten Foundation, Zonnedauw 15, 1906 HB Limmen, The Netherlands]

Download pdf of full text

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Biomarker research partnerships advocated by Dr Alan Light in video lecture

Posted on 02/10/2016 by wames

Partnerships to Accelerate Biomarker and Mechanisms Discovery in ME/CFS and Fibromyalgia, by Alan Light, Phd
Bateman Horne Center,  Published on Dec 5, 2015

In this live stream education meeting, originally airing on December 2, 2015, Dr Alan Light shared some recent auto-antibody results done in collaboration with top scientists and Dr. Lucinda Bateman, leading ME/CFS clinician and Founder and Chief Medical Officer of the Bateman Horne Center.

 

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London NHS trust finds higher risk of suicide in CFS patients

Posted on 02/10/2016 by wames

Research summary:

Background:

Mortality associated with chronic fatigue syndrome is uncertain. We investigated mortality in individuals diagnosed with chronic fatigue syndrome in secondary and tertiary care using data from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLaM BRC) Clinical Record Interactive Search (CRIS) register.

Methods

We calculated standardised mortality ratios (SMRs) for all-cause, suicide-specific, and cancer-specific mortality for a 7-year observation period using the number of deaths observed in SLaM records compared with age-specific and sex-specific mortality statistics for England and Wales. Study participants were included if they had had contact with the chronic fatigue service (referral, discharge, or case note entry) and received a diagnosis of chronic fatigue syndrome.

Findings

We identified 2147 cases of chronic fatigue syndrome from CRIS and 17 deaths from Jan 1, 2007, to Dec 31, 2013. 1533 patients were women of whom 11 died, and 614 were men of whom six died. There was no significant difference in age-standardised and sex-standardised mortality ratios (SMRs) for all-cause mortality (SMR 1·14, 95% CI 0·65–1·85; p=0·67) or cancer-specific mortality (1·39, 0·60–2·73; p=0·45) in patients with chronic fatigue syndrome when compared with the general population in England and Wales. This remained the case when deaths from suicide were removed from the analysis. There was a significant increase in suicide-specific mortality (SMR 6·85, 95% CI 2·22–15·98; p=0·002).

Interpretation

We did not note increased all-cause mortality in people with chronic fatigue syndrome, but our findings show a substantial increase in mortality from suicide. This highlights the need for clinicians to be aware of the increased risk of completed suicide and to assess suicidality adequately in patients with chronic fatigue syndrome.

Mortality of people with chronic fatigue syndrome: a retrospective cohort study in England and Wales from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLaM BRC) Clinical Record Interactive Search (CRIS) Register, by  Dr Emmert Roberts, MRCP Prof Simon Wessely, FMedSci, Prof Trudie Chalder, PhD, Dr Chin-Kuo Chang in Lancet [Published Online 9 February 2016]

Published comment: Suicide risk in people with chronic fatigue syndrome, by Nav Kapur, Roger Webb [Published online 9 February 2016]

…The results of the current study are potentially very important but need to be interpreted with caution. The study was quite small for an investigation of mortality (n=2147 patients of whom 17 died)…

Daily Mail article by Ben Spencer, 10 February 2016: How the hell of chronic fatigue drives sufferers to suicide: Those battling condition are SIX times more likely to take
their own lives

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Assessment of CBT for CFS in Britons with diverse ethnic backgrounds

Posted on 02/10/2016 by wames

Research abstract:

Background:
Cognitive-behavioural therapy (CBT) is one of the most promising treatments for chronic fatigue syndrome (CFS). It is unclear whether CBT is effective for Black and minority ethnic (BME) groups.

Aims
To assess the effectiveness of CBT in BME patients compared with White British patients presenting to a specialist CFS service.

Method
Data from 67 (19.0%) BME participants and 285 (81.0%) White British participants referred to a specialist CFS service in the UK were collected at baseline and after CBT treatment.

Results
Pairwise comparisons revealed that both BME participants and White British participants significantly improved on measures of fatigue severity (P<0.001), physical functioning (P<0.001) and work/social adjustment (P<0.001). Independent samples t-tests showed that BME participants improved despite exhibiting significantly higher baseline
damage beliefs (P=0.009), catastrophising (P = 0.024), all-or-nothing behaviour (P=0.036) and avoidance/resting behaviour (P=0.001), compared with White British participants.

Conclusions
To our knowledge, this study is the first to indicate that CBT is effective for treating CFS in a group of patients from diverse BME backgrounds.

Chronic fatigue syndrome: comparing outcomes in White British and Black and minority ethnic patients after cognitive-behavioural therapy, by Tom Ingman, Sheila Ali, Kamaldeep Bhui, Trudie Chalder in The British Journal of Psychiatry, February 4, 2016 [Preprint]

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