The Power and Pitfalls of Omics: George Davey Smith’s storming talk at ME/CFS conference
Read about the talk that stole the show at a recent ME/CFS conference in Simon McGrath's two-part blog.
Discuss the article on the Forums.

CMRC Conference reports: Patient session, Immunology, MRC studies updates+

Discussion in 'General ME/CFS News' started by Simon, Oct 1, 2014.

  1. Simon

    Simon

    Messages:
    1,914
    Likes:
    14,392
    Monmouth, UK
    UK CFS/M.E. Research Collaborative | CMRC conference report, September 2014 (report organised by Action for ME)

    The UK CFS/ME Research Collaborative (CMRC) is writing a full report of its September 2014 conference, with presentation and workshop summaries being made available as soon as they are ready.

    “We have been working hard with researchers to pull together a report that gives a flavour of the UK CFS/ME Research Collaborative’s first science conference," says Sonya Chowdhury, CEO of Action for M.E. and UK Research Collaborative Executive Board Member.

    "This report has only been made possible thanks to the support of Action for M.E. staff and volunteers, Prof Jonathan Edwards, Dr Charles Shepherd and the researchers themselves. We are nearing completion of the report but because of the level of interest, we are releasing each section as it is completed."

    If you wish to share any part of the report, please provide a link to it here and do not reproduce without express permission from Action for M.E. Please do contact us to discuss this further.

    Plenary session one on inflammation
    (see thread CMRC Conference report: Welcome & plenary session on Inflammation)

    • Welcome by Prof Stephen Holgate, CMRC Chair
    • Anne Faulkner Lecture: The neuroimmune basis of fatigue by Prof Robert Dantzer, University of Texas Anderson Cancer Centre
    • Interferon-alpha rapidly changes brain microstructure by Dr Neil Harrison, University of Sussex
    • Interferon-alpha induced persistent fatigue by Alice Russell, Kings College London
    • Blood cytokine concentrations in CFS: a systematic review by Dr Lisa Blundell, Barts and the London School of Medicine and Dentistry
    • Resveratrol treatment on TNF-α-induced cytokine release by Kate Earl, University of Liverpool
    More to follow
     
    Last edited: Oct 1, 2014
    Sasha, barbc56, Ecoclimber and 3 others like this.
  2. Simon

    Simon

    Messages:
    1,914
    Likes:
    14,392
    Monmouth, UK
    Plenary session two: MRC-funded CFS/ME research

    Understanding the pathogenesis of autonomic dysfunction in CFS and its relationship with cognitive impairment

    Dr Stuart Watson (for Prof Julia Newton), Newcastle University

    Biological fingerprints of fatigue

    Prof Wan-Fai Ng, Newcastle University

    Inflammation and fatigue: is it different from depression?

    Prof Carmine Pariante, King’s College London

    Sleep and CFS/ME

    Dr Sue Wilson (for Prof David Nutt), Imperial College London

    Mitochondrial function and cytokine production in skeletal muscle of patients with CFS/ME

    Prof Anne McArdle, University of Liverpool

    The epidemiology of CFS/ME in adolescence

    Dr Esther Crawley, University of Bristol

    PACE: A trial & tribulations

    Prof Peter White, Barts and the London School of Medicine and Dentistry

    Understanding the pathogenesis of autonomic dysfunction in chronic fatigue syndrome and its relationship with cognitive impairment

    Dr Stuart Watson (for Prof Julia Newton), Newcastle University

    Prof Newton’s team have recruited the same set of patients to take part in a number of studies, which Dr Watson gave an overview of in his presentation, stressing that they had collected only preliminary data for some so far.

    “We have recruited to time and to target, largely because of the community of people with CFS/ME,” he said. “They have knocked on the door, got in touch on Facebook and come forward to take part in this research, which has been fantastic.”

    Studies include dexamethasone suppression of cortisol, showing that glucocorticoid receptors in people with CFS/ME are down-regulated, contradicting previous reports.

    Another looking at immune function found no evidence for an increase in pro-inflammatory cytokines, again contrasting with previous studies.Considering why this might be, Dr Watson explained that they had taken pains to exclude people who had current or past psychological issues. “Clearly there is a link between the HPA axis and depression,” he said.

    “Similarly, we also looked at childhood adversity; previously studies have found high levels of this – abuse, neglect – in people with CFS/ME. But we didn’t; we found the same levels as with healthy controls, because we were very careful to exclude people with existing or historic psychiatric disorders.”

    A further study is investigating whether autonomic nervous system (ANS) dysfunction could be a contributing factor to the pathological processes behind CFS/ME, using a standardised test called valsalva manoeuvre.

    Another investigates cognitive impairment in people with CFS/ME by looking at the links between fatigue, objective task performance and subjective reports of memory.

    Dr Watson also mentioned other relevant studies being undertaken by the team, including mitochondrial genomics, the way muscle cells behave in people with CFS/ME, and subjective experiences of sleep.

    “The headline from the sleep study is that sleep disturbances were highly unpredictable and variable over time, but played a key role in symptom maintenance for people with CFS/ME,” he said.

    Prof Jonathan Edwards comments: “For me the interesting aspect here was the evidence of neuroendocrine imbalance, together with clinical evidence of autonomic disturbance, in the absence of blood cytokine changes. The implication for me is, again, that central nervous signalling pathways can be measurably abnormal without there being any peripheral cytokine evidence.

    “Of note, Dr Watson is a psychiatrist working together with Dr Newton on a wide range of aspects of CFS/ME, and their collaboration seems to be doing much to fit everything together in a unified biological model.”


    Biological fingerprints of fatigue[/B][/B]
    Prof Wan-Fai Ng, Newcastle University

    Prof Ng described his ongoing work on the hypothesis that there are common biological pathways underpinning fatigue.

    Identifying this “biological fingerprint” will, he says, improve our understanding of the underpinning biological basis of fatigue, provide an objective measure to assess the effectiveness of treatments for alleviating fatigue, and aid diagnosis of CFS/ME.

    To do this, Prof Ng is looking at patients with primary Sjogren’s syndrome, some of whom experience high levels of fatigue, while others do not. The study which is using RNA extraction from white blood samples from patients with Sjogren’s Syndrome (SS) – where fatigue can be a very prominent and disabling clinic feature – to see if they can identify any markers in the blood ( biomarkers) that are consistent with people who have SS plus fatigue and are not present in patients with SS who do not have fatigue.

    This research is also looking for changes in gene expression analysis that correlate with fatigue. The work will then progress to see if similar markers are present in people with CFS/ME. Although not related to the MRC funded study, there is a clinical trial of Rituximab taking place in people with Sjogren’s Syndrome in Newcastle.
    Prof Jonathan Edwards comments: “Interestingly Prof Pariante found a pattern of change in gene expression in Sjogren’s patients but this tended to be more marked in those with less fatigue. Sjogren’s patients were drawn from a cohort within which a trial of rituximab is taking place and it is hoped that response to treatment can be correlated with the serological fingerprint.

    “This study emphasised to me the fact that different facets of a single disease may be mediated by different pathways. It rather looks as if fatigue in Sjogren’s syndrome is mediated by pathways that are not involved in the production of other features of the disease.”


    Inflammation and fatigue: is it different from depression?
    Prof Carmine Pariante, King’s College London

    Following on from Alice Russell’s presentation, Prof Pariante explained in more detail the studies he and has team have been conducting looking at the effect of interferon-alpha treatment on fatigue levels in patients with Hepatitis C.

    They have been exploring what happens to various biomarkers when people with chronic hepatitis C infection are treated with interferon alpha (IFN alpha). The aim is to see if there are differences between those who develop fatigue and other CFS/ME like symptoms and those who do not, and what happens where these symptoms persist when treatment has stopped and there viral load is removed. This study is also examining whether there are changes in gene expression between the two groups – which could again provide useful clues as to what may be happening in CFS/ME.

    One of the several interesting findings from the studies on hepatitis C patients being treated with IFN alpha is that the various CFS/ME-like symptoms start to appear at different time intervals. Flu-like feelings occur very quickly; fatigue gradually builds up over a period of several weeks and plateaus. Whereas changes in mood and depression, along with cognitive dysfunction start to appear rather later and again gradually increase in severity before reaching a steady state.

    He went onto look at how depression relates to fatigue, and how our understanding of the former can help us map the letter. He also considered how abnormal inflammation affects brain function, and how we can use it to understand fatigue. One other interesting finding from work being done on hepatitis C infection and interferon alpha is a clinical trial that has found that by giving a polyunsaturated fatty acid supplement in the form of EPA (eicosapentaenoic acid) this can reduce the incidence of depression during interferon treatment. This may be relevant to CFS/ME because a small clinical trial has reported benefits from using EPA supplementation in CFS/ME.

    Prof Jonathan Edwards comments: “It is clear that there is overlap in some cases but also that there are different determinants of the two problems. In Hepatitis C, patients depression and fatigue were both problems but they occur at completely different times. Fatigue is almost immediate. Depression comes later.

    “Moreover, some patients have one without the other. And it is not just that depression takes a bit longer to kick in. Fatigue can continue for months or years after treatment in the absence of any depression. This presentation showed dissociation between depression and fatigue and clear evidence for the need to refine our approach to 'sickness behaviour'.”

    Sleep and CFS/ME
    Dr Sue Wilson (for Prof David Nutt), Imperial College London


    Prof David Nutt and his team are conducting a study looking at slow-wave sleep and daytime functioning in people with CFS/ME. This is a placebo controlled randomized cross-over clinical trial to assess the use of a drug called sodium oxybate, to increase the amount of slow wave sleep and to investigate whether this has an impact on next day function.

    “It’s very robustly shown that people with CFS/ME are sleepy in the day, and they have unrefreshing sleep,” explained Dr Wilson. “It’s possible that some of the fundamental mechanisms controlling sleep might be impaired. We also know that patients tell us that when they have better sleep, they feel better the next day. “So what if we give them something that will improve that slow-wave sleep? Would it make any difference the following day?”

    The team needs to recruit 12 patients, and use sodium oxybate [a proven treatment for excessive daytime sleepiness (EDS) and cataplexy associated with narcolepsy] to increase their slow wave sleep, which they measure using electrodes stuck to their heads over the course of eight nights in total. “It’s quite full-on for the patients to have this,” said Dr Wilson. “It’s tough for us as researchers, so it must be even tougher for them.”

    Several tests are conducted the following day, including multiple sleep latency test (a subjective test measuring how quickly you fall asleep in a quiet environment during the day), grip strength and cognitive tests.

    She ended by outlining the progress of the study so far, with four people having already taken part.

    Prof Jonathan Edwards comments: “I thought this was fascinating evidence for the need to look at very specific central nervous system pathways if we want to understand fatigue both on a broad basis and broken down into subgroups.”


    Mitochondrial function and cytokine production in skeletal muscle of patients with CFS/ME
    Prof Anne McArdle, University of Liverpool


    Prof McArdle began by saying that this project is almost completed in terms of sample gathering. “But what I can’t do today is show you any data because the project is blinded,” she continued. “We are finalising the collection of our blood samples in particular and we don’t want to compromise the analysis.

    “Hopefully what I can do instead is convince you that we are on the right track. I am going to show you some comparative data, particularly from our aging studies, to show you why we are taking this approach.”

    The study is exploring muscle abnormalities in CFS/ME through the use of new techniques which can more accurately assess the way in which the mitochondria – organelles responsible for energy production – are behaving in muscle in CFS/ME.

    This new research in Liverpool has made use of various experimental systems they have developed using both in vitro (studies on tissues removed from a living organism under artificial conditions in a laboratory) and in vivo (studies on tissues not removed from a living organism) experiments to look at the way in which mitochondrial function can be linked to cytokine changes.

    Prof Jonathan Edwards comments: “Prof McArdle gave us an account of how mitochondrial function, generation of reactive oxygen species and Adenosine triphosphate [how muscle cells biochemically store and use energy] handling in muscle are all tied in to signalling through cytokines like TNF. Muscle mitochondria are different from those in other cells in their position and density.

    “She described a range of experimental systems used in Liverpool both in vivo and in vitro to study the ways in which mitochondrial function might be linked in to cytokine changes. She indicated the importance of feedback loops that could potentially set up long-term abnormalities of regulation of muscle metabolism.”

    The epidemiology of CFS/ME in adolescence
    Dr Esther Crawley, University of Bristol


    Dr Crawley began by highlighting the clear need for investigating CFS/ME in children. “We are prevented from setting up adequate clinical services or conducting research because we don’t know the basics such as how common it is, what the natural history is, what the patterns of CFS/ME in children and adolescents are, and what causes it,” she said.

    This project’s objectives are to study prevalence and persistence of CFS/ME, its heterogeneity, and risk factors at different ages.

    Key findings so far include:

    · girls and boys are affected in equal numbers when younger, but by age 18 the incidence is twice as high in girls

    · each family adversity factor (eg. housing, education, financial pressure, relationships, substance abuse and crime) in pregnancy increases the risk of developing CFS/ME

    · Children report much higher levels of disabling fatigue at age 16 than their parents say they have

    · a relatively high proportion of children improve as compared to adults, although not all

    · symptom patterns differ with age, with less sleep disturbance and cognitive dysfunction in the younger groups

    · overlap with chronic widespread pain (the name given to fibromyalgia in children) seemed less than previously reported, with evidence for different determinants.

    This study will also look more at heterogeneity in more detail; and investigate risk factors using directed acyclic graphs, a method that allows researchers to examine causal relationships.
     
    Sasha, Bob, barbc56 and 5 others like this.
  3. Simon

    Simon

    Messages:
    1,914
    Likes:
    14,392
    Monmouth, UK
    PACE: A trial & tribulations
    Prof Peter White, Barts and the London School of Medicine and Dentistry


    Prof White gave us what he termed the ‘good news’ and the ‘bad news’ regarding to PACE trial. He started with an overview of the trial, which investigated using graded exercise therapy (GET), cognitive behaviour therapy (CBT), and adaptive pacing therapy (APT), all added to specialist medical care (SMC), and SMC alone, showing the results in terms of fatigue, cost effectiveness and serious adverse reactions.

    “Both CBT and GET were moderately effective, cost-effective, and safe if delivered individually by appropriately qualified therapists who are properly trained and supervised,” he said. APT was no more effective than SMC alone.

    Prof White continued by outlining the reactions to the PACE trial from some M.E. patient activists and organisations, which have to date included formal complaints (none upheld), petitions, and a total of 168 Freedom of Information (FOI) Act individual data requests (he had to count them all because he received an FOI Act request asking for the number.)

    “Criticism is fine, whereas vexatious complaints and harassment are not,” he said. “There are three reasons why this is important for the field.

    “Firstly, it’s not just the PACE trial that has had these problems – the scientists who wrote the first paper that failed to replicate XMRV findings encountered something similar. It happens whenever researchers find something that isn’t popular.

    “Secondly, it’s important because we are trying to encourage young scientists into the field, and we need to protect them and stop this happening to them.

    “Thirdly, it’s important because it damages science. We have some reasonable evidence that the campaign against the PACE trial affected our recruitment. We had to apply for an extension from the MRC in order to finish the trial.

    “The PACE trial has also played a small role in helping to amend the FOI Act for the better. From 1 October, current research will be exempt from the FOI Act so long as it can be shown that release of that data will be prejudicial to the conduct of the research.

    “I think it’s really important that we don’t just stay biological, or indeed behavioural, but integrate them, as you can see from this slide [CBT normalises cortisol response to wakening in CFS]: a so-called psychological treatment has changed the physiology for the better.

    “Perhaps most importantly, we need to stop being dualistic; believing that illnesses are either biological or psychological. They are both; a psychological event cannot happen without a biological event. In the future I hope that neurological and mental health conditions can be classified together as conditions of the nervous system.”
     
    Valentijn likes this.
  4. Quilp

    Quilp Senior Member

    Messages:
    211
    Likes:
    498

    Prof White gave us what he termed the ‘good news’ and the ‘bad news’ regarding to PACE trial. He started with an overview of the trial, which investigated using graded exercise therapy (GET), cognitive behaviour therapy (CBT), and adaptive pacing therapy (APT), all added to specialist medical care (SMC), and SMC alone, showing the results in terms of fatigue, cost effectiveness and serious adverse reactions.

    “Both CBT and GET were moderately effective, cost-effective, and safe if delivered individually by appropriately qualified therapists who are properly trained and supervised,” he said. APT was no more effective than SMC alone.

    Prof White continued by outlining the reactions to the PACE trial from some M.E. patient activists and organisations, which have to date included formal complaints (none upheld), petitions, and a total of 168 Freedom of Information (FOI) Act individual data requests (he had to count them all because he received an FOI Act request asking for the number.)

    “Criticism is fine, whereas vexatious complaints and harassment are not,” he said. “There are three reasons why this is important for the field.

    “Firstly, it’s not just the PACE trial that has had these problems – the scientists who wrote the first paper that failed to replicate XMRV findings encountered something similar. It happens whenever researchers find something that isn’t popular.

    “Secondly, it’s important because we are trying to encourage young scientists into the field, and we need to protect them and stop this happening to them.

    “Thirdly, it’s important because it damages science. We have some reasonable evidence that the campaign against the PACE trial affected our recruitment. We had to apply for an extension from the MRC in order to finish the trial.

    “The PACE trial has also played a small role in helping to amend the FOI Act for the better. From 1 October, current research will be exempt from the FOI Act so long as it can be shown that release of that data will be prejudicial to the conduct of the research.

    “I think it’s really important that we don’t just stay biological, or indeed behavioural, but integrate them, as you can see from this slide [CBT normalises cortisol response to wakening in CFS]: a so-called psychological treatment has changed the physiology for the better.

    “Perhaps most importantly, we need to stop being dualistic; believing that illnesses are either biological or psychological. They are both; a psychological event cannot happen without a biological event. In the future I hope that neurological and mental health conditions can be classified together as conditions of the nervous system.”[/quote]

    My bolding - what an absolute disgrace. I enjoy coming onto Phoenix Rising, but when I read posts like this I just want to log off and stay logged off. Others will speak more eloquently on the rest of his words. It wouldn't matter to me if he was a fringe member of a lunatic political party, but this man has power, influence, and very little to offer me as an M.E. patient.
    I just want to get better, we all do, but why should I engage, reason, compromise with someone like this, when I know he is so very very wrong.

    I need a break
     
    Min, rosie26 and Valentijn like this.
  5. Quilp

    Quilp Senior Member

    Messages:
    211
    Likes:
    498
    I'm not feeling too good right now, and yes this is yet another melancholy perambulation, that probably isn't even cathartic, even for me, but I cannot understand why this individual goes unchallenged, in the face of so much evidence.
    I am a nobody, a piece sh*t that Peter White wipes off his shoes after taking his dog for a walk, but I am a somebody who deserves to be listened to, we all do. But a hundred of me, is nothing to those that have the influence to challenge him.
    Am I mistaken, and that in back channels, diplomatic soundings shake the planet that this man calls home. Maybe, but I find it hard to believe that any such soundings are little more than mild bluster.
    Didn't voltaire, say that all it takes for bad things to happen, is for good people to let it happen ? And if he didn't say it I just did.
    How long does this have to carry on ? Will we ever be free from this ? The illness is the toughest fight of my life, and yet I feel like a man fighting two wars, two protagonists, and at times, it's harder to know, which fight is the harder.
    Sorry, but the bolding above is a dictators charter - and there is not a damn thing I can do about it.
    The toughest fight of my life just got tougher.
     
    Last edited: Oct 1, 2014
    meandthecat and catly like this.
  6. Simon

    Simon

    Messages:
    1,914
    Likes:
    14,392
    Monmouth, UK
    Acute infection & post-infective fatigue as a model for CFS
    Prof Andrew Lloyd, University of New South Wales


    An innovative study that tracked the development of CFS/ME after several different initial infecctions has revealed surprising findings about the role of the immune system and role of genetic variations in the susceptibility to post-infective fatigue.


    The sheep and cattle-farming outpost of Dubbo, four hundred miles inland from Sydney, Australia, was the surprising setting for a key CFS/ME study that put the development of the illness under the microscope. Prof Andrew Lloyd, an iinfectious diseases physician and immunology researcher from the University of New South Wales In Sydney, has documented the onset of CFS /ME in a tightly-defined subset of patients, and in the process has begun to unravel how CFS/ME develops after an infection.

    One of the main difficulties in CFS/ME research, Prof Lloyd argued, is ‘heterogeneity.’ All the evidence points to CFS/ME being a mixed bag of patients with potentially differeing disease processes giving rise to a reasonably similar set of symptoms.

    This diversity scrambles research findings, making it difficult to find a consistent set of abnormalities when comparing patients with CFS/ME and healthy individuals. In the 1990s, he tried to explore this problem by systematically analysing patient symptoms to identify subsets of the patient group with closely comparable illness characteristics.

    And indeed, he found two broad groups — but even there, the bigger group was a mixed bag. Lloyd concluded that the only way to make progress in the field was to zero in on a tightly-defined group of patients to see what went wrong as they fell ill. Cue the “Dubbo” studies of post-infective fatigue.

    Tracking patients

    The basic idea was simple: track patients from the start of an infection and then compare those that develop post-infective fatigue with those that have exactly the same infection at onset but recover promptly. The goal was to see what was different about those who became fatigued and those who did not.

    The team deliberately selected three very different infections which has something of a reputation as triggering prolonged illness:
    • Epstein-Barr Virus, EBV, a ‘great big DNA monster’ virus that causes the fever, sore throat and tender lymph nodes typical of glandular fever.
    • Ross River Virus, a tiny RNA virus spread by mosquito bites, which causes fever, rash and joint pain.
    • Coxiella burnettii, a bacterium that causes Q fever, usually picked up from sheep and cattle, which causes a nasty illness with high fever, and drenching sweats as well as inflammation of the liver.

    Prof Lloyd had two working hypotheses: the chronic fatigue would be either due to an infection that doesn’t go away, or to an immune system that remains stuck on after the infection is gone. He said that at the time he thought: “It’s going to be one or the other – or just possibly a combination. I'll sort it out quicktime, don't you worry!”, a comment that drew much laughter. He also suspected genes played a role.

    The key to the study was catching people early. They established good relationships with the local doctors so they were notified as soon as there was a new case of glandular Fever, Ross River virus infection, or Q fever. Self-report questionnaires and blood samples were collected regularly and those who remained unwell at 6 months were formally evaluated for CFS (Fukuda criteria) using medical and psychiatric exams as well as laboratory tests.

    Results

    All three infections led to a similar ‘natural history’, where the proportion of subjects with ongoing symptoms started high in the acute phase and gradually reduced over time, with fatigue being particularly persistent.

    upload_2014-10-1_18-23-15.png
    Regardless of the specific infection, around 10-15% formally met CFS criteria at 6 months, with approximately 6% still fatigued at twelve months and around 2% remaining fatigued for many years. Overall, this looked like a good model for studying CFS/ME.


    Severity of the acute infection is key

    Prof Lloyd and his team then started trying to identify factors that played a role in the development of long-term fatigue. It turned out that neither age, demographics, nor the presence of a psychiatric disorder prior to getting sick predicted fatigue. Nor, surprisingly, did the type of infection, with similar illness duration seen for all three.

    What did predict long-term fatigue (and CFS/ME status) was the severity of the initial illness. For example, the 10% or so, who were ill enough initially to be hospitalised had a 200-fold higher risk of CFS at six months. This graph shows the huge difference in recovery rates between the third of patients who were severlely affected in the acute illness (not just the hospitalised) and those who were least affected:

    upload_2014-10-1_18-25-53.png

    Cytokines can drive symptoms

    To begin tracking down the differences in what was happening in the bodies of those who developed CFS/ME, Prof Lloyd started thinking about the ‘acute sickness response’, just as Prof Dantzer had spoken about earlier in the day.

    What Prof Lloyd calls the ‘sickness response,’ and Prof Dantzer calls ‘sickness behaviour’ is the same – a biologically-driven process that is evolutionarily conserved across species because it gives survival value, helping the animal or human to focus on recovery from infection. Symptoms include fever, loss of appetite, muscle and joint pain, general malaise (feeling unwell), concentration problems and, of course, fatigue.

    Prof Lloyd began to wonder if sickness response had gone wrong could be a factor in post-infective fatigue, much as Prof Dantzer had wondered if it was a factor in cancer-related fatigue.

    Lloyd’s group wanted to revisit the early work on sickness response in animal studies “in the flesh – in humans”, using Dubbo patients. They examined the link between two key pro-inflammatory cytokines, IL-1 beta and IL-6, and symptoms during the early acute illness phase of Q fever patients. And they found the expected correlation between these cytokines and symptoms such as fatigue, muscle pain, poor concentration and malaise.


    Looking for chronic immune activation

    So then they tracked cytokine levels over time in the blood samples of their post-infective CFS/ME patients and matched individuals who recovered promptly from the same infection (without fatigue), in order to test the idea of chronic immune activation. They focused on the three key pro-inflammatory cytokines, IL-1b, IL-6 and TNF alpha.

    Unfortunately, this hypothesis didn’t pan out either: at three six and twelve months after the initial infection, levels of all three were no different between fatigued cases and recovered controls. ‘The chronic immune activation hypothesis was looking wobbly,’ said Prof Lloyd.

    Prof Lloyd pointed out that pro-inflammatory cytokine levels that his group had found in patients during the acute phase were present in nanograms per millilitre, which is the level at which they are biologically active.

    While some other studies have found elevated pro-inflammatory cytokine levels in CFS/ME patients (unlike his own study), those levels have been in picograms per millilitre, that is a thousand times lower, adding “it is not clear at all that that has biological meaning”.


    Looking for chronic infection

    To test the idea of chronic infection, they simply tracked evidence of persistence of the micro-organisms in the blood over time. They found that EBV, which causes glandular fever, did persist at measurable levels in the blood — but that’s normal for EBV, and crucially there was no difference between fatigued cases and recovered controls.

    For Ross River virus and Coxiella burnettii (Q fever), the pathogen was cleared rapidly, and again there was no difference between cases and controls. So that was it for the chronic infection hypothesis.


    Cytokine genes play a key role

    If it wasn’t chronic infection, and wasn’t persistently high cytokine levels, maybe there was something else that was driving the development of post-infective fatigue – and they focused in on the effect of inherited variations in genes which encode the immunological and neurological proteins likely to be involved in the sickness response.

    They suspected that some people might be genetically programmed to respond more to an infectious insult and so become more severely affected in the acute phase of infection and a greater likelihood of post-infective fatigue.

    Specifically, they looked at the genes for five cytokines: the three they’d studied before, plus interleukin (IL)-10 (which inhibits inflammation) and Interferon (IFN)-gamma (which promotes inflammation). There are high- and low-producing variants of each of these genes – could this be behind the different responses of patients?

    The results were striking. Patients with the high-producing version of IFN-gamma or the low-producing variant of IL-10 were much more likely to have severe symptoms. The effect was even more prominent in those with the combination of these ‘risky’ genes, showing that:

    • those with one copy of the high-producing IFN-gamma gene were more likely to develop severe symptoms than those with only the low-producing IFN-gamma gene, with an odds ratio of 2.6 (where an odds ratio of 1 means no difference between two groups)
    • those who had both copies as the high-producing version were even more likely to have severe symptoms: the odds ratio was 2.9
    • those with a double whammy of both high-producing IFN-gamma genes and low-producing IL-10 genes had an odds ratio of 6.8, which is a really big effect.
    The team also showed that those with the ‘high-producing’ gene version really did produce more cytokine during the acute phase of the illness. Overall, the type of IFN-gamma and IL-10 genes significantly affected illness severity, cytokine protein levels, and the duration of illness —independent of age, gender and even the specific infection type.

    “How long you are going to be remain unwell after these acute infections is at least partly determined by your genetic makeup,” Prof Lloyd said, “in particular those two genes.”

    However, these genes only explained some of the difference in illness severity between patients, so while they were part of the story, there must be other factors at play too. The team also looked at neuro-behavioural genes (for example, those that affect levels of neurotransmitters) and reported promising results on one, snappily called P2X7.

    P2X7 is a neuro-immune gene that has been linked with psychiatric and neurological disorders. It’s also very important immunologically, affecting, for example, recovery prospects from tuberculosis. And Lloyd’s groups has now found that it may play a role in fatigue.

    A cell-surface receptor that appears on both white blood cells and on microglia, the brain’s immune cells, P2X7 helps regulate inflammation, playing a specific role in the release of pro-inflammatory cytokines, including our old friend IL-1 along with IL-18, which stimulates release of IFN-gamma from T-cells. When it’s activated, P2X7 acts as a pore, allowing transport of the energy molecule, ATP, across the cell membrane.


    In short

    Prof Lloyd summed up by returning to his original hypotheses that post-infective fatigue was driven by chronic infection or chronic immune activation. This didn’t pan out: there was no difference between fatigued cases and recovered controls in either pathogen levels or cytokine levels.

    The new hypothesis is that “stuff happens” in the acute infection, he said to laughter, though exactly how it happens isn’t clear. Severity of the acute infection predicts post-infective fatigue and our genetic make-up plays a role in both. He said if he had to choose a site where those genes play out, it might be in the body in the acute phase, but in the prolonged phase it’s going to be in the brain. Prof Lloyd added “we need to get over blood” – the answer probably lies “upstairs”.


    Future plans

    There is a new post-infective fatigue study under way (more conveniently located in Sydney) that will be looking at autonomic factors and circadian rhythms. And, said Prof Lloyd, they wanted “to really get to the money” - by imaging activated microglia in the brain. (In answer to a later question from Prof Ian Lipkin, Prof Lloyd pointed to evidence in mice that an initial acute inflammation in the body can lead to long-term activation of microglia in the brain. Perhaps something similar is happening in CFS/ME cases that develop after infection.)

    He also stressed the importance of using challenge testing. “If we are to continue to look at the blood, we need to use studies in which we carefully make the fatigue worse – transiently, to look at post-exertional exacerbation”, which he described as being “tough for the patients but good for the scientists!”

    They are using a cycling exercise as a physical challenge and, intriguingly, they are also using a driving simulation as a cognitive challenge. Both trigger an exacerbation which comes on over hours and lasts a day or two and then resolves – this offers real opportunities to look for biologlocal factors which correlate with the changes in fatigue.

    It looks like Prof Lloyd’s group is well set up to reveal yet more about how CFS/ME develops after an infection.
     
    meandthecat, Sasha, RustyJ and 7 others like this.
  7. Simon

    Simon

    Messages:
    1,914
    Likes:
    14,392
    Monmouth, UK
    Plenary session four: Pain, paediatric CFS and epidemiology

    Understanding pain mechanism in children and adolescents

    Prof Maria Fitzgerald, University College London

    The epidemiology of adolescent CFS and chronic widespread pain

    Prof Jon Tobias, University of Bristol


    Recovery and persistence from CFS/ME in adolescents

    Dr Roberto Nuevo, University of Bristol


    Understanding pain mechanism in children and adolescents
    Prof Maria Fitzgerald, University College London

    “I think it’s very striking there are few studies of pain in CFS/ME patients,” began Prof Fitzgerald. “The field of chronic pain is huge and well-funded, with many people working in it – cancer pain, chronic back pain – but apparently nothing in this area.”

    She outlined the concept of central sensitisation, the idea that the central nervous system amplifies the input that comes directly from the peripheral nerves in muscles and joints.

    She refuted what she called the Cartesian idea that pain is caused solely by stimulating nociceptors (nerve endings) communicating with the brain, that more stimulation equals greater pain, and that if the pain continues, there must be a biopsychosocial reason. “This is simply not the case,” she said.

    “Instead, there is very good evidence for circuits at low levels of the central nervous system, particularly in the dorsal horn of the spinal cord, that are able to modify this input as it comes in, before it even gets to the brain.

    “Everybody has in them the mechanism needed to amplify pain. Most of the time, we don’t – but it can happen to everyone.”

    Prof Fitzgerald then described how, in chronic pain patients, the state of central sensitisation becomes fixed. This may be because there is a continued source of pain – eg. in chronic back pain – but it may also continue even with no injury present.

    There is still debate that this is the mechanism underlying the chronic widespread pain of CFS/ME. It’s possible that descending controls from the brain may set up central sensitisation, says Prof Fitzgerald, but we simply do not know if that is true.

    There is very strong evidence that the brain can influence pain processing at spinal cord level.



    Expectations of pain

    Prof Fitzgerald outlined a study which tested healthy subjects’ expectations of pain. It found that, compared to controls, the same stimulus produced less activity at spinal cord level in those who believed they were using a pain-reducing cream (which was in fact a placebo).

    “If this can happen in healthy people, why could it not be manipulated in people who are ill for whatever reason?” asked Prof Fitzgerald.

    Another very well-established way that central sensitisation might be maintained is by neuroimmune activation, with microglia releasing cytokines.

    However, Prof Fitzgerald stressed that, in the pain field, nobody is looking at cytokine levels in the blood.

    “Instead, we are interested in what’s happening to the nociceptive pain circuits in the central nervous system. They don’t really expect a chronic pain patient to have masses of circulating cytokines – what they know to be true is that, with stimulation, these microglia release tiny amounts of cytokines in the area of the circuit, which excites them and, in other words, they hurt.”

    But why is it that some people have terrible pain, even when there is apparently no original injury it can be traced back to? Prof Fitzgerald outlined very new research that points to us all being in a state of latent central sensitisation, which healthy individuals are able to suppress all the time.

    One explanation might that infants suppress neuropathic pain following nerve injury by ‘blocking’ anti-inflammatory activity, so a constant state of central sensitisation may be due to a very early life event that we may not even remember. “This may account for why neuropathic pain is rare in young children and also why it can emerge, for no observable reason, in adolescent patients,” says Prof Fitzgerald.



    Latent sensitisation

    Finally, explaining that this is an idea based on experimental evidence, she referenced a recent paper (Corder et al, Science, 2013) which suggests that every time adults are injured, a natural endogenous analgesia kicks in to suppress the pain – but that the pain continues for a considerable time after, even though we can’t feel it.

    “This makes us think a bit differently about pain,” says Prof Fitzgerald. “A lot of it is happening a long time after an injury, but if we are healthy and well we are actively suppressing it.

    “How is going to help people with CFS/ME? This way of thinking about pain, in terms of its time course, location, spatial distribution, intensity and so on, has been driven by basic research, not clinical observations. It informs and stimulates better treatments.

    “How do I know that? For the first time, just published – this morning, in fact – there has been a randomised, controlled, double blind, stratified trial of carbamazepine in neuropathic pain, based on precise sensory profiling (Demant et al, Pain, 2014). They found that one group responded amazingly well, and the other two groups did not.

    “If you understand the basis of pain, it improves treatment.”


    Dr Esther Crawley comments: “Pain is a strong predictor of poor outcomes in our CFS/ME patients, and I think the idea of improving stratification with pain is really important.”

    Prof Jonathan Edwards comments: “What I thought was brought out particularly clearly by Prof Fitzgerald and Prof Pariante ,in different ways, was the fact that discrepancies in a broad brush view are emerging that might lead us to a specific answer for CFS/ME.”


    The epidemiology of adolescent CFS and chronic widespread pain
    Prof Jon Tobias, University of Bristol


    Data from the UK CFS/ME National Outcomes Database found that 28% of adults with CFS/ME also have fibromyalgia.

    Prof Tobias was presenting on behalf of his colleague, Kevin Deere, who has looked at the relationship between this and CFS/ME in 17 year olds, which no previous studies have done from an epidemiological perspective.

    The research aims were to see if CFS/ME and chronic widespread pain (CWP, which is related to fibromyalgia and more easy to evaluate based on questionnaires) tended to co-exist in adolescence, and to see if these conditions share common risk factors. The analyses were performed in a large population based cohort of adolescents (using the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort) in whom they assessed the presence of both CFS/ME and CWP by questionnaire (CWP was derived from questions asking about pain duration and location

    “We went on to use logistic regression to determine if CFS/ME was a determinant for chronic widespread pain, and vice versa,” explained Prof Tobias. “We also looked at other risk factors including gender, maternal education, obesity, depression and anxiety.

    “We found that CWP was associated with an increased risk of CFS/ME at a ratio of 3.5% in our initial analysis, but this was attenuated quite markedly when we adjusted for our other risk factors.”

    “Similarly, we found that CFS/ME predicted CWP, again at 3.5%, again largely attenuated by these other confounders.”

    In addition:
    • there was only weak evidence for an increased risk of CWP in CFS
    • being female was associated with an increased risk of CWP but not CFS
    • depression was associated with an increased risk of CFS but not CWP
    • anxiety was associated with an increased risk of both conditions.

    Prof Tobias explained the limitations of the study, in that the CWP phenotype is only a proxy measure for fibromyalgia, which is a clinical definition; and also that using even a large population for such a study may not be sufficient, with alternatives including case controlled studies.

    “The overlap we found does seem to be somewhat less than in adults. What was also interesting is that the associations between depression and gender were distinct, suggesting different aetio-pathological mechanisms.”


    Recovery and persistence from CFS/ME in adolescents
    Dr Roberto Nuevo, University of Bristol

    There is little evidence about persistence or recovery of CFS/ME in adolescents, says Dr Nuevo, whose study aimed to describe the epidemiology and natural course of CFS/ME in patients between the ages 13 and 18.

    This study also used the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort, and investigated the presence of CFS/ME at three time points using parental reports (13 years), parental and child report (16 years) and child reports (18 years).

    Dr Nuevo described the prevalence of CFS/ME at ages 13, 15 and 18 years, the natural history and the chance of recovery. As these are unpublished results, more information cannot be shared in this report.


    More to follow including patient session...
     
  8. Simon

    Simon

    Messages:
    1,914
    Likes:
    14,392
    Monmouth, UK
    Associate Member/patient and researcher session

    • Working together for more and better research that benefits people with CFS/ME, a workshop facilitated by Sally Crowe
    • Panel discussion for researchers and Associate Members, chaired by Prof Stephen Holgate, CMRC Chair
    Unfortunately the Workshop overview has a lot of tables that won't reproduce on the forum, so I suggest you download the pdf

    Panel discussion for researchers and Associate Members
    Prof Stephen Holgate, CMRC Chair

    The following researchers gave a short overview of their work, picking out their key findings and explaining why they were important:

    • Prof Robert Dantzer (see p X)

    • Prof Andrew Lloyd (see p X)

    • Prof Ian Lipkin (see p X)

    • Dr Stuart Watson (see p X)

    • Prof Wan-Fai Ng (see p X)

    • Prof Carmine Pariante (see p X)

    • Dr Sue Wilson (see p X)

    • Prof Anne McArdle (see p X)

    • Dr Esther Crawley (see p X)



    The panel then took questions from the audience.

    The first question was to Prof Pariante regarding fatigue in his cohort of Hepatitis C patients. Able to observe onset and duration of fatigue once Interferon-alpha treatment starts, he then monitors recovery once treatment stops.

    “Data is still being collected,” he said, “but there does not seem to be a direct relationship between the improvement and viral infection.” Some people remained profoundly fatigued despite completely clearing the virus and their general health improving, he said. For others, the opposite was true: their fatigue abated once treatment stopped, even though the infection was still present.

    Prof Pariante concluded, “So unfortunately it [fatigue] is not directly related to the virus. I think it’s more about how the body responds to this massive, massive inflammation and obviously some people will be more sensitive to that.”
    ---

    Next, a patient explained that he had had severe fatigue and brain fog when he first got M.E. “I went from being a programmer and holding everything in my head to not knowing what day of the week it was,” he recalled. “I could barely walk anymore.” He felt that unless someone had these symptoms they didn’t have M.E. and continued, “I feel very strongly that we have to tighten up the criteria on what M.E. is and what it isn’t.”

    The bigger picture
    “I think you make some excellent points but I would caution you against trying to make the overall umbrella too small,” replied Prof Lipkin, stressing the importance of looking at the bigger picture. “It’s very difficult to get funded to do research in this arena. I think if you talk to my colleagues they will tell you this is a huge challenge, and has been now for decades.”

    However, there are organisations that are very successful at pulling in big money. “If you use cancer as an analogy, the American Cancer Society is very useful for all the people who have different types of cancer to come together under one banner and get the resources to support a whole range of cancers.”

    There was a problem with that, said the patient. If you applied therapy to a mixed bag of people you got skewed results.

    “Absolutely, I agree with you completely,” replied Prof Lipkin. “At the level of investigating pathogenesis, which is how you get ill in the first place, or [if you’re looking at] ways in which people respond to different kinds of therapy, there, it’s very important to parse narrowly.”

    Using a whole range of symptoms and biomarkers is useful in describing specific groups of people, he said. “From the vantage point of science and doing research, you should find ways in which you can be more discrete in terms of thinking about mechanism and disease.”

    Picking up this theme, Prof Dantzer drew on his experience in cancer research and agreed it was really important to cast the net wide at first. “The symptom such as fatigue never happens by itself, it happens in a cluster of other symptoms and we see that very well in cancer patients.”

    There will be common mechanisms, he said, such as inflammation or mitochondrial dysfunction but they may present similarly or differently in a given selection of patients. He suggested the need to study all symptoms, only pulling out the differences at a later stage.


    Perceptions of the condition

    “Does the panel think that a different perception of ME and CFS would actually help improve the availability of funding?’ asked a UK film producer working on a film about CFS/ME, Canary in a Coal Mine.


    “From the children’s perspective,” said Dr Crawley, “they would say they really need a different public perception to enable them to go back to school, to enable them to talk to their friends, even just to enable them to talk to their siblings. This is a very stigmatising illness, particularly for children and we should take every opportunity to talk about how devastating the illness is.”


    Dr Crawley felt taking a drip, drip, drip approach was necessary to change the public perception of CFS/ME, and that events such as this patient-researcher session and working together were really important to achieve this.


    Referring to his work on the 2011 film Contagion, which generated worldwide exposure for issues related to his own field of emerging infectious diseases, Prof

    Lipkin suggested that a well -known narrator for the producer’s documentary was critical. “You need to get somebody who is visible and well known who can promote something you are trying to do, otherwise it just gets lost.”


    Selecting patients for research

    A patient commented to the panel that if the principle selection of patient cohorts is flawed then so are the results. He suggested using the Canadian Consensus Criteria to avoid this problem.

    “Your point is that if the wrong people go into the research, then the research becomes pointless,” reflected Dr Watson. “I think you’re both right and wrong all at the same time.”

    He explained that in a recent study at Newcastle, they had selected candidates very carefully, excluding anybody who had a current or previous episode of a psychiatric disorder like depression or anxiety. Consequently they had found different results from previous studies regarding childhood adversity.

    Agreeing with the rest of the panel, Dr Watson emphasised that looking at a broad range of symptoms was important.

    “We wanted to characterise patients very well,” he said, “and so we recorded lots of different things and one of the things that we recorded was pain in the jaw.” It threw up some interesting results.

    “We found that those with chronic fatigue and jaw pain were different to people who had chronic fatigue and didn’t have jaw pain.” Primarily, they found a difference in cognitive performance and brain fog.

    Though these might be chance findings, Dr Watson said that stratifying within this umbrella allowed them to draw out differences that were potentially markers of separate biological processes. He concluded, “Inclusivity but stratification is the message that is coming through across the panel, I think.


    Purpose of criteria

    Prof Lloyd, involved in both the Australian criteria and reviewing the Center for Disease Control and Prevention case definition, said there were now a total of 11 different criteria sets for CFS/ME.

    “One thing I would advise is to be very clear about the purpose of the criteria,” he added. “From the point of view of making a diagnosis, the criteria broadly matter but actually what really matters is the care that leads from the diagnosis.”

    This was a completely different issue for criteria for entry into a clinical trial or a research study, he said, where it was important to understand the similarities and differences within the disorder.

    “I have the strong sense that we could generate another thirty criteria and it won’t advance the cause. My sense is we need to get on and do good quality research, characterising our patients by a broad range of characteristics, using various criteria to understand their similarities and differences and then to understand what the biology of the disorder is.”

    Prof Holgate summed up this part of the discussion, saying, “The whole idea of stratifying this condition is obviously a major topic, and something we’ll be talking about as we move this whole field forward.”

    Referring to his own speciality of bronchial asthma, Prof Holgate explained how classification was by severity because it linked to therapeutic options. But as it was now known that there are at least six different variants of asthma, he feels that, in fact, this hides ignorance about the illness.


    What we call CFS/ME

    A patient wondered about the meaning of chronic pain syndrome, asking Dr Crawley,

    “Isn’t it just another term to confuse things?”

    “What you call fibromyalgia in adults presents slightly differently in children, so we tend to call it chronic pain syndrome,” said Dr Crawley. “I completely agree it’s likely to be a fibromyalgia type problem,” she added, but that ultimately she didn’t choose what to call it.

    Prof Holgate acknowledged that there is anger around certain terms, and drew attention to the Multiple Sclerosis Society, which has been very successful in raising funds and its profile.

    “They’ve got one word, but there is likely to be 30 diseases under that one heading with different pathways and different factors,” he explained. “I think that is part of the problem. We have this acronym, called chronic fatigue syndrome or ME, or fibromyalgia if you want to blur the edges. It really adds to the confusion and it gives a false security that we understand what we’re talking about.”

    Once the biological pathways become clear, he said, there will be a way of renaming this disease, or range of diseases, based on the driving mechanisms. “And the sooner we get to the mechanistic pathways the better,” he concluded. Finally, he asked Prof Lloyd if they have the same problem with naming it in Australia.

    “I think we’re a bit more laid back, to be honest,” replied Prof Lloyd languidly, and the audience burst into laughter.


    Integration of services

    A carer asked if adult CFS/ME services were going to be integrated in the same way as children’s services. Her son had fallen ill at 15 and had lots of people investigating in a joined-up way, she said. But as soon as he turned 16, he was considered an adult and was looked after by a variety of departments who failed to communicate with one another.

    “I think that is really, really important, that sense of bringing people together with different skills” said Dr Watson, explaining that they are attempting this at Newcastle by, for example, drawing together immunology and autonomic research, and attempting to coordinate at a clinical level and a research level.

    “I think in a way this meeting is about that,” said Prof Holgate, “about joining things up, not splitting them apart.” Referring to the fragmentation in services, he said the same problem had existed in adult cystic fibrosis and that, “in the end, they had to redesign adult services.”


    Translational research
    A complementary practitioner said he would like more diagnostic tests available, including one for measuring cortisol.

    “I think the important point you are trying to make is that there is scientific underpinning of the mechanisms that are involved in this disease,” reflected Prof Holgate. “And these need to be linked to some of the therapeutic outcomes that you actually deliver within your different clinical domains.”

    Prof Lloyd felt that new approaches should be underpinned by research evidence. “We don’t yet have that,” he said, “science has to drive the outcomes.” But typically with science, moving from discovery into impact is a slow process.

    “We need to make sure that the outcomes that are emerging out of the research are captured by the people who then develop that next phase,” said Prof Holgate. “We need to pick them up and run with them.”


    Co-morbidities

    An audience member said that gut problems such as IBS were common in people with ME and asked if that linked to recovery.

    “Co-morbidities are obviously massive subject,” confirmed Prof Holgate, citing fibromyalgia, allergies and joint pain as just some of the illnesses and symptoms that were linked to ME/CFS.

    Dr Crawley agreed co-morbidities should be investigated further. “This goes back to what all of us have been saying, which is that you need really well classified patients. We need to follow them and describe them and their co-morbid disorders. We just finished a study looking at eating disorders and symptoms, which are a really big problem in children. I completely agree we need to look at it in more detail.”


    Prof Holgate concludes
    The session ended with Prof Holgate thanking all those who had attended. He kept the door wide open for further collaboration with patients.

    “What would be interesting is if you wanted to send in any questions that you have to us, we can reflect on those,” he said. “So if you have issues you want to raise, put them in an email, put them on paper and let us know. We’ll discuss them and think about them.”

    Further patient-researcher sessions could also be arranged, if people had liked the way it had been done. The audience applauded enthusiastically.

    “Don’t forget, for the Collaborative,” said Professor Holgate, “this isn’t the end of the meeting: this is the beginning of the journey.”
     
    Sasha, Bob, Valentijn and 3 others like this.
  9. Ruthie24

    Ruthie24 Senior Member

    Messages:
    197
    Likes:
    392
    New Mexico, USA
    Thanks Simon for your excellent reporting. Well done!
     
    Sasha, rosie26, Kati and 5 others like this.
  10. Simon

    Simon

    Messages:
    1,914
    Likes:
    14,392
    Monmouth, UK
    Thanks - I only wrote the Andrew Lloyd piece on this page.
    Full credits:
     
  11. aimossy

    aimossy Senior Member

    Messages:
    1,089
    Likes:
    3,760
    Andrew Lloyd:balloons:
    Brilliant work I thought!
    Thank you @Simon !
     
    Sasha, rosie26 and Simon like this.
  12. Min

    Min Guest

    Messages:
    1,386
    Likes:
    1,927
    UK
    Thank you Simon

    One wonders why Peter White was permitted to spout his vile propaganda in the middle of what sounds an excellent conference.

    Shame on Action for ME, the ME Association and Action for Young ME for collaborating with him and Crawley.
     
    Wildcat likes this.
  13. Dolphin

    Dolphin Senior Member

    Messages:
    10,635
    Likes:
    28,033
    Thanks to whoever did the write up Simon. These sorts of figures show the large percentage that recover in the period 6 months to 2 years.

    I think it would be interesting if they looked again at the data for those who had a long-term illness and see what their immune system looked like: their study has included a lot of people on their way to recovery.
     
    Last edited: Oct 4, 2014
  14. Dolphin

    Dolphin Senior Member

    Messages:
    10,635
    Likes:
    28,033
    Interesting.
     
    lycaena, Bob and Kati like this.
  15. Dolphin

    Dolphin Senior Member

    Messages:
    10,635
    Likes:
    28,033
    I wonder whether the underlined bit is an error, as I don't think Prof. Pariante is studdying Sjogren's syndrome patients.
     
  16. Dolphin

    Dolphin Senior Member

    Messages:
    10,635
    Likes:
    28,033
    I wonder about this. Generally ME/CFS is diagnosed less often in lower socio-economic groups, although that may be an artifact of who gets diagnosed.

    I think Esther Crawley generally uses the broad NICE criteria, so the study may include people with other types of fatigue e.g. from lack of sleep, poor health/nutrition, stressful environment, affective disorders, etc.
     
    Valentijn likes this.
  17. Dolphin

    Dolphin Senior Member

    Messages:
    10,635
    Likes:
    28,033
    One person said that PDW gave an example. I'm still interested in knowing more. My guess is that it could be an atypical example of somebody who did well, but I could be wrong.
     
    Esther12, Valentijn and Kati like this.
  18. Dolphin

    Dolphin Senior Member

    Messages:
    10,635
    Likes:
    28,033
    I have a soft spot for believing biochemical factors, rather than central sensitisation, explain a lot of the pain. Levels of oxidative stress have been associated with symptoms. Also, the Newton team found patients were exposed to 50 times the level of acid after exercising.

    Anecdotally, before the illness, I think I had a reasonably high pain threshold e.g. I loved playing contact sports like rugby. I'm not convinced in my case anyway inherited factors or early childhood factors are that important for the pain I can suffer.
     
    Valentijn, Bob and Kati like this.
  19. Dolphin

    Dolphin Senior Member

    Messages:
    10,635
    Likes:
    28,033
    I don't understand the 3.5% figure - I wonder is it simply 3.5?

    I tend to not have much confidence with these studies looking at factors pre-CFS because it can often take a long time to get diagnosed so the person may actually have had CFS in the period, which might be misinterpreted as depression or anxiety. Also, being undiagnosed with CFS certainly would increase the chances of being anxious or depressed.
     
    Esther12, Valentijn and Kati like this.
  20. jimells

    jimells Senior Member

    Messages:
    1,997
    Likes:
    6,095
    northern Maine
    I dunno. I kinda feel sorry for him. Imagine speaking at an international conference attended by well respected researchers and clinicians. Now imagine that your talk is greeted by a giant yawn.

    Mr White, would you like a piece of humble pie to go with your whine about being vexated? ("vexatious complaints")

    I think allowing him to speak at the conference was a brilliant move. The chilly reception must've made a big impression on the Wessely School of Denial. I expect eventually they will slink back into their ivory tower, never to be heard from again.
     
    Cheshire, Kati and Valentijn like this.

See more popular forum discussions.

Share This Page