CFS symptom profiles in UK & Netherlands

Posted on 01/05/2016 by wames

Research highlights:

• We explore chronic fatigue syndrome (CFS) phenotypes in two large clinical cohorts.
• Adults with CFS may have one of 6 symptom-based phenotypes.
• Phenotypes were associated with sex, duration of illness, and comorbidity.
• Polysymptomatic patients had more severe illness and more comorbidities.
• Phenotypes in UK patients were replicated in Dutch patients.

Abstract

Objective: Studies have provided evidence of heterogeneity within chronic fatigue syndrome (CFS), but few have used data from large cohorts of CFS patients or replication samples.

Methods: 29 UK secondary-care CFS services recorded the presence/absence of 12 CFS-related symptoms; 8 of these symptoms were recorded by a Dutch tertiary service. Latent Class Analysis (LCA) was used to assign symptom profiles (phenotypes). Regression models were fitted with phenotype as outcome (in relation to age, sex, BMI, duration of illness) and exposure (in relation to comorbidities and patient-reported measures).

Results: Data were available for 7,041 UK and 1,392 Dutch patients.

Almost all patients in both cohorts presented with post-exertional malaise, cognitive dysfunction and disturbed/unrefreshing sleep, and these 3 symptoms were excluded from LCA. In UK patients, six phenotypes emerged: ‘full’ polysymptomatic (median 8, IQR 7-9  symptoms) 32.8%; ‘pain-only’ (muscle/joint) 20.3%; ‘sore throat/painful lymph node’ 4.5%; ‘oligosymptomatic’ (median 1, IQR 0-2 symptoms) 4.7%.

Two ‘partial’ polysymptomatic phenotypes were similar to the ‘full’ phenotype, bar absence of dizziness/nausea/palpitations (21.4%) or sore throat/painful lymph nodes (16.3%). Women and patients with longer duration of illness were more likely to be polysymptomatic. Polysymptomatic patients had more severe illness and more comorbidities. LCA restricted to 5 symptoms recorded in both cohorts indicated 3 classes (polysymptomatic, oligosymptomatic, pain-only), which were replicated in Dutch data.

Conclusions: Adults with CFS may have one of 6 symptom-based phenotypes associated with sex, duration and severity of illness, and comorbidity. Future research needs to determine whether phenotypes predict treatment outcomes, and require different treatments.

Chronic fatigue syndrome (CFS) symptom-based phenotypes in two clinical cohorts of adult patients in the UK and The Netherlands, by Simon M. Collin, Stephanie Nikolaus, Jon Heron, Hans Knoop, Peter D. White, Esther Crawley in Journal of Psychosomatic Research, February 2016 Vol 81, Pages 14–23

 

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CFS/ME pathophysiology, diagnosis & treatment overview

Posted on 01/04/2016 by wames

Review abstract:

The underlying pathophysiology in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is unclear, and there is disagreement in the field over diagnostic criteria and treatments. Here, we review the literature and comment on the debate around this condition.

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a common – and serious – condition characterised by pervasive fatigue (particularly after minimal exertion) and chronic pain as well as impairments in concentration and memory (1).

Pathophysiology

Heredity can predispose to chronic fatigue syndrome/myalgic encephalomyelitis (2), as can certain personality traits such as high levels of perfectionism (3). Long-lasting infections, such as mononucleosis, are established triggers (4), but critical life events can also play a part (5).

Maintaining factors include altered cognitive function, especially executive dysfunction (6), increased sympathetic and decreased parasympathetic nerve activity, which affects cardiovascular regulation (7, 8), and reduced responsivity of the hypothalamic-pituitary-adrenal axis (HPA axis) (9).

A number of studies have also reported immunological changes characterised by mild systemic inflammation (increase in proinflammatory cytokines) and impaired NK cell function (10), but here there are contradictory findings. One problem is publication bias, whereby sporadic positive findings are reported because they are original and exciting, but in time turn out to be false positives.

This problem was illustrated in a recently published review article (11). The authors examined 38 articles featuring a total of 77 immunological markers, many of which were reported as positive in single studies. The only replicated positive marker was TGF-β, the others were negative in the vast majority of studies. Whether TGF-β is a biomarker for chronic fatigue syndrome/myalgic encephalomyelitis remains to be shown. Several of the studies upon which the review was based used biological material that was collected in a suboptimal manner, and techniques that are now out of date.

We assayed 27 cytokines (excluding TGF-β) in the plasma of a group of patients to test the hypothesis that the patients had mild systemic inflammation (12). There were no differences from a comparable control group, either in the main analysis or in subgroup analyses. Our negative findings were published in a high impact journal, thereby helping to counter publication bias.

Integrated models have been developed in which empirical findings from research on chronic fatigue syndrome/myalgic encephalomyelitis are not viewed as contradictory, but rather as distinct facets of a complex phenomenon (13 – 15). A good place to start may be the patients’ overwhelming fatigue.

Neurobiological studies indicate that fatigue may have commonalities with pain, both in terms of neurological substrate (partially overlapping neural networks) and evolutionary function. Where pain perception is an «alarm» about tissue damage, fatigue may be an «alarm» about excessive energy expenditure (16, 17). Activating the «fatigue alarm» ensures that the individual rests, but at the same time – in common with pain – activates a stress response characterised by cognitive, neuroendocrine and immune changes. Evolution dictates that both «alarms» must be plastic – they must be modified by learning to ensure that maladaptive behaviours are not repeated. The «alarms» must also have high sensitivity – they must be activated by all potentially threatening situations. However, the price of this evolutionary adaptation will be a high risk of «false alarms».

It is plausible that chronic infection may trigger a «false fatigue alarm». Initially, the immune response will be directly responsible for the fatigue because proinflammatory cytokines (such as interleukin-1β) affect the brain (18). But the longer the immune response lasts, the greater the risk of an association with neutral stimuli through classical conditioning (19). The «fatigue alarm» and accompanying stress response may then continue even if the infection spontaneously resolves and the immune response is normalised (20).

A sustained stress response may in turn account for many of the maintaining factors in chronic fatigue syndrome/myalgic encephalomyelitis (13). Stress responses affect cognitive functions (21), are marked by increased sympathetic and decreased parasympathetic nerve activity (22) and can reduce HPA axis responsivity over time (23), analogous to what is seen in chronic fatigue syndrome/myalgic encephalomyelitis. This will in turn have immunological consequences: Increased catecholamine levels, reduced parasympathetic nerve activity and reduced HPA responsivity promote the inflammatory response (24 – 26).

Empirical findings in chronic fatigue syndrome/myalgic encephalomyelitis may thus be related as shown in Figure 1. This model is in keeping with established knowledge on treatments: Cognitive behavioural therapy can be thought of as a method for «unlearning» a «false fatigue alarm». The sympathetic inhibitor clonidine normalises parts of the stress response in chronic fatigue syndrome/myalgic encephalomyelitis, but does not improve symptoms or functioning – a likely explanation is that clonidine does not affect the «fatigue alarm» itself (27).

While we believe this to be the most plausible model of the condition’s pathophysiology, further research is needed to confirm or disprove it. One strategy might be functional imaging of the central nervous system: preliminary results from our research group suggest functional changes in the brain regions that control the stress response.

Diagnostics

There are no biomarkers for chronic fatigue syndrome/myalgic encephalomyelitis; the diagnosis must therefore be based on the patient’s description of their symptoms. The most widely used set of criteria (from 1994) requires prolonged (6 months), unexplained and incapacitating fatigue, while at least four of eight accompanying criteria must also be fulfilled (28). This definition was based on a pragmatic consensus and has subsequently been criticised. The requirement for four of eight accompanying criteria, for example, has no rational basis and is not supported by empirical validation studies (29, 30).

Subsequent developments have tended towards definitions that are, in some cases, less detailed; in others, more so. For example, the British NICE criteria (31) require chronic fatigue and one additional symptom, whereas the Canadian criteria (32) and the closely related «international consensus criteria» (33) have extensive symptom requirements. All in all, 20 different definitions have been proposed, but none has been thoroughly validated (34).

Based on existing evidence, we recommend a broad diagnostic definition, both scientifically and clinically. The reasons are several:

  • A broad definition allows subgroup analyses based on a more detailed set of criteria, which helps with validation. Using such an approach, we have shown that the Canadian criteria seem to lack discriminant and predictive validity (35)
  • The detailed definitions presuppose a clear association between symptoms and underlying pathophysiology. Empirical data indicate, however, that this assumption is incorrect: In adolescents with chronic fatigue syndrome/myalgic encephalomyelitis, for example, there was no association between symptoms that might suggest an inflammatory process (such as feverishness, tender lymph nodes) and plasma markers of inflammation (12)
  • Persons with chronic fatigue require medical assistance – a broad definition would ensure that patients in need of help do not slip through the net

Treatment

A systematic review from 2006 concluded that cognitive behavioural therapy is the treatment with the most evidence to support it (36). This conclusion has subsequently been strengthened through several large-scale studies of adults and adolescents (37 – 40), and the evidence base now includes several thousand patients. The effect size is, however, modest, and there is limited evidence of efficacy in the sickest patients.

Cognitive behavioural therapy can be given both individually and in groups (37). In adolescents, internet-based consultations may be effective (39). Individually adjusted increases in activity are an integral part of cognitive behavioural therapy but may also have a beneficial effect alone (38, 40, 41). There is no sign of any increase in serious adverse events following these types of treatments (38, 41, 42).

With the possible exception of the immunomodulatory drug rintatolimod, a recent systematic review failed to show efficacy of any pharmaceutical therapies for chronic fatigue syndrome/myalgic encephalomyelitis, be it immunoglobulins, hydrocortisone, selective serotonin reuptake inhibitors or antiviral agents (38). In Norway, treatment with rituximab attracted attention after a small, placebo-controlled study (30 patients) suggested beneficial effects (43). There was, however, no effect on the primary endpoint, the results have so far not been reproduced, and the risk of adverse effects is unclear. Reported adverse effects of rituximab in other contexts (such as neutropenia and infections) give reason for caution (44).

We believe the evidence base for cognitive behavioural therapy is so solid that all patients with chronic fatigue syndrome/myalgic encephalomyelitis should be offered this treatment. The sickest patients are often bedridden in darkened rooms. This can have serious physical and mental consequences over time (45, 46). We therefore believe that cognitive behavioural therapy must also be attempted in this subgroup, even though the evidence base is weaker. The minimal risk of adverse effects suggests that failing to treat the most severely ill patients is more risky than providing such treatment.

Debate – dualism and scientific abdication

Chronic fatigue syndrome/myalgic encephalomyelitis is a favourite topic of debate (47, 48). One frequent assertion is that the condition must be understood as a «biomedical» disease and that «psychosomatic accounts» – including studies that show efficacy of cognitive behavioural therapy – are not credible. Contributions are often emotionally charged and employ specific rhetorical devices in an attempt to weaken others’ professional credibility and right to express an opinion. The debate in many other countries follows a similar pattern and can acquire a tone that deters key professionals from expressing themselves in public (49).

Here, we will draw attention to two key features of the debate. First: Many debaters seem to think that physical and mental processes are distinct entities – it is assumed that a disease can be classified as either «physical» or «mental». This dualistic understanding has been largely rejected in modern neurobiology (50) and is also refuted by numerous empirical observations. Some examples: Acute mental stress (such as a death in the immediate family) can cause stress cardiomyopathy (51). Post-traumatic stress disorder produces a systemic inflammatory response (52). Chronic psychological stressors are associated with reduced NK cell function (53).

This has the following important consequence with regard to chronic fatigue syndrome/myalgic encephalomyelitis: Evidence of immunological changes cannot disprove the hypothesis that neurobiological processes are central to disease pathophysiology, quite the opposite in fact. Given the existence of a «fatigue alarm», it would be remarkable if altered immune responses were not seen. Likewise, the discovery of activated microglia in the brains of patients with chronic fatigue syndrome/myalgic encephalomyelitis (54) cannot be taken as evidence that the disease has a «biomedical» cause (48). Microglial activation is also seen in mental disorders and in response to chronic psychosocial stress (55). Such activation is thus to be expected in chronic fatigue syndrome/myalgic encephalomyelitis.

Second: The debate does not follow established norms for the exchange of professional opinions. The requirement to provide evidence of the efficacy of treatments is disregarded, in favour of media campaigns (56). Academics in senior scientific positions arrogantly express their opinions about a subject of which they have neither clinical nor scientific experience, while the reader is not informed about conflicts of interest (47, 48). This is an abdication of science responsibility. In the event that the chronic fatigue syndrome/myalgic encephalomyelitis field becomes a battleground of differing opinions – promoted with rhetorical devices – we will have given up on finding scientific truths.

An engaged and critical exchange of views is part of the scientific process and should of course be welcomed, but it must follow the established rules. This includes an intention to actually seek out the truth – not simply to triumph over your opponent. It is only the truth that can benefit patients.

References
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Chronic fatigue syndrome/myalgic encephalo-myelitis – pathophysiology, diagnosis and treatment, by V B Wyller, S E Reme, T E Mollnes in Tidsskr Nor Legeforen 2015; 135:2172 – 5

 

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Interview with Dr Judy Mikovits: a medical whistleblower’s tale

Posted on 01/04/2016 by wames

Global Freedom Movement video interview: Drugs, Disease and Deception: A Medical Whistleblower’s Tale with Judy Mikovits Phd

Meet Dr. Judy Mikovits, a passionate research molecular biologist and biochemist; wrongfully jailed with her career destroyed forever because she dared to publish findings unacceptable to vested interests.

Back story: On July 22, 2009, a special meeting was held with twenty-four leading scientists at the National Institutes of Health to discuss early findings that a newly discovered retrovirus was linked to chronic fatigue syndrome (CFS), prostate cancer, lymphoma, and eventually neurodevelopmental disorders in children. When Dr. Judy Mikovits finished her presentation the room was silent for a moment, then one of the scientists said, “Oh my God!”

The resulting investigation would be like no other in science.

For Dr. Mikovits, a twenty-year veteran of the National Cancer Institute, this was the midpoint of a five-year journey that would start with the founding of the Whittemore-Peterson Institute for Neuro-Immune Disease, and end with her as a witness for the federal government against her former employer, Harvey Whittemore, for illegal campaign contributions to Senate Majority Leader Harry Reid.

On this journey Dr. Mikovits would face the scientific prejudices against CFS, wander into the minefield that is autism, and through it all struggle to maintain her faith in God and the profession to which she had dedicated her life. This is a story for anybody interested in the peril, promise, and corruption of science at the very highest levels.

In this week’s interview of GFM Media, we will discuss, among other things, how prominent journals like Nature, Cell, and Science are damaging science. Case in point: the day before receiving the 2013 Nobel Prize in Medicine, Dr. Randy Schekman published a piece in The Guardian newspaper in which he declared his intention to never submit another piece of research to the journals, Science, Cell, Nature, and others like them because they are not serving the best interests of humanity and society.

Judy A. Mikovits has spent her life training to be a research scientist to honor her grandfather who died of cancer when she was a teenager. Dr. Mikovits earned her BA from University of Virginia and PhD in Biochemistry and Molecular Biology from George Washington University. In her 35-year quest to understand and treat chronic diseases, she has studied immunology, natural products chemistry, epigenetics, virology and drug development. In just over twenty years she rose from an entry-level lab technician to become director of the lab of Antiviral Drug Mechanisms at the National Cancer Institute before leaving to direct the Cancer Biology program at EpiGenX Pharmaceuticals in Santa Barbara California.

Judy Mikovits’ revelations around tainted vaccines and contaminated blood have caused shockwaves that resulted in the censoring and suppression of her work, and smearing of her character. Tonight, we look to discover why.

Having spent the last four years defending herself against bogus charges, whilst enduring four years of forced silence due to a court-ordered gag order, Judy’s life and career have changed forever, yet she continues to speak the truth.

Watch the video interview

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Pregabalin has positive effect on FM symptoms

Posted on 01/04/2016 by wames

Research abstract:

Pregabalin, an approved treatment for fibromyalgia (FM), has been shown to decrease sympathetic nervous system (SNS) activity and inhibit sympathetically maintained pain, but its effects on exercise responses have not been reported.

Methods: Using a randomized double-blind crossover design, we assessed the effect of 5 weeks of pregabalin (versus placebo) on acute cardiovascular and subjective responses to moderate exercise in 19 FM patients. Blood pressure (BP), heart rate (HR), and ratings of perceived exertion (RPE) during exercise and ratings of pain, physical fatigue, and mental fatigue before, during, and for 48 hours after exercise were compared in patients on pregabalin versus placebo and also versus 18 healthy controls.

Results: On placebo, exercise RPE and BP were significantly higher in FM patients than controls. Pregabalin responders, (defined by patient satisfaction and symptom changes) had significantly lower exercise BP, HR, and RPE on pregabalin versus placebo and no longer differed from controls.

Effect of Pregabalin on Cardiovascular Responses to Exercise and Postexercise Pain and Fatigue in Fibromyalgia: A Randomized, Double-Blind, Crossover Pilot Study
Andrea T. White, Kathleen C. Light, Lucinda Bateman, Ronald W. Hughen, Timothy A. Vanhaitsma, and Alan R. Light in Pain Research and Treatment, Volume 2015

 

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New year greetings from WAMES

Posted on 12/31/2015 by wames

New year greetings from the WAMES team. We hope you had the Christmas you needed and we wish you a healthier, happier, safe and dry 2016!

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Factors associated with chronic pain & fatigue in general public

Posted on 12/28/2015 by wames

Research abstract:

Highlights:

  • Chronic widespread pain and chronic fatigue commonly co-occur, share similar risk factors and are considered by some to be part of the same disorder.
  • In this study not all putative associated factors were commonly associated with both disorders.
  • The apparent common association appeared to be explained by the presence of common psychiatric disorders, anxiety and depression.

Objective

Chronic widespread pain and chronic fatigue share common associated factors but these associations may be explained by the presence of concurrent depression and anxiety.

Methods

We mailed questionnaires to a randomly selected sample of people in the UK to identify participants with chronic widespread pain (ACR 1990 definition) and those with chronic fatigue. The questionnaire assessed sociodemographic factors, health status, healthcare use, childhood factors, adult attachment, and psychological stress including anxiety and depression. To identify persons with unexplained chronic widespread pain or unexplained chronic fatigue; we examined participant’s medical records to exclude medical illness that might cause these symptoms.

Results

Of 1443 participants (58.0% response rate) medical records of 990 were examined. 9.4% (N = 93) had unexplained chronic widespread pain and 12.6% (N = 125) had unexplained chronic fatigue. Marital status, childhood psychological abuse, recent threatening experiences and other somatic symptoms were commonly associated with both widespread pain and fatigue.

No common effect was found for few years of education and current medical illnesses (more strongly associated with chronic widespread pain) or recent illness in a close relative, neuroticism, depression and anxiety scores (more strongly associated with chronic fatigue). Putative associated factors with a common effect were associated with unexplained chronic widespread pain or unexplained chronic fatigue only when there was concurrent anxiety and/or depression.

Discussion

This study suggests that the associated factors for chronic widespread pain and chronic fatigue need to be studied in conjunction with concurrent depression/anxiety. Clinicians should be aware of the importance of concurrent anxiety or depression.

Common and unique associated factors for medically unexplained chronic widespread pain and chronic fatigue, by J. McBeth, B. Tomenson, C.A. Chew-Graham, G.J. Macfarlane, J. Jackson, A. Littlewood, F.H. Creed in J Psychosom Res, 2015 Dec; 79(6): 484-91

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Group based self-management programme in Norway

Posted on 12/22/2015 by wames

Research abstract:

OBJECTIVE: To evaluate the effectiveness of a group-based self-management program for people with chronic fatigue syndrome.

DESIGN: A randomized controlled trial.

SETTING: Four mid-sized towns in southern Norway and two suburbs of Oslo.

SUBJECTS: A total of 137 adults with chronic fatigue syndrome.

INTERVENTION: A self-management program including eight biweekly meetings of 2.5 hours duration. The control group received usual care.

MAIN MEASURES: Primary outcome measure: Medical Outcomes Study-Short
Form-36 physical functioning subscale.

SECONDARY OUTCOME MEASURES: Fatigue severity scale, self-efficacy scale, physical and mental component summary of the Short Form-36, and the illness cognition questionnaire (acceptance subscale). Assessments were performed at baseline, and at six-month and one-year follow-ups.

RESULTS: At the six-month follow-up, a significant difference between the two groups was found concerning fatigue severity (p = 0.039) in favor of the control group, and concerning self-efficacy in favor of the intervention group (p = 0.039). These significant differences were not sustained at the one-year follow-up. No significant differences were found between the groups concerning physical functioning, acceptance, and health status at any of the measure points. The drop-out rate was 13.9% and the median number of sessions attended was seven (out of eight).

CONCLUSIONS: The evaluated self-management program did not have any sustained effect, as compared with receiving usual care.

Effectiveness of a group-based self-management program for people with chronic fatigue syndrome: A randomized controlled trial, by Pinxsterhuis I, Sandvik L, Strand EB, Bautz-Holter E, Sveen U in Clin Rehabil. 2015 Dec 16. pii: 0269215515621362. [Epub ahead of print]

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TRYCATS in CFS, Alzheimer’s disease and schizophrenia

Posted on 12/22/2015 by wames

Article abstract:

Many if not all chronic medical, neurodegenerative and neuroprogressive illnesses are characterised by chronic immune activation, oxidative and nitrosative stress (O&NS) and systemic inflammation. These environmental factors notably elevated pro-inflammatory cytokines activate indoleamine 2,3-dioxygenase (IDO) leading to an upregulated tryptophan catabolite (TRYCAT) pathway of tryptophan degradation in the periphery and in the brain.

In such conditions the TRYCAT pathway becomes the predominant system for tryptophan degradation in all body compartments. In this paper we review the pathways whereby TRYCATs may play a role in neuro-inflammatory and neuroprogressive disease. Thus chronic activation of the TRYCAT pathway leads to the production of a range of neuroactive, neuroprotective and neurotoxic TRYCATs.

Some TRYCATs such as quinolinic acid act as potent neurotoxins which inhibit ATP production by mitochondria, provoke increases in O&NS, disrupt neuron glial communication and blood brain barrier integrity, induce apoptosis of glial cells, directly damage neurons and function as a N-methyl D-aspartate (NMDA) receptor agonist.

Other TRYCATs such as kynurenic acid function as antagonists of NMDA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and kainate receptors and act to regulate levels of glutamate and dopamine. The neuroprotective functions of this TRYCAT are likely exercised via engagement with alpha7 nicotinic acetylcholine and aryl hydrocarbon receptors but the neuroprotective effects stemming from elevated kynurenic acid levels come at the price of severely compromised neurocognitive function and emotional processing.

Other TRYCATS also possess neurotoxic or neuroprotective properties via pro-oxidant and antioxidant effects. Here we discuss the involvement of the abovementioned TRYCAT pathways in schizophrenia, Alzheimer’s disease and chronic fatigue syndrome.

The many neuroprogressive actions of tryptophan catabolites (TRYCATs) that may be associated with the pathophysiology of neuro-immune disorders, by Morris G, Carvalho A, Anderson G, Galecki P, Maes M in Curr Pharm Des. 2015 Dec 14. [Epub ahead of print]

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Lucy’s practical ways to show compassion to someone who is continually ill

Posted on 12/22/2015 by wames

Telegraph article: Living with chronic fatigue: How I wish my friends would treat me, by Lucy Mayhew , 21 December 2015.

Lucy Mayhew_pre-illness

Bear Grylls and I have virtually nothing in common – the survival expert has a GTI turbo-charged body, whereas seven years ago, mine became my jailor.

Grylls recently name-checked  kindness as an overlooked quality “critical to survival,” and in the midst of paralysing physical pain, fear and despair I have learned how true this observation is. But also, because compassion doesn’t cure suffering, it is absurdly easy to neglect precisely when it is most urgently needed.

In 2008 I was in my twenties living in London leading a busy, fulfilling life working as a journalist, surrounded by a large circle of friends. Then an atomic bomb exploded wiping out virtually all physical function and destroying my life.

There is no tidy diagnosis or cure for my complex immune and gastrointestinal condition. It has most in common with the severest cases of Chronic Fatigue Syndrome where, as immunologist and AIDS and CFS specialist Dr Nancy Klimas explains, “patients experience a level of disability equal to that of patients with late-stage AIDs”.

A few weeks ago leading scientists around the world met at a global compassion conference in Shrewsbury where plans were unveiled for a new research institute dedicated to study and application of compassion.

The International Institute for the Study of Compassion has the support of Charles Darwin’s descendants. His great-great-granddaughter, Ruth Padel was at the conference where she spoke enthusiastically about the growing body of evidence that build’s on Darwin’s observations that compassionate behaviours are critical for human flourishing and even our very survival as a species.

Dr James Doty, a Stanford University neurosurgeon, also at the conference, highlighted research demonstrating compassion – and its kindred traits of understanding, kindness and connection – settles fear at a physiological level. My own experience attests to this. But I also know that our aversion to suffering leads us to denial – ‘she looks fine she must be just depressed’- or to reject, because we can’t stand to witness someone on a treadmill of suffering.

My circumstances are neither as cruel nor visible as those countless others are forced to endure. Nonetheless life has ceased to be life; rather it is an endless round of endurance I yearn to escape.

St Augustine said that physical pain was the greatest evil and he was right. I didn’t have a humour bypass or decide it might be diverting to become a hermit for almost a decade. I am extremely fond of life but this version needs returning to sender.

My illness has left me totally unable to speak due to a chronically sore throat. And the annihilating exhaustion which is impossible to describe, keeps me almost permanently in bed, often too weak to sit up. My gastric condition frequently delivers attacks which prevent eating for days.  I have cardiac and neurological symptoms and excruciating migraines but nothing breaks me like my seventy-two hour gut pain attacks which not even opiate pain medication can sate.

“Today I am sicker than ever and am currently casting about for viable medical help. Two things keep me going: stubborn determination that there is a path to recovery and savouring small gifts of compassion.”

I have worked with practitioners of conventional, alternative and integrated medicine based on every continent bar Africa and encountered kind, bullying and indifferent consultants. I’ve taken cannabis juice, cannabis suppositories; undertaken stool transplants; been brought to my knees by the side-effects of conventional and holistic medications. I’ve seen shamans and charlatans; tried to invent past lives; get good at meditation and coax forth a belief in God or the power of my own mind in an attempt to heal myself.

Today I am sicker than ever and am currently casting about for viable medical help. Two things keep me going: stubborn determination that there is a path to recovery and savouring small gifts of compassion.

Last week, in response to sharing my current state, my dearest friend emailed: “Nothing to say as all words, advice or sympathy from all parties are useless at this stage, but thanks for the update nonetheless.”

My friend is not callous, we adore each other and she wants me well but, as Dr Doty, concedes, being “truly compassionate when someone is suffering takes an immense amount of strength”.

Loss of physical function is hell but acute pain takes you to hell’s basement where you doubt life, goodness and yourself.  Alone, one employs legion strategies to keep buoyant.  Nothing, however, is as effective as the faith drawn from another’s warmth – it wards off desolation and revives one’s resolve to keep fighting.

The reply I sent my friend was to urge her that her input is never without value. I explained that the single, stand-out moment of my seven year illness was last November. She was visiting on the third day of one of my suicide-inducing gastric pain attacks.

‘You came into my room,’ I wrote. ‘As I cried you hugged me and said you knew what a huge amount I had done and how endlessly hard I had been trying to find a path back to health. That explicit recognition of the breadth and depth of my delving and the connected salute to how vile this situation was, did more good than anything else could possibly have done. It didn’t stop the pain or banish the fear but it helped. A lot. It’s what people mean when they talk about bearing testimony to a person’s suffering. It transcends pity. It’s love as understanding which is priceless.

Sometimes there are no viable suggestions but you can repeatedly let a person in distress know you are holding the space for brighter times for them. It never gets old or tired. It never becomes unnecessary. It can be spoken and unspoken — both is best.

“We may be unable to affect the outcome of a hellish circumstance, but the way it is experienced can always be altered and improved.”

Strip a person of everything they have and they will be left with two things — the instinct to survive, and the instinct of love, both given and received.

Philosopher A.C Grayling calls love ‘a baggy concept’, but its very roominess allows it to be expressed and experienced in a hundred different ways. Such caring does not require grand gestures, special gifts, and it doesn’t need to impinge on the day of a busy person, but it does need showing.

Eleanor Roosevelt also suggested the shortness of life meant it was a good idea to learn from other people’s mistakes. So I am sharing these hard-learned, unoriginal reflections in case some of their sentiment might imprint and suffuse where pithier, more eloquent words may only fleetingly register.

So whenever you might be faced with a situation where you feel useless, remind yourself this isn’t so. A legitimately frightened person knows they cannot look to another for rescue but they will be soothed, albeit imperceptibly, by small bids of solidarity. We may be unable to affect the outcome of a hellish circumstance, but the way it is experienced can always be altered and improved.

If a person is alive, they will still have hope because hope is an instinct. Even the condemned man being marched to his execution has hope of a last-minute reprieve; so if he knows that someone else also holds that hope, and, at the very least, wishes the circumstances were different, that helps; so much. Believe me.

Five practical ways to show compassion to someone who is continually ill

  1. Be patient and constant: Like regular meals, a person in distress needs repeated comfort and, as time passes, that need intensifies. It is human nature to hold on to hope even when the outlook looks pretty futile; and to feel that someone else cares and is holding on too is a great tonic.
  2. Share your life: Visits and phone-calls aren’t always possible but record a voice message on your smartphone or send a chatty email – these can light up the world for days. Don’t worry how pedestrian or dull you think your news is because it’s the inclusion – the human connection – that’s cherished. Likewise an out of the blue, three-word text: ‘thinking of you,’ can really lift a pain-filled day.
  3. Be sensitive: We still want to hear your happy news – engagements, pregnancies, career successes, as well as your problems, even if they seem trifling. A short simple acknowledgement of how hard it must also be to be denied the joys (and trials) of ordinary life, shows sensitivity that deeply nourishes.
  4. Avoid belittling commentary: ‘I wish you’d try to overcome this depression; get some fresh air; ignore the pain. You certainly look well.’  Implying this is a chosen circumstance that stems from weakness, lack of willpower and moral fibre, hurts. When quality of life is so diminished there is nothing one won’t do to feel well.
  5. Show you believe: Pain and poorly understood illnesses are frequently stigmatised and discredited. Simply naming the presence of  suffering brings enormous relief, as does a sympathetic smile or hand on the arm. The confidence arising from your acknowledgement also provides space for lightness and laughter.
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Changes in gut & plasma microbiome following exercise challenge in ME/CFS

Posted on 12/21/2015 by wames

Research abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disease characterized by intense and debilitating fatigue not due to physical activity that has persisted for at least 6 months, post-exertional malaise, unrefreshing sleep, and accompanied by a number of secondary symptoms, including sore throat, memory and concentration impairment, headache, and muscle/joint pain. In patients with post-exertional malaise, significant worsening of symptoms occurs following physical exertion and exercise challenge serves as a useful method for identifying biomarkers for exertion intolerance.

Evidence suggests that intestinal dysbiosis and systemic responses to gut microorganisms may play a role in the symptomology of ME/CFS. As such, we hypothesized that post-exertion worsening of ME/CFS symptoms could be due to increased bacterial translocation from the intestine into the systemic circulation.

To test this hypothesis, we collected symptom reports and blood and stool samples from ten clinically characterized ME/CFS patients and ten matched healthy controls before and 15 minutes, 48 hours, and 72 hours after a maximal exercise challenge. Microbiomes of blood and stool samples were examined.

Stool sample microbiomes differed between ME/CFS patients and healthy controls in the abundance of several major bacterial phyla. Following maximal exercise challenge, there was an increase in relative abundance of 6 of the 9 major bacterial phyla/genera in ME/CFS patients from baseline to 72 hours post-exercise compared to only 2 of the 9 phyla/genera in controls (p = 0.005). There was also a significant difference in clearance of specific bacterial phyla from blood following exercise with high levels of bacterial sequences maintained at 72 hours post-exercise in ME/CFS patients versus clearance in the controls.

These results provide evidence for a systemic effect of an altered gut microbiome in ME/CFS patients compared to controls. Upon exercise challenge, there were significant changes in the abundance of major bacterial phyla in the gut in ME/CFS patients not observed in healthy controls. In addition, compared to controls clearance of bacteria from the blood was delayed in ME/CFS patients following exercise.

These findings suggest a role for an altered gut microbiome and increased bacterial translocation following exercise in ME/CFS patients that may account for the profound post-exertional malaise experienced by ME/CFS patients.

Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, (ME/CFS), by Sanjay K. Shukla, Dane Cook, Jacob Meyer, Suzanne D. Vernon, Thao Le, Derek Clevidence, Charles E. Robertson, Steven J. Schrodi, Steven Yale, Daniel N. Frank in PLOS One, 10(12) December 18, 2015

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