Treating Medically Unexplained Symptoms via Improving Access to Psychological Therapy (IAPT): major limitations identified

Posted on 02/10/2020 by wames

Treating medically unexplained symptoms via improving access to psychological therapy (IAPT): major limitations identified, by Keith Geraghty, Michael J Scott in BMC Psychology Vol 8, #1, p 13, February 5, 2020

 

Research abstract:

Background:

Improving Access to Psychological Therapies is a UK Government funded initiative to widen access to psychological treatment for a range of common mental health complaints, such as depression and anxiety. More recently, the service has begun to treat patients with medically unexplained symptoms.

This paper reports on a review of treatment protocols and early treatment data for medically unexplained symptoms, specifically the illness myalgic encephalomyelitis/ chronic fatigue syndrome.

Main text:

A series of seven core problems and failings are identified, including an unproven treatment rationale, a weak and contested evidence-base, biases in treatment promotion, exaggeration of recovery claims, under-reporting of drop-out rates, and a significant risk of misdiagnosis and inappropriate treatment.

Conclusions:

There is a pressing need for independent oversight of this service, specifically evaluation of service performance and methods used to collect and report treatment outcomes. This service offers uniform psycho-behavioural therapy that may not meet the needs of many patients with medically unexplained health complaints.

Psychotherapy should not become a default when patients’ physical symptoms remain unexplained, and patients should be fully informed of the rationale behind psychotherapy, before agreeing to take part. Patients who reject psychotherapy or do not meet selection criteria should be offered appropriate medical and psychological support.

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A machine learning approach to the differentiation of fMRI data of CFS from a sedentary control

Posted on 02/10/2020 by wames

A machine learning approach to the differentiation of Functional Magnetic Resonance Imaging data of Chronic Fatigue Syndrome (CFS) from a sedentary control, by Destie Provenzano,  Stuart D Washington and  James N Baraniuk in Front. Comput. Neurosci., 29 January 2020 [https://doi.org/10.3389/fncom.2020.00002]

 

Chronic Fatigue Syndrome (CFS) is a debilitating condition estimated to impact at least 1 million individuals in the United States, however there persists controversy about its existence.

Machine learning algorithms have become a powerful methodology for evaluating multi-regional areas of fMRI activation that can classify disease phenotype from sedentary control. Uncovering objective biomarkers such as an fMRI pattern is important for lending credibility to diagnosis of CFS.

fMRI scans were evaluated for 69 patients (38 CFS and 31 Control) taken before (Day 1) and after (Day 2) a submaximal exercise test while undergoing the n-back memory paradigm. A predictive model was created by grouping fMRI voxels into the Automated Anatomical Labeling (AAL) atlas, splitting the data into a training and testing dataset, and feeding these inputs into a logistic regression to evaluate differences between CFS and control.

Model results were cross-validated 10 times to ensure accuracy. Model results were able to differentiate CFS from sedentary controls at a 80% accuracy on Day 1 and 76% accuracy on Day 2 (Table 3). Recursive features selection identified 29 ROI’s that significantly distinguished CFS from control on Day 1 and 28 ROI’s on Day 2 with 10 regions of overlap shared with Day 1 (Figure 3). These 10 shared regions included the putamen, inferior frontal gyrus, orbital (F3O), supramarginal gyrus (SMG), temporal pole; superior temporal gyrus (T1P) and caudate ROIs.

Figure 3. Significantly elevated BOLD activity during the 2 > 0 back condition in CFS and control groups before and after exercise

Figure 3. Significantly elevated BOLD activity during the 2 > 0 back condition in CFS and control groups before and after exercise

This study was able to uncover a pattern of activated neurological regions that differentiated CFS from Control. This pattern provides a first step toward developing fMRI as a diagnostic biomarker and suggests this methodology could be emulated for other disorders. We concluded that a logistic regression model performed on fMRI data significantly differentiated CFS from Control.

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Post-exertional malaise is associated with greater symptom burden & psychological distress in patients diagnosed with CFS

Posted on 02/10/2020 by wames

Post-exertional malaise is associated with greater symptom burden and psychological distress in patients diagnosed with Chronic Fatigue Syndrome, by Marcella May, Sara F Milrad, Dolores M Perdomo, Sara J Czaja, Mary Ann Fletcher, Devika R Jutagir, Daniel L Hall, Nancy Klimas, Michael H Antoni in Journal of Psychosomatic Research, Volume 129, February 2020, [doi.org/10.1016/j.jpsychores.2019.109893]

 

Highlights

  • Patients high in PEM endorse greater symptom burden than those low in PEM
  • Patients high in PEM endorse greater psychological adversity than those low in PEM
  • Results suggest the Fukuda case definition does not define a heterogeneous group
  • PEM may identify patients who would most benefit from psychological intervention

Research abstract:

Objective:
Post-exertional malaise (PEM) is often considered a cardinal symptom of Chronic Fatigue Syndrome (CFS). There is no gold standard diagnostic method for CFS, however, and the Centers for Disease Control (CDC) Fukuda case definition does not require PEM. Research has identified differences in symptom burden between patients according to PEM, but whether it is associated with psychological distress has not been investigated.

Methods:
The CDC CFS Inventory, Fatigue Symptom Inventory, Profile of Mood States, Center for Epidemiologic Studies Depression Scale, Perceived Stress Scale, and subscales of the Sickness Impact Profile were administered to 261 patients diagnosed with the Fukuda criteria. PEM status (loPEM/hiPEM) was determined via self-reported post-exertional fatigue severity. Analyses of covariance (ANCOVA), controlling for age and gender, assessed cross-sectional group differences, and cross-sectional linear regressions using the continuous PEM severity predictor paralleled these analyses.

Results:
hiPEM patients reported greater symptom intensity, frequency, and interference than loPEM counterparts (p’s < .001). hiPEM patients also reported greater social disruption, depressive symptoms, and mood disturbance (p’s ≤ .011). Groups did not differ in recent negative life experiences, perceived stress, or demographic variables. The results of regression analyses mirrored those of ANCOVAs.

Conclusion:
This study replicates the association between PEM and symptom burden and additionally associates PEM with psychological distress; psychological distress could, however, be a consequence of symptom burden. Differences between hiPEM and loPEM CFS patients highlight the heterogeneity of diagnoses resulting from the Fukuda criteria. It is also possible that PEM identifies particularly distressed patients for whom psychological intervention would be most beneficial.

Pre-proof full paper

Virology blog: Trial By Error: PEM Is Bad and So Is Fukuda, New Study Finds,
24 December 2019, By David Tuller     Excerpt:

So as far as I can tell, the main message of this paper is, or should be, that the Fukuda case definition is inadequate because many of those who meet it do not appear to experience PEM as a debilitating factor, if they experience it at all. Given that PEM is already viewed as the cardinal symptom of the illness, the logical conclusion is that such patients don’t have ME, despite having been diagnosed with CFS per Fukuda. As it reads, the study’s main finding seems to be that CFS patients with PEM need psychological intervention—when in fact what they really need most is effective medical treatments for their ME.

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An adrenalectomy mouse model reflecting clinical features for CFS

Posted on 02/06/2020 by wames

An adrenalectomy mouse model reflecting clinical features for Chronic Fatigue Syndrome, by  Jin-Seok Lee, Yoo-Jin Jeon, Samuel-Young Park and Chang-Gue Son in Biomolecules 2020, 10(1), 71; [https://doi.org/10.3390/biom10010071] (This article belongs to the Special Issue Inflammation as Target treatment for Chronic Diseases)

 

Research abstract:

Chronic fatigue syndrome (CFS) is one of the most intractable diseases and is characterized by severe central fatigue that impairs even daily activity. To date, the pathophysiological mechanisms are uncertain and no therapies exist. Therefore, a proper animal model reflecting the clinical features of CFS is urgently required.

We compared two CFS animal models most commonly used, by injection with lipopolysaccharide (LPS from Escherichia coli O111:B4) or polyinosinic: polycytidylic acid (poly I:C), along with bilateral adrenalectomy (ADX) as another possible model. Both LPS- and poly I:C-injected mice dominantly showed depressive behaviors, while ADX led to fatigue-like performances with high pain sensitivity.

In brain tissues, LPS injection notably activated microglia and the 5-hydroxytryptamine (HT)1A receptor in the prefrontal cortex and hippocampus. Poly I:C-injection also remarkably activated the 5-HT transporter and 5-HT1A receptor with a reduction in serotonin levels in the brain. ADX particularly activated astrocytes and transforming growth factor beta (TGF-β) 1 in all brain regions.

Our results revealed that LPS and poly I:C animal models approximate depressive disorder more closely than CFS. We suggest that ADX is a possible method for establishing a mouse model of CFS reflecting clinical features, especially in neuroendocrine system.

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Welsh Government proposes new advisory group for ME/CFS & pain

Posted on 02/06/2020 by wames

New Welsh Government Advisory Group for ME/CFS and pain

 

2014 Task & Finish Group Report

It is five years since the Welsh Government published a Task & Finish Report giving Health Boards an action plan for improving services for ME/CFS and Fibromyalgia.

WAMES has been a member of the national advisory group for the T&FG Report – the All Wales Implementation Group (AWIG) – which has met 4 times a year with representatives from Health Boards and government.

WAMES has also been actively challenging individual Health Boards to implement the recommendations, with little success. Health Boards have repeatedly ignored calls from patients and government to take ME service planning seriously.

New advisory group

The Welsh Government has now decided to take a different approach and merge three groups (Persistent Pain, Arthritis and ME/CFS and FM) into one advisory group. The aim will be to report to the Chief Medical Officer on issues the conditions share and bespoke issues relating to specific conditions. Established channels of communication will then be used to engage with Health Boards.

It is hoped the new group will be established by April 2020 and the new structure will be monitored for effectiveness after sufficient time has passed.

In addition Health Education and Improvement Wales (HEIW) will be in attendance at the new group so they understand the issues surrounding education, training and workforce development.

The Welsh Government research and development team – Health and Care Research Wales –  have confirmed funding is available for well designed research projects.

Patient representation

WAMES has questions about whether this new group will be more effective in enlisting Health Board commitment to providing care for people with ME than previous approaches, but we are pleased that the Welsh Government recognises the need to find a better way of working.

Kevin Francis, the Policy lead for ME in the Welsh Government is happy to meet with groups who support people living with ME, FM and pain conditions. He wishes to better understand the issues for those living with these conditions.  Please let Jan know if you wish to take up this offer. jan@wames.og.uk

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Conceptualising illness & disease: reflections on Sharpe & Greco

Posted on 02/06/2020 by wames

Conceptualising illness and disease: reflections on Sharpe and Greco (2019), by Carolyn Wilshire , Tony Ward in BMJ …Medical Humanities [Published Online First: 11 December 2019] doi: 10.1136/medhum-2019-011756

 

Article abstract:

In a recent paper, Sharpe and Greco suggest that chronic fatigue syndrome/myalgic encephalomyelitis (MECFS) can be viewed as an instance of “illness without disease”, and consequently, treatment should be directed towards altering the patient’s experience of, and response to, their symptoms.

We discuss two broad issues that arise from Sharpe and Greco’s article, one relating to the assumptions they make about MECFS and its treatment specifically, and the other relating to their conceptualisation of the illness/disease dichotomy. We argue that the term “illness without disease”, in the sense that Sharpe and Greco use it, is problematic because it can lead to unwarranted causal assumptions.

Following these critical comments, we present a new framework for conceptualising the relationship between explanatory disease models and the experience of illness.

Read full paper

Excerpt:

We have argued here that, in medicine, it is not appropriate to make claims about causation on the basis of non-specific observations, in which direction of causation has not been clearly established, or simply because there is a lack of anything better.17

Causal claims that are phrased at a psychological level of description need to be subjected to the same tests as any other causal claim.

Treatments founded on unsubstantiated claims—even psychological ones—can do harm, no matter how well intentioned they are.  Even if patients are not directly harmed by the treatment, they may bear other costs. For example, they may feel personally responsible if they fail to recover. Also, any concerns they do raise may be dismissed, or even caricatured.

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Cell danger response biology – the new science that connects environmental health with mitochondria & the rising tide of chronic illness

Posted on 02/04/2020 by wames

Perspective: Cell danger response biology the new science that connects environmental health with mitochondria and the rising tide of chronic illness, by Robert K Naviaux in Mitochondrion Vol 51, March 2020, Pages 40-45 [Available online 23 December 2019] https://doi.org/10.1016/j.mito.2019.12.005

 

Highlights

  • Mitochondria regulate the cell danger response (CDR) that controls innate immunity and healing.

  • Chemical pollutants in the environment lower the threshold for CDR activation.

  • Persistent activation of CDR inhibits healing and leads to chronic illness.

  • Metabolomics and exposomics can help guide new policies to lower the risk of chronic illness.

 

Research abstract:

This paper is written for non-specialists in mitochondrial biology to provide access to an important area of science that has broad implications for all people.

The cell danger response (CDR) is a universal response to environmental threat or injury. Once triggered, healing cannot be completed until the choreographed stages of the CDR are returned to an updated state of readiness. Although the CDR is a cellular response, it has the power to change human thought and behavior, child development, physical fitness and resilience, fertility, and the susceptibility of entire populations to disease.

Mitochondria regulate the CDR by monitoring and responding to the physical, chemical, and microbial conditions within and around the cell. In this way, mitochondria connect cellular health to environmental health.

Over 7,000 chemicals are now made or imported to the US for industrial, agricultural, and personal care use in amounts ranging from 25,000 to over 1 million pounds each year, and plastic waste now exceeds 83 billion pounds/year. This chemical load creates a rising tide of manmade pollutants in the oceans, air, water, and food chain. Fewer than 5% of these chemicals have been tested for developmental toxicity.

In the 1980s, 5–10% of children lived with a chronic illness. As of 2018, 40% of children, 50% of teens, 60% of adults under age 65, and 90% of adults over 65 live with a chronic illness. Several studies now report the presence of dozens to hundreds of manmade chemicals and pollutants in placenta, umbilical cord blood, and newborn blood spots.

Fig. 1. Chronic Health Disorders that have Increased 2-100 times since the 1980s

New methods in metabolomics and exposomics allow scientists to measure thousands of chemicals in blood, air, water, soil, and the food chain. Systematic measurements of environmental chemicals can now be correlated with annual and regional patterns of childhood illness. These data can be used to prepare a prioritized list of molecules for congressional action, ranked according to their impact on human health.

“When a deep injury is done to us, we never heal until we forgive.” -Nelson Mandela (1918-2013)

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Neuroinflammation, oxidative stress & neurogenesis in a mouse model of CFS, & the treatment with Kampo medicine

Posted on 02/03/2020 by wames

Neuroinflammation, oxidative stress, and neurogenesis in a mouse model of Chronic Fatigue Syndrome, and the treatment with Kampo medicine, by Qiang He, Mio Sawada, Naruhiro Yamasaki, Sumiyo Akazawa, Hisakazu Furuta, Hiroaki Uenishi, Xiangjin Meng, Takeshi Nakahashi, Yasuhito Ishigaki, Junji Moriya in Biological and Pharmaceutical Bulletin Vol 43 (2020) no. 1, pp 110-115 [DOI https://doi.org/10.1248/bpb.b19-00616]

 

Research abstract:

The diagnosis of chronic fatigue syndrome (CFS) is mainly symptom-based, and the etiology is still unclear. Here, we evaluated the pathological changes in the brain of a mouse model of CFS and studied the effects of Kampo medicine.

A mouse model of CFS was established through six repeated injections of Brucella abortus (BA) every two weeks for a period of 12 weeks. Neuroinflammation was measured by estimating interleukin (IL)-1β, IL-6, and interferon-gamma (IFN-γ), and oxidative stress by nitrotyrosine (3-NT) and 4-hydroxynonenal (4-HNE) 6 weeks after the last injection. Hippocampal neurogenesis was evaluated through Ki-67, doublecortin (DCX), and 5-bromodeoxyuridine (BrdU) assays.

The effects of Kampo medicines (Hochuekkito (TJ-41) and Hachimijiogan (TJ-7)) on neuroinflammation during CFS were studied. The wheel-running activity of mice was decreased by about 50% compared to baseline at 6 weeks after the last BA injection. The levels of IL-1β, IL-6, 3-NT, and 4-HNE were increased in both the cortex and the hippocampus of CFS mice at 6 weeks after the last BA injection. Hippocampal neurogenesis was unchanged in CFS mice. Treatment with TJ-41 and TJ-7 reduced the expressions of IL-1β, IL-6, and IFN-γ in the hippocampus but not in the cortex.

The results of the present study indicate that neuroinflammation and oxidative stress play important roles in the pathogenesis of CFS. The data further suggest that treatment with TJ-41 and TJ-7 could help reduce the inflammation associated with CFS in the hippocampus, but failed to improve the symptoms in CFS mice.

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Left out – a Norwegian documentary about ME & research

Posted on 02/02/2020 by wames

Left out – a documentary about ME

The documentary Left Out (De Bortgjemte) was shown on national TV in Norway in 2018 and now has its international release on YouTube with English subtitles, 29 January 2020.

Director Paul Schaathun followed some ME patients and Dr Oystein Fluge’s RituxME trial  for 2 years. The resulting film is both informative and touching.

When they realised she had ME they just let go of us. “Sorry, it’s ME, we can’t do any more. We had to fend for ourselves.                                  Anne Karen, Emile’s mother

Watch the film

 

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Comprehensive circulatory metabolomics in ME/CFS reveals disrupted metabolism of acyl lipids & steroids

Posted on 01/30/2020 by wames

Comprehensive circulatory metabolomics in ME/CFS reveals disrupted metabolism of acyl Lipids and steroids, by Arnaud Germain, Dinesh K Barupal, Susan M Levine and Maureen R Hanson in Metabolites 2020, 10(1), 34; 14 January 2020 [doi.org/10.3390/metabo10010034]

 

Research abstract:

The latest worldwide prevalence rate projects that over 65 million patients suffer from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), an illness with known effects on the functioning of the immune and nervous systems. We performed an extensive metabolomics analysis on the plasma of 52 female subjects, equally sampled between controls and ME/CFS patients, which delivered data for about 1750 blood compounds spanning 20 super-pathways, subdivided into 113 sub-pathways.

Statistical analysis combined with pathway enrichment analysis points to a few disrupted metabolic pathways containing many unexplored compounds. The most intriguing finding concerns acyl cholines, belonging to the fatty acid metabolism sub-pathway of lipids, for which all compounds are consistently reduced in two distinct ME/CFS patient cohorts.

We compiled the extremely limited knowledge about these compounds and regard them as promising in the quest to explain many of the ME/CFS symptoms. Another class of lipids with far-reaching activity on virtually all organ systems are steroids; androgenic, progestin, and corticosteroids are broadly reduced in our patient cohort.

We also report on lower dipeptides and elevated sphingolipids abundance in patients compared to controls. Disturbances in the metabolism of many of these molecules can be linked to the profound organ system symptoms endured by ME/CFS patients.

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