Obesity in adolescents with CFS

Posted on 09/29/2016 by wames

Research abstract:

Objective:
Identify the prevalence of obesity in patients with chronic fatigue syndrome (CFS) compared with healthy adolescents, and those identified with CFS in a population cohort.

Design:
Cross-sectional analysis of multiple imputed data.

Setting:
Data from UK paediatric CFS/myalgic encephalomyelitis (CFS/ME) services compared with data collected at two time points in the Avon Longitudinal Study of Parents and Children (ALSPAC).

Patients:
1685 adolescents who attended a CFS/ME specialist service between 2004 and 2014 and 13 978 adolescents aged approximately 13 years and 16 years participating in the ALSPAC study.

Main outcome measures:
Body mass index (BMI) (kg/m2), sex-specific and age-specific BMI Z-scores (relative to the International Obesity Task Force cut-offs) and prevalence of obesity (%).

Results:
Adolescents who had attended specialist CFS/ME services had a higher prevalence of obesity (age 13 years: 9.28%; age 16 years: 16.43%) compared with both adolescents classified as CFS/ME in ALSPAC (age 13 years: 3.72%; age 16 years: 5.46%) and those non-CFS in ALSPAC (age 13 years: 4.18%; age 16 years: 4.46%). The increased odds of obesity in those who attended specialist services (relative to non-CFS in ALSPAC) was apparent at both 13 years (OR: 2.31 (1.54 to 3.48)) and 16 years, with a greater likelihood observed at 16 years (OR: 4.07 (2.04 to 8.11)).

Conclusions:
We observed an increased prevalence of obesity in adolescents who were affected severely enough to be referred to a specialist CFS/ME service. Further longitudinal research is required in order to identify the temporal relationship between the two conditions.

Obesity in adolescents with chronic fatigue syndrome: An observational study, by T Norris, K Hawton, J Hamilton-Shield, E Crawley in Archives of Disease in Childhood
[Preprint September 21, 2016]

 

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Acceptance and commitment therapy (ACT) for CFS

Posted on 09/28/2016 by wames

Research abstract:

Background:
Acceptance is understood to be an important element in coping with chronic illnesses, linked to positive outcomes such as reduced symptoms and greater quality of life. Chronic Fatigue Syndrome (CFS) is a disabling syndrome that is associated with a poor reported quality of life even in comparison to other chronic conditions.

Given that Acceptance and Commitment Therapy (ACT) is a psychotherapeutic model aimed at increasing psychological flexibility, with an emphasis on experiential acceptance and the pursuit of values, this approach holds potential for living and coping with CFS.

Methods:
This study used a mixed method multiple single case design to explore the effects of
a six week self-help ACT intervention with six participants with CFS.

Results:
Significant increases in ‘engaged response style’ was replicated in four out of six
participants and maintained at follow up, with the qualitative data adding further
validity to the importance of the values component of the intervention. Low initial
acceptance scores improved in four participants but were not maintained. Overall
measures of psychological flexibility indicated improvements maintained at follow up
for three participants. All participants wearing the activity monitor showed increased
physical activity post-intervention, three of which maintained this at follow up. Five
participants reported less symptoms and disability, which was maintained for three
participants. The implicit measure indicated that underlying beliefs remained stable.

Conclusion:
This study was largely exploratory but it seems that this intervention might be of
benefit to some individuals with CFS, particularly in the promotion and pursuit of
individual values. This study adds support to the role of acceptance in CFS however
in this format at least it seems that any benefits from the intervention are difficult to
maintain. Although improvements in overall psychological flexibility were replicated in
three out of six participants, this prompts discussion about the ineffectiveness of the
intervention for other participants.

Acceptance and commitment therapy for Chronic Fatigue Syndrome: a case series approach, by Lauren Roche. DClinPsy thesis, University of Lincoln. 2 Sep 2016

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We are the #MillionsMissing

Posted on 09/27/2016 by wames

millions-missing-demand-change

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Cognitive processes research in CFS and cancer

Posted on 09/26/2016 by wames

Research abstract:

Background:
There is an abundance of research into cognitive processing biases in clinical psychology including the potential for applying cognitive bias modification techniques to assess the causal role of biases in maintaining anxiety and depression. Within the health psychology field, there is burgeoning interest in applying these experimental methods to assess potential cognitive biases in relation to physical health conditions and health-related behaviours. Experimental research in these areas could inform theoretical development by enabling measurement of implicit cognitive processes that may underlie unhelpful illness beliefs and help drive health-related behaviours.

However, to date, there has been no systematic approach to adapting existing experimental paradigms for use within physical health research. Many studies fail to report how materials were developed for the population of interest or have used untested materials developed ad hoc. The lack of protocol for developing stimuli specificity has contributed to large heterogeneity in methodologies and findings.

Purpose:
In this article, we emphasize the need for standardized methods for stimuli development and replication in experimental work, particularly as it extends beyond its original anxiety and depression scope to other physical conditions.

Method:
We briefly describe the paradigms commonly used to assess cognitive biases in attention and interpretation and then describe the steps involved in comprehensive/robust stimuli development for attention and interpretation paradigms using illustrative examples from two conditions: chronic fatigue syndrome and breast cancer.

Conclusions:
This article highlights the value of preforming rigorous stimuli development and provides tools to aid researchers engage in this process. We believe this work is worthwhile to establish a body of high-quality and replicable experimental research within the health
psychology literature.

Maximizing potential impact of experimental research into cognitive processes in health psychology: A systematic approach to material development, by Alicia M. Hughes, Rola Gordon, Trudie Chalder, Colette R. Hirsch, Rona Moss-Morris in British Journal of Health Psychology [Preprint September 22, 2016]

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A tool for making sense of health studies

Posted on 09/26/2016 by wames

Understanding Health Research: a tool for making sense of health studies

Can I trust the findings of health research?
This online tool aims to guide you through a series of questions to help you review health research.

The website also contains introductions to some important concepts and skills that you may find useful when making sense of health research e.g. sampling methods, bias.

The Understanding Health Research tool was developed by researchers at MRC/CSO Social and Public Health Sciences Unit, University of Glasgow, in collaboration with two other MRC Units and the London School of Hygiene and Tropical Medicine.

Let us know if you find this tool helpful.

 

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PACE trial shows patients need to scrutinise studies about their health,

Posted on 09/26/2016 by wames

BMJ blog post by Simon McGrath, 22 Sep 2016: PACE trial shows why medicine needs patients to scrutinise studies about their health

Like all patients, what I want most from clinical research is treatments that work, not ones that merely look good on paper. As The BMJ has pointed out, patients are often faced with over-hyped treatments and an incomplete research base biased towards positive results.

These biases arise partly because of “publish or perish” pressure on researchers. By contrast, patients’ only concern is to establish what really works: their interests are directly aligned with those of good science and sound medicine.

So, well informed patients should have the right to query research findings, and researchers should be willing to engage constructively and transparently with patients who challenge them.

Most aspects of my own illness, ME/CFS (chronic fatigue syndrome), are contentious, so there’s all the more reason to ensure that trial data are properly scrutinised. In ME/CFS, the PACE trial of cognitive behaviour therapy and graded exercise dominates the research landscape, so its findings matter—not least because of their influence on treatment guidelines around the world—but the findings are contested.

For years, patients have believed that the modest gains in subjective outcomes in this non-blinded trial were not matched by objective gains and that key analyses specified in the study’s original protocol were altered drastically once the trial was under way. Thresholds for “recovery” were lowered so far that 13% of patients already met the revised threshold for recovery of physical function before therapy.

Unfortunately, the trial authors have tended to dismiss rather than engage with the central issues. This led one patient to submit a freedom of information request for data that would allow the key outcomes to be analysed using the various thresholds specified in the trial’s original protocol. Queen Mary University of London, which holds the data, refused the request, but the Information Commissioner overruled it and, despite the university’s £245,000 appeal to a tribunal, the order to release the data was upheld. The tribunal determined that there was a strong public interest in data release.

In recent months many academics have publicly endorsed the concerns originally raised by patients, and they have acknowledged patients for bringing the issues to light (most notably in an open letter from 42 researchers). The help from these academics has been critical in securing data release and in raising the profile of the issues more generally.

Despite this progress, however, I’m deeply frustrated and saddened. Frustrated because, for many years, researchers and the medical establishment would not engage with patients who made the same criticisms—simply because, it seems, they were patients. And I’m saddened that an attempt to establish the truth about the effectiveness of the main interventions recommended for my disease ended up in a courtroom.

These issues are relevant well beyond ME/CFS and PACE. Researchers are not infallible, and their research reports are not the incontestable truth. Patients with any illness should be allowed to scrutinise findings from any clinical trial about their health. Disease strikes patients from all walks of life, including many who have or acquire the skills to competently assess research and who can contribute effectively to the science. We need a culture of open data, in which researchers engage with all reasonable criticism, whether from academics or patients.

Above all, what’s needed is to establish what truly works and what does not.

See also:

Freedom of information: can researchers still promise control of participants’ data?

Peter White et al: Releasing patient data from the PACE trial for chronic fatigue syndrome

Simon McGrath had an all too brief career in charity fundraising before becoming too ill to work in 1995. He has a biochemistry degree from the University of Oxford and occasionally blogs about ME/CFS research.

 

 

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Potential new way to sway the immune system

Posted on 09/23/2016 by wames

ME Global Chronicle article, by Madeline McCurry-Schmidt, Aug 2016  Found: A Potential New Way to Sway the Immune System (not specifically about ME)

A new international collaboration involving scientists at The Scripps Research Institute (TSRI) opens a door to influencing the immune system, which would be useful to boost the effectiveness of vaccines or to counter autoimmune diseases such as lupus and rheumatoid arthritis.

The research, published August 1, 2016, in The Journal of Experimental Medicine, focused on a molecule called microRNA-155 (miR-155), a key player in the immune system’s production of disease-fighting antibodies.

“It’s very exciting to see exactly how this molecule works in the body,” said TSRI Associate Professor Changchun Xiao, who co-led the study with Professor Wen-Hsien Liu of Xiamen University in Fuijan province, China.

An Immune System Tango
Our cells rely on molecules called microRNAs (miRNAs) as a sort of “dimmer switches” to carefully regulate protein levels and combat disease.

“People know miRNAs are involved in immune response, but they don’t know which miRNAs and how exactly,” explained TSRI Research Associate Zhe Huang, study co-first author with Liu and Seung Goo Kang of TSRI and Kangwon National University.

In the new study, the researchers focused on the roles of miRNAs during the critical period when the immune system first detects “invaders” such as viruses or bacteria. At this time, cells called T follicular helpers proliferate and migrate to a different area of the lymph organs to interact with B cells.

“They do a sort of tango,” said Xiao.  This interaction prompts B cells to mature and produce effective antibodies, eventually offering long-term protection against infection.
“The next time you encounter that virus, for example, the body can respond quickly,” said Xiao.

Identifying a Dancer
Using a technique called deep sequencing, the team identified miR-155 as a potential part of this process. Studies in mouse models suggested that miR-155 works by repressing a protein called Peli1. This leaves a molecule called c-Rel free to jump in and promote normal T cell proliferation.

This finding could help scientists improve current vaccines. While vaccines are life-saving, some vaccines wear off after a decade or only cover around 80 percent of those vaccinated.
“If you could increase T cell proliferation using a molecule that mimics miR-155, maybe you could boost that to 90 to 95 percent,” said Xiao. He also sees potential for using miR-155 to help in creating longer-lasting vaccines.

The research may also apply to treating autoimmune diseases, which occur when antibodies mistakenly attack the body’s own tissues. Xiao and his colleagues think an mRNA inhibitor could dial back miR-155’s response when T cell proliferation and antibody production is in overdrive.

For the next stage of this research, Xiao plans to collaborate with scientists on the Florida campus of TSRI to test possible miRNA inhibitors against autoimmune disease.
In addition to Xiao, Huang, Liu and Kang, authors of the study, “A miR-155-Peli1-c-Rel pathway controls the generation and function of T follicular helper cells,”  were Cheng-Jang Wu and Li-Fan Lu of the University of California, San Diego; Yi Liu and Alexander Hoffmann of the University of California, Los Angeles; Shunbin Xu of Wayne State University; Guo Fu and Nengming Xiao of Xiamen University; Ye Zheng of The Salk Institute for Biological Studies; and Hyun Yong Jin, Christian J. Maine, Jovan Shepherd, Mohsen Sabouri-Ghomi and Alicia Gonzalez-Martin of TSRI.

Source: http://www.scripps.edu/newsandviews/e_20160815/xiao.html
Madeline McCurry-Schmidt,  News and Views of The Scripps Research Institute

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Manualised protocol of integrated CBT and GET

Posted on 09/22/2016 by wames

Research abstract:

BACKGROUND: Medically-unexplained chronic fatigue states are prevalent, and challenging to manage. Cognitive behavioural therapy (CBT) and graded exercise therapy (GET) are effective in clinical trials. Evaluation of delivery in a standard health care setting is rare. An integrated treatment program with individualised allocation of resources to patients’ needs, was developed and implemented though an academic outpatient clinic. It was hypothesised that the program would result in similar responses to those observed in the clinical trials.

AIM: To evaluate the outcomes of an integrated, 12-week CBT and GET program delivered by exercise physiologists and clinical psychologists.

METHODS: Consecutive eligible patients (n = 264) who met diagnostic criteria for chronic fatigue syndrome (CFS) or post-cancer fatigue (PCF) were evaluated with self-report measures of fatigue, functional capacity, and mood disturbance, at baseline, end-treatment (12-weeks), and follow-up (24-weeks). A semi-structured interview recording the same parameters was conducted pre- and post-treatment by an independent clinician. Primary outcome (fatigue) was analysed by repeated measures ANOVA and predictors of response was analysed by logistic regression

RESULTS: The intervention produced sustained improvements in symptom severity and functional capacity. A substantial minority of patients (35%) gained significant improvement, with male gender and higher pain scores at baseline predicting non-response. A small minority of patients (3%) worsened.

CONCLUSIONS: The manualised protocol of integrated CBT and GET was successfully implemented confirming the generally positive findings of clinical trials. Assessment and treatment protocols are available for dissemination to allow standardised management. The beneficial effects described here provide the basis for ongoing studies to further optimise the intervention and better identify those most likely to respond.

Outcomes and predictors of response from an optimised, multi-disciplinary intervention for chronic fatigue states, by CX Sandler, BA Hamilton, SL Horsfield, BK Bennett, U Vollmer-Conna, C Tzarimas, AR Lloyd in Intern Med J. 2016 Sep 13 [Epub ahead of print]

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PACE trial results were grossly exaggerated

Posted on 09/22/2016 by wames

Occupy ME blog post, by Jennie Spotila, 21 Sep 2016: PACE: Grossly Exaggerated

On September 9, 2016, Queen Mary University of London released data from the PACE trial in compliance with a First Tier Tribunal decision on a Freedom of Information Request by ME patient Alem Matthees. The day before, the PACE authors had released (without fanfare) their own reanalysis of data using their original protocol methods.

Today, Matthees and four colleagues published their analysis of the recovery data obtained from QMUL on Dr. Vincent Racaniello’s Virology Blog.

These two sets of data reanalysis blow the lid off the PACE trial claims.

The bottom line? The PACE trial authors’ claims that CBT and GET are effective treatments for ME/CFS were grossly exaggerated.

Improvers

First, take a look at what the PACE authors’ own reanalysis showed.

When they calculated improvement rates using their original protocol, the rates of improvement dropped dramatically.

pace-per-protocol

As shown in the above graph by Simon McGrath, the Lancet paper claimed that 60% of patients receiving CBT or GET improved. But the reanalysis using the original protocol showed that only 20% of those patients improved, compared to 10% who received neither therapy. In other words, half of the people who benefited from CBT or GET would likely have improved anyway. Remember, the PACE authors made changes to the protocol after they began collecting data in this unblinded trial.

Those changes, used in the Lancet paper, inflated the reported improvement by three-fold.

One would think that the PACE authors would be at least slightly embarrassed by this, but instead they continue to insist:

“All three of these outcomes are very similar to those reported in the main PACE results paper (White et al., 2011); physical functioning and fatigue improved significantly more with CBT and GET when compared to APT [pacing] and SMC [standard medical care].”

Sure, twice as many people improved with CBT and GET compared to standard medical care. But 80% of the trial participants DID NOT IMPROVE. How can a treatment that fails with 80% of the participants be considered a success?

Not only that, but the changes in the protocol were like a magic wand, creating the impression of huge gains in function: 60% improved! The true results, however, are close to a failure of the treatment trial.

Recovery

Today’s publication on Dr. Racaniello’s blog presents the analysis of the recovery outcome data obtained by Alem Matthees. Once again, the mid-stream changes to the study protocol grossly inflated the PACE results.

post-trial-changes

Source: Matthees, et al.

As the graph from the Matthees paper shows, the PACE authors claimed more than 20% of subjects recovered with CBT and GET. Using the original protocol, however, those recovery rates drop by more than three-fold. Furthermore, there is no statistically significant difference between those who received CBT or GET and those who received standard care or pacing instruction. In other words, the differences among the groups could have easily been the result of chance rather than the result of the therapy delivered.

Matthees, et al. conclude, “It is clear from these results that the changes made to the protocol were not minor or insignificant, as they have produced major differences that warrant further consideration.”

In contrast, long time CBT advocate Dr. Simon Wessley told Julie Rehmeyer that his view of the overall reanalysis was, “OK folks, nothing to see here, move along please.”

Taken together, the reanalysis of data on improvement and recovery show that the changes in the protocol resulted in grossly inflated rates of improvement and recovery. Let me state that again, for

clarity: the PACE authors changed their definitions of improvement and recovery and then published the resulting four-fold higher rates of improvement and recovery without ever reporting or acknowledging the results under original protocol, until now. Furthermore, the PACE authors resisted all efforts to obtain the data by outside individuals, spending £250,000 to oppose Matthee’s request alone.

Conclusions

Tuller’s detailed examination of the PACE trial and these new data analyses raise a number of questions about why these changes were made to the protocol:

  • Were the PACE authors influenced by their relationships with insurance companies?
  • Did they make the protocol changes after realizing that the FINE trial had basically failed using its original protocol?
  • Why did they change their methods in the middle of the trial? (Matthees, et al. note that changing study endpoints is rarely acceptable)
  • Were they influenced by the fact that the National Health Service expressed support for their treatments before the trial was even completed?
  • Since data collection was well underway when the changes were made, and because PACE was an unblinded trial, we have to ask if the PACE authors had an idea of the outcome trends when they decided to make the changes?
  • Was their cognitive bias so great that it interfered with decisions about the protocol?
  • Did the PACE authors analyze the data using the original protocol at any point? If so, when? How long did they withhold that analysis?

The grossly exaggerated results of the PACE trial were accepted without question by agencies such as the Centers for Disease Control and institutions such as the Mayo Clinic. The Lancet and other journals persist in justifying their editorial processes that approved publication of these grossly exaggerated results.

The voices of patients have been almost unilaterally ignored and actively dismissed by the PACE authors and by journals. We knew the PACE results were too good to be true. A number of patients worked to uncover the problems and bring them to the attention of scientists.

Their efforts went on for years, and finally gained traction with a broader audience after Tuller and Racaniello put PACE under the microscope.

For five years, the claim that CBT and GET are effective therapies for ME/CFS has been trumpeted in the media and in scientific circles.

Medical education has been based on that claim. Policy decisions at CDC and other agencies have been based on that claim. Popular views of this disease and those who suffer with it have been shaped by that claim.

But this claim evaporates when the PACE authors’ original protocol is used. Eighty percent of trial participants did not improve. Not only that, but we do not have any data on how many people in that group of 80% were harmed or got worse. CBT and GET may not be neutral therapies worth trying in case you fall in that lucky 20% who improved spontaneously or due to the treatment. We don’t know how many people got worse with these therapies, so we cannot assess the risks.

The end result is this: the PACE authors made changes to their protocol after data collection had begun, and published the inflated results. But when the original protocol is applied to the data, CBT and GET did not help the vast majority of participants. The PACE trial is unreliable and should not be used to justify the prescription of CBT and GET for ME patients.

As Matthees, et al., stated in their paper:

“The PACE trial provides a good example of the problems that can occur when investigators are allowed to substantially deviate from the trial protocol without adequate justification or scrutiny. We therefore propose that a thorough, transparent, and independent re-analysis be conducted to provide greater clarity about the PACE trial results.

Pending a comprehensive review or audit of trial data, it seems prudent that the published trial results should be treated as potentially unsound, as well as the medical texts, review articles, and public policies based on those results.”

The reanalysis:

Virology blog: No ‘Recovery’ in PACE Trial, New Analysis Finds, by David Tuller, 21 Sep 2016

More articles:

Stat news: Bad science misled millions with chronic fatigue syndrome. Here’s how we fought back, By Julie Rehmeyer, 21 Sep 2016

ME Action: Patients’ reanalysis sinks PACE’s “recovery” claims 21 Sep 2016

Solve ME/CFS initiative: Preliminary analysis of newly released PACE trial data confirms initial publication results were unsound 21 Sep 2016

Health rising: Data analysis Puts PACE Trial on Slippery Slope to Retraction 22 Sep 2016

Virology blog: Trial By Error, Continued: The Real Data David Tuller 22 Sep 2016

Newsworks blog: Was advice for people with Chronic Fatigue Syndrome all wrong? Julie Rehemeyer 6 Oct 2016

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Patient perceptions regarding possible changes to the name & criteria for CFS & ME

Posted on 09/21/2016 by wames

Research article abstract:

For decades, researchers and patients have been debating the terms and criteria for chronic fatigue syndrome (CFS) and myalgic encephalomyelitis (ME).

This has led to considerable difficulties in clearly communicating to the public the nature of these illnesses, and has produced considerable methodological challenges for researchers who study these illnesses.

If different laboratories do not employ comparable criteria to select patients, this will have negative consequences for understanding epidemiology, etiology, diagnostic and treatment approaches.

In part due to this ongoing controversy, the Institute of Medicine in 2015 recommended new criteria and a new name.

The present study surveyed a relatively large sample of patients both in and outside the US to determine attitudes toward the primary names and criteria that have been used to characterize these patients.

Assessing patient opinions is an activity that might help provide gatekeepers (i.e., federal officials, scientific and patient organizations) with valuable input for ultimately clarifying this debate regarding names and criteria.

Tble 3: Opinion of current names: #CFS, #ME/#CFS, #NDS, #SEID, #ME

Table 4: Opinions of current case definitions.

Patient Perceptions Regarding Possible Changes to the Name and Criteria for Chronic Fatigue Syndrome and Myalgic Encephalomyelitis, by Leonard A. Jason, Laura Nicholson, and Madison Sunnquist in Journal of Family Medicine & Community Health [18 Sep 2016]

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