Friday, 21 September 2018

Open Medicine Foundation Delivers Hope to Millions of Patients

https://www.omf.ngo/2018/09/20/omf-sponsors-second-annual-community-symposium-stanford-university/

For Immediate Release

Sept. 20, 2018 (Los Angeles, CA) – Open Medicine Foundation (OMF), the premier nonprofit organization investing in research to cure myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), sponsors the Second Annual Community Symposium on the Molecular Basis of ME/CFS on September 29, 2018, at Stanford University. This event is expected to draw more than 300 scientists, clinicians, patients, and caregivers as well as over 3,000 attendees globally via livestream.

OMF is working to put an end to ME/CFS – estimated to afflict 20 million globally — by funding a global research effort to identify diagnostic biomarkers, effective treatments, and ultimately a cure. As part of its efforts to foster open, collaborative research, the Foundation is funding a three-day scientific working group meeting in which over 50 world-class scientists with diverse expertise will share their latest results and chart a path forward, followed by the Community Symposium, at which highlights of these results will be shared with the public.

Linda Tannenbaum, OMF founder and CEO/President, will welcome guests at this year’s Symposium and highlight the importance of open collaboration to fast track solutions. The keynote address will be delivered by Oystein Fluge, MD, PhD, of Norway. Additional scientists speaking include the Symposium Chair Ronald Davis, PhD; the Symposium Moderator Raeka Aiyar, PhD; Maureen Hanson, PhD; Jonas Bergquist, MD, PhD; Wenzhong Xiao, PhD; Alain Moreau, PhD; Ronald Tompkins, MD, ScD; Jared Younger, PhD; Michael Sikora, graduate student; and Rob Phair, PhD, who will speak about the new metabolic trap hypothesis.

OMF currently funds ME/CFS Collaborative Research Centers at Stanford and Harvard. Scientists from both Centers will present their research at this year’s symposium.

To register for the Symposium Livestream, click here.

Tuesday, 18 September 2018

Trial By Error: Bruce Levin on “How Not to Conduct a Randomized Clinical Trial”

http://www.virology.ws/2018/09/18/trial-by-error-bruce-levin-on-how-not-to-conduct-a-randomized-clinical-trial/ 

18 September 2018

By David Tuller, DrPH

When I first began examining the PACE trial in detail, I turned to clinical trial experts to vet my concerns. One of them was biostatistician Bruce Levin, a professor at Columbia University’s Mailman School of Public Health, to whom I was referred by a mutual colleague. After he reviewed the trial, he pronounced it to be a mess—a conclusion that fueled my determination to investigate the matter.

Professor Levin identified many faults in the PACE trial’s design and conduct. In particular, he found the overlaps between the entry and outcome thresholds for the key outcomes of physical function and fatigue to be unacceptable peculiarities of the study. “I have never seen a trial design where eligibility requirements for a disease alone would qualify some patients for having had a successful treatment,” said Levin told me for my initial series of articles. “It calls into question the diagnosis of an illness whose patients already rate as ‘recovered’ or ‘within normal range.’ I find it nearly inconceivable that a trial’s data monitoring committee would have approved such a protocol problem if they were aware of it.”

Levin also said the mid-trial publication of a newsletter featuring glowing testimonials from earlier participants and positive news about interventions under investigation created legitimate concerns that subsequent responses might have been biased, especially in an unblinded study with subjective outcomes like PACE. “It is highly inappropriate to publish anything during an ongoing clinical trial,” he told me. “To let participants know that interventions have been selected by a government committee ‘based on the best available evidence’ strikes me as the height of clinical trial amateurism.” (In fact, “the height of clinical trial amateurism” is probably one of my favorite quotes of all time.)

Anyway, last week Professor Levin took his criticism a step further with a public talk about PACE at Columbia. The talk was called, appropriately enough, “How Not to Conduct a Randomized Clinical Trial.” For the last couple of years, I have been pointing out that PACE has been used at Berkeley as a case study of bad science in epidemiology courses. Now it is legitimately possible to say that it has been presented at multiple major American universities as a case study of bad science. Thanks, Bruce!!!

Here is a link to his slide presentation:


Thursday, 13 September 2018

This Man receiveth sinners


C H Spurgeon’s Evening Devotional for 13th September 

"This Man receiveth sinners."

Luke 15:2

Observe the condescension of this fact. This Man, who towers above all other men, holy, harmless, undefiled, and separate from sinners-this Man receiveth sinners. This Man, who is no other than the eternal God, before whom angels veil their faces-this Man receiveth sinners. It needs an angel's tongue to describe such a mighty stoop of love. That any of us should be willing to seek after the lost is nothing wonderful-they are of our own race; but that He, the offended God, against whom the transgression has been committed, should take upon Himself the form of a servant, and bear the sin of many, and should then be willing to receive the vilest of the vile, this is marvellous.

"This Man receiveth sinners"; not, however, that they may remain sinners, but He receives them that He may pardon their sins, justify their persons, cleanse their hearts by His purifying word, preserve their souls by the indwelling of the Holy Ghost, and enable them to serve Him, to show forth His praise, and to have communion with Him. Into His heart's love He receives sinners, takes them from the dunghill, and wears them as jewels in His crown; plucks them as brands from the burning, and preserves them as costly monuments of His mercy. None are so precious in Jesus' sight as the sinners for whom He died. When Jesus receives sinners, He has not some out-of-doors reception place, no casual ward where He charitably entertains them as men do passing beggars, but He opens the golden gates of His royal heart, and receives the sinner right into Himself-yea, He admits the humble penitent into personal union and makes Him a member of His body, of His flesh, and of His bones. There was never such a reception as this! This fact is still most sure this evening, He is still receiving sinners: would to God sinners would receive Him.

Thursday, 6 September 2018

Complaint Report offers hope for those living with ME in Ireland

https://meadvocatesireland.blogspot.com/2018/09/complaint-report-offers-hope-for-those.html?m=1

[This is a long article but well worth reading. I'm posting some of it here; to read the rest, click on the link.]

Christine Fenton

In this post MEAI Advocate Christine Fenton describes her journey with ME and the HSE, elements of which we'll all recognise. The Result? Recommendations for actions by the HSE.

I was diagnosed with Myalgic Encephalomyelitis (ME) in 1990 and retired from my career in teaching, a Deputy Head of a high school in the UK, in 2000. Two years later I moved to Ireland to renovate a derelict house and enjoy my passion for dogs and horses.

In 2003 I deteriorated and was surprised that my then GP was dismissive of the ME diagnosis and regarded it as a mental health issue.

By 2006 I was losing the use of my arms and legs, I'd suddenly find myself sitting on the ground as my legs gave way, often with a horse above me! My arms couldn't manage any repeated use of muscles. I collapsed at an out of hours GP surgery and became paralysed for a short period. The attending GP said she'd never seen anything like this and I should go to Dublin to find the cause.

By chance I had an Out-Patient appointment the week after the collapse and was fortunate to meet with a Consultant new to the local hospital. He was willing to listen and regarded my presentation as an 'interesting challenge'.

My health continued to deteriorate and from 2011-2016 I was spending approx. 3 months annually in acute care.

The difficulties in achieving a home care package to enable me to access the very limited life I was capable of were legion.

Given the limitations of my body, I needed everything available within arms-reach of my resting place. At that time a wooden steamer chair with settee cushions on it was my bed and day chair.

I also needed a consistent temperature as overheating caused me to be unwell very quickly. If my fingers got cold it would trigger severe pain throughout my body, then my legs would give way and I would end up sitting on the floor, sometimes in an unheated room with no ability to return to a warm, comfortable space. I had to resort to pulling ‘something’ from nearby to cover me to increase my core temperature so that I could recover and crawl/push myself, back to safety.

On the days I was too unwell to move, food had to be beside me, small, easy to digest quantities, taken when I had the energy to put food to my mouth, chew, swallow and digest – you’d never believe how hard the action of eating is, something I took for granted when healthy.

At home, as stairs were beyond me and the bathroom was upstairs I had no facilities available to me. Initially I tried a camping cassette toilet, but it was too heavy to empty and needed emptying too frequently. Often it was full on a day I was struggling to use it, never mind empty it. I needed a better solution which met my needs and capability. I decided to use coal buckets as my toilets. When you live in one room and everything, including eating, is done in that room, a steaming commode is just not welcome - we all know the gut problems which accompany ME. There are some indignities I am not willing to contemplate!

The HSE ‘experts on disability’ were nowhere in sight. My request for support at home had been refused without a visit or an assessment being undertaken, no reason was given to explain why I was not worthy of an assessment. Just a refusal letter from an HSE disability manager who made a judgement without any evidence of my needs on which to base it.

So, I was on my own and had no choice but to create a system which allowed my needs to be met, within the resources available to me.

To continue reading the article, click on –

Saturday, 1 September 2018

Letter to Professor Watt of MRC



This letter from Professor Fiona Watt of the Medical Research Council in support of the PACE Trial appeared a few days ago in response to the Times article about the growing pressure on The Lancet concerning the trial:

CHRONIC FATIGUE

Sir, Further to your report “Call for review of ‘flawed’ ME research”(Aug 21), as funders of the Pace trial we reject the view that the scientific evidence provided by the trial for using cognitive behavioural theory and managed exercise in the treatment of chronic fatigue syndrome (also known as ME) was unsound. The Pace trial was funded following expert peer review, was overseen by an independent steering committee, and its published findings have also been independently peer-reviewed. Other research groups have drawn similar conclusions. Chronic fatigue syndrome/ME remains a priority for the Medical Research Council (MRC), and it is important that researchers are not discouraged from working on the disease because of concerns that they could be subject to the level of hostility that Pace researchers have experienced. Medical research can only flourish when there is mutual respect between all parties.

Professor Fiona Watt Executive chairwoman, Medical Research Council

There have been other responses from patients. Here is mine, which I decided to send directly to Prof Watt.

Maybe she will see it. Maybe she will read it. Maybe she will do as I ask! I’ve sent it anyhow. You don’t win the lottery if you don’t buy a ticket…

Dear Professor Watt,

Like many patients with M.E. I was surprised and disappointed by your letter to The Times wholeheartedly supporting the PACE trial. There are so many misconceptions in the letter that it is clear that you have not investigated this matter yourself but have – apparently- assumed that what the PACE authors tell you about it is correct and what patients tell you is not. I can only assume that this is because they are doctors and we are merely patients.

Yet you say in your letter that ‘medical research can only flourish when there is mutual respect between all parties’. I would certainly not disagree with that. Please then show patients the respect of being open to the possibility that what we (and indeed many distinguished researchers and other informed parties) say about PACE may actually be correct.

I am not asking you to take us at our word, but please look into the matter yourself instead of simply believing what you are told by the PACE authors and their friends. It will not take you long. I have provided a few references at the end of this letter which you will find useful. For the sake of the patients you say you wish to respect, please take the trouble to do this.

Thank you,

Useful references:

Rethinking the Treatment of Chronic Fatigue Syndrome – A Reanalysis and Evaluation of Findings from a Recent Major Trial of Graded Exercise and CBT by Wilshire et al. – Jan 2018 (A comprehensive re-evaluation of PACE following the release of data from the Freedom of Information Act Tribunal.)

Journal of Health Psychology Vol 22 No.9 Aug 2017 – A Special Issue on PACE. “On the basis of this Special Issue, readers can make up their own minds about the merits and demerits of the PACE Trial,” writes Editor David F Marks.

A letter to The Lancet signed by over a hundred scientists, clinicians, academics, MPs and other experts plus over sixty local, national, and international patient organisations, calling for an independent re-analysis of PACE and setting out the reasons why.

The August 2016 PACE Trial Freedom of Information Tribunal Judgement has useful information about so called hostility to PACE researchers, an unfounded allegation which your letter unfortunately perpetuates.

Two notes relating to this issue:

Allegations were made at the Tribunal by a representative of the PACE proponents that ME patients, described as ‘activists’ were ‘borderline sociopathic and psychopathic’ and posed ‘a serious threat of violence to trial participants and researchers’ but the Commissioner described these as ‘wild speculations’ which did the representative ‘no credit’ (see pages 22 and 36). PACE researcher Prof Chalder accepted that ‘there had been no threats made either to researchers or participants’ The Commissioner stated that the ‘assessment of activist behaviour was grossly exaggerated. The only actual evidence was that an individual at a seminar had heckled Prof Chalder.’ (see page 40)
Your letter also suggests that researchers might be ‘discouraged from working on the disease because of concerns that they could be subject to the level of hostility that PACE researchers have experienced’. The idea that researchers are being discouraged in this way is another often repeated misconception which seems to be intended to vilify patients. Working for the MRC, you will be fully aware of how little funding M.E. has received over the years. Nevertheless there is research going on worldwide, strongly supported by patients and often funded by them. (Many of these researchers are critical of PACE and have signed the letter to The Lancet requesting its independent reassessment – see above.) Patients do however object – in the form of letters such as this and other peaceful means – to the squandering of funds on poorly conducted research such as PACE, money which is desperately needed for high quality biomedical research into the condition.

Tuesday, 21 August 2018

The Times: Call for review of ‘flawed’ ME research in Lancet letter

https://www.meassociation.org.uk/2018/08/the-times-call-for-review-of-flawed-me-research-in-lancet-letter-21-august-2018/

On the ME Association website – 

Tom Whipple, Science Editor, The Times, August 21, 2018.

More than a hundred academics have joined ten MPs and scores of patient groups from around the world to sign an open letter calling for The Lancet to reanalyse a study into treatment for myalgic encephalomyelitis (ME).

The letter follows a debate in parliament in which one MP said that the study, which is used to set NHS guidelines, “will go down as one of the biggest medical scandals of the 21st century”.

The authors of the research paper stood by their findings and said that the letter represented a campaign to discredit solid research and force the retraction of papers simply because patients disagreed with their findings.

The signatories, who include academics from Harvard, Stanford, UCL and the London School of Hygiene and Tropical Medicine, said that the 2011 Pace trial, which recommended therapy and exercise as a treatment for the condition, had “major flaws” and “unacceptable methodological lapses”.

The £5 million publicly funded trial was published in The Lancet and has informed advice on treating people with ME in the NHS and abroad, but is controversial among ME sufferers. Some claim that its advice perpetuates an idea that the disease, which causes debilitating disability, is all in the mind.

The Lancet declined to comment.

--------------------------

Virology Blog:

Trial By Error: Open Letter to The Lancet, version 3.0

David Tuller, 13 August 2018

Two months ago, Professor Racaniello sent Lancet editor Richard Horton an open letter about the indisputable methodological and ethical failings of the PACE trial. This was a follow-up to Virology Blog’s 2016 open letter to Dr. Horton; the new one detailed what has happened since then. Last month, I re-sent and reposted this new open letter, with organizations also signed on. Given Dr Horton’s persistent defense of a study in which 13 % of the participants had already met a key outcome threshold at baseline, it is not surprising that he has failed to respond.

Yesterday I sent the letter to The Lancet for the third time, with more individual experts and organizations adding their voices to the demand for a reassessment of the reported PACE findings. For reasons only Dr Horton can explain, he appears determined to undermine his journal’s reputation for scientific integrity with his robust support for a trial that objective observers clearly recognize as a piece of crap. PACE has caused great harm to the patient community. Dr Horton’s refusal to take appropriate corrective action has amplified that harm many times over. He and his journal have a lot to answer for.

Dear Dr. Horton:

In February, 2011, The Lancet published an article called “Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomized trial.” [1] The article reported that two rehabilitative approaches, cognitive behavioural therapy (CBT) and graded exercise therapy (GET), were effective and safe treatments for chronic fatigue syndrome, also often referred to as myalgic encephalomyelitis, ME/CFS and CFS/ME. The PACE study received international attention and has had widespread influence on research, treatments prescribed for patients, and attitudes toward the illness of both the medical community and the public at large.

At the press conference promoting the Lancet paper, one of the lead investigators stated that twice as many participants in the treatment groups got “back to normal,” compared to those in the other study arms. [2] An accompanying Lancet commentary similarly claimed that these “back-to-normal” participants had met a “strict criterion for recovery.” [3]

In fact, we now know that 13 % of the participants qualified at baseline as “recovered” or “within the normal range” for one of the study’s two primary measures, self-reported physical function–even as they were simultaneously classified as disabled enough on the same measure to enter the study. [4] This anomaly, which occurred because the investigators weakened key outcome thresholds after data collection, invalidates any claims that patients “recovered” or got “back to normal.” The overlap in entry and outcome criteria is only one of the trial’s unacceptable methodological lapses.

The treatments investigated in the PACE trial were based on the hypothesis that ME/CFS patients harbor “unhelpful” convictions about having an ongoing organic disease and that the perpetuation of their devastating symptoms is the result of deconditioning. In contrast, a 2015 review from the U.S. Institute of Medicine (now the National Academy of Medicine), reported that ME/CFS is a complex, multi-system illness characterized by neurological, immunological, autonomic, and energy metabolism dysfunctions. [5] The cardinal symptom, noted the review, is a systemic intolerance to exertion; if patients exceed their available energy resources, they can suffer serious and prolonged relapses.

After The Lancet published the first PACE results, ME/CFS patients and advocates immediately pointed out major flaws. But few people outside the field took notice until the science site Virology Blog published a 15,000-word investigation by David Tuller, a public health researcher and journalist at the University of California, Berkeley, in October of 2015. [6] Subsequently, in February of 2016, many of us signed an open letter to The Lancet requesting an independent investigation of the study. [7]

Since then, much has happened:

* In August of 2016, a U.K. tribunal, citing that open letter, ordered Queen Mary University of London to release raw trial data from the PACE study, sought by Australian patient Alem Matthees in a freedom of information request so that he and others could calculate the outcomes promised in the PACE trial protocol. [8]

* Analyses of these data [9], including a study published in BMC Psychology in March [10], have confirmed what has long been argued: The PACE investigators engaged in such extensive outcome-switching that they were able to report dramatically better findings than the null or minimal results obtained under the original measures they promised in their protocol.

* The U.S. Agency for Healthcare Research and Quality (AHRQ) downgraded its recommendations for CBT and GET. [11] This downgrading occurred after the agency removed from its analysis the PACE trial and other studies using overly broad selection criteria that generated cohorts of patients with a grab-bag of fatiguing conditions. And while the PACE trial claimed that GET is safe, AHRQ found that the therapy was associated with more adverse events.

* Last summer, the U.S. Centers for Disease Control abandoned the recommendations that ME/CFS patients be treated with CBT and GET [12], having already removed references to the PACE trial. A couple of months later, the U.K. National Institute for Health and Care Excellence announced that it would pursue a full update of its 2007 guidance, citing concerns about the reliability and validity of the evidence base. [13]

* Earlier this year, a report from the Dutch Health Council recommended that GET should not be used in the Netherlands as a treatment for the illness. [14]

* In March, a group of leading American clinicians who specialize in ME/CFS unanimously agreed that the two PACE treatments are inappropriate and possibly harmful for patients with the illness and should therefore not be prescribed. [15]

Given the worldwide impact of PACE, we urge The Lancet to do what the open letter two years ago requested: commission an independent re-analysis of the individual-level trial data, with appropriate sensitivity analyses, from highly respected reviewers with extensive expertise in statistics and study design. The reviewers should be from outside the domains of psychiatry and psychological medicine and predominantly from outside the U.K. They should also be completely independent of, and have no conflicts of interests involving, the PACE investigators and the funders of the trial.

Thank you for your quick attention to this matter.

Sincerely,

For the full list of signatories please refer to virology blog. Dr Charles Shepherd and Dr Nigel Speight, medical advisers to the ME Association, together with the Countess of Mar, representing Forward ME, also signed the letter.

The UK Members of Parliament who signed were as follows:

Sir Edward Davey MP
Kingston and Surbiton, England, UK

David Drew MP
Stroud, England, UK

Patricia Gibson MP
North Ayrshire and Arran, Scotland, UK

Mary Glindon MP
North Tyneside, England, UK

Sandy Martin MP
Ipswich, England, UK

Carol Monaghan MP
Glasgow North West, Scotland, UK

Nicky Morgan MP
Loughborough, England, UK

Alex Sobel MP
Leeds North West, England, UK

Graham Stringer MP
Blackley and Broughton, England, UK

Stephen Timms MP
East Ham, England, UK

Friday, 17 August 2018

This Sickness Is Not Unto Death

http://bible.christiansunite.com/Morning_and_Evening/chme0817.shtml

C H Spurgeon’s Evening Devotional for 17th August

“This sickness is not unto death”

John 11:4

From our Lord's words we learn that there is a limit to sickness. Here is an "unto" within which its ultimate end is restrained, and beyond which it cannot go. Lazarus might pass through death, but death was not to be the ultimatum of his sickness. In all sickness, the Lord saith to the waves of pain, "Hitherto shall ye go, but no further." His fixed purpose is not the destruction, but the instruction of His people. Wisdom hangs up the thermometer at the furnace mouth, and regulates the heat.

1. The limit is encouragingly comprehensive. The God of providence has limited the time, manner, intensity, repetition, and effects of all our sicknesses; each throb is decreed, each sleepless hour predestinated, each relapse ordained, each depression of spirit foreknown, and each sanctifying result eternally purposed. Nothing great or small escapes the ordaining hand of Him who numbers the hairs of our head.

2. This limit is wisely adjusted to our strength, to the end designed, and to the grace apportioned. Affliction comes not at haphazard-the weight of every stroke of the rod is accurately measured. He who made no mistakes in balancing the clouds and meting out the heavens, commits no errors in measuring out the ingredients which compose the medicine of souls. We cannot suffer too much nor be relieved too late.

3. The limit is tenderly appointed. The knife of the heavenly Surgeon never cuts deeper than is absolutely necessary. "He doth not afflict willingly, nor grieve the children of men." A mother's heart cries, "Spare my child"; but no mother is more compassionate than our gracious God. When we consider how hard-mouthed we are, it is a wonder that we are not driven with a sharper bit. The thought is full of consolation, that He who has fixed the bounds of our habitation, has also fixed the bounds of our tribulation.