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Get a Ringside Seat for Invest in ME’s 10th International Conference on 29 May

Sasha and Simon preview the attractions and tells you how you can watch it unfold …

This Friday, 29 May sees the tenth International ME Conference put on by UK research charity Invest in ME (IiME) in London. The day-long conference will include 220 participants from 17 countries and will be attended by researchers, clinicians and patients.​

london-by-night-735085_1280The conference has grown from small beginnings to being one of the most important events on the international ME research calendar, not least because it’s preceded by a two-day, invitation-only research colloquium — now in its fifth year — where some of the world’s top ME researchers can put their minds together and make things happen.

IiME used their 2013 colloquium to gather researchers who might be interested in a UK replication of the exciting rituximab trial results seen in Norway and their initiative paid off.

A University College London team, led by Jo Cambridge and advised by Emeritus Professor Jonathan Edwards, took up the challenge to do a UK trial and IiME began a wildly successful, ongoing crowdfund for the research which has raised a spectacular £380,000 ($590,000, €530,000) so far.

So, we can expect big things. The colloquium happens behind closed doors but the conference doesn’t, and Mark Berry from Phoenix Rising will be in the audience, preparing an in-depth article about the research (his 2013 coverage is here, and 2014 here and here). He and others will be tweeting for Phoenix Rising so that you can follow the presentations live.

Professor Olav Mella (left) and Dr Oystein Fluge

Professor Olav Mella (left) and Dr. Oystein Fluge

The stars of the show are likely to be Oystein Fluge and Olav Mella with the latest from Norway on the new, multi-centre rituximab trial, with Jo Cambridge reporting on B-cell profiling aimed at identifying likely responders in the forthcoming IiME UK rituximab trial.

Other highlights include John Chia on how enteroviruses might cause ME/CFS, Mady Hornig on markers of immunity and metabolism, Betsy Keller on molecular markers before and after exercise and Louis Nacul on ME/CFS population rates.

There’s also brain-immune communication, proteomics explained, an update from Down Under by Sonya Marshall-Gradisnik, and Amolak Bansal on better diagnosis. Professor Ian Charles will deliver the keynote address, on what a research park can do to solve a chronic illness.

The full programme is as follows:

08.55    Dr. Ian Gibson   Conference Opens
09.05    Professor Ian Charles   (Keynote Speech) Solving ME: What a Research Park Has to Offer in Resolving a Chronic Disease
09.30    Professor Mady Hornig   Markers of Immunity and Metabolism in ME/CFS
10.00    Professor Jonas Bergquist   Proteomics in ME/CFS
10.25     Refreshments Break
10.50    Dr. Luis Nacul   Incidence and Prevalence of ME
11.15     Dr. Amolak Bansal   Diagnosis and Differential Diagnosis: Combining clinic and research
11.45     Professor Sonya Marshall-Gradisnik, Dr Don Staines   (To be confirmed) Update from National Centre for Neuroimmunology and Emerging Diseases – NCNED
12.15      IiME Projects    Student Researchers: The Next Generation
12.40     Lunch
13.40     Dr. Jo Cambridge  B-cell biology and ME/CFS
14.05     Dr. Neil Harrison   Immune-Brain Communication and Relationship to Inflammation
14.30     Dr. John Chia   ME and Chronic Enterovirus Infection: An Update on pathogenesis.
14.55     Dr. Claire Hutchinson   Biomarkers for ME: Visual Processing and ME/CFS
15.20     Refreshments break
15.50     Professor Betsy Keller   Molecular markers before/after exercise /Activity guidelines to avoid symptom flares
16.15      Dr. Oystein Fluge, Professor Olav Mella   Multi-centre Rituximab Clinical Trial for ME/CFS
17.10     Plenary   Will ME Be Treatable/Cured?
17.30     Dr. Ian Gibson   Adjourn

Until 31 May you can get an ‘early bird’ price on Invest in ME’s DVD of the conference, which will be released in July.

And, of course, feel free to donate to IiME’s research! They have a general biomedical research fund, a rituximab trial fund, and a fund for a study on the gut, looking at the microbiome and gut-wall permeability (‘leaky gut’).

This is a small charity that punches well above its weight and is well worth supporting.

So, we’ve got something to look forward to on Friday — and don’t forget to tune in for Phoenix Rising’s live tweeting from the ringside.

Let’s hope for a conference to remember!
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{ 210 comments… add one }

  • Sushi May 30, 2015, 8:26 pm
    Mark

    But the importance of identifying what ME/CFS patients can do without inducing PEM is huge, if you think about it, and her practical strategies for establishing and maintaining Core Stability

    This is something I have worked with a lot on a personal level. I used to teach yoga but found that the standing, arms-over-the-head and the aerobic nature of some of the poses was no longer possible for me. So I tried pilates with machines, focusing on core strength and done mostly lying down. I have been doing this for about 6 years and, while it doesn't help "ME/CFS" it does keep muscles in decent shape and helps hugely with the aches and pains of EDS.

    Mark

    A YouTube 'exercise video' on this would be a fantastic resource. It's going to be tricky for me to describe it all adequately in words…:eek:

    A YouTube would be excellent. Is their some way that Phoenix Rising could promote that idea to Betsy Keller?

    Sasha

    I find any general advice to do yoga or similar things deeply, deeply unhelpful because there's a shedload of yoga moves. Just saying 'do some yoga' is not help at all, especially for patients who have OI issues (most of us) – there's a lot of 'arms above heart' stuff that will do us in.

    Exactly, that is why, for me, pilates lying down is a whole different experience.

    SOC

    Also, patients with ill-controlled OI probably can't do standing or even upright sitting exercise like yoga and Tai Chi.

    MEMum

    Her pictures and exercises reminded me more of Pilates, than yoga, in my limited experience.

    MEMum

    I have found a Pilates class where we do most exercises lying down and I feel that my daughter could do some of the stretches, for a few minutes at a time.

    Pacing is my challenge even though we are lying down. I use an HR monitor and the instructor is fine with me doing just what I can.

    Having said all that, I am a moderate patient not severe. Yet some of the core exercises could, I think, be modified for severe patients, given plenty of rest and recovery between each "rep." I know that some are too severe for any type of exercise, even stretching, but for others there could be advantages to pilates done with machines (which use weight (springs actually) to assist you. The downside is that the machines are very expensive so the classes can be a bit pricey.

    Sushi

  • eafw May 30, 2015, 9:04 pm
    Sushi

    pilates lying down is a whole different experience.

    The only "exercise" I ever found useful was passive movement, while lying down and with another person taking all the weight and moving my limbs and joints for me. It did help slow the decline, but is almost impossible to find someone who understands how to do this, especially in the context of ME.

    Would be interested to see Dr Keller's stuff, if she deals with this very basic sort of movement.

  • daisybell May 30, 2015, 9:35 pm

    Dr Keller was suggesting that any exercise/activity must not be aerobic, as this form of energy production is broken in us. So the strengthening and stretching exercises should be done in very short bursts, with at least twice the amount of rest following each bit of activity. She also suggested that if necessary, these should all be done lying down. At no point should anyone with ME get too out of breath to be able to talk easily…. And basically our activity should be mostly one level up from doing nothing!

  • Scarecrow May 30, 2015, 9:44 pm
    SOC

    And the fact that while mild patients may be able to do yoga or Tai Chi, many moderate to severe patients have tried it and had PEM from it. Also, patients with ill-controlled OI probably can't do standing or even upright sitting exercise like yoga and Tai Chi.

    Both the experts and patients need to remember that the patients the ME/CFS exercise experts see are mostly mild patients, so their casual exercise recommendations probably apply to those patients, not all patients.

    First of all, my Daily Mail comment in response to Mark was a bit flippant. I didn't mean to offend and I apologise.

    I have to disagree about Betsy Keller only mostly seeing mild patients, though. As a mild patient, I can't think what I would gain from consulting an exercise physiologist. Mild patients should be active enough not to need to. Betsy Keller sees a lot of patients who need help with disability claims – see Cort's blog. Those are not mild patients (nor severe, obviously).

    About four months ago, within the space of only a few days, I went from being able to walk at a reasonable pace for a couple of miles, without any ill effects, to having to do the washing up in several stages. A short walk completely incapacitated me for hours. Fortunately, I'm getting back to my pre crash level but in the relatively short period of time that my activity has been restricted, I can see that a degree of deconditioning is starting to kick in. Note that I am clearly saying that the deconditioning is a result of the crash and not the other way round. If I'd had the foresight, I probably would have done some stretching and light strengthening exercises to maintain a little bit of flexibility and keep the lymph moving. As it is, it's no big deal because it's only been a matter of months.

    We are not designed to be inactive. There are consequences of inactivity for everyone just as there are consequences of too much activity for PWME. Mild patients should only have to concern themselves not to exceed their limits but as severity increases it becomes ever more impossible to balance the equation. Perhaps that is where exercise physiologists can help.

    We've focussed too much on the Tai Chi / yoga element in Betsy Keller's presentation. My fault, everyone. Sorry!

    It's worth quoting again what Kina tweeted. I think it's clear that (1) Keller 'gets' ME (2) her advice is tailored to the individual and that (3) she is aiming squarely at moderate patients at the lower end and severe patients at the upper end, depending on interpretation of moderate and severe.

    mango

    Tweets by Kina/Phoenix Rising https://twitter.com/aboutmecfs
    Prof Betsy Keller

    There are activity guidelines that should be paid attention to.

    Will talk about energy currency — short-term anaerobic (immediate stores available on demand), long term anaerobic and aerobic.

    Our aerobic energy system has gone awry in ME/CFS.

    PEM is a defining quality of ME. ME is not JUST fatigue.

    Bateman — pre-emptive rest on a schedule, pace yourself.

    As a patient you need to redefine and focus on what works for you.

    Goal — improve range of motion, improve functional strength, and improve core stability.

    Core stability is musculature that supports your spine.

    With poor core stability — you overuse your extremities.

    Spinal alignment is key for good function and energy conservation.

    Going through how to align the spine properly. Warm-up always begins with nose-breathing (thru the nose, 4 sec in, 6-8 sec out)

    Relaxing, relieves pain. Has to become a havit.

    There are 5 simple steps to align the spine. 1. Contract pelvic floor. eg for women — eg kegel exercises

    2. Draw-in or Brace ('suck belly-button into spine.) to stabilize pelvis 3, Raise ribcage – pretend ribcage is an umbrella

    4. Back extension — lie on floor in flying Superman pose – slide shoulder blades together or shoulders back and down. 5. Retract chin is the last step to aligning spine.

    Giving examples of gentle exercises to strengthen to core — eg physio ball, start with a chair first, yoga etc.

    Physical activity progression — start with stretching and core stability. Stage 2 = stretching with resistance activity

    Stage 3 = Dose controlled Interval Activity Stage 4 = Maintenance Goal = improved function. These stages can take as much time as needed.

    When structured physical activity does work, you can increase activity eg 10 seconds with 30 seconds rest —

    Activity biofeedback is good — monitor heartrate with a HR monitor. With ME, exceeding a certain HR will cause issues.

    Can use a 'Perceive Exertion scale' to monitor responses/tolerance to activity.

    Energy conservation is a MUST.

    Discussing energy saving tips — eg shower chair, pack groceries in a smart way, cook ahead, monitor calls, disabled parking placard,

    learn to say no to 'energy zappers'.

  • hopeful2 May 30, 2015, 10:00 pm

    I would love to see what Prof. Betsy Keller had to say for my self. If I purchase the DVD will her complete talk be on there?

    I would love to see her put all of her recommendations for movement in a video that people could follow at home. Then each one of us could experiment for ourselves to see what we can tolerate and what we can't but it would at least be a starting point.

  • Sushi May 30, 2015, 10:50 pm

    I found a YouTube (sorry about the commercial at the beginning) that shows a way to exercise the legs lying down on the pilates reformer machine. The teacher in the video has attached all the springs to make it as hard as possible. There are 5 springs of varying tensions and you can attach just one light one if you wish. This video just gives a visual to my post above.

  • alex3619 May 30, 2015, 11:02 pm
    Mark

    No idea, but it would be good if somebody would. Along with the visual processing findings, I'd love to see this documented in a decent sized cohort. Maybe the thing to do would be to investigate the correlation of these signals with other objective signs and with various diagnostic criteria, to try to get a handle on subgrouping, but I'm not quite sure how that might work…

    This is the kind of thing that has the potential to be rapidly moved to clinical practice. Sadly I first heard of this kind of thing in 1993. Its taken 22 years, but finally a formal study.

  • alex3619 May 30, 2015, 11:03 pm
    Sean

    I am disappointed at all these results, people. We clearly didn't manage to scare away enough good researchers.

    :p

    We have to work harder or we wont get that Babble Gold Star! :star:

  • Denise May 30, 2015, 11:28 pm
    Kina

    It wasn't Mark tweeting. It was me. It's a real eye opener and very exciting for me to be able to attend IiME. You can do whatever you want with my tweets except call me an idiot because I got things wrong or misinterpreted something. It's all very hard on me, I am exhausted. Time to crash. Mark was taking extensive notes for his article.

    Please know that your energy expenditure is much appreciated!
    I am very glad you were able to attend! :)

    I look forward to Mark's article.

  • rosie26 May 31, 2015, 7:33 am

    I feel so much relief that research is looking so much better for us. Can't thank these researchers enough for their determination and focus. It is all very encouraging. Thanks to all who reported from the conference, it was great. I think we all would have loved to have been there and to have heard the embargoed things – will have to have patience.

  • Kate_UK May 31, 2015, 2:38 pm

    Thank you for the conference reports. Invest in ME are great.

  • Valerie Eliot Smith June 4, 2015, 6:08 pm

    This isn't going to help anyone with the science but I'm posting it because of my acknowledgment to PR for the tweets from the conference. The rest is mostly my personal observations from the day plus some links which aren't new but might be of use to some http://valerieeliotsmith.com/2015/06/04/science-versus-history-a-snapshot-of-invest-in-mes-10th-annual-conference/

  • JaimeS June 6, 2015, 6:04 am

    I want to order the DVD, but my bank won't let me order overseas without Special Permission…

    Last time I tried to get it, they accidentally cancelled the card. :bang-head:

    -J

  • lansbergen June 6, 2015, 9:11 am
    JaimeS

    I want to order the DVD, but my bank won't let me order overseas without Special Permission…

    Last time I tried to get it, they accidentally cancelled the card. :bang-head:

    -J

    Can't you use paypall?

  • Sasha June 24, 2015, 9:52 am

    IiME have now posted on their website a conference summary by Dr Ros Vallings:

    http://www.investinme.eu/IIMEC10.shtml#report

  • aimossy June 24, 2015, 11:41 am

    Thanks @Sasha

  • Sasha August 1, 2015, 11:51 am

    Just received an email update:

    IiME

    Dear Friends,

    Invest in ME are pleased to announce that the IIMEC10 conference DVD is
    now having its final proof-checking performed.
    This means that the production version will be encoded and produced this
    next week.

    Following this we will begin delivery.
    We hope you enjoy the DVD as a great deal of effort and resource has
    gone into its production.
    We thank you for your continued support,

    Best wishes
    Invest in ME

  • Battery Muncher August 1, 2015, 6:30 pm

    Great news.

    I wonder if a downloadable version will be available that we could download straight off the website?

  • Bob August 1, 2015, 6:38 pm
    Battery Muncher

    I wonder if a downloadable version will be available that we could download straight off the website?

    No, it won't be available as a download or streaming. Invest in ME never provide a web version of their videos. I'm not sure why. Placing all of their conferences for sale on Vimeo might bring in some extra income.

  • Sasha August 1, 2015, 6:47 pm
    Bob

    No, it won't be available as a download or streaming. Invest in ME never provide a web version of their videos. I'm not sure why. Placing all of their conferences for sale on Vimeo might bring in some extra income.

    That's a great idea – perhaps someone would email them and suggest it. Very win-win, I'd have thought.

  • Sasha August 5, 2015, 10:36 am
    IiME on FB

    Conference DVD for IIMEC10 is now completed (some last minute embargoed information had to be verified by a presenter) and is in the process of being produced ready for distribution as soon as they are ready and packed.

    Really looking forward to getting my DVD!

  • RL_sparky August 5, 2015, 4:47 pm
    Sasha

    Really looking forward to getting my DVD!

    So am I. I was just reading over Mark's excellent notes again about the conference. The only bummer with these DVDs will be the embargoed information that will be missing. Kind of like watching a movie and they cut the best parts out!
    Excerpt:

    Professor Mady Hornig:“2015 seems to be the year, in which we’re seeing so much coming together, and so much synergy, across the globe really”

    They’re planning a new follow-up microbiome study in association with the Chronic Fatigue Initiative (CFI).

    Specifically, noted eotaxin: 33 times the level of controls in the patients they studied.

    The embargoed content was the results of the metabolomics study, as Simon guessed. They’re still going through and analysing the results and trying to figure out what it all means. The one snippet she did let go looks to me like another important piece of the puzzle…but I’m not going to break the embargo on that…

    Professor Jonas Bergquist:
    The embargoed info in this presentation concerns a fairly small study which hasn’t been published yet, but again looks to me like a significant piece of the puzzle.

  • Research 1st August 5, 2015, 6:27 pm
    RL_sparky

    So am I. I was just reading over Mark's excellent notes again about the conference. The only bummer with these DVDs will be the embargoed information that will be missing. Kind of like watching a movie and they cut the best parts out!
    Excerpt:

    Specifically, noted eotaxin: 33 times the level of controls in the patients they studied.
    .

    Thanks for the update.

    That's interesting to know as this paper from the WPI showed increased Eotaxin levels in CFS patients with inflammation, including glial activation markers.

    The majority of up-regulated factors were members of the CXC or CC chemokine family. The greatest statistical difference was seen in chemotactic factor IL-8, a major mediator of the inflammatory response, with a mean value of 1045±245 pg/mL in patients compared to a mean of only 13.1±1.6 pg/mL as seen for the healthy controls. The other up-regulated chemokines, also from the CXC or CC family, were MIP-1β, MIP-1α, IP-10, eotaxin, MCP-1 and RANTES; two members of the cytokine family, IL-2 and TNF-α, were also up-regulated.

    Full PDF Link:
    http://iv.iiarjournals.org/content/25/3/307.full.pdf html

    It would nice to have a test for Eotaxin, and to see if forum members can replicate this approx 33 times increase, you mentioned. I wonder if there is a test commercially?

  • RL_sparky August 5, 2015, 7:55 pm
    Research 1st

    I wonder if there is a test commercially?

    I just did a brief search online and do not see a commercially available test. I'm sure will see one available if more patients exhibit these levels. I wonder if this is elevated in other disease groups?

  • Kyla August 5, 2015, 8:07 pm
    RL_sparky

    I just did a brief search online and do not see a commercially available test. I'm sure will see one available if more patients exhibit these levels. I wonder if this is elevated in other disease groups?

    I think the Eotaxin findings were in Spinal fluid, so this would not likely be available commercially.

  • Sasha August 5, 2015, 8:17 pm
    RL_sparky

    Specifically, noted eotaxin: 33 times the level of controls in the patients they studied.

    I don't really get what this eotaxin stuff is.

    Wikipedia

    The eotaxins are a CC chemokine subfamily of eosinophil chemotactic proteins.

    o_O

    But @Jonathan Edwards – does this fit in with the autoimmune theory?

  • RL_sparky August 5, 2015, 8:20 pm
    Kyla

    I think the Eotaxin findings were in Spinal fluid, so this would not likely be available commercially.

    I didn't know that..Thanks

  • halcyon August 5, 2015, 9:02 pm

    Commercial assays clearly exist for eotaxin and other chemokines, but consumer labs like LabCorp and Quest don't seem to offer more than a handful of interleukin assays at this time.

  • Scarecrow August 5, 2015, 9:04 pm

    There was a discussion about eotaxin earlier in the thread for a couple of pages. There's also a link to another thread contained in the first post.

  • Kyla August 5, 2015, 9:07 pm
    halcyon

    Commercial assays clearly exist for eotaxin and other chemokines, but consumer labs like LabCorp and Quest don't seem to offer more than a handful of interleukin assays at this time.

    My point was that if the findings are specifically for spinal fluid a blood test for Eotaxin probably isn't going to show you anything.
    https://www.mailman.columbia.edu/pu…ognitive-dysfunction-chronic-fatigue-syndrome
    Unless someone else has found the same results in blood?

  • halcyon August 5, 2015, 9:12 pm
    Kyla

    My point was that if the findings are specifically for spinal fluid a blood test for Eotaxin probably isn't going to show you anything.
    https://www.mailman.columbia.edu/pu…ognitive-dysfunction-chronic-fatigue-syndrome
    Unless someone else has found the same results in blood?

    I was directing that more towards @RL_sparky. You're correct, the CCL11 findings were only in the CSF study.

  • Scarecrow August 5, 2015, 9:12 pm
    Scarecrow

    There was a discussion about eotaxin earlier in the thread for a couple of pages. There's also a link to another thread contained in the first post.

    It seems like CCL11 was the form measured in the published study but it wasn't 33 times higher in patients. I wonder if the 33x figure relates to another form, the one Mark mentioned as being associated with endothelial cells.

  • Jonathan Edwards August 6, 2015, 7:34 am
    Sasha

    I don't really get what this eotaxin stuff is.

    o_O

    But @Jonathan Edwards – does this fit in with the autoimmune theory?

    These cytokines often get identified by one thing they do and then gradually we come to see that they do lots of other things. Autoimmunity can trip up any mechanism you like. If the business end of an antibody molecule mimics or binds to any one of 40,000 proteins it can modulate the action that protein. There are about 10,000,000,000,000,000… possible antibody business ends (the number is almost infinite).

  • Sasha August 6, 2015, 8:24 am
    Jonathan Edwards

    These cytokines often get identified by one thing they do and then gradually we come to see that they do lots of other things. Autoimmunity can trip up any mechanism you like. If the business end of an antibody molecule mimics or binds to any one of 40,000 proteins it can modulate the action that protein. There are about 10,000,000,000,000,000… possible antibody business ends (the number is almost infinite).

    So it's fair to say it could be consistent with the autoimmune theory but has so many possible functions that it's not evidence that points in one direction rather than another?

  • Avengers26 August 9, 2015, 2:19 am

    I just read this thread. I want to thank @Kina , @Sasha , @mango , @Mark & others for the time & effort they put in getting us these updates.

  • Sasha August 11, 2015, 11:14 am

    It's in the mail!

    IiME by email

    Dear Friends

    We have now dispatched your order for the 10th Invest in ME
    International ME Conference DVD.

    Our apologies for the delay in anticipated delivery but we had some
    last-minute work to remove additional unpublished data from one of the
    presentations.

    Thank you for ordering the DVD and we hope to benefit from it.

    Please feel free to give feedback as this helps us for the future,

    Best wishes
    Invest in ME

  • Sasha August 12, 2015, 1:21 pm

    Just got my DVD in the mail! :woot:

    Here's the order page, for anyone who hasn't ordered theirs yet.

  • Bob August 13, 2015, 12:11 pm

    Received my copy this morning! :) Where to start? At the beginning or shall i dip into my fave presenters?

  • Sasha August 13, 2015, 12:18 pm
    Bob

    Received my copy this morning! :) Where to start? At the beginning or shall i dip into my fave presenters?

    Must admit I skipped the very technical stuff but I've gone through in order and am about to watch Fluge & Mella for the big finish!

  • wastwater August 14, 2015, 11:13 am

    Mine arrived yesterday,I liked the fluge and mella as I wasn't aware of cyclophosphamide.
    I'm encouraged as breast cancer and leukemia sit in the heart of my genetic risk chart,id also fit into the mega responder group.(just noticed something about Endothelial function too)
    High levels of interferon can produce a depressive/psychotic state maybe this is why its confusing for psychaitry

  • shahida August 14, 2015, 4:32 pm

    has anyone had problems with the DVD? I thought it waas my player but then i went on the laptop and it says it can't play ?????
    sorry i've sorted it- using wrong media player !!

  • Sasha August 14, 2015, 4:56 pm
    shahida

    has anyone had problems with the DVD? I thought it waas my player but then i went on the laptop and it says it can't play ?????

    Mine played fine on my DVD player.

  • bertiedog August 14, 2015, 6:47 pm

    Mine arrived today but I haven't had time to open it yet. Might save it for a rainy day!

    Pam

  • Bob August 15, 2015, 1:20 pm

    I've just watched Dr Mella's presentation and was fairly blown away by it despite having followed events closely and already knowing much of the info. I now understand what the attendees meant when they said that his presentation spoke 'quality'.

    When he was describing the rituximab trial I was mentally comparing it to the PACE trial and the contrast was surprisingly staggering and actually almost breath taking. I hadn't expected such a reaction, but the contrast was unexpectedly stark. (Note to self: We must NEVER let the psych lobby get away with questioning the quality of the rituximab trial. We must fight such attempts to undermine our lives and our future health care!)

    Huge efforts and extra expense has gone into the double blinding process to make sure the trial is extra water tight (whereas the PACE trial had no proper blinding.) Scrupulous efforts have been undertaken to make sure that there is a cut off point for data to be entered into the system so the data can't be adjusted, or added to, later. All end points are set in stone – there'll be no post hoc fiddling with the end points to suit the authors (as there was in the PACE trial.)

    Dr Mella said that all this attention to rigour is necessary so that the study will stand up to the highest standards of scrutiny e.g. by the FDA etc. (contrast this with the pace trial which has had zero scrutiny except from the patient community). Rigour is important if the trial is to be the most benefit to the patient community .

    The presentation oozes quality and rigour. And I think it's probably the most interesting presentation that I've watched from the conference so far. (But that's not a reflection on the other presentations.)

    It's not just the details of the rituximab trial that are interesting, but there are lots of various interesting little titbits of information. He gives a lot of interesting background about how the two doctors became involved in ME (interesting to hear it from the horses mouth, as the saying goes, rather than reading about it). And also interesting info about the direction that the two doctors are traveling and all the activities they are becoming involved in and extra projects and extra studies and how things are developing in Norway in general and what effect the rituximab trials have had on the public psyche. I think he suggested that it's had a profound effect in Norway. e.g. He's made presentations to government ministers, and is involved in unprecedented collaborations with medical institutes in Norway. Also interesting to hear that there are ongoing meaningful collaborations with e.g. UCL.

    I can't remember everything, and there's too much to convey it all here anyway, but it's really interesting. I'm going to watch it again today.

  • Sasha August 15, 2015, 1:32 pm

    What struck me about Dr Mella's presentation was that he said the Department of Health came to see him and told him they were going to give him money for the Phase III trial, without him even asking.

  • Bob August 16, 2015, 7:21 pm
    Sasha

    What struck me about Dr Mella's presentation was that he said the Department of Health came to see him and told him they were going to give him money for the Phase III trial, without him even asking.

    Some quotes for anyone interested:
    "The department of health in fact gave us money without us asking for it.
    That's quite an unusual situation – I've never had that before.
    It was just after the 2011 publication – then a minister of health came to our department and in fact over the table said: 'you're going to have this money for this'.
    That's not very usually seen.
    "

    Separately, they also applied competitively to the Norwegian Research Council for funds.

    And they applied to: "Regional health authorities – that's also through the Norwegian Research Council – in competition there – there were 70 applications for multi-regional studies and we were one of the ten selected, so we're also proud of that."

    He also mentions and thanks the MEandYou crowdfund and the Norwegian ME Association and others, including the Kavli Foundation.

  • Bob August 16, 2015, 8:26 pm

    Some brief notes on Dr Mella's presentation.

    I can only make notes on a small portion of the presentation because it's such a long presentation, filled with very interesting and detailed info. And it's very fiddly using my software to pause and rewind etc.
    But i've tried to pick out a few interesting tidbits that i haven't come across elsewhere.

    Collaboration and cooperation

    They seem to be gaining quite a lot of interest in ME from people and institutes who haven't previously been interested in ME, for example including the directorate of health with whom he has had meetings.

    Other examples are: cooperation with dept of immunology at the national hospital in Oslo.
    Collaboration with five different hospitals, including four university hospitals – which is "quite unique".
    He says his oncology colleagues are getting interested in ME – "it's quite interesting".
    Gastroenterologists are involved in the research, and have become "quite interested".
    They are supported, in a big way, by the Kavli Foundation, a charitable institution.
    Other Norwegian institutes have become interested and are working collaboratively.

    They've also had collaboration with UCL and investigators in Berlin and others.
    Plus they are working collaboratively with others.

    Endothelial Dysfunction hypothesis

    Endothelial Dysfunction hypothesis – Inability to respond with dilation of vessels to adequate stimuli. He mentions a study from Dundee published a few years ago, that demonstrated this phenomenon in ME patients. This phenomenon is measured in large vessels by flow mediated vasodilation – ultrasound measurement. They are also investigating micro-vessels via a slightly different method. They have found 'certain' evidence for endothelial dysfunction in preliminary research and he seems to be convinced (i.e. 'certain') that this is a real phenomena and that the degree of dysfunction correlates to disease severity. They are testing this in further studies, as part of the phase iii rituximab trial.

    Gastro-Intestinal function

    A sub-study for gastro-intestinal function for patients with gastrointestinal symptoms as a major part of their clinical presentation. Gastroenterologists have become "quite interested" and will do functional tests (including endoscopy with biopsies, a test meal, and endoscopic ultrasound) before and after rituximab intervention. (It's interesting that they are doing biopsies, but there was no mention of what they will test for in the biopsies.) They want to see if the patients' reported symptoms are objectively measurable at different time points during the rituximab trial. No further details were given.

    Projected response rates in the Phase iii Rituximab trial

    They're hoping, based on educated intuition, to get not less than a 50% response rate in the phase iii trial. These lower expectations are because a lower response rate is often seen in phase iii trials. They are also expecting a placebo response rate of 20% in the phase iii trial – also lower than the phase ii trial.

    Characteristics of Responders and non-responders

    They're looking for characteristics of responders and non-responders such that they can make predictions about whether patients will response to Rituximab or not.

    Transient Deterioration after Rituximab Infusions

    The transient deterioration in some patients happened immediately during (i think he said 'during', but i need to double check this) and after rituximab infusion, which he said was interesting from a mechanistic point of view.

    Biobank

    They have created a biobank from which samples and data can be used for years, and can be shared with co-investigators locally and abroad.

    Public Interest and changing attitudes

    "And we have got a lot of public interest, which has been important for how ME is looked upon in the country. And very many of the patients say that."
    "And I've been invited to the directorate of health, for example, and had lectures for them, and that wouldn't have happened a few years ago."

    Kavli Foundation

    The Kavli foundation, a charitable philanthropic foundation, approached them in 2011, and are a "life-line" – They provide money for laboratory costs and mechanistic studies. It seems that they are providing substantial support for various research work with ME/CFS. And they seem to be funding Dr Fluge to research ME/CFS, so he can take time away from his oncology commitments, if i understood that correctly.

    Thank-you

    "I'd particularly like to say thank you to Invest in ME for inviting us, and also for this very nice meeting. I would say we have been here for five years, Øystein and I, and this is the best meeting until now. The quality of the meeting has improved, and i'm especially impressed by the researcher meeting, which is getting better and better each year. so thank you very much for that."

    "And also thank you to all our patients. Those who are here and those who aren't here.
    Because Most of our ideas are in fact derived from listening to patients.
    It's a good thing for doctors to listen to patients [*cheers and applause*] because what they tell us is the truth."
    It's our problem to try to derive what is underlying what they tell us.
    What mechanisms are underlying what they tell us.
    Because what they tell us is in fact what is happening to them, and that has a cause.
    So it's up to us to find out what that was.
    "

    Cyclophosphamide

    Dr Mella also discusses the phase ii study of 40 ME patients for cyclophosphamide, which they are carrying out with their other oncology colleagues within their hospital, but i don't think there's any new info there. 12 month follow up. At least mild-moderate disease severity. If good response and acceptable toxicity then a further 20 severely affected patients will be studied.

    Other Research

    "We are doing a lot of studies that haven't been published yet – There will be interesting studies coming out in the years to come."

    Slide: "We believe that understanding better the underlying disease mechanisms more clearly is imperative: therefore sub-studies and laboratory studies."
    "The greatest problem is to try to figure out what are primary (giving debilitating symptoms) and what are secondary (partly compensatory) phenomena."
    "Therefore we look into:
    "Immunological abnormalities (autoimmune or auto-inflammatory process specific autoantibodies?)
    "Genome analysis in families with predisposition for ME: clues to which system that may be affected by the on-going immune process?
    "What is wrong with auto-regulation of blood vessel tonus, giving blood perfusion problems (= lack of increased blood supply when needed)?
    "How is cell metabolism (including nutrient uptake and utilization) influenced by the immune process (in vitro analysis – patient serum)?"

  • Kati August 16, 2015, 9:01 pm

    Thank you so much @Bob I really apprecieate this. i used to buy the DVD every year but for the last 2years the DVD's are only available in a format that is not compatible with the american computers so I haven't bought them.

  • shahida August 19, 2015, 5:48 pm

    Did anyone think the Betsy keller one inappropriate- im moderately affected but couldnt do those exercises. Most are struggling just to keep fed and clean. The people she must see must be v. high ly funtioning. But she didnt seemn aware of this- just extrapolated to everyone with ME. I wouldnt show this dvd to my doc' as they're likely to get the wrong impression. Might send some feedback to Iime on this.
    If anyone has any thoughts on this i'd be v. interested to hear/read.

  • Scarecrow August 19, 2015, 5:57 pm
    Dr Mella

    "And also thank you to all our patients. Those who are here and those who aren't here.
    Because Most of our ideas are in fact derived from listening to patients.
    It's a good thing for doctors to listen to patients [*cheers and applause*] because what they tell us is the truth."
    It's our problem to try to derive what is underlying what they tell us.
    What mechanisms are underlying what they tell us.
    Because what they tell us is in fact what is happening to them, and that has a cause.
    So it's up to us to find out what that was."

    Neatly demonstrating in yet another way how they compare favourably to the PACE investigators.