13 ms·

Scientists Edge Closer To Lab Test For Chronic Fatigue Syndrome

284 points by iamjeff 9y ago

carbocation 9y ago
The article is here: http://www.pnas.org/content/early/2017/07/25/1710519114.full.pdf http://www.pnas.org/content/early/2017/07/25/1710519114.full... It's worth noting that their false discovery rate was not study-wide, but rather group-wide. As they state at the very end of the paper, "FDR control was performed separately by group (e.g., severity level) to allow for group differences in the proportions of truly null hypotheses". So, if you try to look at all significant P-values, after adjustment, you'll find that for that purpose, the P-value significance is going to be inflated.
- iamjeff 9y ago
  Also, might be of interest to head over to the supplemental information: http://www.pnas.org/content/suppl/2017/07/25/1710519114.DCSupplemental/pnas.1710519114.sapp.pdf http://www.pnas.org/content/suppl/2017/07/25/1710519114.DCSu... ...p. 4 esp: 1) Analysis of ME/CFS Cases vs. Healthy Controls (case versus control means comparisons): We employed pseudo-likelihood ratio testing (8)2 to compare pMFI means between a) each disease severity group versus control and b) the equally-weighted average across all three severity groups versus control.
- jdietrich 9y ago
  It's also worth noting that there is no clear causal relationship. There is a strong and well-established association between depression and inflammatory biomarkers, but we have very little idea of whether depression increases the risk of inflammatory illness or vice-versa. http://www.mdedge.com/currentpsychiatry/article/76288/depression/depression-and-inflammation-examining-link http://www.mdedge.com/currentpsychiatry/article/76288/depres...
  - Reason077 9y ago
    You'd think the answer would be easy to figure out. If you successfully treat the inflammatory illness, does the depression go away?
    - smallnamespace 9y ago
      > If you successfully treat the inflammatory illness How do you know you completely succeeded?
      - jonlucc 9y ago
        This is not my field, but you can measure inflammation a couple of ways. One is by quantifying cytokines present and another one is to count blood cells.
    - jdietrich 9y ago
      The answer to that question just muddies the waters further. Anti-inflammatory drugs have been shown to have some anti-depressant effect, while anti-depressant drugs have been shown to have some anti-inflammatory effect. In both cases, the effect size is fairly small. It would be nice to find a simple cure for a complex and diffuse set of symptoms, but we haven't had any luck so far. In all likelihood there are multiple interacting factors that affect the progression of depressive disorders, with no singular cause. http://www.nature.com/mp/journal/vaop/ncurrent/full/mp2016167a.html?foxtrotcallback=true http://www.nature.com/mp/journal/vaop/ncurrent/full/mp201616... https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3194072/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3194072/
  - joools 9y ago
    The research I'm familiar with (and teach) suggests you see associations prospectively in both directions, but no clear evidence of causality (although I've grown skeptical of causality as a concept). This PNAS paper is nice to see, although as some are pointing out, there's a bit of p-hacking probably going on. My sense is that certain research topics are kind of ground zero in this misled, outdated mind-body war. So you see people trying to demonstrate something along the lines of "see here, there's a biological basis to this, so patients aren't just inventing this," as if the psychosomatic conceptualization of the problem was ever just "inventing it," and as if people with psychogenic psychosomatic problems can't mimic the same things in their subjective reports (what happens when you do have this cytokine screen, and you still have people who look normal on that?) As you're alluding to here, the problem is that even if you do find inflammation markers it's difficult to tell if this is due to stress in a broad sense, and how these markers relate to perceptions of stress across a broad range of individuals. Just to take an example: how do these markers look in psychiatric patients who don't report CFS symptoms? I don't mean to suggest that these individuals have psychiatric problems, but it's unclear to me from this study what is going on with these inflammatory markers. Let's say these cytokines do cause increased pain and fatigue experience. Do CFS patients have a stronger relationship between those inflammatory markers and experienced pain? If so, what does that mean? The paper itself is more appropriate in tone than the NPR article, for what it's worth.
    - JPLeRouzic 9y ago
      I am at the half of this long thread, comments are incredibly good and interesting --even for HN-- but yours seems to me outstanding. Thanks for taking the time to write it.
    - pablobaz 9y ago
      Many CFS studies use patients with depression as a control for the very reasons you have suggested.
- Real_S 9y ago
  If you follow their methods, specifically [63], they are modelling the proportion of null hypotheses in their tests. Performing FDR by group is a reasonable approach, and does not necessarily cause P-value inflation. This is different from a Bonferroni correction, in which total numbers of tests done is the only factor. These FDR models of the proportion of null hypotheses rely on the distribution of p-values, not their raw count (assuming a sufficient count of P-values is present in which to model). Dividing the FDR correction as they did provides more information about group-specific influences, and should not be considered p-value hacking. Nevertheless, thank you for calling this out. There is way too much p-hacking in science, especially biology. [63] Benjamini Y, Krieger AM, Yekutieli D (2006) Adaptive linear step-up procedures that control the false discovery rate. Biometrika 93:491–507.
  - carbocation 9y ago
    Right. My point is actually that they're doing an FDR within each group, not across the whole study. So, the adjusted P values are accurate within each group, but to look globally, you either need to then Bonferroni or re-perform the FDR globally. I'm not saying that my point is in disagreement with yours, by the way, I'm just trying to clarify that my point is independent of whether they had done in-group FDR or in-group Bonferroni. I actually built an online FDR calculator previously, since I enjoy the topic so much: https://tools.carbocation.com/FDR https://tools.carbocation.com/FDR
andreasklinger 9y ago
Does anyone have more information on this topic? I am never sure if this is snake oil market or not.
peteyPete 9y ago
I can only hope/wish for some advancement in CFS/ME.. Having a loved one who has it makes you see how hopeless many people have been for so long and how little the healthcare system has been able to help. Really hope to see change soon.
- cpncrunch 9y ago
  Yes, at the moment doctors aren't really much help. However there are various things you can do yourself as a CFS patient to improve things, and possibly recover. I suffered from CFS myself and recovered about 17 years ago (with no relapses since), so it is possible.
revscat 9y ago
Can I ask an honest, albeit admittedly cynical, question? In a world run by libertarian capitalists, what good comes from such studies? I know such things can be used to determine policy. But let's say that in turns out cytokines do, in fact, cause CFS, and that -- for the sake of argument -- banning them would be a good thing. How would this newfound knowledge go from being something known to having action taken upon it? Libertarian capitalism has come to dominate every discussion of this kind. If an action requires regulatory or legislative action, the modern capitalist opposes it outright, even if the outcome would be demonstrably good. Please forgive if this is off-topic, but it is frustrating seeing such well-done science that seemingly has no one of similar professionalism in the political realm to apply that knowledge in a way that makes society better off.
- camillomiller 9y ago
  That's not so true in Germany, or in Europe in general
- ivraatiems 9y ago
  I don't think of myself as a libertarian capitalist, or anything close to that, but I think that being one does not preclude one from playing the long game. One can certainly decide that they will gain maximum profit by investing heavily in research that doesn't have an immediate practical result now, betting on the idea that over time, that research will see a return. For instance, suppose that the cure for this problem turns out to be an expensive, complex drug. Somebody stands to make a lot of money by figuring out what that drug is and selling it. They can't make that money now, but eventually they'll be able to, so they support the research in order to get there. Now, do I support profit being the driver behind this kind of research? Not at all. Do I think it's the best system for doing this? Hardly. But can it work? It can and sometimes does.
- pfisch 9y ago
  Are you a bot or a real person? How could you ban cytokines? That doesn't even mean anything to the point where I'm not sure you are a human author.
  - 9y ago
propman 9y ago
If someone comes to you with a whole lot of pain and loss of function, ignoring it and thinking it's just in their head/they just need to toughen up and get over it because nothing showed up in thier blood reports is something that is almost ubiquitous in the medical field today. I have a connective tissue disorder that was ignored for years because nothing showed up in my blood report and I looked healthy. There is a reason why people are dysfunctional and in pain and once I got a diagnosis from a very highly respected geneticist, every doctor believes you and then they start helping. Otherwise, many just brush you off or worse, perform a surgery and when you keep coming back due to little change in symptoms you get brushed off so you find another doctor, in their minds they successfully treated you and the same cycle continues until you find a doctor who listens and then the treatment essentially starts. Glad to see CFS sufferers get some validation as they are ignored plenty of times, especially women sufferers. Note: I would say 40% of my doctors (I've seen over 50) were not like this and about 20% were over the top amazing. Acccesible through phone or email anytime, personally call you after appointments and intermittently to check up, personally call other doctors to explain issues and follow up treatments, extra long appointments. Basic message: if someone is in pain/unhealthy there is a reason. Rarely it is psychological but that doesn't mean they should not receive adequate treatment and that doesn't mean you place them in that category unless you rule out plenty of other possibilities
- tomcam 9y ago
  MD's are by and large incredibly non-curious about hard-to-diagnose chronic conditions
  - o_____________o 9y ago
    What incentive do they have besides being a heroic, indefatigable person? If anything, they're increasing their attack surface for being blamed or sued.
    - komali2 9y ago
      Curious about this. I often find engineers motivated purely by the desire to solve the problem. Was just at defcon - witnessed many people vaguely wandering around the tables of teams trying to hack devices, then getting sucked in as they offered solutions and inevitably got involved with trying to solve the problem. Did it myself a couple times, even though I had planned on attending more talks.
mudil 9y ago
I am an MD, born in Russia, but did medical school here in the United States. All the same, people constantly ask about the Russian medicine, and so I was recently asked if we have fibromyalgia in Russia. My answer was that I don't know about fibromyalgia. But what I know is that half of the psychotropic drugs that people are prescribed in this country we only give to political prisoners in Russia.
- pault 9y ago
  Can you elaborate? Why are political prisoners medicated?
  - azernik 9y ago
    Not GP, but I can elaborate a bit. It was common Soviet practice in the post-Stalin era to, instead of explicitly arresting political dissidents, to classify them as insane and have them involuntarily committed. Looks less bad than calling it a jail. I haven't heard of this practice being continued in post-communist Russia, but I wouldn't be enormously surprised to hear that it was.
- dEnigma 9y ago
  How do you know this? Has the Russian government a public list of psychotropic drugs it uses on its political prisoners?
  - mudil 9y ago
    Right, Russian government publishes a list of psychotropic substances that are given to political prisoners. Jeez, people, it's a joke. The joke is a commentary about American proclivity to eat psychotropic meds like vitamins.
    - dEnigma 9y ago
      I was under the impression that you seriously thought you knew which drugs the Russian government uses on its prisoners and was making a tongue-in-cheek remark in response.
Mz 9y ago
There are an awful lot of online discussion groups for various medical problems. It is not uncommon for members to share new research in hopes of better understanding their own condition. In some cases, they are pursuing alternative remedies because conventional treatment and proven science are failing them so badly. Getting solid information about what is likely actually happening in their own body can be empowering. It isn't the sort of thing most policy makers or business makers want to hear. People in such positions tend to be incredibly controlling and actively against the idea of empowering patients to take better care of themselves through better understanding of their condition. But it is actually a low cost, effective way to get better quality of life in the face of coping with a chronic, likely incurable, condition. Written in reply to this, which is now dead, so I cant post it there: https://news.ycombinator.com/item?id=14896446 https://news.ycombinator.com/item?id=14896446
dawhizkid 9y ago
Surprised no one has mentioned a Keto diet yet as a potential remedy for CFS. One of the biggest benefits of Keto is its anti-inflammatory effects. A quick Google search brings up at least a few research papers showing that Ketogenic diets have been seen to suppress the expression of inflammatory cytokines.
- jamesdftx 9y ago
  Just saw your other carbs comment, I agree. I've seen first hand the great improvements with Keto, but it's a very difficult diet to get into with the subsidies carb-heavy foods receive.
kens 9y ago
I looked at the paper and the data is kind of strange. Looking at figure 2, there are a bunch of cytokines that have a nice linear progression with increasing levels corresponding to increasing severity of disease. This seems like solid evidence that more cytokine = bad. But if you compare with the controls, mild cases of ME/CFS have less than the control, moderate cases have the same as controls, and severe cases have more. This kind of torpedoes any simple explanation of what's going on. The authors discuss this in a kind of hand-wavy way that maybe ME/CFS causes some down-regulation to start with and then the increasing trend is on top of that. So, I'm not sure what to make of this. It seems useless as a test at this point: "You have totally normal cytokine levels, indicating that you're either healthy or have moderate ME/CFS."
- Gibbon1 9y ago
  The thing that currently spazs me out is the Simpson Paradox (Yule–Simpson effect) https://en.wikipedia.org/wiki/Simpson%27s_paradox https://en.wikipedia.org/wiki/Simpson%27s_paradox In short, if your population has two (or more) diseases with similar enough symptoms that they are grouped together, statistical analysis can and does totally fail. And your experiment will produce garbage. So what if Chronic Fatigue Syndrome is really caused by a couple of different things, but with converging symptomology. You have a real catch 22 situation. Can't identify the cause of the disease without a consistent experimental group. Can't select a consistent experimental group without a functional test.
  - kens 9y ago
    That's a very good point. The paper suggests that "severity may be a key variable for subgrouping ME/CFS." So it's possible that there are three different ME/CFS diseases that can be distinguished by cytokine levels. Hopefully once these are separated, statistical analysis will succeed and medical progress would follow. In the bigger picture, you have to wonder how many things that we currently categorize as one disease are really many different diseases. (Like how in the 1800s, people would die of "a fever" but we now know there are many different diseases causing fevers.) It's kind of a cliche now that cancer is not a single disease. I expect conditions such as autism and schizophrenia will fragment once the right tests are available. What else?
mschuster91 9y ago
The problem is that once you "empower" people you also empower everything from straight out morons to manipulative sociopaths - which has led from relatively harmless homeopathic "medicine" (which is harmless but many people use homeopathic medicine even for serious illness and go to the doctor only when it's unbearable), to the rise of anti-vax movement (where lots of kids actually even died from measles exposure in the last few years) and finally people consuming deadly sodium chlorite (aka MMS). Allowing people to take health purely into their own hands leads down to a very dangerous path, especially when children are involved (as children cannot help themselves against ignorant parents).
- Mz 9y ago
  Allowing people to take health purely into their own hands leads down to a very dangerous path I said nothing whatsoever to adovocate allowing such a thing. But thank you for providing evidence of my statement about how controlling a lot of people want to be when it comes to such topics.
  - mschuster91 9y ago
    > But thank you for providing evidence of my statement about how controlling a lot of people want to be when it comes to such topics. In most areas I tend to be a libertarian - but not when single stupid decisions can affect other innocent people. Fine with me if you want to kill yourself with measles, but leave other people out of this mess. People refusing vaccinations are a threat to society, and should be exiled in my opinion. As a matter of fact, many countries have shifted to exiling the kids from school when unvaxed in order to combat both the antivax movement and the exploding numbers of (mostly) measles infection. Measles has the very real potential of killing you (or your child), and up to 30% of cases get severe complications as a result. Remember that the antivax movement basically was hyped up by that Wakefield study? This is something that should not even have been published. It should have been eradicated from the history books.
    - Mz 9y ago
      Wow, you are completely twisting everything I have said. So twisting it that engaging you in good faith is essentially impossible. You are basically determined to tar and feather me, and never mind what I actually said.
inopinatus 9y ago
"Do you know what they call 'alternative medicine' that's been proved to work? Medicine." - Tim Minchin, Storm, 2008. Should you trust an authority? That is always a personal decision. I try not to, but I will listen to someone with credentials and give weight to their knowledge and experience. Online randoms describing an "alternative" are not challenging authority or bypassing it: no matter how they try to frame it, they are trying on the mantle of authority itself, but with no foundation. Your assertion that "policy makers" are systematically withholding "solid information about your body" is paranoid nonsense. If you want to go study the systems of your body, all the world's medical information is publicly available. There's a reason a medical degree takes seven years or more, however: the body of knowledge is vast and interconnected. It's not withheld, it's just a much greater challenge than many of us are willing to undertake. Online forums may be a source of good advice and anecdotal suggestions, but they also give false hope to the desperate, and thereby open the window to perpetuating snake oil and quackery and delusional magical thinking. At their worst, this amounts to conducting uncontrolled medical experiments on other human beings who are only willing because they are desperate - and that's close to evil in my book.
- Mz 9y ago
  Your assertion that "policy makers" are systematically withholding "solid information about your body" is paranoid nonsense. I said nothing of the sort. Both of the replies to me seem to be reading in enormous amounts of bs that isn't in my remark at all. Patients being informed about their condition is not all about people promoting snake oil. For some conditions, the patients themselves are often better informed than general MDs. Only actual specialists in the condition really know more and going to a general MD with no experience in their specific condition sometimes has catastrophic (even deadly) results.
  - inopinatus 9y ago
    You said everything of that sort. If that was not your intent, then perhaps in future you might say what you mean, rather than defending the vendors of false hope and perpetuating the extremely harmful myth that one can treat oneself. As in this: > patients themselves are often better informed than general MDs No, that is a gross overgeneralisation and not true of any condition. A few patients may have slightly better information in one dimension of their condition than a GP. Presuming otherwise is foolhardy arrogance that misses the profound interconnectedness and subtle complexity of body systems. And this is especially the case with endocrine and immune systems. Patients should be as informed as possible, yes, because this is always a benefit to one's treatment. Crossing the line into "I-know-better"-land is arrogance and idiocy.
tomhoward 9y ago
There seems to be a desire evident in the commentary on this topic to categorise CFS as either completely psychological, or completely physiological. My own experience, having had the condition for much of the past 10 years, and having (after many years of frustration) found treatment methods that have enabled me to achieve almost full recovery, is that it is very much both physiological and psychological, and that only by treating the mind and the body together can full recovery be achieved. Whilst many people will want to read this study as evidence that CFS is fundamentally physiological in nature, it doesn't do anything to dismiss the role of psychology as a causal or perpetuating factor. It is equivalent to using a lab test indicating (for example) imbalances of serotonin as evidence of depression, without taking into account the many years of stress and trauma that may have led up to the issue manifesting as a physiological (and debilitating psychological) condition. Whilst I have no doubt there is scope to develop treatments that can ease CFS sufferers' physiological symptoms, and I hope research findings like this can help to bring about these kinds of breakthroughs, I have no expectation that a comprehensive remedy for CFS can be found that doesn't include profound psychological healing as a key part of the treatment. It also occurs to me that a major reason why this condition continues to evade explanation and treatment by mainstream medicine, is that the profession is unaccustomed to looking at things as both psychological and physiological in nature, and that it will take a change in mindset on this to pave the way to discovering effective treatments for CFS and other such "mysterious" conditions.
- cpncrunch 9y ago
  My experience, having fully recovered, is similar, and it fits with what we know about how the brain works.
- gerbilly 9y ago
  What treatments did you discover?
Nightshaxx 9y ago
As someone who has suffered from CFS I am so happy to see it becoming more recognized and understood. You see, the frustrating part of having an illness like this is it is not well known enough for people to really understand it, but it has major impacts on your life. I can't tell you how utterly angring it is to be sitting in front of my computer and I know that if I just finish this school paper that isn't anything that hard, I can go to that social event, but I just am so tired I can't do it.
- fcoury 9y ago
  As someone whose symptoms fits the bill, how did you get diagnosed and how did you get it under control?
  - GFischer 9y ago
    Be careful, those symptoms are also for a lot of other things including depression and burnout which are far more common amongst programmers. Do get diagnosed and get a second opinion, but it might or might not be CFS.
inieves 9y ago
CFS is most likely "Candidasis". An overgrowth of candida bacteria/yeast in the gut. This is very well known, and easily and cost effectively treatable. Consistent overconsumption of processed sugars leads to candida overgrowth. The body addresses this naturally through inflamation. Prolonged inflamation yields depression symptoms, and a host of other things. Google: candida You can recover from this mostly in one night for $5 and fully in about 2 weeks for $30. Ultimately these Stanford guys will try to design and patent an anti-inflammitory and it will cost you alot and not solve the problem. Address the source of inflammation. Im surprised no one in this thread knows this and debate has wandered into little to no value. If you are suffering from this, please please research candidasis or candida cleanse.
- rfugger 9y ago
  This study suggests that candida is probably not the culprit: https://www.ncbi.nlm.nih.gov/pubmed/18339054 https://www.ncbi.nlm.nih.gov/pubmed/18339054
- Smaug123 9y ago
  The trouble with this kind of comment is that I can find scores of people who say that CFS (and fibromyalgia) is most likely a misdiagnosed hypothyroidism, treatable with standard T3/T4. Lots of people say "it's obviously <this thing> treatable in <this cheap way>" for some value of <this thing>, and that makes them all less credible.
- Kudos 9y ago
  FWIW, this did not work for me.
visarga 9y ago
If you're feeling fatigued, try Calcium and Magnesium supplements. They're cheap and safe and you might simply have a lack of minerals that doesn't show up in blood tests. That's what it was for me anyway. From chronic fatigue to normal life - it feels like I took 15 years off. Calcium relieves muscle pains, Magnesium improves sleep and reduces stress. They can also have a laxative effect.
hellofunk 9y ago
I'm not sure if it's me or the article, but something about reading it just made me really tired. More so than, say, Javascript fatigue. Which is interesting, because usually that's my limit.
cpncrunch 9y ago
Here is why CFS research is so difficult: https://news.ycombinator.com/item?id=14896929 https://news.ycombinator.com/item?id=14896929
cpncrunch 9y ago
Some commentary on this study by experts: http://www.sciencemediacentre.org/expert-reaction-to-cytokines-for-chronic-fatigue-syndrome/ http://www.sciencemediacentre.org/expert-reaction-to-cytokin... In summary: - it's quite overhyped. - we already knew that TGF-B was elevated in patients. - as TGF-B wasn't increased after exercise, that puts into question how relevant it is as a biomarker, as symptoms tend to increase after exercise. - it doesn't give any indication as to whether the illness is organic or psychological, as both depression and lack of sleep cause inflammation.

284 points by iamjeff 9y ago

The article is here: http://www.pnas.org/content/early/2017/07/25/1710519114.full.pdf http://www.pnas.org/content/early/2017/07/25/1710519114.full... It's worth noting that their false discovery rate was not study-wide, but rather group-wide. As they state at the very end of the paper, "FDR control was performed separately by group (e.g., severity level) to allow for group differences in the proportions of truly null hypotheses". So, if you try to look at all significant P-values, after adjustment, you'll find that for that purpose, the P-value significance is going to be inflated.

iamjeff 9y ago
Also, might be of interest to head over to the supplemental information: http://www.pnas.org/content/suppl/2017/07/25/1710519114.DCSupplemental/pnas.1710519114.sapp.pdf http://www.pnas.org/content/suppl/2017/07/25/1710519114.DCSu... ...p. 4 esp: 1) Analysis of ME/CFS Cases vs. Healthy Controls (case versus control means comparisons): We employed pseudo-likelihood ratio testing (8)2 to compare pMFI means between a) each disease severity group versus control and b) the equally-weighted average across all three severity groups versus control.
jdietrich 9y ago
It's also worth noting that there is no clear causal relationship. There is a strong and well-established association between depression and inflammatory biomarkers, but we have very little idea of whether depression increases the risk of inflammatory illness or vice-versa. http://www.mdedge.com/currentpsychiatry/article/76288/depression/depression-and-inflammation-examining-link http://www.mdedge.com/currentpsychiatry/article/76288/depres...
- Reason077 9y ago
  You'd think the answer would be easy to figure out. If you successfully treat the inflammatory illness, does the depression go away?
  - smallnamespace 9y ago
    > If you successfully treat the inflammatory illness How do you know you completely succeeded?
    - jonlucc 9y ago
      This is not my field, but you can measure inflammation a couple of ways. One is by quantifying cytokines present and another one is to count blood cells.
  - jdietrich 9y ago
    The answer to that question just muddies the waters further. Anti-inflammatory drugs have been shown to have some anti-depressant effect, while anti-depressant drugs have been shown to have some anti-inflammatory effect. In both cases, the effect size is fairly small. It would be nice to find a simple cure for a complex and diffuse set of symptoms, but we haven't had any luck so far. In all likelihood there are multiple interacting factors that affect the progression of depressive disorders, with no singular cause. http://www.nature.com/mp/journal/vaop/ncurrent/full/mp2016167a.html?foxtrotcallback=true http://www.nature.com/mp/journal/vaop/ncurrent/full/mp201616... https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3194072/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3194072/
- joools 9y ago
  The research I'm familiar with (and teach) suggests you see associations prospectively in both directions, but no clear evidence of causality (although I've grown skeptical of causality as a concept). This PNAS paper is nice to see, although as some are pointing out, there's a bit of p-hacking probably going on. My sense is that certain research topics are kind of ground zero in this misled, outdated mind-body war. So you see people trying to demonstrate something along the lines of "see here, there's a biological basis to this, so patients aren't just inventing this," as if the psychosomatic conceptualization of the problem was ever just "inventing it," and as if people with psychogenic psychosomatic problems can't mimic the same things in their subjective reports (what happens when you do have this cytokine screen, and you still have people who look normal on that?) As you're alluding to here, the problem is that even if you do find inflammation markers it's difficult to tell if this is due to stress in a broad sense, and how these markers relate to perceptions of stress across a broad range of individuals. Just to take an example: how do these markers look in psychiatric patients who don't report CFS symptoms? I don't mean to suggest that these individuals have psychiatric problems, but it's unclear to me from this study what is going on with these inflammatory markers. Let's say these cytokines do cause increased pain and fatigue experience. Do CFS patients have a stronger relationship between those inflammatory markers and experienced pain? If so, what does that mean? The paper itself is more appropriate in tone than the NPR article, for what it's worth.
  - JPLeRouzic 9y ago
    I am at the half of this long thread, comments are incredibly good and interesting --even for HN-- but yours seems to me outstanding. Thanks for taking the time to write it.
  - pablobaz 9y ago
    Many CFS studies use patients with depression as a control for the very reasons you have suggested.
Real_S 9y ago
If you follow their methods, specifically [63], they are modelling the proportion of null hypotheses in their tests. Performing FDR by group is a reasonable approach, and does not necessarily cause P-value inflation. This is different from a Bonferroni correction, in which total numbers of tests done is the only factor. These FDR models of the proportion of null hypotheses rely on the distribution of p-values, not their raw count (assuming a sufficient count of P-values is present in which to model). Dividing the FDR correction as they did provides more information about group-specific influences, and should not be considered p-value hacking. Nevertheless, thank you for calling this out. There is way too much p-hacking in science, especially biology. [63] Benjamini Y, Krieger AM, Yekutieli D (2006) Adaptive linear step-up procedures that control the false discovery rate. Biometrika 93:491–507.
- carbocation 9y ago
  Right. My point is actually that they're doing an FDR within each group, not across the whole study. So, the adjusted P values are accurate within each group, but to look globally, you either need to then Bonferroni or re-perform the FDR globally. I'm not saying that my point is in disagreement with yours, by the way, I'm just trying to clarify that my point is independent of whether they had done in-group FDR or in-group Bonferroni. I actually built an online FDR calculator previously, since I enjoy the topic so much: https://tools.carbocation.com/FDR https://tools.carbocation.com/FDR

andreasklinger 9y ago

Does anyone have more information on this topic? I am never sure if this is snake oil market or not.

peteyPete 9y ago

I can only hope/wish for some advancement in CFS/ME.. Having a loved one who has it makes you see how hopeless many people have been for so long and how little the healthcare system has been able to help. Really hope to see change soon.

cpncrunch 9y ago
Yes, at the moment doctors aren't really much help. However there are various things you can do yourself as a CFS patient to improve things, and possibly recover. I suffered from CFS myself and recovered about 17 years ago (with no relapses since), so it is possible.

revscat 9y ago

Can I ask an honest, albeit admittedly cynical, question? In a world run by libertarian capitalists, what good comes from such studies? I know such things can be used to determine policy. But let's say that in turns out cytokines do, in fact, cause CFS, and that -- for the sake of argument -- banning them would be a good thing. How would this newfound knowledge go from being something known to having action taken upon it? Libertarian capitalism has come to dominate every discussion of this kind. If an action requires regulatory or legislative action, the modern capitalist opposes it outright, even if the outcome would be demonstrably good. Please forgive if this is off-topic, but it is frustrating seeing such well-done science that seemingly has no one of similar professionalism in the political realm to apply that knowledge in a way that makes society better off.

camillomiller 9y ago
That's not so true in Germany, or in Europe in general
ivraatiems 9y ago
I don't think of myself as a libertarian capitalist, or anything close to that, but I think that being one does not preclude one from playing the long game. One can certainly decide that they will gain maximum profit by investing heavily in research that doesn't have an immediate practical result now, betting on the idea that over time, that research will see a return. For instance, suppose that the cure for this problem turns out to be an expensive, complex drug. Somebody stands to make a lot of money by figuring out what that drug is and selling it. They can't make that money now, but eventually they'll be able to, so they support the research in order to get there. Now, do I support profit being the driver behind this kind of research? Not at all. Do I think it's the best system for doing this? Hardly. But can it work? It can and sometimes does.
pfisch 9y ago
Are you a bot or a real person? How could you ban cytokines? That doesn't even mean anything to the point where I'm not sure you are a human author.
- 9y ago

propman 9y ago

If someone comes to you with a whole lot of pain and loss of function, ignoring it and thinking it's just in their head/they just need to toughen up and get over it because nothing showed up in thier blood reports is something that is almost ubiquitous in the medical field today. I have a connective tissue disorder that was ignored for years because nothing showed up in my blood report and I looked healthy. There is a reason why people are dysfunctional and in pain and once I got a diagnosis from a very highly respected geneticist, every doctor believes you and then they start helping. Otherwise, many just brush you off or worse, perform a surgery and when you keep coming back due to little change in symptoms you get brushed off so you find another doctor, in their minds they successfully treated you and the same cycle continues until you find a doctor who listens and then the treatment essentially starts. Glad to see CFS sufferers get some validation as they are ignored plenty of times, especially women sufferers. Note: I would say 40% of my doctors (I've seen over 50) were not like this and about 20% were over the top amazing. Acccesible through phone or email anytime, personally call you after appointments and intermittently to check up, personally call other doctors to explain issues and follow up treatments, extra long appointments. Basic message: if someone is in pain/unhealthy there is a reason. Rarely it is psychological but that doesn't mean they should not receive adequate treatment and that doesn't mean you place them in that category unless you rule out plenty of other possibilities

tomcam 9y ago
MD's are by and large incredibly non-curious about hard-to-diagnose chronic conditions
- o_____________o 9y ago
  What incentive do they have besides being a heroic, indefatigable person? If anything, they're increasing their attack surface for being blamed or sued.
  - komali2 9y ago
    Curious about this. I often find engineers motivated purely by the desire to solve the problem. Was just at defcon - witnessed many people vaguely wandering around the tables of teams trying to hack devices, then getting sucked in as they offered solutions and inevitably got involved with trying to solve the problem. Did it myself a couple times, even though I had planned on attending more talks.

mudil 9y ago

I am an MD, born in Russia, but did medical school here in the United States. All the same, people constantly ask about the Russian medicine, and so I was recently asked if we have fibromyalgia in Russia. My answer was that I don't know about fibromyalgia. But what I know is that half of the psychotropic drugs that people are prescribed in this country we only give to political prisoners in Russia.

pault 9y ago
Can you elaborate? Why are political prisoners medicated?
- azernik 9y ago
  Not GP, but I can elaborate a bit. It was common Soviet practice in the post-Stalin era to, instead of explicitly arresting political dissidents, to classify them as insane and have them involuntarily committed. Looks less bad than calling it a jail. I haven't heard of this practice being continued in post-communist Russia, but I wouldn't be enormously surprised to hear that it was.
dEnigma 9y ago
How do you know this? Has the Russian government a public list of psychotropic drugs it uses on its political prisoners?
- mudil 9y ago
  Right, Russian government publishes a list of psychotropic substances that are given to political prisoners. Jeez, people, it's a joke. The joke is a commentary about American proclivity to eat psychotropic meds like vitamins.
  - dEnigma 9y ago
    I was under the impression that you seriously thought you knew which drugs the Russian government uses on its prisoners and was making a tongue-in-cheek remark in response.

Mz 9y ago

There are an awful lot of online discussion groups for various medical problems. It is not uncommon for members to share new research in hopes of better understanding their own condition. In some cases, they are pursuing alternative remedies because conventional treatment and proven science are failing them so badly. Getting solid information about what is likely actually happening in their own body can be empowering. It isn't the sort of thing most policy makers or business makers want to hear. People in such positions tend to be incredibly controlling and actively against the idea of empowering patients to take better care of themselves through better understanding of their condition. But it is actually a low cost, effective way to get better quality of life in the face of coping with a chronic, likely incurable, condition. Written in reply to this, which is now dead, so I cant post it there: https://news.ycombinator.com/item?id=14896446 https://news.ycombinator.com/item?id=14896446

dawhizkid 9y ago

Surprised no one has mentioned a Keto diet yet as a potential remedy for CFS. One of the biggest benefits of Keto is its anti-inflammatory effects. A quick Google search brings up at least a few research papers showing that Ketogenic diets have been seen to suppress the expression of inflammatory cytokines.

jamesdftx 9y ago
Just saw your other carbs comment, I agree. I've seen first hand the great improvements with Keto, but it's a very difficult diet to get into with the subsidies carb-heavy foods receive.

kens 9y ago

I looked at the paper and the data is kind of strange. Looking at figure 2, there are a bunch of cytokines that have a nice linear progression with increasing levels corresponding to increasing severity of disease. This seems like solid evidence that more cytokine = bad. But if you compare with the controls, mild cases of ME/CFS have less than the control, moderate cases have the same as controls, and severe cases have more. This kind of torpedoes any simple explanation of what's going on. The authors discuss this in a kind of hand-wavy way that maybe ME/CFS causes some down-regulation to start with and then the increasing trend is on top of that. So, I'm not sure what to make of this. It seems useless as a test at this point: "You have totally normal cytokine levels, indicating that you're either healthy or have moderate ME/CFS."

Gibbon1 9y ago
The thing that currently spazs me out is the Simpson Paradox (Yule–Simpson effect) https://en.wikipedia.org/wiki/Simpson%27s_paradox https://en.wikipedia.org/wiki/Simpson%27s_paradox In short, if your population has two (or more) diseases with similar enough symptoms that they are grouped together, statistical analysis can and does totally fail. And your experiment will produce garbage. So what if Chronic Fatigue Syndrome is really caused by a couple of different things, but with converging symptomology. You have a real catch 22 situation. Can't identify the cause of the disease without a consistent experimental group. Can't select a consistent experimental group without a functional test.
- kens 9y ago
  That's a very good point. The paper suggests that "severity may be a key variable for subgrouping ME/CFS." So it's possible that there are three different ME/CFS diseases that can be distinguished by cytokine levels. Hopefully once these are separated, statistical analysis will succeed and medical progress would follow. In the bigger picture, you have to wonder how many things that we currently categorize as one disease are really many different diseases. (Like how in the 1800s, people would die of "a fever" but we now know there are many different diseases causing fevers.) It's kind of a cliche now that cancer is not a single disease. I expect conditions such as autism and schizophrenia will fragment once the right tests are available. What else?

mschuster91 9y ago

The problem is that once you "empower" people you also empower everything from straight out morons to manipulative sociopaths - which has led from relatively harmless homeopathic "medicine" (which is harmless but many people use homeopathic medicine even for serious illness and go to the doctor only when it's unbearable), to the rise of anti-vax movement (where lots of kids actually even died from measles exposure in the last few years) and finally people consuming deadly sodium chlorite (aka MMS). Allowing people to take health purely into their own hands leads down to a very dangerous path, especially when children are involved (as children cannot help themselves against ignorant parents).

Mz 9y ago
Allowing people to take health purely into their own hands leads down to a very dangerous path I said nothing whatsoever to adovocate allowing such a thing. But thank you for providing evidence of my statement about how controlling a lot of people want to be when it comes to such topics.
- mschuster91 9y ago
  > But thank you for providing evidence of my statement about how controlling a lot of people want to be when it comes to such topics. In most areas I tend to be a libertarian - but not when single stupid decisions can affect other innocent people. Fine with me if you want to kill yourself with measles, but leave other people out of this mess. People refusing vaccinations are a threat to society, and should be exiled in my opinion. As a matter of fact, many countries have shifted to exiling the kids from school when unvaxed in order to combat both the antivax movement and the exploding numbers of (mostly) measles infection. Measles has the very real potential of killing you (or your child), and up to 30% of cases get severe complications as a result. Remember that the antivax movement basically was hyped up by that Wakefield study? This is something that should not even have been published. It should have been eradicated from the history books.
  - Mz 9y ago
    Wow, you are completely twisting everything I have said. So twisting it that engaging you in good faith is essentially impossible. You are basically determined to tar and feather me, and never mind what I actually said.

inopinatus 9y ago

"Do you know what they call 'alternative medicine' that's been proved to work? Medicine." - Tim Minchin, Storm, 2008. Should you trust an authority? That is always a personal decision. I try not to, but I will listen to someone with credentials and give weight to their knowledge and experience. Online randoms describing an "alternative" are not challenging authority or bypassing it: no matter how they try to frame it, they are trying on the mantle of authority itself, but with no foundation. Your assertion that "policy makers" are systematically withholding "solid information about your body" is paranoid nonsense. If you want to go study the systems of your body, all the world's medical information is publicly available. There's a reason a medical degree takes seven years or more, however: the body of knowledge is vast and interconnected. It's not withheld, it's just a much greater challenge than many of us are willing to undertake. Online forums may be a source of good advice and anecdotal suggestions, but they also give false hope to the desperate, and thereby open the window to perpetuating snake oil and quackery and delusional magical thinking. At their worst, this amounts to conducting uncontrolled medical experiments on other human beings who are only willing because they are desperate - and that's close to evil in my book.

Mz 9y ago
Your assertion that "policy makers" are systematically withholding "solid information about your body" is paranoid nonsense. I said nothing of the sort. Both of the replies to me seem to be reading in enormous amounts of bs that isn't in my remark at all. Patients being informed about their condition is not all about people promoting snake oil. For some conditions, the patients themselves are often better informed than general MDs. Only actual specialists in the condition really know more and going to a general MD with no experience in their specific condition sometimes has catastrophic (even deadly) results.
- inopinatus 9y ago
  You said everything of that sort. If that was not your intent, then perhaps in future you might say what you mean, rather than defending the vendors of false hope and perpetuating the extremely harmful myth that one can treat oneself. As in this: > patients themselves are often better informed than general MDs No, that is a gross overgeneralisation and not true of any condition. A few patients may have slightly better information in one dimension of their condition than a GP. Presuming otherwise is foolhardy arrogance that misses the profound interconnectedness and subtle complexity of body systems. And this is especially the case with endocrine and immune systems. Patients should be as informed as possible, yes, because this is always a benefit to one's treatment. Crossing the line into "I-know-better"-land is arrogance and idiocy.

tomhoward 9y ago

There seems to be a desire evident in the commentary on this topic to categorise CFS as either completely psychological, or completely physiological. My own experience, having had the condition for much of the past 10 years, and having (after many years of frustration) found treatment methods that have enabled me to achieve almost full recovery, is that it is very much both physiological and psychological, and that only by treating the mind and the body together can full recovery be achieved. Whilst many people will want to read this study as evidence that CFS is fundamentally physiological in nature, it doesn't do anything to dismiss the role of psychology as a causal or perpetuating factor. It is equivalent to using a lab test indicating (for example) imbalances of serotonin as evidence of depression, without taking into account the many years of stress and trauma that may have led up to the issue manifesting as a physiological (and debilitating psychological) condition. Whilst I have no doubt there is scope to develop treatments that can ease CFS sufferers' physiological symptoms, and I hope research findings like this can help to bring about these kinds of breakthroughs, I have no expectation that a comprehensive remedy for CFS can be found that doesn't include profound psychological healing as a key part of the treatment. It also occurs to me that a major reason why this condition continues to evade explanation and treatment by mainstream medicine, is that the profession is unaccustomed to looking at things as both psychological and physiological in nature, and that it will take a change in mindset on this to pave the way to discovering effective treatments for CFS and other such "mysterious" conditions.

cpncrunch 9y ago
My experience, having fully recovered, is similar, and it fits with what we know about how the brain works.
gerbilly 9y ago
What treatments did you discover?

Nightshaxx 9y ago

As someone who has suffered from CFS I am so happy to see it becoming more recognized and understood. You see, the frustrating part of having an illness like this is it is not well known enough for people to really understand it, but it has major impacts on your life. I can't tell you how utterly angring it is to be sitting in front of my computer and I know that if I just finish this school paper that isn't anything that hard, I can go to that social event, but I just am so tired I can't do it.

fcoury 9y ago
As someone whose symptoms fits the bill, how did you get diagnosed and how did you get it under control?
- GFischer 9y ago
  Be careful, those symptoms are also for a lot of other things including depression and burnout which are far more common amongst programmers. Do get diagnosed and get a second opinion, but it might or might not be CFS.

inieves 9y ago

CFS is most likely "Candidasis". An overgrowth of candida bacteria/yeast in the gut. This is very well known, and easily and cost effectively treatable. Consistent overconsumption of processed sugars leads to candida overgrowth. The body addresses this naturally through inflamation. Prolonged inflamation yields depression symptoms, and a host of other things. Google: candida You can recover from this mostly in one night for $5 and fully in about 2 weeks for $30. Ultimately these Stanford guys will try to design and patent an anti-inflammitory and it will cost you alot and not solve the problem. Address the source of inflammation. Im surprised no one in this thread knows this and debate has wandered into little to no value. If you are suffering from this, please please research candidasis or candida cleanse.

rfugger 9y ago
This study suggests that candida is probably not the culprit: https://www.ncbi.nlm.nih.gov/pubmed/18339054 https://www.ncbi.nlm.nih.gov/pubmed/18339054
Smaug123 9y ago
The trouble with this kind of comment is that I can find scores of people who say that CFS (and fibromyalgia) is most likely a misdiagnosed hypothyroidism, treatable with standard T3/T4. Lots of people say "it's obviously <this thing> treatable in <this cheap way>" for some value of <this thing>, and that makes them all less credible.
Kudos 9y ago
FWIW, this did not work for me.

visarga 9y ago

If you're feeling fatigued, try Calcium and Magnesium supplements. They're cheap and safe and you might simply have a lack of minerals that doesn't show up in blood tests. That's what it was for me anyway. From chronic fatigue to normal life - it feels like I took 15 years off. Calcium relieves muscle pains, Magnesium improves sleep and reduces stress. They can also have a laxative effect.

hellofunk 9y ago

I'm not sure if it's me or the article, but something about reading it just made me really tired. More so than, say, Javascript fatigue. Which is interesting, because usually that's my limit.

cpncrunch 9y ago

Here is why CFS research is so difficult: https://news.ycombinator.com/item?id=14896929 https://news.ycombinator.com/item?id=14896929

cpncrunch 9y ago

Some commentary on this study by experts: http://www.sciencemediacentre.org/expert-reaction-to-cytokines-for-chronic-fatigue-syndrome/ http://www.sciencemediacentre.org/expert-reaction-to-cytokin... In summary: - it's quite overhyped. - we already knew that TGF-B was elevated in patients. - as TGF-B wasn't increased after exercise, that puts into question how relevant it is as a biomarker, as symptoms tend to increase after exercise. - it doesn't give any indication as to whether the illness is organic or psychological, as both depression and lack of sleep cause inflammation.