
Scientists Edge Closer To Lab Test For Chronic Fatigue Syndrome - iamjeff
http://www.npr.org/sections/health-shots/2017/07/31/540565526/scientists-edge-closer-to-elusive-lab-test-for-chronic-fatigue-syndrome
======
kens
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
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
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?

~~~
Gibbon1
> how many things that we currently categorize as one disease are really many
> different diseases.

Had a GI doctor tell me he thinks there are 'lots' of gastrointestinal
syndromes that medicine has no way to identify. Also have read an
epidemiologist years ago that wrote there are probably a lot more infectious
diseases out there. Some of which may have serious long term complications.

~~~
tomkinstinch
Fortunately we have a tool to help on both fronts: metegenomic sequencing.
It's only just starting to be used in clinical settings in a non-retrospective
way, but many groups are interested in how the gut microbiome (or changes of)
can impact the etiology of GI disease. Several pharma startups are looking at
therapies for GI disease that rely on changing the gut microbiome, either
directly via introduction of new flora (fecal transplant or introduction of
tailored microbial cocktails), or via small molecules that can shape the
taxonomic distribution. Microbial cultures introduced to the GI tract tend to
either die off entirely, or become dominant. It's a bit of an unsolved puzzle
why the trend isn't toward plurality. The microbial therapies for _C. diff_.
are one example.

Beyond GI disease there's also indication that the gut microbiome has
psychological impact, and metabolic impact. There's a lot we don't know.

Metagenomic sequencing can disentangle the various organisms present in a
sample and report all of the taxa present, but the results are only as
good/complete as the database used, and unknowns can be a significant slice of
the pie.

When our group does deep-enough sequencing and _de novo_ viral genome
assembly, we often have enough contigs beyond our organism of interest to
assemble genomes for other viruses, and sometimes they are novel. Yes, there
are more infectious diseases out there.

A Chinese team exploring the viruses of invertebrates found nearly 1,500 new
viruses [1]. That one study expanded the list of known viruses by a
significant number, we're talking double-digit percentage change. Many more
viruses will be found, and some of them will be pathogenic.

In the (hopefully) near future it will be reasonable (if not yet cost
effective) to use tools like high-throughput sequencing to look at everything
in a sample, rather than ordering specific assays for individual pathogens.
It's a long road until sequencing will be part of the standard of care, but
we're in a golden age of biomedical exploration, enabled by sequencing and new
molecular methods.

1\.
[http://www.nature.com/nature/journal/v540/n7634/full/nature2...](http://www.nature.com/nature/journal/v540/n7634/full/nature20167.html)

------
propman
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

~~~
bogidon
> Rarely it is psychological

"Medically unexplained physical symptoms (MUPS) are physical symptoms for
which no relevant organic pathology can be found. MUPS are very common,
comprising up to half of all consultations in primary care and up to one third
of those in hospital outpatient clinics.1 Some studies indicate higher
prevalence; a landmark study of medical outpatients in North America with new
complaints of common symptoms such as chest pain, dyspnoea, dizziness, and
headache, found that an organic cause was demonstrated in only 16% of cases.

...Although MUPS are a major clinical problem and widely regarded as being
difficult to manage,4 sophisticated approaches to management or even
recognition of the problem are unusual, especially in hospital medicine." [1]

I do realize that a case being marked as MUPS is not _proven_ to be
psychosomatic (psychological). Yet if even a small amount of MUPS cases _are_
correctly diagnosed, there'd probably be enough of them to surpass the term
"rare".

Yes, ideally we would run every possible test on any patient that walks in
with a stomachache. But there are limits to our economy and to doctors' time.
It's a complex problem.

[1]
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2564157/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2564157/)

~~~
propman
The ailments you describe though can certainly be debilitating but require no
underlying diagnosis. Me and my mother have horrible migraines, no one knows
why but it doesn't matter because I was prescribed a medicine, didn't work. I
was prescribed a second one and it worked and it is frustrating and it sucks
but quality of life is the same.

For all those ailments, we can treat stomach aches, dizziness, headaches. But
when one day you're relatively healthy and 3 months later you can't walk then
you NEED a diagnosis. Its like when you get stomach aches vs stomach aches
plus throwing up for 99% of the food you eat or bleeding stools and frequent
constipation then you get a diagnosis to figure out what is going on, usually
a colonoscopy/MRI for IBS or UC.

For most things we don't need a proper diagnosis. A ligament tear grade 1,2,3
can be treated without any radiographs. Often similar conditions can be
treated with the same exact splint or therapy. There is no need to further
diagnose if quality of life can be the same with less than 6 months of
treatment and medications.

But when you can't work or do normal daily life functions al of a sudden, you
can't just give up and say too bad. Unfortunately if I had Medicaid that is
exactly what would have happened. Doctor classifies it under a broad diagnosis
requiring little tests and you're screwed for life. Since I had ppo from work,
I went to a bunch of doctors until I got a clear obvious diagnosis. Now that I
have a diagnosis I can improve.

Also, if problems aren't certain as they are chronic, widespread or hard to
diagnose you see certain specialists who are trained to diagnose. You don't
see a general physician

~~~
fao_
> Also, if problems aren't certain as they are chronic, widespread or hard to
> diagnose you see certain specialists who are trained to diagnose. You don't
> see a general physician

This is actually (imo) one of the largest failings in the UK's various health
systems -- Diagnosticians as you have them in the US, do not exist. The entire
system relies on GPs keeping up to date on various diseases and symptoms. This
means that a lot of the time diseases that typically present with vague
symptoms, like cancer, can go undiagnosed for years.

~~~
rifung
We have diagnosticians? This is my first time hearing of them so they must be
pretty rare.

~~~
turbulents
Would have been nice when one of my family members was in the hospital for 6
months. Maybe he was talking about Dr. House?

------
carbocation
The article is here:
[http://www.pnas.org/content/early/2017/07/25/1710519114.full...](http://www.pnas.org/content/early/2017/07/25/1710519114.full.pdf)

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.

~~~
jdietrich
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/depres...](http://www.mdedge.com/currentpsychiatry/article/76288/depression/depression-
and-inflammation-examining-link)

~~~
joools
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
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.

------
Mz
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)

------
tomhoward
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
My experience, having fully recovered, is similar, and it fits with what we
know about how the brain works.

------
Nightshaxx
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
As someone whose symptoms fits the bill, how did you get diagnosed and how did
you get it under control?

~~~
GFischer
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.

------
peteyPete
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
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.

------
cpncrunch
Some commentary on this study by experts:

[http://www.sciencemediacentre.org/expert-reaction-to-
cytokin...](http://www.sciencemediacentre.org/expert-reaction-to-cytokines-
for-chronic-fatigue-syndrome/)

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.

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

------
hellofunk
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.

------
visarga
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.

------
dawhizkid
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
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.

------
cpncrunch
Here is why CFS research is so difficult:

[https://news.ycombinator.com/item?id=14896929](https://news.ycombinator.com/item?id=14896929)

------
inopinatus
_" 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.

~~~
tomhoward
> "Do you know what they call 'alternative medicine' that's been proved to
> work? Medicine." \- Tim Minchin, Storm, 2008

I've been a big fan of Tim Minchin's, and thanks to living in one of the
cities where he built much of his early fame, I've seen and enjoyed much of
his work.

But I feel like a form of Godwin's Law should apply to this quote.

It's been done to death, it contributes nothing of value to the discussions in
which it is cited, it minimises and trivialises the horrible predicament of
people (like myself) who experience illnesses that mainstream medicine
can't/won't recognise or treat, and serves only to promote a sense of smugness
among people who think they have mainstream medical science on their side.

The point that people sharing this quote don't understand is this: For
mainstream medical science to 'prove' something to work, it requires huge
commercial and/or political incentives to do the research. If a pharmaceutical
company or research institution can't reasonably expect a study to result in
the development of a drug that can yield hundreds of millions or billions of
dollars, it doesn't get done. That leads to a vast gap between what has been
"proved to work" and what can actually work for people who take matters into
their own hands, as I've done very successfully.

It's notable that all the comments here seeking to refute Mz's comment are
doing so by exaggerating or outright misquoting what she said.

~~~
inopinatus
On the contrary, I shared this quote having full knowledge of the cost and
complexity and political barriers, having both studied the industry
academically and being personally close to medical practitioners engaged in
the research and implementation of new treatments.

I think all suggestion of "alternative remedies" is dangerous, since it opens
the door to those preying on desperation to sell false hope. I have an active
dislike of the phrase, because it fails to capture just how harmful they can
be, and how rarely they are actual remedies. "Unproven interventions" might be
a better name.

More precisely, they also serve to mask those treatments deserving of more
research that might actually have some potential, because such signal is lost
in the torrential noise of snake oil and quackery.

I join your criticism of the externalities in the US market-led system that
incentivise research into drugs of symptomatic relief rather than cures.

Nevertheless I believe that is a short-term systemic malfunction, and in any
event is not a severe problem elsewhere where drug pricing is regulated. Large
amounts of money and time are routinely allocated around the world for
fundamental research into many difficult and poorly understood conditions.
Pointing out that medicine can't treat everything is fine, because if it could
we wouldn't need more research. But claiming the research doesn't get done,
that's simply untrue.

~~~
tomhoward
_I think all suggestion of "alternative remedies" is dangerous, since it opens
the door to those preying on desperation to sell false hope._

I'm with you on practitioners who charge thousands of dollars offering to cure
terminal cancer with carrot juice and coffee enemas. But this is a very small
segment of the industry, and from what I've seen, anyone who does that for any
amount of time gets regulated or shamed out of business.

Most natural health practice is nothing of that sort. It's things like
diet/nutrition, exercise, stress/trauma therapy; all things that have
significant evidence of being beneficial.

All the treatments I've tried in my journey to get well fit into this
category: low-risk treatments for non-life-threatening conditions, that just
support the mind and body to heal and strengthen naturally over the long term.
I've been doing it for nearly 10 years and in that time my life has utterly
transformed.

Do you have any objection to this that doesn't rely on dismissing every health
provider without a medical degree as a dangerous charlatan?

~~~
inopinatus
Nutrition. Exercise. Stress management. I think these are mainstream health
practices.

There are practitioners with other qualifications. Although I've met physios
with some peculiar ideas that subsequently turned out to be have a very high
proportion of adverse effects (e.g. spinal adjustments).

My message is consistent, I hope: try what you will, but never pretend to
expertise, and steer clear of recommending or suggesting anything to anyone,
because at that moment one becomes a snake-oil peddler and are risking harm to
someone else. Recognise that even medical practitioners are taught not to
treat themselves or family because you cannot, _cannot_ be objective about it.

I do not express an opinion on your personal journey, except to say that
despite not knowing you from Adam it's still gladdening to learn that you are
feeling better.

~~~
Mz
_Nutrition. Exercise. Stress management. I think these are mainstream health
practices._

If you have a very serious medical condition, like cancer, and you talk to a
doctor about things like taking vitamins, most of them will pooh-pooh it as if
any impact it has is merely a placebo effect. Using nutrition, exercise and
stress management as part of your defense in the face of something that
doctors don't really know how to treat gets dismissed and attacked and
basically lumped in with snake oil. In fact, you are basically doing this
yourself with your wild misquotes of people here in service of some agenda
that has nothing whatsoever to do with trying to comprehend anything being
said here, as best I can tell.

~~~
inopinatus
I am not surprised that you dislike that I have rebutted your remarks.
Nevertheless, when I quote you, it is practically cut-and-paste.

Mz, I think your comments in particular in this thread have been worthy of
such strongly worded reprimand because they could lead others to attempt self-
treatment and to disregard medical advice.

The fact that you've done so by misrepresenting the character, motives,
competence and behaviour of practitioners is something I take further umbrage
at.

~~~
Mz
When you misquote me and then wildly twist my meaning, with zero intent
whatsoever to actually have any respect for me or understand anything I am
saying, yes, you very selectively cut and paste in order to try to make it say
whatever meaning you are attempting to force upon my words.

------
mudil
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.

~~~
dEnigma
How do you know this? Has the Russian government a public list of psychotropic
drugs it uses on its political prisoners?

~~~
mudil
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
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.

------
inieves
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.

~~~
Smaug123
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.

