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From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: misc.health.alternative
Subject: Re: surplus iron problem
Date: 9 Dec 1998 20:17:24 GMT
In <366E68CF.626F@zianet.com> "john s. flannery" <jflan@zianet.com>
writes:
>A close friend has developed excess iron in his system. Has to bleed a
>pint a week for the doctors. It is unusable for donations, unfortunately.
>
>I heard this was a problem in South Africa with Kafirs consuming large
>quantities of beer from earthen pots made from clay containing large
>wuanitities of iron. Found out about it doing a story on chelation with a
>university researcher, who unfortunately died several years ago.
>
>I am puzzled. Don't know cause or appropriate healing method. My father
>had a parallel situation where he produced large volumes of blood and was
>also tapped regularly. Don't know about him having excess Fe.
>
>Any ideas?
Cause in everybody but the iron overloaded beer drinkers, is
hemochromatosis, a simple genetic disposition to absorb too much iron.
Treatment is simple: bloodletting untl the body's iron is back in
balance.
The blood, incidentally, IS suitable for donation, medically. It's
being held up by ethical/political problems involving need for blood
donation to be voluntary, rather than "forced" as a needed disease
treatment (and one that is paid for by the donor, incidently). I think
this is stupid, but the powers that be disagree with me. Perhaps
policy will change. There is enough blood from treatment of this
disorder (which is perhaps the most common human genetic disorder) that
it would essentially solve the donated blood shortage.
Steve Harris, M.D.
From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med
Subject: Re: Donating Blood to thin and lower iron
Date: 1 Jan 1999 11:05:10 GMT
In <368cfe2c.297036467@news.erols.com> vl-hb001@erols.com (Terri)
writes:
Dr. Belknap
>>No such decision is necessary. Everybody pays. If you knew you would
>>live an extra six months of high quality life by donating monthly,
>>how much would you be willing to pay for the privlege?
Terri:
>Not one red cent. I would simply adjust my diet to lower my iron
>without phlebotomy. After all if we are teaching people to take better
>care of themselves and high iron is a danger to their health surely
>the medical profession is honorbound to encourage people to lower
>their iron levels by dietary and other non-invasive techniques where
>ever possible.
Comment:
Yes, but it's almost never possible. By the time you find out you
have hemochromatosis and organ damage you probably are a middle aged
man, or a post menopausal woman, and are overloaded by 20 grams (20,000
mg) of iron. Or more. Your body has no good mechanism to excrete
overloads (although there is a common myth that it has NONE. Actually,
people with 20 grams iron overload do excrete 4 times the iron per day
of normal people. But that's only 4 mg a day instead of 1 mg.)*
By constrast, it takes 80 pints of blood to remove 20 grams, at 250
mg each. On the other hand, you could go on a zero iron diet (if such
a thing existed) and remove it by the normal excretion of the 4 mg or
so you lose from skin cell sloughing, small intestinal blood loss, and
so on. That would take a minimum of 11 years, and since iron loss does
slow as body stores return toward normal, you can at least double that
time. Meanwhile, tissue damage continues.
If you are lucky enough to be a menstruating woman, you lose an
extra 4 mg a day on average, and thus it takes only 6 years to fix the
problem, rather than 11. But I think you're going to be in sad shape
by then.
Terri
> Or do you propose, along with the state taking
>possession of the bodies of the dead, that the medical profession be
>allowed to encourage unhealthy practices to force people into donating
>blood to maintain their health.
Comment:
No, we propose free education. Starting with you, and those
reading along. Novel concept, eh?
Steve Harris, M.D.
From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med
Subject: Re: Vitamin C and hemochromatosis
Date: 12 Jan 1999 07:38:20 GMT
In <36981EC2.436F@erols.com> "physical (Droll Troll)"
<physical@erols.com> writes:
> But, if blood tests are good for nothing else, they are good for iron
>status--but not for iron in tissue. People with access to regular blood
>tests may want to experiment with the the lowest intake of Fe that will
>keep their blood workup within normal, taking note of their C intake
>while doing this.
Depends on the blood test. The standard CBC won't tell you that
you're iron overloaded, but an iron/TIBC ratio will provide a pretty
good clue. And is not expensive. I think a good argument can be made
that it ought to be used as a screening test on the older population,
particularly men. Hemochromatosis is, after all, probably the most
common human genetic "defect." In my geriatrics population I suspect
about 1% of the folks are iron overloaded-- and that's remarkable, in
that a lot of the iron overloaded men have probably been selected out
by the time they get to the age where they're thinking about a
geriatrician, in one way or the other (they're dead or their primary
doc is a cardiologist)-- so I see far more elderly women.
From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med
Subject: Re: Elevated Alk Phos
Date: 24 Apr 1999 06:30:42 GMT
In <3720A1A3.87E1F0E7@Mindspring.com> Jim <JDBarron@Mindspring.com>
writes:
>In <36EB2F21.2A5089D@Mindspring.com> Jim <JDBarron@Mindspring.com>
>writes:
>>
>>Just a possibility: Elevation of Alk. Phos. is one of the earliest signs
>>of iron overload. If your serum ferritin is over 50% OR ( not "and" but
>>OR) your serum ferritin is over 150 you need further tests. US doctors
>>are grossly incompetent at diagnosis iron overload
>
>[...}
>
>> INFORM YOURSELF. You absolutely (if you live in the
>>US) CANNOT trust a doctor to do this correctly.
>
>
>
> Might I interject here that anybody who writes you to be wary of a
>"serum ferritin over 50%" has no business talking about the relative
>incompetence of physicians, U.S. or otherwise. How about the
>incompetence of advice you get from non-doctors on the net?
>
> Most people with elevated alkaline phosphataes do not have
>hemachromatosis. Think horses before zebras.
>
>=========
>Obviously I made a typo: It should have been "If your serum IRON is
>over 50% OR your serum ferritin is over 150, you need further
>tests.
It wasn't obvious, because I suspected that you didn't know what
you were talking about, and still don't. Serum iron is not measured in
%. That's iron binding capacity saturation (not the same thing).
>(I really am surprised that you did not recognize that as a typo - why
>would I have listed two different cutoffs for the same lab test?)
Do you really want me to list them?
>And while SOME non-doctor advice on the net IS wrong, much of it is
>BETTER and MORE ACCURATE that many doctor's. Why else would celiac
>disease be over 90% UNdiagnosed? And hemochromatosis over 90%
>UNdiagnosed? And on and on and on and on.
They go undiagnosed because they are (if you define the disease by
lab test) usually asymtomatic. And there is no agreement yet about
routine screening. In part, you can thank your lovely government for
this, having fined billions from companies recently which routinely did
26 channel chem panels on people as screens, which included iron tests.
These were replaced for a while by medicare with individual tests which
combined, cost more than the 26 channel tests in volume, if only a
couple of tests or more were done (which they usually needed to be).
Having been burned by this, Medicare authorized new panels of 4, 7, and
12 channel panel tests. But iron studies got left out, for cost
effectiveness reasons. Which means your government has made the
decision that it knows how much finding a case of hemochromatosis early
costs, how much not finding it early costs, and that money is saved by
the latter strategy. Write a letter to your congressman. I hope
you're not one of those people arguing that public insurance is a
wonderful idea, because medicare essentially is that. And you see what
kind of decisions such a giant "corporation" (which also runs jails and
prisons) gets to make. And enforce.
>I am a member of two support groups on the net and in BOTH groups the
>overwhelming majority of diagnoses were made because the PATIENTS
>informed themselves (after suffering from the gross incompetence and
>outright abuse of a number of doctors) and insisted that the appropriate
>tests were done and that they were referred to appropriate specialists
>(often have to get recommendation from the net as to WHO were COMPETENT
>doctors in that condition.
You'll get the same story in any group of people with a rare
disease (and symptomatic hemochromatosis IS rare. Just as symptomatic
coeliac disease is rare).
>A revolution is going on in medicine, a lot of it is taking place on
>the internet and most of the medical profession is blind to it (as
>they are to so much else). In no small part because they are so
>generally incapable of benefiting from criticism.
>JDBarron@Mindspring.com
Well, you know that medical libraries have hardly ever been closed
to the public. There is no internet revolution which physicians are
not just as much a part of as anybody (save, of course, net software
designers).
>PS Note that I did not try to imply that you were incompetent because
>of typos (which you made a number of).
Spelling errors and so forth? Those are spelling errors, not typos.
And a true typo is rather obviouss. Perhaps you meant brain cramp?
Mis-speak, but in print? These happen, but they're not so obvious.
One tries especially to avoid them in messages calling whole classes of
people incompetent.
>PPS "Think horses before zebras" is precisely why so many US
>physicians are so incompetent: If its not a "horse" they just ignore
>it.
"Think horses before zebras" means exactly what it says. Think them
BEFORE, not instead of. Again, hemochromatosis is far down the list
of the reasons for elevated alkaline phosphatase. Only if the commoner
reasons have been ruled out, should the less common ones be explored.
> "Zebras" are "too rare" to worry about! Trouble is that many
>"zebras" are NOT rare. Turns out that the ACTUAL incidence of celiac
>disease is TEN TIMES as high as has been claimed for decades.
Only if the "actual incidence" was redefined somehow.
> And the
>ACTUAL incidence of hemochromatosis is over TEN TIMES as high as
>claimed for decades.
Ditto. You're quite free to cite primary literature to back your
assertion up. In the meantime, sorry-- I don't believe it.
From: David Rind <drind@caregroup.harvard.edu>
Newsgroups: sci.med
Subject: Re: Hemochromatosis NOT a zebra! was: Elevated Alk Phos
Date: Mon, 03 May 1999 11:48:53 -0400
Jim wrote:
> > And there is no agreement yet about
> > routine screening.
>
> The studies have been done and published. LONG ago. The medical
> profession has just chosen to ignore them.
No, the medical profession has not chosen to ignore
them. There is real, valid disagreement about whether
and how to screen for hemachromatosis (just like there
is real, valid disagreement about screening for prostate
cancer).
Personally, I have started screening for hemachromatosis,
but it is not at all clear that: 1) this is beneficial,
2) that I have any clue how to screen. The problem with
how to screen is that if you screen with iron studies too
early in life you fail to detect the problem, if you screen
too late, the complications have already developed, and if
you screen too often, it is clearly not cost-effective compared
to other ways you could spend health dollars.
Don't take the simplistic view, "doctors are all a bunch
of idiots incapable of thinking sensibly about hemochromatosis."
The medical community is actually pretty smart, and when there
are major arguments about whether to do something like this,
there tend to be good reasons for disagreement.
--
David Rind
drind@caregroup.harvard.edu
From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med
Subject: Re: Hemochromatosis NOT a zebra! was: Elevated Alk Phos
Date: 3 May 1999 20:05:12 GMT
In <372D1C05.BF77FDA2@Mindspring.com> Jim <JDBarron@Mindspring.com>
writes:
>> Well, you know that medical libraries have hardly ever been closed
>> to the public.
>
>Really?! I wish you had told that to the medical librarians who escorted
>me out of several (because I was neither student nor doctor)!
I said "hardly ever", not never. Being open to the public is the
general rule.
>Wherever did you get THAT idea?
From being in perhaps 30 medical libraries in 6 or 7 states. I
don't think I've ever been in one closed to the public during all
hours, unless you count the dinky library of texts that some floors
maintain for students and staff. And perhaps the library at Orthopedic
Hosp in LA. Generally not the main library, if there is a library big
enough to be called one. Medical schools cannot close their libraries,
in part because they get too much public funding. Ditto for non-profit
insitution, which get too many taxbreaks on the basis of their
educational functions. A few private hospitals, particularly in bad
areas of large cities, may do so. Perhaps private medical schools
also-- I don't know. You certainly have many open ones in your area,
whereever you live. Tell me (in general) where that is (just the city
is fine), and I will demonstrate.
>I know how "think horses before zebras is MEANT to be used. BUt the ugly
>REALITY of how it is generally used is "just worry about the horses,
>forget about zebras, they are too rare to worry about" How else, pray
>tell, would you explain a doctor telling a patient that , yes, you DO
>have all the classic symptoms of ....., but it is TOO RARE so I will NOT
>test for it anyway. (I had that told to me for two conditions on a number
>of occasions (turned out I DID have both of them.) (The assholes just
>didn't want to be bothered with zebras. (Have to spend time to go look it
>up, etc. etc. More cost efficient to just write the patient off.) What
>would it take to get you to face up to a little REALITY Vs what you would
>LIKE to believe, Steve?
Well, there's hardly ever a good excuse for not doing a test which
you patient wants done. Though I've occasionally had a patient pay for
an off the wall blood test, since medicare won't, and insurance only
sometimes will.
And I do screen all patients for hemochromatosis myself. However,
it's hard to prove that this doesn't just waste money. The older your
patient the more likely they are to have problems, and many of mine are
medicare only. And medicare will not pay for most of these.
>> Only if the commoner
>> reasons have been ruled out, should the less common ones be explored.
>
>One more time Steve: hemochromatosis is NOT rare. GOT that! Everything
>you were taught in medical school is not true.
We were talking about the commoner reasons for elevated alkaline
phosphatase. Which is not present even in most people with iron
overload.
>> > "Zebras" are "too rare" to worry about! Trouble is that many
>> >"zebras" are NOT rare. Turns out that the ACTUAL incidence of celiac
>> >disease is TEN TIMES as high as has been claimed for decades.
>>
>> Only if the "actual incidence" was redefined somehow.
>>
>> > And the
>> >ACTUAL incidence of hemochromatosis is over TEN TIMES as high as
>> >claimed for decades.
>>
>> Ditto. You're quite free to cite primary literature to back your
>> assertion up. In the meantime, sorry-- I don't believe it.
>
>Is this the same Steve that always wants everyone else to do their own
>medline searches, why should he do it for them? But here it is anyway:
>
>NLM CIT. ID: 99043230
>TITLE: Prevalence of hereditary hemochromatosis in 16031 primary care
> patients.
>AUTHORS: Phatak PD; Sham RL; Raubertas RF; Dunnigan K
> O'Leary MT; Braggins C; Cappuccio JD
>
>..............
>
>The prevalence of clinically proven and biopsy-proven hemochromatosis
>combined was 4.5 per 1000 (95% CI, 3.3 to 5.8 per 1000) in the total
>sample and 5.4 per 1000 (CI, 4.0 to 7.1 per 1000) in white persons. The
>prevalence was higher in men than in women (ratio, 1.8:1). CONCLUSIONS:
>Hemochromatosis is relatively common among white persons. Routine
>screening of white persons for hemochromatosis should be considered by
>primary care physicians.
"Should be considered." Alas, not yet recommended as a public screen
by the major groups which consider such things. Not paid for by
Medicare and many insurance companies. Does the paper above consider
how much it costs to find a case with screening (at least $3000, and
probably logistically far more, since a blood test doesn't do it
alone), and whether that $3000 might save more lives (which will be far
less than 1, since not everyone with hemachromotosis that isn't
identified on screen is destined to die of it), if that money is used
for flu vaccine or pap smear clinics? What is the natural history of
the disease in people identified by screening, vs people from the same
group not identified, but known to have it? This is a tough ethical
problem, because ethicists will argue that you are obligated to treat
every person you identify with screening tests, but not ethically
obligated to test. However, to find out if a screening test is
ethical, it's necessary to find out if it does more good than harm (at
the very least), which is what we don't know for hemochomatosis without
a properly randomized study, where the disease is "screen-identified"
in some people without telling them they have it. One ethical way to do
this is screen for the disease in people from old stored serum, then
find them and do a followup. Stored serum studies are greatly
underappreciated kind of study in medicine. The Framingham study has
yielded vast numbers of insights already.
>NLM PUBMED CIT. ID:
> 9867748
>SOURCE: Ann Intern Med 1998 Dec 1;129(11):954-61
>
>Thats about one in 200. I would not consider THAT "rare".
No, but the number is of course in dispute. Your own next reference
disputes it- I don't even need to.
>TITLE: The significance of hemochromatosis gene mutations in the general
> population: implications for screening.
> AUTHORS: Burt MJ; George PM; Upton JD; Collett JA
> Frampton CM; Chapman TM; Walmsley TA; Chapman BA
>
>.....
>. CONCLUSIONS: HFE mutations are present in 38.4% of the population, affect
>serum iron indexes, and are important determinants of iron status. The
>population frequency of genetically defined haemochromatosis (C282Y
>homozygosity) is approximately one in 200 and is higher than the prevalence
>of clinically apparent haemochromatosis.
> NLM PUBMED CIT. ID:
> 9824612
>SOURCE: Gut 1998 Dec;43(6):830-6
>
>There's that 1 in 200 again!
Yes, it's one in 200 again. The only problem is that you're talking
about two different things. Wups.
>*1 Oops! I'm WAY ahead of the medical curve there! That information is
>only 10 to 15 years old.
Try for something newer, then.
From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med
Subject: Re: Hemochromatosis NOT a zebra! was: Elevated Alk Phos
Date: 3 May 1999 20:29:03 GMT
In <372DC565.70A6@caregroup.harvard.edu> David Rind
<drind@caregroup.harvard.edu> writes:
>Personally, I have started screening for hemachromatosis,
>but it is not at all clear that: 1) this is beneficial,
>2) that I have any clue how to screen. The problem with
>how to screen is that if you screen with iron studies too
>early in life you fail to detect the problem, if you screen
>too late, the complications have already developed, and if
>you screen too often, it is clearly not cost-effective compared
>to other ways you could spend health dollars.
Yep. It's easier for me, since I'm a geriatrician. I get flack
about it from the Family Medicine people, who of course see all ages
(iron deficiency anemia occurs in something like 3% of the population,
which is 3 times more than hemachromotosis even with liberal
definitions). I'm a geriatrician, and it's a better test for me,
though nobody knows how much better. Still, we live in a climate where
some people don't even look at a CBC before many surgeries. Fairly
large studies failed to show the money to do it was being spent wisely.
The question is not how much money a life is worth. Rather, in this
day and age, the question is: how much money do we have? What is the
maximal number of lives we can save with it? Or number of years of
life? And what do we do if these are different-- how make the
tradeoff? (A serious example of the last is the question of whether or
not age of the recipient should be considered for organs. Should the
20 year old get the kidney or heart ahead of the 70 or 85 year old? At
present we've decided "no." I would agree if years of life gained is
the same in both groups (which it might be for hearts in the 20 vs 70
year olds). But not the 85 year olds. And there is also the question
of quality of life, which is difficult to quantify, but not completely
subjective. Some people are miserable for reasons which have nothing
to do with organ failure, have been miserable before the organ failed,
and will be expected to be miserable after it is replaced. Should they
get an organ over someone who was happy and productive before they got
ill, and will be expected to be (are more likely to be) happy and
producting again when better?
From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med
Subject: Re: US Drs incompetent with Iron overload: WAS Hemochromatosis NOT a
zebra!
Date: 4 May 1999 06:57:22 GMT
In <372E5283.5C2C5EAC@Mindspring.com> Jim <JDBarron@Mindspring.com>
writes:
>There may be disagreement but it is based on ignorance and out of date
>information.
>
>Repeated studies have indicated that the TRUE incidence of
>hemochromatosis is around 1 in 200. This is a disorder that is
>1) inexpensive to screen for
False. It costs $1500 to $3000 to find a suspected case through
screening.
>2) easy to diagnose
But unfortunately expensive, for each of those cases found in
screening must be subjected to an expensive test (such as an MRI) at
$500 each. If your test is only 20% specific that adds another $2500
for each case identified for treatment.
>3) when diagnosed and treated EARLY, is 100% treatable (with NO
>disability and completely unaffected life expectancy)
Many late cases are also successfully treated. How many years of
life do you save with that $5000?
>4) the treatment is 100% safe and inexpensive
Close to 100% safe, probably. Inexpensive, hardly. Symptomatic cases
must be phlebotomized of 50 to 100 units of blood, and nobody does that
free (unless, of course, you lie like crazy to the Red Cross). It could
be done with low expense with a policy change, but that would require
some clear thinking by certain ethicists on the subject of blood
donation, which I been unable to get them to do. The obvious solution
is to phlebotomize anyone free, and then allow them the choice to have
that unit do into a person or not (which they mark on an anomyous card
with a unit code on it, exactly as is done now, just before donation).
Otherwise, as patient tracking improves and diagnosis improves, people
will be forced to pay for phlebotomy, which is expensive.
From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med
Subject: Re: Hemochromatosis NOT a zebra! was: Elevated Alk Phos
Date: 4 May 1999 13:01:52 GMT
In <372E63F5.CB0C2D24@Mindspring.com> Jim <JDBarron@Mindspring.com>
writes:
>> >What would it take to get you to face up to a little REALITY Vs
>>what you would LIKE to believe, Steve?
When you get specific.
>> >Is this the same Steve that always wants everyone else to do their own
>> >medline searches, why should he do it for them? But here it is
>> anyway:
>> >
>> >NLM CIT. ID: 99043230
>> >TITLE: Prevalence of hereditary hemochromatosis in 16031 primary care
>> > patients.
>> >AUTHORS: Phatak PD; Sham RL; Raubertas RF; Dunnigan K
>> > O'Leary MT; Braggins C; Cappuccio JD
>> >
>> >..............
>> >
>> >The prevalence of clinically proven and biopsy-proven hemochromatosis
>> >combined was 4.5 per 1000 (95% CI, 3.3 to 5.8 per 1000) in the total
>> >sample and 5.4 per 1000 (CI, 4.0 to 7.1 per 1000) in white persons.
>> >The prevalence was higher in men than in women (ratio, 1.8:1).
>> >CONCLUSIONS: Hemochromatosis is relatively common among white persons.
>> >Routine screening of white persons for hemochromatosis should be
>> >considered by primary care physicians.
>>
>> "Should be considered." Alas, not yet recommended as a public screen by
>> the major groups which consider such things. Not paid for by Medicare
>> and many insurance companies. Does the paper above consider how much it
>> costs to find a case with screening (at least $3000, and probably
>> logistically far more, since a blood test doesn't do it alone), and
>> whether that $3000 might save more lives (which will be far less than
>> 1, since not everyone with hemachromotosis that isn't identified on
>> screen is destined to die of it), if that money is used for flu vaccine
>> or pap smear clinics? What is the natural history of the disease in
>> people identified by screening, vs people from the same group not
>> identified, but known to have it?
Barron:
>The natural history is that
>1) people who are identified and treated early have NO effects from
>the disorder whatsoever.
I accept this.
>2) over 90% of those with the disorder (under current conditions =
>what it would be without screening) go undiagnosed and suffer the full
>effects: disability and early death.
You have no evidence to support that.
> The family histories of those who are
>diagnosed are USUALLY full of relatives who died early deaths with
>classic symptoms of the disorder.
I don't know what "full of" means to you. It certainly does not
necessarily mean a phenotypic penetrance of 90%, to me.
> And even AFTER they are diagnosed and attempts
>are made to get family members screened they STILL die needless deaths
>because THEIR doctors are do determined in their ignorance that they
>convince the relatives that they don't need to be tested. So we have
>to **WATCH** THEM DIE NEEDLESS PREVENTABLE DEATHS! How do you think
>THAT makes us feel? Do you wonder that we have a little anger that
>sometimes boils out?
I can see the anger. They lock you out of libraries. They
deliberately stick you with druggie smeared needles. They alter your
charts. They refuse you tests you requested. I have yet to see any
evidence of any of it. You could name the medical schools without
identifying yourself, but you don't.
> But it's not without benefits:
Let me guess: you're an attorney and you're suing them all.
Harris:
>> This is a tough ethical
>> problem, because ethicists will argue that you are obligated to treat
>> every person you identify with screening tests, but not ethically
>> obligated to test.
>
>Sounds like the old German ethics: "If I don't smell (or admit I do) the
>stench (from the ovens) I don't have any responsibility to wonder what
>it is."
Yup. Sounds like you're suing them all. I'll bet the "Nazification
of America" speech goes over really well.
> CURRENT information clearly indicates that screening IS >economically
>effective, by a WIDE margin.
No, in fact it does not. Here are a couple of abstracts for you,
rather more up to date. The CDC believes that key questions remain
unanswered in screening, and so does the French government (which
doesn't screen for this-- I know of no government program anywhere that
does). Questions such as natural course of the untreated disease,
penetrance, etc.
Ann Intern Med 1998 Dec 1;129(11):971-9
Iron overload, public health, and genetics: evaluating the evidence for
hemochromatosis screening.
Cogswell ME, McDonnell SM, Khoury MJ, Franks AL, Burke W, Brittenham G
Centers for Disease Control and Prevention, Atlanta, Georgia 30341,
USA. mec0@cdc.gov
Population screening for hemochromatosis done by using the transferrin
saturation test has been advocated by experts to permit the initiation
of therapeutic phlebotomy before the onset of clinical disease. The
discovery of a gene associated with hemochromatosis has made DNA
testing another option for screening and diagnosis. In this paper, U.S.
Preventive Services Task Force criteria are used to evaluate the
evidence for the usefulness of population screening done by using iron
measures or genetic testing. Published clinical research offers little
evidence to suggest that population screening for hemochromatosis done
by using genetic testing improves clinical outcomes. Although one
recently discovered mutation, C282Y, accounts for 60% to 92% of
cases of the disease in series of patients with hemochromatosis,
uncertainties remain about the clinical penetrance of various
genotypes; the accuracy of genetic testing; and the ethical, legal, and
social effects of genetic testing. Before population screening for
hemochromatosis done by using transferrin saturation testing can be
recommended, laboratory standardization needs to be addressed and
questions about risk for clinical disease in asymptomatic persons
with mutations or early biochemical expression of disease require
resolution. Evidence from case series suggests that hemochromatosis may
be associated with liver cancer, other liver disease, diabetes,
bradyarrhythmias, and arthritis. In all studies but one, however,
estimation of the magnitude and significance of this risk is limited by
lack of adequate comparison groups. The need for population data to
answer questions about penetrance among asymptomatic persons
should not impede efforts to increase the detection and treatment of
hemochromatosis in persons found to have elevated iron measures a
family history of hemochromatosis, or consistent early signs and
symptoms of the disease.
Publication Types:
Review
Review, tutorial
PMID: 9867750, UI: 99043232
----------
Rev Epidemiol Sante Publique 1997 Sep;45(4):315-27
[Should we screen for hemochromatosis? Critical analysis of the
literature].
[Article in French]
Charvet-Protat S, Yaouanq J, Fleurette F
ANDEM-159, Paris.
This paper focus on the main issues to evaluate before planning public
health interventions which may optimise the prevention of
hemochromatosis. The main indicators are considered: prevalence,
morbidity and mortality of the disease, efficacy of the available
treatment, sensitivity, specificity and predictive values of the
screening tests; potential benefit of a national screening
program in a public health perspective. These are evaluated through a
critical appraisal of the clinical, epidemiologic and economic
literature on hemochromatosis. The paper emphasizes how individual
behavior and preferences become crucial to take into account when
well-being subjects will face a population-based screening program. We
conclude that further arguments are required before the implementation
of a national screening program for hemochromatosis.
Publication Types:
Review
Review, tutorial
PMID: 9380912, UI: 98002229
----------
>
>> However, to find out if a screening test is
>> ethical, it's necessary to find out if it does more good than harm
>>(at the very least), which is what we don't know for
>>hemochomatosis without a properly randomized study,
>
>Read the literature, for crying out loud! There is abundant research
>indicating that screening is safe! Just how dangerous IS a blood
>test?
Not very safe when it leads to poking a hole in your liver. Or
even draining $600 from your pocket to get an MRI.
>> where the disease is "screen-identified"
>> in some people without telling them they have it.
>
>Obviously, while you may know something about screening in general you
>know NOTHING (at least nothing remotely current) about screening for
>hemochromatosis!
Gosh, just me and the CDC and the French and the Canadians and all
the rest of the world. Except maybe the hemochromatosis support
groups, which only know what they want. So typical.
>We already have MOUNTAINS of information on what happens if people are
>NOT treated.
Secret, unpublished data?
> There would be absolutely NO medical justification whatsoever for
>failing to notify those who tested positive in screenings for
>hemochromatosis (and for that reason they HAVE been notified AND
>TREATED in all screenings done.
No, they haven't. They've been notified only. A third refused
liver biopsy in the abstract you quote above (in the part you snip).
Another third of those "identified" in screening by repeated blood
tests were found not to have hemochromatosis (as defined by tissue
overload) at all. About the last third we can say little, except that
it's hardly fair to lump them in with the biopsy proven cases. They
are at least as likely or more likely to be iron overload free (since
prsumably the more ill they were or fatigued they were, the more likely
they would be to have the biopsy).
>It's time for the US medical profession to disentangle their ears from
>their anal sphincters and DO something.
Sez you, but you've yet to make a good argument. When you're
specific you're generally wrong. The rest of the time it's hard to
tell what you're arguing.
>You are talking about another 10 or 20 years (years to DECIDE to do the
>study, get the funding, then more years to DO it. Meanwhile, right now,
>well over 1,500,000 Americans have the disorder. And many of them will be
>disabled and many of them will die in the next decade if untreated.
Many of them? How many of them? The death rate in the entire
country is 2 million a year. If many of 1.5 million are going to die
in the next 10 years that would make the death rate -- what? 100,000 a
year? If a third are from liver cancer from the disease, that gives
33,000 deaths a year from liver cancer from this cause alone. Who's
missing them? They stain most of these at autopsy, so how do they miss
the iron?
>We have identified the gene.
A gene. Present in 60-92% of cases. Which means 8-40% lack it.
And none of which (fraction of disease with gene) implies anything
about what fraction of people with the gene get the disease.
> We KNOW that it affects iron regulation. We
>KNOW that iron will continue to accumulate INEVITABLY if the condition
>is not treated.
We know no such thing. Since iron loss increases with body load (a
little known fact) there may be people who stay at an elevated load
without ever reaching critical tissue amounts to do damage (they stay
at a high equilibrium). The age correlation for this disease, after
all, is very weak. In some studies it cannot be found at all. Does
that mean anything to you? After reading these abstracts, I may
actually have to _stop_ screening the elderly. They aren't as rich a
field as I thought to look. Relatives of known cases are better,
since they will be enriched in incidence of the gene by a factor of
7-15.
> We KNOW what the INEVITABLE effects of iron accumulation
>are.
Think you do.
>There really HAS to be a better means of population control than THIS,
>Steve!
I don't think that even if every one of those 1 in 200 people dies
a couple of years early, it quite counts as population control. Though
it would be a serious thing, if found.
>Has anyone ever done a STUDY on the use of tourniquets? I doubt it.
>Maybe we should stop using them and study them for 10 to 20 years?
>Should I notify all the EMTs?
No. But funny you mention bleeding (shock-trauma). Some can't be
controlled by a tournequette, and what do you do for that? For years
we gave fluids to bleeding patients in the field to keep blood pressure
up. All this did was make them bleed faster, in remote places where
there was no blood to give them. Lower pressures and thicker blood
made them slow down, and maintained pressure enough to keep the brain
alive. Finally somebody suggested studies of the "obvious" (or what
had been obvious) "fact" that plasma expanders were always good for
hemorrhagic shock in the field. Early results suggest that we should
have studied this years ago.
Never assume you know how a study will come out, if it's not
really, really obvious. There is that which is seen and that which is
unseen. If hemochromatosis screening for the general public didn't
have a cost, or had a low cost, it is obvious it should be done. Alas,
it has a high cost.
> 1) the Framingham study was necessary because of the complexity of
>contributing factors and mechanisms to CHD and our very limited
>understanding of it. This does NOT apply to hemochromatosis: we
>KNOW what the basic mechanism that causes the iron accumulation is.
>We KNOW the mechanisms by which the accumulation causes damage (maybe
>not ALL but we certainly know enough!
You don't know enough to predict who will get the disease and when.
Or even what statistical risk is, on the basis of genetics. I suggest
you do your Framingham and get back to us.
>DO you need to study starvation by withholding food from a study group
>for a few years to see what the effect is?
Nope. However, when it comes to lesser degrees of dietary
restriction, we badly need studies.
>> >NLM PUBMED CIT. ID:
>> > 9867748
>> >SOURCE: Ann Intern Med 1998 Dec 1;129(11):954-61
>> >
>> >Thats about one in 200. I would not consider THAT "rare".
>>
>> No, but the number is of course in dispute. Your own next reference
>> disputes it- I don't even need to.
>
>Um, did you bother to actually READ it Steve? It clearly says "1
>in 200".
> This number is OBVIOUSLY going to be higher than clinically
>apparent HH because it takes awhile for it to BECOME clinically
>apparent. The 1 in 200 is the number WITH THE GENES that WILL get
>the condition IF not treated. (The overload is NOT apparent at
>birth! So the total number of those with two mutations HAS to be
>higher than the number of those with clinically apparently HH even
>though ALL of them will >EVENTUALLY get clinically apparent HH. Get
>it?
No! You'll have to EXPLAIN it! When last I went to school, there
was one death for every birth on this planet. That means expansion in
population can lower death rate only temporarily, and during that time,
diseases which arrive late in life and cut life short are
OVERREPRESENTED in the dead, because they come from a later and larger
cohort (it's hard to have a disease which shortens life not causing a
greater age adjusted mortality).
Also, a disease that occurs late in life and invariably cuts life
short, would not be over-represented in autopsies, after birth rates
and death rates have stabilized for a century+ (or for max life span).
Or under-represented, since there is (again) one death for every birth.
Thus, for every baby with hemochromatosis, after a while there is a
death. If 1 in 200 have the condition and it kills them all, after 100
years of ZPG the death rate of people from the disease is the same as
the birth rate. That's the best you can do. Only a declining birth
rate and less than 100% pentrance (some people with the genes die of
other things) can under-represent the clinical disease in the dead.
Now, treatment can also cause underreprentation in the dead, but you
have to postulate a significant fraction treated. Which you don't.
Finally, you're arguing that the 1/3rd of high transferrins found
to have iron overload on biopsy, PLUS the 1/3rd which refused biopsy,
somehow should add up to the 1 in 200 who has two genes. The idea
being that the 1 of every 3 people who refuse biopsy do so because they
something to hide, I suppose.
Sorry, but different numbers.
>Um, how late at night WAS it when you were typing this, Steve?
Obviously not late enough to get what it is you're trying to say.
>And if you bothered to search there are HUNDREDS of articles on the
>incidence of HH! I'm sure that if there WAS **REAL** evidence
>contradicting that number you could find it.
There is no real controversy on the incidence of the gene or the
double gene. Controversy comes in saying what your incidence of
disease with 2 genes is, over time. And how well transferrin sats
predicting finding 2 genes. Or later symptoms and early death which
was preventable earlier, but not by the time of arrival of symptoms.
>> Yes, it's one in 200 again. The only problem is that you're talking
>> about two different things. Wups.
>
>Wups yourself! I am talking about EXACTLY the same thing: the number of
>people ***with two alleles*** for hemochromatosis. (In case you don't
>understand what THAT means, it means that 1) they DON"T have iron
>overload AT BIRTH (it takes awhile for the overload to accumulate
>remember?) and 2) that they WILL eventually get it IF they are not
>treated.
>
>Come on, Steve! Blow me away with some RELEVANT facts or references (but
>please, not any 30 years old!)
Here is a full abstract of one you cut. 2/3rds of people with high
transferrins were biopsied. Half of the people biopsied from having
high transferrins in 16,031 primary care patients, did NOT have tissue
iron overload. You decided that these will have, if they wait. The
authors add the ones who have iron overload and those who refused
biospy, and decided they had a group, which by some numerology you
decide is significant, because the same as the frequency of
homozygosity. But if transferrins were a good screen then all the
elevated transferrins would be homozygotes, and the number would be 50%
higher.
The reasonable thing to do is assume that the group not biopsied was as
likely or more likely to have no iron overload as the group which
allowed biopsy. Duh.
Prevalence of hereditary hemochromatosis in 16031 primary care
patients.
Phatak PD, Sham RL, Raubertas RF, Dunnigan K, O'Leary MT, Braggins C,
Cappuccio JD
Mary M. Gooley Hemophilia Center, Inc., Rochester General Hospital, and
the University of Rochester School of Medicine and Dentistry, New York
14621, USA.
BACKGROUND: Despite evidence from screening studies in northern
European populations, the prevalence of hemochromatosis in primary care
populations in the United States remains speculative. OBJECTIVE: To
establish the feasibility of screening for hemochromatosis and to
estimate the prevalence of hemochromatosis in a large primary care
population. DESIGN: Cross-sectional prevalence study. SETTING: 22
primary care practices in the Rochester, New York, area. PATIENTS:
16031 ambulatory patients without a previous diagnosis of
hemochromatosis. INTERVENTION: Serum transferrin saturation screening
tests were offered to all adult patients in participating primary care
practices. MEASUREMENTS: Patients with a serum transferrin saturation
of 45% or more on initial testing had a serum transferrin saturation
test done under fasting conditions and had serum ferritin levels
measured. Those who had a fasting serum transferrin saturation of 55%
or more and a serum ferritin level of 200 microg/L or more with no
other apparent cause were presumed to have hemochromatosis and were
offered liver biopsy to confirm the diagnosis. RESULTS: 25 patients had
biopsy-proven hemochromatosis; 22 patients met the clinical criteria
for hemochromatosis but declined liver biopsy and were classified as
having clinically proven hemochromatosis; and 23 patients had a
serum transferrin saturation of 55% or more with no identifiable cause,
indicating probable hemochromatosis. The prevalence of clinically
proven and biopsy-proven hemochromatosis combined was 4.5 per 1000 (95%
CI, 3.3 to 5.8 per 1000) in the total sample and 5.4 per 1000 (CI, 4.0
to 7.1 per 1000) in white persons. The prevalence was higher in men
than in women (ratio, 1.8:1). CONCLUSIONS: Hemochromatosis is
relatively common among white persons. Routine screening of white
persons for hemochromatosis should be considered by primary
care physicians.
PMID: 9867748, UI: 99043230
----------
> Fact is that there is NO good argument
>for NOT screening for hemochromatosis (and an argument based on
>outdated facts that are now proven to be false is NOT a good
>argument).
Hepatology 1997 Jan;25(1):162-6
The relationship between iron overload, clinical symptoms, and age in 410
patients with genetic hemochromatosis.
Adams PC, Deugnier Y, Moirand R, Brissot P
Department of Medicine, University of Western Ontario, London, Canada.
The aim of this study was to investigate the relationship between iron
overload, age, and clinical symptoms in genetic hemochromatosis. The
relationship was studied between clinical symptoms and liver iron
concentration, serum ferritin, and iron removed in a retrospective study
of 410 homozygotes diagnosed using strict criteria. No significant
relationship was found between liver iron concentration, iron removed by
venesection, and serum ferritin level with age. The prevalence of
cirrhosis, diabetes, cardiac disease, pigmentation, and fatigue increased
as liver iron concentration increased. The most common presentations at
diagnosis were fatigue or as an incidental finding in all age groups.
Twenty-seven percent of patients (110 of 410) had no clinical symptoms of
hemochromatosis. Iron accumulation is highly variable in patients with
genetic hemochromatosis. The significant relationship between liver iron
concentration and cirrhosis, diabetes, cardiac disease, pigmentation, and
fatigue confirms the importance of iron toxicity in the pathogenesis of
hepatic and extrahepatic disease. The nonspecific nature of the
presenting features in patients and the presence of significant clinical
symptoms in patients discovered through family investigations underscore
the importance of family and population screening for hemochromatosis.
PMID: 8985284, UI: 97138258
----------
From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med
Subject: Re: US Drs incompetent with Iron overload: WAS Hemochromatosis NOT a
Date: 6 May 1999 11:06:11 GMT
In <3730E7C4.42556CAA@Mindspring.com> Jim <JDBarron@Mindspring.com>
writes:
>> False. It costs $1500 to $3000 to find a suspected case through
>> screening.
>
>WRONG! (interestingly I note that you don't provide a reference. You,
>who are always demanding them!)
I can get an iron saturation test at a local lab as an add on for
$15. I doubt they come much cheaper. Multiply $15 by the 300-600
people you need to test to find a positive one.
> Even at that price it is VERY
>inexpensive. Remember that this is a condition that, in the
>overwhelming majority of patients, causes serious disability (often early
>in productive years), that requires very expensive medical care, and,
>ultimately early death (but not before many thousands of dollars of lost
>income, expensive medical care, etc.etc.etc.
Sorry, you have not yet provided a reference for this. The natural
history of this disease is not known.
>The total costs of all screening and diagnosis and treatment is many
>times less than the costs of NOT screening.
No reference. I have provided two articles which point out that
this calculation cannot be made without knowing the natural course of
the disease. What fraction of people with high iron saturations will
die early of hemochromatosis? What fraction of people with two genes
for the condition? Unknown.
>> But unfortunately expensive, for each of those cases found in
>> screening must be subjected to an expensive test (such as an MRI) at
>> $500 each.
>
>Again, WRONG.
>
>Those who test positive need further inexpensive screening tests.
>Many patients, on the results of these tests, will need only an
>inexpensive gene test and a course of phlebotomies.
An inexpensive gene test, eh? Where I come from that's an oxymoron
if ever there was one. How much did yours cost you (or cost somebody)?
> In younger patients and/or those without liver enlargement and with
>only mildly elevated liver enzymes and only mildly elevated ferritins,
> MRI is not needed
How would you know? Are you somehow under the impression that you
know what the natural history of such patients is? I suggest you write
a paper.
>(but even if it WAS in ALL cases this would STILL be very
>inexpensive since the initial screening has a LOW false positive rate
>if the correct cutoffs are used (this has also been established by scientific
>study. (And I have a list of articles and will get to the medical
>library in the next couple of days and post them here. BUt in the
>meanwhile some of your information is so seriously wrong that it needs
>to be challenged NOW.)
You have already posted a study which found that in a very large
population screen the incidence of iron overload was only 1 in 3 of
those found to have high iron saturations. 1 in 3 did NOT have it, and
1 in three refused biopsy. So it's certainly no more than 50% of
cases, and probably lower (since ill people tend to be more compliant
at suggestions for painful or invasive tests, the group of 1/3rd who
refused biopsy is likely to be less ill than the 2/3rds who did).
>
>> If your test is only 20% specific that adds another $2500
>> for each case identified for treatment.
>
>Quit GUESSING, OK? The specificity is somewhere in the upper 90's,
>depending on what cutoff you use.
No. For the cutoffs you suggested in screening, it is less than
50%. What the specificity (using biopsy as gold standard) is for
positive saturation test plus positive gene test, is not known.
> Obviously YOU have not read any
>articles on screening for HH. Want to state what YOU think the
>specificity is? (I'd advise you to actually check first.)
See above. The iron saturation test obviously isn't very specific.
The specificity of the genetic test cannot be known until the natural
course of the disease is known. As for the sensitivity of the genetic
test, again, I have already noted that only 60 to 92% of people with
iron overload thought to arrise from a genetic basis are homozygotes
for the most common gene, depending on the population. That's not very
sensitive. If you had a positive iron sat test, the gene test is
insufficiently sensitive for you to base any treament decision on a
negative one. (What do you do with a positive iron test who tests
negative for gene?) And if a test does not help determine your
treatment, why do it?
>And the BIG point that you missed it that this condition is GENETIC.
>That means that, by screening *relatives*, you can make it much more
>efficient.
Which is why screening relatives and screening the population are
two different questions. The first is recommended and standard
practise.
>> >3) when diagnosed and treated EARLY, is 100% treatable (with NO
>> >disability and completely unaffected life expectancy)
>>
>> Many late cases are also successfully treated. How many years of
>> life do you save with that $5000?
>
>Where do you get this (so called) "many"?
Many, as in "a substantial fraction of the total cases."
> And how do you define
>"successfully treated"? It has been VERY well established that many
>of the resulting problems are irreversible (liver damage,
>arthropathy, diabetes, and on and on and on.
Successfully treated means the person has no cirrhosis, and has no
symptoms. Mortality in this disease, after iron treatment, is almost
entirely due to hepatoma, and this occurs only to those with cirrhosis.
> (I hate to say this, but this
>is so at odds with the large body of literature I've read (and all of
>it very consistent) that I can't help but suspect that you are just
>pulling a guess out of your head.
Hardly. Harrison's Textbook of Internal Medicine notes that half
of *symtomatic* cases of the genetic problem (presumably all iron
overloaded) have no evidence of cirrhosis. One can infer that these
people can be sucessfully treated, at the very least.
> That would not be so bad if this was a discussion
>on some obscure topic. But PEOPLE ARE DYING, Steve. TOTALLY
>AVOIDABLE UNNECESSARY deaths.)
Your offer to donate to pay for free tests for everyone, is noted.
I doubt you have the money. Until you come up with it, this is a
public health issue, amenable to all the usual public health questions.
What does it take to find a case? How much money to save a life? Can
the money save more lives if used in another way?
>I have done a search and am going to the med library and will post
>references very soon. And then the people on this newsgroup will
>discover just how poor your grasp of your own limitations really is.
Don't hold your breath.
>The major limitation on the utility of one's knowledge is the
>knowledge of it's limitations.
Pot, kettle, black. How much are you suing for, BTW?
>> >4) the treatment is 100% safe and inexpensive
>>
>> Close to 100% safe, probably. Inexpensive, hardly. Symptomatic cases
>> must be phlebotomized of 50 to 100 units of blood, and nobody does that
>> free (unless, of course, you lie like crazy to the Red Cross).
>
>Firstly: the EARLIER you treat, the fewer the treatments that are
>required. Early cases may require only a dozen or even fewer. So
>screening SAVES a lot of money! What YOU are doing is to ignore any cost
>of NOT treating early (i.e.: the difference between the cost of treating
>early and the cost of treating late. Frankly, I would hate to see you in
>charge of calculating the cost/benefits of a screening.
One needs also to know the cost for treating people who never will
become ill. There is also a big assumption being made if one is
assuming that treating early and diagnosing early can more or less
prevent having to be treated again. We don't know to what extent
that's true. Giving up you Geritol and One a day with iron is one
thing. Missing your steak and eggs is someething else.
>Secondly: the treatments could be given for a small fraction of the
>current price (about a 10th) if they weren't used as a major profit
>maker by hospitals and the ARC, even if they WEREN'T used for blood
>products (as they are in most other countries!).
Any IV nurse can do a phlebotomy, if the unit is to be tossed. I
have even found home health agencies that will do it on bedbound
patients. I don't think you'll find it done by anyone on the cheap,
however. Too much time and money spent, and risk taken.
> And if we DO succeed in
>bringing the ARC around (even if it takes a class action lawsuit), of
>course it WILL be free in most cases.
Gee, I wonder who will be filing that lawsuit? My other comment is
that there's no such thing as a free lunch.
>Just how much longer do you think the public will put up with this? You
>can't hide it. The internet will get it out. More and more people are
>going to find out how many relatives suffered and died needlessly when
>the standards for diagnosis and treatment had already been established
>for DECADES.
>
>If I was in the medical profession I would want to start moving as fast
>as possible so I could get as much as possible done before people became
>too aware. Might lessen the eventual reaction a little.
>
>People are NOT dumb. They are quite capable of going back in the
>literature and seeing what was known and when it was known. Pleading
>ignorance is NOT going to work on THIS one, Steve.
>
>And in the coming weeks your wrong guesses and misinformation are going
>to be countered by many posted references.
Sez you. We're waiting.
From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med
Subject: Re: US Drs incompetent with Iron overload: WAS Hemochromatosis NOT a
Date: 7 May 1999 01:44:19 GMT
In <3731D3E1.DE5AC596@Mindspring.com> Jim <JDBarron@Mindspring.com>
writes:
>> >The major limitation on the utility of one's knowledge is the
>> >knowledge of it's limitations.
>>
>> Pot, kettle, black. How much are you suing for, BTW?
>>
>
>??? WHERE did THAT come from?
It came from Doc Harris' jaundiced and cynical view of human
nature. Just slipped out.
I notice you didn't deny it, though. It's enough to make one even
more jaundiced and cynical.
From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med
Subject: Re: US Drs incompetent with Iron overload: WAS Hemochromatosis NOT a
zebra!
Date: 7 May 1999 10:45:25 GMT
In <7gtcdb$vbv$1@nnrp1.deja.com> gnigh@agora.rdrop.com writes:
>
>In article <7gm5oi$33a@dfw-ixnews3.ix.netcom.com>,
> sbharris@ix.netcom.com(Steven B. Harris) wrote:
>> In <372E5283.5C2C5EAC@Mindspring.com> Jim <JDBarron@Mindspring.com>
>> writes:
>>
>
>> >Repeated studies have indicated that the TRUE incidence of
>> >hemochromatosis is around 1 in 200. This is a disorder that is
>> >1) inexpensive to screen for
>>
>> False. It costs $1500 to $3000 to find a suspected case through
>> screening.
>
>Dr. Harris is making up numbers. Genetic testing costs about $150. Serum
>testing costs about $20. Neither are 100% specific or sensitive, but they
>are quite ample for screening.
Can you multiply 400 by $20? I make it out to cost $8,000 using
YOUR made up numbers to test the 400 people to get the 2 people with
repeated high Fe sats (they are 1 in 200), only one of which will have
iron overload, and only one of which will have genetic homozygosity for
hemochromotosis. Alas while the 1 in each case is usually the same
person, there is discordance. Where the genetic positivity is not
predicted exactly by the iron sat test, what's the point in doing the
genetic test? If it's positive you say: Gee, that's interesting. I'll
treat. If it's negative you'll say: "Gee, that's interesting. I'll
treat." The utility of genetic testing is that it tell you whether
or not you need to screen relatives.
>Dr. Harris is calculating his numbers assuming
>that every individual screened is tested using genetic testing, which
>wouldn't happen.
No. Do your own multiplication.
> The much cheaper transferrin saturation test can be used for
>screening; genetic testing would only be employed on repeat "positive"
>saturation tests.
If you're prepared to phlebotomize to Fe deficiency on the basis of
just a positive transferrin test and gene test, and not phlebotomize Fe
sat positive people who are gene neg. If you geek, however, it dosn't
work.
>None of the screening tests are only 20% specific. HLA typing has a
>specificity in the 80-90% range.
Specificity is irrelevent unless you're doing a screening test, which
in this case you've point out it's too expensive to do. What you
really need is the positive and negative predictive power.
> The transferrin saturation test has a
>positive predictive value which varies widely depending on the tested
>population, but repeat testing and fasting can significantly increase
>the predictive value of the test. Usually this value is somewhere
>around %50. There is nothing unusual about repeat testing, as many
>tests require either repeat tests for verification or special
>stipulations for the tested individual (such as fasting).
Yes. So? You cannot improve your negative and positive predictive
values unless you use a test which has some measure of extra
specificity over the screen, on the population screened. If we get 10
people positive from the Fe/TIBC test we know that 5 don't have iron
overload on biopsy. But can we tell which are which by doing the
genetic test? If this doesn't allow you to rule anybody out for
further testing or treatment, then why do it? If the genetic test is
positive on most of these people (which I expect) then, again, why do
it? It won't save you much money on biopsy or MRI, anyway.
>The cost/benefit analysis has been spelled out quite thoroughly in the Annals
>of Internal Medicine at
>http://www.acponline.org/journals/annals/01dec98/ironover.htm,
>
>
>Greg Nigh
And refuted just as well by the CDC in the same issue. The article
you refer to is written by what is essentially a blood disease lobby
group. Of course they want money to study blood diseases. I suggest
they do a pilot project and show how much it costs to save a life this
way (if it can be done at all), in just the same way everybody else
has, from PSA screeners for prostate cancer, CXR screeners in smokers
for lung cancer, mammo screeners for breast cancer. All of these
sounded great on paper-- and only the last is panning out (and even
that's not certain). The problem was that we didn't know the natural
course of subclinically identified but UNTREAED disease, for any of
these problems. That's what led to radical mastectomies, radical
prostatectomies on people who didn't need them, and so on. And chest
X-raying smokers who have no change in symptoms, just costs money and
does very little good.
The rule is: if you're not sure, do a study.
>--
>Student, National College of Naturopathic Medicine
>(http://www.ncnm.edu), for whom I do not pretend to
>speak.
From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med
Subject: Re: US Drs incompetent with Iron overload: WAS Hemochromatosis NOT a
Date: 7 May 1999 14:26:40 GMT
In <3732D431.DB656ABE@cs.uoregon.edu> Bret Wood
<bretwood@cs.uoregon.edu> writes:
>"Steven B. Harris" wrote:
>>
>> In <3731D3E1.DE5AC596@Mindspring.com> Jim <JDBarron@Mindspring.com>
>> writes:
>>
>> >??? WHERE did THAT come from?
>>
>> It came from Doc Harris' jaundiced and cynical view of human
>> nature. Just slipped out.
>>
>> I notice you didn't deny it, though. It's enough to make one even
>> more jaundiced and cynical.
>
>Hmmm. You make an accusation against someone without supplying any
>evidence. They react with astonishment. You point out that they
>didn't deny it.
>
>Are you sure you aren't one of those scumbag lawyers you were talking
>about earlier? :)
When it's easier to deny it ("I'm not suing") than write "Where did
that come from?" it's a little funny.
And I do have evidence-- the problem is that it's not evidence you
can "see." This guy writes like a lawyer.
From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med
Subject: Re: US Drs incompetent with Iron overload: WAS Hemochromatosis NOT a
Date: 7 May 1999 22:43:35 GMT
In <373300F4.7FBD8F5@cs.uoregon.edu> Bret Wood
<bretwood@cs.uoregon.edu> writes:
>"Steven B. Harris" wrote:
>>
>> And I do have evidence-- the problem is that it's not evidence you
>> can "see."
>
>And while Richard tries to remind us that Doctors are human, Steve
>persists in trying to convince us that he is a God. :)
Nope. The the real problem with medicine: since everybody eats and
has a body they think they're automatic experts in nutrition and health
care. When the doctor suggests he or she knows more about the general
issues, he gets accused of trying to be God.
It's very odd. If a physicist tries to convince someone he knows
more about physics, he doesn't get accused of playing God. It's a
natural result of an education think you know more about the topics
you've studied than most people. There's no hubris about it.
Now I certainly realize that patients have expertise in their
particular bodies and how they work, that I don't. But even here there
is a tradeoff. Many times a patient has come to me thinking A caused B
for them, and I have pointed out that in most people it's C that causes
B, and had them say "I never thought of that. Maybe it's that way for
me, too, because I've been doing C." And had them try stopping C and
find that it was indeed the culprit. If there's one nearly universal
experience of doctors, it's that patients are generally not as
different from the crowd as they think they are. I can't count the
number of people who've said to me "You know, I react just totally
opposite to drugs than the way I'm supposed to." If this was really
true of all the people who'd said it to me, the "normal" way the drug
was supposed to act would be opposite as well <g>. And strange to
tell, most of those idiosyncratic reactions disappear in unconcious
patients, so they don't worry the anaesthesiologist when he's alone
with the patient's physiology, and doesn't have to worry about the
patient's psychology. Idiosyncratic reactions happen, to be sure. But
there's a huge anxiety component to them. Getting rid of them is one
reason why shamaistic practices are so useful in medical care. It can
either be orthodox shamanism (the white coat magic) or religious
shamanism (blessings) or something wild (ceremonial magic, secret herbs
or piercings) from the alternative medical world. Anything to convince
people that they aren't been treated as a cog or a widget, and that
they have some special and personal saving grace going for them, which
as a talisman will ward off of the statistical evil. I've felt need
for this in my own medical care, so even knowing about it and feeling
rational, does not obviate the need for some form of it. I personally
job and take vitamins. But everybody needs SOMETHING.
From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med
Subject: Re: US Drs incompetent with Iron overload: WAS Hemochromatosis NOT a
Date: 8 May 1999 09:21:39 GMT
In <3733BD07.83246152@cs.uoregon.edu> Bret Wood
<bretwood@cs.uoregon.edu> writes:
>And BTW, this "evidence" was about law, not medicine. But then you
>Gods (or prophets, whatever) aren't really limited by the arbitrary
>disciplinary boundaries created by mortal men.
I see he's gone out of town without making a reply. Aren't you
going to look silly if he is an attorney? You'll have to call me lucky
or call me Zeus.
From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med
Subject: Re: Gregory demonstrates that Medical denial is a reality!
Date: 10 May 1999 06:34:50 GMT
In <3735D1C8.8AEC7FF7@Mindspring.com> Jim <JDBarron@Mindspring.com>
writes:
>> Mr. Barron (esq?), I notice, has still not answered as to whether or
>> not he's a lawyer, in the process of suing. Interesting, eh? I'm
>> going to nominate him for #2.
>>
>>
>
>I hadn't bothered to address that question because it looked like so much
>of the badmouthing you do I didn't realize that you really wanted an
>answer.
>
>Not that you DESERVE one, but no, I am not a lawyer (although I have had
>to represent myself several times in court - and won every time. What you
>have to do in the US when you don't have a lot of $$$.
>
>And, no I have never sued anyone (except an employer for back wages -
>which I won.)
Thank you. I take it you're not suing anyone NOW, right? English
doesn't have a natural past perfect. You mean, for the sake of the
record, that you have not filed or have pending, any suits but the one
you describe?
From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med
Subject: Re: Gregory demonstrates that Medical denial is a reality!
Date: 11 May 1999 14:26:14 GMT
In <3737963A.C41729F6@Mindspring.com> Jim <JDBarron@Mindspring.com>
writes:
> Nothing that I have said has ever
>indicated that I was planning to sue. And you seem singularly incapable
>of accepting that I am not. I even LISTED the reasons why I could not!
>Most reasonable people could get from that that I was not now either. But
>just to satisfy YOU, no. That's N. O. (negative). Get it?
Yep. Good for you. My apologies for misjudging you.
From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med
Subject: Re: QT3???
Date: 23 May 1999 22:12:32 GMT
In <3748580B.2ED73EC@cs.uoregon.edu> Bret Wood
<bretwood@cs.uoregon.edu> writes:
>Doctors frequently miss certain types of diagnosis for years.
Hypothyroidism isn't one of them. Hemochromatosis presenting as
nothing but arthritis and fatigue may be. If fact, generally you find
the average missed hemochromatosis patient has had so many thyroid
tests it's a wonder the blood loss hasn't treated the real problem by
serendipity.
From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med,sci.med.radiology
Subject: Re: CT scan worries
Date: 25 May 1999 01:34:03 GMT
In <374991B6.30C3DE24@Mindspring.com> Jim <JDBarron@Mindspring.com>
writes:
>"Steven B. Harris" wrote:
>
>> In <37488013.250D6C70@Mindspring.com> Jim <JDBarron@Mindspring.com>
>> writes:
>>
>> >> You're not espousing any earth-shattering truths here, Jim.. Any
>> >> internist would check a Hct, MCV, Ferritin, iron, and TIBC if
>> >> working-up a new-onset hepatitis with negative infectious
>> >> etiologies... "DUH."
>> >
>> >Um I was talking about Hereditary Hemochromatosis, or didn't you read the
>> >entire post?
>>
>> So was he, or didn't you feel you read his post? Do "ferritin,
>> iron, and TIBC" mean anything to you? Hint: iron and
>> T otal I ron B inding C apacity are use to calculation iron saturation.
>
>I would like to reply to whatever point you seem to be trying to make, if
>indeed, there IS one.
>
>But you have snipped so much that I have no idea what the heck you are
>going on about!
The above exchange is quite enough. He said any good internist
would check those things, and you said you were talking about
hemochromatosis. What did you say that, when the tests he mentions are
hemochromatosis screens?
>And I a VERY familiar with ferritin, iron, TIBC and the calculation
>of iron saturation.
>
>Here's one I bet YOU didn't know:
Here's one you don't know yourself, alas.
>Many (probably most) laboratories INCORRECTLY report all iron
>saturations of OVER 100% as merely "100%" (check out the forms
>and see!)
There is nothing incorrect about this. You cannot have iron
binding capacity saturated over 100%, for the same reason you cannot
have a cup of liquid which is more than 100% full. This is a matter of
definition, not physics, so it's on the order of the fact that you
cannot have more or less than 3 feet in a yard. When something is
reported as % of full saturation, the number cannot be greater than
100, since this would be physically meaningless.
You can have more iron in the blood than it takes to saturate the
iron binding capacity, the the saturation remains 100%. Just as you
can have more oxygen in the blood than it takes to saturate 100% of the
hemoglobin, and that doesn't change the fact that the hemoglobin
saturation is still 100%.
>The correct calculation is, of course
>Iron saturation = [(serum iron/ TIBC) X 100] (Well DUH! hardly
>rocket science!)
It's also incorrect, so I suppose this is rocket science to you.
This calculation is correct for all ratios of total serum iron to TIBC
(total iron binding capacity) up to 1.0. Above 1.0, the saturation is
100% by definition.
>So if your serum iron is HIGHER than your TIBC then your iron saturation
>has to be GREATER than 100%, right?
No, for the equation then becomes invalid. Saturation cannot be
greater than 100%, since you cannot have be more saturated than fully
saturated. Again, by definition, for when we say fully saturated we
mean no more iron binding is possible.
>But that's not the way most labs report it. Apparently because of a
>misconception that "you can't get more saturated than 100%"
>(technically true)
No, Jim. This is true. Technically true, definitionally true.
Which is to say, true (that's shorthand, you know).
> and therefore the amount OVER 100% is not significant (VERY VERY
>FALSE).
The idea tha Fe/TIBC > 1.0 is not considered significant is your
straw man. Reporting the saturation as 100% when it is in fact 100%
makes no judgement, expressed or implied, about the significance of a
Fe/TIBC greater than 1.0. If you want to know the Fe/TIBC ratio, the
lab supplies the numbers so that you can work it out yourself. Don't
ask them do the ratio and then multiply this interesting number by 100,
however, and call it something it isn't.
>The amount OVER 100% is FREE and UNBOUND, meaning that it freely
>causes direct toxicity effects as well as being freely available to
>pathogens (which is the reason that Vibrio fulnificus, a trivial
>infections for healthy adults, is so dangerous to those with iron
>overload that they are "lucky to even make it to the hospital alive"
>(as stated in one report)). So the amount in excess of 100% is the
>most important of all.
Unbound iron is simply TIBC minus Fe, and there's no need to bring
ratios or percents into it. And if you want to know that number, you
can do the subtraction. You seem quite confused about this, but labs
and doctors are not. Thanks.
>But since the misleading way that labs report iron saturations in excess
>of 100% obscures the excess, the significance of this excess is not
>likely to be appreciated.
Labs report nothing in a misleading way. They report the truth. If
it looks misleading to you, that's because you're pushing a
misinterpretation. That's your problem, not mine.
>Keep grasping Steve. Maybe you'll actually grab a straw someday!
You've got enough for both of us. Enough straw to build a really
large man out of it, to vent at.
From: sbharris@ix.netcom.com (Steve Harris sbharris@ROMAN9.netcom.com)
Newsgroups: sci.med.cardiology,sci.med.diseases.hepatitis,sci.med
Subject: Re: Please Help with Diagnosis
Date: 5 Aug 2004 15:56:37 -0700
Message-ID: <79cf0a8.0408051456.31c91dd8@posting.google.com>
"Dr. Andrew B. Chung, MD/PhD" <andrew@heartmdphd.com> wrote in message
news:<411223E4.2AAF@heartmdphd.com>...
> Darren Weston wrote:
> >
> > Profile:
> > 28 y/o
> > male
> > obese
> >
> > Problem:
> > I have been going through various symptoms of for months. Started with
> > cold, gradually got alot worse to the point of light headedness with
> > sharp chest pains either side of my left breast. also sometimes
> > tenderness all along bottom of rib cage, and intense gurgling down
> > left side of chest wall, like air passing through but very loud! no
> > curshing feelings on chest. no arm pain at this point. no out of
> > breathe. gradually got better. light headedness no longer present, but
> > occassional chest pain still there. also now, i seem to have developed
> > a lump feeling at base of throat, occasional quick moderate shooting
> > pain along underside of forearm, moderately tense/tight feeling across
> > top of shoulders and very top of chest, slight tenderness to right
> > jugular area of neck, occasional pain between shoulder blades slightly
> > left of centre and to a lesser degree at the front of chest.
> > throughout this i have also had a tender spleen (not 100% it is spleen
> > but it is in upper left quandrant of abdomen).
> >
> > had echocardiogram - clear
> > ecg's - 95% clear, tho one did show abnormal Tbar
> > blood pressure avg 140/90
> > high ALT enzymes - 150
> > moderate gamma gt - 50.1 (doc not worried by this - said up to 50 is
> > limit)
> > high iron levels
> > other blood profile attributes normal.
> >
> > has anyone got any ideas what this could be?
COMMENT from Dr. Chung:
> Could be hematochromatosis.
COMMENT from Dr. Harris:
LOL! Could be anything. Is this one of your "observations", Dr. Chung?
I think your divine inspiration is letting you down here.
There's nothing in the symptoms above to make any competent doctor
think more than half a second about hemochromatosis. Not that a 27
year-old man is likely to have symptoms even if he did have the
disease. And any symptoms he had from the disease would not likely be
any of these. People with hemochromatosis generally have severe liver
and hormonal and skin problems before they get heart failure.
Hemochromatosis cardiac symptoms are those secondary to heart failure,
which dosen't sound like anything here. This guy complains of pain.
And anybody with cardiac symptomatic hemochromatosis would not likely
have a normal echo, which this man has.
So far as the labwork, there really isn't anything to make one think
of hemochromatosis either. A mildly elevated ALT is nonspecific and is
frequently seen in the obese and the diabetic. Without a high AST to
go with it, it certainly isn't an iron-poisoned liver. "High iron"
levels in a routine SMAC-20 are neither sensitive nor specific for
anything. They really mean very little without a TIBC and a ferritin.
My personal beef with the labs that have started adding serum irons to
their screening chem panels, is that they NEVER do reflex iron
saturation and ferritins for high irons, and thereby cause a lot of
consternation and repeated blood draws, in a lot of people, for
nothing. Since most of these turn out to BE nothing. All they are good
for, is worrying doctors who should know better. And who *would* know
better if they had any clinical experience.
Chung, I recommend a little less time with your bible and a little
more with your textbook of internal medicine.
SBH
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