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Oseltamivir (AKA Tamiflu)- To use or not to use?

by: LMWatBullRun

Mon Aug 24, 2009 at 13:21:31 PM EDT


There has been a recent push (putch?)  to limit the use of Tamiflu when treating the North American flu.  The assertion has been made that limiting indescriminant use of tamiflu will reduce the likelihood of Tamiflu resistance becoming a part of the dominant strains.

Does this make sense?  At first glance it does, but upon further reflection, I beleive that this would be a mistake.  Here is why-

LMWatBullRun :: Oseltamivir (AKA Tamiflu)- To use or not to use?
The unspoken assumption made by those promoting this policy is that Tamiflu resistance evolves in a patient treated with Tamiflu, or in other words, that when you get the flu and your physician prescribes Tamiflu, that in some cases the virus develops resistance, and this strain may be passed on to others.  In fact, this idea does not seem to agree with what actually happens:

First off, most transmission of flu occurs early in the cycle of infection, before the infected person shows symptoms, and before any Tamiflu is used.

Secondly, the evidence strongly suggests that flu strains 'trade genes' either by reassortment or recombination or both, in preference to individual mutation and evolution.

Thirdly, despite a relatively low level of Tamiflu use, Tamiflu resistant strains became dominant in seasonal flu in about 4 months time here in the USA last winter.

So, Tamiflu resistance is not primarily a result of overuse of Tamiflu, but an inevitable result of the existance of Tamiflu itself.

Another problem not addressed by those advocating restricting Tamiflu use is that there is no way to know who will get severe cases ahead of time.  Since Tamiflu must be administered within 48 hours of symptom onset to be effective, and since most severe cases turn severe only after several days of mild illness, once a severe case manifests itself it is too late to treat such a case with antiviral drugs.  People have died as a result of such mistaken thinking, and this will be a much bigger problem this fall.

Moreover, a recent study suggests that treatment with multiple different antiviral drugs, including amantadine, is synergistically more effective than the combined effects of individual antiviral drug treatment.  This is one case where the "shotgun approach" appears to carry a significant benefit.

My thinking is that in order to maximize effectiveness of the present stockpile of antiviral drugs that they should be prescribed liberally, in accordance with the judgement of the responsible medical practitioner, and emphatically not rationed.  If we ration antiviral drugs we will wind up with a useless stockpile of antiviral drugs and a lot of dead people who might have been saved.  

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bump n/t


KEEP THE GRID UP!
Prudent People Prepare Properly

"better to have it and not need it than need it and not have it!"


That makes sense to me, but who's in charge of that decision?
I wonder if there are "medium-risk" patients, with non-serious medical conditions that they just live with, during normal times, but that might tip the balance if they catch this flu.  Having a good relationship with your doctor could make the difference in getting the prescription.  Also bringing a list of your physical "quirks" might help your argument; you wouldn't want to rely only on the doctor's remembering your acute and/or chronic conditions and medications.

"The truth does not change according to our ability to stomach it."  Flannery O'Connor

there are a great many unknowns about this novel strain-
And one of the big unknowns is why some people get a serious case and others do not.  

I have seen speculation that the cause may be genetics, or unknown underlying health conditions, or obesity, or lack of vitamins, and others.

I do know that infectious bolus is one variable that has not been discussed (at least that I have seen) that has the potential to make a big difference in the clinical course, at least early on.  But I have no explanation why some people suddenly take a rapid turn for the worse.  Maybe bacterial pneumonia?

As regards the decision making process,  YMMV, but I am responsible for my health.  The doctor is "practicing" medicine, but for me there is no practicing-  it's for real, literally a life and death issue.  If the doctor does not agree with me on this particular issue, I'm getting another doctor.

If, that is, there are any doctors seeing patients at that point.  There may not be.......

The point of having this discussion now is to provide those of us who don't have access to a complete and well stocked pharmacopeia (i.e. almost all of us!) to have this discussion with their physician ahead of time.  I'd welcome The Doctor's input on this subject- paging Dr. Woodson!

KEEP THE GRID UP!
Prudent People Prepare Properly

"better to have it and not need it than need it and not have it!"


[ Parent ]
"Infectious bolus"?
Is that how much virus you're exposed to, like a little on your hand versus a sneeze right in your face?

"The truth does not change according to our ability to stomach it."  Flannery O'Connor

[ Parent ]
yup, thats it! N/t


KEEP THE GRID UP!
Prudent People Prepare Properly

"better to have it and not need it than need it and not have it!"


[ Parent ]
He's
probably basking in the sun somewhere, sipping on a Vitamin D3 martini.

[ Parent ]
I should have included:
;-)

[ Parent ]
antiviral 'rationing'
It depends on how big a stockpile your country has.  I've just been reading the PCAST report http://www.newfluwiki2.com/sho...  The US has a combined Federal and state stockpile of 90 million courses (80% tamiflu, 20% Relenza), with no expectation of being able to purchase more before the end of 2009.  The 'plausible scenario' presented suggests 60-120 million infections in the fall wave, with 45 - 90 million requiring medical care.  While on the surface it would look like there's enough for everyone who gets 'sick', there will be significant wastage and/or inability to access antivirals, with both under-treatment and over-treatment due to:

  1. under-diagnosis, ie failure to identify flu cases
  2. over-diagnosis ie other respiratory illnesses being ascribed to flu, eg RSV
  3. mis-match of distribution to demand
  4. mis-match of distribution between hospital vs outpatient use
  5. saving/hoarding antivirals for those deemed more 'at risk'
  6. saving/hoarding antivirals in case the pandemic becomes more severe
  7. giving higher doses and for longer, for those with more severe disease
  8. using antivirals for prophylaxis, eg for exposed individuals with severe underlying conditions.

Whether you believe some of the above is appropriate or not, these things are going to happen, especially the mismatch of distribution to demand - many things can go wrong at many points of that distribution chain.  

Which means that realistically, there WILL not be enough antivirals for for a 100% treatment-on-demand strategy (ie treat all suspected cases irrespective of severity).  



All 'safety concerns' are hypothetical.  If not, they'd be called side effects...


If - a really big 'If'
If they had only allowed individuals to purchase antivirals for personal use two years ago, or a year ago, or six months ago, a good portion of this problem could have been alleviated.  If everyone who realized it would be in their best interests to have a personal stockpile of antiviral drugs had been allowed to purchase the drugs, there would be enough drugs for those who needed them.

"If" . . . "if only " . . .

Too freakin' late, now.


[ Parent ]
not too late for the next one LOL n/t




All 'safety concerns' are hypothetical.  If not, they'd be called side effects...


[ Parent ]
Maybe . . .
But if the supply is so low that the US can't buy any more Tamiflu for the rest of the year, it's liable to be a good while before there's enough supply that individuals can buy it to stock up.  Maybe in time for the next one - but the way things look right now, maybe not.

Some fortunate ones of us were able to stockpile antivirals during the past few years - but not nearly enough of us were either able or willing to do so.

Things are crystal clear in hindsight - but the handwriting was on the wall on this one years in the past.  If this idiotic "nanny state" in which we lived weren't so determined to act as though people didn't have enough sense to have any control over their own medical care, we would have been allowed (no, not allowed - encouraged) to obtain our own antivirals for future use.

Far too many people are going to pay the piper on this one - and it would have been such a simple solution that it seems absolutely insane that this alternative wasn't available.  People are going to die because either their doc won't prescribe, or there won't be drugs available if they have a doc who will prescribe.

In my book, that ranks pretty close to killing people because it was decided that we didn't have the right to possess the medicine that could save our lives.


[ Parent ]
couldn't agree more
Amen, Clawdia

[ Parent ]
Oseltamivir - save for those with risk factors or who are hospitalized.
I truly wish I had time to respond in full, however there are a couple of things that I must address.

First for severe cases (i.e. sick enough to be hospitalized) starting Tamiflu after 48 hours does help see http://www.cdc.gov/h1n1flu/rec...

However, some studies of oseltamivir treatment of hospitalized patients with seasonal influenza have indicated benefit, including reductions in mortality or duration of hospitalization even for patients whose treatment was started more than 48 hours after illness onset.

The reason that it doesn't help most people if taken after 48 hours is that they don't need it.  These studies were done in healthy people and most healthy people  are already getting better at 48 hours so taking the drug doesn't change a thing.  Even if taken earlier the benefit is not that impressive, a shorter duration of illness by 1 1/3 to 1 1/2 day see http://www.tamiflu.com/hcp/inf...

Second, influenza mutates by drift and shift (trading genes).  Drift occurs in individual patients and are simply mistakes in viral RNA transcription.  We know know that it doesn't take that many mistakes in transcription to get tamiflu resistance in H1N1 (that may not be true for other strains).  Now if the person is already getting better with a strong immune system  and is staying home, it probably doesn't matter.  But if the resistance develops in someone taking it as prophylaxis or treatment and not staying home with good infection control at home then spread is possible (especially if their immune system is compromised).  And if someone is taking it for prophylaxis and not washing hands etc, by natural selection they will pick up and transmit resistant virus.

Third, as others mentioned there is not an unlimited supply.  It therefore makes sense that we save it for those at higher risk of complications (who hopefully will ALSO stay home and take steps not to spread resistant organisms) and for those who are sick enough to need to go to the hospital (and then with proper isolation.)   But if people just get their prescription and go about their business, you are likely to get transmission of resistant virus even if the contacts are not on anti-viral medication.  


unaccessible doctors
By the time patients in the U.S. are able to access their overloaded health care providers and are diagnosed and prescribed Tamiflu, the 48-hour window will have passed.

[ Parent ]
still, most people don't need it
the effects are modest and in children, it can with vomiting make dehydration worse.

Not easy to decide what the rigth thing to do is. Not obvious either direction.


[ Parent ]
I know that's what we're supposed to think -
But let's pretend we have two very Earth-like planets - so alike, in fact, that the only difference is that during an influenza pandemic caused by the swine variant of H1N1 flu, one planet has unlimited access to antiviral drugs Tamiflu and Relenza, and the other planet has no such medicines.

I can't help but believe that the planet with access to the drugs would, in the end, demonstrate significantly lower mortality and morbidity as a result of the virus.

It appears that you think otherwise.  But - if these medicines were of so little value as you seem to imply, then it seems one would think it to have been a waste of time and money to even develop them in the first place.  Personally, I can't help but think of foxes and sour grapes.

YMMV (obviously).



[ Parent ]
i see kids get better without the drug all the time
and i see kids get better with the drug. if they are sick I use,if not not. Every year.

Everyone seems so sure they know the answer. Not me. ;-P


[ Parent ]
nor me either ;-) n/t




All 'safety concerns' are hypothetical.  If not, they'd be called side effects...


[ Parent ]
I don't get
"that's what we're supposed to think".

Everything in life isn't a giant conspiracy to manipulate.


[ Parent ]
Everything isn't a giant conspiracy
Thank you for that statement, DemFromCT.   I never thought I was being unrealistic in thinking that very thing but I needed that reality check this morning.  

[ Parent ]
of course
caveat emptor ;-P

I see PH folks struggling with ths simply because answers aren't obvious, things change quickly, and institutions don't change quickly. They can do a much better job of explaining what they are thinking, methinks, but  I don't see it necessarily as intent to deceive as much as "I wish I knew".


[ Parent ]
EVERY medication has benefits and risks
EVERY medication has benefits and risk.  For those with risk factors for severe influenza illness and those who are hospitalized the benefit of taking the antiviral agent clearly out weighs the risk.  If we are talking about a government stock pile than the medication should go to those who need it most.  When supplies are abundant (and I have not heard of shortages in the commercial US market)  it does not make sense for most otherwise healthy people to take it after 48 hours because the benefit will be minimal at best and you will still get the side effects.  If you take it before 48 hours there is a benefit and I have no problem with anyone choosing to use it. (As long as you don't use it to hop out of bed and infect everyone with resistant organisms.) But since there are side effects and costs, I suspect enough people will choose not to use it that it will be accessible for both those who want it as well as those who need it most. For those in the US who are worried that they can't get it from their clinician then consider trying one of those urgent care centers set up in pharmacies. They are designed to move people quickly.

I like the story of the two planets but I want to add  a third planet where there was access to antivirals but they only used them where the benefit was the greatest and everyone washed hands and stayed home when sick.  That planet would probably have the LOWEST morbidity and mortality.  The planet where there were no anti-viral agents would be next because everyone was very careful about washing hands, keeping a distance where possible and following good infection control practices.  But on the planet with an unlimited supply, everyone was taking antivirals and a resistant strain developed and quickly spread since the folks weren't being careful. Lots of people un-necessarily suffered side effects since they took it in instances where there was no benefit.  And some high risk people died because the antiviral agent didn't work on their resitant influenza infection.  


[ Parent ]
I disagree, Dem
I think the obvious answer is to use what we have, as long as we have it, because eventually our Tamiflu stockpile will be useless anyway, and the timing of that event IS NOT dependent on Tamiflu usage.

Since the choice is going to be use it or lose it, I'd use it.

KEEP THE GRID UP!
Prudent People Prepare Properly

"better to have it and not need it than need it and not have it!"


[ Parent ]
heh
I think the obvious answer is save it for who needs it. :-0

[ Parent ]
who needs it?
Anybody with a clinical case of the flu NEEDS it.  There is no way to know which persons will develop a severe case!

KEEP THE GRID UP!
Prudent People Prepare Properly

"better to have it and not need it than need it and not have it!"


[ Parent ]
that's the dilemma
but most people don't need it. Give it to high risk (pregnant, <5 years, underlying condition.)

[ Parent ]
We Have Seen
otherwise health young adults and children with no underlying conditions. I wouldn't want to take the chance knowing it could be my child who just happens to be the "one". If you got it, use it.

[ Parent ]
difference in treating a population
and treating an individual. if the chance is, say, one in a thousand, and you want it, I can see where the doc would say no - and why the patient would say yes.

The problem is the data does not uniformly suggest great efficacy. The latest from UK suggest, for example, it won't help prevent asthma in an asthmatic, and cuts dfever by a day in most people. if it clearly worked better, different story.


[ Parent ]
my points were
1)That we are going to get resistant strains whether Tamiflu is widely used or not;

2) That early use prevents more severe case development;

New point-
3) How well do you think telling first responders not to use Tamiflu as a prophylactic measure is going to work, given the lack of PPE?

KEEP THE GRID UP!
Prudent People Prepare Properly

"better to have it and not need it than need it and not have it!"


[ Parent ]
The problem with health care worker prophy is how often
3) How well do you think telling first responders not to use Tamiflu as a prophylactic measure is going to work, given the lack of PPE?

Actually the problem with health care workers taking antiviral agents as prophy is trying to figure out if they have actually been exposed.  How many times do you take prophy? If you really weren't exposed you won't develop any immunity and you will continue to be vulnerable. Or do you take medicine all year and then get sick with a resistant virus three months from now.  Why not at least wait for the fever and then take treatment?  The treatment is over in 5 days and you are back to work 24 hours after your fever resolves. And you now have immunity. The other really big problem with health care workers taking it at prophy is what if they get a resistant organism but never get sick enough to stop working.  Do they then spread it to their vulnerable patients (and family members)?  

Also I have to ask what is meant by the lack of PPE? In the typical hospital setting the most important precautions are going to be droplet precautions and hand sanitation.I don't believe there are any current shortages. If we do get shortages, masks can be made from cotton, sterilized and reused.  And I don't think we will ever run out of good old fashioned hot water and soap.  


[ Parent ]
quick question
I'm sorry if this has been asked a million times, but ... if tamiflu is supposed to be given in the first 48 hours, what happens if it's given after that?  does it do anything? is there any benefit at all?

it's a relative, not absolute issue
Giving it within the first 48 hours is best, and the sooner the better, but in the case of severe illness or deterioration it's still worth giving it even after 48 hours.



All 'safety concerns' are hypothetical.  If not, they'd be called side effects...


[ Parent ]
using Tamiflu early
on non resistant strains virtually ensures survival.

How many deaths have there been of persons who started Tamiflu within 24 hours of symptom onset? I have heard of none.  Every death I looked at had one common factor-

Tamiflu was not administered, or was administered later than 48 hours of symptom onset.

With that in mind, what physician who takes the Oath seriously would not strive to prescribe antiviral drugs as soon as they reasonably could in a case of influenza?

Moreover, with the recent study about the synergistic effects of three antivirals, including amantadine, what well-informed physician would not use all three where possible?


KEEP THE GRID UP!
Prudent People Prepare Properly

"better to have it and not need it than need it and not have it!"


[ Parent ]
anecdotes are not data
data suggests (doesn't prove) otherwise.

Do antivirals work in children and adults?
BMJ 2009;339:b3172
Lancet doi:10.1016/S0140-6736(08)61345-8


[ Parent ]
here
BMJ:
Conclusions: Neuraminidase inhibitors provide a small benefit by shortening the duration of illness in children with seasonal influenza and reducing household transmission. They have little effect on asthma exacerbations or the use of antibiotics. Their effects on the incidence of serious complications, and on the current A/H1N1 influenza strain remain to be determined.

http://www.bmj.com/cgi/content...


[ Parent ]
lancet link no good
but see:

CONCLUSION: When it was prescribed at influenza diagnosis, oseltamivir was associated with reduced risks of influenza-related complications and hospitalizations for children and adolescents at high risk of influenza complications.

http://www.ncbi.nlm.nih.gov/pu...

for when to use and see also:

The relatively small reduction in symptom duration reported by Dr Shun-Shin and colleagues[1] in response to treatment with neuraminidase inhibitors was consistent with the results of a systemic review conducted by the Centre for Reviews and Dissemination, that assessed the effectiveness oseltamivir (tamiflu) and zanamivir (relenza) in healthy and at-risk adults,[2,3] and children,[3] presenting with symptoms of influenza. However, it is important to highlight the paucity of good quality data, particularly for children

http://www.bmj.com/cgi/eletter...

Point being, there's nothing open and shut about this.


[ Parent ]
Silly poem I made up
I once had a pig named Enza
Who was as big as a credenza
I fed him Tamiflu
And his resistence grew
So now he only gets Relenza

Cute, but...
..this isn't a substitute for our Friday joke thread is it?!

[ Parent ]
CDC says no Tamiflu for otherwise healthy people
If you are fortunate enough to have your own course of Tamiflu, I figure you should probably take it if you likely have the flu.  Otherwise, TPTB kind of make the decision for you.

I am home with a sick kid today.  My daughter has come down with something that is very flu-like.  Sore throat, aches and pains, tiredness, fever, slightly runny nose.  She informed me that there are kids at her school with swine flu (no word from the administration confirming that).  This is a small private school that she goes to.  Surely they could have let us know if they have confirmation that there are kids out with H1N1.  I took her to the doctor yesterday when she woke up feeling poorly.  They did a nasal swab and it was negative for flu (but the doctor said that she could still have it but it might have been too early in her infection).  I told the doctor that I wanted to bring her in early so if it is the flu we could get her started on antivirals.  The doctor said that per guidelines from the CDC they were not prescribing antivirals unless there is some medical condition that warranted it.


A 'doctor'
That prescribes based on bereaucratic edit instead of what his own judgement tells him isn't worth a bucket of putrefying spit.  A 'doctor' like that is not a doctor, not a physician, and you cannot trust him to do what is best for his patient.

And that IS the polite version of my thought on that matter.  Odds are that your child will be OK, and I hope that this turns out well,  but I will not have a doctor that won't follow his conscience and his Oath, bureaucracy be damned.

If it were me, I would ask that person whether he remembers the Oath he swore, and then ask him how he will live with himself if your child dies.

KEEP THE GRID UP!
Prudent People Prepare Properly

"better to have it and not need it than need it and not have it!"


[ Parent ]
that's a pretty useless thing to say to a doc
if they give it to you it's because they think it will help you. If they don't give it to you it's because they think it won't. It's that simple.

Your comment suggests that you do not accept the data that tamiflu is only middling effective, not a guaranteed preventative cure. You are fee to believe whatever you want, but the data suggests otherwise, hence the CDC recommendation. IOW, it isn't right because CDC says it, rather it seems like CDC is advising based on best available data, and docs will act accordingly.

What's called for is close contact with the doc until recovery so plans can change based on clinical course.


[ Parent ]
Dem, I do not agree.
CDC is NOT advising based on what is best for an individual patient.  They cannot.  The very idea is absurd.  There are over three hundred million individuals here in the USA.  How can a government agency individually determine what the best possible course of action might be for each of those people?  That is the function of a physician, acting independently according to his best judgement.

It might be argued that CDC is acting in the best interest of all of us, taken as a whole, but I would argue that, as well.  CDC is subject to the Iron Law of Bureaucracy, and what CDC is advising right now is what the bureaucrats in charge of CDC think is BEST FOR CDC and those who authorize their funding.

And no, I do not expect Tamiflu to be a panacea for the flu.  I DO expect that Tamiflu use increases the likelihood that an infected person will survive this infection.  I expect that use of Tamiflu, Relenza and Rimantadine all together will further improve the odds of survival.  That's what those who have treated severe cases of flu say works.  It may be scanty data, and you are free to dismiss that as anecdotal, but that is all the data we have.  The reason that this is all the data we have is in part because the Federal bureaucrats you appear to be defending failed to establish a robust testing capability, and refuse to publish the scant data they do have, data that would be helpful.  

I put far more weight on field experience from real doctors who take their Oath seriously than on the pronouncements of a bunch of bureaucrats.


KEEP THE GRID UP!
Prudent People Prepare Properly

"better to have it and not need it than need it and not have it!"


[ Parent ]
you're absolutely right that CDC is not advising oin individual patients
in fact, they shy away from giving too much advice to clinicians even when they should.  ;-P

It might be argued that CDC is acting in the best interest of all of us, taken as a whole, but I would argue that, as well.

Fair enough. I think they try, but are not above criticism. But my point is that as a doc, I'm not especially aggressive with tamiflu and not because of what CDC says but from looking at the same data. And I'm not spineless, although speaking of which, spine flu is pretty endemic.



[ Parent ]
I am NOT saying that every doctor should agree with me, Dem
 or that every doctor must prescribe Tamiflu for every flu patient.  That would be as bad as having every doctor do what the CDC says.

That's my point- A physician should be able to, and should, follow his conscience and his own judgment.

If you follow your judgment then you are free to do what seems best, and this tends to provide better outcomes.  Doing what a bureaucrat says will not provide a good outcome.  A really good doctor listens to that little voice inside when it speaks to him, and I think allowing the physician freedom of action is really important.

I don't want to get too focused on this, which is peripheral to the issue of whether it is helpful to restrict Tamiflu specifically.


KEEP THE GRID UP!
Prudent People Prepare Properly

"better to have it and not need it than need it and not have it!"


[ Parent ]
I'm good with that
and I agree... now you DID call the doc spineless... ;-P

[ Parent ]
oh, yes,
one other thing I'd say would be-

"Well, the guidance from the manufacturer is that Tamiflu is recommended for cases of influenza and is recommended by the manufacturer to commence within 24 to 48 hours.  Since it appears that my child has the flu, and since somewhere around 1% of the confirmed cases die of it, I think Tamiflu is indicated here.  And the FDA approved both the drug and the instructions for use, so 'doctor', if it's government approval you seek, I'd say you have all the approval you need."

Pause, then
"If you do not agree, please tell me, in writing, why you are denying my request for appropriate treatment."

If he's as spineless as it appears, that may help.

KEEP THE GRID UP!
Prudent People Prepare Properly

"better to have it and not need it than need it and not have it!"


[ Parent ]
can you keep the insults to a minimum?
things are going to be heated and there will be plenty of controversial decisions to discuss. Why don't we practice good behavior now so we get used to it?

And no, you are not being censored.


[ Parent ]
well said
I come on this site because by and large we seem to manage to avoid the mudslinging, name calling and general atmosphere of vitriol that is on some of the other sites..

[ Parent ]
I second that
Why don't we practice good behavior now so we get used to it?



All 'safety concerns' are hypothetical.  If not, they'd be called side effects...


[ Parent ]
Insults?
Who, exactly, am I insulting?

Passion, certainly.  I tend to get somewhat passionate when talking about the lethal effects of a lack of moral fiber.

Integrity matters.

Honor matters.

Honesty matters.

Courage matters, especially the courage to follow your own judgment.

These things matter especially when it comes to coping with unusual events, and still more when one's profession is advising others on such things.  Anyone who substitutes bereaucratic diktat for their own judgment has the effective intelligence of an invertebrate, as they have shortcircuited their own.    

One might argue that the physician in question was "just following orders" so to speak, but that argument won't cut it.  It might also be argued that the physician in question ought to be able to rely on the pronouncements of the CDC.  I disagree. Paraphrasing Owen Wister's words  "A doctor who hasn't any ideas of his own on flu treatment ought to be careful about where he borrows them." Borrowing ideas from government bureaucrats may be good for the CDC but bad for the health of the patient.

KEEP THE GRID UP!
Prudent People Prepare Properly

"better to have it and not need it than need it and not have it!"


[ Parent ]
you're a good man
see spineless cartoon elsewhere.

[ Parent ]
Daisy, you bring up some important points
1. confirmation of positive H1N1 is difficult. These days, the only confirmation is hospitalized and very ill people. it's not that they aren't telling you, it's that they don't know and won't know beyond suspected.

2. see comment above:

Conclusions: Neuraminidase inhibitors provide a small benefit by shortening the duration of illness in children with seasonal influenza and reducing household transmission. They have little effect on asthma exacerbations or the use of antibiotics. Their effects on the incidence of serious complications, and on the current A/H1N1 influenza strain remain to be determined.

tamiflu is not a slam dunk.


[ Parent ]
also home with sick kid today.... (waves at daisy)
My 11 year old started middle school 2 weeks ago, at a smallish suburban public school.  While they do have a hand sanitizer station at the entrance to the cafeteria, that appears to be the only step they have taken to reduce infection.  We received nothing from the school regarding any type of flu awareness until this Thursday...and it was the same old "cough or sneeze into your sleeve and wash your hands a lot" story we've been hearing elsewhere....no mention of H1N1 specifically. He reported Wednesday that had 1-2 kids in each class who were sneezing / coughing. I have friends who work in the local children's hospital and I've been staying in touch with them about trends....they are busy, but not crazy busy....yet.  The vast majority of the local cases have been extremely mild so far....some far less disruptive than a bad cold.

So, Thursday afternoon, my son is fine...allergy type symptoms only, common for all of us.  Thursday night, in an hours time, he becomes pale and has a temp of 102.7, chills, headache, sore throat, diarrhea, worse sneezing and mild cough. Friday I called his pediatrician's office, their policy is no appointments for "the flu" unless the parent wants TamiFlu...so we came in that afternoon.  His temp had been staying <100 and he was feeling pretty good with just a sore throat and nasal symptoms that day. Doc said he didn't like to treat kids with TamiFlu who didn't have other major health problems....due to possible side effects, cost to families, and reduction of duration of illness by usually only a day or so.  It was hard to disagree with him, looking at my son, who obviously felt pretty good. He instructed me to call him for TamiFlu if my son got markedly worse in the next 24 hours.  (oh, and they're not doing cultures unless the diagnosis is questionable somehow, or the child is acutely ill)

He did agree to giving ME TamiFlu for prophylaxis, (I work with high risk patients and also have a history of frequent bronchitis)  So I greatly appreciated the script.  He treated me like I had a brain, discussed my concerns with me, regarding my own use of Tamiflu...suggesting I go online and really read about the side effects (because they can include "some disturbing mental and emotional effects") before deciding to take it.  He gave me instructions for taking it either now, as prophalaxis, or later if I get symptoms.  

So, of course I've looked up the side effects.... WOW!  The reports of many individuals includes persistant effects long AFTER the course of TamiFlu has been completed.  A brief listing of the lasting effects reported includes disturbing dreams, debilitating dizziness, emotional instability, chronic diarrhea, numbness in fingertips, swelling of joints, insomnia, and mental fogginess or sense of unreality.  These were things that either caused people to stop using TamiFlu (makes me think some could be r/t the flu itself) or in many cases that continued to persist weeks and weeks after the flu and Tamiflu had been completed.  Granted, these are anecdotal, but we all have personal experiences and I think we can benefit from hearing about the experiences of others. Of course I realize there are probably many many others who have had nothing but positive experiences with this med.

So, for today, personally, my thoughts are, is it better for me to wade into the prophylactic TamiFlu experience now...knowing I may very well have another "known exposure" in a couple of weeks.  Or should I just wait until the first sign of actually getting the flu and take it then...knowing that the medical system here is still prepared and able to respond if I need it.  I'm really leaning towards waiting this out.   I can't help but think that having this now, especially if I can immediately bring on the TamiFlu (at the first ache or fever) would hopefully give me immunity, and therefore, some peace of mind for the future. I have zero signs of infection at this point and my son is nearing the 48 hour mark -- looking only like he has a mild cold.

thoughts?.......
and Daisy....please keep us updated on your daughter, I hope she has only a mild case and recovers quickly!!!


I'd say, hold the prophylaxis
Among other things, there's a risk of resistance developing, if you become infected and you are still taking the lower dose, before you are aware that you are infected.  The problem is not just getting a tamiflu resistant infection, cos your immune system may be able to clear it.  The bigger problem is passing it to your patients.

I'd say, take it if and when you become ill, and stay home till the full course is finished.



All 'safety concerns' are hypothetical.  If not, they'd be called side effects...


[ Parent ]
excellent thoughts Susan....good point!
I had just read how people on prophylaxis are really contributing to the resistant virus problem by going about their daily business while taking it.  I have known several people who seem to be of the mindset that the TamiFlu makes the virus they have been exposed to, weaker and unable to infect others.  I wish the docs would take the time to explain this to people before they put them on prophylaxis.  

Whether they're on TamiFlu or not, our hospital's policy is that if you have a family member with H1N1, you have to wear a surgical mask at work until you are 7 days from your initial exposure.  Ask me how many people are successful at wearing that mask 12-14 hours at a time....


[ Parent ]
Would anyone like to respond to these points?
First off, most transmission of flu occurs early in the cycle of infection, before the infected person shows symptoms, and before any Tamiflu is used.

Secondly, the evidence strongly suggests that flu strains 'trade genes' either by reassortment or recombination or both, in preference to individual mutation and evolution.

Thirdly, despite a relatively low level of Tamiflu use, Tamiflu resistant strains became dominant in seasonal flu in about 4 months time here in the USA last winter.  Right now, Tamiflu resistance in the North American flu (novel H1N1) is spreading, the best efforts of some to restrict it's use notwithstanding.

So, Tamiflu resistance is not primarily a result of overuse of Tamiflu, but an inevitable result of the existance of Tamiflu itself. Restricting use of Tamiflu will not prevent resistance from becoming widespread.

Another problem not addressed by those advocating restricting Tamiflu use is that there is no way to know who will get severe cases ahead of time.  Since Tamiflu must be administered within 48 hours of symptom onset to be effective, and since most severe cases turn severe only after several days of mild illness, once a severe case manifests itself it is too late to treat such a case with antiviral drugs.  People have died as a result of such mistaken thinking, and this will be a much bigger problem this fall.

A recent study states that most severe outcomes initially present with low/no fever; the case rapidly progresses to the point that Tamiflu is not effective and pulmonary function has been significantly degraded. At that point, absent heroic measures which will be unavailable later this fall if this pandemic really gets rolling, the patient is likely to die.

Moreover, another recent study suggests that treatment with multiple different antiviral drugs, including amantadine, is synergistically more effective than the combined effects of individual antiviral drug treatment.  This is one case where the "shotgun approach" appears to carry a significant benefit.

My thinking remains that in order to maximize effectiveness of the present stockpile of antiviral drugs that they should be prescribed liberally, in accordance with the judgement of the responsible medical practitioner, and emphatically not rationed.  

If we ration antiviral drugs we will wind up with a useless stockpile of antiviral drugs and a lot of dead people who might have been saved. And that is exactly what is happening right now.  People who presented atypically are very seriously ill or dead.

As regards the "tamiflu is not effective, so you don't need it" meme, that is hogwash.  While Tamiflu may not eliminate your illness, IT PREVENTS HEALTHY PEOPLE WHO TAKE IT EARLY FROM DYING.

Now, that comes with a price.  No drug I know of is perfect; all of them have potential side effects when used in clinically effective doses, and Tamiflu is no exception.  I'd rather deal with the side effects, if I have a clinical case of the flu, than run a 0.5% chance of dying.

KEEP THE GRID UP!
Prudent People Prepare Properly

"better to have it and not need it than need it and not have it!"


sure
First off, most transmission of flu occurs early in the cycle of infection, before the infected person shows symptoms, and before any Tamiflu is used.

actually the greatest infection period is in the first five days after symptoms appear, and in the first two days is the peak. Pre-symptom infection is oft cited and poorly documented. There's much we do not know about flu. But taking tamiflu doesn't stop you from shedding in that 48 hours of peak shed.

Secondly, the evidence strongly suggests that flu strains 'trade genes' either by reassortment or recombination or both, in preference to individual mutation and evolution.

Mostly reassortment, recombination as a major mechanism remains not only controversial but not well accepted by establishment types.

Thirdly, despite a relatively low level of Tamiflu use, Tamiflu resistant strains became dominant in seasonal flu in about 4 months time here in the USA last winter.  Right now, Tamiflu resistance in the North American flu (novel H1N1) is spreading, the best efforts of some to restrict it's use notwithstanding.

I think that's right. It does what it does, though that resistance may well have started in Europe or Japan where tamiflu is more commonly used.


[ Parent ]
can you please reference this?
While Tamiflu may not eliminate your illness, IT PREVENTS HEALTHY PEOPLE WHO TAKE IT EARLY FROM DYING.

is it your opinion or is it data? And if it is data, is it data on otherwise healthy peoplke, high risk, ICU patients, etc? Point being everyone agrees that sick people get it, high risk people get it, but my understanding of the data is that for your average joe who does not appear ill, IT PREVENTS HEALTHY PEOPLE WHO TAKE IT EARLY FROM DYING is not established (see my previous BMJ reference). If it were, it'd be a different story.


[ Parent ]
opinion or data?
This is my opinion, and it is not based on any published study.

My opinion was formed from my third hand review of fatal case information available online and in the media, and on the second hand information acquired from physicians who have treated H5N1 and H1N1 influenza cases.

The docs I have spoken with have all said that early treatment with multiple antiviral drugs provided the best chance of a good outcome.  The first I heard of this was at the May 2008 Panflu conference; I think you were in the room for that presentation, Dem.  That sparked my interest.  Since then, when I have had the chance, I have inquired about treatment regimen from those who have treated severe cases;  fortunately there have been few of those so far this year in my area, but that has limited my second hand data collection effort.  In those few cases locally, however, late administration of antivirals all correlated with severity.

In the third hand reviews, one of the things I noted over and over in the fatal cases was that people who died got antivirals late or not at all.  I found no mention of any person who died from this who got tamiflu or other antiviral drugs early (less than 48 hours from symptom onset).  Now, obviously, this is not conclusive, as the media reports may not include significant information, but my assumption has been that someone who started to feel bad on day X, and who did not go to the hospital until Day X+6 or X+3 or whatever,  did not get Tamiflu until after they had gone for treatment.  There may some who had their own Tamiflu but my assumption is that those cases are a vanishly small percentage.  I have not compiled a list of the fatal cases, as my time is limited, but I have looked at dozens of fatal cases and have yet to see one where antivirals were administered early.  If there are such, I'd be interested in looking at it. Anyone know of a fatility where Tamiflu was started early?

It would be very interesting to see a detailed study done on just this question, but the problem is that this pandemic will be well underway or maybe over before we see it.  It would even be interesting to see a comprehensive compilation of media reports, but although this could be more timely, it would not have the weight of a more formal study. So when coping with this situation we are back to opinion and hunches.

To summarize-  ALL severe cases appear to share late administration of anti-virals, but by no means are all those who get late or no anti-virals going to be severe cases.  There did not seem to be any way to determine who would get a severe case.  

With that in mind, and given that Tamiflu resistance appeared independent of Tamiflu use it appeared to me that aggressive early antiviral use was the better choice.  The recent report I read about severe cases starting with low/no fever appears to further support that view.

Absent any reason to the contrary, if/when my family members come down with this bug, I intend to press for early aggressive antiviral use.

KEEP THE GRID UP!
Prudent People Prepare Properly

"better to have it and not need it than need it and not have it!"


[ Parent ]
over 10 % of pediatric deaths took tamiflu within 48 hours
Our responses crossed however a recent study does show that
Among 31 children for whom antiviral treatment data were available, 19 (61%) received antiviral treatment, and four of those received treatment within 2 days of illness onset.

http://www.cdc.gov/mmwr/previe...

[ Parent ]
thanks for the information!
so 4 of 31 children got antivirals within the 48 hour window.  Does this article discuss which one?  I'd assume nobody would prescribe rimantadine.....but it would be good to know.

13% of children who died got antivirals early.  48% who got it late died, and 38% of those who died did not get antivirals.

In other words 87% of the pediatric deaths got antivirals late or not at all.  Does this article speak to co-morbidities?  

Are there data on adult infections?

I need to look into this and see what's there.  Thanks for the link!

KEEP THE GRID UP!
Prudent People Prepare Properly

"better to have it and not need it than need it and not have it!"


[ Parent ]
Interesting quote-
Antiviral treatment should be started as soon as possible after illness onset; evidence for benefits from antiviral treatment in studies of seasonal influenza is strongest when treatment is started within 48 hours of illness onset (5). However, treatment of any person with influenza who requires hospitalization is recommended, even if treatment is started >48 hours after illness onset.

KEEP THE GRID UP!
Prudent People Prepare Properly

"better to have it and not need it than need it and not have it!"


[ Parent ]
What is missing from this,
and what I would love to see, is a comparison of deaths in the early tamiflu start group versus pre-existing conditions.  

I would also love to see an analysis of adult cases.

KEEP THE GRID UP!
Prudent People Prepare Properly

"better to have it and not need it than need it and not have it!"


[ Parent ]
"Anyone know of a fatility where Tamiflu was started early? "
Yes, the boy who died of a SOD in Alaska on Friday, as reported in yesterday's news diary.

Hippocratic Oath: First, do no harm.


[ Parent ]
Seems to me
the acquirement of reistance to Tamiflu by influenza could largely be driven by the (large?) proportion of people who start a course but are unable to tolerate it. My daughter took 2 tablets and soon realised that vomiting followed.

See: http://www.dailymail.co.uk/hea...

If we knew that anti-virals were hugely beneficial (eg, either reduced symptom duration by 50% or, as you believe, prevented severe illness) then it might be possible to put up with five days of vomiting and bribe your children. But as neither of these is true, there is little inducement to finish the course and ensure the virus is destroyed.


[ Parent ]
Response to Points
First off, most transmission of flu occurs early in the cycle of infection, before the infected person shows symptoms, and before any Tamiflu is used. I believe some transmission occurs early but I have not found any evidence to document that belief.  I definitely do not believe that "most transmission" occurs before symptoms and in fact I "believe" most transmission is after symptoms start but before immunity kicks in. But I don't have articles at this time.

Secondly, the evidence strongly suggests that flu strains 'trade genes' either by reassortment or recombination or both, in preference to individual mutation and evolution.
Response - Influenza can only trade genes if the same host (human, swine, canine, bird etc) is infected with two different strains at the same time.  This is a very rare occurrence and is distinctly uncommon. (see http://www3.niaid.nih.gov/topi...  Drift on the other hand is far more common http://www3.niaid.nih.gov/topi... and occurs when errors are made as a virus replicates in a single host.  This H1N1 is probably just a couple of mutations away from tamiflu resistance.  Those strains will not necessarily be more fit than strains that don't have the mutation however if you have a lot tamiflu in use by natural selection http://en.wikipedia.org/wiki/N... the tamiflu resistant strains will be have an advantage over the tamiflu sensitive strains and spread.

Thirdly, despite a relatively low level of Tamiflu use, Tamiflu resistant strains became dominant in seasonal flu in about 4 months time here in the USA last winter.  
Response - Please keep in mind that last winter we had strains of H3N2 spread which were resistant to adamantadine class of antiviral medications and therefore CDC changed thier recommendations for long term care faculty to oseltamivir and zanamivir for prophylaxis.  Please see http://www.cdc.gov/flu/profess... for documentation. I already stated my opinion that prophylaxis is asking for trouble because individuals on prophylaxis continue their daily business and easily can spread resistant virus if they develop a subclinical infection to a resistant virus they are exposed to from someone else. Granted Japan which sees a lot of tamiflu use did not have much resistance develop in the country BUT the Japanese wear masks whenever they have coughs or colds http://boingboing.net/2009/02/... so they are wearing masks when they are on tamiflu.  Also tamiflu resistant strains were not dominant in seasonal flu last season, only tamiflu resistant SEASONAL H1N1.

Right now, Tamiflu resistance in the North American flu (novel H1N1) is spreading, the best efforts of some to restrict it's use notwithstanding.

Response - I do not believe this is correct.  I believe that we are seeing sporadic cases from drift but if these individuals stay isolated at home until after they are no longer sick they will not spread it.  I don't see evidence that this is not working.

Since Tamiflu must be administered within 48 hours of symptom onset to be effective, and since most severe cases turn severe only after several days of mild illness, once a severe case manifests itself it is too late to treat such a case with antiviral drugs.

Response - Actually Tamiflu should be administered within 48 hours because it provides no benefit in otherwise healthy people after 48 hours.  Their bodies are curing themselves.  It is like adding more water after the fire is already out.  The water makes no difference in the outcome and only causes water damage without any benefit.  But for people with ongoing infections, and/or  bacterial super infections it does make sense to use it after 48 hours.  Here is one study in a mice model -  http://www.h5n1-influenza.net/...

While Tamiflu may not eliminate your illness, IT PREVENTS HEALTHY PEOPLE WHO TAKE IT EARLY FROM DYING.

I don't believe this statement is true. You might be interested in knowing that

Duration of illness before death in the 36 cases ranged from 1 day to 28 days (median: 6 days). Among 31 children for whom antiviral treatment data were available, 19 (61%) received antiviral treatment, and four of those received treatment within 2 days of illness onset.
from http://www.cdc.gov/mmwr/previe...  If you look at the table you see that this includes one otherwise healthy child (who died with a staphlococcus co-infection) . So over 10 percent of pediatric deaths took tamiflu within 48 hours.  I don't know what percent of children with influenza took tamiflu but I suspect it is far less than 10 percent.  The bottom line is that I do not believe your statement is true and would appreciate documentation.

Please provide references to these statements so that I can respond.  I have not seen any evidence that they are true.
A recent study states that most severe outcomes initially present with low/no fever; the case rapidly progresses to the point that Tamiflu is not effective and pulmonary function has been significantly degraded.
..if I have a clinical case of the flu, than run a 0.5% chance of dying.

My point is simply that liberal use of tamiflu is not the answer to all problems related to influenza.  In addition, in the two countries that have used alot of tamiflu (Japan and Britian) concern has been expressed about side-effects -see  http://www.reuters.com/article... and http://www.bmj.com/cgi/content...  These concerns would NOT keep me from recommending  them for high risk individuals, but they have limited value at best for  healthy individuals. I have no problem with healthy people using it as long as they STAY HOME AND DON'T  SPREAD RESISTANT VIRUSES.  


[ Parent ]
That is not true
While Tamiflu may not eliminate your illness, IT PREVENTS HEALTHY PEOPLE WHO TAKE IT EARLY FROM DYING.

There is no morbidity data for antivirals. Certainly I have read lots of newspaper articles where the patient was treated with Tamiflu at onset but died anyway.

[ Parent ]
see, if you assume it's true
you really get angry. if you don't assume it's true, different story.

more data needed. But everyone agrees, if you are sick or high risk, you get it.


[ Parent ]
a precious commodity?
The debate - withhold or distribute Tamiflu - comes down to power and influence.

Those in power can write the prescriptions, if they so choose.  Those with money/influence could obtain the medicine through alternative sources, if they planned well ahead.  Developed countries may be able to benefit from this medicine while it's still effective.  

The biggest sufferers will be the less educated, the poor, and those in developing countries as a catastrophe unfolds.  


no question about developing countries
but you can't avoid an elitist system if only certain people can prescribe. The obligation is to do the right thing via evidence-based practice, and the question is what is the right thing?

UK does it different with tamiflu call-in lines, not without controversy:

It is the latest concern to emerge about Tamiflu, the powerful antiviral handed out by the Government to people with swine flu or flu-like symptoms.

Last week, Oxford scientists advised parents not to let children take it because the risks outweighed the benefits.

A recent study found Tamiflu caused side effects such as nausea and nightmares in children.

On Monday it emerged that ministers ignored a warning from their own advisors that handing out Tamiflu widely could do more harm than good, especially as most swine flu victims suffer only mild symptoms.

http://www.dailymail.co.uk/new...


[ Parent ]
btw, thanks to LMWatBullRun for a very enlightening
and lively discussion!

Lively you can just about always count on, Dem.
Enlightening?  Well, I hope so.

BTW, I agree that a partial course and/or circulating while taking prophylactic Tamiflu is a bad idea, especially for those around you. That was something I knew, but had not really considered as I should have done.  It's point worth hammering on, I think, and points up the need for PPE.

KEEP THE GRID UP!
Prudent People Prepare Properly

"better to have it and not need it than need it and not have it!"


[ Parent ]
Researching antivirals
Can't do better than start with the latest Cochrane Review
http://www.cochrane.org/review...

"Because of their [poor - Ed] performance, NI should not be used on their own, but alongside barrier (masks, gloves), personal hygiene and quarantine measures."


[ Parent ]
new guidelines
Treatment with oseltamivir or zanamivir is recommended for all persons with suspected or confirmed influenza requiring hospitalization.
Treatment with oseltamivir or zanamivir generally is recommended for persons with suspected or confirmed influenza who are at higher risk for complications (children younger than 5 years old, adults 65 years and older, pregnant women, persons with certain chronic medical or immunosuppressive conditions, and persons younger than 19 years of age who are receiving long-term aspirin therapy.
Persons who are not at higher risk for complications or do not have severe influenza requiring hospitalization generally do not require antiviral medications for treatment or prophylaxis. However, any suspected influenza patient presenting with warning symptoms (e.g., dyspnea) or signs (e.g., tachypnea, unexplained oxygen desaturation) for lower respiratory tract illness should promptly receive empiric antiviral therapy.
Clinical judgment is an important factor in antiviral treatment decisions for all patients presenting for medical care who have illnesses consistent with influenza.
Treatment should be initiated as early as possible because studies show that treatment initiated early (i.e., within 48 hours of illness onset) is more likely to provide benefit.

http://www.flu.gov/vaccine/ant...


tamiflu- to use or not to use
I  did not see any mention of the risk to the patient from taking Tamiflu in the previous posts.  There are always a few severe allergic reactions, as well as severe skin reactions that can end with death. Last year the labeling was ammended to include the risks  of neuro-psychiatric effects, including accidental death, especially in young children but also teens as well. This was based on FDA monitoring of adverse effects following a similar concern that surfaced in Japan in 2006, and led to governmental restrictions on the drug's use.

This complicates the calculation the patient and doctor make about using tamiflu either prophylactically, or therapeutically for early non-critical illness.

I doubt anyone has data to calculate the chances of injury from Tamiflu to weigh against the chances of injury from H1N1 infection. There will be plenty of estimates I am sure.

 It would not seem appropriate to suggest treatment to a healthy patient at low risk for severe illness, given that there is a risk of doing harm. Yes,there is a risk the patient may get sick, could possibly die, but if (s)he does fall ill there are still treatments to be given. If  you are a doctor, and the risks for your patient are equal, or aren't known, would you want to risk injury to your patient from giving medication, or from withholding
medication? Do you want your doctor to prescibe Tamiflu because you fear the H1N1 flu more than you fear Tamiflu?

As mentioned by others above, the doctor's creed is "Do no harm."  But people usually seem more likely  to be upset about receiviing too little treatment than too much. And lastly, just so you know these are real issues,  google "Tamiflu injury", and see all the ads for lawyers to take your case! They are taking Tamiflu very seriously!


Lawyers
There are always lawyers seeking employment - this is a litigious society.

In my case - yes, I'd much rather my MD prescribe Tamiflu than leave me with no recourse other than to take my chances with the virus.

This sounds like more scare tactics to me . . . I think you can safely believe that most of us here are aware of the risks of medication vs. no medication - we're not exactly naive about the risks.


[ Parent ]
The most detailed descriptions were on a lawyers' site.
http://injury-law.freeadvice.c...

Table 2 on page 3 has a chart of skin problems
http://docs.google.com/gview?a...

I had forgotten about that Stevens-Johnson skin syndrome.  Are there warning signs before the reaction gets too serious to treat at home?  It is really rare, though, isn't it?  

"The truth does not change according to our ability to stomach it."  Flannery O'Connor


[ Parent ]
it's really rare n/t




All 'safety concerns' are hypothetical.  If not, they'd be called side effects...


[ Parent ]
Tamiflu misperceptions
Sadly, in the coverage of this year's more severe outbreak, I still see the same mis-information being put forward by those who one would think would know better.

I remain as convinced as ever that early treatment with Tamiflu or Relenza is the proper course of action, especially with those more susceptable to the effects of influenza.

KEEP THE GRID UP!
Prudent People Prepare Properly

"better to have it and not need it than need it and not have it!"


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