Effect Measure

One of the most feared outcomes of infection with influenza is Acute Respiratory Distress Syndrome (ARDS; in less severe form it mahy be called Acute Lung Injury, ALI). For reasons we still do not understand, cells deep in the lung that are involved in gas exchange (oxygen and carbon dioxide) become so damaged that the basic work of supplying the body with enough oxygen for life and getting rid of the carbon dioxide generated by metabolism is too much for the patient and either some intervention to relieve the lungs of some of the work is made or the patient dies. ARDS is so severe that often no intervention works, and fatality ratios of 50% are quite typical. The most common intervention is a mechanical device called a ventilator to do some of the work of breathing for the patient. Critical care respiratory therapy is much more than pumping air in and out of the lungs, however. It is a very complex and tricky art, and it is now believed by many that conventional mechanical ventilation can make ARDS worse and decrease the odds of survival. The literature on ventilation in ARDS is highly technical, and advanced methods using sophisticated computer-controlled devices are often needed.

Both the devices and the expertise to use them in ARDS are in short supply and will be a significant bottleneck if the flu pandemic is severe this fall. Even trying to figure out how serious the situation might be is fraught with difficulty, as a recent paper in PLoS Currents/Influenza demonstrates. It was an attempt to figure out how much stress will be put on Intensive Care Unit capacity given reasonable assumptions about how swine flu might evolve. The method used to make the estimate is easy to understand because it is is so simplistic, but even so, illustrates the difficulties.

The short paper, more of a back-of-the-envelope calculation, was done by researchers from a consulting group and hospitals in California and Washington DC (Swine origin influenza A (H1N1) virus and ICU capacity in the US: Are we prepared?, Zilberberg et al., PLoS Currents/Influenza). Here’s what they did. They start with the population of the United States, which they give as 307,024,641 (NB: all their estimates are expressed with the same degree of meaningless excess of significant figures, so I am going to round their numbers for clarity; for example, in this case I’d just will say 300 million). They then assume that the attack rate (per cent of the population infected) will be 15%, but allow it might be as low as 6% or as high as 24%. Thus they are acknowledging uncertainty around the 15% number, which they will use in a way I’ll describe shortly. These figures were taken from numbers given at a CDC press briefing on August 24, so they represent CDC’s estimates at that time of the pandemic. Once flu season starts in earnest, attack rates of 30% may be more likely, but for this paper 15% was used. That attack rate represents about 46 million flu cases, but with the uncertainty included, they come up with numbers between 37 and 55 million. You can think of this as a confidence interval around the 46 million point estimate. How did they get these numbers?

They used something called a Monte Carlo simulation and it works like this. The 46 million number is easy to see. It’s 15% of 300 some odd million. If you were using an Excel spreadsheet (which is what they used), you would enter the US population in one cell, the attack rate in another cell and then have a formula that multiplied the two together in a third cell. The problem with this is that while the population of the US is a fairly stable number, the 15% attack rate is a guess. There might be quite a lot of plausible attack rates, of which you judge that 15% is the most likely but many others possible. Think of a bell-shaped curve with 15% in the middle and many values higher and many lower. This bell curve can be very spread out or very sharp and peaked, depending on how sure you were about the 15%. What the authors did is construct a bell curve that used the two other figures expressing the uncertainty (the 6% and the 24%) in terms of its spread. Imagine, now, a gigantic pile of tokens with attack rates written on them (many will have 15% written on them, somewhat fewer that say 14% or 16%, and even fewer that a percent or two of numbers that are less than 6% or higher than 24%). Now instead of putting 15% into your spreadsheet cell, you reach into this gigantic pile of tokens and pull one out and put its value in the cell instead. Maybe it’s 19% or 11% or 15% (since there are more 15% tokens than anything else, but depending on the spread of the bell, there still may not be that many). Now let the spreadsheet calculate the number of cases (the token-drevied attack rate times the population). That will give you a number of infected cases. Now put the token back in the pile and do it again. And again. And again. The authors did just that ten thousand times, although of course they used a computer and an add-on to Excel called Crystal Ball which allows you to stipulate various kinds of statistical distributions for your token pile. Theirs was bell shaped, as described. When you do this you get another bell shaped curve representing the range of infectives, complete with the peak value (the center of the distribution) and the 95% confidence interval (in this case the part of the bell with 95% of the stuff under it).

Now you can do the same thing for the rest of the calculation. Let’s go back to the single calculation. You’ve got the number of infected cases in the cell with the formula (population times attack rate) and you multiply that by the proportion of cases you expect to be hospitalized. They used data from California for swine flu H1N1 which was estimated at that point to be 6% with a low of 2% (assumed) and a high of 10% (from the early Mexico data). Some of those hospitalized will be so sick that they wind up in the ICU on ventilators (12% from Mexican data, low and high guesses of 6% and 18%), and of those, again using Mexican data, 58% end fatally (low and high guesses of 40 and 60%). Now they do the random selection in each of these cells simultaneously 10,000 times, and that’s how the joint confidence intervals are figured. Here are the results (rounded estimates and 95% confidence intervals):

  • US pop: 300 million
  • Cases: 46 million (37 – 55 million)
  • Hospitlizations: 2.8 million (2 – 3.6 million)
  • On ventilators: 132,000 (228,000 – 454,000)
  • Deaths: 192,000 (126,000 – 226,000)

This corresponds to an overall case fatality ratio (CFR) of out 0.5%, comparable to the early estimates from Mexico. Since some of the most important data is from those early weeks, this isn’t surprising. But since there has been a lot of questioning of the applicability and accuracy of the Mexican CFR to the US setting. In a paper published in Eurosurveillance, a group from New Zealand used numbers from later in the pandemic and a variety of different CFR estimation methods and came up with dramatically lower numbers (0.06% to 0.0004%). Using a 30% infection rate (twice what the ICU paper used) still resulted in dramatically lower numbers for deaths. Instead of the roughly 400,000 deaths the US would expect under the ICU paper assumption (taking account of a 30% infection rate), the estimates from the Eurosurveillance paper would run from 3600 deaths to 54,000 deaths (there were no ventilator estimates).

Thus we have point estimates for the US that go from 3600 to 400,000 deaths, with some in between. The 3600 deaths estimate (a CFR of 0.0004%) seems wildly low, given that swine flu seems much like seasonal flu in virulence. Even the 0.06% figure (54,000 deaths) seems low, given the usual seasonal flu estimate is 0.1%. But in every case where assumptions have been made, they seem plausible, even if markedly divergent. Unfortunately the differences are of great significance. The ICU figures may be too high because of the use of Mexican estimates that were biased upward, but they only used a 15% attack rate which is likely too low. And the cases will not be coming into hospitals uniformly but in huge clumps or bunches. No hospital has a reserve of expensive mechanical ventilation equipment.

One can easily see that the scenario depicted by Helen Branswell in her piece, “War against H1N1 likely to be fought in intensive care units” is likely right on target. Given the numbers, it’s hard to see how we can win that war.

Comments

  1. #1 Dylan
    September 9, 2009

    (I emailed this to a friend, yesterday. It was in response — a second response; the first was not nearly so polite — to an idiotic statement (with regard to novel H1N1) sent to him from some gibberish spouting fool, who did not have the slightest idea of what the fuck he was talking about. He asked me to comment, on the content of what the guy had to say.)

    Take a look at the date and time on this NewScience entry. This is an example of what we’re looking at, if the virus continues to circulate in its present configuration, and doesn’t undergo any significant mutational reconfiguration, during the second wave that’s just now beginning to express itself, in the Northern Hemisphere. I think that this is a large enough problem, just as it stands. We just do not need for things to get any worse, for us to be made to pay a fairly heavy price, here. Anyone who does not believe that this constitutes a problem is simply a total fucking idiot. The best case scenario, in all likelihood, is a bad fucking winter; a worst case scenario is a paralysis or collapse of most of our collective health care systems, in this country. Right now, a little more than 9% of the people in this country who have been hospitalized by this virus leave the hospital by way of the morgue. If this percentage holds (and there’s absolutely no reason that it shouldn’t…at the very least, that is), then, as the number of hospitalizations associated with this virus takes a dramatic upswing (that one is just about guaranteed, in the course of the next eight months), we’re going to see an increase in mortality. And the virus will not have to change one bit, to assure this outcome. All it has to do is be here. Now do you detect a genuine note of concern, here, on my part? And do you understand why I do not suffer fools gladly, as a result of this? This virus is extremely infectious; it does not have to be unusually virulent to kill a lot of people. If the virus exhibits a CFR between .064% (1.28 deaths per 2000 infections) and .128% (1.28 deaths per 1000 infections), and it manages to infect 1/3 of the US population this winter, then you could expect to see between 64,000 and 128,000 deaths from novel H1N1, this winter. Those figures are not exaggerations. This would probably translate into roughly 4,000,000 to 8,000,000 deaths globally; that would put this virus up there with the H2N2 virus that was responsible for the 1957 pandemic, when you factor in the change in population figures. That would be viewed as a “moderate” pandemic. Nearly everybody “out there” (with the exception of those who have already been exposed to this virus) has an immune system that is completely naive, with respect to this virus. That covers a huge amount of territory. Pandemic viruses arrive early (this one materialized in February or March, in Mexico), and they stay late (summer ends in the Northern Hemisphere on Sept. 21); we’re not quite into the normal seasonal influenza season, yet, and the first wave of novel H1N1 still lingers, while the second wave is just beginning to emerge. It’s been forty years since the last flu pandemic of the Twentieth Century; that was the mildest one of the three last century. This has resulted in some people drawing the conclusion (erroneously) that influenza pandemics are “necessarily” diminishing in virulence, and, consequently, in mortality. There’s zero evidence to support that conclusion. There have been, in fact, a number of relatively locally circumscribed (country or region) flu epidemics that have exceeded both the 1957 and the 1968 pandemics for general virulence levels. We’re going to see an increase in hospitalizations, and an attendant increase in mortality levels, until this second wave reaches its peak; I would expect that to be around mid or late winter (mid-February to late March; roughly 5.5 to 7 months out from where we are, right now. That’s just the way that it looks, from here.

    Click here: Don’t be fooled: swine flu still poses a deadly threat – health – 08 September 2009 – New Scientist

  2. #2 Christina
    September 9, 2009

    Revere: Thank you for such a thorough and easy-to-understand explanation of the research paper. Your analogy of the tokens was excellent. I so appreciate your willingness to patiently explain complex, important research findings, so that they are more accessible to laypersons like myself.

  3. #3 melbren
    September 9, 2009

    This is a link to the (2007) New York State “Allocation of Ventilators in an Influenza Pandemic Planning Document.” Although I have not read it recently, I remember being impressed at the time by its proactive, thorough, and transparent handling of an incredibly uncomfortable subject.

    http://www.health.state.ny.us/diseases/communicable/influenza/pandemic/ventilators/docs/ventilator_guidance.pdf

  4. #4 Catharine
    September 9, 2009

    My hospital has 9 ICU’s and often when we’re running at full capacity (which is most of the time), we have to dig out some of the old dinosaur ventilators (that have limited mode capacities). There is a task force for pandemic planning among the hospitals in our community (and I know things like linen shortages have been discussed), but we’re going to be facing some awfully tough ethical decisions when we run out of ventilators. What’s more, our hospital (like so many) is in the red and not only are we not stocking up, we’re cutting corners wherever possible (including no raises for any hospital employees – not executives, but the folks who actually work – for the next fiscal year). Now, having enough ventilators is one thing, but in my opinion (which, I know, means nothing), my major teaching/research hospital would do well to start being very, very nice to ICU nurses.

  5. #5 Jody Lanard
    September 9, 2009

    You cite New Zealand researchers’ data published in Eurosurveillance on July 2, which reported several ways of estimating the CFR of the emerging influenza pandemic.

    More recently, actual tentative New Zealand data was published in Eurosurveillance on August 27. It includes a very tentative New Zealand CFR estimate of 0.005% (with a clear explanation of how they arrived at that very tentative CFR).

    The authors also noted with interest that the 0.005% CFR estimate “is in the range found for seasonal influenza in the population under the age of 65 years (according to data from the United States [12] and various assumptions [11].”

    The U.S. CDC has never, to my knowledge, provided a tentative moving-target Case Fatality Rate. However, on several dates, they have provided rough estimates of total case numbers along with confirmed deaths.

    During this period, there have been hundreds of statements similar to this one in the PCAST report:

    “The case-fatality ratio (i.e., proportion of infected individuals who die as a result of the infection) appears to be similar to seasonal influenza”

    But it isn’t hard to to do rough calculations of the CFR in the U.S., using the CDC’s own confirmed deaths and estimates of case numbers on various dates. And such calculations do not produce a CFR “similar to seasonal influenza”, particularly if the New Zealand researchers’ citations about the average seasonal CFR in the under-65 age group is correct.

    Case estimate and confirmed deaths from CDC telebriefing May 22:

    “more than 100,000 people”, 9 deaths: CFR somewhere below 0.01%

    Case estimate and confirmed deaths from CDC telebriefing June 18:

    “hundreds of thousands of cases”, 44 deaths: CFR between 0.02% and 0.005%, using case range of 200,000 to 900,000

    Case estimate and confirmed deaths from CDC telebriefing June 26:

    “for sure there’s been more than a million of these new infections… The million is estimating the symptomatic”, 127 fatalities: CFR less than 0.013%

    Case estimate and confirmed deaths from Wall Street Journal (medical writer Betsy McKay), August 18:

    “More than two million people are believed to have contracted the new flu in the U.S… and 477 had died as of Aug. 13, according to the Centers for Disease Control and Prevention.” CFR less than 0.02%

    The CDC continues to talk about a very narrow range of scenarios vis a vis the pandemic. CDC officials do not contradict all the statements about “what is” by reporting an apparent current overall tentative CFR lower than the seasonal flu, but perhaps higher than the seasonal flu in the age group most affected.

    CDC and HHS officials also do not vividly and dramatically talk about “what may be” if the virus becomes more virulent. They initially downplayed even a mild pandemic scenario with an upper limit of 90,000 deaths (the PCAST scenario that made uninformed people go “Oh my God!”) – which is only about 20,000 more deaths than in a bad non-pandemic flu season:

    “When you look at individual seasons, the death totals from influenza can vary a lot, and they can range from really very few measurable deaths to, in bad years, up to 50,000 to 70,000 deaths… The 36,000 is the average number but the range can go up as high as 50,000 to 70,000 deaths in bad years.” — Keiji Fukuda, then CDC flu expert, 2003

    The math of swine flu “what may be” is indeed depressing. If it gets worse, there may come a point (and probably not an endpoint – that would be too coincidental) when it is “similar to the (average) seasonal flu” in deadliness. At that temporary point, the CFR will be about five times as high as it seems to be now. How will officials explain it, when they have been saying all along (or letting others say, without challenge) that “The case-fatality ratio … appears to be similar to seasonal influenza”?

  6. #6 revere
    September 9, 2009

    Jody: All good points to which I have no answers. I hope CDC does.

  7. #7 melbren
    September 9, 2009

    Have you hugged an ICU nurse today? Good. We don’t want them to get the flu right now. (As Catherine notes–let’s pay them well and treat them well, instead!)

    The link below is for a fascinating article that appeared in the Atlanta Journal Constitution on July 9, 2009, describing the severity of illness in Georgia’s first swine flu patient. (She was from Kentucky, however, and is officially counted in Kentucky’s statistics.) This patient survived only because she was transferred from a smaller regional hospital to Emory University Hospital in Atlanta–which is literally next door to the CDC.

    Clearly, this patient received extensive and extraordinary care– including several weeks of mechanical ventilation. Surprising even her doctor, she survived the ordeal. But if a similar scenario were to play out among a lot of patients at one time, it is very easy to understand how our supply of ventilators–and the wonderful ICU nurses who are trained to operate them–would be depleted very early on.

    Keep in mind, the swine flu patients who are seeming to require mechanical ventilation are apparently requiring it for extended periods of time. The mathematics of the situation are indeed bleak. Three or four critically ill patients a week requiring three or four weeks of mechanical ventilation, is not a scenario that bodes well for any severely ill patient–swine flu or other–who shows up at that hospital in week four.

    http://www.ajc.com/ajccars/content/metro/stories/2009/07/09/local_swine_flu_patient.html

  8. #8 antipodean
    September 9, 2009

    Thanks Revere. That was a mighty fine example of scienceblogging.

    Would you, as an editor, accept a paper that had data analysis undertaken inside excel? It does some very kooky things from time to time.

  9. #9 revere
    September 9, 2009

    antipodean: Using Crystal Ball with Excel is standard for Monte Carlo Analysis. Most statistical work is just multiplying, adding and dividing, with some exponentiation thrown in for good measure. Excel is perfectly fine for that. It also does standard statistical tests. Having said that, I use R for my work.

  10. #10 BostonERDoc
    September 9, 2009

    So the next thing to talk about is triage into ICUs. Who gets in and who doesnt. A number of grading systems have been developed and proposed. The Institute of Medicine will likely address this in their upcoming degradation of care session. Here is an intereesting read or as Capt. Kurk used to say: “Required reading at the Academy”
    http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2206465

  11. #11 antipodean
    September 9, 2009

    Thanks Revere

    I’ve seen it screw up adding, multiplying etc. I had heard years ago that it was not appropriate to analyse scientific data in Excel for this reason. Data entry, fine, but nothing more.

    I suppose they may have fixed the bugs since. I just wondered whether this was in your editorial experience.

  12. #12 o.jeff
    September 10, 2009

    They should have halted seasonal flu vaccine production as soon as the pandemic strain was isolated and used all production resources for the novel H1N1 vaccine. And then done everything possible to speed the vaccine safely to market.

    There are millions of lives on the line, but precious weeks and perhaps as much as two months appear to have been wasted for no good reason. We could have tens of millions vaccinated by this point in time.

    Have we applied every possible resource this country has toward speeding this vaccine safely to the people? Has every minute been utilized? Have air force jets flown samples from laboratory to laboratory instead of wasting 24 hours on Fedex? Have workers worked 24×7?

    Where is the vaccine right now? Why isn’t it being distributed as some batches complete? How many days are going to be lost because of inefficient distribution?

  13. #13 revere
    September 10, 2009

    o.Jeff: As always, it is not so simple. First, we started immediately on the effort to make the vaccine (see our post here on why it takes so long. Halting seasonal fu vaccine would have made no difference. No time was wasted. Second, it was not clear then (nor is it certain even now) that there won’t be co-circulating seasonal flu. The heaviest toll from seasonal flu is in the over 65 age group, who probably will benefit the least from the swine flu vaccine. If there is any significant amount of seasonal flu around it will hit this group the hardest. Third, we make little vaccine in this country. Pretty much we are buying it from other countries. Talk to Big Pharma about that. We should have a national vaccine institute that makes public vaccines, not a privatized market. We used to do this with DPT vaccine. Fourth, as we have noted often, our public health infrastructure is in dire straits because people wanted a couple of extra bucks in their pockets from cutting taxes rather than investing in the system that will be needed to administer and distribute the vaccine. So all of you who wanted lower taxes, try taking the few hundred dollars you saved and use it to buy some public health protection for yourself. It’s your money, so you must know how best to spend it. Go ahead. Buy yourself some police, fire and public health.

  14. #14 Philip D. Brown
    September 10, 2009

    While there is a limited threat from H1N1, the real threat remains H5N1, which is so extreme that no epidemic in human history comes close to its projected lethality. So right now, some of the measures for H1N1 are being used as a dress rehearsal of the reorganized health infrastructure made to confront H5N1.

    That being said, much of the mortality associated with H5N1, and to a far lesser extent with H1N1, is due to what should be considered a companion syndrome, ARD. It is important that the two be distinguished, because each requires their own course of treatment, to a great extent independent of the other. It will be insufficient to try and prevent ARDS solely by attacking the virus.

    For this reason, there is an effort to create a formula of hopefully OTC drugs that can inhibit enough of the 150 or so cytokines and inflammatory mediators to prevent the development of ARDS in the first place. Since ARDS normally exhibits on about the fifth day of symptoms, ideally this formula should commence as soon as they manifest, and continue until the virus has run its course.

    The initial proposed group of four medicines to “fend off” ARDS include Histamine-1 and -2 blockers, an ACE inhibitor, and ibuprofen as a prostaglandin inhibitor. Since ACE inhibitors are Rx, Vitamin D3 has been suggested as a replacement. It also has several other beneficial effects, including antiviral properties.

    Importantly, please note that this is a theory, that as of yet there is no established prophylaxis to ARDS. But because of the potential critical shortage of mechanical ventilators, it is vital to develop some means of preventing its onset.

  15. #15 revere
    September 10, 2009

    Philip D. Brown: Yes, we’ve been covering this for almost 5 years. The question of dealing with the immune dysregulation (inaptly named cytokine storm) is quite complicated. Dave Fedson has been promoting statins and more recently rozglitazone. Neither are OTC but the statins are cheap and plentiful. But at the moment we don’t understand the pathogenesis. If you click here you will see many of the posts we have done on the biology of H5N1 that bear on your point.

  16. #16 Barnaby Dawson
    September 11, 2009

    The Eurosurveilance paper assumes for three of its CFR estimates that every death is reported! But in the US a more typical reporting figure for seasonal flu would be 5%. And its not at all obvious that that many more deaths would be reported for swine flu than for seasonal flu. I would argue that some factors make reporting a given death more likely for swine flu but other factors make it less likely. In particular the requirements for reporting swine flu deaths are pretty strict. Much more so that for seasonal flu.

    On balance I would guess that reporting is higher than 5% in the western world. But the eurosurveilance article makes one hell of an assumption here by assuming a 100% reporting rate!

    The fourth CFR estimate from the eurosurveilance paper essentially assumes that the death by age profile is the same for seasonal flu and for swine flu. This is also a dubious assumption.

  17. #17 Medclinician
    September 12, 2009

    This is a good article Revere. As a nurse I can tell the entire ventilator thing is grossly askew in terms of effectiveness during our Second Wave of the Pandemic. Besides having or not having enough vents- we don’t have the places to put them really, and you will note we were ambu bagging patients, not venting them when there was no power.

    You need someone – often one on one to run a vent on a patient sick enough to have one. If you have worked in RT- the consistent build up of mucous- which essentially killed Reeves (superman) is why you cannot just blissfully flick the switch and run down to ER. Vent patients need airway TLC and blood gas monitoring and a lot of medijargon for high acuity- (nursing care by 1 assigned nurse at times ) like an HIV patient- to keep them alive.

    In triage, in a Pandemic, most, and we were discussing the humaneness of this statement they would go in the ‘deads’ area. Those who consume too many resources. On media, and I was told this by an insider during a press conference at a large hospital where the fussed around with one girl while ignoring about a dozen ill patients, to demonstrate the the TLC (tender loving care) flu vicitims would get.

    Rethink. They will get TLC – not. They will be told to go home and SIP. We don’t have the resources to take care of masses of flubies. Cold.

    Yea, kinda. Military slant here. Well those in ‘Nam understand, especially doctors. You put your real possible fighter back up on the line and use your drugs and sutures on them as opposed to a Catch 22 guy with a lifted up blanket and viscera exposed bleeding a lot. That is last rights time. If you have a chaplain.

    Vents and even the concern with them during a Pandemic are a walking in the .0x% Disney world which is unlikely.

    Wouldn’t it be nice- as sang by the Beachboys- but sorry no cigar. You are going to be for the most part- on your own.

    Medclinician

  18. #18 Dr Attila Danko
    September 13, 2009

    What about intravenous antivirals? There have been about 3 recent case reports on the use of intravenous zanamivir which have seemed to be very effective in very sick ventilated patients, the best documented one was recently in the Lancet. (full view requires subscription but this news article is good)

    http://www.rtmagazine.com/reuters_article.asp?id=20090904clin003.html

    IV peramivir is likely to be just as effective.

    We use IV antibiotics all the time, why has it taken us so long to look at intravenous neuraminidase inhibitors?

    How about administering IV antivirals to hospitalised patients with influenza as part of an urgent trial? Should be easy to set up. It’s not some wierd new thing and we have good Phase 1 data at least. There is a very good chance that high levels of NI in the bloodstream will get people better quicker and reduce ICU admissions, it’s at least worth a trial before the Northern Hemisphere influenza season gets under way with a vengeance.

  19. #19 revere
    September 13, 2009

    Dr. Danko: There is definitely a place for IV antivirals for treating seriously ill patients. The problem is that (aside from the fact of the regulatory issues as none are approved yet) we don’t know how well they work. Nothing I know of is “very effective.” Antivirals don’t attack the virus in the same way antibiotics attack bacteria because viruses aren’t alive and don’t “grow” on their own. And anyone that seriously ill and in a hospital is also likely to be a candidate for a vent. So it is an adjunct, not likely a replacement for vents. And no clinical trial is easy to set up. They are all difficult and if not done with care you wind up not getting the information you want and need. There is also an ethical issue. Are you going to substitute them for vents?

  20. #20 Dr Attila Danko
    September 13, 2009

    Revere: Thanks for your response. In the case reported in the Lancet, the ventilated patient recovered 48 hours after initiation of IV zanamivir and methylprednisolone; this was 16 days after trying everything else, including nasogastric oseltamivir and nebulised zanamivir, and little improvement in the patients condition. Improvement after 48 hours seems “very effective” to me. Depends on your definition of very effective I suppose. I apologise for having a front line clinician’s view on this.

    Read the original paper if you can.
    http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)61528-2/fulltext

    The Dr’s reasoned that poor absorption from the stomach and atelectatic lungs meant that IV antivirals were the only way to produce high levels of drug in lung tissue. Since cortisone was already tried without success on day 3-6 it is unlikely to have been the steroids alone which helped.

    Of course antivirals do not work exactly like antibiotics but clinical improvement can be just as rapid, depending on the circumstances. I myself contracted H1N1 and made a rapid improvement (within a day) on commencing antivirals hours after getting sick. My patients with herpes infections often get better very quickly if treatment is initiated promptly.

    The trial need not have any ethical issues such as you mention. Randomise hospitalised patients with proven influenza to either oral oseltamivir or IV zanamivir (can be double blinded with placebo IV solution and placebo tablets) and measure how many eventually need to be ventilated. Or else if already ventilated, measure time to extubation, and overall mortality. Seems straightforward to me, and the stakes are high; but then again, I accept I am just a clinician and do not understand the difficulties of setting up a definitive trial. I can’t get away from the nagging thought that this might not have just been co-incidence, of course a trial is necessary to answer that question for certain.

    If your hypothesis is that antivirals are of low effectiveness, and the patients recovery was co-incidence or steroids, it would still be a good thing to do such a trial. We would want to stop clinicians wasting resources on untested and potentially useless IV zanamivir or peramivir on the basis of a few case reports. I bet I’m not the only one reading this and getting excited and possibly falsely hopeful.

  21. #21 Dr Attila Danko
    September 13, 2009

    Even if you simply reduce time required on ventilation you increase your effective number of vents.

  22. #22 M. Randolph Kruger
    September 13, 2009

    Without comment as to why, Methodist LeBonheur here in Mempho has set up triage tents on the grounds of the hospital. I blew in there delivering a helluva lot of ventilation gear. It was some new ventilation gizmo that can do four or five people at once in a circular ward arrangement. Its BIG with central powerbox, heart monitors, a multibank of oxygen bottles. Several Craftsman rollaways with enough drugs in them to place it on a druggies target list.

    There was also one crapload of general oxygen masks/vent tubes in boxes. It was just going up last week and it made the papers of course… But is it being used? Somewhat from what I gather.

    The ILI graphics sent to me by DemfromCT indicated that we were on a meteoric rise (thx Dem), way past background, way past what the doctors office can handle and a bit of a line starting to show up at the ER’s.. Nothing yet to indicate we are over capacity or over the peak of the cases either. I dont know but the idea is to keep the bug outside on the lawn if they can and the hospital clean obviously.

    My problem?

    They hadnt restricted access to the hospital at all. Triage and treat on the concrete and not close the front door? Wonder what they will do if it gets ugly, hold swine flu infection parties with the kids in the tents and Bozo the Clown as a guarantee of a show up of parents?

  23. #23 wb
    October 2, 2009

    to all those on the left spectrum of politics, quit trying to scare the american people about a flu that to date has nowhere near the virulence of a common strain of flu. get this, i have been unable to locate a single hospital that has been swamped by this flu. out of the 284 hospitals we have contacted only 5, had admitted more than a dozen cases, only 5. where are you people getting this info? given the limited amount of bed space this time of year 200,000 people admitted, as this article suggests, would have health officials screaming their heads off. please, quit the scare mongering people, especially those in the media who are outright lying about this so called epidemic. the truth is there are likely to be far more deaths and complications from taking this vaccine than if you get sick and let the disease take its course. will some die, yes. that is unavoidable with any type of influenza. what most fail to realize is that the government is pushing a vaccine that has not been adequately tested. the military has been ordered to take this shot. let’s at least see how it affects them. the risk here of contracting a serious side effect here is just too great. even the leadership at the cdc, when pressed, would not say they were confident enough in this vaccine to take it. to date, more than 40 per cent of all doctors and nurses now say they will refuse the shot. maybe they know something the talking heads of the media do not? the feds tried this same thing back in 1976 and alot of people wound up having severe complications before that swine flu vaccine was pulled. if this flu is so virulent, especially since it has to date been so benign, is there something our government knows it is not telling us? like it or not people, biowar labs do exist and influenza can be used as a weapon. if this were the case do you really think your government would come clean and admit to a screwup? really? with an election hanging in the balance do you really think a policitian would voluntarily come forward and admit to such? if you do then i think you are the individual living in fantasy land. something to think about.

  24. #24 revere
    October 3, 2009

    wb: Actually this is a moderately virulent virus, using seasonal viruses as a standard. That’s hardly the point. I would suggest that you are the scaremonger with your point that the vaccine hasn’t been sufficiently tested. All of the US licensed vaccines are just a strain change, no different than any other year. I don’t know what you mean by “sufficiently tested” but I doubt you do either. We’ve posted here often about the infeasibility of testing any pharmaceutical for rare events ahead of time, but what such events there might be with this vaccine there is no reason to think that they are different than any other seasonal vaccine. What makes this strain different is its epidemiology, not its virulence. So by your own argument, this is just the usual flu vaccine with a virus you think isn’t even very bad.

    Doctors and nurses are just like everyone else when it comes to vaccines. Some of us know more because we’ve made it a point to find out, but for most all they know is what they hear, and if they were going to listen to the vaccine scaremongering crap you are peddling they’d be dangerously misinformed.

    No one is going to get admitted to a critical care bed if they don’t need to be in it because a doctor has been “scaremongered”. But a lot of people may not get admitted to one because there isn’t one.

  25. #25 hana
    October 6, 2009

    According to a recent blog post in Flyp magazine…

    Right now, in New York at least, a doctor is prohibited from removing a patient from life support unless they or their family have decided to do so through a living will or advance medical directives. As ProPublica reports, “New York officials are studying possible legal grounds under which the governor could suspend a law that bars doctors from removing patients from life support without the express consent of the patient or his or her authorized health agent.