Swine flu: the overreaction overreaction

I hope that this turns out to be a dress rehearsal of sorts and that we take advantage of the front row seats, to build some algorithms that we can use with some confidence for the next wave or next event, to eliminate some of the energy sapping speculation and hand wringing, that we've had to (and still) endure this time around.
We will have good hard data to draw on and we need to leverage it to the max.
Just like in the markets,"charters" aren't always right, but at least managers have more sound and accepted defenses for failed or inefficient trading strategies,as would clumsy world and local public health agencies.

The "overreaction" I've seen has been primarily televised. On blogs, Twitter and other networked media, the coverage been mostly informative and responsible, with commenters displaying a philosophical, even humorous attitude toward what is a fact of biology.

Actually, even the news segments on TV have been OK. It's the talking heads with airtime to fill and the promo guys with ratings to garner who have created the "frenzy" with things like "is swine flu the new black death?" "Could millions die?"

Perhaps the populace that elected Obama is a little smarter than the panicked mob portrayed in media. I'm betting readers of this blog are. So spread the meme: When public health works, nothing happens.

is it true?
this thing can die out and its not really very potent?

time will tell the story but this looks, not so bad eh?

QUOTE : http://www.newscientist.com/article/dn17072-first-genetic-analysis-of-s…

A mathematical model permits the calculation of an important variable called R0 â the number of additional people infected, on average, by each case. If R0 is less than one, an infection dies out.

Grassly also cautions that the estimate is very preliminary. But with the data available now, he gets an R0 of 1.16 â enough for the virus to keep going, but only just.

This could be good news. In epidemiological theory, at least, the lower the R0, the easier it may be to snuff the virus out by further hindering its spread.

this maybe why we're seeing fewer deaths and cases in Mexico, because they took the threat seriously and did what they could to cut off paths of infection.

QUOTE : http://in.reuters.com/article/health/idINTRE5410TS20090502

New laboratory data showed fewer people have died in Mexico than first thought from a deadly new influenza strain, a glint of good news for a world rattled by the threat of a flu pandemic.

Mexico cut its suspected death toll from the H1N1 flu to up to 101 from as many as 176, as dozens of test samples came back negative. Fewer patients with severe flu symptoms were also checking into hospitals, suggesting the infection rate of a flu that has spread to Europe and Asia was declining.

I just hope we dont have to do exactly the same thing here in the US to get the same results. (:

I collected a few of my favorite over-reactions and played them on my radio show last Thurs evening. Including.

1. Goddidit
2. Illegal Aliens diddit
3. Terrorists diddit
4. Terrorists used Illegal Aliens to do it
5. The US gov't diddit

Enjoy:
Birdmonkey Mad Swine Freakshow: Level FiveAlert

I'm a Mammal and so are You - artist unknown
Cooking MonkeyBird Swine Flu with God and Jebidiah Scooter
Piggies: music by the Beatles
Blackbird: music by the Beatles
Alex the Jones: makes things up for radio
Audio from 12 Monkeys
Monty Python expecting the Spanish Inquisition
The usual bed wetting audio fear from the ever-trembling Michael the Weiner
Sucker Feat: music by Peeping Tom
I was a Communist for the FBI- vintage radio with Dana Andrews
Little Box of Magic: music by Githead
Soundbed throughout was Valvogoth by Just-John
music director this week-John K Fitzpatrick

Innerside Radio Program produced in Houston for KPFT Pacifica Radio. download from http://acksisofevil.org/innerside.html

xarkGirl: I think you haven't been on the Internet sites where the average Joe hangs out. For example, read the comments to this newspaper articles: http://breakingnewsblog.dallasnews.com/archives/2009/04/dallas-elementa…

and

http://breakingnewsblog.dallasnews.com/archives/2009/04/in-schools-too-…

Cautious skepticism mixed with common sense is my suggestion. Swinging wildly between terror and complacent relief doesn't help anything. It fails to take into consideration the uniqueness of this particular virus, or the tendency of viruses to drift and even shift, while at the same time stirs up a lot of baseless panic and scapegoating. WHO is taking the right road. The media, however, is just looking for a circus to flog, as usual.

Very glad that revere reported this, and please continue to report it in all posts.

"...excess mortality caused by influenza yearly in the US is around 35,000 to 40,000."

Some of the over-reaction is because the MSM has not told people this fact. If the information is incomplete, the understanding is incomplete.

Very good points. Essentially those in charge of public health are in a no-win situation (except by doing their jobs well we all win in the end by fewer getting ill.)

I work in the IT industry and what worries me is if a pandemic happens, particularly one with a high excess mortality, and public health officials do not do what needs to be done the results will be devastating to an already severely weakened world economy. Most people do not really grasp how critical skilled IT staff are to running the modern world. Our whole communications, transportation, energy, economic infrastructure depends on IT and particularly on people who understand,and build, complex networks, and those that know how to manage the telecommunications gear (routers, switches etc) and SCADA network gear that make those networks possible. This is a tremendous vulnerability in our modern world.

Good post.

24hr cable news will no doubt be a contributing factor in the destruction of civilization. Speculation is only played out there. In the real world, seems like everyone is doing their job. I'm impressed with our gov'ts and international organizations level headedness.

There was an interesting anecdotal post on Dkos about emergency rooms in a Pa community being overwhelmed with local immigrants who were afraid they may have the flu, but lacked primary care physicians to go to. It's something to think about should this flu fully blossom. (Not for the immigrant response, but for all of us.)

I have to admit, I haven't thought much about the cost of Mexico's response. I thought that's what responsible gov'ts do for the sake of their own citizenry. We'll see what happens here as things progress. I may be more appreciative of the Mexican gov'ts efforts.

Thanks.

engstud: What is true is this: this virus can do anything. That's the nature of influenza viruses. So what is it likely to do? The range of likely scenarios is narrower than "anything" but still pretty wide. At a minimum I would say the most prudent thing to do is prepare for what might be an extremely bad flu season next year. An extremely bad flu season would be a very bad thing, although neither unprecedented nor a catastrophe. It would be a very rough ride in current circumstances. We can get ready for a better ride if we start immediately to prepare for it. Meanwhile we have to keep an eye out for what this one is going to do. Right now it still seems to be gathering a head of steam. We should have a fix on R0 relatively soon. The 1918 flu and an R0 or 1.7 to 3. Measles has an R0 of about 11, for comparison. So R0 doesn't have to be very high to have a problem. Too early to speculate on this.

As a non native english speaker and overviewing emerging diseases and pandemic preparedness development for six years I observe good and quite sad things at the same time.

Mexico behave as a responsable Nation in being swift and bold even in these "case sensitive" issue as SIP (Sit in Place), School closures, shutting down non essential activities in Mexico city, it has been a courageous move indeed and an economically costly one.

When I look via the Spanish Languages, they are more fearfull and less aware of the International Level of Public Health Solidarity of Mexico. Sadly by the of the day, about a million of Mexico City Residents will have gone out to regions for diverse reasons contrary to the advice of their President.

In Europe trough French, Italian and German on-line news, we are witnessing finnally the end of public xenophobia comments against Mexico and Mexicans.

Despite all this there is an emergence that there is only one human specie, it lift up the Hopes in Humanity and Humanitarian Governance.

Snowy

I agree on the possibility of backlash. If measures succeed it won't seem like the threat was real. That's the same issue we are seeing with the anti-vaxxers. They think infectious diseases aren't really so bad....

I've been wondering if their heads were spinning about the possibility of having to choose between H1N1 vax for their kids or the unknowns of this flu (or subsequent versions). But we don't hang out in the same places so I'm not following any of that discussion.

Funny to watch WHO chastize people for going to ER rooms after going from 3/6 to 5/6 on their pandemic Phase threat level. It is like lowering interest rates prematurely. WHO is saying panic, but don't stress medical resources. lol.

here are some immediate complaints of overreaction by hotel guests in Hong Kong quarantined -

http://www.monstersandcritics.com/news/health/news/article_1474559.php/…

this would make a good post of its own...what disturbs me most is that the guests heard from news reports that they would be quarantined for a week instead of the 24 hours that they were first told be the authorities...

Joe

Revere you me and everyone have been broadcasting R0 predictions for a week. I probably had it too low and you and everyone else in the blogosphere too high. I was thinking 1.3 initially (around Sunday I figured it should be spreading faster than the blogosphere's panicked assessment), and maybe 1.5 now (reread last Saturday's pub-med mailing list report on Monday and realized Mexico was only reporing pneumonia patient admissions). Your earlier insistance of widlfire spread suggest at least around a 1.8-1.9 prediction. I don't see harm as long as one doesn't suggest their R0 guess is based on hitherto unknown results or analysis out of Winnipeg or Atlanta or ground crews in Mexico.

Revere I think this post should be relevant to the current situation.

Epidemiological evidence of an early wave of the 1918 influenza pandemic in New York.

I post that in 2006 at
http://www.flutrackers.com/forum/showthread.php?t=12932

Lots of datas but hard work done by them in those days.

Thanks for everything

Snowy

very good points. Essentially those in charge of public health are in a no-win situation (except by doing their jobs well we all win in the end by fewer getting ill.)

i am working as teacher. i got good information from ur site.
thank you

It's the Y2K syndrome: everyone makes jokes about all the anxiety leading up to the calendar rollover. What they ignore is the hundreds of millions of hours spent to head off those computer failures.

Same here: if it fizzles, public health gets a black eye for needless precautions. If it blows up, public health gets a black eye for not doing enough. Worst case scenario: it fizzles, then come autumn people ignore warnings when it really matters.

Hi Revere you can compare the previous message with this

From Copenhagen at

Roskilde University, Denmark

Historical records suggest that an early pandemic wave struck Europe during the summer of 1918

cf: http://www.flutrackers.com/forum/showthread.php?t=89666

Snowy

Philip; I don't remember making any R0 predictions (at my age, though, memory is weak reed to lean on). My points about the potential for number affected and speed, however, weren't related to R0 but to the number of susceptibles and the generation time. I think we should get a handle on R0 soon, as its definition is avg. number in an entirely susceptible population, which is what we are observing. For the usual seasonal virus, R0 is underestimated because of herd immunity and you have to do special studies to estimate it. What I am hearing now is that this virus has about the same transmissibility as seasonal flu.

You can't even begin to reliably assess RO (or much of anything else, for that matter), when it is clear that the testing system, which is a natural bottleneck, at this point (probably everywhere) has fallen behind, and may continue to fall further behind, if this thing surges at all. If this had been even a "moderately" virulent pathogen (an order of magnitude beyond seasonal flu, for example), what we would be looking at, at this point, would be utter chaos. We seem to be in a fairly "good" space, for the time being; but as Revere persistently articulates matters, here, we have no idea at all, with regard to where this thing "could" go.

How long does the test for H1N1 take to run? How many samples can be running at once at the CDC lab? With the pipeline full and new sample intake at maximum, how many results can they publish per day?

As a layman, I would have expected 10,000+ samples per day intake capacity.

Soor Revere. I assumed your initial calls for immediate WHO Phase upgrade was based on an assumed implicit R) guess. I still think this is true for most initial predictions. People haven't used the R0 term because leaders and media didn't know what R0 was but it is clear to me the hyped upgrade to Phase 10000 calls last week were based on R) predictions even if couched in informal words.

As an aside, I'm surprised WHO redifined their Phases (I liked old ones; IV is sustained P-to-P spread, not just from Mexican travellers coming home, in two regions and V is three or more regions) without making some consideration for mortality rate. When people see Phase numbers rise, I assume they think their odds of death have increased.

Excellent post.

The media still abrogated their responsibility to provide some context. i.e. an explanation of transmissibility vs. virulence. That would have mitigated some of the panic and allowed for a calmer discussion.

Thanks for supplying some of that context above.

Jay Gordon

you know I was just wondering about transmissibility vs virulence and found a previous post on this blog on r0 during the h5n1 events informative.

Its amazing how much information is on this blog and in a fairly easy to understand form. Its a beautiful thing.

I'm what many here would call a "right wing xenophobe" yet I was the only one calling for measures that would have provided an early, inexpensive and accurate measurement of the CFR (no -- no the council on foreign relations).

The cost of uncertainty in the CFR is enormous so it is profitable to make enormous investments in reducing it, yet the cost of what I was proposing (swabbing Mexico City hospital staff) would have been perhaps $100k.

It didn't get done -- probably because folks in the CFR and their toadies were too worried about "right wing xenophobes" to actually work on the key pertaining to foreign relations and public health.

"and while we have no hard figures, good estimates of the excess mortality caused by influenza yearly in the US is around 35,000 to 40,000."

Revere

This number seemed to appear 'out of thin air' a couple of years ago...Do you know whom in the United States is responsible for this number and by what mechanism they came up with it?

Thanks

Tom, it's from CDC and Lone Simonsen.

http://www.bmj.com/cgi/content/extract/332/7534/177-a

Tom: Yes, this is a CDC estimate based on modeling a time series of pneumonia and influenza (P&I) deaths using Serfling's Method. There is no way to directly count influenza only deaths because death certificates only record a small proportion o f them, for a variety of reasons.

Here is a rough personnal translation from France Romandie News.

(©AFP / 02 mai 2009 19h19)

http://www.romandie.com/ats/news/090...7.yhw93yrx.asp

H1N1: WHO do not know the gravity of the pandemic.

GENEVA - WHO "do not know to wich level the H1N1 virus can be grave or mild", said a responsable of the organisation who has estimate that the evolution of the situation in the next few days in Europe will be determinative.

"The degree of gravity is not fully establish", declared Dr Michael Ryan, director at the WHO World Wide Network Alert and responses in a pandemic(GOARN).

World Health Organisation (WHO) declared last wednesday alert Phase 5 to emphasize that a pandemic is imminent. The maximum Level 6, that has not yet been declared describe State of Pandemic but not its gravity degree underline Dr Ryan.

The Mexican Government estimate on Friday that the virus was not as aggressive than feared and that the epidemic is in a stabilisation phase with cases count unchanged at 16 deaths in the country.

From the HQ of WHO in Geneva, Dr. Ryan has called to be prudent in the evaluation of the situation.

"When remembering the case of SARS or other epidemics, you can realise how difficult it is to, at this stage of the epidemic to make an precise estimation of the gravity of the disease provoqued by A (H1N1) he emphasized.

"I do not criticise the government of Mexico who has to face a complex situation and who was exceptionnally cooperative when we asked informations, said Dr. Ryan.

The evolution of the situation in Europe in the next few days will allow to determine the extent to wich the mutated virus has propagated in a new continent, sine qua non condition to raise the WHO pandemic alert level at the maximum 6, estimate Dr. Ryan in the press conference.
"Actually, I will reiterate that a pandemic is imminent because we see the disease spreading.

But we have not yet establish a sustain transmission (outside North America). At this stage, we should expect that level 6 be reach but we Hope it will not be he added.

Une transmission "soutenue" signifie que "la maladie se répand profondément dans une population, et pas seulement au sein d'un cercle familial", a expliqué le Dr Ryan.

Measures taken to treat H1N1 cases among travellers getting in Europe from Mexico or the U.S. seems to have been efficient stated the Director of GOARN.

"At this moment, it would not be recommended in any ways to suggest that these events are not under our control", he said. "I think that within the next few days will tell us" where the situation will be said Dr Ryan.
"We have no proof of a propagation in a population outside North America" he said.

(©AFP / 02 mai 2009 19h19)

http://www.romandie.com/ats/news/090...7.yhw93yrx.asp

People talk about R0 as though it was a property of the pathogen (in this case, the specific strain of H1N1 influenza A). It isn't.

R0 depends on the pathogen but also on the characteristics/behaviour of population within which it may be spreading. As such, it can be reduced through prevention measures - which could mean anything from basic use of tissues + handwashing to drastic "social distancing" plus quarantining of anyone with symptoms.

We need to be out there promoting basic measures which don't really harm the economy, to avoid reaching a stage where we might need more drastic approaches.

Hilary: You are completely correct. I think when some of us talk about "the" R0 of the virus we are speaking of the outbreak now as it is unfolding. In a sense it is easier to estimate in this setting because the population are all susceptible. But you are correct: R0 is a product of host, pathogen and environment (in this case, including measures to reduce transmission).

Thanks Revere.

Has Serfling's modeling method every been questioned or checked as to its modelling accuracy?

While we have discussed CFR, I don't remember any discussion of hospitalization rate. My local NBC put an article on their web site stating that 13 people have been hospitalized in the US and that there are 160-170 confirmed cases.

This would lead to a hospitalization rate of 7.6% (assuming the 170 number). Even if you lump in the suspected cases, the number goes up to 721 (numbers off of wikipedia - not the best source but I don't know where else to get them). Then the hospitalization rate is 1.8%.

I haven't been able to find adult hospitalization rates but I found children numbers for past years on CDC's web site. Infants/Toddlers have a rate of .03%, but older children are only .01% University of Utah put out some numbers for infants only and the range was .5% to 1%. They also stated that rate is higher than the senior citizen rate. From my reading of the CDC web site, I don't see that they gather hospital statistics for adults and the flu.

This seems to contradict the "mild flu" it is being called everywhere. However, I see several possibilities:

1. That 13 number is wrong - it was the first time I've seen a number given by anyone.
2. I made a math mistake.
3. There is a bias right now in people being admitted in borderline cases instead of being sent home.
4. It is a more severe flu than it is being given credit for.
5. Some combination of the above.

Thanks DemfromCT

/:0)

Tom: No, there is no way to validate it with current data, which is why it is used. Crudely it takes flu season P&I mortality and subtracts off background (non flu season) mortality to see the excess. It does this over many seasons. It is an entirely reasonable way to get excess mortality from flu but not perfect. So it is the best estimate, not a census. The alternative would be to use data you know are a gross underestimate or try to do better using ancillary data that is reliable.

"Crudely it takes flu season P&I mortality and subtracts off background (non flu season) mortality to see the excess."

The problem with this type of epidemiology is that other pathogens also mimic influenza in the sense that the mortality from them also goes up in 'flu season'.

"The alternative would be to use data you know are a gross underestimate or try to do better using ancillary data that is reliable."

Which is better...a gross over-estimate from Serfling's model...or a gross under-estimate?

Maybe a more accurate model would be to average the gross under-estimate and Serfling's model gross over-estimate.

Unfortunately, this estimate has been taken as truth (not an estimate)around the world and used by a number of regulators and Governments including my own in Canada as an excuse to do nothing...

the most expedient way to downplay the risk of a pandemic...and not only a pandemic, I have seen it used to downplay food poisoning and the lack of regulation here as well.

In fact, that is 'tool' what it is being used for right now by the CDC and the Health Agency of Canada and by the World Health Organization to downplay both the risks of H5N1 and Swine Influenza...

...kind of as that epidemiological Alcohol consumption model, produced by epidemiologists for the Alcohol industry that surprise, surprise has increased consumption (and profitability) many many times since it was also widely reported and used to great advantage.

When it comes to influenza, the fact of the matter is that nature doesn't give a ****...

...or in other words...

Epidemiologists say: "Thin out sick chickens"

Virus says: "Thin out stupid people"

(Racter 2006)

Since people are so enamoured of R0, and the consequences of it. It is entirely possible (and indeed almost certain), that different pockets of the population will have different values. This is a consequence of the fact that the factors that influence R0 are not constant over the whole population (or with time). It only takes a few small semi-isolated pockets with local R0>1 to sustain a reservoir of virus. Thus even if we get some globally measured value of R0<1, i.e. we see a decreasing global caseload, these reservoirs have the potential to re-ignite the epidemic once R0 is allowed to increase. This could happen either/or because of a change of season, or because of complacency. The only strategy that I would recommend at this time is to remain vigilent until a vaccine is available and a significant fraction of the population has recieved it. With any luck we can hold the infection rate down until that time.

In 2006 you wrote about the Rumsfeld/Tamiflu connection. I see the meme being brought up again today.

Thoughts?

The irony is that the overreaction backlash will be more severe the more successful the public health measures are

This sounds like the same argument that Bush used in defense of his draconian "anti-terror" policies. We 'haven't had a terrorist attack because the policies were so necessary'

Though I am in the computer field, I do not accept the excuse that the reason that the Y2K problem was a bust was that it was so effectively treated. It was NOT effectively treated, it was a pork-filled panic driven employment opportunity for half assed programmers. The bottom line is, though there were some critical systems that had to be prepared, these were already under the radar. The extensive reviews were largely and expensive waste of time. There were still some systems that had problems and the world did not end.

Of course the fear language directed to the public 'planes falling from the sky', autos stop working, bank balances evaporating... all this was total crap.

bigTom: I don't think people are enamored of R0 as much as looking for some indication of the biology of this virus. From a public health point of view, R0 and CFR have meaning but they also have limitations. The same is true of all population measures since they aggregate individuals. We not only talk about incidence rates but age and cause specific incidence rates. So your comments about R0 apply to many things.

jay: You make a valid point. I even thought about it while I was writing it. The basic philosophical issue is about causation and counterfactuals: we don't know what would have happened in either case if we had done something else. Considered as a one-off experiment this is not an easily solved problem (although there is a small cottage industry amongst philosophers of science regarding counterfactuals and causation). In the practical case we interpret the data with the help of ancillary data which we hope cross links with what we see and is consistent with it (philosopher Susan Haack uses the metaphor of a cross-word puzzle). So, yes, from either a logical or metaphysical point of view we don't know what would happen if we didn't try to interrupt transmission. From a public health point of view, however, it is a game theory problem: what are the gains and losses for the various outcomes. I could have put it that way but it would have obscured another point I was trying to make: that the decisions made by public health authorities were neither irrational hysteria nor inconsistent with a precautionary approach and they would be blamed whatever they did.

TomDVM: I'm not particularly sensitive about your constant ragging on epidemiology and epidemiologists, but it is getting a bit old after all these years. And let's face it, veterinarians have conspired to put us into this fix with their enabling of industrial farming. Glass houses and all.

Jay,

We wouldn't have known if the Y2K thing was a problem or not until we looked. Many realtime systems did not use time in any of their calculations, but only for reporting purposes - these were immune from Y2K, except for some amusing reports. However a lot of billing and payroll software was affected (and if you think that doesn't count, just try to short an employee a couple of dollars). Some 2 digit year Cobol programs calculated really problematic interest rates.

Expect the same problems whenever any variable can roll over because it is not large enough.

Tom,

You know how the swine industry is important to Quebec. You certainly know how much infections in swines we had in Canada in the last 10 years and how much environmental problems it has created, Despite all this I have worked very narroly with the Quebec Agricultural Union in Rural Regions via a huge and powerfull organisation calle Rural Solidarity of Quebec.

This event, is sad, it will mainly hurt small and medium farmers who have borrowed money that they will NOT be able to cope with. It will have a rural social impact and certainly families and villages tragedy.

I have visited so many times swine rural farms, I know the conditions of the farmers, the animals and environmental problems. As they say in many Cultures, ''it was written'', it is indeed tragic but it was foreseeable.

Now, for those of us who are solidaire to farmers a lot of work is on the table, as if there was not enough already.

I understand your frustration but there are well over 10 years of objective facts about the virals problems of swines, provbably due to their biological sensibilities.

We must first, IMHO, do what we can to reduce morbidity and mortality among Humans.

Snowy

Revere.

Funny thing is that I don't see or hear many good epidemiologists saying anything about the bad epidemiologists...kind of like good government regulators staying silent about the bad ones.

Industrial farming is controlled by industry...not farmers or veterinarians.

Epidemiolgists in the past twenty-seven years have been mining those same industrialists...or maybe industrialists are mining the epidemiologists.

If you have a complaint about a veterinarian, complain. We are after all strictly regulated.

If I have a claim about an epidemioligist, where do I complain.

The 35,000 figure just the latest example of these screening studies...garbage in-garbage out...and everyone suffers as a result...over and over and over again.

Given that the strain is a mild one, wouldn't it be best if we did not try to constrain it's spread, which has severe negative consequences, and let the virus do what the flu virus does?.

One of the lessons from 1918 was that those who were infected when the flu was going through it's mild phase in spring, did better when the second more severe wave came in the fall since they had a natural immunity.

It was only during the deadlier wave that limiting social contact proved to be beneficial in slowing the spread. However, this did not eradicate it, the flu kept reappearing for several years, and after a while, most everyone had some immunity to it and it went away, or evolved to a strain that was not as deadly and became seasonal.

There is no guarantee this flu will increase it's virulence, and since it's already endemic in Mexico, there is no way to eradicate the virus given our lack of understanding of influenza.

Yet today you have people with mild respiratory illnesses flooding emergency rooms. How many people with serious illness are having treatment delayed, deadly for those with certain illnesses.

This over-reaction is a shame. When the next pandemic alert is sounded, it may be met with yawns, even if the next one is the real deal and should be taken seriously.

Jay,

We wouldn't have known if the Y2K thing was a problem or not until we looked. Many realtime systems did not use time in any of their calculations, but only for reporting purposes - these were immune from Y2K, except for some amusing reports. However a lot of billing and payroll software was affected (and if you think that doesn't count, just try to short an employee a couple of dollars). Some 2 digit year Cobol programs calculated really problematic interest rates.

Expect the same problems whenever any variable can roll over because it is not large enough.

GeorgeT: With respect to your hospitalization rate estimates, I can only conjecture that are confusing probabilities with percentages.

From Molinari et al (2007) The annual impact of seasonal influenza in the US: measuring disease burden and costs.
http://www.ncbi.nlm.nih.gov/pubmed/17544181

Pr(hospitalization/flu infection)

Age ---> Probability
0â4 -----> 0.0141
5â17 ----> 0.0006
18â49 ---> 0.0042
50â64 ---> 0.0193
65+ -----> 0.0421

Note that the numbers listed above are probabilities, not percentages.

-Crow

The overreaction or the overreaction to the overreaction is quite a conundrum. I hope people are being smart, but I think some folks can only maintain a heightened state of alert for so long before they actually get fatigued. I know I've gotten tired over the last week from observing, worrying and washing.

Of course all of your super scientific talk is a little over my head, but I thought this was an interesting part of an AP article:

"Getting fast and effective care is important, said Hugo Lopez-Gatell Ramirez, deputy director general of epidemiology at the center. Among the 16 confirmed swine flu deaths in Mexico, the average time victims waited before going to a doctor was seven days. For those who were sickened but recovered, the average wait was three days."

You can find the full article here:http://www.google.com/hostednews/ap/article/ALeqM5gzz357patY4-QaJFvo9O9….

TomDVM: You clearly don't know what epidemiologists say about each other or you wouldn't have said what you said. Marvin Schneiderman, the late chief statistician for the National Cancer Institute, once said that epidemiology was the practice of criticizing other epidemiologists. We do that incessantly for reasons having to do with our science. I was not trying to impugn all veterinarians or veterinary science, but merely pointing out to you that there is plenty to criticize in veterinary practice, including making general scientific statements about clinical practice without testing them scientifically, as per your notion of prednisolone espousal for avian flu.

As far as whom to complain to, about what? If I think many veterinarians have sold their souls to agribusiness, to whom do I complain? Your profession doesn't regulate that. You enable it,. Just sayin'.

Feel free to have the last word on this. I don't think it is very productive and I won't be responding on this topic. Of course you are welcome to comment, as always, whether on this or anything else. While I often disagree, I am glad to have you speak your piece.

pft: "Mild" is a relative term. If this virus "had its way" it could produce many sick people with a miserable illness and many deaths, just as flu always does. So far it is not a killer virus like H5N1, but that's kind of a high bar.

Interesting developments on the WHO page. They listed the laboratories worldwide that are deemed competent to test. US has only 3 (NY, Atlanta, Memphis). They also provided a request form for institutions to order the primers.
http://www.who.int/en/ However, the only people likely to get tested are those who are deemed to sick to stay at home.

"When the next pandemic alert is sounded, it may be met with yawns, even if the next one is the real deal and should be taken seriously."

As former reporter, I can pretty much guarantee you that if this flu returns in the fall and it packs a wallop, a whole lot of people are going to sit up and take notice really fast! It may take a few days or a week to get folks to restock their cupboards and fill up their gas tanks, wash their hands and cover their mouths, but if confirmed flu deaths in America hit the headlines and even three bodies pile up, it will be everything the President, scientific community, and press can do to prevent a store-emptying, stockpiling, hoarding panic.

And just to revisit an earlier post about whether Revere(s) are necessary... Considering the number of folks out there distorting the facts and understandings of this virus, either with hyperbole or utter complacency, I say every voice of reason is needed! Keep on keeping on, Revere(s)!

The question is, is it really worth it to the average person to have schools, businesses etc. shut down, especially in areas where there is little or no transmission? It seems pretty extreme to me. I mean, to an average healthy person, especially someone who is an hourly worker and needs every bit of money, this might be a bigger inconvenience than getting the flu, if it's really as low a risk as seasonal flu...

Why don't the authorities just take the really serious measures like closing things for populations which are at risk (i.e. retirement community/nursing home areas etc.) ?

sff: The reason is that everyone is at risk from this virus, because there is no natural immunity (although there is some question about cross reactivity from previous H1N1 exposure in those of us born before 1957. So the usual "ar risk" categories don't apply. Widespread "normal" flu would be a serious community health problem, presenting a substantial burden of illness, absenteeism and fatality. Our current medical care system would buckle under the load. The strong measures that seem excessive to you are the ones that might interrupt transmission enough to allow the virus to peter out during the usual summer flu hiatus and buy time to prepare for its return next flu season. It's a gamble but in the estimation of flu and public health experts worth the investment since the pay off is great and the down side risks even greater.

Life is full of trade-offs and uncertainty. This is the best, most rational approach to the plausible scenarios.

revere,
You write,
"When I say prepare, I am not just talking about a vaccine, although that will be an important, but difficult part."
I may be unaware of cutting edge techniques but surely this will be IMPOSSIBLE, not just difficult, to prepare in advance.
So why not mention antivirals?
How about a call to facilitate the fast-tracking of all drug candidates considered possible treatment for influenza. Expansion of drug delivery options. How many people are even aware of the potential of iv peramivir, iv zanamivir, A-315675, CS-8958? Their ability to plug the holes caused by Tamiflu resistance?
I realise the thrust of the article is the "need to invest urgently in health care, public health and social infrastructure", so perhaps you were saving antivirals for their own article, I hope I haven't spoilt the surprise.

miso: I was going to do a separate antiviral post and probably will, but it got pushed out by another issue, people to pigs (probably tomorrow afternoon). However in my estimation antivirals are a marginal issue, since they depend on a functioning health services system and an adequate supply and distribution network and they are not that effective. I am more concerned with the institutional and community response which will be desperately needed. I also put talking about antivirals that are not on the market lower on my priority scale. I realize it is your main interest. There are a lot of people whose interests don't exactly coincide with ours, I am sure. We do what we think is best by our lights. Feel free to disagree.

Crow: Thanks. I didn't confuse. Those NIH numbers you came up are very different than the CDC numbers - they got their numbers from different sources. The University of Utah paper I read stated that infants were hospitalized at a higher rate for the flue than the elderly but the NIH numbers do not bear that out. So we have three somewhat conflicting sets of data. Maybe the way they count cases is different.

But it is interesting to see that adults are hospitalized more often than 5-17 which would explain a LOT (I have theories about that but won't go into that tangent here). If we go with the numbers from NIH, the swine flu hospitalization rate is close to normal for a seasonal flu given that I suspect there is a stronger bias towards hospitalization at the moment.

River: I hope you are right.

Sff: Most people are only looking the economic cost of closing schools, etc. I guess I need to give a Risk Management 101 here. Let's set aside the moral, ethical, and health considerations and just focus on the money.

You look at the cost of closing the schools to the economy. Then you look at possible scenarios of not closing and each one calculate the cost and the probability of each event. Multiply the cost by the probability of each one and sum them up. Take whichever number is less and that is the option you should pick.

Now in real life, you have to factor in all those items I set aside at the beginning. Plus there are a ton more - if a child dies because they didn't close schools the exact same person who are whining now would be the first ones to sue the schools for not closing.

You actually hit upon this whole risk management angle in saying "if it's really as low". That's what nobody knows. Let's say we assign a 80% probability to that, a 5% probability to a repeat of 1918, and a 15% to something in between if schools didn't close. If you run the math, I think you would find that closing the schools is the right economic decision. And the non-economic factors would back up that decision.

sff: revere and I are making the same point and were posting in parallel. Basically, I expanded upon his statement "It's a gamble but in the estimation of flu and public health experts worth the investment since the pay off is great and the down side risks even greater."

Transparency

Extremely important. Daily news briefings indicating "new cases" is demanded by media: if these don't happen: something to hide.

BUT: "new" confirmed cases does not necessarily imply spread, but backlog of lab results.

How do we explain this convincingly [media assumes I have s/thing to hide]? That's my challenge.

And I'm not a media type, just the local boffin who's expected to have all the answers.

Any advice, people?

Jay Gordon said: "That would have mitigated some of the panic and allowed for a calmer discussion."

This cannot possibly be the real Jay Gordon. This is the precise opposite of what the real Jay Gordon encourages with autism.

"and they are not that effective."

Revere,
antivirals are as effective as the regulatory authorities require them to be. Tamiflu was effective as a world without H5N1 and H1N1/2009 needed it to be.

Please use zanamivir as your bench mark and tell me how ineffective it is. Ignore the inhaler, that's just GSKs way of punishing the world for falling in love with Tamiflu instead.

Imagine a zanamivir injectable and tell me how it is ineffective.

Then tell me the good reason why the SEAICRN has taken four years planning iv zanamivir trials on H5N1 victims and still hasn't injected trial candidate one.

â⦠and there is clear and convincing evidence of person to person transmission â¦â

Careful much? There seems to be overwhelming evidence of person to person transmission. In Germany a nurse who treated a swine flu patient and a man who was with him in the hospital room (that was before they knew that it was swine flu) got sick. Seems unlikely that there was any other cause than person to person transmission.

Is it not concerning how many health care workers have caught the virus or is that par for a flu virus?

The M.D. in Mexico who spoke about the death of his two interns said that many, many healthcare workers had caught it. Also, the nurse in Germany caught it, and the doctor in Washington state as well. Is that an abnormally high transmission rate?

One of the overreaction fears I have is that even if this thing ends up being very mild, press coverage of (some of) the individual tragedies may generate a sort of hyper-fear reaction in some people. We now have a nation, which has to drive kids to school because of a hugely distorted fear of the risk from sexual predators. Are we going to become a nation afraid of person to person contact, because of sensationalist coverage of an epidemic? It is hard for me to imagine how we could avoid that fate.

Michael: Taking revere's statement out of context like that makes it sound like hedging, but you read the original in the context, it absolutely wasn't.

"Given that the strain is a mild one, wouldn't it be best if we did not try to constrain it's spread, which has severe negative consequences, and let the virus do what the flu virus does?."

If we had reason to think it's odds of mutating more deadly are the same as a typical flu, it is a valid question whether to sacrifice some 3rd world lives for 1st world economic output (which funds foreign aid and 3rd world economies). It might mutate.

"One of the lessons from 1918 was that those who were infected when the flu was going through it's mild phase in spring, did better when the second more severe wave came in the fall since they had a natural immunity. "

I'm personally not aware this has been demonstrated let alone data exists to interpolate your conclusion. Plz prove me wrong and back this up. To my knowledge, 1919 data is scarce; the world was so weary.

"It was only during the deadlier wave that limiting social contact proved to be beneficial in slowing the spread. However, this did not eradicate it, the flu kept reappearing for several years, and after a while, most everyone had some immunity to it and it went away, or evolved to a strain that was not as deadly and became seasonal."

Today Health Canada just found the phenotypes of the "transmissibility" parts of the flu (unsettling they can do this and so quickly). It has just barely a high enough R0 (gimme a break it is two symbols long I don't care if I'm using it wrong) to keep itself going. So if CDC would've reacted to Veratect's early warning (strange if the CDC won't pay attention to these that they don't pay someone else to watch their emails or subsidize someone too poor to subscribe to Veratect, to do this), there might've been a chance to isolate it in Mexico. So...the opposite of what you are saying.
Pft is an appropriate designation. Pfffft

"We do what we think is best by our lights."

Your right. I tried to contribute to demand for alternate antivirals, for Relenza, to perhaps force GSK to open another production plant. Futile at the time. Too late now.

Given your priorities, low on antivirals and vaccines, might I suggest preparing for a plausible near future event with bulldozers and bags of lime.

As a case study example, here is the WaPo account of the Federal Agent, Griswold, who traveled to Mexico w/ Obama, which highlights the problems w/ false negatives in testing as well as the unorganized response by the school, health department, and random comments by the governor, http://www.washingtonpost.com/wp-dyn/content/article/2009/04/30/AR20090…

"When he got home, he chalked up the cough to Mexico's pollution and thought nothing of it the night after his return when he brought a present from Mexico to his brother's house and stayed for dinner.

Griswold's wife, Alison, a registered nurse, was the first to notice something wrong in the family. When she checked on her 7-year-old son at school April 21, something about him seemed off. He said he felt fine and he looked all right, Alison Griswold said. But the school nurse said he had a low fever, so Alison took him home and kept him there for two days until he recovered.

Then she started getting sick: a cough, a high fever and chills. Last Friday, Griswold and his wife went to a doctor, who wasn't overly concerned. On Sunday, they saw another doctor, who gave them a flu test that came back negative. On Tuesday, on advice from health officials, the couple and their youngest child got the more thorough nasal swab test.

The results came in Wednesday morning: positive for Type A influenza, probably the swine flu."

"Meanwhile, at home, Griswold and his wife tried to help their children get back into school. It was only at the advice of health officials that they kept their two unaffected children at school and sent the sick one back Wednesday, they said."

The sick child's elementary school was notified late Wednesday, 4/29...

"Folger McKinsey was scrubbed with disinfectant last night, and health authorities told school officials that it was safe for it to be open today." (Thursday, 4/30)

From 5/1 WaPo
"Gov. Martin O'Malley (D) and state health officials said there was no need to cancel school because the infected students had not been in school since last Friday -- a span of time beyond the suspected incubation period -- and because they could tie each case to a relative who had been to Mexico, where the disease is believed to have originated."

From Sat, 5/2 WaPo
"Anne Arundel officials announced closure of Folger McKinsey Elementary in Severna Park for at least a week because of a likely flu case in the family of an Obama administration security worker, probably infected during an official trip to Mexico. The closure alarmed parents, who had been told that the ill family members were recovering. As it turned out, that had not changed. School officials were simply following direction from the federal Centers for Disease Control and Prevention. In a conference call with governors of all 50 states yesterday, the CDC said any school with possible cases should be closed."

According to WaPo, Griswold was recovered and back at work on Friday, 5/1, and I still don't think CDC has officially "confirmed" him, though.

Phillip Huggan

"If we had reason to think it's odds of mutating more deadly are the same as a typical flu, it is a valid question whether to sacrifice some 3rd world lives for 1st world economic output (which funds foreign aid and 3rd world economies). It might mutate."

We might be invaded by UFO's, maybe we already were. Should we start doing DNA testing on everyone to root out the aliens? In 1976 we were told the Swine Flu would cause a pandemic. Forty million people were vaccinated, and 35 died from the vaccine, none from the flu. The science is just not there in knowing how a virus will mutate. It has just as much chance of mutating itself out of existence.

"I'm personally not aware this has been demonstrated [immunity from 21nd wave if infected in first wave]let alone data exists to interpolate your conclusion. Plz prove me wrong and back this up. To my knowledge, 1919 data is scarce; the world was so weary."

There is anecdotal data in the literature and newspaper articles from the time, plus we are told that those infected during the last H1N1 pandemic in 1957 may have partial immunity to this one, it's not a new concept.

In "The Great Influenza" by John Barry on page 373, it says "People who had gotten sick in the second wave had a fair amount of immunity to another attack. Just as people sickened in the first wave had fared better than others in the second wave".

"Today Health Canada just found the phenotypes of the "transmissibility" parts of the flu (unsettling they can do this and so quickly)...... to keep itself going. So if CDC would've reacted to Veratect's early warning (strange if the CDC won't pay attention to these that they don't pay someone else to watch their emails or subsidize someone too poor to subscribe to Veratect, to do this), there might've been a chance to isolate it in Mexico. So...the opposite of what you are saying. Pft is an appropriate designation. Pfffft"

Ok, so you may have isolated it to Mexico using draconian measures, and I doubt CDC has the authority to act in Mexico. What does that mean? Nobody knows the origins of the virus, or if it even came from Mexico, do they. Just like nobody knows for sure where seasonal flu lurks each summer before coming back to bite people in the fall/winter.
But you suggest we should have closed borders and isolated Mexico, maybe even stopping birds from flying North, for a mild flu which has killed 100 people globally?

Good scientists recognize and deal with uncertainty, and do not pretend to a certainty that does not exist. Yet there are those pseudo scientists who cooperate with a political agenda, such as Climate Change, and they pretend to a certainty that does not exist, when all they have are unproven and untested hypotheis that are just as likely to be false as true.

Acting in the face of ignorance can have unintended consequences. This virus should certainly be monitored, but acting to control it's progress may have unintended "negative" consequences, and also a lost opportunity to see how a mild new virus progresses globally (this is secondary of course).

Vaccines can still be prepared. Tamiflu can still be stockpiled. Preparations for a real pandemic can proceed. But stuff like quarantining a hotel in Hong Kong, border closures, and using Tamiflu for mild flu which is sure to promote resistance should the virus turn more virulent is sheer lunancy, if not criminal.

Revere,
Regarding your comment to Tom DVM:

"...veterinarians have conspired to put us into this fix with their enabling of industrial farming"

If we're going down this road, perhaps we should indict the entire land grant college system of the US that has conspired with big business to make our agricultural system the petroleum addicted, speed obsessed, disease fostering, environmentally suspect industry it is today. My second indictment: the American consumer who continually chooses cheap over wholesome, environmentally benign food and demands it 24/365. My third indictment: the American political system that embraced a cheap food policy early in the last century and continues to do so to this day.

Why don't you blame yourself? You banged the alarm drum on avian flu and people are catching on that that was nonsense. Then you banged the drum on swine flu, and people are catching on and will catch on. If a real monster DOES come along, and it certainly may, it is the alarmists who will be at fault if people decide it's just another false alarm.

To George T. Re: crap on the internet. I stand corrected after following your links. Yikes.

Fumento, it's not a 'false alarm'.

The situation in the media is the result of the nature of the available information, which has changed as time progresses.

Epidemiology isn't something where you can sit on the data and wait to confirm something is dangerous before you try to put a cage around it.

The early data showed this was a new virus with unknown severity, and that it was transmitting readily between humans. How should health authorities react to such news?

They could do nothing, and wait to see if it is a dangerous virus or not. But since it is already transmitting between humans, if they do that and it *does* turn out be be dangerous, then the virus would have a huge head-start in the population, and be impossible to contain in any meaningful way. What is more, that head start corresponds to that many more folk sick or dead before a vaccine becomes available in meaningful quantities.

Or, they could enact measures *as if* they knew the virus was dangerous. This is expensive, inconvenient, and can cause panic, and it is what was done in this case. It requires telling people who have little training and therefore little judgment in such matters, that there might be a monster killer rabbit with big sharp teeth scratching the door and so we need to guard it--but it also just might be a rabbit. We don't yet know which but we need to take monster precautions until we find out.

In *either* scenario it is an 'emergency' for public health in the sense that politicians and healthcare workers need to gear up for possible battle regardless of whether the threat is severe or mild.

Now, it turns out in this case to have just been a rabbit, not the killer rabbit of 'Monty Python and the Holy Grail' fame. But you can't tell just by first sight.

And, from a healthcare provider prospective, this is *still* an emergency, and not because of the panic of well-people crowding the ERs. Eventually, if this flu continues to spread,though only a tiny fraction of people will need to see a practitioner, so many people will be ill in the outbreak areas that this tiny fraction will *still* swamp doctors offices and hospitals.

So, the illness is generally mild, therefore the risk to individuals who get sick is slight. The average Joe needn't fear if he catches it because it currently appears that it will behave much like the familiar seasonal flu.

But, taken as a whole, since so many in the population will get sick, it is still a resource deployment emergency for people who work in health care. Therefore agencies still need to go into emergency mode. There aren't enough resources deployed to take care of the tiny fraction of a huge number who really will need medical care even if the virus is mild in the general case.

Hence, officials panic. They have a lot of work to do. The press picks up on their panic and conveys it to the public as if the public should be panicked too.

There's always the risk that the virus will do something like its 1918 ancestor, which started off as a mild spring flu then returned the following winter as a killer. But at this point such a path remains speculation.

You notice we talk about having resources positioned to deal with a killer mutation if it happens, but nobody is particularly running around banging a drum to make the public worry about it. Why? Because it remains speculation, and the measures they must take against a potentially severe virus are the same ones that we're asking them to take for what turned out to be a mild one. If they're already hand-washing and social-distancing, that should slow the flu *regardless* of its severity, making questions of its severity irrelevant.

The alarm on avian flu wasn't, and isn't, nonsense. The press just got tired of it because H5N1 hasn't 'gone pandemic' in a short time-frame. As long as H5N1 keeps infecting people with high lethality, it remains a potential threat that must be watched, tracked, and planned against. Just in case.

An ancillary issue that both these viruses bring to life is that of factory farming and what role current practices play in launching new viruses. If you'd like a problem worthy of a lawyer to look at regarding flu, I suggest tracking down what's going on with factory farming practices and whether there are economically viable alterations that can make those facilities biologically safer.

Lisa and others: Fumento is a notorious troll. Don't feed him.

"The science is just not there in knowing how a virus will mutate. It has just as much chance of mutating itself out of existence."

Love your 50% odds. I'll say in the absence of wiping out all reservoirs or pig vaccines or this epidemic petering out among human populations (yesterdays phenotyping analysis suggests social distancing like in Mexico might do just this; is barely spreading now) with or without social distancing measures; I'll say 13% odds of a second wave. If what I read is accurate that Spanish Flu was the generally more deadly Avian and this is relatively milder Swine, I'll say 1% mortality in developing world and 0.25% 1st world.

"Ok, so you may have isolated it to Mexico using draconian measures, and I doubt CDC has the authority to act in Mexico"

WHO's Rapid Response blueprint is a suggestion for sovereign national health agencies. I can't imagine any nation on Earth, even those who's healthcare infrastructures have been Iraq-ed by Americans, not taking the advice. I'm not suggesting a personal blueprint here, I'm reporting WHO living guidelines circa 2007.

"Nobody knows the origins of the virus, or if it even came from Mexico, do they."

The evidence strongly suggests it. Probability isn't a coin flip. The cluster of Mexican cases alone suggests Mexican origin. Maybe 20-75% with some uncertainty. You assume because the uncertainty is 25-80%, that it must be 100% and every situation that has the tiniest degree of uncertainty renders the choice 50-50. There was a Daily Show skit on this last week I wished you would've watched.

Revere said, "I was not trying to impugn all veterinarians or veterinary science, but merely pointing out to you that there is plenty to criticize in veterinary practice, including making general scientific statements about clinical practice without testing them scientifically, as per your notion of prednisolone espousal for avian flu."

Over two years ago I published a paper in J Med Microbiol on the rationale for using steroids in H5N1. I wasn't enthusiastic for using it then, and I am totally against it now, having conducted much literature and theoretical research in the field of burns/sepsis/shock, which we will publish this June in a book on pediatric burns.

Marissa

"You notice we talk about having resources positioned to deal with a killer mutation if it happens, but nobody is particularly running around banging a drum to make the public worry about it. Why? Because it remains speculation, and the measures they must take against a potentially severe virus are the same ones that we're asking them to take for what turned out to be a mild one"

No, we don't have those resources. Nations like Burma and China cover up pandemics and CDC ignored Veratect's multiple early warnings. Many 3rd world hospitals probably don't have electricity for fridges. gelFAST (and any pager-like alcohol rub dispensor competitors like Sprixx) is stuck in an absurdly long trial to "prove" when doctors and nurses sanitize their hands, disease rates go down. Doctors in borderline 3rd world nations are in the same boat as me: too poor to afford scientific papers in the midst of an epidemic and too rich to qualify for freebie handouts.
I guarantee if pigs infected with this strain; if the strain demonstrates rapid mutation capability the scenarios would be much more severe; personally you'd soon be ask to double or triple shift.

Last Sunday, I pictured myself as Mel Gibson in "We Were Soldiers" looking around at the battlefield to see if about to be completely over-run. Despite P.Revere and everyone else's warnings to the contrary that we didn't know how fast this was spreading, I didn't see it; Swine Flu was not spreading fast (and it turns out, not that deadly among non-pneuminia at-risk populations). If this was Spanish Flu 3rd wave the world would immediately go into Great Depression and a variety of economic sectors would cease to exist.

"...there is plenty to criticize in veterinary practice, including making general scientific statements about clinical practice without testing them scientifically, as per your notion of prednisolone espousal for avian flu."

Revere

Since you raised the issue of prednisolone again, I thought I would include some links to indicate to you that it is not just myself or veterinarians that are in favour of treating ARDS with prednisolone...

...and I would add..just because it has not worked when used with protocols developed during SARS...that it would not be completely appropriate and ethical to use it in other dosages as I have explained to you in the past.

I think we should explore every possible tool with the potential to be used in an H5N1 pandemic with a CFR above 25%...especially those medications that could be dispensed like oral-statins and oral-prednisolones...

...don't you?

1) Methylprednisolone Infusion in Early Ards - Results of a Randomized Controlled Trial.

http://www.chestjournal.org/content/131/4/954.full.pdf+html

2) Glucocorticoids Just Do It

http://www.chestjournal.org/content/131/4/945.long

.............................................

3) Prolonged glucocorticoid treatment in acute respiratory distress syndrome: Evidence supporting effectiveness and safety.
Meduri GU, Marik PE, Annane D.
PMID: 19373049

________________________

Crit Care Med. 2009 May;37(5):1594-603. Links

Comment in:
Crit Care Med. 2009 May;37(5):1800-3.
Use of corticosteroids in acute lung injury and acute respiratory distress syndrome: a systematic review and meta-analysis.
Tang BM, Craig JC, Eslick GD, Seppelt I, McLean AS.
Department of Intensive Care Medicine, Nepean Hospital, Penrith, New South Wales, Australia. benjamin@clubsalsa.com.au

OBJECTIVE: Controversy remains as to whether low-dose corticosteroids can reduce the mortality and morbidity of acute lung injury (ALI) or the acute respiratory distress syndrome (ARDS) without increasing the risk of adverse reactions. We aimed to evaluate all studies investigating prolonged corticosteroids in low-to-moderate dose in ALI or ARDS. DATA SOURCES: MEDLINE, EMBASE, Current Content, and Cochrane Central Register of Controlled Trials, and bibliographies of retrieved articles. STUDY SELECTION: Randomized controlled trials (RCTs) and observational studies reported in any language that used 0.5-2.5 mg.kg.d of methylprednisolone or equivalent to treat ALI/ARDS. DATA EXTRACTION: Data were extracted independently by two reviewers and included study design, patient characteristics, interventions, and mortality and morbidity outcomes. DATA SYNTHESIS: Both cohort studies (five studies, n = 307) and RCTs (four trials, n = 341) showed a similar trend toward mortality reduction (RCTs relative risk 0.51, 95% CI 0.24-1.09; p = 0.08; cohort studies relative risk 0.66, 95% CI 0.43-1.02; p = 0.06). The overall relative risk was 0.62 (95% CI 0.43-0.91; p = 0.01). There was also improvement in length of ventilation-free days, length of intensive care unit stay, Multiple Organ Dysfunction Syndrome Score, Lung Injury Scores, and improvement in Pao2/Fio2. There was no increase in infection, neuromyopathy, or any major complications. There was significant heterogeneity in the pooled studies. Subgroup and meta-regression analyses showed that heterogeneity had minimal effect on treatment efficacy; however, these findings were limited by the small number of studies used in the analyses. CONCLUSION: The use of low-dose corticosteroids was associated with improved mortality and morbidity outcomes without increased adverse reactions. The consistency of results in both study designs and all outcomes suggests that they are an effective treatment for ALI or ARDS. The mortality benefits in early ARDS should be confirmed by an adequately powered randomized trial.

PMID: 19325471

Thanks as always to the best researcher that I have ever met...Beehiver.

Here is another link to the first Chest article in case anyone has a problem.

http://www.ards.org/EARDS-CS-Chest-07.pdf

Tom,

exerpt from our book chapter:
Recently, the largest RCT (randomized controlled trial) to date of hydrocortisone therapy in patients with septic shock was published (N = 499).77 The results appeared to completely contradict the assertion of Annane et al76 that low doses of glucocorticoids were beneficial, since the trial utilized 200 mg/day of hydrocortisone in the treatment arm, and found no statistical difference between treatment and control groups with regard to survival or reversal of shock. To say that clinicians find themselves in a quandary regarding these latest developments would be an understatement, but perhaps further analysis regarding the use of glucocorticoids may place the results in context.
The total number of patients in the original meta-analysis76 was 465, but the N of the new RCT was 499, which means that a new meta-analysis incorporating these results would weight the trial at 43% (Figure 1). Note that the new RR of 0.83 and NNT of 8.6 are similar to the values for the old meta-analysis, indicating little or no change in the effect size. However, the larger total has changed the precision with a new 95% CI of 0.65 to 1.09. Therefore, the result is no longer significant, suggesting the evidence for steroid use in sepsis/shock is equivocal.
This result is not surprising and should be a salutary lesson to all clinicians who accept meta-analyses at face value. The clue lies in the confidence intervals in the original Annane et al meta-analysis,76 the upper limit of which is 0.95ânot far from 0. Any small shift in this value upward would likely have caused it to cross the â0â line, which is no longer statistically significant. In other words, the analysis should have been greeted with much caution rather than interpreted as a âgreen lightâ to treat patients with glucocorticoids. Another important point that is rarely discussed are the actual risks and benefits to patients in the context of the NNT value.78 For example, not all patients will face the same risks of mortality for a given sepsis/shock situation, and assessment of a patientâs risk and possible benefit derived from steroid treatment must be weighed against the NNT value. For example, if the risk of mortality were substantially less than 10%, then giving glucocorticoids might actually increase the patientâs risk of dying.

Refs
76.Annane D, Bellisant E, Bollaert PE, Briegel J, Keh D, Kupfer Y. Corticosteroids for severe sepsis and septic shock: a systematic review and meta-analysis. BMJ 2004;329:480.
77.Sprung CL, Annane D, Keh D, et al. Hydrocortisone therapy for patients with septic shock. New Engl J Med 2008;358:111-124.
78.Furukawa TA, Guyatt GH, Griffith LE. Can we individualize the ânumber needed to treatâ? An empirical study of summary effect measures in meta-analyses. Int J Epidemiol 2002;31:72-76.

Thanks Marissa

In you opinion then are glucocorticoids contraindicated in all acute atypical pneumonia's...

...and if so, then how would you treat those who die from primary viraemias in the first 24-48 hours?

...by the way...200 mg. daily seems excessive.

DUMB QUESTION RE: CYTOKINE STORM AND ANTIHISTAMINES
Is there any chance, or research on, whether large doses of an antihistamine (such as Benedrylâ¢) might have any effect on a cytokine storm type reaction to a flu of the 1918 variety?

"It requires telling people who have little training and therefore little judgment in such matters, that there might be a monster killer rabbit with big sharp teeth scratching the door and so we need to guard it--but it also just might be a rabbit."

As well as that (because of the rapid mutation of the virus) the bunny, why initially nice, might mutate into a monster killer bunny with big sharp teeth.

And yes, Fumento is a troll, who thinks 'cos he interviewed Pete Palese once that he's become a flu expert by osmosis.

Tom,

I think what you have to do is separate out the few genuine cases of adrenal insufficiency (which is hard; maybe treat those carefully with replacement steroid levels) and then lower the cases in which cortisol levels are exceptionally high (adrenals working overtime); the pilot method used in burns cases where this is not uncommon for high TSBA cases is to use ketaconazole.

John, as far as I know, those kinds of drugs mostly affect the histamine response not the other cytokine cascades.

Hi Marissa

Thanks.

See the thing I don't get is that when prednisolone is given in moderate dosages intramuscularly or subcutaneously, with a double loading dosage and removed by five days or seven at the very latest...the drug is harmless...

...it does no harm and it mimic's the bodies natural response to infection...it just reinforces it and definitely prevents the immune system's overwhelming response to initial infection loads.

There is no immunosuppression...and if there was, it would not be used in auto-immune reactions to in my case a rabies vaccine and in a colleagues case, to canine ringworm in his facial hair.

So it really don't get this controversy.

If the drug is used in larger dosages (then say 200mg) then there is a law of diminishing returns even in the short term...why there seems to be this threshold, I have no idea.

Secondly, I would try very hard to have the drug removed by five days and the patient being maintained on non-steroidal anti-inflammatories...and I don't think in this shortterm moderate treatment, there is any requiring to lower dosages gradually.

If the treatment is carried on beyond seven days...then you do geet immunosuppression and a linear dimminishing return.

I have found that the steroid (prednisone or other formats don't work-at all) simply buys you time...if the first injection has no affect, then you are out of luck...but if you get a reasonable response then you have a very good chance with supportive therapies.

The treatment must be given early before things get totally out of hand...and that is the point I think in the first reference.

Without it, I think in the coming H5N1 influenced pandemic, we will have written-off about 15% of those affected.

The bottom line is that in a pandemic where you can safely assure that a person is infected, you can treat early because moderate dosages for short periods..do no harm...in my opinion.

I would appreciate any further comments you might have.

I just don't understand the controversy with this wonderful drug.

MNarissa.

I also found that intravenous treatments don't work at all because you get a very high spike and then a crash...you cannot maintain level blood concentrations.

Secondly, I can't believe it doesn't have a role in bacterial infetions where toxins from dead stuff is very similar I think to the dead stuff from pandemic viruses and sometimes seasonal influenza's that trigger the immune over-reaction.

In other animals it works quite well when used carefully... as no treatment is a panacea.

Thanks again

Andrew,

Re: How to feed the media horde.

Being a media hordite, I can only recommend speaking slowly and carefully - and thinking before you speak. Some of us are trying very hard to tell the public what they should know about public health issues. Others, regretably, are in it for the ratings. I know enough about viral infections to admit that I know very little about viral infections -- but I'm not too shy to ask for help. Some of my compatriots are not so aware.

I've used the CDC's 36,000-deaths-per-year-from flu figure -- but I did not know about the NIH study referenced above. If the CDC figure is inaccurate, whether based on erroneous or misinterpreted data, then it should be corrected. But how do I know? (Other than meticulously reading ScienceBlogs.) Do I wish I'd paid more attention in my hard sciences classes? Absolutely. Do I wish I'd taken more math classes? Of course. Do I appreciate a scientist taking time to patiently explain to the old guy with the notebook what data indicates? Oh, please: More.

Most reporters, I think, really want to learn more about science, especially if we're writing/blogging/ about public health issues that, if inaccurately reported, can lead to a panic. (Well, more than public health issues, but we're talking about the flu: Climate change is another morass.)Yet, a reporter's experience skews his/her perception of the public's ability to rationally process information. We are most of us cynics, and we are most of us convinced that most cynics are optimists.

Andrew, as for some advice: I can't remember who first said this, but there are three basic responses which, if given honestly, are appropriate to any question: 1) "I know, and I can tell you." 2) "I know, and I can't tell you." 3)"I don't know." If you must use response two or three, it's helpful if you can add, "but I'll tell someone who can."

I don't always assume that a person who can't/won't respond does in fact "have something to hide." Problem is, it has happened often enough -- and not, I must stress, with scientists -- that any evasiveness at all tends to increase my suspicions.

Parenthetically, NEVER assume that a statement is "off the record." At my paper, no source is permitted to go OTR --ever. Taking something OTR means, to our staff, that the information is inaccessible, regardless of what other sources may confirm it -- because how would we have known to ask about it? I will, in rare cases, grudgingly allow "deep background," which means you will be cited as "a senior source" or "someone with extensive knowledge of the issue," but my publisher hates deep background;She believes that if we can't get a statement on the record, with an identifiable source, then we don't really have the information. Receiving information on deep background doesn't prevent me from trying to find another source, however. I am, perhaps, an exception to OTR tradition. Other reporters may accept OTR -- and others will lie to you.

A critical difference here is the way scientists think, compared to the way reporters think -- or have been trained to think. Old habits can be unlearned, but often not easily.

I was lucky enough to find a copy of "Ideas Into Words: Mastering the Craft of Science Writing," by Elise Hancock. It's the best guide to reporting I've found in nearly 40 years -- and not simply for science writing. If any of you encounter a reporter with a curiosity about communicating science issues honestly, factually and thoroughly, please: Treat him/her kindly, and recommend that book.

Some of the posts here are well beyond me. And some of the posts here are extremely helpful to me in understanding what needs to be said and how to say it.

Thanks, all.

Symptom-wise this flu sounds the same as a kind I had in Feb. 2008, so what's the big deal? Nobody even mentioned that horrible flu, and everybody I worked with was catching it. Why the fixation on this flu over that, which statistically has harmed far fewer people?

While few people appear to be making much public use of their course(s) on differential equations, when they do, I think that they tend to make the mistake of comparing apples with oranges, which is spanky, for sure . . .

Specifically, I think it is very important to include cultural differences when one attempts to use historical data to provide insights on likely scenarios . . .

For example, in the influenza epidemic of 1918, one might want to consider the fact that there were no fast-food restaurants, few if any automobiles, no interstate highways, not a lot of rampant adolescent sexy time, few if any airplanes, and for the most part not a lot of global trade . . .

If one wanted something to eat, then this typically involved someone preparing a meal the old-fashioned way in a kitchen, although there were a few restaurants in most places, but since 1918 was just a few decades after the Victorian Era, one might expect that most people continued to be at least a little bit focused on cleanliness and hygiene . . .

In 1918, most people did not travel 50 to 100 miles each day, and they probably did not make excursions to neighboring towns on a daily basis . . .

And so forth and so on . . .

Today, I think that everything is very different, if only because a single infected person working in a high-volume fast-food restaurant has the potential to transmit their infection to hundreds of people in a matter of hours, where all those hundreds of people are quite likely to travel anywhere from 5 to 50 miles in a short time . . .

Certainly, there were various schools in 1918, but most students attended a school in close proximity to their homes and whatever . . .

All I can do is ponder everything, but intuition strongly suggests that if the 1918 influenza occurred today, the numbers probably would be significantly greater and everything would happen more rapidly, even when one considers all the outstanding advancements in medicine and everything else . . .

So, for the most part, I am focusing solely on the sparse numerical data which is being released every so often by the various governmental bureaucrats, which as of Saturday May 16, 2009 tends to suggest that two weeks ago there were approximately 1,000 reported cases of "swine flu" in the US, but today there are 4,000 reported cases in the US, which if one uses a simple exponential growth rate calculator maps approximately to 70 percent, but so what . . .

Nothing is simple at the dawn of the early 21st century . . .

I find it enlightening that earlier this week the CDC announced that it was abandoning efforts to count the actual number of cases, which tends to be a bit of a clue, especially since one week ago the running total in the US was approximately 1,600 confirmed cases . . .

And for reference, while I made an "A" the third time I took Differential Equations, there are only two things I remember clearly:

(1) The common housefly tracks people by solving differential equations in real-time, which is one of the reasons that you cannot evade them no matter how quickly or randomly you move . . .

AND

(2) When something occurs exponentially, the 60 percent ("Surprise, it's here!") level can be reached very quickly . . .

So, it appears to me that the number of cases has more than doubled since last Saturday, just a week ago . . .

Another useful bit of information is that someone probably has a clue, but the various governmental agencies, bureaucrats, and politicians primarily are focused on maintaining the status quo toward the goal of lessening the impact on those folks who will survive, since first and foremost the our great nation needs to be peopled so that the mega-corporate food industry will be able to sell even more high-fructose corn syrup and other unnatural "food-like" concoctions to ready, willing, and uneducated consumers . . .

Thanks! :-)

So, this morning (Monday May 18, 2009), the CDC reveals there are more than 5,000 confirmed cases of the H1N1 influenza ("swine flu") in the US and that the number of cases in the US probably is more than 100,000 . . .

Based on their being 4,700 confirmed cases on Saturday May 16, 2009--I am very generous in the way I round numbers when doing quick mental arithmetic, which is the reason that I used "4,000" in my previous post, although the article where I got that number might have been updated after I read it--one might guess that it takes a few days to do the laboratory work required to confirm 300 or so cases, which itself is disturbing, really . . .

Is it reasonable to presume that the number of unconfirmed cases is increasing in parallel to the number of confirmed cases?

I have no idea, especially since the CDC appeared to have stopped counting cases sometime last week (at least insofar as the public knows) . . .

And it is spanky that the WHO is having its annual meeting, where one of the topics being discussed is focused apparently on the concerns of various nations regarding the idea of the WHO not providing so much public information at a time when a rapidly spreading disease appears to be a bit mild for some but not all groups of people . . .

Our leaders certainly do not want to discourage people from going shopping at the mall and getting together in as many densely packed public places as possible during an economic recession which looks to make the Great Depression of the 1930s appear to be just a blip in the radar, for sure . . .

While the "swine flu" might appear to be mild in some respects, most of the public advisories I find strongly encourage people with asthma, for example, to contact their doctors immediately or whatever when they notice signs and symptoms that match the signs and symptoms for "swine flu", which I think is an important bit of information when viewed from the patently strange (but nevertheless accurate) perspective noted in my previous post regarding the prudence of considering cultural, societal, and whatever differences when comparing numerical data for epidemics and pandemics, where for example one cannot avoid observing that the number of young people who routinely take asthma medicine likely is geometrically larger today than it was in 1918, if only because there probably was no asthma medicine in 1918, but so what . . .

In the grand scheme of everything, I am relying primarily on the few bits and pieces of mathematics I learned when I was in college and took Calculus I, II, and III, Differential Equations, Advanced Calculus, and Probability and Statistics with Calculus, nearly all of which I forgot soon after each course ended and for the most part have not used since then . . .

Yet, while I would find it difficult, if not impossible, to prove the Pythagorean Theorem or anything else, I have no problem visualizing curl, even though I truly have no idea how to do anything practical with Green's Theorem, and the mirror-image symbol that looks a bit like a horizontally flipped "6", but so what . . .

Doing calculations never made much sense to me, anyway, because I relate to everything visually, in the sense of being able to visualize curl in my mind and to rotate elaborate vector spaces, and so forth and so on, which mostly is the way I was able to pass mathematics courses in college . . .

And while I cannot do much with respect to crunching numbers without resorting to using a computer, I am seeing some disturbing potential outcomes with respect to the "swine flu" epidemic, pandemic, or whatever one wants to call it as I gaze into the future and ponder various values for the cultural and weather condition variables of the various hypotheses, and I certainly have problems with all the public advisories for the most part telling people essentially to "ignore it", because it is precisely during this time that "ignoring it" is completely and totally counter-productive to "containing it" . . .

My advice is to take a two-weeks vacation; to stay inside the house; and to avoid people (especially children and adolescents) whenever possible, based on the general idea that if one never has had measles and there is a global epidemic of measles where everyone on the planet has measles, if you stay inside for two weeks and avoid people, then what little I recall from Biology tends strongly to suggest that you will not contract measles, since if my recollection is correct, communicable diseases do not go very far when they are not communicated . . .

I have no idea . . .

Another thing which is disturbing is the ability of this particular strain or variation of influenza to continue to spread during warmer months, when for the most part, influenza viruses are not supposed to be happy with environmental conditions . . .

The general rule is supposed to be that influenza viruses prefer cool, cold, and wet weather and places--not warm, hot, and dry weather and places . . .

So, what is the deal with the warm, hot, and dry bit?

Is it from the snippets of the viral genetic algorithm (RNA) coming from humans? Or is it the part contributed by birds or pigs?

Is it a coronavirus, retrovirus, ribovirus, or a new hybrid?

I have no idea, but it appears to be a bit unusual for a virus to like warm, hot, and dry weather, really . . .

Thanks!

Baldenario: My usual take on this is that hiding away isn't the way to go. It is time to prepare our communities for whatever might come next (which is maybe nothing) by organizing it to allow people to help each other. Get together with your neighbors to plan for how you might check on each other, get groceries, medicines, etc. That way, if it is you who needs the help there will be someone there and if you are able to help someone you can do that. In 1918 the cities that did the best were the ones who had robust and resilient community structures.

revere: I appreciate what you are suggesting, but my take on it is that the getting together with neighbors and devising a plan for the future aspect is best done before the early stages of an epidemic or pandemic, which is the way Baldenario and his neighbors did it quite some time ago, thereby already having a plan and strategy which maps to a generous supply of N95/P95 respirators, several more advanced respirators with organic/carbon filter canisters, the usual assortment of necessary and potentially useful medicines, plenty of food, water, and so forth and so on, all of which are excellent . . .

It also helps that Baldenario is located in the middle of nowhere along with a few other folks, yet is conveniently near to a hospital with a helicopter pad for ready transport to a regional medical center, should the need arise . . .

From a practical perspective, the primary problem with having a neighborhood get-together this week it that such activities pretty much map to having what some are calling a "measles or chicken pox party", where the general but patently goofy idea is to expose everyone early to a highly communicable disease with the general belief that getting sick sooner is better than getting sick later, which might actually have made a bit of sense half a century ago, at least for measles, mumps, and chicken pox, although perhaps not . . .

Baldenario had measles, mumps (both sides), and chicken pox as a child and needed no vaccines, which certainly was spanky for Baldenario, for sure, although Baldenario was vaccinated against a bunch of other stuff, including being one of the first youngsters to consume a few sugar cubes of polio vaccine . . .

Yet, I think that some combination of our strategies makes good sense, and if one has not formed a plan with a few friends and neighbors--at least in terms of having someone to call and perhaps doing a bit of status-checking every few days--then I certainly agree with your advice, although I think it can be done just as well via telephone calls and emails, since overall the reality is that it is virtually impossible to contract a communicable disease if it never has the opportunity to be communicated to you . . .

Thanks! :-)

This post has nothing to do with statistics.

I had to laugh when I read revere's post "Marvin Schneiderman, the late chief statistician for the National Cancer Institute, once said that epidemiology was the practice of criticizing other epidemiologists." I'm amazed that someone quoted by father in a blog post over twelve years after his death. Also, this sounds just like my father.

Thanks,

Sarah: I knew your dad (and heard him say it). He was a great guy and a great statistician. Lots of us miss him. People like that don't come around every day.