I keep half an eye on the medicine displays in stores when I shop, and this year is the first time I have seen Oscillococcinum being sold. Airborne as been a standard for years, but Airborne has been joined by Oscillococcinum on the shelves. Dumb and dumber. It may be a bad case of confirmation bias, but it seems I am seeing more iocane powder, I mean oscillococcinum, at the stores.
On a recent podcast I was listening to one of the hosts suggested a homeopathic remedy for flu symptoms, and then specifically suggested osillococcinum. This is a technology podcast, the 404, and the hosts are certainly bright, educated people. Why would he suggest osillococcinum? Probably because he unaware of how oh so silly the product is.
Look at the box. Seems impressive. It is non sedating, no drug interactions, no side effects. It also has no cholesterol and no radon. It is, I have heard, the biggest emitter of N-rays ever discovered. It is “officially included in the Homeopathic Pharmacopoeia of the United States”, and we know from yesterdays post how worthless that designation is.
The active ingredient is listed as anas barbarae hepatis et cordis extractum 200C.
Whoa. The power of Latin, like a Harry Potter curse. I bet the product has been imbued with the Confundus charm, which may explain why it is “used by millions of people and is recommended by doctors around the world.”
What is the active ingredient, this anas barbarae hepatis et cordis extractum?
In the 1919 flu epidemic a physician who did not understand that artifacts on the slide, probably bubbles, move randomly due to Brownian motion. Looking at the tissues of flu patients with a microscope, he found what he thought was not only the cause of influenza, but the cause of all diseases: small cocci (round balls) that oscillated under the microscope. He found these wiggling bubbles in all the tissues of all the ill people he examined and thought he discovered the true cause of all disease. Sigh. Yet another cause of all illness. He is the only person, before or since, to see these oscillating cocci. Hence the name.
Subsequently, for obscure reasons, he became of the opinion that the heart and liver of the Muscovy Duck were the most concentrated source of these oscillating cocci. I have found the suggestion that it was because duck liver and heart is a source of influenza, but the product predates the discovery of the influenza, so that would be an oh so silly explanation.
So how best to to treat disease? Turn the oscilliococinum into a homeopathic nostrum:
Into a one litre bottle, a mixture of pancreatic juice and glucose is poured. Next a Canard de Barbarie is decapitated and 35 grams of its liver and 15 grams of its heart are put into the bottle. Why liver? Doctor Roy writes: “The Ancients considered the liver as the seat of suffering, even more important than the heart, which is a very profound insight, because it is on the level of the liver that the pathological modifications of the blood happen, and also there the quality of the energy of our heart muscle changes in a durable manner.”
After 40 days in the sterile bottle, liver and heart autolyse (disintegrate) into a kind of goo, which is then “potentized” with the Korsakov method where the glass containing the remedy is shaken and then just emptied and refilled, and the dilution factor is assumed to be 1:100.
Go to Starbucks tomorrow and get your Americano at 200C made with the same method as oscilliococinum. They will make your drink. Pour it out and fill the cup with water and shake it. Then pour it out, fill it up with water and shake it again. Pour it out etc.. And so on 200 times, the ultimate rinse, lather, repeat. And that should potentize the drink such that you will never sleep again.
By the time they are done, the duck goo can be found at one part duck goo in 102000 water molecules, which is damn impressive since there are only about 1080 (+/- 3) total atoms in the entire observable universe. Then one drop is placed on a bunch of tiny pills and sold for about a dollar a vial in the US. I bitch that linezolid is 50 dollars a pill, but at least there is something useful, 600 mg in fact, in the pill.
And that is the active ingredient. Active. I do not think it means what you think it means. Is here anyone of sound mind who reads the above who thinks oscilliococinum has any potential to treat flu? Really? I have a bridge in Brooklyn I would like to sell you. How this nostrum is supposed to alter the course of influenza is a delusion understood only by homeopaths. Anyone who understands the life cycle of influenza, the immune response to infection would find this concoction mystifying as a treatment for flu or its symptoms.
Oscilliococinum is popular over the world, and many of the testimonials on the interwebs suggest it is effective as both a preventative and a therapy, a stark example of why anecdotes are considered a suboptimal form of evidence.
There is no better example of the disconnect between EBM and SBM than oscilliococinum used for the treatment of flu, since the Cochran reviews have evaluated oscilliococinum and suggests that while it is useless for a prevention, it shortens symptoms by 0.28 days. For reasons I cannot discover, the Cochrane review on homeopathy was withdrawn. Embarrassment would be my guess. Other reviews have found no effect of oscilliococinum on flu symptoms.
Think about it. .28 days is about 6 hours. Have you ever had the flu or other viral illness and could say yes, now, at 3 pm, I am symptom free and no longer ill? Viral illnesses don’t die, they fade away. Given the nature of oscilliococinum, it is far more likely that the 6 hours from the studies was the random variation seen in clinical trials. There is zero reason, based on the known pathophysiology of influenza and the known origin of oscilliococinum, that the latter would have any effects on the former. And yet, while subsequently withdrawn, the folks at the Cochrane reviews felt it was a reasonable to perform a meta-analysis on nonsense.
Cochrane Reviews and the flu vaccine
Fortunately no one needs to go one on one with Death with oscilliococinum as your wingman. It has been a very quiet flu season. Much better than last year, when, thanks to H1N1 we were maxed out in the ICU.
There is a better way to prevent the flu than dilute, liquified duck innards. The flu vaccine. The Cochrane folks put out an update of their systematic review for the effectiveness of influenza. And their conclusions? It is not the greatest vaccine but effective.
In the relatively uncommon circumstance of vaccine matching the viral circulating strain and high circulation, 4% of unvaccinated people versus 1% of vaccinated people developed influenza symptoms (risk difference (RD) 3%, 95% confidence interval (CI) 2% to 5%). The corresponding figures for poor vaccine matching were 2% and 1% (RD 1, 95% CI 0% to 3%). These differences were not likely to be due to chance. Vaccination had a modest effect on time off work and had no effect on hospital admissions or complication rates. Inactivated vaccines caused local harms and an estimated 1.6 additional cases of Guillain-Barré Syndrome per million vaccinations. The harms evidence base is limited.
AUTHORS’ CONCLUSIONS: Influenza vaccines have a modest effect in reducing influenza symptoms and working days lost.
You get the feeling it pains them to admit the flu vaccine has efficacy, what with the caveat “In the relatively uncommon circumstance of vaccine matching the viral circulating strain and high circulation” in the conclusion.
And then, the weirdness in the abstract:
WARNING: This review includes 15 out of 36 trials funded by industry (four had no funding declaration). An earlier systematic review of 274 influenza vaccine studies published up to 2007 found industry funded studies were published in more prestigious journals and cited more than other studies independently from methodological quality and size. Studies funded from public sources were significantly less likely to report conclusions favorable to the vaccines. The review showed that reliable evidence on influenza vaccines is thin but there is evidence of widespread manipulation of conclusions and spurious notoriety of the studies. The content and conclusions of this review should be interpreted in light of this finding.
Fine. Who pays for the study can subtly bias the outcomes. I have written about that before. It does not necessarily discredit a study, but you do have to read and interpret the studies carefully and take the conclusions with a bit of salt substitute.
That is where, I thought, a meta-analysis comes in. Someone like Cochrane reviews the data with no concern about the quality of the journal or notoriety of the references. The Ccochrane reviews, I thought, looked at the numbers unbiased by the spin in the conclusions or where it was published.
So I can only think of two reasons why this warning was published.
1) The authors do not like the conclusions from the data, and are undermining the result, spinning the abstract to try and sway the message casual readers will take away from the review.
2) The authors are saying they are biased by the conclusions in the papers and the notoriety of some studies and as a result their analysis of the numbers is not to be trusted. In other words, they are incredulous rubes who just fell off the turnip truck and were sold a bill of goods by those city slickers with their manipulated conclusions and spurious notoriety. Sad either way.
The discussion is odd, with the authors saying that everyone misuses their meta-analysis and ignores the data.
Both generalizations are not supported by any evidence and seem to originate from the desire to use our review to support decisions already taken. The misquotes appear to be based on both the abstract and Plain language summary (which is what you would expect from a superficial reading of the review by people with a specific agenda).
They also use significant column inches to demonstrate just how the ACIP misquoted them.
The CDC authors clearly do not weight interpretation by quality of the evidence, but quote anything that supports their theory.
What a weird, petulant little potshot at the CDC. I could see a statement like that maybe in an editorial, definitely in a blog entry, but in the text of a major review? It makes me wonder if the Cochrane reviews have any editorial oversight for their content. If they do, then their editors have some splainin’ to do as to how a major evidence based review could revert to ‘Mommy, mommy, I don’t like the way the CDC is playing with my ball and they are calling me names. Make them stoooopppp.’
It is like reading a review of gold mining efficacy and the purity of the mined gold, and the author noting that some of the mines are near Las Vegas, a den of sin and that gold miners discuss mining at the roulette tables and sometimes the gold in made into baubles that decorate painted women, so the content and conclusions of the mining review should be interpreted in light of these findings. So weird.
It is probably projection on my part, but I find the Cochran reviews on influenza vaccination to be biased against the flu vaccine in a subtle way that I do not see in the other reviews. The oscillococcinum review, while fundamentally stupid given the nature of the intervention, brainlessly followed the data, even though there was no plausibility for the intervention.
The choice of adjectives used by the authors seem designed to cast doubt on vaccine efficacy. Now I am a vaccine proponent, and I could very well be reading into the text something that is not there. For an example, the plain language summary says
Inactivated influenza vaccines decrease the risk of symptoms of influenza and time off work, but their effects are minimal, especially if the vaccines and the circulating viruses are mismatched.
Minimal: of a minimum amount, quantity, or degree;
The data says
In the relatively uncommon circumstance of vaccine matching the viral circulating strain and high circulation, 4% of unvaccinated people versus 1% of vaccinated people developed influenza symptoms.
In a country the size of the US, that is the difference between 12 million and 3 million getting flu if everyone were vaccinated (yes, I know, all 300,000,000 Americans are not healthy adults). Worst case, it would be 6 million vrs 3 million. Still, across the whole population of the country, that would not be a minimal effect.
Or the number needed to treat:
The combined results of these trials showed that under ideal conditions (vaccine completely matching circulating viral configuration) 33 healthy adults need to be vaccinated to avoid one set of influenza symptoms.
In comparison, there are 250,000 new cases of Hepatitis B each year in the US and maybe 4000 HPV related cancer deaths a year in the US. Are the effects of the flu vaccine minimal in preventing these diseases? Maybe. But that is a judgement call, not a medical call.
Flu vaccine seems good intervention, a reasonable bang for the buck. I would say it is a moderately effective vaccine with widespread health benefits beyond the prevention of acute influenza (see below). The cost effectiveness of flu vaccination is debatable and is ultimately a value judgment. In medicine they try an calculate the quality-adjusted life-year of an intervention to see if it is worth it to society.
It is form of evaluation that makes my brain hurt and I lack the knowledge to do much except to take them at face value. The outcome of cost-effectiveness evaluations depends on the assumptions made. For the elderly, you get conclusions like this:
Vaccination was cost saving, i.e., it both reduced medical expenses and improved health, for all age groups and geographic areas analyzed in the base case. For people aged 65 years and older, vaccination saved $8.27 and gained 1.21 quality-adjusted days of life per person vaccinated. Vaccination of the 23 million elderly people unvaccinated in 1993 would have gained about 78 000 years of healthy life and saved $194 million. In univariate sensitivity analysis, the results remained cost saving except for doubling vaccination costs, including future medical costs of survivors, and lowering vaccination effectiveness. With assumptions most unfavorable to vaccination, cost per quality-adjusted life-year ranged from $35,822 for ages 65 to 74 years to $598,487 for ages 85 years and older.
In the US a cost per quality-adjusted life-year of around $50000 is considered acceptable for an intervention.
It appears to me that the authors of the Cochrane reviewers think flu vaccination is not a worthwhile public health intervention, which is fine, but quit being a weasel and hiding behind words like minimal and complaining that people misuse your reviews for their own ends. The get close to admitting this in the discussion:
Given the limited availability of resources for mass immunization, the use of influenza vaccines should be primarily directed where there is clear evidence of benefit.
If I waited for clear evidence in medicine I would treat no one. However, the preponderance of data from basic principals to epidemiology to clinical trials leads me to conclude that the flu vaccine is moderately effective and cost effective. Someday, I hope, they will develop the universal flu vaccine and then, with universal vaccination, we will get rid of flu morbidity and mortality. But, to quote Rumsfeldt, I have to fight the wars with the weapons I have.
The Cochrane reviewers appear to be whiny, little babies. BTW. It is not an ad hominem since I do not think the review is wrong or flawed because they are crybabies. The substance is fine, the style is whiny crybaby. Boo frigity who. Got an issue? Here’s a tissue.
Either way, the confidence I have in the Cochrane reviews, at least as far as influenza vaccine goes, is now at an all time low.
A cherry picked study
There are multiple potential benefits from the flu vaccine:
1) You do not get the flu this year.
1a) You have a milder case of flu.
b) You do not pass the flu to others.
iii) You do not die of flu.
IV) You do not die of short term complications of flu.
FIve) You do not die of long term complications of flu.
6) You may not get the flu in the future with other strains. It would appear that those who had the 1976 swine flu vaccine has some protection against the 2009 strain and since strains of flu keep returning, if there is a mismatch in the flu and the vaccine this year, it may give you benefit in the future.
One of the arguments against the efficacy of the flu vaccine as a preventative against death is the fact that those who get the vaccine have decreased mortality when there is no circulating flu. It is suggested that the decreased mortality is not due to the flu vaccine, but that those who get the vaccine are healthier.
Could there be an alternative explanation?
There are two ongoing themes in the ID literature that have yet to overlap. One is people who get severe infections that require hospitalization not only have increased short term mortality, but long term mortality as well. Why they die is not as well worked out, but in those who die after pneumonia have increased inflammatory markers at discharge.
The other theme is that inflammation is a prothombotic state and patients with acute infections are more likely to have strokes, heart attacks and pulmonary embolisms and that risk of vascular events can be elevated for up to a year. Even an aggressive tooth cleaning increases the risk for a vascular event.
The rate of vascular events significantly increased in the first 4 weeks after invasive dental treatment (incidence ratio, 1.50 [95% CI, 1.09 to 2.06]) and gradually returned to the baseline rate within 6 months.
I have said before that if probiotics could really boost your immune function, they should also increase vascular events like stroke and heart attack.
Infection leads to inflammation leads to clot leads to vascular events. If you could stop that cascade, say with a vaccine, you could conceivably decrease the number of deaths. And so it does with a combination of the flu and pneumococcal vaccine.
Of the 36,636 subjects recruited, 7292 received both PPV and TIV, 2076 received TIV vaccine alone, 1875 received PPV alone, and 25,393 were unvaccinated, with a duration of follow‐up of 45,834 person‐years. Baseline characteristics were well matched between the groups, except that there were fewer male patients in the PPV and TIV group and fewer cases of comorbid chronic obstructive pulmonary disease among unvaccinated persons. At week 64 from commencement of the study, dual‐vaccinees experienced fewer deaths (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.55–0.77]; P<.001) and fewer cases of pneumonia (HR, 0.57; 95% CI, 0.51–0.64; P<.001), ischemic stroke (HR, 0.67; 95% CI, 0.54–0.83; P<.001), and acute myocardial infarction (HR, 0.52; 95% CI, 0.38–0.71; P<.001), compared with unvaccinated subjects. Dual vaccination resulted in fewer coronary (HR, 0.59; 95% CI, 0.44–0.79; P<.001) and intensive care admissions (HR, 0.45; 95% CI, 0.22–0.94; P=.03), compared with among unvaccinated subjects.
Note: the beneficial effects occurred up to 64 weeks after receiving the vaccines; influenza vaccine could conceivably protect from death outside of flu season because vaccination prevents the sustained detrimental inflammatory effect of infections.
This result does not hold true in every study, but the data suggests that the beneficial effects of preventing influenza are wide-ranging and not limited to avoiding an acute viral pneumonia. The effects of both influenza and the vaccine are more complicated than a simple flu vaccination prevents flu.
There are two statements that pretty much ensure that the writer is an influenza goof.
One is that the H1N1 pandemic last year was no big deal. I do not know what planet they were on, but H1N1 brought my hospitals right to the edge of the volume of severe illness we could handle. In my system we also had around 10 deaths, several in pregnant females and all in young people. In 25 years I had never had a young person die of acute influenza until last year, and I do not want to repeat the experience.
One of our hospitals is a Trauma Center and we able to save a few patients who would have otherwise died because we offer ECMO. While the epidemic was not particularly virulent compared to historical disasters like the 1919 pandemic, it was the worst flu season I have experienced.
The other statement is that the CDC is “backing off” the claim that influenza kills 36,000 people a year, as if the prior estimates were a lie.
The problem with medicine is we develop better methodologies and techniques to try to answer difficult questions. How many people die of influenza? For years the answer has been around 36,000 and I have discussed the paper that resulted in that number. It was, like all epidemiologic studies, imperfect, but was the best at the time. Now they have a better study.
For H1N1 in 2010, the estimates for total direct and indirect deaths is ~12,470, with a range from ~8,870 to ~18,300. Certainly less than 36,000. How about other years? Turns out that, like much of medicine, the answer is complicated and depends on the year and the circulating strain of flu. Some years are better than others. Estimated number of annual influenza-associated deaths with underlying pneumonia and influenza by age group — United States, 1976–77 through 2006–07 influenza seasons cause was 6,309 deaths a year, with a minimum of 961 and a maximum of almost 15,000 deaths, plus or minus the usual margin of error.
The estimated number of annual influenza-associated deaths with underlying respiratory and circulatory causes, by age group — United States, 1976–77 through 2006–07 influenza seasons was an average of 23,000 deaths with a minimum of 3000 and a maximum of 48,000.
Like so much in medicine the answer hinges on the phase ‘it depends.’ The CDC used more sophisticated techniques and came up more nuanced numbers. When someone asserts that the CDC is backing away from prior numbers, you know they have no understanding of medicine or epidemiology and the constant urge to improve. Unlike most SCAM’s, which have made almost no substantive improvements since their founding. Of course you cannot improve on perfection. Or increase by multiplying something by zero.
So get the vaccine and avoid the o-so-silly-o-coccinum.