Look!  A metaphor!

Look! A metaphor!

I don’t know the best metaphor. What comes around goes around. The more things change, the more they say the same. Sisyphus. Whack-A-Mole.

So what to do when the same old same old rears its head yet again? There are 2,545 posts on this blog, and I suppose I could just point to prior posts. But a blog entry that consists of links to prior posts would make the managing editor irritable. And we don’t want him irritable. Although those links are at the end of the post.

And WordPress is not a good format for reference material. I have trouble finding my own articles even when I know they exist and search for them using what I think are relevant terms.

It being the start of the flu season the same ole same ole nonsense is back about flu vaccines and influenza treatment. Influenza seasons vary, the nonsense does not. On the assumption that most of the readers of the post have no prior knowledge of what I have written on the topic, I thought I would tackle influenza yet again.

The other problem with writing is the lack of the context we rely upon with spoken language. No tone, no facial expressions, no body language. Just words, and words do not always convey some forms of subtlety.

Sarcasm at least has punctuation although I have never seen it used. There is also a sarcastic font, a reverse italic. And I suppose you could always sure fake markup, <sarcasm>enclosing the comment in tags</sarcasm>. All the solutions are a poor substitute to a sneering tone and a curled lip. When you have to tell someone that a comment was sarcastic, or a joke, the sarcasm loses most of its power.

I don’t need sarcasm today. I need an eye roll. I know there is now an eye roll emoji available, but not on this version of Word Press, and the emoji would have the same killing effect of the sarcmark.

Look how expressive all these eye roll gifs are. For this entry, think of the Liz Lemon eye roll with every quote. Because the eye roll is there in my heart as I write this post, induced by:

Questioning Medicine: Why Is Tamiflu Still Around? Tamiflu doesn’t help, so why are docs still prescribing it?

Over at MedPage today. By a Family Practice Resident. Sorry Harriet, but I am channeling my internal medicine/ID specialist arrogance and I can now see out of the back of my head. I think I just tore both my superior obliques. I work in a hospital system with internal medicine residents. And they are Jon Snow when it comes to infectious disease. Which is expected. They do a residency to learn. But I would be surprised if anyone would want to demonstrate the depth of their Snow* with a blog entry on a major medical website. Not here. And I thought naturopaths had issues with understanding their limitations.

The article is a year old, but representative of the same old crap and the internet is eternal. I appreciate that it is fun to be edgy and contrarian, going against the conventional wisdom. I really do. But if you are going to be an edgy contrarian, do so after reading all the literature.

They start by mentioning the issues with Roche failing to report all the data from all the clinical trials and the brave crusade of Dr. Jefferson to get all the data.

Yep. Roche has behaved like dirtbags when it came to releasing information on the efficacy of oseltamivir. But, as has been discussed, the Cochrane reviewers are not angels either. Knowing the biases of the Cochrane reviewers and their awesome ability to evidently pull out of thin air explanations for the mechanism of oseltamivir’s effects, I do not trust their meta-analysis. They fall in the category of:

…a controversial tool, because even small violations of certain rules can lead to misleading conclusions. In fact, several decisions made when designing and performing a meta-analysis require personal judgment and expertise, thus creating personal biases or expectations that may influence the result.

Bibo: bias in, bias out. Cochrane stinks of bibo. Like this entry, n’est-ce pas?

And then the edgy contrarians proceed to cherry pick the results of the bibo Cochrane review that suit their narrative that oseltamivir is a useless drug. They say:

When the Cochrane reviewers were finally able to look at and sort through the body of information, and not just the abstract data, they came to similar conclusions, and reported that there were no differences for hospital admissions, reductions in confirmed pneumonia, or other complications.

What they do not mention from the bibo Cochrane review? What do they leave out of their edgy contrarian essay?

Oseltamivir and zanamivir have small, non-specific effects on reducing the time to alleviation of influenza symptoms in adults, but not in asthmatic children. Using either drug as prophylaxis reduces the risk of developing symptomatic influenza. Treatment trials with oseltamivir or zanamivir do not settle the question of whether the complications of influenza (such as pneumonia) are reduced, because of a lack of diagnostic definitions

What are the small, non-specific effects?

For the treatment of adults, oseltamivir reduced the time to first alleviation of symptoms by 16.8 hours (95% confidence interval (CI) 8.4 to 25.1 hours, P < 0.0001). This represents a reduction in the time to first alleviation of symptoms from 7 to 6.3 days.

So you are sick for about day less with oseltamivir. It figures that privileged physicians, with money and resources, would poo-poo a mere day of less illness. They are not single parents working minimum wage for whom getting back to work a day sooner may be critical to making the rent payment or putting food on the table. There are large numbers of people for whom an extra-day of illness could be catastrophic, not that a FAMILY PRACTICE resident would be aware of that. I certainly take care of those patients on a daily basis. Unfortunately, these are also the same patients who would be unable to afford oseltamivir.

And being able to prevent influenza in family members or in nursing homes is not a small, non-specific effect either.

The majority of these clinical trials are mostly in normal people. Could oseltamivir have other benefits than those mentioned by the very bibo Cochrane review? Again, it depends on what population you are treating and how promptly medication is given.

My favorite endpoint is death. A nice, binary endpoint with no issues about diagnostic definition. Death is easy to diagnose, just look for the sobbing family at the bedside as their 25 year old daughter goes into influenza-induced multi-organ system failure, the EKG slowing to flat line. Been there. Done that. Too many times. Not a fan.

What about oseltamivir and death? In Asia, prompt use of oseltamivir meant:

The incidences of hospitalization and the mortality were lower

If pregnant:

As compared with early antiviral treatment (administered < or = 2 days after symptom onset) in pregnant women, later treatment was associated with admission to an intensive care unit (ICU) or death (relative risk, 4.3).

If elderly:

oseltamivir therapy initiated after 48 hours (OR = 3.32, 95% CI = 1.02–10.8, P = .04) were identified as independent variables associated with mortality

If in Thailand:

Treatment with Oseltamivir is associated with survival in hospitalized human influenza pneumonia patients.

In AIDS patients:

Delayed administration of oseltamivir in hospitalized patients was significantly associated with mortality (P = 0.0022).

That is a fairly consistent finding. In at-risk populations (humans), prompt use of oseltamivir decreases the risk of death. And at $135 dollars, it is a lot less expensive than the $10,000 average cost of a funeral.

And if you are ill enough to be admitted to the hospital with influenza, early oseltamivir leads to less progression.

And at what cost? Nausea, vomiting, and headache. Those who let the bibo Cochrane reviews do their critical thinking for them are impressed with the number need to harm of 28 for nausea, 22 for vomiting, and 32 headaches. As if you can’t stop the medication or treat the symptoms if the potential benefit, depending on the patient population, is death. Let’s see. Death. Nausea. Death. Vomiting. Death. Headache. I’d tend towards avoiding my death and I would hope my doctor would as well.

Death sucks.

I remember 2009, the first year for H1N1. Every ICU bed in our system was occupied and every ventilator was in use. If a patient came in with flu needing a ventilator we had nothing to offer. They were dead. We were maxed out. It still amazed me that influenza peaked right at our surge capacity. It was also a year with 12 flu deaths in my system, mostly in the young and the pregnant. More flu deaths than I had ever seen before. Did putting all our flu patients on oseltamivir prevent a few deaths? Probably. I can’t say based on my own experience.

As an ID doc I am aware of the 1919 influenza pandemic. Flu killed maybe 5% of the world in 6 months. 650,000 deaths in the US, about to equal to all combat deaths in all of our wars. Influenza can be quite the killer and should flu ever return with a repeat of 1919, I’ll be glad to have some oseltamivir around to take the edge off the death rates. Oseltamivir isn’t anywhere as effective as penicillin for lues, but it is better than nothing.

There are 85,373 Pubmed references for influenza and 3,315 for oseltamivir. It looks like the authors read about a dozen papers. I wonder how many I have read in my 30 years of ID? Since starting the Puscast in 2006 I have reviewed about 3,200 articles related to influenza. At least that is how many pdfs I have on my hard drive tagged as influenza.

The influenza literature is, like most of medicine, complex, nuanced, and difficult, and it has to be applied thoughtfully to a patient population that it equally complex, nuanced, and difficult. Understanding influenza is more than writing a prescription for a patient. Understanding influenza is more than taking at face value a bibo Cochrane review. It is being a truly holistic doctor, factoring in the circulating strains of flu, the prior exposure/vaccination history, the co-morbidities of the patient and their close contacts and family, and their possible genetic resistance or susceptibility to influenza. Influenza is a disease of individuals, families, and populations.

So when I read a glib, superficial conclusion like:

Patients who have the flu feel bad, they want a drug to help them feel any amount of relief. Sadly, we have nothing for them. We can encourage hydration and rest, but that’s about it.

The easy path is to write a prescription for Tamiflu and move to the next patient. The hard path is to discuss why you are not going to write the script to someone who doesn’t want to hear it.

As with most things in medicine, we should do our best till we know better, and when we know better we should do better.

It’s safe to say with Tamiflu, as well as with the medical topics in previous posts, we know better!

I can’t even roll my eyes. JFC. I can only shake my head in sad disbelief and pity his future patients with influenza. I cannot find a GIF that is equal parts contempt and disgust. Because this is the kind of simplistic meme that will circulate among those who don’t recognize the how profoundly misleading it is.

In my practice I see the most patient harm occurs from those who honestly think they know what they are doing about infectious diseases but in fact do not know the difference between a burro and a burrow. Ignorance kills. It will be my colleagues, the ICU docs and nurses and RT’s, who deal with the results, at the bedside as the patient fades to black from influenza.

The good news? Now, when I discuss Dunning-Kruger I have an even better example than Jenny McCarthy.

More than you want to know about influenza

* I am particularly proud of that sentence. Just saying.



Posted by Mark Crislip

Mark Crislip, MD has been a practicing Infectious Disease specialist in Portland, Oregon, since 1990. He is a founder and  the President of the Society for Science-Based Medicine where he blogs under the name sbmsdictator. He has been voted a US News and World Report best US doctor, best ID doctor in Portland Magazine multiple times, has multiple teaching awards and, most importantly,  the ‘Attending Most Likely To Tell It Like It Is’ by the medical residents at his hospital. His growing multi-media empire can be found at edgydoc.com.