An ongoing dialogue on HIV/AIDS, infectious diseases,
October 24th, 2015
Pumpkin-Flavored ID Link-o-Rama
As the leaves change colors and fall from the trees, the days grow shorter and colder, and pumpkin-colored and flavored merchandise shows up everywhere, I ask you this important question:
What precisely are the infectious risks of bobbing for apples?
Off we go.
- Receiving antibiotics in childhood is associated with weight gain. The important finding in this study is that the effect occurs throughout childhood, not just infancy. Could it be that the antibiotic-obesity association will have a greater effect in reducing outpatient use of antibiotics than the risk of resistance? Lots of press coverage.
- At the other end of the age spectrum, here’s a thoughtful perspective on the widespread use of antibiotics at the end of life. I’ve covered this topic before — why are antibiotics so often given at the end of life when all other medical interventions are stopped? Paper cites one study suggesting “greater comfort, albeit shorter survival, among patients with advanced dementia and suspected pneumonia who were not treated with antimicrobials.” Sounds like withholding antibiotics could be the right move in palliative care.
- HCV therapy with paritaprevir/ombitasvir/ritonavir may precipitate hepatic decompensation and liver failure. Not surprisingly, “most” of the cases (which have precipitated an FDA-mandated label change) have occurred in patients with advanced cirrhosis.
- There are infectious risks associated with receiving injections of live cells, including Q fever from sheep cells and M abscessus from human fetal cells. Certainly infection is one good reason not to undergo these treatments; the second and even better one is that none of these therapies has any proven medical benefit. A bit more on this longstanding form of quadkery here.
- The ocular syphilis cluster on the West Coast is a reminder that in the post-PrEP, post treatment-as-prevention world, condomless sex is inevitably increasing among MSM, along with rates of sexually transmitted infections. Note that this report repeats the recommendation that all patients with ocular syphilis should 1) undergo a CSF exam (which may be negative in ocular syphilis) and 2) be treated for neurosyphilis regardless of CSF results. Which prompts me to ask — then why do the CSF exam if treatment isn’t changed based on the results?
- Transmitted NNRTI resistance does not appear to influence response to integrase-based ART. This nice analysis presented at IDWeek from a Stanford/Kaiser collaboration confirms previous reassuring findings from prospective clinical trials. And it means you probably don’t need to use a boosted PI in this situation.
- Promising results from a small (n=20) single-arm pilot study of two-drug, dolutegravir + lamivudine ART in treatment-naive patients. Think GARDEL strategy, only with DTG and not LPV/r. 20/20 are virologically suppressed at week 24, and all but one were < 50 by week 8. Note that the inclusion criteria limited enrollment to patients with HIV RNA < 100,000 and CD4 > 200. A larger (but still not comparative) clinical trial of this strategy is opening soon.
- In the vaccine world, is there anything more complicated than the recommendations for meningococcal immunization? Based on a meeting that took place this June, they’ve now changed again to include the serogroup B vaccine for late adolescents. When in doubt on vaccine-related issues, head over to the invaluable immunize.org site, in particular the “Ask the Experts” section.
- No clinically significant drug-drug interactions between ECF-TAF or RF-TAF and sofosbuvir/ledipasvir. Even with the ledipasvir slightly boosting tenofovir exposure, levels remain 5X lower than when TDF is used. ECF-TAF (“Stribild 2.0”) approval expected next month, RF-TAF (“Complera 2.0”) next year.
- Here’s a nifty case report: A 91-year-old man had 10 separate hospital visits for fevers, chills, and hypotension over a two year period, several times with positive blood cultures for Aeromonas hydrophila. The source? Contaminated well water. My favorite quote from the paper: “Culture results revealed significant overgrowth of A hydrophila from his master bathroom sink; he used this water supply to soak his dentures nightly.” Made me think of this household product — he’s old enough to have watched that ad.
- On the topic of great cases, here’s a very nice inaugural piece on the In Practice blog by Harrison Reed, who reminds us that these rare and astounding cases — zebras — are vastly outnumbered by the more common cause of hoofbeats, horses.
Warning, adult content time. In her HBO special, Amy Schumer not surprisingly has a plenty of ID-related jokes — including this surprising one:
I was dating an Infectious Diseases doctor, cause two birds …
How convenient! And by the way, Amy — if you need a new writer, you know where to find me! Right here — and now on Twitter at @PaulSaxMD.
[youtube http://www.youtube.com/watch?v=5HlImrCEkWo&w=560&h=315]
October 17th, 2015
Dear Flu Vaccine: Please Improve!
Dear Flu Vaccine,
As the supply of you and your brethren have arrived in our clinics, on our hospital floors, and in pharmacies, I thought it would be a good time to reach out and tell you how to get better.
That’s right — here, free of charge, is a to-do list for how you can improve.
Understand, I’m one of your top “boosters” (sorry for the pun), and of course I got mine this year — as I do every year. You’re better than nothing, after all.
But as a patient of mine refused his flu shot this past week — “it gives me the flu” he (wrongly) said — I became motivated to reach out and let you know exactly what you should start working on:
- Become more effective. I’m sure you think that the less said about last year’s effectiveness the better, but really — 19% protection? That’s pretty lame, my friend! Your usual 60% protection seems kind of awesome by comparison, doesn’t it, and even that’s no great shakes. OK, ok, I realize it’s because the vaccine strains didn’t precisely match the circulating ones last year, but c’mon. You can do better than that. I know you can.
- How about some durability? Let me list the number of vaccines we recommend to our patients every year.
1) Flu.
That’s it — you’re the only one. And you don’t want to be in this exclusive club. It’s no wonder that many people act like it’s tax day when you tell them that the flu vaccine is due. Again? Didn’t we do just do this, like, yesterday? - Give us fewer options. Must you come in so many different forms? It’s too complicated, like trying to choose a breakfast cereal in a big supermarket. Don’t you know that too much choice is paralyzing? Trivalent. Quadravalent. High dose. Regular dose. Attenuated intranasal mist. Recombinant egg-free. Free range and gluten- free. (I made that up.) Please, enough already. Even the vaccine experts at ACIP can’t (or won’t) make a firm recommendation. This is what they say: “For persons for whom more than one type of vaccine is appropriate and available, ACIP does not express a preference for use of any particular product over another.” Thanks, really helpful. Now what?
- Be more reliably available. Supply is notoriously erratic. Sometimes the hospitals get flu vaccines first; sometimes the pharmacies; sometimes the community-based practices. Sometimes there are no vaccines for babies. There are shortages some years — then it’s like a new iPhone release, generating absurd lines — and too much supply the next, you can’t give the things away. This year it’s the nose spray vaccine — where is it? Next year it will be — who knows? Figure it out already!
- Develop an easy, universal tracking system. People can get flu shots in so many different locations we have no idea whether our patients have received them. Doctors’ offices. Pharmacies. On the job. Pop-up “flu clinics” at the neighborhood mall, church-temple-mosque, community center. Toll booths and fast food drive-thrus (throughs?) will be next. While we like the widespread availability, it makes quality assurance programs all but impossible. Here’s an idea — how about a web site, igotmyflushot.org, where people can enter their name and date of birth, and electronically release the information to their doctors? Yes, I know it’s a great idea. You’re welcome.
- Make it more understandable what you prevent. Email from non-MD friend:
Friend: “Is there flu about? Wife has fever, nausea. Son too.”
Me: “Yes there’s flu. But flu is mostly a respiratory illness — cough, sore throat, that kind of thing. Sounds like they have a stomach bug.”
Friend: “Oh yeah. Both had questionable chicken tacos at State Fair yesterday.”
Ok, maybe this misunderstanding isn’t really your fault. But somehow I believe that if you were more effective, the public would have a clearer understanding of what you prevent (on a good year) and what you don’t, and more confidence that they received something that works. Here’s what you prevent: Influenza. Here’s what you don’t prevent: Colds. Stomach bugs. Various other causes of fever. Is that so hard?
Remember, I offer the above suggestions even though I’m a strong advocate of getting the flu vaccine. It does work sometimes, influenza is a miserable illness, and frankly one could justify it solely on altruism — who wants to be the disease vector that triggered a hospitalization in a baby, a frail elderly person, or someone with a weakened immune system?
Still, there’s room for improvement. Ok, lots of room. And we can dream, can’t we? Just like the guy in the video below.
Signed,
An Infectious Diseases Doctor with a Slightly Sore Left Arm (but it’s not too bad)
[youtube http://www.youtube.com/watch?v=gasAm4DIVsg&w=560&h=315]
October 13th, 2015
Yes, There Are Important HIV Studies at ICAAC and IDWeek — Here’s One
Both ICAAC and IDWeek (formerly IDSA) are now over, IDWeek ending this past Sunday.
These are the two large Infectious Diseases scientific meetings that take place each year in the Fall. They’ve been battling it out for years for attendance, but it looks like finally IDWeek (formerly IDSA) has won the Fall slot — ICAAC is moving next year to the Spring, where I assume it will stay.
Regardless of which meeting one attends, or when they happen, a common complaint heard from HIV-specialist types goes like this:
Well, it’s not like CROI — hardly anything here new and important.
Well, of course it’s not like CROI — that’s a whole meeting devoted to HIV research, both clinical and basic. It’s unreasonable to expect there will be anywhere near the number of oral sessions, posters, and plenaries on HIV at non-CROI meetings because, obviously, ICAAC and IDWeek have to represent the full breadth of material in the field.
But there usually is some good stuff, studies that could significantly impact clinical practice. Here’s the most important HIV study from ICAAC, and soon the notable ones from IDWeek.
In the STRIIVING study, 551 virologically suppressed patients were randomized to stay on their regimen or to switch to ABC/3TC/DTG; it was open label (images thanks to the essential natap.org):
Eligibility criteria included being on first or second regimens with no history of treatment failure, and HLA-B*5701 negative.
At the end of 24 weeks, treatment success (HIV RNA < 50 copies by “snapshot”, meaning also still in study) was observed in 85% and 88% of subjects in the switch vs continue current ART arms respectively:
There were no virologic failures or emergent resistance in either arm. 4% (10 total — not 10% as I erroneously wrote) of the ABC/3TC/DTG group stopped the study due to adverse events (none considered serious) vs. zero in the continued ART arm. Treatment satisfaction at week 24 was significantly higher for those on ABC/3TC/DTG.
A few comments on these results, which were both reassuring and disappointing at the same time:
- There are now four available single-tablet treatments for HIV, and all have had prospective, randomized switch studies similar in many ways to this one — previously TDF/FTC/EFV, TDF/FTC/RPV, TDF/FTC/EVG/COBI for PI and NNRTI switches.
- Up until now, all of these studies numerically (if not significantly) favored the switch to the single tablet — not really surprising, as patients entering these studies typically want to simplify their regimens.
- Why didn’t this happen in STRIIVING? I can think of three kind of overlapping reasons: 1) A high proportion of subjects were already receiving integrase-based (and hence well-tolerated) treatments; 2) Also a high proportion were already on single-tablets; 3) All of these single-tablet treatments (before this one) would necessarily include TDF/FTC, and many of the multi-tablet regimens would as well. There’s probably a somewhat less-favorable tolerability profile of ABC compared with TDF, independent of hypersensitivity reactions (which didn’t happen in this study, obviously, since all were HLA-B*5701 negative).
An interesting irony is that the SINGLE study — which emphatically put DTG on the map — demonstrated superiority of ABC/3TC + DTG over TDF/FTC/EFV, results driven by better tolerability. Think about that one, and what it says about efavirenz.
Take-home message? Switching to ABC/3TC/DTG will mostly be successful (especially virologically), but a small fraction might have side effects that makes them prefer what they’ve already been on.
Anyway, that’s the most important HIV study at ICAAC. Coming soon, the most important one (or two or three, haven’t decided yet) at IDWeek.
Good time for a baseball moment. Congrats, Cub fans! (So far.)
[youtube http://www.youtube.com/watch?v=WOYME2Q4nAg&w=560&h=315]
October 7th, 2015
The Future of Diagnostic Microbiology, in 17 Minutes!
Over at Open Forum Infectious Diseases, I had the pleasure to interview Dr. Angela Caliendo about the latest advances in diagnostic microbiology. She touches on molecular testing in general, rapid pathogen identification (especially with MALDI-TOF, everyone’s favorite acronym), “syndromic” diagnostic testing for respiratory infections and diarrhea, use of Xpert for TB even here in the United States, and, of course the cost of implementing all these new technologies.
It’s incredibly entertaining, especially for ID geeks like me, and that’s because of the person I’m interviewing. Here are few key facts about Dr. Caliendo:
- She goes by Angie.
- She’s Professor of Medicine at Brown, and Vice Chair of the Department of Medicine. Before that, she was the Medical Director of the microbiology lab at Emory for 14 years.
- She’s one of those rare individuals who understands both the clinical and the laboratory side of medicine, an MD/PhD who really does blend both of those degrees.
- She’s an incredible teacher. If you’re looking for a Grand Rounds speaker on an ID topic, look no further!
- She’s been a major driver in the effort to improve diagnostics in Infectious Diseases, and was the lead author in this widely cited position paper.
Angie and I were medical residents and ID fellows together (a few years ago, ahem), and I can only remember one weakness (if you can call it that) — she has a horrible sense of direction. Really hopeless. I once told her to drive “towards the river” two blocks away from the Charles, and she looked at me as if I’d asked her to navigate to Mars. She admitted that she only knew where the river was if she could literally see it.
Aside from that, however, working with Angie was all gold.
Interview here, transcript here.
October 1st, 2015
WHO Decision to Recommend Treatment for All with HIV an Easy One — Now Comes the Hard Part
In the newspaper today — and yes, we still do get it delivered (some habits die hard) — is this headline:
Millions More Need H.I.V. Treatment, W.H.O. Says
It’s true — these updated guidelines say that all should be treated soon after diagnosis, regardless of CD4 cell count or whether they have symptoms.
Now, a certain non-ID doctor read the headline this morning, and asked me what the big deal is. After all, she’s been hearing about our treating everyone with HIV here for years — since 2012, if you want to be precise about it.
Even before that, in trendy San Francisco, the Department of Public Health in 2010 recommended treatment for all people with HIV regardless of CD4 cell count. Today this decision is paying big dividends in that city, with a decline in new HIV diagnoses probably linked to this policy in action.
Indeed, given the results of the START, TEMPRANO, and HPTN 052 studies, the WHO’s decision to modify its recommendation is about as surprising as Jerry’s telling George, Kramer, and Elaine that he wants to have lunch at Monk’s.
(Not sure why I thought of that analogy. Must be hungry.)
The data are now so overwhelmingly in favor of universal treatment of HIV infection that I can only think of one subset of patients for whom therapy has not been proven to be beneficial. These are the rare “HIV controllers” with undetectable virus and normal CD4 cell counts even without treatment. My hunch is that it probably benefits them too, though this is still under study.
The challenge, of course, is putting the “treat-all” policy into action. In Sub-Saharan Africa, the UNAIDS estimate of the proportion of people living with HIV who have been diagnosed is only 51%. Obviously, the other 49% are not getting any sort of treatment unless there is a massive HIV testing campaign.
In addition, treatment of everyone will likely strain both human resources and medication supply, with an additional 9 million people eligible for treatment but no new funding source to pay for it. As such, there’s an important statement in the guidelines about whom to treat if resources are limited:
Regardless of the epidemic profile and disease burden, priority should be given to people with symptomatic HIV disease or with CD4 count at or below 350 cells/mm3 who are at high risk of mortality and most likely to benefit from ART in the short term.
In other words, if you can’t treat everyone, treat the sickest first — they have much more to gain survival-wise than healthier people with HIV, so you definitely get more for your human and pharmaceutical investment.
But are clinical programs set up to do this? I suspect that with this recent WHO Guidelines change, most will operate under a “first-come, first-served” approach, offering treatment to everyone that shows up — until medication supplies run out or the clinic gets overwhelmed. As my colleague Ben Linas noted years ago when studying AIDS Drug Assistance Program waiting lists, this is not the best approach to maximize impact with limited resources.
The change in the WHO Guidelines, unsurprising as it might be, makes good sense scientifically. Time for a different sort of science — “implementation science” — to figure out how to make it happen, and how to benefit people the most.
Back to Monk’s.
[youtube http://www.youtube.com/watch?v=8LafoDMH6Tw&w=420&h=315]
September 24th, 2015
Decision to Lower Price of Pyrimethamine a Good One, Especially Given the Weak Defense of the Price Hike
The big ID story the past couple of weeks is that the price of pyrimethamine — a drug that’s been available generically for decades — went from $13.50 to $750 for one pill after the exclusive rights to the drug were purchased by Turing Pharmaceuticals.
Now, after a barrage of criticism — all the way from this little blog to the Infectious Diseases Society of America to the New York Times to the leading Democratic candidate for President — the company has wisely decided to lower the price.
Exactly what the price will be remains to be seen, because there’s a lot of space between $13.50 and $750, but we’ll find out soon enough.
How about defense of the initial decision to raise the price?
Roll ’em:
[youtube http://www.youtube.com/watch?v=L-U1MMa0SHw&w=560&h=315]
There are a bunch of claims here that don’t quite ring quite true.
Namely:
- We don’t “desperately” need new treatments for toxoplasmosis [0’54”, those are minutes and seconds in the video]. Most people who have toxoplasmosis have asymptomatic latent infection and need no treatment. 90% of those that do develop active disease generally respond to the treatments we have. Clinically relevant resistance is, fortunately, a rare event. Alternative therapies (notably trimethoprim/sulfamethoxazole) are also pretty good, and have become standard-of-care in some settings.
- Treatment of toxoplasmosis does not cure it [5’22”] — if a patient’s immune system again becomes weakened, they can suffer a relapse even after they have been treated. This is why chronic suppressive therapy must be continued indefinitely if a patient remains immunocompromised.
- Patients with AIDS who need treatment don’t get a “very short treatment administration” [5’30”]. The HIV Opportunistic Infection Guidelines recommend 6 weeks of initial therapy, followed by chronic maintenance therapy until there is “an increase in CD4 counts to >200 cells/µL after ART that is sustained for more than 6 months.” In other words, patients treated for toxoplasmosis can easily be on treatment for a year, sometimes even longer.
The part around 2’30”, however, is undeniably true:
Profits are a great thing to maintain your corporate existence.
Look, there is nothing wrong with companies making profits for discovering, developing, and creating good products — this is a capitalist country, after all, and innovation should be rewarded. I write that sentence keenly aware that the new iPhones are about to appear in stores this weekend, and yes, my iPhone 4 is looking a little tired.
But with the pyrimethamine price increase, some sort of threshold of reasonableness was passed.
The negative response has been essentially universal, and quite appropriate.
September 20th, 2015
EHR and Drug Prescribing Warnings: The Good, the Bad, the Ugly
Part 1. The Good.
Recently, an ENT colleague (fictionally named “Clint” below), sent me two emails triggered by drug-drug interaction warnings he received while seeing HIV patients.
Here’s #1:
Hey Paul, I saw Mark C yesterday for hoarseness, and his exam was negative. Thought we’d try a PPI for reflux, but when I wrote the script, I got a warning that it interacted with Complera. Is this a real interaction?
Thanks,
Clint
And #2:
Paul, can’t believe I’m emailing you again. Same sort of question, different patient. Is there really an interaction between fluticasone nasal inhaler and ritonavir?
C
The answer, of course, is absolutely yes to both queries — these are very much “real” interactions, highly clinically significant. Rilpivirine (part of Complera) needs stomach acidity for adequate absorption. And the metabolism of fluticasone (and most other inhaled, injected, or even topical steroids) is blocked by ritonavir, raising systemic levels of the steroid and causing hypercortisolism — a very serious problem.
Good job, EHR! This is exactly what we want you to do, improve patient safety.
Part 2: The Bad.
But often the drug warnings aren’t really clinically relevant, and you just have to override (some would say “ignore”) them — which is why Clint the ENT (who, for the record, had never emailed me before) asked if these were “real” interactions.
Here’s a common example every HIV/ID provider will recognize — the patient who has been receiving TDF/FTC, atazanavir, and ritonavir for years, is doing great, and needs a refill. Up comes the following:
The first one, with “high” importance, warns of the drug-lowering effects of tenofovir on atazanavir, decreasing its effectiveness — if given “without concurrent ritonavir.” (Emphasis mine.)
Hey, EHR — can’t you tell that the patient is receiving “concurrent ritonavir”? Certainly you’d think it were smart enough to do this, as the next warning, of “medium” importance, tells you that ritonavir increases atazanavir levels — exactly what we want when we give atazanavir with tenofovir. Just check out the atazanavir package insert and all the HIV treatment guidelines.
So practically we ignore both warnings, “high” and “medium” importance notwithstanding.
With warning messages like these, I suspect the following is going on: 1) No one has taken the time to teach the EHR that the complete regimen of tenofovir/FTC, atazanavir, and ritonavir should cancel these warnings; 2) the EHR doesn’t have the internal logic to check for multi-way interactions (the program generating the top-line “high” importance warning can’t read the “medium” one); or 3) some combination of the above, lost in a tangle of computer code and overwhelmed support staff.
Bad job, EHR! If warnings become too frequent, or are clinically irrelevant, this will generate “alarm fatigue.” A clinician becomes so overwhelmed by the number of warnings that he or she inevitably starts ignoring even the important ones.
Alarm fatigue is emphatically not just a problem for ICUs with their interminable beeps and buzzes, but also for EHRs. I know several primary care doctors who say they virtually always ignore them (especially on their younger patients), and housestaff entering orders on admitted patients routinely complain these alerts slow down their work, so they learn to click right through them.
If one were feeling generous, you could argue that with this “bad” example, it’s better for the EHR to err on the side of excessive caution, especially since these drug-drug interactions do exist and are at times clinically relevant — just not in this case. This problem should eventually sort itself out with greater human oversight and EHR sophistication.
(I’m an optimist.)
Part 3: The Ugly.
Finally, sometimes the EHR alerts are just baffling. This occurred last week as I was renewing tenofovir/FTC for a patient who, for the record, has been receiving the medication for years, has normal renal function, and normal weight.
For those of you who don’t prescribe it, the recommended dose is one tablet daily of the fixed-dose combination (only one form exists).
Up came this alert:
What the …. is going on here? I’ve prescribed this medication hundreds (maybe thousands) of times, and have never seen anything like it.
On what planet is the recommended maximum dose of tenofovir/FTC 0.627 tablets a day? Or the maximum frequency 0.57 doses a day? What does 0.57 doses a day even mean?
To make sure I’m wasn’t missing something, I’ve had two smart PharmD’s review my order, and they too are perplexed.
I reported the bogus alert, so right now, somewhere in EHR support land, a group is huddling (at least I hope they’re huddling) to try and figure out what generated this bizarre warning — one, of course, that I ignored. Or more accurately, a warning I overrode by telling the EHR that the “benefit outweighs risk” when I completed the prescription.
In short, Ugly EHR! And of course with this final example, this legendary quotation comes to mind:
To Err is Human; To Really Foul Things Up Requires a Computer
Great music here, even if you’re not a fan of Westerns:
[youtube http://www.youtube.com/watch?v=WCN5JJY_wiA&w=560&h=315]
September 13th, 2015
Station Eleven Is a Very Good Read — Even for ID Doctors
One of my colleagues, an MD/PhD, stopped me after our clinical conference a few weeks ago. He does basic science research, doesn’t see patients anymore — but he still comes to our clinical conference. Definitely scores points for that. And for being a very smart, interesting, and nice fellow.
This was our conversation, reproduced verbatim:
HIM: Hey Pablo — got a book for you.
He’s called me “Pablo” ever since we went to Cuba for a scientific meeting four years ago. Yes, Cuba. Here are some pictures. And that’s one of Havana’s “taxi huevos” pictured above.
ME: Díme, Mateo.
For the record, neither one of us speaks Spanish very well. I’m pretty sure that means “Tell me, Matt”.
HIM: “Station Eleven.” It takes place in a dystopian future. Highly, highly recommended.
ME: I’m not really into science fiction. But my son is, I’ll let him know.
I’m imagining some Mad Max or Blade Runner-like thing, only a book. I can handle this post-apocalyptic theme in films (though for the record thought both of those movies were only so-so). But a whole novel? Skeptical.
HIM: It’s not really science fiction. Pretty much everyone is wiped out by the flu. It’s from the perspective of the survivors.
ME: I also don’t like books about ID topics written by non-ID doctors for non-medical readers. They get so many details wrong, it’s distracting.
Am I the only one with this view? I must have a dozen books given to me as gifts on ID topics, and most of them are terrible. One of the few I really enjoyed was My Own Country, by Abraham Verghese — and he’s an ID doctor.
HIM: No medical details, don’t worry. Weaves themes of love, art, music, journalism, religion — just what it means to be human. Really, really liked it. Tengo que leer!
I told you we don’t speak Spanish very well.
ME: OK, maybe I’ll give it a go.
Now at this point I’ll confess that the emphasis in that last sentence really should have been on the word maybe, because it just didn’t sound like the kind of book I’d enjoy.
Plus the world is filled with endless books waiting to be read, and there’s only so much time — especially with 1) Elvis Costello’s upcoming autobiography, which will be nearly 700 pages long; 2) wonderful baseball analysis like this available pretty much continuously; and 3) the imminent arrival of the next great flu pandemic, which promises to limit the free time we have available for reading quite substantially, especially if we are unlucky enough to perish in it.
But I was killing time in our neighborhood book store (how long before those are all gone, even without flu wiping us off the globe?), and the book was featured prominently in the displays. So I started reading it.
And you know what? Matt was right — it’s terrific. The author develops several interesting characters, shifts the story effortlessly between the pre-, immediately post-, and many decades post-flu periods, and strikes just the right tone when describing how humans live in a world without running water, cell phones, internet, electricity, cars, jets, or countries.
They do more than just survive — that’s what makes the book interesting, plausible, and, despite the grim plot, at times quite uplifting.
And, for the record, it has no embarrassingly incorrect medical information, though one might wonder at times how influenza could have a nearly 100% case fatality rate.
Small matter — it’s fiction, after all.
September 7th, 2015
Two Drugs with High Prices — One is (Surprise!) Good Value, The Other is Truly a Rip-off
By now, the fact that HCV treatment carries a high price is a fact as well known to the medical and non-medical public as 1) a million dollars doesn’t get you much in Manhattan or Bay-area real estate; 2) a Rolex is an expensive way to know what time it is; and 3) even though a Tesla doesn’t need gas, buying one won’t save you money.
But you know what? Something interesting has happened since the initial sticker-shock of the $1000/day pill and the cries of injustice from patients, the medical community, and activists. First, the price has been aggressively negotiated, and now is substantially lower — various unofficial estimates suggest the actual cost is around 50% of the wholesale acquisition cost. Still high, yes, but much less than the dizzying cost of HCV treatment during the “SIM-SOF” days in early 2014.
Second, a careful analysis of this miraculous therapy shows it’s actually decent value. In other words, you pay a lot, but you get a lot too — this is what the cost-effectiveness literature shows (several citations in bullet number two at this link), and the public is starting to take notice. An editorial last week in the Times got it right (though it could have used a bit of quick medical editing, which I’ve provided):
The benefits of these new drugs are undeniable. They can essentially cure [not essentially cure — they do cure] the infection in eight to 24 weeks… Curing the patient decreases by more than 80 percent the risk of liver cancer, liver failure and the need for a liver transplant, thus saving money in the long run. Successful treatment can also greatly reduce the number of new cases of hepatitis C by preventing transmission of the virus through needle-sharing among drug addicts infected with HIV [HIV has nothing to do with it]… the Institute for Clinical and Economic Review, previously a skeptic, estimated that a likely course of treatment with Harvoni would make it a high value for individual patients and for most health care systems.
The editorial goes on to recommend lifting restrictions on treatment, in particular for those who don’t have advanced liver disease. This makes all kinds of medical sense, and will be great comfort to those of us battling with payors to get treatment to people before they have irreversible liver damage from HCV.
Meanwhile, one of our relatively obscure antimicrobials — pyrimethamine — has suddenly become staggeringly expensive. Used as part of treatment of toxoplasmosis (in particular for patients with AIDS), and rarely for malaria, pyrimethamine has been around for decades. A single pyrimethamine tablet, previously $13.50, now costs $750 — that’s a more than 50-fold increase.
It’s not as if new research funded by industry has found some novel indication for a previously underused drug. Nope, this is pure monopolistic pricing — in mid-August, a company purchased the rights to pyrimethamine, becoming the exclusive US distributor. As with the colchicine saga, this exclusivity allows them to dramatically drive up the price because, well, they can.
In short, sometimes you get what you pay for — and, at least in the case of pyrimethamine, sometimes you don’t.
Hey, this video doesn’t cover treatment, but it sure is funny!
[youtube http://www.youtube.com/watch?v=U9MU-FxsKRg?list=PLoeuxutUxJnkmhX6Rw9mBf_dDEkEy4-VH]
August 30th, 2015
(Not) Doing the Retinal Exam, and the Importance of Acknowledging Limitations
This past week, the New England Journal of Medicine released one of its excellent instructional videos, detailing how to do direct ophthalmoscopy to examine the retina.
That’s the use of one of those hand-held gizmos — an ophthalmoscope, see picture on the right — to look at the back of the eye.
As usual, the video was clear, succinct and professionally done. A great resource for clinicians, young and old.
But here’s a confession — the video could be a nominee for this year’s Oscar for Best Picture, it wouldn’t help me a bit. Because I’m absolutely horrible at this procedure, always have been.
I’m as likely to see something important in someone’s eyes using an ophthalmoscope as I am using a shoe, an avocado, or a tennis racket (to choose three random things that happen to be in the room right now as I write this).
The inability to do a particular part of the physical examination creates some uncomfortable moments, in particular during medical school when learning the skill. Asked to acknowledge that yes, we do in fact see/hear/feel what we’re being taught to see/hear/feel, medical students face a dilemma when failing to do so. In essence, there are three options:
- Tell the truth: “I can’t see the venous pulsations” — and ask the instructor for more guidance right there on the spot.
- Lie: “Oh yeah, the optic disc margin is sharp” — this gives the teacher a sense that you’ve mastered the technique, but it’s basically cheating and a very bad idea in clinical medicine, for innumerable obvious reasons.
- Silence: Be quiet on the matter, blending into the background and allowing the class to move on — and remain hopeful that you’ll pick up the skill later with more practice.
I wish I could say I had the maturity to go with #1, but in fact #3 was the route I chose.
Even if I had chosen #1, however, I’m not sure it would have made much of a difference. The reason I can’t do this procedure is because my own eyes are so bad — which, for a variety of reasons having to do with the optics of it, make direct ophthalmoscopy virtually impossible.
Trust me on this one — it’s not just an excuse. (Of course it is.) The right eye is particularly useless, which means I’d have to use my left eye to look into a patient’s right eye. If you imagine doing this, it sets up a very uncomfortable nose-to-nose encounter with your patient — highly unhygienic and socially weird, a reason right there not even to try it.
In the face of limitations we have as doctors, we invariably come up with rationalizations to make ourselves feel better. And here are mine about this particular deficit:
- Visual complaints are serious business — wouldn’t this deserve a referral to a real pro, an ophthalmologist? You can be sure that in the CMV retinitis days, my threshold for referral was very very low.
- Similarly, let’s say I found something incidentally on ophthalmoscopy — certainly this would warrant having an ophthalmologist see the patient to confirm, right? What non-eye doctor would be 100% sure saying that what they visualized with their crude scope is benign?
- Direct ophthalmoscopy isn’t even the best technique to look at the retina — the indirect method is far superior, preferred by all retina specialists.
- There are many other things in medicine I can’t do (replace heart valves, biopsy colons, do immunohistochemical stains, interpret EEGs, remove thyroid tumors) — this is just one more.
- I may not be able to see someone’s retina (especially their right retina, see above), but I’m pretty good at listening to heart murmurs, if I do say so myself. Hey, I once noticed that a patient with endocarditis developed aortic insufficiency before the cardiologist did. Granted, she hadn’t seen him that day yet, but still …
In all seriousness, the real reason for this confession is that I’m pretty sure we all have limitations. Why else would the orthopedists consult us ID doctors for essentially every infectious complication on their patients, no matter how simple? After all, before their residency, these pre-orthopods were some of the smartest medical students — did they suddenly lose their brains when they began doing knee replacements?
Not a chance. It’s simply that at some point, it makes much more sense to acknowledge these limitations — and move on — than to pretend they don’t exist, or even worse, to fake it.
Paul E. Sax, MD
Contributing Editor
NEJM Journal Watch
Infectious Diseases
Biography | Disclosures | Summaries
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