Recent Posts

October 10th, 2022

Molnupiravir Results in PANORAMIC Study — It’s Not All Bad News

Last week, the large PANORAMIC trial of COVID-19 treatment in outpatients with mild-moderate disease appeared in a pre-print. This large (25,783 participants!) randomized, open-label study compared molnupiravir vs. usual care in adults 50 or older, or having comorbidities known to make severe disease more likely.

The results?

Four days faster recovery with treatment! You might think this would be welcome news.

Ah, but think again. Because the response from the ID cognoscenti was lukewarm, and that’s putting it kindly.

Many cited the study’s open-label design as a major limitation, negating the favorable time-to-recovery result. The placebo effect is certainly in play when a person knows they are receiving active treatment.

Some noted the ongoing concerns with molnupiravir and mutagenicity — and the theoretical worries about generating variants.

Others criticized the cost of the drug.

But the major theme of the naysayers emphasized the inability of the treatment to demonstrate a benefit in the primary endpoint of interest — hospitalization or death. Here the result was quite low for both arms, and equal, at 0.8%. Not a bit of difference, and this lack of efficacy is also what the headlines typically featured.

As a result, when I polled people on whether they would prescribe molnupiravir now that they know the results, it didn’t surprise me that a majority said no.

With the caveats that this sort of poll is only representative of the people who saw and answered it, and that Twitter can be a really negative place — like “staying too late at a bad party full of people who hate you” — I do think it’s worth acknowledging these important concerns about both the study and the drug.

But it’s also worth highlighting the good news coming out of this trial — and it’s very good news indeed.

First and foremost, the amazingly low incidence of hospitalization or death underscores how much less severe COVID is now compared to when it first hit the human race. It’s especially notable since the study population included only those at risk for bad outcomes. When it comes to most infections, it’s a wonderful thing not to be immunologically naive, and the participants had very high rates of vaccination and/or prior infection.

(Parenthetically, the lower disease severity presents a virtually insurmountable challenge to conducting a clinical trial with this “hospitalization or death” endpoint — as noted by Dr. David Boulware, the sample size would need to be extraordinarily large.)

Second, let’s go back to the observed faster time to recovery for a moment. A 4.2-day improvement in time to recovery with no major short-term side effects  — or drug interactions — is nothing to sneeze at, if you’ll forgive the very apt cliche. As a point of reference, this is quite a bit more than the observed clinical benefit seen with oseltamivir and baloxavir for influenza, which is typically 1-2 days. Note also that there is no mention of clinical or virologic rebounds, though perhaps the researchers did not assess for these endpoints.

So let’s imagine you are a person with COVID. You’re miserable — feverish, sneezing, coughing, out of work. Not hospitalization-level sick, but feeling pretty lousy.

Your doctor tells you they have a 5-day treatment that, in a large study, shortened the time to recovery by 4-5 days compared to people who didn’t get the treatment.

Plus, there were no major side effects, and the amount of virus dropped faster, too.

Wouldn’t you at least consider it?

Or, as Dr. Sarah Scott writes:

Well said. While acknowledging that the open-label design makes ascribing this benefit solely to the drug is impossible — people really want to believe that their treatment is making them better — we can also note that this difference in time to recovery is substantial, even by the standards of other non-placebo controlled trials.

Finally, the PANORAMIC investigators deserve a ton of credit carrying off this very large, pragmatic clinical trial. We all look forward to seeing it go through peer review and revision, information about rebounds (if they happened), as well as the promised follow-up data regarding long COVID. Also, the results of the nirmatrelvir/r (Paxlovid) arm of the study promise to be particularly interesting, as this is way more widely used than molnupiravir for COVID treatment, at least here in the United States.

Meanwhile, enjoy this video, because I certainly did.

September 28th, 2022

Even if You Think “The Pandemic Is Over” — Let’s Make In-Person Meetings Safer

“The pandemic is over.”

Someone very famous used these words recently, triggering all kinds of controversy.

While most ID clinicians groaned at the comment, knowing that it would be taken out of context, repeated in headlines without any of the President’s cautionary statements, and fuel COVID denialists, it’s also worth acknowledging that most of the country really does feel this way.

Look, if at least 90% (rough estimate) of travelers at Boston’s Logan Airport no longer wear masks, either while waiting for their flight or on the plane, it must be 99% in most other U.S. airports.

(I checked with my colleagues in other cities. It is.)

Plus, schools are open, restaurants busy, concerts and sporting events full. Postponed weddings are happening. People again travel for business and academic meetings.

If we haven’t returned to prepandemic “normal,” whatever that is, we’re certainly heading that way. Why? Because you’d have to be a hermit if you either haven’t had COVID yourself, or don’t have several close family members or friends who’ve had it — sometimes multiple times — and recovered uneventfully.

“The flu I had a few years ago was much worse,” said one of my own friends this week, walking his dog in our neighborhood, and looking just fine.

In short, the infection remains incredibly common, likely will get most if not all of us eventually, and — here’s the fact — just isn’t as severe as it once was, mostly because of vaccines and prior infection-induced immunity. All these things are true.

This is the part of the post where I need to insert these critical and essential caveats. Some people still get quite sick from COVID — I worry in particular about those with weakened immune systems. Some people will get long COVID. And testing positive is still enormously disruptive, forcing people into isolation and wreaking havoc on schools, workplaces, daycare centers, and many carefully planned events. In short, COVID still s–ks.

You can quote me on that. Colds, flu, RSV, and company are pretty lousy too.

But as part of the improvement in the prognosis for COVID, and the opening of our society (even for ID docs) to multiple activities that previously had been cancelled, I want to address one in particular — and that’s in-person meetings.

We can’t make them 100% safe. Can we at least make them safer?

So far I’ve traveled to three, and of course my colleagues have started doing the same. IDWeek is coming up in October, CROI in February, and these meetings will undoubtedly include many meetings and unmasked social interactions that could spread both COVID and other respiratory viruses. I get that.

But mitigating strategies are still welcome. One such meeting at IDWeek specifically cited that it would take place in a room “that has accordion doors so it can be opened up for airflow, as well as a wrap-around balcony.” Terrific. Ventilation is good — it’s one of the major lessons learned during the pandemic.

Another meeting asked us to do rapid antigen tests on arrival. No, these tests aren’t perfect, and they don’t screen for other respiratory viruses, but the positive predictive value of them is high. I’d welcome a cluster randomized trial of testing vs. no testing prior to in-person meetings.

So let me share an example of what not to do, “pandemic is over” notwithstanding.

I recently went to a meeting of other ID specialists, and planned ahead of time to be unmasked during both the meeting and the lunch. I figured we ID docs would not attend if we had a respiratory illness. We’ve gotten good at that, avoiding illness “presenteeism,” and most people with contagious respiratory viruses have symptoms. So that was some reassurance.

But here’s the not-OK part: The meeting took place in a tiny, crowded, low-ceilinged room, with barely a few inches between seated participants — the very converse of “social distancing.” If someone had one of those CO2 meters placed strategically in the center, I suspect it would have been sounding its alarm from the first 30 minutes.

The room was small enough that multiple people commented about the forced intimacy, making jokes about how ironic it was that we ID doctors would be sharing so much mutual air over the next several hours — especially because it was a beautiful fall day. “We should have the meeting outside,” said one of the organizers. Ha ha.

Yep, it was packed in there — if not quite phone booth stuffing or Marx Brothers-stateroom tight, certainly much more crowded than any meeting room I’d been in for years. Let’s just say it’s a good thing we all showered after our morning run or time on the elliptical, because any hygiene infractions would have been immediately evident. Lunch, fortunately, was in a much larger, well-ventilated room.

So I wore an N95 mask during the meeting. I was the only one.

Because COVID still s–ks.

https://youtu.be/NWFl2S5-Ua0

September 8th, 2022

A Back To Work ID Link-o-Rama

Zelda, Zoe, and Louie on the cover of their latest album, Parallel Paws. With apologies to Debbie Harry and Chris Stein.

A few nuggets are rattling around in the inbox post Labor Day, including this extraordinary photo of our family dogs Zelda, Zoe, and Louie, posing for their latest album cover.

Woof!

Besides, I haven’t done one of these Link-o-Ramas since January 11, 2021! That was either 20 months ago or 20 years, hard to keep track of time these days.

Enough with the introduction. On with the links — starting with some highlights from this year’s 2022 AIDS Conference in Montreal:

Non-ID section:

 

Seems particularly appropriate for us ID doctors, as we gradually return to in-person big public meetings.

(Dog photo by Hollis Rafkin-Sax, edited by Anne Sax, based on a design idea by … me.)

August 16th, 2022

Story as Evidence — Our Story

Edvard Munch, Towards the Forest II, 1915.

JAMA has a long-running and quite wonderful weekly feature called A Piece of My Mind, in which clinicians (mostly physicians) write about the human side of medicine. Not the place for dry descriptions of study designs or laboratory methods, A Piece of My Mind instead welcomes anecdotes, opinions, and emotions.

After all, as Drs. Preeti Malani and Jody Zylke wrote in a 2020 piece celebrating 40 years of the column, “physicians treat patients, not just their diseases, and confront complicated issues and circumstances daily.” In many of the columns, the table is turned, and the physician-writer shares what it’s like to be the patient — the person on the other side of the stethoscope, the scalpel, the chemotherapy infusion, or the psychotherapist’s office.

There’s a real strength to this form of communication, which at times can exceed the influence of even the best-designed clinical trial. While a single case might not stand up to a rigorous statistical analysis, a compelling story about a single patient — either as the caregiver or the person receiving the care — can have remarkable power.

Dr. Louise Aronson brilliantly described this phenomenon in a 2015 submission entitled “Story as Evidence, Evidence as Story.” She wrote:

In the public arena, the N-of-1 personal experience is considered not only data worthy of consideration but also sufficient to establish expertise. With a frequency and consistency that should make those who question the role of anecdotes in discussions of medicine and science rethink their position, a single, well-told story of human suffering trumps the most eloquent explanation of a large-scale trial.

I thought of this “Story as Evidence” phenomenon when hearing that the Supreme Court overturned Roe v. Wade, which eliminated the constitutional right to an abortion after nearly 50 years. Naively, I thought growing up that this right to choose would never be taken away.

Why is this relevant to A Piece of My Mind?

Because my wife and I have our own story to tell, now more than 2 decades old, and JAMA was kind enough to publish it this week.

August 8th, 2022

Long-Acting Injectable HIV Therapy for People Who Won’t Take ART?

Atlas. Lee Lawrie and Rene Paul Chambellan, 1937.

HIV treatment is so spectacularly effective that you might be surprised to hear that some people with HIV still have uncontrolled viral replication. We HIV clinicians watch with frustration and sadness as they experience progressive immunodeficiency, complications from advanced HIV disease, hospitalizations, and HIV-related deaths. Plus, while viremic, they continue to risk transmitting the virus to others.

What’s the barrier to successful treatment? In 2022, it’s almost never drug resistance. It’s that they can’t, or won’t, take oral antiretroviral therapy. Excluding those completely out of care (that’s a different problem), I’d estimate from various studies that they typically represent around 5% of a clinic’s population.

The percentage with uncontrolled HIV is higher in places like Ward 86, the safety net HIV clinic at UCSF — around 15% by their estimates. True to its mission, the clinic serves many people struggling with poverty, substance use disorder (especially cocaine and crystal methamphetamine), unstable housing, psychiatric illness, and low medical literacy. That’s why the case series they just published using long-acting cabotegravir and rilpivirine (CAB-RPV) is so remarkable.

That’s right — cabotegravir and rilpivirine for this highly challenging patient population, a group most certainly underrepresented in the pivotal clinical trials ATLAS and FLAIR.

Out of 132 people in Ward 86 referred for CAB-RPV treatment, 51 started injections. Of these, 39 patients had at least two treatments and were included in this report. The good news:  All those with virologic suppression at baseline maintained HIV control during the follow-up, a tribute to the enhanced care provided by the team of clinicians involved in the program.

But by far, the most notable aspect of this report is what happened to the 15 people who were not on suppressive ART — in other words, the group highlighted in the first paragraph of this post, those not taking their meds.

This viremic group had a median CD4 cell count of 99 and a viral load of around 50,000 (with one over a million); a patient with resistance to raltegravir and elvitegravir (harboring the N155H mutation) was also treated. Despite these unfavorable baseline characteristics, 12 of 15 achieved virologic suppression (including the person with N155H), and the other 3 have HIV RNA that has declined by more than 2 log.

Wow.

These exciting results notwithstanding, it deserves emphasis that using CAB-RPV for viremic patients takes us way outside the indications outlined in the FDA approval. This specifically stated that the treatment is for those “who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine.”

There are plenty of additional caveats about using CAB-RPV in people not taking oral ART. The study includes just a small number of viremic patients, and the follow-up is relatively short (less than a year). We can’t say whether virologic suppression will be maintained, or what proportion will drop out of care and miss their injections, or how many will develop the much-dreaded two-class drug resistance to both integrase inhibitors and non-nucleoside reverse transcriptase inhibitors — resistance that will make subsequent treatments much more challenging. Plus, payers in some regions may not be as generous in covering treatment for a non-FDA approved indication.

It’s also worth remembering that Ward 86 is a special place, hardly representative of most HIV, ID, or primary care clinics. They have tons of dedicated on-site resources to enhance the care of their difficult-to-reach patient population. This includes doctors, nurses, pharmacists, social workers — a veritable army of people available to support and chase down people who might go astray while on HIV therapy.

Example:  Two of the patients in this report with unstable housing received injections in the community with “street-based nursing services.” (When I wrote “chase down,” this is what I meant.) How many of us HIV providers have access to this kind of wraparound care? In other words, if you’re in a standard ID or HIV clinical practice, don’t try this at home quite yet.

These caveats notwithstanding, I maintain that this novel use of CAB-RPV is highly important, and that it’s critical it be explored further. Up to this point, our options for people who won’t take oral ART have been highly limited. In desperate cases, we’ve even resorted to feeding tubes to administer ART, these placed during prolonged hospitalizations for AIDS-related complications. If CAB-RPV can provide even half the people who won’t take oral ART an effective option, use in this population will be save more lives than CAB-RPV will through its FDA approved indication. After all, those people are by definition doing well on ART!

The alternative to trying this might be an HIV-related death. And no one in 2022 should die of AIDS without our doing everything we possibly can to get them on antiretroviral therapy.

Even if that includes an unapproved use of cabotegravir and rilpivirine.

July 22nd, 2022

The Paperwork Demands for Academic Medical Teaching Are OUT OF CONTROL

Playing at Bubbles, Piercy Roberts, 1803.

Why all caps in the above title? It’s to call attention to a problem that’s getting worse each year in academic medicine, especially when it involves teaching or talks.

The requirement to submit a veritable truckload of forms, documents, attestations, and summaries, all due months before the actual event.

Let’s explore in more detail what this might involve — and I assure you, what is outlined below is no exaggeration.

After accepting an invitation to teach, give medical grand rounds, or visit an academic medical center, you might receive an email from a “person” with an anonymized email such as  “Internal Medicine Administrative Services” or “Medical School Education Coordinator.”

You know those emails that you dread to open because they have so many attachments that you barely know where to start?

Some of these emails have four or more attachments, plus additional secure links (which may ask you to create usernames and passwords), and numerous deadlines for all the required documents. Can an email weigh a lot? If so, these email behemoths are comparable to the Wile E. Coyote’s anvil on the Road Runner cartoons, the 16-ton weight from Monty Python, or Laurel and Hardy’s pianos.

If such emails fill you with dread, it’s because of the Fifth Law of Thermodynamics — otherwise known as Sax’s Law of Email Avoidance:  A person’s reluctance to open an email and deal with it promptly is proportional to the square of the number of attachments. Example:  An email with four attachments is 16-times more likely either to sit unopened and/or not get completed efficiently than one with only a single attachment.

Now let’s review the required items:

  1. Last name, first name, degree(s).
  2. Hospital and academic titles.
  3. Head shot. When submitting this photograph, those of us of a certain age might be tempted to choose something from a couple of decades ago. Fountain of Youth.
  4. Presentation title and date. It’s slightly annoying that all of this information from these first four items is either already known to the inviters (certainly the date) or available via a simple web search, but I’ll grant them these requests as we’re just getting started.
  5. Updated Curriculum vitae. Got to check those qualifications!
  6. Abbreviated biography. These are those braggy paragraphs that a person writes to help with introductions. Maybe I’ll include the fact that I won an essay writing contest about yogurt several decades ago for Boston’s Real Paper — or was it the Boston Phoenix? — allowing me to be on a panel of taste testers to identify Boston’s best brand. Or that I listed in my college yearbook that I was a member of a club called the “Leverett Luggage Society,” a club that did not exist.
  7. PHI query and permission form. PHI stands for “Protected Health Information,” meaning identifying information about patients. If any of this information is in your talk, it will require an additional signed form from the patient. Note to teachers everywhere — unless absolutely necessary, try not to include PHI in your talks. Seriously. Just not worth it. You can use a case-based approach to teaching, but modify the case sufficiently so that it does not include identifying information.
  8. Three (sometimes four) learning objectives. Before submitting these, you could be referred to “OCME requirements” for guidelines on how to write good Learning Objectives — these might come on a separate attachment — or you could be referred to the OCME web site. “OCME,” in case you’re wondering, stands for Office of Continuing Medical Education, not Office of the Chief Medical Examiner, or Orange County Model Engineers. The last of these, I’ve learned, was founded in 1977 and offers free rides on trains that operate like real locomotives, but are 1/8 the size of the real thing. See what can be learned from a quick web search? And before going on, I could write an entire post on these “learning objective” requirements which, as I’ve noted before, rarely lead to more learning, but sure are annoying to write.
  9. OCME disclosure of relevant financial relationships. Every talk requires this information — it’s a list of potential conflicts of interest — but despite the universality of this requirement, there are as many different forms for this information as there are stars in the sky — like snowflakes (to shift metaphors), no two are alike. How about all these Orange County Model Engineers hop off their mini-trains and come up with a standardized form? For a while I just submitted a Word document that listed potential conflicts of interest, and wrote in caps on all the proprietary forms — “SEE ATTACHED DOCUMENT.” That worked for a while, but nobody accepts that one anymore.
  10. OCME mitigation of relevant financial relationships. And if you do have some relationships, you will need to fill out an additional form, one which includes multiple questions (often as many as a dozen) to satisfy the organizers that these potential conflicts can be resolved. Here’s an example, taken from a recent form: “If I am discussing specific healthcare products or services, I will use generic names to the extent possible. If I need to use trade names, I will use trade names from several companies when available, and not just trade names from any single company. My learning objectives may not include trade names. (Check Agree or Disagree.)” Easy for me — I’m one of those nutty ID docs who says “trim-sulfa” rather than Bactrim, “cephalexin” rather than Keflex, and  “pip-tazo” instead of “Zosyn,” both because I hate using trade names (especially when the drug is long off-patent), and because the last one always reminds me of Led Zeppelin’s 4th album, which is distracting.
  11. A list of references, and a PDF of a relevant published paper. If you’re really unlucky, there will be a requirement for an annotated bibliography, explaining why this paper was selected for this talk — oh the pain. For medical schools out there reading this post, please don’t get any ideas. “PDF,” by the way, stands for Portable Document Format, not Probability Density Function, or Pigs Do Fly. Just so you know.
  12. Speaker agreement form.  This includes permission for use of your image in pre-talk announcements, as well as miscellaneous photographs, audio, and video taping. Of course it needs a signature — one of many documents in this bundle that needs a signature, even though all this stuff flies around electronically, and “e-signing” different forms presents its own form of digital torture.
  13. Four “board-style” multiple choice questions related to the talk material. If the course organizers are in a particularly demanding mood, they might ask you also to ensure these questions specifically linked to the dreaded Learning Objectives, see item #8. And yes, careful readers coming back here to re-read this list of required items might note this one was added late — I no doubt left if off originally since crafting good “board style” questions is particularly challenging, time consuming, and painful. Subconsciously I’ve been so annoyed by this request that I couldn’t bring myself even to write “board style” questions.

I realize that these requests are not the fault of the conference organizers or education coordinators — they are responding to requirements issued by others, usually medical schools or accreditors. Anyone who runs a post-graduate course feels this pressure, including me.

But wow, is it ever a disincentive to teach.

OK, I’ve complained enough. Now it’s time for a solution to this quagmire.

How about this approach, which was taken by a very kind person who invited me to give a lecture earlier this year?

Hi Dr. Sax, hope you’re well. We’re planning our annual conference this year, and would be delighted if you would be one of our speakers on [insert ID topic here]. Don’t worry about paperwork — we’ll take care of it — just provide us the talk title and a list of your financial disclosures, if any. We’ll also send you some proposed learning objectives for your review and approval a few weeks before the conference.

Thank you for considering!

Ellen

And thank you, Ellen, for making it so easy! And for the record, your email was light as a feather.

July 1st, 2022

Fellowship Transition and Developing a Sense of Belonging

Always a good time for a cute puppy picture.

It’s July 1, which means that today, or sometime very soon, many internal medicine residents will transition to becoming subspecialty fellows.

There are many appropriate words to describe this change, including exciting, nerve-wracking, and challenging, but one that doesn’t get quite enough attention is how strangely lonely it feels. The reason this sensation occurs is because medical residencies — through their size, structure, and voluminous shared experiences — engender a powerful sense of belonging. The bonds between you and your co-residents are strong indeed, especially after three years together.

Fellowships can’t instantly create this comforting feeling. Your fellowship group is smaller. You typically work alone, with an attending, and not as part of a team. Plus, there’s the disquieting experience of having mastered something (the bread and butter of inpatient clinical medicine), only now to be plunged into the uncertainties of a specialty that you haven’t yet learned.

How many incoming ID fellows are more comfortable managing chest pain than postpartum fever? I’d estimate it’s 100%.

If one adds to these factors the geographic relocation that may occur, it’s not surprising that subspecialty fellows take some time to feel really part of their new tribe.

Proof that the bonding of medical residency takes time to wear off is that most fellows spend the first part of their fellowship using the word “we” to describe their residency group, not their fellowship.

Here’s a smattering of select phrases that might be heard during the first few months of ID fellowship:

We used ceftriaxone and doxycycline, not azithromycin.

We would do the thoracentesis ourselves.

We don’t use procalcitonin, it’s not reliable.

And of course, the classic (and inevitable):

We would never consult ID on a case like this.

I completely get it and went through the same thing as a first-year fellow. I distinctly remember telling an inpatient medical team that their choice of antibiotics for spontaneous bacterial peritonitis was wrong — because “we” did it differently during my residency. A residency done at a different hospital, of course.

(For the record, it wasn’t wrong. It was just different.)

So to those of you making this transition, we (meaning the ID community) totally understand how you’re feeling. We want you to feel welcome and part of our ID world. It might take a little time, but you’ll get there.

Pretty soon, you’ll start saying “we”, and when you do, you’ll mean you and other ID docs like you. I promise.

Welcome to the club.

June 21st, 2022

Mayo Clinic Study on Paxlovid Outcomes is Reassuring — but Likely Underestimates Rebound Rate

Filippo Balbi, Testa Anatomica, 1854.

Over at Clinical Infectious Diseases, researchers from the Mayo Clinic published a retrospective analysis of nirmatrelvir/r (Paxlovid) treatment, with a careful review of each patient’s chart.

The goal was to determine the clinical outcomes after the 5-day treatment course, with a focus on the frequency of rebounds — a topic of great clinical interest but with little real-world data with a decent-sized denominator.

The study included 483 patients with at least some risk factors for severe COVID-19 based on the institution’s Monoclonal Antibody Screening Score. Adjudication of eligibility was done centrally through the hospital’s COVID-19 outpatient treatment program. The mean age was 63, and 93% were vaccinated. Patients were given the option of telemedicine follow-up and encouraged to self-report symptoms or other problems; this information and their full electronic medical records were reviewed after the treatment.

Out of this group, 4 (0.8%) clearly experienced clinical rebound — these cases are described. None of the 4 received re-treatment or were hospitalized. Two other patients (neither of them rebounders) did require hospitalization, but the authors note these were unrelated to COVID-19. There were no deaths.

We can be reassured by the information on the low rate of severe outcomes, an outcome mirrored in low hospitalization rates nationally despite lots of ongoing cases. Rates of hospitalization for each COVID-19 case are now extremely low, especially among those vaccinated, and observational studies (peer-reviewed and published and unpublished) suggest that Paxlovid may reduce this risk even further. A large retrospective study from Kaiser Permanente Southern California involving 5,287 patients found similarly  low hospitalization rates.

(Note that these observational studies include patient populations treated with Paxlovid with established risk factors for COVID-19 adverse outcomes — that’s how it’s mostly prescribed under the Emergency Use Authorization (EUA). By contrast, those enrolled in the EPIC-SR study, which was recently stopped due to futility, were “standard risk”. Critically important will be information on baseline characteristics in EPIC-SR.)

For the Mayo study, the authors are to be credited for collecting and reporting the data so quickly, especially at a time when clinicians and patients increasingly observe the rebound phenomenon and wonder what to do about it. The centralized program used for distributing COVID-19 treatments is an additional strength of this report, as it allowed participants the opportunity to self-report progression of symptoms, and upfront ensured that all who were treated met the criteria for high risk based on the EUA.

The big limitation of this Mayo study, however, is that it’s retrospective. As a result, I strongly suspect the 0.8% rate of rebound substantially underestimates the true incidence. Pfizer reported rebounds in 2% of study participants in the prospective EPIC-HR trial, a rate more than twice as high. Based on anecdotal experience — there’s lots of Paxlovid treatment out there! — I would not be surprised if it’s at least 10 times this high, or in the 5-10% range.

What still remains unknown, frustratingly, is whether treatment with subsequent rebound reduces — or paradoxically increases — the total amount of time that people are contagious, or, if the total time is the same, does it just delay the time that a person can confidently say that they’re in the clear?

Why is this important? I’ve had people tell me that they don’t want to take the drug because they’ve heard it might lengthen the time they’re contagious. And I’ve had other patients who experienced rebound express regret on having taken the drug — even though we have no idea whether they would have tested positive for a prolonged period even without the treatment.

Let’s hope further data from prospective studies give us some answers — in particular, the placebo-controlled trials, either Pfizer’s two studies or the large PANORAMIC trial done in the United Kingdom.

In the meantime, I’m still advising people at higher risk for COVID-19 adverse outcomes — even if vaccinated — to be treated with Paxlovid, uncertainties about the above issues notwithstanding.

June 6th, 2022

Still More Fun with Old Medical Images

Back in the Before Times, this site would occasionally dabble in lighter fare:

https://twitter.com/buitengebieden/status/1533022340887486466?s=20&t=ShPbhfDhg-BwCP2bWisXfA

And, the subject of today’s post — Fun with Old Medical Images.

Here’s how it works: We display an old medical image — something with long-expired copyright protection to reassure my editors and keep me out of trouble. Then, through the magic of the internet, I give it a fresh caption and a brief commentary. It may or may not have an ID theme.

Surprised that something with the NEJM Group imprint would stray into such territory, you will then smile at the incongruity and maybe even laugh a little. All for the usual bargain price of this fine content.

(We accept all major credit cards, PayPal, and cryptocurrency. And, I’ve been told, your purchase is FSA-eligible for reimbursement.)

Off we go with #1 — always good to start with an ID one:

“And this here, Miss, is why I’m going to get my N95 mask.”

Could it be TB? It can always be TB. Better take precautions!

Now, for #2, a grim visitor — or is it?

“Didn’t you say you wanted a cup of sugar?”

Don’t judge a book by its cover — or more accurately, don’t prematurely judge a scary skeleton handling an hourglass as a portent of death. He’d heard you needed a kitchen staple and is just being neighborly!

There’s plenty of time to finish baking that cake before the scythe deals its final blow.

Let’s stay (roughly) with this time period — early 19th century, according to my crack research team — with #3:

“Thorsten, time to check again on that prior authorization for semaglutide.”

Ah, the travesties of insurance coverage and prior authorizations — a problem even in 19th-century England, I guess!

Please note the tried-and-true humor technique I used there, mixing the old image with a modern concern. Yes, it’s easy, but remember — these are Old Medical Images. And I’m not that old. Never saw this one in medical school, for example.

Let’s get fit with #4:

Gertrude didn’t consider it a full workout until she’d completed at least 30 minutes on the automated Exer-Master.

Well of course she didn’t consider it a full workout — that side-saddle mount looks mighty comfy, and the powerful Exer-Master® engine is doing most of the work! Get this person a Peloton! Then she’ll know the meaning of “exhaustion for those with disposable income.”

For #5, we’ll visit a commonly done test on inpatient medical services everywhere:

The medical team was pleased that the patient easily passed his swallowing study.

No mechanical soft solid diet for him! And don’t make the “have a frog in your throat?” joke — he’s sensitive about that.

Let’s finish with #6, a more modern, “hip” offering, hip in more ways than one:

A little golf. A little oil painting. Later — a slimmer figure!

Don’t take our word for it. Pony up your $3.88 for Item 56 F 5965inflatable sauna shorts — and you too can knock inches off your hips and belly!

Comes in a wide range of colors never before seen in nature.

That’s all for today, folks. If you’ve read this far, I hope you’ve enjoyed this latest installment of Fun with Old Medical Images. And, if not, we’ll be back with more grim pandemic news next time.

Chicken!

May 23rd, 2022

In Praise of Dr. Glaucomflecken

In the Ophthalmologist’s Office, 1930. William Sharp.

Sometimes there is someone so good at something that there is universal agreement we are witnessing something special.

Babe Ruth, Serena Williams, and Michael Jordan competing at their peaks. Charles Dickens or Jane Austen creating whole worlds out of invented characters and plots. Vladimir Horowitz performing Rachmaninoff at Carnegie Hall. Bernini creating sculptures from cold, hard marble that still take our breath away when we see them for the first time, 400 years later. Velazquez featuring himself and other onlookers in the greatest painting of all time (OK, my opinion), Las Meninas.

And, in the category of “Creator of Short Satirical Videos about the American Healthcare System,” we have Dr. Will Flanary, more commonly known by his stage name, Dr. Glaucomflecken.

Unlike my crowning the Velazquez painting the greatest ever, I’d argue this one is not just my opinion. It’s a fact.

Flanary’s short videos — featuring him (and just him) playing a variety of doctors, nurses, and administrators — have earned him universal praise from the medical community. We gobble up each release on Twitter or TikTok or YouTube, and rapturously respond with recognition about the eccentricities of our specialty, or the absurdities of American medicine. Often both.

How did a private practice ophthalmologist in Portland, Oregon, become the universal spokesperson for frustrated clinicians everywhere? As noted in a recent profile, he was always funny — doing stand-up comedy before medical school, contributing to a satirical medical site, posting on Twitter.

Then he nearly died — literally — suffering ventricular fibrillation at home in May 2020. Fortunately, his wife performed CPR until EMTs arrived, and he underwent placement of an implantable defibrillator during a short hospital stay.

But this experience didn’t only leave him with a lifesaving device. It also gave him first-hand experience navigating the insane complexities of the U.S. healthcare system, one so Byzantine that people who move here from Canada or Europe shudder at the prospect of dealing with it. Flanary took out his frustrations by skewering the system in his short videos, which have a gargantuan following.

Some choice examples: Prior authorizations. Hospital budget cuts. Academic publishing. The medical residency match.

How popular has he become within the medical community? He has over 1.5 million followers on TikTok, more than half a million on Twitter — that’s a lot. He’s the commencement speaker for today’s Yale School of Medicine graduation, quite the honor! I’m hoping to interview him for our inaugural podcast on Clinical Infectious Diseases, but not sure he will have the time — the invitation is currently sitting in his email inbox.

However, maybe he ultimately will agree to the interview, because he seems to have a soft spot for our quirky specialty. In these videos, watch him quite brilliantly capture our penchant for obsessive histories, long notes, and responsible antibiotic prescribing — and never once does he make fun of us for not doing any surgical procedures. Enjoy!

1. Medical student arrives for his ID rotation.

2. Ace your interview for ID fellowship.

3. How to think like an ID doctor.

4. … and let’s finish with a timely one.

 

 

HIV Information: Author Paul Sax, M.D.

Paul E. Sax, MD

Contributing Editor

NEJM Journal Watch
Infectious Diseases

Biography | Disclosures | Summaries

Learn more about HIV and ID Observations.