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August 12th, 2018

Apologies, Our E-Mail Notifications Are Not Reliably Going Out

Last week, I wrote something I really wanted my long-time friend and colleague, Susan Larrabee, to read. Susan is the HIV social worker-extraordinaire I’ve been working with for a million years, give or take a few.

The piece covered how rewarding it is to care for people with HIV. If anyone could affirm that view, it’s Susan. She’s the kind of cherished colleague who provides an instant antidote to burnout. If you’re working with someone like that, lucky you!

But here’s how our conversation went when I popped into her office looking for her approval:

Me (hopefully):  So what did you think of that piece?
Susan:  What piece?
Me (trying to hide my disappointment):  The one I wrote on my blog — you know, on caring for people with HIV. Thought you’d really enjoy it.
Susan: Didn’t see it. And I was wondering — why did you stop writing your blog? Too busy?
Me (annoyed):  @#$%&!

(Those punctuation marks, by the way, are called a grawlix — used to represent expletives or swearing in comic strips. Now you know.)

The reason Susan thought I’d stopped writing the blog is because we’re having technical issues here at NEJM Journal WatchOur reader email notifications aren’t reliably going out when there’s a new post. For some of you, that’s the only way you know when there’s something written here.

For example, Susan. For all her brilliance regarding human emotions and motivational interviewing techniques, she would be the first to admit she’s technically challenged. She is as likely to subscribe to an RSS feed as she is to hack the operating system on someone’s Tesla. She might not even know that a Tesla has an operating system.

(“What’s a Tesla?”, asks Susan.)

I feel bad about this problem of ours, since those of you who signed up for the email notifications took the time to do so — I’m very grateful to you for that.

But rest assured our technical team at NEJM Journal Watch is working behind the scenes to try and fix this “bug” — which, though not literally infectious, is at least non-communicable.

So thanks for bearing with us while we try to figure out what’s going on.

In the meantime, here are few other ways to be notified of the new posts:

  • Follow me on Twitter (@PaulSaxMD) You’ll get notification about all the posts that appear here, plus bonus information about ID, medicine in general, baseball, and dogs, among other critical topics. Making fun of #predatoryjournals is particularly fun on Twitter.
  • Follow NEJM Journal Watch on Facebook
  • Sign up for the Physicians First Watch daily newsletter — you should do that anyway, it’s great!

And here are two dogs who aren’t quite so sure about becoming vegetarians:

August 5th, 2018

Why Caring for People with HIV Is Still Great

Earlier this year, I wrote a piece about friends and colleagues of mine who have left HIV clinical practice. Something about it touched a nerve. It’s one of the most commented-on pieces in the history of this blog.

And this was a typical response:

Admittedly, it was kind of a downer — but it might have been slightly misinterpreted. A lot of the problems my friends cited could have easily applied to almost any area of clinical practice; these challenges were by no means limited to HIV care.

They mentioned the inscrutable and user-unfriendly EMRs, the lack of appreciation for cognitive specialties, the pain of “quality metrics” that require endless box-checking, the difficulties of funding care for the underserved. Safe to say that every primary care clinician in the country feels the same pain.

So, here’s a flip side to caring for patients with HIV, and it’s not just me resorting to the form that prompted my family to give me this T-shirt as a commentary on my sunny personality. I truly believe that HIV care remains an extraordinarily gratifying aspect of ID clinical practice. Which is why it’s critical that ID doctors continue to do it.

Here, in a bulleted list for clarity, are a bunch of things that make HIV care spectacularly rewarding:

  • You can save someone’s life. Antiretroviral therapy is miraculous. Every ID/HIV specialist has had patients with advanced HIV disease and multiple complications literally rescued from the jaws of death by these lifesaving drugs. If you’re a clinician who doesn’t do surgery, it doesn’t get better than this, folks.
  • You can really get to know your patients. You might be surprised given my youthful appearance (ha), but I’ve been doing this a long time. Fortunately, my career has included that breathtaking time in the mid-1990s, when suddenly we had effective HIV treatment. As a result, I’ve been following some of my patients for more than two decades. I know Brian’s favorite Dorchester restaurant since he moved from the South End, Felicia’s daughter’s name and what play she’ll be in this semester at college, Cliff’s excitement about this year’s Red Sox, how long Mark drives on his truck route each day, how Evelyn has never missed an episode of Grey’s Anatomy (there have only been 317), Ira’s struggles with his latest software release, and what vintage car Tony is working on in his shop. (And yes, I changed their names!)
  • You will care for an extraordinarily diverse group of people. Despite stereotypes, there is no “typical” person with HIV, just like there’s no “typical” person with most infectious diseases. They will come from every race, occupation, country, and tax bracket. Our clinic cares for patients in their late teens up to their late 80s; our oldest patient just died of non-HIV-related causes shortly after her 90th birthday.
  • You will continue to learn a lot about non-ID medicine. The aging of the HIV population forces us to keep up with all these interesting and common non-ID-related problems and issues — diabetes, hypertension, osteoporosis, atherosclerotic disease, cancer screening, neurocognitive decline, depression, venous thrombosis, chronic renal disease, atrial fibrillation. As a long-term patient of mine said to me the other day, “The HIV part is great. It’s all the rest of the stuff that I struggle with!”
  • The field is constantly changing — for the better. Although almost all of the patients who regularly attend clinic visits are virologically suppressed, HIV treatment is always evolving — there’s a constant push to make what’s already great even better. That patient who was successfully treated in 1998 with d4T, 3TC, and indinavir, suffering through neuropathy, kidney stones, and ingrown toenails (yes, that was a complication of indinavir), may well be receiving a single pill with none of these side effects today. Ongoing research is pushing toward long-acting therapies (a once-weekly pill? a shot every 3 months?) — and, potentially, a cure. I wouldn’t bet against either eventually becoming a reality, though admittedly the cure part is still a ways off.
  • The science of HIV prevention has never been stronger. As exciting as we find the information that people on suppressive HIV therapy cannot transmit the virus to others, imagine how this feels to our patients? It is wonderful giving them this news. It is both liberating and, just as important, helps diffuse some of the stigma that has stubbornly stuck to HIV ever since AIDS came on the scene in 1981. For people without HIV, pre-exposure prophylaxis (PrEP) is nearly as much of a game-changer. Will one of the HIV vaccines currently in clinical trials be the next advance?
  • Your expertise will be valued in both the outpatient and inpatient setting. While most people with HIV are healthy and followed as outpatients, there is still a significant and important amount of care done in the hospital. These include patients with opportunistic infections and cancers, as well as non–ID-related issues that may influence HIV treatment selection. The mix of inpatient and outpatient care brings a wonderful diversity to the experience.

So, for you ID doctors out there, please keep doing HIV patient care — it remains among the best things I do as a clinician, and I don’t expect that ever to change.

Until we have a cure, that is!

July 29th, 2018

Really Rapid Review — International AIDS Conference 2018, Amsterdam

The International AIDS Conference — or “AIDS 2018” — returned to Amsterdam for the first time since 1992.

It’s worth pausing, with gratitude, to remember that 26 years ago antiretroviral therapy consisted of three available drugs — zidovudine (AZT), didanosine (ddI), and zalcitabine (ddC).

All were marginally effective, with limited durability and significant toxicity. In fact, the big debate in the early 1990s was whether treatment of HIV before symptom onset was worthwhile at all.

We had no NNRTIs, PIs, or integrase inhibitors. Aside from recommending condom use and abstinence, we had no strategies to prevent HIV among sexually active adults.

Fast-forward to today, where the goal is to have everyone with HIV on treatment for both their individual benefit and to end the epidemic.

Gratitude indeed!

Here are some highlights from the meeting which took place last week, a Really Rapid Review© of important (or just interesting) studies that caught my eye. Apologies ahead of time for missing your favorite — as always, let me know in the comments section what I missed!

Amsterdam remains a gem, a marvelous city with distinctive architecture, great food, nice people, picturesque canals, and incredible museums. It was even better than the last time I was here — seemed cleaner, bustling but less congested (at least with car traffic), and decidedly less seedy. The fact that it was unbelievably hot didn’t deter many of us (including me) from biking around town, joining the throngs who regularly take advantage of the flat terrain and the extensive bike lanes.

But visitors beware — when it’s time to go home, the airport is a chaotic, crowded mess. The warnings to arrive 3 hours before departure time should not be taken lightly. I’d call the airport a zoo, but that might be insulting to some zoos!

Poor Melanie! Hartsfield will seem downright peaceful by comparison.

Next year’s meeting will be in Mexico City, July 21-24, 2019. It too is a wonderful, vibrant city (and where I’ve had some of the best restaurant meals in my life) — but based on the traffic the last time we were there, bike transport seems highly unlikely!

So what did I miss?

July 22nd, 2018

FDA Approves First PI-Based Single-Tablet Treatment for HIV — How Will It Be Used?

You too can learn to play the Symtuza.

The latest HIV drug approval from the FDA came this past week with the release of a single-tablet treatment containing the following drugs:

  1. Darunavir (DRV) 800 mg
  2. Cobicistat (c) 150 mg
  3. Emtricitabine (FTC) 200 mg
  4. Tenofovir alafenamide (TAF) 10 mg

Often abbreviated “DCF-TAF,” this is the first full treatment regimen in a single pill with a protease inhibitor. The approval is based on two large randomized clinical trials.

The AMBER study compared this DCF-TAF single tablet to a control arm of DRV/c plus TDF/FTC in 725 treatment-naive individuals. Virologic outcomes were similar, with renal and bone endpoints favoring DCF-TAF. There was no emergent PI resistance; one patient developed M184V in the DCF-TAF arm.

The EMERALD study enrolled 1,141 patients already virologically suppressed on a boosted PI plus TDF/FTC based regimen. (This is the largest HIV switch study ever done, for the record.) Prior virologic failure was permitted. Participants were then randomized 2:1 to receive DCF-TAF or to stay on their current regimen. Both approaches maintained virologic suppression, with no discontinuations for virologic failure. There was no emergent HIV drug resistance, and again renal and bone outcomes favored the DCF-TAF arm.

These data persuasively argue that this convenient coformulation is every bit as good as the separate tablets. There are many people still receiving darunavir-based regimens — it’s our best tolerated protease inhibitor — and most patients prefer the simplicity of having one pill, one prescription, and one co-pay.

However, the DCF-TAF tablet faces several challenges that may limit widespread adoption:

  • Many HIV treatment guidelines favor integrase inhibitor (INSTI)-based therapy over boosted PIs. These guidelines can cite several studies where INSTIs were better tolerated and/or more effective than boosted PIs. The FLAMINGO study, for example, demonstrated the superiority of dolutegravir over darunavir/ritonavir.
  • The low risk of resistance with boosted PIs is also seen with the second-generation INSTIs dolutegravir and bictegravir. This high resistance barrier in the boosted PI drug class was once a distinguishing characteristic, but no longer.
  • Pharmacokinetic boosters should be avoided in HIV treatment whenever possible. The drug interactions with ritonavir and cobicistat are extensive and frequently clinically relevant. Here’s a nicely done series done by my colleagues reviewing local data on the important interaction of ritonavir with injectable corticosteroids.
  • Several observational studies have linked treatment with HIV protease inhibitors to increased cardiovascular risk. Atazanavir appears to be the lone exception, possibly mediated by its signature side effect, hyperbilirubinemia.
  • The tablet will be expensive. The price is reportedly $41,000/year. If confirmed, this will be the costliest of the available single-tablet treatment options. With more generic antivirals available yearly, the price of HIV therapy is drawing greater scrutiny.
  • Are we moving to a “less is more” approach to HIV therapy? There is already a two-drug option approved for maintenance of virologic suppression (dolutegravir plus rilpivirine), and the release of data from the GEMINI studies of dolutegravir plus generic lamivudine is imminent. Such approaches make the four drugs included in the DCF-TAF tablet seem like too much of a good thing.

These concerns notwithstanding, as noted above there are many patients currently on darunavir-based treatments. Not everyone can tolerate INSTIs (CNS side effects are probably the most common reason for cessation), and many treatment-experienced patients already have resistance to NNRTIs. For these individuals, I suspect this new single-pill option will prove popular — provided the price and payer issues are settled.

Now, as for the brand name — “SYMTUZA” — to me it brings to mind the name of a Nepali musical instrument.

A highlight of their visit to a remote village was a brilliant trio performed on the Babucha, the Dakkari, and the Symtuza.

How about you?


July 15th, 2018

On-Service Digest, July 2018 — with Special Section Just for Staph aureus

“Hey, medicine is fun!” she said, high-fiving enthusiastically with one of her co-interns.

I’m currently on-service for the inpatient ID consult team, and this is July.

At a teaching hospital. 

Here’s where some would play scary music. After all, the interns and fellows have just started! YIKES!

But no scary music for me I love working with the July newbies.

Because whatever they lack in experience or efficiency, they more than make up for it with enthusiasm and motivation. They’re on that steep upward slope in the learning curve, and it’s fun to experience this firsthand.

Plus, there’s plenty of extra help around, and this year we hit the jackpot. In addition to an excellent first-year ID fellow, our team also has a resident with a distinguished ID pedigree and a medical student who has done ID research. If that weren’t enough, we also have a terrific ID PharmD who has his own keen residents.

Yes, we almost have enough people on rounds to field a decent softball team. We make quite the sight entering and leaving the elevator.

So what have we learned so far? Here are few items, ranging from obvious to obscure, inspired by a similar roundup last December.

Special Staph aureus section — hey, this is inpatient ID, remember?

Hey, this list of medical/surgical specialties and classic rock songs left off Infectious Diseases!

Here’s the obvious answer (with apologies to Peggy Lee and her very different song of the same name):


July 8th, 2018

Surgeon Who Was Denied Disability Insurance for Taking PrEP Tells His Story

Earlier this year, urology resident Dr. Philip Cheng appeared on the front page of the New York Times. Here was the headline:

He Took a Drug to Prevent AIDS. Then He Couldn’t Get Disability Insurance.

The piece understandably drew widespread attention, with sharp disapproval of the denial from ID specialists and public health officials. We couldn’t understand why someone adopting the recommended strategy for HIV prevention was being penalized.

“It’s like refusing to insure someone because they use seatbelts,” said UCSF’s Bob Grant in the piece. I’ve heard others cite travel immunizations and malaria prevention as analogous prevention choices. The decision by the insurance company seemed like a textbook case of discriminatory behavior.

This may all seem obvious to most of us in the ID/HIV world, but rest assured this is still not a universal view — which is why it was incredibly brave of Dr. Cheng to come forward with this story. Think of what it took for him to do this!

In this Open Forum Infectious Diseases podcast, he tells us some more about himself and the events surrounding his decision.

Well worth the listen!

July 1st, 2018

Why Do Our Patients Think They Have Spider Bites?

We are currently in peak tick season here in the Northeastern United States.

It might be hard for clinicians elsewhere to understand just how profoundly this changes our assessment of fevers and rashes. But consider this — ordering the trio of Lyme antibody, Anaplasma PCR, and Babesia PCR is as much a part of the routine diagnostic evaluation of the febrile adult in the summertime as ordering an influenza swab in the winter.

So it was with some amusement that I received the following email from a patient recently who had just been hiking in New Hampshire (some details changed as always for confidentiality reasons):

Hi Dr. Sax,
Just got back from a 2-night camping trip, and think I might have gotten a spider bite [emphasis mine] behind my left knee. There’s a dark area in the center, and a red rash spreading around it — no bull’s eye.
Anything I should do?

He included in this email a photo of the rash, which was pretty classic for erythema migrans, the tell-tale rash of Lyme Disease.

In fact, everything about his story was consistent with Lyme, including the time of year, the recreational activity (remember, hike in the center of the trail, folks!), the location of the rash (popliteal fossa is a favorite site for tick bites), and even it’s appearance — many erythema migrans rashes lack central clearing. It’s a common misconception that all Lyme rashes must be have a “bull’s eye.”

But for today, let me just focus on one piece of Gerry’s clinical history that defies explanation:

I think I might have gotten a spider bite.

I’ve never understood this mass psychosis. We first noted it when community-acquired MRSA spiked in the early 2000s. A shockingly high proportion of people seeking attention for their boils, furuncles, and skin abscesses mistakenly attributed them to spider bites.

It got so bad that the CDC issued special graphics, suitable for framing, two of which grace this post.

“When in doubt — check it out.” Clever. While these graphics may lack some of the artful touches of wartime posters warning about sexually transmitted infections, they nonetheless have a blunt and direct appeal.

In reality, spider bites are quite rare:

Spiders tend to avoid people, and have no reason to bite humans because they aren’t bloodsuckers and don’t feed on humans … In North America, there are only two groups of spiders that are medically important: the widow group (which includes black widows) and the recluse group (brown recluses).

Entomologists say that spiders as a rule are fearful of humans — makes sense, we’re much bigger than they are! They only bite when surprised, or trapped.

Which leaves us with this mystery — why do our patients so often think they have a spider bite? It’s a mystery to me.

But perhaps you, smart readers of this ID blog, might have an idea?

June 24th, 2018

A Migrating Facial Worm, and Time to Vote for Your Favorite Cartoon Caption

National Library of Medicine

Over on the New England Journal of Medicine, there’s a picture on the “Images in Clinical Medicine” series that’s getting quite a bit of attention.

And it’s no wonder. This 32-year-old woman in Russia went to her ophthalmologist with a series of selfies she took over a 2-week period. The pictures demonstrated nodules (bumps) that moved around her face — under and over her left eye, then to her lip.

It turned out to be the parasite Dirofilaria repens — of course, isn’t it always? — which is a zoonotic filarial nematode.

In plain English, it was a worm. A worm that usually infects dogs. So a dog worm was crawling around under the skin on her face. Which she got from a mosquito bite.

If you’re looking for yet another motivation to break out the DEET or picaridin this summer, look no further!

And behold, the power of the yucky ID case report. Big news indeed! Perhaps citations in Cosmopolitan and BuzzFeed will boost NEJM’s impact factor.

In other big news, our last Caption Contest drew a flurry of responses, both on the site and on Twitter. Not only that, the quality of the responses was exceptionally high, rating 9.32 (a record) on the validated Funniness Scale for an ID Blog.

Which makes me conclude that either the cartoon was exceptionally humorous (thank you, Anne!), or you are becoming pros at submitting captions — likely both. Well done!

As usual, our high-speed computer utilized the patented NEJM Journal Watch algorithm to select the top captions. Most groan-worthy puns (e.g., “I hear you’re having brelly-pain”, “That mole has really sprung” ) were automatically excluded based on Rule 17.42 — but I overturned this rule using executive action for a particularly good pun that made us giggle.

And note, we’ve added one just for ID and Microbiology Geeks — see if you can guess which one.

Now it’s your turn to pick the favorite. Have at it!

What is your favorite caption for this cartoon?

View Results

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June 17th, 2018

Remembering Robert H. (Bob) Rubin, Father of Transplant Infectious Diseases

During my ID fellowship, Robert (Bob) Rubin was my very first attending. It was the transplant service in July, and Bob and I would round with the surgeons each morning.

Early each morning. That was part of it. We needed to be there with them, before they disappeared to the OR. If we weren’t there, he explained, we might as well be invisible — they wouldn’t trust us.

This was one of Bob’s many strengths as an ID doctor, his ability to connect with our surgical colleagues. So many of us timidly leave our consult notes in the patient chart, hoping the surgical team will listen to our recommendations.

No such passivity from Bob. He spoke right to them.

It didn’t hurt that he had extraordinary clinical instincts, and was one of the most naturally intuitive clinicians I’ve ever worked with. His assessments were lightning quick, an especially notable trait in a specialty often prone to (endless) rumination and equivocation.

And, like a good surgeon, Bob was direct about everything. He knew what he knew — and told you — and knew what he didn’t know, and acknowledged this too. No hedging.

He was also by nature an active doer rather than a passive observer. In clinical care, he frequently used war and sports metaphors. No surprise — surgeons really like an ID doctor like this!

Bob is best known for his contributions in transplant infectious diseases, a field he practically created. Many of the concepts we now take for granted as accepted standard of care either originated with him or were greatly amplified by his skillful and prolific teaching.

Here are a few of these key principles (with thanks to Jay Fishman and Francisco Marty for contributing):

  • The predictable timeline after transplant for the occurrence of certain opportunistic infections.
  • The “net state of immunosuppression”, which is the sum of pharmacologic, nutritional, and anatomic factors contributing to infectious risk.
  • The compromised host as the “sentinel chicken” (a.k.a. “canary in the coal mine”) for environmental hazards.
  • The “therapeutic prescription” — he wrote: “The close linkage of infection with the nature and intensity of the immunosuppressive program has led to the concept of the therapeutic prescription. This has two components: an immunosuppressive one to prevent or treat rejection and GVHD, and an antimicrobial one to make it safe. Implicit in this statement is the recognition that changes in the immunosuppressive strategy must trigger changes in the antimicrobial program.”
  • A refusal to define a specific length of antimicrobial therapy at the outset of treatment — treat “long enough”, he would say.
  • The immunomodulating effects of certain opportunistic infections, in particular cytomegalovirus.
  • The use of “preemptive” treatments in patients at high risk for developing infectious complications — here’s his classic review of the concept.
  • Corticosteroids are like credit cards — patients (and doctors) get immediate satisfaction, but the bill comes at the end of the month. He often called them “feel goods”.

During fellowship, I remember presenting him a case one day of a man who’d had a renal transplant several years before, and was doing great — on low dose cyclosporine and prednisone, with normal renal function. He’d been struggling for the past week or so with intermittent headaches, and his primary care doctor was concerned — could this be something infectious?

My differential diagnosis was absurdly broad, including practically every known opportunistic infection that can cause headaches — listeria, cryptococcus, nocardia, aspergillus, mucor, toxoplasmosis. Cripes, I might have even mentioned acathamoeba.

Bob sat and politely listened, then kindly said — “Very good — but I’ll bet you it’s none of these things. He just doesn’t fit the pattern.”

His point — this patient was too healthy for these infections. The kind of transplant patient who usually gets these infections has been treated for repeated bouts of rejection, or experienced CMV reactivation, or has been heavily exposed to some pathogen, or is nutritionally compromised, or worst of all, all of the above — these are the “awful-awfuls”.

“If you want to send a serum cryptococcal antigen, go ahead,” he said. “But it will be negative.”

I sent it, and of course Bob was right — test negative. Turns out the patient had stopped drinking coffee because of heartburn, and was suffering from caffeine withdrawal. No acanthamoeba.

Bob died earlier this month after a lengthy illness. We will all miss him.

June 7th, 2018

What’s Your Favorite Off-Patent Antibiotic Brand Name?

National Library of Medicine

Each time the FDA approves a new drug, they also approve a new brand name.

The FDA and other regulators want something safe. They critically want to avoid names that sound or look similar to existing drugs, which could trigger medication errors. And names that imply an ingredient or an action not supported by clinical data are also off-limits.

But what if you’re a pharmaceutical company? You probably want something snappy and memorable, something that becomes practically synonymous with treatment of the condition. In this review of the drug brand-naming process, Prozac (for fluoxetine) meets all these criteria perfectly.

Marketing bliss achieved!

To counteract this commercial force, I commonly correct ID fellows, residents, and students when they use brand instead of generic names of antimicrobials.

Some would call this pointless. Others, pedantic.

Said no one, ever: Thank you so much, Dr. Sax, for correcting me when I said Z—n instead of piperacillin-tazobactam — or “pip-tazo”, as you seem to be so fond of saying.

In compensation for these years of haranguing, I hereby present for your listening pleasure a podcast on antimicrobial brand names. Joining me is the always lively and scintillating Dr. Raphael (Raphy) Landovitz, an Associate Professor of Medicine at UCLA and a longtime friend and ID colleague.

In order to avoid infringing on complicated patent law, we stick with off-patent drugs. And since people get their podcasts from all sorts of places, here are several options:

If you have your own favorite brand names, that’s what the comments section is for — but remember, off-patent only!

HIV Information: Author Paul Sax, M.D.

Paul E. Sax, MD

Contributing Editor

NEJM Journal Watch
Infectious Diseases

Biography | Disclosures | Summaries

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