HIV and ID Observations

An ongoing dialogue on HIV/AIDS, infectious diseases,
all matters medical, and some not so medical.

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August 18th, 2019

Choosing the Top Research Papers in HIV Medicine — and Recalling the Joy of Working with a Great ID Fellow

Way back in 2008 — the year I started writing here — I drafted an exceedingly long post listing the top published papers in HIV medicine.

Oh how I tortured myself over that thing.

How to define “Top”? Most cited? Most clinically important? Most rigorously scientific? Best written?

After a while, I just abandoned the monstrosity. It still sits electronically somewhere in the NEJM Journal Watch servers, forlornly awaiting a revision.

Now, courtesy of my friend and colleague Dr. Raphael (Raphy) Landovitz from UCLA, the concept lives again. He joined me for the Open Forum Infectious Diseases (that’s “O-F-I-D”, not “Oh-fid”) podcast, where we each choose our top 5 research papers in HIV medicine — plus our least favorite.

Give it a listen, or read the transcript. We’re also on iTunes, where we’d appreciate a rating if you like what you hear.

Before leaving you, just a few words about Raphy and how great he was as an ID fellow. Since we’re ranking things, he’s easily among the top ID fellows I’ve ever worked with in my gazillion years of being an ID attending. Energetic, smart, compassionate, thorough — ticked all the boxes. He also was hysterically funny.

(Brief aside — working with great fellows is a true joy. On service or in clinic with them, you totally trust their clinical instincts, and end up finishing each other’s sentences while discussing a case. A wonderful synergy in academic medicine.)

After finishing his fellowship plus a few years on the faculty here, Raphy traded our cold Boston winters for the warmth (but geologic instability!) of Los Angeles. Under the the skillful mentorship of Dr. Judy Currier, he’s had a sensational research trajectory, focusing on HIV prevention. There is not a person on the planet who knows more about PrEP. And, just this month, Raphy was deservedly promoted to full Professor of Medicine at UCLA.

Hoping you’ll permit those of us involved in some way with his training to beam a little!

Categories: Health Care, HIV, Infectious Diseases, Medical Education

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August 11th, 2019

The United States Needs Stricter Gun Control Now — and Yes, This Is an ID Issue

In general, I’ve tried to keep this site a pretty happy place.

It’s not been difficult. The ID and HIV community includes many smart, like-minded individuals involved in all sorts of interesting and challenging work, both domestically and abroad. As one of our ID fellows recalled, after he did a rotation in our ID clinic during his medical residency, “I realized I’d found my people.”

Today, however, I’m going to write about something on the sadder side, an issue tearing up our country.

We need stricter gun control in the United States. And we need it NOW.

Yes, this is a departure from prior controversies here, such as should doctors wear white coats, estimating the infectious risk of food tongs, or whether the correct abbreviation for P. jirovecii pneumonia is now PJP instead of PCP. 

I’m venturing into this more contentious* issue because it’s just too painful to ignore.

(*But to my dear readers of the ID persuasion, there’s an excellent chance you’re in complete agreement. And how do I know? Easy.)

How many of you thought, Oh no not again, when you heard the news of last week’s shooting in El Paso? And then less than 24 hours later, Oh no not again, with the news from Dayton?

And we could go on and on listing these mass shootings — sadly, we even have a Wikipedia page cataloguing them for us. It’s getting so bad that voices outside of the usual crowd feel compelled to weigh in — here’s sportswriter Joe Posnanski taking a break from his usual (brilliant) baseball coverage to write a poem describing his heartbreak.

It’s very moving. But a sportswriter writing a poem? Must be time to do something.

And lest some think this isn’t a problem related to Infectious Diseases, that I should “stay in my lane” — how wrong to think that. It’s a problem for all of us in healthcare, and, for several reasons, especially for us ID-specialists.

Crystal Zheng and David Mushatt, two ID doctors from New Orleans, astutely make the case:

During the initial hospitalization, gunshot wounds can become infected, causing skin and soft tissue infections, as well as intra-abdominal, thoracic, and brain abscesses ….Long after the initial event, gunshot survivors with spinal cord injury face a lifetime of disability, marked by recurrent infections due to autonomic dysfunction, decreased airway clearance, sensory loss, and paraplegia. These patients are at increased risk for urinary tract infections, pneumonias, infected sacral ulcers, and chronic osteomyelitis. Infection is the leading cause of death in this population. 

(Emphasis mine.)

Most of the cases we see, of course, aren’t from mass shootings. Events like El Paso and Dayton (and Gilroy and Newtown and Orlando and Parkland and Charlotte and Pittsburgh and …) get the big news, but there are way more injuries and deaths from individual shotgun wounds happening every day and night somewhere in our country.

For the victim, it doesn’t matter if the injury is from a mass shooting, an unfortunate urban skirmish, a heated domestic squabble, or the result of a deranged individual who has ready access to a gun. Their lives are irrevocably changed if they survive, often with infectious complications.

Yes, if they survive. If they don’t, those left behind suffer unbearable sadness and trauma at the loss — family, friends, colleagues. We have personal recent experience at our hospital when, in 2015, one of our rising stars in cardiac surgery was shot during an outpatient clinic session.

Oh no not again.

But look — it doesn’t have to be this way.

After last weekend’s events, I tweeted about the New Orleans perspective piece cited above, and received this response:

That’s right — 35 years of clinical ID practice, no gunshot wounds. Other countries have angry people. Other countries have urban violence. Other countries have terrorists. But only in the United States can these lead to such efficient killing.

And it’s the easy access to guns that makes our country an outlier in gun violence. It’s that simple:

I hope you’ll read the linked article, which debunks several popular alternative theories about why we have more gun violence (specifically mass shootings) than any other country. But if you don’t have the time:

Americans make up about 4.4 percent of the global population but own 42 percent of the world’s guns. From 1966 to 2012, 31 percent of the gunmen in mass shootings worldwide were American.

New Yorker writer Adam Gopnik has written frequently on this topic, perhaps because he lived in France, a place with far more sensible gun control. After the Orlando mass shooting in 2016, he wrote a piece called “One Person, One Gun” highlighting the horrible power we Americans grant our citizens — criminals, terrorists, people with mental illness, perpetrators of domestic violence — by giving them ready access to guns.

And it’s not just any handguns, but weapons designed for military use specifically to kill as many people as efficiently as possible:

So, yes, one person did do that, but it was a weapon that empowered him to do it—a weapon designed only for mass killing on the battlefield, a weapon so dangerous that soldiers keep their version locked up when not actually training with it, out of respect for its rapid-fire lethality, but a weapon that now, in Florida and elsewhere, can be placed freely and without constraints into the hands of almost anyone who wants one.

Last week, numerous medical organizations weighed in on the need for stricter gun control in this country, calling for specific actions that make so much sense it only adds to the pain that these restrictions are not already in place — among them, requiring background checks before sales, prohibiting gun ownership among those guilty of domestic violence, special regulation of high-capacity firearms, and removal of physician gag-orders on counseling about gun violence.

I can’t speak on behalf of the Infectious Diseases Society of America (our own medical society), even though I’m a member.

But I can unequivocally say that 100% of the ID clinicians I’ve spoken with agree that this is an urgent issue for all of us.

Take it away, Stephen. It may not be your funniest clip on the topic of gun control — search YouTube for “Stephen Colbert gun control”, there are plenty.

But it could be your most important.

 

 

Categories: Health Care, Infectious Diseases, Policy
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July 28th, 2019

Really Rapid Review — IAS 2019 Mexico City

Photo by Justine Camacho on Unsplash.

As I noted last week — and you did read last week’s post, didn’t you? — the International AIDS conference first took place in Mexico City in 2008. Last week we returned to this sprawling, vibrant city for the 2019 meeting.

It was an excellent, well-run conference — with one small complaint.

But more on that later… On to the content, a Really Rapid Review® of the highlights.

One big plus to this year’s conference — the number of research posters was smaller than usual, increasing the quality of accepted studies.

Also, being in Mexico City in the summer remains a joy, with cool weather (remember the altitude!), friendly people, extraordinary sites and cuisine, and relatively reasonable prices.

My only complaint? No, not the traffic — that’s terrible in every big city.

It was the conference Wi-Fi, which tortured every attendee in a particularly excruciating way. Your computer and/or phone would indicate everything A-OK, no problem, then give access to the internet in brief spurts, lasting at most seconds — followed by prolonged periods of unresponsiveness. Completely impossible to do anything.

Yes, I’ll get over it.

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July 21st, 2019

AIDS Conference Returns to Mexico City, Where We Saw an Underrated, Great Advance in HIV Therapy

If you’ve been an ID or HIV specialist for only a decade or so, the following statement might seem unfathomable to you:

Until 2008, there were lots of people with HIV whose medication adherence was perfect — but they still had virologic failure.

How could that be? The simple answer is that their virus had too much resistance to the then-available drugs.

But it’s a bit more complex than that. Several factors converged, summarized in this PowerPoint slide:

(I once upon a time thought this slide originated with Steve Deeks — but now he denies creating it, so I’ll take “credit”. Hey, good slides are like recipes, incrementally adapted until they become your own. If the originator wants to come forward, I’m happy to add your name to the slide.)

It’s those people in the blue box that have the most extreme multi-class HIV drug resistance. Treated in the early-1990s with single or dual nucleoside reverse transcriptase inhibitors (NRTIs), they already had NRTI resistance when the protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) because available in the mid-1990s.

Addition of a single active drug from these classes, often of marginal potency (nevirapine, delavirdine), or suboptimal pharmacokinetics (saquinavir, nelfinavir), or toxicity (ritonavir) acted as “sequential monotherapy”.

What we know now is that if they didn’t also add lamivudine as a new drug (which was still very active against most NRTI-resistant virus at the time), they were likely to experience treatment failure, with resistance to yet another drug class.

It didn’t help that we didn’t fully understand within-class resistance — for example, it was believed that the resistance profiles of zidovudine and stavudine were sufficiently different to transition a patient from one of these drugs to the other. Ditto certain nevirapine mutations and efavirenz. Not true!

The fact that our treatments failed in some of our most devoted and adherent patients resonated strongly with us HIV specialists. It was heartbreaking. Some had been hopeful volunteers in early clinical trials, which exposed them to inadequately dosed single-drugs that then led to a loss of this drug class. In hindsight, how ironic — and how tragic.

Others had to go through desperate (but ultimately failed) attempts to achieve viral suppression, including:

The silver lining to this resistance was that the virus became less fit; the viral load rebounded, but there was a substantial delay before the CD4 cell count declined. Patients remained remarkably stable clinically even with viremia and resistance.

This disconnect between viral load rebound and CD4 decline allowed many to survive until the miracle year of 2008, when finally we had a potent new drug in a new drug class — raltegravir, the first integrase inhibitor, approved in 2007 — plus drugs from existing classes with activity against most resistant viruses, specifically darunavir (PI, approved in 2006) and etravirine (NNRTI, approved in 2008). (Maraviroc played a less important role, since most of these patients already had non-R5 virus.)

Why bring this up now? On the eve of the 2019 International AIDS Conference, which takes place this week in Mexico City, I think back to when the conference was here last — that magic year of 2008.

It was during that 2008 Mexico City meeting that we first saw data from the TRIO study (later published here, lead by Yazdan Yazdanpanah), which enrolled participants with resistance to NRTIs, NNRTIs, and PIs, and gave them all three of these new drugs — raltegravir, darunavir, and etravirine.

The results were staggeringly good — 91% had viral suppression at week 24, a rate quite comparable to responses in treatment-naive patients with no resistance. It was actually a bit better, reflecting the high level of adherence for these motivated participants. In HIV clinics around the world, this “TRIO” regimen became the default standard for treating multidrug-resistant HIV — and it worked just as well in clinical practice as it did in the clinical trial.

At last, we could effectively treat these brave people who had weathered years of viral failure, immunosuppression, and the toxicities of early antiretroviral therapy. Many experienced the joys of hearing they had an undetectable viral load for the very first time. Treatment failure with multi-class resistance became increasingly rare — so much so that a popular HIV drug resistance test stopped selling its product, the laboratory equivalent of closing an inpatient hospice for people with AIDS.

I’m happy to report that this wasn’t a brief honeymoon phase — responses were durable, and most people with multidrug-resistant HIV have had viral suppression since 2008. The reality is that in many parts of the world, the patient with “no treatment options” due to resistance has become an exceedingly rare occurrence.

Even busy practices and referral centers see very few of these cases; in the past two years, most have seen zero:

This is not to say that it never happens anymore — a paper published recently in Clinical Infectious Diseases enrolled 20 such individuals, admitting them to an NIH inpatient center for directly-observed therapy. Of note, in this group (which included several with perinatal HIV), nonadherence turned out to be the primary reason for failure in 9 of the 20.

So here’s to 2008, a year when our knottiest HIV-resistance problems became solvable — hooray! It was a tremendous advance, one underrated in my opinion when people retell the history of antiretroviral therapy.

And what we will learn this year in Mexico City? That will be next week’s post!

Speaking of drug resistance, here’s another take:

Categories: Health Care, HIV, Infectious Diseases, Research
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July 14th, 2019

The House of God Profiled Physician Burnout Long Before We Called It That — Should Aspiring Doctors Still Read It?

Cover of my original paperback, purchased in 1980!

Many consider the novel The House of God, written by Samuel Shem (pen name for Stephen Bergman), to be a must-read for any physician or soon-to-be physician. A fictionalized account of his internship year, the book details how the accumulated stress, fatigue, and powerlessness of being a first-year doctor inexorably accumulates during that year — with sometimes hilarious, and but also disastrous, results.

The survival strategies of the interns in the book under such circumstances are not pretty. Cynicism becomes the default attitude, an us-versus-them camaraderie that considers the “them” to be not only hospital administrators and older staff physicians — but painfully, the patients, too.

Other survival tactics fall into the “instant gratification” category — the book is packed with sex, and drinking (but especially sex) — which no doubt boosted its readership, and also (warning) makes re-reading it today somewhat cringe-worthy, I imagine especially for women.

This insider look delivered by The House of God was at first widely criticized by the medical establishment. However, over time, the book has become a canonical and widely praised real-world depiction of internship — many doctors I know have read it, and it even appears in the humanistic curricula of some medical schools.

I first read the book in college, a time when I was seriously considering medical school. I found it funny, and surprising — could young doctors really be having so much sex? — but also quite sad (one of the characters takes his own life). And the grotesque depiction of the patients, especially the elderly and infirm, made me very uncomfortable, an undoubtedly intentional goal of the author to show how depersonalizing the whole experience had been.

Frankly, it filled me with dread about the prospects of becoming a doctor.

Re-reading it later, some years after my own training, I saw the extreme perspective as a necessary cry for help — these interns clearly manifested all the characteristics we now commonly refer to as physician burnout.

I could also appreciate the clinical insights embedded in the famous “Laws of the House of God”— #3 is absolutely brilliant:

3. At a cardiac arrest, the first procedure is to take your own pulse.

So my re-read found nuggets that included a human side to doctoring — The Fat Man character is clearly a great clinician — albeit these are few and far between. It’s no wonder that the online reader reviews of this book are so disparate, with plenty of angry one-star reviews mixed in with the general praise.

So why is it in the news now? And why bring it up here?

JAMA this week published a thoughtful perspective on The House of God, plus a piece by Bergman himself. It’s not just to mark the 40th anniversary of its publication; Bergman plans to release a sequel in November. Entitled Man’s 4th Best Hospital, the book will attack the current focus of healthcare on money, and screens, in particular electronic medical records, targets deserving of satire.

From a “pre-review” by WBUR’s Carey Goldberg:

But more than 40 years on, author Samuel Shem trains the satirical sights of his sequel on two particular targets: screens and money. And he connects them, pointing out that the electronic medical record systems that drive many doctors (and patients) crazy are really fundamentally billing systems pretending to be care systems.

With one of his ultra-simple syllogisms, the Fat Man sums it up:

MONEY KILLS CARE
SCREENS MAKE MONEY
SCREENS KILL CARE

Sounds like it will be another cry for help, this time to get us back to connecting with our patients — to pull us away from our electronic billing (I mean medical) records, and to care for them. I look forward to reading it!

As for why here, on an ID blog, regular readers might have gathered over the years that I have an interest in baseball.

(Hey, understatement sometimes is amusing.)

The House of God reminds me in many ways of another book from that era, the baseball classic Ball Four, another insider look at an extreme work environment — this time playing professional baseball. (And also, for the record, Kitchen Confidential. But that’s a different post.)

And last week, as JAMA released its pieces on The House of God, we baseball fans learned that the author of Ball Four, Jim Bouton, had died.

Just like The House of God, it also appeared in the 1970s, and was similarly widely criticized on release by the establishment — this time, the baseball establishment, who preferred a more white-washed, athlete-as-hero illusion of the players. But despite their protestations, the book was a huge critical success, and is now celebrated as a heartfelt and accurate account of what it’s like to live through the grind of a not-so-successful baseball season.

Also like The House of God, the book is very funny, and the players resort to plenty of sex and drinking (but especially drinking this time) — ways to overcome the stress of incessant performance demands, contract disputes, and relentless travel in a sport where management can dispassionately trade you to another team or drop you to the minor leagues for any decline in productivity.

But Ball Four differs from The House of God in two critical ways. First, it’s an autobiographical account, not fiction — these are real people, and it’s Bouton’s voice we hear telling the story.

Second, and more importantly, the joys of playing the game come through strongly. The many problems Bouton has on that 1969 Seattle Pilots team notwithstanding, he clearly loves baseball and deeply respects the hard-work and talent it takes to succeed at this professional level.

A much-quoted line from Ball Four captures this love perfectly:

A ballplayer spends a good piece of his life gripping a baseball, and in the end it turns out that it was the other way around all the time.

There’s nothing like this in The House of God — no joy from patient care, or their gratitude, or how rewarding it can be to master medical information over the course of residency, and then pay it back by teaching medical students and interns. Sure, there’s camaraderie in the book, but much of it is soured by the brutal experiences they are living through.

One of my colleagues has suggested that people wait until after they complete residency before reading the book.

I think he’s right.

What do you think?

Have you read The House of God?

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July 7th, 2019

In Praise of Experienced ID Fellows — and a Dozen On-Service ID Learning Units

A few weeks ago, I cautioned ID fellows about underestimating their hospital’s interns and residents.

My message — you were like them not so long ago; they didn’t suddenly all lose their brainpower when you graduated. This ungenerous opinion of house staff may be especially held by experienced fellows, as the accumulating workload of the year can lead to impatience.

OK, grouchiness.

The post might have felt a bit tough on current fellows, but that was not my intention. As I noted at the start (citing my own experience), it’s nearly a universal illusion, one we all have to get through.

So here’s the flip side of working with those experienced ID fellows — for us attendings, it’s wonderful.

I frequently attend on the inpatient ID service during the transition period between fellowship years, and once again it’s been an absolute joy to witness the expertise and confidence of these seasoned pros as they finish their fellowship year.

Their clinical instincts. Their remarkable growth in fund of knowledge. Their ability to assess, rapidly, not just “sick” vs. “not sick” — that starts with residency — but even more importantly, “sick from an ID problem” vs. “sick from something else entirely; the ID issue is secondary.”

The skills go on. The experienced ID fellows focus their diagnostic and therapeutic suggestions in ways that would have been impossible for them just months ago. They handle serious, difficult ID problems — Staph aureus bacteremia, a new HIV diagnosis, epidural abscess — with confidence and aplomb. They communicate with patients, family members, and consulting teams accurately and clearly, without excessive jargon.

As they present cases on rounds, I await their assessments with deep interest — as more often than not they have insights about diagnosis and treatment that are spot-on.

Plus — and this is a tough one — they recognize that the late afternoon or weekend consult may be highly appropriate, and not just an annoyance, no matter how busy the day.

So thank you, ID fellows who have just finished their first year — it’s been a blast.

And here’s a list of some of what we discussed on rounds — a dozen “Learning Units” for each day on service:

And finally…

Categories: Infectious Diseases, Medical Education, Patient Care
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June 30th, 2019

Antibiotic Development Is Broken, Brothers in ID Practice, and This Year’s Winner of the ID-Related Social Media Award

“I do not like thunderstorms,” said every dog, ever.

I am currently rounding on the inpatient ID service, the new ID fellows arrive shortly, and Louie needs intensive doggy psychotherapy after yesterday’s strong thunderstorms here in Boston.

Busy times!

As a result, today’s post has no unifying theme. But what it lacks in cohesiveness it more than compensates in value, as here are three highly interesting ID-related items for your perusal.

1. Antibiotic development is broken — and how to fix it. 

This fascinating perspective in the New England Journal of Medicine focuses on the problems with our current model of antibiotic drug development. Why are for-profit companies abandoning antibiotic research? If antibiotic resistance is such a problem, why isn’t this “market opportunity” giving us new and better antibiotics?

The absolute number of infections caused by each type of resistant bacterium is relatively small. Each newly approved antibiotic thus captures an ever-shrinking share of an increasingly splintered market — a problem that will only worsen over time. Short treatment durations and a coordinated program of antibiotic stewardship also contribute to low sales.

The authors’ proposed solution is to fund nonprofit organizations to develop antibiotics. Unlike private companies, they would not be beholden to shareholders to generate rapid profits. Relatively small revenues for a large private company — tens of millions of dollars annually — would, for a nonprofit, be a substantial win, and a chance to reinvest this money into further research.

Now they just have to convince some entity — government? philanthropy? — to invest the seed money to get this started.

A big hurdle, yes, but at least it’s a path forward.

2.  Two brothers chat about being in ID practice — together.

For many academic ID fellowships, the intense first year of clinical care is followed by years of research training, with relatively little clinical work occasionally sprinkled in.

Research fellows might have a once-weekly half-day in clinic, or an occasional weekend seeing consults.

That’s the pathway Dr. Steve Threlkeld followed here in Boston when I first knew him as a brilliant ID fellow. (I was just starting my first faculty job.) However, he soon came to the realization that his true love was patient care, not research.

So he did something novel — he joined his brother Mike’s private ID practice in Memphis, Tennessee.

Steve and Mike chatted with me on this OFID podcast about private practice ID, what it has in common with academic ID and what’s different, how to be a blue-leaning clinician in a red-leaning state, and the unique opportunities and challenges of being the only sibling-owned private ID practice in the universe.

OK, someone contact me if I’m wrong about that last part.

Available also on iTunes, Overcast, and soon other podcast places.

3. This Year’s Winner of ID-Related Social Media Award.

I don’t know Dr. Philip Lee, but if there’s an Academy Award for ID content on social media, he’s the unequivocal 2019 winner — and we’re only halfway through the year.

Click on this Twitter thread for the incontrovertible proof:

And fear not! One-a-Day ID Learning Units are coming soon.

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June 23rd, 2019

Advice to Incoming Subspecialty Fellows — Don’t Underestimate or Belittle Your Interns and Residents

An Unsmart Bulb (Photo by Ashes Sitoula on Unsplash)

Around a million years ago, early during the first year of my ID fellowship, a medical intern consulted me about an elderly patient with a urinary tract infection.

Me:  Does she have a catheter?

Intern: I don’t know.

Me: Has she been admitted before with a UTI? Any cultures?

Intern:  I think so — wait, I’m not sure. Let me check her chart.

Me (testy):  Nevermind — we’ll come by and see her. (Slams down phone.)

It might have been a busy day for me. Or a late afternoon consult. For whatever reason, I was feeling pretty fried.

Over the next week, I channeled my frustration with this exchange by citing it several times as an example of the general cluelessness of the current interns and residents — house staff at the very fine hospital that kindly had accepted me to their fellowship.

But wait. That can’t be right.

Indeed, let the record show that I was emphatically wrong — the interns and residents during my fellowship were outstanding. This particular intern had a PhD in immunology and was just getting started as a doctor. No surprise that not all the details were immediately at her fingertips.

I bring this up today because right now, in many teaching hospitals, the interns have already begun, and the subspecialty fellows are waiting in the wings. Most start in the next week or so.

It’s therefore a perfect time to take on this commonly held (and sometimes, alas, openly voiced) opinion by some subspecialty fellows as they grow into their new roles:

These interns and residents are weak!

There are numerous triggers to this ungenerous thought. Most involve consults deemed “inappropriate” by the subspecialty fellow, for a variety of reasons:

  1. Consult called without having complete information. (My example.)
  2. Consult called without asking the right question. (How can they always know the right question if they need help on a case?)
  3. Consult called “too early” in the admission, without the house staff doing the full initial work-up.
  4. Consult called “too late” in the admission, with the house staff mismanaging the case before calling the consult. (Look how the residents can’t win here, with both #3 and #4 suggesting some magical precise correct time for calling a consult.)
  5. Consult called too late in the day.
  6. Consult called by the medical student, which is deemed insulting to the newly minted fellow. (Oh come on.)
  7. Consult called for something the fellow would have handled without a consult when they were residents. 

I bolded this last one since it’s probably the most common example. (Junior faculty sometimes succumb to this one as well. It’s an early form of, “In my day …”) What weakness!

So let me emphasize, again, by noting, emphatically, that this perception is a total illusion.

There is zero evidence that interns and residents are weaker, less thoughtful about patient care, and less thorough than we were during residency, whenever and wherever that may have been.

How do I know? Because there’s a control group — those who do their fellowships in the same hospital as their residency. These fellows sometimes cite weakness in residents who were, until very recently, their colleagues. And folks, it’s literally impossible that suddenly and unexpectedly, the entire house staff regressed, losing all their clinical skills when said fellow graduated.

So what’s behind this negative line of thought? And what can we do to correct it?

To answer these questions, a few months ago I posted the following:

Encouragingly, many responded that they feel that today’s house staff are wonderful.

But some acknowledged that the phenomenon exists, and offered various thoughts about its origins. I like this response, from ID colleague Dr. Andrej Spec (who may be better known on ID Twitter as @FungalDoc):

Nostalgia. That, and as we get better, it becomes easier to see the mistakes that we were oblivious to previously. The solution is to keep remembering the times we made mistakes. So that we put ourselves in perspective.

Or, from a rheumatologist (@Doctorkuch):

Thinking that everything you know now, you knew then (false!). #constantlylearning

These comments get right to the heart of the problem. We spend the years of residency honing our craft, becoming better at what we do through clinical experience, teaching conferences, and reading. By the time we are in our last year of residency, there’s a wonderful sense of mastery — that’s the good part.

The bad part is that we may unfairly expect similar mastery from our junior trainees.

So the next time we feel like criticizing an intern or resident for not having all the information, or not consulting at the right time, or calling a consult on a case we think we would have handled ourselves without a consult — remember what it was like to start your training.

And remember, this doctoring thing is hard — a lifelong exercise in learning, and trying to get better.

It may not be quite as difficult as getting this “smart” light bulb to work, but it’s close.

So how many ID docs does it take to change a light bulb?

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June 16th, 2019

On Father’s Day, a Tribute to a Father Who Isn’t Allowed to Celebrate Father’s Day

Part 1. My Father and How I Became a Doctor

I became a doctor with encouragement from my father.

Wait, let me rephrase that to capture what happened more accurately.

I became a doctor with a fair amount of pressure from my father.

Fresh off an adventure abroad, in my early 20s, I had all kinds of pretentious ambitions for my future. 

Screenwriter. Comedy writer for a hit television series. Stand-up comedian. Fiction writer, periodically tossing off stories to The New Yorker while writing The Great American Novel. 

Mind you, I had no idea how to make these aspirations actually happen. My writing output to that point included a few comedy pieces for the Harvard Lampoon (most of them in hindsight rather unfunny), and a piece in the Boston Phoenix (may it R.I.P.) describing my experience in a yogurt taste-test. 

“Go to medical school,” said my father. “You can do anything once you have your degree.”

Absent an alternative plan — and trust me, there was no alternative plan — who was I to argue?

Spoiler alert — he was right.

Part 2. My Father, and How He Became a Doctor

My father comes from a family of doctors — and that’s understating it. His father, his uncle, his cousin, his brother — all doctors. His mother was a nurse, but probably would have been a doctor if Jewish women could go to medical school in Moscow in the early 20th century.

(His sister, my aunt, also married a doctor. In hindsight, what choice did she have?)

Medical pedigree notwithstanding, my father’s path to his MD was not easy. Skipped ahead twice in grade school because of his precocious reading skills, he entered college at age 15. 

Unsurprisingly, he wasn’t ready for college life, and struggled socially and academically. Lonely, homesick, and with mediocre grades, he dreaded his own father’s visit during freshman year. Apparently, my grandfather didn’t take well to academic underperformance in his children.

But that visit never came. On the way to see my father in college, my grandparents were in a bad car accident. Both were severely injured, my grandfather didn’t survive.

It’s very hard to get inside the head of anyone, but imagine yourself at a university at age 15. You’re way too young, and already not doing well. And then this happens — your father dies, your mother injured. There are a million ways this story could go, most of them not good.

But my father’s response, amazingly, was to grow up — and to grow up fast. He doubled-down on his studies; he made friends. He applied to medical school — close to home so he could support his mother — and was accepted.

After residencies in both internal medicine and psychiatry, he became a practicing psychiatrist, and an esteemed teacher, jobs he truly loves.

I’ve always wondered if his college experience drove his choice of specialty, his desire to make something positive of the lessons learned enduring that trauma.

But that’s just the psychiatrist’s son speaking.

Part 3. My Father

Having married the unsentimental, smartest person in the world, my father can’t celebrate Father’s Day.

But I can do it for him, by listing here his best character traits:

Enthusiasm. The joke in my family is that my father will eat or drink something objectively mundane — a Ritz cracker, a glass of water — and stop conversation by saying, “This is the best water.” But the great thing about this enthusiasm is that it applies up and down the spectrum of experience, from those Ritz crackers and glasses of water to Chateau Latour, German expressionist art, 19th Century American literature, and tropical fish. (That last one ended badly, at least for the fish.) And as far as I’m concerned, we can’t have too many enthusiasts in the world — these are the people who brighten up the room when they enter.

A genuine interest in others. People invited to a dinner or other social event usually stick to the people they know, the familiar faces — it’s the easy route. But my father has always viewed the newcomers or strangers at these gatherings as fascinating sources of new life stories. He is deeply interested in others, and as a result is great company. And when you think about it for two seconds, it’s the perfect character trait for a psychiatrist. No wonder he loves his work, and is so good at it.

No detail is too small. There are “big picture” people out there who can’t be bothered with the small details. Then there are those who, on finding a topic they find interesting, can’t learn enough. My father is clearly in the latter camp, a voracious reader who delves deeply into a subject until he could practically write a PhD dissertation on it. You know that tower of books everyone has by their bedside? My father must be one of the few people on the planet actually to have read his entire stack.

Supportive of the people he loves. As I wrote last month, my mother went to graduate school and back to work when I was 11, leaving us three kids at home. (Sob again, but I’ve gotten over it.) In that Mad Men era, not all men would have supported this move, but my father did just the opposite — he became my mother’s biggest fan, constantly telling us and others how successful my mother had become. Let the record show he’s had the same attitude to all our personal and professional decisions — and in hindsight I believe he would have been fine had I not attended medical school, provided I was trying to do something.

So Happy Father’s Day, Dad! And I agree, those Ritz Crackers are great.

(Back to our usual Infectious Diseases programming next week.)

 

 

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June 9th, 2019

Is It Safe to Alter the CCR5 Receptor? And How Will This Influence HIV Cure Studies?

The HIV cure effort suffered a potential setback this week, as researchers reported an association between having two copies of the CCR5-∆32 mutation and shorter survival.

(Quick reminder — the CCR5 receptor is required for most HIV strains to enter target cells. People homozygous for the CCR5-∆32 mutation are almost completely protected from contracting HIV.)

By evaluating over 400,000 individuals in a British registry that included genetic information including CCR5 status, the investigators compared the prevalence of CCR5-∆32 homozygosity among people between the ages of 41 and 76. Over time, the prevalence substantially declined, consistent with a 21% increase in all-cause mortality compared to those with either no ∆32 mutation, or heterozygotes.

The authors postulate that this excess mortality may be driven by the reported worse outcomes among those with ∆32 homozygosity who develop influenza or other infectious diseases. Since most influenza deaths occur in older people, this could explain why earlier studies of populations with ∆32 reported them to be healthy.

(By contrast, it might be that historical epidemic infections of childhood and young adults — smallpox, plague, dysentery among them — could have selected for ∆32 many centuries ago, with the result that approximately 10% of people of European heritage carry at least one mutation.)

As noted in the excellent editorial accompanying the new study, the findings should give researchers pause before making permanent changes to the host genome:

The most important point raised by the current publication is that considerable risk comes with generating mutations in the genome of human beings, no matter how obvious the benefit that those mutations offer.

I’d amplify this concern by noting that individuals born with two CCR5-∆32 mutations — who grow up with it — may differ from those in whom CCR5 is altered during adulthood. We simply don’t know whether people who acquire it late in life will be better or worse off than those born with the mutation.

So why is this recent study relevant to curing HIV? Considerable research has already been done on this receptor related to HIV cure:

  • Only two people — the “Berlin” and the “London” patients — appear to have been cured of HIV. Both underwent stem cell (bone marrow) transplantation using donor cells harvested from people homozygous for the CCR5-∆32 mutation. The indications for the transplants were refractory leukemia and lymphoma for the Berlin and London patients, respectively. Both are off antiretroviral therapy with no viral rebound, and no virus detected either in blood or tissues.
  • Zinc-finger nucleases successfully excised the CCR5 receptor from some cells of people with HIV. This small study (n=12) was a first step in trying to engineer something analogous to the Berlin and London patients without the risk of stem cell transplantation.
  • A scientist reported that he used CRISPR-Cas9 genome-editing to disable the CCR5 gene of two babies. The announcement was hugely controversial, as there was zero medical justification for this experiment on these children born to an HIV-negative mother. However, the cases underscore the feasibility of altering a person’s genome using the powerful tools available today.
  • There is substantial ongoing research in coreceptor modification to prevent or cure HIV. In the linked review, it states “there are multiple clinical trials underway to evaluate how efficacious this therapy can be in human patients.”

Clinicians not actively caring for people with HIV might wonder whether the risks are worth it — isn’t HIV therapy now safe and all but 100% effective?

The reality is that there’s tremendous interest in HIV cure, especially among those with HIV, risks notwithstanding.

So great is this interest that many of us have even been asked by our patients whether they can have a bone marrow transplant:

That these questions mostly come from people doing quite well on their HIV therapy signals a powerful patient-driven motivation for HIV cure — one that sadly seems more related to ongoing HIV stigma than to the medical issues of current HIV treatment.

Which is why it’s not so clear that this latest research finding should dampen the pursuit of CCR5-driven cure strategies.

Would a lifetime 21% increase in all-cause mortality be an acceptable trade-off for a person with HIV who is deeply invested in HIV cure?

And who will get to decide?

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HIV Information: Author Paul Sax, M.D.

Paul E. Sax, MD

Contributing Editor

NEJM Journal Watch
Infectious Diseases

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