Sensible Medicine

Remarks about a model clinician.

It would be foolish to argue that doctors are unaffected by how they are treated by patients. Their treatment may not affect the care they deliver and only affect how they feel at the end of the day. It is probably impossible to know.

When I type the words coronary artery disease I bet that you picture angiograms with stenotic lesions—blockages in colloquial language.

Indeed a high grade plaque from atherosclerosis in the inside of a coronary artery can limit flow to the heart muscle.

But. But. Not as much as you think. You know why? Because there is something called the coronary microcirculation. Before blood gets to the beating heart muscle it has to go through small blood vessels. So small that you can’t see them.

A study in the NEJM—on one patient—elegantly shows the ability of the microcirculation to autoregulate blood flow in the face of increasing degrees of obstruction in large coronary vessels.

We’ve all seen patients who have severe flow-limiting proximal stenoses, which create little to no angina. A likely reason is the ability of the microcirculation to dilate and improve blood flow—at least at rest or minimal exertion.

My friend Venk Murthy explains this elegant study. I learned a bunch and likely you will too.

We refer often to this figure from the paper. It would be useful to have it handy while you listen.

JMM

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VP fixed the audio

Regard for power implies disregard for those without power; part 3

David Cohen is one of the smartest docs on Twitter. I learned a bunch talking with him.

The procedure called transcatheter aortic valve implantation or TAVR is a damn miracle.

In days of old, a heart surgeon would have to saw open the chest and cut out the heavily calcified immobile aortic valve and sew in a new one. I watched a case as a young doctor and came away shocked that patients survive this surgery.

TAVR is even more stunning. Doctors place a valve up the aorta, across the diseased valve, and then place the new valve into the old valve. The verbs squishing or smooshing come to mind.

The other unbelievable thing about TAVR is that strokes are less common than you’d think. When I first heard about TAVR, I thought: how is it not limited by all that debris going into the brain?

Well, there is less debris than I would have thought. But not zero debris. In fact, there is one device on the market that forms a barrier between the aorta and the brain. We call it an embolic protection device (EPD) or cerebral embolic protection (CEP).

Early studies show that the device catches debris that would have occluded blood vessels in the brain—iow, caused stroke. The pictures almost sell the device—because, obviously, catching debris has to be beneficial.

But. But. There are always ‘but’s’ in Medicine.

The PROTECTED TAVR trial, which compared TAVR with and without an embolic protection device failed to show a statistically significant reduction in stroke. It was a good trial, but it did not close the door for the device. For two reasons: one was that the trial was underpowered. The lower bound of the 95% confidence interval allowed for a 1.7% lower rate of stroke in the treatment arm. Neurologists feel that a 1% risk reduction in stroke is clinically important. The other reason was that a secondary endpoint of “disabling” stroke was 60% lower with the device.

We needed more data. Another trial is not likely going to happen. Trials are expensive and take a long time. This is where Dr Cohen’s group comes in. They performed an observational study looking at more than 400k patients in a TAVR registry. About 13% got the device and 87% did not. This is where Sensible Medicine readers should start feeling a rash.

Why? Because you know how scary it is to try and compare outcomes in two groups of patients who were not randomized.

Cohen, however, tells me about a super-interesting way to approximate randomization in this comparison. It’s called an instrumental variable analysis. He explains this to me in clear terms during our conversation. I love methods so I was enthralled. But that isn’t all. The other thing is that his study, like the PROTECTED TAVR trial, came up with tantalizing close results. We discuss that as well.

I loved our talk. If you like evidence, methods, and great medical stories, I think you will also like this conversation. JMM

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A spirited discussion of craziness in medicine

MM is 94 years old. Her only active medical issues are hypertension and vitamin D deficiency. She takes only 20 mg of lisinopril and 1000 units of vitamin D3 each day. She has no cognitive decline and gardens every day if the Chicago weather allows. Her Friday afternoon appointment is the doctor’s last of the week.

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I’ve already written a reflection on four things patients have taught me. After MM’s visit, I realized how much more there is to write on the topic. So here is a follow up with the unoriginal claim that the most valuable things I have learned from my patients are not about the practice of medicine. Though not profound, the lessons are universal. The longer I practice, and the older my patients get, the more frequently these truths are spoken.

Aging is Painful

Anybody who gets to middle age knows that things don’t work like they used to. Around my house we say that any day that nothing hurts is remarkable. My patients are full of pithy phrases to make the point that aging is physically difficult.

“Getting old is hard, but it beats the alternative.”

“Aging is not for wimps.”

“Every time I look in the mirror, I ask myself, how the hell did that happen?”

People respond to their progressive disability in all manners. Some fight at every turn. Every visit, irrespective of age, is spent discussing aches, pains, and things that can no longer be accomplished. There are demands for me to make things better. I find it challenging to address the concerns, rather than dismissing them with “it’s just age,” while also letting people know that some suffering is “part of the human condition.”

Other people accept frighteningly steep and acute declines. My challenge at these visits is to balance, “She’s not asking me to address the problem, so who am I to pry” with “This actually seems like something I should explore, even if she is willing to accept it.”

Where there is little diversity is our ability to adjust to disability. I was taught that people rate the quality of life with a disability higher when they are living with it than when they are watching other people live with it. Thirty years of clinical experience has made this real. We should add to the saying, “There but by the grace of God go I” the addendum “but, when I end up there, I’ll be OK.” 

Aging is Sad

When I was an intern, I admitted an elderly woman with pneumonia. Her biggest problem was not the pneumococcus but her depression. Her mood made her miserable and the associated psychomotor retardation was going to make her post-hospital rehabilitation impossible. She was already taking an SSRI and seeing a therapist. I called her primary care doctor, a geriatrician. Like a true intern, I expected he would have an answer to her misery. His response was, “Yup, it is a sad time of life.”

There is a lot to be said for the golden years: retirement, family, friends, greater financial security – but as the years go on, the psychological costs mount. Besides the physical decline, there is the constant loss. I repeatedly hear, “Everyone around me is dying.” Siblings, cousins, friends. It sometimes seems like those who are most connected suffer the most – that big family that has always provided support now provides an unending procession of funerals.

People mourn their losses as well as their own mortality. You cannot ignore what is to come when your peers are dying. Those who deal with this best seem to be the people who can be honest that their grief about the loss of a friend is partly the fear and sadness that they are next.

Loss is Never Easy

I never felt like I had enough time with MM. Not that she needed time for me to attend to her medical problems. She was blessed with enviable genes and an outlook that combined cheer and steel. I just wanted time to hear more about her life and her experiences. I wanted to learn from her.

On one unpressured Friday afternoon we chatted. I did not have another patient to see, another note to write, or another meeting to run to. Her daughter would not pick her up until 6:00 PM. I told her that I still thought about her husband, also a patient of mine, who had died about a decade earlier.

She paused and then remarked. “We lived together in the same old house for more than 60 years. Every time something stops working there, I curse the damn house and I curse Charles for leaving me alone in it. He was always puttering around, fixing things. Then, of course, I think of the wonderful years we had here. I cry because I still miss him, and then I thank the house for reminding me of him.”

I can’t write anything original about loss and grief and mourning. We’ve been writing about it for as long as we’ve had written language. What strikes me, though, watching so many people experiencing loss, is that it is always hard. Losing a loved one is hard. It does not matter if your father is 50 or 90. It does not matter if your mother’s death is sudden or expected. It does not matter if you have come to terms with the complexity of your relationship with your sister or have not.

Our losses become a part of us, they shape us. The tearing, searing grief might last days, or weeks, or months, or years, but it always ends. Nobody, however, ever “recovers.” Nobody “gets over it.” Having known, having loved, and having lost makes us who we are.

A few short words about our conversation:

Two decades have passed and electrophysiologists have learned little about how to ablate atrial fibrillation. Now, and then, we simply ablate circles around the orifices of the pulmonary veins.

This works reasonably well. But we don’t—exactly—know why it works. For instance, some patients have total elimination of AF, but when they are restudied, they have reconnection of PV activity.

Observations like these suggest there is something else happening with our ablations—beyond building an electric fence around the veins.

One possibility is that we are affecting the neural input to the heart. Structures called ganglionic plexi sit next to the areas we ablate. We often see heart rate increases after AF ablation. Say, from 60 to 80 bpm. That’s because ablation has reduced parasympathetic input to the heart.

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Piotr and his team had to suspend typical AF ablation during the pandemic. Surgeons would not provide backup. This gave them the idea of a simple approach—only in the right atrium, with one catheter, and no anesthesia. It turns out that there is often a ganglionic plexus in the upper right atrium.

They found patients who had a history of vagally-mediated AF. They documented that these patients had high vagal tone. And… in these patients, simple ablation in the RA yielded a signal of benefit, a reduction of AF. Wow.

It’s a small single-center study. It’s just a signal. A first mile of a marathon. But for the curious regarding AF, it is super-interesting.

Many athletes and young people have vagally-mediated AF.

Here is the link to the paper: Cardioneuroablation of Right Anterior Ganglionated Plexus for Treatment of Vagally Mediated Paroxysmal Atrial Fibrillation

Here is Piotr. He works in Rzeszów, Poland. It’s a beautiful city to visit. I once ran a marathon there. JMM

We discuss the state of medical education, Harvard music video, causal language at JAMA and more

Video will be available to paid subscribers

Gosh was this a great conversation about her recent paper on specification curve analysis of nutritional observational studies.

Here is Dr. Zeraatkar’s bio:

Dena Zeraatkar, PhD is an Assistant Professor in the Departments of Anesthesia and Health Research Methods, Evidence, and Impact (HEI) at McMaster University. She earned her doctoral degree at McMaster University in the Health Research Methodology graduate program. Following her doctoral training, she pursued postdoctoral training at Harvard Medical School, for which she was awarded a Banting scholarship.

Her research centers on evidence synthesis and evaluation—identifying and appraising research to optimally inform healthcare and public health decisions. She often works in areas in which the evidence is complex or conflicting, examples of which include nutrition and COVID-19 therapeutics. For her research, in 2023, she was awarded a Gairdner Early Career Investigator Award.

First, it would help to read my comments yesterday on the paper. Dr. Zeraatkar is well-spoken, clear and she explains a complicated topic in simple terms. Her work is exactly the type we love at Sensible Medicine. Stay for her final comment. It made me so happy.

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The Thomas Sowell quote, “On closer scrutiny, it turns out that many of today's problems are a result of yesterday's solutions” has been ringing in my head a lot lately.

Gosh was I lucky to speak with Professor Erik Van Zwet from Leiden University in the Netherlands. He is the first author on a recent NEJM Evidence paper looking at more than 23,000 trials in the Cochrane Database. (I linked to an URL that should get by the paywall.)

There are technical aspects of this paper. We hit on some (not a lot) of them. The gist of it though is really important when we look at evidence. Erik did an excellent job of explaining P-values, trial power, and, at the end, we discuss how this work might inform the ability of trials to replicate.

This discussion also pairs well with one I had with computer scientist Ben Recht.

I hope you enjoy the conversation.

Please do consider subscribing or supporting our work as Sensible Medicine remains an ad-free user-supported place to learn about medical evidence. JMM

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Why have I been committed to medical education? Some of the reasons are admirable but not terribly novel. Others are a bit hard to admit, but just as true.

Friday Reflection 35: Why Don’t Doctors Want to See Patients?

I was asked “Why is it that doctors don’t want to see patients?” and I could not answer the question. Fourteen months later, here is my response.

Ben Recht is a professor at UC Berkeley. You know, the place that has all those parking spaces for the Nobel laureates.

He understands the innards of math. And that is exactly why he explained that doctors who use evidence don’t have to get bogged down in technicalities.

I reached out to Ben to discuss a complicated but provocative statistical paper in NEJM evidence. But we mostly talk basics.

Ben writes at his Substack arg min

As many of you know, I have long argued (unsuccessfully until now) for a placebo-controlled trial of AF ablation. One group gets the ablation; the other gets a placebo or sham procedure. This way we can sort out the placebo-resistant effect of the ablation.

Finally, here is the first report of one.

Dr. Malcolm Finlay is an electrophysiologist at St Bartholomew hospital in London UK and primary investigator of the study. They recently published their feasibility study for AF ablation vs placebo.

The American Heart Journal published the pilot study of 20 patients.

Finlay and colleagues call it the ORBITA AF trial. But it’s important to note that this was done separate from the ORBITA investigators at Imperial College. The larger study will have a different name.

Here is a copy and paste:

Twenty patients with PersAF (duration <2years) were recruited, representing 10% of the proposed larger trial as determined by a power calculation. The patients were randomized in a 1:1 ratio to receive either PVI±DCCV(PVI group) or DCCV+Placebo(DCCV group).

The primary endpoint was to evaluate the blinding of the patients.

The good news is that it mostly worked. Blinding was successful in most patients. Recurrence of AF was less in the ablation vs cardioversion arm. But the numbers were too small to say much. Same with quality of life measures, which were mostly similar until 12 months.

The authors concluded that

This feasibility study establishes the potential for conducting a blinded, placebo-controlled trial to evaluate the efficacy of PVI versus DCCV in patients with PersAF.

I hope you enjoy the conversation.

This is darn exciting for the field.

And I am delighted to publish this conversation on Sensible Medicine. (I also tried to include the un-edited transcript of the conversation.)

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These patients did the right thing leaving my care. We were wrong for each other, or I had given what I had to offer (at the time) and it was not enough. That does not lessen the feeling that I failed.

They say dying alone is sad. They also say we all die alone. There is trauma to not dying alone as well. 

If you care about AF you will love this conversation.

Soren has some interesting ideas about what AF is now vs what AF was in the past. Here are some links:The LOOP Study (which was non-significant).

Effects of Atrial Fibrillation Screening According to N-Terminal Pro-B-Type Natriuretic Peptide: A Secondary Analysis of the Randomized LOOP Study

Severity and Etiology of Incident Stroke in Patients Screened for Atrial Fibrillation vs Usual Care and the Impact of Prior Stroke: A Post Hoc Analysis of the LOOP Randomized Clinical Trial

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BTW: This is the kind of content we aim to bring you at Sensible Medicine. Thanks for your support. I have some great ideas for future conversations. Feel free to let me know your interests, too.

The study in question is a randomized clinical trial looking at the Million Hearts Model. This model paid health care organizations to assess and reduce CV risk.

Obviously, this is an important goal. Heart disease, specifically, atherosclerotic vascular disease, is a leading killer of humans. Any reduction of heart disease should have a benefit on both a person and a population.

But paying health systems to do specific things is a policy intervention. Even though a policy, like this one, makes sense, policies can have benefits and potential harms.

(An example is the hospital readmissions reduction program (HRRP), which penalized hospitals for excess readmissions. This resulted in a fewer readmissions but it also associated with an increase in death rates in patients with heart failure.)

Both Andrew and I were happy that the nudging of Million Hearts was studied

The Trial and Program

This was a big pragmatic cluster randomized trial that ran over 4 years. More than 300 organizations were randomly assigned 1:1 to have the Million Hearts model or standard care.

There were two parts of the model. First there was $10 for every patient who had their 10-year risk calculated with a risk equation. (ACC/AHA is a simple one you can do in 15 seconds with a smartphone.) Then CMS paid each organization $0, $5, or $10 PBPM for each high-risk beneficiary with an annual risk reassessment, with monthly payment amounts dependent on mean risk score change across all of the organization’s high-risk beneficiaries reassessed.

Keep in mind that the only components of the risk calculation that are modifiable are cholesterol and blood pressure. (*smoking cessation for smokers).

Foy pointed out that Million Hearts was in many ways an incentive system to nudge providers, who then may nudge patients, to take more BP and cholesterol medicine.

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The authors chose two primary outcomes: one a MACE endpoint with MI, stroke, and TIA. The second primary was the same as the first, plus CV death.

They originally planned to include only high-risk patients, but then added moderate-risk patients. This factored heavily in the results. Patients were mostly 75 year-olds, men-women split 2/3rds, 1/3rd. Outcomes were derived from claims data—which is messy when it comes to judging MIs and TIAs and specific causes of death.

The Results:

The first primary endpoint (MI, stroke, TIA) occurred at a rate of 14.8 per 1000 patient-years vs 17.0 per 1000 patient-years. The Hazard ratio came to 0.97 (90% CI - 0.93-1.0). The P-value was 0.09. (The authors had previously stipulated that the P threshold would be 0.10). The second primary, adding in CV death, was similar. A HR of 0.96 (90% CI 093-0.99) and a P = 0.02.

These are positive results. But let’s look further.

Drivers of the Results: The results were driven almost exclusively by moderate risk patients. Look at Table 3. Reductions in events rates were largest and significant statistically in the moderate-risk but not high-risk group.

That is something we have emphasized here at Sensible Medicine. Even though you would think that high-risk patients have the most to gain, they also have more competing risks and perhaps more chance for treatment harm. Like so many other studies, the sweet spot for primary prevention seems to be in the moderate-risk group.

Unintended Consequences: A second finding, noted by Andrew, was the highly significant increase in all-cause hospitalizations in the intervention group. These had the most significant p-values of the entire study.

Other Limitations:

The Million Hearts model randomization was offered to more than 500 organizations but only 342 accepted. This raises the question of generalizability. Were the 342 organizations special in some way?

Another factor is that outcomes were modeled on a sample of events—not raw counts.

The choice to use 90% confidence intervals rather than 95% confidence intervals and P thresholds of 0.1 rather than the more standard of 0.05 is a weakness. For instance, the first primary endpoint would have missed significance if this were evaluated in the usual fashion. I did not find a strong justification for this choice. Readers with statistical expertise, please weigh in.

Our Conclusions:

First, we were both happy that a policy was studied rather than just implemented because it made sense. This should serve as a model for future policy endeavors.

Second, there did look to be a modest effect on reducing important outcomes. And, these were driven mostly be moderate-risk (not high-risk) patients. This argues for a heterogenous treatment effect based on co-morbidity.

Third, the statistically significant increase in all-cause hospitalizations in the intervention arm suggests that more aggressive attempts at blood pressure and cholesterol levels may have risen the risk of off-target ill effects.

In the end, Andrew felt like the study was a wash. He did not feel strongly that the Million Hearts endeavor made a real difference.

Comments on our Audio— I think we misspoke about the patient years. We said per 100,000 patient years. It was 1000 patient years. I also think we misspoke about deaths being similar. It was actually slightly lower in the intervention arm.

Recall that Sensible Medicine remains a subscriber supported site. Thanks for your generous support. We are excited to bring you content that can’t easily be found elsewhere. I have an excellent recording to post soon on screening for atrial fibrillation.

Friday Reflection 31: Senses, Memories, and Medicine

Medical training introduced me to a whole menu of smells -- both diagnostic tools and reminders of times in my career.

Sudden cardiac death due to ventricular rhythm disturbances are rare but highly public. It’s strange and curious because you don’t expect healthy athletes to suffer serious cardiac issues.

Recently three prominent athletes have survived sudden cardiac death. Christian Erikson, a Danish soccer player, Damar Hamlin, an American football player and Bronny James, son of Lebron James. These high-profile cases have highlighted the issue of sudden cardiac death of athletes.

Dr. Dorian has published extensively on this topic. We had a great conversation. I learned a lot and hope you will too.

JMM

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Here are three pertinent articles he has published—note the first is from NEJM.

Landry CH, Allan KS, Connelly KA, Cunningham K, Morrison LJ, Dorian P; Rescu Investigators. Sudden Cardiac Arrest during Participation in Competitive Sports. N Engl J Med. 2017 Nov 16;377(20):1943-1953. doi: 10.1056/NEJMoa1615710. PMID: 29141175; PMCID: PMC5726886.

Weissler Snir A, Connelly KA, Goodman JM, Dorian D, Dorian P. Exercise in hypertrophic cardiomyopathy: restrict or rethink. Am J Physiol Heart Circ Physiol. 2021 May 1;320(5):H2101-H2111. doi: 10.1152/ajpheart.00850.2020. Epub 2021 Mar 26. PMID: 33769918.

Weissler-Snir A, Allan K, Cunningham K, Connelly KA, Lee DS, Spears DA, Rakowski H, Dorian P. Hypertrophic Cardiomyopathy-Related Sudden Cardiac Death in Young People in Ontario. Circulation. 2019 Nov 19;140(21):1706-1716. doi: 10.1161/CIRCULATIONAHA.119.040271. Epub 2019 Oct 21. PMID: 31630535.

Angela Lu is training to be a physician. She’s interested in public policy. As a third year medical student, she teamed up with established leaders to ask a unique question regarding public disclosure of financial relationships.

When the Centers for Medicare & Medicaid Services (CMS) issues National Coverage Determinations (NCDs) for services or products, they mean business. Such decisions have huge implications. You cannot go against them. Think #HighConsequences.

CMS studies the evidence and publishes a proposed decision. It then allows public comments. People care.

The idea behind their study, which made it into the Journal of the American Medical Association, was to study how many commenters disclosed their financial conflicts.

Dr. Lu went through more than 680 comments submitted on 4 NCDs—all of which were high cost invasive procedures.

I won’t spoil the conversation, but they found a very high percentages of comments asking to expand indications for these procedures and very very low percentages of people who disclosed their relevant relationships. This study was made possible by the Open Payments database.

One important note: disclosure of relationships was voluntary. Enjoy the conversation. Thanks for listening. JMM

Andrew Foy rejoins the Sensible Medicine podcast. We talk first about coronary artery calcium. Andrew is an expert in this area.

We have co-written our case against CAC scoring for any cause in the American Family Physician. It’s had little effect as CAC scoring is running rampant.

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The second part of our conversation centers on a big med-ed project Andrew is co-leading at Penn State. He calls it Argue-to-Learn.

The idea is to expose pre-clinical students to the value of civil debate. Here is their paper: Student Perceptions of a New Course Using Argumentation in Medical Education

Here is a quote:

The absence of argumentation (i.e., a productive exchange of opposing views aimed at improved understanding of a given issue) in medical education may leave physicians susceptible to medical marketing, and incapable of both resolving industry claims and adapting to changing paradigms.

Gosh. Gosh. Double Gosh, this is an exciting effort. Listen to Andrew explain.

JMM

This week, I talk with Andrew Foy, who is an academic cardiologist at Penn State University in Hershey, PA. Andrew is one of the smartest voices in medicine today.

We start with the REMEDIAL trial, published recently in JAMA. Ablation vs Meds. Primary endpoint—depression and anxiety. One of the main issues was the control arm—namely that there was no sham control.

We referenced this useful review paper on placebo and nocebo effects in cardiology, from Brian Olshansky.

Our second topic was the FRAIL AF trial.

This was frail, elderly patients who had AF and were stable on Vitamin K antagonists (similar to warfarin) were randomized to remain on the VKA or switch to a direct acting oral anticoagulant. Primary endpoint—major bleeding.

FRAIL AF is in Andrew’s wheelhouse as one of his primary academic areas of study is the role of multi-morbidity in translating medical evidence.

He mentions a term called heterogenous treatment effects or HTE. I don’t love the term because it’s heavy into jargon. But HTE is super important for using evidence in the clinic. Andrew explains it well.

Here is the editorial Andrew co-authored regarding another important trial in elderly patients who were having NSTEMI.

I have written about FRAIL AF on Medscape and Sensible Medicine.

We were going to talk about coronary artery calcium screening, but we had talked enough and will do a separate podcast on CAC.

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As always, let us know what you think. We appreciate the support. Thank you. JMM

Sensible Medicine

Sensible Medicine x Vaccine Curious Cross Podcast on the USA vs Denmark, vaccines, etc:

Show notes by Dovid Y Rimmer, Tracy Beth Høeg and Christine Stabell Benn

* Benn, Høeg. Regarding becoming a medical skeptic. Hoeg: anonymous blog - exercise during pregnancy. Benn: Vitamins, sex differences, and vaccines.

* Differences in pandemic response between Denmark v. California - school reopening, masks.

* USA recommends boosters (yearly) for Children, Denmark does not recommend vaccinating children <18 at all for covid..

* Benn: Op-ed recommending gradual herd immunity.

* Høeg, Duriseti, Prasad NEJM letter: Observational data for Covid mortality in vaccinated + boosted population (Source the original study, raw data release in response to letter, and Prasad NEJM letter).

* Chandra & Høeg reanalysis of MMWR study: Differences in Covid-19 between schools mandating masks and not mandating. MMWR did not publish reanalysis, published in Journal of Infection.

* Høeg et al reanalysis of Cowger et al. in NEJM, differences between schools mandating masks and not mandating in Boston, MA.

* Six Clalit Health studies from Israel published in prestigious medical journals - the studies did not release their data or analyses to the public. (What were the points they made that influenced policy decisions, where were they cited, altimetric score. i.e. note that they were effective influencing policy without transparency).

* Childhood vaccination schedules: Denmark 18 doses and USA 50 doses vaccination schedules. Note: differences regarding Influenza, Hep A & B, Varicella, Meningococcal, and Covid-19 which may be added to a yearly schedule. Denmark and Sweden don’t recommend yearly influenza vaccine in non high-risk under 65. 

* Denmark requires benefit for children, Finland allows societal considerations such as socioeconomic component of rotavirus. Finland uses influenza vaccine. And Denmark might introduce flu vaccine to reduce the flu burden on the elderly.

* Ethics of consequentialist vaccine policy.

* Pandemrix Swine flu vaccine had an adverse effect event of narcolepsy (hundreds of children affected), Denmark was spared some of the consequence by limiting its recommendation to vulnerable children only.

* Flu deaths approximately 2-4/million, amongst children (Norway, US).

* Nordic countries were hesitant to recommend routine Covid-19 vaccination. Denmark admits it was a mistake to recommend vaccinating children (it was done for the adults and since the vaccine was leaky it made no difference, everyone got it anyway).

* Norway found in their pandemic investigation 6 weeks school closure was ‘a mistake’.

Key academic claims:

* Benn paper on Covid-19 becoming a childhood disease.https://www.bmj.com/content/374/bmj.n1687/rr-8 

* Benn: Predictably Covid-19 would be dangerous only to old, vulnerable, and those with a large viral inoculum.https://pubmed.ncbi.nlm.nih.gov/32146445/ and https://pubmed.ncbi.nlm.nih.gov/6741923/ 

* Benn: Non-trivial C19 Death amongst elderly, but it probably didn’t change the amount of years they lived. https://pubmed.ncbi.nlm.nih.gov/33137809/ 

* The greater the inoculum the more harmful the disease. Example: measles index cases v. https://pubmed.ncbi.nlm.nih.gov/6741923/ 

* Covid-19 harms, are rare in children. Actual risk to children prior to natural immunity and afterward (Ideally include all risks, Death, hospitalization, severe disease). ​​https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9613797/, risks of severe disease https://pubmed.ncbi.nlm.nih.gov/35962242/ 

* Even rare harms would outweigh the benefits of widespread childhood vaccination. https://www.bmj.com/content/374/bmj.n1687/rr-8

* Amongst most viruses the 2nd infection is less pathogenic.

* Harms of lockdown exceeded benefits in quality studies, some non quality studies might indicate otherwise. https://www.tandfonline.com/doi/full/10.1080/00779954.2020.1844786?src=recsys, https://www.tandfonline.com/doi/abs/10.1080/13571516.2021.1976051 

* Measles index cases (Child contracts the virus at school) results in more mild disease, family transmission is more severe with 4x fold mortality. https://pubmed.ncbi.nlm.nih.gov/6741923/ This has also been shown in animal studies https://pubmed.ncbi.nlm.nih.gov/36992457/. Epidemiological studies: Secondary cases (Family transmission) for Pertussis, https://pubmed.ncbi.nlm.nih.gov/11798255/ Varicella https://pubmed.ncbi.nlm.nih.gov/15702036/  and other viruses are worse than index cases i 

* Hoeg: MMWR School transmission of c19 is rare: https://www.cdc.gov/mmwr/volumes/70/wr/mm7004e3.htm 

Although it is unoriginal to point out that doctors learn from our patients, here are a few lessons so powerful, so extrapolatable, that I forever associate them with an individual.

Here is the profile for Harvard Professor Robert (Bobby) Yeh.

His most recent Circulation paper: Bringing the Credibility Revolution to Observational Research in Cardiology.

We referenced a paper by Professor Miguel Hernan: The C-Word: Scientific Euphemisms Do Not Improve Causal Inference From Observational Data

Paper referenced on left ventricular assist devices: Comparative Effectiveness of Percutaneous Microaxial Left Ventricular Assist Device vs Intra-Aortic Balloon Pump or No Mechanical Circulatory Support in Patients With Cardiogenic Shock

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I learned a lot from this conversation. One of the main lessons is that no matter how well the authors avoid causal language, the intent of an observational comparison study is causal. And if that is so, the main thrust of these efforts ought to be simulate, as close as possible, a randomized clinical trial.

One of my favorite parts of our chat was Bobby’s now famous explanation of immortal time bias using Cheetos.

Let us know what you think. I hope to do more of these types of conversations.

JMM

BW was a 66-year-old woman who presented for an urgent visit to the general medicine clinic. She reported that she had been having dizziness for the last four days. When pressed, she said it occurred intermittently, being present more than absent. She could not identify any palliative or provocative features, and when asked about associated symptoms she said that she felt “bad and scared” when it was present. The doctor encouraged her, many times, to characterize the dizziness, and she could only say that when she had it, she felt dizzy.

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Many a medical trainee has been humiliated on morning rounds after proclaiming that their presentation was wanting because the “patient was a poor historian.” Any attending worth her white coat will respond in one of the following ways:

“There are no poor historians, just poor history-takers.”

“You do realize, don’t you, that the patient is not the historian? You are the historian.”

“Did you consider the differential diagnosis of why you were unable to obtain a useful history?”

I admit that, going for pith over constructive criticism, I employ the former two more than the latter one. There is a differential diagnosis for the patient who cannot describe the history of their medical concerns.

Often, the inability of a doctor to obtain a history is actually a physical exam finding – an extremely non-specific finding, but a finding nonetheless. Psychiatric disease, dementia, and delirium (whose differential diagnosis itself is practically a textbook of medicine) will render a patient unable to provide an accurate history. I can recall dozens of “poor historians'' who became Robert Caro-esque once their hypercapnea, uremia, or alcohol withdrawal was treated.

There are three other reasons that obtaining reliable and informative histories might be a struggle.

1.      We think with language

The first — the saddest, most troublesome, and probably most common – reason that patients are unable to provide a reliable history is because of their impaired language skills. Not only do we use language to communicate, we also use language to think. George Orwell wrote, “…if thought corrupts language, language can also corrupt thought.”[i]

Those of us who failed to master language, usually through inadequate education, are unable to express their health concerns clearly. Sometimes, listening to a patient try to describe symptoms, I get the sense that the problem is more than expressive.

BW was not an especially striking example of this for me, she was just one of the more recent. She also presented with a problem for which an accurate history is critical. The history of a patient's dizziness radically alters the differential diagnosis. We teach trainees that the first question to pose to a patient with dizziness is, “What do you mean, dizzy?” We tell the trainee to ask the question and then sit back and listen. More often than not, patients will describe their dizziness in a way that can be interpreted as lightheadedness, vertigo, unsteadiness, or a non-specific feeling of being unwell.[ii]

As I interviewed BW, my sense was that she not only struggled to articulate what she was feeling but to figure it out herself. Beyond my frustration in having trouble caring for her, I considered the lifelong impact of leaving people educationally impoverished. Sure, we limit people’s earning potential, but we also limit their internal life and their healthcare.

2.      Anxiety affects how we experience symptoms

VG is a patient I have seen for years, from his mid 30’s to his early 60’s. He has a few very mild chronic medical conditions and very severe anxiety disorder. He is a successful professional but struggles with intermittent episodes of health-related anxiety.

Our interactions usually begin with an email or a phone call. VG will have become anxious about a new symptom. The symptom is real – joint pain, a rash, a new floater. The symptom has generated a web of worry about what it could portend. The worries are always baseless and would be amusing if they were not so clearly painful and disturbing to him.

I have learned that for VG, as well as for many patients like him, these concerns require a visit. An accurate history cannot be obtained without seeing him. The anxiety clouds VG’s experience of the symptom. The knee pain becomes excruciating, the rash ubiquitous, the floater debilitating. The response to simple questions -- Is the knee pain worse coming down the stairs? Where is the rash? Do you see the floater in one or both eyes? -- become unreliable. Seeing VG, providing some reassurance, and obtaining objective physical data is imperative.

3.      Secondary gain

“Listen to your patient; he is telling you the diagnosis” is is an Osler (or merely Oslerian) quotation. From the earliest days of our training we are taught to listen to our patients and believe what they are telling us. Our greatest sin in history taking is that we interrupt too soon and too often. We ask closed-ended and leading questions. When the answer to a question doesn’t align with our hypothesis, we either ignore the response or doubt its veracity.

However, patients are people and people lie. Patients exaggerate the symptoms of their sinus infection to get an antibiotic prescription. Patients tell you that their oxycodone or Ambien fell in the sink or toilet so they can get an early refill.[iii] I have had numerous people appear on my schedule with the chief concern of “chest pain” documented by the nurse. When I ask, “Tell me about your chest pain?” the patient responds, sheepishly, “I’m not actually here for chest pain but I really needed to see you and I knew that would get me in.”

Some of these untruths are the proverbial chickens coming home to roost. Patients exaggerate symptoms because they fear they will not otherwise be taken seriously. They fear mild but troublesome or worrisome symptoms will be met with:

“Let’s just watch that.”

“That doesn’t really sound like it warrants treatment.”

“If it hurts to bend your arm, don’t bend your arm.”

Most everyone learns at some point the factoid that 80% of diagnoses come from the medical history. However, contrary to a standardized test on which the medical history is presented in a paragraph of clean prose, it requires skill to obtain a medical history. A novice will take longer than an expert to extract a less accurate history. From some patients, however, not even an experienced physician can obtain a cogent medical history. This failure may be a clue to an underlying diagnosis. It may also be related to a person's education, their health-related anxiety, or their effort, conscious or unconscious, to influence the doctor. 

[i] Orwell obviously took this idea to in a frightening direction in 1984 describing a government that uses the control on language to control thought.

[ii] We often jokingly describe this last type of dizzy as “dizzy dammit” – as in “I am just dizzy, dammit.”

[iii] It is interesting that people only drop opiates, benzodiazepines, and stimulants in the sink. Nobody has every dropped an SSRI, statin, or antibiotic.

There is something valuable about learning to adapt old skills to novel situations.

Adam and I discuss three topics

I) The MIND Trial published in NEJM. Does a special diet reduce the future risk of cognitive decline?

II) HFpEF — I am speaking at a congress on heart failure with preserved ejection fraction this week, and Adam helps me out with some pointers.

III) NYT published a Sunday front page story on potential overuse of procedures for peripheral artery disease.

JMM

Four pieces of advice nobody asked for. 

KW was a 58-year-old man with long standing type 1 diabetes mellitus and hypertension. He came to an appointment one Friday afternoon with chest pain. The pain had been present intermittently for 10 days. It was on the left side of his chest and beneath his sternum. It did not radiate anywhere, it was not related to exertion, nor was it associated with diaphoresis or shortness of breath. It was also not positional and there were no areas of tenderness.

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When I was a kid, we often played “Would You Rather?” to pass the time during a car or bus ride. This game had remarkable staying power. When we first started playing, at about age ten, the questions were mostly things like:

Would you rather eat a cicada or a cricket?

As we aged, the questions progressed through the usual male adolescent fare to more profound philosophical quandaries:

If you managed the Mets, would you rather pitch Seaver or Koosman?

Would you rather have a Ferrari or a Porsche?

Would you rather date Lauren or Lizzie?

Would you rather visit the past or the future?

From a professional standpoint, there is no question that my answer to the final question would be, “the past.” There are a dozen or so patients that I want a second chance at. I wonder if, knowing what I know now, would I manage things differently?[1] Would the outcomes be different? Would some of the people still be here?

I should not have admitted him.

            For my entire career I have had a clinic scheduled on Friday afternoon. My reasoning is two-fold. First, I know that if I didn’t have patients scheduled Friday afternoon, I’d probably kick off early. Having a full schedule on Fridays assures that I stick it out to the bitter end, thus making me more productive each week. Second, most people opt not to see patients Friday afternoon so I tend to get more support as one of the few doctors working.

            The downside of this is that I am seeing patients when my management options are somewhat limited. Patients present with troublesome symptoms that they “just want checked out before the weekend” and I’m left either worrying about them all weekend or admitting them to the hospital where I know little will happen for the next two days.

            There was a lot about KW’s chest pain that was not concerning for symptomatic coronary artery disease. It was not exertional. The episodes sometimes lasted minutes and sometimes hours. It was not accompanied by shortness of breath, diaphoresis, or a feeling of impending doom. He also had had a normal stress test a couple of years before.

            On the other hand, KW was a middle-aged American man with chest pain and significant risk factors for coronary artery disease – hypertension and diabetes – neither of which had ever been terribly well-controlled.

            I made the decision that I felt was safest for him and the one that would let me sleep best all weekend; I admitted him to the hospital. I called the admitting resident; I let her know that I was (a little) worried that he had unstable angina and that I was admitting him so that he could be observed until he could get an assessment of his coronary arteries.

The resident (not incorrectly) decided that if he might have unstable angina, he should be started on a blood thinner – heparin.

In the end, KW did not have unstable angina, a coronary angiogram done weeks later was normal. Why did it take weeks to complete the angiogram? Because after being started on heparin, he had an intracranial hemorrhage – a bleed in his brain.

I should have admitted her.

PH is a woman I have written about in the past. She presented to me early in my career having lost about a third of her body weight to an undiagnosed, metastatic cancer. She did not require hospitalization. She was well hydrated and her vital signs were normal. She had walked into the office that first day and would need only a wheelchair to come and go to her last visit 6 months later. She did not require hospitalization for evaluation or treatment. There would be little we could offer her beyond the palliative care that I could direct at her home.

I managed her evaluation and her care while she remained an outpatient. By the time she died, this management had included intravenous fluids, pain medications, antiemetics, and seizure medications. My memory was that what drove my effort to keep her out of the hospital was more my philosophy than her and her family’s wishes. At the time, I believed that unnecessary hospitalizations were an anathema. They wasted money, put patients at risk, and were the refuge of lazy or unskilled physicians. I do remember that PH wanted to avoid aggressive care, but I cannot remember her explicitly resisting hospitalization. I do remember her brother once asking, “Shouldn’t she be in the hospital?”

From my current vantage point, my efforts to keep her out of the hospital seem, at best, ill-advised. It seems my management decisions were more about me and less about her. It is hard to imagine that the experience, for PF’s family if not for her, would have been less stressful had I brought her into the hospital a few times during her final months.

Did I miss something simple?

            JJ was the rare patient who I saw for decades whose health was at its worst when I first met her. She presented to my clinic in a heart failure exacerbation. I wheeled her to the emergency department where she was promptly intubated. Over the next 20 years her heart failure became asymptomatic; her asthma – which I am pretty sure was misdiagnosed heart failure – disappeared; and I weaned her off all her drugs for diabetes. She and her family marked the date of our first visit as a second birthday and saw every year after this date as an unexpected gift.

            In her mid-70s, at a routine appointment, she mentioned an episode of vomiting followed by transient loss of consciousness. The episode barely troubled her and a brief evaluation at the visit was unrevealing. Three months later she died unexpectedly after a similar episode. The differential diagnosis of what I might have missed is extensive. I wonder if I could have made a diagnosis, the treatment of which might have saved her life.

Did I miss something complicated?

            SV was a patient who kept me up at night for the better part of 18 months. She was in her late 70’s and she was dying. There was fatigue, weight loss, nausea, declining kidney function, and a few strokes. My work up was extensive including imaging, blood tests, and biopsies. I consulted a cardiologist, a neurologist, a nephrologist, and a rheumatologist. We treated many disparate issues but never discovered the unifying diagnosis that eventually took her life. Knowing what I know now, and having the diagnostic tools that now exist, could I have saved her?

Could I have convinced her to get treated?

TP was 80 years old when I diagnosed her with breast cancer. Long before we met, she had decided that she would never have a second mammogram. I did not set out to find a tumor. I discovered a breast mass when she came to see me with shingles.

You might be thinking, how can you be sad that you did not convince an 80 year old with cancer to be treated. Especially when this woman did not want to be treated? Well, first, 80 years old is not the same for every person. Everyone who met TP assumed she was at least 15 years younger than she was. Because she had no intention of getting treatment, she declined biopsy or evaluation of her cancer. I knew nothing about the biology of the cancer or the extent of the disease when I discovered it.

Over the next 5 years, this vibrant woman declined in the most unpleasant and traumatic ways. I have to think that treatment could have made her life better if not longer. I wonder if I am now better equipped to counsel her.

Could I have convinced him not to get treated?

KS was a man in his early 80s. He had COPD and depended on home oxygen. His symptoms were pretty well controlled on a regimen of inhalers. He continued to smoke, saying – with a wink – that it was his only pleasure left in life. He was adamant about not wanting screening tests or any medications not necessary to relieve symptoms. During my one attempt at discussing end of life planning, he told me he just wanted to make sure he “went fast and without pain.” I documented those words in my progress note that day.

Then, everything changed.

KS came to the office after starting to notice streaks of blood in his sputum during his morning coughing spells. A chest x-ray that day revealed a left upper lobe mass. I told him that this was almost certainly lung cancer, and offered him two paths forward. The one I expected him to take was to assume the diagnosis was lung cancer, forgo further workup and therapy, and treat symptoms as they arose. The option I expected him to decline was further evaluation with a CT scan, biopsy of the most accessible lesion, and a visit to a surgeon and/or an oncologist. His decision surprised me.

He was soon diagnosed with small cell lung cancer with regional spread. After meeting with an oncologist he opted for chemotherapy. His reasoning was, “I feel pretty good now, and if I’m going to be dead in six months with or without treatment, I’m hoping treatment will give me a better six months.” I reminded him of what he had said in the past about how he imagined the end of his life playing out, but he would not really engage in this conversation.

The next 9 months were marked by 9 hospitalizations. KS died during the final one when his inpatient team failed to resuscitate him after a cardiac arrest. He had declined hospice care until the end and would not even accept “do not resuscitate” status.

I never could figure out what was behind his change of heart. I wonder, if I had a second chance, if I could get him to discuss his decision making and, maybe, figure out a way to achieve a more humane end.

[1] Just because every time I read this sentence the lyrics to two songs come to mind I have to reference them here. (This is the beauty of writing for substack rather than a journal where no editor would ever let this through). Can you guess the songs?

First, Bob Dylan:

“I was so much older then, I’m younger than that now.”

Second, The Faces:

I wish that I knew what I know nowWhen I was youngerI wish that I knew what I know nowWhen I was stronger.

This ghost panel is made up of people who used to be my patients but no longer are — people who left my practice without telling me. 

Links

The Case for Being a Medical Conservative https://www.amjmed.com/article/S0002-9343(19)30167-6/fulltext

ELAN Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2303048

Mandrola on NYC Residents’ Strike https://www.medscape.com/viewarticle/992607

I visit the binder to pay my respects, to learn, to reminisce, and to trace the arc of my career.

Medicine in America will be better, more humane, and more affordable with more good, smart, dedicated primary care physicians. Be part of the solution. 

Why did it take years for me to reach a time in my career when I am comfortable admitting knowledge gaps?

When patients meet a new doctor, both patient and doctor should be aware of each other’s philosophy. 

Chat GPT - Medical Journals - Preventive medicine

Mandrola, Prasad and Hoeg are back to talk about a new exercise study— can you do too much— and then COVID19 pandemic errors.

Prasad, Cifu, Mandrola, Hoeg, Makary are back for a discussion. Next week we will only have 3 guests.

Check out this all star line up

Cifu/ Mandrola/ Hoeg/ Foy/ Damania/ Prasad - talk about equipoise, randomization, and more

A Guest Friday Reflection: On Death and Its Futility