Sensible Medicine

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A spirited discussion of craziness in medicine This is a public episode. If you’d like to discuss this with other subscribers or get access to bonus episodes, visit www.sensible-med.com/subscribe

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.Sensible Medicine is a reader-supported publication. If you appreciate our work, consider becoming a free or paid subscriber.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 PainfulAnybody 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 SadWhen 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 EasyI 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. This is a public episode. If you’d like to discuss this with other subscribers or get access to bonus episodes, visit www.sensible-med.com/subscribe

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. Sensible Medicine is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.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 FibrillationHere is Piotr. He works in Rzeszów, Poland. It’s a beautiful city to visit. I once ran a marathon there. JMM This is a public episode. If you’d like to discuss this with other subscribers or get access to bonus episodes, visit www.sensible-med.com/subscribe

We discuss the state of medical education, Harvard music video, causal language at JAMA and more This is a public episode. If you’d like to discuss this with other subscribers or get access to bonus episodes, visit www.sensible-med.com/subscribe

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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. Sensible Medicine is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber. This is a public episode. If you’d like to discuss this with other subscribers or get access to bonus episodes, visit www.sensible-med.com/subscribe

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. This is a public episode. If you’d like to discuss this with other subscribers or get access to bonus episodes, visit www.sensible-med.com/subscribe

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 Sensible Medicine is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber. This is a public episode. If you’d like to discuss this with other subscribers or get access to bonus episodes, visit www.sensible-med.com/subscribe

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. This is a public episode. If you’d like to discuss this with other subscribers or get access to bonus episodes, visit www.sensible-med.com/subscribe

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. This is a public episode. If you’d like to discuss this with other subscribers or get access to bonus episodes, visit www.sensible-med.com/subscribe

This is a public episode. If you’d like to discuss this with other subscribers or get access to bonus episodes, visit www.sensible-med.com/subscribe

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 This is a public episode. If you’d like to discuss this with other subscribers or get access to bonus episodes, visit www.sensible-med.com/subscribe

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.)Sensible Medicine is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber. This is a public episode. If you’d like to discuss this with other subscribers or get access to bonus episodes, visit www.sensible-med.com/subscribe

This is a public episode. If you’d like to discuss this with other subscribers or get access to bonus episodes, visit www.sensible-med.com/subscribe

This is a public episode. If you’d like to discuss this with other subscribers or get access to bonus episodes, visit www.sensible-med.com/subscribe

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. This is a public episode. If you’d like to discuss this with other subscribers or get access to bonus episodes, visit www.sensible-med.com/subscribe

They say dying alone is sad. They also say we all die alone. There is trauma to not dying alone as well.  This is a public episode. If you’d like to discuss this with other subscribers or get access to bonus episodes, visit www.sensible-med.com/subscribe

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 StudySeverity 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 TrialSensible Medicine is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.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. This is a public episode. If you’d like to discuss this with other subscribers or get access to bonus episodes, visit www.sensible-med.com/subscribe

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 ProgramThis 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. Sensible Medicine is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.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. This is a public episode. If you’d like to discuss this with other subscribers or get access to bonus episodes, visit www.sensible-med.com/subscribe