Posts in: medicine

Back to school

It will be 13 years this June since I have left a job teaching histology at the University of Belgrade to start internal medicine residency in Baltimore. And lo and behold, I am back teaching, sort of.

UMBC — University of Maryland Baltimore County to friends — is starting a graduate course on clinical trials. I will be helping out Wilson Bryan, the recently retired Director of FDA’s OTAT (aka “head of cell and gene therapy”), to design and run it. Maybe even do a lecture or two. The two of us talked briefly about the new course on a UMBC podcast, This is also where I learned what my title would be. Graduate instructor, apparently. The amount of paperwork required was not commensurate with the title. Oh my, all that docusigning… which is out today.

The course will be an in-person/on-line hybrid, so even those not in the area — and it will be held at UMBC’s Shady Grove campus — may join this coming September. From what I understand, giving people who are not physicians the opportunity to learn about designing, running, and interpreting clinical trials is a rarity, so it will be interesting to see who shows up and where the discussion leads us.

So, 13 years… Different university, different subject matter, but how much could things have changed since then anyway?

As two of our three offspring lay in bed with fevers, a thought comes to mind: could covid have caused this never-ending chain of infections which began last fall, during which a week rarely goes by in which no one misses at least one day of school because of illness? Has it destroyed our immune systems, made us more susceptible to other infectious diseases? There is, after all, no end to articles in press both professional and lay which warn of long-term effects of SARS-CoV-2 on various lymphocyte subsets.

Well, no. Or at least highly unlikely. A 5-person household with three school-aged children will have one respiratory virus or another circulate a full two thirds of the year. With our youngest starting PK3 last fall, we have become that household, and 65% sounds about right.

Woe to us and anyone who visits our little Petri dish.

And in some positive news — can you imagine those still exist? — the US Food and Drug Agency has issued their draft guidance on decentralized trials (PDF download). America is playing catch-up with the UK in this regard, but better late than never!

May lectures of note

  • Speakers: Sam Mbulaiteye, MBChB, M.Phil., M.Med.; Swee Lay Thein, B.S., F.R.C.P., F.R.C.Path., D.Sc., FMedSci
  • Wednesday, May 10 2023, 12pm EDT
  • Watch here

Diabetes Mellitus: Great Progress; Diabetes: The Marathon of Life

  • Speakers: Douglas Melton, PhD; Courtney Duckworth, MD
  • Tuesday, May 16 2023, 4pm EDT
  • Watch here

Is Cerebrovascular Disease Ever Really Silent? Stroke, Small Vessel Disease, and Cognition

  • Speaker: Rebecca F. Gottesman, MD PhD
  • Wednesday, May 31, 2023 12pm EDT
  • Watch here

April lectures of note

The first good one is tomorrow!

Demystifying Medicine - How is the Brain Organized and How Does it Work?

  • Speakers: Nelson Spruston, PhD, Janelia HHMI and Marcus Raichle, MD, Washington University
  • Tuesday, April 4, 2023, 4:00:00 PM EDT
  • Watch here

Ethics Grand Rounds: Is it Ethical to Appeal to Research Participants’ Altruism?

  • Presenter: Beth Kozel MD, PhD Lasker Clinical Research Scholar, NHLBI Discussant: Alex Voorhoeve PhD Head, Department of Philosophy, Logic and Scientific Method, London School of Economics
  • Wednesday, April 5, 2023, 12:00:00 PM EDT
  • Watch here

Clinical Center Grand Rounds: From Bench to Bedside: A Translational Approach to Innovation in Research and Treatment of Perinatal Depression

  • Speaker: Samantha Meltzer-Brody, MD, MPH, UNC Center for Women’s Mood Disorders, Department of Psychiatry University of North Carolina at Chapel Hill
  • Wednesday, April 12, 2023, 12:00:00 PM EDT
  • Watch here

Demystifying Medicine - Fat: Biology and Staying Thin

  • Speakers: Aaron Cypess, MD, PhD, NIDDK, NIH and Kevin Hall, PhD, NIDDK, NIH
  • Tuesday, April 18, 2023, 4:00:00 PM EDT
  • Watch here

The Popperian Podcast:

Interviewing academics, professionals and other experts, The Popperian Podcast is a monthly podcast where Jed Lea-Henry looks into the philosophy and life of Karl Popper.

The latest episode, about medical discovery, pairs nicely with Against Method.

For your weekend reading enjoyment, FT’s Janan Ganesh on (un)healthy eating:

  • It is easier to fast than to eat healthily.
  • You must be willing to upset people.
  • Beware pasta.
  • Don’t expect to “burn it off”.
  • Know thy weight.

Sound advice. I may have also posted a few excerpts.

BS bonanza

Doximity is beta testing ChatGPT for doctors:

Physicians can use the free DocsGPT to prepare referrals, certificates of medical necessity and prior authorization requests or to write a letter about a medical condition. A growing menu of prompts offers many options, and users can type in a custom request.

Next up: medical insurance companies using their own AI to process the AI-generated BS they receive from healthcare workers into something more easily understandable.

At least the economists must be happy!

March lectures of note

Available to general public!

ChatGPT and Potential Healthcare Implications of Large Language Models

Tests for Early Cancer: Facts vs. Opinions Can We Detect Early Cancer?

It’s a Bacterial World

Bias of the day: immortal time

This is when you do a retrospective study, select cohorts according to exposure, but measure outcomes — usually death, or hospitalization, or something else bad — in a way that guarantees one or more of the cohorts have a period of time when that outcome couldn’t have happened. That’s how you get “immortal”, or “guaranteed” time.

Three classic examples: Courtesy of Bing.

  • A study that evaluated the hypothesis that menopause occurring before age 40 years is associated with the development of cardiovascular disease (CVD). The study counted women who had premature menopause as exposed to CVD risk from their date of birth, ignoring the fact that they could not have developed CVD before menopause.
  • A study that assessed the effect of statins on diabetes progression and insulin use. The study classified patients as statin users based on their first prescription after hospital discharge, but included the time between discharge and prescription as exposed time, even though they were not taking statins during that period.
  • A study that examined the association between beta-blocker use and mortality in patients with heart failure. The study defined beta-blocker exposure based on pharmacy claims after hospitalization, but did not account for the time lag between hospital discharge and drug initiation, which could have biased the results in favor of beta-blockers.

To these three classics we can now add two more, one highly publicized, the other less so, both surprising considering the journals and the supposed peer review they must have gone through:

  • A study that compared hospitalization rates of those who had a positive SARS-CoV-2 test and did not take the Covid-19 drug Paxlovid to those who took Paxlovid regardless of test status. The study counted the day of the positive test as “Day 0” for the untreated cohort; however, for patients who started taking Paxlovid and did not have records of a positive test “Day 0” was one day before treatment start. See this Twitter thread for relevant excerpts and a more detailed explanation. As the study excluded patients who were already hospitalized when they started Paxlovid, but included untreated patients who had a positive test and were hospitalized on the same day, this guaranteed 1 day of “immortal time” for the Paxlovid cohort.
  • A study that used “real world data” to compare standard blood thinners to a procedure called left atrial appendage occlusion (LAAO) for prevention of death and stroke in patients with atrial fibrillation. However, patients who underwent LAAO had to live long enough with atrial fibrillation without getting a stroke to “graduate into” the procedure. Not only is immortal time here so glaring, the study is eerily similar to the original heart transplantation study in which this bias was first identified.

Cardiologist John Mandrola explains in depth why the LAAO paper, and the way it was spun, is particularly egregious.

Note that this is only a problem in retrospective — or, how they now like to be rebranded, “real-world” — studies. As the most recent cases show, these are not only worthless for informing anyone’s real-world decision, but also contribute to the noise, the chaos, and the general fear-uncertainty-doubt of medicine. A voluntary moratorium would not be out of line.