The Curbsiders Internal Medicine Podcast

Episode 506 DIGEST-Hotcakes: PSA Screening, Acetaminophen and Autism, COVID-19 Vaccines and Cancer, Aspirin and Anticoagulation in Coronary Artery Disease

Date: December 1, 2025

Episode Overview

This Curbsiders Digest episode brings together multiple team members and special guest Dr. Adam Sifu (University of Chicago, Sensible Medicine) for critical roundtable discussion of four high-profile studies that have hit the internal medicine literature and the public sphere. Covering prostate cancer screening, acetaminophen safety in pregnancy, cancer risk after COVID-19 vaccination, and aspirin with anticoagulation in coronary artery disease, the group dissects evidence, clinical implications, and messaging—balancing critical appraisal with Curbsiders’ trademark humor and candor.
The core aim: To assess whether the latest buzzworthy studies should (or shouldn’t) change internal medicine practice, and why.

Key Discussion Points and Insights

1. Should We Still Be PSA Screening? — ERSPC 23-Year Follow-Up

Lead Discussant: Dr. Nora Taranto
Segment Start: [04:16]

Study Details

• European Randomized Study of Screening for Prostate Cancer (ERSPC)
• 23-year follow-up; randomized men 55-69 to PSA screening vs. no invitation
• Main outcome: Prostate cancer-specific mortality

Core Insights

• PSA screening group had a 13% relative reduction (absolute reduction 0.22%) in prostate cancer mortality compared to controls.
• Number needed to screen (NNS) to save one life: 456; for every life saved, 11 extra men are overdiagnosed.
• Massive overdiagnosis/ overtreatment remains a dominant concern.
• Changes in management (active surveillance, MRIs) may reduce overtreatment compared to the study era, but whether this improves balance of benefit/harm is unproven.
• Guidelines remain conflicted; current practice relies on shared decision-making rather than blanket screening.
• Practical barriers: Most patients default to accepting screening; in practice, counseling may be perfunctory.

Notable Quotes

• “This is the last time we’ll have to deal with a prostate cancer screening trial... you could never redo this study. So at least like we’ll never have to talk about this again.”
  — Dr. Adam Sifu [09:25]
• “For every 12 men diagnosed, we save one from prostate cancer death. That means that 11 out of 12... I harm rather than help.”
  — Dr. Adam Sifu [15:07]
• “It's a conversation as opposed to a mandate.”
  — Dr. Nora Taranto [21:51]

Practice Impact / Hotcakes Rating

• No guideline or practice changes anticipated.
• Decision to screen remains individualized based on patient discussion.

2. Acetaminophen in Pregnancy and the Autism Risk: Controversy & Causation

Lead Discussant: Dr. Rahul Ganatra
Segment Start: [25:17]

Study Details

• Systematic review (Prada et al., Environmental Health); 46 observational studies; associational data only
• FDA recently changed label to recommend caution with acetaminophen in pregnancy

Core Insights

• The review found a weak association, but no credible evidence of causation.
• Many methodological weaknesses: heterogeneity of exposure definitions, huge potential for confounding by indication (fever, infection), no meta-analysis.
• Causal claims and public health recommendations in the study and FDA communication far outstrip the actual evidence.
• Largest included sibling study (JAMA) demonstrated no association after accounting for genetic/environmental confounding.

Notable Quotes

• “This is like the greatest editorial failure ever... to make the jump from association to causation and action is appalling.”
  — Dr. Adam Sifu [28:34]
• “[There is] a dearth of high quality evidence to inform what pregnant women should do... There are clear harms to alternatives, and harms to maternal fever too. This is not practice changing—if anything, it’s a cautionary tale.”
  — Dr. Rahul Ganatra [39:52]

Practice Impact

• No change in approach to recommending acetaminophen in pregnancy.
• Advise discussion with a healthcare professional per longstanding guidance.

3. COVID-19 Vaccines and Cancer Risk: A Statistical Mirage

Lead Discussant: Dr. Adam Sifu
Segment Start: [44:07]

Study Details

• Korean cohort study; 2.4 million vaccinated, 0.6 million unvaccinated; looked for new cancer diagnoses 1 year post-vaccine.

Core Insights

• “Increases” seen in 6 cancer types for vaccinated patients (HRs up to 1.7 for prostate) reflect strong detection/surveillance bias, not a biological effect.
• No plausible mechanism for true increased cancer within months post-vaccination; early curve separation strongly suggests bias.
• Higher screening propensity, not vaccination, likely drove findings.
• Study and journal are criticized for lack of methodological rigor and for fueling misinformation.

Notable Quotes

• “I think it becomes very clear that what we’re doing is comparing people who went to the doctor, got screened for cancer and often also got a COVID shot, with people who didn’t see a doctor, didn’t get screened for cancer and also didn’t get a COVID shot.”
  — Dr. Adam Sifu [49:33]
• “I would use this paper maybe as a teaching tool in the future and otherwise ignore it.”
  — Dr. Adam Sifu [54:50]

Practice Impact

• Strong consensus: This paper should not change any practice regarding cancer screening or vaccination.

4. Aspirin and Anticoagulation in Chronic Coronary Syndrome — The AQUATIC Trial

Lead Discussant: Dr. Laura Glick
Segment Start: [55:07]

Study Details

• AQUATIC trial (NEJM), multicenter France, 872 pts with coronary syndrome + oral anticoagulant post-PCI; randomized to aspirin or placebo
• Stopped early: median 2 years, significant increase in major adverse cardiovascular events (mostly cardiovascular death) + tripling in major bleeding.

Core Insights

• Strong evidence that long-term aspirin plus oral anticoagulation is harmful: both increased bleeding and CV death.
• Mechanism of increased CV death unclear (possibly bleeding-induced, possibly other factors).
• This high-risk population least likely to benefit, most likely to be harmed.
• Common real-world practice (dual/triple agents) is unsupported by robust evidence and should be reevaluated.

Notable Quotes

• “This is frightening...one in 20 people we treat this way, we actually kill.”
  — Dr. Adam Sifu [58:37]
• “As a general internist, man, this is the most important paper I’ve read all year.”
  — Dr. Adam Sifu [59:07]
• “Combination therapy with an oral anticoagulant and aspirin leads to more harm than good. So let’s just stop it and move on.”
  — Dr. Laura Glick [65:41]

Practice Impact

• Strongly practice changing: Stop chronic aspirin when patients are on chronic oral anticoagulation for coronary disease.
• DOAC monotherapy should be the norm post-PCI for chronic management.

Memorable Moments & Humor

• [01:04] Dr. Ganatra delivers the dad-joke punchline (“Herbivore”), setting the light-hearted tone.
• [20:33] Discussion of France’s exclusion from PSA trial (“they just threw out the whole country ... I was amused by that.”)
• [65:10] Playful blame assigned for saving the most practice-changing article for last: “Who on this podcast can we blame for having discussed Tylenol and autism and the COVID vaccine in cancer before we’ve discussed the aquatic trial?” — Adam Sifu
• [66:13] Classic Curbsiders sign-off: “Bringing you a little knowledge food for your brain hole.” — Paul Williams

Segment Timestamps at a Glance

• PSA Screening: ERSPC — [04:16] to [22:22]
• Acetaminophen & Autism: Systematic Review — [25:17] to [40:44]
• COVID-19 Vaccine & Cancer — [44:07] to [55:07]
• Aspirin + Anticoagulation in CAD: AQUATIC — [55:07] to [65:54]

Summary Table: Practice Change Recommendations

| Topic | Practice Change? | Recommendation | |----------------------------------------------|------------------|--------------------------------------------------------------------------| | PSA Screening (ERSPC) | No | Continue shared decision-making, individualized approach; NNS high | | Acetaminophen in Pregnancy (Neurodevelopment)| No | No restriction; discuss benefits and risks as usual | | COVID-19 Vaccine & Cancer | No | No effect on vaccine or cancer screening policy | | Aspirin + DOAC in Chronic CAD (AQUATIC) | YES | Stop chronic aspirin; DOAC monotherapy recommended post-PCI in CAD |

Closing Notes

The panel emphasizes that clear-eyed, methodologically rigorous appraisal is essential for interpreting the newest research buzz, especially when public recommendations outpace the evidence. Practice should change with strong RCT evidence, as in the case of AQUATIC—not on weak associations, no matter how loudly they are publicized.

Final Words:

• “Data trumps theory every day.” — Dr. Rahul Ganatra [60:00]
• “Let’s just stop it and move on.” — Dr. Laura Glick [65:41]
• “Still hungry for more? Join our Patreon...” — Dr. Paul Williams [66:21]

Prepared for healthcare professionals wanting to stay current, critical, and practice-ready—without enduring the ads, intros, or slow news cycles.