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5. Diagnostic Reasoning and Medical Overuse with Deborah Korenstein, MD

Deborah Korenstein

In this interview, we talk with Deborah Korenstein, MD, about medical overuse and overdiagnosis. We discuss her April 2021 publication in JAMA Internal Medicine, the Accuracy of Practitioner Estimates of Probability of Diagnosis Before and After Testing as well as the diagnostic process, the teachability of diagnostic reasoning, cognitive biases, and other topics. This conversation was recorded on June 7th, 2021.

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If you enjoy this discussion, you may like our conversation with Dan Morgan, MD and Paul Offit, MD

Who is Deborah Korenstein?

Dr. Deborah Korenstein is Chief of the General Internal Medicine Service at Memorial Sloan Kettering Cancer Center in New York. Her clinical work focuses on care to adult survivors of childhood and other high-risk cancers. As a researcher and an educator of physicians in training, she is interested in improving the value of care while minimizing unnecessary and potentially harmful tests and treatments.

To learn more about mitigating medical overuse, check out the ABIM Foundation’s Choosing Wisely campaign and Dr. Korenstein’s project Testing Wisely.

Factoids:

In this week’s episode, we list some factoids on the overprescription of antibiotics for viral URIs, the incidence of incidentalomas, and the detection of PE with high resolution CTA. If you’d like to read the articles from which these factoids were taken, check them out below:

1. 2019 Update on Medical Overuse: A Review in JAMA Internal Medicine

Highlights:

  • Procalcitonin does not affect antibiotic duration in patients with lower respiratory tract infection (4.2 vs 4.3 days)
  • Incidentalomas are present in 22% to 38% of common magnetic resonance imaging or computed tomography studies
  • 9% of women dying of stage IV cancer are still screened with mammography
  • Clinics commonly overprescribe antibiotics (in 39% of all visits, patients received antibiotics)
  • State medical liability reform was associated with reduced invasive testing for coronary artery disease, including 24% fewer angiograms

2. Overdiagnosis in primary care: framing the problem and finding solutions in BMJ (2018)

Highlights:

  • Overdiagnosis is defined as the diagnosis of a condition that, if unrecognized, would not cause symptoms or harm a patient during his or her lifetime
  • Overdiagnosis can harm patients by leading to overtreatment (with associated potential toxicities), diagnosis related anxiety or depression, and labeling, or through financial burden.
  • Many entrenched factors facilitate overdiagnosis, including the growing use of advanced diagnostic technology, financial incentives, a medical culture that encourages greater use of tests and treatments, limitations in the evidence that obscure the understanding of diagnostic utility, use of non-beneficial screening tests, and the broadening of disease definitions.

 

 

 

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4. The Invisible Graveyard: A Conversation with Economist Alex Tabarrok

In this interview, we speak with Professor Alex Tabarrok about what an economist can bring to discussions about the pandemic, the US government’s response to COVID-19, the performance of the FDA and the CDC, regulatory nationalism, the first doses first campaign, and why America should vaccinate the world. This conversation was recorded on May 2nd, 2021.

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Who is Alex Tabarrok?

Professor Alex Tabarrok is the Bartley J. Madden Chair in Economics at the Mercatus Center and a professor of economics at George Mason University. He is the co-author of the popular economics blog Marginal Revolution and co-founder of Marginal Revolution University. He is the author of numerous academic papers in the fields of law and economics, criminology, regulatory policy, voting theory and other areas in political economy. His articles have appeared in the New York Times, the Washington Post, the Wall Street Journal, and many other publications.

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3. When Modern Medicine Goes Too Far: A Discussion with Paul Offit, MD

Overkill by Paul Offit
In this interview, Mitch Belkin and Daniel Belkin talk with Dr. Paul Offit about mRNA vaccine technology as well as a number of topics from his book, Overkill: When Modern Medicine Goes Too Far. We discuss the use of antipyretics to treat a fever, the overuse of antibiotics, vitamin D and C, as well as cancer screening. This conversation was recorded on April 5, 2021. 

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Who is Paul Offit?

Dr. Paul Offit is a pediatrician at the University of Pennsylvania specializing in infectious diseases, vaccines, immunology, and virology. He is the co-inventor of the RotaTeq vaccine for rotavirus, has published more than 130 papers in medical and scientific journals, and he is the author or co-author of books on vaccines, vaccination, and antibiotics. To learn more about Dr. Offit, visit his website.

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2. Metformin and the Biology of Aging with Nir Barzilai, MD

Nir Barzilai

In this episode, we interview Dr. Nir Barzilai. We discuss the field of gero-therapeutics, the hallmarks of aging, and gender differences in aging. We review his work on centenarians and what they can teach us about the genetics of longevity. Finally, we delve into metformin, its use as an anti-aging therapy, its mechanism of action and the TAME trial, on which he is the primary investigator. This conversation was recorded on March 26, 2021.

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Check out the American Federation of Aging, where you can learn more about the latest in aging-related research.

Who is Nir Barzilai?

Dr. Nir Barzilai is the founding director of the Institute for Aging Research and an expert in the genetics of longevity. He is a professor in the departments of Medicine and Genetics at the Albert Einstein College of Medicine. He is the recipient of numerous awards and grants. He has published over 230 peer-reviewed papers, reviews, and textbook chapters. He is also the author of the book Age Later.

What are the Hallmarks of Aging?

Cell – “The Hallmarks of Aging” (2013) 

Abstract: “Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases…These hallmarks are: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication.”

Centenarian studies:

The Longevity Genes Project is geared at understanding which genetic factors contribute to exceptionally long life. The project focuses on Ashkenazi “super agers”–people between the ages of 95 and 112–to determine how their genetics differ from controls without exceptional longevity. In addition, the study follows the children of “super agers” with matched controls.

What is Metformin?

Metformin (Glucophage) is a biguanide that is a first-line treatment for type 2 diabetes. While it has many mechanisms of action, its primary mechanisms of action are believed to be (1)  decreasing hepatic glucose production by inhibiting gluconeogenesis, (2) inhibiting complex I of the electron transport chain, and (3) inhibiting the mammalian target of rapamycin (mTOR) signaling pathway. It is the 4th most prescribed medication in the United States. Metformin use is associated with a reduction in the incidence of cancer. It is also associated with reductions in cognitive decline and Alzheimer’s among diabetics.

If you are interested in learning more about how metformin attenuates the hallmarks of aging, Nir Barzilai wrote a paper in cell metabolism: Benefits of Metformin in Attenuating the Hallmarks of Aging (2020).

UK Study on Metformin:

Mortality in diabetics on metformin vs sulphonylurea monotherapy vs matched, non‐diabetic controls (Bannister, 2014)

Conclusions: “Patients with type 2 diabetes initiated with metformin monotherapy had longer survival than did matched, non‐diabetic controls. Those treated with sulphonylurea [sic] had markedly reduced survival compared with both matched controls and those receiving metformin monotherapy. This supports the position of metformin as first‐line therapy and implies that metformin may confer benefit in non‐diabetes.”

What is the TAME Trial?

The Targeting Aging with Metformin (TAME) Trial is a placebo-controlled clinical trial designed to determine whether taking metformin delays the development or progression of age-related chronic diseases, including heart disease, cancer, and dementia. The study population will include 3,000 individuals at 14 sites across the U.S. who are between the ages of 65-79. Patients will receive either 1500mg Metformin daily or a placebo for up to 6 years. 

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1. Fluvoxamine as a potential treatment for COVID-19

Fluvoxamine Molecular Structure
*Since recording this podcast in January 2021, Steve Kirsch has publicly made misleading allegations regarding vaccine effectiveness and safety (e.g., Kirsch has claimed that mRNA vaccines are ineffective and are responsible for large numbers of deaths). While ExMedPod believes diverse viewpoints ought to be publicly discussed, we do not endorse Kirsch’s beliefs regarding vaccine safety and efficacy.*

[Update: August 2022 – A RCT published in the NEJM tested the efficacy of fluvoxamine and did not find a reduction in emergency department visits, hospitalizations, or deaths associated with Covid-19.]

Steve Kirsch | Fluvoxamine | Summary | Clinical Data

In this episode, Daniel Belkin and Mitch Belkin interview Steve Kirsch, the executive director of the COVID-19 Early Treatment Fund. We discuss why the antidepressant Fluvoxamine is being investigated as a potential treatment for COVID-19. We explore the observational and clinical data supporting its efficacy and examine the limitations of these studies. We briefly touch on why physicians and regulatory agencies have not embraced this medication despite some convincing real-world evidence on its clinical efficacy. 

Who is Steve Kirsch?

Steve Kirsch is a serial tech entrepreneur and philanthropist. He holds a Bachelor of Science and a Masters of Science in electrical engineering and computer science from MIT. He is currently the CEO of M10 and executive director of the COVID-19 early treatment fund.

What is Fluvoxamine?

Fluvoxamine (Luvox) is a Selective Serotonin Receptor Inhibitor (SSRI) that is clinically indicated for OCD in children, and can be used off label for depression. It was approved by the FDA in 1994 and has been used in millions of patients worldwide. Side effects include nausea, upset stomach (up to 25%), and other sexual side effects typical of SSRIs.

Summary

If you are looking for a quick summary of the evidence regarding Fluvoxamine, take a look at Steve Kirsch’s Powerpoint on Fluvoxamine.

Clinical Data:

Eric Lenze’s Phase 2 RCT on Fluvoxamine vs Placebo (Nov 2020) 

Results: “Of 152 patients who were randomized (mean [SD] age, 46 [13] years; 109 [72%] women), 115 (76%) completed the trial. Clinical deterioration occurred in 0 of 80 patients in the fluvoxamine group and in 6 of 72 patients in the placebo group (absolute difference, 8.7% [95% CI, 1.8%-16.4%] from survival analysis; log-rank P = .009). The fluvoxamine group had 1 serious adverse event and 11 other adverse events, whereas the placebo group had 6 serious adverse events and 12 other adverse events.”

David Seftel’s Open Label Clinical Trial of Fluvoxamine (Jan 2021)

Abstract: “We report a real-world experience using fluvoxamine for coronavirus disease 19 (COVID-19) in a prospective cohort in the setting of a mass outbreak. Overall, 65 persons opted to receive fluvoxamine 50mg twice daily and 48 declined. Incidence of hospitalization was 0% (0/65) with fluvoxamine and 12.5% (6/48) with observation alone. At 14 days, residual symptoms persisted in 0% (0/65) with fluvoxamine and 60% (29/48) with observation.”

Ongoing Phase 3 Clinical Trial on Fluvoxamine

An addendum from Steve: If you’d like to participate in the ongoing phase 3 study, check out www.stopcovidtrial.com. Enrollment is free and you can participate from the comfort of your own home.