Heme Review – Details, episodes & analysis

Dr Pavlos Msaouel: https://faculty.mdanderson.org/profiles/pavlos_msaouel.html 0:00 Pretext and context MD Anderson Cancer Center 1:42 The Early Experiences That Shaped Dr Msaouel 3:39 The System of Cancer Research In the United States 5:25 FDA Drug Approvals and Special Designations For Oncology 11:09 A trade-off in our current system 12:35 Whoops 😞 I misspoke 14:35 Randomized trials are not supposed to be representative of a population 18:10 Inference for the treatment of Katie Coleman (metastatic oncocytoma) 25:12 It is much more valuable to refute hypotheses than to confirm them 28:05 All Models Are Wrong, But Some Are Useful 30:05 Recasting the Bias-Variance Trade-off as the Patient Relevance-Robustness Trade-off 33:38 High Relevance, Low Robustness: Subjective Bayes 34:46 High Robustness, Low Relevance: Pure Randomization 41:47 Signal To Noise Ratio 45:49 The Big Data Paradox 53:41 How the Big Data Paradox fits in with Katie Coleman's case 54:33 How the Big Data Paradox fits in with other branches of medicine 57:54 How do we rectify subjectivity in The Truth? 01:00:43 How do we address the problems introduced by the Big Data Paradox? 01:04:21 Duality in nature and a Twitter argument re: the Evidence-Based Deep Medicine Iceberg 01:07:03 Why the ideas coming from MD Anderson are coming from MD Anderson 01:09:39 Where you can find Dr Msaouel Dr Msaouel: https://twitter.com/PavlosMsaouel Heme Review: https://twitter.com/HemeReview

Produced by ⁠ @chubbyemu ⁠ Production Assistant: Nick Brown Secret channel:  @BigEmus  Cancer Patient Speaks With Her Oncologist ► https://youtu.be/Nddft_nc3Yc A Woman Had A Headache Lasting 3 Days (Katie's case) ► https://www.youtu.be/i9fLEvgZzRE References: Stephen Senn. Statistical Issues in Drug Development. Why representativeness should be avoided. https://academic.oup.com/ije/article/42/4/1012/656034 Commentary: Representativeness is usually not necessary and often should be avoided. https://academic.oup.com/ije/article/42/4/1018/658638 Impervious to Randomness: Confounding and Selection Biases in Randomized Clinical Trials. https://www.tandfonline.com/doi/full/10.1080/07357907.2021.1974030 A Causal Framework for Making Individualized Treatment Decisions in Oncology. https://www.mdpi.com/2072-6694/14/16/3923 Causal Diagram Techniques for Urologic Oncology Research. https://www.sciencedirect.com/science/article/pii/S1558767320301932 Causal inference and the data-fusion problem. https://www.pnas.org/doi/10.1073/pnas.1510507113 Causal Inference: What If. Miguel A Hernán and James M. Robins. https://www.hsph.harvard.edu/miguel-hernan/wp-content/uploads/sites/1268/2023/04/hernanrobins_WhatIf_31mar23.pdf There is Individualized Treatment. Why Not Individualized Inference? https://arxiv.org/abs/1510.08539 Unrepresentative big surveys significantly overestimated US vaccine uptake. https://www.nature.com/articles/s41586-021-04198-4 Unrepresentative Big Surveys Significantly Overestimate US Uptake https://arxiv.org/pdf/2106.05818.pdf Statistical Modeling: The Three Cultures. https://hdsr.mitpress.mit.edu/pub/uo4hjcx6/release/1 How “centaur AI” will radically reshape the future of healthcare. https://bigthink.com/health/how-centaur-ai-will-radically-reshape-the-future-of-healthcare/

Mug is here 😳 ► https://crowdmade.com/collections/chubbyemu

 @chubbyemu  energy drink video ► https://youtu.be/tAtaIZD0Ebs

A Student Ate Only Chips And Fries For 10 Years ► https://youtu.be/VINtwoyaF_8

A Mom Ate 5 Day Old Sushi 🍣 ► https://youtu.be/R0d6Dpx2li4

Vitamin B12 deficiency can cause neurologic problems. It's stored in the liver and isn't made in humans. It needs to be sourced via diet.

Video version of this podcast: https://youtu.be/oP_mJmWrfTQ

Chubbyemu video of this case: https://www.youtube.com/watch?v=WPxb2IG9MOk

Featuring: Dr Sonal Jagasia, MD, MPH. Psychiatrist in private practice.

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Dextromethorphan is an over the counter cough medicine. It is for coughs. Misuse of it can cause life threatening side effects.

References:

Dextromethorphan, chlorphenamine and serotonin toxicity: case report and systematic literature review. https://pubmed.ncbi.nlm.nih.gov/21175434/

Case of Serotonin Syndrome Initially Presenting as Diffuse Body Pain. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6196581/

Serotonin Syndrome. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865832

Bromism: An overlooked and elusive toxidrome from chronic dextromethorphan misuse. https://pubmed.ncbi.nlm.nih.gov/31864868/

Dextromethorphan-induced serotonin syndrome. https://pubmed.ncbi.nlm.nih.gov/19238739/

Cognitive Deterioration from Long-Term Misuse of Dextromethorphan:A Case Report. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1188627/

Pediatric Fatalities Associated With Over the Counter (Nonprescription) Cough and Cold Medications. https://pubmed.ncbi.nlm.nih.gov/19101060/

"DXM": a new drug of. https://pubmed.ncbi.nlm.nih.gov/9624331/

This episode is up to date as of 11 April 2021

Statement from water company CEO: https://www.youtube.com/watch?v=faCsru9Ctgk

Inside Edition video about this case: https://www.youtube.com/watch?v=lmEpmyc7g9Y

Local News talking about the water: https://www.youtube.com/watch?v=oGQJcnlk5ag

On March 13, the FDA was alerted to five cases of acute non-viral hepatitis (resulting in acute liver failure) in infants and children that occurred in November 2020 with an unknown cause reported to the Southern Nevada Health District. All five patients had been hospitalized but have since recovered. All patients were reported to have consumed “Real Water” brand alkaline water. These patients came from four different households. Five additional people, two adults and three children, from two of the four households were reported to have experienced other symptoms as well. Less severe symptoms included fever, vomiting, nausea, loss of appetite, and fatigue.

Chubbyemu video: https://www.youtube.com/watch?v=1MggKIfEld4

Heme Review video: https://www.youtube.com/watch?v=mPHXldh4_H4

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Chubbyemu YouTube channel: https://www.youtube.com/channel/UCKOvOaJv4GK-oDqx-sj7VVg

Heme Review YouTube channel: https://www.youtube.com/channel/UCNSoNc9s67nfOGlCXSu5VsA

References: 

Potential Benefits of Dietary Fibre Intervention in Inflammatory Bowel Disease https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4926452/

Effects of psyllium on glucose and serum lipid responses in men with type 2 diabetes and hypercholesterolemia https://academic.oup.com/ajcn/article/70/4/466/4729069

Anaphylaxis following psyllium ingestion https://pubmed.ncbi.nlm.nih.gov/6736485/

Long-term cholesterol-lowering effects of psyllium as an adjunct to diet therapy in the treatment of hypercholesterolemia https://academic.oup.com/ajcn/article/71/6/1433/4729388

Potential Benefits of Dietary Fibre Intervention in Inflammatory Bowel Disease https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4926452/ 

Effects of psyllium on glucose and serum lipid responses in men with type 2 diabetes and hypercholesterolemia https://academic.oup.com/ajcn/article/70/4/466/4729069 

Anaphylaxis following psyllium ingestion https://pubmed.ncbi.nlm.nih.gov/6736485/ 

Long-term cholesterol-lowering effects of psyllium as an adjunct to diet therapy in the treatment of hypercholesterolemia https://academic.oup.com/ajcn/article/71/6/1433/4729388 

Small Bowel Obstruction Secondary to a Metamucil Bezoar: Case Report and Review of the Literature https://pubmed.ncbi.nlm.nih.gov/29085697/

 The role of dietary fibre in the human colon https://pubmed.ncbi.nlm.nih.gov/6257366/ 

Intestinal obstruction caused by a laxative (Psyllium): A case report and review of the literature https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197948/

Video version of this interview: https://youtu.be/oLe9UdL-qIk

Jill's Blog: https://throughthevalley.ca

White Ribbon Project: https://twitter.com/TheWRP4LC

LUNGevity Foundation: https://lungevity.org

GO2 Foundation: https://go2foundation.org

Lung Cancer Canada: https://www.lungcancercanada.ca

Lung Foundation Australia: https://lungfoundation.com.au

Lung Cancer Europe (LUCe): https://www.lungcancereurope.eu

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Please note the CONTENT WARNING at the beginning-- there's a reason I can't make the videos as described in this episode. They may surface in a different form at some time in the future.

Heme Review YouTube: https://www.youtube.com/channel/UCNSoNc9s67nfOGlCXSu5VsA

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Video of this interview: https://youtu.be/o15HCjtSkug

Chubbyemu video https://youtu.be/ChPeG19qKUo

Christopher's recount of his case: https://youtu.be/7BpymtR2vpA

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2,4-Dinitrophenol (DNP) is a chemical that is not approved for weight loss. It is a classic case of efficacy, but without safety in the setting of weight loss. This setting of weight loss can be prone to chemical misuse, further exacerbating understanding in human systems. Christopher is one of 2 - 3 cases documented in literature to have survived an accident with DNP for weight loss. As of 2021, one organization has permission from the US FDA to investigate DNP in some neurodegenerative disorders. These are rare diseases with limited standards of care, therefore extenuating circumstances to find anything that could potentially improve patient outcomes.

References:

Role of dantrolene in dinitrophenol (DNP) : A continuing question? Am J Emerg Med. 2019 Jun;37(6):1216.e1-1216.e2. https://pubmed.ncbi.nlm.nih.gov/30948257/

2,4-dinitrophenol (DNP): a weight loss agent with significant acute toxicity . J Med Toxicol. 2011 Sep;7(3):205-12. https://pubmed.ncbi.nlm.nih.gov/21739343/

Ambient temperature and mortality from unintentional . JAMA. 1998 Jun 10;279(22):1795-800. https://pubmed.ncbi.nlm.nih.gov/9628710/

Beware the yellow slimming pill: fatal 2,4-dinitrophenol. BMJ Case Rep. 2016 Apr 4;2016. https://pubmed.ncbi.nlm.nih.gov/27045052/

Dantrolene is not the answer to 2,4-dinitrophenol poisoning: more heated debate. BMJ Case Rep. 2018 Dec 19;11(1):e225323. https://pubmed.ncbi.nlm.nih.gov/30573533/

The effect of 2,4-dinitrophenol on adipose-tissue metabolism. Biochem J. 1969 Feb;111(4):431-44. https://pubmed.ncbi.nlm.nih.gov/4388239/

The mechanism of uncoupling of oxidative phosphorylation by 2,4-dinitrophenol. J Biol Chem. 1967 Oct 25;242(20):4577-83. https://pubmed.ncbi.nlm.nih.gov/4964808/

MECHANISMS OF DINITROPHENOL TOXICITY. Simon E.W. Biological Reviews. Vol 28. (4). Nov 1953.

Identification and Importance of Brown Adipose Tissue in Adult Humans. https://www.nejm.org/doi/full/10.1056/NEJMoa0810780

Mitochondrial uncoupling as a target for drug development for the treatment of obesity. Obes Rev. 2001 Nov;2(4):255-65. https://pubmed.ncbi.nlm.nih.gov/12119996/

LC-MS-MS analysis of 2,4-dinitrophenol and its phase I and II metabolites. J Ana Toxicol. Jan-Feb 2007;31(1):55-61. https://pubmed.ncbi.nlm.nih.gov/17389084/

Uncouplers of oxidative phosphorylation. Environ Health Perspect. 1990 Jul;87:213-8. https://pubmed.ncbi.nlm.nih.gov/2176586/

Texas Woman Charged with Selling Misbranded

https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/press-releases/texas-woman-charged-selling-misbranded-drug

Patient CE's personal recount of case: https://youtu.be/7BpymtR2vpA

Patient CE's  Interview: https://youtu.be/o15HCjtSkug

Chubbyemu video on this case: https://youtu.be/ChPeG19qKUo

Heme Review video version: https://youtu.be/jgDUMNaVqHg

2,4-Dinitrophenol (DNP) is a chemical that is not approved for weight loss in the United States. It is a classic case of efficacy, but without safety in the setting of weight loss. This setting of weight loss can be prone to chemical misuse, further exacerbating understanding in human systems. Christopher is one of 2 - 3 cases documented in literature to have survived an accident with DNP for weight loss. As of 2021, one organization has permission from the US FDA to investigate DNP in some neurodegenerative disorders. These are rare diseases with limited standards of care, therefore extenuating circumstances to find anything that could potentially improve patient outcomes.

Tweet me: https://www.twitter.com/hemereview

IG me: https://www.instagram.com/hemereview

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References:

Role of dantrolene in dinitrophenol (DNP) : A continuing question? Am J Emerg Med. 2019 Jun;37(6):1216.e1-1216.e2. https://pubmed.ncbi.nlm.nih.gov/30948257/

2,4-dinitrophenol (DNP): a weight loss agent with significant acute toxicity . J Med Toxicol. 2011 Sep;7(3):205-12. https://pubmed.ncbi.nlm.nih.gov/21739343/

Ambient temperature and mortality from unintentional . JAMA. 1998 Jun 10;279(22):1795-800. https://pubmed.ncbi.nlm.nih.gov/9628710/

Dinitrophenol as a Medicine. Cells. 2019 Mar; 8(3): 280. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468406/

The Interaction of Highly Active Uncouplers With Mitochondria. Biochimica et Biophysica Acta, 639 (1981) 225-242.

Beware the yellow slimming pill: fatal 2,4-dinitrophenol. BMJ Case Rep. 2016 Apr 4;2016. https://pubmed.ncbi.nlm.nih.gov/27045052/

Dantrolene is not the answer to 2,4-dinitrophenol poisoning: more heated debate. BMJ Case Rep. 2018 Dec 19;11(1):e225323. https://pubmed.ncbi.nlm.nih.gov/30573533/

The effect of 2,4-dinitrophenol on adipose-tissue metabolism. Biochem J. 1969 Feb;111(4):431-44. https://pubmed.ncbi.nlm.nih.gov/4388239/

The mechanism of uncoupling of oxidative phosphorylation by 2,4-dinitrophenol. J Biol Chem. 1967 Oct 25;242(20):4577-83. https://pubmed.ncbi.nlm.nih.gov/4964808/

MECHANISMS OF DINITROPHENOL TOXICITY. Simon E.W. Biological Reviews. Vol 28. (4). Nov 1953.

Identification and Importance of Brown Adipose Tissue in Adult Humans. https://www.nejm.org/doi/full/10.1056/NEJMoa0810780

Mitochondrial uncoupling as a target for drug development for the treatment of obesity. Obes Rev. 2001 Nov;2(4):255-65. https://pubmed.ncbi.nlm.nih.gov/12119996/

LC-MS-MS analysis of 2,4-dinitrophenol and its phase I and II metabolites. J Ana Toxicol. Jan-Feb 2007;31(1):55-61. https://pubmed.ncbi.nlm.nih.gov/17389084/

Uncouplers of oxidative phosphorylation. Environ Health Perspect. 1990 Jul;87:213-8. https://pubmed.ncbi.nlm.nih.gov/2176586/

Texas Woman Charged with Selling Misbranded

https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/press-releases/texas-woman-charged-selling-misbranded-drug

Based on N Engl J Med 2020; 383:1263-1275. https://www.nejm.org/doi/full/10.1056/NEJMcpc2002420

Chubbyemu video of this case: https://open.spotify.com/episode/77z8mZGbmBI4E2JtA8GXsh?si=k_qV_IkrQiqTGpn8EXK61Q

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Licorice candy has glycyrrhizin which increases cortisol (stress hormone) levels in the body. This causes hypokalemia. Hypo- low. Kal- kalium (potassium). emia- presence in blood. Potassium signals muscle relaxation. Low potassium, low relaxation. Heart can't relax, then it stops.  Real licorice candy is not easy to get in the United States. It's not at big chain grocery stores. Most of what you can buy from the big brands is licorice flavored, and won't do this.

References:

A 54-Year-Old Man with Sudden Cardiac Arrest. N Engl J Med 2020; 383:1263-1275. https://www.nejm.org/doi/full/10.1056/NEJMcpc2002420

The Pharmacological Activities of Glycyrrhizinic Acid (“Glycyrrhizin”) and Glycyrrhetinic Acid. Sweeteners. 2018 : 245–261. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123798/

Sustained Leukocyte Count during Rising Cortisol Level. Acta Haematologica 118(2):73-6. https://www.researchgate.net/publication/6298458

https://www.nobelprize.org/prizes/medicine/1964/bloch/lecture/

Licorice-Induced Hypermineralocorticoidism. N Engl J Med 1991; 325:1223-1227. https://www.nejm.org/doi/full/10.1056/NEJM199110243251706

Young WF, et. al. Apparent mineralocorticoid excess syndromes (including chronic licorice ingestion). In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2019.

Quinkler M, Stewart PM. Hypertension and the cortisol-cortisone shuttle. J Clin Endocrinol Metab 2003; 88:2384.

Funder JW. Apparent mineralocorticoid excess. J Steroid Biochem Mol Biol 2017; 165:151.

Funder JW. 11 beta-Hydroxysteroid dehydrogenase: new answers, new questions. Eur J Endocrinol 1996; 134:267.