What's it Worth? A Journal Club Podcast

Diana Langworthy
  • 5.0 (7)
  • Medicine
  • Updated Monthly

Get into the weeds with us as we take deep dives into clinical trials and build the essential skills of evidence critique! This podcast is a tool for healthcare professions students and practitioners to sharpen their science sleuth skills, learn key concepts about study design, biostatistics, and application of evidence to clinical practice.

  1. 2d ago

    S4E6 - Tylenol and Neurodevelopmental Disorders: Reassurance from a 2026 Systematic Review

    Welcome back to What's it Worth! Join your host, Dr. Diana Langworthy, and guests Dr. Alexis Quade and Dr. Tory Pressman, as they break down a 2026 systematic review and meta-analysis evaluating prenatal paracetamol exposure and child neurodevelopmental outcomes, including autism spectrum disorder, attention-deficit/hyperactivity disorder (ADHD), and intellectual disability. After renewed public attention in 2025 around Tylenol use in pregnancy and neurodevelopmental disorders, clinicians and patients are left asking how much weight to give observational medication safety signals. This episode explores how study design, confounding, outcome definitions, and risk-benefit thinking shape what we can — and cannot — conclude from the evidence. Let's dive in and see what it's worth! Key Points We explore why Tylenol, pregnancy, autism, ADHD, and neurodevelopmental disorders became such a high-profile medication safety conversation. The episode critiques a 2026 systematic review and meta-analysis, with a focus on study design choices like sibling comparisons, adjusted observational data, validated outcomes, and risk-of-bias assessment. We discuss why confounding by indication matters when the exposure is a medication used for fever, pain, or illness during pregnancy. We contrast the 2026 systematic review with the 2025 Navigation Guide paper and ask whether environmental health methods can be directly applied to pregnancy medication safety questions. Drs. Quade and Pressman help translate the evidence into real-world counseling about uncertainty, risk, benefit, and trust. When headlines move faster than evidence, how should clinicians and patients decide what's actually worth changing? ------> Tune in to find out! References [Episode Study] D'Antonio F, Flacco ME, Della Valle L, Prasad S, Manzoli L, Samara A, Khalil A. Prenatal paracetamol exposure and child neurodevelopment: a systematic review and meta-analysis. Lancet Obstet Gynaecol Womens Health. Published online January 16, 2026. doi:10.1016/S3050-5038(25)00211-0 Prada D, Ritz B, Bauer AZ, Baccarelli AA. Evaluation of the evidence on acetaminophen use and neurodevelopmental disorders using the Navigation Guide methodology. Environmental Health. 2025;24:56. doi:10.1186/s12940-025-01208-0 American College of Obstetricians and Gynecologists. Acetaminophen Use in Pregnancy and Neurodevelopmental Outcomes. Practice Advisory. Published September 22, 2025. Accessed April 13, 2026. Bérard A, Cottin J, Leal LF, et al. Systematic Review and Meta-Analysis: Acetaminophen Use During Pregnancy and the Risk of Neurodevelopmental Disorders in Childhood. J Am Acad Child Adolesc Psychiatry. 2026;65(4):484-504. Sheikh J, Allotey J, Khashan AS, et al. Maternal paracetamol (acetaminophen) use during pregnancy and risk of autism and attention deficit/hyperactivity disorder in offspring: umbrella review of systematic reviews. BMJ. 2025;391:e088141. Lee PC, Chen CY, Pan ML, et al. Maternal Acetaminophen Use and Child Neurodevelopment. JAMA Pediatr. Published online March 9, 2026. doi:10.1001/jamapediatrics.2026.0071.

    47 min

  2. May 27

    S4E5 - COBRRA Trial Breakdown: Bleeding Risk with Apixaban vs Rivaroxaban

    Welcome back to What's it Worth! Join your host, Dr. Diana Langworthy, and guest host Tim Haas, PharmD Candidate 2028, as they break down the COBRRA trial — a head-to-head comparison of apixaban vs. rivaroxaban for the treatment of acute venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE). For years, clinicians have debated whether one DOAC may carry a lower bleeding risk than another, despite both apixaban and rivaroxaban being widely used first-line therapies for acute VTE. Did the COBRRA trial finally give us a clearer answer? Let's dive in and see what it's worth! Key Points COBRRA was a randomized trial comparing apixaban vs. rivaroxaban in patients with acute symptomatic DVT and PE, with a primary focus on clinically relevant bleeding risk. The trial included a broad real-world VTE population, including patients with both provoked and unprovoked thromboembolism, pulmonary embolism, and deep vein thrombosis. We break down the Kaplan-Meier curve for clinically relevant bleeding and discuss what the timing of events may tell us about differences between these DOAC regimens. The study used a prospective randomized open-label blinded endpoint (PROBE) design, giving us an opportunity to discuss pragmatic trial methodology and real-world applicability. Which patients with acute VTE might benefit most from apixaban over rivaroxaban from a bleeding risk perspective? ------> Tune in to find out! References [Episode Trial] Castellucci LA, Chen VM, Kovacs MJ, et al. Bleeding Risk with Apixaban vs. Rivaroxaban in Acute Venous Thromboembolism. N Engl J Med. 2026;394(11):1051-1060. doi:10.1056/NEJMoa2510703 Stevens SM, Woller SC, Kreuziger LB, et al. Antithrombotic Therapy for VTE Disease: Second Update of the CHEST Guideline and Expert Panel Report. Chest. 2021;160(6):e545-e608. 2026 AHA/ACC/ACCP/ACEP/CHEST/SCAI/SHM/SIR/SVM/SVN Guideline for the Evaluation and Management of Acute Pulmonary Embolism. Circulation. 2026. doi:10.1161/CIR.0000000000001415. Ortel TL, Neumann I, Ageno W, et al. American Society of Hematology 2020 Guidelines for Management of Venous Thromboembolism: Treatment of Deep Vein Thrombosis and Pulmonary Embolism. Blood Adv. 2020;4(19):4693-4738. Agnelli G, Buller HR, Cohen A, et al. Oral Apixaban for the Treatment of Acute Venous Thromboembolism. N Engl J Med. 2013;369:799-808. The EINSTEIN Investigators. Oral Rivaroxaban for Symptomatic Venous Thromboembolism. N Engl J Med. 2010;363:2499-2510. Beyer-Westendorf J, Lensing AWA, Arya R, et al. Choosing wisely: the impact of patient selection on efficacy and safety outcomes in the EINSTEIN-DVT/PE and AMPLIFY trials. Thromb Res. 2017;149:29-37.

    47 min

  3. Apr 21

    S4E4 - Beyond Dopamine: Xanomeline-Trospium in Acute Schizophrenia

    Welcome back to What's it Worth! For over 70 years, the treatment of schizophrenia has been synonymous with dopamine D2 receptor blockade—until now. Join your host, Dr. Diana Langworthy, and guest Dr. Alexandra Rola (Psychiatry Clinical Pharmacist and Assistant Professor at Binghamton University) as they dive into the EMERGENT-3 trial. We're dissecting the efficacy and safety of xanomeline-trospium, a first-in-class muscarinic agonist that targets psychosis without the traditional side effects of dopamine antagonists. Is this the breakthrough psychiatry has been waiting for? Let's dive in and see what it's worth! Key Points Unlike traditional antipsychotics, xanomeline is a dual M1/M4-preferring muscarinic receptor agonist. By pairing it with trospium (a peripheral muscarinic antagonist), the "KarXT" combination aims to deliver CNS antipsychotic effects while minimizing peripheral side effects like nausea and vomiting. In this 5-week, Phase 3 trial of 256 adults with acute psychosis, xanomeline-trospium demonstrated a statistically significant and clinically meaningful 9.4-point greater reduction in the PANSS total score compared to placebo by week 5. The study showed significant improvements in both the Positive Syndrome Scale (hallucinations/delusions) and the Negative Syndrome Scale (social withdrawal/apathy), suggesting a more holistic impact on schizophrenia symptoms. While it avoids dopamine-related side effects, KarXT is associated with cholinergic-driven GI issues; nausea, dyspepsia, and vomiting were the most frequently reported adverse events. What are the ethics of a placebo controlled trial in acute psychosis when we have proven medications for treatment? Join us for an important conversation about equity and ethics in clinical trials. Can we treat psychosis without touching a single dopamine receptor? ------> Tune in to find out! References [EPISODE TRIAL] Kaul I, Sawchak S, Walling DP, et al. Efficacy and Safety of Xanomeline-Trospium Chloride in Schizophrenia: A Randomized Clinical Trial. JAMA Psychiatry. 2024;81(8):749-756. doi:10.1001/jamapsychiatry.2024.0785 World Medical Association. WMA Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Participants. Adopted by the 18th WMA General Assembly, Helsinki, Finland, June 1964, and amended by the 75th WMA General Assembly, Helsinki, Finland, October 2024. Waltz JA, Pujji SD, Colloca L. Placebo and nocebo phenomena in schizophrenia spectrum disorders: a narrative review on current knowledge and potential future directions. Psychol Med. 2025 Jul 18;55:e199. doi: 10.1017/S0033291725100901. Erratum in: Psychol Med. 2026 Feb 02;56:e37. doi: 10.1017/S0033291726103493.  Gara MA, Vega WA, Arndt S, et al. Influence of patient race and ethnicity on clinical assessment in patients with affective disorders. Arch Gen Psychiatry. 2012 Jun;69(6):593-600. doi: 10.1001/archgenpsychiatry.2011.2040.  Lawrence RE, Appelbaum PS. Ethics in placebo-controlled, acute treatment trials in schizophrenia: Two rival ethical frameworks. Schizophrenia Research 264 (2024) 372-377. Host Information Dr. Diana R. Langworthy, PharmD, BCPS Clinical Associate Professor, University of Minnesota College of Pharmacy Clinical Pharmacist - Inpatient Internal Medicine, M Health Fairview East Bank Hospital Guest Information Alexandra Rola, PharmD Clinical Assistant Professor, Pharmacy Practice, Binghamton University Psychiatry Clinical Pharmacist

    41 min

  4. Apr 2

    S4E3 - The GLP-1 Battle: Cardiovascular outcomes of Tirzepatide vs. Dulaglutide in the SURPASS-CVOT Trial

    Welcome back to What's it Worth! In this episode, your host Dr. Diana Langworthy is joined by Mia Lussier, PharmD, MS, Clinical Assistant Professor at Binghamton University and ambulatory care specialist, to dissect the results of the SURPASS-CVOT trial . As the first large-scale trial directly comparing a dual GLP-1/GIP agonist to a proven GLP-1 receptor agonist for cardiovascular outcomes, we ask: is tirzepatide officially the champion of metabolic and cardiovascular health? Join us for an evidence detective session as we evaluate the clinical worth of these findings Key Points SURPASS-CVOT was an active-comparator, double-blind trial that randomized 13,299 patients with Type 2 Diabetes and established ASCVD to receive either tirzepatide (up to 15 mg) or dulaglutide (1.5 mg) once weekly . Tirzepatide met its primary end point of noninferiority to dulaglutide for MACE (cardiovascular death, MI, or stroke) with a hazard ratio of 0.92. However, it did not achieve statistically significant superiority for this composite outcome (P=0.09) While CV outcomes were noninferior, tirzepatide showed superior metabolic benefits, including a -1.66 percentage point reduction in A1c (vs. -0.88 with dulaglutide) and an 11.6% reduction in total body weight (vs. 4.8% with dulaglutide). In a pre-specified secondary analysis of high-risk CKD patients, tirzepatide significantly slowed the decline of eGFR compared to dulaglutide, showing a difference of 3.17 ml/min/1.73m² over 36 months. Both agents had similar overall adverse event rates Was dulaglutide 1.5 mg weekly the best comparator vs tirzepatide for cardiovascular outcomes? ---> Tune in to find out! References [EPISODE TRIAL] Nicholls SJ, Pavo I, Bhatt DL, et al. Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes. N Engl J Med. 2025;393(24):2409-2420. doi: 10.1056/NEJMoa2505928. Gerstein H, Colhoun H, Dagenais G et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. The Lancet, 2019; 394, 121-130. Pratley RE, Aroda VR, Lingvay I, et al. SUSTAIN 7 investigators. Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial. Lancet Diabetes Endocrinol. 2018 Apr;6(4):275-286. doi: 10.1016/S2213-8587(18)30024-X. Epub 2018 Feb 1. PMID: 29397376. Marson SP, Bain SC, Consoli A, et al.  Semaglutide and cardiovascular outcomes in patients with Type 2 Diabetes. N Engl J Med 2016;375:1834-1844. Join the Conversation Subscribe to the What's it Worth? Podcast on Substack If you want to get new episode alerts, bonus content, and continue reflecting on what studies like this mean for real clinicians and real patients—head over to the What's it Worth? substack.  Have a study you'd like us to decode on a future episode? Email whatsitworthpodcast@gmail.com or share how you're navigating evidence in practice—I love hearing how clinicians and learners think through uncertainty. Host Information Dr. Diana R. Langworthy, PharmD, BCPS Clinical Associate Professor, University of Minnesota College of Pharmacy Clinical Pharmacist - Inpatient Internal Medicine, M Health Fairview East Bank Hospital Guest Information Mia Lussier, PharmD, MS Clinical Assistant Professor, Pharmacy Practice, Binghamton University Ambulatory Care Specialist

    44 min

  5. Mar 20

    S4E2 - The Kidney Formula Conundrum: Navigating eCrCl vs. eGFR in DOAC Dosing

    Welcome back to What's it Worth! Join your hosts, Dr. Diana Langworthy and guest Dr. Rachel Khan (Associate Professor at VCU School of Pharmacy), as they navigate the murky waters of renal function assessment in anticoagulant users. This episode dissects a critical insight from the ORBIT-AF II registry: the variability in DOAC (NOAC) dose eligibility when labs use newer kidney estimates . While clinical trials used Cockcroft-Gault (eCrCl), modern labs often report eGFR (MDRD or CKD-EPI), leading to a "renal identity crisis" for clinicians . We're putting on our EBP detective hats to explore why these formulas disagree—and what that means for your patients. Let's dive in and see what it's worth! Key Points The Gold Standard Gap: Landmark DOAC trials and product monographs almost exclusively use Cockcroft-Gault (eCrCl) for dosing, yet clinical labs have moved toward automated eGFR reporting . Formula Discordance: In the ORBIT-AF II cohort, agreement between eCrCl and eGFR was high overall (~93%), but declined in patients with established chronic kidney disease (CKD) . The "Misclassification" Mystery: Up to 42% of CKD patients could be classified for a different dose depending on which formula is used, with rivaroxaban showing the highest rates of variability . The Interpretive Challenge: While the study noted an association between formula-driven "undertreatment" and worse outcomes, we discuss the critical limitations—such as the lack of BSA-adjusted eGFR data—that make it difficult to conclude that eGFR is directly leading us to miss our target doses. Is your patient truly underdosed, or are we just using the wrong yardstick? ------> Tune in to find out! References [EPISODE TRIAL] Yao RJR, Holmes DN, Andrade JG, et al. Variability in Nonvitamin K Oral Anticoagulant Dose Eligibility and Adjustment According to Renal Formulae and Clinical Outcomes in Patients With Atrial Fibrillation With and Without Chronic Kidney Disease: Insights From ORBIT-AF II. J Am Heart As soc. 2023 Mar 21;12(6):e026605. doi: 10.1161/JAHA.122.026605.  St Peter WL, Bzowyckyj AS, Anderson-Haag T, et al; Moving forward from Cockcroft-Gault creatinine clearance to race-free estimated glomerular filtration rate to improve medication-related decision-making in adults across healthcare settings: A consensus of the National Kidney Foundation Workgroup for Implementation of Race-Free eGFR-Based Medication-Related Decisions. Am J Health Syst Pharm. 2025 Jun 11;82(12):644-659. Möller E, McIntosh JF, Van Slyke DD. STUDIES OF UREA EXCRETION. II: Relationship Between Urine Volume and the Rate of Urea Excretion by Normal Adults. J Clin Invest. 1928 Dec;6(3):427-65. doi: 10.1172/JCI100206. PMID: 16693839; PMCID: PMC434761. U.S. Food and Drug Administration (FDA). Pharmacokinetics in Patients with Impaired Renal Function — Study Design, Data Analysis, and Impact on Dosing and Labeling: Guidance for Industry. March 2024. Accessed December 2025.   Contact Information Podcast email: whatsitworthpodcast@gmail.com Host Information Dr. Diana R. Langworthy, PharmD, BCPS Clinical Associate Professor, University of Minnesota College of Pharmacy Clinical Pharmacist - Inpatient Internal Medicine, M Health Fairview East Bank Hospital Guest Information Dr. Rachel Khan, PharmD, BCPS Associate Professor, VCU School of Pharmacy Clinical Pharmacist - Internal Medicine, VCUHS

    52 min

  6. Feb 11

    S4E1 | Asking Better Questions of Evidence in 2026

    In this brief 2026 season opener, host Diana Langworthy, PharmD, BCPS pauses to acknowledge the weight of the moment—particularly here in Minnesota—where uncertainty, fear, and harm are being felt in very real ways across communities. This episode is not about policy analysis or debate. It's a reflection on what it means to hold space for thinking, teaching, and care when the world feels unstable—and why asking good questions, slowing down our reasoning, and practicing intellectual humility still matter in healthcare education and clinical practice. Diana also shares how What's It Worth? will move forward this season, and how the podcast, Substack (whatsitworthpodcast.substack.com), and future TikTok (Diana the Pharm.D.etective - @whatsitworthrx) content will work together as connected—but distinct—spaces for evidence critique, reflection, and public-facing curiosity.

    5 min

  7. 12/19/2025

    S3E14 | Defending Evidence in a Broken Trust Environment

    Welcome back What's it Worth? listeners. This episode steps away from traditional trial critique. It's a year-end reflection on what it means to practice evidence-based healthcare at a moment when trust in science, institutions, and clinicians is eroding—and when evidence itself is increasingly being misused to create fear rather than understanding. This episode is for frontline healthcare professionals and future providers who feel the weight of that shift and are asking how to respond without becoming part of a polarized conversation. The answer, I believe, is not louder certainty—but better questions. As we move into the next year, evidence-based practice will require more than knowing the literature. It will require clinicians who are willing to defend evidence with transparent communication, clarity, humility, and compassion—and who can help patients ask not just "Is there a study?" but "What's it worth?" Learn more and continue the conversation: Substack: https://whatsitworthpodcast.substack.com/ Email: whatsitworthpodcast@gmail.com

    8 min

  8. 12/16/2025

    S3E13 | Secondary SBP Prophylaxis — Asking Better Questions of Retrospective Data

    Episode Summary Secondary prophylaxis after spontaneous bacterial peritonitis (SBP) has long been considered standard of care—but how strong is the evidence behind it? In this episode, host Dr. Diana Langworthy is joined by Dr. Ben Webber (hospital medicine physician) and Danielle Luettel (PharmD Candidate 2026) to unpack a contemporary observational study examining outcomes associated with SBP prophylaxis. Together, they explore how historical trials, modern resistance patterns, and guideline recommendations intersect—and where uncertainty still remains. As care evolves over time, it is important to revisit standard practices to ensure they still make sense. How we revisit them is important and strong internal validity is still what we need to make practice changing claims.  Key Takeaways Secondary SBP prophylaxis is rooted in strong historical evidence but largely based on older trials. Contemporary observational data raise important questions about mortality benefit and patient selection. Guideline recommendations still support prophylaxis, but resistance patterns and evolving microbiology matter. Association does not equal causation—especially in retrospective database studies. Does this retrospective cohort study rise above the rest? ---> Tune in to find out! Featured Study Silvey S, Patel NR, Tsai, SY, et al. Higher Rate of Spontaneous Bacterial Peritonitis Recurrence With Secondary Spontaneous Bacterial Peritonitis Prophylaxis Compared With No Prophylaxis in 2 National Cirrhosis Cohorts. The American Journal of Gastroenterology 120(5):p 1066-1075, May 2025. | DOI: 10.14309/ajg.0000000000003075  Host Diana Langworthy, PharmD, BCPS Associate Professor, University of Minnesota College of Pharmacy Clinical Pharmacist, Inpatient Internal Medicine, M Health Fairview East Bank Hospital Guests Ben Webber, MD Associate Professor, Division of Hospital Medicine Senior Medical Director, Adult Med/Surg University of Minnesota Medical Center – East Bank Danielle Luetell PharmD Candidate, Class of 2026 Join the Conversation Subscribe to the What's it Worth? Podcast on Substack If you want to get new episode alerts, bonus content, and continue reflecting on what studies like this mean for real clinicians and real patients—head over to the What's it Worth? substack.  Have a study you'd like us to decode on a future episode? Email whatsitworthpodcast@gmail.com or share how you're navigating evidence in practice—I love hearing how clinicians and learners think through uncertainty. Additional References & Guidelines American Association for the Study of Liver Diseases (AASLD) Biggins, Scott W.*,1; Angeli, Paulo2; Garcia‐Tsao, Guadalupe3,4; et al. Diagnosis, Evaluation, and Management of Ascites, Spontaneous Bacterial Peritonitis and Hepatorenal Syndrome: 2021 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology 74(2):p 1014-1048, August 2021. | DOI: 10.1002/hep.31884 European Associate for the Study of the Liver EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis Journal of Hepatology, Volume 53, Issue 3, 397 - 417 Foundational Trial for Secondary Prophylaxis Ginés P, Rimola A, Planas R, et al. Norfloxacin prevents spontaneous bacterial peritonitis recurrence in cirrhosis: results of a double-blind, placebo-controlled trial. Hepatology. 1990 Oct;12(4 Pt 1):716–724. doi:10.1002/hep.1840120416. PMID:2210673.

    37 min
See All (36)

Ratings & Reviews

5
out of 5
7 Ratings

About

Get into the weeds with us as we take deep dives into clinical trials and build the essential skills of evidence critique! This podcast is a tool for healthcare professions students and practitioners to sharpen their science sleuth skills, learn key concepts about study design, biostatistics, and application of evidence to clinical practice.

Information