Welcome to What’s it Worth! Join your host Dr. Diana Langworthy as we record live with our 2nd year Pharmacy Students for their EBP Pulse Check! We're exploring whether or not we should REDUCE our use of beta blockers in post MI patients who have a preserved ejection fraction by critiquing the REDUCE-AMI trial (NEJM 2024). Our expert guest for this episode is Dr. Anne Schullo-Feulner, Clinical Professor at the University of Minnesota College of Pharmacy and Cardiology Clinical Specialist at Methodist Hospital in St. Louis Park, MN. We discuss key concepts related to interpretation of results and how we can leverage our biostatistics knowledge to tackle Kaplan Meier Curves!

Special shout out to our PD2 Student Participants in the podcast: Andrew Gabbitas, Natalie Pearson, and Emma Maudal!

Key Points

1. The majority of evidence to support beta blocker use post-MI comes from the pre-reperfusion era
2. The REDUCE-AMI Trial aimed to determine whether or not patients with preserved ejection fraction after AMI should receive a beta blocker
3. Comparison of baseline characteristics from clinical trials to characteristics of your patient population is critical to determine generalizability of data to your practice
4. What are some hidden gems within these Kaplan Meier Curves? --> Tune in to find out!

References

1. [EPISODE TRIAL] Yndigegn T, Lindahl B, Mars K, et al. Beta-blockers after myocardial infarction and preserved ejection fraction. [REDUCE-AMI] NEJM 2024;390:1372-1381.
2. Virani SS, Newby K, Arnold SV, et al. 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Manatement of Patients with Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation 2023;148(9):e9-e119.
3. Lewis GD, Gosch K, Cohen LP. Effect of dapagliflozin on 6-minute walk distance in heart failure with preserved ejection fraction: PRESERVED-HF. Circ Heart Fail 2023;16(11):e010633.

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 Host Information

Dr. Anne Schullo-Feulner, PharmD, BCPS

Clinical Professor, University of Minnesota College of Pharmacy

Clinical Pharmacist - Cardiology, Methodist Hospital

Welcome to What’s it Worth! Join your host Dr. Diana Langworthy and guest host Rachel Cohen (PharmD Candidate, 2025) as we take a look at how cannabis affects pregnancy outcomes. Our guest, Dr. Ann Philbrick, PharmD, BCACP, will share her expertise with the current state of cannabis use and what it looks like to see patients who use cannabis in pregnancy.

Key Points

1. Existing evidence regarding cannabis in pregnancy has focused primarily on neonatal/fetal outcomes leaving a gap in maternal outcomes

2. Discussions about the safety of cannabis are more common as more states begin to legalize medical and recreational use

3. This is odd... Odds Ratio and Relative Risk can be similar but are not the same thing - when should we expect to see each of these?

4. Cannabis use in pregnancy was linked to increased maternal risk, however retrospective cohorts can present opportunity for unmeasured confounders---> TUNE IN to find out what those might be!

References

1. [EPISODE TRIAL] Young-Wolff KC, Adams SR, Alexeeff SE, et al. Prenatal Cannabis Use and Maternal Pregnancy Outcomes. JAMA Intern Med. Published online July 22, 2024. doi:10.1001/jamainternmed.2024.3270

2. Lo JO, Shaw B, Robalino S, et al. Cannabis Use in Pregnancy and Neonatal Outcomes: A Systematic Review and Meta-Analysis. Cannabis Cannabinoid Res. 2024;9(2):470-485. doi:10.1089/can.2022.0262

3. Baía I, Domingues RMSM. The Effects of Cannabis Use during Pregnancy on Low Birth Weight and Preterm Birth: A Systematic Review and Meta-analysis. Am J Perinatol. 2024;41(1):17-30. doi:10.1055/a-1911-3326

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 Host Information

Rachel Cohen, Student Pharmacist, Class of 2025 University of Minnesota

Guest Expert

Dr. Ann Philbrick, PharmD, BCACP, Associate Professor, University of Minnesota College of Pharmacy

Welcome back to What’s it Worth! Join your hosts, Dr. Diana Langworthy and P4 Garrison Avery, as we discuss the RENAL-AF trial comparing apixaban vs warfarin in hemodialysis patients. These authors aimed to assess safety and efficacy in one of the first prospective trials comparing DOACs with warfarin in hemodialysis patients. Ever read a trial that didn't enroll their goal number of patients? Let's dig into patient recruitment considerations in trials and also pragmatic applications to medication selection, and properties of drugs that can be cleared by hemodialysis with real pharmacokinetic data to support!

Key Points

1. The prevalence of atrial fibrillation in patients on hemodialysis has been noted to be as much as nine times higher than the general population
2. Warfarin presents a challenge as an anticoagulant in patients on hemodialysis due a heightened risk of bleeding and risk for vascular complications such as calciphylaxis
3. Studies that are published with neutral or negative findings can still provide important clinical context for understudied populations like patients on hemodialysis
4. What does this underpowered trial tell us? ------> Tune in to find out!

References

1. [EPISODE TRIAL] Pokorney SD, Chertow GM, Al-Khalidi HR, et al; RENAL-AF Investigators. Apixaban for Patients With Atrial Fibrillation on Hemodialysis: A Multicenter Randomized Controlled Trial. Circulation. 2022 Dec 6;146(23):1735-1745. doi: 10.1161/CIRCULATIONAHA.121.054990. Epub 2022 Nov 6. PMID: 36335914.

2. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2024 Apr;105(4S):S117-S314. doi: 10.1016/j.kint.2023.10.018. PMID: 38490803.

3. Joglar JA, Chung MK, Armbruster AL, et al. ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2024 Jan 2;149(1):e1-e156. doi: 10.1161/CIR.0000000000001193. Epub 2023 Nov 30. Erratum in: Circulation. 2024 Jan 2;149(1):e167. Erratum in: Circulation. 2024 Feb 27;149(9):e936. PMID: 38033089.

4. What's behind racial disparities in kidney disease? 2021. Harvard Health Publishing; Harvard Medical School. Accessed on March 10, 2024: https://www.health.harvard.edu/blog/whats-behind-racial-disparities-in-kidney-disease-2021020321842#:~:text=The%20most%20recent%20report%20from,per%20million%20for%20white%20Americans.
5. Mavrakanas TA, Samer CF, Nessim SJ, et al. Apixaban Pharmacokinetics at Steady State in Hemodialysis Patients. J Am Soc Nephrol. 2017 Jul;28(7):2241-2248. doi: 10.1681/ASN.2016090980. Epub 2017 Mar 16. PMID: 28302754; PMCID: PMC5491286.

6. Dialysis. National Kidney Foundation [Web]. 30 East 33rd Street, New York, NY 10016 © 2024 National Kidney Foundation Inc. Dialysis - Types, effectiveness, side effects | National Kidney Foundation

7. Vázquez, E., Vázquez-Sánchez, T. Sánchez-Perales, C. Letter by Vázquez et al Regarding Article, “Apixaban for Patients With Atrial Fibrillation on Hemodialysis: A Multicenter Randomized Controlled Trial” Circulation. 2023;148:378. DOI: 10.1161/CIRCULATIONAHA.122.063700 © 2023 American Heart Association, Inc.

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

Co-Host Information

Garrison (Griest) Avery, Student Pharmacist, Class of 2024

University of Minnesota College of Pharmacy

Welcome back to What’s it Worth! Join your hosts, Dr. Diana Langworthy and Garrison Avery, student PharmD, as we evaluate the 52 week reported outcomes of the ongoing Resmetirom Phase 3 trial. This trial is our first look at a medication currently seeking FDA approval to halt and reverse NASH and liver fibrosis. We also discuss Bonferroni statistical analysis, patients excluded from the trial, and bias in language.

Key Points

1. The FDA accelerated approval process might get your pharmacist-spidey senses going, but is it a concern?

2. Non-alcoholic steatohepatitis (NASH) is the most severe form of non-alcoholic fatty liver disease (NAFLD) and can progress to end stage liver disease if not managed properly

3. Recognizing when manuscript language may be suggestive of an effect (when one has not been statistically proven) is important to keep top of mind when critiquing an article.

4. Is there promise for patients with NAFLD to take their livers back in time? --> Tune in to find out!

References

1. [EPISODE TRIAL] Harrison SA, Bedossa P, Guy CD, et al; MAESTRO-NASH Investigators. A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis. N Engl J Med. 2024 Feb 8;390(6):497-509. doi: 10.1056/NEJMoa2309000. PMID: 38324483.
2. Kanwal F, Neuschwander-Tetri BA, Loomba R, Rinella ME. Metabolic dysfunction-associated steatotic liver disease: Update and impact of new nomenclature on the American Association for the Study of Liver Diseases practice fuidance on nonalcoholic fatty liver disease. Hepatology 2023;DOI: 10.1097/HEP.0000000000000670.
3. Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, et al. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease Hepatology 2023;77(5):1797-1835.
4. U.S. Food and Drug Administration. Accelerated Approval Program. Accessed March 8, 2024. https://www.fda.gov/drugs/nda-and-bla-approvals/accelerated-approval-program

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

Co-Host Information

Garrison (Griest) Avery, Student Pharmacist, Class of 2024

University of Minnesota College of Pharmacy

Did you miss us? We're back for Season 2 of What’s it Worth! Join your host, Dr. Diana Langworthy, and co-host Garrison (Griest) Avery (back at the end of his APPE year for some more EBP fun!), as they find out if phenobarbital is beating benzos in severe alcohol withdrawal! CI-WAt all the fuss is about in season two as we PAWSS and reflect on where single-site retrospective results and clinical takeaways can meet!

Key Points

1. Alcohol withdrawal syndrome is a complex process involving acute imbalances in excitatory and inhibitory neurotransmitters in the CNS that can predispose patients to potentially life threatening complications like seizure and alcohol withdrawal delirium.
2. Patients in vulnerable populations, like pregnant persons and imprisoned persons, represent a group that is often underrepresented in clinical trials - we discuss this from a retrospective and prospective angle.
3. The Poisson regression is used for analysis of count data while the Wilcoxan rank sum test is a nonparametric test that assumes unknown or not-normally distrubuted data.
4. Is phenobarbital back again for alcohol withdrawal syndrome? --> Tune in to find out!

References

1. [EPISODE TRIAL] D, Al-Hegelan M, Thompson J, Bronshteyn Y. Phenobarbital versus benzodiazepines in alcohol withdrawal syndrome. Neuropsychopharmacol Rep. 2023; 43: 532–541. https://doi.org/10.1002/npr2.12347
2. DiCenzo R. Clinical Pharmacist's Guide to Biostatistics and Literature Evaluation. ACCP. 2011. [Poisson and Wilcoxan information]
3. The ASAM Clinical Practice Guideline on Alcohol Withdrawal Management. American Society of Addiction Medicine, 2020. [Alcohol withdrawal management information, CIWA, PAWSS]
4. Weaver M, Jewell C, Tomlinson J. Phenobarbital for Treatment of Alcohol Withdrawal. Journal of Addictions Nursing 2009;20:1-5.

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

Co-Host Information

Garrison (Griest) Avery, Student Pharmacist, Class of 2024

University of Minnesota College of Pharmacy

Welcome to What’s it Worth - BONUS episode #2! Join your host Dr. Diana Langworthy and a come-back by P4 student co-host Marina Fahim as we get biosimilar! Our expert guest for this episode is Dr. Hannah Berg, Formulary Management Pharmacist at United Healthcare. We're discussing a trial that aimed to determine whether pegfilgrastim biosimilars were considered statistically equivalent to the pegfilgrastim originator product.  Biosimilars have the potential to offer cost-savings for patients requiring these expensive agents as they can introduce market competition and a potentially cheaper alternative to originator products.  

This bonus episode also coincides with a Journal Club assignment that students in my Evidence Based Practice course completed last week - Hello PHAR6782 Students! Great work on your first official Journal Clubs!

Key Points

1. Biologic agents are key in managing or preventing certain disease states, however often they present cost challenges to patients and healthcare systems
2. Febrile Neutropenia (FN) is a complication of high intensity chemotherapy regimens for patients with cancer
3. The NCCN guidelines recommend that patients at high risk receive a granulocyte colony stimulating factor (G-CSF) such as pegfilgrastim for the prevention of FN
4. Equivalence studies present an opportunity for pharmacists to critically evaluate historical data to determine clinical and statistical appropriateness of equivalence margins
5. How can you best interpret equivalence margins? ---> Tune in to find out!

References

1. [EPISODE TRIAL] Wang CY, Vouri SM, Park H, et al.  Comparative effectiveness of pegfilgrastim biosimilars vs originator for prevention of febrile neutropenia: A retrospective cohort study.  J Manag Care Spec Pharm. 2023;29(2):119-127.
2. Griffiths EA, Roy V, Bachiashvili K, et al.  Hematopoietic Growth Factors. NCCN Guidelines Version 1.2024. Accessed at https://www.nccn.org/professionals/physician_gls/pdf/growthfactors.pdf.
3. Casazza G, Solbiati M.  Can we trust equivalence and non-inferiority trials? Intern Emerg Med 2013;8:439-442.
4. Biosimilar Regulatory Review and Approval. US Food and Drug Administration Guidance Document. Accessed at https://www.fda.gov/media/151061/download.

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

Co-Host: Marina Fahim, P4 PharmD Student 2024, University of Minnesota

Expert Guest Information

Dr. Hannah Berg, PharmD

Formulary Management Pharmacist

UnitedHealthcare 

Welcome to What’s it Worth - a BONUS episode! Join your host Dr. Diana Langworthy and a come-back by P4 student co-host Garrison Griest as we get the scoop on poop! Our expert guest for this episode is Dr. Jen Ross, Antimicrobial Stewardship Clinical Pharmacist at M Health Fairview East and West Bank Hospitals. We're discussing a trial that evaluated the efficacy of a new orally administered fecal microbiota transplant capsule - SER-109. 

This episode coincides with a Journal Club assignment that students in my Evidence Based Practice course completed last week - Hello PHAR6782 Students! Great work on your first official Journal Clubs!

Key Points

1. C. Difficile infections are a public health concern and put a heavy burden on the health care system
2. Patients experiencing recurrent infections often are subject to expensive and/or prolonged antibiotic regimens with an option for site specific fecal microbiota transplant (FMT) at the discretion of their gastroenterologist
3. SER-109 (VOWST) is an orally administered FMT that is intended to be standardized for commercial development that demonstrated a reduction in recurrent C. Diff rates and early re-engraftment of a healthy microbiome
4. What populations are best to analyze for efficacy and safety in this Phase III RCT? ---> Tune in to find out!

Erratum: Garrison mention's that patients on prednisone 20mg/day or more were excluded - this was an exclusion criteria for the Rebyota(R) trial and NOT the SER-109 VOWST trial.

As it related to immunosuppressed patients, the SER-109 (VOWST) trial excluded: 

References

1. [EPISODE TRIAL] Feuerstadt P, Louie TJ, Lashner B, et al.  SER-109, an oral microbiome therapy for recurrent Clostridioides difficile infection. NEJM 2022;386:220-229.
2. Johnson S, Lavergne V, Skinner AM, et al.  Clinical practice guideline by the Infectious Disease Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused update guidelines on management of Clostridioides difficile infection in adults. CID 2021:doi.10.1093/cid/ciab549.
3. Khanna S, Assi M, Lee C, et al. Efficacy and Safety of RBX2660 in PUNCH CD3, a Phase III, Randomized, Double-Blind, Placebo-Controlled Trial with a Bayesian Primary Analysis for the Prevention of Recurrent Clostridioides difficile Infection. Drugs. 2022;82(15):1527-1538.
   doi:10.1007/s40265-022-01797-x
4. [Equity check reference] Argamany JR, Delgado A, Reveles KR. Clostridium difficile infection health disparities by race among hospitalized adults in the United States, 2001 to 2010. BMC Infect Dis 2016;16(1): 454.

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

Co-Host: Garrison Griest, P4 PharmD Student 2024, University of Minnesota

Expert Guest Information

Dr. Jennifer Ross, PharmD, BCIDP

Infectious Disease Clinical Pharmacist

East and West Bank Hospitals, M Health Fairview

Welcome to What’s it Worth! Join your host Dr. Diana Langworthy as we co-mingle with co-primary clues! Our expert guest for this episode is Dr. Natalie Heinrich, Medication Therapy Management Clinical Pharmacist in Neurology at M Health Fairview. We're discussing a trial evaluated the efficacy of zavegepant, a novel CGRP antagonist for nasal administration, for the treatment of acute migraine attack. Join us as we discuss the key points of co-primary outcomes, populations and power.

Key Points

1. Migraine disease affects 1 in 6 Americans and is a leading cause of disability
2. Triptan medications have been used for decades to treat migraine attacks, yet they have several contraindications due to vasoconstrictive effects
3. CGRP inhibitors are a new class of medications that target a specific peptide involved in migraine disease pathophysiology
4. Treatment for some disease states requires studies that involve two co-primary outcomes that are deemed equally important to determine true efficacy of an intervention
5. Does migraine disease fit the co-primary mold and is zavegepant ready for the migraine toolbox? --> Tune in to find out!

References

1. [EPISODE TRIAL] Lipton RB, Croop R, Stock DA, et al.  Safety, tolerability, and efficacy of zavegepant 10mg nasal spray for the acute treatment of migraine in the USA: a phase 3, double-blind, randomised, placebo-controlled multicentre trial. Lancet Neurol 2023;22(3):209-217.  
2.  Croop R, Madonia J, Stock DA, et al.  Zavegepant nasal spray for the acute treatment of migraine: a phase 2/3 double-blind, randomized, placebo-controlled, dose-ranging trial. Headache 2022;62:1153-1163.
3.  Product Information: Zavzpret(R), zavegepant 10mg/1 nasal spray. Pfizer Laboratories Div Pfizer Inc, New York, NY. 2023.
4. Ailani J, Burch RC, Robbins MS, et al.  The American Headache Society Consensus Statement: Update on integrating new migraine treatments into clinical practice. Headache 2021;61:1021-1039.
5. Burch R, Rizzoli P, Loder E.  The Prevalence and Impact of Migraine and Severe Headache in the United States: Figures and Trends from Government Health Studies. Headache 2018;58(4):496-505.

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

Expert Guest Information

Dr. Natalie Heinrich, PharmD

Medication Therapy Management Clinical Pharmacist, Neurology

Clinics and Surgery Center, M Health Fairview