Welcome back to What’s it Worth! Join your host, Dr. Diana Langworthy and returning co-host Dr. Meade Avery (2025 U of MN CoP Grad!!) as we PrEPare our clinical conclusions about a novel antiviral for HIV prevention. We also welcome an HIV expert, Dr. Daniel (Jude) Holt, who is a clinical pharmacist at North Memorial Health in the Infectious Diseases clinic. The study we critique compares twice yearly lenacapavir with daily emtricitabine/tenofovir alafenamide (F/TAF) or emtricitabine/tenofovir disoproxil fumarate (F/TDF) in cisgender women for HIV prevention (PrEP).

Key Points

1. HIV prevention is a critical step in the fight to end HIV
2. There are many barriers to compliance with daily oral HIV preventative medications including access and compliance
3. Twice yearly lenacapavir has been proven effective at preventing HIV in men who have sex with men and transgender women, but was yet to be studied in cisgender women
4. A twice yearly regimen can help patients overcome barriers to compliance
5. Will we find out "Where's "Wald"-o in our Stat Stop? ------> Tune in to find out!

References

1. [EPISODE TRIAL] Bekker LG, Das M, Abdool Karim Q, et al. Twice-Yearly Lenacapavir or Daily F/TAF for HIV Prevention in Cisgender Women. NEJM 2024;391(13):1179-1192.

2. Kelley CF, Acevedo-Quinones M, Agwu AL, et al. Twice yearly lenacapavir for HIV prevention in men and gender-diverse persons. NEJM 2024;392(13):1261-1276.

3. Bekerman E, Hansen D, Lu B, et al. Long-acting capsid inhibitor effective as PrEP against vaginal SHIV transmission in macaques. In: Proceedings and Abstracts of the 11th IAS Conference on HIV Science, July 18–21, 2021. Virtual: International AIDS Society, 2021. abstract.

4. Centers for Disease Control and Prevention. "HIV Prevention Research Synthesis Project." HIV Compendium of Best Practices. October 24, 2024, June 6, 2025, https://www.cdc.gov/hivpartners/php/hiv-treatment/index.htmlnters for Disease Control and Prevention

Contact Information

Podcast email: whatsitworthpodcast@gmail.com

Expert Guest

Dr. Daniel (Jude) Holt, PharmD, AAHIVP, CSP

Clinical Pharmacy Specialist - Infectious Disease

Specialty Pharmacy Infectious Disease Support

Daniel.Holt@northmemorial.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

Meade Avery, PharmD

2025 Graduate, University of Minnesota College of Pharmacy

Welcome back to What’s it Worth! Join your hosts, Dr. Diana Langworthy and Dr. Peyton Braun (PGY1 Pharmacy Resident), as we sift through strengths and limitations of at trial assessing the effects of empagliflozin on nonalcoholic fatty liver disease. The authors sought to quantify the impact of Sodium Glucose Cotransporter 2 - inhibitors (SGLT2i's) on Metabolic Dysfunction Associated Liver Disease (MASLD). This episode is full of EBP detective moments - dissecting trial language to get a clear picture of the story. Let's dive in and see what its worth!

Key Points

1. MASLD is a condition marked by an accumulation of fat in the liver which can lead to inflammation and irreversible liver damage
2. MASLD is often associated with conditions such as obesity, diabetes and hypertension
3. SGLT2i's are an evidence based therapy for the treatment of type II diabetes and have also shown to improve outcomes in heart failure and kidney disease
4. Extraglycemic benefits of this class of agents are of particular interest, with an increasing number of clinical trials investigating their potential impact on a variety of diseases (including MASLD)
5. Does a trial conducted with non-probability sampling have enough internal validity for empagliflozin in MASLD? ------> Tune in to find out!

References

1. [EPISODE TRIAL] Shojaei, F., Erfanifar, A., Kalbasi, S. et al. The effect of empagliflozin on non-alcoholic fatty liver disease-related parameters in patients with type 2 diabetes mellitus: a randomized controlled trial. BMC Endocr Disord 25, 52 (2025). https://doi.org/10.1186/s12902-025-01882-8

2. Zhang Y, Liu X, Zhang H, Wang X. Efficacy and safety of empagliflozin on nonalcoholic fatty liver disease: a systematic review and meta-analysis. Front Endocrinol 2022; doi: 10.3389/fendo.2022.836455

3. Rinella, Mary E.1; Neuschwander-Tetri, Brent A.2; Siddiqui, Mohammad Shadab3; Abdelmalek, Manal F.4; Caldwell, Stephen5; Barb, Diana6; Kleiner, David E.7; Loomba, Rohit8. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology 77(5):p 1797-1835, May 2023. | DOI: 10.1097/HEP.0000000000000323

4. Kanwal, Fasiha1,2,3; Neuschwander-Tetri, Brent A.4; Loomba, Rohit5; Rinella, Mary E.6. Metabolic dysfunction–associated steatotic liver disease: Update and impact of new nomenclature on the American Association for the Study of Liver Diseases practice guidance on nonalcoholic fatty liver disease. Hepatology 79(5):p 1212-1219, May 2024. | DOI: 10.1097/HEP.0000000000000670

5. Chen, Vincent L.1; Morgan, Timothy R.2,3; Rotman, Yaron4; Patton, Heather M.5,6; Cusi, Kenneth7; Kanwal, Fasiha8,9,10; Kim, W. Ray11. Resmetirom therapy for metabolic dysfunction-associated steatotic liver disease: October 2024 updates to AASLD Practice Guidance. Hepatology 81(1):p 312-320, January 2025. | DOI: 10.1097/HEP.0000000000001112
6. Stratton SJ. Purposeful Sampling: Advantages and Pitfalls. Prehospital and Disaster Medicine. 2024;39(2):121-122. doi:10.1017/S1049023X24000281

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

Peyton Braun, PGY1 Pharmacy Resident

University of Minnesota Medical Center - East Bank

Welcome back to What’s it Worth! Join your hosts, Dr. Diana Langworthy and Dr. Garrison Avery (PGY1 Pharmacy Resident), as we discuss the STOP ACEi trial comparing continuation of ACEi/ARB (angiotensin converting enzyme inhibitors/angiotensin receptor blockers) therapy in ESKD vs discontinuation of ACEi/ARB therapy. The authors sought to answer the question - Does discontinuation vs continuation of ACEi/ARB therapy slow the decline in eGFR once someone progresses to Stage 4/5 CKD. Let's get into the weeds of baseline characteristics - follow the episode's breadcrumbs to see if you can spot the key unmeasured confounders in this publication!

Key Points

1. ACEi/ARB therapy has demonstrated proven benefit in slowing the progression of CKD when initiated in Stages 1-3
2. Robust evidence is lacking to guide continuation vs discontinuation of ACEi/ARB therapy once a patient progresses to Stage 4/5 CKD
3. Compound symmetry covariance structures can be a useful statistical tool when the change between study visits in the key measurements is not anticipated to vary greatly (confused? So were we! Listen in for an explanation.)
4. What baseline characteristics might impact the primary outcome that may not have been accounted for? ------> Tune in to find out!

References

1. [EPISODE TRIAL] Bhandari S, Mehta S, Khwaja A, et al. Renin-Angiotensin System Inhibition in Advanced Chronic Kidney Disease. The STOP ACEi Trial. NEJM 2022;387:2021-2032.

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. Delgado C, Baweja M, Crews, D, et al. A Unifying Approach for GFR Estimation: Recommendations of the NKF-ASN Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease. JASN 2021;32(1@):2994-3015

4. Xie X, Liu Y, Perkovic V, et al. Renin-Angiotensin System Inhibitors and Kidney and Cardiovascular Outcomes in Patients with CKD: A Bayesian Network Meta-analysis of Randomized Clinical Trials. AJKD 2016;67(5):728-741.

5. DynaMed. Chronic Kidney Disease (CKD) in Adults. EBSCO Information Services. Accessed May 19, 2025. https://www-dynamed-com.ezp3.lib.umn.edu/condition/chronic-kidney-disease-ckd-in-adults-1

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, PGY1 Pharmacy Resident

University of Minnesota Medical Center - East Bank