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Discoveries & Impact (May 2023)

May 11, 2023
by Melanie Ho, Shin Mei Chan and Sarah L. Spaulding

Discoveries & Impact highlights select scientific discoveries across the Department of Internal Medicine...

Yale Researchers Assess Impact of Risk Alert on Heart Failure Patients

Although the number of patients with heart failure (HF) admitted to the intensive care unit (ICU) is increasing, there is limited data on patient outcomes for this population. In particular, the role of risk prediction tools in improving outcomes is not well-understood or characterized. A team of Yale researchers sought to assess this impact.

Using the REVeAL-HF (Risk Evaluation and its Impact on Clinical Decision Making and Outcomes in Heart Failure) trial, researchers conducted a post hoc analysis of the impact of an electronic health record alert of a patient’s one-year mortality risk. The analysis determined that risk scores alone did not reduce mortality, rehospitalization, and length of stay in this population, underscoring the challenges faced in risk stratification for HF patients requiring critical care.

Read more in “Risk Prediction for Heart Failure Patients Admitted to the Intensive Care Unit.”

O'Connor KD, Yamamoto Y, Sen S, Samsky MD, Wilson FP, Desai N, Ahmad T, Fuery MA. Risk Prediction for Heart Failure Patients Admitted to the Intensive Care Unit: Insights From REVeAL-HF. JACC Heart Fail. 2023 Apr 12:S2213-1779(23)00076-8. doi: 10.1016/j.jchf.2023.01.021. Epub ahead of print. PMID: 37052546.

Building Trust in the FDA’s Accelerated Approval Program

The Food and Drug Administration’s (FDA) accelerated approval program allows for a quicker approval of drugs for conditions that are serious and have no adequate treatment options. Accelerated approval is based on significant improvement in a surrogate endpoint but requires additional trials to fully demonstrate their clinical benefits. Recently, the FDA granted accelerated approval for drugs treating Duchenne’s muscular dystrophy and Alzheimer’s disease. In a new article, Yale researchers recognize the challenges faced by patients, caregivers, and physicians in managing residual uncertainty around the safety and efficacy of these drugs and suggest ways to foster trust and transparency in the FDA.

The authors propose that the FDA consider whether the accelerated approval pathway is necessary for common diseases that have measurable health effects within a short period where it may be possible to conduct large, high-quality trials before opting for expedited approval. Secondly, the agency may want to institute standardized reevaluation periods for all surrogate endpoints to ensure that scientific evidence continues to support their use. Finally, the FDA may need to provide informational materials to communicate any remaining doubt at the time of approval. Learn more in “Ensuring Public Trust in an Empowered FDA.”

Ross JS, Berg KM, Ramachandran R. Ensuring Public Trust in an Empowered FDA. N Engl J Med. 2023 Apr 6;388(14):1249-1251. doi: 10.1056/NEJMp2300438. Epub 2023 Apr 1. PMID: 37017494.

Older Adults with Dementia & Their Adult Children Cope with COVID-19 Together

During the COVID-19 pandemic, many Americans cared for a parent with cognitive impairment while navigating pandemic-related challenges—such as financial hardship, increased childcare responsibilities, and decreased social interaction. In a new qualitative study, Yale researchers examine conversations between individuals with early-stage dementia and their adult children to understand the socio-emotional impacts of the pandemic and interpersonal support strategies.

Forty-three pairs consisting of a person with dementia and their adult child engaged in conversation. Participants often expressed anxiety about prolonged reduction of social engagement or a fear of contracting the coronavirus. Parents and their children coped by making meaning of their situations, which included finding positive aspects of the pandemic, and spending more quality time together. While adult children described ways they provided assistance with the tangible needs of their parents, their parents reciprocated with emotional support. Read more in “Navigating the COVID-19 pandemic together: Discussions between persons with early-stage dementia and their adult children.”

Ali T, Mroz EL, Valeika S, Mendez EN, Cohen AB, Monin JK. Navigating the COVID-19 pandemic together: Discussions between persons with early-stage dementia and their adult children. Int J Geriatr Psychiatry. 2023 Mar;38(3):e5905. doi: 10.1002/gps.5905. PMID: 36929513.

Health Literacy Imperative in Young Patients with Sickle Cell Disease

A new study sheds new light on the association between cognitive ability and health literacy in patients with sickle cell disease. Sickle cell disease can lead to many health complications, including strokes, which can impact cognitive function.

For pediatric and young adult patients with sickle cell disease, these neurologic deficits may play a hindering role in patient wellness and access to care. This study, a cross-sectional analysis, assessed 93 patients from two sites. The team demonstrated that only 43 percent of participants had adequate health literacy, measured by the Newest Vital Sign tool. Lower inadequate health literacy was associated with lower abbreviated full-scale intelligence quotient, a measure of IQ and younger age. Health literacy is particularly important as adolescent patients navigate the ability to understand and use information to make informed decisions for themselves. The authors suggest that among young patients with sickle cell disease, there must be robust routine screening for neurocognitive deficits in order to optimize patient care.

To learn more about this study, read “Health literacy correlates with abbreviated full-scale IQ in adolescent and young adults with sickle cell disease.”

Bhatt N, Calhoun C, Longoria J, Nwosu C, Howell KE, Varughese T, Kang G, Jacola LM, Hankins JS, King A. Health literacy correlates with abbreviated full-scale IQ in adolescent and young adults with sickle cell disease. Pediatr Blood Cancer. 2023 May;70(5):e30281. doi: 10.1002/pbc.30281. Epub 2023 Mar 2. PMID: 36861391.

Optimizing Treatment with Multidrug-resistant HIV Infection: a Role for Lenacapavir?

A new review by Jessica Tuan, MD, MS, and Onyema Ogbuagu, MBBCh, discusses the role of lenacapavir, a novel HIV-1 capsid inhibitor recently granted breakthrough therapy designation by the U.S. Food and Drug Administration in 2019 for the treatment of HIV.

The review, published in Expert Review of Anti-infective Therapy, discusses the chemistry, mechanism of action, pharmacokinetics, and pharmacodynamic profile of the promising compound. The authors further discuss the safety and efficacy as demonstrated in clinical trials, specifically the phase 3 CAPELLA trial, for which Ogbuagu serves as primary investigator, and provide expert opinion on its range of applications. Based on current evidence, Tuan and Ogbuagu suggest that lenacapavir may be used in conjunction with one or two additional fully active drugs and may be specifically useful in those with multidrug-resistant HIV infection and limited treatment options remaining.

To learn more, read the article “Lenacapavir: a twice-yearly treatment for adults with multidrug-resistant HIV infection and limited treatment options.”

Tuan J, Ogbuagu O. Lenacapavir: a twice-yearly treatment for adults with multidrug-resistant HIV infection and limited treatment options. Expert Rev Anti Infect Ther. 2023 Apr 20:1-6. doi: 10.1080/14787210.2023.2203913. Epub ahead of print. PMID: 37067160.

New Review Assesses Magnesium Disorders

A recent review published in Mayo Clinic Proceedings, led by Mark Perazella, MD, professor of medicine (nephrology), outlines the most up-to-date knowledge on disorders resulting in hypomagnesemia, or magnesium deficiency. The authors conducted a review of literature via the online archive PubMed, ranging from 1970 to 2022, synthesizing information into a scoping review.

In this article, the team reviews common clinical manifestations, magnesium handling in the kidneys, drug-associated magnesium disorders, laboratory diagnostic testing, and treatment paradigms. Additionally, given a lack of consensus regarding the optimal treatment paradigm for hypomagnesemia, expert opinion is provided based on the clinical expertise of the author team.

To read this article, visit Acquired Disorders of Hypomagnesemia.

Rosner MH, Ha N, Palmer BF, Perazella MA. Acquired Disorders of Hypomagnesemia. Mayo Clin Proc. 2023 Apr;98(4):581-596. doi: 10.1016/j.mayocp.2022.12.002. Epub 2023 Mar 3. PMID: 36872194.

Lupus-Associated Vasculitis Treated with Vascular-Targeted Therapy

Systemic lupus erythematosus (SLE), an autoimmune disease, is associated with a number of skin-related complications, including cutaneous vasculitis (inflamed blood vessels at the skin). Yale rheumatologists and dermatologists partnered on a case published in JAMA Dermatology which reported on the successful use of vascular-targeted agents to treat SLE-associated vasculitis affecting the hands and feet.

Physicians treated a female patient in her 40s with a diagnosis of SLE and a one-year history of tender papules, plaques, and ulcers on her hands and feet who had been previously treated with topical and intralesional corticosteroids and nifedipine-verapamil without clinical effect. The patient was treated with a regimen of aspirin daily and pentoxifylline and sildenafil, both three times daily, as well as onabotulinumtoxinA injections.

Two weeks after receiving injections, the patient experienced significant improvement in hand function and pain. At four weeks, the patient’s hand ulcers were completely healed, and at 10 weeks, the patient’s toe ulcers had healed. Maintained on vasodilator/antiplatelet therapy, the patient’s lesions have remained healed. This work highlights the importance of a vascular-focused approach in treating SLE-associated vasculitis.

Read more in “Vascular-Targeted Therapy for Systemic Lupus Erythematosus–Associated Vasculitis.”

Xu S, Patrignelli RJ, Ramachandran S, Koumpouras F, Desir D, Ko CJ, Gehlhausen JR. Vascular-Targeted Therapy for Systemic Lupus Erythematosus-Associated Vasculitis. JAMA Dermatol. 2023 Apr 1;159(4):460-462. doi: 10.1001/jamadermatol.2023.0077. PMID: 36884229.

Submitted by Julie Parry on May 11, 2023