Digest 58: RSV vaccine roulette, the MSK syndrome of menopause, transfusion thresholds, and to continue or not continue the beta blocker

October 18, 2024 | By Nora Taranto

Welcome Back to The Curbsiders Digest!

In this issue, we discuss RSV vaccine roulette, the MSK syndrome of menopause, transfusion thresholds, and to continue or not continue the beta blocker. Effortlessly absorb important medical news, with our twice monthly newsletter featuring easily digestible analysis of the latest practice-changing articles, and of course…bad puns. 

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Issue 58

10/18/2024

Appetizers (to whet your appetite) 

Palate Cleanser (aka the melon part of the meal) 

The Main Course

A Digestif or two

Appetizers

Brought to you hot off the stove, from a variety of specialties. Delivered in super tasty, bite-sized morsels. 
-Jennifer DeSalvo MD; Beth Garbitelli MD; Hannah Smith MD 

• Understanding MSK impacts of Menopause. A new review article in Climacteric aims to describe and discuss the musculoskeletal syndrome of menopause – a constellation of symptoms including muscle pain, arthralgia, muscle mass loss, declining bone density, tendon changes, ligament injury, adhesive capsulitis, and osteoarthritis progression that occurs during or after menopause. While estrogen’s impact on bone density is well-known, the authors highlight the role of inflammation and cite multiple possible cellular pathways by which estrogen changes might be contributory to muscular/bony pain and sarcopenia during the menopausal period. (BG)
• Headache Med Head-to-Head. Migraines cause debilitating symptoms, often leaving both patients and providers grasping for the right treatment. A review and meta-analysis in BMJ assessed 137 double-blind RCTs from 1991 through 2023 to identify which oral medicine has the best efficacy. Eletriptan, rizatriptan, sumatriptan, and zolmitriptan (in that order) were the most effective for immediate (2-hour) pain relief, with eletriptan and ibuprofen reigning superior for 24-hour pain relief. Cardiovascular side effects limit the use of triptans. NSAIDs performed equal to the newer gepant drug class (rimegepant, ubrogepant), and paracetamol was largely limited in its pain relief, but well-tolerated. The analysis was limited by moderate heterogeneity. (BG)
• Exploring different transfusion TRAIN(s) of thought. The multi-center, open-label Transfusion Strategies in Acute Brain Injured Patients (TRAIN) trial just published in JAMA randomized 850 patients in the intensive care unit with acute brain injury and anemia to a liberal (hemoglobin (Hgb) ˂9 g/dL) or restrictive (Hgb ˂7 g/dL) transfusion strategy over 28 days. Those in the liberal arm had significantly fewer unfavorable neurologic outcomes compared to those in the restrictive arm (62.6% vs.72.6%, aRR 0.86, 95% CI 0.79-0.94), with decreased frequency of cerebral ischemic events in the liberal versus restrictive strategy groups (8.8% vs 13.5%). Meanwhile, a secondary analysis of the MINT trial (which identified a trend towards lower rates of recurrent MI/death with a liberal transfusion strategy in patients with acute MI and Hgb < 10) emulated various transfusion thresholds and found a generally increasing risk of MI/death with lower Hgb thresholds for transfusion, but no significantly different adverse outcomes with a threshold of Hgb <9 vs <10 g/dL–suggesting that a liberal transfusion threshold of <9 g/dL may be adequate and avoid transfusion-related adverse effects. (JD) 
• To continue beta-blockers long-term after MI or not? A multicenter, open-label, non-inferiority trial just published in NEJM randomized 3698 patients with a history of myocardial infarction (MI) and left ventricular ejection fraction ≥40% without a cardiovascular event in the preceding six months to interruption or continuation of beta-blocker therapy. The primary endpoint included a composite of death, nonfatal MI, nonfatal stroke, or cardiovascular-related hospitalization at minimum 1 year follow-up. Over a median follow-up of 3 years, interruption of long-term beta-blocker treatment was not found to be noninferior to continuation, with the primary outcome occurring in 23.8% of patients in the interruption group and 21.1% of patients in the continuation group (HR 1.16, 95% CI 1.01 – 1.33, p=0.44 for non-inferiority). Beta-blocker interruption did not improve patients’ quality of life. (JD) 
• IVIG in viral infections for the immunocompromised? In a retrospective cohort study recently published in the Annals of Allergy, Asthma, and Immunology, researchers reviewed all immunocompromised patient admissions for respiratory viral infections over 5 years at two Johns Hopkins sites. Of the 270 admissions evaluated, 74% were transplant patients, and 36% received IVIG. Use of IVIG was associated with shorter ICU length of stay by an average 0.5 fewer days but a slightly longer hospital length of stay; IVIG administered within 48 hours of hospitalization was associated with shorter ICU length of stay by ~2 days and a shorter overall hospital stay for patients admitted at least 2 days. There were no significant differences in readmission rates or rates of death. (HS)  

Palate Cleanser

The melon part. To get rid of the taste of those pesky apps.  And to fill your brain with some fun facts.

“So visibly a mother” is not positive feedback frequently heard from others in medicine.  In a “Piece of my Mind” article in JAMA, Dr. Emily Pinto Taylor beautifully highlights the importance of discussing and modeling work-life integration for trainees and early-career faculty. For example, she allows “No” to be a complete sentence, avoids scheduling meetings and working from 5-7 PM so she can be present with her children after school and before bed, finds shift switches or starts rounds late to attend children’s school activities when able, and partners with parent-friends to share photos and videos of her children when she’s not able to attend activities. Additionally, she stresses the need to “model for others the flexibility that we desire for ourselves,” empowering medical trainees to take time for parental leave, utilize breaks during the workday to pump breast milk if desired, or leave to care for a sick pet or child. Check out her article for more pearls on how she prioritizes parenthood as her “most enduring legacy.”

– Jennifer DeSalvo MD

The Main Course

Molly Heublein MD 

RSV Vaccines–The New Kid on the (Vaccine) Block 
Just in time for cold season, we’re pivoting from pneumococcal vaccination in last month’s Digest (#57) to the RSV vaccine(s) this issue–another rapidly evolving area that can be hard to follow.  

RSV (Respiratory Syncytial Virus) is a single-stranded RNA virus that causes common seasonal infections ranging from no or mild cold symptoms to severe lower respiratory tract infections leading to hospitalization and death.  Infants, older adults, and those with serious underlying diseases (COPD, heart failure, etc) are at higher risk of serious infections and adverse outcomes.  An estimated 4-10% of older adults contract symptomatic RSV infection every year, and around 12% of these cases require hospitalization.  RSV leads to a similar number of deaths in older adults and a higher number of deaths in infants compared to influenza.  Historically, prevention has been limited, and treatment is primarily supportive care.  Monoclonal antibodies are available for infants who are at risk during the RSV season with a single dose of nirsevimab providing five months of protection from this virus. And though antiviral and monoclonal antibody treatments to prevent serious RSV-related illness in adults are being actively investigated, progress has been challenging. 

Enter the RSV Vaccine(s)!
Previous episodes of Curbsiders/Cribsiders have discussed RSV vaccines in detail, highlighting two protein-based options: Arexvy by GSK, an adjuvanted vaccine that elicits a stronger immune response but may cause more side effects, and Pfizer’s non-adjuvanted Abrysvo.  Most recently, the FDA approved Moderna’s new mRNA RSV vaccine, Mresvia.  All three vaccines target the fusion (F) protein in its pre-fusion form, enabling the immune system to neutralize the virus before it binds to and enters cells using the F protein. These vaccines are generally well tolerated, with typical vaccine side effects like injection site pain, headache, and myalgias–and surveillance studies ongoing to assess the risk of Guillain-Barré syndrome (GBS) after RSV vaccination (which occurred in a handful of trial patients), without definitive evidence of an increased risk to date.  In trials, all three vaccines offered around 80% protection against RSV infection in older adults (RENOIR, AReSVi-006, and ConquerRSV), with the two protein-based vaccines offering protection for at least two seasons (the mRNA vaccine is so new that duration of protection is unknown). Ongoing research will determine how long this protection lasts, so future guidelines may recommend repeat vaccinations. Current data suggests that real-world effectiveness reduces hospitalization or ED visits by about 70-80% in adults over 60, but more data is needed for the most vulnerable groups, including those over aged 80.  

Updated Guidelines 
This year, the CDC updated its guidelines, recommending a single lifetime RSV (Respiratory Syncytial Virus) vaccine for all adults aged 75 and older as well as those aged 60-74 at increased risk for severe RSV.  This update clarifies that repeat vaccines are not currently recommended, and simplifies the guidance compared to previous shared-decision making approaches. Patients <74 who are not at increased risk do not need an RSV vaccine, unless they are pregnant. During pregnancy, the CDC recommends RSV vaccination at 32-36 weeks of gestation between September and January to provide passive immunity to babies born during RSV season. Notably, Pfizer’s Abrysvo is the only RSV vaccine recommended for pregnant patients (see the CDC’s page on RSV immunization to protect infants, including a misadministration alert about inappropriate administration of GSK’s Arexvy vaccine to pregnant individuals).  For now, make sure you think about a single RSV vaccination in your patients 75 and older, and in those younger patients with compromised immune systems or who are pregnant – with more updates to come in the future about the need for re-vaccination.   

Read The CDC Guidelines Here!

Digestifs

Before you go….
we’ve got a few nibbles!

Consolidate your learning with a Quiz!  

This week on The Curbsiders: In line with our Digest content this month, we have a phenomenal episode, #457, this week, in which Dr. Amber Bird discusses the ins and outs of upper respiratory infections with Dr. Heublein and Dr. Witt. It’s packed with pearls about testing (who needs that extended panel?) and symptomatic treatment. 

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Comments for the Chef

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Until next time, keep that brain hole digesting! 

The Curbsiders Digest

Issue 58

Editor in Chief: Nora Taranto MD

Banner: Kate Grant  MBChB, DipGUMed

Disclosures:
Jennifer DeSalvo,  Beth Garbitelli, Molly Heublein, Hannah Smith, and Nora Taranto report no disclosures.

Kate Grant reports no disclosures. 

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