Digest 57: Numerous Pneumo Vaxes–Expanding our understanding of preventing pneumococcal infection.

September 20, 2024 | By Nora Taranto

Welcome Back to The Curbsiders Digest!

In this issue, numerous pneumo vaxes–expanding our understanding of preventing pneumococcal infection. Plus Intranasal Epi, Continuous Oxygen, Finerenone, and so much more.   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 57

09/20/2024

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; Laura Glick MD; Hannah Smith MD 

• Intranasal Epi – Is it the Future? In August, the Food and Drug Administration (FDA) approved Neffy, the first nasal spray for the treatment of Type 1 allergic reactions including anaphylaxis.  Neffy was approved for adults and children > 30 kg  based on 4 studies in a total of 175 healthy adults (and one study of children) that compared epinephrine concentrations in the blood following Neffy versus approved injectable epinephrine products. There were comparable epinephrine blood concentrations between Neffy and the already approved epinephrine products for both the adults and children studied. Neffy is administered as a single dose intranasally, with the option for a second rescue dose if needed, in the same nostril.  Patients with nasal polyps or history of nasal surgery might have altered absorption of Neffy; injectable epinephrine may be preferred for these patients. (HS) 
• Concerning new data on the efficacy of tubal ligation. Tubal ligation might not actually be as effective as previously thought, according to a new observational study published in NEJM Evidence. This study included data from the National Survey of Family Growth and included over 4,000 women aged 15-44 in US representative samples who had tubal ligation procedures between 2002 and 2015. Over four time cohorts (2002, 2006-2010, 2011-2013, and 2013-2015), rates of pregnancy within one year after tubal sterilization ranged from 2.9% (2006-2010) to 5.2% (2013-2015).  12-33% participants reported an ectopic pregnancy after tubal ligation.  Demographic factors and medical conditions were not significantly associated with higher tubal sterilization failure rates. Notably, the survey did not distinguish between the type of sterilization procedure performed (clip, tubal removal, or other methods). (LG)
• The Oxygen Debates: Is More Better? There may not be any advantage to long-term oxygen therapy for 24 hours per day, compared to 15 hours per day, in patients with chronic, severe hypoxemia. In the REDOX trial just published in NEJM, 241 patients with severe hypoxemia (71% from COPD) were randomly assigned to receive long-term oxygen therapy for 24 hours daily or 15 hours daily. After 12 months, there was no significant difference in the risk of hospitalization or death between the two groups (mean rate of 125 events/100 person-years in both groups; hazard ratio, 0.99; 95% confidence interval, 0.72 to 1.36; P=0.007 for non-superiority). (LG) 
• Another win for GDMT in HFpEF and HFmrEF?  The steroidal mineralocorticoid receptor antagonist finerenone was recently studied in an international, double-blind trial, just published in NEJM. In FINEARTS-HF,  >6000 adults with heart failure and an ejection fraction >40% were randomized 1:1 to receive finerenone (either 20 or 40 mg daily) or placebo, in addition to usual therapy. The primary outcome included a composite of total worsening heart failure events and cardiovascular-related mortality. Those receiving finerenone had significantly fewer primary outcome events compared to placebo after median follow-up of 32 months (rate ratio 0.84, CI 0.74 – 0.95, p=0.007), with a significant reduction in worsening heart failure events in particular.  Finerenone use was associated with a slight increase in patient-reported health status by KCCQ total symptom score, but also an increased risk of hyperkalemia and elevated creatinine. (JD) 
• In thE SP(i)RIT of improving hypertension control, The Lancet recently published an open-label, blinded-outcome trial comparing intensive and less-intensive blood pressure control in high-risk patients.  In ESPRIT, 11,255 adults > 50 with elevated blood pressure and high cardiovascular risk (with known cardiovascular disease or two cardiovascular risk factors) were randomized to intensive blood pressure treatment with systolic blood pressure (SBP) goal <120 mmHg or standard treatment with an SBP goal <140 mmHg. The primary outcome was a composite of myocardial infarction, revascularization, hospitalization for heart failure, stroke, or cardiovascular-related mortality assessed via intention to treat analysis. After median follow-up of 3.4 years, the primary outcome occurred significantly less with intensive treatment compared to standard of care (events in 9.7% vs 11.1% of patients, respectively, p=0.028), without effect differences noted based on stroke history or diabetes status.  There were more syncopal events with intensive treatment, but no significant difference in rates of hypotension, acute kidney injury, electrolyte abnormality, or injurious falls. See an excellent discussion of this trial, in the context of SPRINT, in Neph JC. (JD) 

Palate Cleanser

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

The old adage of laughter as the best medicine still rings true, even in treating symptomatic dry eye disease, as evidenced by a study recently published in BMJ. This non-inferiority trial randomized 299 adults aged 18-45 years with symptomatic dry eye disease 1:1 to artificial tears (control) or laughter exercise for eight weeks, in which participants chanted the phrases “Hee hee hee, hah hah hah, cheese cheese cheese, cheek cheek cheek, hah hah hah hah hah hah” 30 times per five minute session four times daily.  Laughter exercise was noninferior to the control group, with similar mean changes in ocular surface disease index score at eight weeks. Additionally, laughter exercise significantly improved non-invasive tear break up time. Next time you reach for a bottle of artificial tears, think about watching your favorite sitcom or comedian’s special instead!

– Jennifer DeSalvo MD 

The Main Course

Molly Heublein MD 

What’s new in Pneumococcal Vaccination? 

Pneumonia vaccines for adults weren’t confusing already, right?  Well, just to add to the mix, a newly approved Pneumococcal Conjugate 21 vaccine (PCV21) is now available! The Streptococcus pneumoniae, or pneumococcus, bacterium causes both non-invasive pneumococcal disease (pneumonia) and invasive pneumococcal disease (IPD) with bacteremia or meningitis, and is a significant cause of morbidity and mortality, particularly in older or at risk patients. It is spread from person to person via airborne droplets, and certain serotypes (a.k.a. strains) of the bacterium cause most cases of IPD.  At their June 2024 meeting, the CDC’s Advisory Committee on Immunization Practices (ACIP) recommended that all adults who are eligible for a pneumococcal conjugate vaccine could receive PCV21 as an option.  

Vaccination for pneumococcal disease is already highly effective, possibly more from herd immunity than direct vaccination of adults. In the US, rates of IPD among older adults have already fallen about 50% since routine childhood vaccination was instituted in 2000, and rates due to serotypes covered by PCV 7 and 13 (the vaccines given to young kids) have seen even greater reductions (see Figures 1/2 in the CDC’s Manual for the Surveillance of Vaccine-Preventable Diseases).   With this reduction in illness due to serotypes covered by childhood vaccines, a greater percentage of adult pneumococcal disease is from previously non-covered serotypes.  Enter PCV21!  

The Details

As a quick reminder, we have two basic types of pneumococcal vaccines. Polysaccharide vaccines, like PPSV23, are harder for the immune system to recognize and don’t activate T cells, limiting memory B cell responses. On the other hand, conjugate vaccines (PCV7, 13, 15, 20, or 21), display bacterial polysaccharides attached to a protein, triggering a more robust immune response.  Conjugate vaccines promote memory B cell production, and lead to longer-term immunity.   Until recently, PCV vaccines targeted fewer serotypes (e.g. 7, 13, 15…) than PPSV23. While they triggered a stronger immune response, they offered narrower coverage.

PCV21 was approved based on data from STRIDE-3, which evaluated primarily non-clinical outcomes and in which PCV21 demonstrated non-inferiority to PCV20 based on immunogenicity response (antibody titers).  PCV20, in turn, was approved based on noninferiority for similar biochemical endpoints to PCV13, which had shown a 45% reduction in community acquired pneumonia and a 75% reduction in IPD in adults> 65 due to covered serotypes.  PCV21 was well tolerated, without serious side effects observed.

PCV21 is more than just “PCV20+1”! PCV21 covers 21 strains, including 11 unique serotypes not in PCV20.  Highlighted at the ACIP meeting, PCV20 covers 54% and PCV21 covers 85% of the serotypes causing IPD in adults>65.  One downside of PCV21 is that it does not cover serotype 4 (which is included in PCV20 and PPSV23).  Serotype 4 is a major cause of invasive disease in certain populations, especially those in some Western US regions and people experiencing homelessness.  

Bottom line:

PCV21 offers an exciting new option to extend prevention of IPD in our at-risk adults due for pneumonia vaccination, though PCV20 and other combinations of pneumonia vaccines remain appropriate options.  While the CDC hasn’t yet publicly adopted the ACIP’s recommendation, they have incorporated the recommendation into the CDC’s PneumoRecs App, which can help you to determine if your patient should be (re)vaccinated, and with which vaccine.  Currently only about 20% of adults aged 19-64 with risk factors have received appropriate pneumococcal vaccination, and significant racial disparities exist in vaccination rates among people over age 65.  So be sure to counsel eligible patients on pneumococcal vaccination in their next PCP appointment! 

Read The June ACIP Recommendations Here!

Digestifs

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

Consolidate your learning with a Quiz! 

This week on The Curbsiders: Join us for Episode #453 with Dr. Carlin Senter, who talks us through common sports injuries–from diagnosis to management.  Concussions and hip pain are the focus of this episode, which you are almost sure to see in your primary care clinic.  It’s a high yield one, folks!   

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The Curbsiders Digest

Issue 57

Editor in Chief: Nora Taranto MD

Banner: Kate Grant  MBChB, DipGUMed

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

Kate Grant reports no disclosures.

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