#529 - Varicella vs. Zoster, New CVD Risk Calculator, Vacation Rx?

Questions from Colleagues

1)  Varicella and Zoster – same virus, different approaches

Over the past few weeks, I’ve gotten several questions about varicella and zoster vaccinations for adults. And last week’s Take 3 (# 528) apparently stoked more questions:

• Can we give recombinant zoster vaccine (RZV, Shingrix) with a negative varicella titer?
• Is there any data on folks who had live zoster vaccine (ZVL, Zostavax) in the past needing just one dose of RZV?
• Should we offer varicella vaccine (VAR) after an RZV or ZVL vaccine?
•  Is it ok to check a varicella titer after a RZV (or ZVL) vaccine?
• Will the RZV (or VZL) vaccine influence the varicella titer?

VAR and RZV are both vaccinations against the varicella-zoster virus, so it seems as though there should be a simple, logical connection between the two, but real life is more complex than that.

• The Centers for Disease Control and Prevention (CDC) recommends the live VAR vaccine at 12-15 months and again at 4 years alongside the live MMR vaccine.
• They recommend the recombinant RZV (which is not live) starting at age 50 in a two-dose series and have withdrawn the recommendation for ZVL, which is no longer manufactured.
• The CDC recommends AGAINST checking varicella titers prior to RZV vaccination in the United States because approximately 98% of people eligible for the vaccination will have either been vaccinated or been exposed to the virus. Titers from vaccination may be too weak to detect but can still provide sufficient prior immunity to build upon with the RZV vaccine.

Where this gets tricky is if we know that a patient eligible for RZV has a negative varicella titer status in the absence of prior immunization. In that case, the CDC recommends the complete VAR vaccination series (2 doses separated by at least 4 weeks) followed eight weeks later by a 2 dose RZV vaccination series (separated by 2-6 months).

There is no data on the question of only a single dose of RZV after ZVL. Titers are NOT yet recommended as a reliable way to assess the zoster immunity conferred by RZV, so there is no easy way to study zoster immunity except by a clinical outcome study…and that study has apparently not been done.

The rest of the questions above deal with preventing varicella in patients over 50 years who have received RZV. This is an area of active study in the literature, but currently the recommendation is to not create situations in which you are worried about varicella immunity after RZV (or ZVL) vaccination. This issue will mostly arise in healthcare workers who are checked for varicella immunity as part of their work requirements. VAR vaccine should not be given after a RZV (or VZL) vaccine – there should be no reason to give it and it has not been studied. There is no current recommendation for checking varicella titers after RZV to document immunity, despite some studies showing that RZV does increase varicella titers. The remainder of the population should be getting RZV because of presumed immunity to varicella.

John’s Comments: This is a clinical area in transition, and the number of edge cases outweigh the available evidence. The CDC is getting by with blanket recommendations in the absence of specific evidence, but hopefully that will change with more study. For the vast majority of our patients the basic recommendations should suffice: ensure childhood vaccination, re-vaccinate women of reproductive age immediately after delivery if varicella titers checked during pregnancy are negative, and give RZV to patients over 50 without checking titers.

References:

1.  Prevention of Varicella: Recommendations of the Advisory Committee on Immunization Practices (ACIP). Accessed January 23, 2024. Link

2. Dooling KL. Recommendations of the Advisory Committee on Immunization Practices for Use of Herpes Zoster Vaccines. MMWR Morb Mortal Wkly Rep. 2018;67. Link

3. 9 Important Things To Know About Shingles Vaccination - NFID. https://www.nfid.org/. Accessed January 22, 2024. Link

From the Literature and the American Heart Association (AHA)

2)  New Risk Calculator for CVD, ASCVD, and HF

Obesity, diabetes, and chronic kidney disease (CKD) are each associated with a high burden of cardiovascular disease (CVD) morbidity and mortality, and they commonly co-occur and disproportionately affect disenfranchised populations (eg, underrepresented racial and ethnic groups).  Given the complex interplay of these chronic conditions, a comprehensive focus on CVD prevention that conceptually and therapeutically integrates prevention and management of obesity, diabetes, and CKD has been sought.   This has required moving beyond individual risk factor management approaches and toward a more comprehensive framework.  As covered in last week's Take 3, the AHA recently issued a Presidential Advisory introducing the term cardiovascular-kidney-metabolic (CKM) syndrome and outlining a staging process that reflects the spectrum of risk as well as opportunities for prevention and care optimization at each stage.    

The AHA followed up this Advisory with the introduction of a new CVD risk calculator, the PREVENT^TM (Predicting Risk of CVD Events) Online Calculator, the first in 10 years.  Intended for primary prevention, the calculator provides 10-year risk estimates for total CVD (composite of atherosclerotic CVD and heart failure) for individuals 30-79 years of age and as a new addition for risk calculators, provides 30-year risk estimates for individuals 30-59 years of age.  The risk equations were derived and validated in a large, diverse sample of over 6 million individuals.  Additionally, they include estimated glomerular filtration rate as a predictor and adjust for competing risk of non-CVD death.  Add-on models that incorporate hemoglobin A1c, urine albumin-to-creatinine ratio, and social determinants of health (social deprivation index) are currently under development and the calculator will be updated when these are available. 

As with previous risk calculators, it is hoped that the ability to estimate absolute risk may assist and guide clinicians and patients in shared decision-making for interventions targeting lifestyle behaviors and consideration of pharmacotherapies.

Mark’s Comments:

The ability to more precisely estimate risk can certainly be helpful in our clinical practice, remembering, of course, these are just estimates.  A concern of previous calculators is that that age was overemphasized in the equation, and the intention of having such a large data set is to help attenuate this.  In playing with the calculator and my personal health data, even subtle changes in age still appear to have significant impact.  Another challenge with this calculator is that eGFR measurements go up to 140, whereas many labs (ours included) presently only report “normal” eGFR as “>90.”  This also has an impact on the calculations.

Finally, in the 3^rd reference below, some of the enthusiasm for this new calculator went a bit over the top, including this statement; “So, for instance, pediatricians can screen and stage CKM risks beginning at birth”; and this quote, “I am giving you a medication for 40 years that may have some minor side effects to prevent you from having a stroke in 20 years that will have major side effects.”  In our enthusiasm for prevention, here’s hoping we don’t get way ahead of the evidence and further advance our “pill anticipating any ill” culture.

References:

• Khan SS et al.  Novel prediction equations for absolute risk assessment of total cardiovascular disease incorporating cardiovascular-kidney-metabolic health: a scientific statement from the American Heart Association.  Circulation. Published online November 10, 2023.  Link
• PREVENT Online Risk Calculator:  Link
• Larkin H.  What to Know About PREVENT, the AHA’s New Cardiovascular Disease Risk Calculator.  JAMA. 2024;331(4):277-279. Link

From PeerRxMed ( www.PeerRxMed.org )

3)  Vacation Rx

“What I realize (and our patients will never know), what they don’t teach in medical school is how to really take a vacation.”  Pam Lenkov, MD from her poem "Away Time" in her commentary “How to Take a Vacation.”

When is your next vacation?   And the one after that?  In our fast-paced professional world, we often find ourselves in a perpetual state of unending demands and “to do’s”, making the need for quality downtime not just a luxury, but a necessity for well-being and sanity.  At the same time, many find it very challenging to exactly that, often waiting until they “need” a vacation before scheduling one.  Yet, if you wait to take a vacation until you “need it,” you’ve waited too long, because most of your vacation will be spent in “recovery” rather than “rejuvenation” or “renewal.”   While recovery is sometimes required, prevention of the need for recovery is a much-preferred option.

Indeed, we clinicians are notorious for taking little if any vacation, and in many groups, the importance of taking regular vacation has not been role-modeled or encouraged.  Our reasons for not doing so are many, and on the surface seem rational, including patient care commitments and our sense of dedication, staffing shortages, financial considerations, poorly coordinated coverage, the inability to truly unplug, and the dread of returning to all the work that has piled up while we were gone. 

The challenge, however, is that numerous studies have shown that taking a vacation can have important and necessary physical and mental health benefits, including lower stress, a better outlook on life, and more motivation to achieve goals.  Adding to that body of research is a recent study published in JAMA Open Network.  The authors found that 60% of physicians who responded to a national survey took 3 or less weeks of vacation per year including 20% who took 1 week or less.  Additionally, 70% of those who did get away worked on a typical vacation day.  They concluded that taking more than 3 weeks of vacation per year and having full EHR inbox coverage while on vacation were associated with lower rates of burnout, whereas spending 30 minutes or longer per vacation day on patient-related work was associated with higher rates of burnout.  This, of course, is not good news.

As a response in the health system where I work, our department has begun to provide centralized inbox coverage during vacations, focusing initially on smaller practices.  For some colleagues, having this coverage has resulted in their first fully “unplugged” vacation of their career.  And while the process is evolving and there are some glitches to be worked out, the stories of true rest, vital connection, and returning with a fresh perspective have been heartening.  In talking with one of those “never unplugged before colleagues,” she shared, “That was incredible.  I feel like a new person, and we’re like an entirely different family with me feeling a part of it rather than a perpetually distracted appendage.”  For those of you who don’t have such coverage, consider having a “vacation buddy” who can cover for you and you for them.  That’s what I’ve done for many years and still do (our central coverage does not yet cover my group). 

So, back to my original questions:  When’s your next vacation, and the one after that?  If you already have them scheduled, kudos to you!  If not, there’s no better time than now to add “taking regular extended time for rest, restoration, recreation, and relationships” to your professional toolkit.  And by making plans now, you can leave plenty of time to be more intentional about schedules and coverage.  Remember, based on the data, taking at least 3 weeks of vacation this year is not simply an important break from your responsibilities but is also an integral part of your professional commitment to health - both your patients' and your own.   And if anyone asks, just tell them it was doctor’s orders … then ask them when their next vacation is ….

______________

Mark and John

Carilion Clinic Department of Family and Community Medicine

Feel free to forward Take 3 to your colleagues. Glad to add them to the distribution list.

Email: mhgreenawald@carilionclinic.org