This month’s overview of recent studies published by Institute investigators and their collaborators spans a wide variety of topics, including:

Antibiotics: for sepsis, and for pneumonia; vaccine safety surveillance; epigenetics and childhood obesity; the genetics of asthma; telemedicine for allergy and asthma

For all faculty publications, see our Publications page. For up-to-date media coverage and research findings, visit In the Media, and follow us on Twitter. To search for a subject matter expert, visit our Investigator Directory.
 

Testing an opt-out program to decrease unnecessary antibiotics
Sepsis guidelines recommend daily review to de-escalate or stop antibiotics in appropriate patients. A randomized controlled trial (RCT) co-authored by Michael Klompas evaluated an opt-out protocol to decrease unnecessary antibiotics in patients with suspected sepsis. The team evaluated non–intensive care adults on broad-spectrum antibiotics despite negative blood cultures at 10 US hospitals from September 2018 through May 2020. Results, published in Clinical Infectious Diseases, showed that an antibiotic opt-out protocol that targeted patients with suspected sepsis resulted in more antibiotic discontinuations, similar days of therapy when antibiotics were continued, and no evidence of harm.

Institute Investigator(s): Michael Klompas

Real-world vaccine surveillance assures the safety of the Recombinant Zoster Vaccine
Recombinant zoster vaccine (RZV) was licensed in 2017 to prevent herpes zoster (shingles) and its complications in older adults. In a new prospective, postlicensure Vaccine Safety Datalink study using electronic health records co-authored by Katherine Yih, a team sequentially monitored a real-world population of adults aged ≥50 years who received care in multiple US Vaccine Safety Datalink health systems to identify potentially increased risks of 10 prespecified health outcomes, including stroke, anaphylaxis, and Guillain-Barré syndrome (GBS).

Results, published in American Journal of Epidemiology, provide additional reassurance about the overall safety of RZV. Despite a large sample, uncertainty remains regarding potential associations with GBS due to the limited number of confirmed GBS cases observed.

Institute Investigator(s): Katherine Yih

Less is More: A 7-day course of antibiotics is the evidence-based treatment for Pseudomonas aeruginosa Ventilator-associated Pneumonia
Recommendations for the length of antimicrobial therapy for ventilator-associated pneumonia (VAP) due to Pseudomonas aeruginosa (PsA) have changed over time. The most recently update came in 2016, when a shorter course (7 days) became the recommendation, reduced from 14-21 days. In a new editorial in Clinical Infectious Diseases, a trio including Michael Klompas refute the argument of Albin, et al, who suggest that further research should be done to address whether less is actually more.

The team uses two existing high-quality randomized controlled trials (RCTs) to inform their practice to justify standing by their recommendation from the 2016 guidelines: they posit that indeed, less is more, and that a 7-day course of antibiotics is the evidence-based treatment for PsA-VAP.

Institute Investigator(s): Michael Klompas

How genes may assign adiposity in childhood: a study
Growing evidence suggests that the SERPINE1 gene, which provides instructions for making a protein called plasminogen activator inhibitor 1 (PAI-1) may have a causal role in adipogenesis, the process by which fat-laden cells accumulate as adipose tissue. DNA methylation (DNAm) is an epigenetic mechanism regulating gene transcription and likely involved in the fetal programming of childhood obesity. A study co-authored by Marie-France Hivert aimed to assess the associations between PAI-1 gene (SERPINE1) DNAm, plasma PAI-1 levels, and adiposity at five years of age. The team assessed the association between plasma PAI-1 levels and different markers of adiposity at 5 years of age, then investigated the association between SERPINE1 DNAm levels in blood cells and adiposity markers and plasma PAI-1 levels at 5 years of age. Study results, published in International Journal of Molecular Sciences, suggest an association between epigenetically mediated regulation at the SERPINE1 locus and fat mass growth in girls.

Institute Investigator(s): Marie-France Hivert

Linking prenatal exposure to maternal insulin sensitivity to childhood obesity
Prenatal exposure to maternal hyperglycemia has been associated with childhood obesity, but what is it about maternal insulin physiologic components that contribute to this association? A team led by former fellow Nidhi Ghildayal with senior author Marie-France Hivert evaluated the association between maternal insulin sensitivity during pregnancy and adiposity measures in childhood. Using the Gen3G cohort, they tested associations between maternal insulin sensitivity measures at ~26 weeks of pregnancy and child adiposity measures, including dual-energy X-ray absorptiometry body composition and anthropometry (body mass index and waist circumference) at ~5 years in 422 mother-child pairs. Results, published in Pediatric Obesity, suggest that maternal insulin sensitivity during pregnancy may contribute to increased risk for higher offspring central adiposity in middle childhood.

Institute Investigator(s): Marie-France Hivert

Could Telemedicine Be Here to Stay? Understanding the Rapidly Changing Landscape of Telemedicine in Allergy and Immunology Practice
In a new editorial in The Journal of Allergy and Clinical Immunology: In Practice, a trio including senior author Ann Wu discuss the utility – and the challenges – of the increase in adoption of telemedicine specifically in the area of allergy and immunology practice.

They note that while several benefits of telemedicine have been identified across specialties (eg, convenience, decreased wait times, and transportation time), a specialty- and disease-specific approach can be useful in optimizing telemedicine care for patients. Also, challenges lie in bridging disparities in telemedicine. They posit that overall, as the landscape continues to grow and adapt, telemedicine is a promising addition to the allergy and immunology practitioner’s clinical toolkit.

Institute Investigator(s): Ann Wu
 

Sequential Data-Mining for Adverse Events after Recombinant Herpes Zoster Vaccination Using the Tree-Based Scan Statistic
Tree-based scan statistics have been successfully used to study the safety of several vaccines without prespecifying health outcomes of concern. A team led by Katherine Yih and senior author Judy Maro looked at nearly 1 million Recombinant Herpes Zoster (RZV) vaccinations using this method. Results, published in American Journal of Epidmiology, showed statistically significant signals only for unspecified adverse effects or complications following immunization, all in the sequential analyses using the primary, days 1–28 risk window. The team also notes that although the method requires prespecification of the risk window of interest and may miss some true signals detectable using the tree-temporal variant of the method, it allows for early detection of potential safety problems through early initiation of ongoing monitoring.

Institute Investigator(s): Judy Maro, Katherine Yih

Inheriting asthma: taking a closer look at why it may be passed down within families
Why is it highly likely that if one has asthma, one’s offspring is likely to also have it? Its established genetic associations fail to explain the high estimated heritability, and the prevalence of asthma differs between populations and geographic regions. Robust association analyses incorporating different genetic ancestries and whole-genome sequencing data may identify novel genetic associations, and a team including Sharon Lutz decided to take this approach in a new study published in Human Molecular Genetics. Results of their family-based whole-genome sequencing analysis identified three novel genetic loci for childhood-onset asthma. The team suggests that follow-up analyses are needed to understand the functional mechanisms and generalizability of these associations.

Institute Investigator(s): Sharon Lutz