A biweekly overview of recent studies published by Institute investigators and their collaborators spans a wide variety of topics, including:

Prenatal metal exposure; vaccines and stem cell transplants; pharmacovigilance; diagnostic stewardship; sepsis guidelines; COVID-19; obesity; social determinants of health and pediatric healthcare reutilization

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.

Using maternal and cord blood to look at exposure to metal mixtures in early pregnancy
Prenatal exposure to metals has been shown to influence maternal and child health – depending on the metal, this influence can be positive or negative. Pregnancy is a period of heightened susceptibility to environmental exposures, and examining biomarkers in cord blood can help strengthen understanding of these exposures. A new Project Viva study published in Environmental Health Perspectives and co-authored by Emily Oken tests both individual and joint associations between maternal first-trimester essential and nonessential metals and second-trimester maternal and cord blood mitochondrial DNA copy number (mtDNAcn) and telomere length (TL). The team found that maternal exposure to metals such as lead, magnesium, and selenium was associated with mtDNAcn and TL in maternal second trimester and cord blood. They suggest that future work can evaluate whether these biomarkers are associated with child health. 

Institute Investigator(s): Emily Oken

Testing the staying power of differentially methylated positions and regions in cord blood
In a second Project Viva study to examine the effects of prenatal exposure to essential and nonessential metals on birth and offspring health, a team including Sheryl Rifas-Shiman, Emily Oken, and Marie-France Hivert analyzed the extent to which metals measured in maternal erythrocytes were associated with differentially methylated positions (DMPs) and regions (DMRs) in cord blood and tested if associations persisted in blood collected in mid-childhood.  The team determined that prenatal metal exposure is associated with DNAm, including DMRs annotated to genes involved in neurodevelopment, and that further research is needed to determine if DNAm partially explains the relationship between prenatal metal exposures and health outcomes.

Institute Investigator(s): Marie-France Hivert, Emily Oken

The measles, mumps, and rubella vaccine: safe when administered within two years of a hematopoietic cell transplant?
The measles, mumps, and rubella vaccine uses a weakened form of all three diseases to create a long-lasting immune response. A group of researchers, including Sanjat Kanjilal, wanted to know: is it safe to administer the MMR vaccine within two years of a hematopoietic cell transplant (HCT), also known as a bone marrow transplant? HCT results in the need for the body to rebuild immunity, which occurs in different phases, but is often viewed to take 1-2 years. The team conducted a retrospective review in patients who received an HCT at Brigham & Women’s Hospital/Dana Farber Cancer Institute between January 2017 – December 2018. Results, published in Open Forum Infectious Diseases, found that in this cohort of patients, the MMR vaccine was safe and well tolerated, with a low rate of adverse reactions.  

Institute Investigator(s): Sanjat Kanjilal
 

Continued pharmacovigilance warranted after analysis of incidence of thromboembolic events attributable to intravenous immune globulin products
A new study in the Journal of Thrombosis and Thrombolysis assessed the incidence of thromboembolic events (TEEs) attributable to intravenous immune globulin (IGIV) products in a large population-based cohort. A boxed warning concerning the risk was issued by the US Food and Drug Administration in 2013. The study team used the FDA-sponsored Sentinel Distributed Database to conduct the analysis, and found a small increase in the absolute risk of arterial TEEs following IGIV, though they caution that results should be interpreted cautiously, and that pharmacovigilance efforts should continue to assess risk.

Institute Investigator(s): Candace Fuller

Taking steps to improving diagnostic stewardship of urine cultures
Recognizing that urine cultures often lead to misdiagnosis of urinary tract infection and unnecessary antibiotics, a study team including Chanu Rhee sought to develop expert guidance on best practices for urine culture diagnostic stewardship that would optimize patient outcomes. They determined best practices by using a RAND-modified Delphi approach with a multidisciplinary expert panel. Results, including 18 guidance statements that can optimize use of the imperfect urine culture for better patient outcomes, are published in Clinical Infectious Diseases.

Institute Investigator(s): Chanu Rhee
 

A fourteen-year look at opioid use in pregnancy in 8 US health plans
A new study co-authored by Darren Toh estimated the prevalence of prescription opioid use during pregnancy in eight U.S. health plans from 2001 – 2014, a time period longer than previous studies had examined. Results, published in Pharmacoepidemiology & Drug Safety, showed that use during pregnancy was higher in Tennessee Medicaid compared to the other seven health plans, representing thousands of women during the study period. This study, along with those preceding it, suggest that future research is needed to understand how pain management can be optimized during pregnancy while minimizing risks to the pregnant mother and fetus.

Institute Investigator(s): Darren Toh

Aiming for balance: treating hospital-acquired pneumonia
While hospital-acquired pneumonia (HAP) is the most common and mortal healthcare-associated infection, it is also one of the most common drivers of broad-spectrum antibiotic use in hospitals. A new commentary in Infection Control & Hospital Epidemiology led by Michael Klompas takes on the critical issue of the need to find balance when treating HAP. The authors discuss the pitfalls of under- and over-treatment, and emphasize that prevention is the best way to minimize overtreatment.

Institute Investigator(s): Michael Klompas

Evaluating SEP-1 guidelines: did they optimize patient outcomes?
New sepsis reporting guidelines, SEP-1, were implemented in 2015, with the aim of optimizing patient outcomes. Understanding if/how these guidelines affect patient care and outcomes is critical. A new study in JAMA Network Open led by Chanu Rhee with Michael Klompas, Rui Wang, and Tingting Yu looked at 117,510 adult patients who were admitted to 114 US hospitals with clinical evidence of suspected sepsis between October 2013 – December 2017.  Results show that SEP-1 implementation in October 2015 was associated with an immediate increase in lactate testing rates, no significant change in already-increasing rates of broad-spectrum antibiotic use, and no change in the combined outcome of in-hospital death or discharge to hospice. These findings suggest that alternate approaches to improving mortality for patients with sepsis are warranted.

Institute Investigator(s): Michael Klompas, Chanu Rhee, Rui Wang, Tingting Yu

Evaluating the consequences of viral evolution: SARS-CoV-2 edition
Many studies have examined the impact of SARS-CoV-2 variants on neutralizing antibody activity after they have become dominant strains. In a new study in Science, a team including Sanjat Kanjilal evaluated the consequences of further viral evolution and demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, are more resistant to neutralization by therapeutic antibodies and serum from vaccine recipients. Furthermore, they identified an antibody that binds the RBD core to neutralize pseudotypes for all tested variants but show that the RBD can acquire an N-linked glycan to escape neutralization. Results show that variants will continue to emerge.

Institute Investigator(s): Sanjat Kanjilal

COVID-19 shines a spotlight on health disparities
Few population-level studies have examined the effects of COVID-19 on childhood obesity prevalence. Using MDPHnet, a research team led by fellow Allison Wu examined obesity prevalence in a fixed cohort of children and adolescents in three periods ranging from 2018 to 2020. Results, published in JAMA Pediatrics, showed that while childhood obesity was on the rise before the emergence of COVID-19, Massachusetts youth saw a greater increase in obesity during the COVID-19 pandemic. The research team urges that further research be conducted to further examine the pandemic’s impact on obesity, as research coming out of the pandemic continues to magnify disparities.
 

Institute Investigator(s): Izzuddin Aris, Noelle Cocoros, Marie-France Hivert, Michael Klompas, Allison Wu
 

Validating diagnosis codes that identify COVID-19 patients in health care claims data
Health plan claims are a great source for the longitudinal study of disease – but only if they are linked to the applicable laboratory results, as is needed to assess COVID-19 at a population level. A new FDA Sentinel study led by Sheryl Kluberg assessed the validity of ICD-10-CM diagnosis codes for identifying patients hospitalized with COVID-19 in U.S. claims databases, compared to linked laboratory results. The team identified patients hospitalized with COVID-19 according to five ICD-10-CM diagnosis code-based algorithms. They calculated the positive predictive value and sensitivity of each algorithm relative to laboratory test results and stratified results by data source type and across three time periods. Study results, published in Pharmacoepidemiology & Drug Safety, support the use of code U07.1 to identify hospitalized COVID-19 patients in U.S. claims data.

Institute Investigator(s): Noelle Cocoros, Sheryl Kluberg, Darren Toh

Using the Childhood Opportunity Index to describe the association between pediatric readmissions and social determinants of health

A new study co-authored by Alon Peltz takes a closer look at pediatric reutilization through the lens of the Childhood Opportunity Index, which helps estimate social determinants of health. The study included children 0-17 years of age within 48 children’s hospitals in 2019. Results, published in Academic Pediatrics, suggest that children living in low opportunity areas had greater 30-day readmissions and Emergency Department (ED) revisits. Results suggest that a broader approach, including policy and system-level change, is needed to effectively reduce readmissions and ED revisits.

Institute Investigator(s): Alon Peltz