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

High-deductible health plan effects on those with chronic disease; food systems; COPD and cachexia; childhood adiposity as an indicator of cardiometabolic health; how paternal education impacts epigenetic aging in adolescence and mid-adulthood; regulatory approvals of pediatric cancer drugs in the US and China; bias within a hospital-wide handwashing hygiene program; using lactate levels to manage sepsis; and the link between DNA methylation changes and prenatal mercury exposure

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.

The effects of high-deductible health plans on members with chronic disease
A team led by Laura Garabedian, with Fang Zhang, Dennis Ross-Degnan, and Frank Wharam published the first study to compare enrollment in high-deductible health plans (HDHPs) between members with chronic diseases such as diabetes and cardiovascular disease and healthy members. This descriptive study with time trends used 9 years’ worth of claims data from a large national commercial insurance database. Findings, published in BMJ Open, show that HDHP enrollment increased year over year, up to over 50% by 2013. Additionally, out of pocket expenditures for HDHP members with chronic diseases were five to seven times higher than those of healthier plan members. The study team suggests that policymakers consider plan designs that keep in mind the clinically vulnerable members of HDHPs.

Institute Investigator(s): Laura Garabedian, Dennis Ross-Degnan, Frank Wharam, Fang Zhang
 

The role of the nutrition community in food systems: a report from the Annual Harvard Nutrition Obesity Symposium
Food systems – the complicated, intricate set of processes that includes the production, processing, transport, and consumption of food – are an important piece of addressing hunger, malnutrition, and social inequities throughout the globe. Global food systems were the focus of the Nutrition Obesity Research Center at Harvard and the Harvard Medical School Division of Nutrition’s 22nd Annual Harvard Nutrition Obesity Symposium. A team including Marie-France Hivert published a report synthesizing the symposium in The American Journal of Clinical Nutrition. The team suggests that the nutrition community plays a key role in food systems, with the ability to transform them through advocacy for sustainability.

Institute Investigator(s): Marie-France Hivert
 

Genetic makeup and weight loss in chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease (COPD), usually diagnosed using lung function, has become the third leading cause of death internationally. Comorbidities such as cachexia, a disorder that causes extreme weight loss, can greatly alter quality of life and lead to rising health care expenditures. A team including Sharon Lutz performed a genome-wide association study (GWAS) approach to test their hypothesis that genetic variation is associated with weight loss in COPD. Results, published in the Journal of Cachexia, Sarcopenia and Muscle, showed that the EFNA2 and BAIAP2 genes were significantly associated with weight loss in COPD study participants. They suggest that identifying the genetic variations contributing to cachexia in COPD can help inform the discovery and development of therapies that could enhance response to pulmonary rehabilitation.

Institute Investigator(s): Sharon Lutz
 

Measuring the effects of childhood weight gain on adolescent cardiometabolic health
In adults, weight gain around one’s midsection has been associated with adverse cardiometabolic health and a predictor of diabetes. However, while cross-sectional studies have examined the effects of central weight gain during midchildhood and early adolescence, few longitudinal studies have done so. A new Project Viva study led by research fellow Allison Wu with Izzuddin Aris, Marie-France Hivert, and Emily Oken and published in Obesity: A Research Journal examined waist circumference and dual-energy x-ray absorptiometry-measured visceral adipose tissue, subcutaneous abdominal adipose tissue, and trunk fat of 620 study participants. Results link greater waist circumference with cardiometabolic markers in adolescence and associate it with higher systolic blood pressure. The team suggests that monitoring central adiposity gain in children may help identify and intervene in the development of cardiometabolic health risks.

Institute Investigator(s): Izzuddin Aris, Marie-France Hivert, Emily Oken, Allison Wu

Can the discrepancy between chronological and epigenetic age be used to predict chronic disease?
We generally think of ourselves by our chronological age – the number of years we have been alive. However, epigenetic age, or biological age, measures how old our bodies seem, based on several factors, including diet, sleep, physical exercise, among others. Parental and neighborhood socio-economic status (SES) are linked to poorer health, but the biological mechanisms of this remain unclear. A new study in International Journal of Epidemiology co-authored by Emily Oken and Marie-France Hivert used three US-based and one Mexico-based cohort to examine the parental and neighborhood SES via epigenetic age acceleration, or the difference between epigenetic and chronological age. Results suggest that epigenetic age acceleration captures epigenetic impacts of paternal education independently of personal SES later in life, and could give insight into the development and prevention of chronic disease. 

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

Peer-to-peer observation in hospital hand hygiene programs: does one hand wash the other?
In the fight to keep infections at bay, hospitals employ a number of infection control and hygiene protocols, the enforcement of which is critical to their success. To be successful, a hand hygiene program relies on reliable data, though tracking and perception of compliance to protocol can be subjective. A study team including Michael Klompas examined hand hygiene compliance among professional groups within Brigham and Women’s Hospital based on whether observations were conducted by members of their own professional group versus members of a different professional group. Results, published in Infection Control and Epidemiology, indicate that compliance rates were higher when reported by members of the same professional group versus a nonpeer group. For example, doctors observing doctors reported compliance rates of 96%, compared to non-doctors who observed doctors complying at a rate of 91%. The team suggests that, to alleviate bias, hospitals should incorporate new strategies in hand hygiene observations.

Institute Investigator(s): Michael Klompas

Examining the path to cancer drug approval in two high-income countries
In high-income countries, childhood cancer has transformed from a nearly universally fatal disease to one with cures for over 80% of children fighting pediatric cancer. Two high-income countries, the U.S. and China, have encouraged the research and development of pediatric therapies and increased drug trials. However, the state of approval of traditional chemotherapy and targeted drugs in China is unclear. A team including Anita Wagner compared childhood cancer drugs approved in China and the U.S., timelines of approvals, and correlations between approved childhood cancer drugs and incidence of the indicated pediatric cancers. Through a comprehensive review published in International Journal of Cancer, the team found differences between China and U.S. in approvals of new, targeted anticancer medications. The team calls for a standardized, regulatory framework based on evidence to ensure the approval of safe and effective childhood cancer drugs across the world.

Institute Investigator(s): Anita Wagner

Understanding lactate levels to optimize sepsis diagnosis and care
Sepsis remains a leading cause of death worldwide despite ongoing advances in understanding and care. A core component of many sepsis bundles and management algorithms is measuring lactate levels as a means of estimating sepsis severity, prognosis, and and odds of recovery. As its perceived importance increases, so does the need for physicians to understand lactate physiology to correctly interpret changes in lactate levels. New work from research fellow Jeremy Weinberger and faculty members Michael Klompas and Chanu Rhee , published in Seminars in Respiratory and Critical Care Medicine, reviews lactate metabolism and the evidence behind diagnostic, prognostic, and therapeutic uses of lactate monitoring and place this in the context of evolving sepsis diagnosis and management guidelines. They show how increased lactate levels and the failure of these levels to decrease over time correlate to increased mortality in septic patients.

Institute Investigator(s): Michael Klompas, Chanu Rhee, Jeremy Weinberger

Using the epigenome to understand the lingering effects of prenatal mercury exposure
Pregnant women are cautioned to avoid exposure to mercury, which has been associated with the impairment of fetal growth. Prenatal exposure can also lead to postnatal effects. Of its many forms, methylmercury is the most toxic form of mercury. A team including Marie-France Hivert and Emily Oken examined the association between prenatal methylmercury exposure and DNA methylation in cord blood and how these associations persisted in blood up to age 8. Results, published in Environmental Research, show that prenatal methylmercury exposure and methylation differences in the MED31, GRK1 and GGH–genes involved in growth and cell cycle processes during fetal development–were related. Furthermore, the methylation differences in MED31 persist into early childhood. This was also the largest epigenome-wide meta-analysis to date evaluating the association between prenatal mercury exposure and DNA methylation in newborns and children.

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