News – Trends – Analysis

April 20, 2015


Liberia-U.S. clinical research partnership opens trial to test Ebola treatments. In partnership with the Liberian government, the National Institute of Allergy and Infectious Diseases (NIAID) has launched a clinical trial to obtain safety and efficacy data on the investigational drug ZMapp as a treatment for Ebola virus disease. The study, which will be conducted in Liberia and the United States, is a randomized controlled trial enrolling adults and children with known Ebola virus infection.

The trial will enroll adults and children who have been admitted to Ebola treatment units in Liberia, healthcare workers who were infected with Ebola virus in West Africa and have returned to the United States for treatment, and adults and children who may have acquired Ebola infection in the U.S. through secondary transmission. All participants will receive the optimized standard of care for treating Ebola infection, which includes providing intravenous fluids, balancing electrolytes, maintaining oxygen status and blood pressure, and treating other infections if they occur. Participants will then be assigned randomly to one of two groups: the first group, the control, will continue to receive the current optimized standard of care. The second group will receive the optimized standard of care plus three separate intravenous infusions of ZMapp administered three days apart.


NIH-supported researchers map epi-genome of more than 100 tissue and cell types. Much as mapping the human genome lay the foundations for understanding the genetic basis of human health, new maps of the human epigenome may further unravel the complex links between DNA and disease. The epigenome is part of the machinery that helps direct how genes are turned off and on in different types of cells.

Researchers supported by the National Institutes of Health Common Fund’s Roadmap Epigenomics Program have mapped the epigenomes of more than 100 types of cells and tissues, providing new insight into which parts of the genome are used to make a particular type of cell. The data, available to the biomedical research community, can be found at the National Center for Biotechnology Information website.

“This represents a major advance in the ongoing effort to understand how the three billion letters of an individual’s DNA instruction book are able to instruct vastly different molecular activities, depending on the cellular context,” says NIH Director Francis Collins, MD, PhD. “This outpouring of data-rich publication provides powerful momentum for the rapidly growing field of epigenomics.”

Gene networks for innate immunity linked to PTSD risk. Researchers at the Veterans Affairs San Diego Healthcare System and University of California, San Diego School of Medicine, with colleagues in New York and the United Kingdom, have identified genetic markers, derived from blood samples that are linked to post-traumatic stress disorder (PTSD). The markers are associated with gene networks that regulate innate immune function and interferon signaling.

The researchers analyzed blood samples from 188 U.S. Marines, taken before and after deployment to conflict zones. They identified modules of co-regulated genes involved in innate immune response—the body’s first line of defense against pathogens—and interferon signaling, that were also associated with PTSD. Interferons are proteins released by host cells in response to the presence of pathogens and in this study are also shown to partake in the pathology of PTSD.

The findings, published last month in the journal Molecular Psychiatry, offer novel insights into the pathophysiology of PTSD. In clinical terms, researchers say this could lead to new ways not only to improve diagnosis and treatment of persons with the mental health condition, but to predict who might be more susceptible.

Infectious Disease

Hospital readmissions following severe sepsis often are preventable. In an analysis of about 2,600 hospitalizations for severe sepsis, readmissions within 90 days were common, and approximately 40 percent occurred for diagnoses that could potentially be prevented or treated early to avoid hospitalization, according to a study published recently in JAMA.

Patients are frequently rehospitalized within 90 days after having severe sepsis. Researchers examined the most common readmission diagnoses after hospitalization for severe sepsis, the extent to which readmissions may be potentially preventable by post-hospitalization ambulatory care, and whether the pattern of readmission diagnoses differs compared with that of other acute medical conditions.

The research team identified 2,617 hospitalizations for severe sepsis, which were matched to hospitalizations for other acute medical conditions. To gauge what proportion of rehospitalizations may be potentially preventable, ambulatory care sensitive conditions (ACSCs) were measured, which are diagnoses for which effective outpatient care may reduce hospitalization rates.

There were 1,115 severe sepsis survivors (42.6 percent) rehospitalized within 90 days. The 10 most common readmission diagnoses following severe sepsis included several ACSCs (e.g., heart failure, pneumonia, chronic obstructive pulmonary disease exacerbation, and urinary tract infection). ACSCs accounted for 22 percent of 90-day readmissions.

Readmissions for a primary diagnosis of infection (sepsis, pneumonia, urinary tract, and skin or soft tissue infection) occurred in 12 percent of severe sepsis survivors compared with eight percent of matched acute medical conditions. Readmissions for ACSCs were more common after severe sepsis as opposed to matched acute conditions and accounted for a greater proportion of all 90-day readmissions.

Industry News 

Nobel Prize winner Varmus stepping down as director of NIH’s National Cancer Institute, joining Weill Cornell. Harold Varmus, MD, who had led the National Cancer Institute (NCI) at the National Institutes of Health (NIH) for nearly five years, stepped down from his post on March 31, 2015. In 1989, Varmus was co-recipient of the Nobel Prize in Physiology or Medicine for “discovery of the cellular origin of retroviral oncogenes.”

Among Dr. Varmus’ accomplishments during his tenure as NCI director, he instituted the Provocative Questions initiative, created NCI’s new Center for Global Health, revitalized the cooperative clinical trials system, launched an initiative to find drugs that target the cell signaling pathway controlled by the RAS oncogene, led the cancer component of the Precision Medicine Initiative, and contributed many other important ideas to biomedical research.

Dr. Varmus did not rest on his laurels for long—or at all, in fact. The next day, April 1, he joined Weill Cornell Medical College’s faculty as the Lewis Thomas University Professor of Medicine. In conjunction with his appointment at Weill Cornell, Dr. Varmus, internationally recognized for his research on retroviruses and the genetic basis of cancer, will team up with the New York Genome Center (NYGC) as a Senior Associate Core Member to promote the use of cancer genomics throughout the New York region. Working with the NYGC, Dr. Varmus will strive to amplify work on cancer genomes and its application to cancer care through its consortium of member institutions.