FOCUS | March 6, 2009 | RESEARCH BRIEFS

As the United States transitions to a new administration and as the health care crisis mounts, the debate about how to buttress primary-care delivery with information technology is getting louder. While much of the attention—and controversy—is focused on how to better equip physicians, little attention seems to be aimed at equipping patients to improve their care.

A 15-month study looking at 21,860 patients and 110 primary-care physicians from 11 Harvard Vanguard health centers found that patients who received mailed reminders that they were due for colorectal cancer screenings were more likely to schedule screenings than those who did not. Forty-four percent of patients who received a reminder in the mail got screened versus 38 percent who did not—a 16 percent relative increase in screening rate. In an interesting twist, electronic reminders to physicians during office visits indicating that these same patients were due for screenings yielded no significant increase.

“We had a large group of people who needed to be screened for a very important condition. If we provided them with basic information about colon cancer and their need for screening, this approach was more effective than simply leaving it all up to the doctor,” said John Ayanian, HMS professor of health care policy and HMS professor of medicine at Brigham and Women’s Hospital. The findings appear in the Feb. 23 Archives of Internal Medicine.

“Here we see that patients can take a more active role in their health care.”

For the study, Ayanian, who is also a professor in the Department of Health Policy and Management at HSPH, and Thomas Sequist, an HMS assistant professor of health care policy and an HMS assistant professor of medicine at Brigham and Women’s Hospital, looked at a group of patients aged 50 to 80. Using data generated by an electronic health record, the researchers were able to isolate a large group of patients who were overdue for colorectal cancer screening.

One group of patients was randomly chosen to receive in the mail a personalized letter and literature on colon cancer, plus a fecal occult blood test kit and instructions for scheduling either a sigmoidoscopy or colonoscopy. The remaining patients received their usual care. Not only did 44 percent of the first group get screened, but the effect increased with age: the older, the more compliant. In fact, among patients between 70 and 80 years old, screening rates increased from 37 percent to 47 percent among those who received mailed reminders to be screened—a 27 percent relative increase.

“Getting something in the mail might seem low tech, but it was only possible because in these health centers electronic medical records already existed,” said Sequist. “People speak of primary care being in crisis and that there’s too much for physicians to get done in a regular workday. But here we see that patients can take a more active role in their health care.”

—David Cameron

Students may contact either John Ayanian at ayanian@hcp.med.harvard.edu or Thomas Sequist at tsequist@partners.org for more information.

Conflict Disclosure: The authors report no conflicts of interest.

Funding Sources: The National Cancer Institute

Gene Variant Defends Against Multiple Sclerosis

A study of more than 5,000 patients led by HMS researchers has found a gene variant that protects against multiple sclerosis, an autoimmune disease that damages the nervous system and impairs speech, cognition and motion.

“It’s a small but important step,” said David Hafler, HMS professor of neurology at Brigham and Women’s Hospital and senior author of the study.

Scientists still do not know what causes MS, but they believe there are up to 100 genes making small contributions to its onset. Only eight of those genes have been found so far, said Hafler.

In 2007, his team participated in a major study that identified two new genes tied to MS after screening the genomes of 931 families. The study also hinted at a third gene, called CD58, that seemed to be involved. Now, after analyzing the DNA of 5,326 patients, the Harvard team has confirmed that CD58 has a protective variant against MS; the study was published online Feb. 23 in Proceedings of the National Academy of Sciences. Additional tests showed that variant RNA levels, a telltale sign of the gene’s action, were higher in patients going through a remission than in those experiencing a relapse.

The CD58 variant only accounts for a small protective effect against MS, but it sheds new light on how multiple genes trigger the disease, explained Hafler. “If you have 50 genes on the same pathway, each with a small effect, that small effect becomes a big one.”

Researchers think CD58 is involved in the production of regulatory T cells, a population of immune cells that ease inflammation, one of the major symptoms of MS. The protective allele might alleviate symptoms by enhancing regulatory T cell function, said first author Philip De Jager, HMS assistant professor of neurology at BWH.

The protective variant is more common among East Asians, with around half of the population carrying it, than Europeans, with only 10 percent, said De Jager. The absence of the gene variant could explain a small part of the higher MS rate in Europeans compared with East Asians. “It has a small effect, but it’s one that we can measure,” said De Jager.

De Jager and Hafler said their hunt for new variants has already yielded three additional gene candidates that they will report shortly. “The challenge in front of us is to understand how many small variants lead to the big disease risk,” Hafler said.

—Nuño Domínguez

Students may contact Philip De Jager at pdejager@rics.bwh.harvard.edu for more information.

Conflict Disclosure: The authors declare no conflicts of interest.

Funding Sources: The National Institutes of Health and the National Multiple Sclerosis Society

IN SHORT

Don’t Bug Me

Virus alerts enter e-mail inboxes so frequently that many people just ignore them. It now appears that physicians suffer from their own version of “alert fatigue.” Saul Weingart, HMS associate professor of medicine at Dana–Farber Cancer Institute and Brigham and Women’s Hospital, and colleagues studied how 2,872 clinicians use electronic prescription systems, finding that they ignored more than 90 percent of the drug interaction alerts and 77 percent of the drug allergy alerts that popped up on their screens. This was true even when the drug alert was rated as high severity. The findings appear in the Feb. 9 Archives of Internal Medicine.

Getting the Message

It is by now a truism that tumors require a nourishing supply of blood vessels to survive, but there remains a tantalizing mystery. The endothelial cells that compose blood vessels are bombarded by a multiplicity of signals—growth factors, hormones and other molecules. As Donald Ingber, the Judah Folkman professor of vascular biology in the Department of Pathology at HMS and Children’s Hospital Boston, and colleagues discovered 30 years ago, these signals include mechanical forces exerted by the extracellular matrix. How do cells make sense of the cacophony? In the Feb. 26 Nature, Akiko Mammoto, an HMS instructor in surgery at Children’s, working with Ingber and colleagues, describes a pathway that integrates mechanical signals with chemical cues from the microenvironment. The pathway, triggered by the Rho-inhibiting enzyme p190RhoGap, modulates the activities of two antagonistic transcription factors, TFII-I and GATA-2, which together govern the expression of the angiogenesis-promoting receptor VEGFR2.

—Misia Landau

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