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RESEARCH BRIEFS
Early Treatment of Seizure Patients May Limit HarmPatients who suffer the prolonged or repeated seizures of status epilepticus have the best chance to avoid serious neurologic damage if the seizures are arrested quickly, and the earliest opportunity to treat them often falls to paramedics. A study led by HMS dean for medical education Daniel Lowenstein and published in the Aug. 30 New England Journal of Medicine shows that emergency medical personnel can safely and effectively treat status epilepticus patients with benzodiazepine tranquilizers—either lorazepam (Ativan) or diazepam (Valium). The investigators looked at outcomes among 205 patients in San Francisco who were randomized to receive either diazepam, lorazepam, or placebo from paramedics responding to an emergency call. The study was done while Lowenstein was at the University of California, San Francisco, and co-authors are at UCSF, San Francisco General Hospital, the San Francisco Fire Department, and Carondelet Health Network in Tucson, Ariz. In 59 percent of patients who received lorazepam, seizures stopped before they arrived at the hospital emergency department, compared with 43 percent of patients treated with diazepam and only 21 percent of those who got placebo. Patients who received lorazepam also experienced shorter seizures than the other groups. The researchers reported respiratory and cardiovascular complications—common side effects of benzodiazepines—in 11 percent of the lorazepam group, 10 percent of the diazepam group, and 23 percent of the placebo group, suggesting that respiratory complications of the seizures themselves may be more pronounced than those caused by the study drugs. Based on these results, the authors recommend lorazepam for emergency treatment of status epilepticus. However, they note that lorazepam, unlike diazepam, requires refrigeration (or more frequent restocking) to ensure the drug's potency. Because many patients were still in status epilepticus despite treatment, they recommend studies using higher doses of the two drugs to define the optimal treatment for these patients. —Tom Reynolds
Racial Disparities and Overuse Shown in Cardiac RevascularizationHealth care researchers have observed racial disparities in the use of cardiac revascularization procedures to treat coronary artery disease. But it has been unclear to what extent these differences represent overuse by white patients or underuse by African-American patients. A new study led by Harvard researcher Eric Schneider, instructor in health policy and management at HSPH and in medicine at HMS, suggests that overuse of the procedures—coronary artery bypass graft surgery and percutaneous transluminal coronary angioplasty—is greater among white patients than other racial groups, accounting for some but not all of the variation. Co-authors of the article in the Sept. 4 Annals of Internal Medicine include HSPH's Lucian Leape, adjunct professor of health policy, and Arnold Epstein, the John H. Foster professor and chair of Health Policy and Management; Joel Weissman, HMS assistant professor of medicine at Massachusetts General Hospital; and collaborators at Vanderbilt and Brown universities. They reviewed records of 3,960 Medicare beneficiaries who had diagnostic coronary angiography in 1991 and 1992 at 173 hospitals in five U.S. states. Of these patients, 1,486 underwent revascularization within 90 days and had sufficient records available to allow its appropriateness to be rated. Overall, rates of revascularization were significantly higher among white patients than African-American patients for both angioplasty (23 percent vs. 19 percent) and bypass surgery (29 percent vs. 17 percent). White patients were more likely than African-American patients to receive an angioplasty rated as inappropriate (15 percent vs. 9 percent), although the difference was statistically significant only for men. Rates of inappropriate bypass surgery were 10 percent in both groups. Overuse of both procedures varied significantly by state, with rates of inappropriate use ranging from 4 percent to 24 percent for angioplasty and 0 percent to 14 percent for bypass surgery. "Future studies should evaluate the role of underuse of procedures among African-American patients as a cause of racial disparity in revascularization and explore the factors that contribute to large regional differences in inappropriate use," the authors write. Appearing in the same journal issue is a literature review of racial differences in the use of invasive cardiovascular procedures, written by Nancy Kressin of the Bedford VA Medical Center and Boston University School of Public Health, and Laura Petersen of the Houston VA Medical Center and Baylor College of Medicine, Houston. —Tom Reynolds
Some Residents Feel Unprepared for Certain Patient PopulationsMedical education appears to be in better health than many have given it credit for. Despite a general perception that physician training has been deteriorating under the stress of managed care and other pressures, senior residents queried in a recent survey report they feel well prepared to manage most of the common medical conditions they would encounter in their career. They felt less prepared, however, to provide certain types of care, such as treating substance abuse patients or patients in nursing homes. The findings appear in the Sept. 5 Journal of the American Medical Association. David Blumenthal, HMS professor of medicine, Joel Weissman, assistant professor of medicine—both at Massachusetts General Hospital—and their colleagues surveyed 2,626 residents in their last year of training in a wide range of U.S. academic health centers. Nearly 90 percent of residents, who were drawn from eight specialties (internal medicine, pediatrics, family practice, obstetrics/gynecology, psychiatry, general surgery, orthopedic surgery, and anesthesiology), reported that they felt "very prepared" or "somewhat prepared" to undertake most of the common clinical tasks associated with their specialty. For example, 99 percent of primary care residents felt confident that they could treat inpatients, 94 percent to treat outpatients or elderly patients, and 91 percent to treat chronically ill patients. Significant proportions of residents felt less confident about their ability to provide specific types of care. Among primary care residents, only 75 percent felt prepared to treat substance abuse patients, 70 percent to treat HIV/AIDS patients, and 66 percent to treat nursing home patients. "These findings suggest that [academic health centers] now face the challenge of ensuring the quality of training for nontraditional educational experiences," the authors write.
Potential Diabetes Culprit IdentifedKeeping blood sugar at just the right level requires balancing sugar uptake by peripheral tissues—muscle and fat—and its production by the liver. But the balance is thrown off in diabetes. Sugar production, or gluconeogenesis, soars as sugar storage falls off. Researchers have been looking for the molecular actors that bring about this insidious rise in blood sugar. Now, HMS researchers working with scientists at other institutions have identified an unexpected player. Gluconeogenesis is stimulated by the hormone glucagon and suppressed by insulin. Glucagon works by turning on the genes for gluconeogenic enzymes, but it is not known which transcription factors regulate these genes. In a pair of papers published in the Sept. 13 Nature, Bruce Spiegelman and colleagues report that gene regulation is achieved by cAMP response element binding protein (CREB) working through a transcriptional co-activator PGC-1. Though the role of CREB was suspected, the discovery of PGC-1's part in the gluconeogenic drama is surprising. "PGC-1 wasn't even known to be expressed significantly in the liver or to be related to gluconeogenesis," said Spiegelman, HMS professor of cell biology at the Dana–Farber Cancer Institute. He and his colleagues found that PGC-1 is strongly induced in mouse livers in three murine models of diabetes, and it is induced by the same substances that normally stimulate gluconeogenesis, namely glucagon and cAMP. "Almost everything that turns on gluconeogenesis turns on PGC-1," said Spiegelman. Perhaps most impressive, when expressed in liver cells both in vitro and in vivo, PGC-1 turns on the entire program of gluconeogenic genes. The findings suggest that drugs designed to block PGC-1 might be one way to prevent blood sugar from rising in people with diabetes. "If there was a way to suppress gluconeogenesis, that would be a good antidiabetic therapy," he said. —Misia Landau |
