CHICAGO—A study from the Netherlands suggests that elderly persons who receive a yearly influenza vaccination have reduced risk of death from all causes, according to a study in the November 3 issue of JAMA.

"Influenza-associated morbidity and mortality increase with age, especially for individuals with high-risk conditions," the authors provide as background information in the article. "The effectiveness of vaccination has been reported to decrease in high-risk persons. Annual influenza revaccination has been proposed as a strategy to increase vaccination effectiveness."

In this study, A.C.G. Voordouw, M.D., from Erasmus Medical Center, Rotterdam, The Netherlands, and colleagues, analyzed data from 1996 through 2002 from electronic patient records that were part of the Integrated Primary Care Information Project of Medical Informatics at the Erasmus Medical Center. The study included 26,071 persons aged 65 years or older. During the total study period, the population studied received 62,476 influenza vaccinations. The annual vaccination coverage ranged from 64 percent in 1996 to 74 percent in 1999. Influenza epidemics during the study period were of mild to moderate severity with the 2000 - 2001 season showing no clear epidemic activity.

During the study followup period, 3,485 patients died. "Overall, a first vaccination was associated with a nonsignificant annual reduction of mortality (death) risk of 10 percent, while revaccination was associated with a reduced mortality risk of 24 percent," the authors report. "Compared with a first vaccination, revaccination was associated with a reduced annual mortality risk of 15 percent. During the epidemic periods this reduction was 28 percent." The authors also found that an interruption of the annual vaccinations series was associated with a 25 percent increase in mortality risk, whereas restarting vaccination after an interruption resulted in a mortality risk reduction similar to that observed following revaccination. The authors note that "in the total population one death was prevented for every 302 vaccinations, or 1 for every 195 revaccinations."

CHICAGO—Illnesses and injuries leading to either hospitalization or restricted activity are strongly associated with the development of disability for older persons living in the community, regardless of their physical condition, according to a study in the November 3 issue of JAMA.

The authors provide as background information that while the prevalence of disability is decreasing, there are currently more than 7 million chronically disabled individuals aged 65 years or older in the United States. "Disability is associated with increased mortality and leads to additional adverse outcomes, such as nursing home placement and greater use of formal and informal home services, all of which place a substantial burden on older persons, informal caregivers, and health care resources. In the aggregate, the additional cost of medical and long-term care for newly disabled U.S. elderly individuals is estimated to be $26 billion per year."

Thomas M. Gill, M.D., and colleagues from Yale University School of Medicine, New Haven, Conn., assessed 754 people aged 70 years or older, who were not disabled (not requiring personal assistance) in four essential activities of daily living: bathing, dressing, walking inside the house, and transferring from a chair. Participants were categorized into 2 groups according to the presence of physical frailty and were followed up with monthly telephone interviews for up to 5 years to determine exposure to intervening events (illnesses or injuries) and the occurrence of disability.

"During the 5-year follow-up period, disability developed among 417 (55.3 percent) participants, 372 (49.3 percent) were hospitalized and 600 (79.6 percent) had at least one episode of restricted activity," the authors found. "...participants who developed disability were significantly more likely to have been hospitalized or to have had restricted activity than those who did not develop disability."

"In absolute terms, illnesses and injuries leading to hospitalization accounted for about 50 percent to 80 percent of the disability outcomes. Another 5 percent to 19 percent of the disability outcomes were attributable to illnesses and injuries leading to restricted activity but not to hospitalization. Depending on the specific disability outcome, the risk of disability was elevated more than 5-fold in the setting of restricted activity." The authors add that "falls and fall-related injuries resulting in hospitalization or restricted activity conferred the highest risk of disability..."

CHICAGO—The risk of treatment-related (toxic) death for cancer patients enrolled in phase 1 clinical trials had decreased significantly over the past 12 years (from 1991 to 2002), according to an article in the November 3 issue of JAMA.

This year, more than 550,000 Americans will die from cancer, and this number is expected to increase as the population ages, according to background information in the article. Efforts to develop new therapies have never been greater. There are more than 550 phase 1 trials open to cancer patients in the United States at any given time, and the numbers are steadily increasing as more products of the biotech industry reach the clinic. Phase 1 clinical trials represent the first testing of an investigational agent in humans. The major objectives during phase 1 are to characterize the agent's toxicity profile and to determine a dose and schedule appropriate for phase 2 testing. Patients who chose to participate may experience significant risks with limited chance to benefit.

Over the last decade, cancer drugs under development have become more targeted, and the clinical research environment has become more scrutinized. The impact of these changes on the risks and benefits to patients who participate in phase 1 cancer trials has been unknown.

Thomas G. Roberts, Jr., M.D., M.Soc.Sci., of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues conducted a study to determine if trends in the rates of objective response, treatment-related death, and serious toxicity in phase 1 cancer trials have changed over time. The authors searched abstracts and journal articles reporting the results of phase 1 cancer treatment trials originally submitted to annual meetings of the American Society of Clinical Oncology (ASCO) from 1991 through 2002.

The researchers found that the overall toxic death rate for 213 studies (involving 6,474 cancer patients) published in peer-reviewed journals was 0.54 percent, while the overall objective response rate was 3.8 percent. Toxic death rates decreased over the study period, from 1.1 percent over the first 4 years of the study (1991-1994) to 0.06 percent over the most recent 4-year period (1999-2002). Response rates also decreased, but by proportionally much less. After adjusting for characteristics of the experimental trials and the investigational agents, the odds of a patient dying from an experimental treatment while participating in a trial submitted during the most recent 4-year period were less than one-tenth those of a patient participating in a trial submitted during the first 4-year period. In comparison, the adjusted odds of a patient experiencing an objective response over the same time periods decreased by approximately half.

ANNUAL FLU REVACCINATION REDUCES RISK OF DEATH IN ELDERLY BY AT LEAST 24%