Jeff Evans

BETHESDA, MD. — High body mass index and high plasma glucose levels after an oral glucose challenge are independently associated with an increased risk of dying of hematopoietic cancer, Dr. Brian Chiu reported at the annual meeting of the American Society of Preventive Oncology.

In some instances, those two factors showed a strong, dose-response relationship in increasing the risk of dying of hematopoietic cancer, particularly non-Hodgkin lymphoma (NHL) or leukemia.

“We are particularly focusing on non-Hodgkin lymphoma because according to Surveillance, Epidemiology, and End Results (SEER) data, the incidence of non-Hodgkin lymphoma in the United States has been increasing dramatically during the past 30 years” from about 10 cases per 100,000 person-years in 1973 to 20 per 100,000 in 2002, said Dr. Chiu of the department of preventive medicine at Northwestern University, Chicago. The increase has occurred in both men and women.

The prevalence of obesity has also increased at the same time, rising by 60% from 1970 to1990 and by 74% from 1990 to 2002, according to data from the first three National Health and Nutrition Examination Surveys. The prevalence of diagnosed diabetes increased by about 60% during 1990–2004.

The current prospective study involved 35,420 people (average age 40 years) who participated in the Chicago Heart Association Detection Project in Industry during 1967–1973. The study was originally designed to screen for cardiovascular disease risk factors.

At baseline, participants' height and weight were assessed, as was blood glucose level 1 hour after they received an oral 50-g dose of glucose.

Dr. Chiu found that by the end of 2002, 129 study participants had died of NHL, 151 of leukemia, and 66 of multiple myeloma.

Men in the highest quartile of BMI (28.7 kg/m

Dr. Chiu collected data on participant mortality, but not on the prevalence of hematopoietic cancers at baseline. He excluded people who died of a hematopoietic cancer within the first 5 years of follow-up. Although this methodology might miss some hematopoietic cancer survivors, he suggested that the number of people with such cancers at baseline would be small because the cancers are rare and all of the subjects were in the work force during screening.

BETHESDA, MD. — High body mass index and high plasma glucose levels after an oral glucose challenge are independently associated with an increased risk of dying of hematopoietic cancer, Dr. Brian Chiu reported at the annual meeting of the American Society of Preventive Oncology.

In some instances, those two factors showed a strong, dose-response relationship in increasing the risk of dying of hematopoietic cancer, particularly non-Hodgkin lymphoma (NHL) or leukemia.

“We are particularly focusing on non-Hodgkin lymphoma because according to Surveillance, Epidemiology, and End Results (SEER) data, the incidence of non-Hodgkin lymphoma in the United States has been increasing dramatically during the past 30 years” from about 10 cases per 100,000 person-years in 1973 to 20 per 100,000 in 2002, said Dr. Chiu of the department of preventive medicine at Northwestern University, Chicago. The increase has occurred in both men and women.

The prevalence of obesity has also increased at the same time, rising by 60% from 1970 to1990 and by 74% from 1990 to 2002, according to data from the first three National Health and Nutrition Examination Surveys. The prevalence of diagnosed diabetes increased by about 60% during 1990–2004.

The current prospective study involved 35,420 people (average age 40 years) who participated in the Chicago Heart Association Detection Project in Industry during 1967–1973. The study was originally designed to screen for cardiovascular disease risk factors.

At baseline, participants' height and weight were assessed, as was blood glucose level 1 hour after they received an oral 50-g dose of glucose.

Dr. Chiu found that by the end of 2002, 129 study participants had died of NHL, 151 of leukemia, and 66 of multiple myeloma.

Men in the highest quartile of BMI (28.7 kg/m

Dr. Chiu collected data on participant mortality, but not on the prevalence of hematopoietic cancers at baseline. He excluded people who died of a hematopoietic cancer within the first 5 years of follow-up. Although this methodology might miss some hematopoietic cancer survivors, he suggested that the number of people with such cancers at baseline would be small because the cancers are rare and all of the subjects were in the work force during screening.

BETHESDA, MD. — High body mass index and high plasma glucose levels after an oral glucose challenge are independently associated with an increased risk of dying of hematopoietic cancer, Dr. Brian Chiu reported at the annual meeting of the American Society of Preventive Oncology.

In some instances, those two factors showed a strong, dose-response relationship in increasing the risk of dying of hematopoietic cancer, particularly non-Hodgkin lymphoma (NHL) or leukemia.

“We are particularly focusing on non-Hodgkin lymphoma because according to Surveillance, Epidemiology, and End Results (SEER) data, the incidence of non-Hodgkin lymphoma in the United States has been increasing dramatically during the past 30 years” from about 10 cases per 100,000 person-years in 1973 to 20 per 100,000 in 2002, said Dr. Chiu of the department of preventive medicine at Northwestern University, Chicago. The increase has occurred in both men and women.

The prevalence of obesity has also increased at the same time, rising by 60% from 1970 to1990 and by 74% from 1990 to 2002, according to data from the first three National Health and Nutrition Examination Surveys. The prevalence of diagnosed diabetes increased by about 60% during 1990–2004.

The current prospective study involved 35,420 people (average age 40 years) who participated in the Chicago Heart Association Detection Project in Industry during 1967–1973. The study was originally designed to screen for cardiovascular disease risk factors.

At baseline, participants' height and weight were assessed, as was blood glucose level 1 hour after they received an oral 50-g dose of glucose.

Dr. Chiu found that by the end of 2002, 129 study participants had died of NHL, 151 of leukemia, and 66 of multiple myeloma.

Men in the highest quartile of BMI (28.7 kg/m

Dr. Chiu collected data on participant mortality, but not on the prevalence of hematopoietic cancers at baseline. He excluded people who died of a hematopoietic cancer within the first 5 years of follow-up. Although this methodology might miss some hematopoietic cancer survivors, he suggested that the number of people with such cancers at baseline would be small because the cancers are rare and all of the subjects were in the work force during screening.

BETHESDA, MD. – Personnel dedicated to screen, conduct brief interventions, and refer patients for alcohol and drug problems and other risky behaviors can make an important addition to the emergency department, according to investigators at Yale-New Haven Hospital.

In the Yale-New Haven (Conn.) program, called Project ASSERT, “health promotion advocates” (HPAs) relieve ED practitioners such as nurses, physicians, and physician assistants from conducting time-intensive visits with alcohol or drug abusing patients.

“It took people a little bit of time to get used to [the HPAs] and know that they were there, but once they saw what was happening where they were able to do these referrals and get patients out of the emergency department to a treatment facility, they saw it as beneficial,” said Linda C. Degutis, Dr.P.H., codirector of Project ASSERT (program for improving Alcohol and Substance Abuse Services and Educating Providers to Refer Patients to Treatment.)

Project ASSERT has received so much support from ED staff and the New Haven community that the hospital now completely funds the program outside of any grants, Dr. Gail D'Onofrio said at the annual conference of the Association for Medical Education and Research in Substance Abuse. Project ASSERT is funded by HPA consultation fees that are included in the hospital's billing processes.

The HPAs appear to have had a substantial impact on the patients they see. As many as 87% of the patients who were referred by the HPAs to specialized treatment centers for alcohol or other drug problems during 1999–2004 actually enrolled in treatment programs, said Dr. D'Onofrio, codirector of Project ASSERT.

Reports have shown that patients who present to the ED are more likely to have substance abuse problems than are those who present in a primary care setting, and less than 1% of ED patients with a diagnosis of substance abuse actually report it in the ED, said Dr. D'Onofrio, of the emergency medicine department at Yale University, New Haven.

In most EDs, practitioners do not routinely screen for drug and alcohol problems in patients who are not acutely intoxicated or do not ask for detox. “If someone comes in with an ankle sprain, [ED staff] are not asking them about alcohol and other drugs,” Dr. Degutis said in an interview. “That's where HPAs will do some screening and identify things that aren't generally identified by the staff.”

Time constraints prevent screening every patient who comes through the ED, but ED practitioners know that patients with certain diagnoses are more likely to have a problem, such as those with trauma.

The HPAs' duties include screening patients for at-risk alcohol and substance use or dependence, providing brief early interventions, and then referring ED patients to treatment programs. They also screen for selected health problems, domestic violence, and depression.

The program uses an equivalent of 2.8 full-time employees from 7 a.m. to 11 p.m. weekdays, 7 a.m. to 7 p.m. Saturdays, and 7 a.m. to 3:30 p.m. Sundays. So far, only one of the advocates is fluent in Spanish.

“It's important to know that when you try to do something like this in any place, it's really the people you hire, not particularly all your expertise” that makes the program work, Dr. D'Onofrio said at the conference, which also was sponsored by Brown Medical School. HPAs at Yale-New Haven came from jobs in occupational therapy, the department of public health, and addiction services, where they showed that they can relate well and are motivated to do that, she said.

HPAs “are not necessarily people with extensive education and training–that's not the requirement,” Dr. Degutis said. “The requirement is more that they're familiar with the community, are interested in working with a range of people, are committed to working in the area of substance abuse, and have good interpersonal skills.”

Initially, HPAs screened all patients who were suspected of alcohol or drug use at the beginning of the program. After the program was more established, however, emergency practitioners screened some patients and sent them to the HPAs for brief interventions and referrals. HPAs still screen patients if they are not in the midst of taking care of patients who have been referred to them, said Dr. Degutis, associate professor of emergency medicine at the university.

The HPAs perform a brief, 10–15 minute intervention for anyone with a risky behavior and then refer to a variety of services in primary care, psychiatry, or social work. Alcohol use is gauged with the CAGE test and criteria from the National Institute on Alcohol Abuse and Alcoholism.

Of 22,923 patients screened for alcohol and other drug problems during December 1999 through December 2004, 10,255 (45%) reported using alcohol. Among the 5,243 patients who exceeded low-risk criteria set by the NIAAA, 43% (2,258) met the NIAAA criteria for at-risk or hazardous drinking or reported no more than one of the CAGE criteria. A total of 58% (3,085) were dependent on alcohol, based on meeting two or more CAGE criteria. About 15% of all the patients who were screened reported illicit drug use.

The HPAs performed brief interventions for 7,196 patients and referred 3,571 patients to specialized treatment facilities, mostly for problems with alcohol (59%), but also for drugs (28%) or both (13%).

At 1 month after presentation to the ED, the investigators were able to account for 74% of the referred patients either by talking with the patient directly on the phone or by calling the referred treatment facility. Of those who were contacted, 87% enrolled in a treatment program. Even if none of the patients who were not contacted enrolled in a treatment center, 64% of referred patients still enrolled in a treatment facility.

The Boston Medical Center ED, which originally started Project ASSERT as a demonstration project in 1993, runs a program similar to the one at Yale-New Haven. Several other hospitals around the country are trying to develop programs modeled after Project ASSERT.

One program is in its beginning stages at the Hospital of Saint Raphael, New Haven. So far the program has had some difficulty gaining support from ED staff at Saint Raphael, said Dr. Degutis. Unlike the HPAs at Yale-New Haven, the HPAs at Saint Raphael are not part of the ED staff. They are instead hired by the department of psychiatry at the hospital.

These HPAs have name badges with “psychiatry” printed on them, which “may change the way that the patient views them” when they go to ask a set of screening questions, Dr. Degutis explained. HPAs at Yale-New Haven have name badges printed with “Project ASSERT,” so that they can tell patients that they are part of a screening project to look for health risks.

BETHESDA, MD. – Personnel dedicated to screen, conduct brief interventions, and refer patients for alcohol and drug problems and other risky behaviors can make an important addition to the emergency department, according to investigators at Yale-New Haven Hospital.

In the Yale-New Haven (Conn.) program, called Project ASSERT, “health promotion advocates” (HPAs) relieve ED practitioners such as nurses, physicians, and physician assistants from conducting time-intensive visits with alcohol or drug abusing patients.

“It took people a little bit of time to get used to [the HPAs] and know that they were there, but once they saw what was happening where they were able to do these referrals and get patients out of the emergency department to a treatment facility, they saw it as beneficial,” said Linda C. Degutis, Dr.P.H., codirector of Project ASSERT (program for improving Alcohol and Substance Abuse Services and Educating Providers to Refer Patients to Treatment.)

Project ASSERT has received so much support from ED staff and the New Haven community that the hospital now completely funds the program outside of any grants, Dr. Gail D'Onofrio said at the annual conference of the Association for Medical Education and Research in Substance Abuse. Project ASSERT is funded by HPA consultation fees that are included in the hospital's billing processes.

The HPAs appear to have had a substantial impact on the patients they see. As many as 87% of the patients who were referred by the HPAs to specialized treatment centers for alcohol or other drug problems during 1999–2004 actually enrolled in treatment programs, said Dr. D'Onofrio, codirector of Project ASSERT.

Reports have shown that patients who present to the ED are more likely to have substance abuse problems than are those who present in a primary care setting, and less than 1% of ED patients with a diagnosis of substance abuse actually report it in the ED, said Dr. D'Onofrio, of the emergency medicine department at Yale University, New Haven.

In most EDs, practitioners do not routinely screen for drug and alcohol problems in patients who are not acutely intoxicated or do not ask for detox. “If someone comes in with an ankle sprain, [ED staff] are not asking them about alcohol and other drugs,” Dr. Degutis said in an interview. “That's where HPAs will do some screening and identify things that aren't generally identified by the staff.”

Time constraints prevent screening every patient who comes through the ED, but ED practitioners know that patients with certain diagnoses are more likely to have a problem, such as those with trauma.

The HPAs' duties include screening patients for at-risk alcohol and substance use or dependence, providing brief early interventions, and then referring ED patients to treatment programs. They also screen for selected health problems, domestic violence, and depression.

The program uses an equivalent of 2.8 full-time employees from 7 a.m. to 11 p.m. weekdays, 7 a.m. to 7 p.m. Saturdays, and 7 a.m. to 3:30 p.m. Sundays. So far, only one of the advocates is fluent in Spanish.

“It's important to know that when you try to do something like this in any place, it's really the people you hire, not particularly all your expertise” that makes the program work, Dr. D'Onofrio said at the conference, which also was sponsored by Brown Medical School. HPAs at Yale-New Haven came from jobs in occupational therapy, the department of public health, and addiction services, where they showed that they can relate well and are motivated to do that, she said.

HPAs “are not necessarily people with extensive education and training–that's not the requirement,” Dr. Degutis said. “The requirement is more that they're familiar with the community, are interested in working with a range of people, are committed to working in the area of substance abuse, and have good interpersonal skills.”

Initially, HPAs screened all patients who were suspected of alcohol or drug use at the beginning of the program. After the program was more established, however, emergency practitioners screened some patients and sent them to the HPAs for brief interventions and referrals. HPAs still screen patients if they are not in the midst of taking care of patients who have been referred to them, said Dr. Degutis, associate professor of emergency medicine at the university.

The HPAs perform a brief, 10–15 minute intervention for anyone with a risky behavior and then refer to a variety of services in primary care, psychiatry, or social work. Alcohol use is gauged with the CAGE test and criteria from the National Institute on Alcohol Abuse and Alcoholism.

Of 22,923 patients screened for alcohol and other drug problems during December 1999 through December 2004, 10,255 (45%) reported using alcohol. Among the 5,243 patients who exceeded low-risk criteria set by the NIAAA, 43% (2,258) met the NIAAA criteria for at-risk or hazardous drinking or reported no more than one of the CAGE criteria. A total of 58% (3,085) were dependent on alcohol, based on meeting two or more CAGE criteria. About 15% of all the patients who were screened reported illicit drug use.

The HPAs performed brief interventions for 7,196 patients and referred 3,571 patients to specialized treatment facilities, mostly for problems with alcohol (59%), but also for drugs (28%) or both (13%).

At 1 month after presentation to the ED, the investigators were able to account for 74% of the referred patients either by talking with the patient directly on the phone or by calling the referred treatment facility. Of those who were contacted, 87% enrolled in a treatment program. Even if none of the patients who were not contacted enrolled in a treatment center, 64% of referred patients still enrolled in a treatment facility.

The Boston Medical Center ED, which originally started Project ASSERT as a demonstration project in 1993, runs a program similar to the one at Yale-New Haven. Several other hospitals around the country are trying to develop programs modeled after Project ASSERT.

One program is in its beginning stages at the Hospital of Saint Raphael, New Haven. So far the program has had some difficulty gaining support from ED staff at Saint Raphael, said Dr. Degutis. Unlike the HPAs at Yale-New Haven, the HPAs at Saint Raphael are not part of the ED staff. They are instead hired by the department of psychiatry at the hospital.

These HPAs have name badges with “psychiatry” printed on them, which “may change the way that the patient views them” when they go to ask a set of screening questions, Dr. Degutis explained. HPAs at Yale-New Haven have name badges printed with “Project ASSERT,” so that they can tell patients that they are part of a screening project to look for health risks.

BETHESDA, MD. – Personnel dedicated to screen, conduct brief interventions, and refer patients for alcohol and drug problems and other risky behaviors can make an important addition to the emergency department, according to investigators at Yale-New Haven Hospital.

In the Yale-New Haven (Conn.) program, called Project ASSERT, “health promotion advocates” (HPAs) relieve ED practitioners such as nurses, physicians, and physician assistants from conducting time-intensive visits with alcohol or drug abusing patients.

“It took people a little bit of time to get used to [the HPAs] and know that they were there, but once they saw what was happening where they were able to do these referrals and get patients out of the emergency department to a treatment facility, they saw it as beneficial,” said Linda C. Degutis, Dr.P.H., codirector of Project ASSERT (program for improving Alcohol and Substance Abuse Services and Educating Providers to Refer Patients to Treatment.)

Project ASSERT has received so much support from ED staff and the New Haven community that the hospital now completely funds the program outside of any grants, Dr. Gail D'Onofrio said at the annual conference of the Association for Medical Education and Research in Substance Abuse. Project ASSERT is funded by HPA consultation fees that are included in the hospital's billing processes.

The HPAs appear to have had a substantial impact on the patients they see. As many as 87% of the patients who were referred by the HPAs to specialized treatment centers for alcohol or other drug problems during 1999–2004 actually enrolled in treatment programs, said Dr. D'Onofrio, codirector of Project ASSERT.

Reports have shown that patients who present to the ED are more likely to have substance abuse problems than are those who present in a primary care setting, and less than 1% of ED patients with a diagnosis of substance abuse actually report it in the ED, said Dr. D'Onofrio, of the emergency medicine department at Yale University, New Haven.

In most EDs, practitioners do not routinely screen for drug and alcohol problems in patients who are not acutely intoxicated or do not ask for detox. “If someone comes in with an ankle sprain, [ED staff] are not asking them about alcohol and other drugs,” Dr. Degutis said in an interview. “That's where HPAs will do some screening and identify things that aren't generally identified by the staff.”

Time constraints prevent screening every patient who comes through the ED, but ED practitioners know that patients with certain diagnoses are more likely to have a problem, such as those with trauma.

The HPAs' duties include screening patients for at-risk alcohol and substance use or dependence, providing brief early interventions, and then referring ED patients to treatment programs. They also screen for selected health problems, domestic violence, and depression.

The program uses an equivalent of 2.8 full-time employees from 7 a.m. to 11 p.m. weekdays, 7 a.m. to 7 p.m. Saturdays, and 7 a.m. to 3:30 p.m. Sundays. So far, only one of the advocates is fluent in Spanish.

“It's important to know that when you try to do something like this in any place, it's really the people you hire, not particularly all your expertise” that makes the program work, Dr. D'Onofrio said at the conference, which also was sponsored by Brown Medical School. HPAs at Yale-New Haven came from jobs in occupational therapy, the department of public health, and addiction services, where they showed that they can relate well and are motivated to do that, she said.

HPAs “are not necessarily people with extensive education and training–that's not the requirement,” Dr. Degutis said. “The requirement is more that they're familiar with the community, are interested in working with a range of people, are committed to working in the area of substance abuse, and have good interpersonal skills.”

Initially, HPAs screened all patients who were suspected of alcohol or drug use at the beginning of the program. After the program was more established, however, emergency practitioners screened some patients and sent them to the HPAs for brief interventions and referrals. HPAs still screen patients if they are not in the midst of taking care of patients who have been referred to them, said Dr. Degutis, associate professor of emergency medicine at the university.

The HPAs perform a brief, 10–15 minute intervention for anyone with a risky behavior and then refer to a variety of services in primary care, psychiatry, or social work. Alcohol use is gauged with the CAGE test and criteria from the National Institute on Alcohol Abuse and Alcoholism.

Of 22,923 patients screened for alcohol and other drug problems during December 1999 through December 2004, 10,255 (45%) reported using alcohol. Among the 5,243 patients who exceeded low-risk criteria set by the NIAAA, 43% (2,258) met the NIAAA criteria for at-risk or hazardous drinking or reported no more than one of the CAGE criteria. A total of 58% (3,085) were dependent on alcohol, based on meeting two or more CAGE criteria. About 15% of all the patients who were screened reported illicit drug use.

The HPAs performed brief interventions for 7,196 patients and referred 3,571 patients to specialized treatment facilities, mostly for problems with alcohol (59%), but also for drugs (28%) or both (13%).

At 1 month after presentation to the ED, the investigators were able to account for 74% of the referred patients either by talking with the patient directly on the phone or by calling the referred treatment facility. Of those who were contacted, 87% enrolled in a treatment program. Even if none of the patients who were not contacted enrolled in a treatment center, 64% of referred patients still enrolled in a treatment facility.

The Boston Medical Center ED, which originally started Project ASSERT as a demonstration project in 1993, runs a program similar to the one at Yale-New Haven. Several other hospitals around the country are trying to develop programs modeled after Project ASSERT.

One program is in its beginning stages at the Hospital of Saint Raphael, New Haven. So far the program has had some difficulty gaining support from ED staff at Saint Raphael, said Dr. Degutis. Unlike the HPAs at Yale-New Haven, the HPAs at Saint Raphael are not part of the ED staff. They are instead hired by the department of psychiatry at the hospital.

These HPAs have name badges with “psychiatry” printed on them, which “may change the way that the patient views them” when they go to ask a set of screening questions, Dr. Degutis explained. HPAs at Yale-New Haven have name badges printed with “Project ASSERT,” so that they can tell patients that they are part of a screening project to look for health risks.

STOCKHOLM – Interventions aimed at preventing suicide in older adults should target asymptomatic individuals and groups at risk for becoming depressed and suicidal to save the greatest number of lives, Dr. Yeates Conwell said at the 12th Congress of the International Psychogeriatric Association.

“There has been a tremendous amount of progress in recent years, largely from case-controlled, psychological autopsy studies, which have revealed an evidence base that I think provides a firm foundation for us to design preventive interventions,” said Dr. Conwell of the Center for the Study and Prevention of Suicide at the University of Rochester (N.Y.).

Preventive interventions could be created to match trajectories toward suicide that some individuals experience as they age. Strategies could be tailored to address the particular mix of personality strengths and weaknesses, social contexts, and cultural values of a person or group.

Early intervention could be appropriate in selected individuals who, as they age, begin to develop rigid responses to stress that trigger symptoms and then develop into syndromes of depression and hopelessness.

Preventive interventions could be indicated in the people who drop into a perisuicidal state, Dr. Conwell said.

Some of the risk factors for suicide that have been identified in older adults include psychiatric illness (especially depression), prior suicide attempts, comorbid medical conditions, social dependence and isolation, family discord, personal losses, inflexible coping skills, and access to a means to commit suicide.

About 1 in 30 suicide attempts made by people in the general population is completed. But among the elderly, this proportion increases to 1 in 4.

The rate of completion is greater among the elderly than among younger people because older adults are more frail and isolated, and they tend to be more deliberate and make plans about their self-destructive act. About 75% of older adults who attempt suicide do so with a firearm, compared with about 50% for all suicide attempters combined, Dr. Conwell noted.

These factors imply that “the interventions that we mount to prevent suicide in older adulthood have to be very aggressive but also suggest that we need to push preventive interventions” away from the suicidal crisis toward the realms of secondary and primary prevention, he said.

The primary care setting is an important place to intervene, given that many studies have shown that about 70%–75% of older people who have committed suicide saw a primary care provider in the month before the attempt; one-third to one-half of suicide completers had seen a primary care provider in the week before, he said. Mental health centers do not seem to be the place to intervene, since older adults are found at such centers in much lower proportions than younger adults.

Potential places to intervene outside of the medical setting include long-term care facilities, home health care agencies, and aging services providers. The highest number of lives may be saved by prioritizing intervention resources to four of nine possible ways of addressing suicide in older adults, Dr. Conwell said:

▸ In high-risk people who show no symptoms, depression could be screened for and treated by primary care providers in an office-based setting or by social services or home health care providers in the community. The Prevention of Suicide in Primary Care Elderly: Collaborative Trial (PROSPECT) study used this design to detect and treat depression in primary care.

▸ To target high-risk but asymptomatic, groups of patients who may be socially isolated, in pain, or low functioning, geriatric physicians could assess and address problems to improve social and functional limitations. Good home health care and social outreach programs could maintain independence at home and reduce social isolation, he said.

▸ In order for preventive interventions to reach everyone, the entire population would have to be educated about normal aging and the fact that older age does not need to be “a negative time of life,” Dr. Conwell explained. Access to care and social services would need to be increased for all older adults through legislative means and social engineering, according to Dr. Conwell.

▸ Universal outreach to the entire population to help those who are depressed would entail reducing the stigma associated with receiving mental health care and restricting access to lethal means, such as firearms.

STOCKHOLM – Interventions aimed at preventing suicide in older adults should target asymptomatic individuals and groups at risk for becoming depressed and suicidal to save the greatest number of lives, Dr. Yeates Conwell said at the 12th Congress of the International Psychogeriatric Association.

“There has been a tremendous amount of progress in recent years, largely from case-controlled, psychological autopsy studies, which have revealed an evidence base that I think provides a firm foundation for us to design preventive interventions,” said Dr. Conwell of the Center for the Study and Prevention of Suicide at the University of Rochester (N.Y.).

Preventive interventions could be created to match trajectories toward suicide that some individuals experience as they age. Strategies could be tailored to address the particular mix of personality strengths and weaknesses, social contexts, and cultural values of a person or group.

Early intervention could be appropriate in selected individuals who, as they age, begin to develop rigid responses to stress that trigger symptoms and then develop into syndromes of depression and hopelessness.

Preventive interventions could be indicated in the people who drop into a perisuicidal state, Dr. Conwell said.

Some of the risk factors for suicide that have been identified in older adults include psychiatric illness (especially depression), prior suicide attempts, comorbid medical conditions, social dependence and isolation, family discord, personal losses, inflexible coping skills, and access to a means to commit suicide.

About 1 in 30 suicide attempts made by people in the general population is completed. But among the elderly, this proportion increases to 1 in 4.

The rate of completion is greater among the elderly than among younger people because older adults are more frail and isolated, and they tend to be more deliberate and make plans about their self-destructive act. About 75% of older adults who attempt suicide do so with a firearm, compared with about 50% for all suicide attempters combined, Dr. Conwell noted.

These factors imply that “the interventions that we mount to prevent suicide in older adulthood have to be very aggressive but also suggest that we need to push preventive interventions” away from the suicidal crisis toward the realms of secondary and primary prevention, he said.

The primary care setting is an important place to intervene, given that many studies have shown that about 70%–75% of older people who have committed suicide saw a primary care provider in the month before the attempt; one-third to one-half of suicide completers had seen a primary care provider in the week before, he said. Mental health centers do not seem to be the place to intervene, since older adults are found at such centers in much lower proportions than younger adults.

Potential places to intervene outside of the medical setting include long-term care facilities, home health care agencies, and aging services providers. The highest number of lives may be saved by prioritizing intervention resources to four of nine possible ways of addressing suicide in older adults, Dr. Conwell said:

▸ In high-risk people who show no symptoms, depression could be screened for and treated by primary care providers in an office-based setting or by social services or home health care providers in the community. The Prevention of Suicide in Primary Care Elderly: Collaborative Trial (PROSPECT) study used this design to detect and treat depression in primary care.

▸ To target high-risk but asymptomatic, groups of patients who may be socially isolated, in pain, or low functioning, geriatric physicians could assess and address problems to improve social and functional limitations. Good home health care and social outreach programs could maintain independence at home and reduce social isolation, he said.

▸ In order for preventive interventions to reach everyone, the entire population would have to be educated about normal aging and the fact that older age does not need to be “a negative time of life,” Dr. Conwell explained. Access to care and social services would need to be increased for all older adults through legislative means and social engineering, according to Dr. Conwell.

▸ Universal outreach to the entire population to help those who are depressed would entail reducing the stigma associated with receiving mental health care and restricting access to lethal means, such as firearms.

STOCKHOLM – Interventions aimed at preventing suicide in older adults should target asymptomatic individuals and groups at risk for becoming depressed and suicidal to save the greatest number of lives, Dr. Yeates Conwell said at the 12th Congress of the International Psychogeriatric Association.

“There has been a tremendous amount of progress in recent years, largely from case-controlled, psychological autopsy studies, which have revealed an evidence base that I think provides a firm foundation for us to design preventive interventions,” said Dr. Conwell of the Center for the Study and Prevention of Suicide at the University of Rochester (N.Y.).

Preventive interventions could be created to match trajectories toward suicide that some individuals experience as they age. Strategies could be tailored to address the particular mix of personality strengths and weaknesses, social contexts, and cultural values of a person or group.

Early intervention could be appropriate in selected individuals who, as they age, begin to develop rigid responses to stress that trigger symptoms and then develop into syndromes of depression and hopelessness.

Preventive interventions could be indicated in the people who drop into a perisuicidal state, Dr. Conwell said.

Some of the risk factors for suicide that have been identified in older adults include psychiatric illness (especially depression), prior suicide attempts, comorbid medical conditions, social dependence and isolation, family discord, personal losses, inflexible coping skills, and access to a means to commit suicide.

About 1 in 30 suicide attempts made by people in the general population is completed. But among the elderly, this proportion increases to 1 in 4.

The rate of completion is greater among the elderly than among younger people because older adults are more frail and isolated, and they tend to be more deliberate and make plans about their self-destructive act. About 75% of older adults who attempt suicide do so with a firearm, compared with about 50% for all suicide attempters combined, Dr. Conwell noted.

These factors imply that “the interventions that we mount to prevent suicide in older adulthood have to be very aggressive but also suggest that we need to push preventive interventions” away from the suicidal crisis toward the realms of secondary and primary prevention, he said.

The primary care setting is an important place to intervene, given that many studies have shown that about 70%–75% of older people who have committed suicide saw a primary care provider in the month before the attempt; one-third to one-half of suicide completers had seen a primary care provider in the week before, he said. Mental health centers do not seem to be the place to intervene, since older adults are found at such centers in much lower proportions than younger adults.

Potential places to intervene outside of the medical setting include long-term care facilities, home health care agencies, and aging services providers. The highest number of lives may be saved by prioritizing intervention resources to four of nine possible ways of addressing suicide in older adults, Dr. Conwell said:

▸ In high-risk people who show no symptoms, depression could be screened for and treated by primary care providers in an office-based setting or by social services or home health care providers in the community. The Prevention of Suicide in Primary Care Elderly: Collaborative Trial (PROSPECT) study used this design to detect and treat depression in primary care.

▸ To target high-risk but asymptomatic, groups of patients who may be socially isolated, in pain, or low functioning, geriatric physicians could assess and address problems to improve social and functional limitations. Good home health care and social outreach programs could maintain independence at home and reduce social isolation, he said.

▸ In order for preventive interventions to reach everyone, the entire population would have to be educated about normal aging and the fact that older age does not need to be “a negative time of life,” Dr. Conwell explained. Access to care and social services would need to be increased for all older adults through legislative means and social engineering, according to Dr. Conwell.

▸ Universal outreach to the entire population to help those who are depressed would entail reducing the stigma associated with receiving mental health care and restricting access to lethal means, such as firearms.

NEW YORK – Sparse evidence from double-blind, placebo-controlled trials backs the effectiveness of treatments for acute mania in children and adolescents with bipolar I disorder, but results from ongoing trials should be available soon, Dr. Gabrielle A. Carlson said at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.

Double-blind, placebo-controlled trials have been conducted with olanzapine (Zyprexa), topiramate (Topamax), and oxcarbazepine (Trileptal) for the treatment of acute mania in children and adolescents, but other drug trials are yet to be completed, said Dr. Carlson, director of child and adolescent psychiatry at the State University of New York at Stony Brook.

Trials of that nature are underway for divalproex (Depakote) and the atypical antipsychotics risperidone (Risperdal), quetiapine (Seroquel), ziprasidone (Geodon), and aripiprazole (Abilify).

No trials have been planned for lithium or clozapine (Clozaril).

Based on the primary end point of the amount of change in the Young Mania Rating Scale (YMRS) from baseline, only olanzapine has shown statistically significant efficacy, in comparison with placebo. Topiramate and oxcarbazepine have not reached statistical significance on this end point in a double-blind, placebo-controlled trial, she said.

In the olanzapine trial of patients aged 13–17 years, 49% of the 107 adolescents who received active treatment had greater than 50% improvement in their YMRS score, compared with 22% of the 54 patients who received placebo.

The rate of remission at the end of 3 weeks of treatment also was significantly higher for olanzapine (35%) than for placebo patients (11%).

The oxcarbazepine trial of 116 children and adolescents appeared to show some efficacy of the anticonvulsant in patients aged 7–12 years, because YMRS scores improved by greater than 50% in significantly more patients in that age group who received oxcarbazepine (41%) than in those who received placebo (17%).

Adolescents aged 13–18 years did not differ significantly in their response to carbamazepine (43%) or placebo (40%).

In the topiramate trial, mean YMRS scores improved from 31.7 to 22 for the 29 patients who received the anticonvulsant and from 29.9 to 25.2 for the 27 patients who received placebo.

The topiramate study was stopped early because the separate adult trials that involved topiramate failed to show efficacy for acute mania (J. Am. Acad. Child Adolesc. Psychiatry 2005;44:539–47).

In the topiramate and olanzapine trials, the clinician-rated scale of Clinical Global Impressions showed a statistically significant difference in the percentage of patients who were improved or very much improved.

In a head-to-head, double-blind, randomized trial of 50 patients, divalproex and quetiapine appeared to have similar efficacy in treating acute mania in hospitalized adolescents.

YMRS scores at baseline improved from an average of about 35 in each group to 17 in divalproex patients and to 13 in quetiapine patients.

“There wasn't a [significant] difference, because both of them work,” Dr. Carlson said.

No double-blind, placebo-controlled trials of lithium in children and adolescents for acute mania have been conducted, even though the drug has been used openly in adults and kids since the 1950s.

Most of the open-label, discontinuation, and/or add-on trials of lithium, divalproex, and carbamazepine have shown positive results for the treatment of acute mania in children and adolescents.

Similar results have been reported with risperidone, olanzapine, and quetiapine.

Polypharmacy studies in which a drug is added to augment the effects of another medication appear to be beneficial in patients who are able to tolerate the combination, Dr. Carlson said.

In one randomized, double-blind study of 30 patients, a combination of divalproex and quetiapine resulted in a significantly higher response rate (87%) than did divalproex plus placebo (53%), she noted.

Patients who took the combination also had significantly greater improvement on mean YMRS scores from baseline to 42 days (from 34 to 10 vs. from 31 to 17) (J. Am. Acad. Child Adolesc. Psychiatry 2002;41:1216–23).

The combination of divalproex and lithium also appears effective when tolerated.

An open-label study of this combination showed that 42 of 90 children and adolescents with mostly bipolar I disorder met stringent criteria for remission after an average of 13 weeks of treatment.

The 90 patients had an average YMRS score of 22 at baseline; this score improved to a mean of less than 1 in the patients who remitted (J. Am. Acad. Child Adolesc. Psychiatry 2003;42:895–901).

NEW YORK – Sparse evidence from double-blind, placebo-controlled trials backs the effectiveness of treatments for acute mania in children and adolescents with bipolar I disorder, but results from ongoing trials should be available soon, Dr. Gabrielle A. Carlson said at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.

Double-blind, placebo-controlled trials have been conducted with olanzapine (Zyprexa), topiramate (Topamax), and oxcarbazepine (Trileptal) for the treatment of acute mania in children and adolescents, but other drug trials are yet to be completed, said Dr. Carlson, director of child and adolescent psychiatry at the State University of New York at Stony Brook.

Trials of that nature are underway for divalproex (Depakote) and the atypical antipsychotics risperidone (Risperdal), quetiapine (Seroquel), ziprasidone (Geodon), and aripiprazole (Abilify).

No trials have been planned for lithium or clozapine (Clozaril).

Based on the primary end point of the amount of change in the Young Mania Rating Scale (YMRS) from baseline, only olanzapine has shown statistically significant efficacy, in comparison with placebo. Topiramate and oxcarbazepine have not reached statistical significance on this end point in a double-blind, placebo-controlled trial, she said.

In the olanzapine trial of patients aged 13–17 years, 49% of the 107 adolescents who received active treatment had greater than 50% improvement in their YMRS score, compared with 22% of the 54 patients who received placebo.

The rate of remission at the end of 3 weeks of treatment also was significantly higher for olanzapine (35%) than for placebo patients (11%).

The oxcarbazepine trial of 116 children and adolescents appeared to show some efficacy of the anticonvulsant in patients aged 7–12 years, because YMRS scores improved by greater than 50% in significantly more patients in that age group who received oxcarbazepine (41%) than in those who received placebo (17%).

Adolescents aged 13–18 years did not differ significantly in their response to carbamazepine (43%) or placebo (40%).

In the topiramate trial, mean YMRS scores improved from 31.7 to 22 for the 29 patients who received the anticonvulsant and from 29.9 to 25.2 for the 27 patients who received placebo.

The topiramate study was stopped early because the separate adult trials that involved topiramate failed to show efficacy for acute mania (J. Am. Acad. Child Adolesc. Psychiatry 2005;44:539–47).

In the topiramate and olanzapine trials, the clinician-rated scale of Clinical Global Impressions showed a statistically significant difference in the percentage of patients who were improved or very much improved.

In a head-to-head, double-blind, randomized trial of 50 patients, divalproex and quetiapine appeared to have similar efficacy in treating acute mania in hospitalized adolescents.

YMRS scores at baseline improved from an average of about 35 in each group to 17 in divalproex patients and to 13 in quetiapine patients.

“There wasn't a [significant] difference, because both of them work,” Dr. Carlson said.

No double-blind, placebo-controlled trials of lithium in children and adolescents for acute mania have been conducted, even though the drug has been used openly in adults and kids since the 1950s.

Most of the open-label, discontinuation, and/or add-on trials of lithium, divalproex, and carbamazepine have shown positive results for the treatment of acute mania in children and adolescents.

Similar results have been reported with risperidone, olanzapine, and quetiapine.

Polypharmacy studies in which a drug is added to augment the effects of another medication appear to be beneficial in patients who are able to tolerate the combination, Dr. Carlson said.

In one randomized, double-blind study of 30 patients, a combination of divalproex and quetiapine resulted in a significantly higher response rate (87%) than did divalproex plus placebo (53%), she noted.

Patients who took the combination also had significantly greater improvement on mean YMRS scores from baseline to 42 days (from 34 to 10 vs. from 31 to 17) (J. Am. Acad. Child Adolesc. Psychiatry 2002;41:1216–23).

The combination of divalproex and lithium also appears effective when tolerated.

An open-label study of this combination showed that 42 of 90 children and adolescents with mostly bipolar I disorder met stringent criteria for remission after an average of 13 weeks of treatment.

The 90 patients had an average YMRS score of 22 at baseline; this score improved to a mean of less than 1 in the patients who remitted (J. Am. Acad. Child Adolesc. Psychiatry 2003;42:895–901).

NEW YORK – Sparse evidence from double-blind, placebo-controlled trials backs the effectiveness of treatments for acute mania in children and adolescents with bipolar I disorder, but results from ongoing trials should be available soon, Dr. Gabrielle A. Carlson said at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.

Double-blind, placebo-controlled trials have been conducted with olanzapine (Zyprexa), topiramate (Topamax), and oxcarbazepine (Trileptal) for the treatment of acute mania in children and adolescents, but other drug trials are yet to be completed, said Dr. Carlson, director of child and adolescent psychiatry at the State University of New York at Stony Brook.

Trials of that nature are underway for divalproex (Depakote) and the atypical antipsychotics risperidone (Risperdal), quetiapine (Seroquel), ziprasidone (Geodon), and aripiprazole (Abilify).

No trials have been planned for lithium or clozapine (Clozaril).

Based on the primary end point of the amount of change in the Young Mania Rating Scale (YMRS) from baseline, only olanzapine has shown statistically significant efficacy, in comparison with placebo. Topiramate and oxcarbazepine have not reached statistical significance on this end point in a double-blind, placebo-controlled trial, she said.

In the olanzapine trial of patients aged 13–17 years, 49% of the 107 adolescents who received active treatment had greater than 50% improvement in their YMRS score, compared with 22% of the 54 patients who received placebo.

The rate of remission at the end of 3 weeks of treatment also was significantly higher for olanzapine (35%) than for placebo patients (11%).

The oxcarbazepine trial of 116 children and adolescents appeared to show some efficacy of the anticonvulsant in patients aged 7–12 years, because YMRS scores improved by greater than 50% in significantly more patients in that age group who received oxcarbazepine (41%) than in those who received placebo (17%).

Adolescents aged 13–18 years did not differ significantly in their response to carbamazepine (43%) or placebo (40%).

In the topiramate trial, mean YMRS scores improved from 31.7 to 22 for the 29 patients who received the anticonvulsant and from 29.9 to 25.2 for the 27 patients who received placebo.

The topiramate study was stopped early because the separate adult trials that involved topiramate failed to show efficacy for acute mania (J. Am. Acad. Child Adolesc. Psychiatry 2005;44:539–47).

In the topiramate and olanzapine trials, the clinician-rated scale of Clinical Global Impressions showed a statistically significant difference in the percentage of patients who were improved or very much improved.

In a head-to-head, double-blind, randomized trial of 50 patients, divalproex and quetiapine appeared to have similar efficacy in treating acute mania in hospitalized adolescents.

YMRS scores at baseline improved from an average of about 35 in each group to 17 in divalproex patients and to 13 in quetiapine patients.

“There wasn't a [significant] difference, because both of them work,” Dr. Carlson said.

No double-blind, placebo-controlled trials of lithium in children and adolescents for acute mania have been conducted, even though the drug has been used openly in adults and kids since the 1950s.

Most of the open-label, discontinuation, and/or add-on trials of lithium, divalproex, and carbamazepine have shown positive results for the treatment of acute mania in children and adolescents.

Similar results have been reported with risperidone, olanzapine, and quetiapine.

Polypharmacy studies in which a drug is added to augment the effects of another medication appear to be beneficial in patients who are able to tolerate the combination, Dr. Carlson said.

In one randomized, double-blind study of 30 patients, a combination of divalproex and quetiapine resulted in a significantly higher response rate (87%) than did divalproex plus placebo (53%), she noted.

Patients who took the combination also had significantly greater improvement on mean YMRS scores from baseline to 42 days (from 34 to 10 vs. from 31 to 17) (J. Am. Acad. Child Adolesc. Psychiatry 2002;41:1216–23).

The combination of divalproex and lithium also appears effective when tolerated.

An open-label study of this combination showed that 42 of 90 children and adolescents with mostly bipolar I disorder met stringent criteria for remission after an average of 13 weeks of treatment.

The 90 patients had an average YMRS score of 22 at baseline; this score improved to a mean of less than 1 in the patients who remitted (J. Am. Acad. Child Adolesc. Psychiatry 2003;42:895–901).

NEW YORK – Because of the current lack of data and consensus on the treatment of bipolar depression in children and adolescents, pharmacotherapeutic options need to be discussed with family members on a case-by-case basis, Dr. Gabrielle A. Carlson said at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.

No controlled studies of bipolar depression in children or adolescents exist and no results from such trials can be expected for the foreseeable future, said Dr. Carlson, director of child and adolescent psychiatry at the State University of New York at Stony Brook. A few recent open-label trials with lithium and lamotrigine (Lamictal) provide all the data that are available on pharmacotherapy in these patients.

In one study, a 6-week open trial of lithium in hospitalized adolescents with bipolar depression, 13 of the 27 patients had a 50% reduction in Children's Depression Rating Scale-Revised (CDRS-R) scores at some point during the study. At the end of the 6 weeks, however, only 8 patients met the study's response criteria, defined as a CDRS-R score of 28 or less and a Clinical Global Impressions (CGI) score of 2 or less. Most of the patients' improvement occurred during the first 2 weeks of the trial, when they were in the hospital.

In an open study of 20 adolescents with bipolar I, II, or depression not otherwise specified, 16 patients responded to lamotrigine after 8 weeks, as defined by a CGI score of 2 or less. Eleven patients were in remission after 8 weeks. Seven of the patients also were taking other psychotropic medications.

“Until there are placebo-controlled trials [of children and adolescents] in bipolar depression, don't get too excited because we all know that there are high rates of placebo response in depression,” Dr. Carlson said.

When treating a first-episode case of depression, clinicians should consider that bipolar disorder is prevalent in only 5% of children and adolescents who have a parent with the condition, according to one study, whereas unipolar depression and other affective disorders are prevalent in 9% and 27% of children and adolescents with such parents, respectively, she said.

Clinicians will need to consider different scenarios when treating a first episode of major depression in adolescents and children with bipolar disorder, or even recurrent unipolar major depression in pediatric patients with a history of bipolar disorder in their families. In both cases, the clinician will have to decide on whether to prescribe an antidepressant–which requires a discussion of its risks and benefits in light of the black box warning on suicidal ideation–or a mood stabilizer that may not be needed, Dr. Carlson said.

NEW YORK – Because of the current lack of data and consensus on the treatment of bipolar depression in children and adolescents, pharmacotherapeutic options need to be discussed with family members on a case-by-case basis, Dr. Gabrielle A. Carlson said at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.

No controlled studies of bipolar depression in children or adolescents exist and no results from such trials can be expected for the foreseeable future, said Dr. Carlson, director of child and adolescent psychiatry at the State University of New York at Stony Brook. A few recent open-label trials with lithium and lamotrigine (Lamictal) provide all the data that are available on pharmacotherapy in these patients.

In one study, a 6-week open trial of lithium in hospitalized adolescents with bipolar depression, 13 of the 27 patients had a 50% reduction in Children's Depression Rating Scale-Revised (CDRS-R) scores at some point during the study. At the end of the 6 weeks, however, only 8 patients met the study's response criteria, defined as a CDRS-R score of 28 or less and a Clinical Global Impressions (CGI) score of 2 or less. Most of the patients' improvement occurred during the first 2 weeks of the trial, when they were in the hospital.

In an open study of 20 adolescents with bipolar I, II, or depression not otherwise specified, 16 patients responded to lamotrigine after 8 weeks, as defined by a CGI score of 2 or less. Eleven patients were in remission after 8 weeks. Seven of the patients also were taking other psychotropic medications.

“Until there are placebo-controlled trials [of children and adolescents] in bipolar depression, don't get too excited because we all know that there are high rates of placebo response in depression,” Dr. Carlson said.

When treating a first-episode case of depression, clinicians should consider that bipolar disorder is prevalent in only 5% of children and adolescents who have a parent with the condition, according to one study, whereas unipolar depression and other affective disorders are prevalent in 9% and 27% of children and adolescents with such parents, respectively, she said.

Clinicians will need to consider different scenarios when treating a first episode of major depression in adolescents and children with bipolar disorder, or even recurrent unipolar major depression in pediatric patients with a history of bipolar disorder in their families. In both cases, the clinician will have to decide on whether to prescribe an antidepressant–which requires a discussion of its risks and benefits in light of the black box warning on suicidal ideation–or a mood stabilizer that may not be needed, Dr. Carlson said.

NEW YORK – Because of the current lack of data and consensus on the treatment of bipolar depression in children and adolescents, pharmacotherapeutic options need to be discussed with family members on a case-by-case basis, Dr. Gabrielle A. Carlson said at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.

No controlled studies of bipolar depression in children or adolescents exist and no results from such trials can be expected for the foreseeable future, said Dr. Carlson, director of child and adolescent psychiatry at the State University of New York at Stony Brook. A few recent open-label trials with lithium and lamotrigine (Lamictal) provide all the data that are available on pharmacotherapy in these patients.

In one study, a 6-week open trial of lithium in hospitalized adolescents with bipolar depression, 13 of the 27 patients had a 50% reduction in Children's Depression Rating Scale-Revised (CDRS-R) scores at some point during the study. At the end of the 6 weeks, however, only 8 patients met the study's response criteria, defined as a CDRS-R score of 28 or less and a Clinical Global Impressions (CGI) score of 2 or less. Most of the patients' improvement occurred during the first 2 weeks of the trial, when they were in the hospital.

In an open study of 20 adolescents with bipolar I, II, or depression not otherwise specified, 16 patients responded to lamotrigine after 8 weeks, as defined by a CGI score of 2 or less. Eleven patients were in remission after 8 weeks. Seven of the patients also were taking other psychotropic medications.

“Until there are placebo-controlled trials [of children and adolescents] in bipolar depression, don't get too excited because we all know that there are high rates of placebo response in depression,” Dr. Carlson said.

When treating a first-episode case of depression, clinicians should consider that bipolar disorder is prevalent in only 5% of children and adolescents who have a parent with the condition, according to one study, whereas unipolar depression and other affective disorders are prevalent in 9% and 27% of children and adolescents with such parents, respectively, she said.

Clinicians will need to consider different scenarios when treating a first episode of major depression in adolescents and children with bipolar disorder, or even recurrent unipolar major depression in pediatric patients with a history of bipolar disorder in their families. In both cases, the clinician will have to decide on whether to prescribe an antidepressant–which requires a discussion of its risks and benefits in light of the black box warning on suicidal ideation–or a mood stabilizer that may not be needed, Dr. Carlson said.

NEW YORK — The body of data for using newer pharmacotherapeutic agents to treat autistic symptoms is struggling to keep up with the use of such drugs in practice, Lawrence Scahill, Ph.D., said at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.

“An evidence-based discussion of autism is relatively brief, because we don't have a lot of evidence, unfortunately,” said Dr. Scahill, director of the research unit on pediatric psychopharmacology at the Yale Child Study Center, New Haven, Conn.

Some medications have proven to be useful in treating target symptoms of autism, such as hyperactivity, tantrums, aggression, self-injury, and anxiety, he said.

In a survey of medication patterns in patients with autism or pervasive developmental disorder (PDD) in North Carolina, the use of any medication to treat the conditions rose from 31% in 1992–1993 to 45% in 2001, Dr. Scahill noted (J. Child Adolesc. Psychopharmacol. 2005;15:116–26).

The use of several classes of drugs rose during that period, including antipsychotics (from 12% to 17%), antidepressants (from 6% to 21%), and stimulants (from 7% to 14%). For antipsychotics and antidepressants, these changes reflect switches to atypicals and SSRIs, said Dr. Scahill, who disclosed that he serves as a consultant for Janssen Pharmaceutica N.V., which manufactures risperidone (Risperdal), and Pfizer Inc., which manufactures fluoxetine.

SSRIs for Repetitive Behavior, Anxiety

SSRIs such as fluoxetine have been used in PDD to treat repetitive behavior, anxiety, and aggression, as well as to improve socialization, Dr. Scahill said.

Liquid fluoxetine proved to be more effective in treating repetitive behaviors than placebo in a randomized, double-blind, crossover study of 39 children and adolescents with autistic spectrum disorders. In the first phase of the trial, patients who received fluoxetine improved their scores on a clinician-rated instrument focused on repetitive behavior (the Children's Yale-Brown Obsessive Compulsive Scale-PDD) by 10%, compared with placebo patients who improved by 4%. The second phase of the study, in which the patients switched treatments, yielded similar results.

Adverse events occurred at a rate similar to that of placebo. The average dose of fluoxetine was 10 mg/day, beginning with 2.5 mg/day for the first week. “In terms of benefit, if you're aiming [SSRIs] at repetitive behavior, I don't say 'Don't do it,' but don't expect big effects,” he said.

Aggression, Tantrums, Self-Injury

Risperidone is the atypical antipsychotic that has been studied most extensively in PDD, with open and controlled trials involving a total of 223 patients.

The FDA previously declared risperidone as nonapprovable for the treatment of autism in children, but it is now being submitted for approval for the treatment of tantrums, aggression, and self-injury, Dr. Scahill said.

In an 8-week, randomized, double-blind trial, risperidone significantly reduced aggressive behavior, tantrums, and self-injurious behavior by 57% in 49 children, compared with 14% in 52 children on placebo, according to the parent-rated irritability subscale of the Aberrant Behavior Checklist. Clinician ratings yielded similar results. The patients averaged 1.8 mg/day (N. Engl. J. Med. 2002;347:314–21).

During a 4-month open-label extension of the study for 63 responders to risperidone, irritability scores did not worsen, and patients did not require more risperidone to maintain their response (Am. J. Psychiatry 2005;162:1361–9). These responders gained an average of 5.6 kg during a total of 6 months of treatment with risperidone (Am. J. Psychiatry 2004;161:1125–7).

In a 2-month, randomized, double-blind discontinuation of risperidone, patients who continued to receive risperidone had a significantly lower rate of relapse (2 of 16) than those who gradually replaced risperidone with placebo (10 of 16).

ADHD Symptoms

Even though hyperactivity is a common problem in children and adolescents with PDD, “the evidence to support the use of methylphenidate in this population is frightfully little,” Dr. Scahill said.

Until recently, methylphenidate had been studied in only two investigations of 10 children with PDD and ADHD. On the Conners Hyperactivity Index, teachers reported an 11% improvement at a dose of 10–20 mg twice daily (J. Autism Dev. Disord. 1995;25:283–94), 32% improvement at 0.3 mg/kg per dose, and 47% improvement at 0.6 mg/kg per dose (J. Am. Acad. Child Adolesc. Psychiatry 1999;38:805–12).

In a more rigorous study of 66 children with PDD and hyperactivity conducted by Dr. Scahill and his colleagues, methylphenidate improved hyperactivity significantly but less than it would in typically developing children with ADHD, according to teacher and parent ratings (Arch. Gen. Psychiatry 2005;62:1266–74). Children in the randomized, double-blind, crossover trial tolerated three dose levels of the drug in a 7-day test dose period and then received placebo for 1 week, followed by 3 weeks of the three methylphenidate doses in random order.

Thirty-four patients who responded to treatment based on a less conservative definition of response later received 8 weeks of open-label methylphenidate at an individually determined best dose.

Adverse events such as decreased appetite and increased repetitive behavior and stereotypies occurred mainly with the highest dose, even though it was “not really that high” (0.5–0.6 mg/kg per dose), Dr. Scahill said. Few adverse events occurred in the 38% (25 of 66) of patients who responded to either the low dose (0.125–0.18 mg/kg per dose) or the medium dose (0.25–0.35 mg/kg per dose).

NEW YORK — The body of data for using newer pharmacotherapeutic agents to treat autistic symptoms is struggling to keep up with the use of such drugs in practice, Lawrence Scahill, Ph.D., said at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.

“An evidence-based discussion of autism is relatively brief, because we don't have a lot of evidence, unfortunately,” said Dr. Scahill, director of the research unit on pediatric psychopharmacology at the Yale Child Study Center, New Haven, Conn.

Some medications have proven to be useful in treating target symptoms of autism, such as hyperactivity, tantrums, aggression, self-injury, and anxiety, he said.

In a survey of medication patterns in patients with autism or pervasive developmental disorder (PDD) in North Carolina, the use of any medication to treat the conditions rose from 31% in 1992–1993 to 45% in 2001, Dr. Scahill noted (J. Child Adolesc. Psychopharmacol. 2005;15:116–26).

The use of several classes of drugs rose during that period, including antipsychotics (from 12% to 17%), antidepressants (from 6% to 21%), and stimulants (from 7% to 14%). For antipsychotics and antidepressants, these changes reflect switches to atypicals and SSRIs, said Dr. Scahill, who disclosed that he serves as a consultant for Janssen Pharmaceutica N.V., which manufactures risperidone (Risperdal), and Pfizer Inc., which manufactures fluoxetine.

SSRIs for Repetitive Behavior, Anxiety

SSRIs such as fluoxetine have been used in PDD to treat repetitive behavior, anxiety, and aggression, as well as to improve socialization, Dr. Scahill said.

Liquid fluoxetine proved to be more effective in treating repetitive behaviors than placebo in a randomized, double-blind, crossover study of 39 children and adolescents with autistic spectrum disorders. In the first phase of the trial, patients who received fluoxetine improved their scores on a clinician-rated instrument focused on repetitive behavior (the Children's Yale-Brown Obsessive Compulsive Scale-PDD) by 10%, compared with placebo patients who improved by 4%. The second phase of the study, in which the patients switched treatments, yielded similar results.

Adverse events occurred at a rate similar to that of placebo. The average dose of fluoxetine was 10 mg/day, beginning with 2.5 mg/day for the first week. “In terms of benefit, if you're aiming [SSRIs] at repetitive behavior, I don't say 'Don't do it,' but don't expect big effects,” he said.

Aggression, Tantrums, Self-Injury

Risperidone is the atypical antipsychotic that has been studied most extensively in PDD, with open and controlled trials involving a total of 223 patients.

The FDA previously declared risperidone as nonapprovable for the treatment of autism in children, but it is now being submitted for approval for the treatment of tantrums, aggression, and self-injury, Dr. Scahill said.

In an 8-week, randomized, double-blind trial, risperidone significantly reduced aggressive behavior, tantrums, and self-injurious behavior by 57% in 49 children, compared with 14% in 52 children on placebo, according to the parent-rated irritability subscale of the Aberrant Behavior Checklist. Clinician ratings yielded similar results. The patients averaged 1.8 mg/day (N. Engl. J. Med. 2002;347:314–21).

During a 4-month open-label extension of the study for 63 responders to risperidone, irritability scores did not worsen, and patients did not require more risperidone to maintain their response (Am. J. Psychiatry 2005;162:1361–9). These responders gained an average of 5.6 kg during a total of 6 months of treatment with risperidone (Am. J. Psychiatry 2004;161:1125–7).

In a 2-month, randomized, double-blind discontinuation of risperidone, patients who continued to receive risperidone had a significantly lower rate of relapse (2 of 16) than those who gradually replaced risperidone with placebo (10 of 16).

ADHD Symptoms

Even though hyperactivity is a common problem in children and adolescents with PDD, “the evidence to support the use of methylphenidate in this population is frightfully little,” Dr. Scahill said.

Until recently, methylphenidate had been studied in only two investigations of 10 children with PDD and ADHD. On the Conners Hyperactivity Index, teachers reported an 11% improvement at a dose of 10–20 mg twice daily (J. Autism Dev. Disord. 1995;25:283–94), 32% improvement at 0.3 mg/kg per dose, and 47% improvement at 0.6 mg/kg per dose (J. Am. Acad. Child Adolesc. Psychiatry 1999;38:805–12).

In a more rigorous study of 66 children with PDD and hyperactivity conducted by Dr. Scahill and his colleagues, methylphenidate improved hyperactivity significantly but less than it would in typically developing children with ADHD, according to teacher and parent ratings (Arch. Gen. Psychiatry 2005;62:1266–74). Children in the randomized, double-blind, crossover trial tolerated three dose levels of the drug in a 7-day test dose period and then received placebo for 1 week, followed by 3 weeks of the three methylphenidate doses in random order.

Thirty-four patients who responded to treatment based on a less conservative definition of response later received 8 weeks of open-label methylphenidate at an individually determined best dose.

Adverse events such as decreased appetite and increased repetitive behavior and stereotypies occurred mainly with the highest dose, even though it was “not really that high” (0.5–0.6 mg/kg per dose), Dr. Scahill said. Few adverse events occurred in the 38% (25 of 66) of patients who responded to either the low dose (0.125–0.18 mg/kg per dose) or the medium dose (0.25–0.35 mg/kg per dose).

NEW YORK — The body of data for using newer pharmacotherapeutic agents to treat autistic symptoms is struggling to keep up with the use of such drugs in practice, Lawrence Scahill, Ph.D., said at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.

“An evidence-based discussion of autism is relatively brief, because we don't have a lot of evidence, unfortunately,” said Dr. Scahill, director of the research unit on pediatric psychopharmacology at the Yale Child Study Center, New Haven, Conn.

Some medications have proven to be useful in treating target symptoms of autism, such as hyperactivity, tantrums, aggression, self-injury, and anxiety, he said.

In a survey of medication patterns in patients with autism or pervasive developmental disorder (PDD) in North Carolina, the use of any medication to treat the conditions rose from 31% in 1992–1993 to 45% in 2001, Dr. Scahill noted (J. Child Adolesc. Psychopharmacol. 2005;15:116–26).

The use of several classes of drugs rose during that period, including antipsychotics (from 12% to 17%), antidepressants (from 6% to 21%), and stimulants (from 7% to 14%). For antipsychotics and antidepressants, these changes reflect switches to atypicals and SSRIs, said Dr. Scahill, who disclosed that he serves as a consultant for Janssen Pharmaceutica N.V., which manufactures risperidone (Risperdal), and Pfizer Inc., which manufactures fluoxetine.

SSRIs for Repetitive Behavior, Anxiety

SSRIs such as fluoxetine have been used in PDD to treat repetitive behavior, anxiety, and aggression, as well as to improve socialization, Dr. Scahill said.

Liquid fluoxetine proved to be more effective in treating repetitive behaviors than placebo in a randomized, double-blind, crossover study of 39 children and adolescents with autistic spectrum disorders. In the first phase of the trial, patients who received fluoxetine improved their scores on a clinician-rated instrument focused on repetitive behavior (the Children's Yale-Brown Obsessive Compulsive Scale-PDD) by 10%, compared with placebo patients who improved by 4%. The second phase of the study, in which the patients switched treatments, yielded similar results.

Adverse events occurred at a rate similar to that of placebo. The average dose of fluoxetine was 10 mg/day, beginning with 2.5 mg/day for the first week. “In terms of benefit, if you're aiming [SSRIs] at repetitive behavior, I don't say 'Don't do it,' but don't expect big effects,” he said.

Aggression, Tantrums, Self-Injury

Risperidone is the atypical antipsychotic that has been studied most extensively in PDD, with open and controlled trials involving a total of 223 patients.

The FDA previously declared risperidone as nonapprovable for the treatment of autism in children, but it is now being submitted for approval for the treatment of tantrums, aggression, and self-injury, Dr. Scahill said.

In an 8-week, randomized, double-blind trial, risperidone significantly reduced aggressive behavior, tantrums, and self-injurious behavior by 57% in 49 children, compared with 14% in 52 children on placebo, according to the parent-rated irritability subscale of the Aberrant Behavior Checklist. Clinician ratings yielded similar results. The patients averaged 1.8 mg/day (N. Engl. J. Med. 2002;347:314–21).

During a 4-month open-label extension of the study for 63 responders to risperidone, irritability scores did not worsen, and patients did not require more risperidone to maintain their response (Am. J. Psychiatry 2005;162:1361–9). These responders gained an average of 5.6 kg during a total of 6 months of treatment with risperidone (Am. J. Psychiatry 2004;161:1125–7).

In a 2-month, randomized, double-blind discontinuation of risperidone, patients who continued to receive risperidone had a significantly lower rate of relapse (2 of 16) than those who gradually replaced risperidone with placebo (10 of 16).

ADHD Symptoms

Even though hyperactivity is a common problem in children and adolescents with PDD, “the evidence to support the use of methylphenidate in this population is frightfully little,” Dr. Scahill said.

Until recently, methylphenidate had been studied in only two investigations of 10 children with PDD and ADHD. On the Conners Hyperactivity Index, teachers reported an 11% improvement at a dose of 10–20 mg twice daily (J. Autism Dev. Disord. 1995;25:283–94), 32% improvement at 0.3 mg/kg per dose, and 47% improvement at 0.6 mg/kg per dose (J. Am. Acad. Child Adolesc. Psychiatry 1999;38:805–12).

In a more rigorous study of 66 children with PDD and hyperactivity conducted by Dr. Scahill and his colleagues, methylphenidate improved hyperactivity significantly but less than it would in typically developing children with ADHD, according to teacher and parent ratings (Arch. Gen. Psychiatry 2005;62:1266–74). Children in the randomized, double-blind, crossover trial tolerated three dose levels of the drug in a 7-day test dose period and then received placebo for 1 week, followed by 3 weeks of the three methylphenidate doses in random order.

Thirty-four patients who responded to treatment based on a less conservative definition of response later received 8 weeks of open-label methylphenidate at an individually determined best dose.

Adverse events such as decreased appetite and increased repetitive behavior and stereotypies occurred mainly with the highest dose, even though it was “not really that high” (0.5–0.6 mg/kg per dose), Dr. Scahill said. Few adverse events occurred in the 38% (25 of 66) of patients who responded to either the low dose (0.125–0.18 mg/kg per dose) or the medium dose (0.25–0.35 mg/kg per dose).

WASHINGTON — The severity of disease caused by Shiga toxin-producing bacteria may be tracked with a new scale under development that uses clinical markers of disease rather than direct measurement of toxin load, Dr. Martin M. Bitzan reported at a biodefense research meeting sponsored by the American Society for Microbiology.

“While the clinical diagnosis of hemolytic uremic syndrome appears straightforward, there are no defined criteria to describe and grade the severity of hemolytic uremic syndrome or of the preceding gastrointestinal disease,” Dr. Bitzan of the department of nephrology at Montreal Children's Hospital wrote in a poster presentation.

The inability to measure Shiga toxin in body fluids makes the development of proxy markers necessary, he and his colleague noted. Most of the infections in North America are due to Escherichia coli O157:H7.

The investigators developed a disease severity scale comprising four facets of Shiga toxin-producing infections: enteropathy (stool frequency, bloody diarrhea, abdominal pain); inflammation and vasculopathy (fever, peripheral leukocytosis, hypoalbuminemia); thrombotic microangiopathy (low hemoglobin and platelet levels); and nephropathy (hematuria, proteinuria, pyuria, hyponatremia, high serum creatinine).

They tested their scale on a database of 146 consecutive children aged 1–16 years with Shiga toxin-producing E. coli who had bloody (85%) or nonbloody (15%) diarrhea that resulted in partial (5%) or complete (13%) hemolytic uremic syndrome (HUS).

The scores of the children with HUS on all the scale's components except enteropathy became significantly worse 3–5 days after disease onset than children without the syndrome. The symptoms of those three components continued to be worse 11–14 days after disease onset, defined as the first day of diarrheal symptoms. Most children visited the ED for the first time 3 days after onset.

The scale is being validated in an international, prospective, observational study for disease follow-up.

WASHINGTON — The severity of disease caused by Shiga toxin-producing bacteria may be tracked with a new scale under development that uses clinical markers of disease rather than direct measurement of toxin load, Dr. Martin M. Bitzan reported at a biodefense research meeting sponsored by the American Society for Microbiology.

“While the clinical diagnosis of hemolytic uremic syndrome appears straightforward, there are no defined criteria to describe and grade the severity of hemolytic uremic syndrome or of the preceding gastrointestinal disease,” Dr. Bitzan of the department of nephrology at Montreal Children's Hospital wrote in a poster presentation.

The inability to measure Shiga toxin in body fluids makes the development of proxy markers necessary, he and his colleague noted. Most of the infections in North America are due to Escherichia coli O157:H7.

The investigators developed a disease severity scale comprising four facets of Shiga toxin-producing infections: enteropathy (stool frequency, bloody diarrhea, abdominal pain); inflammation and vasculopathy (fever, peripheral leukocytosis, hypoalbuminemia); thrombotic microangiopathy (low hemoglobin and platelet levels); and nephropathy (hematuria, proteinuria, pyuria, hyponatremia, high serum creatinine).

They tested their scale on a database of 146 consecutive children aged 1–16 years with Shiga toxin-producing E. coli who had bloody (85%) or nonbloody (15%) diarrhea that resulted in partial (5%) or complete (13%) hemolytic uremic syndrome (HUS).

The scores of the children with HUS on all the scale's components except enteropathy became significantly worse 3–5 days after disease onset than children without the syndrome. The symptoms of those three components continued to be worse 11–14 days after disease onset, defined as the first day of diarrheal symptoms. Most children visited the ED for the first time 3 days after onset.

The scale is being validated in an international, prospective, observational study for disease follow-up.

WASHINGTON — The severity of disease caused by Shiga toxin-producing bacteria may be tracked with a new scale under development that uses clinical markers of disease rather than direct measurement of toxin load, Dr. Martin M. Bitzan reported at a biodefense research meeting sponsored by the American Society for Microbiology.

“While the clinical diagnosis of hemolytic uremic syndrome appears straightforward, there are no defined criteria to describe and grade the severity of hemolytic uremic syndrome or of the preceding gastrointestinal disease,” Dr. Bitzan of the department of nephrology at Montreal Children's Hospital wrote in a poster presentation.

The inability to measure Shiga toxin in body fluids makes the development of proxy markers necessary, he and his colleague noted. Most of the infections in North America are due to Escherichia coli O157:H7.

The investigators developed a disease severity scale comprising four facets of Shiga toxin-producing infections: enteropathy (stool frequency, bloody diarrhea, abdominal pain); inflammation and vasculopathy (fever, peripheral leukocytosis, hypoalbuminemia); thrombotic microangiopathy (low hemoglobin and platelet levels); and nephropathy (hematuria, proteinuria, pyuria, hyponatremia, high serum creatinine).

They tested their scale on a database of 146 consecutive children aged 1–16 years with Shiga toxin-producing E. coli who had bloody (85%) or nonbloody (15%) diarrhea that resulted in partial (5%) or complete (13%) hemolytic uremic syndrome (HUS).

The scores of the children with HUS on all the scale's components except enteropathy became significantly worse 3–5 days after disease onset than children without the syndrome. The symptoms of those three components continued to be worse 11–14 days after disease onset, defined as the first day of diarrheal symptoms. Most children visited the ED for the first time 3 days after onset.

The scale is being validated in an international, prospective, observational study for disease follow-up.

WASHINGTON — Methods are now available to produce influenza virus vaccines in a greater number of doses and with more up-to-date coverage of relevant strains than what is currently available, Peter Palese, Ph.D., said at a biodefense research meeting sponsored by the American Society for Microbiology.

In most instances, these methods can be applied to both killed (inactivated) and live (attenuated) vaccines, said Dr. Palese, chair of microbiology at Mount Sinai Medical Center, New York.

Viruses that are used in killed vaccines are grown in embryonated eggs, purified, inactivated with formaldehyde, and usually then treated with a detergent to make the vaccine less pyrogenic.

The recently approved live vaccines are grown in tissue culture at a lower temperature (25° C) and in embryonated eggs, which makes the virus temperature-sensitive and attenuated; this limits the virus to a few replication cycles in the upper respiratory tract, he said.

New adjuvants should help to reduce the amount of antigenic viral material in each vaccine dose that is necessary to induce protective immunity, Dr. Palese said.

If adjuvants were used, the antigenic mass in each vaccine dose could be reduced to 10%–20% of its current amount. Alum is the only adjuvant approved by the Food and Drug Administration to be given in combination with some vaccines.

“This is an area where we really have to improve,” he said.

Each February, the FDA decides which strains should be included in vaccines for the next influenza season. Only the viruses that are circulating until the end of January can be considered in the decision.

The FDA would make better decisions about which influenza isolates should be included in the vaccine if the decision could be delayed until May or June, Dr. Palese said.

Vaccines used in the 2005–2006 season were trivalent with surface antigens from an influenza A H3N2 isolate from 2004, an older influenza A H1N1 isolate from 1999, and an influenza B isolate from 2002. One or two of the three components changes each flu season, Dr. Palese said.

A new technique may allow researchers to adjust the viral antigens in vaccines and produce vaccines more quickly. It would work by inserting a combination of DNA copies of specific genes from a laboratory viral strain and genes for the hemagglutinin and neuraminidase antigens on currently circulating viruses into cells in a tissue culture.

The resulting recombinant seed viruses could then be generated in a 1− to 2-week period for distribution to manufacturers for annual vaccine production. This process allows more time to select the appropriate antigenic seed strains, he said.

Vaccine developers also may be able to use this process to engineer the influenza virus genome to express an altered version of nonstructural protein 1 (NS1). NS1 normally inhibits the interferon response of a host cell; viruses that lack NS1 cannot block interferon and, as a result, cannot replicate.

WASHINGTON — Methods are now available to produce influenza virus vaccines in a greater number of doses and with more up-to-date coverage of relevant strains than what is currently available, Peter Palese, Ph.D., said at a biodefense research meeting sponsored by the American Society for Microbiology.

In most instances, these methods can be applied to both killed (inactivated) and live (attenuated) vaccines, said Dr. Palese, chair of microbiology at Mount Sinai Medical Center, New York.

Viruses that are used in killed vaccines are grown in embryonated eggs, purified, inactivated with formaldehyde, and usually then treated with a detergent to make the vaccine less pyrogenic.

The recently approved live vaccines are grown in tissue culture at a lower temperature (25° C) and in embryonated eggs, which makes the virus temperature-sensitive and attenuated; this limits the virus to a few replication cycles in the upper respiratory tract, he said.

New adjuvants should help to reduce the amount of antigenic viral material in each vaccine dose that is necessary to induce protective immunity, Dr. Palese said.

If adjuvants were used, the antigenic mass in each vaccine dose could be reduced to 10%–20% of its current amount. Alum is the only adjuvant approved by the Food and Drug Administration to be given in combination with some vaccines.

“This is an area where we really have to improve,” he said.

Each February, the FDA decides which strains should be included in vaccines for the next influenza season. Only the viruses that are circulating until the end of January can be considered in the decision.

The FDA would make better decisions about which influenza isolates should be included in the vaccine if the decision could be delayed until May or June, Dr. Palese said.

Vaccines used in the 2005–2006 season were trivalent with surface antigens from an influenza A H3N2 isolate from 2004, an older influenza A H1N1 isolate from 1999, and an influenza B isolate from 2002. One or two of the three components changes each flu season, Dr. Palese said.

A new technique may allow researchers to adjust the viral antigens in vaccines and produce vaccines more quickly. It would work by inserting a combination of DNA copies of specific genes from a laboratory viral strain and genes for the hemagglutinin and neuraminidase antigens on currently circulating viruses into cells in a tissue culture.

The resulting recombinant seed viruses could then be generated in a 1− to 2-week period for distribution to manufacturers for annual vaccine production. This process allows more time to select the appropriate antigenic seed strains, he said.

Vaccine developers also may be able to use this process to engineer the influenza virus genome to express an altered version of nonstructural protein 1 (NS1). NS1 normally inhibits the interferon response of a host cell; viruses that lack NS1 cannot block interferon and, as a result, cannot replicate.

WASHINGTON — Methods are now available to produce influenza virus vaccines in a greater number of doses and with more up-to-date coverage of relevant strains than what is currently available, Peter Palese, Ph.D., said at a biodefense research meeting sponsored by the American Society for Microbiology.

In most instances, these methods can be applied to both killed (inactivated) and live (attenuated) vaccines, said Dr. Palese, chair of microbiology at Mount Sinai Medical Center, New York.

Viruses that are used in killed vaccines are grown in embryonated eggs, purified, inactivated with formaldehyde, and usually then treated with a detergent to make the vaccine less pyrogenic.

The recently approved live vaccines are grown in tissue culture at a lower temperature (25° C) and in embryonated eggs, which makes the virus temperature-sensitive and attenuated; this limits the virus to a few replication cycles in the upper respiratory tract, he said.

New adjuvants should help to reduce the amount of antigenic viral material in each vaccine dose that is necessary to induce protective immunity, Dr. Palese said.

If adjuvants were used, the antigenic mass in each vaccine dose could be reduced to 10%–20% of its current amount. Alum is the only adjuvant approved by the Food and Drug Administration to be given in combination with some vaccines.

“This is an area where we really have to improve,” he said.

Each February, the FDA decides which strains should be included in vaccines for the next influenza season. Only the viruses that are circulating until the end of January can be considered in the decision.

The FDA would make better decisions about which influenza isolates should be included in the vaccine if the decision could be delayed until May or June, Dr. Palese said.

Vaccines used in the 2005–2006 season were trivalent with surface antigens from an influenza A H3N2 isolate from 2004, an older influenza A H1N1 isolate from 1999, and an influenza B isolate from 2002. One or two of the three components changes each flu season, Dr. Palese said.

A new technique may allow researchers to adjust the viral antigens in vaccines and produce vaccines more quickly. It would work by inserting a combination of DNA copies of specific genes from a laboratory viral strain and genes for the hemagglutinin and neuraminidase antigens on currently circulating viruses into cells in a tissue culture.

The resulting recombinant seed viruses could then be generated in a 1− to 2-week period for distribution to manufacturers for annual vaccine production. This process allows more time to select the appropriate antigenic seed strains, he said.

Vaccine developers also may be able to use this process to engineer the influenza virus genome to express an altered version of nonstructural protein 1 (NS1). NS1 normally inhibits the interferon response of a host cell; viruses that lack NS1 cannot block interferon and, as a result, cannot replicate.

WASHINGTON — Methods are now available to produce influenza virus vaccines in a greater number of doses and with more up-to-date coverage of relevant strains than what is currently available, Peter Palese, Ph.D., said at a biodefense research meeting sponsored by the American Society for Microbiology.

In most instances, these methods can be applied to both killed (inactivated) and live (attenuated) vaccines, said Dr. Palese, chair of microbiology at Mount Sinai Medical Center, New York.

Viruses in killed vaccines are grown in embryonated eggs, purified, inactivated with formaldehyde, and usually then treated with a detergent to make the vaccine less pyrogenic. The recently approved live vaccines are grown in tissue culture at a lower temperature (25° C) and in embryonated eggs. This makes the virus temperature-sensitive and attenuated, limiting the virus to a few replication cycles in the upper respiratory tract.

New adjuvants should help reduce the amount of antigenic viral material in each vaccine dose that is needed to induce protective immunity, he said. With adjuvants, the antigenic mass in each dose could be reduced to anywhere from a fifth to a tenth of its current amount. Alum is the only adjuvant approved by the Food and Drug Administration for use in combination with some vaccines.

“This is an area where we really have to improve,” he said.

Each February, the FDA decides which strains should be included in vaccines for the next influenza season. Only the viruses that are circulating until the end of January can be considered in the decision. The FDA would make better decisions about which influenza isolates should be included in the vaccine if the decision could be delayed until May or June, Dr. Palese said.

Vaccines for the 2005–2006 season were trivalent with surface antigens from an influenza A H3N2 isolate from 2004, an older influenza A H1N1 isolate from 1999, and an influenza B isolate from 2002. One or two of the three components changes each flu season, Dr. Palese noted.

A new technique may let researchers adjust the viral antigens in vaccines and produce vaccines more quickly. It would work by inserting a combination of DNA copies of specific genes from a laboratory viral strain and genes for the hemagglutinin and neuraminidase antigens on currently circulating viruses into cells in a tissue culture. The resulting recombinant seed viruses could then be generated within 1 to 2 weeks for distribution to manufacturers for annual vaccine production.

This process allows more time to select the appropriate antigenic seed strains, he said.

Vaccine developers also may be able to use this process to engineer the influenza virus genome to express an altered version of nonstructural protein 1 (NS1). NS1 normally inhibits the interferon response of a host cell; viruses that lack NS1 cannot block interferon and, as a result, cannot replicate. Viruses with a truncated version of NS1 are still able to replicate, although not as easily as those with normal NS1, because the truncated protein induces an interferon response from the host cell. Viruses with truncated NS1 are attenuated and have been shown to immunize mice against challenges with high doses of active virus.

The viruses with truncated NS1 are highly immunogenic because interferon acts as an adjuvant by enhancing the production of immunoglobulins and contributing to the activation of dendritic cells required for antigen presentation. The robust immune response to these viruses could make it possible to scale down the amount of infectious agents in each dose by several orders of magnitude; many more doses could be manufactured in this way, Dr. Palese said.

WASHINGTON — Methods are now available to produce influenza virus vaccines in a greater number of doses and with more up-to-date coverage of relevant strains than what is currently available, Peter Palese, Ph.D., said at a biodefense research meeting sponsored by the American Society for Microbiology.

In most instances, these methods can be applied to both killed (inactivated) and live (attenuated) vaccines, said Dr. Palese, chair of microbiology at Mount Sinai Medical Center, New York.

Viruses in killed vaccines are grown in embryonated eggs, purified, inactivated with formaldehyde, and usually then treated with a detergent to make the vaccine less pyrogenic. The recently approved live vaccines are grown in tissue culture at a lower temperature (25° C) and in embryonated eggs. This makes the virus temperature-sensitive and attenuated, limiting the virus to a few replication cycles in the upper respiratory tract.

New adjuvants should help reduce the amount of antigenic viral material in each vaccine dose that is needed to induce protective immunity, he said. With adjuvants, the antigenic mass in each dose could be reduced to anywhere from a fifth to a tenth of its current amount. Alum is the only adjuvant approved by the Food and Drug Administration for use in combination with some vaccines.

“This is an area where we really have to improve,” he said.

Each February, the FDA decides which strains should be included in vaccines for the next influenza season. Only the viruses that are circulating until the end of January can be considered in the decision. The FDA would make better decisions about which influenza isolates should be included in the vaccine if the decision could be delayed until May or June, Dr. Palese said.

Vaccines for the 2005–2006 season were trivalent with surface antigens from an influenza A H3N2 isolate from 2004, an older influenza A H1N1 isolate from 1999, and an influenza B isolate from 2002. One or two of the three components changes each flu season, Dr. Palese noted.

A new technique may let researchers adjust the viral antigens in vaccines and produce vaccines more quickly. It would work by inserting a combination of DNA copies of specific genes from a laboratory viral strain and genes for the hemagglutinin and neuraminidase antigens on currently circulating viruses into cells in a tissue culture. The resulting recombinant seed viruses could then be generated within 1 to 2 weeks for distribution to manufacturers for annual vaccine production.

This process allows more time to select the appropriate antigenic seed strains, he said.

Vaccine developers also may be able to use this process to engineer the influenza virus genome to express an altered version of nonstructural protein 1 (NS1). NS1 normally inhibits the interferon response of a host cell; viruses that lack NS1 cannot block interferon and, as a result, cannot replicate. Viruses with a truncated version of NS1 are still able to replicate, although not as easily as those with normal NS1, because the truncated protein induces an interferon response from the host cell. Viruses with truncated NS1 are attenuated and have been shown to immunize mice against challenges with high doses of active virus.

The viruses with truncated NS1 are highly immunogenic because interferon acts as an adjuvant by enhancing the production of immunoglobulins and contributing to the activation of dendritic cells required for antigen presentation. The robust immune response to these viruses could make it possible to scale down the amount of infectious agents in each dose by several orders of magnitude; many more doses could be manufactured in this way, Dr. Palese said.

WASHINGTON — Methods are now available to produce influenza virus vaccines in a greater number of doses and with more up-to-date coverage of relevant strains than what is currently available, Peter Palese, Ph.D., said at a biodefense research meeting sponsored by the American Society for Microbiology.

In most instances, these methods can be applied to both killed (inactivated) and live (attenuated) vaccines, said Dr. Palese, chair of microbiology at Mount Sinai Medical Center, New York.

Viruses in killed vaccines are grown in embryonated eggs, purified, inactivated with formaldehyde, and usually then treated with a detergent to make the vaccine less pyrogenic. The recently approved live vaccines are grown in tissue culture at a lower temperature (25° C) and in embryonated eggs. This makes the virus temperature-sensitive and attenuated, limiting the virus to a few replication cycles in the upper respiratory tract.

New adjuvants should help reduce the amount of antigenic viral material in each vaccine dose that is needed to induce protective immunity, he said. With adjuvants, the antigenic mass in each dose could be reduced to anywhere from a fifth to a tenth of its current amount. Alum is the only adjuvant approved by the Food and Drug Administration for use in combination with some vaccines.

“This is an area where we really have to improve,” he said.

Each February, the FDA decides which strains should be included in vaccines for the next influenza season. Only the viruses that are circulating until the end of January can be considered in the decision. The FDA would make better decisions about which influenza isolates should be included in the vaccine if the decision could be delayed until May or June, Dr. Palese said.

Vaccines for the 2005–2006 season were trivalent with surface antigens from an influenza A H3N2 isolate from 2004, an older influenza A H1N1 isolate from 1999, and an influenza B isolate from 2002. One or two of the three components changes each flu season, Dr. Palese noted.

A new technique may let researchers adjust the viral antigens in vaccines and produce vaccines more quickly. It would work by inserting a combination of DNA copies of specific genes from a laboratory viral strain and genes for the hemagglutinin and neuraminidase antigens on currently circulating viruses into cells in a tissue culture. The resulting recombinant seed viruses could then be generated within 1 to 2 weeks for distribution to manufacturers for annual vaccine production.

This process allows more time to select the appropriate antigenic seed strains, he said.

Vaccine developers also may be able to use this process to engineer the influenza virus genome to express an altered version of nonstructural protein 1 (NS1). NS1 normally inhibits the interferon response of a host cell; viruses that lack NS1 cannot block interferon and, as a result, cannot replicate. Viruses with a truncated version of NS1 are still able to replicate, although not as easily as those with normal NS1, because the truncated protein induces an interferon response from the host cell. Viruses with truncated NS1 are attenuated and have been shown to immunize mice against challenges with high doses of active virus.

The viruses with truncated NS1 are highly immunogenic because interferon acts as an adjuvant by enhancing the production of immunoglobulins and contributing to the activation of dendritic cells required for antigen presentation. The robust immune response to these viruses could make it possible to scale down the amount of infectious agents in each dose by several orders of magnitude; many more doses could be manufactured in this way, Dr. Palese said.

NEW YORK — Significant growth slowdown during treatment with stimulants may occur in a small subset of children who require closer monitoring and referral, Dr. Harold E. Carlson said at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.

“It's pretty well established that children who receive stimulants, typically for [attention-deficit hyperactivity disorder], can have some slowing of their growth,” said Dr. Carlson, head of endocrinology at the State University of New York at Stony Brook.

Height velocity, or yearly growth, typically slows for the first few years of stimulant therapy and then resumes at a nearly normal rate. Pubertal development is normal. Final adult height is usually normal with long-term use of stimulants. However, a small subset of patients, perhaps 10%, have a more significant slowdown of growth, Dr. Carlson said.

“I don't think anybody has a good handle on how many [children experience this significant slowdown], and we certainly don't have a good idea as to how to identify them ahead of time,” he said.

Because the secretion of growth hormone in these children is normal, researchers have speculated that the slowdown may be related to a decrease in food intake while on stimulants, he said.

The slowdown is greater in prepubertal children, boys, children who are taller or overweight at baseline, and children who use sustained-release formulations.

Little data exist on the final adult height of children who have taken stimulants, Dr. Carlson said.

In one study, 97 boys aged 4–12 years who were treated with methylphenidate for an average of 36 months grew to a final adult height at 21–23 years of age that was similar to the final adult height of other males in their family and community, and of unmedicated controls. These data are “reassuring,” Dr. Carlson said, but “we want to emphasize that there may well be a subset of children who do have more significant slowing of growth.”

NEW YORK — Significant growth slowdown during treatment with stimulants may occur in a small subset of children who require closer monitoring and referral, Dr. Harold E. Carlson said at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.

“It's pretty well established that children who receive stimulants, typically for [attention-deficit hyperactivity disorder], can have some slowing of their growth,” said Dr. Carlson, head of endocrinology at the State University of New York at Stony Brook.

Height velocity, or yearly growth, typically slows for the first few years of stimulant therapy and then resumes at a nearly normal rate. Pubertal development is normal. Final adult height is usually normal with long-term use of stimulants. However, a small subset of patients, perhaps 10%, have a more significant slowdown of growth, Dr. Carlson said.

“I don't think anybody has a good handle on how many [children experience this significant slowdown], and we certainly don't have a good idea as to how to identify them ahead of time,” he said.

Because the secretion of growth hormone in these children is normal, researchers have speculated that the slowdown may be related to a decrease in food intake while on stimulants, he said.

The slowdown is greater in prepubertal children, boys, children who are taller or overweight at baseline, and children who use sustained-release formulations.

Little data exist on the final adult height of children who have taken stimulants, Dr. Carlson said.

In one study, 97 boys aged 4–12 years who were treated with methylphenidate for an average of 36 months grew to a final adult height at 21–23 years of age that was similar to the final adult height of other males in their family and community, and of unmedicated controls. These data are “reassuring,” Dr. Carlson said, but “we want to emphasize that there may well be a subset of children who do have more significant slowing of growth.”

NEW YORK — Significant growth slowdown during treatment with stimulants may occur in a small subset of children who require closer monitoring and referral, Dr. Harold E. Carlson said at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.

“It's pretty well established that children who receive stimulants, typically for [attention-deficit hyperactivity disorder], can have some slowing of their growth,” said Dr. Carlson, head of endocrinology at the State University of New York at Stony Brook.

Height velocity, or yearly growth, typically slows for the first few years of stimulant therapy and then resumes at a nearly normal rate. Pubertal development is normal. Final adult height is usually normal with long-term use of stimulants. However, a small subset of patients, perhaps 10%, have a more significant slowdown of growth, Dr. Carlson said.

“I don't think anybody has a good handle on how many [children experience this significant slowdown], and we certainly don't have a good idea as to how to identify them ahead of time,” he said.

Because the secretion of growth hormone in these children is normal, researchers have speculated that the slowdown may be related to a decrease in food intake while on stimulants, he said.

The slowdown is greater in prepubertal children, boys, children who are taller or overweight at baseline, and children who use sustained-release formulations.

Little data exist on the final adult height of children who have taken stimulants, Dr. Carlson said.

In one study, 97 boys aged 4–12 years who were treated with methylphenidate for an average of 36 months grew to a final adult height at 21–23 years of age that was similar to the final adult height of other males in their family and community, and of unmedicated controls. These data are “reassuring,” Dr. Carlson said, but “we want to emphasize that there may well be a subset of children who do have more significant slowing of growth.”