Christine Kilgore

A program that sends nurses to visit economically disadvantaged, single mothers during pregnancy and for the child's first 2 years can have long-term benefits, recent data show.

The analysis, which was recently commissioned by the Washington state legislature, shows the largest cost savings of any home visit, child welfare, or early intervention program.

The home visitation program has been developed over 25 years and operates in 21 states and focuses on improving birth outcomes, parenting skills, and children's health and development. It also promotes economic self-sufficiency for families.

Each mother in the Nurse-Family Partnership, develops a long-term relationship with one nurse who follows detailed guidelines and is trained in prenatal care and early child development.

The latest data, published in two articles in the journal Pediatrics, are from controlled, randomized trials conducted in two settings: among low-income African American mothers in Memphis, and among an ethnically and racially diverse group of low-income Denver women.

The women and children in Memphis were interviewed and evaluated 4 years after the program ended, near the child's sixth birthday. Those in Denver were evaluated 2 years after the program ended.

“The effects of the program … increase the likelihood that nurse-visited children will adjust more effectively as they proceed through elementary school,” reported David L. Olds, Ph.D., of the department of pediatrics at the University of Colorado Health Sciences Center in Denver, and his associates (Pediatrics 2004;114:1550–9).

Of the 743 women in Memphis who were randomized to the nurse home visitation program or one of three other intervention groups, those enrolled in the nurse visitation program had fewer subsequent pregnancies and births (1 vs. 1.3 births), and longer intervals between births of their first and second children (34 vs. 30 months).

They also had longer relationships with their partners, used welfare and food stamps for fewer months, and were more likely to enroll their children in some form of preschool or licensed day care.

The children of these nurse-visited women had higher scores on tests of intellectual functioning and receptive language, and fewer behavioral problems in the borderline or clinical range (2% vs. 5%, based on the Achenbach Child Behavior Checklist).

Among children born to women with low psychological resources (limited intellectual functioning, mental health, and sense of control), those whose mothers met with the nurses had higher arithmetic achievement test scores and expressed less dysregulated aggression and incoherence when asked to respond to and finish story beginnings, the investigators said.

The program “is so effective [because] they've tested [and shown] the importance of using nurses instead of social workers,” said Steve Aos, associate director of the Washington State Institute for Public Policy, a nonpartisan organization that produced the analysis that is now gaining focus in Washington state.

“And especially since the program has gone national, Dr. Olds makes sure the program is done by the book. … [He appears to have] hit on a better theoretical model for intervention,” Mr. Aos said.

Dr. Olds, who developed and has refined the program over the years, said he hopes to examine more the extent to which the program produces comparable effects across different populations. Some effects—such as reductions in prenatal tobacco use and reductions in the rates and intervals of subsequent pregnancies-—seem to be fairly consistent. Other effects vary among populations.

The first trial of the program, which began about 20 years ago, involved low-income white families in rural New York. Researchers found less alcohol use and better behavior among teenage children of nurse-visited mothers has been published, and the families are still being followed.

The evaluation done by Mr. Aos' organization at the request of the Washington state legislature showed that the Nurse-Family Partnership costs about $9,000 per family and had a record net benefit of more than $17,000 per youth, in terms of welfare, criminal justice system, medical, and other cost savings.

Most of the 160 Nurse-Family Partnership programs across the country are administered through county health programs. In the long term, however, “things will have to change—there just aren't enough funding streams,” said Matt Buhr-Vogel, manager of site development for the new Nurse-Family Partnership national office in Denver.

A program that sends nurses to visit economically disadvantaged, single mothers during pregnancy and for the child's first 2 years can have long-term benefits, recent data show.

The analysis, which was recently commissioned by the Washington state legislature, shows the largest cost savings of any home visit, child welfare, or early intervention program.

The home visitation program has been developed over 25 years and operates in 21 states and focuses on improving birth outcomes, parenting skills, and children's health and development. It also promotes economic self-sufficiency for families.

Each mother in the Nurse-Family Partnership, develops a long-term relationship with one nurse who follows detailed guidelines and is trained in prenatal care and early child development.

The latest data, published in two articles in the journal Pediatrics, are from controlled, randomized trials conducted in two settings: among low-income African American mothers in Memphis, and among an ethnically and racially diverse group of low-income Denver women.

The women and children in Memphis were interviewed and evaluated 4 years after the program ended, near the child's sixth birthday. Those in Denver were evaluated 2 years after the program ended.

“The effects of the program … increase the likelihood that nurse-visited children will adjust more effectively as they proceed through elementary school,” reported David L. Olds, Ph.D., of the department of pediatrics at the University of Colorado Health Sciences Center in Denver, and his associates (Pediatrics 2004;114:1550–9).

Of the 743 women in Memphis who were randomized to the nurse home visitation program or one of three other intervention groups, those enrolled in the nurse visitation program had fewer subsequent pregnancies and births (1 vs. 1.3 births), and longer intervals between births of their first and second children (34 vs. 30 months).

They also had longer relationships with their partners, used welfare and food stamps for fewer months, and were more likely to enroll their children in some form of preschool or licensed day care.

The children of these nurse-visited women had higher scores on tests of intellectual functioning and receptive language, and fewer behavioral problems in the borderline or clinical range (2% vs. 5%, based on the Achenbach Child Behavior Checklist).

Among children born to women with low psychological resources (limited intellectual functioning, mental health, and sense of control), those whose mothers met with the nurses had higher arithmetic achievement test scores and expressed less dysregulated aggression and incoherence when asked to respond to and finish story beginnings, the investigators said.

The program “is so effective [because] they've tested [and shown] the importance of using nurses instead of social workers,” said Steve Aos, associate director of the Washington State Institute for Public Policy, a nonpartisan organization that produced the analysis that is now gaining focus in Washington state.

“And especially since the program has gone national, Dr. Olds makes sure the program is done by the book. … [He appears to have] hit on a better theoretical model for intervention,” Mr. Aos said.

Dr. Olds, who developed and has refined the program over the years, said he hopes to examine more the extent to which the program produces comparable effects across different populations. Some effects—such as reductions in prenatal tobacco use and reductions in the rates and intervals of subsequent pregnancies-—seem to be fairly consistent. Other effects vary among populations.

The first trial of the program, which began about 20 years ago, involved low-income white families in rural New York. Researchers found less alcohol use and better behavior among teenage children of nurse-visited mothers has been published, and the families are still being followed.

The evaluation done by Mr. Aos' organization at the request of the Washington state legislature showed that the Nurse-Family Partnership costs about $9,000 per family and had a record net benefit of more than $17,000 per youth, in terms of welfare, criminal justice system, medical, and other cost savings.

Most of the 160 Nurse-Family Partnership programs across the country are administered through county health programs. In the long term, however, “things will have to change—there just aren't enough funding streams,” said Matt Buhr-Vogel, manager of site development for the new Nurse-Family Partnership national office in Denver.

A program that sends nurses to visit economically disadvantaged, single mothers during pregnancy and for the child's first 2 years can have long-term benefits, recent data show.

The analysis, which was recently commissioned by the Washington state legislature, shows the largest cost savings of any home visit, child welfare, or early intervention program.

The home visitation program has been developed over 25 years and operates in 21 states and focuses on improving birth outcomes, parenting skills, and children's health and development. It also promotes economic self-sufficiency for families.

Each mother in the Nurse-Family Partnership, develops a long-term relationship with one nurse who follows detailed guidelines and is trained in prenatal care and early child development.

The latest data, published in two articles in the journal Pediatrics, are from controlled, randomized trials conducted in two settings: among low-income African American mothers in Memphis, and among an ethnically and racially diverse group of low-income Denver women.

The women and children in Memphis were interviewed and evaluated 4 years after the program ended, near the child's sixth birthday. Those in Denver were evaluated 2 years after the program ended.

“The effects of the program … increase the likelihood that nurse-visited children will adjust more effectively as they proceed through elementary school,” reported David L. Olds, Ph.D., of the department of pediatrics at the University of Colorado Health Sciences Center in Denver, and his associates (Pediatrics 2004;114:1550–9).

Of the 743 women in Memphis who were randomized to the nurse home visitation program or one of three other intervention groups, those enrolled in the nurse visitation program had fewer subsequent pregnancies and births (1 vs. 1.3 births), and longer intervals between births of their first and second children (34 vs. 30 months).

They also had longer relationships with their partners, used welfare and food stamps for fewer months, and were more likely to enroll their children in some form of preschool or licensed day care.

The children of these nurse-visited women had higher scores on tests of intellectual functioning and receptive language, and fewer behavioral problems in the borderline or clinical range (2% vs. 5%, based on the Achenbach Child Behavior Checklist).

Among children born to women with low psychological resources (limited intellectual functioning, mental health, and sense of control), those whose mothers met with the nurses had higher arithmetic achievement test scores and expressed less dysregulated aggression and incoherence when asked to respond to and finish story beginnings, the investigators said.

The program “is so effective [because] they've tested [and shown] the importance of using nurses instead of social workers,” said Steve Aos, associate director of the Washington State Institute for Public Policy, a nonpartisan organization that produced the analysis that is now gaining focus in Washington state.

“And especially since the program has gone national, Dr. Olds makes sure the program is done by the book. … [He appears to have] hit on a better theoretical model for intervention,” Mr. Aos said.

Dr. Olds, who developed and has refined the program over the years, said he hopes to examine more the extent to which the program produces comparable effects across different populations. Some effects—such as reductions in prenatal tobacco use and reductions in the rates and intervals of subsequent pregnancies-—seem to be fairly consistent. Other effects vary among populations.

The first trial of the program, which began about 20 years ago, involved low-income white families in rural New York. Researchers found less alcohol use and better behavior among teenage children of nurse-visited mothers has been published, and the families are still being followed.

The evaluation done by Mr. Aos' organization at the request of the Washington state legislature showed that the Nurse-Family Partnership costs about $9,000 per family and had a record net benefit of more than $17,000 per youth, in terms of welfare, criminal justice system, medical, and other cost savings.

Most of the 160 Nurse-Family Partnership programs across the country are administered through county health programs. In the long term, however, “things will have to change—there just aren't enough funding streams,” said Matt Buhr-Vogel, manager of site development for the new Nurse-Family Partnership national office in Denver.

Over the next several years, victims of car accidents, crimes, or other traumas treated at Boston's Massachusetts General Hospital will be offered a common heart drug—the β-adrenergic blocker propranolol—to potentially help lessen the intensity and impact of traumatic memories.

Participants in this study will be part of a wave of new drug trials aimed at intervening early to alter memory processes and prevent posttraumatic stress disorder (PTSD). Other studies are planned using later intervention to treat PTSD by affecting memory “reconsolidation,” the process by which memories that have been reactivated are stored again.

The study at Massachusetts General builds on a pilot study, published in 2002, that suggested that posttrauma administration of propranolol in the emergency room may have a “preventive effect” on subsequent PTSD. (See box.)

Roger Pitman, M.D., who led the pilot study and has a $2.5 million grant from the National Institutes of Mental Health to conduct the larger double-blind randomized study, hopes to recruit at least 100 patients who have experienced a traumatic event and present with tachycardia of at least 80 beats/min. According to Dr. Pittman, most studies addressing the issue of tachycardia as a predictor of PTSD “have been positive.”

Propranolol is commonly used to treat high blood pressure and for other cardiovascular purposes. It is also prescribed, albeit less frequently, as an antianxiety therapy adjunct for people with public speaking anxieties, fear of flying, and other phobias. It is the only β-blocker that can cross the blood-brain barrier, Dr. Pitman said.

Patients in his study will be randomized to receive, within 6 hours of the event, a 10-day course of placebo or propranolol followed by a 9-day taper period, said Dr. Pittman, professor of psychiatry at Harvard Medical School, Boston.

A major question faced by investigators concerns the timing of the memory consolidation processes. “We don't know what our window of opportunity is,” Dr. Pitman said. “In the most pessimistic estimate, it takes 30 minutes. And it takes at least 30 minutes for propranolol to be absorbed. Some data suggest, though, that the process may take 8 hours.”

Some physicians believe that it may be more feasible to intervene later and to work on memories that already have formed. The idea here is to reactivate or retrieve the memory and, while it is briefly vulnerable, attempt to weaken it before it is restored.

At the October meeting of the Society of Neuroscience, investigators from the Center for Neural Science at New York University presented preliminary findings that suggested propranolol at least partly disrupts the “reconsolidation” of fear memories, via the amygdala, significantly weakening the memories.

NYU physicians have begun working with others at the multi-institutional Center for the Neuroscience of Fear and Anxiety on testing whether propranolol helps PTSD patients who take it after recalling traumatic experiences.

Dr. Pitman also is planning a study with Karim Nader, Ph.D., a neuroscientist at McGill University in Montreal, in which they will reactivate traumatic memories of PTSD patients and measure the ability of propranolol to reduce the subsequent strength of the memories.

Other physicians have their eyes on the use of selective serotonin reuptake inhibitors (SSRIs) for PTSD prevention.

At Massachusetts General, Mark Pollack, M.D., is testing Lexapro (escitalopram) “at the next potential point of intervention”—in patients who, within a few weeks after trauma, are experiencing acute stress symptoms but do not meet the full criteria for PTSD.

The hope is that the drugs will help interrupt the cycle of increased arousal and anxiety that may presage full-blown PTSD, said Dr. Pollack, director of the hospital's Anxiety and Traumatic Stress Disorders Program. SSRIs are often used (with moderate success) to treat syndromal PTSD.

Physicians at the Center for the Study of Traumatic Stress at the Uniformed Health Services University of the Health Sciences in Bethesda, Md., have started a similar study, administering an SSRI to car accident victims days to several weeks after the event. Robert Ursano, M.D., who chairs the department of psychiatry at the university, is optimistic enough to say that “PTSD may be the first psychiatric illness that we–ll be able to prevent.”

Investigators are also encouraged by pharmacologic studies aimed at enhancing the process of fear extinction and making it a better adjunct to psychotherapy. One drug of interest is d-cycloserine, which enhances the activity of a protein in the amygdala that is important for fear extinction.

A recent study showed that patients with acrophobia who had exposure therapy combined with d-cycloserine had significantly larger reductions in their symptoms than patients who received placebo (Arch. Gen. Psychiatry 2004;61:1136–44).

Cycloserine could show similar effects for PTSD, said Michael Davis, Ph.D., professor of psychiatry and behavioral sciences at Emory University, Atlanta. “I–m not sure how good propranolol will be in the long run,” he said. “If you're trying to get rid of really traumatic fear memories, you need something to block not only the active recollection [of the event], but also the associated fear.

Small Studies of Propranolol Set Scene

Dr. Pitman's initial study of propranolol is one of two small pilot studies that looked at use of the drug shortly after a traumatic event.

Forty-one patients were randomized in the emergency department at Massachusetts General Hospital to begin—within 6 hours of a traumatic event—a 10-day course of propranolol (40 mg four times daily) or placebo. Eighteen of the 41 received propranolol.

Patients in the double-blind study were instructed to return 1 and 3 months later for assessment with the Clinician-Administered PTSD Scale (CAPS). At the 3-month follow-up, investigators also measured patients' physiologic responses during script-driven imagery of the traumatic event.

At 1 month, the PTSD rate was 30% in the placebo group (6 of 20 patients who returned for follow-up) and 18% (2 of 11 who returned) in the propranolol group. At 3 months, the CAPS scores did not differ. However, the psychophysiologic testing results suggested that propranolol had an impact. None of the 8 propranolol patients who participated, but 6 of the 14 participating placebo patients, were physiologic responders, reported Dr. Pitman and his associates (Biol. Psychiatry 2002;51:189–92).

In a second, nonrandomized study of patients treated in the emergency departments of two hospitals in France, 11 patients received propranolol for 7 days (40 mg three times daily), with the first dose administered 2–20 hours after the trauma and with a taper period of 8–12 days; they were compared with 8 patients who refused propranolol but agreed to participate.

PTSD rates, as well as PTSD symptom scores, were higher in the patients who refused the drug (3 of 8) than in patients who took it (1 of 11), reported Guillaume Vaiva, M.D., of the University of Lille (France), and his associates (Biol. Psychiatry 2003;54:947–9).

“The French study showed a significant reduction of PTSD symptoms—we only found a significant trend,” Dr. Pitman said.

Over the next several years, victims of car accidents, crimes, or other traumas treated at Boston's Massachusetts General Hospital will be offered a common heart drug—the β-adrenergic blocker propranolol—to potentially help lessen the intensity and impact of traumatic memories.

Participants in this study will be part of a wave of new drug trials aimed at intervening early to alter memory processes and prevent posttraumatic stress disorder (PTSD). Other studies are planned using later intervention to treat PTSD by affecting memory “reconsolidation,” the process by which memories that have been reactivated are stored again.

The study at Massachusetts General builds on a pilot study, published in 2002, that suggested that posttrauma administration of propranolol in the emergency room may have a “preventive effect” on subsequent PTSD. (See box.)

Roger Pitman, M.D., who led the pilot study and has a $2.5 million grant from the National Institutes of Mental Health to conduct the larger double-blind randomized study, hopes to recruit at least 100 patients who have experienced a traumatic event and present with tachycardia of at least 80 beats/min. According to Dr. Pittman, most studies addressing the issue of tachycardia as a predictor of PTSD “have been positive.”

Propranolol is commonly used to treat high blood pressure and for other cardiovascular purposes. It is also prescribed, albeit less frequently, as an antianxiety therapy adjunct for people with public speaking anxieties, fear of flying, and other phobias. It is the only β-blocker that can cross the blood-brain barrier, Dr. Pitman said.

Patients in his study will be randomized to receive, within 6 hours of the event, a 10-day course of placebo or propranolol followed by a 9-day taper period, said Dr. Pittman, professor of psychiatry at Harvard Medical School, Boston.

A major question faced by investigators concerns the timing of the memory consolidation processes. “We don't know what our window of opportunity is,” Dr. Pitman said. “In the most pessimistic estimate, it takes 30 minutes. And it takes at least 30 minutes for propranolol to be absorbed. Some data suggest, though, that the process may take 8 hours.”

Some physicians believe that it may be more feasible to intervene later and to work on memories that already have formed. The idea here is to reactivate or retrieve the memory and, while it is briefly vulnerable, attempt to weaken it before it is restored.

At the October meeting of the Society of Neuroscience, investigators from the Center for Neural Science at New York University presented preliminary findings that suggested propranolol at least partly disrupts the “reconsolidation” of fear memories, via the amygdala, significantly weakening the memories.

NYU physicians have begun working with others at the multi-institutional Center for the Neuroscience of Fear and Anxiety on testing whether propranolol helps PTSD patients who take it after recalling traumatic experiences.

Dr. Pitman also is planning a study with Karim Nader, Ph.D., a neuroscientist at McGill University in Montreal, in which they will reactivate traumatic memories of PTSD patients and measure the ability of propranolol to reduce the subsequent strength of the memories.

Other physicians have their eyes on the use of selective serotonin reuptake inhibitors (SSRIs) for PTSD prevention.

At Massachusetts General, Mark Pollack, M.D., is testing Lexapro (escitalopram) “at the next potential point of intervention”—in patients who, within a few weeks after trauma, are experiencing acute stress symptoms but do not meet the full criteria for PTSD.

The hope is that the drugs will help interrupt the cycle of increased arousal and anxiety that may presage full-blown PTSD, said Dr. Pollack, director of the hospital's Anxiety and Traumatic Stress Disorders Program. SSRIs are often used (with moderate success) to treat syndromal PTSD.

Physicians at the Center for the Study of Traumatic Stress at the Uniformed Health Services University of the Health Sciences in Bethesda, Md., have started a similar study, administering an SSRI to car accident victims days to several weeks after the event. Robert Ursano, M.D., who chairs the department of psychiatry at the university, is optimistic enough to say that “PTSD may be the first psychiatric illness that we–ll be able to prevent.”

Investigators are also encouraged by pharmacologic studies aimed at enhancing the process of fear extinction and making it a better adjunct to psychotherapy. One drug of interest is d-cycloserine, which enhances the activity of a protein in the amygdala that is important for fear extinction.

A recent study showed that patients with acrophobia who had exposure therapy combined with d-cycloserine had significantly larger reductions in their symptoms than patients who received placebo (Arch. Gen. Psychiatry 2004;61:1136–44).

Cycloserine could show similar effects for PTSD, said Michael Davis, Ph.D., professor of psychiatry and behavioral sciences at Emory University, Atlanta. “I–m not sure how good propranolol will be in the long run,” he said. “If you're trying to get rid of really traumatic fear memories, you need something to block not only the active recollection [of the event], but also the associated fear.

Small Studies of Propranolol Set Scene

Dr. Pitman's initial study of propranolol is one of two small pilot studies that looked at use of the drug shortly after a traumatic event.

Forty-one patients were randomized in the emergency department at Massachusetts General Hospital to begin—within 6 hours of a traumatic event—a 10-day course of propranolol (40 mg four times daily) or placebo. Eighteen of the 41 received propranolol.

Patients in the double-blind study were instructed to return 1 and 3 months later for assessment with the Clinician-Administered PTSD Scale (CAPS). At the 3-month follow-up, investigators also measured patients' physiologic responses during script-driven imagery of the traumatic event.

At 1 month, the PTSD rate was 30% in the placebo group (6 of 20 patients who returned for follow-up) and 18% (2 of 11 who returned) in the propranolol group. At 3 months, the CAPS scores did not differ. However, the psychophysiologic testing results suggested that propranolol had an impact. None of the 8 propranolol patients who participated, but 6 of the 14 participating placebo patients, were physiologic responders, reported Dr. Pitman and his associates (Biol. Psychiatry 2002;51:189–92).

In a second, nonrandomized study of patients treated in the emergency departments of two hospitals in France, 11 patients received propranolol for 7 days (40 mg three times daily), with the first dose administered 2–20 hours after the trauma and with a taper period of 8–12 days; they were compared with 8 patients who refused propranolol but agreed to participate.

PTSD rates, as well as PTSD symptom scores, were higher in the patients who refused the drug (3 of 8) than in patients who took it (1 of 11), reported Guillaume Vaiva, M.D., of the University of Lille (France), and his associates (Biol. Psychiatry 2003;54:947–9).

“The French study showed a significant reduction of PTSD symptoms—we only found a significant trend,” Dr. Pitman said.

Over the next several years, victims of car accidents, crimes, or other traumas treated at Boston's Massachusetts General Hospital will be offered a common heart drug—the β-adrenergic blocker propranolol—to potentially help lessen the intensity and impact of traumatic memories.

Participants in this study will be part of a wave of new drug trials aimed at intervening early to alter memory processes and prevent posttraumatic stress disorder (PTSD). Other studies are planned using later intervention to treat PTSD by affecting memory “reconsolidation,” the process by which memories that have been reactivated are stored again.

The study at Massachusetts General builds on a pilot study, published in 2002, that suggested that posttrauma administration of propranolol in the emergency room may have a “preventive effect” on subsequent PTSD. (See box.)

Roger Pitman, M.D., who led the pilot study and has a $2.5 million grant from the National Institutes of Mental Health to conduct the larger double-blind randomized study, hopes to recruit at least 100 patients who have experienced a traumatic event and present with tachycardia of at least 80 beats/min. According to Dr. Pittman, most studies addressing the issue of tachycardia as a predictor of PTSD “have been positive.”

Propranolol is commonly used to treat high blood pressure and for other cardiovascular purposes. It is also prescribed, albeit less frequently, as an antianxiety therapy adjunct for people with public speaking anxieties, fear of flying, and other phobias. It is the only β-blocker that can cross the blood-brain barrier, Dr. Pitman said.

Patients in his study will be randomized to receive, within 6 hours of the event, a 10-day course of placebo or propranolol followed by a 9-day taper period, said Dr. Pittman, professor of psychiatry at Harvard Medical School, Boston.

A major question faced by investigators concerns the timing of the memory consolidation processes. “We don't know what our window of opportunity is,” Dr. Pitman said. “In the most pessimistic estimate, it takes 30 minutes. And it takes at least 30 minutes for propranolol to be absorbed. Some data suggest, though, that the process may take 8 hours.”

Some physicians believe that it may be more feasible to intervene later and to work on memories that already have formed. The idea here is to reactivate or retrieve the memory and, while it is briefly vulnerable, attempt to weaken it before it is restored.

At the October meeting of the Society of Neuroscience, investigators from the Center for Neural Science at New York University presented preliminary findings that suggested propranolol at least partly disrupts the “reconsolidation” of fear memories, via the amygdala, significantly weakening the memories.

NYU physicians have begun working with others at the multi-institutional Center for the Neuroscience of Fear and Anxiety on testing whether propranolol helps PTSD patients who take it after recalling traumatic experiences.

Dr. Pitman also is planning a study with Karim Nader, Ph.D., a neuroscientist at McGill University in Montreal, in which they will reactivate traumatic memories of PTSD patients and measure the ability of propranolol to reduce the subsequent strength of the memories.

Other physicians have their eyes on the use of selective serotonin reuptake inhibitors (SSRIs) for PTSD prevention.

At Massachusetts General, Mark Pollack, M.D., is testing Lexapro (escitalopram) “at the next potential point of intervention”—in patients who, within a few weeks after trauma, are experiencing acute stress symptoms but do not meet the full criteria for PTSD.

The hope is that the drugs will help interrupt the cycle of increased arousal and anxiety that may presage full-blown PTSD, said Dr. Pollack, director of the hospital's Anxiety and Traumatic Stress Disorders Program. SSRIs are often used (with moderate success) to treat syndromal PTSD.

Physicians at the Center for the Study of Traumatic Stress at the Uniformed Health Services University of the Health Sciences in Bethesda, Md., have started a similar study, administering an SSRI to car accident victims days to several weeks after the event. Robert Ursano, M.D., who chairs the department of psychiatry at the university, is optimistic enough to say that “PTSD may be the first psychiatric illness that we–ll be able to prevent.”

Investigators are also encouraged by pharmacologic studies aimed at enhancing the process of fear extinction and making it a better adjunct to psychotherapy. One drug of interest is d-cycloserine, which enhances the activity of a protein in the amygdala that is important for fear extinction.

A recent study showed that patients with acrophobia who had exposure therapy combined with d-cycloserine had significantly larger reductions in their symptoms than patients who received placebo (Arch. Gen. Psychiatry 2004;61:1136–44).

Cycloserine could show similar effects for PTSD, said Michael Davis, Ph.D., professor of psychiatry and behavioral sciences at Emory University, Atlanta. “I–m not sure how good propranolol will be in the long run,” he said. “If you're trying to get rid of really traumatic fear memories, you need something to block not only the active recollection [of the event], but also the associated fear.

Small Studies of Propranolol Set Scene

Dr. Pitman's initial study of propranolol is one of two small pilot studies that looked at use of the drug shortly after a traumatic event.

Forty-one patients were randomized in the emergency department at Massachusetts General Hospital to begin—within 6 hours of a traumatic event—a 10-day course of propranolol (40 mg four times daily) or placebo. Eighteen of the 41 received propranolol.

Patients in the double-blind study were instructed to return 1 and 3 months later for assessment with the Clinician-Administered PTSD Scale (CAPS). At the 3-month follow-up, investigators also measured patients' physiologic responses during script-driven imagery of the traumatic event.

At 1 month, the PTSD rate was 30% in the placebo group (6 of 20 patients who returned for follow-up) and 18% (2 of 11 who returned) in the propranolol group. At 3 months, the CAPS scores did not differ. However, the psychophysiologic testing results suggested that propranolol had an impact. None of the 8 propranolol patients who participated, but 6 of the 14 participating placebo patients, were physiologic responders, reported Dr. Pitman and his associates (Biol. Psychiatry 2002;51:189–92).

In a second, nonrandomized study of patients treated in the emergency departments of two hospitals in France, 11 patients received propranolol for 7 days (40 mg three times daily), with the first dose administered 2–20 hours after the trauma and with a taper period of 8–12 days; they were compared with 8 patients who refused propranolol but agreed to participate.

PTSD rates, as well as PTSD symptom scores, were higher in the patients who refused the drug (3 of 8) than in patients who took it (1 of 11), reported Guillaume Vaiva, M.D., of the University of Lille (France), and his associates (Biol. Psychiatry 2003;54:947–9).

“The French study showed a significant reduction of PTSD symptoms—we only found a significant trend,” Dr. Pitman said.

Magnetic resonance imaging is superior to CT for detection of chronic brain hemorrhage and is its equal in confirming suspected acute intracerebral hemorrhage, judging from the findings of a prospective, multicenter study.

Many stroke centers currently obtain both MRI and CT in initial evaluations of suspected brain hemorrhage, a practice that is costly in both time and money. Given the new findings, MRI “may be acceptable as the sole imaging technique for acute stroke at centers with expertise,” reported Chelsea S. Kidwell, M.D., of the UCLA Stroke Center, and associates.

The findings of the Hemorrhage and Early MRI Evaluation (HEME) study also suggest that gradient recalled echo (GRE) MRI–in addition to detecting hyperacute and chronic hemorrhage–may be able to detect regions of hemorrhagic transformation of an acute ischemic stroke that are not evident on CT (JAMA 2004;292:1823–30).

The study was performed between 2000 and 2003 at two stroke centers. Patients in the study had a mean age of 75 years. Patients presenting with focal stroke symptoms within 6 hours of onset underwent brain GRE MRI followed by noncontrast CT. Scans were read by four blinded readers.

The findings complement another recently published study performed by the German Stroke Competence Network, which suggested that MRI is as accurate as CT for the detection of hyperacute hemorrhage (Stroke 2004;35:502–6).

In fact, when preliminary results of this other study became available, the HEME investigators performed an interim analysis of their own data and found that MRI was detecting acute hemorrhages not seen on CT. They stopped their own study early, after 200 patients were enrolled, to expedite their analysis.

The panel detected hemorrhage of any type in 71 patients with MRI and in 29 patients with CT. Acute hemorrhage specifically was diagnosed in 25 patients on both MRI and CT.

In four additional patients, however, acute hemorrhage was identified on the MRI but not on the corresponding CT. The panel interpreted each of these cases as hemorrhagic transformation of an ischemic infarct.

In three patients, regions interpreted as acute hemorrhage on CT were interpreted as chronic hemorrhage on MRI. In one patient, subarachnoid hemorrhage was diagnosed on CT but not on MRI. And in 49 patients, chronic hemorrhage, most often microbleeds, was seen on MRI but not on CT.

The investigators noted that it is unclear whether evidence of hemorrhagic transformation on MRI conveys a higher risk of symptomatic hemorrhage with thrombolytic treatment. The role of microbleeds in determining patient eligibility for thrombolytic therapy is also unknown, the investigators said.

An important caveat to the role of MRI, they noted, is that with small hemorrhages, blood that appears as acute on CT may appear as chronic on GRE MRI. “A noncontrast CT may be required to confirm the diagnosis in these cases,” they said.

Magnetic resonance imaging is superior to CT for detection of chronic brain hemorrhage and is its equal in confirming suspected acute intracerebral hemorrhage, judging from the findings of a prospective, multicenter study.

Many stroke centers currently obtain both MRI and CT in initial evaluations of suspected brain hemorrhage, a practice that is costly in both time and money. Given the new findings, MRI “may be acceptable as the sole imaging technique for acute stroke at centers with expertise,” reported Chelsea S. Kidwell, M.D., of the UCLA Stroke Center, and associates.

The findings of the Hemorrhage and Early MRI Evaluation (HEME) study also suggest that gradient recalled echo (GRE) MRI–in addition to detecting hyperacute and chronic hemorrhage–may be able to detect regions of hemorrhagic transformation of an acute ischemic stroke that are not evident on CT (JAMA 2004;292:1823–30).

The study was performed between 2000 and 2003 at two stroke centers. Patients in the study had a mean age of 75 years. Patients presenting with focal stroke symptoms within 6 hours of onset underwent brain GRE MRI followed by noncontrast CT. Scans were read by four blinded readers.

The findings complement another recently published study performed by the German Stroke Competence Network, which suggested that MRI is as accurate as CT for the detection of hyperacute hemorrhage (Stroke 2004;35:502–6).

In fact, when preliminary results of this other study became available, the HEME investigators performed an interim analysis of their own data and found that MRI was detecting acute hemorrhages not seen on CT. They stopped their own study early, after 200 patients were enrolled, to expedite their analysis.

The panel detected hemorrhage of any type in 71 patients with MRI and in 29 patients with CT. Acute hemorrhage specifically was diagnosed in 25 patients on both MRI and CT.

In four additional patients, however, acute hemorrhage was identified on the MRI but not on the corresponding CT. The panel interpreted each of these cases as hemorrhagic transformation of an ischemic infarct.

In three patients, regions interpreted as acute hemorrhage on CT were interpreted as chronic hemorrhage on MRI. In one patient, subarachnoid hemorrhage was diagnosed on CT but not on MRI. And in 49 patients, chronic hemorrhage, most often microbleeds, was seen on MRI but not on CT.

The investigators noted that it is unclear whether evidence of hemorrhagic transformation on MRI conveys a higher risk of symptomatic hemorrhage with thrombolytic treatment. The role of microbleeds in determining patient eligibility for thrombolytic therapy is also unknown, the investigators said.

An important caveat to the role of MRI, they noted, is that with small hemorrhages, blood that appears as acute on CT may appear as chronic on GRE MRI. “A noncontrast CT may be required to confirm the diagnosis in these cases,” they said.

Magnetic resonance imaging is superior to CT for detection of chronic brain hemorrhage and is its equal in confirming suspected acute intracerebral hemorrhage, judging from the findings of a prospective, multicenter study.

Many stroke centers currently obtain both MRI and CT in initial evaluations of suspected brain hemorrhage, a practice that is costly in both time and money. Given the new findings, MRI “may be acceptable as the sole imaging technique for acute stroke at centers with expertise,” reported Chelsea S. Kidwell, M.D., of the UCLA Stroke Center, and associates.

The findings of the Hemorrhage and Early MRI Evaluation (HEME) study also suggest that gradient recalled echo (GRE) MRI–in addition to detecting hyperacute and chronic hemorrhage–may be able to detect regions of hemorrhagic transformation of an acute ischemic stroke that are not evident on CT (JAMA 2004;292:1823–30).

The study was performed between 2000 and 2003 at two stroke centers. Patients in the study had a mean age of 75 years. Patients presenting with focal stroke symptoms within 6 hours of onset underwent brain GRE MRI followed by noncontrast CT. Scans were read by four blinded readers.

The findings complement another recently published study performed by the German Stroke Competence Network, which suggested that MRI is as accurate as CT for the detection of hyperacute hemorrhage (Stroke 2004;35:502–6).

In fact, when preliminary results of this other study became available, the HEME investigators performed an interim analysis of their own data and found that MRI was detecting acute hemorrhages not seen on CT. They stopped their own study early, after 200 patients were enrolled, to expedite their analysis.

The panel detected hemorrhage of any type in 71 patients with MRI and in 29 patients with CT. Acute hemorrhage specifically was diagnosed in 25 patients on both MRI and CT.

In four additional patients, however, acute hemorrhage was identified on the MRI but not on the corresponding CT. The panel interpreted each of these cases as hemorrhagic transformation of an ischemic infarct.

In three patients, regions interpreted as acute hemorrhage on CT were interpreted as chronic hemorrhage on MRI. In one patient, subarachnoid hemorrhage was diagnosed on CT but not on MRI. And in 49 patients, chronic hemorrhage, most often microbleeds, was seen on MRI but not on CT.

The investigators noted that it is unclear whether evidence of hemorrhagic transformation on MRI conveys a higher risk of symptomatic hemorrhage with thrombolytic treatment. The role of microbleeds in determining patient eligibility for thrombolytic therapy is also unknown, the investigators said.

An important caveat to the role of MRI, they noted, is that with small hemorrhages, blood that appears as acute on CT may appear as chronic on GRE MRI. “A noncontrast CT may be required to confirm the diagnosis in these cases,” they said.

Current guidelines on the use of thrombolytic therapy for acute ischemic stroke are “hopelessly outdated,” Louis R. Caplan, M.D., said in an editorial that accompanied several reports of patient outcomes studies published in the Journal of the American Medical Association.

The guidelines, which are nearly a decade old, exclude from thrombolytic therapy patients who may indeed benefit from it and do not consider the major advances in diagnostic technology that have occurred over the past 2 decades, said Dr. Caplan, chief of the division of cerebrovascular diseases at Beth Israel Deaconess Medical Center in Boston.

The results of two recent studies on outcomes after thrombolysis are “an important reminder” that few patients with ischemic stroke receive thrombolytic therapy, according to Dr. Caplan (JAMA 2004;292:1883–5).

On the other hand, this treatment “is not a panacea and may actually cause intracerebral hemorrhage or death” in some patients, said Dr. Caplan, who is also professor of neurology at Harvard Medical School, Boston.

In a study by the German Stroke Registers Study Group on predictors of in-hospital mortality after thrombolysis, only 3% of almost 60,000 patients presenting with acute stroke received intravenous tissue plasminogen activator (tPA). Of treated patients, 10% died during hospitalization.

In the second study, more than half (51%) of 216 patients treated with alteplase in London, Ont., failed to improve significantly after treatment when the published guidelines were followed.

Neither study reported causative vascular lesions, or the extent of infarction before or after treatment–information that can be identified with modern imaging techniques, Dr. Caplan noted.

“If the present guidelines continue to be followed, as in the [two studies], physicians will never know which patients with what degree of infarction and with what vascular lesions and at-risk tissue will benefit from thrombolysis,” he said.

Nor will physicians know “whether intravenous, intraarterial, or combined intravenous and intraarterial [therapies] are best and in what circumstances,” Dr. Caplan said. “Clinicians also will not know how alteplase compares with other promising newer thrombolytic agents and, possibly, with other therapies.”

In the German study–a prospective, observational cohort study conducted at 225 community and academic hospitals throughout Germany–investigators reported that the factors predicting in-hospital death after thrombolytic therapy were decreased level of consciousness (an odds ratio of 3.5) and older age (an adjusted odds ratio of 1.6 for each 10-year increment of age). Each factor independently increased the risk of death, said Peter U. Heuschmann, M.D., of the University of Münster (Germany), and his associates (JAMA 2004;292:1831–8).

The overall rate of symptomatic intracranial hemorrhage was 7% and increased with age. One or more serious complications occurred in 27% of all patients and 84% of those who died after treatment.

In the Ontario study–a prospective study of acute stroke patients who received alteplase at a university hospital over 4 years–investigators reported that a lack of improvement at 24 hours was associated with poor outcome and death at 3 months. At 3 months, 20% of patients had died.

They identified three factors–elevated baseline glucose level (144 mg/dL), cortical involvement, and time to thrombolytic therapy–that predicted a lack of improvement at 24 hours. For each 5-minute increase in the time that elapsed from symptom onset to treatment, the chance of no improvement increased by 5%, said Gustavo Saposnik, M.D., of the London Health Sciences Centre, and his associates (JAMA 2004;292:1839–44).

In his editorial, Dr. Caplan said that although earlier treatment is better, studies show that the mandated 3-hour time window for thrombolytic therapy may not be appropriate.

“Patients with stroke do not become poor candidates for alteplase when the clock strikes 4 hours,” he said.

Dr. Caplan cautioned against “cookbook guidelines” and explained that treatment decisions must utilize modern diagnostic technology and be individually focused on “each given patient with a given lesion and a known extent of infarction.”

There is also an urgent need for more qualified stroke centers, more experienced stroke clinicians, and new ways to get patients to the centers quickly, he said.

Current guidelines on the use of thrombolytic therapy for acute ischemic stroke are “hopelessly outdated,” Louis R. Caplan, M.D., said in an editorial that accompanied several reports of patient outcomes studies published in the Journal of the American Medical Association.

The guidelines, which are nearly a decade old, exclude from thrombolytic therapy patients who may indeed benefit from it and do not consider the major advances in diagnostic technology that have occurred over the past 2 decades, said Dr. Caplan, chief of the division of cerebrovascular diseases at Beth Israel Deaconess Medical Center in Boston.

The results of two recent studies on outcomes after thrombolysis are “an important reminder” that few patients with ischemic stroke receive thrombolytic therapy, according to Dr. Caplan (JAMA 2004;292:1883–5).

On the other hand, this treatment “is not a panacea and may actually cause intracerebral hemorrhage or death” in some patients, said Dr. Caplan, who is also professor of neurology at Harvard Medical School, Boston.

In a study by the German Stroke Registers Study Group on predictors of in-hospital mortality after thrombolysis, only 3% of almost 60,000 patients presenting with acute stroke received intravenous tissue plasminogen activator (tPA). Of treated patients, 10% died during hospitalization.

In the second study, more than half (51%) of 216 patients treated with alteplase in London, Ont., failed to improve significantly after treatment when the published guidelines were followed.

Neither study reported causative vascular lesions, or the extent of infarction before or after treatment–information that can be identified with modern imaging techniques, Dr. Caplan noted.

“If the present guidelines continue to be followed, as in the [two studies], physicians will never know which patients with what degree of infarction and with what vascular lesions and at-risk tissue will benefit from thrombolysis,” he said.

Nor will physicians know “whether intravenous, intraarterial, or combined intravenous and intraarterial [therapies] are best and in what circumstances,” Dr. Caplan said. “Clinicians also will not know how alteplase compares with other promising newer thrombolytic agents and, possibly, with other therapies.”

In the German study–a prospective, observational cohort study conducted at 225 community and academic hospitals throughout Germany–investigators reported that the factors predicting in-hospital death after thrombolytic therapy were decreased level of consciousness (an odds ratio of 3.5) and older age (an adjusted odds ratio of 1.6 for each 10-year increment of age). Each factor independently increased the risk of death, said Peter U. Heuschmann, M.D., of the University of Münster (Germany), and his associates (JAMA 2004;292:1831–8).

The overall rate of symptomatic intracranial hemorrhage was 7% and increased with age. One or more serious complications occurred in 27% of all patients and 84% of those who died after treatment.

In the Ontario study–a prospective study of acute stroke patients who received alteplase at a university hospital over 4 years–investigators reported that a lack of improvement at 24 hours was associated with poor outcome and death at 3 months. At 3 months, 20% of patients had died.

They identified three factors–elevated baseline glucose level (144 mg/dL), cortical involvement, and time to thrombolytic therapy–that predicted a lack of improvement at 24 hours. For each 5-minute increase in the time that elapsed from symptom onset to treatment, the chance of no improvement increased by 5%, said Gustavo Saposnik, M.D., of the London Health Sciences Centre, and his associates (JAMA 2004;292:1839–44).

In his editorial, Dr. Caplan said that although earlier treatment is better, studies show that the mandated 3-hour time window for thrombolytic therapy may not be appropriate.

“Patients with stroke do not become poor candidates for alteplase when the clock strikes 4 hours,” he said.

Dr. Caplan cautioned against “cookbook guidelines” and explained that treatment decisions must utilize modern diagnostic technology and be individually focused on “each given patient with a given lesion and a known extent of infarction.”

There is also an urgent need for more qualified stroke centers, more experienced stroke clinicians, and new ways to get patients to the centers quickly, he said.

Current guidelines on the use of thrombolytic therapy for acute ischemic stroke are “hopelessly outdated,” Louis R. Caplan, M.D., said in an editorial that accompanied several reports of patient outcomes studies published in the Journal of the American Medical Association.

The guidelines, which are nearly a decade old, exclude from thrombolytic therapy patients who may indeed benefit from it and do not consider the major advances in diagnostic technology that have occurred over the past 2 decades, said Dr. Caplan, chief of the division of cerebrovascular diseases at Beth Israel Deaconess Medical Center in Boston.

The results of two recent studies on outcomes after thrombolysis are “an important reminder” that few patients with ischemic stroke receive thrombolytic therapy, according to Dr. Caplan (JAMA 2004;292:1883–5).

On the other hand, this treatment “is not a panacea and may actually cause intracerebral hemorrhage or death” in some patients, said Dr. Caplan, who is also professor of neurology at Harvard Medical School, Boston.

In a study by the German Stroke Registers Study Group on predictors of in-hospital mortality after thrombolysis, only 3% of almost 60,000 patients presenting with acute stroke received intravenous tissue plasminogen activator (tPA). Of treated patients, 10% died during hospitalization.

In the second study, more than half (51%) of 216 patients treated with alteplase in London, Ont., failed to improve significantly after treatment when the published guidelines were followed.

Neither study reported causative vascular lesions, or the extent of infarction before or after treatment–information that can be identified with modern imaging techniques, Dr. Caplan noted.

“If the present guidelines continue to be followed, as in the [two studies], physicians will never know which patients with what degree of infarction and with what vascular lesions and at-risk tissue will benefit from thrombolysis,” he said.

Nor will physicians know “whether intravenous, intraarterial, or combined intravenous and intraarterial [therapies] are best and in what circumstances,” Dr. Caplan said. “Clinicians also will not know how alteplase compares with other promising newer thrombolytic agents and, possibly, with other therapies.”

In the German study–a prospective, observational cohort study conducted at 225 community and academic hospitals throughout Germany–investigators reported that the factors predicting in-hospital death after thrombolytic therapy were decreased level of consciousness (an odds ratio of 3.5) and older age (an adjusted odds ratio of 1.6 for each 10-year increment of age). Each factor independently increased the risk of death, said Peter U. Heuschmann, M.D., of the University of Münster (Germany), and his associates (JAMA 2004;292:1831–8).

The overall rate of symptomatic intracranial hemorrhage was 7% and increased with age. One or more serious complications occurred in 27% of all patients and 84% of those who died after treatment.

In the Ontario study–a prospective study of acute stroke patients who received alteplase at a university hospital over 4 years–investigators reported that a lack of improvement at 24 hours was associated with poor outcome and death at 3 months. At 3 months, 20% of patients had died.

They identified three factors–elevated baseline glucose level (144 mg/dL), cortical involvement, and time to thrombolytic therapy–that predicted a lack of improvement at 24 hours. For each 5-minute increase in the time that elapsed from symptom onset to treatment, the chance of no improvement increased by 5%, said Gustavo Saposnik, M.D., of the London Health Sciences Centre, and his associates (JAMA 2004;292:1839–44).

In his editorial, Dr. Caplan said that although earlier treatment is better, studies show that the mandated 3-hour time window for thrombolytic therapy may not be appropriate.

“Patients with stroke do not become poor candidates for alteplase when the clock strikes 4 hours,” he said.

Dr. Caplan cautioned against “cookbook guidelines” and explained that treatment decisions must utilize modern diagnostic technology and be individually focused on “each given patient with a given lesion and a known extent of infarction.”

There is also an urgent need for more qualified stroke centers, more experienced stroke clinicians, and new ways to get patients to the centers quickly, he said.

Magnetic resonance imaging is superior to CT for detection of chronic brain hemorrhage and is its equal in confirming suspected acute intracerebral hemorrhage, judging from the findings of a prospective, multicenter study.

Many stroke centers currently obtain both MRI and CT in initial evaluations of suspected brain hemorrhage, a practice that is costly in both time and money. Given the new findings, MRI “may be acceptable as the sole imaging technique for acute stroke at centers with expertise,” reported Chelsea S. Kidwell, M.D., of the UCLA Stroke Center, and associates.

Noncontrast CT has been the standard brain imaging study for the initial evaluation of patients with stroke, but interest in multimodal MRI—and its potential ability to distinguish hemorrhage from cerebral ischemia—has been building.

The findings of the Hemorrhage and Early MRI Evaluation (HEME) study also suggest that gradient recalled echo (GRE) MRI—in addition to detecting hyperacute and chronic hemorrhage—may be able to detect regions of hemorrhagic transformation of an acute ischemic stroke that are not evident on CT (JAMA 2004;292:1823–30).

The study was performed between 2000 and 2003 at two stroke centers—UCLA Stroke Center in Los Angeles and Suburban Hospital in Bethesda, Md. Patients presenting with focal stroke symptoms within 6 hours of onset underwent brain GRE MRI followed by noncontrast CT. Scans were read by four blinded readers.

The findings complement another recently published study performed by the German Stroke Competence Network, which suggested that MRI is as accurate as CT for the detection of hyperacute hemorrhage (Stroke 2004;35:502–6).

In fact, when preliminary results of this other study became available, the HEME investigators performed an interim analysis of their own data and found that MRI was detecting acute hemorrhages not seen on CT. They stopped their own study early, after 200 patients were enrolled, to expedite their analysis.

The panel detected hemorrhage of any type in 71 patients with MRI and in 29 patients with CT. Acute hemorrhage specifically was diagnosed in 25 patients on both MRI and CT.

In four additional patients, however, acute hemorrhage was identified on the MRI but not on the corresponding CT. The panel interpreted each of these cases as hemorrhagic transformation of an ischemic infarct.

In three patients, regions interpreted as acute hemorrhage on CT were interpreted as chronic hemorrhage on MRI. In one patient, subarachnoid hemorrhage was diagnosed on CT but not on MRI. And in 49 patients, chronic hemorrhage, most often microbleeds, was seen on MRI but not CT.

In an accompanying editorial, Louis R. Caplan, M.D., of Beth Israel Deaconess Medical Center, Boston, said that results of this and other studies indicate that “for diagnosis of acute stroke, CT is not needed if a medical center has rapid access to modern MRI” (JAMA 2004;292:1883–5).

The investigators noted that it is unclear whether evidence of hemorrhagic transformation on MRI conveys a higher risk of symptomatic hemorrhage with thrombolytic treatment. The role of microbleeds in determining patient eligibility for thrombolytic therapy is also unknown, the investigators said.

An important caveat to the role of MRI, they noted, is that with small hemorrhages, blood that appears as acute on CT may appear as chronic on GRE MRI. “A noncontrast CT may be required to confirm the diagnosis in these cases,” they said.

Patients in the study had a mean age of 75 years. The median times to MRI and to CT were approximately 2 and 3 hours after symptom onset, respectively. The MRI stroke protocol generally took 10–15 minutes—timing that should allay concerns about the length of MRI's image acquisition time, they reported.

Magnetic resonance imaging is superior to CT for detection of chronic brain hemorrhage and is its equal in confirming suspected acute intracerebral hemorrhage, judging from the findings of a prospective, multicenter study.

Many stroke centers currently obtain both MRI and CT in initial evaluations of suspected brain hemorrhage, a practice that is costly in both time and money. Given the new findings, MRI “may be acceptable as the sole imaging technique for acute stroke at centers with expertise,” reported Chelsea S. Kidwell, M.D., of the UCLA Stroke Center, and associates.

Noncontrast CT has been the standard brain imaging study for the initial evaluation of patients with stroke, but interest in multimodal MRI—and its potential ability to distinguish hemorrhage from cerebral ischemia—has been building.

The findings of the Hemorrhage and Early MRI Evaluation (HEME) study also suggest that gradient recalled echo (GRE) MRI—in addition to detecting hyperacute and chronic hemorrhage—may be able to detect regions of hemorrhagic transformation of an acute ischemic stroke that are not evident on CT (JAMA 2004;292:1823–30).

The study was performed between 2000 and 2003 at two stroke centers—UCLA Stroke Center in Los Angeles and Suburban Hospital in Bethesda, Md. Patients presenting with focal stroke symptoms within 6 hours of onset underwent brain GRE MRI followed by noncontrast CT. Scans were read by four blinded readers.

The findings complement another recently published study performed by the German Stroke Competence Network, which suggested that MRI is as accurate as CT for the detection of hyperacute hemorrhage (Stroke 2004;35:502–6).

In fact, when preliminary results of this other study became available, the HEME investigators performed an interim analysis of their own data and found that MRI was detecting acute hemorrhages not seen on CT. They stopped their own study early, after 200 patients were enrolled, to expedite their analysis.

The panel detected hemorrhage of any type in 71 patients with MRI and in 29 patients with CT. Acute hemorrhage specifically was diagnosed in 25 patients on both MRI and CT.

In four additional patients, however, acute hemorrhage was identified on the MRI but not on the corresponding CT. The panel interpreted each of these cases as hemorrhagic transformation of an ischemic infarct.

In three patients, regions interpreted as acute hemorrhage on CT were interpreted as chronic hemorrhage on MRI. In one patient, subarachnoid hemorrhage was diagnosed on CT but not on MRI. And in 49 patients, chronic hemorrhage, most often microbleeds, was seen on MRI but not CT.

In an accompanying editorial, Louis R. Caplan, M.D., of Beth Israel Deaconess Medical Center, Boston, said that results of this and other studies indicate that “for diagnosis of acute stroke, CT is not needed if a medical center has rapid access to modern MRI” (JAMA 2004;292:1883–5).

The investigators noted that it is unclear whether evidence of hemorrhagic transformation on MRI conveys a higher risk of symptomatic hemorrhage with thrombolytic treatment. The role of microbleeds in determining patient eligibility for thrombolytic therapy is also unknown, the investigators said.

An important caveat to the role of MRI, they noted, is that with small hemorrhages, blood that appears as acute on CT may appear as chronic on GRE MRI. “A noncontrast CT may be required to confirm the diagnosis in these cases,” they said.

Patients in the study had a mean age of 75 years. The median times to MRI and to CT were approximately 2 and 3 hours after symptom onset, respectively. The MRI stroke protocol generally took 10–15 minutes—timing that should allay concerns about the length of MRI's image acquisition time, they reported.

Magnetic resonance imaging is superior to CT for detection of chronic brain hemorrhage and is its equal in confirming suspected acute intracerebral hemorrhage, judging from the findings of a prospective, multicenter study.

Many stroke centers currently obtain both MRI and CT in initial evaluations of suspected brain hemorrhage, a practice that is costly in both time and money. Given the new findings, MRI “may be acceptable as the sole imaging technique for acute stroke at centers with expertise,” reported Chelsea S. Kidwell, M.D., of the UCLA Stroke Center, and associates.

Noncontrast CT has been the standard brain imaging study for the initial evaluation of patients with stroke, but interest in multimodal MRI—and its potential ability to distinguish hemorrhage from cerebral ischemia—has been building.

The findings of the Hemorrhage and Early MRI Evaluation (HEME) study also suggest that gradient recalled echo (GRE) MRI—in addition to detecting hyperacute and chronic hemorrhage—may be able to detect regions of hemorrhagic transformation of an acute ischemic stroke that are not evident on CT (JAMA 2004;292:1823–30).

The study was performed between 2000 and 2003 at two stroke centers—UCLA Stroke Center in Los Angeles and Suburban Hospital in Bethesda, Md. Patients presenting with focal stroke symptoms within 6 hours of onset underwent brain GRE MRI followed by noncontrast CT. Scans were read by four blinded readers.

The findings complement another recently published study performed by the German Stroke Competence Network, which suggested that MRI is as accurate as CT for the detection of hyperacute hemorrhage (Stroke 2004;35:502–6).

In fact, when preliminary results of this other study became available, the HEME investigators performed an interim analysis of their own data and found that MRI was detecting acute hemorrhages not seen on CT. They stopped their own study early, after 200 patients were enrolled, to expedite their analysis.

The panel detected hemorrhage of any type in 71 patients with MRI and in 29 patients with CT. Acute hemorrhage specifically was diagnosed in 25 patients on both MRI and CT.

In four additional patients, however, acute hemorrhage was identified on the MRI but not on the corresponding CT. The panel interpreted each of these cases as hemorrhagic transformation of an ischemic infarct.

In three patients, regions interpreted as acute hemorrhage on CT were interpreted as chronic hemorrhage on MRI. In one patient, subarachnoid hemorrhage was diagnosed on CT but not on MRI. And in 49 patients, chronic hemorrhage, most often microbleeds, was seen on MRI but not CT.

In an accompanying editorial, Louis R. Caplan, M.D., of Beth Israel Deaconess Medical Center, Boston, said that results of this and other studies indicate that “for diagnosis of acute stroke, CT is not needed if a medical center has rapid access to modern MRI” (JAMA 2004;292:1883–5).

The investigators noted that it is unclear whether evidence of hemorrhagic transformation on MRI conveys a higher risk of symptomatic hemorrhage with thrombolytic treatment. The role of microbleeds in determining patient eligibility for thrombolytic therapy is also unknown, the investigators said.

An important caveat to the role of MRI, they noted, is that with small hemorrhages, blood that appears as acute on CT may appear as chronic on GRE MRI. “A noncontrast CT may be required to confirm the diagnosis in these cases,” they said.

Patients in the study had a mean age of 75 years. The median times to MRI and to CT were approximately 2 and 3 hours after symptom onset, respectively. The MRI stroke protocol generally took 10–15 minutes—timing that should allay concerns about the length of MRI's image acquisition time, they reported.

Most low-grade abnormalities on Pap smears spontaneously regressed within 36 months in a cohort study of adolescents and young women, and study investigators say the finding lends support to the practice of monitoring these lesions with regular cytology.

Colposcopy is “unwarranted and leads to unnecessary intervention, morbidity, and cost,” said Anna-Barbara Moscicki, M.D., and her associates at the University of California, San Francisco.

Of 187 patients aged 13-22 years who developed low-grade squamous intraepithelial lesions (LSIL), 61% were free of LSIL after 1 year, and 91% were free of LSIL at 3 years' follow-up.

Progression to high-grade disease occurred in 3% of the patients (Lancet 2004;364:1678-83).

The patients were part of a larger 10-year longitudinal study of human papilloma virus (HPV) infection.

The women were examined every 4 months by cytology, colposcopy, and HPV DNA status. Both prevalent and incident LSIL cases were included in the study, and regression was defined as having at least three consecutive normal Pap smears.

The investigators found no associations between LSIL regression and HPV status at baseline (time of the first LSIL), age, sexual behavior, contraceptive use, substance or cigarette use, or incident sexually transmitted infection.

Nor did they find any significant differences in rates or timing of regression between patients who underwent biopsy and those who didn't, nor between patients whose LSIL status was confirmed by histology and those with LSIL confirmed by a normal biopsy.

The investigators did find that patients' current HPV status—rather than their baseline status—was important. A negative HPV test at a subsequent visit “shows a good likelihood that LSIL has regressed,” which suggests that HPV testing “could be helpful in monitoring LSIL,” they said.

In addition, the findings suggest that the persistence of multiple HPV types slows rates of regression, but this needs to be examined more closely. More study is also needed to better define appropriate screening strategies, Dr. Moscicki and her associates said.

The findings are similar to those of a smaller study from Brazil, published in 2003 in the Journal of the National Cancer Institute, in which an estimated 92%-95% of cases regressed within 24 months, and 5%-6% progressed, according to Anne Szarewski and Peter Sasieni of Cancer Research UK.

“It is becoming increasingly clear that LSIL is a transient manifestation of HPV infection that will only rarely progress to HSIL,” they wrote in an accompanying editorial (Lancet [in press]). “Since there is no point in treating LSIL in young women … we see absolutely no role for colposcopy in adolescents as part of routine management,” they concluded.

Most low-grade abnormalities on Pap smears spontaneously regressed within 36 months in a cohort study of adolescents and young women, and study investigators say the finding lends support to the practice of monitoring these lesions with regular cytology.

Colposcopy is “unwarranted and leads to unnecessary intervention, morbidity, and cost,” said Anna-Barbara Moscicki, M.D., and her associates at the University of California, San Francisco.

Of 187 patients aged 13-22 years who developed low-grade squamous intraepithelial lesions (LSIL), 61% were free of LSIL after 1 year, and 91% were free of LSIL at 3 years' follow-up.

Progression to high-grade disease occurred in 3% of the patients (Lancet 2004;364:1678-83).

The patients were part of a larger 10-year longitudinal study of human papilloma virus (HPV) infection.

The women were examined every 4 months by cytology, colposcopy, and HPV DNA status. Both prevalent and incident LSIL cases were included in the study, and regression was defined as having at least three consecutive normal Pap smears.

The investigators found no associations between LSIL regression and HPV status at baseline (time of the first LSIL), age, sexual behavior, contraceptive use, substance or cigarette use, or incident sexually transmitted infection.

Nor did they find any significant differences in rates or timing of regression between patients who underwent biopsy and those who didn't, nor between patients whose LSIL status was confirmed by histology and those with LSIL confirmed by a normal biopsy.

The investigators did find that patients' current HPV status—rather than their baseline status—was important. A negative HPV test at a subsequent visit “shows a good likelihood that LSIL has regressed,” which suggests that HPV testing “could be helpful in monitoring LSIL,” they said.

In addition, the findings suggest that the persistence of multiple HPV types slows rates of regression, but this needs to be examined more closely. More study is also needed to better define appropriate screening strategies, Dr. Moscicki and her associates said.

The findings are similar to those of a smaller study from Brazil, published in 2003 in the Journal of the National Cancer Institute, in which an estimated 92%-95% of cases regressed within 24 months, and 5%-6% progressed, according to Anne Szarewski and Peter Sasieni of Cancer Research UK.

“It is becoming increasingly clear that LSIL is a transient manifestation of HPV infection that will only rarely progress to HSIL,” they wrote in an accompanying editorial (Lancet [in press]). “Since there is no point in treating LSIL in young women … we see absolutely no role for colposcopy in adolescents as part of routine management,” they concluded.

Most low-grade abnormalities on Pap smears spontaneously regressed within 36 months in a cohort study of adolescents and young women, and study investigators say the finding lends support to the practice of monitoring these lesions with regular cytology.

Colposcopy is “unwarranted and leads to unnecessary intervention, morbidity, and cost,” said Anna-Barbara Moscicki, M.D., and her associates at the University of California, San Francisco.

Of 187 patients aged 13-22 years who developed low-grade squamous intraepithelial lesions (LSIL), 61% were free of LSIL after 1 year, and 91% were free of LSIL at 3 years' follow-up.

Progression to high-grade disease occurred in 3% of the patients (Lancet 2004;364:1678-83).

The patients were part of a larger 10-year longitudinal study of human papilloma virus (HPV) infection.

The women were examined every 4 months by cytology, colposcopy, and HPV DNA status. Both prevalent and incident LSIL cases were included in the study, and regression was defined as having at least three consecutive normal Pap smears.

The investigators found no associations between LSIL regression and HPV status at baseline (time of the first LSIL), age, sexual behavior, contraceptive use, substance or cigarette use, or incident sexually transmitted infection.

Nor did they find any significant differences in rates or timing of regression between patients who underwent biopsy and those who didn't, nor between patients whose LSIL status was confirmed by histology and those with LSIL confirmed by a normal biopsy.

The investigators did find that patients' current HPV status—rather than their baseline status—was important. A negative HPV test at a subsequent visit “shows a good likelihood that LSIL has regressed,” which suggests that HPV testing “could be helpful in monitoring LSIL,” they said.

In addition, the findings suggest that the persistence of multiple HPV types slows rates of regression, but this needs to be examined more closely. More study is also needed to better define appropriate screening strategies, Dr. Moscicki and her associates said.

The findings are similar to those of a smaller study from Brazil, published in 2003 in the Journal of the National Cancer Institute, in which an estimated 92%-95% of cases regressed within 24 months, and 5%-6% progressed, according to Anne Szarewski and Peter Sasieni of Cancer Research UK.

“It is becoming increasingly clear that LSIL is a transient manifestation of HPV infection that will only rarely progress to HSIL,” they wrote in an accompanying editorial (Lancet [in press]). “Since there is no point in treating LSIL in young women … we see absolutely no role for colposcopy in adolescents as part of routine management,” they concluded.

Most low-grade abnormalities on Pap smears spontaneously regressed within 36 months in a cohort study of adolescents and young women, and investigators say the finding lends support to the practice of monitoring these lesions with regular cytology.

Colposcopy is “unwarranted and leads to unnecessary intervention, morbidity, and cost,” said Anna-Barbara Moscicki, M.D., and her associates at the University of California, San Francisco.

Of 187 patients aged 13–22 years who developed low-grade squamous intraepithelial lesions (LSIL), 61% were free of LSIL after 1 year, and 91% were free of LSIL at 3 years' follow-up. Progression to high-grade disease occurred in 3% of the patients (Lancet 2004;364:1678–83).

The patients were part of a larger 10-year longitudinal study of human papilloma virus (HPV) infection. They were examined every 4 months by cytology, colposcopy, and HPV DNA status. Both prevalent and incident LSIL cases were included in the study, and regression was defined as at least three consecutive normal smears.

The investigators found no associations between LSIL regression and HPV status at baseline (time of the first LSIL), age, sexual behavior, contraceptive use, substance or cigarette use, or incident sexually transmitted infection.

Nor did they find any significant differences in rates or timing of regression between patients who underwent biopsy and those who didn't, nor between patients whose LSIL status was confirmed by histology and those with LSIL confirmed by a normal biopsy.

The investigators did find that patients' current HPV status—rather than their baseline status—was important. A negative HPV test at a subsequent visit “shows a good likelihood that LSIL has regressed,” which suggests that HPV testing “could be helpful in monitoring LSIL,” they said.

In addition, the findings suggest that the persistence of multiple HPV types slows rates of regression, but this needs to be examined more closely. More study is also needed to better define appropriate screening strategies, they said.

The findings are similar to those of a smaller study from Brazil, published in 2003 in the Journal of the National Cancer Institute, in which an estimated 92–95% of cases regressed within 24 months, and 5–6 % progressed, according to Anne Szarewski and Peter Sasieni of Cancer Research UK.

“It is becoming increasingly clear that LSIL is a transient manifestation of HPV infection that will only rarely progress to HSIL,” they wrote in an accompanying editorial (Lancet [in press]). “Since there is no point in treating LSIL in young women … we see absolutely no role for colposcopy in adolescents as part of routine management.”

Most low-grade abnormalities on Pap smears spontaneously regressed within 36 months in a cohort study of adolescents and young women, and investigators say the finding lends support to the practice of monitoring these lesions with regular cytology.

Colposcopy is “unwarranted and leads to unnecessary intervention, morbidity, and cost,” said Anna-Barbara Moscicki, M.D., and her associates at the University of California, San Francisco.

Of 187 patients aged 13–22 years who developed low-grade squamous intraepithelial lesions (LSIL), 61% were free of LSIL after 1 year, and 91% were free of LSIL at 3 years' follow-up. Progression to high-grade disease occurred in 3% of the patients (Lancet 2004;364:1678–83).

The patients were part of a larger 10-year longitudinal study of human papilloma virus (HPV) infection. They were examined every 4 months by cytology, colposcopy, and HPV DNA status. Both prevalent and incident LSIL cases were included in the study, and regression was defined as at least three consecutive normal smears.

The investigators found no associations between LSIL regression and HPV status at baseline (time of the first LSIL), age, sexual behavior, contraceptive use, substance or cigarette use, or incident sexually transmitted infection.

Nor did they find any significant differences in rates or timing of regression between patients who underwent biopsy and those who didn't, nor between patients whose LSIL status was confirmed by histology and those with LSIL confirmed by a normal biopsy.

The investigators did find that patients' current HPV status—rather than their baseline status—was important. A negative HPV test at a subsequent visit “shows a good likelihood that LSIL has regressed,” which suggests that HPV testing “could be helpful in monitoring LSIL,” they said.

In addition, the findings suggest that the persistence of multiple HPV types slows rates of regression, but this needs to be examined more closely. More study is also needed to better define appropriate screening strategies, they said.

The findings are similar to those of a smaller study from Brazil, published in 2003 in the Journal of the National Cancer Institute, in which an estimated 92–95% of cases regressed within 24 months, and 5–6 % progressed, according to Anne Szarewski and Peter Sasieni of Cancer Research UK.

“It is becoming increasingly clear that LSIL is a transient manifestation of HPV infection that will only rarely progress to HSIL,” they wrote in an accompanying editorial (Lancet [in press]). “Since there is no point in treating LSIL in young women … we see absolutely no role for colposcopy in adolescents as part of routine management.”

Most low-grade abnormalities on Pap smears spontaneously regressed within 36 months in a cohort study of adolescents and young women, and investigators say the finding lends support to the practice of monitoring these lesions with regular cytology.

Colposcopy is “unwarranted and leads to unnecessary intervention, morbidity, and cost,” said Anna-Barbara Moscicki, M.D., and her associates at the University of California, San Francisco.

Of 187 patients aged 13–22 years who developed low-grade squamous intraepithelial lesions (LSIL), 61% were free of LSIL after 1 year, and 91% were free of LSIL at 3 years' follow-up. Progression to high-grade disease occurred in 3% of the patients (Lancet 2004;364:1678–83).

The patients were part of a larger 10-year longitudinal study of human papilloma virus (HPV) infection. They were examined every 4 months by cytology, colposcopy, and HPV DNA status. Both prevalent and incident LSIL cases were included in the study, and regression was defined as at least three consecutive normal smears.

The investigators found no associations between LSIL regression and HPV status at baseline (time of the first LSIL), age, sexual behavior, contraceptive use, substance or cigarette use, or incident sexually transmitted infection.

Nor did they find any significant differences in rates or timing of regression between patients who underwent biopsy and those who didn't, nor between patients whose LSIL status was confirmed by histology and those with LSIL confirmed by a normal biopsy.

The investigators did find that patients' current HPV status—rather than their baseline status—was important. A negative HPV test at a subsequent visit “shows a good likelihood that LSIL has regressed,” which suggests that HPV testing “could be helpful in monitoring LSIL,” they said.

In addition, the findings suggest that the persistence of multiple HPV types slows rates of regression, but this needs to be examined more closely. More study is also needed to better define appropriate screening strategies, they said.

The findings are similar to those of a smaller study from Brazil, published in 2003 in the Journal of the National Cancer Institute, in which an estimated 92–95% of cases regressed within 24 months, and 5–6 % progressed, according to Anne Szarewski and Peter Sasieni of Cancer Research UK.

“It is becoming increasingly clear that LSIL is a transient manifestation of HPV infection that will only rarely progress to HSIL,” they wrote in an accompanying editorial (Lancet [in press]). “Since there is no point in treating LSIL in young women … we see absolutely no role for colposcopy in adolescents as part of routine management.”

Women who presented to Michigan hospitals with acute ST-segment elevation myocardial infarction waited significantly longer than men to undergo emergency angioplasty—and even men waited too long according to Mauro Moscucci, M.D., of the university.

“We have an ideal target for quality improvement, something we can easily try to correct,” said Dr. Moscucci, who presented the data at the scientific sessions of the American Heart Association and discussed the findings in a later interview. “If we can improve our treatment times, we can substantially reduce the risk of death.”

Dr. Moscucci and his associates analyzed data collected on 1,551 patients who had primary percutaneous coronary intervention for acute ST-segment elevation during a 20-month period ending in June 2004. Patients had the procedure at 1 of the 16 hospitals participating in the regional Blue Cross Blue Shield of Michigan Cardiovascular Consortium.

The investigators found that only 26% of the 442 women who had an emergency angioplasty—and 34% of the 1,069 men—had the procedure within the 90-minute time frame recommended by the American Heart Association and the American College of Cardiology.

On average, women waited more than 118 minutes before treatment began, compared with 106 minutes for men.

Patients of both sexes whose angioplasty began within 90 minutes of arrival at the hospital had a 50% lower risk of dying in the hospital than those who waited longer, said Dr. Moscucci, director of interventional cardiology at the University of Michigan Cardiovascular Center, Ann Arbor.

“Since there's been such a focus on angioplasty recently, we wondered whether the recommended door-to-balloon time of 90 minutes was still significant in terms of survival,” he said. “We found that it's still an important predictor of in-hospital mortality, and that perhaps we're not doing as well as we should.”

Women in the study were more than twice as likely as men to die in the hospital; their mortality rate was about 7%, compared with about 3% in men. When the investigators adjusted for the average older age of women and the higher frequency of comorbidities, they still found higher in-hospital mortality rates for women, Dr. Moscucci said.

The gender-difference findings augment a growing body of research showing that women with heart attacks seek care later, present more often with atypical symptoms and comorbidities such as severe diabetes, and face delays in treatment, he said.

In addition to the greater delays in treatment, the Michigan study showed that it takes longer for women to get to an emergency department in the first place.

Women reported that their symptoms started an average of 105 minutes before they got to the emergency department; the average time for men was 85 minutes.

Dr. Moscucci said that hospital procedures for activating cardiac catheterization labs vary significantly. Labs could be activated faster—which, along with faster diagnosis, would help hasten door-to-balloon times—if more ambulances had the capability to automatically read or transmit ECGs and if more hospitals allowed emergency physicians and not just cardiologists to activate the labs directly, he said.

A recent survey of more than 1,000 women older than 35 years showed that only 47% of women who had head, neck, back, and jaw pain—typical heart attack symptoms—would call their doctor, and just 35% would call 911 or visit an emergency department.

“Women and their families still need a great deal of education. Their symptoms can be very atypical—perhaps only weakness, difficulty breathing, or dizziness,” said Michael J. Bresler, M.D., professor of emergency medicine at Stanford (Calif.) University. Women in whom heart attack is diagnosed “should be rushed to the cath lab or quickly given a lytic drug if immediate catheterization isn't available,” he said.

Women who presented to Michigan hospitals with acute ST-segment elevation myocardial infarction waited significantly longer than men to undergo emergency angioplasty—and even men waited too long according to Mauro Moscucci, M.D., of the university.

“We have an ideal target for quality improvement, something we can easily try to correct,” said Dr. Moscucci, who presented the data at the scientific sessions of the American Heart Association and discussed the findings in a later interview. “If we can improve our treatment times, we can substantially reduce the risk of death.”

Dr. Moscucci and his associates analyzed data collected on 1,551 patients who had primary percutaneous coronary intervention for acute ST-segment elevation during a 20-month period ending in June 2004. Patients had the procedure at 1 of the 16 hospitals participating in the regional Blue Cross Blue Shield of Michigan Cardiovascular Consortium.

The investigators found that only 26% of the 442 women who had an emergency angioplasty—and 34% of the 1,069 men—had the procedure within the 90-minute time frame recommended by the American Heart Association and the American College of Cardiology.

On average, women waited more than 118 minutes before treatment began, compared with 106 minutes for men.

Patients of both sexes whose angioplasty began within 90 minutes of arrival at the hospital had a 50% lower risk of dying in the hospital than those who waited longer, said Dr. Moscucci, director of interventional cardiology at the University of Michigan Cardiovascular Center, Ann Arbor.

“Since there's been such a focus on angioplasty recently, we wondered whether the recommended door-to-balloon time of 90 minutes was still significant in terms of survival,” he said. “We found that it's still an important predictor of in-hospital mortality, and that perhaps we're not doing as well as we should.”

Women in the study were more than twice as likely as men to die in the hospital; their mortality rate was about 7%, compared with about 3% in men. When the investigators adjusted for the average older age of women and the higher frequency of comorbidities, they still found higher in-hospital mortality rates for women, Dr. Moscucci said.

The gender-difference findings augment a growing body of research showing that women with heart attacks seek care later, present more often with atypical symptoms and comorbidities such as severe diabetes, and face delays in treatment, he said.

In addition to the greater delays in treatment, the Michigan study showed that it takes longer for women to get to an emergency department in the first place.

Women reported that their symptoms started an average of 105 minutes before they got to the emergency department; the average time for men was 85 minutes.

Dr. Moscucci said that hospital procedures for activating cardiac catheterization labs vary significantly. Labs could be activated faster—which, along with faster diagnosis, would help hasten door-to-balloon times—if more ambulances had the capability to automatically read or transmit ECGs and if more hospitals allowed emergency physicians and not just cardiologists to activate the labs directly, he said.

A recent survey of more than 1,000 women older than 35 years showed that only 47% of women who had head, neck, back, and jaw pain—typical heart attack symptoms—would call their doctor, and just 35% would call 911 or visit an emergency department.

“Women and their families still need a great deal of education. Their symptoms can be very atypical—perhaps only weakness, difficulty breathing, or dizziness,” said Michael J. Bresler, M.D., professor of emergency medicine at Stanford (Calif.) University. Women in whom heart attack is diagnosed “should be rushed to the cath lab or quickly given a lytic drug if immediate catheterization isn't available,” he said.

Women who presented to Michigan hospitals with acute ST-segment elevation myocardial infarction waited significantly longer than men to undergo emergency angioplasty—and even men waited too long according to Mauro Moscucci, M.D., of the university.

“We have an ideal target for quality improvement, something we can easily try to correct,” said Dr. Moscucci, who presented the data at the scientific sessions of the American Heart Association and discussed the findings in a later interview. “If we can improve our treatment times, we can substantially reduce the risk of death.”

Dr. Moscucci and his associates analyzed data collected on 1,551 patients who had primary percutaneous coronary intervention for acute ST-segment elevation during a 20-month period ending in June 2004. Patients had the procedure at 1 of the 16 hospitals participating in the regional Blue Cross Blue Shield of Michigan Cardiovascular Consortium.

The investigators found that only 26% of the 442 women who had an emergency angioplasty—and 34% of the 1,069 men—had the procedure within the 90-minute time frame recommended by the American Heart Association and the American College of Cardiology.

On average, women waited more than 118 minutes before treatment began, compared with 106 minutes for men.

Patients of both sexes whose angioplasty began within 90 minutes of arrival at the hospital had a 50% lower risk of dying in the hospital than those who waited longer, said Dr. Moscucci, director of interventional cardiology at the University of Michigan Cardiovascular Center, Ann Arbor.

“Since there's been such a focus on angioplasty recently, we wondered whether the recommended door-to-balloon time of 90 minutes was still significant in terms of survival,” he said. “We found that it's still an important predictor of in-hospital mortality, and that perhaps we're not doing as well as we should.”

Women in the study were more than twice as likely as men to die in the hospital; their mortality rate was about 7%, compared with about 3% in men. When the investigators adjusted for the average older age of women and the higher frequency of comorbidities, they still found higher in-hospital mortality rates for women, Dr. Moscucci said.

The gender-difference findings augment a growing body of research showing that women with heart attacks seek care later, present more often with atypical symptoms and comorbidities such as severe diabetes, and face delays in treatment, he said.

In addition to the greater delays in treatment, the Michigan study showed that it takes longer for women to get to an emergency department in the first place.

Women reported that their symptoms started an average of 105 minutes before they got to the emergency department; the average time for men was 85 minutes.

Dr. Moscucci said that hospital procedures for activating cardiac catheterization labs vary significantly. Labs could be activated faster—which, along with faster diagnosis, would help hasten door-to-balloon times—if more ambulances had the capability to automatically read or transmit ECGs and if more hospitals allowed emergency physicians and not just cardiologists to activate the labs directly, he said.

A recent survey of more than 1,000 women older than 35 years showed that only 47% of women who had head, neck, back, and jaw pain—typical heart attack symptoms—would call their doctor, and just 35% would call 911 or visit an emergency department.

“Women and their families still need a great deal of education. Their symptoms can be very atypical—perhaps only weakness, difficulty breathing, or dizziness,” said Michael J. Bresler, M.D., professor of emergency medicine at Stanford (Calif.) University. Women in whom heart attack is diagnosed “should be rushed to the cath lab or quickly given a lytic drug if immediate catheterization isn't available,” he said.

Current guidelines on the use of thrombolytic therapy for acute ischemic stroke are “hopelessly outdated,” Louis R. Caplan, M.D., said in an editorial that accompanied several reports of patient outcomes studies published in the Journal of the American Medical Association.

The guidelines, which are nearly a decade old, exclude from thrombolytic therapy patients who may indeed benefit from it and do not consider the major advances in diagnostic technology that have occurred during the past two decades, said Dr. Caplan, chief of the division of cerebrovascular diseases at Beth Israel Deaconess Medical Center in Boston.

The results of two recent studies on outcomes after thrombolysis are “an important reminder” that few patients with ischemic stroke receive thrombolytic therapy, he said (JAMA 2004;292:1883-5).

On the other hand, this treatment “is not a panacea and may actually cause intracerebral hemorrhage or death” in some patients, said Dr. Caplan, who is also professor of neurology at Harvard Medical School, Boston.

In a study by the German Stroke Registers Study Group on predictors of in-hospital mortality after thrombolysis, only 3% of almost 60,000 patients presenting with acute stroke received intravenous tissue plasminogen activator (tPA). Of the treated patients, 10% died during hospitalization.

In the second study, more than half (51%) of 216 patients treated with alteplase in London, Ont., failed to improve significantly after treatment when the published guidelines were followed.

Neither study reported on causative vascular lesions, or on the extent of infarction before or after treatment—information that can be identified with modern imaging techniques, Dr. Caplan noted.

“If the present guidelines continue to be followed, as in the [two studies], physicians will never know which patients with what degree of infarction and with what vascular lesions and at-risk tissue will benefit from thrombolysis,” he said.

Nor will physicians know “whether intravenous, intraarterial, or combined intravenous and intraarterial [therapies] are best and in what circumstances,” he said. “Clinicians also will not know how alteplase compares with other promising newer thrombolytic agents and, possibly, with other therapies.”

In the German study—a prospective, observational cohort study at 225 community and academic hospitals throughout Germany—researchers reported that the factors predicting in-hospital death after thrombolytic therapy were decreased level of consciousness (an odds ratio of 3.5) and older age (an adjusted odds ratio of 1.6 for each 10-year increment of age).

Each factor independently increased the risk of death, reported Peter U. Heuschmann, M.D., of the University of Münster (Germany), and his associates (JAMA 2004;292:1831-38).

The overall rate of symptomatic intracranial hemorrhage was 7%, and the rate increased with age. One or more serious complications occurred in 27% of all patients in the study, and in 84% of those who died after treatment.

Hospital expertise with use of tPA also was independently associated with the probability of early death after tPA treatment. The risk of in-hospital death decreased by 3% for each additional patient treated with tPA per year, Dr. Heuschmann and his associates reported.

In the Ontario study—a prospective study of acute stroke patients who received alteplase at a university hospital over a 4-year period—investigators reported that a lack of improvement at 24 hours was associated with poor patient outcomes and death at 3 months. At the 3-month follow-up, 20% of the patients had died.

They identified three factors—elevated baseline glucose level (144 mg/dL), cortical involvement, and time to thrombolytic therapy—that predicted a lack of improvement at 24 hours.

For each 5-minute increase in the time that elapsed from symptom onset to treatment, the chance of no improvement increased by 5%, said Gustavo Saposnik, M.D., of the London Health Sciences Centre, and his associates (JAMA 2004;292:1839-44).

Lack of improvement was defined as a difference of 3 points or less between the NIH Stroke Scale score at baseline and at 24 hours.

In his editorial, Dr. Caplan said that although earlier treatment is better, studies have shown that the mandated 3-hour time window for thrombolytic therapy may not be appropriate. “Patients with stroke do not become poor candidates for alteplase when the clock strikes 4 hours,” he said.

In a third study that was reported in the Journal of the American Medical Association, for instance, some patients with basilar artery occlusion improved when alteplase was given intravenously more than 12 hours after symptom onset, Dr. Caplan noted.

On the other hand, some patients have large infarcts in less than 2 hours, “so the risk of thrombolytic treatment may outweigh the benefit,” he said.

Dr. Caplan cautioned against “cookbook guidelines” and said that treatment decisions must utilize modern diagnostic technology and be individually focused on “each given patient with a given lesion and a known extent of infarction.”

There is also an urgent need for more qualified stroke centers, more experienced stroke clinicians, and new ways to get patients to the centers quickly, he said.

Current guidelines on the use of thrombolytic therapy for acute ischemic stroke are “hopelessly outdated,” Louis R. Caplan, M.D., said in an editorial that accompanied several reports of patient outcomes studies published in the Journal of the American Medical Association.

The guidelines, which are nearly a decade old, exclude from thrombolytic therapy patients who may indeed benefit from it and do not consider the major advances in diagnostic technology that have occurred during the past two decades, said Dr. Caplan, chief of the division of cerebrovascular diseases at Beth Israel Deaconess Medical Center in Boston.

The results of two recent studies on outcomes after thrombolysis are “an important reminder” that few patients with ischemic stroke receive thrombolytic therapy, he said (JAMA 2004;292:1883-5).

On the other hand, this treatment “is not a panacea and may actually cause intracerebral hemorrhage or death” in some patients, said Dr. Caplan, who is also professor of neurology at Harvard Medical School, Boston.

In a study by the German Stroke Registers Study Group on predictors of in-hospital mortality after thrombolysis, only 3% of almost 60,000 patients presenting with acute stroke received intravenous tissue plasminogen activator (tPA). Of the treated patients, 10% died during hospitalization.

In the second study, more than half (51%) of 216 patients treated with alteplase in London, Ont., failed to improve significantly after treatment when the published guidelines were followed.

Neither study reported on causative vascular lesions, or on the extent of infarction before or after treatment—information that can be identified with modern imaging techniques, Dr. Caplan noted.

“If the present guidelines continue to be followed, as in the [two studies], physicians will never know which patients with what degree of infarction and with what vascular lesions and at-risk tissue will benefit from thrombolysis,” he said.

Nor will physicians know “whether intravenous, intraarterial, or combined intravenous and intraarterial [therapies] are best and in what circumstances,” he said. “Clinicians also will not know how alteplase compares with other promising newer thrombolytic agents and, possibly, with other therapies.”

In the German study—a prospective, observational cohort study at 225 community and academic hospitals throughout Germany—researchers reported that the factors predicting in-hospital death after thrombolytic therapy were decreased level of consciousness (an odds ratio of 3.5) and older age (an adjusted odds ratio of 1.6 for each 10-year increment of age).

Each factor independently increased the risk of death, reported Peter U. Heuschmann, M.D., of the University of Münster (Germany), and his associates (JAMA 2004;292:1831-38).

The overall rate of symptomatic intracranial hemorrhage was 7%, and the rate increased with age. One or more serious complications occurred in 27% of all patients in the study, and in 84% of those who died after treatment.

Hospital expertise with use of tPA also was independently associated with the probability of early death after tPA treatment. The risk of in-hospital death decreased by 3% for each additional patient treated with tPA per year, Dr. Heuschmann and his associates reported.

In the Ontario study—a prospective study of acute stroke patients who received alteplase at a university hospital over a 4-year period—investigators reported that a lack of improvement at 24 hours was associated with poor patient outcomes and death at 3 months. At the 3-month follow-up, 20% of the patients had died.

They identified three factors—elevated baseline glucose level (144 mg/dL), cortical involvement, and time to thrombolytic therapy—that predicted a lack of improvement at 24 hours.

For each 5-minute increase in the time that elapsed from symptom onset to treatment, the chance of no improvement increased by 5%, said Gustavo Saposnik, M.D., of the London Health Sciences Centre, and his associates (JAMA 2004;292:1839-44).

Lack of improvement was defined as a difference of 3 points or less between the NIH Stroke Scale score at baseline and at 24 hours.

In his editorial, Dr. Caplan said that although earlier treatment is better, studies have shown that the mandated 3-hour time window for thrombolytic therapy may not be appropriate. “Patients with stroke do not become poor candidates for alteplase when the clock strikes 4 hours,” he said.

In a third study that was reported in the Journal of the American Medical Association, for instance, some patients with basilar artery occlusion improved when alteplase was given intravenously more than 12 hours after symptom onset, Dr. Caplan noted.

On the other hand, some patients have large infarcts in less than 2 hours, “so the risk of thrombolytic treatment may outweigh the benefit,” he said.

Dr. Caplan cautioned against “cookbook guidelines” and said that treatment decisions must utilize modern diagnostic technology and be individually focused on “each given patient with a given lesion and a known extent of infarction.”

There is also an urgent need for more qualified stroke centers, more experienced stroke clinicians, and new ways to get patients to the centers quickly, he said.

Current guidelines on the use of thrombolytic therapy for acute ischemic stroke are “hopelessly outdated,” Louis R. Caplan, M.D., said in an editorial that accompanied several reports of patient outcomes studies published in the Journal of the American Medical Association.

The guidelines, which are nearly a decade old, exclude from thrombolytic therapy patients who may indeed benefit from it and do not consider the major advances in diagnostic technology that have occurred during the past two decades, said Dr. Caplan, chief of the division of cerebrovascular diseases at Beth Israel Deaconess Medical Center in Boston.

The results of two recent studies on outcomes after thrombolysis are “an important reminder” that few patients with ischemic stroke receive thrombolytic therapy, he said (JAMA 2004;292:1883-5).

On the other hand, this treatment “is not a panacea and may actually cause intracerebral hemorrhage or death” in some patients, said Dr. Caplan, who is also professor of neurology at Harvard Medical School, Boston.

In a study by the German Stroke Registers Study Group on predictors of in-hospital mortality after thrombolysis, only 3% of almost 60,000 patients presenting with acute stroke received intravenous tissue plasminogen activator (tPA). Of the treated patients, 10% died during hospitalization.

In the second study, more than half (51%) of 216 patients treated with alteplase in London, Ont., failed to improve significantly after treatment when the published guidelines were followed.

Neither study reported on causative vascular lesions, or on the extent of infarction before or after treatment—information that can be identified with modern imaging techniques, Dr. Caplan noted.

“If the present guidelines continue to be followed, as in the [two studies], physicians will never know which patients with what degree of infarction and with what vascular lesions and at-risk tissue will benefit from thrombolysis,” he said.

Nor will physicians know “whether intravenous, intraarterial, or combined intravenous and intraarterial [therapies] are best and in what circumstances,” he said. “Clinicians also will not know how alteplase compares with other promising newer thrombolytic agents and, possibly, with other therapies.”

In the German study—a prospective, observational cohort study at 225 community and academic hospitals throughout Germany—researchers reported that the factors predicting in-hospital death after thrombolytic therapy were decreased level of consciousness (an odds ratio of 3.5) and older age (an adjusted odds ratio of 1.6 for each 10-year increment of age).

Each factor independently increased the risk of death, reported Peter U. Heuschmann, M.D., of the University of Münster (Germany), and his associates (JAMA 2004;292:1831-38).

The overall rate of symptomatic intracranial hemorrhage was 7%, and the rate increased with age. One or more serious complications occurred in 27% of all patients in the study, and in 84% of those who died after treatment.

Hospital expertise with use of tPA also was independently associated with the probability of early death after tPA treatment. The risk of in-hospital death decreased by 3% for each additional patient treated with tPA per year, Dr. Heuschmann and his associates reported.

In the Ontario study—a prospective study of acute stroke patients who received alteplase at a university hospital over a 4-year period—investigators reported that a lack of improvement at 24 hours was associated with poor patient outcomes and death at 3 months. At the 3-month follow-up, 20% of the patients had died.

They identified three factors—elevated baseline glucose level (144 mg/dL), cortical involvement, and time to thrombolytic therapy—that predicted a lack of improvement at 24 hours.

For each 5-minute increase in the time that elapsed from symptom onset to treatment, the chance of no improvement increased by 5%, said Gustavo Saposnik, M.D., of the London Health Sciences Centre, and his associates (JAMA 2004;292:1839-44).

Lack of improvement was defined as a difference of 3 points or less between the NIH Stroke Scale score at baseline and at 24 hours.

In his editorial, Dr. Caplan said that although earlier treatment is better, studies have shown that the mandated 3-hour time window for thrombolytic therapy may not be appropriate. “Patients with stroke do not become poor candidates for alteplase when the clock strikes 4 hours,” he said.

In a third study that was reported in the Journal of the American Medical Association, for instance, some patients with basilar artery occlusion improved when alteplase was given intravenously more than 12 hours after symptom onset, Dr. Caplan noted.

On the other hand, some patients have large infarcts in less than 2 hours, “so the risk of thrombolytic treatment may outweigh the benefit,” he said.

Dr. Caplan cautioned against “cookbook guidelines” and said that treatment decisions must utilize modern diagnostic technology and be individually focused on “each given patient with a given lesion and a known extent of infarction.”

There is also an urgent need for more qualified stroke centers, more experienced stroke clinicians, and new ways to get patients to the centers quickly, he said.

The number of women having primary cesarean sections without any apparent medical risk grew significantly during the 1990s and topped 80,000 in 2001, according to a new analysis of U.S. birth certificate data.

First-time C-sections in women with “no indicated risk” rose 67% between 1991 and 2001, from approximately 3.3% to 5.5%. The increase was gradual until 1996 and rapid toward the end of the study period. Increases were seen across all ages and parities.

Eugene Declercq, Ph.D., and his associates studied birth certificate data on approximately 4 million births per year between 1991 and 2001.

They looked specifically at women who had singleton, full-term, vertex-presentation births, without any medical risk factors or complications of labor or delivery listed on the birth certificate. They then focused on women who had a first-time cesarean.

The investigators declined to call these deliveries “elective” and instead used the term “no indicated risk” cesareans.

“Birth certificate data provide no record of the mother's intent,” said Dr. Declercq, professor in the maternal and child health department at Boston University, and his associates (BMJ [Epub ahead of print] Nov. 19, 2004. Article DOI number: 10.1136/bmj.38279.705336. Available from www.bmj.com

Age was a major factor in the rate of no-indicated-risk cesareans, they said. First-time mothers over 40 were five times more likely to have the procedure than were primiparous mothers aged 20-24.

Of multiparous women over 34 years of age who had previous vaginal births, more than 5% had a no-indicated-risk cesarean in 2001.

No-risk, primary cesareans were performed in a similar proportion—almost 5%- of women under 30 (all parities) in 2001; this represented growth of almost 60% since 1991.

All told, there were 80,028 no-indicated-risk primary C-sections performed in 2001—an increase of more than 25,000 since 1996. This represented approximately 26% of the total increase in primary cesareans between 1996 and 2001.

The number of women having primary cesarean sections without any apparent medical risk grew significantly during the 1990s and topped 80,000 in 2001, according to a new analysis of U.S. birth certificate data.

First-time C-sections in women with “no indicated risk” rose 67% between 1991 and 2001, from approximately 3.3% to 5.5%. The increase was gradual until 1996 and rapid toward the end of the study period. Increases were seen across all ages and parities.

Eugene Declercq, Ph.D., and his associates studied birth certificate data on approximately 4 million births per year between 1991 and 2001.

They looked specifically at women who had singleton, full-term, vertex-presentation births, without any medical risk factors or complications of labor or delivery listed on the birth certificate. They then focused on women who had a first-time cesarean.

The investigators declined to call these deliveries “elective” and instead used the term “no indicated risk” cesareans.

“Birth certificate data provide no record of the mother's intent,” said Dr. Declercq, professor in the maternal and child health department at Boston University, and his associates (BMJ [Epub ahead of print] Nov. 19, 2004. Article DOI number: 10.1136/bmj.38279.705336. Available from www.bmj.com

Age was a major factor in the rate of no-indicated-risk cesareans, they said. First-time mothers over 40 were five times more likely to have the procedure than were primiparous mothers aged 20-24.

Of multiparous women over 34 years of age who had previous vaginal births, more than 5% had a no-indicated-risk cesarean in 2001.

No-risk, primary cesareans were performed in a similar proportion—almost 5%- of women under 30 (all parities) in 2001; this represented growth of almost 60% since 1991.

All told, there were 80,028 no-indicated-risk primary C-sections performed in 2001—an increase of more than 25,000 since 1996. This represented approximately 26% of the total increase in primary cesareans between 1996 and 2001.

The number of women having primary cesarean sections without any apparent medical risk grew significantly during the 1990s and topped 80,000 in 2001, according to a new analysis of U.S. birth certificate data.

First-time C-sections in women with “no indicated risk” rose 67% between 1991 and 2001, from approximately 3.3% to 5.5%. The increase was gradual until 1996 and rapid toward the end of the study period. Increases were seen across all ages and parities.

Eugene Declercq, Ph.D., and his associates studied birth certificate data on approximately 4 million births per year between 1991 and 2001.

They looked specifically at women who had singleton, full-term, vertex-presentation births, without any medical risk factors or complications of labor or delivery listed on the birth certificate. They then focused on women who had a first-time cesarean.

The investigators declined to call these deliveries “elective” and instead used the term “no indicated risk” cesareans.

“Birth certificate data provide no record of the mother's intent,” said Dr. Declercq, professor in the maternal and child health department at Boston University, and his associates (BMJ [Epub ahead of print] Nov. 19, 2004. Article DOI number: 10.1136/bmj.38279.705336. Available from www.bmj.com

Age was a major factor in the rate of no-indicated-risk cesareans, they said. First-time mothers over 40 were five times more likely to have the procedure than were primiparous mothers aged 20-24.

Of multiparous women over 34 years of age who had previous vaginal births, more than 5% had a no-indicated-risk cesarean in 2001.

No-risk, primary cesareans were performed in a similar proportion—almost 5%- of women under 30 (all parities) in 2001; this represented growth of almost 60% since 1991.

All told, there were 80,028 no-indicated-risk primary C-sections performed in 2001—an increase of more than 25,000 since 1996. This represented approximately 26% of the total increase in primary cesareans between 1996 and 2001.