Bruce K. Dixon

SALT LAKE CITY — A national retrospective cohort study suggests that patients with advanced heart failure remain in hospice longer than advanced cancer patients do, and that the Medicare hospice benefit, which is based on a 6-month life expectancy, “is poorly designed for heart failure patients,” according to Kevin T. Bain, Pharm.D.

The study, which was presented at the annual meeting of the American Academy of Hospice and Palliative Medicine and the Hospice and Palliative Nurses Association, included a national cohort of more than 12,000 patients with heart failure. For comparison, the investigators included a second cohort of more than 31,000 cancer patients.

All patients were discharged alive or dead from 500 hospices between Jan. 1, 2004, and June 30, 2005, said Dr. Bain, a research associate with excelleRx in Philadelphia. Researchers at Thomas Jefferson University, Philadelphia, cooperated in the study.

Patients with the larger spectrum of end-stage heart disease (ESHD) are underrepresented in the nation's hospices, Dr. Bain explained, noting that in 2005, 46% of those admitted to hospice had advanced cancer, while only 12% of admissions were for ESHD. “We estimate that patients with heart failure make up about 6% of hospice admissions,” Dr. Bain said in an interview.

Among the study's findings:

▸ The median length of stay was 17 days for HF patients and 14 days for cancer patients. Hospice stays exceeding 6 months were 8% and 1%, respectively.

▸ Heart failure patients were older and more likely to be women.

▸ Heart failure patients were more likely to receive hospice care in the long-term care setting, while cancer patients were more likely to receive care in their own homes.

▸ Fully 20% of HF patients were discharged from hospice alive, compared with 11% of cancer patients.

▸ The mean time to death was 91 and 32 days, while the median time to death was 22 and 16 days for HF and cancer patients, respectively.

The Medicare hospice benefit defines “terminally ill” as a person certified by the attending physician and the hospice medical director to have a life expectancy of 6 months or less.

“This requirement may pose a barrier to patients being referred earlier or more timely to hospice,” Dr. Bain commented in an interview.

“These findings underscore the limitations of the Medicare hospice certification. Heart failure has a difficult prognosis, and we find that patients could be enrolled very late in the disease and may have a short hospice length of stay, or they may be enrolled beyond 6 months,” he said.

The Medicare hospice benefit 'is poorly designed for heart failure patients.' DR. BAIN

SALT LAKE CITY — A national retrospective cohort study suggests that patients with advanced heart failure remain in hospice longer than advanced cancer patients do, and that the Medicare hospice benefit, which is based on a 6-month life expectancy, “is poorly designed for heart failure patients,” according to Kevin T. Bain, Pharm.D.

The study, which was presented at the annual meeting of the American Academy of Hospice and Palliative Medicine and the Hospice and Palliative Nurses Association, included a national cohort of more than 12,000 patients with heart failure. For comparison, the investigators included a second cohort of more than 31,000 cancer patients.

All patients were discharged alive or dead from 500 hospices between Jan. 1, 2004, and June 30, 2005, said Dr. Bain, a research associate with excelleRx in Philadelphia. Researchers at Thomas Jefferson University, Philadelphia, cooperated in the study.

Patients with the larger spectrum of end-stage heart disease (ESHD) are underrepresented in the nation's hospices, Dr. Bain explained, noting that in 2005, 46% of those admitted to hospice had advanced cancer, while only 12% of admissions were for ESHD. “We estimate that patients with heart failure make up about 6% of hospice admissions,” Dr. Bain said in an interview.

Among the study's findings:

▸ The median length of stay was 17 days for HF patients and 14 days for cancer patients. Hospice stays exceeding 6 months were 8% and 1%, respectively.

▸ Heart failure patients were older and more likely to be women.

▸ Heart failure patients were more likely to receive hospice care in the long-term care setting, while cancer patients were more likely to receive care in their own homes.

▸ Fully 20% of HF patients were discharged from hospice alive, compared with 11% of cancer patients.

▸ The mean time to death was 91 and 32 days, while the median time to death was 22 and 16 days for HF and cancer patients, respectively.

The Medicare hospice benefit defines “terminally ill” as a person certified by the attending physician and the hospice medical director to have a life expectancy of 6 months or less.

“This requirement may pose a barrier to patients being referred earlier or more timely to hospice,” Dr. Bain commented in an interview.

“These findings underscore the limitations of the Medicare hospice certification. Heart failure has a difficult prognosis, and we find that patients could be enrolled very late in the disease and may have a short hospice length of stay, or they may be enrolled beyond 6 months,” he said.

The Medicare hospice benefit 'is poorly designed for heart failure patients.' DR. BAIN

SALT LAKE CITY — A national retrospective cohort study suggests that patients with advanced heart failure remain in hospice longer than advanced cancer patients do, and that the Medicare hospice benefit, which is based on a 6-month life expectancy, “is poorly designed for heart failure patients,” according to Kevin T. Bain, Pharm.D.

The study, which was presented at the annual meeting of the American Academy of Hospice and Palliative Medicine and the Hospice and Palliative Nurses Association, included a national cohort of more than 12,000 patients with heart failure. For comparison, the investigators included a second cohort of more than 31,000 cancer patients.

All patients were discharged alive or dead from 500 hospices between Jan. 1, 2004, and June 30, 2005, said Dr. Bain, a research associate with excelleRx in Philadelphia. Researchers at Thomas Jefferson University, Philadelphia, cooperated in the study.

Patients with the larger spectrum of end-stage heart disease (ESHD) are underrepresented in the nation's hospices, Dr. Bain explained, noting that in 2005, 46% of those admitted to hospice had advanced cancer, while only 12% of admissions were for ESHD. “We estimate that patients with heart failure make up about 6% of hospice admissions,” Dr. Bain said in an interview.

Among the study's findings:

▸ The median length of stay was 17 days for HF patients and 14 days for cancer patients. Hospice stays exceeding 6 months were 8% and 1%, respectively.

▸ Heart failure patients were older and more likely to be women.

▸ Heart failure patients were more likely to receive hospice care in the long-term care setting, while cancer patients were more likely to receive care in their own homes.

▸ Fully 20% of HF patients were discharged from hospice alive, compared with 11% of cancer patients.

▸ The mean time to death was 91 and 32 days, while the median time to death was 22 and 16 days for HF and cancer patients, respectively.

The Medicare hospice benefit defines “terminally ill” as a person certified by the attending physician and the hospice medical director to have a life expectancy of 6 months or less.

“This requirement may pose a barrier to patients being referred earlier or more timely to hospice,” Dr. Bain commented in an interview.

“These findings underscore the limitations of the Medicare hospice certification. Heart failure has a difficult prognosis, and we find that patients could be enrolled very late in the disease and may have a short hospice length of stay, or they may be enrolled beyond 6 months,” he said.

The Medicare hospice benefit 'is poorly designed for heart failure patients.' DR. BAIN

ST. LOUIS – In the 1946 movie “It's a Wonderful Life,” a highly stressed George Bailey berates his sick daughter's teacher for sending the tyke home without her overcoat on when, in fact, the teacher was blameless.

Bailey's erroneous assumption serves as an object lesson for therapists dealing with children who have obsessive-compulsive disorder and separation anxiety disorder, clinical psychologist Anna K. Boller, Psy.D., said at the annual conference of the Anxiety Disorders Association of America.

“Therapists too often get sucked into the blame game between parents and teachers because they don't take the time to get both sides of the story,” she said.

“It's one thing to be the child's advocate, and it's quite another to think that you know the whole world view based on what an 8-year-old is telling his parents. So talking to the teacher is critical,” said Dr. Boller, a school counselor at the Waterford School in Sandy, Utah.

Such communication forms the foundation of a collaborative relationship with key adults–including the teacher and parents–in the anxious child's life, said Dr. Boller, who has taught communication courses at the University of Michigan, Ann Arbor, and the University of Illinois at Chicago.

Obsessive-compulsive disorder and separation anxiety disorder are painful for children, and both research-based therapy and a bit of imaginative thinking must be brought to bear, she said.

“Children with anxiety disorders have functional impairment at both home and school, which is a two-edged sword. The good news is, slight changes in the child's environment, such as seating location and placement in line or timing of daily events, can make a tremendous difference,” Dr. Boller said, adding that nothing can be accomplished without forming a collaborative relationship.

“The information you get from talking to the teacher just one time at the beginning of treatment will tell you something you didn't know that's going to be salient to therapy,” she said.

Dr. Boller borrows liberally from two books she urges every therapist to own: “Anxiety Disorders in Children and Adolescents, Second Edition,” edited by Tracy L. Morris and John S. March (New York: Guilford Press, 2004), and “Talking Back to OCD” by John S. March (New York: Guilford Press, 2006).

Dr. Boller conceded that making contact with angry parents who blame the teacher for their child's problems at school can be intimidating. Once all parties have become involved, it is important to avoid the blame game by maintaining focus on observable behaviors without using or trying to interpret value-laden statements, she said.

“The parent may say, 'Joey goes to the restroom frequently to wash his hands because the classroom is such a mess, and everybody's sick because the school makes no effort to maintain hygiene!' Assumptions and blame destroy efforts to help the anxious child,” Dr. Boller said.

In addition, the therapist should seek information before giving information. “Don't call the school and say, 'You have a student in your classroom named Mark who has obsessive-compulsive disorder.' Ask questions first and make it clear to the parents that it's important that you be given clearance to talk to the teacher,” she explained.

After the initial discussion, the therapist and teacher can track the child's progress by exchanging e-mails. The teacher's role in noticing the child's anxiety triggers cannot be underestimated, she said.

“That initial phone call to the teacher and those follow-up e-mails are going to make all the difference for treatment. It's going to lead to relief of suffering at a more effective rate and empower an increasingly self-confident child,” Dr. Boller said.

'Talking to the teacher just one time at the beginning of treatment will tell you something you didn't know.' DR. BOLLER

ST. LOUIS – In the 1946 movie “It's a Wonderful Life,” a highly stressed George Bailey berates his sick daughter's teacher for sending the tyke home without her overcoat on when, in fact, the teacher was blameless.

Bailey's erroneous assumption serves as an object lesson for therapists dealing with children who have obsessive-compulsive disorder and separation anxiety disorder, clinical psychologist Anna K. Boller, Psy.D., said at the annual conference of the Anxiety Disorders Association of America.

“Therapists too often get sucked into the blame game between parents and teachers because they don't take the time to get both sides of the story,” she said.

“It's one thing to be the child's advocate, and it's quite another to think that you know the whole world view based on what an 8-year-old is telling his parents. So talking to the teacher is critical,” said Dr. Boller, a school counselor at the Waterford School in Sandy, Utah.

Such communication forms the foundation of a collaborative relationship with key adults–including the teacher and parents–in the anxious child's life, said Dr. Boller, who has taught communication courses at the University of Michigan, Ann Arbor, and the University of Illinois at Chicago.

Obsessive-compulsive disorder and separation anxiety disorder are painful for children, and both research-based therapy and a bit of imaginative thinking must be brought to bear, she said.

“Children with anxiety disorders have functional impairment at both home and school, which is a two-edged sword. The good news is, slight changes in the child's environment, such as seating location and placement in line or timing of daily events, can make a tremendous difference,” Dr. Boller said, adding that nothing can be accomplished without forming a collaborative relationship.

“The information you get from talking to the teacher just one time at the beginning of treatment will tell you something you didn't know that's going to be salient to therapy,” she said.

Dr. Boller borrows liberally from two books she urges every therapist to own: “Anxiety Disorders in Children and Adolescents, Second Edition,” edited by Tracy L. Morris and John S. March (New York: Guilford Press, 2004), and “Talking Back to OCD” by John S. March (New York: Guilford Press, 2006).

Dr. Boller conceded that making contact with angry parents who blame the teacher for their child's problems at school can be intimidating. Once all parties have become involved, it is important to avoid the blame game by maintaining focus on observable behaviors without using or trying to interpret value-laden statements, she said.

“The parent may say, 'Joey goes to the restroom frequently to wash his hands because the classroom is such a mess, and everybody's sick because the school makes no effort to maintain hygiene!' Assumptions and blame destroy efforts to help the anxious child,” Dr. Boller said.

In addition, the therapist should seek information before giving information. “Don't call the school and say, 'You have a student in your classroom named Mark who has obsessive-compulsive disorder.' Ask questions first and make it clear to the parents that it's important that you be given clearance to talk to the teacher,” she explained.

After the initial discussion, the therapist and teacher can track the child's progress by exchanging e-mails. The teacher's role in noticing the child's anxiety triggers cannot be underestimated, she said.

“That initial phone call to the teacher and those follow-up e-mails are going to make all the difference for treatment. It's going to lead to relief of suffering at a more effective rate and empower an increasingly self-confident child,” Dr. Boller said.

'Talking to the teacher just one time at the beginning of treatment will tell you something you didn't know.' DR. BOLLER

ST. LOUIS – In the 1946 movie “It's a Wonderful Life,” a highly stressed George Bailey berates his sick daughter's teacher for sending the tyke home without her overcoat on when, in fact, the teacher was blameless.

Bailey's erroneous assumption serves as an object lesson for therapists dealing with children who have obsessive-compulsive disorder and separation anxiety disorder, clinical psychologist Anna K. Boller, Psy.D., said at the annual conference of the Anxiety Disorders Association of America.

“Therapists too often get sucked into the blame game between parents and teachers because they don't take the time to get both sides of the story,” she said.

“It's one thing to be the child's advocate, and it's quite another to think that you know the whole world view based on what an 8-year-old is telling his parents. So talking to the teacher is critical,” said Dr. Boller, a school counselor at the Waterford School in Sandy, Utah.

Such communication forms the foundation of a collaborative relationship with key adults–including the teacher and parents–in the anxious child's life, said Dr. Boller, who has taught communication courses at the University of Michigan, Ann Arbor, and the University of Illinois at Chicago.

Obsessive-compulsive disorder and separation anxiety disorder are painful for children, and both research-based therapy and a bit of imaginative thinking must be brought to bear, she said.

“Children with anxiety disorders have functional impairment at both home and school, which is a two-edged sword. The good news is, slight changes in the child's environment, such as seating location and placement in line or timing of daily events, can make a tremendous difference,” Dr. Boller said, adding that nothing can be accomplished without forming a collaborative relationship.

“The information you get from talking to the teacher just one time at the beginning of treatment will tell you something you didn't know that's going to be salient to therapy,” she said.

Dr. Boller borrows liberally from two books she urges every therapist to own: “Anxiety Disorders in Children and Adolescents, Second Edition,” edited by Tracy L. Morris and John S. March (New York: Guilford Press, 2004), and “Talking Back to OCD” by John S. March (New York: Guilford Press, 2006).

Dr. Boller conceded that making contact with angry parents who blame the teacher for their child's problems at school can be intimidating. Once all parties have become involved, it is important to avoid the blame game by maintaining focus on observable behaviors without using or trying to interpret value-laden statements, she said.

“The parent may say, 'Joey goes to the restroom frequently to wash his hands because the classroom is such a mess, and everybody's sick because the school makes no effort to maintain hygiene!' Assumptions and blame destroy efforts to help the anxious child,” Dr. Boller said.

In addition, the therapist should seek information before giving information. “Don't call the school and say, 'You have a student in your classroom named Mark who has obsessive-compulsive disorder.' Ask questions first and make it clear to the parents that it's important that you be given clearance to talk to the teacher,” she explained.

After the initial discussion, the therapist and teacher can track the child's progress by exchanging e-mails. The teacher's role in noticing the child's anxiety triggers cannot be underestimated, she said.

“That initial phone call to the teacher and those follow-up e-mails are going to make all the difference for treatment. It's going to lead to relief of suffering at a more effective rate and empower an increasingly self-confident child,” Dr. Boller said.

'Talking to the teacher just one time at the beginning of treatment will tell you something you didn't know.' DR. BOLLER

Ovarian suppression with luteinizing hormone-releasing hormone agonists is an effective adjuvant treatment for premenopausal women with hormone receptor-positive early breast cancer, according to a meta-analysis of published trials.

“Our results broadly support those of the previous analyses, but also show other important details. Of particular importance is the benefit of LHRH agonists after chemotherapy in women younger than 40 years … and the equivalence of LHRH agonists with chemotherapy” in hormone receptor-positive cancers, wrote Dr. Jack Cuzick of the University of London, and colleagues.

The study of nearly 12,000 premenopausal women randomized in 16 trials showed that luteinizing hormone-releasing hormone (LHRH) agonists were beneficial when used alone, and effective in addition to tamoxifen or chemotherapy, or as an alternative to chemotherapy. Only trials in which more than half the treatments were with an LHRH agonist were included in the analysis (Lancet 2007;369:1711–23).

Hormone-containing drugs used in the studies included goserelin (10,450 patients), triptorelin (821), and leuprorelin (589). Most of the chemotherapy given was cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) based, but anthracycline-based chemotherapy was used for 38% of the patients who received randomized chemotherapy. No patients received taxanes.

The duration of LHRH treatment was 2 years in most trials, but 18-month, 3-year, and 5-year regimens also were used. Treatment duration was 3 years in the two trials using triptorelin.

From the entire cohort of women, the investigators focused on 9,000 hormone receptor-positive patients, who accounted for 76% of all randomized patients. Of these, 92% were estrogen receptor-positive, whereas the remainder were estrogen receptor-negative but progesterone receptor-positive.

The use of an LHRH agonist, compared with no systemic treatment, did not have a significant effect on recurrence, death after recurrence, or death from any cause, but the effect size was large, the authors said, noting that the number of patients included in this comparison was very small.

The use of an LHRH agonist had similar absolute results for rates of recurrence (3.9% increase), death after recurrence (6.7% decrease), and death from any cause (14.9% decrease), compared with chemotherapy.

The addition of LHRH agonists to tamoxifen, chemotherapy, or both reduced the hazard rate for recurrence by 12.7% and for death after recurrence by 15%, the researchers said, adding that LHRH agonists showed similar efficacy to chemotherapy.

LHRH agonists were ineffective in hormone receptor-negative tumors.

“The scope, focus, and rigor of this overview lend substantial weight to its findings,” Dr. Nicholas Wilcken and Dr. Martin Stockler wrote in an accompanying editorial. They pointed out that a previous meta-analysis on the subject was reported in 2005, with data obtained in 2000, lending this newer and larger study additional weight (Lancet 2007;369:1668–70).

This meta-analysis “has established that ovarian suppression is an active treatment” in the setting of hormone receptor-positive breast cancer in premenopausal women, and “one that can be regarded as a reasonable alternative to chemotherapy in women with low-risk disease,” said Dr. Wilcken and Dr. Stockler of the University of Sydney. “In women with higher-risk disease, chemotherapy followed by tamoxifen should still be the standard approach, with the addition of an LHRH analogue a reasonable consideration for those who remain premenopausal.”

They added that it is not yet known whether ovarian suppression is as effective as chemotherapy when tamoxifen is used.

Another important question is whether adding an LHRH agonist is only useful when amenorrhea is not achieved with chemotherapy, said Dr. Cuzick and colleagues. “Some trials have shown a worse outcome after chemotherapy in women who did not experience amenorrhea after chemotherapy, and these women could be the ones who benefit most from the addition of an LHRH agonist,” they said.

Ovarian suppression with luteinizing hormone-releasing hormone agonists is an effective adjuvant treatment for premenopausal women with hormone receptor-positive early breast cancer, according to a meta-analysis of published trials.

“Our results broadly support those of the previous analyses, but also show other important details. Of particular importance is the benefit of LHRH agonists after chemotherapy in women younger than 40 years … and the equivalence of LHRH agonists with chemotherapy” in hormone receptor-positive cancers, wrote Dr. Jack Cuzick of the University of London, and colleagues.

The study of nearly 12,000 premenopausal women randomized in 16 trials showed that luteinizing hormone-releasing hormone (LHRH) agonists were beneficial when used alone, and effective in addition to tamoxifen or chemotherapy, or as an alternative to chemotherapy. Only trials in which more than half the treatments were with an LHRH agonist were included in the analysis (Lancet 2007;369:1711–23).

Hormone-containing drugs used in the studies included goserelin (10,450 patients), triptorelin (821), and leuprorelin (589). Most of the chemotherapy given was cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) based, but anthracycline-based chemotherapy was used for 38% of the patients who received randomized chemotherapy. No patients received taxanes.

The duration of LHRH treatment was 2 years in most trials, but 18-month, 3-year, and 5-year regimens also were used. Treatment duration was 3 years in the two trials using triptorelin.

From the entire cohort of women, the investigators focused on 9,000 hormone receptor-positive patients, who accounted for 76% of all randomized patients. Of these, 92% were estrogen receptor-positive, whereas the remainder were estrogen receptor-negative but progesterone receptor-positive.

The use of an LHRH agonist, compared with no systemic treatment, did not have a significant effect on recurrence, death after recurrence, or death from any cause, but the effect size was large, the authors said, noting that the number of patients included in this comparison was very small.

The use of an LHRH agonist had similar absolute results for rates of recurrence (3.9% increase), death after recurrence (6.7% decrease), and death from any cause (14.9% decrease), compared with chemotherapy.

The addition of LHRH agonists to tamoxifen, chemotherapy, or both reduced the hazard rate for recurrence by 12.7% and for death after recurrence by 15%, the researchers said, adding that LHRH agonists showed similar efficacy to chemotherapy.

LHRH agonists were ineffective in hormone receptor-negative tumors.

“The scope, focus, and rigor of this overview lend substantial weight to its findings,” Dr. Nicholas Wilcken and Dr. Martin Stockler wrote in an accompanying editorial. They pointed out that a previous meta-analysis on the subject was reported in 2005, with data obtained in 2000, lending this newer and larger study additional weight (Lancet 2007;369:1668–70).

This meta-analysis “has established that ovarian suppression is an active treatment” in the setting of hormone receptor-positive breast cancer in premenopausal women, and “one that can be regarded as a reasonable alternative to chemotherapy in women with low-risk disease,” said Dr. Wilcken and Dr. Stockler of the University of Sydney. “In women with higher-risk disease, chemotherapy followed by tamoxifen should still be the standard approach, with the addition of an LHRH analogue a reasonable consideration for those who remain premenopausal.”

They added that it is not yet known whether ovarian suppression is as effective as chemotherapy when tamoxifen is used.

Another important question is whether adding an LHRH agonist is only useful when amenorrhea is not achieved with chemotherapy, said Dr. Cuzick and colleagues. “Some trials have shown a worse outcome after chemotherapy in women who did not experience amenorrhea after chemotherapy, and these women could be the ones who benefit most from the addition of an LHRH agonist,” they said.

Ovarian suppression with luteinizing hormone-releasing hormone agonists is an effective adjuvant treatment for premenopausal women with hormone receptor-positive early breast cancer, according to a meta-analysis of published trials.

“Our results broadly support those of the previous analyses, but also show other important details. Of particular importance is the benefit of LHRH agonists after chemotherapy in women younger than 40 years … and the equivalence of LHRH agonists with chemotherapy” in hormone receptor-positive cancers, wrote Dr. Jack Cuzick of the University of London, and colleagues.

The study of nearly 12,000 premenopausal women randomized in 16 trials showed that luteinizing hormone-releasing hormone (LHRH) agonists were beneficial when used alone, and effective in addition to tamoxifen or chemotherapy, or as an alternative to chemotherapy. Only trials in which more than half the treatments were with an LHRH agonist were included in the analysis (Lancet 2007;369:1711–23).

Hormone-containing drugs used in the studies included goserelin (10,450 patients), triptorelin (821), and leuprorelin (589). Most of the chemotherapy given was cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) based, but anthracycline-based chemotherapy was used for 38% of the patients who received randomized chemotherapy. No patients received taxanes.

The duration of LHRH treatment was 2 years in most trials, but 18-month, 3-year, and 5-year regimens also were used. Treatment duration was 3 years in the two trials using triptorelin.

From the entire cohort of women, the investigators focused on 9,000 hormone receptor-positive patients, who accounted for 76% of all randomized patients. Of these, 92% were estrogen receptor-positive, whereas the remainder were estrogen receptor-negative but progesterone receptor-positive.

The use of an LHRH agonist, compared with no systemic treatment, did not have a significant effect on recurrence, death after recurrence, or death from any cause, but the effect size was large, the authors said, noting that the number of patients included in this comparison was very small.

The use of an LHRH agonist had similar absolute results for rates of recurrence (3.9% increase), death after recurrence (6.7% decrease), and death from any cause (14.9% decrease), compared with chemotherapy.

The addition of LHRH agonists to tamoxifen, chemotherapy, or both reduced the hazard rate for recurrence by 12.7% and for death after recurrence by 15%, the researchers said, adding that LHRH agonists showed similar efficacy to chemotherapy.

LHRH agonists were ineffective in hormone receptor-negative tumors.

“The scope, focus, and rigor of this overview lend substantial weight to its findings,” Dr. Nicholas Wilcken and Dr. Martin Stockler wrote in an accompanying editorial. They pointed out that a previous meta-analysis on the subject was reported in 2005, with data obtained in 2000, lending this newer and larger study additional weight (Lancet 2007;369:1668–70).

This meta-analysis “has established that ovarian suppression is an active treatment” in the setting of hormone receptor-positive breast cancer in premenopausal women, and “one that can be regarded as a reasonable alternative to chemotherapy in women with low-risk disease,” said Dr. Wilcken and Dr. Stockler of the University of Sydney. “In women with higher-risk disease, chemotherapy followed by tamoxifen should still be the standard approach, with the addition of an LHRH analogue a reasonable consideration for those who remain premenopausal.”

They added that it is not yet known whether ovarian suppression is as effective as chemotherapy when tamoxifen is used.

Another important question is whether adding an LHRH agonist is only useful when amenorrhea is not achieved with chemotherapy, said Dr. Cuzick and colleagues. “Some trials have shown a worse outcome after chemotherapy in women who did not experience amenorrhea after chemotherapy, and these women could be the ones who benefit most from the addition of an LHRH agonist,” they said.

CHICAGO – The high-profile corporate scandals of the past decade have brought renewed interest in destructive and dysfunctional leadership and how it can be identified and mitigated, Dr. Vineeth P. John said at the annual conference of the Academy of Organizational and Occupational Psychiatry.

Occupational psychiatrists and psychologists should be familiar with the concept of toxic leadership so that they can confront the issue and help the business world understand the paradigms and psychodynamic underpinnings of corporate narcissism, Dr. John said in an interview.

“We have to create and employ appropriate measures to counter the impact of toxic leadership and create awareness of the enormous cost to society of this sort of behavior,” said Dr. John of the psychiatry department at the University of Wisconsin, Madison. He noted that the term “toxic leader,” frequently heard in the debate about corporate ethics and the issue of accounting scandals, was coined in 2004 by Jean Lipman-Blumen in her book “The Allure of Toxic Leaders: Why We Follow Destructive Bosses and Corrupt Politicians–and How We Can Survive Them” (N.Y.: Oxford University Press, 2006).

According to Ms. Lipman-Blumen, any one of several qualities can help to identify a toxic leader, including lack of integrity, insatiable ambition, enormous ego, arrogance, avarice, amorality, cowardice, and incompetence. Toxic leaders tend to violate basic human rights, feed followers' “illusions,” stifle criticism, and identify scapegoats, Dr. John said.

Barbara Kellerman, in her book “Bad Leadership: What It Is, How It Happens, Why It Matters” (Cambridge: Harvard Business School Press, 2004), identified seven kinds of bad leadership: incompetent, rigid, intemperate, callous, corrupt, insular, and evil. Such leaders often are tolerated because they provide jobs and income, Dr. John explained at the conference, which was cosponsored by the American College of Occupational and Environmental Medicine.

The keystone in the arch of toxic leadership is narcissism. A desire for power, and the need to win at all costs might indicate the presence of narcissistic personality disorder. Dr. John noted that the more those around toxic leaders try to understand their motives, the more vulnerable these followers become. The toxic leader, his constituency, and the organizational culture within which they work create what Dr. John calls a “toxic triad” that promotes mediocrity over merit, management by intimidation, and age and gender silos. In these situations, prominence often is given to the leader's personal agendas above sound organizational strategy.

In addition, the toxic work culture is characterized by several other factors, including:

▸ Vague job descriptions.

▸ Constant flux in the organizational climate and poor coordination among divisions.

▸ Hostile style of conducting meetings.

▸ Tolerance of abusive behavior by senior management.

The real costs of toxic leadership include stress, burnout, posttraumatic stress disorder, loss of share value, loss of jobs and pensions, bankruptcy, destruction of the organization, and perhaps even destruction of communities, cities, and nations, Dr. John said.

On the other hand, a countermovement called “productive narcissism” is expounded by Michael Maccoby in his book “The Productive Narcissist: The Promise and Peril of Visionary Leadership” (N.Y.: Random House, 2003). Mr. Maccoby posits that narcissism can be useful to a company in crisis that could benefit from a leader whose strategic intelligence can take the organization to the next level, Dr. John said. Winston Churchill has been described as a “productive narcissist” who stepped forward to lead a country in crisis to victory.

CHICAGO – The high-profile corporate scandals of the past decade have brought renewed interest in destructive and dysfunctional leadership and how it can be identified and mitigated, Dr. Vineeth P. John said at the annual conference of the Academy of Organizational and Occupational Psychiatry.

Occupational psychiatrists and psychologists should be familiar with the concept of toxic leadership so that they can confront the issue and help the business world understand the paradigms and psychodynamic underpinnings of corporate narcissism, Dr. John said in an interview.

“We have to create and employ appropriate measures to counter the impact of toxic leadership and create awareness of the enormous cost to society of this sort of behavior,” said Dr. John of the psychiatry department at the University of Wisconsin, Madison. He noted that the term “toxic leader,” frequently heard in the debate about corporate ethics and the issue of accounting scandals, was coined in 2004 by Jean Lipman-Blumen in her book “The Allure of Toxic Leaders: Why We Follow Destructive Bosses and Corrupt Politicians–and How We Can Survive Them” (N.Y.: Oxford University Press, 2006).

According to Ms. Lipman-Blumen, any one of several qualities can help to identify a toxic leader, including lack of integrity, insatiable ambition, enormous ego, arrogance, avarice, amorality, cowardice, and incompetence. Toxic leaders tend to violate basic human rights, feed followers' “illusions,” stifle criticism, and identify scapegoats, Dr. John said.

Barbara Kellerman, in her book “Bad Leadership: What It Is, How It Happens, Why It Matters” (Cambridge: Harvard Business School Press, 2004), identified seven kinds of bad leadership: incompetent, rigid, intemperate, callous, corrupt, insular, and evil. Such leaders often are tolerated because they provide jobs and income, Dr. John explained at the conference, which was cosponsored by the American College of Occupational and Environmental Medicine.

The keystone in the arch of toxic leadership is narcissism. A desire for power, and the need to win at all costs might indicate the presence of narcissistic personality disorder. Dr. John noted that the more those around toxic leaders try to understand their motives, the more vulnerable these followers become. The toxic leader, his constituency, and the organizational culture within which they work create what Dr. John calls a “toxic triad” that promotes mediocrity over merit, management by intimidation, and age and gender silos. In these situations, prominence often is given to the leader's personal agendas above sound organizational strategy.

In addition, the toxic work culture is characterized by several other factors, including:

▸ Vague job descriptions.

▸ Constant flux in the organizational climate and poor coordination among divisions.

▸ Hostile style of conducting meetings.

▸ Tolerance of abusive behavior by senior management.

The real costs of toxic leadership include stress, burnout, posttraumatic stress disorder, loss of share value, loss of jobs and pensions, bankruptcy, destruction of the organization, and perhaps even destruction of communities, cities, and nations, Dr. John said.

On the other hand, a countermovement called “productive narcissism” is expounded by Michael Maccoby in his book “The Productive Narcissist: The Promise and Peril of Visionary Leadership” (N.Y.: Random House, 2003). Mr. Maccoby posits that narcissism can be useful to a company in crisis that could benefit from a leader whose strategic intelligence can take the organization to the next level, Dr. John said. Winston Churchill has been described as a “productive narcissist” who stepped forward to lead a country in crisis to victory.

CHICAGO – The high-profile corporate scandals of the past decade have brought renewed interest in destructive and dysfunctional leadership and how it can be identified and mitigated, Dr. Vineeth P. John said at the annual conference of the Academy of Organizational and Occupational Psychiatry.

Occupational psychiatrists and psychologists should be familiar with the concept of toxic leadership so that they can confront the issue and help the business world understand the paradigms and psychodynamic underpinnings of corporate narcissism, Dr. John said in an interview.

“We have to create and employ appropriate measures to counter the impact of toxic leadership and create awareness of the enormous cost to society of this sort of behavior,” said Dr. John of the psychiatry department at the University of Wisconsin, Madison. He noted that the term “toxic leader,” frequently heard in the debate about corporate ethics and the issue of accounting scandals, was coined in 2004 by Jean Lipman-Blumen in her book “The Allure of Toxic Leaders: Why We Follow Destructive Bosses and Corrupt Politicians–and How We Can Survive Them” (N.Y.: Oxford University Press, 2006).

According to Ms. Lipman-Blumen, any one of several qualities can help to identify a toxic leader, including lack of integrity, insatiable ambition, enormous ego, arrogance, avarice, amorality, cowardice, and incompetence. Toxic leaders tend to violate basic human rights, feed followers' “illusions,” stifle criticism, and identify scapegoats, Dr. John said.

Barbara Kellerman, in her book “Bad Leadership: What It Is, How It Happens, Why It Matters” (Cambridge: Harvard Business School Press, 2004), identified seven kinds of bad leadership: incompetent, rigid, intemperate, callous, corrupt, insular, and evil. Such leaders often are tolerated because they provide jobs and income, Dr. John explained at the conference, which was cosponsored by the American College of Occupational and Environmental Medicine.

The keystone in the arch of toxic leadership is narcissism. A desire for power, and the need to win at all costs might indicate the presence of narcissistic personality disorder. Dr. John noted that the more those around toxic leaders try to understand their motives, the more vulnerable these followers become. The toxic leader, his constituency, and the organizational culture within which they work create what Dr. John calls a “toxic triad” that promotes mediocrity over merit, management by intimidation, and age and gender silos. In these situations, prominence often is given to the leader's personal agendas above sound organizational strategy.

In addition, the toxic work culture is characterized by several other factors, including:

▸ Vague job descriptions.

▸ Constant flux in the organizational climate and poor coordination among divisions.

▸ Hostile style of conducting meetings.

▸ Tolerance of abusive behavior by senior management.

The real costs of toxic leadership include stress, burnout, posttraumatic stress disorder, loss of share value, loss of jobs and pensions, bankruptcy, destruction of the organization, and perhaps even destruction of communities, cities, and nations, Dr. John said.

On the other hand, a countermovement called “productive narcissism” is expounded by Michael Maccoby in his book “The Productive Narcissist: The Promise and Peril of Visionary Leadership” (N.Y.: Random House, 2003). Mr. Maccoby posits that narcissism can be useful to a company in crisis that could benefit from a leader whose strategic intelligence can take the organization to the next level, Dr. John said. Winston Churchill has been described as a “productive narcissist” who stepped forward to lead a country in crisis to victory.

CHICAGO – American physicians and their patients face a common enemy: work-related stress and burnout resulting from a conflict between work and everything else that's important, including family, friends, personal health, and spouses, Lt. Col. Steven E. Pflanz, MC, USAF, said at the annual conference of the Academy of Organizational and Occupational Psychiatry.

“Not only do we need to be conscious of work-life balance for ourselves as psychiatrists, but I think we also need to attend to this in therapy sessions with patients whose health is threatened by work stress,” said Dr. Pflanz, chief of the Air Force Suicide Prevention Program.

It is estimated that the average American works a 47-hour week year-round, which represents an 8% increase in a generation. The result is less time for home, family, and recreational activities, said Dr. Pflanz, who also works as a senior psychiatry policy analyst at the Air Force Medical Operations Agency in Falls Church, Va.

Stress occurs when requirements of the job do not match the capabilities, resources, or needs of the worker, and when the role demands of work conflict directly with the role demands of other life domains, he said. “I would argue that the way you change this is by changing the requirements of the job; changing the job itself; or by changing the capabilities, resources, and the needs of the worker,” he said. “If the job carries unrealistic expectations, you ratchet back on those expectations.”

In the case of overworked primary care physicians, a solution might be to reduce the patient load, he added.

Surveys suggest that one-fourth of employees view their jobs as their leading life stressor, three-fourths of employees believe work is more stressful than it was a generation ago, one-half report working 12-hour days and/or skipping lunch because of the stress of job demands, and 12% had called in sick because of job stress.

In a 2006 ComPsych Corp. survey, more than half of workers had “high levels of stress with extreme fatigue and feeling out of control.” The top three work stressors in that survey were people issues, workload, and work-life balance, Dr. Pflanz said. Symptoms of work stress and burnout that physicians should be aware of include anxiety, depression, irritability, fatigue, cynicism, sleep disturbance, poor concentration, impaired performance, absenteeism, job dissatisfaction, low morale, and dread of going to work.

He provided his own definition of job burnout: “Being overwhelmed by work makes a person decreasingly effective at meeting a variety of life role obligations and responsibilities, and the walls are crumbling all around him or her.”

One of the most powerful risk factors for burnout is an organizational culture that reinforces saying yes and discourages actively or passively saying no, he added.

“This happens in both medicine and in the military, where I work. Everyone wants to be the 'go-to' person,” he said. “You want to get into medical school and achieve a successful residency, so you always say yes. In the military you want to get promoted, so you always say yes.”

A second important risk factor is lack of autonomy: Stressed-out workers tend to be less involved in decision making and tend to have little control over their own jobs. “Autonomy is especially important to physicians, who need to feel that they are controlling their practices, the hours they work, and the treatments they provide,” Dr. Pflanz said. Physicians are prone to work stress because they have high expectations of themselves and others, are not good at setting limits for themselves, and are strongly reinforced to put service before self.

When physicians don't perform up to their own expectations, they feel guilt. Also, the burned-out psychiatrist is much more likely to overidentify with his burned-out patient, which can lead to loss of objectivity and professional judgment, he said at the meeting, cosponsored by the American College of Occupational and Environmental Medicine.

“You can begin to feel ineffective or incompetent and nihilistic toward a patient's care, which may lead to less aggressive therapy and less attention to the treatment options,” he pointed out.

It may even get to the point where burnout causes the doctor to believe that his patient is not ever going to get better.

Workplace support is a critical mediator of work stress and burnout. “If you have a really tight unit or group, you can tolerate a lot more adversity than if you're working in a dysfunctional environment” he added.

In addition, American culture tends to overvalue the work ethic and its financial rewards at the expense of nonwork activities and concerns. Eventually, being overwhelmed by role demands or role conflict will wear you down, Dr. Pflanz said.

“Lower your standards if necessary, and recognize when close enough is good enough, because not every problem can be solved,” he said.

Psychiatrists should address these issues in therapy sessions with patients under work stress. DR. PFLANZ

CHICAGO – American physicians and their patients face a common enemy: work-related stress and burnout resulting from a conflict between work and everything else that's important, including family, friends, personal health, and spouses, Lt. Col. Steven E. Pflanz, MC, USAF, said at the annual conference of the Academy of Organizational and Occupational Psychiatry.

“Not only do we need to be conscious of work-life balance for ourselves as psychiatrists, but I think we also need to attend to this in therapy sessions with patients whose health is threatened by work stress,” said Dr. Pflanz, chief of the Air Force Suicide Prevention Program.

It is estimated that the average American works a 47-hour week year-round, which represents an 8% increase in a generation. The result is less time for home, family, and recreational activities, said Dr. Pflanz, who also works as a senior psychiatry policy analyst at the Air Force Medical Operations Agency in Falls Church, Va.

Stress occurs when requirements of the job do not match the capabilities, resources, or needs of the worker, and when the role demands of work conflict directly with the role demands of other life domains, he said. “I would argue that the way you change this is by changing the requirements of the job; changing the job itself; or by changing the capabilities, resources, and the needs of the worker,” he said. “If the job carries unrealistic expectations, you ratchet back on those expectations.”

In the case of overworked primary care physicians, a solution might be to reduce the patient load, he added.

Surveys suggest that one-fourth of employees view their jobs as their leading life stressor, three-fourths of employees believe work is more stressful than it was a generation ago, one-half report working 12-hour days and/or skipping lunch because of the stress of job demands, and 12% had called in sick because of job stress.

In a 2006 ComPsych Corp. survey, more than half of workers had “high levels of stress with extreme fatigue and feeling out of control.” The top three work stressors in that survey were people issues, workload, and work-life balance, Dr. Pflanz said. Symptoms of work stress and burnout that physicians should be aware of include anxiety, depression, irritability, fatigue, cynicism, sleep disturbance, poor concentration, impaired performance, absenteeism, job dissatisfaction, low morale, and dread of going to work.

He provided his own definition of job burnout: “Being overwhelmed by work makes a person decreasingly effective at meeting a variety of life role obligations and responsibilities, and the walls are crumbling all around him or her.”

One of the most powerful risk factors for burnout is an organizational culture that reinforces saying yes and discourages actively or passively saying no, he added.

“This happens in both medicine and in the military, where I work. Everyone wants to be the 'go-to' person,” he said. “You want to get into medical school and achieve a successful residency, so you always say yes. In the military you want to get promoted, so you always say yes.”

A second important risk factor is lack of autonomy: Stressed-out workers tend to be less involved in decision making and tend to have little control over their own jobs. “Autonomy is especially important to physicians, who need to feel that they are controlling their practices, the hours they work, and the treatments they provide,” Dr. Pflanz said. Physicians are prone to work stress because they have high expectations of themselves and others, are not good at setting limits for themselves, and are strongly reinforced to put service before self.

When physicians don't perform up to their own expectations, they feel guilt. Also, the burned-out psychiatrist is much more likely to overidentify with his burned-out patient, which can lead to loss of objectivity and professional judgment, he said at the meeting, cosponsored by the American College of Occupational and Environmental Medicine.

“You can begin to feel ineffective or incompetent and nihilistic toward a patient's care, which may lead to less aggressive therapy and less attention to the treatment options,” he pointed out.

It may even get to the point where burnout causes the doctor to believe that his patient is not ever going to get better.

Workplace support is a critical mediator of work stress and burnout. “If you have a really tight unit or group, you can tolerate a lot more adversity than if you're working in a dysfunctional environment” he added.

In addition, American culture tends to overvalue the work ethic and its financial rewards at the expense of nonwork activities and concerns. Eventually, being overwhelmed by role demands or role conflict will wear you down, Dr. Pflanz said.

“Lower your standards if necessary, and recognize when close enough is good enough, because not every problem can be solved,” he said.

Psychiatrists should address these issues in therapy sessions with patients under work stress. DR. PFLANZ

CHICAGO – American physicians and their patients face a common enemy: work-related stress and burnout resulting from a conflict between work and everything else that's important, including family, friends, personal health, and spouses, Lt. Col. Steven E. Pflanz, MC, USAF, said at the annual conference of the Academy of Organizational and Occupational Psychiatry.

“Not only do we need to be conscious of work-life balance for ourselves as psychiatrists, but I think we also need to attend to this in therapy sessions with patients whose health is threatened by work stress,” said Dr. Pflanz, chief of the Air Force Suicide Prevention Program.

It is estimated that the average American works a 47-hour week year-round, which represents an 8% increase in a generation. The result is less time for home, family, and recreational activities, said Dr. Pflanz, who also works as a senior psychiatry policy analyst at the Air Force Medical Operations Agency in Falls Church, Va.

Stress occurs when requirements of the job do not match the capabilities, resources, or needs of the worker, and when the role demands of work conflict directly with the role demands of other life domains, he said. “I would argue that the way you change this is by changing the requirements of the job; changing the job itself; or by changing the capabilities, resources, and the needs of the worker,” he said. “If the job carries unrealistic expectations, you ratchet back on those expectations.”

In the case of overworked primary care physicians, a solution might be to reduce the patient load, he added.

Surveys suggest that one-fourth of employees view their jobs as their leading life stressor, three-fourths of employees believe work is more stressful than it was a generation ago, one-half report working 12-hour days and/or skipping lunch because of the stress of job demands, and 12% had called in sick because of job stress.

In a 2006 ComPsych Corp. survey, more than half of workers had “high levels of stress with extreme fatigue and feeling out of control.” The top three work stressors in that survey were people issues, workload, and work-life balance, Dr. Pflanz said. Symptoms of work stress and burnout that physicians should be aware of include anxiety, depression, irritability, fatigue, cynicism, sleep disturbance, poor concentration, impaired performance, absenteeism, job dissatisfaction, low morale, and dread of going to work.

He provided his own definition of job burnout: “Being overwhelmed by work makes a person decreasingly effective at meeting a variety of life role obligations and responsibilities, and the walls are crumbling all around him or her.”

One of the most powerful risk factors for burnout is an organizational culture that reinforces saying yes and discourages actively or passively saying no, he added.

“This happens in both medicine and in the military, where I work. Everyone wants to be the 'go-to' person,” he said. “You want to get into medical school and achieve a successful residency, so you always say yes. In the military you want to get promoted, so you always say yes.”

A second important risk factor is lack of autonomy: Stressed-out workers tend to be less involved in decision making and tend to have little control over their own jobs. “Autonomy is especially important to physicians, who need to feel that they are controlling their practices, the hours they work, and the treatments they provide,” Dr. Pflanz said. Physicians are prone to work stress because they have high expectations of themselves and others, are not good at setting limits for themselves, and are strongly reinforced to put service before self.

When physicians don't perform up to their own expectations, they feel guilt. Also, the burned-out psychiatrist is much more likely to overidentify with his burned-out patient, which can lead to loss of objectivity and professional judgment, he said at the meeting, cosponsored by the American College of Occupational and Environmental Medicine.

“You can begin to feel ineffective or incompetent and nihilistic toward a patient's care, which may lead to less aggressive therapy and less attention to the treatment options,” he pointed out.

It may even get to the point where burnout causes the doctor to believe that his patient is not ever going to get better.

Workplace support is a critical mediator of work stress and burnout. “If you have a really tight unit or group, you can tolerate a lot more adversity than if you're working in a dysfunctional environment” he added.

In addition, American culture tends to overvalue the work ethic and its financial rewards at the expense of nonwork activities and concerns. Eventually, being overwhelmed by role demands or role conflict will wear you down, Dr. Pflanz said.

“Lower your standards if necessary, and recognize when close enough is good enough, because not every problem can be solved,” he said.

Psychiatrists should address these issues in therapy sessions with patients under work stress. DR. PFLANZ

CHICAGO – An enzyme found in brain cells may become the first bedside biomarker for assessing the severity of traumatic brain injury, according to Dr. Linda Papa.

In a multicenter trial, levels of the enzyme ubiquitin C-terminal hydrolase (UCH-L1) rose significantly in severely injured brains, an increase that paralleled the rise in cerebral spinal fluid and correlated with the Glasgow Coma Scale (GCS) score, Dr. Papa said at the annual meeting of the Society for Academic Emergency Medicine.

“We know that biomarkers can provide diagnostic and prognostic information, give us insight into the pathophysiology of the brain injury, and guide therapy in both the emergency department and intensive care unit,” said Dr. Papa, director of academic clinical research at Orlando (Fla.) Regional Medical Center.

If further study confirms the value of UCH-L1 as the first clinical biomarker in traumatic brain injury (TBI), physicians will be better able to identify targets for drug therapy and guide the timing of treatment with such agents as tissue plasminogen activator, she explained.

This prospective case-control study enrolled consecutive adult patients presenting to two tertiary care teaching hospitals following severe TBIs, defined by a GCS score of less than 8 and requiring invasive intracerebral monitoring.

The primary outcome was severity of injury as measured by postresuscitation and 24-hour dichotomized GCS score. Secondary outcome included the presence of evolving lesions on CT scan at 24 and 72 hours post injury. Over 16 months, 41 patients with severe TBI were enrolled. Their mean age was 38 years, and four-fifths were men. Patients were excluded if they did not have ventriculostomy, which is necessary to obtain cerebrospinal fluid (CSF).

Ventricular CSF was drained from each patient at 6, 12, 24, 48, 72, and 96 hours after TBI and was measured by enzyme-linked immunosorbent assay for UCH-L1 levels.

The control group consisted of uninjured patients who required CSF drainage for other reasons. Mean 12-hour UCH-L1 levels were 145 ng/mL for patients with GCS scores of 3–5, and 38.5 ng/mL in those with GCS scores of 6–8. Similarly, 24-hour levels were 76 and 36 ng/mL for those with GCS scores of 3–5 and 6–8, respectively.

The largest increase in the experimental biomarker occurred during the first 48 hours after injury. “Then we found that patients with evolving lesions had significantly higher levels of the biomarker” than did patients with nonevolving lesions at both 48 and 72 hours, she said.

“There is a significant increase in CSF UCH-L1 following severe human TBI compared to uninjured controls, and there is a significant association with severity of injury as measured by GCS and the presence of evolving lesions on CT,” Dr. Papa said, adding that these data suggest that UCH-L1 is a potential TBI biomarker. Dr. Papa said more than 5 million Americans live with TBI disabilities, and the hospital and fatality costs related to TBI exceed $48 billion annually.

'Patients with evolving lesions had significantly higher levels of the biomarker' after 48 hours. DR. PAPA

CHICAGO – An enzyme found in brain cells may become the first bedside biomarker for assessing the severity of traumatic brain injury, according to Dr. Linda Papa.

In a multicenter trial, levels of the enzyme ubiquitin C-terminal hydrolase (UCH-L1) rose significantly in severely injured brains, an increase that paralleled the rise in cerebral spinal fluid and correlated with the Glasgow Coma Scale (GCS) score, Dr. Papa said at the annual meeting of the Society for Academic Emergency Medicine.

“We know that biomarkers can provide diagnostic and prognostic information, give us insight into the pathophysiology of the brain injury, and guide therapy in both the emergency department and intensive care unit,” said Dr. Papa, director of academic clinical research at Orlando (Fla.) Regional Medical Center.

If further study confirms the value of UCH-L1 as the first clinical biomarker in traumatic brain injury (TBI), physicians will be better able to identify targets for drug therapy and guide the timing of treatment with such agents as tissue plasminogen activator, she explained.

This prospective case-control study enrolled consecutive adult patients presenting to two tertiary care teaching hospitals following severe TBIs, defined by a GCS score of less than 8 and requiring invasive intracerebral monitoring.

The primary outcome was severity of injury as measured by postresuscitation and 24-hour dichotomized GCS score. Secondary outcome included the presence of evolving lesions on CT scan at 24 and 72 hours post injury. Over 16 months, 41 patients with severe TBI were enrolled. Their mean age was 38 years, and four-fifths were men. Patients were excluded if they did not have ventriculostomy, which is necessary to obtain cerebrospinal fluid (CSF).

Ventricular CSF was drained from each patient at 6, 12, 24, 48, 72, and 96 hours after TBI and was measured by enzyme-linked immunosorbent assay for UCH-L1 levels.

The control group consisted of uninjured patients who required CSF drainage for other reasons. Mean 12-hour UCH-L1 levels were 145 ng/mL for patients with GCS scores of 3–5, and 38.5 ng/mL in those with GCS scores of 6–8. Similarly, 24-hour levels were 76 and 36 ng/mL for those with GCS scores of 3–5 and 6–8, respectively.

The largest increase in the experimental biomarker occurred during the first 48 hours after injury. “Then we found that patients with evolving lesions had significantly higher levels of the biomarker” than did patients with nonevolving lesions at both 48 and 72 hours, she said.

“There is a significant increase in CSF UCH-L1 following severe human TBI compared to uninjured controls, and there is a significant association with severity of injury as measured by GCS and the presence of evolving lesions on CT,” Dr. Papa said, adding that these data suggest that UCH-L1 is a potential TBI biomarker. Dr. Papa said more than 5 million Americans live with TBI disabilities, and the hospital and fatality costs related to TBI exceed $48 billion annually.

'Patients with evolving lesions had significantly higher levels of the biomarker' after 48 hours. DR. PAPA

CHICAGO – An enzyme found in brain cells may become the first bedside biomarker for assessing the severity of traumatic brain injury, according to Dr. Linda Papa.

In a multicenter trial, levels of the enzyme ubiquitin C-terminal hydrolase (UCH-L1) rose significantly in severely injured brains, an increase that paralleled the rise in cerebral spinal fluid and correlated with the Glasgow Coma Scale (GCS) score, Dr. Papa said at the annual meeting of the Society for Academic Emergency Medicine.

“We know that biomarkers can provide diagnostic and prognostic information, give us insight into the pathophysiology of the brain injury, and guide therapy in both the emergency department and intensive care unit,” said Dr. Papa, director of academic clinical research at Orlando (Fla.) Regional Medical Center.

If further study confirms the value of UCH-L1 as the first clinical biomarker in traumatic brain injury (TBI), physicians will be better able to identify targets for drug therapy and guide the timing of treatment with such agents as tissue plasminogen activator, she explained.

This prospective case-control study enrolled consecutive adult patients presenting to two tertiary care teaching hospitals following severe TBIs, defined by a GCS score of less than 8 and requiring invasive intracerebral monitoring.

The primary outcome was severity of injury as measured by postresuscitation and 24-hour dichotomized GCS score. Secondary outcome included the presence of evolving lesions on CT scan at 24 and 72 hours post injury. Over 16 months, 41 patients with severe TBI were enrolled. Their mean age was 38 years, and four-fifths were men. Patients were excluded if they did not have ventriculostomy, which is necessary to obtain cerebrospinal fluid (CSF).

Ventricular CSF was drained from each patient at 6, 12, 24, 48, 72, and 96 hours after TBI and was measured by enzyme-linked immunosorbent assay for UCH-L1 levels.

The control group consisted of uninjured patients who required CSF drainage for other reasons. Mean 12-hour UCH-L1 levels were 145 ng/mL for patients with GCS scores of 3–5, and 38.5 ng/mL in those with GCS scores of 6–8. Similarly, 24-hour levels were 76 and 36 ng/mL for those with GCS scores of 3–5 and 6–8, respectively.

The largest increase in the experimental biomarker occurred during the first 48 hours after injury. “Then we found that patients with evolving lesions had significantly higher levels of the biomarker” than did patients with nonevolving lesions at both 48 and 72 hours, she said.

“There is a significant increase in CSF UCH-L1 following severe human TBI compared to uninjured controls, and there is a significant association with severity of injury as measured by GCS and the presence of evolving lesions on CT,” Dr. Papa said, adding that these data suggest that UCH-L1 is a potential TBI biomarker. Dr. Papa said more than 5 million Americans live with TBI disabilities, and the hospital and fatality costs related to TBI exceed $48 billion annually.

'Patients with evolving lesions had significantly higher levels of the biomarker' after 48 hours. DR. PAPA

ST. LOUIS – Problematic family functioning merges with children's perceptions of positive and negative reinforcements to produce school refusal behavior, according to research presented at the annual conference of the Anxiety Disorders Association of America.

“It's important that we be aware of the relationship between family environment and school refusal behavior,” said Gillian Chapman, of the University of Nevada, Las Vegas.

“This awareness is an essential step toward our ability to structure appropriate clinical assessment criteria and, ultimately, devise applied and appropriate therapy for children and families with school refusal behavior,” she said.

Ms. Chapman is part of a team of UNLV researchers, led by Christopher A. Kearney, Ph.D., that is investigating the often complicated circumstances that lead to a child's desire to avoid school.

School refusal behavior is an umbrella term that covers many hypothesized subtypes of youths with problematic absenteeism, including truancy, school phobia, and anxiety-based school refusal, explained Dr. Kearney, professor of psychology and director of clinical training at the university.

“Refusal to attend school is a common and urgent problem, and it would benefit clinicians if they had a cookbook reference to help them identify and treat the various forms of this behavior,” he said in an interview.

Through his previous research, Dr. Kearney has concluded that there are four primary functions, or reinforcements, that are the best predictors of absenteeism:

▸ Avoidance of school-related stimuli that provoke negative affectivity. Differential diagnoses or problems include panic disorder and agoraphobia; generalized anxiety disorder; specific phobia; and depression and suicidal behavior.

▸ Desire to escape aversive social and/or evaluative situations. Differential diagnoses or problems include social anxiety disorder, depression, and suicidal behavior.

▸ Pursuit of attention from significant others, usually the parents. Differential diagnoses or problems include separation anxiety disorder, oppositional defiant disorder, and noncompliance in response to most parental commands.

▸ Seeking of tangible reinforcers outside of school (or, it's “more fun” to be outside of school). Differential diagnoses or problems include conduct-disordered behavior such as stealing, setting fires, or aggression; substance abuse; and lack of motivation in many situations.

These reinforcers maintain or reward school refusal behavior. The first two are negative reinforcements (avoidance behavior), and the second two constitute positive reinforcement, Dr. Kearney noted.

The goal of Ms. Chapman's research was to clarify the clinical distinctions among these four functions. She examined the roles of such contributing factors as family cohesion, communication, expressiveness, independence, enmeshment, achievement, and control.

It turned out that family conflict was significantly more common in children who sought reinforcements outside of school and that family enmeshment was more common in attention-seeking children.

Children in well-adjusted, healthy families may exhibit school refusal behavior merely because they're anxious, added Dr. Kearney. “They have good problem-solving and communication skills, but they just don't know how to solve the high anxiety.”

Ms. Chapman also found that children who refuse school to get attention come from more dependent families than do those who refuse school for positive tangible reinforcement, and children who refuse school to avoid stimuli-provoked negative affectivity come from more cohesive families than do those who refuse school for positive tangible reinforcement.

As a group, the 182 families in the study scored below average for independence (that is, they had higher parent-child dependence and overindulgence), she said.

Mean family scores on the cohesion, achievement, intellectual-cultural orientation, active-recreational orientation, and organization subscales were also below normative levels.

Avoidance of school-related stimuli that provoke negative affectivity is just one reinforcer. DR. KEARNEY

ST. LOUIS – Problematic family functioning merges with children's perceptions of positive and negative reinforcements to produce school refusal behavior, according to research presented at the annual conference of the Anxiety Disorders Association of America.

“It's important that we be aware of the relationship between family environment and school refusal behavior,” said Gillian Chapman, of the University of Nevada, Las Vegas.

“This awareness is an essential step toward our ability to structure appropriate clinical assessment criteria and, ultimately, devise applied and appropriate therapy for children and families with school refusal behavior,” she said.

Ms. Chapman is part of a team of UNLV researchers, led by Christopher A. Kearney, Ph.D., that is investigating the often complicated circumstances that lead to a child's desire to avoid school.

School refusal behavior is an umbrella term that covers many hypothesized subtypes of youths with problematic absenteeism, including truancy, school phobia, and anxiety-based school refusal, explained Dr. Kearney, professor of psychology and director of clinical training at the university.

“Refusal to attend school is a common and urgent problem, and it would benefit clinicians if they had a cookbook reference to help them identify and treat the various forms of this behavior,” he said in an interview.

Through his previous research, Dr. Kearney has concluded that there are four primary functions, or reinforcements, that are the best predictors of absenteeism:

▸ Avoidance of school-related stimuli that provoke negative affectivity. Differential diagnoses or problems include panic disorder and agoraphobia; generalized anxiety disorder; specific phobia; and depression and suicidal behavior.

▸ Desire to escape aversive social and/or evaluative situations. Differential diagnoses or problems include social anxiety disorder, depression, and suicidal behavior.

▸ Pursuit of attention from significant others, usually the parents. Differential diagnoses or problems include separation anxiety disorder, oppositional defiant disorder, and noncompliance in response to most parental commands.

▸ Seeking of tangible reinforcers outside of school (or, it's “more fun” to be outside of school). Differential diagnoses or problems include conduct-disordered behavior such as stealing, setting fires, or aggression; substance abuse; and lack of motivation in many situations.

These reinforcers maintain or reward school refusal behavior. The first two are negative reinforcements (avoidance behavior), and the second two constitute positive reinforcement, Dr. Kearney noted.

The goal of Ms. Chapman's research was to clarify the clinical distinctions among these four functions. She examined the roles of such contributing factors as family cohesion, communication, expressiveness, independence, enmeshment, achievement, and control.

It turned out that family conflict was significantly more common in children who sought reinforcements outside of school and that family enmeshment was more common in attention-seeking children.

Children in well-adjusted, healthy families may exhibit school refusal behavior merely because they're anxious, added Dr. Kearney. “They have good problem-solving and communication skills, but they just don't know how to solve the high anxiety.”

Ms. Chapman also found that children who refuse school to get attention come from more dependent families than do those who refuse school for positive tangible reinforcement, and children who refuse school to avoid stimuli-provoked negative affectivity come from more cohesive families than do those who refuse school for positive tangible reinforcement.

As a group, the 182 families in the study scored below average for independence (that is, they had higher parent-child dependence and overindulgence), she said.

Mean family scores on the cohesion, achievement, intellectual-cultural orientation, active-recreational orientation, and organization subscales were also below normative levels.

Avoidance of school-related stimuli that provoke negative affectivity is just one reinforcer. DR. KEARNEY

ST. LOUIS – Problematic family functioning merges with children's perceptions of positive and negative reinforcements to produce school refusal behavior, according to research presented at the annual conference of the Anxiety Disorders Association of America.

“It's important that we be aware of the relationship between family environment and school refusal behavior,” said Gillian Chapman, of the University of Nevada, Las Vegas.

“This awareness is an essential step toward our ability to structure appropriate clinical assessment criteria and, ultimately, devise applied and appropriate therapy for children and families with school refusal behavior,” she said.

Ms. Chapman is part of a team of UNLV researchers, led by Christopher A. Kearney, Ph.D., that is investigating the often complicated circumstances that lead to a child's desire to avoid school.

School refusal behavior is an umbrella term that covers many hypothesized subtypes of youths with problematic absenteeism, including truancy, school phobia, and anxiety-based school refusal, explained Dr. Kearney, professor of psychology and director of clinical training at the university.

“Refusal to attend school is a common and urgent problem, and it would benefit clinicians if they had a cookbook reference to help them identify and treat the various forms of this behavior,” he said in an interview.

Through his previous research, Dr. Kearney has concluded that there are four primary functions, or reinforcements, that are the best predictors of absenteeism:

▸ Avoidance of school-related stimuli that provoke negative affectivity. Differential diagnoses or problems include panic disorder and agoraphobia; generalized anxiety disorder; specific phobia; and depression and suicidal behavior.

▸ Desire to escape aversive social and/or evaluative situations. Differential diagnoses or problems include social anxiety disorder, depression, and suicidal behavior.

▸ Pursuit of attention from significant others, usually the parents. Differential diagnoses or problems include separation anxiety disorder, oppositional defiant disorder, and noncompliance in response to most parental commands.

▸ Seeking of tangible reinforcers outside of school (or, it's “more fun” to be outside of school). Differential diagnoses or problems include conduct-disordered behavior such as stealing, setting fires, or aggression; substance abuse; and lack of motivation in many situations.

These reinforcers maintain or reward school refusal behavior. The first two are negative reinforcements (avoidance behavior), and the second two constitute positive reinforcement, Dr. Kearney noted.

The goal of Ms. Chapman's research was to clarify the clinical distinctions among these four functions. She examined the roles of such contributing factors as family cohesion, communication, expressiveness, independence, enmeshment, achievement, and control.

It turned out that family conflict was significantly more common in children who sought reinforcements outside of school and that family enmeshment was more common in attention-seeking children.

Children in well-adjusted, healthy families may exhibit school refusal behavior merely because they're anxious, added Dr. Kearney. “They have good problem-solving and communication skills, but they just don't know how to solve the high anxiety.”

Ms. Chapman also found that children who refuse school to get attention come from more dependent families than do those who refuse school for positive tangible reinforcement, and children who refuse school to avoid stimuli-provoked negative affectivity come from more cohesive families than do those who refuse school for positive tangible reinforcement.

As a group, the 182 families in the study scored below average for independence (that is, they had higher parent-child dependence and overindulgence), she said.

Mean family scores on the cohesion, achievement, intellectual-cultural orientation, active-recreational orientation, and organization subscales were also below normative levels.

Avoidance of school-related stimuli that provoke negative affectivity is just one reinforcer. DR. KEARNEY

ST. LOUIS — The experimental concept of improving the treatment of anxiety disorders by combining exposure therapy with a medication has received a boost from two pilot studies presented at the annual conference of the Anxiety Disorders Association of America.

In one study, investigators found that D-cycloserine for obsessive-compulsive disorder (OCD) increases therapeutic learning, accelerates fear extinction in early sessions, and reduces the number of exposure sessions required for a good outcome, reported Matt Kushner, Ph.D., a professor of psychiatry at the University of Minnesota, Minneapolis.

A second, already published study achieved better long-term results in the treatment of social anxiety disorder (Arch. Gen. Psychiatry 2006;63:298–304).

These studies provide preliminary support for the use of short-term dosing of D-cycloserine as an adjunctive intervention to exposure therapy for social anxiety disorder, said Stefan G. Hofmann, Ph.D., lead author of the second study.

“This giving a pill to enhance psychotherapy is a paradigm shift in the treatment of anxiety disorders,” commented Dr. Hofmann, professor of psychology and director of the social anxiety program at the Center for Anxiety and Related Disorders at Boston University.

D-Cycloserine, an agonist at the glutamatergic N-methyl-D-aspartate (NMDA) receptor, had been shown to improve the effectiveness of exposure therapy of acrophobia in an earlier pilot study (Arch. Gen. Psychiatry 2004;61:1136–44), and has successfully promoted the extinction of conditioned fear in several other animal studies.

By itself, exposure therapy for OCD has significant limitations, Dr. Kushner said. “It's difficult in that the patient must repeatedly face his or her worst fears. It's time consuming, and it's expensive,” he said, adding that exposure therapy has a refusal/dropout rate approaching 25% and an overall effectiveness rate of less than 50%.

To test the hypothesis that D-cycloserine (DCS) augmentation would raise the effectiveness ceiling of exposure therapy for OCD, Dr. Kushner and his team conducted a double-blind study of 32 subjects with the compulsive rituals of washing or checking.

Half received exposure therapy plus 125 mg DCS twice weekly; the second group received exposure therapy plus placebo. Subjects were allowed to be on a stable dose of psychiatric medications other than benzodiazepines.

All of the subjects received four sessions of exposure and ritual prevention twice weekly.

After four sessions of therapy, the patients were allowed to continue until they had a 50% reduction in symptoms, or until session 10, whichever came first.

This criterion was met by session 10 in 40% of the placebo group and 80% of the DCS group, though the learning effects of the drug diminished after the fourth session.

Dr. Kushner said the most striking finding was that extinction learning from DCS did improve retention, in that less than 7% of those receiving DCS blindly dropped out of the study, compared with one-third of those in the placebo group.

He said he interpreted that to mean that there was a greater effort-to-benefit ratio with dual therapy.

“People tend to stay in therapy and work hard when the early results are good,” he said.

In the social anxiety disorder study, 27 participants received five therapy sessions delivered in either individual or group therapy format. The first session introduced the treatment model and was followed by four sessions emphasizing exposure to increasingly challenging public speaking situations.

An hour before each session, participants received single 50-mg doses of D-cycloserine or placebo.

Symptoms were assessed by patient self-report and by clinicians blind to the rand- omization condition before and after treatment and 1 month after the last session.

Assessments were made using the Social Phobia and Anxiety Inventory, the Liebowitz Social Anxiety Scale, and the Clinical Global Impression Scale. Those receiving D-cycloserine in addition to exposure therapy reported significantly less social anxiety, compared with those in the exposure therapy plus placebo group.

On follow-up, no drop-off was found in fear extinction such as was seen in Dr. Kushner's OCD study.

“It may be that in a dosing regimen such as was used in our study, there's an accumulation of D-cycloserine—which causes it to switch from being an NMDA receptor agonist to an NMDA antagonist, as has been shown in animal studies,” Dr. Kushner said in an interview. “So the drug may be counterproductive at higher doses.”

Dr. Kushner added that his results might have been better had he given the medication as Dr. Hofmann had, 50 mg at weekly intervals.

'People tend to stay in therapy and work hard when the early results are good.' DR. KUSHNER

ST. LOUIS — The experimental concept of improving the treatment of anxiety disorders by combining exposure therapy with a medication has received a boost from two pilot studies presented at the annual conference of the Anxiety Disorders Association of America.

In one study, investigators found that D-cycloserine for obsessive-compulsive disorder (OCD) increases therapeutic learning, accelerates fear extinction in early sessions, and reduces the number of exposure sessions required for a good outcome, reported Matt Kushner, Ph.D., a professor of psychiatry at the University of Minnesota, Minneapolis.

A second, already published study achieved better long-term results in the treatment of social anxiety disorder (Arch. Gen. Psychiatry 2006;63:298–304).

These studies provide preliminary support for the use of short-term dosing of D-cycloserine as an adjunctive intervention to exposure therapy for social anxiety disorder, said Stefan G. Hofmann, Ph.D., lead author of the second study.

“This giving a pill to enhance psychotherapy is a paradigm shift in the treatment of anxiety disorders,” commented Dr. Hofmann, professor of psychology and director of the social anxiety program at the Center for Anxiety and Related Disorders at Boston University.

D-Cycloserine, an agonist at the glutamatergic N-methyl-D-aspartate (NMDA) receptor, had been shown to improve the effectiveness of exposure therapy of acrophobia in an earlier pilot study (Arch. Gen. Psychiatry 2004;61:1136–44), and has successfully promoted the extinction of conditioned fear in several other animal studies.

By itself, exposure therapy for OCD has significant limitations, Dr. Kushner said. “It's difficult in that the patient must repeatedly face his or her worst fears. It's time consuming, and it's expensive,” he said, adding that exposure therapy has a refusal/dropout rate approaching 25% and an overall effectiveness rate of less than 50%.

To test the hypothesis that D-cycloserine (DCS) augmentation would raise the effectiveness ceiling of exposure therapy for OCD, Dr. Kushner and his team conducted a double-blind study of 32 subjects with the compulsive rituals of washing or checking.

Half received exposure therapy plus 125 mg DCS twice weekly; the second group received exposure therapy plus placebo. Subjects were allowed to be on a stable dose of psychiatric medications other than benzodiazepines.

All of the subjects received four sessions of exposure and ritual prevention twice weekly.

After four sessions of therapy, the patients were allowed to continue until they had a 50% reduction in symptoms, or until session 10, whichever came first.

This criterion was met by session 10 in 40% of the placebo group and 80% of the DCS group, though the learning effects of the drug diminished after the fourth session.

Dr. Kushner said the most striking finding was that extinction learning from DCS did improve retention, in that less than 7% of those receiving DCS blindly dropped out of the study, compared with one-third of those in the placebo group.

He said he interpreted that to mean that there was a greater effort-to-benefit ratio with dual therapy.

“People tend to stay in therapy and work hard when the early results are good,” he said.

In the social anxiety disorder study, 27 participants received five therapy sessions delivered in either individual or group therapy format. The first session introduced the treatment model and was followed by four sessions emphasizing exposure to increasingly challenging public speaking situations.

An hour before each session, participants received single 50-mg doses of D-cycloserine or placebo.

Symptoms were assessed by patient self-report and by clinicians blind to the rand- omization condition before and after treatment and 1 month after the last session.

Assessments were made using the Social Phobia and Anxiety Inventory, the Liebowitz Social Anxiety Scale, and the Clinical Global Impression Scale. Those receiving D-cycloserine in addition to exposure therapy reported significantly less social anxiety, compared with those in the exposure therapy plus placebo group.

On follow-up, no drop-off was found in fear extinction such as was seen in Dr. Kushner's OCD study.

“It may be that in a dosing regimen such as was used in our study, there's an accumulation of D-cycloserine—which causes it to switch from being an NMDA receptor agonist to an NMDA antagonist, as has been shown in animal studies,” Dr. Kushner said in an interview. “So the drug may be counterproductive at higher doses.”

Dr. Kushner added that his results might have been better had he given the medication as Dr. Hofmann had, 50 mg at weekly intervals.

'People tend to stay in therapy and work hard when the early results are good.' DR. KUSHNER

ST. LOUIS — The experimental concept of improving the treatment of anxiety disorders by combining exposure therapy with a medication has received a boost from two pilot studies presented at the annual conference of the Anxiety Disorders Association of America.

In one study, investigators found that D-cycloserine for obsessive-compulsive disorder (OCD) increases therapeutic learning, accelerates fear extinction in early sessions, and reduces the number of exposure sessions required for a good outcome, reported Matt Kushner, Ph.D., a professor of psychiatry at the University of Minnesota, Minneapolis.

A second, already published study achieved better long-term results in the treatment of social anxiety disorder (Arch. Gen. Psychiatry 2006;63:298–304).

These studies provide preliminary support for the use of short-term dosing of D-cycloserine as an adjunctive intervention to exposure therapy for social anxiety disorder, said Stefan G. Hofmann, Ph.D., lead author of the second study.

“This giving a pill to enhance psychotherapy is a paradigm shift in the treatment of anxiety disorders,” commented Dr. Hofmann, professor of psychology and director of the social anxiety program at the Center for Anxiety and Related Disorders at Boston University.

D-Cycloserine, an agonist at the glutamatergic N-methyl-D-aspartate (NMDA) receptor, had been shown to improve the effectiveness of exposure therapy of acrophobia in an earlier pilot study (Arch. Gen. Psychiatry 2004;61:1136–44), and has successfully promoted the extinction of conditioned fear in several other animal studies.

By itself, exposure therapy for OCD has significant limitations, Dr. Kushner said. “It's difficult in that the patient must repeatedly face his or her worst fears. It's time consuming, and it's expensive,” he said, adding that exposure therapy has a refusal/dropout rate approaching 25% and an overall effectiveness rate of less than 50%.

To test the hypothesis that D-cycloserine (DCS) augmentation would raise the effectiveness ceiling of exposure therapy for OCD, Dr. Kushner and his team conducted a double-blind study of 32 subjects with the compulsive rituals of washing or checking.

Half received exposure therapy plus 125 mg DCS twice weekly; the second group received exposure therapy plus placebo. Subjects were allowed to be on a stable dose of psychiatric medications other than benzodiazepines.

All of the subjects received four sessions of exposure and ritual prevention twice weekly.

After four sessions of therapy, the patients were allowed to continue until they had a 50% reduction in symptoms, or until session 10, whichever came first.

This criterion was met by session 10 in 40% of the placebo group and 80% of the DCS group, though the learning effects of the drug diminished after the fourth session.

Dr. Kushner said the most striking finding was that extinction learning from DCS did improve retention, in that less than 7% of those receiving DCS blindly dropped out of the study, compared with one-third of those in the placebo group.

He said he interpreted that to mean that there was a greater effort-to-benefit ratio with dual therapy.

“People tend to stay in therapy and work hard when the early results are good,” he said.

In the social anxiety disorder study, 27 participants received five therapy sessions delivered in either individual or group therapy format. The first session introduced the treatment model and was followed by four sessions emphasizing exposure to increasingly challenging public speaking situations.

An hour before each session, participants received single 50-mg doses of D-cycloserine or placebo.

Symptoms were assessed by patient self-report and by clinicians blind to the rand- omization condition before and after treatment and 1 month after the last session.

Assessments were made using the Social Phobia and Anxiety Inventory, the Liebowitz Social Anxiety Scale, and the Clinical Global Impression Scale. Those receiving D-cycloserine in addition to exposure therapy reported significantly less social anxiety, compared with those in the exposure therapy plus placebo group.

On follow-up, no drop-off was found in fear extinction such as was seen in Dr. Kushner's OCD study.

“It may be that in a dosing regimen such as was used in our study, there's an accumulation of D-cycloserine—which causes it to switch from being an NMDA receptor agonist to an NMDA antagonist, as has been shown in animal studies,” Dr. Kushner said in an interview. “So the drug may be counterproductive at higher doses.”

Dr. Kushner added that his results might have been better had he given the medication as Dr. Hofmann had, 50 mg at weekly intervals.

'People tend to stay in therapy and work hard when the early results are good.' DR. KUSHNER

Patients with type 1 diabetes may be better protected from diabetic macular edema by improved control of glycemia, LDL cholesterol levels, and blood pressure, according to a 15-year follow-up study.

The prospective study was launched in 1990 with a cohort of 112 consecutive type 1 diabetes patients who did not have diabetic retinopathy or nephropathy at the time, according to Dr. Pedro Romero and colleagues at the Hospital Universitario Sant Joan de Reus, Universidad Rovira y Virgili, Spain.

“Our objective was to determine the epidemiological risk factors that influence the development of diabetic macular edema, in particular renal diabetic lesion (microalbuminuria or overt nephropathy),” the authors wrote in the Journal of Diabetes and Its Complications.

The half-male, half-female cohort had a mean age of 40 years and a mean diabetes duration of 23.4 years. Arterial hypertension was present in 39% of the patients.

Diabetic retinopathy was evaluated by photographs, through dilated pupils, of two 50-degree fields of each eye centered. The results were then classified as mild nonproliferative, moderate proliferative, severe proliferative, and proliferative (J. Diabetes Complications 2007;21:172–80).

Macular edema was considered present when retinal thickening involved or was within 500 mcm of the center of the macula; when hard exudates were at or within 500 mcm of the macula, if it was associated with a thickening of the adjacent retina (but no hard exudates remained after retinal thickening disappeared); and when the zone(s) of retinal thickening was (were) one disc area (or larger) in size, any part of which was within one disc diameter of the center of the macula.

The clinical classification used was the International Clinical Diabetic Retinopathy Disease Severity Scale, the investigators wrote.

After 15 years, one-half of the cohort had diabetic retinopathy (DR) and one-fifth of the cohort had diabetic macular edema (DME). More than half of those with DME had the focal type, a third were the diffuse form, and two patients had diffuse associated form to cystoid form (which is associated with diffuse form).

The mean visual acuity in patients with DME after 15 years was 0.31 in the Snellen chart test and 1.26 in the LogMAR test. The mean macular thickness was 356.21.

Factors found to be significant to the development of DME included:

▸ High levels of glycated hemoglobin. Glycemic control was classified into two groups: hemoglobin A_1c greater than 7.5% or less than 7.5% in concordance with the European Diabetes Policy Group. The value included in statistical analyses was the mean of all values obtained over the trial period.

▸ High levels of LDL cholesterol as defined by the American Diabetes Association categories (3.35 mmol/L or higher). In contrast to previous published research, no lipid parameters were associated with the progression of diabetic retinopathy or with proliferative diabetic retinopathy after adjustment for glycated hemoglobin and other risk factors, the investigators explained.

▸ The presence of macroangiopathy. For this, one or more of the following had to be present: symptoms of angina pectoris, history of myocardial infarction, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, symptoms of or operation for intermittent claudication, history of amputation, transient ischemic attack, and stroke.

The authors maintained that this relationship between macroangiopathy and DME “may be explained, in part, by the increased incidence of macular edema with increased levels of lipids, which was strongly associated with the development of macroangiopathic lesions in” previous studies (Br. J. Ophthalmol. 2002;86:84–90; Ophthalmology 2002;109:1225–34).

▸ The presence of arterial hypertension, defined as a systolic measurement of 140 mm Hg or higher and a diastolic measurement of 90 mm Hg or higher.

This result contradicted an earlier finding from a 10-year study showing that the level of diastolic blood pressure was not a predictor in type 1 diabetes patients (Arch. Ophthalmol. 1995;113:601–6).

“However, a precedent study of that same group, at four years, found a positive relationship between diastolic blood pressure and the incidence of macular edema,” wrote Dr. Romero and his colleagues.

▸ The severity of diabetic retinopathy, a finding which confirms previous studies.

The researchers expressed surprise that the study found no association with cigarette smoking, although an earlier study also failed to link cigarette smoking with DME (Ophthalmology 1996;103:1438–42). The current investigators hypothesize that cigarette smoking, through its deleterious effects on the retinal vasculature, may affect diabetic maculopathy.

“We did not demonstrate this effect, but if we had studied the angiographic findings in patients with diabetic macular edema, we may not have associated cigarette smoking with an increase in the development of areas of macular ischemia,” they said.

“Our data suggest that better control of glycemia, LDL cholesterol levels, and blood pressure in type 1 diabetes patients may be beneficial in reducing the incidence of diabetic macular edema,” the researchers concluded, adding that their results validate the current guidelines for ophthalmologic care for the detection of diabetic macular edema over the long-term course of diabetes.

Patients with type 1 diabetes may be better protected from diabetic macular edema by improved control of glycemia, LDL cholesterol levels, and blood pressure, according to a 15-year follow-up study.

The prospective study was launched in 1990 with a cohort of 112 consecutive type 1 diabetes patients who did not have diabetic retinopathy or nephropathy at the time, according to Dr. Pedro Romero and colleagues at the Hospital Universitario Sant Joan de Reus, Universidad Rovira y Virgili, Spain.

“Our objective was to determine the epidemiological risk factors that influence the development of diabetic macular edema, in particular renal diabetic lesion (microalbuminuria or overt nephropathy),” the authors wrote in the Journal of Diabetes and Its Complications.

The half-male, half-female cohort had a mean age of 40 years and a mean diabetes duration of 23.4 years. Arterial hypertension was present in 39% of the patients.

Diabetic retinopathy was evaluated by photographs, through dilated pupils, of two 50-degree fields of each eye centered. The results were then classified as mild nonproliferative, moderate proliferative, severe proliferative, and proliferative (J. Diabetes Complications 2007;21:172–80).

Macular edema was considered present when retinal thickening involved or was within 500 mcm of the center of the macula; when hard exudates were at or within 500 mcm of the macula, if it was associated with a thickening of the adjacent retina (but no hard exudates remained after retinal thickening disappeared); and when the zone(s) of retinal thickening was (were) one disc area (or larger) in size, any part of which was within one disc diameter of the center of the macula.

The clinical classification used was the International Clinical Diabetic Retinopathy Disease Severity Scale, the investigators wrote.

After 15 years, one-half of the cohort had diabetic retinopathy (DR) and one-fifth of the cohort had diabetic macular edema (DME). More than half of those with DME had the focal type, a third were the diffuse form, and two patients had diffuse associated form to cystoid form (which is associated with diffuse form).

The mean visual acuity in patients with DME after 15 years was 0.31 in the Snellen chart test and 1.26 in the LogMAR test. The mean macular thickness was 356.21.

Factors found to be significant to the development of DME included:

▸ High levels of glycated hemoglobin. Glycemic control was classified into two groups: hemoglobin A_1c greater than 7.5% or less than 7.5% in concordance with the European Diabetes Policy Group. The value included in statistical analyses was the mean of all values obtained over the trial period.

▸ High levels of LDL cholesterol as defined by the American Diabetes Association categories (3.35 mmol/L or higher). In contrast to previous published research, no lipid parameters were associated with the progression of diabetic retinopathy or with proliferative diabetic retinopathy after adjustment for glycated hemoglobin and other risk factors, the investigators explained.

▸ The presence of macroangiopathy. For this, one or more of the following had to be present: symptoms of angina pectoris, history of myocardial infarction, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, symptoms of or operation for intermittent claudication, history of amputation, transient ischemic attack, and stroke.

The authors maintained that this relationship between macroangiopathy and DME “may be explained, in part, by the increased incidence of macular edema with increased levels of lipids, which was strongly associated with the development of macroangiopathic lesions in” previous studies (Br. J. Ophthalmol. 2002;86:84–90; Ophthalmology 2002;109:1225–34).

▸ The presence of arterial hypertension, defined as a systolic measurement of 140 mm Hg or higher and a diastolic measurement of 90 mm Hg or higher.

This result contradicted an earlier finding from a 10-year study showing that the level of diastolic blood pressure was not a predictor in type 1 diabetes patients (Arch. Ophthalmol. 1995;113:601–6).

“However, a precedent study of that same group, at four years, found a positive relationship between diastolic blood pressure and the incidence of macular edema,” wrote Dr. Romero and his colleagues.

▸ The severity of diabetic retinopathy, a finding which confirms previous studies.

The researchers expressed surprise that the study found no association with cigarette smoking, although an earlier study also failed to link cigarette smoking with DME (Ophthalmology 1996;103:1438–42). The current investigators hypothesize that cigarette smoking, through its deleterious effects on the retinal vasculature, may affect diabetic maculopathy.

“We did not demonstrate this effect, but if we had studied the angiographic findings in patients with diabetic macular edema, we may not have associated cigarette smoking with an increase in the development of areas of macular ischemia,” they said.

“Our data suggest that better control of glycemia, LDL cholesterol levels, and blood pressure in type 1 diabetes patients may be beneficial in reducing the incidence of diabetic macular edema,” the researchers concluded, adding that their results validate the current guidelines for ophthalmologic care for the detection of diabetic macular edema over the long-term course of diabetes.

Patients with type 1 diabetes may be better protected from diabetic macular edema by improved control of glycemia, LDL cholesterol levels, and blood pressure, according to a 15-year follow-up study.

The prospective study was launched in 1990 with a cohort of 112 consecutive type 1 diabetes patients who did not have diabetic retinopathy or nephropathy at the time, according to Dr. Pedro Romero and colleagues at the Hospital Universitario Sant Joan de Reus, Universidad Rovira y Virgili, Spain.

“Our objective was to determine the epidemiological risk factors that influence the development of diabetic macular edema, in particular renal diabetic lesion (microalbuminuria or overt nephropathy),” the authors wrote in the Journal of Diabetes and Its Complications.

The half-male, half-female cohort had a mean age of 40 years and a mean diabetes duration of 23.4 years. Arterial hypertension was present in 39% of the patients.

Diabetic retinopathy was evaluated by photographs, through dilated pupils, of two 50-degree fields of each eye centered. The results were then classified as mild nonproliferative, moderate proliferative, severe proliferative, and proliferative (J. Diabetes Complications 2007;21:172–80).

Macular edema was considered present when retinal thickening involved or was within 500 mcm of the center of the macula; when hard exudates were at or within 500 mcm of the macula, if it was associated with a thickening of the adjacent retina (but no hard exudates remained after retinal thickening disappeared); and when the zone(s) of retinal thickening was (were) one disc area (or larger) in size, any part of which was within one disc diameter of the center of the macula.

The clinical classification used was the International Clinical Diabetic Retinopathy Disease Severity Scale, the investigators wrote.

After 15 years, one-half of the cohort had diabetic retinopathy (DR) and one-fifth of the cohort had diabetic macular edema (DME). More than half of those with DME had the focal type, a third were the diffuse form, and two patients had diffuse associated form to cystoid form (which is associated with diffuse form).

The mean visual acuity in patients with DME after 15 years was 0.31 in the Snellen chart test and 1.26 in the LogMAR test. The mean macular thickness was 356.21.

Factors found to be significant to the development of DME included:

▸ High levels of glycated hemoglobin. Glycemic control was classified into two groups: hemoglobin A_1c greater than 7.5% or less than 7.5% in concordance with the European Diabetes Policy Group. The value included in statistical analyses was the mean of all values obtained over the trial period.

▸ High levels of LDL cholesterol as defined by the American Diabetes Association categories (3.35 mmol/L or higher). In contrast to previous published research, no lipid parameters were associated with the progression of diabetic retinopathy or with proliferative diabetic retinopathy after adjustment for glycated hemoglobin and other risk factors, the investigators explained.

▸ The presence of macroangiopathy. For this, one or more of the following had to be present: symptoms of angina pectoris, history of myocardial infarction, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, symptoms of or operation for intermittent claudication, history of amputation, transient ischemic attack, and stroke.

The authors maintained that this relationship between macroangiopathy and DME “may be explained, in part, by the increased incidence of macular edema with increased levels of lipids, which was strongly associated with the development of macroangiopathic lesions in” previous studies (Br. J. Ophthalmol. 2002;86:84–90; Ophthalmology 2002;109:1225–34).

▸ The presence of arterial hypertension, defined as a systolic measurement of 140 mm Hg or higher and a diastolic measurement of 90 mm Hg or higher.

This result contradicted an earlier finding from a 10-year study showing that the level of diastolic blood pressure was not a predictor in type 1 diabetes patients (Arch. Ophthalmol. 1995;113:601–6).

“However, a precedent study of that same group, at four years, found a positive relationship between diastolic blood pressure and the incidence of macular edema,” wrote Dr. Romero and his colleagues.

▸ The severity of diabetic retinopathy, a finding which confirms previous studies.

The researchers expressed surprise that the study found no association with cigarette smoking, although an earlier study also failed to link cigarette smoking with DME (Ophthalmology 1996;103:1438–42). The current investigators hypothesize that cigarette smoking, through its deleterious effects on the retinal vasculature, may affect diabetic maculopathy.

“We did not demonstrate this effect, but if we had studied the angiographic findings in patients with diabetic macular edema, we may not have associated cigarette smoking with an increase in the development of areas of macular ischemia,” they said.

“Our data suggest that better control of glycemia, LDL cholesterol levels, and blood pressure in type 1 diabetes patients may be beneficial in reducing the incidence of diabetic macular edema,” the researchers concluded, adding that their results validate the current guidelines for ophthalmologic care for the detection of diabetic macular edema over the long-term course of diabetes.