Neil Osterweil

BOSTON – Preoperative comorbidities and postoperative complications are the most common reasons that patients are readmitted to a hospital within 30 days of thyroid or parathyroid surgery, but outpatient surgery was associated with a lower likelihood of readmission, investigators have found.

A review of data on more than 7,000 patients who underwent cervical endocrine resections showed that 4% were readmitted within a month of surgery, reported Dr. Matthew G. Mullen, a surgery resident at the University of Virginia Health System in Charlottesville.

"Identifying best practice patterns to avoid major postoperative complications will help reduce hospital readmission rates and improve the quality of patient care," Dr. Mullen said at the annual meeting of the American Association of Endocrine Surgeons.

Previous single-institution studies have shown readmission rates for patients undergoing thyroidectomy of 0.3%-3.9%. A 2010 study of readmission rates among elderly patients undergoing thyroidectomy for thyroid cancer found that 8% required readmission within a month of surgery, Dr. Mullen noted.

To see whether, as they suspected, patients with more medical comorbidities and postoperative complications are more likely to be back in the hospital within 30 days of surgery, the investigators reviewed the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) participant use data file, which includes records on 442,149 elective surgery cases from 315 U.S. hospitals. Data on a total of 7,069 total elective cases, including 3,711 thyroidectomies and 3,358 parathyroidectomies were reviewed.

They found an overall readmission rate of 4.0%, with a rate of 4.1% for patients undergoing thyroidectomy, and 3.8% for those undergoing parathyroidectomy.

Demographic factors significantly associated with a greater likelihood of readmission included diabetes (present in 18.6% of readmitted patients, vs. 12.5% of not readmitted patients; P = .003), severe chronic obstructive pulmonary disease (4.6% vs. 2.0%; P = .002), hemodialysis (11.8% vs. 2.2%; P = .001), and weight loss of more than 10% (1.8% vs. 0.5%; P = .005). Younger and heavier patients were more likely to be readmitted within 30 days than were slightly older and lighter-weight patients.

Complications predict readmission

Postoperative complications associated with readmission included wound complications (5% vs. 0.3%; P less than .001 for all following comparisons, unless noted), respiratory complications 5.4 vs. 0.2%), renal complications (2.1% vs. 0.3%), neurologic complications (0.7% vs. 0.1%; P = .008), and cardiovascular complications (4.6% vs. 0.2%).

In multivariate analysis, factors that were significantly associated with readmission were reoperation within 30 days (P less than .001), American Society of Anesthesiologists physical status class (P = .024), patient functional status (independent vs. partially or fully dependent, P = .007), renal insufficiency (P = .004), and hemodialysis (P = .005).

In contrast, patients who were discharged within 24 hours of surgery were significantly less likely to be readmitted (odds ratio, 0.63; P = .006).

The researchers also found that 63% of patients had a longer than 24-hour stay after surgery – a finding that Dr. Mullen said was surprising – and that patients undergoing surgery for malignant disease were significantly more likely to be readmitted than were patients with benign disease (11% vs. 2.6%, P less than .001). There was no difference in readmission rates of patients treated by general surgeons, compared with those treated by surgeons trained in otolaryngologic procedures.

Dr. Mullen noted that the study was limited by the lack of data on the reasons for each readmission and by a lack of information on many complications that are specific to endocrine surgery.

In the discussion, Dr. Samuel K. Snyder of Texas A & M University in Temple, commented on the lack of study specifics about the reasons for readmission making it hard to draw conclusions about how best to prevent readmissions.

Dr. Mullen responded that because some of the patients had treatable comorbidities such as renal insufficiency, medical augmentation could be a reasonable approach to reducing postoperative complications and risk of readmission.

The authors did not disclose the study funding source. Dr. Mullen and Dr. Snyder reported having no financial disclosures.

BOSTON – Preoperative comorbidities and postoperative complications are the most common reasons that patients are readmitted to a hospital within 30 days of thyroid or parathyroid surgery, but outpatient surgery was associated with a lower likelihood of readmission, investigators have found.

A review of data on more than 7,000 patients who underwent cervical endocrine resections showed that 4% were readmitted within a month of surgery, reported Dr. Matthew G. Mullen, a surgery resident at the University of Virginia Health System in Charlottesville.

"Identifying best practice patterns to avoid major postoperative complications will help reduce hospital readmission rates and improve the quality of patient care," Dr. Mullen said at the annual meeting of the American Association of Endocrine Surgeons.

Previous single-institution studies have shown readmission rates for patients undergoing thyroidectomy of 0.3%-3.9%. A 2010 study of readmission rates among elderly patients undergoing thyroidectomy for thyroid cancer found that 8% required readmission within a month of surgery, Dr. Mullen noted.

To see whether, as they suspected, patients with more medical comorbidities and postoperative complications are more likely to be back in the hospital within 30 days of surgery, the investigators reviewed the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) participant use data file, which includes records on 442,149 elective surgery cases from 315 U.S. hospitals. Data on a total of 7,069 total elective cases, including 3,711 thyroidectomies and 3,358 parathyroidectomies were reviewed.

They found an overall readmission rate of 4.0%, with a rate of 4.1% for patients undergoing thyroidectomy, and 3.8% for those undergoing parathyroidectomy.

Demographic factors significantly associated with a greater likelihood of readmission included diabetes (present in 18.6% of readmitted patients, vs. 12.5% of not readmitted patients; P = .003), severe chronic obstructive pulmonary disease (4.6% vs. 2.0%; P = .002), hemodialysis (11.8% vs. 2.2%; P = .001), and weight loss of more than 10% (1.8% vs. 0.5%; P = .005). Younger and heavier patients were more likely to be readmitted within 30 days than were slightly older and lighter-weight patients.

Complications predict readmission

Postoperative complications associated with readmission included wound complications (5% vs. 0.3%; P less than .001 for all following comparisons, unless noted), respiratory complications 5.4 vs. 0.2%), renal complications (2.1% vs. 0.3%), neurologic complications (0.7% vs. 0.1%; P = .008), and cardiovascular complications (4.6% vs. 0.2%).

In multivariate analysis, factors that were significantly associated with readmission were reoperation within 30 days (P less than .001), American Society of Anesthesiologists physical status class (P = .024), patient functional status (independent vs. partially or fully dependent, P = .007), renal insufficiency (P = .004), and hemodialysis (P = .005).

In contrast, patients who were discharged within 24 hours of surgery were significantly less likely to be readmitted (odds ratio, 0.63; P = .006).

The researchers also found that 63% of patients had a longer than 24-hour stay after surgery – a finding that Dr. Mullen said was surprising – and that patients undergoing surgery for malignant disease were significantly more likely to be readmitted than were patients with benign disease (11% vs. 2.6%, P less than .001). There was no difference in readmission rates of patients treated by general surgeons, compared with those treated by surgeons trained in otolaryngologic procedures.

Dr. Mullen noted that the study was limited by the lack of data on the reasons for each readmission and by a lack of information on many complications that are specific to endocrine surgery.

In the discussion, Dr. Samuel K. Snyder of Texas A & M University in Temple, commented on the lack of study specifics about the reasons for readmission making it hard to draw conclusions about how best to prevent readmissions.

Dr. Mullen responded that because some of the patients had treatable comorbidities such as renal insufficiency, medical augmentation could be a reasonable approach to reducing postoperative complications and risk of readmission.

The authors did not disclose the study funding source. Dr. Mullen and Dr. Snyder reported having no financial disclosures.

BOSTON – Preoperative comorbidities and postoperative complications are the most common reasons that patients are readmitted to a hospital within 30 days of thyroid or parathyroid surgery, but outpatient surgery was associated with a lower likelihood of readmission, investigators have found.

A review of data on more than 7,000 patients who underwent cervical endocrine resections showed that 4% were readmitted within a month of surgery, reported Dr. Matthew G. Mullen, a surgery resident at the University of Virginia Health System in Charlottesville.

"Identifying best practice patterns to avoid major postoperative complications will help reduce hospital readmission rates and improve the quality of patient care," Dr. Mullen said at the annual meeting of the American Association of Endocrine Surgeons.

Previous single-institution studies have shown readmission rates for patients undergoing thyroidectomy of 0.3%-3.9%. A 2010 study of readmission rates among elderly patients undergoing thyroidectomy for thyroid cancer found that 8% required readmission within a month of surgery, Dr. Mullen noted.

To see whether, as they suspected, patients with more medical comorbidities and postoperative complications are more likely to be back in the hospital within 30 days of surgery, the investigators reviewed the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) participant use data file, which includes records on 442,149 elective surgery cases from 315 U.S. hospitals. Data on a total of 7,069 total elective cases, including 3,711 thyroidectomies and 3,358 parathyroidectomies were reviewed.

They found an overall readmission rate of 4.0%, with a rate of 4.1% for patients undergoing thyroidectomy, and 3.8% for those undergoing parathyroidectomy.

Demographic factors significantly associated with a greater likelihood of readmission included diabetes (present in 18.6% of readmitted patients, vs. 12.5% of not readmitted patients; P = .003), severe chronic obstructive pulmonary disease (4.6% vs. 2.0%; P = .002), hemodialysis (11.8% vs. 2.2%; P = .001), and weight loss of more than 10% (1.8% vs. 0.5%; P = .005). Younger and heavier patients were more likely to be readmitted within 30 days than were slightly older and lighter-weight patients.

Complications predict readmission

Postoperative complications associated with readmission included wound complications (5% vs. 0.3%; P less than .001 for all following comparisons, unless noted), respiratory complications 5.4 vs. 0.2%), renal complications (2.1% vs. 0.3%), neurologic complications (0.7% vs. 0.1%; P = .008), and cardiovascular complications (4.6% vs. 0.2%).

In multivariate analysis, factors that were significantly associated with readmission were reoperation within 30 days (P less than .001), American Society of Anesthesiologists physical status class (P = .024), patient functional status (independent vs. partially or fully dependent, P = .007), renal insufficiency (P = .004), and hemodialysis (P = .005).

In contrast, patients who were discharged within 24 hours of surgery were significantly less likely to be readmitted (odds ratio, 0.63; P = .006).

The researchers also found that 63% of patients had a longer than 24-hour stay after surgery – a finding that Dr. Mullen said was surprising – and that patients undergoing surgery for malignant disease were significantly more likely to be readmitted than were patients with benign disease (11% vs. 2.6%, P less than .001). There was no difference in readmission rates of patients treated by general surgeons, compared with those treated by surgeons trained in otolaryngologic procedures.

Dr. Mullen noted that the study was limited by the lack of data on the reasons for each readmission and by a lack of information on many complications that are specific to endocrine surgery.

In the discussion, Dr. Samuel K. Snyder of Texas A & M University in Temple, commented on the lack of study specifics about the reasons for readmission making it hard to draw conclusions about how best to prevent readmissions.

Dr. Mullen responded that because some of the patients had treatable comorbidities such as renal insufficiency, medical augmentation could be a reasonable approach to reducing postoperative complications and risk of readmission.

The authors did not disclose the study funding source. Dr. Mullen and Dr. Snyder reported having no financial disclosures.

BOSTON – Preoperative comorbidities and postoperative complications are the most common reasons that patients are readmitted to a hospital within 30 days of thyroid or parathyroid surgery, but outpatient surgery was associated with a lower likelihood of readmission, investigators have found.

A review of data on more than 7,000 patients who underwent cervical endocrine resections showed that 4% were readmitted within a month of surgery, reported Dr. Matthew G. Mullen, a surgery resident at the University of Virginia Health System in Charlottesville.

"Identifying best practice patterns to avoid major postoperative complications will help reduce hospital readmission rates and improve the quality of patient care," Dr. Mullen said at the annual meeting of the American Association of Endocrine Surgeons.

Previous single-institution studies have shown readmission rates for patients undergoing thyroidectomy of 0.3%-3.9%. A 2010 study of readmission rates among elderly patients undergoing thyroidectomy for thyroid cancer found that 8% required readmission within a month of surgery, Dr. Mullen noted.

To see whether, as they suspected, patients with more medical comorbidities and postoperative complications are more likely to be back in the hospital within 30 days of surgery, the investigators reviewed the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) participant use data file, which includes records on 442,149 elective surgery cases from 315 U.S. hospitals. Data on a total of 7,069 total elective cases, including 3,711 thyroidectomies and 3,358 parathyroidectomies were reviewed.

They found an overall readmission rate of 4.0%, with a rate of 4.1% for patients undergoing thyroidectomy, and 3.8% for those undergoing parathyroidectomy.

Demographic factors significantly associated with a greater likelihood of readmission included diabetes (present in 18.6% of readmitted patients, vs. 12.5% of not readmitted patients; P = .003), severe chronic obstructive pulmonary disease (4.6% vs. 2.0%; P = .002), hemodialysis (11.8% vs. 2.2%; P = .001), and weight loss of more than 10% (1.8% vs. 0.5%; P = .005). Younger and heavier patients were more likely to be readmitted within 30 days than were slightly older and lighter-weight patients.

Complications predict readmission

Postoperative complications associated with readmission included wound complications (5% vs. 0.3%; P less than .001 for all following comparisons, unless noted), respiratory complications 5.4 vs. 0.2%), renal complications (2.1% vs. 0.3%), neurologic complications (0.7% vs. 0.1%; P = .008), and cardiovascular complications (4.6% vs. 0.2%).

In multivariate analysis, factors that were significantly associated with readmission were reoperation within 30 days (P less than .001), American Society of Anesthesiologists physical status class (P = .024), patient functional status (independent vs. partially or fully dependent, P = .007), renal insufficiency (P = .004), and hemodialysis (P = .005).

In contrast, patients who were discharged within 24 hours of surgery were significantly less likely to be readmitted (odds ratio, 0.63; P = .006).

The researchers also found that 63% of patients had a longer than 24-hour stay after surgery – a finding that Dr. Mullen said was surprising – and that patients undergoing surgery for malignant disease were significantly more likely to be readmitted than were patients with benign disease (11% vs. 2.6%, P less than .001). There was no difference in readmission rates of patients treated by general surgeons, compared with those treated by surgeons trained in otolaryngologic procedures.

Dr. Mullen noted that the study was limited by the lack of data on the reasons for each readmission and by a lack of information on many complications that are specific to endocrine surgery.

In the discussion, Dr. Samuel K. Snyder of Texas A & M University in Temple, commented on the lack of study specifics about the reasons for readmission making it hard to draw conclusions about how best to prevent readmissions.

Dr. Mullen responded that because some of the patients had treatable comorbidities such as renal insufficiency, medical augmentation could be a reasonable approach to reducing postoperative complications and risk of readmission.

The authors did not disclose the study funding source. Dr. Mullen and Dr. Snyder reported having no financial disclosures.

BOSTON – Preoperative comorbidities and postoperative complications are the most common reasons that patients are readmitted to a hospital within 30 days of thyroid or parathyroid surgery, but outpatient surgery was associated with a lower likelihood of readmission, investigators have found.

A review of data on more than 7,000 patients who underwent cervical endocrine resections showed that 4% were readmitted within a month of surgery, reported Dr. Matthew G. Mullen, a surgery resident at the University of Virginia Health System in Charlottesville.

"Identifying best practice patterns to avoid major postoperative complications will help reduce hospital readmission rates and improve the quality of patient care," Dr. Mullen said at the annual meeting of the American Association of Endocrine Surgeons.

Previous single-institution studies have shown readmission rates for patients undergoing thyroidectomy of 0.3%-3.9%. A 2010 study of readmission rates among elderly patients undergoing thyroidectomy for thyroid cancer found that 8% required readmission within a month of surgery, Dr. Mullen noted.

To see whether, as they suspected, patients with more medical comorbidities and postoperative complications are more likely to be back in the hospital within 30 days of surgery, the investigators reviewed the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) participant use data file, which includes records on 442,149 elective surgery cases from 315 U.S. hospitals. Data on a total of 7,069 total elective cases, including 3,711 thyroidectomies and 3,358 parathyroidectomies were reviewed.

They found an overall readmission rate of 4.0%, with a rate of 4.1% for patients undergoing thyroidectomy, and 3.8% for those undergoing parathyroidectomy.

Demographic factors significantly associated with a greater likelihood of readmission included diabetes (present in 18.6% of readmitted patients, vs. 12.5% of not readmitted patients; P = .003), severe chronic obstructive pulmonary disease (4.6% vs. 2.0%; P = .002), hemodialysis (11.8% vs. 2.2%; P = .001), and weight loss of more than 10% (1.8% vs. 0.5%; P = .005). Younger and heavier patients were more likely to be readmitted within 30 days than were slightly older and lighter-weight patients.

Complications predict readmission

Postoperative complications associated with readmission included wound complications (5% vs. 0.3%; P less than .001 for all following comparisons, unless noted), respiratory complications 5.4 vs. 0.2%), renal complications (2.1% vs. 0.3%), neurologic complications (0.7% vs. 0.1%; P = .008), and cardiovascular complications (4.6% vs. 0.2%).

In multivariate analysis, factors that were significantly associated with readmission were reoperation within 30 days (P less than .001), American Society of Anesthesiologists physical status class (P = .024), patient functional status (independent vs. partially or fully dependent, P = .007), renal insufficiency (P = .004), and hemodialysis (P = .005).

In contrast, patients who were discharged within 24 hours of surgery were significantly less likely to be readmitted (odds ratio, 0.63; P = .006).

The researchers also found that 63% of patients had a longer than 24-hour stay after surgery – a finding that Dr. Mullen said was surprising – and that patients undergoing surgery for malignant disease were significantly more likely to be readmitted than were patients with benign disease (11% vs. 2.6%, P less than .001). There was no difference in readmission rates of patients treated by general surgeons, compared with those treated by surgeons trained in otolaryngologic procedures.

Dr. Mullen noted that the study was limited by the lack of data on the reasons for each readmission and by a lack of information on many complications that are specific to endocrine surgery.

In the discussion, Dr. Samuel K. Snyder of Texas A & M University in Temple, commented on the lack of study specifics about the reasons for readmission making it hard to draw conclusions about how best to prevent readmissions.

Dr. Mullen responded that because some of the patients had treatable comorbidities such as renal insufficiency, medical augmentation could be a reasonable approach to reducing postoperative complications and risk of readmission.

The authors did not disclose the study funding source. Dr. Mullen and Dr. Snyder reported having no financial disclosures.

BOSTON – Preoperative comorbidities and postoperative complications are the most common reasons that patients are readmitted to a hospital within 30 days of thyroid or parathyroid surgery, but outpatient surgery was associated with a lower likelihood of readmission, investigators have found.

A review of data on more than 7,000 patients who underwent cervical endocrine resections showed that 4% were readmitted within a month of surgery, reported Dr. Matthew G. Mullen, a surgery resident at the University of Virginia Health System in Charlottesville.

"Identifying best practice patterns to avoid major postoperative complications will help reduce hospital readmission rates and improve the quality of patient care," Dr. Mullen said at the annual meeting of the American Association of Endocrine Surgeons.

Previous single-institution studies have shown readmission rates for patients undergoing thyroidectomy of 0.3%-3.9%. A 2010 study of readmission rates among elderly patients undergoing thyroidectomy for thyroid cancer found that 8% required readmission within a month of surgery, Dr. Mullen noted.

To see whether, as they suspected, patients with more medical comorbidities and postoperative complications are more likely to be back in the hospital within 30 days of surgery, the investigators reviewed the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) participant use data file, which includes records on 442,149 elective surgery cases from 315 U.S. hospitals. Data on a total of 7,069 total elective cases, including 3,711 thyroidectomies and 3,358 parathyroidectomies were reviewed.

They found an overall readmission rate of 4.0%, with a rate of 4.1% for patients undergoing thyroidectomy, and 3.8% for those undergoing parathyroidectomy.

Demographic factors significantly associated with a greater likelihood of readmission included diabetes (present in 18.6% of readmitted patients, vs. 12.5% of not readmitted patients; P = .003), severe chronic obstructive pulmonary disease (4.6% vs. 2.0%; P = .002), hemodialysis (11.8% vs. 2.2%; P = .001), and weight loss of more than 10% (1.8% vs. 0.5%; P = .005). Younger and heavier patients were more likely to be readmitted within 30 days than were slightly older and lighter-weight patients.

Complications predict readmission

Postoperative complications associated with readmission included wound complications (5% vs. 0.3%; P less than .001 for all following comparisons, unless noted), respiratory complications 5.4 vs. 0.2%), renal complications (2.1% vs. 0.3%), neurologic complications (0.7% vs. 0.1%; P = .008), and cardiovascular complications (4.6% vs. 0.2%).

In multivariate analysis, factors that were significantly associated with readmission were reoperation within 30 days (P less than .001), American Society of Anesthesiologists physical status class (P = .024), patient functional status (independent vs. partially or fully dependent, P = .007), renal insufficiency (P = .004), and hemodialysis (P = .005).

In contrast, patients who were discharged within 24 hours of surgery were significantly less likely to be readmitted (odds ratio, 0.63; P = .006).

The researchers also found that 63% of patients had a longer than 24-hour stay after surgery – a finding that Dr. Mullen said was surprising – and that patients undergoing surgery for malignant disease were significantly more likely to be readmitted than were patients with benign disease (11% vs. 2.6%, P less than .001). There was no difference in readmission rates of patients treated by general surgeons, compared with those treated by surgeons trained in otolaryngologic procedures.

Dr. Mullen noted that the study was limited by the lack of data on the reasons for each readmission and by a lack of information on many complications that are specific to endocrine surgery.

In the discussion, Dr. Samuel K. Snyder of Texas A & M University in Temple, commented on the lack of study specifics about the reasons for readmission making it hard to draw conclusions about how best to prevent readmissions.

Dr. Mullen responded that because some of the patients had treatable comorbidities such as renal insufficiency, medical augmentation could be a reasonable approach to reducing postoperative complications and risk of readmission.

The authors did not disclose the study funding source. Dr. Mullen and Dr. Snyder reported having no financial disclosures.

NEW YORK – The likelihood that patients with major mood disorders will attempt or complete suicide appears to be related to the amount of time they spend in high-risk states of illness, results of longitudinal studies suggest.

"Among mood disorder patients, in any setting, there is a very strong association between suicidal acts and mood state," said Dr. Erkki T. Isometsä, professor of psychiatry at the University of Helsinki.

"Time spent in high-risk illness states is a major determinant of overall risk. Thus, for prevention of suicidal acts, reducing time in high-risk illness states is essential," he said at the American Psychiatric Association annual meeting.

Neil Osterweil/Frontline Medical News

Providing effective acute therapies and maintenance-phase treatment and improving continuity of care has the potential to significantly decrease suicidal acts, Dr. Isometsä said.

He noted that half of all suicides are committed by people who suffer from major mood disorders such as depression and bipolar disorder. A recently published meta-analysis and systematic review found that factors significantly associated with suicide were male sex (odds ratio, 1.76); a family history of psychiatric disorder (OR, 1.41); previous suicide attempt (OR, 4.84); more severe depression (OR, 2.20); hopelessness (OR, 2.20); and comorbid disorders, including anxiety (OR, 1.59) and substance misuse (OR, 2.17) (J. Affect. Disord. 2013;147:17-28).

Dr. Isometsä pointed to an International Society for Bipolar Disorders (ISBD) task force on suicide, whose members identified risk variables associated with suicide attempts and suicide deaths.

Suicide attempts were more likely in patients with bipolar disorder who had depressive polarity of their first, current, or most recent illness episode; comorbid cluster/borderline personality disorder; any comorbid anxiety or substance use disorder; history of suicide in a first-degree relative; female sex; and younger age of illness at onset.

However, only suicide of a first-degree relative and male sex were significantly associated with suicide deaths.

Longitudinal studies

Dr. Isometsä was the lead investigator for two longitudinal studies of Finnish patients with mood disorders: the Vantaa Primary Care Depression Study and the Jorvi Bipolar Study. Both studies looked at the incidence of suicide attempts over time across variable mood states.

In the depression study, the investigators compared the incidence of suicide attempts among depressed patients during major depressive episodes, partial remissions, and full remissions over 5 years of follow-up and found that 78% of the attempts (adjusted population attributable fraction [PAF]) occurred during major depressive episodes.

Factors significantly associated with suicide attempts were a prior attempt (OR, 4.39), partial vs. full remission (OR, 4.20), and major depressive episode (OR, 7.74).

Protective factors included age (OR, 0.94), married or cohabiting (OR, 0.43), intermediate social support (OR, 0.36), and high social support (OR, 0.28).

In the Jorvi Bipolar Study, which looked at patients with both bipolar disorders I and II, the incidence was of suicide attempts was 37 times higher when patients were in combined mixed and depressive mixed states and 18-fold higher during major depressive phases, compared with other illness states. In this study, the PAF for time spent in high-risk illness phase was 86%.

In each study, suicidal acts during mood episodes also was more likely among patients who had hopelessness, a history of abuse in childhood, poor social support, concurrent substance use, cluster B personality disorders, and those with impulsive-aggressive traits.

But of all of the associated factors, time spent in high-risk phases of illness appeared to be the predominant, modifiable driver of suicidal acts, Dr. Isometsä concluded.

The Vantaa and Jorvi studies were supported by the National Institute for Health and Welfare, Finland. Dr. Isometsä reported having no conflicts of interest.

NEW YORK – The likelihood that patients with major mood disorders will attempt or complete suicide appears to be related to the amount of time they spend in high-risk states of illness, results of longitudinal studies suggest.

"Among mood disorder patients, in any setting, there is a very strong association between suicidal acts and mood state," said Dr. Erkki T. Isometsä, professor of psychiatry at the University of Helsinki.

"Time spent in high-risk illness states is a major determinant of overall risk. Thus, for prevention of suicidal acts, reducing time in high-risk illness states is essential," he said at the American Psychiatric Association annual meeting.

Neil Osterweil/Frontline Medical News

Providing effective acute therapies and maintenance-phase treatment and improving continuity of care has the potential to significantly decrease suicidal acts, Dr. Isometsä said.

He noted that half of all suicides are committed by people who suffer from major mood disorders such as depression and bipolar disorder. A recently published meta-analysis and systematic review found that factors significantly associated with suicide were male sex (odds ratio, 1.76); a family history of psychiatric disorder (OR, 1.41); previous suicide attempt (OR, 4.84); more severe depression (OR, 2.20); hopelessness (OR, 2.20); and comorbid disorders, including anxiety (OR, 1.59) and substance misuse (OR, 2.17) (J. Affect. Disord. 2013;147:17-28).

Dr. Isometsä pointed to an International Society for Bipolar Disorders (ISBD) task force on suicide, whose members identified risk variables associated with suicide attempts and suicide deaths.

Suicide attempts were more likely in patients with bipolar disorder who had depressive polarity of their first, current, or most recent illness episode; comorbid cluster/borderline personality disorder; any comorbid anxiety or substance use disorder; history of suicide in a first-degree relative; female sex; and younger age of illness at onset.

However, only suicide of a first-degree relative and male sex were significantly associated with suicide deaths.

Longitudinal studies

Dr. Isometsä was the lead investigator for two longitudinal studies of Finnish patients with mood disorders: the Vantaa Primary Care Depression Study and the Jorvi Bipolar Study. Both studies looked at the incidence of suicide attempts over time across variable mood states.

In the depression study, the investigators compared the incidence of suicide attempts among depressed patients during major depressive episodes, partial remissions, and full remissions over 5 years of follow-up and found that 78% of the attempts (adjusted population attributable fraction [PAF]) occurred during major depressive episodes.

Factors significantly associated with suicide attempts were a prior attempt (OR, 4.39), partial vs. full remission (OR, 4.20), and major depressive episode (OR, 7.74).

Protective factors included age (OR, 0.94), married or cohabiting (OR, 0.43), intermediate social support (OR, 0.36), and high social support (OR, 0.28).

In the Jorvi Bipolar Study, which looked at patients with both bipolar disorders I and II, the incidence was of suicide attempts was 37 times higher when patients were in combined mixed and depressive mixed states and 18-fold higher during major depressive phases, compared with other illness states. In this study, the PAF for time spent in high-risk illness phase was 86%.

In each study, suicidal acts during mood episodes also was more likely among patients who had hopelessness, a history of abuse in childhood, poor social support, concurrent substance use, cluster B personality disorders, and those with impulsive-aggressive traits.

But of all of the associated factors, time spent in high-risk phases of illness appeared to be the predominant, modifiable driver of suicidal acts, Dr. Isometsä concluded.

The Vantaa and Jorvi studies were supported by the National Institute for Health and Welfare, Finland. Dr. Isometsä reported having no conflicts of interest.

NEW YORK – The likelihood that patients with major mood disorders will attempt or complete suicide appears to be related to the amount of time they spend in high-risk states of illness, results of longitudinal studies suggest.

"Among mood disorder patients, in any setting, there is a very strong association between suicidal acts and mood state," said Dr. Erkki T. Isometsä, professor of psychiatry at the University of Helsinki.

"Time spent in high-risk illness states is a major determinant of overall risk. Thus, for prevention of suicidal acts, reducing time in high-risk illness states is essential," he said at the American Psychiatric Association annual meeting.

Neil Osterweil/Frontline Medical News

Providing effective acute therapies and maintenance-phase treatment and improving continuity of care has the potential to significantly decrease suicidal acts, Dr. Isometsä said.

He noted that half of all suicides are committed by people who suffer from major mood disorders such as depression and bipolar disorder. A recently published meta-analysis and systematic review found that factors significantly associated with suicide were male sex (odds ratio, 1.76); a family history of psychiatric disorder (OR, 1.41); previous suicide attempt (OR, 4.84); more severe depression (OR, 2.20); hopelessness (OR, 2.20); and comorbid disorders, including anxiety (OR, 1.59) and substance misuse (OR, 2.17) (J. Affect. Disord. 2013;147:17-28).

Dr. Isometsä pointed to an International Society for Bipolar Disorders (ISBD) task force on suicide, whose members identified risk variables associated with suicide attempts and suicide deaths.

Suicide attempts were more likely in patients with bipolar disorder who had depressive polarity of their first, current, or most recent illness episode; comorbid cluster/borderline personality disorder; any comorbid anxiety or substance use disorder; history of suicide in a first-degree relative; female sex; and younger age of illness at onset.

However, only suicide of a first-degree relative and male sex were significantly associated with suicide deaths.

Longitudinal studies

Dr. Isometsä was the lead investigator for two longitudinal studies of Finnish patients with mood disorders: the Vantaa Primary Care Depression Study and the Jorvi Bipolar Study. Both studies looked at the incidence of suicide attempts over time across variable mood states.

In the depression study, the investigators compared the incidence of suicide attempts among depressed patients during major depressive episodes, partial remissions, and full remissions over 5 years of follow-up and found that 78% of the attempts (adjusted population attributable fraction [PAF]) occurred during major depressive episodes.

Factors significantly associated with suicide attempts were a prior attempt (OR, 4.39), partial vs. full remission (OR, 4.20), and major depressive episode (OR, 7.74).

Protective factors included age (OR, 0.94), married or cohabiting (OR, 0.43), intermediate social support (OR, 0.36), and high social support (OR, 0.28).

In the Jorvi Bipolar Study, which looked at patients with both bipolar disorders I and II, the incidence was of suicide attempts was 37 times higher when patients were in combined mixed and depressive mixed states and 18-fold higher during major depressive phases, compared with other illness states. In this study, the PAF for time spent in high-risk illness phase was 86%.

In each study, suicidal acts during mood episodes also was more likely among patients who had hopelessness, a history of abuse in childhood, poor social support, concurrent substance use, cluster B personality disorders, and those with impulsive-aggressive traits.

But of all of the associated factors, time spent in high-risk phases of illness appeared to be the predominant, modifiable driver of suicidal acts, Dr. Isometsä concluded.

The Vantaa and Jorvi studies were supported by the National Institute for Health and Welfare, Finland. Dr. Isometsä reported having no conflicts of interest.

NEW YORK – A combination of four readily available clinical and psychosocial tests can predict whether patients are at risk for converting to psychosis with fair to good positive predictive value, an investigator asserts.

Measures of thought content, suspiciousness, and subscales of the Brief Assessment of Cognition in Schizophrenia instrument, as well as total life events, can predict with fairly good sensitivity and specificity which patients will progress to psychosis, said Tyrone D. Cannon, Ph.D., professor of psychology and psychiatry at Yale University in New Haven, Conn.

"The foundation of any effective prevention program has to be begin with the goal of prediction; we have to find the people most at risk. And then another pillar of prevention is understanding something about the underlying mechanisms of illness," he said at the American Psychiatric Association annual meeting.

Neil Osterweil/Frontline Medical News

The clinical high-risk paradigm (CHR) is based on the establishment of CHR criteria that can capture the population at risk of imminent onset of psychosis.

A recent systematic review risk of CHR research (JAMA Psychiatry 2013;70:107-20) found that among high-risk patients, rates of conversion to psychosis were about 15% by 1 year of follow-up and 30% by 2 years. Of those who convert to psychosis, about 80% develop a schizophrenia spectrum disorder, and about 20% develop mood or atypical psychoses.

A second study (Schizophr. Bull. 2012;38:1225-33) showed that of nonconverters, one-third recover symptomatically by 2 years, an additional third recover functionally, and another third recover both symptomatically and functionally.

Therefore, a good rule of thumb is that among CHR populations, about one-third will remit, one-third will convert to psychosis, and one-third will remain in a CHR state, Dr. Cannon said. Of the latter group, some might convert to schizophrenia or psychosis, and some might develop schizotypal disorders.

Currently available multivariate algorithms that involve specific combinations of symptoms and demographic factors generally have high positive predictive values and specificity but tend to have low sensitivity, and the accepted diagnostic profiles vary widely across different studies, he said.

Dr. Cannon and colleagues in the NAPLS (North American Prodrome Longitudinal Study) consortium have studied clinical predictors of psychosis in 360 of the 750 planned CHR patients recruited. Of this group, 60 converted to psychosis within 2 years, and the remaining nonconverters were followed for the same period.

The investigators examined the receiver operating characteristic (ROC) curves for predictive models for which there were 10 or more converters per predictor. Using this method, a value of 1 indicates a perfect test result, and a value of .5 area-under-the-curve (AUC) is a poor or failed result.

"There are a number of predictors that have emerged from the prior literature that in this new sample are indeed confirmed as very robustly predictive. The single best one is the rated function of what we call P1 and P2, which are the symptoms of unusual thought content and suspiciousness. Higher levels of those, still at a prepsychotic level, but at a higher, prodromal level of activity, predicts psychosis with pretty high accuracy on their own," Dr. Cannon said.

For P1 and P2, the AUC was 0.668 and was significantly predictive (P less than .0001). Other significant markers included the digital sequencing subscale of the Brief Assessment of Cognition in Schizophrenia (BACS) (AUC 0.614; P = .0018) and the Hopkins Verbal Learning Test (AUC 0.630; P = .0005). A less robust but still significant predictor was the total number of life events (AUC 0.579; P = .0495).

Combining the four markers yielded an AUC of 0.74, with a sensitivity of 70% and specificity of 73%. The positive predictive value was relatively low, at 46%, but the negative predictive value of the combination was fairly good, at 88%, Dr. Cannon pointed out.

The NAPLS investigators also are investigating whether specific biomarkers such as cortisol levels and change in prefrontal gray matter volume and event-related potential can identify patients who will convert to schizophrenia or other psychotic states.

The NAPLS consortium is supported by the National Institute of Mental Health. Dr. Cannon disclosed that he is a consultant to the Los Angeles County Department of Mental Health on early detection and prevention services.

NEW YORK – A combination of four readily available clinical and psychosocial tests can predict whether patients are at risk for converting to psychosis with fair to good positive predictive value, an investigator asserts.

Measures of thought content, suspiciousness, and subscales of the Brief Assessment of Cognition in Schizophrenia instrument, as well as total life events, can predict with fairly good sensitivity and specificity which patients will progress to psychosis, said Tyrone D. Cannon, Ph.D., professor of psychology and psychiatry at Yale University in New Haven, Conn.

"The foundation of any effective prevention program has to be begin with the goal of prediction; we have to find the people most at risk. And then another pillar of prevention is understanding something about the underlying mechanisms of illness," he said at the American Psychiatric Association annual meeting.

Neil Osterweil/Frontline Medical News

The clinical high-risk paradigm (CHR) is based on the establishment of CHR criteria that can capture the population at risk of imminent onset of psychosis.

A recent systematic review risk of CHR research (JAMA Psychiatry 2013;70:107-20) found that among high-risk patients, rates of conversion to psychosis were about 15% by 1 year of follow-up and 30% by 2 years. Of those who convert to psychosis, about 80% develop a schizophrenia spectrum disorder, and about 20% develop mood or atypical psychoses.

A second study (Schizophr. Bull. 2012;38:1225-33) showed that of nonconverters, one-third recover symptomatically by 2 years, an additional third recover functionally, and another third recover both symptomatically and functionally.

Therefore, a good rule of thumb is that among CHR populations, about one-third will remit, one-third will convert to psychosis, and one-third will remain in a CHR state, Dr. Cannon said. Of the latter group, some might convert to schizophrenia or psychosis, and some might develop schizotypal disorders.

Currently available multivariate algorithms that involve specific combinations of symptoms and demographic factors generally have high positive predictive values and specificity but tend to have low sensitivity, and the accepted diagnostic profiles vary widely across different studies, he said.

Dr. Cannon and colleagues in the NAPLS (North American Prodrome Longitudinal Study) consortium have studied clinical predictors of psychosis in 360 of the 750 planned CHR patients recruited. Of this group, 60 converted to psychosis within 2 years, and the remaining nonconverters were followed for the same period.

The investigators examined the receiver operating characteristic (ROC) curves for predictive models for which there were 10 or more converters per predictor. Using this method, a value of 1 indicates a perfect test result, and a value of .5 area-under-the-curve (AUC) is a poor or failed result.

"There are a number of predictors that have emerged from the prior literature that in this new sample are indeed confirmed as very robustly predictive. The single best one is the rated function of what we call P1 and P2, which are the symptoms of unusual thought content and suspiciousness. Higher levels of those, still at a prepsychotic level, but at a higher, prodromal level of activity, predicts psychosis with pretty high accuracy on their own," Dr. Cannon said.

For P1 and P2, the AUC was 0.668 and was significantly predictive (P less than .0001). Other significant markers included the digital sequencing subscale of the Brief Assessment of Cognition in Schizophrenia (BACS) (AUC 0.614; P = .0018) and the Hopkins Verbal Learning Test (AUC 0.630; P = .0005). A less robust but still significant predictor was the total number of life events (AUC 0.579; P = .0495).

Combining the four markers yielded an AUC of 0.74, with a sensitivity of 70% and specificity of 73%. The positive predictive value was relatively low, at 46%, but the negative predictive value of the combination was fairly good, at 88%, Dr. Cannon pointed out.

The NAPLS investigators also are investigating whether specific biomarkers such as cortisol levels and change in prefrontal gray matter volume and event-related potential can identify patients who will convert to schizophrenia or other psychotic states.

The NAPLS consortium is supported by the National Institute of Mental Health. Dr. Cannon disclosed that he is a consultant to the Los Angeles County Department of Mental Health on early detection and prevention services.

NEW YORK – A combination of four readily available clinical and psychosocial tests can predict whether patients are at risk for converting to psychosis with fair to good positive predictive value, an investigator asserts.

Measures of thought content, suspiciousness, and subscales of the Brief Assessment of Cognition in Schizophrenia instrument, as well as total life events, can predict with fairly good sensitivity and specificity which patients will progress to psychosis, said Tyrone D. Cannon, Ph.D., professor of psychology and psychiatry at Yale University in New Haven, Conn.

"The foundation of any effective prevention program has to be begin with the goal of prediction; we have to find the people most at risk. And then another pillar of prevention is understanding something about the underlying mechanisms of illness," he said at the American Psychiatric Association annual meeting.

Neil Osterweil/Frontline Medical News

The clinical high-risk paradigm (CHR) is based on the establishment of CHR criteria that can capture the population at risk of imminent onset of psychosis.

A recent systematic review risk of CHR research (JAMA Psychiatry 2013;70:107-20) found that among high-risk patients, rates of conversion to psychosis were about 15% by 1 year of follow-up and 30% by 2 years. Of those who convert to psychosis, about 80% develop a schizophrenia spectrum disorder, and about 20% develop mood or atypical psychoses.

A second study (Schizophr. Bull. 2012;38:1225-33) showed that of nonconverters, one-third recover symptomatically by 2 years, an additional third recover functionally, and another third recover both symptomatically and functionally.

Therefore, a good rule of thumb is that among CHR populations, about one-third will remit, one-third will convert to psychosis, and one-third will remain in a CHR state, Dr. Cannon said. Of the latter group, some might convert to schizophrenia or psychosis, and some might develop schizotypal disorders.

Currently available multivariate algorithms that involve specific combinations of symptoms and demographic factors generally have high positive predictive values and specificity but tend to have low sensitivity, and the accepted diagnostic profiles vary widely across different studies, he said.

Dr. Cannon and colleagues in the NAPLS (North American Prodrome Longitudinal Study) consortium have studied clinical predictors of psychosis in 360 of the 750 planned CHR patients recruited. Of this group, 60 converted to psychosis within 2 years, and the remaining nonconverters were followed for the same period.

The investigators examined the receiver operating characteristic (ROC) curves for predictive models for which there were 10 or more converters per predictor. Using this method, a value of 1 indicates a perfect test result, and a value of .5 area-under-the-curve (AUC) is a poor or failed result.

"There are a number of predictors that have emerged from the prior literature that in this new sample are indeed confirmed as very robustly predictive. The single best one is the rated function of what we call P1 and P2, which are the symptoms of unusual thought content and suspiciousness. Higher levels of those, still at a prepsychotic level, but at a higher, prodromal level of activity, predicts psychosis with pretty high accuracy on their own," Dr. Cannon said.

For P1 and P2, the AUC was 0.668 and was significantly predictive (P less than .0001). Other significant markers included the digital sequencing subscale of the Brief Assessment of Cognition in Schizophrenia (BACS) (AUC 0.614; P = .0018) and the Hopkins Verbal Learning Test (AUC 0.630; P = .0005). A less robust but still significant predictor was the total number of life events (AUC 0.579; P = .0495).

Combining the four markers yielded an AUC of 0.74, with a sensitivity of 70% and specificity of 73%. The positive predictive value was relatively low, at 46%, but the negative predictive value of the combination was fairly good, at 88%, Dr. Cannon pointed out.

The NAPLS investigators also are investigating whether specific biomarkers such as cortisol levels and change in prefrontal gray matter volume and event-related potential can identify patients who will convert to schizophrenia or other psychotic states.

The NAPLS consortium is supported by the National Institute of Mental Health. Dr. Cannon disclosed that he is a consultant to the Los Angeles County Department of Mental Health on early detection and prevention services.

Annual low-dose CT screening of patients at high risk for lung cancer is likely to significantly increase detection of early cancers, but that screening will come at a price, investigators say.

A model that simulates screening of Medicare patients based on recent recommendations from the U.S. Preventive Services Task Force (USPSTF) predicts that an additional 54,000 or so cases of lung cancer would be detected over 5 years, and that most of the cases would be early-stage disease and presumably more easily treated, said Joshua A. Roth, Ph.D., a postdoctoral research fellow at the Fred Hutchinson Cancer Research Center, Seattle.

The model also calculates, however, that the total 5-year Medicare expenditure for a low-dose CT, a diagnostic workup, and cancer care would be $9.3 billion.

Depending on how heavily screening is used, total estimated 5-year costs could range from a low of $5.9 billion (adding $1.90 to monthly premiums) to a high of $12.7 billion ($4.10 extra per month).

"We projected over a 5-year time horizon [that] implementing low-dose CT lung cancer screening in Medicare would result in more lung cancers detected, a shift toward earlier stage at diagnosis, and increased expenditure, particularly on CT scans themselves," Dr. Roth said at a media briefing highlighting research to be presented at the annual meeting of the American Society of Clinical Oncology in Chicago, from May 30 through June 3.

"If screening is covered, it's important for Medicare and health care systems to plan for increased demand for CT imaging and early-stage treatments, for example, thoracic surgery and radiation therapy. Additionally, Medicare should plan for increased expenditure in the budgeting process, as these expenditure increases will need to be funded by either increased premiums or by offsetting other costs," he added.

In December 2013, the USPSTF published a statement recommending annual low-dose CT lung cancer screening for patients from the ages of 55 to 80 years with 30 or more pack-years of smoking history who currently smoke or have quit within the past 15 years. Medicare is scheduled to post a draft decision in November 2014 on whether it will cover the cost of screening under the provision of the Affordable Care Act. Dr. Roth noted that at a recent Medicare coverage advisory meeting, the panelists voted against recommending coverage for screening due to uncertainties about benefits outside of clinical trials.

The authors created their model to mirror the Medicare enrollment and age distribution for 2013. They plugged in lung cancer detection rates and stage at diagnosis using data from the National Lung Cancer Screening Trial, and data on costs of low-dose CT screening and follow-up, confirmatory bronchoscopy and biopsy, as well as stage-specific costs of lung cancer therapy, including the costs associated with end-stage disease.

They looked at three possible scenarios: expected use (based on mammography screening experience), in which about half of all patients offered screening every year actually receive it; low use (25% per year); and high use (75% per year).

They found that if screening is used as expected, it would result in 11.2 million more scans and 54,000 incident cases of lung cancer (most stage 1) over 5 years, compared with no screening. The estimated costs would total $9.3 billion, composed of $5.6 billion more in imaging expenditures, $1.1 billion in diagnostic workups, and $2.6 billion in additional cancer care expenditures.

This increase would translate into a bump in monthly Medicare premiums of $3 per enrollee.  By way of comparison, Dr. Roth pointed to a 2012 study in which the authors performed an actuarial analysis showing that offering lung cancer screening as an insurance benefit for the general population would cost about $1 per member per month in 2012 dollars, and that the cost per life-year saved would be below $19,000, which compares favorably with the cost of screening for colorectal, cervical, and breast cancers. He noted, however, that the findings of that study applied to all insured patients, and may not be applicable to the Medicare-only population.

 The authors estimated that screening under the expected-use scenario would double the proportion of early-stage cancers detected from the current 15% to 32%, and reduce the proportion of cancers detected in more advanced stages from the current 57% to 40%.

The investigators plan to look at the availability of imaging equipment and trained personnel to estimate how they might be affected by immediate or gradual implementation of the screening recommendations.

Dr. Peter Yu, president-elect of ASCO and a medical oncologist at Palo Alto Medical Foundation in Sunnyvale, Calif., noted that ASCO guidelines support the USPSTF recommendations.

He cautioned, however, that the study provides a forecast of cost but does not reflect real-world expenditures.

"This is a model; this is not actual data," he cautioned.

The study was supported by Genentech. Dr. Roth and Dr. Yu reported having no financial disclosures.

Annual low-dose CT screening of patients at high risk for lung cancer is likely to significantly increase detection of early cancers, but that screening will come at a price, investigators say.

A model that simulates screening of Medicare patients based on recent recommendations from the U.S. Preventive Services Task Force (USPSTF) predicts that an additional 54,000 or so cases of lung cancer would be detected over 5 years, and that most of the cases would be early-stage disease and presumably more easily treated, said Joshua A. Roth, Ph.D., a postdoctoral research fellow at the Fred Hutchinson Cancer Research Center, Seattle.

The model also calculates, however, that the total 5-year Medicare expenditure for a low-dose CT, a diagnostic workup, and cancer care would be $9.3 billion.

Depending on how heavily screening is used, total estimated 5-year costs could range from a low of $5.9 billion (adding $1.90 to monthly premiums) to a high of $12.7 billion ($4.10 extra per month).

"We projected over a 5-year time horizon [that] implementing low-dose CT lung cancer screening in Medicare would result in more lung cancers detected, a shift toward earlier stage at diagnosis, and increased expenditure, particularly on CT scans themselves," Dr. Roth said at a media briefing highlighting research to be presented at the annual meeting of the American Society of Clinical Oncology in Chicago, from May 30 through June 3.

"If screening is covered, it's important for Medicare and health care systems to plan for increased demand for CT imaging and early-stage treatments, for example, thoracic surgery and radiation therapy. Additionally, Medicare should plan for increased expenditure in the budgeting process, as these expenditure increases will need to be funded by either increased premiums or by offsetting other costs," he added.

In December 2013, the USPSTF published a statement recommending annual low-dose CT lung cancer screening for patients from the ages of 55 to 80 years with 30 or more pack-years of smoking history who currently smoke or have quit within the past 15 years. Medicare is scheduled to post a draft decision in November 2014 on whether it will cover the cost of screening under the provision of the Affordable Care Act. Dr. Roth noted that at a recent Medicare coverage advisory meeting, the panelists voted against recommending coverage for screening due to uncertainties about benefits outside of clinical trials.

The authors created their model to mirror the Medicare enrollment and age distribution for 2013. They plugged in lung cancer detection rates and stage at diagnosis using data from the National Lung Cancer Screening Trial, and data on costs of low-dose CT screening and follow-up, confirmatory bronchoscopy and biopsy, as well as stage-specific costs of lung cancer therapy, including the costs associated with end-stage disease.

They looked at three possible scenarios: expected use (based on mammography screening experience), in which about half of all patients offered screening every year actually receive it; low use (25% per year); and high use (75% per year).

They found that if screening is used as expected, it would result in 11.2 million more scans and 54,000 incident cases of lung cancer (most stage 1) over 5 years, compared with no screening. The estimated costs would total $9.3 billion, composed of $5.6 billion more in imaging expenditures, $1.1 billion in diagnostic workups, and $2.6 billion in additional cancer care expenditures.

This increase would translate into a bump in monthly Medicare premiums of $3 per enrollee.  By way of comparison, Dr. Roth pointed to a 2012 study in which the authors performed an actuarial analysis showing that offering lung cancer screening as an insurance benefit for the general population would cost about $1 per member per month in 2012 dollars, and that the cost per life-year saved would be below $19,000, which compares favorably with the cost of screening for colorectal, cervical, and breast cancers. He noted, however, that the findings of that study applied to all insured patients, and may not be applicable to the Medicare-only population.

 The authors estimated that screening under the expected-use scenario would double the proportion of early-stage cancers detected from the current 15% to 32%, and reduce the proportion of cancers detected in more advanced stages from the current 57% to 40%.

The investigators plan to look at the availability of imaging equipment and trained personnel to estimate how they might be affected by immediate or gradual implementation of the screening recommendations.

Dr. Peter Yu, president-elect of ASCO and a medical oncologist at Palo Alto Medical Foundation in Sunnyvale, Calif., noted that ASCO guidelines support the USPSTF recommendations.

He cautioned, however, that the study provides a forecast of cost but does not reflect real-world expenditures.

"This is a model; this is not actual data," he cautioned.

The study was supported by Genentech. Dr. Roth and Dr. Yu reported having no financial disclosures.

Annual low-dose CT screening of patients at high risk for lung cancer is likely to significantly increase detection of early cancers, but that screening will come at a price, investigators say.

A model that simulates screening of Medicare patients based on recent recommendations from the U.S. Preventive Services Task Force (USPSTF) predicts that an additional 54,000 or so cases of lung cancer would be detected over 5 years, and that most of the cases would be early-stage disease and presumably more easily treated, said Joshua A. Roth, Ph.D., a postdoctoral research fellow at the Fred Hutchinson Cancer Research Center, Seattle.

The model also calculates, however, that the total 5-year Medicare expenditure for a low-dose CT, a diagnostic workup, and cancer care would be $9.3 billion.

Depending on how heavily screening is used, total estimated 5-year costs could range from a low of $5.9 billion (adding $1.90 to monthly premiums) to a high of $12.7 billion ($4.10 extra per month).

"We projected over a 5-year time horizon [that] implementing low-dose CT lung cancer screening in Medicare would result in more lung cancers detected, a shift toward earlier stage at diagnosis, and increased expenditure, particularly on CT scans themselves," Dr. Roth said at a media briefing highlighting research to be presented at the annual meeting of the American Society of Clinical Oncology in Chicago, from May 30 through June 3.

"If screening is covered, it's important for Medicare and health care systems to plan for increased demand for CT imaging and early-stage treatments, for example, thoracic surgery and radiation therapy. Additionally, Medicare should plan for increased expenditure in the budgeting process, as these expenditure increases will need to be funded by either increased premiums or by offsetting other costs," he added.

In December 2013, the USPSTF published a statement recommending annual low-dose CT lung cancer screening for patients from the ages of 55 to 80 years with 30 or more pack-years of smoking history who currently smoke or have quit within the past 15 years. Medicare is scheduled to post a draft decision in November 2014 on whether it will cover the cost of screening under the provision of the Affordable Care Act. Dr. Roth noted that at a recent Medicare coverage advisory meeting, the panelists voted against recommending coverage for screening due to uncertainties about benefits outside of clinical trials.

The authors created their model to mirror the Medicare enrollment and age distribution for 2013. They plugged in lung cancer detection rates and stage at diagnosis using data from the National Lung Cancer Screening Trial, and data on costs of low-dose CT screening and follow-up, confirmatory bronchoscopy and biopsy, as well as stage-specific costs of lung cancer therapy, including the costs associated with end-stage disease.

They looked at three possible scenarios: expected use (based on mammography screening experience), in which about half of all patients offered screening every year actually receive it; low use (25% per year); and high use (75% per year).

They found that if screening is used as expected, it would result in 11.2 million more scans and 54,000 incident cases of lung cancer (most stage 1) over 5 years, compared with no screening. The estimated costs would total $9.3 billion, composed of $5.6 billion more in imaging expenditures, $1.1 billion in diagnostic workups, and $2.6 billion in additional cancer care expenditures.

This increase would translate into a bump in monthly Medicare premiums of $3 per enrollee.  By way of comparison, Dr. Roth pointed to a 2012 study in which the authors performed an actuarial analysis showing that offering lung cancer screening as an insurance benefit for the general population would cost about $1 per member per month in 2012 dollars, and that the cost per life-year saved would be below $19,000, which compares favorably with the cost of screening for colorectal, cervical, and breast cancers. He noted, however, that the findings of that study applied to all insured patients, and may not be applicable to the Medicare-only population.

 The authors estimated that screening under the expected-use scenario would double the proportion of early-stage cancers detected from the current 15% to 32%, and reduce the proportion of cancers detected in more advanced stages from the current 57% to 40%.

The investigators plan to look at the availability of imaging equipment and trained personnel to estimate how they might be affected by immediate or gradual implementation of the screening recommendations.

Dr. Peter Yu, president-elect of ASCO and a medical oncologist at Palo Alto Medical Foundation in Sunnyvale, Calif., noted that ASCO guidelines support the USPSTF recommendations.

He cautioned, however, that the study provides a forecast of cost but does not reflect real-world expenditures.

"This is a model; this is not actual data," he cautioned.

The study was supported by Genentech. Dr. Roth and Dr. Yu reported having no financial disclosures.

Obesity appears to increase the risk of breast cancer–related deaths by about one-third in premenopausal but, surprisingly, not postmenopausal women with estrogen receptor–positive disease, investigators report.

An analysis of pooled data on 80,000 patients enrolled in 70 clinical trials showed that among 60,000 patients with estrogen receptor (ER)-positive disease, body mass index (BMI) was associated with risk for breast cancer mortality in both pre- and perimenopausal women.

 But after adjustment for patient factors and tumor characteristics, the association remained significant only for premenopausal women with ER-positive tumors, who had a 34% higher risk of dying from breast cancer, said Dr. Hongchao Pan, on behalf of colleagues in the Early Breast Cancer Trialists’ Collaborative Group.

“To our surprise, we found little independent adverse effects of obesity in the 40,000 postmenopausal women with ER-positive disease,” Dr. Pan said at a media briefing highlighting research to be presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, from May 30 through June 3.

There was also no apparent effect among women of any age with ER-negative tumors.

The findings suggest that the mechanisms by which obesity contributes to breast cancer prognosis are still unclear, Dr. Pan said.

Dr. Peter Yu, president-elect of ASCO and a medical oncologist at Palo Alto Medical Foundation in Sunnyvale, Calif., noted that the study looked only at the role of obesity in breast cancer prognosis, and did not consider its potential contributions to oncogenesis.

“The bottom line, of course, remains that obesity is overall a negative prognostic feature, and something that we will need to address at a societal level,” he said.

Dr. Yu comoderated the briefing, but was not involved in the study.

The other moderator, Dr. Clifford Hudis, president of ASCO and chief of the breast cancer service at Memorial Sloan Kettering Cancer Center, New York, commented that both overweight and obesity are known to contribute to risk for postmenopausal, ER-positive breast cancer.

Obesity is associated with inflammation of white adipose tissue, including adipose tissue of the breast, through up-regulation of inflammatory mediators such as interleukin-6 and prostaglandin. The mediators activate the cytochrome P19 gene, which encodes for the aromatase enzyme, Dr. Hudis explained.

“People who have this low-grade inflammation will have increased aromatase activity, increased local production of estrogen, and that provides an explanation for the paradox of elevated ER-positive breast cancer with obesity after menopause, when the ovaries have stopped higher production of estrogen,” he said.

“I am surprised that the effect was less clear in the postmenopausal than the premenopausal patients [in this study], so I think this is something we’re going to have to explore further,” he said.

Dr. Pan and colleagues collected data on 80,000 individual patients in 70 early breast cancer trials, including information on BMI, ER status, menopausal status, recurrence, and cause of death,

In Cox regression analysis adjusted for age, surgery type, trial treatment, HER-2 receptor status, nodal status, tumor grade, and diameter, they looked at obesity as an independent factor associated with breast cancer mortality.

They found that among premenopausal women, obesity was associated with a relative risk for death of 1.34 (95% confidence interval, 1.22-1.47). In contrast, there was only a weak, nonsignificant effect in postmenopausal, ER-positive women (RR, 1.06; CI, 0.99-1.14), and no effect whatsoever in women with ER-negative tumors (RR, 1.00; CI, 0.93-1.08).

A comparison of obese women (BMI, 30 kg/m² or greater) with those of normal weight (BMI, 20-25) showed 10-year death rates of 21.5% and 16.6%, respectively. The absolute difference at 10 years was 5%, Dr. Pan said.

The study was funded by Cancer Research UK, the Medical Research Council, and the British Heart Foundation. Dr. Pan, Dr. Yu, and Dr. Hudis reported having no relevant financial disclosures.

Obesity appears to increase the risk of breast cancer–related deaths by about one-third in premenopausal but, surprisingly, not postmenopausal women with estrogen receptor–positive disease, investigators report.

An analysis of pooled data on 80,000 patients enrolled in 70 clinical trials showed that among 60,000 patients with estrogen receptor (ER)-positive disease, body mass index (BMI) was associated with risk for breast cancer mortality in both pre- and perimenopausal women.

 But after adjustment for patient factors and tumor characteristics, the association remained significant only for premenopausal women with ER-positive tumors, who had a 34% higher risk of dying from breast cancer, said Dr. Hongchao Pan, on behalf of colleagues in the Early Breast Cancer Trialists’ Collaborative Group.

“To our surprise, we found little independent adverse effects of obesity in the 40,000 postmenopausal women with ER-positive disease,” Dr. Pan said at a media briefing highlighting research to be presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, from May 30 through June 3.

There was also no apparent effect among women of any age with ER-negative tumors.

The findings suggest that the mechanisms by which obesity contributes to breast cancer prognosis are still unclear, Dr. Pan said.

Dr. Peter Yu, president-elect of ASCO and a medical oncologist at Palo Alto Medical Foundation in Sunnyvale, Calif., noted that the study looked only at the role of obesity in breast cancer prognosis, and did not consider its potential contributions to oncogenesis.

“The bottom line, of course, remains that obesity is overall a negative prognostic feature, and something that we will need to address at a societal level,” he said.

Dr. Yu comoderated the briefing, but was not involved in the study.

The other moderator, Dr. Clifford Hudis, president of ASCO and chief of the breast cancer service at Memorial Sloan Kettering Cancer Center, New York, commented that both overweight and obesity are known to contribute to risk for postmenopausal, ER-positive breast cancer.

Obesity is associated with inflammation of white adipose tissue, including adipose tissue of the breast, through up-regulation of inflammatory mediators such as interleukin-6 and prostaglandin. The mediators activate the cytochrome P19 gene, which encodes for the aromatase enzyme, Dr. Hudis explained.

“People who have this low-grade inflammation will have increased aromatase activity, increased local production of estrogen, and that provides an explanation for the paradox of elevated ER-positive breast cancer with obesity after menopause, when the ovaries have stopped higher production of estrogen,” he said.

“I am surprised that the effect was less clear in the postmenopausal than the premenopausal patients [in this study], so I think this is something we’re going to have to explore further,” he said.

Dr. Pan and colleagues collected data on 80,000 individual patients in 70 early breast cancer trials, including information on BMI, ER status, menopausal status, recurrence, and cause of death,

In Cox regression analysis adjusted for age, surgery type, trial treatment, HER-2 receptor status, nodal status, tumor grade, and diameter, they looked at obesity as an independent factor associated with breast cancer mortality.

They found that among premenopausal women, obesity was associated with a relative risk for death of 1.34 (95% confidence interval, 1.22-1.47). In contrast, there was only a weak, nonsignificant effect in postmenopausal, ER-positive women (RR, 1.06; CI, 0.99-1.14), and no effect whatsoever in women with ER-negative tumors (RR, 1.00; CI, 0.93-1.08).

A comparison of obese women (BMI, 30 kg/m² or greater) with those of normal weight (BMI, 20-25) showed 10-year death rates of 21.5% and 16.6%, respectively. The absolute difference at 10 years was 5%, Dr. Pan said.

The study was funded by Cancer Research UK, the Medical Research Council, and the British Heart Foundation. Dr. Pan, Dr. Yu, and Dr. Hudis reported having no relevant financial disclosures.

Obesity appears to increase the risk of breast cancer–related deaths by about one-third in premenopausal but, surprisingly, not postmenopausal women with estrogen receptor–positive disease, investigators report.

An analysis of pooled data on 80,000 patients enrolled in 70 clinical trials showed that among 60,000 patients with estrogen receptor (ER)-positive disease, body mass index (BMI) was associated with risk for breast cancer mortality in both pre- and perimenopausal women.

 But after adjustment for patient factors and tumor characteristics, the association remained significant only for premenopausal women with ER-positive tumors, who had a 34% higher risk of dying from breast cancer, said Dr. Hongchao Pan, on behalf of colleagues in the Early Breast Cancer Trialists’ Collaborative Group.

“To our surprise, we found little independent adverse effects of obesity in the 40,000 postmenopausal women with ER-positive disease,” Dr. Pan said at a media briefing highlighting research to be presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, from May 30 through June 3.

There was also no apparent effect among women of any age with ER-negative tumors.

The findings suggest that the mechanisms by which obesity contributes to breast cancer prognosis are still unclear, Dr. Pan said.

Dr. Peter Yu, president-elect of ASCO and a medical oncologist at Palo Alto Medical Foundation in Sunnyvale, Calif., noted that the study looked only at the role of obesity in breast cancer prognosis, and did not consider its potential contributions to oncogenesis.

“The bottom line, of course, remains that obesity is overall a negative prognostic feature, and something that we will need to address at a societal level,” he said.

Dr. Yu comoderated the briefing, but was not involved in the study.

The other moderator, Dr. Clifford Hudis, president of ASCO and chief of the breast cancer service at Memorial Sloan Kettering Cancer Center, New York, commented that both overweight and obesity are known to contribute to risk for postmenopausal, ER-positive breast cancer.

Obesity is associated with inflammation of white adipose tissue, including adipose tissue of the breast, through up-regulation of inflammatory mediators such as interleukin-6 and prostaglandin. The mediators activate the cytochrome P19 gene, which encodes for the aromatase enzyme, Dr. Hudis explained.

“People who have this low-grade inflammation will have increased aromatase activity, increased local production of estrogen, and that provides an explanation for the paradox of elevated ER-positive breast cancer with obesity after menopause, when the ovaries have stopped higher production of estrogen,” he said.

“I am surprised that the effect was less clear in the postmenopausal than the premenopausal patients [in this study], so I think this is something we’re going to have to explore further,” he said.

Dr. Pan and colleagues collected data on 80,000 individual patients in 70 early breast cancer trials, including information on BMI, ER status, menopausal status, recurrence, and cause of death,

In Cox regression analysis adjusted for age, surgery type, trial treatment, HER-2 receptor status, nodal status, tumor grade, and diameter, they looked at obesity as an independent factor associated with breast cancer mortality.

They found that among premenopausal women, obesity was associated with a relative risk for death of 1.34 (95% confidence interval, 1.22-1.47). In contrast, there was only a weak, nonsignificant effect in postmenopausal, ER-positive women (RR, 1.06; CI, 0.99-1.14), and no effect whatsoever in women with ER-negative tumors (RR, 1.00; CI, 0.93-1.08).

A comparison of obese women (BMI, 30 kg/m² or greater) with those of normal weight (BMI, 20-25) showed 10-year death rates of 21.5% and 16.6%, respectively. The absolute difference at 10 years was 5%, Dr. Pan said.

The study was funded by Cancer Research UK, the Medical Research Council, and the British Heart Foundation. Dr. Pan, Dr. Yu, and Dr. Hudis reported having no relevant financial disclosures.

Delaying the start of androgen-deprivation therapy may be a safe option for men with recurrent prostate cancer marked only by a rise in prostate-specific antigen, investigators report.

Among 2012 men with a prostate-specific antigen (PSA)-only relapse following radical prostatectomy or definitive radiation therapy, the estimated 5-year overall survival for men who deferred androgen-deprivation therapy (ADT) for at least 2 years was 87.2%, compared with 85.1% for men who started on ADT within 3 months of a rising PSA measure, a difference that was not significant, said Dr. Xabier Garcia-De-Albeniz, a research associate at the Harvard School of Public Health in Boston.

“Up to now, we have not had clear evidence, or some evidence,  that delaying treatment until there are more objective signs of disease is a safe thing to do, so this study will now provide us information to have a dialogue between doctors and patients about whether they should start immediate hormone therapy or whether continued observation and waiting might be a better approach,” said Dr. Clifford Hudis at a media briefing highlighting studies to be presented at the American Society of Clinical Oncology (ASCO) 2014 annual meeting in Chicago from May 30 through June 3.

Dr. Hudis, president of ASCO and chief of the breast cancer service at Memorial Sloan-Kettering Cancer Center, New York, comoderated the briefing but was not involved in the study.

There are currently no widely accepted guidelines regarding the best time to start ADT in men with relapsed prostate cancer signaled only by a rise in PSA, with no evidence of recurrent or metastatic disease on imaging.

Dr. Garcia-De-Albeniz noted that ASCO guidelines state “the critical issue is to determine whether there is benefit and how large it is for starting ADT while patients are asymptomatic,” and that National Comprehensive Cancer Network (NCCN) guidelines refer to a “therapeutic dilemma regarding the role of ADT.”

To see whether men with PSA recurrence could be safely spared for a time from the adverse effects of ADT – hot flashes, sexual dysfunction, fracture risk, fatigue, loss of mental acuity, weight gain, depression, etc. – the investigators combed through records from the prospective Cancer of the Prostate Strategic Urologic Research Endeavor (CAPSURE) registry.

Of the more than 14,000 men whose records are included in the database, 2012 had a PSA relapse after therapy with curative intent.

The authors defined PSA relapse as more than  0.2 ng/mL increase in PSA, or three rising determinations 1 month apart. They determined immediate ADT therapy to be treatment within 3 months of PSA relapse, and deferred therapy as ADT started 2 years or more after PSA relapse was first diagnosed or when patients presented with either metastatic disease, symptoms, or a short PSA doubling time (the length of time was not specified).

ADT could be either orchiectomy or the use of a lutenizing hormone–release hormone agonist with or without antiandrogen agents.

As noted before, the investigators found that there was no significant survival advantage to the immediate ADT treatment strategy. After a median follow-up of 41 months, there were 176 deaths, 37 of which were attributable to prostate cancer. The estimated 5-year overall survival was 87.2% for the deferred ADT group, compared with 85.1% for the immediate treatment group. The respective 10-year estimated survival rates were identical, at 71.6%
Similarly, there was no difference in prostate cancer–specific survival, with 5-year rates of 96% and 93.3%, respectively, and 10-year rates of 90.2% and 89.4%.

Dr. Garcia-De-Albeniz acknowledged that because it was an observational rather than randomized study, it is not possible to rule out other, unrecorded characteristics that might have contributed to overall survival, such as differences in blood pressure control, lifestyle choices, and comorbidities.
He noted that there is an ongoing, randomized, phase III trial examining the question of timing of intervention with ADT in men with rising PSA.

The study was supported in part by the National Institutes of Health, ASISA, SEOM (Sociedad Española de Oncología Médica) and an independent educational grant from Abbott. Dr. Garcia-De-Albeniz reported having no financial disclosures.

Delaying the start of androgen-deprivation therapy may be a safe option for men with recurrent prostate cancer marked only by a rise in prostate-specific antigen, investigators report.

Among 2012 men with a prostate-specific antigen (PSA)-only relapse following radical prostatectomy or definitive radiation therapy, the estimated 5-year overall survival for men who deferred androgen-deprivation therapy (ADT) for at least 2 years was 87.2%, compared with 85.1% for men who started on ADT within 3 months of a rising PSA measure, a difference that was not significant, said Dr. Xabier Garcia-De-Albeniz, a research associate at the Harvard School of Public Health in Boston.

“Up to now, we have not had clear evidence, or some evidence,  that delaying treatment until there are more objective signs of disease is a safe thing to do, so this study will now provide us information to have a dialogue between doctors and patients about whether they should start immediate hormone therapy or whether continued observation and waiting might be a better approach,” said Dr. Clifford Hudis at a media briefing highlighting studies to be presented at the American Society of Clinical Oncology (ASCO) 2014 annual meeting in Chicago from May 30 through June 3.

Dr. Hudis, president of ASCO and chief of the breast cancer service at Memorial Sloan-Kettering Cancer Center, New York, comoderated the briefing but was not involved in the study.

There are currently no widely accepted guidelines regarding the best time to start ADT in men with relapsed prostate cancer signaled only by a rise in PSA, with no evidence of recurrent or metastatic disease on imaging.

Dr. Garcia-De-Albeniz noted that ASCO guidelines state “the critical issue is to determine whether there is benefit and how large it is for starting ADT while patients are asymptomatic,” and that National Comprehensive Cancer Network (NCCN) guidelines refer to a “therapeutic dilemma regarding the role of ADT.”

To see whether men with PSA recurrence could be safely spared for a time from the adverse effects of ADT – hot flashes, sexual dysfunction, fracture risk, fatigue, loss of mental acuity, weight gain, depression, etc. – the investigators combed through records from the prospective Cancer of the Prostate Strategic Urologic Research Endeavor (CAPSURE) registry.

Of the more than 14,000 men whose records are included in the database, 2012 had a PSA relapse after therapy with curative intent.

The authors defined PSA relapse as more than  0.2 ng/mL increase in PSA, or three rising determinations 1 month apart. They determined immediate ADT therapy to be treatment within 3 months of PSA relapse, and deferred therapy as ADT started 2 years or more after PSA relapse was first diagnosed or when patients presented with either metastatic disease, symptoms, or a short PSA doubling time (the length of time was not specified).

ADT could be either orchiectomy or the use of a lutenizing hormone–release hormone agonist with or without antiandrogen agents.

As noted before, the investigators found that there was no significant survival advantage to the immediate ADT treatment strategy. After a median follow-up of 41 months, there were 176 deaths, 37 of which were attributable to prostate cancer. The estimated 5-year overall survival was 87.2% for the deferred ADT group, compared with 85.1% for the immediate treatment group. The respective 10-year estimated survival rates were identical, at 71.6%
Similarly, there was no difference in prostate cancer–specific survival, with 5-year rates of 96% and 93.3%, respectively, and 10-year rates of 90.2% and 89.4%.

Dr. Garcia-De-Albeniz acknowledged that because it was an observational rather than randomized study, it is not possible to rule out other, unrecorded characteristics that might have contributed to overall survival, such as differences in blood pressure control, lifestyle choices, and comorbidities.
He noted that there is an ongoing, randomized, phase III trial examining the question of timing of intervention with ADT in men with rising PSA.

The study was supported in part by the National Institutes of Health, ASISA, SEOM (Sociedad Española de Oncología Médica) and an independent educational grant from Abbott. Dr. Garcia-De-Albeniz reported having no financial disclosures.

Delaying the start of androgen-deprivation therapy may be a safe option for men with recurrent prostate cancer marked only by a rise in prostate-specific antigen, investigators report.

Among 2012 men with a prostate-specific antigen (PSA)-only relapse following radical prostatectomy or definitive radiation therapy, the estimated 5-year overall survival for men who deferred androgen-deprivation therapy (ADT) for at least 2 years was 87.2%, compared with 85.1% for men who started on ADT within 3 months of a rising PSA measure, a difference that was not significant, said Dr. Xabier Garcia-De-Albeniz, a research associate at the Harvard School of Public Health in Boston.

“Up to now, we have not had clear evidence, or some evidence,  that delaying treatment until there are more objective signs of disease is a safe thing to do, so this study will now provide us information to have a dialogue between doctors and patients about whether they should start immediate hormone therapy or whether continued observation and waiting might be a better approach,” said Dr. Clifford Hudis at a media briefing highlighting studies to be presented at the American Society of Clinical Oncology (ASCO) 2014 annual meeting in Chicago from May 30 through June 3.

Dr. Hudis, president of ASCO and chief of the breast cancer service at Memorial Sloan-Kettering Cancer Center, New York, comoderated the briefing but was not involved in the study.

There are currently no widely accepted guidelines regarding the best time to start ADT in men with relapsed prostate cancer signaled only by a rise in PSA, with no evidence of recurrent or metastatic disease on imaging.

Dr. Garcia-De-Albeniz noted that ASCO guidelines state “the critical issue is to determine whether there is benefit and how large it is for starting ADT while patients are asymptomatic,” and that National Comprehensive Cancer Network (NCCN) guidelines refer to a “therapeutic dilemma regarding the role of ADT.”

To see whether men with PSA recurrence could be safely spared for a time from the adverse effects of ADT – hot flashes, sexual dysfunction, fracture risk, fatigue, loss of mental acuity, weight gain, depression, etc. – the investigators combed through records from the prospective Cancer of the Prostate Strategic Urologic Research Endeavor (CAPSURE) registry.

Of the more than 14,000 men whose records are included in the database, 2012 had a PSA relapse after therapy with curative intent.

The authors defined PSA relapse as more than  0.2 ng/mL increase in PSA, or three rising determinations 1 month apart. They determined immediate ADT therapy to be treatment within 3 months of PSA relapse, and deferred therapy as ADT started 2 years or more after PSA relapse was first diagnosed or when patients presented with either metastatic disease, symptoms, or a short PSA doubling time (the length of time was not specified).

ADT could be either orchiectomy or the use of a lutenizing hormone–release hormone agonist with or without antiandrogen agents.

As noted before, the investigators found that there was no significant survival advantage to the immediate ADT treatment strategy. After a median follow-up of 41 months, there were 176 deaths, 37 of which were attributable to prostate cancer. The estimated 5-year overall survival was 87.2% for the deferred ADT group, compared with 85.1% for the immediate treatment group. The respective 10-year estimated survival rates were identical, at 71.6%
Similarly, there was no difference in prostate cancer–specific survival, with 5-year rates of 96% and 93.3%, respectively, and 10-year rates of 90.2% and 89.4%.

Dr. Garcia-De-Albeniz acknowledged that because it was an observational rather than randomized study, it is not possible to rule out other, unrecorded characteristics that might have contributed to overall survival, such as differences in blood pressure control, lifestyle choices, and comorbidities.
He noted that there is an ongoing, randomized, phase III trial examining the question of timing of intervention with ADT in men with rising PSA.

The study was supported in part by the National Institutes of Health, ASISA, SEOM (Sociedad Española de Oncología Médica) and an independent educational grant from Abbott. Dr. Garcia-De-Albeniz reported having no financial disclosures.

NEW YORK – A further decline in social functioning of adolescents who already display significant social deficits might be a risk marker for psychosis in adulthood, according to a researcher.

"The inability to function socially appropriately seems to have tremendous potential to be a very early and clear predictor of early mental illness," said Barbara A. Cornblatt, Ph.D., of Zucker Hillside Hospital in New York City.

Dr. Cornblatt distinguishes between functional impairment in the social domain – difficulties making friends, increasing social isolation, lack of social support networks – and role of impairment, which is the "inability to maintain age-appropriate roles in the community."

She and her team follow adolescents and young adults aged 12-22 who are at clinical high risk for psychosis as part of their center’s RAP (Recognition and Prevention) program. They also participate in the NAPLS (North American Prodrome Longitudinal Study) consortium.

They have observed that among clinical high-risk subjects, moderate social problems often are visible early in development, as children join in social activities and try to make friends. Most of these patients appear to have deficits that are stable across development, putting them at risk for future moderate clinical problems and potential disability.

Additionally, there appears to be a subgroup of those with functional social deficits who display a large decline in social interactions typically beginning in their mid-teens, and these progressive deficits might predict later emerging psychosis, Dr. Cornblatt said at the annual meeting of the American Psychiatric Association.

Data from the RAP cohort show on the 10-point social domain of the GAF (Global Assessment of Functioning) Scale, where 1 is extreme social isolation and 10 is superior functioning in a wide range of social and interpersonal relationships, subjects at clinical high risk scored approximately 6, defined as moderate impairment in social functioning, with moderate impairments and moderate difficulty in age-appropriate intimate relationships. In contrast, healthy controls tend to score around 9, deemed to have good functioning in all social areas.

During a mean of 3 years of follow-up, the social scores for clinical high-risk patients remained stable, hovering around 6. The investigators also found that of the measures at baseline, including neurocognition, negative symptoms, role functioning and social functioning, only social functions was predictive of social outcome at follow-up.

"What this says to me is that intervention here is very important. At baseline, when kids are younger, we can intervene and probably affect social functioning using noninvasive, nonpharmacological techniques, for example, neurocognitive remediation or trying to deal with negative symptoms," Dr. Cornblatt said.

As the individual ages, untreated social impairment might become entrenched and much harder to modify, she added. However, she also pointed out that these findings apply to general functioning, because the majority of subjects with social deficits do not go on to develop schizophrenia or other forms of psychosis.

Sharp social declines

There might be a subset of patients who exhibit declines in social skills and interactions from the mid to late teens (16-19) who appear to be at especially high risk for later psychosis, she said.

Dr. Cornblatt noted that in the NAPLS 1 study (Arch. Gen. Psychiatry 2008;65:28-37), decline in social functioning was one of five predictors of psychosis. Similarly, in the RAP phase I cohort, a Cox proportional hazard model controlling for age showed that a decline in social functioning over follow-up also was predictive of psychosis, along with disorganized thoughts, suspiciousness, and verbal memory deficits.

Among 169 patients in the NAPLS 2 cohort who have completed 2 years of follow-up, those who had a social decline of 2 or more points on the GAFS were significantly more likely to convert to psychosis than were patients with a decline of less than 2 (P = .001) (Schizophr. Res. 2012;142:77-82).

"Going down 2 points, from a 7 to a 5, or a 6 to a 4, is a really big change. We’re not talking about trivial social fluctuations; we’re talking about kids (who) have substantial deterioration in their functioning," Dr. Cornblatt said.

She noted that early evidence for a biological underpinning of the observation comes from unpublished data looking at clinical high-risk subjects in NAPLS2 who converted to psychosis. The data showed that growth of ventricles and decrease in gray matter correlated with decline in social functioning. In other words, the larger the ventricles became over time, the worse the decline in social functioning.

The findings "suggest that social problems are one of the areas where it doesn’t matter if the risk is specific for schizophrenia or other forms of psychosis, or just for bad outcome. We should be working to improve the social skills of kids considered at risk from very early ages on," she concluded.

The RAP program is supported by the National Institute of Mental Health and private foundations. Dr. Cornblatt reported having no financial disclosures.

NEW YORK – A further decline in social functioning of adolescents who already display significant social deficits might be a risk marker for psychosis in adulthood, according to a researcher.

"The inability to function socially appropriately seems to have tremendous potential to be a very early and clear predictor of early mental illness," said Barbara A. Cornblatt, Ph.D., of Zucker Hillside Hospital in New York City.

Dr. Cornblatt distinguishes between functional impairment in the social domain – difficulties making friends, increasing social isolation, lack of social support networks – and role of impairment, which is the "inability to maintain age-appropriate roles in the community."

She and her team follow adolescents and young adults aged 12-22 who are at clinical high risk for psychosis as part of their center’s RAP (Recognition and Prevention) program. They also participate in the NAPLS (North American Prodrome Longitudinal Study) consortium.

They have observed that among clinical high-risk subjects, moderate social problems often are visible early in development, as children join in social activities and try to make friends. Most of these patients appear to have deficits that are stable across development, putting them at risk for future moderate clinical problems and potential disability.

Additionally, there appears to be a subgroup of those with functional social deficits who display a large decline in social interactions typically beginning in their mid-teens, and these progressive deficits might predict later emerging psychosis, Dr. Cornblatt said at the annual meeting of the American Psychiatric Association.

Data from the RAP cohort show on the 10-point social domain of the GAF (Global Assessment of Functioning) Scale, where 1 is extreme social isolation and 10 is superior functioning in a wide range of social and interpersonal relationships, subjects at clinical high risk scored approximately 6, defined as moderate impairment in social functioning, with moderate impairments and moderate difficulty in age-appropriate intimate relationships. In contrast, healthy controls tend to score around 9, deemed to have good functioning in all social areas.

During a mean of 3 years of follow-up, the social scores for clinical high-risk patients remained stable, hovering around 6. The investigators also found that of the measures at baseline, including neurocognition, negative symptoms, role functioning and social functioning, only social functions was predictive of social outcome at follow-up.

"What this says to me is that intervention here is very important. At baseline, when kids are younger, we can intervene and probably affect social functioning using noninvasive, nonpharmacological techniques, for example, neurocognitive remediation or trying to deal with negative symptoms," Dr. Cornblatt said.

As the individual ages, untreated social impairment might become entrenched and much harder to modify, she added. However, she also pointed out that these findings apply to general functioning, because the majority of subjects with social deficits do not go on to develop schizophrenia or other forms of psychosis.

Sharp social declines

There might be a subset of patients who exhibit declines in social skills and interactions from the mid to late teens (16-19) who appear to be at especially high risk for later psychosis, she said.

Dr. Cornblatt noted that in the NAPLS 1 study (Arch. Gen. Psychiatry 2008;65:28-37), decline in social functioning was one of five predictors of psychosis. Similarly, in the RAP phase I cohort, a Cox proportional hazard model controlling for age showed that a decline in social functioning over follow-up also was predictive of psychosis, along with disorganized thoughts, suspiciousness, and verbal memory deficits.

Among 169 patients in the NAPLS 2 cohort who have completed 2 years of follow-up, those who had a social decline of 2 or more points on the GAFS were significantly more likely to convert to psychosis than were patients with a decline of less than 2 (P = .001) (Schizophr. Res. 2012;142:77-82).

"Going down 2 points, from a 7 to a 5, or a 6 to a 4, is a really big change. We’re not talking about trivial social fluctuations; we’re talking about kids (who) have substantial deterioration in their functioning," Dr. Cornblatt said.

She noted that early evidence for a biological underpinning of the observation comes from unpublished data looking at clinical high-risk subjects in NAPLS2 who converted to psychosis. The data showed that growth of ventricles and decrease in gray matter correlated with decline in social functioning. In other words, the larger the ventricles became over time, the worse the decline in social functioning.

The findings "suggest that social problems are one of the areas where it doesn’t matter if the risk is specific for schizophrenia or other forms of psychosis, or just for bad outcome. We should be working to improve the social skills of kids considered at risk from very early ages on," she concluded.

The RAP program is supported by the National Institute of Mental Health and private foundations. Dr. Cornblatt reported having no financial disclosures.

NEW YORK – A further decline in social functioning of adolescents who already display significant social deficits might be a risk marker for psychosis in adulthood, according to a researcher.

"The inability to function socially appropriately seems to have tremendous potential to be a very early and clear predictor of early mental illness," said Barbara A. Cornblatt, Ph.D., of Zucker Hillside Hospital in New York City.

Dr. Cornblatt distinguishes between functional impairment in the social domain – difficulties making friends, increasing social isolation, lack of social support networks – and role of impairment, which is the "inability to maintain age-appropriate roles in the community."

She and her team follow adolescents and young adults aged 12-22 who are at clinical high risk for psychosis as part of their center’s RAP (Recognition and Prevention) program. They also participate in the NAPLS (North American Prodrome Longitudinal Study) consortium.

They have observed that among clinical high-risk subjects, moderate social problems often are visible early in development, as children join in social activities and try to make friends. Most of these patients appear to have deficits that are stable across development, putting them at risk for future moderate clinical problems and potential disability.

Additionally, there appears to be a subgroup of those with functional social deficits who display a large decline in social interactions typically beginning in their mid-teens, and these progressive deficits might predict later emerging psychosis, Dr. Cornblatt said at the annual meeting of the American Psychiatric Association.

Data from the RAP cohort show on the 10-point social domain of the GAF (Global Assessment of Functioning) Scale, where 1 is extreme social isolation and 10 is superior functioning in a wide range of social and interpersonal relationships, subjects at clinical high risk scored approximately 6, defined as moderate impairment in social functioning, with moderate impairments and moderate difficulty in age-appropriate intimate relationships. In contrast, healthy controls tend to score around 9, deemed to have good functioning in all social areas.

During a mean of 3 years of follow-up, the social scores for clinical high-risk patients remained stable, hovering around 6. The investigators also found that of the measures at baseline, including neurocognition, negative symptoms, role functioning and social functioning, only social functions was predictive of social outcome at follow-up.

"What this says to me is that intervention here is very important. At baseline, when kids are younger, we can intervene and probably affect social functioning using noninvasive, nonpharmacological techniques, for example, neurocognitive remediation or trying to deal with negative symptoms," Dr. Cornblatt said.

As the individual ages, untreated social impairment might become entrenched and much harder to modify, she added. However, she also pointed out that these findings apply to general functioning, because the majority of subjects with social deficits do not go on to develop schizophrenia or other forms of psychosis.

Sharp social declines

There might be a subset of patients who exhibit declines in social skills and interactions from the mid to late teens (16-19) who appear to be at especially high risk for later psychosis, she said.

Dr. Cornblatt noted that in the NAPLS 1 study (Arch. Gen. Psychiatry 2008;65:28-37), decline in social functioning was one of five predictors of psychosis. Similarly, in the RAP phase I cohort, a Cox proportional hazard model controlling for age showed that a decline in social functioning over follow-up also was predictive of psychosis, along with disorganized thoughts, suspiciousness, and verbal memory deficits.

Among 169 patients in the NAPLS 2 cohort who have completed 2 years of follow-up, those who had a social decline of 2 or more points on the GAFS were significantly more likely to convert to psychosis than were patients with a decline of less than 2 (P = .001) (Schizophr. Res. 2012;142:77-82).

"Going down 2 points, from a 7 to a 5, or a 6 to a 4, is a really big change. We’re not talking about trivial social fluctuations; we’re talking about kids (who) have substantial deterioration in their functioning," Dr. Cornblatt said.

She noted that early evidence for a biological underpinning of the observation comes from unpublished data looking at clinical high-risk subjects in NAPLS2 who converted to psychosis. The data showed that growth of ventricles and decrease in gray matter correlated with decline in social functioning. In other words, the larger the ventricles became over time, the worse the decline in social functioning.

The findings "suggest that social problems are one of the areas where it doesn’t matter if the risk is specific for schizophrenia or other forms of psychosis, or just for bad outcome. We should be working to improve the social skills of kids considered at risk from very early ages on," she concluded.

The RAP program is supported by the National Institute of Mental Health and private foundations. Dr. Cornblatt reported having no financial disclosures.

NEW YORK – Valproic acid might be effective for treating hyperactive delirium, results of a small, retrospective study suggest.

Among 16 patients with hyperactive delirium, 13 had complete resolution of delirium according to the DSM-IV-TR criteria, reported Dr. Yelizaveta I. Sher, an instructor in psychiatry and behavioral science at Stanford (Calif.) University.

"You should definitely consider this medication where antipsychotics are ineffective or there are concerns about side effects from antipsychotics, and you need rapid control of agitation," Dr. Sher said at the annual meeting of the American Psychiatric Association.

Delirium is the most frequent psychiatric diagnosis in general hospital settings and has been reported to occur in up to 85% of patients in intensive care units (ICUs), she noted.

"It prolongs hospital stays and significantly increases morbidity and mortality of these patients," Dr. Sher said.

Antipsychotic agents are usually first-line pharmacological therapies for delirium, but these agents are sometimes ineffective in this setting, and are associated with adverse events such as prolongation of the QT interval, and with extrapyramidal side effects such as akathisia, tremors, and, less frequently, the neuroleptic malignant syndrome, Dr. Sher said.

Antispychotics also are less-than-ideal agents for treatment of agitation associated with acute delirium after traumatic brain injury or from alcohol withdrawal, she added.

Valproic acid is the most widely used agent for the treatment of seizures worldwide, and is approved in the United States for seizures, migraine prophylaxis, and acute manic or mixed bipolar episodes. It often is used off-label for treatment of agitation, neuropathic pain, and personality disorder, according to Dr. Sher.

In addition, its use has been explored in agitated patients with dementia, agitation in traumatic brain injury, and corticosteroid-induced mania.

The use of valproic acid has been associated with neural tube defects in fetuses and must be avoided in women who are pregnant. It also has been associated with mild blood dyscrasias, abnormal liver function tests, and, in patients with urea-cycle enzyme deficiencies, symptomatic hyperammonemia, Dr. Sher cautioned.

Medication interactions with valproic acid include a decrease in blood levels of up to 80% when it is used with meropenem, and an increase in warfarin levels when valproic acid is used with the anticoagulant. Valproic acid also can decrease clearance of carbamazepine, lamotrigine, nortriptyline, and amitriptyline.

Dr. Sher and her colleagues conducted a retrospective study of charts for patients with episodes of hyperactive delirium who were treated with adjunct valproic acid by a consulting or liaison psychiatrist on the psychosomatic medicine service at their center from Aug. 1, 2011, through Aug. 31, 2012. All the patients had hyperactive or mixed delirium as defined by Dr. Benjamin Liptzin’s criteria (Am. J. Psychiatry 1991;148:454-7).

For their investigation, Dr. Sher and her associates reviewed daily notes from the primary ICU team and nurse; daily mental status examination results; daily medication use and doses of psychotropic medications, sedatives, and related medications; daily lab data; descriptions of agitation; and important clinical events such as the use of restraints, extubation, and death.

They identified 16 patients (14 men and 2 women) treated for hyperactive delirium, all but 3 of whom were treated in the ICU. Of this group, 15 patients had received multiple drug treatments for delirium and/or agitation prior to valproic acid use.

The average dose of valproic acid used on days 2-5 was 1,133-1,258 mg per 24 hours in divided daily doses.

As noted before, 13 patients had complete resolution of delirium, at an average of 7.2 days from the start of valproic acid. Two patients had resolution of delirium within 2 days, 4 within 3 days, 2 within 4 days, 1 within 5 days, and the remaining 4 patients at 10, 12 (2 patients), and 31 days.

In all patients, agitation was markedly decreased as rated by mental status examination, agitation scale ratings, and reduced need for sedatives.

In three patients, meropenem might have affected valproic acid levels; two of the patients developed thrombocytopenias.

A randomized controlled trial of valproic acid for the treatment of hyperactive delirium in the ICU is underway, Dr. Sher noted.

The study was internally funded. Dr. Sher reported having no financial disclosures.

NEW YORK – Valproic acid might be effective for treating hyperactive delirium, results of a small, retrospective study suggest.

Among 16 patients with hyperactive delirium, 13 had complete resolution of delirium according to the DSM-IV-TR criteria, reported Dr. Yelizaveta I. Sher, an instructor in psychiatry and behavioral science at Stanford (Calif.) University.

"You should definitely consider this medication where antipsychotics are ineffective or there are concerns about side effects from antipsychotics, and you need rapid control of agitation," Dr. Sher said at the annual meeting of the American Psychiatric Association.

Delirium is the most frequent psychiatric diagnosis in general hospital settings and has been reported to occur in up to 85% of patients in intensive care units (ICUs), she noted.

"It prolongs hospital stays and significantly increases morbidity and mortality of these patients," Dr. Sher said.

Antipsychotic agents are usually first-line pharmacological therapies for delirium, but these agents are sometimes ineffective in this setting, and are associated with adverse events such as prolongation of the QT interval, and with extrapyramidal side effects such as akathisia, tremors, and, less frequently, the neuroleptic malignant syndrome, Dr. Sher said.

Antispychotics also are less-than-ideal agents for treatment of agitation associated with acute delirium after traumatic brain injury or from alcohol withdrawal, she added.

Valproic acid is the most widely used agent for the treatment of seizures worldwide, and is approved in the United States for seizures, migraine prophylaxis, and acute manic or mixed bipolar episodes. It often is used off-label for treatment of agitation, neuropathic pain, and personality disorder, according to Dr. Sher.

In addition, its use has been explored in agitated patients with dementia, agitation in traumatic brain injury, and corticosteroid-induced mania.

The use of valproic acid has been associated with neural tube defects in fetuses and must be avoided in women who are pregnant. It also has been associated with mild blood dyscrasias, abnormal liver function tests, and, in patients with urea-cycle enzyme deficiencies, symptomatic hyperammonemia, Dr. Sher cautioned.

Medication interactions with valproic acid include a decrease in blood levels of up to 80% when it is used with meropenem, and an increase in warfarin levels when valproic acid is used with the anticoagulant. Valproic acid also can decrease clearance of carbamazepine, lamotrigine, nortriptyline, and amitriptyline.

Dr. Sher and her colleagues conducted a retrospective study of charts for patients with episodes of hyperactive delirium who were treated with adjunct valproic acid by a consulting or liaison psychiatrist on the psychosomatic medicine service at their center from Aug. 1, 2011, through Aug. 31, 2012. All the patients had hyperactive or mixed delirium as defined by Dr. Benjamin Liptzin’s criteria (Am. J. Psychiatry 1991;148:454-7).

For their investigation, Dr. Sher and her associates reviewed daily notes from the primary ICU team and nurse; daily mental status examination results; daily medication use and doses of psychotropic medications, sedatives, and related medications; daily lab data; descriptions of agitation; and important clinical events such as the use of restraints, extubation, and death.

They identified 16 patients (14 men and 2 women) treated for hyperactive delirium, all but 3 of whom were treated in the ICU. Of this group, 15 patients had received multiple drug treatments for delirium and/or agitation prior to valproic acid use.

The average dose of valproic acid used on days 2-5 was 1,133-1,258 mg per 24 hours in divided daily doses.

As noted before, 13 patients had complete resolution of delirium, at an average of 7.2 days from the start of valproic acid. Two patients had resolution of delirium within 2 days, 4 within 3 days, 2 within 4 days, 1 within 5 days, and the remaining 4 patients at 10, 12 (2 patients), and 31 days.

In all patients, agitation was markedly decreased as rated by mental status examination, agitation scale ratings, and reduced need for sedatives.

In three patients, meropenem might have affected valproic acid levels; two of the patients developed thrombocytopenias.

A randomized controlled trial of valproic acid for the treatment of hyperactive delirium in the ICU is underway, Dr. Sher noted.

The study was internally funded. Dr. Sher reported having no financial disclosures.

NEW YORK – Valproic acid might be effective for treating hyperactive delirium, results of a small, retrospective study suggest.

Among 16 patients with hyperactive delirium, 13 had complete resolution of delirium according to the DSM-IV-TR criteria, reported Dr. Yelizaveta I. Sher, an instructor in psychiatry and behavioral science at Stanford (Calif.) University.

"You should definitely consider this medication where antipsychotics are ineffective or there are concerns about side effects from antipsychotics, and you need rapid control of agitation," Dr. Sher said at the annual meeting of the American Psychiatric Association.

Delirium is the most frequent psychiatric diagnosis in general hospital settings and has been reported to occur in up to 85% of patients in intensive care units (ICUs), she noted.

"It prolongs hospital stays and significantly increases morbidity and mortality of these patients," Dr. Sher said.

Antipsychotic agents are usually first-line pharmacological therapies for delirium, but these agents are sometimes ineffective in this setting, and are associated with adverse events such as prolongation of the QT interval, and with extrapyramidal side effects such as akathisia, tremors, and, less frequently, the neuroleptic malignant syndrome, Dr. Sher said.

Antispychotics also are less-than-ideal agents for treatment of agitation associated with acute delirium after traumatic brain injury or from alcohol withdrawal, she added.

Valproic acid is the most widely used agent for the treatment of seizures worldwide, and is approved in the United States for seizures, migraine prophylaxis, and acute manic or mixed bipolar episodes. It often is used off-label for treatment of agitation, neuropathic pain, and personality disorder, according to Dr. Sher.

In addition, its use has been explored in agitated patients with dementia, agitation in traumatic brain injury, and corticosteroid-induced mania.

The use of valproic acid has been associated with neural tube defects in fetuses and must be avoided in women who are pregnant. It also has been associated with mild blood dyscrasias, abnormal liver function tests, and, in patients with urea-cycle enzyme deficiencies, symptomatic hyperammonemia, Dr. Sher cautioned.

Medication interactions with valproic acid include a decrease in blood levels of up to 80% when it is used with meropenem, and an increase in warfarin levels when valproic acid is used with the anticoagulant. Valproic acid also can decrease clearance of carbamazepine, lamotrigine, nortriptyline, and amitriptyline.

Dr. Sher and her colleagues conducted a retrospective study of charts for patients with episodes of hyperactive delirium who were treated with adjunct valproic acid by a consulting or liaison psychiatrist on the psychosomatic medicine service at their center from Aug. 1, 2011, through Aug. 31, 2012. All the patients had hyperactive or mixed delirium as defined by Dr. Benjamin Liptzin’s criteria (Am. J. Psychiatry 1991;148:454-7).

For their investigation, Dr. Sher and her associates reviewed daily notes from the primary ICU team and nurse; daily mental status examination results; daily medication use and doses of psychotropic medications, sedatives, and related medications; daily lab data; descriptions of agitation; and important clinical events such as the use of restraints, extubation, and death.

They identified 16 patients (14 men and 2 women) treated for hyperactive delirium, all but 3 of whom were treated in the ICU. Of this group, 15 patients had received multiple drug treatments for delirium and/or agitation prior to valproic acid use.

The average dose of valproic acid used on days 2-5 was 1,133-1,258 mg per 24 hours in divided daily doses.

As noted before, 13 patients had complete resolution of delirium, at an average of 7.2 days from the start of valproic acid. Two patients had resolution of delirium within 2 days, 4 within 3 days, 2 within 4 days, 1 within 5 days, and the remaining 4 patients at 10, 12 (2 patients), and 31 days.

In all patients, agitation was markedly decreased as rated by mental status examination, agitation scale ratings, and reduced need for sedatives.

In three patients, meropenem might have affected valproic acid levels; two of the patients developed thrombocytopenias.

A randomized controlled trial of valproic acid for the treatment of hyperactive delirium in the ICU is underway, Dr. Sher noted.

The study was internally funded. Dr. Sher reported having no financial disclosures.

NEW YORK – The safe, cheap, readily available medication N-acetylcysteine may be effective against difficult-to-treat compulsive grooming disorders, a trans-Atlantic study showed.

In a case series of six patients treated for trichotillomania (hair pulling) and/or skin excoriation (skin-picking disorder, or SPD) as comorbidities to an impulse control or affective disorder, treatment with N-acetylcysteine (NAC) 1,200-1,800 mg/day resulted in either complete abstinence or great improvement in self-damaging habits, said Dr. Gustavo Jesus of the Central Psychiatric Hospital of Lisbon.

Most cases show very good results of the use of NAC in difficult-to-treat grooming disorders, he said at the American Psychiatric Association annual meeting.

Although support for the use of NAC in grooming disorders comes largely from case reports, the available evidence supports his team’s findings, he added.

Neil Osterweil/Frontline Medical News

NAC is a precursor to cysteine, an amino acid that protects cells from oxidative stress, interacts with inflammatory mediators, and is a modulator of the glutaminergic system of neurotransmission.

The medication historically has been used to counteract acetaminophen overdose, as a mucolytic agent for the treatment of respiratory diseases, and in the treatment of contrast-induced nephropathy, polycystic ovary syndrome, and more recently, psychiatric disorders, because of its antioxidative and anti-inflammatory properties.

The agent has been studied most in schizophrenia, Dr. Jesus said, but has also been investigated in bipolar and depressive disorders, substance use problems, obsessive-compulsive disorders and impulse control disorders, including grooming disorders.

Few options

Dr. Jesus’s team, with colleagues in São Paulo, Brazil, reviewed the literature for drug treatment of trichotillomania, and found varying evidence for the use of clomipramine, desipramine, fluoxetine, olanzapine, naltrexone, and citalopram.

"Still, we are short of evidence for which medications can be used to treat grooming disorders," Dr. Jesus said.

He presented data on a case series of three Brazilian and three Portuguese patients, four of whom had SPD, one with trichotillomania, and one with both disorders secondary to conditions that included bipolar disorder, major depressive disorder, generalized anxiety disorder, and dysthymia.

Previous medications tried for their compulsive behaviors included lithium, quetiapine, fluoxetine, venlafaxine, oxcarbazepine, and gabapentin.

Two patients had complete abstinence from SPD for 10-12 months while taking NAC 1,200 mg daily. One of these patients had a relapse after 2 weeks off NAC and improved after restarting the drug. The second patient had a relapse 1 month after stopping the drug and also had improvement after restarting it, this time at a dose of 1,800 mg/day. This patient also had trichotillomania that was considered "greatly improved" with NAC 1,200 mg/day.

The remaining patients all had "great improvement" of SPD, and three had improvement of symptoms when they restarted the drug after hiatuses ranging from 2 weeks to 3 months.

Dr. Jesus emphasized that NAC treated the compulsive grooming symptoms only and not the underlying disorder. For example, one patient with SPD secondary to major depressive disorder also had pathologic jealousy and an addiction to the Internet; NAC did not diminish symptoms of either the jealousy or the addiction.

There has been only one small, randomized, double-blind placebo-controlled trial of NAC in trichotillomania to date, Dr. Jesus noted. The investigators of that study found that patients in the active treatment group had significant improvement of symptoms on both the Massachusetts General Hospital Hair Pulling Scale and the Psychiatric Institute Trichotillomania Scale (P = .001). They also found that more than half of the 50 patients were "much" or "very much" improved with NAC, compared with patients on placebo (P = .003).

Dr. Jesus did not disclose the funding source for the study but reported having no significant financial disclosures or relationships with the manufacturers of any products he discussed.

NEW YORK – The safe, cheap, readily available medication N-acetylcysteine may be effective against difficult-to-treat compulsive grooming disorders, a trans-Atlantic study showed.

In a case series of six patients treated for trichotillomania (hair pulling) and/or skin excoriation (skin-picking disorder, or SPD) as comorbidities to an impulse control or affective disorder, treatment with N-acetylcysteine (NAC) 1,200-1,800 mg/day resulted in either complete abstinence or great improvement in self-damaging habits, said Dr. Gustavo Jesus of the Central Psychiatric Hospital of Lisbon.

Most cases show very good results of the use of NAC in difficult-to-treat grooming disorders, he said at the American Psychiatric Association annual meeting.

Although support for the use of NAC in grooming disorders comes largely from case reports, the available evidence supports his team’s findings, he added.

Neil Osterweil/Frontline Medical News

NAC is a precursor to cysteine, an amino acid that protects cells from oxidative stress, interacts with inflammatory mediators, and is a modulator of the glutaminergic system of neurotransmission.

The medication historically has been used to counteract acetaminophen overdose, as a mucolytic agent for the treatment of respiratory diseases, and in the treatment of contrast-induced nephropathy, polycystic ovary syndrome, and more recently, psychiatric disorders, because of its antioxidative and anti-inflammatory properties.

The agent has been studied most in schizophrenia, Dr. Jesus said, but has also been investigated in bipolar and depressive disorders, substance use problems, obsessive-compulsive disorders and impulse control disorders, including grooming disorders.

Few options

Dr. Jesus’s team, with colleagues in São Paulo, Brazil, reviewed the literature for drug treatment of trichotillomania, and found varying evidence for the use of clomipramine, desipramine, fluoxetine, olanzapine, naltrexone, and citalopram.

"Still, we are short of evidence for which medications can be used to treat grooming disorders," Dr. Jesus said.

He presented data on a case series of three Brazilian and three Portuguese patients, four of whom had SPD, one with trichotillomania, and one with both disorders secondary to conditions that included bipolar disorder, major depressive disorder, generalized anxiety disorder, and dysthymia.

Previous medications tried for their compulsive behaviors included lithium, quetiapine, fluoxetine, venlafaxine, oxcarbazepine, and gabapentin.

Two patients had complete abstinence from SPD for 10-12 months while taking NAC 1,200 mg daily. One of these patients had a relapse after 2 weeks off NAC and improved after restarting the drug. The second patient had a relapse 1 month after stopping the drug and also had improvement after restarting it, this time at a dose of 1,800 mg/day. This patient also had trichotillomania that was considered "greatly improved" with NAC 1,200 mg/day.

The remaining patients all had "great improvement" of SPD, and three had improvement of symptoms when they restarted the drug after hiatuses ranging from 2 weeks to 3 months.

Dr. Jesus emphasized that NAC treated the compulsive grooming symptoms only and not the underlying disorder. For example, one patient with SPD secondary to major depressive disorder also had pathologic jealousy and an addiction to the Internet; NAC did not diminish symptoms of either the jealousy or the addiction.

There has been only one small, randomized, double-blind placebo-controlled trial of NAC in trichotillomania to date, Dr. Jesus noted. The investigators of that study found that patients in the active treatment group had significant improvement of symptoms on both the Massachusetts General Hospital Hair Pulling Scale and the Psychiatric Institute Trichotillomania Scale (P = .001). They also found that more than half of the 50 patients were "much" or "very much" improved with NAC, compared with patients on placebo (P = .003).

Dr. Jesus did not disclose the funding source for the study but reported having no significant financial disclosures or relationships with the manufacturers of any products he discussed.

NEW YORK – The safe, cheap, readily available medication N-acetylcysteine may be effective against difficult-to-treat compulsive grooming disorders, a trans-Atlantic study showed.

In a case series of six patients treated for trichotillomania (hair pulling) and/or skin excoriation (skin-picking disorder, or SPD) as comorbidities to an impulse control or affective disorder, treatment with N-acetylcysteine (NAC) 1,200-1,800 mg/day resulted in either complete abstinence or great improvement in self-damaging habits, said Dr. Gustavo Jesus of the Central Psychiatric Hospital of Lisbon.

Most cases show very good results of the use of NAC in difficult-to-treat grooming disorders, he said at the American Psychiatric Association annual meeting.

Although support for the use of NAC in grooming disorders comes largely from case reports, the available evidence supports his team’s findings, he added.

Neil Osterweil/Frontline Medical News

NAC is a precursor to cysteine, an amino acid that protects cells from oxidative stress, interacts with inflammatory mediators, and is a modulator of the glutaminergic system of neurotransmission.

The medication historically has been used to counteract acetaminophen overdose, as a mucolytic agent for the treatment of respiratory diseases, and in the treatment of contrast-induced nephropathy, polycystic ovary syndrome, and more recently, psychiatric disorders, because of its antioxidative and anti-inflammatory properties.

The agent has been studied most in schizophrenia, Dr. Jesus said, but has also been investigated in bipolar and depressive disorders, substance use problems, obsessive-compulsive disorders and impulse control disorders, including grooming disorders.

Few options

Dr. Jesus’s team, with colleagues in São Paulo, Brazil, reviewed the literature for drug treatment of trichotillomania, and found varying evidence for the use of clomipramine, desipramine, fluoxetine, olanzapine, naltrexone, and citalopram.

"Still, we are short of evidence for which medications can be used to treat grooming disorders," Dr. Jesus said.

He presented data on a case series of three Brazilian and three Portuguese patients, four of whom had SPD, one with trichotillomania, and one with both disorders secondary to conditions that included bipolar disorder, major depressive disorder, generalized anxiety disorder, and dysthymia.

Previous medications tried for their compulsive behaviors included lithium, quetiapine, fluoxetine, venlafaxine, oxcarbazepine, and gabapentin.

Two patients had complete abstinence from SPD for 10-12 months while taking NAC 1,200 mg daily. One of these patients had a relapse after 2 weeks off NAC and improved after restarting the drug. The second patient had a relapse 1 month after stopping the drug and also had improvement after restarting it, this time at a dose of 1,800 mg/day. This patient also had trichotillomania that was considered "greatly improved" with NAC 1,200 mg/day.

The remaining patients all had "great improvement" of SPD, and three had improvement of symptoms when they restarted the drug after hiatuses ranging from 2 weeks to 3 months.

Dr. Jesus emphasized that NAC treated the compulsive grooming symptoms only and not the underlying disorder. For example, one patient with SPD secondary to major depressive disorder also had pathologic jealousy and an addiction to the Internet; NAC did not diminish symptoms of either the jealousy or the addiction.

There has been only one small, randomized, double-blind placebo-controlled trial of NAC in trichotillomania to date, Dr. Jesus noted. The investigators of that study found that patients in the active treatment group had significant improvement of symptoms on both the Massachusetts General Hospital Hair Pulling Scale and the Psychiatric Institute Trichotillomania Scale (P = .001). They also found that more than half of the 50 patients were "much" or "very much" improved with NAC, compared with patients on placebo (P = .003).

Dr. Jesus did not disclose the funding source for the study but reported having no significant financial disclosures or relationships with the manufacturers of any products he discussed.