Kerri Wachter

WASHINGTON – Modified panniculectomy at the time of cesarean section may be a useful adjunct for decreasing postoperative morbidity in morbidly obese patients, based on results of a small case series.

"We found that women who underwent panniculectomy at the time of cesarean section were less likely to have significant wound complications than controls that did not undergo panniculectomy," Dr. Pedro Miranda-Seijo said in a poster presentation at the annual meeting of the American College of Obstetricians and Gynecologists.

He and his coinvestigators conducted a chart review during 2004 that included 30 morbidly obese patients who underwent incidental panniculectomy during cesarean section and a control group of 29 morbidly obese women who underwent a cesarean section without a panniculectomy. The definition of morbidly obese was a body mass index (BMI) of greater than 42 kg/m².

"The decision to perform a panniculectomy was made originally by me before starting surgery, at which time I would obtain informed consent," Dr. Miranda-Seijo said in an interview.

"After I’d done the first 10 or 15 cases, the residents and other attending began trying to schedule elective cases on morbidly obese patients on days that I would be available; often I would see these patients during their antepartum visit and discuss the procedure with them," said Dr. Miranda-Seijo, who is an obstetrician at Denver Health and Hospitals. "I am the only attending that does these procedures; [patients] understand that if they come in labor and I’m not available, they would not be getting a panniculectomy."

Also "when a morbidly obese patient who is in labor needs a cesarean section, if I’m available, I often get called to do it," he said. "If the indication is urgent but not emergent – say failure to descend or secondary arrest of dilation – and I will be available in a few hours, the case is often held for me to do when I arrive," he said.

Notably, the women in this series who underwent panniculectomy had significantly greater BMIs – a mean of 54 vs. 49 kg/m² for the control group.

Of the 30 women who underwent modified panniculectomy at the time of cesarean section, there was one operative site infection that required readmission. In contrast, in the control group there were seven late wound complications and three readmissions. The difference in late wound complications was significant.

There was a nonsignificant difference in operative time, with a mean of 66 minutes with a panniculectomy compared with 63 minutes for cesarean section alone. Panniculectomy did not significantly increase blood loss.

"The extra time needed to infiltrate the skin, remove the pannus, and [close] the large incision is offset by the greater speed achieved in accessing the uterus, delivering the baby, and closing the uterus and fascia, due to better exposure and easier access," Dr. Miranda-Seijo noted.

Several questions were raised by the study: Does the removal of so much adipose tissue have an effect on glucose tolerance, and could this procedure be used by patients as a starting point to initiate healthier lifestyle changes? Additional research will be needed to provide answers, he said.

Dr. Miranda-Seijo reported that he had no relevant financial disclosures.

WASHINGTON – Modified panniculectomy at the time of cesarean section may be a useful adjunct for decreasing postoperative morbidity in morbidly obese patients, based on results of a small case series.

"We found that women who underwent panniculectomy at the time of cesarean section were less likely to have significant wound complications than controls that did not undergo panniculectomy," Dr. Pedro Miranda-Seijo said in a poster presentation at the annual meeting of the American College of Obstetricians and Gynecologists.

He and his coinvestigators conducted a chart review during 2004 that included 30 morbidly obese patients who underwent incidental panniculectomy during cesarean section and a control group of 29 morbidly obese women who underwent a cesarean section without a panniculectomy. The definition of morbidly obese was a body mass index (BMI) of greater than 42 kg/m².

"The decision to perform a panniculectomy was made originally by me before starting surgery, at which time I would obtain informed consent," Dr. Miranda-Seijo said in an interview.

"After I’d done the first 10 or 15 cases, the residents and other attending began trying to schedule elective cases on morbidly obese patients on days that I would be available; often I would see these patients during their antepartum visit and discuss the procedure with them," said Dr. Miranda-Seijo, who is an obstetrician at Denver Health and Hospitals. "I am the only attending that does these procedures; [patients] understand that if they come in labor and I’m not available, they would not be getting a panniculectomy."

Also "when a morbidly obese patient who is in labor needs a cesarean section, if I’m available, I often get called to do it," he said. "If the indication is urgent but not emergent – say failure to descend or secondary arrest of dilation – and I will be available in a few hours, the case is often held for me to do when I arrive," he said.

Notably, the women in this series who underwent panniculectomy had significantly greater BMIs – a mean of 54 vs. 49 kg/m² for the control group.

Of the 30 women who underwent modified panniculectomy at the time of cesarean section, there was one operative site infection that required readmission. In contrast, in the control group there were seven late wound complications and three readmissions. The difference in late wound complications was significant.

There was a nonsignificant difference in operative time, with a mean of 66 minutes with a panniculectomy compared with 63 minutes for cesarean section alone. Panniculectomy did not significantly increase blood loss.

"The extra time needed to infiltrate the skin, remove the pannus, and [close] the large incision is offset by the greater speed achieved in accessing the uterus, delivering the baby, and closing the uterus and fascia, due to better exposure and easier access," Dr. Miranda-Seijo noted.

Several questions were raised by the study: Does the removal of so much adipose tissue have an effect on glucose tolerance, and could this procedure be used by patients as a starting point to initiate healthier lifestyle changes? Additional research will be needed to provide answers, he said.

Dr. Miranda-Seijo reported that he had no relevant financial disclosures.

WASHINGTON – Modified panniculectomy at the time of cesarean section may be a useful adjunct for decreasing postoperative morbidity in morbidly obese patients, based on results of a small case series.

"We found that women who underwent panniculectomy at the time of cesarean section were less likely to have significant wound complications than controls that did not undergo panniculectomy," Dr. Pedro Miranda-Seijo said in a poster presentation at the annual meeting of the American College of Obstetricians and Gynecologists.

He and his coinvestigators conducted a chart review during 2004 that included 30 morbidly obese patients who underwent incidental panniculectomy during cesarean section and a control group of 29 morbidly obese women who underwent a cesarean section without a panniculectomy. The definition of morbidly obese was a body mass index (BMI) of greater than 42 kg/m².

"The decision to perform a panniculectomy was made originally by me before starting surgery, at which time I would obtain informed consent," Dr. Miranda-Seijo said in an interview.

"After I’d done the first 10 or 15 cases, the residents and other attending began trying to schedule elective cases on morbidly obese patients on days that I would be available; often I would see these patients during their antepartum visit and discuss the procedure with them," said Dr. Miranda-Seijo, who is an obstetrician at Denver Health and Hospitals. "I am the only attending that does these procedures; [patients] understand that if they come in labor and I’m not available, they would not be getting a panniculectomy."

Also "when a morbidly obese patient who is in labor needs a cesarean section, if I’m available, I often get called to do it," he said. "If the indication is urgent but not emergent – say failure to descend or secondary arrest of dilation – and I will be available in a few hours, the case is often held for me to do when I arrive," he said.

Notably, the women in this series who underwent panniculectomy had significantly greater BMIs – a mean of 54 vs. 49 kg/m² for the control group.

Of the 30 women who underwent modified panniculectomy at the time of cesarean section, there was one operative site infection that required readmission. In contrast, in the control group there were seven late wound complications and three readmissions. The difference in late wound complications was significant.

There was a nonsignificant difference in operative time, with a mean of 66 minutes with a panniculectomy compared with 63 minutes for cesarean section alone. Panniculectomy did not significantly increase blood loss.

"The extra time needed to infiltrate the skin, remove the pannus, and [close] the large incision is offset by the greater speed achieved in accessing the uterus, delivering the baby, and closing the uterus and fascia, due to better exposure and easier access," Dr. Miranda-Seijo noted.

Several questions were raised by the study: Does the removal of so much adipose tissue have an effect on glucose tolerance, and could this procedure be used by patients as a starting point to initiate healthier lifestyle changes? Additional research will be needed to provide answers, he said.

Dr. Miranda-Seijo reported that he had no relevant financial disclosures.

BALTIMORE – Tumor necrosis of at least 30% following neoadjuvant chemotherapy for hepatoblastoma may predict better event-free and overall survival, based on the results of a small study.

"Histological response to neoadjuvant chemotherapy, as indicated by the percentage of tumor necrosis, is an independent prognostic factor in children with hepatoblastoma, and could potentially be used to modify postsurgical therapy to improve outcomes," lead author Dr. Rajkumar Venkatramani said at the annual meeting of the American Society of Pediatric Hematology/Oncology.

The presence of microscopic residual disease is also an adverse prognostic factor in patients undergoing gross surgical resection, reported Dr. Venkatramani, a fellow at Children’s Hospital Los Angeles.

The researchers conducted a retrospective review of medical records for all children who underwent surgical resection of the primary tumor following neoadjuvant chemotherapy at Children’s Hospital Los Angeles in 1986-2008. In all, 32 patients were included in the study. The investigators studied pathology slides or pretreatment biopsies and surgical resections after neoadjuvant chemotherapy for vascular invasion, positive margins, and tumor necrosis.

The median age at diagnosis was 1.35 years (range, 0-12.7 years), and the group was predominantly male (69%). The median serum AFP (alpha-fetoprotein) level was roughly 300,000 ng/mL. Three-fourths of the group had thrombocytosis at diagnosis, and most patients (81%) had stage III disease per COG (Children’s Oncology Group) criteria.

Most patients (23) received neoadjuvant cisplatin/fluorouracil/vinicristine chemotherapy. The median number of chemotherapy cycles was four.

Gross total resection was performed in 27 patients. Two patients had liver transplant, and three patients had partial resections.

Overall, 7 patients had less than 30% tumor necrosis in the postsurgical sample, 5 had 30%-59%, 9 had 60%-89%, and 11 had at least 90% tumor necrosis. The median tumor necrosis was 70%.

After treatment, seven tumors had evidence of vascular invasion. Most patients (22) had negative pathology margins.

The 3-year event-free survival rate for the entire group was 70%, and the 3-year overall survival rate was 77%. Patients had better event-free and overall survival if they had a greater platelet count at diagnosis, a decline in AFP after four chemotherapy cycles, greater tumor necrosis, complete surgical resection, or negative pathology margins on univariate analysis.

Patients with complete resection and negative margins had the best event-free survival rates, followed by those with complete resection with positive margins. Patients with partial resection had the worst event-free survival. The same pattern was seen for overall survival.

"Those who had greater than or equal to 30% necrosis had a better event-free survival, compared with [those with] less than 30% necrosis," said Dr. Venkatramani. The same was true for overall survival

On multivariate analysis, greater tumor necrosis, greater platelet count at diagnosis, and complete resection with negative margins were all significant predictors of better event-free survival. In the multivariate analysis for overall survival, platelet count at diagnosis dropped out.

The investigators reported that they have no relevant financial relationships.

BALTIMORE – Tumor necrosis of at least 30% following neoadjuvant chemotherapy for hepatoblastoma may predict better event-free and overall survival, based on the results of a small study.

"Histological response to neoadjuvant chemotherapy, as indicated by the percentage of tumor necrosis, is an independent prognostic factor in children with hepatoblastoma, and could potentially be used to modify postsurgical therapy to improve outcomes," lead author Dr. Rajkumar Venkatramani said at the annual meeting of the American Society of Pediatric Hematology/Oncology.

The presence of microscopic residual disease is also an adverse prognostic factor in patients undergoing gross surgical resection, reported Dr. Venkatramani, a fellow at Children’s Hospital Los Angeles.

The researchers conducted a retrospective review of medical records for all children who underwent surgical resection of the primary tumor following neoadjuvant chemotherapy at Children’s Hospital Los Angeles in 1986-2008. In all, 32 patients were included in the study. The investigators studied pathology slides or pretreatment biopsies and surgical resections after neoadjuvant chemotherapy for vascular invasion, positive margins, and tumor necrosis.

The median age at diagnosis was 1.35 years (range, 0-12.7 years), and the group was predominantly male (69%). The median serum AFP (alpha-fetoprotein) level was roughly 300,000 ng/mL. Three-fourths of the group had thrombocytosis at diagnosis, and most patients (81%) had stage III disease per COG (Children’s Oncology Group) criteria.

Most patients (23) received neoadjuvant cisplatin/fluorouracil/vinicristine chemotherapy. The median number of chemotherapy cycles was four.

Gross total resection was performed in 27 patients. Two patients had liver transplant, and three patients had partial resections.

Overall, 7 patients had less than 30% tumor necrosis in the postsurgical sample, 5 had 30%-59%, 9 had 60%-89%, and 11 had at least 90% tumor necrosis. The median tumor necrosis was 70%.

After treatment, seven tumors had evidence of vascular invasion. Most patients (22) had negative pathology margins.

The 3-year event-free survival rate for the entire group was 70%, and the 3-year overall survival rate was 77%. Patients had better event-free and overall survival if they had a greater platelet count at diagnosis, a decline in AFP after four chemotherapy cycles, greater tumor necrosis, complete surgical resection, or negative pathology margins on univariate analysis.

Patients with complete resection and negative margins had the best event-free survival rates, followed by those with complete resection with positive margins. Patients with partial resection had the worst event-free survival. The same pattern was seen for overall survival.

"Those who had greater than or equal to 30% necrosis had a better event-free survival, compared with [those with] less than 30% necrosis," said Dr. Venkatramani. The same was true for overall survival

On multivariate analysis, greater tumor necrosis, greater platelet count at diagnosis, and complete resection with negative margins were all significant predictors of better event-free survival. In the multivariate analysis for overall survival, platelet count at diagnosis dropped out.

The investigators reported that they have no relevant financial relationships.

BALTIMORE – Tumor necrosis of at least 30% following neoadjuvant chemotherapy for hepatoblastoma may predict better event-free and overall survival, based on the results of a small study.

"Histological response to neoadjuvant chemotherapy, as indicated by the percentage of tumor necrosis, is an independent prognostic factor in children with hepatoblastoma, and could potentially be used to modify postsurgical therapy to improve outcomes," lead author Dr. Rajkumar Venkatramani said at the annual meeting of the American Society of Pediatric Hematology/Oncology.

The presence of microscopic residual disease is also an adverse prognostic factor in patients undergoing gross surgical resection, reported Dr. Venkatramani, a fellow at Children’s Hospital Los Angeles.

The researchers conducted a retrospective review of medical records for all children who underwent surgical resection of the primary tumor following neoadjuvant chemotherapy at Children’s Hospital Los Angeles in 1986-2008. In all, 32 patients were included in the study. The investigators studied pathology slides or pretreatment biopsies and surgical resections after neoadjuvant chemotherapy for vascular invasion, positive margins, and tumor necrosis.

The median age at diagnosis was 1.35 years (range, 0-12.7 years), and the group was predominantly male (69%). The median serum AFP (alpha-fetoprotein) level was roughly 300,000 ng/mL. Three-fourths of the group had thrombocytosis at diagnosis, and most patients (81%) had stage III disease per COG (Children’s Oncology Group) criteria.

Most patients (23) received neoadjuvant cisplatin/fluorouracil/vinicristine chemotherapy. The median number of chemotherapy cycles was four.

Gross total resection was performed in 27 patients. Two patients had liver transplant, and three patients had partial resections.

Overall, 7 patients had less than 30% tumor necrosis in the postsurgical sample, 5 had 30%-59%, 9 had 60%-89%, and 11 had at least 90% tumor necrosis. The median tumor necrosis was 70%.

After treatment, seven tumors had evidence of vascular invasion. Most patients (22) had negative pathology margins.

The 3-year event-free survival rate for the entire group was 70%, and the 3-year overall survival rate was 77%. Patients had better event-free and overall survival if they had a greater platelet count at diagnosis, a decline in AFP after four chemotherapy cycles, greater tumor necrosis, complete surgical resection, or negative pathology margins on univariate analysis.

Patients with complete resection and negative margins had the best event-free survival rates, followed by those with complete resection with positive margins. Patients with partial resection had the worst event-free survival. The same pattern was seen for overall survival.

"Those who had greater than or equal to 30% necrosis had a better event-free survival, compared with [those with] less than 30% necrosis," said Dr. Venkatramani. The same was true for overall survival

On multivariate analysis, greater tumor necrosis, greater platelet count at diagnosis, and complete resection with negative margins were all significant predictors of better event-free survival. In the multivariate analysis for overall survival, platelet count at diagnosis dropped out.

The investigators reported that they have no relevant financial relationships.

BALTIMORE – Tumor necrosis of at least 30% following neoadjuvant chemotherapy for hepatoblastoma may predict better event-free and overall survival, based on the results of a small study.

"Histological response to neoadjuvant chemotherapy, as indicated by the percentage of tumor necrosis, is an independent prognostic factor in children with hepatoblastoma, and could potentially be used to modify postsurgical therapy to improve outcomes," lead author Dr. Rajkumar Venkatramani said at the annual meeting of the American Society of Pediatric Hematology/Oncology.

The presence of microscopic residual disease is also an adverse prognostic factor in patients undergoing gross surgical resection, reported Dr. Venkatramani, a fellow at Children’s Hospital Los Angeles.

The researchers conducted a retrospective review of medical records for all children who underwent surgical resection of the primary tumor following neoadjuvant chemotherapy at Children’s Hospital Los Angeles in 1986-2008. In all, 32 patients were included in the study. The investigators studied pathology slides or pretreatment biopsies and surgical resections after neoadjuvant chemotherapy for vascular invasion, positive margins, and tumor necrosis.

The median age at diagnosis was 1.35 years (range, 0-12.7 years), and the group was predominantly male (69%). The median serum AFP (alpha-fetoprotein) level was roughly 300,000 ng/mL. Three-fourths of the group had thrombocytosis at diagnosis, and most patients (81%) had stage III disease per COG (Children’s Oncology Group) criteria.

Most patients (23) received neoadjuvant cisplatin/fluorouracil/vinicristine chemotherapy. The median number of chemotherapy cycles was four.

Gross total resection was performed in 27 patients. Two patients had liver transplant, and three patients had partial resections.

Overall, 7 patients had less than 30% tumor necrosis in the postsurgical sample, 5 had 30%-59%, 9 had 60%-89%, and 11 had at least 90% tumor necrosis. The median tumor necrosis was 70%.

After treatment, seven tumors had evidence of vascular invasion. Most patients (22) had negative pathology margins.

The 3-year event-free survival rate for the entire group was 70%, and the 3-year overall survival rate was 77%. Patients had better event-free and overall survival if they had a greater platelet count at diagnosis, a decline in AFP after four chemotherapy cycles, greater tumor necrosis, complete surgical resection, or negative pathology margins on univariate analysis.

Patients with complete resection and negative margins had the best event-free survival rates, followed by those with complete resection with positive margins. Patients with partial resection had the worst event-free survival. The same pattern was seen for overall survival.

"Those who had greater than or equal to 30% necrosis had a better event-free survival, compared with [those with] less than 30% necrosis," said Dr. Venkatramani. The same was true for overall survival

On multivariate analysis, greater tumor necrosis, greater platelet count at diagnosis, and complete resection with negative margins were all significant predictors of better event-free survival. In the multivariate analysis for overall survival, platelet count at diagnosis dropped out.

The investigators reported that they have no relevant financial relationships.

BALTIMORE – Tumor necrosis of at least 30% following neoadjuvant chemotherapy for hepatoblastoma may predict better event-free and overall survival, based on the results of a small study.

"Histological response to neoadjuvant chemotherapy, as indicated by the percentage of tumor necrosis, is an independent prognostic factor in children with hepatoblastoma, and could potentially be used to modify postsurgical therapy to improve outcomes," lead author Dr. Rajkumar Venkatramani said at the annual meeting of the American Society of Pediatric Hematology/Oncology.

The presence of microscopic residual disease is also an adverse prognostic factor in patients undergoing gross surgical resection, reported Dr. Venkatramani, a fellow at Children’s Hospital Los Angeles.

The researchers conducted a retrospective review of medical records for all children who underwent surgical resection of the primary tumor following neoadjuvant chemotherapy at Children’s Hospital Los Angeles in 1986-2008. In all, 32 patients were included in the study. The investigators studied pathology slides or pretreatment biopsies and surgical resections after neoadjuvant chemotherapy for vascular invasion, positive margins, and tumor necrosis.

The median age at diagnosis was 1.35 years (range, 0-12.7 years), and the group was predominantly male (69%). The median serum AFP (alpha-fetoprotein) level was roughly 300,000 ng/mL. Three-fourths of the group had thrombocytosis at diagnosis, and most patients (81%) had stage III disease per COG (Children’s Oncology Group) criteria.

Most patients (23) received neoadjuvant cisplatin/fluorouracil/vinicristine chemotherapy. The median number of chemotherapy cycles was four.

Gross total resection was performed in 27 patients. Two patients had liver transplant, and three patients had partial resections.

Overall, 7 patients had less than 30% tumor necrosis in the postsurgical sample, 5 had 30%-59%, 9 had 60%-89%, and 11 had at least 90% tumor necrosis. The median tumor necrosis was 70%.

After treatment, seven tumors had evidence of vascular invasion. Most patients (22) had negative pathology margins.

The 3-year event-free survival rate for the entire group was 70%, and the 3-year overall survival rate was 77%. Patients had better event-free and overall survival if they had a greater platelet count at diagnosis, a decline in AFP after four chemotherapy cycles, greater tumor necrosis, complete surgical resection, or negative pathology margins on univariate analysis.

Patients with complete resection and negative margins had the best event-free survival rates, followed by those with complete resection with positive margins. Patients with partial resection had the worst event-free survival. The same pattern was seen for overall survival.

"Those who had greater than or equal to 30% necrosis had a better event-free survival, compared with [those with] less than 30% necrosis," said Dr. Venkatramani. The same was true for overall survival

On multivariate analysis, greater tumor necrosis, greater platelet count at diagnosis, and complete resection with negative margins were all significant predictors of better event-free survival. In the multivariate analysis for overall survival, platelet count at diagnosis dropped out.

The investigators reported that they have no relevant financial relationships.

BALTIMORE – Tumor necrosis of at least 30% following neoadjuvant chemotherapy for hepatoblastoma may predict better event-free and overall survival, based on the results of a small study.

"Histological response to neoadjuvant chemotherapy, as indicated by the percentage of tumor necrosis, is an independent prognostic factor in children with hepatoblastoma, and could potentially be used to modify postsurgical therapy to improve outcomes," lead author Dr. Rajkumar Venkatramani said at the annual meeting of the American Society of Pediatric Hematology/Oncology.

The presence of microscopic residual disease is also an adverse prognostic factor in patients undergoing gross surgical resection, reported Dr. Venkatramani, a fellow at Children’s Hospital Los Angeles.

The researchers conducted a retrospective review of medical records for all children who underwent surgical resection of the primary tumor following neoadjuvant chemotherapy at Children’s Hospital Los Angeles in 1986-2008. In all, 32 patients were included in the study. The investigators studied pathology slides or pretreatment biopsies and surgical resections after neoadjuvant chemotherapy for vascular invasion, positive margins, and tumor necrosis.

The median age at diagnosis was 1.35 years (range, 0-12.7 years), and the group was predominantly male (69%). The median serum AFP (alpha-fetoprotein) level was roughly 300,000 ng/mL. Three-fourths of the group had thrombocytosis at diagnosis, and most patients (81%) had stage III disease per COG (Children’s Oncology Group) criteria.

Most patients (23) received neoadjuvant cisplatin/fluorouracil/vinicristine chemotherapy. The median number of chemotherapy cycles was four.

Gross total resection was performed in 27 patients. Two patients had liver transplant, and three patients had partial resections.

Overall, 7 patients had less than 30% tumor necrosis in the postsurgical sample, 5 had 30%-59%, 9 had 60%-89%, and 11 had at least 90% tumor necrosis. The median tumor necrosis was 70%.

After treatment, seven tumors had evidence of vascular invasion. Most patients (22) had negative pathology margins.

The 3-year event-free survival rate for the entire group was 70%, and the 3-year overall survival rate was 77%. Patients had better event-free and overall survival if they had a greater platelet count at diagnosis, a decline in AFP after four chemotherapy cycles, greater tumor necrosis, complete surgical resection, or negative pathology margins on univariate analysis.

Patients with complete resection and negative margins had the best event-free survival rates, followed by those with complete resection with positive margins. Patients with partial resection had the worst event-free survival. The same pattern was seen for overall survival.

"Those who had greater than or equal to 30% necrosis had a better event-free survival, compared with [those with] less than 30% necrosis," said Dr. Venkatramani. The same was true for overall survival

On multivariate analysis, greater tumor necrosis, greater platelet count at diagnosis, and complete resection with negative margins were all significant predictors of better event-free survival. In the multivariate analysis for overall survival, platelet count at diagnosis dropped out.

The investigators reported that they have no relevant financial relationships.

BALTIMORE – Tumor necrosis of at least 30% following neoadjuvant chemotherapy for hepatoblastoma may predict better event-free and overall survival, based on the results of a small study.

"Histological response to neoadjuvant chemotherapy, as indicated by the percentage of tumor necrosis, is an independent prognostic factor in children with hepatoblastoma, and could potentially be used to modify postsurgical therapy to improve outcomes," lead author Dr. Rajkumar Venkatramani said at the annual meeting of the American Society of Pediatric Hematology/Oncology.

The presence of microscopic residual disease is also an adverse prognostic factor in patients undergoing gross surgical resection, reported Dr. Venkatramani, a fellow at Children’s Hospital Los Angeles.

The researchers conducted a retrospective review of medical records for all children who underwent surgical resection of the primary tumor following neoadjuvant chemotherapy at Children’s Hospital Los Angeles in 1986-2008. In all, 32 patients were included in the study. The investigators studied pathology slides or pretreatment biopsies and surgical resections after neoadjuvant chemotherapy for vascular invasion, positive margins, and tumor necrosis.

The median age at diagnosis was 1.35 years (range, 0-12.7 years), and the group was predominantly male (69%). The median serum AFP (alpha-fetoprotein) level was roughly 300,000 ng/mL. Three-fourths of the group had thrombocytosis at diagnosis, and most patients (81%) had stage III disease per COG (Children’s Oncology Group) criteria.

Most patients (23) received neoadjuvant cisplatin/fluorouracil/vinicristine chemotherapy. The median number of chemotherapy cycles was four.

Gross total resection was performed in 27 patients. Two patients had liver transplant, and three patients had partial resections.

Overall, 7 patients had less than 30% tumor necrosis in the postsurgical sample, 5 had 30%-59%, 9 had 60%-89%, and 11 had at least 90% tumor necrosis. The median tumor necrosis was 70%.

After treatment, seven tumors had evidence of vascular invasion. Most patients (22) had negative pathology margins.

The 3-year event-free survival rate for the entire group was 70%, and the 3-year overall survival rate was 77%. Patients had better event-free and overall survival if they had a greater platelet count at diagnosis, a decline in AFP after four chemotherapy cycles, greater tumor necrosis, complete surgical resection, or negative pathology margins on univariate analysis.

Patients with complete resection and negative margins had the best event-free survival rates, followed by those with complete resection with positive margins. Patients with partial resection had the worst event-free survival. The same pattern was seen for overall survival.

"Those who had greater than or equal to 30% necrosis had a better event-free survival, compared with [those with] less than 30% necrosis," said Dr. Venkatramani. The same was true for overall survival

On multivariate analysis, greater tumor necrosis, greater platelet count at diagnosis, and complete resection with negative margins were all significant predictors of better event-free survival. In the multivariate analysis for overall survival, platelet count at diagnosis dropped out.

The investigators reported that they have no relevant financial relationships.

BALTIMORE – Tumor necrosis of at least 30% following neoadjuvant chemotherapy for hepatoblastoma may predict better event-free and overall survival, based on the results of a small study.

"Histological response to neoadjuvant chemotherapy, as indicated by the percentage of tumor necrosis, is an independent prognostic factor in children with hepatoblastoma, and could potentially be used to modify postsurgical therapy to improve outcomes," lead author Dr. Rajkumar Venkatramani said at the annual meeting of the American Society of Pediatric Hematology/Oncology.

The presence of microscopic residual disease is also an adverse prognostic factor in patients undergoing gross surgical resection, reported Dr. Venkatramani, a fellow at Children’s Hospital Los Angeles.

The researchers conducted a retrospective review of medical records for all children who underwent surgical resection of the primary tumor following neoadjuvant chemotherapy at Children’s Hospital Los Angeles in 1986-2008. In all, 32 patients were included in the study. The investigators studied pathology slides or pretreatment biopsies and surgical resections after neoadjuvant chemotherapy for vascular invasion, positive margins, and tumor necrosis.

The median age at diagnosis was 1.35 years (range, 0-12.7 years), and the group was predominantly male (69%). The median serum AFP (alpha-fetoprotein) level was roughly 300,000 ng/mL. Three-fourths of the group had thrombocytosis at diagnosis, and most patients (81%) had stage III disease per COG (Children’s Oncology Group) criteria.

Most patients (23) received neoadjuvant cisplatin/fluorouracil/vinicristine chemotherapy. The median number of chemotherapy cycles was four.

Gross total resection was performed in 27 patients. Two patients had liver transplant, and three patients had partial resections.

Overall, 7 patients had less than 30% tumor necrosis in the postsurgical sample, 5 had 30%-59%, 9 had 60%-89%, and 11 had at least 90% tumor necrosis. The median tumor necrosis was 70%.

After treatment, seven tumors had evidence of vascular invasion. Most patients (22) had negative pathology margins.

The 3-year event-free survival rate for the entire group was 70%, and the 3-year overall survival rate was 77%. Patients had better event-free and overall survival if they had a greater platelet count at diagnosis, a decline in AFP after four chemotherapy cycles, greater tumor necrosis, complete surgical resection, or negative pathology margins on univariate analysis.

Patients with complete resection and negative margins had the best event-free survival rates, followed by those with complete resection with positive margins. Patients with partial resection had the worst event-free survival. The same pattern was seen for overall survival.

"Those who had greater than or equal to 30% necrosis had a better event-free survival, compared with [those with] less than 30% necrosis," said Dr. Venkatramani. The same was true for overall survival

On multivariate analysis, greater tumor necrosis, greater platelet count at diagnosis, and complete resection with negative margins were all significant predictors of better event-free survival. In the multivariate analysis for overall survival, platelet count at diagnosis dropped out.

The investigators reported that they have no relevant financial relationships.

BALTIMORE – Tumor necrosis of at least 30% following neoadjuvant chemotherapy for hepatoblastoma may predict better event-free and overall survival, based on the results of a small study.

"Histological response to neoadjuvant chemotherapy, as indicated by the percentage of tumor necrosis, is an independent prognostic factor in children with hepatoblastoma, and could potentially be used to modify postsurgical therapy to improve outcomes," lead author Dr. Rajkumar Venkatramani said at the annual meeting of the American Society of Pediatric Hematology/Oncology.

The presence of microscopic residual disease is also an adverse prognostic factor in patients undergoing gross surgical resection, reported Dr. Venkatramani, a fellow at Children’s Hospital Los Angeles.

The researchers conducted a retrospective review of medical records for all children who underwent surgical resection of the primary tumor following neoadjuvant chemotherapy at Children’s Hospital Los Angeles in 1986-2008. In all, 32 patients were included in the study. The investigators studied pathology slides or pretreatment biopsies and surgical resections after neoadjuvant chemotherapy for vascular invasion, positive margins, and tumor necrosis.

The median age at diagnosis was 1.35 years (range, 0-12.7 years), and the group was predominantly male (69%). The median serum AFP (alpha-fetoprotein) level was roughly 300,000 ng/mL. Three-fourths of the group had thrombocytosis at diagnosis, and most patients (81%) had stage III disease per COG (Children’s Oncology Group) criteria.

Most patients (23) received neoadjuvant cisplatin/fluorouracil/vinicristine chemotherapy. The median number of chemotherapy cycles was four.

Gross total resection was performed in 27 patients. Two patients had liver transplant, and three patients had partial resections.

Overall, 7 patients had less than 30% tumor necrosis in the postsurgical sample, 5 had 30%-59%, 9 had 60%-89%, and 11 had at least 90% tumor necrosis. The median tumor necrosis was 70%.

After treatment, seven tumors had evidence of vascular invasion. Most patients (22) had negative pathology margins.

The 3-year event-free survival rate for the entire group was 70%, and the 3-year overall survival rate was 77%. Patients had better event-free and overall survival if they had a greater platelet count at diagnosis, a decline in AFP after four chemotherapy cycles, greater tumor necrosis, complete surgical resection, or negative pathology margins on univariate analysis.

Patients with complete resection and negative margins had the best event-free survival rates, followed by those with complete resection with positive margins. Patients with partial resection had the worst event-free survival. The same pattern was seen for overall survival.

"Those who had greater than or equal to 30% necrosis had a better event-free survival, compared with [those with] less than 30% necrosis," said Dr. Venkatramani. The same was true for overall survival

On multivariate analysis, greater tumor necrosis, greater platelet count at diagnosis, and complete resection with negative margins were all significant predictors of better event-free survival. In the multivariate analysis for overall survival, platelet count at diagnosis dropped out.

The investigators reported that they have no relevant financial relationships.

Major Finding: A single pelvic artery embolization procedure stopped postpartum hemorrhage in 86% of women. A second procedure stopped bleeding in 89%.

Data Source: A retrospective study of 225 women who underwent PAE to stop postpartum hemorrhage.

Disclosures: Dr. Shin reported that he had no relevant financial disclosures.

CHICAGO – Pelvic artery embolization is a highly effective technique for managing postpartum hemorrhage with the added advantage that it preserves the uterus and fertility, according to Dr. Ji Hoon Shin.

In a retrospective study of 225 women who underwent pelvic artery embolization (PAE) to stop postpartum hemorrhage (PPH), a single procedure stopped bleeding in 86% of women. A second procedure stopped bleeding in 89%.

“The major advantage of this procedure is that you can save the uterus and fertility,” Dr. Shin said at the meeting.

Standard therapies include fluid resuscitation/blood transfusion, management of the underlying cause, or surgery – uterine artery ligation, suturing, and hysterectomy.

PAE involves inserting a catheter into the femoral artery via a small incision in the groin. The interventional radiologist can then inject small particles or coils into the arteries to stem hemorrhage. Not only is the technique minimally invasive, it can save the uterus and preserve fertility. While the use of PAE was first reported in 1979, obstetrician awareness of this option is still limited.

In this study, researchers identified 225 patients who underwent pulmonary artery embolization for PPH within 24 hours of delivery between 2000 and 2010. Technical success was defined as cessation of bleeding on postembolization angiogram and cessation of vaginal bleeding on physical inspection. Clinical success was defined as the cessation of bleeding following PAE without the need for additional surgery during the hospital stay.

Uterine atony was the most common cause of PPH in this group (81%). Roughly a third (36%) of patients had positive angiographic findings. Contrast extravasation (a sign of acute bleeding) was seen in most patients (86%) and pseudoaneurysm occurred in 14% of patients, said Dr. Shin of the department of radiology at the University of Ulsan in Seoul, South Korea.

Technical success was 89%. Clinical success with only one PAE procedure was 86% and was 89% when women who had an additional PAE procedure were included. Overall bleeding control – including patients who had repeat PAEs and/or surgeries – was 98%.

In terms of safety, major complications occurred in 2% of patients and included puncture site hematoma and uterine artery dissection. Transient numbness – a minor complication – occurred in 1% of women.

In terms of fertility preservation, 97% of 113 women who were available for follow-up resumed regular menstruation. Irregular menses occurred in two women (2%), and early menopause occurred in one patient (1%). Notably, 11 patients (10%) were able to become pregnant.

On statistical analysis, the presence of disseminated intravascular coagulopathy was the most important negative prognostic factor.

Internal iliac angiography shows contrast extravasation from a cervical branch of the left uterine artery (on left with arrows). Embolization with a microcoil and glue stopped bleeding immediately (right).

Source Photos courtesy Dr. Ji Hoon Shin

Major Finding: A single pelvic artery embolization procedure stopped postpartum hemorrhage in 86% of women. A second procedure stopped bleeding in 89%.

Data Source: A retrospective study of 225 women who underwent PAE to stop postpartum hemorrhage.

Disclosures: Dr. Shin reported that he had no relevant financial disclosures.

CHICAGO – Pelvic artery embolization is a highly effective technique for managing postpartum hemorrhage with the added advantage that it preserves the uterus and fertility, according to Dr. Ji Hoon Shin.

In a retrospective study of 225 women who underwent pelvic artery embolization (PAE) to stop postpartum hemorrhage (PPH), a single procedure stopped bleeding in 86% of women. A second procedure stopped bleeding in 89%.

“The major advantage of this procedure is that you can save the uterus and fertility,” Dr. Shin said at the meeting.

Standard therapies include fluid resuscitation/blood transfusion, management of the underlying cause, or surgery – uterine artery ligation, suturing, and hysterectomy.

PAE involves inserting a catheter into the femoral artery via a small incision in the groin. The interventional radiologist can then inject small particles or coils into the arteries to stem hemorrhage. Not only is the technique minimally invasive, it can save the uterus and preserve fertility. While the use of PAE was first reported in 1979, obstetrician awareness of this option is still limited.

In this study, researchers identified 225 patients who underwent pulmonary artery embolization for PPH within 24 hours of delivery between 2000 and 2010. Technical success was defined as cessation of bleeding on postembolization angiogram and cessation of vaginal bleeding on physical inspection. Clinical success was defined as the cessation of bleeding following PAE without the need for additional surgery during the hospital stay.

Uterine atony was the most common cause of PPH in this group (81%). Roughly a third (36%) of patients had positive angiographic findings. Contrast extravasation (a sign of acute bleeding) was seen in most patients (86%) and pseudoaneurysm occurred in 14% of patients, said Dr. Shin of the department of radiology at the University of Ulsan in Seoul, South Korea.

Technical success was 89%. Clinical success with only one PAE procedure was 86% and was 89% when women who had an additional PAE procedure were included. Overall bleeding control – including patients who had repeat PAEs and/or surgeries – was 98%.

In terms of safety, major complications occurred in 2% of patients and included puncture site hematoma and uterine artery dissection. Transient numbness – a minor complication – occurred in 1% of women.

In terms of fertility preservation, 97% of 113 women who were available for follow-up resumed regular menstruation. Irregular menses occurred in two women (2%), and early menopause occurred in one patient (1%). Notably, 11 patients (10%) were able to become pregnant.

On statistical analysis, the presence of disseminated intravascular coagulopathy was the most important negative prognostic factor.

Internal iliac angiography shows contrast extravasation from a cervical branch of the left uterine artery (on left with arrows). Embolization with a microcoil and glue stopped bleeding immediately (right).

Source Photos courtesy Dr. Ji Hoon Shin

Major Finding: A single pelvic artery embolization procedure stopped postpartum hemorrhage in 86% of women. A second procedure stopped bleeding in 89%.

Data Source: A retrospective study of 225 women who underwent PAE to stop postpartum hemorrhage.

Disclosures: Dr. Shin reported that he had no relevant financial disclosures.

CHICAGO – Pelvic artery embolization is a highly effective technique for managing postpartum hemorrhage with the added advantage that it preserves the uterus and fertility, according to Dr. Ji Hoon Shin.

In a retrospective study of 225 women who underwent pelvic artery embolization (PAE) to stop postpartum hemorrhage (PPH), a single procedure stopped bleeding in 86% of women. A second procedure stopped bleeding in 89%.

“The major advantage of this procedure is that you can save the uterus and fertility,” Dr. Shin said at the meeting.

Standard therapies include fluid resuscitation/blood transfusion, management of the underlying cause, or surgery – uterine artery ligation, suturing, and hysterectomy.

PAE involves inserting a catheter into the femoral artery via a small incision in the groin. The interventional radiologist can then inject small particles or coils into the arteries to stem hemorrhage. Not only is the technique minimally invasive, it can save the uterus and preserve fertility. While the use of PAE was first reported in 1979, obstetrician awareness of this option is still limited.

In this study, researchers identified 225 patients who underwent pulmonary artery embolization for PPH within 24 hours of delivery between 2000 and 2010. Technical success was defined as cessation of bleeding on postembolization angiogram and cessation of vaginal bleeding on physical inspection. Clinical success was defined as the cessation of bleeding following PAE without the need for additional surgery during the hospital stay.

Uterine atony was the most common cause of PPH in this group (81%). Roughly a third (36%) of patients had positive angiographic findings. Contrast extravasation (a sign of acute bleeding) was seen in most patients (86%) and pseudoaneurysm occurred in 14% of patients, said Dr. Shin of the department of radiology at the University of Ulsan in Seoul, South Korea.

Technical success was 89%. Clinical success with only one PAE procedure was 86% and was 89% when women who had an additional PAE procedure were included. Overall bleeding control – including patients who had repeat PAEs and/or surgeries – was 98%.

In terms of safety, major complications occurred in 2% of patients and included puncture site hematoma and uterine artery dissection. Transient numbness – a minor complication – occurred in 1% of women.

In terms of fertility preservation, 97% of 113 women who were available for follow-up resumed regular menstruation. Irregular menses occurred in two women (2%), and early menopause occurred in one patient (1%). Notably, 11 patients (10%) were able to become pregnant.

On statistical analysis, the presence of disseminated intravascular coagulopathy was the most important negative prognostic factor.

Internal iliac angiography shows contrast extravasation from a cervical branch of the left uterine artery (on left with arrows). Embolization with a microcoil and glue stopped bleeding immediately (right).

Source Photos courtesy Dr. Ji Hoon Shin

An international panel has revised the McDonald criteria for the diagnosis of multiple sclerosis to simplify the use of imaging in determining the dissemination of central nervous system lesions both in space and time, while preserving sensitivity and specificity.

The new revisions also address the applicability of the criteria in non-Western Caucasian populations – specifically Asian and Latin American populations – and children and adolescents.

The changes update the 2005 version of the criteria based on new evidence and consensus, which “pointed to the need for their simplification to improve their comprehension and utility and for evaluating their appropriateness in populations that differ from the largely Western Caucasian adult population from which the criteria were derived,” wrote lead author Dr. Chris H. Polman and his coauthors (Ann. Neurol. 2011;69:292-302).

In an accompanying editorial, Dr. Richard A. Rudick agreed (Ann. Neurol. 2011;69:234-6). “The McDonald criteria were not just for clinical trials, but for neurologists in practice. However, some neurologists found the McDonald criteria complex and difficult to use in the clinic, and even experienced MS specialists were uncertain about some aspects of the criteria.” Dr. Rudick is the director of the Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic.

The 2010 revisions to the McDonald criteria are intended to allow a more rapid diagnosis of MS in some instances, with equivalent or improved specificity or sensitivity, and will clarify and simplify the diagnostic process with fewer required MRI examinations, according to Dr. Polman of the neurology department at the Free University in Amsterdam, and his coauthors.

The International Panel on Diagnosis of MS reviewed published research related to the diagnosis of MS and to the original and revised McDonald criteria, gathered from literature searches of English-language publications.

The panel stressed that the updated criteria should be applied only to patients who present with a typical clinically isolated syndrome (CIS) suggestive of MS or symptoms consistent with a central nervous system (CNS) inflammatory demyelinating disease, because the development and validation of the criteria have been limited to patients with such presentations. It also remains imperative that alternative diagnoses be considered and excluded.

Neuromyelitis Optica and Spectrum Disorders

The panel focused on the differential diagnosis for MS of neuromyelitis optica (NMO) and NMO spectrum disorders, because “there is increasing evidence of relapsing CNS demyelinating disease characterized by involvement of optic nerves (unilateral or bilateral optic neuritis), often severe myelopathy with MRI evidence of longitudinally extensive spinal cord lesions, often normal brain MRI (or with abnormalities atypical for MS), and serum aquaporin-4 (AQP4) autoantibodies.”

The panel agreed that this phenotype should be separated out because the clinical course, prognosis, and underlying pathophysiology are different from those of typical MS. The response of patients with NMO and its spectrum disorders to some available MS disease-modifying therapies is often poor.

The panel recommended that this disorder should be carefully considered in the differential diagnosis of all patients presenting with clinical and MRI features that are strongly suggestive of NMO or NMO spectrum disorder, especially if:

▸ Myelopathy is associated with MRI-detected spinal cord lesions longer than three spinal segments and primarily involving the central part of the spinal cord on axial sections;

▸ Optic neuritis is bilateral and severe or associated with a swollen optic nerve or chiasm lesion or an altitudinal scotoma; and

▸ Intractable hiccough, nausea, or vomiting is present for more than 2 days with evidence of a periaqueductal medullary lesion on MRI.

AQP4 serum testing should be used to help make a differential diagnosis between NMO and MS.

Dissemination in Space and Time

While the panel agreed that the underlying concepts of the original (2001) and revised (2005) criteria are still valid, they recommended key changes related to the use and interpretation of imaging criteria for dissemination in space (DIS) and dissemination in time (DIT) as articulated by the recently published work from the Magnetic Imaging in MS (MAGNIMS) research group.

The European MAGNIMS multicenter collaborative research network compared the Barkhof/Tintoré criteria for DIS (Brain 1997;120:2059-69; Am. J. Neuroradiol. 2000;21:702-6) – used in previous McDonald criteria – with simplified criteria developed by Swanton and colleagues (Lancet Neurol. 2007;6: 677-86; J. Neurol. Neurosurg. Psychiatry 2006;77:830-3).

Based on the MAGNIMS analysis, the panel said that DIS can be demonstrated with at least one T2 lesion in at least two of four locations considered characteristic for MS (juxtacortical, periventricular, infratentorial, and spinal cord), excluding lesions within the symptomatic region in patients with brainstem or spinal cord syndromes.

These new criteria for DIS can simplify the diagnostic process for MS, while preserving specificity and improving sensitivity.

The presence of both gadolinium-enhancing and nonenhancing lesions on the baseline MRI can substitute for a follow-up scan to confirm DIT, as long as it can be reliably determined that the gadolinium-enhancing lesion is not due to non-MS pathology.

Based on these changes, a diagnosis of MS can be made in some CIS patients on the basis of a single MRI. The panel stated that this change simplifies the diagnostic process without reducing accuracy.

Cerebrospinal Fluid

The panel still agreed that positive cerebrospinal fluid (CSF) findings – elevated immunoglobulin G (IgG) index or two or more oligoclonal bands – can be important to support the inflammatory demyelinating nature of the underlying condition, to evaluate alternative diagnoses, and to predict clinically definite MS. However, when applying the simplified MAGNIMS imaging criteria for DIS and DIT, the panel believes that changing the MRI requirements in CSF-positive patients is not appropriate.

Primary Progressive MS

The panel recommended replacing previous brain imaging criteria for primary progressive MS (PPMS) with the new MAGNIMS criteria for DIS. In addition to 1 year of disease progression, the new criteria for PPMS require two of the following: at least one T2 lesion in at least one area characteristic for MS (periventricular, juxtacortical, or infratentorial); at least two T2 lesions in the cord; or positive CSF (isoelectric focusing evidence of oligoclonal bands with or without an elevated IgG index).

Dr. Polman, Dr. Rudick, and several other panelists reported significant financial relationships with several pharmaceutical companies.

An international panel has revised the McDonald criteria for the diagnosis of multiple sclerosis to simplify the use of imaging in determining the dissemination of central nervous system lesions both in space and time, while preserving sensitivity and specificity.

The new revisions also address the applicability of the criteria in non-Western Caucasian populations – specifically Asian and Latin American populations – and children and adolescents.

The changes update the 2005 version of the criteria based on new evidence and consensus, which “pointed to the need for their simplification to improve their comprehension and utility and for evaluating their appropriateness in populations that differ from the largely Western Caucasian adult population from which the criteria were derived,” wrote lead author Dr. Chris H. Polman and his coauthors (Ann. Neurol. 2011;69:292-302).

In an accompanying editorial, Dr. Richard A. Rudick agreed (Ann. Neurol. 2011;69:234-6). “The McDonald criteria were not just for clinical trials, but for neurologists in practice. However, some neurologists found the McDonald criteria complex and difficult to use in the clinic, and even experienced MS specialists were uncertain about some aspects of the criteria.” Dr. Rudick is the director of the Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic.

The 2010 revisions to the McDonald criteria are intended to allow a more rapid diagnosis of MS in some instances, with equivalent or improved specificity or sensitivity, and will clarify and simplify the diagnostic process with fewer required MRI examinations, according to Dr. Polman of the neurology department at the Free University in Amsterdam, and his coauthors.

The International Panel on Diagnosis of MS reviewed published research related to the diagnosis of MS and to the original and revised McDonald criteria, gathered from literature searches of English-language publications.

The panel stressed that the updated criteria should be applied only to patients who present with a typical clinically isolated syndrome (CIS) suggestive of MS or symptoms consistent with a central nervous system (CNS) inflammatory demyelinating disease, because the development and validation of the criteria have been limited to patients with such presentations. It also remains imperative that alternative diagnoses be considered and excluded.

Neuromyelitis Optica and Spectrum Disorders

The panel focused on the differential diagnosis for MS of neuromyelitis optica (NMO) and NMO spectrum disorders, because “there is increasing evidence of relapsing CNS demyelinating disease characterized by involvement of optic nerves (unilateral or bilateral optic neuritis), often severe myelopathy with MRI evidence of longitudinally extensive spinal cord lesions, often normal brain MRI (or with abnormalities atypical for MS), and serum aquaporin-4 (AQP4) autoantibodies.”

The panel agreed that this phenotype should be separated out because the clinical course, prognosis, and underlying pathophysiology are different from those of typical MS. The response of patients with NMO and its spectrum disorders to some available MS disease-modifying therapies is often poor.

The panel recommended that this disorder should be carefully considered in the differential diagnosis of all patients presenting with clinical and MRI features that are strongly suggestive of NMO or NMO spectrum disorder, especially if:

▸ Myelopathy is associated with MRI-detected spinal cord lesions longer than three spinal segments and primarily involving the central part of the spinal cord on axial sections;

▸ Optic neuritis is bilateral and severe or associated with a swollen optic nerve or chiasm lesion or an altitudinal scotoma; and

▸ Intractable hiccough, nausea, or vomiting is present for more than 2 days with evidence of a periaqueductal medullary lesion on MRI.

AQP4 serum testing should be used to help make a differential diagnosis between NMO and MS.

Dissemination in Space and Time

While the panel agreed that the underlying concepts of the original (2001) and revised (2005) criteria are still valid, they recommended key changes related to the use and interpretation of imaging criteria for dissemination in space (DIS) and dissemination in time (DIT) as articulated by the recently published work from the Magnetic Imaging in MS (MAGNIMS) research group.

The European MAGNIMS multicenter collaborative research network compared the Barkhof/Tintoré criteria for DIS (Brain 1997;120:2059-69; Am. J. Neuroradiol. 2000;21:702-6) – used in previous McDonald criteria – with simplified criteria developed by Swanton and colleagues (Lancet Neurol. 2007;6: 677-86; J. Neurol. Neurosurg. Psychiatry 2006;77:830-3).

Based on the MAGNIMS analysis, the panel said that DIS can be demonstrated with at least one T2 lesion in at least two of four locations considered characteristic for MS (juxtacortical, periventricular, infratentorial, and spinal cord), excluding lesions within the symptomatic region in patients with brainstem or spinal cord syndromes.

These new criteria for DIS can simplify the diagnostic process for MS, while preserving specificity and improving sensitivity.

The presence of both gadolinium-enhancing and nonenhancing lesions on the baseline MRI can substitute for a follow-up scan to confirm DIT, as long as it can be reliably determined that the gadolinium-enhancing lesion is not due to non-MS pathology.

Based on these changes, a diagnosis of MS can be made in some CIS patients on the basis of a single MRI. The panel stated that this change simplifies the diagnostic process without reducing accuracy.

Cerebrospinal Fluid

The panel still agreed that positive cerebrospinal fluid (CSF) findings – elevated immunoglobulin G (IgG) index or two or more oligoclonal bands – can be important to support the inflammatory demyelinating nature of the underlying condition, to evaluate alternative diagnoses, and to predict clinically definite MS. However, when applying the simplified MAGNIMS imaging criteria for DIS and DIT, the panel believes that changing the MRI requirements in CSF-positive patients is not appropriate.

Primary Progressive MS

The panel recommended replacing previous brain imaging criteria for primary progressive MS (PPMS) with the new MAGNIMS criteria for DIS. In addition to 1 year of disease progression, the new criteria for PPMS require two of the following: at least one T2 lesion in at least one area characteristic for MS (periventricular, juxtacortical, or infratentorial); at least two T2 lesions in the cord; or positive CSF (isoelectric focusing evidence of oligoclonal bands with or without an elevated IgG index).

Dr. Polman, Dr. Rudick, and several other panelists reported significant financial relationships with several pharmaceutical companies.

An international panel has revised the McDonald criteria for the diagnosis of multiple sclerosis to simplify the use of imaging in determining the dissemination of central nervous system lesions both in space and time, while preserving sensitivity and specificity.

The new revisions also address the applicability of the criteria in non-Western Caucasian populations – specifically Asian and Latin American populations – and children and adolescents.

The changes update the 2005 version of the criteria based on new evidence and consensus, which “pointed to the need for their simplification to improve their comprehension and utility and for evaluating their appropriateness in populations that differ from the largely Western Caucasian adult population from which the criteria were derived,” wrote lead author Dr. Chris H. Polman and his coauthors (Ann. Neurol. 2011;69:292-302).

In an accompanying editorial, Dr. Richard A. Rudick agreed (Ann. Neurol. 2011;69:234-6). “The McDonald criteria were not just for clinical trials, but for neurologists in practice. However, some neurologists found the McDonald criteria complex and difficult to use in the clinic, and even experienced MS specialists were uncertain about some aspects of the criteria.” Dr. Rudick is the director of the Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic.

The 2010 revisions to the McDonald criteria are intended to allow a more rapid diagnosis of MS in some instances, with equivalent or improved specificity or sensitivity, and will clarify and simplify the diagnostic process with fewer required MRI examinations, according to Dr. Polman of the neurology department at the Free University in Amsterdam, and his coauthors.

The International Panel on Diagnosis of MS reviewed published research related to the diagnosis of MS and to the original and revised McDonald criteria, gathered from literature searches of English-language publications.

The panel stressed that the updated criteria should be applied only to patients who present with a typical clinically isolated syndrome (CIS) suggestive of MS or symptoms consistent with a central nervous system (CNS) inflammatory demyelinating disease, because the development and validation of the criteria have been limited to patients with such presentations. It also remains imperative that alternative diagnoses be considered and excluded.

Neuromyelitis Optica and Spectrum Disorders

The panel focused on the differential diagnosis for MS of neuromyelitis optica (NMO) and NMO spectrum disorders, because “there is increasing evidence of relapsing CNS demyelinating disease characterized by involvement of optic nerves (unilateral or bilateral optic neuritis), often severe myelopathy with MRI evidence of longitudinally extensive spinal cord lesions, often normal brain MRI (or with abnormalities atypical for MS), and serum aquaporin-4 (AQP4) autoantibodies.”

The panel agreed that this phenotype should be separated out because the clinical course, prognosis, and underlying pathophysiology are different from those of typical MS. The response of patients with NMO and its spectrum disorders to some available MS disease-modifying therapies is often poor.

The panel recommended that this disorder should be carefully considered in the differential diagnosis of all patients presenting with clinical and MRI features that are strongly suggestive of NMO or NMO spectrum disorder, especially if:

▸ Myelopathy is associated with MRI-detected spinal cord lesions longer than three spinal segments and primarily involving the central part of the spinal cord on axial sections;

▸ Optic neuritis is bilateral and severe or associated with a swollen optic nerve or chiasm lesion or an altitudinal scotoma; and

▸ Intractable hiccough, nausea, or vomiting is present for more than 2 days with evidence of a periaqueductal medullary lesion on MRI.

AQP4 serum testing should be used to help make a differential diagnosis between NMO and MS.

Dissemination in Space and Time

While the panel agreed that the underlying concepts of the original (2001) and revised (2005) criteria are still valid, they recommended key changes related to the use and interpretation of imaging criteria for dissemination in space (DIS) and dissemination in time (DIT) as articulated by the recently published work from the Magnetic Imaging in MS (MAGNIMS) research group.

The European MAGNIMS multicenter collaborative research network compared the Barkhof/Tintoré criteria for DIS (Brain 1997;120:2059-69; Am. J. Neuroradiol. 2000;21:702-6) – used in previous McDonald criteria – with simplified criteria developed by Swanton and colleagues (Lancet Neurol. 2007;6: 677-86; J. Neurol. Neurosurg. Psychiatry 2006;77:830-3).

Based on the MAGNIMS analysis, the panel said that DIS can be demonstrated with at least one T2 lesion in at least two of four locations considered characteristic for MS (juxtacortical, periventricular, infratentorial, and spinal cord), excluding lesions within the symptomatic region in patients with brainstem or spinal cord syndromes.

These new criteria for DIS can simplify the diagnostic process for MS, while preserving specificity and improving sensitivity.

The presence of both gadolinium-enhancing and nonenhancing lesions on the baseline MRI can substitute for a follow-up scan to confirm DIT, as long as it can be reliably determined that the gadolinium-enhancing lesion is not due to non-MS pathology.

Based on these changes, a diagnosis of MS can be made in some CIS patients on the basis of a single MRI. The panel stated that this change simplifies the diagnostic process without reducing accuracy.

Cerebrospinal Fluid

The panel still agreed that positive cerebrospinal fluid (CSF) findings – elevated immunoglobulin G (IgG) index or two or more oligoclonal bands – can be important to support the inflammatory demyelinating nature of the underlying condition, to evaluate alternative diagnoses, and to predict clinically definite MS. However, when applying the simplified MAGNIMS imaging criteria for DIS and DIT, the panel believes that changing the MRI requirements in CSF-positive patients is not appropriate.

Primary Progressive MS

The panel recommended replacing previous brain imaging criteria for primary progressive MS (PPMS) with the new MAGNIMS criteria for DIS. In addition to 1 year of disease progression, the new criteria for PPMS require two of the following: at least one T2 lesion in at least one area characteristic for MS (periventricular, juxtacortical, or infratentorial); at least two T2 lesions in the cord; or positive CSF (isoelectric focusing evidence of oligoclonal bands with or without an elevated IgG index).

Dr. Polman, Dr. Rudick, and several other panelists reported significant financial relationships with several pharmaceutical companies.

NATIONAL HARBOR, MD. – Pharmaceutical companies are stepping up to address increasing opioid abuse and misuse by developing innovative abuse-deterrent formulations and drug delivery systems, Dr. Lynn R. Webster said.

Dr. Webster discussed several new opioid formulations that are currently available and some promising technologies in the pipeline. Dr. Webster is board certified in anesthesiology and pain medicine and is certified in addiction medicine. He is also the medical director and founder of the Lifetree Clinical Research and Pain Clinic in Salt Lake City.

New Opioids

In January 2011, the Food and Drug Administration approved Abstral (Prostrakan), a fentanyl transmucosal tablet indicated for the management of breakthrough cancer pain in adults. As an alternative to oral tablets or injections of fentanyl pain medications, the quick-dissolving tablet is placed under the tongue, providing very fast relief for cancer-related pain in patients already receiving opioids for pain treatment.

Approved in 2010, Exalgo is an extended-release formulation of hydromorphone indicated for once-daily administration for the management of moderate to severe pain in opioid-tolerant patients who require continuous, around-the-clock opioid analgesia for an extended period. Exalgo (Mallinckrodt) is not intended for use as an as-needed analgesic. The formulation utilizes a new osmotic, controlled-release oral delivery system in which osmosis attracts water in the body to the inside of the capsule to trigger release of hydromorphone. It takes about 6 hours for effective levels of hydromorphone to be released and 4–5 days for drug levels to reach a steady state in the body, Dr. Webster said.

There has been a resurgence of interest in buprenorphine. This drug has been around for several decades, but is now being used to treat chronic pain. Buprenorphine is a partial mu-opioid agonist, an antagonist at the kappa-opioid receptor, and a partial agonist at the ORL1/nociceptin and delta-opioid receptors. “There is a little bit of complexity with how the pharmacology of this drug works. We probably don't understand clinically what all of that means yet,” Dr. Webster said. Buprenorphine is the only opioid classified as a schedule III drug, making it an attractive choice for pain management. Buprenorphine also is associated with fewer of the side effects typical of opioids, such as respiratory depression.

In 2010, the FDA approved Butrans, an extended-release buprenorphine patch (Purdue Pharma), in 5-, 10- and 20-mcg/hour doses. The drug is indicated for the management of moderate to severe chronic pain in patients requiring continuous, around-the-clock opioid treatment for an extended period.

Notably, Subutex (buprenorphine monotherapy) and Suboxone (a buprenorphine/naloxone combination product) are approved for use in opioid addiction treatment, though other forms of the drug are not. However, other forms of buprenorphine are commonly used off-label for the management of addiction disorders, Dr. Webster said. Because buprenorphine is an opioid partial agonist, its maximal effects are less than those of full agonists (like heroin and methadone). At low doses, buprenorphine is thought to produce enough of an agonist effect to enable opioid-addicted individuals to discontinue the misuse of opioids without experiencing withdrawal symptoms. Buprenorphine has poor oral bioavailability and only moderate sublingual bioavailability.

In the Pipeline

Acurox (Acura Pharmaceuticals and King Pharmaceuticals [now part of Pfizer]) is an oral immediate-release oxycodone tablet with a proposed indication for the relief of moderate to severe pain. Acurox is formulated so that if the tablets are dissolved in an attempt to extract the opioid for intravenous injection, the tablets turn into a viscous gel mixture with the active drug trapped in the gel. The Aversion technology used also causes burning and irritation of the nasal passages if the drug is crushed and snorted.

Last year, the FDA rejected an application for a version of the drug containing niacin, which was formulated so that the uncomfortable “niacin flush” would deter overuse of the drug. In February 2011, the FDA accepted a new drug application for Acurox (oxycodone) tablets without niacin.

MoxDuo (QRxPharma) is an immediate-release dual opioid intended for the acute management of moderate to severe pain. The drug is a combination of morphine and oxycodone that has been clinically shown to have a synergistic effect on pain with a significant reduction of total opioid dose and side effects.

“This formulation is built upon that thought that there are different receptor selectivities to an opioid,” Dr. Webster said. Because opioid receptors differ, “you can get enhanced analgesia with using overall less morphine equivalents, or you could get fewer side effects with the same level of analgesia, when you combine two different opioids.”

Collegium Pharmaceuticals is developing an abuse-deterrent, sustained-release oral oxycodone formulation (COL-003). The DETERx delivery technology consists of a multiparticulate matrix formulation in a capsule designed to be less susceptible to common forms of tampering, such as crushing or chewing prior to ingestion. Company studies showed that the plasma profile for the new-formulation pill was bioequivalent whether it was chewed or taken whole as intended. “It's an abuse-resistant formulation in that they can't extract more than is intended for its delivery,” Dr. Webster said.

Remoxy (Pain Therapeutics and King Pharmaceuticals) is a long-acting oral oxycodone for the treatment of moderate to severe chronic pain. “This is what I consider an opioid-resistant formulation, meaning it's got a barrier that is hard to crush, hard to manipulate; and it's hard to extract” the oxycodone, Dr. Webster said. “It can't be chewed, snorted, or injected very easily.”

A new transmucosal buprenorphine patch is also in the trial phase. According to PharmacoFore, the delivery system's developer, the novel Bio-Activated Molecular Delivery (Bio-MD) technology deters prescription drug abuse at a molecular level.

“This technology does not involve the reformulation of existing opioid drugs in physical matrices that are easily circumvented by simple extraction methods. Our opioid Bio-MD systems are 'activated' to release clinically effective opioid drugs only when exposed to the correct physiologic conditions (i.e., ingested),” the company noted on its Web site.

Essentially, an opioid molecule – any opioid – is attached to the delivery compound. “It's kind of like a clock. The intrinsic trypsin in our GI tract will activate that clock, which will … allow that drug to be released,” Dr. Webster said. The clock determines how much time it takes for the active compound to be released.

“It's very early on,” he cautioned. The delivery system is in phase I trials. Still, “it looks very interesting that they have the technology now to address multipill abuse. There are ways to design the same technologies so that the triggering system will only allow a certain number of pills or milligrams of medication to be absorbed.” Thus, regardless of how many pills an individual takes, no more than the prescribed dose is bioavailable.

Dr. Webster reported that he has significant financial relationships with a number of pharmaceutical companies, including King Pharmaceuticals and Collegium Pharmaceutical.

NATIONAL HARBOR, MD. – Pharmaceutical companies are stepping up to address increasing opioid abuse and misuse by developing innovative abuse-deterrent formulations and drug delivery systems, Dr. Lynn R. Webster said.

Dr. Webster discussed several new opioid formulations that are currently available and some promising technologies in the pipeline. Dr. Webster is board certified in anesthesiology and pain medicine and is certified in addiction medicine. He is also the medical director and founder of the Lifetree Clinical Research and Pain Clinic in Salt Lake City.

New Opioids

In January 2011, the Food and Drug Administration approved Abstral (Prostrakan), a fentanyl transmucosal tablet indicated for the management of breakthrough cancer pain in adults. As an alternative to oral tablets or injections of fentanyl pain medications, the quick-dissolving tablet is placed under the tongue, providing very fast relief for cancer-related pain in patients already receiving opioids for pain treatment.

Approved in 2010, Exalgo is an extended-release formulation of hydromorphone indicated for once-daily administration for the management of moderate to severe pain in opioid-tolerant patients who require continuous, around-the-clock opioid analgesia for an extended period. Exalgo (Mallinckrodt) is not intended for use as an as-needed analgesic. The formulation utilizes a new osmotic, controlled-release oral delivery system in which osmosis attracts water in the body to the inside of the capsule to trigger release of hydromorphone. It takes about 6 hours for effective levels of hydromorphone to be released and 4–5 days for drug levels to reach a steady state in the body, Dr. Webster said.

There has been a resurgence of interest in buprenorphine. This drug has been around for several decades, but is now being used to treat chronic pain. Buprenorphine is a partial mu-opioid agonist, an antagonist at the kappa-opioid receptor, and a partial agonist at the ORL1/nociceptin and delta-opioid receptors. “There is a little bit of complexity with how the pharmacology of this drug works. We probably don't understand clinically what all of that means yet,” Dr. Webster said. Buprenorphine is the only opioid classified as a schedule III drug, making it an attractive choice for pain management. Buprenorphine also is associated with fewer of the side effects typical of opioids, such as respiratory depression.

In 2010, the FDA approved Butrans, an extended-release buprenorphine patch (Purdue Pharma), in 5-, 10- and 20-mcg/hour doses. The drug is indicated for the management of moderate to severe chronic pain in patients requiring continuous, around-the-clock opioid treatment for an extended period.

Notably, Subutex (buprenorphine monotherapy) and Suboxone (a buprenorphine/naloxone combination product) are approved for use in opioid addiction treatment, though other forms of the drug are not. However, other forms of buprenorphine are commonly used off-label for the management of addiction disorders, Dr. Webster said. Because buprenorphine is an opioid partial agonist, its maximal effects are less than those of full agonists (like heroin and methadone). At low doses, buprenorphine is thought to produce enough of an agonist effect to enable opioid-addicted individuals to discontinue the misuse of opioids without experiencing withdrawal symptoms. Buprenorphine has poor oral bioavailability and only moderate sublingual bioavailability.

In the Pipeline

Acurox (Acura Pharmaceuticals and King Pharmaceuticals [now part of Pfizer]) is an oral immediate-release oxycodone tablet with a proposed indication for the relief of moderate to severe pain. Acurox is formulated so that if the tablets are dissolved in an attempt to extract the opioid for intravenous injection, the tablets turn into a viscous gel mixture with the active drug trapped in the gel. The Aversion technology used also causes burning and irritation of the nasal passages if the drug is crushed and snorted.

Last year, the FDA rejected an application for a version of the drug containing niacin, which was formulated so that the uncomfortable “niacin flush” would deter overuse of the drug. In February 2011, the FDA accepted a new drug application for Acurox (oxycodone) tablets without niacin.

MoxDuo (QRxPharma) is an immediate-release dual opioid intended for the acute management of moderate to severe pain. The drug is a combination of morphine and oxycodone that has been clinically shown to have a synergistic effect on pain with a significant reduction of total opioid dose and side effects.

“This formulation is built upon that thought that there are different receptor selectivities to an opioid,” Dr. Webster said. Because opioid receptors differ, “you can get enhanced analgesia with using overall less morphine equivalents, or you could get fewer side effects with the same level of analgesia, when you combine two different opioids.”

Collegium Pharmaceuticals is developing an abuse-deterrent, sustained-release oral oxycodone formulation (COL-003). The DETERx delivery technology consists of a multiparticulate matrix formulation in a capsule designed to be less susceptible to common forms of tampering, such as crushing or chewing prior to ingestion. Company studies showed that the plasma profile for the new-formulation pill was bioequivalent whether it was chewed or taken whole as intended. “It's an abuse-resistant formulation in that they can't extract more than is intended for its delivery,” Dr. Webster said.

Remoxy (Pain Therapeutics and King Pharmaceuticals) is a long-acting oral oxycodone for the treatment of moderate to severe chronic pain. “This is what I consider an opioid-resistant formulation, meaning it's got a barrier that is hard to crush, hard to manipulate; and it's hard to extract” the oxycodone, Dr. Webster said. “It can't be chewed, snorted, or injected very easily.”

A new transmucosal buprenorphine patch is also in the trial phase. According to PharmacoFore, the delivery system's developer, the novel Bio-Activated Molecular Delivery (Bio-MD) technology deters prescription drug abuse at a molecular level.

“This technology does not involve the reformulation of existing opioid drugs in physical matrices that are easily circumvented by simple extraction methods. Our opioid Bio-MD systems are 'activated' to release clinically effective opioid drugs only when exposed to the correct physiologic conditions (i.e., ingested),” the company noted on its Web site.

Essentially, an opioid molecule – any opioid – is attached to the delivery compound. “It's kind of like a clock. The intrinsic trypsin in our GI tract will activate that clock, which will … allow that drug to be released,” Dr. Webster said. The clock determines how much time it takes for the active compound to be released.

“It's very early on,” he cautioned. The delivery system is in phase I trials. Still, “it looks very interesting that they have the technology now to address multipill abuse. There are ways to design the same technologies so that the triggering system will only allow a certain number of pills or milligrams of medication to be absorbed.” Thus, regardless of how many pills an individual takes, no more than the prescribed dose is bioavailable.

Dr. Webster reported that he has significant financial relationships with a number of pharmaceutical companies, including King Pharmaceuticals and Collegium Pharmaceutical.

NATIONAL HARBOR, MD. – Pharmaceutical companies are stepping up to address increasing opioid abuse and misuse by developing innovative abuse-deterrent formulations and drug delivery systems, Dr. Lynn R. Webster said.

Dr. Webster discussed several new opioid formulations that are currently available and some promising technologies in the pipeline. Dr. Webster is board certified in anesthesiology and pain medicine and is certified in addiction medicine. He is also the medical director and founder of the Lifetree Clinical Research and Pain Clinic in Salt Lake City.

New Opioids

In January 2011, the Food and Drug Administration approved Abstral (Prostrakan), a fentanyl transmucosal tablet indicated for the management of breakthrough cancer pain in adults. As an alternative to oral tablets or injections of fentanyl pain medications, the quick-dissolving tablet is placed under the tongue, providing very fast relief for cancer-related pain in patients already receiving opioids for pain treatment.

Approved in 2010, Exalgo is an extended-release formulation of hydromorphone indicated for once-daily administration for the management of moderate to severe pain in opioid-tolerant patients who require continuous, around-the-clock opioid analgesia for an extended period. Exalgo (Mallinckrodt) is not intended for use as an as-needed analgesic. The formulation utilizes a new osmotic, controlled-release oral delivery system in which osmosis attracts water in the body to the inside of the capsule to trigger release of hydromorphone. It takes about 6 hours for effective levels of hydromorphone to be released and 4–5 days for drug levels to reach a steady state in the body, Dr. Webster said.

There has been a resurgence of interest in buprenorphine. This drug has been around for several decades, but is now being used to treat chronic pain. Buprenorphine is a partial mu-opioid agonist, an antagonist at the kappa-opioid receptor, and a partial agonist at the ORL1/nociceptin and delta-opioid receptors. “There is a little bit of complexity with how the pharmacology of this drug works. We probably don't understand clinically what all of that means yet,” Dr. Webster said. Buprenorphine is the only opioid classified as a schedule III drug, making it an attractive choice for pain management. Buprenorphine also is associated with fewer of the side effects typical of opioids, such as respiratory depression.

In 2010, the FDA approved Butrans, an extended-release buprenorphine patch (Purdue Pharma), in 5-, 10- and 20-mcg/hour doses. The drug is indicated for the management of moderate to severe chronic pain in patients requiring continuous, around-the-clock opioid treatment for an extended period.

Notably, Subutex (buprenorphine monotherapy) and Suboxone (a buprenorphine/naloxone combination product) are approved for use in opioid addiction treatment, though other forms of the drug are not. However, other forms of buprenorphine are commonly used off-label for the management of addiction disorders, Dr. Webster said. Because buprenorphine is an opioid partial agonist, its maximal effects are less than those of full agonists (like heroin and methadone). At low doses, buprenorphine is thought to produce enough of an agonist effect to enable opioid-addicted individuals to discontinue the misuse of opioids without experiencing withdrawal symptoms. Buprenorphine has poor oral bioavailability and only moderate sublingual bioavailability.

In the Pipeline

Acurox (Acura Pharmaceuticals and King Pharmaceuticals [now part of Pfizer]) is an oral immediate-release oxycodone tablet with a proposed indication for the relief of moderate to severe pain. Acurox is formulated so that if the tablets are dissolved in an attempt to extract the opioid for intravenous injection, the tablets turn into a viscous gel mixture with the active drug trapped in the gel. The Aversion technology used also causes burning and irritation of the nasal passages if the drug is crushed and snorted.

Last year, the FDA rejected an application for a version of the drug containing niacin, which was formulated so that the uncomfortable “niacin flush” would deter overuse of the drug. In February 2011, the FDA accepted a new drug application for Acurox (oxycodone) tablets without niacin.

MoxDuo (QRxPharma) is an immediate-release dual opioid intended for the acute management of moderate to severe pain. The drug is a combination of morphine and oxycodone that has been clinically shown to have a synergistic effect on pain with a significant reduction of total opioid dose and side effects.

“This formulation is built upon that thought that there are different receptor selectivities to an opioid,” Dr. Webster said. Because opioid receptors differ, “you can get enhanced analgesia with using overall less morphine equivalents, or you could get fewer side effects with the same level of analgesia, when you combine two different opioids.”

Collegium Pharmaceuticals is developing an abuse-deterrent, sustained-release oral oxycodone formulation (COL-003). The DETERx delivery technology consists of a multiparticulate matrix formulation in a capsule designed to be less susceptible to common forms of tampering, such as crushing or chewing prior to ingestion. Company studies showed that the plasma profile for the new-formulation pill was bioequivalent whether it was chewed or taken whole as intended. “It's an abuse-resistant formulation in that they can't extract more than is intended for its delivery,” Dr. Webster said.

Remoxy (Pain Therapeutics and King Pharmaceuticals) is a long-acting oral oxycodone for the treatment of moderate to severe chronic pain. “This is what I consider an opioid-resistant formulation, meaning it's got a barrier that is hard to crush, hard to manipulate; and it's hard to extract” the oxycodone, Dr. Webster said. “It can't be chewed, snorted, or injected very easily.”

A new transmucosal buprenorphine patch is also in the trial phase. According to PharmacoFore, the delivery system's developer, the novel Bio-Activated Molecular Delivery (Bio-MD) technology deters prescription drug abuse at a molecular level.

“This technology does not involve the reformulation of existing opioid drugs in physical matrices that are easily circumvented by simple extraction methods. Our opioid Bio-MD systems are 'activated' to release clinically effective opioid drugs only when exposed to the correct physiologic conditions (i.e., ingested),” the company noted on its Web site.

Essentially, an opioid molecule – any opioid – is attached to the delivery compound. “It's kind of like a clock. The intrinsic trypsin in our GI tract will activate that clock, which will … allow that drug to be released,” Dr. Webster said. The clock determines how much time it takes for the active compound to be released.

“It's very early on,” he cautioned. The delivery system is in phase I trials. Still, “it looks very interesting that they have the technology now to address multipill abuse. There are ways to design the same technologies so that the triggering system will only allow a certain number of pills or milligrams of medication to be absorbed.” Thus, regardless of how many pills an individual takes, no more than the prescribed dose is bioavailable.

Dr. Webster reported that he has significant financial relationships with a number of pharmaceutical companies, including King Pharmaceuticals and Collegium Pharmaceutical.

Dermatologists may not have to use Restylane off label for lip augmentation any longer. On April 27, a Food and Drug Administration panel voted 6-0 with 1 abstention that benefits outweigh risks for using the filler as a submucosal injection for lip augmentation.

The panel also voted 6-0 with 1 abstention that the filler is safe and effective for the expanded indication.

Restylane (Medicis Aesthetics) is a hyaluronic acid gel generated by Streptococcus bacteria, chemically crosslinked with 1,4 butanediol diglycidyl ether. The filler was first approved in 2005 for mid-to-deep dermal implantation for the correction of moderate-to-severe facial wrinkles and folds, such as nasolabial folds.

Medicis recently conducted a clinical study (MA-1399-15) to evaluate the safety and effectiveness of the filler in the augmentation of soft tissue fullness of the lips. The study included 135 patients, who received lip augmentation with Restylane, and 45 patients with no treatment. The mean volume of filler was 2.9 cc per patient, with a range of 0.6-5.6 cc per patient. At 8 weeks, 92% of patients who received Restylane were considered responders.

Adverse events occurred in 99% of patients. Expected treatment-emergent adverse events included bruising, redness, swelling, pain, tenderness, itching, and skin exfoliation. Of note, herpes simplex virus 1 outbreaks occurred in 4% of patients. The outbreaks were determined to be associated with injection of the filler in 7 or 10 cases.

Forty percent of patients who received the filler had adverse outcomes that they felt affected their daily activity or were disabling; 15% of Restylane patients experienced adverse events (typically swelling and tenderness) that lasted more than 15 days.

The agency was particularly concerned about the implications of the treatment in younger patients who may still be growing and are likely to receive repeat treatments over time.

"My only problem with voting completely yes ... is that I don’t think that the question was worded in such a way that I felt totally comfortable giving my final approval for safety, efficacy, and risk/benefit ratio to all populations," said panel member Dr. Delora L. Mount, associate professor of surgery and pediatrics at the University of Wisconsin in Madison.

The FDA panel was also concerned about the lack of men and individuals with dark skin in the trial. Only one man was included and 38 individuals were Fitzpatrick skin type IV, 3 individuals were type V, and none were type VI.

The FDA usually follows its panels’ advice, but is not obligated to do so.

Dermatologists may not have to use Restylane off label for lip augmentation any longer. On April 27, a Food and Drug Administration panel voted 6-0 with 1 abstention that benefits outweigh risks for using the filler as a submucosal injection for lip augmentation.

The panel also voted 6-0 with 1 abstention that the filler is safe and effective for the expanded indication.

Restylane (Medicis Aesthetics) is a hyaluronic acid gel generated by Streptococcus bacteria, chemically crosslinked with 1,4 butanediol diglycidyl ether. The filler was first approved in 2005 for mid-to-deep dermal implantation for the correction of moderate-to-severe facial wrinkles and folds, such as nasolabial folds.

Medicis recently conducted a clinical study (MA-1399-15) to evaluate the safety and effectiveness of the filler in the augmentation of soft tissue fullness of the lips. The study included 135 patients, who received lip augmentation with Restylane, and 45 patients with no treatment. The mean volume of filler was 2.9 cc per patient, with a range of 0.6-5.6 cc per patient. At 8 weeks, 92% of patients who received Restylane were considered responders.

Adverse events occurred in 99% of patients. Expected treatment-emergent adverse events included bruising, redness, swelling, pain, tenderness, itching, and skin exfoliation. Of note, herpes simplex virus 1 outbreaks occurred in 4% of patients. The outbreaks were determined to be associated with injection of the filler in 7 or 10 cases.

Forty percent of patients who received the filler had adverse outcomes that they felt affected their daily activity or were disabling; 15% of Restylane patients experienced adverse events (typically swelling and tenderness) that lasted more than 15 days.

The agency was particularly concerned about the implications of the treatment in younger patients who may still be growing and are likely to receive repeat treatments over time.

"My only problem with voting completely yes ... is that I don’t think that the question was worded in such a way that I felt totally comfortable giving my final approval for safety, efficacy, and risk/benefit ratio to all populations," said panel member Dr. Delora L. Mount, associate professor of surgery and pediatrics at the University of Wisconsin in Madison.

The FDA panel was also concerned about the lack of men and individuals with dark skin in the trial. Only one man was included and 38 individuals were Fitzpatrick skin type IV, 3 individuals were type V, and none were type VI.

The FDA usually follows its panels’ advice, but is not obligated to do so.

Dermatologists may not have to use Restylane off label for lip augmentation any longer. On April 27, a Food and Drug Administration panel voted 6-0 with 1 abstention that benefits outweigh risks for using the filler as a submucosal injection for lip augmentation.

The panel also voted 6-0 with 1 abstention that the filler is safe and effective for the expanded indication.

Restylane (Medicis Aesthetics) is a hyaluronic acid gel generated by Streptococcus bacteria, chemically crosslinked with 1,4 butanediol diglycidyl ether. The filler was first approved in 2005 for mid-to-deep dermal implantation for the correction of moderate-to-severe facial wrinkles and folds, such as nasolabial folds.

Medicis recently conducted a clinical study (MA-1399-15) to evaluate the safety and effectiveness of the filler in the augmentation of soft tissue fullness of the lips. The study included 135 patients, who received lip augmentation with Restylane, and 45 patients with no treatment. The mean volume of filler was 2.9 cc per patient, with a range of 0.6-5.6 cc per patient. At 8 weeks, 92% of patients who received Restylane were considered responders.

Adverse events occurred in 99% of patients. Expected treatment-emergent adverse events included bruising, redness, swelling, pain, tenderness, itching, and skin exfoliation. Of note, herpes simplex virus 1 outbreaks occurred in 4% of patients. The outbreaks were determined to be associated with injection of the filler in 7 or 10 cases.

Forty percent of patients who received the filler had adverse outcomes that they felt affected their daily activity or were disabling; 15% of Restylane patients experienced adverse events (typically swelling and tenderness) that lasted more than 15 days.

The agency was particularly concerned about the implications of the treatment in younger patients who may still be growing and are likely to receive repeat treatments over time.

"My only problem with voting completely yes ... is that I don’t think that the question was worded in such a way that I felt totally comfortable giving my final approval for safety, efficacy, and risk/benefit ratio to all populations," said panel member Dr. Delora L. Mount, associate professor of surgery and pediatrics at the University of Wisconsin in Madison.

The FDA panel was also concerned about the lack of men and individuals with dark skin in the trial. Only one man was included and 38 individuals were Fitzpatrick skin type IV, 3 individuals were type V, and none were type VI.

The FDA usually follows its panels’ advice, but is not obligated to do so.

Dermatologists may not have to use Restylane off-label for lip augmentation any longer. A Food and Drug Administration panel voted 6-0 with 1 abstention that benefits outweigh risks for using the filler as a submucosal injection for lip augmentation on April 27.

The panel also voted 6-0 with 1 abstention that the filler is safe and effective for the expanded indication.

Restylane (Medicis Aesthetics) is a hyaluronic acid gel generated by Streptococcus bacteria, chemically crosslinked with 1,4 butanediol diglycidyl ether. The filler was first approved in 2005 for mid-to-deep dermal implantation for the correction of moderate-to-severe facial wrinkles and folds, such as nasolabial folds.

Medicis recently conducted a clinical study (MA-1399-15) to evaluate the safety and effectiveness of the filler in the augmentation of soft tissue fullness of the lips. The study included 135 patients, who received lip augmentation with Restylane, and 45 patients with no treatment. The mean volume of filler was 2.9 cc per patient, with a range of 0.6 -5.6 cc per patient. At 8 weeks, 92% of patients who received Restylane were considered responders.

Adverse events occurred in 99% of patients. Expected treatment-emergent adverse events included bruising, redness, swelling, pain, tenderness, itching, and skin exfoliation. Of note, herpes simplex virus 1 outbreaks occurred in 4% of patients. The outbreaks were determined to be associated with injection of the filler in 7 or 10 cases.

Forty percent of patients who received the filler had adverse outcomes that they felt affected their daily activity or were disabling; 15% of Restylane patients experienced adverse events (typically swelling and tenderness) that lasted more than 15 days.

The panel was particularly concerned about the implications of the treatment in younger patients who may still be growing and are likely to receive repeat treatments over time.

"My only problem with voting completely yes … is that I don't think that the question was worded in such a way that I felt totally comfortable giving my final approval for safety, efficacy, and risk/benefit ratio to all populations," said panel member Dr. Delora L. Mount, who is an associate professor of surgery and pediatrics at the University of Wisconsin in Madison.

The FDA panel was also concerned about the lack of men and individuals with dark skin in the trial. Only one man was included and 38 individuals were Fitzpatrick skin type IV, 3 individuals were type V, and none were type VI.

The FDA usually follows its panels' advice, but is not obligated to do so.

Dermatologists may not have to use Restylane off-label for lip augmentation any longer. A Food and Drug Administration panel voted 6-0 with 1 abstention that benefits outweigh risks for using the filler as a submucosal injection for lip augmentation on April 27.

The panel also voted 6-0 with 1 abstention that the filler is safe and effective for the expanded indication.

Restylane (Medicis Aesthetics) is a hyaluronic acid gel generated by Streptococcus bacteria, chemically crosslinked with 1,4 butanediol diglycidyl ether. The filler was first approved in 2005 for mid-to-deep dermal implantation for the correction of moderate-to-severe facial wrinkles and folds, such as nasolabial folds.

Medicis recently conducted a clinical study (MA-1399-15) to evaluate the safety and effectiveness of the filler in the augmentation of soft tissue fullness of the lips. The study included 135 patients, who received lip augmentation with Restylane, and 45 patients with no treatment. The mean volume of filler was 2.9 cc per patient, with a range of 0.6 -5.6 cc per patient. At 8 weeks, 92% of patients who received Restylane were considered responders.

Adverse events occurred in 99% of patients. Expected treatment-emergent adverse events included bruising, redness, swelling, pain, tenderness, itching, and skin exfoliation. Of note, herpes simplex virus 1 outbreaks occurred in 4% of patients. The outbreaks were determined to be associated with injection of the filler in 7 or 10 cases.

Forty percent of patients who received the filler had adverse outcomes that they felt affected their daily activity or were disabling; 15% of Restylane patients experienced adverse events (typically swelling and tenderness) that lasted more than 15 days.

The panel was particularly concerned about the implications of the treatment in younger patients who may still be growing and are likely to receive repeat treatments over time.

"My only problem with voting completely yes … is that I don't think that the question was worded in such a way that I felt totally comfortable giving my final approval for safety, efficacy, and risk/benefit ratio to all populations," said panel member Dr. Delora L. Mount, who is an associate professor of surgery and pediatrics at the University of Wisconsin in Madison.

The FDA panel was also concerned about the lack of men and individuals with dark skin in the trial. Only one man was included and 38 individuals were Fitzpatrick skin type IV, 3 individuals were type V, and none were type VI.

The FDA usually follows its panels' advice, but is not obligated to do so.

Dermatologists may not have to use Restylane off-label for lip augmentation any longer. A Food and Drug Administration panel voted 6-0 with 1 abstention that benefits outweigh risks for using the filler as a submucosal injection for lip augmentation on April 27.

The panel also voted 6-0 with 1 abstention that the filler is safe and effective for the expanded indication.

Restylane (Medicis Aesthetics) is a hyaluronic acid gel generated by Streptococcus bacteria, chemically crosslinked with 1,4 butanediol diglycidyl ether. The filler was first approved in 2005 for mid-to-deep dermal implantation for the correction of moderate-to-severe facial wrinkles and folds, such as nasolabial folds.

Medicis recently conducted a clinical study (MA-1399-15) to evaluate the safety and effectiveness of the filler in the augmentation of soft tissue fullness of the lips. The study included 135 patients, who received lip augmentation with Restylane, and 45 patients with no treatment. The mean volume of filler was 2.9 cc per patient, with a range of 0.6 -5.6 cc per patient. At 8 weeks, 92% of patients who received Restylane were considered responders.

Adverse events occurred in 99% of patients. Expected treatment-emergent adverse events included bruising, redness, swelling, pain, tenderness, itching, and skin exfoliation. Of note, herpes simplex virus 1 outbreaks occurred in 4% of patients. The outbreaks were determined to be associated with injection of the filler in 7 or 10 cases.

Forty percent of patients who received the filler had adverse outcomes that they felt affected their daily activity or were disabling; 15% of Restylane patients experienced adverse events (typically swelling and tenderness) that lasted more than 15 days.

The panel was particularly concerned about the implications of the treatment in younger patients who may still be growing and are likely to receive repeat treatments over time.

"My only problem with voting completely yes … is that I don't think that the question was worded in such a way that I felt totally comfortable giving my final approval for safety, efficacy, and risk/benefit ratio to all populations," said panel member Dr. Delora L. Mount, who is an associate professor of surgery and pediatrics at the University of Wisconsin in Madison.

The FDA panel was also concerned about the lack of men and individuals with dark skin in the trial. Only one man was included and 38 individuals were Fitzpatrick skin type IV, 3 individuals were type V, and none were type VI.

The FDA usually follows its panels' advice, but is not obligated to do so.

A program of regular tai chi exercises improved measures of quality of life in patients with chronic heart failure but failed to improve more conventional measures of exercise efficacy, compared with patients who only received education.

"Tai chi exercise, a multicomponent mind-body training modality that is safe and has good rates of adherence, may provide value in improving daily exercise, quality of life, self-efficacy, and mood in frail, deconditioned patients with systolic HF. A more restricted focus on traditional measured exercise capacity may underestimate the potential benefits of integrated interventions such as tai chi," wrote Dr. Gloria Y. Yeh and her coinvestigators in a study released April 25 in the Archives of Internal Medicine.

Photo credit: (c) Willie B. Thomas/iStockphoto.com

Tai chi is a gentle, meditative exercise of flowing circular movements, balance and weight shifting, breathing techniques, visualization, and focused internal awareness. "Tai chi may represent an additional exercise option for patients with HF because it integrates multiple relevant processes, including mild to moderate aerobic activity, upper and lower extremity training, and core strengthening," they said.

The researchers recruited 100 heart failure patients with a left ventricular ejection fraction of 40% or lower in the past 2 years, a stable medical regimen, and New York Heart Association class I-III from Boston medical practices.

They were randomly assigned to receive a 12-week tai chi exercise program or a heart health education program (attention control). All participants continued to receive usual care, noted Dr. Yeh, assistant professor of medicine at Beth Israel Deaconess and in the division for research and education in complementary and integrative medical therapies at Harvard Medical School, both in Boston, and her associates.

All assessments were performed at baseline and at 12 weeks. Patients performed a symptom-limited exercise test using a bicycle ramp protocol to determine peak oxygen uptake, a 6-minute walk test, and a Timed Up and Go functional assessment.

The researchers used the Minnesota Living with Heart Failure Questionnaire (MLHFQ) to assess disease-specific quality of life, the Profile of Mood States to assess emotional states expected to respond to clinical intervention, and the Cardiac Exercise Self-Efficacy Instrument to assess patient confidence in performing exercise-related activities.

The tai chi intervention consisted of 1-hour group classes held twice weekly for 12 weeks by certified instructors. Patients were encouraged to practice at home at least three times a week. Patients in the control group attended nurse practitioner–led education sessions twice weekly and were asked not to start tai chi during the study period.

The mean age of study participants was 67 years, the mean baseline LVEF was 29%, and the median NYHA class was II. Most patients were receiving beta-blockers (86%) and ACE inhibitors (85%).

At 12 weeks, significant improvements were seen in scores on the MLHFQ, Profile of Mood States (total mood disturbance, depression, and vigor subscales), and Cardiac Exercise Self-Efficacy Instrument in the tai chi group, compared with the heart health education group. There were no significant changes in serum biomarkers, which included B-type natriuretic peptide, catecholamines, and C-reactive protein, Dr. Yeh and her associates reported (Arch. Intern. Med. 2011;171:750-7).

Post hoc exploratory analyses pointed to subsets of patients who derived significant benefits from tai chi, compared with education only. Tai chi patients without implanted cardioverter defibrillators devices, those with NYHA class II and III symptoms, and those with a nonischemic etiology of HF improved significantly on the MLHFQ, compared with education-only patients. The researchers also found that participants with a higher baseline resting heart rate had greater improvements in the MLHFQ score in the tai chi group; there was no association in the control group.

"One of the purported mechanisms of mind-body exercises, such as tai chi, is favorable modulation of the autonomic nervous system. In our post hoc analyses, we found that, in participants with higher resting heart rates (and presumably more sympathetic nervous system ‘overdrive’), there was a greater benefit with tai chi," the investigators noted.

At the 6-month follow-up telephone contact, 34 patients in the tai chi group (68.0%) reported continued practice (including daily, weekly, and monthly). There were no adverse events related to the protocol.

Dr. Yeh and her associates reported no significant financial relationships.

A program of regular tai chi exercises improved measures of quality of life in patients with chronic heart failure but failed to improve more conventional measures of exercise efficacy, compared with patients who only received education.

"Tai chi exercise, a multicomponent mind-body training modality that is safe and has good rates of adherence, may provide value in improving daily exercise, quality of life, self-efficacy, and mood in frail, deconditioned patients with systolic HF. A more restricted focus on traditional measured exercise capacity may underestimate the potential benefits of integrated interventions such as tai chi," wrote Dr. Gloria Y. Yeh and her coinvestigators in a study released April 25 in the Archives of Internal Medicine.

Photo credit: (c) Willie B. Thomas/iStockphoto.com

Tai chi is a gentle, meditative exercise of flowing circular movements, balance and weight shifting, breathing techniques, visualization, and focused internal awareness. "Tai chi may represent an additional exercise option for patients with HF because it integrates multiple relevant processes, including mild to moderate aerobic activity, upper and lower extremity training, and core strengthening," they said.

The researchers recruited 100 heart failure patients with a left ventricular ejection fraction of 40% or lower in the past 2 years, a stable medical regimen, and New York Heart Association class I-III from Boston medical practices.

They were randomly assigned to receive a 12-week tai chi exercise program or a heart health education program (attention control). All participants continued to receive usual care, noted Dr. Yeh, assistant professor of medicine at Beth Israel Deaconess and in the division for research and education in complementary and integrative medical therapies at Harvard Medical School, both in Boston, and her associates.

All assessments were performed at baseline and at 12 weeks. Patients performed a symptom-limited exercise test using a bicycle ramp protocol to determine peak oxygen uptake, a 6-minute walk test, and a Timed Up and Go functional assessment.

The researchers used the Minnesota Living with Heart Failure Questionnaire (MLHFQ) to assess disease-specific quality of life, the Profile of Mood States to assess emotional states expected to respond to clinical intervention, and the Cardiac Exercise Self-Efficacy Instrument to assess patient confidence in performing exercise-related activities.

The tai chi intervention consisted of 1-hour group classes held twice weekly for 12 weeks by certified instructors. Patients were encouraged to practice at home at least three times a week. Patients in the control group attended nurse practitioner–led education sessions twice weekly and were asked not to start tai chi during the study period.

The mean age of study participants was 67 years, the mean baseline LVEF was 29%, and the median NYHA class was II. Most patients were receiving beta-blockers (86%) and ACE inhibitors (85%).

At 12 weeks, significant improvements were seen in scores on the MLHFQ, Profile of Mood States (total mood disturbance, depression, and vigor subscales), and Cardiac Exercise Self-Efficacy Instrument in the tai chi group, compared with the heart health education group. There were no significant changes in serum biomarkers, which included B-type natriuretic peptide, catecholamines, and C-reactive protein, Dr. Yeh and her associates reported (Arch. Intern. Med. 2011;171:750-7).

Post hoc exploratory analyses pointed to subsets of patients who derived significant benefits from tai chi, compared with education only. Tai chi patients without implanted cardioverter defibrillators devices, those with NYHA class II and III symptoms, and those with a nonischemic etiology of HF improved significantly on the MLHFQ, compared with education-only patients. The researchers also found that participants with a higher baseline resting heart rate had greater improvements in the MLHFQ score in the tai chi group; there was no association in the control group.

"One of the purported mechanisms of mind-body exercises, such as tai chi, is favorable modulation of the autonomic nervous system. In our post hoc analyses, we found that, in participants with higher resting heart rates (and presumably more sympathetic nervous system ‘overdrive’), there was a greater benefit with tai chi," the investigators noted.

At the 6-month follow-up telephone contact, 34 patients in the tai chi group (68.0%) reported continued practice (including daily, weekly, and monthly). There were no adverse events related to the protocol.

Dr. Yeh and her associates reported no significant financial relationships.

A program of regular tai chi exercises improved measures of quality of life in patients with chronic heart failure but failed to improve more conventional measures of exercise efficacy, compared with patients who only received education.

"Tai chi exercise, a multicomponent mind-body training modality that is safe and has good rates of adherence, may provide value in improving daily exercise, quality of life, self-efficacy, and mood in frail, deconditioned patients with systolic HF. A more restricted focus on traditional measured exercise capacity may underestimate the potential benefits of integrated interventions such as tai chi," wrote Dr. Gloria Y. Yeh and her coinvestigators in a study released April 25 in the Archives of Internal Medicine.

Photo credit: (c) Willie B. Thomas/iStockphoto.com

Tai chi is a gentle, meditative exercise of flowing circular movements, balance and weight shifting, breathing techniques, visualization, and focused internal awareness. "Tai chi may represent an additional exercise option for patients with HF because it integrates multiple relevant processes, including mild to moderate aerobic activity, upper and lower extremity training, and core strengthening," they said.

The researchers recruited 100 heart failure patients with a left ventricular ejection fraction of 40% or lower in the past 2 years, a stable medical regimen, and New York Heart Association class I-III from Boston medical practices.

They were randomly assigned to receive a 12-week tai chi exercise program or a heart health education program (attention control). All participants continued to receive usual care, noted Dr. Yeh, assistant professor of medicine at Beth Israel Deaconess and in the division for research and education in complementary and integrative medical therapies at Harvard Medical School, both in Boston, and her associates.

All assessments were performed at baseline and at 12 weeks. Patients performed a symptom-limited exercise test using a bicycle ramp protocol to determine peak oxygen uptake, a 6-minute walk test, and a Timed Up and Go functional assessment.

The researchers used the Minnesota Living with Heart Failure Questionnaire (MLHFQ) to assess disease-specific quality of life, the Profile of Mood States to assess emotional states expected to respond to clinical intervention, and the Cardiac Exercise Self-Efficacy Instrument to assess patient confidence in performing exercise-related activities.

The tai chi intervention consisted of 1-hour group classes held twice weekly for 12 weeks by certified instructors. Patients were encouraged to practice at home at least three times a week. Patients in the control group attended nurse practitioner–led education sessions twice weekly and were asked not to start tai chi during the study period.

The mean age of study participants was 67 years, the mean baseline LVEF was 29%, and the median NYHA class was II. Most patients were receiving beta-blockers (86%) and ACE inhibitors (85%).

At 12 weeks, significant improvements were seen in scores on the MLHFQ, Profile of Mood States (total mood disturbance, depression, and vigor subscales), and Cardiac Exercise Self-Efficacy Instrument in the tai chi group, compared with the heart health education group. There were no significant changes in serum biomarkers, which included B-type natriuretic peptide, catecholamines, and C-reactive protein, Dr. Yeh and her associates reported (Arch. Intern. Med. 2011;171:750-7).

Post hoc exploratory analyses pointed to subsets of patients who derived significant benefits from tai chi, compared with education only. Tai chi patients without implanted cardioverter defibrillators devices, those with NYHA class II and III symptoms, and those with a nonischemic etiology of HF improved significantly on the MLHFQ, compared with education-only patients. The researchers also found that participants with a higher baseline resting heart rate had greater improvements in the MLHFQ score in the tai chi group; there was no association in the control group.

"One of the purported mechanisms of mind-body exercises, such as tai chi, is favorable modulation of the autonomic nervous system. In our post hoc analyses, we found that, in participants with higher resting heart rates (and presumably more sympathetic nervous system ‘overdrive’), there was a greater benefit with tai chi," the investigators noted.

At the 6-month follow-up telephone contact, 34 patients in the tai chi group (68.0%) reported continued practice (including daily, weekly, and monthly). There were no adverse events related to the protocol.

Dr. Yeh and her associates reported no significant financial relationships.