Photo by Nina Matthews

PHILADELPHIA—Results of a single-center study suggest that, when it comes to massive transfusion in pregnancy, a 1:1 ratio of red blood cells (RBCs) to plasma is not needed to maintain adequate hemostasis.

A 2:1 ratio produces prothrombin times (PTs), activated partial thromboplastin times (PTTs), and fibrinogen levels within references ranges.

Vanessa Plasencia, MLS (ASCP)^CM, of Texas Children’s Hospital in Houston, presented these findings at the AABB Annual Meeting 2014 (abstract S43-030G).

She noted that hospital staff perform approximately 4500 to 5000 deliveries per year, and they define massive transfusion as 4 or more RBC units in 1 hour or 10 or more RBC units in 24 hours.

The hospital’s initial obstetric massive transfusion protocol was 4 units of RBCs and 4 units of plasma to be issued in a cooler. Four units of group AB thawed plasma or liquid plasma were always available.

To determine if this protocol is optimal, Plasencia and her colleagues conducted a retrospective review of patient records from April 2012 to June 2014. During this time, there were 28 cases of massive transfusion.

Two of these patients died and were excluded from the study. One, who had placental abruption, received 131 RBC units and 48 plasma units (ratio=2.7:1). The other, who had placenta percreta, received 90 RBC units and 52 plasma units (ratio=1.7:1).

The median age of the remaining 26 patients was 34 years (range, 24-44). Four of these patients had placenta accreta, 2 had placenta increta, 14 had placenta percreta, and 6 had other complications (such as placental abruption, diabetes, and risks due to advanced-age pregnancy).

A median of 12 RBC units (range, 9-20) and 9 plasma units (range, 5-19) were issued. And a median of 8 RBC units (range, 6-12) and 5 plasma units (range, 4-8) were actually transfused. That translates to RBC-to-plasma ratios of 1.4:1 (range, 1.0-2.0) and 1.7:1 (1.3-2.5), respectively.

So despite the hospital’s protocol of a 1:1 RBC-to-plasma ratio, the actual ratio of transfusion in practice was approximately 2:1, Plasencia noted. And the patients had PT, PTT, and fibrinogen values within reference ranges.

Coagulation data were collected after transfusions took place, once patients were stable. The median PT was 14.8 seconds (range, 14.1-15.2), the median PTT was 29.9 seconds (range, 27.6-33.3), and the median fibrinogen was 283 mg/dL (range, 225-325).

Because of these results, Texas Children’s Hospital decided to change its massive transfusion protocol for obstetrics to a 2:1 RBC-to-plasma ratio. Now, the hospital issues 4 units of RBCs and 2 units of plasma in its initial blood package.

Photo by Nina Matthews

PHILADELPHIA—Results of a single-center study suggest that, when it comes to massive transfusion in pregnancy, a 1:1 ratio of red blood cells (RBCs) to plasma is not needed to maintain adequate hemostasis.

A 2:1 ratio produces prothrombin times (PTs), activated partial thromboplastin times (PTTs), and fibrinogen levels within references ranges.

Vanessa Plasencia, MLS (ASCP)^CM, of Texas Children’s Hospital in Houston, presented these findings at the AABB Annual Meeting 2014 (abstract S43-030G).

She noted that hospital staff perform approximately 4500 to 5000 deliveries per year, and they define massive transfusion as 4 or more RBC units in 1 hour or 10 or more RBC units in 24 hours.

The hospital’s initial obstetric massive transfusion protocol was 4 units of RBCs and 4 units of plasma to be issued in a cooler. Four units of group AB thawed plasma or liquid plasma were always available.

To determine if this protocol is optimal, Plasencia and her colleagues conducted a retrospective review of patient records from April 2012 to June 2014. During this time, there were 28 cases of massive transfusion.

Two of these patients died and were excluded from the study. One, who had placental abruption, received 131 RBC units and 48 plasma units (ratio=2.7:1). The other, who had placenta percreta, received 90 RBC units and 52 plasma units (ratio=1.7:1).

The median age of the remaining 26 patients was 34 years (range, 24-44). Four of these patients had placenta accreta, 2 had placenta increta, 14 had placenta percreta, and 6 had other complications (such as placental abruption, diabetes, and risks due to advanced-age pregnancy).

A median of 12 RBC units (range, 9-20) and 9 plasma units (range, 5-19) were issued. And a median of 8 RBC units (range, 6-12) and 5 plasma units (range, 4-8) were actually transfused. That translates to RBC-to-plasma ratios of 1.4:1 (range, 1.0-2.0) and 1.7:1 (1.3-2.5), respectively.

So despite the hospital’s protocol of a 1:1 RBC-to-plasma ratio, the actual ratio of transfusion in practice was approximately 2:1, Plasencia noted. And the patients had PT, PTT, and fibrinogen values within reference ranges.

Coagulation data were collected after transfusions took place, once patients were stable. The median PT was 14.8 seconds (range, 14.1-15.2), the median PTT was 29.9 seconds (range, 27.6-33.3), and the median fibrinogen was 283 mg/dL (range, 225-325).

Because of these results, Texas Children’s Hospital decided to change its massive transfusion protocol for obstetrics to a 2:1 RBC-to-plasma ratio. Now, the hospital issues 4 units of RBCs and 2 units of plasma in its initial blood package.

Photo by Nina Matthews

PHILADELPHIA—Results of a single-center study suggest that, when it comes to massive transfusion in pregnancy, a 1:1 ratio of red blood cells (RBCs) to plasma is not needed to maintain adequate hemostasis.

A 2:1 ratio produces prothrombin times (PTs), activated partial thromboplastin times (PTTs), and fibrinogen levels within references ranges.

Vanessa Plasencia, MLS (ASCP)^CM, of Texas Children’s Hospital in Houston, presented these findings at the AABB Annual Meeting 2014 (abstract S43-030G).

She noted that hospital staff perform approximately 4500 to 5000 deliveries per year, and they define massive transfusion as 4 or more RBC units in 1 hour or 10 or more RBC units in 24 hours.

The hospital’s initial obstetric massive transfusion protocol was 4 units of RBCs and 4 units of plasma to be issued in a cooler. Four units of group AB thawed plasma or liquid plasma were always available.

To determine if this protocol is optimal, Plasencia and her colleagues conducted a retrospective review of patient records from April 2012 to June 2014. During this time, there were 28 cases of massive transfusion.

Two of these patients died and were excluded from the study. One, who had placental abruption, received 131 RBC units and 48 plasma units (ratio=2.7:1). The other, who had placenta percreta, received 90 RBC units and 52 plasma units (ratio=1.7:1).

The median age of the remaining 26 patients was 34 years (range, 24-44). Four of these patients had placenta accreta, 2 had placenta increta, 14 had placenta percreta, and 6 had other complications (such as placental abruption, diabetes, and risks due to advanced-age pregnancy).

A median of 12 RBC units (range, 9-20) and 9 plasma units (range, 5-19) were issued. And a median of 8 RBC units (range, 6-12) and 5 plasma units (range, 4-8) were actually transfused. That translates to RBC-to-plasma ratios of 1.4:1 (range, 1.0-2.0) and 1.7:1 (1.3-2.5), respectively.

So despite the hospital’s protocol of a 1:1 RBC-to-plasma ratio, the actual ratio of transfusion in practice was approximately 2:1, Plasencia noted. And the patients had PT, PTT, and fibrinogen values within reference ranges.

Coagulation data were collected after transfusions took place, once patients were stable. The median PT was 14.8 seconds (range, 14.1-15.2), the median PTT was 29.9 seconds (range, 27.6-33.3), and the median fibrinogen was 283 mg/dL (range, 225-325).

Because of these results, Texas Children’s Hospital decided to change its massive transfusion protocol for obstetrics to a 2:1 RBC-to-plasma ratio. Now, the hospital issues 4 units of RBCs and 2 units of plasma in its initial blood package.

BALTIMORE—Patients with clinically isolated syndrome (CIS) who received early treatment with interferon beta-1b had a more favorable outcome after 11 years than did patients who had delayed treatment, Ludwig Kappos, MD, and colleagues reported.

Patients in the early treatment arm of the Betaferon/Betaseron in Newly Emerging MS For Initial Treatment (BENEFIT) trial had a longer time to clinically definite multiple sclerosis (MS) (hazard ratio [HR], 0.67), compared with patients in the delayed treatment group. Patients who had early treatment also had a longer time to first relapse (HR, 0.655) and a lower annualized relapse rate (relative risk, 0.8094), compared with those in the delayed treatment group.

Patients in BENEFIT 11 were randomized to receive either 250 µg of interferon beta-1b as early treatment or placebo as delayed treatment subcutaneously every other day. All participants had CIS and two or more MRI lesions suggestive of MS. After two years or conversion to clinically definite MS, patients who had received placebo were offered treatment with interferon beta-1b but could take another medication or no medication for MS. In the delayed treatment group, the mean delay in start of interferon beta-1b treatment was 1.33 years.

Eleven years after the initial randomization, all patients were asked to complete a comprehensive reassessment. A total of 167 patients received early treatment with interferon beta-1b, and 111 received placebo in BENEFIT 11.

Scores on the Expanded Disability Status Scale (EDSS) “remained low and stable,” with a median of 2.0 and a median change from baseline of 0.5 in both groups, noted Dr. Kappos, Chair in Neurology at the University Hospital Basel, Switzerland. Kaplan–Meier estimates of risk of secondary progressive MS at 11 years were 4.5% in the early treatment group and 8.3% in the delayed treatment groups.

“The 11-year follow-up of the BENEFIT trial includes a sizeable proportion of the originally randomized patients from the participating centers and shows that relapse-related clinical outcomes—time to clinically definite MS, time to first relapse, and annualized relapse rate—still favor patients who had early treatment with interferon beta-1b, relative to those in the delayed interferon beta-1b treatment arm,” stated Dr. Kappos.

The differences between the treatment groups remained after 11 years “despite the relatively small differences in interferon beta-1b exposure between the treatment arms,” noted Dr. Kappos. All patients in the delayed treatment group began their treatment within a maximum of two years following a first demyelinating event.

“BENEFIT 11 provides evidence that the early treatment of patients with CIS had a positive impact on clinical outcomes, even 11 years postrandomization, and supports the importance of starting therapy with interferon beta-1b early in the course of disease,” Dr. Kappos concluded. “Disability data from BENEFIT 11 also appear to suggest a positive effect of interferon beta-1b on EDSS progression.”

Are Patients With Ischemic Stroke Receiving Guideline-Concordant Cardiac Stress Testing?
Guideline-concordant cardiac screening is underused in patients who have had an ischemic stroke without evidence of previous cardiac stress testing, researchers reported.

“Current guidelines recommend screening for coronary heart disease using cardiac stress testing for ischemic stroke patients at high risk of future cardiac events,” stated Jason J. Sico, MD, Assistant Professor of Neurology at the Yale University School of Medicine and Director of Stroke Care at the VA Connecticut Healthcare System in New Haven. “Whether high-risk stroke patients routinely receive guideline-concordant cardiac stress testing is not known.”

Dr. Sico and colleagues analyzed the medical records of 3,965 veterans from 131 Veterans Health Administration facilities who were admitted with a confirmed diagnosis of ischemic stroke in 2007. The investigators used a Framingham Risk Score of 20 or greater to define patients who had a high risk of coronary heart disease. The study authors used logistic regression analysis to assess whether cardiac stress testing had been performed more frequently among patients who were at high risk for stroke.

Among the 2,337 patients who were included in the analysis, 664 (28%) had a Framingham Risk Score of 20 or greater. A total of 140 patients (6%) had cardiac stress testing within six months of discharge.

“High-risk patients were as likely to have received cardiac stress testing as were those with a low Framingham Risk Score (odds ratio, 0.90),” Dr. Sico reported.

Mild TBI Is a More Common Risk Factor for Early-Onset Alzheimer’s Disease Than for Late-Onset Alzheimer’s Disease
Mild traumatic brain injury (TBI) occurring two or more years before the initial diagnosis of dementia is more common in patients with early-onset Alzheimer’s disease, compared with patients who have late-onset Alzheimer’s disease, according to research presented.

Ugur Sener, MD, of the Department of Neurology, University of Oklahoma Medical Center in Oklahoma City, and colleagues conducted a retrospective chart review that compared patients with early-onset Alzheimer’s disease with those who had late-onset Alzheimer’s disease, regarding vascular risk factors, depression, excessive use of alcohol, TBI, education, and family history of dementia. Neuroimaging tests and laboratory screening tests were performed according to guidelines from the American Academy of Neurology.

The investigators found that 35 patients had early-onset Alzheimer’s disease and 103 patients had late-onset Alzheimer’s disease during the study period of September 1, 2010, through September 1, 2013. Seven of the 35 patients with early-onset Alzheimer’s disease had had a concussion two years or more before their initial visit, compared with five of the 103 patients with late-onset Alzheimer’s disease.

“There were no significant differences in any of the other risk factors,” stated Dr. Sener.

Sodium Channel–Blocking AEDs Linked to Better Adherence
Patients with epilepsy who use a sodium channel–blocking antiepileptic drug (AED) have a higher likelihood of treatment adherence for 12 months, compared with patients who use AEDs with other mechanisms, researchers reported.

Jennifer S. Korsnes, Senior Health Outcomes Scientist, RTI Health Solutions in Research Triangle Park, North Carolina, and colleagues based their findings on a review of a US commercial claims database of adult patients with epilepsy, ages 18 to 65. Patients were required to have six or more months of continuous health plan enrollment before their index date and 12 or more months of continuous enrollment after their index date, as well as a monotherapy index AED. Patients were considered to be adherent if they had a proportion of days covered greater than or equal to 80% with an AED during the 12-month follow-up. The investigators performed logistic regression analysis to assess the relationship between AED mechanism and adherence.

A total of 53,338 patients were included in the study—40.2% had been taking a sodium channel blocker, 15.8% were using a gamma-aminobutyric acid (GABA) enhancer, 23.3% were using a synaptic vesicle protein 2A (SV2A) binding agent, 10.1% had been taking a glutamate blocker, and 10.6% had been using a multiple-mechanism index AED.

Compared with patients who were using a sodium-channel blocker, the one-year odds of being adherent were 57.2% lower for patients taking a GABA enhancer, 8.3% lower for patients taking an SV2A-binding agent, 6.8% lower for patients taking a glutamate blocker, and 12% lower for patients using a multiple-mechanism AED.

—Colby Stong

BALTIMORE—Patients with clinically isolated syndrome (CIS) who received early treatment with interferon beta-1b had a more favorable outcome after 11 years than did patients who had delayed treatment, Ludwig Kappos, MD, and colleagues reported.

Patients in the early treatment arm of the Betaferon/Betaseron in Newly Emerging MS For Initial Treatment (BENEFIT) trial had a longer time to clinically definite multiple sclerosis (MS) (hazard ratio [HR], 0.67), compared with patients in the delayed treatment group. Patients who had early treatment also had a longer time to first relapse (HR, 0.655) and a lower annualized relapse rate (relative risk, 0.8094), compared with those in the delayed treatment group.

Patients in BENEFIT 11 were randomized to receive either 250 µg of interferon beta-1b as early treatment or placebo as delayed treatment subcutaneously every other day. All participants had CIS and two or more MRI lesions suggestive of MS. After two years or conversion to clinically definite MS, patients who had received placebo were offered treatment with interferon beta-1b but could take another medication or no medication for MS. In the delayed treatment group, the mean delay in start of interferon beta-1b treatment was 1.33 years.

Eleven years after the initial randomization, all patients were asked to complete a comprehensive reassessment. A total of 167 patients received early treatment with interferon beta-1b, and 111 received placebo in BENEFIT 11.

Scores on the Expanded Disability Status Scale (EDSS) “remained low and stable,” with a median of 2.0 and a median change from baseline of 0.5 in both groups, noted Dr. Kappos, Chair in Neurology at the University Hospital Basel, Switzerland. Kaplan–Meier estimates of risk of secondary progressive MS at 11 years were 4.5% in the early treatment group and 8.3% in the delayed treatment groups.

“The 11-year follow-up of the BENEFIT trial includes a sizeable proportion of the originally randomized patients from the participating centers and shows that relapse-related clinical outcomes—time to clinically definite MS, time to first relapse, and annualized relapse rate—still favor patients who had early treatment with interferon beta-1b, relative to those in the delayed interferon beta-1b treatment arm,” stated Dr. Kappos.

The differences between the treatment groups remained after 11 years “despite the relatively small differences in interferon beta-1b exposure between the treatment arms,” noted Dr. Kappos. All patients in the delayed treatment group began their treatment within a maximum of two years following a first demyelinating event.

“BENEFIT 11 provides evidence that the early treatment of patients with CIS had a positive impact on clinical outcomes, even 11 years postrandomization, and supports the importance of starting therapy with interferon beta-1b early in the course of disease,” Dr. Kappos concluded. “Disability data from BENEFIT 11 also appear to suggest a positive effect of interferon beta-1b on EDSS progression.”

Are Patients With Ischemic Stroke Receiving Guideline-Concordant Cardiac Stress Testing?
Guideline-concordant cardiac screening is underused in patients who have had an ischemic stroke without evidence of previous cardiac stress testing, researchers reported.

“Current guidelines recommend screening for coronary heart disease using cardiac stress testing for ischemic stroke patients at high risk of future cardiac events,” stated Jason J. Sico, MD, Assistant Professor of Neurology at the Yale University School of Medicine and Director of Stroke Care at the VA Connecticut Healthcare System in New Haven. “Whether high-risk stroke patients routinely receive guideline-concordant cardiac stress testing is not known.”

Dr. Sico and colleagues analyzed the medical records of 3,965 veterans from 131 Veterans Health Administration facilities who were admitted with a confirmed diagnosis of ischemic stroke in 2007. The investigators used a Framingham Risk Score of 20 or greater to define patients who had a high risk of coronary heart disease. The study authors used logistic regression analysis to assess whether cardiac stress testing had been performed more frequently among patients who were at high risk for stroke.

Among the 2,337 patients who were included in the analysis, 664 (28%) had a Framingham Risk Score of 20 or greater. A total of 140 patients (6%) had cardiac stress testing within six months of discharge.

“High-risk patients were as likely to have received cardiac stress testing as were those with a low Framingham Risk Score (odds ratio, 0.90),” Dr. Sico reported.

Mild TBI Is a More Common Risk Factor for Early-Onset Alzheimer’s Disease Than for Late-Onset Alzheimer’s Disease
Mild traumatic brain injury (TBI) occurring two or more years before the initial diagnosis of dementia is more common in patients with early-onset Alzheimer’s disease, compared with patients who have late-onset Alzheimer’s disease, according to research presented.

Ugur Sener, MD, of the Department of Neurology, University of Oklahoma Medical Center in Oklahoma City, and colleagues conducted a retrospective chart review that compared patients with early-onset Alzheimer’s disease with those who had late-onset Alzheimer’s disease, regarding vascular risk factors, depression, excessive use of alcohol, TBI, education, and family history of dementia. Neuroimaging tests and laboratory screening tests were performed according to guidelines from the American Academy of Neurology.

The investigators found that 35 patients had early-onset Alzheimer’s disease and 103 patients had late-onset Alzheimer’s disease during the study period of September 1, 2010, through September 1, 2013. Seven of the 35 patients with early-onset Alzheimer’s disease had had a concussion two years or more before their initial visit, compared with five of the 103 patients with late-onset Alzheimer’s disease.

“There were no significant differences in any of the other risk factors,” stated Dr. Sener.

Sodium Channel–Blocking AEDs Linked to Better Adherence
Patients with epilepsy who use a sodium channel–blocking antiepileptic drug (AED) have a higher likelihood of treatment adherence for 12 months, compared with patients who use AEDs with other mechanisms, researchers reported.

Jennifer S. Korsnes, Senior Health Outcomes Scientist, RTI Health Solutions in Research Triangle Park, North Carolina, and colleagues based their findings on a review of a US commercial claims database of adult patients with epilepsy, ages 18 to 65. Patients were required to have six or more months of continuous health plan enrollment before their index date and 12 or more months of continuous enrollment after their index date, as well as a monotherapy index AED. Patients were considered to be adherent if they had a proportion of days covered greater than or equal to 80% with an AED during the 12-month follow-up. The investigators performed logistic regression analysis to assess the relationship between AED mechanism and adherence.

A total of 53,338 patients were included in the study—40.2% had been taking a sodium channel blocker, 15.8% were using a gamma-aminobutyric acid (GABA) enhancer, 23.3% were using a synaptic vesicle protein 2A (SV2A) binding agent, 10.1% had been taking a glutamate blocker, and 10.6% had been using a multiple-mechanism index AED.

Compared with patients who were using a sodium-channel blocker, the one-year odds of being adherent were 57.2% lower for patients taking a GABA enhancer, 8.3% lower for patients taking an SV2A-binding agent, 6.8% lower for patients taking a glutamate blocker, and 12% lower for patients using a multiple-mechanism AED.

—Colby Stong

BALTIMORE—Patients with clinically isolated syndrome (CIS) who received early treatment with interferon beta-1b had a more favorable outcome after 11 years than did patients who had delayed treatment, Ludwig Kappos, MD, and colleagues reported.

Patients in the early treatment arm of the Betaferon/Betaseron in Newly Emerging MS For Initial Treatment (BENEFIT) trial had a longer time to clinically definite multiple sclerosis (MS) (hazard ratio [HR], 0.67), compared with patients in the delayed treatment group. Patients who had early treatment also had a longer time to first relapse (HR, 0.655) and a lower annualized relapse rate (relative risk, 0.8094), compared with those in the delayed treatment group.

Patients in BENEFIT 11 were randomized to receive either 250 µg of interferon beta-1b as early treatment or placebo as delayed treatment subcutaneously every other day. All participants had CIS and two or more MRI lesions suggestive of MS. After two years or conversion to clinically definite MS, patients who had received placebo were offered treatment with interferon beta-1b but could take another medication or no medication for MS. In the delayed treatment group, the mean delay in start of interferon beta-1b treatment was 1.33 years.

Eleven years after the initial randomization, all patients were asked to complete a comprehensive reassessment. A total of 167 patients received early treatment with interferon beta-1b, and 111 received placebo in BENEFIT 11.

Scores on the Expanded Disability Status Scale (EDSS) “remained low and stable,” with a median of 2.0 and a median change from baseline of 0.5 in both groups, noted Dr. Kappos, Chair in Neurology at the University Hospital Basel, Switzerland. Kaplan–Meier estimates of risk of secondary progressive MS at 11 years were 4.5% in the early treatment group and 8.3% in the delayed treatment groups.

“The 11-year follow-up of the BENEFIT trial includes a sizeable proportion of the originally randomized patients from the participating centers and shows that relapse-related clinical outcomes—time to clinically definite MS, time to first relapse, and annualized relapse rate—still favor patients who had early treatment with interferon beta-1b, relative to those in the delayed interferon beta-1b treatment arm,” stated Dr. Kappos.

The differences between the treatment groups remained after 11 years “despite the relatively small differences in interferon beta-1b exposure between the treatment arms,” noted Dr. Kappos. All patients in the delayed treatment group began their treatment within a maximum of two years following a first demyelinating event.

“BENEFIT 11 provides evidence that the early treatment of patients with CIS had a positive impact on clinical outcomes, even 11 years postrandomization, and supports the importance of starting therapy with interferon beta-1b early in the course of disease,” Dr. Kappos concluded. “Disability data from BENEFIT 11 also appear to suggest a positive effect of interferon beta-1b on EDSS progression.”

Are Patients With Ischemic Stroke Receiving Guideline-Concordant Cardiac Stress Testing?
Guideline-concordant cardiac screening is underused in patients who have had an ischemic stroke without evidence of previous cardiac stress testing, researchers reported.

“Current guidelines recommend screening for coronary heart disease using cardiac stress testing for ischemic stroke patients at high risk of future cardiac events,” stated Jason J. Sico, MD, Assistant Professor of Neurology at the Yale University School of Medicine and Director of Stroke Care at the VA Connecticut Healthcare System in New Haven. “Whether high-risk stroke patients routinely receive guideline-concordant cardiac stress testing is not known.”

Dr. Sico and colleagues analyzed the medical records of 3,965 veterans from 131 Veterans Health Administration facilities who were admitted with a confirmed diagnosis of ischemic stroke in 2007. The investigators used a Framingham Risk Score of 20 or greater to define patients who had a high risk of coronary heart disease. The study authors used logistic regression analysis to assess whether cardiac stress testing had been performed more frequently among patients who were at high risk for stroke.

Among the 2,337 patients who were included in the analysis, 664 (28%) had a Framingham Risk Score of 20 or greater. A total of 140 patients (6%) had cardiac stress testing within six months of discharge.

“High-risk patients were as likely to have received cardiac stress testing as were those with a low Framingham Risk Score (odds ratio, 0.90),” Dr. Sico reported.

Mild TBI Is a More Common Risk Factor for Early-Onset Alzheimer’s Disease Than for Late-Onset Alzheimer’s Disease
Mild traumatic brain injury (TBI) occurring two or more years before the initial diagnosis of dementia is more common in patients with early-onset Alzheimer’s disease, compared with patients who have late-onset Alzheimer’s disease, according to research presented.

Ugur Sener, MD, of the Department of Neurology, University of Oklahoma Medical Center in Oklahoma City, and colleagues conducted a retrospective chart review that compared patients with early-onset Alzheimer’s disease with those who had late-onset Alzheimer’s disease, regarding vascular risk factors, depression, excessive use of alcohol, TBI, education, and family history of dementia. Neuroimaging tests and laboratory screening tests were performed according to guidelines from the American Academy of Neurology.

The investigators found that 35 patients had early-onset Alzheimer’s disease and 103 patients had late-onset Alzheimer’s disease during the study period of September 1, 2010, through September 1, 2013. Seven of the 35 patients with early-onset Alzheimer’s disease had had a concussion two years or more before their initial visit, compared with five of the 103 patients with late-onset Alzheimer’s disease.

“There were no significant differences in any of the other risk factors,” stated Dr. Sener.

Sodium Channel–Blocking AEDs Linked to Better Adherence
Patients with epilepsy who use a sodium channel–blocking antiepileptic drug (AED) have a higher likelihood of treatment adherence for 12 months, compared with patients who use AEDs with other mechanisms, researchers reported.

Jennifer S. Korsnes, Senior Health Outcomes Scientist, RTI Health Solutions in Research Triangle Park, North Carolina, and colleagues based their findings on a review of a US commercial claims database of adult patients with epilepsy, ages 18 to 65. Patients were required to have six or more months of continuous health plan enrollment before their index date and 12 or more months of continuous enrollment after their index date, as well as a monotherapy index AED. Patients were considered to be adherent if they had a proportion of days covered greater than or equal to 80% with an AED during the 12-month follow-up. The investigators performed logistic regression analysis to assess the relationship between AED mechanism and adherence.

A total of 53,338 patients were included in the study—40.2% had been taking a sodium channel blocker, 15.8% were using a gamma-aminobutyric acid (GABA) enhancer, 23.3% were using a synaptic vesicle protein 2A (SV2A) binding agent, 10.1% had been taking a glutamate blocker, and 10.6% had been using a multiple-mechanism index AED.

Compared with patients who were using a sodium-channel blocker, the one-year odds of being adherent were 57.2% lower for patients taking a GABA enhancer, 8.3% lower for patients taking an SV2A-binding agent, 6.8% lower for patients taking a glutamate blocker, and 12% lower for patients using a multiple-mechanism AED.

—Colby Stong

In his monthly podcast for The Journal of Community and Supportive Oncology for October, David Henry examines two research articles that focus on patient-provider communication: one article looks at patient and provider concordance on symptoms and the other discusses the informational needs and the quality of life of patients after being diagnosed with metastatic breast cancer. Two other original research articles on weight change in breast cancer patients on third-generation adjuvant chemotherapy and the quality of supportive care in patients with advanced lung cancer in the Veterans Health Administration plus a Case Report about breast cancer with brain metastases in pregnancy round off the clinical portion of the line-up. A feature article details the current state of biomarker development and challenges that temper their clinical potential.

In his monthly podcast for The Journal of Community and Supportive Oncology for October, David Henry examines two research articles that focus on patient-provider communication: one article looks at patient and provider concordance on symptoms and the other discusses the informational needs and the quality of life of patients after being diagnosed with metastatic breast cancer. Two other original research articles on weight change in breast cancer patients on third-generation adjuvant chemotherapy and the quality of supportive care in patients with advanced lung cancer in the Veterans Health Administration plus a Case Report about breast cancer with brain metastases in pregnancy round off the clinical portion of the line-up. A feature article details the current state of biomarker development and challenges that temper their clinical potential.

In his monthly podcast for The Journal of Community and Supportive Oncology for October, David Henry examines two research articles that focus on patient-provider communication: one article looks at patient and provider concordance on symptoms and the other discusses the informational needs and the quality of life of patients after being diagnosed with metastatic breast cancer. Two other original research articles on weight change in breast cancer patients on third-generation adjuvant chemotherapy and the quality of supportive care in patients with advanced lung cancer in the Veterans Health Administration plus a Case Report about breast cancer with brain metastases in pregnancy round off the clinical portion of the line-up. A feature article details the current state of biomarker development and challenges that temper their clinical potential.

RELIZEN: NONHORMONAL TX FOR HOT FLASHES
RELIZEN^® is a patented, nonhormonal therapy for the relief of hot flashes associated with menopause from JDS Therapeutics.New to the United States, Relizen has been used by women and physicians in Europe for more than 15 years, according to the manufacturer, and has clinical efficacy data established in a placebo-controlled trial published in Climacteric. The active ingredient is a non-estrogenic, purified Swedish pollen extract that has pollen allergens removed. The daily dose is 2 pills/day.
FOR MORE INFORMATION, VISIT www.relizen.com

RISK ASSESSMENT FOR SPORADIC BREAST CA
BREVAGenplus, from Phenogen Sciences, Inc, assesses clinical risk factors (Gail score) and genetic markers (SNP profile) to determine 5-year and lifetime risks of developing sporadic (nonhereditary) breast cancer. The test is for Caucasian, Hispanic, and African-American women, aged 35 years and older, who have not had breast cancer but have one or more risk factors for developing breast cancer.
FOR MORE INFORMATION, VISIT http://phenogensciences.com

3 NEW DEVICE LENGTHS FOR DISSECTION
Covidien has added 13-cm, 26-cm, and 48-cm lengths to its Sonicision^tm Cordless Ultrasonic Dissection Device portfolio. Covidien reports that Sonicision offers surgeons faster dissection with increased mobility without having to manage electrical cords. Single-use and reusable components available.
FOR MORE INFORMATION, VISIT www.covidien.com

ROBOTICS SIMULATOR
Simbionix has launched RobotiX Mentor, a comprehensive educational tool for surgeons of all levels to practice the skills required to perform robotic surgery. By using basic task modules and cross-specialty clinical procedure simulations, surgeons can experience partial or entire robotic procedures.
FOR MORE INFORMATION, VISIT www.simbionix.com

NATURAL PRODUCTS FOR PREGNANCY
Fairhaven Health’s PregnancyPlus Line includes Prenatal Vitamins, Omega-3, and Cal-Mag (calcium, magnesium, and vitamin D3) natural supplements. Fairhaven Health claims that the Belly Rest Pregnancy Pillow provides back-pain relief during sleep. All products are BPA-free, with no artificial flavors, colors, or preservatives.
FOR MORE INFORMATION, VISIT www.fairhavenhealth.com

OPTIMIZE OFFICE WORKFLOW
Comtron offers Medgen EHR, a customized electronic health record (EHR) system. Comtron claims the Medgen EHR system is easily adaptable and is cost-effective by offering increased efficiency, decreased overhead, and improved patient care.
FOR MORE INFORMATION, VISIT www.medgenehr.com

VISUALIZATION ENHANCEMENT TOOLS
Karl Storz launched the Image1^® SPIES^tm visualization enhancement modular system for endoscopic surgery. SPIES, an acronym for Storz Professional Image Enhancement System, has three components: video software, a modular camera control unit, and a graphic user interface. Karl Storz reports that the modular design allows customization to individual needs. The combined camera heads and visualization tools offer homogenous illumination and contrast enhancement.
FOR MORE INFORMATION, VISIT www.karlstorz.com

NONINVASIVE PRENATAL GENETIC BLOOD TEST
Synapse Diagnostics offers Materni T21 PLUS, a test for specific chromosomal conditions in a fetus that are associated with birth defects. Conducted on blood drawn from the mother as early as 10 weeks’ gestation, the test uses genomic sequencing. Synapse Diagnostics claims that this is the only test that not only detects abnormalities like Down syndrome but also reveals defects called “microdeletions” caused by a missing gene that are otherwise difficult to discover early in pregnancy.
FOR MORE INFORMATION, VISIT www.synapsediagnostics.com

NEW ULTRASOUND SYSTEM
Samsung Electronics America, Inc. has introduced the UGEO WS80A ultrasound system for ObGyn applications. Key features: 21.5"-wide LED monitor with touch panel, 5D technologies, FRV^tm (Feto Realistic View) with 3D visualization, and piezoelectric crystal design for high resolution. Samsung reports that the UGEO WS80A has improved gray scale and color with a more precise signal, speckle reduction, and edge and contrast enhancement.
FOR MORE INFORMATION, VISIT www.samsung.com/healthcare

SEAL & CUT TECHNOLOGY
Aesculap has expanded its line of Caiman 5 Seal and Cut Technology to include 24-cm and 44-cm lengths of vessel sealing devices in addition to its original 36-cm device. Aesculap claims that the extended jaw design provides uniform pressure distribution across a variety of tissue thicknesses. These bipolar electrosurgical RF energy instruments are intended for open and laparoscopic surgery.
FOR MORE INFORMATION, VISIT www.caimansurgery.com

DETECTING RUPTURED MEMBRANES
ROM Plus^®is a rapid qualitative test for in vitro detection of amniotic proteins in vaginal secretions of pregnant women for possible diagnosis of premature rupture of membranes (PROM). ROM Plus uses a monoclonal/polyclonal antibody approach to detect two amniotic proteins, AFP and PP12. Accurate and prompt diagnosis of PROM helps decrease or avoid serious complications for mother and fetus.
FOR MORE INFORMATION, VISIT www.clinicalinnovations.com

RELIZEN: NONHORMONAL TX FOR HOT FLASHES
RELIZEN^® is a patented, nonhormonal therapy for the relief of hot flashes associated with menopause from JDS Therapeutics.New to the United States, Relizen has been used by women and physicians in Europe for more than 15 years, according to the manufacturer, and has clinical efficacy data established in a placebo-controlled trial published in Climacteric. The active ingredient is a non-estrogenic, purified Swedish pollen extract that has pollen allergens removed. The daily dose is 2 pills/day.
FOR MORE INFORMATION, VISIT www.relizen.com

RISK ASSESSMENT FOR SPORADIC BREAST CA
BREVAGenplus, from Phenogen Sciences, Inc, assesses clinical risk factors (Gail score) and genetic markers (SNP profile) to determine 5-year and lifetime risks of developing sporadic (nonhereditary) breast cancer. The test is for Caucasian, Hispanic, and African-American women, aged 35 years and older, who have not had breast cancer but have one or more risk factors for developing breast cancer.
FOR MORE INFORMATION, VISIT http://phenogensciences.com

3 NEW DEVICE LENGTHS FOR DISSECTION
Covidien has added 13-cm, 26-cm, and 48-cm lengths to its Sonicision^tm Cordless Ultrasonic Dissection Device portfolio. Covidien reports that Sonicision offers surgeons faster dissection with increased mobility without having to manage electrical cords. Single-use and reusable components available.
FOR MORE INFORMATION, VISIT www.covidien.com

ROBOTICS SIMULATOR
Simbionix has launched RobotiX Mentor, a comprehensive educational tool for surgeons of all levels to practice the skills required to perform robotic surgery. By using basic task modules and cross-specialty clinical procedure simulations, surgeons can experience partial or entire robotic procedures.
FOR MORE INFORMATION, VISIT www.simbionix.com

NATURAL PRODUCTS FOR PREGNANCY
Fairhaven Health’s PregnancyPlus Line includes Prenatal Vitamins, Omega-3, and Cal-Mag (calcium, magnesium, and vitamin D3) natural supplements. Fairhaven Health claims that the Belly Rest Pregnancy Pillow provides back-pain relief during sleep. All products are BPA-free, with no artificial flavors, colors, or preservatives.
FOR MORE INFORMATION, VISIT www.fairhavenhealth.com

OPTIMIZE OFFICE WORKFLOW
Comtron offers Medgen EHR, a customized electronic health record (EHR) system. Comtron claims the Medgen EHR system is easily adaptable and is cost-effective by offering increased efficiency, decreased overhead, and improved patient care.
FOR MORE INFORMATION, VISIT www.medgenehr.com

VISUALIZATION ENHANCEMENT TOOLS
Karl Storz launched the Image1^® SPIES^tm visualization enhancement modular system for endoscopic surgery. SPIES, an acronym for Storz Professional Image Enhancement System, has three components: video software, a modular camera control unit, and a graphic user interface. Karl Storz reports that the modular design allows customization to individual needs. The combined camera heads and visualization tools offer homogenous illumination and contrast enhancement.
FOR MORE INFORMATION, VISIT www.karlstorz.com

NONINVASIVE PRENATAL GENETIC BLOOD TEST
Synapse Diagnostics offers Materni T21 PLUS, a test for specific chromosomal conditions in a fetus that are associated with birth defects. Conducted on blood drawn from the mother as early as 10 weeks’ gestation, the test uses genomic sequencing. Synapse Diagnostics claims that this is the only test that not only detects abnormalities like Down syndrome but also reveals defects called “microdeletions” caused by a missing gene that are otherwise difficult to discover early in pregnancy.
FOR MORE INFORMATION, VISIT www.synapsediagnostics.com

NEW ULTRASOUND SYSTEM
Samsung Electronics America, Inc. has introduced the UGEO WS80A ultrasound system for ObGyn applications. Key features: 21.5"-wide LED monitor with touch panel, 5D technologies, FRV^tm (Feto Realistic View) with 3D visualization, and piezoelectric crystal design for high resolution. Samsung reports that the UGEO WS80A has improved gray scale and color with a more precise signal, speckle reduction, and edge and contrast enhancement.
FOR MORE INFORMATION, VISIT www.samsung.com/healthcare

SEAL & CUT TECHNOLOGY
Aesculap has expanded its line of Caiman 5 Seal and Cut Technology to include 24-cm and 44-cm lengths of vessel sealing devices in addition to its original 36-cm device. Aesculap claims that the extended jaw design provides uniform pressure distribution across a variety of tissue thicknesses. These bipolar electrosurgical RF energy instruments are intended for open and laparoscopic surgery.
FOR MORE INFORMATION, VISIT www.caimansurgery.com

DETECTING RUPTURED MEMBRANES
ROM Plus^®is a rapid qualitative test for in vitro detection of amniotic proteins in vaginal secretions of pregnant women for possible diagnosis of premature rupture of membranes (PROM). ROM Plus uses a monoclonal/polyclonal antibody approach to detect two amniotic proteins, AFP and PP12. Accurate and prompt diagnosis of PROM helps decrease or avoid serious complications for mother and fetus.
FOR MORE INFORMATION, VISIT www.clinicalinnovations.com

RELIZEN: NONHORMONAL TX FOR HOT FLASHES
RELIZEN^® is a patented, nonhormonal therapy for the relief of hot flashes associated with menopause from JDS Therapeutics.New to the United States, Relizen has been used by women and physicians in Europe for more than 15 years, according to the manufacturer, and has clinical efficacy data established in a placebo-controlled trial published in Climacteric. The active ingredient is a non-estrogenic, purified Swedish pollen extract that has pollen allergens removed. The daily dose is 2 pills/day.
FOR MORE INFORMATION, VISIT www.relizen.com

RISK ASSESSMENT FOR SPORADIC BREAST CA
BREVAGenplus, from Phenogen Sciences, Inc, assesses clinical risk factors (Gail score) and genetic markers (SNP profile) to determine 5-year and lifetime risks of developing sporadic (nonhereditary) breast cancer. The test is for Caucasian, Hispanic, and African-American women, aged 35 years and older, who have not had breast cancer but have one or more risk factors for developing breast cancer.
FOR MORE INFORMATION, VISIT http://phenogensciences.com

3 NEW DEVICE LENGTHS FOR DISSECTION
Covidien has added 13-cm, 26-cm, and 48-cm lengths to its Sonicision^tm Cordless Ultrasonic Dissection Device portfolio. Covidien reports that Sonicision offers surgeons faster dissection with increased mobility without having to manage electrical cords. Single-use and reusable components available.
FOR MORE INFORMATION, VISIT www.covidien.com

ROBOTICS SIMULATOR
Simbionix has launched RobotiX Mentor, a comprehensive educational tool for surgeons of all levels to practice the skills required to perform robotic surgery. By using basic task modules and cross-specialty clinical procedure simulations, surgeons can experience partial or entire robotic procedures.
FOR MORE INFORMATION, VISIT www.simbionix.com

NATURAL PRODUCTS FOR PREGNANCY
Fairhaven Health’s PregnancyPlus Line includes Prenatal Vitamins, Omega-3, and Cal-Mag (calcium, magnesium, and vitamin D3) natural supplements. Fairhaven Health claims that the Belly Rest Pregnancy Pillow provides back-pain relief during sleep. All products are BPA-free, with no artificial flavors, colors, or preservatives.
FOR MORE INFORMATION, VISIT www.fairhavenhealth.com

OPTIMIZE OFFICE WORKFLOW
Comtron offers Medgen EHR, a customized electronic health record (EHR) system. Comtron claims the Medgen EHR system is easily adaptable and is cost-effective by offering increased efficiency, decreased overhead, and improved patient care.
FOR MORE INFORMATION, VISIT www.medgenehr.com

VISUALIZATION ENHANCEMENT TOOLS
Karl Storz launched the Image1^® SPIES^tm visualization enhancement modular system for endoscopic surgery. SPIES, an acronym for Storz Professional Image Enhancement System, has three components: video software, a modular camera control unit, and a graphic user interface. Karl Storz reports that the modular design allows customization to individual needs. The combined camera heads and visualization tools offer homogenous illumination and contrast enhancement.
FOR MORE INFORMATION, VISIT www.karlstorz.com

NONINVASIVE PRENATAL GENETIC BLOOD TEST
Synapse Diagnostics offers Materni T21 PLUS, a test for specific chromosomal conditions in a fetus that are associated with birth defects. Conducted on blood drawn from the mother as early as 10 weeks’ gestation, the test uses genomic sequencing. Synapse Diagnostics claims that this is the only test that not only detects abnormalities like Down syndrome but also reveals defects called “microdeletions” caused by a missing gene that are otherwise difficult to discover early in pregnancy.
FOR MORE INFORMATION, VISIT www.synapsediagnostics.com

NEW ULTRASOUND SYSTEM
Samsung Electronics America, Inc. has introduced the UGEO WS80A ultrasound system for ObGyn applications. Key features: 21.5"-wide LED monitor with touch panel, 5D technologies, FRV^tm (Feto Realistic View) with 3D visualization, and piezoelectric crystal design for high resolution. Samsung reports that the UGEO WS80A has improved gray scale and color with a more precise signal, speckle reduction, and edge and contrast enhancement.
FOR MORE INFORMATION, VISIT www.samsung.com/healthcare

SEAL & CUT TECHNOLOGY
Aesculap has expanded its line of Caiman 5 Seal and Cut Technology to include 24-cm and 44-cm lengths of vessel sealing devices in addition to its original 36-cm device. Aesculap claims that the extended jaw design provides uniform pressure distribution across a variety of tissue thicknesses. These bipolar electrosurgical RF energy instruments are intended for open and laparoscopic surgery.
FOR MORE INFORMATION, VISIT www.caimansurgery.com

DETECTING RUPTURED MEMBRANES
ROM Plus^®is a rapid qualitative test for in vitro detection of amniotic proteins in vaginal secretions of pregnant women for possible diagnosis of premature rupture of membranes (PROM). ROM Plus uses a monoclonal/polyclonal antibody approach to detect two amniotic proteins, AFP and PP12. Accurate and prompt diagnosis of PROM helps decrease or avoid serious complications for mother and fetus.
FOR MORE INFORMATION, VISIT www.clinicalinnovations.com

COLUMBUS, OHIO—Cognitive impairment at age 12 months predicts a subsequent diagnosis of autism spectrum disorder in children with tuberous sclerosis complex, according to researchers.

The relationship between intellectual disability and social-communication deficits among children with tuberous sclerosis complex, however, requires further investigation, said the investigators.

Shafali S. Jeste, MD, Assistant Professor in Psychiatry and Neurology at the University of California, Los Angeles, and colleagues conducted a longitudinal cohort study of infants with tuberous sclerosis complex to determine early clinical predictors of autism spectrum disorder and characterize the phenotype of autism in young children with tuberous sclerosis complex.

The researchers recruited infants with tuberous sclerosis complex and typically developing infants as young as 3 months and followed them longitudinally until age 36 months. They gathered data including standard cognitive and social-communication measures (ie, Mullen Scales of Early Learning, Autism Observation Scale of Infancy, and the Early Social Communication Scales), comorbidities questionnaires, and a detailed seizure history. Autism spectrum diagnosis was made using the Autism Diagnostic Observation Schedule and confirmed using best clinical estimate at ages 18, 24, and 36 months.

Of a population of 40 infants, 22 received a diagnosis of autism spectrum disorder. Children with autism had significantly greater cognitive delays by age 12 months and a significant decline in nonverbal IQ from ages 12 to 36 months, compared with children without autism. At 24 months, children with autism had significantly greater cognitive impairment, higher anxiety symptoms, more sleep impairment, and a trend toward greater seizure severity. Children not diagnosed with autism had subclinical evidence of social-communication impairment, particularly in language and play.

Do rTMS and Constraint Therapy Reduce Perinatal Stroke Hemiparesis?
Children with hemiparesis resulting from perinatal stroke perceive marked increases in goal-specific function following treatment with repetitive transcranial magnetic stimulation (rTMS) and constraint therapy, investigators reported.

Further study of noninvasive brain stimulation is feasible and may enhance motor learning therapy in such patients, according to the researchers.

Researchers previously had studied rTMS and constraint therapy in adults with stroke, but the treatments had not been examined in perinatal stroke. Adam Kirton, MD, Associate Professor of Pediatrics and Clinical Neurosciences at the University of Calgary in Canada, and colleagues conducted a blinded factorial trial of rTMS and constraint therapy in 45 children with perinatal stroke hemiparesis. Eligible participants were between ages 6 and 18, and the sample’s mean age was 11.

The children were randomized to daily inhibitory rTMS (ie, 1,200 stimulations at 1 Hz) over contralesional M1, constraint therapy, both treatments, or neither treatment. All interventions were administered for two weeks as part of a goal-directed, peer-supported motor learning camp.

The study’s primary outcome measure was the Canadian Occupational Performance Measure (COPM) at one, eight, and 24 weeks. Secondary outcomes included Assisting Hand Assessment (AHA), Melbourne Assessment (MA), safety, and tolerability. The researchers assessed change across treatment groups from baseline to six months and across all time points.

For all participants, COPM performance and satisfaction scores increased, and maximal gains were observed at six months. Linear mixed effects model analysis demonstrated effects of combined rTMS and constraint therapy on AHA gains at all time points. Constraint therapy alone increased AHA at two months, rTMS alone increased AHA at one week, and neither treatment decreased normal hand function. Affected hand function did not decrease with rTMS in children with ipsilateral corticospinal tract arrangements. The procedures were well tolerated.

Arbaclofen May Not Reduce Social Avoidance in Fragile X Syndrome
Arbaclofen may not reduce social avoidance among patients with fragile X syndrome, according to clinical trial results presented. The drug may modify the disease’s trajectory, however, and deserves further testing, said Elizabeth Berry-Kravis, MD, PhD.

Arbaclofen is a specific GABA-B agonist that has been approved to treat spasticity in multiple sclerosis. The drug improved several abnormal phenotypes in animal models of fragile X syndrome and showed promise in a phase II clinical trial. Dr. Berry-Kravis, Associate Professor of Biochemistry, Neurological Sciences, and Pediatrics at Rush Medical College in Chicago, and colleagues conducted two phase III placebo-controlled trials to determine the drug’s safety and efficacy for social avoidance in fragile X syndrome.

The investigators randomized 125 patients to arbaclofen or placebo in a flexible-dose trial. Eligible patients were between ages 12 and 50. In a separate fixed-dose trial, the researchers randomized 172 participants to 5 mg of arbaclofen twice per day, 10 mg of arbaclofen twice per day, 10 mg of arbaclofen three times per day, or placebo. Eligible subjects in this trial were between ages 5 and 11.

The primary end point for both trials was the Fragile X Syndrome Social Avoidance subscale of the Aberrant Behavior Checklist (ABC). Secondary outcomes included other ABC subscale scores, Clinical Global Impression–Improvement score, Clinical Global Impression-Severity score, and Vineland Socialization domain score.

The investigators observed no serious adverse events during the trial. The most common adverse events included headache, vomiting, nausea, irritability, anxiety, hyperactivity, decreased appetite, and infections. In all, 12 patients discontinued participation in the trial because of neurobehavioral adverse events.

The flexible-dose trial did not indicate a benefit for arbaclofen over placebo for any outcome. The highest dose group in the fixed-dose trial had significantly better outcome than those who received placebo on the ABC Fragile X Irritability subscale. The same group demonstrated a trend toward benefit on the ABC Fragile X Social Avoidance and Hyperactivity subscales.

“Data from secondary measures and the long-term treatment extension (improved Vineland Socialization [domain score]) suggest that some patients derive benefit, but these studies illustrate the challenges of translating targeted treatments from animal models to humans in fragile X syndrome,” said Dr. Berry-Kravis.

Everolimus Reduces SEGA Volume in Tuberous Sclerosis Complex
Everolimus, an mTOR inhibitor, significantly reduces the volume of subependymal giant cell astrocytoma (SEGA) in children with tuberous sclerosis complex, according to an extension analysis presented. In a phase III trial, the researchers did not find any new safety concerns to be associated with the drug.

David N. Franz, MD, Pediatric Neurologist at Cincinnati Children’s Hospital Medical Center, and colleagues enrolled 117 patients in a randomized, double-blind trial of everolimus. All patients had SEGA associated with tuberous sclerosis complex of at least 1 cm in diameter. Participants received either 4.5 mg/m2/day of oral everolimus or placebo. The primary end point was SEGA response rate, which the investigators defined as the proportion of patients with 50% or greater reduction in SEGA volume, compared with baseline.

Patients’ mean age was approximately 11, and mean SEGA volume was 2.6 cm³. Participants received treatment for a median of 41 months.

At the original cutoff of the trial, SEGA response rate was 34.6% for everolimus and 0.0% for placebo. At that point, patients on placebo were offered open-label everolimus in the extension phase of the trial. As of January 11, 2013, 111 patients had received at least one dose of everolimus and were included in the extension analysis. The overall SEGA response rate was 48.6%, and the SEGA response rate for everolimus increased steadily until week 96. The duration of SEGA response ranged from 2.1 to 31.1 months.

Adverse events were common, but their incidence decreased with time. Approximately 40% of patients had serious adverse events, and 19% were suspected to be associated with everolimus. The most frequent serious adverse events occurring in more than 3% of patients were pneumonia, pyrexia, gastroenteritis, and convulsion.

—Erik Greb

COLUMBUS, OHIO—Cognitive impairment at age 12 months predicts a subsequent diagnosis of autism spectrum disorder in children with tuberous sclerosis complex, according to researchers.

The relationship between intellectual disability and social-communication deficits among children with tuberous sclerosis complex, however, requires further investigation, said the investigators.

Shafali S. Jeste, MD, Assistant Professor in Psychiatry and Neurology at the University of California, Los Angeles, and colleagues conducted a longitudinal cohort study of infants with tuberous sclerosis complex to determine early clinical predictors of autism spectrum disorder and characterize the phenotype of autism in young children with tuberous sclerosis complex.

The researchers recruited infants with tuberous sclerosis complex and typically developing infants as young as 3 months and followed them longitudinally until age 36 months. They gathered data including standard cognitive and social-communication measures (ie, Mullen Scales of Early Learning, Autism Observation Scale of Infancy, and the Early Social Communication Scales), comorbidities questionnaires, and a detailed seizure history. Autism spectrum diagnosis was made using the Autism Diagnostic Observation Schedule and confirmed using best clinical estimate at ages 18, 24, and 36 months.

Of a population of 40 infants, 22 received a diagnosis of autism spectrum disorder. Children with autism had significantly greater cognitive delays by age 12 months and a significant decline in nonverbal IQ from ages 12 to 36 months, compared with children without autism. At 24 months, children with autism had significantly greater cognitive impairment, higher anxiety symptoms, more sleep impairment, and a trend toward greater seizure severity. Children not diagnosed with autism had subclinical evidence of social-communication impairment, particularly in language and play.

Do rTMS and Constraint Therapy Reduce Perinatal Stroke Hemiparesis?
Children with hemiparesis resulting from perinatal stroke perceive marked increases in goal-specific function following treatment with repetitive transcranial magnetic stimulation (rTMS) and constraint therapy, investigators reported.

Further study of noninvasive brain stimulation is feasible and may enhance motor learning therapy in such patients, according to the researchers.

Researchers previously had studied rTMS and constraint therapy in adults with stroke, but the treatments had not been examined in perinatal stroke. Adam Kirton, MD, Associate Professor of Pediatrics and Clinical Neurosciences at the University of Calgary in Canada, and colleagues conducted a blinded factorial trial of rTMS and constraint therapy in 45 children with perinatal stroke hemiparesis. Eligible participants were between ages 6 and 18, and the sample’s mean age was 11.

The children were randomized to daily inhibitory rTMS (ie, 1,200 stimulations at 1 Hz) over contralesional M1, constraint therapy, both treatments, or neither treatment. All interventions were administered for two weeks as part of a goal-directed, peer-supported motor learning camp.

The study’s primary outcome measure was the Canadian Occupational Performance Measure (COPM) at one, eight, and 24 weeks. Secondary outcomes included Assisting Hand Assessment (AHA), Melbourne Assessment (MA), safety, and tolerability. The researchers assessed change across treatment groups from baseline to six months and across all time points.

For all participants, COPM performance and satisfaction scores increased, and maximal gains were observed at six months. Linear mixed effects model analysis demonstrated effects of combined rTMS and constraint therapy on AHA gains at all time points. Constraint therapy alone increased AHA at two months, rTMS alone increased AHA at one week, and neither treatment decreased normal hand function. Affected hand function did not decrease with rTMS in children with ipsilateral corticospinal tract arrangements. The procedures were well tolerated.

Arbaclofen May Not Reduce Social Avoidance in Fragile X Syndrome
Arbaclofen may not reduce social avoidance among patients with fragile X syndrome, according to clinical trial results presented. The drug may modify the disease’s trajectory, however, and deserves further testing, said Elizabeth Berry-Kravis, MD, PhD.

Arbaclofen is a specific GABA-B agonist that has been approved to treat spasticity in multiple sclerosis. The drug improved several abnormal phenotypes in animal models of fragile X syndrome and showed promise in a phase II clinical trial. Dr. Berry-Kravis, Associate Professor of Biochemistry, Neurological Sciences, and Pediatrics at Rush Medical College in Chicago, and colleagues conducted two phase III placebo-controlled trials to determine the drug’s safety and efficacy for social avoidance in fragile X syndrome.

The investigators randomized 125 patients to arbaclofen or placebo in a flexible-dose trial. Eligible patients were between ages 12 and 50. In a separate fixed-dose trial, the researchers randomized 172 participants to 5 mg of arbaclofen twice per day, 10 mg of arbaclofen twice per day, 10 mg of arbaclofen three times per day, or placebo. Eligible subjects in this trial were between ages 5 and 11.

The primary end point for both trials was the Fragile X Syndrome Social Avoidance subscale of the Aberrant Behavior Checklist (ABC). Secondary outcomes included other ABC subscale scores, Clinical Global Impression–Improvement score, Clinical Global Impression-Severity score, and Vineland Socialization domain score.

The investigators observed no serious adverse events during the trial. The most common adverse events included headache, vomiting, nausea, irritability, anxiety, hyperactivity, decreased appetite, and infections. In all, 12 patients discontinued participation in the trial because of neurobehavioral adverse events.

The flexible-dose trial did not indicate a benefit for arbaclofen over placebo for any outcome. The highest dose group in the fixed-dose trial had significantly better outcome than those who received placebo on the ABC Fragile X Irritability subscale. The same group demonstrated a trend toward benefit on the ABC Fragile X Social Avoidance and Hyperactivity subscales.

“Data from secondary measures and the long-term treatment extension (improved Vineland Socialization [domain score]) suggest that some patients derive benefit, but these studies illustrate the challenges of translating targeted treatments from animal models to humans in fragile X syndrome,” said Dr. Berry-Kravis.

Everolimus Reduces SEGA Volume in Tuberous Sclerosis Complex
Everolimus, an mTOR inhibitor, significantly reduces the volume of subependymal giant cell astrocytoma (SEGA) in children with tuberous sclerosis complex, according to an extension analysis presented. In a phase III trial, the researchers did not find any new safety concerns to be associated with the drug.

David N. Franz, MD, Pediatric Neurologist at Cincinnati Children’s Hospital Medical Center, and colleagues enrolled 117 patients in a randomized, double-blind trial of everolimus. All patients had SEGA associated with tuberous sclerosis complex of at least 1 cm in diameter. Participants received either 4.5 mg/m2/day of oral everolimus or placebo. The primary end point was SEGA response rate, which the investigators defined as the proportion of patients with 50% or greater reduction in SEGA volume, compared with baseline.

Patients’ mean age was approximately 11, and mean SEGA volume was 2.6 cm³. Participants received treatment for a median of 41 months.

At the original cutoff of the trial, SEGA response rate was 34.6% for everolimus and 0.0% for placebo. At that point, patients on placebo were offered open-label everolimus in the extension phase of the trial. As of January 11, 2013, 111 patients had received at least one dose of everolimus and were included in the extension analysis. The overall SEGA response rate was 48.6%, and the SEGA response rate for everolimus increased steadily until week 96. The duration of SEGA response ranged from 2.1 to 31.1 months.

Adverse events were common, but their incidence decreased with time. Approximately 40% of patients had serious adverse events, and 19% were suspected to be associated with everolimus. The most frequent serious adverse events occurring in more than 3% of patients were pneumonia, pyrexia, gastroenteritis, and convulsion.

—Erik Greb

COLUMBUS, OHIO—Cognitive impairment at age 12 months predicts a subsequent diagnosis of autism spectrum disorder in children with tuberous sclerosis complex, according to researchers.

The relationship between intellectual disability and social-communication deficits among children with tuberous sclerosis complex, however, requires further investigation, said the investigators.

Shafali S. Jeste, MD, Assistant Professor in Psychiatry and Neurology at the University of California, Los Angeles, and colleagues conducted a longitudinal cohort study of infants with tuberous sclerosis complex to determine early clinical predictors of autism spectrum disorder and characterize the phenotype of autism in young children with tuberous sclerosis complex.

The researchers recruited infants with tuberous sclerosis complex and typically developing infants as young as 3 months and followed them longitudinally until age 36 months. They gathered data including standard cognitive and social-communication measures (ie, Mullen Scales of Early Learning, Autism Observation Scale of Infancy, and the Early Social Communication Scales), comorbidities questionnaires, and a detailed seizure history. Autism spectrum diagnosis was made using the Autism Diagnostic Observation Schedule and confirmed using best clinical estimate at ages 18, 24, and 36 months.

Of a population of 40 infants, 22 received a diagnosis of autism spectrum disorder. Children with autism had significantly greater cognitive delays by age 12 months and a significant decline in nonverbal IQ from ages 12 to 36 months, compared with children without autism. At 24 months, children with autism had significantly greater cognitive impairment, higher anxiety symptoms, more sleep impairment, and a trend toward greater seizure severity. Children not diagnosed with autism had subclinical evidence of social-communication impairment, particularly in language and play.

Do rTMS and Constraint Therapy Reduce Perinatal Stroke Hemiparesis?
Children with hemiparesis resulting from perinatal stroke perceive marked increases in goal-specific function following treatment with repetitive transcranial magnetic stimulation (rTMS) and constraint therapy, investigators reported.

Further study of noninvasive brain stimulation is feasible and may enhance motor learning therapy in such patients, according to the researchers.

Researchers previously had studied rTMS and constraint therapy in adults with stroke, but the treatments had not been examined in perinatal stroke. Adam Kirton, MD, Associate Professor of Pediatrics and Clinical Neurosciences at the University of Calgary in Canada, and colleagues conducted a blinded factorial trial of rTMS and constraint therapy in 45 children with perinatal stroke hemiparesis. Eligible participants were between ages 6 and 18, and the sample’s mean age was 11.

The children were randomized to daily inhibitory rTMS (ie, 1,200 stimulations at 1 Hz) over contralesional M1, constraint therapy, both treatments, or neither treatment. All interventions were administered for two weeks as part of a goal-directed, peer-supported motor learning camp.

The study’s primary outcome measure was the Canadian Occupational Performance Measure (COPM) at one, eight, and 24 weeks. Secondary outcomes included Assisting Hand Assessment (AHA), Melbourne Assessment (MA), safety, and tolerability. The researchers assessed change across treatment groups from baseline to six months and across all time points.

For all participants, COPM performance and satisfaction scores increased, and maximal gains were observed at six months. Linear mixed effects model analysis demonstrated effects of combined rTMS and constraint therapy on AHA gains at all time points. Constraint therapy alone increased AHA at two months, rTMS alone increased AHA at one week, and neither treatment decreased normal hand function. Affected hand function did not decrease with rTMS in children with ipsilateral corticospinal tract arrangements. The procedures were well tolerated.

Arbaclofen May Not Reduce Social Avoidance in Fragile X Syndrome
Arbaclofen may not reduce social avoidance among patients with fragile X syndrome, according to clinical trial results presented. The drug may modify the disease’s trajectory, however, and deserves further testing, said Elizabeth Berry-Kravis, MD, PhD.

Arbaclofen is a specific GABA-B agonist that has been approved to treat spasticity in multiple sclerosis. The drug improved several abnormal phenotypes in animal models of fragile X syndrome and showed promise in a phase II clinical trial. Dr. Berry-Kravis, Associate Professor of Biochemistry, Neurological Sciences, and Pediatrics at Rush Medical College in Chicago, and colleagues conducted two phase III placebo-controlled trials to determine the drug’s safety and efficacy for social avoidance in fragile X syndrome.

The investigators randomized 125 patients to arbaclofen or placebo in a flexible-dose trial. Eligible patients were between ages 12 and 50. In a separate fixed-dose trial, the researchers randomized 172 participants to 5 mg of arbaclofen twice per day, 10 mg of arbaclofen twice per day, 10 mg of arbaclofen three times per day, or placebo. Eligible subjects in this trial were between ages 5 and 11.

The primary end point for both trials was the Fragile X Syndrome Social Avoidance subscale of the Aberrant Behavior Checklist (ABC). Secondary outcomes included other ABC subscale scores, Clinical Global Impression–Improvement score, Clinical Global Impression-Severity score, and Vineland Socialization domain score.

The investigators observed no serious adverse events during the trial. The most common adverse events included headache, vomiting, nausea, irritability, anxiety, hyperactivity, decreased appetite, and infections. In all, 12 patients discontinued participation in the trial because of neurobehavioral adverse events.

The flexible-dose trial did not indicate a benefit for arbaclofen over placebo for any outcome. The highest dose group in the fixed-dose trial had significantly better outcome than those who received placebo on the ABC Fragile X Irritability subscale. The same group demonstrated a trend toward benefit on the ABC Fragile X Social Avoidance and Hyperactivity subscales.

“Data from secondary measures and the long-term treatment extension (improved Vineland Socialization [domain score]) suggest that some patients derive benefit, but these studies illustrate the challenges of translating targeted treatments from animal models to humans in fragile X syndrome,” said Dr. Berry-Kravis.

Everolimus Reduces SEGA Volume in Tuberous Sclerosis Complex
Everolimus, an mTOR inhibitor, significantly reduces the volume of subependymal giant cell astrocytoma (SEGA) in children with tuberous sclerosis complex, according to an extension analysis presented. In a phase III trial, the researchers did not find any new safety concerns to be associated with the drug.

David N. Franz, MD, Pediatric Neurologist at Cincinnati Children’s Hospital Medical Center, and colleagues enrolled 117 patients in a randomized, double-blind trial of everolimus. All patients had SEGA associated with tuberous sclerosis complex of at least 1 cm in diameter. Participants received either 4.5 mg/m2/day of oral everolimus or placebo. The primary end point was SEGA response rate, which the investigators defined as the proportion of patients with 50% or greater reduction in SEGA volume, compared with baseline.

Patients’ mean age was approximately 11, and mean SEGA volume was 2.6 cm³. Participants received treatment for a median of 41 months.

At the original cutoff of the trial, SEGA response rate was 34.6% for everolimus and 0.0% for placebo. At that point, patients on placebo were offered open-label everolimus in the extension phase of the trial. As of January 11, 2013, 111 patients had received at least one dose of everolimus and were included in the extension analysis. The overall SEGA response rate was 48.6%, and the SEGA response rate for everolimus increased steadily until week 96. The duration of SEGA response ranged from 2.1 to 31.1 months.

Adverse events were common, but their incidence decreased with time. Approximately 40% of patients had serious adverse events, and 19% were suspected to be associated with everolimus. The most frequent serious adverse events occurring in more than 3% of patients were pneumonia, pyrexia, gastroenteritis, and convulsion.

—Erik Greb

SAN DIEGO – Only 1% of families that filled out psychosocial screening questionnaires during medical appointments later sought free mental health consultations, the same rate as for families that were not screened, investigators reported.

“Unless large controlled trials are able to show a process and an outcome benefit, it may be preferable to invest in providing mental health treatment” instead of screening, concluded lead investigator Brianna J. Lewis of the Mount Sinai School of Medicine, New York, and her associates. The researchers presented the findings at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

The study was a post-hoc analysis of data on 3,143 patient encounters at a pediatric allergy clinic in New York City between March and September 2013. Two to five days a week, the investigators had asked children aged 8 years and older and their parents to fill out one-page questionnaires about problems such as distress, anxiety, bullying, and quality-of-life issues. They did not screen patients on the other days, “creating a naturalistic opportunity to compare between screened and nonscreened cohorts,” they added. Because screening was part of regular care, participants did not need to provide informed consent, which eliminated the possibility of selection bias, the researchers said.

In all, 6.1% of families who underwent screening were referred to a mental health consultation, but only 1% followed up, even though consults were offered for free and without third-party billing, the researchers said. The follow-up rate also was 1% for the 1,972 families that were not screened. Among the families who pursued a follow-up consult, 56% of the screened group and 67% of the unscreened group received a psychiatric diagnosis (P = 0.26), Ms. Lewis and her associates reported.

Past studies by the investigators showed that screening children and adults during medical care appointments is “hard to justify,” they noted.

The Jaffe Family Foundation, Pine/Segal Family, and Vanech Family Foundation supported the research. The investigators declared no conflicts of interest.

SAN DIEGO – Only 1% of families that filled out psychosocial screening questionnaires during medical appointments later sought free mental health consultations, the same rate as for families that were not screened, investigators reported.

“Unless large controlled trials are able to show a process and an outcome benefit, it may be preferable to invest in providing mental health treatment” instead of screening, concluded lead investigator Brianna J. Lewis of the Mount Sinai School of Medicine, New York, and her associates. The researchers presented the findings at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

The study was a post-hoc analysis of data on 3,143 patient encounters at a pediatric allergy clinic in New York City between March and September 2013. Two to five days a week, the investigators had asked children aged 8 years and older and their parents to fill out one-page questionnaires about problems such as distress, anxiety, bullying, and quality-of-life issues. They did not screen patients on the other days, “creating a naturalistic opportunity to compare between screened and nonscreened cohorts,” they added. Because screening was part of regular care, participants did not need to provide informed consent, which eliminated the possibility of selection bias, the researchers said.

In all, 6.1% of families who underwent screening were referred to a mental health consultation, but only 1% followed up, even though consults were offered for free and without third-party billing, the researchers said. The follow-up rate also was 1% for the 1,972 families that were not screened. Among the families who pursued a follow-up consult, 56% of the screened group and 67% of the unscreened group received a psychiatric diagnosis (P = 0.26), Ms. Lewis and her associates reported.

Past studies by the investigators showed that screening children and adults during medical care appointments is “hard to justify,” they noted.

The Jaffe Family Foundation, Pine/Segal Family, and Vanech Family Foundation supported the research. The investigators declared no conflicts of interest.

SAN DIEGO – Only 1% of families that filled out psychosocial screening questionnaires during medical appointments later sought free mental health consultations, the same rate as for families that were not screened, investigators reported.

“Unless large controlled trials are able to show a process and an outcome benefit, it may be preferable to invest in providing mental health treatment” instead of screening, concluded lead investigator Brianna J. Lewis of the Mount Sinai School of Medicine, New York, and her associates. The researchers presented the findings at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

The study was a post-hoc analysis of data on 3,143 patient encounters at a pediatric allergy clinic in New York City between March and September 2013. Two to five days a week, the investigators had asked children aged 8 years and older and their parents to fill out one-page questionnaires about problems such as distress, anxiety, bullying, and quality-of-life issues. They did not screen patients on the other days, “creating a naturalistic opportunity to compare between screened and nonscreened cohorts,” they added. Because screening was part of regular care, participants did not need to provide informed consent, which eliminated the possibility of selection bias, the researchers said.

In all, 6.1% of families who underwent screening were referred to a mental health consultation, but only 1% followed up, even though consults were offered for free and without third-party billing, the researchers said. The follow-up rate also was 1% for the 1,972 families that were not screened. Among the families who pursued a follow-up consult, 56% of the screened group and 67% of the unscreened group received a psychiatric diagnosis (P = 0.26), Ms. Lewis and her associates reported.

Past studies by the investigators showed that screening children and adults during medical care appointments is “hard to justify,” they noted.

The Jaffe Family Foundation, Pine/Segal Family, and Vanech Family Foundation supported the research. The investigators declared no conflicts of interest.

Paul G. Richardson, MD

NEW YORK—Calling the synergy with the proteasome inhibitor “profound,” Paul G. Richardson, MD, presented results on the combination of the pan deacetylase inhibitor panobinostat with bortezomib and dexamethasone in relapsed/refractory multiple myeloma (MM).

The phase 3 PANORAMA 1 study confirmed data from the phase 1 and 2 trials, in which the triple combination demonstrated durable responses, even in bortezomib-refractory disease.

Dr Richardson, of the Dana-Farber Cancer Institute in Boston, presented updated data from the PANORAMA 1 trial, which received an award for the most clinically relevant myeloma abstract at the Lymphoma & Myeloma 2014 congress, held October 23–25.

Investigators randomized 768 patients with relapsed or relapsed and refractory MM to receive either panobinostat (n=387) or placebo (n=381) with bortezomib and dexamethasone. Bortezomib-refractory patients were excluded.

The study was conducted in 2 treatment phases, and patients with clinical benefit at the end of the first 24-week phase could proceed to the second treatment phase, consisting of four 42-day cycles.

The primary endpoint was progression-free survival (PFS) according to modified European Society for Blood and Marrow Transplantation criteria.

The key secondary endpoint was overall survival, and additional secondary endpoints included overall response rate, complete response/near complete response, duration of response, time to response, time to progression, quality of life, and safety.

Dr Richardson pointed out that in the first treatment phase, bortezomib was administered twice a week at 1.3 mg/m² intravenously, and, in the second phase, it was given once a week. The panobinostat dose was 20 mg orally 3 times a week, and oral dexamethasone was given at 20 mg on the same day and the day after bortezomib administration.

Patients were a median age of 63 years, and nearly half (48.4%) had received 2 or more prior therapies, including bortezomib, at 43.7% in the panobinostat arm and 42.3% in the placebo arm. Half the patients had prior exposure to thalidomide, and 1 in 4 patients had received bortezomib and an immunomodulator.

Approximately two-thirds of the patients had relapsed MM, and one-third had relapsed and refractory disease.

Twenty-six percent of patients in either arm completed treatment. Forty-four percent of patients in the panobinostat arm and 50% in the placebo arm entered treatment phase 2.

The dose intensity of panobinostat decreased to 78.2% at cycle 3 and remained stable through the rest of the trial. By cycle 3, the majority of patients were receiving 15 mg of panobinostat.

Results

The 3-drug combination met its primary endpoint, with a clinically relevant increase in median PFS of 3.9 months (P<0.0001).

The benefit with panobinostat was maintained regardless of prior treatment history or baseline characteristics.

“There was benefit across all subgroups,” Dr Richardson said, “but especially in the poor-risk group.”

He noted that the overall survival curve was holding between the 2 arms at about a 3-month difference.

And the complete response/near complete response rate in the panobinostat arm was nearly double that of the control arm, at 27.6% and 15.7%, respectively (P=0.00006).

While not significant, there were clinically meaningful improvements in overall response rate, duration of response, and time to progression. The overall response rate with panobinostat was 34.5%, the clinical benefit rate 52.7%, and the median PFS 5.4 months.

Safety

“Overall, side effects were relatively low,” Dr Richardson said, the major ones consisting of hematologic laboratory abnormalities.

Almost 98% of the patients receiving panobinostat and 83.5% of those in the placebo arm had thrombocytopenia of any grade. And 1.6% of patients on panobinostat discontinued due to thrombocytopenia, compared with 0.5% in the control arm.

Dr Richardson said the thrombocytopenia was reversible and not cumulative. Platelet levels rebounded to baseline by day 1 of each cycle.

Lymphopenia, neutropenia, and anemia were also more frequent in the panobinostat arm.

Nonhematologic adverse events, particularly diarrhea and fatigue, were, for the most part, increased over control, with 4.5% of patients on the panobinostat arm discontinuing due to diarrhea and 2.9% discontinuing due to fatigue.

The incidence of adverse events was lower in the second treatment phase, when bortezomib was administered once a week.

And deaths related to study drug were very low, Dr Richardson said, with 11 in the panobinostat arm and 7 in the control arm.

The triple drug combination is “a very important concept going forward,” Dr Richardson said.

Other combinations and additional histone deacetylase inhibitors are being evaluated for MM.

Paul G. Richardson, MD

NEW YORK—Calling the synergy with the proteasome inhibitor “profound,” Paul G. Richardson, MD, presented results on the combination of the pan deacetylase inhibitor panobinostat with bortezomib and dexamethasone in relapsed/refractory multiple myeloma (MM).

The phase 3 PANORAMA 1 study confirmed data from the phase 1 and 2 trials, in which the triple combination demonstrated durable responses, even in bortezomib-refractory disease.

Dr Richardson, of the Dana-Farber Cancer Institute in Boston, presented updated data from the PANORAMA 1 trial, which received an award for the most clinically relevant myeloma abstract at the Lymphoma & Myeloma 2014 congress, held October 23–25.

Investigators randomized 768 patients with relapsed or relapsed and refractory MM to receive either panobinostat (n=387) or placebo (n=381) with bortezomib and dexamethasone. Bortezomib-refractory patients were excluded.

The study was conducted in 2 treatment phases, and patients with clinical benefit at the end of the first 24-week phase could proceed to the second treatment phase, consisting of four 42-day cycles.

The primary endpoint was progression-free survival (PFS) according to modified European Society for Blood and Marrow Transplantation criteria.

The key secondary endpoint was overall survival, and additional secondary endpoints included overall response rate, complete response/near complete response, duration of response, time to response, time to progression, quality of life, and safety.

Dr Richardson pointed out that in the first treatment phase, bortezomib was administered twice a week at 1.3 mg/m² intravenously, and, in the second phase, it was given once a week. The panobinostat dose was 20 mg orally 3 times a week, and oral dexamethasone was given at 20 mg on the same day and the day after bortezomib administration.

Patients were a median age of 63 years, and nearly half (48.4%) had received 2 or more prior therapies, including bortezomib, at 43.7% in the panobinostat arm and 42.3% in the placebo arm. Half the patients had prior exposure to thalidomide, and 1 in 4 patients had received bortezomib and an immunomodulator.

Approximately two-thirds of the patients had relapsed MM, and one-third had relapsed and refractory disease.

Twenty-six percent of patients in either arm completed treatment. Forty-four percent of patients in the panobinostat arm and 50% in the placebo arm entered treatment phase 2.

The dose intensity of panobinostat decreased to 78.2% at cycle 3 and remained stable through the rest of the trial. By cycle 3, the majority of patients were receiving 15 mg of panobinostat.

Results

The 3-drug combination met its primary endpoint, with a clinically relevant increase in median PFS of 3.9 months (P<0.0001).

The benefit with panobinostat was maintained regardless of prior treatment history or baseline characteristics.

“There was benefit across all subgroups,” Dr Richardson said, “but especially in the poor-risk group.”

He noted that the overall survival curve was holding between the 2 arms at about a 3-month difference.

And the complete response/near complete response rate in the panobinostat arm was nearly double that of the control arm, at 27.6% and 15.7%, respectively (P=0.00006).

While not significant, there were clinically meaningful improvements in overall response rate, duration of response, and time to progression. The overall response rate with panobinostat was 34.5%, the clinical benefit rate 52.7%, and the median PFS 5.4 months.

Safety

“Overall, side effects were relatively low,” Dr Richardson said, the major ones consisting of hematologic laboratory abnormalities.

Almost 98% of the patients receiving panobinostat and 83.5% of those in the placebo arm had thrombocytopenia of any grade. And 1.6% of patients on panobinostat discontinued due to thrombocytopenia, compared with 0.5% in the control arm.

Dr Richardson said the thrombocytopenia was reversible and not cumulative. Platelet levels rebounded to baseline by day 1 of each cycle.

Lymphopenia, neutropenia, and anemia were also more frequent in the panobinostat arm.

Nonhematologic adverse events, particularly diarrhea and fatigue, were, for the most part, increased over control, with 4.5% of patients on the panobinostat arm discontinuing due to diarrhea and 2.9% discontinuing due to fatigue.

The incidence of adverse events was lower in the second treatment phase, when bortezomib was administered once a week.

And deaths related to study drug were very low, Dr Richardson said, with 11 in the panobinostat arm and 7 in the control arm.

The triple drug combination is “a very important concept going forward,” Dr Richardson said.

Other combinations and additional histone deacetylase inhibitors are being evaluated for MM.

Paul G. Richardson, MD

NEW YORK—Calling the synergy with the proteasome inhibitor “profound,” Paul G. Richardson, MD, presented results on the combination of the pan deacetylase inhibitor panobinostat with bortezomib and dexamethasone in relapsed/refractory multiple myeloma (MM).

The phase 3 PANORAMA 1 study confirmed data from the phase 1 and 2 trials, in which the triple combination demonstrated durable responses, even in bortezomib-refractory disease.

Dr Richardson, of the Dana-Farber Cancer Institute in Boston, presented updated data from the PANORAMA 1 trial, which received an award for the most clinically relevant myeloma abstract at the Lymphoma & Myeloma 2014 congress, held October 23–25.

Investigators randomized 768 patients with relapsed or relapsed and refractory MM to receive either panobinostat (n=387) or placebo (n=381) with bortezomib and dexamethasone. Bortezomib-refractory patients were excluded.

The study was conducted in 2 treatment phases, and patients with clinical benefit at the end of the first 24-week phase could proceed to the second treatment phase, consisting of four 42-day cycles.

The primary endpoint was progression-free survival (PFS) according to modified European Society for Blood and Marrow Transplantation criteria.

The key secondary endpoint was overall survival, and additional secondary endpoints included overall response rate, complete response/near complete response, duration of response, time to response, time to progression, quality of life, and safety.

Dr Richardson pointed out that in the first treatment phase, bortezomib was administered twice a week at 1.3 mg/m² intravenously, and, in the second phase, it was given once a week. The panobinostat dose was 20 mg orally 3 times a week, and oral dexamethasone was given at 20 mg on the same day and the day after bortezomib administration.

Patients were a median age of 63 years, and nearly half (48.4%) had received 2 or more prior therapies, including bortezomib, at 43.7% in the panobinostat arm and 42.3% in the placebo arm. Half the patients had prior exposure to thalidomide, and 1 in 4 patients had received bortezomib and an immunomodulator.

Approximately two-thirds of the patients had relapsed MM, and one-third had relapsed and refractory disease.

Twenty-six percent of patients in either arm completed treatment. Forty-four percent of patients in the panobinostat arm and 50% in the placebo arm entered treatment phase 2.

The dose intensity of panobinostat decreased to 78.2% at cycle 3 and remained stable through the rest of the trial. By cycle 3, the majority of patients were receiving 15 mg of panobinostat.

Results

The 3-drug combination met its primary endpoint, with a clinically relevant increase in median PFS of 3.9 months (P<0.0001).

The benefit with panobinostat was maintained regardless of prior treatment history or baseline characteristics.

“There was benefit across all subgroups,” Dr Richardson said, “but especially in the poor-risk group.”

He noted that the overall survival curve was holding between the 2 arms at about a 3-month difference.

And the complete response/near complete response rate in the panobinostat arm was nearly double that of the control arm, at 27.6% and 15.7%, respectively (P=0.00006).

While not significant, there were clinically meaningful improvements in overall response rate, duration of response, and time to progression. The overall response rate with panobinostat was 34.5%, the clinical benefit rate 52.7%, and the median PFS 5.4 months.

Safety

“Overall, side effects were relatively low,” Dr Richardson said, the major ones consisting of hematologic laboratory abnormalities.

Almost 98% of the patients receiving panobinostat and 83.5% of those in the placebo arm had thrombocytopenia of any grade. And 1.6% of patients on panobinostat discontinued due to thrombocytopenia, compared with 0.5% in the control arm.

Dr Richardson said the thrombocytopenia was reversible and not cumulative. Platelet levels rebounded to baseline by day 1 of each cycle.

Lymphopenia, neutropenia, and anemia were also more frequent in the panobinostat arm.

Nonhematologic adverse events, particularly diarrhea and fatigue, were, for the most part, increased over control, with 4.5% of patients on the panobinostat arm discontinuing due to diarrhea and 2.9% discontinuing due to fatigue.

The incidence of adverse events was lower in the second treatment phase, when bortezomib was administered once a week.

And deaths related to study drug were very low, Dr Richardson said, with 11 in the panobinostat arm and 7 in the control arm.

The triple drug combination is “a very important concept going forward,” Dr Richardson said.

Other combinations and additional histone deacetylase inhibitors are being evaluated for MM.

Cord blood donation

Credit: NHS

Single and double cord blood transplants produce similar outcomes, according to a study of young patients with hematologic disorders.

Researchers found that rates of overall and disease-free survival were not significantly different in patients who received a single unit of cord blood and those who received two units.

Other outcome measures, such as neutrophil recovery, relapse, and transplant-related death, were similar between the two groups as well.

However, patients who received a single cord blood unit showed improved platelet recovery, a lower incidence of grade 3-4 acute graft-vs-host disease (GVHD), and a lower rate of extensive chronic GVHD.

John Wagner, Jr, MD, of the University of Minnesota in Minneapolis, and his colleagues reported these results in NEJM. Dr Wagner previously presented results from this study at ASH 2012.

“Based on promising early studies using two cord blood units in adults for whom one unit is often not sufficient, we designed this study in order to determine if the higher number of blood-forming stem cells in two cord blood units might improve survival,” Dr Wagner said. “What we found, however, was that both treatment arms performed very well, with similar rates of white blood cell recovery and survival.”

The researchers enrolled 224 patients, ages 1 to 21 years, with hematologic disorders, including acute and chronic leukemias as well as myelodysplastic syndromes.

Patients were randomized to receive double-unit (n=111) or single-unit (n=113) cord blood transplants after a uniform myeloablative conditioning regimen and immunoprophylaxis for GVHD.

The researchers matched the treatment arms for age, sex, self-reported race, performance status, degree of donor-recipient HLA matching, disease type, and disease status at transplant.

Survival and relapse

The study’s primary endpoint was 1-year survival, which was 65% in the double-unit arm and 73% in the single-unit arm (P=0.17). In a multivariate analysis, the risk of death did not differ significantly between the arms (hazard ratio=1.34, P=0.20).

Similarly, there was no significant difference in 1-year disease-free survival between the double- and single-unit arms—64% and 70%, respectively (P=0.11). In a multivariate analysis, the risk of relapse or death did not differ significantly between arms (hazard ratio=1.48, P=0.08).

It therefore follows that rates of relapse and transplant-related death were similar at 1 year as well. The incidence of relapse was 14% in the double-unit arm and 12% in the single-unit arm (P=0.12). And rates of transplant-related death were 22% and 19%, respectively (P=0.43).

Recovery and GVHD

The incidence of neutrophil recovery was similar between treatment arms—88% in the double-unit arm and 89% in the single-unit arm (P=0.29) at a median of 23 days (range, 11 to 133) and 21 days (range, 11 to 62) after transplant, respectively.

However, the rate of platelet recovery was significantly higher in the single-unit arm—76% vs 65% (P=0.04). Furthermore, the median time to platelet recovery was 58 days (range, 28 to 295) in the single-unit arm and 84 days (range, 22 to 716) in the double-unit arm.

The rate of grade 2-4 acute GVHD was similar between the treatment arms (P=0.78), but patients in the double-unit arm had a higher incidence of grade 3-4 acute GVHD—23% vs 13% (P=0.02).

There was no difference in the incidence of any chronic GVHD at 1 year after transplant—32% in the double-unit arm and 30% in the single-unit arm (P=0.51). But there was a higher incidence of extensive chronic GVHD after double-unit transplant—15% vs 9% (P=0.05).

“This is helpful news for physicians considering the best treatment options for their patients,” said Joanne Kurtzberg, MD, of Duke University Medical Center in Durham, North Carolina.

“We found children who have a cord blood unit with an adequate number of cells do not benefit from receiving two units. This reduces the cost of a cord blood transplant for the majority of pediatric patients needing the procedure. However, for larger children without an adequately dosed single cord blood unit, using two units will provide access to a potentially life-saving transplant.”

Cord blood donation

Credit: NHS

Single and double cord blood transplants produce similar outcomes, according to a study of young patients with hematologic disorders.

Researchers found that rates of overall and disease-free survival were not significantly different in patients who received a single unit of cord blood and those who received two units.

Other outcome measures, such as neutrophil recovery, relapse, and transplant-related death, were similar between the two groups as well.

However, patients who received a single cord blood unit showed improved platelet recovery, a lower incidence of grade 3-4 acute graft-vs-host disease (GVHD), and a lower rate of extensive chronic GVHD.

John Wagner, Jr, MD, of the University of Minnesota in Minneapolis, and his colleagues reported these results in NEJM. Dr Wagner previously presented results from this study at ASH 2012.

“Based on promising early studies using two cord blood units in adults for whom one unit is often not sufficient, we designed this study in order to determine if the higher number of blood-forming stem cells in two cord blood units might improve survival,” Dr Wagner said. “What we found, however, was that both treatment arms performed very well, with similar rates of white blood cell recovery and survival.”

The researchers enrolled 224 patients, ages 1 to 21 years, with hematologic disorders, including acute and chronic leukemias as well as myelodysplastic syndromes.

Patients were randomized to receive double-unit (n=111) or single-unit (n=113) cord blood transplants after a uniform myeloablative conditioning regimen and immunoprophylaxis for GVHD.

The researchers matched the treatment arms for age, sex, self-reported race, performance status, degree of donor-recipient HLA matching, disease type, and disease status at transplant.

Survival and relapse

The study’s primary endpoint was 1-year survival, which was 65% in the double-unit arm and 73% in the single-unit arm (P=0.17). In a multivariate analysis, the risk of death did not differ significantly between the arms (hazard ratio=1.34, P=0.20).

Similarly, there was no significant difference in 1-year disease-free survival between the double- and single-unit arms—64% and 70%, respectively (P=0.11). In a multivariate analysis, the risk of relapse or death did not differ significantly between arms (hazard ratio=1.48, P=0.08).

It therefore follows that rates of relapse and transplant-related death were similar at 1 year as well. The incidence of relapse was 14% in the double-unit arm and 12% in the single-unit arm (P=0.12). And rates of transplant-related death were 22% and 19%, respectively (P=0.43).

Recovery and GVHD

The incidence of neutrophil recovery was similar between treatment arms—88% in the double-unit arm and 89% in the single-unit arm (P=0.29) at a median of 23 days (range, 11 to 133) and 21 days (range, 11 to 62) after transplant, respectively.

However, the rate of platelet recovery was significantly higher in the single-unit arm—76% vs 65% (P=0.04). Furthermore, the median time to platelet recovery was 58 days (range, 28 to 295) in the single-unit arm and 84 days (range, 22 to 716) in the double-unit arm.

The rate of grade 2-4 acute GVHD was similar between the treatment arms (P=0.78), but patients in the double-unit arm had a higher incidence of grade 3-4 acute GVHD—23% vs 13% (P=0.02).

There was no difference in the incidence of any chronic GVHD at 1 year after transplant—32% in the double-unit arm and 30% in the single-unit arm (P=0.51). But there was a higher incidence of extensive chronic GVHD after double-unit transplant—15% vs 9% (P=0.05).

“This is helpful news for physicians considering the best treatment options for their patients,” said Joanne Kurtzberg, MD, of Duke University Medical Center in Durham, North Carolina.

“We found children who have a cord blood unit with an adequate number of cells do not benefit from receiving two units. This reduces the cost of a cord blood transplant for the majority of pediatric patients needing the procedure. However, for larger children without an adequately dosed single cord blood unit, using two units will provide access to a potentially life-saving transplant.”

Cord blood donation

Credit: NHS

Single and double cord blood transplants produce similar outcomes, according to a study of young patients with hematologic disorders.

Researchers found that rates of overall and disease-free survival were not significantly different in patients who received a single unit of cord blood and those who received two units.

Other outcome measures, such as neutrophil recovery, relapse, and transplant-related death, were similar between the two groups as well.

However, patients who received a single cord blood unit showed improved platelet recovery, a lower incidence of grade 3-4 acute graft-vs-host disease (GVHD), and a lower rate of extensive chronic GVHD.

John Wagner, Jr, MD, of the University of Minnesota in Minneapolis, and his colleagues reported these results in NEJM. Dr Wagner previously presented results from this study at ASH 2012.

“Based on promising early studies using two cord blood units in adults for whom one unit is often not sufficient, we designed this study in order to determine if the higher number of blood-forming stem cells in two cord blood units might improve survival,” Dr Wagner said. “What we found, however, was that both treatment arms performed very well, with similar rates of white blood cell recovery and survival.”

The researchers enrolled 224 patients, ages 1 to 21 years, with hematologic disorders, including acute and chronic leukemias as well as myelodysplastic syndromes.

Patients were randomized to receive double-unit (n=111) or single-unit (n=113) cord blood transplants after a uniform myeloablative conditioning regimen and immunoprophylaxis for GVHD.

The researchers matched the treatment arms for age, sex, self-reported race, performance status, degree of donor-recipient HLA matching, disease type, and disease status at transplant.

Survival and relapse

The study’s primary endpoint was 1-year survival, which was 65% in the double-unit arm and 73% in the single-unit arm (P=0.17). In a multivariate analysis, the risk of death did not differ significantly between the arms (hazard ratio=1.34, P=0.20).

Similarly, there was no significant difference in 1-year disease-free survival between the double- and single-unit arms—64% and 70%, respectively (P=0.11). In a multivariate analysis, the risk of relapse or death did not differ significantly between arms (hazard ratio=1.48, P=0.08).

It therefore follows that rates of relapse and transplant-related death were similar at 1 year as well. The incidence of relapse was 14% in the double-unit arm and 12% in the single-unit arm (P=0.12). And rates of transplant-related death were 22% and 19%, respectively (P=0.43).

Recovery and GVHD

The incidence of neutrophil recovery was similar between treatment arms—88% in the double-unit arm and 89% in the single-unit arm (P=0.29) at a median of 23 days (range, 11 to 133) and 21 days (range, 11 to 62) after transplant, respectively.

However, the rate of platelet recovery was significantly higher in the single-unit arm—76% vs 65% (P=0.04). Furthermore, the median time to platelet recovery was 58 days (range, 28 to 295) in the single-unit arm and 84 days (range, 22 to 716) in the double-unit arm.

The rate of grade 2-4 acute GVHD was similar between the treatment arms (P=0.78), but patients in the double-unit arm had a higher incidence of grade 3-4 acute GVHD—23% vs 13% (P=0.02).

There was no difference in the incidence of any chronic GVHD at 1 year after transplant—32% in the double-unit arm and 30% in the single-unit arm (P=0.51). But there was a higher incidence of extensive chronic GVHD after double-unit transplant—15% vs 9% (P=0.05).

“This is helpful news for physicians considering the best treatment options for their patients,” said Joanne Kurtzberg, MD, of Duke University Medical Center in Durham, North Carolina.

“We found children who have a cord blood unit with an adequate number of cells do not benefit from receiving two units. This reduces the cost of a cord blood transplant for the majority of pediatric patients needing the procedure. However, for larger children without an adequately dosed single cord blood unit, using two units will provide access to a potentially life-saving transplant.”

Vials of drug

Credit: Bill Branson

The US Food and Drug Administration (FDA) has granted orphan designation for a human alpha-1 antitrypsin (AAT) product known as Glassia to treat graft-vs-host disease (GVHD).

Orphan drug designation carries multiple benefits, including the availability of grant money, certain tax credits, and 7 years of market exclusivity, as well as the possibility of an expedited regulatory process.

Glassia is the first available ready-to-infuse liquid alpha1-proteinase inhibitor.

The product is already approved by the FDA to treat adults with clinically evident emphysema due to severe congenital AAT deficiency. Glassia is given intravenously once a week to augment the levels of AAT, a protein derived from human plasma, in the blood.

In recent years, researchers have discovered that AAT has anti-inflammatory, tissue protective, immunomodulatory, and anti-apoptotic properties in direct or indirect consequence of its underlying antiprotease capabilities.

These properties may attenuate inflammation by lowering levels of proinflammatory mediators such as cytokines, chemokines, and proteases that are associated with GVHD.

Preliminary human and animal studies indicate that Glassia may be able to treat and reduce the severity of GVHD occurring after allogeneic stem cell transplant.

Researchers are now evaluating Glassia in a phase 1/2 study of 24 GVHD patients with inadequate responses to steroid treatment following allogeneic stem cell transplant. The patients are enrolled in 4 dose cohorts, in which they receive up to 8 doses of Glassia. Interim data from this study is expected by the end of this year.

“Results from this phase 1/2 study in GVHD may support global clinical development activities and may serve as a platform to apply for an expansion of the AAT indications to include general organ transplantation, based on a similar mechanism of action,“ said David Tsur, Co-founder and Chief Executive Officer of Kamada, makers of Glassia.

“GVHD is a disease of significant unmet medical need, and both the disease and current therapy options carry considerable side effects. Given the favorable safety profile of Glassia, there is a strong rationale to support the development of this new indication and an increased likelihood of it becoming an effective therapy for this potentially life-threatening disease.”

“We will pursue discussion with the US and European regulators with regard to our development pathway and with an aim to move forward with a more advanced study of Glassia to treat GVHD.”

For more information on Glassia, see the full prescribing information.

Vials of drug

Credit: Bill Branson

The US Food and Drug Administration (FDA) has granted orphan designation for a human alpha-1 antitrypsin (AAT) product known as Glassia to treat graft-vs-host disease (GVHD).

Orphan drug designation carries multiple benefits, including the availability of grant money, certain tax credits, and 7 years of market exclusivity, as well as the possibility of an expedited regulatory process.

Glassia is the first available ready-to-infuse liquid alpha1-proteinase inhibitor.

The product is already approved by the FDA to treat adults with clinically evident emphysema due to severe congenital AAT deficiency. Glassia is given intravenously once a week to augment the levels of AAT, a protein derived from human plasma, in the blood.

In recent years, researchers have discovered that AAT has anti-inflammatory, tissue protective, immunomodulatory, and anti-apoptotic properties in direct or indirect consequence of its underlying antiprotease capabilities.

These properties may attenuate inflammation by lowering levels of proinflammatory mediators such as cytokines, chemokines, and proteases that are associated with GVHD.

Preliminary human and animal studies indicate that Glassia may be able to treat and reduce the severity of GVHD occurring after allogeneic stem cell transplant.

Researchers are now evaluating Glassia in a phase 1/2 study of 24 GVHD patients with inadequate responses to steroid treatment following allogeneic stem cell transplant. The patients are enrolled in 4 dose cohorts, in which they receive up to 8 doses of Glassia. Interim data from this study is expected by the end of this year.

“Results from this phase 1/2 study in GVHD may support global clinical development activities and may serve as a platform to apply for an expansion of the AAT indications to include general organ transplantation, based on a similar mechanism of action,“ said David Tsur, Co-founder and Chief Executive Officer of Kamada, makers of Glassia.

“GVHD is a disease of significant unmet medical need, and both the disease and current therapy options carry considerable side effects. Given the favorable safety profile of Glassia, there is a strong rationale to support the development of this new indication and an increased likelihood of it becoming an effective therapy for this potentially life-threatening disease.”

“We will pursue discussion with the US and European regulators with regard to our development pathway and with an aim to move forward with a more advanced study of Glassia to treat GVHD.”

For more information on Glassia, see the full prescribing information.

Vials of drug

Credit: Bill Branson

The US Food and Drug Administration (FDA) has granted orphan designation for a human alpha-1 antitrypsin (AAT) product known as Glassia to treat graft-vs-host disease (GVHD).

Orphan drug designation carries multiple benefits, including the availability of grant money, certain tax credits, and 7 years of market exclusivity, as well as the possibility of an expedited regulatory process.

Glassia is the first available ready-to-infuse liquid alpha1-proteinase inhibitor.

The product is already approved by the FDA to treat adults with clinically evident emphysema due to severe congenital AAT deficiency. Glassia is given intravenously once a week to augment the levels of AAT, a protein derived from human plasma, in the blood.

In recent years, researchers have discovered that AAT has anti-inflammatory, tissue protective, immunomodulatory, and anti-apoptotic properties in direct or indirect consequence of its underlying antiprotease capabilities.

These properties may attenuate inflammation by lowering levels of proinflammatory mediators such as cytokines, chemokines, and proteases that are associated with GVHD.

Preliminary human and animal studies indicate that Glassia may be able to treat and reduce the severity of GVHD occurring after allogeneic stem cell transplant.

Researchers are now evaluating Glassia in a phase 1/2 study of 24 GVHD patients with inadequate responses to steroid treatment following allogeneic stem cell transplant. The patients are enrolled in 4 dose cohorts, in which they receive up to 8 doses of Glassia. Interim data from this study is expected by the end of this year.

“Results from this phase 1/2 study in GVHD may support global clinical development activities and may serve as a platform to apply for an expansion of the AAT indications to include general organ transplantation, based on a similar mechanism of action,“ said David Tsur, Co-founder and Chief Executive Officer of Kamada, makers of Glassia.

“GVHD is a disease of significant unmet medical need, and both the disease and current therapy options carry considerable side effects. Given the favorable safety profile of Glassia, there is a strong rationale to support the development of this new indication and an increased likelihood of it becoming an effective therapy for this potentially life-threatening disease.”

“We will pursue discussion with the US and European regulators with regard to our development pathway and with an aim to move forward with a more advanced study of Glassia to treat GVHD.”

For more information on Glassia, see the full prescribing information.

The Centers for Disease Control and Prevention has released “Essentials for Parenting Toddlers and Preschoolers,” an online guide for parents of children 2-4 years of age. The free online resource provides parents with information and recommendations for how to address various concerns that may arise in parenting young children.

The first section in the series, “Communicating with Your Child,” offers resources for parents to develop positive, open communication with toddlers and foster a stronger relationship with children. These skills will come in handy when the child is older and parents may wish to discuss difficult topics such as drugs and alcohol, the CDC said.

© BananaStock/Thinkstock

According to the agency, praise and active listening are two essential skills parents can use when communicating with young children. They offer the following tips:

1. When a child does something right, praise the child. Praise can include actions such as positive verbal reinforcement, hugs, or high fives. This increases the likelihood that he or she will repeat the desired behavior. Likewise, to lessen negative behavior, you may choose to use negative attention such as yelling, correcting, or ignoring the behavior.

2. When a child is talking to you, give him or her your full attention. This will reassure the child that you care about what he or she has to say.

3. Designate time every day to talk and play with your child. This lets children know they are important and helps create a stronger bond.

To read more about effective communication skills with toddlers and preschoolers, visit the CDC website. To view examples of good communication, watch the video, “How to Use Positive Communication.”

[email protected]

The Centers for Disease Control and Prevention has released “Essentials for Parenting Toddlers and Preschoolers,” an online guide for parents of children 2-4 years of age. The free online resource provides parents with information and recommendations for how to address various concerns that may arise in parenting young children.

The first section in the series, “Communicating with Your Child,” offers resources for parents to develop positive, open communication with toddlers and foster a stronger relationship with children. These skills will come in handy when the child is older and parents may wish to discuss difficult topics such as drugs and alcohol, the CDC said.

© BananaStock/Thinkstock

According to the agency, praise and active listening are two essential skills parents can use when communicating with young children. They offer the following tips:

1. When a child does something right, praise the child. Praise can include actions such as positive verbal reinforcement, hugs, or high fives. This increases the likelihood that he or she will repeat the desired behavior. Likewise, to lessen negative behavior, you may choose to use negative attention such as yelling, correcting, or ignoring the behavior.

2. When a child is talking to you, give him or her your full attention. This will reassure the child that you care about what he or she has to say.

3. Designate time every day to talk and play with your child. This lets children know they are important and helps create a stronger bond.

To read more about effective communication skills with toddlers and preschoolers, visit the CDC website. To view examples of good communication, watch the video, “How to Use Positive Communication.”

[email protected]

The Centers for Disease Control and Prevention has released “Essentials for Parenting Toddlers and Preschoolers,” an online guide for parents of children 2-4 years of age. The free online resource provides parents with information and recommendations for how to address various concerns that may arise in parenting young children.

The first section in the series, “Communicating with Your Child,” offers resources for parents to develop positive, open communication with toddlers and foster a stronger relationship with children. These skills will come in handy when the child is older and parents may wish to discuss difficult topics such as drugs and alcohol, the CDC said.

© BananaStock/Thinkstock

According to the agency, praise and active listening are two essential skills parents can use when communicating with young children. They offer the following tips:

1. When a child does something right, praise the child. Praise can include actions such as positive verbal reinforcement, hugs, or high fives. This increases the likelihood that he or she will repeat the desired behavior. Likewise, to lessen negative behavior, you may choose to use negative attention such as yelling, correcting, or ignoring the behavior.

2. When a child is talking to you, give him or her your full attention. This will reassure the child that you care about what he or she has to say.

3. Designate time every day to talk and play with your child. This lets children know they are important and helps create a stronger bond.

To read more about effective communication skills with toddlers and preschoolers, visit the CDC website. To view examples of good communication, watch the video, “How to Use Positive Communication.”

[email protected]