Restrictions on the number of buprenorphine prescriptions a physician can write in a given year do not hinder addiction treatment, as some had feared, according to a Research Letter published online Sept. 20 in JAMA.

Physicians who wish to treat opioid use disorders using buprenorphine are allowed to prescribe the drug to up to 30 patients during the first year they offer the treatment, and after that, they may request that the limit be increased to 100 patients. Some experts have expressed concern that this requirement may pose a barrier to buprenorphine therapy. To examine this possibility, researchers analyzed information in a database of prescriptions filled at retail pharmacies across the United States.

©Fuse/Thinkstock

The investigators focused on buprenorphine prescriptions filled during a 3-year period in seven states with the highest rates of addiction therapy: California, Florida, Massachusetts, Michigan, New York, Pennsylvania, and Texas. They identified 3,234 physician prescribers and 245,016 patients receiving a new buprenorphine prescription during the study period, said Bradley D. Stein, MD, PhD, of the RAND Corporation, Pittsburgh, and his associates.

A substantial proportion of the physician prescribers – 20% – treated only 1-3 patients, and an additional 49% treated fewer than the 30-patient limit. Only 9% of physician prescribers treated more than 75 patients. So the restrictions on the number of concurrent prescriptions do not appear to pose a barrier to buprenorphine therapy, Dr. Stein and his associates said (JAMA. 2016 Sep 20;316[11]:1211-2).

An unexpected finding was that the median duration of buprenorphine therapy was only 53 days, even though clinical recommendations specify that up to 12 months of treatment is beneficial, and longer duration of therapy is associated with better outcomes.

These findings indicate that strategies for improving access to addiction therapy may not need to target prescription limits, the investigators said.

Dr. Stein and his associates said their research was supported by the National Institute on Drug Abuse. He reported having served on the advisory board of Otsuka Pharmaceuticals, and the other investigators reported receiving royalties from Cambridge University Press and UpToDate.

Restrictions on the number of buprenorphine prescriptions a physician can write in a given year do not hinder addiction treatment, as some had feared, according to a Research Letter published online Sept. 20 in JAMA.

Physicians who wish to treat opioid use disorders using buprenorphine are allowed to prescribe the drug to up to 30 patients during the first year they offer the treatment, and after that, they may request that the limit be increased to 100 patients. Some experts have expressed concern that this requirement may pose a barrier to buprenorphine therapy. To examine this possibility, researchers analyzed information in a database of prescriptions filled at retail pharmacies across the United States.

©Fuse/Thinkstock

The investigators focused on buprenorphine prescriptions filled during a 3-year period in seven states with the highest rates of addiction therapy: California, Florida, Massachusetts, Michigan, New York, Pennsylvania, and Texas. They identified 3,234 physician prescribers and 245,016 patients receiving a new buprenorphine prescription during the study period, said Bradley D. Stein, MD, PhD, of the RAND Corporation, Pittsburgh, and his associates.

A substantial proportion of the physician prescribers – 20% – treated only 1-3 patients, and an additional 49% treated fewer than the 30-patient limit. Only 9% of physician prescribers treated more than 75 patients. So the restrictions on the number of concurrent prescriptions do not appear to pose a barrier to buprenorphine therapy, Dr. Stein and his associates said (JAMA. 2016 Sep 20;316[11]:1211-2).

An unexpected finding was that the median duration of buprenorphine therapy was only 53 days, even though clinical recommendations specify that up to 12 months of treatment is beneficial, and longer duration of therapy is associated with better outcomes.

These findings indicate that strategies for improving access to addiction therapy may not need to target prescription limits, the investigators said.

Dr. Stein and his associates said their research was supported by the National Institute on Drug Abuse. He reported having served on the advisory board of Otsuka Pharmaceuticals, and the other investigators reported receiving royalties from Cambridge University Press and UpToDate.

Restrictions on the number of buprenorphine prescriptions a physician can write in a given year do not hinder addiction treatment, as some had feared, according to a Research Letter published online Sept. 20 in JAMA.

Physicians who wish to treat opioid use disorders using buprenorphine are allowed to prescribe the drug to up to 30 patients during the first year they offer the treatment, and after that, they may request that the limit be increased to 100 patients. Some experts have expressed concern that this requirement may pose a barrier to buprenorphine therapy. To examine this possibility, researchers analyzed information in a database of prescriptions filled at retail pharmacies across the United States.

©Fuse/Thinkstock

The investigators focused on buprenorphine prescriptions filled during a 3-year period in seven states with the highest rates of addiction therapy: California, Florida, Massachusetts, Michigan, New York, Pennsylvania, and Texas. They identified 3,234 physician prescribers and 245,016 patients receiving a new buprenorphine prescription during the study period, said Bradley D. Stein, MD, PhD, of the RAND Corporation, Pittsburgh, and his associates.

A substantial proportion of the physician prescribers – 20% – treated only 1-3 patients, and an additional 49% treated fewer than the 30-patient limit. Only 9% of physician prescribers treated more than 75 patients. So the restrictions on the number of concurrent prescriptions do not appear to pose a barrier to buprenorphine therapy, Dr. Stein and his associates said (JAMA. 2016 Sep 20;316[11]:1211-2).

An unexpected finding was that the median duration of buprenorphine therapy was only 53 days, even though clinical recommendations specify that up to 12 months of treatment is beneficial, and longer duration of therapy is associated with better outcomes.

These findings indicate that strategies for improving access to addiction therapy may not need to target prescription limits, the investigators said.

Dr. Stein and his associates said their research was supported by the National Institute on Drug Abuse. He reported having served on the advisory board of Otsuka Pharmaceuticals, and the other investigators reported receiving royalties from Cambridge University Press and UpToDate.

LONDON – In chronic obstructive pulmonary disease (COPD), the advantage of a long-acting beta agonist (LABA) plus a long-acting muscarinic antagonist (LAMA) over a LABA plus an inhaled corticosteroid (ICS) was observed in every subgroup in the FLAME trial evaluated, according to post hoc analyses presented at the annual congress of the European Respiratory Society.

“We thought that we might not see the difference in the COPD patients with more severe disease, but the advantage was consistent even among those who entered the trial on triple therapy,” reported Jadwiga A. Wedzicha, MD, professor of respiratory medicine at the National Heart and Lung Institute, Imperial College, London.

FLAME, the recently published study that compared LABA/LAMA to LABA/ICS, was planned as a noninferiority study with the underlying hypothesis that LABA/LAMA would perform as well as LABA/ICS for the primary outcome of annual rate of COPD exacerbations (N Engl J Med. 2016;374:2222-34). Instead, the 11% lower rate of exacerbations for LABA/LAMA proved statistically significant (P = .003).

Six post hoc FLAME analyses were presented at the 2016 ERS Congress to further explore this result. All supported the main result. In addition to evaluating those who entered the trial on a LABA/LAMA/ICS triple-therapy combination, the analyses covered a broad array of subgroups defined by age, smoking history, and COPD severity as defined by Global Initiative for Chronic Obstructive Lung Disease (GOLD) classifications.

In FLAME, 3,362 COPD patients who had at least one exacerbation in the preceding year were randomized to the LABA indacaterol (110 mcg) plus the LAMA glycopyrronium (50 mcg) once daily or the combination of the LABA salmeterol (50 mcg) and the ICS fluticasone (500 mcg) twice daily. In addition to the relative advantage on the primary outcome of any exacerbation, the LABA/LAMA combination also significantly reduced the rate of moderate to severe exacerbations (P less than .001), and it extended the times to the first moderate to severe exacerbation (P less than .001) and the first severe exacerbation (P = .046), according to the published data.

In the post hoc analyses, the advantage of LABA/LAMA relative to LAMA/ICS was remarkably consistent. For example, in stratifications made for age (less than 55 years, 55 to less than 65 years, 65-75 years, and greater than or equal to 75 years) at least a numerical advantage of LABA/LAMA was seen in all age groups for prevention of any exacerbation, and the difference reached statistical significance for those in the age group 55 to greater than 65 years. For prevention of moderate to severe exacerbations, the treatments were found to be equivalent for individuals younger than 55 years, but LABA/LAMA was statistically superior for the other three age categories.

For ex-smokers, unlike current smokers, the numerical advantage of LABA/LAMA over LABA/ICS for reduction in the rate ratio of all exacerbations did not reach statistical significance, but the LABA/LAMA combination did provide a statistically significant advantage for both ex-smokers and current smokers for moderate to severe exacerbations.

For patients with two or more exacerbations in the year prior to enrollment in FLAME, the relative degree of protection was of magnitude similar to that of patients with only one exacerbation even though the relative advantage in those with multiple prior exacerbations did not reach statistical significance. However, the lack of significance was likely due to the relatively small number of patients in this subpopulation, according to Dr. Wedzicha.

Similarly, the LABA/LAMA combination was at least numerically superior to LABA/ICS for all exacerbations and for moderate to severe exacerbations across GOLD classifications with one exception. When compared for relative protection against moderate to severe exacerbations, there was a slight and nonsignificant disadvantage for LABA/LAMA, but, again, Dr. Wedzicha reported, “the number of patients in this subgroup was quite small.”

In another FLAME post hoc analysis, the odds ratio (OR) for exacerbations among the 1,893 patients (56.3%) who were on ICS at study entry was found to be almost identical to the OR among those who were not. Specifically, the ORs for all exacerbations and moderate to severe exacerbations were 0.88 (P = .008) and 0.86 (P = .018), respectively, for those previously treated with ICS and 0.88 (P = .021) and 0.78 (P = .002), respectively, for those who had not been treated with ICS.

The LABA/LAMA combination was also superior to LABA/ICS for improvements in quality of life, which was measured via the St. George’s Respiratory Questionnaire. With an improvement of at least four units on the St. George’s Respiratory Questionnaire defined as clinically meaningful, 49.5% of LABA/LAMA patients versus 43.8% of LABA/ICS patients (P less than .024) benefited on this measure.

Overall, the results from the FLAME post hoc analyses have demonstrated “remarkable consistency,” Dr. Wedzicha reported. Taken together, she said the data “imply that LABA/LAMA is the first choice of treatment for COPD patients at risk of exacerbation.”

LONDON – In chronic obstructive pulmonary disease (COPD), the advantage of a long-acting beta agonist (LABA) plus a long-acting muscarinic antagonist (LAMA) over a LABA plus an inhaled corticosteroid (ICS) was observed in every subgroup in the FLAME trial evaluated, according to post hoc analyses presented at the annual congress of the European Respiratory Society.

“We thought that we might not see the difference in the COPD patients with more severe disease, but the advantage was consistent even among those who entered the trial on triple therapy,” reported Jadwiga A. Wedzicha, MD, professor of respiratory medicine at the National Heart and Lung Institute, Imperial College, London.

FLAME, the recently published study that compared LABA/LAMA to LABA/ICS, was planned as a noninferiority study with the underlying hypothesis that LABA/LAMA would perform as well as LABA/ICS for the primary outcome of annual rate of COPD exacerbations (N Engl J Med. 2016;374:2222-34). Instead, the 11% lower rate of exacerbations for LABA/LAMA proved statistically significant (P = .003).

Six post hoc FLAME analyses were presented at the 2016 ERS Congress to further explore this result. All supported the main result. In addition to evaluating those who entered the trial on a LABA/LAMA/ICS triple-therapy combination, the analyses covered a broad array of subgroups defined by age, smoking history, and COPD severity as defined by Global Initiative for Chronic Obstructive Lung Disease (GOLD) classifications.

In FLAME, 3,362 COPD patients who had at least one exacerbation in the preceding year were randomized to the LABA indacaterol (110 mcg) plus the LAMA glycopyrronium (50 mcg) once daily or the combination of the LABA salmeterol (50 mcg) and the ICS fluticasone (500 mcg) twice daily. In addition to the relative advantage on the primary outcome of any exacerbation, the LABA/LAMA combination also significantly reduced the rate of moderate to severe exacerbations (P less than .001), and it extended the times to the first moderate to severe exacerbation (P less than .001) and the first severe exacerbation (P = .046), according to the published data.

In the post hoc analyses, the advantage of LABA/LAMA relative to LAMA/ICS was remarkably consistent. For example, in stratifications made for age (less than 55 years, 55 to less than 65 years, 65-75 years, and greater than or equal to 75 years) at least a numerical advantage of LABA/LAMA was seen in all age groups for prevention of any exacerbation, and the difference reached statistical significance for those in the age group 55 to greater than 65 years. For prevention of moderate to severe exacerbations, the treatments were found to be equivalent for individuals younger than 55 years, but LABA/LAMA was statistically superior for the other three age categories.

For ex-smokers, unlike current smokers, the numerical advantage of LABA/LAMA over LABA/ICS for reduction in the rate ratio of all exacerbations did not reach statistical significance, but the LABA/LAMA combination did provide a statistically significant advantage for both ex-smokers and current smokers for moderate to severe exacerbations.

For patients with two or more exacerbations in the year prior to enrollment in FLAME, the relative degree of protection was of magnitude similar to that of patients with only one exacerbation even though the relative advantage in those with multiple prior exacerbations did not reach statistical significance. However, the lack of significance was likely due to the relatively small number of patients in this subpopulation, according to Dr. Wedzicha.

Similarly, the LABA/LAMA combination was at least numerically superior to LABA/ICS for all exacerbations and for moderate to severe exacerbations across GOLD classifications with one exception. When compared for relative protection against moderate to severe exacerbations, there was a slight and nonsignificant disadvantage for LABA/LAMA, but, again, Dr. Wedzicha reported, “the number of patients in this subgroup was quite small.”

In another FLAME post hoc analysis, the odds ratio (OR) for exacerbations among the 1,893 patients (56.3%) who were on ICS at study entry was found to be almost identical to the OR among those who were not. Specifically, the ORs for all exacerbations and moderate to severe exacerbations were 0.88 (P = .008) and 0.86 (P = .018), respectively, for those previously treated with ICS and 0.88 (P = .021) and 0.78 (P = .002), respectively, for those who had not been treated with ICS.

The LABA/LAMA combination was also superior to LABA/ICS for improvements in quality of life, which was measured via the St. George’s Respiratory Questionnaire. With an improvement of at least four units on the St. George’s Respiratory Questionnaire defined as clinically meaningful, 49.5% of LABA/LAMA patients versus 43.8% of LABA/ICS patients (P less than .024) benefited on this measure.

Overall, the results from the FLAME post hoc analyses have demonstrated “remarkable consistency,” Dr. Wedzicha reported. Taken together, she said the data “imply that LABA/LAMA is the first choice of treatment for COPD patients at risk of exacerbation.”

LONDON – In chronic obstructive pulmonary disease (COPD), the advantage of a long-acting beta agonist (LABA) plus a long-acting muscarinic antagonist (LAMA) over a LABA plus an inhaled corticosteroid (ICS) was observed in every subgroup in the FLAME trial evaluated, according to post hoc analyses presented at the annual congress of the European Respiratory Society.

“We thought that we might not see the difference in the COPD patients with more severe disease, but the advantage was consistent even among those who entered the trial on triple therapy,” reported Jadwiga A. Wedzicha, MD, professor of respiratory medicine at the National Heart and Lung Institute, Imperial College, London.

FLAME, the recently published study that compared LABA/LAMA to LABA/ICS, was planned as a noninferiority study with the underlying hypothesis that LABA/LAMA would perform as well as LABA/ICS for the primary outcome of annual rate of COPD exacerbations (N Engl J Med. 2016;374:2222-34). Instead, the 11% lower rate of exacerbations for LABA/LAMA proved statistically significant (P = .003).

Six post hoc FLAME analyses were presented at the 2016 ERS Congress to further explore this result. All supported the main result. In addition to evaluating those who entered the trial on a LABA/LAMA/ICS triple-therapy combination, the analyses covered a broad array of subgroups defined by age, smoking history, and COPD severity as defined by Global Initiative for Chronic Obstructive Lung Disease (GOLD) classifications.

In FLAME, 3,362 COPD patients who had at least one exacerbation in the preceding year were randomized to the LABA indacaterol (110 mcg) plus the LAMA glycopyrronium (50 mcg) once daily or the combination of the LABA salmeterol (50 mcg) and the ICS fluticasone (500 mcg) twice daily. In addition to the relative advantage on the primary outcome of any exacerbation, the LABA/LAMA combination also significantly reduced the rate of moderate to severe exacerbations (P less than .001), and it extended the times to the first moderate to severe exacerbation (P less than .001) and the first severe exacerbation (P = .046), according to the published data.

In the post hoc analyses, the advantage of LABA/LAMA relative to LAMA/ICS was remarkably consistent. For example, in stratifications made for age (less than 55 years, 55 to less than 65 years, 65-75 years, and greater than or equal to 75 years) at least a numerical advantage of LABA/LAMA was seen in all age groups for prevention of any exacerbation, and the difference reached statistical significance for those in the age group 55 to greater than 65 years. For prevention of moderate to severe exacerbations, the treatments were found to be equivalent for individuals younger than 55 years, but LABA/LAMA was statistically superior for the other three age categories.

For ex-smokers, unlike current smokers, the numerical advantage of LABA/LAMA over LABA/ICS for reduction in the rate ratio of all exacerbations did not reach statistical significance, but the LABA/LAMA combination did provide a statistically significant advantage for both ex-smokers and current smokers for moderate to severe exacerbations.

For patients with two or more exacerbations in the year prior to enrollment in FLAME, the relative degree of protection was of magnitude similar to that of patients with only one exacerbation even though the relative advantage in those with multiple prior exacerbations did not reach statistical significance. However, the lack of significance was likely due to the relatively small number of patients in this subpopulation, according to Dr. Wedzicha.

Similarly, the LABA/LAMA combination was at least numerically superior to LABA/ICS for all exacerbations and for moderate to severe exacerbations across GOLD classifications with one exception. When compared for relative protection against moderate to severe exacerbations, there was a slight and nonsignificant disadvantage for LABA/LAMA, but, again, Dr. Wedzicha reported, “the number of patients in this subgroup was quite small.”

In another FLAME post hoc analysis, the odds ratio (OR) for exacerbations among the 1,893 patients (56.3%) who were on ICS at study entry was found to be almost identical to the OR among those who were not. Specifically, the ORs for all exacerbations and moderate to severe exacerbations were 0.88 (P = .008) and 0.86 (P = .018), respectively, for those previously treated with ICS and 0.88 (P = .021) and 0.78 (P = .002), respectively, for those who had not been treated with ICS.

The LABA/LAMA combination was also superior to LABA/ICS for improvements in quality of life, which was measured via the St. George’s Respiratory Questionnaire. With an improvement of at least four units on the St. George’s Respiratory Questionnaire defined as clinically meaningful, 49.5% of LABA/LAMA patients versus 43.8% of LABA/ICS patients (P less than .024) benefited on this measure.

Overall, the results from the FLAME post hoc analyses have demonstrated “remarkable consistency,” Dr. Wedzicha reported. Taken together, she said the data “imply that LABA/LAMA is the first choice of treatment for COPD patients at risk of exacerbation.”

VIENNA – Recombinant human erythropoietin appears to be a cognitive enhancer in patients with unipolar or bipolar depression accompanied by cognitive impairment, Kamilla W. Miskowiak, PhD, reported at the annual congress of the European College of Neuropsychopharmacology.

She presented a pooled analysis of her two pilot randomized, placebo-controlled clinical trials totaling 79 patients with treatment-resistant unipolar or partly remitted bipolar depression associated with baseline cognitive impairment. She found that 8 weeks of once-weekly intravenous infusions of high-dose human recombinant erythropoetin (Epogen), also known as epoetin alfa (EPO), resulted in clinically meaningful improvement in cognition 1 week post treatment, as measured on neuropsychological tests assessing the speed of complex cognitive processing, verbal memory, attention span, concentration, working memory, and strategic planning ability. Saline infusions had no effect.

Moreover, follow-up testing conducted 6 weeks after the final treatment session showed continued full maintenance of the initial cognitive gains, which averaged an 11% improvement over baseline. The full duration of effect will be determined in the next round of studies, which will feature 12 weeks of EPO and 6 months of off-treatment follow-up, added Dr. Miskowiak, a senior research psychologist at the University of Copenhagen.

In an interview, she emphasized that the mechanism of benefit doesn’t appear to be related to EPO’s signature ability to boost red blood cell (RBC) production and raise hemoglobin levels. After all, she noted, RBCs were back to normal within 2 weeks after treatment ended, yet the objective cognitive improvements continued. Instead, the mechanism involves EPO’s capacity to enhance brain neuroplasticity, an effect that was demonstrated first in animal studies and subsequently in Dr. Miskowiak’s clinical trials.

“We did MRI functional and structural brain scans at baseline and after completion of treatment, and we saw that EPO increased left hippocampal volume. In fact, it was the structural change in hippocampal volume in response to EPO that was the single strongest predictor of cognitive improvement in multivariate analyses adjusted for age, illness chronicity, depressive symptom severity, gender, and other factors,” according to Dr. Miskowiak.

Physicians who use EPO to treat anemia might blanch at the doses of EPO administered to improve cognitive impairments in patients with affective disorders. Instead of giving 50-100 U/kg of body weight several times per week, as is common in treating anemia, the patients in her studies typically received 40,000 U/wk.

“We used much, much higher doses than are given to affect the bone marrow in patients with anemia, because only about 1% of the IV dose passes across the blood/brain barrier,” she explained.

Because EPO, even in conventional doses, is associated with an increased risk of blood clots, patients were ineligible for the cognition-improvement trials if they had a history of venous thromboembolism, coronary disease, or cancer. Moreover, their RBC and platelet activity levels were monitored on a weekly basis. No untoward effects were seen, Dr. Miskowiak continued.

“Patients really liked coming in for this therapy. Many of them were quite chronic, with years of illness, yet adherence was excellent,” she said.

Early in the developmental pipeline are an intranasal variant of EPO and a carbamylated EPO designed to cross the blood/brain barrier efficiently in order to achieve direct brain neuroplasticity-stimulating effects with minimal impact on RBC production.

Dr. Miskowiak stressed that EPO as a treatment for cognitive dysfunction associated with affective disorders is not ready for prime time use in clinical practice. The next round of randomized, placebo-controlled clinical trials, due to start early in 2017, will attempt to replicate her pilot study findings while pinning down the optimal dosing regimen. The new trials will feature longer off-treatment follow-up as well as quality-of-life measures and an economic analysis that includes assessment of the ability to return to work.

“This therapy may be attractive from an economic perspective,” according to the psychologist. “I don’t see this as first-line therapy in clinical practice, though,” she added. “It will be reserved for the more severely cognitively impaired patients.”

Eduard Vieta, MD, professor and chair of the department of psychiatry and psychology at the University of Barcelona, commented that cognitive impairment is now recognized as a core aspect of affective disorders. There is a huge unmet need for treatments that address this disease aspect. The drugs now available for treatment of bipolar disorder and unipolar depression don’t improve the associated cognitive impairments. Indeed, up to 40% of patients in remission from major depressive disorder and 70% in remission from bipolar disorder continue to experience neurocognitive symptoms.

Dr. Miskowiak’s work was funded by the Danish Ministry of Science, Innovation, and Higher Education. She reported having no relevant financial conflicts of interest.

[email protected]

VIENNA – Recombinant human erythropoietin appears to be a cognitive enhancer in patients with unipolar or bipolar depression accompanied by cognitive impairment, Kamilla W. Miskowiak, PhD, reported at the annual congress of the European College of Neuropsychopharmacology.

She presented a pooled analysis of her two pilot randomized, placebo-controlled clinical trials totaling 79 patients with treatment-resistant unipolar or partly remitted bipolar depression associated with baseline cognitive impairment. She found that 8 weeks of once-weekly intravenous infusions of high-dose human recombinant erythropoetin (Epogen), also known as epoetin alfa (EPO), resulted in clinically meaningful improvement in cognition 1 week post treatment, as measured on neuropsychological tests assessing the speed of complex cognitive processing, verbal memory, attention span, concentration, working memory, and strategic planning ability. Saline infusions had no effect.

Moreover, follow-up testing conducted 6 weeks after the final treatment session showed continued full maintenance of the initial cognitive gains, which averaged an 11% improvement over baseline. The full duration of effect will be determined in the next round of studies, which will feature 12 weeks of EPO and 6 months of off-treatment follow-up, added Dr. Miskowiak, a senior research psychologist at the University of Copenhagen.

In an interview, she emphasized that the mechanism of benefit doesn’t appear to be related to EPO’s signature ability to boost red blood cell (RBC) production and raise hemoglobin levels. After all, she noted, RBCs were back to normal within 2 weeks after treatment ended, yet the objective cognitive improvements continued. Instead, the mechanism involves EPO’s capacity to enhance brain neuroplasticity, an effect that was demonstrated first in animal studies and subsequently in Dr. Miskowiak’s clinical trials.

“We did MRI functional and structural brain scans at baseline and after completion of treatment, and we saw that EPO increased left hippocampal volume. In fact, it was the structural change in hippocampal volume in response to EPO that was the single strongest predictor of cognitive improvement in multivariate analyses adjusted for age, illness chronicity, depressive symptom severity, gender, and other factors,” according to Dr. Miskowiak.

Physicians who use EPO to treat anemia might blanch at the doses of EPO administered to improve cognitive impairments in patients with affective disorders. Instead of giving 50-100 U/kg of body weight several times per week, as is common in treating anemia, the patients in her studies typically received 40,000 U/wk.

“We used much, much higher doses than are given to affect the bone marrow in patients with anemia, because only about 1% of the IV dose passes across the blood/brain barrier,” she explained.

Because EPO, even in conventional doses, is associated with an increased risk of blood clots, patients were ineligible for the cognition-improvement trials if they had a history of venous thromboembolism, coronary disease, or cancer. Moreover, their RBC and platelet activity levels were monitored on a weekly basis. No untoward effects were seen, Dr. Miskowiak continued.

“Patients really liked coming in for this therapy. Many of them were quite chronic, with years of illness, yet adherence was excellent,” she said.

Early in the developmental pipeline are an intranasal variant of EPO and a carbamylated EPO designed to cross the blood/brain barrier efficiently in order to achieve direct brain neuroplasticity-stimulating effects with minimal impact on RBC production.

Dr. Miskowiak stressed that EPO as a treatment for cognitive dysfunction associated with affective disorders is not ready for prime time use in clinical practice. The next round of randomized, placebo-controlled clinical trials, due to start early in 2017, will attempt to replicate her pilot study findings while pinning down the optimal dosing regimen. The new trials will feature longer off-treatment follow-up as well as quality-of-life measures and an economic analysis that includes assessment of the ability to return to work.

“This therapy may be attractive from an economic perspective,” according to the psychologist. “I don’t see this as first-line therapy in clinical practice, though,” she added. “It will be reserved for the more severely cognitively impaired patients.”

Eduard Vieta, MD, professor and chair of the department of psychiatry and psychology at the University of Barcelona, commented that cognitive impairment is now recognized as a core aspect of affective disorders. There is a huge unmet need for treatments that address this disease aspect. The drugs now available for treatment of bipolar disorder and unipolar depression don’t improve the associated cognitive impairments. Indeed, up to 40% of patients in remission from major depressive disorder and 70% in remission from bipolar disorder continue to experience neurocognitive symptoms.

Dr. Miskowiak’s work was funded by the Danish Ministry of Science, Innovation, and Higher Education. She reported having no relevant financial conflicts of interest.

[email protected]

VIENNA – Recombinant human erythropoietin appears to be a cognitive enhancer in patients with unipolar or bipolar depression accompanied by cognitive impairment, Kamilla W. Miskowiak, PhD, reported at the annual congress of the European College of Neuropsychopharmacology.

She presented a pooled analysis of her two pilot randomized, placebo-controlled clinical trials totaling 79 patients with treatment-resistant unipolar or partly remitted bipolar depression associated with baseline cognitive impairment. She found that 8 weeks of once-weekly intravenous infusions of high-dose human recombinant erythropoetin (Epogen), also known as epoetin alfa (EPO), resulted in clinically meaningful improvement in cognition 1 week post treatment, as measured on neuropsychological tests assessing the speed of complex cognitive processing, verbal memory, attention span, concentration, working memory, and strategic planning ability. Saline infusions had no effect.

Moreover, follow-up testing conducted 6 weeks after the final treatment session showed continued full maintenance of the initial cognitive gains, which averaged an 11% improvement over baseline. The full duration of effect will be determined in the next round of studies, which will feature 12 weeks of EPO and 6 months of off-treatment follow-up, added Dr. Miskowiak, a senior research psychologist at the University of Copenhagen.

In an interview, she emphasized that the mechanism of benefit doesn’t appear to be related to EPO’s signature ability to boost red blood cell (RBC) production and raise hemoglobin levels. After all, she noted, RBCs were back to normal within 2 weeks after treatment ended, yet the objective cognitive improvements continued. Instead, the mechanism involves EPO’s capacity to enhance brain neuroplasticity, an effect that was demonstrated first in animal studies and subsequently in Dr. Miskowiak’s clinical trials.

“We did MRI functional and structural brain scans at baseline and after completion of treatment, and we saw that EPO increased left hippocampal volume. In fact, it was the structural change in hippocampal volume in response to EPO that was the single strongest predictor of cognitive improvement in multivariate analyses adjusted for age, illness chronicity, depressive symptom severity, gender, and other factors,” according to Dr. Miskowiak.

Physicians who use EPO to treat anemia might blanch at the doses of EPO administered to improve cognitive impairments in patients with affective disorders. Instead of giving 50-100 U/kg of body weight several times per week, as is common in treating anemia, the patients in her studies typically received 40,000 U/wk.

“We used much, much higher doses than are given to affect the bone marrow in patients with anemia, because only about 1% of the IV dose passes across the blood/brain barrier,” she explained.

Because EPO, even in conventional doses, is associated with an increased risk of blood clots, patients were ineligible for the cognition-improvement trials if they had a history of venous thromboembolism, coronary disease, or cancer. Moreover, their RBC and platelet activity levels were monitored on a weekly basis. No untoward effects were seen, Dr. Miskowiak continued.

“Patients really liked coming in for this therapy. Many of them were quite chronic, with years of illness, yet adherence was excellent,” she said.

Early in the developmental pipeline are an intranasal variant of EPO and a carbamylated EPO designed to cross the blood/brain barrier efficiently in order to achieve direct brain neuroplasticity-stimulating effects with minimal impact on RBC production.

Dr. Miskowiak stressed that EPO as a treatment for cognitive dysfunction associated with affective disorders is not ready for prime time use in clinical practice. The next round of randomized, placebo-controlled clinical trials, due to start early in 2017, will attempt to replicate her pilot study findings while pinning down the optimal dosing regimen. The new trials will feature longer off-treatment follow-up as well as quality-of-life measures and an economic analysis that includes assessment of the ability to return to work.

“This therapy may be attractive from an economic perspective,” according to the psychologist. “I don’t see this as first-line therapy in clinical practice, though,” she added. “It will be reserved for the more severely cognitively impaired patients.”

Eduard Vieta, MD, professor and chair of the department of psychiatry and psychology at the University of Barcelona, commented that cognitive impairment is now recognized as a core aspect of affective disorders. There is a huge unmet need for treatments that address this disease aspect. The drugs now available for treatment of bipolar disorder and unipolar depression don’t improve the associated cognitive impairments. Indeed, up to 40% of patients in remission from major depressive disorder and 70% in remission from bipolar disorder continue to experience neurocognitive symptoms.

Dr. Miskowiak’s work was funded by the Danish Ministry of Science, Innovation, and Higher Education. She reported having no relevant financial conflicts of interest.

[email protected]

LONDON – Siponimod delayed disability progression in patients with secondary progressive multiple sclerosis, according to top-line findings from the phase III EXPAND study.

Siponimod reduced the primary endpoint of the time to 3-month confirmed disease progression (CDP) assessed via the Expanded Disability Status Scale (EDSS) by 21%, compared with placebo (P = .013).

“It is reassuring that this primary outcome is supported by an important secondary outcome of the time to CDP at 6 months,” presenting author Ludwig Kappos, MD, of University Hospital Basel (Switzerland), said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

He reported that a 26% reduction in the 6-month CDP was also observed comparing the active and placebo treatments (P = .006) in the multicenter, randomized, double-blind trial that involved 1,646 patients “with the whole spectrum” of secondary progressive multiple sclerosis (SPMS).

The findings build on those of the phase II BOLD study in patients with relapsing-remitting MS (RRMS) (Lancet Neurol. 2013;12[8]:756-67) and showed a reduction in relapse rates and a reduction in the number of brain lesions seen on MRI scans for siponimod, compared with placebo.

Recently reported data from the 24-month extension of the BOLD phase II trial (JAMA Neurol. 2016;73[9]:1089-98) also showed that disease activity was low in patients treated with siponimod, and that there were no new safety signals. Dose reduction during initiation mitigated cardiac adverse effects, an approach that was also used successfully in the phase III study.

Siponimod is a once-daily oral treatment being developed by Novartis for the treatment of MS. Like fingolimod (Gilenya), which is licensed for the treatment of RRMS, siponimod is a selective sphingosine 1-phosphate receptor (S1P) modulator. Unlike fingolimod, which targets S1P subtypes 1, 3, 4, and 5, siponimod only targets the S1P 1 and 5 subtypes.

Fingolimod is also known to cause temporary changes in heart rate, heartbeat, and blood pressure, which necessitates early electrocardiographic monitoring during the first 6 hours when the drug is first given. At the present time, it doesn’t seem that siponimod will have unwanted cardiac effects, but longer-term follow-up data are needed.

“Adverse events were as you would expect with an S1P receptor modulator,” Dr. Kappos said, noting that there was nothing new. Overall, any adverse event occurred in 88% of actively-treated and 81% of placebo-treated patients. The rate of serious adverse events was similar in the siponimod (3.8%) and placebo (3.7%) arms, and a similar percentage of patients were reported to have infections (48% and 49%, respectively).

Analysis of all the various secondary endpoints is still ongoing; Dr. Kappos noted that the primary endpoint data had just recently become available. Some initial findings, however, show benefit for siponimod over placebo.

The change in T2 lesion volume from baseline to both 12 and 24 months was significantly less with siponimod than with placebo, at a 79.1% lower average change (P less than .0001).

The annualized relapse rate was reduced by 55% with the active treatment versus placebo, and there was less percent change in brain volume with active therapy versus placebo from baseline to 12 and 24 months’ follow-up (23.4% lower average change, P = .0002).

The time to 3-month confirmed worsening by 20% or more from baseline in the timed 25-foot walk test was reduced by 6.2%. Although not significant, the trend was “in the right direction,” Dr. Kappos said.

The mean age of recruited patients was 48 years, with an average duration of MS of 16-17 years, and just under 4 years since their conversion to SPMS. Baseline EDSS was a mean of 5.4, around 35%-37% had one or more relapses in the 2 years before screening, and 20% had gadolinium-enhancing lesions at baseline.

A variety of predefined subgroup analyses showed a benefit for siponimod over placebo. These included analyses looking at the effect by the number of gadolinium-enhancing lesions at baseline, previous disease-modifying treatment, whether patients’ MS was rapidly progressing, whether patients’ disease was moderate or severe, the baseline EDSS, and the duration of MS since the first recognition of symptoms.

“What is the optimal patient population?” an audience member asked Dr. Kappos during the Q&A period following his presentation at the ECTRIMS meeting. He responded: “I think younger patients with the more active disease will certainly be the best candidates.” But, he added, it was reassuring to note that the drug seems to work equally well in all patient subtypes.

Novartis funded the study. Dr. Kappos disclosed that his institution has received financial support for research purposes from multiple MS drug manufacturers – including Novartis – and charitable organizations.

LONDON – Siponimod delayed disability progression in patients with secondary progressive multiple sclerosis, according to top-line findings from the phase III EXPAND study.

Siponimod reduced the primary endpoint of the time to 3-month confirmed disease progression (CDP) assessed via the Expanded Disability Status Scale (EDSS) by 21%, compared with placebo (P = .013).

“It is reassuring that this primary outcome is supported by an important secondary outcome of the time to CDP at 6 months,” presenting author Ludwig Kappos, MD, of University Hospital Basel (Switzerland), said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

He reported that a 26% reduction in the 6-month CDP was also observed comparing the active and placebo treatments (P = .006) in the multicenter, randomized, double-blind trial that involved 1,646 patients “with the whole spectrum” of secondary progressive multiple sclerosis (SPMS).

The findings build on those of the phase II BOLD study in patients with relapsing-remitting MS (RRMS) (Lancet Neurol. 2013;12[8]:756-67) and showed a reduction in relapse rates and a reduction in the number of brain lesions seen on MRI scans for siponimod, compared with placebo.

Recently reported data from the 24-month extension of the BOLD phase II trial (JAMA Neurol. 2016;73[9]:1089-98) also showed that disease activity was low in patients treated with siponimod, and that there were no new safety signals. Dose reduction during initiation mitigated cardiac adverse effects, an approach that was also used successfully in the phase III study.

Siponimod is a once-daily oral treatment being developed by Novartis for the treatment of MS. Like fingolimod (Gilenya), which is licensed for the treatment of RRMS, siponimod is a selective sphingosine 1-phosphate receptor (S1P) modulator. Unlike fingolimod, which targets S1P subtypes 1, 3, 4, and 5, siponimod only targets the S1P 1 and 5 subtypes.

Fingolimod is also known to cause temporary changes in heart rate, heartbeat, and blood pressure, which necessitates early electrocardiographic monitoring during the first 6 hours when the drug is first given. At the present time, it doesn’t seem that siponimod will have unwanted cardiac effects, but longer-term follow-up data are needed.

“Adverse events were as you would expect with an S1P receptor modulator,” Dr. Kappos said, noting that there was nothing new. Overall, any adverse event occurred in 88% of actively-treated and 81% of placebo-treated patients. The rate of serious adverse events was similar in the siponimod (3.8%) and placebo (3.7%) arms, and a similar percentage of patients were reported to have infections (48% and 49%, respectively).

Analysis of all the various secondary endpoints is still ongoing; Dr. Kappos noted that the primary endpoint data had just recently become available. Some initial findings, however, show benefit for siponimod over placebo.

The change in T2 lesion volume from baseline to both 12 and 24 months was significantly less with siponimod than with placebo, at a 79.1% lower average change (P less than .0001).

The annualized relapse rate was reduced by 55% with the active treatment versus placebo, and there was less percent change in brain volume with active therapy versus placebo from baseline to 12 and 24 months’ follow-up (23.4% lower average change, P = .0002).

The time to 3-month confirmed worsening by 20% or more from baseline in the timed 25-foot walk test was reduced by 6.2%. Although not significant, the trend was “in the right direction,” Dr. Kappos said.

The mean age of recruited patients was 48 years, with an average duration of MS of 16-17 years, and just under 4 years since their conversion to SPMS. Baseline EDSS was a mean of 5.4, around 35%-37% had one or more relapses in the 2 years before screening, and 20% had gadolinium-enhancing lesions at baseline.

A variety of predefined subgroup analyses showed a benefit for siponimod over placebo. These included analyses looking at the effect by the number of gadolinium-enhancing lesions at baseline, previous disease-modifying treatment, whether patients’ MS was rapidly progressing, whether patients’ disease was moderate or severe, the baseline EDSS, and the duration of MS since the first recognition of symptoms.

“What is the optimal patient population?” an audience member asked Dr. Kappos during the Q&A period following his presentation at the ECTRIMS meeting. He responded: “I think younger patients with the more active disease will certainly be the best candidates.” But, he added, it was reassuring to note that the drug seems to work equally well in all patient subtypes.

Novartis funded the study. Dr. Kappos disclosed that his institution has received financial support for research purposes from multiple MS drug manufacturers – including Novartis – and charitable organizations.

LONDON – Siponimod delayed disability progression in patients with secondary progressive multiple sclerosis, according to top-line findings from the phase III EXPAND study.

Siponimod reduced the primary endpoint of the time to 3-month confirmed disease progression (CDP) assessed via the Expanded Disability Status Scale (EDSS) by 21%, compared with placebo (P = .013).

“It is reassuring that this primary outcome is supported by an important secondary outcome of the time to CDP at 6 months,” presenting author Ludwig Kappos, MD, of University Hospital Basel (Switzerland), said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

He reported that a 26% reduction in the 6-month CDP was also observed comparing the active and placebo treatments (P = .006) in the multicenter, randomized, double-blind trial that involved 1,646 patients “with the whole spectrum” of secondary progressive multiple sclerosis (SPMS).

The findings build on those of the phase II BOLD study in patients with relapsing-remitting MS (RRMS) (Lancet Neurol. 2013;12[8]:756-67) and showed a reduction in relapse rates and a reduction in the number of brain lesions seen on MRI scans for siponimod, compared with placebo.

Recently reported data from the 24-month extension of the BOLD phase II trial (JAMA Neurol. 2016;73[9]:1089-98) also showed that disease activity was low in patients treated with siponimod, and that there were no new safety signals. Dose reduction during initiation mitigated cardiac adverse effects, an approach that was also used successfully in the phase III study.

Siponimod is a once-daily oral treatment being developed by Novartis for the treatment of MS. Like fingolimod (Gilenya), which is licensed for the treatment of RRMS, siponimod is a selective sphingosine 1-phosphate receptor (S1P) modulator. Unlike fingolimod, which targets S1P subtypes 1, 3, 4, and 5, siponimod only targets the S1P 1 and 5 subtypes.

Fingolimod is also known to cause temporary changes in heart rate, heartbeat, and blood pressure, which necessitates early electrocardiographic monitoring during the first 6 hours when the drug is first given. At the present time, it doesn’t seem that siponimod will have unwanted cardiac effects, but longer-term follow-up data are needed.

“Adverse events were as you would expect with an S1P receptor modulator,” Dr. Kappos said, noting that there was nothing new. Overall, any adverse event occurred in 88% of actively-treated and 81% of placebo-treated patients. The rate of serious adverse events was similar in the siponimod (3.8%) and placebo (3.7%) arms, and a similar percentage of patients were reported to have infections (48% and 49%, respectively).

Analysis of all the various secondary endpoints is still ongoing; Dr. Kappos noted that the primary endpoint data had just recently become available. Some initial findings, however, show benefit for siponimod over placebo.

The change in T2 lesion volume from baseline to both 12 and 24 months was significantly less with siponimod than with placebo, at a 79.1% lower average change (P less than .0001).

The annualized relapse rate was reduced by 55% with the active treatment versus placebo, and there was less percent change in brain volume with active therapy versus placebo from baseline to 12 and 24 months’ follow-up (23.4% lower average change, P = .0002).

The time to 3-month confirmed worsening by 20% or more from baseline in the timed 25-foot walk test was reduced by 6.2%. Although not significant, the trend was “in the right direction,” Dr. Kappos said.

The mean age of recruited patients was 48 years, with an average duration of MS of 16-17 years, and just under 4 years since their conversion to SPMS. Baseline EDSS was a mean of 5.4, around 35%-37% had one or more relapses in the 2 years before screening, and 20% had gadolinium-enhancing lesions at baseline.

A variety of predefined subgroup analyses showed a benefit for siponimod over placebo. These included analyses looking at the effect by the number of gadolinium-enhancing lesions at baseline, previous disease-modifying treatment, whether patients’ MS was rapidly progressing, whether patients’ disease was moderate or severe, the baseline EDSS, and the duration of MS since the first recognition of symptoms.

“What is the optimal patient population?” an audience member asked Dr. Kappos during the Q&A period following his presentation at the ECTRIMS meeting. He responded: “I think younger patients with the more active disease will certainly be the best candidates.” But, he added, it was reassuring to note that the drug seems to work equally well in all patient subtypes.

Novartis funded the study. Dr. Kappos disclosed that his institution has received financial support for research purposes from multiple MS drug manufacturers – including Novartis – and charitable organizations.

We are pleased to welcome Laura Searcy and Cathy Haut to the Pediatric News Consultant Board.

Laura Searcy, MN, APRN, PPCNP-BC, is a pediatric nurse practitioner with more than 25 years’ experience in clinical practice, health policy, and advocacy with a focus on pediatric primary care, child and adolescent injury prevention, substance abuse prevention, and government affairs. Receiving her bachelor’s degree in nursing from the University of Florida in Gainesville, she earned her master’s degree in child health and pediatric nurse practitioner degrees from Emory University in Atlanta. Currently on the medical staff at WellStar Kennestone Regional Medical Center in Marietta, Ga., delivering care to newborns, Ms. Searcy has served as a preceptor and clinical instructor for all levels of nursing students at many institutions.

President of the National Association of Pediatric Nurse Practitioners (NAPNAP), Ms. Searcy previously served on the NAPNAP executive board as president-elect and health policy committee chair. She is a past Georgia NAPNAP chapter president and legislative chair as well as a cofounder of the Georgia Coalition of Advanced Practice Registered Nurses. A member of the American Association of Nurse Practitioners (AANP), Ms. Searcy received the 2014 AANP Nurse Practitioner State Award for Excellence from Georgia.

Widely recognized for her leadership skills, Ms. Searcy gained much of her governance experience serving three terms, including chair and vice chair, on the Cobb County Georgia Board of Education. The U.S. Secretary of Education appointed her to the Southeast Regional Advisement Committee, and the Georgia School Board Association appointed her to the National School Board Association Federal Relations Network. Ms. Searcy also has more than 12 years of nonprofit board experience, working with children’s advocacy centers and youth alcohol and drug-abuse prevention organizations.

Cathy Haut, DNP, CPNP-AC, CPNP-PC, CCRN, is a pediatric nurse practitioner who is the immediate past president of NAPNAP. She received her Master of Science degree as a neonatal clinical nurse specialist at the University of Maryland in the early 1990s and a post–master’s certificate as a pediatric nurse practitioner in 1997. Dr. Haut completed the Doctor of Nursing Practice program in 2010, focusing on pediatric nurses’ knowledge and attitudes toward palliative care. Board-certified in both primary and acute care, she has worked in pediatrics for more than 30 years, the past 19 years as a pediatric nurse practitioner. A fellow in the American Association of Colleges of Nurse’s Leadership for Academic Nursing Program, she holds a certificate in teaching in nursing education.

Dr. Haut works at Beacon Pediatrics, a large primary care practice in Rehoboth Beach, Del. She also works part time for Pediatrix Medical Group, serving the Pediatric Intensive Care Unit medical team at the Herman & Walter Samuelson Children’s Hospital at Sinai in Baltimore and serves as adjunct faculty at the University of Maryland School of Nursing, also in Baltimore.

The coeditor of a textbook, Lippincott Certification Review: Pediatric Acute Care Nurse Practitioner, Dr. Haut has published and presented on many clinical and professional topics. She has volunteered for different nursing organizations in a variety of positions, and has been an active member and leader of NAPNAP’s Maryland Chesapeake Chapter since 1996, serving as president in 2006-2007.

[email protected]

We are pleased to welcome Laura Searcy and Cathy Haut to the Pediatric News Consultant Board.

Laura Searcy, MN, APRN, PPCNP-BC, is a pediatric nurse practitioner with more than 25 years’ experience in clinical practice, health policy, and advocacy with a focus on pediatric primary care, child and adolescent injury prevention, substance abuse prevention, and government affairs. Receiving her bachelor’s degree in nursing from the University of Florida in Gainesville, she earned her master’s degree in child health and pediatric nurse practitioner degrees from Emory University in Atlanta. Currently on the medical staff at WellStar Kennestone Regional Medical Center in Marietta, Ga., delivering care to newborns, Ms. Searcy has served as a preceptor and clinical instructor for all levels of nursing students at many institutions.

President of the National Association of Pediatric Nurse Practitioners (NAPNAP), Ms. Searcy previously served on the NAPNAP executive board as president-elect and health policy committee chair. She is a past Georgia NAPNAP chapter president and legislative chair as well as a cofounder of the Georgia Coalition of Advanced Practice Registered Nurses. A member of the American Association of Nurse Practitioners (AANP), Ms. Searcy received the 2014 AANP Nurse Practitioner State Award for Excellence from Georgia.

Widely recognized for her leadership skills, Ms. Searcy gained much of her governance experience serving three terms, including chair and vice chair, on the Cobb County Georgia Board of Education. The U.S. Secretary of Education appointed her to the Southeast Regional Advisement Committee, and the Georgia School Board Association appointed her to the National School Board Association Federal Relations Network. Ms. Searcy also has more than 12 years of nonprofit board experience, working with children’s advocacy centers and youth alcohol and drug-abuse prevention organizations.

Cathy Haut, DNP, CPNP-AC, CPNP-PC, CCRN, is a pediatric nurse practitioner who is the immediate past president of NAPNAP. She received her Master of Science degree as a neonatal clinical nurse specialist at the University of Maryland in the early 1990s and a post–master’s certificate as a pediatric nurse practitioner in 1997. Dr. Haut completed the Doctor of Nursing Practice program in 2010, focusing on pediatric nurses’ knowledge and attitudes toward palliative care. Board-certified in both primary and acute care, she has worked in pediatrics for more than 30 years, the past 19 years as a pediatric nurse practitioner. A fellow in the American Association of Colleges of Nurse’s Leadership for Academic Nursing Program, she holds a certificate in teaching in nursing education.

Dr. Haut works at Beacon Pediatrics, a large primary care practice in Rehoboth Beach, Del. She also works part time for Pediatrix Medical Group, serving the Pediatric Intensive Care Unit medical team at the Herman & Walter Samuelson Children’s Hospital at Sinai in Baltimore and serves as adjunct faculty at the University of Maryland School of Nursing, also in Baltimore.

The coeditor of a textbook, Lippincott Certification Review: Pediatric Acute Care Nurse Practitioner, Dr. Haut has published and presented on many clinical and professional topics. She has volunteered for different nursing organizations in a variety of positions, and has been an active member and leader of NAPNAP’s Maryland Chesapeake Chapter since 1996, serving as president in 2006-2007.

[email protected]

We are pleased to welcome Laura Searcy and Cathy Haut to the Pediatric News Consultant Board.

Laura Searcy, MN, APRN, PPCNP-BC, is a pediatric nurse practitioner with more than 25 years’ experience in clinical practice, health policy, and advocacy with a focus on pediatric primary care, child and adolescent injury prevention, substance abuse prevention, and government affairs. Receiving her bachelor’s degree in nursing from the University of Florida in Gainesville, she earned her master’s degree in child health and pediatric nurse practitioner degrees from Emory University in Atlanta. Currently on the medical staff at WellStar Kennestone Regional Medical Center in Marietta, Ga., delivering care to newborns, Ms. Searcy has served as a preceptor and clinical instructor for all levels of nursing students at many institutions.

President of the National Association of Pediatric Nurse Practitioners (NAPNAP), Ms. Searcy previously served on the NAPNAP executive board as president-elect and health policy committee chair. She is a past Georgia NAPNAP chapter president and legislative chair as well as a cofounder of the Georgia Coalition of Advanced Practice Registered Nurses. A member of the American Association of Nurse Practitioners (AANP), Ms. Searcy received the 2014 AANP Nurse Practitioner State Award for Excellence from Georgia.

Widely recognized for her leadership skills, Ms. Searcy gained much of her governance experience serving three terms, including chair and vice chair, on the Cobb County Georgia Board of Education. The U.S. Secretary of Education appointed her to the Southeast Regional Advisement Committee, and the Georgia School Board Association appointed her to the National School Board Association Federal Relations Network. Ms. Searcy also has more than 12 years of nonprofit board experience, working with children’s advocacy centers and youth alcohol and drug-abuse prevention organizations.

Cathy Haut, DNP, CPNP-AC, CPNP-PC, CCRN, is a pediatric nurse practitioner who is the immediate past president of NAPNAP. She received her Master of Science degree as a neonatal clinical nurse specialist at the University of Maryland in the early 1990s and a post–master’s certificate as a pediatric nurse practitioner in 1997. Dr. Haut completed the Doctor of Nursing Practice program in 2010, focusing on pediatric nurses’ knowledge and attitudes toward palliative care. Board-certified in both primary and acute care, she has worked in pediatrics for more than 30 years, the past 19 years as a pediatric nurse practitioner. A fellow in the American Association of Colleges of Nurse’s Leadership for Academic Nursing Program, she holds a certificate in teaching in nursing education.

Dr. Haut works at Beacon Pediatrics, a large primary care practice in Rehoboth Beach, Del. She also works part time for Pediatrix Medical Group, serving the Pediatric Intensive Care Unit medical team at the Herman & Walter Samuelson Children’s Hospital at Sinai in Baltimore and serves as adjunct faculty at the University of Maryland School of Nursing, also in Baltimore.

The coeditor of a textbook, Lippincott Certification Review: Pediatric Acute Care Nurse Practitioner, Dr. Haut has published and presented on many clinical and professional topics. She has volunteered for different nursing organizations in a variety of positions, and has been an active member and leader of NAPNAP’s Maryland Chesapeake Chapter since 1996, serving as president in 2006-2007.

[email protected]

ROME – Continued dual-antiplatelet therapy beyond 12 months after coronary stenting is neither helped nor hindered by concomitant background optimal medical therapy, according to a secondary analysis of the landmark DAPT trial.

Numerous studies have shown that only 46%-66% of patients with stable ischemic heart disease are adherent to guideline-directed optimal medical therapy (OMT) with statins, beta-blockers, and ACE inhibitors or angiotensin receptor blockers. Yet until this new analysis from DAPT (the Dual Antiplatelet Therapy Study), the impact of OMT on the treatment effect of prolonged DAPT was unstudied, Charles D. Resor, MD, said at the annual congress of the European Society of Cardiology.

Bruce Jancin/Frontline Medical News

It was plausible that the treatment benefit of continued DAPT beyond 12 months after coronary stenting might be stunted by concomitant OMT, or alternatively that OMT and DAPT might exert synergistic effects in reducing the risk of ischemic events. As it turned out, neither of these possibilities turned out to be the case, according to Dr. Resor of Brigham and Women’s Hospital, Boston.

“I think OMT is underutilized, but while we would like physicians to emphasize OMT use in more cases, the decision to use DAPT beyond 12 months should be made irrespective of OMT use,” he said.

“That’s an important message for clinicians,” commented session cochair Keith A.A. Fox, MD, of the University of Edinburgh.

The landmark DAPT trial established that there is a significant benefit of continued dual-antiplatelet therapy beyond 12 months from coronary stenting in patients with stable ischemic heart disease (N Engl J Med. 2014 Dec 4;371:2155-66). Dr. Resor presented a secondary analysis of clinical outcomes in 11,643 study participants stratified by their OMT status as well as by whether they were randomized to dual-antiplatelet therapy or aspirin plus placebo.

Sixty-three percent of subjects were on OMT at enrollment. Adherence to OMT was high: At 30 months post stenting, 62% of participants remained on OMT.

Between 12 and 30 months after percutaneous coronary intervention, continued dual-antiplatelet therapy in patients also on OMT was associated with a 2.1% incidence of acute MI, a 36% reduction in risk, compared with the 3.3% rate in subjects on placebo plus OMT. In patients not on OMT, the MI rate was 2.2% in those on dual-antiplatelet therapy versus 5.2% with placebo, for a 59% relative risk reduction in the active treatment arm.

The rate of the composite endpoint of major adverse cardiovascular and cerebrovascular events in patients on dual-antiplatelet therapy and OMT was 4.2%, compared with a 5.0% rate in patients on placebo and OMT.

Moderate or severe bleeding, as measured by the Global Use of Strategies to Open Occluded Arteries (GUSTO) criteria occurred in 2.2% of patients on dual-antiplatelet therapy and OMT, compared with 1.0% in those on placebo plus OMT. In patients not on OMT, the bleeding rate was 2.8% in the dual-antiplatelet therapy group and 2.2% with placebo, a nonsignificant difference.

Overall, patients on OMT had significantly lower rates of acute MI than those not on OMT (2.7%, compared with 3.7%), as well as fewer major adverse cardiovascular and cerebrovascular events (4.6% versus 5.7%), and less moderate or severe bleeding (1.6%, compared with 2.5% in patients not on OMT). However, rates of stroke, stent thrombosis, and death didn’t differ between patients on OMT and those who were not.

“While the associations between OMT use and lower rates of MI and MACCE [major adverse cardiovascular and cerebrovascular events] were expected, the association with lower rates of moderate or severe bleeding was not; we suspect the lower bleeding risk is mostly due to some residual confounding,” according to Dr. Resor.

He reported having no financial conflicts of interest regarding the new secondary analysis of DAPT, which was sponsored by the Harvard Clinical Research Institute.

Simultaneously with Dr. Resor’s presentation, the new DAPT study analysis was published online (Circulation. 2016 Aug 30. doi: 10.1161/CIRCULATIONAHA.116.024531.)

[email protected]

ROME – Continued dual-antiplatelet therapy beyond 12 months after coronary stenting is neither helped nor hindered by concomitant background optimal medical therapy, according to a secondary analysis of the landmark DAPT trial.

Numerous studies have shown that only 46%-66% of patients with stable ischemic heart disease are adherent to guideline-directed optimal medical therapy (OMT) with statins, beta-blockers, and ACE inhibitors or angiotensin receptor blockers. Yet until this new analysis from DAPT (the Dual Antiplatelet Therapy Study), the impact of OMT on the treatment effect of prolonged DAPT was unstudied, Charles D. Resor, MD, said at the annual congress of the European Society of Cardiology.

Bruce Jancin/Frontline Medical News

It was plausible that the treatment benefit of continued DAPT beyond 12 months after coronary stenting might be stunted by concomitant OMT, or alternatively that OMT and DAPT might exert synergistic effects in reducing the risk of ischemic events. As it turned out, neither of these possibilities turned out to be the case, according to Dr. Resor of Brigham and Women’s Hospital, Boston.

“I think OMT is underutilized, but while we would like physicians to emphasize OMT use in more cases, the decision to use DAPT beyond 12 months should be made irrespective of OMT use,” he said.

“That’s an important message for clinicians,” commented session cochair Keith A.A. Fox, MD, of the University of Edinburgh.

The landmark DAPT trial established that there is a significant benefit of continued dual-antiplatelet therapy beyond 12 months from coronary stenting in patients with stable ischemic heart disease (N Engl J Med. 2014 Dec 4;371:2155-66). Dr. Resor presented a secondary analysis of clinical outcomes in 11,643 study participants stratified by their OMT status as well as by whether they were randomized to dual-antiplatelet therapy or aspirin plus placebo.

Sixty-three percent of subjects were on OMT at enrollment. Adherence to OMT was high: At 30 months post stenting, 62% of participants remained on OMT.

Between 12 and 30 months after percutaneous coronary intervention, continued dual-antiplatelet therapy in patients also on OMT was associated with a 2.1% incidence of acute MI, a 36% reduction in risk, compared with the 3.3% rate in subjects on placebo plus OMT. In patients not on OMT, the MI rate was 2.2% in those on dual-antiplatelet therapy versus 5.2% with placebo, for a 59% relative risk reduction in the active treatment arm.

The rate of the composite endpoint of major adverse cardiovascular and cerebrovascular events in patients on dual-antiplatelet therapy and OMT was 4.2%, compared with a 5.0% rate in patients on placebo and OMT.

Moderate or severe bleeding, as measured by the Global Use of Strategies to Open Occluded Arteries (GUSTO) criteria occurred in 2.2% of patients on dual-antiplatelet therapy and OMT, compared with 1.0% in those on placebo plus OMT. In patients not on OMT, the bleeding rate was 2.8% in the dual-antiplatelet therapy group and 2.2% with placebo, a nonsignificant difference.

Overall, patients on OMT had significantly lower rates of acute MI than those not on OMT (2.7%, compared with 3.7%), as well as fewer major adverse cardiovascular and cerebrovascular events (4.6% versus 5.7%), and less moderate or severe bleeding (1.6%, compared with 2.5% in patients not on OMT). However, rates of stroke, stent thrombosis, and death didn’t differ between patients on OMT and those who were not.

“While the associations between OMT use and lower rates of MI and MACCE [major adverse cardiovascular and cerebrovascular events] were expected, the association with lower rates of moderate or severe bleeding was not; we suspect the lower bleeding risk is mostly due to some residual confounding,” according to Dr. Resor.

He reported having no financial conflicts of interest regarding the new secondary analysis of DAPT, which was sponsored by the Harvard Clinical Research Institute.

Simultaneously with Dr. Resor’s presentation, the new DAPT study analysis was published online (Circulation. 2016 Aug 30. doi: 10.1161/CIRCULATIONAHA.116.024531.)

[email protected]

ROME – Continued dual-antiplatelet therapy beyond 12 months after coronary stenting is neither helped nor hindered by concomitant background optimal medical therapy, according to a secondary analysis of the landmark DAPT trial.

Numerous studies have shown that only 46%-66% of patients with stable ischemic heart disease are adherent to guideline-directed optimal medical therapy (OMT) with statins, beta-blockers, and ACE inhibitors or angiotensin receptor blockers. Yet until this new analysis from DAPT (the Dual Antiplatelet Therapy Study), the impact of OMT on the treatment effect of prolonged DAPT was unstudied, Charles D. Resor, MD, said at the annual congress of the European Society of Cardiology.

Bruce Jancin/Frontline Medical News

It was plausible that the treatment benefit of continued DAPT beyond 12 months after coronary stenting might be stunted by concomitant OMT, or alternatively that OMT and DAPT might exert synergistic effects in reducing the risk of ischemic events. As it turned out, neither of these possibilities turned out to be the case, according to Dr. Resor of Brigham and Women’s Hospital, Boston.

“I think OMT is underutilized, but while we would like physicians to emphasize OMT use in more cases, the decision to use DAPT beyond 12 months should be made irrespective of OMT use,” he said.

“That’s an important message for clinicians,” commented session cochair Keith A.A. Fox, MD, of the University of Edinburgh.

The landmark DAPT trial established that there is a significant benefit of continued dual-antiplatelet therapy beyond 12 months from coronary stenting in patients with stable ischemic heart disease (N Engl J Med. 2014 Dec 4;371:2155-66). Dr. Resor presented a secondary analysis of clinical outcomes in 11,643 study participants stratified by their OMT status as well as by whether they were randomized to dual-antiplatelet therapy or aspirin plus placebo.

Sixty-three percent of subjects were on OMT at enrollment. Adherence to OMT was high: At 30 months post stenting, 62% of participants remained on OMT.

Between 12 and 30 months after percutaneous coronary intervention, continued dual-antiplatelet therapy in patients also on OMT was associated with a 2.1% incidence of acute MI, a 36% reduction in risk, compared with the 3.3% rate in subjects on placebo plus OMT. In patients not on OMT, the MI rate was 2.2% in those on dual-antiplatelet therapy versus 5.2% with placebo, for a 59% relative risk reduction in the active treatment arm.

The rate of the composite endpoint of major adverse cardiovascular and cerebrovascular events in patients on dual-antiplatelet therapy and OMT was 4.2%, compared with a 5.0% rate in patients on placebo and OMT.

Moderate or severe bleeding, as measured by the Global Use of Strategies to Open Occluded Arteries (GUSTO) criteria occurred in 2.2% of patients on dual-antiplatelet therapy and OMT, compared with 1.0% in those on placebo plus OMT. In patients not on OMT, the bleeding rate was 2.8% in the dual-antiplatelet therapy group and 2.2% with placebo, a nonsignificant difference.

Overall, patients on OMT had significantly lower rates of acute MI than those not on OMT (2.7%, compared with 3.7%), as well as fewer major adverse cardiovascular and cerebrovascular events (4.6% versus 5.7%), and less moderate or severe bleeding (1.6%, compared with 2.5% in patients not on OMT). However, rates of stroke, stent thrombosis, and death didn’t differ between patients on OMT and those who were not.

“While the associations between OMT use and lower rates of MI and MACCE [major adverse cardiovascular and cerebrovascular events] were expected, the association with lower rates of moderate or severe bleeding was not; we suspect the lower bleeding risk is mostly due to some residual confounding,” according to Dr. Resor.

He reported having no financial conflicts of interest regarding the new secondary analysis of DAPT, which was sponsored by the Harvard Clinical Research Institute.

Simultaneously with Dr. Resor’s presentation, the new DAPT study analysis was published online (Circulation. 2016 Aug 30. doi: 10.1161/CIRCULATIONAHA.116.024531.)

[email protected]

IHS director Mary Smith recently issued an update on what’s been happening since the recent launch of “an aggressive strategy to improve the quality of care in the Great Plains area and across the country.”

The past 10 years have seen a new focus on quality improvement, she said, and IHS is working to enhance that with, for example, a system wide mock survey initiative at all 27 IHS hospitals to assess compliance with the Centers for Medicare & Medicaid Services (CMS) Conditions of Participation and readiness for reaccreditation.

Related: IHS and CMS Partner for Patient Safety Improvements

The IHS continues to face significant workforce challenges, including a chronic shortage of quality health care providers (HCPs), according to Smith. To that end, more than 2 dozen Commissioned Corps clinicians have been deployed to temporary placements in the Great Plains area hospitals with CMS findings. To attract more HCPs, the National Institutes of Health  has been helping IHS recruit more nurses into its clinical program; IHS is also revising position descriptions, using more comprehensive recruitment plans, raising pay, and instituting relocation pay for GS-12 and lower clinical positions and lower grades. IHS is also implementing a “stronger” search committee process and advertising vacancies more widely.

Another change is the expansion of tribal participation in filling vacant area director positions. Members of a tribe from each area will, for the first time, play a role at the outset of the hiring process, Smith said.

Related: Dangerous Staff Shortages in the IHS

The strategy also emphasizes bringing in health care quality expertise. This initiative began with the launch of a Hospital Engagement Network (HEN 2.0), which allows IHS hospitals to share strategies on how to reduce avoidable readmissions and hospital-acquired conditions.

The last priority area is to strengthen relationships with local and regional partners, like health care systems, colleges, and direct service hospitals. “Some of the most helpful expertise and the most effective leadership is right in the Tribal communities we work with every day,” Smith said. The “government-to-government relationship with Tribes is the foundation of our work at IHS.”

Related:  IHS Pilots Improved Version of Health Records

IHS director Mary Smith recently issued an update on what’s been happening since the recent launch of “an aggressive strategy to improve the quality of care in the Great Plains area and across the country.”

The past 10 years have seen a new focus on quality improvement, she said, and IHS is working to enhance that with, for example, a system wide mock survey initiative at all 27 IHS hospitals to assess compliance with the Centers for Medicare & Medicaid Services (CMS) Conditions of Participation and readiness for reaccreditation.

Related: IHS and CMS Partner for Patient Safety Improvements

The IHS continues to face significant workforce challenges, including a chronic shortage of quality health care providers (HCPs), according to Smith. To that end, more than 2 dozen Commissioned Corps clinicians have been deployed to temporary placements in the Great Plains area hospitals with CMS findings. To attract more HCPs, the National Institutes of Health  has been helping IHS recruit more nurses into its clinical program; IHS is also revising position descriptions, using more comprehensive recruitment plans, raising pay, and instituting relocation pay for GS-12 and lower clinical positions and lower grades. IHS is also implementing a “stronger” search committee process and advertising vacancies more widely.

Another change is the expansion of tribal participation in filling vacant area director positions. Members of a tribe from each area will, for the first time, play a role at the outset of the hiring process, Smith said.

Related: Dangerous Staff Shortages in the IHS

The strategy also emphasizes bringing in health care quality expertise. This initiative began with the launch of a Hospital Engagement Network (HEN 2.0), which allows IHS hospitals to share strategies on how to reduce avoidable readmissions and hospital-acquired conditions.

The last priority area is to strengthen relationships with local and regional partners, like health care systems, colleges, and direct service hospitals. “Some of the most helpful expertise and the most effective leadership is right in the Tribal communities we work with every day,” Smith said. The “government-to-government relationship with Tribes is the foundation of our work at IHS.”

Related:  IHS Pilots Improved Version of Health Records

IHS director Mary Smith recently issued an update on what’s been happening since the recent launch of “an aggressive strategy to improve the quality of care in the Great Plains area and across the country.”

The past 10 years have seen a new focus on quality improvement, she said, and IHS is working to enhance that with, for example, a system wide mock survey initiative at all 27 IHS hospitals to assess compliance with the Centers for Medicare & Medicaid Services (CMS) Conditions of Participation and readiness for reaccreditation.

Related: IHS and CMS Partner for Patient Safety Improvements

The IHS continues to face significant workforce challenges, including a chronic shortage of quality health care providers (HCPs), according to Smith. To that end, more than 2 dozen Commissioned Corps clinicians have been deployed to temporary placements in the Great Plains area hospitals with CMS findings. To attract more HCPs, the National Institutes of Health  has been helping IHS recruit more nurses into its clinical program; IHS is also revising position descriptions, using more comprehensive recruitment plans, raising pay, and instituting relocation pay for GS-12 and lower clinical positions and lower grades. IHS is also implementing a “stronger” search committee process and advertising vacancies more widely.

Another change is the expansion of tribal participation in filling vacant area director positions. Members of a tribe from each area will, for the first time, play a role at the outset of the hiring process, Smith said.

Related: Dangerous Staff Shortages in the IHS

The strategy also emphasizes bringing in health care quality expertise. This initiative began with the launch of a Hospital Engagement Network (HEN 2.0), which allows IHS hospitals to share strategies on how to reduce avoidable readmissions and hospital-acquired conditions.

The last priority area is to strengthen relationships with local and regional partners, like health care systems, colleges, and direct service hospitals. “Some of the most helpful expertise and the most effective leadership is right in the Tribal communities we work with every day,” Smith said. The “government-to-government relationship with Tribes is the foundation of our work at IHS.”

Related:  IHS Pilots Improved Version of Health Records

Diagrams showing a healthy

vein (left), thrombus formation

(middle), and a thrombus (right)

detaching from a vessel wall,

leading to thromboembolism.

Image by Moscow Institute

of Physics and Technology

Photoacoustic flow cytometry (PAFC) can provide real-time, non-invasive detection of emboli, according to research published in PLOS ONE.

Experiments in mice showed that PAFC can reveal emboli triggered by melanoma and medical procedures by detecting transient changes in blood absorption.

Investigators believe that by providing early embolus detection, PAFC could enable well-timed anticoagulant therapy and potentially prevent lethal complications.

For this study, the team used PAFC to monitor embolus formation in 4 groups of mice.

Two of the groups had melanoma. In one, the implanted tumor underwent compression. In the other, the investigators performed a surgical excision of the tumor.

The remaining 2 groups consisted of healthy mice. In one of these groups, mice had their limbs clamped to produce vessel stasis. In the other, the mice underwent surgery.

The investigators found that PAFC could detect a single embolus, and the method allowed them to distinguish between erythrocyte-rich and leukocyte/platelet-rich emboli.

They also observed a correlation between the presence of white emboli and melanoma.

The level of circulating emboli was significantly higher in the melanoma-bearing mice than in the healthy ones (P=0.0013).

However, the number of circulating emboli temporarily increased in the healthy mice during vessel stasis (P=0.033) and after surgical excisions (P=0.031).

The melanoma-bearing mice also experienced increases in the number of circulating emboli during tumor compression (P=0.013) and after tumor excision (P=0.012).

“We showed that it is possible to detect emboli in the bloodstream using photoacoustic flow cytometry,” said study author Alexander Melerzanov, PhD, of the Moscow Institute of Physics and Technology in Russia.

“PAFC may also be used to destroy blood clots, and we hope to work on this in our next experiments.”

Diagrams showing a healthy

vein (left), thrombus formation

(middle), and a thrombus (right)

detaching from a vessel wall,

leading to thromboembolism.

Image by Moscow Institute

of Physics and Technology

Photoacoustic flow cytometry (PAFC) can provide real-time, non-invasive detection of emboli, according to research published in PLOS ONE.

Experiments in mice showed that PAFC can reveal emboli triggered by melanoma and medical procedures by detecting transient changes in blood absorption.

Investigators believe that by providing early embolus detection, PAFC could enable well-timed anticoagulant therapy and potentially prevent lethal complications.

For this study, the team used PAFC to monitor embolus formation in 4 groups of mice.

Two of the groups had melanoma. In one, the implanted tumor underwent compression. In the other, the investigators performed a surgical excision of the tumor.

The remaining 2 groups consisted of healthy mice. In one of these groups, mice had their limbs clamped to produce vessel stasis. In the other, the mice underwent surgery.

The investigators found that PAFC could detect a single embolus, and the method allowed them to distinguish between erythrocyte-rich and leukocyte/platelet-rich emboli.

They also observed a correlation between the presence of white emboli and melanoma.

The level of circulating emboli was significantly higher in the melanoma-bearing mice than in the healthy ones (P=0.0013).

However, the number of circulating emboli temporarily increased in the healthy mice during vessel stasis (P=0.033) and after surgical excisions (P=0.031).

The melanoma-bearing mice also experienced increases in the number of circulating emboli during tumor compression (P=0.013) and after tumor excision (P=0.012).

“We showed that it is possible to detect emboli in the bloodstream using photoacoustic flow cytometry,” said study author Alexander Melerzanov, PhD, of the Moscow Institute of Physics and Technology in Russia.

“PAFC may also be used to destroy blood clots, and we hope to work on this in our next experiments.”

Diagrams showing a healthy

vein (left), thrombus formation

(middle), and a thrombus (right)

detaching from a vessel wall,

leading to thromboembolism.

Image by Moscow Institute

of Physics and Technology

Photoacoustic flow cytometry (PAFC) can provide real-time, non-invasive detection of emboli, according to research published in PLOS ONE.

Experiments in mice showed that PAFC can reveal emboli triggered by melanoma and medical procedures by detecting transient changes in blood absorption.

Investigators believe that by providing early embolus detection, PAFC could enable well-timed anticoagulant therapy and potentially prevent lethal complications.

For this study, the team used PAFC to monitor embolus formation in 4 groups of mice.

Two of the groups had melanoma. In one, the implanted tumor underwent compression. In the other, the investigators performed a surgical excision of the tumor.

The remaining 2 groups consisted of healthy mice. In one of these groups, mice had their limbs clamped to produce vessel stasis. In the other, the mice underwent surgery.

The investigators found that PAFC could detect a single embolus, and the method allowed them to distinguish between erythrocyte-rich and leukocyte/platelet-rich emboli.

They also observed a correlation between the presence of white emboli and melanoma.

The level of circulating emboli was significantly higher in the melanoma-bearing mice than in the healthy ones (P=0.0013).

However, the number of circulating emboli temporarily increased in the healthy mice during vessel stasis (P=0.033) and after surgical excisions (P=0.031).

The melanoma-bearing mice also experienced increases in the number of circulating emboli during tumor compression (P=0.013) and after tumor excision (P=0.012).

“We showed that it is possible to detect emboli in the bloodstream using photoacoustic flow cytometry,” said study author Alexander Melerzanov, PhD, of the Moscow Institute of Physics and Technology in Russia.

“PAFC may also be used to destroy blood clots, and we hope to work on this in our next experiments.”

Preparing capsules

for a clinical trial

Photo by Esther Dyson

Researchers have devised a method for predicting whether experimental drugs will fail clinical trials due to excessive toxicity.

They say the method, known as PrOCTOR, upends conventional wisdom about the criteria on which to evaluate new drugs’ safety.

Rather than exclusively examining molecular structure to determine viability, PrOCTOR combines a host of structural features and features related to how the drug binds to molecules in the body.

“We looked more broadly at drug molecule features that drug developers thought were unimportant in predicting drug safety in the past. Then, we let the data speak for itself,” said study author Olivier Elemento, PhD, of Weill Cornell Medicine in New York, New York.

Dr Elemento and his colleagues described PrOCTOR in Cell Chemical Biology.

PrOCTOR was inspired by an approach that baseball statisticians adopted to better predict which players would be successful offensively. Instead of relying on collective wisdom from baseball insiders, statisticians decided to use an objective numbers analysis to measure in-game productivity, a strategy known as “Moneyball.”

Similarly, Dr Elemento and his colleagues developed a computational method that analyzes data from 48 different features of a drug—from molecular weight to details about its target—to determine whether it would be safe for clinical use.

Using machine learning, the researchers trained PrOCTOR on drugs approved by the US Food and Drug Administration (FDA) as well as drugs that failed clinical trials due to toxicity problems.

Based on this information, the researchers created “PrOCTOR scores” that could help distinguish drugs approved by the FDA from those that failed for toxicity.

They tested PrOCTOR on hundreds of additional drugs approved in Europe and Japan and using side effect data on approved drugs collected by the FDA.

The researchers said PrOCTOR was able to accurately recognize toxic side effects that were a consequence of a drug’s chemical features and its target. Records revealing that many of these drugs had failed clinical trials supported PrOCTOR’s accuracy.

“We were able to find several features that led to a very predictive model,” Dr Elemento said. “Hopefully, this approach could be used to determine whether it’s worth pursuing a drug prior to starting human trials.”

Preparing capsules

for a clinical trial

Photo by Esther Dyson

Researchers have devised a method for predicting whether experimental drugs will fail clinical trials due to excessive toxicity.

They say the method, known as PrOCTOR, upends conventional wisdom about the criteria on which to evaluate new drugs’ safety.

Rather than exclusively examining molecular structure to determine viability, PrOCTOR combines a host of structural features and features related to how the drug binds to molecules in the body.

“We looked more broadly at drug molecule features that drug developers thought were unimportant in predicting drug safety in the past. Then, we let the data speak for itself,” said study author Olivier Elemento, PhD, of Weill Cornell Medicine in New York, New York.

Dr Elemento and his colleagues described PrOCTOR in Cell Chemical Biology.

PrOCTOR was inspired by an approach that baseball statisticians adopted to better predict which players would be successful offensively. Instead of relying on collective wisdom from baseball insiders, statisticians decided to use an objective numbers analysis to measure in-game productivity, a strategy known as “Moneyball.”

Similarly, Dr Elemento and his colleagues developed a computational method that analyzes data from 48 different features of a drug—from molecular weight to details about its target—to determine whether it would be safe for clinical use.

Using machine learning, the researchers trained PrOCTOR on drugs approved by the US Food and Drug Administration (FDA) as well as drugs that failed clinical trials due to toxicity problems.

Based on this information, the researchers created “PrOCTOR scores” that could help distinguish drugs approved by the FDA from those that failed for toxicity.

They tested PrOCTOR on hundreds of additional drugs approved in Europe and Japan and using side effect data on approved drugs collected by the FDA.

The researchers said PrOCTOR was able to accurately recognize toxic side effects that were a consequence of a drug’s chemical features and its target. Records revealing that many of these drugs had failed clinical trials supported PrOCTOR’s accuracy.

“We were able to find several features that led to a very predictive model,” Dr Elemento said. “Hopefully, this approach could be used to determine whether it’s worth pursuing a drug prior to starting human trials.”

Preparing capsules

for a clinical trial

Photo by Esther Dyson

Researchers have devised a method for predicting whether experimental drugs will fail clinical trials due to excessive toxicity.

They say the method, known as PrOCTOR, upends conventional wisdom about the criteria on which to evaluate new drugs’ safety.

Rather than exclusively examining molecular structure to determine viability, PrOCTOR combines a host of structural features and features related to how the drug binds to molecules in the body.

“We looked more broadly at drug molecule features that drug developers thought were unimportant in predicting drug safety in the past. Then, we let the data speak for itself,” said study author Olivier Elemento, PhD, of Weill Cornell Medicine in New York, New York.

Dr Elemento and his colleagues described PrOCTOR in Cell Chemical Biology.

PrOCTOR was inspired by an approach that baseball statisticians adopted to better predict which players would be successful offensively. Instead of relying on collective wisdom from baseball insiders, statisticians decided to use an objective numbers analysis to measure in-game productivity, a strategy known as “Moneyball.”

Similarly, Dr Elemento and his colleagues developed a computational method that analyzes data from 48 different features of a drug—from molecular weight to details about its target—to determine whether it would be safe for clinical use.

Using machine learning, the researchers trained PrOCTOR on drugs approved by the US Food and Drug Administration (FDA) as well as drugs that failed clinical trials due to toxicity problems.

Based on this information, the researchers created “PrOCTOR scores” that could help distinguish drugs approved by the FDA from those that failed for toxicity.

They tested PrOCTOR on hundreds of additional drugs approved in Europe and Japan and using side effect data on approved drugs collected by the FDA.

The researchers said PrOCTOR was able to accurately recognize toxic side effects that were a consequence of a drug’s chemical features and its target. Records revealing that many of these drugs had failed clinical trials supported PrOCTOR’s accuracy.

“We were able to find several features that led to a very predictive model,” Dr Elemento said. “Hopefully, this approach could be used to determine whether it’s worth pursuing a drug prior to starting human trials.”

Lab mouse

New research has revealed a potential treatment strategy for acute myeloid leukemia (AML) and other malignancies that show a preference for metabolizing fat over sugar.

The study suggests the protein prolyl hydroxylase 3 (PHD3) is a key regulator of fatty acid oxidation, and PHD3 expression is low in certain malignancies—particularly AML—but overexpressing PHD3 can have anticancer effects.

Researchers believe this finding might aid the development of therapies that work by starving tumors of their fuel.

“This really represents a new frontier in looking at the metabolism of cancer,” said study author Marcia Haigis, PhD, of Harvard Medical School in Boston, Massachusetts.

“Understanding the molecular handle of this pathway is the first step toward translating the basic work into therapy.”

Dr Haigis and her colleagues described the work in Molecular Cell.

The researchers knew that when cells run low on nutrients, they switch from sugar to fat as their fuel source to sustain function.

When cells have low energy, the protein AMPK targets the enzyme ACC to activate fat oxidation, which helps cells burn fats to make energy. However, when cells have enough resources, they seek to maintain energy balance.

Dr Haigis and her colleagues were searching for precisely how cells turn off fat oxidation and homed in on PHD3. Recent studies had suggested that PHD3 plays a part in cell metabolism, but,

until now, its precise role has remained unclear.

In a series of experiments, Dr Haigis’s team showed that PHD3 suppressed fat-burning by chemically modifying and activating ACC2—a version of the same enzyme responsible for keeping cellular fat-burning in check.

To determine PHD3’s role in cancer, the researchers combed through databases of all human cancers. The team theorized that sugar-craving malignancies would have high levels of PDH3, and cancers that relied on fat for their energy would have low levels.

The researchers found the lowest levels of PHD3 in AML, so they decided to examine the effects of restoring PHD3 in AML cells and a mouse model of the disease.

The experiments showed that restoring PHD3 expression reduces AML potency, and ACC2 is required for the inhibitory effects of PHD3. Overexpressing PHD3 limited fatty acid oxidation via regulation of ACC2, which decreased leukemia cell proliferation and enhanced survival in the mouse model of AML.

Dr Haigis noted that more basic research is needed before this work can move ahead to the clinic, as it’s still unclear why certain cancers depend on fat.

“What do fats provide to tumors that other fuels don’t?” Dr Haigis asked. “That’s one open question, and this is only the first chapter in the story.” 

Lab mouse

New research has revealed a potential treatment strategy for acute myeloid leukemia (AML) and other malignancies that show a preference for metabolizing fat over sugar.

The study suggests the protein prolyl hydroxylase 3 (PHD3) is a key regulator of fatty acid oxidation, and PHD3 expression is low in certain malignancies—particularly AML—but overexpressing PHD3 can have anticancer effects.

Researchers believe this finding might aid the development of therapies that work by starving tumors of their fuel.

“This really represents a new frontier in looking at the metabolism of cancer,” said study author Marcia Haigis, PhD, of Harvard Medical School in Boston, Massachusetts.

“Understanding the molecular handle of this pathway is the first step toward translating the basic work into therapy.”

Dr Haigis and her colleagues described the work in Molecular Cell.

The researchers knew that when cells run low on nutrients, they switch from sugar to fat as their fuel source to sustain function.

When cells have low energy, the protein AMPK targets the enzyme ACC to activate fat oxidation, which helps cells burn fats to make energy. However, when cells have enough resources, they seek to maintain energy balance.

Dr Haigis and her colleagues were searching for precisely how cells turn off fat oxidation and homed in on PHD3. Recent studies had suggested that PHD3 plays a part in cell metabolism, but,

until now, its precise role has remained unclear.

In a series of experiments, Dr Haigis’s team showed that PHD3 suppressed fat-burning by chemically modifying and activating ACC2—a version of the same enzyme responsible for keeping cellular fat-burning in check.

To determine PHD3’s role in cancer, the researchers combed through databases of all human cancers. The team theorized that sugar-craving malignancies would have high levels of PDH3, and cancers that relied on fat for their energy would have low levels.

The researchers found the lowest levels of PHD3 in AML, so they decided to examine the effects of restoring PHD3 in AML cells and a mouse model of the disease.

The experiments showed that restoring PHD3 expression reduces AML potency, and ACC2 is required for the inhibitory effects of PHD3. Overexpressing PHD3 limited fatty acid oxidation via regulation of ACC2, which decreased leukemia cell proliferation and enhanced survival in the mouse model of AML.

Dr Haigis noted that more basic research is needed before this work can move ahead to the clinic, as it’s still unclear why certain cancers depend on fat.

“What do fats provide to tumors that other fuels don’t?” Dr Haigis asked. “That’s one open question, and this is only the first chapter in the story.” 

Lab mouse

New research has revealed a potential treatment strategy for acute myeloid leukemia (AML) and other malignancies that show a preference for metabolizing fat over sugar.

The study suggests the protein prolyl hydroxylase 3 (PHD3) is a key regulator of fatty acid oxidation, and PHD3 expression is low in certain malignancies—particularly AML—but overexpressing PHD3 can have anticancer effects.

Researchers believe this finding might aid the development of therapies that work by starving tumors of their fuel.

“This really represents a new frontier in looking at the metabolism of cancer,” said study author Marcia Haigis, PhD, of Harvard Medical School in Boston, Massachusetts.

“Understanding the molecular handle of this pathway is the first step toward translating the basic work into therapy.”

Dr Haigis and her colleagues described the work in Molecular Cell.

The researchers knew that when cells run low on nutrients, they switch from sugar to fat as their fuel source to sustain function.

When cells have low energy, the protein AMPK targets the enzyme ACC to activate fat oxidation, which helps cells burn fats to make energy. However, when cells have enough resources, they seek to maintain energy balance.

Dr Haigis and her colleagues were searching for precisely how cells turn off fat oxidation and homed in on PHD3. Recent studies had suggested that PHD3 plays a part in cell metabolism, but,

until now, its precise role has remained unclear.

In a series of experiments, Dr Haigis’s team showed that PHD3 suppressed fat-burning by chemically modifying and activating ACC2—a version of the same enzyme responsible for keeping cellular fat-burning in check.

To determine PHD3’s role in cancer, the researchers combed through databases of all human cancers. The team theorized that sugar-craving malignancies would have high levels of PDH3, and cancers that relied on fat for their energy would have low levels.

The researchers found the lowest levels of PHD3 in AML, so they decided to examine the effects of restoring PHD3 in AML cells and a mouse model of the disease.

The experiments showed that restoring PHD3 expression reduces AML potency, and ACC2 is required for the inhibitory effects of PHD3. Overexpressing PHD3 limited fatty acid oxidation via regulation of ACC2, which decreased leukemia cell proliferation and enhanced survival in the mouse model of AML.

Dr Haigis noted that more basic research is needed before this work can move ahead to the clinic, as it’s still unclear why certain cancers depend on fat.

“What do fats provide to tumors that other fuels don’t?” Dr Haigis asked. “That’s one open question, and this is only the first chapter in the story.”