Crowd at the 2015 ASH

Annual Meeting

Photo courtesy of ASH

ORLANDO, FL—Results of a DFCI ALL Consortium trial have shown that adults with acute lymphoblastic leukemia (ALL) can be successfully and safely treated with a pediatric regimen using intensified pegylated asparaginase (PEG-ASP).

Investigators recently reported that young adults treated with native E coli asparaginase as part of their regimen had improved 4-year disease-free survival and overall survival (OS) rates.

Now, the team has shown it is possible to use PEG-ASP to improve young adult outcomes as well.

The investigators also described the toxicities with PEG-ASP and compared them to the prior DFCI ALL Consortium trial with native E coli asparaginase.

“[Wendy] Stock, years ago, analyzed young adult patients 16 to 20 based on whether or not they were treated on Children’s Cancer Group trials or CALGB trials,” said Daniel J. DeAngelo, MD, PhD, of the Dana-Farber Cancer Institute in Boston, Massachusetts.

“And what she reported was that there was a dramatic improvement in the disease- and event-free survival . . . . And since that publication and presentation at ASH several years ago, there’ve been a large number of us who’ve tried to adapt pediatric trials or pediatric-inspired trials for the treatment of young adults with acute lymphoblastic leukemia.”

The PEG-ASP DFCI ALL trial is one such effort. Dr DeAngelo discussed the results of this trial at the 2015 ASH Annual Meeting (abstract 80).

Patient population

Investigators enrolled 110 patients on the trial.

Patients had to be between 18 and 50 years of age, with untreated ALL and no history of secondary ALL. Patients with Burkitt’s lymphoma were excluded.

The patients’ median age was 32 (range, 18–50), 62% were male, 80% were white, and 85% were non-Hispanic. Eleven percent had central nervous system (CNS) status 2 or 3 prior to the initiation of chemotherapy.

Most (87%) had a performance status of 0 or 1, 82% had the B-cell and 18% the T-cell phenotype, 19% were Ph-positive, 6% had an MLL translocation (11q23), and 18% had other translocations.

Study design

Induction chemotherapy consisted of doxorubicin, prednisone, vincristine, PEG-ASP, and intrathecal therapy.

The first consolidation consisted of high-dose methotrexate followed by a BFM-like intensification and high-dose cytarabine, etoposide, and dexamethasone.

CNS prophylaxis included intrathecal chemotherapy and cranial irradiation.

The second consolidation consisted of eight 3-week courses of doxorubicin, vincristine, dexamethasone, 6-mercaptopurine, and 30 weeks of PEG-ASP.

The PEG-ASP was initially dosed at the pediatric level of 2500 IU/m² every 2 weeks.

“But due to some toxicity concerns in this treatment strategy—with specific emphasis on liver function abnormalities with hyperbilirubinemia, elevations of AST/ALT—we decided to amend the protocol and decrease the PEG dose from 2500 to 2000 and increase the interval from every 2 weeks to every 3 weeks,” Dr DeAngelo said.

Therefore, during this 30-week course, patients received 10 doses of PEG ASP as opposed to 15.

“We also went back and swapped out the PEG asparaginase during induction and reinserted native E coli to really ascertain comparative properties,” he said.

Maintenance therapy consisted of 3-week courses of vincristine, dexamethasone, methotrexate, and 6-mercaptopurine for 2 years from achievement of complete remission (CR).

During PEG-ASP therapy, patients received anticoagulation prophylaxis, preferably with low-molecular-weight heparin, as long as patients had a platelet count greater than 30,000/μL.

Results

Of the 110 patients enrolled, 65 received the higher dose of asparaginase, and 45 received the amended lower dose.

Ninety-one patients (89%) achieved a CR, 57 of whom received the higher dose of asparaginase and 34 the lower dose.

There were 2 induction deaths, both in the higher-dose group.

Twenty-one patients went on to transplant in CR1, 15 in the higher-dose group and 6 in the lower-dose group.

Twenty-three patients relapsed, 17 in the higher-dose group and 6 in the lower-dose group. Two of the relapses were CNS only.

Three patients died in remission, 2 in the higher-dose asparaginase group and 1 in the lower. And 3 patients died after stem cell transplant in CR, 2 in the higher-dose group and 1 in the lower.

At a median follow-up of 42.2 months, the 3-year disease-free survival for the entire cohort was 73%, and overall survival was 75%.

Subset analyses

The investigators performed subgroup analyses and came up with some “interesting observations,” Dr DeAngelo said.

Younger patients, ages 18 to 19 and 20 to 29, had a better OS than the older patients. The OS for younger patients is in the 80% to 85% range, “which is significantly better than the other patients in the 30 to 40 or 40 to 50 age groups,” Dr DeAngelo said.

Patients with T-cell ALL had a better OS than those with B-cell ALL and Ph-positive ALL, who had the worst OS of approximately 50%. The vast majority of Ph-negative patients were transplanted, and all received imatinib in addition to chemotherapy.

“[Patients with the T-cell phenotype] seemed to do particularly well on this strategy, which is something we showed in the last study as well, with an overall survival of 80%, compared to 70% for the B-cell Philadelphia-negative [patients],” Dr DeAngelo said.

He and his colleagues also found an association between OS and body mass index (BMI).

Obese or morbidly obese patients with a BMI of 30 or over had an OS of around 40%, while underweight or normal-weight patients had an OS of almost 90%, a “profound overall survival in the less-than-obese patients,” Dr DeAngelo said.

“And I think one of the things that is bringing down the curves is the obese,” he added, “which is a concern as the body mass index of the American population increases.”

Another discovery was that patients with minimal residual disease (MRD) of less than 10^-4 had better OS than those with a high MRD level.

After a single dose of PEG ASP during induction on day 4, asparagine was depleted for a median of 3 weeks. With a single dose of E coli asparaginase, on the other hand, asparagine is depleted for about a week.

Asparaginase levels during consolidation were “extraordinarily elevated” with the 2500 dose level of PEG-ASP compared to the lower dose level. Toxicity was much more manageable, however, as the dose was reduced, Dr DeAngelo said. And asparagine was still depleted throughout the 30 weeks, as per protocol.

Toxicity

The higher asparaginase dose group “surprisingly, had a very low rate of clinical pancreatitis,” Dr DeAngelo said.

At the higher asparaginase dose—2500 IU/m² every 2 weeks—66 patients experienced grade 3-5 adverse events: 30 (46%) febrile neutropenia, 1 (1%) pancreatitis, 19 (29%) AST, 34 (52%) ALT, 24 (36%) bilirubin, 19 (29%) thrombosis, 2 (3%) CNS hemorrhage, 3 (4%) hypersensitivity, and 4 (6%) osteonecrosis.

After the protocol amendment, “we saw a marked reduction in hyperbilirubinemia,” Dr DeAngelo said.

Grade 3–4 hyperbilirubinemia decreased from 36% to 7%, grade 3–4 ALT elevation decreased from 52% to 29%, and the rate of thrombosis decreased from 29% to 16%.

“Whether the latter decrease [thrombosis] was reflective of the decreased dose of asparaginase or the addition of anticoagulation, I can’t determine,”  Dr DeAngelo said, “but it seemed to reflect other studies.”

The investigators concluded that a dose-intensified pediatric regimen in adults is feasible, with an acceptable toxicity profile.

The team said this approach may translate to better survival for adults with ALL, with the exception of older adults and patients with a high BMI. PEG-ASP has increased toxicity in these patients.

The investigators recommend addressing the challenges that remain—psychosocial issues, practice patterns, and biology—with a unified approach and more cooperative group trials in young adults.

Crowd at the 2015 ASH

Annual Meeting

Photo courtesy of ASH

ORLANDO, FL—Results of a DFCI ALL Consortium trial have shown that adults with acute lymphoblastic leukemia (ALL) can be successfully and safely treated with a pediatric regimen using intensified pegylated asparaginase (PEG-ASP).

Investigators recently reported that young adults treated with native E coli asparaginase as part of their regimen had improved 4-year disease-free survival and overall survival (OS) rates.

Now, the team has shown it is possible to use PEG-ASP to improve young adult outcomes as well.

The investigators also described the toxicities with PEG-ASP and compared them to the prior DFCI ALL Consortium trial with native E coli asparaginase.

“[Wendy] Stock, years ago, analyzed young adult patients 16 to 20 based on whether or not they were treated on Children’s Cancer Group trials or CALGB trials,” said Daniel J. DeAngelo, MD, PhD, of the Dana-Farber Cancer Institute in Boston, Massachusetts.

“And what she reported was that there was a dramatic improvement in the disease- and event-free survival . . . . And since that publication and presentation at ASH several years ago, there’ve been a large number of us who’ve tried to adapt pediatric trials or pediatric-inspired trials for the treatment of young adults with acute lymphoblastic leukemia.”

The PEG-ASP DFCI ALL trial is one such effort. Dr DeAngelo discussed the results of this trial at the 2015 ASH Annual Meeting (abstract 80).

Patient population

Investigators enrolled 110 patients on the trial.

Patients had to be between 18 and 50 years of age, with untreated ALL and no history of secondary ALL. Patients with Burkitt’s lymphoma were excluded.

The patients’ median age was 32 (range, 18–50), 62% were male, 80% were white, and 85% were non-Hispanic. Eleven percent had central nervous system (CNS) status 2 or 3 prior to the initiation of chemotherapy.

Most (87%) had a performance status of 0 or 1, 82% had the B-cell and 18% the T-cell phenotype, 19% were Ph-positive, 6% had an MLL translocation (11q23), and 18% had other translocations.

Study design

Induction chemotherapy consisted of doxorubicin, prednisone, vincristine, PEG-ASP, and intrathecal therapy.

The first consolidation consisted of high-dose methotrexate followed by a BFM-like intensification and high-dose cytarabine, etoposide, and dexamethasone.

CNS prophylaxis included intrathecal chemotherapy and cranial irradiation.

The second consolidation consisted of eight 3-week courses of doxorubicin, vincristine, dexamethasone, 6-mercaptopurine, and 30 weeks of PEG-ASP.

The PEG-ASP was initially dosed at the pediatric level of 2500 IU/m² every 2 weeks.

“But due to some toxicity concerns in this treatment strategy—with specific emphasis on liver function abnormalities with hyperbilirubinemia, elevations of AST/ALT—we decided to amend the protocol and decrease the PEG dose from 2500 to 2000 and increase the interval from every 2 weeks to every 3 weeks,” Dr DeAngelo said.

Therefore, during this 30-week course, patients received 10 doses of PEG ASP as opposed to 15.

“We also went back and swapped out the PEG asparaginase during induction and reinserted native E coli to really ascertain comparative properties,” he said.

Maintenance therapy consisted of 3-week courses of vincristine, dexamethasone, methotrexate, and 6-mercaptopurine for 2 years from achievement of complete remission (CR).

During PEG-ASP therapy, patients received anticoagulation prophylaxis, preferably with low-molecular-weight heparin, as long as patients had a platelet count greater than 30,000/μL.

Results

Of the 110 patients enrolled, 65 received the higher dose of asparaginase, and 45 received the amended lower dose.

Ninety-one patients (89%) achieved a CR, 57 of whom received the higher dose of asparaginase and 34 the lower dose.

There were 2 induction deaths, both in the higher-dose group.

Twenty-one patients went on to transplant in CR1, 15 in the higher-dose group and 6 in the lower-dose group.

Twenty-three patients relapsed, 17 in the higher-dose group and 6 in the lower-dose group. Two of the relapses were CNS only.

Three patients died in remission, 2 in the higher-dose asparaginase group and 1 in the lower. And 3 patients died after stem cell transplant in CR, 2 in the higher-dose group and 1 in the lower.

At a median follow-up of 42.2 months, the 3-year disease-free survival for the entire cohort was 73%, and overall survival was 75%.

Subset analyses

The investigators performed subgroup analyses and came up with some “interesting observations,” Dr DeAngelo said.

Younger patients, ages 18 to 19 and 20 to 29, had a better OS than the older patients. The OS for younger patients is in the 80% to 85% range, “which is significantly better than the other patients in the 30 to 40 or 40 to 50 age groups,” Dr DeAngelo said.

Patients with T-cell ALL had a better OS than those with B-cell ALL and Ph-positive ALL, who had the worst OS of approximately 50%. The vast majority of Ph-negative patients were transplanted, and all received imatinib in addition to chemotherapy.

“[Patients with the T-cell phenotype] seemed to do particularly well on this strategy, which is something we showed in the last study as well, with an overall survival of 80%, compared to 70% for the B-cell Philadelphia-negative [patients],” Dr DeAngelo said.

He and his colleagues also found an association between OS and body mass index (BMI).

Obese or morbidly obese patients with a BMI of 30 or over had an OS of around 40%, while underweight or normal-weight patients had an OS of almost 90%, a “profound overall survival in the less-than-obese patients,” Dr DeAngelo said.

“And I think one of the things that is bringing down the curves is the obese,” he added, “which is a concern as the body mass index of the American population increases.”

Another discovery was that patients with minimal residual disease (MRD) of less than 10^-4 had better OS than those with a high MRD level.

After a single dose of PEG ASP during induction on day 4, asparagine was depleted for a median of 3 weeks. With a single dose of E coli asparaginase, on the other hand, asparagine is depleted for about a week.

Asparaginase levels during consolidation were “extraordinarily elevated” with the 2500 dose level of PEG-ASP compared to the lower dose level. Toxicity was much more manageable, however, as the dose was reduced, Dr DeAngelo said. And asparagine was still depleted throughout the 30 weeks, as per protocol.

Toxicity

The higher asparaginase dose group “surprisingly, had a very low rate of clinical pancreatitis,” Dr DeAngelo said.

At the higher asparaginase dose—2500 IU/m² every 2 weeks—66 patients experienced grade 3-5 adverse events: 30 (46%) febrile neutropenia, 1 (1%) pancreatitis, 19 (29%) AST, 34 (52%) ALT, 24 (36%) bilirubin, 19 (29%) thrombosis, 2 (3%) CNS hemorrhage, 3 (4%) hypersensitivity, and 4 (6%) osteonecrosis.

After the protocol amendment, “we saw a marked reduction in hyperbilirubinemia,” Dr DeAngelo said.

Grade 3–4 hyperbilirubinemia decreased from 36% to 7%, grade 3–4 ALT elevation decreased from 52% to 29%, and the rate of thrombosis decreased from 29% to 16%.

“Whether the latter decrease [thrombosis] was reflective of the decreased dose of asparaginase or the addition of anticoagulation, I can’t determine,”  Dr DeAngelo said, “but it seemed to reflect other studies.”

The investigators concluded that a dose-intensified pediatric regimen in adults is feasible, with an acceptable toxicity profile.

The team said this approach may translate to better survival for adults with ALL, with the exception of older adults and patients with a high BMI. PEG-ASP has increased toxicity in these patients.

The investigators recommend addressing the challenges that remain—psychosocial issues, practice patterns, and biology—with a unified approach and more cooperative group trials in young adults.

Crowd at the 2015 ASH

Annual Meeting

Photo courtesy of ASH

ORLANDO, FL—Results of a DFCI ALL Consortium trial have shown that adults with acute lymphoblastic leukemia (ALL) can be successfully and safely treated with a pediatric regimen using intensified pegylated asparaginase (PEG-ASP).

Investigators recently reported that young adults treated with native E coli asparaginase as part of their regimen had improved 4-year disease-free survival and overall survival (OS) rates.

Now, the team has shown it is possible to use PEG-ASP to improve young adult outcomes as well.

The investigators also described the toxicities with PEG-ASP and compared them to the prior DFCI ALL Consortium trial with native E coli asparaginase.

“[Wendy] Stock, years ago, analyzed young adult patients 16 to 20 based on whether or not they were treated on Children’s Cancer Group trials or CALGB trials,” said Daniel J. DeAngelo, MD, PhD, of the Dana-Farber Cancer Institute in Boston, Massachusetts.

“And what she reported was that there was a dramatic improvement in the disease- and event-free survival . . . . And since that publication and presentation at ASH several years ago, there’ve been a large number of us who’ve tried to adapt pediatric trials or pediatric-inspired trials for the treatment of young adults with acute lymphoblastic leukemia.”

The PEG-ASP DFCI ALL trial is one such effort. Dr DeAngelo discussed the results of this trial at the 2015 ASH Annual Meeting (abstract 80).

Patient population

Investigators enrolled 110 patients on the trial.

Patients had to be between 18 and 50 years of age, with untreated ALL and no history of secondary ALL. Patients with Burkitt’s lymphoma were excluded.

The patients’ median age was 32 (range, 18–50), 62% were male, 80% were white, and 85% were non-Hispanic. Eleven percent had central nervous system (CNS) status 2 or 3 prior to the initiation of chemotherapy.

Most (87%) had a performance status of 0 or 1, 82% had the B-cell and 18% the T-cell phenotype, 19% were Ph-positive, 6% had an MLL translocation (11q23), and 18% had other translocations.

Study design

Induction chemotherapy consisted of doxorubicin, prednisone, vincristine, PEG-ASP, and intrathecal therapy.

The first consolidation consisted of high-dose methotrexate followed by a BFM-like intensification and high-dose cytarabine, etoposide, and dexamethasone.

CNS prophylaxis included intrathecal chemotherapy and cranial irradiation.

The second consolidation consisted of eight 3-week courses of doxorubicin, vincristine, dexamethasone, 6-mercaptopurine, and 30 weeks of PEG-ASP.

The PEG-ASP was initially dosed at the pediatric level of 2500 IU/m² every 2 weeks.

“But due to some toxicity concerns in this treatment strategy—with specific emphasis on liver function abnormalities with hyperbilirubinemia, elevations of AST/ALT—we decided to amend the protocol and decrease the PEG dose from 2500 to 2000 and increase the interval from every 2 weeks to every 3 weeks,” Dr DeAngelo said.

Therefore, during this 30-week course, patients received 10 doses of PEG ASP as opposed to 15.

“We also went back and swapped out the PEG asparaginase during induction and reinserted native E coli to really ascertain comparative properties,” he said.

Maintenance therapy consisted of 3-week courses of vincristine, dexamethasone, methotrexate, and 6-mercaptopurine for 2 years from achievement of complete remission (CR).

During PEG-ASP therapy, patients received anticoagulation prophylaxis, preferably with low-molecular-weight heparin, as long as patients had a platelet count greater than 30,000/μL.

Results

Of the 110 patients enrolled, 65 received the higher dose of asparaginase, and 45 received the amended lower dose.

Ninety-one patients (89%) achieved a CR, 57 of whom received the higher dose of asparaginase and 34 the lower dose.

There were 2 induction deaths, both in the higher-dose group.

Twenty-one patients went on to transplant in CR1, 15 in the higher-dose group and 6 in the lower-dose group.

Twenty-three patients relapsed, 17 in the higher-dose group and 6 in the lower-dose group. Two of the relapses were CNS only.

Three patients died in remission, 2 in the higher-dose asparaginase group and 1 in the lower. And 3 patients died after stem cell transplant in CR, 2 in the higher-dose group and 1 in the lower.

At a median follow-up of 42.2 months, the 3-year disease-free survival for the entire cohort was 73%, and overall survival was 75%.

Subset analyses

The investigators performed subgroup analyses and came up with some “interesting observations,” Dr DeAngelo said.

Younger patients, ages 18 to 19 and 20 to 29, had a better OS than the older patients. The OS for younger patients is in the 80% to 85% range, “which is significantly better than the other patients in the 30 to 40 or 40 to 50 age groups,” Dr DeAngelo said.

Patients with T-cell ALL had a better OS than those with B-cell ALL and Ph-positive ALL, who had the worst OS of approximately 50%. The vast majority of Ph-negative patients were transplanted, and all received imatinib in addition to chemotherapy.

“[Patients with the T-cell phenotype] seemed to do particularly well on this strategy, which is something we showed in the last study as well, with an overall survival of 80%, compared to 70% for the B-cell Philadelphia-negative [patients],” Dr DeAngelo said.

He and his colleagues also found an association between OS and body mass index (BMI).

Obese or morbidly obese patients with a BMI of 30 or over had an OS of around 40%, while underweight or normal-weight patients had an OS of almost 90%, a “profound overall survival in the less-than-obese patients,” Dr DeAngelo said.

“And I think one of the things that is bringing down the curves is the obese,” he added, “which is a concern as the body mass index of the American population increases.”

Another discovery was that patients with minimal residual disease (MRD) of less than 10^-4 had better OS than those with a high MRD level.

After a single dose of PEG ASP during induction on day 4, asparagine was depleted for a median of 3 weeks. With a single dose of E coli asparaginase, on the other hand, asparagine is depleted for about a week.

Asparaginase levels during consolidation were “extraordinarily elevated” with the 2500 dose level of PEG-ASP compared to the lower dose level. Toxicity was much more manageable, however, as the dose was reduced, Dr DeAngelo said. And asparagine was still depleted throughout the 30 weeks, as per protocol.

Toxicity

The higher asparaginase dose group “surprisingly, had a very low rate of clinical pancreatitis,” Dr DeAngelo said.

At the higher asparaginase dose—2500 IU/m² every 2 weeks—66 patients experienced grade 3-5 adverse events: 30 (46%) febrile neutropenia, 1 (1%) pancreatitis, 19 (29%) AST, 34 (52%) ALT, 24 (36%) bilirubin, 19 (29%) thrombosis, 2 (3%) CNS hemorrhage, 3 (4%) hypersensitivity, and 4 (6%) osteonecrosis.

After the protocol amendment, “we saw a marked reduction in hyperbilirubinemia,” Dr DeAngelo said.

Grade 3–4 hyperbilirubinemia decreased from 36% to 7%, grade 3–4 ALT elevation decreased from 52% to 29%, and the rate of thrombosis decreased from 29% to 16%.

“Whether the latter decrease [thrombosis] was reflective of the decreased dose of asparaginase or the addition of anticoagulation, I can’t determine,”  Dr DeAngelo said, “but it seemed to reflect other studies.”

The investigators concluded that a dose-intensified pediatric regimen in adults is feasible, with an acceptable toxicity profile.

The team said this approach may translate to better survival for adults with ALL, with the exception of older adults and patients with a high BMI. PEG-ASP has increased toxicity in these patients.

The investigators recommend addressing the challenges that remain—psychosocial issues, practice patterns, and biology—with a unified approach and more cooperative group trials in young adults.

Preparing pills for a clinical trial

Photo by Esther Dyson

A new study suggests that, in recent years, there has been a decrease in clinical trials funded by the National Institutes of Health (NIH) but an increase in trials with funding from other sources.

Researchers looked at trials newly registered on ClinicalTrials.gov and observed a substantial increase in trial listings from 2006 through 2014.

During that time period, the number of NIH-funded trials declined, but the number of trials funded by other US federal agencies, industry, and other groups (such as universities and organizations) increased.

Stephan Ehrhardt, MD, of Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, and his colleagues conducted this study and recounted their findings in a letter to JAMA.

The researchers downloaded data from ClinicalTrials.gov, searched for “interventional study” and obtained counts of newly registered trials by funder type: “NIH,” “industry,” “other US federal agency,” or “all others (individuals, universities, organizations).”

According to the “first received” date (when trials were first registered with ClinicalTrials.gov), the number of newly registered trials increased from 9321 in 2006 to 18,400 in 2014 (97.4%).

During the same period, the number of industry-funded trials increased from 4585 to 6550 (42.9%), and the number of NIH-funded trials decreased from 1376 to 1048 (23.8%).

The number of trials funded by other US federal agencies increased from 263 to 339 (28.9%), and the number of trials funded by “all others” increased from 3240 to 10,597 (227.1%).

The researchers also examined the data according to the trial start date and observed similar patterns. They found the total number of trials increased from 9208 in 2006 to 14,618 in 2014 (58.8%).

The number of industry-funded trials increased from 4516 to 5274 (36.1%), and the number of NIH-funded trials decreased from 1189 to 873 (26.6%).

The number of trials funded by other US federal agencies increased from 229 to 292 (27.5%), and the number of trials funded by “all others” increased from 3397 to 8295 (144.2%).

Dr Ehrhardt said he believes the decline in NIH-funded studies can be traced to 2 things: flat NIH funding (the 2014 budget was 14% less than in 2006, after adjusting for inflation) and greater competition for these limited dollars from other, relatively new research areas such as genomic research or personalized medicine studies.

Preparing pills for a clinical trial

Photo by Esther Dyson

A new study suggests that, in recent years, there has been a decrease in clinical trials funded by the National Institutes of Health (NIH) but an increase in trials with funding from other sources.

Researchers looked at trials newly registered on ClinicalTrials.gov and observed a substantial increase in trial listings from 2006 through 2014.

During that time period, the number of NIH-funded trials declined, but the number of trials funded by other US federal agencies, industry, and other groups (such as universities and organizations) increased.

Stephan Ehrhardt, MD, of Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, and his colleagues conducted this study and recounted their findings in a letter to JAMA.

The researchers downloaded data from ClinicalTrials.gov, searched for “interventional study” and obtained counts of newly registered trials by funder type: “NIH,” “industry,” “other US federal agency,” or “all others (individuals, universities, organizations).”

According to the “first received” date (when trials were first registered with ClinicalTrials.gov), the number of newly registered trials increased from 9321 in 2006 to 18,400 in 2014 (97.4%).

During the same period, the number of industry-funded trials increased from 4585 to 6550 (42.9%), and the number of NIH-funded trials decreased from 1376 to 1048 (23.8%).

The number of trials funded by other US federal agencies increased from 263 to 339 (28.9%), and the number of trials funded by “all others” increased from 3240 to 10,597 (227.1%).

The researchers also examined the data according to the trial start date and observed similar patterns. They found the total number of trials increased from 9208 in 2006 to 14,618 in 2014 (58.8%).

The number of industry-funded trials increased from 4516 to 5274 (36.1%), and the number of NIH-funded trials decreased from 1189 to 873 (26.6%).

The number of trials funded by other US federal agencies increased from 229 to 292 (27.5%), and the number of trials funded by “all others” increased from 3397 to 8295 (144.2%).

Dr Ehrhardt said he believes the decline in NIH-funded studies can be traced to 2 things: flat NIH funding (the 2014 budget was 14% less than in 2006, after adjusting for inflation) and greater competition for these limited dollars from other, relatively new research areas such as genomic research or personalized medicine studies.

Preparing pills for a clinical trial

Photo by Esther Dyson

A new study suggests that, in recent years, there has been a decrease in clinical trials funded by the National Institutes of Health (NIH) but an increase in trials with funding from other sources.

Researchers looked at trials newly registered on ClinicalTrials.gov and observed a substantial increase in trial listings from 2006 through 2014.

During that time period, the number of NIH-funded trials declined, but the number of trials funded by other US federal agencies, industry, and other groups (such as universities and organizations) increased.

Stephan Ehrhardt, MD, of Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, and his colleagues conducted this study and recounted their findings in a letter to JAMA.

The researchers downloaded data from ClinicalTrials.gov, searched for “interventional study” and obtained counts of newly registered trials by funder type: “NIH,” “industry,” “other US federal agency,” or “all others (individuals, universities, organizations).”

According to the “first received” date (when trials were first registered with ClinicalTrials.gov), the number of newly registered trials increased from 9321 in 2006 to 18,400 in 2014 (97.4%).

During the same period, the number of industry-funded trials increased from 4585 to 6550 (42.9%), and the number of NIH-funded trials decreased from 1376 to 1048 (23.8%).

The number of trials funded by other US federal agencies increased from 263 to 339 (28.9%), and the number of trials funded by “all others” increased from 3240 to 10,597 (227.1%).

The researchers also examined the data according to the trial start date and observed similar patterns. They found the total number of trials increased from 9208 in 2006 to 14,618 in 2014 (58.8%).

The number of industry-funded trials increased from 4516 to 5274 (36.1%), and the number of NIH-funded trials decreased from 1189 to 873 (26.6%).

The number of trials funded by other US federal agencies increased from 229 to 292 (27.5%), and the number of trials funded by “all others” increased from 3397 to 8295 (144.2%).

Dr Ehrhardt said he believes the decline in NIH-funded studies can be traced to 2 things: flat NIH funding (the 2014 budget was 14% less than in 2006, after adjusting for inflation) and greater competition for these limited dollars from other, relatively new research areas such as genomic research or personalized medicine studies.

James Merlino, MD, president and CMO of Press Ganey's strategic consulting division, wants to convince physicians around the country that hospital medicine is good healthcare as a whole.

“[Hospitalists] are the holistic scorekeepers for a variety of medical conditions that a lot of physicians don’t understand and don’t treat very well,” says Dr. Merlino, whose company supports healthcare providers in improving the patient experience. “We know that when their model is allowed to foster, quality improves [and] safety improves. It’s a model that needs to be embraced so we can deliver better care for patients.”

Dr. Merlino recently talked with The Hospitalist:

Question: You say you’ve seen some specialists and primary care physicians disrespect hospitalists. Why do you believe that occurs?

Answer: It’s a relatively new model, and physicians who have patients in the hospital, nonhospitalists, don’t like to give up the autonomy and the control they feel they have or the responsibility they have to care for patients. The hospitalist model challenges that.

Q: How does healthcare develop a culture that prizes hospitalists and encourages teamwork?

A: Number one, people have to call it out and talk about it. What surprised me in one hospital I visited was [that] the hospitalists did not elevate the issue to leadership. The second thing that relates to changing physician culture is accountability of leadership. When medical staff leaders find out about this type of behavior, it must be addressed.

Q: Why does the challenge persist?

A: It’s leaders stepping up and holding people accountable for their actions. Leaders sometimes have a tendency to ignore behavior problems. When issues like lack of professionalism are identified, then medical leadership really needs to step in and deal with the individuals who are creating the problem. That is a gap in healthcare.

Q: What stops leaders from being accountable?

A: The problem is that physician leaders and other leaders tend to shy away from controversial problems. Pushing into a medical staff issue like this is complicated and difficult. Physicians are the engines of your organization. Leaders are working very hard to keep the medical staff in a steady state … and often there’s a reluctance to push into behavioral problems. TH

Visit our website for more information on multidisciplinary care.

James Merlino, MD, president and CMO of Press Ganey's strategic consulting division, wants to convince physicians around the country that hospital medicine is good healthcare as a whole.

“[Hospitalists] are the holistic scorekeepers for a variety of medical conditions that a lot of physicians don’t understand and don’t treat very well,” says Dr. Merlino, whose company supports healthcare providers in improving the patient experience. “We know that when their model is allowed to foster, quality improves [and] safety improves. It’s a model that needs to be embraced so we can deliver better care for patients.”

Dr. Merlino recently talked with The Hospitalist:

Question: You say you’ve seen some specialists and primary care physicians disrespect hospitalists. Why do you believe that occurs?

Answer: It’s a relatively new model, and physicians who have patients in the hospital, nonhospitalists, don’t like to give up the autonomy and the control they feel they have or the responsibility they have to care for patients. The hospitalist model challenges that.

Q: How does healthcare develop a culture that prizes hospitalists and encourages teamwork?

A: Number one, people have to call it out and talk about it. What surprised me in one hospital I visited was [that] the hospitalists did not elevate the issue to leadership. The second thing that relates to changing physician culture is accountability of leadership. When medical staff leaders find out about this type of behavior, it must be addressed.

Q: Why does the challenge persist?

A: It’s leaders stepping up and holding people accountable for their actions. Leaders sometimes have a tendency to ignore behavior problems. When issues like lack of professionalism are identified, then medical leadership really needs to step in and deal with the individuals who are creating the problem. That is a gap in healthcare.

Q: What stops leaders from being accountable?

A: The problem is that physician leaders and other leaders tend to shy away from controversial problems. Pushing into a medical staff issue like this is complicated and difficult. Physicians are the engines of your organization. Leaders are working very hard to keep the medical staff in a steady state … and often there’s a reluctance to push into behavioral problems. TH

Visit our website for more information on multidisciplinary care.

James Merlino, MD, president and CMO of Press Ganey's strategic consulting division, wants to convince physicians around the country that hospital medicine is good healthcare as a whole.

“[Hospitalists] are the holistic scorekeepers for a variety of medical conditions that a lot of physicians don’t understand and don’t treat very well,” says Dr. Merlino, whose company supports healthcare providers in improving the patient experience. “We know that when their model is allowed to foster, quality improves [and] safety improves. It’s a model that needs to be embraced so we can deliver better care for patients.”

Dr. Merlino recently talked with The Hospitalist:

Question: You say you’ve seen some specialists and primary care physicians disrespect hospitalists. Why do you believe that occurs?

Answer: It’s a relatively new model, and physicians who have patients in the hospital, nonhospitalists, don’t like to give up the autonomy and the control they feel they have or the responsibility they have to care for patients. The hospitalist model challenges that.

Q: How does healthcare develop a culture that prizes hospitalists and encourages teamwork?

A: Number one, people have to call it out and talk about it. What surprised me in one hospital I visited was [that] the hospitalists did not elevate the issue to leadership. The second thing that relates to changing physician culture is accountability of leadership. When medical staff leaders find out about this type of behavior, it must be addressed.

Q: Why does the challenge persist?

A: It’s leaders stepping up and holding people accountable for their actions. Leaders sometimes have a tendency to ignore behavior problems. When issues like lack of professionalism are identified, then medical leadership really needs to step in and deal with the individuals who are creating the problem. That is a gap in healthcare.

Q: What stops leaders from being accountable?

A: The problem is that physician leaders and other leaders tend to shy away from controversial problems. Pushing into a medical staff issue like this is complicated and difficult. Physicians are the engines of your organization. Leaders are working very hard to keep the medical staff in a steady state … and often there’s a reluctance to push into behavioral problems. TH

Visit our website for more information on multidisciplinary care.

People diagnosed with unipolar depression have a higher chance of developing mania or bipolar disorder if they’ve previously been treated with antidepressants, a new study shows (BMJ Open. 2015 Dec 15. doi: 10.1136/bmjopen-2015-008341).

“Our findings demonstrate a significant association between antidepressant therapy in patients with unipolar depression and an increased incidence of mania,” Dr. Rashmi Patel of King’s College, London, and his associates reported in the study. Moreover, the association remains significant after adjusting for both age and gender, they wrote.

©g-stockstudio/thinkstockphotos.com

Dr. Patel and his associates conducted a retrospective cohort study on 21,012 individuals aged 16 to 65 years – all of whom were diagnosed with depression and had no previous diagnosis of mania or bipolar disorder between April 1, 2006, and March 31, 2013 – from the South London and Maudsley National Health Service Foundation Trust. Clinical data on subjects’ medical history, mental state examinations, diagnostic formulations, and management plans were collected. Subjects also were classified as having had “prior antidepressant therapy” if there was “documentation of antidepressant treatment prior to the date of diagnosis of depression.” Follow-ups occurred through March 31, 2014, and the primary outcome was a diagnosis of mania or bipolar disorder during that period.

Results showed an incidence rate of 10.9 per 1,000 person-years of mania or bipolar disorder across the entire study population. The lowest incidence, 8.3 per 1,000 person-years, was in the 56-65 years age cohort, while those in the 26-35 years age cohort had the highest incidence rate – 12.3 per 1,000 person-years (P = .004).

Subjects with prior antidepressant use saw significant increases in incidence rates of mania or bipolar disorder, depending on which antidepressant they were taking. Those on tricyclics (4.7% of subjects with previous antidepressant treatment) had a 13.1 per 1,000 person-years incidence rate, while those taking trazodone (0.8%) had a 19.1 per 1,000 person-years incidence rate (P = .09 and P = .03, respectively). The most commonly used antidepressants were selective serotonin reuptake inhibitors (35.5%), which yielded an incidence rate of 13.2 per 1,000 person-years.

“The association of antidepressant therapy with mania demonstrated in the present and previous studies highlights the importance of considering whether an individual who presents with depression could be at risk of future episodes of mania,” the authors concluded. They concluded that the findings reinforce the “ongoing need to develop better ways to predict future risk of mania in people with no prior history of bipolar disorder who present with an episode of depression.”

The study was supported by the U.K. Medical Research Council Clinical Research Training Fellowship. Neither Dr. Patel nor his associates reported relevant financial disclosures.

[email protected]

People diagnosed with unipolar depression have a higher chance of developing mania or bipolar disorder if they’ve previously been treated with antidepressants, a new study shows (BMJ Open. 2015 Dec 15. doi: 10.1136/bmjopen-2015-008341).

“Our findings demonstrate a significant association between antidepressant therapy in patients with unipolar depression and an increased incidence of mania,” Dr. Rashmi Patel of King’s College, London, and his associates reported in the study. Moreover, the association remains significant after adjusting for both age and gender, they wrote.

©g-stockstudio/thinkstockphotos.com

Dr. Patel and his associates conducted a retrospective cohort study on 21,012 individuals aged 16 to 65 years – all of whom were diagnosed with depression and had no previous diagnosis of mania or bipolar disorder between April 1, 2006, and March 31, 2013 – from the South London and Maudsley National Health Service Foundation Trust. Clinical data on subjects’ medical history, mental state examinations, diagnostic formulations, and management plans were collected. Subjects also were classified as having had “prior antidepressant therapy” if there was “documentation of antidepressant treatment prior to the date of diagnosis of depression.” Follow-ups occurred through March 31, 2014, and the primary outcome was a diagnosis of mania or bipolar disorder during that period.

Results showed an incidence rate of 10.9 per 1,000 person-years of mania or bipolar disorder across the entire study population. The lowest incidence, 8.3 per 1,000 person-years, was in the 56-65 years age cohort, while those in the 26-35 years age cohort had the highest incidence rate – 12.3 per 1,000 person-years (P = .004).

Subjects with prior antidepressant use saw significant increases in incidence rates of mania or bipolar disorder, depending on which antidepressant they were taking. Those on tricyclics (4.7% of subjects with previous antidepressant treatment) had a 13.1 per 1,000 person-years incidence rate, while those taking trazodone (0.8%) had a 19.1 per 1,000 person-years incidence rate (P = .09 and P = .03, respectively). The most commonly used antidepressants were selective serotonin reuptake inhibitors (35.5%), which yielded an incidence rate of 13.2 per 1,000 person-years.

“The association of antidepressant therapy with mania demonstrated in the present and previous studies highlights the importance of considering whether an individual who presents with depression could be at risk of future episodes of mania,” the authors concluded. They concluded that the findings reinforce the “ongoing need to develop better ways to predict future risk of mania in people with no prior history of bipolar disorder who present with an episode of depression.”

The study was supported by the U.K. Medical Research Council Clinical Research Training Fellowship. Neither Dr. Patel nor his associates reported relevant financial disclosures.

[email protected]

People diagnosed with unipolar depression have a higher chance of developing mania or bipolar disorder if they’ve previously been treated with antidepressants, a new study shows (BMJ Open. 2015 Dec 15. doi: 10.1136/bmjopen-2015-008341).

“Our findings demonstrate a significant association between antidepressant therapy in patients with unipolar depression and an increased incidence of mania,” Dr. Rashmi Patel of King’s College, London, and his associates reported in the study. Moreover, the association remains significant after adjusting for both age and gender, they wrote.

©g-stockstudio/thinkstockphotos.com

Dr. Patel and his associates conducted a retrospective cohort study on 21,012 individuals aged 16 to 65 years – all of whom were diagnosed with depression and had no previous diagnosis of mania or bipolar disorder between April 1, 2006, and March 31, 2013 – from the South London and Maudsley National Health Service Foundation Trust. Clinical data on subjects’ medical history, mental state examinations, diagnostic formulations, and management plans were collected. Subjects also were classified as having had “prior antidepressant therapy” if there was “documentation of antidepressant treatment prior to the date of diagnosis of depression.” Follow-ups occurred through March 31, 2014, and the primary outcome was a diagnosis of mania or bipolar disorder during that period.

Results showed an incidence rate of 10.9 per 1,000 person-years of mania or bipolar disorder across the entire study population. The lowest incidence, 8.3 per 1,000 person-years, was in the 56-65 years age cohort, while those in the 26-35 years age cohort had the highest incidence rate – 12.3 per 1,000 person-years (P = .004).

Subjects with prior antidepressant use saw significant increases in incidence rates of mania or bipolar disorder, depending on which antidepressant they were taking. Those on tricyclics (4.7% of subjects with previous antidepressant treatment) had a 13.1 per 1,000 person-years incidence rate, while those taking trazodone (0.8%) had a 19.1 per 1,000 person-years incidence rate (P = .09 and P = .03, respectively). The most commonly used antidepressants were selective serotonin reuptake inhibitors (35.5%), which yielded an incidence rate of 13.2 per 1,000 person-years.

“The association of antidepressant therapy with mania demonstrated in the present and previous studies highlights the importance of considering whether an individual who presents with depression could be at risk of future episodes of mania,” the authors concluded. They concluded that the findings reinforce the “ongoing need to develop better ways to predict future risk of mania in people with no prior history of bipolar disorder who present with an episode of depression.”

The study was supported by the U.K. Medical Research Council Clinical Research Training Fellowship. Neither Dr. Patel nor his associates reported relevant financial disclosures.

[email protected]

One of the most apparent and difficult-to-treat aspects of the aging eye is the descent of the eyebrow. The change in the orbital bone structure as well as fat loss and fat redistribution along the upper and lower eyelids and loss of skin elasticity contribute to the skeletonization of the periorbital area and a “drooping” of the eyebrow. Patients either have loss of volume across the entire brow, or primarily across the lateral and central brow creating what is known as an “a-frame” deformity.

Nonsurgical techniques that help lift the brow include a combination of relaxation of the orbicularis oculi muscle with neurotoxins, in addition to the injection of hyaluronic acid fillers along the brow margin and upper third of the face.

Small amounts of hyaluronic acid fillers injected with a 22- to 25-gauge cannula both above and below the eyebrow along the orbital rim provide an instantaneous lifting effect with long-lasting results. Hyaluronic acid and poly-L-lactic acid in dilute concentrations can also be injected with a cannula in the forehead, which creates a repletion of the volume in the upper face that is often lost with aging to create a lift of the eyebrows. Temple hollows can also be filled with calcium hydroxylapatite, poly-L-lactic acid and less often with hyaluronic acid to revolumize and create a lift of the lateral brow. Care should be taken as fillers used in these areas are off-label and need to be done by trained, expert injectors. The periorbital area is a danger zone with many vessels and nerves, and proper injection technique is crucial to avoid arterial blockage, nerve damage, and long-term complications.

Nonablative skin tightening with radiofrequency energy or ultrasound can be used for achieving a brow-lift. Although these techniques do provide collagen remodeling, multiple procedures are often necessary, and results are not always substantial. In a study of 36 patients undergoing ultrasound tightening of the face and neck, 86% showed a clinically significant brow-lift 90 days after treatment. The average brow elevation in this study was 1.7 mm.

In practice, however, patients are often more satisfied with the brow elevation they achieve with neurotoxins and fillers. Injectables provide a faster onset of results, fewer treatments, and minimal discomfort. Combination treatments provide the best overall results and although injectables in the periorbital area are technically difficult, patients are often very satisfied and return for repeat treatments.

References Aesthet Surg J. 2009;May-Jun;29(3):174-9.

J Am Acad Dermatol. 2010;Feb;62(2):262-9.

Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub.

One of the most apparent and difficult-to-treat aspects of the aging eye is the descent of the eyebrow. The change in the orbital bone structure as well as fat loss and fat redistribution along the upper and lower eyelids and loss of skin elasticity contribute to the skeletonization of the periorbital area and a “drooping” of the eyebrow. Patients either have loss of volume across the entire brow, or primarily across the lateral and central brow creating what is known as an “a-frame” deformity.

Nonsurgical techniques that help lift the brow include a combination of relaxation of the orbicularis oculi muscle with neurotoxins, in addition to the injection of hyaluronic acid fillers along the brow margin and upper third of the face.

Small amounts of hyaluronic acid fillers injected with a 22- to 25-gauge cannula both above and below the eyebrow along the orbital rim provide an instantaneous lifting effect with long-lasting results. Hyaluronic acid and poly-L-lactic acid in dilute concentrations can also be injected with a cannula in the forehead, which creates a repletion of the volume in the upper face that is often lost with aging to create a lift of the eyebrows. Temple hollows can also be filled with calcium hydroxylapatite, poly-L-lactic acid and less often with hyaluronic acid to revolumize and create a lift of the lateral brow. Care should be taken as fillers used in these areas are off-label and need to be done by trained, expert injectors. The periorbital area is a danger zone with many vessels and nerves, and proper injection technique is crucial to avoid arterial blockage, nerve damage, and long-term complications.

Nonablative skin tightening with radiofrequency energy or ultrasound can be used for achieving a brow-lift. Although these techniques do provide collagen remodeling, multiple procedures are often necessary, and results are not always substantial. In a study of 36 patients undergoing ultrasound tightening of the face and neck, 86% showed a clinically significant brow-lift 90 days after treatment. The average brow elevation in this study was 1.7 mm.

In practice, however, patients are often more satisfied with the brow elevation they achieve with neurotoxins and fillers. Injectables provide a faster onset of results, fewer treatments, and minimal discomfort. Combination treatments provide the best overall results and although injectables in the periorbital area are technically difficult, patients are often very satisfied and return for repeat treatments.

References Aesthet Surg J. 2009;May-Jun;29(3):174-9.

J Am Acad Dermatol. 2010;Feb;62(2):262-9.

Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub.

One of the most apparent and difficult-to-treat aspects of the aging eye is the descent of the eyebrow. The change in the orbital bone structure as well as fat loss and fat redistribution along the upper and lower eyelids and loss of skin elasticity contribute to the skeletonization of the periorbital area and a “drooping” of the eyebrow. Patients either have loss of volume across the entire brow, or primarily across the lateral and central brow creating what is known as an “a-frame” deformity.

Nonsurgical techniques that help lift the brow include a combination of relaxation of the orbicularis oculi muscle with neurotoxins, in addition to the injection of hyaluronic acid fillers along the brow margin and upper third of the face.

Small amounts of hyaluronic acid fillers injected with a 22- to 25-gauge cannula both above and below the eyebrow along the orbital rim provide an instantaneous lifting effect with long-lasting results. Hyaluronic acid and poly-L-lactic acid in dilute concentrations can also be injected with a cannula in the forehead, which creates a repletion of the volume in the upper face that is often lost with aging to create a lift of the eyebrows. Temple hollows can also be filled with calcium hydroxylapatite, poly-L-lactic acid and less often with hyaluronic acid to revolumize and create a lift of the lateral brow. Care should be taken as fillers used in these areas are off-label and need to be done by trained, expert injectors. The periorbital area is a danger zone with many vessels and nerves, and proper injection technique is crucial to avoid arterial blockage, nerve damage, and long-term complications.

Nonablative skin tightening with radiofrequency energy or ultrasound can be used for achieving a brow-lift. Although these techniques do provide collagen remodeling, multiple procedures are often necessary, and results are not always substantial. In a study of 36 patients undergoing ultrasound tightening of the face and neck, 86% showed a clinically significant brow-lift 90 days after treatment. The average brow elevation in this study was 1.7 mm.

In practice, however, patients are often more satisfied with the brow elevation they achieve with neurotoxins and fillers. Injectables provide a faster onset of results, fewer treatments, and minimal discomfort. Combination treatments provide the best overall results and although injectables in the periorbital area are technically difficult, patients are often very satisfied and return for repeat treatments.

References Aesthet Surg J. 2009;May-Jun;29(3):174-9.

J Am Acad Dermatol. 2010;Feb;62(2):262-9.

Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub.

SAN DIEGO – Among incident hemodialysis patients, high-density lipoprotein cholesterol levels remained stable over time in men but mildly decreased over time in women, regardless of age.

In addition, larger deviations in HDL cholesterol in the first 6 months of incident hemodialysis were associated with a higher risk of 5-year all-cause mortality.

Those are key findings from a large analysis of patients who received hemodialysis care over a 4-year period, which was presented at the meeting sponsored by the American Society of Nephrology.

“Elevated high-density lipoprotein cholesterol levels, although protective in the general population, can be associated with higher mortality in hemodialysis patients,” Dr. Kamyar Kalantar-Zadeh and his colleagues wrote in an abstract of the study. “Association of HDL change over time with mortality has yet to be examined.”

Dr. Kalantar-Zadeh of the division of nephrology and hypertension at the University of California, Irvine, and his associates examined changes in HDL cholesterol levels over time in 24,400 incident hemodialysis patients who received care from facilities affiliated with DaVita HealthCare Partners between 2007 and 2011.

They examined the association of delta HDL (HDL cholesterol change between the first and second 91-day interval from dialysis start) and HDL cholesterol trajectory with all-cause mortality, using mixed effect and Cox regression models and adjusted for demographics, comorbidities, and baseline HDL cholesterol. Delta HDL was treated both as a continuous variable using restricted cubic splines and in five categories ranging from less than –6 mg/dL to 6 mg/dL or greater.

The mean age of patients was 65 years, 44% were female, 31% were black, and 66% had diabetes.

Mean baseline HDL cholesterol was 40.5 mg/dL, with an HDL cholesterol change of 1.7 mg/dL. The researchers found that while male patients had no significant change in HDL cholesterol over time, females had a significant decrease in HDL cholesterol (a mean of –0.6mg/dL per year). At the same time, a 6 mg/dL or greater increase or decrease in delta HDL was associated with a 7% and 37% increase in all-cause mortality, respectively, compared with the reference group. Delta HDL mortality associations did not differ across gender.

“Patients who have a greater than 6 mg/dL change in HDL between the first and second patient [tests] have a higher risk of 5-year all-cause mortality,” the researchers concluded. “Change in HDL exhibits a reverse J-shaped association with mortality in hemodialysis patients. Further studies are needed to examine the underlying causes of these HDL changes and pathophysiology leading to higher risk of all-cause mortality.”

The study was supported by funding from the National Institute of Diabetes and Digestive and Kidney Diseases. The researchers reported having no financial disclosures.

[email protected]

SAN DIEGO – Among incident hemodialysis patients, high-density lipoprotein cholesterol levels remained stable over time in men but mildly decreased over time in women, regardless of age.

In addition, larger deviations in HDL cholesterol in the first 6 months of incident hemodialysis were associated with a higher risk of 5-year all-cause mortality.

Those are key findings from a large analysis of patients who received hemodialysis care over a 4-year period, which was presented at the meeting sponsored by the American Society of Nephrology.

“Elevated high-density lipoprotein cholesterol levels, although protective in the general population, can be associated with higher mortality in hemodialysis patients,” Dr. Kamyar Kalantar-Zadeh and his colleagues wrote in an abstract of the study. “Association of HDL change over time with mortality has yet to be examined.”

Dr. Kalantar-Zadeh of the division of nephrology and hypertension at the University of California, Irvine, and his associates examined changes in HDL cholesterol levels over time in 24,400 incident hemodialysis patients who received care from facilities affiliated with DaVita HealthCare Partners between 2007 and 2011.

They examined the association of delta HDL (HDL cholesterol change between the first and second 91-day interval from dialysis start) and HDL cholesterol trajectory with all-cause mortality, using mixed effect and Cox regression models and adjusted for demographics, comorbidities, and baseline HDL cholesterol. Delta HDL was treated both as a continuous variable using restricted cubic splines and in five categories ranging from less than –6 mg/dL to 6 mg/dL or greater.

The mean age of patients was 65 years, 44% were female, 31% were black, and 66% had diabetes.

Mean baseline HDL cholesterol was 40.5 mg/dL, with an HDL cholesterol change of 1.7 mg/dL. The researchers found that while male patients had no significant change in HDL cholesterol over time, females had a significant decrease in HDL cholesterol (a mean of –0.6mg/dL per year). At the same time, a 6 mg/dL or greater increase or decrease in delta HDL was associated with a 7% and 37% increase in all-cause mortality, respectively, compared with the reference group. Delta HDL mortality associations did not differ across gender.

“Patients who have a greater than 6 mg/dL change in HDL between the first and second patient [tests] have a higher risk of 5-year all-cause mortality,” the researchers concluded. “Change in HDL exhibits a reverse J-shaped association with mortality in hemodialysis patients. Further studies are needed to examine the underlying causes of these HDL changes and pathophysiology leading to higher risk of all-cause mortality.”

The study was supported by funding from the National Institute of Diabetes and Digestive and Kidney Diseases. The researchers reported having no financial disclosures.

[email protected]

SAN DIEGO – Among incident hemodialysis patients, high-density lipoprotein cholesterol levels remained stable over time in men but mildly decreased over time in women, regardless of age.

In addition, larger deviations in HDL cholesterol in the first 6 months of incident hemodialysis were associated with a higher risk of 5-year all-cause mortality.

Those are key findings from a large analysis of patients who received hemodialysis care over a 4-year period, which was presented at the meeting sponsored by the American Society of Nephrology.

“Elevated high-density lipoprotein cholesterol levels, although protective in the general population, can be associated with higher mortality in hemodialysis patients,” Dr. Kamyar Kalantar-Zadeh and his colleagues wrote in an abstract of the study. “Association of HDL change over time with mortality has yet to be examined.”

Dr. Kalantar-Zadeh of the division of nephrology and hypertension at the University of California, Irvine, and his associates examined changes in HDL cholesterol levels over time in 24,400 incident hemodialysis patients who received care from facilities affiliated with DaVita HealthCare Partners between 2007 and 2011.

They examined the association of delta HDL (HDL cholesterol change between the first and second 91-day interval from dialysis start) and HDL cholesterol trajectory with all-cause mortality, using mixed effect and Cox regression models and adjusted for demographics, comorbidities, and baseline HDL cholesterol. Delta HDL was treated both as a continuous variable using restricted cubic splines and in five categories ranging from less than –6 mg/dL to 6 mg/dL or greater.

The mean age of patients was 65 years, 44% were female, 31% were black, and 66% had diabetes.

Mean baseline HDL cholesterol was 40.5 mg/dL, with an HDL cholesterol change of 1.7 mg/dL. The researchers found that while male patients had no significant change in HDL cholesterol over time, females had a significant decrease in HDL cholesterol (a mean of –0.6mg/dL per year). At the same time, a 6 mg/dL or greater increase or decrease in delta HDL was associated with a 7% and 37% increase in all-cause mortality, respectively, compared with the reference group. Delta HDL mortality associations did not differ across gender.

“Patients who have a greater than 6 mg/dL change in HDL between the first and second patient [tests] have a higher risk of 5-year all-cause mortality,” the researchers concluded. “Change in HDL exhibits a reverse J-shaped association with mortality in hemodialysis patients. Further studies are needed to examine the underlying causes of these HDL changes and pathophysiology leading to higher risk of all-cause mortality.”

The study was supported by funding from the National Institute of Diabetes and Digestive and Kidney Diseases. The researchers reported having no financial disclosures.

[email protected]

Concerns with delayed right ventricle dysfunction have offset the early survival advantages after Norwood procedure with right ventricle to pulmonary artery conduit (NW-RVPA) over the Norwood with Blalock-Taussig shunt (NW-BT) in newborns with left ventricular outflow tract obstruction, but a recent report provides evidence that RV function between the two procedures is comparable for up to six years.

Reporting in the January issue of the Journal of Thoracic and Cardiovascular Surgery (J Thorac Cardiovasc Surg. 2015 Dec;150:1440–52), investigators for the Congenital Heart Surgeons’ Society (CHSS) trial found that NW-RVPA has better overall six-year survival and superior right ventricle function in the short term after surgery than NW-BT. The study involved 454 newborns with critical left ventricular outflow tract obstruction (LVOTO) in the CHSS database who had Norwood stage-1 from 2005 to 2014. Propensity matching paired 169 NW-RVPA patients with the same number of NW-BT patients for comparison. CHSS along with the Hospital for Sick Children in Toronto provided funding for the study.

“For neonates with critical LVOTO and similar baseline characteristics undergoing a Norwood stage-1 operation, the six-year overall survival and transplant-free survival were significantly better after NW-RVPA vs. NW-BT,” said Dr. Travis J. Wilder and his colleagues from the Hospital for Sick Children in Toronto.

Key questions the study sought to answer involved the clinical implications of the small variations in RV function between the two procedures, as well as the association between Norwood procedures and tricuspid valve regurgitation (TR) and overall survival.

Overall six-year survival was 70% for the NW-RVPA group vs. 55% for the NW-BT group. Right ventricle dysfunction rates three months after the procedure were lower for the NW-RVPA group, 6% vs. 16%, but rates of late RV dysfunction were less than 5% for both groups. Likewise, rates of moderate or greater TR at two years were lower in the NW-RVPA group: 11% vs. 16%.

Rates of Fontan operation after six years were higher among the NW-RVPA group (54% vs. 49%), as were transplantation rates (6% vs. 2%). Overall, 2% converted to a biventricular repair, but only after NW-RVPA; and seven patients who had NW-RVPA underwent a tricuspid valve repair, compared with four in the NW-BT group.

“For all survivors not undergoing transplantation or biventricular repair, the prevalence of late moderate or greater RV dysfunction and TR were similar between NW-BT and NW-RVPA at six years, without evidence of increased RV dysfunction for patients who underwent NW-RVPA,” Dr. Wilder and his colleagues said.

Consistent with previous studies, the CHSS study showed an early risk of death after a Norwood stage-1 operation, which may be due to a greater prevalence of significant RV dysfunction as the operation transitions from stage 1 to stage 2, Dr. Wilder and his coauthors said. “Although causation between these two time-related events cannot directly be made, it suggests that poor RV function contributes to early hazard for death,” they said.

The authors acknowledge a number of limitations with their study: the variation in the quality of echocardiogram reports from the multiple institutions involved, the inability of propensity matching to account for unmeasured factors and the influence of center and surgeon volume among participating sites. They also said that the ventriculotomy the NW-RVPA involves can lead to late aneurysm, arrhythmias, and ventricular failure. The adverse effects of ventriculotomy on long-term RV function “may not become apparent for years,” Dr. Wilder and his coauthors said.

Dr. Wilder presented a report of the original results at the 2015 American Association for Thoracic Surgery Annual meeting.

The authors had no relationships to disclose.

Concerns with delayed right ventricle dysfunction have offset the early survival advantages after Norwood procedure with right ventricle to pulmonary artery conduit (NW-RVPA) over the Norwood with Blalock-Taussig shunt (NW-BT) in newborns with left ventricular outflow tract obstruction, but a recent report provides evidence that RV function between the two procedures is comparable for up to six years.

Reporting in the January issue of the Journal of Thoracic and Cardiovascular Surgery (J Thorac Cardiovasc Surg. 2015 Dec;150:1440–52), investigators for the Congenital Heart Surgeons’ Society (CHSS) trial found that NW-RVPA has better overall six-year survival and superior right ventricle function in the short term after surgery than NW-BT. The study involved 454 newborns with critical left ventricular outflow tract obstruction (LVOTO) in the CHSS database who had Norwood stage-1 from 2005 to 2014. Propensity matching paired 169 NW-RVPA patients with the same number of NW-BT patients for comparison. CHSS along with the Hospital for Sick Children in Toronto provided funding for the study.

“For neonates with critical LVOTO and similar baseline characteristics undergoing a Norwood stage-1 operation, the six-year overall survival and transplant-free survival were significantly better after NW-RVPA vs. NW-BT,” said Dr. Travis J. Wilder and his colleagues from the Hospital for Sick Children in Toronto.

Key questions the study sought to answer involved the clinical implications of the small variations in RV function between the two procedures, as well as the association between Norwood procedures and tricuspid valve regurgitation (TR) and overall survival.

Overall six-year survival was 70% for the NW-RVPA group vs. 55% for the NW-BT group. Right ventricle dysfunction rates three months after the procedure were lower for the NW-RVPA group, 6% vs. 16%, but rates of late RV dysfunction were less than 5% for both groups. Likewise, rates of moderate or greater TR at two years were lower in the NW-RVPA group: 11% vs. 16%.

Rates of Fontan operation after six years were higher among the NW-RVPA group (54% vs. 49%), as were transplantation rates (6% vs. 2%). Overall, 2% converted to a biventricular repair, but only after NW-RVPA; and seven patients who had NW-RVPA underwent a tricuspid valve repair, compared with four in the NW-BT group.

“For all survivors not undergoing transplantation or biventricular repair, the prevalence of late moderate or greater RV dysfunction and TR were similar between NW-BT and NW-RVPA at six years, without evidence of increased RV dysfunction for patients who underwent NW-RVPA,” Dr. Wilder and his colleagues said.

Consistent with previous studies, the CHSS study showed an early risk of death after a Norwood stage-1 operation, which may be due to a greater prevalence of significant RV dysfunction as the operation transitions from stage 1 to stage 2, Dr. Wilder and his coauthors said. “Although causation between these two time-related events cannot directly be made, it suggests that poor RV function contributes to early hazard for death,” they said.

The authors acknowledge a number of limitations with their study: the variation in the quality of echocardiogram reports from the multiple institutions involved, the inability of propensity matching to account for unmeasured factors and the influence of center and surgeon volume among participating sites. They also said that the ventriculotomy the NW-RVPA involves can lead to late aneurysm, arrhythmias, and ventricular failure. The adverse effects of ventriculotomy on long-term RV function “may not become apparent for years,” Dr. Wilder and his coauthors said.

Dr. Wilder presented a report of the original results at the 2015 American Association for Thoracic Surgery Annual meeting.

The authors had no relationships to disclose.

Concerns with delayed right ventricle dysfunction have offset the early survival advantages after Norwood procedure with right ventricle to pulmonary artery conduit (NW-RVPA) over the Norwood with Blalock-Taussig shunt (NW-BT) in newborns with left ventricular outflow tract obstruction, but a recent report provides evidence that RV function between the two procedures is comparable for up to six years.

Reporting in the January issue of the Journal of Thoracic and Cardiovascular Surgery (J Thorac Cardiovasc Surg. 2015 Dec;150:1440–52), investigators for the Congenital Heart Surgeons’ Society (CHSS) trial found that NW-RVPA has better overall six-year survival and superior right ventricle function in the short term after surgery than NW-BT. The study involved 454 newborns with critical left ventricular outflow tract obstruction (LVOTO) in the CHSS database who had Norwood stage-1 from 2005 to 2014. Propensity matching paired 169 NW-RVPA patients with the same number of NW-BT patients for comparison. CHSS along with the Hospital for Sick Children in Toronto provided funding for the study.

“For neonates with critical LVOTO and similar baseline characteristics undergoing a Norwood stage-1 operation, the six-year overall survival and transplant-free survival were significantly better after NW-RVPA vs. NW-BT,” said Dr. Travis J. Wilder and his colleagues from the Hospital for Sick Children in Toronto.

Key questions the study sought to answer involved the clinical implications of the small variations in RV function between the two procedures, as well as the association between Norwood procedures and tricuspid valve regurgitation (TR) and overall survival.

Overall six-year survival was 70% for the NW-RVPA group vs. 55% for the NW-BT group. Right ventricle dysfunction rates three months after the procedure were lower for the NW-RVPA group, 6% vs. 16%, but rates of late RV dysfunction were less than 5% for both groups. Likewise, rates of moderate or greater TR at two years were lower in the NW-RVPA group: 11% vs. 16%.

Rates of Fontan operation after six years were higher among the NW-RVPA group (54% vs. 49%), as were transplantation rates (6% vs. 2%). Overall, 2% converted to a biventricular repair, but only after NW-RVPA; and seven patients who had NW-RVPA underwent a tricuspid valve repair, compared with four in the NW-BT group.

“For all survivors not undergoing transplantation or biventricular repair, the prevalence of late moderate or greater RV dysfunction and TR were similar between NW-BT and NW-RVPA at six years, without evidence of increased RV dysfunction for patients who underwent NW-RVPA,” Dr. Wilder and his colleagues said.

Consistent with previous studies, the CHSS study showed an early risk of death after a Norwood stage-1 operation, which may be due to a greater prevalence of significant RV dysfunction as the operation transitions from stage 1 to stage 2, Dr. Wilder and his coauthors said. “Although causation between these two time-related events cannot directly be made, it suggests that poor RV function contributes to early hazard for death,” they said.

The authors acknowledge a number of limitations with their study: the variation in the quality of echocardiogram reports from the multiple institutions involved, the inability of propensity matching to account for unmeasured factors and the influence of center and surgeon volume among participating sites. They also said that the ventriculotomy the NW-RVPA involves can lead to late aneurysm, arrhythmias, and ventricular failure. The adverse effects of ventriculotomy on long-term RV function “may not become apparent for years,” Dr. Wilder and his coauthors said.

Dr. Wilder presented a report of the original results at the 2015 American Association for Thoracic Surgery Annual meeting.

The authors had no relationships to disclose.

SAN DIEGO – Among patients with chronic kidney disease, LDL cholesterol level was positively associated with risk of atherosclerotic vascular events, regardless of baseline inflammation, according to a large, randomized study.

In addition, lowering LDL cholesterol with ezetimibe/simvastatin was similarly effective in the presence or absence of inflammation.

“There has been substantial interest in the relationship between LDL cholesterol and outcomes in the general population, and in particular among people with kidney disease,” study author Dr. Richard Haynes of the Nuffield Department of Population Health at the University of Oxford (England) said in an interview in advance of the meeting.

“Previous studies have found a paradoxical increased risk of death at low cholesterol levels, which may be due to another disease process – such as inflammation – both lowering cholesterol and increasing the risk of death, thereby creating a false association,” he explained.

Dr. Haynes and his associates set out to determine the relevance of LDL cholesterol and C-reactive protein (CRP) to cardiovascular risk among 9,270 patients with chronic kidney disease who were enrolled in the Study of Heart and Renal Protection (SHARP), in which they received either ezetimibe/simvastatin or placebo.

The researchers used Cox regression to analyze the hazard ratio for all atherosclerotic vascular events over a period of 4.9 years. The effect of ezetimibe/simvastatin on major atherosclerotic events was estimated in the presence and absence of inflammation, which was defined as a CRP of 3 mg/L. The mean age of SHARP participants was 62 years, and 63% were men.

Dr. Ben Storey, a colleague of Dr. Haynes at Oxford, reported the study results at the meeting sponsored by the American Society of Nephrology.

Among all patients, usual LDL was positively associated with the risk of atherosclerotic vascular events (hazard ratio, 1.34). Compared with patients who had low CRP, those with high CRP were at higher risk, but the relationship between LDL-C and atherosclerotic vascular event risk was similar in both groups (HR, 1.32 and 1.41, respectively).

Ezetimibe/simvastatin was similarly effective at reducing major atherosclerotic events in patients with low and high CRP (risk ratio, 0.84 and 0.83, respectively). Sensitivity analyses yielded similar results.

“The observational data from SHARP show that LDL cholesterol is positively associated with the risk of atherosclerotic vascular events, irrespective of baseline inflammation,” Dr. Storey concluded. “The randomized evidence showed that lowering LDL cholesterol was similarly effective in the presence or absence of inflammation, but CRP is associated with vascular risk in [chronic kidney disease].”

The findings’ clinical implications are that inflammation, “while it is relevant to patients’ outcomes, does not modify the beneficial effects of lowering LDL cholesterol,” according to Dr. Haynes, “So, clinicians should not be put off from prescribing statin-based, cholesterol-lowering therapy by the presence – or absence – of inflammation.”

Merck funded SHARP, but the University of Oxford conducted and analyzed the study independently. The Australian National Health and Medical Research Council, the British Heart Foundation, Cancer Research UK, and the UK Medical Research Council provided additional support.

[email protected]

SAN DIEGO – Among patients with chronic kidney disease, LDL cholesterol level was positively associated with risk of atherosclerotic vascular events, regardless of baseline inflammation, according to a large, randomized study.

In addition, lowering LDL cholesterol with ezetimibe/simvastatin was similarly effective in the presence or absence of inflammation.

“There has been substantial interest in the relationship between LDL cholesterol and outcomes in the general population, and in particular among people with kidney disease,” study author Dr. Richard Haynes of the Nuffield Department of Population Health at the University of Oxford (England) said in an interview in advance of the meeting.

“Previous studies have found a paradoxical increased risk of death at low cholesterol levels, which may be due to another disease process – such as inflammation – both lowering cholesterol and increasing the risk of death, thereby creating a false association,” he explained.

Dr. Haynes and his associates set out to determine the relevance of LDL cholesterol and C-reactive protein (CRP) to cardiovascular risk among 9,270 patients with chronic kidney disease who were enrolled in the Study of Heart and Renal Protection (SHARP), in which they received either ezetimibe/simvastatin or placebo.

The researchers used Cox regression to analyze the hazard ratio for all atherosclerotic vascular events over a period of 4.9 years. The effect of ezetimibe/simvastatin on major atherosclerotic events was estimated in the presence and absence of inflammation, which was defined as a CRP of 3 mg/L. The mean age of SHARP participants was 62 years, and 63% were men.

Dr. Ben Storey, a colleague of Dr. Haynes at Oxford, reported the study results at the meeting sponsored by the American Society of Nephrology.

Among all patients, usual LDL was positively associated with the risk of atherosclerotic vascular events (hazard ratio, 1.34). Compared with patients who had low CRP, those with high CRP were at higher risk, but the relationship between LDL-C and atherosclerotic vascular event risk was similar in both groups (HR, 1.32 and 1.41, respectively).

Ezetimibe/simvastatin was similarly effective at reducing major atherosclerotic events in patients with low and high CRP (risk ratio, 0.84 and 0.83, respectively). Sensitivity analyses yielded similar results.

“The observational data from SHARP show that LDL cholesterol is positively associated with the risk of atherosclerotic vascular events, irrespective of baseline inflammation,” Dr. Storey concluded. “The randomized evidence showed that lowering LDL cholesterol was similarly effective in the presence or absence of inflammation, but CRP is associated with vascular risk in [chronic kidney disease].”

The findings’ clinical implications are that inflammation, “while it is relevant to patients’ outcomes, does not modify the beneficial effects of lowering LDL cholesterol,” according to Dr. Haynes, “So, clinicians should not be put off from prescribing statin-based, cholesterol-lowering therapy by the presence – or absence – of inflammation.”

Merck funded SHARP, but the University of Oxford conducted and analyzed the study independently. The Australian National Health and Medical Research Council, the British Heart Foundation, Cancer Research UK, and the UK Medical Research Council provided additional support.

[email protected]

SAN DIEGO – Among patients with chronic kidney disease, LDL cholesterol level was positively associated with risk of atherosclerotic vascular events, regardless of baseline inflammation, according to a large, randomized study.

In addition, lowering LDL cholesterol with ezetimibe/simvastatin was similarly effective in the presence or absence of inflammation.

“There has been substantial interest in the relationship between LDL cholesterol and outcomes in the general population, and in particular among people with kidney disease,” study author Dr. Richard Haynes of the Nuffield Department of Population Health at the University of Oxford (England) said in an interview in advance of the meeting.

“Previous studies have found a paradoxical increased risk of death at low cholesterol levels, which may be due to another disease process – such as inflammation – both lowering cholesterol and increasing the risk of death, thereby creating a false association,” he explained.

Dr. Haynes and his associates set out to determine the relevance of LDL cholesterol and C-reactive protein (CRP) to cardiovascular risk among 9,270 patients with chronic kidney disease who were enrolled in the Study of Heart and Renal Protection (SHARP), in which they received either ezetimibe/simvastatin or placebo.

The researchers used Cox regression to analyze the hazard ratio for all atherosclerotic vascular events over a period of 4.9 years. The effect of ezetimibe/simvastatin on major atherosclerotic events was estimated in the presence and absence of inflammation, which was defined as a CRP of 3 mg/L. The mean age of SHARP participants was 62 years, and 63% were men.

Dr. Ben Storey, a colleague of Dr. Haynes at Oxford, reported the study results at the meeting sponsored by the American Society of Nephrology.

Among all patients, usual LDL was positively associated with the risk of atherosclerotic vascular events (hazard ratio, 1.34). Compared with patients who had low CRP, those with high CRP were at higher risk, but the relationship between LDL-C and atherosclerotic vascular event risk was similar in both groups (HR, 1.32 and 1.41, respectively).

Ezetimibe/simvastatin was similarly effective at reducing major atherosclerotic events in patients with low and high CRP (risk ratio, 0.84 and 0.83, respectively). Sensitivity analyses yielded similar results.

“The observational data from SHARP show that LDL cholesterol is positively associated with the risk of atherosclerotic vascular events, irrespective of baseline inflammation,” Dr. Storey concluded. “The randomized evidence showed that lowering LDL cholesterol was similarly effective in the presence or absence of inflammation, but CRP is associated with vascular risk in [chronic kidney disease].”

The findings’ clinical implications are that inflammation, “while it is relevant to patients’ outcomes, does not modify the beneficial effects of lowering LDL cholesterol,” according to Dr. Haynes, “So, clinicians should not be put off from prescribing statin-based, cholesterol-lowering therapy by the presence – or absence – of inflammation.”

Merck funded SHARP, but the University of Oxford conducted and analyzed the study independently. The Australian National Health and Medical Research Council, the British Heart Foundation, Cancer Research UK, and the UK Medical Research Council provided additional support.

[email protected]

ORLANDO – Patients with acute myeloid leukemia (AML) initially treated at an academic center lived significantly longer than those treated at nonacademic centers, a database analysis shows.

Median overall survival increased from 7 months at a nonacademic center to 12.6 months at an academic center (P less than .001).

One-year overall survival rates were also significantly better at 51% vs. 39% (P less than .001).

Patrice Wendling/Frontline Medical News

The difference remained significant even after controlling for important confounders including age, comorbidity burden, receipt of chemotherapy, transplant, and delay between diagnosis and treatment, Mr. Smith Giri reported at the annual meeting of the American Society of Hematology.

“From a policy perspective, it may be useful to know whether these results are due to higher volume of cases, more advanced technology, expanded role of specialists, or greater, round-the-clock availability of resident physicians,” said Mr. Giri of the University of Tennessee Health Science Center in Memphis.

Prior studies in cancer have suggested better overall survival among breast cancer patients treated at academic centers, but this is the first study looking at outcomes in AML, the most common acute leukemia in adults.

Using the National Cancer Database Participant User File, the investigators identified 7,823 patients with AML who received their initial therapy at the reporting facility from 1998 to 2011. The database collects information from more than 1,500 Commission on Cancer (CoC)–accredited facilities. Of the 7,823 patients, 4,681 (60%) were treated at an AC (academic/research program) and 3,142 at a non-AC (community cancer program/comprehensive community cancer program).

Patients treated at an AC were significantly younger than those treated at a non-AC (median 62 years vs. 67 years), tended to be of nonwhite race, less educated, have a lower income, and more comorbidities.

Receipt of chemotherapy (97.4% vs. 94.5%) and transplant (9% vs. 2.4%) were significantly higher at an AC than a non-AC (both P less than .001).

Kaplan Meier survival curves suggested disparate survival curves between the two groups, mainly within the first 5 years of follow-up (P less than .001), Mr. Giri said.

In multivariate model analysis, the non-AC group had significantly worse risk adjusted 30-day mortality than the AC group (odds ratio, 1.52; 95% confidence interval 1.33-1.74; P less than .001) and worse overall survival (hazard ratio, 1.13; 95% CI 1.07-1.19; P less than .001).

The study (Ab. 533) findings should be interpreted with caution because of its limitations, including the lack of information on AML risk type in the database, the fact that administrative datasets are prone to coding errors, and because the analysis did not adjust for hospital volume, which has been shown to affect survival, he said. Also, because there are more than 3,500 non–Coc approved hospitals, the sample may not be representative of overall U.S. hospitals.

During a discussion of the results, Mr. Giri acknowledged that patients treated at academic centers may have greater access to clinical trials and experimental agents. Future analyses should also distinguish patients with a diagnosis of acute promyelocytic leukemia, a distinct subset of AML.

[email protected]

ORLANDO – Patients with acute myeloid leukemia (AML) initially treated at an academic center lived significantly longer than those treated at nonacademic centers, a database analysis shows.

Median overall survival increased from 7 months at a nonacademic center to 12.6 months at an academic center (P less than .001).

One-year overall survival rates were also significantly better at 51% vs. 39% (P less than .001).

Patrice Wendling/Frontline Medical News

The difference remained significant even after controlling for important confounders including age, comorbidity burden, receipt of chemotherapy, transplant, and delay between diagnosis and treatment, Mr. Smith Giri reported at the annual meeting of the American Society of Hematology.

“From a policy perspective, it may be useful to know whether these results are due to higher volume of cases, more advanced technology, expanded role of specialists, or greater, round-the-clock availability of resident physicians,” said Mr. Giri of the University of Tennessee Health Science Center in Memphis.

Prior studies in cancer have suggested better overall survival among breast cancer patients treated at academic centers, but this is the first study looking at outcomes in AML, the most common acute leukemia in adults.

Using the National Cancer Database Participant User File, the investigators identified 7,823 patients with AML who received their initial therapy at the reporting facility from 1998 to 2011. The database collects information from more than 1,500 Commission on Cancer (CoC)–accredited facilities. Of the 7,823 patients, 4,681 (60%) were treated at an AC (academic/research program) and 3,142 at a non-AC (community cancer program/comprehensive community cancer program).

Patients treated at an AC were significantly younger than those treated at a non-AC (median 62 years vs. 67 years), tended to be of nonwhite race, less educated, have a lower income, and more comorbidities.

Receipt of chemotherapy (97.4% vs. 94.5%) and transplant (9% vs. 2.4%) were significantly higher at an AC than a non-AC (both P less than .001).

Kaplan Meier survival curves suggested disparate survival curves between the two groups, mainly within the first 5 years of follow-up (P less than .001), Mr. Giri said.

In multivariate model analysis, the non-AC group had significantly worse risk adjusted 30-day mortality than the AC group (odds ratio, 1.52; 95% confidence interval 1.33-1.74; P less than .001) and worse overall survival (hazard ratio, 1.13; 95% CI 1.07-1.19; P less than .001).

The study (Ab. 533) findings should be interpreted with caution because of its limitations, including the lack of information on AML risk type in the database, the fact that administrative datasets are prone to coding errors, and because the analysis did not adjust for hospital volume, which has been shown to affect survival, he said. Also, because there are more than 3,500 non–Coc approved hospitals, the sample may not be representative of overall U.S. hospitals.

During a discussion of the results, Mr. Giri acknowledged that patients treated at academic centers may have greater access to clinical trials and experimental agents. Future analyses should also distinguish patients with a diagnosis of acute promyelocytic leukemia, a distinct subset of AML.

[email protected]

ORLANDO – Patients with acute myeloid leukemia (AML) initially treated at an academic center lived significantly longer than those treated at nonacademic centers, a database analysis shows.

Median overall survival increased from 7 months at a nonacademic center to 12.6 months at an academic center (P less than .001).

One-year overall survival rates were also significantly better at 51% vs. 39% (P less than .001).

Patrice Wendling/Frontline Medical News

The difference remained significant even after controlling for important confounders including age, comorbidity burden, receipt of chemotherapy, transplant, and delay between diagnosis and treatment, Mr. Smith Giri reported at the annual meeting of the American Society of Hematology.

“From a policy perspective, it may be useful to know whether these results are due to higher volume of cases, more advanced technology, expanded role of specialists, or greater, round-the-clock availability of resident physicians,” said Mr. Giri of the University of Tennessee Health Science Center in Memphis.

Prior studies in cancer have suggested better overall survival among breast cancer patients treated at academic centers, but this is the first study looking at outcomes in AML, the most common acute leukemia in adults.

Using the National Cancer Database Participant User File, the investigators identified 7,823 patients with AML who received their initial therapy at the reporting facility from 1998 to 2011. The database collects information from more than 1,500 Commission on Cancer (CoC)–accredited facilities. Of the 7,823 patients, 4,681 (60%) were treated at an AC (academic/research program) and 3,142 at a non-AC (community cancer program/comprehensive community cancer program).

Patients treated at an AC were significantly younger than those treated at a non-AC (median 62 years vs. 67 years), tended to be of nonwhite race, less educated, have a lower income, and more comorbidities.

Receipt of chemotherapy (97.4% vs. 94.5%) and transplant (9% vs. 2.4%) were significantly higher at an AC than a non-AC (both P less than .001).

Kaplan Meier survival curves suggested disparate survival curves between the two groups, mainly within the first 5 years of follow-up (P less than .001), Mr. Giri said.

In multivariate model analysis, the non-AC group had significantly worse risk adjusted 30-day mortality than the AC group (odds ratio, 1.52; 95% confidence interval 1.33-1.74; P less than .001) and worse overall survival (hazard ratio, 1.13; 95% CI 1.07-1.19; P less than .001).

The study (Ab. 533) findings should be interpreted with caution because of its limitations, including the lack of information on AML risk type in the database, the fact that administrative datasets are prone to coding errors, and because the analysis did not adjust for hospital volume, which has been shown to affect survival, he said. Also, because there are more than 3,500 non–Coc approved hospitals, the sample may not be representative of overall U.S. hospitals.

During a discussion of the results, Mr. Giri acknowledged that patients treated at academic centers may have greater access to clinical trials and experimental agents. Future analyses should also distinguish patients with a diagnosis of acute promyelocytic leukemia, a distinct subset of AML.

[email protected]

Most children and young adult patients with congenital heart disease can and should engage in some form of physical activity and should avoid a sedentary lifestyle, according to a task force scientific statement from the American Heart Association and the American College of Cardiology (AHA/ACC).

This recommendation comes despite the fears of sudden cardiac death (SCD) in young athletes, which formed the initial impetus of the entire series of task force reports.

The recommended level of sports participation for patients with treated or untreated congenital heart defect, however, should consider the training and the competitive aspects of the sport itself and must be individualized to the patient. This means taking into account the patient’s current functional status, history of surgery, and the presence of implanted cardiac devices, according to the report by Dr. George F. Van Hare of Washington University, St. Louis, and his colleagues, which was published online in the Journal of the American College of Cardiology.

© Jody Dingle/Fotolia.com

The report breaks down its specific recommendations based upon the various types of congenital heart defect (CHD). Full details and nuances of the recommendations and their specific levels of evidence for each individual condition and the many variants can be found in the online publication. Below is a brief and selected summary for some of the most common defects and some of those most pertinent to sudden cardiac death in young athletes.

Simple shunting lesions (atrial septal defect, ventricular septal defect, patent ductus arteriosus): Treated and untreated

In addressing the three most common subtypes of CHD – ventricular septal defect (VSD, 34%), atrial septal defect (ASD, 13%), and patent ductus arteriosus (PDA, 10%) – the committee found no data that children with these lesions are related to acknowledged episodes of sudden cardiac death (SCD). This applied whether the defects were closed or remained open. “With rare exceptions, patients with hemodynamically insignificant CHD such as VSD, ASD, and PDA may participate competitively in all sports,” it concluded. These recommendations fall under class I; level of evidence C for almost all of these patients, according to the writing committee.

Congenital coronary anomalies: Treated and untreated

Anomalies of coronary arteries are the second-most commonly identified structural causes of SCD in competitive athletes, accounting for about 17% of such deaths in the United States, according to the report. The vast majority of sudden deaths associated with coronary anomalies occur during or shortly after exercise. Despite being less commonly represented in patients, among athletes who have died suddenly, anomalous origin of the left main or left anterior descending coronary artery from the right sinus of Valsalva is far more prevalent. In addition, SCDs are most strongly associated with the pattern in which the anomalous left coronary artery passes between the aorta and main pulmonary artery. Recommended return to intense athletic activities is only to be permitted at least 3 months after surgery, and with a demonstration of the absence of ischemia on postoperative stress testing, with evidence levels depending on the type of anomaly. Of note, in contrast, the committee indicated that athletes with an anomalous origin of a right coronary artery from the left sinus of Valsalva should simply be evaluated by an exercise stress test, and for those without symptoms or a positive exercise stress test, permission to compete can be considered after adequate counseling (class IIa; level of evidence C).

Pulmonary valve stenosis: Treated and untreated

The committee determined that athletes with mild pulmonary stenosis (PS) and normal right ventricular (RV) function can participate in all competitive sports, although annual reevaluation also is recommended (class I; level of evidence B). In addition, athletes treated by operation or balloon valvuloplasty who have achieved adequate relief of PS (gradient less than 40 mm Hg by Doppler) can participate in all competitive sports (class I; level of evidence B). Other patients should be restricted to low-intensity sports, according to the committee.

Aortic valve stenosis: Treated and untreated

Children and adolescents with aortic stenosis (AS) are differentiated between those with mild, moderate, and severe AS by physical examination, ECG, and Doppler echocardiography. In all cases, regardless of the degree of stenosis, patients with a history of fatigue, light-headedness, dizziness, syncope, chest pain, or pallor on exercise deserve a full evaluation. Annual re-evaluation is required for all patients with AS because the disease can progress. Patients with severe AS are at risk of sudden death, particularly with exercise. The committee determined that athletes with mild AS can participate in all competitive sports (class I; level of evidence B), but that athletes with severe AS should be restricted from all competitive sports, with the possible exception of low-intensity sports (class III; level of evidence B).

Coarctation of the aorta: Treated and untreated

Before a decision is made regarding exercise participation, a detailed evaluation should be conducted, including a physical examination, ECG, chest radiograph, exercise testing, transthoracic echocardiographic evaluation of the aortic valve and aorta, and either magnetic resonance imaging or computed tomography angiography, according to the committee. The determination as to the level of sports participation permitted requires a complex assessment of these various test results and can range from full participation in the case of the least affected to restrictions to low-intensity sports in those more severely affected.

Cyanotic CHD, including tetralogy of Fallot

Full clinical assessment, including laboratory and exercise testing, should be considered before any physical activity because this population is at very high risk of sudden death, according to the committee. Recommendations are complex and depend on the level of repair and its success, but, in general, significant restrictions are recommended for all but the most effectively treated patients.

Transposition of the great arteries after atrial switch (Mustard or Senning operation)

This is a population highly at risk, according to the committee. They appear to have a unique response to exercise with reports that a high proportion of sudden death events occur during exertion. In addition, evidence of exercise-induced arrhythmias on routine clinical testing has not been shown to reliably predict exercise-induced SCD events. Although recommendations vary, including strong restrictions for many, at best the most successful of these patients should only be considered for low- to moderate-intensity competitive sports, according to the committee.

Other conditions assessed and evaluated by the committee included congenitally corrected TGA, TGA after the arterial switch, Fontan procedure, elevated pulmonary vascular resistence in CHD, ventricular dysfunction after CHD surgery, and Ebstein anomaly of the tricuspid valve.

In all cases, complete physical assessment of these patients is recommended, especially due to the often highly individualized nature of the patient’s presentation of these conditions and the variety and variability of interventions that may have been performed. Such differentials make recommendations regarding sports participation a complex calculus, which the committee attempts to provide, listing whatever evidence is available.

The majority of these patients, however, will not be considered for the highest levels of competitive sports participation. Although, in almost all cases, the need for physical activity as a contributor to patient health and well-being is stressed at whatever level of performance is possible.

The report ”Eligibility and disqualification recommendations for competitive athletes with cardiovascular abnormalities: Task Force 4: congenital heart disease: a scientific statement from the American Heart Association and American College of Cardiology,” was prepared by Dr. Van Hare and his colleagues on behalf of the American Heart Association Electrocardiography and Arrhythmias Committee of the Council on Clinical Cardiology, Council on Cardiovascular Disease in the Young, Council on Cardiovascular and Stroke Nursing, Council on Functional Genomics and Translational Biology, and the American College of Cardiology (doi: 10.1016/j.jacc.2015.09.032).

This report is one of the assessments and recommendations of 15 task forces on eligibility and disqualification recommendations for young athletes, nine of which are disease or multidisease related. The other six task forces focus on a variety of relevant topics and issues regarding the risks of young athletes on the field, including screening, the use of automated external defibrillators on the field, the use of dietary supplements and performance-enhancing drugs, sudden death, and the medical-legal perspectives involved.

All 15 task force reports were simultaneously published online in the Journal of the American College of Cardiology and the journal Circulation.

Dr. Van Hare and all but one member of the writing group had no disclosures. One member disclosed consultant/advisory committee associations with a variety of medical device companies.

[email protected]

Most children and young adult patients with congenital heart disease can and should engage in some form of physical activity and should avoid a sedentary lifestyle, according to a task force scientific statement from the American Heart Association and the American College of Cardiology (AHA/ACC).

This recommendation comes despite the fears of sudden cardiac death (SCD) in young athletes, which formed the initial impetus of the entire series of task force reports.

The recommended level of sports participation for patients with treated or untreated congenital heart defect, however, should consider the training and the competitive aspects of the sport itself and must be individualized to the patient. This means taking into account the patient’s current functional status, history of surgery, and the presence of implanted cardiac devices, according to the report by Dr. George F. Van Hare of Washington University, St. Louis, and his colleagues, which was published online in the Journal of the American College of Cardiology.

© Jody Dingle/Fotolia.com

The report breaks down its specific recommendations based upon the various types of congenital heart defect (CHD). Full details and nuances of the recommendations and their specific levels of evidence for each individual condition and the many variants can be found in the online publication. Below is a brief and selected summary for some of the most common defects and some of those most pertinent to sudden cardiac death in young athletes.

Simple shunting lesions (atrial septal defect, ventricular septal defect, patent ductus arteriosus): Treated and untreated

In addressing the three most common subtypes of CHD – ventricular septal defect (VSD, 34%), atrial septal defect (ASD, 13%), and patent ductus arteriosus (PDA, 10%) – the committee found no data that children with these lesions are related to acknowledged episodes of sudden cardiac death (SCD). This applied whether the defects were closed or remained open. “With rare exceptions, patients with hemodynamically insignificant CHD such as VSD, ASD, and PDA may participate competitively in all sports,” it concluded. These recommendations fall under class I; level of evidence C for almost all of these patients, according to the writing committee.

Congenital coronary anomalies: Treated and untreated

Anomalies of coronary arteries are the second-most commonly identified structural causes of SCD in competitive athletes, accounting for about 17% of such deaths in the United States, according to the report. The vast majority of sudden deaths associated with coronary anomalies occur during or shortly after exercise. Despite being less commonly represented in patients, among athletes who have died suddenly, anomalous origin of the left main or left anterior descending coronary artery from the right sinus of Valsalva is far more prevalent. In addition, SCDs are most strongly associated with the pattern in which the anomalous left coronary artery passes between the aorta and main pulmonary artery. Recommended return to intense athletic activities is only to be permitted at least 3 months after surgery, and with a demonstration of the absence of ischemia on postoperative stress testing, with evidence levels depending on the type of anomaly. Of note, in contrast, the committee indicated that athletes with an anomalous origin of a right coronary artery from the left sinus of Valsalva should simply be evaluated by an exercise stress test, and for those without symptoms or a positive exercise stress test, permission to compete can be considered after adequate counseling (class IIa; level of evidence C).

Pulmonary valve stenosis: Treated and untreated

The committee determined that athletes with mild pulmonary stenosis (PS) and normal right ventricular (RV) function can participate in all competitive sports, although annual reevaluation also is recommended (class I; level of evidence B). In addition, athletes treated by operation or balloon valvuloplasty who have achieved adequate relief of PS (gradient less than 40 mm Hg by Doppler) can participate in all competitive sports (class I; level of evidence B). Other patients should be restricted to low-intensity sports, according to the committee.

Aortic valve stenosis: Treated and untreated

Children and adolescents with aortic stenosis (AS) are differentiated between those with mild, moderate, and severe AS by physical examination, ECG, and Doppler echocardiography. In all cases, regardless of the degree of stenosis, patients with a history of fatigue, light-headedness, dizziness, syncope, chest pain, or pallor on exercise deserve a full evaluation. Annual re-evaluation is required for all patients with AS because the disease can progress. Patients with severe AS are at risk of sudden death, particularly with exercise. The committee determined that athletes with mild AS can participate in all competitive sports (class I; level of evidence B), but that athletes with severe AS should be restricted from all competitive sports, with the possible exception of low-intensity sports (class III; level of evidence B).

Coarctation of the aorta: Treated and untreated

Before a decision is made regarding exercise participation, a detailed evaluation should be conducted, including a physical examination, ECG, chest radiograph, exercise testing, transthoracic echocardiographic evaluation of the aortic valve and aorta, and either magnetic resonance imaging or computed tomography angiography, according to the committee. The determination as to the level of sports participation permitted requires a complex assessment of these various test results and can range from full participation in the case of the least affected to restrictions to low-intensity sports in those more severely affected.

Cyanotic CHD, including tetralogy of Fallot

Full clinical assessment, including laboratory and exercise testing, should be considered before any physical activity because this population is at very high risk of sudden death, according to the committee. Recommendations are complex and depend on the level of repair and its success, but, in general, significant restrictions are recommended for all but the most effectively treated patients.

Transposition of the great arteries after atrial switch (Mustard or Senning operation)

This is a population highly at risk, according to the committee. They appear to have a unique response to exercise with reports that a high proportion of sudden death events occur during exertion. In addition, evidence of exercise-induced arrhythmias on routine clinical testing has not been shown to reliably predict exercise-induced SCD events. Although recommendations vary, including strong restrictions for many, at best the most successful of these patients should only be considered for low- to moderate-intensity competitive sports, according to the committee.

Other conditions assessed and evaluated by the committee included congenitally corrected TGA, TGA after the arterial switch, Fontan procedure, elevated pulmonary vascular resistence in CHD, ventricular dysfunction after CHD surgery, and Ebstein anomaly of the tricuspid valve.

In all cases, complete physical assessment of these patients is recommended, especially due to the often highly individualized nature of the patient’s presentation of these conditions and the variety and variability of interventions that may have been performed. Such differentials make recommendations regarding sports participation a complex calculus, which the committee attempts to provide, listing whatever evidence is available.

The majority of these patients, however, will not be considered for the highest levels of competitive sports participation. Although, in almost all cases, the need for physical activity as a contributor to patient health and well-being is stressed at whatever level of performance is possible.

The report ”Eligibility and disqualification recommendations for competitive athletes with cardiovascular abnormalities: Task Force 4: congenital heart disease: a scientific statement from the American Heart Association and American College of Cardiology,” was prepared by Dr. Van Hare and his colleagues on behalf of the American Heart Association Electrocardiography and Arrhythmias Committee of the Council on Clinical Cardiology, Council on Cardiovascular Disease in the Young, Council on Cardiovascular and Stroke Nursing, Council on Functional Genomics and Translational Biology, and the American College of Cardiology (doi: 10.1016/j.jacc.2015.09.032).

This report is one of the assessments and recommendations of 15 task forces on eligibility and disqualification recommendations for young athletes, nine of which are disease or multidisease related. The other six task forces focus on a variety of relevant topics and issues regarding the risks of young athletes on the field, including screening, the use of automated external defibrillators on the field, the use of dietary supplements and performance-enhancing drugs, sudden death, and the medical-legal perspectives involved.

All 15 task force reports were simultaneously published online in the Journal of the American College of Cardiology and the journal Circulation.

Dr. Van Hare and all but one member of the writing group had no disclosures. One member disclosed consultant/advisory committee associations with a variety of medical device companies.

[email protected]

Most children and young adult patients with congenital heart disease can and should engage in some form of physical activity and should avoid a sedentary lifestyle, according to a task force scientific statement from the American Heart Association and the American College of Cardiology (AHA/ACC).

This recommendation comes despite the fears of sudden cardiac death (SCD) in young athletes, which formed the initial impetus of the entire series of task force reports.

The recommended level of sports participation for patients with treated or untreated congenital heart defect, however, should consider the training and the competitive aspects of the sport itself and must be individualized to the patient. This means taking into account the patient’s current functional status, history of surgery, and the presence of implanted cardiac devices, according to the report by Dr. George F. Van Hare of Washington University, St. Louis, and his colleagues, which was published online in the Journal of the American College of Cardiology.

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The report breaks down its specific recommendations based upon the various types of congenital heart defect (CHD). Full details and nuances of the recommendations and their specific levels of evidence for each individual condition and the many variants can be found in the online publication. Below is a brief and selected summary for some of the most common defects and some of those most pertinent to sudden cardiac death in young athletes.

Simple shunting lesions (atrial septal defect, ventricular septal defect, patent ductus arteriosus): Treated and untreated

In addressing the three most common subtypes of CHD – ventricular septal defect (VSD, 34%), atrial septal defect (ASD, 13%), and patent ductus arteriosus (PDA, 10%) – the committee found no data that children with these lesions are related to acknowledged episodes of sudden cardiac death (SCD). This applied whether the defects were closed or remained open. “With rare exceptions, patients with hemodynamically insignificant CHD such as VSD, ASD, and PDA may participate competitively in all sports,” it concluded. These recommendations fall under class I; level of evidence C for almost all of these patients, according to the writing committee.

Congenital coronary anomalies: Treated and untreated

Anomalies of coronary arteries are the second-most commonly identified structural causes of SCD in competitive athletes, accounting for about 17% of such deaths in the United States, according to the report. The vast majority of sudden deaths associated with coronary anomalies occur during or shortly after exercise. Despite being less commonly represented in patients, among athletes who have died suddenly, anomalous origin of the left main or left anterior descending coronary artery from the right sinus of Valsalva is far more prevalent. In addition, SCDs are most strongly associated with the pattern in which the anomalous left coronary artery passes between the aorta and main pulmonary artery. Recommended return to intense athletic activities is only to be permitted at least 3 months after surgery, and with a demonstration of the absence of ischemia on postoperative stress testing, with evidence levels depending on the type of anomaly. Of note, in contrast, the committee indicated that athletes with an anomalous origin of a right coronary artery from the left sinus of Valsalva should simply be evaluated by an exercise stress test, and for those without symptoms or a positive exercise stress test, permission to compete can be considered after adequate counseling (class IIa; level of evidence C).

Pulmonary valve stenosis: Treated and untreated

The committee determined that athletes with mild pulmonary stenosis (PS) and normal right ventricular (RV) function can participate in all competitive sports, although annual reevaluation also is recommended (class I; level of evidence B). In addition, athletes treated by operation or balloon valvuloplasty who have achieved adequate relief of PS (gradient less than 40 mm Hg by Doppler) can participate in all competitive sports (class I; level of evidence B). Other patients should be restricted to low-intensity sports, according to the committee.

Aortic valve stenosis: Treated and untreated

Children and adolescents with aortic stenosis (AS) are differentiated between those with mild, moderate, and severe AS by physical examination, ECG, and Doppler echocardiography. In all cases, regardless of the degree of stenosis, patients with a history of fatigue, light-headedness, dizziness, syncope, chest pain, or pallor on exercise deserve a full evaluation. Annual re-evaluation is required for all patients with AS because the disease can progress. Patients with severe AS are at risk of sudden death, particularly with exercise. The committee determined that athletes with mild AS can participate in all competitive sports (class I; level of evidence B), but that athletes with severe AS should be restricted from all competitive sports, with the possible exception of low-intensity sports (class III; level of evidence B).

Coarctation of the aorta: Treated and untreated

Before a decision is made regarding exercise participation, a detailed evaluation should be conducted, including a physical examination, ECG, chest radiograph, exercise testing, transthoracic echocardiographic evaluation of the aortic valve and aorta, and either magnetic resonance imaging or computed tomography angiography, according to the committee. The determination as to the level of sports participation permitted requires a complex assessment of these various test results and can range from full participation in the case of the least affected to restrictions to low-intensity sports in those more severely affected.

Cyanotic CHD, including tetralogy of Fallot

Full clinical assessment, including laboratory and exercise testing, should be considered before any physical activity because this population is at very high risk of sudden death, according to the committee. Recommendations are complex and depend on the level of repair and its success, but, in general, significant restrictions are recommended for all but the most effectively treated patients.

Transposition of the great arteries after atrial switch (Mustard or Senning operation)

This is a population highly at risk, according to the committee. They appear to have a unique response to exercise with reports that a high proportion of sudden death events occur during exertion. In addition, evidence of exercise-induced arrhythmias on routine clinical testing has not been shown to reliably predict exercise-induced SCD events. Although recommendations vary, including strong restrictions for many, at best the most successful of these patients should only be considered for low- to moderate-intensity competitive sports, according to the committee.

Other conditions assessed and evaluated by the committee included congenitally corrected TGA, TGA after the arterial switch, Fontan procedure, elevated pulmonary vascular resistence in CHD, ventricular dysfunction after CHD surgery, and Ebstein anomaly of the tricuspid valve.

In all cases, complete physical assessment of these patients is recommended, especially due to the often highly individualized nature of the patient’s presentation of these conditions and the variety and variability of interventions that may have been performed. Such differentials make recommendations regarding sports participation a complex calculus, which the committee attempts to provide, listing whatever evidence is available.

The majority of these patients, however, will not be considered for the highest levels of competitive sports participation. Although, in almost all cases, the need for physical activity as a contributor to patient health and well-being is stressed at whatever level of performance is possible.

The report ”Eligibility and disqualification recommendations for competitive athletes with cardiovascular abnormalities: Task Force 4: congenital heart disease: a scientific statement from the American Heart Association and American College of Cardiology,” was prepared by Dr. Van Hare and his colleagues on behalf of the American Heart Association Electrocardiography and Arrhythmias Committee of the Council on Clinical Cardiology, Council on Cardiovascular Disease in the Young, Council on Cardiovascular and Stroke Nursing, Council on Functional Genomics and Translational Biology, and the American College of Cardiology (doi: 10.1016/j.jacc.2015.09.032).

This report is one of the assessments and recommendations of 15 task forces on eligibility and disqualification recommendations for young athletes, nine of which are disease or multidisease related. The other six task forces focus on a variety of relevant topics and issues regarding the risks of young athletes on the field, including screening, the use of automated external defibrillators on the field, the use of dietary supplements and performance-enhancing drugs, sudden death, and the medical-legal perspectives involved.

All 15 task force reports were simultaneously published online in the Journal of the American College of Cardiology and the journal Circulation.

Dr. Van Hare and all but one member of the writing group had no disclosures. One member disclosed consultant/advisory committee associations with a variety of medical device companies.

[email protected]