Mitchel L. Zoler, PhD

CHICAGO - Last fall, physicians at Vanderbilt University Medical Center began routinely testing all patients who were scheduled for coronary catheterization with a broad genotyping screen that - among other things - would identify whether they had a problem activating clopidogrel. By mid-November, the program had tested about 300 patients, including 10 found to have a poor-metabolizer genotype in the hepatic-enzyme gene CYP2C19 that would likely blunt the efficacy of a conventional clopidogrel dose. Many of the 10 patients received a doubled dose to compensate, whereas others who weren't aged 75 or older received the pricier, alternative agent prasugrel.

This experience marked the first phase of a new Vanderbilt program that will expand over time to include other patients in line to receive a drug with a pharmacogenetic dimension, Dr. Dan M. Roden said at the meeting. The genotyping program will soon expand to include patients who are scheduled for knee- or hip-replacement surgery, anticipating their need to start on warfarin. Genotype data can also help physicians select the best dosage for starting a warfarin regimen, said Dr. Roden, a cardiologist and assistant vice chancellor for personalized medicine at Vanderbilt in Nashville, Tenn.

Subsequent expansion plans are not yet set, but other candidates for genotyping include patients who are either already on or at an increased risk for soon starting tamoxifen, abacavir, azathioprine, 6-mercaptopurine, codeine, or "virtually any antidepressant or most antipsychotics,” Dr. Roden said in an interview.

"In the long perspective, every 50-year-old” is a good bet to eventually receive at least one drug for which a dosage adjustment based on genotype is warranted, but - stopping short of such global use right now - the Vanderbilt program will instead gradually phase in new groups of patients to the offer of genotyping.

"Implementation is a huge challenge. In my opinion, this will only work with preemptive implementation. Electronic records are not just repositories of information, but are nimble enough to provide support at the time of a prescription,” he said. "The way it ought to work is, a physician prescribes a drug and the electronic system recognizes [that] the drug has a genetic element and goes into the patient's record and finds the genotype information” to decide whether to flash a screen alert about the patient's genotype and the implications.

The program, known as PREDICT (Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment) launched on Sept. 15. It uses a genotyping panel sold on the U.S. market by Illumina that screens for 184 different genetic polymorphisms in 34 genes that affect the absorption, distribution, metabolism, or excretion of various drugs.

Test results get posted into the record within a day of specimen collection.

So far, Vanderbilt itself has completely funded the program, which involved a year of planning and "a huge amount of money,” said Dr. Roden, adding that the program is the first of its kind worldwide. PREDICT is expected to improve patient outcomes and its developers hope to eventually convince payers to cover the cost.

Dr. Roden stated that he is or has been a consultant to several drug companies and has received royalties from Clinical Data Inc.

CHICAGO - Last fall, physicians at Vanderbilt University Medical Center began routinely testing all patients who were scheduled for coronary catheterization with a broad genotyping screen that - among other things - would identify whether they had a problem activating clopidogrel. By mid-November, the program had tested about 300 patients, including 10 found to have a poor-metabolizer genotype in the hepatic-enzyme gene CYP2C19 that would likely blunt the efficacy of a conventional clopidogrel dose. Many of the 10 patients received a doubled dose to compensate, whereas others who weren't aged 75 or older received the pricier, alternative agent prasugrel.

This experience marked the first phase of a new Vanderbilt program that will expand over time to include other patients in line to receive a drug with a pharmacogenetic dimension, Dr. Dan M. Roden said at the meeting. The genotyping program will soon expand to include patients who are scheduled for knee- or hip-replacement surgery, anticipating their need to start on warfarin. Genotype data can also help physicians select the best dosage for starting a warfarin regimen, said Dr. Roden, a cardiologist and assistant vice chancellor for personalized medicine at Vanderbilt in Nashville, Tenn.

Subsequent expansion plans are not yet set, but other candidates for genotyping include patients who are either already on or at an increased risk for soon starting tamoxifen, abacavir, azathioprine, 6-mercaptopurine, codeine, or "virtually any antidepressant or most antipsychotics,” Dr. Roden said in an interview.

"In the long perspective, every 50-year-old” is a good bet to eventually receive at least one drug for which a dosage adjustment based on genotype is warranted, but - stopping short of such global use right now - the Vanderbilt program will instead gradually phase in new groups of patients to the offer of genotyping.

"Implementation is a huge challenge. In my opinion, this will only work with preemptive implementation. Electronic records are not just repositories of information, but are nimble enough to provide support at the time of a prescription,” he said. "The way it ought to work is, a physician prescribes a drug and the electronic system recognizes [that] the drug has a genetic element and goes into the patient's record and finds the genotype information” to decide whether to flash a screen alert about the patient's genotype and the implications.

The program, known as PREDICT (Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment) launched on Sept. 15. It uses a genotyping panel sold on the U.S. market by Illumina that screens for 184 different genetic polymorphisms in 34 genes that affect the absorption, distribution, metabolism, or excretion of various drugs.

Test results get posted into the record within a day of specimen collection.

So far, Vanderbilt itself has completely funded the program, which involved a year of planning and "a huge amount of money,” said Dr. Roden, adding that the program is the first of its kind worldwide. PREDICT is expected to improve patient outcomes and its developers hope to eventually convince payers to cover the cost.

Dr. Roden stated that he is or has been a consultant to several drug companies and has received royalties from Clinical Data Inc.

CHICAGO - Last fall, physicians at Vanderbilt University Medical Center began routinely testing all patients who were scheduled for coronary catheterization with a broad genotyping screen that - among other things - would identify whether they had a problem activating clopidogrel. By mid-November, the program had tested about 300 patients, including 10 found to have a poor-metabolizer genotype in the hepatic-enzyme gene CYP2C19 that would likely blunt the efficacy of a conventional clopidogrel dose. Many of the 10 patients received a doubled dose to compensate, whereas others who weren't aged 75 or older received the pricier, alternative agent prasugrel.

This experience marked the first phase of a new Vanderbilt program that will expand over time to include other patients in line to receive a drug with a pharmacogenetic dimension, Dr. Dan M. Roden said at the meeting. The genotyping program will soon expand to include patients who are scheduled for knee- or hip-replacement surgery, anticipating their need to start on warfarin. Genotype data can also help physicians select the best dosage for starting a warfarin regimen, said Dr. Roden, a cardiologist and assistant vice chancellor for personalized medicine at Vanderbilt in Nashville, Tenn.

Subsequent expansion plans are not yet set, but other candidates for genotyping include patients who are either already on or at an increased risk for soon starting tamoxifen, abacavir, azathioprine, 6-mercaptopurine, codeine, or "virtually any antidepressant or most antipsychotics,” Dr. Roden said in an interview.

"In the long perspective, every 50-year-old” is a good bet to eventually receive at least one drug for which a dosage adjustment based on genotype is warranted, but - stopping short of such global use right now - the Vanderbilt program will instead gradually phase in new groups of patients to the offer of genotyping.

"Implementation is a huge challenge. In my opinion, this will only work with preemptive implementation. Electronic records are not just repositories of information, but are nimble enough to provide support at the time of a prescription,” he said. "The way it ought to work is, a physician prescribes a drug and the electronic system recognizes [that] the drug has a genetic element and goes into the patient's record and finds the genotype information” to decide whether to flash a screen alert about the patient's genotype and the implications.

The program, known as PREDICT (Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment) launched on Sept. 15. It uses a genotyping panel sold on the U.S. market by Illumina that screens for 184 different genetic polymorphisms in 34 genes that affect the absorption, distribution, metabolism, or excretion of various drugs.

Test results get posted into the record within a day of specimen collection.

So far, Vanderbilt itself has completely funded the program, which involved a year of planning and "a huge amount of money,” said Dr. Roden, adding that the program is the first of its kind worldwide. PREDICT is expected to improve patient outcomes and its developers hope to eventually convince payers to cover the cost.

Dr. Roden stated that he is or has been a consultant to several drug companies and has received royalties from Clinical Data Inc.

CHICAGO - Last fall, physicians at Vanderbilt University Medical Center began routinely testing all patients who were scheduled for coronary catheterization with a broad genotyping screen that - among other things - would identify whether they had a problem activating clopidogrel. By mid-November, the program had tested about 300 patients, including 10 found to have a poor-metabolizer genotype in the hepatic-enzyme gene CYP2C19 that would likely blunt the efficacy of a conventional clopidogrel dose. Many of the 10 patients received a doubled dose to compensate, whereas others who weren't aged 75 or older received the pricier, alternative agent prasugrel.

This experience marked the first phase of a new Vanderbilt program that will expand over time to include other patients in line to receive a drug with a pharmacogenetic dimension, Dr. Dan M. Roden said at the meeting. The genotyping program will soon expand to include patients who are scheduled for knee- or hip-replacement surgery, anticipating their need to start on warfarin. Genotype data can also help physicians select the best dosage for starting a warfarin regimen, said Dr. Roden, a cardiologist and assistant vice chancellor for personalized medicine at Vanderbilt in Nashville, Tenn.

Subsequent expansion plans are not yet set, but other candidates for genotyping include patients who are either already on or at an increased risk for soon starting tamoxifen, abacavir, azathioprine, 6-mercaptopurine, codeine, or "virtually any antidepressant or most antipsychotics,” Dr. Roden said in an interview.

"In the long perspective, every 50-year-old” is a good bet to eventually receive at least one drug for which a dosage adjustment based on genotype is warranted, but - stopping short of such global use right now - the Vanderbilt program will instead gradually phase in new groups of patients to the offer of genotyping.

"Implementation is a huge challenge. In my opinion, this will only work with preemptive implementation. Electronic records are not just repositories of information, but are nimble enough to provide support at the time of a prescription,” he said. "The way it ought to work is, a physician prescribes a drug and the electronic system recognizes [that] the drug has a genetic element and goes into the patient's record and finds the genotype information” to decide whether to flash a screen alert about the patient's genotype and the implications.

The program, known as PREDICT (Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment) launched on Sept. 15. It uses a genotyping panel sold on the U.S. market by Illumina that screens for 184 different genetic polymorphisms in 34 genes that affect the absorption, distribution, metabolism, or excretion of various drugs.

Test results get posted into the record within a day of specimen collection.

So far, Vanderbilt itself has completely funded the program, which involved a year of planning and "a huge amount of money,” said Dr. Roden, adding that the program is the first of its kind worldwide. PREDICT is expected to improve patient outcomes and its developers hope to eventually convince payers to cover the cost.

Dr. Roden stated that he is or has been a consultant to several drug companies and has received royalties from Clinical Data Inc.

CHICAGO - Last fall, physicians at Vanderbilt University Medical Center began routinely testing all patients who were scheduled for coronary catheterization with a broad genotyping screen that - among other things - would identify whether they had a problem activating clopidogrel. By mid-November, the program had tested about 300 patients, including 10 found to have a poor-metabolizer genotype in the hepatic-enzyme gene CYP2C19 that would likely blunt the efficacy of a conventional clopidogrel dose. Many of the 10 patients received a doubled dose to compensate, whereas others who weren't aged 75 or older received the pricier, alternative agent prasugrel.

This experience marked the first phase of a new Vanderbilt program that will expand over time to include other patients in line to receive a drug with a pharmacogenetic dimension, Dr. Dan M. Roden said at the meeting. The genotyping program will soon expand to include patients who are scheduled for knee- or hip-replacement surgery, anticipating their need to start on warfarin. Genotype data can also help physicians select the best dosage for starting a warfarin regimen, said Dr. Roden, a cardiologist and assistant vice chancellor for personalized medicine at Vanderbilt in Nashville, Tenn.

Subsequent expansion plans are not yet set, but other candidates for genotyping include patients who are either already on or at an increased risk for soon starting tamoxifen, abacavir, azathioprine, 6-mercaptopurine, codeine, or "virtually any antidepressant or most antipsychotics,” Dr. Roden said in an interview.

"In the long perspective, every 50-year-old” is a good bet to eventually receive at least one drug for which a dosage adjustment based on genotype is warranted, but - stopping short of such global use right now - the Vanderbilt program will instead gradually phase in new groups of patients to the offer of genotyping.

"Implementation is a huge challenge. In my opinion, this will only work with preemptive implementation. Electronic records are not just repositories of information, but are nimble enough to provide support at the time of a prescription,” he said. "The way it ought to work is, a physician prescribes a drug and the electronic system recognizes [that] the drug has a genetic element and goes into the patient's record and finds the genotype information” to decide whether to flash a screen alert about the patient's genotype and the implications.

The program, known as PREDICT (Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment) launched on Sept. 15. It uses a genotyping panel sold on the U.S. market by Illumina that screens for 184 different genetic polymorphisms in 34 genes that affect the absorption, distribution, metabolism, or excretion of various drugs.

Test results get posted into the record within a day of specimen collection.

So far, Vanderbilt itself has completely funded the program, which involved a year of planning and "a huge amount of money,” said Dr. Roden, adding that the program is the first of its kind worldwide. PREDICT is expected to improve patient outcomes and its developers hope to eventually convince payers to cover the cost.

Dr. Roden stated that he is or has been a consultant to several drug companies and has received royalties from Clinical Data Inc.

CHICAGO - Last fall, physicians at Vanderbilt University Medical Center began routinely testing all patients who were scheduled for coronary catheterization with a broad genotyping screen that - among other things - would identify whether they had a problem activating clopidogrel. By mid-November, the program had tested about 300 patients, including 10 found to have a poor-metabolizer genotype in the hepatic-enzyme gene CYP2C19 that would likely blunt the efficacy of a conventional clopidogrel dose. Many of the 10 patients received a doubled dose to compensate, whereas others who weren't aged 75 or older received the pricier, alternative agent prasugrel.

This experience marked the first phase of a new Vanderbilt program that will expand over time to include other patients in line to receive a drug with a pharmacogenetic dimension, Dr. Dan M. Roden said at the meeting. The genotyping program will soon expand to include patients who are scheduled for knee- or hip-replacement surgery, anticipating their need to start on warfarin. Genotype data can also help physicians select the best dosage for starting a warfarin regimen, said Dr. Roden, a cardiologist and assistant vice chancellor for personalized medicine at Vanderbilt in Nashville, Tenn.

Subsequent expansion plans are not yet set, but other candidates for genotyping include patients who are either already on or at an increased risk for soon starting tamoxifen, abacavir, azathioprine, 6-mercaptopurine, codeine, or "virtually any antidepressant or most antipsychotics,” Dr. Roden said in an interview.

"In the long perspective, every 50-year-old” is a good bet to eventually receive at least one drug for which a dosage adjustment based on genotype is warranted, but - stopping short of such global use right now - the Vanderbilt program will instead gradually phase in new groups of patients to the offer of genotyping.

"Implementation is a huge challenge. In my opinion, this will only work with preemptive implementation. Electronic records are not just repositories of information, but are nimble enough to provide support at the time of a prescription,” he said. "The way it ought to work is, a physician prescribes a drug and the electronic system recognizes [that] the drug has a genetic element and goes into the patient's record and finds the genotype information” to decide whether to flash a screen alert about the patient's genotype and the implications.

The program, known as PREDICT (Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment) launched on Sept. 15. It uses a genotyping panel sold on the U.S. market by Illumina that screens for 184 different genetic polymorphisms in 34 genes that affect the absorption, distribution, metabolism, or excretion of various drugs.

Test results get posted into the record within a day of specimen collection.

So far, Vanderbilt itself has completely funded the program, which involved a year of planning and "a huge amount of money,” said Dr. Roden, adding that the program is the first of its kind worldwide. PREDICT is expected to improve patient outcomes and its developers hope to eventually convince payers to cover the cost.

Dr. Roden stated that he is or has been a consultant to several drug companies and has received royalties from Clinical Data Inc.

Major Finding: Six-year-old children from low socioeconomic families and born to mothers who had gestational diabetes had a ninefold increased rate of diagnosis for attention-deficit/hyperactivity disorder, compared with children from higher socioeconomic families whose mothers did not have gestational diabetes.

Data Source: Multicenter study of 216 children, 9 of whom came from low socioeconomic families and were born to mothers who had gestational diabetes.

Disclosures: Ms. Jordan had no relevant financial disclosures.

NEW YORK – Children born to mothers with gestational diabetes during pregnancy had a significantly increased risk of developing attention-deficit/hyperactivity disorder when they reached 6 years old, based on a study with 216 children.

The risk was even greater in children of families with low socioeconomic status. The combined effect of gestational diabetes and low socioeconomic status was linked with a statistically significant, ninefold increased rate of attention-deficit/hyperactivity disorder (ADHD) in children when they reached age 6 years, Alexandra S. Jordan reported in a poster at the meeting.

The findings “raise the possibility that manifestations of ADHD are not simply genetically mediated. Rather, susceptibility may increase as a function of the uterine environment (as with gestational diabetes) and may be further aggravated as a result of socioeconomic hardship during childhood,” Ms. Jordan and her associates reported in their poster.

Prior published reports had identified both gestational diabetes and low socioeconomic status as risk factors for the subsequent development of ADHD in young children.

But in this study, when the researchers looked at the impact of both factors together, “something bizarre happened.” The risk increased “way beyond the expected impact,” Ms. Jordan said in an interview. She and her colleagues do not currently have an explanation for this apparent synergistic interaction.

The study assessed 216 unselected children for ADHD symptoms at age 4 years and for a diagnosis of ADHD at age 6 years. The mothers of 21 of the children had gestational diabetes during pregnancy, and this subgroup had a 2.19-fold increased risk for having a diagnosis of ADHD at age 6 years, compared with the children born to mothers who never had gestational diabetes.

In addition, 104 of the children came from low socioeconomic status households, and these children had a 2.05-fold increased rate of having ADHD, compared with the other children from higher socioeconomic families, said Ms. Jordan, a researcher in the department of counseling and clinical psychology at Columbia University in New York.

The group included nine children whose mother had gestational diabetes and who came from low socioeconomic family.

In this subgroup, the prevalence of the ADHD diagnosis at age 6 years was 9.23-fold higher than it was for the children whose mothers did not have gestational diabetes and who came from families with higher socioeconomic status.

The apparent effect of gestational diabetes and low socioeconomic status on ADHD prevalence remained statistically significant after researchers adjusted for whether one or both parents had ADHD.

“These findings may be useful in educating women considering pregnancy, particularly those in low socioeconomic environments, about the potential lingering effects of gestational diabetes on offspring into childhood,” the researchers said in their poster.

“This information may encourage women to control gestational diabetes symptoms during pregnancy.” In addition, it may help “educate health care providers on the importance of assessment and control of gestational diabetes symptoms throughout pregnancy and on ADHD's etiologic link to gestational diabetes.” The findings might also help “target early interventions to those low socioeconomic status families who are most vulnerable” to this interaction with gestational diabetes, they said.

Major Finding: Six-year-old children from low socioeconomic families and born to mothers who had gestational diabetes had a ninefold increased rate of diagnosis for attention-deficit/hyperactivity disorder, compared with children from higher socioeconomic families whose mothers did not have gestational diabetes.

Data Source: Multicenter study of 216 children, 9 of whom came from low socioeconomic families and were born to mothers who had gestational diabetes.

Disclosures: Ms. Jordan had no relevant financial disclosures.

NEW YORK – Children born to mothers with gestational diabetes during pregnancy had a significantly increased risk of developing attention-deficit/hyperactivity disorder when they reached 6 years old, based on a study with 216 children.

The risk was even greater in children of families with low socioeconomic status. The combined effect of gestational diabetes and low socioeconomic status was linked with a statistically significant, ninefold increased rate of attention-deficit/hyperactivity disorder (ADHD) in children when they reached age 6 years, Alexandra S. Jordan reported in a poster at the meeting.

The findings “raise the possibility that manifestations of ADHD are not simply genetically mediated. Rather, susceptibility may increase as a function of the uterine environment (as with gestational diabetes) and may be further aggravated as a result of socioeconomic hardship during childhood,” Ms. Jordan and her associates reported in their poster.

Prior published reports had identified both gestational diabetes and low socioeconomic status as risk factors for the subsequent development of ADHD in young children.

But in this study, when the researchers looked at the impact of both factors together, “something bizarre happened.” The risk increased “way beyond the expected impact,” Ms. Jordan said in an interview. She and her colleagues do not currently have an explanation for this apparent synergistic interaction.

The study assessed 216 unselected children for ADHD symptoms at age 4 years and for a diagnosis of ADHD at age 6 years. The mothers of 21 of the children had gestational diabetes during pregnancy, and this subgroup had a 2.19-fold increased risk for having a diagnosis of ADHD at age 6 years, compared with the children born to mothers who never had gestational diabetes.

In addition, 104 of the children came from low socioeconomic status households, and these children had a 2.05-fold increased rate of having ADHD, compared with the other children from higher socioeconomic families, said Ms. Jordan, a researcher in the department of counseling and clinical psychology at Columbia University in New York.

The group included nine children whose mother had gestational diabetes and who came from low socioeconomic family.

In this subgroup, the prevalence of the ADHD diagnosis at age 6 years was 9.23-fold higher than it was for the children whose mothers did not have gestational diabetes and who came from families with higher socioeconomic status.

The apparent effect of gestational diabetes and low socioeconomic status on ADHD prevalence remained statistically significant after researchers adjusted for whether one or both parents had ADHD.

“These findings may be useful in educating women considering pregnancy, particularly those in low socioeconomic environments, about the potential lingering effects of gestational diabetes on offspring into childhood,” the researchers said in their poster.

“This information may encourage women to control gestational diabetes symptoms during pregnancy.” In addition, it may help “educate health care providers on the importance of assessment and control of gestational diabetes symptoms throughout pregnancy and on ADHD's etiologic link to gestational diabetes.” The findings might also help “target early interventions to those low socioeconomic status families who are most vulnerable” to this interaction with gestational diabetes, they said.

Major Finding: Six-year-old children from low socioeconomic families and born to mothers who had gestational diabetes had a ninefold increased rate of diagnosis for attention-deficit/hyperactivity disorder, compared with children from higher socioeconomic families whose mothers did not have gestational diabetes.

Data Source: Multicenter study of 216 children, 9 of whom came from low socioeconomic families and were born to mothers who had gestational diabetes.

Disclosures: Ms. Jordan had no relevant financial disclosures.

NEW YORK – Children born to mothers with gestational diabetes during pregnancy had a significantly increased risk of developing attention-deficit/hyperactivity disorder when they reached 6 years old, based on a study with 216 children.

The risk was even greater in children of families with low socioeconomic status. The combined effect of gestational diabetes and low socioeconomic status was linked with a statistically significant, ninefold increased rate of attention-deficit/hyperactivity disorder (ADHD) in children when they reached age 6 years, Alexandra S. Jordan reported in a poster at the meeting.

The findings “raise the possibility that manifestations of ADHD are not simply genetically mediated. Rather, susceptibility may increase as a function of the uterine environment (as with gestational diabetes) and may be further aggravated as a result of socioeconomic hardship during childhood,” Ms. Jordan and her associates reported in their poster.

Prior published reports had identified both gestational diabetes and low socioeconomic status as risk factors for the subsequent development of ADHD in young children.

But in this study, when the researchers looked at the impact of both factors together, “something bizarre happened.” The risk increased “way beyond the expected impact,” Ms. Jordan said in an interview. She and her colleagues do not currently have an explanation for this apparent synergistic interaction.

The study assessed 216 unselected children for ADHD symptoms at age 4 years and for a diagnosis of ADHD at age 6 years. The mothers of 21 of the children had gestational diabetes during pregnancy, and this subgroup had a 2.19-fold increased risk for having a diagnosis of ADHD at age 6 years, compared with the children born to mothers who never had gestational diabetes.

In addition, 104 of the children came from low socioeconomic status households, and these children had a 2.05-fold increased rate of having ADHD, compared with the other children from higher socioeconomic families, said Ms. Jordan, a researcher in the department of counseling and clinical psychology at Columbia University in New York.

The group included nine children whose mother had gestational diabetes and who came from low socioeconomic family.

In this subgroup, the prevalence of the ADHD diagnosis at age 6 years was 9.23-fold higher than it was for the children whose mothers did not have gestational diabetes and who came from families with higher socioeconomic status.

The apparent effect of gestational diabetes and low socioeconomic status on ADHD prevalence remained statistically significant after researchers adjusted for whether one or both parents had ADHD.

“These findings may be useful in educating women considering pregnancy, particularly those in low socioeconomic environments, about the potential lingering effects of gestational diabetes on offspring into childhood,” the researchers said in their poster.

“This information may encourage women to control gestational diabetes symptoms during pregnancy.” In addition, it may help “educate health care providers on the importance of assessment and control of gestational diabetes symptoms throughout pregnancy and on ADHD's etiologic link to gestational diabetes.” The findings might also help “target early interventions to those low socioeconomic status families who are most vulnerable” to this interaction with gestational diabetes, they said.

CHICAGO – Last fall, physicians at Vanderbilt University Medical Center began routinely testing all patients who were scheduled for coronary catheterization with a broad genotyping screen that – among other things – would identify whether they had a problem activating clopidogrel.

By mid-November, the program had tested about 300 patients, including 10 found to have a poor-metabolizer genotype in the hepatic-enzyme gene CYP2C19 that would likely blunt the efficacy of a conventional clopidogrel dose. Many of the 10 patients received a doubled dose to compensate, whereas others who weren't aged 75 or older received the pricier, alternative agent prasugrel.

This experience marked the first phase of a new Vanderbilt program that will expand over time to include other patients in line to receive a drug with a pharmacogenetic dimension, Dr. Dan M. Roden said at the meeting.

The genotyping program will soon expand to include patients who are scheduled for knee- or hip-replacement surgery, anticipating their need to start on warfarin. Genotype data can also help physicians select the best dosage for starting a warfarin regimen, said Dr. Roden, a cardiologist and assistant vice chancellor for personalized medicine at Vanderbilt in Nashville, Tenn.

Subsequent expansion plans are not yet set, but other candidates for genotyping include patients who are either already on or at an increased risk for soon starting tamoxifen, abacavir, azathioprine, 6-mercaptopurine, codeine, or “virtually any antidepressant or most antipsychotics,” Dr. Roden said in an interview.

“In the long perspective, every 50-year-old” is a good bet to eventually receive at least one drug for which a dosage adjustment based on genotype is warranted, but – stopping short of such global use right now – the Vanderbilt program will instead gradually phase in new groups of patients to the offer of genotyping.

“Implementation is a huge challenge. In my opinion, this will only work with preemptive implementation. Electronic records are not just repositories of information, but are nimble enough to provide support at the time of a prescription,” he said. “The way it ought to work is, a physician prescribes a drug and the electronic system recognizes [that] the drug has a genetic element and goes into the patient's record and finds the genotype information” to decide whether to flash a screen alert about the patient's genotype and the implications.

The program, known as PREDICT (Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment) launched on Sept. 15.

It uses a genotyping panel sold on the U.S. market by Illumina that screens for 184 different genetic polymorphisms in 34 genes that affect the absorption, distribution, metabolism, or excretion of various drugs. Test results get posted into the record within a day of specimen collection.

So far, Vanderbilt itself has completely funded the program, which involved a year of planning and “a huge amount of money,” said Dr. Roden, adding that the program is the first of its kind worldwide.

PREDICT is expected to improve patient outcomes, and its developers hope to eventually convince payers to cover the cost.

Dr. Roden reported that he is or has been a consultant to Merck, Novartis, Sanofi-Aventis, Daiichi Sankyo, and Astellas and has received royalties from Clinical Data.

Scyble Van Cleve, right, is the first patient at Vanderbilt to benefit from a program that helps physicians like Dr. John McPherson choose the best drug and dose.

Source Courtesy Susan Urmy

The program identified 10 patients whose genotype would likely blunt the efficacy of clopidogrel.

Source DR. RODEN

CHICAGO – Last fall, physicians at Vanderbilt University Medical Center began routinely testing all patients who were scheduled for coronary catheterization with a broad genotyping screen that – among other things – would identify whether they had a problem activating clopidogrel.

By mid-November, the program had tested about 300 patients, including 10 found to have a poor-metabolizer genotype in the hepatic-enzyme gene CYP2C19 that would likely blunt the efficacy of a conventional clopidogrel dose. Many of the 10 patients received a doubled dose to compensate, whereas others who weren't aged 75 or older received the pricier, alternative agent prasugrel.

This experience marked the first phase of a new Vanderbilt program that will expand over time to include other patients in line to receive a drug with a pharmacogenetic dimension, Dr. Dan M. Roden said at the meeting.

The genotyping program will soon expand to include patients who are scheduled for knee- or hip-replacement surgery, anticipating their need to start on warfarin. Genotype data can also help physicians select the best dosage for starting a warfarin regimen, said Dr. Roden, a cardiologist and assistant vice chancellor for personalized medicine at Vanderbilt in Nashville, Tenn.

Subsequent expansion plans are not yet set, but other candidates for genotyping include patients who are either already on or at an increased risk for soon starting tamoxifen, abacavir, azathioprine, 6-mercaptopurine, codeine, or “virtually any antidepressant or most antipsychotics,” Dr. Roden said in an interview.

“In the long perspective, every 50-year-old” is a good bet to eventually receive at least one drug for which a dosage adjustment based on genotype is warranted, but – stopping short of such global use right now – the Vanderbilt program will instead gradually phase in new groups of patients to the offer of genotyping.

“Implementation is a huge challenge. In my opinion, this will only work with preemptive implementation. Electronic records are not just repositories of information, but are nimble enough to provide support at the time of a prescription,” he said. “The way it ought to work is, a physician prescribes a drug and the electronic system recognizes [that] the drug has a genetic element and goes into the patient's record and finds the genotype information” to decide whether to flash a screen alert about the patient's genotype and the implications.

The program, known as PREDICT (Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment) launched on Sept. 15.

It uses a genotyping panel sold on the U.S. market by Illumina that screens for 184 different genetic polymorphisms in 34 genes that affect the absorption, distribution, metabolism, or excretion of various drugs. Test results get posted into the record within a day of specimen collection.

So far, Vanderbilt itself has completely funded the program, which involved a year of planning and “a huge amount of money,” said Dr. Roden, adding that the program is the first of its kind worldwide.

PREDICT is expected to improve patient outcomes, and its developers hope to eventually convince payers to cover the cost.

Dr. Roden reported that he is or has been a consultant to Merck, Novartis, Sanofi-Aventis, Daiichi Sankyo, and Astellas and has received royalties from Clinical Data.

Scyble Van Cleve, right, is the first patient at Vanderbilt to benefit from a program that helps physicians like Dr. John McPherson choose the best drug and dose.

Source Courtesy Susan Urmy

The program identified 10 patients whose genotype would likely blunt the efficacy of clopidogrel.

Source DR. RODEN

CHICAGO – Last fall, physicians at Vanderbilt University Medical Center began routinely testing all patients who were scheduled for coronary catheterization with a broad genotyping screen that – among other things – would identify whether they had a problem activating clopidogrel.

By mid-November, the program had tested about 300 patients, including 10 found to have a poor-metabolizer genotype in the hepatic-enzyme gene CYP2C19 that would likely blunt the efficacy of a conventional clopidogrel dose. Many of the 10 patients received a doubled dose to compensate, whereas others who weren't aged 75 or older received the pricier, alternative agent prasugrel.

This experience marked the first phase of a new Vanderbilt program that will expand over time to include other patients in line to receive a drug with a pharmacogenetic dimension, Dr. Dan M. Roden said at the meeting.

The genotyping program will soon expand to include patients who are scheduled for knee- or hip-replacement surgery, anticipating their need to start on warfarin. Genotype data can also help physicians select the best dosage for starting a warfarin regimen, said Dr. Roden, a cardiologist and assistant vice chancellor for personalized medicine at Vanderbilt in Nashville, Tenn.

Subsequent expansion plans are not yet set, but other candidates for genotyping include patients who are either already on or at an increased risk for soon starting tamoxifen, abacavir, azathioprine, 6-mercaptopurine, codeine, or “virtually any antidepressant or most antipsychotics,” Dr. Roden said in an interview.

“In the long perspective, every 50-year-old” is a good bet to eventually receive at least one drug for which a dosage adjustment based on genotype is warranted, but – stopping short of such global use right now – the Vanderbilt program will instead gradually phase in new groups of patients to the offer of genotyping.

“Implementation is a huge challenge. In my opinion, this will only work with preemptive implementation. Electronic records are not just repositories of information, but are nimble enough to provide support at the time of a prescription,” he said. “The way it ought to work is, a physician prescribes a drug and the electronic system recognizes [that] the drug has a genetic element and goes into the patient's record and finds the genotype information” to decide whether to flash a screen alert about the patient's genotype and the implications.

The program, known as PREDICT (Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment) launched on Sept. 15.

It uses a genotyping panel sold on the U.S. market by Illumina that screens for 184 different genetic polymorphisms in 34 genes that affect the absorption, distribution, metabolism, or excretion of various drugs. Test results get posted into the record within a day of specimen collection.

So far, Vanderbilt itself has completely funded the program, which involved a year of planning and “a huge amount of money,” said Dr. Roden, adding that the program is the first of its kind worldwide.

PREDICT is expected to improve patient outcomes, and its developers hope to eventually convince payers to cover the cost.

Dr. Roden reported that he is or has been a consultant to Merck, Novartis, Sanofi-Aventis, Daiichi Sankyo, and Astellas and has received royalties from Clinical Data.

Scyble Van Cleve, right, is the first patient at Vanderbilt to benefit from a program that helps physicians like Dr. John McPherson choose the best drug and dose.

Source Courtesy Susan Urmy

The program identified 10 patients whose genotype would likely blunt the efficacy of clopidogrel.

Source DR. RODEN

Major Finding: Survey results showed that 36% of responding interventional cardiologists routinely use aspiration thrombectomy when treating patients with an acute ST-segment elevation myocardial infarction.

Data Source: Internet-based survey with responses from 477 interventional cardiologists worldwide.

Disclosures: TOTAL is using the Export catheter, which is marketed by Medtronic. Medtronic is cofunding this trial along with the Canadian Network and Centre for Trials Internationally. Dr. Jolly said that he has received grant support from Medtronic, and has received speakers' honoraria from GlaxoSmithKline, Sanofi-Aventis, and Boehringer Ingelheim.

CHICAGO – Most interventional cardiologists remain wary of using thrombus aspiration as initial treatment for an acute myocardial infarction, despite the striking mortality benefit reported for this approach in a single-center study more than 2 years ago.

“Interventional cardiologists feel that a definitive randomized, controlled trial is needed,” according to results from an Internet-based survey with responses from 477 interventionalists, Dr. Sanjit S. Jolly said at the meeting.

Based in part on the equipoise the survey revealed among interventionalists between aspiration thrombectomy followed by percutaneous coronary intervention (PCI), and PCI alone, for treating an acute myocardial infarction, Dr. Jolly said that he and his associates began TOTAL, a multicenter Trial of Routine Aspiration Thrombectomy With Percutaneous Coronary Intervention versus PCI Alone in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary PCI.

The researchers designed TOTAL to randomize 4,000 patients, said Dr. Jolly, a cardiologist at McMaster University in Hamilton, Ont. He said they hope to have the study completed within the next 2 years.

Aspiration thrombectomy as initial treatment for an acute ST-segment elevation myocardial infarction burst onto the scene in June 2008 with the publication of results from the Thrombus Aspiration During Percutaneous Coronary Intervention in Acute Myocardial Infarction Study (TAPAS), which involved 1,071 patients treated at the University Medical Center Groningen (the Netherlands).

In that study, at 1 year after treatment, the rate of cardiac death reached 3.6% in the patients randomized to thrombectomy plus PCI and 6.7% in those treated by standard PCI alone. The difference was statistically significant (Lancet 2008;371:1915-20).

This “unexpected” substantial advantage in favor of thrombectomy “created a lot of press,” Dr. Jolly commented.

However, a subsequent meta-analysis of thrombectomy for treating acute myocardial infarctions that included 21 studies (including the results from TAPAS) with a total of nearly 4,300 patients failed to find that adding thrombectomy led to a significant improvement in survival compared with primary PCI alone (Circ. Cardiovasc. Interv. 2010;3:6-16).

To get a better sense of the worldwide use of thrombectomy, Dr. Jolly and his associates distributed their survey to 1,651 interventionalists worldwide and received 477 responses. The results showed that 36% of respondents reported using thrombectomy routinely along with PCI when treating patients with an acute ST-segment elevation MI.

This usage rate appeared similar in all world regions. The respondents most commonly used the Medtronic 6F Export aspiration catheter, the same device used in the TAPAS study. Of respondents, 80% said that they had the suction turned on before crossing the lesion, and 83% left it on as they withdrew the catheter.

In addition, 20% of the respondents said that they had at least one significant complication when using the device, “an important issue,” Dr. Jolly said.

The most common specific complication cited was thrombus pulled back into the left main coronary artery, reported by 5% of respondents.

Finally, 89% of respondents said that they thought a large randomized trial should assess the safety and efficacy of aspiration thrombectomy in this setting, and 85% expressed a willingness to randomize their patients.

Even among cardiologists who said that they already routinely used thrombectomy for treating patients with an acute myocardial infarction, a similar, large majority voiced their preference for running the trial, Dr. Jolly said.

'Interventional cardiologists feel that a definitive randomized, controlled trial is needed.'

Source DR. JOLLY

Major Finding: Survey results showed that 36% of responding interventional cardiologists routinely use aspiration thrombectomy when treating patients with an acute ST-segment elevation myocardial infarction.

Data Source: Internet-based survey with responses from 477 interventional cardiologists worldwide.

Disclosures: TOTAL is using the Export catheter, which is marketed by Medtronic. Medtronic is cofunding this trial along with the Canadian Network and Centre for Trials Internationally. Dr. Jolly said that he has received grant support from Medtronic, and has received speakers' honoraria from GlaxoSmithKline, Sanofi-Aventis, and Boehringer Ingelheim.

CHICAGO – Most interventional cardiologists remain wary of using thrombus aspiration as initial treatment for an acute myocardial infarction, despite the striking mortality benefit reported for this approach in a single-center study more than 2 years ago.

“Interventional cardiologists feel that a definitive randomized, controlled trial is needed,” according to results from an Internet-based survey with responses from 477 interventionalists, Dr. Sanjit S. Jolly said at the meeting.

Based in part on the equipoise the survey revealed among interventionalists between aspiration thrombectomy followed by percutaneous coronary intervention (PCI), and PCI alone, for treating an acute myocardial infarction, Dr. Jolly said that he and his associates began TOTAL, a multicenter Trial of Routine Aspiration Thrombectomy With Percutaneous Coronary Intervention versus PCI Alone in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary PCI.

The researchers designed TOTAL to randomize 4,000 patients, said Dr. Jolly, a cardiologist at McMaster University in Hamilton, Ont. He said they hope to have the study completed within the next 2 years.

Aspiration thrombectomy as initial treatment for an acute ST-segment elevation myocardial infarction burst onto the scene in June 2008 with the publication of results from the Thrombus Aspiration During Percutaneous Coronary Intervention in Acute Myocardial Infarction Study (TAPAS), which involved 1,071 patients treated at the University Medical Center Groningen (the Netherlands).

In that study, at 1 year after treatment, the rate of cardiac death reached 3.6% in the patients randomized to thrombectomy plus PCI and 6.7% in those treated by standard PCI alone. The difference was statistically significant (Lancet 2008;371:1915-20).

This “unexpected” substantial advantage in favor of thrombectomy “created a lot of press,” Dr. Jolly commented.

However, a subsequent meta-analysis of thrombectomy for treating acute myocardial infarctions that included 21 studies (including the results from TAPAS) with a total of nearly 4,300 patients failed to find that adding thrombectomy led to a significant improvement in survival compared with primary PCI alone (Circ. Cardiovasc. Interv. 2010;3:6-16).

To get a better sense of the worldwide use of thrombectomy, Dr. Jolly and his associates distributed their survey to 1,651 interventionalists worldwide and received 477 responses. The results showed that 36% of respondents reported using thrombectomy routinely along with PCI when treating patients with an acute ST-segment elevation MI.

This usage rate appeared similar in all world regions. The respondents most commonly used the Medtronic 6F Export aspiration catheter, the same device used in the TAPAS study. Of respondents, 80% said that they had the suction turned on before crossing the lesion, and 83% left it on as they withdrew the catheter.

In addition, 20% of the respondents said that they had at least one significant complication when using the device, “an important issue,” Dr. Jolly said.

The most common specific complication cited was thrombus pulled back into the left main coronary artery, reported by 5% of respondents.

Finally, 89% of respondents said that they thought a large randomized trial should assess the safety and efficacy of aspiration thrombectomy in this setting, and 85% expressed a willingness to randomize their patients.

Even among cardiologists who said that they already routinely used thrombectomy for treating patients with an acute myocardial infarction, a similar, large majority voiced their preference for running the trial, Dr. Jolly said.

'Interventional cardiologists feel that a definitive randomized, controlled trial is needed.'

Source DR. JOLLY

Major Finding: Survey results showed that 36% of responding interventional cardiologists routinely use aspiration thrombectomy when treating patients with an acute ST-segment elevation myocardial infarction.

Data Source: Internet-based survey with responses from 477 interventional cardiologists worldwide.

Disclosures: TOTAL is using the Export catheter, which is marketed by Medtronic. Medtronic is cofunding this trial along with the Canadian Network and Centre for Trials Internationally. Dr. Jolly said that he has received grant support from Medtronic, and has received speakers' honoraria from GlaxoSmithKline, Sanofi-Aventis, and Boehringer Ingelheim.

CHICAGO – Most interventional cardiologists remain wary of using thrombus aspiration as initial treatment for an acute myocardial infarction, despite the striking mortality benefit reported for this approach in a single-center study more than 2 years ago.

“Interventional cardiologists feel that a definitive randomized, controlled trial is needed,” according to results from an Internet-based survey with responses from 477 interventionalists, Dr. Sanjit S. Jolly said at the meeting.

Based in part on the equipoise the survey revealed among interventionalists between aspiration thrombectomy followed by percutaneous coronary intervention (PCI), and PCI alone, for treating an acute myocardial infarction, Dr. Jolly said that he and his associates began TOTAL, a multicenter Trial of Routine Aspiration Thrombectomy With Percutaneous Coronary Intervention versus PCI Alone in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary PCI.

The researchers designed TOTAL to randomize 4,000 patients, said Dr. Jolly, a cardiologist at McMaster University in Hamilton, Ont. He said they hope to have the study completed within the next 2 years.

Aspiration thrombectomy as initial treatment for an acute ST-segment elevation myocardial infarction burst onto the scene in June 2008 with the publication of results from the Thrombus Aspiration During Percutaneous Coronary Intervention in Acute Myocardial Infarction Study (TAPAS), which involved 1,071 patients treated at the University Medical Center Groningen (the Netherlands).

In that study, at 1 year after treatment, the rate of cardiac death reached 3.6% in the patients randomized to thrombectomy plus PCI and 6.7% in those treated by standard PCI alone. The difference was statistically significant (Lancet 2008;371:1915-20).

This “unexpected” substantial advantage in favor of thrombectomy “created a lot of press,” Dr. Jolly commented.

However, a subsequent meta-analysis of thrombectomy for treating acute myocardial infarctions that included 21 studies (including the results from TAPAS) with a total of nearly 4,300 patients failed to find that adding thrombectomy led to a significant improvement in survival compared with primary PCI alone (Circ. Cardiovasc. Interv. 2010;3:6-16).

To get a better sense of the worldwide use of thrombectomy, Dr. Jolly and his associates distributed their survey to 1,651 interventionalists worldwide and received 477 responses. The results showed that 36% of respondents reported using thrombectomy routinely along with PCI when treating patients with an acute ST-segment elevation MI.

This usage rate appeared similar in all world regions. The respondents most commonly used the Medtronic 6F Export aspiration catheter, the same device used in the TAPAS study. Of respondents, 80% said that they had the suction turned on before crossing the lesion, and 83% left it on as they withdrew the catheter.

In addition, 20% of the respondents said that they had at least one significant complication when using the device, “an important issue,” Dr. Jolly said.

The most common specific complication cited was thrombus pulled back into the left main coronary artery, reported by 5% of respondents.

Finally, 89% of respondents said that they thought a large randomized trial should assess the safety and efficacy of aspiration thrombectomy in this setting, and 85% expressed a willingness to randomize their patients.

Even among cardiologists who said that they already routinely used thrombectomy for treating patients with an acute myocardial infarction, a similar, large majority voiced their preference for running the trial, Dr. Jolly said.

'Interventional cardiologists feel that a definitive randomized, controlled trial is needed.'

Source DR. JOLLY

Major Finding: In a series of patients with large-vessel strokes who failed conventional treatment, deployment of either a Wingspan or Enterprise stent resulted in TIMI grade 2 or 3 blood flow in 95% of treated patients. At 90 days after treatment, 42% of patients had a modified Rankin score of 2 or less.

Data Source: Single-center series of 19 patients with large-vessel strokes who failed initial treatment with a combination of intra-arterial tissue plasminogen activator and attempted clot removal using either the Merci or Penumbra devices.

Disclosures: Dr. Linfante said that he has served as a speaker for or as a consultant to Codman (the company that markets the Enterprise stent), Micrus Endovascular, and Surpass Medical.

MIAMI BEACH – Deployed stents produced unexpectedly good outcomes in a series of 19 stroke patients with large-vessel occlusions that resisted recanalization by more conventional treatments.

“Stenting is a safe and very effective option,” Dr. Italo Linfante said at the meeting. In the series of 19 patients he reported, 8 (42%) had a modified Rankin score of 2 (slight disability) or less at 90 days after stent placement after failing recanalization with intra-arterial tissue plasminogen activator (tPA) as well as treatment with either the Merci clot retriever or the Penumbra clot suction device.

Without stent treatment as a last resort, expected mortality in the series would have been about 90%, said Dr. Linfante, director of interventional neuroradiology at the Baptist Cardiac & Vascular Institute in Miami Beach. This series included five deaths – a 26.3% mortality.

“These are desperate cases.” When clot lysis or removal fails “there is nothing else to do” but try stent deployment or stent placement and retrieval, Dr. Linfante said in an interview. For patients with large-vessel occlusions, “we usually try one or two passes with a device,” either Merci or Penumbra, but this fails in about 40% of patients, who then immediately become candidates for stenting.

Stenting was also relatively safe, with no device-related complications. The five deaths comprised three patients who died from hemorrhagic transformations and two who died from large ischemic infarctions. Dr. Linfante attributed the hemorrhages to delayed recanalization rather than to any stenting-related problems.

“Some patients had huge strokes. You can open their arteries beautifully, but it's too late because by the time you have tried everything else and then go to a stent you're already 2 hours into the procedure. Then when you open the artery it's either too late or the patient bleeds,” he said.

Selected patients with large-vessel strokes are likely good candidates for immediate stenting, an approach that would avoid delaying treatment with failed attempts to remove the clot, he added. But currently, no evidence-based method exists for identifying which stroke patients with large-vessel occlusions are likely to fail conventional clot-removal treatments.

In Dr. Linfante's experience, clot removal typically fails in patients with occlusions that also involve a substantial amount of plaque. As experience with acute stroke stenting grows and more reports appear in the literature it will become easier to skip an attempt at clot removal in such patients and proceed directly to stenting, he said.

Dr. Linfante treated the 19 patients in his series during August 2008–September 2010. They ranged in age from 28 to 91 years, with an average age of 65 years. Their average NIH stroke scale score was 18, with one patient having a score as high as 28. All had complete obstructions with no blood flow in their affected vessel. Ten patients had obstructions at the M1 level of the middle cerebral artery; in four, the block occurred at the terminus of the internal carotid, three had occlusions of their basilar artery, and two had tandem occlusions in both the middle and internal carotid arteries.

Despite the time needed for the initial, failed attempts at clot removal, 14 patients underwent stenting within 8 hours of symptom onset. Thirteen patients received a Wingspan stent (Boston Scientific), the only stent with approval from the Food and Drug Administration for use in stroke occlusions, Dr. Linfante said. In six patients, vessel tortuosity prevented deployment of a Wingspan stent and so he used an Enterprise stent (Codman).

In 13 patients (68%), stenting resulted in TIMI 3-level blood flow through the affected vessel, and in another five patients it produced TIMI 2 flow. In the final patient from the series stenting led to TIMI 1 flow. In addition to the eight patients who had a modified Rankin score of 2 or less 90 days after treatment, another four patients had a modified Rankin score of 3 (moderate disability) at follow-up.

'These are desperate cases.' When clot lysis or removal fails, there is nothing left to do but try a stent.

Source DR. LINFANTE

Major Finding: In a series of patients with large-vessel strokes who failed conventional treatment, deployment of either a Wingspan or Enterprise stent resulted in TIMI grade 2 or 3 blood flow in 95% of treated patients. At 90 days after treatment, 42% of patients had a modified Rankin score of 2 or less.

Data Source: Single-center series of 19 patients with large-vessel strokes who failed initial treatment with a combination of intra-arterial tissue plasminogen activator and attempted clot removal using either the Merci or Penumbra devices.

Disclosures: Dr. Linfante said that he has served as a speaker for or as a consultant to Codman (the company that markets the Enterprise stent), Micrus Endovascular, and Surpass Medical.

MIAMI BEACH – Deployed stents produced unexpectedly good outcomes in a series of 19 stroke patients with large-vessel occlusions that resisted recanalization by more conventional treatments.

“Stenting is a safe and very effective option,” Dr. Italo Linfante said at the meeting. In the series of 19 patients he reported, 8 (42%) had a modified Rankin score of 2 (slight disability) or less at 90 days after stent placement after failing recanalization with intra-arterial tissue plasminogen activator (tPA) as well as treatment with either the Merci clot retriever or the Penumbra clot suction device.

Without stent treatment as a last resort, expected mortality in the series would have been about 90%, said Dr. Linfante, director of interventional neuroradiology at the Baptist Cardiac & Vascular Institute in Miami Beach. This series included five deaths – a 26.3% mortality.

“These are desperate cases.” When clot lysis or removal fails “there is nothing else to do” but try stent deployment or stent placement and retrieval, Dr. Linfante said in an interview. For patients with large-vessel occlusions, “we usually try one or two passes with a device,” either Merci or Penumbra, but this fails in about 40% of patients, who then immediately become candidates for stenting.

Stenting was also relatively safe, with no device-related complications. The five deaths comprised three patients who died from hemorrhagic transformations and two who died from large ischemic infarctions. Dr. Linfante attributed the hemorrhages to delayed recanalization rather than to any stenting-related problems.

“Some patients had huge strokes. You can open their arteries beautifully, but it's too late because by the time you have tried everything else and then go to a stent you're already 2 hours into the procedure. Then when you open the artery it's either too late or the patient bleeds,” he said.

Selected patients with large-vessel strokes are likely good candidates for immediate stenting, an approach that would avoid delaying treatment with failed attempts to remove the clot, he added. But currently, no evidence-based method exists for identifying which stroke patients with large-vessel occlusions are likely to fail conventional clot-removal treatments.

In Dr. Linfante's experience, clot removal typically fails in patients with occlusions that also involve a substantial amount of plaque. As experience with acute stroke stenting grows and more reports appear in the literature it will become easier to skip an attempt at clot removal in such patients and proceed directly to stenting, he said.

Dr. Linfante treated the 19 patients in his series during August 2008–September 2010. They ranged in age from 28 to 91 years, with an average age of 65 years. Their average NIH stroke scale score was 18, with one patient having a score as high as 28. All had complete obstructions with no blood flow in their affected vessel. Ten patients had obstructions at the M1 level of the middle cerebral artery; in four, the block occurred at the terminus of the internal carotid, three had occlusions of their basilar artery, and two had tandem occlusions in both the middle and internal carotid arteries.

Despite the time needed for the initial, failed attempts at clot removal, 14 patients underwent stenting within 8 hours of symptom onset. Thirteen patients received a Wingspan stent (Boston Scientific), the only stent with approval from the Food and Drug Administration for use in stroke occlusions, Dr. Linfante said. In six patients, vessel tortuosity prevented deployment of a Wingspan stent and so he used an Enterprise stent (Codman).

In 13 patients (68%), stenting resulted in TIMI 3-level blood flow through the affected vessel, and in another five patients it produced TIMI 2 flow. In the final patient from the series stenting led to TIMI 1 flow. In addition to the eight patients who had a modified Rankin score of 2 or less 90 days after treatment, another four patients had a modified Rankin score of 3 (moderate disability) at follow-up.

'These are desperate cases.' When clot lysis or removal fails, there is nothing left to do but try a stent.

Source DR. LINFANTE

Major Finding: In a series of patients with large-vessel strokes who failed conventional treatment, deployment of either a Wingspan or Enterprise stent resulted in TIMI grade 2 or 3 blood flow in 95% of treated patients. At 90 days after treatment, 42% of patients had a modified Rankin score of 2 or less.

Data Source: Single-center series of 19 patients with large-vessel strokes who failed initial treatment with a combination of intra-arterial tissue plasminogen activator and attempted clot removal using either the Merci or Penumbra devices.

Disclosures: Dr. Linfante said that he has served as a speaker for or as a consultant to Codman (the company that markets the Enterprise stent), Micrus Endovascular, and Surpass Medical.

MIAMI BEACH – Deployed stents produced unexpectedly good outcomes in a series of 19 stroke patients with large-vessel occlusions that resisted recanalization by more conventional treatments.

“Stenting is a safe and very effective option,” Dr. Italo Linfante said at the meeting. In the series of 19 patients he reported, 8 (42%) had a modified Rankin score of 2 (slight disability) or less at 90 days after stent placement after failing recanalization with intra-arterial tissue plasminogen activator (tPA) as well as treatment with either the Merci clot retriever or the Penumbra clot suction device.

Without stent treatment as a last resort, expected mortality in the series would have been about 90%, said Dr. Linfante, director of interventional neuroradiology at the Baptist Cardiac & Vascular Institute in Miami Beach. This series included five deaths – a 26.3% mortality.

“These are desperate cases.” When clot lysis or removal fails “there is nothing else to do” but try stent deployment or stent placement and retrieval, Dr. Linfante said in an interview. For patients with large-vessel occlusions, “we usually try one or two passes with a device,” either Merci or Penumbra, but this fails in about 40% of patients, who then immediately become candidates for stenting.

Stenting was also relatively safe, with no device-related complications. The five deaths comprised three patients who died from hemorrhagic transformations and two who died from large ischemic infarctions. Dr. Linfante attributed the hemorrhages to delayed recanalization rather than to any stenting-related problems.

“Some patients had huge strokes. You can open their arteries beautifully, but it's too late because by the time you have tried everything else and then go to a stent you're already 2 hours into the procedure. Then when you open the artery it's either too late or the patient bleeds,” he said.

Selected patients with large-vessel strokes are likely good candidates for immediate stenting, an approach that would avoid delaying treatment with failed attempts to remove the clot, he added. But currently, no evidence-based method exists for identifying which stroke patients with large-vessel occlusions are likely to fail conventional clot-removal treatments.

In Dr. Linfante's experience, clot removal typically fails in patients with occlusions that also involve a substantial amount of plaque. As experience with acute stroke stenting grows and more reports appear in the literature it will become easier to skip an attempt at clot removal in such patients and proceed directly to stenting, he said.

Dr. Linfante treated the 19 patients in his series during August 2008–September 2010. They ranged in age from 28 to 91 years, with an average age of 65 years. Their average NIH stroke scale score was 18, with one patient having a score as high as 28. All had complete obstructions with no blood flow in their affected vessel. Ten patients had obstructions at the M1 level of the middle cerebral artery; in four, the block occurred at the terminus of the internal carotid, three had occlusions of their basilar artery, and two had tandem occlusions in both the middle and internal carotid arteries.

Despite the time needed for the initial, failed attempts at clot removal, 14 patients underwent stenting within 8 hours of symptom onset. Thirteen patients received a Wingspan stent (Boston Scientific), the only stent with approval from the Food and Drug Administration for use in stroke occlusions, Dr. Linfante said. In six patients, vessel tortuosity prevented deployment of a Wingspan stent and so he used an Enterprise stent (Codman).

In 13 patients (68%), stenting resulted in TIMI 3-level blood flow through the affected vessel, and in another five patients it produced TIMI 2 flow. In the final patient from the series stenting led to TIMI 1 flow. In addition to the eight patients who had a modified Rankin score of 2 or less 90 days after treatment, another four patients had a modified Rankin score of 3 (moderate disability) at follow-up.

'These are desperate cases.' When clot lysis or removal fails, there is nothing left to do but try a stent.

Source DR. LINFANTE

Major Finding: In patients who received a cardiac resynchronization device to treat severe heart failure, three different methods for setting the atrioventricular delay – an echocardiographic assessment, a built-in program of the device, and a fixed, 120-msec delay used for all patients – produced no statistically significant differences in the change in left ventricular end systolic volume at 6 months after device placement.

Data Source: The SMART-AV trial, which randomized and implanted 980 patients at 100 centers in the United States and Europe during May 2008–December 2009.

Disclosures: The study was sponsored by Boston Scientific. Dr. Ellenbogen said that he has served as a consultant or an advisory board member to, lectured on behalf of, and/or received research grants from, Boston Scientific, Biotronik, Medtronic, St. Jude Medical, Sorin Group, Cardionet, Atricare, EBR, Sanofi-Aventis, and Biosense Webster. Dr. Tomaselli said that he had no disclosures.

CHICAGO – The standard, atrioventricular delay built into many cardiac resynchronization devices worked as effectively as did an automated patient-tailored delay or a delay based on a time-consuming echocardiography assessment in a randomized trial that involved nearly 1,000 patients.

“The routine use of AV [atrioventricular] optimization techniques assessed in this trial is not warranted,” Dr. Kenneth A. Ellenbogen said at the meeting. But it may help patients who don't initially respond to cardiac resynchronization therapy (CRT), he added, although the results he reported did not assess this possibility.

The findings refuted a recommendation made in 2008 by a panel of the American Society of Echocardiography to routinely use an echo assessment to set the AV delay in patients receiving a CRT device (J. Am. Soc. Echocardiogr. 2008;21:191-213).

“The algorithms [for determining an optimal AV delay] made excellent sense hemodynamically, but you need a clinical trial to look at clinical outcomes,” said Dr. Ellenbogen, vice-chairman of cardiology and director of clinical cardiac electrophysiology and pacing at Virginia Commonwealth University in Richmond, Va.

“The bottom line is we can save patients an expensive and time-consuming study that really doesn't benefit the majority of patients. The out-of-the-box settings seem to work in most patients,” he added.

A detailed echo study “is about an hour long and uses resources,” and was no better than the alternatives, commented Dr. Gordon F. Tomaselli, professor and chief of cardiology at Johns Hopkins University in Baltimore. “The key comparison of the study was do we need to do a detailed echo study on everyone to optimize the hemodynamics, and the answer was no,” he said in an interview.

The results also called into question the usefulness of a feature in all CRT devices on the U.S. market that automatically attempts to optimize the AV delay based on what the device detects as the patient's intrinsic AV interval and baseline QRS width. In the Boston Scientific CRT unit used in the new study, this feature is called “SmartDelay.” The study results showed no stagnificant benefit from the SmartDelay feature compared with a fixed AV delay of 120 msec for all patients.

“All the companies have their algorithms” for setting the AV delay, said Dr. Tomaselli. He also noted that while the new results showed no significant difference between the fixed delay of 120 msec and the variable delays applied by the device's built-in programming function, several outcomes showed trends toward superiority using the built-in program.

For example, in the study's primary outcome – the median change in left ventricular end systolic volume at 6 months after placement of the CRT device – the results showed a median 21-mL reduction in patients whose delay got set by the device's internal program (which produced an average delay of 48 msec) and a median 15-mL reduction in patients who received a device set to the fixed, 120-msec delay. Patients who underwent an echo-guided procedure to set the delay had a median reduction of 19 mL.

The SmartDelay Determined AV Optimization: A Comparison to Other AV Delay Methods Used in Cardiac Resynchronization Therapy (SMART-AV) trial randomized and implanted 980 patients at 100 centers in the United States and Europe during May 2008–December 2009. The researchers were able to perform follow-up assessments on 86% of the randomized patients. The patients' average age was 66, two-thirds were men, and more than 90% had New York Heart Association class III heart failure.

The study's secondary outcomes analyses also showed no significant differences between the three methods used to set the AV delay for changes in left ventricular end diastolic volume, ejection fraction, 6-minute walk, quality of life, or NYHA heart failure class. A series of post hoc subgroup analyses also generally showed no differenceinetween the three methods. These included patients with ischemic or nonischemic heart failure etiology, patients with either greater or less than 30% atrial pacing, patients with or without bundle branch block, and those with a QRS duration of less than 150 msec and those with a duration of at least 150 msec.

The only subgroup that showed a differential effect was in women, who had a significantly better response to either the device-selected AV delay or an echo-guided delay compared with the fixed, 120-msec delay. In men, the three approaches had identical effects. The implications of this finding for selecting a CRT delay in women will need further study, Dr. Ellenbogen said. He also stressed the need to compare the efficacy of the three delay-setting approaches in the roughly 25% of patients who don't initially respond to their CRT device.

Concurrently with Dr. Ellenbogen's report at the meeting, the results were published online (Circulation 2010 Nov. 15 [doi:10.1161/circulationaha.110.992552]).

Major Finding: In patients who received a cardiac resynchronization device to treat severe heart failure, three different methods for setting the atrioventricular delay – an echocardiographic assessment, a built-in program of the device, and a fixed, 120-msec delay used for all patients – produced no statistically significant differences in the change in left ventricular end systolic volume at 6 months after device placement.

Data Source: The SMART-AV trial, which randomized and implanted 980 patients at 100 centers in the United States and Europe during May 2008–December 2009.

Disclosures: The study was sponsored by Boston Scientific. Dr. Ellenbogen said that he has served as a consultant or an advisory board member to, lectured on behalf of, and/or received research grants from, Boston Scientific, Biotronik, Medtronic, St. Jude Medical, Sorin Group, Cardionet, Atricare, EBR, Sanofi-Aventis, and Biosense Webster. Dr. Tomaselli said that he had no disclosures.

CHICAGO – The standard, atrioventricular delay built into many cardiac resynchronization devices worked as effectively as did an automated patient-tailored delay or a delay based on a time-consuming echocardiography assessment in a randomized trial that involved nearly 1,000 patients.

“The routine use of AV [atrioventricular] optimization techniques assessed in this trial is not warranted,” Dr. Kenneth A. Ellenbogen said at the meeting. But it may help patients who don't initially respond to cardiac resynchronization therapy (CRT), he added, although the results he reported did not assess this possibility.

The findings refuted a recommendation made in 2008 by a panel of the American Society of Echocardiography to routinely use an echo assessment to set the AV delay in patients receiving a CRT device (J. Am. Soc. Echocardiogr. 2008;21:191-213).

“The algorithms [for determining an optimal AV delay] made excellent sense hemodynamically, but you need a clinical trial to look at clinical outcomes,” said Dr. Ellenbogen, vice-chairman of cardiology and director of clinical cardiac electrophysiology and pacing at Virginia Commonwealth University in Richmond, Va.

“The bottom line is we can save patients an expensive and time-consuming study that really doesn't benefit the majority of patients. The out-of-the-box settings seem to work in most patients,” he added.

A detailed echo study “is about an hour long and uses resources,” and was no better than the alternatives, commented Dr. Gordon F. Tomaselli, professor and chief of cardiology at Johns Hopkins University in Baltimore. “The key comparison of the study was do we need to do a detailed echo study on everyone to optimize the hemodynamics, and the answer was no,” he said in an interview.

The results also called into question the usefulness of a feature in all CRT devices on the U.S. market that automatically attempts to optimize the AV delay based on what the device detects as the patient's intrinsic AV interval and baseline QRS width. In the Boston Scientific CRT unit used in the new study, this feature is called “SmartDelay.” The study results showed no stagnificant benefit from the SmartDelay feature compared with a fixed AV delay of 120 msec for all patients.

“All the companies have their algorithms” for setting the AV delay, said Dr. Tomaselli. He also noted that while the new results showed no significant difference between the fixed delay of 120 msec and the variable delays applied by the device's built-in programming function, several outcomes showed trends toward superiority using the built-in program.

For example, in the study's primary outcome – the median change in left ventricular end systolic volume at 6 months after placement of the CRT device – the results showed a median 21-mL reduction in patients whose delay got set by the device's internal program (which produced an average delay of 48 msec) and a median 15-mL reduction in patients who received a device set to the fixed, 120-msec delay. Patients who underwent an echo-guided procedure to set the delay had a median reduction of 19 mL.

The SmartDelay Determined AV Optimization: A Comparison to Other AV Delay Methods Used in Cardiac Resynchronization Therapy (SMART-AV) trial randomized and implanted 980 patients at 100 centers in the United States and Europe during May 2008–December 2009. The researchers were able to perform follow-up assessments on 86% of the randomized patients. The patients' average age was 66, two-thirds were men, and more than 90% had New York Heart Association class III heart failure.

The study's secondary outcomes analyses also showed no significant differences between the three methods used to set the AV delay for changes in left ventricular end diastolic volume, ejection fraction, 6-minute walk, quality of life, or NYHA heart failure class. A series of post hoc subgroup analyses also generally showed no differenceinetween the three methods. These included patients with ischemic or nonischemic heart failure etiology, patients with either greater or less than 30% atrial pacing, patients with or without bundle branch block, and those with a QRS duration of less than 150 msec and those with a duration of at least 150 msec.

The only subgroup that showed a differential effect was in women, who had a significantly better response to either the device-selected AV delay or an echo-guided delay compared with the fixed, 120-msec delay. In men, the three approaches had identical effects. The implications of this finding for selecting a CRT delay in women will need further study, Dr. Ellenbogen said. He also stressed the need to compare the efficacy of the three delay-setting approaches in the roughly 25% of patients who don't initially respond to their CRT device.

Concurrently with Dr. Ellenbogen's report at the meeting, the results were published online (Circulation 2010 Nov. 15 [doi:10.1161/circulationaha.110.992552]).

Major Finding: In patients who received a cardiac resynchronization device to treat severe heart failure, three different methods for setting the atrioventricular delay – an echocardiographic assessment, a built-in program of the device, and a fixed, 120-msec delay used for all patients – produced no statistically significant differences in the change in left ventricular end systolic volume at 6 months after device placement.

Data Source: The SMART-AV trial, which randomized and implanted 980 patients at 100 centers in the United States and Europe during May 2008–December 2009.

Disclosures: The study was sponsored by Boston Scientific. Dr. Ellenbogen said that he has served as a consultant or an advisory board member to, lectured on behalf of, and/or received research grants from, Boston Scientific, Biotronik, Medtronic, St. Jude Medical, Sorin Group, Cardionet, Atricare, EBR, Sanofi-Aventis, and Biosense Webster. Dr. Tomaselli said that he had no disclosures.

CHICAGO – The standard, atrioventricular delay built into many cardiac resynchronization devices worked as effectively as did an automated patient-tailored delay or a delay based on a time-consuming echocardiography assessment in a randomized trial that involved nearly 1,000 patients.

“The routine use of AV [atrioventricular] optimization techniques assessed in this trial is not warranted,” Dr. Kenneth A. Ellenbogen said at the meeting. But it may help patients who don't initially respond to cardiac resynchronization therapy (CRT), he added, although the results he reported did not assess this possibility.

The findings refuted a recommendation made in 2008 by a panel of the American Society of Echocardiography to routinely use an echo assessment to set the AV delay in patients receiving a CRT device (J. Am. Soc. Echocardiogr. 2008;21:191-213).

“The algorithms [for determining an optimal AV delay] made excellent sense hemodynamically, but you need a clinical trial to look at clinical outcomes,” said Dr. Ellenbogen, vice-chairman of cardiology and director of clinical cardiac electrophysiology and pacing at Virginia Commonwealth University in Richmond, Va.

“The bottom line is we can save patients an expensive and time-consuming study that really doesn't benefit the majority of patients. The out-of-the-box settings seem to work in most patients,” he added.

A detailed echo study “is about an hour long and uses resources,” and was no better than the alternatives, commented Dr. Gordon F. Tomaselli, professor and chief of cardiology at Johns Hopkins University in Baltimore. “The key comparison of the study was do we need to do a detailed echo study on everyone to optimize the hemodynamics, and the answer was no,” he said in an interview.

The results also called into question the usefulness of a feature in all CRT devices on the U.S. market that automatically attempts to optimize the AV delay based on what the device detects as the patient's intrinsic AV interval and baseline QRS width. In the Boston Scientific CRT unit used in the new study, this feature is called “SmartDelay.” The study results showed no stagnificant benefit from the SmartDelay feature compared with a fixed AV delay of 120 msec for all patients.

“All the companies have their algorithms” for setting the AV delay, said Dr. Tomaselli. He also noted that while the new results showed no significant difference between the fixed delay of 120 msec and the variable delays applied by the device's built-in programming function, several outcomes showed trends toward superiority using the built-in program.

For example, in the study's primary outcome – the median change in left ventricular end systolic volume at 6 months after placement of the CRT device – the results showed a median 21-mL reduction in patients whose delay got set by the device's internal program (which produced an average delay of 48 msec) and a median 15-mL reduction in patients who received a device set to the fixed, 120-msec delay. Patients who underwent an echo-guided procedure to set the delay had a median reduction of 19 mL.

The SmartDelay Determined AV Optimization: A Comparison to Other AV Delay Methods Used in Cardiac Resynchronization Therapy (SMART-AV) trial randomized and implanted 980 patients at 100 centers in the United States and Europe during May 2008–December 2009. The researchers were able to perform follow-up assessments on 86% of the randomized patients. The patients' average age was 66, two-thirds were men, and more than 90% had New York Heart Association class III heart failure.

The study's secondary outcomes analyses also showed no significant differences between the three methods used to set the AV delay for changes in left ventricular end diastolic volume, ejection fraction, 6-minute walk, quality of life, or NYHA heart failure class. A series of post hoc subgroup analyses also generally showed no differenceinetween the three methods. These included patients with ischemic or nonischemic heart failure etiology, patients with either greater or less than 30% atrial pacing, patients with or without bundle branch block, and those with a QRS duration of less than 150 msec and those with a duration of at least 150 msec.

The only subgroup that showed a differential effect was in women, who had a significantly better response to either the device-selected AV delay or an echo-guided delay compared with the fixed, 120-msec delay. In men, the three approaches had identical effects. The implications of this finding for selecting a CRT delay in women will need further study, Dr. Ellenbogen said. He also stressed the need to compare the efficacy of the three delay-setting approaches in the roughly 25% of patients who don't initially respond to their CRT device.

Concurrently with Dr. Ellenbogen's report at the meeting, the results were published online (Circulation 2010 Nov. 15 [doi:10.1161/circulationaha.110.992552]).

Major Finding: Among women with diabetes who had the haptoglobin 2-2 genotype, every-other-day supplementation with 600 IU of vitamin E led to a 15% reduction in all cardiovascular events during 10 years of follow-up and a 4.5-fold reduction in stroke compared with similar women who were randomized to placebo.

Data Source: Post hoc analysis of 1,027 women with diabetes who were enrolled in the Women's Health Study.

Disclosures: Dr. Blum said he had no disclosures. Dr Levy has served as a consultant for Synvista Therapeutics. Dr. Brinton said that he has served as a consultant to, or as a speaker for, Abbott, Amarin, AstraZeneca, Atherotech, Bristol-Myers Squibb, Daiichi-Sankyo, GlaxoSmithKline, Kaneka, Kowa, Kronos Longevity Research Institute, Merck, and Takeda. He has received research grants from Abbott, the Aurora Foundation, and GlaxoSmithKline, and has been an expert witness for the law firm of Reilly Pozner.

CHICAGO – Evidence continues to build that vitamin E, an antioxidant supplement that became discredited and discarded for preventing cardiovascular disease events through the accumulated results from several large, negative trials, may actually have a substantial benefit for a select subgroup of patients with diabetes.

The key appears to be targeting vitamin E to patients with diabetes who also have a haptoglobin 2-2 genotype, which means they lack a robust antioxidant effect from this blood protein. Roughly a third of people in Western populations carry this genotype. Everyone else has a 1-1 or 2-1 genotype, both of which produce haptoglobin with adequate antioxidant activity.

The latest results to back up this paradigm came from a post hoc analysis of the 1,027 women with diabetes enrolled in the Women's Health Study (WHS). In this analysis, women with diabetes and the haptoglobin 2-2 genotype who received an every-other-day supplement of 600 IU of vitamin E had a 15% reduced rate of cardiovascular disease events during an average 10 years of follow-up compared with similar women randomized to placebo, Dr. Shany Blum said at the meeting.

In contrast, post hoc analysis of WHS women with diabetes and the 2-1 genotype who received vitamin E showed a 20%-25% increased rate of cardiovascular disease events during follow-up compared with similar women who received placebo.

The stroke rate in women with the 2-1 haptoglobin genotype was 5.7% in those who received vitamin E and 1.2% in the placebo arm, a 4.5-fold increased rate of stroke after adjustment, said Dr. Blum, a researcher at the Technion-Israel Institute of Technology in Haifa.

These findings follow similar observations about the interaction of vitamin E and the haptoglobin genotype in both women and men with diabetes in a post hoc analysis of data from the Heart Outcomes Prevention Evaluation (HOPE) study (N. Engl. J. Med. 2000;342:154-60), and from a prospective test of vitamin E compared with placebo in 1,434 patients with diabetes and the haptoglobin 2-2 genotype in the Israel Cardiovascular Events Reduction With Vitamin E (ICARE) study (Arterioscler. Thromb. Vasc. Biol. 2008;28:341-7).

Both studies used a daily supplement with 400 IU of vitamin E. The Haifa researchers published a meta-analysis of the results from HOPE and ICARE in patients with diabetes analyzed by their haptoglobin genotype last May (Pharmacogenomics 2010;11:675-84).

“We have now addressed, in three independent studies, the ability to target specifically haptoglobin 2-2 individuals with antioxidant treatment, particularly vitamin E,” said Dr. Andrew P. Levy, professor of anatomy and cell biology at the Technion-Israel Institute and the lead investigator of these analyses and the ICARE study.

“We've now shown in the HOPE study, ICARE, and WHS that patients with the 2-2 genotype [and diabetes] benefited from receiving vitamin E. In HOPE, they had about a 30% reduction in cardiovascular events [compared with patients who received placebo], in ICARE about a 45% reduction in cardiovascular events, and in the WHS about a 15% reduction in cardiovascular events,” Dr. Levy said in an interview.

The HOPE and WHS studies “had previously both shown no overall benefit from vitamin E” compared with placebo when the analysis included all participants, regardless of their diabetes status and haptoglobin genotype status. “But when we specifically targeted people with 2-2, they benefited from vitamin E treatment,” he said.

Dr. Levy stressed that in his opinion this paradigm needs additional testing in a large, prospective trial before physicians start routinely prescribing vitamin E to patients with diabetes and a haptoglobin 2-2 genotype. He conceded, however, that such a study may be difficult to fund, as no drug company stands to reap a financial benefit from vitamin E, an inexpensive generic agent.

At least one expert familiar with this work believes the evidence that Dr. Levy and his associates have collected warrants starting vitamin E supplementation immediately in informed and willing patients who have the right risk profile.

A daily dose of 400 IU of vitamin E is “cheap and innocuous,” commented Dr. Eliot A. Brinton, director of the metabolism section in the cardiovascular genetics division at the University of Utah, Salt Lake City. “The question that I would pose to my patients with diabetes is 'Do you want this?' Many of my patients would probably say yes, they do.”

Women with diabetes and the 2-1 genotype who received vitamin E showed a 20%-25% increased rate of CV events.

Source DR. BLUM

Major Finding: Among women with diabetes who had the haptoglobin 2-2 genotype, every-other-day supplementation with 600 IU of vitamin E led to a 15% reduction in all cardiovascular events during 10 years of follow-up and a 4.5-fold reduction in stroke compared with similar women who were randomized to placebo.

Data Source: Post hoc analysis of 1,027 women with diabetes who were enrolled in the Women's Health Study.

Disclosures: Dr. Blum said he had no disclosures. Dr Levy has served as a consultant for Synvista Therapeutics. Dr. Brinton said that he has served as a consultant to, or as a speaker for, Abbott, Amarin, AstraZeneca, Atherotech, Bristol-Myers Squibb, Daiichi-Sankyo, GlaxoSmithKline, Kaneka, Kowa, Kronos Longevity Research Institute, Merck, and Takeda. He has received research grants from Abbott, the Aurora Foundation, and GlaxoSmithKline, and has been an expert witness for the law firm of Reilly Pozner.

CHICAGO – Evidence continues to build that vitamin E, an antioxidant supplement that became discredited and discarded for preventing cardiovascular disease events through the accumulated results from several large, negative trials, may actually have a substantial benefit for a select subgroup of patients with diabetes.

The key appears to be targeting vitamin E to patients with diabetes who also have a haptoglobin 2-2 genotype, which means they lack a robust antioxidant effect from this blood protein. Roughly a third of people in Western populations carry this genotype. Everyone else has a 1-1 or 2-1 genotype, both of which produce haptoglobin with adequate antioxidant activity.

The latest results to back up this paradigm came from a post hoc analysis of the 1,027 women with diabetes enrolled in the Women's Health Study (WHS). In this analysis, women with diabetes and the haptoglobin 2-2 genotype who received an every-other-day supplement of 600 IU of vitamin E had a 15% reduced rate of cardiovascular disease events during an average 10 years of follow-up compared with similar women randomized to placebo, Dr. Shany Blum said at the meeting.

In contrast, post hoc analysis of WHS women with diabetes and the 2-1 genotype who received vitamin E showed a 20%-25% increased rate of cardiovascular disease events during follow-up compared with similar women who received placebo.

The stroke rate in women with the 2-1 haptoglobin genotype was 5.7% in those who received vitamin E and 1.2% in the placebo arm, a 4.5-fold increased rate of stroke after adjustment, said Dr. Blum, a researcher at the Technion-Israel Institute of Technology in Haifa.

These findings follow similar observations about the interaction of vitamin E and the haptoglobin genotype in both women and men with diabetes in a post hoc analysis of data from the Heart Outcomes Prevention Evaluation (HOPE) study (N. Engl. J. Med. 2000;342:154-60), and from a prospective test of vitamin E compared with placebo in 1,434 patients with diabetes and the haptoglobin 2-2 genotype in the Israel Cardiovascular Events Reduction With Vitamin E (ICARE) study (Arterioscler. Thromb. Vasc. Biol. 2008;28:341-7).

Both studies used a daily supplement with 400 IU of vitamin E. The Haifa researchers published a meta-analysis of the results from HOPE and ICARE in patients with diabetes analyzed by their haptoglobin genotype last May (Pharmacogenomics 2010;11:675-84).

“We have now addressed, in three independent studies, the ability to target specifically haptoglobin 2-2 individuals with antioxidant treatment, particularly vitamin E,” said Dr. Andrew P. Levy, professor of anatomy and cell biology at the Technion-Israel Institute and the lead investigator of these analyses and the ICARE study.

“We've now shown in the HOPE study, ICARE, and WHS that patients with the 2-2 genotype [and diabetes] benefited from receiving vitamin E. In HOPE, they had about a 30% reduction in cardiovascular events [compared with patients who received placebo], in ICARE about a 45% reduction in cardiovascular events, and in the WHS about a 15% reduction in cardiovascular events,” Dr. Levy said in an interview.

The HOPE and WHS studies “had previously both shown no overall benefit from vitamin E” compared with placebo when the analysis included all participants, regardless of their diabetes status and haptoglobin genotype status. “But when we specifically targeted people with 2-2, they benefited from vitamin E treatment,” he said.

Dr. Levy stressed that in his opinion this paradigm needs additional testing in a large, prospective trial before physicians start routinely prescribing vitamin E to patients with diabetes and a haptoglobin 2-2 genotype. He conceded, however, that such a study may be difficult to fund, as no drug company stands to reap a financial benefit from vitamin E, an inexpensive generic agent.

At least one expert familiar with this work believes the evidence that Dr. Levy and his associates have collected warrants starting vitamin E supplementation immediately in informed and willing patients who have the right risk profile.

A daily dose of 400 IU of vitamin E is “cheap and innocuous,” commented Dr. Eliot A. Brinton, director of the metabolism section in the cardiovascular genetics division at the University of Utah, Salt Lake City. “The question that I would pose to my patients with diabetes is 'Do you want this?' Many of my patients would probably say yes, they do.”

Women with diabetes and the 2-1 genotype who received vitamin E showed a 20%-25% increased rate of CV events.

Source DR. BLUM

Major Finding: Among women with diabetes who had the haptoglobin 2-2 genotype, every-other-day supplementation with 600 IU of vitamin E led to a 15% reduction in all cardiovascular events during 10 years of follow-up and a 4.5-fold reduction in stroke compared with similar women who were randomized to placebo.

Data Source: Post hoc analysis of 1,027 women with diabetes who were enrolled in the Women's Health Study.

Disclosures: Dr. Blum said he had no disclosures. Dr Levy has served as a consultant for Synvista Therapeutics. Dr. Brinton said that he has served as a consultant to, or as a speaker for, Abbott, Amarin, AstraZeneca, Atherotech, Bristol-Myers Squibb, Daiichi-Sankyo, GlaxoSmithKline, Kaneka, Kowa, Kronos Longevity Research Institute, Merck, and Takeda. He has received research grants from Abbott, the Aurora Foundation, and GlaxoSmithKline, and has been an expert witness for the law firm of Reilly Pozner.

CHICAGO – Evidence continues to build that vitamin E, an antioxidant supplement that became discredited and discarded for preventing cardiovascular disease events through the accumulated results from several large, negative trials, may actually have a substantial benefit for a select subgroup of patients with diabetes.

The key appears to be targeting vitamin E to patients with diabetes who also have a haptoglobin 2-2 genotype, which means they lack a robust antioxidant effect from this blood protein. Roughly a third of people in Western populations carry this genotype. Everyone else has a 1-1 or 2-1 genotype, both of which produce haptoglobin with adequate antioxidant activity.

The latest results to back up this paradigm came from a post hoc analysis of the 1,027 women with diabetes enrolled in the Women's Health Study (WHS). In this analysis, women with diabetes and the haptoglobin 2-2 genotype who received an every-other-day supplement of 600 IU of vitamin E had a 15% reduced rate of cardiovascular disease events during an average 10 years of follow-up compared with similar women randomized to placebo, Dr. Shany Blum said at the meeting.

In contrast, post hoc analysis of WHS women with diabetes and the 2-1 genotype who received vitamin E showed a 20%-25% increased rate of cardiovascular disease events during follow-up compared with similar women who received placebo.

The stroke rate in women with the 2-1 haptoglobin genotype was 5.7% in those who received vitamin E and 1.2% in the placebo arm, a 4.5-fold increased rate of stroke after adjustment, said Dr. Blum, a researcher at the Technion-Israel Institute of Technology in Haifa.

These findings follow similar observations about the interaction of vitamin E and the haptoglobin genotype in both women and men with diabetes in a post hoc analysis of data from the Heart Outcomes Prevention Evaluation (HOPE) study (N. Engl. J. Med. 2000;342:154-60), and from a prospective test of vitamin E compared with placebo in 1,434 patients with diabetes and the haptoglobin 2-2 genotype in the Israel Cardiovascular Events Reduction With Vitamin E (ICARE) study (Arterioscler. Thromb. Vasc. Biol. 2008;28:341-7).

Both studies used a daily supplement with 400 IU of vitamin E. The Haifa researchers published a meta-analysis of the results from HOPE and ICARE in patients with diabetes analyzed by their haptoglobin genotype last May (Pharmacogenomics 2010;11:675-84).

“We have now addressed, in three independent studies, the ability to target specifically haptoglobin 2-2 individuals with antioxidant treatment, particularly vitamin E,” said Dr. Andrew P. Levy, professor of anatomy and cell biology at the Technion-Israel Institute and the lead investigator of these analyses and the ICARE study.

“We've now shown in the HOPE study, ICARE, and WHS that patients with the 2-2 genotype [and diabetes] benefited from receiving vitamin E. In HOPE, they had about a 30% reduction in cardiovascular events [compared with patients who received placebo], in ICARE about a 45% reduction in cardiovascular events, and in the WHS about a 15% reduction in cardiovascular events,” Dr. Levy said in an interview.

The HOPE and WHS studies “had previously both shown no overall benefit from vitamin E” compared with placebo when the analysis included all participants, regardless of their diabetes status and haptoglobin genotype status. “But when we specifically targeted people with 2-2, they benefited from vitamin E treatment,” he said.

Dr. Levy stressed that in his opinion this paradigm needs additional testing in a large, prospective trial before physicians start routinely prescribing vitamin E to patients with diabetes and a haptoglobin 2-2 genotype. He conceded, however, that such a study may be difficult to fund, as no drug company stands to reap a financial benefit from vitamin E, an inexpensive generic agent.

At least one expert familiar with this work believes the evidence that Dr. Levy and his associates have collected warrants starting vitamin E supplementation immediately in informed and willing patients who have the right risk profile.

A daily dose of 400 IU of vitamin E is “cheap and innocuous,” commented Dr. Eliot A. Brinton, director of the metabolism section in the cardiovascular genetics division at the University of Utah, Salt Lake City. “The question that I would pose to my patients with diabetes is 'Do you want this?' Many of my patients would probably say yes, they do.”

Women with diabetes and the 2-1 genotype who received vitamin E showed a 20%-25% increased rate of CV events.

Source DR. BLUM

Major Finding: A 3-month program of intensive knee rehabilitation produced a significant, 30% improvement in knee extension and flexion in patients with articular cartilage lesions who were scheduled for repair surgery. After the program ended, 64% of participants said they no longer needed immediate surgery.

Data Source: Single-center study of 48 patients with articular cartilage lesions.

Disclosures: Dr. Risberg said she had no conflicts of interest.

BRUSSELS – A carefully designed, 3-month program of rehabilitation exercise and education in patients with articular cartilage lesions who were scheduled for cartilage repair surgery led to significant improvements in knee function in a single-center study with 48 patients.

Following the 3-month rehabilitation intervention, 64% of the patients said they no longer needed immediate surgery, said May Arna Risberg, Ph.D.

“I believe this [rehabilitation] program works for these patients. We will publish the program, and continue to use it ourselves, and we hope others will use it,” said Dr. Risberg, professor of sports medicine at the Norwegian School of Sport Sciences in Oslo. Gradually increasing knee loading using an individualized schedule may explain the rehab program's success, she said.

“Patients with cartilage lesions are very different from osteoarthritis patients. You need to go much slower with progression of their knee loading. Rehab for cartilage needs to be slow and long,” she said in an interview.

All 48 patients in the study had undergone prior rehab sessions run by other clinicians, but aside from the focus on a gradual pace, an emphasis on using knee loading to guide the program's intensity, and a strong education component, the rehab program tested by Dr. Risberg didn't involve any novel approaches or exercise regimens.

Participating patients attended rehab sessions of the Oslo CARE (cartilage, active, rehab, and education) program an average of twice a week. Sessions included warm-up stretches, gait retraining, neuromuscular exercises, step-up and step-down exercises, and strength exercise for knee and hip muscles. Both the step and strength exercises featured gradually increasing loading over time. The program also included educational sessions and materials.

The study enrolled patients who had a focal femoral-condyle defect in the articular cartilage of one knee, diagnosed by arthroscopy, and who were scheduled for repair surgery. Their age averaged 34 years (range, 17-50); 70% were men, and 84% had a medial femoral-condyle lesion. Participants had had their symptoms for an average of 47 months prior to the study.

Analysis of training diaries and responses in biweekly questionnaires showed that 79% of participants adhered to their rehab regimens, and 88% had follow-up assessments an average of 104 days after they entered the study.

At follow-up, participants averaged a 30% improvement over baseline in both extension and flexion of their injured knee, Dr. Risberg reported at the meeting, sponsored by the Osteoarthritis Research Society International. They also averaged improvements of 21%, 31%, and 37% in the triple, crossover, and one-leg hop tests, respectively, compared with baseline, all statistically significant increases.

They also had significant improvements in measures of pain, activity, and quality of life. Dr. Risberg cited the finding that nearly two-thirds of patients said they no longer needed immediate knee surgery as the best demonstration of their improvement.

She cautioned that despite completing the 3-month program, some patients had no significant response to their rehabilitation, and that additional studies should test the program in more patients with longer follow-up.

Major Finding: A 3-month program of intensive knee rehabilitation produced a significant, 30% improvement in knee extension and flexion in patients with articular cartilage lesions who were scheduled for repair surgery. After the program ended, 64% of participants said they no longer needed immediate surgery.

Data Source: Single-center study of 48 patients with articular cartilage lesions.

Disclosures: Dr. Risberg said she had no conflicts of interest.

BRUSSELS – A carefully designed, 3-month program of rehabilitation exercise and education in patients with articular cartilage lesions who were scheduled for cartilage repair surgery led to significant improvements in knee function in a single-center study with 48 patients.

Following the 3-month rehabilitation intervention, 64% of the patients said they no longer needed immediate surgery, said May Arna Risberg, Ph.D.

“I believe this [rehabilitation] program works for these patients. We will publish the program, and continue to use it ourselves, and we hope others will use it,” said Dr. Risberg, professor of sports medicine at the Norwegian School of Sport Sciences in Oslo. Gradually increasing knee loading using an individualized schedule may explain the rehab program's success, she said.

“Patients with cartilage lesions are very different from osteoarthritis patients. You need to go much slower with progression of their knee loading. Rehab for cartilage needs to be slow and long,” she said in an interview.

All 48 patients in the study had undergone prior rehab sessions run by other clinicians, but aside from the focus on a gradual pace, an emphasis on using knee loading to guide the program's intensity, and a strong education component, the rehab program tested by Dr. Risberg didn't involve any novel approaches or exercise regimens.

Participating patients attended rehab sessions of the Oslo CARE (cartilage, active, rehab, and education) program an average of twice a week. Sessions included warm-up stretches, gait retraining, neuromuscular exercises, step-up and step-down exercises, and strength exercise for knee and hip muscles. Both the step and strength exercises featured gradually increasing loading over time. The program also included educational sessions and materials.

The study enrolled patients who had a focal femoral-condyle defect in the articular cartilage of one knee, diagnosed by arthroscopy, and who were scheduled for repair surgery. Their age averaged 34 years (range, 17-50); 70% were men, and 84% had a medial femoral-condyle lesion. Participants had had their symptoms for an average of 47 months prior to the study.

Analysis of training diaries and responses in biweekly questionnaires showed that 79% of participants adhered to their rehab regimens, and 88% had follow-up assessments an average of 104 days after they entered the study.

At follow-up, participants averaged a 30% improvement over baseline in both extension and flexion of their injured knee, Dr. Risberg reported at the meeting, sponsored by the Osteoarthritis Research Society International. They also averaged improvements of 21%, 31%, and 37% in the triple, crossover, and one-leg hop tests, respectively, compared with baseline, all statistically significant increases.

They also had significant improvements in measures of pain, activity, and quality of life. Dr. Risberg cited the finding that nearly two-thirds of patients said they no longer needed immediate knee surgery as the best demonstration of their improvement.

She cautioned that despite completing the 3-month program, some patients had no significant response to their rehabilitation, and that additional studies should test the program in more patients with longer follow-up.

Major Finding: A 3-month program of intensive knee rehabilitation produced a significant, 30% improvement in knee extension and flexion in patients with articular cartilage lesions who were scheduled for repair surgery. After the program ended, 64% of participants said they no longer needed immediate surgery.

Data Source: Single-center study of 48 patients with articular cartilage lesions.

Disclosures: Dr. Risberg said she had no conflicts of interest.

BRUSSELS – A carefully designed, 3-month program of rehabilitation exercise and education in patients with articular cartilage lesions who were scheduled for cartilage repair surgery led to significant improvements in knee function in a single-center study with 48 patients.

Following the 3-month rehabilitation intervention, 64% of the patients said they no longer needed immediate surgery, said May Arna Risberg, Ph.D.

“I believe this [rehabilitation] program works for these patients. We will publish the program, and continue to use it ourselves, and we hope others will use it,” said Dr. Risberg, professor of sports medicine at the Norwegian School of Sport Sciences in Oslo. Gradually increasing knee loading using an individualized schedule may explain the rehab program's success, she said.

“Patients with cartilage lesions are very different from osteoarthritis patients. You need to go much slower with progression of their knee loading. Rehab for cartilage needs to be slow and long,” she said in an interview.

All 48 patients in the study had undergone prior rehab sessions run by other clinicians, but aside from the focus on a gradual pace, an emphasis on using knee loading to guide the program's intensity, and a strong education component, the rehab program tested by Dr. Risberg didn't involve any novel approaches or exercise regimens.

Participating patients attended rehab sessions of the Oslo CARE (cartilage, active, rehab, and education) program an average of twice a week. Sessions included warm-up stretches, gait retraining, neuromuscular exercises, step-up and step-down exercises, and strength exercise for knee and hip muscles. Both the step and strength exercises featured gradually increasing loading over time. The program also included educational sessions and materials.

The study enrolled patients who had a focal femoral-condyle defect in the articular cartilage of one knee, diagnosed by arthroscopy, and who were scheduled for repair surgery. Their age averaged 34 years (range, 17-50); 70% were men, and 84% had a medial femoral-condyle lesion. Participants had had their symptoms for an average of 47 months prior to the study.

Analysis of training diaries and responses in biweekly questionnaires showed that 79% of participants adhered to their rehab regimens, and 88% had follow-up assessments an average of 104 days after they entered the study.

At follow-up, participants averaged a 30% improvement over baseline in both extension and flexion of their injured knee, Dr. Risberg reported at the meeting, sponsored by the Osteoarthritis Research Society International. They also averaged improvements of 21%, 31%, and 37% in the triple, crossover, and one-leg hop tests, respectively, compared with baseline, all statistically significant increases.

They also had significant improvements in measures of pain, activity, and quality of life. Dr. Risberg cited the finding that nearly two-thirds of patients said they no longer needed immediate knee surgery as the best demonstration of their improvement.

She cautioned that despite completing the 3-month program, some patients had no significant response to their rehabilitation, and that additional studies should test the program in more patients with longer follow-up.

NEW YORK – Children born to mothers with gestational diabetes during pregnancy had a significantly increased risk of developing attention-deficit/hyperactivity disorder when they reached 6 years old, based on a study with 216 children.

The risk was even greater in children of families with low socioeconomic status. The combined effect of gestational diabetes and low socioeconomic status was linked with a statistically significant, ninefold increased rate of attention-deficit/hyperactivity disorder (ADHD) in children when they reached age 6 years, Alexandra S. Jordan reported in a poster at the annual meeting of the American Academy of Child & Adolescent Psychiatry.

The findings "raise the possibility that manifestations of ADHD are not simply genetically mediated. Rather, susceptibility may increase as a function of the uterine environment (as with gestational diabetes) and may be further aggravated as a result of socioeconomic hardship during childhood," Ms. Jordan and her associates reported in their poster.

Prior, published reports had identified both gestational diabetes and low socioeconomic status as risk factors for the subsequent development of ADHD in young children. But in this study, when the researchers looked at the impact of both factors together, "something bizarre happened." The risk increased "way beyond the expected impact," Ms. Jordan said in an interview. She and her colleagues do not currently have an explanation for this apparent synergistic interaction.

The study assessed 216 unselected children for ADHD symptoms at age 4 years and for a diagnosis of ADHD at age 6 years. The mothers of 21 of the children had gestational diabetes during pregnancy, and this subgroup had a 2.19-fold increased risk for having a diagnosis of ADHD at age 6 years, compared with the children born to mothers who never had gestational diabetes. In addition, 104 of the children came from low socioeconomic status households, and these children had a 2.05-fold increased rate of having ADHD, compared with the other children from higher socioeconomic families, said Ms. Jordan, a researcher in the department of counseling and clinical psychology at Columbia University in New York.

The group included nine children whose mother had gestational diabetes and who came from low socioeconomic family. In this subgroup, the prevalence of the ADHD diagnosis at age 6 years was 9.23-fold higher than it was for the children whose mothers did not have gestational diabetes and who came from families with higher socioeconomic status.

The apparent effect of gestational diabetes and low socioeconomic status on ADHD prevalence remained statistically significant after researchers adjusted for whether one or both parents had ADHD.

"These findings may be useful in educating women considering pregnancy, particularly those in low socioeconomic environments, about the potential lingering effects of gestational diabetes on offspring into childhood," the researchers said in their poster. "This information may encourage women to control gestational diabetes symptoms during pregnancy." In addition, it may help "educate health care providers on the importance of assessment and control of gestational diabetes symptoms throughout pregnancy and on ADHD’s etiologic link to gestational diabetes." The findings might also help "target early interventions to those low socioeconomic status families who are most vulnerable" to this interaction with gestational diabetes, they said.

Ms. Jordan had no relevant financial disclosures.

NEW YORK – Children born to mothers with gestational diabetes during pregnancy had a significantly increased risk of developing attention-deficit/hyperactivity disorder when they reached 6 years old, based on a study with 216 children.

The risk was even greater in children of families with low socioeconomic status. The combined effect of gestational diabetes and low socioeconomic status was linked with a statistically significant, ninefold increased rate of attention-deficit/hyperactivity disorder (ADHD) in children when they reached age 6 years, Alexandra S. Jordan reported in a poster at the annual meeting of the American Academy of Child & Adolescent Psychiatry.

The findings "raise the possibility that manifestations of ADHD are not simply genetically mediated. Rather, susceptibility may increase as a function of the uterine environment (as with gestational diabetes) and may be further aggravated as a result of socioeconomic hardship during childhood," Ms. Jordan and her associates reported in their poster.

Prior, published reports had identified both gestational diabetes and low socioeconomic status as risk factors for the subsequent development of ADHD in young children. But in this study, when the researchers looked at the impact of both factors together, "something bizarre happened." The risk increased "way beyond the expected impact," Ms. Jordan said in an interview. She and her colleagues do not currently have an explanation for this apparent synergistic interaction.

The study assessed 216 unselected children for ADHD symptoms at age 4 years and for a diagnosis of ADHD at age 6 years. The mothers of 21 of the children had gestational diabetes during pregnancy, and this subgroup had a 2.19-fold increased risk for having a diagnosis of ADHD at age 6 years, compared with the children born to mothers who never had gestational diabetes. In addition, 104 of the children came from low socioeconomic status households, and these children had a 2.05-fold increased rate of having ADHD, compared with the other children from higher socioeconomic families, said Ms. Jordan, a researcher in the department of counseling and clinical psychology at Columbia University in New York.

The group included nine children whose mother had gestational diabetes and who came from low socioeconomic family. In this subgroup, the prevalence of the ADHD diagnosis at age 6 years was 9.23-fold higher than it was for the children whose mothers did not have gestational diabetes and who came from families with higher socioeconomic status.

The apparent effect of gestational diabetes and low socioeconomic status on ADHD prevalence remained statistically significant after researchers adjusted for whether one or both parents had ADHD.

"These findings may be useful in educating women considering pregnancy, particularly those in low socioeconomic environments, about the potential lingering effects of gestational diabetes on offspring into childhood," the researchers said in their poster. "This information may encourage women to control gestational diabetes symptoms during pregnancy." In addition, it may help "educate health care providers on the importance of assessment and control of gestational diabetes symptoms throughout pregnancy and on ADHD’s etiologic link to gestational diabetes." The findings might also help "target early interventions to those low socioeconomic status families who are most vulnerable" to this interaction with gestational diabetes, they said.

Ms. Jordan had no relevant financial disclosures.

NEW YORK – Children born to mothers with gestational diabetes during pregnancy had a significantly increased risk of developing attention-deficit/hyperactivity disorder when they reached 6 years old, based on a study with 216 children.

The risk was even greater in children of families with low socioeconomic status. The combined effect of gestational diabetes and low socioeconomic status was linked with a statistically significant, ninefold increased rate of attention-deficit/hyperactivity disorder (ADHD) in children when they reached age 6 years, Alexandra S. Jordan reported in a poster at the annual meeting of the American Academy of Child & Adolescent Psychiatry.

The findings "raise the possibility that manifestations of ADHD are not simply genetically mediated. Rather, susceptibility may increase as a function of the uterine environment (as with gestational diabetes) and may be further aggravated as a result of socioeconomic hardship during childhood," Ms. Jordan and her associates reported in their poster.

Prior, published reports had identified both gestational diabetes and low socioeconomic status as risk factors for the subsequent development of ADHD in young children. But in this study, when the researchers looked at the impact of both factors together, "something bizarre happened." The risk increased "way beyond the expected impact," Ms. Jordan said in an interview. She and her colleagues do not currently have an explanation for this apparent synergistic interaction.

The study assessed 216 unselected children for ADHD symptoms at age 4 years and for a diagnosis of ADHD at age 6 years. The mothers of 21 of the children had gestational diabetes during pregnancy, and this subgroup had a 2.19-fold increased risk for having a diagnosis of ADHD at age 6 years, compared with the children born to mothers who never had gestational diabetes. In addition, 104 of the children came from low socioeconomic status households, and these children had a 2.05-fold increased rate of having ADHD, compared with the other children from higher socioeconomic families, said Ms. Jordan, a researcher in the department of counseling and clinical psychology at Columbia University in New York.

The group included nine children whose mother had gestational diabetes and who came from low socioeconomic family. In this subgroup, the prevalence of the ADHD diagnosis at age 6 years was 9.23-fold higher than it was for the children whose mothers did not have gestational diabetes and who came from families with higher socioeconomic status.

The apparent effect of gestational diabetes and low socioeconomic status on ADHD prevalence remained statistically significant after researchers adjusted for whether one or both parents had ADHD.

"These findings may be useful in educating women considering pregnancy, particularly those in low socioeconomic environments, about the potential lingering effects of gestational diabetes on offspring into childhood," the researchers said in their poster. "This information may encourage women to control gestational diabetes symptoms during pregnancy." In addition, it may help "educate health care providers on the importance of assessment and control of gestational diabetes symptoms throughout pregnancy and on ADHD’s etiologic link to gestational diabetes." The findings might also help "target early interventions to those low socioeconomic status families who are most vulnerable" to this interaction with gestational diabetes, they said.

Ms. Jordan had no relevant financial disclosures.