Michele Sullivan

The investigational antiplatelet drug cangrelor outperformed clopidogrel during percutaneous coronary intervention, significantly reducing the risk of death, myocardial infarction, ischemic events, and stent thrombosis by 22%.

A 20% decrease in heart attack risk accounted for most of the benefit, which was achieved without an increased risk for bleeding. Cangrelor showed some treatment flexibility as well, maintaining its benefits whether given before, during, or after PCI.

The study – CHAMPION PHOENIX – was presented at the annual meeting of the American College of Cardiology and published simultaneously in the New England Journal of Medicine (2013; DOI:10.1056/NEJMoa1300815).

The findings shed a more positive light on cangrelor, which fared poorly in two discontinued phase III trials, CHAMPION-PLATFORM, and CHAMPION-PCI; both studies examined the drug’s use in PCI. In 2009, The Medicines Company, which manufactures cangrelor, pulled the plug on both trials after deciding that neither would provide enough positive evidence to pave the way for approval.

In 2012, however, the company published positive results from its BRIDGE trial, finding that cangrelor could effectively maintain anticoagulation for patients who needed to stop their regular antiplatelet therapy while waiting for a non-emergency coronary artery bypass graft.

While neither of the CHAMPION trials met their primary endpoints, both showed positive findings on some secondary endpoints, including stent thrombosis, according to Dr. Deepak L. Bhatt of the Veterans Administration Boston Healthcare System, and his coauthors.

CHAMPION PHOENIX comprised 11,145 patients undergoing either urgent or elective PCI. They were randomized to either a cangrelor/clopidogrel or clopidogrel-only protocol. Patients in the study arm received a cangrelor bolus and infusion, followed by placebo capsules before PCI, and either 300 mg or 600 mg of clopidogrel after (according to the site investigator’s preference). Patients in the comparator group received a placebo bolus and infusion, followed by clopidogrel before PCI and placebo capsules after.

The primary endpoint was a combination of death, myocardial infarction (MI), revascularization because of ischemia, or stent thrombosis at 48 hours after treatment. The secondary endpoint was stent thrombosis at 48 hours. Severe bleeding at 48 hours was the primary safety endpoint.

The patients’ average age was 64 years. Stable angina was the most common indication for PCI (56%). Other indications were non–ST-segment elevation acute coronary syndrome (26%) and ST-segment elevation MI (18%).

The median time from admission to PCI was just over 4 hours. Drug-eluting stents were placed in 56% of the group and bare-metal stents in 42%.

The combined primary endpoint occurred in 5% of the cangrelor group and 6% of the clopidogrel group – a significant 22% risk reduction. The number needed to treat to prevent 1 primary endpoint event was 84.

Stent thrombosis was also significantly less common in the cangrelor group, compared with the placebo group (0.8% vs. 1.4%; OR 0.62).

At 30 days, the incidence of the composite primary endpoint remained significantly lower in the cangrelor group, compared with the placebo group (6% vs. 7%; OR 0.85), as did the incidence of stent thrombosis (1.3% vs. 1.9%; OR 0.68).

 The rate of intraprocedural stent thrombosis was also significantly lower in the cangrelor group, compared with the placebo group (0.6% vs. 1%; OR 0.65). Rescue therapy was employed in significantly fewer patients taking cangrelor (2.3% vs. 3.5%; OR 0.65). The rate of procedural complications was also significantly lower in patients taking cangrelor (3.4% vs. 4.5%; OR 0.74).

The rate of severe bleeding was 0.16% in the cangrelor group and 0.11% in the clopidogrel group – not significantly different. Overall, the rate of adverse events was similar, occurring in 20% of cangrelor patients, compared with 19% of clopidogrel patients. However, patients taking the study drug experienced significantly more dyspnea (1.2% vs. 0.3%).

Cangrelor was equally effective in all patient subgroups, the investigators noted.

Cangrelor demonstrated some treatment flexibility. The drug was equally effective in preventing the primary composite endpoint when given before PCI (OR 0.80), during PCI (OR 0.79), or after PCI (OR 0.79). It also worked equally as well for the 75% of patients who received the 600-mg clopidogrel loading dose, as it did for the 25% who received the 300-mg loading dose (OR 0.77 and 0.84, respectively).

The study design specified at least 2 hours of cangrelor infusion; the median infusion time was 129 minutes. But the drug was just as effective in those who had less than 129 minutes, as for those who had more (OR 0.85 and 0.72, respectively).

Cangrelor is a fast-acting ADP P2Y₁₂ inhibitor, achieving an immediate antiplatelet effect, which is maintained as long as the drug is infused. However, its half-life is extremely short – just 3-5 minutes after discontinuation; platelet function normalizes within 1 hour. Because of this, the drug could benefit those who need a short-acting anticoagulant, the authors noted.

“For example, in patients waiting to undergo open-heart surgery, cangrelor (at a lower dose than that used in this study) has been shown to result in consistent platelet inhibition without a significant increase in bleeding,” they reported.

The Medicines Company funded the study. Dr. Bhatt reported that he has received grant money from numerous pharmaceutical companies. He has also received remuneration for lectures, manuscripts and manuscript preparation, and that he holds patents and receives royalties; however, he did not provide details about any of these disclosures.

michele.sullivan@elsevier.com

The investigational antiplatelet drug cangrelor outperformed clopidogrel during percutaneous coronary intervention, significantly reducing the risk of death, myocardial infarction, ischemic events, and stent thrombosis by 22%.

A 20% decrease in heart attack risk accounted for most of the benefit, which was achieved without an increased risk for bleeding. Cangrelor showed some treatment flexibility as well, maintaining its benefits whether given before, during, or after PCI.

The study – CHAMPION PHOENIX – was presented at the annual meeting of the American College of Cardiology and published simultaneously in the New England Journal of Medicine (2013; DOI:10.1056/NEJMoa1300815).

The findings shed a more positive light on cangrelor, which fared poorly in two discontinued phase III trials, CHAMPION-PLATFORM, and CHAMPION-PCI; both studies examined the drug’s use in PCI. In 2009, The Medicines Company, which manufactures cangrelor, pulled the plug on both trials after deciding that neither would provide enough positive evidence to pave the way for approval.

In 2012, however, the company published positive results from its BRIDGE trial, finding that cangrelor could effectively maintain anticoagulation for patients who needed to stop their regular antiplatelet therapy while waiting for a non-emergency coronary artery bypass graft.

While neither of the CHAMPION trials met their primary endpoints, both showed positive findings on some secondary endpoints, including stent thrombosis, according to Dr. Deepak L. Bhatt of the Veterans Administration Boston Healthcare System, and his coauthors.

CHAMPION PHOENIX comprised 11,145 patients undergoing either urgent or elective PCI. They were randomized to either a cangrelor/clopidogrel or clopidogrel-only protocol. Patients in the study arm received a cangrelor bolus and infusion, followed by placebo capsules before PCI, and either 300 mg or 600 mg of clopidogrel after (according to the site investigator’s preference). Patients in the comparator group received a placebo bolus and infusion, followed by clopidogrel before PCI and placebo capsules after.

The primary endpoint was a combination of death, myocardial infarction (MI), revascularization because of ischemia, or stent thrombosis at 48 hours after treatment. The secondary endpoint was stent thrombosis at 48 hours. Severe bleeding at 48 hours was the primary safety endpoint.

The patients’ average age was 64 years. Stable angina was the most common indication for PCI (56%). Other indications were non–ST-segment elevation acute coronary syndrome (26%) and ST-segment elevation MI (18%).

The median time from admission to PCI was just over 4 hours. Drug-eluting stents were placed in 56% of the group and bare-metal stents in 42%.

The combined primary endpoint occurred in 5% of the cangrelor group and 6% of the clopidogrel group – a significant 22% risk reduction. The number needed to treat to prevent 1 primary endpoint event was 84.

Stent thrombosis was also significantly less common in the cangrelor group, compared with the placebo group (0.8% vs. 1.4%; OR 0.62).

At 30 days, the incidence of the composite primary endpoint remained significantly lower in the cangrelor group, compared with the placebo group (6% vs. 7%; OR 0.85), as did the incidence of stent thrombosis (1.3% vs. 1.9%; OR 0.68).

 The rate of intraprocedural stent thrombosis was also significantly lower in the cangrelor group, compared with the placebo group (0.6% vs. 1%; OR 0.65). Rescue therapy was employed in significantly fewer patients taking cangrelor (2.3% vs. 3.5%; OR 0.65). The rate of procedural complications was also significantly lower in patients taking cangrelor (3.4% vs. 4.5%; OR 0.74).

The rate of severe bleeding was 0.16% in the cangrelor group and 0.11% in the clopidogrel group – not significantly different. Overall, the rate of adverse events was similar, occurring in 20% of cangrelor patients, compared with 19% of clopidogrel patients. However, patients taking the study drug experienced significantly more dyspnea (1.2% vs. 0.3%).

Cangrelor was equally effective in all patient subgroups, the investigators noted.

Cangrelor demonstrated some treatment flexibility. The drug was equally effective in preventing the primary composite endpoint when given before PCI (OR 0.80), during PCI (OR 0.79), or after PCI (OR 0.79). It also worked equally as well for the 75% of patients who received the 600-mg clopidogrel loading dose, as it did for the 25% who received the 300-mg loading dose (OR 0.77 and 0.84, respectively).

The study design specified at least 2 hours of cangrelor infusion; the median infusion time was 129 minutes. But the drug was just as effective in those who had less than 129 minutes, as for those who had more (OR 0.85 and 0.72, respectively).

Cangrelor is a fast-acting ADP P2Y₁₂ inhibitor, achieving an immediate antiplatelet effect, which is maintained as long as the drug is infused. However, its half-life is extremely short – just 3-5 minutes after discontinuation; platelet function normalizes within 1 hour. Because of this, the drug could benefit those who need a short-acting anticoagulant, the authors noted.

“For example, in patients waiting to undergo open-heart surgery, cangrelor (at a lower dose than that used in this study) has been shown to result in consistent platelet inhibition without a significant increase in bleeding,” they reported.

The Medicines Company funded the study. Dr. Bhatt reported that he has received grant money from numerous pharmaceutical companies. He has also received remuneration for lectures, manuscripts and manuscript preparation, and that he holds patents and receives royalties; however, he did not provide details about any of these disclosures.

michele.sullivan@elsevier.com

The investigational antiplatelet drug cangrelor outperformed clopidogrel during percutaneous coronary intervention, significantly reducing the risk of death, myocardial infarction, ischemic events, and stent thrombosis by 22%.

A 20% decrease in heart attack risk accounted for most of the benefit, which was achieved without an increased risk for bleeding. Cangrelor showed some treatment flexibility as well, maintaining its benefits whether given before, during, or after PCI.

The study – CHAMPION PHOENIX – was presented at the annual meeting of the American College of Cardiology and published simultaneously in the New England Journal of Medicine (2013; DOI:10.1056/NEJMoa1300815).

The findings shed a more positive light on cangrelor, which fared poorly in two discontinued phase III trials, CHAMPION-PLATFORM, and CHAMPION-PCI; both studies examined the drug’s use in PCI. In 2009, The Medicines Company, which manufactures cangrelor, pulled the plug on both trials after deciding that neither would provide enough positive evidence to pave the way for approval.

In 2012, however, the company published positive results from its BRIDGE trial, finding that cangrelor could effectively maintain anticoagulation for patients who needed to stop their regular antiplatelet therapy while waiting for a non-emergency coronary artery bypass graft.

While neither of the CHAMPION trials met their primary endpoints, both showed positive findings on some secondary endpoints, including stent thrombosis, according to Dr. Deepak L. Bhatt of the Veterans Administration Boston Healthcare System, and his coauthors.

CHAMPION PHOENIX comprised 11,145 patients undergoing either urgent or elective PCI. They were randomized to either a cangrelor/clopidogrel or clopidogrel-only protocol. Patients in the study arm received a cangrelor bolus and infusion, followed by placebo capsules before PCI, and either 300 mg or 600 mg of clopidogrel after (according to the site investigator’s preference). Patients in the comparator group received a placebo bolus and infusion, followed by clopidogrel before PCI and placebo capsules after.

The primary endpoint was a combination of death, myocardial infarction (MI), revascularization because of ischemia, or stent thrombosis at 48 hours after treatment. The secondary endpoint was stent thrombosis at 48 hours. Severe bleeding at 48 hours was the primary safety endpoint.

The patients’ average age was 64 years. Stable angina was the most common indication for PCI (56%). Other indications were non–ST-segment elevation acute coronary syndrome (26%) and ST-segment elevation MI (18%).

The median time from admission to PCI was just over 4 hours. Drug-eluting stents were placed in 56% of the group and bare-metal stents in 42%.

The combined primary endpoint occurred in 5% of the cangrelor group and 6% of the clopidogrel group – a significant 22% risk reduction. The number needed to treat to prevent 1 primary endpoint event was 84.

Stent thrombosis was also significantly less common in the cangrelor group, compared with the placebo group (0.8% vs. 1.4%; OR 0.62).

At 30 days, the incidence of the composite primary endpoint remained significantly lower in the cangrelor group, compared with the placebo group (6% vs. 7%; OR 0.85), as did the incidence of stent thrombosis (1.3% vs. 1.9%; OR 0.68).

 The rate of intraprocedural stent thrombosis was also significantly lower in the cangrelor group, compared with the placebo group (0.6% vs. 1%; OR 0.65). Rescue therapy was employed in significantly fewer patients taking cangrelor (2.3% vs. 3.5%; OR 0.65). The rate of procedural complications was also significantly lower in patients taking cangrelor (3.4% vs. 4.5%; OR 0.74).

The rate of severe bleeding was 0.16% in the cangrelor group and 0.11% in the clopidogrel group – not significantly different. Overall, the rate of adverse events was similar, occurring in 20% of cangrelor patients, compared with 19% of clopidogrel patients. However, patients taking the study drug experienced significantly more dyspnea (1.2% vs. 0.3%).

Cangrelor was equally effective in all patient subgroups, the investigators noted.

Cangrelor demonstrated some treatment flexibility. The drug was equally effective in preventing the primary composite endpoint when given before PCI (OR 0.80), during PCI (OR 0.79), or after PCI (OR 0.79). It also worked equally as well for the 75% of patients who received the 600-mg clopidogrel loading dose, as it did for the 25% who received the 300-mg loading dose (OR 0.77 and 0.84, respectively).

The study design specified at least 2 hours of cangrelor infusion; the median infusion time was 129 minutes. But the drug was just as effective in those who had less than 129 minutes, as for those who had more (OR 0.85 and 0.72, respectively).

Cangrelor is a fast-acting ADP P2Y₁₂ inhibitor, achieving an immediate antiplatelet effect, which is maintained as long as the drug is infused. However, its half-life is extremely short – just 3-5 minutes after discontinuation; platelet function normalizes within 1 hour. Because of this, the drug could benefit those who need a short-acting anticoagulant, the authors noted.

“For example, in patients waiting to undergo open-heart surgery, cangrelor (at a lower dose than that used in this study) has been shown to result in consistent platelet inhibition without a significant increase in bleeding,” they reported.

The Medicines Company funded the study. Dr. Bhatt reported that he has received grant money from numerous pharmaceutical companies. He has also received remuneration for lectures, manuscripts and manuscript preparation, and that he holds patents and receives royalties; however, he did not provide details about any of these disclosures.

michele.sullivan@elsevier.com

Both men and women who smoke are three times as likely to die as those who don’t.

Two large population-based studies have come to the same conclusion: Smokers are almost certainly going to die years and years sooner than nonsmokers.

"This analysis showed that a person who had never smoked was about twice as likely as a current smoker to reach 80 years of age," Dr. Prabhat Jha and his associates reported in the Jan. 24 issue of the New England Journal of Medicine (N. Engl. J. Med. 2013:368:341-50). "Among current smokers, survival was shorter by about 11 years for women and by about 12 years for men, as compared with participants who had never smoked."

The report wasn’t all bad news, however. Kicking the habit at any time added years of life, said Dr. Jha of the Center for Global Health Research, Toronto, and his coauthors.

The investigators examined smoking and smoking cessation among 113,752 women and 88,496 men who participated in the U.S. National Health Interview Survey from 1997 to 2004. These data were then correlated to information in the National Death Index up until the end of 2006.

The investigators then calculated the probability of survival in each group from 25 to 79 years of age. The mean follow-up was 7 years, with 10,743 deaths occurring in that age range.

After adjusting for education, alcohol use, and adiposity, men and women who smoked were three times more likely to have died than nonsmokers. The estimated probability of survival to the age of 80 years was 38% among women smokers but 70% for those who had never smoked. For male smokers, the probability of survival to age 80 was 26%, compared with 61% for those who had never smoked.

Both women and men who smoked were significantly more likely than nonsmokers to die in all of the smoking-related conditions examined:

• Lung cancer (hazard ratios of 18 and 15 for women and men, respectively).

• Other cancers (HR, 2 and 2).

• All cancers (HR, 3 and 4).

• Ischemic heart disease (HR, 3.5 and 3).

• Stroke (HR, 3 and 2).

• Other vascular disease (HR, 3 and 2).

• Respiratory disease (HR, 8.5 and 9).

• Other unspecified causes (HR, 2 and 2).

• All medical disorders (HR, 3 and 3).

• Accidents (HR, 4 and 2).

"At 25-79 years of age, about 62% of all deaths among female smokers and 60% of all deaths among male smokers would have been avoided if the rates of death from diseases among smokers had been the same as the rates among those who had never smoked," the authors noted.

Quitting smoking, on the other hand, conferred significant survival benefits, no matter when it occurred. Smokers who quit at age 25-34 years had similar survival to that of never-smokers. "Those who quit smoking gained about 10 years of life, as compared with those who continued to smoke."

Quitting at 35-44 years added 9 years of life, the authors found – not quite as good as those who quit earlier, but still a significant gain. "Smokers who had quit by about 39 years of age still had a 20% excess risk as compared with those who had never smoked. Although this hazard is substantial, it is much smaller than the 200% excess risk among those who continued to smoke."

Smokers who stopped at age 45-54 years gained 6 years of life, and those who quit at age 55-64 years about 4 more years of life. "Even cessation at the age of 45 to 54 years reduced the excess risk of death by about two-thirds," according to Dr. Jha and his coauthors.

While the study concluded that quitting at any age is a good idea, it shouldn’t be construed as a license to smoke longer. "That is not to say, however, that it is safe to smoke until 40 years of age and then stop, for the remaining excess risk of about 20% is substantial; it means that about one in six of these former smokers who dies before the age of 80 years would not have died."

The results are consistent with those of other studies around the world, the investigators said. The implications are staggering, especially for lower-income countries where smoking is more common and quitting less common.

"On the basis of current rates of smoking initiation and cessation, smoking, which killed about 100 million people in the 20th century, will kill about 1 billion in the 21st century."

A second study, also published in the Jan. 24 issue of the New England Journal of Medicine, found, for the first time, that women smokers are dying just as quickly – and from the same conditions – as men who smoke.

"The relative risks of death from lung cancer, chronic obstructive pulmonary disease, ischemic heart disease, any type of stroke, and all causes are now nearly identical for female and male smokers," Dr. Michael Thun and his colleagues wrote (N. Engl. J. Med. 2013:368:351-64). "This finding is new and confirms the prediction that, in relative terms, ‘women who smoke like men die like men.’ "

Dr. Thun, an epidemiologist with the American Cancer Society, and his colleagues drew their three study cohorts from seven national studies and databases. The entire study group comprised 1.32 million women and 899,000 men. Two of the cohorts were considered historical, covering 1959-1988; five were considered contemporary, covering 2000-2010. The participants’ ages by the end of each group’s follow-up period ranged from 50 years to more than 80 years.

For never-smokers, the analysis showed a general overall improvement in mortality between the historical and contemporary cohorts. But smokers did not enjoy this benefit. Between the historical and contemporary cohorts, all-cause mortality was 50% higher in smokers than in nonsmokers.

Again, women were particularly at risk, the investigators noted. "In contrast, there was no temporal decrease in the all-cause death rate among women who were current smokers and there was a 23.6% decrease among men who were current smokers. ... The risk of death from lung cancer among male smokers appears to have stabilized since the 1980s, whereas it continues to increase among female smokers."

Dr. Thun and his associates also found the threefold increase in the risk of death between smokers and never-smokers. Their data determined that at least two-thirds of these deaths were directly associated with smoking, including ischemic heart disease, all other heart disease, stroke, and lung cancer.

A comparison of nonsmokers and smokers within all the time cohorts showed that the highest risks of death for most disorders occurred from 1982 to 1988. Since then, the mortality risks have declined and stabilized but still remain elevated compared with never-smokers. The lung cancer mortality risks were strikingly evident, the authors said: a relative risk of 25 for both men and women.

In contrast to the stabilized rates of other diseases, the mortality risk of chronic obstructive pulmonary disease has continued to increase in smokers. The biggest jump affected smokers older than 55 years and occurred after the 1980s period. The overall COPD mortality risk in the 2000-2010 cohort was more than double that of the 1980s (RR 10 vs. 25.6). The risks were similar for women (RR, 10.3-22.3) and men (RR, 12.5-27.3).

The increase is somewhat of a mystery, the authors said. It can’t be explained by aging, smoking duration, or the improved ability to diagnose COPD. Instead, the finding may be related to changes in the way cigarettes are manufactured.

"For example, the introduction of blended tobacco and genetic selection of tobacco plants lowered the pH of smoke; as a result, inhalation was easier and deeper inhalation was needed for the absorption of protonated nicotine. Other design changes, such as the use of more porous wrapping paper and perforated filters, also diluted the smoke. Deeper inhalation of more dilute smoke increases exposure of the lung parenchyma," they wrote.

Histologic studies have also found a change paralleling these manufacturing differences, the authors noted. The changes "may also have contributed to the shift, beginning in the 1970s, in the histological and topographic features of lung cancers in male smokers, with an increase in the incidence of peripheral adenocarcinomas that largely offset the decrease in squamous-cell and small cell cancers of the central airways. The likely net effect of deeper inhalation on COPD could be wholly detrimental, since COPD results from injury to the lung parenchyma."

Dr. Jha’s study was funded by the Fogarty International Center, the National Institutes of Health, the Canadian Institutes of Health Research, and the Bill and Melinda Gates Foundation. Dr. Thun’s study was funded by the National Institutes of Health and the American Cancer Society. None of the authors of either study had any financial disclosures.

Both men and women who smoke are three times as likely to die as those who don’t.

Two large population-based studies have come to the same conclusion: Smokers are almost certainly going to die years and years sooner than nonsmokers.

"This analysis showed that a person who had never smoked was about twice as likely as a current smoker to reach 80 years of age," Dr. Prabhat Jha and his associates reported in the Jan. 24 issue of the New England Journal of Medicine (N. Engl. J. Med. 2013:368:341-50). "Among current smokers, survival was shorter by about 11 years for women and by about 12 years for men, as compared with participants who had never smoked."

The report wasn’t all bad news, however. Kicking the habit at any time added years of life, said Dr. Jha of the Center for Global Health Research, Toronto, and his coauthors.

The investigators examined smoking and smoking cessation among 113,752 women and 88,496 men who participated in the U.S. National Health Interview Survey from 1997 to 2004. These data were then correlated to information in the National Death Index up until the end of 2006.

The investigators then calculated the probability of survival in each group from 25 to 79 years of age. The mean follow-up was 7 years, with 10,743 deaths occurring in that age range.

After adjusting for education, alcohol use, and adiposity, men and women who smoked were three times more likely to have died than nonsmokers. The estimated probability of survival to the age of 80 years was 38% among women smokers but 70% for those who had never smoked. For male smokers, the probability of survival to age 80 was 26%, compared with 61% for those who had never smoked.

Both women and men who smoked were significantly more likely than nonsmokers to die in all of the smoking-related conditions examined:

• Lung cancer (hazard ratios of 18 and 15 for women and men, respectively).

• Other cancers (HR, 2 and 2).

• All cancers (HR, 3 and 4).

• Ischemic heart disease (HR, 3.5 and 3).

• Stroke (HR, 3 and 2).

• Other vascular disease (HR, 3 and 2).

• Respiratory disease (HR, 8.5 and 9).

• Other unspecified causes (HR, 2 and 2).

• All medical disorders (HR, 3 and 3).

• Accidents (HR, 4 and 2).

"At 25-79 years of age, about 62% of all deaths among female smokers and 60% of all deaths among male smokers would have been avoided if the rates of death from diseases among smokers had been the same as the rates among those who had never smoked," the authors noted.

Quitting smoking, on the other hand, conferred significant survival benefits, no matter when it occurred. Smokers who quit at age 25-34 years had similar survival to that of never-smokers. "Those who quit smoking gained about 10 years of life, as compared with those who continued to smoke."

Quitting at 35-44 years added 9 years of life, the authors found – not quite as good as those who quit earlier, but still a significant gain. "Smokers who had quit by about 39 years of age still had a 20% excess risk as compared with those who had never smoked. Although this hazard is substantial, it is much smaller than the 200% excess risk among those who continued to smoke."

Smokers who stopped at age 45-54 years gained 6 years of life, and those who quit at age 55-64 years about 4 more years of life. "Even cessation at the age of 45 to 54 years reduced the excess risk of death by about two-thirds," according to Dr. Jha and his coauthors.

While the study concluded that quitting at any age is a good idea, it shouldn’t be construed as a license to smoke longer. "That is not to say, however, that it is safe to smoke until 40 years of age and then stop, for the remaining excess risk of about 20% is substantial; it means that about one in six of these former smokers who dies before the age of 80 years would not have died."

The results are consistent with those of other studies around the world, the investigators said. The implications are staggering, especially for lower-income countries where smoking is more common and quitting less common.

"On the basis of current rates of smoking initiation and cessation, smoking, which killed about 100 million people in the 20th century, will kill about 1 billion in the 21st century."

A second study, also published in the Jan. 24 issue of the New England Journal of Medicine, found, for the first time, that women smokers are dying just as quickly – and from the same conditions – as men who smoke.

"The relative risks of death from lung cancer, chronic obstructive pulmonary disease, ischemic heart disease, any type of stroke, and all causes are now nearly identical for female and male smokers," Dr. Michael Thun and his colleagues wrote (N. Engl. J. Med. 2013:368:351-64). "This finding is new and confirms the prediction that, in relative terms, ‘women who smoke like men die like men.’ "

Dr. Thun, an epidemiologist with the American Cancer Society, and his colleagues drew their three study cohorts from seven national studies and databases. The entire study group comprised 1.32 million women and 899,000 men. Two of the cohorts were considered historical, covering 1959-1988; five were considered contemporary, covering 2000-2010. The participants’ ages by the end of each group’s follow-up period ranged from 50 years to more than 80 years.

For never-smokers, the analysis showed a general overall improvement in mortality between the historical and contemporary cohorts. But smokers did not enjoy this benefit. Between the historical and contemporary cohorts, all-cause mortality was 50% higher in smokers than in nonsmokers.

Again, women were particularly at risk, the investigators noted. "In contrast, there was no temporal decrease in the all-cause death rate among women who were current smokers and there was a 23.6% decrease among men who were current smokers. ... The risk of death from lung cancer among male smokers appears to have stabilized since the 1980s, whereas it continues to increase among female smokers."

Dr. Thun and his associates also found the threefold increase in the risk of death between smokers and never-smokers. Their data determined that at least two-thirds of these deaths were directly associated with smoking, including ischemic heart disease, all other heart disease, stroke, and lung cancer.

A comparison of nonsmokers and smokers within all the time cohorts showed that the highest risks of death for most disorders occurred from 1982 to 1988. Since then, the mortality risks have declined and stabilized but still remain elevated compared with never-smokers. The lung cancer mortality risks were strikingly evident, the authors said: a relative risk of 25 for both men and women.

In contrast to the stabilized rates of other diseases, the mortality risk of chronic obstructive pulmonary disease has continued to increase in smokers. The biggest jump affected smokers older than 55 years and occurred after the 1980s period. The overall COPD mortality risk in the 2000-2010 cohort was more than double that of the 1980s (RR 10 vs. 25.6). The risks were similar for women (RR, 10.3-22.3) and men (RR, 12.5-27.3).

The increase is somewhat of a mystery, the authors said. It can’t be explained by aging, smoking duration, or the improved ability to diagnose COPD. Instead, the finding may be related to changes in the way cigarettes are manufactured.

"For example, the introduction of blended tobacco and genetic selection of tobacco plants lowered the pH of smoke; as a result, inhalation was easier and deeper inhalation was needed for the absorption of protonated nicotine. Other design changes, such as the use of more porous wrapping paper and perforated filters, also diluted the smoke. Deeper inhalation of more dilute smoke increases exposure of the lung parenchyma," they wrote.

Histologic studies have also found a change paralleling these manufacturing differences, the authors noted. The changes "may also have contributed to the shift, beginning in the 1970s, in the histological and topographic features of lung cancers in male smokers, with an increase in the incidence of peripheral adenocarcinomas that largely offset the decrease in squamous-cell and small cell cancers of the central airways. The likely net effect of deeper inhalation on COPD could be wholly detrimental, since COPD results from injury to the lung parenchyma."

Dr. Jha’s study was funded by the Fogarty International Center, the National Institutes of Health, the Canadian Institutes of Health Research, and the Bill and Melinda Gates Foundation. Dr. Thun’s study was funded by the National Institutes of Health and the American Cancer Society. None of the authors of either study had any financial disclosures.

Both men and women who smoke are three times as likely to die as those who don’t.

Two large population-based studies have come to the same conclusion: Smokers are almost certainly going to die years and years sooner than nonsmokers.

"This analysis showed that a person who had never smoked was about twice as likely as a current smoker to reach 80 years of age," Dr. Prabhat Jha and his associates reported in the Jan. 24 issue of the New England Journal of Medicine (N. Engl. J. Med. 2013:368:341-50). "Among current smokers, survival was shorter by about 11 years for women and by about 12 years for men, as compared with participants who had never smoked."

The report wasn’t all bad news, however. Kicking the habit at any time added years of life, said Dr. Jha of the Center for Global Health Research, Toronto, and his coauthors.

The investigators examined smoking and smoking cessation among 113,752 women and 88,496 men who participated in the U.S. National Health Interview Survey from 1997 to 2004. These data were then correlated to information in the National Death Index up until the end of 2006.

The investigators then calculated the probability of survival in each group from 25 to 79 years of age. The mean follow-up was 7 years, with 10,743 deaths occurring in that age range.

After adjusting for education, alcohol use, and adiposity, men and women who smoked were three times more likely to have died than nonsmokers. The estimated probability of survival to the age of 80 years was 38% among women smokers but 70% for those who had never smoked. For male smokers, the probability of survival to age 80 was 26%, compared with 61% for those who had never smoked.

Both women and men who smoked were significantly more likely than nonsmokers to die in all of the smoking-related conditions examined:

• Lung cancer (hazard ratios of 18 and 15 for women and men, respectively).

• Other cancers (HR, 2 and 2).

• All cancers (HR, 3 and 4).

• Ischemic heart disease (HR, 3.5 and 3).

• Stroke (HR, 3 and 2).

• Other vascular disease (HR, 3 and 2).

• Respiratory disease (HR, 8.5 and 9).

• Other unspecified causes (HR, 2 and 2).

• All medical disorders (HR, 3 and 3).

• Accidents (HR, 4 and 2).

"At 25-79 years of age, about 62% of all deaths among female smokers and 60% of all deaths among male smokers would have been avoided if the rates of death from diseases among smokers had been the same as the rates among those who had never smoked," the authors noted.

Quitting smoking, on the other hand, conferred significant survival benefits, no matter when it occurred. Smokers who quit at age 25-34 years had similar survival to that of never-smokers. "Those who quit smoking gained about 10 years of life, as compared with those who continued to smoke."

Quitting at 35-44 years added 9 years of life, the authors found – not quite as good as those who quit earlier, but still a significant gain. "Smokers who had quit by about 39 years of age still had a 20% excess risk as compared with those who had never smoked. Although this hazard is substantial, it is much smaller than the 200% excess risk among those who continued to smoke."

Smokers who stopped at age 45-54 years gained 6 years of life, and those who quit at age 55-64 years about 4 more years of life. "Even cessation at the age of 45 to 54 years reduced the excess risk of death by about two-thirds," according to Dr. Jha and his coauthors.

While the study concluded that quitting at any age is a good idea, it shouldn’t be construed as a license to smoke longer. "That is not to say, however, that it is safe to smoke until 40 years of age and then stop, for the remaining excess risk of about 20% is substantial; it means that about one in six of these former smokers who dies before the age of 80 years would not have died."

The results are consistent with those of other studies around the world, the investigators said. The implications are staggering, especially for lower-income countries where smoking is more common and quitting less common.

"On the basis of current rates of smoking initiation and cessation, smoking, which killed about 100 million people in the 20th century, will kill about 1 billion in the 21st century."

A second study, also published in the Jan. 24 issue of the New England Journal of Medicine, found, for the first time, that women smokers are dying just as quickly – and from the same conditions – as men who smoke.

"The relative risks of death from lung cancer, chronic obstructive pulmonary disease, ischemic heart disease, any type of stroke, and all causes are now nearly identical for female and male smokers," Dr. Michael Thun and his colleagues wrote (N. Engl. J. Med. 2013:368:351-64). "This finding is new and confirms the prediction that, in relative terms, ‘women who smoke like men die like men.’ "

Dr. Thun, an epidemiologist with the American Cancer Society, and his colleagues drew their three study cohorts from seven national studies and databases. The entire study group comprised 1.32 million women and 899,000 men. Two of the cohorts were considered historical, covering 1959-1988; five were considered contemporary, covering 2000-2010. The participants’ ages by the end of each group’s follow-up period ranged from 50 years to more than 80 years.

For never-smokers, the analysis showed a general overall improvement in mortality between the historical and contemporary cohorts. But smokers did not enjoy this benefit. Between the historical and contemporary cohorts, all-cause mortality was 50% higher in smokers than in nonsmokers.

Again, women were particularly at risk, the investigators noted. "In contrast, there was no temporal decrease in the all-cause death rate among women who were current smokers and there was a 23.6% decrease among men who were current smokers. ... The risk of death from lung cancer among male smokers appears to have stabilized since the 1980s, whereas it continues to increase among female smokers."

Dr. Thun and his associates also found the threefold increase in the risk of death between smokers and never-smokers. Their data determined that at least two-thirds of these deaths were directly associated with smoking, including ischemic heart disease, all other heart disease, stroke, and lung cancer.

A comparison of nonsmokers and smokers within all the time cohorts showed that the highest risks of death for most disorders occurred from 1982 to 1988. Since then, the mortality risks have declined and stabilized but still remain elevated compared with never-smokers. The lung cancer mortality risks were strikingly evident, the authors said: a relative risk of 25 for both men and women.

In contrast to the stabilized rates of other diseases, the mortality risk of chronic obstructive pulmonary disease has continued to increase in smokers. The biggest jump affected smokers older than 55 years and occurred after the 1980s period. The overall COPD mortality risk in the 2000-2010 cohort was more than double that of the 1980s (RR 10 vs. 25.6). The risks were similar for women (RR, 10.3-22.3) and men (RR, 12.5-27.3).

The increase is somewhat of a mystery, the authors said. It can’t be explained by aging, smoking duration, or the improved ability to diagnose COPD. Instead, the finding may be related to changes in the way cigarettes are manufactured.

"For example, the introduction of blended tobacco and genetic selection of tobacco plants lowered the pH of smoke; as a result, inhalation was easier and deeper inhalation was needed for the absorption of protonated nicotine. Other design changes, such as the use of more porous wrapping paper and perforated filters, also diluted the smoke. Deeper inhalation of more dilute smoke increases exposure of the lung parenchyma," they wrote.

Histologic studies have also found a change paralleling these manufacturing differences, the authors noted. The changes "may also have contributed to the shift, beginning in the 1970s, in the histological and topographic features of lung cancers in male smokers, with an increase in the incidence of peripheral adenocarcinomas that largely offset the decrease in squamous-cell and small cell cancers of the central airways. The likely net effect of deeper inhalation on COPD could be wholly detrimental, since COPD results from injury to the lung parenchyma."

Dr. Jha’s study was funded by the Fogarty International Center, the National Institutes of Health, the Canadian Institutes of Health Research, and the Bill and Melinda Gates Foundation. Dr. Thun’s study was funded by the National Institutes of Health and the American Cancer Society. None of the authors of either study had any financial disclosures.

BERLIN – A duodenal-jejunal liner seemed to improve glycemic control in patients with type 2 diabetes, a small prospective study has determined.

Among 16 patients who had the liner for 1 year, mean hemoglobin A_1c dropped more than 1% without any significant weight loss, Dr. Dimitri Pournaras said at the annual meeting of the European Association for the Study of Diabetes.

"Bypassing the gut seems to have an effect on glucose homeostasis that can’t be fully explained by weight loss," said Dr. Pournaras of Imperial College, London.

The flexible barrier attempts to mimic some of the benefits of gastric bypass without surgery, he said. The sleeve is endoscopically placed in the duodenal bulb and extends about 60 cm through the duodenum and proximal jejunum, preventing any nutrient contact with those regions.

Dr. Pournaras presented data on 16 nonobese patients with type 2 diabetes who had the gastric sleeve in place for 1 year.

At baseline, the patients had a body mass index of 23-36 kg/m² and were 35-65 years of age. The mean duration of disease was 2 years, and HbA_1c at baseline was 7.5%-10.2%. All of the patients were taking metformin; none were taking DPP-4 inhibitors, GLP-1 analogues, or insulin.

Investigators examined patients’ glycemic indicators at baseline and at 1, 12, and 52 weeks after the sleeve was placed. After an overnight fast, patients consumed a 525-calorie liquid meal. Blood was drawn before the meal and at 30, 60, 90, and 120 minutes afterward.

There were no significant changes in weight at any time after the surgery. In fact, Dr. Pounaras said, no patient experienced a change in the amount of food consumed.

HbA_1c was significantly lower at 3 months and stayed low throughout the study. At 52 weeks, the mean HbA_1c was 7.5%, compared with the mean of 8.6% at baseline. More than half of the subjects (62%) reached a level of 7%. Fasting glucose and acute glucose response improved significantly. Insulin sensitivity improved early and that was maintained. Insulin resistance, as measured by both the homeostasis model assessment of insulin resistance (HOMA-IR) and the Matsuda index, improved significantly by the end of the follow-up period. Insulin secretion and insulinogenic index were unchanged, as were C-peptide and fasting insulin, he reported.

Four patients experienced transient nausea and abdominal bloating after the sleeve was placed.

Dr. Pournaras did not say how many were able to come off of their metformin, nor did he mention the sleeve’s effect on any other drugs the patients may have been taking. In response to a question on this, he said that "metformin is a safe drug" that should not be used as the measure of diabetes remission.

The sleeve "opens the door to the possibility that we might one day be able to combine the duodenal-jejunal liner with medications such as GLP-1 agonists and DPP-4 inhibitors," Dr. Pournaras said.

The device is not approved for sale in the United States and is considered investigational. It is approved in Europe, and has pending approval in Australia, to treat patients with type 2 diabetes and/or obesity for 12 months.

GI Dynamics, the manufacturer of the device, sponsored the study. Dr. Pournaras did not present any financial disclosures.

BERLIN – A duodenal-jejunal liner seemed to improve glycemic control in patients with type 2 diabetes, a small prospective study has determined.

Among 16 patients who had the liner for 1 year, mean hemoglobin A_1c dropped more than 1% without any significant weight loss, Dr. Dimitri Pournaras said at the annual meeting of the European Association for the Study of Diabetes.

"Bypassing the gut seems to have an effect on glucose homeostasis that can’t be fully explained by weight loss," said Dr. Pournaras of Imperial College, London.

The flexible barrier attempts to mimic some of the benefits of gastric bypass without surgery, he said. The sleeve is endoscopically placed in the duodenal bulb and extends about 60 cm through the duodenum and proximal jejunum, preventing any nutrient contact with those regions.

Dr. Pournaras presented data on 16 nonobese patients with type 2 diabetes who had the gastric sleeve in place for 1 year.

At baseline, the patients had a body mass index of 23-36 kg/m² and were 35-65 years of age. The mean duration of disease was 2 years, and HbA_1c at baseline was 7.5%-10.2%. All of the patients were taking metformin; none were taking DPP-4 inhibitors, GLP-1 analogues, or insulin.

Investigators examined patients’ glycemic indicators at baseline and at 1, 12, and 52 weeks after the sleeve was placed. After an overnight fast, patients consumed a 525-calorie liquid meal. Blood was drawn before the meal and at 30, 60, 90, and 120 minutes afterward.

There were no significant changes in weight at any time after the surgery. In fact, Dr. Pounaras said, no patient experienced a change in the amount of food consumed.

HbA_1c was significantly lower at 3 months and stayed low throughout the study. At 52 weeks, the mean HbA_1c was 7.5%, compared with the mean of 8.6% at baseline. More than half of the subjects (62%) reached a level of 7%. Fasting glucose and acute glucose response improved significantly. Insulin sensitivity improved early and that was maintained. Insulin resistance, as measured by both the homeostasis model assessment of insulin resistance (HOMA-IR) and the Matsuda index, improved significantly by the end of the follow-up period. Insulin secretion and insulinogenic index were unchanged, as were C-peptide and fasting insulin, he reported.

Four patients experienced transient nausea and abdominal bloating after the sleeve was placed.

Dr. Pournaras did not say how many were able to come off of their metformin, nor did he mention the sleeve’s effect on any other drugs the patients may have been taking. In response to a question on this, he said that "metformin is a safe drug" that should not be used as the measure of diabetes remission.

The sleeve "opens the door to the possibility that we might one day be able to combine the duodenal-jejunal liner with medications such as GLP-1 agonists and DPP-4 inhibitors," Dr. Pournaras said.

The device is not approved for sale in the United States and is considered investigational. It is approved in Europe, and has pending approval in Australia, to treat patients with type 2 diabetes and/or obesity for 12 months.

GI Dynamics, the manufacturer of the device, sponsored the study. Dr. Pournaras did not present any financial disclosures.

BERLIN – A duodenal-jejunal liner seemed to improve glycemic control in patients with type 2 diabetes, a small prospective study has determined.

Among 16 patients who had the liner for 1 year, mean hemoglobin A_1c dropped more than 1% without any significant weight loss, Dr. Dimitri Pournaras said at the annual meeting of the European Association for the Study of Diabetes.

"Bypassing the gut seems to have an effect on glucose homeostasis that can’t be fully explained by weight loss," said Dr. Pournaras of Imperial College, London.

The flexible barrier attempts to mimic some of the benefits of gastric bypass without surgery, he said. The sleeve is endoscopically placed in the duodenal bulb and extends about 60 cm through the duodenum and proximal jejunum, preventing any nutrient contact with those regions.

Dr. Pournaras presented data on 16 nonobese patients with type 2 diabetes who had the gastric sleeve in place for 1 year.

At baseline, the patients had a body mass index of 23-36 kg/m² and were 35-65 years of age. The mean duration of disease was 2 years, and HbA_1c at baseline was 7.5%-10.2%. All of the patients were taking metformin; none were taking DPP-4 inhibitors, GLP-1 analogues, or insulin.

Investigators examined patients’ glycemic indicators at baseline and at 1, 12, and 52 weeks after the sleeve was placed. After an overnight fast, patients consumed a 525-calorie liquid meal. Blood was drawn before the meal and at 30, 60, 90, and 120 minutes afterward.

There were no significant changes in weight at any time after the surgery. In fact, Dr. Pounaras said, no patient experienced a change in the amount of food consumed.

HbA_1c was significantly lower at 3 months and stayed low throughout the study. At 52 weeks, the mean HbA_1c was 7.5%, compared with the mean of 8.6% at baseline. More than half of the subjects (62%) reached a level of 7%. Fasting glucose and acute glucose response improved significantly. Insulin sensitivity improved early and that was maintained. Insulin resistance, as measured by both the homeostasis model assessment of insulin resistance (HOMA-IR) and the Matsuda index, improved significantly by the end of the follow-up period. Insulin secretion and insulinogenic index were unchanged, as were C-peptide and fasting insulin, he reported.

Four patients experienced transient nausea and abdominal bloating after the sleeve was placed.

Dr. Pournaras did not say how many were able to come off of their metformin, nor did he mention the sleeve’s effect on any other drugs the patients may have been taking. In response to a question on this, he said that "metformin is a safe drug" that should not be used as the measure of diabetes remission.

The sleeve "opens the door to the possibility that we might one day be able to combine the duodenal-jejunal liner with medications such as GLP-1 agonists and DPP-4 inhibitors," Dr. Pournaras said.

The device is not approved for sale in the United States and is considered investigational. It is approved in Europe, and has pending approval in Australia, to treat patients with type 2 diabetes and/or obesity for 12 months.

GI Dynamics, the manufacturer of the device, sponsored the study. Dr. Pournaras did not present any financial disclosures.

Children conceived by frozen embryo transfer are significantly more likely to be large for gestational age at birth than those conceived naturally or by fresh embryo transfer.

Population-based studies from both France and Denmark have come to the same conclusion: Compared with fresh embryos, frozen embryos are up to 60% more likely to develop into large for gestational age (LGA) infants.

No one can yet be sure of the mechanism behind this finding, which also has been observed in Asian studies, Dr. Anja Pinborg said at the annual meeting of the European Society of Human Reproduction and Embryology. It may be related to the oocyte transfer, to keeping the embryo an extra day in the culture media, or even to something in the culture media itself.

"It may also be [an] example of epigenetic changes in the very early embryos caused by freezing and thawing," said Dr. Pinborg of Rigshospitalet, Copenhagen. "At this point all we have are theories. We need much more data to understand this. But I think it is important that we do understand more."

Dr. Pinborg presented the results of the Danish study, which included data on 910 singleton pregnancies conceived by frozen embryo transfer, 9,603 from fresh embryo transfer, and 4,656 conceived naturally.

The rate of LGA infants was 17% in the frozen embryo group – significantly higher than the 10% rate in the fresh embryo group and 11% rate in the natural conception group.

After adjusting for maternal age and parity, and the babies’ gender and birth year, frozen embryo infants were 60% more likely to be LGA than fresh embryo infants.

The number of infants with a birth weight of more than 4,500 g also was significantly higher in the frozen embryo group (6%) than in the fresh embryo and naturally conceived group (3% each).

"When we look at it from the other end – babies who are small for gestational age (SGA) – we see the reverse pattern," Dr. Pinborg said. The rate of SGA infants was 9% in the frozen embryo group, 15% in the fresh embryo group, and 11% in the naturally conceived group. After adjusting for the confounding factors, frozen embryo infants were 40% less likely to be SGA than fresh embryo infants.

The group also looked at the incidence of placenta previa – a factor associated with SGA infants. The incidence was 0.5% in the frozen embryo group, 1.5% in the fresh embryo group, and 0.3% in the naturally conceived group. The adjusted odds ratio of placenta previa was 2.8 for the frozen versus natural conception group and 5.0 for the fresh versus natural conception group.

Dr. Pinborg said the study has three key messages. "The first is a positive message: Children born after frozen embryo transfer have obstetrical outcomes similar to naturally conceived children. But our study also shows that these children are at a significantly increased risk of being large for gestational age and having a birth weight of more than 4,500 g. At this point, we don’t know the implications of this message. But in general, all children born by assisted reproductive technology do very well and have no problems."

The French study, presented by Dr. Sylvie Epelboin of the Bichat-Claude Bernard Hospital, Paris, came to similar conclusions about birth weight.

The French cohort consisted of 16,002 singleton pregnancies conceived by assisted reproductive technology (ART); 2,140 (13%) were frozen embryo transfer. The control group consisted of the 13,862 fresh embryo transfer pregnancies.

The gestational age at birth was slightly, but not significantly, younger in the frozen embryo group (39.1 vs. 39.3 weeks). The rate of preterm birth was also similar (8.6% in the frozen group and 8.3% in the fresh group). Neonatal mortality was less than 0.25% in each group.

Measures of weight were the only statistically significant between-group differences, Dr. Epelboin said.

The mean birth weight was 102 g higher in the frozen embryo group than in the fresh embryo group, while the incidence of low birth weight (less than 2,500 g) was significantly lower in the frozen embryo group.

Using the 90th percentile, the incidence of LGA births was significantly higher in the frozen embryo than the fresh embryo group (13% vs. 9%). The difference was also significant when comparing the 95th percentile (7% vs. 5%).

The good news, Dr. Epelboin said, is that embryo freezing does not adversely affect neonatal outcome, particularly in the risk of giving birth to a SGA infant.

Again, she said, there are only theories about the mechanism behind larger babies from frozen embryos. The finding may be related to the process of freezing and thawing, or perhaps to differences in the hormonal environment and its effect on the endometrium.

The study was sponsored by the ART Follow-Up Scientific Board. Dr. Epelboin said she had no relevant financial disclosures. Dr. Pinborg also reported no relevant financial disclosures.

Children conceived by frozen embryo transfer are significantly more likely to be large for gestational age at birth than those conceived naturally or by fresh embryo transfer.

Population-based studies from both France and Denmark have come to the same conclusion: Compared with fresh embryos, frozen embryos are up to 60% more likely to develop into large for gestational age (LGA) infants.

No one can yet be sure of the mechanism behind this finding, which also has been observed in Asian studies, Dr. Anja Pinborg said at the annual meeting of the European Society of Human Reproduction and Embryology. It may be related to the oocyte transfer, to keeping the embryo an extra day in the culture media, or even to something in the culture media itself.

"It may also be [an] example of epigenetic changes in the very early embryos caused by freezing and thawing," said Dr. Pinborg of Rigshospitalet, Copenhagen. "At this point all we have are theories. We need much more data to understand this. But I think it is important that we do understand more."

Dr. Pinborg presented the results of the Danish study, which included data on 910 singleton pregnancies conceived by frozen embryo transfer, 9,603 from fresh embryo transfer, and 4,656 conceived naturally.

The rate of LGA infants was 17% in the frozen embryo group – significantly higher than the 10% rate in the fresh embryo group and 11% rate in the natural conception group.

After adjusting for maternal age and parity, and the babies’ gender and birth year, frozen embryo infants were 60% more likely to be LGA than fresh embryo infants.

The number of infants with a birth weight of more than 4,500 g also was significantly higher in the frozen embryo group (6%) than in the fresh embryo and naturally conceived group (3% each).

"When we look at it from the other end – babies who are small for gestational age (SGA) – we see the reverse pattern," Dr. Pinborg said. The rate of SGA infants was 9% in the frozen embryo group, 15% in the fresh embryo group, and 11% in the naturally conceived group. After adjusting for the confounding factors, frozen embryo infants were 40% less likely to be SGA than fresh embryo infants.

The group also looked at the incidence of placenta previa – a factor associated with SGA infants. The incidence was 0.5% in the frozen embryo group, 1.5% in the fresh embryo group, and 0.3% in the naturally conceived group. The adjusted odds ratio of placenta previa was 2.8 for the frozen versus natural conception group and 5.0 for the fresh versus natural conception group.

Dr. Pinborg said the study has three key messages. "The first is a positive message: Children born after frozen embryo transfer have obstetrical outcomes similar to naturally conceived children. But our study also shows that these children are at a significantly increased risk of being large for gestational age and having a birth weight of more than 4,500 g. At this point, we don’t know the implications of this message. But in general, all children born by assisted reproductive technology do very well and have no problems."

The French study, presented by Dr. Sylvie Epelboin of the Bichat-Claude Bernard Hospital, Paris, came to similar conclusions about birth weight.

The French cohort consisted of 16,002 singleton pregnancies conceived by assisted reproductive technology (ART); 2,140 (13%) were frozen embryo transfer. The control group consisted of the 13,862 fresh embryo transfer pregnancies.

The gestational age at birth was slightly, but not significantly, younger in the frozen embryo group (39.1 vs. 39.3 weeks). The rate of preterm birth was also similar (8.6% in the frozen group and 8.3% in the fresh group). Neonatal mortality was less than 0.25% in each group.

Measures of weight were the only statistically significant between-group differences, Dr. Epelboin said.

The mean birth weight was 102 g higher in the frozen embryo group than in the fresh embryo group, while the incidence of low birth weight (less than 2,500 g) was significantly lower in the frozen embryo group.

Using the 90th percentile, the incidence of LGA births was significantly higher in the frozen embryo than the fresh embryo group (13% vs. 9%). The difference was also significant when comparing the 95th percentile (7% vs. 5%).

The good news, Dr. Epelboin said, is that embryo freezing does not adversely affect neonatal outcome, particularly in the risk of giving birth to a SGA infant.

Again, she said, there are only theories about the mechanism behind larger babies from frozen embryos. The finding may be related to the process of freezing and thawing, or perhaps to differences in the hormonal environment and its effect on the endometrium.

The study was sponsored by the ART Follow-Up Scientific Board. Dr. Epelboin said she had no relevant financial disclosures. Dr. Pinborg also reported no relevant financial disclosures.

Children conceived by frozen embryo transfer are significantly more likely to be large for gestational age at birth than those conceived naturally or by fresh embryo transfer.

Population-based studies from both France and Denmark have come to the same conclusion: Compared with fresh embryos, frozen embryos are up to 60% more likely to develop into large for gestational age (LGA) infants.

No one can yet be sure of the mechanism behind this finding, which also has been observed in Asian studies, Dr. Anja Pinborg said at the annual meeting of the European Society of Human Reproduction and Embryology. It may be related to the oocyte transfer, to keeping the embryo an extra day in the culture media, or even to something in the culture media itself.

"It may also be [an] example of epigenetic changes in the very early embryos caused by freezing and thawing," said Dr. Pinborg of Rigshospitalet, Copenhagen. "At this point all we have are theories. We need much more data to understand this. But I think it is important that we do understand more."

Dr. Pinborg presented the results of the Danish study, which included data on 910 singleton pregnancies conceived by frozen embryo transfer, 9,603 from fresh embryo transfer, and 4,656 conceived naturally.

The rate of LGA infants was 17% in the frozen embryo group – significantly higher than the 10% rate in the fresh embryo group and 11% rate in the natural conception group.

After adjusting for maternal age and parity, and the babies’ gender and birth year, frozen embryo infants were 60% more likely to be LGA than fresh embryo infants.

The number of infants with a birth weight of more than 4,500 g also was significantly higher in the frozen embryo group (6%) than in the fresh embryo and naturally conceived group (3% each).

"When we look at it from the other end – babies who are small for gestational age (SGA) – we see the reverse pattern," Dr. Pinborg said. The rate of SGA infants was 9% in the frozen embryo group, 15% in the fresh embryo group, and 11% in the naturally conceived group. After adjusting for the confounding factors, frozen embryo infants were 40% less likely to be SGA than fresh embryo infants.

The group also looked at the incidence of placenta previa – a factor associated with SGA infants. The incidence was 0.5% in the frozen embryo group, 1.5% in the fresh embryo group, and 0.3% in the naturally conceived group. The adjusted odds ratio of placenta previa was 2.8 for the frozen versus natural conception group and 5.0 for the fresh versus natural conception group.

Dr. Pinborg said the study has three key messages. "The first is a positive message: Children born after frozen embryo transfer have obstetrical outcomes similar to naturally conceived children. But our study also shows that these children are at a significantly increased risk of being large for gestational age and having a birth weight of more than 4,500 g. At this point, we don’t know the implications of this message. But in general, all children born by assisted reproductive technology do very well and have no problems."

The French study, presented by Dr. Sylvie Epelboin of the Bichat-Claude Bernard Hospital, Paris, came to similar conclusions about birth weight.

The French cohort consisted of 16,002 singleton pregnancies conceived by assisted reproductive technology (ART); 2,140 (13%) were frozen embryo transfer. The control group consisted of the 13,862 fresh embryo transfer pregnancies.

The gestational age at birth was slightly, but not significantly, younger in the frozen embryo group (39.1 vs. 39.3 weeks). The rate of preterm birth was also similar (8.6% in the frozen group and 8.3% in the fresh group). Neonatal mortality was less than 0.25% in each group.

Measures of weight were the only statistically significant between-group differences, Dr. Epelboin said.

The mean birth weight was 102 g higher in the frozen embryo group than in the fresh embryo group, while the incidence of low birth weight (less than 2,500 g) was significantly lower in the frozen embryo group.

Using the 90th percentile, the incidence of LGA births was significantly higher in the frozen embryo than the fresh embryo group (13% vs. 9%). The difference was also significant when comparing the 95th percentile (7% vs. 5%).

The good news, Dr. Epelboin said, is that embryo freezing does not adversely affect neonatal outcome, particularly in the risk of giving birth to a SGA infant.

Again, she said, there are only theories about the mechanism behind larger babies from frozen embryos. The finding may be related to the process of freezing and thawing, or perhaps to differences in the hormonal environment and its effect on the endometrium.

The study was sponsored by the ART Follow-Up Scientific Board. Dr. Epelboin said she had no relevant financial disclosures. Dr. Pinborg also reported no relevant financial disclosures.

GRAPEVINE, TX – In its first year of operation, a hospitalist-created telemedicine stroke center has reported patient outcomes – including timely thrombolytic therapy and mortality – that are at least as good as those seen among all such centers included in the American Stroke Association’s database.

Dr. Karim B. Godamunne, founder and medical director of the Certified Advanced Primary Stroke Center at South Fulton Medical Center, East Point, Ga., presented the center’s first-year outcomes at the annual meeting of the Society for Hospital Medicine.

South Fulton is an predominately black community near Atlanta that is medically underserved, with a shortage of neurologists and experts in stroke care, but rich in patients with an increased stroke risk said Dr. Godamunne, who is also director of hospital medicine there. "We needed some kind of way to provide good stroke care for our patients."

An attempt to create a stroke center at South Fulton several years ago failed, he said in an interview, mainly because most neurologists in the area work only in outpatient settings. After creating the hospitalist program at South in 2007, Dr. Godamunne was ready to try implementing a new concept – combining the clinical expertise of hospitalists and telemedicine to build a stroke center

In 2009, the American Stroke Association consensus statement found telemedicine an excellent way to improve stroke care, especially in underserved areas or when a neurologist is not available in the hospital.

South Fulton seemed like a perfect fit for this treatment paradigm. Working closely with Eagle Hospital Physicians of Atlanta and South Fulton Medical Center, Dr. Godamunne installed a telemedicine unit that provides a live video link with stroke specialists, who are available around the clock. The telestroke unit has a wheeled computer workstation with a two-way video camera and microphone, a large display screen, and a wireless Internet connection. The remote physician operates it from a laptop equipped with a joystick, moving the camera and video screen up, down, and side to side. The system also allows the entire unit to roll unassisted through the hall and into a patient’s room

It can be equipped with a stethoscope, which a bedside attending or a nurse use normally, while the remote physician sees and hears the information detected. Remote physicians can examine the patient almost as if they were in the room, said Dr. Godamunne, who is also who is also the vice-president of clinical systems integration for Eagle Hospital Physicians. The system allows for faster decision making at a critical time, he said. However, he added, a robot – even one with a neurologist manning it – can’t completely replace the bedside clinician: "In-house neurology coverage is still essential, but by leveraging telemedicine and hospitalists, we can build a stroke center with far fewer neurologists than previously required.

"Treating stroke isn’t just about giving thrombolytics, but preventing hospital complications like pneumonia and deep-vein thrombosis, and discharging patients on medical therapies that can prevent a subsequent stroke."

"The key part in developing this type of telestroke system is that you must have a physician in-house to coordinate other aspects of care," Dr. Godamunne said. "This is where the hospitalist comes in. We issue the orders based on the ‘Get With the Guidelines’ criteria and put all the protocol into one place."

Photo credit: Dr. Karim B. Godamunne

Hospitalists improved their expertise in managing stroke patients through training, operational procedures, protocol development and collaboration with the teleneurologists.

After 6 months of use, South Fulton’s integrated hospitalist telestroke program earned the Joint Commission’s certification as an Advanced Primary Stroke Center. Within a year, it had received American Stroke Association’s Silver Plus status – the highest honor achievable for a first-year stroke program.

To examine the program’s effectiveness, Dr. Godamunne compared its 1-year outcomes with those of patients treated during the same time, recorded in the "Get With the Guidelines" database. The study compared length of stay and mortality, and also eight primary stroke center score measures:

• DVT prophylaxis by day 2.
• Antithrombotic therapy at discharge.
• Anticoagulation therapy for ischemic stroke patients who have atrial fibrillation/flutter.
• Tissue plasminogen activator given within 2 hours of hospital arrival and 3 hours of onset.
• Antithrombotic therapy by day 2 of admission.
• Statins for patients with high low-density lipoprotein cholesterol.
• Stroke education for patients and their caregivers.
• Patient assessment for rehabilitation.

Over the first year, hospitalists cared for 70% (168) of the 240 patients admitted for possible stroke at the South Fulton telestroke center; 158 of these were discharged with a diagnosis of stroke – a 75% increase over the previous year.

Ten patients qualified for tissue plasminogen activator treatment, with TPA given up to 4.5 hours past the last known time of being well. Dr. Godamunne noted that in the prior 2 years, no stroke patients admitted to South Fulton received TPA.

The increase in diagnoses, coupled with demographic factors, speaks to the enormous health problem in the South Fulton community, Dr. Godamunne said: 80% of the patients treated at the new stroke center were black – a known high-risk group for stroke.

"The need for acute and preventive stroke care was not being met in this community of 500,000, in part because patients had to travel an additional 30-45 minutes to a stroke center. In my hospitalist group, stroke was not even in the top 20 of our diagnoses – now it’s number 4, and the impact on us and the hospital has been huge."

In the comparison, mortality was slightly – but not significantly – lower at South Fulton (3% vs. 7%). "This was probably because we did not admit patients with intracranial hemorrhage," Dr. Godamunne noted. Patients presenting with suspected intracranial bleeding were taken to a sister hospital with constant neurosurgical capability.

Among the primary stroke care core measures, South Fulton stacked up well, matching or exceeding the aggregate in all eight measures, with no statistically significant differences.

The experience shows that a hospitalist can build and lead a stroke center, Dr. Godamunne said.

"Patients who were at a higher risk for stroke based on race and demographics can realize the benefits of thrombolytics and all the long-term preventive benefits of meeting all other stroke center guidelines."

GRAPEVINE, TX – In its first year of operation, a hospitalist-created telemedicine stroke center has reported patient outcomes – including timely thrombolytic therapy and mortality – that are at least as good as those seen among all such centers included in the American Stroke Association’s database.

Dr. Karim B. Godamunne, founder and medical director of the Certified Advanced Primary Stroke Center at South Fulton Medical Center, East Point, Ga., presented the center’s first-year outcomes at the annual meeting of the Society for Hospital Medicine.

South Fulton is an predominately black community near Atlanta that is medically underserved, with a shortage of neurologists and experts in stroke care, but rich in patients with an increased stroke risk said Dr. Godamunne, who is also director of hospital medicine there. "We needed some kind of way to provide good stroke care for our patients."

An attempt to create a stroke center at South Fulton several years ago failed, he said in an interview, mainly because most neurologists in the area work only in outpatient settings. After creating the hospitalist program at South in 2007, Dr. Godamunne was ready to try implementing a new concept – combining the clinical expertise of hospitalists and telemedicine to build a stroke center

In 2009, the American Stroke Association consensus statement found telemedicine an excellent way to improve stroke care, especially in underserved areas or when a neurologist is not available in the hospital.

South Fulton seemed like a perfect fit for this treatment paradigm. Working closely with Eagle Hospital Physicians of Atlanta and South Fulton Medical Center, Dr. Godamunne installed a telemedicine unit that provides a live video link with stroke specialists, who are available around the clock. The telestroke unit has a wheeled computer workstation with a two-way video camera and microphone, a large display screen, and a wireless Internet connection. The remote physician operates it from a laptop equipped with a joystick, moving the camera and video screen up, down, and side to side. The system also allows the entire unit to roll unassisted through the hall and into a patient’s room

It can be equipped with a stethoscope, which a bedside attending or a nurse use normally, while the remote physician sees and hears the information detected. Remote physicians can examine the patient almost as if they were in the room, said Dr. Godamunne, who is also who is also the vice-president of clinical systems integration for Eagle Hospital Physicians. The system allows for faster decision making at a critical time, he said. However, he added, a robot – even one with a neurologist manning it – can’t completely replace the bedside clinician: "In-house neurology coverage is still essential, but by leveraging telemedicine and hospitalists, we can build a stroke center with far fewer neurologists than previously required.

"Treating stroke isn’t just about giving thrombolytics, but preventing hospital complications like pneumonia and deep-vein thrombosis, and discharging patients on medical therapies that can prevent a subsequent stroke."

"The key part in developing this type of telestroke system is that you must have a physician in-house to coordinate other aspects of care," Dr. Godamunne said. "This is where the hospitalist comes in. We issue the orders based on the ‘Get With the Guidelines’ criteria and put all the protocol into one place."

Photo credit: Dr. Karim B. Godamunne

Hospitalists improved their expertise in managing stroke patients through training, operational procedures, protocol development and collaboration with the teleneurologists.

After 6 months of use, South Fulton’s integrated hospitalist telestroke program earned the Joint Commission’s certification as an Advanced Primary Stroke Center. Within a year, it had received American Stroke Association’s Silver Plus status – the highest honor achievable for a first-year stroke program.

To examine the program’s effectiveness, Dr. Godamunne compared its 1-year outcomes with those of patients treated during the same time, recorded in the "Get With the Guidelines" database. The study compared length of stay and mortality, and also eight primary stroke center score measures:

• DVT prophylaxis by day 2.
• Antithrombotic therapy at discharge.
• Anticoagulation therapy for ischemic stroke patients who have atrial fibrillation/flutter.
• Tissue plasminogen activator given within 2 hours of hospital arrival and 3 hours of onset.
• Antithrombotic therapy by day 2 of admission.
• Statins for patients with high low-density lipoprotein cholesterol.
• Stroke education for patients and their caregivers.
• Patient assessment for rehabilitation.

Over the first year, hospitalists cared for 70% (168) of the 240 patients admitted for possible stroke at the South Fulton telestroke center; 158 of these were discharged with a diagnosis of stroke – a 75% increase over the previous year.

Ten patients qualified for tissue plasminogen activator treatment, with TPA given up to 4.5 hours past the last known time of being well. Dr. Godamunne noted that in the prior 2 years, no stroke patients admitted to South Fulton received TPA.

The increase in diagnoses, coupled with demographic factors, speaks to the enormous health problem in the South Fulton community, Dr. Godamunne said: 80% of the patients treated at the new stroke center were black – a known high-risk group for stroke.

"The need for acute and preventive stroke care was not being met in this community of 500,000, in part because patients had to travel an additional 30-45 minutes to a stroke center. In my hospitalist group, stroke was not even in the top 20 of our diagnoses – now it’s number 4, and the impact on us and the hospital has been huge."

In the comparison, mortality was slightly – but not significantly – lower at South Fulton (3% vs. 7%). "This was probably because we did not admit patients with intracranial hemorrhage," Dr. Godamunne noted. Patients presenting with suspected intracranial bleeding were taken to a sister hospital with constant neurosurgical capability.

Among the primary stroke care core measures, South Fulton stacked up well, matching or exceeding the aggregate in all eight measures, with no statistically significant differences.

The experience shows that a hospitalist can build and lead a stroke center, Dr. Godamunne said.

"Patients who were at a higher risk for stroke based on race and demographics can realize the benefits of thrombolytics and all the long-term preventive benefits of meeting all other stroke center guidelines."

GRAPEVINE, TX – In its first year of operation, a hospitalist-created telemedicine stroke center has reported patient outcomes – including timely thrombolytic therapy and mortality – that are at least as good as those seen among all such centers included in the American Stroke Association’s database.

Dr. Karim B. Godamunne, founder and medical director of the Certified Advanced Primary Stroke Center at South Fulton Medical Center, East Point, Ga., presented the center’s first-year outcomes at the annual meeting of the Society for Hospital Medicine.

South Fulton is an predominately black community near Atlanta that is medically underserved, with a shortage of neurologists and experts in stroke care, but rich in patients with an increased stroke risk said Dr. Godamunne, who is also director of hospital medicine there. "We needed some kind of way to provide good stroke care for our patients."

An attempt to create a stroke center at South Fulton several years ago failed, he said in an interview, mainly because most neurologists in the area work only in outpatient settings. After creating the hospitalist program at South in 2007, Dr. Godamunne was ready to try implementing a new concept – combining the clinical expertise of hospitalists and telemedicine to build a stroke center

In 2009, the American Stroke Association consensus statement found telemedicine an excellent way to improve stroke care, especially in underserved areas or when a neurologist is not available in the hospital.

South Fulton seemed like a perfect fit for this treatment paradigm. Working closely with Eagle Hospital Physicians of Atlanta and South Fulton Medical Center, Dr. Godamunne installed a telemedicine unit that provides a live video link with stroke specialists, who are available around the clock. The telestroke unit has a wheeled computer workstation with a two-way video camera and microphone, a large display screen, and a wireless Internet connection. The remote physician operates it from a laptop equipped with a joystick, moving the camera and video screen up, down, and side to side. The system also allows the entire unit to roll unassisted through the hall and into a patient’s room

It can be equipped with a stethoscope, which a bedside attending or a nurse use normally, while the remote physician sees and hears the information detected. Remote physicians can examine the patient almost as if they were in the room, said Dr. Godamunne, who is also who is also the vice-president of clinical systems integration for Eagle Hospital Physicians. The system allows for faster decision making at a critical time, he said. However, he added, a robot – even one with a neurologist manning it – can’t completely replace the bedside clinician: "In-house neurology coverage is still essential, but by leveraging telemedicine and hospitalists, we can build a stroke center with far fewer neurologists than previously required.

"Treating stroke isn’t just about giving thrombolytics, but preventing hospital complications like pneumonia and deep-vein thrombosis, and discharging patients on medical therapies that can prevent a subsequent stroke."

"The key part in developing this type of telestroke system is that you must have a physician in-house to coordinate other aspects of care," Dr. Godamunne said. "This is where the hospitalist comes in. We issue the orders based on the ‘Get With the Guidelines’ criteria and put all the protocol into one place."

Photo credit: Dr. Karim B. Godamunne

Hospitalists improved their expertise in managing stroke patients through training, operational procedures, protocol development and collaboration with the teleneurologists.

After 6 months of use, South Fulton’s integrated hospitalist telestroke program earned the Joint Commission’s certification as an Advanced Primary Stroke Center. Within a year, it had received American Stroke Association’s Silver Plus status – the highest honor achievable for a first-year stroke program.

To examine the program’s effectiveness, Dr. Godamunne compared its 1-year outcomes with those of patients treated during the same time, recorded in the "Get With the Guidelines" database. The study compared length of stay and mortality, and also eight primary stroke center score measures:

• DVT prophylaxis by day 2.
• Antithrombotic therapy at discharge.
• Anticoagulation therapy for ischemic stroke patients who have atrial fibrillation/flutter.
• Tissue plasminogen activator given within 2 hours of hospital arrival and 3 hours of onset.
• Antithrombotic therapy by day 2 of admission.
• Statins for patients with high low-density lipoprotein cholesterol.
• Stroke education for patients and their caregivers.
• Patient assessment for rehabilitation.

Over the first year, hospitalists cared for 70% (168) of the 240 patients admitted for possible stroke at the South Fulton telestroke center; 158 of these were discharged with a diagnosis of stroke – a 75% increase over the previous year.

Ten patients qualified for tissue plasminogen activator treatment, with TPA given up to 4.5 hours past the last known time of being well. Dr. Godamunne noted that in the prior 2 years, no stroke patients admitted to South Fulton received TPA.

The increase in diagnoses, coupled with demographic factors, speaks to the enormous health problem in the South Fulton community, Dr. Godamunne said: 80% of the patients treated at the new stroke center were black – a known high-risk group for stroke.

"The need for acute and preventive stroke care was not being met in this community of 500,000, in part because patients had to travel an additional 30-45 minutes to a stroke center. In my hospitalist group, stroke was not even in the top 20 of our diagnoses – now it’s number 4, and the impact on us and the hospital has been huge."

In the comparison, mortality was slightly – but not significantly – lower at South Fulton (3% vs. 7%). "This was probably because we did not admit patients with intracranial hemorrhage," Dr. Godamunne noted. Patients presenting with suspected intracranial bleeding were taken to a sister hospital with constant neurosurgical capability.

Among the primary stroke care core measures, South Fulton stacked up well, matching or exceeding the aggregate in all eight measures, with no statistically significant differences.

The experience shows that a hospitalist can build and lead a stroke center, Dr. Godamunne said.

"Patients who were at a higher risk for stroke based on race and demographics can realize the benefits of thrombolytics and all the long-term preventive benefits of meeting all other stroke center guidelines."

SAN DIEGO – In two new position papers, the American College of Physicians declared support for both Medicaid reform and legislation that would provide broader health care access for immigrants – regardless of their legal status.

Although not suggesting that U.S. taxpayers support the health care costs of undocumented aliens, the policy statement does recommend open access to comprehensive primary and preventive care – including vaccinations, prenatal and obstetrical care, and screening for preventable illness. Providing these services would not only reduce the cost burden associated with emergency room treatment when undocumented immigrants are acutely ill, it would help protect citizens who might be exposed to untreated, communicable disease, Dr. J. Fred Ralston Jr., immediate past president of the American College of Physicians, said at the group’s annual meeting

Tuberculosis is a case in point, he said at a press briefing. "Under the current system, [illegal immigrants] may be afraid that going to a hospital to seek treatment would place them at risk of deportation. If they delay care because of this fear, it could increase the number of people exposed to the diseases exponentially."

The 18-page paper is not a broad-based effort to address the overall problem of illegal immigration. Instead, Dr. Ralston said, it asks for a national policy that upholds the ethical responsibility of both physicians and the government to provide nondiscriminatory care to all people within U.S. borders.

"Any national immigration policy will need to balance the legitimate needs and concerns to control our borders and to equitably differentiate publicly supported services for those who fully comply with immigration laws and those who do not," he said. "However, access to health care for immigrants is crucial to the overall population of the U.S. We all have a vested interest in ensuring that all residents have access to necessary care."

The paper does not address the financial means by which such recommendations might be implemented. It does, however, stress that "[Immigrants without legal status] should not be prevented from paying out-of-pocket to cover their expenses, including the ability to purchase coverage at their own expense from the state health exchanges that will be created under the Affordable Care Act."

Further, Dr. Ralston, an internist in Fayetteville, Tenn., said that any national health policy should automatically cover native-born children of illegal aliens. "U.S.-born children of illegal residents should have the same access to purchased insurance and government-subsidized health care as any other U.S. citizen," according to the policy paper.

The college also unveiled recommendations for reforming Medicaid, focused on improving access to care for the millions who are, and will shortly become, eligible for its benefits.

‘The need for an improved Medicaid program was made evident during the recent recession, when almost 4 million people – the largest increase ever – found themselves relying on Medicaid for health care coverage," Dr. Ralston said. "Medicaid faces the potential of increasing enrollment of up to 18 million by 2019, with 10 states projecting a 50% increase."

But, he said, "With challenge comes the opportunity to improve Medicaid, with regard to its access and future sustainability."

The 38-page paper puts forth 12 recommendations, some of which concentrate on improving Medicaid payments to physicians. These, the paper says, are the foundations upon which a sound Medicaid program must be rebuilt. Among the paper’s recommendations:

• Standardize Medicaid minimum eligibility and fully subsidize federally mandated Medicaid coverage expansions. Without this, states will be forced to make up the gap, and patients will take the financial hit, said Robert B. Doherty, senior vice president of governmental affairs and public policy for the ACP;

• Offer more flexibility in long-term care choices, since alternatives can be less expensive than nursing homes;

• Streamline and improve the Medicaid waiver process, to ensure timely approval or rejection of waiver requests. Doing so may help ensure that more eligible patients enroll and take advantage of the program;

• Focus more on Medicaid programs that improve quality of care to minorities and effectively manage chronic disease and mental health disorders;

• Institute countercyclical funding to increase the amount of federal dollars available during economic downturns;

• Reduce enrollment barriers by state and federal cooperation. Such an effort would make enrollment easier and help ensure timely access to health care.

"The Medicaid system provides vital health services to vulnerable populations," Dr. Ralston said. "But like the health care system as a whole, Medicaid needs to be improved to emphasize preventive and primary care."

The paper calls for permanent Medicaid payment increases to primary care physicians and other specialist services, to at least the level of Medicare reimbursement

On the issue of anticipated budget cuts, Mr. Doherty added that the government should financially uphold programs to support physician recruitment and training, especially in light of expected primary care shortages. "Cutting programs to train more primary care providers would be penny-wise but pound-foolish. ... If Congress does not support these programs, we will face greater shortages, longer waits for appointments, and higher, budget-busting health care spending."

Dr. Ralston and Mr. Doherty reported having no disclosures.

SAN DIEGO – In two new position papers, the American College of Physicians declared support for both Medicaid reform and legislation that would provide broader health care access for immigrants – regardless of their legal status.

Although not suggesting that U.S. taxpayers support the health care costs of undocumented aliens, the policy statement does recommend open access to comprehensive primary and preventive care – including vaccinations, prenatal and obstetrical care, and screening for preventable illness. Providing these services would not only reduce the cost burden associated with emergency room treatment when undocumented immigrants are acutely ill, it would help protect citizens who might be exposed to untreated, communicable disease, Dr. J. Fred Ralston Jr., immediate past president of the American College of Physicians, said at the group’s annual meeting

Tuberculosis is a case in point, he said at a press briefing. "Under the current system, [illegal immigrants] may be afraid that going to a hospital to seek treatment would place them at risk of deportation. If they delay care because of this fear, it could increase the number of people exposed to the diseases exponentially."

The 18-page paper is not a broad-based effort to address the overall problem of illegal immigration. Instead, Dr. Ralston said, it asks for a national policy that upholds the ethical responsibility of both physicians and the government to provide nondiscriminatory care to all people within U.S. borders.

"Any national immigration policy will need to balance the legitimate needs and concerns to control our borders and to equitably differentiate publicly supported services for those who fully comply with immigration laws and those who do not," he said. "However, access to health care for immigrants is crucial to the overall population of the U.S. We all have a vested interest in ensuring that all residents have access to necessary care."

The paper does not address the financial means by which such recommendations might be implemented. It does, however, stress that "[Immigrants without legal status] should not be prevented from paying out-of-pocket to cover their expenses, including the ability to purchase coverage at their own expense from the state health exchanges that will be created under the Affordable Care Act."

Further, Dr. Ralston, an internist in Fayetteville, Tenn., said that any national health policy should automatically cover native-born children of illegal aliens. "U.S.-born children of illegal residents should have the same access to purchased insurance and government-subsidized health care as any other U.S. citizen," according to the policy paper.

The college also unveiled recommendations for reforming Medicaid, focused on improving access to care for the millions who are, and will shortly become, eligible for its benefits.

‘The need for an improved Medicaid program was made evident during the recent recession, when almost 4 million people – the largest increase ever – found themselves relying on Medicaid for health care coverage," Dr. Ralston said. "Medicaid faces the potential of increasing enrollment of up to 18 million by 2019, with 10 states projecting a 50% increase."

But, he said, "With challenge comes the opportunity to improve Medicaid, with regard to its access and future sustainability."

The 38-page paper puts forth 12 recommendations, some of which concentrate on improving Medicaid payments to physicians. These, the paper says, are the foundations upon which a sound Medicaid program must be rebuilt. Among the paper’s recommendations:

• Standardize Medicaid minimum eligibility and fully subsidize federally mandated Medicaid coverage expansions. Without this, states will be forced to make up the gap, and patients will take the financial hit, said Robert B. Doherty, senior vice president of governmental affairs and public policy for the ACP;

• Offer more flexibility in long-term care choices, since alternatives can be less expensive than nursing homes;

• Streamline and improve the Medicaid waiver process, to ensure timely approval or rejection of waiver requests. Doing so may help ensure that more eligible patients enroll and take advantage of the program;

• Focus more on Medicaid programs that improve quality of care to minorities and effectively manage chronic disease and mental health disorders;

• Institute countercyclical funding to increase the amount of federal dollars available during economic downturns;

• Reduce enrollment barriers by state and federal cooperation. Such an effort would make enrollment easier and help ensure timely access to health care.

"The Medicaid system provides vital health services to vulnerable populations," Dr. Ralston said. "But like the health care system as a whole, Medicaid needs to be improved to emphasize preventive and primary care."

The paper calls for permanent Medicaid payment increases to primary care physicians and other specialist services, to at least the level of Medicare reimbursement

On the issue of anticipated budget cuts, Mr. Doherty added that the government should financially uphold programs to support physician recruitment and training, especially in light of expected primary care shortages. "Cutting programs to train more primary care providers would be penny-wise but pound-foolish. ... If Congress does not support these programs, we will face greater shortages, longer waits for appointments, and higher, budget-busting health care spending."

Dr. Ralston and Mr. Doherty reported having no disclosures.

SAN DIEGO – In two new position papers, the American College of Physicians declared support for both Medicaid reform and legislation that would provide broader health care access for immigrants – regardless of their legal status.

Although not suggesting that U.S. taxpayers support the health care costs of undocumented aliens, the policy statement does recommend open access to comprehensive primary and preventive care – including vaccinations, prenatal and obstetrical care, and screening for preventable illness. Providing these services would not only reduce the cost burden associated with emergency room treatment when undocumented immigrants are acutely ill, it would help protect citizens who might be exposed to untreated, communicable disease, Dr. J. Fred Ralston Jr., immediate past president of the American College of Physicians, said at the group’s annual meeting

Tuberculosis is a case in point, he said at a press briefing. "Under the current system, [illegal immigrants] may be afraid that going to a hospital to seek treatment would place them at risk of deportation. If they delay care because of this fear, it could increase the number of people exposed to the diseases exponentially."

The 18-page paper is not a broad-based effort to address the overall problem of illegal immigration. Instead, Dr. Ralston said, it asks for a national policy that upholds the ethical responsibility of both physicians and the government to provide nondiscriminatory care to all people within U.S. borders.

"Any national immigration policy will need to balance the legitimate needs and concerns to control our borders and to equitably differentiate publicly supported services for those who fully comply with immigration laws and those who do not," he said. "However, access to health care for immigrants is crucial to the overall population of the U.S. We all have a vested interest in ensuring that all residents have access to necessary care."

The paper does not address the financial means by which such recommendations might be implemented. It does, however, stress that "[Immigrants without legal status] should not be prevented from paying out-of-pocket to cover their expenses, including the ability to purchase coverage at their own expense from the state health exchanges that will be created under the Affordable Care Act."

Further, Dr. Ralston, an internist in Fayetteville, Tenn., said that any national health policy should automatically cover native-born children of illegal aliens. "U.S.-born children of illegal residents should have the same access to purchased insurance and government-subsidized health care as any other U.S. citizen," according to the policy paper.

The college also unveiled recommendations for reforming Medicaid, focused on improving access to care for the millions who are, and will shortly become, eligible for its benefits.

‘The need for an improved Medicaid program was made evident during the recent recession, when almost 4 million people – the largest increase ever – found themselves relying on Medicaid for health care coverage," Dr. Ralston said. "Medicaid faces the potential of increasing enrollment of up to 18 million by 2019, with 10 states projecting a 50% increase."

But, he said, "With challenge comes the opportunity to improve Medicaid, with regard to its access and future sustainability."

The 38-page paper puts forth 12 recommendations, some of which concentrate on improving Medicaid payments to physicians. These, the paper says, are the foundations upon which a sound Medicaid program must be rebuilt. Among the paper’s recommendations:

• Standardize Medicaid minimum eligibility and fully subsidize federally mandated Medicaid coverage expansions. Without this, states will be forced to make up the gap, and patients will take the financial hit, said Robert B. Doherty, senior vice president of governmental affairs and public policy for the ACP;

• Offer more flexibility in long-term care choices, since alternatives can be less expensive than nursing homes;

• Streamline and improve the Medicaid waiver process, to ensure timely approval or rejection of waiver requests. Doing so may help ensure that more eligible patients enroll and take advantage of the program;

• Focus more on Medicaid programs that improve quality of care to minorities and effectively manage chronic disease and mental health disorders;

• Institute countercyclical funding to increase the amount of federal dollars available during economic downturns;

• Reduce enrollment barriers by state and federal cooperation. Such an effort would make enrollment easier and help ensure timely access to health care.

"The Medicaid system provides vital health services to vulnerable populations," Dr. Ralston said. "But like the health care system as a whole, Medicaid needs to be improved to emphasize preventive and primary care."

The paper calls for permanent Medicaid payment increases to primary care physicians and other specialist services, to at least the level of Medicare reimbursement

On the issue of anticipated budget cuts, Mr. Doherty added that the government should financially uphold programs to support physician recruitment and training, especially in light of expected primary care shortages. "Cutting programs to train more primary care providers would be penny-wise but pound-foolish. ... If Congress does not support these programs, we will face greater shortages, longer waits for appointments, and higher, budget-busting health care spending."

Dr. Ralston and Mr. Doherty reported having no disclosures.

SAN DIEGO – In two new position papers, the American College of Physicians declared support for both Medicaid reform and legislation that would provide broader health care access for immigrants – regardless of their legal status.

Although not suggesting that U.S. taxpayers support the health care costs of undocumented aliens, the policy statement does recommend open access to comprehensive primary and preventive care – including vaccinations, prenatal and obstetrical care, and screening for preventable illness. Providing these services would not only reduce the cost burden associated with emergency room treatment when undocumented immigrants are acutely ill, it would help protect citizens who might be exposed to untreated, communicable disease, Dr. J. Fred Ralston Jr., immediate past president of the American College of Physicians, said at the group’s annual meeting

Tuberculosis is a case in point, he said at a press briefing. "Under the current system, [illegal immigrants] may be afraid that going to a hospital to seek treatment would place them at risk of deportation. If they delay care because of this fear, it could increase the number of people exposed to the diseases exponentially."

The 18-page paper is not a broad-based effort to address the overall problem of illegal immigration. Instead, Dr. Ralston said, it asks for a national policy that upholds the ethical responsibility of both physicians and the government to provide nondiscriminatory care to all people within U.S. borders.

"Any national immigration policy will need to balance the legitimate needs and concerns to control our borders and to equitably differentiate publicly supported services for those who fully comply with immigration laws and those who do not," he said. "However, access to health care for immigrants is crucial to the overall population of the U.S. We all have a vested interest in ensuring that all residents have access to necessary care."

The paper does not address the financial means by which such recommendations might be implemented. It does, however, stress that "[Immigrants without legal status] should not be prevented from paying out-of-pocket to cover their expenses, including the ability to purchase coverage at their own expense from the state health exchanges that will be created under the Affordable Care Act."

Further, Dr. Ralston, an internist in Fayetteville, Tenn., said that any national health policy should automatically cover native-born children of illegal aliens. "U.S.-born children of illegal residents should have the same access to purchased insurance and government-subsidized health care as any other U.S. citizen," according to the policy paper.

The college also unveiled recommendations for reforming Medicaid, focused on improving access to care for the millions who are, and will shortly become, eligible for its benefits.

‘The need for an improved Medicaid program was made evident during the recent recession, when almost 4 million people – the largest increase ever – found themselves relying on Medicaid for health care coverage," Dr. Ralston said. "Medicaid faces the potential of increasing enrollment of up to 18 million by 2019, with 10 states projecting a 50% increase."

But, he said, "With challenge comes the opportunity to improve Medicaid, with regard to its access and future sustainability."

The 38-page paper puts forth 12 recommendations, some of which concentrate on improving Medicaid payments to physicians. These, the paper says, are the foundations upon which a sound Medicaid program must be rebuilt. Among the paper’s recommendations:

• Standardize Medicaid minimum eligibility and fully subsidize federally mandated Medicaid coverage expansions. Without this, states will be forced to make up the gap, and patients will take the financial hit, said Robert B. Doherty, senior vice president of governmental affairs and public policy for the ACP;

• Offer more flexibility in long-term care choices, since alternatives can be less expensive than nursing homes;

• Streamline and improve the Medicaid waiver process, to ensure timely approval or rejection of waiver requests. Doing so may help ensure that more eligible patients enroll and take advantage of the program;

• Focus more on Medicaid programs that improve quality of care to minorities and effectively manage chronic disease and mental health disorders;

• Institute countercyclical funding to increase the amount of federal dollars available during economic downturns;

• Reduce enrollment barriers by state and federal cooperation. Such an effort would make enrollment easier and help ensure timely access to health care.

"The Medicaid system provides vital health services to vulnerable populations," Dr. Ralston said. "But like the health care system as a whole, Medicaid needs to be improved to emphasize preventive and primary care."

The paper calls for permanent Medicaid payment increases to primary care physicians and other specialist services, to at least the level of Medicare reimbursement

On the issue of anticipated budget cuts, Mr. Doherty added that the government should financially uphold programs to support physician recruitment and training, especially in light of expected primary care shortages. "Cutting programs to train more primary care providers would be penny-wise but pound-foolish. ... If Congress does not support these programs, we will face greater shortages, longer waits for appointments, and higher, budget-busting health care spending."

Dr. Ralston and Mr. Doherty reported having no disclosures.

SAN DIEGO – In two new position papers, the American College of Physicians declared support for both Medicaid reform and legislation that would provide broader health care access for immigrants – regardless of their legal status.

Although not suggesting that U.S. taxpayers support the health care costs of undocumented aliens, the policy statement does recommend open access to comprehensive primary and preventive care – including vaccinations, prenatal and obstetrical care, and screening for preventable illness. Providing these services would not only reduce the cost burden associated with emergency room treatment when undocumented immigrants are acutely ill, it would help protect citizens who might be exposed to untreated, communicable disease, Dr. J. Fred Ralston Jr., immediate past president of the American College of Physicians, said at the group’s annual meeting

Tuberculosis is a case in point, he said at a press briefing. "Under the current system, [illegal immigrants] may be afraid that going to a hospital to seek treatment would place them at risk of deportation. If they delay care because of this fear, it could increase the number of people exposed to the diseases exponentially."

The 18-page paper is not a broad-based effort to address the overall problem of illegal immigration. Instead, Dr. Ralston said, it asks for a national policy that upholds the ethical responsibility of both physicians and the government to provide nondiscriminatory care to all people within U.S. borders.

"Any national immigration policy will need to balance the legitimate needs and concerns to control our borders and to equitably differentiate publicly supported services for those who fully comply with immigration laws and those who do not," he said. "However, access to health care for immigrants is crucial to the overall population of the U.S. We all have a vested interest in ensuring that all residents have access to necessary care."

The paper does not address the financial means by which such recommendations might be implemented. It does, however, stress that "[Immigrants without legal status] should not be prevented from paying out-of-pocket to cover their expenses, including the ability to purchase coverage at their own expense from the state health exchanges that will be created under the Affordable Care Act."

Further, Dr. Ralston, an internist in Fayetteville, Tenn., said that any national health policy should automatically cover native-born children of illegal aliens. "U.S.-born children of illegal residents should have the same access to purchased insurance and government-subsidized health care as any other U.S. citizen," according to the policy paper.

The college also unveiled recommendations for reforming Medicaid, focused on improving access to care for the millions who are, and will shortly become, eligible for its benefits.

‘The need for an improved Medicaid program was made evident during the recent recession, when almost 4 million people – the largest increase ever – found themselves relying on Medicaid for health care coverage," Dr. Ralston said. "Medicaid faces the potential of increasing enrollment of up to 18 million by 2019, with 10 states projecting a 50% increase."

But, he said, "With challenge comes the opportunity to improve Medicaid, with regard to its access and future sustainability."

The 38-page paper puts forth 12 recommendations, some of which concentrate on improving Medicaid payments to physicians. These, the paper says, are the foundations upon which a sound Medicaid program must be rebuilt. Among the paper’s recommendations:

• Standardize Medicaid minimum eligibility and fully subsidize federally mandated Medicaid coverage expansions. Without this, states will be forced to make up the gap, and patients will take the financial hit, said Robert B. Doherty, senior vice president of governmental affairs and public policy for the ACP;

• Offer more flexibility in long-term care choices, since alternatives can be less expensive than nursing homes;

• Streamline and improve the Medicaid waiver process, to ensure timely approval or rejection of waiver requests. Doing so may help ensure that more eligible patients enroll and take advantage of the program;

• Focus more on Medicaid programs that improve quality of care to minorities and effectively manage chronic disease and mental health disorders;

• Institute countercyclical funding to increase the amount of federal dollars available during economic downturns;

• Reduce enrollment barriers by state and federal cooperation. Such an effort would make enrollment easier and help ensure timely access to health care.

"The Medicaid system provides vital health services to vulnerable populations," Dr. Ralston said. "But like the health care system as a whole, Medicaid needs to be improved to emphasize preventive and primary care."

The paper calls for permanent Medicaid payment increases to primary care physicians and other specialist services, to at least the level of Medicare reimbursement

On the issue of anticipated budget cuts, Mr. Doherty added that the government should financially uphold programs to support physician recruitment and training, especially in light of expected primary care shortages. "Cutting programs to train more primary care providers would be penny-wise but pound-foolish. ... If Congress does not support these programs, we will face greater shortages, longer waits for appointments, and higher, budget-busting health care spending."

Dr. Ralston and Mr. Doherty reported having no disclosures.

SAN DIEGO – In two new position papers, the American College of Physicians declared support for both Medicaid reform and legislation that would provide broader health care access for immigrants – regardless of their legal status.

Although not suggesting that U.S. taxpayers support the health care costs of undocumented aliens, the policy statement does recommend open access to comprehensive primary and preventive care – including vaccinations, prenatal and obstetrical care, and screening for preventable illness. Providing these services would not only reduce the cost burden associated with emergency room treatment when undocumented immigrants are acutely ill, it would help protect citizens who might be exposed to untreated, communicable disease, Dr. J. Fred Ralston Jr., immediate past president of the American College of Physicians, said at the group’s annual meeting

Tuberculosis is a case in point, he said at a press briefing. "Under the current system, [illegal immigrants] may be afraid that going to a hospital to seek treatment would place them at risk of deportation. If they delay care because of this fear, it could increase the number of people exposed to the diseases exponentially."

The 18-page paper is not a broad-based effort to address the overall problem of illegal immigration. Instead, Dr. Ralston said, it asks for a national policy that upholds the ethical responsibility of both physicians and the government to provide nondiscriminatory care to all people within U.S. borders.

"Any national immigration policy will need to balance the legitimate needs and concerns to control our borders and to equitably differentiate publicly supported services for those who fully comply with immigration laws and those who do not," he said. "However, access to health care for immigrants is crucial to the overall population of the U.S. We all have a vested interest in ensuring that all residents have access to necessary care."

The paper does not address the financial means by which such recommendations might be implemented. It does, however, stress that "[Immigrants without legal status] should not be prevented from paying out-of-pocket to cover their expenses, including the ability to purchase coverage at their own expense from the state health exchanges that will be created under the Affordable Care Act."

Further, Dr. Ralston, an internist in Fayetteville, Tenn., said that any national health policy should automatically cover native-born children of illegal aliens. "U.S.-born children of illegal residents should have the same access to purchased insurance and government-subsidized health care as any other U.S. citizen," according to the policy paper.

The college also unveiled recommendations for reforming Medicaid, focused on improving access to care for the millions who are, and will shortly become, eligible for its benefits.

‘The need for an improved Medicaid program was made evident during the recent recession, when almost 4 million people – the largest increase ever – found themselves relying on Medicaid for health care coverage," Dr. Ralston said. "Medicaid faces the potential of increasing enrollment of up to 18 million by 2019, with 10 states projecting a 50% increase."

But, he said, "With challenge comes the opportunity to improve Medicaid, with regard to its access and future sustainability."

The 38-page paper puts forth 12 recommendations, some of which concentrate on improving Medicaid payments to physicians. These, the paper says, are the foundations upon which a sound Medicaid program must be rebuilt. Among the paper’s recommendations:

• Standardize Medicaid minimum eligibility and fully subsidize federally mandated Medicaid coverage expansions. Without this, states will be forced to make up the gap, and patients will take the financial hit, said Robert B. Doherty, senior vice president of governmental affairs and public policy for the ACP;

• Offer more flexibility in long-term care choices, since alternatives can be less expensive than nursing homes;

• Streamline and improve the Medicaid waiver process, to ensure timely approval or rejection of waiver requests. Doing so may help ensure that more eligible patients enroll and take advantage of the program;

• Focus more on Medicaid programs that improve quality of care to minorities and effectively manage chronic disease and mental health disorders;

• Institute countercyclical funding to increase the amount of federal dollars available during economic downturns;

• Reduce enrollment barriers by state and federal cooperation. Such an effort would make enrollment easier and help ensure timely access to health care.

"The Medicaid system provides vital health services to vulnerable populations," Dr. Ralston said. "But like the health care system as a whole, Medicaid needs to be improved to emphasize preventive and primary care."

The paper calls for permanent Medicaid payment increases to primary care physicians and other specialist services, to at least the level of Medicare reimbursement

On the issue of anticipated budget cuts, Mr. Doherty added that the government should financially uphold programs to support physician recruitment and training, especially in light of expected primary care shortages. "Cutting programs to train more primary care providers would be penny-wise but pound-foolish. ... If Congress does not support these programs, we will face greater shortages, longer waits for appointments, and higher, budget-busting health care spending."

Dr. Ralston and Mr. Doherty reported having no disclosures.

A minimally invasive esophagectomy resulted in improved postoperative outcomes and just as many resection rates (R0) as open surgery – with the added bonus of a significantly greater harvest of lymph nodes.

Compared with those who had open surgery, patients who underwent the minimally invasive surgery had significantly less blood loss, shorter hospital stays, and fewer major complications, said Dr. Adam C. Berger, who presented the study results at the recent annual meeting of the Southern Surgical Association.

Although further studies are needed to confirm the benefits of such an approach, "Our current practice is to attempt minimally invasive esophagectomies in all patients," said Dr. Berger of the Kimmel Cancer Center at the Thomas Jefferson University Hospital in Philadelphia.

He and his colleagues presented a retrospective study comparing surgical and oncologic outcomes in two groups of patients with esophageal cancer. His database comprised 65 patients who underwent esophagectomy with a thoracoscopic component (11 thoracoscopy/laparotomy, 2 Ivor-Lewis thoracoscopy/laparoscopy, and 52 three-hole thoracoscopy/laparoscopy). These were compared with a control group of 53 patients who underwent open surgery (15 Ivor-Lewis and 38 three-hole esophagectomy) during the same time period.

The patients’ mean age was 61 years. Neoadjuvant therapy was administered in 28 (43%) of the minimally invasive esophagectomy (MIE) group and 43 (81%) of the open surgery group.

Adenocarcinoma was present in most of the patients (85% MIE and 74% open). Squamous cell carcinoma occurred in 6% of the MIE group and 26% of the open group; there were also five cases (8%) of high-grade dysplasia in the MIE group. One patient had MIE for esophageal melanoma.

Dr. Berger briefly described his MIE approach. During the thoracoscopy, he uses 10-mm ports in the anterior axillary line at the fourth and eighth intercostal spaces and at the posterior axillary line. "A 5-mm port is placed at the tip of the scapula, and a suction port can be placed between the ports in the anterior axillary line," he said. "Finally, a suture is placed in the tendinous portion of the diaphragm to maintain retraction."

He uses a Penrose drain to encircle and retract the esophagus. The azygous vein is divided, and the aortic branches are divided or clipped. "The subcarinal lymph node package is dissected under direct vision and removed, and paraesophageal lymph nodes and tissue dissected up with the specimen."

During the subsequent laparoscopy, Dr. Berger places a 5-mm port in the right lateral subcostal area to accommodate a liver retractor, a 12-mm port in the umbilicus for the camera, an additional 12-mm working port in the right subcostal region, and a 5-mm port in the left subcostal region. "Once the gastric mobilization is complete, we often enlarge the 12-mm right subcostal port to about 5 cm and place a Lap Disk."

After dissecting the neck, he isolates and divides the esophagus. The completed reconstruction involves sewing the tip of the gastric tube to the chest tube and pulling that tube back up into the neck for a side-to-side esophagectomy. Anastomosis is in the neck with the gastric tube in the posterior mediastinum.

Mortality was similar in both groups of patients (8%). While the overall rate of complications was not significantly different (48% MIE vs. 60% open), the rate of major complications was (20% vs. 41%). Respiratory failure or acute respiratory distress syndrome occurred in a significantly smaller percentage of MIE patients (8% vs. 21%). There were also fewer cases of pneumonia among the MIE patients, but this was not a significant difference (8% vs. 18%). "Interestingly, there was a significant increase in the number of patients with a deep venous thrombosis or pulmonary embolism in the open group (2% vs. 11%)," Dr. Berger said. "This may have something to do with earlier postoperative mobilization for patients with MIE."

MIE patients also fared significantly better in terms of blood loss (182 mL vs. 619 mL) and median length of stay (9 vs. 16 days).

Oncologic outcomes were as good as, or better than, those seen in open surgery "There was no difference in R0 resection rates," Dr. Berger pointed out (97% MIE vs. 94% open). "We also saw a more than doubling of the number of examined lymph nodes in the MIE group, which was highly significant (20 vs. 9; P less than .0001)."

Despite the positive outcomes, Dr. Berger pointed out a major limitation of the study. Because his group attempts the MIE approach in all patients, "It’s impossible to find a concurrent group of patients who had open surgery for comparison." Also, he noted, "Pathology standards have changed and, thus, the importance of lymph nodes has become more recognized. Higher node yields are shown to be an important prognostic factor for survival. Therefore, our pathologists are now more diligent in finding the lymph nodes in the specimen."

Dr. Berger said he had no financial declarations.

A minimally invasive esophagectomy resulted in improved postoperative outcomes and just as many resection rates (R0) as open surgery – with the added bonus of a significantly greater harvest of lymph nodes.

Compared with those who had open surgery, patients who underwent the minimally invasive surgery had significantly less blood loss, shorter hospital stays, and fewer major complications, said Dr. Adam C. Berger, who presented the study results at the recent annual meeting of the Southern Surgical Association.

Although further studies are needed to confirm the benefits of such an approach, "Our current practice is to attempt minimally invasive esophagectomies in all patients," said Dr. Berger of the Kimmel Cancer Center at the Thomas Jefferson University Hospital in Philadelphia.

He and his colleagues presented a retrospective study comparing surgical and oncologic outcomes in two groups of patients with esophageal cancer. His database comprised 65 patients who underwent esophagectomy with a thoracoscopic component (11 thoracoscopy/laparotomy, 2 Ivor-Lewis thoracoscopy/laparoscopy, and 52 three-hole thoracoscopy/laparoscopy). These were compared with a control group of 53 patients who underwent open surgery (15 Ivor-Lewis and 38 three-hole esophagectomy) during the same time period.

The patients’ mean age was 61 years. Neoadjuvant therapy was administered in 28 (43%) of the minimally invasive esophagectomy (MIE) group and 43 (81%) of the open surgery group.

Adenocarcinoma was present in most of the patients (85% MIE and 74% open). Squamous cell carcinoma occurred in 6% of the MIE group and 26% of the open group; there were also five cases (8%) of high-grade dysplasia in the MIE group. One patient had MIE for esophageal melanoma.

Dr. Berger briefly described his MIE approach. During the thoracoscopy, he uses 10-mm ports in the anterior axillary line at the fourth and eighth intercostal spaces and at the posterior axillary line. "A 5-mm port is placed at the tip of the scapula, and a suction port can be placed between the ports in the anterior axillary line," he said. "Finally, a suture is placed in the tendinous portion of the diaphragm to maintain retraction."

He uses a Penrose drain to encircle and retract the esophagus. The azygous vein is divided, and the aortic branches are divided or clipped. "The subcarinal lymph node package is dissected under direct vision and removed, and paraesophageal lymph nodes and tissue dissected up with the specimen."

During the subsequent laparoscopy, Dr. Berger places a 5-mm port in the right lateral subcostal area to accommodate a liver retractor, a 12-mm port in the umbilicus for the camera, an additional 12-mm working port in the right subcostal region, and a 5-mm port in the left subcostal region. "Once the gastric mobilization is complete, we often enlarge the 12-mm right subcostal port to about 5 cm and place a Lap Disk."

After dissecting the neck, he isolates and divides the esophagus. The completed reconstruction involves sewing the tip of the gastric tube to the chest tube and pulling that tube back up into the neck for a side-to-side esophagectomy. Anastomosis is in the neck with the gastric tube in the posterior mediastinum.

Mortality was similar in both groups of patients (8%). While the overall rate of complications was not significantly different (48% MIE vs. 60% open), the rate of major complications was (20% vs. 41%). Respiratory failure or acute respiratory distress syndrome occurred in a significantly smaller percentage of MIE patients (8% vs. 21%). There were also fewer cases of pneumonia among the MIE patients, but this was not a significant difference (8% vs. 18%). "Interestingly, there was a significant increase in the number of patients with a deep venous thrombosis or pulmonary embolism in the open group (2% vs. 11%)," Dr. Berger said. "This may have something to do with earlier postoperative mobilization for patients with MIE."

MIE patients also fared significantly better in terms of blood loss (182 mL vs. 619 mL) and median length of stay (9 vs. 16 days).

Oncologic outcomes were as good as, or better than, those seen in open surgery "There was no difference in R0 resection rates," Dr. Berger pointed out (97% MIE vs. 94% open). "We also saw a more than doubling of the number of examined lymph nodes in the MIE group, which was highly significant (20 vs. 9; P less than .0001)."

Despite the positive outcomes, Dr. Berger pointed out a major limitation of the study. Because his group attempts the MIE approach in all patients, "It’s impossible to find a concurrent group of patients who had open surgery for comparison." Also, he noted, "Pathology standards have changed and, thus, the importance of lymph nodes has become more recognized. Higher node yields are shown to be an important prognostic factor for survival. Therefore, our pathologists are now more diligent in finding the lymph nodes in the specimen."

Dr. Berger said he had no financial declarations.

A minimally invasive esophagectomy resulted in improved postoperative outcomes and just as many resection rates (R0) as open surgery – with the added bonus of a significantly greater harvest of lymph nodes.

Compared with those who had open surgery, patients who underwent the minimally invasive surgery had significantly less blood loss, shorter hospital stays, and fewer major complications, said Dr. Adam C. Berger, who presented the study results at the recent annual meeting of the Southern Surgical Association.

Although further studies are needed to confirm the benefits of such an approach, "Our current practice is to attempt minimally invasive esophagectomies in all patients," said Dr. Berger of the Kimmel Cancer Center at the Thomas Jefferson University Hospital in Philadelphia.

He and his colleagues presented a retrospective study comparing surgical and oncologic outcomes in two groups of patients with esophageal cancer. His database comprised 65 patients who underwent esophagectomy with a thoracoscopic component (11 thoracoscopy/laparotomy, 2 Ivor-Lewis thoracoscopy/laparoscopy, and 52 three-hole thoracoscopy/laparoscopy). These were compared with a control group of 53 patients who underwent open surgery (15 Ivor-Lewis and 38 three-hole esophagectomy) during the same time period.

The patients’ mean age was 61 years. Neoadjuvant therapy was administered in 28 (43%) of the minimally invasive esophagectomy (MIE) group and 43 (81%) of the open surgery group.

Adenocarcinoma was present in most of the patients (85% MIE and 74% open). Squamous cell carcinoma occurred in 6% of the MIE group and 26% of the open group; there were also five cases (8%) of high-grade dysplasia in the MIE group. One patient had MIE for esophageal melanoma.

Dr. Berger briefly described his MIE approach. During the thoracoscopy, he uses 10-mm ports in the anterior axillary line at the fourth and eighth intercostal spaces and at the posterior axillary line. "A 5-mm port is placed at the tip of the scapula, and a suction port can be placed between the ports in the anterior axillary line," he said. "Finally, a suture is placed in the tendinous portion of the diaphragm to maintain retraction."

He uses a Penrose drain to encircle and retract the esophagus. The azygous vein is divided, and the aortic branches are divided or clipped. "The subcarinal lymph node package is dissected under direct vision and removed, and paraesophageal lymph nodes and tissue dissected up with the specimen."

During the subsequent laparoscopy, Dr. Berger places a 5-mm port in the right lateral subcostal area to accommodate a liver retractor, a 12-mm port in the umbilicus for the camera, an additional 12-mm working port in the right subcostal region, and a 5-mm port in the left subcostal region. "Once the gastric mobilization is complete, we often enlarge the 12-mm right subcostal port to about 5 cm and place a Lap Disk."

After dissecting the neck, he isolates and divides the esophagus. The completed reconstruction involves sewing the tip of the gastric tube to the chest tube and pulling that tube back up into the neck for a side-to-side esophagectomy. Anastomosis is in the neck with the gastric tube in the posterior mediastinum.

Mortality was similar in both groups of patients (8%). While the overall rate of complications was not significantly different (48% MIE vs. 60% open), the rate of major complications was (20% vs. 41%). Respiratory failure or acute respiratory distress syndrome occurred in a significantly smaller percentage of MIE patients (8% vs. 21%). There were also fewer cases of pneumonia among the MIE patients, but this was not a significant difference (8% vs. 18%). "Interestingly, there was a significant increase in the number of patients with a deep venous thrombosis or pulmonary embolism in the open group (2% vs. 11%)," Dr. Berger said. "This may have something to do with earlier postoperative mobilization for patients with MIE."

MIE patients also fared significantly better in terms of blood loss (182 mL vs. 619 mL) and median length of stay (9 vs. 16 days).

Oncologic outcomes were as good as, or better than, those seen in open surgery "There was no difference in R0 resection rates," Dr. Berger pointed out (97% MIE vs. 94% open). "We also saw a more than doubling of the number of examined lymph nodes in the MIE group, which was highly significant (20 vs. 9; P less than .0001)."

Despite the positive outcomes, Dr. Berger pointed out a major limitation of the study. Because his group attempts the MIE approach in all patients, "It’s impossible to find a concurrent group of patients who had open surgery for comparison." Also, he noted, "Pathology standards have changed and, thus, the importance of lymph nodes has become more recognized. Higher node yields are shown to be an important prognostic factor for survival. Therefore, our pathologists are now more diligent in finding the lymph nodes in the specimen."

Dr. Berger said he had no financial declarations.

A minimally invasive esophagectomy resulted in improved postoperative outcomes and just as many resection rates (R0) as open surgery – with the added bonus of a significantly greater harvest of lymph nodes.

Compared with those who had open surgery, patients who underwent the minimally invasive surgery had significantly less blood loss, shorter hospital stays, and fewer major complications, said Dr. Adam C. Berger, who presented the study results at the recent annual meeting of the Southern Surgical Association.

Although further studies are needed to confirm the benefits of such an approach, "Our current practice is to attempt minimally invasive esophagectomies in all patients," said Dr. Berger of the Kimmel Cancer Center at the Thomas Jefferson University Hospital in Philadelphia.

He and his colleagues presented a retrospective study comparing surgical and oncologic outcomes in two groups of patients with esophageal cancer. His database comprised 65 patients who underwent esophagectomy with a thoracoscopic component (11 thoracoscopy/laparotomy, 2 Ivor-Lewis thoracoscopy/laparoscopy, and 52 three-hole thoracoscopy/laparoscopy). These were compared with a control group of 53 patients who underwent open surgery (15 Ivor-Lewis and 38 three-hole esophagectomy) during the same time period.

The patients’ mean age was 61 years. Neoadjuvant therapy was administered in 28 (43%) of the minimally invasive esophagectomy (MIE) group and 43 (81%) of the open surgery group.

Adenocarcinoma was present in most of the patients (85% MIE and 74% open). Squamous cell carcinoma occurred in 6% of the MIE group and 26% of the open group; there were also five cases (8%) of high-grade dysplasia in the MIE group. One patient had MIE for esophageal melanoma.

Dr. Berger briefly described his MIE approach. During the thoracoscopy, he uses 10-mm ports in the anterior axillary line at the fourth and eighth intercostal spaces and at the posterior axillary line. "A 5-mm port is placed at the tip of the scapula, and a suction port can be placed between the ports in the anterior axillary line," he said. "Finally, a suture is placed in the tendinous portion of the diaphragm to maintain retraction."

He uses a Penrose drain to encircle and retract the esophagus. The azygous vein is divided, and the aortic branches are divided or clipped. "The subcarinal lymph node package is dissected under direct vision and removed, and paraesophageal lymph nodes and tissue dissected up with the specimen."

During the subsequent laparoscopy, Dr. Berger places a 5-mm port in the right lateral subcostal area to accommodate a liver retractor, a 12-mm port in the umbilicus for the camera, an additional 12-mm working port in the right subcostal region, and a 5-mm port in the left subcostal region. "Once the gastric mobilization is complete, we often enlarge the 12-mm right subcostal port to about 5 cm and place a Lap Disk."

After dissecting the neck, he isolates and divides the esophagus. The completed reconstruction involves sewing the tip of the gastric tube to the chest tube and pulling that tube back up into the neck for a side-to-side esophagectomy. Anastomosis is in the neck with the gastric tube in the posterior mediastinum.

Mortality was similar in both groups of patients (8%). While the overall rate of complications was not significantly different (48% MIE vs. 60% open), the rate of major complications was (20% vs. 41%). Respiratory failure or acute respiratory distress syndrome occurred in a significantly smaller percentage of MIE patients (8% vs. 21%). There were also fewer cases of pneumonia among the MIE patients, but this was not a significant difference (8% vs. 18%). "Interestingly, there was a significant increase in the number of patients with a deep venous thrombosis or pulmonary embolism in the open group (2% vs. 11%)," Dr. Berger said. "This may have something to do with earlier postoperative mobilization for patients with MIE."

MIE patients also fared significantly better in terms of blood loss (182 mL vs. 619 mL) and median length of stay (9 vs. 16 days).

Oncologic outcomes were as good as, or better than, those seen in open surgery "There was no difference in R0 resection rates," Dr. Berger pointed out (97% MIE vs. 94% open). "We also saw a more than doubling of the number of examined lymph nodes in the MIE group, which was highly significant (20 vs. 9; P less than .0001)."

Despite the positive outcomes, Dr. Berger pointed out a major limitation of the study. Because his group attempts the MIE approach in all patients, "It’s impossible to find a concurrent group of patients who had open surgery for comparison." Also, he noted, "Pathology standards have changed and, thus, the importance of lymph nodes has become more recognized. Higher node yields are shown to be an important prognostic factor for survival. Therefore, our pathologists are now more diligent in finding the lymph nodes in the specimen."

Dr. Berger said he had no financial declarations.

A minimally invasive esophagectomy resulted in improved postoperative outcomes and just as many resection rates (R0) as open surgery – with the added bonus of a significantly greater harvest of lymph nodes.

Compared with those who had open surgery, patients who underwent the minimally invasive surgery had significantly less blood loss, shorter hospital stays, and fewer major complications, said Dr. Adam C. Berger, who presented the study results at the recent annual meeting of the Southern Surgical Association.

Although further studies are needed to confirm the benefits of such an approach, "Our current practice is to attempt minimally invasive esophagectomies in all patients," said Dr. Berger of the Kimmel Cancer Center at the Thomas Jefferson University Hospital in Philadelphia.

He and his colleagues presented a retrospective study comparing surgical and oncologic outcomes in two groups of patients with esophageal cancer. His database comprised 65 patients who underwent esophagectomy with a thoracoscopic component (11 thoracoscopy/laparotomy, 2 Ivor-Lewis thoracoscopy/laparoscopy, and 52 three-hole thoracoscopy/laparoscopy). These were compared with a control group of 53 patients who underwent open surgery (15 Ivor-Lewis and 38 three-hole esophagectomy) during the same time period.

The patients’ mean age was 61 years. Neoadjuvant therapy was administered in 28 (43%) of the minimally invasive esophagectomy (MIE) group and 43 (81%) of the open surgery group.

Adenocarcinoma was present in most of the patients (85% MIE and 74% open). Squamous cell carcinoma occurred in 6% of the MIE group and 26% of the open group; there were also five cases (8%) of high-grade dysplasia in the MIE group. One patient had MIE for esophageal melanoma.

Dr. Berger briefly described his MIE approach. During the thoracoscopy, he uses 10-mm ports in the anterior axillary line at the fourth and eighth intercostal spaces and at the posterior axillary line. "A 5-mm port is placed at the tip of the scapula, and a suction port can be placed between the ports in the anterior axillary line," he said. "Finally, a suture is placed in the tendinous portion of the diaphragm to maintain retraction."

He uses a Penrose drain to encircle and retract the esophagus. The azygous vein is divided, and the aortic branches are divided or clipped. "The subcarinal lymph node package is dissected under direct vision and removed, and paraesophageal lymph nodes and tissue dissected up with the specimen."

During the subsequent laparoscopy, Dr. Berger places a 5-mm port in the right lateral subcostal area to accommodate a liver retractor, a 12-mm port in the umbilicus for the camera, an additional 12-mm working port in the right subcostal region, and a 5-mm port in the left subcostal region. "Once the gastric mobilization is complete, we often enlarge the 12-mm right subcostal port to about 5 cm and place a Lap Disk."

After dissecting the neck, he isolates and divides the esophagus. The completed reconstruction involves sewing the tip of the gastric tube to the chest tube and pulling that tube back up into the neck for a side-to-side esophagectomy. Anastomosis is in the neck with the gastric tube in the posterior mediastinum.

Mortality was similar in both groups of patients (8%). While the overall rate of complications was not significantly different (48% MIE vs. 60% open), the rate of major complications was (20% vs. 41%). Respiratory failure or acute respiratory distress syndrome occurred in a significantly smaller percentage of MIE patients (8% vs. 21%). There were also fewer cases of pneumonia among the MIE patients, but this was not a significant difference (8% vs. 18%). "Interestingly, there was a significant increase in the number of patients with a deep venous thrombosis or pulmonary embolism in the open group (2% vs. 11%)," Dr. Berger said. "This may have something to do with earlier postoperative mobilization for patients with MIE."

MIE patients also fared significantly better in terms of blood loss (182 mL vs. 619 mL) and median length of stay (9 vs. 16 days).

Oncologic outcomes were as good as, or better than, those seen in open surgery "There was no difference in R0 resection rates," Dr. Berger pointed out (97% MIE vs. 94% open). "We also saw a more than doubling of the number of examined lymph nodes in the MIE group, which was highly significant (20 vs. 9; P less than .0001)."

Despite the positive outcomes, Dr. Berger pointed out a major limitation of the study. Because his group attempts the MIE approach in all patients, "It’s impossible to find a concurrent group of patients who had open surgery for comparison." Also, he noted, "Pathology standards have changed and, thus, the importance of lymph nodes has become more recognized. Higher node yields are shown to be an important prognostic factor for survival. Therefore, our pathologists are now more diligent in finding the lymph nodes in the specimen."

Dr. Berger said he had no financial declarations.

A minimally invasive esophagectomy resulted in improved postoperative outcomes and just as many resection rates (R0) as open surgery – with the added bonus of a significantly greater harvest of lymph nodes.

Compared with those who had open surgery, patients who underwent the minimally invasive surgery had significantly less blood loss, shorter hospital stays, and fewer major complications, said Dr. Adam C. Berger, who presented the study results at the recent annual meeting of the Southern Surgical Association.

Although further studies are needed to confirm the benefits of such an approach, "Our current practice is to attempt minimally invasive esophagectomies in all patients," said Dr. Berger of the Kimmel Cancer Center at the Thomas Jefferson University Hospital in Philadelphia.

He and his colleagues presented a retrospective study comparing surgical and oncologic outcomes in two groups of patients with esophageal cancer. His database comprised 65 patients who underwent esophagectomy with a thoracoscopic component (11 thoracoscopy/laparotomy, 2 Ivor-Lewis thoracoscopy/laparoscopy, and 52 three-hole thoracoscopy/laparoscopy). These were compared with a control group of 53 patients who underwent open surgery (15 Ivor-Lewis and 38 three-hole esophagectomy) during the same time period.

The patients’ mean age was 61 years. Neoadjuvant therapy was administered in 28 (43%) of the minimally invasive esophagectomy (MIE) group and 43 (81%) of the open surgery group.

Adenocarcinoma was present in most of the patients (85% MIE and 74% open). Squamous cell carcinoma occurred in 6% of the MIE group and 26% of the open group; there were also five cases (8%) of high-grade dysplasia in the MIE group. One patient had MIE for esophageal melanoma.

Dr. Berger briefly described his MIE approach. During the thoracoscopy, he uses 10-mm ports in the anterior axillary line at the fourth and eighth intercostal spaces and at the posterior axillary line. "A 5-mm port is placed at the tip of the scapula, and a suction port can be placed between the ports in the anterior axillary line," he said. "Finally, a suture is placed in the tendinous portion of the diaphragm to maintain retraction."

He uses a Penrose drain to encircle and retract the esophagus. The azygous vein is divided, and the aortic branches are divided or clipped. "The subcarinal lymph node package is dissected under direct vision and removed, and paraesophageal lymph nodes and tissue dissected up with the specimen."

During the subsequent laparoscopy, Dr. Berger places a 5-mm port in the right lateral subcostal area to accommodate a liver retractor, a 12-mm port in the umbilicus for the camera, an additional 12-mm working port in the right subcostal region, and a 5-mm port in the left subcostal region. "Once the gastric mobilization is complete, we often enlarge the 12-mm right subcostal port to about 5 cm and place a Lap Disk."

After dissecting the neck, he isolates and divides the esophagus. The completed reconstruction involves sewing the tip of the gastric tube to the chest tube and pulling that tube back up into the neck for a side-to-side esophagectomy. Anastomosis is in the neck with the gastric tube in the posterior mediastinum.

Mortality was similar in both groups of patients (8%). While the overall rate of complications was not significantly different (48% MIE vs. 60% open), the rate of major complications was (20% vs. 41%). Respiratory failure or acute respiratory distress syndrome occurred in a significantly smaller percentage of MIE patients (8% vs. 21%). There were also fewer cases of pneumonia among the MIE patients, but this was not a significant difference (8% vs. 18%). "Interestingly, there was a significant increase in the number of patients with a deep venous thrombosis or pulmonary embolism in the open group (2% vs. 11%)," Dr. Berger said. "This may have something to do with earlier postoperative mobilization for patients with MIE."

MIE patients also fared significantly better in terms of blood loss (182 mL vs. 619 mL) and median length of stay (9 vs. 16 days).

Oncologic outcomes were as good as, or better than, those seen in open surgery "There was no difference in R0 resection rates," Dr. Berger pointed out (97% MIE vs. 94% open). "We also saw a more than doubling of the number of examined lymph nodes in the MIE group, which was highly significant (20 vs. 9; P less than .0001)."

Despite the positive outcomes, Dr. Berger pointed out a major limitation of the study. Because his group attempts the MIE approach in all patients, "It’s impossible to find a concurrent group of patients who had open surgery for comparison." Also, he noted, "Pathology standards have changed and, thus, the importance of lymph nodes has become more recognized. Higher node yields are shown to be an important prognostic factor for survival. Therefore, our pathologists are now more diligent in finding the lymph nodes in the specimen."

Dr. Berger said he had no financial declarations.

The Food and Drug Administration announced on Sept. 23 that it would preserve access to the controversial diabetes drug rosiglitazone, but only with what it called “significant restrictions.”

Under a risk evaluation and mitigation strategy (REMS), rosiglitazone will be available only to new patients with type 2 diabetes who are unable to adequately manage their blood glucose on pioglitazone or are unable to take pioglitazone, the only other approved thiazolidinedione.

However, patients who are already taking rosiglitazone may continue if, through the REMS program, they acknowledge their understanding of the drug’s potential cardiac risks, Dr. Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, said during a press briefing.

About 600,000 U.S. patients are taking the drug; Dr. Woodcock said the REMS program will “significantly reduce” that number, while ensuring that those who continue will fully understand its potential risk.

The European Medicines Agency, however, took a stronger stance on rosiglitazone, pulling it off the shelves in the European Union. Over the summer, EMA’s Committee for Medicinal Products for Human Use reviewed existing data and determined that rosiglitazone’s risks outweighed its benefits.

The FDA and EMA were aware of one another’s strategies but chose to handle the issue differently, Dr. Woodcock noted. “We heard very clearly from providers and patients that rosiglitazone is very effective for some patients who cannot tolerate other diabetes medications. We believe that this restricted use will enable health care providers and patients to be fully informed of the data and the concerns about the drug, and to make an informed decision if they want to remain on it.”

In a press statement, Dr. Ellen Strahlman, GlaxoSmithKline’s chief medical officer, said, “Our primary concern continues to be patients with type 2 diabetes, and we are making every effort to ensure that physicians in Europe and the U.S. have all the information they need to help them understand how these regulatory decisions affect them and their patients.”

The statement noted that “the company continues to believe that [rosiglitazone] is an important treatment for patients with type 2 diabetes and is now working with the FDA and EMA to implement the required actions … GSK will voluntarily cease promotion of [rosiglitazone] in all the countries in which it operates and will continue to respond to requests for information and support from healthcare professionals and patients.”

Rosiglitazone has been dogged for years by conflicting data on its cardiovascular safety profile. The recent RECORD trial, sponsored by the drug’s manufacturer, GlaxoSmithKline, was intended to settle the matter once and for all. But its findings of no increased risk in heart attack, overall death, and cardiovascular death failed to sway the FDA’s decision to restrict rosiglitazone access.

“The signal [of increased risk] has not been completely refuted by any evidence, so we think it is prudent to restrict access, and make sure that those using and prescribing the medication are aware of the facts and make the choice in an informed manner,” Dr. Woodcock said.

It will be “several months” before the REMS program can be fully implemented, Dr. Joshua Sharfstein said during the briefing. Until then, “Patients who are taking rosiglitazone should continue to do so, and consult their physician to discuss the possibility of selecting another medication without this concern of cardiac ischemia,” said Dr. Sharfstein, the FDA’s principal deputy commissioner. “Once the REMS is in place, physicians will need to enroll patients before they can continue to receive the drug.”

When the REMS is active, Dr. Sharfstein reiterated, rosiglitazone will only be available to patients who cannot control their blood sugar on any other medication, and who are unable to take pioglitazone for medical reasons. “Doctors will have to document this, and also that they have discussed the risks of rosiglitazone in order for the patient to receive the drug.”

The decision to restrict access came on the heels of an ever-increasing debate about rosiglitazone’s cardiovascular safety. Several trials have come to conflicting conclusions about whether the drug increased the risk of heart attack; a highly touted 2007 meta-analysis of 42 studies concluded that it increased that risk by up to 43%, and the risk of cardiovascular death by up to 64% (N. Engl. J. Med. 2007;356:2457-71).

In a statement released immediately after the FDA decision, Dr. Steven Nissen, the author of the meta-analysis, said that both the FDA and EMA decisions will result in essentially the same outcome and predicted that rosiglitazone “will quickly become a rarely used therapy.”

“By severely restricting access to rosiglitazone, the FDA is ensuring that only a few individuals in America will continue to take this drug. Only those patients who have failed to respond to all other therapies will be eligible to receive it,” said Dr. Nissen, chairman of cardiovascular medicine at the Cleveland Clinic.

Researchers had hoped the RECORD study would set the rosiglitazone risk story straight. But in July, the FDA panel tasked with reviewing the drug’s safety questioned RECORD and its adjudication of cardiovascular events, Dr. Woodcock said. “RECORD was an open-label trial, and it was determined that we can’t rely on those results, even though they did not show a significantly increased risk of cardiac harm. Therefore, the questions raised by the meta-analysis have not really been answered. We still believe there is considerable uncertainty about the magnitude of the cardiovascular risk.”

The FDA will ask GlaxoSmithKline to conduct an independent review of RECORD’s adjudication at a patient record level in an effort, Dr. Sharfstein said, “to catch events that occurred but which might have not been properly referred to the adjudication committee.”

At the press briefing, Dr. Woodcock also announced the termination of the Thiazolidinedione Intervention with Vitamin D Evaluation (TIDE) study, also sponsored by GlaxoSmithKline. TIDE was designed to determine any difference in cardiovascular safety between rosiglitazone and pioglitazone. In July, the FDA put TIDE on a partial hold, allowing patient enrollment, but not treatment. Today, Dr. Woodcock said the readjudication of RECORD should provide the answers needed to make the best decision about rosiglitazone’s future.

About 30 other drugs already carry REMS programs, including three formulations of pioglitazone. Pioglitazone tablets; pioglitazone/metformin tablets; and extended-release pioglitazone/metformin tablets all require the dispensing of a medical guide along with the medication – the most common REMS plan.

But other REMS programs – including the one that will be established for rosiglitazone – are much more restrictive, such as the one for the antiepileptic vigabatrin. That REMS requires not only a medication guide, but a communication plan to ensure reporting of adverse events, elements to assure safe use, and a system to ensure that physicians, pharmacies, and patients who do not comply with the rules lose access to the drug.

The Food and Drug Administration announced on Sept. 23 that it would preserve access to the controversial diabetes drug rosiglitazone, but only with what it called “significant restrictions.”

Under a risk evaluation and mitigation strategy (REMS), rosiglitazone will be available only to new patients with type 2 diabetes who are unable to adequately manage their blood glucose on pioglitazone or are unable to take pioglitazone, the only other approved thiazolidinedione.

However, patients who are already taking rosiglitazone may continue if, through the REMS program, they acknowledge their understanding of the drug’s potential cardiac risks, Dr. Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, said during a press briefing.

About 600,000 U.S. patients are taking the drug; Dr. Woodcock said the REMS program will “significantly reduce” that number, while ensuring that those who continue will fully understand its potential risk.

The European Medicines Agency, however, took a stronger stance on rosiglitazone, pulling it off the shelves in the European Union. Over the summer, EMA’s Committee for Medicinal Products for Human Use reviewed existing data and determined that rosiglitazone’s risks outweighed its benefits.

The FDA and EMA were aware of one another’s strategies but chose to handle the issue differently, Dr. Woodcock noted. “We heard very clearly from providers and patients that rosiglitazone is very effective for some patients who cannot tolerate other diabetes medications. We believe that this restricted use will enable health care providers and patients to be fully informed of the data and the concerns about the drug, and to make an informed decision if they want to remain on it.”

In a press statement, Dr. Ellen Strahlman, GlaxoSmithKline’s chief medical officer, said, “Our primary concern continues to be patients with type 2 diabetes, and we are making every effort to ensure that physicians in Europe and the U.S. have all the information they need to help them understand how these regulatory decisions affect them and their patients.”

The statement noted that “the company continues to believe that [rosiglitazone] is an important treatment for patients with type 2 diabetes and is now working with the FDA and EMA to implement the required actions … GSK will voluntarily cease promotion of [rosiglitazone] in all the countries in which it operates and will continue to respond to requests for information and support from healthcare professionals and patients.”

Rosiglitazone has been dogged for years by conflicting data on its cardiovascular safety profile. The recent RECORD trial, sponsored by the drug’s manufacturer, GlaxoSmithKline, was intended to settle the matter once and for all. But its findings of no increased risk in heart attack, overall death, and cardiovascular death failed to sway the FDA’s decision to restrict rosiglitazone access.

“The signal [of increased risk] has not been completely refuted by any evidence, so we think it is prudent to restrict access, and make sure that those using and prescribing the medication are aware of the facts and make the choice in an informed manner,” Dr. Woodcock said.

It will be “several months” before the REMS program can be fully implemented, Dr. Joshua Sharfstein said during the briefing. Until then, “Patients who are taking rosiglitazone should continue to do so, and consult their physician to discuss the possibility of selecting another medication without this concern of cardiac ischemia,” said Dr. Sharfstein, the FDA’s principal deputy commissioner. “Once the REMS is in place, physicians will need to enroll patients before they can continue to receive the drug.”

When the REMS is active, Dr. Sharfstein reiterated, rosiglitazone will only be available to patients who cannot control their blood sugar on any other medication, and who are unable to take pioglitazone for medical reasons. “Doctors will have to document this, and also that they have discussed the risks of rosiglitazone in order for the patient to receive the drug.”

The decision to restrict access came on the heels of an ever-increasing debate about rosiglitazone’s cardiovascular safety. Several trials have come to conflicting conclusions about whether the drug increased the risk of heart attack; a highly touted 2007 meta-analysis of 42 studies concluded that it increased that risk by up to 43%, and the risk of cardiovascular death by up to 64% (N. Engl. J. Med. 2007;356:2457-71).

In a statement released immediately after the FDA decision, Dr. Steven Nissen, the author of the meta-analysis, said that both the FDA and EMA decisions will result in essentially the same outcome and predicted that rosiglitazone “will quickly become a rarely used therapy.”

“By severely restricting access to rosiglitazone, the FDA is ensuring that only a few individuals in America will continue to take this drug. Only those patients who have failed to respond to all other therapies will be eligible to receive it,” said Dr. Nissen, chairman of cardiovascular medicine at the Cleveland Clinic.

Researchers had hoped the RECORD study would set the rosiglitazone risk story straight. But in July, the FDA panel tasked with reviewing the drug’s safety questioned RECORD and its adjudication of cardiovascular events, Dr. Woodcock said. “RECORD was an open-label trial, and it was determined that we can’t rely on those results, even though they did not show a significantly increased risk of cardiac harm. Therefore, the questions raised by the meta-analysis have not really been answered. We still believe there is considerable uncertainty about the magnitude of the cardiovascular risk.”

The FDA will ask GlaxoSmithKline to conduct an independent review of RECORD’s adjudication at a patient record level in an effort, Dr. Sharfstein said, “to catch events that occurred but which might have not been properly referred to the adjudication committee.”

At the press briefing, Dr. Woodcock also announced the termination of the Thiazolidinedione Intervention with Vitamin D Evaluation (TIDE) study, also sponsored by GlaxoSmithKline. TIDE was designed to determine any difference in cardiovascular safety between rosiglitazone and pioglitazone. In July, the FDA put TIDE on a partial hold, allowing patient enrollment, but not treatment. Today, Dr. Woodcock said the readjudication of RECORD should provide the answers needed to make the best decision about rosiglitazone’s future.

About 30 other drugs already carry REMS programs, including three formulations of pioglitazone. Pioglitazone tablets; pioglitazone/metformin tablets; and extended-release pioglitazone/metformin tablets all require the dispensing of a medical guide along with the medication – the most common REMS plan.

But other REMS programs – including the one that will be established for rosiglitazone – are much more restrictive, such as the one for the antiepileptic vigabatrin. That REMS requires not only a medication guide, but a communication plan to ensure reporting of adverse events, elements to assure safe use, and a system to ensure that physicians, pharmacies, and patients who do not comply with the rules lose access to the drug.

The Food and Drug Administration announced on Sept. 23 that it would preserve access to the controversial diabetes drug rosiglitazone, but only with what it called “significant restrictions.”

Under a risk evaluation and mitigation strategy (REMS), rosiglitazone will be available only to new patients with type 2 diabetes who are unable to adequately manage their blood glucose on pioglitazone or are unable to take pioglitazone, the only other approved thiazolidinedione.

However, patients who are already taking rosiglitazone may continue if, through the REMS program, they acknowledge their understanding of the drug’s potential cardiac risks, Dr. Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, said during a press briefing.

About 600,000 U.S. patients are taking the drug; Dr. Woodcock said the REMS program will “significantly reduce” that number, while ensuring that those who continue will fully understand its potential risk.

The European Medicines Agency, however, took a stronger stance on rosiglitazone, pulling it off the shelves in the European Union. Over the summer, EMA’s Committee for Medicinal Products for Human Use reviewed existing data and determined that rosiglitazone’s risks outweighed its benefits.

The FDA and EMA were aware of one another’s strategies but chose to handle the issue differently, Dr. Woodcock noted. “We heard very clearly from providers and patients that rosiglitazone is very effective for some patients who cannot tolerate other diabetes medications. We believe that this restricted use will enable health care providers and patients to be fully informed of the data and the concerns about the drug, and to make an informed decision if they want to remain on it.”

In a press statement, Dr. Ellen Strahlman, GlaxoSmithKline’s chief medical officer, said, “Our primary concern continues to be patients with type 2 diabetes, and we are making every effort to ensure that physicians in Europe and the U.S. have all the information they need to help them understand how these regulatory decisions affect them and their patients.”

The statement noted that “the company continues to believe that [rosiglitazone] is an important treatment for patients with type 2 diabetes and is now working with the FDA and EMA to implement the required actions … GSK will voluntarily cease promotion of [rosiglitazone] in all the countries in which it operates and will continue to respond to requests for information and support from healthcare professionals and patients.”

Rosiglitazone has been dogged for years by conflicting data on its cardiovascular safety profile. The recent RECORD trial, sponsored by the drug’s manufacturer, GlaxoSmithKline, was intended to settle the matter once and for all. But its findings of no increased risk in heart attack, overall death, and cardiovascular death failed to sway the FDA’s decision to restrict rosiglitazone access.

“The signal [of increased risk] has not been completely refuted by any evidence, so we think it is prudent to restrict access, and make sure that those using and prescribing the medication are aware of the facts and make the choice in an informed manner,” Dr. Woodcock said.

It will be “several months” before the REMS program can be fully implemented, Dr. Joshua Sharfstein said during the briefing. Until then, “Patients who are taking rosiglitazone should continue to do so, and consult their physician to discuss the possibility of selecting another medication without this concern of cardiac ischemia,” said Dr. Sharfstein, the FDA’s principal deputy commissioner. “Once the REMS is in place, physicians will need to enroll patients before they can continue to receive the drug.”

When the REMS is active, Dr. Sharfstein reiterated, rosiglitazone will only be available to patients who cannot control their blood sugar on any other medication, and who are unable to take pioglitazone for medical reasons. “Doctors will have to document this, and also that they have discussed the risks of rosiglitazone in order for the patient to receive the drug.”

The decision to restrict access came on the heels of an ever-increasing debate about rosiglitazone’s cardiovascular safety. Several trials have come to conflicting conclusions about whether the drug increased the risk of heart attack; a highly touted 2007 meta-analysis of 42 studies concluded that it increased that risk by up to 43%, and the risk of cardiovascular death by up to 64% (N. Engl. J. Med. 2007;356:2457-71).

In a statement released immediately after the FDA decision, Dr. Steven Nissen, the author of the meta-analysis, said that both the FDA and EMA decisions will result in essentially the same outcome and predicted that rosiglitazone “will quickly become a rarely used therapy.”

“By severely restricting access to rosiglitazone, the FDA is ensuring that only a few individuals in America will continue to take this drug. Only those patients who have failed to respond to all other therapies will be eligible to receive it,” said Dr. Nissen, chairman of cardiovascular medicine at the Cleveland Clinic.

Researchers had hoped the RECORD study would set the rosiglitazone risk story straight. But in July, the FDA panel tasked with reviewing the drug’s safety questioned RECORD and its adjudication of cardiovascular events, Dr. Woodcock said. “RECORD was an open-label trial, and it was determined that we can’t rely on those results, even though they did not show a significantly increased risk of cardiac harm. Therefore, the questions raised by the meta-analysis have not really been answered. We still believe there is considerable uncertainty about the magnitude of the cardiovascular risk.”

The FDA will ask GlaxoSmithKline to conduct an independent review of RECORD’s adjudication at a patient record level in an effort, Dr. Sharfstein said, “to catch events that occurred but which might have not been properly referred to the adjudication committee.”

At the press briefing, Dr. Woodcock also announced the termination of the Thiazolidinedione Intervention with Vitamin D Evaluation (TIDE) study, also sponsored by GlaxoSmithKline. TIDE was designed to determine any difference in cardiovascular safety between rosiglitazone and pioglitazone. In July, the FDA put TIDE on a partial hold, allowing patient enrollment, but not treatment. Today, Dr. Woodcock said the readjudication of RECORD should provide the answers needed to make the best decision about rosiglitazone’s future.

About 30 other drugs already carry REMS programs, including three formulations of pioglitazone. Pioglitazone tablets; pioglitazone/metformin tablets; and extended-release pioglitazone/metformin tablets all require the dispensing of a medical guide along with the medication – the most common REMS plan.

But other REMS programs – including the one that will be established for rosiglitazone – are much more restrictive, such as the one for the antiepileptic vigabatrin. That REMS requires not only a medication guide, but a communication plan to ensure reporting of adverse events, elements to assure safe use, and a system to ensure that physicians, pharmacies, and patients who do not comply with the rules lose access to the drug.