General Surgery

Current smoking is associated with an increased risk of mortality and other adverse outcomes following major surgery, but past smoking is not, according to a report published online June 19 in JAMA Surgery.

Current smoking correlates with these adverse outcomes even in patients who don’t have obvious smoking-related disease such cardiovascular disease, chronic pulmonary disorders, or cancer, which suggests that smoking may exert its deleterious effects through acute or subclinical chronic vascular and respiratory pathologic mechanisms, said Dr. Khaled M. Musallam of the American University of Beirut (Lebanon) Medical Center and his associates.

©thinkstockphotos.com

Current smoking is associated with an increased risk of mortality and other adverse outcomes following major surgery, but past smoking is not, according to a recent report published in JAMA Surgery.

Since smoking cessation has clear benefits on morbidity and mortality in the surgical setting, "surgical teams should be more involved in the ongoing efforts to optimize measures for smoking control," they wrote.

"Surgery provides a teachable environment for smoking cessation. Unlike the long-term consequences of smoking, the acute consequences of smoking on patients’ postoperative outcomes can provide a strong motive for quitting," the investigators said.

Dr. Musallam and his colleagues examined the effect of smoking on surgical outcomes using data from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP), which includes a registry that provides feedback to participating hospitals regarding 30-day risk-adjusted surgical morbidity and mortality.

For this study, they analyzed data on 607,558 patients undergoing major surgery at more than 200 participating hospitals during a 2-year period in the United States, Canada, Lebanon, and the United Arab Emirates. The mean age of the patients was 56 years (range, 16-90 years); 43% were men and 57% were women.

A total of 125,192 patients (21%) were current smokers and 78,763 (13%) were past smokers who had quit at least 1 year before surgery. The remaining patients had never smoked.

Only current smokers showed an increased likelihood of 30-day mortality. They also were at greater risk for adverse arterial events such as MI or stroke, as well as for adverse respiratory events such as pneumonia, need for intubation, and need for a ventilator, within 30 days of surgery, the investigators said (JAMA Surg. 2013 June 19 [doi:10.1001/jamasurg.2013.2360]).

The higher risk of these adverse outcomes occurred with smokers across all age groups but was particularly notable among those older than age 40 years. It was seen in both sexes, among those undergoing inpatient as well as outpatient procedures, in patients who had general as well as other types of anesthesia, across a variety of surgical subspecialties, and in both elective and emergency surgery cases.

The association between current smoking and adverse outcomes also remained robust in a sensitivity analysis, Dr. Musallam and his associates said.

There was a dose-response effect in an analysis of patients’ smoking history, with the likelihood of adverse arterial and respiratory events increasing in tandem with increasing pack-years of smoking, but even current "light" smokers who had fewer than 10 pack-years of smoking history were at increased risk for postoperative mortality and morbidity.

"These findings encourage ongoing efforts to implement smoking cessation programs," Dr. Musallam and his associates said.

"Early intervention in heavy smokers is warranted, especially because the effect of smoking on postoperative arterial and respiratory morbidity seems to be dose dependent. However, because smokers with a cigarette smoking history of less than 10 pack-years are also at risk of postoperative death, recent and light smokers should also be targeted," they suggested.

Dr. Musallam and his associates reported no financial conflicts of interest.

Current smoking is associated with an increased risk of mortality and other adverse outcomes following major surgery, but past smoking is not, according to a report published online June 19 in JAMA Surgery.

Current smoking correlates with these adverse outcomes even in patients who don’t have obvious smoking-related disease such cardiovascular disease, chronic pulmonary disorders, or cancer, which suggests that smoking may exert its deleterious effects through acute or subclinical chronic vascular and respiratory pathologic mechanisms, said Dr. Khaled M. Musallam of the American University of Beirut (Lebanon) Medical Center and his associates.

©thinkstockphotos.com

Current smoking is associated with an increased risk of mortality and other adverse outcomes following major surgery, but past smoking is not, according to a recent report published in JAMA Surgery.

Since smoking cessation has clear benefits on morbidity and mortality in the surgical setting, "surgical teams should be more involved in the ongoing efforts to optimize measures for smoking control," they wrote.

"Surgery provides a teachable environment for smoking cessation. Unlike the long-term consequences of smoking, the acute consequences of smoking on patients’ postoperative outcomes can provide a strong motive for quitting," the investigators said.

Dr. Musallam and his colleagues examined the effect of smoking on surgical outcomes using data from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP), which includes a registry that provides feedback to participating hospitals regarding 30-day risk-adjusted surgical morbidity and mortality.

For this study, they analyzed data on 607,558 patients undergoing major surgery at more than 200 participating hospitals during a 2-year period in the United States, Canada, Lebanon, and the United Arab Emirates. The mean age of the patients was 56 years (range, 16-90 years); 43% were men and 57% were women.

A total of 125,192 patients (21%) were current smokers and 78,763 (13%) were past smokers who had quit at least 1 year before surgery. The remaining patients had never smoked.

Only current smokers showed an increased likelihood of 30-day mortality. They also were at greater risk for adverse arterial events such as MI or stroke, as well as for adverse respiratory events such as pneumonia, need for intubation, and need for a ventilator, within 30 days of surgery, the investigators said (JAMA Surg. 2013 June 19 [doi:10.1001/jamasurg.2013.2360]).

The higher risk of these adverse outcomes occurred with smokers across all age groups but was particularly notable among those older than age 40 years. It was seen in both sexes, among those undergoing inpatient as well as outpatient procedures, in patients who had general as well as other types of anesthesia, across a variety of surgical subspecialties, and in both elective and emergency surgery cases.

The association between current smoking and adverse outcomes also remained robust in a sensitivity analysis, Dr. Musallam and his associates said.

There was a dose-response effect in an analysis of patients’ smoking history, with the likelihood of adverse arterial and respiratory events increasing in tandem with increasing pack-years of smoking, but even current "light" smokers who had fewer than 10 pack-years of smoking history were at increased risk for postoperative mortality and morbidity.

"These findings encourage ongoing efforts to implement smoking cessation programs," Dr. Musallam and his associates said.

"Early intervention in heavy smokers is warranted, especially because the effect of smoking on postoperative arterial and respiratory morbidity seems to be dose dependent. However, because smokers with a cigarette smoking history of less than 10 pack-years are also at risk of postoperative death, recent and light smokers should also be targeted," they suggested.

Dr. Musallam and his associates reported no financial conflicts of interest.

Current smoking is associated with an increased risk of mortality and other adverse outcomes following major surgery, but past smoking is not, according to a report published online June 19 in JAMA Surgery.

Current smoking correlates with these adverse outcomes even in patients who don’t have obvious smoking-related disease such cardiovascular disease, chronic pulmonary disorders, or cancer, which suggests that smoking may exert its deleterious effects through acute or subclinical chronic vascular and respiratory pathologic mechanisms, said Dr. Khaled M. Musallam of the American University of Beirut (Lebanon) Medical Center and his associates.

©thinkstockphotos.com

Current smoking is associated with an increased risk of mortality and other adverse outcomes following major surgery, but past smoking is not, according to a recent report published in JAMA Surgery.

Since smoking cessation has clear benefits on morbidity and mortality in the surgical setting, "surgical teams should be more involved in the ongoing efforts to optimize measures for smoking control," they wrote.

"Surgery provides a teachable environment for smoking cessation. Unlike the long-term consequences of smoking, the acute consequences of smoking on patients’ postoperative outcomes can provide a strong motive for quitting," the investigators said.

Dr. Musallam and his colleagues examined the effect of smoking on surgical outcomes using data from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP), which includes a registry that provides feedback to participating hospitals regarding 30-day risk-adjusted surgical morbidity and mortality.

For this study, they analyzed data on 607,558 patients undergoing major surgery at more than 200 participating hospitals during a 2-year period in the United States, Canada, Lebanon, and the United Arab Emirates. The mean age of the patients was 56 years (range, 16-90 years); 43% were men and 57% were women.

A total of 125,192 patients (21%) were current smokers and 78,763 (13%) were past smokers who had quit at least 1 year before surgery. The remaining patients had never smoked.

Only current smokers showed an increased likelihood of 30-day mortality. They also were at greater risk for adverse arterial events such as MI or stroke, as well as for adverse respiratory events such as pneumonia, need for intubation, and need for a ventilator, within 30 days of surgery, the investigators said (JAMA Surg. 2013 June 19 [doi:10.1001/jamasurg.2013.2360]).

The higher risk of these adverse outcomes occurred with smokers across all age groups but was particularly notable among those older than age 40 years. It was seen in both sexes, among those undergoing inpatient as well as outpatient procedures, in patients who had general as well as other types of anesthesia, across a variety of surgical subspecialties, and in both elective and emergency surgery cases.

The association between current smoking and adverse outcomes also remained robust in a sensitivity analysis, Dr. Musallam and his associates said.

There was a dose-response effect in an analysis of patients’ smoking history, with the likelihood of adverse arterial and respiratory events increasing in tandem with increasing pack-years of smoking, but even current "light" smokers who had fewer than 10 pack-years of smoking history were at increased risk for postoperative mortality and morbidity.

"These findings encourage ongoing efforts to implement smoking cessation programs," Dr. Musallam and his associates said.

"Early intervention in heavy smokers is warranted, especially because the effect of smoking on postoperative arterial and respiratory morbidity seems to be dose dependent. However, because smokers with a cigarette smoking history of less than 10 pack-years are also at risk of postoperative death, recent and light smokers should also be targeted," they suggested.

Dr. Musallam and his associates reported no financial conflicts of interest.

ORLANDO – In hepatocellular carcinoma, tumor size did not independently influence recurrence or survival, whereas tumor histopathology and background parenchyma did, according to a retrospective, single-center study of 300 patients.

"These findings further support that prognosis and treatment guidelines cannot be effectively categorized based on tumor size," said Dr. Michael D. Kluger of the department of surgery at New York-Presbyterian Hospital–Cornell University, New York.

Although the procedure is hampered by high recurrence rates, resection is safe, readily available, and offers good overall survival, he said.

Also, "This strategy can allow for the more effective utilization of a limited (and dwindling) supply of transplantable livers; freeing other patients from the potential short- and long-term complications of undergoing unnecessary transplantation," Dr. Kluger said.

Meanwhile, "many treatments with curative intent remain available after recurrence, including re-resection, salvage transplantation, and ablation," he said.

He presented his abstract, which is not published, during the annual Digestive Disease Week.

Dr. Kluger and his colleagues studied 313 patients with hepatocellular carcinoma (HCC) who underwent liver resection between 1989 and 2010.

Patients were stratified based on tumor size of less than 50 mm (36%), 50-100 mm (36%), and more than 100 mm (28%).

Patients with larger tumors were more likely to have normal liver parenchyma: 43% of patients with tumors larger than 100 mm, compared with 1% of patients with tumors smaller than 50 mm (P less than .001).

The influence of tumor size on overall survival was significant in univariate analyses (less than 50 mm vs. 50-100 mm, P = .0321; less then 50 mm vs. more than 100 mm, P = 0.009; 50-100 mm vs. more than 100 mm, P = .57), said Dr. Kluger, but when the salvage transplantation cases were excluded, tumor size was no longer significant (P = .18, .07, and .65, respectively.)

Researchers found seven independent predictors that led to decreased overall survival: intraoperative transfusion (hazard ratio, 2.60), cirrhosis (HR, 2.42), poorly differentiated tumor (HR, 2.04), satellite lesions (HR, 1.68), microvascular invasion (HR, 1.48), alpha-fetoprotein more than 200 ng/mL (HR, 1.53), and salvage transplantation (HR, 0.23).

Median overall survival was 60 months. One-year overall survival was 76%, and 5-year overall survival was 50%. Meanwhile, 5-year survival of patients who underwent salvage transplantation from the time of occurrence was 90%, compared with 18% for those not undergoing the procedure (P less than .0001).

The median time to recurrence was 20 months, with 1-year recurrence-free survival at 61%, and 5-year recurrence-free survival at 28%.

Four variables independently affected recurrence-free survival, the authors noted: intra-operative transfusion (HR, 2.15), poorly differentiated tumor (HR, 1.87), cirrhosis (HR, 1.69), and microvascular invasion (HR, 1.71).

Patients with nontransplantable recurrences after resection of tumors smaller than 5 cm had similar overall survival, compared with patients whose tumors were originally 5 cm or larger.

The study also showed that the rate of complications decreased during the second decade of the study period. While the mortality rate between 1989 and 1999 was 14%, it dropped to 5% through 2010 (P less than .008).

"These improvements coincide with major advances in liver surgery, patient selection, anesthetic practices, liver imaging, and postoperative care," said Dr. Kluger in an interview. "We also believe that routine integration of laparoscopy for appropriate cases since 1998 was also critical to improvements in outcomes. Whereas 6% of the cases performed prior to 2000 utilized a laparoscopic technique, 30% performed after 2000 did."

Dr. Kluger said that "tumor size is a widely accepted but inadequate proxy for interactions within the tumor milieu. ... The onus is to determine which patients would most benefit from upfront listing for transplantation despite candidacy for resection, or resection with the future possibility of salvage transplantation for recurrence," he said.

Dr. Kluger had no disclosures.

nmiller@frontlinemedcom.com

On Twitter @NaseemSMiller

ORLANDO – In hepatocellular carcinoma, tumor size did not independently influence recurrence or survival, whereas tumor histopathology and background parenchyma did, according to a retrospective, single-center study of 300 patients.

"These findings further support that prognosis and treatment guidelines cannot be effectively categorized based on tumor size," said Dr. Michael D. Kluger of the department of surgery at New York-Presbyterian Hospital–Cornell University, New York.

Although the procedure is hampered by high recurrence rates, resection is safe, readily available, and offers good overall survival, he said.

Also, "This strategy can allow for the more effective utilization of a limited (and dwindling) supply of transplantable livers; freeing other patients from the potential short- and long-term complications of undergoing unnecessary transplantation," Dr. Kluger said.

Meanwhile, "many treatments with curative intent remain available after recurrence, including re-resection, salvage transplantation, and ablation," he said.

He presented his abstract, which is not published, during the annual Digestive Disease Week.

Dr. Kluger and his colleagues studied 313 patients with hepatocellular carcinoma (HCC) who underwent liver resection between 1989 and 2010.

Patients were stratified based on tumor size of less than 50 mm (36%), 50-100 mm (36%), and more than 100 mm (28%).

Patients with larger tumors were more likely to have normal liver parenchyma: 43% of patients with tumors larger than 100 mm, compared with 1% of patients with tumors smaller than 50 mm (P less than .001).

The influence of tumor size on overall survival was significant in univariate analyses (less than 50 mm vs. 50-100 mm, P = .0321; less then 50 mm vs. more than 100 mm, P = 0.009; 50-100 mm vs. more than 100 mm, P = .57), said Dr. Kluger, but when the salvage transplantation cases were excluded, tumor size was no longer significant (P = .18, .07, and .65, respectively.)

Researchers found seven independent predictors that led to decreased overall survival: intraoperative transfusion (hazard ratio, 2.60), cirrhosis (HR, 2.42), poorly differentiated tumor (HR, 2.04), satellite lesions (HR, 1.68), microvascular invasion (HR, 1.48), alpha-fetoprotein more than 200 ng/mL (HR, 1.53), and salvage transplantation (HR, 0.23).

Median overall survival was 60 months. One-year overall survival was 76%, and 5-year overall survival was 50%. Meanwhile, 5-year survival of patients who underwent salvage transplantation from the time of occurrence was 90%, compared with 18% for those not undergoing the procedure (P less than .0001).

The median time to recurrence was 20 months, with 1-year recurrence-free survival at 61%, and 5-year recurrence-free survival at 28%.

Four variables independently affected recurrence-free survival, the authors noted: intra-operative transfusion (HR, 2.15), poorly differentiated tumor (HR, 1.87), cirrhosis (HR, 1.69), and microvascular invasion (HR, 1.71).

Patients with nontransplantable recurrences after resection of tumors smaller than 5 cm had similar overall survival, compared with patients whose tumors were originally 5 cm or larger.

The study also showed that the rate of complications decreased during the second decade of the study period. While the mortality rate between 1989 and 1999 was 14%, it dropped to 5% through 2010 (P less than .008).

"These improvements coincide with major advances in liver surgery, patient selection, anesthetic practices, liver imaging, and postoperative care," said Dr. Kluger in an interview. "We also believe that routine integration of laparoscopy for appropriate cases since 1998 was also critical to improvements in outcomes. Whereas 6% of the cases performed prior to 2000 utilized a laparoscopic technique, 30% performed after 2000 did."

Dr. Kluger said that "tumor size is a widely accepted but inadequate proxy for interactions within the tumor milieu. ... The onus is to determine which patients would most benefit from upfront listing for transplantation despite candidacy for resection, or resection with the future possibility of salvage transplantation for recurrence," he said.

Dr. Kluger had no disclosures.

nmiller@frontlinemedcom.com

On Twitter @NaseemSMiller

ORLANDO – In hepatocellular carcinoma, tumor size did not independently influence recurrence or survival, whereas tumor histopathology and background parenchyma did, according to a retrospective, single-center study of 300 patients.

"These findings further support that prognosis and treatment guidelines cannot be effectively categorized based on tumor size," said Dr. Michael D. Kluger of the department of surgery at New York-Presbyterian Hospital–Cornell University, New York.

Although the procedure is hampered by high recurrence rates, resection is safe, readily available, and offers good overall survival, he said.

Also, "This strategy can allow for the more effective utilization of a limited (and dwindling) supply of transplantable livers; freeing other patients from the potential short- and long-term complications of undergoing unnecessary transplantation," Dr. Kluger said.

Meanwhile, "many treatments with curative intent remain available after recurrence, including re-resection, salvage transplantation, and ablation," he said.

He presented his abstract, which is not published, during the annual Digestive Disease Week.

Dr. Kluger and his colleagues studied 313 patients with hepatocellular carcinoma (HCC) who underwent liver resection between 1989 and 2010.

Patients were stratified based on tumor size of less than 50 mm (36%), 50-100 mm (36%), and more than 100 mm (28%).

Patients with larger tumors were more likely to have normal liver parenchyma: 43% of patients with tumors larger than 100 mm, compared with 1% of patients with tumors smaller than 50 mm (P less than .001).

The influence of tumor size on overall survival was significant in univariate analyses (less than 50 mm vs. 50-100 mm, P = .0321; less then 50 mm vs. more than 100 mm, P = 0.009; 50-100 mm vs. more than 100 mm, P = .57), said Dr. Kluger, but when the salvage transplantation cases were excluded, tumor size was no longer significant (P = .18, .07, and .65, respectively.)

Researchers found seven independent predictors that led to decreased overall survival: intraoperative transfusion (hazard ratio, 2.60), cirrhosis (HR, 2.42), poorly differentiated tumor (HR, 2.04), satellite lesions (HR, 1.68), microvascular invasion (HR, 1.48), alpha-fetoprotein more than 200 ng/mL (HR, 1.53), and salvage transplantation (HR, 0.23).

Median overall survival was 60 months. One-year overall survival was 76%, and 5-year overall survival was 50%. Meanwhile, 5-year survival of patients who underwent salvage transplantation from the time of occurrence was 90%, compared with 18% for those not undergoing the procedure (P less than .0001).

The median time to recurrence was 20 months, with 1-year recurrence-free survival at 61%, and 5-year recurrence-free survival at 28%.

Four variables independently affected recurrence-free survival, the authors noted: intra-operative transfusion (HR, 2.15), poorly differentiated tumor (HR, 1.87), cirrhosis (HR, 1.69), and microvascular invasion (HR, 1.71).

Patients with nontransplantable recurrences after resection of tumors smaller than 5 cm had similar overall survival, compared with patients whose tumors were originally 5 cm or larger.

The study also showed that the rate of complications decreased during the second decade of the study period. While the mortality rate between 1989 and 1999 was 14%, it dropped to 5% through 2010 (P less than .008).

"These improvements coincide with major advances in liver surgery, patient selection, anesthetic practices, liver imaging, and postoperative care," said Dr. Kluger in an interview. "We also believe that routine integration of laparoscopy for appropriate cases since 1998 was also critical to improvements in outcomes. Whereas 6% of the cases performed prior to 2000 utilized a laparoscopic technique, 30% performed after 2000 did."

Dr. Kluger said that "tumor size is a widely accepted but inadequate proxy for interactions within the tumor milieu. ... The onus is to determine which patients would most benefit from upfront listing for transplantation despite candidacy for resection, or resection with the future possibility of salvage transplantation for recurrence," he said.

Dr. Kluger had no disclosures.

nmiller@frontlinemedcom.com

On Twitter @NaseemSMiller

Blood glucose levels should be targeted to 140-200 mg/dL in surgical or medical ICU patients on insulin therapy, according to advice the American College of Physicians published online May 24 in the American Journal of Medical Quality.

Also, "clinicians should avoid targets less than ... 140 mg/dL because harms are likely to increase with lower blood glucose targets," the group said (Am. J. Med. Qual. 2013 [doi: 10.1177/1062860613489339]).

The advice isn’t new, but instead a restatement of ACP’s 2011 inpatient glycemic control guidelines reissued as part of its "Best Practice Advice" campaign, said Paul G. Shekelle, Ph.D., senior author of both the advice paper and guidelines (Ann. Intern. Med. 2011;154:260-7).

"This is based on the prior guidelines, so there’s nothing new here in that sense. The Best Practice Advice series sometimes runs in parallel to the guidelines, sometimes it is something completely different than any ACP guidelines, and sometimes, like this case, it runs asynchronous to the guidelines. Ideally, these will be more synchronous in the future," Dr. Shekelle, director of the RAND Corporation’s Southern California Evidence-Based Practice Center, said in an interview.

ACP’s advice is largely in keeping with glucose control recommendations from other groups, which have tended toward liberalization in recent years amid evidence that aggressive, euglycemic control in hospitalized patients, even if they have diabetes, doesn’t improve outcomes and carries too high a risk of hypoglycemia and its attendant problems.

"Nobody is advocating tight glycemic control anymore in the hospital. It isn’t necessary and may be harmful," said Dr. Etie S. Moghissi, the lead author on a 2009 inpatient glycemic control consensus statement issued by the American Association of Clinical Endocrinologists and American Diabetes Association (Diabetes Care 2009;32:1119-31).

The consensus statement recommended an upper limit of 180 mg/dL based on the pivotal NICE-SUGAR study, instead of 200 mg/dL, which Dr. Shekelle said ACP chose because it was the upper target limit in several of the additional studies upon which the group based its 2011 guidelines (N. Engl. .J Med. 2009;360:1283-97).

But Dr. Moghissi, who is with the department of medicine at the University of California, Los Angeles, said she’s concerned that 200 mg/dL might be too high.

"We know that when we set targets, people do not achieve them. So when we set a higher target, most of the time people go above that. The concern" is that a target of 200 mg/dL "may be perceived [as meaning that] a little bit over 200 mg/dL is okay," but "above 200 mg/dL, usually there are issues with increased risk of infection, poor wound healing, volume depletion," and other problems, she said in an interview.

Dr. Shekelle and Dr. Moghissi said they have no relevant disclosures.

aotto@frontlinemedcom.com

Blood glucose levels should be targeted to 140-200 mg/dL in surgical or medical ICU patients on insulin therapy, according to advice the American College of Physicians published online May 24 in the American Journal of Medical Quality.

Also, "clinicians should avoid targets less than ... 140 mg/dL because harms are likely to increase with lower blood glucose targets," the group said (Am. J. Med. Qual. 2013 [doi: 10.1177/1062860613489339]).

The advice isn’t new, but instead a restatement of ACP’s 2011 inpatient glycemic control guidelines reissued as part of its "Best Practice Advice" campaign, said Paul G. Shekelle, Ph.D., senior author of both the advice paper and guidelines (Ann. Intern. Med. 2011;154:260-7).

"This is based on the prior guidelines, so there’s nothing new here in that sense. The Best Practice Advice series sometimes runs in parallel to the guidelines, sometimes it is something completely different than any ACP guidelines, and sometimes, like this case, it runs asynchronous to the guidelines. Ideally, these will be more synchronous in the future," Dr. Shekelle, director of the RAND Corporation’s Southern California Evidence-Based Practice Center, said in an interview.

ACP’s advice is largely in keeping with glucose control recommendations from other groups, which have tended toward liberalization in recent years amid evidence that aggressive, euglycemic control in hospitalized patients, even if they have diabetes, doesn’t improve outcomes and carries too high a risk of hypoglycemia and its attendant problems.

"Nobody is advocating tight glycemic control anymore in the hospital. It isn’t necessary and may be harmful," said Dr. Etie S. Moghissi, the lead author on a 2009 inpatient glycemic control consensus statement issued by the American Association of Clinical Endocrinologists and American Diabetes Association (Diabetes Care 2009;32:1119-31).

The consensus statement recommended an upper limit of 180 mg/dL based on the pivotal NICE-SUGAR study, instead of 200 mg/dL, which Dr. Shekelle said ACP chose because it was the upper target limit in several of the additional studies upon which the group based its 2011 guidelines (N. Engl. .J Med. 2009;360:1283-97).

But Dr. Moghissi, who is with the department of medicine at the University of California, Los Angeles, said she’s concerned that 200 mg/dL might be too high.

"We know that when we set targets, people do not achieve them. So when we set a higher target, most of the time people go above that. The concern" is that a target of 200 mg/dL "may be perceived [as meaning that] a little bit over 200 mg/dL is okay," but "above 200 mg/dL, usually there are issues with increased risk of infection, poor wound healing, volume depletion," and other problems, she said in an interview.

Dr. Shekelle and Dr. Moghissi said they have no relevant disclosures.

aotto@frontlinemedcom.com

Blood glucose levels should be targeted to 140-200 mg/dL in surgical or medical ICU patients on insulin therapy, according to advice the American College of Physicians published online May 24 in the American Journal of Medical Quality.

Also, "clinicians should avoid targets less than ... 140 mg/dL because harms are likely to increase with lower blood glucose targets," the group said (Am. J. Med. Qual. 2013 [doi: 10.1177/1062860613489339]).

The advice isn’t new, but instead a restatement of ACP’s 2011 inpatient glycemic control guidelines reissued as part of its "Best Practice Advice" campaign, said Paul G. Shekelle, Ph.D., senior author of both the advice paper and guidelines (Ann. Intern. Med. 2011;154:260-7).

"This is based on the prior guidelines, so there’s nothing new here in that sense. The Best Practice Advice series sometimes runs in parallel to the guidelines, sometimes it is something completely different than any ACP guidelines, and sometimes, like this case, it runs asynchronous to the guidelines. Ideally, these will be more synchronous in the future," Dr. Shekelle, director of the RAND Corporation’s Southern California Evidence-Based Practice Center, said in an interview.

ACP’s advice is largely in keeping with glucose control recommendations from other groups, which have tended toward liberalization in recent years amid evidence that aggressive, euglycemic control in hospitalized patients, even if they have diabetes, doesn’t improve outcomes and carries too high a risk of hypoglycemia and its attendant problems.

"Nobody is advocating tight glycemic control anymore in the hospital. It isn’t necessary and may be harmful," said Dr. Etie S. Moghissi, the lead author on a 2009 inpatient glycemic control consensus statement issued by the American Association of Clinical Endocrinologists and American Diabetes Association (Diabetes Care 2009;32:1119-31).

The consensus statement recommended an upper limit of 180 mg/dL based on the pivotal NICE-SUGAR study, instead of 200 mg/dL, which Dr. Shekelle said ACP chose because it was the upper target limit in several of the additional studies upon which the group based its 2011 guidelines (N. Engl. .J Med. 2009;360:1283-97).

But Dr. Moghissi, who is with the department of medicine at the University of California, Los Angeles, said she’s concerned that 200 mg/dL might be too high.

"We know that when we set targets, people do not achieve them. So when we set a higher target, most of the time people go above that. The concern" is that a target of 200 mg/dL "may be perceived [as meaning that] a little bit over 200 mg/dL is okay," but "above 200 mg/dL, usually there are issues with increased risk of infection, poor wound healing, volume depletion," and other problems, she said in an interview.

Dr. Shekelle and Dr. Moghissi said they have no relevant disclosures.

aotto@frontlinemedcom.com

ORLANDO – Thromboprophylaxis for 3 weeks after discharge following abdominal surgery is more cost effective than is inpatient thromboprophylaxis alone, given certain base case assumptions, according to a decision tree analysis.

The findings, which incorporate both cost- and patient-related factors, provide clarity for clinicians about when extended duration thromboprophylaxis is appropriate, Dr. James C. Iannuzzi said at the annual Digestive Disease Week.

The analysis indicates that extended-duration thromboprophylaxis with low-molecular-weight heparin for 3 weeks after discharge is preferable to 7 days of inpatient-only thromboprophylaxis in cases where venous thromboembolism (VTE) risk is estimated at 0.88% to 2.39%; patient preferences regarding costs and medication administration, including the need for self-administered injection of low-molecular-weight heparin (LMWH), should be considered in these cases, said Dr. Iannuzzi of surgical health outcomes and research enterprise at the University of Rochester (N.Y.) Medical Center.

Extended-duration thromboprophylaxis dominates in cases in which the estimated VTE risk exceeds 2.39%, he said.

"Current guidelines are inconsistent about what metrics should be used, which makes it difficult for providers to decide whether extended-duration thromboprophylaxis would be beneficial. This likely plays a significant role in the current lack of adherence to guidelines," he said in an interview, adding. "This study was really aimed at providing clinicians a better cut-off for when it should be used, incorporating both the cost and patient perspective."

To assess cost effectiveness of thromboprophylaxis, Dr. Iannuzzi and his colleagues compared extended-duration treatment for 21 days after discharge (following 7 days of inpatient prophylaxis) with inpatient prophylaxis alone in a hypothetical case involving abdominal oncologic resection without complications in an otherwise healthy 45-year-old male patient.

Willingness to pay was set at $50,000 per quality-adjusted life-year (QALY), and the probabilities of various factors and scenarios were determined based on the available literature – much of it coming from the orthopedic literature. Costs were in U.S. 2013 dollars adjusted using the consumer price index; effectiveness was based on QALY (utility considered over 1 year), and cost effectiveness was evaluated using an incremental cost-effectiveness ratio, Dr. Iannuzzi explained.

Sensitivity analyses were performed to assess uncertainty within the model, with particular interest in the threshold for cost effectiveness based on VTE incidence, he said.

The endpoints were pulmonary embolism or deep vein thrombosis with attendant costs and assigned effectiveness evaluated by QALY, he said.

Based on the predetermined probabilities, and assuming an annualized cost of $23,248 for pulmonary embolism, $21,540 for deep vein thrombosis, $14,363 for post-thrombotic syndrome, $706 for generic LMWH, and $872 for brand-name LMWH, the threshold for the relative cost effectiveness of extended-duration thromboprophylaxis was VTE probability of 1.65% for brand-name LMWH, and 0.88% for generic LMWH.

"The 0.88% threshold is near the range of most major abdominal surgeries, which highlights the importance of using extended-duration thromboprophylaxis. However, the model was sensitive to changes in medication costs and patient values until postdischarge VTE risk exceeded 2.4%," Dr. Iannuzzi explained, adding that the model sensitivity in the 0.88% to 2.39% range is the reason why it is important to consider the patient perspective and the availability of generic LWMH in such cases.

He and his colleagues recently developed a risk score to help with postdischarge VTE prediction and to guide decision-making. The risk score, published online in May in the Journal of Vascular Surgery (J. Vasc. Surg. 2013 [doi:10.106/j.jvs.2012.12.073]), considers patient, operative, and early outcome factors to identify patients at increased risk.

The current findings, which pave the way for patient-centered decision making, use cost effectiveness of extended-duration thromboprophylaxis as a measure for risk, and should inform future guidelines’ definition of high risk. They also suggest that while a blanket approach to prophylaxis is not warranted, payers should cover the cost of extended-duration treatment.

"When cost was analyzed alone – without taking patient discomfort and the burden of self-injections into account, the threshold for cost effectiveness was much lower, suggesting that from the payer perspective, significant cost savings would be derived by increasing extended-duration thromboprophylaxis use," he explained.

Dr. Iannuzzi reported having no disclosures.

ORLANDO – Thromboprophylaxis for 3 weeks after discharge following abdominal surgery is more cost effective than is inpatient thromboprophylaxis alone, given certain base case assumptions, according to a decision tree analysis.

The findings, which incorporate both cost- and patient-related factors, provide clarity for clinicians about when extended duration thromboprophylaxis is appropriate, Dr. James C. Iannuzzi said at the annual Digestive Disease Week.

The analysis indicates that extended-duration thromboprophylaxis with low-molecular-weight heparin for 3 weeks after discharge is preferable to 7 days of inpatient-only thromboprophylaxis in cases where venous thromboembolism (VTE) risk is estimated at 0.88% to 2.39%; patient preferences regarding costs and medication administration, including the need for self-administered injection of low-molecular-weight heparin (LMWH), should be considered in these cases, said Dr. Iannuzzi of surgical health outcomes and research enterprise at the University of Rochester (N.Y.) Medical Center.

Extended-duration thromboprophylaxis dominates in cases in which the estimated VTE risk exceeds 2.39%, he said.

"Current guidelines are inconsistent about what metrics should be used, which makes it difficult for providers to decide whether extended-duration thromboprophylaxis would be beneficial. This likely plays a significant role in the current lack of adherence to guidelines," he said in an interview, adding. "This study was really aimed at providing clinicians a better cut-off for when it should be used, incorporating both the cost and patient perspective."

To assess cost effectiveness of thromboprophylaxis, Dr. Iannuzzi and his colleagues compared extended-duration treatment for 21 days after discharge (following 7 days of inpatient prophylaxis) with inpatient prophylaxis alone in a hypothetical case involving abdominal oncologic resection without complications in an otherwise healthy 45-year-old male patient.

Willingness to pay was set at $50,000 per quality-adjusted life-year (QALY), and the probabilities of various factors and scenarios were determined based on the available literature – much of it coming from the orthopedic literature. Costs were in U.S. 2013 dollars adjusted using the consumer price index; effectiveness was based on QALY (utility considered over 1 year), and cost effectiveness was evaluated using an incremental cost-effectiveness ratio, Dr. Iannuzzi explained.

Sensitivity analyses were performed to assess uncertainty within the model, with particular interest in the threshold for cost effectiveness based on VTE incidence, he said.

The endpoints were pulmonary embolism or deep vein thrombosis with attendant costs and assigned effectiveness evaluated by QALY, he said.

Based on the predetermined probabilities, and assuming an annualized cost of $23,248 for pulmonary embolism, $21,540 for deep vein thrombosis, $14,363 for post-thrombotic syndrome, $706 for generic LMWH, and $872 for brand-name LMWH, the threshold for the relative cost effectiveness of extended-duration thromboprophylaxis was VTE probability of 1.65% for brand-name LMWH, and 0.88% for generic LMWH.

"The 0.88% threshold is near the range of most major abdominal surgeries, which highlights the importance of using extended-duration thromboprophylaxis. However, the model was sensitive to changes in medication costs and patient values until postdischarge VTE risk exceeded 2.4%," Dr. Iannuzzi explained, adding that the model sensitivity in the 0.88% to 2.39% range is the reason why it is important to consider the patient perspective and the availability of generic LWMH in such cases.

He and his colleagues recently developed a risk score to help with postdischarge VTE prediction and to guide decision-making. The risk score, published online in May in the Journal of Vascular Surgery (J. Vasc. Surg. 2013 [doi:10.106/j.jvs.2012.12.073]), considers patient, operative, and early outcome factors to identify patients at increased risk.

The current findings, which pave the way for patient-centered decision making, use cost effectiveness of extended-duration thromboprophylaxis as a measure for risk, and should inform future guidelines’ definition of high risk. They also suggest that while a blanket approach to prophylaxis is not warranted, payers should cover the cost of extended-duration treatment.

"When cost was analyzed alone – without taking patient discomfort and the burden of self-injections into account, the threshold for cost effectiveness was much lower, suggesting that from the payer perspective, significant cost savings would be derived by increasing extended-duration thromboprophylaxis use," he explained.

Dr. Iannuzzi reported having no disclosures.

ORLANDO – Thromboprophylaxis for 3 weeks after discharge following abdominal surgery is more cost effective than is inpatient thromboprophylaxis alone, given certain base case assumptions, according to a decision tree analysis.

The findings, which incorporate both cost- and patient-related factors, provide clarity for clinicians about when extended duration thromboprophylaxis is appropriate, Dr. James C. Iannuzzi said at the annual Digestive Disease Week.

The analysis indicates that extended-duration thromboprophylaxis with low-molecular-weight heparin for 3 weeks after discharge is preferable to 7 days of inpatient-only thromboprophylaxis in cases where venous thromboembolism (VTE) risk is estimated at 0.88% to 2.39%; patient preferences regarding costs and medication administration, including the need for self-administered injection of low-molecular-weight heparin (LMWH), should be considered in these cases, said Dr. Iannuzzi of surgical health outcomes and research enterprise at the University of Rochester (N.Y.) Medical Center.

Extended-duration thromboprophylaxis dominates in cases in which the estimated VTE risk exceeds 2.39%, he said.

"Current guidelines are inconsistent about what metrics should be used, which makes it difficult for providers to decide whether extended-duration thromboprophylaxis would be beneficial. This likely plays a significant role in the current lack of adherence to guidelines," he said in an interview, adding. "This study was really aimed at providing clinicians a better cut-off for when it should be used, incorporating both the cost and patient perspective."

To assess cost effectiveness of thromboprophylaxis, Dr. Iannuzzi and his colleagues compared extended-duration treatment for 21 days after discharge (following 7 days of inpatient prophylaxis) with inpatient prophylaxis alone in a hypothetical case involving abdominal oncologic resection without complications in an otherwise healthy 45-year-old male patient.

Willingness to pay was set at $50,000 per quality-adjusted life-year (QALY), and the probabilities of various factors and scenarios were determined based on the available literature – much of it coming from the orthopedic literature. Costs were in U.S. 2013 dollars adjusted using the consumer price index; effectiveness was based on QALY (utility considered over 1 year), and cost effectiveness was evaluated using an incremental cost-effectiveness ratio, Dr. Iannuzzi explained.

Sensitivity analyses were performed to assess uncertainty within the model, with particular interest in the threshold for cost effectiveness based on VTE incidence, he said.

The endpoints were pulmonary embolism or deep vein thrombosis with attendant costs and assigned effectiveness evaluated by QALY, he said.

Based on the predetermined probabilities, and assuming an annualized cost of $23,248 for pulmonary embolism, $21,540 for deep vein thrombosis, $14,363 for post-thrombotic syndrome, $706 for generic LMWH, and $872 for brand-name LMWH, the threshold for the relative cost effectiveness of extended-duration thromboprophylaxis was VTE probability of 1.65% for brand-name LMWH, and 0.88% for generic LMWH.

"The 0.88% threshold is near the range of most major abdominal surgeries, which highlights the importance of using extended-duration thromboprophylaxis. However, the model was sensitive to changes in medication costs and patient values until postdischarge VTE risk exceeded 2.4%," Dr. Iannuzzi explained, adding that the model sensitivity in the 0.88% to 2.39% range is the reason why it is important to consider the patient perspective and the availability of generic LWMH in such cases.

He and his colleagues recently developed a risk score to help with postdischarge VTE prediction and to guide decision-making. The risk score, published online in May in the Journal of Vascular Surgery (J. Vasc. Surg. 2013 [doi:10.106/j.jvs.2012.12.073]), considers patient, operative, and early outcome factors to identify patients at increased risk.

The current findings, which pave the way for patient-centered decision making, use cost effectiveness of extended-duration thromboprophylaxis as a measure for risk, and should inform future guidelines’ definition of high risk. They also suggest that while a blanket approach to prophylaxis is not warranted, payers should cover the cost of extended-duration treatment.

"When cost was analyzed alone – without taking patient discomfort and the burden of self-injections into account, the threshold for cost effectiveness was much lower, suggesting that from the payer perspective, significant cost savings would be derived by increasing extended-duration thromboprophylaxis use," he explained.

Dr. Iannuzzi reported having no disclosures.

ORLANDO – Although obesity is more prevalent among blacks, fewer get bariatric surgery, and for those who do, the outcomes are less efficacious than for whites and Hispanics, according to analysis of a national database, examining the influence of ethnicity on bariatric surgery.

"All qualified obese patients, particularly the rapidly growing black population, need improved access to bariatric surgery to reduce mortality," said Dr. Ranjan Sudan, vice chair of education in the department of surgery at Duke University, Durham, N.C. He presented his unpublished abstract at the annual Digestive Disease Week.

Studies have shown that bariatric surgery is an effective treatment for obesity and decreases mortality, but the reason behind the disparity and surgery outcomes is rather nuanced and not so clear (N. Engl. J. Med. 2007;357:753-61).

A 2012 study at the Louisiana State University System, Baton Rouge, found that white females appeared to lose more weight than did black females regardless of the type of bariatric surgery, although both races experienced surgical complications. Also, "black patients may be less likely to undergo bariatric surgery without insurance coverage," the authors wrote (Adv. Ther. 2012;29:970-8).

Meanwhile, a 2012 meta-analysis looking at ethnic differences in weight loss and diabetes remission after bariatric surgery found that for the percentage of excess weight loss, bariatric surgery was more effective in whites than in blacks, regardless of procedure type. "Further studies are needed to investigate the exact mechanisms behind these disparities and to determine whether ethnic differences exist in the remission of comorbidities after bariatric surgery," the authors wrote (Diabetes Care 2012;35:1951-8).

"It could be because of underlying difference in physiology among races," an area that is still poorly-understood, Dr. Vic Velanovich, professor of medicine at the University of South Florida, Tampa, said in an interview. Also, "Is this a problem of geographic variation?" he said, commenting on Dr. Sudan’s findings. "Are blacks getting their health care in such a way that they don’t have access to bariatric surgery? And the third issue is cultural. It could be very well that [the] cultural view of body image is different. So there are a lot of unanswered questions," said Dr. Velanovich, who was not involved in the study.

Dr. Sudan and his colleagues examined the primary Roux-en-Y gastric bypass surgery (RYGB) data from the American Society for Bariatric and Metabolic Surgery database, submitted by more than 1,000 surgeons and 700 hospitals between June 2007 and September 2011.

All patients gave research consent and were eligible for 1-year follow-up.

Of the 135,000 patients, 79% were white, 12% black, and 9% Hispanic. Compared with whites at baseline, black patients were younger (43 years vs. 46 years), heavier (body mass index of 50 kg/m² vs. 48 kg/m²), and were more often hypertensive (58% vs. 53%).

Among black patients who were undergoing RYGB, 15% were male, compared with 23% white and 22% Hispanic males. More black patients had a history of hypertension (57%), compared with whites (52%) and Hispanics (41%). Hispanic patients had the least comorbid disease burden, said Dr. Sudan.

Meanwhile, more white patients had diabetes (32%), compared with Hispanics (31%) and blacks (30%), at baseline.

Follow up rates were 60% in white patients, 50% in Hispanics, and 49% in blacks.

Overall, the benefits of RYGB were significant in the three groups at 1-year follow-up, but the procedure was less efficient for black patients, according to the analysis.

For instance, although fewer black patients had diabetes at baseline, at 1-year follow-up a higher percentage of them had diabetes with less decline in diabetes rates (from 30% to 13%, decline of 59%), compared with whites (from 32% to 11%; –65%), and Hispanics (from 31% to 12%; –61%.)

Black patients also had less decline in the mean body mass index (–30%), compared with whites (–34%), and Hispanics (–32%). Their hypertension also declined less (–35%) than in whites (–49%), and Hispanics (–50%).

The mortality rates within 30 days were similar for all three group (0.23%-0.26%), but black patients had a higher rate of total adverse events (22%), compared with whites and Hispanics (17% each).

The study has some limitations, said Dr. Sudan. Some of the data is self-reported, and researchers did not stratify disease severity by ethnicity.

Recent studies shows that grade 2 or higher obesity (BMI of 35 or more) is most prevalent among blacks (26%), compared with whites (15%) and Hispanics (15%). The overall rate for all ethnicities is 15.5%. (JAMA 2012;307:491-7). Black women also have the highest rate of grade 2 or higher obesity (31%), followed by black men (21%), Hispanic women (18%), white women (17%), white men (12%), and Hispanic men (11.4%).

Dr. Sudan also pointed out that the black population has higher rates of hypertension and diabetes, compared with Hispanics and whites, while more white patients (56%) control their hypertension, compared with blacks (48%) and Hispanics (41%) (NCHS Data Brief 2012;107:1-8).

"Hypertension control is very important because hypertension is a risk factor for cardiovascular mortality," said Dr. Sudan. "If the medical control is not good, then we certainly want to consider bariatric surgery."

Dr. Sudan said the he’s planning on examining the database for geographic distribution and socioeconomic factors.

Dr. Sudan and Dr. Velanovich said they had no disclosures.

nmiller@frontlinemedcom.com

On Twitter @NaseemSMiller

ORLANDO – Although obesity is more prevalent among blacks, fewer get bariatric surgery, and for those who do, the outcomes are less efficacious than for whites and Hispanics, according to analysis of a national database, examining the influence of ethnicity on bariatric surgery.

"All qualified obese patients, particularly the rapidly growing black population, need improved access to bariatric surgery to reduce mortality," said Dr. Ranjan Sudan, vice chair of education in the department of surgery at Duke University, Durham, N.C. He presented his unpublished abstract at the annual Digestive Disease Week.

Studies have shown that bariatric surgery is an effective treatment for obesity and decreases mortality, but the reason behind the disparity and surgery outcomes is rather nuanced and not so clear (N. Engl. J. Med. 2007;357:753-61).

A 2012 study at the Louisiana State University System, Baton Rouge, found that white females appeared to lose more weight than did black females regardless of the type of bariatric surgery, although both races experienced surgical complications. Also, "black patients may be less likely to undergo bariatric surgery without insurance coverage," the authors wrote (Adv. Ther. 2012;29:970-8).

Meanwhile, a 2012 meta-analysis looking at ethnic differences in weight loss and diabetes remission after bariatric surgery found that for the percentage of excess weight loss, bariatric surgery was more effective in whites than in blacks, regardless of procedure type. "Further studies are needed to investigate the exact mechanisms behind these disparities and to determine whether ethnic differences exist in the remission of comorbidities after bariatric surgery," the authors wrote (Diabetes Care 2012;35:1951-8).

"It could be because of underlying difference in physiology among races," an area that is still poorly-understood, Dr. Vic Velanovich, professor of medicine at the University of South Florida, Tampa, said in an interview. Also, "Is this a problem of geographic variation?" he said, commenting on Dr. Sudan’s findings. "Are blacks getting their health care in such a way that they don’t have access to bariatric surgery? And the third issue is cultural. It could be very well that [the] cultural view of body image is different. So there are a lot of unanswered questions," said Dr. Velanovich, who was not involved in the study.

Dr. Sudan and his colleagues examined the primary Roux-en-Y gastric bypass surgery (RYGB) data from the American Society for Bariatric and Metabolic Surgery database, submitted by more than 1,000 surgeons and 700 hospitals between June 2007 and September 2011.

All patients gave research consent and were eligible for 1-year follow-up.

Of the 135,000 patients, 79% were white, 12% black, and 9% Hispanic. Compared with whites at baseline, black patients were younger (43 years vs. 46 years), heavier (body mass index of 50 kg/m² vs. 48 kg/m²), and were more often hypertensive (58% vs. 53%).

Among black patients who were undergoing RYGB, 15% were male, compared with 23% white and 22% Hispanic males. More black patients had a history of hypertension (57%), compared with whites (52%) and Hispanics (41%). Hispanic patients had the least comorbid disease burden, said Dr. Sudan.

Meanwhile, more white patients had diabetes (32%), compared with Hispanics (31%) and blacks (30%), at baseline.

Follow up rates were 60% in white patients, 50% in Hispanics, and 49% in blacks.

Overall, the benefits of RYGB were significant in the three groups at 1-year follow-up, but the procedure was less efficient for black patients, according to the analysis.

For instance, although fewer black patients had diabetes at baseline, at 1-year follow-up a higher percentage of them had diabetes with less decline in diabetes rates (from 30% to 13%, decline of 59%), compared with whites (from 32% to 11%; –65%), and Hispanics (from 31% to 12%; –61%.)

Black patients also had less decline in the mean body mass index (–30%), compared with whites (–34%), and Hispanics (–32%). Their hypertension also declined less (–35%) than in whites (–49%), and Hispanics (–50%).

The mortality rates within 30 days were similar for all three group (0.23%-0.26%), but black patients had a higher rate of total adverse events (22%), compared with whites and Hispanics (17% each).

The study has some limitations, said Dr. Sudan. Some of the data is self-reported, and researchers did not stratify disease severity by ethnicity.

Recent studies shows that grade 2 or higher obesity (BMI of 35 or more) is most prevalent among blacks (26%), compared with whites (15%) and Hispanics (15%). The overall rate for all ethnicities is 15.5%. (JAMA 2012;307:491-7). Black women also have the highest rate of grade 2 or higher obesity (31%), followed by black men (21%), Hispanic women (18%), white women (17%), white men (12%), and Hispanic men (11.4%).

Dr. Sudan also pointed out that the black population has higher rates of hypertension and diabetes, compared with Hispanics and whites, while more white patients (56%) control their hypertension, compared with blacks (48%) and Hispanics (41%) (NCHS Data Brief 2012;107:1-8).

"Hypertension control is very important because hypertension is a risk factor for cardiovascular mortality," said Dr. Sudan. "If the medical control is not good, then we certainly want to consider bariatric surgery."

Dr. Sudan said the he’s planning on examining the database for geographic distribution and socioeconomic factors.

Dr. Sudan and Dr. Velanovich said they had no disclosures.

nmiller@frontlinemedcom.com

On Twitter @NaseemSMiller

ORLANDO – Although obesity is more prevalent among blacks, fewer get bariatric surgery, and for those who do, the outcomes are less efficacious than for whites and Hispanics, according to analysis of a national database, examining the influence of ethnicity on bariatric surgery.

"All qualified obese patients, particularly the rapidly growing black population, need improved access to bariatric surgery to reduce mortality," said Dr. Ranjan Sudan, vice chair of education in the department of surgery at Duke University, Durham, N.C. He presented his unpublished abstract at the annual Digestive Disease Week.

Studies have shown that bariatric surgery is an effective treatment for obesity and decreases mortality, but the reason behind the disparity and surgery outcomes is rather nuanced and not so clear (N. Engl. J. Med. 2007;357:753-61).

A 2012 study at the Louisiana State University System, Baton Rouge, found that white females appeared to lose more weight than did black females regardless of the type of bariatric surgery, although both races experienced surgical complications. Also, "black patients may be less likely to undergo bariatric surgery without insurance coverage," the authors wrote (Adv. Ther. 2012;29:970-8).

Meanwhile, a 2012 meta-analysis looking at ethnic differences in weight loss and diabetes remission after bariatric surgery found that for the percentage of excess weight loss, bariatric surgery was more effective in whites than in blacks, regardless of procedure type. "Further studies are needed to investigate the exact mechanisms behind these disparities and to determine whether ethnic differences exist in the remission of comorbidities after bariatric surgery," the authors wrote (Diabetes Care 2012;35:1951-8).

"It could be because of underlying difference in physiology among races," an area that is still poorly-understood, Dr. Vic Velanovich, professor of medicine at the University of South Florida, Tampa, said in an interview. Also, "Is this a problem of geographic variation?" he said, commenting on Dr. Sudan’s findings. "Are blacks getting their health care in such a way that they don’t have access to bariatric surgery? And the third issue is cultural. It could be very well that [the] cultural view of body image is different. So there are a lot of unanswered questions," said Dr. Velanovich, who was not involved in the study.

Dr. Sudan and his colleagues examined the primary Roux-en-Y gastric bypass surgery (RYGB) data from the American Society for Bariatric and Metabolic Surgery database, submitted by more than 1,000 surgeons and 700 hospitals between June 2007 and September 2011.

All patients gave research consent and were eligible for 1-year follow-up.

Of the 135,000 patients, 79% were white, 12% black, and 9% Hispanic. Compared with whites at baseline, black patients were younger (43 years vs. 46 years), heavier (body mass index of 50 kg/m² vs. 48 kg/m²), and were more often hypertensive (58% vs. 53%).

Among black patients who were undergoing RYGB, 15% were male, compared with 23% white and 22% Hispanic males. More black patients had a history of hypertension (57%), compared with whites (52%) and Hispanics (41%). Hispanic patients had the least comorbid disease burden, said Dr. Sudan.

Meanwhile, more white patients had diabetes (32%), compared with Hispanics (31%) and blacks (30%), at baseline.

Follow up rates were 60% in white patients, 50% in Hispanics, and 49% in blacks.

Overall, the benefits of RYGB were significant in the three groups at 1-year follow-up, but the procedure was less efficient for black patients, according to the analysis.

For instance, although fewer black patients had diabetes at baseline, at 1-year follow-up a higher percentage of them had diabetes with less decline in diabetes rates (from 30% to 13%, decline of 59%), compared with whites (from 32% to 11%; –65%), and Hispanics (from 31% to 12%; –61%.)

Black patients also had less decline in the mean body mass index (–30%), compared with whites (–34%), and Hispanics (–32%). Their hypertension also declined less (–35%) than in whites (–49%), and Hispanics (–50%).

The mortality rates within 30 days were similar for all three group (0.23%-0.26%), but black patients had a higher rate of total adverse events (22%), compared with whites and Hispanics (17% each).

The study has some limitations, said Dr. Sudan. Some of the data is self-reported, and researchers did not stratify disease severity by ethnicity.

Recent studies shows that grade 2 or higher obesity (BMI of 35 or more) is most prevalent among blacks (26%), compared with whites (15%) and Hispanics (15%). The overall rate for all ethnicities is 15.5%. (JAMA 2012;307:491-7). Black women also have the highest rate of grade 2 or higher obesity (31%), followed by black men (21%), Hispanic women (18%), white women (17%), white men (12%), and Hispanic men (11.4%).

Dr. Sudan also pointed out that the black population has higher rates of hypertension and diabetes, compared with Hispanics and whites, while more white patients (56%) control their hypertension, compared with blacks (48%) and Hispanics (41%) (NCHS Data Brief 2012;107:1-8).

"Hypertension control is very important because hypertension is a risk factor for cardiovascular mortality," said Dr. Sudan. "If the medical control is not good, then we certainly want to consider bariatric surgery."

Dr. Sudan said the he’s planning on examining the database for geographic distribution and socioeconomic factors.

Dr. Sudan and Dr. Velanovich said they had no disclosures.

nmiller@frontlinemedcom.com

On Twitter @NaseemSMiller

DENVER – Encasing implantable cardioverter-defibrillators and cardiac resynchronization therapy devices in a proprietary antibiotic-impregnated envelope during implantation was associated with a low 90-day major infection rate in an interim analysis of a large prospective multicenter study.

The CITADEL/CENTURION study involves 1,000 patients who underwent ICD or CRT device replacement using the antibacterial envelope at 55 U.S. centers. A major device infection – defined as an infection involving the device pocket, deep tissue, or endocarditis – occurred in one patient through 3 months of prospective follow-up, for an infection incidence of 0.1%, Dr. Charles Henrikson reported at the annual meeting of the Heart Rhythm Society.

CITADEL/CENTURION is not a randomized trial. Instead, the control group consists of 533 Canadian patients in a published study, all of whom underwent ICD or CRT replacement because of device advisories or recalls. The major device infection rate in this retrospective study (JAMA 2006;295:1907-11) during a mean 2.7 months following device replacement was 1.9%, or roughly 19-fold greater than in CITADEL/CENTURION, noted Dr. Henrikson of Oregon Health and Science University, Portland.

Device replacement is a known risk factor for major device infections, which carry a substantial toll in terms of morbidity, mortality, and expense.

The antibacterial envelope, known as AIGISRx, has received Food and Drug Administration approval and is commercially available. The antibacterial envelope is designed to prevent device migration as well as infections. "It changes the device from something that’s slick and slides right in into something with an incredibly high coefficient of friction, so you need to make a larger pocket to put it in. That’s why we’re paying a lot of attention to the hematoma rate," according to Dr. Henrikson.

The device consists of a nonresorbable polypropylene mesh coated with a resorbable polymer layer, which releases rifampin and minocycline for 7-10 days. These two antibiotics are active against the pathogens that cause most device infections, including both methicillin-sensitive and -resistant Staphylococcus aureus as well as S. epidermis.

The indication for device replacement in CITADEL/CENTURION was end of battery life in about three-quarters of patients, with device upgrades and lead revisions accounting for nearly all of the rest. Explantation because of device infection was a contraindication to study participation. All subjects were on perioperative prophylactic antibiotics, as were the historical controls.

The chief device-related complication recorded during the study was major pocket hematoma requiring a change in patient management, typically open drainage or transfusion. The complication occurred in 1.5% of patients, as compared to 2.25% of the historical controls.

Two of the 1,000 patients developed generalized rashes thought by independent reviewers to be possibly related to AIGISRx.

The plan is to monitor CITADEL/CENTURION participants for device infections and mechanical complications through 12 months, Dr. Henrikson explained. Only the 3-month data were available for presentation at a late-breaking clinical trials session during Heart Rhythm 2013.

CITADEL/CENTURION is sponsored by TYRX, which markets AIGISRx. Dr. Henrikson reported having received research support from the company.

bjancin@frontlinemedcom.com

DENVER – Encasing implantable cardioverter-defibrillators and cardiac resynchronization therapy devices in a proprietary antibiotic-impregnated envelope during implantation was associated with a low 90-day major infection rate in an interim analysis of a large prospective multicenter study.

The CITADEL/CENTURION study involves 1,000 patients who underwent ICD or CRT device replacement using the antibacterial envelope at 55 U.S. centers. A major device infection – defined as an infection involving the device pocket, deep tissue, or endocarditis – occurred in one patient through 3 months of prospective follow-up, for an infection incidence of 0.1%, Dr. Charles Henrikson reported at the annual meeting of the Heart Rhythm Society.

CITADEL/CENTURION is not a randomized trial. Instead, the control group consists of 533 Canadian patients in a published study, all of whom underwent ICD or CRT replacement because of device advisories or recalls. The major device infection rate in this retrospective study (JAMA 2006;295:1907-11) during a mean 2.7 months following device replacement was 1.9%, or roughly 19-fold greater than in CITADEL/CENTURION, noted Dr. Henrikson of Oregon Health and Science University, Portland.

Device replacement is a known risk factor for major device infections, which carry a substantial toll in terms of morbidity, mortality, and expense.

The antibacterial envelope, known as AIGISRx, has received Food and Drug Administration approval and is commercially available. The antibacterial envelope is designed to prevent device migration as well as infections. "It changes the device from something that’s slick and slides right in into something with an incredibly high coefficient of friction, so you need to make a larger pocket to put it in. That’s why we’re paying a lot of attention to the hematoma rate," according to Dr. Henrikson.

The device consists of a nonresorbable polypropylene mesh coated with a resorbable polymer layer, which releases rifampin and minocycline for 7-10 days. These two antibiotics are active against the pathogens that cause most device infections, including both methicillin-sensitive and -resistant Staphylococcus aureus as well as S. epidermis.

The indication for device replacement in CITADEL/CENTURION was end of battery life in about three-quarters of patients, with device upgrades and lead revisions accounting for nearly all of the rest. Explantation because of device infection was a contraindication to study participation. All subjects were on perioperative prophylactic antibiotics, as were the historical controls.

The chief device-related complication recorded during the study was major pocket hematoma requiring a change in patient management, typically open drainage or transfusion. The complication occurred in 1.5% of patients, as compared to 2.25% of the historical controls.

Two of the 1,000 patients developed generalized rashes thought by independent reviewers to be possibly related to AIGISRx.

The plan is to monitor CITADEL/CENTURION participants for device infections and mechanical complications through 12 months, Dr. Henrikson explained. Only the 3-month data were available for presentation at a late-breaking clinical trials session during Heart Rhythm 2013.

CITADEL/CENTURION is sponsored by TYRX, which markets AIGISRx. Dr. Henrikson reported having received research support from the company.

bjancin@frontlinemedcom.com

DENVER – Encasing implantable cardioverter-defibrillators and cardiac resynchronization therapy devices in a proprietary antibiotic-impregnated envelope during implantation was associated with a low 90-day major infection rate in an interim analysis of a large prospective multicenter study.

The CITADEL/CENTURION study involves 1,000 patients who underwent ICD or CRT device replacement using the antibacterial envelope at 55 U.S. centers. A major device infection – defined as an infection involving the device pocket, deep tissue, or endocarditis – occurred in one patient through 3 months of prospective follow-up, for an infection incidence of 0.1%, Dr. Charles Henrikson reported at the annual meeting of the Heart Rhythm Society.

CITADEL/CENTURION is not a randomized trial. Instead, the control group consists of 533 Canadian patients in a published study, all of whom underwent ICD or CRT replacement because of device advisories or recalls. The major device infection rate in this retrospective study (JAMA 2006;295:1907-11) during a mean 2.7 months following device replacement was 1.9%, or roughly 19-fold greater than in CITADEL/CENTURION, noted Dr. Henrikson of Oregon Health and Science University, Portland.

Device replacement is a known risk factor for major device infections, which carry a substantial toll in terms of morbidity, mortality, and expense.

The antibacterial envelope, known as AIGISRx, has received Food and Drug Administration approval and is commercially available. The antibacterial envelope is designed to prevent device migration as well as infections. "It changes the device from something that’s slick and slides right in into something with an incredibly high coefficient of friction, so you need to make a larger pocket to put it in. That’s why we’re paying a lot of attention to the hematoma rate," according to Dr. Henrikson.

The device consists of a nonresorbable polypropylene mesh coated with a resorbable polymer layer, which releases rifampin and minocycline for 7-10 days. These two antibiotics are active against the pathogens that cause most device infections, including both methicillin-sensitive and -resistant Staphylococcus aureus as well as S. epidermis.

The indication for device replacement in CITADEL/CENTURION was end of battery life in about three-quarters of patients, with device upgrades and lead revisions accounting for nearly all of the rest. Explantation because of device infection was a contraindication to study participation. All subjects were on perioperative prophylactic antibiotics, as were the historical controls.

The chief device-related complication recorded during the study was major pocket hematoma requiring a change in patient management, typically open drainage or transfusion. The complication occurred in 1.5% of patients, as compared to 2.25% of the historical controls.

Two of the 1,000 patients developed generalized rashes thought by independent reviewers to be possibly related to AIGISRx.

The plan is to monitor CITADEL/CENTURION participants for device infections and mechanical complications through 12 months, Dr. Henrikson explained. Only the 3-month data were available for presentation at a late-breaking clinical trials session during Heart Rhythm 2013.

CITADEL/CENTURION is sponsored by TYRX, which markets AIGISRx. Dr. Henrikson reported having received research support from the company.

bjancin@frontlinemedcom.com

A multidisciplinary postoperative care program of patient and staff education, early patient mobilization, and pulmonary interventions has begun to reduce the excessive rate of postsurgical pulmonary complications at a large urban safety-net hospital, according to a report published online June 5 in JAMA Surgery (formerly Archives of Surgery).

"We are eager to monitor our outcomes over a longer period, and we are stimulated by the possibility that postoperative complications may be diminished by adherence to simple, inexpensive, easily performed patient care strategies," said Dr. Michael R. Cassidy of the department of surgery, Boston University Medical Center, and his associates.

When data collected in the National Surgical Quality Improvement Program (NSQIP) revealed that their center "was a high outlier for all measured postoperative pulmonary complications," the investigators formed a multidisciplinary group to address the problem.

BUMC is the largest safety-net facility in New England. The annual income of more than half of its patients is below $20,420, approximately 25% of its patients do not speak English, and 70% belong to racial or ethnic minorities, the investigators noted.

The committee included representatives from the hospital’s departments of surgery, nursing, and quality improvement, as well as from the units on respiratory therapy, preoperative assessment, infection control, and physical therapy. To devise a program to reduce the incidence of adverse pulmonary complications, these members reviewed the sparse literature regarding prevention of postoperative pneumonia and audited postsurgical pulmonary practices at their medical center.

The audit found that patients received no formal preoperative education about the importance of lung expansion, mobility, and other strategies to prevent pulmonary complications, and that families usually weren’t included in whatever minimal education did take place. In addition, physicians’ orders for nurses regarding postoperative pulmonary care "were irregular or absent."

The program that was then developed was given the acronym "I COUGH" to help physicians, nurses, patients, and families remember its key principles: Incentive spirometry, Coughing and deep breathing, Oral care, Understanding, Getting out of bed frequently, and Head-of-the-bed elevation. It was intended for all patients on the general surgery and vascular surgery services.

I COUGH included brochures, a video, and posters to educate patients, families, nurses, and physicians about the importance of pulmonary care. Proper use of incentive spirometry was demonstrated, the use of mouthwash and toothbrushing was recommended at least twice a day, and elevation of the head of the bed to at least 30 degrees was advocated. All this information was reinforced at preoperative clinic visits and in the preoperative holding area just before surgery. Nursing staff also reiterated the information after the procedures, as did surgeons, attending physicians, and house staff during rounds.

The effort also included standardized electronic physician order sets with "specific and detailed orders for all elements of the I COUGH program." These included instructions for patients to perform deep breathing and coughing every 2 hours; for patients to perform incentive spirometry 10 times every hour while awake; for nurses to document incentive spirometry volume every 4 hours and to ensure that the head of the patient’s bed was elevated to at least 30 degrees; for patients to walk at least once on the day of operation unless contraindicated; and for patients to get out of bed and sit in a chair for a while at least 3 times per day.

Dr. Cassidy and his associates then compared data collected during the year before I COUGH was implemented to that collected during the year afterward.

Before I COUGH, 80% of 250 patients were in bed at the time of the audit, with only 19.6% seated in a chair or walking. After I COUGH, 69.1% of 250 patients were out of bed. Before I COUGH, only 52.8% of patients had an incentive spirometer within reach and an unknown number were using it appropriately, whereas afterward 77.2% of patients had the device within reach and were using it appropriately. Both findings were statistically significant.

The incidence of postoperative pneumonia was 2.6% before I COUGH, which dropped to 1.6% in the year afterward (P = .09). Similarly, the incidence of unplanned intubations was 2.0% before I COUGH, which decreased to 1.2% afterward, the authors reported (JAMA Surg. 2013 June 5 [doi: 10.1001/jamasurg.2013.358]).

These successes are due in part to the involvement of the multidisciplinary team at all stages of development of the I COUGH program, the investigators said.

"We have not imposed a standard of care by mandate, but instead have involved nursing leadership and practicing ward and ICU nurses in the process of redefining the culture.

"We found that involvement of representatives of each discipline significantly increased acceptance of the I COUGH program, and instilled a sense of commitment and pride that could not have been achieved by simply instituting and enforcing a policy without input from all parties involved," Dr. Cassidy and his colleagues added.

While the study had several limitations, including variations in data-gathering techniques and NSQIP reporting protocols, the investigators pointed to "substantial differences in nursing practice documented between the audits before and after I COUGH implementation."

"We believe that a favorable change in practice occurred as a result of our program," they wrote.

The investigators reported having no financial conflicts of interest.

A multidisciplinary postoperative care program of patient and staff education, early patient mobilization, and pulmonary interventions has begun to reduce the excessive rate of postsurgical pulmonary complications at a large urban safety-net hospital, according to a report published online June 5 in JAMA Surgery (formerly Archives of Surgery).

"We are eager to monitor our outcomes over a longer period, and we are stimulated by the possibility that postoperative complications may be diminished by adherence to simple, inexpensive, easily performed patient care strategies," said Dr. Michael R. Cassidy of the department of surgery, Boston University Medical Center, and his associates.

When data collected in the National Surgical Quality Improvement Program (NSQIP) revealed that their center "was a high outlier for all measured postoperative pulmonary complications," the investigators formed a multidisciplinary group to address the problem.

BUMC is the largest safety-net facility in New England. The annual income of more than half of its patients is below $20,420, approximately 25% of its patients do not speak English, and 70% belong to racial or ethnic minorities, the investigators noted.

The committee included representatives from the hospital’s departments of surgery, nursing, and quality improvement, as well as from the units on respiratory therapy, preoperative assessment, infection control, and physical therapy. To devise a program to reduce the incidence of adverse pulmonary complications, these members reviewed the sparse literature regarding prevention of postoperative pneumonia and audited postsurgical pulmonary practices at their medical center.

The audit found that patients received no formal preoperative education about the importance of lung expansion, mobility, and other strategies to prevent pulmonary complications, and that families usually weren’t included in whatever minimal education did take place. In addition, physicians’ orders for nurses regarding postoperative pulmonary care "were irregular or absent."

The program that was then developed was given the acronym "I COUGH" to help physicians, nurses, patients, and families remember its key principles: Incentive spirometry, Coughing and deep breathing, Oral care, Understanding, Getting out of bed frequently, and Head-of-the-bed elevation. It was intended for all patients on the general surgery and vascular surgery services.

I COUGH included brochures, a video, and posters to educate patients, families, nurses, and physicians about the importance of pulmonary care. Proper use of incentive spirometry was demonstrated, the use of mouthwash and toothbrushing was recommended at least twice a day, and elevation of the head of the bed to at least 30 degrees was advocated. All this information was reinforced at preoperative clinic visits and in the preoperative holding area just before surgery. Nursing staff also reiterated the information after the procedures, as did surgeons, attending physicians, and house staff during rounds.

The effort also included standardized electronic physician order sets with "specific and detailed orders for all elements of the I COUGH program." These included instructions for patients to perform deep breathing and coughing every 2 hours; for patients to perform incentive spirometry 10 times every hour while awake; for nurses to document incentive spirometry volume every 4 hours and to ensure that the head of the patient’s bed was elevated to at least 30 degrees; for patients to walk at least once on the day of operation unless contraindicated; and for patients to get out of bed and sit in a chair for a while at least 3 times per day.

Dr. Cassidy and his associates then compared data collected during the year before I COUGH was implemented to that collected during the year afterward.

Before I COUGH, 80% of 250 patients were in bed at the time of the audit, with only 19.6% seated in a chair or walking. After I COUGH, 69.1% of 250 patients were out of bed. Before I COUGH, only 52.8% of patients had an incentive spirometer within reach and an unknown number were using it appropriately, whereas afterward 77.2% of patients had the device within reach and were using it appropriately. Both findings were statistically significant.

The incidence of postoperative pneumonia was 2.6% before I COUGH, which dropped to 1.6% in the year afterward (P = .09). Similarly, the incidence of unplanned intubations was 2.0% before I COUGH, which decreased to 1.2% afterward, the authors reported (JAMA Surg. 2013 June 5 [doi: 10.1001/jamasurg.2013.358]).

These successes are due in part to the involvement of the multidisciplinary team at all stages of development of the I COUGH program, the investigators said.

"We have not imposed a standard of care by mandate, but instead have involved nursing leadership and practicing ward and ICU nurses in the process of redefining the culture.

"We found that involvement of representatives of each discipline significantly increased acceptance of the I COUGH program, and instilled a sense of commitment and pride that could not have been achieved by simply instituting and enforcing a policy without input from all parties involved," Dr. Cassidy and his colleagues added.

While the study had several limitations, including variations in data-gathering techniques and NSQIP reporting protocols, the investigators pointed to "substantial differences in nursing practice documented between the audits before and after I COUGH implementation."

"We believe that a favorable change in practice occurred as a result of our program," they wrote.

The investigators reported having no financial conflicts of interest.

A multidisciplinary postoperative care program of patient and staff education, early patient mobilization, and pulmonary interventions has begun to reduce the excessive rate of postsurgical pulmonary complications at a large urban safety-net hospital, according to a report published online June 5 in JAMA Surgery (formerly Archives of Surgery).

"We are eager to monitor our outcomes over a longer period, and we are stimulated by the possibility that postoperative complications may be diminished by adherence to simple, inexpensive, easily performed patient care strategies," said Dr. Michael R. Cassidy of the department of surgery, Boston University Medical Center, and his associates.

When data collected in the National Surgical Quality Improvement Program (NSQIP) revealed that their center "was a high outlier for all measured postoperative pulmonary complications," the investigators formed a multidisciplinary group to address the problem.

BUMC is the largest safety-net facility in New England. The annual income of more than half of its patients is below $20,420, approximately 25% of its patients do not speak English, and 70% belong to racial or ethnic minorities, the investigators noted.

The committee included representatives from the hospital’s departments of surgery, nursing, and quality improvement, as well as from the units on respiratory therapy, preoperative assessment, infection control, and physical therapy. To devise a program to reduce the incidence of adverse pulmonary complications, these members reviewed the sparse literature regarding prevention of postoperative pneumonia and audited postsurgical pulmonary practices at their medical center.

The audit found that patients received no formal preoperative education about the importance of lung expansion, mobility, and other strategies to prevent pulmonary complications, and that families usually weren’t included in whatever minimal education did take place. In addition, physicians’ orders for nurses regarding postoperative pulmonary care "were irregular or absent."

The program that was then developed was given the acronym "I COUGH" to help physicians, nurses, patients, and families remember its key principles: Incentive spirometry, Coughing and deep breathing, Oral care, Understanding, Getting out of bed frequently, and Head-of-the-bed elevation. It was intended for all patients on the general surgery and vascular surgery services.

I COUGH included brochures, a video, and posters to educate patients, families, nurses, and physicians about the importance of pulmonary care. Proper use of incentive spirometry was demonstrated, the use of mouthwash and toothbrushing was recommended at least twice a day, and elevation of the head of the bed to at least 30 degrees was advocated. All this information was reinforced at preoperative clinic visits and in the preoperative holding area just before surgery. Nursing staff also reiterated the information after the procedures, as did surgeons, attending physicians, and house staff during rounds.

The effort also included standardized electronic physician order sets with "specific and detailed orders for all elements of the I COUGH program." These included instructions for patients to perform deep breathing and coughing every 2 hours; for patients to perform incentive spirometry 10 times every hour while awake; for nurses to document incentive spirometry volume every 4 hours and to ensure that the head of the patient’s bed was elevated to at least 30 degrees; for patients to walk at least once on the day of operation unless contraindicated; and for patients to get out of bed and sit in a chair for a while at least 3 times per day.

Dr. Cassidy and his associates then compared data collected during the year before I COUGH was implemented to that collected during the year afterward.

Before I COUGH, 80% of 250 patients were in bed at the time of the audit, with only 19.6% seated in a chair or walking. After I COUGH, 69.1% of 250 patients were out of bed. Before I COUGH, only 52.8% of patients had an incentive spirometer within reach and an unknown number were using it appropriately, whereas afterward 77.2% of patients had the device within reach and were using it appropriately. Both findings were statistically significant.

The incidence of postoperative pneumonia was 2.6% before I COUGH, which dropped to 1.6% in the year afterward (P = .09). Similarly, the incidence of unplanned intubations was 2.0% before I COUGH, which decreased to 1.2% afterward, the authors reported (JAMA Surg. 2013 June 5 [doi: 10.1001/jamasurg.2013.358]).

These successes are due in part to the involvement of the multidisciplinary team at all stages of development of the I COUGH program, the investigators said.

"We have not imposed a standard of care by mandate, but instead have involved nursing leadership and practicing ward and ICU nurses in the process of redefining the culture.

"We found that involvement of representatives of each discipline significantly increased acceptance of the I COUGH program, and instilled a sense of commitment and pride that could not have been achieved by simply instituting and enforcing a policy without input from all parties involved," Dr. Cassidy and his colleagues added.

While the study had several limitations, including variations in data-gathering techniques and NSQIP reporting protocols, the investigators pointed to "substantial differences in nursing practice documented between the audits before and after I COUGH implementation."

"We believe that a favorable change in practice occurred as a result of our program," they wrote.

The investigators reported having no financial conflicts of interest.

In patients with mild to moderate obesity and poorly controlled type 2 diabetes, adding Roux-en-Y gastric bypass surgery to intensive lifestyle and medical management more than doubles the likelihood of achieving weight-loss and metabolic goals within 1 year, according to the results of a randomized trial reported in the June 5 issue of JAMA.

However, this potential benefit must be weighed against what appears to be a moderate risk of serious adverse events, even when the procedure is done by experienced medical teams, said Dr. Sayeed Ikramuddin of the department of surgery, University of Minnesota, Minneapolis, and his associates.

In addition, the permanence of weight loss and metabolic results following the first 1-2 years after the procedure remains uncertain, as do long-term adverse events, because so few studies have adequately followed patients past that point, the investigators wrote.

Dr. Ikramuddin and his colleagues drew these conclusions from their randomized trial of 120 patients with mild to moderate obesity (body mass index, 30.0-39.9 kg/m²) whose type 2 diabetes was poorly controlled on standard medical therapy.

In a separate report in the same issue of JAMA, Dr. Melinda Maggard-Gibbons of the University of California, Los Angeles, and her associates reported their findings from a systematic review of the literature regarding all types of bariatric surgery in similar patients with mild obesity (BMI, 30-35). They found that there still is not sufficient evidence to determine whether bariatric surgery is warranted in this patient population because of the lack of long-term data on safety and efficacy. They identified only four studies with a follow-up of more than 2 years, and those had small sample sizes or poor methodology that "preclude definitive conclusions."

Thus, neither of these investigations can support or refute the suggestion by some proponents that bariatric surgery should be extended to diabetic patients with low-grade obesity to improve their glycemic control.

In their prospective, unblinded clinical trial, Dr. Ikramuddin and his associates offered a free, intensive lifestyle and medical-therapy weight control program to the 120 study subjects at one academic medical center in Minnesota, one in New York, and two in Taiwan over a 3-year period. All patients were between 30 and 67 years of age and had hemoglobin A_1c (HbA_1c) levels of 8% or higher (mean, 9.6%); the average duration of diabetes was 9 years.

The program included daily weigh-ins and detailed diaries of eating and exercise, with caloric intake goals of 1,200-1,800 kcal/day and moderate physical activity for at least 325 min/week to achieve a weight loss of 1-2 pounds/week. The study subjects met regularly with trained interventionists to discuss weight management and to enhance adherence.

Patients could add orlistat or, until it was withdrawn from the market, sibutramine for weight control. Medications for glycemic control were added as necessary, as were aspirin therapy and medications to control cholesterol levels and blood pressure.

Half of the study subjects were then randomly assigned to undergo laparoscopic Roux-en-Y gastric bypass. This group was given multivitamin and mineral supplements.

The endpoint of the study was a triple outcome endorsed by the American Diabetes Association: an HbA_1c level of less than 7%, a low-density lipoprotein (LDL) cholesterol level of less than 100 mg/dL, and a systolic blood pressure of less than 130 mm Hg at 1-year follow-up.

A total of 28 patients (49%) in the gastric bypass group achieved this end point, compared with only 11 (19%) in the lifestyle/medical management group, Dr. Ikramuddin and his colleagues reported (JAMA 2013;309:2240-49).

Of these three components of the combined endpoint, only HbA_1c level showed a significant difference between the two study groups: 43 (75%) of the surgery group achieved an HbA_1c level under 7%, compared with just 18 (32%) of the lifestyle/medical management group.

The difference in outcomes between the two groups was attributed chiefly to their difference in weight loss. The mean loss at 1 year was 26% of baseline weight after gastric bypass, compared with 8% with the intensive lifestyle/medication program.

Patients in the surgery group continued to lose weight throughout the year of follow-up, while those in the other group tended to lose weight during the first 6 months and plateau after that.

On average, at 1 year the patients in the surgery group required three fewer medications than did those in the other group to manage glycemia, dyslipidemia, and hypertension.

However, patients who underwent gastric bypass had 50% more serious adverse events and 55% more nonserious adverse events than did those who did not. "All surgeons performing gastric bypass in this study were experts; thus the occurrence of serious complications must be factored into the design of larger trials of effectiveness for patients with moderate obesity," Dr. Ikramuddin and his associates said.

The 22 serious adverse events in the surgery group included 4 perioperative and 6 late postoperative complications. The most serious complications involved anastomotic leakage that was not detected on routine postoperative upper-GI contrast studies. One of these patients eventually required extracorporeal membrane oxygenation; she developed anoxic brain injury, required lower-extremity amputation, and remains permanently disabled.

Nutritional deficiencies also developed relatively often in the bypass group, despite supplementation. These included iron, vitamin B, and vitamin D deficiencies, as well as hypoalbuminemia.

Other adverse events known to develop more than 1 year after gastric bypass include weight regain, internal hernias, anastomotic ulcers, hypoglycemia, anastomotic strictures, bleeding, bowel obstruction, kidney stones, and fractures.

Overall, these findings show that "the merit of gastric bypass treatment of moderately obese patients with type 2 diabetes depends on whether potential benefits make [these] risks acceptable," the investigators said.

In their systematic review of the literature, Dr. Maggard-Gibbons and her associates reviewed 1,291 studies but could find only 3 randomized trials that came close to directly comparing surgical against nonsurgical interventions in patients with BMIs of 30-35. The total number of patients in these trials was only 290, and individual-level data were available only for 13 patients with type 2 diabetes in this weight category.

They then altered their search criteria to include studies of patients with BMIs of 35-40 and studies that did not directly compare outcomes between surgical and nonsurgical approaches. Even then, "many of the studies were from single surgeons at single academic institutions and may not be representative of results in a general population of patients and surgeons."

Of greatest concern was the fact that "we found no long-term studies of postsurgery adverse events in patients with diabetes within our target BMI range," they said (JAMA 2013;309:2250-61).

The limited studies that were available consistently found that short-term weight loss and glycemic control were better for patients treated with bariatric surgery than for those who were not. However, the durability of these results is uncertain, and the amount of weight loss did not always correlate with the degree of improvement of metabolic factors. And it is not yet known whether these outcomes translate into reduction in the important macrovascular and microvascular effects of diabetes.

Moreover, although surgical complications were not common, those that did occur often were serious and required significant intervention. And of the few studies that did track later complications, most were not designed to do so and covered only "surgeon-reported outcomes from selected, experienced centers."

Thus, "the evidence is insufficient to reach conclusions about the appropriate use of bariatric surgery in this patient population, [and] performance of these procedures in this target population should be under close scientific scrutiny," Dr. Maggard-Gibbons and her colleagues said.

Dr. Irkamuddin’s study was supported by Covidien and the National Center for Advancing Translational Sciences. Dr. Irkamuddin reported ties to Novo Nordisk, USGI, and other companies; his associates reported ties to numerous industry sources. Dr. Maggard-Gibbons’ study was supported by the Agency for Healthcare Research and Quality; she and her associates reported no relevant financial conflicts of interest.

In patients with mild to moderate obesity and poorly controlled type 2 diabetes, adding Roux-en-Y gastric bypass surgery to intensive lifestyle and medical management more than doubles the likelihood of achieving weight-loss and metabolic goals within 1 year, according to the results of a randomized trial reported in the June 5 issue of JAMA.

However, this potential benefit must be weighed against what appears to be a moderate risk of serious adverse events, even when the procedure is done by experienced medical teams, said Dr. Sayeed Ikramuddin of the department of surgery, University of Minnesota, Minneapolis, and his associates.

In addition, the permanence of weight loss and metabolic results following the first 1-2 years after the procedure remains uncertain, as do long-term adverse events, because so few studies have adequately followed patients past that point, the investigators wrote.

Dr. Ikramuddin and his colleagues drew these conclusions from their randomized trial of 120 patients with mild to moderate obesity (body mass index, 30.0-39.9 kg/m²) whose type 2 diabetes was poorly controlled on standard medical therapy.

In a separate report in the same issue of JAMA, Dr. Melinda Maggard-Gibbons of the University of California, Los Angeles, and her associates reported their findings from a systematic review of the literature regarding all types of bariatric surgery in similar patients with mild obesity (BMI, 30-35). They found that there still is not sufficient evidence to determine whether bariatric surgery is warranted in this patient population because of the lack of long-term data on safety and efficacy. They identified only four studies with a follow-up of more than 2 years, and those had small sample sizes or poor methodology that "preclude definitive conclusions."

Thus, neither of these investigations can support or refute the suggestion by some proponents that bariatric surgery should be extended to diabetic patients with low-grade obesity to improve their glycemic control.

In their prospective, unblinded clinical trial, Dr. Ikramuddin and his associates offered a free, intensive lifestyle and medical-therapy weight control program to the 120 study subjects at one academic medical center in Minnesota, one in New York, and two in Taiwan over a 3-year period. All patients were between 30 and 67 years of age and had hemoglobin A_1c (HbA_1c) levels of 8% or higher (mean, 9.6%); the average duration of diabetes was 9 years.

The program included daily weigh-ins and detailed diaries of eating and exercise, with caloric intake goals of 1,200-1,800 kcal/day and moderate physical activity for at least 325 min/week to achieve a weight loss of 1-2 pounds/week. The study subjects met regularly with trained interventionists to discuss weight management and to enhance adherence.

Patients could add orlistat or, until it was withdrawn from the market, sibutramine for weight control. Medications for glycemic control were added as necessary, as were aspirin therapy and medications to control cholesterol levels and blood pressure.

Half of the study subjects were then randomly assigned to undergo laparoscopic Roux-en-Y gastric bypass. This group was given multivitamin and mineral supplements.

The endpoint of the study was a triple outcome endorsed by the American Diabetes Association: an HbA_1c level of less than 7%, a low-density lipoprotein (LDL) cholesterol level of less than 100 mg/dL, and a systolic blood pressure of less than 130 mm Hg at 1-year follow-up.

A total of 28 patients (49%) in the gastric bypass group achieved this end point, compared with only 11 (19%) in the lifestyle/medical management group, Dr. Ikramuddin and his colleagues reported (JAMA 2013;309:2240-49).

Of these three components of the combined endpoint, only HbA_1c level showed a significant difference between the two study groups: 43 (75%) of the surgery group achieved an HbA_1c level under 7%, compared with just 18 (32%) of the lifestyle/medical management group.

The difference in outcomes between the two groups was attributed chiefly to their difference in weight loss. The mean loss at 1 year was 26% of baseline weight after gastric bypass, compared with 8% with the intensive lifestyle/medication program.

Patients in the surgery group continued to lose weight throughout the year of follow-up, while those in the other group tended to lose weight during the first 6 months and plateau after that.

On average, at 1 year the patients in the surgery group required three fewer medications than did those in the other group to manage glycemia, dyslipidemia, and hypertension.

However, patients who underwent gastric bypass had 50% more serious adverse events and 55% more nonserious adverse events than did those who did not. "All surgeons performing gastric bypass in this study were experts; thus the occurrence of serious complications must be factored into the design of larger trials of effectiveness for patients with moderate obesity," Dr. Ikramuddin and his associates said.

The 22 serious adverse events in the surgery group included 4 perioperative and 6 late postoperative complications. The most serious complications involved anastomotic leakage that was not detected on routine postoperative upper-GI contrast studies. One of these patients eventually required extracorporeal membrane oxygenation; she developed anoxic brain injury, required lower-extremity amputation, and remains permanently disabled.

Nutritional deficiencies also developed relatively often in the bypass group, despite supplementation. These included iron, vitamin B, and vitamin D deficiencies, as well as hypoalbuminemia.

Other adverse events known to develop more than 1 year after gastric bypass include weight regain, internal hernias, anastomotic ulcers, hypoglycemia, anastomotic strictures, bleeding, bowel obstruction, kidney stones, and fractures.

Overall, these findings show that "the merit of gastric bypass treatment of moderately obese patients with type 2 diabetes depends on whether potential benefits make [these] risks acceptable," the investigators said.

In their systematic review of the literature, Dr. Maggard-Gibbons and her associates reviewed 1,291 studies but could find only 3 randomized trials that came close to directly comparing surgical against nonsurgical interventions in patients with BMIs of 30-35. The total number of patients in these trials was only 290, and individual-level data were available only for 13 patients with type 2 diabetes in this weight category.

They then altered their search criteria to include studies of patients with BMIs of 35-40 and studies that did not directly compare outcomes between surgical and nonsurgical approaches. Even then, "many of the studies were from single surgeons at single academic institutions and may not be representative of results in a general population of patients and surgeons."

Of greatest concern was the fact that "we found no long-term studies of postsurgery adverse events in patients with diabetes within our target BMI range," they said (JAMA 2013;309:2250-61).

The limited studies that were available consistently found that short-term weight loss and glycemic control were better for patients treated with bariatric surgery than for those who were not. However, the durability of these results is uncertain, and the amount of weight loss did not always correlate with the degree of improvement of metabolic factors. And it is not yet known whether these outcomes translate into reduction in the important macrovascular and microvascular effects of diabetes.

Moreover, although surgical complications were not common, those that did occur often were serious and required significant intervention. And of the few studies that did track later complications, most were not designed to do so and covered only "surgeon-reported outcomes from selected, experienced centers."

Thus, "the evidence is insufficient to reach conclusions about the appropriate use of bariatric surgery in this patient population, [and] performance of these procedures in this target population should be under close scientific scrutiny," Dr. Maggard-Gibbons and her colleagues said.

Dr. Irkamuddin’s study was supported by Covidien and the National Center for Advancing Translational Sciences. Dr. Irkamuddin reported ties to Novo Nordisk, USGI, and other companies; his associates reported ties to numerous industry sources. Dr. Maggard-Gibbons’ study was supported by the Agency for Healthcare Research and Quality; she and her associates reported no relevant financial conflicts of interest.

In patients with mild to moderate obesity and poorly controlled type 2 diabetes, adding Roux-en-Y gastric bypass surgery to intensive lifestyle and medical management more than doubles the likelihood of achieving weight-loss and metabolic goals within 1 year, according to the results of a randomized trial reported in the June 5 issue of JAMA.

However, this potential benefit must be weighed against what appears to be a moderate risk of serious adverse events, even when the procedure is done by experienced medical teams, said Dr. Sayeed Ikramuddin of the department of surgery, University of Minnesota, Minneapolis, and his associates.

In addition, the permanence of weight loss and metabolic results following the first 1-2 years after the procedure remains uncertain, as do long-term adverse events, because so few studies have adequately followed patients past that point, the investigators wrote.

Dr. Ikramuddin and his colleagues drew these conclusions from their randomized trial of 120 patients with mild to moderate obesity (body mass index, 30.0-39.9 kg/m²) whose type 2 diabetes was poorly controlled on standard medical therapy.

In a separate report in the same issue of JAMA, Dr. Melinda Maggard-Gibbons of the University of California, Los Angeles, and her associates reported their findings from a systematic review of the literature regarding all types of bariatric surgery in similar patients with mild obesity (BMI, 30-35). They found that there still is not sufficient evidence to determine whether bariatric surgery is warranted in this patient population because of the lack of long-term data on safety and efficacy. They identified only four studies with a follow-up of more than 2 years, and those had small sample sizes or poor methodology that "preclude definitive conclusions."

Thus, neither of these investigations can support or refute the suggestion by some proponents that bariatric surgery should be extended to diabetic patients with low-grade obesity to improve their glycemic control.

In their prospective, unblinded clinical trial, Dr. Ikramuddin and his associates offered a free, intensive lifestyle and medical-therapy weight control program to the 120 study subjects at one academic medical center in Minnesota, one in New York, and two in Taiwan over a 3-year period. All patients were between 30 and 67 years of age and had hemoglobin A_1c (HbA_1c) levels of 8% or higher (mean, 9.6%); the average duration of diabetes was 9 years.

The program included daily weigh-ins and detailed diaries of eating and exercise, with caloric intake goals of 1,200-1,800 kcal/day and moderate physical activity for at least 325 min/week to achieve a weight loss of 1-2 pounds/week. The study subjects met regularly with trained interventionists to discuss weight management and to enhance adherence.

Patients could add orlistat or, until it was withdrawn from the market, sibutramine for weight control. Medications for glycemic control were added as necessary, as were aspirin therapy and medications to control cholesterol levels and blood pressure.

Half of the study subjects were then randomly assigned to undergo laparoscopic Roux-en-Y gastric bypass. This group was given multivitamin and mineral supplements.

The endpoint of the study was a triple outcome endorsed by the American Diabetes Association: an HbA_1c level of less than 7%, a low-density lipoprotein (LDL) cholesterol level of less than 100 mg/dL, and a systolic blood pressure of less than 130 mm Hg at 1-year follow-up.

A total of 28 patients (49%) in the gastric bypass group achieved this end point, compared with only 11 (19%) in the lifestyle/medical management group, Dr. Ikramuddin and his colleagues reported (JAMA 2013;309:2240-49).

Of these three components of the combined endpoint, only HbA_1c level showed a significant difference between the two study groups: 43 (75%) of the surgery group achieved an HbA_1c level under 7%, compared with just 18 (32%) of the lifestyle/medical management group.

The difference in outcomes between the two groups was attributed chiefly to their difference in weight loss. The mean loss at 1 year was 26% of baseline weight after gastric bypass, compared with 8% with the intensive lifestyle/medication program.

Patients in the surgery group continued to lose weight throughout the year of follow-up, while those in the other group tended to lose weight during the first 6 months and plateau after that.

On average, at 1 year the patients in the surgery group required three fewer medications than did those in the other group to manage glycemia, dyslipidemia, and hypertension.

However, patients who underwent gastric bypass had 50% more serious adverse events and 55% more nonserious adverse events than did those who did not. "All surgeons performing gastric bypass in this study were experts; thus the occurrence of serious complications must be factored into the design of larger trials of effectiveness for patients with moderate obesity," Dr. Ikramuddin and his associates said.

The 22 serious adverse events in the surgery group included 4 perioperative and 6 late postoperative complications. The most serious complications involved anastomotic leakage that was not detected on routine postoperative upper-GI contrast studies. One of these patients eventually required extracorporeal membrane oxygenation; she developed anoxic brain injury, required lower-extremity amputation, and remains permanently disabled.

Nutritional deficiencies also developed relatively often in the bypass group, despite supplementation. These included iron, vitamin B, and vitamin D deficiencies, as well as hypoalbuminemia.

Other adverse events known to develop more than 1 year after gastric bypass include weight regain, internal hernias, anastomotic ulcers, hypoglycemia, anastomotic strictures, bleeding, bowel obstruction, kidney stones, and fractures.

Overall, these findings show that "the merit of gastric bypass treatment of moderately obese patients with type 2 diabetes depends on whether potential benefits make [these] risks acceptable," the investigators said.

In their systematic review of the literature, Dr. Maggard-Gibbons and her associates reviewed 1,291 studies but could find only 3 randomized trials that came close to directly comparing surgical against nonsurgical interventions in patients with BMIs of 30-35. The total number of patients in these trials was only 290, and individual-level data were available only for 13 patients with type 2 diabetes in this weight category.

They then altered their search criteria to include studies of patients with BMIs of 35-40 and studies that did not directly compare outcomes between surgical and nonsurgical approaches. Even then, "many of the studies were from single surgeons at single academic institutions and may not be representative of results in a general population of patients and surgeons."

Of greatest concern was the fact that "we found no long-term studies of postsurgery adverse events in patients with diabetes within our target BMI range," they said (JAMA 2013;309:2250-61).

The limited studies that were available consistently found that short-term weight loss and glycemic control were better for patients treated with bariatric surgery than for those who were not. However, the durability of these results is uncertain, and the amount of weight loss did not always correlate with the degree of improvement of metabolic factors. And it is not yet known whether these outcomes translate into reduction in the important macrovascular and microvascular effects of diabetes.

Moreover, although surgical complications were not common, those that did occur often were serious and required significant intervention. And of the few studies that did track later complications, most were not designed to do so and covered only "surgeon-reported outcomes from selected, experienced centers."

Thus, "the evidence is insufficient to reach conclusions about the appropriate use of bariatric surgery in this patient population, [and] performance of these procedures in this target population should be under close scientific scrutiny," Dr. Maggard-Gibbons and her colleagues said.

Dr. Irkamuddin’s study was supported by Covidien and the National Center for Advancing Translational Sciences. Dr. Irkamuddin reported ties to Novo Nordisk, USGI, and other companies; his associates reported ties to numerous industry sources. Dr. Maggard-Gibbons’ study was supported by the Agency for Healthcare Research and Quality; she and her associates reported no relevant financial conflicts of interest.

CHICAGO – The long wait for a new medical therapy for advanced radioactive-refractory thyroid cancer is drawing to a close.

Twice-daily oral sorafenib (Nexavar) nearly doubled the median time to disease progression from 5.8 months with placebo to 10.8 months (hazard ratio, 0.587; P less than .0001) among 417 patients in the double-blind, international phase III DECISION study.

The benefit of sorafenib on this primary endpoint was seen across all patient characteristics, including age, histology, and geographic region, principal investigator Dr. Marcia S. Brose said during the plenary session at the annual meeting of the American Society of Clinical Oncology.

Patrice Wendling/IMNG Medical Media

Median overall survival has not been reached for either arm, and will be strongly affected by the 71% of controls who crossed over to open-label treatment with the multikinase inhibitor.

No standard therapy exists for the 5%-15% of patients with thyroid cancer who are refractory to standard treatment with surgery and radioactive iodine (RAI). Doxorubicin (Adriamycin) chemotherapy was approved some 30 years ago, but it is ineffective and toxic.

"Sorafenib is a potential new treatment option for patients with locally advanced or metastatic radioactive-refractory differentiated thyroid cancer," said Dr. Brose, director of thyroid cancer therapeutics and head and neck clinical trials at the University of Pennsylvania, Philadelphia.

Approval sought in U.S. and abroad

DECISION (Study of sorafenib in locally advanced or metastatic patients with radioactive iodine refractory thyroid cancer) is the first phase III study to demonstrate treatment efficacy in this setting. Based on its results, a supplemental New Drug Application will be submitted for sorafenib by midyear in the United States, with global submissions to follow, according to study sponsors Bayer Healthcare Pharmaceuticals and Onyx Pharmaceuticals. The drug is already approved in the United States for advanced renal and liver cancer.

DECISION involved 417 patients in the United States, Europe, or Asia who had locally advanced or metastatic RAI-refractory differentiated thyroid cancer that had progressed within the previous 14 months and had received no prior chemotherapy, targeted therapy, or thalidomide. Patients received twice-daily sorafenib 400 mg or placebo. The majority had distant metastases (96%), 66% had papillary histology, and 61% had an ECOG performance status of 0. Their median age was 63 years.

Sorafenib did not induce any complete responses. Partial responses, defined by at least a 30% reduction in tumor size, occurred in 12.2% of sorafenib patients vs. 0.5% of controls, and lasted for a median of 10.2 months, Dr. Brose said. An additional 42% of patients experienced stable disease for more than 6 months, resulting in a disease control rate of 54% in the sorafenib arm vs. 34% in the placebo arm.

In all, 73% of sorafenib-treated patients had some tumor shrinkage, compared with 27% of placebo-treated patients, and this was often sufficient to relieve symptoms, she said.

It would have been nice to see more partial responses, but all responses were clinically meaningful, Dr. Brose said in an interview.

"Unlike other cancers, what’s interesting is that these patients can have 100 nodules in their chest and actually experience very few symptoms, but what will kill them is when those grow," she said. "So the more clinically important number that is going to prevent the hospitalizations and other complications is not so much the issue of response, but how long it lasts."

Whom and when to treat

Invited discussant Dr. Ezra Cohen, codirector of the head and neck cancer program at the University of Chicago Comprehensive Cancer Center, said not all iodine-refractory patients need treatment, noting that at 400 days, 25% of placebo-treated patients did not progress in DECISION.

The real question going forward is not whether all refractory differentiated thyroid cancer patients should receive sorafenib, but whom and when to treat, he said. Factors that will come into play are whether the patient is symptomatic, the location of the disease and whether that location will portend the onset of symptoms in the near future, and the growth rate of their anatomic disease.

"What you don’t see on this list is the change in chemical factors, and that is specifically thyroid globulin," Dr. Cohen said. "The rise in thyroid globulin, while often important to patients, in my opinion should not be used as a criterion to initiate therapy."

He pointed out that other vascular endothelial growth factor (VEGF) receptor inhibitors are currently being evaluated in iodine-refractory differentiated thyroid cancer, including the ongoing phase III trial of lenvatinib (NCT01321554). "If I had to guess, it will reinforce the data we just saw with sorafenib," he added.

Finally, Dr. Cohen said clinicians are already seeing a wave of patients in the clinic who are refractory to VEGF inhibitors, and that this emerging entity needs to be addressed and patients encouraged to enter clinical trials.

During a press briefing at the meeting, Dr. Gregory A. Masters, of the Helen F. Graham Cancer Center in Newark, Del., told reporters that apart from entering patients in clinical trials, there are no good options for patients who progress.

"Now we have an option where we know that we can prolong progression-free survival, and I think using this for our patients will become a very attractive option and I think, yes, it will become the standard of care," he said.

DECISION was funded by Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals. Dr. Brose reported consulting fees, honoraria, and research funding from these companies. Dr. Cohen disclosed relationships with other companies.

pwendling@frontlinemedcom.com

CHICAGO – The long wait for a new medical therapy for advanced radioactive-refractory thyroid cancer is drawing to a close.

Twice-daily oral sorafenib (Nexavar) nearly doubled the median time to disease progression from 5.8 months with placebo to 10.8 months (hazard ratio, 0.587; P less than .0001) among 417 patients in the double-blind, international phase III DECISION study.

The benefit of sorafenib on this primary endpoint was seen across all patient characteristics, including age, histology, and geographic region, principal investigator Dr. Marcia S. Brose said during the plenary session at the annual meeting of the American Society of Clinical Oncology.

Patrice Wendling/IMNG Medical Media

Median overall survival has not been reached for either arm, and will be strongly affected by the 71% of controls who crossed over to open-label treatment with the multikinase inhibitor.

No standard therapy exists for the 5%-15% of patients with thyroid cancer who are refractory to standard treatment with surgery and radioactive iodine (RAI). Doxorubicin (Adriamycin) chemotherapy was approved some 30 years ago, but it is ineffective and toxic.

"Sorafenib is a potential new treatment option for patients with locally advanced or metastatic radioactive-refractory differentiated thyroid cancer," said Dr. Brose, director of thyroid cancer therapeutics and head and neck clinical trials at the University of Pennsylvania, Philadelphia.

Approval sought in U.S. and abroad

DECISION (Study of sorafenib in locally advanced or metastatic patients with radioactive iodine refractory thyroid cancer) is the first phase III study to demonstrate treatment efficacy in this setting. Based on its results, a supplemental New Drug Application will be submitted for sorafenib by midyear in the United States, with global submissions to follow, according to study sponsors Bayer Healthcare Pharmaceuticals and Onyx Pharmaceuticals. The drug is already approved in the United States for advanced renal and liver cancer.

DECISION involved 417 patients in the United States, Europe, or Asia who had locally advanced or metastatic RAI-refractory differentiated thyroid cancer that had progressed within the previous 14 months and had received no prior chemotherapy, targeted therapy, or thalidomide. Patients received twice-daily sorafenib 400 mg or placebo. The majority had distant metastases (96%), 66% had papillary histology, and 61% had an ECOG performance status of 0. Their median age was 63 years.

Sorafenib did not induce any complete responses. Partial responses, defined by at least a 30% reduction in tumor size, occurred in 12.2% of sorafenib patients vs. 0.5% of controls, and lasted for a median of 10.2 months, Dr. Brose said. An additional 42% of patients experienced stable disease for more than 6 months, resulting in a disease control rate of 54% in the sorafenib arm vs. 34% in the placebo arm.

In all, 73% of sorafenib-treated patients had some tumor shrinkage, compared with 27% of placebo-treated patients, and this was often sufficient to relieve symptoms, she said.

It would have been nice to see more partial responses, but all responses were clinically meaningful, Dr. Brose said in an interview.

"Unlike other cancers, what’s interesting is that these patients can have 100 nodules in their chest and actually experience very few symptoms, but what will kill them is when those grow," she said. "So the more clinically important number that is going to prevent the hospitalizations and other complications is not so much the issue of response, but how long it lasts."

Whom and when to treat

Invited discussant Dr. Ezra Cohen, codirector of the head and neck cancer program at the University of Chicago Comprehensive Cancer Center, said not all iodine-refractory patients need treatment, noting that at 400 days, 25% of placebo-treated patients did not progress in DECISION.

The real question going forward is not whether all refractory differentiated thyroid cancer patients should receive sorafenib, but whom and when to treat, he said. Factors that will come into play are whether the patient is symptomatic, the location of the disease and whether that location will portend the onset of symptoms in the near future, and the growth rate of their anatomic disease.

"What you don’t see on this list is the change in chemical factors, and that is specifically thyroid globulin," Dr. Cohen said. "The rise in thyroid globulin, while often important to patients, in my opinion should not be used as a criterion to initiate therapy."

He pointed out that other vascular endothelial growth factor (VEGF) receptor inhibitors are currently being evaluated in iodine-refractory differentiated thyroid cancer, including the ongoing phase III trial of lenvatinib (NCT01321554). "If I had to guess, it will reinforce the data we just saw with sorafenib," he added.

Finally, Dr. Cohen said clinicians are already seeing a wave of patients in the clinic who are refractory to VEGF inhibitors, and that this emerging entity needs to be addressed and patients encouraged to enter clinical trials.

During a press briefing at the meeting, Dr. Gregory A. Masters, of the Helen F. Graham Cancer Center in Newark, Del., told reporters that apart from entering patients in clinical trials, there are no good options for patients who progress.

"Now we have an option where we know that we can prolong progression-free survival, and I think using this for our patients will become a very attractive option and I think, yes, it will become the standard of care," he said.

DECISION was funded by Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals. Dr. Brose reported consulting fees, honoraria, and research funding from these companies. Dr. Cohen disclosed relationships with other companies.

pwendling@frontlinemedcom.com

CHICAGO – The long wait for a new medical therapy for advanced radioactive-refractory thyroid cancer is drawing to a close.

Twice-daily oral sorafenib (Nexavar) nearly doubled the median time to disease progression from 5.8 months with placebo to 10.8 months (hazard ratio, 0.587; P less than .0001) among 417 patients in the double-blind, international phase III DECISION study.

The benefit of sorafenib on this primary endpoint was seen across all patient characteristics, including age, histology, and geographic region, principal investigator Dr. Marcia S. Brose said during the plenary session at the annual meeting of the American Society of Clinical Oncology.

Patrice Wendling/IMNG Medical Media

Median overall survival has not been reached for either arm, and will be strongly affected by the 71% of controls who crossed over to open-label treatment with the multikinase inhibitor.

No standard therapy exists for the 5%-15% of patients with thyroid cancer who are refractory to standard treatment with surgery and radioactive iodine (RAI). Doxorubicin (Adriamycin) chemotherapy was approved some 30 years ago, but it is ineffective and toxic.

"Sorafenib is a potential new treatment option for patients with locally advanced or metastatic radioactive-refractory differentiated thyroid cancer," said Dr. Brose, director of thyroid cancer therapeutics and head and neck clinical trials at the University of Pennsylvania, Philadelphia.

Approval sought in U.S. and abroad

DECISION (Study of sorafenib in locally advanced or metastatic patients with radioactive iodine refractory thyroid cancer) is the first phase III study to demonstrate treatment efficacy in this setting. Based on its results, a supplemental New Drug Application will be submitted for sorafenib by midyear in the United States, with global submissions to follow, according to study sponsors Bayer Healthcare Pharmaceuticals and Onyx Pharmaceuticals. The drug is already approved in the United States for advanced renal and liver cancer.

DECISION involved 417 patients in the United States, Europe, or Asia who had locally advanced or metastatic RAI-refractory differentiated thyroid cancer that had progressed within the previous 14 months and had received no prior chemotherapy, targeted therapy, or thalidomide. Patients received twice-daily sorafenib 400 mg or placebo. The majority had distant metastases (96%), 66% had papillary histology, and 61% had an ECOG performance status of 0. Their median age was 63 years.

Sorafenib did not induce any complete responses. Partial responses, defined by at least a 30% reduction in tumor size, occurred in 12.2% of sorafenib patients vs. 0.5% of controls, and lasted for a median of 10.2 months, Dr. Brose said. An additional 42% of patients experienced stable disease for more than 6 months, resulting in a disease control rate of 54% in the sorafenib arm vs. 34% in the placebo arm.

In all, 73% of sorafenib-treated patients had some tumor shrinkage, compared with 27% of placebo-treated patients, and this was often sufficient to relieve symptoms, she said.

It would have been nice to see more partial responses, but all responses were clinically meaningful, Dr. Brose said in an interview.

"Unlike other cancers, what’s interesting is that these patients can have 100 nodules in their chest and actually experience very few symptoms, but what will kill them is when those grow," she said. "So the more clinically important number that is going to prevent the hospitalizations and other complications is not so much the issue of response, but how long it lasts."

Whom and when to treat

Invited discussant Dr. Ezra Cohen, codirector of the head and neck cancer program at the University of Chicago Comprehensive Cancer Center, said not all iodine-refractory patients need treatment, noting that at 400 days, 25% of placebo-treated patients did not progress in DECISION.

The real question going forward is not whether all refractory differentiated thyroid cancer patients should receive sorafenib, but whom and when to treat, he said. Factors that will come into play are whether the patient is symptomatic, the location of the disease and whether that location will portend the onset of symptoms in the near future, and the growth rate of their anatomic disease.

"What you don’t see on this list is the change in chemical factors, and that is specifically thyroid globulin," Dr. Cohen said. "The rise in thyroid globulin, while often important to patients, in my opinion should not be used as a criterion to initiate therapy."

He pointed out that other vascular endothelial growth factor (VEGF) receptor inhibitors are currently being evaluated in iodine-refractory differentiated thyroid cancer, including the ongoing phase III trial of lenvatinib (NCT01321554). "If I had to guess, it will reinforce the data we just saw with sorafenib," he added.

Finally, Dr. Cohen said clinicians are already seeing a wave of patients in the clinic who are refractory to VEGF inhibitors, and that this emerging entity needs to be addressed and patients encouraged to enter clinical trials.

During a press briefing at the meeting, Dr. Gregory A. Masters, of the Helen F. Graham Cancer Center in Newark, Del., told reporters that apart from entering patients in clinical trials, there are no good options for patients who progress.

"Now we have an option where we know that we can prolong progression-free survival, and I think using this for our patients will become a very attractive option and I think, yes, it will become the standard of care," he said.

DECISION was funded by Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals. Dr. Brose reported consulting fees, honoraria, and research funding from these companies. Dr. Cohen disclosed relationships with other companies.

pwendling@frontlinemedcom.com

A new practice guideline released at the American Urological Association annual meeting presents the clinical framework to help weigh the risks and benefits of providing adjuvant and salvage radiation therapy after prostatectomy.

"There is now a document that guides us in offering the best clinical practices for anyone who undergoes radical prostatectomy regarding their follow-up care with radiotherapy," said Dr. Richard K. Valicenti of the department of radiation oncology at the University of California, Davis.

One practice standard in the guideline advises physicians to offer adjuvant radiotherapy to patients with adverse pathologic findings at prostatectomy, because studies have shown that this therapy can result in reductions in prostate-specific antigen (PSA) recurrence, local recurrence, and clinical progression. The adverse findings that would warrant this therapy include seminal vesicle invasion, positive surgical margins, or extraprostatic extension.

"The data are overwhelmingly consistent that it [radiotherapy] will improve on tumor control rates, as well as progression-free survival," Dr. Valicenti said, adding that these patients should also experience improved quality of life.

In addition to the above practice standard, the guideline, issued jointly by the American Society for Radiation Oncology (ASTRO) and the American Urological Association (AUA), made the following recommendations:

• Inform patients with localized prostate cancer considering radical prostatectomy about the possibility that the pathologic findings will predict a higher risk of cancer recurrence.

• Advise patients with adverse pathologic findings, including seminal vesicle invasion, positive surgical margins, and extraprostatic extension, that adjuvant radiation therapy compared with radical prostatectomy only reduces the risk of PSA recurrence, local recurrence, and clinical progression of cancer;

• Warn patients that they are a higher risk of developing metastatic prostate cancer or death from the disease if there is a PSA recurrence after surgery;

• Define biochemical recurrence as a detectable or rising PSA value after surgery that is greater than or equal to 0.2 ng/mL with a second confirmatory level greater than or equal to 0.2 ng/mL.

• Consider a restaging evaluation in patients with a PSA recurrence.

• Offer salvage radiation therapy to patients with PSA or local recurrence after radical prostatectomy in whom there is no evidence of distant metastatic disease.

• Inform patients that the effectiveness of radiation therapy for PSA recurrence is greatest when given at lower levels of PSA. and

• Inform patients that in addition to the benefits of controlling disease recurrence, radiation therapy could produce possible short- and long-term urinary, bowel, and sexual side effects.

Before recommending adjuvant or salvage radiotherapy, "look at the patients’ biological information obtained from the radical prostatectomy specimen, and balance that with the overall health status of the patients [and] concerns about certain aspects of quality of life, whether it be sexual activity or urinary function. They also need to balance that with any other medical conditions or previous treatments that would preclude the use of radiation therapy," Dr. Valicenti said.

"The Adjuvant and Salvage Radiotherapy After Prostatectomy: ASTRO/AUA Guideline" is a comprehensive review of 324 research articles on patients with detectable and undetectable PSA levels, toxicity, optimal imaging strategies, and the impact on quality of life to determine the appropriateness of radiation therapy in patients suspected of recurrence. Only studies in which PSA data were provided for at least 75% of patients were included in the guideline. The panel was led by Dr. Valicenti and Dr. Ian M. Thompson of the University of Texas Health Science Center.

The guideline is available at www.redjournal.org and www.auanet.org.

Dr. Valicenti reported no relevant disclosures.

A new practice guideline released at the American Urological Association annual meeting presents the clinical framework to help weigh the risks and benefits of providing adjuvant and salvage radiation therapy after prostatectomy.

"There is now a document that guides us in offering the best clinical practices for anyone who undergoes radical prostatectomy regarding their follow-up care with radiotherapy," said Dr. Richard K. Valicenti of the department of radiation oncology at the University of California, Davis.

One practice standard in the guideline advises physicians to offer adjuvant radiotherapy to patients with adverse pathologic findings at prostatectomy, because studies have shown that this therapy can result in reductions in prostate-specific antigen (PSA) recurrence, local recurrence, and clinical progression. The adverse findings that would warrant this therapy include seminal vesicle invasion, positive surgical margins, or extraprostatic extension.

"The data are overwhelmingly consistent that it [radiotherapy] will improve on tumor control rates, as well as progression-free survival," Dr. Valicenti said, adding that these patients should also experience improved quality of life.

In addition to the above practice standard, the guideline, issued jointly by the American Society for Radiation Oncology (ASTRO) and the American Urological Association (AUA), made the following recommendations:

• Inform patients with localized prostate cancer considering radical prostatectomy about the possibility that the pathologic findings will predict a higher risk of cancer recurrence.

• Advise patients with adverse pathologic findings, including seminal vesicle invasion, positive surgical margins, and extraprostatic extension, that adjuvant radiation therapy compared with radical prostatectomy only reduces the risk of PSA recurrence, local recurrence, and clinical progression of cancer;

• Warn patients that they are a higher risk of developing metastatic prostate cancer or death from the disease if there is a PSA recurrence after surgery;

• Define biochemical recurrence as a detectable or rising PSA value after surgery that is greater than or equal to 0.2 ng/mL with a second confirmatory level greater than or equal to 0.2 ng/mL.

• Consider a restaging evaluation in patients with a PSA recurrence.

• Offer salvage radiation therapy to patients with PSA or local recurrence after radical prostatectomy in whom there is no evidence of distant metastatic disease.

• Inform patients that the effectiveness of radiation therapy for PSA recurrence is greatest when given at lower levels of PSA. and

• Inform patients that in addition to the benefits of controlling disease recurrence, radiation therapy could produce possible short- and long-term urinary, bowel, and sexual side effects.

Before recommending adjuvant or salvage radiotherapy, "look at the patients’ biological information obtained from the radical prostatectomy specimen, and balance that with the overall health status of the patients [and] concerns about certain aspects of quality of life, whether it be sexual activity or urinary function. They also need to balance that with any other medical conditions or previous treatments that would preclude the use of radiation therapy," Dr. Valicenti said.

"The Adjuvant and Salvage Radiotherapy After Prostatectomy: ASTRO/AUA Guideline" is a comprehensive review of 324 research articles on patients with detectable and undetectable PSA levels, toxicity, optimal imaging strategies, and the impact on quality of life to determine the appropriateness of radiation therapy in patients suspected of recurrence. Only studies in which PSA data were provided for at least 75% of patients were included in the guideline. The panel was led by Dr. Valicenti and Dr. Ian M. Thompson of the University of Texas Health Science Center.

The guideline is available at www.redjournal.org and www.auanet.org.

Dr. Valicenti reported no relevant disclosures.

A new practice guideline released at the American Urological Association annual meeting presents the clinical framework to help weigh the risks and benefits of providing adjuvant and salvage radiation therapy after prostatectomy.

"There is now a document that guides us in offering the best clinical practices for anyone who undergoes radical prostatectomy regarding their follow-up care with radiotherapy," said Dr. Richard K. Valicenti of the department of radiation oncology at the University of California, Davis.

One practice standard in the guideline advises physicians to offer adjuvant radiotherapy to patients with adverse pathologic findings at prostatectomy, because studies have shown that this therapy can result in reductions in prostate-specific antigen (PSA) recurrence, local recurrence, and clinical progression. The adverse findings that would warrant this therapy include seminal vesicle invasion, positive surgical margins, or extraprostatic extension.

"The data are overwhelmingly consistent that it [radiotherapy] will improve on tumor control rates, as well as progression-free survival," Dr. Valicenti said, adding that these patients should also experience improved quality of life.

In addition to the above practice standard, the guideline, issued jointly by the American Society for Radiation Oncology (ASTRO) and the American Urological Association (AUA), made the following recommendations:

• Inform patients with localized prostate cancer considering radical prostatectomy about the possibility that the pathologic findings will predict a higher risk of cancer recurrence.

• Advise patients with adverse pathologic findings, including seminal vesicle invasion, positive surgical margins, and extraprostatic extension, that adjuvant radiation therapy compared with radical prostatectomy only reduces the risk of PSA recurrence, local recurrence, and clinical progression of cancer;

• Warn patients that they are a higher risk of developing metastatic prostate cancer or death from the disease if there is a PSA recurrence after surgery;

• Define biochemical recurrence as a detectable or rising PSA value after surgery that is greater than or equal to 0.2 ng/mL with a second confirmatory level greater than or equal to 0.2 ng/mL.

• Consider a restaging evaluation in patients with a PSA recurrence.

• Offer salvage radiation therapy to patients with PSA or local recurrence after radical prostatectomy in whom there is no evidence of distant metastatic disease.

• Inform patients that the effectiveness of radiation therapy for PSA recurrence is greatest when given at lower levels of PSA. and

• Inform patients that in addition to the benefits of controlling disease recurrence, radiation therapy could produce possible short- and long-term urinary, bowel, and sexual side effects.

Before recommending adjuvant or salvage radiotherapy, "look at the patients’ biological information obtained from the radical prostatectomy specimen, and balance that with the overall health status of the patients [and] concerns about certain aspects of quality of life, whether it be sexual activity or urinary function. They also need to balance that with any other medical conditions or previous treatments that would preclude the use of radiation therapy," Dr. Valicenti said.

"The Adjuvant and Salvage Radiotherapy After Prostatectomy: ASTRO/AUA Guideline" is a comprehensive review of 324 research articles on patients with detectable and undetectable PSA levels, toxicity, optimal imaging strategies, and the impact on quality of life to determine the appropriateness of radiation therapy in patients suspected of recurrence. Only studies in which PSA data were provided for at least 75% of patients were included in the guideline. The panel was led by Dr. Valicenti and Dr. Ian M. Thompson of the University of Texas Health Science Center.

The guideline is available at www.redjournal.org and www.auanet.org.

Dr. Valicenti reported no relevant disclosures.