Kate Goodrich, MD, medical officer for the Office of the Assistant Secretary for Planning and Evaluation (ASPE) in the U.S. Department of Health and Human Services (HHS), says she frequently is surprised at how much her work as an academic hospitalist is valued in her current role in planning health policy and overseeing government quality and comparative-effectiveness initiatives.

Dr. Goodrich was director of the Division of Hospital Medicine at George Washington University Medical Center in Washington, D.C., before an abiding interest in policy development led her to seek a Robert Wood Johnson Clinical Scholars fellowship to Yale University, which started in 2008. From there, she landed a government position in March 2010.

"I really loved hospital medicine, but I became more aware of the issues the country grapples with, such as poor access to primary care for large numbers of patients," she says. "I became interested in researching those questions even before I really knew what health services research was. I found myself drawn like a magnet to the policy stuff, especially during the 2008 election, with everything policy-related in the news. It finally dawned on me that if I love this so much, why not see if I can make it a career?"

During a summer internship at HHS in 2009, she enjoyed the mentorship of another hospitalist leader, Patrick Conway, MD, MSc, SFHM, who then held the job she now holds and currently is chief medical officer for the Centers for Medicare & Medicaid Services. Given all of the focus on health care reform, Dr. Goodrich says, this is the best of times to be working for the government, "especially for someone who strongly feels that health reform was needed."

She recommends ways other hospitalists can learn more about health policy and participate in its development:

• Start by becoming involved in local quality initiatives in the hospital and the community.

• Join SHM's Public Policy Committee.

• Follow health policy blogs, websites, and other resources offered by HHS, SHM, and private groups, such as the Commonwealth Fund.

• Look into the health policy fellowships or training opportunities offered by a number of national organizations, such as the Robert Wood Johnson Foundation.

Kate Goodrich, MD, medical officer for the Office of the Assistant Secretary for Planning and Evaluation (ASPE) in the U.S. Department of Health and Human Services (HHS), says she frequently is surprised at how much her work as an academic hospitalist is valued in her current role in planning health policy and overseeing government quality and comparative-effectiveness initiatives.

Dr. Goodrich was director of the Division of Hospital Medicine at George Washington University Medical Center in Washington, D.C., before an abiding interest in policy development led her to seek a Robert Wood Johnson Clinical Scholars fellowship to Yale University, which started in 2008. From there, she landed a government position in March 2010.

"I really loved hospital medicine, but I became more aware of the issues the country grapples with, such as poor access to primary care for large numbers of patients," she says. "I became interested in researching those questions even before I really knew what health services research was. I found myself drawn like a magnet to the policy stuff, especially during the 2008 election, with everything policy-related in the news. It finally dawned on me that if I love this so much, why not see if I can make it a career?"

During a summer internship at HHS in 2009, she enjoyed the mentorship of another hospitalist leader, Patrick Conway, MD, MSc, SFHM, who then held the job she now holds and currently is chief medical officer for the Centers for Medicare & Medicaid Services. Given all of the focus on health care reform, Dr. Goodrich says, this is the best of times to be working for the government, "especially for someone who strongly feels that health reform was needed."

She recommends ways other hospitalists can learn more about health policy and participate in its development:

• Start by becoming involved in local quality initiatives in the hospital and the community.

• Join SHM's Public Policy Committee.

• Follow health policy blogs, websites, and other resources offered by HHS, SHM, and private groups, such as the Commonwealth Fund.

• Look into the health policy fellowships or training opportunities offered by a number of national organizations, such as the Robert Wood Johnson Foundation.

Kate Goodrich, MD, medical officer for the Office of the Assistant Secretary for Planning and Evaluation (ASPE) in the U.S. Department of Health and Human Services (HHS), says she frequently is surprised at how much her work as an academic hospitalist is valued in her current role in planning health policy and overseeing government quality and comparative-effectiveness initiatives.

Dr. Goodrich was director of the Division of Hospital Medicine at George Washington University Medical Center in Washington, D.C., before an abiding interest in policy development led her to seek a Robert Wood Johnson Clinical Scholars fellowship to Yale University, which started in 2008. From there, she landed a government position in March 2010.

"I really loved hospital medicine, but I became more aware of the issues the country grapples with, such as poor access to primary care for large numbers of patients," she says. "I became interested in researching those questions even before I really knew what health services research was. I found myself drawn like a magnet to the policy stuff, especially during the 2008 election, with everything policy-related in the news. It finally dawned on me that if I love this so much, why not see if I can make it a career?"

During a summer internship at HHS in 2009, she enjoyed the mentorship of another hospitalist leader, Patrick Conway, MD, MSc, SFHM, who then held the job she now holds and currently is chief medical officer for the Centers for Medicare & Medicaid Services. Given all of the focus on health care reform, Dr. Goodrich says, this is the best of times to be working for the government, "especially for someone who strongly feels that health reform was needed."

She recommends ways other hospitalists can learn more about health policy and participate in its development:

• Start by becoming involved in local quality initiatives in the hospital and the community.

• Join SHM's Public Policy Committee.

• Follow health policy blogs, websites, and other resources offered by HHS, SHM, and private groups, such as the Commonwealth Fund.

• Look into the health policy fellowships or training opportunities offered by a number of national organizations, such as the Robert Wood Johnson Foundation.

AMSTERDAM  – Quantifying the amount of epidermal growth factor receptor in a patient’s advanced nonsmall cell lung cancer tumor appeared to identify the tumors that best responded to treatment with cetuximab in an analysis of 1,125 patients enrolled in a key multicenter treatment trial.

The analysis was a follow-up to the positive Cetuximab Plus Chemotherapy in Patients with Non–Small Cell Lung Cancer (FLEX) study, which showed a benefit from the addition of cetuximab (Erbitux) to platinum-based therapy (Lancet 2009;373:1525-31).

Division of the study population into 31% with a high level of epidermal growth factor receptor (EGFR) expression on the surface of tumor cells and 69% with lower expression identified a patient subgroup, the high expressors, that responded best to cetuximab with no increased toxicity, Dr. Robert Pirker reported at the World Conference on Lung Cancer, sponsored by the International Association for the Study of Lung Cancer.

"The data clearly show that EGFR is a predictive biomarker because in high-EGFR cancers cetuximab changed survival, reduced the hazard ratio to 0.73 [compared with patients not getting cetuximab], but in patients with lower EGFR, cetuximab added nothing to survival," said Dr. Pirker, professor and program director for lung cancer at the Medical University of Vienna.

"We increase efficacy without increasing toxicity, improving the benefit-to-risk ratio. This is a major step forward toward personalized medicine, especially for patients with high EGFR, about a third of patients with advanced disease," he said.

Because the FLEX study’s prespecified goals included analysis of the link between EGFR density and cetuximab response, the new findings warrant immediate application to practice, according to Dr. Pirker. "I believe this is such a significant improvement in survival that we’ve never seen before that we should be able to provide it to our patients," he said.

Future work should examine the potential role of other drugs that affect EGFR activity (the tyrosine kinase inhibitors such as erlotinib and gefitinib) and also the potential role of cetuximab in high EGFR expressors with earlier-stage lung cancer, he added.

But while other lung cancer specialists saw this finding as an exciting new opportunity for directing EGFR-based treatment to the patients who stand to benefit most, they also called for caution in using EGFR quantification in routine practice.

"It needs prospective validation before it can be standard of care," commented Dr. Roy S. Herbst, chief of medical oncology at the Yale Cancer Center in New Haven, Conn. "It’s very intriguing and makes sense that the amount of receptor will make a difference for cetuximab, but it needs to be tested prospectively because they determined the cutoff retrospectively. It’s always dangerous to use a cutoff determined post hoc, because it becomes a self-fulfilling prophesy. It needs to be studied in a validation set. But it gives new hope for the potential use" of cetuximab and other drugs aimed at EGFR function, Dr. Herbst said in an interview.

"These findings from a post hoc analysis for the selected cutoff are extremely interesting and important, but it needs prospective validation," agreed Dr. Giorgio V. Scagliotti, professor of respiratory medicine at the University of Torino, Italy.

The EGFR scoring formula that Dr. Pirker and his associates developed used a commercially available immunohistochemistry staining kit, made by DAKO. Scoring involved rating the staining intensity of each stained cell in a tumor specimen on a scale of 0-3, where 0 is no staining and 3 is the highest level of staining, and then multiplying each score level by the percent of cells in the specimen with that score. This results in a potential score range of 0 (100% of cells have a score of 0) to 300 (100% of cells have a score of 3).

In their review of the FLEX data, the researchers found that 345 (31%) of patients had tumors with a score of at least 200, the cutoff they selected post hoc for a high level of EGFR expression, and the other 776 (69%) had a low score, less than 200.

With this method distinguishing tumors with high and low levels of EGFR expression, the 345 patients in the high category had a 0.73 hazard ratio for mortality when treated with cetuximab plus chemotherapy (cisplatin plus vinorelbine), compared with patients treated with chemotherapy only (P = .011). This appeared to improve on the reduced mortality seen with cetuximab treatment in the entire study of 1,125 patients, which produced a hazard ratio of 0.87 (P = .044). In the 776 patients with lower EGFR expression, the addition of cetuximab led to no change in survival compared with patients who received the control treatment regimen.

Cetuximab’s enhanced efficacy in high EGFR expressors occurred in both the 135 patients with an adenocarcinoma, and in the 144 patients with a squamous cell carcinoma. Among the high expressors, cetuximab also had significantly better performance measures by tumor response rate, with a twofold higher response rate with cetuximab compared with controls (P = .002), and by time-to-treatment-failure, with a statistically significant, average 22% drop in this time (P = .026) with cetuximab compared with controls.

But focusing on high expressors did not result in a significantly improved duration of progression-free survival. The analysis also showed no increased rate of safety issues in the high expressors who received cetuximab, including no increased rate of skin or subcutaneous disorders.

The FLEX study was funded by Merck, which markets cetuximab (Erbitux) outside the United States. Dr. Pirker disclosed relationships with seven companies, including Merck and Eli Lilly, which markets cetuximab in the United States. Dr. Herbst also cited ties to numerous companies, including ImClone, a Lilly subsidiary that developed cetuximab. Dr. Scagliotti had relationships with four companies, including Lilly.

AMSTERDAM  – Quantifying the amount of epidermal growth factor receptor in a patient’s advanced nonsmall cell lung cancer tumor appeared to identify the tumors that best responded to treatment with cetuximab in an analysis of 1,125 patients enrolled in a key multicenter treatment trial.

The analysis was a follow-up to the positive Cetuximab Plus Chemotherapy in Patients with Non–Small Cell Lung Cancer (FLEX) study, which showed a benefit from the addition of cetuximab (Erbitux) to platinum-based therapy (Lancet 2009;373:1525-31).

Division of the study population into 31% with a high level of epidermal growth factor receptor (EGFR) expression on the surface of tumor cells and 69% with lower expression identified a patient subgroup, the high expressors, that responded best to cetuximab with no increased toxicity, Dr. Robert Pirker reported at the World Conference on Lung Cancer, sponsored by the International Association for the Study of Lung Cancer.

"The data clearly show that EGFR is a predictive biomarker because in high-EGFR cancers cetuximab changed survival, reduced the hazard ratio to 0.73 [compared with patients not getting cetuximab], but in patients with lower EGFR, cetuximab added nothing to survival," said Dr. Pirker, professor and program director for lung cancer at the Medical University of Vienna.

"We increase efficacy without increasing toxicity, improving the benefit-to-risk ratio. This is a major step forward toward personalized medicine, especially for patients with high EGFR, about a third of patients with advanced disease," he said.

Because the FLEX study’s prespecified goals included analysis of the link between EGFR density and cetuximab response, the new findings warrant immediate application to practice, according to Dr. Pirker. "I believe this is such a significant improvement in survival that we’ve never seen before that we should be able to provide it to our patients," he said.

Future work should examine the potential role of other drugs that affect EGFR activity (the tyrosine kinase inhibitors such as erlotinib and gefitinib) and also the potential role of cetuximab in high EGFR expressors with earlier-stage lung cancer, he added.

But while other lung cancer specialists saw this finding as an exciting new opportunity for directing EGFR-based treatment to the patients who stand to benefit most, they also called for caution in using EGFR quantification in routine practice.

"It needs prospective validation before it can be standard of care," commented Dr. Roy S. Herbst, chief of medical oncology at the Yale Cancer Center in New Haven, Conn. "It’s very intriguing and makes sense that the amount of receptor will make a difference for cetuximab, but it needs to be tested prospectively because they determined the cutoff retrospectively. It’s always dangerous to use a cutoff determined post hoc, because it becomes a self-fulfilling prophesy. It needs to be studied in a validation set. But it gives new hope for the potential use" of cetuximab and other drugs aimed at EGFR function, Dr. Herbst said in an interview.

"These findings from a post hoc analysis for the selected cutoff are extremely interesting and important, but it needs prospective validation," agreed Dr. Giorgio V. Scagliotti, professor of respiratory medicine at the University of Torino, Italy.

The EGFR scoring formula that Dr. Pirker and his associates developed used a commercially available immunohistochemistry staining kit, made by DAKO. Scoring involved rating the staining intensity of each stained cell in a tumor specimen on a scale of 0-3, where 0 is no staining and 3 is the highest level of staining, and then multiplying each score level by the percent of cells in the specimen with that score. This results in a potential score range of 0 (100% of cells have a score of 0) to 300 (100% of cells have a score of 3).

In their review of the FLEX data, the researchers found that 345 (31%) of patients had tumors with a score of at least 200, the cutoff they selected post hoc for a high level of EGFR expression, and the other 776 (69%) had a low score, less than 200.

With this method distinguishing tumors with high and low levels of EGFR expression, the 345 patients in the high category had a 0.73 hazard ratio for mortality when treated with cetuximab plus chemotherapy (cisplatin plus vinorelbine), compared with patients treated with chemotherapy only (P = .011). This appeared to improve on the reduced mortality seen with cetuximab treatment in the entire study of 1,125 patients, which produced a hazard ratio of 0.87 (P = .044). In the 776 patients with lower EGFR expression, the addition of cetuximab led to no change in survival compared with patients who received the control treatment regimen.

Cetuximab’s enhanced efficacy in high EGFR expressors occurred in both the 135 patients with an adenocarcinoma, and in the 144 patients with a squamous cell carcinoma. Among the high expressors, cetuximab also had significantly better performance measures by tumor response rate, with a twofold higher response rate with cetuximab compared with controls (P = .002), and by time-to-treatment-failure, with a statistically significant, average 22% drop in this time (P = .026) with cetuximab compared with controls.

But focusing on high expressors did not result in a significantly improved duration of progression-free survival. The analysis also showed no increased rate of safety issues in the high expressors who received cetuximab, including no increased rate of skin or subcutaneous disorders.

The FLEX study was funded by Merck, which markets cetuximab (Erbitux) outside the United States. Dr. Pirker disclosed relationships with seven companies, including Merck and Eli Lilly, which markets cetuximab in the United States. Dr. Herbst also cited ties to numerous companies, including ImClone, a Lilly subsidiary that developed cetuximab. Dr. Scagliotti had relationships with four companies, including Lilly.

AMSTERDAM  – Quantifying the amount of epidermal growth factor receptor in a patient’s advanced nonsmall cell lung cancer tumor appeared to identify the tumors that best responded to treatment with cetuximab in an analysis of 1,125 patients enrolled in a key multicenter treatment trial.

The analysis was a follow-up to the positive Cetuximab Plus Chemotherapy in Patients with Non–Small Cell Lung Cancer (FLEX) study, which showed a benefit from the addition of cetuximab (Erbitux) to platinum-based therapy (Lancet 2009;373:1525-31).

Division of the study population into 31% with a high level of epidermal growth factor receptor (EGFR) expression on the surface of tumor cells and 69% with lower expression identified a patient subgroup, the high expressors, that responded best to cetuximab with no increased toxicity, Dr. Robert Pirker reported at the World Conference on Lung Cancer, sponsored by the International Association for the Study of Lung Cancer.

"The data clearly show that EGFR is a predictive biomarker because in high-EGFR cancers cetuximab changed survival, reduced the hazard ratio to 0.73 [compared with patients not getting cetuximab], but in patients with lower EGFR, cetuximab added nothing to survival," said Dr. Pirker, professor and program director for lung cancer at the Medical University of Vienna.

"We increase efficacy without increasing toxicity, improving the benefit-to-risk ratio. This is a major step forward toward personalized medicine, especially for patients with high EGFR, about a third of patients with advanced disease," he said.

Because the FLEX study’s prespecified goals included analysis of the link between EGFR density and cetuximab response, the new findings warrant immediate application to practice, according to Dr. Pirker. "I believe this is such a significant improvement in survival that we’ve never seen before that we should be able to provide it to our patients," he said.

Future work should examine the potential role of other drugs that affect EGFR activity (the tyrosine kinase inhibitors such as erlotinib and gefitinib) and also the potential role of cetuximab in high EGFR expressors with earlier-stage lung cancer, he added.

But while other lung cancer specialists saw this finding as an exciting new opportunity for directing EGFR-based treatment to the patients who stand to benefit most, they also called for caution in using EGFR quantification in routine practice.

"It needs prospective validation before it can be standard of care," commented Dr. Roy S. Herbst, chief of medical oncology at the Yale Cancer Center in New Haven, Conn. "It’s very intriguing and makes sense that the amount of receptor will make a difference for cetuximab, but it needs to be tested prospectively because they determined the cutoff retrospectively. It’s always dangerous to use a cutoff determined post hoc, because it becomes a self-fulfilling prophesy. It needs to be studied in a validation set. But it gives new hope for the potential use" of cetuximab and other drugs aimed at EGFR function, Dr. Herbst said in an interview.

"These findings from a post hoc analysis for the selected cutoff are extremely interesting and important, but it needs prospective validation," agreed Dr. Giorgio V. Scagliotti, professor of respiratory medicine at the University of Torino, Italy.

The EGFR scoring formula that Dr. Pirker and his associates developed used a commercially available immunohistochemistry staining kit, made by DAKO. Scoring involved rating the staining intensity of each stained cell in a tumor specimen on a scale of 0-3, where 0 is no staining and 3 is the highest level of staining, and then multiplying each score level by the percent of cells in the specimen with that score. This results in a potential score range of 0 (100% of cells have a score of 0) to 300 (100% of cells have a score of 3).

In their review of the FLEX data, the researchers found that 345 (31%) of patients had tumors with a score of at least 200, the cutoff they selected post hoc for a high level of EGFR expression, and the other 776 (69%) had a low score, less than 200.

With this method distinguishing tumors with high and low levels of EGFR expression, the 345 patients in the high category had a 0.73 hazard ratio for mortality when treated with cetuximab plus chemotherapy (cisplatin plus vinorelbine), compared with patients treated with chemotherapy only (P = .011). This appeared to improve on the reduced mortality seen with cetuximab treatment in the entire study of 1,125 patients, which produced a hazard ratio of 0.87 (P = .044). In the 776 patients with lower EGFR expression, the addition of cetuximab led to no change in survival compared with patients who received the control treatment regimen.

Cetuximab’s enhanced efficacy in high EGFR expressors occurred in both the 135 patients with an adenocarcinoma, and in the 144 patients with a squamous cell carcinoma. Among the high expressors, cetuximab also had significantly better performance measures by tumor response rate, with a twofold higher response rate with cetuximab compared with controls (P = .002), and by time-to-treatment-failure, with a statistically significant, average 22% drop in this time (P = .026) with cetuximab compared with controls.

But focusing on high expressors did not result in a significantly improved duration of progression-free survival. The analysis also showed no increased rate of safety issues in the high expressors who received cetuximab, including no increased rate of skin or subcutaneous disorders.

The FLEX study was funded by Merck, which markets cetuximab (Erbitux) outside the United States. Dr. Pirker disclosed relationships with seven companies, including Merck and Eli Lilly, which markets cetuximab in the United States. Dr. Herbst also cited ties to numerous companies, including ImClone, a Lilly subsidiary that developed cetuximab. Dr. Scagliotti had relationships with four companies, including Lilly.

The US Food and Drug Administration (FDA) has approved the antiplatelet agent ticagrelor for reducing thrombotic events in patients with acute coronary syndromes.

The FDA based its decision on results of the PLATO trial, which compared ticagrelor to clopidogrel.

Some 9.8% of patients treated with ticagrelor experienced cardiovascular death, myocardial infarction, or stroke at 12 months compared to 11.7% of patients treated with clopidogrel, which amounted to a relative risk reduction of 16% (P<0.001).

The product label includes a boxed warning that aspirin doses above 100 mg per day decrease the effectiveness of the medication and should be avoided.

For more information on the approval, visit FDA.gov.

The US Food and Drug Administration (FDA) has approved the antiplatelet agent ticagrelor for reducing thrombotic events in patients with acute coronary syndromes.

The FDA based its decision on results of the PLATO trial, which compared ticagrelor to clopidogrel.

Some 9.8% of patients treated with ticagrelor experienced cardiovascular death, myocardial infarction, or stroke at 12 months compared to 11.7% of patients treated with clopidogrel, which amounted to a relative risk reduction of 16% (P<0.001).

The product label includes a boxed warning that aspirin doses above 100 mg per day decrease the effectiveness of the medication and should be avoided.

For more information on the approval, visit FDA.gov.

The US Food and Drug Administration (FDA) has approved the antiplatelet agent ticagrelor for reducing thrombotic events in patients with acute coronary syndromes.

The FDA based its decision on results of the PLATO trial, which compared ticagrelor to clopidogrel.

Some 9.8% of patients treated with ticagrelor experienced cardiovascular death, myocardial infarction, or stroke at 12 months compared to 11.7% of patients treated with clopidogrel, which amounted to a relative risk reduction of 16% (P<0.001).

The product label includes a boxed warning that aspirin doses above 100 mg per day decrease the effectiveness of the medication and should be avoided.

For more information on the approval, visit FDA.gov.

Earlier this month, the FDA approved Xarelto (rivaroxaban) to cut the risk of blood clots, DVT, and pulmonary embolism after knee and hip replacement surgery. According to one hospitalist, the drug approval represents another way to prevent blood clots on an outpatient basis.

The drug is a pill that is taken once a day. Those having knee replacements should take the medication for 12 days, and those having hip replacements should take it for 35 days, according to FDA guidelines.

"I think that it has the potential of being a game-changer," says Robert Pendleton, MD, codirector of the hospitalist program and medical director of the University Healthcare Thrombosis Service at the University of Utah Medical Center in Salt Lake City. "It definitely could turn out to be a blockbuster drug."

In a statement, Paul Chang, MD, vice president of medical affairs in internal medicine at Janssen Pharmaceuticals Inc., said, "Shorter hospital stays following hip and knee replacement surgeries have made the prevention of venous blood clots an outpatient issue, and Xarelto provides a safe and effective oral treatment option that can be easily transitioned from use in hospital to home."

The approval is the latest challenge to warfarin. It comes on the heels of the approval of Pradaxa (dabigatran) for stroke prevention in nonvalvular atrial fibrillation patients. (Updated July 21). Xarelto, however, is the only new oral anticoagulant approved for its indication.

Dr. Pendleton says the advantage of Xarelto is that it only has to be taken once a day. He said the full potential lies in the "high likelihood of subsequent indications" for the drug.

Still, this is a new drug and care has to be taken, he says.

"If it's not used appropriately in the proper patient with proper attention to renal function and drug-drug interaction," he adds, "a very promising drug could have difficulty."

Earlier this month, the FDA approved Xarelto (rivaroxaban) to cut the risk of blood clots, DVT, and pulmonary embolism after knee and hip replacement surgery. According to one hospitalist, the drug approval represents another way to prevent blood clots on an outpatient basis.

The drug is a pill that is taken once a day. Those having knee replacements should take the medication for 12 days, and those having hip replacements should take it for 35 days, according to FDA guidelines.

"I think that it has the potential of being a game-changer," says Robert Pendleton, MD, codirector of the hospitalist program and medical director of the University Healthcare Thrombosis Service at the University of Utah Medical Center in Salt Lake City. "It definitely could turn out to be a blockbuster drug."

In a statement, Paul Chang, MD, vice president of medical affairs in internal medicine at Janssen Pharmaceuticals Inc., said, "Shorter hospital stays following hip and knee replacement surgeries have made the prevention of venous blood clots an outpatient issue, and Xarelto provides a safe and effective oral treatment option that can be easily transitioned from use in hospital to home."

The approval is the latest challenge to warfarin. It comes on the heels of the approval of Pradaxa (dabigatran) for stroke prevention in nonvalvular atrial fibrillation patients. (Updated July 21). Xarelto, however, is the only new oral anticoagulant approved for its indication.

Dr. Pendleton says the advantage of Xarelto is that it only has to be taken once a day. He said the full potential lies in the "high likelihood of subsequent indications" for the drug.

Still, this is a new drug and care has to be taken, he says.

"If it's not used appropriately in the proper patient with proper attention to renal function and drug-drug interaction," he adds, "a very promising drug could have difficulty."

Earlier this month, the FDA approved Xarelto (rivaroxaban) to cut the risk of blood clots, DVT, and pulmonary embolism after knee and hip replacement surgery. According to one hospitalist, the drug approval represents another way to prevent blood clots on an outpatient basis.

The drug is a pill that is taken once a day. Those having knee replacements should take the medication for 12 days, and those having hip replacements should take it for 35 days, according to FDA guidelines.

"I think that it has the potential of being a game-changer," says Robert Pendleton, MD, codirector of the hospitalist program and medical director of the University Healthcare Thrombosis Service at the University of Utah Medical Center in Salt Lake City. "It definitely could turn out to be a blockbuster drug."

In a statement, Paul Chang, MD, vice president of medical affairs in internal medicine at Janssen Pharmaceuticals Inc., said, "Shorter hospital stays following hip and knee replacement surgeries have made the prevention of venous blood clots an outpatient issue, and Xarelto provides a safe and effective oral treatment option that can be easily transitioned from use in hospital to home."

The approval is the latest challenge to warfarin. It comes on the heels of the approval of Pradaxa (dabigatran) for stroke prevention in nonvalvular atrial fibrillation patients. (Updated July 21). Xarelto, however, is the only new oral anticoagulant approved for its indication.

Dr. Pendleton says the advantage of Xarelto is that it only has to be taken once a day. He said the full potential lies in the "high likelihood of subsequent indications" for the drug.

Still, this is a new drug and care has to be taken, he says.

"If it's not used appropriately in the proper patient with proper attention to renal function and drug-drug interaction," he adds, "a very promising drug could have difficulty."

Clinical question: What is the effect of corticosteroid therapy on survival in severe alcoholic hepatitis?

Background: Previous meta-analyses have suggested a survival benefit of corticosteroid treatment restricted only to those patients with severe alcoholic hepatitis (AH), with little or no benefit in less severe disease. Other meta-analyses, however, have questioned the efficacy in AH regardless of disease severity.

Study design: Meta-analysis of individual patient data.

Setting: Five randomized controlled trials (RCT) enrolling 418 patients.

Synopsis: Individual patient data were obtained from five RCTs comparing corticosteroid treatment with placebo (n3), enteral nutrition (n1), or an antioxidant cocktail (n1). Researchers analyzed 221 patients allocated to corticosteroid treatment and 197 allocated to noncorticosteroid treatment. Twenty-eight-day survival was higher in corticosteroid treated patients than in noncorticosteroid-treated patients (79.97% vs. 65.76%, P=0.0005). A subgroup analysis was performed according to the Lille score. Patients were classified as complete responders, partial responders, and null responders. Corticosteroids had a significant effect on 28-day survival in complete responders and in partial responders, but not in null responders (91.16% vs. 79.46% vs. 53.36%, P<0.0001)

Bottom line: Corticosteroids significantly improve 28-day survival in patients with severe alcoholic hepatitis. The survival benefit is mainly observed in patients classified as responders by the Lille model.

Citation: Mathurin P, O'Grady J, Carithers RL et al. Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis: meta-analysis of individual patient data. Gut. 2011;60(2):255-260.

For more physician reviews of HM-related research, visit our website.

Clinical question: What is the effect of corticosteroid therapy on survival in severe alcoholic hepatitis?

Background: Previous meta-analyses have suggested a survival benefit of corticosteroid treatment restricted only to those patients with severe alcoholic hepatitis (AH), with little or no benefit in less severe disease. Other meta-analyses, however, have questioned the efficacy in AH regardless of disease severity.

Study design: Meta-analysis of individual patient data.

Setting: Five randomized controlled trials (RCT) enrolling 418 patients.

Synopsis: Individual patient data were obtained from five RCTs comparing corticosteroid treatment with placebo (n3), enteral nutrition (n1), or an antioxidant cocktail (n1). Researchers analyzed 221 patients allocated to corticosteroid treatment and 197 allocated to noncorticosteroid treatment. Twenty-eight-day survival was higher in corticosteroid treated patients than in noncorticosteroid-treated patients (79.97% vs. 65.76%, P=0.0005). A subgroup analysis was performed according to the Lille score. Patients were classified as complete responders, partial responders, and null responders. Corticosteroids had a significant effect on 28-day survival in complete responders and in partial responders, but not in null responders (91.16% vs. 79.46% vs. 53.36%, P<0.0001)

Bottom line: Corticosteroids significantly improve 28-day survival in patients with severe alcoholic hepatitis. The survival benefit is mainly observed in patients classified as responders by the Lille model.

Citation: Mathurin P, O'Grady J, Carithers RL et al. Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis: meta-analysis of individual patient data. Gut. 2011;60(2):255-260.

For more physician reviews of HM-related research, visit our website.

Clinical question: What is the effect of corticosteroid therapy on survival in severe alcoholic hepatitis?

Background: Previous meta-analyses have suggested a survival benefit of corticosteroid treatment restricted only to those patients with severe alcoholic hepatitis (AH), with little or no benefit in less severe disease. Other meta-analyses, however, have questioned the efficacy in AH regardless of disease severity.

Study design: Meta-analysis of individual patient data.

Setting: Five randomized controlled trials (RCT) enrolling 418 patients.

Synopsis: Individual patient data were obtained from five RCTs comparing corticosteroid treatment with placebo (n3), enteral nutrition (n1), or an antioxidant cocktail (n1). Researchers analyzed 221 patients allocated to corticosteroid treatment and 197 allocated to noncorticosteroid treatment. Twenty-eight-day survival was higher in corticosteroid treated patients than in noncorticosteroid-treated patients (79.97% vs. 65.76%, P=0.0005). A subgroup analysis was performed according to the Lille score. Patients were classified as complete responders, partial responders, and null responders. Corticosteroids had a significant effect on 28-day survival in complete responders and in partial responders, but not in null responders (91.16% vs. 79.46% vs. 53.36%, P<0.0001)

Bottom line: Corticosteroids significantly improve 28-day survival in patients with severe alcoholic hepatitis. The survival benefit is mainly observed in patients classified as responders by the Lille model.

Citation: Mathurin P, O'Grady J, Carithers RL et al. Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis: meta-analysis of individual patient data. Gut. 2011;60(2):255-260.

For more physician reviews of HM-related research, visit our website.

LONDON – The investigational agent blinatumomab could help more patients with relapsed or refractory acute lymphoblastic leukemia achieve remission, compared with conventional treatment strategies, interim findings of an exploratory phase II trial suggest.

Although a small study – just 12 patients were included in the analysis – "we saw a response rate of 75%," principal study investigator Dr. Max S. Topp said in an interview at the annual European Hematology Association congress.

"Obviously it’s a very small number of patients," Dr. Topp, a professor of medicine and consultant in hematology at the University of Wurzburg in Munich, conceded. "Nevertheless it’s basically more than double what you would expect."

The outlook for patients with relapsed or refractory B-precursor acute lymphoblastic leukemia (ALL) is often grim, Dr. Topp noted, with low response rates to intensive chemotherapy (17%-45%), and a high chance of further relapse with a median duration of 4-5 months for complete remission (CR).There is also a high rate of treatment-related mortality, with up to a quarter of patients dying during their treatment.

"Blinatumomab is a new kind of drug. It’s not actually an antibody in the classical sense, which is more passive. This is actually something that is actively looking for the tumor, as it uses the T cells to exert its action," Dr. Topp explained.

According to Micromet, the company developing the novel agent, blinatumomab is the most advanced of a new class of agents called BiTE (bispecific T-cell engager) antibodies. These agents are designed to direct cytotoxic T-cells to CD19-expressing cancer cells (Science 2008;321:974-7).

Data from a phase I study have already shown that blinatumomab is active in the treatment of relapsed or refractory B-cell non-Hodgkin’s lymphoma (American Society of Hematology annual meeting, abstract 2880). Dr. Topp and team have also demonstrated its tolerability and activity in patients with ALL who had minimal residual disease (MRD) (J. Clin. Oncol. 2011;29:2493-8).

"We then asked the question if you can actually treat full-blown relapse, and it looks like we can make a difference here," Dr. Topp observed.

The ongoing, open-label phase II study currently involves seven patients aged a median of 37 years who are being treated with blinatumomab at a dose of 15 mcg/m² per day over three cycles and for maintenance treatment. Another five patients, with a median age of 60 years, are receiving the drug at an initial dose of 5 mcg/m² per day, then at a dose of 15 or 30 mcg/m² per day (cohort 2). Blinatumomab is delivered via continuous intravenous infusion for 2 weeks, with a 2-week treatment-free period.

Although the agent is in its very early days, results show that it has great promise in the treatment of relapsed or refractory ALL. The overall CR rate was 75%, and 71% in patients given the steady 15-mcg dose of blinatumomab and 80% in those whose dose was increased in subsequent cycles.

The increasing dosing regimen appears to be associated with better tolerability. "Adapting the system to have a slow start with 5 mcg and going up to 15 mcg we have had no severe adverse events ... and that is great news," Dr. Topp observed.

Some of the most common side effects seen in the trial to date include raised gamma-glutamyltransferase and C-reactive protein, peripheral edema, fatigue, pyrexia. Blood fibrinogen and fibrin d-dimer have also been increased, suggesting that thrombotic complications could be a future concern.

The bottom line, said Dr. Topp, is that "we have a non-chemotherapy, immunotherapy-based, effective treatment for patients with relapsed ALL, with very good safety profile."

Research is ongoing and a further 10 patients are likely to be included in the current trial. "We’re looking at the safety issues. We have to find the most likely regimen which we would like to use," Dr. Topp said.

The study was funded by Micromet AG. Dr. Topp is the principal investigator for the trial and disclosed acting as a consultant to the company.

LONDON – The investigational agent blinatumomab could help more patients with relapsed or refractory acute lymphoblastic leukemia achieve remission, compared with conventional treatment strategies, interim findings of an exploratory phase II trial suggest.

Although a small study – just 12 patients were included in the analysis – "we saw a response rate of 75%," principal study investigator Dr. Max S. Topp said in an interview at the annual European Hematology Association congress.

"Obviously it’s a very small number of patients," Dr. Topp, a professor of medicine and consultant in hematology at the University of Wurzburg in Munich, conceded. "Nevertheless it’s basically more than double what you would expect."

The outlook for patients with relapsed or refractory B-precursor acute lymphoblastic leukemia (ALL) is often grim, Dr. Topp noted, with low response rates to intensive chemotherapy (17%-45%), and a high chance of further relapse with a median duration of 4-5 months for complete remission (CR).There is also a high rate of treatment-related mortality, with up to a quarter of patients dying during their treatment.

"Blinatumomab is a new kind of drug. It’s not actually an antibody in the classical sense, which is more passive. This is actually something that is actively looking for the tumor, as it uses the T cells to exert its action," Dr. Topp explained.

According to Micromet, the company developing the novel agent, blinatumomab is the most advanced of a new class of agents called BiTE (bispecific T-cell engager) antibodies. These agents are designed to direct cytotoxic T-cells to CD19-expressing cancer cells (Science 2008;321:974-7).

Data from a phase I study have already shown that blinatumomab is active in the treatment of relapsed or refractory B-cell non-Hodgkin’s lymphoma (American Society of Hematology annual meeting, abstract 2880). Dr. Topp and team have also demonstrated its tolerability and activity in patients with ALL who had minimal residual disease (MRD) (J. Clin. Oncol. 2011;29:2493-8).

"We then asked the question if you can actually treat full-blown relapse, and it looks like we can make a difference here," Dr. Topp observed.

The ongoing, open-label phase II study currently involves seven patients aged a median of 37 years who are being treated with blinatumomab at a dose of 15 mcg/m² per day over three cycles and for maintenance treatment. Another five patients, with a median age of 60 years, are receiving the drug at an initial dose of 5 mcg/m² per day, then at a dose of 15 or 30 mcg/m² per day (cohort 2). Blinatumomab is delivered via continuous intravenous infusion for 2 weeks, with a 2-week treatment-free period.

Although the agent is in its very early days, results show that it has great promise in the treatment of relapsed or refractory ALL. The overall CR rate was 75%, and 71% in patients given the steady 15-mcg dose of blinatumomab and 80% in those whose dose was increased in subsequent cycles.

The increasing dosing regimen appears to be associated with better tolerability. "Adapting the system to have a slow start with 5 mcg and going up to 15 mcg we have had no severe adverse events ... and that is great news," Dr. Topp observed.

Some of the most common side effects seen in the trial to date include raised gamma-glutamyltransferase and C-reactive protein, peripheral edema, fatigue, pyrexia. Blood fibrinogen and fibrin d-dimer have also been increased, suggesting that thrombotic complications could be a future concern.

The bottom line, said Dr. Topp, is that "we have a non-chemotherapy, immunotherapy-based, effective treatment for patients with relapsed ALL, with very good safety profile."

Research is ongoing and a further 10 patients are likely to be included in the current trial. "We’re looking at the safety issues. We have to find the most likely regimen which we would like to use," Dr. Topp said.

The study was funded by Micromet AG. Dr. Topp is the principal investigator for the trial and disclosed acting as a consultant to the company.

LONDON – The investigational agent blinatumomab could help more patients with relapsed or refractory acute lymphoblastic leukemia achieve remission, compared with conventional treatment strategies, interim findings of an exploratory phase II trial suggest.

Although a small study – just 12 patients were included in the analysis – "we saw a response rate of 75%," principal study investigator Dr. Max S. Topp said in an interview at the annual European Hematology Association congress.

"Obviously it’s a very small number of patients," Dr. Topp, a professor of medicine and consultant in hematology at the University of Wurzburg in Munich, conceded. "Nevertheless it’s basically more than double what you would expect."

The outlook for patients with relapsed or refractory B-precursor acute lymphoblastic leukemia (ALL) is often grim, Dr. Topp noted, with low response rates to intensive chemotherapy (17%-45%), and a high chance of further relapse with a median duration of 4-5 months for complete remission (CR).There is also a high rate of treatment-related mortality, with up to a quarter of patients dying during their treatment.

"Blinatumomab is a new kind of drug. It’s not actually an antibody in the classical sense, which is more passive. This is actually something that is actively looking for the tumor, as it uses the T cells to exert its action," Dr. Topp explained.

According to Micromet, the company developing the novel agent, blinatumomab is the most advanced of a new class of agents called BiTE (bispecific T-cell engager) antibodies. These agents are designed to direct cytotoxic T-cells to CD19-expressing cancer cells (Science 2008;321:974-7).

Data from a phase I study have already shown that blinatumomab is active in the treatment of relapsed or refractory B-cell non-Hodgkin’s lymphoma (American Society of Hematology annual meeting, abstract 2880). Dr. Topp and team have also demonstrated its tolerability and activity in patients with ALL who had minimal residual disease (MRD) (J. Clin. Oncol. 2011;29:2493-8).

"We then asked the question if you can actually treat full-blown relapse, and it looks like we can make a difference here," Dr. Topp observed.

The ongoing, open-label phase II study currently involves seven patients aged a median of 37 years who are being treated with blinatumomab at a dose of 15 mcg/m² per day over three cycles and for maintenance treatment. Another five patients, with a median age of 60 years, are receiving the drug at an initial dose of 5 mcg/m² per day, then at a dose of 15 or 30 mcg/m² per day (cohort 2). Blinatumomab is delivered via continuous intravenous infusion for 2 weeks, with a 2-week treatment-free period.

Although the agent is in its very early days, results show that it has great promise in the treatment of relapsed or refractory ALL. The overall CR rate was 75%, and 71% in patients given the steady 15-mcg dose of blinatumomab and 80% in those whose dose was increased in subsequent cycles.

The increasing dosing regimen appears to be associated with better tolerability. "Adapting the system to have a slow start with 5 mcg and going up to 15 mcg we have had no severe adverse events ... and that is great news," Dr. Topp observed.

Some of the most common side effects seen in the trial to date include raised gamma-glutamyltransferase and C-reactive protein, peripheral edema, fatigue, pyrexia. Blood fibrinogen and fibrin d-dimer have also been increased, suggesting that thrombotic complications could be a future concern.

The bottom line, said Dr. Topp, is that "we have a non-chemotherapy, immunotherapy-based, effective treatment for patients with relapsed ALL, with very good safety profile."

Research is ongoing and a further 10 patients are likely to be included in the current trial. "We’re looking at the safety issues. We have to find the most likely regimen which we would like to use," Dr. Topp said.

The study was funded by Micromet AG. Dr. Topp is the principal investigator for the trial and disclosed acting as a consultant to the company.

LOS ANGELES – For the first time, a pediatric stroke severity scale has been validated in a prospective clinical trial.

The study in 15 North American medical centers showed excellent interrater reliability when neurologists used a pediatric version of the National Institutes of Health Stroke Scale for adults to examine children aged 2-18 years with acute arterial ischemic stroke.

The neurologists used the Pediatric NIH Stroke Scale (PedNIHSS) on 113 patients who were examined daily from admission to discharge, or through day 7 of hospitalization.

Interrater reliability was tested in a subset of 25 patients who underwent simultaneous examinations by two pediatric neurologists.

Characteristics of the subgroup were similar to those of the entire cohort, Dr. Rebecca N. Ichord reported at the International Stroke Conference.

The simultaneous raters’ scores were identical in 60% of ratings and were within a 1-point difference in 84% of ratings (Stroke 2011;42:613-7).

Research into potential ways of preventing or treating childhood stroke has been stymied in the past by the lack of a validated and reliable pediatric stroke scale.

The PedNIHSS provides a way to index the severity of a child’s stroke, to make comparisons across treatment groups, and to get a baseline for predicting outcome, said Dr. Ichord, director of the pediatric stroke program at the Children’s Hospital of Philadelphia.

Clinicians, too, have been hungering for such a scale. "I have been asked over and over again [for a pediatric stroke scale] by clinicians who want to have a method of describing the severity of a child’s stroke," she said at the meeting, which was sponsored by the American Heart Association.

"It helps them with clinical decision making. It helps them to prepare parents and counsel parents. It helps to guide them as to how quickly and how urgently the child’s care should move forward. [Such a scale] is absolutely needed and wanted right now by clinicians on the front line," according to Dr. Ichord.

Characteristics of the patients and the strokes in the study were similar to those reported in previous pediatric stroke cohort studies, which suggests the current findings are generalizable and the PedNIHSS should be applicable in other settings.

Because all of the raters in the current study were pediatric neurologists or trainees, a separate study is needed to assess the PedNIHSS in the hands of other specialists, Dr. Ichord said.

The interrater reliability in the study compared favorably with that seen in studies of the adult NIHSS.

The pediatric version also found good interrater reliability for facial weakness, dysarthria, and ataxia, which was not seen with the adult stroke scale. The reasons for this difference are unclear.

The PedNIHSS was drafted by a consensus panel of pediatric and adult stroke experts. They limited the use of the pediatric scale to ages 2-18 years because younger children have limited language abilities, which are needed for use of the PedNIHSS.

Neonates and children younger than 2 years of age with acute ischemic stroke also frequently present without focal deficits, and so may require a scale with less emphasis on focal sensorimotor deficits, the investigators suggested.

A study is underway to compare PedNIHSS scores with infarct volume and with functional outcomes at 3 and 12 months.

Stroke affects 25 in 100,000 newborns and 12 in 100,000 children under 18 years of age. It is the sixth leading cause of death in children, according to the PedNIHSS Web site.

Ischemic stroke, in particular, is one of the top 10 causes of death among children, affecting 1.2-7.9 per 100,000 children aged 1 month to 18 years in North America and Europe, the investigators noted. Some 40%-60% of survivors are left with long-term motor and cognitive deficits that interfere with function.

Dr. Ichord and one of her associates in the study are on the clinical event committee for the Berlin Heart Trial for pediatric ventricular assist devices.

LOS ANGELES – For the first time, a pediatric stroke severity scale has been validated in a prospective clinical trial.

The study in 15 North American medical centers showed excellent interrater reliability when neurologists used a pediatric version of the National Institutes of Health Stroke Scale for adults to examine children aged 2-18 years with acute arterial ischemic stroke.

The neurologists used the Pediatric NIH Stroke Scale (PedNIHSS) on 113 patients who were examined daily from admission to discharge, or through day 7 of hospitalization.

Interrater reliability was tested in a subset of 25 patients who underwent simultaneous examinations by two pediatric neurologists.

Characteristics of the subgroup were similar to those of the entire cohort, Dr. Rebecca N. Ichord reported at the International Stroke Conference.

The simultaneous raters’ scores were identical in 60% of ratings and were within a 1-point difference in 84% of ratings (Stroke 2011;42:613-7).

Research into potential ways of preventing or treating childhood stroke has been stymied in the past by the lack of a validated and reliable pediatric stroke scale.

The PedNIHSS provides a way to index the severity of a child’s stroke, to make comparisons across treatment groups, and to get a baseline for predicting outcome, said Dr. Ichord, director of the pediatric stroke program at the Children’s Hospital of Philadelphia.

Clinicians, too, have been hungering for such a scale. "I have been asked over and over again [for a pediatric stroke scale] by clinicians who want to have a method of describing the severity of a child’s stroke," she said at the meeting, which was sponsored by the American Heart Association.

"It helps them with clinical decision making. It helps them to prepare parents and counsel parents. It helps to guide them as to how quickly and how urgently the child’s care should move forward. [Such a scale] is absolutely needed and wanted right now by clinicians on the front line," according to Dr. Ichord.

Characteristics of the patients and the strokes in the study were similar to those reported in previous pediatric stroke cohort studies, which suggests the current findings are generalizable and the PedNIHSS should be applicable in other settings.

Because all of the raters in the current study were pediatric neurologists or trainees, a separate study is needed to assess the PedNIHSS in the hands of other specialists, Dr. Ichord said.

The interrater reliability in the study compared favorably with that seen in studies of the adult NIHSS.

The pediatric version also found good interrater reliability for facial weakness, dysarthria, and ataxia, which was not seen with the adult stroke scale. The reasons for this difference are unclear.

The PedNIHSS was drafted by a consensus panel of pediatric and adult stroke experts. They limited the use of the pediatric scale to ages 2-18 years because younger children have limited language abilities, which are needed for use of the PedNIHSS.

Neonates and children younger than 2 years of age with acute ischemic stroke also frequently present without focal deficits, and so may require a scale with less emphasis on focal sensorimotor deficits, the investigators suggested.

A study is underway to compare PedNIHSS scores with infarct volume and with functional outcomes at 3 and 12 months.

Stroke affects 25 in 100,000 newborns and 12 in 100,000 children under 18 years of age. It is the sixth leading cause of death in children, according to the PedNIHSS Web site.

Ischemic stroke, in particular, is one of the top 10 causes of death among children, affecting 1.2-7.9 per 100,000 children aged 1 month to 18 years in North America and Europe, the investigators noted. Some 40%-60% of survivors are left with long-term motor and cognitive deficits that interfere with function.

Dr. Ichord and one of her associates in the study are on the clinical event committee for the Berlin Heart Trial for pediatric ventricular assist devices.

LOS ANGELES – For the first time, a pediatric stroke severity scale has been validated in a prospective clinical trial.

The study in 15 North American medical centers showed excellent interrater reliability when neurologists used a pediatric version of the National Institutes of Health Stroke Scale for adults to examine children aged 2-18 years with acute arterial ischemic stroke.

The neurologists used the Pediatric NIH Stroke Scale (PedNIHSS) on 113 patients who were examined daily from admission to discharge, or through day 7 of hospitalization.

Interrater reliability was tested in a subset of 25 patients who underwent simultaneous examinations by two pediatric neurologists.

Characteristics of the subgroup were similar to those of the entire cohort, Dr. Rebecca N. Ichord reported at the International Stroke Conference.

The simultaneous raters’ scores were identical in 60% of ratings and were within a 1-point difference in 84% of ratings (Stroke 2011;42:613-7).

Research into potential ways of preventing or treating childhood stroke has been stymied in the past by the lack of a validated and reliable pediatric stroke scale.

The PedNIHSS provides a way to index the severity of a child’s stroke, to make comparisons across treatment groups, and to get a baseline for predicting outcome, said Dr. Ichord, director of the pediatric stroke program at the Children’s Hospital of Philadelphia.

Clinicians, too, have been hungering for such a scale. "I have been asked over and over again [for a pediatric stroke scale] by clinicians who want to have a method of describing the severity of a child’s stroke," she said at the meeting, which was sponsored by the American Heart Association.

"It helps them with clinical decision making. It helps them to prepare parents and counsel parents. It helps to guide them as to how quickly and how urgently the child’s care should move forward. [Such a scale] is absolutely needed and wanted right now by clinicians on the front line," according to Dr. Ichord.

Characteristics of the patients and the strokes in the study were similar to those reported in previous pediatric stroke cohort studies, which suggests the current findings are generalizable and the PedNIHSS should be applicable in other settings.

Because all of the raters in the current study were pediatric neurologists or trainees, a separate study is needed to assess the PedNIHSS in the hands of other specialists, Dr. Ichord said.

The interrater reliability in the study compared favorably with that seen in studies of the adult NIHSS.

The pediatric version also found good interrater reliability for facial weakness, dysarthria, and ataxia, which was not seen with the adult stroke scale. The reasons for this difference are unclear.

The PedNIHSS was drafted by a consensus panel of pediatric and adult stroke experts. They limited the use of the pediatric scale to ages 2-18 years because younger children have limited language abilities, which are needed for use of the PedNIHSS.

Neonates and children younger than 2 years of age with acute ischemic stroke also frequently present without focal deficits, and so may require a scale with less emphasis on focal sensorimotor deficits, the investigators suggested.

A study is underway to compare PedNIHSS scores with infarct volume and with functional outcomes at 3 and 12 months.

Stroke affects 25 in 100,000 newborns and 12 in 100,000 children under 18 years of age. It is the sixth leading cause of death in children, according to the PedNIHSS Web site.

Ischemic stroke, in particular, is one of the top 10 causes of death among children, affecting 1.2-7.9 per 100,000 children aged 1 month to 18 years in North America and Europe, the investigators noted. Some 40%-60% of survivors are left with long-term motor and cognitive deficits that interfere with function.

Dr. Ichord and one of her associates in the study are on the clinical event committee for the Berlin Heart Trial for pediatric ventricular assist devices.

CHICAGO – Vascular surgery trainees are increasingly turning to online texts for clinical information and seek more training on the business aspects of vascular surgery and noninvasive laboratory studies, according to a survey by the Association of Program Directors in Vascular Surgery.

The survey included 163 respondents, of which 46 were in an integrated (0-5) residency program and 117 were currently in or new graduates of an independent (5+2) program.

When asked how they obtained clinical information on the wards or prior to an operation, integrated program respondents said online text books were their go-to source, while independent responders preferred a traditional textbook. Asking a colleague came in second for both groups.

"You can certainly figure out why that might be," said Dr. Michael Dalsing who reported the findings at the annual meeting of the Peripheral Vascular Surgical Society. "If you’re a PGY 1 - 3, patient care is your primary concern. While for those with additional levels of training, specific vascular concerns and surgery are most important."

One-on-one instruction was the best way both groups of trainees reported learning new information. Integrated residents were less enthusiastic than independent residents about small group discussions, while simulation training ranked higher among integrated residents.

When asked to grade their overall program, both programs ranked their endovascular training as excellent.

"Less than a decade you would not have seen endovascular training as the best part of their program, and now nearly 70% said it’s excellent," said Dr. Dalsing, of Indiana University.

Other "excellent" ratings included involvement of teaching faculty, open abdominal and aortic/mesenteric/renal training, didactic teaching and responsiveness to resident stresses. Appropriate performance feedback and support in their job search received "good" marks.

When asked if training in a specific area was appropriate, the business aspects of vascular surgery were judged the most underserved among both integrated and independent (69% vs. 70%) trainees, followed by coding and billing (66% and 64%). The next closest area in need of more attention was formal clinical research training, with just 27% and 35% of trainees, respectively, expressing this opinion. Surgical training and vascular lab/venous training were judged "just right" by more than 75% of respondents.

The ability to actually perform noninvasive vascular laboratory studies requires more attention, with a whopping 49% of integrated program trainees and 59% of independent program trainees viewing training in this area as "fair or nonexistent." Training in vascular laboratory interpretation received the same marks by 29% and 34% of trainees, respectively. About 85% of all trainees, however, view noninvasive vascular lab training as essential in future practice.

Dr. Joseph Mills, of the University of Arizona, rose from the audience to express alarm at these findings and asked what is being done to standardize the curriculum in the vascular lab. Dr. Dalsing said that CDs are available to educators to standardize training, but added that educators will have to become more aggressive in quantifying that the educational experience at their institution has met expected standards.

The two groups of trainees were split over the 80-hour work week. Independent trainees were significantly more likely than integrated trainees to view the 80-hour work week as detrimental to the continuity of care (62% vs. 24%, P value = .0001), while integrated trainees were significantly more likely to view the rule as essential to avoid fatigue and errors (82% vs. 42%, P = .0001).

CHICAGO – Vascular surgery trainees are increasingly turning to online texts for clinical information and seek more training on the business aspects of vascular surgery and noninvasive laboratory studies, according to a survey by the Association of Program Directors in Vascular Surgery.

The survey included 163 respondents, of which 46 were in an integrated (0-5) residency program and 117 were currently in or new graduates of an independent (5+2) program.

When asked how they obtained clinical information on the wards or prior to an operation, integrated program respondents said online text books were their go-to source, while independent responders preferred a traditional textbook. Asking a colleague came in second for both groups.

"You can certainly figure out why that might be," said Dr. Michael Dalsing who reported the findings at the annual meeting of the Peripheral Vascular Surgical Society. "If you’re a PGY 1 - 3, patient care is your primary concern. While for those with additional levels of training, specific vascular concerns and surgery are most important."

One-on-one instruction was the best way both groups of trainees reported learning new information. Integrated residents were less enthusiastic than independent residents about small group discussions, while simulation training ranked higher among integrated residents.

When asked to grade their overall program, both programs ranked their endovascular training as excellent.

"Less than a decade you would not have seen endovascular training as the best part of their program, and now nearly 70% said it’s excellent," said Dr. Dalsing, of Indiana University.

Other "excellent" ratings included involvement of teaching faculty, open abdominal and aortic/mesenteric/renal training, didactic teaching and responsiveness to resident stresses. Appropriate performance feedback and support in their job search received "good" marks.

When asked if training in a specific area was appropriate, the business aspects of vascular surgery were judged the most underserved among both integrated and independent (69% vs. 70%) trainees, followed by coding and billing (66% and 64%). The next closest area in need of more attention was formal clinical research training, with just 27% and 35% of trainees, respectively, expressing this opinion. Surgical training and vascular lab/venous training were judged "just right" by more than 75% of respondents.

The ability to actually perform noninvasive vascular laboratory studies requires more attention, with a whopping 49% of integrated program trainees and 59% of independent program trainees viewing training in this area as "fair or nonexistent." Training in vascular laboratory interpretation received the same marks by 29% and 34% of trainees, respectively. About 85% of all trainees, however, view noninvasive vascular lab training as essential in future practice.

Dr. Joseph Mills, of the University of Arizona, rose from the audience to express alarm at these findings and asked what is being done to standardize the curriculum in the vascular lab. Dr. Dalsing said that CDs are available to educators to standardize training, but added that educators will have to become more aggressive in quantifying that the educational experience at their institution has met expected standards.

The two groups of trainees were split over the 80-hour work week. Independent trainees were significantly more likely than integrated trainees to view the 80-hour work week as detrimental to the continuity of care (62% vs. 24%, P value = .0001), while integrated trainees were significantly more likely to view the rule as essential to avoid fatigue and errors (82% vs. 42%, P = .0001).

CHICAGO – Vascular surgery trainees are increasingly turning to online texts for clinical information and seek more training on the business aspects of vascular surgery and noninvasive laboratory studies, according to a survey by the Association of Program Directors in Vascular Surgery.

The survey included 163 respondents, of which 46 were in an integrated (0-5) residency program and 117 were currently in or new graduates of an independent (5+2) program.

When asked how they obtained clinical information on the wards or prior to an operation, integrated program respondents said online text books were their go-to source, while independent responders preferred a traditional textbook. Asking a colleague came in second for both groups.

"You can certainly figure out why that might be," said Dr. Michael Dalsing who reported the findings at the annual meeting of the Peripheral Vascular Surgical Society. "If you’re a PGY 1 - 3, patient care is your primary concern. While for those with additional levels of training, specific vascular concerns and surgery are most important."

One-on-one instruction was the best way both groups of trainees reported learning new information. Integrated residents were less enthusiastic than independent residents about small group discussions, while simulation training ranked higher among integrated residents.

When asked to grade their overall program, both programs ranked their endovascular training as excellent.

"Less than a decade you would not have seen endovascular training as the best part of their program, and now nearly 70% said it’s excellent," said Dr. Dalsing, of Indiana University.

Other "excellent" ratings included involvement of teaching faculty, open abdominal and aortic/mesenteric/renal training, didactic teaching and responsiveness to resident stresses. Appropriate performance feedback and support in their job search received "good" marks.

When asked if training in a specific area was appropriate, the business aspects of vascular surgery were judged the most underserved among both integrated and independent (69% vs. 70%) trainees, followed by coding and billing (66% and 64%). The next closest area in need of more attention was formal clinical research training, with just 27% and 35% of trainees, respectively, expressing this opinion. Surgical training and vascular lab/venous training were judged "just right" by more than 75% of respondents.

The ability to actually perform noninvasive vascular laboratory studies requires more attention, with a whopping 49% of integrated program trainees and 59% of independent program trainees viewing training in this area as "fair or nonexistent." Training in vascular laboratory interpretation received the same marks by 29% and 34% of trainees, respectively. About 85% of all trainees, however, view noninvasive vascular lab training as essential in future practice.

Dr. Joseph Mills, of the University of Arizona, rose from the audience to express alarm at these findings and asked what is being done to standardize the curriculum in the vascular lab. Dr. Dalsing said that CDs are available to educators to standardize training, but added that educators will have to become more aggressive in quantifying that the educational experience at their institution has met expected standards.

The two groups of trainees were split over the 80-hour work week. Independent trainees were significantly more likely than integrated trainees to view the 80-hour work week as detrimental to the continuity of care (62% vs. 24%, P value = .0001), while integrated trainees were significantly more likely to view the rule as essential to avoid fatigue and errors (82% vs. 42%, P = .0001).

Hospitalists might be able to save their institutions time and money by shuttling out patients who have a low risk for acute pulmonary embolism (PE), according to one researcher.

Donald Yealy, MD, chair of the Department of Emergency Medicine at the University of Pittsburgh School of Medicine, was among the authors of a new study that reported that in certain cases, "outpatient care can safely and effectively be used in place of inpatient care" (Lancet. 2011;378(9785):41-48).

Dr. Yealy says HM should pay close attention to the results, as patients moved to the outpatient setting clear bed space for more acute cases. "[Hospitalists] should identify low-risk patients and try as quickly as possible to return patients to the setting they prefer: their home," he says.

In a primary analysis, the international noninferiority trial reported that one of 171 outpatients (0.006%) developed recurrent VTE within 90 days compared with none of 168 inpatients (95% upper confidence limit [UCL] 2.7%; P=0.011). Mean length of stay was 0.5 days for outpatients, compared with 3.9 days.

Dr. Yealy notes that the next step for research is to determine which treatment to use for PE cases, as his study focused just on where the treatment was rendered. He also notes that the review focused only on patients diagnosed by ED physicians as having a PE severity index risk class 1 or 2. He compares potential future treatment therapies to those for cancer patients, for which "not everyone who has cancer has a high risk for terrible outcomes."

"All pulmonary emboli are not the same," Dr. Yealy adds. "If you use a strategy that identifies the lowest-risk patients, you have a lot of options. … We need to right-size our approach."

Hospitalists might be able to save their institutions time and money by shuttling out patients who have a low risk for acute pulmonary embolism (PE), according to one researcher.

Donald Yealy, MD, chair of the Department of Emergency Medicine at the University of Pittsburgh School of Medicine, was among the authors of a new study that reported that in certain cases, "outpatient care can safely and effectively be used in place of inpatient care" (Lancet. 2011;378(9785):41-48).

Dr. Yealy says HM should pay close attention to the results, as patients moved to the outpatient setting clear bed space for more acute cases. "[Hospitalists] should identify low-risk patients and try as quickly as possible to return patients to the setting they prefer: their home," he says.

In a primary analysis, the international noninferiority trial reported that one of 171 outpatients (0.006%) developed recurrent VTE within 90 days compared with none of 168 inpatients (95% upper confidence limit [UCL] 2.7%; P=0.011). Mean length of stay was 0.5 days for outpatients, compared with 3.9 days.

Dr. Yealy notes that the next step for research is to determine which treatment to use for PE cases, as his study focused just on where the treatment was rendered. He also notes that the review focused only on patients diagnosed by ED physicians as having a PE severity index risk class 1 or 2. He compares potential future treatment therapies to those for cancer patients, for which "not everyone who has cancer has a high risk for terrible outcomes."

"All pulmonary emboli are not the same," Dr. Yealy adds. "If you use a strategy that identifies the lowest-risk patients, you have a lot of options. … We need to right-size our approach."

Hospitalists might be able to save their institutions time and money by shuttling out patients who have a low risk for acute pulmonary embolism (PE), according to one researcher.

Donald Yealy, MD, chair of the Department of Emergency Medicine at the University of Pittsburgh School of Medicine, was among the authors of a new study that reported that in certain cases, "outpatient care can safely and effectively be used in place of inpatient care" (Lancet. 2011;378(9785):41-48).

Dr. Yealy says HM should pay close attention to the results, as patients moved to the outpatient setting clear bed space for more acute cases. "[Hospitalists] should identify low-risk patients and try as quickly as possible to return patients to the setting they prefer: their home," he says.

In a primary analysis, the international noninferiority trial reported that one of 171 outpatients (0.006%) developed recurrent VTE within 90 days compared with none of 168 inpatients (95% upper confidence limit [UCL] 2.7%; P=0.011). Mean length of stay was 0.5 days for outpatients, compared with 3.9 days.

Dr. Yealy notes that the next step for research is to determine which treatment to use for PE cases, as his study focused just on where the treatment was rendered. He also notes that the review focused only on patients diagnosed by ED physicians as having a PE severity index risk class 1 or 2. He compares potential future treatment therapies to those for cancer patients, for which "not everyone who has cancer has a high risk for terrible outcomes."

"All pulmonary emboli are not the same," Dr. Yealy adds. "If you use a strategy that identifies the lowest-risk patients, you have a lot of options. … We need to right-size our approach."

As part of its new hospital ratings, Consumer Reports has reported that some well-established teaching hospitals have higher rates of central-line-catheter-related bloodstream infections (CRBSIs) than the national average. Three Council of Teaching Hospitals members received the magazine's lowest rating, and 64 received its second-lowest rating for infection prevention.

The Association of Professionals in Infection Control and Epidemiology has challenged the findings as only a partial picture of a complex problem.

"We understand that the data are aggregated, but there are issues with the aggregation," says Carolyn Chrisman, BBA, vice president for quality integration and improvement at Carilion Clinic, whose Roanoke, Va.-based Carilion Medical Center was one of Consumer Reports' second-lowest-rated teaching hospitals, with a rate that it reported was 24% worse than national rates for its mix of ICUs in calendar year 2010. "One of the biggest issues is that the type of patients seen in Level One trauma centers such as ours is very different. We work hard to follow the guidelines, but some of these patients are just more compromised."

Checklists for preventing CRBSIs are widely used in U.S. hospitals and have been shown to reduce infection rates. "But that's only part of the story. What about care and maintenance of the central line after it is inserted, which we're trying to focus on here?" Chrisman says.

At Carilion, a quality team was chartered in 2007 to address BSIs, and that group is planning to reconvene. Having the right supplies readily available when needed for central-line insertions is another challenge, and Carilion has developed carts and kits to help make sure that they are, Chrisman adds. "We also have data from 2011 that show significant improvement" over the 2010 data reported by Consumer Reports, she says.

Bradley Flansbaum, DO, MPH, FACP, director of the hospitalist program at Lenox Hill Hospital in New York City, another teaching hospital on Consumer Reports' lower-performing list for BSIs, with a rate that was 75% worse than national rates for the hospital's mix of ICUs, notes the benchmark has been set high for hospitals. “Some institutions have shown zero bloodstream infections, so the question of what's acceptable has been established. We know what we need to do," he says.

But achieving zero infections is more than just following the checklists, he adds. Ultimately it requires a change of hospital culture, even around issues as mundane as poor hand hygiene, against which all hospitals struggle, he says.

For more information on preventing BSIs, visit the Institute for Healthcare Improvement's Five Million Lives Campaign.

As part of its new hospital ratings, Consumer Reports has reported that some well-established teaching hospitals have higher rates of central-line-catheter-related bloodstream infections (CRBSIs) than the national average. Three Council of Teaching Hospitals members received the magazine's lowest rating, and 64 received its second-lowest rating for infection prevention.

The Association of Professionals in Infection Control and Epidemiology has challenged the findings as only a partial picture of a complex problem.

"We understand that the data are aggregated, but there are issues with the aggregation," says Carolyn Chrisman, BBA, vice president for quality integration and improvement at Carilion Clinic, whose Roanoke, Va.-based Carilion Medical Center was one of Consumer Reports' second-lowest-rated teaching hospitals, with a rate that it reported was 24% worse than national rates for its mix of ICUs in calendar year 2010. "One of the biggest issues is that the type of patients seen in Level One trauma centers such as ours is very different. We work hard to follow the guidelines, but some of these patients are just more compromised."

Checklists for preventing CRBSIs are widely used in U.S. hospitals and have been shown to reduce infection rates. "But that's only part of the story. What about care and maintenance of the central line after it is inserted, which we're trying to focus on here?" Chrisman says.

At Carilion, a quality team was chartered in 2007 to address BSIs, and that group is planning to reconvene. Having the right supplies readily available when needed for central-line insertions is another challenge, and Carilion has developed carts and kits to help make sure that they are, Chrisman adds. "We also have data from 2011 that show significant improvement" over the 2010 data reported by Consumer Reports, she says.

Bradley Flansbaum, DO, MPH, FACP, director of the hospitalist program at Lenox Hill Hospital in New York City, another teaching hospital on Consumer Reports' lower-performing list for BSIs, with a rate that was 75% worse than national rates for the hospital's mix of ICUs, notes the benchmark has been set high for hospitals. “Some institutions have shown zero bloodstream infections, so the question of what's acceptable has been established. We know what we need to do," he says.

But achieving zero infections is more than just following the checklists, he adds. Ultimately it requires a change of hospital culture, even around issues as mundane as poor hand hygiene, against which all hospitals struggle, he says.

For more information on preventing BSIs, visit the Institute for Healthcare Improvement's Five Million Lives Campaign.

As part of its new hospital ratings, Consumer Reports has reported that some well-established teaching hospitals have higher rates of central-line-catheter-related bloodstream infections (CRBSIs) than the national average. Three Council of Teaching Hospitals members received the magazine's lowest rating, and 64 received its second-lowest rating for infection prevention.

The Association of Professionals in Infection Control and Epidemiology has challenged the findings as only a partial picture of a complex problem.

"We understand that the data are aggregated, but there are issues with the aggregation," says Carolyn Chrisman, BBA, vice president for quality integration and improvement at Carilion Clinic, whose Roanoke, Va.-based Carilion Medical Center was one of Consumer Reports' second-lowest-rated teaching hospitals, with a rate that it reported was 24% worse than national rates for its mix of ICUs in calendar year 2010. "One of the biggest issues is that the type of patients seen in Level One trauma centers such as ours is very different. We work hard to follow the guidelines, but some of these patients are just more compromised."

Checklists for preventing CRBSIs are widely used in U.S. hospitals and have been shown to reduce infection rates. "But that's only part of the story. What about care and maintenance of the central line after it is inserted, which we're trying to focus on here?" Chrisman says.

At Carilion, a quality team was chartered in 2007 to address BSIs, and that group is planning to reconvene. Having the right supplies readily available when needed for central-line insertions is another challenge, and Carilion has developed carts and kits to help make sure that they are, Chrisman adds. "We also have data from 2011 that show significant improvement" over the 2010 data reported by Consumer Reports, she says.

Bradley Flansbaum, DO, MPH, FACP, director of the hospitalist program at Lenox Hill Hospital in New York City, another teaching hospital on Consumer Reports' lower-performing list for BSIs, with a rate that was 75% worse than national rates for the hospital's mix of ICUs, notes the benchmark has been set high for hospitals. “Some institutions have shown zero bloodstream infections, so the question of what's acceptable has been established. We know what we need to do," he says.

But achieving zero infections is more than just following the checklists, he adds. Ultimately it requires a change of hospital culture, even around issues as mundane as poor hand hygiene, against which all hospitals struggle, he says.

For more information on preventing BSIs, visit the Institute for Healthcare Improvement's Five Million Lives Campaign.