Congressional action has delayed a potentially devastating cut in Medicare physician reimbursements for at least two more months, while a separate attempt to delay the looming elimination of Medicare’s consultation billing codes now seems increasingly unlikely to succeed.

In November, the House of Representatives passed a bill that would have rescinded the 21.2% cut to Medicare’s physician fee schedule for 2010 (dictated by the current formula’s sustainable growth rate, or SGR). But the Senate balked at the expected $247 billion price tag, and was unable to muster enough votes to avert a filibuster.

Trying a different tack, House Democrats used the must-pass Defense appropriations bill to push through an amendment freezing Medicare payments at current levels through February, buying Congress more time to find a better solution. The Senate followed suit by approving the bill on Saturday, though a longer-term fix is still in flux. A joint letter by SHM, the American Medical Association (AMA), and other physicians groups calls for a permanent end to the SGR formula—a potentially contentious issue that will await Congress in 2010.

Meanwhile, a request from the AMA and other physician groups to delay the elimination of Medicare consultation codes for a year to allow more time for guidance and ironing out technical issues has yielded no guarantees from the Centers for Medicare and Medicaid Services (CMS). Sen. Arlen Specter (D-Penn.) had offered an amendment seeking such a delay to the Senate’s healthcare reform legislation, but a spokesperson from Spector's office said the amendment did not move forward with the Senate bill—an exclusion that now makes a last-minute reprieve unlikely.

In the interim, CMS has released a 29-page transmittal explaining how the eliminated codes will be replaced by existing evaluation and management codes. Click here to download a PDF of the transmittal.

Congressional action has delayed a potentially devastating cut in Medicare physician reimbursements for at least two more months, while a separate attempt to delay the looming elimination of Medicare’s consultation billing codes now seems increasingly unlikely to succeed.

In November, the House of Representatives passed a bill that would have rescinded the 21.2% cut to Medicare’s physician fee schedule for 2010 (dictated by the current formula’s sustainable growth rate, or SGR). But the Senate balked at the expected $247 billion price tag, and was unable to muster enough votes to avert a filibuster.

Trying a different tack, House Democrats used the must-pass Defense appropriations bill to push through an amendment freezing Medicare payments at current levels through February, buying Congress more time to find a better solution. The Senate followed suit by approving the bill on Saturday, though a longer-term fix is still in flux. A joint letter by SHM, the American Medical Association (AMA), and other physicians groups calls for a permanent end to the SGR formula—a potentially contentious issue that will await Congress in 2010.

Meanwhile, a request from the AMA and other physician groups to delay the elimination of Medicare consultation codes for a year to allow more time for guidance and ironing out technical issues has yielded no guarantees from the Centers for Medicare and Medicaid Services (CMS). Sen. Arlen Specter (D-Penn.) had offered an amendment seeking such a delay to the Senate’s healthcare reform legislation, but a spokesperson from Spector's office said the amendment did not move forward with the Senate bill—an exclusion that now makes a last-minute reprieve unlikely.

In the interim, CMS has released a 29-page transmittal explaining how the eliminated codes will be replaced by existing evaluation and management codes. Click here to download a PDF of the transmittal.

Congressional action has delayed a potentially devastating cut in Medicare physician reimbursements for at least two more months, while a separate attempt to delay the looming elimination of Medicare’s consultation billing codes now seems increasingly unlikely to succeed.

In November, the House of Representatives passed a bill that would have rescinded the 21.2% cut to Medicare’s physician fee schedule for 2010 (dictated by the current formula’s sustainable growth rate, or SGR). But the Senate balked at the expected $247 billion price tag, and was unable to muster enough votes to avert a filibuster.

Trying a different tack, House Democrats used the must-pass Defense appropriations bill to push through an amendment freezing Medicare payments at current levels through February, buying Congress more time to find a better solution. The Senate followed suit by approving the bill on Saturday, though a longer-term fix is still in flux. A joint letter by SHM, the American Medical Association (AMA), and other physicians groups calls for a permanent end to the SGR formula—a potentially contentious issue that will await Congress in 2010.

Meanwhile, a request from the AMA and other physician groups to delay the elimination of Medicare consultation codes for a year to allow more time for guidance and ironing out technical issues has yielded no guarantees from the Centers for Medicare and Medicaid Services (CMS). Sen. Arlen Specter (D-Penn.) had offered an amendment seeking such a delay to the Senate’s healthcare reform legislation, but a spokesperson from Spector's office said the amendment did not move forward with the Senate bill—an exclusion that now makes a last-minute reprieve unlikely.

In the interim, CMS has released a 29-page transmittal explaining how the eliminated codes will be replaced by existing evaluation and management codes. Click here to download a PDF of the transmittal.

Project BOOST (Better Outcomes for Older Adults through Safer Transitions) is getting, well, a pretty big boost in 2010.

The pilot transitional-care program implemented at 30 sites in the past 18 months pairs SHM mentors with hospitalists to improve care via a discharge planning toolkit. Preliminary plans call for up to 45 additional sites staggered over three cohorts in the next 12 months.

Tina Budnitz, MPH, SHM senior advisor and director of Project BOOST, says the initiative also is working to create a tuition-based model, planning an educational Web-based seminar and standardized “teachback” materials. The BOOST team also is promoting an Internet listserv that hospitalists at the debut sites have used as a communal communication tool.

“It is a big jump,” Budnitz acknowledges. “We think the secret sauce that’s made it work so far will be able to scale.”

Quantifiable data from the first six sites, which were selected for the program in the summer of 2008, could be released this spring. A lack of metrics, however, has done little to stymie the initiative’s growth. Two sites—Hospital of the University of Pennsylvania in Philadelphia and St. Mary’s Health Center in St. Louis, Mo.—already have won safety awards related to the program.

One of the program’s mentors says the early success can be tied to hospitalists’ commitment to using the toolkit as the basis of a transitional-care upgrade, instead of expecting the program’s presence alone to improve care.

“It’s way more than what is BOOST and ‘how are we going to implement?’ ” says Janet Nagamine, MD, FHM, hospitalist at Kaiser Permanente in Santa Clara, Calif., SHM board member, and chair of SHM’s Hospital Quality and Patient Safety Committee. “They have really looked at their entire discharge process and done a lot of looking at their individual and specific challenges and how to overcome them.”

Project BOOST (Better Outcomes for Older Adults through Safer Transitions) is getting, well, a pretty big boost in 2010.

The pilot transitional-care program implemented at 30 sites in the past 18 months pairs SHM mentors with hospitalists to improve care via a discharge planning toolkit. Preliminary plans call for up to 45 additional sites staggered over three cohorts in the next 12 months.

Tina Budnitz, MPH, SHM senior advisor and director of Project BOOST, says the initiative also is working to create a tuition-based model, planning an educational Web-based seminar and standardized “teachback” materials. The BOOST team also is promoting an Internet listserv that hospitalists at the debut sites have used as a communal communication tool.

“It is a big jump,” Budnitz acknowledges. “We think the secret sauce that’s made it work so far will be able to scale.”

Quantifiable data from the first six sites, which were selected for the program in the summer of 2008, could be released this spring. A lack of metrics, however, has done little to stymie the initiative’s growth. Two sites—Hospital of the University of Pennsylvania in Philadelphia and St. Mary’s Health Center in St. Louis, Mo.—already have won safety awards related to the program.

One of the program’s mentors says the early success can be tied to hospitalists’ commitment to using the toolkit as the basis of a transitional-care upgrade, instead of expecting the program’s presence alone to improve care.

“It’s way more than what is BOOST and ‘how are we going to implement?’ ” says Janet Nagamine, MD, FHM, hospitalist at Kaiser Permanente in Santa Clara, Calif., SHM board member, and chair of SHM’s Hospital Quality and Patient Safety Committee. “They have really looked at their entire discharge process and done a lot of looking at their individual and specific challenges and how to overcome them.”

Project BOOST (Better Outcomes for Older Adults through Safer Transitions) is getting, well, a pretty big boost in 2010.

The pilot transitional-care program implemented at 30 sites in the past 18 months pairs SHM mentors with hospitalists to improve care via a discharge planning toolkit. Preliminary plans call for up to 45 additional sites staggered over three cohorts in the next 12 months.

Tina Budnitz, MPH, SHM senior advisor and director of Project BOOST, says the initiative also is working to create a tuition-based model, planning an educational Web-based seminar and standardized “teachback” materials. The BOOST team also is promoting an Internet listserv that hospitalists at the debut sites have used as a communal communication tool.

“It is a big jump,” Budnitz acknowledges. “We think the secret sauce that’s made it work so far will be able to scale.”

Quantifiable data from the first six sites, which were selected for the program in the summer of 2008, could be released this spring. A lack of metrics, however, has done little to stymie the initiative’s growth. Two sites—Hospital of the University of Pennsylvania in Philadelphia and St. Mary’s Health Center in St. Louis, Mo.—already have won safety awards related to the program.

One of the program’s mentors says the early success can be tied to hospitalists’ commitment to using the toolkit as the basis of a transitional-care upgrade, instead of expecting the program’s presence alone to improve care.

“It’s way more than what is BOOST and ‘how are we going to implement?’ ” says Janet Nagamine, MD, FHM, hospitalist at Kaiser Permanente in Santa Clara, Calif., SHM board member, and chair of SHM’s Hospital Quality and Patient Safety Committee. “They have really looked at their entire discharge process and done a lot of looking at their individual and specific challenges and how to overcome them.”

There's a new old drug for chronic myeloid leukemia, and it seems to work in patients who don't respond to any of the approved therapies for this disease. Dr. Jorge Cortes discusses the potential of omacetaxine mepesuccinate at the annual meeting of the American Society of Hematology.

There's a new old drug for chronic myeloid leukemia, and it seems to work in patients who don't respond to any of the approved therapies for this disease. Dr. Jorge Cortes discusses the potential of omacetaxine mepesuccinate at the annual meeting of the American Society of Hematology.

There's a new old drug for chronic myeloid leukemia, and it seems to work in patients who don't respond to any of the approved therapies for this disease. Dr. Jorge Cortes discusses the potential of omacetaxine mepesuccinate at the annual meeting of the American Society of Hematology.

In the VISTA trial, the Spanish Myeloma Group created an induction regimen of bortezomib, melphalan, and prednisone that elderly patients could tolerate. This year the group took that regimen a step further.

In the VISTA trial, the Spanish Myeloma Group created an induction regimen of bortezomib, melphalan, and prednisone that elderly patients could tolerate. This year the group took that regimen a step further.

In the VISTA trial, the Spanish Myeloma Group created an induction regimen of bortezomib, melphalan, and prednisone that elderly patients could tolerate. This year the group took that regimen a step further.

Bendamustine plus rituximab has the potential to replace standard CHOP chemotherapy plus rituximab in the first-line treatment of advanced lymphomas. Dr. Mathias J. Rummel discusses data presented at the annual meeting of the American Society of Hematology.

Bendamustine plus rituximab has the potential to replace standard CHOP chemotherapy plus rituximab in the first-line treatment of advanced lymphomas. Dr. Mathias J. Rummel discusses data presented at the annual meeting of the American Society of Hematology.

Bendamustine plus rituximab has the potential to replace standard CHOP chemotherapy plus rituximab in the first-line treatment of advanced lymphomas. Dr. Mathias J. Rummel discusses data presented at the annual meeting of the American Society of Hematology.

Many of the medical journals read most by hospitalists, including the New England Journal of Medicine and the Journal of the American Medical Association, are adopting a new set of guidelines for the disclosure of potential conflicts of interest, a move the journals and researchers say is a step toward further transparency of authors' competing loyalties.

"From the perspective of an investigator and an end-user of the scientific literature, this is a positive development," says Andrew Masica, MD, MSCI, FHM, director of clinical effectiveness at Baylor Health Care System in Waco, Texas. "In many cases, a work's biggest impact is at the time of its initial release. It is important to provide full information on potential conflicts of interest at this early stage, rather than having something disclosed further down the road."

The new reporting guidelines were introduced in the fall by the International Committee of Medical Journal Editors and are being phased in at member journals. Authors will be asked to disclose four types of information, according to an NEJM editorial:¹

• Financial associations tied to the study they worked on; 
  

   

• Financial ties that could have an "interest in the general area of the submitted manuscript;" 
  

   

• Similar financial associations involving spouses and children under 18 years of age; and
  

   

• Relevant nonfinancial associations.

 

The new rules "align well with the overall trend towards transparency in healthcare," says Dr. Masica, who published this year in the Journal of Hospital Medicine. "Safety and quality data at both the hospital and practitioner level are increasingly available to the public; consistency with disclosure helps move research toward that same standard."

To that end, JHM is updating its peer-review submission Web site to incorporate the new changes and expects to make an announcement on its progress in April. "Transparency is good for healthcare delivery and establishing trust with our primary focus—the care of hospitalized patients," says Mark V. Williams, MD, FACP, FHM, JHM editor-in-chief.

Download the new ICMJE disclosure form and view completed samples.

Reference

1. Glickman SW, McHutchison JG, Peterson ED, et al. Ethical and scientific implications of the globalization of clinical research. N Engl J Med. 2009;360(8):816-823.

Many of the medical journals read most by hospitalists, including the New England Journal of Medicine and the Journal of the American Medical Association, are adopting a new set of guidelines for the disclosure of potential conflicts of interest, a move the journals and researchers say is a step toward further transparency of authors' competing loyalties.

"From the perspective of an investigator and an end-user of the scientific literature, this is a positive development," says Andrew Masica, MD, MSCI, FHM, director of clinical effectiveness at Baylor Health Care System in Waco, Texas. "In many cases, a work's biggest impact is at the time of its initial release. It is important to provide full information on potential conflicts of interest at this early stage, rather than having something disclosed further down the road."

The new reporting guidelines were introduced in the fall by the International Committee of Medical Journal Editors and are being phased in at member journals. Authors will be asked to disclose four types of information, according to an NEJM editorial:¹

• Financial associations tied to the study they worked on; 
  

   

• Financial ties that could have an "interest in the general area of the submitted manuscript;" 
  

   

• Similar financial associations involving spouses and children under 18 years of age; and
  

   

• Relevant nonfinancial associations.

 

The new rules "align well with the overall trend towards transparency in healthcare," says Dr. Masica, who published this year in the Journal of Hospital Medicine. "Safety and quality data at both the hospital and practitioner level are increasingly available to the public; consistency with disclosure helps move research toward that same standard."

To that end, JHM is updating its peer-review submission Web site to incorporate the new changes and expects to make an announcement on its progress in April. "Transparency is good for healthcare delivery and establishing trust with our primary focus—the care of hospitalized patients," says Mark V. Williams, MD, FACP, FHM, JHM editor-in-chief.

Download the new ICMJE disclosure form and view completed samples.

Reference

1. Glickman SW, McHutchison JG, Peterson ED, et al. Ethical and scientific implications of the globalization of clinical research. N Engl J Med. 2009;360(8):816-823.

Many of the medical journals read most by hospitalists, including the New England Journal of Medicine and the Journal of the American Medical Association, are adopting a new set of guidelines for the disclosure of potential conflicts of interest, a move the journals and researchers say is a step toward further transparency of authors' competing loyalties.

"From the perspective of an investigator and an end-user of the scientific literature, this is a positive development," says Andrew Masica, MD, MSCI, FHM, director of clinical effectiveness at Baylor Health Care System in Waco, Texas. "In many cases, a work's biggest impact is at the time of its initial release. It is important to provide full information on potential conflicts of interest at this early stage, rather than having something disclosed further down the road."

The new reporting guidelines were introduced in the fall by the International Committee of Medical Journal Editors and are being phased in at member journals. Authors will be asked to disclose four types of information, according to an NEJM editorial:¹

• Financial associations tied to the study they worked on; 
  

   

• Financial ties that could have an "interest in the general area of the submitted manuscript;" 
  

   

• Similar financial associations involving spouses and children under 18 years of age; and
  

   

• Relevant nonfinancial associations.

 

The new rules "align well with the overall trend towards transparency in healthcare," says Dr. Masica, who published this year in the Journal of Hospital Medicine. "Safety and quality data at both the hospital and practitioner level are increasingly available to the public; consistency with disclosure helps move research toward that same standard."

To that end, JHM is updating its peer-review submission Web site to incorporate the new changes and expects to make an announcement on its progress in April. "Transparency is good for healthcare delivery and establishing trust with our primary focus—the care of hospitalized patients," says Mark V. Williams, MD, FACP, FHM, JHM editor-in-chief.

Download the new ICMJE disclosure form and view completed samples.

Reference

1. Glickman SW, McHutchison JG, Peterson ED, et al. Ethical and scientific implications of the globalization of clinical research. N Engl J Med. 2009;360(8):816-823.

Hospitalists can buck the tide of physician dissatisfaction in this era of reimbursement uncertainties, productivity pressures, and regulatory burdens.

Here’s fresh evidence: One of the larger HM groups in the U.S.—IPC: The Hospitalist Company Inc.—recently was named one of the "Best Places to Work in Healthcare" by Modern Healthcare. The 2009 rankings were based on employee perceptions of work environment, role satisfaction, leadership and planning, culture and communications, pay and benefits, and other variables.

“Infrastructure support is key to our physicians’ satisfaction,” says IPC founder, chairman, and CEO Adam Singer, MD. A virtual office enables IPC physicians to consult with more than 1,000 colleagues serving close to 500 facilities in 19 states. Extensive business training also helps IPC physicians become proficient in coding and billing, leading meetings, speaking the language of hospital administration, and other business-savvy topics, Dr. Singer says.

Professional respect and autonomy are other chief drivers of satisfaction, according to Douglas W. Carlson, MD, FHM, SHM Career Satisfaction Task Force member. "While compensation is certainly a factor, more important is the recognition hospitalists now receive from colleagues in other specialties who see them as real go-to leaders and experts in hospital-based care," says Dr. Carlson, who is director of the division of Pediatric Hospital Medicine at St. Louis Children's Hospital. Also key, he adds, is the move to shift schedules with more balanced workloads that allow hospitalists to stay intellectually stimulated.

Hospitalists can buck the tide of physician dissatisfaction in this era of reimbursement uncertainties, productivity pressures, and regulatory burdens.

Here’s fresh evidence: One of the larger HM groups in the U.S.—IPC: The Hospitalist Company Inc.—recently was named one of the "Best Places to Work in Healthcare" by Modern Healthcare. The 2009 rankings were based on employee perceptions of work environment, role satisfaction, leadership and planning, culture and communications, pay and benefits, and other variables.

“Infrastructure support is key to our physicians’ satisfaction,” says IPC founder, chairman, and CEO Adam Singer, MD. A virtual office enables IPC physicians to consult with more than 1,000 colleagues serving close to 500 facilities in 19 states. Extensive business training also helps IPC physicians become proficient in coding and billing, leading meetings, speaking the language of hospital administration, and other business-savvy topics, Dr. Singer says.

Professional respect and autonomy are other chief drivers of satisfaction, according to Douglas W. Carlson, MD, FHM, SHM Career Satisfaction Task Force member. "While compensation is certainly a factor, more important is the recognition hospitalists now receive from colleagues in other specialties who see them as real go-to leaders and experts in hospital-based care," says Dr. Carlson, who is director of the division of Pediatric Hospital Medicine at St. Louis Children's Hospital. Also key, he adds, is the move to shift schedules with more balanced workloads that allow hospitalists to stay intellectually stimulated.

Hospitalists can buck the tide of physician dissatisfaction in this era of reimbursement uncertainties, productivity pressures, and regulatory burdens.

Here’s fresh evidence: One of the larger HM groups in the U.S.—IPC: The Hospitalist Company Inc.—recently was named one of the "Best Places to Work in Healthcare" by Modern Healthcare. The 2009 rankings were based on employee perceptions of work environment, role satisfaction, leadership and planning, culture and communications, pay and benefits, and other variables.

“Infrastructure support is key to our physicians’ satisfaction,” says IPC founder, chairman, and CEO Adam Singer, MD. A virtual office enables IPC physicians to consult with more than 1,000 colleagues serving close to 500 facilities in 19 states. Extensive business training also helps IPC physicians become proficient in coding and billing, leading meetings, speaking the language of hospital administration, and other business-savvy topics, Dr. Singer says.

Professional respect and autonomy are other chief drivers of satisfaction, according to Douglas W. Carlson, MD, FHM, SHM Career Satisfaction Task Force member. "While compensation is certainly a factor, more important is the recognition hospitalists now receive from colleagues in other specialties who see them as real go-to leaders and experts in hospital-based care," says Dr. Carlson, who is director of the division of Pediatric Hospital Medicine at St. Louis Children's Hospital. Also key, he adds, is the move to shift schedules with more balanced workloads that allow hospitalists to stay intellectually stimulated.

Sam Schulman, MD

NEW ORLEANS—The direct thrombin inhibitor dabigatran etexilate is a safe, effective anticoagulant that, unlike warfarin, does not require routine monitoring or dose adjustments, according a presentation at 2009 ASH Annual Meeting.

In the past 20 years, research has intensified to find a competitor to warfarin, said Sam Schulman, MD, of McMaster University in Ontario, Canada.

Ximelagatran had been approved in Europe and other countries for the prevention of venous thromboembolis (VTE), but it was withdrawn in 2006 due to the induction of liver problems.

Dabigatran, like ximelagatran, slows down thrombin, Dr Schulman said.

“Dabigatran is an oral drug with quick onset; it works within 1 to 2 hours,” he explained. “There are few interactions of dabigatran with other drugs, and there is no metabolism in the liver. It can be delivered in a fixed dose that does not require monitoring and should make life easier for patients.”

The drug has been approved in Europe and Canada for the prevention of VTE in orthopedic surgery patients and has been studied in atrial fibrillation. 

Dr Schulman led the RE-COVER trial, a randomized, double-blind, trial comparing dabigatran and warfarin in  2539 patients with acute VTE.

Patients were first treated with low-molecular-weight or unfractionated heparin for 5 to 11 days. They then received dabigatran at 150 mg twice daily in a fixed dose (n=1274) or warfarin dose-adjusted to an International Normalized Ratio of 2.0 and 3.0 (n=1265). Patients received treatment for 6 months.

The patient characteristics were well-balanced between the two groups, Dr Shulman said. The patients had a mean age of 55 years and were predominantly Caucasian. There were slightly more men than women. One quarter of the patients had had a previous VTE.

Both groups showed similar treatment improvements. At 6 months, 30 patients (2.4%) taking dabigatran and 27 patients (2.1%) taking warfarin developed new blood clots.

“This is well below the predetermined margin for non-inferiority of dabigatran,” Dr Shulman said.

Subgroup analyses showed dabigatran was just as effective as warfarin.

Safety data showed that 20 patients (1.6%) on dabigatran and 24 patients (1.9%) on warfarin developed major bleeding. There was 1 fatal bleeding episode in each group. In the dabigatran arm, 207 patients experienced any bleeding, compared to 280 patients in the warfarin arm.

Dabigatran also led to a 37% reduction in the risk of clinically relevant bleeding, Dr Shulman said.

There was no difference between the two groups in other major side effects, including myocardial infarction and abnormal liver function tests.

“Dabigatran shows comparable efficacy to warfarin,” Dr Shulman said. “It is as safe as warfarin in terms of bleeding rates. Dabigatran provides a more convenient, fixed-dose treatment for acute VTE with the potential to replace warfarin.”

He added that parallel studies in acute VTE are planned to test dabigatran in a population that includes more Asians. Two studies of extended therapy are planned, one to compare dabigatran to placebo and the other to compare it to warfarin.

Sam Schulman, MD

NEW ORLEANS—The direct thrombin inhibitor dabigatran etexilate is a safe, effective anticoagulant that, unlike warfarin, does not require routine monitoring or dose adjustments, according a presentation at 2009 ASH Annual Meeting.

In the past 20 years, research has intensified to find a competitor to warfarin, said Sam Schulman, MD, of McMaster University in Ontario, Canada.

Ximelagatran had been approved in Europe and other countries for the prevention of venous thromboembolis (VTE), but it was withdrawn in 2006 due to the induction of liver problems.

Dabigatran, like ximelagatran, slows down thrombin, Dr Schulman said.

“Dabigatran is an oral drug with quick onset; it works within 1 to 2 hours,” he explained. “There are few interactions of dabigatran with other drugs, and there is no metabolism in the liver. It can be delivered in a fixed dose that does not require monitoring and should make life easier for patients.”

The drug has been approved in Europe and Canada for the prevention of VTE in orthopedic surgery patients and has been studied in atrial fibrillation. 

Dr Schulman led the RE-COVER trial, a randomized, double-blind, trial comparing dabigatran and warfarin in  2539 patients with acute VTE.

Patients were first treated with low-molecular-weight or unfractionated heparin for 5 to 11 days. They then received dabigatran at 150 mg twice daily in a fixed dose (n=1274) or warfarin dose-adjusted to an International Normalized Ratio of 2.0 and 3.0 (n=1265). Patients received treatment for 6 months.

The patient characteristics were well-balanced between the two groups, Dr Shulman said. The patients had a mean age of 55 years and were predominantly Caucasian. There were slightly more men than women. One quarter of the patients had had a previous VTE.

Both groups showed similar treatment improvements. At 6 months, 30 patients (2.4%) taking dabigatran and 27 patients (2.1%) taking warfarin developed new blood clots.

“This is well below the predetermined margin for non-inferiority of dabigatran,” Dr Shulman said.

Subgroup analyses showed dabigatran was just as effective as warfarin.

Safety data showed that 20 patients (1.6%) on dabigatran and 24 patients (1.9%) on warfarin developed major bleeding. There was 1 fatal bleeding episode in each group. In the dabigatran arm, 207 patients experienced any bleeding, compared to 280 patients in the warfarin arm.

Dabigatran also led to a 37% reduction in the risk of clinically relevant bleeding, Dr Shulman said.

There was no difference between the two groups in other major side effects, including myocardial infarction and abnormal liver function tests.

“Dabigatran shows comparable efficacy to warfarin,” Dr Shulman said. “It is as safe as warfarin in terms of bleeding rates. Dabigatran provides a more convenient, fixed-dose treatment for acute VTE with the potential to replace warfarin.”

He added that parallel studies in acute VTE are planned to test dabigatran in a population that includes more Asians. Two studies of extended therapy are planned, one to compare dabigatran to placebo and the other to compare it to warfarin.

Sam Schulman, MD

NEW ORLEANS—The direct thrombin inhibitor dabigatran etexilate is a safe, effective anticoagulant that, unlike warfarin, does not require routine monitoring or dose adjustments, according a presentation at 2009 ASH Annual Meeting.

In the past 20 years, research has intensified to find a competitor to warfarin, said Sam Schulman, MD, of McMaster University in Ontario, Canada.

Ximelagatran had been approved in Europe and other countries for the prevention of venous thromboembolis (VTE), but it was withdrawn in 2006 due to the induction of liver problems.

Dabigatran, like ximelagatran, slows down thrombin, Dr Schulman said.

“Dabigatran is an oral drug with quick onset; it works within 1 to 2 hours,” he explained. “There are few interactions of dabigatran with other drugs, and there is no metabolism in the liver. It can be delivered in a fixed dose that does not require monitoring and should make life easier for patients.”

The drug has been approved in Europe and Canada for the prevention of VTE in orthopedic surgery patients and has been studied in atrial fibrillation. 

Dr Schulman led the RE-COVER trial, a randomized, double-blind, trial comparing dabigatran and warfarin in  2539 patients with acute VTE.

Patients were first treated with low-molecular-weight or unfractionated heparin for 5 to 11 days. They then received dabigatran at 150 mg twice daily in a fixed dose (n=1274) or warfarin dose-adjusted to an International Normalized Ratio of 2.0 and 3.0 (n=1265). Patients received treatment for 6 months.

The patient characteristics were well-balanced between the two groups, Dr Shulman said. The patients had a mean age of 55 years and were predominantly Caucasian. There were slightly more men than women. One quarter of the patients had had a previous VTE.

Both groups showed similar treatment improvements. At 6 months, 30 patients (2.4%) taking dabigatran and 27 patients (2.1%) taking warfarin developed new blood clots.

“This is well below the predetermined margin for non-inferiority of dabigatran,” Dr Shulman said.

Subgroup analyses showed dabigatran was just as effective as warfarin.

Safety data showed that 20 patients (1.6%) on dabigatran and 24 patients (1.9%) on warfarin developed major bleeding. There was 1 fatal bleeding episode in each group. In the dabigatran arm, 207 patients experienced any bleeding, compared to 280 patients in the warfarin arm.

Dabigatran also led to a 37% reduction in the risk of clinically relevant bleeding, Dr Shulman said.

There was no difference between the two groups in other major side effects, including myocardial infarction and abnormal liver function tests.

“Dabigatran shows comparable efficacy to warfarin,” Dr Shulman said. “It is as safe as warfarin in terms of bleeding rates. Dabigatran provides a more convenient, fixed-dose treatment for acute VTE with the potential to replace warfarin.”

He added that parallel studies in acute VTE are planned to test dabigatran in a population that includes more Asians. Two studies of extended therapy are planned, one to compare dabigatran to placebo and the other to compare it to warfarin.

NEW YORK—Fostamatinib, a potent, specific inhibitor of spleen tyrosine kinase (Syk), shows promise as a targeted therapy for non-Hodgkin’s lymphoma (NHL) and leukemia.

The B-cell receptor is present on both normal B cells and malignant B cells. Signaling through this receptor is necessary for B-cell maturation and survival. A subset of aggressive lymphomas, as well as follicular lymphomas, appear to rely on signaling from this receptor for survival, said Jonathan Friedberg, MD, of the University of Rochester in New York, at the Chemotherapy Foundation Symposium held November 10-13, 2009.

Syk mediates and amplifies the B-cell receptor signal and initiates downstream events. Inhibition of Syk results in lymphoma cell death in vitro, he said.

“Syk is expressed in aggressive B-cell lines. Altered B-cell receptor signaling distinguishes follicular lymphoma cells from non-malignant B cells,” said Dr Friedberg. “Syk activity is increased in follicular lymphoma cells compared to normal cells.”

Fostamatinib is an orally available drug that has been shown to be safe in healthy human volunteers and is active in the treatment of rheumatoid arthritis and idiopathic thrombocytopenic purpura (ITP). A study of 19 ITP patients found the drug was well tolerated and yielded a 75% response rate.

Dr Friedberg presented the results of the first phase 1/2 trial of fostamatinib in heavily pretreated patients with relapsed/refractory NHL. The phase 1 study evaluated 200 mg and 250 mg twice-daily doses of fostamatinib in 13 patients, median age 74 years. The dose-limiting toxicities were neutropenia, thrombocytopenia, and diarrhea. The 200 mg twice-daily dose was chosen for phase 2 testing.

The phase 2 study enrolled 68 patients with relapsed/refractory disease, including diffuse large B-cell lymphoma (DLBCL) (23 patients), follicular lymphoma (21 patients), and other NHLs (24 patients). The other NHLs mainly included patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).

The drug was well tolerated, he said. Adverse events were mainly grade 1 or 2. The most common toxicities included diarrhea, fatigue, cytopenias, nausea, and hypertension. He noted that 20% of patients developed hypertension, which was easily controlled. Five patients developed febrile neutropenia and 1 patient had pancytopenia.

Response rates were 21% for DLBCL patients, 10% for follicular lymphoma patients, 55% for CLL/SLL. Stable disease was observed in an additional 22 patients. Median progression-free survival was 4.2 months and response duration exceeded 4 months.

“Some patients had bulky lymphadenopathy that resolved completely with this agent,” said Dr Friedberg. “As the lymphocyte count increased, the lymph nodes melted away.” White blood cell counts normalized in almost all CLL patients, he noted.

The future development of the drug is likely to include rational combinations with other agents. Ongoing laboratory studies are evaluating fostamatinib with mTOR inhibitors, rituximab, proteasome inhibitors, and chemotherapeutic agents.

“Additional clinical trials are planned to identify lymphomas dependent upon the BCR pathway, and to confirm the exciting effects of this truly targeted therapy for B-cell lymphomas and leukemia,” he said.

NEW YORK—Fostamatinib, a potent, specific inhibitor of spleen tyrosine kinase (Syk), shows promise as a targeted therapy for non-Hodgkin’s lymphoma (NHL) and leukemia.

The B-cell receptor is present on both normal B cells and malignant B cells. Signaling through this receptor is necessary for B-cell maturation and survival. A subset of aggressive lymphomas, as well as follicular lymphomas, appear to rely on signaling from this receptor for survival, said Jonathan Friedberg, MD, of the University of Rochester in New York, at the Chemotherapy Foundation Symposium held November 10-13, 2009.

Syk mediates and amplifies the B-cell receptor signal and initiates downstream events. Inhibition of Syk results in lymphoma cell death in vitro, he said.

“Syk is expressed in aggressive B-cell lines. Altered B-cell receptor signaling distinguishes follicular lymphoma cells from non-malignant B cells,” said Dr Friedberg. “Syk activity is increased in follicular lymphoma cells compared to normal cells.”

Fostamatinib is an orally available drug that has been shown to be safe in healthy human volunteers and is active in the treatment of rheumatoid arthritis and idiopathic thrombocytopenic purpura (ITP). A study of 19 ITP patients found the drug was well tolerated and yielded a 75% response rate.

Dr Friedberg presented the results of the first phase 1/2 trial of fostamatinib in heavily pretreated patients with relapsed/refractory NHL. The phase 1 study evaluated 200 mg and 250 mg twice-daily doses of fostamatinib in 13 patients, median age 74 years. The dose-limiting toxicities were neutropenia, thrombocytopenia, and diarrhea. The 200 mg twice-daily dose was chosen for phase 2 testing.

The phase 2 study enrolled 68 patients with relapsed/refractory disease, including diffuse large B-cell lymphoma (DLBCL) (23 patients), follicular lymphoma (21 patients), and other NHLs (24 patients). The other NHLs mainly included patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).

The drug was well tolerated, he said. Adverse events were mainly grade 1 or 2. The most common toxicities included diarrhea, fatigue, cytopenias, nausea, and hypertension. He noted that 20% of patients developed hypertension, which was easily controlled. Five patients developed febrile neutropenia and 1 patient had pancytopenia.

Response rates were 21% for DLBCL patients, 10% for follicular lymphoma patients, 55% for CLL/SLL. Stable disease was observed in an additional 22 patients. Median progression-free survival was 4.2 months and response duration exceeded 4 months.

“Some patients had bulky lymphadenopathy that resolved completely with this agent,” said Dr Friedberg. “As the lymphocyte count increased, the lymph nodes melted away.” White blood cell counts normalized in almost all CLL patients, he noted.

The future development of the drug is likely to include rational combinations with other agents. Ongoing laboratory studies are evaluating fostamatinib with mTOR inhibitors, rituximab, proteasome inhibitors, and chemotherapeutic agents.

“Additional clinical trials are planned to identify lymphomas dependent upon the BCR pathway, and to confirm the exciting effects of this truly targeted therapy for B-cell lymphomas and leukemia,” he said.

NEW YORK—Fostamatinib, a potent, specific inhibitor of spleen tyrosine kinase (Syk), shows promise as a targeted therapy for non-Hodgkin’s lymphoma (NHL) and leukemia.

The B-cell receptor is present on both normal B cells and malignant B cells. Signaling through this receptor is necessary for B-cell maturation and survival. A subset of aggressive lymphomas, as well as follicular lymphomas, appear to rely on signaling from this receptor for survival, said Jonathan Friedberg, MD, of the University of Rochester in New York, at the Chemotherapy Foundation Symposium held November 10-13, 2009.

Syk mediates and amplifies the B-cell receptor signal and initiates downstream events. Inhibition of Syk results in lymphoma cell death in vitro, he said.

“Syk is expressed in aggressive B-cell lines. Altered B-cell receptor signaling distinguishes follicular lymphoma cells from non-malignant B cells,” said Dr Friedberg. “Syk activity is increased in follicular lymphoma cells compared to normal cells.”

Fostamatinib is an orally available drug that has been shown to be safe in healthy human volunteers and is active in the treatment of rheumatoid arthritis and idiopathic thrombocytopenic purpura (ITP). A study of 19 ITP patients found the drug was well tolerated and yielded a 75% response rate.

Dr Friedberg presented the results of the first phase 1/2 trial of fostamatinib in heavily pretreated patients with relapsed/refractory NHL. The phase 1 study evaluated 200 mg and 250 mg twice-daily doses of fostamatinib in 13 patients, median age 74 years. The dose-limiting toxicities were neutropenia, thrombocytopenia, and diarrhea. The 200 mg twice-daily dose was chosen for phase 2 testing.

The phase 2 study enrolled 68 patients with relapsed/refractory disease, including diffuse large B-cell lymphoma (DLBCL) (23 patients), follicular lymphoma (21 patients), and other NHLs (24 patients). The other NHLs mainly included patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).

The drug was well tolerated, he said. Adverse events were mainly grade 1 or 2. The most common toxicities included diarrhea, fatigue, cytopenias, nausea, and hypertension. He noted that 20% of patients developed hypertension, which was easily controlled. Five patients developed febrile neutropenia and 1 patient had pancytopenia.

Response rates were 21% for DLBCL patients, 10% for follicular lymphoma patients, 55% for CLL/SLL. Stable disease was observed in an additional 22 patients. Median progression-free survival was 4.2 months and response duration exceeded 4 months.

“Some patients had bulky lymphadenopathy that resolved completely with this agent,” said Dr Friedberg. “As the lymphocyte count increased, the lymph nodes melted away.” White blood cell counts normalized in almost all CLL patients, he noted.

The future development of the drug is likely to include rational combinations with other agents. Ongoing laboratory studies are evaluating fostamatinib with mTOR inhibitors, rituximab, proteasome inhibitors, and chemotherapeutic agents.

“Additional clinical trials are planned to identify lymphomas dependent upon the BCR pathway, and to confirm the exciting effects of this truly targeted therapy for B-cell lymphomas and leukemia,” he said.