Other contenders in a novel class of glucose-lowering agents are waiting in the wings, despite a negative reception by the Food and Drug Administration on dapagliflozin – the first in that class of agents – presumably because of concerns noted by an FDA advisory panel about potential increases in the risk of bladder and breast cancers associated with the drug.

On Jan. 19, the drug’s joint developers, Bristol-Myers Squibb and AstraZeneca, announced that it received a complete response from the FDA that asked for still more clinical data on dapagliflozin. Although the companies offered no specifics about the request, they said in a statement that they are working "closely with the FDA to determine the appropriate next steps for the dapagliflozin application."

Dapagliflozin lowers glucose by selectively inhibiting renal glucose reabsorption via inhibition of sodium-glucose cotransporter 2 (SGLT2). It was developed as an insulin-independent treatment approach for type 2 diabetes mellitus, as an adjunct to diet and exercise, as monotherapy, or in combination with other diabetes drugs. Despite the initial FDA panel vote, interest in the drug persists, as it is believed to address a pathogenic defect that has yet to be addressed in diabetes.

Bristol-Myers Squibb and AstraZeneca submitted data from recently completed and ongoing phase III clinical trials of dapagliflozin in response to an FDA request for clarification on the drug’s cancer and hepatic risks, along with further data on efficacy and safety in special populations, including the elderly, minorities, and patients with moderate renal impairment.

"This data submission constitutes a major amendment to the original new drug application (NDA) for dapagliflozin," Dr. Brian Daniels, senior vice president of global development and medical affairs at Bristol-Myers Squibb, explained in a statement last fall.

In July 2011, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee recommended against its approval in a 9-6 vote. Despite the drug’s associated cardiovascular and weight-loss benefits, panel members were troubled by nine cases each of bladder and breast cancer among dapagliflozin-treated patients, compared with one of each type in control patients. Using these numbers, the FDA calculated risk ratios of 5.08 for the incidence of bladder cancer in dapagliflozin-treated men, compared with controls, and 4.04 for the incidence of breast cancer in women. The agency’s decision to deny marketing approval for dapagliflozin was widely expected.

Nevertheless, the pipeline of SGLT2-based drugs is full. At the European Association for the Study of Diabetes (EASD) meeting in September, data were presented on Boehringer Ingelheim’s empagliflozin, Astellas Pharma’s ipragliflozin, Taisho Pharmaceuticals’ TS-071, and Lexicon Pharmaceuticals’ LX4211, which is a dual inhibitor of both SGLT1 and SGLT2. All of these agents showed that they can successfully lower glucose levels and improve other metabolic parameters, with generally good short-term safety profiles. The largest of the study populations was 495 patients (for empagliflozin), and the longest of the study periods was 16 weeks (for ipragliflozin).

In an interview, Dr. Pablo Lapuerta, senior vice president and chief medical officer at Lexicon, noted that as a dual SGLT1/SGLT2 inhibitor, LX4211 is actually in a distinct class from dapagliflozin.

"This differentiates LX4211 from the SGLT2-specific inhibitors in several ways. For example, in patients with type 2 diabetes, LX4211 has been shown to cause a rapid reduction in blood sugar levels after meals, and an increase in GLP-1 [glucagonlike peptide–1] and the increase in PYY [peptide YY], effects that are associated with SGLT1 inhibition by LX4211 in the gastrointestinal tract. Also, recent studies in healthy subjects have shown that LX4211 substantially decreases postprandial glucose levels without hypoglycemia, and in both diabetic patients and healthy subjects, LX4211 can substantially reduce triglycerides. These results have not been reported for SGLT2-selective inhibitors," he said.

With regard to safety, Dr. Lapuerta noted that the "issue for the FDA advisory committee had to do with the overall benefit/risk profile of dapagliflozin. We believe the solution will involve addressing both benefits and risks. On the benefit side, we believe that LX4211 is a cardiovascular drug, not just a diabetes drug. Dual inhibition of SGLT1/2 with LX4211 offers the potential benefit to combine strong [hemoglobin] A_1c reduction with benefits in blood pressure, uric acid, weight loss, and triglycerides. Cardiovascular benefits will be relevant to approval," he said.

"On the risk side, there is the potential that reports of bladder cancer on dapagliflozin reflected an ascertainment bias. We can address this in the LX4211 clinical program by ensuring that we carefully document physician referral patterns and take steps to ensure [that] our studies identify as much as possible new conditions instead of preexisting ones."

Susan Holz, public relations manager at Boehringer Ingelheim Pharmaceuticals, said in an earlier interview, "We are aware of the advisory committee’s concerns with dapagliflozin and are working with the FDA to ensure [that] our filing package for empagliflozin is robust and comprehensive. Phase III trials for empagliflozin are underway, and we are continuing to evaluate the drug’s safety profile." Currently, there are 11 ongoing, multinational, phase III clinical trials, including a large cardiovascular outcomes safety trial, she said.

At the EASD meeting in September, Dr. Michaela Diamant, scientific director of the diabetes center at Free University Medical Center in Amsterdam, commented that SGLT2 inhibitors have "an interesting mechanism that addresses, to a certain extent, a pathogenic defect that has been largely overlooked in diabetes. ... I’m sure there is a huge group of patients who can profit from these novel agents."

Regarding the safety issue, she asked, "If you would have a trial of 2-5 years, would you definitely address causality of cancer? We know that cancer development takes 20 years. It’s very unlikely that the drug caused cancer. We have to do what is feasible. The industry is not going to develop any more of these drugs if they are required to do a trial of 10 years. It’s difficult to tease out [contributors] to the development of cancer," Dr. Diamant continued.

Dr. Diamant has been a board member, advisory panel member, consultant, research support recipient, and/or speakers bureau participant for Eli Lilly, Merck Sharp & Dohme, Novo Nordisk, Abbott, AstraZeneca/BMS, Boehringer Ingelheim, Poxel Pharma, Sanofi-Aventis, Amylin Pharmaceuticals, Novartis, and Takeda.

Sue Sutter of "The Pink Sheet" contributed to this story. "The Pink Sheet" and this publication are both owned by Elsevier.

Other contenders in a novel class of glucose-lowering agents are waiting in the wings, despite a negative reception by the Food and Drug Administration on dapagliflozin – the first in that class of agents – presumably because of concerns noted by an FDA advisory panel about potential increases in the risk of bladder and breast cancers associated with the drug.

On Jan. 19, the drug’s joint developers, Bristol-Myers Squibb and AstraZeneca, announced that it received a complete response from the FDA that asked for still more clinical data on dapagliflozin. Although the companies offered no specifics about the request, they said in a statement that they are working "closely with the FDA to determine the appropriate next steps for the dapagliflozin application."

Dapagliflozin lowers glucose by selectively inhibiting renal glucose reabsorption via inhibition of sodium-glucose cotransporter 2 (SGLT2). It was developed as an insulin-independent treatment approach for type 2 diabetes mellitus, as an adjunct to diet and exercise, as monotherapy, or in combination with other diabetes drugs. Despite the initial FDA panel vote, interest in the drug persists, as it is believed to address a pathogenic defect that has yet to be addressed in diabetes.

Bristol-Myers Squibb and AstraZeneca submitted data from recently completed and ongoing phase III clinical trials of dapagliflozin in response to an FDA request for clarification on the drug’s cancer and hepatic risks, along with further data on efficacy and safety in special populations, including the elderly, minorities, and patients with moderate renal impairment.

"This data submission constitutes a major amendment to the original new drug application (NDA) for dapagliflozin," Dr. Brian Daniels, senior vice president of global development and medical affairs at Bristol-Myers Squibb, explained in a statement last fall.

In July 2011, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee recommended against its approval in a 9-6 vote. Despite the drug’s associated cardiovascular and weight-loss benefits, panel members were troubled by nine cases each of bladder and breast cancer among dapagliflozin-treated patients, compared with one of each type in control patients. Using these numbers, the FDA calculated risk ratios of 5.08 for the incidence of bladder cancer in dapagliflozin-treated men, compared with controls, and 4.04 for the incidence of breast cancer in women. The agency’s decision to deny marketing approval for dapagliflozin was widely expected.

Nevertheless, the pipeline of SGLT2-based drugs is full. At the European Association for the Study of Diabetes (EASD) meeting in September, data were presented on Boehringer Ingelheim’s empagliflozin, Astellas Pharma’s ipragliflozin, Taisho Pharmaceuticals’ TS-071, and Lexicon Pharmaceuticals’ LX4211, which is a dual inhibitor of both SGLT1 and SGLT2. All of these agents showed that they can successfully lower glucose levels and improve other metabolic parameters, with generally good short-term safety profiles. The largest of the study populations was 495 patients (for empagliflozin), and the longest of the study periods was 16 weeks (for ipragliflozin).

In an interview, Dr. Pablo Lapuerta, senior vice president and chief medical officer at Lexicon, noted that as a dual SGLT1/SGLT2 inhibitor, LX4211 is actually in a distinct class from dapagliflozin.

"This differentiates LX4211 from the SGLT2-specific inhibitors in several ways. For example, in patients with type 2 diabetes, LX4211 has been shown to cause a rapid reduction in blood sugar levels after meals, and an increase in GLP-1 [glucagonlike peptide–1] and the increase in PYY [peptide YY], effects that are associated with SGLT1 inhibition by LX4211 in the gastrointestinal tract. Also, recent studies in healthy subjects have shown that LX4211 substantially decreases postprandial glucose levels without hypoglycemia, and in both diabetic patients and healthy subjects, LX4211 can substantially reduce triglycerides. These results have not been reported for SGLT2-selective inhibitors," he said.

With regard to safety, Dr. Lapuerta noted that the "issue for the FDA advisory committee had to do with the overall benefit/risk profile of dapagliflozin. We believe the solution will involve addressing both benefits and risks. On the benefit side, we believe that LX4211 is a cardiovascular drug, not just a diabetes drug. Dual inhibition of SGLT1/2 with LX4211 offers the potential benefit to combine strong [hemoglobin] A_1c reduction with benefits in blood pressure, uric acid, weight loss, and triglycerides. Cardiovascular benefits will be relevant to approval," he said.

"On the risk side, there is the potential that reports of bladder cancer on dapagliflozin reflected an ascertainment bias. We can address this in the LX4211 clinical program by ensuring that we carefully document physician referral patterns and take steps to ensure [that] our studies identify as much as possible new conditions instead of preexisting ones."

Susan Holz, public relations manager at Boehringer Ingelheim Pharmaceuticals, said in an earlier interview, "We are aware of the advisory committee’s concerns with dapagliflozin and are working with the FDA to ensure [that] our filing package for empagliflozin is robust and comprehensive. Phase III trials for empagliflozin are underway, and we are continuing to evaluate the drug’s safety profile." Currently, there are 11 ongoing, multinational, phase III clinical trials, including a large cardiovascular outcomes safety trial, she said.

At the EASD meeting in September, Dr. Michaela Diamant, scientific director of the diabetes center at Free University Medical Center in Amsterdam, commented that SGLT2 inhibitors have "an interesting mechanism that addresses, to a certain extent, a pathogenic defect that has been largely overlooked in diabetes. ... I’m sure there is a huge group of patients who can profit from these novel agents."

Regarding the safety issue, she asked, "If you would have a trial of 2-5 years, would you definitely address causality of cancer? We know that cancer development takes 20 years. It’s very unlikely that the drug caused cancer. We have to do what is feasible. The industry is not going to develop any more of these drugs if they are required to do a trial of 10 years. It’s difficult to tease out [contributors] to the development of cancer," Dr. Diamant continued.

Dr. Diamant has been a board member, advisory panel member, consultant, research support recipient, and/or speakers bureau participant for Eli Lilly, Merck Sharp & Dohme, Novo Nordisk, Abbott, AstraZeneca/BMS, Boehringer Ingelheim, Poxel Pharma, Sanofi-Aventis, Amylin Pharmaceuticals, Novartis, and Takeda.

Sue Sutter of "The Pink Sheet" contributed to this story. "The Pink Sheet" and this publication are both owned by Elsevier.

Other contenders in a novel class of glucose-lowering agents are waiting in the wings, despite a negative reception by the Food and Drug Administration on dapagliflozin – the first in that class of agents – presumably because of concerns noted by an FDA advisory panel about potential increases in the risk of bladder and breast cancers associated with the drug.

On Jan. 19, the drug’s joint developers, Bristol-Myers Squibb and AstraZeneca, announced that it received a complete response from the FDA that asked for still more clinical data on dapagliflozin. Although the companies offered no specifics about the request, they said in a statement that they are working "closely with the FDA to determine the appropriate next steps for the dapagliflozin application."

Dapagliflozin lowers glucose by selectively inhibiting renal glucose reabsorption via inhibition of sodium-glucose cotransporter 2 (SGLT2). It was developed as an insulin-independent treatment approach for type 2 diabetes mellitus, as an adjunct to diet and exercise, as monotherapy, or in combination with other diabetes drugs. Despite the initial FDA panel vote, interest in the drug persists, as it is believed to address a pathogenic defect that has yet to be addressed in diabetes.

Bristol-Myers Squibb and AstraZeneca submitted data from recently completed and ongoing phase III clinical trials of dapagliflozin in response to an FDA request for clarification on the drug’s cancer and hepatic risks, along with further data on efficacy and safety in special populations, including the elderly, minorities, and patients with moderate renal impairment.

"This data submission constitutes a major amendment to the original new drug application (NDA) for dapagliflozin," Dr. Brian Daniels, senior vice president of global development and medical affairs at Bristol-Myers Squibb, explained in a statement last fall.

In July 2011, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee recommended against its approval in a 9-6 vote. Despite the drug’s associated cardiovascular and weight-loss benefits, panel members were troubled by nine cases each of bladder and breast cancer among dapagliflozin-treated patients, compared with one of each type in control patients. Using these numbers, the FDA calculated risk ratios of 5.08 for the incidence of bladder cancer in dapagliflozin-treated men, compared with controls, and 4.04 for the incidence of breast cancer in women. The agency’s decision to deny marketing approval for dapagliflozin was widely expected.

Nevertheless, the pipeline of SGLT2-based drugs is full. At the European Association for the Study of Diabetes (EASD) meeting in September, data were presented on Boehringer Ingelheim’s empagliflozin, Astellas Pharma’s ipragliflozin, Taisho Pharmaceuticals’ TS-071, and Lexicon Pharmaceuticals’ LX4211, which is a dual inhibitor of both SGLT1 and SGLT2. All of these agents showed that they can successfully lower glucose levels and improve other metabolic parameters, with generally good short-term safety profiles. The largest of the study populations was 495 patients (for empagliflozin), and the longest of the study periods was 16 weeks (for ipragliflozin).

In an interview, Dr. Pablo Lapuerta, senior vice president and chief medical officer at Lexicon, noted that as a dual SGLT1/SGLT2 inhibitor, LX4211 is actually in a distinct class from dapagliflozin.

"This differentiates LX4211 from the SGLT2-specific inhibitors in several ways. For example, in patients with type 2 diabetes, LX4211 has been shown to cause a rapid reduction in blood sugar levels after meals, and an increase in GLP-1 [glucagonlike peptide–1] and the increase in PYY [peptide YY], effects that are associated with SGLT1 inhibition by LX4211 in the gastrointestinal tract. Also, recent studies in healthy subjects have shown that LX4211 substantially decreases postprandial glucose levels without hypoglycemia, and in both diabetic patients and healthy subjects, LX4211 can substantially reduce triglycerides. These results have not been reported for SGLT2-selective inhibitors," he said.

With regard to safety, Dr. Lapuerta noted that the "issue for the FDA advisory committee had to do with the overall benefit/risk profile of dapagliflozin. We believe the solution will involve addressing both benefits and risks. On the benefit side, we believe that LX4211 is a cardiovascular drug, not just a diabetes drug. Dual inhibition of SGLT1/2 with LX4211 offers the potential benefit to combine strong [hemoglobin] A_1c reduction with benefits in blood pressure, uric acid, weight loss, and triglycerides. Cardiovascular benefits will be relevant to approval," he said.

"On the risk side, there is the potential that reports of bladder cancer on dapagliflozin reflected an ascertainment bias. We can address this in the LX4211 clinical program by ensuring that we carefully document physician referral patterns and take steps to ensure [that] our studies identify as much as possible new conditions instead of preexisting ones."

Susan Holz, public relations manager at Boehringer Ingelheim Pharmaceuticals, said in an earlier interview, "We are aware of the advisory committee’s concerns with dapagliflozin and are working with the FDA to ensure [that] our filing package for empagliflozin is robust and comprehensive. Phase III trials for empagliflozin are underway, and we are continuing to evaluate the drug’s safety profile." Currently, there are 11 ongoing, multinational, phase III clinical trials, including a large cardiovascular outcomes safety trial, she said.

At the EASD meeting in September, Dr. Michaela Diamant, scientific director of the diabetes center at Free University Medical Center in Amsterdam, commented that SGLT2 inhibitors have "an interesting mechanism that addresses, to a certain extent, a pathogenic defect that has been largely overlooked in diabetes. ... I’m sure there is a huge group of patients who can profit from these novel agents."

Regarding the safety issue, she asked, "If you would have a trial of 2-5 years, would you definitely address causality of cancer? We know that cancer development takes 20 years. It’s very unlikely that the drug caused cancer. We have to do what is feasible. The industry is not going to develop any more of these drugs if they are required to do a trial of 10 years. It’s difficult to tease out [contributors] to the development of cancer," Dr. Diamant continued.

Dr. Diamant has been a board member, advisory panel member, consultant, research support recipient, and/or speakers bureau participant for Eli Lilly, Merck Sharp & Dohme, Novo Nordisk, Abbott, AstraZeneca/BMS, Boehringer Ingelheim, Poxel Pharma, Sanofi-Aventis, Amylin Pharmaceuticals, Novartis, and Takeda.

Sue Sutter of "The Pink Sheet" contributed to this story. "The Pink Sheet" and this publication are both owned by Elsevier.

A hospitalist who works for one of the 32 organizations tapped in the inaugural cohort of Pioneer Accountable Care Organizations (ACOs) says HM should not expect major change in the short term from the new coordinated care model. But change will come in the long term.

"As we start to get data back and start to figure out where we can make the biggest positive impact on improving health for patients and also the impact of cost savings, then the hospitalist will be more involved," says Tierza Stephan, MD, FACP, SFHM, district medical director for hospitalists at Allina Hospitals & Clinics of Minneapolis.

The Pioneer designation was a Centers for Medicare & Medicaid Services (CMS) Innovation Center initiative crafted last summer for organizations and providers already experienced in providing coordinated care. A related model, the Medicare Shared Savings Program, does not require any previous experience with such contracts. The models set benchmarks for providers and institutions to qualify for shared shavings.

Dr. Stephan, a member of SHM's Practice Analysis Committee, helped the Allina Integrated Medical (AIM) Network become one of the Pioneer ACOs. The network includes 1,100 Allina doctors and 900 independent physicians from private clinics or practices. She says Allina has spent months preparing for the ACO: crafting its initial quality metrics, including generic drug utilization, timely turnaround of critical results, and patient satisfaction.

While all members of the network will share data to achieve better efficiency and cost savings, Dr. Stephan says it's too early in the process to say how well the program will work in practice. In the short term, she expects little daily change for HM physicians. Given the time it takes to get a program started, Dr. Stephan urges HM group leaders working on building an ACO, or those already in an approved program, to be a loud voice during the process.

"We're the primary care in the hospital, and primary care is really at the heart of accountable-care organizations," she says. "It really takes commitment by the entire healthcare community, and hospitalists interact with the entire healthcare community."

A hospitalist who works for one of the 32 organizations tapped in the inaugural cohort of Pioneer Accountable Care Organizations (ACOs) says HM should not expect major change in the short term from the new coordinated care model. But change will come in the long term.

"As we start to get data back and start to figure out where we can make the biggest positive impact on improving health for patients and also the impact of cost savings, then the hospitalist will be more involved," says Tierza Stephan, MD, FACP, SFHM, district medical director for hospitalists at Allina Hospitals & Clinics of Minneapolis.

The Pioneer designation was a Centers for Medicare & Medicaid Services (CMS) Innovation Center initiative crafted last summer for organizations and providers already experienced in providing coordinated care. A related model, the Medicare Shared Savings Program, does not require any previous experience with such contracts. The models set benchmarks for providers and institutions to qualify for shared shavings.

Dr. Stephan, a member of SHM's Practice Analysis Committee, helped the Allina Integrated Medical (AIM) Network become one of the Pioneer ACOs. The network includes 1,100 Allina doctors and 900 independent physicians from private clinics or practices. She says Allina has spent months preparing for the ACO: crafting its initial quality metrics, including generic drug utilization, timely turnaround of critical results, and patient satisfaction.

While all members of the network will share data to achieve better efficiency and cost savings, Dr. Stephan says it's too early in the process to say how well the program will work in practice. In the short term, she expects little daily change for HM physicians. Given the time it takes to get a program started, Dr. Stephan urges HM group leaders working on building an ACO, or those already in an approved program, to be a loud voice during the process.

"We're the primary care in the hospital, and primary care is really at the heart of accountable-care organizations," she says. "It really takes commitment by the entire healthcare community, and hospitalists interact with the entire healthcare community."

A hospitalist who works for one of the 32 organizations tapped in the inaugural cohort of Pioneer Accountable Care Organizations (ACOs) says HM should not expect major change in the short term from the new coordinated care model. But change will come in the long term.

"As we start to get data back and start to figure out where we can make the biggest positive impact on improving health for patients and also the impact of cost savings, then the hospitalist will be more involved," says Tierza Stephan, MD, FACP, SFHM, district medical director for hospitalists at Allina Hospitals & Clinics of Minneapolis.

The Pioneer designation was a Centers for Medicare & Medicaid Services (CMS) Innovation Center initiative crafted last summer for organizations and providers already experienced in providing coordinated care. A related model, the Medicare Shared Savings Program, does not require any previous experience with such contracts. The models set benchmarks for providers and institutions to qualify for shared shavings.

Dr. Stephan, a member of SHM's Practice Analysis Committee, helped the Allina Integrated Medical (AIM) Network become one of the Pioneer ACOs. The network includes 1,100 Allina doctors and 900 independent physicians from private clinics or practices. She says Allina has spent months preparing for the ACO: crafting its initial quality metrics, including generic drug utilization, timely turnaround of critical results, and patient satisfaction.

While all members of the network will share data to achieve better efficiency and cost savings, Dr. Stephan says it's too early in the process to say how well the program will work in practice. In the short term, she expects little daily change for HM physicians. Given the time it takes to get a program started, Dr. Stephan urges HM group leaders working on building an ACO, or those already in an approved program, to be a loud voice during the process.

"We're the primary care in the hospital, and primary care is really at the heart of accountable-care organizations," she says. "It really takes commitment by the entire healthcare community, and hospitalists interact with the entire healthcare community."

Piedmont Hospital in Atlanta is one of several hospitals participating in SHM’s care-transitions initiative Project BOOST (Better Outcomes for Older Adults through Safe Transitions) to be included in the first round of Community-Based Care Transitions Project (CCTP) awards.

Matthew Schreiber, MD, vice president and chief medical officer for Piedmont Hospital, says hospitalists should look for ways to participate in the community coalitions applying for CCTP awards, because managing their hospitals’ readmissions rates eventually will be essential to their job security.

“I said to my hospital, ‘Right now, people are giving out money for us to be in the figuring-it-out mode regarding readmissions,” Dr. Schreiber explains. “Eventually, we’ll just have to do it anyway.’”

CCTP is part of the government’s efforts (PDF) to reduce hospital readmissions by encouraging coalitions of health providers to collaborate on care transitions and ongoing care coordination after patients leave the hospital. The $500 million program initially dished out seven awards to community-based coalitions, not directly to hospitals. Most of these coalitions are housed at regional Agencies on Aging and involve multiple hospitals or health systems.

According to the Centers for Medicare & Medicaid Services (CMS), CCTP differs from a traditional grant program in that it pays community-based organizations an all-inclusive rate per eligible discharge, based on the cost of care transition services and of systemic changes at the hospital level.

The seven awardees also employ the Care Transitions Intervention program developed by Eric Coleman, MD, MPH, of the University of Colorado, co-chair of Project BOOST’s national advisory board. The intervention program is a recognized tool for improving care transitions and reducing preventable rehospitalizations through the use of social worker "transition coaches" to provide discharged patients with self-care education and encouragement.

Other BOOST site hospitals participating in CCTP-awarded coalitions include Northwestern Memorial in Chicago and Emory University Hospital Midtown in Atlanta.

Dr. Schreiber says being a Project BOOST site and using Dr. Coleman's Care Transitions Intervention should be complementary for any hospital striving to reduce readmissions. “Both together were greater than the sum of their parts,” he says, adding that Piedmont has reduced its readmission rate by 50%.

Summaries of the first seven sites and information on how to apply for ongoing CCTP grants can be found here.

Piedmont Hospital in Atlanta is one of several hospitals participating in SHM’s care-transitions initiative Project BOOST (Better Outcomes for Older Adults through Safe Transitions) to be included in the first round of Community-Based Care Transitions Project (CCTP) awards.

Matthew Schreiber, MD, vice president and chief medical officer for Piedmont Hospital, says hospitalists should look for ways to participate in the community coalitions applying for CCTP awards, because managing their hospitals’ readmissions rates eventually will be essential to their job security.

“I said to my hospital, ‘Right now, people are giving out money for us to be in the figuring-it-out mode regarding readmissions,” Dr. Schreiber explains. “Eventually, we’ll just have to do it anyway.’”

CCTP is part of the government’s efforts (PDF) to reduce hospital readmissions by encouraging coalitions of health providers to collaborate on care transitions and ongoing care coordination after patients leave the hospital. The $500 million program initially dished out seven awards to community-based coalitions, not directly to hospitals. Most of these coalitions are housed at regional Agencies on Aging and involve multiple hospitals or health systems.

According to the Centers for Medicare & Medicaid Services (CMS), CCTP differs from a traditional grant program in that it pays community-based organizations an all-inclusive rate per eligible discharge, based on the cost of care transition services and of systemic changes at the hospital level.

The seven awardees also employ the Care Transitions Intervention program developed by Eric Coleman, MD, MPH, of the University of Colorado, co-chair of Project BOOST’s national advisory board. The intervention program is a recognized tool for improving care transitions and reducing preventable rehospitalizations through the use of social worker "transition coaches" to provide discharged patients with self-care education and encouragement.

Other BOOST site hospitals participating in CCTP-awarded coalitions include Northwestern Memorial in Chicago and Emory University Hospital Midtown in Atlanta.

Dr. Schreiber says being a Project BOOST site and using Dr. Coleman's Care Transitions Intervention should be complementary for any hospital striving to reduce readmissions. “Both together were greater than the sum of their parts,” he says, adding that Piedmont has reduced its readmission rate by 50%.

Summaries of the first seven sites and information on how to apply for ongoing CCTP grants can be found here.

Piedmont Hospital in Atlanta is one of several hospitals participating in SHM’s care-transitions initiative Project BOOST (Better Outcomes for Older Adults through Safe Transitions) to be included in the first round of Community-Based Care Transitions Project (CCTP) awards.

Matthew Schreiber, MD, vice president and chief medical officer for Piedmont Hospital, says hospitalists should look for ways to participate in the community coalitions applying for CCTP awards, because managing their hospitals’ readmissions rates eventually will be essential to their job security.

“I said to my hospital, ‘Right now, people are giving out money for us to be in the figuring-it-out mode regarding readmissions,” Dr. Schreiber explains. “Eventually, we’ll just have to do it anyway.’”

CCTP is part of the government’s efforts (PDF) to reduce hospital readmissions by encouraging coalitions of health providers to collaborate on care transitions and ongoing care coordination after patients leave the hospital. The $500 million program initially dished out seven awards to community-based coalitions, not directly to hospitals. Most of these coalitions are housed at regional Agencies on Aging and involve multiple hospitals or health systems.

According to the Centers for Medicare & Medicaid Services (CMS), CCTP differs from a traditional grant program in that it pays community-based organizations an all-inclusive rate per eligible discharge, based on the cost of care transition services and of systemic changes at the hospital level.

The seven awardees also employ the Care Transitions Intervention program developed by Eric Coleman, MD, MPH, of the University of Colorado, co-chair of Project BOOST’s national advisory board. The intervention program is a recognized tool for improving care transitions and reducing preventable rehospitalizations through the use of social worker "transition coaches" to provide discharged patients with self-care education and encouragement.

Other BOOST site hospitals participating in CCTP-awarded coalitions include Northwestern Memorial in Chicago and Emory University Hospital Midtown in Atlanta.

Dr. Schreiber says being a Project BOOST site and using Dr. Coleman's Care Transitions Intervention should be complementary for any hospital striving to reduce readmissions. “Both together were greater than the sum of their parts,” he says, adding that Piedmont has reduced its readmission rate by 50%.

Summaries of the first seven sites and information on how to apply for ongoing CCTP grants can be found here.

The prevalence of obesity in the United States appears to have plateaued, according to data from the 2009-2010 National Health and Nutrition Examination Survey (NHANES) conducted by the U.S. Centers for Disease Control and Prevention.

Following dramatic increases in the prevalence of obesity in adults, children, and adolescents in the 1980s and 1990s, as well as changes in the distribution of body mass index, no significant changes were seen in 2009-2010, compared with 2003-2008 figures in adults, and compared with 2007-2008 prevalence rates in children and adolescents.

© okeyphotos/iStockphoto.com

For example, based on data from the 5,926 men and women with measured weight and height who participated in the 2009-2010 NHANES, the age-adjusted prevalence of obesity was roughly 35% for both men and women, which was not significantly different overall compared with the prevalence from 2003-2008, Katherine M. Flegal, Ph.D., and her colleagues from the National Center for Health Statistics, CDC, Hyattsville, Md., report online in the Jan. 17 JAMA.

Despite the lack of change overall, the analysis of adult data did indicate, however, that obesity increased in certain segments of the population. While no significant increase was seen among women overall (age- and race-adjusted annual change in odds ratio from 1999-2010, 1.01), statistically significant increases were seen among non-Hispanic black women (OR, 1.03) and Mexican American women (1.03), the investigators noted (JAMA 2012 Jan. 17 [doi:10.1001/jama.2012.39]).

A significant linear trend was also seen in men over the 12-year period (annual change in OR, 1.04).

As for BMI, the age-adjusted mean in both men and women was 28.7, and the trends over time in this study were similar to those seen with obesity, with a significant increase seen in men, but not in women, over the 12 years, the investigators said.

In a separate cross-sectional analysis of data from 4,111 children and adolescents who participated in NHANES, the 2009-2010 obesity prevalence of 9.7% in infants and toddlers up to age 2 years, and 16.9% for those aged 2-19 years, did not differ significantly from the 2007-2008 prevalence, and no difference was seen between males and females in regard to obesity prevalence, Cynthia L. Ogden, Ph.D., and her colleagues, also from the National Center for Health Statistics, CDC, reported in the same issue of JAMA.

A trend analysis over the 12-year study period did indicate, however, that the obesity prevalence among males aged 2-19 years increased significantly between 1999-2000 and 2009-2010 (OR, 1.05) per 2-year survey cycle, and that there was a significant increasing trend for non-Hispanic black males (OR, 1.10). Also, BMI increased significantly in males aged 12 through 19 years (JAMA 2012 Jan. 17 [doi:10.1001/jama.2012.40]).

NHANES data have been collected continuously since 1999, with reports released in 2-year cycles. Since no universally agreed upon definition of obesity exists for infants and toddlers up to age 2 years, high weight in this age group was defined as weight-for-recumbent length at or above the 95th percentile on the CDCs 2000 growth charts, the investigators explained.

Weight status in those aged 2 through 19 years is defined based on BMI; those at or above the sex-specific 85th percentile, but less than the 95th percentile, are considered overweight, and those at or above the sex-specific 95th percentile are considered obese. For adults, those with a BMI of 25.0 to 29.9 are considered overweight, and those with a BMI of 30.0 or higher are considered obese, with further subdivision into grades 1, 2, and 3 obesity based on BMI of 30.0 to less than 35.0, 35.0 to less than 40.0, and 40.0 or greater, respectively.

Investigators for both analyses noted that it is important to keep in mind that BMI is an "imperfect measure of body fat."

Since racial and ethnic differences in the level of body fat at specific BMIs exist, the differences in obesity prevalence by race and ethnicity in these studies may not represent actual differences in body fat, they said.

Overall, the findings in both adults and children/adolescents suggest that increases in the prevalence of obesity that have previously been observed are not continuing and have leveled off.

Although it’s difficult to predict whether these trends will continue in the same direction, the findings suggest that previous models that predict continuing increases in obesity prevalence in all age groups may be based on invalid assumptions.

None of the authors indicated having relevant conflicts of interest.

The prevalence of obesity in the United States appears to have plateaued, according to data from the 2009-2010 National Health and Nutrition Examination Survey (NHANES) conducted by the U.S. Centers for Disease Control and Prevention.

Following dramatic increases in the prevalence of obesity in adults, children, and adolescents in the 1980s and 1990s, as well as changes in the distribution of body mass index, no significant changes were seen in 2009-2010, compared with 2003-2008 figures in adults, and compared with 2007-2008 prevalence rates in children and adolescents.

© okeyphotos/iStockphoto.com

For example, based on data from the 5,926 men and women with measured weight and height who participated in the 2009-2010 NHANES, the age-adjusted prevalence of obesity was roughly 35% for both men and women, which was not significantly different overall compared with the prevalence from 2003-2008, Katherine M. Flegal, Ph.D., and her colleagues from the National Center for Health Statistics, CDC, Hyattsville, Md., report online in the Jan. 17 JAMA.

Despite the lack of change overall, the analysis of adult data did indicate, however, that obesity increased in certain segments of the population. While no significant increase was seen among women overall (age- and race-adjusted annual change in odds ratio from 1999-2010, 1.01), statistically significant increases were seen among non-Hispanic black women (OR, 1.03) and Mexican American women (1.03), the investigators noted (JAMA 2012 Jan. 17 [doi:10.1001/jama.2012.39]).

A significant linear trend was also seen in men over the 12-year period (annual change in OR, 1.04).

As for BMI, the age-adjusted mean in both men and women was 28.7, and the trends over time in this study were similar to those seen with obesity, with a significant increase seen in men, but not in women, over the 12 years, the investigators said.

In a separate cross-sectional analysis of data from 4,111 children and adolescents who participated in NHANES, the 2009-2010 obesity prevalence of 9.7% in infants and toddlers up to age 2 years, and 16.9% for those aged 2-19 years, did not differ significantly from the 2007-2008 prevalence, and no difference was seen between males and females in regard to obesity prevalence, Cynthia L. Ogden, Ph.D., and her colleagues, also from the National Center for Health Statistics, CDC, reported in the same issue of JAMA.

A trend analysis over the 12-year study period did indicate, however, that the obesity prevalence among males aged 2-19 years increased significantly between 1999-2000 and 2009-2010 (OR, 1.05) per 2-year survey cycle, and that there was a significant increasing trend for non-Hispanic black males (OR, 1.10). Also, BMI increased significantly in males aged 12 through 19 years (JAMA 2012 Jan. 17 [doi:10.1001/jama.2012.40]).

NHANES data have been collected continuously since 1999, with reports released in 2-year cycles. Since no universally agreed upon definition of obesity exists for infants and toddlers up to age 2 years, high weight in this age group was defined as weight-for-recumbent length at or above the 95th percentile on the CDCs 2000 growth charts, the investigators explained.

Weight status in those aged 2 through 19 years is defined based on BMI; those at or above the sex-specific 85th percentile, but less than the 95th percentile, are considered overweight, and those at or above the sex-specific 95th percentile are considered obese. For adults, those with a BMI of 25.0 to 29.9 are considered overweight, and those with a BMI of 30.0 or higher are considered obese, with further subdivision into grades 1, 2, and 3 obesity based on BMI of 30.0 to less than 35.0, 35.0 to less than 40.0, and 40.0 or greater, respectively.

Investigators for both analyses noted that it is important to keep in mind that BMI is an "imperfect measure of body fat."

Since racial and ethnic differences in the level of body fat at specific BMIs exist, the differences in obesity prevalence by race and ethnicity in these studies may not represent actual differences in body fat, they said.

Overall, the findings in both adults and children/adolescents suggest that increases in the prevalence of obesity that have previously been observed are not continuing and have leveled off.

Although it’s difficult to predict whether these trends will continue in the same direction, the findings suggest that previous models that predict continuing increases in obesity prevalence in all age groups may be based on invalid assumptions.

None of the authors indicated having relevant conflicts of interest.

The prevalence of obesity in the United States appears to have plateaued, according to data from the 2009-2010 National Health and Nutrition Examination Survey (NHANES) conducted by the U.S. Centers for Disease Control and Prevention.

Following dramatic increases in the prevalence of obesity in adults, children, and adolescents in the 1980s and 1990s, as well as changes in the distribution of body mass index, no significant changes were seen in 2009-2010, compared with 2003-2008 figures in adults, and compared with 2007-2008 prevalence rates in children and adolescents.

© okeyphotos/iStockphoto.com

For example, based on data from the 5,926 men and women with measured weight and height who participated in the 2009-2010 NHANES, the age-adjusted prevalence of obesity was roughly 35% for both men and women, which was not significantly different overall compared with the prevalence from 2003-2008, Katherine M. Flegal, Ph.D., and her colleagues from the National Center for Health Statistics, CDC, Hyattsville, Md., report online in the Jan. 17 JAMA.

Despite the lack of change overall, the analysis of adult data did indicate, however, that obesity increased in certain segments of the population. While no significant increase was seen among women overall (age- and race-adjusted annual change in odds ratio from 1999-2010, 1.01), statistically significant increases were seen among non-Hispanic black women (OR, 1.03) and Mexican American women (1.03), the investigators noted (JAMA 2012 Jan. 17 [doi:10.1001/jama.2012.39]).

A significant linear trend was also seen in men over the 12-year period (annual change in OR, 1.04).

As for BMI, the age-adjusted mean in both men and women was 28.7, and the trends over time in this study were similar to those seen with obesity, with a significant increase seen in men, but not in women, over the 12 years, the investigators said.

In a separate cross-sectional analysis of data from 4,111 children and adolescents who participated in NHANES, the 2009-2010 obesity prevalence of 9.7% in infants and toddlers up to age 2 years, and 16.9% for those aged 2-19 years, did not differ significantly from the 2007-2008 prevalence, and no difference was seen between males and females in regard to obesity prevalence, Cynthia L. Ogden, Ph.D., and her colleagues, also from the National Center for Health Statistics, CDC, reported in the same issue of JAMA.

A trend analysis over the 12-year study period did indicate, however, that the obesity prevalence among males aged 2-19 years increased significantly between 1999-2000 and 2009-2010 (OR, 1.05) per 2-year survey cycle, and that there was a significant increasing trend for non-Hispanic black males (OR, 1.10). Also, BMI increased significantly in males aged 12 through 19 years (JAMA 2012 Jan. 17 [doi:10.1001/jama.2012.40]).

NHANES data have been collected continuously since 1999, with reports released in 2-year cycles. Since no universally agreed upon definition of obesity exists for infants and toddlers up to age 2 years, high weight in this age group was defined as weight-for-recumbent length at or above the 95th percentile on the CDCs 2000 growth charts, the investigators explained.

Weight status in those aged 2 through 19 years is defined based on BMI; those at or above the sex-specific 85th percentile, but less than the 95th percentile, are considered overweight, and those at or above the sex-specific 95th percentile are considered obese. For adults, those with a BMI of 25.0 to 29.9 are considered overweight, and those with a BMI of 30.0 or higher are considered obese, with further subdivision into grades 1, 2, and 3 obesity based on BMI of 30.0 to less than 35.0, 35.0 to less than 40.0, and 40.0 or greater, respectively.

Investigators for both analyses noted that it is important to keep in mind that BMI is an "imperfect measure of body fat."

Since racial and ethnic differences in the level of body fat at specific BMIs exist, the differences in obesity prevalence by race and ethnicity in these studies may not represent actual differences in body fat, they said.

Overall, the findings in both adults and children/adolescents suggest that increases in the prevalence of obesity that have previously been observed are not continuing and have leveled off.

Although it’s difficult to predict whether these trends will continue in the same direction, the findings suggest that previous models that predict continuing increases in obesity prevalence in all age groups may be based on invalid assumptions.

None of the authors indicated having relevant conflicts of interest.

Progressive multifocal
leukoencephalopathy

Two additional cases of progressive multifocal leukoencephalopathy (PML) have been reported with the lymphoma drug brentuximab vedotin (Adcetris), according to the US Food and Drug Administration (FDA).

So the agency has added a new boxed warning to the drug’s label highlighting the risk of PML. At the time of brentuximab vedotin’s approval in August 2011, only 1 case of PML was described in the warnings and precautions section of the label.

The label change also includes a contraindication warning against the use of brentuximab vedotin with bleomycin, as the combination appears to increase the risk of pulmonary toxicity.

Diagnosing PML

The FDA says healthcare professionals should consider a possible diagnosis of PML in any patient who is receiving or has received brentuximab vedotin and who presents with new signs or symptoms of central nervous system abnormalities.

Healthcare professionals should also instruct patients to report changes in mood or usual behavior, confusion, problems thinking, loss of memory, changes in walking or talking, decreased strength or weakness on one side of the body, or changes in vision.

Evaluation of PML may include consultation with a neurologist, a brain MRI, lumbar puncture with analysis of cerebrospinal fluid by polymerase chain reaction for John Cunningham (JC) virus, and/or a brain biopsy.

Healthcare professionals should hold brentuximab vedotin dosing for any suspected case of PML and discontinue brentuximab vedotin dosing if PML is confirmed.

PML case reports

To date, 3 patients have developed PML while receiving treatment with brentuximab vedotin.

A 48-year-old man with Hodgkin lymphoma (HL) was diagnosed with PML after receiving the drug. The patient’s medical history included prior treatment with multiple chemotherapeutic agents and targeted radiation therapy.

After the third dose of brentuximab vedotin, the patient presented with left-sided weakness and slurred speech. Cerebrospinal fluid was positive for JC virus. The patient’s condition deteriorated rapidly, resulting in death within 4 weeks of symptom onset.

A 50-year-old man with HL was also diagnosed with PML after receiving brentuximab vedotin. The patient’s medical history included prior treatment with multiple chemotherapeutic agents, targeted radiation therapy, and autologous stem cell transplant.

After 8 cycles of brentuximab vedotin, this patient presented to the local emergency room with complaints of changes in speech, difficulty writing with his right hand, and right lower extremity weakness. In addition, he had poor coordination, poor balance, and left-sided sensory deficits.

Although MRI results were inconclusive and cerebrospinal fluid analyses were negative for JC virus early in the course of the neurologic work-up, an immunostain of a spinal cord lesion biopsy was positive for JC virus.

The patient’s neurological condition continues to worsen. Most recently, he lost motor function of his lower extremities and deep tendon reflexes of his legs. He also has tremulousness of his hands and hypoactive arm reflexes.

Lastly, a 38-year-old female patient with a history of stage 4 cutaneous anaplastic large cell lymphoma was diagnosed with PML after receiving brentuximab vedotin. The patient’s medical history included prior treatment with multiple chemotherapeutic agents and targeted radiation therapy.

Prior to treatment with brentuximab vedotin, a baseline neurological examination was normal. After the second dose, the patient complained of the inability to read, inability to find words to express herself, memory lapses, and slight loss of balance.

A brain MRI revealed a demyelinating process, and a brain biopsy was positive for JC virus. The patient’s treatment with brentuximab vedotin was discontinued.

Pulmonary toxicity risk

In addition to the risk of PML, research has revealed that brentuximab vedotin can confer a risk of pulmonary toxicity when combined with bleomycin.

A clinical trial compared the combination of brentuximab vedotin plus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) to combination brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (AVD) as front-line therapy for HL.

An excessive number of patients in the brentuximab vedotin plus ABVD treatment group experienced noninfectious pulmonary toxicity. The frequency of pulmonary toxicity in this group was approximately 40%, compared to a frequency of 10% to 25% previously observed with bleomycin-based regimens not containing brentuximab vedotin.

Researchers observed no pulmonary toxicity in the brentuximab vedotin plus AVD treatment group.

Progressive multifocal
leukoencephalopathy

Two additional cases of progressive multifocal leukoencephalopathy (PML) have been reported with the lymphoma drug brentuximab vedotin (Adcetris), according to the US Food and Drug Administration (FDA).

So the agency has added a new boxed warning to the drug’s label highlighting the risk of PML. At the time of brentuximab vedotin’s approval in August 2011, only 1 case of PML was described in the warnings and precautions section of the label.

The label change also includes a contraindication warning against the use of brentuximab vedotin with bleomycin, as the combination appears to increase the risk of pulmonary toxicity.

Diagnosing PML

The FDA says healthcare professionals should consider a possible diagnosis of PML in any patient who is receiving or has received brentuximab vedotin and who presents with new signs or symptoms of central nervous system abnormalities.

Healthcare professionals should also instruct patients to report changes in mood or usual behavior, confusion, problems thinking, loss of memory, changes in walking or talking, decreased strength or weakness on one side of the body, or changes in vision.

Evaluation of PML may include consultation with a neurologist, a brain MRI, lumbar puncture with analysis of cerebrospinal fluid by polymerase chain reaction for John Cunningham (JC) virus, and/or a brain biopsy.

Healthcare professionals should hold brentuximab vedotin dosing for any suspected case of PML and discontinue brentuximab vedotin dosing if PML is confirmed.

PML case reports

To date, 3 patients have developed PML while receiving treatment with brentuximab vedotin.

A 48-year-old man with Hodgkin lymphoma (HL) was diagnosed with PML after receiving the drug. The patient’s medical history included prior treatment with multiple chemotherapeutic agents and targeted radiation therapy.

After the third dose of brentuximab vedotin, the patient presented with left-sided weakness and slurred speech. Cerebrospinal fluid was positive for JC virus. The patient’s condition deteriorated rapidly, resulting in death within 4 weeks of symptom onset.

A 50-year-old man with HL was also diagnosed with PML after receiving brentuximab vedotin. The patient’s medical history included prior treatment with multiple chemotherapeutic agents, targeted radiation therapy, and autologous stem cell transplant.

After 8 cycles of brentuximab vedotin, this patient presented to the local emergency room with complaints of changes in speech, difficulty writing with his right hand, and right lower extremity weakness. In addition, he had poor coordination, poor balance, and left-sided sensory deficits.

Although MRI results were inconclusive and cerebrospinal fluid analyses were negative for JC virus early in the course of the neurologic work-up, an immunostain of a spinal cord lesion biopsy was positive for JC virus.

The patient’s neurological condition continues to worsen. Most recently, he lost motor function of his lower extremities and deep tendon reflexes of his legs. He also has tremulousness of his hands and hypoactive arm reflexes.

Lastly, a 38-year-old female patient with a history of stage 4 cutaneous anaplastic large cell lymphoma was diagnosed with PML after receiving brentuximab vedotin. The patient’s medical history included prior treatment with multiple chemotherapeutic agents and targeted radiation therapy.

Prior to treatment with brentuximab vedotin, a baseline neurological examination was normal. After the second dose, the patient complained of the inability to read, inability to find words to express herself, memory lapses, and slight loss of balance.

A brain MRI revealed a demyelinating process, and a brain biopsy was positive for JC virus. The patient’s treatment with brentuximab vedotin was discontinued.

Pulmonary toxicity risk

In addition to the risk of PML, research has revealed that brentuximab vedotin can confer a risk of pulmonary toxicity when combined with bleomycin.

A clinical trial compared the combination of brentuximab vedotin plus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) to combination brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (AVD) as front-line therapy for HL.

An excessive number of patients in the brentuximab vedotin plus ABVD treatment group experienced noninfectious pulmonary toxicity. The frequency of pulmonary toxicity in this group was approximately 40%, compared to a frequency of 10% to 25% previously observed with bleomycin-based regimens not containing brentuximab vedotin.

Researchers observed no pulmonary toxicity in the brentuximab vedotin plus AVD treatment group.

Progressive multifocal
leukoencephalopathy

Two additional cases of progressive multifocal leukoencephalopathy (PML) have been reported with the lymphoma drug brentuximab vedotin (Adcetris), according to the US Food and Drug Administration (FDA).

So the agency has added a new boxed warning to the drug’s label highlighting the risk of PML. At the time of brentuximab vedotin’s approval in August 2011, only 1 case of PML was described in the warnings and precautions section of the label.

The label change also includes a contraindication warning against the use of brentuximab vedotin with bleomycin, as the combination appears to increase the risk of pulmonary toxicity.

Diagnosing PML

The FDA says healthcare professionals should consider a possible diagnosis of PML in any patient who is receiving or has received brentuximab vedotin and who presents with new signs or symptoms of central nervous system abnormalities.

Healthcare professionals should also instruct patients to report changes in mood or usual behavior, confusion, problems thinking, loss of memory, changes in walking or talking, decreased strength or weakness on one side of the body, or changes in vision.

Evaluation of PML may include consultation with a neurologist, a brain MRI, lumbar puncture with analysis of cerebrospinal fluid by polymerase chain reaction for John Cunningham (JC) virus, and/or a brain biopsy.

Healthcare professionals should hold brentuximab vedotin dosing for any suspected case of PML and discontinue brentuximab vedotin dosing if PML is confirmed.

PML case reports

To date, 3 patients have developed PML while receiving treatment with brentuximab vedotin.

A 48-year-old man with Hodgkin lymphoma (HL) was diagnosed with PML after receiving the drug. The patient’s medical history included prior treatment with multiple chemotherapeutic agents and targeted radiation therapy.

After the third dose of brentuximab vedotin, the patient presented with left-sided weakness and slurred speech. Cerebrospinal fluid was positive for JC virus. The patient’s condition deteriorated rapidly, resulting in death within 4 weeks of symptom onset.

A 50-year-old man with HL was also diagnosed with PML after receiving brentuximab vedotin. The patient’s medical history included prior treatment with multiple chemotherapeutic agents, targeted radiation therapy, and autologous stem cell transplant.

After 8 cycles of brentuximab vedotin, this patient presented to the local emergency room with complaints of changes in speech, difficulty writing with his right hand, and right lower extremity weakness. In addition, he had poor coordination, poor balance, and left-sided sensory deficits.

Although MRI results were inconclusive and cerebrospinal fluid analyses were negative for JC virus early in the course of the neurologic work-up, an immunostain of a spinal cord lesion biopsy was positive for JC virus.

The patient’s neurological condition continues to worsen. Most recently, he lost motor function of his lower extremities and deep tendon reflexes of his legs. He also has tremulousness of his hands and hypoactive arm reflexes.

Lastly, a 38-year-old female patient with a history of stage 4 cutaneous anaplastic large cell lymphoma was diagnosed with PML after receiving brentuximab vedotin. The patient’s medical history included prior treatment with multiple chemotherapeutic agents and targeted radiation therapy.

Prior to treatment with brentuximab vedotin, a baseline neurological examination was normal. After the second dose, the patient complained of the inability to read, inability to find words to express herself, memory lapses, and slight loss of balance.

A brain MRI revealed a demyelinating process, and a brain biopsy was positive for JC virus. The patient’s treatment with brentuximab vedotin was discontinued.

Pulmonary toxicity risk

In addition to the risk of PML, research has revealed that brentuximab vedotin can confer a risk of pulmonary toxicity when combined with bleomycin.

A clinical trial compared the combination of brentuximab vedotin plus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) to combination brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (AVD) as front-line therapy for HL.

An excessive number of patients in the brentuximab vedotin plus ABVD treatment group experienced noninfectious pulmonary toxicity. The frequency of pulmonary toxicity in this group was approximately 40%, compared to a frequency of 10% to 25% previously observed with bleomycin-based regimens not containing brentuximab vedotin.

Researchers observed no pulmonary toxicity in the brentuximab vedotin plus AVD treatment group.

Hospitalizations for drowning dropped 51% between 1993 and 2008, according to the results of a study based on data from the Nationwide Inpatient Sample.

The number of hospitalizations fell from an estimated 3,623 in 1993 to 1,781 in 2008. During the same period, the estimated annual incidence rate of pediatric hospitalizations associated with drowning declined 57% – from 4.9 to 2.1 per 100,000, according to findings published online Jan. 16 in Pediatrics (2012;129:1-7).

"Our study provides national estimates of pediatric drowning hospitalizations that can be used as benchmarks to inform drowning prevention efforts and to help target interventions to high-risk areas. Given the significant burden of drowning in both real and human costs, additional monitoring of pediatric drowning is needed," wrote Stephen M. Bowman, Ph.D., of the center for injury research and policy at Johns Hopkins University in Baltimore, and his coinvestigators.

"This is an important finding that provides some evidence of a true decrease in drowning incidents."

The researchers used administrative discharge data from the 1993 to 2008 Nationwide Inpatient Sample (NIS). The NIS is created from state inpatient databases provided by public/private statewide data organizations from participating states. The NIS is the largest, longitudinal, all-payer inpatient care database in the United States, with an average of 8 million hospitalizations from approximately 1,000 hospitals each year, the researchers noted. The NIS approximates a 20% stratified random sample of all short-term U.S. community hospitals.

Eligibility for this study was limited to children and adolescents who were aged 0-19 years at admission and who were hospitalized with a primary or secondary ICD-9-CM diagnosis code for drowning injury. Patients who died while hospitalized were included.

The circumstances of drowning were determined based on the external cause of injury code when possible. The circumstances of drowning injury were categorized into five groups: recreational swimming and diving, drowning in bathtubs, other drowning activities, all other codes, and missing. For the incidence rate calculations, the investigators used U.S. Census estimates for the national civilian population at midyears during this time interval. External cause of injury codes were missing for up to 55% of hospitalizations before 1997. For this reason, the investigators compared 2-year aggregate data for the years 1998-1999 and 2007-2008 to evaluate changes in drowning mechanism and intent over time.

Drowning characteristics typically differ by age and sex. Young children (less than 4 years of age) have the greatest mortality rate from drowning and are more likely to drown while bathing or falling into water, the authors noted. Older children are more likely to drown while swimming in open water. In addition, males are four to six times more likely than females to experience a drowning injury, because of factors such as overestimation of swimming ability and greater use of alcohol by adolescent males, Dr. Bowman and his associates said.

The hospitalization rates declined significantly for all ages and for both sexes. However, the rate for males remained greater at each point in time. The total annual hospital days also declined from an estimated 14,570 days in 1993 to approximately 6,295 days in 2008. However no trend in mean hospital length of stay was observed.

"Consistent with decreases in pediatric drowning mortality, we observed a significant decline in the rate of pediatric drowning hospitalizations, primarily because of decreases in the South and West. This is an important finding that provides some evidence of a true decrease in drowning incidents, rather than a possible shift from fatal out-of-hospital drowning to nonfatal in-hospital cases," Dr. Bowman and his associates wrote. Hospitalization rates decreased significantly across all geographic regions of the United States, although the greatest decline in drowning hospitalization rates occurred in the South. The overall drowning rate fell from 7.5 hospitalizations per 100,000 in 1993-1994 to 3.5 per 100,000 in 2007-2008 in this region.

"Between 1998-1999 and 2007-2008, we observed a significant change in drowning hospitalization rates for selected ages and mechanisms," they wrote. Overall, there was a significant decline (40%) in bathtub-related drowning hospitalizations in children aged 0-4 years. Drowning hospitalizations due to swimming and diving decreased by nearly half in older children aged 10-14 years.

"Reductions in bathtub drowning hospitalizations among the youngest children may reflect a response to targeted injury prevention efforts that have been aimed at parents and caregivers of young children, encouraging increased vigilance in supervision.

"Interestingly, we did observe a decrease in the rate of in-hospital deaths over the 14-year period, although the in-hospital case fatality did not change significantly," the researchers noted. In-hospital mortality declined 42% from an estimated 359 deaths in 1993 to 207 deaths in 2008. "Although improvements in treatment might be having an impact on survival, it is not clear from these data what level of neurologic functioning survivors may have. An alternate explanation is that better decision making in the prehospital period may be resulting in more pronouncement of death in the field for unsurvivable cases."

The study was funded by the National Institutes of Health. Dr. Bowman and his associates reported that they have no relevant financial disclosures.

Hospitalizations for drowning dropped 51% between 1993 and 2008, according to the results of a study based on data from the Nationwide Inpatient Sample.

The number of hospitalizations fell from an estimated 3,623 in 1993 to 1,781 in 2008. During the same period, the estimated annual incidence rate of pediatric hospitalizations associated with drowning declined 57% – from 4.9 to 2.1 per 100,000, according to findings published online Jan. 16 in Pediatrics (2012;129:1-7).

"Our study provides national estimates of pediatric drowning hospitalizations that can be used as benchmarks to inform drowning prevention efforts and to help target interventions to high-risk areas. Given the significant burden of drowning in both real and human costs, additional monitoring of pediatric drowning is needed," wrote Stephen M. Bowman, Ph.D., of the center for injury research and policy at Johns Hopkins University in Baltimore, and his coinvestigators.

"This is an important finding that provides some evidence of a true decrease in drowning incidents."

The researchers used administrative discharge data from the 1993 to 2008 Nationwide Inpatient Sample (NIS). The NIS is created from state inpatient databases provided by public/private statewide data organizations from participating states. The NIS is the largest, longitudinal, all-payer inpatient care database in the United States, with an average of 8 million hospitalizations from approximately 1,000 hospitals each year, the researchers noted. The NIS approximates a 20% stratified random sample of all short-term U.S. community hospitals.

Eligibility for this study was limited to children and adolescents who were aged 0-19 years at admission and who were hospitalized with a primary or secondary ICD-9-CM diagnosis code for drowning injury. Patients who died while hospitalized were included.

The circumstances of drowning were determined based on the external cause of injury code when possible. The circumstances of drowning injury were categorized into five groups: recreational swimming and diving, drowning in bathtubs, other drowning activities, all other codes, and missing. For the incidence rate calculations, the investigators used U.S. Census estimates for the national civilian population at midyears during this time interval. External cause of injury codes were missing for up to 55% of hospitalizations before 1997. For this reason, the investigators compared 2-year aggregate data for the years 1998-1999 and 2007-2008 to evaluate changes in drowning mechanism and intent over time.

Drowning characteristics typically differ by age and sex. Young children (less than 4 years of age) have the greatest mortality rate from drowning and are more likely to drown while bathing or falling into water, the authors noted. Older children are more likely to drown while swimming in open water. In addition, males are four to six times more likely than females to experience a drowning injury, because of factors such as overestimation of swimming ability and greater use of alcohol by adolescent males, Dr. Bowman and his associates said.

The hospitalization rates declined significantly for all ages and for both sexes. However, the rate for males remained greater at each point in time. The total annual hospital days also declined from an estimated 14,570 days in 1993 to approximately 6,295 days in 2008. However no trend in mean hospital length of stay was observed.

"Consistent with decreases in pediatric drowning mortality, we observed a significant decline in the rate of pediatric drowning hospitalizations, primarily because of decreases in the South and West. This is an important finding that provides some evidence of a true decrease in drowning incidents, rather than a possible shift from fatal out-of-hospital drowning to nonfatal in-hospital cases," Dr. Bowman and his associates wrote. Hospitalization rates decreased significantly across all geographic regions of the United States, although the greatest decline in drowning hospitalization rates occurred in the South. The overall drowning rate fell from 7.5 hospitalizations per 100,000 in 1993-1994 to 3.5 per 100,000 in 2007-2008 in this region.

"Between 1998-1999 and 2007-2008, we observed a significant change in drowning hospitalization rates for selected ages and mechanisms," they wrote. Overall, there was a significant decline (40%) in bathtub-related drowning hospitalizations in children aged 0-4 years. Drowning hospitalizations due to swimming and diving decreased by nearly half in older children aged 10-14 years.

"Reductions in bathtub drowning hospitalizations among the youngest children may reflect a response to targeted injury prevention efforts that have been aimed at parents and caregivers of young children, encouraging increased vigilance in supervision.

"Interestingly, we did observe a decrease in the rate of in-hospital deaths over the 14-year period, although the in-hospital case fatality did not change significantly," the researchers noted. In-hospital mortality declined 42% from an estimated 359 deaths in 1993 to 207 deaths in 2008. "Although improvements in treatment might be having an impact on survival, it is not clear from these data what level of neurologic functioning survivors may have. An alternate explanation is that better decision making in the prehospital period may be resulting in more pronouncement of death in the field for unsurvivable cases."

The study was funded by the National Institutes of Health. Dr. Bowman and his associates reported that they have no relevant financial disclosures.

Hospitalizations for drowning dropped 51% between 1993 and 2008, according to the results of a study based on data from the Nationwide Inpatient Sample.

The number of hospitalizations fell from an estimated 3,623 in 1993 to 1,781 in 2008. During the same period, the estimated annual incidence rate of pediatric hospitalizations associated with drowning declined 57% – from 4.9 to 2.1 per 100,000, according to findings published online Jan. 16 in Pediatrics (2012;129:1-7).

"Our study provides national estimates of pediatric drowning hospitalizations that can be used as benchmarks to inform drowning prevention efforts and to help target interventions to high-risk areas. Given the significant burden of drowning in both real and human costs, additional monitoring of pediatric drowning is needed," wrote Stephen M. Bowman, Ph.D., of the center for injury research and policy at Johns Hopkins University in Baltimore, and his coinvestigators.

"This is an important finding that provides some evidence of a true decrease in drowning incidents."

The researchers used administrative discharge data from the 1993 to 2008 Nationwide Inpatient Sample (NIS). The NIS is created from state inpatient databases provided by public/private statewide data organizations from participating states. The NIS is the largest, longitudinal, all-payer inpatient care database in the United States, with an average of 8 million hospitalizations from approximately 1,000 hospitals each year, the researchers noted. The NIS approximates a 20% stratified random sample of all short-term U.S. community hospitals.

Eligibility for this study was limited to children and adolescents who were aged 0-19 years at admission and who were hospitalized with a primary or secondary ICD-9-CM diagnosis code for drowning injury. Patients who died while hospitalized were included.

The circumstances of drowning were determined based on the external cause of injury code when possible. The circumstances of drowning injury were categorized into five groups: recreational swimming and diving, drowning in bathtubs, other drowning activities, all other codes, and missing. For the incidence rate calculations, the investigators used U.S. Census estimates for the national civilian population at midyears during this time interval. External cause of injury codes were missing for up to 55% of hospitalizations before 1997. For this reason, the investigators compared 2-year aggregate data for the years 1998-1999 and 2007-2008 to evaluate changes in drowning mechanism and intent over time.

Drowning characteristics typically differ by age and sex. Young children (less than 4 years of age) have the greatest mortality rate from drowning and are more likely to drown while bathing or falling into water, the authors noted. Older children are more likely to drown while swimming in open water. In addition, males are four to six times more likely than females to experience a drowning injury, because of factors such as overestimation of swimming ability and greater use of alcohol by adolescent males, Dr. Bowman and his associates said.

The hospitalization rates declined significantly for all ages and for both sexes. However, the rate for males remained greater at each point in time. The total annual hospital days also declined from an estimated 14,570 days in 1993 to approximately 6,295 days in 2008. However no trend in mean hospital length of stay was observed.

"Consistent with decreases in pediatric drowning mortality, we observed a significant decline in the rate of pediatric drowning hospitalizations, primarily because of decreases in the South and West. This is an important finding that provides some evidence of a true decrease in drowning incidents, rather than a possible shift from fatal out-of-hospital drowning to nonfatal in-hospital cases," Dr. Bowman and his associates wrote. Hospitalization rates decreased significantly across all geographic regions of the United States, although the greatest decline in drowning hospitalization rates occurred in the South. The overall drowning rate fell from 7.5 hospitalizations per 100,000 in 1993-1994 to 3.5 per 100,000 in 2007-2008 in this region.

"Between 1998-1999 and 2007-2008, we observed a significant change in drowning hospitalization rates for selected ages and mechanisms," they wrote. Overall, there was a significant decline (40%) in bathtub-related drowning hospitalizations in children aged 0-4 years. Drowning hospitalizations due to swimming and diving decreased by nearly half in older children aged 10-14 years.

"Reductions in bathtub drowning hospitalizations among the youngest children may reflect a response to targeted injury prevention efforts that have been aimed at parents and caregivers of young children, encouraging increased vigilance in supervision.

"Interestingly, we did observe a decrease in the rate of in-hospital deaths over the 14-year period, although the in-hospital case fatality did not change significantly," the researchers noted. In-hospital mortality declined 42% from an estimated 359 deaths in 1993 to 207 deaths in 2008. "Although improvements in treatment might be having an impact on survival, it is not clear from these data what level of neurologic functioning survivors may have. An alternate explanation is that better decision making in the prehospital period may be resulting in more pronouncement of death in the field for unsurvivable cases."

The study was funded by the National Institutes of Health. Dr. Bowman and his associates reported that they have no relevant financial disclosures.

Background Little is known about the impact of myelodysplastic syndromes (MDS) on the quality of life (QoL) of those living with the disease. 

Objectives To explore the impact of MDS on the quality of life of those living with the disease.

Methods Seventy patients with MDS participated in five focus groups conducted throughout the United States. Transcripts from recordings of focus group sessions were coded and emerging themes identified using thematic analysis.

Results Findings revealed a multifaceted description of how MDS affects QoL. MDS was found to cause a substantial and sustained decrease in ability to function. QoL was adversely affected by work expended on managing the disease. The emotional impact was often viewed as more problematic than the physical impact; emotional reactions included shock, anger, depression, and anxiety. In contrast, spiritual well-being was often enhanced, with a renewed appreciation for life, relationships, and faith.

Limitations The method of subject recruitment may have limited participation to individuals who are more proactive in obtaining information about their illness. The focus groups convened only once, thus purposive sampling and repeated assessments were not possible.

Conclusions MDS has a substantial, often negative impact on patients' lives and clinicians should be cognizant of this impact. Attention must be directed at providing more comprehensive support for the patient throughout the illness trajectory.

Click on the PDF icon at the top of this introduction to read the full article.

Background Little is known about the impact of myelodysplastic syndromes (MDS) on the quality of life (QoL) of those living with the disease. 

Objectives To explore the impact of MDS on the quality of life of those living with the disease.

Methods Seventy patients with MDS participated in five focus groups conducted throughout the United States. Transcripts from recordings of focus group sessions were coded and emerging themes identified using thematic analysis.

Results Findings revealed a multifaceted description of how MDS affects QoL. MDS was found to cause a substantial and sustained decrease in ability to function. QoL was adversely affected by work expended on managing the disease. The emotional impact was often viewed as more problematic than the physical impact; emotional reactions included shock, anger, depression, and anxiety. In contrast, spiritual well-being was often enhanced, with a renewed appreciation for life, relationships, and faith.

Limitations The method of subject recruitment may have limited participation to individuals who are more proactive in obtaining information about their illness. The focus groups convened only once, thus purposive sampling and repeated assessments were not possible.

Conclusions MDS has a substantial, often negative impact on patients' lives and clinicians should be cognizant of this impact. Attention must be directed at providing more comprehensive support for the patient throughout the illness trajectory.

Click on the PDF icon at the top of this introduction to read the full article.

Background Little is known about the impact of myelodysplastic syndromes (MDS) on the quality of life (QoL) of those living with the disease. 

Objectives To explore the impact of MDS on the quality of life of those living with the disease.

Methods Seventy patients with MDS participated in five focus groups conducted throughout the United States. Transcripts from recordings of focus group sessions were coded and emerging themes identified using thematic analysis.

Results Findings revealed a multifaceted description of how MDS affects QoL. MDS was found to cause a substantial and sustained decrease in ability to function. QoL was adversely affected by work expended on managing the disease. The emotional impact was often viewed as more problematic than the physical impact; emotional reactions included shock, anger, depression, and anxiety. In contrast, spiritual well-being was often enhanced, with a renewed appreciation for life, relationships, and faith.

Limitations The method of subject recruitment may have limited participation to individuals who are more proactive in obtaining information about their illness. The focus groups convened only once, thus purposive sampling and repeated assessments were not possible.

Conclusions MDS has a substantial, often negative impact on patients' lives and clinicians should be cognizant of this impact. Attention must be directed at providing more comprehensive support for the patient throughout the illness trajectory.

Click on the PDF icon at the top of this introduction to read the full article.

Determinants of Physical Activity in Palliative Cancer Patients: An Application of the Theory of Planned Behavior

• Sonya S. Lowe, MD, MSc
  
  ^,

  

  ,
• Sharon M. Watanabe, MD,
• Vickie E. Baracos, PhD,
• Kerry S. Courneya, PhD

• Department of Symptom Control and Palliative Care, The Division of Palliative Care Medicine, Department of Oncology, and the Faculty of Physical Education and Recreation, University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada

• Received 23 March 2011. Accepted 29 July 2011. Available online 12 October 2011.

• http://dx.doi.org/10.1016/j.suponc.2011.07.005, How to Cite or Link Using DOI

• Permissions & Reprints

Determinants of Physical Activity in Palliative Cancer Patients: An Application of the Theory of Planned Behavior

• Sonya S. Lowe, MD, MSc
  
  ^,

  

  ,
• Sharon M. Watanabe, MD,
• Vickie E. Baracos, PhD,
• Kerry S. Courneya, PhD

• Department of Symptom Control and Palliative Care, The Division of Palliative Care Medicine, Department of Oncology, and the Faculty of Physical Education and Recreation, University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada

• Received 23 March 2011. Accepted 29 July 2011. Available online 12 October 2011.

• http://dx.doi.org/10.1016/j.suponc.2011.07.005, How to Cite or Link Using DOI

• Permissions & Reprints

Determinants of Physical Activity in Palliative Cancer Patients: An Application of the Theory of Planned Behavior

• Sonya S. Lowe, MD, MSc
  
  ^,

  

  ,
• Sharon M. Watanabe, MD,
• Vickie E. Baracos, PhD,
• Kerry S. Courneya, PhD

• Department of Symptom Control and Palliative Care, The Division of Palliative Care Medicine, Department of Oncology, and the Faculty of Physical Education and Recreation, University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada

• Received 23 March 2011. Accepted 29 July 2011. Available online 12 October 2011.

• http://dx.doi.org/10.1016/j.suponc.2011.07.005, How to Cite or Link Using DOI

• Permissions & Reprints

Managing Side Effects of Tyrosine Kinase Inhibitor Therapy to Optimize Adherence in Patients with Chronic Myeloid Leukemia: The Role of the Midlevel Practitioner

• Megan Cornelison, MS, PA-C ,
• Elias J. Jabbour, MD ,
• Mary Alma Welch, MS, PA-C^,

  

• Received 2 May 2011. Accepted 5 August 2011. Available online 11 January 2012.

• http://dx.doi.org/10.1016/j.suponc.2011.08.001

• Permissions & Reprints

  ABSTRACT

  In the last decade, the development of imatinib, a tyrosine kinase inhibitor, has brought about unprecedented change in the way newly diagnosed, chronic-phase chronic myeloid leukemia patients are treated. Two next-generation tyrosine kinase inhibitors, nilotinib and dasatinib, were initially indicated for imatinib-resistant or imatinib-intolerant chronic myeloid leukemia patients and recently received approval from the Food and Drug Administration for treatment of newly diagnosed, chronic-phase chronic myeloid leukemia patients. In comparison with the previous standards of care, benefits with these three tyrosine kinase inhibitors have included more rapid response rates, increased survival, and fewer side effects. The improved long-term outcomes have altered the approach to management of chronic myeloid leukemia from a progressive fatal disease with a poor prognosis to a chronic condition similar to diabetes or hypertension. Prolonged survival increases the need for patient education, support, monitoring, and assistance with adverse event management. Even low-grade side effects can adversely affect patients' quality of life and, therefore, require prompt attention to prevent long-term complications or suboptimal outcomes. New evidence has indicated that patient adherence to tyrosine kinase inhibitor therapy is essential to successful treatment. Midlevel practitioners can help to optimize outcomes by educating patients regarding the importance of adherence, performing regular monitoring, helping patients to understand their test results, and aggressively managing treatment-related side effects.

Managing Side Effects of Tyrosine Kinase Inhibitor Therapy to Optimize Adherence in Patients with Chronic Myeloid Leukemia: The Role of the Midlevel Practitioner

• Megan Cornelison, MS, PA-C ,
• Elias J. Jabbour, MD ,
• Mary Alma Welch, MS, PA-C^,

  

• Received 2 May 2011. Accepted 5 August 2011. Available online 11 January 2012.

• http://dx.doi.org/10.1016/j.suponc.2011.08.001

• Permissions & Reprints

  ABSTRACT

  In the last decade, the development of imatinib, a tyrosine kinase inhibitor, has brought about unprecedented change in the way newly diagnosed, chronic-phase chronic myeloid leukemia patients are treated. Two next-generation tyrosine kinase inhibitors, nilotinib and dasatinib, were initially indicated for imatinib-resistant or imatinib-intolerant chronic myeloid leukemia patients and recently received approval from the Food and Drug Administration for treatment of newly diagnosed, chronic-phase chronic myeloid leukemia patients. In comparison with the previous standards of care, benefits with these three tyrosine kinase inhibitors have included more rapid response rates, increased survival, and fewer side effects. The improved long-term outcomes have altered the approach to management of chronic myeloid leukemia from a progressive fatal disease with a poor prognosis to a chronic condition similar to diabetes or hypertension. Prolonged survival increases the need for patient education, support, monitoring, and assistance with adverse event management. Even low-grade side effects can adversely affect patients' quality of life and, therefore, require prompt attention to prevent long-term complications or suboptimal outcomes. New evidence has indicated that patient adherence to tyrosine kinase inhibitor therapy is essential to successful treatment. Midlevel practitioners can help to optimize outcomes by educating patients regarding the importance of adherence, performing regular monitoring, helping patients to understand their test results, and aggressively managing treatment-related side effects.

Managing Side Effects of Tyrosine Kinase Inhibitor Therapy to Optimize Adherence in Patients with Chronic Myeloid Leukemia: The Role of the Midlevel Practitioner

• Megan Cornelison, MS, PA-C ,
• Elias J. Jabbour, MD ,
• Mary Alma Welch, MS, PA-C^,

  

• Received 2 May 2011. Accepted 5 August 2011. Available online 11 January 2012.

• http://dx.doi.org/10.1016/j.suponc.2011.08.001

• Permissions & Reprints

  ABSTRACT

  In the last decade, the development of imatinib, a tyrosine kinase inhibitor, has brought about unprecedented change in the way newly diagnosed, chronic-phase chronic myeloid leukemia patients are treated. Two next-generation tyrosine kinase inhibitors, nilotinib and dasatinib, were initially indicated for imatinib-resistant or imatinib-intolerant chronic myeloid leukemia patients and recently received approval from the Food and Drug Administration for treatment of newly diagnosed, chronic-phase chronic myeloid leukemia patients. In comparison with the previous standards of care, benefits with these three tyrosine kinase inhibitors have included more rapid response rates, increased survival, and fewer side effects. The improved long-term outcomes have altered the approach to management of chronic myeloid leukemia from a progressive fatal disease with a poor prognosis to a chronic condition similar to diabetes or hypertension. Prolonged survival increases the need for patient education, support, monitoring, and assistance with adverse event management. Even low-grade side effects can adversely affect patients' quality of life and, therefore, require prompt attention to prevent long-term complications or suboptimal outcomes. New evidence has indicated that patient adherence to tyrosine kinase inhibitor therapy is essential to successful treatment. Midlevel practitioners can help to optimize outcomes by educating patients regarding the importance of adherence, performing regular monitoring, helping patients to understand their test results, and aggressively managing treatment-related side effects.

SAN DIEGO – Despite growing use of chemotherapy in elderly patients with acute myeloid leukemia, more than half still did not receive any chemotherapy between 1997 and 2007, according to an analysis of 6,888 cases in a large national database.

Median survival was significantly longer in patients who received chemotherapy than in those given best supportive care only, Yanni F. Yu reported at the annual meeting of the American Society of Hematology. In all, 56% of elderly acute myeloid leukemia (AML) patients did not receive chemotherapy, however, and median survival as well as chemotherapy use declined with advancing age.

"Older patient with AML generally have a poor outcome," said Ms. Yu, manager of health economics and outcomes research at Boehringer Ingelheim Pharmaceuticals. "If they are not eligible for intensive chemotherapy, the median survival is usually less than 3 months," she noted.

Previous studies in the elderly AML population showed that the percentage of chemotherapy treatment increased from 29% in 1991 to 38% in 1999, Ms. Yu said. To determine more current treatment trends in this patient population, she and her associates evaluated data from Medicare patients aged 65 years and older who had a new AML diagnosis between Jan. 1, 1997, and Dec. 31, 2007, recorded in the Surveillance, Epidemiology, and End Results (SEER) cancer registry.

The analysis was limited to fee-for-service Medicare patients who had at least 6 months of pre-AML Medicare Part A and B benefit coverage. The researchers excluded patients who had evidence of another tumor in the SEER registry before the first AML diagnosis and those who had a diagnosis of a solid tumor within 6 months pre-AML in Medicare claims.

Eligible patients were followed from initial AML diagnosis until their date of death or the end of the observation period, which was Dec. 31, 2009.

The researchers evaluated the type of care received, chemotherapy treatment patterns, and mortality and patient survival separately for AML cases diagnosed in three time frames: 1997-1999, 2000-2003, and 2004-2007. They performed multivariate logistic regression to assess predictors of receipt of chemotherapy, including patient demographics, comorbidities, and year of AML diagnosis.

A total of 6,888 patients met the study criteria. Their mean age was 78 years, 48% were women, 88% were white, and 43% received chemotherapy at any point after diagnosis. The use of chemotherapy increased slightly over time, from 40.7% in 1999-2000 to 42.3% in 2000-2003 and 46% in 2004-2007.

More than half of patients (56%) received only best supportive care post diagnosis, although the percentage decreased slightly over time. Among patients receiving best supportive care, rates of hospice care increased from 30.3% in 1997-1999 to 36.4% in 2000-2003 and 42.3% in 2004-2007.

Among patients who received chemotherapy, the use of antibiotics increased substantially over the three time periods (11.1%, 14%, and 29.6%, respectively), as did the use of antifungals (1.3%, 3.1%, and 12.4%), indicating more patients were in need of prophylaxis or treatment for chemotherapy-related infections.

Older AML patients received strikingly less chemotherapy with advancing age. For example, 66.3% of patients aged 65-74 years received chemotherapy, compared with 39.2% of those aged 75-84 years and 14.8% of those aged 85 years and older. The proportions of patients receiving antibiotics and antifungals also decreased with advancing age.

Regression analysis showed a similar association between age and chemotherapy, revealing that the strongest predictor of not receiving chemotherapy was older age, with an odds ratio of 0.12 for being aged 85 years or more and an OR of 0.42 for being aged 75-84 years.

The overall 30-day mortality rate was 20.5%, and the 60-day mortality rate was 42.8%. Median survival among all patients was 2.6 months, and it decreased with advancing age from 4.5 months to 2.4 months to 1.6 months for those aged 65-74 years, 75-84 years, and 85 years and older, respectively.

Furthermore, although nearly all patients had died during follow-up, median survival was much longer in patients receiving chemotherapy than in those receiving best supportive care only. This was true across all age groups, with 8.0 vs. 1.5 months reported in those aged 65-74 years, 5.3 vs. 1.7 months in those 75-84 years, and 3.8 vs. 1.4 months in those 85 years and older.

Ms. Yu acknowledged certain limitations of the study, including the fact that results may not be applicable to younger patients or to those covered by a managed care Medicaid plan.

In addition, "Medicare Part D information was not included since information on prescription claims was available only after 2007," she said. "Also, no information was available on the chemotherapy agents or the doses received in the inpatient or outpatient settings. Patient performance status was also unavailable."

She said that further studies are warranted "to investigate the potential benefit of chemotherapy treatment for elderly patients with AML."

The study was sponsored by Boehringer Ingelheim Pharmaceuticals. Ms. Yu disclosed that she is a full-time employee of the company.

SAN DIEGO – Despite growing use of chemotherapy in elderly patients with acute myeloid leukemia, more than half still did not receive any chemotherapy between 1997 and 2007, according to an analysis of 6,888 cases in a large national database.

Median survival was significantly longer in patients who received chemotherapy than in those given best supportive care only, Yanni F. Yu reported at the annual meeting of the American Society of Hematology. In all, 56% of elderly acute myeloid leukemia (AML) patients did not receive chemotherapy, however, and median survival as well as chemotherapy use declined with advancing age.

"Older patient with AML generally have a poor outcome," said Ms. Yu, manager of health economics and outcomes research at Boehringer Ingelheim Pharmaceuticals. "If they are not eligible for intensive chemotherapy, the median survival is usually less than 3 months," she noted.

Previous studies in the elderly AML population showed that the percentage of chemotherapy treatment increased from 29% in 1991 to 38% in 1999, Ms. Yu said. To determine more current treatment trends in this patient population, she and her associates evaluated data from Medicare patients aged 65 years and older who had a new AML diagnosis between Jan. 1, 1997, and Dec. 31, 2007, recorded in the Surveillance, Epidemiology, and End Results (SEER) cancer registry.

The analysis was limited to fee-for-service Medicare patients who had at least 6 months of pre-AML Medicare Part A and B benefit coverage. The researchers excluded patients who had evidence of another tumor in the SEER registry before the first AML diagnosis and those who had a diagnosis of a solid tumor within 6 months pre-AML in Medicare claims.

Eligible patients were followed from initial AML diagnosis until their date of death or the end of the observation period, which was Dec. 31, 2009.

The researchers evaluated the type of care received, chemotherapy treatment patterns, and mortality and patient survival separately for AML cases diagnosed in three time frames: 1997-1999, 2000-2003, and 2004-2007. They performed multivariate logistic regression to assess predictors of receipt of chemotherapy, including patient demographics, comorbidities, and year of AML diagnosis.

A total of 6,888 patients met the study criteria. Their mean age was 78 years, 48% were women, 88% were white, and 43% received chemotherapy at any point after diagnosis. The use of chemotherapy increased slightly over time, from 40.7% in 1999-2000 to 42.3% in 2000-2003 and 46% in 2004-2007.

More than half of patients (56%) received only best supportive care post diagnosis, although the percentage decreased slightly over time. Among patients receiving best supportive care, rates of hospice care increased from 30.3% in 1997-1999 to 36.4% in 2000-2003 and 42.3% in 2004-2007.

Among patients who received chemotherapy, the use of antibiotics increased substantially over the three time periods (11.1%, 14%, and 29.6%, respectively), as did the use of antifungals (1.3%, 3.1%, and 12.4%), indicating more patients were in need of prophylaxis or treatment for chemotherapy-related infections.

Older AML patients received strikingly less chemotherapy with advancing age. For example, 66.3% of patients aged 65-74 years received chemotherapy, compared with 39.2% of those aged 75-84 years and 14.8% of those aged 85 years and older. The proportions of patients receiving antibiotics and antifungals also decreased with advancing age.

Regression analysis showed a similar association between age and chemotherapy, revealing that the strongest predictor of not receiving chemotherapy was older age, with an odds ratio of 0.12 for being aged 85 years or more and an OR of 0.42 for being aged 75-84 years.

The overall 30-day mortality rate was 20.5%, and the 60-day mortality rate was 42.8%. Median survival among all patients was 2.6 months, and it decreased with advancing age from 4.5 months to 2.4 months to 1.6 months for those aged 65-74 years, 75-84 years, and 85 years and older, respectively.

Furthermore, although nearly all patients had died during follow-up, median survival was much longer in patients receiving chemotherapy than in those receiving best supportive care only. This was true across all age groups, with 8.0 vs. 1.5 months reported in those aged 65-74 years, 5.3 vs. 1.7 months in those 75-84 years, and 3.8 vs. 1.4 months in those 85 years and older.

Ms. Yu acknowledged certain limitations of the study, including the fact that results may not be applicable to younger patients or to those covered by a managed care Medicaid plan.

In addition, "Medicare Part D information was not included since information on prescription claims was available only after 2007," she said. "Also, no information was available on the chemotherapy agents or the doses received in the inpatient or outpatient settings. Patient performance status was also unavailable."

She said that further studies are warranted "to investigate the potential benefit of chemotherapy treatment for elderly patients with AML."

The study was sponsored by Boehringer Ingelheim Pharmaceuticals. Ms. Yu disclosed that she is a full-time employee of the company.

SAN DIEGO – Despite growing use of chemotherapy in elderly patients with acute myeloid leukemia, more than half still did not receive any chemotherapy between 1997 and 2007, according to an analysis of 6,888 cases in a large national database.

Median survival was significantly longer in patients who received chemotherapy than in those given best supportive care only, Yanni F. Yu reported at the annual meeting of the American Society of Hematology. In all, 56% of elderly acute myeloid leukemia (AML) patients did not receive chemotherapy, however, and median survival as well as chemotherapy use declined with advancing age.

"Older patient with AML generally have a poor outcome," said Ms. Yu, manager of health economics and outcomes research at Boehringer Ingelheim Pharmaceuticals. "If they are not eligible for intensive chemotherapy, the median survival is usually less than 3 months," she noted.

Previous studies in the elderly AML population showed that the percentage of chemotherapy treatment increased from 29% in 1991 to 38% in 1999, Ms. Yu said. To determine more current treatment trends in this patient population, she and her associates evaluated data from Medicare patients aged 65 years and older who had a new AML diagnosis between Jan. 1, 1997, and Dec. 31, 2007, recorded in the Surveillance, Epidemiology, and End Results (SEER) cancer registry.

The analysis was limited to fee-for-service Medicare patients who had at least 6 months of pre-AML Medicare Part A and B benefit coverage. The researchers excluded patients who had evidence of another tumor in the SEER registry before the first AML diagnosis and those who had a diagnosis of a solid tumor within 6 months pre-AML in Medicare claims.

Eligible patients were followed from initial AML diagnosis until their date of death or the end of the observation period, which was Dec. 31, 2009.

The researchers evaluated the type of care received, chemotherapy treatment patterns, and mortality and patient survival separately for AML cases diagnosed in three time frames: 1997-1999, 2000-2003, and 2004-2007. They performed multivariate logistic regression to assess predictors of receipt of chemotherapy, including patient demographics, comorbidities, and year of AML diagnosis.

A total of 6,888 patients met the study criteria. Their mean age was 78 years, 48% were women, 88% were white, and 43% received chemotherapy at any point after diagnosis. The use of chemotherapy increased slightly over time, from 40.7% in 1999-2000 to 42.3% in 2000-2003 and 46% in 2004-2007.

More than half of patients (56%) received only best supportive care post diagnosis, although the percentage decreased slightly over time. Among patients receiving best supportive care, rates of hospice care increased from 30.3% in 1997-1999 to 36.4% in 2000-2003 and 42.3% in 2004-2007.

Among patients who received chemotherapy, the use of antibiotics increased substantially over the three time periods (11.1%, 14%, and 29.6%, respectively), as did the use of antifungals (1.3%, 3.1%, and 12.4%), indicating more patients were in need of prophylaxis or treatment for chemotherapy-related infections.

Older AML patients received strikingly less chemotherapy with advancing age. For example, 66.3% of patients aged 65-74 years received chemotherapy, compared with 39.2% of those aged 75-84 years and 14.8% of those aged 85 years and older. The proportions of patients receiving antibiotics and antifungals also decreased with advancing age.

Regression analysis showed a similar association between age and chemotherapy, revealing that the strongest predictor of not receiving chemotherapy was older age, with an odds ratio of 0.12 for being aged 85 years or more and an OR of 0.42 for being aged 75-84 years.

The overall 30-day mortality rate was 20.5%, and the 60-day mortality rate was 42.8%. Median survival among all patients was 2.6 months, and it decreased with advancing age from 4.5 months to 2.4 months to 1.6 months for those aged 65-74 years, 75-84 years, and 85 years and older, respectively.

Furthermore, although nearly all patients had died during follow-up, median survival was much longer in patients receiving chemotherapy than in those receiving best supportive care only. This was true across all age groups, with 8.0 vs. 1.5 months reported in those aged 65-74 years, 5.3 vs. 1.7 months in those 75-84 years, and 3.8 vs. 1.4 months in those 85 years and older.

Ms. Yu acknowledged certain limitations of the study, including the fact that results may not be applicable to younger patients or to those covered by a managed care Medicaid plan.

In addition, "Medicare Part D information was not included since information on prescription claims was available only after 2007," she said. "Also, no information was available on the chemotherapy agents or the doses received in the inpatient or outpatient settings. Patient performance status was also unavailable."

She said that further studies are warranted "to investigate the potential benefit of chemotherapy treatment for elderly patients with AML."

The study was sponsored by Boehringer Ingelheim Pharmaceuticals. Ms. Yu disclosed that she is a full-time employee of the company.