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In sickle cell disease, osteomyelitis is a tough call
MONTREAL – Osteomyelitis is an especially challenging diagnosis in children with sickle cell disease (SCD) because the bone and joint signs, elevated white cell counts, and C-reactive protein levels that are commonly used to diagnose bone infection are frequently features of SCD as well.
As a result, most patients with SCD and suspected osteomyelitis are treated without a confirmation of the diagnosis.
Among 30 patients with SCD who were followed at a single center over a decade, 29 patients had elevated ESR, but only 13 patients had leukocytosis, and only 13 had elevated CRP.
“Prior studies on sickle cell disease have shown that it is very difficult to differentiate between osteoarticular infection and bone infarction. Therefore, oftentimes, this diagnosis is very difficult to make,” Dr. Weisman said at the annual meeting of the American Society of Pediatric Hematology/Oncology.
Laboratory findings for osteomyelitis in SCD are often nonspecific, including leukocytosis, elevated CRP and ESR, and blood cultures positive for Staphylococcus aureus (the predominant pathogen in children with osteomyelitis), or, in children with hemoglobinopathies, salmonella.
In children with SCD, CRP levels can vary from normal to elevated. ESR is similarly variable, as low hematocrit values can result in higher ESR values. Additionally, sickle erythrocytes can fail to aggregate, which can lead to lower ESR values.
A decade of data
The researchers set out to get a better handle on the characteristics and outcomes of osteomyelitis in patients with SCD and to see which laboratory and imaging findings might prove most useful for diagnosing osteomyelitis in this population. They reviewed data on 59 patients who were identified with indeterminate or likely osteomyelitis over a 10-year span. Of those, 30 were diagnosed and treated for osteomyelitis, and 29 were tentatively diagnosed but not treated. The latter group likely had symptoms caused by a bone infarction or vaso-occlusive crisis, Dr. Weisman said.
Among the 30 treated patients, osteomyelitis was confirmed by bone biopsy in 3, and an organism was isolated from blood or an abscess in 6. In the other 21, osteomyelitis was presumed based on clinical, laboratory, and MRI findings.
The median patient age was 12 years (range, 8 months to 18 years), 18 were male, and all but three patients have the HbSS genotype. Of the remaining patients, two had the HbSC and one the HbSF genotypes.
Infections occurred in the lower extremities in 11 patients, in the upper extremities in 10, in the pelvis or vertebrae in 2 each, and in the scapula, clavicle, hand, rib, or mandible in 1 patient each.
Just 13 of the 30 patients (43%) had lab findings of leukocytosis (more than 15,000 cells/mm2), and an equal number had elevated CRP (greater than 10 mg/L).
In contrast, 29 patients had an ESR above 20 mm/hour, and, in three of these patients, the rate was higher than 100 mm/hour.
When the researchers compared white blood cell counts and CRP levels between the treated patients and the 29 untreated controls, they found no significant differences for either measure of inflammation. In contrast, ESR was significantly higher among treated patients (P = .03).
Looking at the receiver operating characteristic curve for ESR, they found that an ESR of more than 100 mm/hour had 100% specificity for osteomyelitis in this group of patients.
Only 6 of the 30 (20%) had bacteremia. In 9 patients, nontyphoidal salmonella was isolated from cultures of either bone biopsy (3), abscess (3), or blood (6), but no possible causative organism could be isolated in the remaining 21 patients.
All patients were treated with prolonged antibiotic therapy. Surgical drainage and/or debridement were required in 6 patients. Two patients developed chronic osteomyelitis, but infection eventually resolved in all patients.
Recommendations
Dr. Weisman recommended early consultation with infectious disease experts and orthopedists; labs studies with complete blood counts, CRP, and ESR; and imaging studies with MRI when there is clinical suspicion of osteomyelitis in patients with SCD.
When an SCD patient has indeterminate findings, a blood culture can be performed. If it is positive for salmonella and the ESR is above 100 mm/hour, the patient can then go on to treatment. If the blood culture is negative and the ESR is below 100 mm hour but the suspicion of osteomyelitis remains high, a bone biopsy can be considered, they concluded.
The study was internally funded. Dr. Weisman reported no conflicts of interest to disclose.
MONTREAL – Osteomyelitis is an especially challenging diagnosis in children with sickle cell disease (SCD) because the bone and joint signs, elevated white cell counts, and C-reactive protein levels that are commonly used to diagnose bone infection are frequently features of SCD as well.
As a result, most patients with SCD and suspected osteomyelitis are treated without a confirmation of the diagnosis.
Among 30 patients with SCD who were followed at a single center over a decade, 29 patients had elevated ESR, but only 13 patients had leukocytosis, and only 13 had elevated CRP.
“Prior studies on sickle cell disease have shown that it is very difficult to differentiate between osteoarticular infection and bone infarction. Therefore, oftentimes, this diagnosis is very difficult to make,” Dr. Weisman said at the annual meeting of the American Society of Pediatric Hematology/Oncology.
Laboratory findings for osteomyelitis in SCD are often nonspecific, including leukocytosis, elevated CRP and ESR, and blood cultures positive for Staphylococcus aureus (the predominant pathogen in children with osteomyelitis), or, in children with hemoglobinopathies, salmonella.
In children with SCD, CRP levels can vary from normal to elevated. ESR is similarly variable, as low hematocrit values can result in higher ESR values. Additionally, sickle erythrocytes can fail to aggregate, which can lead to lower ESR values.
A decade of data
The researchers set out to get a better handle on the characteristics and outcomes of osteomyelitis in patients with SCD and to see which laboratory and imaging findings might prove most useful for diagnosing osteomyelitis in this population. They reviewed data on 59 patients who were identified with indeterminate or likely osteomyelitis over a 10-year span. Of those, 30 were diagnosed and treated for osteomyelitis, and 29 were tentatively diagnosed but not treated. The latter group likely had symptoms caused by a bone infarction or vaso-occlusive crisis, Dr. Weisman said.
Among the 30 treated patients, osteomyelitis was confirmed by bone biopsy in 3, and an organism was isolated from blood or an abscess in 6. In the other 21, osteomyelitis was presumed based on clinical, laboratory, and MRI findings.
The median patient age was 12 years (range, 8 months to 18 years), 18 were male, and all but three patients have the HbSS genotype. Of the remaining patients, two had the HbSC and one the HbSF genotypes.
Infections occurred in the lower extremities in 11 patients, in the upper extremities in 10, in the pelvis or vertebrae in 2 each, and in the scapula, clavicle, hand, rib, or mandible in 1 patient each.
Just 13 of the 30 patients (43%) had lab findings of leukocytosis (more than 15,000 cells/mm2), and an equal number had elevated CRP (greater than 10 mg/L).
In contrast, 29 patients had an ESR above 20 mm/hour, and, in three of these patients, the rate was higher than 100 mm/hour.
When the researchers compared white blood cell counts and CRP levels between the treated patients and the 29 untreated controls, they found no significant differences for either measure of inflammation. In contrast, ESR was significantly higher among treated patients (P = .03).
Looking at the receiver operating characteristic curve for ESR, they found that an ESR of more than 100 mm/hour had 100% specificity for osteomyelitis in this group of patients.
Only 6 of the 30 (20%) had bacteremia. In 9 patients, nontyphoidal salmonella was isolated from cultures of either bone biopsy (3), abscess (3), or blood (6), but no possible causative organism could be isolated in the remaining 21 patients.
All patients were treated with prolonged antibiotic therapy. Surgical drainage and/or debridement were required in 6 patients. Two patients developed chronic osteomyelitis, but infection eventually resolved in all patients.
Recommendations
Dr. Weisman recommended early consultation with infectious disease experts and orthopedists; labs studies with complete blood counts, CRP, and ESR; and imaging studies with MRI when there is clinical suspicion of osteomyelitis in patients with SCD.
When an SCD patient has indeterminate findings, a blood culture can be performed. If it is positive for salmonella and the ESR is above 100 mm/hour, the patient can then go on to treatment. If the blood culture is negative and the ESR is below 100 mm hour but the suspicion of osteomyelitis remains high, a bone biopsy can be considered, they concluded.
The study was internally funded. Dr. Weisman reported no conflicts of interest to disclose.
MONTREAL – Osteomyelitis is an especially challenging diagnosis in children with sickle cell disease (SCD) because the bone and joint signs, elevated white cell counts, and C-reactive protein levels that are commonly used to diagnose bone infection are frequently features of SCD as well.
As a result, most patients with SCD and suspected osteomyelitis are treated without a confirmation of the diagnosis.
Among 30 patients with SCD who were followed at a single center over a decade, 29 patients had elevated ESR, but only 13 patients had leukocytosis, and only 13 had elevated CRP.
“Prior studies on sickle cell disease have shown that it is very difficult to differentiate between osteoarticular infection and bone infarction. Therefore, oftentimes, this diagnosis is very difficult to make,” Dr. Weisman said at the annual meeting of the American Society of Pediatric Hematology/Oncology.
Laboratory findings for osteomyelitis in SCD are often nonspecific, including leukocytosis, elevated CRP and ESR, and blood cultures positive for Staphylococcus aureus (the predominant pathogen in children with osteomyelitis), or, in children with hemoglobinopathies, salmonella.
In children with SCD, CRP levels can vary from normal to elevated. ESR is similarly variable, as low hematocrit values can result in higher ESR values. Additionally, sickle erythrocytes can fail to aggregate, which can lead to lower ESR values.
A decade of data
The researchers set out to get a better handle on the characteristics and outcomes of osteomyelitis in patients with SCD and to see which laboratory and imaging findings might prove most useful for diagnosing osteomyelitis in this population. They reviewed data on 59 patients who were identified with indeterminate or likely osteomyelitis over a 10-year span. Of those, 30 were diagnosed and treated for osteomyelitis, and 29 were tentatively diagnosed but not treated. The latter group likely had symptoms caused by a bone infarction or vaso-occlusive crisis, Dr. Weisman said.
Among the 30 treated patients, osteomyelitis was confirmed by bone biopsy in 3, and an organism was isolated from blood or an abscess in 6. In the other 21, osteomyelitis was presumed based on clinical, laboratory, and MRI findings.
The median patient age was 12 years (range, 8 months to 18 years), 18 were male, and all but three patients have the HbSS genotype. Of the remaining patients, two had the HbSC and one the HbSF genotypes.
Infections occurred in the lower extremities in 11 patients, in the upper extremities in 10, in the pelvis or vertebrae in 2 each, and in the scapula, clavicle, hand, rib, or mandible in 1 patient each.
Just 13 of the 30 patients (43%) had lab findings of leukocytosis (more than 15,000 cells/mm2), and an equal number had elevated CRP (greater than 10 mg/L).
In contrast, 29 patients had an ESR above 20 mm/hour, and, in three of these patients, the rate was higher than 100 mm/hour.
When the researchers compared white blood cell counts and CRP levels between the treated patients and the 29 untreated controls, they found no significant differences for either measure of inflammation. In contrast, ESR was significantly higher among treated patients (P = .03).
Looking at the receiver operating characteristic curve for ESR, they found that an ESR of more than 100 mm/hour had 100% specificity for osteomyelitis in this group of patients.
Only 6 of the 30 (20%) had bacteremia. In 9 patients, nontyphoidal salmonella was isolated from cultures of either bone biopsy (3), abscess (3), or blood (6), but no possible causative organism could be isolated in the remaining 21 patients.
All patients were treated with prolonged antibiotic therapy. Surgical drainage and/or debridement were required in 6 patients. Two patients developed chronic osteomyelitis, but infection eventually resolved in all patients.
Recommendations
Dr. Weisman recommended early consultation with infectious disease experts and orthopedists; labs studies with complete blood counts, CRP, and ESR; and imaging studies with MRI when there is clinical suspicion of osteomyelitis in patients with SCD.
When an SCD patient has indeterminate findings, a blood culture can be performed. If it is positive for salmonella and the ESR is above 100 mm/hour, the patient can then go on to treatment. If the blood culture is negative and the ESR is below 100 mm hour but the suspicion of osteomyelitis remains high, a bone biopsy can be considered, they concluded.
The study was internally funded. Dr. Weisman reported no conflicts of interest to disclose.
Key clinical point: ESR may be a better lab marker for osteomyelitis in sickle cell disease than either WBC or CRP.
Major finding: An ESR greater than 100 mm/hr was 100% specific for osteomyelitis in this study.
Data source: A retrospective review of data on 59 patients with sickle cell disease and suspected or probable osteomyelitis.
Disclosures: The study was internally funded. Dr. Weisman reported having no conflicts of interest to disclose.
Workshop to help hospitalists with patient flow
The “flow” of patients through the hospital can sometimes resemble a 10-lane expressway at gridlock, said Christopher Kim, MD, MBA, SFHM, associate professor of internal medicine and associate medical director of quality and safety at the University of Washington Medical Center in Seattle. That is, there’s no flow at all.
Thursday at HM17, Dr. Kim and a panel of experts will lead small workshops of audience members on how to put the “go” back in the flow. The session, “Hospitalists as Leaders in Patient Flow and Hospital Throughput,” will begin at 10 a.m.
“As hospitalists, we are at the sharp end of this problem and are often asked to be key members of project teams assembled to tackle this challenge of patient flow and capacity management,” said Dr. Kim. “We look forward to an interactive session with our audience members.”
The session will address expedited discharge, the idea of the “hospitalist quarterback,” a kind of in-house controller of patient flow; facilitators of transferring to and from outside hospitals; focused efforts on reducing length of stay; establishing short-stay units to enhance patient flow; and participating in continuous process improvement teams, Dr. Kim said.
There will be several small group workshops interspersed with presentations of background content by the workshop facilitators, who represent a wide range of geographic and care settings. Dr. Kim said they have “all experienced the challenges of patient flow and throughput at their hospitals and health systems and have taken leadership roles to address these issues at their medical centers.”
“We anticipate a highly engaging session, where audience members will be divided into different teams, and each team will be tasked to identify specific interventions and challenges in managing the patient flow and capacity management initiative,” said Dr. Berger, associate medical director for inpatient capacity at the University of Washington. “Audience members will work within their own teams, guided by the workshop facilitators, and after the teams come up with their ideas on each of the topics covered in this workshop, each team will have the opportunity to present their best ideas for sharing and feedback.”
The session comes at a time when hospitals are tapping into hospitalists’ experience.
“Many hospitals across the country are challenged with high-occupancy states, creating pressures and external challenges to serve patients’ needs,” said Dr. Parekh, associate professor of internal medicine at the University of Michigan. “Hospitalists in their daily work have great familiarity with how hospitals run and where the ‘bottlenecks’ are that [block] patient throughput in their organization. Recognizing this experience and talent for enabling patient flow, many hospitals have turned to hospitalists – and in some cases, resident trainees – to lead or contribute to the hospital’s initiatives to enhance patient throughput.”
The importance of patient flow goes beyond efficiency, Dr. Kim said. Hospital staff who work during high-occupancy days feel the brunt of the burden, and this can lead to patient safety problems.
“We will address the importance of optimal communication between providers and staff, both within hospitals and with outside hospitals to ensure patient safety and staff concerns are appropriately addressed,” he said. “This is a topic that affects everyone at the medical center, and so we believe that this topic is applicable to a broad audience. We hope the participants will be able to facilitate a dialogue with a diverse group of leaders at their hospitals.”
Hospitalists as Leaders in Patient Flow and Hospital Throughput
Thursday, 10:00–11:30 a.m.
The “flow” of patients through the hospital can sometimes resemble a 10-lane expressway at gridlock, said Christopher Kim, MD, MBA, SFHM, associate professor of internal medicine and associate medical director of quality and safety at the University of Washington Medical Center in Seattle. That is, there’s no flow at all.
Thursday at HM17, Dr. Kim and a panel of experts will lead small workshops of audience members on how to put the “go” back in the flow. The session, “Hospitalists as Leaders in Patient Flow and Hospital Throughput,” will begin at 10 a.m.
“As hospitalists, we are at the sharp end of this problem and are often asked to be key members of project teams assembled to tackle this challenge of patient flow and capacity management,” said Dr. Kim. “We look forward to an interactive session with our audience members.”
The session will address expedited discharge, the idea of the “hospitalist quarterback,” a kind of in-house controller of patient flow; facilitators of transferring to and from outside hospitals; focused efforts on reducing length of stay; establishing short-stay units to enhance patient flow; and participating in continuous process improvement teams, Dr. Kim said.
There will be several small group workshops interspersed with presentations of background content by the workshop facilitators, who represent a wide range of geographic and care settings. Dr. Kim said they have “all experienced the challenges of patient flow and throughput at their hospitals and health systems and have taken leadership roles to address these issues at their medical centers.”
“We anticipate a highly engaging session, where audience members will be divided into different teams, and each team will be tasked to identify specific interventions and challenges in managing the patient flow and capacity management initiative,” said Dr. Berger, associate medical director for inpatient capacity at the University of Washington. “Audience members will work within their own teams, guided by the workshop facilitators, and after the teams come up with their ideas on each of the topics covered in this workshop, each team will have the opportunity to present their best ideas for sharing and feedback.”
The session comes at a time when hospitals are tapping into hospitalists’ experience.
“Many hospitals across the country are challenged with high-occupancy states, creating pressures and external challenges to serve patients’ needs,” said Dr. Parekh, associate professor of internal medicine at the University of Michigan. “Hospitalists in their daily work have great familiarity with how hospitals run and where the ‘bottlenecks’ are that [block] patient throughput in their organization. Recognizing this experience and talent for enabling patient flow, many hospitals have turned to hospitalists – and in some cases, resident trainees – to lead or contribute to the hospital’s initiatives to enhance patient throughput.”
The importance of patient flow goes beyond efficiency, Dr. Kim said. Hospital staff who work during high-occupancy days feel the brunt of the burden, and this can lead to patient safety problems.
“We will address the importance of optimal communication between providers and staff, both within hospitals and with outside hospitals to ensure patient safety and staff concerns are appropriately addressed,” he said. “This is a topic that affects everyone at the medical center, and so we believe that this topic is applicable to a broad audience. We hope the participants will be able to facilitate a dialogue with a diverse group of leaders at their hospitals.”
Hospitalists as Leaders in Patient Flow and Hospital Throughput
Thursday, 10:00–11:30 a.m.
The “flow” of patients through the hospital can sometimes resemble a 10-lane expressway at gridlock, said Christopher Kim, MD, MBA, SFHM, associate professor of internal medicine and associate medical director of quality and safety at the University of Washington Medical Center in Seattle. That is, there’s no flow at all.
Thursday at HM17, Dr. Kim and a panel of experts will lead small workshops of audience members on how to put the “go” back in the flow. The session, “Hospitalists as Leaders in Patient Flow and Hospital Throughput,” will begin at 10 a.m.
“As hospitalists, we are at the sharp end of this problem and are often asked to be key members of project teams assembled to tackle this challenge of patient flow and capacity management,” said Dr. Kim. “We look forward to an interactive session with our audience members.”
The session will address expedited discharge, the idea of the “hospitalist quarterback,” a kind of in-house controller of patient flow; facilitators of transferring to and from outside hospitals; focused efforts on reducing length of stay; establishing short-stay units to enhance patient flow; and participating in continuous process improvement teams, Dr. Kim said.
There will be several small group workshops interspersed with presentations of background content by the workshop facilitators, who represent a wide range of geographic and care settings. Dr. Kim said they have “all experienced the challenges of patient flow and throughput at their hospitals and health systems and have taken leadership roles to address these issues at their medical centers.”
“We anticipate a highly engaging session, where audience members will be divided into different teams, and each team will be tasked to identify specific interventions and challenges in managing the patient flow and capacity management initiative,” said Dr. Berger, associate medical director for inpatient capacity at the University of Washington. “Audience members will work within their own teams, guided by the workshop facilitators, and after the teams come up with their ideas on each of the topics covered in this workshop, each team will have the opportunity to present their best ideas for sharing and feedback.”
The session comes at a time when hospitals are tapping into hospitalists’ experience.
“Many hospitals across the country are challenged with high-occupancy states, creating pressures and external challenges to serve patients’ needs,” said Dr. Parekh, associate professor of internal medicine at the University of Michigan. “Hospitalists in their daily work have great familiarity with how hospitals run and where the ‘bottlenecks’ are that [block] patient throughput in their organization. Recognizing this experience and talent for enabling patient flow, many hospitals have turned to hospitalists – and in some cases, resident trainees – to lead or contribute to the hospital’s initiatives to enhance patient throughput.”
The importance of patient flow goes beyond efficiency, Dr. Kim said. Hospital staff who work during high-occupancy days feel the brunt of the burden, and this can lead to patient safety problems.
“We will address the importance of optimal communication between providers and staff, both within hospitals and with outside hospitals to ensure patient safety and staff concerns are appropriately addressed,” he said. “This is a topic that affects everyone at the medical center, and so we believe that this topic is applicable to a broad audience. We hope the participants will be able to facilitate a dialogue with a diverse group of leaders at their hospitals.”
Hospitalists as Leaders in Patient Flow and Hospital Throughput
Thursday, 10:00–11:30 a.m.
Systems engineering in the hospital
Systems-engineering expert James Benneyan, PhD, doesn’t want hospitalists to look at poorly working processes in their institutions and think, “I should try to tweak this process to improve it.”
Instead, he wants them to walk out of his HM17 session at 8 a.m. Thursday – appropriately titled, “Systems Engineering in the Hospital: What Is in Your Toolkit?” – thinking like engineers, which means designing a solution, analyzing how well that process works, and then optimizing it for improvements. If that means not just tweaking a process, but redesigning it from scratch, so be it.
“Systems engineering studies the performance and how to improve the performance of complex systems, particularly sociotechnical systems,” said Dr. Benneyan, who runs the Healthcare Systems Engineering Institute at Northeastern University in Boston, which encompasses four research centers. “Health care is a perfect example … systems engineering can really help to understand and improve complex processes, whether it’s patient flow, safety, on-time discharge [or] better discharge.”
Dr. Benneyan says that systems engineering is, first and foremost, a mindset. It’s an approach to problem solving that’s different, if related, to quality improvement. Both have tremendous value, but they are based on different philosophies, tools, and work styles.
For example, many hospital operating rooms measure how many days the first procedure of the day begins on time. But instead of using that as a yardstick for quality, Dr. Benneyan said a better approach would be designing a system that can adapt to situations when the first case starts late. He compared the process to a delayed flight at an airport. An airline doesn’t back up every plane’s departure when one plane is running behind. Instead, it has systems that adapt to circumstances.
“There are methods and then there are philosophies,” Dr. Benneyan said. “I don’t think people in health care realize what my field did in the airline industry. We didn’t design things that worked and clicked properly. We designed things that … react to daily events and [everything] going on and perform pretty well.”
Dr. Benneyan says that, while health care is an incredibly complex system, other fields with similar levels of technical expertise have used systems engineering much more effectively. Manufacturing, logistics, and global distribution networks are all precise industries requiring hundreds of individual processes to ensure success.
“These are really complicated processes,” he said. “The real barrier is a cultural barrier. Health care is not the most challenging environment to work in. … I think something that people in health care have to have an appreciation for is that the process of doing this work is different from doing their other work. Systems engineering is not the same as quality improvement and can achieve fundamental breakthroughs in cases where QI has not – but also tends to take more work.”
Still, Dr. Benneyan believes his field has lessons that complement quality initiatives. To wit, health care advocates – including the Institute of Medicine, the Agency for Healthcare Research and Quality, the National Institutes of Health, and the National Science Foundation – have all pushed for greater application of systems engineering in medicine with the goal of improving how well health care does its job.
While he hopes hospitalists and other HM17 attendees at his session walk away with a newfound respect for and understanding of what systems engineering can do, he doesn’t want them to think it’s too easy.
“There’s a lack of appreciation of the process of engineering and how it’s different,” he said. “It’s a big challenge, partnering clinician with engineers. … We think differently even though we’re both scientifically trained.
“I hope hospitalists take away an appreciation for how this toolkit can be useful in their world.”
Systems Engineering in the Hospital: What Is in Your Toolkit?
Thursday, 8:00–9:30 a.m.
Systems-engineering expert James Benneyan, PhD, doesn’t want hospitalists to look at poorly working processes in their institutions and think, “I should try to tweak this process to improve it.”
Instead, he wants them to walk out of his HM17 session at 8 a.m. Thursday – appropriately titled, “Systems Engineering in the Hospital: What Is in Your Toolkit?” – thinking like engineers, which means designing a solution, analyzing how well that process works, and then optimizing it for improvements. If that means not just tweaking a process, but redesigning it from scratch, so be it.
“Systems engineering studies the performance and how to improve the performance of complex systems, particularly sociotechnical systems,” said Dr. Benneyan, who runs the Healthcare Systems Engineering Institute at Northeastern University in Boston, which encompasses four research centers. “Health care is a perfect example … systems engineering can really help to understand and improve complex processes, whether it’s patient flow, safety, on-time discharge [or] better discharge.”
Dr. Benneyan says that systems engineering is, first and foremost, a mindset. It’s an approach to problem solving that’s different, if related, to quality improvement. Both have tremendous value, but they are based on different philosophies, tools, and work styles.
For example, many hospital operating rooms measure how many days the first procedure of the day begins on time. But instead of using that as a yardstick for quality, Dr. Benneyan said a better approach would be designing a system that can adapt to situations when the first case starts late. He compared the process to a delayed flight at an airport. An airline doesn’t back up every plane’s departure when one plane is running behind. Instead, it has systems that adapt to circumstances.
“There are methods and then there are philosophies,” Dr. Benneyan said. “I don’t think people in health care realize what my field did in the airline industry. We didn’t design things that worked and clicked properly. We designed things that … react to daily events and [everything] going on and perform pretty well.”
Dr. Benneyan says that, while health care is an incredibly complex system, other fields with similar levels of technical expertise have used systems engineering much more effectively. Manufacturing, logistics, and global distribution networks are all precise industries requiring hundreds of individual processes to ensure success.
“These are really complicated processes,” he said. “The real barrier is a cultural barrier. Health care is not the most challenging environment to work in. … I think something that people in health care have to have an appreciation for is that the process of doing this work is different from doing their other work. Systems engineering is not the same as quality improvement and can achieve fundamental breakthroughs in cases where QI has not – but also tends to take more work.”
Still, Dr. Benneyan believes his field has lessons that complement quality initiatives. To wit, health care advocates – including the Institute of Medicine, the Agency for Healthcare Research and Quality, the National Institutes of Health, and the National Science Foundation – have all pushed for greater application of systems engineering in medicine with the goal of improving how well health care does its job.
While he hopes hospitalists and other HM17 attendees at his session walk away with a newfound respect for and understanding of what systems engineering can do, he doesn’t want them to think it’s too easy.
“There’s a lack of appreciation of the process of engineering and how it’s different,” he said. “It’s a big challenge, partnering clinician with engineers. … We think differently even though we’re both scientifically trained.
“I hope hospitalists take away an appreciation for how this toolkit can be useful in their world.”
Systems Engineering in the Hospital: What Is in Your Toolkit?
Thursday, 8:00–9:30 a.m.
Systems-engineering expert James Benneyan, PhD, doesn’t want hospitalists to look at poorly working processes in their institutions and think, “I should try to tweak this process to improve it.”
Instead, he wants them to walk out of his HM17 session at 8 a.m. Thursday – appropriately titled, “Systems Engineering in the Hospital: What Is in Your Toolkit?” – thinking like engineers, which means designing a solution, analyzing how well that process works, and then optimizing it for improvements. If that means not just tweaking a process, but redesigning it from scratch, so be it.
“Systems engineering studies the performance and how to improve the performance of complex systems, particularly sociotechnical systems,” said Dr. Benneyan, who runs the Healthcare Systems Engineering Institute at Northeastern University in Boston, which encompasses four research centers. “Health care is a perfect example … systems engineering can really help to understand and improve complex processes, whether it’s patient flow, safety, on-time discharge [or] better discharge.”
Dr. Benneyan says that systems engineering is, first and foremost, a mindset. It’s an approach to problem solving that’s different, if related, to quality improvement. Both have tremendous value, but they are based on different philosophies, tools, and work styles.
For example, many hospital operating rooms measure how many days the first procedure of the day begins on time. But instead of using that as a yardstick for quality, Dr. Benneyan said a better approach would be designing a system that can adapt to situations when the first case starts late. He compared the process to a delayed flight at an airport. An airline doesn’t back up every plane’s departure when one plane is running behind. Instead, it has systems that adapt to circumstances.
“There are methods and then there are philosophies,” Dr. Benneyan said. “I don’t think people in health care realize what my field did in the airline industry. We didn’t design things that worked and clicked properly. We designed things that … react to daily events and [everything] going on and perform pretty well.”
Dr. Benneyan says that, while health care is an incredibly complex system, other fields with similar levels of technical expertise have used systems engineering much more effectively. Manufacturing, logistics, and global distribution networks are all precise industries requiring hundreds of individual processes to ensure success.
“These are really complicated processes,” he said. “The real barrier is a cultural barrier. Health care is not the most challenging environment to work in. … I think something that people in health care have to have an appreciation for is that the process of doing this work is different from doing their other work. Systems engineering is not the same as quality improvement and can achieve fundamental breakthroughs in cases where QI has not – but also tends to take more work.”
Still, Dr. Benneyan believes his field has lessons that complement quality initiatives. To wit, health care advocates – including the Institute of Medicine, the Agency for Healthcare Research and Quality, the National Institutes of Health, and the National Science Foundation – have all pushed for greater application of systems engineering in medicine with the goal of improving how well health care does its job.
While he hopes hospitalists and other HM17 attendees at his session walk away with a newfound respect for and understanding of what systems engineering can do, he doesn’t want them to think it’s too easy.
“There’s a lack of appreciation of the process of engineering and how it’s different,” he said. “It’s a big challenge, partnering clinician with engineers. … We think differently even though we’re both scientifically trained.
“I hope hospitalists take away an appreciation for how this toolkit can be useful in their world.”
Systems Engineering in the Hospital: What Is in Your Toolkit?
Thursday, 8:00–9:30 a.m.
Diabetes specialist to offer disease management tips
Diabetes is a persistent presence in the hospital, and hospitalists must remain up to date on the latest in disease management.
An endocrinologist will walk the audience through four major points on caring for diabetes patients in a talk to be given Thursday at HM17. The session, “Inpatient Diabetes Management for the Hospitalist,” will begin at 7:40 a.m.
Guillermo Umpierrez, MD, CDE, FACP, FACE, professor of medicine, director of the clinical research center and section of diabetes and metabolism at Emory University, Atlanta, and section head of diabetes and endocrinology at Grady Health System, also in Atlanta, said that, “in most patients, diabetes is a comorbidity that has a serious impact on the outcome of patients with cardiovascular disease or malignancies or surgery.
“Hyperglycemia in patients with or without diabetes can be 30%-40%,” he said. “There are somewhere around 8 to 10 million hospital discharges with diabetes every year in the United States.”
Dr. Umpierrez intends to discuss the following topics in his presentation:
• Intensive insulin therapy. “There is no evidence that intensive insulin therapy aiming to normalize blood glucose [leads to] improvement in outcome and could even [worsen] outcome because of the risk of hypoglycemia. This is true for patients in intensive care and the regular floor.”
• Treatment other than insulin. Guidelines say that using insulin is the only way to manage diabetic patients in the hospital, but evidence is growing that this might not be ideal in some cases, he said.
“Recent evidence in the past 5 years has shown that maybe a one-size-fits-all approach is wrong because using insulin, especially the basal-bolus insulin regimen” – with long-lasting insulin between meals and bolus insulin at mealtime – “can be an overtreatment for some patients with multiple complications and patients with mild hyperglycemia.” In many patients, the administration of a single basal insulin dose (glargine or detemir) is sufficient to achieve reasonable glucose control. In addition, patients with blood glucose less than 180 to 200 mg/dL could benefit from the use of incretin therapy with or without insulin to “at least minimize the risk of hypoglycemia.”
• Limitations for sliding-scale insulin therapy. This approach, in which mealtime bolus insulin is based on blood-sugar level before meals and which has dominated diabetes management over the past 80 years, can bring problems, according to the latest literature, Dr. Umpierrez said.
“Now we have excessive evidence, both in the ICU and non-ICU, that the use of sliding-scale insulin therapy … is associated with higher blood glucose levels [and a] higher rate of complications compared to the use of basal insulin. So, I think that physicians are becoming more aware that sliding scale is not the only way to manage patients in the hospital.”
• Insulin at discharge. The belief that all patients need to go home with insulin might be misguided, he said. “This could be an overtreatment associated with increased risk of hypoglycemia with no benefit in outcome.”
• The use of computer-guided algorithms on insulin therapy. “Are they better than the standard insulin drip protocols that we have? Not clear,” he said. Many commercial versions and institution-generated versions have been developed, but there is uncertainty about their value, he added.
“They may reduce the risk of hypoglycemia,” Dr. Umpierrez said. “We don’t have any evidence that they are better in reducing complications in the hospital. And they can be costly. So the physician has to be aware of the cost. But, it’s an option for some institutions that have very little support from hospitalists or intensivists in their hospital to adjust insulin therapy in the rapidly changing environment in critically ill patients in the ICU.”
Inpatient Diabetes Management for the Hospitalist
Thursday, 7:40–8:15 a.m.
Diabetes is a persistent presence in the hospital, and hospitalists must remain up to date on the latest in disease management.
An endocrinologist will walk the audience through four major points on caring for diabetes patients in a talk to be given Thursday at HM17. The session, “Inpatient Diabetes Management for the Hospitalist,” will begin at 7:40 a.m.
Guillermo Umpierrez, MD, CDE, FACP, FACE, professor of medicine, director of the clinical research center and section of diabetes and metabolism at Emory University, Atlanta, and section head of diabetes and endocrinology at Grady Health System, also in Atlanta, said that, “in most patients, diabetes is a comorbidity that has a serious impact on the outcome of patients with cardiovascular disease or malignancies or surgery.
“Hyperglycemia in patients with or without diabetes can be 30%-40%,” he said. “There are somewhere around 8 to 10 million hospital discharges with diabetes every year in the United States.”
Dr. Umpierrez intends to discuss the following topics in his presentation:
• Intensive insulin therapy. “There is no evidence that intensive insulin therapy aiming to normalize blood glucose [leads to] improvement in outcome and could even [worsen] outcome because of the risk of hypoglycemia. This is true for patients in intensive care and the regular floor.”
• Treatment other than insulin. Guidelines say that using insulin is the only way to manage diabetic patients in the hospital, but evidence is growing that this might not be ideal in some cases, he said.
“Recent evidence in the past 5 years has shown that maybe a one-size-fits-all approach is wrong because using insulin, especially the basal-bolus insulin regimen” – with long-lasting insulin between meals and bolus insulin at mealtime – “can be an overtreatment for some patients with multiple complications and patients with mild hyperglycemia.” In many patients, the administration of a single basal insulin dose (glargine or detemir) is sufficient to achieve reasonable glucose control. In addition, patients with blood glucose less than 180 to 200 mg/dL could benefit from the use of incretin therapy with or without insulin to “at least minimize the risk of hypoglycemia.”
• Limitations for sliding-scale insulin therapy. This approach, in which mealtime bolus insulin is based on blood-sugar level before meals and which has dominated diabetes management over the past 80 years, can bring problems, according to the latest literature, Dr. Umpierrez said.
“Now we have excessive evidence, both in the ICU and non-ICU, that the use of sliding-scale insulin therapy … is associated with higher blood glucose levels [and a] higher rate of complications compared to the use of basal insulin. So, I think that physicians are becoming more aware that sliding scale is not the only way to manage patients in the hospital.”
• Insulin at discharge. The belief that all patients need to go home with insulin might be misguided, he said. “This could be an overtreatment associated with increased risk of hypoglycemia with no benefit in outcome.”
• The use of computer-guided algorithms on insulin therapy. “Are they better than the standard insulin drip protocols that we have? Not clear,” he said. Many commercial versions and institution-generated versions have been developed, but there is uncertainty about their value, he added.
“They may reduce the risk of hypoglycemia,” Dr. Umpierrez said. “We don’t have any evidence that they are better in reducing complications in the hospital. And they can be costly. So the physician has to be aware of the cost. But, it’s an option for some institutions that have very little support from hospitalists or intensivists in their hospital to adjust insulin therapy in the rapidly changing environment in critically ill patients in the ICU.”
Inpatient Diabetes Management for the Hospitalist
Thursday, 7:40–8:15 a.m.
Diabetes is a persistent presence in the hospital, and hospitalists must remain up to date on the latest in disease management.
An endocrinologist will walk the audience through four major points on caring for diabetes patients in a talk to be given Thursday at HM17. The session, “Inpatient Diabetes Management for the Hospitalist,” will begin at 7:40 a.m.
Guillermo Umpierrez, MD, CDE, FACP, FACE, professor of medicine, director of the clinical research center and section of diabetes and metabolism at Emory University, Atlanta, and section head of diabetes and endocrinology at Grady Health System, also in Atlanta, said that, “in most patients, diabetes is a comorbidity that has a serious impact on the outcome of patients with cardiovascular disease or malignancies or surgery.
“Hyperglycemia in patients with or without diabetes can be 30%-40%,” he said. “There are somewhere around 8 to 10 million hospital discharges with diabetes every year in the United States.”
Dr. Umpierrez intends to discuss the following topics in his presentation:
• Intensive insulin therapy. “There is no evidence that intensive insulin therapy aiming to normalize blood glucose [leads to] improvement in outcome and could even [worsen] outcome because of the risk of hypoglycemia. This is true for patients in intensive care and the regular floor.”
• Treatment other than insulin. Guidelines say that using insulin is the only way to manage diabetic patients in the hospital, but evidence is growing that this might not be ideal in some cases, he said.
“Recent evidence in the past 5 years has shown that maybe a one-size-fits-all approach is wrong because using insulin, especially the basal-bolus insulin regimen” – with long-lasting insulin between meals and bolus insulin at mealtime – “can be an overtreatment for some patients with multiple complications and patients with mild hyperglycemia.” In many patients, the administration of a single basal insulin dose (glargine or detemir) is sufficient to achieve reasonable glucose control. In addition, patients with blood glucose less than 180 to 200 mg/dL could benefit from the use of incretin therapy with or without insulin to “at least minimize the risk of hypoglycemia.”
• Limitations for sliding-scale insulin therapy. This approach, in which mealtime bolus insulin is based on blood-sugar level before meals and which has dominated diabetes management over the past 80 years, can bring problems, according to the latest literature, Dr. Umpierrez said.
“Now we have excessive evidence, both in the ICU and non-ICU, that the use of sliding-scale insulin therapy … is associated with higher blood glucose levels [and a] higher rate of complications compared to the use of basal insulin. So, I think that physicians are becoming more aware that sliding scale is not the only way to manage patients in the hospital.”
• Insulin at discharge. The belief that all patients need to go home with insulin might be misguided, he said. “This could be an overtreatment associated with increased risk of hypoglycemia with no benefit in outcome.”
• The use of computer-guided algorithms on insulin therapy. “Are they better than the standard insulin drip protocols that we have? Not clear,” he said. Many commercial versions and institution-generated versions have been developed, but there is uncertainty about their value, he added.
“They may reduce the risk of hypoglycemia,” Dr. Umpierrez said. “We don’t have any evidence that they are better in reducing complications in the hospital. And they can be costly. So the physician has to be aware of the cost. But, it’s an option for some institutions that have very little support from hospitalists or intensivists in their hospital to adjust insulin therapy in the rapidly changing environment in critically ill patients in the ICU.”
Inpatient Diabetes Management for the Hospitalist
Thursday, 7:40–8:15 a.m.
Culture change necessary to weed out health care overuse
Chris Moriates, MD, assistant dean for healthcare value and associate professor of medicine at the University of Texas at Austin Dell Medical School, drew insight from writer David Foster Wallace on Tuesday afternoon as he discussed overuse in hospital care.
He cited a story by Wallace: Two young fish are swimming along when they pass an old, wise fish who says, “Mornin’, boys. How’s the water?” One of the young fish asks the other, “What the hell is water?”
For hospitalists, the culture is their water: Even though they’re swimming in it every day, it can be an abstraction that gets little attention. But the culture is what needs to be tended to in order to turn the tide of unnecessary expenses, Dr. Moriates said in his talk, “Overcoming a Culture Overrun with Overuse.”
“How we’re addressing this problem is by making guidelines, algorithms, evidence-based medicine, Choosing Wisely lists,” he said during the well-attended session in the High-Value Care track. “It’s important that we codify our practices in these ways. But it is insufficient, because we must recognize that we are all swimming in that same water.
“If we don’t change this culture, this water, we will not make any progress.”
A 2013 survey by the Society of Academic Emergency Medicine found that 97% of physicians thought that at least some of the imaging they have personally ordered is medically unnecessary. And a 2011 Annals of Internal Medicine study found that organizational culture was a key factor in distinguishing hospitals with high and low 30-day mortality rates for patients with acute myocardial infarction.
He pointed to lessons from his previous institution, the University of California San Francisco, where they launched Caring Wisely, a program meant to support front-line clinicians who want to eradicate unnecessary costs. Part of the program involves funding clinicians up to $50,000 for their projects. One such project found that feedback to surgeons about expenses, and a small financial incentive to the department to keep costs down, was associated with reduced operating room costs.
This kind of change can be done anywhere, he said. After all, culture change, he said, can start with something as small as encouraging patient interaction by asking, “What questions do you have?” rather than “Do you have any questions?”
“I don’t want you to leave and think, ‘Well, unless I work somewhere like UCSF, where they’re going to give me $50,000 to do this, or I have an amazing boss like [Dr.] Bob Wachter [the former SHM president from UCSF who coined the term “hospitalist”], there is nothing I can do about this,” Dr. Moriates said. “It turns out that, yes, that is important for changing culture, but each of us has a personal responsibility.”
Chris Moriates, MD, assistant dean for healthcare value and associate professor of medicine at the University of Texas at Austin Dell Medical School, drew insight from writer David Foster Wallace on Tuesday afternoon as he discussed overuse in hospital care.
He cited a story by Wallace: Two young fish are swimming along when they pass an old, wise fish who says, “Mornin’, boys. How’s the water?” One of the young fish asks the other, “What the hell is water?”
For hospitalists, the culture is their water: Even though they’re swimming in it every day, it can be an abstraction that gets little attention. But the culture is what needs to be tended to in order to turn the tide of unnecessary expenses, Dr. Moriates said in his talk, “Overcoming a Culture Overrun with Overuse.”
“How we’re addressing this problem is by making guidelines, algorithms, evidence-based medicine, Choosing Wisely lists,” he said during the well-attended session in the High-Value Care track. “It’s important that we codify our practices in these ways. But it is insufficient, because we must recognize that we are all swimming in that same water.
“If we don’t change this culture, this water, we will not make any progress.”
A 2013 survey by the Society of Academic Emergency Medicine found that 97% of physicians thought that at least some of the imaging they have personally ordered is medically unnecessary. And a 2011 Annals of Internal Medicine study found that organizational culture was a key factor in distinguishing hospitals with high and low 30-day mortality rates for patients with acute myocardial infarction.
He pointed to lessons from his previous institution, the University of California San Francisco, where they launched Caring Wisely, a program meant to support front-line clinicians who want to eradicate unnecessary costs. Part of the program involves funding clinicians up to $50,000 for their projects. One such project found that feedback to surgeons about expenses, and a small financial incentive to the department to keep costs down, was associated with reduced operating room costs.
This kind of change can be done anywhere, he said. After all, culture change, he said, can start with something as small as encouraging patient interaction by asking, “What questions do you have?” rather than “Do you have any questions?”
“I don’t want you to leave and think, ‘Well, unless I work somewhere like UCSF, where they’re going to give me $50,000 to do this, or I have an amazing boss like [Dr.] Bob Wachter [the former SHM president from UCSF who coined the term “hospitalist”], there is nothing I can do about this,” Dr. Moriates said. “It turns out that, yes, that is important for changing culture, but each of us has a personal responsibility.”
Chris Moriates, MD, assistant dean for healthcare value and associate professor of medicine at the University of Texas at Austin Dell Medical School, drew insight from writer David Foster Wallace on Tuesday afternoon as he discussed overuse in hospital care.
He cited a story by Wallace: Two young fish are swimming along when they pass an old, wise fish who says, “Mornin’, boys. How’s the water?” One of the young fish asks the other, “What the hell is water?”
For hospitalists, the culture is their water: Even though they’re swimming in it every day, it can be an abstraction that gets little attention. But the culture is what needs to be tended to in order to turn the tide of unnecessary expenses, Dr. Moriates said in his talk, “Overcoming a Culture Overrun with Overuse.”
“How we’re addressing this problem is by making guidelines, algorithms, evidence-based medicine, Choosing Wisely lists,” he said during the well-attended session in the High-Value Care track. “It’s important that we codify our practices in these ways. But it is insufficient, because we must recognize that we are all swimming in that same water.
“If we don’t change this culture, this water, we will not make any progress.”
A 2013 survey by the Society of Academic Emergency Medicine found that 97% of physicians thought that at least some of the imaging they have personally ordered is medically unnecessary. And a 2011 Annals of Internal Medicine study found that organizational culture was a key factor in distinguishing hospitals with high and low 30-day mortality rates for patients with acute myocardial infarction.
He pointed to lessons from his previous institution, the University of California San Francisco, where they launched Caring Wisely, a program meant to support front-line clinicians who want to eradicate unnecessary costs. Part of the program involves funding clinicians up to $50,000 for their projects. One such project found that feedback to surgeons about expenses, and a small financial incentive to the department to keep costs down, was associated with reduced operating room costs.
This kind of change can be done anywhere, he said. After all, culture change, he said, can start with something as small as encouraging patient interaction by asking, “What questions do you have?” rather than “Do you have any questions?”
“I don’t want you to leave and think, ‘Well, unless I work somewhere like UCSF, where they’re going to give me $50,000 to do this, or I have an amazing boss like [Dr.] Bob Wachter [the former SHM president from UCSF who coined the term “hospitalist”], there is nothing I can do about this,” Dr. Moriates said. “It turns out that, yes, that is important for changing culture, but each of us has a personal responsibility.”
Cord blood/placental cell combo induces rapid immune recovery
MONTREAL – A combination of placenta-derived stem cells and umbilical cord blood was associated with early engraftment and high degrees of cord blood donor chimerism in the treatment of children with both malignant and nonmalignant hematologic conditions requiring stem cell transplantation, updated results of a pilot study show.
Among 16 children treated with the combination, the probability of neutrophil engraftment was 87.5%, and all patients who had neutrophil engraftment went on to have platelet engraftment. The probability of 12-month overall survival was 81.2%, reported Allyson Flower, MD, from Boston Children’s Health Physicians in Hawthorne, N.Y. “The probability of grade II-IV acute graft vs. host disease was 12.5%, compared with 32.5% seen with unrelated cord blood in our group’s previous studies. Cellular immune reconstitution was robust,” she said at the annual meeting of the American Society of Pediatric Hematology/Oncology.
Augmenting cord blood
Although unrelated donor cord blood transplantation expands the donor pool, is rapidly available, and is associated with decreases in both severe acute graft vs. host disease (GVHD) and chronic GVHD, compared with other stem cell sources, the technique is hampered by limited cell doses, prolonged immune reconstitution time, delays in hematopoietic recovery, and a higher incidence of graft failure.
Early studies of myeloablative conditioning followed by unrelated umbilical or placental blood transplantation showed a median of 22-24 days to neutrophil engraftment (Blood 1996 88:795-802; N Engl J Med. 1996;335:157-66), Dr. Flower noted.
More recently, a multivariate analysis of patients who underwent reduced-intensity conditioning followed by hematopoietic stem cell transplant with unrelated cord blood showed that graft failure was an independent risk factor for worse overall survival (Biol Blood Marrow Transplant. 2013 Apr;19:4;552-61).
Multiple groups have shown that adding human placenta–derived stem cells (HPDSC) to cord blood transplantation can facilitate more rapid hematopoietic engraftment by increasing the number of stem cells, increasing the proportion of hematopoietic progenitor cells, and providing additional, immature CD34+/CD45– progenitor cells.
In a single-arm, nonrandomized study, the investigators enrolled 16 patients ranging in age from 0.3 to 15.7 years with inborn errors of metabolism, marrow failure syndromes, severe immunodeficiency states, or hematologic malignancies.
Malignant conditions included B-cell precursor acute lymphoblastic leukemia (B-ALL; four patients), acute myeloid leukemia (AML; two), and T-cell ALL (one) in first complete remission, and T-cell lymphoblastic lymphoma following induction failure (one). Nonmalignant conditions included adrenoleukodystrophy (two patients), amegakaryotic thrombocytopenia (one), severe combined immunodeficiency (SCID; two), dyskeratosis congenita (one), chronic granulomatous disease (one), and severe congenital neutropenia (one).
The patients first underwent either myeloablative or reduced-intensity conditioning, followed 10 days later by infusion of unrelated cord blood and HPDSCs. Prior to HPDSC infusion, patients were medicated with diphenhydramine and hydrocortisone to prevent or reduce potential sensitivity reactions. HPDSCs were infused no sooner than 4 hours after the end of the cord blood infusion.
Patients received GVHD prophylaxis with either tacrolimus or cyclosporine, plus mycophenolate mofetil.
The combination appeared to be safe, with no cases of grade 3 or 4 toxicity secondary to HPDSC infusion.
The probability of neutrophil engraftment was 87.5%, with engraftment occurring at a median of 23 days (range 13-53). As noted before, all patients who had neutrophil engraftment had platelet engraftment, which was achieved at a median of 47 days (range, 20-98). In the group’s previous studies, median time to platelet engraftment was 53 days for patients who had undergone reduced-intensity conditioning, and 118 days for patients who had undergone myeloablation.
The probability of grade 2-4 acute GVHD within 100 days was 12.5%, and there were no cases of chronic GVHD.
Respective percentages of cord blood donor chimerism at days 30, 60, 100, and 180 were 88%, 98%, 99%, and 99%.
Immune reconstitution was strong, with normalization of mean CD3+, CD19+, and CD56+ cells occurring by day 100, CD8+ cells by day 180, and CD4+ cells by day 270.
There were three patient deaths: one from adenoviremia in a patient with B-ALL and CNS relapse, who had neutrophil engraftment at day 21; one in a patient with SCID, from adenoviremia and multiple system organ failure, who did not have engraftment before death; and one in a patient with severe congenital neutrophilia, who also did not have neutrophil engraftment.
None of the eight patients with malignant disease have experienced relapse to date, Dr. Flower noted.
The study was funded by a grant from Celgene Cellular Therapeutics. Dr. Flower reported having no conflicts of interest.
MONTREAL – A combination of placenta-derived stem cells and umbilical cord blood was associated with early engraftment and high degrees of cord blood donor chimerism in the treatment of children with both malignant and nonmalignant hematologic conditions requiring stem cell transplantation, updated results of a pilot study show.
Among 16 children treated with the combination, the probability of neutrophil engraftment was 87.5%, and all patients who had neutrophil engraftment went on to have platelet engraftment. The probability of 12-month overall survival was 81.2%, reported Allyson Flower, MD, from Boston Children’s Health Physicians in Hawthorne, N.Y. “The probability of grade II-IV acute graft vs. host disease was 12.5%, compared with 32.5% seen with unrelated cord blood in our group’s previous studies. Cellular immune reconstitution was robust,” she said at the annual meeting of the American Society of Pediatric Hematology/Oncology.
Augmenting cord blood
Although unrelated donor cord blood transplantation expands the donor pool, is rapidly available, and is associated with decreases in both severe acute graft vs. host disease (GVHD) and chronic GVHD, compared with other stem cell sources, the technique is hampered by limited cell doses, prolonged immune reconstitution time, delays in hematopoietic recovery, and a higher incidence of graft failure.
Early studies of myeloablative conditioning followed by unrelated umbilical or placental blood transplantation showed a median of 22-24 days to neutrophil engraftment (Blood 1996 88:795-802; N Engl J Med. 1996;335:157-66), Dr. Flower noted.
More recently, a multivariate analysis of patients who underwent reduced-intensity conditioning followed by hematopoietic stem cell transplant with unrelated cord blood showed that graft failure was an independent risk factor for worse overall survival (Biol Blood Marrow Transplant. 2013 Apr;19:4;552-61).
Multiple groups have shown that adding human placenta–derived stem cells (HPDSC) to cord blood transplantation can facilitate more rapid hematopoietic engraftment by increasing the number of stem cells, increasing the proportion of hematopoietic progenitor cells, and providing additional, immature CD34+/CD45– progenitor cells.
In a single-arm, nonrandomized study, the investigators enrolled 16 patients ranging in age from 0.3 to 15.7 years with inborn errors of metabolism, marrow failure syndromes, severe immunodeficiency states, or hematologic malignancies.
Malignant conditions included B-cell precursor acute lymphoblastic leukemia (B-ALL; four patients), acute myeloid leukemia (AML; two), and T-cell ALL (one) in first complete remission, and T-cell lymphoblastic lymphoma following induction failure (one). Nonmalignant conditions included adrenoleukodystrophy (two patients), amegakaryotic thrombocytopenia (one), severe combined immunodeficiency (SCID; two), dyskeratosis congenita (one), chronic granulomatous disease (one), and severe congenital neutropenia (one).
The patients first underwent either myeloablative or reduced-intensity conditioning, followed 10 days later by infusion of unrelated cord blood and HPDSCs. Prior to HPDSC infusion, patients were medicated with diphenhydramine and hydrocortisone to prevent or reduce potential sensitivity reactions. HPDSCs were infused no sooner than 4 hours after the end of the cord blood infusion.
Patients received GVHD prophylaxis with either tacrolimus or cyclosporine, plus mycophenolate mofetil.
The combination appeared to be safe, with no cases of grade 3 or 4 toxicity secondary to HPDSC infusion.
The probability of neutrophil engraftment was 87.5%, with engraftment occurring at a median of 23 days (range 13-53). As noted before, all patients who had neutrophil engraftment had platelet engraftment, which was achieved at a median of 47 days (range, 20-98). In the group’s previous studies, median time to platelet engraftment was 53 days for patients who had undergone reduced-intensity conditioning, and 118 days for patients who had undergone myeloablation.
The probability of grade 2-4 acute GVHD within 100 days was 12.5%, and there were no cases of chronic GVHD.
Respective percentages of cord blood donor chimerism at days 30, 60, 100, and 180 were 88%, 98%, 99%, and 99%.
Immune reconstitution was strong, with normalization of mean CD3+, CD19+, and CD56+ cells occurring by day 100, CD8+ cells by day 180, and CD4+ cells by day 270.
There were three patient deaths: one from adenoviremia in a patient with B-ALL and CNS relapse, who had neutrophil engraftment at day 21; one in a patient with SCID, from adenoviremia and multiple system organ failure, who did not have engraftment before death; and one in a patient with severe congenital neutrophilia, who also did not have neutrophil engraftment.
None of the eight patients with malignant disease have experienced relapse to date, Dr. Flower noted.
The study was funded by a grant from Celgene Cellular Therapeutics. Dr. Flower reported having no conflicts of interest.
MONTREAL – A combination of placenta-derived stem cells and umbilical cord blood was associated with early engraftment and high degrees of cord blood donor chimerism in the treatment of children with both malignant and nonmalignant hematologic conditions requiring stem cell transplantation, updated results of a pilot study show.
Among 16 children treated with the combination, the probability of neutrophil engraftment was 87.5%, and all patients who had neutrophil engraftment went on to have platelet engraftment. The probability of 12-month overall survival was 81.2%, reported Allyson Flower, MD, from Boston Children’s Health Physicians in Hawthorne, N.Y. “The probability of grade II-IV acute graft vs. host disease was 12.5%, compared with 32.5% seen with unrelated cord blood in our group’s previous studies. Cellular immune reconstitution was robust,” she said at the annual meeting of the American Society of Pediatric Hematology/Oncology.
Augmenting cord blood
Although unrelated donor cord blood transplantation expands the donor pool, is rapidly available, and is associated with decreases in both severe acute graft vs. host disease (GVHD) and chronic GVHD, compared with other stem cell sources, the technique is hampered by limited cell doses, prolonged immune reconstitution time, delays in hematopoietic recovery, and a higher incidence of graft failure.
Early studies of myeloablative conditioning followed by unrelated umbilical or placental blood transplantation showed a median of 22-24 days to neutrophil engraftment (Blood 1996 88:795-802; N Engl J Med. 1996;335:157-66), Dr. Flower noted.
More recently, a multivariate analysis of patients who underwent reduced-intensity conditioning followed by hematopoietic stem cell transplant with unrelated cord blood showed that graft failure was an independent risk factor for worse overall survival (Biol Blood Marrow Transplant. 2013 Apr;19:4;552-61).
Multiple groups have shown that adding human placenta–derived stem cells (HPDSC) to cord blood transplantation can facilitate more rapid hematopoietic engraftment by increasing the number of stem cells, increasing the proportion of hematopoietic progenitor cells, and providing additional, immature CD34+/CD45– progenitor cells.
In a single-arm, nonrandomized study, the investigators enrolled 16 patients ranging in age from 0.3 to 15.7 years with inborn errors of metabolism, marrow failure syndromes, severe immunodeficiency states, or hematologic malignancies.
Malignant conditions included B-cell precursor acute lymphoblastic leukemia (B-ALL; four patients), acute myeloid leukemia (AML; two), and T-cell ALL (one) in first complete remission, and T-cell lymphoblastic lymphoma following induction failure (one). Nonmalignant conditions included adrenoleukodystrophy (two patients), amegakaryotic thrombocytopenia (one), severe combined immunodeficiency (SCID; two), dyskeratosis congenita (one), chronic granulomatous disease (one), and severe congenital neutropenia (one).
The patients first underwent either myeloablative or reduced-intensity conditioning, followed 10 days later by infusion of unrelated cord blood and HPDSCs. Prior to HPDSC infusion, patients were medicated with diphenhydramine and hydrocortisone to prevent or reduce potential sensitivity reactions. HPDSCs were infused no sooner than 4 hours after the end of the cord blood infusion.
Patients received GVHD prophylaxis with either tacrolimus or cyclosporine, plus mycophenolate mofetil.
The combination appeared to be safe, with no cases of grade 3 or 4 toxicity secondary to HPDSC infusion.
The probability of neutrophil engraftment was 87.5%, with engraftment occurring at a median of 23 days (range 13-53). As noted before, all patients who had neutrophil engraftment had platelet engraftment, which was achieved at a median of 47 days (range, 20-98). In the group’s previous studies, median time to platelet engraftment was 53 days for patients who had undergone reduced-intensity conditioning, and 118 days for patients who had undergone myeloablation.
The probability of grade 2-4 acute GVHD within 100 days was 12.5%, and there were no cases of chronic GVHD.
Respective percentages of cord blood donor chimerism at days 30, 60, 100, and 180 were 88%, 98%, 99%, and 99%.
Immune reconstitution was strong, with normalization of mean CD3+, CD19+, and CD56+ cells occurring by day 100, CD8+ cells by day 180, and CD4+ cells by day 270.
There were three patient deaths: one from adenoviremia in a patient with B-ALL and CNS relapse, who had neutrophil engraftment at day 21; one in a patient with SCID, from adenoviremia and multiple system organ failure, who did not have engraftment before death; and one in a patient with severe congenital neutrophilia, who also did not have neutrophil engraftment.
None of the eight patients with malignant disease have experienced relapse to date, Dr. Flower noted.
The study was funded by a grant from Celgene Cellular Therapeutics. Dr. Flower reported having no conflicts of interest.
Key clinical point: A combination of donor cord blood and human placenta–derived stem cells induced more rapid engraftment than cord blood alone.
Major finding: The probability of 12-month overall survival was 81%.
Data source: Open-label single-arm study in 16 children with severe malignant and nonmalignant diseases requiring hematopoietic stem cell transplants.
Disclosures: The study was funded by a grant from Celgene Cellular Therapeutics. Dr. Flower reported having no conflicts of interest.
Formaldehyde probably doesn’t cause leukemia, team says
There is little or no evidence to suggest that exposure to formaldehyde causes leukemia, according to a group of researchers.
The team reanalyzed data from a study published in 2010 that suggested a possible link between formaldehyde exposure and myeloid leukemia.
They also reviewed other recent studies investigating the health effects of formaldehyde.
“The weight of scientific evidence does not support a causal association between formaldehyde and leukemia,” said Kenneth A. Mundt, PhD, of Ramboll Environ, a consulting firm focused on environmental, health, and social issues.
Dr Mundt and his colleagues detailed the evidence in the Journal of Critical Reviews in Toxicology.
The team’s research was supported by the Foundation for Chemistry Research and Initiatives (formerly the Research Foundation for Health and Environmental Effects), an organization established by the American Chemistry Council (an industry trade association for American chemical companies).
The study that suggested a possible link between formaldehyde and myeloid leukemia, particularly acute myeloid leukemia (AML), was published in January 2010 in Cancer Epidemiology, Biomarkers & Prevention.
In this study, Luoping Zhang, PhD, of the University of California at Berkeley, and her colleagues compared 2 groups of workers in China—43 workers with occupational exposure to formaldehyde and 51 without such exposure.
The researchers looked at complete blood counts and peripheral stem/progenitor cell colony formation. They also cultured myeloid progenitor cells, aiming to determine the level of leukemia-specific chromosome changes, including monosomy 7 and trisomy 8, in these cells.
The team found that workers exposed to formaldehyde had significantly lower peripheral blood cell counts and significantly elevated leukemia-specific chromosome changes in myeloid progenitor cells.
Dr Zhang and her colleagues said these results suggest “formaldehyde exposure can have an adverse effect on the hematopoietic system and that leukemia induction by formaldehyde is biologically plausible.”
Dr Mundt and his colleagues reanalyzed raw data from this study, including previously unavailable data on individual workers’ exposure to formaldehyde. Those data were recently released by the National Cancer Institute, which co-funded Dr Zhang’s study.
The reanalysis indicated that the observed differences in blood cell counts were not dependent on formaldehyde exposure. And the researchers found no association between the individual average formaldehyde exposure estimates and chromosomal abnormalities.
Dr Mundt’s team also reviewed several other publications on the health effects of formaldehyde, and they said the data, as a whole, provide “little if any evidence of a causal association between formaldehyde exposure and AML.” 
There is little or no evidence to suggest that exposure to formaldehyde causes leukemia, according to a group of researchers.
The team reanalyzed data from a study published in 2010 that suggested a possible link between formaldehyde exposure and myeloid leukemia.
They also reviewed other recent studies investigating the health effects of formaldehyde.
“The weight of scientific evidence does not support a causal association between formaldehyde and leukemia,” said Kenneth A. Mundt, PhD, of Ramboll Environ, a consulting firm focused on environmental, health, and social issues.
Dr Mundt and his colleagues detailed the evidence in the Journal of Critical Reviews in Toxicology.
The team’s research was supported by the Foundation for Chemistry Research and Initiatives (formerly the Research Foundation for Health and Environmental Effects), an organization established by the American Chemistry Council (an industry trade association for American chemical companies).
The study that suggested a possible link between formaldehyde and myeloid leukemia, particularly acute myeloid leukemia (AML), was published in January 2010 in Cancer Epidemiology, Biomarkers & Prevention.
In this study, Luoping Zhang, PhD, of the University of California at Berkeley, and her colleagues compared 2 groups of workers in China—43 workers with occupational exposure to formaldehyde and 51 without such exposure.
The researchers looked at complete blood counts and peripheral stem/progenitor cell colony formation. They also cultured myeloid progenitor cells, aiming to determine the level of leukemia-specific chromosome changes, including monosomy 7 and trisomy 8, in these cells.
The team found that workers exposed to formaldehyde had significantly lower peripheral blood cell counts and significantly elevated leukemia-specific chromosome changes in myeloid progenitor cells.
Dr Zhang and her colleagues said these results suggest “formaldehyde exposure can have an adverse effect on the hematopoietic system and that leukemia induction by formaldehyde is biologically plausible.”
Dr Mundt and his colleagues reanalyzed raw data from this study, including previously unavailable data on individual workers’ exposure to formaldehyde. Those data were recently released by the National Cancer Institute, which co-funded Dr Zhang’s study.
The reanalysis indicated that the observed differences in blood cell counts were not dependent on formaldehyde exposure. And the researchers found no association between the individual average formaldehyde exposure estimates and chromosomal abnormalities.
Dr Mundt’s team also reviewed several other publications on the health effects of formaldehyde, and they said the data, as a whole, provide “little if any evidence of a causal association between formaldehyde exposure and AML.”
There is little or no evidence to suggest that exposure to formaldehyde causes leukemia, according to a group of researchers.
The team reanalyzed data from a study published in 2010 that suggested a possible link between formaldehyde exposure and myeloid leukemia.
They also reviewed other recent studies investigating the health effects of formaldehyde.
“The weight of scientific evidence does not support a causal association between formaldehyde and leukemia,” said Kenneth A. Mundt, PhD, of Ramboll Environ, a consulting firm focused on environmental, health, and social issues.
Dr Mundt and his colleagues detailed the evidence in the Journal of Critical Reviews in Toxicology.
The team’s research was supported by the Foundation for Chemistry Research and Initiatives (formerly the Research Foundation for Health and Environmental Effects), an organization established by the American Chemistry Council (an industry trade association for American chemical companies).
The study that suggested a possible link between formaldehyde and myeloid leukemia, particularly acute myeloid leukemia (AML), was published in January 2010 in Cancer Epidemiology, Biomarkers & Prevention.
In this study, Luoping Zhang, PhD, of the University of California at Berkeley, and her colleagues compared 2 groups of workers in China—43 workers with occupational exposure to formaldehyde and 51 without such exposure.
The researchers looked at complete blood counts and peripheral stem/progenitor cell colony formation. They also cultured myeloid progenitor cells, aiming to determine the level of leukemia-specific chromosome changes, including monosomy 7 and trisomy 8, in these cells.
The team found that workers exposed to formaldehyde had significantly lower peripheral blood cell counts and significantly elevated leukemia-specific chromosome changes in myeloid progenitor cells.
Dr Zhang and her colleagues said these results suggest “formaldehyde exposure can have an adverse effect on the hematopoietic system and that leukemia induction by formaldehyde is biologically plausible.”
Dr Mundt and his colleagues reanalyzed raw data from this study, including previously unavailable data on individual workers’ exposure to formaldehyde. Those data were recently released by the National Cancer Institute, which co-funded Dr Zhang’s study.
The reanalysis indicated that the observed differences in blood cell counts were not dependent on formaldehyde exposure. And the researchers found no association between the individual average formaldehyde exposure estimates and chromosomal abnormalities.
Dr Mundt’s team also reviewed several other publications on the health effects of formaldehyde, and they said the data, as a whole, provide “little if any evidence of a causal association between formaldehyde exposure and AML.”
Company withdraws MAA for vosaroxin in AML
Sunesis Pharmaceuticals, Inc. is withdrawing its European Marketing Authorization Application (MAA) for the anticancer quinolone derivative vosaroxin.
The MAA was for vosaroxin as a treatment for relapsed/refractory acute myeloid leukemia (AML) in patients age 60 years and older.
Along with the MAA withdrawal, Sunesis has decided to scale back its investment in vosaroxin.
However, the company said it will continue developing the drug.
These decisions were made after Sunesis learned the European Medicine Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) was unlikely to recommend approval for vosaroxin.
“We are disappointed to not achieve approval for vosaroxin’s MAA, given its reported efficacy in a patient population with such poor outcomes,” said Daniel Swisher, president and chief executive officer of Sunesis.
“Although we did not receive a definitive CHMP opinion, we believed that a positive opinion was unlikely. Following our appearances before the committee’s Scientific Advisory Group on Oncology and CHMP, we carefully considered feedback from our rapporteurs and input from retained regulatory experts to make our decision to notify EMA to withdraw vosaroxin’s MAA, as our assessment concluded it was unlikely we could achieve a majority vote of CHMP members at this time or upon an immediate re-examination for our proposed indication based on VALOR data from a subgroup of a single pivotal trial that had missed reaching full statistical significance in its primary analysis.”
“In light of this, we are significantly reducing our investment in the AML program and shifting an increasing portion of resources to our kinase inhibitor pipeline . . . . We expect to continue to advance the development of vosaroxin through a modest investment in investigator-sponsored group trials and will carefully assess business development alternatives to support the conduct of another pivotal trial to achieve future regulatory approval of vosaroxin. We expect that our current cash resources are sufficient to fund the company beyond Q1 2018.”
Sunesis Pharmaceuticals, Inc. is withdrawing its European Marketing Authorization Application (MAA) for the anticancer quinolone derivative vosaroxin.
The MAA was for vosaroxin as a treatment for relapsed/refractory acute myeloid leukemia (AML) in patients age 60 years and older.
Along with the MAA withdrawal, Sunesis has decided to scale back its investment in vosaroxin.
However, the company said it will continue developing the drug.
These decisions were made after Sunesis learned the European Medicine Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) was unlikely to recommend approval for vosaroxin.
“We are disappointed to not achieve approval for vosaroxin’s MAA, given its reported efficacy in a patient population with such poor outcomes,” said Daniel Swisher, president and chief executive officer of Sunesis.
“Although we did not receive a definitive CHMP opinion, we believed that a positive opinion was unlikely. Following our appearances before the committee’s Scientific Advisory Group on Oncology and CHMP, we carefully considered feedback from our rapporteurs and input from retained regulatory experts to make our decision to notify EMA to withdraw vosaroxin’s MAA, as our assessment concluded it was unlikely we could achieve a majority vote of CHMP members at this time or upon an immediate re-examination for our proposed indication based on VALOR data from a subgroup of a single pivotal trial that had missed reaching full statistical significance in its primary analysis.”
“In light of this, we are significantly reducing our investment in the AML program and shifting an increasing portion of resources to our kinase inhibitor pipeline . . . . We expect to continue to advance the development of vosaroxin through a modest investment in investigator-sponsored group trials and will carefully assess business development alternatives to support the conduct of another pivotal trial to achieve future regulatory approval of vosaroxin. We expect that our current cash resources are sufficient to fund the company beyond Q1 2018.”
Sunesis Pharmaceuticals, Inc. is withdrawing its European Marketing Authorization Application (MAA) for the anticancer quinolone derivative vosaroxin.
The MAA was for vosaroxin as a treatment for relapsed/refractory acute myeloid leukemia (AML) in patients age 60 years and older.
Along with the MAA withdrawal, Sunesis has decided to scale back its investment in vosaroxin.
However, the company said it will continue developing the drug.
These decisions were made after Sunesis learned the European Medicine Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) was unlikely to recommend approval for vosaroxin.
“We are disappointed to not achieve approval for vosaroxin’s MAA, given its reported efficacy in a patient population with such poor outcomes,” said Daniel Swisher, president and chief executive officer of Sunesis.
“Although we did not receive a definitive CHMP opinion, we believed that a positive opinion was unlikely. Following our appearances before the committee’s Scientific Advisory Group on Oncology and CHMP, we carefully considered feedback from our rapporteurs and input from retained regulatory experts to make our decision to notify EMA to withdraw vosaroxin’s MAA, as our assessment concluded it was unlikely we could achieve a majority vote of CHMP members at this time or upon an immediate re-examination for our proposed indication based on VALOR data from a subgroup of a single pivotal trial that had missed reaching full statistical significance in its primary analysis.”
“In light of this, we are significantly reducing our investment in the AML program and shifting an increasing portion of resources to our kinase inhibitor pipeline . . . . We expect to continue to advance the development of vosaroxin through a modest investment in investigator-sponsored group trials and will carefully assess business development alternatives to support the conduct of another pivotal trial to achieve future regulatory approval of vosaroxin. We expect that our current cash resources are sufficient to fund the company beyond Q1 2018.”
Heavily promoted drugs provide less ‘health value,’ study suggests
Drugs that are promoted most heavily in the US are less likely than the top-selling drugs and the top-prescribed drugs to provide “health value,” according to researchers.
The top-promoted drugs were less likely than either or both of the other drug types to demonstrate safety and effectiveness, be affordable, represent a genuine advance in treating a disease, be included on the World Health Organization’s (WHO) list of essential medicines, or be recommended as a first-line treatment.
Among the top-promoted drugs were 4 anticoagulants—Eliquis (apixaban), Xarelto (rivaroxaban), Brilinta (ticagrelor), and Pradaxa (dabigatran).
Tyler Greenway and Joseph S. Ross, MD, both of Yale University School of Medicine in New Haven, Connecticut, conducted this research and reported their findings in The BMJ.
The researchers set out to assess the “health value” of the drugs most aggressively promoted to physicians to better understand the implications of pharmaceutical promotion for patient care.
The team identified the 25 medicinal products associated with the largest total payments to physicians and teaching hospitals from August 2013 to December 2014.
This included all direct and indirect payments, such as speaker fees for education lectures, consulting fees, and honoraria, as well as payments in kind, such as the value of food and gifts. However, research payments, royalties, and licensing fees were excluded, as these are typically not promotional.
The researchers also determined the 25 best-selling medicinal products by 2014 US sales and the 25 most-prescribed drugs in the US during 2013.
One of the 25 top-promoted products was excluded because it was used to test for adrenocortical function. And 1 of the 25 top-selling products was a pneumococcal vaccine, which was also excluded.
Four of the 24 top-promoted drugs (17%) were also among the top-selling drugs—adalimumab, glatiramer, aripiprazole, and budesonide-formoterol. But none of the top-promoted drugs were among the top-prescribed drugs.
Among the top-selling drugs were several used in the field of hematology—Rituxan (rituximab), Neulasta (pegfilgrastim), Neupogen (filgrastim), Revlimid (lenalidomide), and Gleevec (imatinib mesylate).
Results
The researchers estimated the drugs’ value to society using 5 proxy measures:
- Innovation—drugs that were first-in-class or provided a “meaningful advance” over existing treatments
- Effectiveness and safety—assessed using the ratings systems of the French drug industry watchdog Prescrire International
- Generic availability—a measure of affordability
- Clinical value—inclusion on the WHO list of essential medicines in 2015
- First-line status—being recommended as a first-line therapy.
The top-promoted drugs were significantly less likely to be considered innovative than the top-selling drugs (33% vs 72%, relative risk [RR]=0.46, P=0.01). However, the difference was not significant for the top-promoted and top-prescribed drugs (33% vs 52%, RR=0.64, P=0.25).
The top-promoted drugs were significantly less likely to be considered possibly helpful or advantageous according to Prescrire ratings than the top-prescribed drugs (19% vs 76%, RR=0.25, P<0.001). But the difference was not significant for the top-promoted and top-selling drugs (19% vs 44%, RR=0.43, P=0.11).
Generic equivalents were available for 62% of the top-promoted drugs, 32% of the top-selling drugs (RR=1.95, P=0.05), and 100% of the top-prescribed drugs (RR=0.63, P<0.001).
The top-promoted drugs were significantly less likely than either of the other drug types to be on the WHO essential medicines list. One of the top-promoted drugs was on the list, compared to 9 top-selling drugs (RR=0.12, P=0.01) and 14 top-prescribed drugs (RR=0.07, P<0.001).
The top-promoted drugs were significantly less likely to be recommended as first-line treatments than the top-prescribed drugs (33% vs 80%, RR=0.42, P=0.001). But the difference was not significant for the top-selling drugs (33% vs 60%, RR=0.56, P=0.09).
The researchers said these results raise concerns about the purpose of pharmaceutical promotion and its influence on patient care. They believe efforts are needed to better evaluate the value of drugs, ensuring this information is readily available at the point of care so it can inform clinical decision-making and promote the use of higher-value medicines.
The researchers also suggested that clinicians consider taking steps to limit their exposure to industry promotion and consider engaging with non-commercial educational outreach programs that provide evidence-based recommendations about medication choices.
Drugs that are promoted most heavily in the US are less likely than the top-selling drugs and the top-prescribed drugs to provide “health value,” according to researchers.
The top-promoted drugs were less likely than either or both of the other drug types to demonstrate safety and effectiveness, be affordable, represent a genuine advance in treating a disease, be included on the World Health Organization’s (WHO) list of essential medicines, or be recommended as a first-line treatment.
Among the top-promoted drugs were 4 anticoagulants—Eliquis (apixaban), Xarelto (rivaroxaban), Brilinta (ticagrelor), and Pradaxa (dabigatran).
Tyler Greenway and Joseph S. Ross, MD, both of Yale University School of Medicine in New Haven, Connecticut, conducted this research and reported their findings in The BMJ.
The researchers set out to assess the “health value” of the drugs most aggressively promoted to physicians to better understand the implications of pharmaceutical promotion for patient care.
The team identified the 25 medicinal products associated with the largest total payments to physicians and teaching hospitals from August 2013 to December 2014.
This included all direct and indirect payments, such as speaker fees for education lectures, consulting fees, and honoraria, as well as payments in kind, such as the value of food and gifts. However, research payments, royalties, and licensing fees were excluded, as these are typically not promotional.
The researchers also determined the 25 best-selling medicinal products by 2014 US sales and the 25 most-prescribed drugs in the US during 2013.
One of the 25 top-promoted products was excluded because it was used to test for adrenocortical function. And 1 of the 25 top-selling products was a pneumococcal vaccine, which was also excluded.
Four of the 24 top-promoted drugs (17%) were also among the top-selling drugs—adalimumab, glatiramer, aripiprazole, and budesonide-formoterol. But none of the top-promoted drugs were among the top-prescribed drugs.
Among the top-selling drugs were several used in the field of hematology—Rituxan (rituximab), Neulasta (pegfilgrastim), Neupogen (filgrastim), Revlimid (lenalidomide), and Gleevec (imatinib mesylate).
Results
The researchers estimated the drugs’ value to society using 5 proxy measures:
- Innovation—drugs that were first-in-class or provided a “meaningful advance” over existing treatments
- Effectiveness and safety—assessed using the ratings systems of the French drug industry watchdog Prescrire International
- Generic availability—a measure of affordability
- Clinical value—inclusion on the WHO list of essential medicines in 2015
- First-line status—being recommended as a first-line therapy.
The top-promoted drugs were significantly less likely to be considered innovative than the top-selling drugs (33% vs 72%, relative risk [RR]=0.46, P=0.01). However, the difference was not significant for the top-promoted and top-prescribed drugs (33% vs 52%, RR=0.64, P=0.25).
The top-promoted drugs were significantly less likely to be considered possibly helpful or advantageous according to Prescrire ratings than the top-prescribed drugs (19% vs 76%, RR=0.25, P<0.001). But the difference was not significant for the top-promoted and top-selling drugs (19% vs 44%, RR=0.43, P=0.11).
Generic equivalents were available for 62% of the top-promoted drugs, 32% of the top-selling drugs (RR=1.95, P=0.05), and 100% of the top-prescribed drugs (RR=0.63, P<0.001).
The top-promoted drugs were significantly less likely than either of the other drug types to be on the WHO essential medicines list. One of the top-promoted drugs was on the list, compared to 9 top-selling drugs (RR=0.12, P=0.01) and 14 top-prescribed drugs (RR=0.07, P<0.001).
The top-promoted drugs were significantly less likely to be recommended as first-line treatments than the top-prescribed drugs (33% vs 80%, RR=0.42, P=0.001). But the difference was not significant for the top-selling drugs (33% vs 60%, RR=0.56, P=0.09).
The researchers said these results raise concerns about the purpose of pharmaceutical promotion and its influence on patient care. They believe efforts are needed to better evaluate the value of drugs, ensuring this information is readily available at the point of care so it can inform clinical decision-making and promote the use of higher-value medicines.
The researchers also suggested that clinicians consider taking steps to limit their exposure to industry promotion and consider engaging with non-commercial educational outreach programs that provide evidence-based recommendations about medication choices.
Drugs that are promoted most heavily in the US are less likely than the top-selling drugs and the top-prescribed drugs to provide “health value,” according to researchers.
The top-promoted drugs were less likely than either or both of the other drug types to demonstrate safety and effectiveness, be affordable, represent a genuine advance in treating a disease, be included on the World Health Organization’s (WHO) list of essential medicines, or be recommended as a first-line treatment.
Among the top-promoted drugs were 4 anticoagulants—Eliquis (apixaban), Xarelto (rivaroxaban), Brilinta (ticagrelor), and Pradaxa (dabigatran).
Tyler Greenway and Joseph S. Ross, MD, both of Yale University School of Medicine in New Haven, Connecticut, conducted this research and reported their findings in The BMJ.
The researchers set out to assess the “health value” of the drugs most aggressively promoted to physicians to better understand the implications of pharmaceutical promotion for patient care.
The team identified the 25 medicinal products associated with the largest total payments to physicians and teaching hospitals from August 2013 to December 2014.
This included all direct and indirect payments, such as speaker fees for education lectures, consulting fees, and honoraria, as well as payments in kind, such as the value of food and gifts. However, research payments, royalties, and licensing fees were excluded, as these are typically not promotional.
The researchers also determined the 25 best-selling medicinal products by 2014 US sales and the 25 most-prescribed drugs in the US during 2013.
One of the 25 top-promoted products was excluded because it was used to test for adrenocortical function. And 1 of the 25 top-selling products was a pneumococcal vaccine, which was also excluded.
Four of the 24 top-promoted drugs (17%) were also among the top-selling drugs—adalimumab, glatiramer, aripiprazole, and budesonide-formoterol. But none of the top-promoted drugs were among the top-prescribed drugs.
Among the top-selling drugs were several used in the field of hematology—Rituxan (rituximab), Neulasta (pegfilgrastim), Neupogen (filgrastim), Revlimid (lenalidomide), and Gleevec (imatinib mesylate).
Results
The researchers estimated the drugs’ value to society using 5 proxy measures:
- Innovation—drugs that were first-in-class or provided a “meaningful advance” over existing treatments
- Effectiveness and safety—assessed using the ratings systems of the French drug industry watchdog Prescrire International
- Generic availability—a measure of affordability
- Clinical value—inclusion on the WHO list of essential medicines in 2015
- First-line status—being recommended as a first-line therapy.
The top-promoted drugs were significantly less likely to be considered innovative than the top-selling drugs (33% vs 72%, relative risk [RR]=0.46, P=0.01). However, the difference was not significant for the top-promoted and top-prescribed drugs (33% vs 52%, RR=0.64, P=0.25).
The top-promoted drugs were significantly less likely to be considered possibly helpful or advantageous according to Prescrire ratings than the top-prescribed drugs (19% vs 76%, RR=0.25, P<0.001). But the difference was not significant for the top-promoted and top-selling drugs (19% vs 44%, RR=0.43, P=0.11).
Generic equivalents were available for 62% of the top-promoted drugs, 32% of the top-selling drugs (RR=1.95, P=0.05), and 100% of the top-prescribed drugs (RR=0.63, P<0.001).
The top-promoted drugs were significantly less likely than either of the other drug types to be on the WHO essential medicines list. One of the top-promoted drugs was on the list, compared to 9 top-selling drugs (RR=0.12, P=0.01) and 14 top-prescribed drugs (RR=0.07, P<0.001).
The top-promoted drugs were significantly less likely to be recommended as first-line treatments than the top-prescribed drugs (33% vs 80%, RR=0.42, P=0.001). But the difference was not significant for the top-selling drugs (33% vs 60%, RR=0.56, P=0.09).
The researchers said these results raise concerns about the purpose of pharmaceutical promotion and its influence on patient care. They believe efforts are needed to better evaluate the value of drugs, ensuring this information is readily available at the point of care so it can inform clinical decision-making and promote the use of higher-value medicines.
The researchers also suggested that clinicians consider taking steps to limit their exposure to industry promotion and consider engaging with non-commercial educational outreach programs that provide evidence-based recommendations about medication choices.
Demystifying interstitial cystitis
Chronic pelvic pain continues not only to burden the individual, but society as well.
One in seven women between the ages of 18 and 50 endure chronic pelvic pain; with a lifetime incidence of as high as 33%, according to one Gallup poll. Interstitial cystitis/bladder pain syndrome (IC/BPS) has been estimated to have a prevalence of 850 in 100,000 women and 60 in 100,000 men in self-report studies. The RAND Interstitial Cystitis Epidemiology (RICE) study, a symptoms survey, showed that between 2.7% and 6.5% of women (3.3 to 7.9 million women) in the United States have symptoms consistent with a diagnosis of IC/BPS.
Unfortunately, there is little known about the etiology and pathogenesis of IC/PBS. Moreover, oftentimes, the diagnosis is one of exclusion.
To demystify interstitial cystitis/bladder pain syndrome, I have elicited the assistance of Dr. Kenneth Peters, a urologist on staff at William Beaumont Hospital, Royal Oak, Mich. Dr. Peters is the professor and chairman of urology at Oakland University, William Beaumont School of Medicine, and the chairman of urology at Beaumont Health, Royal Oak, Mich.
In his discussion, Dr. Peters will point out that interstitial cystitis actually consists of two different entities: a classic presentation featuring the pathognomonic Hunner’s lesion on cystoscopy and interstitial cystitis/painful bladder syndrome.
It must be acknowledged that Dr. Peters is a practicing urologist. Therefore, some of his recommendations, such as cauterizing Hunner’s lesions via a resectoscope, are beyond the scope of practicing gynecologists. However, it is important for us to realize what our potential referrals possess in their armamentarium. Moreover, it is obvious there is much that can be learned from this excellent diagnostician who professes the importance of physical examination.
Dr. Miller is clinical associate professor at the University of Illinois at Chicago, and past president of the AAGL. He is a reproductive endocrinologist and minimally invasive gynecologic surgeon in metropolitan Chicago; director of minimally invasive gynecologic surgery at Advocate Lutheran General Hospital, Park Ridge, Ill.; and the medical editor of this column. He is an investigator on an interstitial cystitis study sponsored by Allergan.
Chronic pelvic pain continues not only to burden the individual, but society as well.
One in seven women between the ages of 18 and 50 endure chronic pelvic pain; with a lifetime incidence of as high as 33%, according to one Gallup poll. Interstitial cystitis/bladder pain syndrome (IC/BPS) has been estimated to have a prevalence of 850 in 100,000 women and 60 in 100,000 men in self-report studies. The RAND Interstitial Cystitis Epidemiology (RICE) study, a symptoms survey, showed that between 2.7% and 6.5% of women (3.3 to 7.9 million women) in the United States have symptoms consistent with a diagnosis of IC/BPS.
Unfortunately, there is little known about the etiology and pathogenesis of IC/PBS. Moreover, oftentimes, the diagnosis is one of exclusion.
To demystify interstitial cystitis/bladder pain syndrome, I have elicited the assistance of Dr. Kenneth Peters, a urologist on staff at William Beaumont Hospital, Royal Oak, Mich. Dr. Peters is the professor and chairman of urology at Oakland University, William Beaumont School of Medicine, and the chairman of urology at Beaumont Health, Royal Oak, Mich.
In his discussion, Dr. Peters will point out that interstitial cystitis actually consists of two different entities: a classic presentation featuring the pathognomonic Hunner’s lesion on cystoscopy and interstitial cystitis/painful bladder syndrome.
It must be acknowledged that Dr. Peters is a practicing urologist. Therefore, some of his recommendations, such as cauterizing Hunner’s lesions via a resectoscope, are beyond the scope of practicing gynecologists. However, it is important for us to realize what our potential referrals possess in their armamentarium. Moreover, it is obvious there is much that can be learned from this excellent diagnostician who professes the importance of physical examination.
Dr. Miller is clinical associate professor at the University of Illinois at Chicago, and past president of the AAGL. He is a reproductive endocrinologist and minimally invasive gynecologic surgeon in metropolitan Chicago; director of minimally invasive gynecologic surgery at Advocate Lutheran General Hospital, Park Ridge, Ill.; and the medical editor of this column. He is an investigator on an interstitial cystitis study sponsored by Allergan.
Chronic pelvic pain continues not only to burden the individual, but society as well.
One in seven women between the ages of 18 and 50 endure chronic pelvic pain; with a lifetime incidence of as high as 33%, according to one Gallup poll. Interstitial cystitis/bladder pain syndrome (IC/BPS) has been estimated to have a prevalence of 850 in 100,000 women and 60 in 100,000 men in self-report studies. The RAND Interstitial Cystitis Epidemiology (RICE) study, a symptoms survey, showed that between 2.7% and 6.5% of women (3.3 to 7.9 million women) in the United States have symptoms consistent with a diagnosis of IC/BPS.
Unfortunately, there is little known about the etiology and pathogenesis of IC/PBS. Moreover, oftentimes, the diagnosis is one of exclusion.
To demystify interstitial cystitis/bladder pain syndrome, I have elicited the assistance of Dr. Kenneth Peters, a urologist on staff at William Beaumont Hospital, Royal Oak, Mich. Dr. Peters is the professor and chairman of urology at Oakland University, William Beaumont School of Medicine, and the chairman of urology at Beaumont Health, Royal Oak, Mich.
In his discussion, Dr. Peters will point out that interstitial cystitis actually consists of two different entities: a classic presentation featuring the pathognomonic Hunner’s lesion on cystoscopy and interstitial cystitis/painful bladder syndrome.
It must be acknowledged that Dr. Peters is a practicing urologist. Therefore, some of his recommendations, such as cauterizing Hunner’s lesions via a resectoscope, are beyond the scope of practicing gynecologists. However, it is important for us to realize what our potential referrals possess in their armamentarium. Moreover, it is obvious there is much that can be learned from this excellent diagnostician who professes the importance of physical examination.
Dr. Miller is clinical associate professor at the University of Illinois at Chicago, and past president of the AAGL. He is a reproductive endocrinologist and minimally invasive gynecologic surgeon in metropolitan Chicago; director of minimally invasive gynecologic surgery at Advocate Lutheran General Hospital, Park Ridge, Ill.; and the medical editor of this column. He is an investigator on an interstitial cystitis study sponsored by Allergan.
