Hospitalists should not only lead efforts to control potential Ebola outbreaks in the U.S. but should also play a role in improving global healthcare, say the authors of a recent article in the Journal of Hospital Medicine.

Author Phuoc Le, MD, MPH, assistant professor of medicine and pediatrics at the University of California San Francisco where he co-directs the Global Health-Hospital Medicine Fellowship, is also cofounder of the HEAL Initiative, a global healthcare campaign designed to improve the health of vulnerable populations worldwide. HEAL, short for Health, Equity, Action, and Leadership, recently won the 2015 SHM Award for Excellence in Humanitarian Service.

Dr. Le recently spoke with TH about why hospitalists are well-equipped to handle global health problems.

Question: In your paper, you call on hospitalists to join the ranks of global health hospitalists. Can you explain?

Answer: Whether it’s Navajo Nation in Arizona or rural Haiti, the healthcare needs of the poor are very similar. Global health hospitalists play an important role in building capacity, running a health system, improving quality while reducing costs, working in teams to provide holistic care for the inpatient, and improving transitions to the outpatient setting.

Q: How do the skills learned in resource-poor settings apply back home?

A: Let's say you have a patient with tuberculosis, which is very common in places like Liberia, and you suspect fluid in the lungs. [In Liberia], you would insert a needle and remove the fluid. In the U.S., a lot of providers would not be able to remove the fluid without getting an ultrasound and multiple other studies. Those costs add up. Global health hospitalists are very well-versed in the skills of ultrasonography because there are no ultrasonographers in the field working with us.

Q: You've spent time in Haiti and said that is where you began to notice volunteers arriving with good intentions but without needed skills. What exactly did you learn?

A: I spent a lot of time there, responding to the earthquake and also the cholera epidemic in 2010. I came across dozens of healthcare volunteers who had passion and commitment but really came ill-prepared, not through any fault of their own but because they never had an opportunity to learn the skills needed to be effective in the field. For example, take a nurse from an ivory-tower hospital and suddenly put her where she doesn’t have IVs to work with or the right type of fluids or tubing. Well, suddenly she feels like her efficacy has gone way down. That could easily lead to a lot of frustration and potential burnout. That’s why we started the HEAL Initiative, which is a two-year program for healthcare workers who want to learn the skills needed to work in poor settings.

Q: How can hospitalists get involved in global health?

A: Come to the Society of Hospital Medicine annual meeting in March where we’ll be hosting a special-interest session called Global Health and Human Rights.

Visit our website for more information about global health hospitalists.

Hospitalists should not only lead efforts to control potential Ebola outbreaks in the U.S. but should also play a role in improving global healthcare, say the authors of a recent article in the Journal of Hospital Medicine.

Author Phuoc Le, MD, MPH, assistant professor of medicine and pediatrics at the University of California San Francisco where he co-directs the Global Health-Hospital Medicine Fellowship, is also cofounder of the HEAL Initiative, a global healthcare campaign designed to improve the health of vulnerable populations worldwide. HEAL, short for Health, Equity, Action, and Leadership, recently won the 2015 SHM Award for Excellence in Humanitarian Service.

Dr. Le recently spoke with TH about why hospitalists are well-equipped to handle global health problems.

Question: In your paper, you call on hospitalists to join the ranks of global health hospitalists. Can you explain?

Answer: Whether it’s Navajo Nation in Arizona or rural Haiti, the healthcare needs of the poor are very similar. Global health hospitalists play an important role in building capacity, running a health system, improving quality while reducing costs, working in teams to provide holistic care for the inpatient, and improving transitions to the outpatient setting.

Q: How do the skills learned in resource-poor settings apply back home?

A: Let's say you have a patient with tuberculosis, which is very common in places like Liberia, and you suspect fluid in the lungs. [In Liberia], you would insert a needle and remove the fluid. In the U.S., a lot of providers would not be able to remove the fluid without getting an ultrasound and multiple other studies. Those costs add up. Global health hospitalists are very well-versed in the skills of ultrasonography because there are no ultrasonographers in the field working with us.

Q: You've spent time in Haiti and said that is where you began to notice volunteers arriving with good intentions but without needed skills. What exactly did you learn?

A: I spent a lot of time there, responding to the earthquake and also the cholera epidemic in 2010. I came across dozens of healthcare volunteers who had passion and commitment but really came ill-prepared, not through any fault of their own but because they never had an opportunity to learn the skills needed to be effective in the field. For example, take a nurse from an ivory-tower hospital and suddenly put her where she doesn’t have IVs to work with or the right type of fluids or tubing. Well, suddenly she feels like her efficacy has gone way down. That could easily lead to a lot of frustration and potential burnout. That’s why we started the HEAL Initiative, which is a two-year program for healthcare workers who want to learn the skills needed to work in poor settings.

Q: How can hospitalists get involved in global health?

A: Come to the Society of Hospital Medicine annual meeting in March where we’ll be hosting a special-interest session called Global Health and Human Rights.

Visit our website for more information about global health hospitalists.

Hospitalists should not only lead efforts to control potential Ebola outbreaks in the U.S. but should also play a role in improving global healthcare, say the authors of a recent article in the Journal of Hospital Medicine.

Author Phuoc Le, MD, MPH, assistant professor of medicine and pediatrics at the University of California San Francisco where he co-directs the Global Health-Hospital Medicine Fellowship, is also cofounder of the HEAL Initiative, a global healthcare campaign designed to improve the health of vulnerable populations worldwide. HEAL, short for Health, Equity, Action, and Leadership, recently won the 2015 SHM Award for Excellence in Humanitarian Service.

Dr. Le recently spoke with TH about why hospitalists are well-equipped to handle global health problems.

Question: In your paper, you call on hospitalists to join the ranks of global health hospitalists. Can you explain?

Answer: Whether it’s Navajo Nation in Arizona or rural Haiti, the healthcare needs of the poor are very similar. Global health hospitalists play an important role in building capacity, running a health system, improving quality while reducing costs, working in teams to provide holistic care for the inpatient, and improving transitions to the outpatient setting.

Q: How do the skills learned in resource-poor settings apply back home?

A: Let's say you have a patient with tuberculosis, which is very common in places like Liberia, and you suspect fluid in the lungs. [In Liberia], you would insert a needle and remove the fluid. In the U.S., a lot of providers would not be able to remove the fluid without getting an ultrasound and multiple other studies. Those costs add up. Global health hospitalists are very well-versed in the skills of ultrasonography because there are no ultrasonographers in the field working with us.

Q: You've spent time in Haiti and said that is where you began to notice volunteers arriving with good intentions but without needed skills. What exactly did you learn?

A: I spent a lot of time there, responding to the earthquake and also the cholera epidemic in 2010. I came across dozens of healthcare volunteers who had passion and commitment but really came ill-prepared, not through any fault of their own but because they never had an opportunity to learn the skills needed to be effective in the field. For example, take a nurse from an ivory-tower hospital and suddenly put her where she doesn’t have IVs to work with or the right type of fluids or tubing. Well, suddenly she feels like her efficacy has gone way down. That could easily lead to a lot of frustration and potential burnout. That’s why we started the HEAL Initiative, which is a two-year program for healthcare workers who want to learn the skills needed to work in poor settings.

Q: How can hospitalists get involved in global health?

A: Come to the Society of Hospital Medicine annual meeting in March where we’ll be hosting a special-interest session called Global Health and Human Rights.

Visit our website for more information about global health hospitalists.

News that the American Board of Internal Medicine (ABIM) will reboot its controversial Maintenance of Certification (MOC) program is an opportunity for hospitalists to help shape their own professional development, according to former ABIM chair and hospital medicine pioneer Robert Wachter, MD, MHM.

A year ago, ABIM moved from an MOC every 10 years to a more continuous certification process. The goal was to keep physicians more current, but the change sparked backlash over education costs, the applicability and usefulness of exam questions, and bureaucratic burdens of the new process.

In a public statement last week, ABIM president and CEO Richard Baron, MD, acknowledged that "ABIM clearly got it wrong. We launched programs that weren't ready and we didn't deliver an MOC program that physicians found meaningful."

Dr. Wachter, who was ABIM's chair when Dr. Baron was hired, says that ABIM's new plan to reach out to specialty societies means SHM can lobby for an MOC process that is more current, more applicable, and more meaningful to practitioners. Given that HM as a specialty was launched as a novel idea on what would make a good care model for hospitalized patients, Dr. Wachter is confident that SHM can be helpful in guiding the creation of a better MOC process.

Hospital medicine "was built on out-of-the-box thinking, on accepting certain parts of the old model of what a good doctor was but throwing other parts out and saying, 'We want to rethink this,'" Dr. Wachter says. "I can't think of a specialty that’s better positioned to help."

Meanwhile, hospitalist and ABIM Council member Jeff Wiese, MD, MHM, sees an opportunity to make sure the overall process for "knowledge improvement" is enhanced so that disconnects between practitioners and ABIM do not continue.

"We have to ensure that what happened over the past 20 years doesn't happen again," Dr. Wiese says. "Namely, that the world of medicine doesn't move so fast that the ABIM MOC requirements don't keep up. If we engage as physicians and specialty organizations in meaningful dialogues…then we have a much better chance of making MOC sufficiently dynamic to meet the changing times."

SHM President Burke Kealey, MD, SFHM, says that hospitalists were less impacted than some other specialists by the MOC change because they could use the Focused Practice in Hospital Medicine (FPHM) exam. The FPHM test was crafted by "real practicing hospitalists [writing] the questions for hospitalists from the point of view of what a hospitalist needs to know to do their job," he says.

Dr. Kealey adds that SHM plans to help hospitalists prepare for exams through courses featured at next month’s annual meeting and with the publication of a study guide due out this fall focused on the test's nonclinical aspects. Since it was posted last week, Dr. Kealey's blog on "The Hospital Leader" has attracted the interest of thousands of hospitalists and has been shared more than 70 times.

Visit our website for more information on Maintenance of Certification issues.

News that the American Board of Internal Medicine (ABIM) will reboot its controversial Maintenance of Certification (MOC) program is an opportunity for hospitalists to help shape their own professional development, according to former ABIM chair and hospital medicine pioneer Robert Wachter, MD, MHM.

A year ago, ABIM moved from an MOC every 10 years to a more continuous certification process. The goal was to keep physicians more current, but the change sparked backlash over education costs, the applicability and usefulness of exam questions, and bureaucratic burdens of the new process.

In a public statement last week, ABIM president and CEO Richard Baron, MD, acknowledged that "ABIM clearly got it wrong. We launched programs that weren't ready and we didn't deliver an MOC program that physicians found meaningful."

Dr. Wachter, who was ABIM's chair when Dr. Baron was hired, says that ABIM's new plan to reach out to specialty societies means SHM can lobby for an MOC process that is more current, more applicable, and more meaningful to practitioners. Given that HM as a specialty was launched as a novel idea on what would make a good care model for hospitalized patients, Dr. Wachter is confident that SHM can be helpful in guiding the creation of a better MOC process.

Hospital medicine "was built on out-of-the-box thinking, on accepting certain parts of the old model of what a good doctor was but throwing other parts out and saying, 'We want to rethink this,'" Dr. Wachter says. "I can't think of a specialty that’s better positioned to help."

Meanwhile, hospitalist and ABIM Council member Jeff Wiese, MD, MHM, sees an opportunity to make sure the overall process for "knowledge improvement" is enhanced so that disconnects between practitioners and ABIM do not continue.

"We have to ensure that what happened over the past 20 years doesn't happen again," Dr. Wiese says. "Namely, that the world of medicine doesn't move so fast that the ABIM MOC requirements don't keep up. If we engage as physicians and specialty organizations in meaningful dialogues…then we have a much better chance of making MOC sufficiently dynamic to meet the changing times."

SHM President Burke Kealey, MD, SFHM, says that hospitalists were less impacted than some other specialists by the MOC change because they could use the Focused Practice in Hospital Medicine (FPHM) exam. The FPHM test was crafted by "real practicing hospitalists [writing] the questions for hospitalists from the point of view of what a hospitalist needs to know to do their job," he says.

Dr. Kealey adds that SHM plans to help hospitalists prepare for exams through courses featured at next month’s annual meeting and with the publication of a study guide due out this fall focused on the test's nonclinical aspects. Since it was posted last week, Dr. Kealey's blog on "The Hospital Leader" has attracted the interest of thousands of hospitalists and has been shared more than 70 times.

Visit our website for more information on Maintenance of Certification issues.

News that the American Board of Internal Medicine (ABIM) will reboot its controversial Maintenance of Certification (MOC) program is an opportunity for hospitalists to help shape their own professional development, according to former ABIM chair and hospital medicine pioneer Robert Wachter, MD, MHM.

A year ago, ABIM moved from an MOC every 10 years to a more continuous certification process. The goal was to keep physicians more current, but the change sparked backlash over education costs, the applicability and usefulness of exam questions, and bureaucratic burdens of the new process.

In a public statement last week, ABIM president and CEO Richard Baron, MD, acknowledged that "ABIM clearly got it wrong. We launched programs that weren't ready and we didn't deliver an MOC program that physicians found meaningful."

Dr. Wachter, who was ABIM's chair when Dr. Baron was hired, says that ABIM's new plan to reach out to specialty societies means SHM can lobby for an MOC process that is more current, more applicable, and more meaningful to practitioners. Given that HM as a specialty was launched as a novel idea on what would make a good care model for hospitalized patients, Dr. Wachter is confident that SHM can be helpful in guiding the creation of a better MOC process.

Hospital medicine "was built on out-of-the-box thinking, on accepting certain parts of the old model of what a good doctor was but throwing other parts out and saying, 'We want to rethink this,'" Dr. Wachter says. "I can't think of a specialty that’s better positioned to help."

Meanwhile, hospitalist and ABIM Council member Jeff Wiese, MD, MHM, sees an opportunity to make sure the overall process for "knowledge improvement" is enhanced so that disconnects between practitioners and ABIM do not continue.

"We have to ensure that what happened over the past 20 years doesn't happen again," Dr. Wiese says. "Namely, that the world of medicine doesn't move so fast that the ABIM MOC requirements don't keep up. If we engage as physicians and specialty organizations in meaningful dialogues…then we have a much better chance of making MOC sufficiently dynamic to meet the changing times."

SHM President Burke Kealey, MD, SFHM, says that hospitalists were less impacted than some other specialists by the MOC change because they could use the Focused Practice in Hospital Medicine (FPHM) exam. The FPHM test was crafted by "real practicing hospitalists [writing] the questions for hospitalists from the point of view of what a hospitalist needs to know to do their job," he says.

Dr. Kealey adds that SHM plans to help hospitalists prepare for exams through courses featured at next month’s annual meeting and with the publication of a study guide due out this fall focused on the test's nonclinical aspects. Since it was posted last week, Dr. Kealey's blog on "The Hospital Leader" has attracted the interest of thousands of hospitalists and has been shared more than 70 times.

Visit our website for more information on Maintenance of Certification issues.

No association between an increased risk of acute pancreatitis and treatment with incretin therapy for type 2 diabetes was found in a large case control-study.

To evaluate whether the risk of acute pancreatitis was increased among patients treated with incretin-based drugs – glucagonlike peptide–1 (GLP-1) receptor agonists and dipeptidyl peptidase–4 (DPP-4) inhibitors – the investigators compared the risks of acute pancreatitis associated with different antihyperglycemic drugs in 12,868 people hospitalized for the first time for acute pancreatitis, and in 12,680 controls matched for birth year, sex, and region of residence in Denmark.

The study addressed evidence indicating that incretins may cause pancreatitis and pancreatic cancer in humans, which includes adverse event reports suggesting a signal of pancreatitis, but the association between incretins and acute pancreatitis is controversial and is an issue that “remains under debate,” they noted.

The data used were from three Danish databases, including one of reimbursed prescriptions. After adjustment for comorbidities and drugs associated with pancreatitis, including alcoholism and obesity, the risk of acute pancreatitis was not increased among those who had ever used an incretin, with an odds ratio of 0.95, according to Dr. Reimar Thomsen of the department of clinical epidemiology, Institute of Clinical Medicine, Aarhus (Denmark) University Hospital, and his associates (Diabetes Care 2015 [doi:10.2337/dc13-2983])

Risk was also not increased among those who had been ever treated with a DPP-4 inhibitor (OR, 1.04), which included an OR of 1.06 for sitagliptin, or among those who had been treated with a GLP-1 receptor agonist (OR, 0.82), which included an OR of 0.75 for liraglutide. Nor was risk elevated among those treated with nonincretin antihyperglycemic drugs (OR, 1.05).

In addition, the adjusted odds ratio comparing the risk of acute pancreatitis associated with incretin treatments and other antihyperglycemics was not increased, approaching 1.

The crude odds ratios, before adjustment for confounding factors, was 1.36 in patients who had been treated with incretins and 1.44 among those who had been treated with other antihyperglycemic drugs. “The fact that crude ORs were increased to very similar levels for all antihyperglycemic drugs – given their different modes of action – points to a general underlying diabetes effect on pancreatitis risk, rather than a specific drug effect,” they commented. In the crude analyses, they determined that obesity, gallstones, and other diabetes-related risk factors “may explain much of the apparent risk increase,” the investigators added.

Other findings included an increased risk of acute pancreatitis among those who had recently started treatment with a DPP-4 inhibitor and in those who had recently started treatment with several other antihyperglycemic drugs, including sulfonylureas and insulin. “This lack of specificity suggests that either the increased pancreatitis risk is related to newly diagnosed and drug-treated type 2 diabetes per se, with a possibility of reverse causality due to pancreatogenic diabetes,” or that starting therapy with sulfonylureas and insulin “also causes acute pancreatitis, which should be further investigated,” they said.

Incretin-based drugs include injectable incretin mimetic agents (GLP-1 receptor agonists) such as liraglutide; and incretin enhancers (DPP-4) inhibitors, such as sitagliptin.

The study was supported by the Clinical Epidemiological Research Foundation in Denmark. One of the authors, from the Danish Center for Strategic Research in Type 2 Diabetes, at Odense University Hospital, disclosed having received research grants form Novo-Nordisk. Of the six authors, four are from the Aarhus University Hospital clinical epidemiology department, a member of the center, which receives funding that includes an unrestricted donation from Novo-Nordisk.

[email protected]

No association between an increased risk of acute pancreatitis and treatment with incretin therapy for type 2 diabetes was found in a large case control-study.

To evaluate whether the risk of acute pancreatitis was increased among patients treated with incretin-based drugs – glucagonlike peptide–1 (GLP-1) receptor agonists and dipeptidyl peptidase–4 (DPP-4) inhibitors – the investigators compared the risks of acute pancreatitis associated with different antihyperglycemic drugs in 12,868 people hospitalized for the first time for acute pancreatitis, and in 12,680 controls matched for birth year, sex, and region of residence in Denmark.

The study addressed evidence indicating that incretins may cause pancreatitis and pancreatic cancer in humans, which includes adverse event reports suggesting a signal of pancreatitis, but the association between incretins and acute pancreatitis is controversial and is an issue that “remains under debate,” they noted.

The data used were from three Danish databases, including one of reimbursed prescriptions. After adjustment for comorbidities and drugs associated with pancreatitis, including alcoholism and obesity, the risk of acute pancreatitis was not increased among those who had ever used an incretin, with an odds ratio of 0.95, according to Dr. Reimar Thomsen of the department of clinical epidemiology, Institute of Clinical Medicine, Aarhus (Denmark) University Hospital, and his associates (Diabetes Care 2015 [doi:10.2337/dc13-2983])

Risk was also not increased among those who had been ever treated with a DPP-4 inhibitor (OR, 1.04), which included an OR of 1.06 for sitagliptin, or among those who had been treated with a GLP-1 receptor agonist (OR, 0.82), which included an OR of 0.75 for liraglutide. Nor was risk elevated among those treated with nonincretin antihyperglycemic drugs (OR, 1.05).

In addition, the adjusted odds ratio comparing the risk of acute pancreatitis associated with incretin treatments and other antihyperglycemics was not increased, approaching 1.

The crude odds ratios, before adjustment for confounding factors, was 1.36 in patients who had been treated with incretins and 1.44 among those who had been treated with other antihyperglycemic drugs. “The fact that crude ORs were increased to very similar levels for all antihyperglycemic drugs – given their different modes of action – points to a general underlying diabetes effect on pancreatitis risk, rather than a specific drug effect,” they commented. In the crude analyses, they determined that obesity, gallstones, and other diabetes-related risk factors “may explain much of the apparent risk increase,” the investigators added.

Other findings included an increased risk of acute pancreatitis among those who had recently started treatment with a DPP-4 inhibitor and in those who had recently started treatment with several other antihyperglycemic drugs, including sulfonylureas and insulin. “This lack of specificity suggests that either the increased pancreatitis risk is related to newly diagnosed and drug-treated type 2 diabetes per se, with a possibility of reverse causality due to pancreatogenic diabetes,” or that starting therapy with sulfonylureas and insulin “also causes acute pancreatitis, which should be further investigated,” they said.

Incretin-based drugs include injectable incretin mimetic agents (GLP-1 receptor agonists) such as liraglutide; and incretin enhancers (DPP-4) inhibitors, such as sitagliptin.

The study was supported by the Clinical Epidemiological Research Foundation in Denmark. One of the authors, from the Danish Center for Strategic Research in Type 2 Diabetes, at Odense University Hospital, disclosed having received research grants form Novo-Nordisk. Of the six authors, four are from the Aarhus University Hospital clinical epidemiology department, a member of the center, which receives funding that includes an unrestricted donation from Novo-Nordisk.

[email protected]

No association between an increased risk of acute pancreatitis and treatment with incretin therapy for type 2 diabetes was found in a large case control-study.

To evaluate whether the risk of acute pancreatitis was increased among patients treated with incretin-based drugs – glucagonlike peptide–1 (GLP-1) receptor agonists and dipeptidyl peptidase–4 (DPP-4) inhibitors – the investigators compared the risks of acute pancreatitis associated with different antihyperglycemic drugs in 12,868 people hospitalized for the first time for acute pancreatitis, and in 12,680 controls matched for birth year, sex, and region of residence in Denmark.

The study addressed evidence indicating that incretins may cause pancreatitis and pancreatic cancer in humans, which includes adverse event reports suggesting a signal of pancreatitis, but the association between incretins and acute pancreatitis is controversial and is an issue that “remains under debate,” they noted.

The data used were from three Danish databases, including one of reimbursed prescriptions. After adjustment for comorbidities and drugs associated with pancreatitis, including alcoholism and obesity, the risk of acute pancreatitis was not increased among those who had ever used an incretin, with an odds ratio of 0.95, according to Dr. Reimar Thomsen of the department of clinical epidemiology, Institute of Clinical Medicine, Aarhus (Denmark) University Hospital, and his associates (Diabetes Care 2015 [doi:10.2337/dc13-2983])

Risk was also not increased among those who had been ever treated with a DPP-4 inhibitor (OR, 1.04), which included an OR of 1.06 for sitagliptin, or among those who had been treated with a GLP-1 receptor agonist (OR, 0.82), which included an OR of 0.75 for liraglutide. Nor was risk elevated among those treated with nonincretin antihyperglycemic drugs (OR, 1.05).

In addition, the adjusted odds ratio comparing the risk of acute pancreatitis associated with incretin treatments and other antihyperglycemics was not increased, approaching 1.

The crude odds ratios, before adjustment for confounding factors, was 1.36 in patients who had been treated with incretins and 1.44 among those who had been treated with other antihyperglycemic drugs. “The fact that crude ORs were increased to very similar levels for all antihyperglycemic drugs – given their different modes of action – points to a general underlying diabetes effect on pancreatitis risk, rather than a specific drug effect,” they commented. In the crude analyses, they determined that obesity, gallstones, and other diabetes-related risk factors “may explain much of the apparent risk increase,” the investigators added.

Other findings included an increased risk of acute pancreatitis among those who had recently started treatment with a DPP-4 inhibitor and in those who had recently started treatment with several other antihyperglycemic drugs, including sulfonylureas and insulin. “This lack of specificity suggests that either the increased pancreatitis risk is related to newly diagnosed and drug-treated type 2 diabetes per se, with a possibility of reverse causality due to pancreatogenic diabetes,” or that starting therapy with sulfonylureas and insulin “also causes acute pancreatitis, which should be further investigated,” they said.

Incretin-based drugs include injectable incretin mimetic agents (GLP-1 receptor agonists) such as liraglutide; and incretin enhancers (DPP-4) inhibitors, such as sitagliptin.

The study was supported by the Clinical Epidemiological Research Foundation in Denmark. One of the authors, from the Danish Center for Strategic Research in Type 2 Diabetes, at Odense University Hospital, disclosed having received research grants form Novo-Nordisk. Of the six authors, four are from the Aarhus University Hospital clinical epidemiology department, a member of the center, which receives funding that includes an unrestricted donation from Novo-Nordisk.

[email protected]

Clinical question

Can a procalcitonin-based algorithm reduce antibiotic use in critically ill patients?

Bottom line

A procalcitonin-based algorithm using a 0.1 ng/mL cutoff does not significantly decrease the duration of antibiotic treatment in critically ill patients nor does it reduce length of stay or number of deaths. The rate of decline in the procalcitonin level over the first 72 hours, however, does serve as an independent predictor of short-term and long-term all-cause mortality. (LOE = 1b-)

Reference

Shehabi Y, Sterba M, Garrett PM, et al, for the ProGUARD Study Investigators and the ANZICS Clinical Trials Group. Procalcitonin algorithm in critically ill adults with undifferentiated infection or suspected sepsis. Am J Respir Crit Care Med 2014;190(10):1102-1110.

Study design: Randomized controlled trial (nonblinded)

Funding source: Foundation

Allocation: Concealed

Setting: Inpatient (ICU only)

Synopsis

Procalcitonin (PCT) is a sepsis biomarker that has been utilized to guide antibiotic use in different patient populations. In this study, the authors tested a PCT-algorithm using a 0.1 ng/mL cut-off to reduce antibiotic exposure in critically ill patients. Patients newly admitted to intensive care units (ICUs) who were receiving antibiotics for suspected infections were randomized, using concealed allocation, to receive PCT-guided care (n = 196) or standard care (n = 198). All patients had PCT levels drawn daily until discharge from the ICU or up to a maximum of 7 days. In the PCT group, antibiotics were stopped if PCT levels were negative (< 0.1 ng/mL), if PCT levels were borderline (0.1 - 0.25 ng/mL) and infection was unlikely, or if PCT levels decreased more than 90% from baseline values. In the standard care group, the treating clinician determined antibiotic use without knowledge of the PCT results. Baseline characteristics of the 2 groups were similar with regard to severity-of-disease scores and baseline PCT values. There was high compliance with the PCT algorithm, with less than 3% of study days when the algorithm was not followed. There was no significant difference detected between the 2 groups for the primary outcome of time to antibiotic cessation. However, duration of antibiotic use was longer than expected in the control group (11 days actual vs 9 days expected), so the study may have been underpowered to detect an expected 25% reduction. Nevertheless, the 2 groups were similar with regard to ICU and hospital lengths of stay, as well as ICU, hospital, and 90-day mortality rates. Of note, the rate of decline in PCT level over the first 72 hours was an independent predictor of hospital mortality and 90-day mortality, with a slower decline corresponding to a higher mortality.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

Can a procalcitonin-based algorithm reduce antibiotic use in critically ill patients?

Bottom line

A procalcitonin-based algorithm using a 0.1 ng/mL cutoff does not significantly decrease the duration of antibiotic treatment in critically ill patients nor does it reduce length of stay or number of deaths. The rate of decline in the procalcitonin level over the first 72 hours, however, does serve as an independent predictor of short-term and long-term all-cause mortality. (LOE = 1b-)

Reference

Shehabi Y, Sterba M, Garrett PM, et al, for the ProGUARD Study Investigators and the ANZICS Clinical Trials Group. Procalcitonin algorithm in critically ill adults with undifferentiated infection or suspected sepsis. Am J Respir Crit Care Med 2014;190(10):1102-1110.

Study design: Randomized controlled trial (nonblinded)

Funding source: Foundation

Allocation: Concealed

Setting: Inpatient (ICU only)

Synopsis

Procalcitonin (PCT) is a sepsis biomarker that has been utilized to guide antibiotic use in different patient populations. In this study, the authors tested a PCT-algorithm using a 0.1 ng/mL cut-off to reduce antibiotic exposure in critically ill patients. Patients newly admitted to intensive care units (ICUs) who were receiving antibiotics for suspected infections were randomized, using concealed allocation, to receive PCT-guided care (n = 196) or standard care (n = 198). All patients had PCT levels drawn daily until discharge from the ICU or up to a maximum of 7 days. In the PCT group, antibiotics were stopped if PCT levels were negative (< 0.1 ng/mL), if PCT levels were borderline (0.1 - 0.25 ng/mL) and infection was unlikely, or if PCT levels decreased more than 90% from baseline values. In the standard care group, the treating clinician determined antibiotic use without knowledge of the PCT results. Baseline characteristics of the 2 groups were similar with regard to severity-of-disease scores and baseline PCT values. There was high compliance with the PCT algorithm, with less than 3% of study days when the algorithm was not followed. There was no significant difference detected between the 2 groups for the primary outcome of time to antibiotic cessation. However, duration of antibiotic use was longer than expected in the control group (11 days actual vs 9 days expected), so the study may have been underpowered to detect an expected 25% reduction. Nevertheless, the 2 groups were similar with regard to ICU and hospital lengths of stay, as well as ICU, hospital, and 90-day mortality rates. Of note, the rate of decline in PCT level over the first 72 hours was an independent predictor of hospital mortality and 90-day mortality, with a slower decline corresponding to a higher mortality.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

Can a procalcitonin-based algorithm reduce antibiotic use in critically ill patients?

Bottom line

A procalcitonin-based algorithm using a 0.1 ng/mL cutoff does not significantly decrease the duration of antibiotic treatment in critically ill patients nor does it reduce length of stay or number of deaths. The rate of decline in the procalcitonin level over the first 72 hours, however, does serve as an independent predictor of short-term and long-term all-cause mortality. (LOE = 1b-)

Reference

Shehabi Y, Sterba M, Garrett PM, et al, for the ProGUARD Study Investigators and the ANZICS Clinical Trials Group. Procalcitonin algorithm in critically ill adults with undifferentiated infection or suspected sepsis. Am J Respir Crit Care Med 2014;190(10):1102-1110.

Study design: Randomized controlled trial (nonblinded)

Funding source: Foundation

Allocation: Concealed

Setting: Inpatient (ICU only)

Synopsis

Procalcitonin (PCT) is a sepsis biomarker that has been utilized to guide antibiotic use in different patient populations. In this study, the authors tested a PCT-algorithm using a 0.1 ng/mL cut-off to reduce antibiotic exposure in critically ill patients. Patients newly admitted to intensive care units (ICUs) who were receiving antibiotics for suspected infections were randomized, using concealed allocation, to receive PCT-guided care (n = 196) or standard care (n = 198). All patients had PCT levels drawn daily until discharge from the ICU or up to a maximum of 7 days. In the PCT group, antibiotics were stopped if PCT levels were negative (< 0.1 ng/mL), if PCT levels were borderline (0.1 - 0.25 ng/mL) and infection was unlikely, or if PCT levels decreased more than 90% from baseline values. In the standard care group, the treating clinician determined antibiotic use without knowledge of the PCT results. Baseline characteristics of the 2 groups were similar with regard to severity-of-disease scores and baseline PCT values. There was high compliance with the PCT algorithm, with less than 3% of study days when the algorithm was not followed. There was no significant difference detected between the 2 groups for the primary outcome of time to antibiotic cessation. However, duration of antibiotic use was longer than expected in the control group (11 days actual vs 9 days expected), so the study may have been underpowered to detect an expected 25% reduction. Nevertheless, the 2 groups were similar with regard to ICU and hospital lengths of stay, as well as ICU, hospital, and 90-day mortality rates. Of note, the rate of decline in PCT level over the first 72 hours was an independent predictor of hospital mortality and 90-day mortality, with a slower decline corresponding to a higher mortality.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

Does early nasoenteric feeding decrease the rate of infections or death in patients hospitalized with severe acute pancreatitis?

Bottom line

In patients with severe acute pancreatitis, early nasoenteric feeding initiated within 24 hours of presentation, as compared with oral feeding after 72 hours, does not improve mortality or reduce the rate of major infections. (LOE = 1b-)

Reference

Bakker OJ, van Brunschot S, van Santvoort HC, et al, for the Dutch Pancreatitis Study Group. Early versus on-demand nasoenteric tube feeding in acute pancreatitis. N Engl J Med 2014;371(21):1983-1993.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (ward only)

Synopsis

Previous observational studies suggest that early nasoenteric feeding in patients with acute pancreatitis may reduce the rate of major infections by stimulating intestinal motility, reducing bacterial overgrowth, and increasing splanchnic blood flow. Using concealed allocation, these authors randomized patients presenting to the emergency department with severe acute pancreatitis to receive either early nasoenteric tube feeding initiated within 24 hours (n = 102) or oral feeding started at 72 hours (n = 106). If the oral diet was not tolerated, tube feeding was initiated after 96 hours. The 2 groups were similar at baseline: the mean age was 65 years and 60% of the patients had evidence of systemic inflammatory response syndrome (SIRS). Analysis was by intention to treat. One third of patients in the oral group eventually required tube feeding. For the primary composite end point of death or major infection (infected pancreatic necrosis, bacteremia, or pneumonia), there was no significant difference detected between the 2 groups. When the outcomes of major infection and death were examined separately, the 2 groups again had comparable results. Finally, patients in both groups had similar rates of admission to the intensive care unit and similar need for mechanical ventilation. Given fewer-than-expected events in the control group, it is possible that the study was too small to detect a difference in the primary outcome, if such a difference exists.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

Does early nasoenteric feeding decrease the rate of infections or death in patients hospitalized with severe acute pancreatitis?

Bottom line

In patients with severe acute pancreatitis, early nasoenteric feeding initiated within 24 hours of presentation, as compared with oral feeding after 72 hours, does not improve mortality or reduce the rate of major infections. (LOE = 1b-)

Reference

Bakker OJ, van Brunschot S, van Santvoort HC, et al, for the Dutch Pancreatitis Study Group. Early versus on-demand nasoenteric tube feeding in acute pancreatitis. N Engl J Med 2014;371(21):1983-1993.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (ward only)

Synopsis

Previous observational studies suggest that early nasoenteric feeding in patients with acute pancreatitis may reduce the rate of major infections by stimulating intestinal motility, reducing bacterial overgrowth, and increasing splanchnic blood flow. Using concealed allocation, these authors randomized patients presenting to the emergency department with severe acute pancreatitis to receive either early nasoenteric tube feeding initiated within 24 hours (n = 102) or oral feeding started at 72 hours (n = 106). If the oral diet was not tolerated, tube feeding was initiated after 96 hours. The 2 groups were similar at baseline: the mean age was 65 years and 60% of the patients had evidence of systemic inflammatory response syndrome (SIRS). Analysis was by intention to treat. One third of patients in the oral group eventually required tube feeding. For the primary composite end point of death or major infection (infected pancreatic necrosis, bacteremia, or pneumonia), there was no significant difference detected between the 2 groups. When the outcomes of major infection and death were examined separately, the 2 groups again had comparable results. Finally, patients in both groups had similar rates of admission to the intensive care unit and similar need for mechanical ventilation. Given fewer-than-expected events in the control group, it is possible that the study was too small to detect a difference in the primary outcome, if such a difference exists.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

Does early nasoenteric feeding decrease the rate of infections or death in patients hospitalized with severe acute pancreatitis?

Bottom line

In patients with severe acute pancreatitis, early nasoenteric feeding initiated within 24 hours of presentation, as compared with oral feeding after 72 hours, does not improve mortality or reduce the rate of major infections. (LOE = 1b-)

Reference

Bakker OJ, van Brunschot S, van Santvoort HC, et al, for the Dutch Pancreatitis Study Group. Early versus on-demand nasoenteric tube feeding in acute pancreatitis. N Engl J Med 2014;371(21):1983-1993.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (ward only)

Synopsis

Previous observational studies suggest that early nasoenteric feeding in patients with acute pancreatitis may reduce the rate of major infections by stimulating intestinal motility, reducing bacterial overgrowth, and increasing splanchnic blood flow. Using concealed allocation, these authors randomized patients presenting to the emergency department with severe acute pancreatitis to receive either early nasoenteric tube feeding initiated within 24 hours (n = 102) or oral feeding started at 72 hours (n = 106). If the oral diet was not tolerated, tube feeding was initiated after 96 hours. The 2 groups were similar at baseline: the mean age was 65 years and 60% of the patients had evidence of systemic inflammatory response syndrome (SIRS). Analysis was by intention to treat. One third of patients in the oral group eventually required tube feeding. For the primary composite end point of death or major infection (infected pancreatic necrosis, bacteremia, or pneumonia), there was no significant difference detected between the 2 groups. When the outcomes of major infection and death were examined separately, the 2 groups again had comparable results. Finally, patients in both groups had similar rates of admission to the intensive care unit and similar need for mechanical ventilation. Given fewer-than-expected events in the control group, it is possible that the study was too small to detect a difference in the primary outcome, if such a difference exists.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

I say “Thank you” a lot to patients. And I mean it.

I like being a doctor. It’s something I always wanted to do. For all the difficulties that go along with it, I still enjoy the actual job of caring for those who come to me. They’re the reason I’m here, and they keep my practice afloat and let me do what I want in life.

Like any other business, I have competitors. In my area, people have a choice of neurologists, and I appreciate that they picked me. So I always try to thank them when walking up to checkout.

A big part of what makes the job rewarding are those who feel the same way about me. It’s always nice when they thank me for helping, or trying to help, or just listening. I try to be a good doctor, so I’m glad to have someone recognize that. In this field, you can’t make everyone happy, but if I can have a solid majority who understand that I’m doing my best for them, I’ll take it.

I’m not fishing for compliments, or gifts, or a parade. Experience has taught me that patients who are overly flattering are most likely not to mean it. If someone calls me too many wonderful things, I immediately worry about their ulterior motives. Are they looking for narcotics? Disability? A legal action?

But a simple, sincere, “Thank you” from a patient can make it all worthwhile. Even on a bad day, it’s still a bright spot. It’s nice to know I’m making a difference. When I get a small note or appreciative Christmas card from a patient, I save it. They go in a drawer to be taken out and read after a particularly rough time, to remind myself that I must be doing something right.

Being appreciated reminds me why I’m here, and that this was the right choice for me. It lets me know that I’m doing what I set out to do many years ago: to help people.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I say “Thank you” a lot to patients. And I mean it.

I like being a doctor. It’s something I always wanted to do. For all the difficulties that go along with it, I still enjoy the actual job of caring for those who come to me. They’re the reason I’m here, and they keep my practice afloat and let me do what I want in life.

Like any other business, I have competitors. In my area, people have a choice of neurologists, and I appreciate that they picked me. So I always try to thank them when walking up to checkout.

A big part of what makes the job rewarding are those who feel the same way about me. It’s always nice when they thank me for helping, or trying to help, or just listening. I try to be a good doctor, so I’m glad to have someone recognize that. In this field, you can’t make everyone happy, but if I can have a solid majority who understand that I’m doing my best for them, I’ll take it.

I’m not fishing for compliments, or gifts, or a parade. Experience has taught me that patients who are overly flattering are most likely not to mean it. If someone calls me too many wonderful things, I immediately worry about their ulterior motives. Are they looking for narcotics? Disability? A legal action?

But a simple, sincere, “Thank you” from a patient can make it all worthwhile. Even on a bad day, it’s still a bright spot. It’s nice to know I’m making a difference. When I get a small note or appreciative Christmas card from a patient, I save it. They go in a drawer to be taken out and read after a particularly rough time, to remind myself that I must be doing something right.

Being appreciated reminds me why I’m here, and that this was the right choice for me. It lets me know that I’m doing what I set out to do many years ago: to help people.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I say “Thank you” a lot to patients. And I mean it.

I like being a doctor. It’s something I always wanted to do. For all the difficulties that go along with it, I still enjoy the actual job of caring for those who come to me. They’re the reason I’m here, and they keep my practice afloat and let me do what I want in life.

Like any other business, I have competitors. In my area, people have a choice of neurologists, and I appreciate that they picked me. So I always try to thank them when walking up to checkout.

A big part of what makes the job rewarding are those who feel the same way about me. It’s always nice when they thank me for helping, or trying to help, or just listening. I try to be a good doctor, so I’m glad to have someone recognize that. In this field, you can’t make everyone happy, but if I can have a solid majority who understand that I’m doing my best for them, I’ll take it.

I’m not fishing for compliments, or gifts, or a parade. Experience has taught me that patients who are overly flattering are most likely not to mean it. If someone calls me too many wonderful things, I immediately worry about their ulterior motives. Are they looking for narcotics? Disability? A legal action?

But a simple, sincere, “Thank you” from a patient can make it all worthwhile. Even on a bad day, it’s still a bright spot. It’s nice to know I’m making a difference. When I get a small note or appreciative Christmas card from a patient, I save it. They go in a drawer to be taken out and read after a particularly rough time, to remind myself that I must be doing something right.

Being appreciated reminds me why I’m here, and that this was the right choice for me. It lets me know that I’m doing what I set out to do many years ago: to help people.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Bertie Gottgens, PhD

Photo courtesy of

University of Cambridge

A new computer model that simulates blood cell development could aid the discovery of novel treatments for hematologic malignancies, according to researchers.

“With this new computer model, we can carry out simulated experiments in seconds that would take many weeks to perform in the laboratory, dramatically speeding up research into blood development and the genetic mutations that cause leukemia,” said Bertie Gottgens, PhD, of the University of Cambridge in the UK.

Dr Gottgens and his colleagues explained this research in Nature Biotechnology.

To start, the researchers measured the activity of 48 genes in 3934 hematopoietic progenitor cells. They used the resulting dataset to construct the computer model of blood cell development, using computational approaches originally developed at Microsoft Research for the synthesis of computer code.

Subsequent lab experiments validated the accuracy of the model.

The researchers noted that the model can be used to simulate the activity of key genes implicated in hematologic malignancies. For example, around 1 in 5 children who develop leukemia have a faulty version of the RUNX1 gene, as do a similar proportion of adults with acute myeloid leukemia.

The computer model shows how RUNX1 interacts with other genes to control blood cell development. The gene produces the RUNX1 protein, which, in healthy patients, activates a network of key genes. In leukemia patients, an altered form of the protein is thought to suppress the network.

If the researchers change the “rules” in the network model, they can simulate the formation of abnormal leukemia cells. By tweaking the leukemia model until the behavior of the network reverts back to normal, the team can identify pathways that, potentially, could be targeted with drugs.

“Because the computer simulations are very fast, we can quickly screen through lots of possibilities to pick the most promising ones as pathways for drug development,” Dr Gottgens said.

“The cost of developing a new drug is enormous, and much of this cost comes from new candidate drugs failing late in the drug development process. Our model could significantly reduce the risk of failure, with the potential to make drug discovery faster and cheaper.”

Bertie Gottgens, PhD

Photo courtesy of

University of Cambridge

A new computer model that simulates blood cell development could aid the discovery of novel treatments for hematologic malignancies, according to researchers.

“With this new computer model, we can carry out simulated experiments in seconds that would take many weeks to perform in the laboratory, dramatically speeding up research into blood development and the genetic mutations that cause leukemia,” said Bertie Gottgens, PhD, of the University of Cambridge in the UK.

Dr Gottgens and his colleagues explained this research in Nature Biotechnology.

To start, the researchers measured the activity of 48 genes in 3934 hematopoietic progenitor cells. They used the resulting dataset to construct the computer model of blood cell development, using computational approaches originally developed at Microsoft Research for the synthesis of computer code.

Subsequent lab experiments validated the accuracy of the model.

The researchers noted that the model can be used to simulate the activity of key genes implicated in hematologic malignancies. For example, around 1 in 5 children who develop leukemia have a faulty version of the RUNX1 gene, as do a similar proportion of adults with acute myeloid leukemia.

The computer model shows how RUNX1 interacts with other genes to control blood cell development. The gene produces the RUNX1 protein, which, in healthy patients, activates a network of key genes. In leukemia patients, an altered form of the protein is thought to suppress the network.

If the researchers change the “rules” in the network model, they can simulate the formation of abnormal leukemia cells. By tweaking the leukemia model until the behavior of the network reverts back to normal, the team can identify pathways that, potentially, could be targeted with drugs.

“Because the computer simulations are very fast, we can quickly screen through lots of possibilities to pick the most promising ones as pathways for drug development,” Dr Gottgens said.

“The cost of developing a new drug is enormous, and much of this cost comes from new candidate drugs failing late in the drug development process. Our model could significantly reduce the risk of failure, with the potential to make drug discovery faster and cheaper.”

Bertie Gottgens, PhD

Photo courtesy of

University of Cambridge

A new computer model that simulates blood cell development could aid the discovery of novel treatments for hematologic malignancies, according to researchers.

“With this new computer model, we can carry out simulated experiments in seconds that would take many weeks to perform in the laboratory, dramatically speeding up research into blood development and the genetic mutations that cause leukemia,” said Bertie Gottgens, PhD, of the University of Cambridge in the UK.

Dr Gottgens and his colleagues explained this research in Nature Biotechnology.

To start, the researchers measured the activity of 48 genes in 3934 hematopoietic progenitor cells. They used the resulting dataset to construct the computer model of blood cell development, using computational approaches originally developed at Microsoft Research for the synthesis of computer code.

Subsequent lab experiments validated the accuracy of the model.

The researchers noted that the model can be used to simulate the activity of key genes implicated in hematologic malignancies. For example, around 1 in 5 children who develop leukemia have a faulty version of the RUNX1 gene, as do a similar proportion of adults with acute myeloid leukemia.

The computer model shows how RUNX1 interacts with other genes to control blood cell development. The gene produces the RUNX1 protein, which, in healthy patients, activates a network of key genes. In leukemia patients, an altered form of the protein is thought to suppress the network.

If the researchers change the “rules” in the network model, they can simulate the formation of abnormal leukemia cells. By tweaking the leukemia model until the behavior of the network reverts back to normal, the team can identify pathways that, potentially, could be targeted with drugs.

“Because the computer simulations are very fast, we can quickly screen through lots of possibilities to pick the most promising ones as pathways for drug development,” Dr Gottgens said.

“The cost of developing a new drug is enormous, and much of this cost comes from new candidate drugs failing late in the drug development process. Our model could significantly reduce the risk of failure, with the potential to make drug discovery faster and cheaper.”

Bertrand Coiffier, MD, PhD

Photo by Larry Young

SAN FRANCISCO—Adding romidepsin to CHOP can enhance the regimen’s efficacy against peripheral T-cell lymphoma (PTCL), but the combination can also induce severe toxicity, results of a phase 1b/2 study have shown.

In patients with previously untreated PTCL, romidepsin plus CHOP elicited an overall response rate of about 69%.

But all patients experienced adverse events, a median of 49 per patient. In addition, rates of hematologic toxicities were high, and 3 patients experienced acute cardiac toxicity.

Bertrand Coiffier, MD, PhD, of CHU Lyon Sud in Pierre Benite, France, presented these findings at the 7th Annual T-cell Lymphoma Forum. Dr Coiffier and other researchers involved in this study receive funds from Celgene, the company developing romidepsin.

“CHOP is widely accepted,” Dr Coiffier noted. “It’s the most-used regimen for peripheral T-cell lymphoma, but it’s not the best one, and we certainly have regimens that do produce more [complete responses] and longer responses.”

He said researchers decided to test romidepsin in combination with CHOP because studies have suggested that romidepsin has very good efficacy in relapsed/refractory peripheral T-cell lymphoma, and the toxicities associated with romidepsin and CHOP alone have been managable.

So the researchers tested the combination in 37 patients with untreated PTCL, most of whom were male (n=20). The median age was 57, and 37.8% were older than 60. About 95% of patients had stage III/IV disease, and about 89% had an ECOG performance status less than 2.

Most patients had angioimmunoblastic T-cell lymphoma (n=17), followed by PTCL not otherwise specified (n=13), ALK- anaplastic large-cell lymphoma (n=3), enteropathy-associated T-cell lymphoma (n=1), hepatosplenic T-cell lymphoma (n=1), primary cutaneous CD4⁺ small/medium T-cell lymphoma (n=1), and “other” (n=1).

Early DLTs

The researchers used a standard “3+3” dose-escalation scheme, starting with a romidepsin dose of 10 mg/m² given on days 1 and 8.

In the first 2 cycles, there were 3 dose-limiting toxicities (DLTs)—1 case  of grade 3 syncope, 1 case of grade 3 general status alteration, and 1 case of grade 3 hematologic toxicity (neutropenia and thrombocytopenia) lasting longer than 7 days.

“So we looked at the definition of the criteria for DLT, and we thought that, this time, they were too severe,” Dr Coiffier said. “After a lot of discussion between all the investigators, we decided to modify the criteria for DLT regarding neutropenia or thrombocytopenia and to allow a little more toxicity before saying it’s a DLT.”

A DLT was initially defined as grade 3/4 non-hematologic toxicity, grade 3 hematologic toxicity lasting more than 7 days, or grade 4 hematologic toxicity lasting more than 3 days. The researchers modified the criteria so that hematologic toxicities would not be considered DLTs if they lasted less than 10 days for grade 3 or less than 7 days for grade 4.

When the team decreased the romidepsin dose to 8 mg/m², they did not observe any DLTs according to the new criteria. The same was true when they raised the dose back up to 10 mg/m².

There were, however, DLTs when the dose was increased to 12 mg/m². In cohort 5, there was a case of grade 3 cardiac failure, and in cohort 6, there were 2 cases of grade 3 nausea.

Nevertheless, 12 mg/m² became the phase 2 dose. In all, 25 patients received romidepsin at that dose.

Safety data

Twenty-six of 37 patients completed the 8 planned cycles of treatment. Five patients discontinued treatment due to progression and 6 due to toxicity (5 due to thrombocytopenia).

“One hundred percent of patients experienced at least one adverse event, but most of them were grade 1 or 2 [84%] and occurred during the first 2 cycles [38%],” Dr Coiffier said. “There were no deaths related to adverse events.”

Severe toxicities occurred during the expansion phase. There was a case of severe peripheral sensory neuropathy that led to treatment discontinuation, and there were 3 cases of acute cardiac toxicity. They all occurred after the first cycle, and none were fatal.

The rate of hematologic toxicity was high. Neutropenia occurred in all patients, thrombocytopenia in 94%, and anemia in 89%.

Grade 3/4 adverse events included neutropenia (85%), thrombocytopenia (35%), febrile neutropenia (19%), general status deterioration (13%), nausea/vomiting (10%), anemia (8%), hypophosphatemia (8%), fatigue (5%), mucositis (5%), decreased appetite (5%), hypocalcemia (3%), hyponatremia (3%), hypokalemia (3%), hypomagnesemia (3%), dysgeusia (3%), and peripheral sensory neuropathy (3%).

Response, survival, and next steps

About 51% of patients (18/35) achieved a complete response, and 17% (n=6) had a partial response. Twenty-six percent of patients (n=9) progressed.

The median follow-up was 30 months. The estimated 1-year progression-free survival was 57%, and the estimated 1-year overall survival was 82%.

“The [overall survival] curve is certainly much better than you would expect with just standard CHOP,” Dr Coiffier noted.

He added that this research has progressed to a phase 3 study comparing romidepsin and CHOP in combination to CHOP alone. There are 7 countries participating (France, Belgium, South Korea, Spain, Italy, Germany, and Portugal), and 100 patients have been enrolled thus far.

Bertrand Coiffier, MD, PhD

Photo by Larry Young

SAN FRANCISCO—Adding romidepsin to CHOP can enhance the regimen’s efficacy against peripheral T-cell lymphoma (PTCL), but the combination can also induce severe toxicity, results of a phase 1b/2 study have shown.

In patients with previously untreated PTCL, romidepsin plus CHOP elicited an overall response rate of about 69%.

But all patients experienced adverse events, a median of 49 per patient. In addition, rates of hematologic toxicities were high, and 3 patients experienced acute cardiac toxicity.

Bertrand Coiffier, MD, PhD, of CHU Lyon Sud in Pierre Benite, France, presented these findings at the 7th Annual T-cell Lymphoma Forum. Dr Coiffier and other researchers involved in this study receive funds from Celgene, the company developing romidepsin.

“CHOP is widely accepted,” Dr Coiffier noted. “It’s the most-used regimen for peripheral T-cell lymphoma, but it’s not the best one, and we certainly have regimens that do produce more [complete responses] and longer responses.”

He said researchers decided to test romidepsin in combination with CHOP because studies have suggested that romidepsin has very good efficacy in relapsed/refractory peripheral T-cell lymphoma, and the toxicities associated with romidepsin and CHOP alone have been managable.

So the researchers tested the combination in 37 patients with untreated PTCL, most of whom were male (n=20). The median age was 57, and 37.8% were older than 60. About 95% of patients had stage III/IV disease, and about 89% had an ECOG performance status less than 2.

Most patients had angioimmunoblastic T-cell lymphoma (n=17), followed by PTCL not otherwise specified (n=13), ALK- anaplastic large-cell lymphoma (n=3), enteropathy-associated T-cell lymphoma (n=1), hepatosplenic T-cell lymphoma (n=1), primary cutaneous CD4⁺ small/medium T-cell lymphoma (n=1), and “other” (n=1).

Early DLTs

The researchers used a standard “3+3” dose-escalation scheme, starting with a romidepsin dose of 10 mg/m² given on days 1 and 8.

In the first 2 cycles, there were 3 dose-limiting toxicities (DLTs)—1 case  of grade 3 syncope, 1 case of grade 3 general status alteration, and 1 case of grade 3 hematologic toxicity (neutropenia and thrombocytopenia) lasting longer than 7 days.

“So we looked at the definition of the criteria for DLT, and we thought that, this time, they were too severe,” Dr Coiffier said. “After a lot of discussion between all the investigators, we decided to modify the criteria for DLT regarding neutropenia or thrombocytopenia and to allow a little more toxicity before saying it’s a DLT.”

A DLT was initially defined as grade 3/4 non-hematologic toxicity, grade 3 hematologic toxicity lasting more than 7 days, or grade 4 hematologic toxicity lasting more than 3 days. The researchers modified the criteria so that hematologic toxicities would not be considered DLTs if they lasted less than 10 days for grade 3 or less than 7 days for grade 4.

When the team decreased the romidepsin dose to 8 mg/m², they did not observe any DLTs according to the new criteria. The same was true when they raised the dose back up to 10 mg/m².

There were, however, DLTs when the dose was increased to 12 mg/m². In cohort 5, there was a case of grade 3 cardiac failure, and in cohort 6, there were 2 cases of grade 3 nausea.

Nevertheless, 12 mg/m² became the phase 2 dose. In all, 25 patients received romidepsin at that dose.

Safety data

Twenty-six of 37 patients completed the 8 planned cycles of treatment. Five patients discontinued treatment due to progression and 6 due to toxicity (5 due to thrombocytopenia).

“One hundred percent of patients experienced at least one adverse event, but most of them were grade 1 or 2 [84%] and occurred during the first 2 cycles [38%],” Dr Coiffier said. “There were no deaths related to adverse events.”

Severe toxicities occurred during the expansion phase. There was a case of severe peripheral sensory neuropathy that led to treatment discontinuation, and there were 3 cases of acute cardiac toxicity. They all occurred after the first cycle, and none were fatal.

The rate of hematologic toxicity was high. Neutropenia occurred in all patients, thrombocytopenia in 94%, and anemia in 89%.

Grade 3/4 adverse events included neutropenia (85%), thrombocytopenia (35%), febrile neutropenia (19%), general status deterioration (13%), nausea/vomiting (10%), anemia (8%), hypophosphatemia (8%), fatigue (5%), mucositis (5%), decreased appetite (5%), hypocalcemia (3%), hyponatremia (3%), hypokalemia (3%), hypomagnesemia (3%), dysgeusia (3%), and peripheral sensory neuropathy (3%).

Response, survival, and next steps

About 51% of patients (18/35) achieved a complete response, and 17% (n=6) had a partial response. Twenty-six percent of patients (n=9) progressed.

The median follow-up was 30 months. The estimated 1-year progression-free survival was 57%, and the estimated 1-year overall survival was 82%.

“The [overall survival] curve is certainly much better than you would expect with just standard CHOP,” Dr Coiffier noted.

He added that this research has progressed to a phase 3 study comparing romidepsin and CHOP in combination to CHOP alone. There are 7 countries participating (France, Belgium, South Korea, Spain, Italy, Germany, and Portugal), and 100 patients have been enrolled thus far.

Bertrand Coiffier, MD, PhD

Photo by Larry Young

SAN FRANCISCO—Adding romidepsin to CHOP can enhance the regimen’s efficacy against peripheral T-cell lymphoma (PTCL), but the combination can also induce severe toxicity, results of a phase 1b/2 study have shown.

In patients with previously untreated PTCL, romidepsin plus CHOP elicited an overall response rate of about 69%.

But all patients experienced adverse events, a median of 49 per patient. In addition, rates of hematologic toxicities were high, and 3 patients experienced acute cardiac toxicity.

Bertrand Coiffier, MD, PhD, of CHU Lyon Sud in Pierre Benite, France, presented these findings at the 7th Annual T-cell Lymphoma Forum. Dr Coiffier and other researchers involved in this study receive funds from Celgene, the company developing romidepsin.

“CHOP is widely accepted,” Dr Coiffier noted. “It’s the most-used regimen for peripheral T-cell lymphoma, but it’s not the best one, and we certainly have regimens that do produce more [complete responses] and longer responses.”

He said researchers decided to test romidepsin in combination with CHOP because studies have suggested that romidepsin has very good efficacy in relapsed/refractory peripheral T-cell lymphoma, and the toxicities associated with romidepsin and CHOP alone have been managable.

So the researchers tested the combination in 37 patients with untreated PTCL, most of whom were male (n=20). The median age was 57, and 37.8% were older than 60. About 95% of patients had stage III/IV disease, and about 89% had an ECOG performance status less than 2.

Most patients had angioimmunoblastic T-cell lymphoma (n=17), followed by PTCL not otherwise specified (n=13), ALK- anaplastic large-cell lymphoma (n=3), enteropathy-associated T-cell lymphoma (n=1), hepatosplenic T-cell lymphoma (n=1), primary cutaneous CD4⁺ small/medium T-cell lymphoma (n=1), and “other” (n=1).

Early DLTs

The researchers used a standard “3+3” dose-escalation scheme, starting with a romidepsin dose of 10 mg/m² given on days 1 and 8.

In the first 2 cycles, there were 3 dose-limiting toxicities (DLTs)—1 case  of grade 3 syncope, 1 case of grade 3 general status alteration, and 1 case of grade 3 hematologic toxicity (neutropenia and thrombocytopenia) lasting longer than 7 days.

“So we looked at the definition of the criteria for DLT, and we thought that, this time, they were too severe,” Dr Coiffier said. “After a lot of discussion between all the investigators, we decided to modify the criteria for DLT regarding neutropenia or thrombocytopenia and to allow a little more toxicity before saying it’s a DLT.”

A DLT was initially defined as grade 3/4 non-hematologic toxicity, grade 3 hematologic toxicity lasting more than 7 days, or grade 4 hematologic toxicity lasting more than 3 days. The researchers modified the criteria so that hematologic toxicities would not be considered DLTs if they lasted less than 10 days for grade 3 or less than 7 days for grade 4.

When the team decreased the romidepsin dose to 8 mg/m², they did not observe any DLTs according to the new criteria. The same was true when they raised the dose back up to 10 mg/m².

There were, however, DLTs when the dose was increased to 12 mg/m². In cohort 5, there was a case of grade 3 cardiac failure, and in cohort 6, there were 2 cases of grade 3 nausea.

Nevertheless, 12 mg/m² became the phase 2 dose. In all, 25 patients received romidepsin at that dose.

Safety data

Twenty-six of 37 patients completed the 8 planned cycles of treatment. Five patients discontinued treatment due to progression and 6 due to toxicity (5 due to thrombocytopenia).

“One hundred percent of patients experienced at least one adverse event, but most of them were grade 1 or 2 [84%] and occurred during the first 2 cycles [38%],” Dr Coiffier said. “There were no deaths related to adverse events.”

Severe toxicities occurred during the expansion phase. There was a case of severe peripheral sensory neuropathy that led to treatment discontinuation, and there were 3 cases of acute cardiac toxicity. They all occurred after the first cycle, and none were fatal.

The rate of hematologic toxicity was high. Neutropenia occurred in all patients, thrombocytopenia in 94%, and anemia in 89%.

Grade 3/4 adverse events included neutropenia (85%), thrombocytopenia (35%), febrile neutropenia (19%), general status deterioration (13%), nausea/vomiting (10%), anemia (8%), hypophosphatemia (8%), fatigue (5%), mucositis (5%), decreased appetite (5%), hypocalcemia (3%), hyponatremia (3%), hypokalemia (3%), hypomagnesemia (3%), dysgeusia (3%), and peripheral sensory neuropathy (3%).

Response, survival, and next steps

About 51% of patients (18/35) achieved a complete response, and 17% (n=6) had a partial response. Twenty-six percent of patients (n=9) progressed.

The median follow-up was 30 months. The estimated 1-year progression-free survival was 57%, and the estimated 1-year overall survival was 82%.

“The [overall survival] curve is certainly much better than you would expect with just standard CHOP,” Dr Coiffier noted.

He added that this research has progressed to a phase 3 study comparing romidepsin and CHOP in combination to CHOP alone. There are 7 countries participating (France, Belgium, South Korea, Spain, Italy, Germany, and Portugal), and 100 patients have been enrolled thus far.

Patient consults with pharmacist

Photo by Rhoda Baer

The oral factor Xa inhibitor edoxaban (Savaysa) is now available in US pharmacies, according to Daiichi Sankyo Company, Limited, the company developing the drug.

Savaysa is approved by the US Food and Drug Administration to reduce the risk of stroke and systemic embolism (SE) in patients with non-valvular atrial fibrillation (NVAF), as well as for the treatment of deep vein thrombosis and pulmonary embolism following 5 to 10 days of initial therapy with a parenteral anticoagulant.

According to Savaysa’s label, it should not be used in NVAF patients with creatinine clearance levels greater than 95 mL/min because, in that population, there is an increased risk of ischemic stroke with the drug compared to warfarin.

Daiichi Sankyo has developed resources for physicians and patients to help ensure patients can begin and/or remain on Savaysa per physician instructions.

The Savaysa Savings Plus program will include a reimbursement hotline to assist patients and prescribers who request help understanding a patient’s available coverage. Eligible patients who are prescribed Savaysa can enroll in a copay savings program and pay $4 per month through the Savaysa Savings Card.

Vouchers will also be available to provide patients and doctors with a way to try Savaysa at no cost to see if it is right for the patient.

In addition, the Savaysa Patient Assistance Program will offer assistance to qualified individuals, providing free product to eligible patients who are prescribed Savaysa, are uninsured, and are unable to identify alternative payment sources.

The approval of Savaysa in the US is based on data from the ENGAGE AF-TIMI 48 trial and the Hokusai-VTE trial.

Patient consults with pharmacist

Photo by Rhoda Baer

The oral factor Xa inhibitor edoxaban (Savaysa) is now available in US pharmacies, according to Daiichi Sankyo Company, Limited, the company developing the drug.

Savaysa is approved by the US Food and Drug Administration to reduce the risk of stroke and systemic embolism (SE) in patients with non-valvular atrial fibrillation (NVAF), as well as for the treatment of deep vein thrombosis and pulmonary embolism following 5 to 10 days of initial therapy with a parenteral anticoagulant.

According to Savaysa’s label, it should not be used in NVAF patients with creatinine clearance levels greater than 95 mL/min because, in that population, there is an increased risk of ischemic stroke with the drug compared to warfarin.

Daiichi Sankyo has developed resources for physicians and patients to help ensure patients can begin and/or remain on Savaysa per physician instructions.

The Savaysa Savings Plus program will include a reimbursement hotline to assist patients and prescribers who request help understanding a patient’s available coverage. Eligible patients who are prescribed Savaysa can enroll in a copay savings program and pay $4 per month through the Savaysa Savings Card.

Vouchers will also be available to provide patients and doctors with a way to try Savaysa at no cost to see if it is right for the patient.

In addition, the Savaysa Patient Assistance Program will offer assistance to qualified individuals, providing free product to eligible patients who are prescribed Savaysa, are uninsured, and are unable to identify alternative payment sources.

The approval of Savaysa in the US is based on data from the ENGAGE AF-TIMI 48 trial and the Hokusai-VTE trial.

Patient consults with pharmacist

Photo by Rhoda Baer

The oral factor Xa inhibitor edoxaban (Savaysa) is now available in US pharmacies, according to Daiichi Sankyo Company, Limited, the company developing the drug.

Savaysa is approved by the US Food and Drug Administration to reduce the risk of stroke and systemic embolism (SE) in patients with non-valvular atrial fibrillation (NVAF), as well as for the treatment of deep vein thrombosis and pulmonary embolism following 5 to 10 days of initial therapy with a parenteral anticoagulant.

According to Savaysa’s label, it should not be used in NVAF patients with creatinine clearance levels greater than 95 mL/min because, in that population, there is an increased risk of ischemic stroke with the drug compared to warfarin.

Daiichi Sankyo has developed resources for physicians and patients to help ensure patients can begin and/or remain on Savaysa per physician instructions.

The Savaysa Savings Plus program will include a reimbursement hotline to assist patients and prescribers who request help understanding a patient’s available coverage. Eligible patients who are prescribed Savaysa can enroll in a copay savings program and pay $4 per month through the Savaysa Savings Card.

Vouchers will also be available to provide patients and doctors with a way to try Savaysa at no cost to see if it is right for the patient.

In addition, the Savaysa Patient Assistance Program will offer assistance to qualified individuals, providing free product to eligible patients who are prescribed Savaysa, are uninsured, and are unable to identify alternative payment sources.

The approval of Savaysa in the US is based on data from the ENGAGE AF-TIMI 48 trial and the Hokusai-VTE trial.

The blood-draw device

Photo courtesy of

Velano Vascular

The US Food and Drug Administration (FDA) has cleared for marketing a device that reduces the need for venipunctures for in-hospital blood draws.

Velano Vascular’s blood-draw device resembles a common syringe.

It allows peripheral intravenous catheters to be repurposed to draw blood from patients, thereby reducing the need for additional needle sticks among patients receiving medications and hydration via intravenous delivery.

The single-use device will soon be used for clinical evaluation in select hospitals, including the University of Pennsylvania in Philadelphia and University Hospitals Case Medical Center of Cleveland in Ohio.

“A fundamental benefit of this technology is reducing the ‘pin cushion effect,’ in which hospitalized patients are ‘stuck’ several times daily to obtain blood tests,” said Eric M. Stone, co-founder and chief executive officer of Velano Vascular, the company developing the blood-draw device.

“Oftentimes, the draw procedure is plagued by multiple failed attempts. The FDA’s clearance of this novel technology validates the existing clinical need and will allow us to expedite our efforts to bring this innovation to patients, healthcare providers, and hospitals around the world.”

According to research conducted by Velano Vascular, 1 of every 3 hospital patients is stuck 2 or more times daily for blood draws, with a significant subset of these patients receiving 3 or more blood draws, along with numerous needle sticks.

Twenty-eight percent of adult venipunctures and 44% of pediatric venipunctures require more than one stick to successfully draw blood.

“Traditional blood draws are one of the most common and most problematic healthcare procedures,” said Karen Daley, PhD, RN, past president of the American Nurses Association and a healthcare worker safety advocate.

“It is an antiquated technology that creates pain and anxiety for many patients, a significant safety risk for healthcare professionals, and a real inefficiency in our healthcare system. Velano Vascular has developed a common-sense solution to this pervasive, long-standing problem.”

The blood-draw device

Photo courtesy of

Velano Vascular

The US Food and Drug Administration (FDA) has cleared for marketing a device that reduces the need for venipunctures for in-hospital blood draws.

Velano Vascular’s blood-draw device resembles a common syringe.

It allows peripheral intravenous catheters to be repurposed to draw blood from patients, thereby reducing the need for additional needle sticks among patients receiving medications and hydration via intravenous delivery.

The single-use device will soon be used for clinical evaluation in select hospitals, including the University of Pennsylvania in Philadelphia and University Hospitals Case Medical Center of Cleveland in Ohio.

“A fundamental benefit of this technology is reducing the ‘pin cushion effect,’ in which hospitalized patients are ‘stuck’ several times daily to obtain blood tests,” said Eric M. Stone, co-founder and chief executive officer of Velano Vascular, the company developing the blood-draw device.

“Oftentimes, the draw procedure is plagued by multiple failed attempts. The FDA’s clearance of this novel technology validates the existing clinical need and will allow us to expedite our efforts to bring this innovation to patients, healthcare providers, and hospitals around the world.”

According to research conducted by Velano Vascular, 1 of every 3 hospital patients is stuck 2 or more times daily for blood draws, with a significant subset of these patients receiving 3 or more blood draws, along with numerous needle sticks.

Twenty-eight percent of adult venipunctures and 44% of pediatric venipunctures require more than one stick to successfully draw blood.

“Traditional blood draws are one of the most common and most problematic healthcare procedures,” said Karen Daley, PhD, RN, past president of the American Nurses Association and a healthcare worker safety advocate.

“It is an antiquated technology that creates pain and anxiety for many patients, a significant safety risk for healthcare professionals, and a real inefficiency in our healthcare system. Velano Vascular has developed a common-sense solution to this pervasive, long-standing problem.”

The blood-draw device

Photo courtesy of

Velano Vascular

The US Food and Drug Administration (FDA) has cleared for marketing a device that reduces the need for venipunctures for in-hospital blood draws.

Velano Vascular’s blood-draw device resembles a common syringe.

It allows peripheral intravenous catheters to be repurposed to draw blood from patients, thereby reducing the need for additional needle sticks among patients receiving medications and hydration via intravenous delivery.

The single-use device will soon be used for clinical evaluation in select hospitals, including the University of Pennsylvania in Philadelphia and University Hospitals Case Medical Center of Cleveland in Ohio.

“A fundamental benefit of this technology is reducing the ‘pin cushion effect,’ in which hospitalized patients are ‘stuck’ several times daily to obtain blood tests,” said Eric M. Stone, co-founder and chief executive officer of Velano Vascular, the company developing the blood-draw device.

“Oftentimes, the draw procedure is plagued by multiple failed attempts. The FDA’s clearance of this novel technology validates the existing clinical need and will allow us to expedite our efforts to bring this innovation to patients, healthcare providers, and hospitals around the world.”

According to research conducted by Velano Vascular, 1 of every 3 hospital patients is stuck 2 or more times daily for blood draws, with a significant subset of these patients receiving 3 or more blood draws, along with numerous needle sticks.

Twenty-eight percent of adult venipunctures and 44% of pediatric venipunctures require more than one stick to successfully draw blood.

“Traditional blood draws are one of the most common and most problematic healthcare procedures,” said Karen Daley, PhD, RN, past president of the American Nurses Association and a healthcare worker safety advocate.

“It is an antiquated technology that creates pain and anxiety for many patients, a significant safety risk for healthcare professionals, and a real inefficiency in our healthcare system. Velano Vascular has developed a common-sense solution to this pervasive, long-standing problem.”