Evidence is becoming overwhelming that ambulatory blood pressure monitoring is the only reliable way to measure blood pressure for both diagnosing hypertension and following patients once they are diagnosed.

Office-based blood pressure measurement is out, be it a one-off reading or a cluster of sequential readings during a single office visit. Ambulatory blood pressure monitoring (ABPM) increasingly is the standard of care.

Mitchel L. Zoler/Frontline Medical News

One recent nail in the coffin of office-based measurement came in a modestly-sized but revealing study reported by Dr. Joyce P. Samuel, a pediatric hypertension specialist at the University of Texas in Houston. She reported her experience directly comparing ambulatory and carefully-done office-based blood pressure measurement in a presentation at the annual meeting of the Pediatric Academic Societies in Baltimore.

Dr. Samuel followed 40 patients age 9-21 years whom she had previously diagnosed with essential hypertension (children with a systolic blood pressure at or above the 95th percentile for sex, age, and height), and repeatedly measured their blood pressures by both ambulatory and office-based readings at 2-week intervals as she searched for the best combination of antihypertensive drugs for each patient. She sent patients home for 24 hours of blood-pressure monitoring with an ambulatory device, and when they returned to her office the next day, she performed an office-based measurement using meticulous technique: Each child was seated and calm, measured on the right arm, with four measurements taken sequentially at about 1 minute intervals with the first reading discarded and the remaining three averaged.

Over the course of several months, she collected 173 paired ambulatory and office-based systolic blood pressure readings from individual patients. Substantial differences between the two forms of measurement were remarkably common. In 20% of the pairs, the ambulatory systolic reading was at least 10 mm Hg higher than the office-based reading, and for some pairs the differences ran as high as 30 mm Hg. In an additional 32% of the paired readings, office-based systolic pressure ran at least 10 mm Hg higher and in some cases as much as 35 mm Hg higher than the ambulatory reading.

Dr. Samuel also analyzed her findings a different way to assess the clinical consequences of these differences based on whether a child’s systolic pressure identified the patient as normotensive, hypertensive, or prehypertensive (a systolic pressure at the 90-94th percentile for the child’s age, sex and height). She found that the diagnoses matched for only 49% of the paired measurements. In 24% of the paired readings, ABPM identified children with hypertension that was not seen with concurrent office-based measurement, cases of masked hypertension. In 17% of the pairs, office-based measurement diagnosed hypertension that was not confirmed by ABPM, cases of white-coat hypertension. The remaining 10% of pairs were mismatched by showing normotensive with one method and prehypertensive with the other method. Dr. Samuel searched for any consistent patterns in these differences and found none. The disparate results with ambulatory and office-based measurements seemed almost random, with no correlation with age, sex, race, the medications patients received, or how many times a patient had already undergone dual blood-pressure monitoring. Individual patients had no meaningful differences between some of their paired measurements but had a meaningful disparity for others.

“We were unable to predict discrepancies,” said Dr. Samuels.

“You can’t get around it, you need ambulatory blood pressure monitoring to make the best diagnosis” of hypertension, she told me. “We need to push to make ambulatory monitoring more available. I am moving toward believing that ambulatory blood pressure monitoring must be routinely done on everyone. This is what the data suggest.”

It’s also where medicine is headed. In 2015, the U.S. Preventative Services Task Force (USPSTF) issued new recommendations for hypertension screening in adults aged 18 years or older, indicating that there was “convincing evidence that ABPM is the best method for diagnosing hypertension,” and the agency further recommended that ABPM is “the reference standard for confirming the diagnosis of hypertension.” Another endorsement of ambulatory blood pressure monitoring came out last year from the International Society for Chronobiology.

Recommendations are not yet as evolved for children. The USPSTF last weighed in on screening kids for hypertension in 2013, and said the evidence as of then was “insufficient” to assess the benefits and harms of screening for hypertension in children and adolescents. That document endorsed careful office-based blood pressure measurement, which highlights how recently expert sentiment has shifted on the issue of measurement. In response to the USPSTF 2013 statement, the American Academy of Pediatrics noted that it continued to back recommendations that are more than a decade old from the National High Blood Pressure Education Program that called for hypertension screening in children starting when they are 3 years old. Neither of these two groups has made any recent statement about the preferred method to measure blood pressure.

[email protected]

On Twitter @mitchelzoler

Evidence is becoming overwhelming that ambulatory blood pressure monitoring is the only reliable way to measure blood pressure for both diagnosing hypertension and following patients once they are diagnosed.

Office-based blood pressure measurement is out, be it a one-off reading or a cluster of sequential readings during a single office visit. Ambulatory blood pressure monitoring (ABPM) increasingly is the standard of care.

Mitchel L. Zoler/Frontline Medical News

One recent nail in the coffin of office-based measurement came in a modestly-sized but revealing study reported by Dr. Joyce P. Samuel, a pediatric hypertension specialist at the University of Texas in Houston. She reported her experience directly comparing ambulatory and carefully-done office-based blood pressure measurement in a presentation at the annual meeting of the Pediatric Academic Societies in Baltimore.

Dr. Samuel followed 40 patients age 9-21 years whom she had previously diagnosed with essential hypertension (children with a systolic blood pressure at or above the 95th percentile for sex, age, and height), and repeatedly measured their blood pressures by both ambulatory and office-based readings at 2-week intervals as she searched for the best combination of antihypertensive drugs for each patient. She sent patients home for 24 hours of blood-pressure monitoring with an ambulatory device, and when they returned to her office the next day, she performed an office-based measurement using meticulous technique: Each child was seated and calm, measured on the right arm, with four measurements taken sequentially at about 1 minute intervals with the first reading discarded and the remaining three averaged.

Over the course of several months, she collected 173 paired ambulatory and office-based systolic blood pressure readings from individual patients. Substantial differences between the two forms of measurement were remarkably common. In 20% of the pairs, the ambulatory systolic reading was at least 10 mm Hg higher than the office-based reading, and for some pairs the differences ran as high as 30 mm Hg. In an additional 32% of the paired readings, office-based systolic pressure ran at least 10 mm Hg higher and in some cases as much as 35 mm Hg higher than the ambulatory reading.

Dr. Samuel also analyzed her findings a different way to assess the clinical consequences of these differences based on whether a child’s systolic pressure identified the patient as normotensive, hypertensive, or prehypertensive (a systolic pressure at the 90-94th percentile for the child’s age, sex and height). She found that the diagnoses matched for only 49% of the paired measurements. In 24% of the paired readings, ABPM identified children with hypertension that was not seen with concurrent office-based measurement, cases of masked hypertension. In 17% of the pairs, office-based measurement diagnosed hypertension that was not confirmed by ABPM, cases of white-coat hypertension. The remaining 10% of pairs were mismatched by showing normotensive with one method and prehypertensive with the other method. Dr. Samuel searched for any consistent patterns in these differences and found none. The disparate results with ambulatory and office-based measurements seemed almost random, with no correlation with age, sex, race, the medications patients received, or how many times a patient had already undergone dual blood-pressure monitoring. Individual patients had no meaningful differences between some of their paired measurements but had a meaningful disparity for others.

“We were unable to predict discrepancies,” said Dr. Samuels.

“You can’t get around it, you need ambulatory blood pressure monitoring to make the best diagnosis” of hypertension, she told me. “We need to push to make ambulatory monitoring more available. I am moving toward believing that ambulatory blood pressure monitoring must be routinely done on everyone. This is what the data suggest.”

It’s also where medicine is headed. In 2015, the U.S. Preventative Services Task Force (USPSTF) issued new recommendations for hypertension screening in adults aged 18 years or older, indicating that there was “convincing evidence that ABPM is the best method for diagnosing hypertension,” and the agency further recommended that ABPM is “the reference standard for confirming the diagnosis of hypertension.” Another endorsement of ambulatory blood pressure monitoring came out last year from the International Society for Chronobiology.

Recommendations are not yet as evolved for children. The USPSTF last weighed in on screening kids for hypertension in 2013, and said the evidence as of then was “insufficient” to assess the benefits and harms of screening for hypertension in children and adolescents. That document endorsed careful office-based blood pressure measurement, which highlights how recently expert sentiment has shifted on the issue of measurement. In response to the USPSTF 2013 statement, the American Academy of Pediatrics noted that it continued to back recommendations that are more than a decade old from the National High Blood Pressure Education Program that called for hypertension screening in children starting when they are 3 years old. Neither of these two groups has made any recent statement about the preferred method to measure blood pressure.

[email protected]

On Twitter @mitchelzoler

Evidence is becoming overwhelming that ambulatory blood pressure monitoring is the only reliable way to measure blood pressure for both diagnosing hypertension and following patients once they are diagnosed.

Office-based blood pressure measurement is out, be it a one-off reading or a cluster of sequential readings during a single office visit. Ambulatory blood pressure monitoring (ABPM) increasingly is the standard of care.

Mitchel L. Zoler/Frontline Medical News

One recent nail in the coffin of office-based measurement came in a modestly-sized but revealing study reported by Dr. Joyce P. Samuel, a pediatric hypertension specialist at the University of Texas in Houston. She reported her experience directly comparing ambulatory and carefully-done office-based blood pressure measurement in a presentation at the annual meeting of the Pediatric Academic Societies in Baltimore.

Dr. Samuel followed 40 patients age 9-21 years whom she had previously diagnosed with essential hypertension (children with a systolic blood pressure at or above the 95th percentile for sex, age, and height), and repeatedly measured their blood pressures by both ambulatory and office-based readings at 2-week intervals as she searched for the best combination of antihypertensive drugs for each patient. She sent patients home for 24 hours of blood-pressure monitoring with an ambulatory device, and when they returned to her office the next day, she performed an office-based measurement using meticulous technique: Each child was seated and calm, measured on the right arm, with four measurements taken sequentially at about 1 minute intervals with the first reading discarded and the remaining three averaged.

Over the course of several months, she collected 173 paired ambulatory and office-based systolic blood pressure readings from individual patients. Substantial differences between the two forms of measurement were remarkably common. In 20% of the pairs, the ambulatory systolic reading was at least 10 mm Hg higher than the office-based reading, and for some pairs the differences ran as high as 30 mm Hg. In an additional 32% of the paired readings, office-based systolic pressure ran at least 10 mm Hg higher and in some cases as much as 35 mm Hg higher than the ambulatory reading.

Dr. Samuel also analyzed her findings a different way to assess the clinical consequences of these differences based on whether a child’s systolic pressure identified the patient as normotensive, hypertensive, or prehypertensive (a systolic pressure at the 90-94th percentile for the child’s age, sex and height). She found that the diagnoses matched for only 49% of the paired measurements. In 24% of the paired readings, ABPM identified children with hypertension that was not seen with concurrent office-based measurement, cases of masked hypertension. In 17% of the pairs, office-based measurement diagnosed hypertension that was not confirmed by ABPM, cases of white-coat hypertension. The remaining 10% of pairs were mismatched by showing normotensive with one method and prehypertensive with the other method. Dr. Samuel searched for any consistent patterns in these differences and found none. The disparate results with ambulatory and office-based measurements seemed almost random, with no correlation with age, sex, race, the medications patients received, or how many times a patient had already undergone dual blood-pressure monitoring. Individual patients had no meaningful differences between some of their paired measurements but had a meaningful disparity for others.

“We were unable to predict discrepancies,” said Dr. Samuels.

“You can’t get around it, you need ambulatory blood pressure monitoring to make the best diagnosis” of hypertension, she told me. “We need to push to make ambulatory monitoring more available. I am moving toward believing that ambulatory blood pressure monitoring must be routinely done on everyone. This is what the data suggest.”

It’s also where medicine is headed. In 2015, the U.S. Preventative Services Task Force (USPSTF) issued new recommendations for hypertension screening in adults aged 18 years or older, indicating that there was “convincing evidence that ABPM is the best method for diagnosing hypertension,” and the agency further recommended that ABPM is “the reference standard for confirming the diagnosis of hypertension.” Another endorsement of ambulatory blood pressure monitoring came out last year from the International Society for Chronobiology.

Recommendations are not yet as evolved for children. The USPSTF last weighed in on screening kids for hypertension in 2013, and said the evidence as of then was “insufficient” to assess the benefits and harms of screening for hypertension in children and adolescents. That document endorsed careful office-based blood pressure measurement, which highlights how recently expert sentiment has shifted on the issue of measurement. In response to the USPSTF 2013 statement, the American Academy of Pediatrics noted that it continued to back recommendations that are more than a decade old from the National High Blood Pressure Education Program that called for hypertension screening in children starting when they are 3 years old. Neither of these two groups has made any recent statement about the preferred method to measure blood pressure.

[email protected]

On Twitter @mitchelzoler

Exposure to Candida albicans significantly increased the odds of a schizophrenia diagnosis in men, according to case-control data from two cohorts of 947 adults.

“Fungal pathogens have not been extensively evaluated in studies of psychiatric disorders,” wrote Dr. Emily G. Severance of Johns Hopkins University in Baltimore, and her colleagues, in njp (Nature Partner Journals) Schizophrenia.

GrahamColm/Wikimedia Commons

The researchers compared C. albicans IgG levels of individuals with schizophrenia and bipolar disorder with controls and found no diagnostic differences. However, stratification by sex showed a significantly increased risk of schizophrenia in men with elevated C. albicans IgG levels, with a ninefold increase in risk at the highest of three levels of seropositivity (odds ratio, 9.53). Elevated C. albicans levels in males with bipolar disorder were attributed to a history of homelessness.

C. albicans antibodies in women were not significantly different between groups. However, C. albicans was significantly associated with cognitive impairment in women with schizophrenia vs. control women (OR, 1.12), but no such difference was noted in men.

High levels of C. albicans antibodies were associated with comorbid gastrointestinal, genitourinary, and neoplastic conditions among individuals with psychiatric disorders overall.

“It may be premature to list this pathogen as a risk factor for disease causation, but its status as a comorbidity requires clinical attention,” the researchers wrote. “In the long term, more research is required to understand the mechanisms that trigger pathogenicity of fungal commensals and how this might impact brain function in psychiatric disorders.”

The findings were published in npj Schizophrenia. Read the full study here (npj Schizophrenia 2016 May 4. doi: 10.1038/npjschz.2016.18).

Exposure to Candida albicans significantly increased the odds of a schizophrenia diagnosis in men, according to case-control data from two cohorts of 947 adults.

“Fungal pathogens have not been extensively evaluated in studies of psychiatric disorders,” wrote Dr. Emily G. Severance of Johns Hopkins University in Baltimore, and her colleagues, in njp (Nature Partner Journals) Schizophrenia.

GrahamColm/Wikimedia Commons

The researchers compared C. albicans IgG levels of individuals with schizophrenia and bipolar disorder with controls and found no diagnostic differences. However, stratification by sex showed a significantly increased risk of schizophrenia in men with elevated C. albicans IgG levels, with a ninefold increase in risk at the highest of three levels of seropositivity (odds ratio, 9.53). Elevated C. albicans levels in males with bipolar disorder were attributed to a history of homelessness.

C. albicans antibodies in women were not significantly different between groups. However, C. albicans was significantly associated with cognitive impairment in women with schizophrenia vs. control women (OR, 1.12), but no such difference was noted in men.

High levels of C. albicans antibodies were associated with comorbid gastrointestinal, genitourinary, and neoplastic conditions among individuals with psychiatric disorders overall.

“It may be premature to list this pathogen as a risk factor for disease causation, but its status as a comorbidity requires clinical attention,” the researchers wrote. “In the long term, more research is required to understand the mechanisms that trigger pathogenicity of fungal commensals and how this might impact brain function in psychiatric disorders.”

The findings were published in npj Schizophrenia. Read the full study here (npj Schizophrenia 2016 May 4. doi: 10.1038/npjschz.2016.18).

Exposure to Candida albicans significantly increased the odds of a schizophrenia diagnosis in men, according to case-control data from two cohorts of 947 adults.

“Fungal pathogens have not been extensively evaluated in studies of psychiatric disorders,” wrote Dr. Emily G. Severance of Johns Hopkins University in Baltimore, and her colleagues, in njp (Nature Partner Journals) Schizophrenia.

GrahamColm/Wikimedia Commons

The researchers compared C. albicans IgG levels of individuals with schizophrenia and bipolar disorder with controls and found no diagnostic differences. However, stratification by sex showed a significantly increased risk of schizophrenia in men with elevated C. albicans IgG levels, with a ninefold increase in risk at the highest of three levels of seropositivity (odds ratio, 9.53). Elevated C. albicans levels in males with bipolar disorder were attributed to a history of homelessness.

C. albicans antibodies in women were not significantly different between groups. However, C. albicans was significantly associated with cognitive impairment in women with schizophrenia vs. control women (OR, 1.12), but no such difference was noted in men.

High levels of C. albicans antibodies were associated with comorbid gastrointestinal, genitourinary, and neoplastic conditions among individuals with psychiatric disorders overall.

“It may be premature to list this pathogen as a risk factor for disease causation, but its status as a comorbidity requires clinical attention,” the researchers wrote. “In the long term, more research is required to understand the mechanisms that trigger pathogenicity of fungal commensals and how this might impact brain function in psychiatric disorders.”

The findings were published in npj Schizophrenia. Read the full study here (npj Schizophrenia 2016 May 4. doi: 10.1038/npjschz.2016.18).

I am pleased to welcome you to the first Vascular Quality Initiative (VQI) Annual Meeting (VQI@VAM), which will be held on June 8th, in conjunction with this year’s Vascular Annual Meeting at Gaylord National Resort & Convention Center. We have scheduled a full day program of practical QI sessions, including presentations from both QI leaders and VQI members who will be sharing their experiences in sessions designed to benefit both vascular specialists and quality improvement professionals.

We are very fortunate to have two QI experts joining us – Dr. Michael Englesbe from the Michigan Surgical Quality Collaborative and Dr. Ted James from the University of Vermont – who will provide their perspectives on how we can drive quality with the VQI registries. Dr. Englesbe, as our keynote speaker, and Dr. James, our quality expert, will be addressing the practicalities, opportunities, and challenges of using registry data for quality improvement. Dr. James will also be moderating case study discussion with centers from across the country to help VQI members use the QI tools and VQI data effectively in their own practices. All the sessions are geared to demonstrating practical QI skills so that attendees can leverage their own VQI data and reporting, and discuss solutions. Registration and a $100 fee are required.

Overall, I believe that the Annual Meeting will create a valuable opportunity for both vascular specialists and quality improvement staff to see how participation in VQI can help improve the day-to-day quality of vascular care for patients. By taking a team approach, those who attend will be able to share a combination of best practice, collaboration, and benchmarking. Data managers will gain deeper insights into the value of reporting and analytics, and practitioners will able to compare their experiences with others.

This inaugural VQI Annual Meeting is an important part of our road map to the next level for the Vascular Quality Initiative’s development. It allows us to directly reach our base of over 2,800 physicians to introduce new approaches, such as tracking long-term follow-up and better measurement of the quality of vascular care, which will increase our effectiveness as practitioners.

Over the years of development of the VQI, we’ve seen the value of quality improvement data and analytics for the VQI in our practices. Now we’ve developed a valuable body of VQI-based real world experience to draw upon, which we will demonstrate at this event and going forward. I look forward to seeing you at the Gaylord National Resort & Convention Center on June 8th for VQI@VAM.

Dr. Larry Kraiss
Chair, SVS PSO Governing Council

I am pleased to welcome you to the first Vascular Quality Initiative (VQI) Annual Meeting (VQI@VAM), which will be held on June 8th, in conjunction with this year’s Vascular Annual Meeting at Gaylord National Resort & Convention Center. We have scheduled a full day program of practical QI sessions, including presentations from both QI leaders and VQI members who will be sharing their experiences in sessions designed to benefit both vascular specialists and quality improvement professionals.

We are very fortunate to have two QI experts joining us – Dr. Michael Englesbe from the Michigan Surgical Quality Collaborative and Dr. Ted James from the University of Vermont – who will provide their perspectives on how we can drive quality with the VQI registries. Dr. Englesbe, as our keynote speaker, and Dr. James, our quality expert, will be addressing the practicalities, opportunities, and challenges of using registry data for quality improvement. Dr. James will also be moderating case study discussion with centers from across the country to help VQI members use the QI tools and VQI data effectively in their own practices. All the sessions are geared to demonstrating practical QI skills so that attendees can leverage their own VQI data and reporting, and discuss solutions. Registration and a $100 fee are required.

Overall, I believe that the Annual Meeting will create a valuable opportunity for both vascular specialists and quality improvement staff to see how participation in VQI can help improve the day-to-day quality of vascular care for patients. By taking a team approach, those who attend will be able to share a combination of best practice, collaboration, and benchmarking. Data managers will gain deeper insights into the value of reporting and analytics, and practitioners will able to compare their experiences with others.

This inaugural VQI Annual Meeting is an important part of our road map to the next level for the Vascular Quality Initiative’s development. It allows us to directly reach our base of over 2,800 physicians to introduce new approaches, such as tracking long-term follow-up and better measurement of the quality of vascular care, which will increase our effectiveness as practitioners.

Over the years of development of the VQI, we’ve seen the value of quality improvement data and analytics for the VQI in our practices. Now we’ve developed a valuable body of VQI-based real world experience to draw upon, which we will demonstrate at this event and going forward. I look forward to seeing you at the Gaylord National Resort & Convention Center on June 8th for VQI@VAM.

Dr. Larry Kraiss
Chair, SVS PSO Governing Council

I am pleased to welcome you to the first Vascular Quality Initiative (VQI) Annual Meeting (VQI@VAM), which will be held on June 8th, in conjunction with this year’s Vascular Annual Meeting at Gaylord National Resort & Convention Center. We have scheduled a full day program of practical QI sessions, including presentations from both QI leaders and VQI members who will be sharing their experiences in sessions designed to benefit both vascular specialists and quality improvement professionals.

We are very fortunate to have two QI experts joining us – Dr. Michael Englesbe from the Michigan Surgical Quality Collaborative and Dr. Ted James from the University of Vermont – who will provide their perspectives on how we can drive quality with the VQI registries. Dr. Englesbe, as our keynote speaker, and Dr. James, our quality expert, will be addressing the practicalities, opportunities, and challenges of using registry data for quality improvement. Dr. James will also be moderating case study discussion with centers from across the country to help VQI members use the QI tools and VQI data effectively in their own practices. All the sessions are geared to demonstrating practical QI skills so that attendees can leverage their own VQI data and reporting, and discuss solutions. Registration and a $100 fee are required.

Overall, I believe that the Annual Meeting will create a valuable opportunity for both vascular specialists and quality improvement staff to see how participation in VQI can help improve the day-to-day quality of vascular care for patients. By taking a team approach, those who attend will be able to share a combination of best practice, collaboration, and benchmarking. Data managers will gain deeper insights into the value of reporting and analytics, and practitioners will able to compare their experiences with others.

This inaugural VQI Annual Meeting is an important part of our road map to the next level for the Vascular Quality Initiative’s development. It allows us to directly reach our base of over 2,800 physicians to introduce new approaches, such as tracking long-term follow-up and better measurement of the quality of vascular care, which will increase our effectiveness as practitioners.

Over the years of development of the VQI, we’ve seen the value of quality improvement data and analytics for the VQI in our practices. Now we’ve developed a valuable body of VQI-based real world experience to draw upon, which we will demonstrate at this event and going forward. I look forward to seeing you at the Gaylord National Resort & Convention Center on June 8th for VQI@VAM.

Dr. Larry Kraiss
Chair, SVS PSO Governing Council

In past years the Crawford Critical Issues Symposium has served as a forum in which nonclinical issues took center stage. At the 2016 Vascular Annual Meeting, Dr. Ron Fairman of the University of Pennsylvania Health System will take the symposium in a clinical direction with an issue that, he says, highlights critical questions about appropriateness of care. Titled “In Search of Clarity,” speakers will talk about interventions for claudication in the superficial femoral-popliteal arteries. This year’s lineup will address the role of medical management and exercise, along with the choice, cost, and durability of common interventions.

Speakers will be:

Courtesy University of Pennsylvania

Dr. Mary McDermott of Northwestern University, on exercise;

Dr. Elizabeth Ratchford, Johns Hopkins University on medical management;

Dr. Michael Conte, of the University of California San Francisco, on understanding data sets, durability, and guidelines;

Dr. Peter Schneider of Kaiser Permanente on how claudication is approached in a system outside the traditional fee-for-service model;

Dr. Dennis Gable of Texas Vascular Associates on approaches to claudication in the community practice setting; and

Dr. Robert Zwolak of Dartmouth-Hitchcock Medical Center on the financial aspects, including hidden costs.

VC: Why did you choose claudication as this year’s key theme?

Dr. Fairman: There is probably no other subject that touches more on appropriateness of care than interventions for claudication, and if you look at how patients are managed across the country, there probably is no greater area of disparity. One of the most significant aspects of treating patients with expensive interventions for claudication is frequently the lack of durability. We often see patients in the office who present for a second opinion who already have undergone multiple invasive interventions over a 1- to 2-year period, all resulting in short-term improvement followed by – frighteningly – a much more serious set of symptoms than they started with. And this is fostered by a reimbursement system that demonstrates a willingness to reimburse physicians and hospitals for procedures that have little durability.

VC: Is there too much of a leap in the vascular community to invasive interventions?

Dr. Fairman: I believe that the members of our society understand that before a patient is considered for an invasive intervention for claudication, they should undergo exercise training and optimization of their medical status – but there are challenges associated with that. How do you do get a patient connected to a training regimen? Have all the patient’s risk factors been effectively addressed? Have they quit smoking? Is their blood sugar under control? We view ourselves as a unique specialty that offers comprehensive care of patients with vascular disease. We don’t just do surgery and procedures, but we have the ability to offer the entire package. We also understand by virtue of our training the natural history of the anatomic lesions we are treating. It is essential that physicians look at the whole patient before planning an intervention, and this forum should help us think more about that.

VC: What’s missing from a research perspective that might shed light on when intervention is needed and which interventions to perform?

Dr. Fairman: We need studies comparing durability of interventions with longer follow-up; 1 year is not enough. Dr. Conte will address what the available large data sets show in terms of durability. We need real-world data that compare technologies for claudication. We all have biases about technology based on our own experiences, but many of us struggle in selecting from the very many interventional options available to treat our patients. In addition, physician reimbursement typically increases from simple balloon angioplasty, to placement of a stent, to atherectomy.

VC: What other cost and reimbursement issues do you expect to deal with during the symposium?

I’m interested in Dr. Schneider’s perspective practicing in a health system that is a non–fee-for-service model. How does he make day-to-day decisions about using technology? Dr. Zwolek will talk about the financial side, not only in terms of physician reimbursement, but how physicians should view the expensive disposable inventory that they use when treating patients with claudication. This relates to hospital or facility reimbursement and issues related to margin. Regrettably, given the time constraints of this program, we were unable to secure speakers representing the viewpoints and perspectives of CMS [the Centers for Medicare and Medicaid Services] and the FDA [Food and Drug Administration].

In past years the Crawford Critical Issues Symposium has served as a forum in which nonclinical issues took center stage. At the 2016 Vascular Annual Meeting, Dr. Ron Fairman of the University of Pennsylvania Health System will take the symposium in a clinical direction with an issue that, he says, highlights critical questions about appropriateness of care. Titled “In Search of Clarity,” speakers will talk about interventions for claudication in the superficial femoral-popliteal arteries. This year’s lineup will address the role of medical management and exercise, along with the choice, cost, and durability of common interventions.

Speakers will be:

Courtesy University of Pennsylvania

Dr. Mary McDermott of Northwestern University, on exercise;

Dr. Elizabeth Ratchford, Johns Hopkins University on medical management;

Dr. Michael Conte, of the University of California San Francisco, on understanding data sets, durability, and guidelines;

Dr. Peter Schneider of Kaiser Permanente on how claudication is approached in a system outside the traditional fee-for-service model;

Dr. Dennis Gable of Texas Vascular Associates on approaches to claudication in the community practice setting; and

Dr. Robert Zwolak of Dartmouth-Hitchcock Medical Center on the financial aspects, including hidden costs.

VC: Why did you choose claudication as this year’s key theme?

Dr. Fairman: There is probably no other subject that touches more on appropriateness of care than interventions for claudication, and if you look at how patients are managed across the country, there probably is no greater area of disparity. One of the most significant aspects of treating patients with expensive interventions for claudication is frequently the lack of durability. We often see patients in the office who present for a second opinion who already have undergone multiple invasive interventions over a 1- to 2-year period, all resulting in short-term improvement followed by – frighteningly – a much more serious set of symptoms than they started with. And this is fostered by a reimbursement system that demonstrates a willingness to reimburse physicians and hospitals for procedures that have little durability.

VC: Is there too much of a leap in the vascular community to invasive interventions?

Dr. Fairman: I believe that the members of our society understand that before a patient is considered for an invasive intervention for claudication, they should undergo exercise training and optimization of their medical status – but there are challenges associated with that. How do you do get a patient connected to a training regimen? Have all the patient’s risk factors been effectively addressed? Have they quit smoking? Is their blood sugar under control? We view ourselves as a unique specialty that offers comprehensive care of patients with vascular disease. We don’t just do surgery and procedures, but we have the ability to offer the entire package. We also understand by virtue of our training the natural history of the anatomic lesions we are treating. It is essential that physicians look at the whole patient before planning an intervention, and this forum should help us think more about that.

VC: What’s missing from a research perspective that might shed light on when intervention is needed and which interventions to perform?

Dr. Fairman: We need studies comparing durability of interventions with longer follow-up; 1 year is not enough. Dr. Conte will address what the available large data sets show in terms of durability. We need real-world data that compare technologies for claudication. We all have biases about technology based on our own experiences, but many of us struggle in selecting from the very many interventional options available to treat our patients. In addition, physician reimbursement typically increases from simple balloon angioplasty, to placement of a stent, to atherectomy.

VC: What other cost and reimbursement issues do you expect to deal with during the symposium?

I’m interested in Dr. Schneider’s perspective practicing in a health system that is a non–fee-for-service model. How does he make day-to-day decisions about using technology? Dr. Zwolek will talk about the financial side, not only in terms of physician reimbursement, but how physicians should view the expensive disposable inventory that they use when treating patients with claudication. This relates to hospital or facility reimbursement and issues related to margin. Regrettably, given the time constraints of this program, we were unable to secure speakers representing the viewpoints and perspectives of CMS [the Centers for Medicare and Medicaid Services] and the FDA [Food and Drug Administration].

In past years the Crawford Critical Issues Symposium has served as a forum in which nonclinical issues took center stage. At the 2016 Vascular Annual Meeting, Dr. Ron Fairman of the University of Pennsylvania Health System will take the symposium in a clinical direction with an issue that, he says, highlights critical questions about appropriateness of care. Titled “In Search of Clarity,” speakers will talk about interventions for claudication in the superficial femoral-popliteal arteries. This year’s lineup will address the role of medical management and exercise, along with the choice, cost, and durability of common interventions.

Speakers will be:

Courtesy University of Pennsylvania

Dr. Mary McDermott of Northwestern University, on exercise;

Dr. Elizabeth Ratchford, Johns Hopkins University on medical management;

Dr. Michael Conte, of the University of California San Francisco, on understanding data sets, durability, and guidelines;

Dr. Peter Schneider of Kaiser Permanente on how claudication is approached in a system outside the traditional fee-for-service model;

Dr. Dennis Gable of Texas Vascular Associates on approaches to claudication in the community practice setting; and

Dr. Robert Zwolak of Dartmouth-Hitchcock Medical Center on the financial aspects, including hidden costs.

VC: Why did you choose claudication as this year’s key theme?

Dr. Fairman: There is probably no other subject that touches more on appropriateness of care than interventions for claudication, and if you look at how patients are managed across the country, there probably is no greater area of disparity. One of the most significant aspects of treating patients with expensive interventions for claudication is frequently the lack of durability. We often see patients in the office who present for a second opinion who already have undergone multiple invasive interventions over a 1- to 2-year period, all resulting in short-term improvement followed by – frighteningly – a much more serious set of symptoms than they started with. And this is fostered by a reimbursement system that demonstrates a willingness to reimburse physicians and hospitals for procedures that have little durability.

VC: Is there too much of a leap in the vascular community to invasive interventions?

Dr. Fairman: I believe that the members of our society understand that before a patient is considered for an invasive intervention for claudication, they should undergo exercise training and optimization of their medical status – but there are challenges associated with that. How do you do get a patient connected to a training regimen? Have all the patient’s risk factors been effectively addressed? Have they quit smoking? Is their blood sugar under control? We view ourselves as a unique specialty that offers comprehensive care of patients with vascular disease. We don’t just do surgery and procedures, but we have the ability to offer the entire package. We also understand by virtue of our training the natural history of the anatomic lesions we are treating. It is essential that physicians look at the whole patient before planning an intervention, and this forum should help us think more about that.

VC: What’s missing from a research perspective that might shed light on when intervention is needed and which interventions to perform?

Dr. Fairman: We need studies comparing durability of interventions with longer follow-up; 1 year is not enough. Dr. Conte will address what the available large data sets show in terms of durability. We need real-world data that compare technologies for claudication. We all have biases about technology based on our own experiences, but many of us struggle in selecting from the very many interventional options available to treat our patients. In addition, physician reimbursement typically increases from simple balloon angioplasty, to placement of a stent, to atherectomy.

VC: What other cost and reimbursement issues do you expect to deal with during the symposium?

I’m interested in Dr. Schneider’s perspective practicing in a health system that is a non–fee-for-service model. How does he make day-to-day decisions about using technology? Dr. Zwolek will talk about the financial side, not only in terms of physician reimbursement, but how physicians should view the expensive disposable inventory that they use when treating patients with claudication. This relates to hospital or facility reimbursement and issues related to margin. Regrettably, given the time constraints of this program, we were unable to secure speakers representing the viewpoints and perspectives of CMS [the Centers for Medicare and Medicaid Services] and the FDA [Food and Drug Administration].

Our nation’s capital is the perfect venue for the pre-eminent vascular surgical educational and social meeting of the year – the 2016 SVS Vascular Annual Meeting on June 8-11.

This year’s meeting will be the most educationally jam-packed and stimulating annual meeting in our Society’s 70-year history, and a “must-attend” event for all serious health care professionals caring for patients with circulatory disease who want to succeed in our rapidly changing and challenging health care system and economy.

Recognizing that the majority of vascular surgical care in the United States is delivered in the community by nonacademic surgeons, our Program Committee, under the direction of my leadership team, has focused the Annual Meeting on the practical educational needs of our community practice SVS members. This includes the latest clinical research and results of evolving endovascular therapeutic interventions, “how-to” videos, focused hands-on training sessions, postgraduate courses geared to the contemporary practicing vascular surgeon and named lectureships delivered by visionary international leaders such as Dr. Frank Veith, the Homans Lecturer.

Here is just some of what you’ll experience this year: Hands-on training and sessions focused on topics such as the multidisciplinary management of the diabetic foot; the impact on vascular surgery practices of changing reimbursement models; contemporary management of intermittent claudication; and much, much more.

• More presentations and clinically focused sessions than ever before, with real-time audience interaction with the speakers and panelists to enhance the educational experience.

• CME and self-assessment credits to satisfy your MOC requirements in a user-friendly fashion in one meeting.

• An extensive offering of industry-sponsored educational presentations focused on “what is next,” to keep you ahead of the competition.

• Events for our growing roster of international guests, including International Forum, International Fast Talk, and the International Reception.

• The interactive “Vascular LIVE,” showcasing the latest technology.

• Social events to mingle and chat with your colleagues and international vascular leaders.

The Gaylord National Resort & Convention Center is a spectacular luxury property on the Potomac River in National Harbor, just outside Washington, D.C., and a ferry ride across the river from historic Old Town Alexandria, Va.

Registration is open and ahead of last year’s pace! Check the VAM housing link online for hotel availability and www.vsweb.org/VAM2016 for more information. I look forward to welcoming you to Washington, D.C., in June to celebrate our specialty and to learn together.

Bruce A. Perler, M.D.
SVS President

Our nation’s capital is the perfect venue for the pre-eminent vascular surgical educational and social meeting of the year – the 2016 SVS Vascular Annual Meeting on June 8-11.

This year’s meeting will be the most educationally jam-packed and stimulating annual meeting in our Society’s 70-year history, and a “must-attend” event for all serious health care professionals caring for patients with circulatory disease who want to succeed in our rapidly changing and challenging health care system and economy.

Recognizing that the majority of vascular surgical care in the United States is delivered in the community by nonacademic surgeons, our Program Committee, under the direction of my leadership team, has focused the Annual Meeting on the practical educational needs of our community practice SVS members. This includes the latest clinical research and results of evolving endovascular therapeutic interventions, “how-to” videos, focused hands-on training sessions, postgraduate courses geared to the contemporary practicing vascular surgeon and named lectureships delivered by visionary international leaders such as Dr. Frank Veith, the Homans Lecturer.

Here is just some of what you’ll experience this year: Hands-on training and sessions focused on topics such as the multidisciplinary management of the diabetic foot; the impact on vascular surgery practices of changing reimbursement models; contemporary management of intermittent claudication; and much, much more.

• More presentations and clinically focused sessions than ever before, with real-time audience interaction with the speakers and panelists to enhance the educational experience.

• CME and self-assessment credits to satisfy your MOC requirements in a user-friendly fashion in one meeting.

• An extensive offering of industry-sponsored educational presentations focused on “what is next,” to keep you ahead of the competition.

• Events for our growing roster of international guests, including International Forum, International Fast Talk, and the International Reception.

• The interactive “Vascular LIVE,” showcasing the latest technology.

• Social events to mingle and chat with your colleagues and international vascular leaders.

The Gaylord National Resort & Convention Center is a spectacular luxury property on the Potomac River in National Harbor, just outside Washington, D.C., and a ferry ride across the river from historic Old Town Alexandria, Va.

Registration is open and ahead of last year’s pace! Check the VAM housing link online for hotel availability and www.vsweb.org/VAM2016 for more information. I look forward to welcoming you to Washington, D.C., in June to celebrate our specialty and to learn together.

Bruce A. Perler, M.D.
SVS President

Our nation’s capital is the perfect venue for the pre-eminent vascular surgical educational and social meeting of the year – the 2016 SVS Vascular Annual Meeting on June 8-11.

This year’s meeting will be the most educationally jam-packed and stimulating annual meeting in our Society’s 70-year history, and a “must-attend” event for all serious health care professionals caring for patients with circulatory disease who want to succeed in our rapidly changing and challenging health care system and economy.

Recognizing that the majority of vascular surgical care in the United States is delivered in the community by nonacademic surgeons, our Program Committee, under the direction of my leadership team, has focused the Annual Meeting on the practical educational needs of our community practice SVS members. This includes the latest clinical research and results of evolving endovascular therapeutic interventions, “how-to” videos, focused hands-on training sessions, postgraduate courses geared to the contemporary practicing vascular surgeon and named lectureships delivered by visionary international leaders such as Dr. Frank Veith, the Homans Lecturer.

Here is just some of what you’ll experience this year: Hands-on training and sessions focused on topics such as the multidisciplinary management of the diabetic foot; the impact on vascular surgery practices of changing reimbursement models; contemporary management of intermittent claudication; and much, much more.

• More presentations and clinically focused sessions than ever before, with real-time audience interaction with the speakers and panelists to enhance the educational experience.

• CME and self-assessment credits to satisfy your MOC requirements in a user-friendly fashion in one meeting.

• An extensive offering of industry-sponsored educational presentations focused on “what is next,” to keep you ahead of the competition.

• Events for our growing roster of international guests, including International Forum, International Fast Talk, and the International Reception.

• The interactive “Vascular LIVE,” showcasing the latest technology.

• Social events to mingle and chat with your colleagues and international vascular leaders.

The Gaylord National Resort & Convention Center is a spectacular luxury property on the Potomac River in National Harbor, just outside Washington, D.C., and a ferry ride across the river from historic Old Town Alexandria, Va.

Registration is open and ahead of last year’s pace! Check the VAM housing link online for hotel availability and www.vsweb.org/VAM2016 for more information. I look forward to welcoming you to Washington, D.C., in June to celebrate our specialty and to learn together.

Bruce A. Perler, M.D.
SVS President

Growing up, Denisse Rojas Marquez rarely visited the doctor. As undocumented immigrants from Mexico, her family viewed medical care as a luxury and sought it only in emergencies.

“I would always wait until it was very severe to see a doctor,” said Ms. Rojas Marquez, who came to the United States as a toddler. “That’s still a mentality I have to train myself out of. Growing up, going to the doctor meant very expensive bills and navigating through very complex systems.”

At 26, Ms. Rojas Marquez is determined to become a physician and help bridge the gap between undocumented immigrants and medical care. She is close to making that dream a reality because of a 2012 policy called the Deferred Action for Childhood Arrivals (DACA), which protects undocumented immigrants brought to the United States as children from deportation and offers access to work authorization. The policy enabled Ms. Rojas Marquez to become one of the first undocumented students to attend the Icahn School of Medicine at Mount Sinai in New York.

Photo provided by Denisse Rojas

But the fate of Ms. Rojas Marquez’s medical education is in flux as the U.S. Supreme Court considers protections for undocumented immigrants in the case of Texas v. United States. In dispute is the constitutionality of two of President Obama’s immigration policies: the Deferred Action for Parents of Americans and Lawful Permanent Residents (DAPA) and expanded DACA. The former protects undocumented immigrants who are parents of U.S. citizens from deportation, if they meet certain criteria. The second extends work authorization under the original DACA program from 2 years to 3 years and broadens age requirements.

Texas and 25 other states have sued over the programs, arguing the president does not have the authority to issue the new immigration policies, and that the programs violate the Constitution as well as the Administrative Procedure Act for notice-and-comment rule making. High court justices heard oral arguments April 18.

The ruling could impact the growing number of medical students with DACA status across the country, and jeopardize the funding invested in their training. Sixty-one medical schools now accept applications from DACA applicants, according to data from the Association of American Medical Colleges (AAMC). In 2015, 46 students with DACA status applied to U.S. medical schools and 20 were enrolled. In 2016, more than double (112) applied, although enrollment data will not be available until year’s end. Neither AAMC nor the National Resident Matching Program collect data on residents with DACA status.

A high court ruling in favor of the states could lead to DACA’s undoing, said Michael M. Hethmon, an attorney for the Immigration Reform Law Institute in Washington, D.C. The institute issued a brief to the Supreme Court in support of Texas.

If Texas prevails, “it’ll be a matter of weeks before a similar challenge will be levied against DACA and a number of other related programs,” Mr. Hethmon said in an interview. “There will be no more legal justification for those programs that exist.”

Saving talent or wasting money?

Loyola University in Chicago has accepted more students with DACA status than any other U.S. medical school. The reasons are simple, said Mark Kuczewski, Ph.D., chair of medical education at Loyola’s Stritch School of Medicine.

“We’re in the business of taking outstanding students,” Dr. Kuczewski said in an interview. “If the student is outstanding, we want them in our applicant pool. Second, being bilingual and bicultural is extremely important. We have patient populations out there that are diverse and underserved. We want to utilize this talent.”

In the fall of 2014, Stritch enrolled seven medical students with DACA status; in 2014, they doubled that enrollment. The students competed on the same playing field as other applicants and received no special treatment, Dr. Kuczewski said.

DACA students do pose funding challenges, he acknowledged. Although the students are protected from deportation and receive work authorization, they don’t qualify for federal student loans. Medical schools must find unique ways to help DACA students finance their education. A major Catholic health system provides student loan packages for several DACA students at Stritch, Dr. Kuczewski said. DACA students can also apply for financial assistance through an AAMC assistance program.

Abhinav Janghala

“Medical students use copious amounts of federal student loans,” he said. “Somehow the school has to make up that difference. We’ve found partners, but they don’t have infinite capacity, so we have to keep going back and finding new partners each year.”

The University of California, San Francisco, also has opened its doors to DACA students. Now in his third year, Jirayut New Latthivongskorn is UCSF’s first undocumented medical student. His education is financed by grants, private funding, and donations, said Mr. Latthivongskorn who came to the United States from Thailand when he was 9 years old. He is cofounder of Pre-Health Dreamers, a network of undocumented students who plan to pursue medical careers.

Before DACA granted his entry into UCSF, Mr. Latthivongskorn was accustomed to barriers because of his undocumented status, including having to turn down a nearly full-ride scholarship from the University of California, Davis, after high school.

“It was devastating,” Mr. Latthivongskorn said in an interview. “It was one of the very first times where I felt different and thought, ‘This is not going to work. You are undocumented.’”

Mr. Latthivongskorn and his family scraped together money for him to complete his undergraduate degree at the University of California, Berkeley. California has since passed the DREAM Act, a law that allows undocumented immigrants to receive private scholarships funded through public universities.

Not everyone believes undocumented immigrants should get the chance to become U.S. physicians. Dr. Jane M. Orient, executive director of the Association of American Physicians and Surgeons, argued that undocumented immigrants are not the answer to curbing the physician shortage.

“In a country that’s supposed to be ruled by law, it seems incomprehensible that people who are violating the law should be given privileges over people who are here legally,” she said in an interview. “We desperately do need more physicians, but we should not be blocking Americans from having this opportunity.”

Dr. Shirie Leng, a Boston anesthesiologist, said DACA is promising in theory, but falls short in practical application.

“There’s no particular reason why [undocumented students] wouldn’t make great doctors,” said Dr. Leng. “The problem is funding related. You can give kids all the opportunity you want, but if you can’t pay for it, that seems to me to be the biggest sticking point.”

Basing admission policies on programs that are vulnerable could end poorly for schools and students, Dr. Leng added.

If DACA is revoked, “it’s not just a waste of money for the school, but a waste of time for the kids,” she said.

Protections hinge on Supreme Court … and next president

During oral arguments earlier this month, justices appeared to disagree on whether DAPA and expanded DACA were properly executed.

Associate Justice Anthony M. Kennedy indicated that the normal order of government policy making had been “turned upside down,” by the creation of the programs. Associate Justice Sonia Sotomayor, meanwhile, noted that immigration policies with broader reaches have been similarly instituted in the past.

A ruling for the government would mean the president can use his executive power to enact policies that run contrary to immigration laws already in place, said Mr. Hethmon, the D.C. attorney. Current immigration laws trump informal agency discretion and do not allow for the government’s “arbitrary and capricious creation of a massive classification of nonstatus alien beneficiaries,” Mr. Hethmon wrote in his high court brief.

A decision that favors Texas would unravel opportunities for undocumented immigrants and prevent their ability to contribute to society, said Ignacia Rodriguez, a legal fellow at the National Immigration Law Center, which authored a brief in support of the government.

“What’s at stake is providing a stable environment for U.S. citizen children to grow, and providing people with the opportunity and tools to be able to contribute to the workforce [and] to the economy,” she said in an interview. “This is a payoff for everybody, not just those receiving the benefit.”

Regardless of what the Supreme Court decides, the next president could have the last word, according Ashley C. Parrish, a Washington D.C. attorney who cowrote a brief in support of the states. Mr. Parrish takes no position on the merits of the immigration programs, but rather, he is concerned with the administration’s failure to follow the Administrative Procedure Act’s requirements for notice-and-comment rule making.

“If the program were adopted as a legal rule after notice and comment, it could not be changed without going through a new notice-and-comment process,” he said. “If it is just a bare statement of policy, it can be changed at any time, without notice to anyone. The next administration could say, ‘Thank you for coming out of the shadows; we are now going to deport all of you.’ ”

Among the Democrats running for president, former Secretary of State Hillary Clinton has said she will defend DACA and Sen. Bernie Sanders (I-Vt.) has said he supports DACA and DAPA, and plans to expand them if elected.

Conversely, presumed Republican presidential nominee Donald Trump has indicated he would rescind DACA and related programs if elected.

After spending most of her life terrified of deportation, Ms. Rojas Marquez said she is not wasting time worrying about the Supreme Court’s decision or whether the next president will overturn the policy. She is keeping her studies foremost in her mind and the goal of becoming a doctor firmly in her heart.

“I have always lived with what-ifs,” she said. “This time around, I’m not going to be living in fear of the removing of DACA, because I wouldn’t have made it this far if I always lived in fear. My plan is no matter what happens, I’m going to finish medical school, and from there, I pray that I will be able to practice in the U.S.”

The Supreme Court is expected to issue its decision by June.

[email protected]

On Twitter @legal_med

Growing up, Denisse Rojas Marquez rarely visited the doctor. As undocumented immigrants from Mexico, her family viewed medical care as a luxury and sought it only in emergencies.

“I would always wait until it was very severe to see a doctor,” said Ms. Rojas Marquez, who came to the United States as a toddler. “That’s still a mentality I have to train myself out of. Growing up, going to the doctor meant very expensive bills and navigating through very complex systems.”

At 26, Ms. Rojas Marquez is determined to become a physician and help bridge the gap between undocumented immigrants and medical care. She is close to making that dream a reality because of a 2012 policy called the Deferred Action for Childhood Arrivals (DACA), which protects undocumented immigrants brought to the United States as children from deportation and offers access to work authorization. The policy enabled Ms. Rojas Marquez to become one of the first undocumented students to attend the Icahn School of Medicine at Mount Sinai in New York.

Photo provided by Denisse Rojas

But the fate of Ms. Rojas Marquez’s medical education is in flux as the U.S. Supreme Court considers protections for undocumented immigrants in the case of Texas v. United States. In dispute is the constitutionality of two of President Obama’s immigration policies: the Deferred Action for Parents of Americans and Lawful Permanent Residents (DAPA) and expanded DACA. The former protects undocumented immigrants who are parents of U.S. citizens from deportation, if they meet certain criteria. The second extends work authorization under the original DACA program from 2 years to 3 years and broadens age requirements.

Texas and 25 other states have sued over the programs, arguing the president does not have the authority to issue the new immigration policies, and that the programs violate the Constitution as well as the Administrative Procedure Act for notice-and-comment rule making. High court justices heard oral arguments April 18.

The ruling could impact the growing number of medical students with DACA status across the country, and jeopardize the funding invested in their training. Sixty-one medical schools now accept applications from DACA applicants, according to data from the Association of American Medical Colleges (AAMC). In 2015, 46 students with DACA status applied to U.S. medical schools and 20 were enrolled. In 2016, more than double (112) applied, although enrollment data will not be available until year’s end. Neither AAMC nor the National Resident Matching Program collect data on residents with DACA status.

A high court ruling in favor of the states could lead to DACA’s undoing, said Michael M. Hethmon, an attorney for the Immigration Reform Law Institute in Washington, D.C. The institute issued a brief to the Supreme Court in support of Texas.

If Texas prevails, “it’ll be a matter of weeks before a similar challenge will be levied against DACA and a number of other related programs,” Mr. Hethmon said in an interview. “There will be no more legal justification for those programs that exist.”

Saving talent or wasting money?

Loyola University in Chicago has accepted more students with DACA status than any other U.S. medical school. The reasons are simple, said Mark Kuczewski, Ph.D., chair of medical education at Loyola’s Stritch School of Medicine.

“We’re in the business of taking outstanding students,” Dr. Kuczewski said in an interview. “If the student is outstanding, we want them in our applicant pool. Second, being bilingual and bicultural is extremely important. We have patient populations out there that are diverse and underserved. We want to utilize this talent.”

In the fall of 2014, Stritch enrolled seven medical students with DACA status; in 2014, they doubled that enrollment. The students competed on the same playing field as other applicants and received no special treatment, Dr. Kuczewski said.

DACA students do pose funding challenges, he acknowledged. Although the students are protected from deportation and receive work authorization, they don’t qualify for federal student loans. Medical schools must find unique ways to help DACA students finance their education. A major Catholic health system provides student loan packages for several DACA students at Stritch, Dr. Kuczewski said. DACA students can also apply for financial assistance through an AAMC assistance program.

Abhinav Janghala

“Medical students use copious amounts of federal student loans,” he said. “Somehow the school has to make up that difference. We’ve found partners, but they don’t have infinite capacity, so we have to keep going back and finding new partners each year.”

The University of California, San Francisco, also has opened its doors to DACA students. Now in his third year, Jirayut New Latthivongskorn is UCSF’s first undocumented medical student. His education is financed by grants, private funding, and donations, said Mr. Latthivongskorn who came to the United States from Thailand when he was 9 years old. He is cofounder of Pre-Health Dreamers, a network of undocumented students who plan to pursue medical careers.

Before DACA granted his entry into UCSF, Mr. Latthivongskorn was accustomed to barriers because of his undocumented status, including having to turn down a nearly full-ride scholarship from the University of California, Davis, after high school.

“It was devastating,” Mr. Latthivongskorn said in an interview. “It was one of the very first times where I felt different and thought, ‘This is not going to work. You are undocumented.’”

Mr. Latthivongskorn and his family scraped together money for him to complete his undergraduate degree at the University of California, Berkeley. California has since passed the DREAM Act, a law that allows undocumented immigrants to receive private scholarships funded through public universities.

Not everyone believes undocumented immigrants should get the chance to become U.S. physicians. Dr. Jane M. Orient, executive director of the Association of American Physicians and Surgeons, argued that undocumented immigrants are not the answer to curbing the physician shortage.

“In a country that’s supposed to be ruled by law, it seems incomprehensible that people who are violating the law should be given privileges over people who are here legally,” she said in an interview. “We desperately do need more physicians, but we should not be blocking Americans from having this opportunity.”

Dr. Shirie Leng, a Boston anesthesiologist, said DACA is promising in theory, but falls short in practical application.

“There’s no particular reason why [undocumented students] wouldn’t make great doctors,” said Dr. Leng. “The problem is funding related. You can give kids all the opportunity you want, but if you can’t pay for it, that seems to me to be the biggest sticking point.”

Basing admission policies on programs that are vulnerable could end poorly for schools and students, Dr. Leng added.

If DACA is revoked, “it’s not just a waste of money for the school, but a waste of time for the kids,” she said.

Protections hinge on Supreme Court … and next president

During oral arguments earlier this month, justices appeared to disagree on whether DAPA and expanded DACA were properly executed.

Associate Justice Anthony M. Kennedy indicated that the normal order of government policy making had been “turned upside down,” by the creation of the programs. Associate Justice Sonia Sotomayor, meanwhile, noted that immigration policies with broader reaches have been similarly instituted in the past.

A ruling for the government would mean the president can use his executive power to enact policies that run contrary to immigration laws already in place, said Mr. Hethmon, the D.C. attorney. Current immigration laws trump informal agency discretion and do not allow for the government’s “arbitrary and capricious creation of a massive classification of nonstatus alien beneficiaries,” Mr. Hethmon wrote in his high court brief.

A decision that favors Texas would unravel opportunities for undocumented immigrants and prevent their ability to contribute to society, said Ignacia Rodriguez, a legal fellow at the National Immigration Law Center, which authored a brief in support of the government.

“What’s at stake is providing a stable environment for U.S. citizen children to grow, and providing people with the opportunity and tools to be able to contribute to the workforce [and] to the economy,” she said in an interview. “This is a payoff for everybody, not just those receiving the benefit.”

Regardless of what the Supreme Court decides, the next president could have the last word, according Ashley C. Parrish, a Washington D.C. attorney who cowrote a brief in support of the states. Mr. Parrish takes no position on the merits of the immigration programs, but rather, he is concerned with the administration’s failure to follow the Administrative Procedure Act’s requirements for notice-and-comment rule making.

“If the program were adopted as a legal rule after notice and comment, it could not be changed without going through a new notice-and-comment process,” he said. “If it is just a bare statement of policy, it can be changed at any time, without notice to anyone. The next administration could say, ‘Thank you for coming out of the shadows; we are now going to deport all of you.’ ”

Among the Democrats running for president, former Secretary of State Hillary Clinton has said she will defend DACA and Sen. Bernie Sanders (I-Vt.) has said he supports DACA and DAPA, and plans to expand them if elected.

Conversely, presumed Republican presidential nominee Donald Trump has indicated he would rescind DACA and related programs if elected.

After spending most of her life terrified of deportation, Ms. Rojas Marquez said she is not wasting time worrying about the Supreme Court’s decision or whether the next president will overturn the policy. She is keeping her studies foremost in her mind and the goal of becoming a doctor firmly in her heart.

“I have always lived with what-ifs,” she said. “This time around, I’m not going to be living in fear of the removing of DACA, because I wouldn’t have made it this far if I always lived in fear. My plan is no matter what happens, I’m going to finish medical school, and from there, I pray that I will be able to practice in the U.S.”

The Supreme Court is expected to issue its decision by June.

[email protected]

On Twitter @legal_med

Growing up, Denisse Rojas Marquez rarely visited the doctor. As undocumented immigrants from Mexico, her family viewed medical care as a luxury and sought it only in emergencies.

“I would always wait until it was very severe to see a doctor,” said Ms. Rojas Marquez, who came to the United States as a toddler. “That’s still a mentality I have to train myself out of. Growing up, going to the doctor meant very expensive bills and navigating through very complex systems.”

At 26, Ms. Rojas Marquez is determined to become a physician and help bridge the gap between undocumented immigrants and medical care. She is close to making that dream a reality because of a 2012 policy called the Deferred Action for Childhood Arrivals (DACA), which protects undocumented immigrants brought to the United States as children from deportation and offers access to work authorization. The policy enabled Ms. Rojas Marquez to become one of the first undocumented students to attend the Icahn School of Medicine at Mount Sinai in New York.

Photo provided by Denisse Rojas

But the fate of Ms. Rojas Marquez’s medical education is in flux as the U.S. Supreme Court considers protections for undocumented immigrants in the case of Texas v. United States. In dispute is the constitutionality of two of President Obama’s immigration policies: the Deferred Action for Parents of Americans and Lawful Permanent Residents (DAPA) and expanded DACA. The former protects undocumented immigrants who are parents of U.S. citizens from deportation, if they meet certain criteria. The second extends work authorization under the original DACA program from 2 years to 3 years and broadens age requirements.

Texas and 25 other states have sued over the programs, arguing the president does not have the authority to issue the new immigration policies, and that the programs violate the Constitution as well as the Administrative Procedure Act for notice-and-comment rule making. High court justices heard oral arguments April 18.

The ruling could impact the growing number of medical students with DACA status across the country, and jeopardize the funding invested in their training. Sixty-one medical schools now accept applications from DACA applicants, according to data from the Association of American Medical Colleges (AAMC). In 2015, 46 students with DACA status applied to U.S. medical schools and 20 were enrolled. In 2016, more than double (112) applied, although enrollment data will not be available until year’s end. Neither AAMC nor the National Resident Matching Program collect data on residents with DACA status.

A high court ruling in favor of the states could lead to DACA’s undoing, said Michael M. Hethmon, an attorney for the Immigration Reform Law Institute in Washington, D.C. The institute issued a brief to the Supreme Court in support of Texas.

If Texas prevails, “it’ll be a matter of weeks before a similar challenge will be levied against DACA and a number of other related programs,” Mr. Hethmon said in an interview. “There will be no more legal justification for those programs that exist.”

Saving talent or wasting money?

Loyola University in Chicago has accepted more students with DACA status than any other U.S. medical school. The reasons are simple, said Mark Kuczewski, Ph.D., chair of medical education at Loyola’s Stritch School of Medicine.

“We’re in the business of taking outstanding students,” Dr. Kuczewski said in an interview. “If the student is outstanding, we want them in our applicant pool. Second, being bilingual and bicultural is extremely important. We have patient populations out there that are diverse and underserved. We want to utilize this talent.”

In the fall of 2014, Stritch enrolled seven medical students with DACA status; in 2014, they doubled that enrollment. The students competed on the same playing field as other applicants and received no special treatment, Dr. Kuczewski said.

DACA students do pose funding challenges, he acknowledged. Although the students are protected from deportation and receive work authorization, they don’t qualify for federal student loans. Medical schools must find unique ways to help DACA students finance their education. A major Catholic health system provides student loan packages for several DACA students at Stritch, Dr. Kuczewski said. DACA students can also apply for financial assistance through an AAMC assistance program.

Abhinav Janghala

“Medical students use copious amounts of federal student loans,” he said. “Somehow the school has to make up that difference. We’ve found partners, but they don’t have infinite capacity, so we have to keep going back and finding new partners each year.”

The University of California, San Francisco, also has opened its doors to DACA students. Now in his third year, Jirayut New Latthivongskorn is UCSF’s first undocumented medical student. His education is financed by grants, private funding, and donations, said Mr. Latthivongskorn who came to the United States from Thailand when he was 9 years old. He is cofounder of Pre-Health Dreamers, a network of undocumented students who plan to pursue medical careers.

Before DACA granted his entry into UCSF, Mr. Latthivongskorn was accustomed to barriers because of his undocumented status, including having to turn down a nearly full-ride scholarship from the University of California, Davis, after high school.

“It was devastating,” Mr. Latthivongskorn said in an interview. “It was one of the very first times where I felt different and thought, ‘This is not going to work. You are undocumented.’”

Mr. Latthivongskorn and his family scraped together money for him to complete his undergraduate degree at the University of California, Berkeley. California has since passed the DREAM Act, a law that allows undocumented immigrants to receive private scholarships funded through public universities.

Not everyone believes undocumented immigrants should get the chance to become U.S. physicians. Dr. Jane M. Orient, executive director of the Association of American Physicians and Surgeons, argued that undocumented immigrants are not the answer to curbing the physician shortage.

“In a country that’s supposed to be ruled by law, it seems incomprehensible that people who are violating the law should be given privileges over people who are here legally,” she said in an interview. “We desperately do need more physicians, but we should not be blocking Americans from having this opportunity.”

Dr. Shirie Leng, a Boston anesthesiologist, said DACA is promising in theory, but falls short in practical application.

“There’s no particular reason why [undocumented students] wouldn’t make great doctors,” said Dr. Leng. “The problem is funding related. You can give kids all the opportunity you want, but if you can’t pay for it, that seems to me to be the biggest sticking point.”

Basing admission policies on programs that are vulnerable could end poorly for schools and students, Dr. Leng added.

If DACA is revoked, “it’s not just a waste of money for the school, but a waste of time for the kids,” she said.

Protections hinge on Supreme Court … and next president

During oral arguments earlier this month, justices appeared to disagree on whether DAPA and expanded DACA were properly executed.

Associate Justice Anthony M. Kennedy indicated that the normal order of government policy making had been “turned upside down,” by the creation of the programs. Associate Justice Sonia Sotomayor, meanwhile, noted that immigration policies with broader reaches have been similarly instituted in the past.

A ruling for the government would mean the president can use his executive power to enact policies that run contrary to immigration laws already in place, said Mr. Hethmon, the D.C. attorney. Current immigration laws trump informal agency discretion and do not allow for the government’s “arbitrary and capricious creation of a massive classification of nonstatus alien beneficiaries,” Mr. Hethmon wrote in his high court brief.

A decision that favors Texas would unravel opportunities for undocumented immigrants and prevent their ability to contribute to society, said Ignacia Rodriguez, a legal fellow at the National Immigration Law Center, which authored a brief in support of the government.

“What’s at stake is providing a stable environment for U.S. citizen children to grow, and providing people with the opportunity and tools to be able to contribute to the workforce [and] to the economy,” she said in an interview. “This is a payoff for everybody, not just those receiving the benefit.”

Regardless of what the Supreme Court decides, the next president could have the last word, according Ashley C. Parrish, a Washington D.C. attorney who cowrote a brief in support of the states. Mr. Parrish takes no position on the merits of the immigration programs, but rather, he is concerned with the administration’s failure to follow the Administrative Procedure Act’s requirements for notice-and-comment rule making.

“If the program were adopted as a legal rule after notice and comment, it could not be changed without going through a new notice-and-comment process,” he said. “If it is just a bare statement of policy, it can be changed at any time, without notice to anyone. The next administration could say, ‘Thank you for coming out of the shadows; we are now going to deport all of you.’ ”

Among the Democrats running for president, former Secretary of State Hillary Clinton has said she will defend DACA and Sen. Bernie Sanders (I-Vt.) has said he supports DACA and DAPA, and plans to expand them if elected.

Conversely, presumed Republican presidential nominee Donald Trump has indicated he would rescind DACA and related programs if elected.

After spending most of her life terrified of deportation, Ms. Rojas Marquez said she is not wasting time worrying about the Supreme Court’s decision or whether the next president will overturn the policy. She is keeping her studies foremost in her mind and the goal of becoming a doctor firmly in her heart.

“I have always lived with what-ifs,” she said. “This time around, I’m not going to be living in fear of the removing of DACA, because I wouldn’t have made it this far if I always lived in fear. My plan is no matter what happens, I’m going to finish medical school, and from there, I pray that I will be able to practice in the U.S.”

The Supreme Court is expected to issue its decision by June.

[email protected]

On Twitter @legal_med

Chronic anticoagulation is a common preex­isting condition in patients undergoing total joint arthroplasty (TJA). Atrial fibrillation (AF), the most common underlying disorder requiring chronic anticoagulation, affects more than 3 million patients in the United States—a number that is projected to increase to 16 million by 2050.^1,2 Other common indications for anticoagulation are deep vein thrombosis (DVT) treatment, presence of a prosthetic heart valve, and venous thromboembolism (VTE) prevention after hip or knee arthroplasty. These patients face the additional risks of hemorrhage, persistent wound drainage, hematoma formation, transfusion requirements, periprosthetic joint infection, and longer hospital stay.¹ Chronic anticoagulation traditionally has been managed with warfarin, which inhibits production of the vitamin K–dependent clotting factors II, VII, IX, and X. However, the new novel oral anticoagulants (NOACs), which target individual factors in the clotting cascade, are gaining favor as chronic anticoagulant agents because of their ease of use and improved efficacy and safety. These agents include the factor IIA inhibitor dabigatran (Pradaxa) and the direct factor Xa inhibitors rivaroxaban (Xarelto) and apixaban (Eliquis).

Management of patients at risk for thromboembolism and bleeding issues, particularly within the context of elective, urgent, or emergent orthopedic surgeries, is an evolving area. Understanding the pharmacokinetics, conventional laboratory tests, dosing, and reversal methods for NOACs is important, especially because clinical data are limited and the treatment itself can cause clinically significant harm.

In this article, we review the medical literature on these medications, their mechanism of action, and their reversal agents, and outline a practical approach for managing patients during the perioperative period.

Dabigatran

In October 2010, dabigatran became the first NOAC approved by the US Food and Drug Administration (FDA) for the prevention of arterial thromboembolic events in patients with nonvalvular AF, on the basis of the results of the RELY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial. Dabigatran is an oral factor IIA (thrombin) inhibitor. From time of ingestion, dabigatran takes 1.25 to 3 hours to reach peak plasma concentration. It has a half-life of 12 to 14 hours, is excreted predominantly by the kidneys (80%), and is renally dosed. The usual dose is 150 mg 2 times daily if creatinine clearance (CrCl) is >30 mL/minute, or 75 mg 2 times daily if CrCl is 15 to 30 mL/minute.³ Dabigatran is not recommended for patients with CrCl <15 mL/minute.

Dabigatran affects prothrombin time (PT), activated partial thromboplastin time (aPTT), ecarin clotting time, and thrombin time, with the latter 2 providing the most accurate means of monitoring appropriate drug levels.^3,4 Of the tests commonly used to assess coagulation hemostasis in hospitals, normalization of thrombin time and aPTT provide the most accurate results (Table 1). The pharmacokinetics of dabigatran mandate consideration of dose, time of ingestion relative to time of blood sampling, and renal function in the assessment of coagulation hemostasis.

For elective surgeries, the periprocedure recommendation for patients being treated with dabigatran is to discontinue the medication 3 to 4 days before an operation if CrCl is ≥50 mL/minute, or 4 to 5 days beforehand if CrCl is <50 mL/minute.³ There is no antidote for dabigatran. In an in vitro model, activated charcoal reduced 99.9% of dabigatran absorption after recent ingestion.³ According to case reports, acute hemodialysis successfully removed 60% of the medication after 6 hours.⁵ In patients with end-stage renal disease, hemodialysis removed up to 68% of active dabigatran after 4 hours.³

Pernod and colleagues6 proposed that urgent surgeries can proceed if the concentration of dabigatran is ≤30 ng/mL—equivalent to normal aPTT. Their dictum was extrapolated from the data of patients who underwent elective surgeries while being treated with dabigatran, as recorded during the RELY trial. According to Pernod and colleagues,⁶ if aPTT is increased (probable drug level, ≥30 ng/mL), surgery should be postponed for up to 12 hours, with aPTT checked again and the process repeated if the concentration of dabigatran is still elevated and surgery can continue to be delayed. In patients who require urgent surgical interventions, we previously utilized nanofiltered activated prothrombin complex concentrate (aPCC; Feiba NF) 30 to 50 IU/kg over prothrombin complex concentrate (PCC; Kcentra or Bebulin) 25 to 50 IU/kg, as supported by in vitro and animal model studies and anecdotal case reports. However, neither aPCC nor PCC fully corrects the abnormalities evident on hemostasis tests.3,6 In October 2015, the FDA approved Idarucizumab (Praxbind), an injectable monoclonal antibody fragment that binds to dabigatran, as a reversing agent for use in urgent/emergent settings. Recommendation is to administer two 50-ml bolus infusions, each containing 2.5 g of idarucizumab, no more than 15 minutes apart.⁷ Additionally, hemodialysis could be discussed before surgery, with the understanding that it will take a long time to reach the threshold of 30 ng/mL in these patients (Table 2).

Rivaroxaban

Rivaroxaban is an oral direct factor Xa inhibitor that was initially approved in November 2011 for the prevention of stroke and systemic embolism in patients with nonvalvular AF. Since then, clinical use of rivaroxaban has been expanded to include prevention of VTE after elective hip or knee arthroplasty as well as treatment of DVT and prevention of recurrent VTE after acute DVT. In the phase 3 ROCKET AF (Rivaroxaban Once-Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) study, rivaroxaban 20 mg daily (CrCl, ≥50 mL/min) and rivaroxaban 15 mg daily (CrCl, 15-49 mL/min) were equally effective as warfarin. Compared with warfarin, rivaroxaban had a similar safety rate for bleeding and adverse events but fewer intracranial hemorrhage and fatal bleeding events.⁸ On the basis of the outcomes of the RECORD (Regulation of Coagulation in Orthopedic Surgery to Prevent Deep Venous Thrombosis and Pulmonary Embolism) studies comparing rivaroxaban and enoxaparin sodium, rivaroxaban 10 mg daily was approved for the prevention of VTE and pulmonary embolism after elective hip or knee arthroplasty.⁸

The half-life of rivaroxaban is 5 to 9 hours in the young and 11 to 13 hours in the elderly.⁸ As rivaroxaban takes 2 to 4 hours after ingestion to reach peak plasma concentration, it is important to know the timing and the dose taken. Because of the short half-life and rapid onset of action of this medication, bridging with another anticoagulant is not required when rivaroxaban is discontinued before surgery or initiated after surgery.⁸ The recommendation is to withhold rivaroxaban for 24 to 48 hours before surgery and then to administer the first postoperative dose 6 to 10 hours after surgery, or when hemostasis is achieved (Table 1).

PT is recommended for rivaroxaban detection. Conventional assays are not sensitive at low concentrations, and degree of prolongation does not reliably predict amount of medication present.^3,9 However, normal PT corresponds to a drug concentration of about 30 ng/mL and is considered safe for patients undergoing surgical intervention without increased risk for bleeding.⁶ This recommendation was extrapolated from data in the ROCKET AF study of patients who underwent elective surgeries while on rivaroxaban.⁶ Commercially available chromogenic anti–factor Xa assays, used with a rivaroxaban calibration curve, are sensitive and specific for rivaroxaban plasma concentrations.^3,8 However, these assays are not widely available.

If a bleeding complication occurs in a patient who is being treated with rivaroxaban, the next rivaroxaban dose should be delayed, or treatment should be discontinued, as appropriate.⁸ Urgency of surgery should be weighed against risk for bleeding complications on a case-by-case basis. This decision is deferred to the clinical judgment of the surgeon. In the case of a patient with severe, life-threatening bleeding or a patient who requires emergent surgery, PCC 25-50 IU/kg is the recommended reversal agent.⁹ Recombinant factor VIIa and aPCC have been used in experimental settings, but there is concern about the greater prothrombotic potential of these agents compared with PCC⁸ (Table 2).

Apixaban

Apixaban is the second factor Xa inhibitor introduced in the United States and the first to show—in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) study—efficacy superior to that of warfarin for the prevention of stroke and systemic embolism, all-cause mortality, and major bleeding. Furthermore, in the AVERROES (Apixaban Versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment) study, apixaban used in AF patients who were deemed not suitable for warfarin proved to be more effective than aspirin for stroke prevention, and had a similar rate of major bleeding.¹⁰ Apixaban is administered in a 5-mg dose 2 times daily. It has a half-life of 10 to 14 hours, is highly protein-bound, and has predominantly fecal excretion (27% is renal). Apixaban can prolong PT, but the correlation is nonlinear. Barrett and colleagues¹¹ found that chromogenic anti–factor Xa assays provided the most accurate readings of apixaban plasma concentrations. Normal anti–factor Xa activity in patients being treated with apixaban suggests low drug levels and an intact hemostatic function, which are indicators of low bleeding risk with surgical intervention³ (Table 1).

Similar to other NOACs, apixaban has no antidote. In vitro testing showed that PCC improved thrombin generation when added to the blood of healthy donors who had received apixaban. Despite the lack of clinical experience, use of PCC 50 IU/kg may be reasonable for apixaban patients with severe or life-threatening bleeding³ (Table 2). Unlike dabigatran, apixaban cannot be eliminated with dialysis because of its high degree of protein binding. In nonemergent circumstances, delaying surgery 24 to 48 hours is considered effective in reducing the concentration of apixaban to a range that does not cause additional risk for bleeding.

Conclusion

Compared with warfarin, the NOACs dabigatran, rivaroxaban, and apixaban are efficacious and safe. Because of their steady pharmacokinetics, they do not require regular coagulation testing, as is the case with warfarin. These NOACs have been approved for the prevention of stroke and thromboembolic events in patients with nonvalvular AF; rivaroxaban has also been approved for VTE prevention after total hip or knee arthroplasty, for DVT treatment, and for prevention of recurrent VTE after acute DVT. Other options for VTE prophylaxis after hip and knee surgery are addressed in the guidelines issued by the American Academy of Orthopaedic Surgeons in 2011.¹² As the incidence of chronic anticoagulation continues to increase among patients undergoing TJA, orthopedic surgeons need to be aware of the mechanism of action of these NOACs, as well as their pharmacokinetics and available reversal agents. Aggarwal and colleagues1 found that AF patients undergoing TJA had longer hospital stays, increased transfusion requirements, and increased risk for periprosthetic joint infection and unplanned hospital readmission.

The anticoagulation tests recommended for evaluation of hemostasis and drug reversal are normalization of aPTT for dabigatran; PT for rivaroxaban; and chromogenic anti–factor Xa activity for apixaban³ (Table 2). Although several research projects are being planned to develop an antidote for these medications, no antidote has been approved for human trials. The coagulation agents currently being used for reversal of NOACs are nonactivated PCC (Kcentra, Bebulin) and aPCC. Kcentra is a 4-factor PCC (II, VII, IX, X), and Bebulin is a 3-factor PCC (II, IX, X). Most authors recommend using 4-factor PCC 25 to 50 IU/kg. In vivo studies and animal studies have shown that nanofiltered aPCC (Feiba NF) at doses of 30 to 50 IU/kg can to some extent reverse anticoagulation in patients receiving NOACs. The current, limited data support use of reversal agent PCC for rivaroxaban and apixaban (no human studies for apixaban) and use of aPCC for dabigatran.^3,6,8 Activated charcoal can be used for patients who have taken dabigatran <6 hours before presentation.³ Hemodialysis is another option for dabigatran removal. Hemodialysis, however, takes 4 to 6 hours or longer to remove about 60% of the medication (Table 2).^3,5

In major orthopedic surgeries, such as TJA, bleeding is a critical concern. Using reversal agents to overcome the anticoagulation effect adds to the potential concern for thromboembolism secondary to these agents. Therefore, in cases in which surgery cannot be delayed any longer, the decision to use reversal agents should be made on a case-by-case basis. For most patients on rivaroxaban or apixaban, it is sufficient to delay for 24 to 48 hours before proceeding safely with surgery; for dabigatran, a delay of 3 to 4 days is recommended. Delay before surgery may need to be extended for the elderly and for patients with renal failure. The pharmacokinetics of these medications is summarized in Table 1.

There are no guidelines for perioperative management of patients undergoing elective, urgent, or emergent surgeries while on NOACs. As discussed, Pernod and colleagues6 proposed better perioperative management of major bleeding risks in patients receiving rivaroxaban or dabigatran. Adapting their approach, and using the data available from the medical literature, we propose a perioperative algorithm that can guide practicing orthopedic surgeons performing urgent and emergent surgeries (Figure).

The population of patients receiving chronic anticoagulation therapy is growing, and anticoagulant and antiplatelet options are increasing in the United States and around the world. We propose a team approach for patient care, with orthopedic surgeon and cardiologist or vascular medicine specialist collaborating to ensure the safety and effectiveness of this treatment.

Chronic anticoagulation is a common preex­isting condition in patients undergoing total joint arthroplasty (TJA). Atrial fibrillation (AF), the most common underlying disorder requiring chronic anticoagulation, affects more than 3 million patients in the United States—a number that is projected to increase to 16 million by 2050.^1,2 Other common indications for anticoagulation are deep vein thrombosis (DVT) treatment, presence of a prosthetic heart valve, and venous thromboembolism (VTE) prevention after hip or knee arthroplasty. These patients face the additional risks of hemorrhage, persistent wound drainage, hematoma formation, transfusion requirements, periprosthetic joint infection, and longer hospital stay.¹ Chronic anticoagulation traditionally has been managed with warfarin, which inhibits production of the vitamin K–dependent clotting factors II, VII, IX, and X. However, the new novel oral anticoagulants (NOACs), which target individual factors in the clotting cascade, are gaining favor as chronic anticoagulant agents because of their ease of use and improved efficacy and safety. These agents include the factor IIA inhibitor dabigatran (Pradaxa) and the direct factor Xa inhibitors rivaroxaban (Xarelto) and apixaban (Eliquis).

Management of patients at risk for thromboembolism and bleeding issues, particularly within the context of elective, urgent, or emergent orthopedic surgeries, is an evolving area. Understanding the pharmacokinetics, conventional laboratory tests, dosing, and reversal methods for NOACs is important, especially because clinical data are limited and the treatment itself can cause clinically significant harm.

In this article, we review the medical literature on these medications, their mechanism of action, and their reversal agents, and outline a practical approach for managing patients during the perioperative period.

Dabigatran

In October 2010, dabigatran became the first NOAC approved by the US Food and Drug Administration (FDA) for the prevention of arterial thromboembolic events in patients with nonvalvular AF, on the basis of the results of the RELY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial. Dabigatran is an oral factor IIA (thrombin) inhibitor. From time of ingestion, dabigatran takes 1.25 to 3 hours to reach peak plasma concentration. It has a half-life of 12 to 14 hours, is excreted predominantly by the kidneys (80%), and is renally dosed. The usual dose is 150 mg 2 times daily if creatinine clearance (CrCl) is >30 mL/minute, or 75 mg 2 times daily if CrCl is 15 to 30 mL/minute.³ Dabigatran is not recommended for patients with CrCl <15 mL/minute.

Dabigatran affects prothrombin time (PT), activated partial thromboplastin time (aPTT), ecarin clotting time, and thrombin time, with the latter 2 providing the most accurate means of monitoring appropriate drug levels.^3,4 Of the tests commonly used to assess coagulation hemostasis in hospitals, normalization of thrombin time and aPTT provide the most accurate results (Table 1). The pharmacokinetics of dabigatran mandate consideration of dose, time of ingestion relative to time of blood sampling, and renal function in the assessment of coagulation hemostasis.

For elective surgeries, the periprocedure recommendation for patients being treated with dabigatran is to discontinue the medication 3 to 4 days before an operation if CrCl is ≥50 mL/minute, or 4 to 5 days beforehand if CrCl is <50 mL/minute.³ There is no antidote for dabigatran. In an in vitro model, activated charcoal reduced 99.9% of dabigatran absorption after recent ingestion.³ According to case reports, acute hemodialysis successfully removed 60% of the medication after 6 hours.⁵ In patients with end-stage renal disease, hemodialysis removed up to 68% of active dabigatran after 4 hours.³

Pernod and colleagues6 proposed that urgent surgeries can proceed if the concentration of dabigatran is ≤30 ng/mL—equivalent to normal aPTT. Their dictum was extrapolated from the data of patients who underwent elective surgeries while being treated with dabigatran, as recorded during the RELY trial. According to Pernod and colleagues,⁶ if aPTT is increased (probable drug level, ≥30 ng/mL), surgery should be postponed for up to 12 hours, with aPTT checked again and the process repeated if the concentration of dabigatran is still elevated and surgery can continue to be delayed. In patients who require urgent surgical interventions, we previously utilized nanofiltered activated prothrombin complex concentrate (aPCC; Feiba NF) 30 to 50 IU/kg over prothrombin complex concentrate (PCC; Kcentra or Bebulin) 25 to 50 IU/kg, as supported by in vitro and animal model studies and anecdotal case reports. However, neither aPCC nor PCC fully corrects the abnormalities evident on hemostasis tests.3,6 In October 2015, the FDA approved Idarucizumab (Praxbind), an injectable monoclonal antibody fragment that binds to dabigatran, as a reversing agent for use in urgent/emergent settings. Recommendation is to administer two 50-ml bolus infusions, each containing 2.5 g of idarucizumab, no more than 15 minutes apart.⁷ Additionally, hemodialysis could be discussed before surgery, with the understanding that it will take a long time to reach the threshold of 30 ng/mL in these patients (Table 2).

Rivaroxaban

Rivaroxaban is an oral direct factor Xa inhibitor that was initially approved in November 2011 for the prevention of stroke and systemic embolism in patients with nonvalvular AF. Since then, clinical use of rivaroxaban has been expanded to include prevention of VTE after elective hip or knee arthroplasty as well as treatment of DVT and prevention of recurrent VTE after acute DVT. In the phase 3 ROCKET AF (Rivaroxaban Once-Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) study, rivaroxaban 20 mg daily (CrCl, ≥50 mL/min) and rivaroxaban 15 mg daily (CrCl, 15-49 mL/min) were equally effective as warfarin. Compared with warfarin, rivaroxaban had a similar safety rate for bleeding and adverse events but fewer intracranial hemorrhage and fatal bleeding events.⁸ On the basis of the outcomes of the RECORD (Regulation of Coagulation in Orthopedic Surgery to Prevent Deep Venous Thrombosis and Pulmonary Embolism) studies comparing rivaroxaban and enoxaparin sodium, rivaroxaban 10 mg daily was approved for the prevention of VTE and pulmonary embolism after elective hip or knee arthroplasty.⁸

The half-life of rivaroxaban is 5 to 9 hours in the young and 11 to 13 hours in the elderly.⁸ As rivaroxaban takes 2 to 4 hours after ingestion to reach peak plasma concentration, it is important to know the timing and the dose taken. Because of the short half-life and rapid onset of action of this medication, bridging with another anticoagulant is not required when rivaroxaban is discontinued before surgery or initiated after surgery.⁸ The recommendation is to withhold rivaroxaban for 24 to 48 hours before surgery and then to administer the first postoperative dose 6 to 10 hours after surgery, or when hemostasis is achieved (Table 1).

PT is recommended for rivaroxaban detection. Conventional assays are not sensitive at low concentrations, and degree of prolongation does not reliably predict amount of medication present.^3,9 However, normal PT corresponds to a drug concentration of about 30 ng/mL and is considered safe for patients undergoing surgical intervention without increased risk for bleeding.⁶ This recommendation was extrapolated from data in the ROCKET AF study of patients who underwent elective surgeries while on rivaroxaban.⁶ Commercially available chromogenic anti–factor Xa assays, used with a rivaroxaban calibration curve, are sensitive and specific for rivaroxaban plasma concentrations.^3,8 However, these assays are not widely available.

If a bleeding complication occurs in a patient who is being treated with rivaroxaban, the next rivaroxaban dose should be delayed, or treatment should be discontinued, as appropriate.⁸ Urgency of surgery should be weighed against risk for bleeding complications on a case-by-case basis. This decision is deferred to the clinical judgment of the surgeon. In the case of a patient with severe, life-threatening bleeding or a patient who requires emergent surgery, PCC 25-50 IU/kg is the recommended reversal agent.⁹ Recombinant factor VIIa and aPCC have been used in experimental settings, but there is concern about the greater prothrombotic potential of these agents compared with PCC⁸ (Table 2).

Apixaban

Apixaban is the second factor Xa inhibitor introduced in the United States and the first to show—in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) study—efficacy superior to that of warfarin for the prevention of stroke and systemic embolism, all-cause mortality, and major bleeding. Furthermore, in the AVERROES (Apixaban Versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment) study, apixaban used in AF patients who were deemed not suitable for warfarin proved to be more effective than aspirin for stroke prevention, and had a similar rate of major bleeding.¹⁰ Apixaban is administered in a 5-mg dose 2 times daily. It has a half-life of 10 to 14 hours, is highly protein-bound, and has predominantly fecal excretion (27% is renal). Apixaban can prolong PT, but the correlation is nonlinear. Barrett and colleagues¹¹ found that chromogenic anti–factor Xa assays provided the most accurate readings of apixaban plasma concentrations. Normal anti–factor Xa activity in patients being treated with apixaban suggests low drug levels and an intact hemostatic function, which are indicators of low bleeding risk with surgical intervention³ (Table 1).

Similar to other NOACs, apixaban has no antidote. In vitro testing showed that PCC improved thrombin generation when added to the blood of healthy donors who had received apixaban. Despite the lack of clinical experience, use of PCC 50 IU/kg may be reasonable for apixaban patients with severe or life-threatening bleeding³ (Table 2). Unlike dabigatran, apixaban cannot be eliminated with dialysis because of its high degree of protein binding. In nonemergent circumstances, delaying surgery 24 to 48 hours is considered effective in reducing the concentration of apixaban to a range that does not cause additional risk for bleeding.

Conclusion

Compared with warfarin, the NOACs dabigatran, rivaroxaban, and apixaban are efficacious and safe. Because of their steady pharmacokinetics, they do not require regular coagulation testing, as is the case with warfarin. These NOACs have been approved for the prevention of stroke and thromboembolic events in patients with nonvalvular AF; rivaroxaban has also been approved for VTE prevention after total hip or knee arthroplasty, for DVT treatment, and for prevention of recurrent VTE after acute DVT. Other options for VTE prophylaxis after hip and knee surgery are addressed in the guidelines issued by the American Academy of Orthopaedic Surgeons in 2011.¹² As the incidence of chronic anticoagulation continues to increase among patients undergoing TJA, orthopedic surgeons need to be aware of the mechanism of action of these NOACs, as well as their pharmacokinetics and available reversal agents. Aggarwal and colleagues1 found that AF patients undergoing TJA had longer hospital stays, increased transfusion requirements, and increased risk for periprosthetic joint infection and unplanned hospital readmission.

The anticoagulation tests recommended for evaluation of hemostasis and drug reversal are normalization of aPTT for dabigatran; PT for rivaroxaban; and chromogenic anti–factor Xa activity for apixaban³ (Table 2). Although several research projects are being planned to develop an antidote for these medications, no antidote has been approved for human trials. The coagulation agents currently being used for reversal of NOACs are nonactivated PCC (Kcentra, Bebulin) and aPCC. Kcentra is a 4-factor PCC (II, VII, IX, X), and Bebulin is a 3-factor PCC (II, IX, X). Most authors recommend using 4-factor PCC 25 to 50 IU/kg. In vivo studies and animal studies have shown that nanofiltered aPCC (Feiba NF) at doses of 30 to 50 IU/kg can to some extent reverse anticoagulation in patients receiving NOACs. The current, limited data support use of reversal agent PCC for rivaroxaban and apixaban (no human studies for apixaban) and use of aPCC for dabigatran.^3,6,8 Activated charcoal can be used for patients who have taken dabigatran <6 hours before presentation.³ Hemodialysis is another option for dabigatran removal. Hemodialysis, however, takes 4 to 6 hours or longer to remove about 60% of the medication (Table 2).^3,5

In major orthopedic surgeries, such as TJA, bleeding is a critical concern. Using reversal agents to overcome the anticoagulation effect adds to the potential concern for thromboembolism secondary to these agents. Therefore, in cases in which surgery cannot be delayed any longer, the decision to use reversal agents should be made on a case-by-case basis. For most patients on rivaroxaban or apixaban, it is sufficient to delay for 24 to 48 hours before proceeding safely with surgery; for dabigatran, a delay of 3 to 4 days is recommended. Delay before surgery may need to be extended for the elderly and for patients with renal failure. The pharmacokinetics of these medications is summarized in Table 1.

There are no guidelines for perioperative management of patients undergoing elective, urgent, or emergent surgeries while on NOACs. As discussed, Pernod and colleagues6 proposed better perioperative management of major bleeding risks in patients receiving rivaroxaban or dabigatran. Adapting their approach, and using the data available from the medical literature, we propose a perioperative algorithm that can guide practicing orthopedic surgeons performing urgent and emergent surgeries (Figure).

The population of patients receiving chronic anticoagulation therapy is growing, and anticoagulant and antiplatelet options are increasing in the United States and around the world. We propose a team approach for patient care, with orthopedic surgeon and cardiologist or vascular medicine specialist collaborating to ensure the safety and effectiveness of this treatment.

Chronic anticoagulation is a common preex­isting condition in patients undergoing total joint arthroplasty (TJA). Atrial fibrillation (AF), the most common underlying disorder requiring chronic anticoagulation, affects more than 3 million patients in the United States—a number that is projected to increase to 16 million by 2050.^1,2 Other common indications for anticoagulation are deep vein thrombosis (DVT) treatment, presence of a prosthetic heart valve, and venous thromboembolism (VTE) prevention after hip or knee arthroplasty. These patients face the additional risks of hemorrhage, persistent wound drainage, hematoma formation, transfusion requirements, periprosthetic joint infection, and longer hospital stay.¹ Chronic anticoagulation traditionally has been managed with warfarin, which inhibits production of the vitamin K–dependent clotting factors II, VII, IX, and X. However, the new novel oral anticoagulants (NOACs), which target individual factors in the clotting cascade, are gaining favor as chronic anticoagulant agents because of their ease of use and improved efficacy and safety. These agents include the factor IIA inhibitor dabigatran (Pradaxa) and the direct factor Xa inhibitors rivaroxaban (Xarelto) and apixaban (Eliquis).

Management of patients at risk for thromboembolism and bleeding issues, particularly within the context of elective, urgent, or emergent orthopedic surgeries, is an evolving area. Understanding the pharmacokinetics, conventional laboratory tests, dosing, and reversal methods for NOACs is important, especially because clinical data are limited and the treatment itself can cause clinically significant harm.

In this article, we review the medical literature on these medications, their mechanism of action, and their reversal agents, and outline a practical approach for managing patients during the perioperative period.

Dabigatran

In October 2010, dabigatran became the first NOAC approved by the US Food and Drug Administration (FDA) for the prevention of arterial thromboembolic events in patients with nonvalvular AF, on the basis of the results of the RELY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial. Dabigatran is an oral factor IIA (thrombin) inhibitor. From time of ingestion, dabigatran takes 1.25 to 3 hours to reach peak plasma concentration. It has a half-life of 12 to 14 hours, is excreted predominantly by the kidneys (80%), and is renally dosed. The usual dose is 150 mg 2 times daily if creatinine clearance (CrCl) is >30 mL/minute, or 75 mg 2 times daily if CrCl is 15 to 30 mL/minute.³ Dabigatran is not recommended for patients with CrCl <15 mL/minute.

Dabigatran affects prothrombin time (PT), activated partial thromboplastin time (aPTT), ecarin clotting time, and thrombin time, with the latter 2 providing the most accurate means of monitoring appropriate drug levels.^3,4 Of the tests commonly used to assess coagulation hemostasis in hospitals, normalization of thrombin time and aPTT provide the most accurate results (Table 1). The pharmacokinetics of dabigatran mandate consideration of dose, time of ingestion relative to time of blood sampling, and renal function in the assessment of coagulation hemostasis.

For elective surgeries, the periprocedure recommendation for patients being treated with dabigatran is to discontinue the medication 3 to 4 days before an operation if CrCl is ≥50 mL/minute, or 4 to 5 days beforehand if CrCl is <50 mL/minute.³ There is no antidote for dabigatran. In an in vitro model, activated charcoal reduced 99.9% of dabigatran absorption after recent ingestion.³ According to case reports, acute hemodialysis successfully removed 60% of the medication after 6 hours.⁵ In patients with end-stage renal disease, hemodialysis removed up to 68% of active dabigatran after 4 hours.³

Pernod and colleagues6 proposed that urgent surgeries can proceed if the concentration of dabigatran is ≤30 ng/mL—equivalent to normal aPTT. Their dictum was extrapolated from the data of patients who underwent elective surgeries while being treated with dabigatran, as recorded during the RELY trial. According to Pernod and colleagues,⁶ if aPTT is increased (probable drug level, ≥30 ng/mL), surgery should be postponed for up to 12 hours, with aPTT checked again and the process repeated if the concentration of dabigatran is still elevated and surgery can continue to be delayed. In patients who require urgent surgical interventions, we previously utilized nanofiltered activated prothrombin complex concentrate (aPCC; Feiba NF) 30 to 50 IU/kg over prothrombin complex concentrate (PCC; Kcentra or Bebulin) 25 to 50 IU/kg, as supported by in vitro and animal model studies and anecdotal case reports. However, neither aPCC nor PCC fully corrects the abnormalities evident on hemostasis tests.3,6 In October 2015, the FDA approved Idarucizumab (Praxbind), an injectable monoclonal antibody fragment that binds to dabigatran, as a reversing agent for use in urgent/emergent settings. Recommendation is to administer two 50-ml bolus infusions, each containing 2.5 g of idarucizumab, no more than 15 minutes apart.⁷ Additionally, hemodialysis could be discussed before surgery, with the understanding that it will take a long time to reach the threshold of 30 ng/mL in these patients (Table 2).

Rivaroxaban

Rivaroxaban is an oral direct factor Xa inhibitor that was initially approved in November 2011 for the prevention of stroke and systemic embolism in patients with nonvalvular AF. Since then, clinical use of rivaroxaban has been expanded to include prevention of VTE after elective hip or knee arthroplasty as well as treatment of DVT and prevention of recurrent VTE after acute DVT. In the phase 3 ROCKET AF (Rivaroxaban Once-Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) study, rivaroxaban 20 mg daily (CrCl, ≥50 mL/min) and rivaroxaban 15 mg daily (CrCl, 15-49 mL/min) were equally effective as warfarin. Compared with warfarin, rivaroxaban had a similar safety rate for bleeding and adverse events but fewer intracranial hemorrhage and fatal bleeding events.⁸ On the basis of the outcomes of the RECORD (Regulation of Coagulation in Orthopedic Surgery to Prevent Deep Venous Thrombosis and Pulmonary Embolism) studies comparing rivaroxaban and enoxaparin sodium, rivaroxaban 10 mg daily was approved for the prevention of VTE and pulmonary embolism after elective hip or knee arthroplasty.⁸

The half-life of rivaroxaban is 5 to 9 hours in the young and 11 to 13 hours in the elderly.⁸ As rivaroxaban takes 2 to 4 hours after ingestion to reach peak plasma concentration, it is important to know the timing and the dose taken. Because of the short half-life and rapid onset of action of this medication, bridging with another anticoagulant is not required when rivaroxaban is discontinued before surgery or initiated after surgery.⁸ The recommendation is to withhold rivaroxaban for 24 to 48 hours before surgery and then to administer the first postoperative dose 6 to 10 hours after surgery, or when hemostasis is achieved (Table 1).

PT is recommended for rivaroxaban detection. Conventional assays are not sensitive at low concentrations, and degree of prolongation does not reliably predict amount of medication present.^3,9 However, normal PT corresponds to a drug concentration of about 30 ng/mL and is considered safe for patients undergoing surgical intervention without increased risk for bleeding.⁶ This recommendation was extrapolated from data in the ROCKET AF study of patients who underwent elective surgeries while on rivaroxaban.⁶ Commercially available chromogenic anti–factor Xa assays, used with a rivaroxaban calibration curve, are sensitive and specific for rivaroxaban plasma concentrations.^3,8 However, these assays are not widely available.

If a bleeding complication occurs in a patient who is being treated with rivaroxaban, the next rivaroxaban dose should be delayed, or treatment should be discontinued, as appropriate.⁸ Urgency of surgery should be weighed against risk for bleeding complications on a case-by-case basis. This decision is deferred to the clinical judgment of the surgeon. In the case of a patient with severe, life-threatening bleeding or a patient who requires emergent surgery, PCC 25-50 IU/kg is the recommended reversal agent.⁹ Recombinant factor VIIa and aPCC have been used in experimental settings, but there is concern about the greater prothrombotic potential of these agents compared with PCC⁸ (Table 2).

Apixaban

Apixaban is the second factor Xa inhibitor introduced in the United States and the first to show—in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) study—efficacy superior to that of warfarin for the prevention of stroke and systemic embolism, all-cause mortality, and major bleeding. Furthermore, in the AVERROES (Apixaban Versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment) study, apixaban used in AF patients who were deemed not suitable for warfarin proved to be more effective than aspirin for stroke prevention, and had a similar rate of major bleeding.¹⁰ Apixaban is administered in a 5-mg dose 2 times daily. It has a half-life of 10 to 14 hours, is highly protein-bound, and has predominantly fecal excretion (27% is renal). Apixaban can prolong PT, but the correlation is nonlinear. Barrett and colleagues¹¹ found that chromogenic anti–factor Xa assays provided the most accurate readings of apixaban plasma concentrations. Normal anti–factor Xa activity in patients being treated with apixaban suggests low drug levels and an intact hemostatic function, which are indicators of low bleeding risk with surgical intervention³ (Table 1).

Similar to other NOACs, apixaban has no antidote. In vitro testing showed that PCC improved thrombin generation when added to the blood of healthy donors who had received apixaban. Despite the lack of clinical experience, use of PCC 50 IU/kg may be reasonable for apixaban patients with severe or life-threatening bleeding³ (Table 2). Unlike dabigatran, apixaban cannot be eliminated with dialysis because of its high degree of protein binding. In nonemergent circumstances, delaying surgery 24 to 48 hours is considered effective in reducing the concentration of apixaban to a range that does not cause additional risk for bleeding.

Conclusion

Compared with warfarin, the NOACs dabigatran, rivaroxaban, and apixaban are efficacious and safe. Because of their steady pharmacokinetics, they do not require regular coagulation testing, as is the case with warfarin. These NOACs have been approved for the prevention of stroke and thromboembolic events in patients with nonvalvular AF; rivaroxaban has also been approved for VTE prevention after total hip or knee arthroplasty, for DVT treatment, and for prevention of recurrent VTE after acute DVT. Other options for VTE prophylaxis after hip and knee surgery are addressed in the guidelines issued by the American Academy of Orthopaedic Surgeons in 2011.¹² As the incidence of chronic anticoagulation continues to increase among patients undergoing TJA, orthopedic surgeons need to be aware of the mechanism of action of these NOACs, as well as their pharmacokinetics and available reversal agents. Aggarwal and colleagues1 found that AF patients undergoing TJA had longer hospital stays, increased transfusion requirements, and increased risk for periprosthetic joint infection and unplanned hospital readmission.

The anticoagulation tests recommended for evaluation of hemostasis and drug reversal are normalization of aPTT for dabigatran; PT for rivaroxaban; and chromogenic anti–factor Xa activity for apixaban³ (Table 2). Although several research projects are being planned to develop an antidote for these medications, no antidote has been approved for human trials. The coagulation agents currently being used for reversal of NOACs are nonactivated PCC (Kcentra, Bebulin) and aPCC. Kcentra is a 4-factor PCC (II, VII, IX, X), and Bebulin is a 3-factor PCC (II, IX, X). Most authors recommend using 4-factor PCC 25 to 50 IU/kg. In vivo studies and animal studies have shown that nanofiltered aPCC (Feiba NF) at doses of 30 to 50 IU/kg can to some extent reverse anticoagulation in patients receiving NOACs. The current, limited data support use of reversal agent PCC for rivaroxaban and apixaban (no human studies for apixaban) and use of aPCC for dabigatran.^3,6,8 Activated charcoal can be used for patients who have taken dabigatran <6 hours before presentation.³ Hemodialysis is another option for dabigatran removal. Hemodialysis, however, takes 4 to 6 hours or longer to remove about 60% of the medication (Table 2).^3,5

In major orthopedic surgeries, such as TJA, bleeding is a critical concern. Using reversal agents to overcome the anticoagulation effect adds to the potential concern for thromboembolism secondary to these agents. Therefore, in cases in which surgery cannot be delayed any longer, the decision to use reversal agents should be made on a case-by-case basis. For most patients on rivaroxaban or apixaban, it is sufficient to delay for 24 to 48 hours before proceeding safely with surgery; for dabigatran, a delay of 3 to 4 days is recommended. Delay before surgery may need to be extended for the elderly and for patients with renal failure. The pharmacokinetics of these medications is summarized in Table 1.

There are no guidelines for perioperative management of patients undergoing elective, urgent, or emergent surgeries while on NOACs. As discussed, Pernod and colleagues6 proposed better perioperative management of major bleeding risks in patients receiving rivaroxaban or dabigatran. Adapting their approach, and using the data available from the medical literature, we propose a perioperative algorithm that can guide practicing orthopedic surgeons performing urgent and emergent surgeries (Figure).

The population of patients receiving chronic anticoagulation therapy is growing, and anticoagulant and antiplatelet options are increasing in the United States and around the world. We propose a team approach for patient care, with orthopedic surgeon and cardiologist or vascular medicine specialist collaborating to ensure the safety and effectiveness of this treatment.

MACRA will not be as hard on small and solo practices as it first appeared when draft implementing regulations were published, according to Andy Slavitt, administrator of the Centers for Medicare & Medicaid Services.

Mr. Slavitt testified May 11 before the House Ways & Means Health Subcommittee to address legislators’ concerns about how the government intends to implement the Medicare Access and CHIP Reauthorization Act of 2015.

Rep. Sam Johnson (R-Tex.) expressed concern that the draft regulations published April 27 project “the greatest negative impact on payments to practices with nine or fewer doctors and the least harm to large systems with 100 or more docs.”

The calculations in the draft regulation were based on data from 2014, a year in which few small and solo practices reported quality data.

“In 2015 and subsequent years, the reporting went up,” Mr. Slavitt testified. “So at best, this table would be very, very conservative. ... Reporting is going to be far easier going forward.”

Mr. Slavitt said that the CMS will do all it can to help ensure that small and solo practices have every opportunity to participate in the both the Merit-Based Incentive Payment System (MIPS) and in advanced alternative payment models.

“The question of making sure that small groups and solo practitioners can be successful is of utmost importance. Our data show that physicians who are in small and solo practices ... do just as well as physicians that are in practices that are larger than that,” he said, adding that technical assistance specific to solo and small practices is being developed to help them transition to these value-based payment models.

Other federal officials have been spreading the same message to physicians. Speaking May 7 at the annual meeting of the American College of Physicians, Dr. Thomas A. Mason, chief medical officer in the Office of the National Coordinator for Health Information Technology, pointed out that the MACRA legislation put aside $20 million a year for 5 years beginning in 2016 to help solo and small practices transition to MIPS and APMs.

“It is specifically to help with the shift and transforming practices to measuring quality and improving quality performance,” he said in an interview. “The MACRA statute specifically calls out what the dollars need to be used for and the two points are for assisting MIPS-eligible professionals and improving their MIPS composite score as well as the transition to advanced alternative payment models.”

The U.S. Department of Health & Human Services already has begun soliciting contractors to support small and solo practices, he added.

“Direct technical assistance through this program will target eligible clinicians in individual or small group practices of 15 or fewer, focusing on those practicing in historically under resourced areas,” according to a request for proposals. “Technical assistance is defined as provider outreach and education, practice readiness, practice facilitation, health information technology (HIT) optimization, practice workflow redesign, change management, strategic planning, assisting clinicians in fully transitioning to Alternative Payment Models, and enabling partnerships.”

The federal health IT office plans to provide more information on the availability of transition assistance soon, Dr. Mason said.

[email protected]

MACRA will not be as hard on small and solo practices as it first appeared when draft implementing regulations were published, according to Andy Slavitt, administrator of the Centers for Medicare & Medicaid Services.

Mr. Slavitt testified May 11 before the House Ways & Means Health Subcommittee to address legislators’ concerns about how the government intends to implement the Medicare Access and CHIP Reauthorization Act of 2015.

Rep. Sam Johnson (R-Tex.) expressed concern that the draft regulations published April 27 project “the greatest negative impact on payments to practices with nine or fewer doctors and the least harm to large systems with 100 or more docs.”

The calculations in the draft regulation were based on data from 2014, a year in which few small and solo practices reported quality data.

“In 2015 and subsequent years, the reporting went up,” Mr. Slavitt testified. “So at best, this table would be very, very conservative. ... Reporting is going to be far easier going forward.”

Mr. Slavitt said that the CMS will do all it can to help ensure that small and solo practices have every opportunity to participate in the both the Merit-Based Incentive Payment System (MIPS) and in advanced alternative payment models.

“The question of making sure that small groups and solo practitioners can be successful is of utmost importance. Our data show that physicians who are in small and solo practices ... do just as well as physicians that are in practices that are larger than that,” he said, adding that technical assistance specific to solo and small practices is being developed to help them transition to these value-based payment models.

Other federal officials have been spreading the same message to physicians. Speaking May 7 at the annual meeting of the American College of Physicians, Dr. Thomas A. Mason, chief medical officer in the Office of the National Coordinator for Health Information Technology, pointed out that the MACRA legislation put aside $20 million a year for 5 years beginning in 2016 to help solo and small practices transition to MIPS and APMs.

“It is specifically to help with the shift and transforming practices to measuring quality and improving quality performance,” he said in an interview. “The MACRA statute specifically calls out what the dollars need to be used for and the two points are for assisting MIPS-eligible professionals and improving their MIPS composite score as well as the transition to advanced alternative payment models.”

The U.S. Department of Health & Human Services already has begun soliciting contractors to support small and solo practices, he added.

“Direct technical assistance through this program will target eligible clinicians in individual or small group practices of 15 or fewer, focusing on those practicing in historically under resourced areas,” according to a request for proposals. “Technical assistance is defined as provider outreach and education, practice readiness, practice facilitation, health information technology (HIT) optimization, practice workflow redesign, change management, strategic planning, assisting clinicians in fully transitioning to Alternative Payment Models, and enabling partnerships.”

The federal health IT office plans to provide more information on the availability of transition assistance soon, Dr. Mason said.

[email protected]

MACRA will not be as hard on small and solo practices as it first appeared when draft implementing regulations were published, according to Andy Slavitt, administrator of the Centers for Medicare & Medicaid Services.

Mr. Slavitt testified May 11 before the House Ways & Means Health Subcommittee to address legislators’ concerns about how the government intends to implement the Medicare Access and CHIP Reauthorization Act of 2015.

Rep. Sam Johnson (R-Tex.) expressed concern that the draft regulations published April 27 project “the greatest negative impact on payments to practices with nine or fewer doctors and the least harm to large systems with 100 or more docs.”

The calculations in the draft regulation were based on data from 2014, a year in which few small and solo practices reported quality data.

“In 2015 and subsequent years, the reporting went up,” Mr. Slavitt testified. “So at best, this table would be very, very conservative. ... Reporting is going to be far easier going forward.”

Mr. Slavitt said that the CMS will do all it can to help ensure that small and solo practices have every opportunity to participate in the both the Merit-Based Incentive Payment System (MIPS) and in advanced alternative payment models.

“The question of making sure that small groups and solo practitioners can be successful is of utmost importance. Our data show that physicians who are in small and solo practices ... do just as well as physicians that are in practices that are larger than that,” he said, adding that technical assistance specific to solo and small practices is being developed to help them transition to these value-based payment models.

Other federal officials have been spreading the same message to physicians. Speaking May 7 at the annual meeting of the American College of Physicians, Dr. Thomas A. Mason, chief medical officer in the Office of the National Coordinator for Health Information Technology, pointed out that the MACRA legislation put aside $20 million a year for 5 years beginning in 2016 to help solo and small practices transition to MIPS and APMs.

“It is specifically to help with the shift and transforming practices to measuring quality and improving quality performance,” he said in an interview. “The MACRA statute specifically calls out what the dollars need to be used for and the two points are for assisting MIPS-eligible professionals and improving their MIPS composite score as well as the transition to advanced alternative payment models.”

The U.S. Department of Health & Human Services already has begun soliciting contractors to support small and solo practices, he added.

“Direct technical assistance through this program will target eligible clinicians in individual or small group practices of 15 or fewer, focusing on those practicing in historically under resourced areas,” according to a request for proposals. “Technical assistance is defined as provider outreach and education, practice readiness, practice facilitation, health information technology (HIT) optimization, practice workflow redesign, change management, strategic planning, assisting clinicians in fully transitioning to Alternative Payment Models, and enabling partnerships.”

The federal health IT office plans to provide more information on the availability of transition assistance soon, Dr. Mason said.

[email protected]

Brain cancer rates have declined slightly in recent years, according to the Annual Report to the Nation on the Status of Cancer, 1975-2012, which tracks trends in cancer incidence and deaths in the U.S.

Between 2003 and 2012, brain cancer was 1 of 7 common cancers for which incidence rates dropped among men. Death rates remained stable among men during that time for melanoma and cancers of the bladder, brain, oral cavity, and pharynx. Between 2003 and 2012, brain cancer ranked 11th of the top 17 cancers for whites, 15th for blacks, 13th for Asian/Pacific Islanders (API), 14th for American Indian/Alaska Natives (AI/AN), and 13th for Hispanics.

Related: Major Cancer Death Rates Are Down

When data from 1975 through 2012 were factored in, the long-term trend was a general decline in cancer deaths for adults. Overall, cancer deaths for both sexes decreased by 1.5% per year between 2003 and 2012. For men in all ethnic and racial groups, rates of brain cancer also trended downward. The annual percent change was 4.4% between 1975 and 1977; -0.4% between 1977 and 1982, 1.3% between 1982 and 1991, -1.0% between 1991 and 2007, and 0.7% between 2007 and 2012.

Among women, death rates declined slightly overall but remained stable for brain cancer. Between 2003 and 2012, brain cancer ranked 9th among the top 17 cancers for whites, 15th for blacks, 12th for API, 14th for AI/AN, and 12th for Hispanics.

Related: Predicting Tongue Cancer Recurrence

The annual updates are the joint production of The American Cancer Society, the CDC, National Cancer Institute, and the North American Association of Central Cancer Registries. This is the 18th year the report has been published.

Source:
Ryerson AB, Eheman CR, Altekruse SF, et al. Cancer. 2016;122(9):1312-137.
doi: 10.1002/cncr.29936.

Brain cancer rates have declined slightly in recent years, according to the Annual Report to the Nation on the Status of Cancer, 1975-2012, which tracks trends in cancer incidence and deaths in the U.S.

Between 2003 and 2012, brain cancer was 1 of 7 common cancers for which incidence rates dropped among men. Death rates remained stable among men during that time for melanoma and cancers of the bladder, brain, oral cavity, and pharynx. Between 2003 and 2012, brain cancer ranked 11th of the top 17 cancers for whites, 15th for blacks, 13th for Asian/Pacific Islanders (API), 14th for American Indian/Alaska Natives (AI/AN), and 13th for Hispanics.

Related: Major Cancer Death Rates Are Down

When data from 1975 through 2012 were factored in, the long-term trend was a general decline in cancer deaths for adults. Overall, cancer deaths for both sexes decreased by 1.5% per year between 2003 and 2012. For men in all ethnic and racial groups, rates of brain cancer also trended downward. The annual percent change was 4.4% between 1975 and 1977; -0.4% between 1977 and 1982, 1.3% between 1982 and 1991, -1.0% between 1991 and 2007, and 0.7% between 2007 and 2012.

Among women, death rates declined slightly overall but remained stable for brain cancer. Between 2003 and 2012, brain cancer ranked 9th among the top 17 cancers for whites, 15th for blacks, 12th for API, 14th for AI/AN, and 12th for Hispanics.

Related: Predicting Tongue Cancer Recurrence

The annual updates are the joint production of The American Cancer Society, the CDC, National Cancer Institute, and the North American Association of Central Cancer Registries. This is the 18th year the report has been published.

Source:
Ryerson AB, Eheman CR, Altekruse SF, et al. Cancer. 2016;122(9):1312-137.
doi: 10.1002/cncr.29936.

Brain cancer rates have declined slightly in recent years, according to the Annual Report to the Nation on the Status of Cancer, 1975-2012, which tracks trends in cancer incidence and deaths in the U.S.

Between 2003 and 2012, brain cancer was 1 of 7 common cancers for which incidence rates dropped among men. Death rates remained stable among men during that time for melanoma and cancers of the bladder, brain, oral cavity, and pharynx. Between 2003 and 2012, brain cancer ranked 11th of the top 17 cancers for whites, 15th for blacks, 13th for Asian/Pacific Islanders (API), 14th for American Indian/Alaska Natives (AI/AN), and 13th for Hispanics.

Related: Major Cancer Death Rates Are Down

When data from 1975 through 2012 were factored in, the long-term trend was a general decline in cancer deaths for adults. Overall, cancer deaths for both sexes decreased by 1.5% per year between 2003 and 2012. For men in all ethnic and racial groups, rates of brain cancer also trended downward. The annual percent change was 4.4% between 1975 and 1977; -0.4% between 1977 and 1982, 1.3% between 1982 and 1991, -1.0% between 1991 and 2007, and 0.7% between 2007 and 2012.

Among women, death rates declined slightly overall but remained stable for brain cancer. Between 2003 and 2012, brain cancer ranked 9th among the top 17 cancers for whites, 15th for blacks, 12th for API, 14th for AI/AN, and 12th for Hispanics.

Related: Predicting Tongue Cancer Recurrence

The annual updates are the joint production of The American Cancer Society, the CDC, National Cancer Institute, and the North American Association of Central Cancer Registries. This is the 18th year the report has been published.

Source:
Ryerson AB, Eheman CR, Altekruse SF, et al. Cancer. 2016;122(9):1312-137.
doi: 10.1002/cncr.29936.

In recent years federal laws have been enacted to help provide more treatment options and possibly lower costs to patients for therapeutic biological products. You have likely heard or read about “biosimilars” on the U.S. drug market. But are you ready to make informed treatment decisions and answer patients’ questions about these new drugs?

Biosimilars are not “generic biologics.” Although the shared goal of making biosimilars and generic drugs available is to provide more treatment options, there are important differences between the two approval pathways. For instance, unlike generic drugs, which are “bioequivalent” to their reference listed drug, biosimilar products can be either “biosimilar” to or “interchangeable” with their reference product. The differences may seem subtle based on the terminology, but the differences are important, and health care professionals who prescribe, dispense, or administer these products will need to understand them – as well as other aspects of these new therapies.

To help busy health care professionals better understand biosimilar and interchangeable products, the FDA has created a free 1.5-hour continuing education program titled, FDA Overview of Biosimilar Products. The course describes the important characteristics of biological products, particularly their complexity. For instance, a single molecule of a biological product, such as a monoclonal antibody, can easily be many hundreds of times larger and much more complex than that of a “small molecule” drug such as aspirin. Their increased complexity is one reason they are regulated differently than generics – and why, in the case of biosimilars, the law allows some differences from the reference product in clinically inactive components. The CE course discusses the “inherent variability” in the production of all biological products – both reference and biosimilar – and how the FDA accounts for these differences in assessing safety and efficacy of the products. The course also provides detailed definitions of important terms – such as “biosimilar” and “interchangeable” – and an overview of the standards the FDA has established for reviewing and approving biosimilar and interchangeable products. It also outlines the FDA review and approval standards for biosimilars and interchangeable products to help practitioners be assured that these products have been demonstrated to be safe and effective treatment options for their patients.

Some of our most important and expensive drugs are biological products used to treat patients who have serious medical conditions that are often life threatening and usually life altering. In April 2016, the Food and Drug Administration approved Inflectra (infliximab-dyyb) to help treat certain patients with certain gastrointestinal disorders, such as Crohn’s disease, and for other indications such as treatment of psoriasis and rheumatoid arthritis. The product is approved but not yet marketed in the United States. However, last year, Zarxio (filgrastim-sndz) became the first biosimilar actually available in the U.S. marketplace – approved to help boost white blood cell production for patients with severe neutropenia as well as for patients receiving various cancer therapies. These products are “biosimilar” to already-approved biological products called “reference products.” Inflectra is biosimilar to the reference product, Remicade (infliximab), and Zarxio is biosimilar to Neupogen (filgrastim).

Use of safe and effective biosimilar and interchangeable biological products can potentially make treatment more affordable for patients in need and improve public health. As patients begin to ask about the use of biosimilar and interchangeable products, the FDA hopes this course will help prepare health care practitioners to make informed decisions on behalf of their patients.

Dr. Christl is Associate Director for Therapeutic Biologics at the Office of New Drugs, Center for Drug Evaluation and Research, FDA.

In recent years federal laws have been enacted to help provide more treatment options and possibly lower costs to patients for therapeutic biological products. You have likely heard or read about “biosimilars” on the U.S. drug market. But are you ready to make informed treatment decisions and answer patients’ questions about these new drugs?

Biosimilars are not “generic biologics.” Although the shared goal of making biosimilars and generic drugs available is to provide more treatment options, there are important differences between the two approval pathways. For instance, unlike generic drugs, which are “bioequivalent” to their reference listed drug, biosimilar products can be either “biosimilar” to or “interchangeable” with their reference product. The differences may seem subtle based on the terminology, but the differences are important, and health care professionals who prescribe, dispense, or administer these products will need to understand them – as well as other aspects of these new therapies.

To help busy health care professionals better understand biosimilar and interchangeable products, the FDA has created a free 1.5-hour continuing education program titled, FDA Overview of Biosimilar Products. The course describes the important characteristics of biological products, particularly their complexity. For instance, a single molecule of a biological product, such as a monoclonal antibody, can easily be many hundreds of times larger and much more complex than that of a “small molecule” drug such as aspirin. Their increased complexity is one reason they are regulated differently than generics – and why, in the case of biosimilars, the law allows some differences from the reference product in clinically inactive components. The CE course discusses the “inherent variability” in the production of all biological products – both reference and biosimilar – and how the FDA accounts for these differences in assessing safety and efficacy of the products. The course also provides detailed definitions of important terms – such as “biosimilar” and “interchangeable” – and an overview of the standards the FDA has established for reviewing and approving biosimilar and interchangeable products. It also outlines the FDA review and approval standards for biosimilars and interchangeable products to help practitioners be assured that these products have been demonstrated to be safe and effective treatment options for their patients.

Some of our most important and expensive drugs are biological products used to treat patients who have serious medical conditions that are often life threatening and usually life altering. In April 2016, the Food and Drug Administration approved Inflectra (infliximab-dyyb) to help treat certain patients with certain gastrointestinal disorders, such as Crohn’s disease, and for other indications such as treatment of psoriasis and rheumatoid arthritis. The product is approved but not yet marketed in the United States. However, last year, Zarxio (filgrastim-sndz) became the first biosimilar actually available in the U.S. marketplace – approved to help boost white blood cell production for patients with severe neutropenia as well as for patients receiving various cancer therapies. These products are “biosimilar” to already-approved biological products called “reference products.” Inflectra is biosimilar to the reference product, Remicade (infliximab), and Zarxio is biosimilar to Neupogen (filgrastim).

Use of safe and effective biosimilar and interchangeable biological products can potentially make treatment more affordable for patients in need and improve public health. As patients begin to ask about the use of biosimilar and interchangeable products, the FDA hopes this course will help prepare health care practitioners to make informed decisions on behalf of their patients.

Dr. Christl is Associate Director for Therapeutic Biologics at the Office of New Drugs, Center for Drug Evaluation and Research, FDA.

In recent years federal laws have been enacted to help provide more treatment options and possibly lower costs to patients for therapeutic biological products. You have likely heard or read about “biosimilars” on the U.S. drug market. But are you ready to make informed treatment decisions and answer patients’ questions about these new drugs?

Biosimilars are not “generic biologics.” Although the shared goal of making biosimilars and generic drugs available is to provide more treatment options, there are important differences between the two approval pathways. For instance, unlike generic drugs, which are “bioequivalent” to their reference listed drug, biosimilar products can be either “biosimilar” to or “interchangeable” with their reference product. The differences may seem subtle based on the terminology, but the differences are important, and health care professionals who prescribe, dispense, or administer these products will need to understand them – as well as other aspects of these new therapies.

To help busy health care professionals better understand biosimilar and interchangeable products, the FDA has created a free 1.5-hour continuing education program titled, FDA Overview of Biosimilar Products. The course describes the important characteristics of biological products, particularly their complexity. For instance, a single molecule of a biological product, such as a monoclonal antibody, can easily be many hundreds of times larger and much more complex than that of a “small molecule” drug such as aspirin. Their increased complexity is one reason they are regulated differently than generics – and why, in the case of biosimilars, the law allows some differences from the reference product in clinically inactive components. The CE course discusses the “inherent variability” in the production of all biological products – both reference and biosimilar – and how the FDA accounts for these differences in assessing safety and efficacy of the products. The course also provides detailed definitions of important terms – such as “biosimilar” and “interchangeable” – and an overview of the standards the FDA has established for reviewing and approving biosimilar and interchangeable products. It also outlines the FDA review and approval standards for biosimilars and interchangeable products to help practitioners be assured that these products have been demonstrated to be safe and effective treatment options for their patients.

Some of our most important and expensive drugs are biological products used to treat patients who have serious medical conditions that are often life threatening and usually life altering. In April 2016, the Food and Drug Administration approved Inflectra (infliximab-dyyb) to help treat certain patients with certain gastrointestinal disorders, such as Crohn’s disease, and for other indications such as treatment of psoriasis and rheumatoid arthritis. The product is approved but not yet marketed in the United States. However, last year, Zarxio (filgrastim-sndz) became the first biosimilar actually available in the U.S. marketplace – approved to help boost white blood cell production for patients with severe neutropenia as well as for patients receiving various cancer therapies. These products are “biosimilar” to already-approved biological products called “reference products.” Inflectra is biosimilar to the reference product, Remicade (infliximab), and Zarxio is biosimilar to Neupogen (filgrastim).

Use of safe and effective biosimilar and interchangeable biological products can potentially make treatment more affordable for patients in need and improve public health. As patients begin to ask about the use of biosimilar and interchangeable products, the FDA hopes this course will help prepare health care practitioners to make informed decisions on behalf of their patients.

Dr. Christl is Associate Director for Therapeutic Biologics at the Office of New Drugs, Center for Drug Evaluation and Research, FDA.