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Make teen suicide screenings a part of everyday practice
CHICAGO – at the annual meeting of the American Academy of Pediatrics.
An estimated 2 million teenagers, aged 15-19 years, have attempted suicide within the past year, based on data from the Centers for Disease Control and Prevention. According to the CDC’s 1991-2015 High School Youth Risk Behavior Survey data, nearly a third of students (30%) have felt so sad or helpless nearly daily for at least 2 weeks that they stopped doing their normal activities, and 18% had seriously considered suicide within the past year. One in seven (15%) had made a plan for attempting suicide, 9% had attempted suicide at least once, and 3% attempted suicide that required medical treatment. About twice as many females as males had considered, planned, and/or attempted suicide.
“The offspring of suicide attempters have a sixfold higher risk of suicide than their peers whose parents have not attempted suicide,” Dr. Cody said. Other major risk factors include a history of being bullied, a history of abuse, and a history of substance abuse, particularly alcohol and opioids.
Once you identify a patient at risk for suicide, Dr. Cody advised that you should follow a suicide assessment management protocol, such as the one developed by Angela Stanley, PsyD, of the Medical College of Wisconsin and the Children’s Hospital of Wisconsin, both in Milwaukee. Doctors should identify the teen’s intensity of suicidal ideation, ask how far they are in their plans, ascertain their access to means, create a safety plan, refer the patient for mental health care, and follow up frequently.
Dr. Cody emphasized that “suicide contracts” and “safety plans” are different things. Suicide pacts are agreements not to hurt oneself, whereas safety plans include concrete, collaborative, proactive steps a person will take if experiencing suicidal thoughts.
“There is no evidence that contracts prevent suicide, but a lot of research shows that safety or crisis plans are much more effective at preventing a person from committing suicide,” Dr. Cody stated.
The first step of screening is asking a patient directly whether they have ever wished they were dead or had thoughts about killing themselves.
“Some pediatricians are afraid to ask the questions because they’re afraid they’re going to put the idea of suicide in the child’s head, but there is no evidence that screening puts kids at risk,” Dr. Cody said. The other reason you may feel uneasy asking about self-harm is not knowing what to do if a teen says that she is feeling suicidal. That’s where an assessment protocol helps.
If a patient has considered suicide more than a month prior, it shouldn’t be ignored, although the situation may require less urgency but further follow-up. For those with more recent suicidal ideation but without a plan or intent, Dr. Cody recommends following up within 2 weeks because the adolescent’s situation may change.
For those with suicidal ideation and a plan, you should ask three questions:
- What ways of killing yourself have you thought about?
- How likely is it you will follow through on your plan?
- When you think about killing yourself, what stops you?
These questions can help you determine risk acuity: The more specific, realistic, available, and lethal a plan is, the more acute the risk. You then should ask questions to try to determine how likely the teen is to follow through, such as asking about his future plans, his connectedness with others, and his religious beliefs.
Asking about a plan helps determine how much access the patient has to a lethal, realistic means. Firearms are responsible for 52% of teen suicides, followed by hanging/suffocation (25%) and poisoning (16%).
“This is why it’s a really important part of social history to screen for guns in the house,” Dr. Cody told attendees. “I know it’s been really controversial, but it’s something that’s really important, especially if you have an adolescent in the house that’s having suicidal ideation.”
Teens with suicidal ideation and a plan but no intent require a safety plan along with follow-up within 1 week. Those with a plan and intent, or those with no intent but an unwillingness agree to a safety plan, should be immediately hospitalized, Dr. Cody said.
These suicide screenings should occur at annual well-child visits, Dr. Cody said, but they also should be done at acute visits; basically, any time you see your preteen and adolescent patients. Ideally, these should take place during alone time, without any parents present.
You also should share resources with your patients, including the National Suicide Prevention Lifeline at 1-800-273-8255 and the Crisis TextLine at 741741.
Dr. Cody reported having no disclosures, and no external funding was used for the presentation.
CHICAGO – at the annual meeting of the American Academy of Pediatrics.
An estimated 2 million teenagers, aged 15-19 years, have attempted suicide within the past year, based on data from the Centers for Disease Control and Prevention. According to the CDC’s 1991-2015 High School Youth Risk Behavior Survey data, nearly a third of students (30%) have felt so sad or helpless nearly daily for at least 2 weeks that they stopped doing their normal activities, and 18% had seriously considered suicide within the past year. One in seven (15%) had made a plan for attempting suicide, 9% had attempted suicide at least once, and 3% attempted suicide that required medical treatment. About twice as many females as males had considered, planned, and/or attempted suicide.
“The offspring of suicide attempters have a sixfold higher risk of suicide than their peers whose parents have not attempted suicide,” Dr. Cody said. Other major risk factors include a history of being bullied, a history of abuse, and a history of substance abuse, particularly alcohol and opioids.
Once you identify a patient at risk for suicide, Dr. Cody advised that you should follow a suicide assessment management protocol, such as the one developed by Angela Stanley, PsyD, of the Medical College of Wisconsin and the Children’s Hospital of Wisconsin, both in Milwaukee. Doctors should identify the teen’s intensity of suicidal ideation, ask how far they are in their plans, ascertain their access to means, create a safety plan, refer the patient for mental health care, and follow up frequently.
Dr. Cody emphasized that “suicide contracts” and “safety plans” are different things. Suicide pacts are agreements not to hurt oneself, whereas safety plans include concrete, collaborative, proactive steps a person will take if experiencing suicidal thoughts.
“There is no evidence that contracts prevent suicide, but a lot of research shows that safety or crisis plans are much more effective at preventing a person from committing suicide,” Dr. Cody stated.
The first step of screening is asking a patient directly whether they have ever wished they were dead or had thoughts about killing themselves.
“Some pediatricians are afraid to ask the questions because they’re afraid they’re going to put the idea of suicide in the child’s head, but there is no evidence that screening puts kids at risk,” Dr. Cody said. The other reason you may feel uneasy asking about self-harm is not knowing what to do if a teen says that she is feeling suicidal. That’s where an assessment protocol helps.
If a patient has considered suicide more than a month prior, it shouldn’t be ignored, although the situation may require less urgency but further follow-up. For those with more recent suicidal ideation but without a plan or intent, Dr. Cody recommends following up within 2 weeks because the adolescent’s situation may change.
For those with suicidal ideation and a plan, you should ask three questions:
- What ways of killing yourself have you thought about?
- How likely is it you will follow through on your plan?
- When you think about killing yourself, what stops you?
These questions can help you determine risk acuity: The more specific, realistic, available, and lethal a plan is, the more acute the risk. You then should ask questions to try to determine how likely the teen is to follow through, such as asking about his future plans, his connectedness with others, and his religious beliefs.
Asking about a plan helps determine how much access the patient has to a lethal, realistic means. Firearms are responsible for 52% of teen suicides, followed by hanging/suffocation (25%) and poisoning (16%).
“This is why it’s a really important part of social history to screen for guns in the house,” Dr. Cody told attendees. “I know it’s been really controversial, but it’s something that’s really important, especially if you have an adolescent in the house that’s having suicidal ideation.”
Teens with suicidal ideation and a plan but no intent require a safety plan along with follow-up within 1 week. Those with a plan and intent, or those with no intent but an unwillingness agree to a safety plan, should be immediately hospitalized, Dr. Cody said.
These suicide screenings should occur at annual well-child visits, Dr. Cody said, but they also should be done at acute visits; basically, any time you see your preteen and adolescent patients. Ideally, these should take place during alone time, without any parents present.
You also should share resources with your patients, including the National Suicide Prevention Lifeline at 1-800-273-8255 and the Crisis TextLine at 741741.
Dr. Cody reported having no disclosures, and no external funding was used for the presentation.
CHICAGO – at the annual meeting of the American Academy of Pediatrics.
An estimated 2 million teenagers, aged 15-19 years, have attempted suicide within the past year, based on data from the Centers for Disease Control and Prevention. According to the CDC’s 1991-2015 High School Youth Risk Behavior Survey data, nearly a third of students (30%) have felt so sad or helpless nearly daily for at least 2 weeks that they stopped doing their normal activities, and 18% had seriously considered suicide within the past year. One in seven (15%) had made a plan for attempting suicide, 9% had attempted suicide at least once, and 3% attempted suicide that required medical treatment. About twice as many females as males had considered, planned, and/or attempted suicide.
“The offspring of suicide attempters have a sixfold higher risk of suicide than their peers whose parents have not attempted suicide,” Dr. Cody said. Other major risk factors include a history of being bullied, a history of abuse, and a history of substance abuse, particularly alcohol and opioids.
Once you identify a patient at risk for suicide, Dr. Cody advised that you should follow a suicide assessment management protocol, such as the one developed by Angela Stanley, PsyD, of the Medical College of Wisconsin and the Children’s Hospital of Wisconsin, both in Milwaukee. Doctors should identify the teen’s intensity of suicidal ideation, ask how far they are in their plans, ascertain their access to means, create a safety plan, refer the patient for mental health care, and follow up frequently.
Dr. Cody emphasized that “suicide contracts” and “safety plans” are different things. Suicide pacts are agreements not to hurt oneself, whereas safety plans include concrete, collaborative, proactive steps a person will take if experiencing suicidal thoughts.
“There is no evidence that contracts prevent suicide, but a lot of research shows that safety or crisis plans are much more effective at preventing a person from committing suicide,” Dr. Cody stated.
The first step of screening is asking a patient directly whether they have ever wished they were dead or had thoughts about killing themselves.
“Some pediatricians are afraid to ask the questions because they’re afraid they’re going to put the idea of suicide in the child’s head, but there is no evidence that screening puts kids at risk,” Dr. Cody said. The other reason you may feel uneasy asking about self-harm is not knowing what to do if a teen says that she is feeling suicidal. That’s where an assessment protocol helps.
If a patient has considered suicide more than a month prior, it shouldn’t be ignored, although the situation may require less urgency but further follow-up. For those with more recent suicidal ideation but without a plan or intent, Dr. Cody recommends following up within 2 weeks because the adolescent’s situation may change.
For those with suicidal ideation and a plan, you should ask three questions:
- What ways of killing yourself have you thought about?
- How likely is it you will follow through on your plan?
- When you think about killing yourself, what stops you?
These questions can help you determine risk acuity: The more specific, realistic, available, and lethal a plan is, the more acute the risk. You then should ask questions to try to determine how likely the teen is to follow through, such as asking about his future plans, his connectedness with others, and his religious beliefs.
Asking about a plan helps determine how much access the patient has to a lethal, realistic means. Firearms are responsible for 52% of teen suicides, followed by hanging/suffocation (25%) and poisoning (16%).
“This is why it’s a really important part of social history to screen for guns in the house,” Dr. Cody told attendees. “I know it’s been really controversial, but it’s something that’s really important, especially if you have an adolescent in the house that’s having suicidal ideation.”
Teens with suicidal ideation and a plan but no intent require a safety plan along with follow-up within 1 week. Those with a plan and intent, or those with no intent but an unwillingness agree to a safety plan, should be immediately hospitalized, Dr. Cody said.
These suicide screenings should occur at annual well-child visits, Dr. Cody said, but they also should be done at acute visits; basically, any time you see your preteen and adolescent patients. Ideally, these should take place during alone time, without any parents present.
You also should share resources with your patients, including the National Suicide Prevention Lifeline at 1-800-273-8255 and the Crisis TextLine at 741741.
Dr. Cody reported having no disclosures, and no external funding was used for the presentation.
EXPERT ANALYSIS FROM AAP 2017
Full-spectrum family practice can still include obstetrics
For some patients in rural or otherwise underserved settings, the nearest obstetrician may be counties away. Other patients, though, seek the continuity of care that can come when one doctor cares for the whole family through all phases of life.
And physicians who choose to incorporate obstetrics into their range of practice do so to serve their communities but also because of the profound satisfaction they find in providing families care of this scope.
The American Academy of Family Practice makes it clear that full-spectrum family medicine still includes obstetrics. “We continue to support the full scope of practice for family physicians and training that supports that scope,” said Clif Knight, MD, senior vice president of education at the American Academy of Family Practice. “We believe that all family physicians should have a solid foundation of education in obstetrics, knowing that many will choose not to perform deliveries once they finish residency,” said Dr. Knight.
For those who really want to make obstetrics a focus or who are interested in teaching, a year-long postresidency obstetrics fellowship might make sense. “We absolutely are supportive of those family medicine grads who want to do additional training. That makes great sense to us,” said Dr. Knight.
For some family physicians, keeping an obstetrics practice, with its high level of engagement and procedural expertise, may actually ensure against burnout. Family physicians may have chosen the specialty because of the high priority they place on a wide scope of care that still puts human relationships first – and obstetrics certainly checks off those boxes, he said.
“We work hard to support our members who want to continue practicing obstetrics,” said Dr. Knight, noting that there’s an annual obstetrics-focused CME conference. When he attended the conference a few years ago, Dr. Knight “was struck by how mission-driven those family practice physicians are who continue to do obstetrics as part of their scope of practice,” he said. “They treasure that opportunity.”
Rural areas are the practice setting for many of the 17% of family physicians who report that they practice obstetrics. The family practice residency at the University of Wisconsin–Madison’s School of Medicine and Public Health includes an option for a rural training track; strong obstetrics training is woven through the residency curriculum.
The Baraboo approach
Since its inception in 1996, the Baraboo (Wisc.) rural residency has had 29 graduates, enrolling up to two residents per year. Two-thirds of the graduates now practice obstetrics, 69% are in rural areas, and about half have stayed in Wisconsin, said Sharilyn Munneke, MD, assistant program director for the residency. Dr. Munneke also heads up the obstetrics and women’s health curriculum for the residency.*
Residents who choose the Baraboo rural site for their training will spend their first postgraduate year in Madison, the state capital. The first year features a busy obstetrics rotation at a large community hospital, giving all residents a solid labor and delivery foundation. Rural track trainees also spend a day a week at a continuity clinic in Baraboo, a community of about 12,000 that’s an hour north of Madison.
Beginning in the second year, residents move to Baraboo; there, under supervision, “they essentially start functioning as a family doctor,” said Dr. Munneke in an interview, adding that the residents also have inpatient obstetrics and intensive care unit training at Baraboo’s 100-bed St. Clare Hospital.
The clinic setting gives residents an introduction to the multigenerational care that’s the hallmark of rural family medicine, as each succeeding class of residents inherits the graduating class’ panels. Patients come from the town, from surrounding agricultural and recreational areas, and from the Ho-Chunk Native American tribe, many of whose members live in the area. Residents begin to build their obstetrics practice from the clinic, she said, managing prenatal care, labor, and delivery under the supervision of family practice physicians who do obstetrics.
There is no obstetrician at St. Clare Hospital, but the rural-track residents still have the opportunity to assist at cesarean deliveries. “Our surgeons do our C-sections,” said Dr. Munneke, so residents will scrub in to assist the general surgeon on call for cesarean deliveries.
Dr. Munneke said that there are plenty of opportunities during training to learn other gynecologic procedures as well. “I teach colposcopies; I teach endometrial biopsies. I wrote a grant so we could get the equipment to do informal ultrasounds in the clinic, to assess for twins or for fetal viability,” she said.
Family practice physicians and residents in Baraboo have a good working relationship with Madison maternal-fetal medicine specialists and the referral hospital, she said, so that, even for high-risk pregnancies, as much care as possible can be delivered close to home. This is important for families whose farming obligations and family situations might make a woman’s prolonged absence incredibly difficult, said Dr. Munneke. Though women are referred to Madison for deliveries before 36 weeks, residents still receive neonatal resuscitation training, so they become comfortable stabilizing fragile neonates until transport is arranged.
For Rachel Hartline, MD, the Baraboo training experience was just what she’d been looking for. After completing medical school in her native Virginia, she realized that the family physicians she’d rotated with had been “excellent role models;” at the same time, she said, “I realized that their [practice] scope was not the scope I wanted to have.”
During her time in Baraboo, Dr. Hartline, who finished her residency in 2015, appreciated the opportunity for the “additional layer” that cesarean section training added for her. Whenever possible, she scrubbed in on scheduled cesareans. “There was also a C-section pager that was passed among those who were learning cesareans,” for additional opportunities when crash cesareans occurred, she said.
“My goal was 50 cesareans” during training, said Dr. Hartline. “I was a little shy of that,” she said, so her new partners in Dodgeville, Wisc. agreed to continue to mentor her through her first few cesarean deliveries.
Now, she is in a practice that includes obstetricians, with whom she splits obstetrics 1:4. Dodgeville’s Upland Hills Hospital is a critical-access hospital where approximately 300 babies are delivered yearly. Dr. Hartline said she’s also often called on to do deliveries for other physicians at one of the three groups who practice at Upland Hills.
Having a collaborative relationship with the community’s obstetricians is a real plus, said Dr. Hartline, who performs cesarean sections and is comfortable with vacuum deliveries, but doesn’t do forceps deliveries. “If I have a patient that seems too high, I might call one of my partners,” she said.
Upland Hills, like St. Clare, does not have a neonatal intensive care unit, so deliveries before 36 weeks are referred elsewhere whenever possible.
Dr. Hartline said that she also enjoys the full spectrum of family practice in her clinic. The agricultural area where she’s situated is home to many farm families, who she says can be reluctant to seek care, so chronic disease management can be a challenge. She also sees a growing number of undocumented immigrants as that population grows in rural Wisconsin. “I see all ages; I don’t say ‘no’ to much,” she said.
“But obstetrics is a big part of the reason why I’m a family doctor. It’s so cool to be a part of bringing someone’s child into the world and to be able to be there for them,” she said.
Cradle to grave
Dr. Hartline’s rural training classmate Rebecca Pfaff, MD, now lives and works in Vernon County, Wisc. The clinic and the small community hospital that are her practice home are in the small town of LaFarge. A native of Washington State, Dr. Pfaff thought she’d end up there after her undergraduate years at Wellesley College and her time at Meharry Medical College, a historically black medical school with a social justice focus in Nashville, Tenn.
She realized that in the right practice setting, she could find the scope she was seeking. “I became a family medicine doctor to do obstetrics, and to do family medicine,” she said.
Dr. Pfaff chose the Baraboo rural training track, still with the intention of eventually returning to practice in her home town of Port Angeles, Wash. There, the family practice group had already hired two Baraboo graduates, so they knew the strength of the program and recommended it to Dr. Pfaff.
Seeing patients living with the challenges of rural poverty, she said, helped her learn to care for women with substance use disorder and to gain experience caring for infants with neonatal abstinence syndrome. “That is the perfect setting for where family medicine thrives,” said Dr. Pfaff. Having established relationships with the mothers, she felt able to treat the mother-infant dyad as a unit, without judgment, and with natural opportunities for frequent follow-up.
Dr. Pfaff had a busy obstetrics practice in Baraboo and had the opportunity to perform cesarean sections. To feed her interest in low-intervention obstetrics, though, she sought and was able to secure a rotation in LaFarge, her eventual practice home.
Knowing she would return to LaFarge, Dr. Pfaff went on to complete a 1-year obstetrics fellowship at Swedish Hospital in Seattle. The obstetricians and family physicians there cared for high-risk patients from as far away as Alaska; her fellowship training, she said, was in many ways “the polar opposite” of the low-intervention, community-based work she’d done in Baraboo.
Still, she said, the fellowship gave her procedural expertise and boosted her confidence that she could handle many high-risk situations. She appreciated the perspective of some of her obstetrician instructors, who themselves had been solo practitioners in rural areas.
Her practice now, she says, is everything she’d hoped it would be. She sees patients in the clinic in a cradle-to-grave practice that includes many members of Vernon County, Wisconsin’s Amish community. Dr. Pfaff and her colleagues at the small clinic in LaFarge embrace the special challenges and rewards of obstetric care of a population that has traditionally had their babies at home.
The Amish community
Using low-intervention techniques is a priority, even when many Amish women have grand multiparity or present with other risk factors. “It’s not uncommon for us to see women on their twelfth or thirteenth pregnancy,” she said. Gestation dating is usually no more than a best guess, since women become pregnant while still amenorrheic from breastfeeding their last child.
Because the area’s Amish population has grown from a small group of founders who came to the hills of Vernon County in the late 1700s, there is an elevated rate of genetic disorders in the population, including metabolic disorders and congenital heart disease. Most Amish women return home within a few hours of delivery, and use no analgesia, even for breech and twin vaginal deliveries.
Though she’s comfortable with low-intervention care, Dr. Pfaff also performs cesarean sections at the community hospital when it’s indicated, sharing call duties with the community’s general surgeons. There’s no obstetrician in Vernon County.
The hospital is not equipped to care for preterm infants, so deliveries earlier than 36 weeks’ are referred, as are patients with abnormal placentation or fetal anomalies detected on ultrasound.
She loves the continuity that her practice now lets her have, said Dr. Pfaff. “When you’re seeing a woman in family medicine, instead of seeing her at 6 weeks, setting her up with contraception, and then seeing her again in a year, you’re seeing her every 2 weeks with that baby of hers,” she said. The care of mother and infant is so intertwined that sometimes it gives Dr. Pfaff pause, as when she tries to decide in whose chart she should be documenting. “They’re a unit at this time of their lives.”
When asked if she plans to stay put, Dr. Pfaff doesn’t hesitate. “Oh yes,” she said. “I’m so lucky.”
Dr. Hartline agreed. When asked what advice she’d give a trainee considering a rural, full-spectrum career path, she said, “This is a good life. Come and join us!”
Dr. Knight is an employee of AAFP. None of the physicians interviewed had financial conflicts of interest.
Correction, 9/22/17: An earlier version of this article misstated Dr. Munneke's title.
This article was updated 9/25/17.
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On Twitter @karioakes
For some patients in rural or otherwise underserved settings, the nearest obstetrician may be counties away. Other patients, though, seek the continuity of care that can come when one doctor cares for the whole family through all phases of life.
And physicians who choose to incorporate obstetrics into their range of practice do so to serve their communities but also because of the profound satisfaction they find in providing families care of this scope.
The American Academy of Family Practice makes it clear that full-spectrum family medicine still includes obstetrics. “We continue to support the full scope of practice for family physicians and training that supports that scope,” said Clif Knight, MD, senior vice president of education at the American Academy of Family Practice. “We believe that all family physicians should have a solid foundation of education in obstetrics, knowing that many will choose not to perform deliveries once they finish residency,” said Dr. Knight.
For those who really want to make obstetrics a focus or who are interested in teaching, a year-long postresidency obstetrics fellowship might make sense. “We absolutely are supportive of those family medicine grads who want to do additional training. That makes great sense to us,” said Dr. Knight.
For some family physicians, keeping an obstetrics practice, with its high level of engagement and procedural expertise, may actually ensure against burnout. Family physicians may have chosen the specialty because of the high priority they place on a wide scope of care that still puts human relationships first – and obstetrics certainly checks off those boxes, he said.
“We work hard to support our members who want to continue practicing obstetrics,” said Dr. Knight, noting that there’s an annual obstetrics-focused CME conference. When he attended the conference a few years ago, Dr. Knight “was struck by how mission-driven those family practice physicians are who continue to do obstetrics as part of their scope of practice,” he said. “They treasure that opportunity.”
Rural areas are the practice setting for many of the 17% of family physicians who report that they practice obstetrics. The family practice residency at the University of Wisconsin–Madison’s School of Medicine and Public Health includes an option for a rural training track; strong obstetrics training is woven through the residency curriculum.
The Baraboo approach
Since its inception in 1996, the Baraboo (Wisc.) rural residency has had 29 graduates, enrolling up to two residents per year. Two-thirds of the graduates now practice obstetrics, 69% are in rural areas, and about half have stayed in Wisconsin, said Sharilyn Munneke, MD, assistant program director for the residency. Dr. Munneke also heads up the obstetrics and women’s health curriculum for the residency.*
Residents who choose the Baraboo rural site for their training will spend their first postgraduate year in Madison, the state capital. The first year features a busy obstetrics rotation at a large community hospital, giving all residents a solid labor and delivery foundation. Rural track trainees also spend a day a week at a continuity clinic in Baraboo, a community of about 12,000 that’s an hour north of Madison.
Beginning in the second year, residents move to Baraboo; there, under supervision, “they essentially start functioning as a family doctor,” said Dr. Munneke in an interview, adding that the residents also have inpatient obstetrics and intensive care unit training at Baraboo’s 100-bed St. Clare Hospital.
The clinic setting gives residents an introduction to the multigenerational care that’s the hallmark of rural family medicine, as each succeeding class of residents inherits the graduating class’ panels. Patients come from the town, from surrounding agricultural and recreational areas, and from the Ho-Chunk Native American tribe, many of whose members live in the area. Residents begin to build their obstetrics practice from the clinic, she said, managing prenatal care, labor, and delivery under the supervision of family practice physicians who do obstetrics.
There is no obstetrician at St. Clare Hospital, but the rural-track residents still have the opportunity to assist at cesarean deliveries. “Our surgeons do our C-sections,” said Dr. Munneke, so residents will scrub in to assist the general surgeon on call for cesarean deliveries.
Dr. Munneke said that there are plenty of opportunities during training to learn other gynecologic procedures as well. “I teach colposcopies; I teach endometrial biopsies. I wrote a grant so we could get the equipment to do informal ultrasounds in the clinic, to assess for twins or for fetal viability,” she said.
Family practice physicians and residents in Baraboo have a good working relationship with Madison maternal-fetal medicine specialists and the referral hospital, she said, so that, even for high-risk pregnancies, as much care as possible can be delivered close to home. This is important for families whose farming obligations and family situations might make a woman’s prolonged absence incredibly difficult, said Dr. Munneke. Though women are referred to Madison for deliveries before 36 weeks, residents still receive neonatal resuscitation training, so they become comfortable stabilizing fragile neonates until transport is arranged.
For Rachel Hartline, MD, the Baraboo training experience was just what she’d been looking for. After completing medical school in her native Virginia, she realized that the family physicians she’d rotated with had been “excellent role models;” at the same time, she said, “I realized that their [practice] scope was not the scope I wanted to have.”
During her time in Baraboo, Dr. Hartline, who finished her residency in 2015, appreciated the opportunity for the “additional layer” that cesarean section training added for her. Whenever possible, she scrubbed in on scheduled cesareans. “There was also a C-section pager that was passed among those who were learning cesareans,” for additional opportunities when crash cesareans occurred, she said.
“My goal was 50 cesareans” during training, said Dr. Hartline. “I was a little shy of that,” she said, so her new partners in Dodgeville, Wisc. agreed to continue to mentor her through her first few cesarean deliveries.
Now, she is in a practice that includes obstetricians, with whom she splits obstetrics 1:4. Dodgeville’s Upland Hills Hospital is a critical-access hospital where approximately 300 babies are delivered yearly. Dr. Hartline said she’s also often called on to do deliveries for other physicians at one of the three groups who practice at Upland Hills.
Having a collaborative relationship with the community’s obstetricians is a real plus, said Dr. Hartline, who performs cesarean sections and is comfortable with vacuum deliveries, but doesn’t do forceps deliveries. “If I have a patient that seems too high, I might call one of my partners,” she said.
Upland Hills, like St. Clare, does not have a neonatal intensive care unit, so deliveries before 36 weeks are referred elsewhere whenever possible.
Dr. Hartline said that she also enjoys the full spectrum of family practice in her clinic. The agricultural area where she’s situated is home to many farm families, who she says can be reluctant to seek care, so chronic disease management can be a challenge. She also sees a growing number of undocumented immigrants as that population grows in rural Wisconsin. “I see all ages; I don’t say ‘no’ to much,” she said.
“But obstetrics is a big part of the reason why I’m a family doctor. It’s so cool to be a part of bringing someone’s child into the world and to be able to be there for them,” she said.
Cradle to grave
Dr. Hartline’s rural training classmate Rebecca Pfaff, MD, now lives and works in Vernon County, Wisc. The clinic and the small community hospital that are her practice home are in the small town of LaFarge. A native of Washington State, Dr. Pfaff thought she’d end up there after her undergraduate years at Wellesley College and her time at Meharry Medical College, a historically black medical school with a social justice focus in Nashville, Tenn.
She realized that in the right practice setting, she could find the scope she was seeking. “I became a family medicine doctor to do obstetrics, and to do family medicine,” she said.
Dr. Pfaff chose the Baraboo rural training track, still with the intention of eventually returning to practice in her home town of Port Angeles, Wash. There, the family practice group had already hired two Baraboo graduates, so they knew the strength of the program and recommended it to Dr. Pfaff.
Seeing patients living with the challenges of rural poverty, she said, helped her learn to care for women with substance use disorder and to gain experience caring for infants with neonatal abstinence syndrome. “That is the perfect setting for where family medicine thrives,” said Dr. Pfaff. Having established relationships with the mothers, she felt able to treat the mother-infant dyad as a unit, without judgment, and with natural opportunities for frequent follow-up.
Dr. Pfaff had a busy obstetrics practice in Baraboo and had the opportunity to perform cesarean sections. To feed her interest in low-intervention obstetrics, though, she sought and was able to secure a rotation in LaFarge, her eventual practice home.
Knowing she would return to LaFarge, Dr. Pfaff went on to complete a 1-year obstetrics fellowship at Swedish Hospital in Seattle. The obstetricians and family physicians there cared for high-risk patients from as far away as Alaska; her fellowship training, she said, was in many ways “the polar opposite” of the low-intervention, community-based work she’d done in Baraboo.
Still, she said, the fellowship gave her procedural expertise and boosted her confidence that she could handle many high-risk situations. She appreciated the perspective of some of her obstetrician instructors, who themselves had been solo practitioners in rural areas.
Her practice now, she says, is everything she’d hoped it would be. She sees patients in the clinic in a cradle-to-grave practice that includes many members of Vernon County, Wisconsin’s Amish community. Dr. Pfaff and her colleagues at the small clinic in LaFarge embrace the special challenges and rewards of obstetric care of a population that has traditionally had their babies at home.
The Amish community
Using low-intervention techniques is a priority, even when many Amish women have grand multiparity or present with other risk factors. “It’s not uncommon for us to see women on their twelfth or thirteenth pregnancy,” she said. Gestation dating is usually no more than a best guess, since women become pregnant while still amenorrheic from breastfeeding their last child.
Because the area’s Amish population has grown from a small group of founders who came to the hills of Vernon County in the late 1700s, there is an elevated rate of genetic disorders in the population, including metabolic disorders and congenital heart disease. Most Amish women return home within a few hours of delivery, and use no analgesia, even for breech and twin vaginal deliveries.
Though she’s comfortable with low-intervention care, Dr. Pfaff also performs cesarean sections at the community hospital when it’s indicated, sharing call duties with the community’s general surgeons. There’s no obstetrician in Vernon County.
The hospital is not equipped to care for preterm infants, so deliveries earlier than 36 weeks’ are referred, as are patients with abnormal placentation or fetal anomalies detected on ultrasound.
She loves the continuity that her practice now lets her have, said Dr. Pfaff. “When you’re seeing a woman in family medicine, instead of seeing her at 6 weeks, setting her up with contraception, and then seeing her again in a year, you’re seeing her every 2 weeks with that baby of hers,” she said. The care of mother and infant is so intertwined that sometimes it gives Dr. Pfaff pause, as when she tries to decide in whose chart she should be documenting. “They’re a unit at this time of their lives.”
When asked if she plans to stay put, Dr. Pfaff doesn’t hesitate. “Oh yes,” she said. “I’m so lucky.”
Dr. Hartline agreed. When asked what advice she’d give a trainee considering a rural, full-spectrum career path, she said, “This is a good life. Come and join us!”
Dr. Knight is an employee of AAFP. None of the physicians interviewed had financial conflicts of interest.
Correction, 9/22/17: An earlier version of this article misstated Dr. Munneke's title.
This article was updated 9/25/17.
[email protected]
On Twitter @karioakes
For some patients in rural or otherwise underserved settings, the nearest obstetrician may be counties away. Other patients, though, seek the continuity of care that can come when one doctor cares for the whole family through all phases of life.
And physicians who choose to incorporate obstetrics into their range of practice do so to serve their communities but also because of the profound satisfaction they find in providing families care of this scope.
The American Academy of Family Practice makes it clear that full-spectrum family medicine still includes obstetrics. “We continue to support the full scope of practice for family physicians and training that supports that scope,” said Clif Knight, MD, senior vice president of education at the American Academy of Family Practice. “We believe that all family physicians should have a solid foundation of education in obstetrics, knowing that many will choose not to perform deliveries once they finish residency,” said Dr. Knight.
For those who really want to make obstetrics a focus or who are interested in teaching, a year-long postresidency obstetrics fellowship might make sense. “We absolutely are supportive of those family medicine grads who want to do additional training. That makes great sense to us,” said Dr. Knight.
For some family physicians, keeping an obstetrics practice, with its high level of engagement and procedural expertise, may actually ensure against burnout. Family physicians may have chosen the specialty because of the high priority they place on a wide scope of care that still puts human relationships first – and obstetrics certainly checks off those boxes, he said.
“We work hard to support our members who want to continue practicing obstetrics,” said Dr. Knight, noting that there’s an annual obstetrics-focused CME conference. When he attended the conference a few years ago, Dr. Knight “was struck by how mission-driven those family practice physicians are who continue to do obstetrics as part of their scope of practice,” he said. “They treasure that opportunity.”
Rural areas are the practice setting for many of the 17% of family physicians who report that they practice obstetrics. The family practice residency at the University of Wisconsin–Madison’s School of Medicine and Public Health includes an option for a rural training track; strong obstetrics training is woven through the residency curriculum.
The Baraboo approach
Since its inception in 1996, the Baraboo (Wisc.) rural residency has had 29 graduates, enrolling up to two residents per year. Two-thirds of the graduates now practice obstetrics, 69% are in rural areas, and about half have stayed in Wisconsin, said Sharilyn Munneke, MD, assistant program director for the residency. Dr. Munneke also heads up the obstetrics and women’s health curriculum for the residency.*
Residents who choose the Baraboo rural site for their training will spend their first postgraduate year in Madison, the state capital. The first year features a busy obstetrics rotation at a large community hospital, giving all residents a solid labor and delivery foundation. Rural track trainees also spend a day a week at a continuity clinic in Baraboo, a community of about 12,000 that’s an hour north of Madison.
Beginning in the second year, residents move to Baraboo; there, under supervision, “they essentially start functioning as a family doctor,” said Dr. Munneke in an interview, adding that the residents also have inpatient obstetrics and intensive care unit training at Baraboo’s 100-bed St. Clare Hospital.
The clinic setting gives residents an introduction to the multigenerational care that’s the hallmark of rural family medicine, as each succeeding class of residents inherits the graduating class’ panels. Patients come from the town, from surrounding agricultural and recreational areas, and from the Ho-Chunk Native American tribe, many of whose members live in the area. Residents begin to build their obstetrics practice from the clinic, she said, managing prenatal care, labor, and delivery under the supervision of family practice physicians who do obstetrics.
There is no obstetrician at St. Clare Hospital, but the rural-track residents still have the opportunity to assist at cesarean deliveries. “Our surgeons do our C-sections,” said Dr. Munneke, so residents will scrub in to assist the general surgeon on call for cesarean deliveries.
Dr. Munneke said that there are plenty of opportunities during training to learn other gynecologic procedures as well. “I teach colposcopies; I teach endometrial biopsies. I wrote a grant so we could get the equipment to do informal ultrasounds in the clinic, to assess for twins or for fetal viability,” she said.
Family practice physicians and residents in Baraboo have a good working relationship with Madison maternal-fetal medicine specialists and the referral hospital, she said, so that, even for high-risk pregnancies, as much care as possible can be delivered close to home. This is important for families whose farming obligations and family situations might make a woman’s prolonged absence incredibly difficult, said Dr. Munneke. Though women are referred to Madison for deliveries before 36 weeks, residents still receive neonatal resuscitation training, so they become comfortable stabilizing fragile neonates until transport is arranged.
For Rachel Hartline, MD, the Baraboo training experience was just what she’d been looking for. After completing medical school in her native Virginia, she realized that the family physicians she’d rotated with had been “excellent role models;” at the same time, she said, “I realized that their [practice] scope was not the scope I wanted to have.”
During her time in Baraboo, Dr. Hartline, who finished her residency in 2015, appreciated the opportunity for the “additional layer” that cesarean section training added for her. Whenever possible, she scrubbed in on scheduled cesareans. “There was also a C-section pager that was passed among those who were learning cesareans,” for additional opportunities when crash cesareans occurred, she said.
“My goal was 50 cesareans” during training, said Dr. Hartline. “I was a little shy of that,” she said, so her new partners in Dodgeville, Wisc. agreed to continue to mentor her through her first few cesarean deliveries.
Now, she is in a practice that includes obstetricians, with whom she splits obstetrics 1:4. Dodgeville’s Upland Hills Hospital is a critical-access hospital where approximately 300 babies are delivered yearly. Dr. Hartline said she’s also often called on to do deliveries for other physicians at one of the three groups who practice at Upland Hills.
Having a collaborative relationship with the community’s obstetricians is a real plus, said Dr. Hartline, who performs cesarean sections and is comfortable with vacuum deliveries, but doesn’t do forceps deliveries. “If I have a patient that seems too high, I might call one of my partners,” she said.
Upland Hills, like St. Clare, does not have a neonatal intensive care unit, so deliveries before 36 weeks are referred elsewhere whenever possible.
Dr. Hartline said that she also enjoys the full spectrum of family practice in her clinic. The agricultural area where she’s situated is home to many farm families, who she says can be reluctant to seek care, so chronic disease management can be a challenge. She also sees a growing number of undocumented immigrants as that population grows in rural Wisconsin. “I see all ages; I don’t say ‘no’ to much,” she said.
“But obstetrics is a big part of the reason why I’m a family doctor. It’s so cool to be a part of bringing someone’s child into the world and to be able to be there for them,” she said.
Cradle to grave
Dr. Hartline’s rural training classmate Rebecca Pfaff, MD, now lives and works in Vernon County, Wisc. The clinic and the small community hospital that are her practice home are in the small town of LaFarge. A native of Washington State, Dr. Pfaff thought she’d end up there after her undergraduate years at Wellesley College and her time at Meharry Medical College, a historically black medical school with a social justice focus in Nashville, Tenn.
She realized that in the right practice setting, she could find the scope she was seeking. “I became a family medicine doctor to do obstetrics, and to do family medicine,” she said.
Dr. Pfaff chose the Baraboo rural training track, still with the intention of eventually returning to practice in her home town of Port Angeles, Wash. There, the family practice group had already hired two Baraboo graduates, so they knew the strength of the program and recommended it to Dr. Pfaff.
Seeing patients living with the challenges of rural poverty, she said, helped her learn to care for women with substance use disorder and to gain experience caring for infants with neonatal abstinence syndrome. “That is the perfect setting for where family medicine thrives,” said Dr. Pfaff. Having established relationships with the mothers, she felt able to treat the mother-infant dyad as a unit, without judgment, and with natural opportunities for frequent follow-up.
Dr. Pfaff had a busy obstetrics practice in Baraboo and had the opportunity to perform cesarean sections. To feed her interest in low-intervention obstetrics, though, she sought and was able to secure a rotation in LaFarge, her eventual practice home.
Knowing she would return to LaFarge, Dr. Pfaff went on to complete a 1-year obstetrics fellowship at Swedish Hospital in Seattle. The obstetricians and family physicians there cared for high-risk patients from as far away as Alaska; her fellowship training, she said, was in many ways “the polar opposite” of the low-intervention, community-based work she’d done in Baraboo.
Still, she said, the fellowship gave her procedural expertise and boosted her confidence that she could handle many high-risk situations. She appreciated the perspective of some of her obstetrician instructors, who themselves had been solo practitioners in rural areas.
Her practice now, she says, is everything she’d hoped it would be. She sees patients in the clinic in a cradle-to-grave practice that includes many members of Vernon County, Wisconsin’s Amish community. Dr. Pfaff and her colleagues at the small clinic in LaFarge embrace the special challenges and rewards of obstetric care of a population that has traditionally had their babies at home.
The Amish community
Using low-intervention techniques is a priority, even when many Amish women have grand multiparity or present with other risk factors. “It’s not uncommon for us to see women on their twelfth or thirteenth pregnancy,” she said. Gestation dating is usually no more than a best guess, since women become pregnant while still amenorrheic from breastfeeding their last child.
Because the area’s Amish population has grown from a small group of founders who came to the hills of Vernon County in the late 1700s, there is an elevated rate of genetic disorders in the population, including metabolic disorders and congenital heart disease. Most Amish women return home within a few hours of delivery, and use no analgesia, even for breech and twin vaginal deliveries.
Though she’s comfortable with low-intervention care, Dr. Pfaff also performs cesarean sections at the community hospital when it’s indicated, sharing call duties with the community’s general surgeons. There’s no obstetrician in Vernon County.
The hospital is not equipped to care for preterm infants, so deliveries earlier than 36 weeks’ are referred, as are patients with abnormal placentation or fetal anomalies detected on ultrasound.
She loves the continuity that her practice now lets her have, said Dr. Pfaff. “When you’re seeing a woman in family medicine, instead of seeing her at 6 weeks, setting her up with contraception, and then seeing her again in a year, you’re seeing her every 2 weeks with that baby of hers,” she said. The care of mother and infant is so intertwined that sometimes it gives Dr. Pfaff pause, as when she tries to decide in whose chart she should be documenting. “They’re a unit at this time of their lives.”
When asked if she plans to stay put, Dr. Pfaff doesn’t hesitate. “Oh yes,” she said. “I’m so lucky.”
Dr. Hartline agreed. When asked what advice she’d give a trainee considering a rural, full-spectrum career path, she said, “This is a good life. Come and join us!”
Dr. Knight is an employee of AAFP. None of the physicians interviewed had financial conflicts of interest.
Correction, 9/22/17: An earlier version of this article misstated Dr. Munneke's title.
This article was updated 9/25/17.
[email protected]
On Twitter @karioakes
ACOG urges standardization of postpartum hemorrhage treatment
Ob.gyns. and hospitals should have an organized and systematic treatment plan for postpartum hemorrhage, according to an updated practice bulletin from the American College of Obstetricians and Gynecologists (ACOG).
ACOG is recommending that obstetric care facilities post guidelines regarding the diagnosis methods and management techniques of postpartum hemorrhage. If postpartum hemorrhage is suspected, a physical exam should be performed to quickly inspect the uterus, cervix, vulva, and perineum to identify the source of bleeding. Once the cause has been identified, a treatment plan specific to the etiology of the bleeding can be implemented (Obstet Gynecol. 2017;130:e168-86).
“Less invasive methods should always be used first,” Aaron Caughey, MD, PhD, one of the coauthors of the practice bulletin, said in a statement. “If those methods fail, then more aggressive interventions must be considered to preserve the life of the mother.”
The ACOG reVITALize program defines postpartum hemorrhage “as cumulative blood loss greater than or equal to 1,000 mL or blood loss accompanied by signs or symptoms of hypovolemia within 24 hours after the birth process,” which differs from more traditional definitions of postpartum hemorrhage that puts the blood loss at more than 500 mL after vaginal birth and more than 1,000 mL after cesarean delivery.
The unpredictable nature of postpartum hemorrhage and its potential for severe morbidity and mortality make identifying its risk factors a priority. Risk assessment tools have been shown to identify 60%-85% of patients who will experience a serious hemorrhagic event. Risk factors for postpartum hemorrhage can be made into a simple table that categorizes different factors into low, medium, or high risk categories and posted in obstetric care facilities.
“The important thing is for providers to be able to recognize the signs and symptoms of excessive blood loss earlier and to have the resources at hand for the prompt escalation to more aggressive interventions if other therapies fail,” said Dr. Caughey, professor and chair of obstetrics and gynecology at Oregon Health and Science University, Portland.
Prevention is one of the key strategies outlined for combating postpartum hemorrhage. Many clinicians and organizations advise active management of the third stage of labor to decrease the likelihood of women experiencing postpartum hemorrhage. This can be done by administering oxytocin, massaging the uterus, and traction of the umbilical cord. Oxytocin can be administered both intravenously and intramuscularly and presents the lowest risk of adverse affects.
“By implementing standard protocols, we can improve outcomes,” Dr. Caughey said. “And this is even more critical for rural hospitals that often do not have the ability to treat a woman who may need a massive blood transfusion. They need to have a response plan in place for these obstetric emergencies, which includes triage and transferring patients to higher-level facilities, if necessary.”
Ob.gyns. and hospitals should have an organized and systematic treatment plan for postpartum hemorrhage, according to an updated practice bulletin from the American College of Obstetricians and Gynecologists (ACOG).
ACOG is recommending that obstetric care facilities post guidelines regarding the diagnosis methods and management techniques of postpartum hemorrhage. If postpartum hemorrhage is suspected, a physical exam should be performed to quickly inspect the uterus, cervix, vulva, and perineum to identify the source of bleeding. Once the cause has been identified, a treatment plan specific to the etiology of the bleeding can be implemented (Obstet Gynecol. 2017;130:e168-86).
“Less invasive methods should always be used first,” Aaron Caughey, MD, PhD, one of the coauthors of the practice bulletin, said in a statement. “If those methods fail, then more aggressive interventions must be considered to preserve the life of the mother.”
The ACOG reVITALize program defines postpartum hemorrhage “as cumulative blood loss greater than or equal to 1,000 mL or blood loss accompanied by signs or symptoms of hypovolemia within 24 hours after the birth process,” which differs from more traditional definitions of postpartum hemorrhage that puts the blood loss at more than 500 mL after vaginal birth and more than 1,000 mL after cesarean delivery.
The unpredictable nature of postpartum hemorrhage and its potential for severe morbidity and mortality make identifying its risk factors a priority. Risk assessment tools have been shown to identify 60%-85% of patients who will experience a serious hemorrhagic event. Risk factors for postpartum hemorrhage can be made into a simple table that categorizes different factors into low, medium, or high risk categories and posted in obstetric care facilities.
“The important thing is for providers to be able to recognize the signs and symptoms of excessive blood loss earlier and to have the resources at hand for the prompt escalation to more aggressive interventions if other therapies fail,” said Dr. Caughey, professor and chair of obstetrics and gynecology at Oregon Health and Science University, Portland.
Prevention is one of the key strategies outlined for combating postpartum hemorrhage. Many clinicians and organizations advise active management of the third stage of labor to decrease the likelihood of women experiencing postpartum hemorrhage. This can be done by administering oxytocin, massaging the uterus, and traction of the umbilical cord. Oxytocin can be administered both intravenously and intramuscularly and presents the lowest risk of adverse affects.
“By implementing standard protocols, we can improve outcomes,” Dr. Caughey said. “And this is even more critical for rural hospitals that often do not have the ability to treat a woman who may need a massive blood transfusion. They need to have a response plan in place for these obstetric emergencies, which includes triage and transferring patients to higher-level facilities, if necessary.”
Ob.gyns. and hospitals should have an organized and systematic treatment plan for postpartum hemorrhage, according to an updated practice bulletin from the American College of Obstetricians and Gynecologists (ACOG).
ACOG is recommending that obstetric care facilities post guidelines regarding the diagnosis methods and management techniques of postpartum hemorrhage. If postpartum hemorrhage is suspected, a physical exam should be performed to quickly inspect the uterus, cervix, vulva, and perineum to identify the source of bleeding. Once the cause has been identified, a treatment plan specific to the etiology of the bleeding can be implemented (Obstet Gynecol. 2017;130:e168-86).
“Less invasive methods should always be used first,” Aaron Caughey, MD, PhD, one of the coauthors of the practice bulletin, said in a statement. “If those methods fail, then more aggressive interventions must be considered to preserve the life of the mother.”
The ACOG reVITALize program defines postpartum hemorrhage “as cumulative blood loss greater than or equal to 1,000 mL or blood loss accompanied by signs or symptoms of hypovolemia within 24 hours after the birth process,” which differs from more traditional definitions of postpartum hemorrhage that puts the blood loss at more than 500 mL after vaginal birth and more than 1,000 mL after cesarean delivery.
The unpredictable nature of postpartum hemorrhage and its potential for severe morbidity and mortality make identifying its risk factors a priority. Risk assessment tools have been shown to identify 60%-85% of patients who will experience a serious hemorrhagic event. Risk factors for postpartum hemorrhage can be made into a simple table that categorizes different factors into low, medium, or high risk categories and posted in obstetric care facilities.
“The important thing is for providers to be able to recognize the signs and symptoms of excessive blood loss earlier and to have the resources at hand for the prompt escalation to more aggressive interventions if other therapies fail,” said Dr. Caughey, professor and chair of obstetrics and gynecology at Oregon Health and Science University, Portland.
Prevention is one of the key strategies outlined for combating postpartum hemorrhage. Many clinicians and organizations advise active management of the third stage of labor to decrease the likelihood of women experiencing postpartum hemorrhage. This can be done by administering oxytocin, massaging the uterus, and traction of the umbilical cord. Oxytocin can be administered both intravenously and intramuscularly and presents the lowest risk of adverse affects.
“By implementing standard protocols, we can improve outcomes,” Dr. Caughey said. “And this is even more critical for rural hospitals that often do not have the ability to treat a woman who may need a massive blood transfusion. They need to have a response plan in place for these obstetric emergencies, which includes triage and transferring patients to higher-level facilities, if necessary.”
FROM OBSTETRICS & GYNECOLOGY
Docs, insurers condemn latest ‘repeal and replace’ plan
Medical societies and insurers are voicing their opposition to legislation that would alter provisions of the Affordable Care Act and fundamentally change how Medicaid is funded.
The bill, introduced by Sen. Lindsey Graham (R-S.C.), Sen. Bill Cassidy (R-La.), Sen. Dean Heller (R-Nev.), and Sen. Ron Johnson (R-Wis.), features a number of provisions long sought by the GOP, including the repeal of the individual and employer mandates, repeal of individual tax credits as of 2020, and repeal of the medical device tax. The bill also would promote the use of health savings accounts and turn Medicaid funding into a block grant program, allowing states to implement policies such as work requirements.
James L. Madara, MD, CEO of the American Medical Association, told congressional leaders in a Sept. 19 letter that the bill would violate the precept of “first do no harm” and results in millions of Americans losing their health coverage. Additionally, it would destabilize health insurance markets and decrease access to affordable coverage.
“We are also concerned that the proposal would convert the Medicaid program into a system that limits federal support to care for needy patients to an insufficient predetermined formula based on per capita caps,” Dr. Madara continued. “Per capita caps fail to take into account unanticipated costs of new medical innovations or the fiscal impact of public health epidemics, such as the crisis of opioid abuse currently ravaging our nation. In addition, the amendment does not take steps toward coverage and access for all Americans, and while insurers are still required to offer coverage to patients with preexisting conditions, allowing states to get waivers to vary premiums based on health status would allow insurers to charge unaffordable premiums based on those preexisting conditions. Also, waivers of essential health benefits will mean patients may not have access to coverage for services pertinent to treating their conditions.”
The American Congress of Obstetricians and Gynecologists called the bill an “assault on women’s health.” The bill would end guaranteed insurance coverage of maternity care and women’s health preventive services, including cancer screenings and contraception, ACOG president Haywood Brown, MD, said in a statement.
Dr. Brown added that the bill “jeopardizes access to care for women with high-risk and expensive pregnancies, such as those with Zika virus, opioid use disorder, and preeclampsia. It further obstructs safety net patients’ access to care by forbidding Planned Parenthood’s participation in the Medicaid program.”
Doctors aren’t the only ones objecting to the GOP legislation. America’s Health Insurance Plans president and CEO Marilyn Tavenner said in a Sept. 20 letter to Congress that the bill would further destabilize the individual health insurance market.
The bill’s road to passage is far from certain. Once again, the GOP is aiming to use the budget reconciliation process to pass this legislation, which means it needs only a simple majority to pass (a minimum of 50 votes with Vice President Mike Pence offering the tiebreaker if the bill cannot get 51 votes). But even getting to 50 votes is going to be a challenge as the last attempt to pass similar repeal and replace language failed when Sen. Susan Collins (R-Maine), Sen. Lisa Murkowski (R-Alaska), and Sen. John McCain (R-Ariz.) voted that package down. Given the similar features, Sen. Collins and Sen. Murkowski may still oppose the bill, while Sen. Rand Paul (R-Ky.) has been vocal about his displeasure with the bill and other GOP senators are getting pressure from their state governors to oppose the bill.
The Senate Finance Committee has scheduled a Sept. 25 hearing to consider the bill, but as of press time, no witnesses have been announced, and the bill likely will not follow the regular order of allowing for amendments by committee members prior to its introduction on the Senate floor later that week.
Based on current budget rules, the bill must be passed by Sept. 30 in order for the budget reconciliation process to be used and to allow for passage with a simple majority. If the Senate is able to pass the bill, House Speaker Paul Ryan (R-Wisc.) has said he will bring it up in the House. President Trump has indicated he will sign it into law if it reaches his desk.
Medical societies and insurers are voicing their opposition to legislation that would alter provisions of the Affordable Care Act and fundamentally change how Medicaid is funded.
The bill, introduced by Sen. Lindsey Graham (R-S.C.), Sen. Bill Cassidy (R-La.), Sen. Dean Heller (R-Nev.), and Sen. Ron Johnson (R-Wis.), features a number of provisions long sought by the GOP, including the repeal of the individual and employer mandates, repeal of individual tax credits as of 2020, and repeal of the medical device tax. The bill also would promote the use of health savings accounts and turn Medicaid funding into a block grant program, allowing states to implement policies such as work requirements.
James L. Madara, MD, CEO of the American Medical Association, told congressional leaders in a Sept. 19 letter that the bill would violate the precept of “first do no harm” and results in millions of Americans losing their health coverage. Additionally, it would destabilize health insurance markets and decrease access to affordable coverage.
“We are also concerned that the proposal would convert the Medicaid program into a system that limits federal support to care for needy patients to an insufficient predetermined formula based on per capita caps,” Dr. Madara continued. “Per capita caps fail to take into account unanticipated costs of new medical innovations or the fiscal impact of public health epidemics, such as the crisis of opioid abuse currently ravaging our nation. In addition, the amendment does not take steps toward coverage and access for all Americans, and while insurers are still required to offer coverage to patients with preexisting conditions, allowing states to get waivers to vary premiums based on health status would allow insurers to charge unaffordable premiums based on those preexisting conditions. Also, waivers of essential health benefits will mean patients may not have access to coverage for services pertinent to treating their conditions.”
The American Congress of Obstetricians and Gynecologists called the bill an “assault on women’s health.” The bill would end guaranteed insurance coverage of maternity care and women’s health preventive services, including cancer screenings and contraception, ACOG president Haywood Brown, MD, said in a statement.
Dr. Brown added that the bill “jeopardizes access to care for women with high-risk and expensive pregnancies, such as those with Zika virus, opioid use disorder, and preeclampsia. It further obstructs safety net patients’ access to care by forbidding Planned Parenthood’s participation in the Medicaid program.”
Doctors aren’t the only ones objecting to the GOP legislation. America’s Health Insurance Plans president and CEO Marilyn Tavenner said in a Sept. 20 letter to Congress that the bill would further destabilize the individual health insurance market.
The bill’s road to passage is far from certain. Once again, the GOP is aiming to use the budget reconciliation process to pass this legislation, which means it needs only a simple majority to pass (a minimum of 50 votes with Vice President Mike Pence offering the tiebreaker if the bill cannot get 51 votes). But even getting to 50 votes is going to be a challenge as the last attempt to pass similar repeal and replace language failed when Sen. Susan Collins (R-Maine), Sen. Lisa Murkowski (R-Alaska), and Sen. John McCain (R-Ariz.) voted that package down. Given the similar features, Sen. Collins and Sen. Murkowski may still oppose the bill, while Sen. Rand Paul (R-Ky.) has been vocal about his displeasure with the bill and other GOP senators are getting pressure from their state governors to oppose the bill.
The Senate Finance Committee has scheduled a Sept. 25 hearing to consider the bill, but as of press time, no witnesses have been announced, and the bill likely will not follow the regular order of allowing for amendments by committee members prior to its introduction on the Senate floor later that week.
Based on current budget rules, the bill must be passed by Sept. 30 in order for the budget reconciliation process to be used and to allow for passage with a simple majority. If the Senate is able to pass the bill, House Speaker Paul Ryan (R-Wisc.) has said he will bring it up in the House. President Trump has indicated he will sign it into law if it reaches his desk.
Medical societies and insurers are voicing their opposition to legislation that would alter provisions of the Affordable Care Act and fundamentally change how Medicaid is funded.
The bill, introduced by Sen. Lindsey Graham (R-S.C.), Sen. Bill Cassidy (R-La.), Sen. Dean Heller (R-Nev.), and Sen. Ron Johnson (R-Wis.), features a number of provisions long sought by the GOP, including the repeal of the individual and employer mandates, repeal of individual tax credits as of 2020, and repeal of the medical device tax. The bill also would promote the use of health savings accounts and turn Medicaid funding into a block grant program, allowing states to implement policies such as work requirements.
James L. Madara, MD, CEO of the American Medical Association, told congressional leaders in a Sept. 19 letter that the bill would violate the precept of “first do no harm” and results in millions of Americans losing their health coverage. Additionally, it would destabilize health insurance markets and decrease access to affordable coverage.
“We are also concerned that the proposal would convert the Medicaid program into a system that limits federal support to care for needy patients to an insufficient predetermined formula based on per capita caps,” Dr. Madara continued. “Per capita caps fail to take into account unanticipated costs of new medical innovations or the fiscal impact of public health epidemics, such as the crisis of opioid abuse currently ravaging our nation. In addition, the amendment does not take steps toward coverage and access for all Americans, and while insurers are still required to offer coverage to patients with preexisting conditions, allowing states to get waivers to vary premiums based on health status would allow insurers to charge unaffordable premiums based on those preexisting conditions. Also, waivers of essential health benefits will mean patients may not have access to coverage for services pertinent to treating their conditions.”
The American Congress of Obstetricians and Gynecologists called the bill an “assault on women’s health.” The bill would end guaranteed insurance coverage of maternity care and women’s health preventive services, including cancer screenings and contraception, ACOG president Haywood Brown, MD, said in a statement.
Dr. Brown added that the bill “jeopardizes access to care for women with high-risk and expensive pregnancies, such as those with Zika virus, opioid use disorder, and preeclampsia. It further obstructs safety net patients’ access to care by forbidding Planned Parenthood’s participation in the Medicaid program.”
Doctors aren’t the only ones objecting to the GOP legislation. America’s Health Insurance Plans president and CEO Marilyn Tavenner said in a Sept. 20 letter to Congress that the bill would further destabilize the individual health insurance market.
The bill’s road to passage is far from certain. Once again, the GOP is aiming to use the budget reconciliation process to pass this legislation, which means it needs only a simple majority to pass (a minimum of 50 votes with Vice President Mike Pence offering the tiebreaker if the bill cannot get 51 votes). But even getting to 50 votes is going to be a challenge as the last attempt to pass similar repeal and replace language failed when Sen. Susan Collins (R-Maine), Sen. Lisa Murkowski (R-Alaska), and Sen. John McCain (R-Ariz.) voted that package down. Given the similar features, Sen. Collins and Sen. Murkowski may still oppose the bill, while Sen. Rand Paul (R-Ky.) has been vocal about his displeasure with the bill and other GOP senators are getting pressure from their state governors to oppose the bill.
The Senate Finance Committee has scheduled a Sept. 25 hearing to consider the bill, but as of press time, no witnesses have been announced, and the bill likely will not follow the regular order of allowing for amendments by committee members prior to its introduction on the Senate floor later that week.
Based on current budget rules, the bill must be passed by Sept. 30 in order for the budget reconciliation process to be used and to allow for passage with a simple majority. If the Senate is able to pass the bill, House Speaker Paul Ryan (R-Wisc.) has said he will bring it up in the House. President Trump has indicated he will sign it into law if it reaches his desk.
No difference in survival between x-ray or CT NSCLC follow-up
Madrid – Computed tomography scans do not appear to be superior to plain old chest x-rays for follow-up of patients with completely resected non–small cell lung cancer (NSCLC), results of a randomized clinical trial suggest.
Among 1,775 patients followed out to 10 years with either a “minimal” protocol – consisting of history, physical exam, and periodic chest x-rays – or a “maximal” protocol – including CT scans of the thorax and upper abdomen, as well as bronchoscopy for squamous-cell carcinomas – there were no significant differences in overall survival at either 3, 5, or 8 years of follow-up, reported Virginie Westeel, MD, from the Centre Hospitalier Régional Universitaire of the Hôpital Jean Minjoz in Besançon, France.
In hopes of finding that answer, Dr. Westeel and colleagues in the French Cooperative Thoracic Oncology Group conducted a clinical trial comparing the standard follow-up approach recommended in most clinical guidelines, as described by Dr. Westeel, with an experimental protocol consisting of history and exam plus chest x-ray, CT scans, and fiber-optic bronchoscopy (mandatory for squamous- and large-cell carcinomas, optional for adenocarcinomas).
Patients with completely resected stage I, II, and IIIA tumors, and T4 tumors with pulmonary nodules in the same lobe, were randomly assigned to follow-up with one of the two protocols.
In each trial arm, the assigned procedures were repeated every 6 months after randomization for the first 2 years, then yearly until 5 years.
After a median follow-up of 8.7 years, there was no significant difference in the primary endpoint of overall survival. Median OS was 123.6 months in the maximal protocol group, compared with 99.7 months in the minimal protocol group (P = .037)
The 3-, 5-, and 8-year survival rates for the maximal and minimal protocols, respectively, were 76.1% vs. 77.3%, 65.8% vs. 66.7%, and 54.6% vs. 51.7%.
Because there appeared to be a separation of the survival curve beginning around 8 years, the investigators performed an exploratory 2-year landmark analysis.
They found that, among patients who had a recurrence within 24 months of randomization, there was no difference in OS between each follow-up protocol. However, among those patients with no recurrence within 24 months of resection, the median OS was not reached among patients assigned to the maximal protocol versus 129.3 months for those assigned to the minimal protocol (P = .04).
Patients without early recurrence had higher rates of secondary primary cancers, and for these patients, early detection with CT-based surveillance could explain the differences in overall survival, Dr. Westeel said.
“Our suggestion for practice is that, because there is no survival difference, both follow-up protocols are acceptable. However, a CT scan every 6 months is probably of no value in the first 2 years,” but yearly chest CTs to detect second primary cancers early may be of interest, she said.
Enriqueta Felip, MD, from Vall D’Hebron Institute of Oncology in Barcelona, who was not involved in the trial, commented that, while the study needed to be conducted, it was unlikely to change her clinical practice because of potential differences among patients with varying stages of NSCLC at the time of resection.
“I think it’s an important trial, [but] tomorrow I will follow my patients with a CT scan,” she said.
Dr. Felip was an invited expert at the briefing.
The study was supported by the French Ministry of Health, Fondation de France, and Laboratoire Lilly. Dr. Westeel and Dr. Felip reported no conflicts of interest relevant to the study.
Madrid – Computed tomography scans do not appear to be superior to plain old chest x-rays for follow-up of patients with completely resected non–small cell lung cancer (NSCLC), results of a randomized clinical trial suggest.
Among 1,775 patients followed out to 10 years with either a “minimal” protocol – consisting of history, physical exam, and periodic chest x-rays – or a “maximal” protocol – including CT scans of the thorax and upper abdomen, as well as bronchoscopy for squamous-cell carcinomas – there were no significant differences in overall survival at either 3, 5, or 8 years of follow-up, reported Virginie Westeel, MD, from the Centre Hospitalier Régional Universitaire of the Hôpital Jean Minjoz in Besançon, France.
In hopes of finding that answer, Dr. Westeel and colleagues in the French Cooperative Thoracic Oncology Group conducted a clinical trial comparing the standard follow-up approach recommended in most clinical guidelines, as described by Dr. Westeel, with an experimental protocol consisting of history and exam plus chest x-ray, CT scans, and fiber-optic bronchoscopy (mandatory for squamous- and large-cell carcinomas, optional for adenocarcinomas).
Patients with completely resected stage I, II, and IIIA tumors, and T4 tumors with pulmonary nodules in the same lobe, were randomly assigned to follow-up with one of the two protocols.
In each trial arm, the assigned procedures were repeated every 6 months after randomization for the first 2 years, then yearly until 5 years.
After a median follow-up of 8.7 years, there was no significant difference in the primary endpoint of overall survival. Median OS was 123.6 months in the maximal protocol group, compared with 99.7 months in the minimal protocol group (P = .037)
The 3-, 5-, and 8-year survival rates for the maximal and minimal protocols, respectively, were 76.1% vs. 77.3%, 65.8% vs. 66.7%, and 54.6% vs. 51.7%.
Because there appeared to be a separation of the survival curve beginning around 8 years, the investigators performed an exploratory 2-year landmark analysis.
They found that, among patients who had a recurrence within 24 months of randomization, there was no difference in OS between each follow-up protocol. However, among those patients with no recurrence within 24 months of resection, the median OS was not reached among patients assigned to the maximal protocol versus 129.3 months for those assigned to the minimal protocol (P = .04).
Patients without early recurrence had higher rates of secondary primary cancers, and for these patients, early detection with CT-based surveillance could explain the differences in overall survival, Dr. Westeel said.
“Our suggestion for practice is that, because there is no survival difference, both follow-up protocols are acceptable. However, a CT scan every 6 months is probably of no value in the first 2 years,” but yearly chest CTs to detect second primary cancers early may be of interest, she said.
Enriqueta Felip, MD, from Vall D’Hebron Institute of Oncology in Barcelona, who was not involved in the trial, commented that, while the study needed to be conducted, it was unlikely to change her clinical practice because of potential differences among patients with varying stages of NSCLC at the time of resection.
“I think it’s an important trial, [but] tomorrow I will follow my patients with a CT scan,” she said.
Dr. Felip was an invited expert at the briefing.
The study was supported by the French Ministry of Health, Fondation de France, and Laboratoire Lilly. Dr. Westeel and Dr. Felip reported no conflicts of interest relevant to the study.
Madrid – Computed tomography scans do not appear to be superior to plain old chest x-rays for follow-up of patients with completely resected non–small cell lung cancer (NSCLC), results of a randomized clinical trial suggest.
Among 1,775 patients followed out to 10 years with either a “minimal” protocol – consisting of history, physical exam, and periodic chest x-rays – or a “maximal” protocol – including CT scans of the thorax and upper abdomen, as well as bronchoscopy for squamous-cell carcinomas – there were no significant differences in overall survival at either 3, 5, or 8 years of follow-up, reported Virginie Westeel, MD, from the Centre Hospitalier Régional Universitaire of the Hôpital Jean Minjoz in Besançon, France.
In hopes of finding that answer, Dr. Westeel and colleagues in the French Cooperative Thoracic Oncology Group conducted a clinical trial comparing the standard follow-up approach recommended in most clinical guidelines, as described by Dr. Westeel, with an experimental protocol consisting of history and exam plus chest x-ray, CT scans, and fiber-optic bronchoscopy (mandatory for squamous- and large-cell carcinomas, optional for adenocarcinomas).
Patients with completely resected stage I, II, and IIIA tumors, and T4 tumors with pulmonary nodules in the same lobe, were randomly assigned to follow-up with one of the two protocols.
In each trial arm, the assigned procedures were repeated every 6 months after randomization for the first 2 years, then yearly until 5 years.
After a median follow-up of 8.7 years, there was no significant difference in the primary endpoint of overall survival. Median OS was 123.6 months in the maximal protocol group, compared with 99.7 months in the minimal protocol group (P = .037)
The 3-, 5-, and 8-year survival rates for the maximal and minimal protocols, respectively, were 76.1% vs. 77.3%, 65.8% vs. 66.7%, and 54.6% vs. 51.7%.
Because there appeared to be a separation of the survival curve beginning around 8 years, the investigators performed an exploratory 2-year landmark analysis.
They found that, among patients who had a recurrence within 24 months of randomization, there was no difference in OS between each follow-up protocol. However, among those patients with no recurrence within 24 months of resection, the median OS was not reached among patients assigned to the maximal protocol versus 129.3 months for those assigned to the minimal protocol (P = .04).
Patients without early recurrence had higher rates of secondary primary cancers, and for these patients, early detection with CT-based surveillance could explain the differences in overall survival, Dr. Westeel said.
“Our suggestion for practice is that, because there is no survival difference, both follow-up protocols are acceptable. However, a CT scan every 6 months is probably of no value in the first 2 years,” but yearly chest CTs to detect second primary cancers early may be of interest, she said.
Enriqueta Felip, MD, from Vall D’Hebron Institute of Oncology in Barcelona, who was not involved in the trial, commented that, while the study needed to be conducted, it was unlikely to change her clinical practice because of potential differences among patients with varying stages of NSCLC at the time of resection.
“I think it’s an important trial, [but] tomorrow I will follow my patients with a CT scan,” she said.
Dr. Felip was an invited expert at the briefing.
The study was supported by the French Ministry of Health, Fondation de France, and Laboratoire Lilly. Dr. Westeel and Dr. Felip reported no conflicts of interest relevant to the study.
AT ESMO 2017
Key clinical point: There were no differences in long-term overall survival among patients with resected NSCLC followed with x-rays and those followed with CT scans.
Major finding: Overall survival rates at 3, 5, and 8 years were similar among patients followed with minimal or maximal protocols.
Data source: Randomized controlled trial in 1,775 patients with completely resected non–small cell lung cancer.
Disclosures: The study was supported by the French Ministry of Health, Fondation de France, and Laboratoire Lilly. Dr. Westeel and Dr. Felip reported no conflicts of interest relevant to the study.
When is it really recurrent strep throat?
CHICAGO – When a child is sitting in your exam room with recurrent strep pharyngitis, the first question to ask yourself is “Is it real?”
According to pediatric infectious disease specialist John Bradley, MD, the answer to that question comes with careful attention to the history and clinical presentation, but titers and viral polymerase chain reaction tests can also help clarify the diagnosis.
Although that involves some detective work and perhaps some legwork by the provider or the office staff, it’s worth the effort, especially in an era of increased concerns about antimicrobial stewardship, said Dr. Bradley during an antimicrobial update session at the annual meeting of the American Academy of Pediatrics.
“Are the episodes really documented by you in your office?” asked Dr. Bradley. If so, the job is easier. If not, it’s important to differentiate whether documentation of the strep infection was done by culture, whether it was done by an extremely sensitive rapid test, or whether any testing has been done at all, said Dr. Bradley, chief of the division of infectious diseases at the University of California, San Diego.
Somehow, said Dr. Bradley, it’s still true that all group A streptococci are susceptible to penicillin, but penicillin does not always work. There’s about a 10% failure rate for reasons that are not completely understood. Perhaps some individuals have other oropharyngeal flora that produce beta-lactamases, thereby negating penicillin’s efficacy against the strep, he added.
One very good clue as to whether the child has recurrent strep is the appearance of the throat, said Dr. Bradley. A viral illness also can produce a very red posterior oropharynx, so – unless there’s frank pus – it’s unlikely to be strep pharyngitis.
Some patients will, in fact, have recurrent strep, but some patients who might even have positive rapid strep tests may actually be carriers.
So, “what the heck is the carrier state?” asked Dr. Bradley. Although a rapid strep test will occasionally be positive, he explained, the culture is only weakly positive, with growth that’s usually less than 1+. The child who’s a carrier is not symptomatic, will not have an elevated antistreptolysin O titer, and is not contagious. Also, the child will not respond to penicillin treatment.
How can clinicians differentiate recurrent strep from a child with frequent viral illnesses who’s a carrier?
“For the standard case of ‘recurrent strep,’ please get cultures and document the density of group A strep to rule out the carrier state,” said Dr. Bradley. Having parents text pictures of the throat during an episode – for which his facility has a secure portal – can save families an office visit. A negative antistreptolysin O titer can help rule out a recurrent infection, he added.
When a child is having recurrent bouts of pharyngitis, but the clinical picture isn’t clearly consistent with strep, physicians can consider submitting multiplex viral polymerase chain reaction tests. “This can give the family an alternative diagnosis” and reassure parents that it’s safe to hold off on antibiotics, noted Dr. Bradley.
Culturing between episodes of pharyngitis, when the patient is asymptomatic, can also help determine whether a child is a carrier. Sometimes, it makes sense to culture the whole family, and there have also been reports of family pets being Group A strep reservoirs, said Dr. Bradley.
For recurrent infection, choose a broad spectrum agent that will knock back both Group A strep and the oral flora that may be producing beta-lactamases or adhesion molecules that negate penicillin’s efficacy. One logical choice is clindamycin for 10 days, although some strains are resistant. Another good choice is amoxicillin/clavulanate for 10 days or 10 days of a cephalosporin. Penicillin can still be used if it’s augmented by oral rifampin during the last 4 days of the 10-day course.
Long-term prophylaxis can also be considered for stubborn recurrences, he noted.
Dr. Bradley reported no relevant conflicts of interest.
CHICAGO – When a child is sitting in your exam room with recurrent strep pharyngitis, the first question to ask yourself is “Is it real?”
According to pediatric infectious disease specialist John Bradley, MD, the answer to that question comes with careful attention to the history and clinical presentation, but titers and viral polymerase chain reaction tests can also help clarify the diagnosis.
Although that involves some detective work and perhaps some legwork by the provider or the office staff, it’s worth the effort, especially in an era of increased concerns about antimicrobial stewardship, said Dr. Bradley during an antimicrobial update session at the annual meeting of the American Academy of Pediatrics.
“Are the episodes really documented by you in your office?” asked Dr. Bradley. If so, the job is easier. If not, it’s important to differentiate whether documentation of the strep infection was done by culture, whether it was done by an extremely sensitive rapid test, or whether any testing has been done at all, said Dr. Bradley, chief of the division of infectious diseases at the University of California, San Diego.
Somehow, said Dr. Bradley, it’s still true that all group A streptococci are susceptible to penicillin, but penicillin does not always work. There’s about a 10% failure rate for reasons that are not completely understood. Perhaps some individuals have other oropharyngeal flora that produce beta-lactamases, thereby negating penicillin’s efficacy against the strep, he added.
One very good clue as to whether the child has recurrent strep is the appearance of the throat, said Dr. Bradley. A viral illness also can produce a very red posterior oropharynx, so – unless there’s frank pus – it’s unlikely to be strep pharyngitis.
Some patients will, in fact, have recurrent strep, but some patients who might even have positive rapid strep tests may actually be carriers.
So, “what the heck is the carrier state?” asked Dr. Bradley. Although a rapid strep test will occasionally be positive, he explained, the culture is only weakly positive, with growth that’s usually less than 1+. The child who’s a carrier is not symptomatic, will not have an elevated antistreptolysin O titer, and is not contagious. Also, the child will not respond to penicillin treatment.
How can clinicians differentiate recurrent strep from a child with frequent viral illnesses who’s a carrier?
“For the standard case of ‘recurrent strep,’ please get cultures and document the density of group A strep to rule out the carrier state,” said Dr. Bradley. Having parents text pictures of the throat during an episode – for which his facility has a secure portal – can save families an office visit. A negative antistreptolysin O titer can help rule out a recurrent infection, he added.
When a child is having recurrent bouts of pharyngitis, but the clinical picture isn’t clearly consistent with strep, physicians can consider submitting multiplex viral polymerase chain reaction tests. “This can give the family an alternative diagnosis” and reassure parents that it’s safe to hold off on antibiotics, noted Dr. Bradley.
Culturing between episodes of pharyngitis, when the patient is asymptomatic, can also help determine whether a child is a carrier. Sometimes, it makes sense to culture the whole family, and there have also been reports of family pets being Group A strep reservoirs, said Dr. Bradley.
For recurrent infection, choose a broad spectrum agent that will knock back both Group A strep and the oral flora that may be producing beta-lactamases or adhesion molecules that negate penicillin’s efficacy. One logical choice is clindamycin for 10 days, although some strains are resistant. Another good choice is amoxicillin/clavulanate for 10 days or 10 days of a cephalosporin. Penicillin can still be used if it’s augmented by oral rifampin during the last 4 days of the 10-day course.
Long-term prophylaxis can also be considered for stubborn recurrences, he noted.
Dr. Bradley reported no relevant conflicts of interest.
CHICAGO – When a child is sitting in your exam room with recurrent strep pharyngitis, the first question to ask yourself is “Is it real?”
According to pediatric infectious disease specialist John Bradley, MD, the answer to that question comes with careful attention to the history and clinical presentation, but titers and viral polymerase chain reaction tests can also help clarify the diagnosis.
Although that involves some detective work and perhaps some legwork by the provider or the office staff, it’s worth the effort, especially in an era of increased concerns about antimicrobial stewardship, said Dr. Bradley during an antimicrobial update session at the annual meeting of the American Academy of Pediatrics.
“Are the episodes really documented by you in your office?” asked Dr. Bradley. If so, the job is easier. If not, it’s important to differentiate whether documentation of the strep infection was done by culture, whether it was done by an extremely sensitive rapid test, or whether any testing has been done at all, said Dr. Bradley, chief of the division of infectious diseases at the University of California, San Diego.
Somehow, said Dr. Bradley, it’s still true that all group A streptococci are susceptible to penicillin, but penicillin does not always work. There’s about a 10% failure rate for reasons that are not completely understood. Perhaps some individuals have other oropharyngeal flora that produce beta-lactamases, thereby negating penicillin’s efficacy against the strep, he added.
One very good clue as to whether the child has recurrent strep is the appearance of the throat, said Dr. Bradley. A viral illness also can produce a very red posterior oropharynx, so – unless there’s frank pus – it’s unlikely to be strep pharyngitis.
Some patients will, in fact, have recurrent strep, but some patients who might even have positive rapid strep tests may actually be carriers.
So, “what the heck is the carrier state?” asked Dr. Bradley. Although a rapid strep test will occasionally be positive, he explained, the culture is only weakly positive, with growth that’s usually less than 1+. The child who’s a carrier is not symptomatic, will not have an elevated antistreptolysin O titer, and is not contagious. Also, the child will not respond to penicillin treatment.
How can clinicians differentiate recurrent strep from a child with frequent viral illnesses who’s a carrier?
“For the standard case of ‘recurrent strep,’ please get cultures and document the density of group A strep to rule out the carrier state,” said Dr. Bradley. Having parents text pictures of the throat during an episode – for which his facility has a secure portal – can save families an office visit. A negative antistreptolysin O titer can help rule out a recurrent infection, he added.
When a child is having recurrent bouts of pharyngitis, but the clinical picture isn’t clearly consistent with strep, physicians can consider submitting multiplex viral polymerase chain reaction tests. “This can give the family an alternative diagnosis” and reassure parents that it’s safe to hold off on antibiotics, noted Dr. Bradley.
Culturing between episodes of pharyngitis, when the patient is asymptomatic, can also help determine whether a child is a carrier. Sometimes, it makes sense to culture the whole family, and there have also been reports of family pets being Group A strep reservoirs, said Dr. Bradley.
For recurrent infection, choose a broad spectrum agent that will knock back both Group A strep and the oral flora that may be producing beta-lactamases or adhesion molecules that negate penicillin’s efficacy. One logical choice is clindamycin for 10 days, although some strains are resistant. Another good choice is amoxicillin/clavulanate for 10 days or 10 days of a cephalosporin. Penicillin can still be used if it’s augmented by oral rifampin during the last 4 days of the 10-day course.
Long-term prophylaxis can also be considered for stubborn recurrences, he noted.
Dr. Bradley reported no relevant conflicts of interest.
EXPERT ANALYSIS FROM AAP 2017
AGA members meet with Rep. Gene Green at Baylor College
In-district meetings with congressional representatives provide a great opportunity for AGA members to establish working relationships with legislators, and help make the voices of our profession and our patients heard.
Members of the Baylor College of Medicine gastroenterology division – Avi Ketwaroo, MD; Richa Shukla, MD; Yamini Natarajan, MD; and Jordan Shapiro, MD – had the opportunity to meet with U.S. Rep. Gene Green, a Democrat from Texas’ 29th Congressional District, as part of AGA’s efforts to link constituents with local representatives. The group discussed the importance of supporting increases in NIH funding to maintain similar levels based on biomedical research inflation, the importance of screening colonoscopy, and improving access to care by opposing the repeal of the Affordable Care Act.
Watch an AGA webinar, available in the AGA Community resource library for AGA members only (community.gastro.org) to learn more about how to set up congressional meetings in your district or contact Navneet Buttar, AGA government and political affairs manager, at [email protected] or 240-482-3221.
[email protected]
In-district meetings with congressional representatives provide a great opportunity for AGA members to establish working relationships with legislators, and help make the voices of our profession and our patients heard.
Members of the Baylor College of Medicine gastroenterology division – Avi Ketwaroo, MD; Richa Shukla, MD; Yamini Natarajan, MD; and Jordan Shapiro, MD – had the opportunity to meet with U.S. Rep. Gene Green, a Democrat from Texas’ 29th Congressional District, as part of AGA’s efforts to link constituents with local representatives. The group discussed the importance of supporting increases in NIH funding to maintain similar levels based on biomedical research inflation, the importance of screening colonoscopy, and improving access to care by opposing the repeal of the Affordable Care Act.
Watch an AGA webinar, available in the AGA Community resource library for AGA members only (community.gastro.org) to learn more about how to set up congressional meetings in your district or contact Navneet Buttar, AGA government and political affairs manager, at [email protected] or 240-482-3221.
[email protected]
In-district meetings with congressional representatives provide a great opportunity for AGA members to establish working relationships with legislators, and help make the voices of our profession and our patients heard.
Members of the Baylor College of Medicine gastroenterology division – Avi Ketwaroo, MD; Richa Shukla, MD; Yamini Natarajan, MD; and Jordan Shapiro, MD – had the opportunity to meet with U.S. Rep. Gene Green, a Democrat from Texas’ 29th Congressional District, as part of AGA’s efforts to link constituents with local representatives. The group discussed the importance of supporting increases in NIH funding to maintain similar levels based on biomedical research inflation, the importance of screening colonoscopy, and improving access to care by opposing the repeal of the Affordable Care Act.
Watch an AGA webinar, available in the AGA Community resource library for AGA members only (community.gastro.org) to learn more about how to set up congressional meetings in your district or contact Navneet Buttar, AGA government and political affairs manager, at [email protected] or 240-482-3221.
[email protected]
AGA comments on Quality Payment proposed rule
AGA provided comments on a proposed rule describing potential changes to the Quality Payment Program (QPP) established under the Medicare Access and CHIP Reauthorization Act (MACRA) for the 2018 performance year. AGA thanks the many members who also submitted comments to CMS to tell the agency how proposed changes will impact you.
For year two, CMS proposed many policies that increase flexibility and incentives under the QPP. However, many proposals target solo practitioners, small practices, and other eligible clinicians with special circumstances. While we support these proposals, AGA’s comments to CMS also ask for changes that are needed to make the QPP work for all gastroenterologists, such as reducing the number of points needed to avoid a payment penalty.
CMS will finalize changes to the QPP during the fall of 2017. Final changes will take effect with the performance period that begins on Jan. 1, 2018. Performance during 2018 will impact payment for services in 2020. AGA members will be notified as soon as the rule is made available by CMS.
Still unsure how to participate in year one?
Make sure your practice is prepared for the 2017 performance year. If you are eligible to participate in 2017, but choose not to, your rates will decrease by 4% in 2019. AGA’s MACRA resource center provides customized advice based on your practice situation to get you on track. It’s not too late to start, but if you wait until Oct. 2, 2017, the deadline to start submitting claims, it will be. Get started now, http://www.gastro.org/macra.
AGA provided comments on a proposed rule describing potential changes to the Quality Payment Program (QPP) established under the Medicare Access and CHIP Reauthorization Act (MACRA) for the 2018 performance year. AGA thanks the many members who also submitted comments to CMS to tell the agency how proposed changes will impact you.
For year two, CMS proposed many policies that increase flexibility and incentives under the QPP. However, many proposals target solo practitioners, small practices, and other eligible clinicians with special circumstances. While we support these proposals, AGA’s comments to CMS also ask for changes that are needed to make the QPP work for all gastroenterologists, such as reducing the number of points needed to avoid a payment penalty.
CMS will finalize changes to the QPP during the fall of 2017. Final changes will take effect with the performance period that begins on Jan. 1, 2018. Performance during 2018 will impact payment for services in 2020. AGA members will be notified as soon as the rule is made available by CMS.
Still unsure how to participate in year one?
Make sure your practice is prepared for the 2017 performance year. If you are eligible to participate in 2017, but choose not to, your rates will decrease by 4% in 2019. AGA’s MACRA resource center provides customized advice based on your practice situation to get you on track. It’s not too late to start, but if you wait until Oct. 2, 2017, the deadline to start submitting claims, it will be. Get started now, http://www.gastro.org/macra.
AGA provided comments on a proposed rule describing potential changes to the Quality Payment Program (QPP) established under the Medicare Access and CHIP Reauthorization Act (MACRA) for the 2018 performance year. AGA thanks the many members who also submitted comments to CMS to tell the agency how proposed changes will impact you.
For year two, CMS proposed many policies that increase flexibility and incentives under the QPP. However, many proposals target solo practitioners, small practices, and other eligible clinicians with special circumstances. While we support these proposals, AGA’s comments to CMS also ask for changes that are needed to make the QPP work for all gastroenterologists, such as reducing the number of points needed to avoid a payment penalty.
CMS will finalize changes to the QPP during the fall of 2017. Final changes will take effect with the performance period that begins on Jan. 1, 2018. Performance during 2018 will impact payment for services in 2020. AGA members will be notified as soon as the rule is made available by CMS.
Still unsure how to participate in year one?
Make sure your practice is prepared for the 2017 performance year. If you are eligible to participate in 2017, but choose not to, your rates will decrease by 4% in 2019. AGA’s MACRA resource center provides customized advice based on your practice situation to get you on track. It’s not too late to start, but if you wait until Oct. 2, 2017, the deadline to start submitting claims, it will be. Get started now, http://www.gastro.org/macra.
How to manage bleeding in patients taking direct oral anticoagulants (DOACs)
Case
A 72-year-old man with a history of nonvalvular atrial fibrillation (AF) and hypertension presents to the ER after an episode of hematochezia. He is prescribed dabigatran 150 mg twice daily for his AF and took his evening dose 2 hours prior to presentation. His initial exam reveals vital signs of BP 120/55, HR 105, RR 14 and bright red stool on rectal exam. His hemoglobin is 8.1 g/dL, down from 12.0 g/dL one month ago. He has normal renal function. How should you manage his gastrointestinal bleeding?
Background
Direct oral anticoagulants (DOACs) consist of two classes of drugs: oral factor Xa inhibitors (apixaban, edoxaban, and rivaroxaban) and direct thrombin inhibitors (dabigatran). They have gained substantial popularity since their commercial introduction in 2010, and are now Food and Drug Administration approved for the treatment of atrial fibrillation (AF) and venous thromboembolism (VTE) in noncancer patients. DOAC use will likely increase given favorable safety profiles, reliable pharmacokinetics, and recent guidelines recommending their use over vitamin K antagonists (VKAs) for treatment of VTE in noncancer patients.1
A primary concern about the routine use of DOACs has been the lack of commercially available direct reversal agents. Unlike warfarin, which has an effective rapid antidote, no direct reversal agent is available for Xa inhibitors, and only recently has there been FDA approval for idarucizumab, a direct thrombin inhibitor reversal drug. Therefore, clinicians are often left wondering how to manage bleeding episodes in patients receiving DOACs.
Literature review
What is the risk of bleeding for patients taking DOACs?
DOACs carry a low but significant risk of bleeding, including life-threatening bleeding. There is now robust data from over 100,000 patients in randomized clinical trials of nonvalvular AF and VTE comparing the risk of major and fatal bleeding between DOACs and VKAs.2 These trials reveal an annual major bleeding rate of 2%-4% in patients with AF and 1%-2% in patients with VTE taking DOACs.
Importantly, DOACs were found to carry a statistically lower risk of major and fatal bleeding than VKAs. Patients taking DOACs have a relative risk of major bleeding of 0.72, compared with VKAs, and a RR of fatal bleeding of 0.53. Additionally, the case fatality rate for major bleeding episodes was 7.6% for DOACs versus 11.0% for warfarin, despite not having an available antidote for DOACs in these trials.3 Although there is an increased risk of bleeding from DOACs, the rates of major bleeding and of serious complications from bleeding are lower than with warfarin.
How long does the effect of a DOAC last?
A significant advantage of DOACs over VKAs in the setting of bleeding is their shorter half-lives, which range from a low estimate of 5 hours for rivaroxaban to a high estimate of 17 hours for dabigatran4-8 (Table 1). Given that it takes 4-5 half-lives for a drug to be functionally eliminated, coagulation typically normalizes in patients taking DOACs within 1-3 days, compared with 3-5 days for warfarin. All DOACs have significant renal clearance, and renal failure will prolong the duration of anticoagulation. For patients who are taking DOACs and present with bleeding, it is important to assess their renal function.
Are coagulation tests helpful when assessing the effect of DOACs?
Prothrombin time (PT/INR) and activated partial thromboplastin time (aPTT) should be measured in all patients presenting with significant bleeding, whether or not the patient is taking a DOAC. PT and aPTT are commonly elevated for patients taking direct thrombin inhibitors and Xa inhibitors. Although a prolonged PT and/or aPTT can be useful in determining if the anticoagulant effect from DOACs is still present, normal values of these tests do not rule out an anticoagulant effect in patients taking DOACs.9,10 Thrombin Time (TT) is a widely available test with quick results, and a normal value rules out the therapeutic effect of dabigatran. Finally, the anti–factor Xa assay is a sensitive test for Xa inhibitors, but requires calibration to the DOAC of interest in order to be reliable. Clinicians should consult with their institution’s laboratory prior to using an anti–factor Xa level to test the anticoagulant effect of a specific DOAC. Repeat coagulation testing may be useful in some clinical circumstances, especially if a patient has renal impairment.
Are there reversal agents for DOACs?
In October 2015, the FDA approved idarucizumab, a monoclonal antibody fragment that binds dabigatran with much greater affinity than thrombin, thus quickly reversing the effect of the direct thrombin inhibitor. FDA approval came in response to an interim analysis of an ongoing open-label trial, RE-VERSE AD.11 This study enrolled 90 adults with major bleeding or need for an emergency procedure taking dabigatran to receive idarucizumab (2.5 g in 50 mL rapid infusion dose given twice less than 15 minutes apart for a total of 5 g). Idarucizumab immediately reversed the effect of dabigatran on clotting tests in 88%-98% of the patients. For patients with major bleeding, the median time for bleeding cessation was 11.4 hours. One thrombotic event was reported within 72 hours of drug administration. Therefore, in patients taking dabigatran with an elevated TT, idarucizumab may be used if the bleeding is life threatening and refractory to initial supportive measures.
There are no FDA-approved antidotes for the factor Xa inhibitors. One promising agent is andexanet-alfa, an inactivated form of factor Xa that irreversibly binds Xa inhibitors. The ongoing, open-label ANNEXA-4 trial12 reported a decrease in anti–factor Xa activity of ~90% after bolus administration of the drug followed by 2-hour infusion in 67 patients with life-threatening bleeding, with clinical hemostasis achieved in 79% in patients by 12 hours. However, thrombotic events occurred in 18% of the patients at 1 month. Additional safety and efficacy data, along with plans for postmarket surveillance, will be needed prior to approval for clinical use.
Are there other options to obtain hemostasis?
Clotting factor products, specifically fresh frozen plasma (FFP) and prothrombin complex concentrates (PCCs), are often used to attempt to reverse anticoagulation from DOACs. While FFP alone has no evidence to support its use in reversing the effect of DOACs, PCCs might reverse anticoagulation for both Xa inhibitors and direct thrombin inhibitors.13 Some experts recommend unactivated PCC over activated PCC because of a theoretically increased thrombotic risk of activated PCC.14 For patients taking Xa inhibitors or dabigatran (if idarucizumab is unavailable) with life-threatening bleeding, PCC should be used in an attempt to reverse the bleeding.
Another strategy to promote hemostasis in bleeding patients taking DOACs is to use antifibrinolytics. Effective for control of bleeding in trauma and surgical patients, tranexamic acid has not been widely studied in nonsurgical bleeding, much less DOAC-related nonsurgical bleeding. A 2014 Cochrane review of a small number of trials suggested a possible mortality benefit from its use in upper GI bleeding, but the quality of included trials was poor.15 The ongoing HALT-IT trial, enrolling 8,000 patients with gastrointestinal bleeding, aims to clarify the mortality benefit of tranexamic acid.16 Despite effectively promoting hemostasis in many populations of bleeding patients, tranexamic acid carries no discernible thrombotic risk.17,18 By preventing clot degradation through a downstream mechanism at low cost and risk, antifibrinolytics are a practical adjunctive therapy to control major bleeding in patients on DOACs.
Can charcoal or dialysis reduce the systemic concentration of DOACs?
In addition to discontinuing the DOAC, both charcoal and dialysis can reduce the systemic concentration of DOACs. If the ingestion was recent, oral activated charcoal can reduce the systemic absorption of DOACs. To date there are no data on the efficacy of charcoal in bleeding patients taking DOACs. However, in two recent trials, administration of a single dose of charcoal in healthy patients led to significantly decreased area under concentration-time curves (AUC) when given at 6 and 8 hours after ingestion of a therapeutic dose of apixaban and rivaroxaban, respectively.19,20 While further studies are needed to confirm its clinical benefit, charcoal is recommended for major bleeding when given within 2 hours of ingestion of a DOAC and may be useful within 8 hours.
Unlike charcoal, which can be used for patients on Xa inhibitors or dabigatran, hemodialysis is only effective for reducing serum concentrations of dabigatran because of its low plasma protein binding (~35%). A review of 35 patients (10 with normal renal function) with severe bleeding showed significant reductions in coagulation tests (aPTT, PT, TT) and dabigatran levels after hemodialysis.21 For severe bleeding episodes particularly in patients with impaired renal function, providers should consider the use of continuous renal replacement therapy until clinical hemostasis is achieved.
What is the expert’s opinion?
We asked one of our hematologists with expertise in DOACs for his opinion on this topic. Most patients with DOAC-associated bleeding can be managed with supportive care because of the short half-life of these agents in patients with reasonably preserved renal function. The main scenario for escalating therapy to PCC or idarucizumab is life-threatening bleeding, such as intracranial hemorrhage and gastrointestinal hemorrhage with hemodynamic instability. The threshold for use of idarucizumab for patients taking dabigatran with bleeding should be lower than PCCs because there is better evidence for clinical benefit with less risk.
Developing reversal agents continues to be costly, requiring extensive preclinical work and clinical trials that are difficult to do. Assuming that reversal agents become more affordable in the longer term, and safety profiles are better established, clinicians may eventually have a lower threshold for their use in a wider variety of bleeding episodes. Lastly, adverse outcomes often occur, not during the acute bleeding episode, but several weeks later in patients whose providers delay restarting anticoagulation. Thus, it is important to resume anticoagulant therapy as soon as it is safe to do so.
Back to the case
Our patient was given a 50-g suspension of oral activated charcoal, along with two doses of 1 g intravenous tranexamic acid 8 hours apart. He was typed and crossed for blood, and ultimately received 1 unit of packed red blood cells before stabilizing without other measures. His colonoscopy subsequently revealed a diverticular bleed with a visible vessel that was coagulated. He was discharged 2 days later after remaining clinically stable after colonoscopy.
Bottom line
For the majority of bleeding patients on DOACs, supportive care with transfusions and local hemostatic interventions to control bleeding will likely be sufficient. Because of the short half-lives of DOACs, most patients do not require additional therapy (Table 2), and these patients actually have better outcomes from major bleeding episodes than patients taking VKAs. Antifibrinolytics should be a first-line prohemostatic therapy in major bleeding. Oral activated charcoal may be effective within 2-8 hours after ingestion for reduction of serum DOAC concentrations. Finally, in cases of life-threatening bleeding, idarucizumab can be used to reverse anticoagulation for patients taking dabigatran. When idarucizumab is unavailable, or for patients taking Xa inhibitors, PCC can be used.
Dr. Hagan is chief medical resident at the University of Washington Medical Center in Seattle. Dr. Albert is clinical instructor of medicine at UWMC. Dr. Garcia is professor of medicine and associate medical director of antithrombotic therapy at UWMC. Dr. Huang is an attending with the UWMC Medicine Consult Service and assistant clinical professor in the division of general internal medicine at UW.
Key Points
• The risk of major bleeding, and the case fatality rate of major bleeding, is significantly lower in patients taking DOACs versus VKAs
• For the majority of patients with bleeding on DOACs, withholding anticoagulation and supportive care is sufficient
• Idarucizumab is a novel and effective antidote to dabigatran, but should be reserved for patients with life-threatening bleeding
• Patients with DOAC-associated bleeding should be restarted on anticoagulation as soon as it is safe to do so
Additional Reading
Management of bleeding in patients receiving direct oral anticoagulants. UpToDate 2016.
How do I treat target-specific oral anticoagulant-associated bleeding? Blood 2014.
References
1. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest. 2016;149(2):315-52.
2. Chai-adisaksopha C, Crowther M, Isayama T, Lim W. The impact of bleeding complications in patients receiving target-specific oral anticoagulants: a systematic review and meta-analysis. Blood. 2014;124(15):2450-8.
3. Chai-adisaksopha C, Hillis C, Isayama T, Lim W, Iorio A, Crowther M. Mortality outcomes in patients receiving direct oral anticoagulants: a systematic review and meta-analysis of randomized controlled trials. J Thromb Haemost. 2015;13(11):2012-20.
4. Savaysa (edoxaban) [package insert]. Daiichi Sankyo, Inc, Tokyo, Japan; 2015. www.accessdata.fda.gov/drugsatfda_docs/label/2015/206316lbl.pdf. Accessed January 8th, 2016.
5. Xarelto (rivaroxaban) [package insert]. Janssen Pharmaceuticals, Inc. Titusville, NJ; 2011. www.accessdata.fda.gov/drugsatfda_docs/label/2011/202439s001lbl.pdf. Accessed January 8th, 2016.
6. Pradaxa (dabigatran) [package insert]. Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield, CT; 2011. www.accessdata.fda.gov/drugsatfda_docs/label/2011/022512s007lbl.pdf. Accessed January 8th, 2016.
7. Eliquis (apixaban) [package insert]. Bristol-Myers Squibb Company, Princeton, NJ; 2012. www.accessdata.fda.gov/drugsatfda_docs/label/2012/202155s000lbl.pdf. Accessed January 8th, 2016.
8. Scaglione F. New oral anticoagulants: comparative pharmacology with vitamin K antagonists. Clin Pharmacokinet. 2013;52(2):69-82.
9. Tripodi A. The laboratory and the direct oral anticoagulants. Blood.
2013;121(20):4032-5.
10. Samuelson BT, Cuker A, Siegal DM, Crowther M, Garcia DA. Laboratory Assessment of the Anticoagulant Activity of Direct Oral Anticoagulants (DOACs): A Systematic Review. Chest. 2016;
11. Pollack CV, Reilly PA, Eikelboom J, et al. Idarucizumab for Dabigatran Reversal. N Engl J Med. 2015;373(6):511-20.
12. Connolly SJ, Milling TJ, Eikelboom JW, et al. Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors. N Engl J Med. 2016.
13. Dickneite G, Hoffman M. Reversing the new oral anticoagulants with prothrombin complex concentrates (PCCs): what is the evidence?. Thromb Haemost. 2014;111(2):189-98.
14. Sørensen B, Spahn DR, Innerhofer P, Spannagl M, Rossaint R. Clinical review: Prothrombin complex concentrates--evaluation of safety and thrombogenicity. Crit Care. 2011;15(1):201.
15. Bennett C, Klingenberg S, Langholz E, Gluud L. Tranexamic acid for upper gastrointestinal bleeding. Cochrane Database of Systematic Reviews 2014, Issue 11. Art. No.: CD006640.
16. Roberts I, Coats T, Edwards P, et al. HALT-IT – tranexamic acid for the treatment of gastrointestinal bleeding: study protocol for a randomised controlled trial. Trials. 2014 Nov 19;15:450.
17. Dyba J, Chan F, Lau K, Chan A, Chan H. Tranexamic Acid is a Weak Provoking Factor for Thromboembolic Events: A Systematic Review of the Literature. Blood. 2013; 122(21): 3629.
18. Myles PS, Smith JA, Forbes A, et al. Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery. N Engl J Med. 2016; 376(2):136-148.
19. Wang X, Mondal S, Wang J, et al. Effect of Activated Charcoal on Apixaban Pharmacokinetics in Healthy Subjects. American Journal of Cardiovascular Drugs. 2014;14(2):147-154.
20. Ollier E, Hodin S, Lanoiselée J, et al. Effect of Activated Charcoal on Rivaroxaban Complex Absorption. Clin Pharmacokinet. 2016 Dec 2.
21. Chai-adisaksopha C, Hillis C, Lim W, Boonyawat K, Moffat K, Crowther M. Hemodialysis for the treatment of dabigatran-associated bleeding: a case report and systematic review. J Thromb Haemost. 2015;13(10):1790-8.
22. Schulman S, Kearon C. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005;3(4):692-4.
23. UW Anticoagulation Services. UW Medicine Pharmacy Services Web site. 2014. Available at https://depts.washington.edu/anticoag, Accessed March 8, 2017.
________________________________________________________________________
Table 1: Pharmacologic Profiles of Xa and Direct Thrombin Inhibitors4-8, 23
tmax t1/2, CrCl 50-80 t1/2 CrCl < 30 Dialyzable?
Apixaban 3-4 h 15 h 17 h No
Dabigatran 1-3 h 17 h 28 h Yes
Edoxaban 1-2 h 10-14 h no data No
Rivaroxaban 2-4 h 9 h 10 h No
tmax = time to peak serum concentration after ingestion, t1/2= serum half-life, CrCl= creatinine clearance in mL/min
*Average values assuming normal hepatic function. Aside from dabigatran, which has minimal hepatic clearance, all other DOACs can have prolonged half-lives in hepatic impairment.
Table 2: Management of Bleeding Patients Taking DOACs
Direct Thrombin Inhibitors (dabigatran)
Xa inhibitors (apixaban, edoxaban, rivaroxaban)Minor Bleeding
• Withhold DOAC
• Local hemostatic measures
Major Bleeding*
All of the above, AND
• Antifibrinolytic if bleeding persists
• Restore physiologic perfusion
• Charcoal if last dose within 2-8 hours
• Transfusion indications:
o Red blood cells: anemia
o Platelets: antiplatelet agents or thrombocytopenia
o Plasma: coagulopathy (dilution, DIC, liver failure), not for DOAC reversal
Life-threatening Bleeding**
All of the above, AND:
• Idarucizumab (confirm anticoagulant effect with thrombin time first)
• If idarucizumab is unavailable, use PCC
• Consider hemodialysis until hemostasis achieved, especially if patient in renal failure
All of the above, AND:
• Unactivated PCC (if available and calibrated to specific Xa inhibitor, confirm anticoagulant effect with anti-Xa level)
* Adapted from the International Society on Thrombosis and Hemostasis: bleeding with a fall in hemoglobin level ≥ 2 g/dL, OR bleeding leading to ≥ 2 units of PRBC transfused.21 Clinicians should perform risk stratification of bleeding episodes using vital signs, laboratory results, the area of bleeding, and patient comorbidities.
**Uncontrolled bleeding, OR symptomatic bleeding in a critical area or organ (such as intracranial, intraocular, intraspinal, retroperitoneal, pericardial, or intramuscular with compartment syndrome).
Case
A 72-year-old man with a history of nonvalvular atrial fibrillation (AF) and hypertension presents to the ER after an episode of hematochezia. He is prescribed dabigatran 150 mg twice daily for his AF and took his evening dose 2 hours prior to presentation. His initial exam reveals vital signs of BP 120/55, HR 105, RR 14 and bright red stool on rectal exam. His hemoglobin is 8.1 g/dL, down from 12.0 g/dL one month ago. He has normal renal function. How should you manage his gastrointestinal bleeding?
Background
Direct oral anticoagulants (DOACs) consist of two classes of drugs: oral factor Xa inhibitors (apixaban, edoxaban, and rivaroxaban) and direct thrombin inhibitors (dabigatran). They have gained substantial popularity since their commercial introduction in 2010, and are now Food and Drug Administration approved for the treatment of atrial fibrillation (AF) and venous thromboembolism (VTE) in noncancer patients. DOAC use will likely increase given favorable safety profiles, reliable pharmacokinetics, and recent guidelines recommending their use over vitamin K antagonists (VKAs) for treatment of VTE in noncancer patients.1
A primary concern about the routine use of DOACs has been the lack of commercially available direct reversal agents. Unlike warfarin, which has an effective rapid antidote, no direct reversal agent is available for Xa inhibitors, and only recently has there been FDA approval for idarucizumab, a direct thrombin inhibitor reversal drug. Therefore, clinicians are often left wondering how to manage bleeding episodes in patients receiving DOACs.
Literature review
What is the risk of bleeding for patients taking DOACs?
DOACs carry a low but significant risk of bleeding, including life-threatening bleeding. There is now robust data from over 100,000 patients in randomized clinical trials of nonvalvular AF and VTE comparing the risk of major and fatal bleeding between DOACs and VKAs.2 These trials reveal an annual major bleeding rate of 2%-4% in patients with AF and 1%-2% in patients with VTE taking DOACs.
Importantly, DOACs were found to carry a statistically lower risk of major and fatal bleeding than VKAs. Patients taking DOACs have a relative risk of major bleeding of 0.72, compared with VKAs, and a RR of fatal bleeding of 0.53. Additionally, the case fatality rate for major bleeding episodes was 7.6% for DOACs versus 11.0% for warfarin, despite not having an available antidote for DOACs in these trials.3 Although there is an increased risk of bleeding from DOACs, the rates of major bleeding and of serious complications from bleeding are lower than with warfarin.
How long does the effect of a DOAC last?
A significant advantage of DOACs over VKAs in the setting of bleeding is their shorter half-lives, which range from a low estimate of 5 hours for rivaroxaban to a high estimate of 17 hours for dabigatran4-8 (Table 1). Given that it takes 4-5 half-lives for a drug to be functionally eliminated, coagulation typically normalizes in patients taking DOACs within 1-3 days, compared with 3-5 days for warfarin. All DOACs have significant renal clearance, and renal failure will prolong the duration of anticoagulation. For patients who are taking DOACs and present with bleeding, it is important to assess their renal function.
Are coagulation tests helpful when assessing the effect of DOACs?
Prothrombin time (PT/INR) and activated partial thromboplastin time (aPTT) should be measured in all patients presenting with significant bleeding, whether or not the patient is taking a DOAC. PT and aPTT are commonly elevated for patients taking direct thrombin inhibitors and Xa inhibitors. Although a prolonged PT and/or aPTT can be useful in determining if the anticoagulant effect from DOACs is still present, normal values of these tests do not rule out an anticoagulant effect in patients taking DOACs.9,10 Thrombin Time (TT) is a widely available test with quick results, and a normal value rules out the therapeutic effect of dabigatran. Finally, the anti–factor Xa assay is a sensitive test for Xa inhibitors, but requires calibration to the DOAC of interest in order to be reliable. Clinicians should consult with their institution’s laboratory prior to using an anti–factor Xa level to test the anticoagulant effect of a specific DOAC. Repeat coagulation testing may be useful in some clinical circumstances, especially if a patient has renal impairment.
Are there reversal agents for DOACs?
In October 2015, the FDA approved idarucizumab, a monoclonal antibody fragment that binds dabigatran with much greater affinity than thrombin, thus quickly reversing the effect of the direct thrombin inhibitor. FDA approval came in response to an interim analysis of an ongoing open-label trial, RE-VERSE AD.11 This study enrolled 90 adults with major bleeding or need for an emergency procedure taking dabigatran to receive idarucizumab (2.5 g in 50 mL rapid infusion dose given twice less than 15 minutes apart for a total of 5 g). Idarucizumab immediately reversed the effect of dabigatran on clotting tests in 88%-98% of the patients. For patients with major bleeding, the median time for bleeding cessation was 11.4 hours. One thrombotic event was reported within 72 hours of drug administration. Therefore, in patients taking dabigatran with an elevated TT, idarucizumab may be used if the bleeding is life threatening and refractory to initial supportive measures.
There are no FDA-approved antidotes for the factor Xa inhibitors. One promising agent is andexanet-alfa, an inactivated form of factor Xa that irreversibly binds Xa inhibitors. The ongoing, open-label ANNEXA-4 trial12 reported a decrease in anti–factor Xa activity of ~90% after bolus administration of the drug followed by 2-hour infusion in 67 patients with life-threatening bleeding, with clinical hemostasis achieved in 79% in patients by 12 hours. However, thrombotic events occurred in 18% of the patients at 1 month. Additional safety and efficacy data, along with plans for postmarket surveillance, will be needed prior to approval for clinical use.
Are there other options to obtain hemostasis?
Clotting factor products, specifically fresh frozen plasma (FFP) and prothrombin complex concentrates (PCCs), are often used to attempt to reverse anticoagulation from DOACs. While FFP alone has no evidence to support its use in reversing the effect of DOACs, PCCs might reverse anticoagulation for both Xa inhibitors and direct thrombin inhibitors.13 Some experts recommend unactivated PCC over activated PCC because of a theoretically increased thrombotic risk of activated PCC.14 For patients taking Xa inhibitors or dabigatran (if idarucizumab is unavailable) with life-threatening bleeding, PCC should be used in an attempt to reverse the bleeding.
Another strategy to promote hemostasis in bleeding patients taking DOACs is to use antifibrinolytics. Effective for control of bleeding in trauma and surgical patients, tranexamic acid has not been widely studied in nonsurgical bleeding, much less DOAC-related nonsurgical bleeding. A 2014 Cochrane review of a small number of trials suggested a possible mortality benefit from its use in upper GI bleeding, but the quality of included trials was poor.15 The ongoing HALT-IT trial, enrolling 8,000 patients with gastrointestinal bleeding, aims to clarify the mortality benefit of tranexamic acid.16 Despite effectively promoting hemostasis in many populations of bleeding patients, tranexamic acid carries no discernible thrombotic risk.17,18 By preventing clot degradation through a downstream mechanism at low cost and risk, antifibrinolytics are a practical adjunctive therapy to control major bleeding in patients on DOACs.
Can charcoal or dialysis reduce the systemic concentration of DOACs?
In addition to discontinuing the DOAC, both charcoal and dialysis can reduce the systemic concentration of DOACs. If the ingestion was recent, oral activated charcoal can reduce the systemic absorption of DOACs. To date there are no data on the efficacy of charcoal in bleeding patients taking DOACs. However, in two recent trials, administration of a single dose of charcoal in healthy patients led to significantly decreased area under concentration-time curves (AUC) when given at 6 and 8 hours after ingestion of a therapeutic dose of apixaban and rivaroxaban, respectively.19,20 While further studies are needed to confirm its clinical benefit, charcoal is recommended for major bleeding when given within 2 hours of ingestion of a DOAC and may be useful within 8 hours.
Unlike charcoal, which can be used for patients on Xa inhibitors or dabigatran, hemodialysis is only effective for reducing serum concentrations of dabigatran because of its low plasma protein binding (~35%). A review of 35 patients (10 with normal renal function) with severe bleeding showed significant reductions in coagulation tests (aPTT, PT, TT) and dabigatran levels after hemodialysis.21 For severe bleeding episodes particularly in patients with impaired renal function, providers should consider the use of continuous renal replacement therapy until clinical hemostasis is achieved.
What is the expert’s opinion?
We asked one of our hematologists with expertise in DOACs for his opinion on this topic. Most patients with DOAC-associated bleeding can be managed with supportive care because of the short half-life of these agents in patients with reasonably preserved renal function. The main scenario for escalating therapy to PCC or idarucizumab is life-threatening bleeding, such as intracranial hemorrhage and gastrointestinal hemorrhage with hemodynamic instability. The threshold for use of idarucizumab for patients taking dabigatran with bleeding should be lower than PCCs because there is better evidence for clinical benefit with less risk.
Developing reversal agents continues to be costly, requiring extensive preclinical work and clinical trials that are difficult to do. Assuming that reversal agents become more affordable in the longer term, and safety profiles are better established, clinicians may eventually have a lower threshold for their use in a wider variety of bleeding episodes. Lastly, adverse outcomes often occur, not during the acute bleeding episode, but several weeks later in patients whose providers delay restarting anticoagulation. Thus, it is important to resume anticoagulant therapy as soon as it is safe to do so.
Back to the case
Our patient was given a 50-g suspension of oral activated charcoal, along with two doses of 1 g intravenous tranexamic acid 8 hours apart. He was typed and crossed for blood, and ultimately received 1 unit of packed red blood cells before stabilizing without other measures. His colonoscopy subsequently revealed a diverticular bleed with a visible vessel that was coagulated. He was discharged 2 days later after remaining clinically stable after colonoscopy.
Bottom line
For the majority of bleeding patients on DOACs, supportive care with transfusions and local hemostatic interventions to control bleeding will likely be sufficient. Because of the short half-lives of DOACs, most patients do not require additional therapy (Table 2), and these patients actually have better outcomes from major bleeding episodes than patients taking VKAs. Antifibrinolytics should be a first-line prohemostatic therapy in major bleeding. Oral activated charcoal may be effective within 2-8 hours after ingestion for reduction of serum DOAC concentrations. Finally, in cases of life-threatening bleeding, idarucizumab can be used to reverse anticoagulation for patients taking dabigatran. When idarucizumab is unavailable, or for patients taking Xa inhibitors, PCC can be used.
Dr. Hagan is chief medical resident at the University of Washington Medical Center in Seattle. Dr. Albert is clinical instructor of medicine at UWMC. Dr. Garcia is professor of medicine and associate medical director of antithrombotic therapy at UWMC. Dr. Huang is an attending with the UWMC Medicine Consult Service and assistant clinical professor in the division of general internal medicine at UW.
Key Points
• The risk of major bleeding, and the case fatality rate of major bleeding, is significantly lower in patients taking DOACs versus VKAs
• For the majority of patients with bleeding on DOACs, withholding anticoagulation and supportive care is sufficient
• Idarucizumab is a novel and effective antidote to dabigatran, but should be reserved for patients with life-threatening bleeding
• Patients with DOAC-associated bleeding should be restarted on anticoagulation as soon as it is safe to do so
Additional Reading
Management of bleeding in patients receiving direct oral anticoagulants. UpToDate 2016.
How do I treat target-specific oral anticoagulant-associated bleeding? Blood 2014.
References
1. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest. 2016;149(2):315-52.
2. Chai-adisaksopha C, Crowther M, Isayama T, Lim W. The impact of bleeding complications in patients receiving target-specific oral anticoagulants: a systematic review and meta-analysis. Blood. 2014;124(15):2450-8.
3. Chai-adisaksopha C, Hillis C, Isayama T, Lim W, Iorio A, Crowther M. Mortality outcomes in patients receiving direct oral anticoagulants: a systematic review and meta-analysis of randomized controlled trials. J Thromb Haemost. 2015;13(11):2012-20.
4. Savaysa (edoxaban) [package insert]. Daiichi Sankyo, Inc, Tokyo, Japan; 2015. www.accessdata.fda.gov/drugsatfda_docs/label/2015/206316lbl.pdf. Accessed January 8th, 2016.
5. Xarelto (rivaroxaban) [package insert]. Janssen Pharmaceuticals, Inc. Titusville, NJ; 2011. www.accessdata.fda.gov/drugsatfda_docs/label/2011/202439s001lbl.pdf. Accessed January 8th, 2016.
6. Pradaxa (dabigatran) [package insert]. Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield, CT; 2011. www.accessdata.fda.gov/drugsatfda_docs/label/2011/022512s007lbl.pdf. Accessed January 8th, 2016.
7. Eliquis (apixaban) [package insert]. Bristol-Myers Squibb Company, Princeton, NJ; 2012. www.accessdata.fda.gov/drugsatfda_docs/label/2012/202155s000lbl.pdf. Accessed January 8th, 2016.
8. Scaglione F. New oral anticoagulants: comparative pharmacology with vitamin K antagonists. Clin Pharmacokinet. 2013;52(2):69-82.
9. Tripodi A. The laboratory and the direct oral anticoagulants. Blood.
2013;121(20):4032-5.
10. Samuelson BT, Cuker A, Siegal DM, Crowther M, Garcia DA. Laboratory Assessment of the Anticoagulant Activity of Direct Oral Anticoagulants (DOACs): A Systematic Review. Chest. 2016;
11. Pollack CV, Reilly PA, Eikelboom J, et al. Idarucizumab for Dabigatran Reversal. N Engl J Med. 2015;373(6):511-20.
12. Connolly SJ, Milling TJ, Eikelboom JW, et al. Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors. N Engl J Med. 2016.
13. Dickneite G, Hoffman M. Reversing the new oral anticoagulants with prothrombin complex concentrates (PCCs): what is the evidence?. Thromb Haemost. 2014;111(2):189-98.
14. Sørensen B, Spahn DR, Innerhofer P, Spannagl M, Rossaint R. Clinical review: Prothrombin complex concentrates--evaluation of safety and thrombogenicity. Crit Care. 2011;15(1):201.
15. Bennett C, Klingenberg S, Langholz E, Gluud L. Tranexamic acid for upper gastrointestinal bleeding. Cochrane Database of Systematic Reviews 2014, Issue 11. Art. No.: CD006640.
16. Roberts I, Coats T, Edwards P, et al. HALT-IT – tranexamic acid for the treatment of gastrointestinal bleeding: study protocol for a randomised controlled trial. Trials. 2014 Nov 19;15:450.
17. Dyba J, Chan F, Lau K, Chan A, Chan H. Tranexamic Acid is a Weak Provoking Factor for Thromboembolic Events: A Systematic Review of the Literature. Blood. 2013; 122(21): 3629.
18. Myles PS, Smith JA, Forbes A, et al. Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery. N Engl J Med. 2016; 376(2):136-148.
19. Wang X, Mondal S, Wang J, et al. Effect of Activated Charcoal on Apixaban Pharmacokinetics in Healthy Subjects. American Journal of Cardiovascular Drugs. 2014;14(2):147-154.
20. Ollier E, Hodin S, Lanoiselée J, et al. Effect of Activated Charcoal on Rivaroxaban Complex Absorption. Clin Pharmacokinet. 2016 Dec 2.
21. Chai-adisaksopha C, Hillis C, Lim W, Boonyawat K, Moffat K, Crowther M. Hemodialysis for the treatment of dabigatran-associated bleeding: a case report and systematic review. J Thromb Haemost. 2015;13(10):1790-8.
22. Schulman S, Kearon C. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005;3(4):692-4.
23. UW Anticoagulation Services. UW Medicine Pharmacy Services Web site. 2014. Available at https://depts.washington.edu/anticoag, Accessed March 8, 2017.
________________________________________________________________________
Table 1: Pharmacologic Profiles of Xa and Direct Thrombin Inhibitors4-8, 23
tmax t1/2, CrCl 50-80 t1/2 CrCl < 30 Dialyzable?
Apixaban 3-4 h 15 h 17 h No
Dabigatran 1-3 h 17 h 28 h Yes
Edoxaban 1-2 h 10-14 h no data No
Rivaroxaban 2-4 h 9 h 10 h No
tmax = time to peak serum concentration after ingestion, t1/2= serum half-life, CrCl= creatinine clearance in mL/min
*Average values assuming normal hepatic function. Aside from dabigatran, which has minimal hepatic clearance, all other DOACs can have prolonged half-lives in hepatic impairment.
Table 2: Management of Bleeding Patients Taking DOACs
Direct Thrombin Inhibitors (dabigatran)
Xa inhibitors (apixaban, edoxaban, rivaroxaban)Minor Bleeding
• Withhold DOAC
• Local hemostatic measures
Major Bleeding*
All of the above, AND
• Antifibrinolytic if bleeding persists
• Restore physiologic perfusion
• Charcoal if last dose within 2-8 hours
• Transfusion indications:
o Red blood cells: anemia
o Platelets: antiplatelet agents or thrombocytopenia
o Plasma: coagulopathy (dilution, DIC, liver failure), not for DOAC reversal
Life-threatening Bleeding**
All of the above, AND:
• Idarucizumab (confirm anticoagulant effect with thrombin time first)
• If idarucizumab is unavailable, use PCC
• Consider hemodialysis until hemostasis achieved, especially if patient in renal failure
All of the above, AND:
• Unactivated PCC (if available and calibrated to specific Xa inhibitor, confirm anticoagulant effect with anti-Xa level)
* Adapted from the International Society on Thrombosis and Hemostasis: bleeding with a fall in hemoglobin level ≥ 2 g/dL, OR bleeding leading to ≥ 2 units of PRBC transfused.21 Clinicians should perform risk stratification of bleeding episodes using vital signs, laboratory results, the area of bleeding, and patient comorbidities.
**Uncontrolled bleeding, OR symptomatic bleeding in a critical area or organ (such as intracranial, intraocular, intraspinal, retroperitoneal, pericardial, or intramuscular with compartment syndrome).
Case
A 72-year-old man with a history of nonvalvular atrial fibrillation (AF) and hypertension presents to the ER after an episode of hematochezia. He is prescribed dabigatran 150 mg twice daily for his AF and took his evening dose 2 hours prior to presentation. His initial exam reveals vital signs of BP 120/55, HR 105, RR 14 and bright red stool on rectal exam. His hemoglobin is 8.1 g/dL, down from 12.0 g/dL one month ago. He has normal renal function. How should you manage his gastrointestinal bleeding?
Background
Direct oral anticoagulants (DOACs) consist of two classes of drugs: oral factor Xa inhibitors (apixaban, edoxaban, and rivaroxaban) and direct thrombin inhibitors (dabigatran). They have gained substantial popularity since their commercial introduction in 2010, and are now Food and Drug Administration approved for the treatment of atrial fibrillation (AF) and venous thromboembolism (VTE) in noncancer patients. DOAC use will likely increase given favorable safety profiles, reliable pharmacokinetics, and recent guidelines recommending their use over vitamin K antagonists (VKAs) for treatment of VTE in noncancer patients.1
A primary concern about the routine use of DOACs has been the lack of commercially available direct reversal agents. Unlike warfarin, which has an effective rapid antidote, no direct reversal agent is available for Xa inhibitors, and only recently has there been FDA approval for idarucizumab, a direct thrombin inhibitor reversal drug. Therefore, clinicians are often left wondering how to manage bleeding episodes in patients receiving DOACs.
Literature review
What is the risk of bleeding for patients taking DOACs?
DOACs carry a low but significant risk of bleeding, including life-threatening bleeding. There is now robust data from over 100,000 patients in randomized clinical trials of nonvalvular AF and VTE comparing the risk of major and fatal bleeding between DOACs and VKAs.2 These trials reveal an annual major bleeding rate of 2%-4% in patients with AF and 1%-2% in patients with VTE taking DOACs.
Importantly, DOACs were found to carry a statistically lower risk of major and fatal bleeding than VKAs. Patients taking DOACs have a relative risk of major bleeding of 0.72, compared with VKAs, and a RR of fatal bleeding of 0.53. Additionally, the case fatality rate for major bleeding episodes was 7.6% for DOACs versus 11.0% for warfarin, despite not having an available antidote for DOACs in these trials.3 Although there is an increased risk of bleeding from DOACs, the rates of major bleeding and of serious complications from bleeding are lower than with warfarin.
How long does the effect of a DOAC last?
A significant advantage of DOACs over VKAs in the setting of bleeding is their shorter half-lives, which range from a low estimate of 5 hours for rivaroxaban to a high estimate of 17 hours for dabigatran4-8 (Table 1). Given that it takes 4-5 half-lives for a drug to be functionally eliminated, coagulation typically normalizes in patients taking DOACs within 1-3 days, compared with 3-5 days for warfarin. All DOACs have significant renal clearance, and renal failure will prolong the duration of anticoagulation. For patients who are taking DOACs and present with bleeding, it is important to assess their renal function.
Are coagulation tests helpful when assessing the effect of DOACs?
Prothrombin time (PT/INR) and activated partial thromboplastin time (aPTT) should be measured in all patients presenting with significant bleeding, whether or not the patient is taking a DOAC. PT and aPTT are commonly elevated for patients taking direct thrombin inhibitors and Xa inhibitors. Although a prolonged PT and/or aPTT can be useful in determining if the anticoagulant effect from DOACs is still present, normal values of these tests do not rule out an anticoagulant effect in patients taking DOACs.9,10 Thrombin Time (TT) is a widely available test with quick results, and a normal value rules out the therapeutic effect of dabigatran. Finally, the anti–factor Xa assay is a sensitive test for Xa inhibitors, but requires calibration to the DOAC of interest in order to be reliable. Clinicians should consult with their institution’s laboratory prior to using an anti–factor Xa level to test the anticoagulant effect of a specific DOAC. Repeat coagulation testing may be useful in some clinical circumstances, especially if a patient has renal impairment.
Are there reversal agents for DOACs?
In October 2015, the FDA approved idarucizumab, a monoclonal antibody fragment that binds dabigatran with much greater affinity than thrombin, thus quickly reversing the effect of the direct thrombin inhibitor. FDA approval came in response to an interim analysis of an ongoing open-label trial, RE-VERSE AD.11 This study enrolled 90 adults with major bleeding or need for an emergency procedure taking dabigatran to receive idarucizumab (2.5 g in 50 mL rapid infusion dose given twice less than 15 minutes apart for a total of 5 g). Idarucizumab immediately reversed the effect of dabigatran on clotting tests in 88%-98% of the patients. For patients with major bleeding, the median time for bleeding cessation was 11.4 hours. One thrombotic event was reported within 72 hours of drug administration. Therefore, in patients taking dabigatran with an elevated TT, idarucizumab may be used if the bleeding is life threatening and refractory to initial supportive measures.
There are no FDA-approved antidotes for the factor Xa inhibitors. One promising agent is andexanet-alfa, an inactivated form of factor Xa that irreversibly binds Xa inhibitors. The ongoing, open-label ANNEXA-4 trial12 reported a decrease in anti–factor Xa activity of ~90% after bolus administration of the drug followed by 2-hour infusion in 67 patients with life-threatening bleeding, with clinical hemostasis achieved in 79% in patients by 12 hours. However, thrombotic events occurred in 18% of the patients at 1 month. Additional safety and efficacy data, along with plans for postmarket surveillance, will be needed prior to approval for clinical use.
Are there other options to obtain hemostasis?
Clotting factor products, specifically fresh frozen plasma (FFP) and prothrombin complex concentrates (PCCs), are often used to attempt to reverse anticoagulation from DOACs. While FFP alone has no evidence to support its use in reversing the effect of DOACs, PCCs might reverse anticoagulation for both Xa inhibitors and direct thrombin inhibitors.13 Some experts recommend unactivated PCC over activated PCC because of a theoretically increased thrombotic risk of activated PCC.14 For patients taking Xa inhibitors or dabigatran (if idarucizumab is unavailable) with life-threatening bleeding, PCC should be used in an attempt to reverse the bleeding.
Another strategy to promote hemostasis in bleeding patients taking DOACs is to use antifibrinolytics. Effective for control of bleeding in trauma and surgical patients, tranexamic acid has not been widely studied in nonsurgical bleeding, much less DOAC-related nonsurgical bleeding. A 2014 Cochrane review of a small number of trials suggested a possible mortality benefit from its use in upper GI bleeding, but the quality of included trials was poor.15 The ongoing HALT-IT trial, enrolling 8,000 patients with gastrointestinal bleeding, aims to clarify the mortality benefit of tranexamic acid.16 Despite effectively promoting hemostasis in many populations of bleeding patients, tranexamic acid carries no discernible thrombotic risk.17,18 By preventing clot degradation through a downstream mechanism at low cost and risk, antifibrinolytics are a practical adjunctive therapy to control major bleeding in patients on DOACs.
Can charcoal or dialysis reduce the systemic concentration of DOACs?
In addition to discontinuing the DOAC, both charcoal and dialysis can reduce the systemic concentration of DOACs. If the ingestion was recent, oral activated charcoal can reduce the systemic absorption of DOACs. To date there are no data on the efficacy of charcoal in bleeding patients taking DOACs. However, in two recent trials, administration of a single dose of charcoal in healthy patients led to significantly decreased area under concentration-time curves (AUC) when given at 6 and 8 hours after ingestion of a therapeutic dose of apixaban and rivaroxaban, respectively.19,20 While further studies are needed to confirm its clinical benefit, charcoal is recommended for major bleeding when given within 2 hours of ingestion of a DOAC and may be useful within 8 hours.
Unlike charcoal, which can be used for patients on Xa inhibitors or dabigatran, hemodialysis is only effective for reducing serum concentrations of dabigatran because of its low plasma protein binding (~35%). A review of 35 patients (10 with normal renal function) with severe bleeding showed significant reductions in coagulation tests (aPTT, PT, TT) and dabigatran levels after hemodialysis.21 For severe bleeding episodes particularly in patients with impaired renal function, providers should consider the use of continuous renal replacement therapy until clinical hemostasis is achieved.
What is the expert’s opinion?
We asked one of our hematologists with expertise in DOACs for his opinion on this topic. Most patients with DOAC-associated bleeding can be managed with supportive care because of the short half-life of these agents in patients with reasonably preserved renal function. The main scenario for escalating therapy to PCC or idarucizumab is life-threatening bleeding, such as intracranial hemorrhage and gastrointestinal hemorrhage with hemodynamic instability. The threshold for use of idarucizumab for patients taking dabigatran with bleeding should be lower than PCCs because there is better evidence for clinical benefit with less risk.
Developing reversal agents continues to be costly, requiring extensive preclinical work and clinical trials that are difficult to do. Assuming that reversal agents become more affordable in the longer term, and safety profiles are better established, clinicians may eventually have a lower threshold for their use in a wider variety of bleeding episodes. Lastly, adverse outcomes often occur, not during the acute bleeding episode, but several weeks later in patients whose providers delay restarting anticoagulation. Thus, it is important to resume anticoagulant therapy as soon as it is safe to do so.
Back to the case
Our patient was given a 50-g suspension of oral activated charcoal, along with two doses of 1 g intravenous tranexamic acid 8 hours apart. He was typed and crossed for blood, and ultimately received 1 unit of packed red blood cells before stabilizing without other measures. His colonoscopy subsequently revealed a diverticular bleed with a visible vessel that was coagulated. He was discharged 2 days later after remaining clinically stable after colonoscopy.
Bottom line
For the majority of bleeding patients on DOACs, supportive care with transfusions and local hemostatic interventions to control bleeding will likely be sufficient. Because of the short half-lives of DOACs, most patients do not require additional therapy (Table 2), and these patients actually have better outcomes from major bleeding episodes than patients taking VKAs. Antifibrinolytics should be a first-line prohemostatic therapy in major bleeding. Oral activated charcoal may be effective within 2-8 hours after ingestion for reduction of serum DOAC concentrations. Finally, in cases of life-threatening bleeding, idarucizumab can be used to reverse anticoagulation for patients taking dabigatran. When idarucizumab is unavailable, or for patients taking Xa inhibitors, PCC can be used.
Dr. Hagan is chief medical resident at the University of Washington Medical Center in Seattle. Dr. Albert is clinical instructor of medicine at UWMC. Dr. Garcia is professor of medicine and associate medical director of antithrombotic therapy at UWMC. Dr. Huang is an attending with the UWMC Medicine Consult Service and assistant clinical professor in the division of general internal medicine at UW.
Key Points
• The risk of major bleeding, and the case fatality rate of major bleeding, is significantly lower in patients taking DOACs versus VKAs
• For the majority of patients with bleeding on DOACs, withholding anticoagulation and supportive care is sufficient
• Idarucizumab is a novel and effective antidote to dabigatran, but should be reserved for patients with life-threatening bleeding
• Patients with DOAC-associated bleeding should be restarted on anticoagulation as soon as it is safe to do so
Additional Reading
Management of bleeding in patients receiving direct oral anticoagulants. UpToDate 2016.
How do I treat target-specific oral anticoagulant-associated bleeding? Blood 2014.
References
1. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest. 2016;149(2):315-52.
2. Chai-adisaksopha C, Crowther M, Isayama T, Lim W. The impact of bleeding complications in patients receiving target-specific oral anticoagulants: a systematic review and meta-analysis. Blood. 2014;124(15):2450-8.
3. Chai-adisaksopha C, Hillis C, Isayama T, Lim W, Iorio A, Crowther M. Mortality outcomes in patients receiving direct oral anticoagulants: a systematic review and meta-analysis of randomized controlled trials. J Thromb Haemost. 2015;13(11):2012-20.
4. Savaysa (edoxaban) [package insert]. Daiichi Sankyo, Inc, Tokyo, Japan; 2015. www.accessdata.fda.gov/drugsatfda_docs/label/2015/206316lbl.pdf. Accessed January 8th, 2016.
5. Xarelto (rivaroxaban) [package insert]. Janssen Pharmaceuticals, Inc. Titusville, NJ; 2011. www.accessdata.fda.gov/drugsatfda_docs/label/2011/202439s001lbl.pdf. Accessed January 8th, 2016.
6. Pradaxa (dabigatran) [package insert]. Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield, CT; 2011. www.accessdata.fda.gov/drugsatfda_docs/label/2011/022512s007lbl.pdf. Accessed January 8th, 2016.
7. Eliquis (apixaban) [package insert]. Bristol-Myers Squibb Company, Princeton, NJ; 2012. www.accessdata.fda.gov/drugsatfda_docs/label/2012/202155s000lbl.pdf. Accessed January 8th, 2016.
8. Scaglione F. New oral anticoagulants: comparative pharmacology with vitamin K antagonists. Clin Pharmacokinet. 2013;52(2):69-82.
9. Tripodi A. The laboratory and the direct oral anticoagulants. Blood.
2013;121(20):4032-5.
10. Samuelson BT, Cuker A, Siegal DM, Crowther M, Garcia DA. Laboratory Assessment of the Anticoagulant Activity of Direct Oral Anticoagulants (DOACs): A Systematic Review. Chest. 2016;
11. Pollack CV, Reilly PA, Eikelboom J, et al. Idarucizumab for Dabigatran Reversal. N Engl J Med. 2015;373(6):511-20.
12. Connolly SJ, Milling TJ, Eikelboom JW, et al. Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors. N Engl J Med. 2016.
13. Dickneite G, Hoffman M. Reversing the new oral anticoagulants with prothrombin complex concentrates (PCCs): what is the evidence?. Thromb Haemost. 2014;111(2):189-98.
14. Sørensen B, Spahn DR, Innerhofer P, Spannagl M, Rossaint R. Clinical review: Prothrombin complex concentrates--evaluation of safety and thrombogenicity. Crit Care. 2011;15(1):201.
15. Bennett C, Klingenberg S, Langholz E, Gluud L. Tranexamic acid for upper gastrointestinal bleeding. Cochrane Database of Systematic Reviews 2014, Issue 11. Art. No.: CD006640.
16. Roberts I, Coats T, Edwards P, et al. HALT-IT – tranexamic acid for the treatment of gastrointestinal bleeding: study protocol for a randomised controlled trial. Trials. 2014 Nov 19;15:450.
17. Dyba J, Chan F, Lau K, Chan A, Chan H. Tranexamic Acid is a Weak Provoking Factor for Thromboembolic Events: A Systematic Review of the Literature. Blood. 2013; 122(21): 3629.
18. Myles PS, Smith JA, Forbes A, et al. Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery. N Engl J Med. 2016; 376(2):136-148.
19. Wang X, Mondal S, Wang J, et al. Effect of Activated Charcoal on Apixaban Pharmacokinetics in Healthy Subjects. American Journal of Cardiovascular Drugs. 2014;14(2):147-154.
20. Ollier E, Hodin S, Lanoiselée J, et al. Effect of Activated Charcoal on Rivaroxaban Complex Absorption. Clin Pharmacokinet. 2016 Dec 2.
21. Chai-adisaksopha C, Hillis C, Lim W, Boonyawat K, Moffat K, Crowther M. Hemodialysis for the treatment of dabigatran-associated bleeding: a case report and systematic review. J Thromb Haemost. 2015;13(10):1790-8.
22. Schulman S, Kearon C. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005;3(4):692-4.
23. UW Anticoagulation Services. UW Medicine Pharmacy Services Web site. 2014. Available at https://depts.washington.edu/anticoag, Accessed March 8, 2017.
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Table 1: Pharmacologic Profiles of Xa and Direct Thrombin Inhibitors4-8, 23
tmax t1/2, CrCl 50-80 t1/2 CrCl < 30 Dialyzable?
Apixaban 3-4 h 15 h 17 h No
Dabigatran 1-3 h 17 h 28 h Yes
Edoxaban 1-2 h 10-14 h no data No
Rivaroxaban 2-4 h 9 h 10 h No
tmax = time to peak serum concentration after ingestion, t1/2= serum half-life, CrCl= creatinine clearance in mL/min
*Average values assuming normal hepatic function. Aside from dabigatran, which has minimal hepatic clearance, all other DOACs can have prolonged half-lives in hepatic impairment.
Table 2: Management of Bleeding Patients Taking DOACs
Direct Thrombin Inhibitors (dabigatran)
Xa inhibitors (apixaban, edoxaban, rivaroxaban)Minor Bleeding
• Withhold DOAC
• Local hemostatic measures
Major Bleeding*
All of the above, AND
• Antifibrinolytic if bleeding persists
• Restore physiologic perfusion
• Charcoal if last dose within 2-8 hours
• Transfusion indications:
o Red blood cells: anemia
o Platelets: antiplatelet agents or thrombocytopenia
o Plasma: coagulopathy (dilution, DIC, liver failure), not for DOAC reversal
Life-threatening Bleeding**
All of the above, AND:
• Idarucizumab (confirm anticoagulant effect with thrombin time first)
• If idarucizumab is unavailable, use PCC
• Consider hemodialysis until hemostasis achieved, especially if patient in renal failure
All of the above, AND:
• Unactivated PCC (if available and calibrated to specific Xa inhibitor, confirm anticoagulant effect with anti-Xa level)
* Adapted from the International Society on Thrombosis and Hemostasis: bleeding with a fall in hemoglobin level ≥ 2 g/dL, OR bleeding leading to ≥ 2 units of PRBC transfused.21 Clinicians should perform risk stratification of bleeding episodes using vital signs, laboratory results, the area of bleeding, and patient comorbidities.
**Uncontrolled bleeding, OR symptomatic bleeding in a critical area or organ (such as intracranial, intraocular, intraspinal, retroperitoneal, pericardial, or intramuscular with compartment syndrome).
Statin use reduces death and decompensation in cirrhosis patients
Statin use in cirrhosis patients lowers the risk of death, Dr. Ulrich Bang and his associates reported in a retrospective case-cohort analysis.
After applying selection criteria, the investigators identified 5,417 patients with alcoholic cirrhosis from the Danish National Patient Registry based on the International Classification of Diseases, 10th revision, Danish National Prescription Registry based on the Anatomical Therapeutic Chemical, Danish Register of Causes of Death, and the Danish Civil Registration System from 1995 through 2014.
To conduct statistical analysis, the 5,417 were split into two groups – the first being an unmatched cohort. The unmatched cohort, which included all 5,417 patients, was not statistically balanced between statin vs. nonstatin users. Of the 5,417 patients, 744 were selected into a matched cohort using propensity scores (PS). This group was statistically balanced with one patient using statins being compared with two nonstatin users.
The unmatched group of 5,417 patients had 794 members (15%) who had used statins at least twice in a 30-day time period between first reported use and last reported use.
“In the unmatched cohort, we found mortality rates of 96 (86-106) per 1,000 [patient-years] for patients in therapy with statins and 121 (117-125) for the nonstatin patients and a [hazard ratio] of 0.66 (0.59-0.75) for statins vs. no statins,” the researchers wrote.
The PS-matched group’s “mortality rates were 88 (73-105) and 127 (114-142) for statin vs. nonstatin patients, respectively, and the HR was 0.57 (0.45-0.71)” (Aliment Pharmacol Ther. 2017 Oct;46[7]:673-80).
When analyzing decompensation, the rate of decompensation was 135 (114-160) per 1,000 person-years in those who had used statins for treatment. Among patients who had not undergone statin treatment, the rate was 361 (348-375) per 1,000 person-years. These results corresponded to an HR rate of 0.29 in an adjusted analysis. This varied from the PS-matched group, which experienced decompensation rates of 133 (104-170) for statin users and 234 (202-272) for nonstatin users.
In a subcohort analysis of 387 patients suffering from cirrhosis who had received consistent doses of statins, they had a reduced risk of death compared to an unmatched group of 4,975 patients who had not used statins. Patients receiving consistent doses of statins were said to be in a “stable” state. Ultimately, it was found for each 25% increase in stable state statin dosing, the risk of death decreased by 16%.
“The use of statins was associated with a reduced risk of decompensation and death in patients with alcoholic cirrhosis and the association between use of statins and death was more pronounced in patients with cirrhosis compared with noncirrhotic controls,” the investigators noted. “No convincing dose-response association was found but patients with a more constant exposure to statins may benefit more from the treatment.”
One coauthor had previously served as an adviser to Ferring Pharmaceuticals and as a speaker for Norgine Danmark. There were no other financial disclosures to report.
Statin use in cirrhosis patients lowers the risk of death, Dr. Ulrich Bang and his associates reported in a retrospective case-cohort analysis.
After applying selection criteria, the investigators identified 5,417 patients with alcoholic cirrhosis from the Danish National Patient Registry based on the International Classification of Diseases, 10th revision, Danish National Prescription Registry based on the Anatomical Therapeutic Chemical, Danish Register of Causes of Death, and the Danish Civil Registration System from 1995 through 2014.
To conduct statistical analysis, the 5,417 were split into two groups – the first being an unmatched cohort. The unmatched cohort, which included all 5,417 patients, was not statistically balanced between statin vs. nonstatin users. Of the 5,417 patients, 744 were selected into a matched cohort using propensity scores (PS). This group was statistically balanced with one patient using statins being compared with two nonstatin users.
The unmatched group of 5,417 patients had 794 members (15%) who had used statins at least twice in a 30-day time period between first reported use and last reported use.
“In the unmatched cohort, we found mortality rates of 96 (86-106) per 1,000 [patient-years] for patients in therapy with statins and 121 (117-125) for the nonstatin patients and a [hazard ratio] of 0.66 (0.59-0.75) for statins vs. no statins,” the researchers wrote.
The PS-matched group’s “mortality rates were 88 (73-105) and 127 (114-142) for statin vs. nonstatin patients, respectively, and the HR was 0.57 (0.45-0.71)” (Aliment Pharmacol Ther. 2017 Oct;46[7]:673-80).
When analyzing decompensation, the rate of decompensation was 135 (114-160) per 1,000 person-years in those who had used statins for treatment. Among patients who had not undergone statin treatment, the rate was 361 (348-375) per 1,000 person-years. These results corresponded to an HR rate of 0.29 in an adjusted analysis. This varied from the PS-matched group, which experienced decompensation rates of 133 (104-170) for statin users and 234 (202-272) for nonstatin users.
In a subcohort analysis of 387 patients suffering from cirrhosis who had received consistent doses of statins, they had a reduced risk of death compared to an unmatched group of 4,975 patients who had not used statins. Patients receiving consistent doses of statins were said to be in a “stable” state. Ultimately, it was found for each 25% increase in stable state statin dosing, the risk of death decreased by 16%.
“The use of statins was associated with a reduced risk of decompensation and death in patients with alcoholic cirrhosis and the association between use of statins and death was more pronounced in patients with cirrhosis compared with noncirrhotic controls,” the investigators noted. “No convincing dose-response association was found but patients with a more constant exposure to statins may benefit more from the treatment.”
One coauthor had previously served as an adviser to Ferring Pharmaceuticals and as a speaker for Norgine Danmark. There were no other financial disclosures to report.
Statin use in cirrhosis patients lowers the risk of death, Dr. Ulrich Bang and his associates reported in a retrospective case-cohort analysis.
After applying selection criteria, the investigators identified 5,417 patients with alcoholic cirrhosis from the Danish National Patient Registry based on the International Classification of Diseases, 10th revision, Danish National Prescription Registry based on the Anatomical Therapeutic Chemical, Danish Register of Causes of Death, and the Danish Civil Registration System from 1995 through 2014.
To conduct statistical analysis, the 5,417 were split into two groups – the first being an unmatched cohort. The unmatched cohort, which included all 5,417 patients, was not statistically balanced between statin vs. nonstatin users. Of the 5,417 patients, 744 were selected into a matched cohort using propensity scores (PS). This group was statistically balanced with one patient using statins being compared with two nonstatin users.
The unmatched group of 5,417 patients had 794 members (15%) who had used statins at least twice in a 30-day time period between first reported use and last reported use.
“In the unmatched cohort, we found mortality rates of 96 (86-106) per 1,000 [patient-years] for patients in therapy with statins and 121 (117-125) for the nonstatin patients and a [hazard ratio] of 0.66 (0.59-0.75) for statins vs. no statins,” the researchers wrote.
The PS-matched group’s “mortality rates were 88 (73-105) and 127 (114-142) for statin vs. nonstatin patients, respectively, and the HR was 0.57 (0.45-0.71)” (Aliment Pharmacol Ther. 2017 Oct;46[7]:673-80).
When analyzing decompensation, the rate of decompensation was 135 (114-160) per 1,000 person-years in those who had used statins for treatment. Among patients who had not undergone statin treatment, the rate was 361 (348-375) per 1,000 person-years. These results corresponded to an HR rate of 0.29 in an adjusted analysis. This varied from the PS-matched group, which experienced decompensation rates of 133 (104-170) for statin users and 234 (202-272) for nonstatin users.
In a subcohort analysis of 387 patients suffering from cirrhosis who had received consistent doses of statins, they had a reduced risk of death compared to an unmatched group of 4,975 patients who had not used statins. Patients receiving consistent doses of statins were said to be in a “stable” state. Ultimately, it was found for each 25% increase in stable state statin dosing, the risk of death decreased by 16%.
“The use of statins was associated with a reduced risk of decompensation and death in patients with alcoholic cirrhosis and the association between use of statins and death was more pronounced in patients with cirrhosis compared with noncirrhotic controls,” the investigators noted. “No convincing dose-response association was found but patients with a more constant exposure to statins may benefit more from the treatment.”
One coauthor had previously served as an adviser to Ferring Pharmaceuticals and as a speaker for Norgine Danmark. There were no other financial disclosures to report.
FROM ALIMENTARY PHARMACOLOGY & THERAPEUTICS
Key clinical point:
Major finding: As likelihood of stable state increases by 25% with statin dose, death risk decreases by 16%.
Data source: A retrospective case-cohort analysis of information obtained from registrants in the Danish National Patient Registry based on International Classification of Diseases, 10th revision (ICD-10), Danish National Prescription Registry based on the Anatomical Therapeutic Chemical (ATC), Danish Register of Causes of Death, and the Danish Civil Registration System between the years 1995 and 2014.
Disclosures: One coauthor had previously served as an adviser to Ferring Pharmaceuticals and as a speaker for Norgine Danmark. There were no other financial disclosures to report.