The Food and Drug Administration has approved emicizumab-kxwh (Hemlibra) for the prevention or reduction of bleeding episodes for adult and pediatric patients with hemophilia A with Factor VIII inhibitors.

[email protected]

The Food and Drug Administration has approved emicizumab-kxwh (Hemlibra) for the prevention or reduction of bleeding episodes for adult and pediatric patients with hemophilia A with Factor VIII inhibitors.

[email protected]

The Food and Drug Administration has approved emicizumab-kxwh (Hemlibra) for the prevention or reduction of bleeding episodes for adult and pediatric patients with hemophilia A with Factor VIII inhibitors.

[email protected]

PARIS – Huge longitudinal Scandinavian population registries constitute a unique data source that, in recent years, has provided new insights into attention-deficit/hyperactivity disorder and its associated risks of suicidal behavior, accidents, and early mortality, Henrik Larsson, PhD, said at the annual congress of the European College of Neuropsychopharmacology.

“Randomized, controlled trials have provided little information about real-world effectiveness of ADHD medications, such as their potential effects on adverse health outcomes,” said Dr. Larsson of the Karolinska Institute in Stockholm.

Suicidality

Dr. Larsson was senior author of a Swedish national registry study that identified 51,707 patients with ADHD matched by sex and birth year to 258,535 controls. The ADHD patients had significantly higher rates of both attempted and completed suicide.

After adjustment for socioeconomic status, these individuals were at 8.46-fold increased risk for attempted suicide. However, after further adjustment for comorbid psychiatric disorders, this dropped substantially to a 3.62-fold increased risk.

The same pattern pertained to completed suicide: The risk after adjustment for socioeconomic status was increased 12.3-fold in individuals with ADHD, compared with controls, but the risk dropped to 5.91-fold after further adjustment for comorbid psychiatric disorders (JAMA Psychiatry. 2014 Aug;71[8]:958-64).

The clinical take home point: “Detection and treatment of comorbid conditions probably will help reduce suicidal behavior in ADHD,” Dr. Larsson said.

This study also showed that increased familial risk also is a key factor in the increased risk of suicidal behavior in the ADHD population. Parents of individuals with ADHD were at 2.42-fold increased risk of attempted suicide, compared with controls, and full siblings were at 2.28-fold increased risk. In contrast, the risk in half-siblings, while significantly greater than in controls, was lower than in the genetically closer first-degree relatives: Maternal half-siblings were at 1.57-fold increased risk, and paternal half-siblings were at 1.57-fold greater risk. Cousins were at 1.39-fold increased risk.

The same held true for completed suicide risk. And the familial associations remained significant even after excluding relatives with ADHD.

“Regarding the shared familial factors, I’m tempted to hypothesize that this might involve pleiotropic effects reflecting genetic variants associated with impulsivity,” said Dr. Larsson. To further understand the biological mechanisms underlying ADHD and associated adverse health outcomes requires multiple disciplines to work together. For such work, Dr. Larsson collaborates with international colleagues in several consortia.
 

ADHD medications and suicidality

Concerns regarding this question were raised by a meta-analysis based on clinical trials data that suggested patients’ increased suicidality might be caused by the effects of ADHD medications. But the meta-analysis was seriously flawed by what epidemiologists call confounding by indication, which is the potential for bias to be introduced when a group of patients on medication is compared with another group off medication. The confounding results from the fact that ADHD patients on medication are different from those who aren’t: They are likely to be more symptomatic and have more comorbidities.

To bypass the confounding issue, Dr. Larsson and his coinvestigators turned to the Swedish registries and identified 37,936 patients with ADHD with a total of 7,019 suicide-related events during nearly 151,000 person-years of follow-up. When they compared patients on drug treatment with those who were not, they found – as in the other investigators’ meta-analysis – that drug treatment was associated with a statistically significant 1.31-fold increased risk of suicide-related events. However, when they performed a more appropriate between-individual analysis, Dr. Larsson and his colleagues found that, when patients with ADHD were using stimulant medications, they had a significant 19% lower risk of suicide-related events than when they were off medication. While on nonstimulant ADHD medications, their suicidality risk was no different from when off medication (BMJ. 2014 Jun 18;348:g3769. doi: 10.1136/bmj.g3769).
 

ADHD and early mortality risk

Prior studies have established that ADHD is associated with a proclivity to engage in risk-taking behaviors, including substance abuse, criminality, risky sexual behavior, and accidents, which are themselves associated with early mortality.

Sure enough, when Danish investigators turned to their national registries, identified 32,061 individuals with ADHD born during 1981-2011, and followed them through 2013, they found that, during nearly 25 million person-years of follow-up, the mortality rate was 5.85 deaths per 10,000 person-years in individuals with ADHD, compared with 2.21 deaths per 10,000 person-years in controls, resulting in a fully adjusted mortality rate ratio of 2.07. The rate ratio was 1.86 for ADHD patients under age 6 years, 1.58 in those aged 6-17 years, and 4.25 for patients aged 18 years and older (Lancet. 2015 May 30;385[9983]:2190-6).

Accidents were the most common cause of death. Could ADHD medications modify this risk of fatal accidents?
 

Serious motor vehicle accidents

Dr. Larsson and his coinvestigators used registry data to follow 17,408 Swedish adults with ADHD for serious transport accidents involving a trip to the emergency room or death during 2006-2009. The risk was increased by an adjusted 1.47-fold in men with ADHD and by 1.45-fold in women with the disorder. However, in the within-individual analysis, men were 58% less likely to have a serious transport accident when they were on ADHD medication than when off medication. There was no statistically significant effect of ADHD medications on the risk in women with ADHD.

The investigators estimated that 41%-49% of transport accidents in men with ADHD could have been avoided had they been on drug therapy continuously throughout the follow-up period (JAMA Psychiatry. 2014 Mar;71[3]:319-25).

Similar results – that is, data showing that being on ADHD medication reduces the elevated risk of serious accidents – have been reported in four other independent studies conducted in Denmark, Germany, Hong Kong, and most recently in a U.S. analysis by Dr. Larsson and coinvestigators of more than 2.3 million patients with ADHD in a U.S. commercial health insurance claims database (JAMA Psychiatry. 2017 Jun 1;74[6]:597-603).

These findings collectively highlight the public health importance of diagnosing and treating ADHD.

But Dr. Larsson wanted his audience to take home another key lesson: “ADHD is a disorder that can be associated with serious outcomes, including suicide and accidents. It’s nevertheless important to remember that the absolute risks here are very low for any of these outcomes, so the majority of individuals with ADHD will never suffer from any of these outcomes. It’s important to keep that in mind.”

Dr. Larsson’s research is funded by the Swedish Research Council, the National Institute of Mental Health, FORTE, Horizon 2020, and Shire.

[email protected]

PARIS – Huge longitudinal Scandinavian population registries constitute a unique data source that, in recent years, has provided new insights into attention-deficit/hyperactivity disorder and its associated risks of suicidal behavior, accidents, and early mortality, Henrik Larsson, PhD, said at the annual congress of the European College of Neuropsychopharmacology.

“Randomized, controlled trials have provided little information about real-world effectiveness of ADHD medications, such as their potential effects on adverse health outcomes,” said Dr. Larsson of the Karolinska Institute in Stockholm.

Suicidality

Dr. Larsson was senior author of a Swedish national registry study that identified 51,707 patients with ADHD matched by sex and birth year to 258,535 controls. The ADHD patients had significantly higher rates of both attempted and completed suicide.

After adjustment for socioeconomic status, these individuals were at 8.46-fold increased risk for attempted suicide. However, after further adjustment for comorbid psychiatric disorders, this dropped substantially to a 3.62-fold increased risk.

The same pattern pertained to completed suicide: The risk after adjustment for socioeconomic status was increased 12.3-fold in individuals with ADHD, compared with controls, but the risk dropped to 5.91-fold after further adjustment for comorbid psychiatric disorders (JAMA Psychiatry. 2014 Aug;71[8]:958-64).

The clinical take home point: “Detection and treatment of comorbid conditions probably will help reduce suicidal behavior in ADHD,” Dr. Larsson said.

This study also showed that increased familial risk also is a key factor in the increased risk of suicidal behavior in the ADHD population. Parents of individuals with ADHD were at 2.42-fold increased risk of attempted suicide, compared with controls, and full siblings were at 2.28-fold increased risk. In contrast, the risk in half-siblings, while significantly greater than in controls, was lower than in the genetically closer first-degree relatives: Maternal half-siblings were at 1.57-fold increased risk, and paternal half-siblings were at 1.57-fold greater risk. Cousins were at 1.39-fold increased risk.

The same held true for completed suicide risk. And the familial associations remained significant even after excluding relatives with ADHD.

“Regarding the shared familial factors, I’m tempted to hypothesize that this might involve pleiotropic effects reflecting genetic variants associated with impulsivity,” said Dr. Larsson. To further understand the biological mechanisms underlying ADHD and associated adverse health outcomes requires multiple disciplines to work together. For such work, Dr. Larsson collaborates with international colleagues in several consortia.
 

ADHD medications and suicidality

Concerns regarding this question were raised by a meta-analysis based on clinical trials data that suggested patients’ increased suicidality might be caused by the effects of ADHD medications. But the meta-analysis was seriously flawed by what epidemiologists call confounding by indication, which is the potential for bias to be introduced when a group of patients on medication is compared with another group off medication. The confounding results from the fact that ADHD patients on medication are different from those who aren’t: They are likely to be more symptomatic and have more comorbidities.

To bypass the confounding issue, Dr. Larsson and his coinvestigators turned to the Swedish registries and identified 37,936 patients with ADHD with a total of 7,019 suicide-related events during nearly 151,000 person-years of follow-up. When they compared patients on drug treatment with those who were not, they found – as in the other investigators’ meta-analysis – that drug treatment was associated with a statistically significant 1.31-fold increased risk of suicide-related events. However, when they performed a more appropriate between-individual analysis, Dr. Larsson and his colleagues found that, when patients with ADHD were using stimulant medications, they had a significant 19% lower risk of suicide-related events than when they were off medication. While on nonstimulant ADHD medications, their suicidality risk was no different from when off medication (BMJ. 2014 Jun 18;348:g3769. doi: 10.1136/bmj.g3769).
 

ADHD and early mortality risk

Prior studies have established that ADHD is associated with a proclivity to engage in risk-taking behaviors, including substance abuse, criminality, risky sexual behavior, and accidents, which are themselves associated with early mortality.

Sure enough, when Danish investigators turned to their national registries, identified 32,061 individuals with ADHD born during 1981-2011, and followed them through 2013, they found that, during nearly 25 million person-years of follow-up, the mortality rate was 5.85 deaths per 10,000 person-years in individuals with ADHD, compared with 2.21 deaths per 10,000 person-years in controls, resulting in a fully adjusted mortality rate ratio of 2.07. The rate ratio was 1.86 for ADHD patients under age 6 years, 1.58 in those aged 6-17 years, and 4.25 for patients aged 18 years and older (Lancet. 2015 May 30;385[9983]:2190-6).

Accidents were the most common cause of death. Could ADHD medications modify this risk of fatal accidents?
 

Serious motor vehicle accidents

Dr. Larsson and his coinvestigators used registry data to follow 17,408 Swedish adults with ADHD for serious transport accidents involving a trip to the emergency room or death during 2006-2009. The risk was increased by an adjusted 1.47-fold in men with ADHD and by 1.45-fold in women with the disorder. However, in the within-individual analysis, men were 58% less likely to have a serious transport accident when they were on ADHD medication than when off medication. There was no statistically significant effect of ADHD medications on the risk in women with ADHD.

The investigators estimated that 41%-49% of transport accidents in men with ADHD could have been avoided had they been on drug therapy continuously throughout the follow-up period (JAMA Psychiatry. 2014 Mar;71[3]:319-25).

Similar results – that is, data showing that being on ADHD medication reduces the elevated risk of serious accidents – have been reported in four other independent studies conducted in Denmark, Germany, Hong Kong, and most recently in a U.S. analysis by Dr. Larsson and coinvestigators of more than 2.3 million patients with ADHD in a U.S. commercial health insurance claims database (JAMA Psychiatry. 2017 Jun 1;74[6]:597-603).

These findings collectively highlight the public health importance of diagnosing and treating ADHD.

But Dr. Larsson wanted his audience to take home another key lesson: “ADHD is a disorder that can be associated with serious outcomes, including suicide and accidents. It’s nevertheless important to remember that the absolute risks here are very low for any of these outcomes, so the majority of individuals with ADHD will never suffer from any of these outcomes. It’s important to keep that in mind.”

Dr. Larsson’s research is funded by the Swedish Research Council, the National Institute of Mental Health, FORTE, Horizon 2020, and Shire.

[email protected]

PARIS – Huge longitudinal Scandinavian population registries constitute a unique data source that, in recent years, has provided new insights into attention-deficit/hyperactivity disorder and its associated risks of suicidal behavior, accidents, and early mortality, Henrik Larsson, PhD, said at the annual congress of the European College of Neuropsychopharmacology.

“Randomized, controlled trials have provided little information about real-world effectiveness of ADHD medications, such as their potential effects on adverse health outcomes,” said Dr. Larsson of the Karolinska Institute in Stockholm.

Suicidality

Dr. Larsson was senior author of a Swedish national registry study that identified 51,707 patients with ADHD matched by sex and birth year to 258,535 controls. The ADHD patients had significantly higher rates of both attempted and completed suicide.

After adjustment for socioeconomic status, these individuals were at 8.46-fold increased risk for attempted suicide. However, after further adjustment for comorbid psychiatric disorders, this dropped substantially to a 3.62-fold increased risk.

The same pattern pertained to completed suicide: The risk after adjustment for socioeconomic status was increased 12.3-fold in individuals with ADHD, compared with controls, but the risk dropped to 5.91-fold after further adjustment for comorbid psychiatric disorders (JAMA Psychiatry. 2014 Aug;71[8]:958-64).

The clinical take home point: “Detection and treatment of comorbid conditions probably will help reduce suicidal behavior in ADHD,” Dr. Larsson said.

This study also showed that increased familial risk also is a key factor in the increased risk of suicidal behavior in the ADHD population. Parents of individuals with ADHD were at 2.42-fold increased risk of attempted suicide, compared with controls, and full siblings were at 2.28-fold increased risk. In contrast, the risk in half-siblings, while significantly greater than in controls, was lower than in the genetically closer first-degree relatives: Maternal half-siblings were at 1.57-fold increased risk, and paternal half-siblings were at 1.57-fold greater risk. Cousins were at 1.39-fold increased risk.

The same held true for completed suicide risk. And the familial associations remained significant even after excluding relatives with ADHD.

“Regarding the shared familial factors, I’m tempted to hypothesize that this might involve pleiotropic effects reflecting genetic variants associated with impulsivity,” said Dr. Larsson. To further understand the biological mechanisms underlying ADHD and associated adverse health outcomes requires multiple disciplines to work together. For such work, Dr. Larsson collaborates with international colleagues in several consortia.
 

ADHD medications and suicidality

Concerns regarding this question were raised by a meta-analysis based on clinical trials data that suggested patients’ increased suicidality might be caused by the effects of ADHD medications. But the meta-analysis was seriously flawed by what epidemiologists call confounding by indication, which is the potential for bias to be introduced when a group of patients on medication is compared with another group off medication. The confounding results from the fact that ADHD patients on medication are different from those who aren’t: They are likely to be more symptomatic and have more comorbidities.

To bypass the confounding issue, Dr. Larsson and his coinvestigators turned to the Swedish registries and identified 37,936 patients with ADHD with a total of 7,019 suicide-related events during nearly 151,000 person-years of follow-up. When they compared patients on drug treatment with those who were not, they found – as in the other investigators’ meta-analysis – that drug treatment was associated with a statistically significant 1.31-fold increased risk of suicide-related events. However, when they performed a more appropriate between-individual analysis, Dr. Larsson and his colleagues found that, when patients with ADHD were using stimulant medications, they had a significant 19% lower risk of suicide-related events than when they were off medication. While on nonstimulant ADHD medications, their suicidality risk was no different from when off medication (BMJ. 2014 Jun 18;348:g3769. doi: 10.1136/bmj.g3769).
 

ADHD and early mortality risk

Prior studies have established that ADHD is associated with a proclivity to engage in risk-taking behaviors, including substance abuse, criminality, risky sexual behavior, and accidents, which are themselves associated with early mortality.

Sure enough, when Danish investigators turned to their national registries, identified 32,061 individuals with ADHD born during 1981-2011, and followed them through 2013, they found that, during nearly 25 million person-years of follow-up, the mortality rate was 5.85 deaths per 10,000 person-years in individuals with ADHD, compared with 2.21 deaths per 10,000 person-years in controls, resulting in a fully adjusted mortality rate ratio of 2.07. The rate ratio was 1.86 for ADHD patients under age 6 years, 1.58 in those aged 6-17 years, and 4.25 for patients aged 18 years and older (Lancet. 2015 May 30;385[9983]:2190-6).

Accidents were the most common cause of death. Could ADHD medications modify this risk of fatal accidents?
 

Serious motor vehicle accidents

Dr. Larsson and his coinvestigators used registry data to follow 17,408 Swedish adults with ADHD for serious transport accidents involving a trip to the emergency room or death during 2006-2009. The risk was increased by an adjusted 1.47-fold in men with ADHD and by 1.45-fold in women with the disorder. However, in the within-individual analysis, men were 58% less likely to have a serious transport accident when they were on ADHD medication than when off medication. There was no statistically significant effect of ADHD medications on the risk in women with ADHD.

The investigators estimated that 41%-49% of transport accidents in men with ADHD could have been avoided had they been on drug therapy continuously throughout the follow-up period (JAMA Psychiatry. 2014 Mar;71[3]:319-25).

Similar results – that is, data showing that being on ADHD medication reduces the elevated risk of serious accidents – have been reported in four other independent studies conducted in Denmark, Germany, Hong Kong, and most recently in a U.S. analysis by Dr. Larsson and coinvestigators of more than 2.3 million patients with ADHD in a U.S. commercial health insurance claims database (JAMA Psychiatry. 2017 Jun 1;74[6]:597-603).

These findings collectively highlight the public health importance of diagnosing and treating ADHD.

But Dr. Larsson wanted his audience to take home another key lesson: “ADHD is a disorder that can be associated with serious outcomes, including suicide and accidents. It’s nevertheless important to remember that the absolute risks here are very low for any of these outcomes, so the majority of individuals with ADHD will never suffer from any of these outcomes. It’s important to keep that in mind.”

Dr. Larsson’s research is funded by the Swedish Research Council, the National Institute of Mental Health, FORTE, Horizon 2020, and Shire.

[email protected]

Establishing a pediatric flu shot program increases vaccine compliance, and makes for happy patients and parents. It won’t hurt your bottom line either and actually will help it. A flu shot program potentially can be run by a licensed practical nurse, registered nurse, physician’s assistant, or pediatric nurse practitioner, depending on your state’s law regarding vaccine administration by other than a physician, thus freeing up the physician to see well-child and sick-call patients.

It’s easy to set up a flu shot program and run it. Start preparing in June, preceding the upcoming flu season. Designate several Saturdays and or Sundays in September, October, November, December, and January as flu shot Saturdays and/or Sundays. And if Columbus day falls on a weekday, consider adding Columbus Day to your program dates as the kids often are off from school that day (check the local school calendar).

Yarinca/istockphoto

Mr. Berman has been providing practice management services to physicians and other medical providers since 1983. He is the CEO of a pediatrics practice with locations in Staten Island and Brooklyn, N.Y. He holds a faculty appointment at State University of New York, Brooklyn, as a lecturer for the department of family medicine’s residency training program. He has no disclosures to report. Email him at [email protected].

Establishing a pediatric flu shot program increases vaccine compliance, and makes for happy patients and parents. It won’t hurt your bottom line either and actually will help it. A flu shot program potentially can be run by a licensed practical nurse, registered nurse, physician’s assistant, or pediatric nurse practitioner, depending on your state’s law regarding vaccine administration by other than a physician, thus freeing up the physician to see well-child and sick-call patients.

It’s easy to set up a flu shot program and run it. Start preparing in June, preceding the upcoming flu season. Designate several Saturdays and or Sundays in September, October, November, December, and January as flu shot Saturdays and/or Sundays. And if Columbus day falls on a weekday, consider adding Columbus Day to your program dates as the kids often are off from school that day (check the local school calendar).

Yarinca/istockphoto

Mr. Berman has been providing practice management services to physicians and other medical providers since 1983. He is the CEO of a pediatrics practice with locations in Staten Island and Brooklyn, N.Y. He holds a faculty appointment at State University of New York, Brooklyn, as a lecturer for the department of family medicine’s residency training program. He has no disclosures to report. Email him at [email protected].

Establishing a pediatric flu shot program increases vaccine compliance, and makes for happy patients and parents. It won’t hurt your bottom line either and actually will help it. A flu shot program potentially can be run by a licensed practical nurse, registered nurse, physician’s assistant, or pediatric nurse practitioner, depending on your state’s law regarding vaccine administration by other than a physician, thus freeing up the physician to see well-child and sick-call patients.

It’s easy to set up a flu shot program and run it. Start preparing in June, preceding the upcoming flu season. Designate several Saturdays and or Sundays in September, October, November, December, and January as flu shot Saturdays and/or Sundays. And if Columbus day falls on a weekday, consider adding Columbus Day to your program dates as the kids often are off from school that day (check the local school calendar).

Yarinca/istockphoto

Mr. Berman has been providing practice management services to physicians and other medical providers since 1983. He is the CEO of a pediatrics practice with locations in Staten Island and Brooklyn, N.Y. He holds a faculty appointment at State University of New York, Brooklyn, as a lecturer for the department of family medicine’s residency training program. He has no disclosures to report. Email him at [email protected].

Children’s Research Hospital

Researchers say they have uncovered a target to overcome drug resistance in acute myeloid leukemia (AML).

The team discovered how a linkage between 2 proteins enables AML cells to resist chemotherapy and showed that disrupting the linkage could render the cells vulnerable to treatment.

The researchers believe their discovery could lead to drugs to enhance chemotherapy in patients with AML and other cancers.

John Schuetz, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues described this research in Nature Communications.

The team launched their experiments based on previous findings that a protein called ABCC4 was greatly elevated in aggressive cases of AML.

Dr Schuetz and his colleagues searched for other proteins that might interact with ABCC4 and enable its function. The team’s screening of candidate proteins yielded one, MPP1, which was also greatly increased in AML.

The researchers found the 2 proteins are connected, and the connection enables cells to assume the characteristics of highly proliferative leukemia cells.

These experiments involved genetically altering hematopoietic progenitor cells to have high MPP1 and ABCC4 levels. The cells were grown in culture and then replated to see if they would continue to grow, as such self-renewal is a hallmark of leukemia cells.

The researchers found that serial regrowth depended on the cells having high levels of both ABCC4 and MPP1.

“Typically, if you take normal progenitors and you replate, you could do that one time, maybe twice,” Dr Schuetz said. “But our big surprise was that overexpressing MPP1—analogous to what you would see in leukemia—allows those progenitors to self-renew, to be replated over and over, to form new colonies.”

The experiments also revealed that MPP1 and ABCC4 functioned at the cell membrane, where they could play a role in the machinery that would rid the leukemia cells of chemotherapy drugs.

“When we disrupted their interaction, ABCC4 moved off the membrane and the cells became more sensitive to drugs used in AML—drugs that are pumped out of the cell by ABCC4,” Dr Schuetz said.

By screening thousands of compounds, the researchers identified some that could disrupt the ABCC4-MPP1 connection. One, called Antimycin-A, reversed drug resistance in AML cell lines and in cells from AML patients.

Antimycin-A is too toxic to be used in chemotherapy, but the researchers believe identification of the compound should aid the search for other, less-toxic drugs to disrupt the ABCC4-MPP1 interaction.

The team’s findings could also enable clinicians to identify AML patients with high levels of ABCC4 and MPP1. In such patients, drugs that disrupt ABCC4-MPP1 might enhance the effectiveness of standard chemotherapy, Dr Schuetz said.

He also noted that other cancers, including breast and colon cancer and medulloblastoma, show high levels of both ABCC4 and MPP1. Chemotherapy for those cancers might also be enhanced by drugs that disrupt ABCC4-MPP1.

Children’s Research Hospital

Researchers say they have uncovered a target to overcome drug resistance in acute myeloid leukemia (AML).

The team discovered how a linkage between 2 proteins enables AML cells to resist chemotherapy and showed that disrupting the linkage could render the cells vulnerable to treatment.

The researchers believe their discovery could lead to drugs to enhance chemotherapy in patients with AML and other cancers.

John Schuetz, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues described this research in Nature Communications.

The team launched their experiments based on previous findings that a protein called ABCC4 was greatly elevated in aggressive cases of AML.

Dr Schuetz and his colleagues searched for other proteins that might interact with ABCC4 and enable its function. The team’s screening of candidate proteins yielded one, MPP1, which was also greatly increased in AML.

The researchers found the 2 proteins are connected, and the connection enables cells to assume the characteristics of highly proliferative leukemia cells.

These experiments involved genetically altering hematopoietic progenitor cells to have high MPP1 and ABCC4 levels. The cells were grown in culture and then replated to see if they would continue to grow, as such self-renewal is a hallmark of leukemia cells.

The researchers found that serial regrowth depended on the cells having high levels of both ABCC4 and MPP1.

“Typically, if you take normal progenitors and you replate, you could do that one time, maybe twice,” Dr Schuetz said. “But our big surprise was that overexpressing MPP1—analogous to what you would see in leukemia—allows those progenitors to self-renew, to be replated over and over, to form new colonies.”

The experiments also revealed that MPP1 and ABCC4 functioned at the cell membrane, where they could play a role in the machinery that would rid the leukemia cells of chemotherapy drugs.

“When we disrupted their interaction, ABCC4 moved off the membrane and the cells became more sensitive to drugs used in AML—drugs that are pumped out of the cell by ABCC4,” Dr Schuetz said.

By screening thousands of compounds, the researchers identified some that could disrupt the ABCC4-MPP1 connection. One, called Antimycin-A, reversed drug resistance in AML cell lines and in cells from AML patients.

Antimycin-A is too toxic to be used in chemotherapy, but the researchers believe identification of the compound should aid the search for other, less-toxic drugs to disrupt the ABCC4-MPP1 interaction.

The team’s findings could also enable clinicians to identify AML patients with high levels of ABCC4 and MPP1. In such patients, drugs that disrupt ABCC4-MPP1 might enhance the effectiveness of standard chemotherapy, Dr Schuetz said.

He also noted that other cancers, including breast and colon cancer and medulloblastoma, show high levels of both ABCC4 and MPP1. Chemotherapy for those cancers might also be enhanced by drugs that disrupt ABCC4-MPP1.

Children’s Research Hospital

Researchers say they have uncovered a target to overcome drug resistance in acute myeloid leukemia (AML).

The team discovered how a linkage between 2 proteins enables AML cells to resist chemotherapy and showed that disrupting the linkage could render the cells vulnerable to treatment.

The researchers believe their discovery could lead to drugs to enhance chemotherapy in patients with AML and other cancers.

John Schuetz, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues described this research in Nature Communications.

The team launched their experiments based on previous findings that a protein called ABCC4 was greatly elevated in aggressive cases of AML.

Dr Schuetz and his colleagues searched for other proteins that might interact with ABCC4 and enable its function. The team’s screening of candidate proteins yielded one, MPP1, which was also greatly increased in AML.

The researchers found the 2 proteins are connected, and the connection enables cells to assume the characteristics of highly proliferative leukemia cells.

These experiments involved genetically altering hematopoietic progenitor cells to have high MPP1 and ABCC4 levels. The cells were grown in culture and then replated to see if they would continue to grow, as such self-renewal is a hallmark of leukemia cells.

The researchers found that serial regrowth depended on the cells having high levels of both ABCC4 and MPP1.

“Typically, if you take normal progenitors and you replate, you could do that one time, maybe twice,” Dr Schuetz said. “But our big surprise was that overexpressing MPP1—analogous to what you would see in leukemia—allows those progenitors to self-renew, to be replated over and over, to form new colonies.”

The experiments also revealed that MPP1 and ABCC4 functioned at the cell membrane, where they could play a role in the machinery that would rid the leukemia cells of chemotherapy drugs.

“When we disrupted their interaction, ABCC4 moved off the membrane and the cells became more sensitive to drugs used in AML—drugs that are pumped out of the cell by ABCC4,” Dr Schuetz said.

By screening thousands of compounds, the researchers identified some that could disrupt the ABCC4-MPP1 connection. One, called Antimycin-A, reversed drug resistance in AML cell lines and in cells from AML patients.

Antimycin-A is too toxic to be used in chemotherapy, but the researchers believe identification of the compound should aid the search for other, less-toxic drugs to disrupt the ABCC4-MPP1 interaction.

The team’s findings could also enable clinicians to identify AML patients with high levels of ABCC4 and MPP1. In such patients, drugs that disrupt ABCC4-MPP1 might enhance the effectiveness of standard chemotherapy, Dr Schuetz said.

He also noted that other cancers, including breast and colon cancer and medulloblastoma, show high levels of both ABCC4 and MPP1. Chemotherapy for those cancers might also be enhanced by drugs that disrupt ABCC4-MPP1.

Clinical question: Does price transparency of laboratory tests at the point of order entry affect provider ordering behavior?

Background: Up to 30% of laboratory testing may be unnecessary, and health systems are seeking ways to effectively influence provider ordering of tests to reduce costs and improve value to patients. Price transparency and cost displaying is one strategy that has had mixed results in influencing provider ordering and reducing the amount of unnecessary laboratory testing.

Clinical question: Does price transparency of laboratory tests at the point of order entry affect provider ordering behavior?

Background: Up to 30% of laboratory testing may be unnecessary, and health systems are seeking ways to effectively influence provider ordering of tests to reduce costs and improve value to patients. Price transparency and cost displaying is one strategy that has had mixed results in influencing provider ordering and reducing the amount of unnecessary laboratory testing.

Clinical question: Does price transparency of laboratory tests at the point of order entry affect provider ordering behavior?

Background: Up to 30% of laboratory testing may be unnecessary, and health systems are seeking ways to effectively influence provider ordering of tests to reduce costs and improve value to patients. Price transparency and cost displaying is one strategy that has had mixed results in influencing provider ordering and reducing the amount of unnecessary laboratory testing.

The urate-lowering therapy febuxostat may have a higher risk of heart-related death than does another urate-lowering drug, allopurinol, according to a Safety Alert from the Food and Drug Administration.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The urate-lowering therapy febuxostat may have a higher risk of heart-related death than does another urate-lowering drug, allopurinol, according to a Safety Alert from the Food and Drug Administration.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The urate-lowering therapy febuxostat may have a higher risk of heart-related death than does another urate-lowering drug, allopurinol, according to a Safety Alert from the Food and Drug Administration.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Drug overdose is the leading cause of death for Americans under age 50. And the number of men and women dying from drug overdose shows no abating, with a sharp 17% increase in 2016 over 2015.¹ The rate of fatal overdoses rose to nearly 20 people per 100,000 in 2016, according to the Centers for Disease Control and Prevention. The highest death rates are reported in West Virginia, New Hampshire, Kentucky, Ohio, and Rhode Island.²

Dr. Andrew Kolodny, director of opioid policy research at Brandeis University, told The New York Times that there are “roughly two groups of Americans that are getting addicted. We have an older group that is overdosing on pain medicine, and we have a younger group that is overdosing on black market opioids.”¹

Are ObGyns contributing to the over-prescription of opioid pain medications? Investigators from Florida Hospital, the University of Florida, and Orlando VA Medical Center are researching the question, and preliminary findings indicate that, yes, in fact “gynecologists are overprescribing postoperative prescription opioids in all levels of gynecologic surgery,” including after laparotomies and major and minor minimally invasive surgeries. Their work thus far, a prospective cohort study involving 113 patients enrolled to date, was presented November 15, 2017, in Washington, DC, as part of the 46th AAGL Global Congress on MIGS. They found that, on average, patients were prescribed 29.6 (SD, 9.3) opioid tablets, and they had 19.1 (SD, 12.6) tablets left over after surgery. Not surprisingly, patients undergoing major minimally invasive surgery and laparotomy were prescribed larger amounts of opioids than those undergoing minor minimally invasive surgery, but the amount of pain medication left over was similar regardless of surgery type.

The researchers also asked patients if they were told how to dispose of their leftover opioids; only 3 patients reported being told what to do if they had leftover medication.

Too many pills prescribed

In separate research presented at the meeting, investigators from Tufts Medical Center and Lahey Hospital and Medical Center in Boston, Massachusetts, sought to determine opioid prescription practices and patient opioid use after benign hysterectomy. Using retrospective online physician and telephone patient surveys, they found that 51 gynecologists prescribed a median of 30 tabs of oxycodone or hydromorphone after abdominal hysterectomy and a median of 20 tabs after laparoscopic or vaginal hysterectomy. Nearly 65% (36/56) of women used less than half of the opioids they were prescribed, and 16.1% (9/56) used zero tabs. Opioid use was not found to be significantly different for women undergoing abdominal versus minimally invasive hysterectomy.

Managing pain expectations

It takes only 3 days of opioid use for a patient to be at risk for continued use (1 to 3 years) of opioids, said Georgine Lamvu, MD, MPH, CPE, in the educational session “Perioperative Management of the Chronic Pain Patient” at the AAGL meeting. And long-term opioid use is associated with addiction, misuse, and mortality.³ It is therefore crucial to understand how to prescribe pain medications and how to educate women on expectations of pain relief.

Dr. Lamvu and fellow presenters described a 4-step process to pain management: 1) assess—including taking a history and physical exam and providing a risk assessment; 2) check—for other medications that a patient may be taking and possible interactions, as well make sure that the patient is not obtaining opioids or benzodiazepines from other providers; 3) discuss—what pain expectations you have for the patient following surgery; and 4) observe—for clinical improvement, overuse, and misuse, and go slow with dose increases and consult support pain management teams when needed.

Overall, they recommended that surgeons perform a risk assessment (determine the risks and benefits of available therapies); educate themselves and their patients on the risks and benefits; and document the risk assessment, the final recommendations to the patient, and the education provided to the patient.

“We need to do a lot better job at educating ourselves and our patients about pain medications and pain management strategies,” said Dr. Lamvu. The presenters provided these key points for patient and family education:

• Opioids are not first-line or routine therapy for chronic pain, and for acute pain they are used only for severe pain and in short-duration amounts.
• Analgesia will not make you pain free. It only helps to alleviate some pain, and most pain medications take 1 to 2 hours to take effect.
• A 30% improvement in pain and function can be expected for most therapies.
• Recovery from surgical or acute traumatic injury is not immediate; it is expected to take 2 to 4 weeks.
• Do not take extra medication doses beyond what is prescribed, and tell all of your providers what medications you are taking.
• Do not stop taking opioids suddenly, instead taper the dose slowly as instructed by your provider.
• Dispose of excess drugs appropriately—by taking unused pills back to your provider or crushing the pills, placing them in a small amount of liquid, and putting them in the trash.

“The reality is that the majority of patients are not using as many pills as we give them,” said Dr. Lamvu. “Adequate pain control does not supersede patient safety or the responsibility that we have as providers to our society.”

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Drug overdose is the leading cause of death for Americans under age 50. And the number of men and women dying from drug overdose shows no abating, with a sharp 17% increase in 2016 over 2015.¹ The rate of fatal overdoses rose to nearly 20 people per 100,000 in 2016, according to the Centers for Disease Control and Prevention. The highest death rates are reported in West Virginia, New Hampshire, Kentucky, Ohio, and Rhode Island.²

Dr. Andrew Kolodny, director of opioid policy research at Brandeis University, told The New York Times that there are “roughly two groups of Americans that are getting addicted. We have an older group that is overdosing on pain medicine, and we have a younger group that is overdosing on black market opioids.”¹

Are ObGyns contributing to the over-prescription of opioid pain medications? Investigators from Florida Hospital, the University of Florida, and Orlando VA Medical Center are researching the question, and preliminary findings indicate that, yes, in fact “gynecologists are overprescribing postoperative prescription opioids in all levels of gynecologic surgery,” including after laparotomies and major and minor minimally invasive surgeries. Their work thus far, a prospective cohort study involving 113 patients enrolled to date, was presented November 15, 2017, in Washington, DC, as part of the 46th AAGL Global Congress on MIGS. They found that, on average, patients were prescribed 29.6 (SD, 9.3) opioid tablets, and they had 19.1 (SD, 12.6) tablets left over after surgery. Not surprisingly, patients undergoing major minimally invasive surgery and laparotomy were prescribed larger amounts of opioids than those undergoing minor minimally invasive surgery, but the amount of pain medication left over was similar regardless of surgery type.

The researchers also asked patients if they were told how to dispose of their leftover opioids; only 3 patients reported being told what to do if they had leftover medication.

Too many pills prescribed

In separate research presented at the meeting, investigators from Tufts Medical Center and Lahey Hospital and Medical Center in Boston, Massachusetts, sought to determine opioid prescription practices and patient opioid use after benign hysterectomy. Using retrospective online physician and telephone patient surveys, they found that 51 gynecologists prescribed a median of 30 tabs of oxycodone or hydromorphone after abdominal hysterectomy and a median of 20 tabs after laparoscopic or vaginal hysterectomy. Nearly 65% (36/56) of women used less than half of the opioids they were prescribed, and 16.1% (9/56) used zero tabs. Opioid use was not found to be significantly different for women undergoing abdominal versus minimally invasive hysterectomy.

Managing pain expectations

It takes only 3 days of opioid use for a patient to be at risk for continued use (1 to 3 years) of opioids, said Georgine Lamvu, MD, MPH, CPE, in the educational session “Perioperative Management of the Chronic Pain Patient” at the AAGL meeting. And long-term opioid use is associated with addiction, misuse, and mortality.³ It is therefore crucial to understand how to prescribe pain medications and how to educate women on expectations of pain relief.

Dr. Lamvu and fellow presenters described a 4-step process to pain management: 1) assess—including taking a history and physical exam and providing a risk assessment; 2) check—for other medications that a patient may be taking and possible interactions, as well make sure that the patient is not obtaining opioids or benzodiazepines from other providers; 3) discuss—what pain expectations you have for the patient following surgery; and 4) observe—for clinical improvement, overuse, and misuse, and go slow with dose increases and consult support pain management teams when needed.

Overall, they recommended that surgeons perform a risk assessment (determine the risks and benefits of available therapies); educate themselves and their patients on the risks and benefits; and document the risk assessment, the final recommendations to the patient, and the education provided to the patient.

“We need to do a lot better job at educating ourselves and our patients about pain medications and pain management strategies,” said Dr. Lamvu. The presenters provided these key points for patient and family education:

• Opioids are not first-line or routine therapy for chronic pain, and for acute pain they are used only for severe pain and in short-duration amounts.
• Analgesia will not make you pain free. It only helps to alleviate some pain, and most pain medications take 1 to 2 hours to take effect.
• A 30% improvement in pain and function can be expected for most therapies.
• Recovery from surgical or acute traumatic injury is not immediate; it is expected to take 2 to 4 weeks.
• Do not take extra medication doses beyond what is prescribed, and tell all of your providers what medications you are taking.
• Do not stop taking opioids suddenly, instead taper the dose slowly as instructed by your provider.
• Dispose of excess drugs appropriately—by taking unused pills back to your provider or crushing the pills, placing them in a small amount of liquid, and putting them in the trash.

“The reality is that the majority of patients are not using as many pills as we give them,” said Dr. Lamvu. “Adequate pain control does not supersede patient safety or the responsibility that we have as providers to our society.”

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Drug overdose is the leading cause of death for Americans under age 50. And the number of men and women dying from drug overdose shows no abating, with a sharp 17% increase in 2016 over 2015.¹ The rate of fatal overdoses rose to nearly 20 people per 100,000 in 2016, according to the Centers for Disease Control and Prevention. The highest death rates are reported in West Virginia, New Hampshire, Kentucky, Ohio, and Rhode Island.²

Dr. Andrew Kolodny, director of opioid policy research at Brandeis University, told The New York Times that there are “roughly two groups of Americans that are getting addicted. We have an older group that is overdosing on pain medicine, and we have a younger group that is overdosing on black market opioids.”¹

Are ObGyns contributing to the over-prescription of opioid pain medications? Investigators from Florida Hospital, the University of Florida, and Orlando VA Medical Center are researching the question, and preliminary findings indicate that, yes, in fact “gynecologists are overprescribing postoperative prescription opioids in all levels of gynecologic surgery,” including after laparotomies and major and minor minimally invasive surgeries. Their work thus far, a prospective cohort study involving 113 patients enrolled to date, was presented November 15, 2017, in Washington, DC, as part of the 46th AAGL Global Congress on MIGS. They found that, on average, patients were prescribed 29.6 (SD, 9.3) opioid tablets, and they had 19.1 (SD, 12.6) tablets left over after surgery. Not surprisingly, patients undergoing major minimally invasive surgery and laparotomy were prescribed larger amounts of opioids than those undergoing minor minimally invasive surgery, but the amount of pain medication left over was similar regardless of surgery type.

The researchers also asked patients if they were told how to dispose of their leftover opioids; only 3 patients reported being told what to do if they had leftover medication.

Too many pills prescribed

In separate research presented at the meeting, investigators from Tufts Medical Center and Lahey Hospital and Medical Center in Boston, Massachusetts, sought to determine opioid prescription practices and patient opioid use after benign hysterectomy. Using retrospective online physician and telephone patient surveys, they found that 51 gynecologists prescribed a median of 30 tabs of oxycodone or hydromorphone after abdominal hysterectomy and a median of 20 tabs after laparoscopic or vaginal hysterectomy. Nearly 65% (36/56) of women used less than half of the opioids they were prescribed, and 16.1% (9/56) used zero tabs. Opioid use was not found to be significantly different for women undergoing abdominal versus minimally invasive hysterectomy.

Managing pain expectations

It takes only 3 days of opioid use for a patient to be at risk for continued use (1 to 3 years) of opioids, said Georgine Lamvu, MD, MPH, CPE, in the educational session “Perioperative Management of the Chronic Pain Patient” at the AAGL meeting. And long-term opioid use is associated with addiction, misuse, and mortality.³ It is therefore crucial to understand how to prescribe pain medications and how to educate women on expectations of pain relief.

Dr. Lamvu and fellow presenters described a 4-step process to pain management: 1) assess—including taking a history and physical exam and providing a risk assessment; 2) check—for other medications that a patient may be taking and possible interactions, as well make sure that the patient is not obtaining opioids or benzodiazepines from other providers; 3) discuss—what pain expectations you have for the patient following surgery; and 4) observe—for clinical improvement, overuse, and misuse, and go slow with dose increases and consult support pain management teams when needed.

Overall, they recommended that surgeons perform a risk assessment (determine the risks and benefits of available therapies); educate themselves and their patients on the risks and benefits; and document the risk assessment, the final recommendations to the patient, and the education provided to the patient.

“We need to do a lot better job at educating ourselves and our patients about pain medications and pain management strategies,” said Dr. Lamvu. The presenters provided these key points for patient and family education:

• Opioids are not first-line or routine therapy for chronic pain, and for acute pain they are used only for severe pain and in short-duration amounts.
• Analgesia will not make you pain free. It only helps to alleviate some pain, and most pain medications take 1 to 2 hours to take effect.
• A 30% improvement in pain and function can be expected for most therapies.
• Recovery from surgical or acute traumatic injury is not immediate; it is expected to take 2 to 4 weeks.
• Do not take extra medication doses beyond what is prescribed, and tell all of your providers what medications you are taking.
• Do not stop taking opioids suddenly, instead taper the dose slowly as instructed by your provider.
• Dispose of excess drugs appropriately—by taking unused pills back to your provider or crushing the pills, placing them in a small amount of liquid, and putting them in the trash.

“The reality is that the majority of patients are not using as many pills as we give them,” said Dr. Lamvu. “Adequate pain control does not supersede patient safety or the responsibility that we have as providers to our society.”

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

SAN ANTONIO – Implementing universal paternal Rh screening would be a cost-effective safety strategy among patients receiving in vitro fertilization, according to a model that used up-to-date data and accounted for ethnic variations in the prevalence of the Rh (D) antibody.

Using a universal Rh screening strategy for semen donors to Rh (D) negative women undergoing in vitro fertilization would result in a cost savings of $11.01 per patient, or $1,120,000 per 100,000 Rh negative IVF pregnancies, according to Pietro Bortoletto, MD, and his coauthors. Their findings were presented during a poster session at the annual meeting of the American Society for Reproductive Medicine.

If paternal Rh factor status is unknown, vaginal bleeding during pregnancy prompts maternal administration of anti-D immune globulin if the mother is Rh (D) negative to prevent hemolytic disease of the fetus and newborn. However, wrote Dr. Bortoletto and his colleagues, “in the IVF population, where paternity status is presumed to be certain, the Rh (D) status of the male partner can be used to triage Rh (D) negative women to more appropriate administration of anti-D globulin.”

To see whether a universal paternal Rh screening strategy would be cost effective, Dr. Bortoletto, a resident physician in obstetrics and gynecology at Harvard Medical School and Brigham and Women’s Hospital, both in Boston, and his collaborators constructed a decision tree to estimate cost savings. The model compared a universal paternal-screening strategy for Rh (D) negative women undergoing IVF with the current standard of practice, which does not involve routine Rh (D) screening for the sperm donor.

In constructing the model, the investigators drew on published data showing that first trimester bleeding is more common in women who undergo IVF: It occurs in one-third of these women, compared with about 20% of the general pregnant population.

They also established probability estimates of pregnancy loss before 20 weeks, with and without first trimester bleeding (0.34 and 0.18, respectively); third trimester bleeding, with and without first trimester bleeding (0.05 and 0.02); and trauma in pregnancy (0.08). They estimated the overall probability of the pregnancy producing an Rh positive neonate at 0.62.

An additional factor that Dr. Bortoletto and his collaborators took into account was the variable prevalence of Rh factor by ethnicity; in the United States, it’s most common in white men and least common in Asian men, with intermediate prevalence in African American and Hispanic men.

When paternal ethnicity was included in the analysis, savings were greatest with white sperm donors, at $1,889,000 per 100,000 Rh negative IVF pregnancies. The lower prevalence of Rh factor in Asian men meant that the strategy was not cost effective in this population since it would cost a net $2,323,000 per 100,000 Rh negative IVF pregnancies.

“A targeted screening approach, by paternal ethnicity, may be a targeted strategy for cost reduction,” wrote Dr. Bortoletto and his colleagues.

Figures for cost estimates were drawn from data from the Centers for Medicare & Medicaid (CMS) using 2017 dollars. The cost for tests to determine blood type and Rh status ranged from $6 to $11, so the investigators set the cost estimate of $8.20. The cost for an antibody screen was estimated at $5.25 (range, $4-$7).

The cost for a 300 mcg dose of anti-D immune globulin was estimated at $93.93 (range, $79-$109), and administration costs were $27.04 (range, $25-$28). Kleihauer-Betke testing to determine the amount of fetal blood in maternal circulation was pinned at $10.61 (range, $8-$14).

Even when the lowest end of the cost range of anti-D immune globulin was used, a universal screening model would still realize a cost savings of $820,000 per 100,000 Rh negative IVF pregnancies. When Rh screening cost was set at $11 – at the high end of the range – “the strategy still remained favorable at $981,000,” wrote Dr. Bortoletto and his colleagues.

“Universal paternal Rh screening provides a cost saving intervention by preventing nonindicated and costly administration of anti-D immune globulin in the IVF population presenting with bleeding or trauma in pregnancy,” they wrote.

Dr. Bortoletto reported no outside sources of funding and no conflicts of interest.

[email protected]

On Twitter @karioakes

SAN ANTONIO – Implementing universal paternal Rh screening would be a cost-effective safety strategy among patients receiving in vitro fertilization, according to a model that used up-to-date data and accounted for ethnic variations in the prevalence of the Rh (D) antibody.

Using a universal Rh screening strategy for semen donors to Rh (D) negative women undergoing in vitro fertilization would result in a cost savings of $11.01 per patient, or $1,120,000 per 100,000 Rh negative IVF pregnancies, according to Pietro Bortoletto, MD, and his coauthors. Their findings were presented during a poster session at the annual meeting of the American Society for Reproductive Medicine.

If paternal Rh factor status is unknown, vaginal bleeding during pregnancy prompts maternal administration of anti-D immune globulin if the mother is Rh (D) negative to prevent hemolytic disease of the fetus and newborn. However, wrote Dr. Bortoletto and his colleagues, “in the IVF population, where paternity status is presumed to be certain, the Rh (D) status of the male partner can be used to triage Rh (D) negative women to more appropriate administration of anti-D globulin.”

To see whether a universal paternal Rh screening strategy would be cost effective, Dr. Bortoletto, a resident physician in obstetrics and gynecology at Harvard Medical School and Brigham and Women’s Hospital, both in Boston, and his collaborators constructed a decision tree to estimate cost savings. The model compared a universal paternal-screening strategy for Rh (D) negative women undergoing IVF with the current standard of practice, which does not involve routine Rh (D) screening for the sperm donor.

In constructing the model, the investigators drew on published data showing that first trimester bleeding is more common in women who undergo IVF: It occurs in one-third of these women, compared with about 20% of the general pregnant population.

They also established probability estimates of pregnancy loss before 20 weeks, with and without first trimester bleeding (0.34 and 0.18, respectively); third trimester bleeding, with and without first trimester bleeding (0.05 and 0.02); and trauma in pregnancy (0.08). They estimated the overall probability of the pregnancy producing an Rh positive neonate at 0.62.

An additional factor that Dr. Bortoletto and his collaborators took into account was the variable prevalence of Rh factor by ethnicity; in the United States, it’s most common in white men and least common in Asian men, with intermediate prevalence in African American and Hispanic men.

When paternal ethnicity was included in the analysis, savings were greatest with white sperm donors, at $1,889,000 per 100,000 Rh negative IVF pregnancies. The lower prevalence of Rh factor in Asian men meant that the strategy was not cost effective in this population since it would cost a net $2,323,000 per 100,000 Rh negative IVF pregnancies.

“A targeted screening approach, by paternal ethnicity, may be a targeted strategy for cost reduction,” wrote Dr. Bortoletto and his colleagues.

Figures for cost estimates were drawn from data from the Centers for Medicare & Medicaid (CMS) using 2017 dollars. The cost for tests to determine blood type and Rh status ranged from $6 to $11, so the investigators set the cost estimate of $8.20. The cost for an antibody screen was estimated at $5.25 (range, $4-$7).

The cost for a 300 mcg dose of anti-D immune globulin was estimated at $93.93 (range, $79-$109), and administration costs were $27.04 (range, $25-$28). Kleihauer-Betke testing to determine the amount of fetal blood in maternal circulation was pinned at $10.61 (range, $8-$14).

Even when the lowest end of the cost range of anti-D immune globulin was used, a universal screening model would still realize a cost savings of $820,000 per 100,000 Rh negative IVF pregnancies. When Rh screening cost was set at $11 – at the high end of the range – “the strategy still remained favorable at $981,000,” wrote Dr. Bortoletto and his colleagues.

“Universal paternal Rh screening provides a cost saving intervention by preventing nonindicated and costly administration of anti-D immune globulin in the IVF population presenting with bleeding or trauma in pregnancy,” they wrote.

Dr. Bortoletto reported no outside sources of funding and no conflicts of interest.

[email protected]

On Twitter @karioakes

SAN ANTONIO – Implementing universal paternal Rh screening would be a cost-effective safety strategy among patients receiving in vitro fertilization, according to a model that used up-to-date data and accounted for ethnic variations in the prevalence of the Rh (D) antibody.

Using a universal Rh screening strategy for semen donors to Rh (D) negative women undergoing in vitro fertilization would result in a cost savings of $11.01 per patient, or $1,120,000 per 100,000 Rh negative IVF pregnancies, according to Pietro Bortoletto, MD, and his coauthors. Their findings were presented during a poster session at the annual meeting of the American Society for Reproductive Medicine.

If paternal Rh factor status is unknown, vaginal bleeding during pregnancy prompts maternal administration of anti-D immune globulin if the mother is Rh (D) negative to prevent hemolytic disease of the fetus and newborn. However, wrote Dr. Bortoletto and his colleagues, “in the IVF population, where paternity status is presumed to be certain, the Rh (D) status of the male partner can be used to triage Rh (D) negative women to more appropriate administration of anti-D globulin.”

To see whether a universal paternal Rh screening strategy would be cost effective, Dr. Bortoletto, a resident physician in obstetrics and gynecology at Harvard Medical School and Brigham and Women’s Hospital, both in Boston, and his collaborators constructed a decision tree to estimate cost savings. The model compared a universal paternal-screening strategy for Rh (D) negative women undergoing IVF with the current standard of practice, which does not involve routine Rh (D) screening for the sperm donor.

In constructing the model, the investigators drew on published data showing that first trimester bleeding is more common in women who undergo IVF: It occurs in one-third of these women, compared with about 20% of the general pregnant population.

They also established probability estimates of pregnancy loss before 20 weeks, with and without first trimester bleeding (0.34 and 0.18, respectively); third trimester bleeding, with and without first trimester bleeding (0.05 and 0.02); and trauma in pregnancy (0.08). They estimated the overall probability of the pregnancy producing an Rh positive neonate at 0.62.

An additional factor that Dr. Bortoletto and his collaborators took into account was the variable prevalence of Rh factor by ethnicity; in the United States, it’s most common in white men and least common in Asian men, with intermediate prevalence in African American and Hispanic men.

When paternal ethnicity was included in the analysis, savings were greatest with white sperm donors, at $1,889,000 per 100,000 Rh negative IVF pregnancies. The lower prevalence of Rh factor in Asian men meant that the strategy was not cost effective in this population since it would cost a net $2,323,000 per 100,000 Rh negative IVF pregnancies.

“A targeted screening approach, by paternal ethnicity, may be a targeted strategy for cost reduction,” wrote Dr. Bortoletto and his colleagues.

Figures for cost estimates were drawn from data from the Centers for Medicare & Medicaid (CMS) using 2017 dollars. The cost for tests to determine blood type and Rh status ranged from $6 to $11, so the investigators set the cost estimate of $8.20. The cost for an antibody screen was estimated at $5.25 (range, $4-$7).

The cost for a 300 mcg dose of anti-D immune globulin was estimated at $93.93 (range, $79-$109), and administration costs were $27.04 (range, $25-$28). Kleihauer-Betke testing to determine the amount of fetal blood in maternal circulation was pinned at $10.61 (range, $8-$14).

Even when the lowest end of the cost range of anti-D immune globulin was used, a universal screening model would still realize a cost savings of $820,000 per 100,000 Rh negative IVF pregnancies. When Rh screening cost was set at $11 – at the high end of the range – “the strategy still remained favorable at $981,000,” wrote Dr. Bortoletto and his colleagues.

“Universal paternal Rh screening provides a cost saving intervention by preventing nonindicated and costly administration of anti-D immune globulin in the IVF population presenting with bleeding or trauma in pregnancy,” they wrote.

Dr. Bortoletto reported no outside sources of funding and no conflicts of interest.

[email protected]

On Twitter @karioakes

For 44 years, the latest pharmacologic, radiologic, surgical, and endovascular techniques and technologies have been presented at the VEITHsymposium, along with discussions of when these treatments are indicated. Updates on clinical trials and opportunities for dialogue with experts in the field provide insight along with the latest results of the various treatment modalities.

This information is packed into a single meeting with as many short presentations as possible - some  of them concurrent. Access has been facilitated by providing electronically archived material, including talks, slides, and panels after the meeting.  

To avoid the conundrum of having to choose between concurrent sessions, meeting attendees can access them through this year’s online library, which can be found at www.veithondemand.com. For individuals unable to attend the meeting, the online library is CME accredited so that they may receive credit for their educational viewing experience. 

VEITHsymposium has partnered with Edge Creek Media, Inc. to digitally capture the presentations from this year’s event and make them available online for cross-platform and mobile device viewing. Each webcast presentation will be produced with synchronous presenter audio, and slide content to reproduce  the presentations.  

The online library will contain over 1,200 webcast presentations and will include presentations from approximately 600 expert speakers. This library will recreate the remarkable educational experience of attending in person. It will also provide an invaluable resource of ongoing vascular information.  

Edge Creek Media is a specialized multimedia production company that offers custom live event recording and webcast streaming solutions. Other core services include mobile app development, live event production, audio/video post production, and multimedia web development. 

For more information, visit www.edgecreekmedia.com or contact the company at [email protected]. ■

For 44 years, the latest pharmacologic, radiologic, surgical, and endovascular techniques and technologies have been presented at the VEITHsymposium, along with discussions of when these treatments are indicated. Updates on clinical trials and opportunities for dialogue with experts in the field provide insight along with the latest results of the various treatment modalities.

This information is packed into a single meeting with as many short presentations as possible - some  of them concurrent. Access has been facilitated by providing electronically archived material, including talks, slides, and panels after the meeting.  

To avoid the conundrum of having to choose between concurrent sessions, meeting attendees can access them through this year’s online library, which can be found at www.veithondemand.com. For individuals unable to attend the meeting, the online library is CME accredited so that they may receive credit for their educational viewing experience. 

VEITHsymposium has partnered with Edge Creek Media, Inc. to digitally capture the presentations from this year’s event and make them available online for cross-platform and mobile device viewing. Each webcast presentation will be produced with synchronous presenter audio, and slide content to reproduce  the presentations.  

The online library will contain over 1,200 webcast presentations and will include presentations from approximately 600 expert speakers. This library will recreate the remarkable educational experience of attending in person. It will also provide an invaluable resource of ongoing vascular information.  

Edge Creek Media is a specialized multimedia production company that offers custom live event recording and webcast streaming solutions. Other core services include mobile app development, live event production, audio/video post production, and multimedia web development. 

For more information, visit www.edgecreekmedia.com or contact the company at [email protected]. ■

For 44 years, the latest pharmacologic, radiologic, surgical, and endovascular techniques and technologies have been presented at the VEITHsymposium, along with discussions of when these treatments are indicated. Updates on clinical trials and opportunities for dialogue with experts in the field provide insight along with the latest results of the various treatment modalities.

This information is packed into a single meeting with as many short presentations as possible - some  of them concurrent. Access has been facilitated by providing electronically archived material, including talks, slides, and panels after the meeting.  

To avoid the conundrum of having to choose between concurrent sessions, meeting attendees can access them through this year’s online library, which can be found at www.veithondemand.com. For individuals unable to attend the meeting, the online library is CME accredited so that they may receive credit for their educational viewing experience. 

VEITHsymposium has partnered with Edge Creek Media, Inc. to digitally capture the presentations from this year’s event and make them available online for cross-platform and mobile device viewing. Each webcast presentation will be produced with synchronous presenter audio, and slide content to reproduce  the presentations.  

The online library will contain over 1,200 webcast presentations and will include presentations from approximately 600 expert speakers. This library will recreate the remarkable educational experience of attending in person. It will also provide an invaluable resource of ongoing vascular information.  

Edge Creek Media is a specialized multimedia production company that offers custom live event recording and webcast streaming solutions. Other core services include mobile app development, live event production, audio/video post production, and multimedia web development. 

For more information, visit www.edgecreekmedia.com or contact the company at [email protected]. ■

Stenting improved outcomes in patients with chronic obstruction of the inferior vena cava (IVC), according to a retrospective analysis of medical records from March 2010 to September 2015.

In the study, 19 of 20 patients with chronic IVC obstruction had successful stent placement, with most resulting in improved and sustained clinical outcomes. The study, conducted by Ole Jørgen Grøtta, MD, and colleagues, was reported in the European Journal of Vascular and Endovascular Surgery (2017;54:620-8).

Dr. Grøtta and colleagues investigated 11 men and 9 women patients, with a median age 43years, and with venography-verified chronic IVC obstruction. Most patients also were screened and found to be positive for thrombophilia. Median follow-up was 25 months (range, 3-70 months).

The researchers reported on 13 patients with IVC occlusion and 7 with stenosis. Patient clinical status and symptom severity was assessed according to standardized CEAP (clinical, etiology, anatomy and pathophysiology) classification and the venous clinical severity score (VCSS), respectively. Sixteen patients presented chronic venous disease (CVD) symptoms in their lower limbs; of these, nine exhibited symptoms of an acute thrombosis and, based on their symptoms, seven were assigned to a specific CEAP category, ranging from C3-C6. The additional four patients included in the study had been referred to receive endovascular treatment intervention based on symptoms consistent with physical activity–related reduced cardiac preload.

A total of 13 of 19 (68%) patients showed sustained and significant clinical improvement, seen as a shift from the baseline VCSS score of 8.5 down to 7.0 (P = .007) at final follow-up. This included all four of the patients identified as having reduced cardiac preload problems. The authors also reported that here were no periprocedural or long-term complications.

The need for an alternative treatment for patients with chronic obstruction of the IVC is exemplified by typically poor sustained clinical improvement outcomes and/or gradual clinical deterioration when using the traditional conservative approach of anticoagulants combined with compression stockings, according to the authors.

“The endovascular approach with stent placement for chronic IVC obstructions is a safe treatment alternative that should be offered to patients who otherwise have little opportunity for clinical improvement,” they concluded.

The authors reported that they had no conflicts of interest.
 

Stenting improved outcomes in patients with chronic obstruction of the inferior vena cava (IVC), according to a retrospective analysis of medical records from March 2010 to September 2015.

In the study, 19 of 20 patients with chronic IVC obstruction had successful stent placement, with most resulting in improved and sustained clinical outcomes. The study, conducted by Ole Jørgen Grøtta, MD, and colleagues, was reported in the European Journal of Vascular and Endovascular Surgery (2017;54:620-8).

Dr. Grøtta and colleagues investigated 11 men and 9 women patients, with a median age 43years, and with venography-verified chronic IVC obstruction. Most patients also were screened and found to be positive for thrombophilia. Median follow-up was 25 months (range, 3-70 months).

The researchers reported on 13 patients with IVC occlusion and 7 with stenosis. Patient clinical status and symptom severity was assessed according to standardized CEAP (clinical, etiology, anatomy and pathophysiology) classification and the venous clinical severity score (VCSS), respectively. Sixteen patients presented chronic venous disease (CVD) symptoms in their lower limbs; of these, nine exhibited symptoms of an acute thrombosis and, based on their symptoms, seven were assigned to a specific CEAP category, ranging from C3-C6. The additional four patients included in the study had been referred to receive endovascular treatment intervention based on symptoms consistent with physical activity–related reduced cardiac preload.

A total of 13 of 19 (68%) patients showed sustained and significant clinical improvement, seen as a shift from the baseline VCSS score of 8.5 down to 7.0 (P = .007) at final follow-up. This included all four of the patients identified as having reduced cardiac preload problems. The authors also reported that here were no periprocedural or long-term complications.

The need for an alternative treatment for patients with chronic obstruction of the IVC is exemplified by typically poor sustained clinical improvement outcomes and/or gradual clinical deterioration when using the traditional conservative approach of anticoagulants combined with compression stockings, according to the authors.

“The endovascular approach with stent placement for chronic IVC obstructions is a safe treatment alternative that should be offered to patients who otherwise have little opportunity for clinical improvement,” they concluded.

The authors reported that they had no conflicts of interest.
 

Stenting improved outcomes in patients with chronic obstruction of the inferior vena cava (IVC), according to a retrospective analysis of medical records from March 2010 to September 2015.

In the study, 19 of 20 patients with chronic IVC obstruction had successful stent placement, with most resulting in improved and sustained clinical outcomes. The study, conducted by Ole Jørgen Grøtta, MD, and colleagues, was reported in the European Journal of Vascular and Endovascular Surgery (2017;54:620-8).

Dr. Grøtta and colleagues investigated 11 men and 9 women patients, with a median age 43years, and with venography-verified chronic IVC obstruction. Most patients also were screened and found to be positive for thrombophilia. Median follow-up was 25 months (range, 3-70 months).

The researchers reported on 13 patients with IVC occlusion and 7 with stenosis. Patient clinical status and symptom severity was assessed according to standardized CEAP (clinical, etiology, anatomy and pathophysiology) classification and the venous clinical severity score (VCSS), respectively. Sixteen patients presented chronic venous disease (CVD) symptoms in their lower limbs; of these, nine exhibited symptoms of an acute thrombosis and, based on their symptoms, seven were assigned to a specific CEAP category, ranging from C3-C6. The additional four patients included in the study had been referred to receive endovascular treatment intervention based on symptoms consistent with physical activity–related reduced cardiac preload.

A total of 13 of 19 (68%) patients showed sustained and significant clinical improvement, seen as a shift from the baseline VCSS score of 8.5 down to 7.0 (P = .007) at final follow-up. This included all four of the patients identified as having reduced cardiac preload problems. The authors also reported that here were no periprocedural or long-term complications.

The need for an alternative treatment for patients with chronic obstruction of the IVC is exemplified by typically poor sustained clinical improvement outcomes and/or gradual clinical deterioration when using the traditional conservative approach of anticoagulants combined with compression stockings, according to the authors.

“The endovascular approach with stent placement for chronic IVC obstructions is a safe treatment alternative that should be offered to patients who otherwise have little opportunity for clinical improvement,” they concluded.

The authors reported that they had no conflicts of interest.