About 10% to 15% of women in the US have postpartum depression (PPD)—but that estimate is based mostly on women of European ancestry. In black women the rates are doubled, and among Latinas the prevalence is 30% to 43%. But those 2 groups have been inadequately studied, say researchers from University of North Carolina. To help remedy the lack of information, they conducted a study with the largest and “most robustly phenotyped” cohort of minority women with PPD. Their study also is the first to examine genetic ancestry as it contributes to PPD risk.

The researchers recruited 549 women with PPD and 968 without PPD who were within 6 weeks of having given birth. Of those, 67.4% were black, 14.4% were Latina, and 18.2% were white. The median age was 26.7; nearly half of the participants were married. Only 3.6% had given birth for the first time.

The women completed a battery of tests, including the Abuse and Trauma Inventory, Everyday Stressors Index (ESI), Edinburgh Postnatal Depression Scale (EPDS), and Postpartum Bonding Questionnaire. The researchers also assessed estradiol, progesterone, brain-derived neurotrophic factor, oxytocin, and allopregnanolone.

The women with PPD had significantly higher rates of previous psychiatric diagnoses, significantly higher EPDS total scores, and higher rates of family history of PPD. They also had significantly higher rates of previous diagnoses of major depressive disorder (MDD) (53% vs 15%), although 47% were experiencing their first episode of MDD. Dramatically higher numbers of women with PPD vs without PPD had suicidal thoughts in the month prior to assessment: 36% vs 2%, respectively.

Genetic ancestry was not predictive of case status, nor were hormonal influences any different between the 2 groups. Instead, psychiatric history and exposure to adverse life events were significant predictors. Nearly half of all the women with PPD had a lifetime anxiety disorder diagnosis compared with 7% of the controls. And although 67% of all participants reported a history of ≥ 1 traumatic event, women with PPD had double the proportion of multiple events of abuse and trauma. Women who had experienced multiple adverse life events were 3 times more likely to have PPD. Childhood and adult sexual abuse and life-threatening attack were among the most predictive.

The women with PPD had an ESI score > 3 times higher than that of the controls (19% vs 6%, respectively). The researchers note that cumulative lifetime stress may lead to epigenetic modification, and thus to PPD. Women with PPD also had a significantly higher proportion of dysfunctional mother-infant relationships, although the numbers were low in both groups (7% vs 0.35%, respectively).

The researchers say that although genetic ancestry did not play a role in determining case status, there are important ethnic and cultural differences that do play a role in treatment. For instance, Latinas and black women may be less likely to accept antidepressants as therapy. And because socioeconomic status is a determinant of health care access, they also face major barriers to mental health care. However, neither insurance nor education status (markers of socioeconomic status) distinguished cases from controls, even when the researchers controlled for genetic ancestry.

Their data provide a set of risk factors that can be used in screening new mothers, the researchers say. A brief, single assessment for previous psychiatric and abuse/trauma history during the perinatal period, along with regular mood monitoring, could increase a clinician’s ability to predict the onset of PPD.

Source:
Guintivano J, Sullivan PF, Stuebe AM. Psychol Med. 2018;48(7):1190-1200.
doi: 10.1017/S0033291717002641.

About 10% to 15% of women in the US have postpartum depression (PPD)—but that estimate is based mostly on women of European ancestry. In black women the rates are doubled, and among Latinas the prevalence is 30% to 43%. But those 2 groups have been inadequately studied, say researchers from University of North Carolina. To help remedy the lack of information, they conducted a study with the largest and “most robustly phenotyped” cohort of minority women with PPD. Their study also is the first to examine genetic ancestry as it contributes to PPD risk.

The researchers recruited 549 women with PPD and 968 without PPD who were within 6 weeks of having given birth. Of those, 67.4% were black, 14.4% were Latina, and 18.2% were white. The median age was 26.7; nearly half of the participants were married. Only 3.6% had given birth for the first time.

The women completed a battery of tests, including the Abuse and Trauma Inventory, Everyday Stressors Index (ESI), Edinburgh Postnatal Depression Scale (EPDS), and Postpartum Bonding Questionnaire. The researchers also assessed estradiol, progesterone, brain-derived neurotrophic factor, oxytocin, and allopregnanolone.

The women with PPD had significantly higher rates of previous psychiatric diagnoses, significantly higher EPDS total scores, and higher rates of family history of PPD. They also had significantly higher rates of previous diagnoses of major depressive disorder (MDD) (53% vs 15%), although 47% were experiencing their first episode of MDD. Dramatically higher numbers of women with PPD vs without PPD had suicidal thoughts in the month prior to assessment: 36% vs 2%, respectively.

Genetic ancestry was not predictive of case status, nor were hormonal influences any different between the 2 groups. Instead, psychiatric history and exposure to adverse life events were significant predictors. Nearly half of all the women with PPD had a lifetime anxiety disorder diagnosis compared with 7% of the controls. And although 67% of all participants reported a history of ≥ 1 traumatic event, women with PPD had double the proportion of multiple events of abuse and trauma. Women who had experienced multiple adverse life events were 3 times more likely to have PPD. Childhood and adult sexual abuse and life-threatening attack were among the most predictive.

The women with PPD had an ESI score > 3 times higher than that of the controls (19% vs 6%, respectively). The researchers note that cumulative lifetime stress may lead to epigenetic modification, and thus to PPD. Women with PPD also had a significantly higher proportion of dysfunctional mother-infant relationships, although the numbers were low in both groups (7% vs 0.35%, respectively).

The researchers say that although genetic ancestry did not play a role in determining case status, there are important ethnic and cultural differences that do play a role in treatment. For instance, Latinas and black women may be less likely to accept antidepressants as therapy. And because socioeconomic status is a determinant of health care access, they also face major barriers to mental health care. However, neither insurance nor education status (markers of socioeconomic status) distinguished cases from controls, even when the researchers controlled for genetic ancestry.

Their data provide a set of risk factors that can be used in screening new mothers, the researchers say. A brief, single assessment for previous psychiatric and abuse/trauma history during the perinatal period, along with regular mood monitoring, could increase a clinician’s ability to predict the onset of PPD.

Source:
Guintivano J, Sullivan PF, Stuebe AM. Psychol Med. 2018;48(7):1190-1200.
doi: 10.1017/S0033291717002641.

About 10% to 15% of women in the US have postpartum depression (PPD)—but that estimate is based mostly on women of European ancestry. In black women the rates are doubled, and among Latinas the prevalence is 30% to 43%. But those 2 groups have been inadequately studied, say researchers from University of North Carolina. To help remedy the lack of information, they conducted a study with the largest and “most robustly phenotyped” cohort of minority women with PPD. Their study also is the first to examine genetic ancestry as it contributes to PPD risk.

The researchers recruited 549 women with PPD and 968 without PPD who were within 6 weeks of having given birth. Of those, 67.4% were black, 14.4% were Latina, and 18.2% were white. The median age was 26.7; nearly half of the participants were married. Only 3.6% had given birth for the first time.

The women completed a battery of tests, including the Abuse and Trauma Inventory, Everyday Stressors Index (ESI), Edinburgh Postnatal Depression Scale (EPDS), and Postpartum Bonding Questionnaire. The researchers also assessed estradiol, progesterone, brain-derived neurotrophic factor, oxytocin, and allopregnanolone.

The women with PPD had significantly higher rates of previous psychiatric diagnoses, significantly higher EPDS total scores, and higher rates of family history of PPD. They also had significantly higher rates of previous diagnoses of major depressive disorder (MDD) (53% vs 15%), although 47% were experiencing their first episode of MDD. Dramatically higher numbers of women with PPD vs without PPD had suicidal thoughts in the month prior to assessment: 36% vs 2%, respectively.

Genetic ancestry was not predictive of case status, nor were hormonal influences any different between the 2 groups. Instead, psychiatric history and exposure to adverse life events were significant predictors. Nearly half of all the women with PPD had a lifetime anxiety disorder diagnosis compared with 7% of the controls. And although 67% of all participants reported a history of ≥ 1 traumatic event, women with PPD had double the proportion of multiple events of abuse and trauma. Women who had experienced multiple adverse life events were 3 times more likely to have PPD. Childhood and adult sexual abuse and life-threatening attack were among the most predictive.

The women with PPD had an ESI score > 3 times higher than that of the controls (19% vs 6%, respectively). The researchers note that cumulative lifetime stress may lead to epigenetic modification, and thus to PPD. Women with PPD also had a significantly higher proportion of dysfunctional mother-infant relationships, although the numbers were low in both groups (7% vs 0.35%, respectively).

The researchers say that although genetic ancestry did not play a role in determining case status, there are important ethnic and cultural differences that do play a role in treatment. For instance, Latinas and black women may be less likely to accept antidepressants as therapy. And because socioeconomic status is a determinant of health care access, they also face major barriers to mental health care. However, neither insurance nor education status (markers of socioeconomic status) distinguished cases from controls, even when the researchers controlled for genetic ancestry.

Their data provide a set of risk factors that can be used in screening new mothers, the researchers say. A brief, single assessment for previous psychiatric and abuse/trauma history during the perinatal period, along with regular mood monitoring, could increase a clinician’s ability to predict the onset of PPD.

Source:
Guintivano J, Sullivan PF, Stuebe AM. Psychol Med. 2018;48(7):1190-1200.
doi: 10.1017/S0033291717002641.

Photo by Patrick Pelletier

The availability of generic imatinib has had limited effects on costs of the drug, according to research published in Health Affairs.

Data suggest the cost of Gleevec in the US has more than doubled since the drug was approved in 2001, and the introduction of generic imatinib has reduced costs only slightly.

Two years after generic imatinib hit the market, a month’s supply of Gleevec cost about $9000, and the cost for generic imatinib was about $8000.

“Patients and providers have all looked forward to generic entry, expecting major price reductions,” said study author Stacie Dusetzina, PhD, of Vanderbilt University School of Medicine in Nashville, Tennessee.

“Unfortunately, we don’t see prices drop as quickly and as low as we would hope when generics are available.”

For this study, Dr Dusetzina and a colleague analyzed data from the MarketScan Commercial Research Database. The database contained records of 139,233 prescription fills for imatinib, which were made by 7201 patients from May 2001 through September 2017.

The researchers noted that Gleevec was priced at nearly $4000 for a 1-month (400 mg) supply when it came on the market in 2001. That price escalated to nearly $10,000 by 2015 before a generic competitor entered the market.

However, prices for Gleevec and generic imatinib remained high 2 years later. In 2017, a month’s supply of Gleevec cost about $9000, and the cost of generic imatinib was about $8000.

The researchers said the Gleevec case demonstrates several potential barriers to effective generic price competition, including shifts in prescribing toward more expensive brand-name treatments and smaller-than-expected price reductions.

Twenty-four percent of imatinib (Gleevec) prescriptions claims were for “dispense as written,” according to the researchers. This suggests that patients or providers specifically wanted to stay on the brand-name drug instead of switching to the generic.

“The more than doubling of the drug price over time and the lack of price reductions observed with nearly 2 years of generic drug competition is concerning,” Dr Dusetzina said.

“It begs the question whether we can rely on generic entry as a primary approach to address drug pricing for high-priced specialty medications. We need robust competition to move prices in this space.”

Photo by Patrick Pelletier

The availability of generic imatinib has had limited effects on costs of the drug, according to research published in Health Affairs.

Data suggest the cost of Gleevec in the US has more than doubled since the drug was approved in 2001, and the introduction of generic imatinib has reduced costs only slightly.

Two years after generic imatinib hit the market, a month’s supply of Gleevec cost about $9000, and the cost for generic imatinib was about $8000.

“Patients and providers have all looked forward to generic entry, expecting major price reductions,” said study author Stacie Dusetzina, PhD, of Vanderbilt University School of Medicine in Nashville, Tennessee.

“Unfortunately, we don’t see prices drop as quickly and as low as we would hope when generics are available.”

For this study, Dr Dusetzina and a colleague analyzed data from the MarketScan Commercial Research Database. The database contained records of 139,233 prescription fills for imatinib, which were made by 7201 patients from May 2001 through September 2017.

The researchers noted that Gleevec was priced at nearly $4000 for a 1-month (400 mg) supply when it came on the market in 2001. That price escalated to nearly $10,000 by 2015 before a generic competitor entered the market.

However, prices for Gleevec and generic imatinib remained high 2 years later. In 2017, a month’s supply of Gleevec cost about $9000, and the cost of generic imatinib was about $8000.

The researchers said the Gleevec case demonstrates several potential barriers to effective generic price competition, including shifts in prescribing toward more expensive brand-name treatments and smaller-than-expected price reductions.

Twenty-four percent of imatinib (Gleevec) prescriptions claims were for “dispense as written,” according to the researchers. This suggests that patients or providers specifically wanted to stay on the brand-name drug instead of switching to the generic.

“The more than doubling of the drug price over time and the lack of price reductions observed with nearly 2 years of generic drug competition is concerning,” Dr Dusetzina said.

“It begs the question whether we can rely on generic entry as a primary approach to address drug pricing for high-priced specialty medications. We need robust competition to move prices in this space.”

Photo by Patrick Pelletier

The availability of generic imatinib has had limited effects on costs of the drug, according to research published in Health Affairs.

Data suggest the cost of Gleevec in the US has more than doubled since the drug was approved in 2001, and the introduction of generic imatinib has reduced costs only slightly.

Two years after generic imatinib hit the market, a month’s supply of Gleevec cost about $9000, and the cost for generic imatinib was about $8000.

“Patients and providers have all looked forward to generic entry, expecting major price reductions,” said study author Stacie Dusetzina, PhD, of Vanderbilt University School of Medicine in Nashville, Tennessee.

“Unfortunately, we don’t see prices drop as quickly and as low as we would hope when generics are available.”

For this study, Dr Dusetzina and a colleague analyzed data from the MarketScan Commercial Research Database. The database contained records of 139,233 prescription fills for imatinib, which were made by 7201 patients from May 2001 through September 2017.

The researchers noted that Gleevec was priced at nearly $4000 for a 1-month (400 mg) supply when it came on the market in 2001. That price escalated to nearly $10,000 by 2015 before a generic competitor entered the market.

However, prices for Gleevec and generic imatinib remained high 2 years later. In 2017, a month’s supply of Gleevec cost about $9000, and the cost of generic imatinib was about $8000.

The researchers said the Gleevec case demonstrates several potential barriers to effective generic price competition, including shifts in prescribing toward more expensive brand-name treatments and smaller-than-expected price reductions.

Twenty-four percent of imatinib (Gleevec) prescriptions claims were for “dispense as written,” according to the researchers. This suggests that patients or providers specifically wanted to stay on the brand-name drug instead of switching to the generic.

“The more than doubling of the drug price over time and the lack of price reductions observed with nearly 2 years of generic drug competition is concerning,” Dr Dusetzina said.

“It begs the question whether we can rely on generic entry as a primary approach to address drug pricing for high-priced specialty medications. We need robust competition to move prices in this space.”

Henrique Orlandi Mourao

Researchers have discovered the first leukemia-protective gene that is specific to the Y chromosome, according to an article published in Nature Genetics.

The researchers were investigating how loss of the X-chromosome gene UTX hastens the development of acute myeloid leukemia (AML).

However, they found that UTY, a related gene on the Y chromosome, protected male mice lacking UTX from developing AML.

The researchers then found that, in AML and other cancers, loss of UTX is accompanied by loss of UTY.

“This is the first Y chromosome-specific gene that protects against AML,” said study author Malgorzata Gozdecka, PhD, of the Wellcome Sanger Institute in Hinxton, UK.

“Previously, it had been suggested that the only function of the Y chromosome is in creating male sexual characteristics, but our results indicate that the Y chromosome could also protect against AML and other cancers.”

For this work, Dr Gozdecka and her colleagues studied the UTX gene in human cells and mice.

In addition to their discovery that UTY acts as a tumor suppressor gene, the researchers uncovered a new mechanism for how loss of UTX leads to AML.

They discovered that UTX acts as a common scaffold, bringing together a large number of regulatory proteins that control access to DNA and gene expression, a function that can also be carried out by UTY.

Specifically, the team said UTX suppresses AML by repressing oncogenic ETS and upregulating tumor-suppressive GATA programs. And loss of UTX leads to “altered patterns of gene expression that induce and maintain” AML.

“Treatments for AML have not changed in decades, and there is a large unmet need for new therapies,” said study author George Vassiliou, PhD, of the Wellcome Sanger Institute.

“This study helps us understand the development of AML and gives us clues for developing new drug targets to disrupt leukemia-causing processes. We hope this study will enable new lines of research for the development of previously unforeseen treatments and improve the lives of patients with AML.”

Henrique Orlandi Mourao

Researchers have discovered the first leukemia-protective gene that is specific to the Y chromosome, according to an article published in Nature Genetics.

The researchers were investigating how loss of the X-chromosome gene UTX hastens the development of acute myeloid leukemia (AML).

However, they found that UTY, a related gene on the Y chromosome, protected male mice lacking UTX from developing AML.

The researchers then found that, in AML and other cancers, loss of UTX is accompanied by loss of UTY.

“This is the first Y chromosome-specific gene that protects against AML,” said study author Malgorzata Gozdecka, PhD, of the Wellcome Sanger Institute in Hinxton, UK.

“Previously, it had been suggested that the only function of the Y chromosome is in creating male sexual characteristics, but our results indicate that the Y chromosome could also protect against AML and other cancers.”

For this work, Dr Gozdecka and her colleagues studied the UTX gene in human cells and mice.

In addition to their discovery that UTY acts as a tumor suppressor gene, the researchers uncovered a new mechanism for how loss of UTX leads to AML.

They discovered that UTX acts as a common scaffold, bringing together a large number of regulatory proteins that control access to DNA and gene expression, a function that can also be carried out by UTY.

Specifically, the team said UTX suppresses AML by repressing oncogenic ETS and upregulating tumor-suppressive GATA programs. And loss of UTX leads to “altered patterns of gene expression that induce and maintain” AML.

“Treatments for AML have not changed in decades, and there is a large unmet need for new therapies,” said study author George Vassiliou, PhD, of the Wellcome Sanger Institute.

“This study helps us understand the development of AML and gives us clues for developing new drug targets to disrupt leukemia-causing processes. We hope this study will enable new lines of research for the development of previously unforeseen treatments and improve the lives of patients with AML.”

Henrique Orlandi Mourao

Researchers have discovered the first leukemia-protective gene that is specific to the Y chromosome, according to an article published in Nature Genetics.

The researchers were investigating how loss of the X-chromosome gene UTX hastens the development of acute myeloid leukemia (AML).

However, they found that UTY, a related gene on the Y chromosome, protected male mice lacking UTX from developing AML.

The researchers then found that, in AML and other cancers, loss of UTX is accompanied by loss of UTY.

“This is the first Y chromosome-specific gene that protects against AML,” said study author Malgorzata Gozdecka, PhD, of the Wellcome Sanger Institute in Hinxton, UK.

“Previously, it had been suggested that the only function of the Y chromosome is in creating male sexual characteristics, but our results indicate that the Y chromosome could also protect against AML and other cancers.”

For this work, Dr Gozdecka and her colleagues studied the UTX gene in human cells and mice.

In addition to their discovery that UTY acts as a tumor suppressor gene, the researchers uncovered a new mechanism for how loss of UTX leads to AML.

They discovered that UTX acts as a common scaffold, bringing together a large number of regulatory proteins that control access to DNA and gene expression, a function that can also be carried out by UTY.

Specifically, the team said UTX suppresses AML by repressing oncogenic ETS and upregulating tumor-suppressive GATA programs. And loss of UTX leads to “altered patterns of gene expression that induce and maintain” AML.

“Treatments for AML have not changed in decades, and there is a large unmet need for new therapies,” said study author George Vassiliou, PhD, of the Wellcome Sanger Institute.

“This study helps us understand the development of AML and gives us clues for developing new drug targets to disrupt leukemia-causing processes. We hope this study will enable new lines of research for the development of previously unforeseen treatments and improve the lives of patients with AML.”

Image courtesy of AFIP

Preclinical research helps explain how the JAK1/2 inhibitor ruxolitinib can reduce thrombosis in patients with myeloproliferative neoplasms (MPNs).

Experiments revealed a link between JAK2^V617F and the formation of neutrophil extracellular traps (NETs), which have been implicated in thrombosis.

Researchers found that ruxolitinib reduced NET formation and decreased thrombosis in JAK2-mutant mice.

Benjamin L. Ebert, MD, PhD, of Brigham and Women’s Hospital in Boston, Massachusetts, and his colleagues reported these findings in Science Translational Medicine.

The researchers noted that patients with MPNs have an increased risk of thrombosis, and previous research linked thrombosis to the formation of NETs. NETs are structures that help trap pathogens but may also promote autoimmune responses and excessive blood clotting.

With the current study, Dr Ebert and his colleagues examined whether NET formation could promote thrombosis in patients with MPNs.

The team found that neutrophils from MPN patients were more likely to form NETs than neutrophils from healthy individuals. However, incubating neutrophils with ruxolitinib reduced NET formation.

The researchers also found that mice with JAK2^V617F were more likely to form NETs and develop thrombosis when compared to wild-type mice. However, treatment with ruxolitinib reduced rates of thrombosis and prevented NET formation in the mice.

The researchers noted that expression of PAD4, a protein required for NET formation, is increased in JAK2^V617F-expressing neutrophils. And the team found that PAD4 is required for JAK2^V617F-driven NET formation and thrombosis in mouse models of MPNs.

Lastly, the researchers looked at data from 10,893 human subjects. None of these subjects had MPNs, but some had JAK2^V617F.

Subjects who were JAK2^V617F-positive had a significantly higher risk of thrombotic events than subjects without the mutation (P=0.0003).

Taken together, these findings suggest that JAK2 inhibition can reduce NET formation and ameliorate thrombosis in patients with MPNs or the JAK2^V617F mutation.

The researchers noted that, in the phase 3 RESPONSE trial, patients with polycythemia vera had a lower rate of thromboembolic events if they received ruxolitinib rather than standard therapy.

Image courtesy of AFIP

Preclinical research helps explain how the JAK1/2 inhibitor ruxolitinib can reduce thrombosis in patients with myeloproliferative neoplasms (MPNs).

Experiments revealed a link between JAK2^V617F and the formation of neutrophil extracellular traps (NETs), which have been implicated in thrombosis.

Researchers found that ruxolitinib reduced NET formation and decreased thrombosis in JAK2-mutant mice.

Benjamin L. Ebert, MD, PhD, of Brigham and Women’s Hospital in Boston, Massachusetts, and his colleagues reported these findings in Science Translational Medicine.

The researchers noted that patients with MPNs have an increased risk of thrombosis, and previous research linked thrombosis to the formation of NETs. NETs are structures that help trap pathogens but may also promote autoimmune responses and excessive blood clotting.

With the current study, Dr Ebert and his colleagues examined whether NET formation could promote thrombosis in patients with MPNs.

The team found that neutrophils from MPN patients were more likely to form NETs than neutrophils from healthy individuals. However, incubating neutrophils with ruxolitinib reduced NET formation.

The researchers also found that mice with JAK2^V617F were more likely to form NETs and develop thrombosis when compared to wild-type mice. However, treatment with ruxolitinib reduced rates of thrombosis and prevented NET formation in the mice.

The researchers noted that expression of PAD4, a protein required for NET formation, is increased in JAK2^V617F-expressing neutrophils. And the team found that PAD4 is required for JAK2^V617F-driven NET formation and thrombosis in mouse models of MPNs.

Lastly, the researchers looked at data from 10,893 human subjects. None of these subjects had MPNs, but some had JAK2^V617F.

Subjects who were JAK2^V617F-positive had a significantly higher risk of thrombotic events than subjects without the mutation (P=0.0003).

Taken together, these findings suggest that JAK2 inhibition can reduce NET formation and ameliorate thrombosis in patients with MPNs or the JAK2^V617F mutation.

The researchers noted that, in the phase 3 RESPONSE trial, patients with polycythemia vera had a lower rate of thromboembolic events if they received ruxolitinib rather than standard therapy.

Image courtesy of AFIP

Preclinical research helps explain how the JAK1/2 inhibitor ruxolitinib can reduce thrombosis in patients with myeloproliferative neoplasms (MPNs).

Experiments revealed a link between JAK2^V617F and the formation of neutrophil extracellular traps (NETs), which have been implicated in thrombosis.

Researchers found that ruxolitinib reduced NET formation and decreased thrombosis in JAK2-mutant mice.

Benjamin L. Ebert, MD, PhD, of Brigham and Women’s Hospital in Boston, Massachusetts, and his colleagues reported these findings in Science Translational Medicine.

The researchers noted that patients with MPNs have an increased risk of thrombosis, and previous research linked thrombosis to the formation of NETs. NETs are structures that help trap pathogens but may also promote autoimmune responses and excessive blood clotting.

With the current study, Dr Ebert and his colleagues examined whether NET formation could promote thrombosis in patients with MPNs.

The team found that neutrophils from MPN patients were more likely to form NETs than neutrophils from healthy individuals. However, incubating neutrophils with ruxolitinib reduced NET formation.

The researchers also found that mice with JAK2^V617F were more likely to form NETs and develop thrombosis when compared to wild-type mice. However, treatment with ruxolitinib reduced rates of thrombosis and prevented NET formation in the mice.

The researchers noted that expression of PAD4, a protein required for NET formation, is increased in JAK2^V617F-expressing neutrophils. And the team found that PAD4 is required for JAK2^V617F-driven NET formation and thrombosis in mouse models of MPNs.

Lastly, the researchers looked at data from 10,893 human subjects. None of these subjects had MPNs, but some had JAK2^V617F.

Subjects who were JAK2^V617F-positive had a significantly higher risk of thrombotic events than subjects without the mutation (P=0.0003).

Taken together, these findings suggest that JAK2 inhibition can reduce NET formation and ameliorate thrombosis in patients with MPNs or the JAK2^V617F mutation.

The researchers noted that, in the phase 3 RESPONSE trial, patients with polycythemia vera had a lower rate of thromboembolic events if they received ruxolitinib rather than standard therapy.

TORONTO – Almost half of adolescents (45%) reported that their primary care providers (PCPs) do not routinely ask them about sex, and only 13% report they’ve been offered screening for sexually transmitted infections (STIs), according to a survey study presented at the Pediatric Academic Societies meeting.

And it appears the teenagers aren’t even listening to much of what their parents are saying on the subject: The survey also found that 90% of parents reported that they talk to their adolescents about sex, but only 39% of adolescents reported the same.

Rawpixel/iStock/Getty Images

“I think that primary care physicians have a lot to cover when doing preventive health visits with adolescents, and talking about sex is not necessarily an easy or comfortable thing to do and so may be something that falls to a lower priority. And it certainly doesn’t help if parents are not supportive of the concept of confidential adolescent care,” Dr. Schneider related.

“We were very surprised to see that 25% of parents did not feel that PCPs should be discussing sex with their child. I think that we need to next work on getting the parents on board and building an expectation that adolescents, when visiting their PCP, will have confidential discussions about sexual health,” she said.

TORONTO – Almost half of adolescents (45%) reported that their primary care providers (PCPs) do not routinely ask them about sex, and only 13% report they’ve been offered screening for sexually transmitted infections (STIs), according to a survey study presented at the Pediatric Academic Societies meeting.

And it appears the teenagers aren’t even listening to much of what their parents are saying on the subject: The survey also found that 90% of parents reported that they talk to their adolescents about sex, but only 39% of adolescents reported the same.

Rawpixel/iStock/Getty Images

“I think that primary care physicians have a lot to cover when doing preventive health visits with adolescents, and talking about sex is not necessarily an easy or comfortable thing to do and so may be something that falls to a lower priority. And it certainly doesn’t help if parents are not supportive of the concept of confidential adolescent care,” Dr. Schneider related.

“We were very surprised to see that 25% of parents did not feel that PCPs should be discussing sex with their child. I think that we need to next work on getting the parents on board and building an expectation that adolescents, when visiting their PCP, will have confidential discussions about sexual health,” she said.

TORONTO – Almost half of adolescents (45%) reported that their primary care providers (PCPs) do not routinely ask them about sex, and only 13% report they’ve been offered screening for sexually transmitted infections (STIs), according to a survey study presented at the Pediatric Academic Societies meeting.

And it appears the teenagers aren’t even listening to much of what their parents are saying on the subject: The survey also found that 90% of parents reported that they talk to their adolescents about sex, but only 39% of adolescents reported the same.

Rawpixel/iStock/Getty Images

“I think that primary care physicians have a lot to cover when doing preventive health visits with adolescents, and talking about sex is not necessarily an easy or comfortable thing to do and so may be something that falls to a lower priority. And it certainly doesn’t help if parents are not supportive of the concept of confidential adolescent care,” Dr. Schneider related.

“We were very surprised to see that 25% of parents did not feel that PCPs should be discussing sex with their child. I think that we need to next work on getting the parents on board and building an expectation that adolescents, when visiting their PCP, will have confidential discussions about sexual health,” she said.

NEW YORK – Veterans are not a homogeneous group, and when treating them for posttraumatic stress, it helps to consider their specific cohort, according to Elspeth Cameron Ritchie, MD.

Veterans from the first Gulf War, for example, have lingering concerns regarding medical illness (Gulf War syndrome); those from Vietnam are aging and might have medical problems or find that while they did well while working, now they are experiencing PTSD symptoms for the first time; and those returning from the conflicts in Iraq and Afghanistan might have physical injuries from blasts – the “signature weapon” of those wars. Such blasts can cause amputations, genital injuries, head trauma, and PTSD, said Dr. Ritchie, of the Uniformed Services University of the Health Sciences, Bethesda, Md.

In this video interview, Dr. Ritchie discusses these and other issues related to the treatment of PTSD among veterans as presented during a workshop entitled “Psychiatry and U.S. Veterans,” which she chaired at the annual meeting of the American Psychiatric Association.

The workshop covered the spectrum of treatments that might be helpful for veterans.

“One thing I find with veterans is that they really want to have control over their treatment. They don’t want it to just be the doctor giving them a pill,” she said. “Veterans are resilient; they’re tough; they don’t like to be thought of as victims ... and when you’re working with them, it’s very important to link into that dynamic resilient piece and capitalize on their strengths.”

Dr. Ritchie reported having no disclosures.

[email protected]

SOURCE: Ritchie EC et al. APA Workshop.

NEW YORK – Veterans are not a homogeneous group, and when treating them for posttraumatic stress, it helps to consider their specific cohort, according to Elspeth Cameron Ritchie, MD.

Veterans from the first Gulf War, for example, have lingering concerns regarding medical illness (Gulf War syndrome); those from Vietnam are aging and might have medical problems or find that while they did well while working, now they are experiencing PTSD symptoms for the first time; and those returning from the conflicts in Iraq and Afghanistan might have physical injuries from blasts – the “signature weapon” of those wars. Such blasts can cause amputations, genital injuries, head trauma, and PTSD, said Dr. Ritchie, of the Uniformed Services University of the Health Sciences, Bethesda, Md.

In this video interview, Dr. Ritchie discusses these and other issues related to the treatment of PTSD among veterans as presented during a workshop entitled “Psychiatry and U.S. Veterans,” which she chaired at the annual meeting of the American Psychiatric Association.

The workshop covered the spectrum of treatments that might be helpful for veterans.

“One thing I find with veterans is that they really want to have control over their treatment. They don’t want it to just be the doctor giving them a pill,” she said. “Veterans are resilient; they’re tough; they don’t like to be thought of as victims ... and when you’re working with them, it’s very important to link into that dynamic resilient piece and capitalize on their strengths.”

Dr. Ritchie reported having no disclosures.

[email protected]

SOURCE: Ritchie EC et al. APA Workshop.

NEW YORK – Veterans are not a homogeneous group, and when treating them for posttraumatic stress, it helps to consider their specific cohort, according to Elspeth Cameron Ritchie, MD.

Veterans from the first Gulf War, for example, have lingering concerns regarding medical illness (Gulf War syndrome); those from Vietnam are aging and might have medical problems or find that while they did well while working, now they are experiencing PTSD symptoms for the first time; and those returning from the conflicts in Iraq and Afghanistan might have physical injuries from blasts – the “signature weapon” of those wars. Such blasts can cause amputations, genital injuries, head trauma, and PTSD, said Dr. Ritchie, of the Uniformed Services University of the Health Sciences, Bethesda, Md.

In this video interview, Dr. Ritchie discusses these and other issues related to the treatment of PTSD among veterans as presented during a workshop entitled “Psychiatry and U.S. Veterans,” which she chaired at the annual meeting of the American Psychiatric Association.

The workshop covered the spectrum of treatments that might be helpful for veterans.

“One thing I find with veterans is that they really want to have control over their treatment. They don’t want it to just be the doctor giving them a pill,” she said. “Veterans are resilient; they’re tough; they don’t like to be thought of as victims ... and when you’re working with them, it’s very important to link into that dynamic resilient piece and capitalize on their strengths.”

Dr. Ritchie reported having no disclosures.

[email protected]

SOURCE: Ritchie EC et al. APA Workshop.

Ivacaftor, a therapy that targets the G551D CFTR gene mutation to treat cystic fibrosis, significantly reduced hospital admission rates in patients with cystic fibrosis with a variety of mutations, according to results published May 7 in Health Affairs.

The study involved 143 patients being treated with ivacaftor between February 2012 and February 2015. In 2014, the FDA expanded its approval for the use of ivacaftor by cystic fibrosis patients to include nine additional mutations, and patients with these mutations were included in this study.

copyright Zerbor/Thinkstock

SOURCE: Feng LB et al. Health Aff. 2018 May 8. doi: 10.1377/hlthaff.2017.1554

Ivacaftor, a therapy that targets the G551D CFTR gene mutation to treat cystic fibrosis, significantly reduced hospital admission rates in patients with cystic fibrosis with a variety of mutations, according to results published May 7 in Health Affairs.

The study involved 143 patients being treated with ivacaftor between February 2012 and February 2015. In 2014, the FDA expanded its approval for the use of ivacaftor by cystic fibrosis patients to include nine additional mutations, and patients with these mutations were included in this study.

copyright Zerbor/Thinkstock

SOURCE: Feng LB et al. Health Aff. 2018 May 8. doi: 10.1377/hlthaff.2017.1554

Ivacaftor, a therapy that targets the G551D CFTR gene mutation to treat cystic fibrosis, significantly reduced hospital admission rates in patients with cystic fibrosis with a variety of mutations, according to results published May 7 in Health Affairs.

The study involved 143 patients being treated with ivacaftor between February 2012 and February 2015. In 2014, the FDA expanded its approval for the use of ivacaftor by cystic fibrosis patients to include nine additional mutations, and patients with these mutations were included in this study.

copyright Zerbor/Thinkstock

SOURCE: Feng LB et al. Health Aff. 2018 May 8. doi: 10.1377/hlthaff.2017.1554

The HOPE in Action Multicenter Kidney Study, the first large-scale clinical trial to study kidney transplantations between people with HIV, has begun at clinical centers across the United States, according to an announcement by the National Institutes of Health. The study, sponsored by the National Institute of Allergy and Infectious Diseases and NIH, will assess the safety of HIV-positive donor to HIV-positive recipient kidney transplantation. This form of transplantation was made legal by the passage of the HOPE (HIV Organ Policy Equity) Act, which permits the transplantation of organs from donors with HIV into qualified HIV-positive recipients with end-stage organ failure.

London_England/Thinkstock

Outcomes to be studied in the multicenter trial will include potential transplant-related and HIV-related complications following surgery, as well as organ rejection, organ failure, and failure of previously effective HIV medications. The study is currently enrolling and is expected to include 360 participants, with an estimated completion date of Aug. 1, 2022.

“The HOPE Act of 2013 opened the door for researchers to explore a potential new source of donor organs for those living with HIV – a population with a significant and growing need for transplants. This study offers a chance to improve the health of those living with HIV, and increase the overall supply of transplantable organs,” said NIAID Director Anthony S. Fauci, MD, in the NIH news release. Transplantation of organs from HIV-positive donors to HIV-negative recipients remains illegal in the United States.

More information about the study can be found at ClinicalTrials.gov using the identifier NCT03500315. A similar trial to examine liver transplantation, the HOPE in Action Multicenter Liver Study, is expected to launch later in 2018.

[email protected]

The HOPE in Action Multicenter Kidney Study, the first large-scale clinical trial to study kidney transplantations between people with HIV, has begun at clinical centers across the United States, according to an announcement by the National Institutes of Health. The study, sponsored by the National Institute of Allergy and Infectious Diseases and NIH, will assess the safety of HIV-positive donor to HIV-positive recipient kidney transplantation. This form of transplantation was made legal by the passage of the HOPE (HIV Organ Policy Equity) Act, which permits the transplantation of organs from donors with HIV into qualified HIV-positive recipients with end-stage organ failure.

London_England/Thinkstock

Outcomes to be studied in the multicenter trial will include potential transplant-related and HIV-related complications following surgery, as well as organ rejection, organ failure, and failure of previously effective HIV medications. The study is currently enrolling and is expected to include 360 participants, with an estimated completion date of Aug. 1, 2022.

“The HOPE Act of 2013 opened the door for researchers to explore a potential new source of donor organs for those living with HIV – a population with a significant and growing need for transplants. This study offers a chance to improve the health of those living with HIV, and increase the overall supply of transplantable organs,” said NIAID Director Anthony S. Fauci, MD, in the NIH news release. Transplantation of organs from HIV-positive donors to HIV-negative recipients remains illegal in the United States.

More information about the study can be found at ClinicalTrials.gov using the identifier NCT03500315. A similar trial to examine liver transplantation, the HOPE in Action Multicenter Liver Study, is expected to launch later in 2018.

[email protected]

The HOPE in Action Multicenter Kidney Study, the first large-scale clinical trial to study kidney transplantations between people with HIV, has begun at clinical centers across the United States, according to an announcement by the National Institutes of Health. The study, sponsored by the National Institute of Allergy and Infectious Diseases and NIH, will assess the safety of HIV-positive donor to HIV-positive recipient kidney transplantation. This form of transplantation was made legal by the passage of the HOPE (HIV Organ Policy Equity) Act, which permits the transplantation of organs from donors with HIV into qualified HIV-positive recipients with end-stage organ failure.

London_England/Thinkstock

Outcomes to be studied in the multicenter trial will include potential transplant-related and HIV-related complications following surgery, as well as organ rejection, organ failure, and failure of previously effective HIV medications. The study is currently enrolling and is expected to include 360 participants, with an estimated completion date of Aug. 1, 2022.

“The HOPE Act of 2013 opened the door for researchers to explore a potential new source of donor organs for those living with HIV – a population with a significant and growing need for transplants. This study offers a chance to improve the health of those living with HIV, and increase the overall supply of transplantable organs,” said NIAID Director Anthony S. Fauci, MD, in the NIH news release. Transplantation of organs from HIV-positive donors to HIV-negative recipients remains illegal in the United States.

More information about the study can be found at ClinicalTrials.gov using the identifier NCT03500315. A similar trial to examine liver transplantation, the HOPE in Action Multicenter Liver Study, is expected to launch later in 2018.

[email protected]

Current clinical trials evaluating combination therapy for pulmonary artery hypertension (PAH) may be longer than what is needed to demonstrate treatment benefit, results of a recent meta-analysis suggest.

In PAH trials of combination therapy, the absolute risk reduction of clinical worsening beyond 6-12 months was relatively constant, according to results of the study published in the May issue of the journal Chest^®.

Rawpixel/iStock/Getty Images

Pragmatically, these results raise the possibility that PAH combination therapy trials could be shorter in duration. Some recent event-driven studies have lasted up to 6 years, with patients on treatment for about 2 of those years, investigators noted.

“In the context of an orphan disease with limited and competing recruitment for trials and the rapidly changing treatment paradigm in PAH, the optimal duration of future trials should be revisited,” Dr. Lajoie and her colleagues wrote in a discussion of their findings.

They also cautioned that NNT, a measure of how many patient treatments are needed to prevent one additional adverse event, could be “misleading” despite its value as a simple measure of treatment impact.

Likewise, relative risk can be misleading; for example, a treatment reducing event risk from 30% to 20% represents a relative risk reduction of approximately 35%, but so does a treatment reducing event risk from 3% to 2%, the researchers noted.

“Multiple factors, in addition to the efficacy of the therapy and the comparator, may directly influence the NNT and relative risk and should be taken into account in their interpretation,” they said in their report.

Dr. Lajoie had no disclosures related to the study. Her coauthors had disclosures related to Actelion Pharmaceuticals, Bayer, and GlaxoSmithKline, among others.

SOURCE: Lajoie AC et al. Chest. 2017 May;153(5):1142-52.

Current clinical trials evaluating combination therapy for pulmonary artery hypertension (PAH) may be longer than what is needed to demonstrate treatment benefit, results of a recent meta-analysis suggest.

In PAH trials of combination therapy, the absolute risk reduction of clinical worsening beyond 6-12 months was relatively constant, according to results of the study published in the May issue of the journal Chest^®.

Rawpixel/iStock/Getty Images

Pragmatically, these results raise the possibility that PAH combination therapy trials could be shorter in duration. Some recent event-driven studies have lasted up to 6 years, with patients on treatment for about 2 of those years, investigators noted.

“In the context of an orphan disease with limited and competing recruitment for trials and the rapidly changing treatment paradigm in PAH, the optimal duration of future trials should be revisited,” Dr. Lajoie and her colleagues wrote in a discussion of their findings.

They also cautioned that NNT, a measure of how many patient treatments are needed to prevent one additional adverse event, could be “misleading” despite its value as a simple measure of treatment impact.

Likewise, relative risk can be misleading; for example, a treatment reducing event risk from 30% to 20% represents a relative risk reduction of approximately 35%, but so does a treatment reducing event risk from 3% to 2%, the researchers noted.

“Multiple factors, in addition to the efficacy of the therapy and the comparator, may directly influence the NNT and relative risk and should be taken into account in their interpretation,” they said in their report.

Dr. Lajoie had no disclosures related to the study. Her coauthors had disclosures related to Actelion Pharmaceuticals, Bayer, and GlaxoSmithKline, among others.

SOURCE: Lajoie AC et al. Chest. 2017 May;153(5):1142-52.

Current clinical trials evaluating combination therapy for pulmonary artery hypertension (PAH) may be longer than what is needed to demonstrate treatment benefit, results of a recent meta-analysis suggest.

In PAH trials of combination therapy, the absolute risk reduction of clinical worsening beyond 6-12 months was relatively constant, according to results of the study published in the May issue of the journal Chest^®.

Rawpixel/iStock/Getty Images

Pragmatically, these results raise the possibility that PAH combination therapy trials could be shorter in duration. Some recent event-driven studies have lasted up to 6 years, with patients on treatment for about 2 of those years, investigators noted.

“In the context of an orphan disease with limited and competing recruitment for trials and the rapidly changing treatment paradigm in PAH, the optimal duration of future trials should be revisited,” Dr. Lajoie and her colleagues wrote in a discussion of their findings.

They also cautioned that NNT, a measure of how many patient treatments are needed to prevent one additional adverse event, could be “misleading” despite its value as a simple measure of treatment impact.

Likewise, relative risk can be misleading; for example, a treatment reducing event risk from 30% to 20% represents a relative risk reduction of approximately 35%, but so does a treatment reducing event risk from 3% to 2%, the researchers noted.

“Multiple factors, in addition to the efficacy of the therapy and the comparator, may directly influence the NNT and relative risk and should be taken into account in their interpretation,” they said in their report.

Dr. Lajoie had no disclosures related to the study. Her coauthors had disclosures related to Actelion Pharmaceuticals, Bayer, and GlaxoSmithKline, among others.

SOURCE: Lajoie AC et al. Chest. 2017 May;153(5):1142-52.

NEW ORLEANS – If a patient’s asthma symptoms don’t fluctuate over time and in severity, it’s definitely time to entertain the possibility of diagnostic error, Kyle I. Happel, MD, said at the annual meeting of the American College of Physicians.

“Asthma is a disease whose symptoms are caused by variable airflow obstruction. It varies throughout the day, usually, and certainly by the week or by the month. I want you to think about the variability of a patient’s disease symptoms in forming your index of suspicion for this disease,” urged Dr. Happel, of the section of pulmonary, critical care, and allergy/immunology at Louisiana State University Medical Center in New Orleans.

Bruce Jancin/MDedge News

[email protected]

NEW ORLEANS – If a patient’s asthma symptoms don’t fluctuate over time and in severity, it’s definitely time to entertain the possibility of diagnostic error, Kyle I. Happel, MD, said at the annual meeting of the American College of Physicians.

“Asthma is a disease whose symptoms are caused by variable airflow obstruction. It varies throughout the day, usually, and certainly by the week or by the month. I want you to think about the variability of a patient’s disease symptoms in forming your index of suspicion for this disease,” urged Dr. Happel, of the section of pulmonary, critical care, and allergy/immunology at Louisiana State University Medical Center in New Orleans.

Bruce Jancin/MDedge News

[email protected]

NEW ORLEANS – If a patient’s asthma symptoms don’t fluctuate over time and in severity, it’s definitely time to entertain the possibility of diagnostic error, Kyle I. Happel, MD, said at the annual meeting of the American College of Physicians.

“Asthma is a disease whose symptoms are caused by variable airflow obstruction. It varies throughout the day, usually, and certainly by the week or by the month. I want you to think about the variability of a patient’s disease symptoms in forming your index of suspicion for this disease,” urged Dr. Happel, of the section of pulmonary, critical care, and allergy/immunology at Louisiana State University Medical Center in New Orleans.

Bruce Jancin/MDedge News

[email protected]