User login
Children exposed to violence show accelerated cellular aging
SAN FRANCISCO – Children exposed to high levels of urban violence demonstrate accelerated cellular aging beyond their chronologic years, Vasiliki Michopoulos, PhD, reported at the annual conference of the Anxiety and Depression Association of America.
This fast-running cellular biologic clock is not a good thing. Neither is their blunted heart rate variability in response to stress, an indicator of autonomic dysfunction that constitutes a cardiovascular risk factor, she added.
Accelerated cellular aging as measured by DNA methylation in blood or saliva samples has become a red hot research area. Investigators have shown that a person’s DNA methylation age, also known as epigenetic age, predicts all-cause mortality risk in later life. In adults, accelerated cellular aging as reflected in a 5-year discrepancy between DNA methylation age and chronologic age is predictive of an adjusted 16% increased mortality risk independent of social class, education level, lifestyle factors, and chronic diseases, including diabetes and cardiovascular disease (Genome Biol. 2015 Jan 30;16:25).
Lifetime exposure to stress has been convincingly shown to accelerate epigenetic aging, as reflected by DNA methylation level. But, prior to Dr. Michopoulos’s study, it wasn’t known if exposure to violence during childhood influences epigenetic aging or if perhaps only later-life trauma is relevant.
To address this question, she and her coinvestigators recruited 101 African American children aged 6-11 years and their mothers. Of note, medical attention wasn’t being sought for the children. Rather, their mothers were approached regarding study participation while attending primary care clinics at Atlanta’s Grady Memorial Hospital. Children were not eligible to participate if they had been diagnosed with autism spectrum disorder, bipolar disorder, cognitive impairment, or a psychotic disorder.
The children had been exposed to a lot of violence, both witnessed and directly experienced, as reflected in their mean total score of 18.9 on the Violence Exposure Scale for Children-Revised (VEX-R). More than 80% of the children had witnessed an assault and 30% a murder. Stabbings, shootings, drug trafficking, and arrests were other common exposures.
One-quarter of the children showed accelerated cellular aging. They had experienced twice as much violence exposure as reflected in their VEX-R scores, compared with children whose epigenetic and chronologic ages were the same.
The children with accelerated cellular aging also demonstrated decreased heart rate variability in response to a standardized stressor, which involved a startle experience in a darkened room. Their heart rate in the stressor situation shot up on average by 17 bpm less than the children whose cellular age as measured by DNA methylation matched their chronologic age.
“Our data suggest that DNA methylation may serve as a biomarker by which to identify at-risk individuals who may benefit from interventions that decrease risk for cardiometabolic disorders in adulthood,” Dr. Michopoulos said. “It’ll be really interesting to see, as these kids grow up and develop, whether their phenotype stays static, reverses, or changes completely.”
Dr. Michopoulos reported having no financial conflicts regarding the study, conducted as part of the Grady Trauma Project (www.gradytraumaproject.com) with funding from the National Institute of Mental Health and Emory University and Grady Memorial Hospital, both in Atlanta.
SAN FRANCISCO – Children exposed to high levels of urban violence demonstrate accelerated cellular aging beyond their chronologic years, Vasiliki Michopoulos, PhD, reported at the annual conference of the Anxiety and Depression Association of America.
This fast-running cellular biologic clock is not a good thing. Neither is their blunted heart rate variability in response to stress, an indicator of autonomic dysfunction that constitutes a cardiovascular risk factor, she added.
Accelerated cellular aging as measured by DNA methylation in blood or saliva samples has become a red hot research area. Investigators have shown that a person’s DNA methylation age, also known as epigenetic age, predicts all-cause mortality risk in later life. In adults, accelerated cellular aging as reflected in a 5-year discrepancy between DNA methylation age and chronologic age is predictive of an adjusted 16% increased mortality risk independent of social class, education level, lifestyle factors, and chronic diseases, including diabetes and cardiovascular disease (Genome Biol. 2015 Jan 30;16:25).
Lifetime exposure to stress has been convincingly shown to accelerate epigenetic aging, as reflected by DNA methylation level. But, prior to Dr. Michopoulos’s study, it wasn’t known if exposure to violence during childhood influences epigenetic aging or if perhaps only later-life trauma is relevant.
To address this question, she and her coinvestigators recruited 101 African American children aged 6-11 years and their mothers. Of note, medical attention wasn’t being sought for the children. Rather, their mothers were approached regarding study participation while attending primary care clinics at Atlanta’s Grady Memorial Hospital. Children were not eligible to participate if they had been diagnosed with autism spectrum disorder, bipolar disorder, cognitive impairment, or a psychotic disorder.
The children had been exposed to a lot of violence, both witnessed and directly experienced, as reflected in their mean total score of 18.9 on the Violence Exposure Scale for Children-Revised (VEX-R). More than 80% of the children had witnessed an assault and 30% a murder. Stabbings, shootings, drug trafficking, and arrests were other common exposures.
One-quarter of the children showed accelerated cellular aging. They had experienced twice as much violence exposure as reflected in their VEX-R scores, compared with children whose epigenetic and chronologic ages were the same.
The children with accelerated cellular aging also demonstrated decreased heart rate variability in response to a standardized stressor, which involved a startle experience in a darkened room. Their heart rate in the stressor situation shot up on average by 17 bpm less than the children whose cellular age as measured by DNA methylation matched their chronologic age.
“Our data suggest that DNA methylation may serve as a biomarker by which to identify at-risk individuals who may benefit from interventions that decrease risk for cardiometabolic disorders in adulthood,” Dr. Michopoulos said. “It’ll be really interesting to see, as these kids grow up and develop, whether their phenotype stays static, reverses, or changes completely.”
Dr. Michopoulos reported having no financial conflicts regarding the study, conducted as part of the Grady Trauma Project (www.gradytraumaproject.com) with funding from the National Institute of Mental Health and Emory University and Grady Memorial Hospital, both in Atlanta.
SAN FRANCISCO – Children exposed to high levels of urban violence demonstrate accelerated cellular aging beyond their chronologic years, Vasiliki Michopoulos, PhD, reported at the annual conference of the Anxiety and Depression Association of America.
This fast-running cellular biologic clock is not a good thing. Neither is their blunted heart rate variability in response to stress, an indicator of autonomic dysfunction that constitutes a cardiovascular risk factor, she added.
Accelerated cellular aging as measured by DNA methylation in blood or saliva samples has become a red hot research area. Investigators have shown that a person’s DNA methylation age, also known as epigenetic age, predicts all-cause mortality risk in later life. In adults, accelerated cellular aging as reflected in a 5-year discrepancy between DNA methylation age and chronologic age is predictive of an adjusted 16% increased mortality risk independent of social class, education level, lifestyle factors, and chronic diseases, including diabetes and cardiovascular disease (Genome Biol. 2015 Jan 30;16:25).
Lifetime exposure to stress has been convincingly shown to accelerate epigenetic aging, as reflected by DNA methylation level. But, prior to Dr. Michopoulos’s study, it wasn’t known if exposure to violence during childhood influences epigenetic aging or if perhaps only later-life trauma is relevant.
To address this question, she and her coinvestigators recruited 101 African American children aged 6-11 years and their mothers. Of note, medical attention wasn’t being sought for the children. Rather, their mothers were approached regarding study participation while attending primary care clinics at Atlanta’s Grady Memorial Hospital. Children were not eligible to participate if they had been diagnosed with autism spectrum disorder, bipolar disorder, cognitive impairment, or a psychotic disorder.
The children had been exposed to a lot of violence, both witnessed and directly experienced, as reflected in their mean total score of 18.9 on the Violence Exposure Scale for Children-Revised (VEX-R). More than 80% of the children had witnessed an assault and 30% a murder. Stabbings, shootings, drug trafficking, and arrests were other common exposures.
One-quarter of the children showed accelerated cellular aging. They had experienced twice as much violence exposure as reflected in their VEX-R scores, compared with children whose epigenetic and chronologic ages were the same.
The children with accelerated cellular aging also demonstrated decreased heart rate variability in response to a standardized stressor, which involved a startle experience in a darkened room. Their heart rate in the stressor situation shot up on average by 17 bpm less than the children whose cellular age as measured by DNA methylation matched their chronologic age.
“Our data suggest that DNA methylation may serve as a biomarker by which to identify at-risk individuals who may benefit from interventions that decrease risk for cardiometabolic disorders in adulthood,” Dr. Michopoulos said. “It’ll be really interesting to see, as these kids grow up and develop, whether their phenotype stays static, reverses, or changes completely.”
Dr. Michopoulos reported having no financial conflicts regarding the study, conducted as part of the Grady Trauma Project (www.gradytraumaproject.com) with funding from the National Institute of Mental Health and Emory University and Grady Memorial Hospital, both in Atlanta.
AT THE ANXIETY AND DEPRESSION CONFERENCE 2017
Key clinical point:
Major finding: Children who demonstrated advanced cellular aging based on DNA methylation levels had experienced twice as much exposure to violence as those whose epigenetic and chronologic ages matched.
Data source: This cross-sectional study included 101 urban African American children aged 6-11 years.
Disclosures: The presenter reported having no financial conflicts regarding the study, which was funded by the National Institute of Mental Health and Emory University and Grady Memorial Hospital, both in Atlanta.
Intensive BP lowering may reduce larger hematoma expansion in ICH
BOSTON – Intensive systolic blood pressure reduction did not significantly reduce hematoma expansion, compared with standard systolic blood pressure reduction in the Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) II trial, but, in a post hoc analysis, it did show a strong trend toward reducing hematoma expansion in those with a larger initial hematoma volume.
In 450 patients randomized to receive intensive treatment and 426 randomized to receive standard treatment in the large, international, phase III randomized trial, the proportion of patients with any hematoma expansion was 46.4% and 52.3% , respectively (relative risk, 0.89; 95% confidence interval, 0.73-1.07). The proportion with hematoma expansion with an increase of greater than 33% was 18.9% and 24.4%, respectively (RR, 0.77; 95% CI, 0.58-1.03), Joshua N. Goldstein, MD, reported at the annual meeting of the American Academy of Neurology.
The confidence intervals suggested only a trend toward improvement, as the difference between the groups did not reach statistical significance, he said.
To determine if intensive systolic blood pressure reduction might have more of an impact among higher-risk patients, the investigators conducted a post hoc, secondary analysis in those with relatively larger hematomas. Among patients with an initial hematoma volume of at least 10 mL (at least half of the study population had smaller hematomas), the proportion with any hematoma expansion was 53.8% in the intensive treatment group and 61.3% in the standard treatment group (RR, 0.88; 95% CI, 0.67-1.13), and the proportion of patients with hematoma expansion of greater than 33% was 18% and 27.6%, respectively (RR, 0.67; 95% CI, 0.45-1.00), said Dr. Goldstein of Massachusetts General Hospital, Boston.
In those with an expansion greater than 33% and a hematoma volume of at least 6 cc, the finding was similar.
“The trend looks a little bit more aggressive,” he said, but the 95% confidence interval in those with larger hematomas reached 1.
Study subjects had elevated blood pressure at arrival, a Glasgow coma scale score of at least 5, and a hematoma volume of less than 60 cc. They were enrolled and randomized within 4.5 hours of symptom onset. Those in the intensive treatment group were treated with a goal of achieving between 110 and 139 mm Hg within 24 hours, and those in the standard treatment group were treated with a goal of achieving between 140 mm Hg and 179 mm Hg within 24 hours. They underwent baseline and 24-hour computed tomography scans, which were analyzed centrally by blinded investigators who recorded any increase of 0.5 mL or more, an increase of more than 33% , an increase of more than 33% or more than 6 mL, and an intraventricular hemorrhage volume greater than 2 mL.
These measures were correlated with death and disability, and hematoma enlargement was shown to be significantly associated with those outcomes at 3 months after randomization (RR, 1.59; 95% CI, 1.25-2.02), Dr. Goldstein said.
Previous studies have suggested that intensive lowering of systolic BP in patients with intracerebral hemorrhage can reduce the rate of hematoma expansion. As such, the hypothesis of the current study was that the intensive treatment of elevated blood pressures – arriving systolic blood pressure of greater than 180 mm Hg – would reduce the likelihood of death and disability at 3 months, Dr. Goldstein said,
The question is whether the biomarker – hematoma expansion – is really linked to clinical outcome, he said, “because a lot of our attempts to treat hematoma expansion are based on the assumption that, if we reduce hematoma expansion, we’re going to improve clinical outcomes.”
“In this trial ... the expanders had more death and disability than nonexpanders, and this was statistically significant, so hematoma expansion does seem to be a statistically significant predictor of poor outcome,” he said.
Thus, the strong trend toward a reduced risk of hematoma expansion with intensive blood pressure lowering in patients with larger hematoma volumes at baseline in this analysis is noteworthy, he said.
“It appears that the treatment is affecting the biomarker, that the treatment is affecting hematoma expansion ... and hematoma expansion was a significant predictor of death and disability ... so why didn’t we get the result we wanted from the trial?” he asked.
It may be that a greater magnitude of reduction in the risk of hematoma expansion was necessary, he said.
“In other words, even if our treatment is having an effect, it’s just not having a big enough effect to change outcomes,” he said, adding that future trials probably need to involve a much bigger impact on the risk of expansion to translate to a change in clinical outcomes.”
This study was sponsored by the National Institute of Neurological Disorders and Stroke. Dr. Goldstein reported having no disclosures.
BOSTON – Intensive systolic blood pressure reduction did not significantly reduce hematoma expansion, compared with standard systolic blood pressure reduction in the Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) II trial, but, in a post hoc analysis, it did show a strong trend toward reducing hematoma expansion in those with a larger initial hematoma volume.
In 450 patients randomized to receive intensive treatment and 426 randomized to receive standard treatment in the large, international, phase III randomized trial, the proportion of patients with any hematoma expansion was 46.4% and 52.3% , respectively (relative risk, 0.89; 95% confidence interval, 0.73-1.07). The proportion with hematoma expansion with an increase of greater than 33% was 18.9% and 24.4%, respectively (RR, 0.77; 95% CI, 0.58-1.03), Joshua N. Goldstein, MD, reported at the annual meeting of the American Academy of Neurology.
The confidence intervals suggested only a trend toward improvement, as the difference between the groups did not reach statistical significance, he said.
To determine if intensive systolic blood pressure reduction might have more of an impact among higher-risk patients, the investigators conducted a post hoc, secondary analysis in those with relatively larger hematomas. Among patients with an initial hematoma volume of at least 10 mL (at least half of the study population had smaller hematomas), the proportion with any hematoma expansion was 53.8% in the intensive treatment group and 61.3% in the standard treatment group (RR, 0.88; 95% CI, 0.67-1.13), and the proportion of patients with hematoma expansion of greater than 33% was 18% and 27.6%, respectively (RR, 0.67; 95% CI, 0.45-1.00), said Dr. Goldstein of Massachusetts General Hospital, Boston.
In those with an expansion greater than 33% and a hematoma volume of at least 6 cc, the finding was similar.
“The trend looks a little bit more aggressive,” he said, but the 95% confidence interval in those with larger hematomas reached 1.
Study subjects had elevated blood pressure at arrival, a Glasgow coma scale score of at least 5, and a hematoma volume of less than 60 cc. They were enrolled and randomized within 4.5 hours of symptom onset. Those in the intensive treatment group were treated with a goal of achieving between 110 and 139 mm Hg within 24 hours, and those in the standard treatment group were treated with a goal of achieving between 140 mm Hg and 179 mm Hg within 24 hours. They underwent baseline and 24-hour computed tomography scans, which were analyzed centrally by blinded investigators who recorded any increase of 0.5 mL or more, an increase of more than 33% , an increase of more than 33% or more than 6 mL, and an intraventricular hemorrhage volume greater than 2 mL.
These measures were correlated with death and disability, and hematoma enlargement was shown to be significantly associated with those outcomes at 3 months after randomization (RR, 1.59; 95% CI, 1.25-2.02), Dr. Goldstein said.
Previous studies have suggested that intensive lowering of systolic BP in patients with intracerebral hemorrhage can reduce the rate of hematoma expansion. As such, the hypothesis of the current study was that the intensive treatment of elevated blood pressures – arriving systolic blood pressure of greater than 180 mm Hg – would reduce the likelihood of death and disability at 3 months, Dr. Goldstein said,
The question is whether the biomarker – hematoma expansion – is really linked to clinical outcome, he said, “because a lot of our attempts to treat hematoma expansion are based on the assumption that, if we reduce hematoma expansion, we’re going to improve clinical outcomes.”
“In this trial ... the expanders had more death and disability than nonexpanders, and this was statistically significant, so hematoma expansion does seem to be a statistically significant predictor of poor outcome,” he said.
Thus, the strong trend toward a reduced risk of hematoma expansion with intensive blood pressure lowering in patients with larger hematoma volumes at baseline in this analysis is noteworthy, he said.
“It appears that the treatment is affecting the biomarker, that the treatment is affecting hematoma expansion ... and hematoma expansion was a significant predictor of death and disability ... so why didn’t we get the result we wanted from the trial?” he asked.
It may be that a greater magnitude of reduction in the risk of hematoma expansion was necessary, he said.
“In other words, even if our treatment is having an effect, it’s just not having a big enough effect to change outcomes,” he said, adding that future trials probably need to involve a much bigger impact on the risk of expansion to translate to a change in clinical outcomes.”
This study was sponsored by the National Institute of Neurological Disorders and Stroke. Dr. Goldstein reported having no disclosures.
BOSTON – Intensive systolic blood pressure reduction did not significantly reduce hematoma expansion, compared with standard systolic blood pressure reduction in the Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) II trial, but, in a post hoc analysis, it did show a strong trend toward reducing hematoma expansion in those with a larger initial hematoma volume.
In 450 patients randomized to receive intensive treatment and 426 randomized to receive standard treatment in the large, international, phase III randomized trial, the proportion of patients with any hematoma expansion was 46.4% and 52.3% , respectively (relative risk, 0.89; 95% confidence interval, 0.73-1.07). The proportion with hematoma expansion with an increase of greater than 33% was 18.9% and 24.4%, respectively (RR, 0.77; 95% CI, 0.58-1.03), Joshua N. Goldstein, MD, reported at the annual meeting of the American Academy of Neurology.
The confidence intervals suggested only a trend toward improvement, as the difference between the groups did not reach statistical significance, he said.
To determine if intensive systolic blood pressure reduction might have more of an impact among higher-risk patients, the investigators conducted a post hoc, secondary analysis in those with relatively larger hematomas. Among patients with an initial hematoma volume of at least 10 mL (at least half of the study population had smaller hematomas), the proportion with any hematoma expansion was 53.8% in the intensive treatment group and 61.3% in the standard treatment group (RR, 0.88; 95% CI, 0.67-1.13), and the proportion of patients with hematoma expansion of greater than 33% was 18% and 27.6%, respectively (RR, 0.67; 95% CI, 0.45-1.00), said Dr. Goldstein of Massachusetts General Hospital, Boston.
In those with an expansion greater than 33% and a hematoma volume of at least 6 cc, the finding was similar.
“The trend looks a little bit more aggressive,” he said, but the 95% confidence interval in those with larger hematomas reached 1.
Study subjects had elevated blood pressure at arrival, a Glasgow coma scale score of at least 5, and a hematoma volume of less than 60 cc. They were enrolled and randomized within 4.5 hours of symptom onset. Those in the intensive treatment group were treated with a goal of achieving between 110 and 139 mm Hg within 24 hours, and those in the standard treatment group were treated with a goal of achieving between 140 mm Hg and 179 mm Hg within 24 hours. They underwent baseline and 24-hour computed tomography scans, which were analyzed centrally by blinded investigators who recorded any increase of 0.5 mL or more, an increase of more than 33% , an increase of more than 33% or more than 6 mL, and an intraventricular hemorrhage volume greater than 2 mL.
These measures were correlated with death and disability, and hematoma enlargement was shown to be significantly associated with those outcomes at 3 months after randomization (RR, 1.59; 95% CI, 1.25-2.02), Dr. Goldstein said.
Previous studies have suggested that intensive lowering of systolic BP in patients with intracerebral hemorrhage can reduce the rate of hematoma expansion. As such, the hypothesis of the current study was that the intensive treatment of elevated blood pressures – arriving systolic blood pressure of greater than 180 mm Hg – would reduce the likelihood of death and disability at 3 months, Dr. Goldstein said,
The question is whether the biomarker – hematoma expansion – is really linked to clinical outcome, he said, “because a lot of our attempts to treat hematoma expansion are based on the assumption that, if we reduce hematoma expansion, we’re going to improve clinical outcomes.”
“In this trial ... the expanders had more death and disability than nonexpanders, and this was statistically significant, so hematoma expansion does seem to be a statistically significant predictor of poor outcome,” he said.
Thus, the strong trend toward a reduced risk of hematoma expansion with intensive blood pressure lowering in patients with larger hematoma volumes at baseline in this analysis is noteworthy, he said.
“It appears that the treatment is affecting the biomarker, that the treatment is affecting hematoma expansion ... and hematoma expansion was a significant predictor of death and disability ... so why didn’t we get the result we wanted from the trial?” he asked.
It may be that a greater magnitude of reduction in the risk of hematoma expansion was necessary, he said.
“In other words, even if our treatment is having an effect, it’s just not having a big enough effect to change outcomes,” he said, adding that future trials probably need to involve a much bigger impact on the risk of expansion to translate to a change in clinical outcomes.”
This study was sponsored by the National Institute of Neurological Disorders and Stroke. Dr. Goldstein reported having no disclosures.
Key clinical point:
Major finding: Among patients with larger initial hematoma volume, expansion greater than 33% occurred in 18% vs. 28% in those with intense vs. standard blood pressure lowering, respectively (RR, 0.67).
Data source: The randomized phase III ATACH II trial involving 876 patients.
Disclosures: This study was sponsored by the National Institute of Neurological Disorders and Stroke. Dr. Goldstein reported having no disclosures.
Health care reform survey: What would make a difference for you?
[polldaddy:{"method":"iframe","type":"survey","src":"//clinicalpolls.polldaddy.com/s/health-care-reform-survey-what-would-make-a-difference-for-you?iframe=1"}]
[polldaddy:{"method":"iframe","type":"survey","src":"//clinicalpolls.polldaddy.com/s/health-care-reform-survey-what-would-make-a-difference-for-you?iframe=1"}]
[polldaddy:{"method":"iframe","type":"survey","src":"//clinicalpolls.polldaddy.com/s/health-care-reform-survey-what-would-make-a-difference-for-you?iframe=1"}]
On 15 years: Celebrating a nocturnist’s career longevity
“Nocturnist years are like dog years. So really we’re celebrating you for 105 years of service!”
Shawn Lee, MD, a day shift hospitalist at Overlake Medical Center in Bellevue, Wash. (where I work), said this about our colleague, Arash Nadershahi, MD, on the occasion of his 15th anniversary as a nocturnist with our group. Every hospitalist group should be so lucky to have someone like Arash among them, whether working nights or days.
When Arash joined our group the job simply entailed turning on the pager at 9 p.m. and coming in to the hospital only when the need arose. Some nights meant only answering some “cross-cover” calls from home, while other nights started with one or more patients needing admission right at the start of the shift.
As the months went by, patient volume climbed rapidly and Arash, as well as the nocturnists who joined us subsequently, began arriving at the hospital no later than the 9:00 p.m. shift start and staying in-house until 7 a.m. We never had a meeting or contentious conversation to make it official that the night shift changed to in-house all night instead of call-from-home. It just evolved that way to meet the need.
We all value Arash’s steady demeanor, excellent clinical skills, and good relationships with ED staff and nurses as well as patients. And for many years he and our other two nocturnists have covered all night shifts, including filling in when one of them is unexpectedly out for the birth of a child, illness, or other reason. The day doctors have never been called upon to work night shifts to cover an unexpected nocturnist absence.
Configuring the nocturnist position
A full-time nocturnist in our group works ten 10-hour night shifts and two 6-hour evening shifts (5-11 p.m.) per month. I like to think this has contributed to longevity for our nocturnists. One left last year after working nights for 10 years, and another just started his 9th year in the group.
The three nocturnists can work any schedule they like as long as one of them is on duty each night. For more than 10 years they’ve worked 7 consecutive night shifts followed by 14 off (that is sometimes interrupted by an evening shift). To my way of thinking, though, they’re essentially devoting 9 days to the practice for every seven consecutive shifts. The days before they start their rotation and after they complete it are spent preparing/recovering by adjusting their sleep, so aren’t really days of R&R.
For this work their compensation is very similar to that of full-time day shift doctors. The idea is that their compensation premium for working nights comes in the form of less work rather than more money; they work fewer and shorter shifts than their daytime counterparts. And we discourage moonlighting during all those days off. We want to provide the conditions for a healthy lifestyle to offset night work.
The longest-tenured nocturnist?
At 15 years of full-time work as a nocturnist, Arash may be one of the longest-tenured doctors in this role nationally. (I would love to hear about others who’ve been at it longer.) I like to think that our “pay ’em the same and work ’em less” approach may be a meaningful contributor to his longevity in the role, but I’m convinced his personal attributes are also a big factor.
His interests and creativity find their way into our workplace. For a while the day shift doctors would arrive to find our office full of motorcycle parts in various stages of assembly. Many of his doodles and drawings and witty writings are taped to the walls and cabinets. A few years ago he started writing haikus and before long everyone in the group joined in. This even led to one of our docs hosting a really fun party at which every guest wrote haikus and all had to guess the author of each one.
Other groups can’t count on finding someone as valuable as Arash, but they’ll have the best chance of it if they think carefully about how the nocturnist role is configured.
Dr. Nelson has had a career in clinical practice as a hospitalist starting in 1988. He is cofounder and past president of SHM, and principal in Nelson Flores Hospital Medicine Consultants. He is codirector for SHM’s practice management courses.
“Nocturnist years are like dog years. So really we’re celebrating you for 105 years of service!”
Shawn Lee, MD, a day shift hospitalist at Overlake Medical Center in Bellevue, Wash. (where I work), said this about our colleague, Arash Nadershahi, MD, on the occasion of his 15th anniversary as a nocturnist with our group. Every hospitalist group should be so lucky to have someone like Arash among them, whether working nights or days.
When Arash joined our group the job simply entailed turning on the pager at 9 p.m. and coming in to the hospital only when the need arose. Some nights meant only answering some “cross-cover” calls from home, while other nights started with one or more patients needing admission right at the start of the shift.
As the months went by, patient volume climbed rapidly and Arash, as well as the nocturnists who joined us subsequently, began arriving at the hospital no later than the 9:00 p.m. shift start and staying in-house until 7 a.m. We never had a meeting or contentious conversation to make it official that the night shift changed to in-house all night instead of call-from-home. It just evolved that way to meet the need.
We all value Arash’s steady demeanor, excellent clinical skills, and good relationships with ED staff and nurses as well as patients. And for many years he and our other two nocturnists have covered all night shifts, including filling in when one of them is unexpectedly out for the birth of a child, illness, or other reason. The day doctors have never been called upon to work night shifts to cover an unexpected nocturnist absence.
Configuring the nocturnist position
A full-time nocturnist in our group works ten 10-hour night shifts and two 6-hour evening shifts (5-11 p.m.) per month. I like to think this has contributed to longevity for our nocturnists. One left last year after working nights for 10 years, and another just started his 9th year in the group.
The three nocturnists can work any schedule they like as long as one of them is on duty each night. For more than 10 years they’ve worked 7 consecutive night shifts followed by 14 off (that is sometimes interrupted by an evening shift). To my way of thinking, though, they’re essentially devoting 9 days to the practice for every seven consecutive shifts. The days before they start their rotation and after they complete it are spent preparing/recovering by adjusting their sleep, so aren’t really days of R&R.
For this work their compensation is very similar to that of full-time day shift doctors. The idea is that their compensation premium for working nights comes in the form of less work rather than more money; they work fewer and shorter shifts than their daytime counterparts. And we discourage moonlighting during all those days off. We want to provide the conditions for a healthy lifestyle to offset night work.
The longest-tenured nocturnist?
At 15 years of full-time work as a nocturnist, Arash may be one of the longest-tenured doctors in this role nationally. (I would love to hear about others who’ve been at it longer.) I like to think that our “pay ’em the same and work ’em less” approach may be a meaningful contributor to his longevity in the role, but I’m convinced his personal attributes are also a big factor.
His interests and creativity find their way into our workplace. For a while the day shift doctors would arrive to find our office full of motorcycle parts in various stages of assembly. Many of his doodles and drawings and witty writings are taped to the walls and cabinets. A few years ago he started writing haikus and before long everyone in the group joined in. This even led to one of our docs hosting a really fun party at which every guest wrote haikus and all had to guess the author of each one.
Other groups can’t count on finding someone as valuable as Arash, but they’ll have the best chance of it if they think carefully about how the nocturnist role is configured.
Dr. Nelson has had a career in clinical practice as a hospitalist starting in 1988. He is cofounder and past president of SHM, and principal in Nelson Flores Hospital Medicine Consultants. He is codirector for SHM’s practice management courses.
“Nocturnist years are like dog years. So really we’re celebrating you for 105 years of service!”
Shawn Lee, MD, a day shift hospitalist at Overlake Medical Center in Bellevue, Wash. (where I work), said this about our colleague, Arash Nadershahi, MD, on the occasion of his 15th anniversary as a nocturnist with our group. Every hospitalist group should be so lucky to have someone like Arash among them, whether working nights or days.
When Arash joined our group the job simply entailed turning on the pager at 9 p.m. and coming in to the hospital only when the need arose. Some nights meant only answering some “cross-cover” calls from home, while other nights started with one or more patients needing admission right at the start of the shift.
As the months went by, patient volume climbed rapidly and Arash, as well as the nocturnists who joined us subsequently, began arriving at the hospital no later than the 9:00 p.m. shift start and staying in-house until 7 a.m. We never had a meeting or contentious conversation to make it official that the night shift changed to in-house all night instead of call-from-home. It just evolved that way to meet the need.
We all value Arash’s steady demeanor, excellent clinical skills, and good relationships with ED staff and nurses as well as patients. And for many years he and our other two nocturnists have covered all night shifts, including filling in when one of them is unexpectedly out for the birth of a child, illness, or other reason. The day doctors have never been called upon to work night shifts to cover an unexpected nocturnist absence.
Configuring the nocturnist position
A full-time nocturnist in our group works ten 10-hour night shifts and two 6-hour evening shifts (5-11 p.m.) per month. I like to think this has contributed to longevity for our nocturnists. One left last year after working nights for 10 years, and another just started his 9th year in the group.
The three nocturnists can work any schedule they like as long as one of them is on duty each night. For more than 10 years they’ve worked 7 consecutive night shifts followed by 14 off (that is sometimes interrupted by an evening shift). To my way of thinking, though, they’re essentially devoting 9 days to the practice for every seven consecutive shifts. The days before they start their rotation and after they complete it are spent preparing/recovering by adjusting their sleep, so aren’t really days of R&R.
For this work their compensation is very similar to that of full-time day shift doctors. The idea is that their compensation premium for working nights comes in the form of less work rather than more money; they work fewer and shorter shifts than their daytime counterparts. And we discourage moonlighting during all those days off. We want to provide the conditions for a healthy lifestyle to offset night work.
The longest-tenured nocturnist?
At 15 years of full-time work as a nocturnist, Arash may be one of the longest-tenured doctors in this role nationally. (I would love to hear about others who’ve been at it longer.) I like to think that our “pay ’em the same and work ’em less” approach may be a meaningful contributor to his longevity in the role, but I’m convinced his personal attributes are also a big factor.
His interests and creativity find their way into our workplace. For a while the day shift doctors would arrive to find our office full of motorcycle parts in various stages of assembly. Many of his doodles and drawings and witty writings are taped to the walls and cabinets. A few years ago he started writing haikus and before long everyone in the group joined in. This even led to one of our docs hosting a really fun party at which every guest wrote haikus and all had to guess the author of each one.
Other groups can’t count on finding someone as valuable as Arash, but they’ll have the best chance of it if they think carefully about how the nocturnist role is configured.
Dr. Nelson has had a career in clinical practice as a hospitalist starting in 1988. He is cofounder and past president of SHM, and principal in Nelson Flores Hospital Medicine Consultants. He is codirector for SHM’s practice management courses.
Survey highlights care gaps for transgender men
SAN DIEGO – Most transgender men have visited a gynecologist’s office at least once, but just 37% attend annual visits, results from a small survey showed.
“We’re seeing a large need and lack of access to gynecologic care,” Adriana J. Wong, the study author, said in an interview at the annual meeting of the American College of Obstetricians and Gynecologists. “Some barriers that we’ve identified are fear of mistreatment, a perceived lack of informed providers, and gender dysphoria.”
In an effort to assess transgender men’s experiences with, ability to access, and understanding of gynecologic care, Ms. Wong and her associates distributed an anonymous Web-based and paper-based survey to a convenience sample of transgender men in the Miami area. The mean age of the 41 respondents was 28 years, 56% were white, 41% had a high school diploma, 27% had a college degree, and 17% had a graduate degree.
The majority of survey participants (78%) reported having been to a gynecologist, 37% attended annual visits, 78% had health insurance, 56% delayed care because of gender identity concerns, and 20% experienced mistreatment at a gynecologist’s office.
Respondents reported delaying or avoiding care because they “felt uncomfortable with the extremely gendered experience of [gynecologic] care,” “fear of mistreatment,” and “my dysphoria prevented me. Plus, I wasn’t sure if there were friendly ob.gyns. around.”
“One of the most distinctive things to me is that we had a pretty well-insured population in our sample, and they were mostly Caucasian,” said Ms. Wong, a second-year medical student at the University of Miami. “Even though almost 80% were insured, [fewer] than 40% were receiving annual visits. This is the population that would potentially have the best possibility of receiving care, but they’re not seeking it out.”
The researchers reported having no relevant financial disclosures.
SAN DIEGO – Most transgender men have visited a gynecologist’s office at least once, but just 37% attend annual visits, results from a small survey showed.
“We’re seeing a large need and lack of access to gynecologic care,” Adriana J. Wong, the study author, said in an interview at the annual meeting of the American College of Obstetricians and Gynecologists. “Some barriers that we’ve identified are fear of mistreatment, a perceived lack of informed providers, and gender dysphoria.”
In an effort to assess transgender men’s experiences with, ability to access, and understanding of gynecologic care, Ms. Wong and her associates distributed an anonymous Web-based and paper-based survey to a convenience sample of transgender men in the Miami area. The mean age of the 41 respondents was 28 years, 56% were white, 41% had a high school diploma, 27% had a college degree, and 17% had a graduate degree.
The majority of survey participants (78%) reported having been to a gynecologist, 37% attended annual visits, 78% had health insurance, 56% delayed care because of gender identity concerns, and 20% experienced mistreatment at a gynecologist’s office.
Respondents reported delaying or avoiding care because they “felt uncomfortable with the extremely gendered experience of [gynecologic] care,” “fear of mistreatment,” and “my dysphoria prevented me. Plus, I wasn’t sure if there were friendly ob.gyns. around.”
“One of the most distinctive things to me is that we had a pretty well-insured population in our sample, and they were mostly Caucasian,” said Ms. Wong, a second-year medical student at the University of Miami. “Even though almost 80% were insured, [fewer] than 40% were receiving annual visits. This is the population that would potentially have the best possibility of receiving care, but they’re not seeking it out.”
The researchers reported having no relevant financial disclosures.
SAN DIEGO – Most transgender men have visited a gynecologist’s office at least once, but just 37% attend annual visits, results from a small survey showed.
“We’re seeing a large need and lack of access to gynecologic care,” Adriana J. Wong, the study author, said in an interview at the annual meeting of the American College of Obstetricians and Gynecologists. “Some barriers that we’ve identified are fear of mistreatment, a perceived lack of informed providers, and gender dysphoria.”
In an effort to assess transgender men’s experiences with, ability to access, and understanding of gynecologic care, Ms. Wong and her associates distributed an anonymous Web-based and paper-based survey to a convenience sample of transgender men in the Miami area. The mean age of the 41 respondents was 28 years, 56% were white, 41% had a high school diploma, 27% had a college degree, and 17% had a graduate degree.
The majority of survey participants (78%) reported having been to a gynecologist, 37% attended annual visits, 78% had health insurance, 56% delayed care because of gender identity concerns, and 20% experienced mistreatment at a gynecologist’s office.
Respondents reported delaying or avoiding care because they “felt uncomfortable with the extremely gendered experience of [gynecologic] care,” “fear of mistreatment,” and “my dysphoria prevented me. Plus, I wasn’t sure if there were friendly ob.gyns. around.”
“One of the most distinctive things to me is that we had a pretty well-insured population in our sample, and they were mostly Caucasian,” said Ms. Wong, a second-year medical student at the University of Miami. “Even though almost 80% were insured, [fewer] than 40% were receiving annual visits. This is the population that would potentially have the best possibility of receiving care, but they’re not seeking it out.”
The researchers reported having no relevant financial disclosures.
AT ACOG 2017
Key clinical point:
Major finding: Most transgender men (78%) have been to a gynecologist at least once, but just 37% attend annual visits.
Data source: Responses from a survey of 41 transgender men in the Miami area.
Disclosures: The researchers reported having no relevant financial disclosures.
It Pays to Get Screened for Colon Cancer
Although cancer death rates have been decreasing for the general population, they’ve been increasing for American Indians, according to the American Indian Cancer Foundation (AICAF). The AICAF cites a number of barriers to prevention and care, such as low awareness of risks, distrust of medical systems and research, health beliefs that may conflict with prevention practices, and low awareness of screening options.
The Northern Plains region has some of the highest rates of cancer diagnoses and death in the U.S. Colon cancer, for example, is 53% higher in Northern Plains American Indians, AICAF says. Although screening rates are improving, fewer than half of Northern Plains American Indians aged ≥ 50 years have had a colorectal cancer screening, according to the Association of American Indian Physicians.
The cancer mortality rates are the result of a “complex set of factors” that the AICAF is beginning to address with a comprehensive set of approaches. For instance, in addition to educating the public, AICAF, in partnership with the Minnesota Department of Health and Get Your Rear in Gear Colon Cancer Coalition is putting money where its mouth is, with the “Refer-a-Relative” program.
“We are all related,” the campaign says: “Help your community and end colon cancer!” Refer-a-Relative encourages Native Americans in the Minneapolis-St. Paul metropolitan area to get screened, and then to refer up to 5 relatives aged ≥ 50 years for screening. Patients receive a $20 gift card for completing screening, and $10 for each relative who completes screening. The relatives receive a $20 gift card and can refer more people.
The screening project is 1 branch of the AICAF’s interest in innovating clinical systems at IHS, Tribal, and Urban (ITU) clinics. Much of the work is based on the Improving Northern Plains American Indian Colorectal Cancer Screening (INPACS) project with ITU clinics. The AICAF invites interested ITU clinics to join the Clinical Cancer Screening Network. For more information, infographics, and other patient education materials, visit www.americanindiancancer.org.
Although cancer death rates have been decreasing for the general population, they’ve been increasing for American Indians, according to the American Indian Cancer Foundation (AICAF). The AICAF cites a number of barriers to prevention and care, such as low awareness of risks, distrust of medical systems and research, health beliefs that may conflict with prevention practices, and low awareness of screening options.
The Northern Plains region has some of the highest rates of cancer diagnoses and death in the U.S. Colon cancer, for example, is 53% higher in Northern Plains American Indians, AICAF says. Although screening rates are improving, fewer than half of Northern Plains American Indians aged ≥ 50 years have had a colorectal cancer screening, according to the Association of American Indian Physicians.
The cancer mortality rates are the result of a “complex set of factors” that the AICAF is beginning to address with a comprehensive set of approaches. For instance, in addition to educating the public, AICAF, in partnership with the Minnesota Department of Health and Get Your Rear in Gear Colon Cancer Coalition is putting money where its mouth is, with the “Refer-a-Relative” program.
“We are all related,” the campaign says: “Help your community and end colon cancer!” Refer-a-Relative encourages Native Americans in the Minneapolis-St. Paul metropolitan area to get screened, and then to refer up to 5 relatives aged ≥ 50 years for screening. Patients receive a $20 gift card for completing screening, and $10 for each relative who completes screening. The relatives receive a $20 gift card and can refer more people.
The screening project is 1 branch of the AICAF’s interest in innovating clinical systems at IHS, Tribal, and Urban (ITU) clinics. Much of the work is based on the Improving Northern Plains American Indian Colorectal Cancer Screening (INPACS) project with ITU clinics. The AICAF invites interested ITU clinics to join the Clinical Cancer Screening Network. For more information, infographics, and other patient education materials, visit www.americanindiancancer.org.
Although cancer death rates have been decreasing for the general population, they’ve been increasing for American Indians, according to the American Indian Cancer Foundation (AICAF). The AICAF cites a number of barriers to prevention and care, such as low awareness of risks, distrust of medical systems and research, health beliefs that may conflict with prevention practices, and low awareness of screening options.
The Northern Plains region has some of the highest rates of cancer diagnoses and death in the U.S. Colon cancer, for example, is 53% higher in Northern Plains American Indians, AICAF says. Although screening rates are improving, fewer than half of Northern Plains American Indians aged ≥ 50 years have had a colorectal cancer screening, according to the Association of American Indian Physicians.
The cancer mortality rates are the result of a “complex set of factors” that the AICAF is beginning to address with a comprehensive set of approaches. For instance, in addition to educating the public, AICAF, in partnership with the Minnesota Department of Health and Get Your Rear in Gear Colon Cancer Coalition is putting money where its mouth is, with the “Refer-a-Relative” program.
“We are all related,” the campaign says: “Help your community and end colon cancer!” Refer-a-Relative encourages Native Americans in the Minneapolis-St. Paul metropolitan area to get screened, and then to refer up to 5 relatives aged ≥ 50 years for screening. Patients receive a $20 gift card for completing screening, and $10 for each relative who completes screening. The relatives receive a $20 gift card and can refer more people.
The screening project is 1 branch of the AICAF’s interest in innovating clinical systems at IHS, Tribal, and Urban (ITU) clinics. Much of the work is based on the Improving Northern Plains American Indian Colorectal Cancer Screening (INPACS) project with ITU clinics. The AICAF invites interested ITU clinics to join the Clinical Cancer Screening Network. For more information, infographics, and other patient education materials, visit www.americanindiancancer.org.
HL survivors should be screened for CAD after chest irradiation
VIENNA, AUSTRIA—Hodgkin lymphoma (HL) survivors who received chest irradiation should be screened for coronary artery disease (CAD), according to researchers.
The team evaluated HL survivors who underwent mediastinal irradiation 20 years prior to study initiation.
These individuals were more likely to have CAD and to have more severe CAD than matched control subjects.
The researchers presented these findings at ICNC 2017, the International Conference on Nuclear Cardiology and Cardiac CT (abstract P118).
“Patients with Hodgkin lymphoma receive high-dose mediastinal irradiation at a young age as part of their treatment,” said Alexander van Rosendael, MD, of Leiden University Medical Centre in the Netherlands.
“There is an ongoing debate about whether to screen patients who get chest irradiation for coronary artery disease.”
Therefore, Dr van Rosendael and his colleagues assessed the extent, severity, and location of CAD in HL survivors who had received chest irradiation.
The study included 79 patients who had been free of HL for at least 10 years and had received mediastinal irradiation 20 years ago, plus 273 control subjects without HL or irradiation.
CAD was assessed using coronary computed tomography angiography (CTA). To assess differences in CAD between patients and controls, they were matched in a 1:3 fashion by age, gender, diabetes, hypertension, hypercholesterolemia, family history of CAD, and smoking status.
Patients were 45 years old, on average, and the presence of cardiovascular risk factors was low overall.
Forty-two percent of patients had no atherosclerosis on coronary CTA, compared to 64% of controls (P<0.001).
Regarding the extent and severity of CAD, HL patients had significantly more multi-vessel CAD than controls. Ten percent of patients had 2-vessel disease, and 24% had 3-vessel disease, compared to 6% and 9% of controls, respectively (P=0.001).
The segment involvement score (which measures overall coronary plaque distribution) and the segment stenosis score (which measures overall coronary plaque extent and severity) were significantly higher for patients than for controls (P<0.001 and P=0.034, respectively).
Regarding the location of CAD, patients had significantly more coronary plaques in the left main (17% vs 6%, P=0.004), proximal left anterior descending (30% vs 16%, P=0.004), proximal right coronary artery (25% vs 10%, P<0.001), and proximal left circumflex (14% vs 6%, P=0.022), but not in non-proximal coronary segments.
Patients had about a 4-fold higher risk of proximal plaque and about 3-fold higher risk of proximal obstructive stenosis compared to controls (odds ratios, 4.1 and 2.9, respectively; P values, <0.001 and 0.025, respectively).
“Hodgkin patients who have chest irradiation have much more CAD than people of the same age who did not have irradiation,” Dr van Rosendael said.
“The CAD occurred at a young age—patients were 45 years old, on average—and was probably caused by the irradiation. The CTA was done about 20 years after chest irradiation, so there was time for CAD to develop.”
“What was remarkable was that irradiated patients had all the features of high-risk CAD, including high stenosis severity, proximal location, and extensive disease. We know that the proximal location of the disease is much riskier, and this may explain why Hodgkin patients have such poor cardiovascular outcomes when they get older.”
Dr van Rosendael explained that irradiation of the chest can cause inflammation of the coronary arteries, making patients more vulnerable to developing CAD. But it is not known why the CAD in irradiated patients tends to be proximally located.
He said the finding of more, and more severe, CAD in irradiated patients supports the argument for screening.
“When you see CAD in patients who received chest irradiation, it is high-risk CAD,” he said. “Such patients should be screened at regular intervals after irradiation so that CAD can be spotted early and early treatment can be initiated.”
“These patients are around 45 years old, and they are almost all asymptomatic. If you see a severe left main stenosis by screening with CTA (which occurred in 4%), then you can start statin therapy and perform revascularization, which may improve outcome. We know such treatment reduces the risk of events in non-irradiated patients, so it seems likely that it would benefit Hodgkin patients.” 
VIENNA, AUSTRIA—Hodgkin lymphoma (HL) survivors who received chest irradiation should be screened for coronary artery disease (CAD), according to researchers.
The team evaluated HL survivors who underwent mediastinal irradiation 20 years prior to study initiation.
These individuals were more likely to have CAD and to have more severe CAD than matched control subjects.
The researchers presented these findings at ICNC 2017, the International Conference on Nuclear Cardiology and Cardiac CT (abstract P118).
“Patients with Hodgkin lymphoma receive high-dose mediastinal irradiation at a young age as part of their treatment,” said Alexander van Rosendael, MD, of Leiden University Medical Centre in the Netherlands.
“There is an ongoing debate about whether to screen patients who get chest irradiation for coronary artery disease.”
Therefore, Dr van Rosendael and his colleagues assessed the extent, severity, and location of CAD in HL survivors who had received chest irradiation.
The study included 79 patients who had been free of HL for at least 10 years and had received mediastinal irradiation 20 years ago, plus 273 control subjects without HL or irradiation.
CAD was assessed using coronary computed tomography angiography (CTA). To assess differences in CAD between patients and controls, they were matched in a 1:3 fashion by age, gender, diabetes, hypertension, hypercholesterolemia, family history of CAD, and smoking status.
Patients were 45 years old, on average, and the presence of cardiovascular risk factors was low overall.
Forty-two percent of patients had no atherosclerosis on coronary CTA, compared to 64% of controls (P<0.001).
Regarding the extent and severity of CAD, HL patients had significantly more multi-vessel CAD than controls. Ten percent of patients had 2-vessel disease, and 24% had 3-vessel disease, compared to 6% and 9% of controls, respectively (P=0.001).
The segment involvement score (which measures overall coronary plaque distribution) and the segment stenosis score (which measures overall coronary plaque extent and severity) were significantly higher for patients than for controls (P<0.001 and P=0.034, respectively).
Regarding the location of CAD, patients had significantly more coronary plaques in the left main (17% vs 6%, P=0.004), proximal left anterior descending (30% vs 16%, P=0.004), proximal right coronary artery (25% vs 10%, P<0.001), and proximal left circumflex (14% vs 6%, P=0.022), but not in non-proximal coronary segments.
Patients had about a 4-fold higher risk of proximal plaque and about 3-fold higher risk of proximal obstructive stenosis compared to controls (odds ratios, 4.1 and 2.9, respectively; P values, <0.001 and 0.025, respectively).
“Hodgkin patients who have chest irradiation have much more CAD than people of the same age who did not have irradiation,” Dr van Rosendael said.
“The CAD occurred at a young age—patients were 45 years old, on average—and was probably caused by the irradiation. The CTA was done about 20 years after chest irradiation, so there was time for CAD to develop.”
“What was remarkable was that irradiated patients had all the features of high-risk CAD, including high stenosis severity, proximal location, and extensive disease. We know that the proximal location of the disease is much riskier, and this may explain why Hodgkin patients have such poor cardiovascular outcomes when they get older.”
Dr van Rosendael explained that irradiation of the chest can cause inflammation of the coronary arteries, making patients more vulnerable to developing CAD. But it is not known why the CAD in irradiated patients tends to be proximally located.
He said the finding of more, and more severe, CAD in irradiated patients supports the argument for screening.
“When you see CAD in patients who received chest irradiation, it is high-risk CAD,” he said. “Such patients should be screened at regular intervals after irradiation so that CAD can be spotted early and early treatment can be initiated.”
“These patients are around 45 years old, and they are almost all asymptomatic. If you see a severe left main stenosis by screening with CTA (which occurred in 4%), then you can start statin therapy and perform revascularization, which may improve outcome. We know such treatment reduces the risk of events in non-irradiated patients, so it seems likely that it would benefit Hodgkin patients.”
VIENNA, AUSTRIA—Hodgkin lymphoma (HL) survivors who received chest irradiation should be screened for coronary artery disease (CAD), according to researchers.
The team evaluated HL survivors who underwent mediastinal irradiation 20 years prior to study initiation.
These individuals were more likely to have CAD and to have more severe CAD than matched control subjects.
The researchers presented these findings at ICNC 2017, the International Conference on Nuclear Cardiology and Cardiac CT (abstract P118).
“Patients with Hodgkin lymphoma receive high-dose mediastinal irradiation at a young age as part of their treatment,” said Alexander van Rosendael, MD, of Leiden University Medical Centre in the Netherlands.
“There is an ongoing debate about whether to screen patients who get chest irradiation for coronary artery disease.”
Therefore, Dr van Rosendael and his colleagues assessed the extent, severity, and location of CAD in HL survivors who had received chest irradiation.
The study included 79 patients who had been free of HL for at least 10 years and had received mediastinal irradiation 20 years ago, plus 273 control subjects without HL or irradiation.
CAD was assessed using coronary computed tomography angiography (CTA). To assess differences in CAD between patients and controls, they were matched in a 1:3 fashion by age, gender, diabetes, hypertension, hypercholesterolemia, family history of CAD, and smoking status.
Patients were 45 years old, on average, and the presence of cardiovascular risk factors was low overall.
Forty-two percent of patients had no atherosclerosis on coronary CTA, compared to 64% of controls (P<0.001).
Regarding the extent and severity of CAD, HL patients had significantly more multi-vessel CAD than controls. Ten percent of patients had 2-vessel disease, and 24% had 3-vessel disease, compared to 6% and 9% of controls, respectively (P=0.001).
The segment involvement score (which measures overall coronary plaque distribution) and the segment stenosis score (which measures overall coronary plaque extent and severity) were significantly higher for patients than for controls (P<0.001 and P=0.034, respectively).
Regarding the location of CAD, patients had significantly more coronary plaques in the left main (17% vs 6%, P=0.004), proximal left anterior descending (30% vs 16%, P=0.004), proximal right coronary artery (25% vs 10%, P<0.001), and proximal left circumflex (14% vs 6%, P=0.022), but not in non-proximal coronary segments.
Patients had about a 4-fold higher risk of proximal plaque and about 3-fold higher risk of proximal obstructive stenosis compared to controls (odds ratios, 4.1 and 2.9, respectively; P values, <0.001 and 0.025, respectively).
“Hodgkin patients who have chest irradiation have much more CAD than people of the same age who did not have irradiation,” Dr van Rosendael said.
“The CAD occurred at a young age—patients were 45 years old, on average—and was probably caused by the irradiation. The CTA was done about 20 years after chest irradiation, so there was time for CAD to develop.”
“What was remarkable was that irradiated patients had all the features of high-risk CAD, including high stenosis severity, proximal location, and extensive disease. We know that the proximal location of the disease is much riskier, and this may explain why Hodgkin patients have such poor cardiovascular outcomes when they get older.”
Dr van Rosendael explained that irradiation of the chest can cause inflammation of the coronary arteries, making patients more vulnerable to developing CAD. But it is not known why the CAD in irradiated patients tends to be proximally located.
He said the finding of more, and more severe, CAD in irradiated patients supports the argument for screening.
“When you see CAD in patients who received chest irradiation, it is high-risk CAD,” he said. “Such patients should be screened at regular intervals after irradiation so that CAD can be spotted early and early treatment can be initiated.”
“These patients are around 45 years old, and they are almost all asymptomatic. If you see a severe left main stenosis by screening with CTA (which occurred in 4%), then you can start statin therapy and perform revascularization, which may improve outcome. We know such treatment reduces the risk of events in non-irradiated patients, so it seems likely that it would benefit Hodgkin patients.”
Compound inhibits translation program to treat MM
A new compound has shown promise for treating multiple myeloma (MM) by inhibiting the oncogenic MYC-driven translation program supporting the disease, according to researchers.
The compound is CMLD01059, a derivative of natural products called rocaglates that are known to interfere with translation.
CMLD010509 induced apoptosis in MM cells in culture and exhibited anti-myeloma activity in 3 different mouse models.
In addition, the compound was well-tolerated by the mice and spared normal cells in culture.
Salomon Manier, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, and his colleagues reported these results in Science Translational Medicine.
The researchers found that CMLD01059 treatment significantly reduced the levels of 54 proteins in MM cell lines, including 5 known drivers of tumor progression—MYC, MDM2, CCND1, MAF, and MCL-1.
Further investigation confirmed that CMLD010509 inhibits the translation of oncoproteins that support the proliferation and survival of MM cells.
The researchers also found that CMLD010509 triggered a “strong” and “rapid” apoptotic response in MM cells (NCI-H929 and MM1S).
So the team tested the anti-myeloma activity of CMLD010509 in mouse models.
In one model (mice injected with MM1S cells), CMLD010509 “caused a marked reduction in tumor burden,” according to the researchers.
The median survival was 47 days in CMLD010509-treated mice, compared to 35 days in control mice (P<0.001).
The researchers also noted that 4 weeks of CMLD010509 treatment was well-tolerated in the mice, who maintained their weight and normal complete blood counts.
In another MM model (mice injected with KMS-11 cells), the mice received CMLD010509 or vehicle control twice a week for 4 weeks and were sacrificed at the end of treatment.
Immunohistochemistry studies conducted on bone marrow samples revealed a decrease in CD138+ plasma cells, depletion of MYC, and inhibition of proliferation in the CMLD010509-treated mice.
For the last model, the researchers injected transplantable mouse MM cells into C57BL/6 mice. The team noted that these cells are driven by plasma cell-specific MYC overexpression (Vk*Myc cells).
The mice received CMLD010509 or vehicle control twice a week starting 1 week after cell inoculation.
The researchers said CMLD010509 was well-tolerated, and they observed a “robust” decrease of M-spike in the treated mice that was associated with a significant improvement in survival.
The median survival was 39 days in the control mice, but it had not been reached by 90 days in the treated mice (P=0.0019).
The researchers said these results support targeting translation with rocaglates to treat MM.
A new compound has shown promise for treating multiple myeloma (MM) by inhibiting the oncogenic MYC-driven translation program supporting the disease, according to researchers.
The compound is CMLD01059, a derivative of natural products called rocaglates that are known to interfere with translation.
CMLD010509 induced apoptosis in MM cells in culture and exhibited anti-myeloma activity in 3 different mouse models.
In addition, the compound was well-tolerated by the mice and spared normal cells in culture.
Salomon Manier, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, and his colleagues reported these results in Science Translational Medicine.
The researchers found that CMLD01059 treatment significantly reduced the levels of 54 proteins in MM cell lines, including 5 known drivers of tumor progression—MYC, MDM2, CCND1, MAF, and MCL-1.
Further investigation confirmed that CMLD010509 inhibits the translation of oncoproteins that support the proliferation and survival of MM cells.
The researchers also found that CMLD010509 triggered a “strong” and “rapid” apoptotic response in MM cells (NCI-H929 and MM1S).
So the team tested the anti-myeloma activity of CMLD010509 in mouse models.
In one model (mice injected with MM1S cells), CMLD010509 “caused a marked reduction in tumor burden,” according to the researchers.
The median survival was 47 days in CMLD010509-treated mice, compared to 35 days in control mice (P<0.001).
The researchers also noted that 4 weeks of CMLD010509 treatment was well-tolerated in the mice, who maintained their weight and normal complete blood counts.
In another MM model (mice injected with KMS-11 cells), the mice received CMLD010509 or vehicle control twice a week for 4 weeks and were sacrificed at the end of treatment.
Immunohistochemistry studies conducted on bone marrow samples revealed a decrease in CD138+ plasma cells, depletion of MYC, and inhibition of proliferation in the CMLD010509-treated mice.
For the last model, the researchers injected transplantable mouse MM cells into C57BL/6 mice. The team noted that these cells are driven by plasma cell-specific MYC overexpression (Vk*Myc cells).
The mice received CMLD010509 or vehicle control twice a week starting 1 week after cell inoculation.
The researchers said CMLD010509 was well-tolerated, and they observed a “robust” decrease of M-spike in the treated mice that was associated with a significant improvement in survival.
The median survival was 39 days in the control mice, but it had not been reached by 90 days in the treated mice (P=0.0019).
The researchers said these results support targeting translation with rocaglates to treat MM.
A new compound has shown promise for treating multiple myeloma (MM) by inhibiting the oncogenic MYC-driven translation program supporting the disease, according to researchers.
The compound is CMLD01059, a derivative of natural products called rocaglates that are known to interfere with translation.
CMLD010509 induced apoptosis in MM cells in culture and exhibited anti-myeloma activity in 3 different mouse models.
In addition, the compound was well-tolerated by the mice and spared normal cells in culture.
Salomon Manier, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, and his colleagues reported these results in Science Translational Medicine.
The researchers found that CMLD01059 treatment significantly reduced the levels of 54 proteins in MM cell lines, including 5 known drivers of tumor progression—MYC, MDM2, CCND1, MAF, and MCL-1.
Further investigation confirmed that CMLD010509 inhibits the translation of oncoproteins that support the proliferation and survival of MM cells.
The researchers also found that CMLD010509 triggered a “strong” and “rapid” apoptotic response in MM cells (NCI-H929 and MM1S).
So the team tested the anti-myeloma activity of CMLD010509 in mouse models.
In one model (mice injected with MM1S cells), CMLD010509 “caused a marked reduction in tumor burden,” according to the researchers.
The median survival was 47 days in CMLD010509-treated mice, compared to 35 days in control mice (P<0.001).
The researchers also noted that 4 weeks of CMLD010509 treatment was well-tolerated in the mice, who maintained their weight and normal complete blood counts.
In another MM model (mice injected with KMS-11 cells), the mice received CMLD010509 or vehicle control twice a week for 4 weeks and were sacrificed at the end of treatment.
Immunohistochemistry studies conducted on bone marrow samples revealed a decrease in CD138+ plasma cells, depletion of MYC, and inhibition of proliferation in the CMLD010509-treated mice.
For the last model, the researchers injected transplantable mouse MM cells into C57BL/6 mice. The team noted that these cells are driven by plasma cell-specific MYC overexpression (Vk*Myc cells).
The mice received CMLD010509 or vehicle control twice a week starting 1 week after cell inoculation.
The researchers said CMLD010509 was well-tolerated, and they observed a “robust” decrease of M-spike in the treated mice that was associated with a significant improvement in survival.
The median survival was 39 days in the control mice, but it had not been reached by 90 days in the treated mice (P=0.0019).
The researchers said these results support targeting translation with rocaglates to treat MM.
EMA recommends drug receive orphan designation for PNH
The European Medicines Agency (EMA) has recommended orphan drug designation for the complement C3 inhibitor APL-2 as a treatment for paroxysmal nocturnal hemoglobinuria (PNH).
APL-2 is a synthetic cyclic peptide conjugated to a polyethylene glycol polymer that binds specifically to C3 and C3b, blocking all 3 pathways of complement activation (classical, lectin, and alternative).
This comprehensive inhibition of complement-mediated pathology may have the potential to control symptoms and modify underlying disease in patients with PNH, according to Apellis Pharmaceuticals, Inc., the company developing APL-2.
APL-2 has been evaluated in a pair of phase 1 studies of healthy volunteers. Results from these studies were presented at the 2016 ASH Annual Meeting (abstract 1251).
Now, Apellis is evaluating APL-2 in PNH patients in a pair of phase 1b trials.
In PADDOCK (NCT02588833), researchers are assessing the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of multiple doses of APL-2 administered by daily subcutaneous injection in patients with PNH who have not received the standard of care in the past.
In PHAROAH (NCT02264639), researchers are assessing the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of APL-2 administered by subcutaneous injection as an add-on to the standard of care in patients with PNH.
About orphan designation
Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.
Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval. The designation also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.
The EMA adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The European Commission typically makes a decision within 30 days.
The European Medicines Agency (EMA) has recommended orphan drug designation for the complement C3 inhibitor APL-2 as a treatment for paroxysmal nocturnal hemoglobinuria (PNH).
APL-2 is a synthetic cyclic peptide conjugated to a polyethylene glycol polymer that binds specifically to C3 and C3b, blocking all 3 pathways of complement activation (classical, lectin, and alternative).
This comprehensive inhibition of complement-mediated pathology may have the potential to control symptoms and modify underlying disease in patients with PNH, according to Apellis Pharmaceuticals, Inc., the company developing APL-2.
APL-2 has been evaluated in a pair of phase 1 studies of healthy volunteers. Results from these studies were presented at the 2016 ASH Annual Meeting (abstract 1251).
Now, Apellis is evaluating APL-2 in PNH patients in a pair of phase 1b trials.
In PADDOCK (NCT02588833), researchers are assessing the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of multiple doses of APL-2 administered by daily subcutaneous injection in patients with PNH who have not received the standard of care in the past.
In PHAROAH (NCT02264639), researchers are assessing the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of APL-2 administered by subcutaneous injection as an add-on to the standard of care in patients with PNH.
About orphan designation
Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.
Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval. The designation also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.
The EMA adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The European Commission typically makes a decision within 30 days.
The European Medicines Agency (EMA) has recommended orphan drug designation for the complement C3 inhibitor APL-2 as a treatment for paroxysmal nocturnal hemoglobinuria (PNH).
APL-2 is a synthetic cyclic peptide conjugated to a polyethylene glycol polymer that binds specifically to C3 and C3b, blocking all 3 pathways of complement activation (classical, lectin, and alternative).
This comprehensive inhibition of complement-mediated pathology may have the potential to control symptoms and modify underlying disease in patients with PNH, according to Apellis Pharmaceuticals, Inc., the company developing APL-2.
APL-2 has been evaluated in a pair of phase 1 studies of healthy volunteers. Results from these studies were presented at the 2016 ASH Annual Meeting (abstract 1251).
Now, Apellis is evaluating APL-2 in PNH patients in a pair of phase 1b trials.
In PADDOCK (NCT02588833), researchers are assessing the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of multiple doses of APL-2 administered by daily subcutaneous injection in patients with PNH who have not received the standard of care in the past.
In PHAROAH (NCT02264639), researchers are assessing the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of APL-2 administered by subcutaneous injection as an add-on to the standard of care in patients with PNH.
About orphan designation
Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.
Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval. The designation also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.
The EMA adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The European Commission typically makes a decision within 30 days.
Dry spots on lower legs
The FP made the presumptive diagnosis of nummular eczema, but recognized that a fungal infection and psoriasis were part of the differential diagnosis. He performed a potassium hydroxide (KOH) preparation, which was negative for hyphae and fungal elements. (See a video on how to perform a KOH preparation here: http://www.mdedge.com/jfponline/article/100603/dermatology/koh-preparation.) In order to explore whether this might be a case of guttate psoriasis, the FP asked about any preceding strep pharyngitis or other respiratory infections. The patient, however, had not had any preceding infections. The FP also checked her nails, scalp, and umbilicus for other signs of psoriasis, but found none. The FP was now confident in making a clinical diagnosis of nummular eczema (also known as nummular dermatitis).
Nummular eczema is a type of eczema characterized by circular or oval-shaped scaling plaques with well-defined borders. (“Nummus” is Latin for “coin.”) Nummular eczema produces multiple lesions that are most commonly found on the dorsa of the hands, arms, and legs.
Patients who have a history of atopic dermatitis are more likely to get nummular eczema even after they outgrow the atopic dermatitis. The 2 conditions involve problems with the barrier function of the skin, and emollients are helpful for the prevention and treatment of both.
In this case, the FP prescribed 0.1% triamcinolone ointment to be applied twice daily until the lesions resolved. At a one-month follow-up appointment, the patient indicated that her legs were now smooth and she was happy that she could shave them again. The FP told her that it would be a good idea to use emollients after bathing to keep the skin moist in order to prevent future episodes of nummular eczema.
Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Wah Y, Usatine R. Eczema. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013.
To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/
You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com
The FP made the presumptive diagnosis of nummular eczema, but recognized that a fungal infection and psoriasis were part of the differential diagnosis. He performed a potassium hydroxide (KOH) preparation, which was negative for hyphae and fungal elements. (See a video on how to perform a KOH preparation here: http://www.mdedge.com/jfponline/article/100603/dermatology/koh-preparation.) In order to explore whether this might be a case of guttate psoriasis, the FP asked about any preceding strep pharyngitis or other respiratory infections. The patient, however, had not had any preceding infections. The FP also checked her nails, scalp, and umbilicus for other signs of psoriasis, but found none. The FP was now confident in making a clinical diagnosis of nummular eczema (also known as nummular dermatitis).
Nummular eczema is a type of eczema characterized by circular or oval-shaped scaling plaques with well-defined borders. (“Nummus” is Latin for “coin.”) Nummular eczema produces multiple lesions that are most commonly found on the dorsa of the hands, arms, and legs.
Patients who have a history of atopic dermatitis are more likely to get nummular eczema even after they outgrow the atopic dermatitis. The 2 conditions involve problems with the barrier function of the skin, and emollients are helpful for the prevention and treatment of both.
In this case, the FP prescribed 0.1% triamcinolone ointment to be applied twice daily until the lesions resolved. At a one-month follow-up appointment, the patient indicated that her legs were now smooth and she was happy that she could shave them again. The FP told her that it would be a good idea to use emollients after bathing to keep the skin moist in order to prevent future episodes of nummular eczema.
Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Wah Y, Usatine R. Eczema. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013.
To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/
You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com
The FP made the presumptive diagnosis of nummular eczema, but recognized that a fungal infection and psoriasis were part of the differential diagnosis. He performed a potassium hydroxide (KOH) preparation, which was negative for hyphae and fungal elements. (See a video on how to perform a KOH preparation here: http://www.mdedge.com/jfponline/article/100603/dermatology/koh-preparation.) In order to explore whether this might be a case of guttate psoriasis, the FP asked about any preceding strep pharyngitis or other respiratory infections. The patient, however, had not had any preceding infections. The FP also checked her nails, scalp, and umbilicus for other signs of psoriasis, but found none. The FP was now confident in making a clinical diagnosis of nummular eczema (also known as nummular dermatitis).
Nummular eczema is a type of eczema characterized by circular or oval-shaped scaling plaques with well-defined borders. (“Nummus” is Latin for “coin.”) Nummular eczema produces multiple lesions that are most commonly found on the dorsa of the hands, arms, and legs.
Patients who have a history of atopic dermatitis are more likely to get nummular eczema even after they outgrow the atopic dermatitis. The 2 conditions involve problems with the barrier function of the skin, and emollients are helpful for the prevention and treatment of both.
In this case, the FP prescribed 0.1% triamcinolone ointment to be applied twice daily until the lesions resolved. At a one-month follow-up appointment, the patient indicated that her legs were now smooth and she was happy that she could shave them again. The FP told her that it would be a good idea to use emollients after bathing to keep the skin moist in order to prevent future episodes of nummular eczema.
Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Wah Y, Usatine R. Eczema. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013.
To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/
You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com
