Recently, like in other major cities, Phoenix had a flyover by the Blue Angels to honor frontline health care workers. My kids and I watched it. While I think the gesture is nice, in my mind it brings up questions about whether the money for it could have been better spent elsewhere. But that’s not the point of my column.

Watching the whole thing, I couldn’t help but think about my role in the crisis. While I have friends on the front lines, I’m certainly not there. I’m probably as close to back line as you can be without being retired.

This is simply the nature of my practice. I’m primarily outpatient. Inpatient consults are few and far between in the era of the neuro-hospitalist. I still see patients, both by video and in person. If someone wants to come in and see me, I’ll be available if I’m able.

I see a lot of conditions, but no one is going to a neurologist to be evaluated for COVID-19. Nor should they. Even though there are reports of neurological complications of the disease, none of them are outpatient issues or presenting symptoms.

I was asked if I’d volunteer to practice inpatient general medicine in a pinch, and my answer to that would have to be no. This isn’t cowardice, as one person accused me of. I’ve been to the hospital and seen patients since this started.

I’m no more an internist than I am an electrician. Like other neurologists of my era, I did a 1-year general medicine internship. For me, that was in 1993. I haven’t practiced it since, nor have I kept up on it except as it crosses into neurology.

A lot has changed in the last 27 years in my field alone. For me to jump back into general medicine after that time would likely do more harm than good to the patients I would see.

So I sit in my office doing what I always have: Trying to provide the best care I can to those who do need my services as a neurologist.

I may not be on the front line in our current crisis, but for those who seek my help I’m still front and center for them. And I will be until I retire.
 

Dr. Block has a solo neurology practice in Scottsdale, Ariz. He has no relevant disclosures.

Recently, like in other major cities, Phoenix had a flyover by the Blue Angels to honor frontline health care workers. My kids and I watched it. While I think the gesture is nice, in my mind it brings up questions about whether the money for it could have been better spent elsewhere. But that’s not the point of my column.

Watching the whole thing, I couldn’t help but think about my role in the crisis. While I have friends on the front lines, I’m certainly not there. I’m probably as close to back line as you can be without being retired.

This is simply the nature of my practice. I’m primarily outpatient. Inpatient consults are few and far between in the era of the neuro-hospitalist. I still see patients, both by video and in person. If someone wants to come in and see me, I’ll be available if I’m able.

I see a lot of conditions, but no one is going to a neurologist to be evaluated for COVID-19. Nor should they. Even though there are reports of neurological complications of the disease, none of them are outpatient issues or presenting symptoms.

I was asked if I’d volunteer to practice inpatient general medicine in a pinch, and my answer to that would have to be no. This isn’t cowardice, as one person accused me of. I’ve been to the hospital and seen patients since this started.

I’m no more an internist than I am an electrician. Like other neurologists of my era, I did a 1-year general medicine internship. For me, that was in 1993. I haven’t practiced it since, nor have I kept up on it except as it crosses into neurology.

A lot has changed in the last 27 years in my field alone. For me to jump back into general medicine after that time would likely do more harm than good to the patients I would see.

So I sit in my office doing what I always have: Trying to provide the best care I can to those who do need my services as a neurologist.

I may not be on the front line in our current crisis, but for those who seek my help I’m still front and center for them. And I will be until I retire.
 

Dr. Block has a solo neurology practice in Scottsdale, Ariz. He has no relevant disclosures.

Recently, like in other major cities, Phoenix had a flyover by the Blue Angels to honor frontline health care workers. My kids and I watched it. While I think the gesture is nice, in my mind it brings up questions about whether the money for it could have been better spent elsewhere. But that’s not the point of my column.

Watching the whole thing, I couldn’t help but think about my role in the crisis. While I have friends on the front lines, I’m certainly not there. I’m probably as close to back line as you can be without being retired.

This is simply the nature of my practice. I’m primarily outpatient. Inpatient consults are few and far between in the era of the neuro-hospitalist. I still see patients, both by video and in person. If someone wants to come in and see me, I’ll be available if I’m able.

I see a lot of conditions, but no one is going to a neurologist to be evaluated for COVID-19. Nor should they. Even though there are reports of neurological complications of the disease, none of them are outpatient issues or presenting symptoms.

I was asked if I’d volunteer to practice inpatient general medicine in a pinch, and my answer to that would have to be no. This isn’t cowardice, as one person accused me of. I’ve been to the hospital and seen patients since this started.

I’m no more an internist than I am an electrician. Like other neurologists of my era, I did a 1-year general medicine internship. For me, that was in 1993. I haven’t practiced it since, nor have I kept up on it except as it crosses into neurology.

A lot has changed in the last 27 years in my field alone. For me to jump back into general medicine after that time would likely do more harm than good to the patients I would see.

So I sit in my office doing what I always have: Trying to provide the best care I can to those who do need my services as a neurologist.

I may not be on the front line in our current crisis, but for those who seek my help I’m still front and center for them. And I will be until I retire.
 

Dr. Block has a solo neurology practice in Scottsdale, Ariz. He has no relevant disclosures.

Children whose parents are coping with illness and injuries were more likely to need medical treatment and prescriptions for gastrointestinal conditions, for which previous research already has indicated a brain-gut connection, an investigator said.

In a self-controlled case series using records from the Military Health System Data Repository, pediatric visits for disorders linked to gut-brain interactions were found to have increased 9% (incidence rate ratio, 1.09; 95% CI, 1.07-1.10) following a parent’s illness or injury, reported lead author Patrick Short, MD, of the Uniformed Services University of the Health Sciences, Bethesda, Md., said in an interview. The Military Health System Data Repository receives records from the Department of Defense’s global network of more than 260 medical facilities as well as outside health care organizations where military families are seen.

A secondary analysis done for this study found children of brain injured parents had 4% more postinjury visits for abdominal pain and 23% increased odds of antispasmodic prescription, compared with children whose parents had other physical injuries, Dr. Short said. He presented his research in an abstract released as part of the annual Digestive Disease Week, which was canceled because of COVID-19. The study focused on children aged 3-16 years with a parent who served in the military and was ill or injured between 2004 and 2014. Excluded from this research were records for children with diagnosed systemic or organic gastrointestinal disease, such as celiac disease.

The study used ICD-9 codes to identify outpatient visits for irritable bowel syndrome, abdominal pain, constipation, and fecal incontinence in the 2 years before and after parental injury or diagnosis of illness. Outpatient pharmacy records showed which of the children studied took laxatives and antispasmodics.

Parental injury or illness was defined by the placement of the children’s mothers and fathers on the injured, ill, or wounded file in the data repository. The data file generally covers people with conditions that severely limit their ability to do their usual jobs. These include traumatic brain injury, PTSD, amputation, shrapnel injury, and illnesses such as cancer.

There was a 7% increase in visits for constipation but fecal incontinence did not significantly change following parental illness or injury, Dr. Short said. But the odds of being prescribed an antispasmodic increased 23% following parents’ injuries and serious illnesses, while the odds for laxative prescription decreased by 5%.

The study highlights the potential physical impact of stress on children when families experience a crisis, Dr. Short said in an interview. Children may feel anxious about their parent’s health, while at the same time experiencing unavoidable disruption in family life because of an injury or illness.

“It impacts the day-to-day regimens and routines and decreases the family support,” Dr. Short said. “As humans we are limited in what we have to offer. When we are trying to take care of things on our own, it limits what we can give to people around us.”

The findings of this study should serve to remind physicians to alert parents that their children could experience worsening of GI conditions because of the stress of an ill or injured parent. They then can focus on securing help ahead of the time for the child, such as therapy, he said.

The next step in advancing on the research he prepared for DDW could be testing through prospective studies how well preventive measures such as family counseling work, Dr. Short said.

Dr. Short’s research adds to the growing body of evidence about the brain-gut connection, said Kara Gross Margolis, MD, a spokesperson for the American Gastroenterological Association. An associate professor of pediatrics at Columbia University Medical Center, New York, Dr. Margolis has published research on the brain-gut axis. Her lab focuses on the effects of neurotransmitters and inflammation on enteric nervous system development and function.

Physicians should take a broad view when treating children for functional GI illnesses. Behavioral therapy and antidepressants, for example, have been shown to help children with conditions such as irritable bowel syndrome and other functional gastrointestinal diseases, said Dr. Margolis.

“In a number of these cases, we not only have to treat the gut. We have to treat the brain as well,” Dr. Margolis said.

“When mental health issues are involved that impact the parents of these kids, You have to look at a family as an entire unit,” she added. “You not only treat the child for those symptoms, but you really have to look at how their parents can also be cared for so that their impact on their children will be positive as well.”

Research in the vein explored by Dr. Short will be important to remember as society works through the legacy of the COVID-19 pandemic, Dr. Margolis said. “We have huge numbers of families undergoing tremendous stress due to loss of jobs, health care, medical issues, and parental injury potentially from coronavirus.”

No outside funding was reported, and the study was covered through Uniformed Services University budget.

SOURCE: Short P et al. DDW 2020, Abstract 815.

Children whose parents are coping with illness and injuries were more likely to need medical treatment and prescriptions for gastrointestinal conditions, for which previous research already has indicated a brain-gut connection, an investigator said.

In a self-controlled case series using records from the Military Health System Data Repository, pediatric visits for disorders linked to gut-brain interactions were found to have increased 9% (incidence rate ratio, 1.09; 95% CI, 1.07-1.10) following a parent’s illness or injury, reported lead author Patrick Short, MD, of the Uniformed Services University of the Health Sciences, Bethesda, Md., said in an interview. The Military Health System Data Repository receives records from the Department of Defense’s global network of more than 260 medical facilities as well as outside health care organizations where military families are seen.

A secondary analysis done for this study found children of brain injured parents had 4% more postinjury visits for abdominal pain and 23% increased odds of antispasmodic prescription, compared with children whose parents had other physical injuries, Dr. Short said. He presented his research in an abstract released as part of the annual Digestive Disease Week, which was canceled because of COVID-19. The study focused on children aged 3-16 years with a parent who served in the military and was ill or injured between 2004 and 2014. Excluded from this research were records for children with diagnosed systemic or organic gastrointestinal disease, such as celiac disease.

The study used ICD-9 codes to identify outpatient visits for irritable bowel syndrome, abdominal pain, constipation, and fecal incontinence in the 2 years before and after parental injury or diagnosis of illness. Outpatient pharmacy records showed which of the children studied took laxatives and antispasmodics.

Parental injury or illness was defined by the placement of the children’s mothers and fathers on the injured, ill, or wounded file in the data repository. The data file generally covers people with conditions that severely limit their ability to do their usual jobs. These include traumatic brain injury, PTSD, amputation, shrapnel injury, and illnesses such as cancer.

There was a 7% increase in visits for constipation but fecal incontinence did not significantly change following parental illness or injury, Dr. Short said. But the odds of being prescribed an antispasmodic increased 23% following parents’ injuries and serious illnesses, while the odds for laxative prescription decreased by 5%.

The study highlights the potential physical impact of stress on children when families experience a crisis, Dr. Short said in an interview. Children may feel anxious about their parent’s health, while at the same time experiencing unavoidable disruption in family life because of an injury or illness.

“It impacts the day-to-day regimens and routines and decreases the family support,” Dr. Short said. “As humans we are limited in what we have to offer. When we are trying to take care of things on our own, it limits what we can give to people around us.”

The findings of this study should serve to remind physicians to alert parents that their children could experience worsening of GI conditions because of the stress of an ill or injured parent. They then can focus on securing help ahead of the time for the child, such as therapy, he said.

The next step in advancing on the research he prepared for DDW could be testing through prospective studies how well preventive measures such as family counseling work, Dr. Short said.

Dr. Short’s research adds to the growing body of evidence about the brain-gut connection, said Kara Gross Margolis, MD, a spokesperson for the American Gastroenterological Association. An associate professor of pediatrics at Columbia University Medical Center, New York, Dr. Margolis has published research on the brain-gut axis. Her lab focuses on the effects of neurotransmitters and inflammation on enteric nervous system development and function.

Physicians should take a broad view when treating children for functional GI illnesses. Behavioral therapy and antidepressants, for example, have been shown to help children with conditions such as irritable bowel syndrome and other functional gastrointestinal diseases, said Dr. Margolis.

“In a number of these cases, we not only have to treat the gut. We have to treat the brain as well,” Dr. Margolis said.

“When mental health issues are involved that impact the parents of these kids, You have to look at a family as an entire unit,” she added. “You not only treat the child for those symptoms, but you really have to look at how their parents can also be cared for so that their impact on their children will be positive as well.”

Research in the vein explored by Dr. Short will be important to remember as society works through the legacy of the COVID-19 pandemic, Dr. Margolis said. “We have huge numbers of families undergoing tremendous stress due to loss of jobs, health care, medical issues, and parental injury potentially from coronavirus.”

No outside funding was reported, and the study was covered through Uniformed Services University budget.

SOURCE: Short P et al. DDW 2020, Abstract 815.

Children whose parents are coping with illness and injuries were more likely to need medical treatment and prescriptions for gastrointestinal conditions, for which previous research already has indicated a brain-gut connection, an investigator said.

In a self-controlled case series using records from the Military Health System Data Repository, pediatric visits for disorders linked to gut-brain interactions were found to have increased 9% (incidence rate ratio, 1.09; 95% CI, 1.07-1.10) following a parent’s illness or injury, reported lead author Patrick Short, MD, of the Uniformed Services University of the Health Sciences, Bethesda, Md., said in an interview. The Military Health System Data Repository receives records from the Department of Defense’s global network of more than 260 medical facilities as well as outside health care organizations where military families are seen.

A secondary analysis done for this study found children of brain injured parents had 4% more postinjury visits for abdominal pain and 23% increased odds of antispasmodic prescription, compared with children whose parents had other physical injuries, Dr. Short said. He presented his research in an abstract released as part of the annual Digestive Disease Week, which was canceled because of COVID-19. The study focused on children aged 3-16 years with a parent who served in the military and was ill or injured between 2004 and 2014. Excluded from this research were records for children with diagnosed systemic or organic gastrointestinal disease, such as celiac disease.

The study used ICD-9 codes to identify outpatient visits for irritable bowel syndrome, abdominal pain, constipation, and fecal incontinence in the 2 years before and after parental injury or diagnosis of illness. Outpatient pharmacy records showed which of the children studied took laxatives and antispasmodics.

Parental injury or illness was defined by the placement of the children’s mothers and fathers on the injured, ill, or wounded file in the data repository. The data file generally covers people with conditions that severely limit their ability to do their usual jobs. These include traumatic brain injury, PTSD, amputation, shrapnel injury, and illnesses such as cancer.

There was a 7% increase in visits for constipation but fecal incontinence did not significantly change following parental illness or injury, Dr. Short said. But the odds of being prescribed an antispasmodic increased 23% following parents’ injuries and serious illnesses, while the odds for laxative prescription decreased by 5%.

The study highlights the potential physical impact of stress on children when families experience a crisis, Dr. Short said in an interview. Children may feel anxious about their parent’s health, while at the same time experiencing unavoidable disruption in family life because of an injury or illness.

“It impacts the day-to-day regimens and routines and decreases the family support,” Dr. Short said. “As humans we are limited in what we have to offer. When we are trying to take care of things on our own, it limits what we can give to people around us.”

The findings of this study should serve to remind physicians to alert parents that their children could experience worsening of GI conditions because of the stress of an ill or injured parent. They then can focus on securing help ahead of the time for the child, such as therapy, he said.

The next step in advancing on the research he prepared for DDW could be testing through prospective studies how well preventive measures such as family counseling work, Dr. Short said.

Dr. Short’s research adds to the growing body of evidence about the brain-gut connection, said Kara Gross Margolis, MD, a spokesperson for the American Gastroenterological Association. An associate professor of pediatrics at Columbia University Medical Center, New York, Dr. Margolis has published research on the brain-gut axis. Her lab focuses on the effects of neurotransmitters and inflammation on enteric nervous system development and function.

Physicians should take a broad view when treating children for functional GI illnesses. Behavioral therapy and antidepressants, for example, have been shown to help children with conditions such as irritable bowel syndrome and other functional gastrointestinal diseases, said Dr. Margolis.

“In a number of these cases, we not only have to treat the gut. We have to treat the brain as well,” Dr. Margolis said.

“When mental health issues are involved that impact the parents of these kids, You have to look at a family as an entire unit,” she added. “You not only treat the child for those symptoms, but you really have to look at how their parents can also be cared for so that their impact on their children will be positive as well.”

Research in the vein explored by Dr. Short will be important to remember as society works through the legacy of the COVID-19 pandemic, Dr. Margolis said. “We have huge numbers of families undergoing tremendous stress due to loss of jobs, health care, medical issues, and parental injury potentially from coronavirus.”

No outside funding was reported, and the study was covered through Uniformed Services University budget.

SOURCE: Short P et al. DDW 2020, Abstract 815.

Yesterday during an office visit I was adjusting my mask when a patient suddenly said, “What if this is the new normal? What if we still have to wear masks years from now?”

An interesting thought. That might even be the case. I mean, the COVID-19 pandemic definitely has changed our world. On the other hand, there are far worse things to have to do.

Masks, to some extent, have already become a part of our society, I see more people out and about with them than without. Like lunchboxes, they’ve transitioned from utilitarian to fashion statements. I see Darth Vader, Batman, Hello Kitty, Pokemon, and many other characters on them.

Humans have, after all, adapted to wearing all kinds of things. At some point our ancestors discovered they could walk around outside more comfortably with a covering on their feet. Then they discovered that socks prevent chafing. Now shoes and socks are worn worldwide, available for many different purposes in varied colors, styles, and cultures.

Why should masks be any different? Just because they’re new doesn’t mean they’re bad.

Obviously, I’m exaggerating. I don’t want to wear a mask full time, either. They’re hot and uncomfortable and, for people with certain respiratory issues, impossible. I live in Phoenix and I definitely don’t want to go through one of our summers wearing a face mask.

But at the same time, while masks are no guarantee against viral spread, they certainly help reduce it. This makes me wonder when we’ll start to phase them out. The virus isn’t going anywhere, so the breaking point will be when there’s either an effective vaccine administered to most of the population, or enough people have had the virus that herd immunity takes effect.

Until then, I have no problem with wearing a mask and asking patients who can to please do so when they come in. I see a lot of people who are elderly and/or immune suppressed. I don’t want them to get sick. Or me. Or my family.

If wearing a mask through the Phoenix summer is a sacrifice that will lead to better health for all, it’s not a big one in the grand scheme of things.
 

Dr. Block has a solo neurology practice in Scottsdale, Ariz. He has no relevant disclosures.

Yesterday during an office visit I was adjusting my mask when a patient suddenly said, “What if this is the new normal? What if we still have to wear masks years from now?”

An interesting thought. That might even be the case. I mean, the COVID-19 pandemic definitely has changed our world. On the other hand, there are far worse things to have to do.

Masks, to some extent, have already become a part of our society, I see more people out and about with them than without. Like lunchboxes, they’ve transitioned from utilitarian to fashion statements. I see Darth Vader, Batman, Hello Kitty, Pokemon, and many other characters on them.

Humans have, after all, adapted to wearing all kinds of things. At some point our ancestors discovered they could walk around outside more comfortably with a covering on their feet. Then they discovered that socks prevent chafing. Now shoes and socks are worn worldwide, available for many different purposes in varied colors, styles, and cultures.

Why should masks be any different? Just because they’re new doesn’t mean they’re bad.

Obviously, I’m exaggerating. I don’t want to wear a mask full time, either. They’re hot and uncomfortable and, for people with certain respiratory issues, impossible. I live in Phoenix and I definitely don’t want to go through one of our summers wearing a face mask.

But at the same time, while masks are no guarantee against viral spread, they certainly help reduce it. This makes me wonder when we’ll start to phase them out. The virus isn’t going anywhere, so the breaking point will be when there’s either an effective vaccine administered to most of the population, or enough people have had the virus that herd immunity takes effect.

Until then, I have no problem with wearing a mask and asking patients who can to please do so when they come in. I see a lot of people who are elderly and/or immune suppressed. I don’t want them to get sick. Or me. Or my family.

If wearing a mask through the Phoenix summer is a sacrifice that will lead to better health for all, it’s not a big one in the grand scheme of things.
 

Dr. Block has a solo neurology practice in Scottsdale, Ariz. He has no relevant disclosures.

Yesterday during an office visit I was adjusting my mask when a patient suddenly said, “What if this is the new normal? What if we still have to wear masks years from now?”

An interesting thought. That might even be the case. I mean, the COVID-19 pandemic definitely has changed our world. On the other hand, there are far worse things to have to do.

Masks, to some extent, have already become a part of our society, I see more people out and about with them than without. Like lunchboxes, they’ve transitioned from utilitarian to fashion statements. I see Darth Vader, Batman, Hello Kitty, Pokemon, and many other characters on them.

Humans have, after all, adapted to wearing all kinds of things. At some point our ancestors discovered they could walk around outside more comfortably with a covering on their feet. Then they discovered that socks prevent chafing. Now shoes and socks are worn worldwide, available for many different purposes in varied colors, styles, and cultures.

Why should masks be any different? Just because they’re new doesn’t mean they’re bad.

Obviously, I’m exaggerating. I don’t want to wear a mask full time, either. They’re hot and uncomfortable and, for people with certain respiratory issues, impossible. I live in Phoenix and I definitely don’t want to go through one of our summers wearing a face mask.

But at the same time, while masks are no guarantee against viral spread, they certainly help reduce it. This makes me wonder when we’ll start to phase them out. The virus isn’t going anywhere, so the breaking point will be when there’s either an effective vaccine administered to most of the population, or enough people have had the virus that herd immunity takes effect.

Until then, I have no problem with wearing a mask and asking patients who can to please do so when they come in. I see a lot of people who are elderly and/or immune suppressed. I don’t want them to get sick. Or me. Or my family.

If wearing a mask through the Phoenix summer is a sacrifice that will lead to better health for all, it’s not a big one in the grand scheme of things.
 

Dr. Block has a solo neurology practice in Scottsdale, Ariz. He has no relevant disclosures.

Sickle cell disease is associated with worse long-term bone health than that of the general population, and SCD patients are more likely to experience vitamin D [25(OH)D] deficiency. Oral vitamin D3 supplementation can achieve protective levels in children with sickle cell disease, and a daily dose was able to achieved optimal blood levels, according to a report published online in Bone.

The researchers performed a prospective, longitudinal, single-center study of 80 children with SCD. They collected demographic, clinical, and management data, as well as 25(OH)D levels. Bone densitometries (DXA) were also collected.

Among the 80 patients were included in the analysis, there were significant differences between the means of 25(OH)D levels based on whether the patient started prophylactic treatment as an infant or not (35.7 vs. 27.9 ng/mL, respectively [P = .014]), according to the researchers.

They also found that, in multivariate analysis, an oral 800 IU daily dose of vitamin D3 was shown to be a protective factor (P = .044) in reaching optimal 25(OH)D blood levels (≥ 30 ng/mL).

Kaplan-Meier analysis showed that those patients younger than 10 years of age reached optimal levels significantly earlier than older patients when on supplementation (P = .002), as did those patients who were not being treated with hydroxyurea (P = .039), the researchers wrote.

Significant differences were seen between the mean bone mineral density in both DXAs performed when comparing suboptimal vs. optimal blood levels of 25(OH)D (0.54 g/cm² vs. 0.64 g/cm2, respectively, P = .001), for the initial DXA, and for the most recent DXA (0.59 g/cm² vs. 0.77 g/cm², respectively, P = .044). “VitD3 prophylaxis is a safe practice in SCD. It is important to start this prophylactic treatment when the child is an infant. The daily regimen with 800 IU could be more effective for reaching levels ≥ 30 ng/mL, and, especially in preadolescent and adolescent patients, we should raise awareness about the importance of good bone health,” the authors concluded.

The authors reported that they had no conflicts of interest.

mlesney@mdedge.com

SOURCE: Garrido C et al. Bone. 2020;133: doi.org/10.1016/j.bone.2020.115228.

Sickle cell disease is associated with worse long-term bone health than that of the general population, and SCD patients are more likely to experience vitamin D [25(OH)D] deficiency. Oral vitamin D3 supplementation can achieve protective levels in children with sickle cell disease, and a daily dose was able to achieved optimal blood levels, according to a report published online in Bone.

The researchers performed a prospective, longitudinal, single-center study of 80 children with SCD. They collected demographic, clinical, and management data, as well as 25(OH)D levels. Bone densitometries (DXA) were also collected.

Among the 80 patients were included in the analysis, there were significant differences between the means of 25(OH)D levels based on whether the patient started prophylactic treatment as an infant or not (35.7 vs. 27.9 ng/mL, respectively [P = .014]), according to the researchers.

They also found that, in multivariate analysis, an oral 800 IU daily dose of vitamin D3 was shown to be a protective factor (P = .044) in reaching optimal 25(OH)D blood levels (≥ 30 ng/mL).

Kaplan-Meier analysis showed that those patients younger than 10 years of age reached optimal levels significantly earlier than older patients when on supplementation (P = .002), as did those patients who were not being treated with hydroxyurea (P = .039), the researchers wrote.

Significant differences were seen between the mean bone mineral density in both DXAs performed when comparing suboptimal vs. optimal blood levels of 25(OH)D (0.54 g/cm² vs. 0.64 g/cm2, respectively, P = .001), for the initial DXA, and for the most recent DXA (0.59 g/cm² vs. 0.77 g/cm², respectively, P = .044). “VitD3 prophylaxis is a safe practice in SCD. It is important to start this prophylactic treatment when the child is an infant. The daily regimen with 800 IU could be more effective for reaching levels ≥ 30 ng/mL, and, especially in preadolescent and adolescent patients, we should raise awareness about the importance of good bone health,” the authors concluded.

The authors reported that they had no conflicts of interest.

mlesney@mdedge.com

SOURCE: Garrido C et al. Bone. 2020;133: doi.org/10.1016/j.bone.2020.115228.

Sickle cell disease is associated with worse long-term bone health than that of the general population, and SCD patients are more likely to experience vitamin D [25(OH)D] deficiency. Oral vitamin D3 supplementation can achieve protective levels in children with sickle cell disease, and a daily dose was able to achieved optimal blood levels, according to a report published online in Bone.

The researchers performed a prospective, longitudinal, single-center study of 80 children with SCD. They collected demographic, clinical, and management data, as well as 25(OH)D levels. Bone densitometries (DXA) were also collected.

Among the 80 patients were included in the analysis, there were significant differences between the means of 25(OH)D levels based on whether the patient started prophylactic treatment as an infant or not (35.7 vs. 27.9 ng/mL, respectively [P = .014]), according to the researchers.

They also found that, in multivariate analysis, an oral 800 IU daily dose of vitamin D3 was shown to be a protective factor (P = .044) in reaching optimal 25(OH)D blood levels (≥ 30 ng/mL).

Kaplan-Meier analysis showed that those patients younger than 10 years of age reached optimal levels significantly earlier than older patients when on supplementation (P = .002), as did those patients who were not being treated with hydroxyurea (P = .039), the researchers wrote.

Significant differences were seen between the mean bone mineral density in both DXAs performed when comparing suboptimal vs. optimal blood levels of 25(OH)D (0.54 g/cm² vs. 0.64 g/cm2, respectively, P = .001), for the initial DXA, and for the most recent DXA (0.59 g/cm² vs. 0.77 g/cm², respectively, P = .044). “VitD3 prophylaxis is a safe practice in SCD. It is important to start this prophylactic treatment when the child is an infant. The daily regimen with 800 IU could be more effective for reaching levels ≥ 30 ng/mL, and, especially in preadolescent and adolescent patients, we should raise awareness about the importance of good bone health,” the authors concluded.

The authors reported that they had no conflicts of interest.

mlesney@mdedge.com

SOURCE: Garrido C et al. Bone. 2020;133: doi.org/10.1016/j.bone.2020.115228.

Two MEK inhibitors were tested against recurrent low-grade serous carcinomas of the ovaries, fallopian tubes, or peritoneum, but only one inhibitor offered clinical benefit over standard care, investigators from two randomized trials reported.

Trametinib improved progression-free survival (PFS) when compared with standard care, while binimetinib conferred no PFS benefit.

In a phase 2/3 trial, the median PFS was 13 months for patients treated with trametinib and 7.2 months for patients who received an aromatase inhibitor or chemotherapy (P < .0001).

“Our findings suggest that trametinib represents a new standard-of-care treatment option for women with recurrent low-grade serous carcinoma,” said investigator David M. Gershenson, MD, of the University of Texas MD Anderson Cancer Center in Houston.

In contrast, in the phase 3 MILO/ENGOT-ov11 trial, there was no significant difference in PFS between patients treated with binimetinib and those who received physician’s choice of chemotherapy. The median PFS was 11.2 months with binimetinib and 14.1 months with chemotherapy (P = .752).

“Although this study did not meet its primary endpoint, binimetinib showed activity in low-grade serous ovarian cancer across the efficacy endpoints evaluated, with a response rate of 24% and a median PFS of 11.2 months on updated analysis. Chemotherapy responses were better than predicted, based on historical retrospective data,” said investigator Rachel N. Grisham, MD, of Memorial Sloan Kettering Cancer Center in New York.

The binimetinib trial and the trametinib trial were both discussed during a webinar on rare tumors covering research slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. The meeting was canceled because of the COVID-19 pandemic.
 

Chemoresistant cancers

Low-grade serous ovarian or peritoneal cancers are rare, accounting for only 5% to 10% of all serous cancers, Dr. Gershenson noted.

“[Low-grade serous cancers are] characterized by alterations in the MAP kinase pathway, as well as relative chemoresistance, and prolonged overall survival compared to high-grade serous cancers. Because of this subtype’s relative chemoresistance, the search for novel therapeutics has predominated over the last decade or so,” he said.

MEK inhibitors interfere with the MEK1 and MEK2 enzymes in the MAPK pathway. Alterations in MAPK, especially in KRAS and BRAF proteins, are found in 30%-60% of low-grade serous carcinomas, providing the rationale for MEK inhibitors in these rare malignancies.
 

Trametinib study

In a phase 2/3 study, Dr. Gershenson and colleagues enrolled 260 patients with recurrent, low-grade serous carcinoma of the ovary or peritoneum. Patients were randomized to receive either trametinib at 2 mg daily continuously until progression (n = 130) or standard care (n = 130).

Standard care consisted of one of the following: letrozole at 2.5 mg daily; pegylated liposomal doxorubicin at 40-50 mg IV every 28 days; weekly paclitaxel at 80 mg/m² for 3 out of 4 weeks; tamoxifen at 20 mg twice daily; or topotecan at 4 mg/m² on days 1, 8, and 15 every 28 days. Patients randomized to standard care could be crossed over to trametinib at progression.

All patients had at least one prior line of platinum-based chemotherapy, and nearly half had three or more prior lines of therapy. The median age was 56.6 years in the trametinib arm and 55.3 years in the control arm.

At a median follow-up of 31.4 months, median PFS, the primary endpoint, was 13 months with trametinib vs. 7.2 months with standard care. The hazard ratio (HR) for progression on trametinib was 0.48 (P < .0001).

The overall response rates were 26.2% in the trametinib arm and 6.2% in the standard care arm. The odds ratio for response on trametinib was 5.4 (P < .0001).

For 88 patients who crossed over to trametinib, the median PFS was 10.8 months, and the overall response rate was 15%.

Trametinib was also associated with a significantly longer response duration, at a median of 13.6 months, compared with 5.9 months for standard care (P value not shown).

The median overall survival was 37 months with trametinib and 29.2 months with standard care, with an HR favoring trametinib of 0.75, although this just missed statistical significance (P = .054). Dr. Gershenson pointed out that the overall survival in the standard care arm included patients who had been crossed over to trametinib.

Grade 3 or greater adverse events included hematologic toxicities in 13.4% of patients on trametinib and 9.4% on standard care; gastrointestinal toxicity in 27.6% and 29%, respectively; skin toxicities in 15% and 3.9%, respectively; and vascular toxicities in 18.9% and 8.6%, respectively.
 

Binimetinib study

The phase 3 MILO/ENGOT-ov11 study enrolled 341 patients with low-grade serous carcinomas of the ovaries, fallopian tubes, or peritoneum. Patients were randomized on a 2:1 basis to receive either binimetinib at 45 mg twice daily (n = 228) or physician’s choice of chemotherapy (n = 113). Chemotherapy consisted of pegylated liposomal doxorubicin at 40 mg/m² on day 1 of each 28-day cycle; paclitaxel at 80 mg/m² on days 1, 8, and 15 of each 28-day cycle; or topotecan at 1.25 mg/m² IV on days 1-5 of each 21-day cycle.

The efficacy analysis included 227 patients assigned to binimetinib and 106 assigned to chemotherapy.

A planned interim analysis was performed in 2016 after the first 303 patients were enrolled. At that time, the median PFS by blinded central review was 9.1 months in the binimetinib arm and 10.6 months in the physician’s choice arm (HR, 1.21; P = .807), so the trial was halted early for futility. Patients on active treatment at the time could continue until progression and were followed by local radiology.

At the interim analysis, secondary endpoints were also similar between the arms. The overall response rate was 16% in the binimetinib arm and 13% in the chemotherapy arm.

The most common grade 3 or greater adverse events with binimetinib were blood creatinine phosphokinase increase (26%) and vomiting (10%).

Dr. Grisham also reported updated follow-up results through January 2019.

The median PFS in the updated analysis was 11.2 months with the MEK inhibitor and 14.1 months with chemotherapy, a difference that was not statistically significant (HR, 1.12; P = .752). Updated overall response rates were the same in both arms, at 24%.

A post hoc molecular analysis of 215 patients suggested a possible association between KRAS mutation and response to binimetinib.
 

Two MEKs, one ‘meh’

Discussant Jubilee Brown, MD, of the Levine Cancer Institute at Atrium Health in Charlotte, N.C., said that “with a 2% to 5% chance of response in patients with low-grade serous ovarian cancer, there is a low bar for any compound to demonstrate success.”

Regarding the MILO/ENGOT-ov11 trial, she noted that “this study did not meet its primary endpoint, but perhaps the endpoint is not reflective of the importance of the study.”

A different outcome might have occurred had investigators stratified patients by KRAS status upfront, comparing patients with KRAS mutations treated with binimetinib to KRAS wild-type patients treated with either a MEK inhibitor or physician’s choice of care, Dr. Brown said.

She agreed with the assertion by Dr. Gershenson and colleagues that improved PFS qualifies trametinib to be considered a new option for standard care, ”especially in a rare tumor setting with limited options. This is a huge win for patients.”

The trametinib study was sponsored by NRG Oncology and the UK National Cancer Research Institute. Dr. Gershenson disclosed relationships with NRG Oncology, Genentech, Novartis, Elsevier, and UpToDate, as well as stock in several companies.

The binimetinib study was sponsored by Pfizer. Dr. Grisham disclosed relationships with Clovis, Regeneron, Mateon, Amgen, Abbvie, OncLive, PRIME, MCM, and Medscape. MDedge News and Medscape are owned by the same parent organization.

Dr. Brown disclosed consulting for Biodesix, Caris, Clovis, Genentech, Invitae, Janssen, Olympus, OncLive, and Tempus.

SOURCE: Gershenson DM et al. SGO 2020, Abstract 42; Grisham RN et al. SGO 2020, Abstract 41.

Two MEK inhibitors were tested against recurrent low-grade serous carcinomas of the ovaries, fallopian tubes, or peritoneum, but only one inhibitor offered clinical benefit over standard care, investigators from two randomized trials reported.

Trametinib improved progression-free survival (PFS) when compared with standard care, while binimetinib conferred no PFS benefit.

In a phase 2/3 trial, the median PFS was 13 months for patients treated with trametinib and 7.2 months for patients who received an aromatase inhibitor or chemotherapy (P < .0001).

“Our findings suggest that trametinib represents a new standard-of-care treatment option for women with recurrent low-grade serous carcinoma,” said investigator David M. Gershenson, MD, of the University of Texas MD Anderson Cancer Center in Houston.

In contrast, in the phase 3 MILO/ENGOT-ov11 trial, there was no significant difference in PFS between patients treated with binimetinib and those who received physician’s choice of chemotherapy. The median PFS was 11.2 months with binimetinib and 14.1 months with chemotherapy (P = .752).

“Although this study did not meet its primary endpoint, binimetinib showed activity in low-grade serous ovarian cancer across the efficacy endpoints evaluated, with a response rate of 24% and a median PFS of 11.2 months on updated analysis. Chemotherapy responses were better than predicted, based on historical retrospective data,” said investigator Rachel N. Grisham, MD, of Memorial Sloan Kettering Cancer Center in New York.

The binimetinib trial and the trametinib trial were both discussed during a webinar on rare tumors covering research slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. The meeting was canceled because of the COVID-19 pandemic.
 

Chemoresistant cancers

Low-grade serous ovarian or peritoneal cancers are rare, accounting for only 5% to 10% of all serous cancers, Dr. Gershenson noted.

“[Low-grade serous cancers are] characterized by alterations in the MAP kinase pathway, as well as relative chemoresistance, and prolonged overall survival compared to high-grade serous cancers. Because of this subtype’s relative chemoresistance, the search for novel therapeutics has predominated over the last decade or so,” he said.

MEK inhibitors interfere with the MEK1 and MEK2 enzymes in the MAPK pathway. Alterations in MAPK, especially in KRAS and BRAF proteins, are found in 30%-60% of low-grade serous carcinomas, providing the rationale for MEK inhibitors in these rare malignancies.
 

Trametinib study

In a phase 2/3 study, Dr. Gershenson and colleagues enrolled 260 patients with recurrent, low-grade serous carcinoma of the ovary or peritoneum. Patients were randomized to receive either trametinib at 2 mg daily continuously until progression (n = 130) or standard care (n = 130).

Standard care consisted of one of the following: letrozole at 2.5 mg daily; pegylated liposomal doxorubicin at 40-50 mg IV every 28 days; weekly paclitaxel at 80 mg/m² for 3 out of 4 weeks; tamoxifen at 20 mg twice daily; or topotecan at 4 mg/m² on days 1, 8, and 15 every 28 days. Patients randomized to standard care could be crossed over to trametinib at progression.

All patients had at least one prior line of platinum-based chemotherapy, and nearly half had three or more prior lines of therapy. The median age was 56.6 years in the trametinib arm and 55.3 years in the control arm.

At a median follow-up of 31.4 months, median PFS, the primary endpoint, was 13 months with trametinib vs. 7.2 months with standard care. The hazard ratio (HR) for progression on trametinib was 0.48 (P < .0001).

The overall response rates were 26.2% in the trametinib arm and 6.2% in the standard care arm. The odds ratio for response on trametinib was 5.4 (P < .0001).

For 88 patients who crossed over to trametinib, the median PFS was 10.8 months, and the overall response rate was 15%.

Trametinib was also associated with a significantly longer response duration, at a median of 13.6 months, compared with 5.9 months for standard care (P value not shown).

The median overall survival was 37 months with trametinib and 29.2 months with standard care, with an HR favoring trametinib of 0.75, although this just missed statistical significance (P = .054). Dr. Gershenson pointed out that the overall survival in the standard care arm included patients who had been crossed over to trametinib.

Grade 3 or greater adverse events included hematologic toxicities in 13.4% of patients on trametinib and 9.4% on standard care; gastrointestinal toxicity in 27.6% and 29%, respectively; skin toxicities in 15% and 3.9%, respectively; and vascular toxicities in 18.9% and 8.6%, respectively.
 

Binimetinib study

The phase 3 MILO/ENGOT-ov11 study enrolled 341 patients with low-grade serous carcinomas of the ovaries, fallopian tubes, or peritoneum. Patients were randomized on a 2:1 basis to receive either binimetinib at 45 mg twice daily (n = 228) or physician’s choice of chemotherapy (n = 113). Chemotherapy consisted of pegylated liposomal doxorubicin at 40 mg/m² on day 1 of each 28-day cycle; paclitaxel at 80 mg/m² on days 1, 8, and 15 of each 28-day cycle; or topotecan at 1.25 mg/m² IV on days 1-5 of each 21-day cycle.

The efficacy analysis included 227 patients assigned to binimetinib and 106 assigned to chemotherapy.

A planned interim analysis was performed in 2016 after the first 303 patients were enrolled. At that time, the median PFS by blinded central review was 9.1 months in the binimetinib arm and 10.6 months in the physician’s choice arm (HR, 1.21; P = .807), so the trial was halted early for futility. Patients on active treatment at the time could continue until progression and were followed by local radiology.

At the interim analysis, secondary endpoints were also similar between the arms. The overall response rate was 16% in the binimetinib arm and 13% in the chemotherapy arm.

The most common grade 3 or greater adverse events with binimetinib were blood creatinine phosphokinase increase (26%) and vomiting (10%).

Dr. Grisham also reported updated follow-up results through January 2019.

The median PFS in the updated analysis was 11.2 months with the MEK inhibitor and 14.1 months with chemotherapy, a difference that was not statistically significant (HR, 1.12; P = .752). Updated overall response rates were the same in both arms, at 24%.

A post hoc molecular analysis of 215 patients suggested a possible association between KRAS mutation and response to binimetinib.
 

Two MEKs, one ‘meh’

Discussant Jubilee Brown, MD, of the Levine Cancer Institute at Atrium Health in Charlotte, N.C., said that “with a 2% to 5% chance of response in patients with low-grade serous ovarian cancer, there is a low bar for any compound to demonstrate success.”

Regarding the MILO/ENGOT-ov11 trial, she noted that “this study did not meet its primary endpoint, but perhaps the endpoint is not reflective of the importance of the study.”

A different outcome might have occurred had investigators stratified patients by KRAS status upfront, comparing patients with KRAS mutations treated with binimetinib to KRAS wild-type patients treated with either a MEK inhibitor or physician’s choice of care, Dr. Brown said.

She agreed with the assertion by Dr. Gershenson and colleagues that improved PFS qualifies trametinib to be considered a new option for standard care, ”especially in a rare tumor setting with limited options. This is a huge win for patients.”

The trametinib study was sponsored by NRG Oncology and the UK National Cancer Research Institute. Dr. Gershenson disclosed relationships with NRG Oncology, Genentech, Novartis, Elsevier, and UpToDate, as well as stock in several companies.

The binimetinib study was sponsored by Pfizer. Dr. Grisham disclosed relationships with Clovis, Regeneron, Mateon, Amgen, Abbvie, OncLive, PRIME, MCM, and Medscape. MDedge News and Medscape are owned by the same parent organization.

Dr. Brown disclosed consulting for Biodesix, Caris, Clovis, Genentech, Invitae, Janssen, Olympus, OncLive, and Tempus.

SOURCE: Gershenson DM et al. SGO 2020, Abstract 42; Grisham RN et al. SGO 2020, Abstract 41.

Two MEK inhibitors were tested against recurrent low-grade serous carcinomas of the ovaries, fallopian tubes, or peritoneum, but only one inhibitor offered clinical benefit over standard care, investigators from two randomized trials reported.

Trametinib improved progression-free survival (PFS) when compared with standard care, while binimetinib conferred no PFS benefit.

In a phase 2/3 trial, the median PFS was 13 months for patients treated with trametinib and 7.2 months for patients who received an aromatase inhibitor or chemotherapy (P < .0001).

“Our findings suggest that trametinib represents a new standard-of-care treatment option for women with recurrent low-grade serous carcinoma,” said investigator David M. Gershenson, MD, of the University of Texas MD Anderson Cancer Center in Houston.

In contrast, in the phase 3 MILO/ENGOT-ov11 trial, there was no significant difference in PFS between patients treated with binimetinib and those who received physician’s choice of chemotherapy. The median PFS was 11.2 months with binimetinib and 14.1 months with chemotherapy (P = .752).

“Although this study did not meet its primary endpoint, binimetinib showed activity in low-grade serous ovarian cancer across the efficacy endpoints evaluated, with a response rate of 24% and a median PFS of 11.2 months on updated analysis. Chemotherapy responses were better than predicted, based on historical retrospective data,” said investigator Rachel N. Grisham, MD, of Memorial Sloan Kettering Cancer Center in New York.

The binimetinib trial and the trametinib trial were both discussed during a webinar on rare tumors covering research slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. The meeting was canceled because of the COVID-19 pandemic.
 

Chemoresistant cancers

Low-grade serous ovarian or peritoneal cancers are rare, accounting for only 5% to 10% of all serous cancers, Dr. Gershenson noted.

“[Low-grade serous cancers are] characterized by alterations in the MAP kinase pathway, as well as relative chemoresistance, and prolonged overall survival compared to high-grade serous cancers. Because of this subtype’s relative chemoresistance, the search for novel therapeutics has predominated over the last decade or so,” he said.

MEK inhibitors interfere with the MEK1 and MEK2 enzymes in the MAPK pathway. Alterations in MAPK, especially in KRAS and BRAF proteins, are found in 30%-60% of low-grade serous carcinomas, providing the rationale for MEK inhibitors in these rare malignancies.
 

Trametinib study

In a phase 2/3 study, Dr. Gershenson and colleagues enrolled 260 patients with recurrent, low-grade serous carcinoma of the ovary or peritoneum. Patients were randomized to receive either trametinib at 2 mg daily continuously until progression (n = 130) or standard care (n = 130).

Standard care consisted of one of the following: letrozole at 2.5 mg daily; pegylated liposomal doxorubicin at 40-50 mg IV every 28 days; weekly paclitaxel at 80 mg/m² for 3 out of 4 weeks; tamoxifen at 20 mg twice daily; or topotecan at 4 mg/m² on days 1, 8, and 15 every 28 days. Patients randomized to standard care could be crossed over to trametinib at progression.

All patients had at least one prior line of platinum-based chemotherapy, and nearly half had three or more prior lines of therapy. The median age was 56.6 years in the trametinib arm and 55.3 years in the control arm.

At a median follow-up of 31.4 months, median PFS, the primary endpoint, was 13 months with trametinib vs. 7.2 months with standard care. The hazard ratio (HR) for progression on trametinib was 0.48 (P < .0001).

The overall response rates were 26.2% in the trametinib arm and 6.2% in the standard care arm. The odds ratio for response on trametinib was 5.4 (P < .0001).

For 88 patients who crossed over to trametinib, the median PFS was 10.8 months, and the overall response rate was 15%.

Trametinib was also associated with a significantly longer response duration, at a median of 13.6 months, compared with 5.9 months for standard care (P value not shown).

The median overall survival was 37 months with trametinib and 29.2 months with standard care, with an HR favoring trametinib of 0.75, although this just missed statistical significance (P = .054). Dr. Gershenson pointed out that the overall survival in the standard care arm included patients who had been crossed over to trametinib.

Grade 3 or greater adverse events included hematologic toxicities in 13.4% of patients on trametinib and 9.4% on standard care; gastrointestinal toxicity in 27.6% and 29%, respectively; skin toxicities in 15% and 3.9%, respectively; and vascular toxicities in 18.9% and 8.6%, respectively.
 

Binimetinib study

The phase 3 MILO/ENGOT-ov11 study enrolled 341 patients with low-grade serous carcinomas of the ovaries, fallopian tubes, or peritoneum. Patients were randomized on a 2:1 basis to receive either binimetinib at 45 mg twice daily (n = 228) or physician’s choice of chemotherapy (n = 113). Chemotherapy consisted of pegylated liposomal doxorubicin at 40 mg/m² on day 1 of each 28-day cycle; paclitaxel at 80 mg/m² on days 1, 8, and 15 of each 28-day cycle; or topotecan at 1.25 mg/m² IV on days 1-5 of each 21-day cycle.

The efficacy analysis included 227 patients assigned to binimetinib and 106 assigned to chemotherapy.

A planned interim analysis was performed in 2016 after the first 303 patients were enrolled. At that time, the median PFS by blinded central review was 9.1 months in the binimetinib arm and 10.6 months in the physician’s choice arm (HR, 1.21; P = .807), so the trial was halted early for futility. Patients on active treatment at the time could continue until progression and were followed by local radiology.

At the interim analysis, secondary endpoints were also similar between the arms. The overall response rate was 16% in the binimetinib arm and 13% in the chemotherapy arm.

The most common grade 3 or greater adverse events with binimetinib were blood creatinine phosphokinase increase (26%) and vomiting (10%).

Dr. Grisham also reported updated follow-up results through January 2019.

The median PFS in the updated analysis was 11.2 months with the MEK inhibitor and 14.1 months with chemotherapy, a difference that was not statistically significant (HR, 1.12; P = .752). Updated overall response rates were the same in both arms, at 24%.

A post hoc molecular analysis of 215 patients suggested a possible association between KRAS mutation and response to binimetinib.
 

Two MEKs, one ‘meh’

Discussant Jubilee Brown, MD, of the Levine Cancer Institute at Atrium Health in Charlotte, N.C., said that “with a 2% to 5% chance of response in patients with low-grade serous ovarian cancer, there is a low bar for any compound to demonstrate success.”

Regarding the MILO/ENGOT-ov11 trial, she noted that “this study did not meet its primary endpoint, but perhaps the endpoint is not reflective of the importance of the study.”

A different outcome might have occurred had investigators stratified patients by KRAS status upfront, comparing patients with KRAS mutations treated with binimetinib to KRAS wild-type patients treated with either a MEK inhibitor or physician’s choice of care, Dr. Brown said.

She agreed with the assertion by Dr. Gershenson and colleagues that improved PFS qualifies trametinib to be considered a new option for standard care, ”especially in a rare tumor setting with limited options. This is a huge win for patients.”

The trametinib study was sponsored by NRG Oncology and the UK National Cancer Research Institute. Dr. Gershenson disclosed relationships with NRG Oncology, Genentech, Novartis, Elsevier, and UpToDate, as well as stock in several companies.

The binimetinib study was sponsored by Pfizer. Dr. Grisham disclosed relationships with Clovis, Regeneron, Mateon, Amgen, Abbvie, OncLive, PRIME, MCM, and Medscape. MDedge News and Medscape are owned by the same parent organization.

Dr. Brown disclosed consulting for Biodesix, Caris, Clovis, Genentech, Invitae, Janssen, Olympus, OncLive, and Tempus.

SOURCE: Gershenson DM et al. SGO 2020, Abstract 42; Grisham RN et al. SGO 2020, Abstract 41.

The first installment of my new column was obsolete on arrival. It referred to walking abroad at midday, with no mention of masks and social distancing. The whole thing was so February 2020.

My last day in the office was in mid-March. Friday the 13th.

For a few weeks, I’ve been seeing patients remotely. I pitched telemedicine to an HMO about 30 years ago. I was hardly an innovator. Researchers had already shown the practical use of remote dermatology by then, using stored and forwarded images.

What I had in mind was visits by patients in nursing homes or too sick at home to come in. It always bothered me to see very aged and infirm patients brought to the office at great inconvenience and expense for what often turned out to be problems like xerosis or eczema that could have been managed quite well remotely.

The HMO never got back to me, though. There were too many hurdles, mostly bureaucratic rather than medical. Would insurance pay? What about consent? Malpractice? It has been interesting to watch the current crisis sweep away the inertia of such obstacles, including licensure considerations (seeing patients across state lines for cutaneous purposes). People get around to fixing the roof when it pours. Perhaps next time there will be tests, masks, respirators. Perhaps.

Seeing patients remotely has acquainted me with all the technical headaches everyone stuck at home talks and jokes about: Balky transmission (What did you say after, “and then the blood ...”?); patients who can’t figure out how to log on, or start the video, or unmute themselves, and on and on. Picture resolution is not great, as anyone knows from watching TV newscasters interview talking heads stuck in their homes.

I was never all that image-conscious, but my beard has grown fuller and my hair unkempter. Even though I sit at my desk, I do take care to keep my trousers on. Not taking any chances.

Everyone agonizes over what the “new normal” may be. Will people come back to doctors’ offices? Will practices survive economically if many patients don’t return to the office? Stay tuned. For a long time.

Mostly, though, remote visits seem to work. Helped if needed by additional, better-resolution emailed photos, it’s possible to make useful decisions, including which lesions can wait for in-person evaluation, until ...

... Until what? In an effort to keep this column up-to-the-nanosecond, I am writing it as many countries tentatively “open up.” Careful analysis of the knowledge behind this world-wide project shows ... not much. It seems to come down to some educated guesswork about what might work and what the risks might be, which leads to advice that differs widely from state to state and country to country. It’s as if people everywhere just decided that locking everyone down is a real drag, is financially ruinous, has a duration both uncertain and longer than most people and governments think they can handle, so let’s get out there and “be careful,” whatever that is said to mean.

And the risks? Well, more people will get sick and some will die. How many “extra” deaths are ethically acceptable? Thoughtful people are working on that. They’ll get back sometime to those who are still around.

I don’t blame anyone for our staggering ignorance about this terrifying new reality. But absorbing the ignorance in real time is not reassuring.

I have nothing but sympathy for those who are not emeritus, who have practices to sustain and families to feed. I didn’t ask to be born 73 years ago, and take no credit for having done so. So much of what happens to us depends on when and where we were born – two factors for which we deserve absolutely no credit – that it’s a wonder we take such pride in praising ourselves for what we think we accomplish. Having no better choice, we do the best we can.

Meantime, I am in a “high-risk” category. If I were obese, I could try to lose weight. But my risk factor is age, which tends not to decline. Risk-wise, there is just one way to exit my group.

So I don’t expect to get back to the office anytime soon. To paraphrase a comedian who shall remain nameless: I don’t want to live on in the hearts of men. I want to live on in my house.

Dr. Rockoff, who wrote the Dermatology News column “Under My Skin,” is now semiretired, after 40 years of practice in Brookline, Mass. He served on the clinical faculty at Tufts University, Boston, and taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available online. Write to him at dermnews@mdedge.com.

The first installment of my new column was obsolete on arrival. It referred to walking abroad at midday, with no mention of masks and social distancing. The whole thing was so February 2020.

My last day in the office was in mid-March. Friday the 13th.

For a few weeks, I’ve been seeing patients remotely. I pitched telemedicine to an HMO about 30 years ago. I was hardly an innovator. Researchers had already shown the practical use of remote dermatology by then, using stored and forwarded images.

What I had in mind was visits by patients in nursing homes or too sick at home to come in. It always bothered me to see very aged and infirm patients brought to the office at great inconvenience and expense for what often turned out to be problems like xerosis or eczema that could have been managed quite well remotely.

The HMO never got back to me, though. There were too many hurdles, mostly bureaucratic rather than medical. Would insurance pay? What about consent? Malpractice? It has been interesting to watch the current crisis sweep away the inertia of such obstacles, including licensure considerations (seeing patients across state lines for cutaneous purposes). People get around to fixing the roof when it pours. Perhaps next time there will be tests, masks, respirators. Perhaps.

Seeing patients remotely has acquainted me with all the technical headaches everyone stuck at home talks and jokes about: Balky transmission (What did you say after, “and then the blood ...”?); patients who can’t figure out how to log on, or start the video, or unmute themselves, and on and on. Picture resolution is not great, as anyone knows from watching TV newscasters interview talking heads stuck in their homes.

I was never all that image-conscious, but my beard has grown fuller and my hair unkempter. Even though I sit at my desk, I do take care to keep my trousers on. Not taking any chances.

Everyone agonizes over what the “new normal” may be. Will people come back to doctors’ offices? Will practices survive economically if many patients don’t return to the office? Stay tuned. For a long time.

Mostly, though, remote visits seem to work. Helped if needed by additional, better-resolution emailed photos, it’s possible to make useful decisions, including which lesions can wait for in-person evaluation, until ...

... Until what? In an effort to keep this column up-to-the-nanosecond, I am writing it as many countries tentatively “open up.” Careful analysis of the knowledge behind this world-wide project shows ... not much. It seems to come down to some educated guesswork about what might work and what the risks might be, which leads to advice that differs widely from state to state and country to country. It’s as if people everywhere just decided that locking everyone down is a real drag, is financially ruinous, has a duration both uncertain and longer than most people and governments think they can handle, so let’s get out there and “be careful,” whatever that is said to mean.

And the risks? Well, more people will get sick and some will die. How many “extra” deaths are ethically acceptable? Thoughtful people are working on that. They’ll get back sometime to those who are still around.

I don’t blame anyone for our staggering ignorance about this terrifying new reality. But absorbing the ignorance in real time is not reassuring.

I have nothing but sympathy for those who are not emeritus, who have practices to sustain and families to feed. I didn’t ask to be born 73 years ago, and take no credit for having done so. So much of what happens to us depends on when and where we were born – two factors for which we deserve absolutely no credit – that it’s a wonder we take such pride in praising ourselves for what we think we accomplish. Having no better choice, we do the best we can.

Meantime, I am in a “high-risk” category. If I were obese, I could try to lose weight. But my risk factor is age, which tends not to decline. Risk-wise, there is just one way to exit my group.

So I don’t expect to get back to the office anytime soon. To paraphrase a comedian who shall remain nameless: I don’t want to live on in the hearts of men. I want to live on in my house.

Dr. Rockoff, who wrote the Dermatology News column “Under My Skin,” is now semiretired, after 40 years of practice in Brookline, Mass. He served on the clinical faculty at Tufts University, Boston, and taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available online. Write to him at dermnews@mdedge.com.

The first installment of my new column was obsolete on arrival. It referred to walking abroad at midday, with no mention of masks and social distancing. The whole thing was so February 2020.

My last day in the office was in mid-March. Friday the 13th.

For a few weeks, I’ve been seeing patients remotely. I pitched telemedicine to an HMO about 30 years ago. I was hardly an innovator. Researchers had already shown the practical use of remote dermatology by then, using stored and forwarded images.

What I had in mind was visits by patients in nursing homes or too sick at home to come in. It always bothered me to see very aged and infirm patients brought to the office at great inconvenience and expense for what often turned out to be problems like xerosis or eczema that could have been managed quite well remotely.

The HMO never got back to me, though. There were too many hurdles, mostly bureaucratic rather than medical. Would insurance pay? What about consent? Malpractice? It has been interesting to watch the current crisis sweep away the inertia of such obstacles, including licensure considerations (seeing patients across state lines for cutaneous purposes). People get around to fixing the roof when it pours. Perhaps next time there will be tests, masks, respirators. Perhaps.

Seeing patients remotely has acquainted me with all the technical headaches everyone stuck at home talks and jokes about: Balky transmission (What did you say after, “and then the blood ...”?); patients who can’t figure out how to log on, or start the video, or unmute themselves, and on and on. Picture resolution is not great, as anyone knows from watching TV newscasters interview talking heads stuck in their homes.

I was never all that image-conscious, but my beard has grown fuller and my hair unkempter. Even though I sit at my desk, I do take care to keep my trousers on. Not taking any chances.

Everyone agonizes over what the “new normal” may be. Will people come back to doctors’ offices? Will practices survive economically if many patients don’t return to the office? Stay tuned. For a long time.

Mostly, though, remote visits seem to work. Helped if needed by additional, better-resolution emailed photos, it’s possible to make useful decisions, including which lesions can wait for in-person evaluation, until ...

... Until what? In an effort to keep this column up-to-the-nanosecond, I am writing it as many countries tentatively “open up.” Careful analysis of the knowledge behind this world-wide project shows ... not much. It seems to come down to some educated guesswork about what might work and what the risks might be, which leads to advice that differs widely from state to state and country to country. It’s as if people everywhere just decided that locking everyone down is a real drag, is financially ruinous, has a duration both uncertain and longer than most people and governments think they can handle, so let’s get out there and “be careful,” whatever that is said to mean.

And the risks? Well, more people will get sick and some will die. How many “extra” deaths are ethically acceptable? Thoughtful people are working on that. They’ll get back sometime to those who are still around.

I don’t blame anyone for our staggering ignorance about this terrifying new reality. But absorbing the ignorance in real time is not reassuring.

I have nothing but sympathy for those who are not emeritus, who have practices to sustain and families to feed. I didn’t ask to be born 73 years ago, and take no credit for having done so. So much of what happens to us depends on when and where we were born – two factors for which we deserve absolutely no credit – that it’s a wonder we take such pride in praising ourselves for what we think we accomplish. Having no better choice, we do the best we can.

Meantime, I am in a “high-risk” category. If I were obese, I could try to lose weight. But my risk factor is age, which tends not to decline. Risk-wise, there is just one way to exit my group.

So I don’t expect to get back to the office anytime soon. To paraphrase a comedian who shall remain nameless: I don’t want to live on in the hearts of men. I want to live on in my house.

Dr. Rockoff, who wrote the Dermatology News column “Under My Skin,” is now semiretired, after 40 years of practice in Brookline, Mass. He served on the clinical faculty at Tufts University, Boston, and taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available online. Write to him at dermnews@mdedge.com.

The younger an ICU patient with severe COVID-19 is, the more obese that patient tends to be, according to a new analysis published in The Lancet.

“By itself, obesity seems to be a sufficient risk factor to start seeing younger people landing in the ICU,” said the study’s lead author, David Kass, MD, a professor of cardiology and medicine at Johns Hopkins University School of Medicine in Baltimore, Maryland.

“In that sense, there’s a simple message: If you’re very, very overweight, don’t think that if you’re 35 you’re that much safer [from severe COVID-19] than your mother or grandparents or others in their 60s or 70s,” Kass told Medscape Medical News.

The findings, which Kass describes as a “2-week snapshot” of 265 patients (58% male) in late March and early April at a handful of university hospitals in the United States reinforces other recent research indicating that obesity is one of the biggest risk factors for severe COVID-19 disease, particularly among younger patients. In addition, a large British study showed that, after adjusting for comorbidities, obesity was a significant factor associated with in-hospital death in COVID-19.

But this new analysis stands out as the only dataset to date that specifically “asks the question relative to age” of whether severe COVID-19 disease correlates to ICU treatment, he said.

The mean age of his study population of ICU patients was 55, Kass said, “and that was young, not what we were expecting.”

“Even with the first 20 patients, we were already seeing younger people and they definitely were heavier, with plenty of patients with a BMI over 35 kg/m²,” he added. “The relationship was pretty tight, pretty quick.”

“Just don’t make the assumption that any of us are too young to be vulnerable if, in fact, this is an aspect of our bodies,” he said.

Steven Heymsfield, MD, past president and a spokesperson for the Obesity Society, agrees with Kass’ conclusions.

“One thing we’ve had on our minds is that the prototype of a person with this disease is older...but now if we get [a patient] who’s symptomatic and 40 and obese, we shouldn’t assume they have some other disease,” Heymsfield told Medscape Medical News.

“We should think of them as a susceptible population.”

Kass and colleagues agree. “Public messaging to younger adults, reducing the threshold for virus testing in obese individuals, and maintaining greater vigilance for this at-risk population should reduce the prevalence of severe COVID-19 disease [among those with obesity],” they state.

“I think it’s a mental adjustment from a health care standpoint, which might hopefully help target the folks who are at higher risk before they get into trouble,” Kass told Medscape Medical News.
 

Trio of mechanisms explain obesity’s extra COVID-19 risks

Kass and coauthors write that, in analyzing their data, they anticipated similar results to the largest study of 1591 ICU patients from Italy in which only 203 were younger than 51 years. Common comorbidities among those patients included hypertension, cardiovascular disease, and type 2 diabetes, with similar data reported from China.

When the COVID-19 epidemic accelerated in the United States, older age was also identified as a risk factor. Obesity had not yet been added to this list, Kass noted. But following informal discussions with colleagues in other ICUs around the country, he decided to investigate further as to whether it was an underappreciated risk factor.

Kass and colleagues did a quick evaluation of the link between BMI and age of patients with COVID-19 admitted to ICUs at Johns Hopkins, University of Cincinnati, New York University, University of Washington, Florida Health, and University of Pennsylvania.

The “significant inverse correlation between age and BMI” showed younger ICU patients were more likely to be obese, with no difference by gender.

Median BMI among study participants was 29.3 kg/m², with only a quarter having a BMI lower than 26 kg/m² and another 25% having a BMI higher than 34.7 kg/m².

Kass acknowledged that it wasn’t possible with this simple dataset to account for any other potential confounders, but he told Medscape Medical News that, “while diabetes, cardiovascular disease, and hypertension, for example, can occur with obesity, this is generally less so in younger populations as it takes time for the other comorbidities to develop.”

He said several mechanisms could explain why obesity predisposes patients with COVID-19 to severe disease.

For one, obesity places extra pressure on the diaphragm while lying on the back, restricting breathing.

“Morbid obesity itself is sort of proinflammatory,” he continued.

“Here we’ve got a viral infection where the early reports suggest that cytokine storms and immune mishandling of the virus are why it’s so much more severe than other forms of coronavirus we’ve seen before. So if you have someone with an already underlying proinflammatory state, this could be a reason there’s higher risk.”

Additionally, the angiotensin-converting enzyme-2 (ACE-2) receptor to which the SARS-CoV-2 virus that causes COVID-19 attaches is expressed in higher amounts in adipose tissue than the lungs, Kass noted.

“This could turn into kind of a viral replication depot,” he explained. “You may well be brewing more virus as a component of obesity.”
 

Sensitivity needed in public messaging about risks, but test sooner

With an obesity rate of about 40% in the United States, the results are particularly relevant for Americans, Kass and Heymsfield say, noting that the country’s “obesity belt” runs through the South.

Heymsfield, who wasn’t part of the new analysis, notes that public messaging around severe COVID-19 risks to younger adults with obesity is “tricky,” especially because the virus is “still pretty common in nonobese people.”

Kass agrees, noting, “it’s difficult to turn to 40% of the population and say: ‘You guys have to watch it.’ ”

But the mounting research findings necessitate linking obesity with severe COVID-19 disease and perhaps testing patients in this category for the virus sooner before symptoms become severe.

And of note, since shortness of breath is common among people with obesity regardless of illness, similar COVID-19 symptoms might catch these individuals unaware, pointed out Heymsfield, who is also a professor in the Metabolism and Body Composition Lab at Pennington Biomedical Research Center at Louisiana State University, Baton Rouge.

“They may find themselves literally unable to breathe, and the concern would be that they wait much too long to come in” for treatment, he said. Typically, people can deteriorate between day 7 and 10 of the COVID-19 infection.

Individuals with obesity “need to be educated to recognize the serious complications of COVID-19 often appear suddenly, although the virus has sometimes been working its way through the body for a long time,” he concluded.

Kass and Heymsfield have declared no relevant financial relationships.

This article first appeared on Medscape.com.

The younger an ICU patient with severe COVID-19 is, the more obese that patient tends to be, according to a new analysis published in The Lancet.

“By itself, obesity seems to be a sufficient risk factor to start seeing younger people landing in the ICU,” said the study’s lead author, David Kass, MD, a professor of cardiology and medicine at Johns Hopkins University School of Medicine in Baltimore, Maryland.

“In that sense, there’s a simple message: If you’re very, very overweight, don’t think that if you’re 35 you’re that much safer [from severe COVID-19] than your mother or grandparents or others in their 60s or 70s,” Kass told Medscape Medical News.

The findings, which Kass describes as a “2-week snapshot” of 265 patients (58% male) in late March and early April at a handful of university hospitals in the United States reinforces other recent research indicating that obesity is one of the biggest risk factors for severe COVID-19 disease, particularly among younger patients. In addition, a large British study showed that, after adjusting for comorbidities, obesity was a significant factor associated with in-hospital death in COVID-19.

But this new analysis stands out as the only dataset to date that specifically “asks the question relative to age” of whether severe COVID-19 disease correlates to ICU treatment, he said.

The mean age of his study population of ICU patients was 55, Kass said, “and that was young, not what we were expecting.”

“Even with the first 20 patients, we were already seeing younger people and they definitely were heavier, with plenty of patients with a BMI over 35 kg/m²,” he added. “The relationship was pretty tight, pretty quick.”

“Just don’t make the assumption that any of us are too young to be vulnerable if, in fact, this is an aspect of our bodies,” he said.

Steven Heymsfield, MD, past president and a spokesperson for the Obesity Society, agrees with Kass’ conclusions.

“One thing we’ve had on our minds is that the prototype of a person with this disease is older...but now if we get [a patient] who’s symptomatic and 40 and obese, we shouldn’t assume they have some other disease,” Heymsfield told Medscape Medical News.

“We should think of them as a susceptible population.”

Kass and colleagues agree. “Public messaging to younger adults, reducing the threshold for virus testing in obese individuals, and maintaining greater vigilance for this at-risk population should reduce the prevalence of severe COVID-19 disease [among those with obesity],” they state.

“I think it’s a mental adjustment from a health care standpoint, which might hopefully help target the folks who are at higher risk before they get into trouble,” Kass told Medscape Medical News.
 

Trio of mechanisms explain obesity’s extra COVID-19 risks

Kass and coauthors write that, in analyzing their data, they anticipated similar results to the largest study of 1591 ICU patients from Italy in which only 203 were younger than 51 years. Common comorbidities among those patients included hypertension, cardiovascular disease, and type 2 diabetes, with similar data reported from China.

When the COVID-19 epidemic accelerated in the United States, older age was also identified as a risk factor. Obesity had not yet been added to this list, Kass noted. But following informal discussions with colleagues in other ICUs around the country, he decided to investigate further as to whether it was an underappreciated risk factor.

Kass and colleagues did a quick evaluation of the link between BMI and age of patients with COVID-19 admitted to ICUs at Johns Hopkins, University of Cincinnati, New York University, University of Washington, Florida Health, and University of Pennsylvania.

The “significant inverse correlation between age and BMI” showed younger ICU patients were more likely to be obese, with no difference by gender.

Median BMI among study participants was 29.3 kg/m², with only a quarter having a BMI lower than 26 kg/m² and another 25% having a BMI higher than 34.7 kg/m².

Kass acknowledged that it wasn’t possible with this simple dataset to account for any other potential confounders, but he told Medscape Medical News that, “while diabetes, cardiovascular disease, and hypertension, for example, can occur with obesity, this is generally less so in younger populations as it takes time for the other comorbidities to develop.”

He said several mechanisms could explain why obesity predisposes patients with COVID-19 to severe disease.

For one, obesity places extra pressure on the diaphragm while lying on the back, restricting breathing.

“Morbid obesity itself is sort of proinflammatory,” he continued.

“Here we’ve got a viral infection where the early reports suggest that cytokine storms and immune mishandling of the virus are why it’s so much more severe than other forms of coronavirus we’ve seen before. So if you have someone with an already underlying proinflammatory state, this could be a reason there’s higher risk.”

Additionally, the angiotensin-converting enzyme-2 (ACE-2) receptor to which the SARS-CoV-2 virus that causes COVID-19 attaches is expressed in higher amounts in adipose tissue than the lungs, Kass noted.

“This could turn into kind of a viral replication depot,” he explained. “You may well be brewing more virus as a component of obesity.”
 

Sensitivity needed in public messaging about risks, but test sooner

With an obesity rate of about 40% in the United States, the results are particularly relevant for Americans, Kass and Heymsfield say, noting that the country’s “obesity belt” runs through the South.

Heymsfield, who wasn’t part of the new analysis, notes that public messaging around severe COVID-19 risks to younger adults with obesity is “tricky,” especially because the virus is “still pretty common in nonobese people.”

Kass agrees, noting, “it’s difficult to turn to 40% of the population and say: ‘You guys have to watch it.’ ”

But the mounting research findings necessitate linking obesity with severe COVID-19 disease and perhaps testing patients in this category for the virus sooner before symptoms become severe.

And of note, since shortness of breath is common among people with obesity regardless of illness, similar COVID-19 symptoms might catch these individuals unaware, pointed out Heymsfield, who is also a professor in the Metabolism and Body Composition Lab at Pennington Biomedical Research Center at Louisiana State University, Baton Rouge.

“They may find themselves literally unable to breathe, and the concern would be that they wait much too long to come in” for treatment, he said. Typically, people can deteriorate between day 7 and 10 of the COVID-19 infection.

Individuals with obesity “need to be educated to recognize the serious complications of COVID-19 often appear suddenly, although the virus has sometimes been working its way through the body for a long time,” he concluded.

Kass and Heymsfield have declared no relevant financial relationships.

This article first appeared on Medscape.com.

The younger an ICU patient with severe COVID-19 is, the more obese that patient tends to be, according to a new analysis published in The Lancet.

“By itself, obesity seems to be a sufficient risk factor to start seeing younger people landing in the ICU,” said the study’s lead author, David Kass, MD, a professor of cardiology and medicine at Johns Hopkins University School of Medicine in Baltimore, Maryland.

“In that sense, there’s a simple message: If you’re very, very overweight, don’t think that if you’re 35 you’re that much safer [from severe COVID-19] than your mother or grandparents or others in their 60s or 70s,” Kass told Medscape Medical News.

The findings, which Kass describes as a “2-week snapshot” of 265 patients (58% male) in late March and early April at a handful of university hospitals in the United States reinforces other recent research indicating that obesity is one of the biggest risk factors for severe COVID-19 disease, particularly among younger patients. In addition, a large British study showed that, after adjusting for comorbidities, obesity was a significant factor associated with in-hospital death in COVID-19.

But this new analysis stands out as the only dataset to date that specifically “asks the question relative to age” of whether severe COVID-19 disease correlates to ICU treatment, he said.

The mean age of his study population of ICU patients was 55, Kass said, “and that was young, not what we were expecting.”

“Even with the first 20 patients, we were already seeing younger people and they definitely were heavier, with plenty of patients with a BMI over 35 kg/m²,” he added. “The relationship was pretty tight, pretty quick.”

“Just don’t make the assumption that any of us are too young to be vulnerable if, in fact, this is an aspect of our bodies,” he said.

Steven Heymsfield, MD, past president and a spokesperson for the Obesity Society, agrees with Kass’ conclusions.

“One thing we’ve had on our minds is that the prototype of a person with this disease is older...but now if we get [a patient] who’s symptomatic and 40 and obese, we shouldn’t assume they have some other disease,” Heymsfield told Medscape Medical News.

“We should think of them as a susceptible population.”

Kass and colleagues agree. “Public messaging to younger adults, reducing the threshold for virus testing in obese individuals, and maintaining greater vigilance for this at-risk population should reduce the prevalence of severe COVID-19 disease [among those with obesity],” they state.

“I think it’s a mental adjustment from a health care standpoint, which might hopefully help target the folks who are at higher risk before they get into trouble,” Kass told Medscape Medical News.
 

Trio of mechanisms explain obesity’s extra COVID-19 risks

Kass and coauthors write that, in analyzing their data, they anticipated similar results to the largest study of 1591 ICU patients from Italy in which only 203 were younger than 51 years. Common comorbidities among those patients included hypertension, cardiovascular disease, and type 2 diabetes, with similar data reported from China.

When the COVID-19 epidemic accelerated in the United States, older age was also identified as a risk factor. Obesity had not yet been added to this list, Kass noted. But following informal discussions with colleagues in other ICUs around the country, he decided to investigate further as to whether it was an underappreciated risk factor.

Kass and colleagues did a quick evaluation of the link between BMI and age of patients with COVID-19 admitted to ICUs at Johns Hopkins, University of Cincinnati, New York University, University of Washington, Florida Health, and University of Pennsylvania.

The “significant inverse correlation between age and BMI” showed younger ICU patients were more likely to be obese, with no difference by gender.

Median BMI among study participants was 29.3 kg/m², with only a quarter having a BMI lower than 26 kg/m² and another 25% having a BMI higher than 34.7 kg/m².

Kass acknowledged that it wasn’t possible with this simple dataset to account for any other potential confounders, but he told Medscape Medical News that, “while diabetes, cardiovascular disease, and hypertension, for example, can occur with obesity, this is generally less so in younger populations as it takes time for the other comorbidities to develop.”

He said several mechanisms could explain why obesity predisposes patients with COVID-19 to severe disease.

For one, obesity places extra pressure on the diaphragm while lying on the back, restricting breathing.

“Morbid obesity itself is sort of proinflammatory,” he continued.

“Here we’ve got a viral infection where the early reports suggest that cytokine storms and immune mishandling of the virus are why it’s so much more severe than other forms of coronavirus we’ve seen before. So if you have someone with an already underlying proinflammatory state, this could be a reason there’s higher risk.”

Additionally, the angiotensin-converting enzyme-2 (ACE-2) receptor to which the SARS-CoV-2 virus that causes COVID-19 attaches is expressed in higher amounts in adipose tissue than the lungs, Kass noted.

“This could turn into kind of a viral replication depot,” he explained. “You may well be brewing more virus as a component of obesity.”
 

Sensitivity needed in public messaging about risks, but test sooner

With an obesity rate of about 40% in the United States, the results are particularly relevant for Americans, Kass and Heymsfield say, noting that the country’s “obesity belt” runs through the South.

Heymsfield, who wasn’t part of the new analysis, notes that public messaging around severe COVID-19 risks to younger adults with obesity is “tricky,” especially because the virus is “still pretty common in nonobese people.”

Kass agrees, noting, “it’s difficult to turn to 40% of the population and say: ‘You guys have to watch it.’ ”

But the mounting research findings necessitate linking obesity with severe COVID-19 disease and perhaps testing patients in this category for the virus sooner before symptoms become severe.

And of note, since shortness of breath is common among people with obesity regardless of illness, similar COVID-19 symptoms might catch these individuals unaware, pointed out Heymsfield, who is also a professor in the Metabolism and Body Composition Lab at Pennington Biomedical Research Center at Louisiana State University, Baton Rouge.

“They may find themselves literally unable to breathe, and the concern would be that they wait much too long to come in” for treatment, he said. Typically, people can deteriorate between day 7 and 10 of the COVID-19 infection.

Individuals with obesity “need to be educated to recognize the serious complications of COVID-19 often appear suddenly, although the virus has sometimes been working its way through the body for a long time,” he concluded.

Kass and Heymsfield have declared no relevant financial relationships.

This article first appeared on Medscape.com.

A 27-year-old man presented to the urgent care clinic with acute bilateral hand swelling, blisters, numbness, and pain. History taking revealed that these symptoms developed after he was locked outside of his apartment for 45 minutes in –22°C (–8°F) weather following a night of heavy drinking.

On physical examination, the patient had a temperature of 36.2°C (97.2°F) and a heart rate of 116 beats/min. He had edema, tenderness, decreased sensation, and distal cyanosis involving all of his fingers (FIGURE 1). He also had large, tense, clear bullae over the dorsal aspect of his fingers (FIGURE 2).

IMAGE COURTESY OF MORTEZA KHODAEE, MD, MPH

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Frostbite is the result of tissue freezing, which generally occurs after prolonged exposure to freezing temperatures (typically –4°C or below).^1,2 The majority (~90%) of frostbite injuries occur in the hands and feet; however, frostbite has also been observed in the face, perineum, buttocks, and male genitalia.³

Angiography should be performed on patients with third- or fourth-degree frostbite. In cases of vascular occlusion, tPA and heparin can be started to reduce the risk for amputation.

Frostbite is a clinical diagnosis based on a history of sustained exposure to freezing temperatures, paresthesia of affected areas, and typical skin changes. Evidence is lacking regarding the epidemiology of frostbite within the general population.²

Pathophysiology. Intra- and extracellular ice crystal formation causes fluid and electrolyte disturbances, cell dehydration, lipid denaturation, and subsequent cell death.¹ After thawing, progressive tissue ischemia can occur as a result of endothelial damage and dysfunction, intravascular sludging, increased inflammatory markers, an influx of free radicals, and microvascular thrombosis.¹

Classification. Traditionally, frostbite has been classified according to a 4-tiered system based on tissue appearance after rewarming.² First-degree frostbite is characterized by white plaques with surrounding erythema; second degree by edema and clear or cloudy vesicles; third degree by hemorrhagic bullae; and fourth degree by cold and hard tissue that eventually progresses to gangrene.²

A simpler scheme designates frostbite as either superficial (corresponding to first- or second-degree frostbite) or deep (corresponding to third- or fourth-degree frostbite) with presumed muscle and bone involvement.²

Continue to: Risk factors

Risk factors. Frostbite is often associated with risk factors such as alcohol or drug intoxication, vehicular failure or trauma, immobilizing trauma, psychiatric illness, homelessness, Raynaud phenomenon, peripheral vascular disease, diabetes, inadequate clothing, previous cold-weather injury, outdoor winter recreation, and the use of certain medications (eg, beta-blockers).^1-3 Apart from environmental exposure, frostbite can also occur by direct contact with freezing materials, such as ice packs or industrial refrigerants.³

Differential includes nonfreezing injuries

Frostnip, pernio, and trench foot are other cold-weather injuries distinguished by the absence of tissue freezing.⁴ Raynaud phenomenon is a condition that is triggered by either cold temperatures or emotional stress.⁵

Frostnip is characterized by pallor and paresthesia of exposed areas. It may precede frostbite, but it quickly resolves after rewarming.²

Pernio occurs when skin is exposed to damp, cold, nonfreezing environments.⁶ It results in edematous and inflammatory skin lesions that may be painful, pruritic, violaceous, or erythematous.⁶ These lesions are typically found over the fingers, toes, nose, ears, buttocks, or thighs.^4,6 Pernio may be classified as either primary or secondary disease.⁵ Primary pernio is considered idiopathic.⁶ Secondary pernio is thought to be either drug induced or due to underlying autoimmune diseases, such as hepatitis or cryopathy.⁶

Trench foot develops under similar conditions to pernio but requires exposure to a wet environment for at least 10 to 14 hours.⁷ It is characterized by foot pain, paresthesia, pruritus, edema, erythema, cyanosis, blisters, and even gangrene if left untreated.⁷

Continue to: Raynaud phenomenon

Raynaud phenomenon results from transient, acral vasocontraction and manifests as well-demarcated pallor, cyanosis, and then erythema as the affected body part reperfuses.⁵ Similar to pernio, it can be categorized as either primary or secondary.⁵ Primary phenomenon is idiopathic. Secondary phenomenon is thought to be a result of autoimmune disease, use of certain medications, occupational vibratory exposure, obstructive vascular disease, or infection.⁵

In the absence of a history of exposure to subfreezing temperatures, frostbite can be excluded from the differential diagnosis.

Treatment entails rewarming

The aim of frostbite treatment is to save injured cells and minimize tissue loss.¹ This is accomplished through rapid rewarming and—in severe cases—reperfusion techniques.

Tissue should be rewarmed in a 37°C to 39°C water bath with povidone iodine or chlorhexidine added for antiseptic effect.¹ All efforts should be made to avoid refreezing or trauma, as this could worsen the initial injury.² Oral or intravenous hydration may be offered to optimize fluid status.¹ Supplemental oxygen may be administered to maintain saturations above 90%.¹ Nonsteroidal anti-inflammatory drugs are helpful for analgesia and anti-­inflammatory effect, and opioids can be used for breakthrough pain.¹ It is recommended that blisters be drained in a sterile fashion and that all affected tissue be covered with topical aloe vera and a loose dressing.^1,2,4

Treatment of severe frostbite. Angiography should be performed on all patients with third- or fourth-degree frostbite.³ If imaging shows evidence of vascular occlusion, tissue plasminogen activator (tPA) and heparin can be initiated within 24 hours to reduce the risk for amputation.^8-10

Continue to: Iloprost is another...

Iloprost is another proposed treatment for severe frostbite. It is a prostacyclin analog that may lower the amputation rate in patients with at least third-degree frostbite.¹¹ Unlike tPA, iloprost may be given to trauma patients, and it can be used more than 24 hours after injury.²

In cases of fourth-degree frostbite that is not successfully reperfused, amputation is delayed until dry gangrene develops. This often takes weeks to months.¹²

Our patient underwent rewarming and was orally rehydrated. He was discharged home with ibuprofen, oxycodone-­acetaminophen, topical aloe vera, and loose dressings. His bullae enlarged the next day (FIGURE 3). One week later, his blisters were debrided and dressed with silver sulfadiazine at his plastic surgery follow-up. He experienced sensory deficits for a few months, but eventually made a full recovery after 6 months with no remaining sequelae.

IMAGE COURTESY OF MORTEZA KHODAEE, MD, MPH

ACKNOWLEDGEMENT
The authors thank Lisa Kim, MD, for her clinical care of this patient.

CORRESPONDENCE
Morteza Khodaee, MD, MPH, University of Colorado School of Medicine, Department of Family Medicine, AFW Clinic, 3055 Roslyn Street, Denver, CO 80238; morteza.khodaee@ cuanschutz.edu

A 27-year-old man presented to the urgent care clinic with acute bilateral hand swelling, blisters, numbness, and pain. History taking revealed that these symptoms developed after he was locked outside of his apartment for 45 minutes in –22°C (–8°F) weather following a night of heavy drinking.

On physical examination, the patient had a temperature of 36.2°C (97.2°F) and a heart rate of 116 beats/min. He had edema, tenderness, decreased sensation, and distal cyanosis involving all of his fingers (FIGURE 1). He also had large, tense, clear bullae over the dorsal aspect of his fingers (FIGURE 2).

IMAGE COURTESY OF MORTEZA KHODAEE, MD, MPH

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Frostbite is the result of tissue freezing, which generally occurs after prolonged exposure to freezing temperatures (typically –4°C or below).^1,2 The majority (~90%) of frostbite injuries occur in the hands and feet; however, frostbite has also been observed in the face, perineum, buttocks, and male genitalia.³

Angiography should be performed on patients with third- or fourth-degree frostbite. In cases of vascular occlusion, tPA and heparin can be started to reduce the risk for amputation.

Frostbite is a clinical diagnosis based on a history of sustained exposure to freezing temperatures, paresthesia of affected areas, and typical skin changes. Evidence is lacking regarding the epidemiology of frostbite within the general population.²

Pathophysiology. Intra- and extracellular ice crystal formation causes fluid and electrolyte disturbances, cell dehydration, lipid denaturation, and subsequent cell death.¹ After thawing, progressive tissue ischemia can occur as a result of endothelial damage and dysfunction, intravascular sludging, increased inflammatory markers, an influx of free radicals, and microvascular thrombosis.¹

Classification. Traditionally, frostbite has been classified according to a 4-tiered system based on tissue appearance after rewarming.² First-degree frostbite is characterized by white plaques with surrounding erythema; second degree by edema and clear or cloudy vesicles; third degree by hemorrhagic bullae; and fourth degree by cold and hard tissue that eventually progresses to gangrene.²

A simpler scheme designates frostbite as either superficial (corresponding to first- or second-degree frostbite) or deep (corresponding to third- or fourth-degree frostbite) with presumed muscle and bone involvement.²

Continue to: Risk factors

Risk factors. Frostbite is often associated with risk factors such as alcohol or drug intoxication, vehicular failure or trauma, immobilizing trauma, psychiatric illness, homelessness, Raynaud phenomenon, peripheral vascular disease, diabetes, inadequate clothing, previous cold-weather injury, outdoor winter recreation, and the use of certain medications (eg, beta-blockers).^1-3 Apart from environmental exposure, frostbite can also occur by direct contact with freezing materials, such as ice packs or industrial refrigerants.³

Differential includes nonfreezing injuries

Frostnip, pernio, and trench foot are other cold-weather injuries distinguished by the absence of tissue freezing.⁴ Raynaud phenomenon is a condition that is triggered by either cold temperatures or emotional stress.⁵

Frostnip is characterized by pallor and paresthesia of exposed areas. It may precede frostbite, but it quickly resolves after rewarming.²

Pernio occurs when skin is exposed to damp, cold, nonfreezing environments.⁶ It results in edematous and inflammatory skin lesions that may be painful, pruritic, violaceous, or erythematous.⁶ These lesions are typically found over the fingers, toes, nose, ears, buttocks, or thighs.^4,6 Pernio may be classified as either primary or secondary disease.⁵ Primary pernio is considered idiopathic.⁶ Secondary pernio is thought to be either drug induced or due to underlying autoimmune diseases, such as hepatitis or cryopathy.⁶

Trench foot develops under similar conditions to pernio but requires exposure to a wet environment for at least 10 to 14 hours.⁷ It is characterized by foot pain, paresthesia, pruritus, edema, erythema, cyanosis, blisters, and even gangrene if left untreated.⁷

Continue to: Raynaud phenomenon

Raynaud phenomenon results from transient, acral vasocontraction and manifests as well-demarcated pallor, cyanosis, and then erythema as the affected body part reperfuses.⁵ Similar to pernio, it can be categorized as either primary or secondary.⁵ Primary phenomenon is idiopathic. Secondary phenomenon is thought to be a result of autoimmune disease, use of certain medications, occupational vibratory exposure, obstructive vascular disease, or infection.⁵

In the absence of a history of exposure to subfreezing temperatures, frostbite can be excluded from the differential diagnosis.

Treatment entails rewarming

The aim of frostbite treatment is to save injured cells and minimize tissue loss.¹ This is accomplished through rapid rewarming and—in severe cases—reperfusion techniques.

Tissue should be rewarmed in a 37°C to 39°C water bath with povidone iodine or chlorhexidine added for antiseptic effect.¹ All efforts should be made to avoid refreezing or trauma, as this could worsen the initial injury.² Oral or intravenous hydration may be offered to optimize fluid status.¹ Supplemental oxygen may be administered to maintain saturations above 90%.¹ Nonsteroidal anti-inflammatory drugs are helpful for analgesia and anti-­inflammatory effect, and opioids can be used for breakthrough pain.¹ It is recommended that blisters be drained in a sterile fashion and that all affected tissue be covered with topical aloe vera and a loose dressing.^1,2,4

Treatment of severe frostbite. Angiography should be performed on all patients with third- or fourth-degree frostbite.³ If imaging shows evidence of vascular occlusion, tissue plasminogen activator (tPA) and heparin can be initiated within 24 hours to reduce the risk for amputation.^8-10

Continue to: Iloprost is another...

Iloprost is another proposed treatment for severe frostbite. It is a prostacyclin analog that may lower the amputation rate in patients with at least third-degree frostbite.¹¹ Unlike tPA, iloprost may be given to trauma patients, and it can be used more than 24 hours after injury.²

In cases of fourth-degree frostbite that is not successfully reperfused, amputation is delayed until dry gangrene develops. This often takes weeks to months.¹²

Our patient underwent rewarming and was orally rehydrated. He was discharged home with ibuprofen, oxycodone-­acetaminophen, topical aloe vera, and loose dressings. His bullae enlarged the next day (FIGURE 3). One week later, his blisters were debrided and dressed with silver sulfadiazine at his plastic surgery follow-up. He experienced sensory deficits for a few months, but eventually made a full recovery after 6 months with no remaining sequelae.

IMAGE COURTESY OF MORTEZA KHODAEE, MD, MPH

ACKNOWLEDGEMENT
The authors thank Lisa Kim, MD, for her clinical care of this patient.

CORRESPONDENCE
Morteza Khodaee, MD, MPH, University of Colorado School of Medicine, Department of Family Medicine, AFW Clinic, 3055 Roslyn Street, Denver, CO 80238; morteza.khodaee@ cuanschutz.edu

A 27-year-old man presented to the urgent care clinic with acute bilateral hand swelling, blisters, numbness, and pain. History taking revealed that these symptoms developed after he was locked outside of his apartment for 45 minutes in –22°C (–8°F) weather following a night of heavy drinking.

On physical examination, the patient had a temperature of 36.2°C (97.2°F) and a heart rate of 116 beats/min. He had edema, tenderness, decreased sensation, and distal cyanosis involving all of his fingers (FIGURE 1). He also had large, tense, clear bullae over the dorsal aspect of his fingers (FIGURE 2).

IMAGE COURTESY OF MORTEZA KHODAEE, MD, MPH

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Frostbite is the result of tissue freezing, which generally occurs after prolonged exposure to freezing temperatures (typically –4°C or below).^1,2 The majority (~90%) of frostbite injuries occur in the hands and feet; however, frostbite has also been observed in the face, perineum, buttocks, and male genitalia.³

Angiography should be performed on patients with third- or fourth-degree frostbite. In cases of vascular occlusion, tPA and heparin can be started to reduce the risk for amputation.

Frostbite is a clinical diagnosis based on a history of sustained exposure to freezing temperatures, paresthesia of affected areas, and typical skin changes. Evidence is lacking regarding the epidemiology of frostbite within the general population.²

Pathophysiology. Intra- and extracellular ice crystal formation causes fluid and electrolyte disturbances, cell dehydration, lipid denaturation, and subsequent cell death.¹ After thawing, progressive tissue ischemia can occur as a result of endothelial damage and dysfunction, intravascular sludging, increased inflammatory markers, an influx of free radicals, and microvascular thrombosis.¹

Classification. Traditionally, frostbite has been classified according to a 4-tiered system based on tissue appearance after rewarming.² First-degree frostbite is characterized by white plaques with surrounding erythema; second degree by edema and clear or cloudy vesicles; third degree by hemorrhagic bullae; and fourth degree by cold and hard tissue that eventually progresses to gangrene.²

A simpler scheme designates frostbite as either superficial (corresponding to first- or second-degree frostbite) or deep (corresponding to third- or fourth-degree frostbite) with presumed muscle and bone involvement.²

Continue to: Risk factors

Risk factors. Frostbite is often associated with risk factors such as alcohol or drug intoxication, vehicular failure or trauma, immobilizing trauma, psychiatric illness, homelessness, Raynaud phenomenon, peripheral vascular disease, diabetes, inadequate clothing, previous cold-weather injury, outdoor winter recreation, and the use of certain medications (eg, beta-blockers).^1-3 Apart from environmental exposure, frostbite can also occur by direct contact with freezing materials, such as ice packs or industrial refrigerants.³

Differential includes nonfreezing injuries

Frostnip, pernio, and trench foot are other cold-weather injuries distinguished by the absence of tissue freezing.⁴ Raynaud phenomenon is a condition that is triggered by either cold temperatures or emotional stress.⁵

Frostnip is characterized by pallor and paresthesia of exposed areas. It may precede frostbite, but it quickly resolves after rewarming.²

Pernio occurs when skin is exposed to damp, cold, nonfreezing environments.⁶ It results in edematous and inflammatory skin lesions that may be painful, pruritic, violaceous, or erythematous.⁶ These lesions are typically found over the fingers, toes, nose, ears, buttocks, or thighs.^4,6 Pernio may be classified as either primary or secondary disease.⁵ Primary pernio is considered idiopathic.⁶ Secondary pernio is thought to be either drug induced or due to underlying autoimmune diseases, such as hepatitis or cryopathy.⁶

Trench foot develops under similar conditions to pernio but requires exposure to a wet environment for at least 10 to 14 hours.⁷ It is characterized by foot pain, paresthesia, pruritus, edema, erythema, cyanosis, blisters, and even gangrene if left untreated.⁷

Continue to: Raynaud phenomenon

Raynaud phenomenon results from transient, acral vasocontraction and manifests as well-demarcated pallor, cyanosis, and then erythema as the affected body part reperfuses.⁵ Similar to pernio, it can be categorized as either primary or secondary.⁵ Primary phenomenon is idiopathic. Secondary phenomenon is thought to be a result of autoimmune disease, use of certain medications, occupational vibratory exposure, obstructive vascular disease, or infection.⁵

In the absence of a history of exposure to subfreezing temperatures, frostbite can be excluded from the differential diagnosis.

Treatment entails rewarming

The aim of frostbite treatment is to save injured cells and minimize tissue loss.¹ This is accomplished through rapid rewarming and—in severe cases—reperfusion techniques.

Tissue should be rewarmed in a 37°C to 39°C water bath with povidone iodine or chlorhexidine added for antiseptic effect.¹ All efforts should be made to avoid refreezing or trauma, as this could worsen the initial injury.² Oral or intravenous hydration may be offered to optimize fluid status.¹ Supplemental oxygen may be administered to maintain saturations above 90%.¹ Nonsteroidal anti-inflammatory drugs are helpful for analgesia and anti-­inflammatory effect, and opioids can be used for breakthrough pain.¹ It is recommended that blisters be drained in a sterile fashion and that all affected tissue be covered with topical aloe vera and a loose dressing.^1,2,4

Treatment of severe frostbite. Angiography should be performed on all patients with third- or fourth-degree frostbite.³ If imaging shows evidence of vascular occlusion, tissue plasminogen activator (tPA) and heparin can be initiated within 24 hours to reduce the risk for amputation.^8-10

Continue to: Iloprost is another...

Iloprost is another proposed treatment for severe frostbite. It is a prostacyclin analog that may lower the amputation rate in patients with at least third-degree frostbite.¹¹ Unlike tPA, iloprost may be given to trauma patients, and it can be used more than 24 hours after injury.²

In cases of fourth-degree frostbite that is not successfully reperfused, amputation is delayed until dry gangrene develops. This often takes weeks to months.¹²

Our patient underwent rewarming and was orally rehydrated. He was discharged home with ibuprofen, oxycodone-­acetaminophen, topical aloe vera, and loose dressings. His bullae enlarged the next day (FIGURE 3). One week later, his blisters were debrided and dressed with silver sulfadiazine at his plastic surgery follow-up. He experienced sensory deficits for a few months, but eventually made a full recovery after 6 months with no remaining sequelae.

IMAGE COURTESY OF MORTEZA KHODAEE, MD, MPH

ACKNOWLEDGEMENT
The authors thank Lisa Kim, MD, for her clinical care of this patient.

CORRESPONDENCE
Morteza Khodaee, MD, MPH, University of Colorado School of Medicine, Department of Family Medicine, AFW Clinic, 3055 Roslyn Street, Denver, CO 80238; morteza.khodaee@ cuanschutz.edu

ILLUSTRATIVE CASE

A 27-year-old G1P000 at term with an uncomplicated pregnancy has been laboring for 6 hours with an epidural in place and a reassuring fetal heart tracing. She is at –2 station with complete cervical dilation and effacement. Should she push now or delay pushing to allow for more descent?

More than 10,000 women give birth each day in the United States, yet few of our approaches to labor management are evidence based.² For example, there are no clear guidelines on whether immediate pushing or delayed pushing (waiting 1-2 hours) in the second stage of labor (the time from complete cervical dilation to delivery of the fetus) leads to better outcomes.

A recent Cochrane review, which included very low- to moderate-quality trials of nulliparous and multiparous women using epidural analgesia showed that delayed pushing resulted in more vaginal deliveries, longer duration of second stage of labor, and shorter duration of pushing.³ But many of the trials included in this Cochrane review were noted to have study design limitations and significant heterogeneity.

A recent retrospective study found that delayed pushing resulted in longer duration of pushing and increased risks for cesarean section, operative vaginal delivery, and postpartum hemorrhage in nulliparous patients with and without epidurals.⁴ The World Health Organization recommends delayed pushing in women with epidural analgesia if time and fetal monitoring resources are available.⁵

STUDY SUMMARY

Does the timing of second stage pushing efforts affect outcomes?

This multicenter randomized controlled trial (RCT) evaluated the effect on spontaneous vaginal delivery of delayed pushing vs immediate pushing in 2404 term nulliparous women using epidural analgesia.¹ Patients were ≥ 37 weeks’ gestation. Once patients achieved 10 cm of cervical dilation, they were randomized in a 1:1 ratio to either immediate pushing or to delayed (for 60 minutes) pushing (unless there was an irresistible urge to push or they were otherwise instructed by their provider).

Outcome and results. The primary outcome was spontaneous vaginal delivery without the use of any operative support. The mean time to pushing after complete cervical dilation was 19 minutes in the immediate pushing group and 60 minutes in the delayed group. There was no difference in the rate of spontaneous vaginal delivery between the immediate and delayed pushing groups (86% vs 87%, respectively; P = .67). The immediate pushing group had a shorter duration of second stage of labor (102 minutes vs 134 minutes; mean difference [MD] = –32 minutes; 95% confidence interval [CI], –37 to –27; P < .001) and a slightly longer duration of active pushing (84 minutes vs 75 minutes; MD = 9.2 minutes; 95% CI, 6-13; P < .001).

Delaying pushing once the cervix is completely dilated is not indicated, even for nulliparous women receiving epidural analgesia.

There was no significant difference in operative vaginal or cesarean deliveries. Postpartum hemorrhage was lower in the immediate pushing group (2.3% vs 4%; risk ratio [RR] = 0.6; 95% CI, 0.3-0.9; P = .03; number needed to treat [NNT] = 58), as was chorioamnionitis (6.7% vs 9.1%; RR = 0.7; 95% CI, 0.66-0.90; P = .005; NNT = 40). There was no significant difference in neonatal morbidity between groups. And in subgroup analysis, there was no significant difference in rates of vaginal delivery based on fetal position (occiput anterior, posterior, or transverse) or station (defined as high [< 2 cm] or low [≥ 2 cm]) between groups. Recruitment was stopped early at 75% because there was no difference in the primary outcome and there was concern regarding an increased risk of hemorrhage in the delayed pushing group.

Continue to: WHAT'S NEW

WHAT’S NEW

There’s no good reason to delay pushing

Delaying pushing once the cervix is completely dilated is not indicated, even for nulliparous women receiving epidural analgesia, as it does not decrease the rate of spontaneous vaginal delivery. It does, however, increase the length of second stage labor and the risk of postpartum hemorrhage and chorioamnionitis.

CAVEATS

Study was stopped early, and groups were unblinded

This study was stopped early, so it is not known if it was underpowered for some of the secondary outcomes. Also, it was not possible to blind the groups, so it is not clear if any bias in patient management or diagnosis resulted.

CHALLENGES TO IMPLEMENTATION

Will current practice and culture pose obstacles?

Although the overt challenges to enacting a policy of immediate pushing are minimal, the inertia of current practice and culture could affect the implementation of this strategy.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 27-year-old G1P000 at term with an uncomplicated pregnancy has been laboring for 6 hours with an epidural in place and a reassuring fetal heart tracing. She is at –2 station with complete cervical dilation and effacement. Should she push now or delay pushing to allow for more descent?

More than 10,000 women give birth each day in the United States, yet few of our approaches to labor management are evidence based.² For example, there are no clear guidelines on whether immediate pushing or delayed pushing (waiting 1-2 hours) in the second stage of labor (the time from complete cervical dilation to delivery of the fetus) leads to better outcomes.

A recent Cochrane review, which included very low- to moderate-quality trials of nulliparous and multiparous women using epidural analgesia showed that delayed pushing resulted in more vaginal deliveries, longer duration of second stage of labor, and shorter duration of pushing.³ But many of the trials included in this Cochrane review were noted to have study design limitations and significant heterogeneity.

A recent retrospective study found that delayed pushing resulted in longer duration of pushing and increased risks for cesarean section, operative vaginal delivery, and postpartum hemorrhage in nulliparous patients with and without epidurals.⁴ The World Health Organization recommends delayed pushing in women with epidural analgesia if time and fetal monitoring resources are available.⁵

STUDY SUMMARY

Does the timing of second stage pushing efforts affect outcomes?

This multicenter randomized controlled trial (RCT) evaluated the effect on spontaneous vaginal delivery of delayed pushing vs immediate pushing in 2404 term nulliparous women using epidural analgesia.¹ Patients were ≥ 37 weeks’ gestation. Once patients achieved 10 cm of cervical dilation, they were randomized in a 1:1 ratio to either immediate pushing or to delayed (for 60 minutes) pushing (unless there was an irresistible urge to push or they were otherwise instructed by their provider).

Outcome and results. The primary outcome was spontaneous vaginal delivery without the use of any operative support. The mean time to pushing after complete cervical dilation was 19 minutes in the immediate pushing group and 60 minutes in the delayed group. There was no difference in the rate of spontaneous vaginal delivery between the immediate and delayed pushing groups (86% vs 87%, respectively; P = .67). The immediate pushing group had a shorter duration of second stage of labor (102 minutes vs 134 minutes; mean difference [MD] = –32 minutes; 95% confidence interval [CI], –37 to –27; P < .001) and a slightly longer duration of active pushing (84 minutes vs 75 minutes; MD = 9.2 minutes; 95% CI, 6-13; P < .001).

Delaying pushing once the cervix is completely dilated is not indicated, even for nulliparous women receiving epidural analgesia.

There was no significant difference in operative vaginal or cesarean deliveries. Postpartum hemorrhage was lower in the immediate pushing group (2.3% vs 4%; risk ratio [RR] = 0.6; 95% CI, 0.3-0.9; P = .03; number needed to treat [NNT] = 58), as was chorioamnionitis (6.7% vs 9.1%; RR = 0.7; 95% CI, 0.66-0.90; P = .005; NNT = 40). There was no significant difference in neonatal morbidity between groups. And in subgroup analysis, there was no significant difference in rates of vaginal delivery based on fetal position (occiput anterior, posterior, or transverse) or station (defined as high [< 2 cm] or low [≥ 2 cm]) between groups. Recruitment was stopped early at 75% because there was no difference in the primary outcome and there was concern regarding an increased risk of hemorrhage in the delayed pushing group.

Continue to: WHAT'S NEW

WHAT’S NEW

There’s no good reason to delay pushing

Delaying pushing once the cervix is completely dilated is not indicated, even for nulliparous women receiving epidural analgesia, as it does not decrease the rate of spontaneous vaginal delivery. It does, however, increase the length of second stage labor and the risk of postpartum hemorrhage and chorioamnionitis.

CAVEATS

Study was stopped early, and groups were unblinded

This study was stopped early, so it is not known if it was underpowered for some of the secondary outcomes. Also, it was not possible to blind the groups, so it is not clear if any bias in patient management or diagnosis resulted.

CHALLENGES TO IMPLEMENTATION

Will current practice and culture pose obstacles?

Although the overt challenges to enacting a policy of immediate pushing are minimal, the inertia of current practice and culture could affect the implementation of this strategy.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 27-year-old G1P000 at term with an uncomplicated pregnancy has been laboring for 6 hours with an epidural in place and a reassuring fetal heart tracing. She is at –2 station with complete cervical dilation and effacement. Should she push now or delay pushing to allow for more descent?

More than 10,000 women give birth each day in the United States, yet few of our approaches to labor management are evidence based.² For example, there are no clear guidelines on whether immediate pushing or delayed pushing (waiting 1-2 hours) in the second stage of labor (the time from complete cervical dilation to delivery of the fetus) leads to better outcomes.

A recent Cochrane review, which included very low- to moderate-quality trials of nulliparous and multiparous women using epidural analgesia showed that delayed pushing resulted in more vaginal deliveries, longer duration of second stage of labor, and shorter duration of pushing.³ But many of the trials included in this Cochrane review were noted to have study design limitations and significant heterogeneity.

A recent retrospective study found that delayed pushing resulted in longer duration of pushing and increased risks for cesarean section, operative vaginal delivery, and postpartum hemorrhage in nulliparous patients with and without epidurals.⁴ The World Health Organization recommends delayed pushing in women with epidural analgesia if time and fetal monitoring resources are available.⁵

STUDY SUMMARY

Does the timing of second stage pushing efforts affect outcomes?

This multicenter randomized controlled trial (RCT) evaluated the effect on spontaneous vaginal delivery of delayed pushing vs immediate pushing in 2404 term nulliparous women using epidural analgesia.¹ Patients were ≥ 37 weeks’ gestation. Once patients achieved 10 cm of cervical dilation, they were randomized in a 1:1 ratio to either immediate pushing or to delayed (for 60 minutes) pushing (unless there was an irresistible urge to push or they were otherwise instructed by their provider).

Outcome and results. The primary outcome was spontaneous vaginal delivery without the use of any operative support. The mean time to pushing after complete cervical dilation was 19 minutes in the immediate pushing group and 60 minutes in the delayed group. There was no difference in the rate of spontaneous vaginal delivery between the immediate and delayed pushing groups (86% vs 87%, respectively; P = .67). The immediate pushing group had a shorter duration of second stage of labor (102 minutes vs 134 minutes; mean difference [MD] = –32 minutes; 95% confidence interval [CI], –37 to –27; P < .001) and a slightly longer duration of active pushing (84 minutes vs 75 minutes; MD = 9.2 minutes; 95% CI, 6-13; P < .001).

Delaying pushing once the cervix is completely dilated is not indicated, even for nulliparous women receiving epidural analgesia.

There was no significant difference in operative vaginal or cesarean deliveries. Postpartum hemorrhage was lower in the immediate pushing group (2.3% vs 4%; risk ratio [RR] = 0.6; 95% CI, 0.3-0.9; P = .03; number needed to treat [NNT] = 58), as was chorioamnionitis (6.7% vs 9.1%; RR = 0.7; 95% CI, 0.66-0.90; P = .005; NNT = 40). There was no significant difference in neonatal morbidity between groups. And in subgroup analysis, there was no significant difference in rates of vaginal delivery based on fetal position (occiput anterior, posterior, or transverse) or station (defined as high [< 2 cm] or low [≥ 2 cm]) between groups. Recruitment was stopped early at 75% because there was no difference in the primary outcome and there was concern regarding an increased risk of hemorrhage in the delayed pushing group.

Continue to: WHAT'S NEW

WHAT’S NEW

There’s no good reason to delay pushing

Delaying pushing once the cervix is completely dilated is not indicated, even for nulliparous women receiving epidural analgesia, as it does not decrease the rate of spontaneous vaginal delivery. It does, however, increase the length of second stage labor and the risk of postpartum hemorrhage and chorioamnionitis.

CAVEATS

Study was stopped early, and groups were unblinded

This study was stopped early, so it is not known if it was underpowered for some of the secondary outcomes. Also, it was not possible to blind the groups, so it is not clear if any bias in patient management or diagnosis resulted.

CHALLENGES TO IMPLEMENTATION

Will current practice and culture pose obstacles?

Although the overt challenges to enacting a policy of immediate pushing are minimal, the inertia of current practice and culture could affect the implementation of this strategy.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Too few patients are being screened for abdominal aortic aneurysm (AAA), resulting in severe morbidity and mortality. Many patients with AAA aren’t identified until they present with rupture, leading to mortality as high as 90%.¹ Early detection is critical.

Medicare offers one-time free screening to eligible individuals > 65 years of age, and several professional organizations promote screening with published guidelines, which we discuss later in this article.

So who is at risk, who should be screened, and what is the best way to screen your patients?

Risk factors and sex differences

AAA has a prevalence of between 1% and 5% in men > 65 years old,^2,3 and it is 4 to 6 times more common in men than women.⁴ Major risk factors include smoking, older age, family history, and genetic factors, while hypertension, history of coronary artery disease, hyperlipidemia, and peripheral arterial disease have weaker associations.^3,4 Exercise and diabetes seem to have protective effects.⁵

The incidence and mortality of AAA increased between the 1950s and the mid-1990s; however, both indicators have decreased in numerous countries in the 21st century.⁶ Although the prevalence is much lower in women, they have a higher risk of rupture than men at equivalent lesion diameters.³ The prevalence of AAA in women who smoke and are > 70 years of age is > 1%.³

Silent but deadly

Most patients with AAA are asymptomatic. Their lesions are often detected incidentally on magnetic resonance imaging of the spine obtained for back pain, on an abdominal ultrasound (US) for gallstones, or on a routine computed tomography (CT) scan for the evaluation of abdominal pain. Some patients will experience vague abdominal discomfort from rapid expansion of an aneurysm prior to rupture, necessitating urgent repair. Also, some large aneurysms can erode into the spine and cause chronic back pain prior to rupture. An infrarenal abdominal aortic diameter > 30 mm defines an aneurysm,⁷ and once the diameter reaches 55 mm, the threat of rupture often justifies operative repair. (See “The preferred approach to repair.”)

Ruptured aneurysms will classically manifest with severe abdominal and/or back pain. Often a ruptured aneurysm will be contained in the retroperitoneum, allowing the patient to remain hemodynamically stable for a period of time and thus providing a window of opportunity for emergent repair.

Continue to: What is the evidence that screening is effective?

In 1988, researchers in Chichester, England, randomized > 6000 men ages 65 to 80 years to either a control group or a group that was offered a one-time US screen for AAA. After 15 years of follow-up, no significant difference in AAA mortality was seen between the groups, although 26% of those invited for screening declined to participate and accounted for more than half of the AAA-related deaths in the group receiving an invitation for screening.⁸

The MASS Trial,⁹ another British study, began in 1997 and screened men ages 65 to 74. More than 67,000 men were randomized, with 1 group invited for AAA screening and the other serving as a control. The final report on this trial was published in 2012. After 13 years of follow-up, there was a 42% reduction in AAA-related deaths in the group invited for screening, a small reduction in all-cause mortality, and a significant reduction in risk of AAA rupture (hazard ratio = 0.57). The researchers noted that 216 patients would have to be invited for screening to prevent 1 death over 13 years. They also reported that 21% of the invited patients that had an AAA-related death had an initial scan that was negative for AAA (aortic diameter < 3 cm). However, despite this finding, screening still appeared to be beneficial.

Lindholdt et al¹⁰ randomized > 12,000 Danish men ages 64 to 73 to serve as controls or to be invited for US screening for AAA. After 13 years of follow-up, those invited for screening had a 66% relative risk reduction in AAA-related mortality, with screening considered cost effective. There were no differences between the groups in all-cause mortality. Conversely, the Western Australia Trial studied an older group of men, ages 64 to 83, but was unable to show a benefit of screening in lowering AAA-related mortality.¹¹

Tikagi et al⁶ performed a meta-analysis on the data from the 4 trials above and reported up to 15 years of follow-up. Patients who attended screening sessions had a reduction in all-cause mortality with an odds ratio (OR) of 0.6, and a marked reduction in AAA-­related mortality with an OR of 0.4. The favorable data on screening have prompted the United Kingdom and Sweden to offer screening to all men ≥ 65 years, based on the current estimate of a 1% prevalence of AAA, although screening is felt to remain cost effective down to a prevalence of 0.35%.¹²

Handheld ultrasound is a viable method to detect AAA in an outpatient primary care setting at a reasonable cost.

Massachusetts General Hospital also reported¹³ that the detection rate of AAA increased, with the diagnosis made at smaller aneurysm dimensions, following publication of the US Preventive Services Task Force recommendations (reviewed below).

Continue to: When to screen

When to screen

Several professional organizations, as well as Medicare, have published AAA screening recommendations. While there are notable differences among them, their shared message is crucial: screen. Consider adding applicable reminders to your practice’s electronic medical record system to increase screening rates for eligible patients.

US Preventive Services Task Force ¹⁴

• Recommend one-time AAA screening with ultrasonography for men ages 65 to 75 years who have ever smoked (B recommendation).
• Selectively offer AAA screening to men ages 65 to 75 years who have never smoked, rather than routinely screening all men in this group (C recommendation). Individual attributes that could favor screening include a family history of AAA, the presence of other arterial aneurysms, and the number of risk factors for cardiovascular disease.
• Do not routinely screen women for AAA if they have never smoked and have no family history of AAA (D recommendation). For women ages 65 to 75 years who have ever smoked or have a family history of AAA, current evidence is insufficient to assess the balance of benefits and harms of screening for AAA (I statement). (See the related Practice Alert.)

Canadian Task Force on Preventive Health Care⁴

• Recommend one-time screening for AAA with US for men 65 to 80 years of age (weak level of recommendation; moderate-quality evidence).
• Do not recommend screening for men older than 80 years of age (weak recommendation; low quality of evidence).
• Do not recommend screening for women (strong recommendation; very low quality of evidence).

Society for Vascular Surgery¹⁵

• Recommend one-time US screening for AAA for men or women 65 to 75 years of age with a history of tobacco use (strong recommendation with high-quality evidence).
• Recommend one-time screening if there is a history of smoking for men or women > 75 years of age who are in good health and have not previously been screened. (Weak recommendation with low-quality evidence).
• Recommend one-time screening of men or women 65 to 75 years of age who are first-degree relatives of someone with AAA, or in those older than age 75 and in good health (weak recommendation with low-quality evidence).

How to screen

Physical exam. The abdominal aorta is often palpable in the epigastric region, and a thorough abdominal exam should include an attempt to detect it. It is critical that the patient be supine during palpation, to allow compression of the aorta against the lumbar spine. Even with a well-performed exam, however, its sensitivity is just 76% in the detection of AAA ≥ 5 cm.¹⁶

Continue to: Imaging

Imaging. US is the preferred imaging procedure when screening for AAA, given its high sensitivity and specificity.¹⁷ If US yields poor image quality, noncontrast CT is suggested, with magnetic resonance angiography being another alternative.¹⁸ Handheld US has the potential to supplement the physical exam, and has been shown to be a viable method to detect AAA in an outpatient primary care setting at a reasonable cost.¹⁹ Typically, a formal aortic US requires a patient to go without food or liquids for 8 hours before the procedure to obtain the best image; however, a good estimate of aortic diameter can be obtained without this restriction.

Despite Medicare coverage and recs, few people are screened

In 2007, Medicare started the SAAVE Program (Screening Aortic Aneurysm Very Effectively), offering a one-time US screening for AAA for eligible patients, as part of the Welcome to Medicare Program. Eligible individuals are men between 65 and 75 years of age with a history of smoking at least 100 cigarettes in their lifetime, and men or women in the same age group with a family history of AAA.²

Despite these recommendations, few patients receive screening. Centers for Medicare & Medicaid Services data show that < 10% of eligible men were screened between 2004 and 2008,²⁰ and Olchanski et al²¹ report that < 1% of eligible patients were screened from 2005-2009. A simulation model estimates that 131 additional life years could be gained per 1000 patients screened if the utilization rate could be increased to 80%, a seemingly achievable goal.²¹ Moreover, expanding the screening program to include female smokers could increase 10-year life expectancy by 13%.²¹ Reasons for underutilization of this Medicare screening benefit may include lack of awareness by physicians and patients, costs of co-pays, and underutilization of the basic Welcome to Medicare exam.²¹

An additional consequence of low utilization of AAA screening is a high percentage of patients who are identified only late in the course of the disease. Mell et al²² report that 39% of patients undergoing AAA repair were identified < 6 months prior to surgery, a higher percentage than would be expected in a well-screened population. They also determined that slightly more than one-third of patients undergoing surgery for ruptured AAA had diagnostic imaging performed > 6 months prior to surgery, suggesting the possibility that these patients may not have been properly surveilled for aneurysm expansion, although the authors note that other potential explanations include delays in treatment due to comorbidities, and patient-related factors such as refusal of surgery or noncompliance with follow-up.

CORRESPONDENCE
Jeffrey S. Todd, MD, 127 McClanahan Street, Suite 300, Roanoke, VA 24014; jstodd@carilionclinic.org.

Too few patients are being screened for abdominal aortic aneurysm (AAA), resulting in severe morbidity and mortality. Many patients with AAA aren’t identified until they present with rupture, leading to mortality as high as 90%.¹ Early detection is critical.

Medicare offers one-time free screening to eligible individuals > 65 years of age, and several professional organizations promote screening with published guidelines, which we discuss later in this article.

So who is at risk, who should be screened, and what is the best way to screen your patients?

Risk factors and sex differences

AAA has a prevalence of between 1% and 5% in men > 65 years old,^2,3 and it is 4 to 6 times more common in men than women.⁴ Major risk factors include smoking, older age, family history, and genetic factors, while hypertension, history of coronary artery disease, hyperlipidemia, and peripheral arterial disease have weaker associations.^3,4 Exercise and diabetes seem to have protective effects.⁵

The incidence and mortality of AAA increased between the 1950s and the mid-1990s; however, both indicators have decreased in numerous countries in the 21st century.⁶ Although the prevalence is much lower in women, they have a higher risk of rupture than men at equivalent lesion diameters.³ The prevalence of AAA in women who smoke and are > 70 years of age is > 1%.³

Silent but deadly

Most patients with AAA are asymptomatic. Their lesions are often detected incidentally on magnetic resonance imaging of the spine obtained for back pain, on an abdominal ultrasound (US) for gallstones, or on a routine computed tomography (CT) scan for the evaluation of abdominal pain. Some patients will experience vague abdominal discomfort from rapid expansion of an aneurysm prior to rupture, necessitating urgent repair. Also, some large aneurysms can erode into the spine and cause chronic back pain prior to rupture. An infrarenal abdominal aortic diameter > 30 mm defines an aneurysm,⁷ and once the diameter reaches 55 mm, the threat of rupture often justifies operative repair. (See “The preferred approach to repair.”)

Ruptured aneurysms will classically manifest with severe abdominal and/or back pain. Often a ruptured aneurysm will be contained in the retroperitoneum, allowing the patient to remain hemodynamically stable for a period of time and thus providing a window of opportunity for emergent repair.

Continue to: What is the evidence that screening is effective?

In 1988, researchers in Chichester, England, randomized > 6000 men ages 65 to 80 years to either a control group or a group that was offered a one-time US screen for AAA. After 15 years of follow-up, no significant difference in AAA mortality was seen between the groups, although 26% of those invited for screening declined to participate and accounted for more than half of the AAA-related deaths in the group receiving an invitation for screening.⁸

The MASS Trial,⁹ another British study, began in 1997 and screened men ages 65 to 74. More than 67,000 men were randomized, with 1 group invited for AAA screening and the other serving as a control. The final report on this trial was published in 2012. After 13 years of follow-up, there was a 42% reduction in AAA-related deaths in the group invited for screening, a small reduction in all-cause mortality, and a significant reduction in risk of AAA rupture (hazard ratio = 0.57). The researchers noted that 216 patients would have to be invited for screening to prevent 1 death over 13 years. They also reported that 21% of the invited patients that had an AAA-related death had an initial scan that was negative for AAA (aortic diameter < 3 cm). However, despite this finding, screening still appeared to be beneficial.

Lindholdt et al¹⁰ randomized > 12,000 Danish men ages 64 to 73 to serve as controls or to be invited for US screening for AAA. After 13 years of follow-up, those invited for screening had a 66% relative risk reduction in AAA-related mortality, with screening considered cost effective. There were no differences between the groups in all-cause mortality. Conversely, the Western Australia Trial studied an older group of men, ages 64 to 83, but was unable to show a benefit of screening in lowering AAA-related mortality.¹¹

Tikagi et al⁶ performed a meta-analysis on the data from the 4 trials above and reported up to 15 years of follow-up. Patients who attended screening sessions had a reduction in all-cause mortality with an odds ratio (OR) of 0.6, and a marked reduction in AAA-­related mortality with an OR of 0.4. The favorable data on screening have prompted the United Kingdom and Sweden to offer screening to all men ≥ 65 years, based on the current estimate of a 1% prevalence of AAA, although screening is felt to remain cost effective down to a prevalence of 0.35%.¹²

Handheld ultrasound is a viable method to detect AAA in an outpatient primary care setting at a reasonable cost.

Massachusetts General Hospital also reported¹³ that the detection rate of AAA increased, with the diagnosis made at smaller aneurysm dimensions, following publication of the US Preventive Services Task Force recommendations (reviewed below).

Continue to: When to screen

When to screen

Several professional organizations, as well as Medicare, have published AAA screening recommendations. While there are notable differences among them, their shared message is crucial: screen. Consider adding applicable reminders to your practice’s electronic medical record system to increase screening rates for eligible patients.

US Preventive Services Task Force ¹⁴

• Recommend one-time AAA screening with ultrasonography for men ages 65 to 75 years who have ever smoked (B recommendation).
• Selectively offer AAA screening to men ages 65 to 75 years who have never smoked, rather than routinely screening all men in this group (C recommendation). Individual attributes that could favor screening include a family history of AAA, the presence of other arterial aneurysms, and the number of risk factors for cardiovascular disease.
• Do not routinely screen women for AAA if they have never smoked and have no family history of AAA (D recommendation). For women ages 65 to 75 years who have ever smoked or have a family history of AAA, current evidence is insufficient to assess the balance of benefits and harms of screening for AAA (I statement). (See the related Practice Alert.)

Canadian Task Force on Preventive Health Care⁴

• Recommend one-time screening for AAA with US for men 65 to 80 years of age (weak level of recommendation; moderate-quality evidence).
• Do not recommend screening for men older than 80 years of age (weak recommendation; low quality of evidence).
• Do not recommend screening for women (strong recommendation; very low quality of evidence).

Society for Vascular Surgery¹⁵

• Recommend one-time US screening for AAA for men or women 65 to 75 years of age with a history of tobacco use (strong recommendation with high-quality evidence).
• Recommend one-time screening if there is a history of smoking for men or women > 75 years of age who are in good health and have not previously been screened. (Weak recommendation with low-quality evidence).
• Recommend one-time screening of men or women 65 to 75 years of age who are first-degree relatives of someone with AAA, or in those older than age 75 and in good health (weak recommendation with low-quality evidence).

How to screen

Physical exam. The abdominal aorta is often palpable in the epigastric region, and a thorough abdominal exam should include an attempt to detect it. It is critical that the patient be supine during palpation, to allow compression of the aorta against the lumbar spine. Even with a well-performed exam, however, its sensitivity is just 76% in the detection of AAA ≥ 5 cm.¹⁶

Continue to: Imaging

Imaging. US is the preferred imaging procedure when screening for AAA, given its high sensitivity and specificity.¹⁷ If US yields poor image quality, noncontrast CT is suggested, with magnetic resonance angiography being another alternative.¹⁸ Handheld US has the potential to supplement the physical exam, and has been shown to be a viable method to detect AAA in an outpatient primary care setting at a reasonable cost.¹⁹ Typically, a formal aortic US requires a patient to go without food or liquids for 8 hours before the procedure to obtain the best image; however, a good estimate of aortic diameter can be obtained without this restriction.

Despite Medicare coverage and recs, few people are screened

In 2007, Medicare started the SAAVE Program (Screening Aortic Aneurysm Very Effectively), offering a one-time US screening for AAA for eligible patients, as part of the Welcome to Medicare Program. Eligible individuals are men between 65 and 75 years of age with a history of smoking at least 100 cigarettes in their lifetime, and men or women in the same age group with a family history of AAA.²

Despite these recommendations, few patients receive screening. Centers for Medicare & Medicaid Services data show that < 10% of eligible men were screened between 2004 and 2008,²⁰ and Olchanski et al²¹ report that < 1% of eligible patients were screened from 2005-2009. A simulation model estimates that 131 additional life years could be gained per 1000 patients screened if the utilization rate could be increased to 80%, a seemingly achievable goal.²¹ Moreover, expanding the screening program to include female smokers could increase 10-year life expectancy by 13%.²¹ Reasons for underutilization of this Medicare screening benefit may include lack of awareness by physicians and patients, costs of co-pays, and underutilization of the basic Welcome to Medicare exam.²¹

An additional consequence of low utilization of AAA screening is a high percentage of patients who are identified only late in the course of the disease. Mell et al²² report that 39% of patients undergoing AAA repair were identified < 6 months prior to surgery, a higher percentage than would be expected in a well-screened population. They also determined that slightly more than one-third of patients undergoing surgery for ruptured AAA had diagnostic imaging performed > 6 months prior to surgery, suggesting the possibility that these patients may not have been properly surveilled for aneurysm expansion, although the authors note that other potential explanations include delays in treatment due to comorbidities, and patient-related factors such as refusal of surgery or noncompliance with follow-up.

CORRESPONDENCE
Jeffrey S. Todd, MD, 127 McClanahan Street, Suite 300, Roanoke, VA 24014; jstodd@carilionclinic.org.

Too few patients are being screened for abdominal aortic aneurysm (AAA), resulting in severe morbidity and mortality. Many patients with AAA aren’t identified until they present with rupture, leading to mortality as high as 90%.¹ Early detection is critical.

Medicare offers one-time free screening to eligible individuals > 65 years of age, and several professional organizations promote screening with published guidelines, which we discuss later in this article.

So who is at risk, who should be screened, and what is the best way to screen your patients?

Risk factors and sex differences

AAA has a prevalence of between 1% and 5% in men > 65 years old,^2,3 and it is 4 to 6 times more common in men than women.⁴ Major risk factors include smoking, older age, family history, and genetic factors, while hypertension, history of coronary artery disease, hyperlipidemia, and peripheral arterial disease have weaker associations.^3,4 Exercise and diabetes seem to have protective effects.⁵

The incidence and mortality of AAA increased between the 1950s and the mid-1990s; however, both indicators have decreased in numerous countries in the 21st century.⁶ Although the prevalence is much lower in women, they have a higher risk of rupture than men at equivalent lesion diameters.³ The prevalence of AAA in women who smoke and are > 70 years of age is > 1%.³

Silent but deadly

Most patients with AAA are asymptomatic. Their lesions are often detected incidentally on magnetic resonance imaging of the spine obtained for back pain, on an abdominal ultrasound (US) for gallstones, or on a routine computed tomography (CT) scan for the evaluation of abdominal pain. Some patients will experience vague abdominal discomfort from rapid expansion of an aneurysm prior to rupture, necessitating urgent repair. Also, some large aneurysms can erode into the spine and cause chronic back pain prior to rupture. An infrarenal abdominal aortic diameter > 30 mm defines an aneurysm,⁷ and once the diameter reaches 55 mm, the threat of rupture often justifies operative repair. (See “The preferred approach to repair.”)

Ruptured aneurysms will classically manifest with severe abdominal and/or back pain. Often a ruptured aneurysm will be contained in the retroperitoneum, allowing the patient to remain hemodynamically stable for a period of time and thus providing a window of opportunity for emergent repair.

Continue to: What is the evidence that screening is effective?

In 1988, researchers in Chichester, England, randomized > 6000 men ages 65 to 80 years to either a control group or a group that was offered a one-time US screen for AAA. After 15 years of follow-up, no significant difference in AAA mortality was seen between the groups, although 26% of those invited for screening declined to participate and accounted for more than half of the AAA-related deaths in the group receiving an invitation for screening.⁸

The MASS Trial,⁹ another British study, began in 1997 and screened men ages 65 to 74. More than 67,000 men were randomized, with 1 group invited for AAA screening and the other serving as a control. The final report on this trial was published in 2012. After 13 years of follow-up, there was a 42% reduction in AAA-related deaths in the group invited for screening, a small reduction in all-cause mortality, and a significant reduction in risk of AAA rupture (hazard ratio = 0.57). The researchers noted that 216 patients would have to be invited for screening to prevent 1 death over 13 years. They also reported that 21% of the invited patients that had an AAA-related death had an initial scan that was negative for AAA (aortic diameter < 3 cm). However, despite this finding, screening still appeared to be beneficial.

Lindholdt et al¹⁰ randomized > 12,000 Danish men ages 64 to 73 to serve as controls or to be invited for US screening for AAA. After 13 years of follow-up, those invited for screening had a 66% relative risk reduction in AAA-related mortality, with screening considered cost effective. There were no differences between the groups in all-cause mortality. Conversely, the Western Australia Trial studied an older group of men, ages 64 to 83, but was unable to show a benefit of screening in lowering AAA-related mortality.¹¹

Tikagi et al⁶ performed a meta-analysis on the data from the 4 trials above and reported up to 15 years of follow-up. Patients who attended screening sessions had a reduction in all-cause mortality with an odds ratio (OR) of 0.6, and a marked reduction in AAA-­related mortality with an OR of 0.4. The favorable data on screening have prompted the United Kingdom and Sweden to offer screening to all men ≥ 65 years, based on the current estimate of a 1% prevalence of AAA, although screening is felt to remain cost effective down to a prevalence of 0.35%.¹²

Handheld ultrasound is a viable method to detect AAA in an outpatient primary care setting at a reasonable cost.

Massachusetts General Hospital also reported¹³ that the detection rate of AAA increased, with the diagnosis made at smaller aneurysm dimensions, following publication of the US Preventive Services Task Force recommendations (reviewed below).

Continue to: When to screen

When to screen

Several professional organizations, as well as Medicare, have published AAA screening recommendations. While there are notable differences among them, their shared message is crucial: screen. Consider adding applicable reminders to your practice’s electronic medical record system to increase screening rates for eligible patients.

US Preventive Services Task Force ¹⁴

• Recommend one-time AAA screening with ultrasonography for men ages 65 to 75 years who have ever smoked (B recommendation).
• Selectively offer AAA screening to men ages 65 to 75 years who have never smoked, rather than routinely screening all men in this group (C recommendation). Individual attributes that could favor screening include a family history of AAA, the presence of other arterial aneurysms, and the number of risk factors for cardiovascular disease.
• Do not routinely screen women for AAA if they have never smoked and have no family history of AAA (D recommendation). For women ages 65 to 75 years who have ever smoked or have a family history of AAA, current evidence is insufficient to assess the balance of benefits and harms of screening for AAA (I statement). (See the related Practice Alert.)

Canadian Task Force on Preventive Health Care⁴

• Recommend one-time screening for AAA with US for men 65 to 80 years of age (weak level of recommendation; moderate-quality evidence).
• Do not recommend screening for men older than 80 years of age (weak recommendation; low quality of evidence).
• Do not recommend screening for women (strong recommendation; very low quality of evidence).

Society for Vascular Surgery¹⁵

• Recommend one-time US screening for AAA for men or women 65 to 75 years of age with a history of tobacco use (strong recommendation with high-quality evidence).
• Recommend one-time screening if there is a history of smoking for men or women > 75 years of age who are in good health and have not previously been screened. (Weak recommendation with low-quality evidence).
• Recommend one-time screening of men or women 65 to 75 years of age who are first-degree relatives of someone with AAA, or in those older than age 75 and in good health (weak recommendation with low-quality evidence).

How to screen

Physical exam. The abdominal aorta is often palpable in the epigastric region, and a thorough abdominal exam should include an attempt to detect it. It is critical that the patient be supine during palpation, to allow compression of the aorta against the lumbar spine. Even with a well-performed exam, however, its sensitivity is just 76% in the detection of AAA ≥ 5 cm.¹⁶

Continue to: Imaging

Imaging. US is the preferred imaging procedure when screening for AAA, given its high sensitivity and specificity.¹⁷ If US yields poor image quality, noncontrast CT is suggested, with magnetic resonance angiography being another alternative.¹⁸ Handheld US has the potential to supplement the physical exam, and has been shown to be a viable method to detect AAA in an outpatient primary care setting at a reasonable cost.¹⁹ Typically, a formal aortic US requires a patient to go without food or liquids for 8 hours before the procedure to obtain the best image; however, a good estimate of aortic diameter can be obtained without this restriction.

Despite Medicare coverage and recs, few people are screened

In 2007, Medicare started the SAAVE Program (Screening Aortic Aneurysm Very Effectively), offering a one-time US screening for AAA for eligible patients, as part of the Welcome to Medicare Program. Eligible individuals are men between 65 and 75 years of age with a history of smoking at least 100 cigarettes in their lifetime, and men or women in the same age group with a family history of AAA.²

Despite these recommendations, few patients receive screening. Centers for Medicare & Medicaid Services data show that < 10% of eligible men were screened between 2004 and 2008,²⁰ and Olchanski et al²¹ report that < 1% of eligible patients were screened from 2005-2009. A simulation model estimates that 131 additional life years could be gained per 1000 patients screened if the utilization rate could be increased to 80%, a seemingly achievable goal.²¹ Moreover, expanding the screening program to include female smokers could increase 10-year life expectancy by 13%.²¹ Reasons for underutilization of this Medicare screening benefit may include lack of awareness by physicians and patients, costs of co-pays, and underutilization of the basic Welcome to Medicare exam.²¹

An additional consequence of low utilization of AAA screening is a high percentage of patients who are identified only late in the course of the disease. Mell et al²² report that 39% of patients undergoing AAA repair were identified < 6 months prior to surgery, a higher percentage than would be expected in a well-screened population. They also determined that slightly more than one-third of patients undergoing surgery for ruptured AAA had diagnostic imaging performed > 6 months prior to surgery, suggesting the possibility that these patients may not have been properly surveilled for aneurysm expansion, although the authors note that other potential explanations include delays in treatment due to comorbidities, and patient-related factors such as refusal of surgery or noncompliance with follow-up.

CORRESPONDENCE
Jeffrey S. Todd, MD, 127 McClanahan Street, Suite 300, Roanoke, VA 24014; jstodd@carilionclinic.org.