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Aortic repair in Loeys-Dietz syndrome requires close follow-up
The knowledge about Loeys-Dietz syndrome has evolved quickly since Hal Dietz, MD, and Bart Loeys, MD, at Johns Hopkins University, Baltimore, first reported on it in 2005.
Now, another team of Johns Hopkins investigators have reported that an aggressive approach with aortic root replacement coupled with valve-sparing whenever possible produces favorable results, but that clinicians must follow these patients closely with cardiovascular imaging.
“Growing experience with Loeys-Dietz syndrome has confirmed early impressions of its aggressive nature and proclivity toward aortic catastrophe,” Nishant D. Patel, MD, and his coauthors said in the February issue of the Journal of Thoracic and Cardiovascular Surgery (2017;153:406-12). They reported on results of all 79 patients with Loeys-Dietz syndrome (LDS) who had cardiovascular surgery at Johns Hopkins. There were two (3%) deaths during surgery and eight (10%) late deaths. Patients with LDS are at risk for dissection early when the aortic root reaches 4 cm. Despite what they termed “favorable” outcomes of surgery, Dr. Patel and his coauthors acknowledged that reintervention rates for this population are high – 19 patients (24%) had subsequent operations. That suggests cardiac surgeons must closely monitor these patients. “Meticulous follow-up with cardiovascular surveillance imaging remains important for management, particularly as clinical LDS subtypes are characterized and more tailored treatment is developed,” Dr. Patel and his coauthors reported.
They advise echocardiography every 3 to 6 months for the first year after surgery and then every 6 to 12 months afterward. Full-body imaging should occur at least every 2 years. “In particular, patients with type B dissections should be monitored aggressively for aneurysm growth,” Dr. Patel and his coauthors said. They recommend imaging at seven to 14 days after dissection, then repeat imaging at 1, 3, 6, and 12 months, and then yearly thereafter.
They noted that four LDS subtypes have been identified. Although those with LDS1 and 2 subtypes are prone to aortic rupture at an earlier age and at smaller aortic diameters than other connective tissue disorders, the medical and surgical management for all subtypes are similar, Dr. Patel and his coauthors indicated.
“Certain congenital heart defects are more common among patients with LDS, compared with the normal population, including patent ductus arteriosus and mitral valve prolapse/insufficiency,” they said. Genotype is one factor that determines the need for surgery in LDS patients, Dr. Patel and his coauthors said. Others are growth rate, aortic valve function, family history, and severity of noncardiac phenotype.
The 79 patients in the study were divided almost evenly between gender, and the average age at first operation was 24.9 years; 38 were children younger than 18 years and 20 had a previous sternotomy. Aortic root replacement represented the predominant operation in the group, accounting for 65 operations (82.3%), of which 52 (80%) were valve-sparing procedures and the remainder were composite valve-graft procedures. The other procedures the researchers performed were nine aortic arch replacements (11.4%), three open thoracoabdominal repairs (3.8%) and two ascending aorta replacements (2.5%).
“Valve-sparing root replacement has become a safe and reliable option for appropriately selected younger patients with LDS,” Dr. Patel and his coauthors wrote. Five patients needed a second operation on the aortic valve or root; three of them had a Florida sleeve procedure. “Based on these initial outcomes with the Florida sleeve at our institution, we have abandoned this procedure in favor of conventional valve-sparing root replacement,” Dr. Patel and his coauthors stated.
Dr. Patel and his coauthors had no financial relationships to disclose.
A rare disease such as Loeys-Dietz syndrome (LDS) seems more common now in vascular surgery, as we are the specialty making decisions on disorders of the descending thoracic aorta. Understanding not only the clinical presentation with the aortic root involvement but the fact that these patients require close surveillance is the key message.
Often we are consulted regarding or admit a patient with an acute type B dissection who usually has a history of poorly controlled hypertension but, also, has a history of “aneurysms” or a family member who passed away at a young age. These clues should lead us to explore the “molecular diagnosis” as well to see if patients have a connective tissue disorder such as LDS or vascular Ehlers-Danlos syndrome (vEDS). Because many of these syndromes have overlapping symptoms, understanding the type of connective tissue disorder will allow us to appreciate the differences, especially in a syndrome such as LDS, which was first reported in 2005 and is associated with more cardiac and aortic root pathologies than vEDS.
At the University of Washington, my colleague Dr. Sherene Shalhub heads a vascular genetics clinic in which she examines patients with potential connective tissue disorders in an attempt to make the molecular diagnosis and identify surveillance protocols and study the effect of open and endovascular repairs in these patients. Pooling data on these patients from around the country and collaborating within, as well as outside of, our specialty is imperative to increasing our understanding of these disorders. I believe we are seeing a trend in which we crave studies such as Dr. Patel’s to increase our knowledge on these rare (but now more common) entities.
Niten Singh, MD, is the director of the Limb Preservation Service at the Regional Vascular Center at Harborview Medical Center, Seattle, and an Associate Editor of Vascular Specialist.
A rare disease such as Loeys-Dietz syndrome (LDS) seems more common now in vascular surgery, as we are the specialty making decisions on disorders of the descending thoracic aorta. Understanding not only the clinical presentation with the aortic root involvement but the fact that these patients require close surveillance is the key message.
Often we are consulted regarding or admit a patient with an acute type B dissection who usually has a history of poorly controlled hypertension but, also, has a history of “aneurysms” or a family member who passed away at a young age. These clues should lead us to explore the “molecular diagnosis” as well to see if patients have a connective tissue disorder such as LDS or vascular Ehlers-Danlos syndrome (vEDS). Because many of these syndromes have overlapping symptoms, understanding the type of connective tissue disorder will allow us to appreciate the differences, especially in a syndrome such as LDS, which was first reported in 2005 and is associated with more cardiac and aortic root pathologies than vEDS.
At the University of Washington, my colleague Dr. Sherene Shalhub heads a vascular genetics clinic in which she examines patients with potential connective tissue disorders in an attempt to make the molecular diagnosis and identify surveillance protocols and study the effect of open and endovascular repairs in these patients. Pooling data on these patients from around the country and collaborating within, as well as outside of, our specialty is imperative to increasing our understanding of these disorders. I believe we are seeing a trend in which we crave studies such as Dr. Patel’s to increase our knowledge on these rare (but now more common) entities.
Niten Singh, MD, is the director of the Limb Preservation Service at the Regional Vascular Center at Harborview Medical Center, Seattle, and an Associate Editor of Vascular Specialist.
A rare disease such as Loeys-Dietz syndrome (LDS) seems more common now in vascular surgery, as we are the specialty making decisions on disorders of the descending thoracic aorta. Understanding not only the clinical presentation with the aortic root involvement but the fact that these patients require close surveillance is the key message.
Often we are consulted regarding or admit a patient with an acute type B dissection who usually has a history of poorly controlled hypertension but, also, has a history of “aneurysms” or a family member who passed away at a young age. These clues should lead us to explore the “molecular diagnosis” as well to see if patients have a connective tissue disorder such as LDS or vascular Ehlers-Danlos syndrome (vEDS). Because many of these syndromes have overlapping symptoms, understanding the type of connective tissue disorder will allow us to appreciate the differences, especially in a syndrome such as LDS, which was first reported in 2005 and is associated with more cardiac and aortic root pathologies than vEDS.
At the University of Washington, my colleague Dr. Sherene Shalhub heads a vascular genetics clinic in which she examines patients with potential connective tissue disorders in an attempt to make the molecular diagnosis and identify surveillance protocols and study the effect of open and endovascular repairs in these patients. Pooling data on these patients from around the country and collaborating within, as well as outside of, our specialty is imperative to increasing our understanding of these disorders. I believe we are seeing a trend in which we crave studies such as Dr. Patel’s to increase our knowledge on these rare (but now more common) entities.
Niten Singh, MD, is the director of the Limb Preservation Service at the Regional Vascular Center at Harborview Medical Center, Seattle, and an Associate Editor of Vascular Specialist.
The knowledge about Loeys-Dietz syndrome has evolved quickly since Hal Dietz, MD, and Bart Loeys, MD, at Johns Hopkins University, Baltimore, first reported on it in 2005.
Now, another team of Johns Hopkins investigators have reported that an aggressive approach with aortic root replacement coupled with valve-sparing whenever possible produces favorable results, but that clinicians must follow these patients closely with cardiovascular imaging.
“Growing experience with Loeys-Dietz syndrome has confirmed early impressions of its aggressive nature and proclivity toward aortic catastrophe,” Nishant D. Patel, MD, and his coauthors said in the February issue of the Journal of Thoracic and Cardiovascular Surgery (2017;153:406-12). They reported on results of all 79 patients with Loeys-Dietz syndrome (LDS) who had cardiovascular surgery at Johns Hopkins. There were two (3%) deaths during surgery and eight (10%) late deaths. Patients with LDS are at risk for dissection early when the aortic root reaches 4 cm. Despite what they termed “favorable” outcomes of surgery, Dr. Patel and his coauthors acknowledged that reintervention rates for this population are high – 19 patients (24%) had subsequent operations. That suggests cardiac surgeons must closely monitor these patients. “Meticulous follow-up with cardiovascular surveillance imaging remains important for management, particularly as clinical LDS subtypes are characterized and more tailored treatment is developed,” Dr. Patel and his coauthors reported.
They advise echocardiography every 3 to 6 months for the first year after surgery and then every 6 to 12 months afterward. Full-body imaging should occur at least every 2 years. “In particular, patients with type B dissections should be monitored aggressively for aneurysm growth,” Dr. Patel and his coauthors said. They recommend imaging at seven to 14 days after dissection, then repeat imaging at 1, 3, 6, and 12 months, and then yearly thereafter.
They noted that four LDS subtypes have been identified. Although those with LDS1 and 2 subtypes are prone to aortic rupture at an earlier age and at smaller aortic diameters than other connective tissue disorders, the medical and surgical management for all subtypes are similar, Dr. Patel and his coauthors indicated.
“Certain congenital heart defects are more common among patients with LDS, compared with the normal population, including patent ductus arteriosus and mitral valve prolapse/insufficiency,” they said. Genotype is one factor that determines the need for surgery in LDS patients, Dr. Patel and his coauthors said. Others are growth rate, aortic valve function, family history, and severity of noncardiac phenotype.
The 79 patients in the study were divided almost evenly between gender, and the average age at first operation was 24.9 years; 38 were children younger than 18 years and 20 had a previous sternotomy. Aortic root replacement represented the predominant operation in the group, accounting for 65 operations (82.3%), of which 52 (80%) were valve-sparing procedures and the remainder were composite valve-graft procedures. The other procedures the researchers performed were nine aortic arch replacements (11.4%), three open thoracoabdominal repairs (3.8%) and two ascending aorta replacements (2.5%).
“Valve-sparing root replacement has become a safe and reliable option for appropriately selected younger patients with LDS,” Dr. Patel and his coauthors wrote. Five patients needed a second operation on the aortic valve or root; three of them had a Florida sleeve procedure. “Based on these initial outcomes with the Florida sleeve at our institution, we have abandoned this procedure in favor of conventional valve-sparing root replacement,” Dr. Patel and his coauthors stated.
Dr. Patel and his coauthors had no financial relationships to disclose.
The knowledge about Loeys-Dietz syndrome has evolved quickly since Hal Dietz, MD, and Bart Loeys, MD, at Johns Hopkins University, Baltimore, first reported on it in 2005.
Now, another team of Johns Hopkins investigators have reported that an aggressive approach with aortic root replacement coupled with valve-sparing whenever possible produces favorable results, but that clinicians must follow these patients closely with cardiovascular imaging.
“Growing experience with Loeys-Dietz syndrome has confirmed early impressions of its aggressive nature and proclivity toward aortic catastrophe,” Nishant D. Patel, MD, and his coauthors said in the February issue of the Journal of Thoracic and Cardiovascular Surgery (2017;153:406-12). They reported on results of all 79 patients with Loeys-Dietz syndrome (LDS) who had cardiovascular surgery at Johns Hopkins. There were two (3%) deaths during surgery and eight (10%) late deaths. Patients with LDS are at risk for dissection early when the aortic root reaches 4 cm. Despite what they termed “favorable” outcomes of surgery, Dr. Patel and his coauthors acknowledged that reintervention rates for this population are high – 19 patients (24%) had subsequent operations. That suggests cardiac surgeons must closely monitor these patients. “Meticulous follow-up with cardiovascular surveillance imaging remains important for management, particularly as clinical LDS subtypes are characterized and more tailored treatment is developed,” Dr. Patel and his coauthors reported.
They advise echocardiography every 3 to 6 months for the first year after surgery and then every 6 to 12 months afterward. Full-body imaging should occur at least every 2 years. “In particular, patients with type B dissections should be monitored aggressively for aneurysm growth,” Dr. Patel and his coauthors said. They recommend imaging at seven to 14 days after dissection, then repeat imaging at 1, 3, 6, and 12 months, and then yearly thereafter.
They noted that four LDS subtypes have been identified. Although those with LDS1 and 2 subtypes are prone to aortic rupture at an earlier age and at smaller aortic diameters than other connective tissue disorders, the medical and surgical management for all subtypes are similar, Dr. Patel and his coauthors indicated.
“Certain congenital heart defects are more common among patients with LDS, compared with the normal population, including patent ductus arteriosus and mitral valve prolapse/insufficiency,” they said. Genotype is one factor that determines the need for surgery in LDS patients, Dr. Patel and his coauthors said. Others are growth rate, aortic valve function, family history, and severity of noncardiac phenotype.
The 79 patients in the study were divided almost evenly between gender, and the average age at first operation was 24.9 years; 38 were children younger than 18 years and 20 had a previous sternotomy. Aortic root replacement represented the predominant operation in the group, accounting for 65 operations (82.3%), of which 52 (80%) were valve-sparing procedures and the remainder were composite valve-graft procedures. The other procedures the researchers performed were nine aortic arch replacements (11.4%), three open thoracoabdominal repairs (3.8%) and two ascending aorta replacements (2.5%).
“Valve-sparing root replacement has become a safe and reliable option for appropriately selected younger patients with LDS,” Dr. Patel and his coauthors wrote. Five patients needed a second operation on the aortic valve or root; three of them had a Florida sleeve procedure. “Based on these initial outcomes with the Florida sleeve at our institution, we have abandoned this procedure in favor of conventional valve-sparing root replacement,” Dr. Patel and his coauthors stated.
Dr. Patel and his coauthors had no financial relationships to disclose.
Key clinical point: Outcomes for aortic surgery in Loeys-Dietz syndrome are favorable, but reintervention rates are high.
Major finding: Patients require close postoperative follow-up with cardiovascular imaging.
Data source: Retrospective review of 79 patients who had cardiovascular surgery for LDS over 26 years at Johns Hopkins University.
VA Secretary Shulkin Calls for Expansion of Health Care to Less Than Honorably Discharged Veterans
Secretary of Veterans Affairs David J. Shulkin, MD, testified before the House Committee on Veterans’ Affairs, promising to tackle the epidemic of suicide and to continue the process to improve the Veterans Choice Act. Dr. Shulkin pledged to begin providing some mental health care service to veterans with other than honorable (OTH) discharges. “We know the rate of death by suicide among veterans who do not use VA care is increasing at a greater rate than veterans who use VA care,” Shulkin told the panel. “This is a national emergency that requires bold action. We must and we will do all that we can to help former service members who may be at risk. When we say even 1 veteran suicide is 1 too many, we mean it.”
Related: Senate, VA Agree—Veterans Choice Act Needs Fixing
The VA estimates that there are more than 500,000 former service members with OTH discharges. Previously, these veterans were not eligible for VA health benefits. As part of the proposal, former OTH service members would be able to seek treatment at a VA emergency department, Vet Center, or Veterans Crisis Line.
“I appreciate Secretary Shulkin taking steps to ensure veterans in crisis with OTH discharges have access to mental health services,” Phil Roe, MD (R-Tenn), chairman of the House Committee on Veterans’ Affairs, said in a written response. “With that said, this must be done in a fair, transparent way that ensures no veteran, especially those who have honorably served, are being skipped over for the care they need. I look forward to continuing this conversation with Secretary Shulkin.”
Related: "Call to Action" on Veteran Suicide Yields Policy Shifts
In addition, Dr. Shulkin revealed that 5.5 million appointments have been made through the Veterans Choice Act and only 5,000 use community care exclusively. The bulk of veterans access both Veterans Choice and VA health care services. The Choice Act is set to expire in less than 6 months on August 7, 2017, if it does not receive congressional reapproval.
To modernize and consolidating the community care portion of the Veterans Choice Act, Shulkin outlined 7 steps:
- High performance integrated network, including VA, other federal health care, and community providers;
- Increase choice for all veterans, starting with those with service-connected health needs;
- Help veterans get care closer to their homes;
- Optimize and coordinate veterans’ care with other insurance providers;
- Maintain affordability for lowest income veterans;
- Assist in care coordination for veterans with multiple care providers; and
- Apply industry standards for quality and affordability to the program.
Secretary of Veterans Affairs David J. Shulkin, MD, testified before the House Committee on Veterans’ Affairs, promising to tackle the epidemic of suicide and to continue the process to improve the Veterans Choice Act. Dr. Shulkin pledged to begin providing some mental health care service to veterans with other than honorable (OTH) discharges. “We know the rate of death by suicide among veterans who do not use VA care is increasing at a greater rate than veterans who use VA care,” Shulkin told the panel. “This is a national emergency that requires bold action. We must and we will do all that we can to help former service members who may be at risk. When we say even 1 veteran suicide is 1 too many, we mean it.”
Related: Senate, VA Agree—Veterans Choice Act Needs Fixing
The VA estimates that there are more than 500,000 former service members with OTH discharges. Previously, these veterans were not eligible for VA health benefits. As part of the proposal, former OTH service members would be able to seek treatment at a VA emergency department, Vet Center, or Veterans Crisis Line.
“I appreciate Secretary Shulkin taking steps to ensure veterans in crisis with OTH discharges have access to mental health services,” Phil Roe, MD (R-Tenn), chairman of the House Committee on Veterans’ Affairs, said in a written response. “With that said, this must be done in a fair, transparent way that ensures no veteran, especially those who have honorably served, are being skipped over for the care they need. I look forward to continuing this conversation with Secretary Shulkin.”
Related: "Call to Action" on Veteran Suicide Yields Policy Shifts
In addition, Dr. Shulkin revealed that 5.5 million appointments have been made through the Veterans Choice Act and only 5,000 use community care exclusively. The bulk of veterans access both Veterans Choice and VA health care services. The Choice Act is set to expire in less than 6 months on August 7, 2017, if it does not receive congressional reapproval.
To modernize and consolidating the community care portion of the Veterans Choice Act, Shulkin outlined 7 steps:
- High performance integrated network, including VA, other federal health care, and community providers;
- Increase choice for all veterans, starting with those with service-connected health needs;
- Help veterans get care closer to their homes;
- Optimize and coordinate veterans’ care with other insurance providers;
- Maintain affordability for lowest income veterans;
- Assist in care coordination for veterans with multiple care providers; and
- Apply industry standards for quality and affordability to the program.
Secretary of Veterans Affairs David J. Shulkin, MD, testified before the House Committee on Veterans’ Affairs, promising to tackle the epidemic of suicide and to continue the process to improve the Veterans Choice Act. Dr. Shulkin pledged to begin providing some mental health care service to veterans with other than honorable (OTH) discharges. “We know the rate of death by suicide among veterans who do not use VA care is increasing at a greater rate than veterans who use VA care,” Shulkin told the panel. “This is a national emergency that requires bold action. We must and we will do all that we can to help former service members who may be at risk. When we say even 1 veteran suicide is 1 too many, we mean it.”
Related: Senate, VA Agree—Veterans Choice Act Needs Fixing
The VA estimates that there are more than 500,000 former service members with OTH discharges. Previously, these veterans were not eligible for VA health benefits. As part of the proposal, former OTH service members would be able to seek treatment at a VA emergency department, Vet Center, or Veterans Crisis Line.
“I appreciate Secretary Shulkin taking steps to ensure veterans in crisis with OTH discharges have access to mental health services,” Phil Roe, MD (R-Tenn), chairman of the House Committee on Veterans’ Affairs, said in a written response. “With that said, this must be done in a fair, transparent way that ensures no veteran, especially those who have honorably served, are being skipped over for the care they need. I look forward to continuing this conversation with Secretary Shulkin.”
Related: "Call to Action" on Veteran Suicide Yields Policy Shifts
In addition, Dr. Shulkin revealed that 5.5 million appointments have been made through the Veterans Choice Act and only 5,000 use community care exclusively. The bulk of veterans access both Veterans Choice and VA health care services. The Choice Act is set to expire in less than 6 months on August 7, 2017, if it does not receive congressional reapproval.
To modernize and consolidating the community care portion of the Veterans Choice Act, Shulkin outlined 7 steps:
- High performance integrated network, including VA, other federal health care, and community providers;
- Increase choice for all veterans, starting with those with service-connected health needs;
- Help veterans get care closer to their homes;
- Optimize and coordinate veterans’ care with other insurance providers;
- Maintain affordability for lowest income veterans;
- Assist in care coordination for veterans with multiple care providers; and
- Apply industry standards for quality and affordability to the program.
When Grief Becomes a Syndrome
Some patients who experience long-term grief may be slipping through the health care net. With data collected in 2 National Institute of Mental Health-funded treatment studies, researchers used proposed criteria from DSM-5 to identify patients with a stress-response syndrome of “persistent impairing grief”—that is, persistent complex bereavement disorder (PCBD), prolonged grief disorder (BGD) and complicated grief (CG). They studied 2 groups of patients in university-based psychiatric research clinics: 240 grief-treatment seeking participants scored ≥ 30 on the Inventory of Complicated Grief (ICG), and 86 bereaved adults scored < 20 on the ICG.
The PCBD criteria diagnosed 70% of the first group, PGD criteria identified 59.6%, and CG criteria identified 99.6%. None of the 3 proposed criteria identified cases in the bereaved comparison group. Only the CG criteria produced rates of case identification sufficient to be of clinical utility, the researchers say.
Their findings are “virtually identical” with those of the community-based National Military Family Bereavement Study, the researchers say, in which all 3 criteria sets identified < 2% of the bereaved military family survey population that scored < 20 on the ICG.
There are treatments specific to grief, the researchers note. But as of yet there is no gold standard for diagnosing persistent impairing grief. The researchers say the solution could lie in using the CG criteria set and modifying decision rules for CBD or PGD criteria or developing a new group of symptoms and decision rules. However it’s done, the researchers conclude, they see a “pressing need” to establish criteria that can lead to correct diagnosis and targeted treatment.
Some patients who experience long-term grief may be slipping through the health care net. With data collected in 2 National Institute of Mental Health-funded treatment studies, researchers used proposed criteria from DSM-5 to identify patients with a stress-response syndrome of “persistent impairing grief”—that is, persistent complex bereavement disorder (PCBD), prolonged grief disorder (BGD) and complicated grief (CG). They studied 2 groups of patients in university-based psychiatric research clinics: 240 grief-treatment seeking participants scored ≥ 30 on the Inventory of Complicated Grief (ICG), and 86 bereaved adults scored < 20 on the ICG.
The PCBD criteria diagnosed 70% of the first group, PGD criteria identified 59.6%, and CG criteria identified 99.6%. None of the 3 proposed criteria identified cases in the bereaved comparison group. Only the CG criteria produced rates of case identification sufficient to be of clinical utility, the researchers say.
Their findings are “virtually identical” with those of the community-based National Military Family Bereavement Study, the researchers say, in which all 3 criteria sets identified < 2% of the bereaved military family survey population that scored < 20 on the ICG.
There are treatments specific to grief, the researchers note. But as of yet there is no gold standard for diagnosing persistent impairing grief. The researchers say the solution could lie in using the CG criteria set and modifying decision rules for CBD or PGD criteria or developing a new group of symptoms and decision rules. However it’s done, the researchers conclude, they see a “pressing need” to establish criteria that can lead to correct diagnosis and targeted treatment.
Some patients who experience long-term grief may be slipping through the health care net. With data collected in 2 National Institute of Mental Health-funded treatment studies, researchers used proposed criteria from DSM-5 to identify patients with a stress-response syndrome of “persistent impairing grief”—that is, persistent complex bereavement disorder (PCBD), prolonged grief disorder (BGD) and complicated grief (CG). They studied 2 groups of patients in university-based psychiatric research clinics: 240 grief-treatment seeking participants scored ≥ 30 on the Inventory of Complicated Grief (ICG), and 86 bereaved adults scored < 20 on the ICG.
The PCBD criteria diagnosed 70% of the first group, PGD criteria identified 59.6%, and CG criteria identified 99.6%. None of the 3 proposed criteria identified cases in the bereaved comparison group. Only the CG criteria produced rates of case identification sufficient to be of clinical utility, the researchers say.
Their findings are “virtually identical” with those of the community-based National Military Family Bereavement Study, the researchers say, in which all 3 criteria sets identified < 2% of the bereaved military family survey population that scored < 20 on the ICG.
There are treatments specific to grief, the researchers note. But as of yet there is no gold standard for diagnosing persistent impairing grief. The researchers say the solution could lie in using the CG criteria set and modifying decision rules for CBD or PGD criteria or developing a new group of symptoms and decision rules. However it’s done, the researchers conclude, they see a “pressing need” to establish criteria that can lead to correct diagnosis and targeted treatment.
Veterans don’t have higher risk of leukemia, lymphoma
People who have served in the Armed Forces do not have an increased risk of leukemia or lymphoma, according to research published in Cancer Epidemiology.
Researchers analyzed the long-term risks of developing leukemia, Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL) in veterans living in Scotland.
At a mean 30 years of follow-up, there were no significant differences in the risk of the aforementioned malignancies between veterans and non-veterans in Scotland.
This retrospective study included 56,205 veterans and 172,741 non-veterans.
The veterans’ earliest date of entering service was January 1960, and the latest date of leaving service was December 2012.
At a mean follow-up of 29.3 years, 294 (0.52%) veterans and 974 (0.56%) non-veterans were diagnosed with leukemia, HL, or NHL.
There were 125 (0.22%) cases of leukemia in veterans and 365 (0.21%) in non-veterans. There were 59 (0.10%) cases of HL in veterans and 182 (0.11%) in non-veterans. And there were 144 (0.26%) cases of NHL in veterans and 538 (0.31%) in non-veterans.
There was no significant difference in the risk of all 3 cancer types between the veterans and non-veterans. The unadjusted hazard ratio (HR) was 0.96 (P=0.541).
There were no significant differences in an adjusted analysis either. (The analysis was adjusted for regional deprivation, which takes into account information on income, employment, health, education, housing, crime, and access to services.)
The adjusted HR was 1.03 (P=0.773) for leukemias, 1.19 (P=0.272) for HL, and 0.86 (P=0.110) for NHL.
“This is an important study which provides reassurance that military service in the last 50 years does not increase people’s risk of leukemia overall,” said study author Beverly Bergman, PhD, of the University of Glasgow in the UK.
“The Armed Forces comply with all relevant health and safety legislation and regulations, and we can now see that their risk is no different from the general population.” 
People who have served in the Armed Forces do not have an increased risk of leukemia or lymphoma, according to research published in Cancer Epidemiology.
Researchers analyzed the long-term risks of developing leukemia, Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL) in veterans living in Scotland.
At a mean 30 years of follow-up, there were no significant differences in the risk of the aforementioned malignancies between veterans and non-veterans in Scotland.
This retrospective study included 56,205 veterans and 172,741 non-veterans.
The veterans’ earliest date of entering service was January 1960, and the latest date of leaving service was December 2012.
At a mean follow-up of 29.3 years, 294 (0.52%) veterans and 974 (0.56%) non-veterans were diagnosed with leukemia, HL, or NHL.
There were 125 (0.22%) cases of leukemia in veterans and 365 (0.21%) in non-veterans. There were 59 (0.10%) cases of HL in veterans and 182 (0.11%) in non-veterans. And there were 144 (0.26%) cases of NHL in veterans and 538 (0.31%) in non-veterans.
There was no significant difference in the risk of all 3 cancer types between the veterans and non-veterans. The unadjusted hazard ratio (HR) was 0.96 (P=0.541).
There were no significant differences in an adjusted analysis either. (The analysis was adjusted for regional deprivation, which takes into account information on income, employment, health, education, housing, crime, and access to services.)
The adjusted HR was 1.03 (P=0.773) for leukemias, 1.19 (P=0.272) for HL, and 0.86 (P=0.110) for NHL.
“This is an important study which provides reassurance that military service in the last 50 years does not increase people’s risk of leukemia overall,” said study author Beverly Bergman, PhD, of the University of Glasgow in the UK.
“The Armed Forces comply with all relevant health and safety legislation and regulations, and we can now see that their risk is no different from the general population.”
People who have served in the Armed Forces do not have an increased risk of leukemia or lymphoma, according to research published in Cancer Epidemiology.
Researchers analyzed the long-term risks of developing leukemia, Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL) in veterans living in Scotland.
At a mean 30 years of follow-up, there were no significant differences in the risk of the aforementioned malignancies between veterans and non-veterans in Scotland.
This retrospective study included 56,205 veterans and 172,741 non-veterans.
The veterans’ earliest date of entering service was January 1960, and the latest date of leaving service was December 2012.
At a mean follow-up of 29.3 years, 294 (0.52%) veterans and 974 (0.56%) non-veterans were diagnosed with leukemia, HL, or NHL.
There were 125 (0.22%) cases of leukemia in veterans and 365 (0.21%) in non-veterans. There were 59 (0.10%) cases of HL in veterans and 182 (0.11%) in non-veterans. And there were 144 (0.26%) cases of NHL in veterans and 538 (0.31%) in non-veterans.
There was no significant difference in the risk of all 3 cancer types between the veterans and non-veterans. The unadjusted hazard ratio (HR) was 0.96 (P=0.541).
There were no significant differences in an adjusted analysis either. (The analysis was adjusted for regional deprivation, which takes into account information on income, employment, health, education, housing, crime, and access to services.)
The adjusted HR was 1.03 (P=0.773) for leukemias, 1.19 (P=0.272) for HL, and 0.86 (P=0.110) for NHL.
“This is an important study which provides reassurance that military service in the last 50 years does not increase people’s risk of leukemia overall,” said study author Beverly Bergman, PhD, of the University of Glasgow in the UK.
“The Armed Forces comply with all relevant health and safety legislation and regulations, and we can now see that their risk is no different from the general population.”
‘Inadequate’ anticoagulation found in AFib patients with stroke
A large study has revealed an association between stroke and “inadequate” anticoagulation among patients with atrial fibrillation.
More than 80% of the patients studied did not receive guideline-recommended anticoagulant therapy prior to having a stroke.
The study also showed that when patients did receive recommended anticoagulants, they had less severe stroke outcomes and a lower risk of death.
These findings were published in JAMA.
“Atrial fibrillation is very common, and people with the condition are at a much higher risk of having stroke,” said study author Ying Xian, MD, PhD, of the Duke University Medical Center in Durham, North Carolina.
“Treatment guidelines call for these patients to receive an anticoagulant such as warfarin at a therapeutic dose or a non-vitamin K antagonist oral anticoagulant (NOAC), so it’s surprising that this is not occurring in the vast majority of cases that occur in community settings.”
The study included 94,474 patients who had an acute ischemic stroke and known history of atrial fibrillation.
The patients were admitted from October 2012 through March 2015 to 1622 hospitals participating in the “Get with the Guidelines-Stroke” program, a national stroke registry sponsored by the American Heart Association and American Stroke Association.
In analyzing data from these patients, the researchers found the following:
- 83.6% of patients were not receiving therapeutic anticoagulation prior to stroke
- 30.3% were not receiving any antithrombotic treatment
- 39.9% were receiving antiplatelet therapy only
- 13.5% were receiving sub-therapeutic warfarin
- 7.6% were receiving therapeutic warfarin
- 8.8% were receiving NOACs.
“While some of these patients may have had reasons for not being anticoagulated, such as high bleeding or fall risk, more than two-thirds had no documented reason for receiving inadequate stroke prevention therapy,” Dr Xian said.
Dr Xian added that, in those cases where anticoagulation failed to prevent a stroke, patients who were on anticoagulant therapy tended to have less severe strokes, with less disability and death.
The researchers said the unadjusted rates of moderate or severe stroke were lower among patients receiving therapeutic warfarin (15.8%) or NOACs (17.5%) than among patients receiving no antithrombotic therapy (27.1%), antiplatelet therapy alone (24.8%), or sub-therapeutic warfarin (25.8%).
The same was true for the unadjusted rates of in-hospital mortality. Patients receiving therapeutic warfarin (6.4%) or NOACs (6.3%) had lower rates than patients receiving no antithrombotic therapy (9.3%), antiplatelet therapy alone (8.1%), or sub-therapeutic warfarin (8.8%).
In an adjusted analysis, the use of therapeutic warfarin, NOACs, or antiplatelet therapy was associated with lower odds of moderate or severe stroke (adjusted odds ratio=0.56, 0.65, and 0.88, respectively) and in-hospital mortality (adjusted odds ratio=0.75, 0.79, and 0.83, respectively), when compared to no antithrombotic treatment.
“These findings highlight the human costs of atrial fibrillation and the importance of appropriate anticoagulation,” Dr Xian said. “Broader adherence to these atrial fibrillation treatment guidelines could substantially reduce both the number and severity of strokes in the US. We estimate that between 58,000 to 88,000 strokes might be preventable per year if the treatment guidelines are followed appropriately.”
A large study has revealed an association between stroke and “inadequate” anticoagulation among patients with atrial fibrillation.
More than 80% of the patients studied did not receive guideline-recommended anticoagulant therapy prior to having a stroke.
The study also showed that when patients did receive recommended anticoagulants, they had less severe stroke outcomes and a lower risk of death.
These findings were published in JAMA.
“Atrial fibrillation is very common, and people with the condition are at a much higher risk of having stroke,” said study author Ying Xian, MD, PhD, of the Duke University Medical Center in Durham, North Carolina.
“Treatment guidelines call for these patients to receive an anticoagulant such as warfarin at a therapeutic dose or a non-vitamin K antagonist oral anticoagulant (NOAC), so it’s surprising that this is not occurring in the vast majority of cases that occur in community settings.”
The study included 94,474 patients who had an acute ischemic stroke and known history of atrial fibrillation.
The patients were admitted from October 2012 through March 2015 to 1622 hospitals participating in the “Get with the Guidelines-Stroke” program, a national stroke registry sponsored by the American Heart Association and American Stroke Association.
In analyzing data from these patients, the researchers found the following:
- 83.6% of patients were not receiving therapeutic anticoagulation prior to stroke
- 30.3% were not receiving any antithrombotic treatment
- 39.9% were receiving antiplatelet therapy only
- 13.5% were receiving sub-therapeutic warfarin
- 7.6% were receiving therapeutic warfarin
- 8.8% were receiving NOACs.
“While some of these patients may have had reasons for not being anticoagulated, such as high bleeding or fall risk, more than two-thirds had no documented reason for receiving inadequate stroke prevention therapy,” Dr Xian said.
Dr Xian added that, in those cases where anticoagulation failed to prevent a stroke, patients who were on anticoagulant therapy tended to have less severe strokes, with less disability and death.
The researchers said the unadjusted rates of moderate or severe stroke were lower among patients receiving therapeutic warfarin (15.8%) or NOACs (17.5%) than among patients receiving no antithrombotic therapy (27.1%), antiplatelet therapy alone (24.8%), or sub-therapeutic warfarin (25.8%).
The same was true for the unadjusted rates of in-hospital mortality. Patients receiving therapeutic warfarin (6.4%) or NOACs (6.3%) had lower rates than patients receiving no antithrombotic therapy (9.3%), antiplatelet therapy alone (8.1%), or sub-therapeutic warfarin (8.8%).
In an adjusted analysis, the use of therapeutic warfarin, NOACs, or antiplatelet therapy was associated with lower odds of moderate or severe stroke (adjusted odds ratio=0.56, 0.65, and 0.88, respectively) and in-hospital mortality (adjusted odds ratio=0.75, 0.79, and 0.83, respectively), when compared to no antithrombotic treatment.
“These findings highlight the human costs of atrial fibrillation and the importance of appropriate anticoagulation,” Dr Xian said. “Broader adherence to these atrial fibrillation treatment guidelines could substantially reduce both the number and severity of strokes in the US. We estimate that between 58,000 to 88,000 strokes might be preventable per year if the treatment guidelines are followed appropriately.”
A large study has revealed an association between stroke and “inadequate” anticoagulation among patients with atrial fibrillation.
More than 80% of the patients studied did not receive guideline-recommended anticoagulant therapy prior to having a stroke.
The study also showed that when patients did receive recommended anticoagulants, they had less severe stroke outcomes and a lower risk of death.
These findings were published in JAMA.
“Atrial fibrillation is very common, and people with the condition are at a much higher risk of having stroke,” said study author Ying Xian, MD, PhD, of the Duke University Medical Center in Durham, North Carolina.
“Treatment guidelines call for these patients to receive an anticoagulant such as warfarin at a therapeutic dose or a non-vitamin K antagonist oral anticoagulant (NOAC), so it’s surprising that this is not occurring in the vast majority of cases that occur in community settings.”
The study included 94,474 patients who had an acute ischemic stroke and known history of atrial fibrillation.
The patients were admitted from October 2012 through March 2015 to 1622 hospitals participating in the “Get with the Guidelines-Stroke” program, a national stroke registry sponsored by the American Heart Association and American Stroke Association.
In analyzing data from these patients, the researchers found the following:
- 83.6% of patients were not receiving therapeutic anticoagulation prior to stroke
- 30.3% were not receiving any antithrombotic treatment
- 39.9% were receiving antiplatelet therapy only
- 13.5% were receiving sub-therapeutic warfarin
- 7.6% were receiving therapeutic warfarin
- 8.8% were receiving NOACs.
“While some of these patients may have had reasons for not being anticoagulated, such as high bleeding or fall risk, more than two-thirds had no documented reason for receiving inadequate stroke prevention therapy,” Dr Xian said.
Dr Xian added that, in those cases where anticoagulation failed to prevent a stroke, patients who were on anticoagulant therapy tended to have less severe strokes, with less disability and death.
The researchers said the unadjusted rates of moderate or severe stroke were lower among patients receiving therapeutic warfarin (15.8%) or NOACs (17.5%) than among patients receiving no antithrombotic therapy (27.1%), antiplatelet therapy alone (24.8%), or sub-therapeutic warfarin (25.8%).
The same was true for the unadjusted rates of in-hospital mortality. Patients receiving therapeutic warfarin (6.4%) or NOACs (6.3%) had lower rates than patients receiving no antithrombotic therapy (9.3%), antiplatelet therapy alone (8.1%), or sub-therapeutic warfarin (8.8%).
In an adjusted analysis, the use of therapeutic warfarin, NOACs, or antiplatelet therapy was associated with lower odds of moderate or severe stroke (adjusted odds ratio=0.56, 0.65, and 0.88, respectively) and in-hospital mortality (adjusted odds ratio=0.75, 0.79, and 0.83, respectively), when compared to no antithrombotic treatment.
“These findings highlight the human costs of atrial fibrillation and the importance of appropriate anticoagulation,” Dr Xian said. “Broader adherence to these atrial fibrillation treatment guidelines could substantially reduce both the number and severity of strokes in the US. We estimate that between 58,000 to 88,000 strokes might be preventable per year if the treatment guidelines are followed appropriately.”
FDA approves pembrolizumab to treat cHL
The US Food and Drug Administration (FDA) has granted accelerated approval for pembrolizumab (Keytruda) as a treatment for adult and pediatric patients with relapsed or refractory classical Hodgkin lymphoma (cHL).
Pembrolizumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the antitumor immune response.
The drug, which is being developed by Merck, previously received FDA approval as a treatment for melanoma, lung cancer, and head and neck cancer.
Now, pembrolizumab has received accelerated approval to treat adult and pediatric patients with refractory cHL or those with cHL who have relapsed after 3 or more prior lines of therapy.
The accelerated approval was based on tumor response rate and durability of response. Continued approval of pembrolizumab for cHL patients may be contingent upon the verification and description of clinical benefit in confirmatory trials.
In adults with cHL, pembrolizumab is administered at a fixed dose of 200 mg every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
In pediatric patients with cHL, pembrolizumab is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
Pembrolizumab trials
The FDA’s approval of pembrolizumab in adults with cHL is based on data from the phase 2 KEYNOTE-087 trial. (The following data were provided by Merck.)
The trial enrolled 210 patients who received pembrolizumab at a dose of 200 mg every 3 weeks until unacceptable toxicity or documented disease progression, or for up to 24 months in patients who did not progress.
Fifty-eight percent of patients were refractory to their last prior therapy, including 35% with primary refractory disease and 14% whose disease was refractory to all prior regimens.
Sixty-one percent of patients had undergone prior autologous hematopoietic stem cell transplant, 83% had prior brentuximab use, and 36% had prior radiation therapy.
At a median follow-up of 9.4 months, the overall response rate was 69%, and the complete response rate was 22%. The median duration of response was 11.1 months (range, 0.0+ to 11.1 months).
Five percent of patients discontinued pembrolizumab due to adverse events (AEs), and 26% had dose interruptions due to AEs. Fifteen percent of patients had an AE requiring systemic corticosteroid therapy.
The most common AEs (occurring in ≥20% of patients) were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).
Serious AEs occurred in 16% of patients. The most frequent serious AEs (≥1%) were pneumonia, pneumonitis, pyrexia, dyspnea, graft-vs-host disease, and herpes zoster.
Two patients died from causes other than disease progression. One death was a result of graft-vs-host disease after subsequent allogeneic transplant, and the other was from septic shock.
There is limited experience with pembrolizumab in pediatric patients. The efficacy of the drug for pediatric patients was extrapolated from the results in the adult cHL population.
However, there is safety data on pembrolizumab in pediatric patients enrolled in the phase 1/2 KEYNOTE-051 trial. (These data were also provided by Merck.)
The trial included 40 pediatric patients with advanced melanoma or PD-L1–positive advanced, relapsed, or refractory solid tumors or lymphoma. Patients in this trial received pembrolizumab for a median of 43 days (range, 1-414 days).
The safety profile in these patients was similar to the profile in adults. Toxicities that occurred at a higher rate (≥15% difference) in pediatric patients than in adults under age 65 were fatigue (45%), vomiting (38%), abdominal pain (28%), hypertransaminasemia (28%), and hyponatremia (18%).
The US Food and Drug Administration (FDA) has granted accelerated approval for pembrolizumab (Keytruda) as a treatment for adult and pediatric patients with relapsed or refractory classical Hodgkin lymphoma (cHL).
Pembrolizumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the antitumor immune response.
The drug, which is being developed by Merck, previously received FDA approval as a treatment for melanoma, lung cancer, and head and neck cancer.
Now, pembrolizumab has received accelerated approval to treat adult and pediatric patients with refractory cHL or those with cHL who have relapsed after 3 or more prior lines of therapy.
The accelerated approval was based on tumor response rate and durability of response. Continued approval of pembrolizumab for cHL patients may be contingent upon the verification and description of clinical benefit in confirmatory trials.
In adults with cHL, pembrolizumab is administered at a fixed dose of 200 mg every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
In pediatric patients with cHL, pembrolizumab is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
Pembrolizumab trials
The FDA’s approval of pembrolizumab in adults with cHL is based on data from the phase 2 KEYNOTE-087 trial. (The following data were provided by Merck.)
The trial enrolled 210 patients who received pembrolizumab at a dose of 200 mg every 3 weeks until unacceptable toxicity or documented disease progression, or for up to 24 months in patients who did not progress.
Fifty-eight percent of patients were refractory to their last prior therapy, including 35% with primary refractory disease and 14% whose disease was refractory to all prior regimens.
Sixty-one percent of patients had undergone prior autologous hematopoietic stem cell transplant, 83% had prior brentuximab use, and 36% had prior radiation therapy.
At a median follow-up of 9.4 months, the overall response rate was 69%, and the complete response rate was 22%. The median duration of response was 11.1 months (range, 0.0+ to 11.1 months).
Five percent of patients discontinued pembrolizumab due to adverse events (AEs), and 26% had dose interruptions due to AEs. Fifteen percent of patients had an AE requiring systemic corticosteroid therapy.
The most common AEs (occurring in ≥20% of patients) were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).
Serious AEs occurred in 16% of patients. The most frequent serious AEs (≥1%) were pneumonia, pneumonitis, pyrexia, dyspnea, graft-vs-host disease, and herpes zoster.
Two patients died from causes other than disease progression. One death was a result of graft-vs-host disease after subsequent allogeneic transplant, and the other was from septic shock.
There is limited experience with pembrolizumab in pediatric patients. The efficacy of the drug for pediatric patients was extrapolated from the results in the adult cHL population.
However, there is safety data on pembrolizumab in pediatric patients enrolled in the phase 1/2 KEYNOTE-051 trial. (These data were also provided by Merck.)
The trial included 40 pediatric patients with advanced melanoma or PD-L1–positive advanced, relapsed, or refractory solid tumors or lymphoma. Patients in this trial received pembrolizumab for a median of 43 days (range, 1-414 days).
The safety profile in these patients was similar to the profile in adults. Toxicities that occurred at a higher rate (≥15% difference) in pediatric patients than in adults under age 65 were fatigue (45%), vomiting (38%), abdominal pain (28%), hypertransaminasemia (28%), and hyponatremia (18%).
The US Food and Drug Administration (FDA) has granted accelerated approval for pembrolizumab (Keytruda) as a treatment for adult and pediatric patients with relapsed or refractory classical Hodgkin lymphoma (cHL).
Pembrolizumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the antitumor immune response.
The drug, which is being developed by Merck, previously received FDA approval as a treatment for melanoma, lung cancer, and head and neck cancer.
Now, pembrolizumab has received accelerated approval to treat adult and pediatric patients with refractory cHL or those with cHL who have relapsed after 3 or more prior lines of therapy.
The accelerated approval was based on tumor response rate and durability of response. Continued approval of pembrolizumab for cHL patients may be contingent upon the verification and description of clinical benefit in confirmatory trials.
In adults with cHL, pembrolizumab is administered at a fixed dose of 200 mg every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
In pediatric patients with cHL, pembrolizumab is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
Pembrolizumab trials
The FDA’s approval of pembrolizumab in adults with cHL is based on data from the phase 2 KEYNOTE-087 trial. (The following data were provided by Merck.)
The trial enrolled 210 patients who received pembrolizumab at a dose of 200 mg every 3 weeks until unacceptable toxicity or documented disease progression, or for up to 24 months in patients who did not progress.
Fifty-eight percent of patients were refractory to their last prior therapy, including 35% with primary refractory disease and 14% whose disease was refractory to all prior regimens.
Sixty-one percent of patients had undergone prior autologous hematopoietic stem cell transplant, 83% had prior brentuximab use, and 36% had prior radiation therapy.
At a median follow-up of 9.4 months, the overall response rate was 69%, and the complete response rate was 22%. The median duration of response was 11.1 months (range, 0.0+ to 11.1 months).
Five percent of patients discontinued pembrolizumab due to adverse events (AEs), and 26% had dose interruptions due to AEs. Fifteen percent of patients had an AE requiring systemic corticosteroid therapy.
The most common AEs (occurring in ≥20% of patients) were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).
Serious AEs occurred in 16% of patients. The most frequent serious AEs (≥1%) were pneumonia, pneumonitis, pyrexia, dyspnea, graft-vs-host disease, and herpes zoster.
Two patients died from causes other than disease progression. One death was a result of graft-vs-host disease after subsequent allogeneic transplant, and the other was from septic shock.
There is limited experience with pembrolizumab in pediatric patients. The efficacy of the drug for pediatric patients was extrapolated from the results in the adult cHL population.
However, there is safety data on pembrolizumab in pediatric patients enrolled in the phase 1/2 KEYNOTE-051 trial. (These data were also provided by Merck.)
The trial included 40 pediatric patients with advanced melanoma or PD-L1–positive advanced, relapsed, or refractory solid tumors or lymphoma. Patients in this trial received pembrolizumab for a median of 43 days (range, 1-414 days).
The safety profile in these patients was similar to the profile in adults. Toxicities that occurred at a higher rate (≥15% difference) in pediatric patients than in adults under age 65 were fatigue (45%), vomiting (38%), abdominal pain (28%), hypertransaminasemia (28%), and hyponatremia (18%).
HDAC6 inhibitors reverse CIPN in rodents
Histone deacetylase (HDAC) inhibitors can treat chemotherapy-induced peripheral neuropathy (CIPN) in mice and rats, according to research published in PAIN.
The animals developed CIPN after treatment with cisplatin or paclitaxel.
But treatment with an HDAC6 inhibitor—ACY-1083 or ricolinostat (ACY-1215)—was able to reverse and sometimes prevent the symptoms of CIPN in the animals.
The researchers said these findings are “especially promising” because one of the HDAC6 inhibitors, ricolinostat, is already being tested in clinical trials.
This research was funded, in part, by Acetylon Pharmaceuticals Inc., and employees of the company were involved in the research.
The HDAC6 inhibitors are being developed by Regenacy Pharmaceuticals, LLC, a spinout of Acetylon Pharmaceuticals.
The researchers found that ACY-1083 was able to reverse cisplatin-induced mechanical allodynia (pain in response to touch) in mice.
ACY-1083 also prevented mechanical allodynia when given an hour prior to treatment with cisplatin.
The team noted that ricolinostat, which is less selective for HDAC6 than ACY-1083, also reversed cisplatin-induced mechanical allodynia.
The beneficial effect of ricolinostat was still seen a week after treatment, which was the last time point tested.
The researchers also found that ACY-1083 was able to reverse paclitaxel-induced mechanical allodynia in rats.
And ACY-1083 could reverse cisplatin-induced spontaneous pain and numbness in mice.
“These data demonstrate that HDAC6 is a novel therapeutic target for the treatment of chemotherapy-induced neuropathies, for which there are currently no FDA-approved drugs,” said Matthew B. Jarpe, PhD, associate vice-president of biology at Regenacy Pharmaceuticals.
Dr Jarpe said this research suggests an HDAC6 inhibitor could potentially be used in conjunction with platinum- or taxane-based chemotherapy to allow for higher and/or longer chemotherapy dosing regimens.
“Additionally, the reversal of both pain and numbness in this preclinical model suggests that an HDAC6 inhibitor could be used after a course of chemotherapy is completed to treat and potentially reverse resultant debilitating CIPN symptoms that impact function and quality of life for many patients,” he said.
“Preclinical results seen with the clinical candidate ricolinostat highlight the translational potential of these findings to the clinic.”
Histone deacetylase (HDAC) inhibitors can treat chemotherapy-induced peripheral neuropathy (CIPN) in mice and rats, according to research published in PAIN.
The animals developed CIPN after treatment with cisplatin or paclitaxel.
But treatment with an HDAC6 inhibitor—ACY-1083 or ricolinostat (ACY-1215)—was able to reverse and sometimes prevent the symptoms of CIPN in the animals.
The researchers said these findings are “especially promising” because one of the HDAC6 inhibitors, ricolinostat, is already being tested in clinical trials.
This research was funded, in part, by Acetylon Pharmaceuticals Inc., and employees of the company were involved in the research.
The HDAC6 inhibitors are being developed by Regenacy Pharmaceuticals, LLC, a spinout of Acetylon Pharmaceuticals.
The researchers found that ACY-1083 was able to reverse cisplatin-induced mechanical allodynia (pain in response to touch) in mice.
ACY-1083 also prevented mechanical allodynia when given an hour prior to treatment with cisplatin.
The team noted that ricolinostat, which is less selective for HDAC6 than ACY-1083, also reversed cisplatin-induced mechanical allodynia.
The beneficial effect of ricolinostat was still seen a week after treatment, which was the last time point tested.
The researchers also found that ACY-1083 was able to reverse paclitaxel-induced mechanical allodynia in rats.
And ACY-1083 could reverse cisplatin-induced spontaneous pain and numbness in mice.
“These data demonstrate that HDAC6 is a novel therapeutic target for the treatment of chemotherapy-induced neuropathies, for which there are currently no FDA-approved drugs,” said Matthew B. Jarpe, PhD, associate vice-president of biology at Regenacy Pharmaceuticals.
Dr Jarpe said this research suggests an HDAC6 inhibitor could potentially be used in conjunction with platinum- or taxane-based chemotherapy to allow for higher and/or longer chemotherapy dosing regimens.
“Additionally, the reversal of both pain and numbness in this preclinical model suggests that an HDAC6 inhibitor could be used after a course of chemotherapy is completed to treat and potentially reverse resultant debilitating CIPN symptoms that impact function and quality of life for many patients,” he said.
“Preclinical results seen with the clinical candidate ricolinostat highlight the translational potential of these findings to the clinic.”
Histone deacetylase (HDAC) inhibitors can treat chemotherapy-induced peripheral neuropathy (CIPN) in mice and rats, according to research published in PAIN.
The animals developed CIPN after treatment with cisplatin or paclitaxel.
But treatment with an HDAC6 inhibitor—ACY-1083 or ricolinostat (ACY-1215)—was able to reverse and sometimes prevent the symptoms of CIPN in the animals.
The researchers said these findings are “especially promising” because one of the HDAC6 inhibitors, ricolinostat, is already being tested in clinical trials.
This research was funded, in part, by Acetylon Pharmaceuticals Inc., and employees of the company were involved in the research.
The HDAC6 inhibitors are being developed by Regenacy Pharmaceuticals, LLC, a spinout of Acetylon Pharmaceuticals.
The researchers found that ACY-1083 was able to reverse cisplatin-induced mechanical allodynia (pain in response to touch) in mice.
ACY-1083 also prevented mechanical allodynia when given an hour prior to treatment with cisplatin.
The team noted that ricolinostat, which is less selective for HDAC6 than ACY-1083, also reversed cisplatin-induced mechanical allodynia.
The beneficial effect of ricolinostat was still seen a week after treatment, which was the last time point tested.
The researchers also found that ACY-1083 was able to reverse paclitaxel-induced mechanical allodynia in rats.
And ACY-1083 could reverse cisplatin-induced spontaneous pain and numbness in mice.
“These data demonstrate that HDAC6 is a novel therapeutic target for the treatment of chemotherapy-induced neuropathies, for which there are currently no FDA-approved drugs,” said Matthew B. Jarpe, PhD, associate vice-president of biology at Regenacy Pharmaceuticals.
Dr Jarpe said this research suggests an HDAC6 inhibitor could potentially be used in conjunction with platinum- or taxane-based chemotherapy to allow for higher and/or longer chemotherapy dosing regimens.
“Additionally, the reversal of both pain and numbness in this preclinical model suggests that an HDAC6 inhibitor could be used after a course of chemotherapy is completed to treat and potentially reverse resultant debilitating CIPN symptoms that impact function and quality of life for many patients,” he said.
“Preclinical results seen with the clinical candidate ricolinostat highlight the translational potential of these findings to the clinic.”
Steroids During Late Preterm Labor? Better Later Than Never
A 21-year-old G1P0 at 35 weeks, 2 days of gestation presents to labor and delivery reporting a “gush of clear fluid.” On exam, you confirm she has preterm rupture of membranes. She is contracting every three minutes and has a cervix dilated to 3 cm. Is there any neonatal benefit to using corticosteroids in this late preterm period?
Approximately 12% of all births in the United States are the result of preterm labor, and 8% take place in the late preterm period, defined as 34 to 36 weeks’ gestation.2,3 To reduce risk for neonatal death and respiratory complications, both the American College of Obstetricians and Gynecologists and the National Institutes of Health recommend a course of corticosteroids between 24 and 34 weeks’ gestation for women at increased risk for preterm delivery.2,4 Due to a lack of evidence from RCTs on the benefit of corticosteroids in late preterm labor, there are no recommendations to extend this period.5 However, multiple studies have shown that babies born during the late preterm period have more neonatal complications than term newborns.6-8
A retrospective chart review of more than 130,000 live births found that newborns who were delivered between 34 and 36 weeks had higher rates of respiratory distress than those delivered at 39 weeks (ventilator use dropped from 3.3% at 34 weeks to 0.3% at 39 weeks, and transient tachypnea decreased from 2.4% at 34 weeks to 0.4% at 39 weeks).6 Another retrospective review of more than 230,000 newborns, 19,000 of whom were born in the late preterm period, revealed that more neonates born between 34 and 36 weeks’ gestation had respiratory distress syndrome than neonates delivered at 39 weeks (10.5% at 34 weeks, 6% at 35 weeks, 2.8% at 36 weeks vs 0.3% at 39 weeks).8
STUDY SUMMARY
Late preterm newborns breathe better with antenatal betamethasone
This RCT examined the effectiveness of betamethasone in preventing neonatal respiratory complications for 2,831 women at high probability of preterm delivery between 34 weeks and 36 weeks, 6 days of gestation. “High probability of preterm delivery” was defined as preterm labor with intact membranes and at least 3 cm dilation or 75% cervical effacement; spontaneous rupture of membranes; or anticipated preterm delivery for any other indication either through induction or cesarean section between 24 hours and seven days after the planned randomization.
Patients were randomly assigned to receive two intramuscular injections (12 mg each) of either betamethasone or placebo, 24 hours apart. The two doses were successfully given in 60% of the betamethasone group and 59% of the placebo group. In 95% of the cases in which the second dose was not given, it was because delivery occurred within 24 hours of the first dose.
The primary outcome was the need for respiratory support within 72 hours of birth, defined as one or more of the following: the use of continuous positive airway pressure (CPAP) or high-flow nasal cannula for at least two consecutive hours, supplemental oxygen for at least four continuous hours, extracorporeal membrane oxygenation (ECMO), or mechanical ventilation.
The median length of time from enrollment to delivery was 31 to 33 hours, and 31.4% underwent cesarean delivery. In the intention-to-treat analysis, the primary outcome was significantly lower in the betamethasone group than in the placebo group (11.6% vs 14.4%; relative risk [RR], 0.80; number needed to treat [NNT], 35). Secondary outcomes (severe complications, representing a composite of the use of CPAP or high-flow nasal cannula for at least 12 continuous hours, supplemental oxygen for at least 24 continuous hours, ECMO, mechanical ventilation, stillbirth, or neonatal death within 72 hours after delivery) were also lower in the betamethasone group (8.1% vs 12.1%; RR, 0.67; NNT, 25). The betamethasone group also had a lower risk for transient tachypnea of the newborn (6.7% vs 9.9%; RR, 0.68).
There were no significant differences in the occurrence of maternal chorioamnionitis or endometritis between the groups. Hypoglycemia in the newborn occurred more in the betamethasone group (24% vs 15%; RR, 1.6; number needed to harm [NNH], 11). The betamethasone group had two neonatal deaths: one from septic shock, and the other from a structural cardiac anomaly and arrhythmia.
WHAT’S NEW
Betamethasone effective even in the late, late preterm period
This study demonstrated an improvement in neonatal respiratory outcomes when betamethasone versus placebo was used in the late preterm period. The findings were similar to those from the Antenatal Steroids for Term Elective Caesarean Section Research Team.9 Their trial showed a reduction in respiratory complications in term neonates delivered via elective cesarean section to mothers who received antenatal betamethasone (NNT, 37, to prevent admission to a special care nursery with respiratory distress). The findings were also consistent with those of a recent meta-analysis evaluating the occurrence of respiratory complications with the use of antenatal betamethasone in women expected to deliver in the late preterm period or with a planned cesarean delivery at ≥ 37 weeks’ gestation.10
CAVEATS
Neonates may develop hypoglycemia
The authors of the study reported an increased risk for hypoglycemia in the neonates receiving antenatal betamethasone. The long-term implications of this are unclear, however, given that there was a reduction in intermediate care nursery and neonatal ICU stays that were three days or longer in the betamethasone group. There was also no difference in hospital length of stay between the two groups. Additionally, it’s unclear if there are any long-term neonatal complications of betamethasone use in the late preterm period.
CHALLENGES TO IMPLEMENTATION
Challenges are negligible
There are minimal challenges to implementing this strategy, as betamethasone is routinely used for preterm labor and is readily available on labor and delivery units.
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.
Copyright © 2017. The Family Physicians Inquiries Network. All rights reserved.
Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2017;66(2):104-106.
1. Gyamfi-Bannerman C, Thom EA, Blackwell SC, et al; NICHD Maternal–Fetal Medicine Units Network. Antenatal betamethasone for women at risk for late preterm delivery. N Engl J Med. 2016;374:1311-1320.
2. Practice Bulletin No. 159 Summary: Management of Preterm Labor. Obstet Gynecol. 2016;127:190-191.
3. Martin JA, Hamilton BE, Osterman MJ, et al. Births: final data for 2013. Natl Vital Stat Rep. 2015;64:1-65.
4. Effect of corticosteroids for fetal maturation on perinatal outcomes. NIH Consens Statement. 1994;12:1-24.
5. Society for Maternal-Fetal Medicine (SMFM) Publications Committee. Implementation of the use of antenatal corticosteroids in the late preterm birth period in women at risk for preterm delivery. Am J Obstet Gynecol. 2016;215:B13-B15.
6. McIntire DD, Leveno KJ. Neonatal mortality and morbidity rates in late preterm births compared with births at term. Obstet Gynecol. 2008;111:35-41.
7. Yoder BA, Gordon MC, Barth WH Jr. Late-preterm birth: does the changing obstetric paradigm alter the epidemiology of respiratory complications? Obstet Gynecol. 2008;111:814-822.
8. Consortium on Safe Labor, Hibbard JU, Wilkins I, Sun L, et al. Respiratory morbidity in late preterm births. JAMA. 2010;304:419-425.
9. Stutchfield P, Whitaker R, Russell I. Antenatal betamethasone and incidence of neonatal respiratory distress after elective caesarean section: pragmatic randomised trial. BMJ. 2005;331:662.
10. Saccone G, Berghella V. Antenatal corticosteroids for maturity of term or near term fetuses: systematic review and meta-analysis of randomized controlled trials. BMJ. 2016;355:i5044.
A 21-year-old G1P0 at 35 weeks, 2 days of gestation presents to labor and delivery reporting a “gush of clear fluid.” On exam, you confirm she has preterm rupture of membranes. She is contracting every three minutes and has a cervix dilated to 3 cm. Is there any neonatal benefit to using corticosteroids in this late preterm period?
Approximately 12% of all births in the United States are the result of preterm labor, and 8% take place in the late preterm period, defined as 34 to 36 weeks’ gestation.2,3 To reduce risk for neonatal death and respiratory complications, both the American College of Obstetricians and Gynecologists and the National Institutes of Health recommend a course of corticosteroids between 24 and 34 weeks’ gestation for women at increased risk for preterm delivery.2,4 Due to a lack of evidence from RCTs on the benefit of corticosteroids in late preterm labor, there are no recommendations to extend this period.5 However, multiple studies have shown that babies born during the late preterm period have more neonatal complications than term newborns.6-8
A retrospective chart review of more than 130,000 live births found that newborns who were delivered between 34 and 36 weeks had higher rates of respiratory distress than those delivered at 39 weeks (ventilator use dropped from 3.3% at 34 weeks to 0.3% at 39 weeks, and transient tachypnea decreased from 2.4% at 34 weeks to 0.4% at 39 weeks).6 Another retrospective review of more than 230,000 newborns, 19,000 of whom were born in the late preterm period, revealed that more neonates born between 34 and 36 weeks’ gestation had respiratory distress syndrome than neonates delivered at 39 weeks (10.5% at 34 weeks, 6% at 35 weeks, 2.8% at 36 weeks vs 0.3% at 39 weeks).8
STUDY SUMMARY
Late preterm newborns breathe better with antenatal betamethasone
This RCT examined the effectiveness of betamethasone in preventing neonatal respiratory complications for 2,831 women at high probability of preterm delivery between 34 weeks and 36 weeks, 6 days of gestation. “High probability of preterm delivery” was defined as preterm labor with intact membranes and at least 3 cm dilation or 75% cervical effacement; spontaneous rupture of membranes; or anticipated preterm delivery for any other indication either through induction or cesarean section between 24 hours and seven days after the planned randomization.
Patients were randomly assigned to receive two intramuscular injections (12 mg each) of either betamethasone or placebo, 24 hours apart. The two doses were successfully given in 60% of the betamethasone group and 59% of the placebo group. In 95% of the cases in which the second dose was not given, it was because delivery occurred within 24 hours of the first dose.
The primary outcome was the need for respiratory support within 72 hours of birth, defined as one or more of the following: the use of continuous positive airway pressure (CPAP) or high-flow nasal cannula for at least two consecutive hours, supplemental oxygen for at least four continuous hours, extracorporeal membrane oxygenation (ECMO), or mechanical ventilation.
The median length of time from enrollment to delivery was 31 to 33 hours, and 31.4% underwent cesarean delivery. In the intention-to-treat analysis, the primary outcome was significantly lower in the betamethasone group than in the placebo group (11.6% vs 14.4%; relative risk [RR], 0.80; number needed to treat [NNT], 35). Secondary outcomes (severe complications, representing a composite of the use of CPAP or high-flow nasal cannula for at least 12 continuous hours, supplemental oxygen for at least 24 continuous hours, ECMO, mechanical ventilation, stillbirth, or neonatal death within 72 hours after delivery) were also lower in the betamethasone group (8.1% vs 12.1%; RR, 0.67; NNT, 25). The betamethasone group also had a lower risk for transient tachypnea of the newborn (6.7% vs 9.9%; RR, 0.68).
There were no significant differences in the occurrence of maternal chorioamnionitis or endometritis between the groups. Hypoglycemia in the newborn occurred more in the betamethasone group (24% vs 15%; RR, 1.6; number needed to harm [NNH], 11). The betamethasone group had two neonatal deaths: one from septic shock, and the other from a structural cardiac anomaly and arrhythmia.
WHAT’S NEW
Betamethasone effective even in the late, late preterm period
This study demonstrated an improvement in neonatal respiratory outcomes when betamethasone versus placebo was used in the late preterm period. The findings were similar to those from the Antenatal Steroids for Term Elective Caesarean Section Research Team.9 Their trial showed a reduction in respiratory complications in term neonates delivered via elective cesarean section to mothers who received antenatal betamethasone (NNT, 37, to prevent admission to a special care nursery with respiratory distress). The findings were also consistent with those of a recent meta-analysis evaluating the occurrence of respiratory complications with the use of antenatal betamethasone in women expected to deliver in the late preterm period or with a planned cesarean delivery at ≥ 37 weeks’ gestation.10
CAVEATS
Neonates may develop hypoglycemia
The authors of the study reported an increased risk for hypoglycemia in the neonates receiving antenatal betamethasone. The long-term implications of this are unclear, however, given that there was a reduction in intermediate care nursery and neonatal ICU stays that were three days or longer in the betamethasone group. There was also no difference in hospital length of stay between the two groups. Additionally, it’s unclear if there are any long-term neonatal complications of betamethasone use in the late preterm period.
CHALLENGES TO IMPLEMENTATION
Challenges are negligible
There are minimal challenges to implementing this strategy, as betamethasone is routinely used for preterm labor and is readily available on labor and delivery units.
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.
Copyright © 2017. The Family Physicians Inquiries Network. All rights reserved.
Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2017;66(2):104-106.
A 21-year-old G1P0 at 35 weeks, 2 days of gestation presents to labor and delivery reporting a “gush of clear fluid.” On exam, you confirm she has preterm rupture of membranes. She is contracting every three minutes and has a cervix dilated to 3 cm. Is there any neonatal benefit to using corticosteroids in this late preterm period?
Approximately 12% of all births in the United States are the result of preterm labor, and 8% take place in the late preterm period, defined as 34 to 36 weeks’ gestation.2,3 To reduce risk for neonatal death and respiratory complications, both the American College of Obstetricians and Gynecologists and the National Institutes of Health recommend a course of corticosteroids between 24 and 34 weeks’ gestation for women at increased risk for preterm delivery.2,4 Due to a lack of evidence from RCTs on the benefit of corticosteroids in late preterm labor, there are no recommendations to extend this period.5 However, multiple studies have shown that babies born during the late preterm period have more neonatal complications than term newborns.6-8
A retrospective chart review of more than 130,000 live births found that newborns who were delivered between 34 and 36 weeks had higher rates of respiratory distress than those delivered at 39 weeks (ventilator use dropped from 3.3% at 34 weeks to 0.3% at 39 weeks, and transient tachypnea decreased from 2.4% at 34 weeks to 0.4% at 39 weeks).6 Another retrospective review of more than 230,000 newborns, 19,000 of whom were born in the late preterm period, revealed that more neonates born between 34 and 36 weeks’ gestation had respiratory distress syndrome than neonates delivered at 39 weeks (10.5% at 34 weeks, 6% at 35 weeks, 2.8% at 36 weeks vs 0.3% at 39 weeks).8
STUDY SUMMARY
Late preterm newborns breathe better with antenatal betamethasone
This RCT examined the effectiveness of betamethasone in preventing neonatal respiratory complications for 2,831 women at high probability of preterm delivery between 34 weeks and 36 weeks, 6 days of gestation. “High probability of preterm delivery” was defined as preterm labor with intact membranes and at least 3 cm dilation or 75% cervical effacement; spontaneous rupture of membranes; or anticipated preterm delivery for any other indication either through induction or cesarean section between 24 hours and seven days after the planned randomization.
Patients were randomly assigned to receive two intramuscular injections (12 mg each) of either betamethasone or placebo, 24 hours apart. The two doses were successfully given in 60% of the betamethasone group and 59% of the placebo group. In 95% of the cases in which the second dose was not given, it was because delivery occurred within 24 hours of the first dose.
The primary outcome was the need for respiratory support within 72 hours of birth, defined as one or more of the following: the use of continuous positive airway pressure (CPAP) or high-flow nasal cannula for at least two consecutive hours, supplemental oxygen for at least four continuous hours, extracorporeal membrane oxygenation (ECMO), or mechanical ventilation.
The median length of time from enrollment to delivery was 31 to 33 hours, and 31.4% underwent cesarean delivery. In the intention-to-treat analysis, the primary outcome was significantly lower in the betamethasone group than in the placebo group (11.6% vs 14.4%; relative risk [RR], 0.80; number needed to treat [NNT], 35). Secondary outcomes (severe complications, representing a composite of the use of CPAP or high-flow nasal cannula for at least 12 continuous hours, supplemental oxygen for at least 24 continuous hours, ECMO, mechanical ventilation, stillbirth, or neonatal death within 72 hours after delivery) were also lower in the betamethasone group (8.1% vs 12.1%; RR, 0.67; NNT, 25). The betamethasone group also had a lower risk for transient tachypnea of the newborn (6.7% vs 9.9%; RR, 0.68).
There were no significant differences in the occurrence of maternal chorioamnionitis or endometritis between the groups. Hypoglycemia in the newborn occurred more in the betamethasone group (24% vs 15%; RR, 1.6; number needed to harm [NNH], 11). The betamethasone group had two neonatal deaths: one from septic shock, and the other from a structural cardiac anomaly and arrhythmia.
WHAT’S NEW
Betamethasone effective even in the late, late preterm period
This study demonstrated an improvement in neonatal respiratory outcomes when betamethasone versus placebo was used in the late preterm period. The findings were similar to those from the Antenatal Steroids for Term Elective Caesarean Section Research Team.9 Their trial showed a reduction in respiratory complications in term neonates delivered via elective cesarean section to mothers who received antenatal betamethasone (NNT, 37, to prevent admission to a special care nursery with respiratory distress). The findings were also consistent with those of a recent meta-analysis evaluating the occurrence of respiratory complications with the use of antenatal betamethasone in women expected to deliver in the late preterm period or with a planned cesarean delivery at ≥ 37 weeks’ gestation.10
CAVEATS
Neonates may develop hypoglycemia
The authors of the study reported an increased risk for hypoglycemia in the neonates receiving antenatal betamethasone. The long-term implications of this are unclear, however, given that there was a reduction in intermediate care nursery and neonatal ICU stays that were three days or longer in the betamethasone group. There was also no difference in hospital length of stay between the two groups. Additionally, it’s unclear if there are any long-term neonatal complications of betamethasone use in the late preterm period.
CHALLENGES TO IMPLEMENTATION
Challenges are negligible
There are minimal challenges to implementing this strategy, as betamethasone is routinely used for preterm labor and is readily available on labor and delivery units.
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.
Copyright © 2017. The Family Physicians Inquiries Network. All rights reserved.
Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2017;66(2):104-106.
1. Gyamfi-Bannerman C, Thom EA, Blackwell SC, et al; NICHD Maternal–Fetal Medicine Units Network. Antenatal betamethasone for women at risk for late preterm delivery. N Engl J Med. 2016;374:1311-1320.
2. Practice Bulletin No. 159 Summary: Management of Preterm Labor. Obstet Gynecol. 2016;127:190-191.
3. Martin JA, Hamilton BE, Osterman MJ, et al. Births: final data for 2013. Natl Vital Stat Rep. 2015;64:1-65.
4. Effect of corticosteroids for fetal maturation on perinatal outcomes. NIH Consens Statement. 1994;12:1-24.
5. Society for Maternal-Fetal Medicine (SMFM) Publications Committee. Implementation of the use of antenatal corticosteroids in the late preterm birth period in women at risk for preterm delivery. Am J Obstet Gynecol. 2016;215:B13-B15.
6. McIntire DD, Leveno KJ. Neonatal mortality and morbidity rates in late preterm births compared with births at term. Obstet Gynecol. 2008;111:35-41.
7. Yoder BA, Gordon MC, Barth WH Jr. Late-preterm birth: does the changing obstetric paradigm alter the epidemiology of respiratory complications? Obstet Gynecol. 2008;111:814-822.
8. Consortium on Safe Labor, Hibbard JU, Wilkins I, Sun L, et al. Respiratory morbidity in late preterm births. JAMA. 2010;304:419-425.
9. Stutchfield P, Whitaker R, Russell I. Antenatal betamethasone and incidence of neonatal respiratory distress after elective caesarean section: pragmatic randomised trial. BMJ. 2005;331:662.
10. Saccone G, Berghella V. Antenatal corticosteroids for maturity of term or near term fetuses: systematic review and meta-analysis of randomized controlled trials. BMJ. 2016;355:i5044.
1. Gyamfi-Bannerman C, Thom EA, Blackwell SC, et al; NICHD Maternal–Fetal Medicine Units Network. Antenatal betamethasone for women at risk for late preterm delivery. N Engl J Med. 2016;374:1311-1320.
2. Practice Bulletin No. 159 Summary: Management of Preterm Labor. Obstet Gynecol. 2016;127:190-191.
3. Martin JA, Hamilton BE, Osterman MJ, et al. Births: final data for 2013. Natl Vital Stat Rep. 2015;64:1-65.
4. Effect of corticosteroids for fetal maturation on perinatal outcomes. NIH Consens Statement. 1994;12:1-24.
5. Society for Maternal-Fetal Medicine (SMFM) Publications Committee. Implementation of the use of antenatal corticosteroids in the late preterm birth period in women at risk for preterm delivery. Am J Obstet Gynecol. 2016;215:B13-B15.
6. McIntire DD, Leveno KJ. Neonatal mortality and morbidity rates in late preterm births compared with births at term. Obstet Gynecol. 2008;111:35-41.
7. Yoder BA, Gordon MC, Barth WH Jr. Late-preterm birth: does the changing obstetric paradigm alter the epidemiology of respiratory complications? Obstet Gynecol. 2008;111:814-822.
8. Consortium on Safe Labor, Hibbard JU, Wilkins I, Sun L, et al. Respiratory morbidity in late preterm births. JAMA. 2010;304:419-425.
9. Stutchfield P, Whitaker R, Russell I. Antenatal betamethasone and incidence of neonatal respiratory distress after elective caesarean section: pragmatic randomised trial. BMJ. 2005;331:662.
10. Saccone G, Berghella V. Antenatal corticosteroids for maturity of term or near term fetuses: systematic review and meta-analysis of randomized controlled trials. BMJ. 2016;355:i5044.
SPECIAL REPORT: SVS Takes Aim at Addressing Physician Burnout, Wellness
In my editorial in the November issue of Vascular Specialist I asked the question: Are we ok? I received many responses from members and I think the collective answer is best characterized as …maybe. Like nearly every other physician, I have witnessed the effects of burnout for my entire career. After high school, I enrolled in a BA/MD program with about 60 other students. Nearly half never matriculated. After medical school, I began a general surgery residency with seven other categorical interns. Six of them quit in the first year. What we now call burnout was once thought of as a process for weeding out those who could not “hack” it. Those students were not fit to be doctors; those interns were not fit to be surgeons. The process worked. Or so we thought.
The epidemic of physician burnout has raised alarm in many healthcare organizations. This mental state, characterized by emotional exhaustion, depersonalization and a diminished sense of personal accomplishment, has adverse consequences for both patient and clinician. The statistics are sobering. More than half of physicians, by self-report, have symptoms of burnout. No clinician is immune. Significant numbers of nurses and residents are similarly affected. The trend is worrisome. Compared to 2011, the percentage of physicians with burnout symptoms has increased, and the percentage satisfied with their work/life balance has decreased. Burnout affects physicians across all specialties, but the picture is particularly grim for surgeons, and even a bit more so for vascular surgeons. Compared with 13 other surgical specialties, vascular surgeons report the second highest rate of burnout. They also report the lowest level of career satisfaction, ranked first in stating they may have chosen an alternate career if they could choose again, and first in recommending an alternate career to medicine to their children.
In light of these sobering data, it must become an increasing concern of SVS as our professional home, as well as APDVS, as the professional home for Program Directors in Vascular Surgery, when almost a third of vascular surgeons report depression, and when compared to other surgical specialties, the highest incidence of suicidal ideation occurs in our own colleagues. Perhaps most importantly, 70 percent of physicians who score in the lower third on the Physician Well-Being Index report their well-being as average or above average. So relying on introspection offers limited hope.
Burnout is also a patient care-quality issue. Patients who are cared for by clinicians suffering from burnout do not fare well. A burned-out physician may appear to colleagues as frustrated, cynical and even callous, and to his or her patients as lacking empathy and compassion. Only 53 percent of patients, when surveyed, believe the health care system provides compassionate care. Diabetic patients of physicians with high empathy scores had improved control of HbA1c, fewer hospitalizations and fewer serious complications. Similarly, those with cancer had improved psychological adjustment, decreased ICU utilization and an improved immune response.
What does this landscape look like to those starting their medical careers – our future vascular surgeons? As a rule, students enter medical school altruistic and idealistic, excited about becoming a doctor, empathic and eager to care for their future patients. What follows is a decline in compassion, a crucial ingredient to mitigate burnout. Their curriculum focuses on emotional detachment and affective distancing for the purpose of clinical neutrality. Twenty percent of medical school graduates reported that they experienced disconnects between what they were taught about professional behaviors and attitudes and what they saw demonstrated by their faculty. Empathy is further eroded as residents experience “time-constrained” patient interactions in the clinic, the emergency department and the operating room. They often work with frustrated and overwhelmed faculty members who are experiencing increased pressure to generate greater clinical revenue and struggle with non-intuitive electronic medical record systems.
By almost any metric, vascular surgeons’ work is stressful. They work long hours, spend considerable hours in the operating room (average 20 hours a week) and average 2.7 nights of call a week. The vascular surgery workforce needs to continue to increase in light of the aging population that generally is sicker, yet demanding of more active lives. The demand will not be met without improving the health of our workforce.
Burnout also leads to early retirement. And burnout predicts the future. Each one-point change on the emotional exhaustion burnout scale is associated with a 43 percent higher likelihood that the affected physicians will reduce their FTE over the ensuing 24 months. Compounding supply further are the issues at the front end. An alarming 69 percent of U.S. general surgery trainees meet the criteria for burnout, and 44 percent of the 753 general surgery residents sampled considered dropping out of their training program; an even greater proportion considered doing so if they had symptoms of burnout. Women in training were at a higher risk of burnout compared to men. Although a study of burnout and job satisfaction in members of the American College of Surgeons found that private-practice surgeons were more likely to experience burnout than surgeons practicing in academic settings, Elmore et. al. observed that residents who planned to enter private practice reported higher levels of burnout.
In summary, burnout out is real and is impacting the health, well-being, and careers of vascular surgeons. Burnout places both the surgeon and the patient at risk for a poor outcome. Burnout influences medical student and resident career choices. Burnout can no longer be ignored – doing nothing is not an option.
Can the Society of Vascular Surgery do anything to improve the well-being of its members? We will begin that discussion next month.
*The authors extend their thanks and appreciation for the guidance, resources and support of Michael Goldberg, M.D., Scholar in Residence, Schwartz Center for Compassionate Care, Boston, Mass., and Clinical Professor of Orthopedics at Seattle Children’s Hospital..
In my editorial in the November issue of Vascular Specialist I asked the question: Are we ok? I received many responses from members and I think the collective answer is best characterized as …maybe. Like nearly every other physician, I have witnessed the effects of burnout for my entire career. After high school, I enrolled in a BA/MD program with about 60 other students. Nearly half never matriculated. After medical school, I began a general surgery residency with seven other categorical interns. Six of them quit in the first year. What we now call burnout was once thought of as a process for weeding out those who could not “hack” it. Those students were not fit to be doctors; those interns were not fit to be surgeons. The process worked. Or so we thought.
The epidemic of physician burnout has raised alarm in many healthcare organizations. This mental state, characterized by emotional exhaustion, depersonalization and a diminished sense of personal accomplishment, has adverse consequences for both patient and clinician. The statistics are sobering. More than half of physicians, by self-report, have symptoms of burnout. No clinician is immune. Significant numbers of nurses and residents are similarly affected. The trend is worrisome. Compared to 2011, the percentage of physicians with burnout symptoms has increased, and the percentage satisfied with their work/life balance has decreased. Burnout affects physicians across all specialties, but the picture is particularly grim for surgeons, and even a bit more so for vascular surgeons. Compared with 13 other surgical specialties, vascular surgeons report the second highest rate of burnout. They also report the lowest level of career satisfaction, ranked first in stating they may have chosen an alternate career if they could choose again, and first in recommending an alternate career to medicine to their children.
In light of these sobering data, it must become an increasing concern of SVS as our professional home, as well as APDVS, as the professional home for Program Directors in Vascular Surgery, when almost a third of vascular surgeons report depression, and when compared to other surgical specialties, the highest incidence of suicidal ideation occurs in our own colleagues. Perhaps most importantly, 70 percent of physicians who score in the lower third on the Physician Well-Being Index report their well-being as average or above average. So relying on introspection offers limited hope.
Burnout is also a patient care-quality issue. Patients who are cared for by clinicians suffering from burnout do not fare well. A burned-out physician may appear to colleagues as frustrated, cynical and even callous, and to his or her patients as lacking empathy and compassion. Only 53 percent of patients, when surveyed, believe the health care system provides compassionate care. Diabetic patients of physicians with high empathy scores had improved control of HbA1c, fewer hospitalizations and fewer serious complications. Similarly, those with cancer had improved psychological adjustment, decreased ICU utilization and an improved immune response.
What does this landscape look like to those starting their medical careers – our future vascular surgeons? As a rule, students enter medical school altruistic and idealistic, excited about becoming a doctor, empathic and eager to care for their future patients. What follows is a decline in compassion, a crucial ingredient to mitigate burnout. Their curriculum focuses on emotional detachment and affective distancing for the purpose of clinical neutrality. Twenty percent of medical school graduates reported that they experienced disconnects between what they were taught about professional behaviors and attitudes and what they saw demonstrated by their faculty. Empathy is further eroded as residents experience “time-constrained” patient interactions in the clinic, the emergency department and the operating room. They often work with frustrated and overwhelmed faculty members who are experiencing increased pressure to generate greater clinical revenue and struggle with non-intuitive electronic medical record systems.
By almost any metric, vascular surgeons’ work is stressful. They work long hours, spend considerable hours in the operating room (average 20 hours a week) and average 2.7 nights of call a week. The vascular surgery workforce needs to continue to increase in light of the aging population that generally is sicker, yet demanding of more active lives. The demand will not be met without improving the health of our workforce.
Burnout also leads to early retirement. And burnout predicts the future. Each one-point change on the emotional exhaustion burnout scale is associated with a 43 percent higher likelihood that the affected physicians will reduce their FTE over the ensuing 24 months. Compounding supply further are the issues at the front end. An alarming 69 percent of U.S. general surgery trainees meet the criteria for burnout, and 44 percent of the 753 general surgery residents sampled considered dropping out of their training program; an even greater proportion considered doing so if they had symptoms of burnout. Women in training were at a higher risk of burnout compared to men. Although a study of burnout and job satisfaction in members of the American College of Surgeons found that private-practice surgeons were more likely to experience burnout than surgeons practicing in academic settings, Elmore et. al. observed that residents who planned to enter private practice reported higher levels of burnout.
In summary, burnout out is real and is impacting the health, well-being, and careers of vascular surgeons. Burnout places both the surgeon and the patient at risk for a poor outcome. Burnout influences medical student and resident career choices. Burnout can no longer be ignored – doing nothing is not an option.
Can the Society of Vascular Surgery do anything to improve the well-being of its members? We will begin that discussion next month.
*The authors extend their thanks and appreciation for the guidance, resources and support of Michael Goldberg, M.D., Scholar in Residence, Schwartz Center for Compassionate Care, Boston, Mass., and Clinical Professor of Orthopedics at Seattle Children’s Hospital..
In my editorial in the November issue of Vascular Specialist I asked the question: Are we ok? I received many responses from members and I think the collective answer is best characterized as …maybe. Like nearly every other physician, I have witnessed the effects of burnout for my entire career. After high school, I enrolled in a BA/MD program with about 60 other students. Nearly half never matriculated. After medical school, I began a general surgery residency with seven other categorical interns. Six of them quit in the first year. What we now call burnout was once thought of as a process for weeding out those who could not “hack” it. Those students were not fit to be doctors; those interns were not fit to be surgeons. The process worked. Or so we thought.
The epidemic of physician burnout has raised alarm in many healthcare organizations. This mental state, characterized by emotional exhaustion, depersonalization and a diminished sense of personal accomplishment, has adverse consequences for both patient and clinician. The statistics are sobering. More than half of physicians, by self-report, have symptoms of burnout. No clinician is immune. Significant numbers of nurses and residents are similarly affected. The trend is worrisome. Compared to 2011, the percentage of physicians with burnout symptoms has increased, and the percentage satisfied with their work/life balance has decreased. Burnout affects physicians across all specialties, but the picture is particularly grim for surgeons, and even a bit more so for vascular surgeons. Compared with 13 other surgical specialties, vascular surgeons report the second highest rate of burnout. They also report the lowest level of career satisfaction, ranked first in stating they may have chosen an alternate career if they could choose again, and first in recommending an alternate career to medicine to their children.
In light of these sobering data, it must become an increasing concern of SVS as our professional home, as well as APDVS, as the professional home for Program Directors in Vascular Surgery, when almost a third of vascular surgeons report depression, and when compared to other surgical specialties, the highest incidence of suicidal ideation occurs in our own colleagues. Perhaps most importantly, 70 percent of physicians who score in the lower third on the Physician Well-Being Index report their well-being as average or above average. So relying on introspection offers limited hope.
Burnout is also a patient care-quality issue. Patients who are cared for by clinicians suffering from burnout do not fare well. A burned-out physician may appear to colleagues as frustrated, cynical and even callous, and to his or her patients as lacking empathy and compassion. Only 53 percent of patients, when surveyed, believe the health care system provides compassionate care. Diabetic patients of physicians with high empathy scores had improved control of HbA1c, fewer hospitalizations and fewer serious complications. Similarly, those with cancer had improved psychological adjustment, decreased ICU utilization and an improved immune response.
What does this landscape look like to those starting their medical careers – our future vascular surgeons? As a rule, students enter medical school altruistic and idealistic, excited about becoming a doctor, empathic and eager to care for their future patients. What follows is a decline in compassion, a crucial ingredient to mitigate burnout. Their curriculum focuses on emotional detachment and affective distancing for the purpose of clinical neutrality. Twenty percent of medical school graduates reported that they experienced disconnects between what they were taught about professional behaviors and attitudes and what they saw demonstrated by their faculty. Empathy is further eroded as residents experience “time-constrained” patient interactions in the clinic, the emergency department and the operating room. They often work with frustrated and overwhelmed faculty members who are experiencing increased pressure to generate greater clinical revenue and struggle with non-intuitive electronic medical record systems.
By almost any metric, vascular surgeons’ work is stressful. They work long hours, spend considerable hours in the operating room (average 20 hours a week) and average 2.7 nights of call a week. The vascular surgery workforce needs to continue to increase in light of the aging population that generally is sicker, yet demanding of more active lives. The demand will not be met without improving the health of our workforce.
Burnout also leads to early retirement. And burnout predicts the future. Each one-point change on the emotional exhaustion burnout scale is associated with a 43 percent higher likelihood that the affected physicians will reduce their FTE over the ensuing 24 months. Compounding supply further are the issues at the front end. An alarming 69 percent of U.S. general surgery trainees meet the criteria for burnout, and 44 percent of the 753 general surgery residents sampled considered dropping out of their training program; an even greater proportion considered doing so if they had symptoms of burnout. Women in training were at a higher risk of burnout compared to men. Although a study of burnout and job satisfaction in members of the American College of Surgeons found that private-practice surgeons were more likely to experience burnout than surgeons practicing in academic settings, Elmore et. al. observed that residents who planned to enter private practice reported higher levels of burnout.
In summary, burnout out is real and is impacting the health, well-being, and careers of vascular surgeons. Burnout places both the surgeon and the patient at risk for a poor outcome. Burnout influences medical student and resident career choices. Burnout can no longer be ignored – doing nothing is not an option.
Can the Society of Vascular Surgery do anything to improve the well-being of its members? We will begin that discussion next month.
*The authors extend their thanks and appreciation for the guidance, resources and support of Michael Goldberg, M.D., Scholar in Residence, Schwartz Center for Compassionate Care, Boston, Mass., and Clinical Professor of Orthopedics at Seattle Children’s Hospital..
Upper arm loop grafts
Many forearm loop grafts have multiple outflow interventions before failure. These angioplasties and outflow stents create inflammation around the vein just above the antecubital area. This inflammation makes arterial exposure difficult for a standard upper arm graft configuration. Accordingly, surgeons may avoid this area by performing an upper arm loop graft, which originates and terminates in one high arm incision. Upper arm loop grafts are also used for high bifurcation of the radial and ulnar arteries and when prior access grafts make other configurations difficult. Surgeons appear to place these upper arm loops routed with one limb running subcutaneously parallel to the brachial artery, placing half of the loop in an awkward position for cannulation.
Dr. Showalter is clinical assistant professor of surgery, Florida State University Medical School, Tallahassee, and attending vascular surgeon, Sarasota Vascular Specialists.
Many forearm loop grafts have multiple outflow interventions before failure. These angioplasties and outflow stents create inflammation around the vein just above the antecubital area. This inflammation makes arterial exposure difficult for a standard upper arm graft configuration. Accordingly, surgeons may avoid this area by performing an upper arm loop graft, which originates and terminates in one high arm incision. Upper arm loop grafts are also used for high bifurcation of the radial and ulnar arteries and when prior access grafts make other configurations difficult. Surgeons appear to place these upper arm loops routed with one limb running subcutaneously parallel to the brachial artery, placing half of the loop in an awkward position for cannulation.
Dr. Showalter is clinical assistant professor of surgery, Florida State University Medical School, Tallahassee, and attending vascular surgeon, Sarasota Vascular Specialists.
Many forearm loop grafts have multiple outflow interventions before failure. These angioplasties and outflow stents create inflammation around the vein just above the antecubital area. This inflammation makes arterial exposure difficult for a standard upper arm graft configuration. Accordingly, surgeons may avoid this area by performing an upper arm loop graft, which originates and terminates in one high arm incision. Upper arm loop grafts are also used for high bifurcation of the radial and ulnar arteries and when prior access grafts make other configurations difficult. Surgeons appear to place these upper arm loops routed with one limb running subcutaneously parallel to the brachial artery, placing half of the loop in an awkward position for cannulation.
Dr. Showalter is clinical assistant professor of surgery, Florida State University Medical School, Tallahassee, and attending vascular surgeon, Sarasota Vascular Specialists.