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Aspirin may protect against dementia in T2DM
ANAHEIM, CALIF. – in the randomized JPAD 2 study, Chisa Matsumoto, MD, reported at the American Heart Association scientific sessions.
The benefit was restricted to women with T2DM. During a median 9.7 years of follow-up, the incidence of dementia, as defined by prescription of antidementia drugs or hospitalization for dementia, was 2.7 cases per 1,000 person-years in women randomized to low-dose aspirin and 6 per 1,000 person-years in those assigned to standard care. This translated to a 60% relative risk reduction in a multivariate analysis adjusted for age, hypertension, dyslipidemia, smoking, and hemoglobin A1c level, according to Dr. Matsumoto of Hyogo (Japan) College of Medicine.
JPAD 2 was a multicenter prospective cohort study of 2,536 Japanese patients with T2DM who previously participated in the open-label randomized Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial, which ran from 2002 to 2008. Patients’ average age at baseline was 64 years; they had a 7-year duration of diabetes and no history of cardiovascular disease or dementia. When JPAD ended, patients continued on in JPAD 2, with follow-up through July 2015.
In the overall JPAD 2 population, the dementia incidence rate was 3.6 per 1,000 person-years in the low-dose aspirin group compared with 4.9 per 1,000 person-years in controls, for a highly significant 35% relative risk reduction in a fully adjusted multivariate intention to treat analysis.
During follow-up, 15% of patients switched from low-dose aspirin to no aspirin or vice versa, prompting Dr. Matsumoto and her coinvestigators to perform a per protocol analysis of the data. The results were essentially the same as in the intent-to-treat analysis.
JPAD 2 was the first-ever study to evaluate the long-term efficacy of low-dose aspirin for prevention of dementia specifically in patients with T2DM, a known risk factor for dementia. Other observational and randomized controlled studies have yielded inconsistent results. For example, a recent meta-analysis of five studies with a median 6-year follow-up found an 18% relative risk reduction in onset of dementia or cognitive impairment, a difference that didn’t achieve statistical significance (J Am Geriatr Soc. 2017 Aug;65[8]:1763-8).
Some prior studies have suggested there is a sex-based difference in the risk of dementia, which prompted Dr. Matsumoto and her coinvestigators to analyze the JPAD 2 results separately in men and women.
She was quick to acknowledge that the novel JPAD 2 findings cry out for replication in other studies with larger numbers and/or longer follow-up.
Session moderator Mary Cushman, MD, declared, “I think this is really exciting and interesting.”
Asked to speculate on the mechanism for the divergent efficacy of low-dose aspirin in men and women with T2DM in JPAD 2, Dr. Matsumoto said play of chance may have had a partial role. The incidence of dementia was roughly 50% greater in the JPAD 2 women than in the men, so the study may have been underpowered to look at the dementia rate in men. But there may be a biologic mechanism at work, as well: Apolipoprotein E4, which is linked to increased risk of dementia, is believed to interact with gender, she said.
Dr. Matsumoto reported having no financial conflicts.
SOURCE: Matsumoto C. AHA scientific sessions.
ANAHEIM, CALIF. – in the randomized JPAD 2 study, Chisa Matsumoto, MD, reported at the American Heart Association scientific sessions.
The benefit was restricted to women with T2DM. During a median 9.7 years of follow-up, the incidence of dementia, as defined by prescription of antidementia drugs or hospitalization for dementia, was 2.7 cases per 1,000 person-years in women randomized to low-dose aspirin and 6 per 1,000 person-years in those assigned to standard care. This translated to a 60% relative risk reduction in a multivariate analysis adjusted for age, hypertension, dyslipidemia, smoking, and hemoglobin A1c level, according to Dr. Matsumoto of Hyogo (Japan) College of Medicine.
JPAD 2 was a multicenter prospective cohort study of 2,536 Japanese patients with T2DM who previously participated in the open-label randomized Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial, which ran from 2002 to 2008. Patients’ average age at baseline was 64 years; they had a 7-year duration of diabetes and no history of cardiovascular disease or dementia. When JPAD ended, patients continued on in JPAD 2, with follow-up through July 2015.
In the overall JPAD 2 population, the dementia incidence rate was 3.6 per 1,000 person-years in the low-dose aspirin group compared with 4.9 per 1,000 person-years in controls, for a highly significant 35% relative risk reduction in a fully adjusted multivariate intention to treat analysis.
During follow-up, 15% of patients switched from low-dose aspirin to no aspirin or vice versa, prompting Dr. Matsumoto and her coinvestigators to perform a per protocol analysis of the data. The results were essentially the same as in the intent-to-treat analysis.
JPAD 2 was the first-ever study to evaluate the long-term efficacy of low-dose aspirin for prevention of dementia specifically in patients with T2DM, a known risk factor for dementia. Other observational and randomized controlled studies have yielded inconsistent results. For example, a recent meta-analysis of five studies with a median 6-year follow-up found an 18% relative risk reduction in onset of dementia or cognitive impairment, a difference that didn’t achieve statistical significance (J Am Geriatr Soc. 2017 Aug;65[8]:1763-8).
Some prior studies have suggested there is a sex-based difference in the risk of dementia, which prompted Dr. Matsumoto and her coinvestigators to analyze the JPAD 2 results separately in men and women.
She was quick to acknowledge that the novel JPAD 2 findings cry out for replication in other studies with larger numbers and/or longer follow-up.
Session moderator Mary Cushman, MD, declared, “I think this is really exciting and interesting.”
Asked to speculate on the mechanism for the divergent efficacy of low-dose aspirin in men and women with T2DM in JPAD 2, Dr. Matsumoto said play of chance may have had a partial role. The incidence of dementia was roughly 50% greater in the JPAD 2 women than in the men, so the study may have been underpowered to look at the dementia rate in men. But there may be a biologic mechanism at work, as well: Apolipoprotein E4, which is linked to increased risk of dementia, is believed to interact with gender, she said.
Dr. Matsumoto reported having no financial conflicts.
SOURCE: Matsumoto C. AHA scientific sessions.
ANAHEIM, CALIF. – in the randomized JPAD 2 study, Chisa Matsumoto, MD, reported at the American Heart Association scientific sessions.
The benefit was restricted to women with T2DM. During a median 9.7 years of follow-up, the incidence of dementia, as defined by prescription of antidementia drugs or hospitalization for dementia, was 2.7 cases per 1,000 person-years in women randomized to low-dose aspirin and 6 per 1,000 person-years in those assigned to standard care. This translated to a 60% relative risk reduction in a multivariate analysis adjusted for age, hypertension, dyslipidemia, smoking, and hemoglobin A1c level, according to Dr. Matsumoto of Hyogo (Japan) College of Medicine.
JPAD 2 was a multicenter prospective cohort study of 2,536 Japanese patients with T2DM who previously participated in the open-label randomized Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial, which ran from 2002 to 2008. Patients’ average age at baseline was 64 years; they had a 7-year duration of diabetes and no history of cardiovascular disease or dementia. When JPAD ended, patients continued on in JPAD 2, with follow-up through July 2015.
In the overall JPAD 2 population, the dementia incidence rate was 3.6 per 1,000 person-years in the low-dose aspirin group compared with 4.9 per 1,000 person-years in controls, for a highly significant 35% relative risk reduction in a fully adjusted multivariate intention to treat analysis.
During follow-up, 15% of patients switched from low-dose aspirin to no aspirin or vice versa, prompting Dr. Matsumoto and her coinvestigators to perform a per protocol analysis of the data. The results were essentially the same as in the intent-to-treat analysis.
JPAD 2 was the first-ever study to evaluate the long-term efficacy of low-dose aspirin for prevention of dementia specifically in patients with T2DM, a known risk factor for dementia. Other observational and randomized controlled studies have yielded inconsistent results. For example, a recent meta-analysis of five studies with a median 6-year follow-up found an 18% relative risk reduction in onset of dementia or cognitive impairment, a difference that didn’t achieve statistical significance (J Am Geriatr Soc. 2017 Aug;65[8]:1763-8).
Some prior studies have suggested there is a sex-based difference in the risk of dementia, which prompted Dr. Matsumoto and her coinvestigators to analyze the JPAD 2 results separately in men and women.
She was quick to acknowledge that the novel JPAD 2 findings cry out for replication in other studies with larger numbers and/or longer follow-up.
Session moderator Mary Cushman, MD, declared, “I think this is really exciting and interesting.”
Asked to speculate on the mechanism for the divergent efficacy of low-dose aspirin in men and women with T2DM in JPAD 2, Dr. Matsumoto said play of chance may have had a partial role. The incidence of dementia was roughly 50% greater in the JPAD 2 women than in the men, so the study may have been underpowered to look at the dementia rate in men. But there may be a biologic mechanism at work, as well: Apolipoprotein E4, which is linked to increased risk of dementia, is believed to interact with gender, she said.
Dr. Matsumoto reported having no financial conflicts.
SOURCE: Matsumoto C. AHA scientific sessions.
REPORTING FROM THE AHA SCIENTIFIC SESSIONS
Key clinical point:
Major finding: Daily low-dose aspirin reduced the incidence of dementia by more than one-third in patients with type 2 diabetes.
Study details: A multicenter randomized prospective cohort study of 2,536 patients with type 2 diabetes.
Disclosures: The study presenter reported having no financial conflicts.
Source: Matsumoto C. AHA scientific sessions.
Facing the world
***
Edgar is 86. His COPD recently caught up with him, and he needs oxygen. The nasal prongs that deliver it are irritating, but what really bothers him about them is that he won’t attend any activities in his assisted living facility wearing nasal prongs and trailing a tank.
***
Brenda comes in with a large bandage on her forehead. She takes it off to show me a large, jagged, fully-healed scar. Four months ago she gashed her head on an appliance and didn’t get medical help in time to have the wound properly stitched.
“My bangs aren’t thick enough to cover it,” she says. “My daughter asks why I wear a Band-Aid all the time,” says Brenda. But Brenda would rather walk around with a large bandage on her forehead. Just as Edgar won’t let anyone see him sick and diminished, Brenda won’t let anyone see her face damaged.
***
Stella has lymphoma. While she was on chemotherapy, she stayed put at home and avoided crowds to avoid catching someone’s virus. Once chemo was done, she was able to fly to Tallahassee, Fla., to see her new granddaughter Genevieve.
Unfortunately, her lymphoma recurred sooner than she and her doctors had hoped. Now Stella is on a new drug. This seems to be helping, but it puts her back at risk for infections in crowds.
And on planes. “Will you be able to visit Genevieve in Florida?” I ask.
Her husband Ben interjects. “Her doctors say she can,” he said, “but she would have to wear a mask on the plane, and Stella won’t wear a mask.”
***
Malcolm comes in now and then for this and that. This time, he is here for a skin check. At each visit he brings me up to date on an endless family lawsuit over a contested estate. Its subplots could script a whole Netflix series.
When I’m done with the skin check, Malcolm says, “also, I’d like Botox on my forehead.”
“OK,” I say. I don’t ask why, but Malcolm answers anyway.
“The lawsuit is finally coming to a head,” he says. “One of the nephews contesting the will is flying in from Indonesia, and the trial gets underway in Kentucky next week. I never would have started this fight, but since my charming relatives did, I’m in it to win it.”
I wish him luck.
“That’s why I want Botox,” he says. “I’m going to testify, and I want to look my confident best.”
Go, Malcolm!
While we’re talking Botox, I recall Amy, a well-traveled consultant who gave lectures all over.
“I’m curious,” I once asked her. “What do people say to you after you get Botox? Do they notice?”
“That’s interesting,” she said. “When I speak to groups, my face is projected onto large screens. That makes my wrinkles look like the Grand Canyon.
“When I started doing Botox, a man came over to me after a lecture and said, ‘I’ve heard you before, but this time you were, somehow, more cogent and compelling.’
“I thanked him, of course,” said Amy with a smile. “But the speech he was praising was the exact same speech he’d heard the first time.”
***
The rest of us try to put on the best face we can, assisted (in descending order of importance) by: makers of cosmetics, estheticians, dentists, plastic surgeons, and – oh yes – even dermatologists.
Happy to assist!
Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. Write to him at dermnews@frontlinemedcom.com.
***
Edgar is 86. His COPD recently caught up with him, and he needs oxygen. The nasal prongs that deliver it are irritating, but what really bothers him about them is that he won’t attend any activities in his assisted living facility wearing nasal prongs and trailing a tank.
***
Brenda comes in with a large bandage on her forehead. She takes it off to show me a large, jagged, fully-healed scar. Four months ago she gashed her head on an appliance and didn’t get medical help in time to have the wound properly stitched.
“My bangs aren’t thick enough to cover it,” she says. “My daughter asks why I wear a Band-Aid all the time,” says Brenda. But Brenda would rather walk around with a large bandage on her forehead. Just as Edgar won’t let anyone see him sick and diminished, Brenda won’t let anyone see her face damaged.
***
Stella has lymphoma. While she was on chemotherapy, she stayed put at home and avoided crowds to avoid catching someone’s virus. Once chemo was done, she was able to fly to Tallahassee, Fla., to see her new granddaughter Genevieve.
Unfortunately, her lymphoma recurred sooner than she and her doctors had hoped. Now Stella is on a new drug. This seems to be helping, but it puts her back at risk for infections in crowds.
And on planes. “Will you be able to visit Genevieve in Florida?” I ask.
Her husband Ben interjects. “Her doctors say she can,” he said, “but she would have to wear a mask on the plane, and Stella won’t wear a mask.”
***
Malcolm comes in now and then for this and that. This time, he is here for a skin check. At each visit he brings me up to date on an endless family lawsuit over a contested estate. Its subplots could script a whole Netflix series.
When I’m done with the skin check, Malcolm says, “also, I’d like Botox on my forehead.”
“OK,” I say. I don’t ask why, but Malcolm answers anyway.
“The lawsuit is finally coming to a head,” he says. “One of the nephews contesting the will is flying in from Indonesia, and the trial gets underway in Kentucky next week. I never would have started this fight, but since my charming relatives did, I’m in it to win it.”
I wish him luck.
“That’s why I want Botox,” he says. “I’m going to testify, and I want to look my confident best.”
Go, Malcolm!
While we’re talking Botox, I recall Amy, a well-traveled consultant who gave lectures all over.
“I’m curious,” I once asked her. “What do people say to you after you get Botox? Do they notice?”
“That’s interesting,” she said. “When I speak to groups, my face is projected onto large screens. That makes my wrinkles look like the Grand Canyon.
“When I started doing Botox, a man came over to me after a lecture and said, ‘I’ve heard you before, but this time you were, somehow, more cogent and compelling.’
“I thanked him, of course,” said Amy with a smile. “But the speech he was praising was the exact same speech he’d heard the first time.”
***
The rest of us try to put on the best face we can, assisted (in descending order of importance) by: makers of cosmetics, estheticians, dentists, plastic surgeons, and – oh yes – even dermatologists.
Happy to assist!
Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. Write to him at dermnews@frontlinemedcom.com.
***
Edgar is 86. His COPD recently caught up with him, and he needs oxygen. The nasal prongs that deliver it are irritating, but what really bothers him about them is that he won’t attend any activities in his assisted living facility wearing nasal prongs and trailing a tank.
***
Brenda comes in with a large bandage on her forehead. She takes it off to show me a large, jagged, fully-healed scar. Four months ago she gashed her head on an appliance and didn’t get medical help in time to have the wound properly stitched.
“My bangs aren’t thick enough to cover it,” she says. “My daughter asks why I wear a Band-Aid all the time,” says Brenda. But Brenda would rather walk around with a large bandage on her forehead. Just as Edgar won’t let anyone see him sick and diminished, Brenda won’t let anyone see her face damaged.
***
Stella has lymphoma. While she was on chemotherapy, she stayed put at home and avoided crowds to avoid catching someone’s virus. Once chemo was done, she was able to fly to Tallahassee, Fla., to see her new granddaughter Genevieve.
Unfortunately, her lymphoma recurred sooner than she and her doctors had hoped. Now Stella is on a new drug. This seems to be helping, but it puts her back at risk for infections in crowds.
And on planes. “Will you be able to visit Genevieve in Florida?” I ask.
Her husband Ben interjects. “Her doctors say she can,” he said, “but she would have to wear a mask on the plane, and Stella won’t wear a mask.”
***
Malcolm comes in now and then for this and that. This time, he is here for a skin check. At each visit he brings me up to date on an endless family lawsuit over a contested estate. Its subplots could script a whole Netflix series.
When I’m done with the skin check, Malcolm says, “also, I’d like Botox on my forehead.”
“OK,” I say. I don’t ask why, but Malcolm answers anyway.
“The lawsuit is finally coming to a head,” he says. “One of the nephews contesting the will is flying in from Indonesia, and the trial gets underway in Kentucky next week. I never would have started this fight, but since my charming relatives did, I’m in it to win it.”
I wish him luck.
“That’s why I want Botox,” he says. “I’m going to testify, and I want to look my confident best.”
Go, Malcolm!
While we’re talking Botox, I recall Amy, a well-traveled consultant who gave lectures all over.
“I’m curious,” I once asked her. “What do people say to you after you get Botox? Do they notice?”
“That’s interesting,” she said. “When I speak to groups, my face is projected onto large screens. That makes my wrinkles look like the Grand Canyon.
“When I started doing Botox, a man came over to me after a lecture and said, ‘I’ve heard you before, but this time you were, somehow, more cogent and compelling.’
“I thanked him, of course,” said Amy with a smile. “But the speech he was praising was the exact same speech he’d heard the first time.”
***
The rest of us try to put on the best face we can, assisted (in descending order of importance) by: makers of cosmetics, estheticians, dentists, plastic surgeons, and – oh yes – even dermatologists.
Happy to assist!
Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. Write to him at dermnews@frontlinemedcom.com.
Acalabrutinib shows less off-target activity in mantle cell lymphoma
A new Bruton tyrosine kinase inhibitor has shown a high response rate and favorable safety profile in the treatment of patients with mantle cell lymphoma.
Researchers reported the results of an open-label, phase 2 study of oral acalabrutinib (100 mg, twice daily) in 124 patients with relapsed or refractory mantle cell lymphoma in The Lancet. Acalabrutinib (Calquence) received accelerated approval from the Food and Drug Administration in October 2017 for treatment of adults with mantle cell lymphoma who have received at least one prior therapy.
The Bruton tyrosine kinase (BTK) inhibitor ibrutinib (Imbruvica), which was approved in 2013 for the treatment of mantle cell lymphoma, has been associated with side effects including atrial fibrillation, infections and bleeding, likely due to its off-target activity against other kinases. But acalabrutinib (ACP-196) “is a highly selective, potent BTK inhibitor developed to minimise off-target activity,” wrote Michael Wang, MD, of the department of lymphoma and myeloma at the University of Texas MD Anderson Cancer Center, Houston, and his colleagues.
After a median follow-up of 15.2 months, 81% of patients in the study achieved an investigator-assessed overall response based on Lugano classification, with 40% achieving a complete response. The results were similar according to an independent review committee evaluation of responses based on CT and PET scans, bone-marrow biopsy specimens, endoscopy results, and clinical data.
There was also a reduction in lymphadenopathy seen in 94% of patients. The patients who showed a complete response took a median of 3.4 months to get there, and the median time to best response was 1.9 months.
The researchers also looked at response rates across a number of prespecified subgroups. Patients with Ann Arbor stage IV disease, those with bone marrow involvement, and those with extranodal disease were less likely to achieve a complete response (29%, 14% and 28% respectively). Patients with lymph nodes 5 cm or larger in diameter showed a 78% response rate.
While the Kaplan-Meier estimated medians for duration of response, progression-free survival, and overall survival were not reached, 87% of patients achieved 12-month overall survival and 67% of patients achieved progression-free survival at 12 months.
Most of the adverse events were grade 1 or 2, and included headache, diarrhea, fatigue, and myalgia.
There were no grade 4 or 5 adverse events, but 10% of patients experienced neutropenia, 9% experienced anemia and 5% experienced pneumonia. There was also one case of grade 3 or worse hemorrhage, but no cases of atrial fibrillation. Lymphocytosis was seen in 31% of patients.
Nearly half of patients (44%) discontinued treatment, mostly because of progressive disease (31%) but 6% discontinued the treatment because of adverse events.
“Overall, treatment with acalabrutinib demonstrated a favourable benefit-risk profile and represents a promising treatment option for patients with relapsed or refractory mantle cell lymphoma,” the researchers wrote. “Data from the ongoing ACE-CL-006 trial directly comparing acalabrutinib with ibrutinib in previously treated patients with high-risk chronic lymphocytic leukaemia will further differentiate the safety profiles of the two treatments.”
The researchers noted a decrease in plasma levels of tumor necrosis factor alpha, the cytokine CXCL13, and other cytokines known to be involved in inflammation and cell trafficking.
“These findings add to the growing body of evidence indicating that BTK inhibition disrupts the tumour microenvironment, limiting the supply of cytokines and chemokines necessary for complex interactions with stromal and accessory cells important for tumour growth and survival.”
The study was sponsored by Acerta Pharma, a member of the AstraZeneca Group. Several study authors reported grants, personal fees and other support from the pharmaceutical industry, including Acerta Pharma, most outside the submitted work. Several authors were also employees of Acerta and some had acalabrutinib patents pending or issued.
hematologynews@frontlinemedcom.com
SOURCE: Wang M et al., Lancet. 2018;391:659-67.
A new Bruton tyrosine kinase inhibitor has shown a high response rate and favorable safety profile in the treatment of patients with mantle cell lymphoma.
Researchers reported the results of an open-label, phase 2 study of oral acalabrutinib (100 mg, twice daily) in 124 patients with relapsed or refractory mantle cell lymphoma in The Lancet. Acalabrutinib (Calquence) received accelerated approval from the Food and Drug Administration in October 2017 for treatment of adults with mantle cell lymphoma who have received at least one prior therapy.
The Bruton tyrosine kinase (BTK) inhibitor ibrutinib (Imbruvica), which was approved in 2013 for the treatment of mantle cell lymphoma, has been associated with side effects including atrial fibrillation, infections and bleeding, likely due to its off-target activity against other kinases. But acalabrutinib (ACP-196) “is a highly selective, potent BTK inhibitor developed to minimise off-target activity,” wrote Michael Wang, MD, of the department of lymphoma and myeloma at the University of Texas MD Anderson Cancer Center, Houston, and his colleagues.
After a median follow-up of 15.2 months, 81% of patients in the study achieved an investigator-assessed overall response based on Lugano classification, with 40% achieving a complete response. The results were similar according to an independent review committee evaluation of responses based on CT and PET scans, bone-marrow biopsy specimens, endoscopy results, and clinical data.
There was also a reduction in lymphadenopathy seen in 94% of patients. The patients who showed a complete response took a median of 3.4 months to get there, and the median time to best response was 1.9 months.
The researchers also looked at response rates across a number of prespecified subgroups. Patients with Ann Arbor stage IV disease, those with bone marrow involvement, and those with extranodal disease were less likely to achieve a complete response (29%, 14% and 28% respectively). Patients with lymph nodes 5 cm or larger in diameter showed a 78% response rate.
While the Kaplan-Meier estimated medians for duration of response, progression-free survival, and overall survival were not reached, 87% of patients achieved 12-month overall survival and 67% of patients achieved progression-free survival at 12 months.
Most of the adverse events were grade 1 or 2, and included headache, diarrhea, fatigue, and myalgia.
There were no grade 4 or 5 adverse events, but 10% of patients experienced neutropenia, 9% experienced anemia and 5% experienced pneumonia. There was also one case of grade 3 or worse hemorrhage, but no cases of atrial fibrillation. Lymphocytosis was seen in 31% of patients.
Nearly half of patients (44%) discontinued treatment, mostly because of progressive disease (31%) but 6% discontinued the treatment because of adverse events.
“Overall, treatment with acalabrutinib demonstrated a favourable benefit-risk profile and represents a promising treatment option for patients with relapsed or refractory mantle cell lymphoma,” the researchers wrote. “Data from the ongoing ACE-CL-006 trial directly comparing acalabrutinib with ibrutinib in previously treated patients with high-risk chronic lymphocytic leukaemia will further differentiate the safety profiles of the two treatments.”
The researchers noted a decrease in plasma levels of tumor necrosis factor alpha, the cytokine CXCL13, and other cytokines known to be involved in inflammation and cell trafficking.
“These findings add to the growing body of evidence indicating that BTK inhibition disrupts the tumour microenvironment, limiting the supply of cytokines and chemokines necessary for complex interactions with stromal and accessory cells important for tumour growth and survival.”
The study was sponsored by Acerta Pharma, a member of the AstraZeneca Group. Several study authors reported grants, personal fees and other support from the pharmaceutical industry, including Acerta Pharma, most outside the submitted work. Several authors were also employees of Acerta and some had acalabrutinib patents pending or issued.
hematologynews@frontlinemedcom.com
SOURCE: Wang M et al., Lancet. 2018;391:659-67.
A new Bruton tyrosine kinase inhibitor has shown a high response rate and favorable safety profile in the treatment of patients with mantle cell lymphoma.
Researchers reported the results of an open-label, phase 2 study of oral acalabrutinib (100 mg, twice daily) in 124 patients with relapsed or refractory mantle cell lymphoma in The Lancet. Acalabrutinib (Calquence) received accelerated approval from the Food and Drug Administration in October 2017 for treatment of adults with mantle cell lymphoma who have received at least one prior therapy.
The Bruton tyrosine kinase (BTK) inhibitor ibrutinib (Imbruvica), which was approved in 2013 for the treatment of mantle cell lymphoma, has been associated with side effects including atrial fibrillation, infections and bleeding, likely due to its off-target activity against other kinases. But acalabrutinib (ACP-196) “is a highly selective, potent BTK inhibitor developed to minimise off-target activity,” wrote Michael Wang, MD, of the department of lymphoma and myeloma at the University of Texas MD Anderson Cancer Center, Houston, and his colleagues.
After a median follow-up of 15.2 months, 81% of patients in the study achieved an investigator-assessed overall response based on Lugano classification, with 40% achieving a complete response. The results were similar according to an independent review committee evaluation of responses based on CT and PET scans, bone-marrow biopsy specimens, endoscopy results, and clinical data.
There was also a reduction in lymphadenopathy seen in 94% of patients. The patients who showed a complete response took a median of 3.4 months to get there, and the median time to best response was 1.9 months.
The researchers also looked at response rates across a number of prespecified subgroups. Patients with Ann Arbor stage IV disease, those with bone marrow involvement, and those with extranodal disease were less likely to achieve a complete response (29%, 14% and 28% respectively). Patients with lymph nodes 5 cm or larger in diameter showed a 78% response rate.
While the Kaplan-Meier estimated medians for duration of response, progression-free survival, and overall survival were not reached, 87% of patients achieved 12-month overall survival and 67% of patients achieved progression-free survival at 12 months.
Most of the adverse events were grade 1 or 2, and included headache, diarrhea, fatigue, and myalgia.
There were no grade 4 or 5 adverse events, but 10% of patients experienced neutropenia, 9% experienced anemia and 5% experienced pneumonia. There was also one case of grade 3 or worse hemorrhage, but no cases of atrial fibrillation. Lymphocytosis was seen in 31% of patients.
Nearly half of patients (44%) discontinued treatment, mostly because of progressive disease (31%) but 6% discontinued the treatment because of adverse events.
“Overall, treatment with acalabrutinib demonstrated a favourable benefit-risk profile and represents a promising treatment option for patients with relapsed or refractory mantle cell lymphoma,” the researchers wrote. “Data from the ongoing ACE-CL-006 trial directly comparing acalabrutinib with ibrutinib in previously treated patients with high-risk chronic lymphocytic leukaemia will further differentiate the safety profiles of the two treatments.”
The researchers noted a decrease in plasma levels of tumor necrosis factor alpha, the cytokine CXCL13, and other cytokines known to be involved in inflammation and cell trafficking.
“These findings add to the growing body of evidence indicating that BTK inhibition disrupts the tumour microenvironment, limiting the supply of cytokines and chemokines necessary for complex interactions with stromal and accessory cells important for tumour growth and survival.”
The study was sponsored by Acerta Pharma, a member of the AstraZeneca Group. Several study authors reported grants, personal fees and other support from the pharmaceutical industry, including Acerta Pharma, most outside the submitted work. Several authors were also employees of Acerta and some had acalabrutinib patents pending or issued.
hematologynews@frontlinemedcom.com
SOURCE: Wang M et al., Lancet. 2018;391:659-67.
FROM THE LANCET
Key clinical point:
Major finding: Eighty-one percent of patients with relapsed or refractory mantle cell lymphoma showed a partial or complete response to Bruton tyrosine kinase inhibitor acalabrutinib.
Study details: An open-label, phase 2 study in 124 patients with relapsed or refractory mantle cell lymphoma.
Disclosures: The study was sponsored by Acerta Pharma, a member of the AstraZeneca Group. Several study authors reported grants, personal fees and other support from the pharmaceutical industry, including Acerta Pharma, most outside the submitted work. Several authors were also employees of Acerta and some had acalabrutinib patents pending or issued.
Source: Wang M et al. Lancet. 2018;391:659-67.
Prostate cancer survival similar with EBRT/brachytherapy or surgery, analysts claim
More fuel for the radiation vs. surgery in prostate cancer debate comes from a study suggesting that patients with high-risk localized prostate cancer treated with external beam radiotherapy (EBRT) plus brachytherapy – with or without androgen deprivation (AD) – have survival rates equivalent to those of patients treated with radical prostatectomy (RP).
However, patients treated with EBRT and androgen deprivation without brachytherapy had significantly worse survival compared with patients treated with surgery, according to Ronald D. Ennis, MD, of Rutgers Cancer Institute of New Jersey, New Brunswick, and his colleagues.
“The data reported herein suggest that RT plus brachytherapy with or without AD and RP are associated with similar survival. This finding reinforces the need for patients to seek opinions from both a urologic oncologic surgeon with expertise in RP and a radiation oncologist with expertise in brachytherapy. The natural human tendency for physicians to prefer their modality necessitates this dual consultation approach, preferably in a single joint consultation visit,” the researchers wrote. The report was published in the Journal of Clinical Oncology.
The investigators attempted to control for variables that could influence the results by drawing on data on a large number of patients – 42,765 – who were treated at a large number of facilities across the United States. In addition, they incorporated data on clinical stage and Gleason score for all patients, prostate-specific antigen measurements, comorbidities, and socioeconomic factors that are either known or thought to influence treatment decisions.
They used inverse probability of treatment weight to adjust for imbalances of covariables among the treatment groups, and then created weighted time-dependent Cox proportional hazard models to estimate the effects of each type of treatment on survival.
Their sample included 24,688 patients who underwent RP, 15,435 who received EBRT with AD, and 2,642 who underwent EBRT and brachytherapy with or without AD.
They found no statistical difference in survival between RP and EBRT plus brachytherapy with/without AD in inverse probability of treatment weighted analysis. The hazard ratio for EBRT/brachytherapy was 1.17, but this was not statistically significant (95% confidence interval, 0.88-1.55).
In contrast. EBRT plus AD was associated with significantly worse survival, with a hazard ration of 1.53 (95% CI, 1.22-1.92).
The authors noted that “this finding reinforces the importance of complications, particularly in the urinary, sexual, and bowel domains, in combination with patient priorities and preferences, in determining an individual patient’s optimal choice. Significant data have been published in recent years regarding patient-reported outcomes that should be shared with all new patients to help guide them to their personal optimal treatment.”
They added that for some patients, quality of life may be a more important factor than survival when choosing a treatment modality.
SOURCE: Ennis et al. J Clin Oncol. 2018 Feb 28. doi: 10.1200/JCO.2017.75.9134
Clinicians interpreting this and other retrospective studies using large cancer registry data need to consider:
1) Whether treatment groups are comparable. For most retrospective studies, treatment groups are not comparable. Surgery versus RT is especially difficult to compare. In many studies in various cancers that have compared surgery alone versus surgery plus adjuvant therapy, the latter patients are inherently healthier. The ability or inability of investigators to address these confounding issues is central to assessing the quality of the evidence in a study.
(2) Limitations related to the data elements that are contained in the registry and data accuracy.
(3) Whether the results are believable clinically. If survival is the endpoint in a study, when do the survival curves separate – and is that consistent with the known clinical course of a particular disease? The main advantage of randomized trials is the ability to create comparable patient groups and minimize confounding, which is also the biggest limitation of retrospective studies. In clinical scenarios where multiple randomized trials have consistently confirmed a result (e.g., adding androgen deprivation therapy to RT improves survival for high-risk patients), repeated retrospective analyses asking these same questions that may show either the same or an opposite result are less useful.
Perhaps the biggest challenge in conducting studies using cancer registry data and interpreting their results as researchers and clinicians relates to the personal biases most of us harbor; these biases tempt us to analyze registry data in an attempt to refute clinical trials and to selectively believe studies that provide results supporting our own biases. For each clinician interpreting retrospective results along with or in absence of clinical trial data, recognizing our own biases by following the framework outlined previously to assess the quality and believability of each study can potentially remove the greatest confounder of all.
Ronald C. Chen, MD, MPH, is associate professor of radiation oncology at the University of North Carolina at Chapel Hill. He serves in a consulting or advisory role for Medivation/Astellas, Accuray, and Bayer, and has received research funding from Accuray. His remarks are adapted from an editorial (J Clin Oncol. 2018 Feb 28. doi: 0.1200/JCO.2017.77.5833).
Clinicians interpreting this and other retrospective studies using large cancer registry data need to consider:
1) Whether treatment groups are comparable. For most retrospective studies, treatment groups are not comparable. Surgery versus RT is especially difficult to compare. In many studies in various cancers that have compared surgery alone versus surgery plus adjuvant therapy, the latter patients are inherently healthier. The ability or inability of investigators to address these confounding issues is central to assessing the quality of the evidence in a study.
(2) Limitations related to the data elements that are contained in the registry and data accuracy.
(3) Whether the results are believable clinically. If survival is the endpoint in a study, when do the survival curves separate – and is that consistent with the known clinical course of a particular disease? The main advantage of randomized trials is the ability to create comparable patient groups and minimize confounding, which is also the biggest limitation of retrospective studies. In clinical scenarios where multiple randomized trials have consistently confirmed a result (e.g., adding androgen deprivation therapy to RT improves survival for high-risk patients), repeated retrospective analyses asking these same questions that may show either the same or an opposite result are less useful.
Perhaps the biggest challenge in conducting studies using cancer registry data and interpreting their results as researchers and clinicians relates to the personal biases most of us harbor; these biases tempt us to analyze registry data in an attempt to refute clinical trials and to selectively believe studies that provide results supporting our own biases. For each clinician interpreting retrospective results along with or in absence of clinical trial data, recognizing our own biases by following the framework outlined previously to assess the quality and believability of each study can potentially remove the greatest confounder of all.
Ronald C. Chen, MD, MPH, is associate professor of radiation oncology at the University of North Carolina at Chapel Hill. He serves in a consulting or advisory role for Medivation/Astellas, Accuray, and Bayer, and has received research funding from Accuray. His remarks are adapted from an editorial (J Clin Oncol. 2018 Feb 28. doi: 0.1200/JCO.2017.77.5833).
Clinicians interpreting this and other retrospective studies using large cancer registry data need to consider:
1) Whether treatment groups are comparable. For most retrospective studies, treatment groups are not comparable. Surgery versus RT is especially difficult to compare. In many studies in various cancers that have compared surgery alone versus surgery plus adjuvant therapy, the latter patients are inherently healthier. The ability or inability of investigators to address these confounding issues is central to assessing the quality of the evidence in a study.
(2) Limitations related to the data elements that are contained in the registry and data accuracy.
(3) Whether the results are believable clinically. If survival is the endpoint in a study, when do the survival curves separate – and is that consistent with the known clinical course of a particular disease? The main advantage of randomized trials is the ability to create comparable patient groups and minimize confounding, which is also the biggest limitation of retrospective studies. In clinical scenarios where multiple randomized trials have consistently confirmed a result (e.g., adding androgen deprivation therapy to RT improves survival for high-risk patients), repeated retrospective analyses asking these same questions that may show either the same or an opposite result are less useful.
Perhaps the biggest challenge in conducting studies using cancer registry data and interpreting their results as researchers and clinicians relates to the personal biases most of us harbor; these biases tempt us to analyze registry data in an attempt to refute clinical trials and to selectively believe studies that provide results supporting our own biases. For each clinician interpreting retrospective results along with or in absence of clinical trial data, recognizing our own biases by following the framework outlined previously to assess the quality and believability of each study can potentially remove the greatest confounder of all.
Ronald C. Chen, MD, MPH, is associate professor of radiation oncology at the University of North Carolina at Chapel Hill. He serves in a consulting or advisory role for Medivation/Astellas, Accuray, and Bayer, and has received research funding from Accuray. His remarks are adapted from an editorial (J Clin Oncol. 2018 Feb 28. doi: 0.1200/JCO.2017.77.5833).
More fuel for the radiation vs. surgery in prostate cancer debate comes from a study suggesting that patients with high-risk localized prostate cancer treated with external beam radiotherapy (EBRT) plus brachytherapy – with or without androgen deprivation (AD) – have survival rates equivalent to those of patients treated with radical prostatectomy (RP).
However, patients treated with EBRT and androgen deprivation without brachytherapy had significantly worse survival compared with patients treated with surgery, according to Ronald D. Ennis, MD, of Rutgers Cancer Institute of New Jersey, New Brunswick, and his colleagues.
“The data reported herein suggest that RT plus brachytherapy with or without AD and RP are associated with similar survival. This finding reinforces the need for patients to seek opinions from both a urologic oncologic surgeon with expertise in RP and a radiation oncologist with expertise in brachytherapy. The natural human tendency for physicians to prefer their modality necessitates this dual consultation approach, preferably in a single joint consultation visit,” the researchers wrote. The report was published in the Journal of Clinical Oncology.
The investigators attempted to control for variables that could influence the results by drawing on data on a large number of patients – 42,765 – who were treated at a large number of facilities across the United States. In addition, they incorporated data on clinical stage and Gleason score for all patients, prostate-specific antigen measurements, comorbidities, and socioeconomic factors that are either known or thought to influence treatment decisions.
They used inverse probability of treatment weight to adjust for imbalances of covariables among the treatment groups, and then created weighted time-dependent Cox proportional hazard models to estimate the effects of each type of treatment on survival.
Their sample included 24,688 patients who underwent RP, 15,435 who received EBRT with AD, and 2,642 who underwent EBRT and brachytherapy with or without AD.
They found no statistical difference in survival between RP and EBRT plus brachytherapy with/without AD in inverse probability of treatment weighted analysis. The hazard ratio for EBRT/brachytherapy was 1.17, but this was not statistically significant (95% confidence interval, 0.88-1.55).
In contrast. EBRT plus AD was associated with significantly worse survival, with a hazard ration of 1.53 (95% CI, 1.22-1.92).
The authors noted that “this finding reinforces the importance of complications, particularly in the urinary, sexual, and bowel domains, in combination with patient priorities and preferences, in determining an individual patient’s optimal choice. Significant data have been published in recent years regarding patient-reported outcomes that should be shared with all new patients to help guide them to their personal optimal treatment.”
They added that for some patients, quality of life may be a more important factor than survival when choosing a treatment modality.
SOURCE: Ennis et al. J Clin Oncol. 2018 Feb 28. doi: 10.1200/JCO.2017.75.9134
More fuel for the radiation vs. surgery in prostate cancer debate comes from a study suggesting that patients with high-risk localized prostate cancer treated with external beam radiotherapy (EBRT) plus brachytherapy – with or without androgen deprivation (AD) – have survival rates equivalent to those of patients treated with radical prostatectomy (RP).
However, patients treated with EBRT and androgen deprivation without brachytherapy had significantly worse survival compared with patients treated with surgery, according to Ronald D. Ennis, MD, of Rutgers Cancer Institute of New Jersey, New Brunswick, and his colleagues.
“The data reported herein suggest that RT plus brachytherapy with or without AD and RP are associated with similar survival. This finding reinforces the need for patients to seek opinions from both a urologic oncologic surgeon with expertise in RP and a radiation oncologist with expertise in brachytherapy. The natural human tendency for physicians to prefer their modality necessitates this dual consultation approach, preferably in a single joint consultation visit,” the researchers wrote. The report was published in the Journal of Clinical Oncology.
The investigators attempted to control for variables that could influence the results by drawing on data on a large number of patients – 42,765 – who were treated at a large number of facilities across the United States. In addition, they incorporated data on clinical stage and Gleason score for all patients, prostate-specific antigen measurements, comorbidities, and socioeconomic factors that are either known or thought to influence treatment decisions.
They used inverse probability of treatment weight to adjust for imbalances of covariables among the treatment groups, and then created weighted time-dependent Cox proportional hazard models to estimate the effects of each type of treatment on survival.
Their sample included 24,688 patients who underwent RP, 15,435 who received EBRT with AD, and 2,642 who underwent EBRT and brachytherapy with or without AD.
They found no statistical difference in survival between RP and EBRT plus brachytherapy with/without AD in inverse probability of treatment weighted analysis. The hazard ratio for EBRT/brachytherapy was 1.17, but this was not statistically significant (95% confidence interval, 0.88-1.55).
In contrast. EBRT plus AD was associated with significantly worse survival, with a hazard ration of 1.53 (95% CI, 1.22-1.92).
The authors noted that “this finding reinforces the importance of complications, particularly in the urinary, sexual, and bowel domains, in combination with patient priorities and preferences, in determining an individual patient’s optimal choice. Significant data have been published in recent years regarding patient-reported outcomes that should be shared with all new patients to help guide them to their personal optimal treatment.”
They added that for some patients, quality of life may be a more important factor than survival when choosing a treatment modality.
SOURCE: Ennis et al. J Clin Oncol. 2018 Feb 28. doi: 10.1200/JCO.2017.75.9134
FROM JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: This analysis of cancer registry data suggests that surgery and external beam radiotherapy plus brachytherapy have similar survival outcomes in patients with localized high-risk cancers.
Major finding: The hazard ratio for EBRT/brachytherapy vs. radical prostatectomy was 1.17 and was not statistically significant.
Data source: Retrospective review of data on 42,765 patients with localized high-risk prostate cancer.
Disclosures: No funding source was reported. Coauthor Madhu Mazumdar, PhD, reported National Cancer Institute funding. All other authors had no disclosures.
Source: Ennis et al. J Clin Oncol. 2018 Feb 28. doi: 10.1200/JCO.2017.75.9134.
Experts cite five orthopedic tests that physicians and patients should question
The American Academy of Pediatrics–Section on Orthopaedics and the Pediatric Orthopaedic Society of North America (POSNA) provide the following list:
- Do not order a screening hip ultrasound to rule out developmental hip dysplasia or developmental hip dislocation if the baby has no risk factors and has a clinically stable hip examination.
- Do not order radiographs or advise bracing or surgery for a child less than 8 years of age with simple in-toeing gait.
- Do not order custom orthotics or shoe inserts for a child with minimally symptomatic or asymptomatic flat feet.
- Do not order advanced imaging studies (MRI or CT) for most musculoskeletal conditions in a child until all appropriate clinical, laboratory, and plain radiographic examinations have been completed.
- Do not order follow-up x-rays for buckle (or torus) fractures if they are no longer tender or painful.
This list was developed based on data collected from 2014-2015 from the POSNA Evidence Based Committee and Advocacy Committee. Approximately 20 members of the two committees participated in the process. They submitted five items each from their practices and experience of tests or procedures that they found were commonly overutilized. The items were placed in order of number of times listed by each surgeon; a total of 30 items were submitted. The two committees then agreed on a final list of five procedures, based on frequency of responses and importance of the condition. After the list was reviewed and feedback provided, the POSNA board of directors voted on a final list. The AAP Executive Committee then provided final approval.
The committee noted that the list is provided for informational purposes and is not intended as a substitute for consultation with a physician.
Read the full list with more details here.
The American Academy of Pediatrics–Section on Orthopaedics and the Pediatric Orthopaedic Society of North America (POSNA) provide the following list:
- Do not order a screening hip ultrasound to rule out developmental hip dysplasia or developmental hip dislocation if the baby has no risk factors and has a clinically stable hip examination.
- Do not order radiographs or advise bracing or surgery for a child less than 8 years of age with simple in-toeing gait.
- Do not order custom orthotics or shoe inserts for a child with minimally symptomatic or asymptomatic flat feet.
- Do not order advanced imaging studies (MRI or CT) for most musculoskeletal conditions in a child until all appropriate clinical, laboratory, and plain radiographic examinations have been completed.
- Do not order follow-up x-rays for buckle (or torus) fractures if they are no longer tender or painful.
This list was developed based on data collected from 2014-2015 from the POSNA Evidence Based Committee and Advocacy Committee. Approximately 20 members of the two committees participated in the process. They submitted five items each from their practices and experience of tests or procedures that they found were commonly overutilized. The items were placed in order of number of times listed by each surgeon; a total of 30 items were submitted. The two committees then agreed on a final list of five procedures, based on frequency of responses and importance of the condition. After the list was reviewed and feedback provided, the POSNA board of directors voted on a final list. The AAP Executive Committee then provided final approval.
The committee noted that the list is provided for informational purposes and is not intended as a substitute for consultation with a physician.
Read the full list with more details here.
The American Academy of Pediatrics–Section on Orthopaedics and the Pediatric Orthopaedic Society of North America (POSNA) provide the following list:
- Do not order a screening hip ultrasound to rule out developmental hip dysplasia or developmental hip dislocation if the baby has no risk factors and has a clinically stable hip examination.
- Do not order radiographs or advise bracing or surgery for a child less than 8 years of age with simple in-toeing gait.
- Do not order custom orthotics or shoe inserts for a child with minimally symptomatic or asymptomatic flat feet.
- Do not order advanced imaging studies (MRI or CT) for most musculoskeletal conditions in a child until all appropriate clinical, laboratory, and plain radiographic examinations have been completed.
- Do not order follow-up x-rays for buckle (or torus) fractures if they are no longer tender or painful.
This list was developed based on data collected from 2014-2015 from the POSNA Evidence Based Committee and Advocacy Committee. Approximately 20 members of the two committees participated in the process. They submitted five items each from their practices and experience of tests or procedures that they found were commonly overutilized. The items were placed in order of number of times listed by each surgeon; a total of 30 items were submitted. The two committees then agreed on a final list of five procedures, based on frequency of responses and importance of the condition. After the list was reviewed and feedback provided, the POSNA board of directors voted on a final list. The AAP Executive Committee then provided final approval.
The committee noted that the list is provided for informational purposes and is not intended as a substitute for consultation with a physician.
Read the full list with more details here.
Trial shows ‘signals’ in favor of general anesthesia during EVT for stroke
The provision of general anesthesia during endovascular therapy for acute ischemic stroke patients with large-vessel occlusions did not result in more infarct growth when compared with conscious sedation in a new randomized trial, contrary to previous findings.
Furthermore, the single-center, open-label, blinded-endpoint General or Local Anesthesia in Intra Arterial Therapy (GOLIATH) trial also reported that patients randomized to the general anesthesia (GA) group had improved functional outcomes on the modified Rankin Scale at 90 days, with a 91% greater likelihood for lower scores than with conscious sedation (CS) (odds ratio, 1.91; 95% confidence interval, 1.03-3.56).
The GOLIATH trial randomized patients to general anesthetic (n = 65) or conscious sedation (n = 63). The average age of the patients was 71.4 years and 48.4% of the cohort were women. The patients’ median National Institutes of Health Stroke Scale score was 18 (interquartile range [IQR], 14-21), and the initial infarct size was also comparable between the GA and CS groups, respectively (median [interquartile range], 10.5 [2.4-23.6] mL vs. 13.3 [5.2-31.1] mL; P = .26)
The trial’s primary endpoint results showed that although final infarct volume was smaller in the GA group, the difference in the volume of infarct growth 48-72 hours after symptom onset among patients treated under GA or CS did not reach statistical significance (median [IQR] growth, 8.2 [2.2-38.6] mL vs. 19.4 [2.4-79.0] mL; P = .10).
“Assuming a normal distribution, the mean infarct growth for CS was 57.4 mL and for GA was 34.1 mL (difference, 23.2 mL; 95% CI, –6.4 to 52.9),” the research team noted.
A higher rate of successful reperfusion in the GA arm appeared to reflect its better clinical outcomes. Successful reperfusion occurred in 76.9% of GA patients, compared with 60.3% of CS patients (P = .04).
There were no clinically meaningful differences in safety endpoints between the two arms. Four patients (6.3%) in the CS group were converted to GA.
Significantly more patients in the GA group than in the CS group experienced a decrease of greater than 20% in mean arterial pressure (MAP) (87.7% vs. 34.9%; P = .001). However, when MAP dropped below 70 mm Hg, the duration was non-significantly longer for CS patients than for GA patients (6.5 [2-13] minutes vs. 2 [1-5.5] minutes; P = .09).
A longer delay from arrival at the neurointerventional suite to groin puncture was also seen for patients in the GA group. But the median difference of 9 minutes was “acceptable in the context of the much longer overall time from stroke onset to treatment and from stroke onset to reperfusion, which was not significantly different between the competing arms,” the authors said.
The authors said that overall their findings supported GA as a viable anesthetic approach during EVT. “Contrary to numerous nonrandomized studies that have reported better outcomes with CS, the GOLIATH trial shows signals in favor of GA for multiple endpoints,” the research team wrote. “Performing EVT under GA, compared with CS, does not result in worse tissue or clinical outcomes when using a GA protocol that limits the time delay for intubation (less than 10 minutes) and blood pressure level within recommended limits (systolic blood pressure greater than 140 mm Hg and MAP greater than 70 mm Hg).”
The trial was funded by Aarhus University Hospital. One author reported research grants from Penumbra and Neuravi, and another author reported a research grant from Health Research Fund of Central Denmark Region.
SOURCE: Simonsen C et al., JAMA Neurol. 2018 Jan 16. doi: 10.1001/jamaneurol.2017.4474
The provision of general anesthesia during endovascular therapy for acute ischemic stroke patients with large-vessel occlusions did not result in more infarct growth when compared with conscious sedation in a new randomized trial, contrary to previous findings.
Furthermore, the single-center, open-label, blinded-endpoint General or Local Anesthesia in Intra Arterial Therapy (GOLIATH) trial also reported that patients randomized to the general anesthesia (GA) group had improved functional outcomes on the modified Rankin Scale at 90 days, with a 91% greater likelihood for lower scores than with conscious sedation (CS) (odds ratio, 1.91; 95% confidence interval, 1.03-3.56).
The GOLIATH trial randomized patients to general anesthetic (n = 65) or conscious sedation (n = 63). The average age of the patients was 71.4 years and 48.4% of the cohort were women. The patients’ median National Institutes of Health Stroke Scale score was 18 (interquartile range [IQR], 14-21), and the initial infarct size was also comparable between the GA and CS groups, respectively (median [interquartile range], 10.5 [2.4-23.6] mL vs. 13.3 [5.2-31.1] mL; P = .26)
The trial’s primary endpoint results showed that although final infarct volume was smaller in the GA group, the difference in the volume of infarct growth 48-72 hours after symptom onset among patients treated under GA or CS did not reach statistical significance (median [IQR] growth, 8.2 [2.2-38.6] mL vs. 19.4 [2.4-79.0] mL; P = .10).
“Assuming a normal distribution, the mean infarct growth for CS was 57.4 mL and for GA was 34.1 mL (difference, 23.2 mL; 95% CI, –6.4 to 52.9),” the research team noted.
A higher rate of successful reperfusion in the GA arm appeared to reflect its better clinical outcomes. Successful reperfusion occurred in 76.9% of GA patients, compared with 60.3% of CS patients (P = .04).
There were no clinically meaningful differences in safety endpoints between the two arms. Four patients (6.3%) in the CS group were converted to GA.
Significantly more patients in the GA group than in the CS group experienced a decrease of greater than 20% in mean arterial pressure (MAP) (87.7% vs. 34.9%; P = .001). However, when MAP dropped below 70 mm Hg, the duration was non-significantly longer for CS patients than for GA patients (6.5 [2-13] minutes vs. 2 [1-5.5] minutes; P = .09).
A longer delay from arrival at the neurointerventional suite to groin puncture was also seen for patients in the GA group. But the median difference of 9 minutes was “acceptable in the context of the much longer overall time from stroke onset to treatment and from stroke onset to reperfusion, which was not significantly different between the competing arms,” the authors said.
The authors said that overall their findings supported GA as a viable anesthetic approach during EVT. “Contrary to numerous nonrandomized studies that have reported better outcomes with CS, the GOLIATH trial shows signals in favor of GA for multiple endpoints,” the research team wrote. “Performing EVT under GA, compared with CS, does not result in worse tissue or clinical outcomes when using a GA protocol that limits the time delay for intubation (less than 10 minutes) and blood pressure level within recommended limits (systolic blood pressure greater than 140 mm Hg and MAP greater than 70 mm Hg).”
The trial was funded by Aarhus University Hospital. One author reported research grants from Penumbra and Neuravi, and another author reported a research grant from Health Research Fund of Central Denmark Region.
SOURCE: Simonsen C et al., JAMA Neurol. 2018 Jan 16. doi: 10.1001/jamaneurol.2017.4474
The provision of general anesthesia during endovascular therapy for acute ischemic stroke patients with large-vessel occlusions did not result in more infarct growth when compared with conscious sedation in a new randomized trial, contrary to previous findings.
Furthermore, the single-center, open-label, blinded-endpoint General or Local Anesthesia in Intra Arterial Therapy (GOLIATH) trial also reported that patients randomized to the general anesthesia (GA) group had improved functional outcomes on the modified Rankin Scale at 90 days, with a 91% greater likelihood for lower scores than with conscious sedation (CS) (odds ratio, 1.91; 95% confidence interval, 1.03-3.56).
The GOLIATH trial randomized patients to general anesthetic (n = 65) or conscious sedation (n = 63). The average age of the patients was 71.4 years and 48.4% of the cohort were women. The patients’ median National Institutes of Health Stroke Scale score was 18 (interquartile range [IQR], 14-21), and the initial infarct size was also comparable between the GA and CS groups, respectively (median [interquartile range], 10.5 [2.4-23.6] mL vs. 13.3 [5.2-31.1] mL; P = .26)
The trial’s primary endpoint results showed that although final infarct volume was smaller in the GA group, the difference in the volume of infarct growth 48-72 hours after symptom onset among patients treated under GA or CS did not reach statistical significance (median [IQR] growth, 8.2 [2.2-38.6] mL vs. 19.4 [2.4-79.0] mL; P = .10).
“Assuming a normal distribution, the mean infarct growth for CS was 57.4 mL and for GA was 34.1 mL (difference, 23.2 mL; 95% CI, –6.4 to 52.9),” the research team noted.
A higher rate of successful reperfusion in the GA arm appeared to reflect its better clinical outcomes. Successful reperfusion occurred in 76.9% of GA patients, compared with 60.3% of CS patients (P = .04).
There were no clinically meaningful differences in safety endpoints between the two arms. Four patients (6.3%) in the CS group were converted to GA.
Significantly more patients in the GA group than in the CS group experienced a decrease of greater than 20% in mean arterial pressure (MAP) (87.7% vs. 34.9%; P = .001). However, when MAP dropped below 70 mm Hg, the duration was non-significantly longer for CS patients than for GA patients (6.5 [2-13] minutes vs. 2 [1-5.5] minutes; P = .09).
A longer delay from arrival at the neurointerventional suite to groin puncture was also seen for patients in the GA group. But the median difference of 9 minutes was “acceptable in the context of the much longer overall time from stroke onset to treatment and from stroke onset to reperfusion, which was not significantly different between the competing arms,” the authors said.
The authors said that overall their findings supported GA as a viable anesthetic approach during EVT. “Contrary to numerous nonrandomized studies that have reported better outcomes with CS, the GOLIATH trial shows signals in favor of GA for multiple endpoints,” the research team wrote. “Performing EVT under GA, compared with CS, does not result in worse tissue or clinical outcomes when using a GA protocol that limits the time delay for intubation (less than 10 minutes) and blood pressure level within recommended limits (systolic blood pressure greater than 140 mm Hg and MAP greater than 70 mm Hg).”
The trial was funded by Aarhus University Hospital. One author reported research grants from Penumbra and Neuravi, and another author reported a research grant from Health Research Fund of Central Denmark Region.
SOURCE: Simonsen C et al., JAMA Neurol. 2018 Jan 16. doi: 10.1001/jamaneurol.2017.4474
FROM JAMA NEUROLOGY
Key clinical point: A new trial shows signals in multiple endpoints in favor of general anesthesia for acute ischemic stroke patients with large-vessel occlusions who undergo endovascular therapy.
Major finding: The difference in the volume of infarct growth 48-72 hours after symptom onset among patients treated under general anesthesia or conscious sedation did not reach statistical significance (median [IQR] growth, 8.2 [2.2-38.6] mL vs. 19.4 [2.4-79.0] mL; P = .10).
Study details: The single-center, open-label, blinded-endpoint GOLIATH trial randomized 128 acute ischemic stroke patients to general anesthesia or conscious sedation.
Disclosures: The trial was funded by Aarhus University Hospital. One author reported research grants from Penumbra and Neuravi, and another author reported a research grant from Health Research Fund of Central Denmark Region.
Source: Simonsen C et al. JAMA Neurol. 2018 Jan 16. doi: 10.1001/jamaneurol.2017.4474.
Adding hypertension in pregnancy doesn’t refine ASCVD risk prediction tool
ANAHEIM, CALIF. – The first-ever study to examine the clinical utility of incorporating a history of hypertensive disorders of pregnancy into the American College of Cardiology/American Heart Association Atherosclerotic Cardiovascular Disease Risk Calculator in an effort to better delineate risk in women failed to show any added benefit.
But that doesn’t mean such a history is without value in daily clinical practice, Jennifer J. Stuart, ScD, asserted at the American Heart Association scientific sessions.
“While we did not demonstrate that hypertensive disorders of pregnancy improved cardiovascular risk discrimination in women, we do still believe – and I still believe – that hypertensive disorders of pregnancy remain an important risk marker for cardiovascular disease in women,” said Dr. Stuart of the Harvard School of Public Health, Boston.
“In this latest analysis we’ve demonstrated over a fourfold increased risk of chronic hypertension in these women in the first 5 years after delivery. So we do see increased risk very soon after delivery, and it persists for decades. And hypertensive disorders of pregnancy as a risk marker does offer practical advantages: ease of ascertainment, low cost, and availability earlier in life,” the researcher noted.
Her study hypothesis was that adding hypertensive disorders of pregnancy – that is, gestational hypertension and preeclampsia – and parity to the current ACC/AHA ASCVD Risk Calculator would enhance the tool’s predictive tool’s power in women.
“We wanted to know if a history of hypertensive disorders of pregnancy can be leveraged to capture women currently being missed in screening,” she explained.
Her expectation that this would be the case was based on solid evidence that hypertensive disorders of pregnancy, which occur in 10%-15% of all pregnancies, are associated with subsequent increased risk of cardiovascular events. For example, a meta-analysis of published studies involving nearly 3.5 million women, including almost 200,000 with a history of preeclampsia, showed that preeclampsia was associated with a 2.16-fold increased risk of ischemic heart disease during 11.7 years of follow-up (BMJ. 2007 Nov 10;335[7627]:974). This meta-analysis was among the evidence that persuaded the AHA in 2011 to formally add hypertensive disorders of pregnancy to the list of risk factors for cardiovascular disease in women (Circulation. 2011 Mar 22;123[11]:1243-62).
Dr. Stuart also incorporated parity in her investigational revised ASCVD risk model, because parity has been shown to be an independent risk factor of cardiovascular disease in a relationship described by a J-shaped curve.
She put the souped-up risk prediction model to the test by separately applying it and the current version to data from the longitudinal prospective Nurses’ Health Study II. For this analysis, nearly 68,000 female registered nurses were followed for new diseases every 2 years from 1989, when they were aged 25-42, through 2013. She and her coinvestigators applied the two 10-year risk-prediction models to the overall cohort and again separately to women at aged 40-49 and 50-59.
The bottom line: This might be because the nurses comprise a relatively low-risk population. Also, even though hypertensive disorders of pregnancy are associated with 10-year cardiovascular disease risk independent of the established risk factors, there may be enough overlap that the standard risk factors sufficiently capture the risk.
“It may be that the information on history of hypertensive disorders of pregnancy should be ascertained in the 20s and 30s, rather than waiting until age 40 or later, when we generally apply cardiovascular risk scores in practice. That [earlier assessment] may be a really important and valuable opportunity to identify these women at high risk and utilize primary prevention,” according to Dr. Stuart.
What’s next? “I’m certainly interested in educating these women about their increased risk. This is not something that’s done consistently across the country and across practices, and we really believe this is an important message for women to get when they deliver these pregnancies,” she added.
Dr. Stuart reported having no financial conflicts of interest regarding her study.
SOURCE: Stuart JJ. AHA Scientific Sessions.
ANAHEIM, CALIF. – The first-ever study to examine the clinical utility of incorporating a history of hypertensive disorders of pregnancy into the American College of Cardiology/American Heart Association Atherosclerotic Cardiovascular Disease Risk Calculator in an effort to better delineate risk in women failed to show any added benefit.
But that doesn’t mean such a history is without value in daily clinical practice, Jennifer J. Stuart, ScD, asserted at the American Heart Association scientific sessions.
“While we did not demonstrate that hypertensive disorders of pregnancy improved cardiovascular risk discrimination in women, we do still believe – and I still believe – that hypertensive disorders of pregnancy remain an important risk marker for cardiovascular disease in women,” said Dr. Stuart of the Harvard School of Public Health, Boston.
“In this latest analysis we’ve demonstrated over a fourfold increased risk of chronic hypertension in these women in the first 5 years after delivery. So we do see increased risk very soon after delivery, and it persists for decades. And hypertensive disorders of pregnancy as a risk marker does offer practical advantages: ease of ascertainment, low cost, and availability earlier in life,” the researcher noted.
Her study hypothesis was that adding hypertensive disorders of pregnancy – that is, gestational hypertension and preeclampsia – and parity to the current ACC/AHA ASCVD Risk Calculator would enhance the tool’s predictive tool’s power in women.
“We wanted to know if a history of hypertensive disorders of pregnancy can be leveraged to capture women currently being missed in screening,” she explained.
Her expectation that this would be the case was based on solid evidence that hypertensive disorders of pregnancy, which occur in 10%-15% of all pregnancies, are associated with subsequent increased risk of cardiovascular events. For example, a meta-analysis of published studies involving nearly 3.5 million women, including almost 200,000 with a history of preeclampsia, showed that preeclampsia was associated with a 2.16-fold increased risk of ischemic heart disease during 11.7 years of follow-up (BMJ. 2007 Nov 10;335[7627]:974). This meta-analysis was among the evidence that persuaded the AHA in 2011 to formally add hypertensive disorders of pregnancy to the list of risk factors for cardiovascular disease in women (Circulation. 2011 Mar 22;123[11]:1243-62).
Dr. Stuart also incorporated parity in her investigational revised ASCVD risk model, because parity has been shown to be an independent risk factor of cardiovascular disease in a relationship described by a J-shaped curve.
She put the souped-up risk prediction model to the test by separately applying it and the current version to data from the longitudinal prospective Nurses’ Health Study II. For this analysis, nearly 68,000 female registered nurses were followed for new diseases every 2 years from 1989, when they were aged 25-42, through 2013. She and her coinvestigators applied the two 10-year risk-prediction models to the overall cohort and again separately to women at aged 40-49 and 50-59.
The bottom line: This might be because the nurses comprise a relatively low-risk population. Also, even though hypertensive disorders of pregnancy are associated with 10-year cardiovascular disease risk independent of the established risk factors, there may be enough overlap that the standard risk factors sufficiently capture the risk.
“It may be that the information on history of hypertensive disorders of pregnancy should be ascertained in the 20s and 30s, rather than waiting until age 40 or later, when we generally apply cardiovascular risk scores in practice. That [earlier assessment] may be a really important and valuable opportunity to identify these women at high risk and utilize primary prevention,” according to Dr. Stuart.
What’s next? “I’m certainly interested in educating these women about their increased risk. This is not something that’s done consistently across the country and across practices, and we really believe this is an important message for women to get when they deliver these pregnancies,” she added.
Dr. Stuart reported having no financial conflicts of interest regarding her study.
SOURCE: Stuart JJ. AHA Scientific Sessions.
ANAHEIM, CALIF. – The first-ever study to examine the clinical utility of incorporating a history of hypertensive disorders of pregnancy into the American College of Cardiology/American Heart Association Atherosclerotic Cardiovascular Disease Risk Calculator in an effort to better delineate risk in women failed to show any added benefit.
But that doesn’t mean such a history is without value in daily clinical practice, Jennifer J. Stuart, ScD, asserted at the American Heart Association scientific sessions.
“While we did not demonstrate that hypertensive disorders of pregnancy improved cardiovascular risk discrimination in women, we do still believe – and I still believe – that hypertensive disorders of pregnancy remain an important risk marker for cardiovascular disease in women,” said Dr. Stuart of the Harvard School of Public Health, Boston.
“In this latest analysis we’ve demonstrated over a fourfold increased risk of chronic hypertension in these women in the first 5 years after delivery. So we do see increased risk very soon after delivery, and it persists for decades. And hypertensive disorders of pregnancy as a risk marker does offer practical advantages: ease of ascertainment, low cost, and availability earlier in life,” the researcher noted.
Her study hypothesis was that adding hypertensive disorders of pregnancy – that is, gestational hypertension and preeclampsia – and parity to the current ACC/AHA ASCVD Risk Calculator would enhance the tool’s predictive tool’s power in women.
“We wanted to know if a history of hypertensive disorders of pregnancy can be leveraged to capture women currently being missed in screening,” she explained.
Her expectation that this would be the case was based on solid evidence that hypertensive disorders of pregnancy, which occur in 10%-15% of all pregnancies, are associated with subsequent increased risk of cardiovascular events. For example, a meta-analysis of published studies involving nearly 3.5 million women, including almost 200,000 with a history of preeclampsia, showed that preeclampsia was associated with a 2.16-fold increased risk of ischemic heart disease during 11.7 years of follow-up (BMJ. 2007 Nov 10;335[7627]:974). This meta-analysis was among the evidence that persuaded the AHA in 2011 to formally add hypertensive disorders of pregnancy to the list of risk factors for cardiovascular disease in women (Circulation. 2011 Mar 22;123[11]:1243-62).
Dr. Stuart also incorporated parity in her investigational revised ASCVD risk model, because parity has been shown to be an independent risk factor of cardiovascular disease in a relationship described by a J-shaped curve.
She put the souped-up risk prediction model to the test by separately applying it and the current version to data from the longitudinal prospective Nurses’ Health Study II. For this analysis, nearly 68,000 female registered nurses were followed for new diseases every 2 years from 1989, when they were aged 25-42, through 2013. She and her coinvestigators applied the two 10-year risk-prediction models to the overall cohort and again separately to women at aged 40-49 and 50-59.
The bottom line: This might be because the nurses comprise a relatively low-risk population. Also, even though hypertensive disorders of pregnancy are associated with 10-year cardiovascular disease risk independent of the established risk factors, there may be enough overlap that the standard risk factors sufficiently capture the risk.
“It may be that the information on history of hypertensive disorders of pregnancy should be ascertained in the 20s and 30s, rather than waiting until age 40 or later, when we generally apply cardiovascular risk scores in practice. That [earlier assessment] may be a really important and valuable opportunity to identify these women at high risk and utilize primary prevention,” according to Dr. Stuart.
What’s next? “I’m certainly interested in educating these women about their increased risk. This is not something that’s done consistently across the country and across practices, and we really believe this is an important message for women to get when they deliver these pregnancies,” she added.
Dr. Stuart reported having no financial conflicts of interest regarding her study.
SOURCE: Stuart JJ. AHA Scientific Sessions.
REPORTING FROM THE AHA SCIENTIFIC SESSIONS
Key clinical point: The ACC/AHA Atherosclerotic Cardiovascular Disease Risk Calculator doesn’t do a better job of predicting 10-year risk in women when a history of hypertensive disorders of pregnancy is added into the formula.
Major finding: Incorporating a woman’s history of hypertensive disorders of pregnancy into the Atherosclerotic Cardiovascular Disease Risk Calculator doesn’t improve the tool’s accuracy in predicting 10-year risk.
Study details: An analysis of data from the longitudinal, prospective Nurses’ Health Study II.
Disclosures: The study presenter reported having no financial conflicts of interest.
Source: Stuart JJ. AHA Scientific Sessions.
Study finds AD accounts for hundreds of thousands of annual ED visits
SAN DIEGO – A new study finds that primary diagnoses of atopic dermatitis (AD) are made hundreds of thousands of times in United States emergency departments each year.
The numbers appear to be rising along with costs, researchers reported, and there are signs of disparities, with poorer people more likely to have an ED visit with a primary diagnosis of AD. The study was presented in a poster at the annual meeting of the American Academy of Dermatology.
He and his coauthor, Lauren Kwa, also with the department of dermatology at Northwestern, conducted the analysis to better understand the role of AD in emergency care. “Many AD patients experience severe, unpredictable flares and worsening chronic disease that warrant urgent treatment,” Dr. Silverberg said. “However, patients typically don’t have instant access to outpatient dermatological care and may be forced to turn to the urgent care setting.”
Indeed, he noted, “previous U.S. population–based studies showed that people with AD have higher odds of [ED] utilization than the rest of the population.”
He and Ms. Kwa examined 2006-2012 data from the Nationwide Emergency Department Sample, which includes information on about 20% of all emergency visits in the United States.
During that period, there were 1.86 million ED visits with a primary diagnosis of AD. The annual weighted prevalence of primary diagnoses of AD stayed fairly stable through the period, ranging from 2,589 to 2,769 per 1 million visits. However, the weighted prevalence of secondary AD diagnoses grew steadily from 1,227 per 1 million visits in 2006 to 1,533 per 1 million visits in 2012.
The researchers estimated that the total cost of annual costs of AD-related ED visits grew from $86.9 million in 2006 to $172.8 million in 2012 (P less than .05).
The study also linked primary diagnoses of AD to having Medicaid insurance or being uninsured, being poorer, or visiting hospitals in “micropolitan” areas (small urban communities such as Bozeman, Mont., and Durango, Colo.).
The study did not examine what medications were prescribed in the ED. However, Dr. Silverberg said, “my anecdotal experience has been that many AD patients are prescribed systemic steroids by nondermatologists in the [ED] setting. While these are rapidly effective, they typically have short-lived efficacy and result in rebound flares upon cessation. Patients are rarely counseled on appropriate skin care techniques or given long-term treatment approaches in the [ED] setting, which fails to achieve adequate long-term disease control.”
What’s next? “We are now studying how AD severity, disease course, and treatment impact [ED] utilization for AD,” Dr. Silverberg said.
No specific study funding was reported. He and Ms. Kwa report no relevant disclosures.
SOURCE: Silverberg, J et al. Poster 7021.
SAN DIEGO – A new study finds that primary diagnoses of atopic dermatitis (AD) are made hundreds of thousands of times in United States emergency departments each year.
The numbers appear to be rising along with costs, researchers reported, and there are signs of disparities, with poorer people more likely to have an ED visit with a primary diagnosis of AD. The study was presented in a poster at the annual meeting of the American Academy of Dermatology.
He and his coauthor, Lauren Kwa, also with the department of dermatology at Northwestern, conducted the analysis to better understand the role of AD in emergency care. “Many AD patients experience severe, unpredictable flares and worsening chronic disease that warrant urgent treatment,” Dr. Silverberg said. “However, patients typically don’t have instant access to outpatient dermatological care and may be forced to turn to the urgent care setting.”
Indeed, he noted, “previous U.S. population–based studies showed that people with AD have higher odds of [ED] utilization than the rest of the population.”
He and Ms. Kwa examined 2006-2012 data from the Nationwide Emergency Department Sample, which includes information on about 20% of all emergency visits in the United States.
During that period, there were 1.86 million ED visits with a primary diagnosis of AD. The annual weighted prevalence of primary diagnoses of AD stayed fairly stable through the period, ranging from 2,589 to 2,769 per 1 million visits. However, the weighted prevalence of secondary AD diagnoses grew steadily from 1,227 per 1 million visits in 2006 to 1,533 per 1 million visits in 2012.
The researchers estimated that the total cost of annual costs of AD-related ED visits grew from $86.9 million in 2006 to $172.8 million in 2012 (P less than .05).
The study also linked primary diagnoses of AD to having Medicaid insurance or being uninsured, being poorer, or visiting hospitals in “micropolitan” areas (small urban communities such as Bozeman, Mont., and Durango, Colo.).
The study did not examine what medications were prescribed in the ED. However, Dr. Silverberg said, “my anecdotal experience has been that many AD patients are prescribed systemic steroids by nondermatologists in the [ED] setting. While these are rapidly effective, they typically have short-lived efficacy and result in rebound flares upon cessation. Patients are rarely counseled on appropriate skin care techniques or given long-term treatment approaches in the [ED] setting, which fails to achieve adequate long-term disease control.”
What’s next? “We are now studying how AD severity, disease course, and treatment impact [ED] utilization for AD,” Dr. Silverberg said.
No specific study funding was reported. He and Ms. Kwa report no relevant disclosures.
SOURCE: Silverberg, J et al. Poster 7021.
SAN DIEGO – A new study finds that primary diagnoses of atopic dermatitis (AD) are made hundreds of thousands of times in United States emergency departments each year.
The numbers appear to be rising along with costs, researchers reported, and there are signs of disparities, with poorer people more likely to have an ED visit with a primary diagnosis of AD. The study was presented in a poster at the annual meeting of the American Academy of Dermatology.
He and his coauthor, Lauren Kwa, also with the department of dermatology at Northwestern, conducted the analysis to better understand the role of AD in emergency care. “Many AD patients experience severe, unpredictable flares and worsening chronic disease that warrant urgent treatment,” Dr. Silverberg said. “However, patients typically don’t have instant access to outpatient dermatological care and may be forced to turn to the urgent care setting.”
Indeed, he noted, “previous U.S. population–based studies showed that people with AD have higher odds of [ED] utilization than the rest of the population.”
He and Ms. Kwa examined 2006-2012 data from the Nationwide Emergency Department Sample, which includes information on about 20% of all emergency visits in the United States.
During that period, there were 1.86 million ED visits with a primary diagnosis of AD. The annual weighted prevalence of primary diagnoses of AD stayed fairly stable through the period, ranging from 2,589 to 2,769 per 1 million visits. However, the weighted prevalence of secondary AD diagnoses grew steadily from 1,227 per 1 million visits in 2006 to 1,533 per 1 million visits in 2012.
The researchers estimated that the total cost of annual costs of AD-related ED visits grew from $86.9 million in 2006 to $172.8 million in 2012 (P less than .05).
The study also linked primary diagnoses of AD to having Medicaid insurance or being uninsured, being poorer, or visiting hospitals in “micropolitan” areas (small urban communities such as Bozeman, Mont., and Durango, Colo.).
The study did not examine what medications were prescribed in the ED. However, Dr. Silverberg said, “my anecdotal experience has been that many AD patients are prescribed systemic steroids by nondermatologists in the [ED] setting. While these are rapidly effective, they typically have short-lived efficacy and result in rebound flares upon cessation. Patients are rarely counseled on appropriate skin care techniques or given long-term treatment approaches in the [ED] setting, which fails to achieve adequate long-term disease control.”
What’s next? “We are now studying how AD severity, disease course, and treatment impact [ED] utilization for AD,” Dr. Silverberg said.
No specific study funding was reported. He and Ms. Kwa report no relevant disclosures.
SOURCE: Silverberg, J et al. Poster 7021.
REPORTING FROM AAD 18
Key clinical point: ED visits for atopic dermatitis are common, and their numbers are growing.
Major finding: An estimated 1.86 million ED visits in the United States from 2006 to 2012 were linked to a primary diagnosis of AD.
Study details: Analysis of data from the Nationwide Emergency Department Sample for 2006-2016.
Disclosures: No study funding was reported. The authors had no relevant disclosures.
Source: Silverberg J et al. Poster 7021.
Mast cell synovitis: potential target in RA?
MAUI, HAWAII – Could mast cell-rich synovitis become a novel target in patients with early rheumatoid arthritis?
Investigators at the University of London believe so. In a small but provocative study presented at the 2017 annual meeting of the American College of Rheumatology, they demonstrated that these mast cells are not an innocent bystander in joint inflammation; rather, they play an active albeit still incompletely understood role in the synovial inflammatory infiltrate and in disease progression, Orrin M. Troum, MD, said at the 2018 Rheumatology Winter Clinical Symposium.
Treatment with synthetic DMARDs was partially effective, both clinically and at the cellular level. Mean mast cell density fell from 14.2/mm2 at baseline to 8.2/mm2 at 6 months. But synovial mast cells were still present at 6 months in 9 of 20 patients. Those nine patients had significantly higher DAS28 scores – a mean of 4.08 versus 2.41 in the synovial mast cell–negative group – as well as higher synovitis scores. Disease remission as defined by a DAS28 score below 2.6 was achieved in only 2 of 9 patients with persistent mast cell-rich synovitis, as compared with 8 of 11 mast cell-negative patients.
Moreover, four of the nine patients with persistent mast cell-rich synovitis after 6 months of synthetic DMARDs had synovial lymphoid aggregates of CD20-positive B cells and/or CD138-positive plasma cells; in contrast, none of the 11 synovial mast cell-negative patients did, noted Dr. Troum, a rheumatologist at the University of Southern California, Los Angeles, who is in private practice in Santa Monica, Calif.
In theory, if a baseline synovial tissue immune cell profile could be identified that’s predictive of high-level responsiveness to synthetic DMARDs or, conversely, nonresponsiveness, tissue specimens could be used to stratify patients with early RA to different initial treatment strategies. The problem with that is few rheumatologists in the United States – and indeed worldwide – are proficient at performing ultrasound-guided synovial biopsies, according to Dr. Troum.
His description of the London study prompted a question as to whether any of the biologics used in rheumatology can inhibit mast cells. Arthur Kavanaugh, MD, symposium director, said the only agent that comes to mind is imatinib (Gleevec), a tyrosine kinase inhibitor used in the treatment of aggressive systemic mastocytosis as well as for certain leukemias.
“It has a ton of toxicity, though,” said Dr. Kavanaugh, professor of medicine and director of the Center for Innovative Therapy in the division of rheumatology, allergy, and immunology at the University of California, San Diego.
Dr. Troum reported having no financial conflicts regarding his presentation.
MAUI, HAWAII – Could mast cell-rich synovitis become a novel target in patients with early rheumatoid arthritis?
Investigators at the University of London believe so. In a small but provocative study presented at the 2017 annual meeting of the American College of Rheumatology, they demonstrated that these mast cells are not an innocent bystander in joint inflammation; rather, they play an active albeit still incompletely understood role in the synovial inflammatory infiltrate and in disease progression, Orrin M. Troum, MD, said at the 2018 Rheumatology Winter Clinical Symposium.
Treatment with synthetic DMARDs was partially effective, both clinically and at the cellular level. Mean mast cell density fell from 14.2/mm2 at baseline to 8.2/mm2 at 6 months. But synovial mast cells were still present at 6 months in 9 of 20 patients. Those nine patients had significantly higher DAS28 scores – a mean of 4.08 versus 2.41 in the synovial mast cell–negative group – as well as higher synovitis scores. Disease remission as defined by a DAS28 score below 2.6 was achieved in only 2 of 9 patients with persistent mast cell-rich synovitis, as compared with 8 of 11 mast cell-negative patients.
Moreover, four of the nine patients with persistent mast cell-rich synovitis after 6 months of synthetic DMARDs had synovial lymphoid aggregates of CD20-positive B cells and/or CD138-positive plasma cells; in contrast, none of the 11 synovial mast cell-negative patients did, noted Dr. Troum, a rheumatologist at the University of Southern California, Los Angeles, who is in private practice in Santa Monica, Calif.
In theory, if a baseline synovial tissue immune cell profile could be identified that’s predictive of high-level responsiveness to synthetic DMARDs or, conversely, nonresponsiveness, tissue specimens could be used to stratify patients with early RA to different initial treatment strategies. The problem with that is few rheumatologists in the United States – and indeed worldwide – are proficient at performing ultrasound-guided synovial biopsies, according to Dr. Troum.
His description of the London study prompted a question as to whether any of the biologics used in rheumatology can inhibit mast cells. Arthur Kavanaugh, MD, symposium director, said the only agent that comes to mind is imatinib (Gleevec), a tyrosine kinase inhibitor used in the treatment of aggressive systemic mastocytosis as well as for certain leukemias.
“It has a ton of toxicity, though,” said Dr. Kavanaugh, professor of medicine and director of the Center for Innovative Therapy in the division of rheumatology, allergy, and immunology at the University of California, San Diego.
Dr. Troum reported having no financial conflicts regarding his presentation.
MAUI, HAWAII – Could mast cell-rich synovitis become a novel target in patients with early rheumatoid arthritis?
Investigators at the University of London believe so. In a small but provocative study presented at the 2017 annual meeting of the American College of Rheumatology, they demonstrated that these mast cells are not an innocent bystander in joint inflammation; rather, they play an active albeit still incompletely understood role in the synovial inflammatory infiltrate and in disease progression, Orrin M. Troum, MD, said at the 2018 Rheumatology Winter Clinical Symposium.
Treatment with synthetic DMARDs was partially effective, both clinically and at the cellular level. Mean mast cell density fell from 14.2/mm2 at baseline to 8.2/mm2 at 6 months. But synovial mast cells were still present at 6 months in 9 of 20 patients. Those nine patients had significantly higher DAS28 scores – a mean of 4.08 versus 2.41 in the synovial mast cell–negative group – as well as higher synovitis scores. Disease remission as defined by a DAS28 score below 2.6 was achieved in only 2 of 9 patients with persistent mast cell-rich synovitis, as compared with 8 of 11 mast cell-negative patients.
Moreover, four of the nine patients with persistent mast cell-rich synovitis after 6 months of synthetic DMARDs had synovial lymphoid aggregates of CD20-positive B cells and/or CD138-positive plasma cells; in contrast, none of the 11 synovial mast cell-negative patients did, noted Dr. Troum, a rheumatologist at the University of Southern California, Los Angeles, who is in private practice in Santa Monica, Calif.
In theory, if a baseline synovial tissue immune cell profile could be identified that’s predictive of high-level responsiveness to synthetic DMARDs or, conversely, nonresponsiveness, tissue specimens could be used to stratify patients with early RA to different initial treatment strategies. The problem with that is few rheumatologists in the United States – and indeed worldwide – are proficient at performing ultrasound-guided synovial biopsies, according to Dr. Troum.
His description of the London study prompted a question as to whether any of the biologics used in rheumatology can inhibit mast cells. Arthur Kavanaugh, MD, symposium director, said the only agent that comes to mind is imatinib (Gleevec), a tyrosine kinase inhibitor used in the treatment of aggressive systemic mastocytosis as well as for certain leukemias.
“It has a ton of toxicity, though,” said Dr. Kavanaugh, professor of medicine and director of the Center for Innovative Therapy in the division of rheumatology, allergy, and immunology at the University of California, San Diego.
Dr. Troum reported having no financial conflicts regarding his presentation.
EXPERT ANALYSIS FROM RWCS 2018
Collaboration, consultation part of AAP teen depression guidelines update
The updated information includes recommendations on collaborative care, practice preparation, establishing networks of referrals, and much more.
“These guidelines were developed for PC clinicians who are in a position to identify and assist youth with depression in their practice settings,” they said. The guidelines apply to individuals aged 10-21 years, and support universal depression screening for those aged 12 and older.
Known as the Guidelines for Adolescent Depression in Primary Care (GLAD-PC), they consist of two parts: Practice Preparation, Identification, Assessment, and Initial Management, with Dr. Zuckerbrot as the lead author, and Treatment and Ongoing Management, led by Amy H. Cheung, MD, of the University of Toronto. They were published online in Pediatrics.
“It has been over 10 years since the [last] guidelines were published and they are supposed to be updated every 5,” Dr. Zuckerbrot said in an interview. “Given the new evidence on screening, psychopharmacology, and collaborative care, the guidelines needed to be revised. The USPSTF [United States Preventive Services Task Force ] and the AAP had already supported universal adolescent depression screening, and these guidelines are finally aligned with those positions.
“Different parts of the guidelines will be the go-to for different pediatricians, depending on where they are in their delivery of mental health care,” she explained. “Some may need help with practice preparation while others may need advice on screening; others may already be prescribing and may need advice on ongoing treatment and follow-up. I think there is something for everyone.”
Implementation of the guidelines is difficult in a short visit, Dr. Zuckerbrot acknowledged. “In addition, pediatricians may not have been well trained in the management of adolescent depression during their residencies.” However, the guidelines discuss both “real teams to support the pediatricians in their efforts, as well as virtual teams when staffing is limited.
“The guidelines advise that pediatricians learn about child psychiatry primary care consultation programs in their state and make use of those free telephone consultation programs.” The guidelines also discuss strategies for collaborative or integrative care, she said.
Part I
Part I of the guidelines, “Practice Preparation, Identification, Assessment, and Initial Management,” includes several recommendations for each topic.
For practice preparation, the guidelines recommend that clinicians seek training in the assessment, diagnosis, and treatment of depression, and that they establish a network of referrals and mental health resources in their communities. This network may include not only health professionals, but also current patients and families who are managing teen depression. If available, state-wide or regional child and adolescent psychiatry consultation programs can be included.
The identification and surveillance section of the guidelines calls for screening all patients aged 12 years and older for depression each year, using a formal screening tool on paper or online. The screening could occur at an annual wellness visit or any other medical visit, such as a sports physical. A second recommendation calls for identifying patients at increased risk for depression because of factors such as personal history, family history, substance use, other psychiatric disorders, frequent somatic complaints, or trauma, and monitoring these individuals regularly for signs of depression using a formal screening tool.
The assessment and diagnosis section states that assessment should include interviews with the patients alone as well as with their families or caregivers, and should include screening teens for functional impairment.
Primary care physicians should evaluate for depression not only if an adolescent tests positive on a screening tool, but also in children who present with any emotional problem as the chief complaint, and in those in whom depression is highly suspected even if they test negative on a formal screening tool, the guidelines state.
The three recommendations for initial management of depression in the primary care setting are educating patients and families about depression; developing a treatment plan (if the primary care clinician has had appropriate training) and setting specific treatment goals in areas of functioning such as at home, with peers, and at school; and developing a safety plan that includes restricting access to weapons or other means of self-harm, according to the guidelines.
Part II
Part II of the recommendations, “Treatment and Ongoing Management,” discusses options for managing depression in the primary care setting and utilizing outside resources.
The treatment recommendations emphasize the use of integrated models, if possible. “There is a growing recognition that complex chronic conditions, such as depression, are most successfully managed with proactive, multidisciplinary, patient-centered care teams,” Dr. Cheung and her associates said.
The recommendation for cases of mild depression calls for a period of “active support and monitoring” for 6-8 weeks before reassessing if the teen shows no improvement. By contrast, for cases of moderate to severe depression or cases with evidence of substance abuse or other psychoses, the recommendation calls for potential consultation with a mental health specialist and a discussion of the roles primary and specialty care will play in treatment. The guidelines include a flow chart for PC physicians to follow.
The guidelines suggest that PC clinicians recommend “scientifically tested and proven treatments,” such as psychotherapies, cognitive behavioral therapy (CBT) or interpersonal psychotherapy for adolescents, and/or antidepressant treatment, such as SSRIs, whenever possible and appropriate. It is important to monitor teens on antidepressants regularly to identify adverse events.
Recommendations for the ongoing management of teens with depression in the primary care setting include regular tracking of progress, reassessment if the teen shows no improvement in 6-8 weeks, and consultation with a mental health professional for those who show only partial improvement after exhausting primary care diagnostic and treatment options. Assessment of depressive symptoms is not the only thing to track. Functioning at home, school, and among peers also is important.
The final treatment recommendation is for active support of a depressed teen’s referral to mental health if necessary for best management and sharing care if possible, with an understanding of the roles of the primary and specialty clinicians, the guidelines state.
The guidelines project was funded by the Resource for Advancing Children’s Health Institute and the Bell Canada Chair in Adolescent Mood and Anxiety Disorders.
Dr. Cheung and Dr. Zuckerbrot receive book royalties. Dr Zuckerbrot works for child and adolescent psychiatry for primary care (CAP-PC), now a regional provider for Project TEACH in New York State, and she is on the steering committee as well as faculty for the REACH Institute; both of these institutions are described in the guidelines. Peter S. Jensen, MD, has received royalties from Random House, Oxford University Press, and APPI Inc. He is a part owner of a consulting company, CATCH Services LLC. He is the chief executive officer and president of a nonprofit organization, the Resource for Advancing Children’s Health Institute, but receives no compensation. The other authors indicated they have no financial relationships relevant to the guidelines.
“Mental health disorders have become one of the new morbidities in pediatric care,” Karalyn Kinsella, MD, said in an interview. “With one in five patients having depression, it is an illness that must be within our domain to identify and treat. I think the guidelines will make providers feel more confident in making a diagnosis and providing initial treatment. For those that do not feel comfortable, hopefully the guidelines will encourage them to seek training.
The take-home message for general pediatricians is that a standardized screening tool makes identifying depression relatively easy. “We have been using the PHQ-9 [Patient Health Questionnaire-9] in my office for several years, and it is very easy to administer and score, and is billable,” said Dr. Kinsella. “It can take some practice to tease out some typical teen behaviors, especially on the sleep and fatigue questions, but it provides an opportunity to open up discussion with the teen.
“Treatment [of depression] can be more complicated and time consuming, but rewarding and invaluable to the patient,” she emphasized. “Many states now have psychiatrists available by phone consultation to aid in management of medication. The key is establishing a list of quality counselors for referrals. With those supports and frequent follow-up, pediatricians can play a key role in the treatment of this prevalent and important illness that affects our patients.”
Dr. Kinsella is a pediatrician in Cheshire, Conn., and a member of the Pediatric News editorial advisory board. She was asked to comment on the new AAP teen depression guidelines.
“Mental health disorders have become one of the new morbidities in pediatric care,” Karalyn Kinsella, MD, said in an interview. “With one in five patients having depression, it is an illness that must be within our domain to identify and treat. I think the guidelines will make providers feel more confident in making a diagnosis and providing initial treatment. For those that do not feel comfortable, hopefully the guidelines will encourage them to seek training.
The take-home message for general pediatricians is that a standardized screening tool makes identifying depression relatively easy. “We have been using the PHQ-9 [Patient Health Questionnaire-9] in my office for several years, and it is very easy to administer and score, and is billable,” said Dr. Kinsella. “It can take some practice to tease out some typical teen behaviors, especially on the sleep and fatigue questions, but it provides an opportunity to open up discussion with the teen.
“Treatment [of depression] can be more complicated and time consuming, but rewarding and invaluable to the patient,” she emphasized. “Many states now have psychiatrists available by phone consultation to aid in management of medication. The key is establishing a list of quality counselors for referrals. With those supports and frequent follow-up, pediatricians can play a key role in the treatment of this prevalent and important illness that affects our patients.”
Dr. Kinsella is a pediatrician in Cheshire, Conn., and a member of the Pediatric News editorial advisory board. She was asked to comment on the new AAP teen depression guidelines.
“Mental health disorders have become one of the new morbidities in pediatric care,” Karalyn Kinsella, MD, said in an interview. “With one in five patients having depression, it is an illness that must be within our domain to identify and treat. I think the guidelines will make providers feel more confident in making a diagnosis and providing initial treatment. For those that do not feel comfortable, hopefully the guidelines will encourage them to seek training.
The take-home message for general pediatricians is that a standardized screening tool makes identifying depression relatively easy. “We have been using the PHQ-9 [Patient Health Questionnaire-9] in my office for several years, and it is very easy to administer and score, and is billable,” said Dr. Kinsella. “It can take some practice to tease out some typical teen behaviors, especially on the sleep and fatigue questions, but it provides an opportunity to open up discussion with the teen.
“Treatment [of depression] can be more complicated and time consuming, but rewarding and invaluable to the patient,” she emphasized. “Many states now have psychiatrists available by phone consultation to aid in management of medication. The key is establishing a list of quality counselors for referrals. With those supports and frequent follow-up, pediatricians can play a key role in the treatment of this prevalent and important illness that affects our patients.”
Dr. Kinsella is a pediatrician in Cheshire, Conn., and a member of the Pediatric News editorial advisory board. She was asked to comment on the new AAP teen depression guidelines.
The updated information includes recommendations on collaborative care, practice preparation, establishing networks of referrals, and much more.
“These guidelines were developed for PC clinicians who are in a position to identify and assist youth with depression in their practice settings,” they said. The guidelines apply to individuals aged 10-21 years, and support universal depression screening for those aged 12 and older.
Known as the Guidelines for Adolescent Depression in Primary Care (GLAD-PC), they consist of two parts: Practice Preparation, Identification, Assessment, and Initial Management, with Dr. Zuckerbrot as the lead author, and Treatment and Ongoing Management, led by Amy H. Cheung, MD, of the University of Toronto. They were published online in Pediatrics.
“It has been over 10 years since the [last] guidelines were published and they are supposed to be updated every 5,” Dr. Zuckerbrot said in an interview. “Given the new evidence on screening, psychopharmacology, and collaborative care, the guidelines needed to be revised. The USPSTF [United States Preventive Services Task Force ] and the AAP had already supported universal adolescent depression screening, and these guidelines are finally aligned with those positions.
“Different parts of the guidelines will be the go-to for different pediatricians, depending on where they are in their delivery of mental health care,” she explained. “Some may need help with practice preparation while others may need advice on screening; others may already be prescribing and may need advice on ongoing treatment and follow-up. I think there is something for everyone.”
Implementation of the guidelines is difficult in a short visit, Dr. Zuckerbrot acknowledged. “In addition, pediatricians may not have been well trained in the management of adolescent depression during their residencies.” However, the guidelines discuss both “real teams to support the pediatricians in their efforts, as well as virtual teams when staffing is limited.
“The guidelines advise that pediatricians learn about child psychiatry primary care consultation programs in their state and make use of those free telephone consultation programs.” The guidelines also discuss strategies for collaborative or integrative care, she said.
Part I
Part I of the guidelines, “Practice Preparation, Identification, Assessment, and Initial Management,” includes several recommendations for each topic.
For practice preparation, the guidelines recommend that clinicians seek training in the assessment, diagnosis, and treatment of depression, and that they establish a network of referrals and mental health resources in their communities. This network may include not only health professionals, but also current patients and families who are managing teen depression. If available, state-wide or regional child and adolescent psychiatry consultation programs can be included.
The identification and surveillance section of the guidelines calls for screening all patients aged 12 years and older for depression each year, using a formal screening tool on paper or online. The screening could occur at an annual wellness visit or any other medical visit, such as a sports physical. A second recommendation calls for identifying patients at increased risk for depression because of factors such as personal history, family history, substance use, other psychiatric disorders, frequent somatic complaints, or trauma, and monitoring these individuals regularly for signs of depression using a formal screening tool.
The assessment and diagnosis section states that assessment should include interviews with the patients alone as well as with their families or caregivers, and should include screening teens for functional impairment.
Primary care physicians should evaluate for depression not only if an adolescent tests positive on a screening tool, but also in children who present with any emotional problem as the chief complaint, and in those in whom depression is highly suspected even if they test negative on a formal screening tool, the guidelines state.
The three recommendations for initial management of depression in the primary care setting are educating patients and families about depression; developing a treatment plan (if the primary care clinician has had appropriate training) and setting specific treatment goals in areas of functioning such as at home, with peers, and at school; and developing a safety plan that includes restricting access to weapons or other means of self-harm, according to the guidelines.
Part II
Part II of the recommendations, “Treatment and Ongoing Management,” discusses options for managing depression in the primary care setting and utilizing outside resources.
The treatment recommendations emphasize the use of integrated models, if possible. “There is a growing recognition that complex chronic conditions, such as depression, are most successfully managed with proactive, multidisciplinary, patient-centered care teams,” Dr. Cheung and her associates said.
The recommendation for cases of mild depression calls for a period of “active support and monitoring” for 6-8 weeks before reassessing if the teen shows no improvement. By contrast, for cases of moderate to severe depression or cases with evidence of substance abuse or other psychoses, the recommendation calls for potential consultation with a mental health specialist and a discussion of the roles primary and specialty care will play in treatment. The guidelines include a flow chart for PC physicians to follow.
The guidelines suggest that PC clinicians recommend “scientifically tested and proven treatments,” such as psychotherapies, cognitive behavioral therapy (CBT) or interpersonal psychotherapy for adolescents, and/or antidepressant treatment, such as SSRIs, whenever possible and appropriate. It is important to monitor teens on antidepressants regularly to identify adverse events.
Recommendations for the ongoing management of teens with depression in the primary care setting include regular tracking of progress, reassessment if the teen shows no improvement in 6-8 weeks, and consultation with a mental health professional for those who show only partial improvement after exhausting primary care diagnostic and treatment options. Assessment of depressive symptoms is not the only thing to track. Functioning at home, school, and among peers also is important.
The final treatment recommendation is for active support of a depressed teen’s referral to mental health if necessary for best management and sharing care if possible, with an understanding of the roles of the primary and specialty clinicians, the guidelines state.
The guidelines project was funded by the Resource for Advancing Children’s Health Institute and the Bell Canada Chair in Adolescent Mood and Anxiety Disorders.
Dr. Cheung and Dr. Zuckerbrot receive book royalties. Dr Zuckerbrot works for child and adolescent psychiatry for primary care (CAP-PC), now a regional provider for Project TEACH in New York State, and she is on the steering committee as well as faculty for the REACH Institute; both of these institutions are described in the guidelines. Peter S. Jensen, MD, has received royalties from Random House, Oxford University Press, and APPI Inc. He is a part owner of a consulting company, CATCH Services LLC. He is the chief executive officer and president of a nonprofit organization, the Resource for Advancing Children’s Health Institute, but receives no compensation. The other authors indicated they have no financial relationships relevant to the guidelines.
The updated information includes recommendations on collaborative care, practice preparation, establishing networks of referrals, and much more.
“These guidelines were developed for PC clinicians who are in a position to identify and assist youth with depression in their practice settings,” they said. The guidelines apply to individuals aged 10-21 years, and support universal depression screening for those aged 12 and older.
Known as the Guidelines for Adolescent Depression in Primary Care (GLAD-PC), they consist of two parts: Practice Preparation, Identification, Assessment, and Initial Management, with Dr. Zuckerbrot as the lead author, and Treatment and Ongoing Management, led by Amy H. Cheung, MD, of the University of Toronto. They were published online in Pediatrics.
“It has been over 10 years since the [last] guidelines were published and they are supposed to be updated every 5,” Dr. Zuckerbrot said in an interview. “Given the new evidence on screening, psychopharmacology, and collaborative care, the guidelines needed to be revised. The USPSTF [United States Preventive Services Task Force ] and the AAP had already supported universal adolescent depression screening, and these guidelines are finally aligned with those positions.
“Different parts of the guidelines will be the go-to for different pediatricians, depending on where they are in their delivery of mental health care,” she explained. “Some may need help with practice preparation while others may need advice on screening; others may already be prescribing and may need advice on ongoing treatment and follow-up. I think there is something for everyone.”
Implementation of the guidelines is difficult in a short visit, Dr. Zuckerbrot acknowledged. “In addition, pediatricians may not have been well trained in the management of adolescent depression during their residencies.” However, the guidelines discuss both “real teams to support the pediatricians in their efforts, as well as virtual teams when staffing is limited.
“The guidelines advise that pediatricians learn about child psychiatry primary care consultation programs in their state and make use of those free telephone consultation programs.” The guidelines also discuss strategies for collaborative or integrative care, she said.
Part I
Part I of the guidelines, “Practice Preparation, Identification, Assessment, and Initial Management,” includes several recommendations for each topic.
For practice preparation, the guidelines recommend that clinicians seek training in the assessment, diagnosis, and treatment of depression, and that they establish a network of referrals and mental health resources in their communities. This network may include not only health professionals, but also current patients and families who are managing teen depression. If available, state-wide or regional child and adolescent psychiatry consultation programs can be included.
The identification and surveillance section of the guidelines calls for screening all patients aged 12 years and older for depression each year, using a formal screening tool on paper or online. The screening could occur at an annual wellness visit or any other medical visit, such as a sports physical. A second recommendation calls for identifying patients at increased risk for depression because of factors such as personal history, family history, substance use, other psychiatric disorders, frequent somatic complaints, or trauma, and monitoring these individuals regularly for signs of depression using a formal screening tool.
The assessment and diagnosis section states that assessment should include interviews with the patients alone as well as with their families or caregivers, and should include screening teens for functional impairment.
Primary care physicians should evaluate for depression not only if an adolescent tests positive on a screening tool, but also in children who present with any emotional problem as the chief complaint, and in those in whom depression is highly suspected even if they test negative on a formal screening tool, the guidelines state.
The three recommendations for initial management of depression in the primary care setting are educating patients and families about depression; developing a treatment plan (if the primary care clinician has had appropriate training) and setting specific treatment goals in areas of functioning such as at home, with peers, and at school; and developing a safety plan that includes restricting access to weapons or other means of self-harm, according to the guidelines.
Part II
Part II of the recommendations, “Treatment and Ongoing Management,” discusses options for managing depression in the primary care setting and utilizing outside resources.
The treatment recommendations emphasize the use of integrated models, if possible. “There is a growing recognition that complex chronic conditions, such as depression, are most successfully managed with proactive, multidisciplinary, patient-centered care teams,” Dr. Cheung and her associates said.
The recommendation for cases of mild depression calls for a period of “active support and monitoring” for 6-8 weeks before reassessing if the teen shows no improvement. By contrast, for cases of moderate to severe depression or cases with evidence of substance abuse or other psychoses, the recommendation calls for potential consultation with a mental health specialist and a discussion of the roles primary and specialty care will play in treatment. The guidelines include a flow chart for PC physicians to follow.
The guidelines suggest that PC clinicians recommend “scientifically tested and proven treatments,” such as psychotherapies, cognitive behavioral therapy (CBT) or interpersonal psychotherapy for adolescents, and/or antidepressant treatment, such as SSRIs, whenever possible and appropriate. It is important to monitor teens on antidepressants regularly to identify adverse events.
Recommendations for the ongoing management of teens with depression in the primary care setting include regular tracking of progress, reassessment if the teen shows no improvement in 6-8 weeks, and consultation with a mental health professional for those who show only partial improvement after exhausting primary care diagnostic and treatment options. Assessment of depressive symptoms is not the only thing to track. Functioning at home, school, and among peers also is important.
The final treatment recommendation is for active support of a depressed teen’s referral to mental health if necessary for best management and sharing care if possible, with an understanding of the roles of the primary and specialty clinicians, the guidelines state.
The guidelines project was funded by the Resource for Advancing Children’s Health Institute and the Bell Canada Chair in Adolescent Mood and Anxiety Disorders.
Dr. Cheung and Dr. Zuckerbrot receive book royalties. Dr Zuckerbrot works for child and adolescent psychiatry for primary care (CAP-PC), now a regional provider for Project TEACH in New York State, and she is on the steering committee as well as faculty for the REACH Institute; both of these institutions are described in the guidelines. Peter S. Jensen, MD, has received royalties from Random House, Oxford University Press, and APPI Inc. He is a part owner of a consulting company, CATCH Services LLC. He is the chief executive officer and president of a nonprofit organization, the Resource for Advancing Children’s Health Institute, but receives no compensation. The other authors indicated they have no financial relationships relevant to the guidelines.
FROM PEDIATRICS
