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Mammography after breast cancer: No benefit for older patients?
BOSTON – Older women who have had breast cancer frequently undergo annual surveillance mammography, even if there is only a small risk of their developing a second cancer or if they have other mortality risks associated with age and comorbidities.
In a study that included almost 45,000 women who were aged 67 years or older when they were diagnosed with breast cancer, investigators found that patients commonly underwent annual mammographies.
“Even 10 years after their initial diagnosis ... about 40% of them were still getting surveillance mammography well into their 80s and 90s,” noted lead investigator Elizabeth Berger, MD, assistant professor of breast surgical oncology, Yale University, New Haven, Conn.
“Ongoing surveillance mammography in these patients may lead to overdiagnosis and overtreatment of cancers that potentially would not harm patients if left untreated,” Dr. Berger said.
“A positive or false positive finding may unnecessarily erode patient quality of life and incur costs to the patient and health care system without benefit,” she said. She added: “If an elderly woman is in poor health and has significant competing mortality risks compared to breast cancer, annual mammography may not be necessary.”
The research was presented at the annual meeting of the American Society of Breast Surgeons (ASBrS). The study was highlighted in a preview press briefing.
Speaking at the press briefing, Dr. Berger said that the “risks and benefits of surveillance mammography, including its downstream effects, should be considered by both patients and their doctors together to create a shared decision plan.” She acknowledged that the idea of skipping mammograms may be a sensitive one for patients.
She also shared what she described as “exciting news”: “We have just recently received funding from our geriatric group here at Yale to start to evaluate the potential benefits and harms of these surveillance mammographies.”
The aim is to evaluate false positive rates and the potential for overdiagnosis and overtreatment, “so stay tuned,” she added.
Approached for comment, Mediget Teshome, MD, MPH, said it was “not surprising to see the high rates of surveillance mammography, especially in the short term after treatment.”
She said in an interview that the results suggest that it “may be being overused,” given the low rates of second primary breast cancer and the “competing health concerns” of these women.
Overuse can, on the other hand, “definitely be a complex issue,” said Dr. Teshome, associate professor, department of breast surgical oncology, University of Texas MD Anderson Cancer Center, Houston.
“The goal of mammography screening is to identify breast cancer at an early stage,” she explained. She noted that because of the “competing mortality risk from other challenging and life-threatening health problems,” early-stage breast cancer “may not contribute significantly” to the overall mortality risk.
“In general, in this patient population, consideration should be given to stratifying based on an individual patient’s risk of breast cancer recurrence or new breast cancer, estimated life expectancy, as well as shared decision-making with the patient based on their goals of care.”
Study details
To examine the use of surveillance mammography and the risk of subsequent cancers among older women, Dr. Berger and her team used data from the Surveillance, Epidemiology, and End Results (SEER) registry to identify women aged 67 years or older who were diagnosed with a first nonmetastatic beast cancer between 2003 and 2007.
The patients were followed beginning 1 year after diagnosis until the occurrence of a second primary breast cancer, death, or the end of follow-up in 2017.
Data on 44,475 women were analyzed. Of those patients, 30% were older than 80 years. The majority (74%) of breast cancers were of stage I or II, and 72% were hormone receptor–positive (HR+).
Comorbid conditions were common; 55% of women had at least one, and 16% had three or more.
Life expectancy, determined on the basis of age, sex, and comorbidities, was estimated at less than 5 years for 26% of women. For 36% of patients, life expectancy was 6-10 years, and for 38%, it was longer than 10 years.
The cumulative incidence of developing a second primary breast cancer varied by life expectancy and the tumor’s molecular subtype.
The incidence was 3.7% among women with a life expectancy of less than 5 years, 4.9% among those expected to live 6-10 years, and 7.6% among those predicted to live more than 10 years.
Among women with a life expectancy of less than 5 years, the cumulative incidence of a second primary tumor was 4.0% among those with triple-negative breast cancer, vs. 3.0% among those with HR+ breast cancer.
Among patients whose life expectancy was more than 10 years, the cumulative incidence of a second primary tumor was 9.2% among women with triple-negative disease, vs. 7.0% among those with HR+ cancers.
The team found that it was common for women across all the groups to undergo mammography.
Among women with a life expectancy of 6-10 years, 82% underwent at least one mammogram, and 65% underwent five mammograms. Even among women with a life expectancy of less than 1 year, 51% underwent at least one mammogram within 12 months of death.
Among women with a life expectancy of less than 5 years, 68% of women had received a mammogram 1 year after treatment; 53% underwent three mammograms within 3 years after treatment.
No funding for the study was declared. The investigators have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
BOSTON – Older women who have had breast cancer frequently undergo annual surveillance mammography, even if there is only a small risk of their developing a second cancer or if they have other mortality risks associated with age and comorbidities.
In a study that included almost 45,000 women who were aged 67 years or older when they were diagnosed with breast cancer, investigators found that patients commonly underwent annual mammographies.
“Even 10 years after their initial diagnosis ... about 40% of them were still getting surveillance mammography well into their 80s and 90s,” noted lead investigator Elizabeth Berger, MD, assistant professor of breast surgical oncology, Yale University, New Haven, Conn.
“Ongoing surveillance mammography in these patients may lead to overdiagnosis and overtreatment of cancers that potentially would not harm patients if left untreated,” Dr. Berger said.
“A positive or false positive finding may unnecessarily erode patient quality of life and incur costs to the patient and health care system without benefit,” she said. She added: “If an elderly woman is in poor health and has significant competing mortality risks compared to breast cancer, annual mammography may not be necessary.”
The research was presented at the annual meeting of the American Society of Breast Surgeons (ASBrS). The study was highlighted in a preview press briefing.
Speaking at the press briefing, Dr. Berger said that the “risks and benefits of surveillance mammography, including its downstream effects, should be considered by both patients and their doctors together to create a shared decision plan.” She acknowledged that the idea of skipping mammograms may be a sensitive one for patients.
She also shared what she described as “exciting news”: “We have just recently received funding from our geriatric group here at Yale to start to evaluate the potential benefits and harms of these surveillance mammographies.”
The aim is to evaluate false positive rates and the potential for overdiagnosis and overtreatment, “so stay tuned,” she added.
Approached for comment, Mediget Teshome, MD, MPH, said it was “not surprising to see the high rates of surveillance mammography, especially in the short term after treatment.”
She said in an interview that the results suggest that it “may be being overused,” given the low rates of second primary breast cancer and the “competing health concerns” of these women.
Overuse can, on the other hand, “definitely be a complex issue,” said Dr. Teshome, associate professor, department of breast surgical oncology, University of Texas MD Anderson Cancer Center, Houston.
“The goal of mammography screening is to identify breast cancer at an early stage,” she explained. She noted that because of the “competing mortality risk from other challenging and life-threatening health problems,” early-stage breast cancer “may not contribute significantly” to the overall mortality risk.
“In general, in this patient population, consideration should be given to stratifying based on an individual patient’s risk of breast cancer recurrence or new breast cancer, estimated life expectancy, as well as shared decision-making with the patient based on their goals of care.”
Study details
To examine the use of surveillance mammography and the risk of subsequent cancers among older women, Dr. Berger and her team used data from the Surveillance, Epidemiology, and End Results (SEER) registry to identify women aged 67 years or older who were diagnosed with a first nonmetastatic beast cancer between 2003 and 2007.
The patients were followed beginning 1 year after diagnosis until the occurrence of a second primary breast cancer, death, or the end of follow-up in 2017.
Data on 44,475 women were analyzed. Of those patients, 30% were older than 80 years. The majority (74%) of breast cancers were of stage I or II, and 72% were hormone receptor–positive (HR+).
Comorbid conditions were common; 55% of women had at least one, and 16% had three or more.
Life expectancy, determined on the basis of age, sex, and comorbidities, was estimated at less than 5 years for 26% of women. For 36% of patients, life expectancy was 6-10 years, and for 38%, it was longer than 10 years.
The cumulative incidence of developing a second primary breast cancer varied by life expectancy and the tumor’s molecular subtype.
The incidence was 3.7% among women with a life expectancy of less than 5 years, 4.9% among those expected to live 6-10 years, and 7.6% among those predicted to live more than 10 years.
Among women with a life expectancy of less than 5 years, the cumulative incidence of a second primary tumor was 4.0% among those with triple-negative breast cancer, vs. 3.0% among those with HR+ breast cancer.
Among patients whose life expectancy was more than 10 years, the cumulative incidence of a second primary tumor was 9.2% among women with triple-negative disease, vs. 7.0% among those with HR+ cancers.
The team found that it was common for women across all the groups to undergo mammography.
Among women with a life expectancy of 6-10 years, 82% underwent at least one mammogram, and 65% underwent five mammograms. Even among women with a life expectancy of less than 1 year, 51% underwent at least one mammogram within 12 months of death.
Among women with a life expectancy of less than 5 years, 68% of women had received a mammogram 1 year after treatment; 53% underwent three mammograms within 3 years after treatment.
No funding for the study was declared. The investigators have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
BOSTON – Older women who have had breast cancer frequently undergo annual surveillance mammography, even if there is only a small risk of their developing a second cancer or if they have other mortality risks associated with age and comorbidities.
In a study that included almost 45,000 women who were aged 67 years or older when they were diagnosed with breast cancer, investigators found that patients commonly underwent annual mammographies.
“Even 10 years after their initial diagnosis ... about 40% of them were still getting surveillance mammography well into their 80s and 90s,” noted lead investigator Elizabeth Berger, MD, assistant professor of breast surgical oncology, Yale University, New Haven, Conn.
“Ongoing surveillance mammography in these patients may lead to overdiagnosis and overtreatment of cancers that potentially would not harm patients if left untreated,” Dr. Berger said.
“A positive or false positive finding may unnecessarily erode patient quality of life and incur costs to the patient and health care system without benefit,” she said. She added: “If an elderly woman is in poor health and has significant competing mortality risks compared to breast cancer, annual mammography may not be necessary.”
The research was presented at the annual meeting of the American Society of Breast Surgeons (ASBrS). The study was highlighted in a preview press briefing.
Speaking at the press briefing, Dr. Berger said that the “risks and benefits of surveillance mammography, including its downstream effects, should be considered by both patients and their doctors together to create a shared decision plan.” She acknowledged that the idea of skipping mammograms may be a sensitive one for patients.
She also shared what she described as “exciting news”: “We have just recently received funding from our geriatric group here at Yale to start to evaluate the potential benefits and harms of these surveillance mammographies.”
The aim is to evaluate false positive rates and the potential for overdiagnosis and overtreatment, “so stay tuned,” she added.
Approached for comment, Mediget Teshome, MD, MPH, said it was “not surprising to see the high rates of surveillance mammography, especially in the short term after treatment.”
She said in an interview that the results suggest that it “may be being overused,” given the low rates of second primary breast cancer and the “competing health concerns” of these women.
Overuse can, on the other hand, “definitely be a complex issue,” said Dr. Teshome, associate professor, department of breast surgical oncology, University of Texas MD Anderson Cancer Center, Houston.
“The goal of mammography screening is to identify breast cancer at an early stage,” she explained. She noted that because of the “competing mortality risk from other challenging and life-threatening health problems,” early-stage breast cancer “may not contribute significantly” to the overall mortality risk.
“In general, in this patient population, consideration should be given to stratifying based on an individual patient’s risk of breast cancer recurrence or new breast cancer, estimated life expectancy, as well as shared decision-making with the patient based on their goals of care.”
Study details
To examine the use of surveillance mammography and the risk of subsequent cancers among older women, Dr. Berger and her team used data from the Surveillance, Epidemiology, and End Results (SEER) registry to identify women aged 67 years or older who were diagnosed with a first nonmetastatic beast cancer between 2003 and 2007.
The patients were followed beginning 1 year after diagnosis until the occurrence of a second primary breast cancer, death, or the end of follow-up in 2017.
Data on 44,475 women were analyzed. Of those patients, 30% were older than 80 years. The majority (74%) of breast cancers were of stage I or II, and 72% were hormone receptor–positive (HR+).
Comorbid conditions were common; 55% of women had at least one, and 16% had three or more.
Life expectancy, determined on the basis of age, sex, and comorbidities, was estimated at less than 5 years for 26% of women. For 36% of patients, life expectancy was 6-10 years, and for 38%, it was longer than 10 years.
The cumulative incidence of developing a second primary breast cancer varied by life expectancy and the tumor’s molecular subtype.
The incidence was 3.7% among women with a life expectancy of less than 5 years, 4.9% among those expected to live 6-10 years, and 7.6% among those predicted to live more than 10 years.
Among women with a life expectancy of less than 5 years, the cumulative incidence of a second primary tumor was 4.0% among those with triple-negative breast cancer, vs. 3.0% among those with HR+ breast cancer.
Among patients whose life expectancy was more than 10 years, the cumulative incidence of a second primary tumor was 9.2% among women with triple-negative disease, vs. 7.0% among those with HR+ cancers.
The team found that it was common for women across all the groups to undergo mammography.
Among women with a life expectancy of 6-10 years, 82% underwent at least one mammogram, and 65% underwent five mammograms. Even among women with a life expectancy of less than 1 year, 51% underwent at least one mammogram within 12 months of death.
Among women with a life expectancy of less than 5 years, 68% of women had received a mammogram 1 year after treatment; 53% underwent three mammograms within 3 years after treatment.
No funding for the study was declared. The investigators have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ASBRS 2023
Care for patients with gout needs improvement, says doctor
said a presenter at the annual meeting of the American College of Physicians. Failure to understand the disease process and goals of urate-lowering therapy (ULT) is a key barrier to achieving optimal gout therapy.
“There’s too much focus on the flare and too little focus on the urate burden of the disease. Regardless of the clinical setting, the goal should be to manage [high] serum uric acid levels,” said Lawrence Edwards, MD, professor at the University of Florida, Gainesville, during his talk.
Dr. Edwards, who specializes in treating patients with gout and rheumatoid arthritis, discussed the role of primary care providers in the treatment of gout. “We can and must do better,” he said.
Understanding the pathology of gout is key to effective treatment
Knowledge of the molecular pathology of gout has advanced drastically over the last few years. “The improved understanding of the molecules involved in disease initiation and progression can help us make better treatment decisions depending on the stage of the disease,” Dr. Edwards said.
Gout is caused by the deposition of monosodium urate (MSU) crystals, which starts as asymptomatic hyperuricemia, he said. Inflammatory responses to MSU crystals are responsible for gout flares, the frequency of which increases as the disease progresses.
Innate immune responses driven by macrophages and neutrophils play a crucial role in acute gout attacks. In the molecular pathway, proinflammatory cytokines IL-1 beta and IL-6 are the mediators of gout flares, whereas IL-8 accumulates over time and contributes to disease progression and systemic illness. If left untreated or undertreated, the repeated inflammatory reaction leads to advanced gout. The urate burden also increases with disease progression.
“Physicians need to better educate themselves on the destructive nature of this inflammatory arthritis and the need for effective urate-lowering therapy in the management of gout,” Dr. Edwards said.
Management of acute gout attacks
The management of gout flares involves the use of pharmacological agents to control pain and inflammation. The three most common anti-inflammatory therapies are colchicine, NSAIDs, and corticosteroids (either oral or intramuscular).
The choice of which of these should be used alone or in combination for a flare is based on previous tolerance of the medication or the presence of diabetes, kidney disease, heart disease, or a history of upper gastrointestinal bleeding. Dr. Edwards referred internists to the 2020 American College of Rheumatology gout management guideline.
“Regardless of which therapy is chosen, the more important consideration is how quickly the patients can start treatment after the flare begins,” said Dr. Edwards when asked about priorities in the management of gout flares. “This means that the patient should have ready access to whichever the chosen approach is. We call this the ‘pill-in-the-pocket’ approach,” he added.
Reducing the urate burden is also important for effective treatment. The serum urate level is the primary marker of how well a patient’s gout is being managed. ULT should be initiated in patients with subcutaneous tophi, gout-related radiographic damage, or frequent flares (≥ 2 per year). Allopurinol is typically the first-line ULT of choice.
Dr. Edwards noted that far too much focus is placed on flare treatment rather than addressing the underlying sources of gouty symptoms – the elevated serum levels of urate.
Management of advanced gout
“The management of advanced gout is challenging, and the dissolution of MSU is slow unless you take an aggressive approach,” Dr. Edwards said.
Switching to pegloticase is recommended for patients with frequent flares, nonresolving tophi, or high serum urate levels that persist despite treatment with xanthine oxidase inhibitors or other ULT agents.
“The frequency and severity of gout flares are what patients focus on, but if that’s the only focus of the treating physicians, then they are leaving the job less than halfway done. Getting the serum urate to below a level of 6.0 mg/dL is the most important aspect in the lifelong management of gout,” said Dr. Edwards.
Barriers to effective gout treatment
When asked during an interview after the session about the most important barriers to successful gout management, Allison M. Mays, MD, a geriatric medicine subspecialist at Cedars-Sinai Medical Center, Los Angeles, said that “the fact that gout mostly impacts quality of life and not necessarily mortality means that other things may take precedent.” She explained that gout typically coexists with other comorbidities, often multiple ones. Patients may also defer taking an additional medication for a disease like gout, which has only episodic discomfort.
She added that gout management involves shared decision-making between patients and the medical team – including the primary care physician, rheumatologist, orthopedist, and emergency physician. Following a visit to the urgent care or the ED for an acute flare of gout, the patient may not follow up with their primary care doctor or bring it up at their next visit for chronic management, she noted.
Dr. Edwards serves as a consultant to Horizon Pharmaceuticals, Atom Biosciences, Shanton Biosciences, and Aclaris Therapeutics. Horizon marketed pegloticase up until last month when Amgen bought the drug. Dr. Edwards is also president of Gout Education Society, and he has no financial agreement with any of the multiple companies that produce colchicine and allopurinol. Dr. Mays reported no conflicts.
said a presenter at the annual meeting of the American College of Physicians. Failure to understand the disease process and goals of urate-lowering therapy (ULT) is a key barrier to achieving optimal gout therapy.
“There’s too much focus on the flare and too little focus on the urate burden of the disease. Regardless of the clinical setting, the goal should be to manage [high] serum uric acid levels,” said Lawrence Edwards, MD, professor at the University of Florida, Gainesville, during his talk.
Dr. Edwards, who specializes in treating patients with gout and rheumatoid arthritis, discussed the role of primary care providers in the treatment of gout. “We can and must do better,” he said.
Understanding the pathology of gout is key to effective treatment
Knowledge of the molecular pathology of gout has advanced drastically over the last few years. “The improved understanding of the molecules involved in disease initiation and progression can help us make better treatment decisions depending on the stage of the disease,” Dr. Edwards said.
Gout is caused by the deposition of monosodium urate (MSU) crystals, which starts as asymptomatic hyperuricemia, he said. Inflammatory responses to MSU crystals are responsible for gout flares, the frequency of which increases as the disease progresses.
Innate immune responses driven by macrophages and neutrophils play a crucial role in acute gout attacks. In the molecular pathway, proinflammatory cytokines IL-1 beta and IL-6 are the mediators of gout flares, whereas IL-8 accumulates over time and contributes to disease progression and systemic illness. If left untreated or undertreated, the repeated inflammatory reaction leads to advanced gout. The urate burden also increases with disease progression.
“Physicians need to better educate themselves on the destructive nature of this inflammatory arthritis and the need for effective urate-lowering therapy in the management of gout,” Dr. Edwards said.
Management of acute gout attacks
The management of gout flares involves the use of pharmacological agents to control pain and inflammation. The three most common anti-inflammatory therapies are colchicine, NSAIDs, and corticosteroids (either oral or intramuscular).
The choice of which of these should be used alone or in combination for a flare is based on previous tolerance of the medication or the presence of diabetes, kidney disease, heart disease, or a history of upper gastrointestinal bleeding. Dr. Edwards referred internists to the 2020 American College of Rheumatology gout management guideline.
“Regardless of which therapy is chosen, the more important consideration is how quickly the patients can start treatment after the flare begins,” said Dr. Edwards when asked about priorities in the management of gout flares. “This means that the patient should have ready access to whichever the chosen approach is. We call this the ‘pill-in-the-pocket’ approach,” he added.
Reducing the urate burden is also important for effective treatment. The serum urate level is the primary marker of how well a patient’s gout is being managed. ULT should be initiated in patients with subcutaneous tophi, gout-related radiographic damage, or frequent flares (≥ 2 per year). Allopurinol is typically the first-line ULT of choice.
Dr. Edwards noted that far too much focus is placed on flare treatment rather than addressing the underlying sources of gouty symptoms – the elevated serum levels of urate.
Management of advanced gout
“The management of advanced gout is challenging, and the dissolution of MSU is slow unless you take an aggressive approach,” Dr. Edwards said.
Switching to pegloticase is recommended for patients with frequent flares, nonresolving tophi, or high serum urate levels that persist despite treatment with xanthine oxidase inhibitors or other ULT agents.
“The frequency and severity of gout flares are what patients focus on, but if that’s the only focus of the treating physicians, then they are leaving the job less than halfway done. Getting the serum urate to below a level of 6.0 mg/dL is the most important aspect in the lifelong management of gout,” said Dr. Edwards.
Barriers to effective gout treatment
When asked during an interview after the session about the most important barriers to successful gout management, Allison M. Mays, MD, a geriatric medicine subspecialist at Cedars-Sinai Medical Center, Los Angeles, said that “the fact that gout mostly impacts quality of life and not necessarily mortality means that other things may take precedent.” She explained that gout typically coexists with other comorbidities, often multiple ones. Patients may also defer taking an additional medication for a disease like gout, which has only episodic discomfort.
She added that gout management involves shared decision-making between patients and the medical team – including the primary care physician, rheumatologist, orthopedist, and emergency physician. Following a visit to the urgent care or the ED for an acute flare of gout, the patient may not follow up with their primary care doctor or bring it up at their next visit for chronic management, she noted.
Dr. Edwards serves as a consultant to Horizon Pharmaceuticals, Atom Biosciences, Shanton Biosciences, and Aclaris Therapeutics. Horizon marketed pegloticase up until last month when Amgen bought the drug. Dr. Edwards is also president of Gout Education Society, and he has no financial agreement with any of the multiple companies that produce colchicine and allopurinol. Dr. Mays reported no conflicts.
said a presenter at the annual meeting of the American College of Physicians. Failure to understand the disease process and goals of urate-lowering therapy (ULT) is a key barrier to achieving optimal gout therapy.
“There’s too much focus on the flare and too little focus on the urate burden of the disease. Regardless of the clinical setting, the goal should be to manage [high] serum uric acid levels,” said Lawrence Edwards, MD, professor at the University of Florida, Gainesville, during his talk.
Dr. Edwards, who specializes in treating patients with gout and rheumatoid arthritis, discussed the role of primary care providers in the treatment of gout. “We can and must do better,” he said.
Understanding the pathology of gout is key to effective treatment
Knowledge of the molecular pathology of gout has advanced drastically over the last few years. “The improved understanding of the molecules involved in disease initiation and progression can help us make better treatment decisions depending on the stage of the disease,” Dr. Edwards said.
Gout is caused by the deposition of monosodium urate (MSU) crystals, which starts as asymptomatic hyperuricemia, he said. Inflammatory responses to MSU crystals are responsible for gout flares, the frequency of which increases as the disease progresses.
Innate immune responses driven by macrophages and neutrophils play a crucial role in acute gout attacks. In the molecular pathway, proinflammatory cytokines IL-1 beta and IL-6 are the mediators of gout flares, whereas IL-8 accumulates over time and contributes to disease progression and systemic illness. If left untreated or undertreated, the repeated inflammatory reaction leads to advanced gout. The urate burden also increases with disease progression.
“Physicians need to better educate themselves on the destructive nature of this inflammatory arthritis and the need for effective urate-lowering therapy in the management of gout,” Dr. Edwards said.
Management of acute gout attacks
The management of gout flares involves the use of pharmacological agents to control pain and inflammation. The three most common anti-inflammatory therapies are colchicine, NSAIDs, and corticosteroids (either oral or intramuscular).
The choice of which of these should be used alone or in combination for a flare is based on previous tolerance of the medication or the presence of diabetes, kidney disease, heart disease, or a history of upper gastrointestinal bleeding. Dr. Edwards referred internists to the 2020 American College of Rheumatology gout management guideline.
“Regardless of which therapy is chosen, the more important consideration is how quickly the patients can start treatment after the flare begins,” said Dr. Edwards when asked about priorities in the management of gout flares. “This means that the patient should have ready access to whichever the chosen approach is. We call this the ‘pill-in-the-pocket’ approach,” he added.
Reducing the urate burden is also important for effective treatment. The serum urate level is the primary marker of how well a patient’s gout is being managed. ULT should be initiated in patients with subcutaneous tophi, gout-related radiographic damage, or frequent flares (≥ 2 per year). Allopurinol is typically the first-line ULT of choice.
Dr. Edwards noted that far too much focus is placed on flare treatment rather than addressing the underlying sources of gouty symptoms – the elevated serum levels of urate.
Management of advanced gout
“The management of advanced gout is challenging, and the dissolution of MSU is slow unless you take an aggressive approach,” Dr. Edwards said.
Switching to pegloticase is recommended for patients with frequent flares, nonresolving tophi, or high serum urate levels that persist despite treatment with xanthine oxidase inhibitors or other ULT agents.
“The frequency and severity of gout flares are what patients focus on, but if that’s the only focus of the treating physicians, then they are leaving the job less than halfway done. Getting the serum urate to below a level of 6.0 mg/dL is the most important aspect in the lifelong management of gout,” said Dr. Edwards.
Barriers to effective gout treatment
When asked during an interview after the session about the most important barriers to successful gout management, Allison M. Mays, MD, a geriatric medicine subspecialist at Cedars-Sinai Medical Center, Los Angeles, said that “the fact that gout mostly impacts quality of life and not necessarily mortality means that other things may take precedent.” She explained that gout typically coexists with other comorbidities, often multiple ones. Patients may also defer taking an additional medication for a disease like gout, which has only episodic discomfort.
She added that gout management involves shared decision-making between patients and the medical team – including the primary care physician, rheumatologist, orthopedist, and emergency physician. Following a visit to the urgent care or the ED for an acute flare of gout, the patient may not follow up with their primary care doctor or bring it up at their next visit for chronic management, she noted.
Dr. Edwards serves as a consultant to Horizon Pharmaceuticals, Atom Biosciences, Shanton Biosciences, and Aclaris Therapeutics. Horizon marketed pegloticase up until last month when Amgen bought the drug. Dr. Edwards is also president of Gout Education Society, and he has no financial agreement with any of the multiple companies that produce colchicine and allopurinol. Dr. Mays reported no conflicts.
AT INTERNAL MEDICINE 2023
Contact allergens lurk in diabetes devices
in a presentation at the annual meeting of the American Contact Dermatitis Society.
Advanced technologies used for the management of diabetes fall into three main categories, said Dr. Chen, of the department of dermatology, Stanford University, Redwood City, Calif. Continuous glucose monitoring (CGM) devices, which are worn on the body, collect glucose measurements. Continuous subcutaneous insulin infusion (CSII) devices are attached to the body via an infusion set and are now available as tubing-free patch pumps that are attached directly to the skin via a catheter. Glucose-responsive insulin delivery systems combine the sensing and delivery features of the other two types of devices.
Once thought to be rare, reports of skin complications related to diabetes devices have been increasing in recent years, she said. Some reports suggest that at any given time, skin complications may affect as many as one quarter to one half of patients who use these devices, “so this is an important issue,” she emphasized. “Skin reactions are a major factor in device discontinuation, so we as clinicians need to be really proactive about treating these reactions.”
Risk factors for skin complications related to diabetes devices include sensitization to the adhesive used with the devices, as well as prolonged exposure to the device, Dr. Chen said. Younger age also appears to be a risk factor, as is a compromised skin barrier in the area where the device is used.
Unfortunately, obtaining details on the specific adhesives and the raw materials used in these devices, so as to customize patch testing, remains a challenge, she said. “Patch testing initially was often negative to commercially available allergens, even while patients were testing positive to pieces of device adhesive,” she noted.
Consider isobornyl acrylate
An article published in 2017 in Contact Dermatitis was “a major breakthrough” in that it identified isobornyl acrylate (IBOA) as an allergen in connection with the Freestyle Libre, a CGM device that was relatively new at the time. The finding was serendipitous, Dr. Chen said. A patient being treated for suspected allergic contact dermatitis in connection with use of a Freestyle Libre device was tested for IBOA accidentally, after the nurse administering the patch test thought that this was part of the standard acrylate series, she explained.
Subsequently, researchers identified 15 patients who had experienced reactions to the Freestyle Libre; 12 of 13 patients who were patch tested for IBOA tested positive. IBOA was found throughout the device, particularly where the top and bottom plastic components were connected, Dr. Chen said. This suggested that the IBOA was in the device housing and had diffused into the adhesive that attached the device to the skin.
An article published in 2018 in the Journal of Diabetes Science described three patients who developed severe allergic contact dermatitis from IBOA while using a CGM device, Dr. Chen said. The investigators confirmed that there were no reactions to the adhesive itself, again suggesting that IBOA had diffused into the adhesive from other parts of the device.
Although the authors were bound by a confidentiality agreement regarding the individual adhesive components, “the authors noted most of the acrylates in the adhesive were not present in commercially available acrylate series for patch testing,” she said.
IBOA, the ACDS’ Allergen of the Year in 2020, is common in sealants, glues, and adhesives, Dr. Chen said. Although IBOA had been reported infrequently as an allergen, it has now been identified as a “potential culprit” behind skin reactions in many diabetes devices, including CSII and CGM devices, she added.
In addition, N,N-dimethylacrylamide (DMAA) is an allergen that has been identified in several diabetes devices and often occurs with IBOA in medical-grade UV-cured adhesives, Dr. Chen noted. Other allergens identified in diabetes devices include colophony, which is present in many adhesives, as well as other acrylates and epoxy resin.
Diabetes devices are constantly evolving. IBOA is no longer found in Freestyle Libre devices. It is important that clinicians stay up to date with the medical literature and advocate for partnership with device manufacturers, she emphasized.
Patch testing
When diabetes devices are suspected as the source of allergic contact dermatitis, a minimum of a baseline series that contains colophony at a concentration of 20% in petrolatum should be carried out, Dr. Chen said. Commercialized patch test trays, which include plastics, glues, acrylates, epoxy resins/isocyanates, and colophony derivatives, should be ideal. “Personal-care products should be included if they are potentially relevant,” she added.
Dr. Chen shared tables published in Contact Dermatitis in 2021 with examples of screening test series. She said to consider including screening for other allergens more recently discovered in diabetes devices, including 2,2’-methylenebis(6-tert-butyl-4-methylphenol) monoacrylate (MBPA) 1.5% pet; dipropylene glycol diacrylate (DPGDA) 0.1% pet; and butylated hydroxytoluene (BHT) 2% pet.
Testing for monomethyl ether of hydroquinone should also be considered; this may be included in the test preparations for IBOA and DMAA.
Management strategies
For patients who experience skin reactions to their diabetes devices, consideration may given to relocating the device to another area of skin or changing sensors more frequently, according to Dr. Chen.
For some patients, the reaction can be managed with corticosteroid cream, ointment, solution, or nasal spray. Topical antibiotics or topical antihistamines can be helpful, as can barrier dressings, solutions, or sprays, she said. The best solution is to change to a device that does not have the culprit allergen, “but that is difficult, since we don’t know what is in these devices,” she added. Good alternatives include the Eversense CGM device or devices that have been demonstrated not to contain IBOA, such as the Freestyle Libre 2 or the newer version of the Omnipod, an insulin delivery system
Looking ahead, Dr. Chen said that “mandatory labeling is needed, as devices with the same name may have different compositions, depending on the date of manufacture.” Allergens relevant to people with diabetes are constantly evolving, and many are still unidentified, so clinicians and manufacturers need to work together to identify the culprit allergens and their sources, she said.
Dr. Chen has served as principal investigator or subinvestigator for Amgen, AbbVie, and Sanofi Regeneron and as a consultant for Purity Brands.
A version of this article first appeared on Medscape.com.
in a presentation at the annual meeting of the American Contact Dermatitis Society.
Advanced technologies used for the management of diabetes fall into three main categories, said Dr. Chen, of the department of dermatology, Stanford University, Redwood City, Calif. Continuous glucose monitoring (CGM) devices, which are worn on the body, collect glucose measurements. Continuous subcutaneous insulin infusion (CSII) devices are attached to the body via an infusion set and are now available as tubing-free patch pumps that are attached directly to the skin via a catheter. Glucose-responsive insulin delivery systems combine the sensing and delivery features of the other two types of devices.
Once thought to be rare, reports of skin complications related to diabetes devices have been increasing in recent years, she said. Some reports suggest that at any given time, skin complications may affect as many as one quarter to one half of patients who use these devices, “so this is an important issue,” she emphasized. “Skin reactions are a major factor in device discontinuation, so we as clinicians need to be really proactive about treating these reactions.”
Risk factors for skin complications related to diabetes devices include sensitization to the adhesive used with the devices, as well as prolonged exposure to the device, Dr. Chen said. Younger age also appears to be a risk factor, as is a compromised skin barrier in the area where the device is used.
Unfortunately, obtaining details on the specific adhesives and the raw materials used in these devices, so as to customize patch testing, remains a challenge, she said. “Patch testing initially was often negative to commercially available allergens, even while patients were testing positive to pieces of device adhesive,” she noted.
Consider isobornyl acrylate
An article published in 2017 in Contact Dermatitis was “a major breakthrough” in that it identified isobornyl acrylate (IBOA) as an allergen in connection with the Freestyle Libre, a CGM device that was relatively new at the time. The finding was serendipitous, Dr. Chen said. A patient being treated for suspected allergic contact dermatitis in connection with use of a Freestyle Libre device was tested for IBOA accidentally, after the nurse administering the patch test thought that this was part of the standard acrylate series, she explained.
Subsequently, researchers identified 15 patients who had experienced reactions to the Freestyle Libre; 12 of 13 patients who were patch tested for IBOA tested positive. IBOA was found throughout the device, particularly where the top and bottom plastic components were connected, Dr. Chen said. This suggested that the IBOA was in the device housing and had diffused into the adhesive that attached the device to the skin.
An article published in 2018 in the Journal of Diabetes Science described three patients who developed severe allergic contact dermatitis from IBOA while using a CGM device, Dr. Chen said. The investigators confirmed that there were no reactions to the adhesive itself, again suggesting that IBOA had diffused into the adhesive from other parts of the device.
Although the authors were bound by a confidentiality agreement regarding the individual adhesive components, “the authors noted most of the acrylates in the adhesive were not present in commercially available acrylate series for patch testing,” she said.
IBOA, the ACDS’ Allergen of the Year in 2020, is common in sealants, glues, and adhesives, Dr. Chen said. Although IBOA had been reported infrequently as an allergen, it has now been identified as a “potential culprit” behind skin reactions in many diabetes devices, including CSII and CGM devices, she added.
In addition, N,N-dimethylacrylamide (DMAA) is an allergen that has been identified in several diabetes devices and often occurs with IBOA in medical-grade UV-cured adhesives, Dr. Chen noted. Other allergens identified in diabetes devices include colophony, which is present in many adhesives, as well as other acrylates and epoxy resin.
Diabetes devices are constantly evolving. IBOA is no longer found in Freestyle Libre devices. It is important that clinicians stay up to date with the medical literature and advocate for partnership with device manufacturers, she emphasized.
Patch testing
When diabetes devices are suspected as the source of allergic contact dermatitis, a minimum of a baseline series that contains colophony at a concentration of 20% in petrolatum should be carried out, Dr. Chen said. Commercialized patch test trays, which include plastics, glues, acrylates, epoxy resins/isocyanates, and colophony derivatives, should be ideal. “Personal-care products should be included if they are potentially relevant,” she added.
Dr. Chen shared tables published in Contact Dermatitis in 2021 with examples of screening test series. She said to consider including screening for other allergens more recently discovered in diabetes devices, including 2,2’-methylenebis(6-tert-butyl-4-methylphenol) monoacrylate (MBPA) 1.5% pet; dipropylene glycol diacrylate (DPGDA) 0.1% pet; and butylated hydroxytoluene (BHT) 2% pet.
Testing for monomethyl ether of hydroquinone should also be considered; this may be included in the test preparations for IBOA and DMAA.
Management strategies
For patients who experience skin reactions to their diabetes devices, consideration may given to relocating the device to another area of skin or changing sensors more frequently, according to Dr. Chen.
For some patients, the reaction can be managed with corticosteroid cream, ointment, solution, or nasal spray. Topical antibiotics or topical antihistamines can be helpful, as can barrier dressings, solutions, or sprays, she said. The best solution is to change to a device that does not have the culprit allergen, “but that is difficult, since we don’t know what is in these devices,” she added. Good alternatives include the Eversense CGM device or devices that have been demonstrated not to contain IBOA, such as the Freestyle Libre 2 or the newer version of the Omnipod, an insulin delivery system
Looking ahead, Dr. Chen said that “mandatory labeling is needed, as devices with the same name may have different compositions, depending on the date of manufacture.” Allergens relevant to people with diabetes are constantly evolving, and many are still unidentified, so clinicians and manufacturers need to work together to identify the culprit allergens and their sources, she said.
Dr. Chen has served as principal investigator or subinvestigator for Amgen, AbbVie, and Sanofi Regeneron and as a consultant for Purity Brands.
A version of this article first appeared on Medscape.com.
in a presentation at the annual meeting of the American Contact Dermatitis Society.
Advanced technologies used for the management of diabetes fall into three main categories, said Dr. Chen, of the department of dermatology, Stanford University, Redwood City, Calif. Continuous glucose monitoring (CGM) devices, which are worn on the body, collect glucose measurements. Continuous subcutaneous insulin infusion (CSII) devices are attached to the body via an infusion set and are now available as tubing-free patch pumps that are attached directly to the skin via a catheter. Glucose-responsive insulin delivery systems combine the sensing and delivery features of the other two types of devices.
Once thought to be rare, reports of skin complications related to diabetes devices have been increasing in recent years, she said. Some reports suggest that at any given time, skin complications may affect as many as one quarter to one half of patients who use these devices, “so this is an important issue,” she emphasized. “Skin reactions are a major factor in device discontinuation, so we as clinicians need to be really proactive about treating these reactions.”
Risk factors for skin complications related to diabetes devices include sensitization to the adhesive used with the devices, as well as prolonged exposure to the device, Dr. Chen said. Younger age also appears to be a risk factor, as is a compromised skin barrier in the area where the device is used.
Unfortunately, obtaining details on the specific adhesives and the raw materials used in these devices, so as to customize patch testing, remains a challenge, she said. “Patch testing initially was often negative to commercially available allergens, even while patients were testing positive to pieces of device adhesive,” she noted.
Consider isobornyl acrylate
An article published in 2017 in Contact Dermatitis was “a major breakthrough” in that it identified isobornyl acrylate (IBOA) as an allergen in connection with the Freestyle Libre, a CGM device that was relatively new at the time. The finding was serendipitous, Dr. Chen said. A patient being treated for suspected allergic contact dermatitis in connection with use of a Freestyle Libre device was tested for IBOA accidentally, after the nurse administering the patch test thought that this was part of the standard acrylate series, she explained.
Subsequently, researchers identified 15 patients who had experienced reactions to the Freestyle Libre; 12 of 13 patients who were patch tested for IBOA tested positive. IBOA was found throughout the device, particularly where the top and bottom plastic components were connected, Dr. Chen said. This suggested that the IBOA was in the device housing and had diffused into the adhesive that attached the device to the skin.
An article published in 2018 in the Journal of Diabetes Science described three patients who developed severe allergic contact dermatitis from IBOA while using a CGM device, Dr. Chen said. The investigators confirmed that there were no reactions to the adhesive itself, again suggesting that IBOA had diffused into the adhesive from other parts of the device.
Although the authors were bound by a confidentiality agreement regarding the individual adhesive components, “the authors noted most of the acrylates in the adhesive were not present in commercially available acrylate series for patch testing,” she said.
IBOA, the ACDS’ Allergen of the Year in 2020, is common in sealants, glues, and adhesives, Dr. Chen said. Although IBOA had been reported infrequently as an allergen, it has now been identified as a “potential culprit” behind skin reactions in many diabetes devices, including CSII and CGM devices, she added.
In addition, N,N-dimethylacrylamide (DMAA) is an allergen that has been identified in several diabetes devices and often occurs with IBOA in medical-grade UV-cured adhesives, Dr. Chen noted. Other allergens identified in diabetes devices include colophony, which is present in many adhesives, as well as other acrylates and epoxy resin.
Diabetes devices are constantly evolving. IBOA is no longer found in Freestyle Libre devices. It is important that clinicians stay up to date with the medical literature and advocate for partnership with device manufacturers, she emphasized.
Patch testing
When diabetes devices are suspected as the source of allergic contact dermatitis, a minimum of a baseline series that contains colophony at a concentration of 20% in petrolatum should be carried out, Dr. Chen said. Commercialized patch test trays, which include plastics, glues, acrylates, epoxy resins/isocyanates, and colophony derivatives, should be ideal. “Personal-care products should be included if they are potentially relevant,” she added.
Dr. Chen shared tables published in Contact Dermatitis in 2021 with examples of screening test series. She said to consider including screening for other allergens more recently discovered in diabetes devices, including 2,2’-methylenebis(6-tert-butyl-4-methylphenol) monoacrylate (MBPA) 1.5% pet; dipropylene glycol diacrylate (DPGDA) 0.1% pet; and butylated hydroxytoluene (BHT) 2% pet.
Testing for monomethyl ether of hydroquinone should also be considered; this may be included in the test preparations for IBOA and DMAA.
Management strategies
For patients who experience skin reactions to their diabetes devices, consideration may given to relocating the device to another area of skin or changing sensors more frequently, according to Dr. Chen.
For some patients, the reaction can be managed with corticosteroid cream, ointment, solution, or nasal spray. Topical antibiotics or topical antihistamines can be helpful, as can barrier dressings, solutions, or sprays, she said. The best solution is to change to a device that does not have the culprit allergen, “but that is difficult, since we don’t know what is in these devices,” she added. Good alternatives include the Eversense CGM device or devices that have been demonstrated not to contain IBOA, such as the Freestyle Libre 2 or the newer version of the Omnipod, an insulin delivery system
Looking ahead, Dr. Chen said that “mandatory labeling is needed, as devices with the same name may have different compositions, depending on the date of manufacture.” Allergens relevant to people with diabetes are constantly evolving, and many are still unidentified, so clinicians and manufacturers need to work together to identify the culprit allergens and their sources, she said.
Dr. Chen has served as principal investigator or subinvestigator for Amgen, AbbVie, and Sanofi Regeneron and as a consultant for Purity Brands.
A version of this article first appeared on Medscape.com.
FROM ACDS 2023
Beware the hidden allergens in nutritional supplements
, Alison Ehrlich, MD, said at the annual meeting of the American Contact Dermatitis Society.
Allergens may be hidden in a range of supplement products, from colorings in vitamin C powders to some vitamins used in hair products and other products.
“In general, our patients do not tell us what supplements they are taking,” said Dr. Ehrlich, a dermatologist who practices in Washington, D.C. Antiaging, sleep, and weight loss/weight control supplements are among the most popular, she said.
Surveys have shown that many patients do not discuss supplement use with their health care providers, in part because they believe their providers would disapprove of supplement use, and patients are not educated about supplements, she said. “This is definitely an area that we should try to learn more about,” she added.
Current regulations regarding dietary supplements stem from the Dietary Supplement Health and Education Act of 1994, which defined dietary supplements as distinct from meals but regulated them as a category of food, not as medications. Dietary supplements can be vitamins, minerals, herbs, and extracts, Dr. Ehrlich said.
“There is not a lot of safety wrapped around how supplements come onto the market,” she explained. “It is not the manufacturer’s responsibility to test these products and make sure they are safe. When they get pulled off the market, it is because safety reports are getting back to the FDA.”
Consequently, a detailed history of supplement use is important, as it may reveal possible allergens as the cause of previously unidentified reactions, she said.
Dr. Ehrlich shared a case involving a patient who claimed to have had a reaction to a “Prevage-like” product that was labeled as a crepe repair cream. Listed among the product’s ingredients was idebenone, a synthetic version of the popular antioxidant known as Coenzyme Q.
Be wary of vitamins
Another potential source of allergy is vitamin C supplements, which became especially popular during the pandemic as people sought additional immune system support, Dr. Ehrlich noted. “What kind of vitamin C product our patients are taking is important,” she said. For example, some vitamin C powders contain coloring agents, such as carmine. Some also contain gelatin, which may cause an allergic reaction in individuals with alpha-gal syndrome, she added.
In general, water-soluble vitamins such as vitamins B1 to B9, B12, and C are more likely to cause an immediate reaction, Dr. Ehrlich said. Fat-soluble vitamins, such as vitamins A, D, E, and K, are more likely to cause a delayed reaction of allergic contact dermatitis.
Dr. Ehrlich described some unusual reactions to vitamins that have been reported, including a systemic allergy associated with vitamin B1 (thiamine), burning mouth syndrome associated with vitamin B3 (nicotinate), contact urticaria associated with vitamin B5 (panthenol), systemic allergy and generalized ACD associated with vitamin E (tocopherol), and erythema multiforme–like ACD associated with vitamin K1.
Notably, vitamin B5 has been associated with ACD as an ingredient in hair products, moisturizers, and wound care products, as well as B-complex vitamins and fortified foods, Dr. Ehrlich said.
Herbs and spices can act as allergens as well. Turmeric is a spice that has become a popular supplement ingredient, she said. Turmeric and curcumin (found in turmeric) can be used as a dye for its yellow color as well as a flavoring but has been associated with allergic reactions. Another popular herbal supplement, ginkgo biloba, has been marketed as a product that improves memory and cognition. It is available in pill form and in herbal teas.
“It’s really important to think about what herbal products our patients are taking, and not just in pill form,” Dr. Ehrlich said. “We need to expand our thoughts on what the herbs are in.”
Consider food additives as allergens
Food additives, in the form of colorants, preservatives, or flavoring agents, can cause allergic reactions, Dr. Ehrlich noted.
The question of whether food-additive contact sensitivity has a role in the occurrence of atopic dermatitis (AD) in children remains unclear, she said. However, a study published in 2020 found that 62% of children with AD had positive patch test reactions to at least one food-additive allergen, compared with 20% of children without AD. The additives responsible for the most reactions were azorubine (24.4%); formic acid (15.6%); and carmine, cochineal red, and amaranth (13.3% for each).
Common colorant culprits in allergic reactions include carmine, annatto, tartrazine, and spices (such as paprika and saffron), Dr. Ehrlich said. Carmine is used in meat to prevent photo-oxidation and to preserve a red color, and it has other uses as well, she said. Carmine has been associated with ACD, AD flares, and immediate hypersensitivity. Annatto is used in foods, including processed foods, butter, and cheese, to provide a yellow color. It is also found in some lipsticks and has been associated with urticaria and angioedema, she noted.
Food preservatives that have been associated with allergic reactions include butylated hydroxyanisole and sulfites, Dr. Ehrlich said. Sulfites are used to prevent food from turning brown, and it may be present in dried fruit, fruit juice, molasses, pickled foods, vinegar, and wine.
Reports of ACD in response to sodium metabisulfite have been increasing, she noted. Other sulfite reactions may occur with exposure to other products, such as cosmetics, body washes, and swimming pool water, she said.
Awareness of allergens in supplements is important “because the number of our patients taking supplements for different reasons is increasing” and allergens in supplements could account for flares, Dr. Ehrlich said. Clinicians should encourage patients to tell them what supplements they use. Clinicians should review the ingredients in these supplements with their patients to identify potential allergens that may be causing reactions, she advised.
Dr. Ehrlich has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, Alison Ehrlich, MD, said at the annual meeting of the American Contact Dermatitis Society.
Allergens may be hidden in a range of supplement products, from colorings in vitamin C powders to some vitamins used in hair products and other products.
“In general, our patients do not tell us what supplements they are taking,” said Dr. Ehrlich, a dermatologist who practices in Washington, D.C. Antiaging, sleep, and weight loss/weight control supplements are among the most popular, she said.
Surveys have shown that many patients do not discuss supplement use with their health care providers, in part because they believe their providers would disapprove of supplement use, and patients are not educated about supplements, she said. “This is definitely an area that we should try to learn more about,” she added.
Current regulations regarding dietary supplements stem from the Dietary Supplement Health and Education Act of 1994, which defined dietary supplements as distinct from meals but regulated them as a category of food, not as medications. Dietary supplements can be vitamins, minerals, herbs, and extracts, Dr. Ehrlich said.
“There is not a lot of safety wrapped around how supplements come onto the market,” she explained. “It is not the manufacturer’s responsibility to test these products and make sure they are safe. When they get pulled off the market, it is because safety reports are getting back to the FDA.”
Consequently, a detailed history of supplement use is important, as it may reveal possible allergens as the cause of previously unidentified reactions, she said.
Dr. Ehrlich shared a case involving a patient who claimed to have had a reaction to a “Prevage-like” product that was labeled as a crepe repair cream. Listed among the product’s ingredients was idebenone, a synthetic version of the popular antioxidant known as Coenzyme Q.
Be wary of vitamins
Another potential source of allergy is vitamin C supplements, which became especially popular during the pandemic as people sought additional immune system support, Dr. Ehrlich noted. “What kind of vitamin C product our patients are taking is important,” she said. For example, some vitamin C powders contain coloring agents, such as carmine. Some also contain gelatin, which may cause an allergic reaction in individuals with alpha-gal syndrome, she added.
In general, water-soluble vitamins such as vitamins B1 to B9, B12, and C are more likely to cause an immediate reaction, Dr. Ehrlich said. Fat-soluble vitamins, such as vitamins A, D, E, and K, are more likely to cause a delayed reaction of allergic contact dermatitis.
Dr. Ehrlich described some unusual reactions to vitamins that have been reported, including a systemic allergy associated with vitamin B1 (thiamine), burning mouth syndrome associated with vitamin B3 (nicotinate), contact urticaria associated with vitamin B5 (panthenol), systemic allergy and generalized ACD associated with vitamin E (tocopherol), and erythema multiforme–like ACD associated with vitamin K1.
Notably, vitamin B5 has been associated with ACD as an ingredient in hair products, moisturizers, and wound care products, as well as B-complex vitamins and fortified foods, Dr. Ehrlich said.
Herbs and spices can act as allergens as well. Turmeric is a spice that has become a popular supplement ingredient, she said. Turmeric and curcumin (found in turmeric) can be used as a dye for its yellow color as well as a flavoring but has been associated with allergic reactions. Another popular herbal supplement, ginkgo biloba, has been marketed as a product that improves memory and cognition. It is available in pill form and in herbal teas.
“It’s really important to think about what herbal products our patients are taking, and not just in pill form,” Dr. Ehrlich said. “We need to expand our thoughts on what the herbs are in.”
Consider food additives as allergens
Food additives, in the form of colorants, preservatives, or flavoring agents, can cause allergic reactions, Dr. Ehrlich noted.
The question of whether food-additive contact sensitivity has a role in the occurrence of atopic dermatitis (AD) in children remains unclear, she said. However, a study published in 2020 found that 62% of children with AD had positive patch test reactions to at least one food-additive allergen, compared with 20% of children without AD. The additives responsible for the most reactions were azorubine (24.4%); formic acid (15.6%); and carmine, cochineal red, and amaranth (13.3% for each).
Common colorant culprits in allergic reactions include carmine, annatto, tartrazine, and spices (such as paprika and saffron), Dr. Ehrlich said. Carmine is used in meat to prevent photo-oxidation and to preserve a red color, and it has other uses as well, she said. Carmine has been associated with ACD, AD flares, and immediate hypersensitivity. Annatto is used in foods, including processed foods, butter, and cheese, to provide a yellow color. It is also found in some lipsticks and has been associated with urticaria and angioedema, she noted.
Food preservatives that have been associated with allergic reactions include butylated hydroxyanisole and sulfites, Dr. Ehrlich said. Sulfites are used to prevent food from turning brown, and it may be present in dried fruit, fruit juice, molasses, pickled foods, vinegar, and wine.
Reports of ACD in response to sodium metabisulfite have been increasing, she noted. Other sulfite reactions may occur with exposure to other products, such as cosmetics, body washes, and swimming pool water, she said.
Awareness of allergens in supplements is important “because the number of our patients taking supplements for different reasons is increasing” and allergens in supplements could account for flares, Dr. Ehrlich said. Clinicians should encourage patients to tell them what supplements they use. Clinicians should review the ingredients in these supplements with their patients to identify potential allergens that may be causing reactions, she advised.
Dr. Ehrlich has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, Alison Ehrlich, MD, said at the annual meeting of the American Contact Dermatitis Society.
Allergens may be hidden in a range of supplement products, from colorings in vitamin C powders to some vitamins used in hair products and other products.
“In general, our patients do not tell us what supplements they are taking,” said Dr. Ehrlich, a dermatologist who practices in Washington, D.C. Antiaging, sleep, and weight loss/weight control supplements are among the most popular, she said.
Surveys have shown that many patients do not discuss supplement use with their health care providers, in part because they believe their providers would disapprove of supplement use, and patients are not educated about supplements, she said. “This is definitely an area that we should try to learn more about,” she added.
Current regulations regarding dietary supplements stem from the Dietary Supplement Health and Education Act of 1994, which defined dietary supplements as distinct from meals but regulated them as a category of food, not as medications. Dietary supplements can be vitamins, minerals, herbs, and extracts, Dr. Ehrlich said.
“There is not a lot of safety wrapped around how supplements come onto the market,” she explained. “It is not the manufacturer’s responsibility to test these products and make sure they are safe. When they get pulled off the market, it is because safety reports are getting back to the FDA.”
Consequently, a detailed history of supplement use is important, as it may reveal possible allergens as the cause of previously unidentified reactions, she said.
Dr. Ehrlich shared a case involving a patient who claimed to have had a reaction to a “Prevage-like” product that was labeled as a crepe repair cream. Listed among the product’s ingredients was idebenone, a synthetic version of the popular antioxidant known as Coenzyme Q.
Be wary of vitamins
Another potential source of allergy is vitamin C supplements, which became especially popular during the pandemic as people sought additional immune system support, Dr. Ehrlich noted. “What kind of vitamin C product our patients are taking is important,” she said. For example, some vitamin C powders contain coloring agents, such as carmine. Some also contain gelatin, which may cause an allergic reaction in individuals with alpha-gal syndrome, she added.
In general, water-soluble vitamins such as vitamins B1 to B9, B12, and C are more likely to cause an immediate reaction, Dr. Ehrlich said. Fat-soluble vitamins, such as vitamins A, D, E, and K, are more likely to cause a delayed reaction of allergic contact dermatitis.
Dr. Ehrlich described some unusual reactions to vitamins that have been reported, including a systemic allergy associated with vitamin B1 (thiamine), burning mouth syndrome associated with vitamin B3 (nicotinate), contact urticaria associated with vitamin B5 (panthenol), systemic allergy and generalized ACD associated with vitamin E (tocopherol), and erythema multiforme–like ACD associated with vitamin K1.
Notably, vitamin B5 has been associated with ACD as an ingredient in hair products, moisturizers, and wound care products, as well as B-complex vitamins and fortified foods, Dr. Ehrlich said.
Herbs and spices can act as allergens as well. Turmeric is a spice that has become a popular supplement ingredient, she said. Turmeric and curcumin (found in turmeric) can be used as a dye for its yellow color as well as a flavoring but has been associated with allergic reactions. Another popular herbal supplement, ginkgo biloba, has been marketed as a product that improves memory and cognition. It is available in pill form and in herbal teas.
“It’s really important to think about what herbal products our patients are taking, and not just in pill form,” Dr. Ehrlich said. “We need to expand our thoughts on what the herbs are in.”
Consider food additives as allergens
Food additives, in the form of colorants, preservatives, or flavoring agents, can cause allergic reactions, Dr. Ehrlich noted.
The question of whether food-additive contact sensitivity has a role in the occurrence of atopic dermatitis (AD) in children remains unclear, she said. However, a study published in 2020 found that 62% of children with AD had positive patch test reactions to at least one food-additive allergen, compared with 20% of children without AD. The additives responsible for the most reactions were azorubine (24.4%); formic acid (15.6%); and carmine, cochineal red, and amaranth (13.3% for each).
Common colorant culprits in allergic reactions include carmine, annatto, tartrazine, and spices (such as paprika and saffron), Dr. Ehrlich said. Carmine is used in meat to prevent photo-oxidation and to preserve a red color, and it has other uses as well, she said. Carmine has been associated with ACD, AD flares, and immediate hypersensitivity. Annatto is used in foods, including processed foods, butter, and cheese, to provide a yellow color. It is also found in some lipsticks and has been associated with urticaria and angioedema, she noted.
Food preservatives that have been associated with allergic reactions include butylated hydroxyanisole and sulfites, Dr. Ehrlich said. Sulfites are used to prevent food from turning brown, and it may be present in dried fruit, fruit juice, molasses, pickled foods, vinegar, and wine.
Reports of ACD in response to sodium metabisulfite have been increasing, she noted. Other sulfite reactions may occur with exposure to other products, such as cosmetics, body washes, and swimming pool water, she said.
Awareness of allergens in supplements is important “because the number of our patients taking supplements for different reasons is increasing” and allergens in supplements could account for flares, Dr. Ehrlich said. Clinicians should encourage patients to tell them what supplements they use. Clinicians should review the ingredients in these supplements with their patients to identify potential allergens that may be causing reactions, she advised.
Dr. Ehrlich has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ACDS 2023
Intraoperative pathology spurs overtreatment in mastectomy
(AxRT), warned U.S. investigators.
The team studied data on more than 40,000 clinically node-negative women who underwent upfront mastectomy. Just over 8,000 patients were found to have one to two SLN, with intraoperative pathology performed in approximately one-third.
Intraoperative pathology was associated with a more than eightfold increase in the likelihood of performing both ALND and AxRT, far more than any other factor.
These results provide “evidence that a significant percentage of the mastectomy patients with limited disease in up to two SLNs may be overtreated. … simply because their pathology results are read and acted on while they are on the operating table,” said senior author Olga Kantor, MD, MS, associate program director, Breast Surgical Oncology Fellowship Program, Brigham and Women’s Hospital and Dana-Farber Cancer Institute, Boston.
“Notably, postsurgical decisions typically involve a multidisciplinary team, including radiation oncologists, which will likely result in a more integrated overall treatment plan,” she commented in a statement.
“This study suggests that surgeons should delay ALND decision-making until a later time to avoid overtreating patients,” Dr. Kantor emphasized.
The research was presented at the annual meeting of the American Society of Breast Surgeons, and was highlighted in a premeeting press briefing.
Approached for comment on the new findings, Sarah L. Blair, MD, professor and vice chair, department of surgery, University of California San Diego Health, noted that “there is a great deal of data on deescalation in axillary surgery in patients undergoing breast conservation with radiation.”
Dr. Blair, who was not involved in the study, noted that, while there are some studies in mastectomy patients with equal oncologic results, “the topic remains more controversial.”
“This study highlights that surgeons strongly consider deescalating axillary surgery in mastectomy patients to reduce long-term complications,” she said in an interview.
“If possible, these patients should be discussed in a multidisciplinary fashion ahead of time,” she emphasized.
“If surgeons send the lymph nodes for frozen section then, as this paper demonstrates, they will act on the information and perform axillary dissection for early-stage disease.”
Study details
At the press briefing for the study, Dr. Kantor explained that several clinical trials, including AMAROS, have already “established the safety of axillary observation or AxRT as an alternative to ALND” in clinically node-negative breast cancer patients found to have one to two positive SLN.
She noted that “mastectomy patients were included in these trials, but they made up a minority” of the populations, ranging from 9% to 18%, “and so controversy remains over the optimal axillary management” in this patient population.
Dr. Kantor said that intraoperative pathology assessment “can help avoid the need to return to the operating room for additional axillary surgery” by checking the SLN at the time.
However, acting on the results during the procedure “does not allow for multidisciplinary discussion” and can mean that patients end up having both ALND and postoperative AxRT.
“This dual approach may result in axillary overtreatment in patients who may otherwise have been eligible for axillary radiation alone,” she underlined.
Moreover, a recent survey of 680 surgeons by the ASBrS found that 52% were performing routine intraoperative pathology assessment of SLN, and 78% of those said they would perform ALND if the results came back positive.
To investigate the impact of intraoperative pathology assessment on axillary management in mastectomy patients who would have been eligible for the AMAROS trial, the team examined data from the U.S. National Cancer Database.
They included cT1-2N0 breast cancer patients who had upfront mastectomy in 2018-2019 and were found to have one to two positive SLN.
They defined intraoperative pathology assessment as:
- “Not done/not acted on” if ALND was either not performed or performed at a later date than the pathology assessment.
- “Done/acted on” if both ALND and the pathology assessment were carried out on the same day.
In addition, AxRT was defined as postmastectomy radiation to the chest wall that included radiation to the draining lymph nodes.
The researchers identified 40,467 patients, of whom 20.3% had one to two positive SLN. Among those, axillary management consisted of observation in 33.2%, ALND in 26.6%, AxRT in 22.2%, and ALND plus AxRT in 18.0%.
Overall, 37.2% of the patients underwent intraoperative pathology and 62.8% did not, 11.8% of whom later returned to the operating room for ALND.
Patients who underwent intraoperative pathology were more likely than those who did not to have cT2 disease (48.0% vs. 44.1%), lympho-vascular invasion (43.4% vs. 37.1%), two positive SLN (26.5% vs. 19.2%), and macrometastasis (87.6% vs. 64.2%, P < .001 for all).
Rates of ALND plus AxRT were significantly higher in patients who had intraoperative pathology done/acted on than in those whom intraoperative pathology was not done/not acted on, at 41.0% vs. 4.9% (P < .001).
Adjusted multivariate analysis indicated that receipt of ALND plus AxRT was significantly associated with intraoperative pathology being done/acted on vs. being not done/acted on, at an odds ratio of 8.99 (P < .001).
There were also significant associations between having both procedures and macrometastasis in the SLN, at an odds ratio vs. micrometastasis of 3.38 (P < .001), and the number of total positive SLN, at odds ratio vs. 1 of 2.14 for two nodes, 3.92 for three nodes, and 5.32 for > three nodes (P < .001 for all).
The researchers also found that lobular tumors on histologic analysis were associated with having ALND plus AxRT, at an odds ratio vs. ductal histology of 1.40 (P < .001).
No funding was declared. Dr. Kantor and Dr. Blair report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
(AxRT), warned U.S. investigators.
The team studied data on more than 40,000 clinically node-negative women who underwent upfront mastectomy. Just over 8,000 patients were found to have one to two SLN, with intraoperative pathology performed in approximately one-third.
Intraoperative pathology was associated with a more than eightfold increase in the likelihood of performing both ALND and AxRT, far more than any other factor.
These results provide “evidence that a significant percentage of the mastectomy patients with limited disease in up to two SLNs may be overtreated. … simply because their pathology results are read and acted on while they are on the operating table,” said senior author Olga Kantor, MD, MS, associate program director, Breast Surgical Oncology Fellowship Program, Brigham and Women’s Hospital and Dana-Farber Cancer Institute, Boston.
“Notably, postsurgical decisions typically involve a multidisciplinary team, including radiation oncologists, which will likely result in a more integrated overall treatment plan,” she commented in a statement.
“This study suggests that surgeons should delay ALND decision-making until a later time to avoid overtreating patients,” Dr. Kantor emphasized.
The research was presented at the annual meeting of the American Society of Breast Surgeons, and was highlighted in a premeeting press briefing.
Approached for comment on the new findings, Sarah L. Blair, MD, professor and vice chair, department of surgery, University of California San Diego Health, noted that “there is a great deal of data on deescalation in axillary surgery in patients undergoing breast conservation with radiation.”
Dr. Blair, who was not involved in the study, noted that, while there are some studies in mastectomy patients with equal oncologic results, “the topic remains more controversial.”
“This study highlights that surgeons strongly consider deescalating axillary surgery in mastectomy patients to reduce long-term complications,” she said in an interview.
“If possible, these patients should be discussed in a multidisciplinary fashion ahead of time,” she emphasized.
“If surgeons send the lymph nodes for frozen section then, as this paper demonstrates, they will act on the information and perform axillary dissection for early-stage disease.”
Study details
At the press briefing for the study, Dr. Kantor explained that several clinical trials, including AMAROS, have already “established the safety of axillary observation or AxRT as an alternative to ALND” in clinically node-negative breast cancer patients found to have one to two positive SLN.
She noted that “mastectomy patients were included in these trials, but they made up a minority” of the populations, ranging from 9% to 18%, “and so controversy remains over the optimal axillary management” in this patient population.
Dr. Kantor said that intraoperative pathology assessment “can help avoid the need to return to the operating room for additional axillary surgery” by checking the SLN at the time.
However, acting on the results during the procedure “does not allow for multidisciplinary discussion” and can mean that patients end up having both ALND and postoperative AxRT.
“This dual approach may result in axillary overtreatment in patients who may otherwise have been eligible for axillary radiation alone,” she underlined.
Moreover, a recent survey of 680 surgeons by the ASBrS found that 52% were performing routine intraoperative pathology assessment of SLN, and 78% of those said they would perform ALND if the results came back positive.
To investigate the impact of intraoperative pathology assessment on axillary management in mastectomy patients who would have been eligible for the AMAROS trial, the team examined data from the U.S. National Cancer Database.
They included cT1-2N0 breast cancer patients who had upfront mastectomy in 2018-2019 and were found to have one to two positive SLN.
They defined intraoperative pathology assessment as:
- “Not done/not acted on” if ALND was either not performed or performed at a later date than the pathology assessment.
- “Done/acted on” if both ALND and the pathology assessment were carried out on the same day.
In addition, AxRT was defined as postmastectomy radiation to the chest wall that included radiation to the draining lymph nodes.
The researchers identified 40,467 patients, of whom 20.3% had one to two positive SLN. Among those, axillary management consisted of observation in 33.2%, ALND in 26.6%, AxRT in 22.2%, and ALND plus AxRT in 18.0%.
Overall, 37.2% of the patients underwent intraoperative pathology and 62.8% did not, 11.8% of whom later returned to the operating room for ALND.
Patients who underwent intraoperative pathology were more likely than those who did not to have cT2 disease (48.0% vs. 44.1%), lympho-vascular invasion (43.4% vs. 37.1%), two positive SLN (26.5% vs. 19.2%), and macrometastasis (87.6% vs. 64.2%, P < .001 for all).
Rates of ALND plus AxRT were significantly higher in patients who had intraoperative pathology done/acted on than in those whom intraoperative pathology was not done/not acted on, at 41.0% vs. 4.9% (P < .001).
Adjusted multivariate analysis indicated that receipt of ALND plus AxRT was significantly associated with intraoperative pathology being done/acted on vs. being not done/acted on, at an odds ratio of 8.99 (P < .001).
There were also significant associations between having both procedures and macrometastasis in the SLN, at an odds ratio vs. micrometastasis of 3.38 (P < .001), and the number of total positive SLN, at odds ratio vs. 1 of 2.14 for two nodes, 3.92 for three nodes, and 5.32 for > three nodes (P < .001 for all).
The researchers also found that lobular tumors on histologic analysis were associated with having ALND plus AxRT, at an odds ratio vs. ductal histology of 1.40 (P < .001).
No funding was declared. Dr. Kantor and Dr. Blair report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
(AxRT), warned U.S. investigators.
The team studied data on more than 40,000 clinically node-negative women who underwent upfront mastectomy. Just over 8,000 patients were found to have one to two SLN, with intraoperative pathology performed in approximately one-third.
Intraoperative pathology was associated with a more than eightfold increase in the likelihood of performing both ALND and AxRT, far more than any other factor.
These results provide “evidence that a significant percentage of the mastectomy patients with limited disease in up to two SLNs may be overtreated. … simply because their pathology results are read and acted on while they are on the operating table,” said senior author Olga Kantor, MD, MS, associate program director, Breast Surgical Oncology Fellowship Program, Brigham and Women’s Hospital and Dana-Farber Cancer Institute, Boston.
“Notably, postsurgical decisions typically involve a multidisciplinary team, including radiation oncologists, which will likely result in a more integrated overall treatment plan,” she commented in a statement.
“This study suggests that surgeons should delay ALND decision-making until a later time to avoid overtreating patients,” Dr. Kantor emphasized.
The research was presented at the annual meeting of the American Society of Breast Surgeons, and was highlighted in a premeeting press briefing.
Approached for comment on the new findings, Sarah L. Blair, MD, professor and vice chair, department of surgery, University of California San Diego Health, noted that “there is a great deal of data on deescalation in axillary surgery in patients undergoing breast conservation with radiation.”
Dr. Blair, who was not involved in the study, noted that, while there are some studies in mastectomy patients with equal oncologic results, “the topic remains more controversial.”
“This study highlights that surgeons strongly consider deescalating axillary surgery in mastectomy patients to reduce long-term complications,” she said in an interview.
“If possible, these patients should be discussed in a multidisciplinary fashion ahead of time,” she emphasized.
“If surgeons send the lymph nodes for frozen section then, as this paper demonstrates, they will act on the information and perform axillary dissection for early-stage disease.”
Study details
At the press briefing for the study, Dr. Kantor explained that several clinical trials, including AMAROS, have already “established the safety of axillary observation or AxRT as an alternative to ALND” in clinically node-negative breast cancer patients found to have one to two positive SLN.
She noted that “mastectomy patients were included in these trials, but they made up a minority” of the populations, ranging from 9% to 18%, “and so controversy remains over the optimal axillary management” in this patient population.
Dr. Kantor said that intraoperative pathology assessment “can help avoid the need to return to the operating room for additional axillary surgery” by checking the SLN at the time.
However, acting on the results during the procedure “does not allow for multidisciplinary discussion” and can mean that patients end up having both ALND and postoperative AxRT.
“This dual approach may result in axillary overtreatment in patients who may otherwise have been eligible for axillary radiation alone,” she underlined.
Moreover, a recent survey of 680 surgeons by the ASBrS found that 52% were performing routine intraoperative pathology assessment of SLN, and 78% of those said they would perform ALND if the results came back positive.
To investigate the impact of intraoperative pathology assessment on axillary management in mastectomy patients who would have been eligible for the AMAROS trial, the team examined data from the U.S. National Cancer Database.
They included cT1-2N0 breast cancer patients who had upfront mastectomy in 2018-2019 and were found to have one to two positive SLN.
They defined intraoperative pathology assessment as:
- “Not done/not acted on” if ALND was either not performed or performed at a later date than the pathology assessment.
- “Done/acted on” if both ALND and the pathology assessment were carried out on the same day.
In addition, AxRT was defined as postmastectomy radiation to the chest wall that included radiation to the draining lymph nodes.
The researchers identified 40,467 patients, of whom 20.3% had one to two positive SLN. Among those, axillary management consisted of observation in 33.2%, ALND in 26.6%, AxRT in 22.2%, and ALND plus AxRT in 18.0%.
Overall, 37.2% of the patients underwent intraoperative pathology and 62.8% did not, 11.8% of whom later returned to the operating room for ALND.
Patients who underwent intraoperative pathology were more likely than those who did not to have cT2 disease (48.0% vs. 44.1%), lympho-vascular invasion (43.4% vs. 37.1%), two positive SLN (26.5% vs. 19.2%), and macrometastasis (87.6% vs. 64.2%, P < .001 for all).
Rates of ALND plus AxRT were significantly higher in patients who had intraoperative pathology done/acted on than in those whom intraoperative pathology was not done/not acted on, at 41.0% vs. 4.9% (P < .001).
Adjusted multivariate analysis indicated that receipt of ALND plus AxRT was significantly associated with intraoperative pathology being done/acted on vs. being not done/acted on, at an odds ratio of 8.99 (P < .001).
There were also significant associations between having both procedures and macrometastasis in the SLN, at an odds ratio vs. micrometastasis of 3.38 (P < .001), and the number of total positive SLN, at odds ratio vs. 1 of 2.14 for two nodes, 3.92 for three nodes, and 5.32 for > three nodes (P < .001 for all).
The researchers also found that lobular tumors on histologic analysis were associated with having ALND plus AxRT, at an odds ratio vs. ductal histology of 1.40 (P < .001).
No funding was declared. Dr. Kantor and Dr. Blair report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ASBRS 2023
Phase 3 trial: Maribavir yields post-transplant benefits
Overall mortality in the 109 patients from these subcohorts from SOLSTICE was lower, compared with mortality reported for similar populations treated with conventional therapies used to treat relapsed or refractory (R/R) CMV, according to findings presented in April at the annual meeting of the European Society for Bone and Marrow Transplantation.
“These results, in addition to the superior efficacy in CMV clearance observed for maribavir in SOLSTICE provide supportive evidence of the potential for the long-term benefit of maribavir treatment for post-transplant CMV infection,” Ishan Hirji, of Takeda Development Center Americas, and colleagues reported during a poster session at the meeting.
A retrospective chart review of the 41 hematopoietic stem cell transplant (HSCT) patients and 68 solid organ transplant (SOT) patients randomized to receive maribavir showed an overall mortality rate of 15.6% at 52 weeks after initiation of treatment with the antiviral agent. Among the HSCT patients, 14 deaths occurred (34.1%), with 8 occurring during the study periods and 6 occurring during follow-up. Among the SOT patients, three deaths occurred (4.4%), all during follow-up chart review.
Causes of death included underlying disease relapse in four patients, infection other than CMV in six patients, and one case each of CMV-related factors, transplant-related factors, acute lymphoblastic leukemia, and septic shock. Causes of death in the SOT patients included one case each of CMV-related factors, anemia, and renal failure.
“No patients had new graft loss or retransplantation during the chart review period,” the investigators noted.
The findings are notable as CMV infection occurs in 30%-70% of HSCT recipients and 16%-56% of SOT recipients and can lead to complications, including transplant failure and death. Reported 1-year mortality rates following standard therapies for CMV range from 31% to 50%, they explained.
Patients in the SOLSTICE trial received 8 weeks of treatment and were followed for 12 additional weeks. CMV clearance at the end of treatment was 55.7% in the maribavir treatment arm versus 23.9% in a control group of patients treated with investigator choice of therapy. As reported by this news organization, the findings formed the basis for U.S. Food and Drug Administration approval of maribavir in November 2021.
The current analysis included a chart review period that started 1 day after the SOLSTICE trial period and continued for 32 additional weeks.
These long-term follow-up data confirm the benefits of maribavir for the treatment of post-transplant CMV, according to the investigators, and findings from a separate study reported at the ESBMT meeting underscore the importance of the durable benefits observed with maribavir treatment.
For that retrospective study, Maria Laura Fox, of Vall d’Hebron Institute of Oncology, Barcelona, and colleagues pooled de-identified data from 250 adult HSCT recipients with R/R CMV who were treated with agents other than maribavir at transplant centers in the United States or Europe. They aimed to “generate real-world evidence on the burden of CMV infection/disease in HSCT recipients who had refractory/resistant CMV or were intolerant to current treatments.”
Nearly 92% of patients received two or more therapies to treat CMV, and 92.2% discontinued treatment or had one or more therapy dose changes or discontinuation, and 42 patients failed to achieve clearance of the CMV index episode.
CMV recurred in 35.2% of patients, and graft failure occurred in 4% of patients, the investigators reported.
All-cause mortality was 56.0%, and mortality at 1 year after identification of R/R disease or treatment intolerance was 45.2%, they noted, adding that the study results “highlight the real-world complexities and high burden of CMV infection for HSCT recipients.”
“With available anti-CMV agents [excluding maribavir], a notable proportion of patients failed to achieve viremia clearance once developing RRI [resistant, refractory, or intolerant] CMV and/or experienced recurrence, and were at risk of adverse outcomes, including myelosuppression and mortality. There is a need for therapies that achieve and maintain CMV clearance with improved safety profiles,” they concluded.
Both studies were funded by Takeda Development Center Americas, the maker of Levtencity. Ms. Hirji is an employee of Takeda and reported stock ownership. Ms. Fox reported relationships with Sierra Oncology, GlaxoSmithKline, Bristol Myers Squibb, Novartis, and AbbVie.
Overall mortality in the 109 patients from these subcohorts from SOLSTICE was lower, compared with mortality reported for similar populations treated with conventional therapies used to treat relapsed or refractory (R/R) CMV, according to findings presented in April at the annual meeting of the European Society for Bone and Marrow Transplantation.
“These results, in addition to the superior efficacy in CMV clearance observed for maribavir in SOLSTICE provide supportive evidence of the potential for the long-term benefit of maribavir treatment for post-transplant CMV infection,” Ishan Hirji, of Takeda Development Center Americas, and colleagues reported during a poster session at the meeting.
A retrospective chart review of the 41 hematopoietic stem cell transplant (HSCT) patients and 68 solid organ transplant (SOT) patients randomized to receive maribavir showed an overall mortality rate of 15.6% at 52 weeks after initiation of treatment with the antiviral agent. Among the HSCT patients, 14 deaths occurred (34.1%), with 8 occurring during the study periods and 6 occurring during follow-up. Among the SOT patients, three deaths occurred (4.4%), all during follow-up chart review.
Causes of death included underlying disease relapse in four patients, infection other than CMV in six patients, and one case each of CMV-related factors, transplant-related factors, acute lymphoblastic leukemia, and septic shock. Causes of death in the SOT patients included one case each of CMV-related factors, anemia, and renal failure.
“No patients had new graft loss or retransplantation during the chart review period,” the investigators noted.
The findings are notable as CMV infection occurs in 30%-70% of HSCT recipients and 16%-56% of SOT recipients and can lead to complications, including transplant failure and death. Reported 1-year mortality rates following standard therapies for CMV range from 31% to 50%, they explained.
Patients in the SOLSTICE trial received 8 weeks of treatment and were followed for 12 additional weeks. CMV clearance at the end of treatment was 55.7% in the maribavir treatment arm versus 23.9% in a control group of patients treated with investigator choice of therapy. As reported by this news organization, the findings formed the basis for U.S. Food and Drug Administration approval of maribavir in November 2021.
The current analysis included a chart review period that started 1 day after the SOLSTICE trial period and continued for 32 additional weeks.
These long-term follow-up data confirm the benefits of maribavir for the treatment of post-transplant CMV, according to the investigators, and findings from a separate study reported at the ESBMT meeting underscore the importance of the durable benefits observed with maribavir treatment.
For that retrospective study, Maria Laura Fox, of Vall d’Hebron Institute of Oncology, Barcelona, and colleagues pooled de-identified data from 250 adult HSCT recipients with R/R CMV who were treated with agents other than maribavir at transplant centers in the United States or Europe. They aimed to “generate real-world evidence on the burden of CMV infection/disease in HSCT recipients who had refractory/resistant CMV or were intolerant to current treatments.”
Nearly 92% of patients received two or more therapies to treat CMV, and 92.2% discontinued treatment or had one or more therapy dose changes or discontinuation, and 42 patients failed to achieve clearance of the CMV index episode.
CMV recurred in 35.2% of patients, and graft failure occurred in 4% of patients, the investigators reported.
All-cause mortality was 56.0%, and mortality at 1 year after identification of R/R disease or treatment intolerance was 45.2%, they noted, adding that the study results “highlight the real-world complexities and high burden of CMV infection for HSCT recipients.”
“With available anti-CMV agents [excluding maribavir], a notable proportion of patients failed to achieve viremia clearance once developing RRI [resistant, refractory, or intolerant] CMV and/or experienced recurrence, and were at risk of adverse outcomes, including myelosuppression and mortality. There is a need for therapies that achieve and maintain CMV clearance with improved safety profiles,” they concluded.
Both studies were funded by Takeda Development Center Americas, the maker of Levtencity. Ms. Hirji is an employee of Takeda and reported stock ownership. Ms. Fox reported relationships with Sierra Oncology, GlaxoSmithKline, Bristol Myers Squibb, Novartis, and AbbVie.
Overall mortality in the 109 patients from these subcohorts from SOLSTICE was lower, compared with mortality reported for similar populations treated with conventional therapies used to treat relapsed or refractory (R/R) CMV, according to findings presented in April at the annual meeting of the European Society for Bone and Marrow Transplantation.
“These results, in addition to the superior efficacy in CMV clearance observed for maribavir in SOLSTICE provide supportive evidence of the potential for the long-term benefit of maribavir treatment for post-transplant CMV infection,” Ishan Hirji, of Takeda Development Center Americas, and colleagues reported during a poster session at the meeting.
A retrospective chart review of the 41 hematopoietic stem cell transplant (HSCT) patients and 68 solid organ transplant (SOT) patients randomized to receive maribavir showed an overall mortality rate of 15.6% at 52 weeks after initiation of treatment with the antiviral agent. Among the HSCT patients, 14 deaths occurred (34.1%), with 8 occurring during the study periods and 6 occurring during follow-up. Among the SOT patients, three deaths occurred (4.4%), all during follow-up chart review.
Causes of death included underlying disease relapse in four patients, infection other than CMV in six patients, and one case each of CMV-related factors, transplant-related factors, acute lymphoblastic leukemia, and septic shock. Causes of death in the SOT patients included one case each of CMV-related factors, anemia, and renal failure.
“No patients had new graft loss or retransplantation during the chart review period,” the investigators noted.
The findings are notable as CMV infection occurs in 30%-70% of HSCT recipients and 16%-56% of SOT recipients and can lead to complications, including transplant failure and death. Reported 1-year mortality rates following standard therapies for CMV range from 31% to 50%, they explained.
Patients in the SOLSTICE trial received 8 weeks of treatment and were followed for 12 additional weeks. CMV clearance at the end of treatment was 55.7% in the maribavir treatment arm versus 23.9% in a control group of patients treated with investigator choice of therapy. As reported by this news organization, the findings formed the basis for U.S. Food and Drug Administration approval of maribavir in November 2021.
The current analysis included a chart review period that started 1 day after the SOLSTICE trial period and continued for 32 additional weeks.
These long-term follow-up data confirm the benefits of maribavir for the treatment of post-transplant CMV, according to the investigators, and findings from a separate study reported at the ESBMT meeting underscore the importance of the durable benefits observed with maribavir treatment.
For that retrospective study, Maria Laura Fox, of Vall d’Hebron Institute of Oncology, Barcelona, and colleagues pooled de-identified data from 250 adult HSCT recipients with R/R CMV who were treated with agents other than maribavir at transplant centers in the United States or Europe. They aimed to “generate real-world evidence on the burden of CMV infection/disease in HSCT recipients who had refractory/resistant CMV or were intolerant to current treatments.”
Nearly 92% of patients received two or more therapies to treat CMV, and 92.2% discontinued treatment or had one or more therapy dose changes or discontinuation, and 42 patients failed to achieve clearance of the CMV index episode.
CMV recurred in 35.2% of patients, and graft failure occurred in 4% of patients, the investigators reported.
All-cause mortality was 56.0%, and mortality at 1 year after identification of R/R disease or treatment intolerance was 45.2%, they noted, adding that the study results “highlight the real-world complexities and high burden of CMV infection for HSCT recipients.”
“With available anti-CMV agents [excluding maribavir], a notable proportion of patients failed to achieve viremia clearance once developing RRI [resistant, refractory, or intolerant] CMV and/or experienced recurrence, and were at risk of adverse outcomes, including myelosuppression and mortality. There is a need for therapies that achieve and maintain CMV clearance with improved safety profiles,” they concluded.
Both studies were funded by Takeda Development Center Americas, the maker of Levtencity. Ms. Hirji is an employee of Takeda and reported stock ownership. Ms. Fox reported relationships with Sierra Oncology, GlaxoSmithKline, Bristol Myers Squibb, Novartis, and AbbVie.
FROM ESBMT 2023
Stroke scale cutoff might not be ideal guide for ordering CTA and detecting large vessel occlusions
BOSTON – (LVO), according to large body of data presented at the 2023 annual meeting of the American Academy of Neurology.
If the goal is not to miss any LVOs, there is no NIHSS score below which these do not occur, according to Theresa Sevilis, DO, regional medical director, TeleSpecialists, Fort Myers, Fla.
For example, her evaluation of a large and nationally representative dataset shows that more than 10% of the LVOs eventually identified and accepted for intervention would be missed with a cutoff of NIHSS score of 6 or higher. Moving the cutoff NIHSS score to 4 or greater, 6% of LVOs among the 23,166 strokes evaluated would have gone undetected.
“The current guidelines do not address low NIHSS score largely due to a paucity of data,” according to Dr. Sevilis, who showed data indicating that there is great variation among institutions in regard to ordering computed tomography angiography (CTA). She indicated that CTA is the current imaging standard for detecting LVO.
Large prospective dataset
The data for this study were derived from the TeleCare database, which captures acute stroke consultations in the emergency departments in 227 facilities in 27 states. Stroke consultations over a 6-month period from July through December 2021 were evaluated. The prospectively collected data were subjected to a multivariate analysis to determine the odds ratio for a CTA performed and LVO found at each NIHSS score of 0 to 5. Scores 6 or above served as the reference.
“Only consults performed within 24 hours [of presentation] were included,” Dr. Sevilis said.
After excluding cases in which no NIHSS score was captured, which represented less than 1% of cases, more than 10,500 cases underwent CTA, providing a rate of 45.5%. The rate of CTA for the whole dataset was 45.5%. Of the study population, 24.6% had a NIHSS score of 6 or above.
“When you are discussing when to perform CTA in patients with a low NIHSS score, you are discussing the majority of patients,” Dr. Sevilis said.
Of those with a NIHSS stroke of 6 or below, 28.2% had a score of 0. Not surprisingly, these were the least likely to have a CTA performed on the basis of an odds ratio of 0.14 and the least likely to have a LVO detected (OR, 0.1). With the exception of a NIHSS stroke score of 1, the likelihood of CTA and LVO climbed incrementally with higher stroke scores. These odds ratios were, respectively, 0.16 and 0.09 for a score of 1; 0.27 and 0.16 for a score of 2; 0.33 and 0.14 for a score of 3; 0.49 and 0.24 for a score of 4; and 0.71 and 0.27 for a score of 5.
In the group with NIHSS score of 6 or above, 24.1% were found to have an LVO. Of these, the proportion accepted for a mechanical thrombectomy was less than half. The intervention acceptance rate for mechanical intervention among LVOs in patients with lower NIHSS scores again fell incrementally by score. The acceptance rate was about 35% among LVO patients with a NIHSS score of 3 or 4 and 25% for those with a score of 0-2.
The interpretation of these data “depends on goals,” Dr. Sevilis said. “If the goal is to not miss a single LVO, then it is important to consider the balance between benefits and risks.”
No consistent cutoff
In participating facilities, the protocol for considering CTA to detect and treat LVOs ranges from neurologist choice to cutoffs of NIHSS scores of 2, 4, and 6, according to Dr. Sevilis. Where the data suggest that a cutoff of 4 or above might be reasonable, she said that NIHSS scoring is not a useful tool for those “who do not want to miss any LVOs.”
These data are based on emergency room stroke consultations and not on confirmed strokes,” Dr. Sevilis emphasized. Indeed, she noted that the final discharge diagnosis was not available. Recognizing that the analysis was not performed on a population with confirmed strokes is particularly important for understanding the limited rate of CTAs performed even in those with relatively high NIHSS scores. She noted this could be explained by many different reasons, including suspicion of hemorrhage or clinical features that took the workup in a different direction.
Reconsidering protocols
Based on the large sample size, Dr. Sevilis contended that it is likely that these data are representative, but she considers this study a first step toward considering protocols and developing guidelines for addressing stroke alerts in the emergency department.
A more important step will be ongoing trials designed specifically to generate data to answer this question. Pascal Jabbour, MD, chief of the division of neurovascular and endovascular neurosurgery, Thomas Jefferson University Hospitals, Philadelphia, is participating in one of these trials. He agreed with the premise that better evidence-based criteria are needed when evaluating acute stroke patients with a potential LVO.
The trial in which he is a coinvestigator, called ENDOLOW, is testing the hypothesis that outcomes will be better if acute stroke patients with a LVO and a low baseline NIHSS score (< 5) are treated with immediate thrombectomy rather than medical management. If this hypothesis is confirmed in the randomized ENDOLOW, it will provide an evidence basis for an approach already being practiced at some centers.
“There should be a very low threshold for CTA,” said Dr. Jabbour in an interview. This imaging “takes less than 2 minutes and it can provide the basis for a life-saving endovascular thrombectomy if a LVO is found.”
It is already well known that LVO is not restricted only to patients with an elevated NIHSS score, he said.
For determining whether to order a CTA, “I do not agree with NIHSS score of 6 or above. There is no absolute number below which risk of missing a LVO is eliminated,” Dr. Jabbour said. He also argued against relying on NIHSS score without considering other clinical features, particularly cortical signs, which should raise suspicion of a LVO regardless of NIHSS score.
One problem is that NIHSS scores are not static. Decompensation can be rapid with the NIHSS score quickly climbing. When this happens, the delay in treatment might lead to a preventable adverse outcome.
“There is a change in the paradigm now that we have more evidence of a benefit from aggressive treatment in the right candidates,” according to Dr. Jabbour, referring to the recently published SELECT2 trial. In that trial, on which Dr. Jabbour served as a coauthor, patients with LVO and large territory infarct were randomized to thrombectomy or medical care within 24 hours of a stroke. It was stopped early for efficacy because of the increased functional independence (20% vs. 7%) in the surgical intervention group.
If the ongoing trials establish better criteria for ruling in or out the presence of LVO in patients with acute stroke, Dr. Jabbour predicted that guidelines will be written to standardize practice.
Dr. Sevilis reports no potential conflicts of interest. Dr. Jabbour has financial relationships with Cerenovus, Medtronic, and Microvention.
BOSTON – (LVO), according to large body of data presented at the 2023 annual meeting of the American Academy of Neurology.
If the goal is not to miss any LVOs, there is no NIHSS score below which these do not occur, according to Theresa Sevilis, DO, regional medical director, TeleSpecialists, Fort Myers, Fla.
For example, her evaluation of a large and nationally representative dataset shows that more than 10% of the LVOs eventually identified and accepted for intervention would be missed with a cutoff of NIHSS score of 6 or higher. Moving the cutoff NIHSS score to 4 or greater, 6% of LVOs among the 23,166 strokes evaluated would have gone undetected.
“The current guidelines do not address low NIHSS score largely due to a paucity of data,” according to Dr. Sevilis, who showed data indicating that there is great variation among institutions in regard to ordering computed tomography angiography (CTA). She indicated that CTA is the current imaging standard for detecting LVO.
Large prospective dataset
The data for this study were derived from the TeleCare database, which captures acute stroke consultations in the emergency departments in 227 facilities in 27 states. Stroke consultations over a 6-month period from July through December 2021 were evaluated. The prospectively collected data were subjected to a multivariate analysis to determine the odds ratio for a CTA performed and LVO found at each NIHSS score of 0 to 5. Scores 6 or above served as the reference.
“Only consults performed within 24 hours [of presentation] were included,” Dr. Sevilis said.
After excluding cases in which no NIHSS score was captured, which represented less than 1% of cases, more than 10,500 cases underwent CTA, providing a rate of 45.5%. The rate of CTA for the whole dataset was 45.5%. Of the study population, 24.6% had a NIHSS score of 6 or above.
“When you are discussing when to perform CTA in patients with a low NIHSS score, you are discussing the majority of patients,” Dr. Sevilis said.
Of those with a NIHSS stroke of 6 or below, 28.2% had a score of 0. Not surprisingly, these were the least likely to have a CTA performed on the basis of an odds ratio of 0.14 and the least likely to have a LVO detected (OR, 0.1). With the exception of a NIHSS stroke score of 1, the likelihood of CTA and LVO climbed incrementally with higher stroke scores. These odds ratios were, respectively, 0.16 and 0.09 for a score of 1; 0.27 and 0.16 for a score of 2; 0.33 and 0.14 for a score of 3; 0.49 and 0.24 for a score of 4; and 0.71 and 0.27 for a score of 5.
In the group with NIHSS score of 6 or above, 24.1% were found to have an LVO. Of these, the proportion accepted for a mechanical thrombectomy was less than half. The intervention acceptance rate for mechanical intervention among LVOs in patients with lower NIHSS scores again fell incrementally by score. The acceptance rate was about 35% among LVO patients with a NIHSS score of 3 or 4 and 25% for those with a score of 0-2.
The interpretation of these data “depends on goals,” Dr. Sevilis said. “If the goal is to not miss a single LVO, then it is important to consider the balance between benefits and risks.”
No consistent cutoff
In participating facilities, the protocol for considering CTA to detect and treat LVOs ranges from neurologist choice to cutoffs of NIHSS scores of 2, 4, and 6, according to Dr. Sevilis. Where the data suggest that a cutoff of 4 or above might be reasonable, she said that NIHSS scoring is not a useful tool for those “who do not want to miss any LVOs.”
These data are based on emergency room stroke consultations and not on confirmed strokes,” Dr. Sevilis emphasized. Indeed, she noted that the final discharge diagnosis was not available. Recognizing that the analysis was not performed on a population with confirmed strokes is particularly important for understanding the limited rate of CTAs performed even in those with relatively high NIHSS scores. She noted this could be explained by many different reasons, including suspicion of hemorrhage or clinical features that took the workup in a different direction.
Reconsidering protocols
Based on the large sample size, Dr. Sevilis contended that it is likely that these data are representative, but she considers this study a first step toward considering protocols and developing guidelines for addressing stroke alerts in the emergency department.
A more important step will be ongoing trials designed specifically to generate data to answer this question. Pascal Jabbour, MD, chief of the division of neurovascular and endovascular neurosurgery, Thomas Jefferson University Hospitals, Philadelphia, is participating in one of these trials. He agreed with the premise that better evidence-based criteria are needed when evaluating acute stroke patients with a potential LVO.
The trial in which he is a coinvestigator, called ENDOLOW, is testing the hypothesis that outcomes will be better if acute stroke patients with a LVO and a low baseline NIHSS score (< 5) are treated with immediate thrombectomy rather than medical management. If this hypothesis is confirmed in the randomized ENDOLOW, it will provide an evidence basis for an approach already being practiced at some centers.
“There should be a very low threshold for CTA,” said Dr. Jabbour in an interview. This imaging “takes less than 2 minutes and it can provide the basis for a life-saving endovascular thrombectomy if a LVO is found.”
It is already well known that LVO is not restricted only to patients with an elevated NIHSS score, he said.
For determining whether to order a CTA, “I do not agree with NIHSS score of 6 or above. There is no absolute number below which risk of missing a LVO is eliminated,” Dr. Jabbour said. He also argued against relying on NIHSS score without considering other clinical features, particularly cortical signs, which should raise suspicion of a LVO regardless of NIHSS score.
One problem is that NIHSS scores are not static. Decompensation can be rapid with the NIHSS score quickly climbing. When this happens, the delay in treatment might lead to a preventable adverse outcome.
“There is a change in the paradigm now that we have more evidence of a benefit from aggressive treatment in the right candidates,” according to Dr. Jabbour, referring to the recently published SELECT2 trial. In that trial, on which Dr. Jabbour served as a coauthor, patients with LVO and large territory infarct were randomized to thrombectomy or medical care within 24 hours of a stroke. It was stopped early for efficacy because of the increased functional independence (20% vs. 7%) in the surgical intervention group.
If the ongoing trials establish better criteria for ruling in or out the presence of LVO in patients with acute stroke, Dr. Jabbour predicted that guidelines will be written to standardize practice.
Dr. Sevilis reports no potential conflicts of interest. Dr. Jabbour has financial relationships with Cerenovus, Medtronic, and Microvention.
BOSTON – (LVO), according to large body of data presented at the 2023 annual meeting of the American Academy of Neurology.
If the goal is not to miss any LVOs, there is no NIHSS score below which these do not occur, according to Theresa Sevilis, DO, regional medical director, TeleSpecialists, Fort Myers, Fla.
For example, her evaluation of a large and nationally representative dataset shows that more than 10% of the LVOs eventually identified and accepted for intervention would be missed with a cutoff of NIHSS score of 6 or higher. Moving the cutoff NIHSS score to 4 or greater, 6% of LVOs among the 23,166 strokes evaluated would have gone undetected.
“The current guidelines do not address low NIHSS score largely due to a paucity of data,” according to Dr. Sevilis, who showed data indicating that there is great variation among institutions in regard to ordering computed tomography angiography (CTA). She indicated that CTA is the current imaging standard for detecting LVO.
Large prospective dataset
The data for this study were derived from the TeleCare database, which captures acute stroke consultations in the emergency departments in 227 facilities in 27 states. Stroke consultations over a 6-month period from July through December 2021 were evaluated. The prospectively collected data were subjected to a multivariate analysis to determine the odds ratio for a CTA performed and LVO found at each NIHSS score of 0 to 5. Scores 6 or above served as the reference.
“Only consults performed within 24 hours [of presentation] were included,” Dr. Sevilis said.
After excluding cases in which no NIHSS score was captured, which represented less than 1% of cases, more than 10,500 cases underwent CTA, providing a rate of 45.5%. The rate of CTA for the whole dataset was 45.5%. Of the study population, 24.6% had a NIHSS score of 6 or above.
“When you are discussing when to perform CTA in patients with a low NIHSS score, you are discussing the majority of patients,” Dr. Sevilis said.
Of those with a NIHSS stroke of 6 or below, 28.2% had a score of 0. Not surprisingly, these were the least likely to have a CTA performed on the basis of an odds ratio of 0.14 and the least likely to have a LVO detected (OR, 0.1). With the exception of a NIHSS stroke score of 1, the likelihood of CTA and LVO climbed incrementally with higher stroke scores. These odds ratios were, respectively, 0.16 and 0.09 for a score of 1; 0.27 and 0.16 for a score of 2; 0.33 and 0.14 for a score of 3; 0.49 and 0.24 for a score of 4; and 0.71 and 0.27 for a score of 5.
In the group with NIHSS score of 6 or above, 24.1% were found to have an LVO. Of these, the proportion accepted for a mechanical thrombectomy was less than half. The intervention acceptance rate for mechanical intervention among LVOs in patients with lower NIHSS scores again fell incrementally by score. The acceptance rate was about 35% among LVO patients with a NIHSS score of 3 or 4 and 25% for those with a score of 0-2.
The interpretation of these data “depends on goals,” Dr. Sevilis said. “If the goal is to not miss a single LVO, then it is important to consider the balance between benefits and risks.”
No consistent cutoff
In participating facilities, the protocol for considering CTA to detect and treat LVOs ranges from neurologist choice to cutoffs of NIHSS scores of 2, 4, and 6, according to Dr. Sevilis. Where the data suggest that a cutoff of 4 or above might be reasonable, she said that NIHSS scoring is not a useful tool for those “who do not want to miss any LVOs.”
These data are based on emergency room stroke consultations and not on confirmed strokes,” Dr. Sevilis emphasized. Indeed, she noted that the final discharge diagnosis was not available. Recognizing that the analysis was not performed on a population with confirmed strokes is particularly important for understanding the limited rate of CTAs performed even in those with relatively high NIHSS scores. She noted this could be explained by many different reasons, including suspicion of hemorrhage or clinical features that took the workup in a different direction.
Reconsidering protocols
Based on the large sample size, Dr. Sevilis contended that it is likely that these data are representative, but she considers this study a first step toward considering protocols and developing guidelines for addressing stroke alerts in the emergency department.
A more important step will be ongoing trials designed specifically to generate data to answer this question. Pascal Jabbour, MD, chief of the division of neurovascular and endovascular neurosurgery, Thomas Jefferson University Hospitals, Philadelphia, is participating in one of these trials. He agreed with the premise that better evidence-based criteria are needed when evaluating acute stroke patients with a potential LVO.
The trial in which he is a coinvestigator, called ENDOLOW, is testing the hypothesis that outcomes will be better if acute stroke patients with a LVO and a low baseline NIHSS score (< 5) are treated with immediate thrombectomy rather than medical management. If this hypothesis is confirmed in the randomized ENDOLOW, it will provide an evidence basis for an approach already being practiced at some centers.
“There should be a very low threshold for CTA,” said Dr. Jabbour in an interview. This imaging “takes less than 2 minutes and it can provide the basis for a life-saving endovascular thrombectomy if a LVO is found.”
It is already well known that LVO is not restricted only to patients with an elevated NIHSS score, he said.
For determining whether to order a CTA, “I do not agree with NIHSS score of 6 or above. There is no absolute number below which risk of missing a LVO is eliminated,” Dr. Jabbour said. He also argued against relying on NIHSS score without considering other clinical features, particularly cortical signs, which should raise suspicion of a LVO regardless of NIHSS score.
One problem is that NIHSS scores are not static. Decompensation can be rapid with the NIHSS score quickly climbing. When this happens, the delay in treatment might lead to a preventable adverse outcome.
“There is a change in the paradigm now that we have more evidence of a benefit from aggressive treatment in the right candidates,” according to Dr. Jabbour, referring to the recently published SELECT2 trial. In that trial, on which Dr. Jabbour served as a coauthor, patients with LVO and large territory infarct were randomized to thrombectomy or medical care within 24 hours of a stroke. It was stopped early for efficacy because of the increased functional independence (20% vs. 7%) in the surgical intervention group.
If the ongoing trials establish better criteria for ruling in or out the presence of LVO in patients with acute stroke, Dr. Jabbour predicted that guidelines will be written to standardize practice.
Dr. Sevilis reports no potential conflicts of interest. Dr. Jabbour has financial relationships with Cerenovus, Medtronic, and Microvention.
FROM AAN 2023
Expert discusses which diets are best, based on the evidence
according to a speaker at the annual meeting of the American College of Physicians.
“Evidence from studies can help clinicians and their patients develop a successful dietary management plan and achieve optimal health,” said internist Michelle Hauser, MD, clinical associate professor at Stanford (Calif.) University. She also discussed evidence-based techniques to support patients in maintaining dietary modifications.
Predominantly plant‐based diets
Popular predominantly plant‐based diets include a Mediterranean diet, healthy vegetarian diet, predominantly whole-food plant‐based (WFPB) diet, and a dietary approach to stop hypertension (DASH).
The DASH diet was originally designed to help patients manage their blood pressure, but evidence suggests that it also can help adults with obesity lose weight. In contrast to the DASH diet, the Mediterranean diet is not low-fat and not very restrictive. Yet the evidence suggests that the Mediterranean diet is not only helpful for losing weight but also can reduce the risk of various chronic diseases, including obesity, type 2 diabetes, cardiovascular disease (CVD), and cancer, Dr. Hauser said. In addition, data suggest that the Mediterranean diet may reduce the risk of all-cause mortality and lower the levels of cholesterol.
“I like to highlight all these protective effects to my patients, because even if their goal is to lose weight, knowing that hard work pays off in additional ways can keep them motivated,” Dr. Hauser stated.
A healthy vegetarian diet and a WFPB diet are similar, and both are helpful in weight loss and management of total cholesterol and LDL‐C levels. Furthermore, healthy vegetarian and WFPB diets may reduce the risk of type 2 diabetes, CVD, and some cancers. Cohort study data suggest that progressively more vegetarian diets are associated with lower BMIs.
“My interpretation of these data is that predominantly plant-based diets rich in whole foods are healthful and can be done in a way that is sustainable for most,” said Dr. Hauser. However, this generally requires a lot of support at the outset to address gaps in knowledge, skills, and other potential barriers.
For example, she referred one obese patient at risk of diabetes and cardiovascular disease to a registered dietitian to develop a dietary plan. The patient also attended a behavioral medicine weight management program to learn strategies such as using smaller plates, and his family attended a healthy cooking class together to improve meal planning and cooking skills.
Time‐restricted feeding
There are numerous variations of time-restricted feeding, commonly referred to as intermittent fasting, but the principles are similar – limiting food intake to a specific window of time each day or week.
Although some studies have shown that time-restricted feeding may help patients reduce adiposity and improve lipid markers, most studies comparing time-restricted feeding to a calorie-restricted diet have shown little to no difference in weight-related outcomes, Dr. Hauser said.
These data suggest that time-restricted feeding may help patients with weight loss only if time restriction helps them reduce calorie intake. She also warned that time-restrictive feeding might cause late-night cravings and might not be helpful in individuals prone to food cravings.
Low‐carbohydrate and ketogenic diets
Losing muscle mass can prevent some people from dieting, but evidence suggests that a high-fat, very low-carbohydrate diet – also called a ketogenic diet – may help patients reduce weight and fat mass while preserving fat‐free mass, Dr. Hauser said.
The evidence regarding the usefulness of a low-carbohydrate (non-keto) diet is less clear because most studies compared it to a low-fat diet, and these two diets might lead to a similar extent of weight loss.
Rating the level of scientific evidence behind different diet options
Nutrition studies do no provide the same level of evidence as drug studies, said Dr. Hauser, because it is easier to conduct a randomized controlled trial of a drug versus placebo. Diets have many more variables, and it also takes much longer to observe most outcomes of a dietary change.
In addition, clinical trials of dietary interventions are typically short and focus on disease markers such as serum lipids and hemoglobin A1c levels. To obtain reliable information on the usefulness of a diet, researchers need to collect detailed health and lifestyle information from hundreds of thousands of people over several decades, which is not always feasible. “This is why meta-analyses of pooled dietary study data are more likely to yield dependable findings,” she noted.
Getting to know patients is essential to help them maintain diet modifications
When developing a diet plan for a patient, it is important to consider the sustainability of a dietary pattern. “The benefits of any healthy dietary change will only last as long as they can be maintained,” said Dr. Hauser. “Counseling someone on choosing an appropriate long-term dietary pattern requires getting to know them – taste preferences, food traditions, barriers, facilitators, food access, and time and cost restrictions.”
In an interview after the session, David Bittleman, MD, an internist at Veterans Affairs San Diego Health Care System, agreed that getting to know patients is essential for successfully advising them on diet.
“I always start developing a diet plan by trying to find out what [a patient’s] diet is like and what their goals are. I need to know what they are already doing in order to make suggestions about what they can do to make their diet healthier,” he said.
When asked about her approach to supporting patients in the long term, Dr. Hauser said that she recommends sequential, gradual changes. Dr. Hauser added that she suggests her patients prioritize implementing dietary changes that they are confident they can maintain.
Dr. Hauser and Dr. Bittleman report no relevant financial relationships.
according to a speaker at the annual meeting of the American College of Physicians.
“Evidence from studies can help clinicians and their patients develop a successful dietary management plan and achieve optimal health,” said internist Michelle Hauser, MD, clinical associate professor at Stanford (Calif.) University. She also discussed evidence-based techniques to support patients in maintaining dietary modifications.
Predominantly plant‐based diets
Popular predominantly plant‐based diets include a Mediterranean diet, healthy vegetarian diet, predominantly whole-food plant‐based (WFPB) diet, and a dietary approach to stop hypertension (DASH).
The DASH diet was originally designed to help patients manage their blood pressure, but evidence suggests that it also can help adults with obesity lose weight. In contrast to the DASH diet, the Mediterranean diet is not low-fat and not very restrictive. Yet the evidence suggests that the Mediterranean diet is not only helpful for losing weight but also can reduce the risk of various chronic diseases, including obesity, type 2 diabetes, cardiovascular disease (CVD), and cancer, Dr. Hauser said. In addition, data suggest that the Mediterranean diet may reduce the risk of all-cause mortality and lower the levels of cholesterol.
“I like to highlight all these protective effects to my patients, because even if their goal is to lose weight, knowing that hard work pays off in additional ways can keep them motivated,” Dr. Hauser stated.
A healthy vegetarian diet and a WFPB diet are similar, and both are helpful in weight loss and management of total cholesterol and LDL‐C levels. Furthermore, healthy vegetarian and WFPB diets may reduce the risk of type 2 diabetes, CVD, and some cancers. Cohort study data suggest that progressively more vegetarian diets are associated with lower BMIs.
“My interpretation of these data is that predominantly plant-based diets rich in whole foods are healthful and can be done in a way that is sustainable for most,” said Dr. Hauser. However, this generally requires a lot of support at the outset to address gaps in knowledge, skills, and other potential barriers.
For example, she referred one obese patient at risk of diabetes and cardiovascular disease to a registered dietitian to develop a dietary plan. The patient also attended a behavioral medicine weight management program to learn strategies such as using smaller plates, and his family attended a healthy cooking class together to improve meal planning and cooking skills.
Time‐restricted feeding
There are numerous variations of time-restricted feeding, commonly referred to as intermittent fasting, but the principles are similar – limiting food intake to a specific window of time each day or week.
Although some studies have shown that time-restricted feeding may help patients reduce adiposity and improve lipid markers, most studies comparing time-restricted feeding to a calorie-restricted diet have shown little to no difference in weight-related outcomes, Dr. Hauser said.
These data suggest that time-restricted feeding may help patients with weight loss only if time restriction helps them reduce calorie intake. She also warned that time-restrictive feeding might cause late-night cravings and might not be helpful in individuals prone to food cravings.
Low‐carbohydrate and ketogenic diets
Losing muscle mass can prevent some people from dieting, but evidence suggests that a high-fat, very low-carbohydrate diet – also called a ketogenic diet – may help patients reduce weight and fat mass while preserving fat‐free mass, Dr. Hauser said.
The evidence regarding the usefulness of a low-carbohydrate (non-keto) diet is less clear because most studies compared it to a low-fat diet, and these two diets might lead to a similar extent of weight loss.
Rating the level of scientific evidence behind different diet options
Nutrition studies do no provide the same level of evidence as drug studies, said Dr. Hauser, because it is easier to conduct a randomized controlled trial of a drug versus placebo. Diets have many more variables, and it also takes much longer to observe most outcomes of a dietary change.
In addition, clinical trials of dietary interventions are typically short and focus on disease markers such as serum lipids and hemoglobin A1c levels. To obtain reliable information on the usefulness of a diet, researchers need to collect detailed health and lifestyle information from hundreds of thousands of people over several decades, which is not always feasible. “This is why meta-analyses of pooled dietary study data are more likely to yield dependable findings,” she noted.
Getting to know patients is essential to help them maintain diet modifications
When developing a diet plan for a patient, it is important to consider the sustainability of a dietary pattern. “The benefits of any healthy dietary change will only last as long as they can be maintained,” said Dr. Hauser. “Counseling someone on choosing an appropriate long-term dietary pattern requires getting to know them – taste preferences, food traditions, barriers, facilitators, food access, and time and cost restrictions.”
In an interview after the session, David Bittleman, MD, an internist at Veterans Affairs San Diego Health Care System, agreed that getting to know patients is essential for successfully advising them on diet.
“I always start developing a diet plan by trying to find out what [a patient’s] diet is like and what their goals are. I need to know what they are already doing in order to make suggestions about what they can do to make their diet healthier,” he said.
When asked about her approach to supporting patients in the long term, Dr. Hauser said that she recommends sequential, gradual changes. Dr. Hauser added that she suggests her patients prioritize implementing dietary changes that they are confident they can maintain.
Dr. Hauser and Dr. Bittleman report no relevant financial relationships.
according to a speaker at the annual meeting of the American College of Physicians.
“Evidence from studies can help clinicians and their patients develop a successful dietary management plan and achieve optimal health,” said internist Michelle Hauser, MD, clinical associate professor at Stanford (Calif.) University. She also discussed evidence-based techniques to support patients in maintaining dietary modifications.
Predominantly plant‐based diets
Popular predominantly plant‐based diets include a Mediterranean diet, healthy vegetarian diet, predominantly whole-food plant‐based (WFPB) diet, and a dietary approach to stop hypertension (DASH).
The DASH diet was originally designed to help patients manage their blood pressure, but evidence suggests that it also can help adults with obesity lose weight. In contrast to the DASH diet, the Mediterranean diet is not low-fat and not very restrictive. Yet the evidence suggests that the Mediterranean diet is not only helpful for losing weight but also can reduce the risk of various chronic diseases, including obesity, type 2 diabetes, cardiovascular disease (CVD), and cancer, Dr. Hauser said. In addition, data suggest that the Mediterranean diet may reduce the risk of all-cause mortality and lower the levels of cholesterol.
“I like to highlight all these protective effects to my patients, because even if their goal is to lose weight, knowing that hard work pays off in additional ways can keep them motivated,” Dr. Hauser stated.
A healthy vegetarian diet and a WFPB diet are similar, and both are helpful in weight loss and management of total cholesterol and LDL‐C levels. Furthermore, healthy vegetarian and WFPB diets may reduce the risk of type 2 diabetes, CVD, and some cancers. Cohort study data suggest that progressively more vegetarian diets are associated with lower BMIs.
“My interpretation of these data is that predominantly plant-based diets rich in whole foods are healthful and can be done in a way that is sustainable for most,” said Dr. Hauser. However, this generally requires a lot of support at the outset to address gaps in knowledge, skills, and other potential barriers.
For example, she referred one obese patient at risk of diabetes and cardiovascular disease to a registered dietitian to develop a dietary plan. The patient also attended a behavioral medicine weight management program to learn strategies such as using smaller plates, and his family attended a healthy cooking class together to improve meal planning and cooking skills.
Time‐restricted feeding
There are numerous variations of time-restricted feeding, commonly referred to as intermittent fasting, but the principles are similar – limiting food intake to a specific window of time each day or week.
Although some studies have shown that time-restricted feeding may help patients reduce adiposity and improve lipid markers, most studies comparing time-restricted feeding to a calorie-restricted diet have shown little to no difference in weight-related outcomes, Dr. Hauser said.
These data suggest that time-restricted feeding may help patients with weight loss only if time restriction helps them reduce calorie intake. She also warned that time-restrictive feeding might cause late-night cravings and might not be helpful in individuals prone to food cravings.
Low‐carbohydrate and ketogenic diets
Losing muscle mass can prevent some people from dieting, but evidence suggests that a high-fat, very low-carbohydrate diet – also called a ketogenic diet – may help patients reduce weight and fat mass while preserving fat‐free mass, Dr. Hauser said.
The evidence regarding the usefulness of a low-carbohydrate (non-keto) diet is less clear because most studies compared it to a low-fat diet, and these two diets might lead to a similar extent of weight loss.
Rating the level of scientific evidence behind different diet options
Nutrition studies do no provide the same level of evidence as drug studies, said Dr. Hauser, because it is easier to conduct a randomized controlled trial of a drug versus placebo. Diets have many more variables, and it also takes much longer to observe most outcomes of a dietary change.
In addition, clinical trials of dietary interventions are typically short and focus on disease markers such as serum lipids and hemoglobin A1c levels. To obtain reliable information on the usefulness of a diet, researchers need to collect detailed health and lifestyle information from hundreds of thousands of people over several decades, which is not always feasible. “This is why meta-analyses of pooled dietary study data are more likely to yield dependable findings,” she noted.
Getting to know patients is essential to help them maintain diet modifications
When developing a diet plan for a patient, it is important to consider the sustainability of a dietary pattern. “The benefits of any healthy dietary change will only last as long as they can be maintained,” said Dr. Hauser. “Counseling someone on choosing an appropriate long-term dietary pattern requires getting to know them – taste preferences, food traditions, barriers, facilitators, food access, and time and cost restrictions.”
In an interview after the session, David Bittleman, MD, an internist at Veterans Affairs San Diego Health Care System, agreed that getting to know patients is essential for successfully advising them on diet.
“I always start developing a diet plan by trying to find out what [a patient’s] diet is like and what their goals are. I need to know what they are already doing in order to make suggestions about what they can do to make their diet healthier,” he said.
When asked about her approach to supporting patients in the long term, Dr. Hauser said that she recommends sequential, gradual changes. Dr. Hauser added that she suggests her patients prioritize implementing dietary changes that they are confident they can maintain.
Dr. Hauser and Dr. Bittleman report no relevant financial relationships.
AT INTERNAL MEDICINE 2023
Long-term impact of childhood trauma explained
WASHINGTON –
“We already knew childhood trauma is associated with the later development of depressive and anxiety disorders, but it’s been unclear what makes sufferers of early trauma more likely to develop these psychiatric conditions,” study investigator Erika Kuzminskaite, PhD candidate, department of psychiatry, Amsterdam University Medical Center (UMC), the Netherlands, told this news organization.
“The evidence now points to unbalanced stress systems as a possible cause of this vulnerability, and now the most important question is, how we can develop preventive interventions,” she added.
The findings were presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
Elevated cortisol, inflammation
The study included 2,779 adults from the Netherlands Study of Depression and Anxiety (NESDA). Two thirds of participants were female.
Participants retrospectively reported childhood trauma, defined as emotional, physical, or sexual abuse or emotional or physical neglect, before the age of 18 years. Severe trauma was defined as multiple types or increased frequency of abuse.
Of the total cohort, 48% reported experiencing some childhood trauma – 21% reported severe trauma, 27% reported mild trauma, and 42% reported no childhood trauma.
Among those with trauma, 89% had a current or remitted anxiety or depressive disorder, and 11% had no psychiatric sequelae. Among participants who reported no trauma, 68% had a current or remitted disorder, and 32% had no psychiatric disorders.
At baseline, researchers assessed markers of major bodily stress systems, including the hypothalamic-pituitary-adrenal (HPA) axis, the immune-inflammatory system, and the autonomic nervous system (ANS). They examined these markers separately and cumulatively.
In one model, investigators found that levels of cortisol and inflammation were significantly elevated in those with severe childhood trauma compared to those with no childhood trauma. The effects were largest for the cumulative markers for HPA-axis, inflammation, and all stress system markers (Cohen’s d = 0.23, 0.12, and 0.25, respectively). There was no association with ANS markers.
The results were partially explained by lifestyle, said Ms. Kuzminskaite, who noted that people with severe childhood trauma tend to have a higher body mass index, smoke more, and have other unhealthy habits that may represent a “coping” mechanism for trauma.
Those who experienced childhood trauma also have higher rates of other disorders, including asthma, diabetes, and cardiovascular disease. Ms. Kuzminskaite noted that people with childhood trauma have at least double the risk of cancer in later life.
When researchers adjusted for lifestyle factors and chronic conditions, the association for cortisol was reduced and that for inflammation disappeared. However, the cumulative inflammatory markers remained significant.
Another model examined lipopolysaccharide-stimulated (LPS) immune-inflammatory markers by childhood trauma severity. This provides a more “dynamic” measure of stress systems than looking only at static circulating levels in the blood, as was done in the first model, said Ms. Kuzminskaite.
“These levels should theoretically be more affected by experiences such as childhood trauma and they are also less sensitive to lifestyle.”
Here, researchers found significant positive associations with childhood trauma, especially severe trauma, after adjusting for lifestyle and health-related covariates (cumulative index d = 0.19).
“Almost all people with childhood trauma, especially severe trauma, had LPS-stimulated cytokines upregulated,” said Ms. Kuzminskaite. “So again, there is this dysregulation of immune system functioning in these subjects.”
And again, the strongest effect was for the cumulative index of all cytokines, she said.
Personalized interventions
Ms. Kuzminskaite noted the importance of learning the impact of early trauma on stress responses. “The goal is to eventually have personalized interventions for people with depression or anxiety related to childhood trauma, or even preventative interventions. If we know, for example, something is going wrong with a patient’s stress systems, we can suggest some therapeutic targets.”
Investigators in Amsterdam are examining the efficacy of mifepristone, which blocks progesterone and is used along with misoprostol for medication abortions and to treat high blood sugar. “The drug is supposed to reset the stress system functioning,” said Ms. Kuzminskaite.
It’s still important to target unhealthy lifestyle habits “that are really impacting the functioning of the stress systems,” she said. Lifestyle interventions could improve the efficacy of treatments for depression, for example, she added.
Luana Marques, PhD, associate professor, department of psychiatry, Harvard Medical School, Boston, said such research is important.
“It reveals the potentially extensive and long-lasting impact of childhood trauma on functioning. The findings underscore the importance of equipping at-risk and trauma-exposed youth with evidence-based skills for managing stress,” she said.
No conflicts of interest were reported.
A version of this article first appeared on Medscape.com.
WASHINGTON –
“We already knew childhood trauma is associated with the later development of depressive and anxiety disorders, but it’s been unclear what makes sufferers of early trauma more likely to develop these psychiatric conditions,” study investigator Erika Kuzminskaite, PhD candidate, department of psychiatry, Amsterdam University Medical Center (UMC), the Netherlands, told this news organization.
“The evidence now points to unbalanced stress systems as a possible cause of this vulnerability, and now the most important question is, how we can develop preventive interventions,” she added.
The findings were presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
Elevated cortisol, inflammation
The study included 2,779 adults from the Netherlands Study of Depression and Anxiety (NESDA). Two thirds of participants were female.
Participants retrospectively reported childhood trauma, defined as emotional, physical, or sexual abuse or emotional or physical neglect, before the age of 18 years. Severe trauma was defined as multiple types or increased frequency of abuse.
Of the total cohort, 48% reported experiencing some childhood trauma – 21% reported severe trauma, 27% reported mild trauma, and 42% reported no childhood trauma.
Among those with trauma, 89% had a current or remitted anxiety or depressive disorder, and 11% had no psychiatric sequelae. Among participants who reported no trauma, 68% had a current or remitted disorder, and 32% had no psychiatric disorders.
At baseline, researchers assessed markers of major bodily stress systems, including the hypothalamic-pituitary-adrenal (HPA) axis, the immune-inflammatory system, and the autonomic nervous system (ANS). They examined these markers separately and cumulatively.
In one model, investigators found that levels of cortisol and inflammation were significantly elevated in those with severe childhood trauma compared to those with no childhood trauma. The effects were largest for the cumulative markers for HPA-axis, inflammation, and all stress system markers (Cohen’s d = 0.23, 0.12, and 0.25, respectively). There was no association with ANS markers.
The results were partially explained by lifestyle, said Ms. Kuzminskaite, who noted that people with severe childhood trauma tend to have a higher body mass index, smoke more, and have other unhealthy habits that may represent a “coping” mechanism for trauma.
Those who experienced childhood trauma also have higher rates of other disorders, including asthma, diabetes, and cardiovascular disease. Ms. Kuzminskaite noted that people with childhood trauma have at least double the risk of cancer in later life.
When researchers adjusted for lifestyle factors and chronic conditions, the association for cortisol was reduced and that for inflammation disappeared. However, the cumulative inflammatory markers remained significant.
Another model examined lipopolysaccharide-stimulated (LPS) immune-inflammatory markers by childhood trauma severity. This provides a more “dynamic” measure of stress systems than looking only at static circulating levels in the blood, as was done in the first model, said Ms. Kuzminskaite.
“These levels should theoretically be more affected by experiences such as childhood trauma and they are also less sensitive to lifestyle.”
Here, researchers found significant positive associations with childhood trauma, especially severe trauma, after adjusting for lifestyle and health-related covariates (cumulative index d = 0.19).
“Almost all people with childhood trauma, especially severe trauma, had LPS-stimulated cytokines upregulated,” said Ms. Kuzminskaite. “So again, there is this dysregulation of immune system functioning in these subjects.”
And again, the strongest effect was for the cumulative index of all cytokines, she said.
Personalized interventions
Ms. Kuzminskaite noted the importance of learning the impact of early trauma on stress responses. “The goal is to eventually have personalized interventions for people with depression or anxiety related to childhood trauma, or even preventative interventions. If we know, for example, something is going wrong with a patient’s stress systems, we can suggest some therapeutic targets.”
Investigators in Amsterdam are examining the efficacy of mifepristone, which blocks progesterone and is used along with misoprostol for medication abortions and to treat high blood sugar. “The drug is supposed to reset the stress system functioning,” said Ms. Kuzminskaite.
It’s still important to target unhealthy lifestyle habits “that are really impacting the functioning of the stress systems,” she said. Lifestyle interventions could improve the efficacy of treatments for depression, for example, she added.
Luana Marques, PhD, associate professor, department of psychiatry, Harvard Medical School, Boston, said such research is important.
“It reveals the potentially extensive and long-lasting impact of childhood trauma on functioning. The findings underscore the importance of equipping at-risk and trauma-exposed youth with evidence-based skills for managing stress,” she said.
No conflicts of interest were reported.
A version of this article first appeared on Medscape.com.
WASHINGTON –
“We already knew childhood trauma is associated with the later development of depressive and anxiety disorders, but it’s been unclear what makes sufferers of early trauma more likely to develop these psychiatric conditions,” study investigator Erika Kuzminskaite, PhD candidate, department of psychiatry, Amsterdam University Medical Center (UMC), the Netherlands, told this news organization.
“The evidence now points to unbalanced stress systems as a possible cause of this vulnerability, and now the most important question is, how we can develop preventive interventions,” she added.
The findings were presented as part of the Anxiety and Depression Association of America Anxiety & Depression conference.
Elevated cortisol, inflammation
The study included 2,779 adults from the Netherlands Study of Depression and Anxiety (NESDA). Two thirds of participants were female.
Participants retrospectively reported childhood trauma, defined as emotional, physical, or sexual abuse or emotional or physical neglect, before the age of 18 years. Severe trauma was defined as multiple types or increased frequency of abuse.
Of the total cohort, 48% reported experiencing some childhood trauma – 21% reported severe trauma, 27% reported mild trauma, and 42% reported no childhood trauma.
Among those with trauma, 89% had a current or remitted anxiety or depressive disorder, and 11% had no psychiatric sequelae. Among participants who reported no trauma, 68% had a current or remitted disorder, and 32% had no psychiatric disorders.
At baseline, researchers assessed markers of major bodily stress systems, including the hypothalamic-pituitary-adrenal (HPA) axis, the immune-inflammatory system, and the autonomic nervous system (ANS). They examined these markers separately and cumulatively.
In one model, investigators found that levels of cortisol and inflammation were significantly elevated in those with severe childhood trauma compared to those with no childhood trauma. The effects were largest for the cumulative markers for HPA-axis, inflammation, and all stress system markers (Cohen’s d = 0.23, 0.12, and 0.25, respectively). There was no association with ANS markers.
The results were partially explained by lifestyle, said Ms. Kuzminskaite, who noted that people with severe childhood trauma tend to have a higher body mass index, smoke more, and have other unhealthy habits that may represent a “coping” mechanism for trauma.
Those who experienced childhood trauma also have higher rates of other disorders, including asthma, diabetes, and cardiovascular disease. Ms. Kuzminskaite noted that people with childhood trauma have at least double the risk of cancer in later life.
When researchers adjusted for lifestyle factors and chronic conditions, the association for cortisol was reduced and that for inflammation disappeared. However, the cumulative inflammatory markers remained significant.
Another model examined lipopolysaccharide-stimulated (LPS) immune-inflammatory markers by childhood trauma severity. This provides a more “dynamic” measure of stress systems than looking only at static circulating levels in the blood, as was done in the first model, said Ms. Kuzminskaite.
“These levels should theoretically be more affected by experiences such as childhood trauma and they are also less sensitive to lifestyle.”
Here, researchers found significant positive associations with childhood trauma, especially severe trauma, after adjusting for lifestyle and health-related covariates (cumulative index d = 0.19).
“Almost all people with childhood trauma, especially severe trauma, had LPS-stimulated cytokines upregulated,” said Ms. Kuzminskaite. “So again, there is this dysregulation of immune system functioning in these subjects.”
And again, the strongest effect was for the cumulative index of all cytokines, she said.
Personalized interventions
Ms. Kuzminskaite noted the importance of learning the impact of early trauma on stress responses. “The goal is to eventually have personalized interventions for people with depression or anxiety related to childhood trauma, or even preventative interventions. If we know, for example, something is going wrong with a patient’s stress systems, we can suggest some therapeutic targets.”
Investigators in Amsterdam are examining the efficacy of mifepristone, which blocks progesterone and is used along with misoprostol for medication abortions and to treat high blood sugar. “The drug is supposed to reset the stress system functioning,” said Ms. Kuzminskaite.
It’s still important to target unhealthy lifestyle habits “that are really impacting the functioning of the stress systems,” she said. Lifestyle interventions could improve the efficacy of treatments for depression, for example, she added.
Luana Marques, PhD, associate professor, department of psychiatry, Harvard Medical School, Boston, said such research is important.
“It reveals the potentially extensive and long-lasting impact of childhood trauma on functioning. The findings underscore the importance of equipping at-risk and trauma-exposed youth with evidence-based skills for managing stress,” she said.
No conflicts of interest were reported.
A version of this article first appeared on Medscape.com.
AT ADAA 2023
Normal CRP during RA flares: An ‘underappreciated, persistent phenotype’
MANCHESTER, England – Even when C-reactive protein (CRP) levels are normal, patients with seropositive rheumatoid arthritis (RA) could still be experiencing significant disease that persists over time, researchers from University College London have found.
Similar levels of joint erosion and disease activity were observed over a 5-year period; researchers compared patients who had high CRP levels (> 5 mg/L)* with patients whose CRP levels were consistently normal (< 5 mg/L) at the time of an ultrasound-proven disease flare.
“Our data suggests that the phenotype of normal CRP represents at least 5% of our cohort,” Bhavika Sethi, MBChB, reported in a virtual poster presentation at the annual meeting of the British Society for Rheumatology.
“They are more likely to require biologic treatment, and this continues on even though they have equivalent DAS28 [disease activity score in 28 joints] and risk of joint damage” to high-CRP patients, she said.
These patients are a significant minority, Dr. Sethi added, and “we need to think about how we provide care for them and allocate resources.”
Diagnostic delay and poor outcomes previously seen
The study is a continuation of a larger project, the corresponding author for the poster, Matthew Hutchinson, MBChB, told this news organization.
A few years ago, Dr. Hutchinson explained, a subset of patients with normal CRP levels during RA flares were identified and were found to be more likely to have experienced diagnostic delay and worse outcomes than did those with high CRP levels.
The aim of the current study was to see whether those findings persisted by longitudinally assessing patient records and seeing what happened 1, 2, and 5 years later. They evaluated 312 patients with seropositive RA, of whom 28 had CRP < 5 mg/L as well as active disease, which was determined on the basis of a DAS28 > 4.5. Of those 28 patients, 16 had persistently low CRP (< 5 mg/L) despite active disease. All patients who were taking tocilizumab were excluded from the study because of its CRP-lowering properties.
“Our project was showing that this group of people exist, trying to characterize them a little better” and that the study serves as a “jumping-off point” for future research, Dr. Hutchinson said.
The study was also conducted to “make people more aware of [patients with normal CRP during flare], because treating clinicians could be falsely reassured by a normal CRP,” he added. “Patients in front of them could actually be undertreated and have worse outcomes if [it is] not picked up,” Dr. Hutchinson suggested.
In comparison with those with high CRP levels, those with normal CRP levels were more likely to be receiving biologic treatment at 5 years (76.6% vs. 44.4%; P = .0323).
At 5 years, DAS28 was similar (P = .9615) among patients with normal CRP levels and those with high CRP levels, at a median of 2.8 and 3.2, respectively. A similar percentage of patients in these two groups also had joint damage (63.3% vs. 71.4%; P = .7384).
Don’t rely only on CRP to diagnose and manage RA flares
“CRP is a generic inflammatory marker in most people,” Dr. Hutchinson said. “In the majority of situations when either there is inflammation or an infection, certainly if it’s systemic infection or inflammation, you will find CRP being elevated on the blood tests.”
For someone presenting with joint pain, high CRP can be a useful indicator that it’s more of an inflammatory process than physical injury, he added. CRP is also frequently used to calculate DAS28 to monitor disease activity.
“This study highlights that CRP may be normal during flares in some people with RA,” Jeffrey A. Sparks, MD, told this news organization.
“These patients may still require advanced therapies and can accrue damage,” the rheumatologist from Brigham and Women’s Hospital and Harvard University, Boston, added.
“Clinicians should not only rely on CRP to diagnose and manage RA flares,” said Dr. Sparks, who was not involved in the study.
The study was independently supported. Dr. Hutchinson and Dr. Sethi report no relevant financial relationships. Dr. Sparks is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the R. Bruce and Joan M. Mickey Research Scholar Fund, and the Llura Gund Award for Rheumatoid Arthritis Research and Care; he has received research support from Bristol-Myers Squibb and has performed consultancy for AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer.
*Correction, 5/9/2023: This article has been updated to correct the units for C-reactive protein from mg/dL to mg/L.
A version of this article first appeared on Medscape.com.
MANCHESTER, England – Even when C-reactive protein (CRP) levels are normal, patients with seropositive rheumatoid arthritis (RA) could still be experiencing significant disease that persists over time, researchers from University College London have found.
Similar levels of joint erosion and disease activity were observed over a 5-year period; researchers compared patients who had high CRP levels (> 5 mg/L)* with patients whose CRP levels were consistently normal (< 5 mg/L) at the time of an ultrasound-proven disease flare.
“Our data suggests that the phenotype of normal CRP represents at least 5% of our cohort,” Bhavika Sethi, MBChB, reported in a virtual poster presentation at the annual meeting of the British Society for Rheumatology.
“They are more likely to require biologic treatment, and this continues on even though they have equivalent DAS28 [disease activity score in 28 joints] and risk of joint damage” to high-CRP patients, she said.
These patients are a significant minority, Dr. Sethi added, and “we need to think about how we provide care for them and allocate resources.”
Diagnostic delay and poor outcomes previously seen
The study is a continuation of a larger project, the corresponding author for the poster, Matthew Hutchinson, MBChB, told this news organization.
A few years ago, Dr. Hutchinson explained, a subset of patients with normal CRP levels during RA flares were identified and were found to be more likely to have experienced diagnostic delay and worse outcomes than did those with high CRP levels.
The aim of the current study was to see whether those findings persisted by longitudinally assessing patient records and seeing what happened 1, 2, and 5 years later. They evaluated 312 patients with seropositive RA, of whom 28 had CRP < 5 mg/L as well as active disease, which was determined on the basis of a DAS28 > 4.5. Of those 28 patients, 16 had persistently low CRP (< 5 mg/L) despite active disease. All patients who were taking tocilizumab were excluded from the study because of its CRP-lowering properties.
“Our project was showing that this group of people exist, trying to characterize them a little better” and that the study serves as a “jumping-off point” for future research, Dr. Hutchinson said.
The study was also conducted to “make people more aware of [patients with normal CRP during flare], because treating clinicians could be falsely reassured by a normal CRP,” he added. “Patients in front of them could actually be undertreated and have worse outcomes if [it is] not picked up,” Dr. Hutchinson suggested.
In comparison with those with high CRP levels, those with normal CRP levels were more likely to be receiving biologic treatment at 5 years (76.6% vs. 44.4%; P = .0323).
At 5 years, DAS28 was similar (P = .9615) among patients with normal CRP levels and those with high CRP levels, at a median of 2.8 and 3.2, respectively. A similar percentage of patients in these two groups also had joint damage (63.3% vs. 71.4%; P = .7384).
Don’t rely only on CRP to diagnose and manage RA flares
“CRP is a generic inflammatory marker in most people,” Dr. Hutchinson said. “In the majority of situations when either there is inflammation or an infection, certainly if it’s systemic infection or inflammation, you will find CRP being elevated on the blood tests.”
For someone presenting with joint pain, high CRP can be a useful indicator that it’s more of an inflammatory process than physical injury, he added. CRP is also frequently used to calculate DAS28 to monitor disease activity.
“This study highlights that CRP may be normal during flares in some people with RA,” Jeffrey A. Sparks, MD, told this news organization.
“These patients may still require advanced therapies and can accrue damage,” the rheumatologist from Brigham and Women’s Hospital and Harvard University, Boston, added.
“Clinicians should not only rely on CRP to diagnose and manage RA flares,” said Dr. Sparks, who was not involved in the study.
The study was independently supported. Dr. Hutchinson and Dr. Sethi report no relevant financial relationships. Dr. Sparks is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the R. Bruce and Joan M. Mickey Research Scholar Fund, and the Llura Gund Award for Rheumatoid Arthritis Research and Care; he has received research support from Bristol-Myers Squibb and has performed consultancy for AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer.
*Correction, 5/9/2023: This article has been updated to correct the units for C-reactive protein from mg/dL to mg/L.
A version of this article first appeared on Medscape.com.
MANCHESTER, England – Even when C-reactive protein (CRP) levels are normal, patients with seropositive rheumatoid arthritis (RA) could still be experiencing significant disease that persists over time, researchers from University College London have found.
Similar levels of joint erosion and disease activity were observed over a 5-year period; researchers compared patients who had high CRP levels (> 5 mg/L)* with patients whose CRP levels were consistently normal (< 5 mg/L) at the time of an ultrasound-proven disease flare.
“Our data suggests that the phenotype of normal CRP represents at least 5% of our cohort,” Bhavika Sethi, MBChB, reported in a virtual poster presentation at the annual meeting of the British Society for Rheumatology.
“They are more likely to require biologic treatment, and this continues on even though they have equivalent DAS28 [disease activity score in 28 joints] and risk of joint damage” to high-CRP patients, she said.
These patients are a significant minority, Dr. Sethi added, and “we need to think about how we provide care for them and allocate resources.”
Diagnostic delay and poor outcomes previously seen
The study is a continuation of a larger project, the corresponding author for the poster, Matthew Hutchinson, MBChB, told this news organization.
A few years ago, Dr. Hutchinson explained, a subset of patients with normal CRP levels during RA flares were identified and were found to be more likely to have experienced diagnostic delay and worse outcomes than did those with high CRP levels.
The aim of the current study was to see whether those findings persisted by longitudinally assessing patient records and seeing what happened 1, 2, and 5 years later. They evaluated 312 patients with seropositive RA, of whom 28 had CRP < 5 mg/L as well as active disease, which was determined on the basis of a DAS28 > 4.5. Of those 28 patients, 16 had persistently low CRP (< 5 mg/L) despite active disease. All patients who were taking tocilizumab were excluded from the study because of its CRP-lowering properties.
“Our project was showing that this group of people exist, trying to characterize them a little better” and that the study serves as a “jumping-off point” for future research, Dr. Hutchinson said.
The study was also conducted to “make people more aware of [patients with normal CRP during flare], because treating clinicians could be falsely reassured by a normal CRP,” he added. “Patients in front of them could actually be undertreated and have worse outcomes if [it is] not picked up,” Dr. Hutchinson suggested.
In comparison with those with high CRP levels, those with normal CRP levels were more likely to be receiving biologic treatment at 5 years (76.6% vs. 44.4%; P = .0323).
At 5 years, DAS28 was similar (P = .9615) among patients with normal CRP levels and those with high CRP levels, at a median of 2.8 and 3.2, respectively. A similar percentage of patients in these two groups also had joint damage (63.3% vs. 71.4%; P = .7384).
Don’t rely only on CRP to diagnose and manage RA flares
“CRP is a generic inflammatory marker in most people,” Dr. Hutchinson said. “In the majority of situations when either there is inflammation or an infection, certainly if it’s systemic infection or inflammation, you will find CRP being elevated on the blood tests.”
For someone presenting with joint pain, high CRP can be a useful indicator that it’s more of an inflammatory process than physical injury, he added. CRP is also frequently used to calculate DAS28 to monitor disease activity.
“This study highlights that CRP may be normal during flares in some people with RA,” Jeffrey A. Sparks, MD, told this news organization.
“These patients may still require advanced therapies and can accrue damage,” the rheumatologist from Brigham and Women’s Hospital and Harvard University, Boston, added.
“Clinicians should not only rely on CRP to diagnose and manage RA flares,” said Dr. Sparks, who was not involved in the study.
The study was independently supported. Dr. Hutchinson and Dr. Sethi report no relevant financial relationships. Dr. Sparks is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the R. Bruce and Joan M. Mickey Research Scholar Fund, and the Llura Gund Award for Rheumatoid Arthritis Research and Care; he has received research support from Bristol-Myers Squibb and has performed consultancy for AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer.
*Correction, 5/9/2023: This article has been updated to correct the units for C-reactive protein from mg/dL to mg/L.
A version of this article first appeared on Medscape.com.
AT BSR 2023