Federal Practitioner

The American College of Cardiology (ACC), the American Heart Association (AHA), the American College of Chest Physicians (ACCP), and the Heart Rhythm Society (HRS) have issued an updated guideline for preventing and optimally managing atrial fibrillation (AF).

The 2023 ACC/AHA/ACCP/HRS Guideline for Diagnosis and Management of Atrial Fibrillation was published online in the Journal of the American College of Cardiology and Circulation.

“The new guideline has important changes,” including a new way to classify AF, Jose Joglar, MD, professor of cardiac electrophysiology at UT Southwestern Medical Center in Dallas, Texas, and chair of the writing committee, said in an interview.

The previous classification was largely based only on arrhythmia duration and tended to emphasize specific therapeutic interventions rather than a more holistic and multidisciplinary management approach, Dr. Joglar explained.

The new proposed classification, using four stages, recognizes AF as a disease continuum that requires a variety of strategies at different stages, from prevention, lifestyle and risk factor modification, screening, and therapy.

Stage 1: At risk for AF due to the presence of risk factors

Stage 2: Pre-AF, with evidence of structural or electrical findings predisposing to AF

Stage 3: AF, including paroxysmal (3A), persistent (3B), long-standing persistent (3C), successful AF ablation (3D)

Stage 4: Permanent AF

The updated guideline recognizes lifestyle and risk factor modification as a “pillar” of AF management and offers “more prescriptive” recommendations, including management of obesity, weight loss, physical activity, smoking cessation, alcohol moderation, hypertension, and other comorbidities.

“We should not only be telling patients they need to be healthy, which doesn’t mean much to a patient, we need to tell them precisely what they need to do. For example, how much exercise to do or how much weight to lose to have a benefit,” Dr. Joglar said in an interview.

The good news for many people, he noted, is that coffee, which has had a “bad reputation,” is okay, as the latest data show it doesn’t seem to exacerbate AF.

The new guideline continues to endorse use of the CHA2DS2-VASc score as the predictor of choice to determine the risk of stroke, but it also allows for flexibility to use other calculators when uncertainty exists or when other risk factors, such as kidney disease, need to be included.

With the emergence of “new and consistent” evidence, the guideline also emphasizes the importance of early and continued management of patients with AF with a focus on maintaining sinus rhythm and minimizing AF burden.

Catheter ablation of AF is given a class 1 indication as first-line therapy in selected patients, including those with heart failure with reduced ejection fraction.

That’s based on recent randomized studies that have shown catheter ablation to be “superior to pharmacological therapy” for rhythm control in appropriately selected patients, Dr. Joglar told this news organization.

“There’s no need to try pharmacological therapies after a discussion between the patient and doctor and they decide that they want to proceed with the most effective intervention,” he added.

The new guideline also upgrades the class of recommendation for left atrial appendage occlusion devices to 2a, compared with the 2019 AF Focused Update, for use of these devices in patients with long-term contraindications to anticoagulation.

It also provides updated recommendations for AF detected via implantable devices and wearables as well as recommendations for patients with AF identified during medical illness or surgery.

Development of the guideline had no commercial funding. Disclosures for the writing group are available with the original articles.

A version of this article appeared on Medscape.com.

The American College of Cardiology (ACC), the American Heart Association (AHA), the American College of Chest Physicians (ACCP), and the Heart Rhythm Society (HRS) have issued an updated guideline for preventing and optimally managing atrial fibrillation (AF).

The 2023 ACC/AHA/ACCP/HRS Guideline for Diagnosis and Management of Atrial Fibrillation was published online in the Journal of the American College of Cardiology and Circulation.

“The new guideline has important changes,” including a new way to classify AF, Jose Joglar, MD, professor of cardiac electrophysiology at UT Southwestern Medical Center in Dallas, Texas, and chair of the writing committee, said in an interview.

The previous classification was largely based only on arrhythmia duration and tended to emphasize specific therapeutic interventions rather than a more holistic and multidisciplinary management approach, Dr. Joglar explained.

The new proposed classification, using four stages, recognizes AF as a disease continuum that requires a variety of strategies at different stages, from prevention, lifestyle and risk factor modification, screening, and therapy.

Stage 1: At risk for AF due to the presence of risk factors

Stage 2: Pre-AF, with evidence of structural or electrical findings predisposing to AF

Stage 3: AF, including paroxysmal (3A), persistent (3B), long-standing persistent (3C), successful AF ablation (3D)

Stage 4: Permanent AF

The updated guideline recognizes lifestyle and risk factor modification as a “pillar” of AF management and offers “more prescriptive” recommendations, including management of obesity, weight loss, physical activity, smoking cessation, alcohol moderation, hypertension, and other comorbidities.

“We should not only be telling patients they need to be healthy, which doesn’t mean much to a patient, we need to tell them precisely what they need to do. For example, how much exercise to do or how much weight to lose to have a benefit,” Dr. Joglar said in an interview.

The good news for many people, he noted, is that coffee, which has had a “bad reputation,” is okay, as the latest data show it doesn’t seem to exacerbate AF.

The new guideline continues to endorse use of the CHA2DS2-VASc score as the predictor of choice to determine the risk of stroke, but it also allows for flexibility to use other calculators when uncertainty exists or when other risk factors, such as kidney disease, need to be included.

With the emergence of “new and consistent” evidence, the guideline also emphasizes the importance of early and continued management of patients with AF with a focus on maintaining sinus rhythm and minimizing AF burden.

Catheter ablation of AF is given a class 1 indication as first-line therapy in selected patients, including those with heart failure with reduced ejection fraction.

That’s based on recent randomized studies that have shown catheter ablation to be “superior to pharmacological therapy” for rhythm control in appropriately selected patients, Dr. Joglar told this news organization.

“There’s no need to try pharmacological therapies after a discussion between the patient and doctor and they decide that they want to proceed with the most effective intervention,” he added.

The new guideline also upgrades the class of recommendation for left atrial appendage occlusion devices to 2a, compared with the 2019 AF Focused Update, for use of these devices in patients with long-term contraindications to anticoagulation.

It also provides updated recommendations for AF detected via implantable devices and wearables as well as recommendations for patients with AF identified during medical illness or surgery.

Development of the guideline had no commercial funding. Disclosures for the writing group are available with the original articles.

A version of this article appeared on Medscape.com.

The American College of Cardiology (ACC), the American Heart Association (AHA), the American College of Chest Physicians (ACCP), and the Heart Rhythm Society (HRS) have issued an updated guideline for preventing and optimally managing atrial fibrillation (AF).

The 2023 ACC/AHA/ACCP/HRS Guideline for Diagnosis and Management of Atrial Fibrillation was published online in the Journal of the American College of Cardiology and Circulation.

“The new guideline has important changes,” including a new way to classify AF, Jose Joglar, MD, professor of cardiac electrophysiology at UT Southwestern Medical Center in Dallas, Texas, and chair of the writing committee, said in an interview.

The previous classification was largely based only on arrhythmia duration and tended to emphasize specific therapeutic interventions rather than a more holistic and multidisciplinary management approach, Dr. Joglar explained.

The new proposed classification, using four stages, recognizes AF as a disease continuum that requires a variety of strategies at different stages, from prevention, lifestyle and risk factor modification, screening, and therapy.

Stage 1: At risk for AF due to the presence of risk factors

Stage 2: Pre-AF, with evidence of structural or electrical findings predisposing to AF

Stage 3: AF, including paroxysmal (3A), persistent (3B), long-standing persistent (3C), successful AF ablation (3D)

Stage 4: Permanent AF

The updated guideline recognizes lifestyle and risk factor modification as a “pillar” of AF management and offers “more prescriptive” recommendations, including management of obesity, weight loss, physical activity, smoking cessation, alcohol moderation, hypertension, and other comorbidities.

“We should not only be telling patients they need to be healthy, which doesn’t mean much to a patient, we need to tell them precisely what they need to do. For example, how much exercise to do or how much weight to lose to have a benefit,” Dr. Joglar said in an interview.

The good news for many people, he noted, is that coffee, which has had a “bad reputation,” is okay, as the latest data show it doesn’t seem to exacerbate AF.

The new guideline continues to endorse use of the CHA2DS2-VASc score as the predictor of choice to determine the risk of stroke, but it also allows for flexibility to use other calculators when uncertainty exists or when other risk factors, such as kidney disease, need to be included.

With the emergence of “new and consistent” evidence, the guideline also emphasizes the importance of early and continued management of patients with AF with a focus on maintaining sinus rhythm and minimizing AF burden.

Catheter ablation of AF is given a class 1 indication as first-line therapy in selected patients, including those with heart failure with reduced ejection fraction.

That’s based on recent randomized studies that have shown catheter ablation to be “superior to pharmacological therapy” for rhythm control in appropriately selected patients, Dr. Joglar told this news organization.

“There’s no need to try pharmacological therapies after a discussion between the patient and doctor and they decide that they want to proceed with the most effective intervention,” he added.

The new guideline also upgrades the class of recommendation for left atrial appendage occlusion devices to 2a, compared with the 2019 AF Focused Update, for use of these devices in patients with long-term contraindications to anticoagulation.

It also provides updated recommendations for AF detected via implantable devices and wearables as well as recommendations for patients with AF identified during medical illness or surgery.

Development of the guideline had no commercial funding. Disclosures for the writing group are available with the original articles.

A version of this article appeared on Medscape.com.

One of the biggest challenges facing clinicians who treat long COVID is a lack of consensus when it comes to recognizing and diagnosing the condition. But a new study suggests testing for certain biomarkers may identify long COVID with accuracy approaching 80%.

Effective diagnostic testing would be a game-changer in the long COVID fight, for it’s not just the fatigue, brain fog, heart palpitations, and other persistent symptoms that affect patients. Two out of three people with long COVID also suffer mental health challenges like depression and anxiety. Some patients say their symptoms are not taken seriously by their doctors. And as many as 12% of long COVID patients are unemployed because of the severity of their illness and their employers may be skeptical of their condition.

Quick, accurate diagnosis would eliminate all that. Now a new preprint study suggests that the elevation of certain immune system proteins are a commonality in long COVID patients and identifying them may be an accurate way to diagnose the condition.

Researchers at Cardiff (Wales) University, tracked 166 patients, 79 of whom had been diagnosed with long COVID and 87 who had not. All participants had recovered from a severe bout of acute COVID-19.

In an analysis of the blood plasma of the study participants, researchers found elevated levels of certain components. Four proteins in particular – Ba, iC3b, C5a, and TCC – predicted the presence of long COVID with 78.5% accuracy.

“I was gobsmacked by the results. We’re seeing a massive dysregulation in those four biomarkers,” says study author Wioleta Zelek, PhD, a research fellow at Cardiff University. “It’s a combination that we showed was predictive of long COVID.” 

The study revealed that long COVID was associated with inflammation of the immune system causing these complement proteins to remain dysregulated. Proteins like C3, C4, and C5 are important parts of the immune system because they recruit phagocytes, cells that attack and engulf bacteria and viruses at the site of infection to destroy pathogens like SARS-coV-2. 

In the case of long COVID, these proteins remain chronically elevated. While the symptoms of long COVID have seemed largely unrelated to one another, researchers point to elevated inflammation as a connecting factor that causes various systems in the body to go haywire.

“Anything that could help to better diagnose patients with long COVID is research we’re greatly appreciative of within the clinical community,” said Nisha Viswanathan, MD, director of the University of California, Los Angeles, Long COVID program at UCLA Health. 

Testing for biomarkers highlighted in the study, as well as others like serotonin and cortisol, may help doctors separate patients who have long COVID from patients who have similar symptoms caused by other conditions, said Dr. Viswanathan. For example, a recent study published in the journal Cell found lower serotonin levels in long COVID patients, compared with patients who were diagnosed with acute COVID-19 but recovered from the condition.

Dr. Viswanathan cautions that the biomarker test does not answer all the questions about diagnosing long COVID. For example, Dr. Viswanathan said scientists don’t know whether complement dysregulation is caused by long COVID and not another underlying medical issue that patients had prior to infection, because “we don’t know where patients’ levels were prior to developing long COVID.” For example, those with autoimmune issues are more likely to develop long COVID, which means their levels could have been elevated prior to a COVID infection.

It is increasingly likely, said Dr. Viswanathan, that long COVID is an umbrella term for a host of conditions that could be caused by different impacts of the virus. Other research has pointed to the different phenotypes of long COVID. For example, some are focused on cardiopulmonary issues and others on fatigue and gastrointestinal problems. 

“It looks like these different phenotypes have a different mechanism for disease,” she said. This means that it’s less likely to be a one-size-fits-all condition and the next step in the research should be identifying which biomarker is aligned with which phenotype of the disease. 

Better diagnostics will open the door to better treatments, Dr. Zelek said. The more doctors understand about the mechanism causing immune dysregulation in long COVID patients, the more they can treat it with existing medications. Dr. Zelek’s lab has been studying certain medications like pegcetacoplan (C3 blocker), danicopan (anti-factor D), and iptacopan (anti-factor B) that can be used to break the body’s cycle of inflammation and reduce symptoms experienced in those with long COVID. 

These drugs are approved by the U.S. Food and Drug Administration for the treatment of a rare blood disease called paroxysmal nocturnal hemoglobinuria. The C5 inhibitor zilucoplan has also been used in patients hospitalized with COVID-19 and researchers have found that the drug lowered serum C5 and interleukin-8 concentration in the blood, seeming to reduce certain aspects of the immune system’s inflammatory response to the virus. 

The Cardiff University research is one of the most detailed studies to highlight long COVID biomarkers to date, said infectious disease specialist Grace McComsey, MD, who leads the long COVID RECOVER study at University Hospitals Health System in Cleveland, Ohio. The research needs to be duplicated in a larger study population that might include the other biomarkers like serotonin and cortisol to see if they’re related, she said. 

Researchers are learning more everyday about the various biomarkers that may be linked to long COVID, she added. This Cardiff study showed that a huge percentage of those patients had elevated levels of certain complements. The next step, said Dr. McComsey, “is to put all these puzzle pieces together” so that clinicians have a common diagnostic tool or tools that provide patients with some peace of mind in starting their road to recovery.

A version of this article first appeared on Medscape.com.

One of the biggest challenges facing clinicians who treat long COVID is a lack of consensus when it comes to recognizing and diagnosing the condition. But a new study suggests testing for certain biomarkers may identify long COVID with accuracy approaching 80%.

Effective diagnostic testing would be a game-changer in the long COVID fight, for it’s not just the fatigue, brain fog, heart palpitations, and other persistent symptoms that affect patients. Two out of three people with long COVID also suffer mental health challenges like depression and anxiety. Some patients say their symptoms are not taken seriously by their doctors. And as many as 12% of long COVID patients are unemployed because of the severity of their illness and their employers may be skeptical of their condition.

Quick, accurate diagnosis would eliminate all that. Now a new preprint study suggests that the elevation of certain immune system proteins are a commonality in long COVID patients and identifying them may be an accurate way to diagnose the condition.

Researchers at Cardiff (Wales) University, tracked 166 patients, 79 of whom had been diagnosed with long COVID and 87 who had not. All participants had recovered from a severe bout of acute COVID-19.

In an analysis of the blood plasma of the study participants, researchers found elevated levels of certain components. Four proteins in particular – Ba, iC3b, C5a, and TCC – predicted the presence of long COVID with 78.5% accuracy.

“I was gobsmacked by the results. We’re seeing a massive dysregulation in those four biomarkers,” says study author Wioleta Zelek, PhD, a research fellow at Cardiff University. “It’s a combination that we showed was predictive of long COVID.” 

The study revealed that long COVID was associated with inflammation of the immune system causing these complement proteins to remain dysregulated. Proteins like C3, C4, and C5 are important parts of the immune system because they recruit phagocytes, cells that attack and engulf bacteria and viruses at the site of infection to destroy pathogens like SARS-coV-2. 

In the case of long COVID, these proteins remain chronically elevated. While the symptoms of long COVID have seemed largely unrelated to one another, researchers point to elevated inflammation as a connecting factor that causes various systems in the body to go haywire.

“Anything that could help to better diagnose patients with long COVID is research we’re greatly appreciative of within the clinical community,” said Nisha Viswanathan, MD, director of the University of California, Los Angeles, Long COVID program at UCLA Health. 

Testing for biomarkers highlighted in the study, as well as others like serotonin and cortisol, may help doctors separate patients who have long COVID from patients who have similar symptoms caused by other conditions, said Dr. Viswanathan. For example, a recent study published in the journal Cell found lower serotonin levels in long COVID patients, compared with patients who were diagnosed with acute COVID-19 but recovered from the condition.

Dr. Viswanathan cautions that the biomarker test does not answer all the questions about diagnosing long COVID. For example, Dr. Viswanathan said scientists don’t know whether complement dysregulation is caused by long COVID and not another underlying medical issue that patients had prior to infection, because “we don’t know where patients’ levels were prior to developing long COVID.” For example, those with autoimmune issues are more likely to develop long COVID, which means their levels could have been elevated prior to a COVID infection.

It is increasingly likely, said Dr. Viswanathan, that long COVID is an umbrella term for a host of conditions that could be caused by different impacts of the virus. Other research has pointed to the different phenotypes of long COVID. For example, some are focused on cardiopulmonary issues and others on fatigue and gastrointestinal problems. 

“It looks like these different phenotypes have a different mechanism for disease,” she said. This means that it’s less likely to be a one-size-fits-all condition and the next step in the research should be identifying which biomarker is aligned with which phenotype of the disease. 

Better diagnostics will open the door to better treatments, Dr. Zelek said. The more doctors understand about the mechanism causing immune dysregulation in long COVID patients, the more they can treat it with existing medications. Dr. Zelek’s lab has been studying certain medications like pegcetacoplan (C3 blocker), danicopan (anti-factor D), and iptacopan (anti-factor B) that can be used to break the body’s cycle of inflammation and reduce symptoms experienced in those with long COVID. 

These drugs are approved by the U.S. Food and Drug Administration for the treatment of a rare blood disease called paroxysmal nocturnal hemoglobinuria. The C5 inhibitor zilucoplan has also been used in patients hospitalized with COVID-19 and researchers have found that the drug lowered serum C5 and interleukin-8 concentration in the blood, seeming to reduce certain aspects of the immune system’s inflammatory response to the virus. 

The Cardiff University research is one of the most detailed studies to highlight long COVID biomarkers to date, said infectious disease specialist Grace McComsey, MD, who leads the long COVID RECOVER study at University Hospitals Health System in Cleveland, Ohio. The research needs to be duplicated in a larger study population that might include the other biomarkers like serotonin and cortisol to see if they’re related, she said. 

Researchers are learning more everyday about the various biomarkers that may be linked to long COVID, she added. This Cardiff study showed that a huge percentage of those patients had elevated levels of certain complements. The next step, said Dr. McComsey, “is to put all these puzzle pieces together” so that clinicians have a common diagnostic tool or tools that provide patients with some peace of mind in starting their road to recovery.

A version of this article first appeared on Medscape.com.

One of the biggest challenges facing clinicians who treat long COVID is a lack of consensus when it comes to recognizing and diagnosing the condition. But a new study suggests testing for certain biomarkers may identify long COVID with accuracy approaching 80%.

Effective diagnostic testing would be a game-changer in the long COVID fight, for it’s not just the fatigue, brain fog, heart palpitations, and other persistent symptoms that affect patients. Two out of three people with long COVID also suffer mental health challenges like depression and anxiety. Some patients say their symptoms are not taken seriously by their doctors. And as many as 12% of long COVID patients are unemployed because of the severity of their illness and their employers may be skeptical of their condition.

Quick, accurate diagnosis would eliminate all that. Now a new preprint study suggests that the elevation of certain immune system proteins are a commonality in long COVID patients and identifying them may be an accurate way to diagnose the condition.

Researchers at Cardiff (Wales) University, tracked 166 patients, 79 of whom had been diagnosed with long COVID and 87 who had not. All participants had recovered from a severe bout of acute COVID-19.

In an analysis of the blood plasma of the study participants, researchers found elevated levels of certain components. Four proteins in particular – Ba, iC3b, C5a, and TCC – predicted the presence of long COVID with 78.5% accuracy.

“I was gobsmacked by the results. We’re seeing a massive dysregulation in those four biomarkers,” says study author Wioleta Zelek, PhD, a research fellow at Cardiff University. “It’s a combination that we showed was predictive of long COVID.” 

The study revealed that long COVID was associated with inflammation of the immune system causing these complement proteins to remain dysregulated. Proteins like C3, C4, and C5 are important parts of the immune system because they recruit phagocytes, cells that attack and engulf bacteria and viruses at the site of infection to destroy pathogens like SARS-coV-2. 

In the case of long COVID, these proteins remain chronically elevated. While the symptoms of long COVID have seemed largely unrelated to one another, researchers point to elevated inflammation as a connecting factor that causes various systems in the body to go haywire.

“Anything that could help to better diagnose patients with long COVID is research we’re greatly appreciative of within the clinical community,” said Nisha Viswanathan, MD, director of the University of California, Los Angeles, Long COVID program at UCLA Health. 

Testing for biomarkers highlighted in the study, as well as others like serotonin and cortisol, may help doctors separate patients who have long COVID from patients who have similar symptoms caused by other conditions, said Dr. Viswanathan. For example, a recent study published in the journal Cell found lower serotonin levels in long COVID patients, compared with patients who were diagnosed with acute COVID-19 but recovered from the condition.

Dr. Viswanathan cautions that the biomarker test does not answer all the questions about diagnosing long COVID. For example, Dr. Viswanathan said scientists don’t know whether complement dysregulation is caused by long COVID and not another underlying medical issue that patients had prior to infection, because “we don’t know where patients’ levels were prior to developing long COVID.” For example, those with autoimmune issues are more likely to develop long COVID, which means their levels could have been elevated prior to a COVID infection.

It is increasingly likely, said Dr. Viswanathan, that long COVID is an umbrella term for a host of conditions that could be caused by different impacts of the virus. Other research has pointed to the different phenotypes of long COVID. For example, some are focused on cardiopulmonary issues and others on fatigue and gastrointestinal problems. 

“It looks like these different phenotypes have a different mechanism for disease,” she said. This means that it’s less likely to be a one-size-fits-all condition and the next step in the research should be identifying which biomarker is aligned with which phenotype of the disease. 

Better diagnostics will open the door to better treatments, Dr. Zelek said. The more doctors understand about the mechanism causing immune dysregulation in long COVID patients, the more they can treat it with existing medications. Dr. Zelek’s lab has been studying certain medications like pegcetacoplan (C3 blocker), danicopan (anti-factor D), and iptacopan (anti-factor B) that can be used to break the body’s cycle of inflammation and reduce symptoms experienced in those with long COVID. 

These drugs are approved by the U.S. Food and Drug Administration for the treatment of a rare blood disease called paroxysmal nocturnal hemoglobinuria. The C5 inhibitor zilucoplan has also been used in patients hospitalized with COVID-19 and researchers have found that the drug lowered serum C5 and interleukin-8 concentration in the blood, seeming to reduce certain aspects of the immune system’s inflammatory response to the virus. 

The Cardiff University research is one of the most detailed studies to highlight long COVID biomarkers to date, said infectious disease specialist Grace McComsey, MD, who leads the long COVID RECOVER study at University Hospitals Health System in Cleveland, Ohio. The research needs to be duplicated in a larger study population that might include the other biomarkers like serotonin and cortisol to see if they’re related, she said. 

Researchers are learning more everyday about the various biomarkers that may be linked to long COVID, she added. This Cardiff study showed that a huge percentage of those patients had elevated levels of certain complements. The next step, said Dr. McComsey, “is to put all these puzzle pieces together” so that clinicians have a common diagnostic tool or tools that provide patients with some peace of mind in starting their road to recovery.

A version of this article first appeared on Medscape.com.

TOPLINE:

Biopsies that rely on MRI to detect prostate cancer are worth the cost, according to research published online  in JAMA Network Open.

METHODOLOGY:

• Investigators ran a simulation of a hypothetical group of 65-year-old men who were at risk for the cancer, as indicated by their prostate-specific antigen (PSA) levels.
• The costs and benefits of periodic ultrasound biopsies were modeled in comparison with those of an annual MRI plus MRI-guided biopsies using epidemiologic and clinical data.
• The investigators compared the cost-effectiveness of each biopsy approach over a decade, as measured by the cost of procedures divided by the projected gain in life-years.
• Cost-effectiveness was defined as less than $100,000 for each life-year gain using an MRI in comparison with ultrasound.
• They stratified the cost-effectiveness of the MRI approach by severity of PSA level: less than 2.5 ng/mL, 2.5-4.0 ng/mL, 4.1-10.0 ng/mL, and greater than 10.0 ng/mL.

TAKEAWAY:

• For three of the four PSA levels (2.5-4.0 ng/mL, 4.1-10.0 ng/mL, and greater than 10.0 ng/mL) the combination of MRI plus MRI-guided biopsy was cost effective.
• The MRI-based approach cost $6,000 more than ultrasound for each life-year gained at the highest PSA level of greater than 10.0 ng/mL, which was significantly below the $100,000 threshold.
• At the lowest PSA level of less than 2.5 ng/mL, the difference between MRI and ultrasound was $187,000, which was above the threshold.

IN PRACTICE:

The researchers wrote that there is “a growing consensus that the use of MRI and potential MRI-guided biopsy is cost effective.”

SOURCE:

Ali Jalali, PhD, a health economist at Weill Cornell Medicine, New York, is the senior author of the study. Simulation data come from the National Vital Statistics Report of the Centers for Disease Control and Prevention and the Medicare fee schedule.

LIMITATIONS:

The study is a hypothetical simulation of what could happen under different conditions, not an analysis of data developed over time in clinical practice. It also assumes that PSA levels remain constant over time.

DISCLOSURES:

One author receives grants from Siemens Healthineers for MRI technology development, and another author consults for Promaxo, which develops MRI tools.

A version of this article first appeared on Medscape.com.

TOPLINE:

Biopsies that rely on MRI to detect prostate cancer are worth the cost, according to research published online  in JAMA Network Open.

METHODOLOGY:

• Investigators ran a simulation of a hypothetical group of 65-year-old men who were at risk for the cancer, as indicated by their prostate-specific antigen (PSA) levels.
• The costs and benefits of periodic ultrasound biopsies were modeled in comparison with those of an annual MRI plus MRI-guided biopsies using epidemiologic and clinical data.
• The investigators compared the cost-effectiveness of each biopsy approach over a decade, as measured by the cost of procedures divided by the projected gain in life-years.
• Cost-effectiveness was defined as less than $100,000 for each life-year gain using an MRI in comparison with ultrasound.
• They stratified the cost-effectiveness of the MRI approach by severity of PSA level: less than 2.5 ng/mL, 2.5-4.0 ng/mL, 4.1-10.0 ng/mL, and greater than 10.0 ng/mL.

TAKEAWAY:

• For three of the four PSA levels (2.5-4.0 ng/mL, 4.1-10.0 ng/mL, and greater than 10.0 ng/mL) the combination of MRI plus MRI-guided biopsy was cost effective.
• The MRI-based approach cost $6,000 more than ultrasound for each life-year gained at the highest PSA level of greater than 10.0 ng/mL, which was significantly below the $100,000 threshold.
• At the lowest PSA level of less than 2.5 ng/mL, the difference between MRI and ultrasound was $187,000, which was above the threshold.

IN PRACTICE:

The researchers wrote that there is “a growing consensus that the use of MRI and potential MRI-guided biopsy is cost effective.”

SOURCE:

Ali Jalali, PhD, a health economist at Weill Cornell Medicine, New York, is the senior author of the study. Simulation data come from the National Vital Statistics Report of the Centers for Disease Control and Prevention and the Medicare fee schedule.

LIMITATIONS:

The study is a hypothetical simulation of what could happen under different conditions, not an analysis of data developed over time in clinical practice. It also assumes that PSA levels remain constant over time.

DISCLOSURES:

One author receives grants from Siemens Healthineers for MRI technology development, and another author consults for Promaxo, which develops MRI tools.

A version of this article first appeared on Medscape.com.

TOPLINE:

Biopsies that rely on MRI to detect prostate cancer are worth the cost, according to research published online  in JAMA Network Open.

METHODOLOGY:

• Investigators ran a simulation of a hypothetical group of 65-year-old men who were at risk for the cancer, as indicated by their prostate-specific antigen (PSA) levels.
• The costs and benefits of periodic ultrasound biopsies were modeled in comparison with those of an annual MRI plus MRI-guided biopsies using epidemiologic and clinical data.
• The investigators compared the cost-effectiveness of each biopsy approach over a decade, as measured by the cost of procedures divided by the projected gain in life-years.
• Cost-effectiveness was defined as less than $100,000 for each life-year gain using an MRI in comparison with ultrasound.
• They stratified the cost-effectiveness of the MRI approach by severity of PSA level: less than 2.5 ng/mL, 2.5-4.0 ng/mL, 4.1-10.0 ng/mL, and greater than 10.0 ng/mL.

TAKEAWAY:

• For three of the four PSA levels (2.5-4.0 ng/mL, 4.1-10.0 ng/mL, and greater than 10.0 ng/mL) the combination of MRI plus MRI-guided biopsy was cost effective.
• The MRI-based approach cost $6,000 more than ultrasound for each life-year gained at the highest PSA level of greater than 10.0 ng/mL, which was significantly below the $100,000 threshold.
• At the lowest PSA level of less than 2.5 ng/mL, the difference between MRI and ultrasound was $187,000, which was above the threshold.

IN PRACTICE:

The researchers wrote that there is “a growing consensus that the use of MRI and potential MRI-guided biopsy is cost effective.”

SOURCE:

Ali Jalali, PhD, a health economist at Weill Cornell Medicine, New York, is the senior author of the study. Simulation data come from the National Vital Statistics Report of the Centers for Disease Control and Prevention and the Medicare fee schedule.

LIMITATIONS:

The study is a hypothetical simulation of what could happen under different conditions, not an analysis of data developed over time in clinical practice. It also assumes that PSA levels remain constant over time.

DISCLOSURES:

One author receives grants from Siemens Healthineers for MRI technology development, and another author consults for Promaxo, which develops MRI tools.

A version of this article first appeared on Medscape.com.

Individuals with intraductal papillary mucinous neoplasms (IPMNs) that lack “worrisome or high-risk features” have no greater risk of pancreatic cancer than individuals without IPMNs, based on a retrospective cohort study from Mayo Clinic.

These findings, if validated in a larger population, could challenge current surveillance practices for IPMNs, reported researchers who were led by Shounak Majumder, MD, a gastroenterologist in the pancreas clinic at Mayo Clinic, Rochester, Minn. The study was published in JAMA Network Open.

“Among intraductal papillary mucinous neoplasms (IPMNs) that were Fukuoka negative at baseline, fewer than 10% developed worrisome or high-risk features on follow-up. Pancreatic cancer development in IPMN was a rare event overall,” the authors wrote.

“Current international consensus guidelines for the management of IPMNs recommend image-based surveillance with the aim to detect clinical and imaging features of advanced neoplasia,” the authors wrote. Yet “there are no population-based estimates of the burden of pancreatic cancer in individuals with IPMNs or the proportion of pancreatic cancers that develop from or adjacent to an IPMN.”

Researchers aimed to address this knowledge gap with a population-based cohort study. Drawing data from the Rochester Epidemiology Project, which includes longitudinal medical records from residents of Olmsted County, Minn., investigators identified two cohorts. The first group comprised 2,114 patients 50 years old or older who had undergone abdominal CT scans between 2000 and 2015, among whom 231 (10.9%) had IPMNs. The second cohort included 320 patients diagnosed with pancreatic cancer between 2000 and 2019, among whom 31 (9.8%) had IPMNs.

Further analysis showed that 81% of the patients with IPMNs in the first cohort lacked Fukuoka high-risk or worrisome features. Within this subgroup, the incidence rate of pancreatic cancer per 100 years was not significantly different than among individuals without IPMNs.

“Although the risk of IPMN-PC is has been extensively described, our population-based study further demonstrates that most IPMNs did not progress in Fukuoka stage and did not transform into pancreatic cancer, a similar message was expressed by the current American Gastroenterological Association pancreatic cyst guidelines, published in 2015, and studies published in 2022 and 2016,” the investigators wrote.

Analyzing the cohort of 320 patients with pancreatic cancer showed those with IPMNs had significantly better outcomes than those without IPMNs, including longer survival and lower rate of metastatic disease upon diagnosis. These findings align with previous research, the investigators wrote.

In an accompanying editorial, Stefano Crippa, MD, PhD, of Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, and colleagues offered their perspective on the findings.

“Although results of this study should be validated in larger cohorts, they represent useful clinical data from an unselected population-based cohort that helps challenge current IPMN surveillance policies that recommend lifetime active surveillance for all fit individuals,” they wrote. “Currently, we can use follow-up data from studies like this one to identify patients with IPMNs who are not at risk of progression based on clinical-radiological parameters. We can furthermore start selecting subgroups of patients with limited life expectancy due to age or comorbidities to be considered for surveillance discontinuation.”

Timothy Louis Frankel, MD, a gastrointestinal surgeon at the University of Michigan, Ann Arbor, specializing in malignancies, said the findings are most useful for reassuring patients who have been diagnosed with an IPMN.

“The real take-home message is that in the absence of worrisome features people [with an IPMN] should feel comfortable that their risk is no higher than the general population for developing pancreatic cancer,” Dr. Frankel said in an interview.

Before any changes to surveillance can be considered, however, Dr. Frankel echoed the investigators’ call for a larger study, noting the relatively small population, most of whom (92%) were White.

“We do know that pancreas cancer and pancreas diseases vary significantly by race,” Dr. Frankel said. “So we do need to be a little bit cautious about changing the way that we manage patients based on a fairly homogeneous subset.”

He also pointed out that two patients had IPMNs that developed increased risk over time.

“They actually went from no risk features to having features that put them at risk,” Dr. Frankel said. “Those are patients who were saved by surveillance. So I’m not sure that this study was necessarily designed to let us know if and when we can stop following these lesions.”

Study authors had no relevant disclosures. The editorial writers reported no conflicts of interest.

Individuals with intraductal papillary mucinous neoplasms (IPMNs) that lack “worrisome or high-risk features” have no greater risk of pancreatic cancer than individuals without IPMNs, based on a retrospective cohort study from Mayo Clinic.

These findings, if validated in a larger population, could challenge current surveillance practices for IPMNs, reported researchers who were led by Shounak Majumder, MD, a gastroenterologist in the pancreas clinic at Mayo Clinic, Rochester, Minn. The study was published in JAMA Network Open.

“Among intraductal papillary mucinous neoplasms (IPMNs) that were Fukuoka negative at baseline, fewer than 10% developed worrisome or high-risk features on follow-up. Pancreatic cancer development in IPMN was a rare event overall,” the authors wrote.

“Current international consensus guidelines for the management of IPMNs recommend image-based surveillance with the aim to detect clinical and imaging features of advanced neoplasia,” the authors wrote. Yet “there are no population-based estimates of the burden of pancreatic cancer in individuals with IPMNs or the proportion of pancreatic cancers that develop from or adjacent to an IPMN.”

Researchers aimed to address this knowledge gap with a population-based cohort study. Drawing data from the Rochester Epidemiology Project, which includes longitudinal medical records from residents of Olmsted County, Minn., investigators identified two cohorts. The first group comprised 2,114 patients 50 years old or older who had undergone abdominal CT scans between 2000 and 2015, among whom 231 (10.9%) had IPMNs. The second cohort included 320 patients diagnosed with pancreatic cancer between 2000 and 2019, among whom 31 (9.8%) had IPMNs.

Further analysis showed that 81% of the patients with IPMNs in the first cohort lacked Fukuoka high-risk or worrisome features. Within this subgroup, the incidence rate of pancreatic cancer per 100 years was not significantly different than among individuals without IPMNs.

“Although the risk of IPMN-PC is has been extensively described, our population-based study further demonstrates that most IPMNs did not progress in Fukuoka stage and did not transform into pancreatic cancer, a similar message was expressed by the current American Gastroenterological Association pancreatic cyst guidelines, published in 2015, and studies published in 2022 and 2016,” the investigators wrote.

Analyzing the cohort of 320 patients with pancreatic cancer showed those with IPMNs had significantly better outcomes than those without IPMNs, including longer survival and lower rate of metastatic disease upon diagnosis. These findings align with previous research, the investigators wrote.

In an accompanying editorial, Stefano Crippa, MD, PhD, of Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, and colleagues offered their perspective on the findings.

“Although results of this study should be validated in larger cohorts, they represent useful clinical data from an unselected population-based cohort that helps challenge current IPMN surveillance policies that recommend lifetime active surveillance for all fit individuals,” they wrote. “Currently, we can use follow-up data from studies like this one to identify patients with IPMNs who are not at risk of progression based on clinical-radiological parameters. We can furthermore start selecting subgroups of patients with limited life expectancy due to age or comorbidities to be considered for surveillance discontinuation.”

Timothy Louis Frankel, MD, a gastrointestinal surgeon at the University of Michigan, Ann Arbor, specializing in malignancies, said the findings are most useful for reassuring patients who have been diagnosed with an IPMN.

“The real take-home message is that in the absence of worrisome features people [with an IPMN] should feel comfortable that their risk is no higher than the general population for developing pancreatic cancer,” Dr. Frankel said in an interview.

Before any changes to surveillance can be considered, however, Dr. Frankel echoed the investigators’ call for a larger study, noting the relatively small population, most of whom (92%) were White.

“We do know that pancreas cancer and pancreas diseases vary significantly by race,” Dr. Frankel said. “So we do need to be a little bit cautious about changing the way that we manage patients based on a fairly homogeneous subset.”

He also pointed out that two patients had IPMNs that developed increased risk over time.

“They actually went from no risk features to having features that put them at risk,” Dr. Frankel said. “Those are patients who were saved by surveillance. So I’m not sure that this study was necessarily designed to let us know if and when we can stop following these lesions.”

Study authors had no relevant disclosures. The editorial writers reported no conflicts of interest.

Individuals with intraductal papillary mucinous neoplasms (IPMNs) that lack “worrisome or high-risk features” have no greater risk of pancreatic cancer than individuals without IPMNs, based on a retrospective cohort study from Mayo Clinic.

These findings, if validated in a larger population, could challenge current surveillance practices for IPMNs, reported researchers who were led by Shounak Majumder, MD, a gastroenterologist in the pancreas clinic at Mayo Clinic, Rochester, Minn. The study was published in JAMA Network Open.

“Among intraductal papillary mucinous neoplasms (IPMNs) that were Fukuoka negative at baseline, fewer than 10% developed worrisome or high-risk features on follow-up. Pancreatic cancer development in IPMN was a rare event overall,” the authors wrote.

“Current international consensus guidelines for the management of IPMNs recommend image-based surveillance with the aim to detect clinical and imaging features of advanced neoplasia,” the authors wrote. Yet “there are no population-based estimates of the burden of pancreatic cancer in individuals with IPMNs or the proportion of pancreatic cancers that develop from or adjacent to an IPMN.”

Researchers aimed to address this knowledge gap with a population-based cohort study. Drawing data from the Rochester Epidemiology Project, which includes longitudinal medical records from residents of Olmsted County, Minn., investigators identified two cohorts. The first group comprised 2,114 patients 50 years old or older who had undergone abdominal CT scans between 2000 and 2015, among whom 231 (10.9%) had IPMNs. The second cohort included 320 patients diagnosed with pancreatic cancer between 2000 and 2019, among whom 31 (9.8%) had IPMNs.

Further analysis showed that 81% of the patients with IPMNs in the first cohort lacked Fukuoka high-risk or worrisome features. Within this subgroup, the incidence rate of pancreatic cancer per 100 years was not significantly different than among individuals without IPMNs.

“Although the risk of IPMN-PC is has been extensively described, our population-based study further demonstrates that most IPMNs did not progress in Fukuoka stage and did not transform into pancreatic cancer, a similar message was expressed by the current American Gastroenterological Association pancreatic cyst guidelines, published in 2015, and studies published in 2022 and 2016,” the investigators wrote.

Analyzing the cohort of 320 patients with pancreatic cancer showed those with IPMNs had significantly better outcomes than those without IPMNs, including longer survival and lower rate of metastatic disease upon diagnosis. These findings align with previous research, the investigators wrote.

In an accompanying editorial, Stefano Crippa, MD, PhD, of Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, and colleagues offered their perspective on the findings.

“Although results of this study should be validated in larger cohorts, they represent useful clinical data from an unselected population-based cohort that helps challenge current IPMN surveillance policies that recommend lifetime active surveillance for all fit individuals,” they wrote. “Currently, we can use follow-up data from studies like this one to identify patients with IPMNs who are not at risk of progression based on clinical-radiological parameters. We can furthermore start selecting subgroups of patients with limited life expectancy due to age or comorbidities to be considered for surveillance discontinuation.”

Timothy Louis Frankel, MD, a gastrointestinal surgeon at the University of Michigan, Ann Arbor, specializing in malignancies, said the findings are most useful for reassuring patients who have been diagnosed with an IPMN.

“The real take-home message is that in the absence of worrisome features people [with an IPMN] should feel comfortable that their risk is no higher than the general population for developing pancreatic cancer,” Dr. Frankel said in an interview.

Before any changes to surveillance can be considered, however, Dr. Frankel echoed the investigators’ call for a larger study, noting the relatively small population, most of whom (92%) were White.

“We do know that pancreas cancer and pancreas diseases vary significantly by race,” Dr. Frankel said. “So we do need to be a little bit cautious about changing the way that we manage patients based on a fairly homogeneous subset.”

He also pointed out that two patients had IPMNs that developed increased risk over time.

“They actually went from no risk features to having features that put them at risk,” Dr. Frankel said. “Those are patients who were saved by surveillance. So I’m not sure that this study was necessarily designed to let us know if and when we can stop following these lesions.”

Study authors had no relevant disclosures. The editorial writers reported no conflicts of interest.

The antiseizure drugs levetiracetam (Keppra, Keppra XR, Elepsia XR, Spritam, generic) and clobazam (Onfi, Sympazan, generic) can cause a rare but serious drug hypersensitivity reaction that can be life threatening if not detected and treated promptly, the Food and Drug Administration warns in an alert.

Known as drug reaction with eosinophilia and systemic symptoms (DRESS), it may start as a rash but can quickly progress and cause injury to internal organs, the need for hospitalization, and death, the FDA notes.

A search of the FDA Adverse Event Reporting System (FAERS) and the medical literature through March 2023 identified 32 serious cases of DRESS worldwide that were associated with levetiracetam.

Three cases occurred in the United States, and 29 occurred abroad. In all 32 cases, the patients were hospitalized and received medical treatment; in 2 cases, the patients died.

The median time to onset of DRESS in the levetiracetam cases was 24 days; times ranged from 7 to 170 days. The reported signs and symptoms included skin rash (n = 22), fever (n = 20), eosinophilia (n = 17), lymph node swelling (n = 9), and atypical lymphocytes (n = 4).

Twenty-two levetiracetam-associated cases of DRESS involved injury to one or more organs, including the liver, lungs, kidneys, and gallbladder.

In 25 of the 29 cases for which information on treatment discontinuation was available, DRESS symptoms resolved when levetiracetam was discontinued.

As for clobazam, a search of FAERS and the medical literature through July 2023 identified 10 serious cases of DRESS worldwide – 1 in the United States and 9 abroad. All 10 patients were hospitalized and received medical treatment. No deaths were reported.

The median time to onset of clobazam-associated DRESS was 21.5 days (range, 7-103 days). The reported signs and symptoms included skin rash (n = 10), fever (n = 8), eosinophilia (n = 7), facial swelling (n = 7), leukocytosis (n = 4), lymph node swelling (n = 4), and leukopenia/thrombocytopenia (n = 1).

In nine cases, there was injury to one or more organs, including the liver, kidneys, and gastrointestinal tract.

DRESS symptoms resolved in all 10 cases when treatment with clobazam was stopped. DRESS and other serious skin reactions reported with clobazam, a benzodiazepine, have not generally been associated with other benzodiazepines, the FDA notes.

Label updates

As a result of these cases, warnings about the risk of DRESS will be added to the prescribing information and patient medication guides for these medicines, the FDA announced.

“Health care professionals should be aware that prompt recognition and early treatment is important for improving DRESS outcomes and decreasing mortality,” the FDA said.

They noted that diagnosis is often difficult because early signs and symptoms, such as fever and swollen lymph nodes, may be present without evidence of a rash.

DRESS may develop 2-8 weeks after starting levetiracetam or clobazam. Symptoms and intensity can vary widely.

DRESS can also be confused with other serious skin reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis.

The FDA says patients should be advised of the signs and symptoms of DRESS and be told to stop taking the medicine and seek immediate medical attention if DRESS is suspected during treatment with levetiracetam or clobazam.

Adverse reactions with these medications should be reported to the FDA’s MedWatch program.

A version of this article appeared on Medscape.com.

The antiseizure drugs levetiracetam (Keppra, Keppra XR, Elepsia XR, Spritam, generic) and clobazam (Onfi, Sympazan, generic) can cause a rare but serious drug hypersensitivity reaction that can be life threatening if not detected and treated promptly, the Food and Drug Administration warns in an alert.

Known as drug reaction with eosinophilia and systemic symptoms (DRESS), it may start as a rash but can quickly progress and cause injury to internal organs, the need for hospitalization, and death, the FDA notes.

A search of the FDA Adverse Event Reporting System (FAERS) and the medical literature through March 2023 identified 32 serious cases of DRESS worldwide that were associated with levetiracetam.

Three cases occurred in the United States, and 29 occurred abroad. In all 32 cases, the patients were hospitalized and received medical treatment; in 2 cases, the patients died.

The median time to onset of DRESS in the levetiracetam cases was 24 days; times ranged from 7 to 170 days. The reported signs and symptoms included skin rash (n = 22), fever (n = 20), eosinophilia (n = 17), lymph node swelling (n = 9), and atypical lymphocytes (n = 4).

Twenty-two levetiracetam-associated cases of DRESS involved injury to one or more organs, including the liver, lungs, kidneys, and gallbladder.

In 25 of the 29 cases for which information on treatment discontinuation was available, DRESS symptoms resolved when levetiracetam was discontinued.

As for clobazam, a search of FAERS and the medical literature through July 2023 identified 10 serious cases of DRESS worldwide – 1 in the United States and 9 abroad. All 10 patients were hospitalized and received medical treatment. No deaths were reported.

The median time to onset of clobazam-associated DRESS was 21.5 days (range, 7-103 days). The reported signs and symptoms included skin rash (n = 10), fever (n = 8), eosinophilia (n = 7), facial swelling (n = 7), leukocytosis (n = 4), lymph node swelling (n = 4), and leukopenia/thrombocytopenia (n = 1).

In nine cases, there was injury to one or more organs, including the liver, kidneys, and gastrointestinal tract.

DRESS symptoms resolved in all 10 cases when treatment with clobazam was stopped. DRESS and other serious skin reactions reported with clobazam, a benzodiazepine, have not generally been associated with other benzodiazepines, the FDA notes.

Label updates

As a result of these cases, warnings about the risk of DRESS will be added to the prescribing information and patient medication guides for these medicines, the FDA announced.

“Health care professionals should be aware that prompt recognition and early treatment is important for improving DRESS outcomes and decreasing mortality,” the FDA said.

They noted that diagnosis is often difficult because early signs and symptoms, such as fever and swollen lymph nodes, may be present without evidence of a rash.

DRESS may develop 2-8 weeks after starting levetiracetam or clobazam. Symptoms and intensity can vary widely.

DRESS can also be confused with other serious skin reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis.

The FDA says patients should be advised of the signs and symptoms of DRESS and be told to stop taking the medicine and seek immediate medical attention if DRESS is suspected during treatment with levetiracetam or clobazam.

Adverse reactions with these medications should be reported to the FDA’s MedWatch program.

A version of this article appeared on Medscape.com.

The antiseizure drugs levetiracetam (Keppra, Keppra XR, Elepsia XR, Spritam, generic) and clobazam (Onfi, Sympazan, generic) can cause a rare but serious drug hypersensitivity reaction that can be life threatening if not detected and treated promptly, the Food and Drug Administration warns in an alert.

Known as drug reaction with eosinophilia and systemic symptoms (DRESS), it may start as a rash but can quickly progress and cause injury to internal organs, the need for hospitalization, and death, the FDA notes.

A search of the FDA Adverse Event Reporting System (FAERS) and the medical literature through March 2023 identified 32 serious cases of DRESS worldwide that were associated with levetiracetam.

Three cases occurred in the United States, and 29 occurred abroad. In all 32 cases, the patients were hospitalized and received medical treatment; in 2 cases, the patients died.

The median time to onset of DRESS in the levetiracetam cases was 24 days; times ranged from 7 to 170 days. The reported signs and symptoms included skin rash (n = 22), fever (n = 20), eosinophilia (n = 17), lymph node swelling (n = 9), and atypical lymphocytes (n = 4).

Twenty-two levetiracetam-associated cases of DRESS involved injury to one or more organs, including the liver, lungs, kidneys, and gallbladder.

In 25 of the 29 cases for which information on treatment discontinuation was available, DRESS symptoms resolved when levetiracetam was discontinued.

As for clobazam, a search of FAERS and the medical literature through July 2023 identified 10 serious cases of DRESS worldwide – 1 in the United States and 9 abroad. All 10 patients were hospitalized and received medical treatment. No deaths were reported.

The median time to onset of clobazam-associated DRESS was 21.5 days (range, 7-103 days). The reported signs and symptoms included skin rash (n = 10), fever (n = 8), eosinophilia (n = 7), facial swelling (n = 7), leukocytosis (n = 4), lymph node swelling (n = 4), and leukopenia/thrombocytopenia (n = 1).

In nine cases, there was injury to one or more organs, including the liver, kidneys, and gastrointestinal tract.

DRESS symptoms resolved in all 10 cases when treatment with clobazam was stopped. DRESS and other serious skin reactions reported with clobazam, a benzodiazepine, have not generally been associated with other benzodiazepines, the FDA notes.

Label updates

As a result of these cases, warnings about the risk of DRESS will be added to the prescribing information and patient medication guides for these medicines, the FDA announced.

“Health care professionals should be aware that prompt recognition and early treatment is important for improving DRESS outcomes and decreasing mortality,” the FDA said.

They noted that diagnosis is often difficult because early signs and symptoms, such as fever and swollen lymph nodes, may be present without evidence of a rash.

DRESS may develop 2-8 weeks after starting levetiracetam or clobazam. Symptoms and intensity can vary widely.

DRESS can also be confused with other serious skin reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis.

The FDA says patients should be advised of the signs and symptoms of DRESS and be told to stop taking the medicine and seek immediate medical attention if DRESS is suspected during treatment with levetiracetam or clobazam.

Adverse reactions with these medications should be reported to the FDA’s MedWatch program.

A version of this article appeared on Medscape.com.

TOPLINE:

An international expert consensus offers guidance to diagnose, assess, and treat adult patients experiencing drug reaction with eosinophilia and systemic symptoms (DRESS).

METHODOLOGY:

Data on the evaluation, assessment, and treatment of the rare but potentially life-threatening drug hypersensitivity reaction are lacking.

To support clinicians in diagnosing and managing DRESS, a steering committee conducted a literature review to examine current research, identify evidence, and develop consensus statements. They invited experts from 21 countries across four continents to participate in a Delphi consensus process.

An international panel of 54 experts (including 45 dermatologists) initially assessed 100 statements related to baseline workup, severity of the condition, and treatment. Two more statements were added in the second round.

After revisions and the second round, the group reached consensus for 93 statements overall.

TAKEAWAY:

The statements generating the most disagreement involved diagnosis. The group ultimately supported the value of measuring the viral load of Epstein-Barr virus, cytomegalovirus, and human herpesvirus 6 in all patients with suspected DRESS. The group also agreed on screening for hepatitis A, B, and C in cases of liver involvement and screening for hepatitis B and C before starting systemic therapy.

The group agreed with previous severity criteria that differentiate between mild, moderate, and severe DRESS based on the extent of liver, kidney, and blood involvement and the damage of other organs.

Consensus on treatment was reached for all 12 relevant statements in the first Delphi round. Recommendations included the use of corticosteroids and immediate discontinuation of the drugs causing the reaction.

IN PRACTICE:

“This Delphi exercise aimed to provide a common ground of consensus,” the authors noted. However, “each of the addressed categories needs more in-depth follow-up studies to improve the clinical management of patients.”

SOURCE:

The DRESS Delphi consensus group conducted its exercise under the leadership of Marie-Charlotte Brüggen, MD, of the University Hospital of Zürich. The consensus was published online in the JAMA Dermatology.

LIMITATIONS:

Published evidence was limited because of the low prevalence of DRESS. The consensus statements should therefore be considered with caution and in the context of a clinician’s expertise and available resources. Research gaps also persist in how DRESS may vary with region and ethnicity. The severity thresholds need validation in a revised multicenter statement.

DISCLOSURES:

The consensus review received no outside funding. Dr. Brüggen disclosed relationships with the Swiss National Science Foundation, Christine Kühne – Center for Allergy Research and Education, FreeNovation, LEO Foundation, Olga Mayenfisch Foundation, University of Zürich, LEO Pharma, Pierre Fabre Eczema Foundation, Eli Lilly, AbbVie, GSK, and AstraZeneca. Coauthors disclosed relationships with multiple pharmaceutical companies, foundations, and medical publishing companies.

A version of this article appeared on Medscape.com.

TOPLINE:

An international expert consensus offers guidance to diagnose, assess, and treat adult patients experiencing drug reaction with eosinophilia and systemic symptoms (DRESS).

METHODOLOGY:

Data on the evaluation, assessment, and treatment of the rare but potentially life-threatening drug hypersensitivity reaction are lacking.

To support clinicians in diagnosing and managing DRESS, a steering committee conducted a literature review to examine current research, identify evidence, and develop consensus statements. They invited experts from 21 countries across four continents to participate in a Delphi consensus process.

An international panel of 54 experts (including 45 dermatologists) initially assessed 100 statements related to baseline workup, severity of the condition, and treatment. Two more statements were added in the second round.

After revisions and the second round, the group reached consensus for 93 statements overall.

TAKEAWAY:

The statements generating the most disagreement involved diagnosis. The group ultimately supported the value of measuring the viral load of Epstein-Barr virus, cytomegalovirus, and human herpesvirus 6 in all patients with suspected DRESS. The group also agreed on screening for hepatitis A, B, and C in cases of liver involvement and screening for hepatitis B and C before starting systemic therapy.

The group agreed with previous severity criteria that differentiate between mild, moderate, and severe DRESS based on the extent of liver, kidney, and blood involvement and the damage of other organs.

Consensus on treatment was reached for all 12 relevant statements in the first Delphi round. Recommendations included the use of corticosteroids and immediate discontinuation of the drugs causing the reaction.

IN PRACTICE:

“This Delphi exercise aimed to provide a common ground of consensus,” the authors noted. However, “each of the addressed categories needs more in-depth follow-up studies to improve the clinical management of patients.”

SOURCE:

The DRESS Delphi consensus group conducted its exercise under the leadership of Marie-Charlotte Brüggen, MD, of the University Hospital of Zürich. The consensus was published online in the JAMA Dermatology.

LIMITATIONS:

Published evidence was limited because of the low prevalence of DRESS. The consensus statements should therefore be considered with caution and in the context of a clinician’s expertise and available resources. Research gaps also persist in how DRESS may vary with region and ethnicity. The severity thresholds need validation in a revised multicenter statement.

DISCLOSURES:

The consensus review received no outside funding. Dr. Brüggen disclosed relationships with the Swiss National Science Foundation, Christine Kühne – Center for Allergy Research and Education, FreeNovation, LEO Foundation, Olga Mayenfisch Foundation, University of Zürich, LEO Pharma, Pierre Fabre Eczema Foundation, Eli Lilly, AbbVie, GSK, and AstraZeneca. Coauthors disclosed relationships with multiple pharmaceutical companies, foundations, and medical publishing companies.

A version of this article appeared on Medscape.com.

TOPLINE:

An international expert consensus offers guidance to diagnose, assess, and treat adult patients experiencing drug reaction with eosinophilia and systemic symptoms (DRESS).

METHODOLOGY:

Data on the evaluation, assessment, and treatment of the rare but potentially life-threatening drug hypersensitivity reaction are lacking.

To support clinicians in diagnosing and managing DRESS, a steering committee conducted a literature review to examine current research, identify evidence, and develop consensus statements. They invited experts from 21 countries across four continents to participate in a Delphi consensus process.

An international panel of 54 experts (including 45 dermatologists) initially assessed 100 statements related to baseline workup, severity of the condition, and treatment. Two more statements were added in the second round.

After revisions and the second round, the group reached consensus for 93 statements overall.

TAKEAWAY:

The statements generating the most disagreement involved diagnosis. The group ultimately supported the value of measuring the viral load of Epstein-Barr virus, cytomegalovirus, and human herpesvirus 6 in all patients with suspected DRESS. The group also agreed on screening for hepatitis A, B, and C in cases of liver involvement and screening for hepatitis B and C before starting systemic therapy.

The group agreed with previous severity criteria that differentiate between mild, moderate, and severe DRESS based on the extent of liver, kidney, and blood involvement and the damage of other organs.

Consensus on treatment was reached for all 12 relevant statements in the first Delphi round. Recommendations included the use of corticosteroids and immediate discontinuation of the drugs causing the reaction.

IN PRACTICE:

“This Delphi exercise aimed to provide a common ground of consensus,” the authors noted. However, “each of the addressed categories needs more in-depth follow-up studies to improve the clinical management of patients.”

SOURCE:

The DRESS Delphi consensus group conducted its exercise under the leadership of Marie-Charlotte Brüggen, MD, of the University Hospital of Zürich. The consensus was published online in the JAMA Dermatology.

LIMITATIONS:

Published evidence was limited because of the low prevalence of DRESS. The consensus statements should therefore be considered with caution and in the context of a clinician’s expertise and available resources. Research gaps also persist in how DRESS may vary with region and ethnicity. The severity thresholds need validation in a revised multicenter statement.

DISCLOSURES:

The consensus review received no outside funding. Dr. Brüggen disclosed relationships with the Swiss National Science Foundation, Christine Kühne – Center for Allergy Research and Education, FreeNovation, LEO Foundation, Olga Mayenfisch Foundation, University of Zürich, LEO Pharma, Pierre Fabre Eczema Foundation, Eli Lilly, AbbVie, GSK, and AstraZeneca. Coauthors disclosed relationships with multiple pharmaceutical companies, foundations, and medical publishing companies.

A version of this article appeared on Medscape.com.

The Food and Drug Administration approved a new colony-stimulating factor, efbemalenograstim alfa (Ryzneuta, Evive Biotech), to decrease the incidence of infection, as manifested by febrile neutropenia, in adults with nonmyeloid malignancies receiving myelosuppressive anticancer drugs.

Efbemalenograstim joins other agents already on the U.S. market, including pegfilgrastim (Neulasta), that aim to reduce the incidence of chemotherapy-induced febrile neutropenia.

The approval of efbemalenograstim was based on two randomized trials. The first included 122 women with either metastatic or nonmetastatic breast cancer who were receiving doxorubicin and docetaxel. These patients were randomly assigned to receive either one subcutaneous injection of efbemalenograstim or placebo on the second day of their first chemotherapy cycle. All patients received efbemalenograstim on the second day of cycles two through four.

The mean duration of grade 4 neutropenia in the first cycle was 1.4 days with efbemalenograstim versus 4.3 days with placebo. Only 4.8% of patients who received efbemalenograstim experienced chemotherapy-induced febrile neutropenia, compared with 25.6% who received the placebo.

The new agent went up against pegfilgrastim in the second trial, which included 393 women who received docetaxel and cyclophosphamide as treatment for nonmetastatic breast cancer. These patients were randomly assigned to receive either a single subcutaneous injection of efbemalenograstim or pegfilgrastim on the second day of each cycle.

During the first cycle, patients in both arms of the trial experienced a mean of 0.2 days of grade 4 neutropenia.

The most common side effects associated with efbemalenograstim were nausea, anemia, and thrombocytopenia. Similar to pegfilgrastim’s label, efbemalenograstim’s label warns of possible splenic rupture, respiratory distress syndrome, sickle cell crisis, and other serious adverse events.

The FDA recommends a dose of 20 mg subcutaneous once per chemotherapy cycle.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration approved a new colony-stimulating factor, efbemalenograstim alfa (Ryzneuta, Evive Biotech), to decrease the incidence of infection, as manifested by febrile neutropenia, in adults with nonmyeloid malignancies receiving myelosuppressive anticancer drugs.

Efbemalenograstim joins other agents already on the U.S. market, including pegfilgrastim (Neulasta), that aim to reduce the incidence of chemotherapy-induced febrile neutropenia.

The approval of efbemalenograstim was based on two randomized trials. The first included 122 women with either metastatic or nonmetastatic breast cancer who were receiving doxorubicin and docetaxel. These patients were randomly assigned to receive either one subcutaneous injection of efbemalenograstim or placebo on the second day of their first chemotherapy cycle. All patients received efbemalenograstim on the second day of cycles two through four.

The mean duration of grade 4 neutropenia in the first cycle was 1.4 days with efbemalenograstim versus 4.3 days with placebo. Only 4.8% of patients who received efbemalenograstim experienced chemotherapy-induced febrile neutropenia, compared with 25.6% who received the placebo.

The new agent went up against pegfilgrastim in the second trial, which included 393 women who received docetaxel and cyclophosphamide as treatment for nonmetastatic breast cancer. These patients were randomly assigned to receive either a single subcutaneous injection of efbemalenograstim or pegfilgrastim on the second day of each cycle.

During the first cycle, patients in both arms of the trial experienced a mean of 0.2 days of grade 4 neutropenia.

The most common side effects associated with efbemalenograstim were nausea, anemia, and thrombocytopenia. Similar to pegfilgrastim’s label, efbemalenograstim’s label warns of possible splenic rupture, respiratory distress syndrome, sickle cell crisis, and other serious adverse events.

The FDA recommends a dose of 20 mg subcutaneous once per chemotherapy cycle.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration approved a new colony-stimulating factor, efbemalenograstim alfa (Ryzneuta, Evive Biotech), to decrease the incidence of infection, as manifested by febrile neutropenia, in adults with nonmyeloid malignancies receiving myelosuppressive anticancer drugs.

Efbemalenograstim joins other agents already on the U.S. market, including pegfilgrastim (Neulasta), that aim to reduce the incidence of chemotherapy-induced febrile neutropenia.

The approval of efbemalenograstim was based on two randomized trials. The first included 122 women with either metastatic or nonmetastatic breast cancer who were receiving doxorubicin and docetaxel. These patients were randomly assigned to receive either one subcutaneous injection of efbemalenograstim or placebo on the second day of their first chemotherapy cycle. All patients received efbemalenograstim on the second day of cycles two through four.

The mean duration of grade 4 neutropenia in the first cycle was 1.4 days with efbemalenograstim versus 4.3 days with placebo. Only 4.8% of patients who received efbemalenograstim experienced chemotherapy-induced febrile neutropenia, compared with 25.6% who received the placebo.

The new agent went up against pegfilgrastim in the second trial, which included 393 women who received docetaxel and cyclophosphamide as treatment for nonmetastatic breast cancer. These patients were randomly assigned to receive either a single subcutaneous injection of efbemalenograstim or pegfilgrastim on the second day of each cycle.

During the first cycle, patients in both arms of the trial experienced a mean of 0.2 days of grade 4 neutropenia.

The most common side effects associated with efbemalenograstim were nausea, anemia, and thrombocytopenia. Similar to pegfilgrastim’s label, efbemalenograstim’s label warns of possible splenic rupture, respiratory distress syndrome, sickle cell crisis, and other serious adverse events.

The FDA recommends a dose of 20 mg subcutaneous once per chemotherapy cycle.

A version of this article first appeared on Medscape.com.

CHICAGO – The US Department of Veterans Affairs (VA) has developed clinical pathways to guide its clinicians through cancer care, but they should not be considered mandatory strategies, a top VA cancer director told colleagues at the 2023 annual meeting of the Association of VA Hematology/Oncology.

“They’re not a cookbook for how to practice oncology,” said Michael Kelley, MD, the VA National Program Director for Oncology, Professor of Medicine at Duke University, and Chief of Hematology and Oncology at the Durham VA Medical Center. “You cannot look at the pathway and think that you know how to practice. It is a preferred-decision flow map—not a requirement to do that. We expect that all providers will be off the pathways some of the time and most of the time, they will be on there.”

The VA has an extensive series of clinical pathways in oncology that are designed to help clinicians navigate through the treatment of 20 types of cancer, including common types—breast, lung, and colon—and rarer types, such as salivary gland and biliary tract cancer. Many of the pathways have been updated within just the past few months, and more are in the works.

The pathways are developed through subject-matter expert groups made up of experts from National Cancer Institute–designated cancer centers, Kelley said. “The pathway is published as a PDF document on internally and externally facing websites, then it's built into the medical record system.” Clinicians who diverge from the pathways have to note this in the health record system, enter reasons why, and provide the alternative care strategy, Kelley explained.

Moving forward, the VA is “committed to doing a formal review of all the pathways at least quarterly, and we will do ad hoc reviews and alterations as information merits.” He said, “There are hundreds of oncology providers in the VA, and we want everyone to have an opportunity to have input. That's your opportunity: We do read every comment, and we'll actually generate a response to every comment.”

CHICAGO – The US Department of Veterans Affairs (VA) has developed clinical pathways to guide its clinicians through cancer care, but they should not be considered mandatory strategies, a top VA cancer director told colleagues at the 2023 annual meeting of the Association of VA Hematology/Oncology.

“They’re not a cookbook for how to practice oncology,” said Michael Kelley, MD, the VA National Program Director for Oncology, Professor of Medicine at Duke University, and Chief of Hematology and Oncology at the Durham VA Medical Center. “You cannot look at the pathway and think that you know how to practice. It is a preferred-decision flow map—not a requirement to do that. We expect that all providers will be off the pathways some of the time and most of the time, they will be on there.”

The VA has an extensive series of clinical pathways in oncology that are designed to help clinicians navigate through the treatment of 20 types of cancer, including common types—breast, lung, and colon—and rarer types, such as salivary gland and biliary tract cancer. Many of the pathways have been updated within just the past few months, and more are in the works.

The pathways are developed through subject-matter expert groups made up of experts from National Cancer Institute–designated cancer centers, Kelley said. “The pathway is published as a PDF document on internally and externally facing websites, then it's built into the medical record system.” Clinicians who diverge from the pathways have to note this in the health record system, enter reasons why, and provide the alternative care strategy, Kelley explained.

Moving forward, the VA is “committed to doing a formal review of all the pathways at least quarterly, and we will do ad hoc reviews and alterations as information merits.” He said, “There are hundreds of oncology providers in the VA, and we want everyone to have an opportunity to have input. That's your opportunity: We do read every comment, and we'll actually generate a response to every comment.”

CHICAGO – The US Department of Veterans Affairs (VA) has developed clinical pathways to guide its clinicians through cancer care, but they should not be considered mandatory strategies, a top VA cancer director told colleagues at the 2023 annual meeting of the Association of VA Hematology/Oncology.

“They’re not a cookbook for how to practice oncology,” said Michael Kelley, MD, the VA National Program Director for Oncology, Professor of Medicine at Duke University, and Chief of Hematology and Oncology at the Durham VA Medical Center. “You cannot look at the pathway and think that you know how to practice. It is a preferred-decision flow map—not a requirement to do that. We expect that all providers will be off the pathways some of the time and most of the time, they will be on there.”

The VA has an extensive series of clinical pathways in oncology that are designed to help clinicians navigate through the treatment of 20 types of cancer, including common types—breast, lung, and colon—and rarer types, such as salivary gland and biliary tract cancer. Many of the pathways have been updated within just the past few months, and more are in the works.

The pathways are developed through subject-matter expert groups made up of experts from National Cancer Institute–designated cancer centers, Kelley said. “The pathway is published as a PDF document on internally and externally facing websites, then it's built into the medical record system.” Clinicians who diverge from the pathways have to note this in the health record system, enter reasons why, and provide the alternative care strategy, Kelley explained.

Moving forward, the VA is “committed to doing a formal review of all the pathways at least quarterly, and we will do ad hoc reviews and alterations as information merits.” He said, “There are hundreds of oncology providers in the VA, and we want everyone to have an opportunity to have input. That's your opportunity: We do read every comment, and we'll actually generate a response to every comment.”