Here are the stories our MDedge editors across specialties think you need to know about today:

ED visits drop for life-threatening conditions

Emergency department visits for myocardial infarction, stroke, and hyperglycemic crisis dropped substantially in the 10 weeks after COVID-19 was declared a national emergency, according to new research from the Centers for Disease Control and Prevention.

Compared with the 10-week period from Jan. 5 to March 14, ED visits were down by 23% for MI, 20% for stroke, and 10% for hyperglycemic crisis from March 15 to May 23.

“A short-term decline of this magnitude … is biologically implausible for MI and stroke, especially for older adults, and unlikely for hyperglycemic crisis, and the finding suggests that patients with these conditions either could not access care or were delaying or avoiding seeking care during the early pandemic period,” the researchers wrote in the Morbidity and Mortality Weekly Report. Read more.
 

Expert recommendations for pediatric COVID-19 imaging

A team of pulmonologists has synthesized the clinical and imaging characteristics of COVID-19 in children, and has issued recommendations for ordering imaging studies in suspected cases of the infection.

Current recommendations from the American College of Radiology (ACR) do not include chest computed tomography (CT) or chest radiography (CXR) as an upfront test to diagnose pediatric COVID-19, but the tests may still have a role in clinical monitoring, especially in patients with a moderate to severe disease course. The potential benefits of utilizing radiologic evaluation – such as establishing a baseline for monitoring disease progression – must be balanced with potential drawbacks, including radiation exposure and reduced availability of imaging resources owing to necessary cleaning and air turnover time.

Based on the most recent international guidelines for pediatric COVID-19 patient management, the authors developed an algorithm for performing imaging studies in suspected cases of COVID-19 pneumonia. The purpose of the tool is to support clinical decision-making around the utilization of CXR and CT to evaluate pediatric COVID-19 pneumonia. “The step by step algorithm addresses the selection, sequence and timing of imaging studies with multiple images illustrating key findings of COVID-19 pneumonia in the pediatric age group,” said Mary Cataletto, MD, of NYU Langone Health in Mineola, N.Y. Read more.

Cortisol levels on COVID-19 admission may be a marker of severity

Patients with COVID-19 who have high levels of the steroid hormone cortisol on admission to the hospital have a substantially increased risk of dying, according to new study findings.

Researchers assessed 535 patients admitted to major London hospitals. Of these, 403 patients were diagnosed with COVID-19 based on a positive result on real-time polymerase chain reaction testing or a strong clinical and radiological suspicion, despite a negative test. Mean cortisol concentrations in patients with COVID-19 were significantly higher than those not diagnosed with the virus and as of May 8, significantly more patients with COVID-19 died than those without (27.8% vs 6.8%).

Measuring cortisol on admission is potentially “another simple marker to use alongside oxygen saturation levels to help us identify which patients need to be admitted immediately, and which may not,” said Waljit S. Dhillo, MBBS, PhD, head of the division of diabetes, endocrinology and metabolism at Imperial College London.

“Having an early indicator of which patients may deteriorate more quickly will help us with providing the best level of care as quickly as possible. In addition, we can also take cortisol levels into account when we are working out how best to treat our patients,” he said. Read more.

Normal-weight prediabetes patients can benefit from lifestyle changes

Adults of normal weight with prediabetes may derive at least as much benefit from lifestyle health coaching programs as adults who are overweight or obese, results of a recent nonrandomized, real-world study show.

Fasting plasma glucose (FPG) normalized in about 63% of prediabetic adults with normal body mass index (BMI) participating in a personalized coaching program that emphasized exercise, nutrition, and weight management. In contrast, FPG normalized in about 52% of overweight and 44% of obese prediabetic individuals participating in the program.

“It is interesting to note that, although the normal weight group lost the least amount of weight, they still benefited from the lifestyle health coaching program... having a resultant greatest decrease in fasting plasma glucose and normalization to a range of someone without prediabetes,” said researcher Mandy Salmon, MS, a medical student at the University of Pennsylvania, Philadelphia. She presented the findings at the virtual annual scientific sessions of the American Diabetes Association. Read more.

Diabetes-related amputations rise in older adults

The recent resurgence in diabetes-related lower-extremity amputations in the United States is not limited to younger adults, according to the author of a recent study that documents similar increases among an older population of Medicare beneficiaries.

While the rate of amputations fell among these older adults from 2000 to 2009, it increased significantly from 2009 to 2017, albeit at a “less severe rate” than recently reported in younger populations, according to study investigator Jessica Harding, PhD, an assistant professor in the department of surgery at Emory University, Atlanta. Dr. Harding reported the results at the virtual annual scientific sessions of the American Diabetes Association.

The rate of nontraumatic lower extremity amputation (NLEA) was ticking upward by more than 1% per year over the 2009-2017 period. Read more.

For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.

Here are the stories our MDedge editors across specialties think you need to know about today:

ED visits drop for life-threatening conditions

Emergency department visits for myocardial infarction, stroke, and hyperglycemic crisis dropped substantially in the 10 weeks after COVID-19 was declared a national emergency, according to new research from the Centers for Disease Control and Prevention.

Compared with the 10-week period from Jan. 5 to March 14, ED visits were down by 23% for MI, 20% for stroke, and 10% for hyperglycemic crisis from March 15 to May 23.

“A short-term decline of this magnitude … is biologically implausible for MI and stroke, especially for older adults, and unlikely for hyperglycemic crisis, and the finding suggests that patients with these conditions either could not access care or were delaying or avoiding seeking care during the early pandemic period,” the researchers wrote in the Morbidity and Mortality Weekly Report. Read more.
 

Expert recommendations for pediatric COVID-19 imaging

A team of pulmonologists has synthesized the clinical and imaging characteristics of COVID-19 in children, and has issued recommendations for ordering imaging studies in suspected cases of the infection.

Current recommendations from the American College of Radiology (ACR) do not include chest computed tomography (CT) or chest radiography (CXR) as an upfront test to diagnose pediatric COVID-19, but the tests may still have a role in clinical monitoring, especially in patients with a moderate to severe disease course. The potential benefits of utilizing radiologic evaluation – such as establishing a baseline for monitoring disease progression – must be balanced with potential drawbacks, including radiation exposure and reduced availability of imaging resources owing to necessary cleaning and air turnover time.

Based on the most recent international guidelines for pediatric COVID-19 patient management, the authors developed an algorithm for performing imaging studies in suspected cases of COVID-19 pneumonia. The purpose of the tool is to support clinical decision-making around the utilization of CXR and CT to evaluate pediatric COVID-19 pneumonia. “The step by step algorithm addresses the selection, sequence and timing of imaging studies with multiple images illustrating key findings of COVID-19 pneumonia in the pediatric age group,” said Mary Cataletto, MD, of NYU Langone Health in Mineola, N.Y. Read more.

Cortisol levels on COVID-19 admission may be a marker of severity

Patients with COVID-19 who have high levels of the steroid hormone cortisol on admission to the hospital have a substantially increased risk of dying, according to new study findings.

Researchers assessed 535 patients admitted to major London hospitals. Of these, 403 patients were diagnosed with COVID-19 based on a positive result on real-time polymerase chain reaction testing or a strong clinical and radiological suspicion, despite a negative test. Mean cortisol concentrations in patients with COVID-19 were significantly higher than those not diagnosed with the virus and as of May 8, significantly more patients with COVID-19 died than those without (27.8% vs 6.8%).

Measuring cortisol on admission is potentially “another simple marker to use alongside oxygen saturation levels to help us identify which patients need to be admitted immediately, and which may not,” said Waljit S. Dhillo, MBBS, PhD, head of the division of diabetes, endocrinology and metabolism at Imperial College London.

“Having an early indicator of which patients may deteriorate more quickly will help us with providing the best level of care as quickly as possible. In addition, we can also take cortisol levels into account when we are working out how best to treat our patients,” he said. Read more.

Normal-weight prediabetes patients can benefit from lifestyle changes

Adults of normal weight with prediabetes may derive at least as much benefit from lifestyle health coaching programs as adults who are overweight or obese, results of a recent nonrandomized, real-world study show.

Fasting plasma glucose (FPG) normalized in about 63% of prediabetic adults with normal body mass index (BMI) participating in a personalized coaching program that emphasized exercise, nutrition, and weight management. In contrast, FPG normalized in about 52% of overweight and 44% of obese prediabetic individuals participating in the program.

“It is interesting to note that, although the normal weight group lost the least amount of weight, they still benefited from the lifestyle health coaching program... having a resultant greatest decrease in fasting plasma glucose and normalization to a range of someone without prediabetes,” said researcher Mandy Salmon, MS, a medical student at the University of Pennsylvania, Philadelphia. She presented the findings at the virtual annual scientific sessions of the American Diabetes Association. Read more.

Diabetes-related amputations rise in older adults

The recent resurgence in diabetes-related lower-extremity amputations in the United States is not limited to younger adults, according to the author of a recent study that documents similar increases among an older population of Medicare beneficiaries.

While the rate of amputations fell among these older adults from 2000 to 2009, it increased significantly from 2009 to 2017, albeit at a “less severe rate” than recently reported in younger populations, according to study investigator Jessica Harding, PhD, an assistant professor in the department of surgery at Emory University, Atlanta. Dr. Harding reported the results at the virtual annual scientific sessions of the American Diabetes Association.

The rate of nontraumatic lower extremity amputation (NLEA) was ticking upward by more than 1% per year over the 2009-2017 period. Read more.

For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.

Here are the stories our MDedge editors across specialties think you need to know about today:

ED visits drop for life-threatening conditions

Emergency department visits for myocardial infarction, stroke, and hyperglycemic crisis dropped substantially in the 10 weeks after COVID-19 was declared a national emergency, according to new research from the Centers for Disease Control and Prevention.

Compared with the 10-week period from Jan. 5 to March 14, ED visits were down by 23% for MI, 20% for stroke, and 10% for hyperglycemic crisis from March 15 to May 23.

“A short-term decline of this magnitude … is biologically implausible for MI and stroke, especially for older adults, and unlikely for hyperglycemic crisis, and the finding suggests that patients with these conditions either could not access care or were delaying or avoiding seeking care during the early pandemic period,” the researchers wrote in the Morbidity and Mortality Weekly Report. Read more.
 

Expert recommendations for pediatric COVID-19 imaging

A team of pulmonologists has synthesized the clinical and imaging characteristics of COVID-19 in children, and has issued recommendations for ordering imaging studies in suspected cases of the infection.

Current recommendations from the American College of Radiology (ACR) do not include chest computed tomography (CT) or chest radiography (CXR) as an upfront test to diagnose pediatric COVID-19, but the tests may still have a role in clinical monitoring, especially in patients with a moderate to severe disease course. The potential benefits of utilizing radiologic evaluation – such as establishing a baseline for monitoring disease progression – must be balanced with potential drawbacks, including radiation exposure and reduced availability of imaging resources owing to necessary cleaning and air turnover time.

Based on the most recent international guidelines for pediatric COVID-19 patient management, the authors developed an algorithm for performing imaging studies in suspected cases of COVID-19 pneumonia. The purpose of the tool is to support clinical decision-making around the utilization of CXR and CT to evaluate pediatric COVID-19 pneumonia. “The step by step algorithm addresses the selection, sequence and timing of imaging studies with multiple images illustrating key findings of COVID-19 pneumonia in the pediatric age group,” said Mary Cataletto, MD, of NYU Langone Health in Mineola, N.Y. Read more.

Cortisol levels on COVID-19 admission may be a marker of severity

Patients with COVID-19 who have high levels of the steroid hormone cortisol on admission to the hospital have a substantially increased risk of dying, according to new study findings.

Researchers assessed 535 patients admitted to major London hospitals. Of these, 403 patients were diagnosed with COVID-19 based on a positive result on real-time polymerase chain reaction testing or a strong clinical and radiological suspicion, despite a negative test. Mean cortisol concentrations in patients with COVID-19 were significantly higher than those not diagnosed with the virus and as of May 8, significantly more patients with COVID-19 died than those without (27.8% vs 6.8%).

Measuring cortisol on admission is potentially “another simple marker to use alongside oxygen saturation levels to help us identify which patients need to be admitted immediately, and which may not,” said Waljit S. Dhillo, MBBS, PhD, head of the division of diabetes, endocrinology and metabolism at Imperial College London.

“Having an early indicator of which patients may deteriorate more quickly will help us with providing the best level of care as quickly as possible. In addition, we can also take cortisol levels into account when we are working out how best to treat our patients,” he said. Read more.

Normal-weight prediabetes patients can benefit from lifestyle changes

Adults of normal weight with prediabetes may derive at least as much benefit from lifestyle health coaching programs as adults who are overweight or obese, results of a recent nonrandomized, real-world study show.

Fasting plasma glucose (FPG) normalized in about 63% of prediabetic adults with normal body mass index (BMI) participating in a personalized coaching program that emphasized exercise, nutrition, and weight management. In contrast, FPG normalized in about 52% of overweight and 44% of obese prediabetic individuals participating in the program.

“It is interesting to note that, although the normal weight group lost the least amount of weight, they still benefited from the lifestyle health coaching program... having a resultant greatest decrease in fasting plasma glucose and normalization to a range of someone without prediabetes,” said researcher Mandy Salmon, MS, a medical student at the University of Pennsylvania, Philadelphia. She presented the findings at the virtual annual scientific sessions of the American Diabetes Association. Read more.

Diabetes-related amputations rise in older adults

The recent resurgence in diabetes-related lower-extremity amputations in the United States is not limited to younger adults, according to the author of a recent study that documents similar increases among an older population of Medicare beneficiaries.

While the rate of amputations fell among these older adults from 2000 to 2009, it increased significantly from 2009 to 2017, albeit at a “less severe rate” than recently reported in younger populations, according to study investigator Jessica Harding, PhD, an assistant professor in the department of surgery at Emory University, Atlanta. Dr. Harding reported the results at the virtual annual scientific sessions of the American Diabetes Association.

The rate of nontraumatic lower extremity amputation (NLEA) was ticking upward by more than 1% per year over the 2009-2017 period. Read more.

For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.

Combining four of five healthy lifestyle choices has been linked to up to a 60% reduced risk for Alzheimer’s dementia in new research that strengthens ties between healthy behaviors and lower dementia risk. “I hope this study will motivate people to engage in a healthy lifestyle by not smoking, being physically and cognitively active, and having a high-quality diet,” lead investigator Klodian Dhana, MD, PhD, department of internal medicine, Rush University Medical Center, Chicago, said in an interview.

The study was published online June 17 in Neurology.
 

Risk-modifying behaviors

To help quantify the impact of a healthy life on risk for Alzheimer’s dementia, Dr. Dhana and colleagues reviewed data from two longitudinal study populations: the Chicago Health and Aging Project (CHAP), with 1,845 participants, and the Memory and Aging Project (MAP), with 920 participants.

They defined a healthy lifestyle score on the basis of the following factors: not smoking; engaging in 150 min/wk or more of physical exercise of moderate to vigorous intensity; light to moderate alcohol consumption (between 1 and less than 15 g/day for women and between 1 and less than 30 g/day for men); consuming a high-quality Mediterranean-DASH Diet Intervention for Neurodegenerative Delay diet (upper 40%); and engaging in late-life cognitive activities (upper 40%). The overall score ranged from 0 to 5.

At baseline, the mean age of participants was 73.2 years in the CHAP study and 81.1 years in the MAP study; 62.4% of the CHAP participants and 75.2% of the MAP participants were women.

During a median follow-up of 5.8 years in CHAP and 6.0 years in MAP, a total of 379 and 229 participants, respectively, developed Alzheimer’s dementia. Rates of dementia decreased with an increasing number of healthy lifestyle behaviors.

In multivariable-adjusted models across the two cohorts, the risk for Alzheimer’s dementia was 27% lower with each additional healthy lifestyle factor (pooled hazard ratio, 0.73; 95% confidence interval, 0.66-0.80).

Compared with individuals with a healthy lifestyle score of 0-1, the risk was 37% lower (pooled HR, 0.63; 95% CI, 0.47-0.84) for those with two or three healthy lifestyle factors and 60% lower (pooled HR, 0.40; 95% CI, 0.28-0.56) for those with four or five healthy lifestyle factors.

“From these findings and the fact that the lifestyle factors we studied are modifiable and in direct control of the individual, it is imperative to promote them concurrently among older adults as a strategy to delay or prevent Alzheimer’s dementia,” Dr. Dhana and colleagues concluded.

In a statement, Dallas Anderson, PhD, program director, division of neuroscience, National Institute on Aging, said the findings help “paint the picture of how multiple factors are likely playing parts in Alzheimer’s disease risk.”

“It’s not a clear cause-and-effect result, but a strong finding because of the dual data sets and combination of modifiable lifestyle factors that appear to lead to risk reduction,” Dr. Anderson added.

Essential questions remain

Commenting on the new study, Luca Giliberto, MD, PhD, neurologist with the Litwin-Zucker Research Center for Alzheimer’s Disease and Memory Disorders at the Feinstein Institutes for Medical Research in Manhasset, N.Y., said this analysis is “further demonstration that a healthy lifestyle is essential to overcome or curb” the risk for Alzheimer’s disease.

“What needs to be determined is how early should we start ‘behaving.’ We should all aim to score four to five factors across our entire lifespan, but this is not always feasible. So, when is the time to behave? Also, what is the relative weight of each of these factors?” said Dr. Giliberto.

Of note, he added, although addressing vascular risk factors such as hypertension, hyperlipidemia, and diabetes “may require an extensive mindful and logistic effort, a healthy diet is effortlessly achieved in some countries, where both the DASH and MIND diets do not need to be ‘prescribed’ but are rather culturally engraved in the population.

“This is, in part, related to the wide availability of high-quality food in these countries, which is not the same in the U.S. This work is one more demonstration of the need to revisit our take on quality of food in the U.S.,” said Dr. Giliberto.

Numerous clinical trials testing lifestyle interventions for dementia prevention are currently underway. The MIND Diet Intervention to Prevent Alzheimer’s Disease, for example, is an interventional clinical trial comparing parallel groups with two different diets. MIND has enrolled more than 600 participants and is ongoing. The anticipated completion date is 2021. Another is the U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER), a multisite randomized clinical trial evaluating whether lifestyle interventions – including exercise, cognitively stimulating activities, and the MIND diet – may protect cognitive function in older adults who are at increased risk for cognitive decline.

Funding for the current study was provided by the National Institutes of Health and the National Institute on Aging. Dr. Dhana and Dr. Giliberto have disclosed no relevant financial relationships.

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

Combining four of five healthy lifestyle choices has been linked to up to a 60% reduced risk for Alzheimer’s dementia in new research that strengthens ties between healthy behaviors and lower dementia risk. “I hope this study will motivate people to engage in a healthy lifestyle by not smoking, being physically and cognitively active, and having a high-quality diet,” lead investigator Klodian Dhana, MD, PhD, department of internal medicine, Rush University Medical Center, Chicago, said in an interview.

The study was published online June 17 in Neurology.
 

Risk-modifying behaviors

To help quantify the impact of a healthy life on risk for Alzheimer’s dementia, Dr. Dhana and colleagues reviewed data from two longitudinal study populations: the Chicago Health and Aging Project (CHAP), with 1,845 participants, and the Memory and Aging Project (MAP), with 920 participants.

They defined a healthy lifestyle score on the basis of the following factors: not smoking; engaging in 150 min/wk or more of physical exercise of moderate to vigorous intensity; light to moderate alcohol consumption (between 1 and less than 15 g/day for women and between 1 and less than 30 g/day for men); consuming a high-quality Mediterranean-DASH Diet Intervention for Neurodegenerative Delay diet (upper 40%); and engaging in late-life cognitive activities (upper 40%). The overall score ranged from 0 to 5.

At baseline, the mean age of participants was 73.2 years in the CHAP study and 81.1 years in the MAP study; 62.4% of the CHAP participants and 75.2% of the MAP participants were women.

During a median follow-up of 5.8 years in CHAP and 6.0 years in MAP, a total of 379 and 229 participants, respectively, developed Alzheimer’s dementia. Rates of dementia decreased with an increasing number of healthy lifestyle behaviors.

In multivariable-adjusted models across the two cohorts, the risk for Alzheimer’s dementia was 27% lower with each additional healthy lifestyle factor (pooled hazard ratio, 0.73; 95% confidence interval, 0.66-0.80).

Compared with individuals with a healthy lifestyle score of 0-1, the risk was 37% lower (pooled HR, 0.63; 95% CI, 0.47-0.84) for those with two or three healthy lifestyle factors and 60% lower (pooled HR, 0.40; 95% CI, 0.28-0.56) for those with four or five healthy lifestyle factors.

“From these findings and the fact that the lifestyle factors we studied are modifiable and in direct control of the individual, it is imperative to promote them concurrently among older adults as a strategy to delay or prevent Alzheimer’s dementia,” Dr. Dhana and colleagues concluded.

In a statement, Dallas Anderson, PhD, program director, division of neuroscience, National Institute on Aging, said the findings help “paint the picture of how multiple factors are likely playing parts in Alzheimer’s disease risk.”

“It’s not a clear cause-and-effect result, but a strong finding because of the dual data sets and combination of modifiable lifestyle factors that appear to lead to risk reduction,” Dr. Anderson added.

Essential questions remain

Commenting on the new study, Luca Giliberto, MD, PhD, neurologist with the Litwin-Zucker Research Center for Alzheimer’s Disease and Memory Disorders at the Feinstein Institutes for Medical Research in Manhasset, N.Y., said this analysis is “further demonstration that a healthy lifestyle is essential to overcome or curb” the risk for Alzheimer’s disease.

“What needs to be determined is how early should we start ‘behaving.’ We should all aim to score four to five factors across our entire lifespan, but this is not always feasible. So, when is the time to behave? Also, what is the relative weight of each of these factors?” said Dr. Giliberto.

Of note, he added, although addressing vascular risk factors such as hypertension, hyperlipidemia, and diabetes “may require an extensive mindful and logistic effort, a healthy diet is effortlessly achieved in some countries, where both the DASH and MIND diets do not need to be ‘prescribed’ but are rather culturally engraved in the population.

“This is, in part, related to the wide availability of high-quality food in these countries, which is not the same in the U.S. This work is one more demonstration of the need to revisit our take on quality of food in the U.S.,” said Dr. Giliberto.

Numerous clinical trials testing lifestyle interventions for dementia prevention are currently underway. The MIND Diet Intervention to Prevent Alzheimer’s Disease, for example, is an interventional clinical trial comparing parallel groups with two different diets. MIND has enrolled more than 600 participants and is ongoing. The anticipated completion date is 2021. Another is the U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER), a multisite randomized clinical trial evaluating whether lifestyle interventions – including exercise, cognitively stimulating activities, and the MIND diet – may protect cognitive function in older adults who are at increased risk for cognitive decline.

Funding for the current study was provided by the National Institutes of Health and the National Institute on Aging. Dr. Dhana and Dr. Giliberto have disclosed no relevant financial relationships.

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

Combining four of five healthy lifestyle choices has been linked to up to a 60% reduced risk for Alzheimer’s dementia in new research that strengthens ties between healthy behaviors and lower dementia risk. “I hope this study will motivate people to engage in a healthy lifestyle by not smoking, being physically and cognitively active, and having a high-quality diet,” lead investigator Klodian Dhana, MD, PhD, department of internal medicine, Rush University Medical Center, Chicago, said in an interview.

The study was published online June 17 in Neurology.
 

Risk-modifying behaviors

To help quantify the impact of a healthy life on risk for Alzheimer’s dementia, Dr. Dhana and colleagues reviewed data from two longitudinal study populations: the Chicago Health and Aging Project (CHAP), with 1,845 participants, and the Memory and Aging Project (MAP), with 920 participants.

They defined a healthy lifestyle score on the basis of the following factors: not smoking; engaging in 150 min/wk or more of physical exercise of moderate to vigorous intensity; light to moderate alcohol consumption (between 1 and less than 15 g/day for women and between 1 and less than 30 g/day for men); consuming a high-quality Mediterranean-DASH Diet Intervention for Neurodegenerative Delay diet (upper 40%); and engaging in late-life cognitive activities (upper 40%). The overall score ranged from 0 to 5.

At baseline, the mean age of participants was 73.2 years in the CHAP study and 81.1 years in the MAP study; 62.4% of the CHAP participants and 75.2% of the MAP participants were women.

During a median follow-up of 5.8 years in CHAP and 6.0 years in MAP, a total of 379 and 229 participants, respectively, developed Alzheimer’s dementia. Rates of dementia decreased with an increasing number of healthy lifestyle behaviors.

In multivariable-adjusted models across the two cohorts, the risk for Alzheimer’s dementia was 27% lower with each additional healthy lifestyle factor (pooled hazard ratio, 0.73; 95% confidence interval, 0.66-0.80).

Compared with individuals with a healthy lifestyle score of 0-1, the risk was 37% lower (pooled HR, 0.63; 95% CI, 0.47-0.84) for those with two or three healthy lifestyle factors and 60% lower (pooled HR, 0.40; 95% CI, 0.28-0.56) for those with four or five healthy lifestyle factors.

“From these findings and the fact that the lifestyle factors we studied are modifiable and in direct control of the individual, it is imperative to promote them concurrently among older adults as a strategy to delay or prevent Alzheimer’s dementia,” Dr. Dhana and colleagues concluded.

In a statement, Dallas Anderson, PhD, program director, division of neuroscience, National Institute on Aging, said the findings help “paint the picture of how multiple factors are likely playing parts in Alzheimer’s disease risk.”

“It’s not a clear cause-and-effect result, but a strong finding because of the dual data sets and combination of modifiable lifestyle factors that appear to lead to risk reduction,” Dr. Anderson added.

Essential questions remain

Commenting on the new study, Luca Giliberto, MD, PhD, neurologist with the Litwin-Zucker Research Center for Alzheimer’s Disease and Memory Disorders at the Feinstein Institutes for Medical Research in Manhasset, N.Y., said this analysis is “further demonstration that a healthy lifestyle is essential to overcome or curb” the risk for Alzheimer’s disease.

“What needs to be determined is how early should we start ‘behaving.’ We should all aim to score four to five factors across our entire lifespan, but this is not always feasible. So, when is the time to behave? Also, what is the relative weight of each of these factors?” said Dr. Giliberto.

Of note, he added, although addressing vascular risk factors such as hypertension, hyperlipidemia, and diabetes “may require an extensive mindful and logistic effort, a healthy diet is effortlessly achieved in some countries, where both the DASH and MIND diets do not need to be ‘prescribed’ but are rather culturally engraved in the population.

“This is, in part, related to the wide availability of high-quality food in these countries, which is not the same in the U.S. This work is one more demonstration of the need to revisit our take on quality of food in the U.S.,” said Dr. Giliberto.

Numerous clinical trials testing lifestyle interventions for dementia prevention are currently underway. The MIND Diet Intervention to Prevent Alzheimer’s Disease, for example, is an interventional clinical trial comparing parallel groups with two different diets. MIND has enrolled more than 600 participants and is ongoing. The anticipated completion date is 2021. Another is the U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER), a multisite randomized clinical trial evaluating whether lifestyle interventions – including exercise, cognitively stimulating activities, and the MIND diet – may protect cognitive function in older adults who are at increased risk for cognitive decline.

Funding for the current study was provided by the National Institutes of Health and the National Institute on Aging. Dr. Dhana and Dr. Giliberto have disclosed no relevant financial relationships.

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

The recent resurgence in diabetes-related lower-extremity amputations in the United States is not limited to younger adults, according to the author of a recent study that documents similar increases among an older population of Medicare beneficiaries.

While the rate of amputations fell among these older adults from 2000 to 2009, it increased significantly from 2009 to 2017, albeit at a “less severe rate” than recently reported in younger populations, said study investigator Jessica Harding, PhD.

The rate of nontraumatic lower extremity amputation (NLEA) was ticking upward by more than 1% per year over the 2009-2017 period, according to Dr. Harding, assistant professor in the department of surgery at Emory University, Atlanta.

This latest report follows one from last year, published in Diabetes Care, that documented an annual percentage increase approaching 6% between 2009 and 2015, driven by larger increases among adults 18-64 years of age, as well as an increase among men.

It’s not clear why rates of NLEA would be on the rise among younger and older adults in the United States, Dr. Harding said, though factors she said could be implicated include changes in amputation practice, increased comorbidities, higher insulin costs, or shortcomings in early prevention programs.

“We need large-scale studies with granular data to tease out key risk factors that could help identify the drivers of these increases in amputations,” Dr. Harding said in a presentation at the virtual annual scientific sessions of the American Diabetes Association.

“In the interim, increased attention to preventive foot care across the age spectrum could benefit adults with diabetes,” she added.

Devastating complication in older adults

The latest findings from Dr. Harding and coauthors emphasize the importance of a “team approach” to early prevention in older adults with diabetes, said Derek LeRoith, MD, PhD, director of research in the division of endocrinology, diabetes, and bone diseases with Icahn School of Medicine at Mount Sinai, New York.

Doug Brunk/MDedge News

“If you take a 75-year-old or even an 80-year-old, their life expectancy can still be a good 10 years or more,” Dr. LeRoith said in an interview. “We shouldn’t give up on them – we should be treating them to prevent complications.”

Lower-extremity amputation is a “particularly devastating” complication that can compromise mobility, ability to exercise, and motivation, according to Dr. LeRoith, lead author of a recent Endocrine Society clinical practice guideline that urges referral of older adults with diabetes to a podiatrist, orthopedist, or vascular specialist for preventive care.

“Quite often, treating their glucose or high blood pressure will be much more difficult because of these changes,” he said.
 

Lower extremity amputation trends upward

Rates of NLEA declined for years, only to rebound by 50%, according to authors of a recent analysis of Nationwide Inpatient Sample (NIS) data reported last year. In their report, the age-standardized diabetes-related NLEA rate per 1,000 adults with diabetes went from 5.30 in 2000, down to 3.07 in 2009/2010, and back up to 4.62 by 2015 (Diabetes Care. 2019 Jan;42:50-4).

The resurgence was fueled mainly by an increased rate of amputations in younger and middle-aged adults and men, and through increases in minor amputations, notably the toe, according to the investigators. “These changes in trend are concerning because of the disabling and costly consequences of NLEAs as well as what they may mean for the direction of efforts to reduce diabetes-related complications,” authors of that report said at the time.

In the current study, Dr. Harding and colleagues included Medicare Parts A and B claims data for beneficiaries enrolled from 2000 to 2017. There were 4.6 million Medicare fee-for-service beneficiaries with diabetes in 2000, increasing to 6.9 million in 2017, she reported at the virtual ADA meeting.

Rates of NLEA followed a trajectory similar to what was seen in the earlier NIS report, falling from 8.5 per 1,000 persons in 2000 to 4.4 in 2009, for an annual percentage change of –7.9 (P < .001), Dr. Harding said. Then rates ticked upward again, to 4.8 in 2017, for an annual percentage change of 1.2 over that later period (P < .001).

While the trend was similar for most subgroups analyzed, the absolute rates were highest among men and black individuals in this older patient population, reported Dr. Harding and coauthors.

Dr. Harding said she and coauthors had no disclosures related to the research, which was performed as a collaboration between Emory University and the Centers for Disease Control and Prevention Division of Diabetes Translation.

SOURCE: Harding J. ADA 2020, Abstract 106-OR.

The recent resurgence in diabetes-related lower-extremity amputations in the United States is not limited to younger adults, according to the author of a recent study that documents similar increases among an older population of Medicare beneficiaries.

While the rate of amputations fell among these older adults from 2000 to 2009, it increased significantly from 2009 to 2017, albeit at a “less severe rate” than recently reported in younger populations, said study investigator Jessica Harding, PhD.

The rate of nontraumatic lower extremity amputation (NLEA) was ticking upward by more than 1% per year over the 2009-2017 period, according to Dr. Harding, assistant professor in the department of surgery at Emory University, Atlanta.

This latest report follows one from last year, published in Diabetes Care, that documented an annual percentage increase approaching 6% between 2009 and 2015, driven by larger increases among adults 18-64 years of age, as well as an increase among men.

It’s not clear why rates of NLEA would be on the rise among younger and older adults in the United States, Dr. Harding said, though factors she said could be implicated include changes in amputation practice, increased comorbidities, higher insulin costs, or shortcomings in early prevention programs.

“We need large-scale studies with granular data to tease out key risk factors that could help identify the drivers of these increases in amputations,” Dr. Harding said in a presentation at the virtual annual scientific sessions of the American Diabetes Association.

“In the interim, increased attention to preventive foot care across the age spectrum could benefit adults with diabetes,” she added.

Devastating complication in older adults

The latest findings from Dr. Harding and coauthors emphasize the importance of a “team approach” to early prevention in older adults with diabetes, said Derek LeRoith, MD, PhD, director of research in the division of endocrinology, diabetes, and bone diseases with Icahn School of Medicine at Mount Sinai, New York.

Doug Brunk/MDedge News

“If you take a 75-year-old or even an 80-year-old, their life expectancy can still be a good 10 years or more,” Dr. LeRoith said in an interview. “We shouldn’t give up on them – we should be treating them to prevent complications.”

Lower-extremity amputation is a “particularly devastating” complication that can compromise mobility, ability to exercise, and motivation, according to Dr. LeRoith, lead author of a recent Endocrine Society clinical practice guideline that urges referral of older adults with diabetes to a podiatrist, orthopedist, or vascular specialist for preventive care.

“Quite often, treating their glucose or high blood pressure will be much more difficult because of these changes,” he said.
 

Lower extremity amputation trends upward

Rates of NLEA declined for years, only to rebound by 50%, according to authors of a recent analysis of Nationwide Inpatient Sample (NIS) data reported last year. In their report, the age-standardized diabetes-related NLEA rate per 1,000 adults with diabetes went from 5.30 in 2000, down to 3.07 in 2009/2010, and back up to 4.62 by 2015 (Diabetes Care. 2019 Jan;42:50-4).

The resurgence was fueled mainly by an increased rate of amputations in younger and middle-aged adults and men, and through increases in minor amputations, notably the toe, according to the investigators. “These changes in trend are concerning because of the disabling and costly consequences of NLEAs as well as what they may mean for the direction of efforts to reduce diabetes-related complications,” authors of that report said at the time.

In the current study, Dr. Harding and colleagues included Medicare Parts A and B claims data for beneficiaries enrolled from 2000 to 2017. There were 4.6 million Medicare fee-for-service beneficiaries with diabetes in 2000, increasing to 6.9 million in 2017, she reported at the virtual ADA meeting.

Rates of NLEA followed a trajectory similar to what was seen in the earlier NIS report, falling from 8.5 per 1,000 persons in 2000 to 4.4 in 2009, for an annual percentage change of –7.9 (P < .001), Dr. Harding said. Then rates ticked upward again, to 4.8 in 2017, for an annual percentage change of 1.2 over that later period (P < .001).

While the trend was similar for most subgroups analyzed, the absolute rates were highest among men and black individuals in this older patient population, reported Dr. Harding and coauthors.

Dr. Harding said she and coauthors had no disclosures related to the research, which was performed as a collaboration between Emory University and the Centers for Disease Control and Prevention Division of Diabetes Translation.

SOURCE: Harding J. ADA 2020, Abstract 106-OR.

The recent resurgence in diabetes-related lower-extremity amputations in the United States is not limited to younger adults, according to the author of a recent study that documents similar increases among an older population of Medicare beneficiaries.

While the rate of amputations fell among these older adults from 2000 to 2009, it increased significantly from 2009 to 2017, albeit at a “less severe rate” than recently reported in younger populations, said study investigator Jessica Harding, PhD.

The rate of nontraumatic lower extremity amputation (NLEA) was ticking upward by more than 1% per year over the 2009-2017 period, according to Dr. Harding, assistant professor in the department of surgery at Emory University, Atlanta.

This latest report follows one from last year, published in Diabetes Care, that documented an annual percentage increase approaching 6% between 2009 and 2015, driven by larger increases among adults 18-64 years of age, as well as an increase among men.

It’s not clear why rates of NLEA would be on the rise among younger and older adults in the United States, Dr. Harding said, though factors she said could be implicated include changes in amputation practice, increased comorbidities, higher insulin costs, or shortcomings in early prevention programs.

“We need large-scale studies with granular data to tease out key risk factors that could help identify the drivers of these increases in amputations,” Dr. Harding said in a presentation at the virtual annual scientific sessions of the American Diabetes Association.

“In the interim, increased attention to preventive foot care across the age spectrum could benefit adults with diabetes,” she added.

Devastating complication in older adults

The latest findings from Dr. Harding and coauthors emphasize the importance of a “team approach” to early prevention in older adults with diabetes, said Derek LeRoith, MD, PhD, director of research in the division of endocrinology, diabetes, and bone diseases with Icahn School of Medicine at Mount Sinai, New York.

Doug Brunk/MDedge News

“If you take a 75-year-old or even an 80-year-old, their life expectancy can still be a good 10 years or more,” Dr. LeRoith said in an interview. “We shouldn’t give up on them – we should be treating them to prevent complications.”

Lower-extremity amputation is a “particularly devastating” complication that can compromise mobility, ability to exercise, and motivation, according to Dr. LeRoith, lead author of a recent Endocrine Society clinical practice guideline that urges referral of older adults with diabetes to a podiatrist, orthopedist, or vascular specialist for preventive care.

“Quite often, treating their glucose or high blood pressure will be much more difficult because of these changes,” he said.
 

Lower extremity amputation trends upward

Rates of NLEA declined for years, only to rebound by 50%, according to authors of a recent analysis of Nationwide Inpatient Sample (NIS) data reported last year. In their report, the age-standardized diabetes-related NLEA rate per 1,000 adults with diabetes went from 5.30 in 2000, down to 3.07 in 2009/2010, and back up to 4.62 by 2015 (Diabetes Care. 2019 Jan;42:50-4).

The resurgence was fueled mainly by an increased rate of amputations in younger and middle-aged adults and men, and through increases in minor amputations, notably the toe, according to the investigators. “These changes in trend are concerning because of the disabling and costly consequences of NLEAs as well as what they may mean for the direction of efforts to reduce diabetes-related complications,” authors of that report said at the time.

In the current study, Dr. Harding and colleagues included Medicare Parts A and B claims data for beneficiaries enrolled from 2000 to 2017. There were 4.6 million Medicare fee-for-service beneficiaries with diabetes in 2000, increasing to 6.9 million in 2017, she reported at the virtual ADA meeting.

Rates of NLEA followed a trajectory similar to what was seen in the earlier NIS report, falling from 8.5 per 1,000 persons in 2000 to 4.4 in 2009, for an annual percentage change of –7.9 (P < .001), Dr. Harding said. Then rates ticked upward again, to 4.8 in 2017, for an annual percentage change of 1.2 over that later period (P < .001).

While the trend was similar for most subgroups analyzed, the absolute rates were highest among men and black individuals in this older patient population, reported Dr. Harding and coauthors.

Dr. Harding said she and coauthors had no disclosures related to the research, which was performed as a collaboration between Emory University and the Centers for Disease Control and Prevention Division of Diabetes Translation.

SOURCE: Harding J. ADA 2020, Abstract 106-OR.

As we reopen our offices we are faced with the challenge of determining the best way to do it safely – protecting ourselves, our staff, and our patients. The Infectious Diseases Society of America recently issued an evidence-based guideline to help clinicians in developing a sound approach to this issue, and this guideline, along with recommendations from the Centers for Disease Control and Prevention, should allow us to move ahead safely.

In this column we will focus on selected details of the recommendations from IDSA and the CDC that may be helpful in primary care offices.
 

Face masks

Many clinicians have asked whether a physician should use a mask while seeing patients without COVID-19 in the office, and if yes, which type. The IDSA guideline states that mask usage is imperative for reducing the risk of health care workers contracting COVID-19.¹ The evidence is derived from a number of sources, including a retrospective study from Wuhan (China) University that examined two groups of health care workers during the outbreak. The first group wore N95 masks and washed their hands frequently, while the second group did not wear masks and washed their hands less frequently. In the group that took greater actions to protect themselves, none of the 493 staff members contracted COVID-19, compared with 10 of 213 staff members in the other group. The decrease in infection rate occurred in the group that wore masks despite the fact that this group had 733% more exposure to COVID-19 patients.² Further evidence came from a case-control study done in hospitals in Hong Kong during the 2003 SARS-CoV outbreak.³ This study showed that mask wearing was the most significant intervention for reducing infection, followed by gowning, and then handwashing. These findings make it clear that mask usage is a must for all health care providers who may be caring for patients who could have COVID-19.

The guideline also reviews evidence about the use of surgical masks versus N95 masks. On reviewing indirect evidence from the SARS-CoV epidemic, IDSA found that wearing any mask – surgical or N95 – led to a large reduction in the risk of developing an infection. In this systematic review of five observational studies in health care personnel, for those wearing surgical masks, the odds ratio for developing an infection was 0.13 (95% CI, 0.03-0.62), and for those wearing N95 masks, the odds ratio was 0.12 (95% CI, 0.06-0.26). There was not a significant difference between risk reductions for those who wore surgical masks and N95 masks, respectively.^1,4 The IDSA guideline panel recommended “that health care personnel caring for patients with suspected or known COVID-19 use either a surgical mask or N95 respirator ... as part of appropriate PPE.” Since there is not a significant difference in outcomes between those who use surgical masks and those who use N95 respirators, and the IDSA guideline states either type of mask is considered appropriate when taking care of patients with suspected or known COVID-19, in our opinion, use of surgical masks rather than N95s is sufficient when performing low-risk activities. Such activities include seeing patients who do not have a high likelihood of COVID-19 in the office setting.

The IDSA recommendation also discusses universal masking, defined as both patients and clinicians wearing masks. The recommendation is supported by the findings of a study in which universal mask usage was used to prevent the spread of H1N 1 during the 2009 outbreak. In this study of staff members and patients exposed to H1N1 who all wore masks, only 0.48% of 836 acquired infection. In the same study, not wearing a mask by either the provider or patient increased the risk of infection.⁵ Also, in a prospective study of hematopoietic stem cell transplant patients, universal masking caused infection rates to drop from 10.3% to 4.4%.⁶

The IDSA guideline states the following: “There may be some, albeit uncertain, benefit to universal masking in the absence of resource constraints. However, the benefits of universal masking with surgical masks should be weighed against the risk of increasing the PPE burn rate and contextualized to the background COVID-19 prevalence rate for asymptomatic or minimally symptomatic HCPs [health care providers] and visitors.”¹

The CDC’s guidance statement says the following: “Continued community transmission has increased the number of individuals potentially exposed to and infectious with SARS-CoV-2. Fever and symptom screening have proven to be relatively ineffective in identifying all infected individuals, including HCPs. Symptom screening also will not identify individuals who are infected but otherwise asymptomatic or pre-symptomatic; additional interventions are needed to limit the unrecognized introduction of SARS-CoV-2 into healthcare settings by these individuals. As part of aggressive source control measures, healthcare facilities should consider implementing policies requiring everyone entering the facility to wear a cloth face covering (if tolerated) while in the building, regardless of symptoms.”⁷

It is our opinion, based on the CDC and IDSA recommendations, that both clinicians and patients should be required to wear masks when patients are seen in the office if possible. Many offices have instituted a policy that says, if a patient refuses to wear a mask during an office visit, then the patient will not be seen.
 

Eye protection

Many clinicians are uncertain about whether eye protection needs to be used when seeing asymptomatic patients. The IDSA acknowledges that there are not studies that have looked critically at eye protection, but the society also acknowledges “appropriate personal protective equipment includes, in addition to a mask or respirator, eye protection, gown and gloves.”¹ In addition, the CDC recommends that, for healthcare workers located in areas with moderate or higher prevalence of COVID-19, HCPs should wear eye protection in addition to facemasks since they may encounter asymptomatic individuals with COVID-19.

Gowns and gloves

Gowns and gloves are recommended as a part of personal protective gear when caring for patients who have COVID-19. The IDSA guideline is clear in its recommendations, but does not cite evidence for having no gloves versus having gloves. Furthermore, they state that the evidence is insufficient to recommend double gloves, with the top glove used to take off a personal protective gown, and the inner glove discarded after the gown is removed. The CDC do not make recommendations for routine use of gloves in the care of patients who do not have COVID-19, even in areas where there may be asymptomatic COVID-19, and recommends standard precautions, specifically practicing hand hygiene before and after patient contact.⁸
 

The Bottom Line

When seeing patients with COVID-19, N-95 masks, goggles or face shields, gowns, and gloves should be used, with hand hygiene routinely practiced before and after seeing patients. For offices seeing patients not suspected of having COVID-19, the IDSA guideline clarifies that there is not a statistical difference in acquisition of infection with the use of surgical face masks vs N95 respirators. According to the CDC recommendations, eye protection in addition to facemasks should be used by the health care provider, and masks should be worn by patients. Hand hygiene should be used routinely before and after all patient contact. With use of these approaches, it should be safe for offices to reopen and see patients.
 

Neil Skolnik, MD, is professor of family and community medicine at the Thomas Jefferson University, Philadelphia, and associate director of the Family Medicine Residency Program at Abington (Pa.) Jefferson Health. Jeffrey Matthews, DO, is a second-year resident in the Family Medicine Residency at Abington Jefferson Health. For questions or comments, feel free to contact Dr. Skolnik on Twitter @NeilSkolnik.

References

1. Lynch JB, Davitkov P, Anderson DJ, et al. COVID-19 Guideline, Part 2: Infection Prevention. IDSA Home. https://www.idsociety.org/practice-guideline/covid-19-guideline-infection-prevention/. April 27, 2020. Accessed June 10, 2020.

2. J Hosp Infect. 2020 May;105(1):104-5.

3. Lancet. 2003;361(9368):1519-20.

4. Influenza Other Respir Viruses. 2020 Apr 4. doi: 2020;10.1111/irv.12745.

5. J Hosp Infect. 2010;74(3):271-7.

6. Clin Infect Dis. 2016;63(8):999-1006.

7. Centers for Disease Control and Prevention. Interim Infection Prevention and Control Recommendations for Patients with Suspected or Confirmed Coronavirus Disease 2019 (COVID-19) in Healthcare Settings. https://www.cdc.gov/coronavirus/2019-ncov/hcp/infection-control-recommendations.html. Accessed Jun 16, 2020.

8. Centers for Disease Control and Prevention. Healthcare Infection Prevention and Control FAQs for COVID-19. https://www.cdc.gov/coronavirus/2019-ncov/hcp/infection-control-faq.html. Accessed June 15, 2020.
 

As we reopen our offices we are faced with the challenge of determining the best way to do it safely – protecting ourselves, our staff, and our patients. The Infectious Diseases Society of America recently issued an evidence-based guideline to help clinicians in developing a sound approach to this issue, and this guideline, along with recommendations from the Centers for Disease Control and Prevention, should allow us to move ahead safely.

In this column we will focus on selected details of the recommendations from IDSA and the CDC that may be helpful in primary care offices.
 

Face masks

Many clinicians have asked whether a physician should use a mask while seeing patients without COVID-19 in the office, and if yes, which type. The IDSA guideline states that mask usage is imperative for reducing the risk of health care workers contracting COVID-19.¹ The evidence is derived from a number of sources, including a retrospective study from Wuhan (China) University that examined two groups of health care workers during the outbreak. The first group wore N95 masks and washed their hands frequently, while the second group did not wear masks and washed their hands less frequently. In the group that took greater actions to protect themselves, none of the 493 staff members contracted COVID-19, compared with 10 of 213 staff members in the other group. The decrease in infection rate occurred in the group that wore masks despite the fact that this group had 733% more exposure to COVID-19 patients.² Further evidence came from a case-control study done in hospitals in Hong Kong during the 2003 SARS-CoV outbreak.³ This study showed that mask wearing was the most significant intervention for reducing infection, followed by gowning, and then handwashing. These findings make it clear that mask usage is a must for all health care providers who may be caring for patients who could have COVID-19.

The guideline also reviews evidence about the use of surgical masks versus N95 masks. On reviewing indirect evidence from the SARS-CoV epidemic, IDSA found that wearing any mask – surgical or N95 – led to a large reduction in the risk of developing an infection. In this systematic review of five observational studies in health care personnel, for those wearing surgical masks, the odds ratio for developing an infection was 0.13 (95% CI, 0.03-0.62), and for those wearing N95 masks, the odds ratio was 0.12 (95% CI, 0.06-0.26). There was not a significant difference between risk reductions for those who wore surgical masks and N95 masks, respectively.^1,4 The IDSA guideline panel recommended “that health care personnel caring for patients with suspected or known COVID-19 use either a surgical mask or N95 respirator ... as part of appropriate PPE.” Since there is not a significant difference in outcomes between those who use surgical masks and those who use N95 respirators, and the IDSA guideline states either type of mask is considered appropriate when taking care of patients with suspected or known COVID-19, in our opinion, use of surgical masks rather than N95s is sufficient when performing low-risk activities. Such activities include seeing patients who do not have a high likelihood of COVID-19 in the office setting.

The IDSA recommendation also discusses universal masking, defined as both patients and clinicians wearing masks. The recommendation is supported by the findings of a study in which universal mask usage was used to prevent the spread of H1N 1 during the 2009 outbreak. In this study of staff members and patients exposed to H1N1 who all wore masks, only 0.48% of 836 acquired infection. In the same study, not wearing a mask by either the provider or patient increased the risk of infection.⁵ Also, in a prospective study of hematopoietic stem cell transplant patients, universal masking caused infection rates to drop from 10.3% to 4.4%.⁶

The IDSA guideline states the following: “There may be some, albeit uncertain, benefit to universal masking in the absence of resource constraints. However, the benefits of universal masking with surgical masks should be weighed against the risk of increasing the PPE burn rate and contextualized to the background COVID-19 prevalence rate for asymptomatic or minimally symptomatic HCPs [health care providers] and visitors.”¹

The CDC’s guidance statement says the following: “Continued community transmission has increased the number of individuals potentially exposed to and infectious with SARS-CoV-2. Fever and symptom screening have proven to be relatively ineffective in identifying all infected individuals, including HCPs. Symptom screening also will not identify individuals who are infected but otherwise asymptomatic or pre-symptomatic; additional interventions are needed to limit the unrecognized introduction of SARS-CoV-2 into healthcare settings by these individuals. As part of aggressive source control measures, healthcare facilities should consider implementing policies requiring everyone entering the facility to wear a cloth face covering (if tolerated) while in the building, regardless of symptoms.”⁷

It is our opinion, based on the CDC and IDSA recommendations, that both clinicians and patients should be required to wear masks when patients are seen in the office if possible. Many offices have instituted a policy that says, if a patient refuses to wear a mask during an office visit, then the patient will not be seen.
 

Eye protection

Many clinicians are uncertain about whether eye protection needs to be used when seeing asymptomatic patients. The IDSA acknowledges that there are not studies that have looked critically at eye protection, but the society also acknowledges “appropriate personal protective equipment includes, in addition to a mask or respirator, eye protection, gown and gloves.”¹ In addition, the CDC recommends that, for healthcare workers located in areas with moderate or higher prevalence of COVID-19, HCPs should wear eye protection in addition to facemasks since they may encounter asymptomatic individuals with COVID-19.

Gowns and gloves

Gowns and gloves are recommended as a part of personal protective gear when caring for patients who have COVID-19. The IDSA guideline is clear in its recommendations, but does not cite evidence for having no gloves versus having gloves. Furthermore, they state that the evidence is insufficient to recommend double gloves, with the top glove used to take off a personal protective gown, and the inner glove discarded after the gown is removed. The CDC do not make recommendations for routine use of gloves in the care of patients who do not have COVID-19, even in areas where there may be asymptomatic COVID-19, and recommends standard precautions, specifically practicing hand hygiene before and after patient contact.⁸
 

The Bottom Line

When seeing patients with COVID-19, N-95 masks, goggles or face shields, gowns, and gloves should be used, with hand hygiene routinely practiced before and after seeing patients. For offices seeing patients not suspected of having COVID-19, the IDSA guideline clarifies that there is not a statistical difference in acquisition of infection with the use of surgical face masks vs N95 respirators. According to the CDC recommendations, eye protection in addition to facemasks should be used by the health care provider, and masks should be worn by patients. Hand hygiene should be used routinely before and after all patient contact. With use of these approaches, it should be safe for offices to reopen and see patients.
 

Neil Skolnik, MD, is professor of family and community medicine at the Thomas Jefferson University, Philadelphia, and associate director of the Family Medicine Residency Program at Abington (Pa.) Jefferson Health. Jeffrey Matthews, DO, is a second-year resident in the Family Medicine Residency at Abington Jefferson Health. For questions or comments, feel free to contact Dr. Skolnik on Twitter @NeilSkolnik.

References

1. Lynch JB, Davitkov P, Anderson DJ, et al. COVID-19 Guideline, Part 2: Infection Prevention. IDSA Home. https://www.idsociety.org/practice-guideline/covid-19-guideline-infection-prevention/. April 27, 2020. Accessed June 10, 2020.

2. J Hosp Infect. 2020 May;105(1):104-5.

3. Lancet. 2003;361(9368):1519-20.

4. Influenza Other Respir Viruses. 2020 Apr 4. doi: 2020;10.1111/irv.12745.

5. J Hosp Infect. 2010;74(3):271-7.

6. Clin Infect Dis. 2016;63(8):999-1006.

7. Centers for Disease Control and Prevention. Interim Infection Prevention and Control Recommendations for Patients with Suspected or Confirmed Coronavirus Disease 2019 (COVID-19) in Healthcare Settings. https://www.cdc.gov/coronavirus/2019-ncov/hcp/infection-control-recommendations.html. Accessed Jun 16, 2020.

8. Centers for Disease Control and Prevention. Healthcare Infection Prevention and Control FAQs for COVID-19. https://www.cdc.gov/coronavirus/2019-ncov/hcp/infection-control-faq.html. Accessed June 15, 2020.
 

As we reopen our offices we are faced with the challenge of determining the best way to do it safely – protecting ourselves, our staff, and our patients. The Infectious Diseases Society of America recently issued an evidence-based guideline to help clinicians in developing a sound approach to this issue, and this guideline, along with recommendations from the Centers for Disease Control and Prevention, should allow us to move ahead safely.

In this column we will focus on selected details of the recommendations from IDSA and the CDC that may be helpful in primary care offices.
 

Face masks

Many clinicians have asked whether a physician should use a mask while seeing patients without COVID-19 in the office, and if yes, which type. The IDSA guideline states that mask usage is imperative for reducing the risk of health care workers contracting COVID-19.¹ The evidence is derived from a number of sources, including a retrospective study from Wuhan (China) University that examined two groups of health care workers during the outbreak. The first group wore N95 masks and washed their hands frequently, while the second group did not wear masks and washed their hands less frequently. In the group that took greater actions to protect themselves, none of the 493 staff members contracted COVID-19, compared with 10 of 213 staff members in the other group. The decrease in infection rate occurred in the group that wore masks despite the fact that this group had 733% more exposure to COVID-19 patients.² Further evidence came from a case-control study done in hospitals in Hong Kong during the 2003 SARS-CoV outbreak.³ This study showed that mask wearing was the most significant intervention for reducing infection, followed by gowning, and then handwashing. These findings make it clear that mask usage is a must for all health care providers who may be caring for patients who could have COVID-19.

The guideline also reviews evidence about the use of surgical masks versus N95 masks. On reviewing indirect evidence from the SARS-CoV epidemic, IDSA found that wearing any mask – surgical or N95 – led to a large reduction in the risk of developing an infection. In this systematic review of five observational studies in health care personnel, for those wearing surgical masks, the odds ratio for developing an infection was 0.13 (95% CI, 0.03-0.62), and for those wearing N95 masks, the odds ratio was 0.12 (95% CI, 0.06-0.26). There was not a significant difference between risk reductions for those who wore surgical masks and N95 masks, respectively.^1,4 The IDSA guideline panel recommended “that health care personnel caring for patients with suspected or known COVID-19 use either a surgical mask or N95 respirator ... as part of appropriate PPE.” Since there is not a significant difference in outcomes between those who use surgical masks and those who use N95 respirators, and the IDSA guideline states either type of mask is considered appropriate when taking care of patients with suspected or known COVID-19, in our opinion, use of surgical masks rather than N95s is sufficient when performing low-risk activities. Such activities include seeing patients who do not have a high likelihood of COVID-19 in the office setting.

The IDSA recommendation also discusses universal masking, defined as both patients and clinicians wearing masks. The recommendation is supported by the findings of a study in which universal mask usage was used to prevent the spread of H1N 1 during the 2009 outbreak. In this study of staff members and patients exposed to H1N1 who all wore masks, only 0.48% of 836 acquired infection. In the same study, not wearing a mask by either the provider or patient increased the risk of infection.⁵ Also, in a prospective study of hematopoietic stem cell transplant patients, universal masking caused infection rates to drop from 10.3% to 4.4%.⁶

The IDSA guideline states the following: “There may be some, albeit uncertain, benefit to universal masking in the absence of resource constraints. However, the benefits of universal masking with surgical masks should be weighed against the risk of increasing the PPE burn rate and contextualized to the background COVID-19 prevalence rate for asymptomatic or minimally symptomatic HCPs [health care providers] and visitors.”¹

The CDC’s guidance statement says the following: “Continued community transmission has increased the number of individuals potentially exposed to and infectious with SARS-CoV-2. Fever and symptom screening have proven to be relatively ineffective in identifying all infected individuals, including HCPs. Symptom screening also will not identify individuals who are infected but otherwise asymptomatic or pre-symptomatic; additional interventions are needed to limit the unrecognized introduction of SARS-CoV-2 into healthcare settings by these individuals. As part of aggressive source control measures, healthcare facilities should consider implementing policies requiring everyone entering the facility to wear a cloth face covering (if tolerated) while in the building, regardless of symptoms.”⁷

It is our opinion, based on the CDC and IDSA recommendations, that both clinicians and patients should be required to wear masks when patients are seen in the office if possible. Many offices have instituted a policy that says, if a patient refuses to wear a mask during an office visit, then the patient will not be seen.
 

Eye protection

Many clinicians are uncertain about whether eye protection needs to be used when seeing asymptomatic patients. The IDSA acknowledges that there are not studies that have looked critically at eye protection, but the society also acknowledges “appropriate personal protective equipment includes, in addition to a mask or respirator, eye protection, gown and gloves.”¹ In addition, the CDC recommends that, for healthcare workers located in areas with moderate or higher prevalence of COVID-19, HCPs should wear eye protection in addition to facemasks since they may encounter asymptomatic individuals with COVID-19.

Gowns and gloves

Gowns and gloves are recommended as a part of personal protective gear when caring for patients who have COVID-19. The IDSA guideline is clear in its recommendations, but does not cite evidence for having no gloves versus having gloves. Furthermore, they state that the evidence is insufficient to recommend double gloves, with the top glove used to take off a personal protective gown, and the inner glove discarded after the gown is removed. The CDC do not make recommendations for routine use of gloves in the care of patients who do not have COVID-19, even in areas where there may be asymptomatic COVID-19, and recommends standard precautions, specifically practicing hand hygiene before and after patient contact.⁸
 

The Bottom Line

When seeing patients with COVID-19, N-95 masks, goggles or face shields, gowns, and gloves should be used, with hand hygiene routinely practiced before and after seeing patients. For offices seeing patients not suspected of having COVID-19, the IDSA guideline clarifies that there is not a statistical difference in acquisition of infection with the use of surgical face masks vs N95 respirators. According to the CDC recommendations, eye protection in addition to facemasks should be used by the health care provider, and masks should be worn by patients. Hand hygiene should be used routinely before and after all patient contact. With use of these approaches, it should be safe for offices to reopen and see patients.
 

Neil Skolnik, MD, is professor of family and community medicine at the Thomas Jefferson University, Philadelphia, and associate director of the Family Medicine Residency Program at Abington (Pa.) Jefferson Health. Jeffrey Matthews, DO, is a second-year resident in the Family Medicine Residency at Abington Jefferson Health. For questions or comments, feel free to contact Dr. Skolnik on Twitter @NeilSkolnik.

References

1. Lynch JB, Davitkov P, Anderson DJ, et al. COVID-19 Guideline, Part 2: Infection Prevention. IDSA Home. https://www.idsociety.org/practice-guideline/covid-19-guideline-infection-prevention/. April 27, 2020. Accessed June 10, 2020.

2. J Hosp Infect. 2020 May;105(1):104-5.

3. Lancet. 2003;361(9368):1519-20.

4. Influenza Other Respir Viruses. 2020 Apr 4. doi: 2020;10.1111/irv.12745.

5. J Hosp Infect. 2010;74(3):271-7.

6. Clin Infect Dis. 2016;63(8):999-1006.

7. Centers for Disease Control and Prevention. Interim Infection Prevention and Control Recommendations for Patients with Suspected or Confirmed Coronavirus Disease 2019 (COVID-19) in Healthcare Settings. https://www.cdc.gov/coronavirus/2019-ncov/hcp/infection-control-recommendations.html. Accessed Jun 16, 2020.

8. Centers for Disease Control and Prevention. Healthcare Infection Prevention and Control FAQs for COVID-19. https://www.cdc.gov/coronavirus/2019-ncov/hcp/infection-control-faq.html. Accessed June 15, 2020.
 

Selective serotonin reuptake inhibitors (SSRIs) are associated with an increased risk of committing a violent crime, an effect that may linger up to 12 weeks after treatment discontinuation, new research suggests. However, investigators say the finding should be interpreted with caution.

A large population-based study of more than 800,000 individuals showed those taking these antidepressants had an overall 2.7% increased risk of committing a violent crime while on the medications compared with when they were not taking them.

The increased risk persisted up to 12 weeks after discontinuing SSRIs and then returned to pretreatment levels. The risk was highest in younger individuals and those with a history of a prior violent crime.

“Our findings should be interpreted with caution [because] we do not know how far the association between SSRI medication and violent crime reflect causation,” lead author Tyra Lagerberg, MSc, a PhD candidate at Karolinska Institute, Sweden, said in an interview.

“Our findings should not be used as grounds for individuals to go off their [SSRI] medication or for clinicians to withhold medication from those who might benefit from it,” Ms. Lagerberg said.

The study was published online May 29 in European Neuropsychopharmacology.
 

Previous concerns

There has been “apprehension” about a possible association between SSRIs and elevated risk of aggression and violence, especially in young people, but it “remains unclear” if there is a similar risk in middle-aged and older adults, the authors noted. Moreover, it is unclear whether the risk of violence varies with time after initiating and discontinuing SSRI treatment.

To assess how the risk of violent crime might vary by age and time after SSRI treatment initiation and discontinuation, the researchers calculated absolute rates of violent crime per 1000 person-years during on- and off-treatment periods and also conducted within-group analyses.

The cohort, which was derived from several Swedish national registers, included all individuals in Sweden prescribed an SSRI between Jan. 1, 2006, and Dec. 31, 2013 (n = 785,337, 64.2% female) over an average follow-up of 7.3 years.

Some of the covariates used in the analyses included age, recent or previous violent crime, use of non-SSRI medications, sex, family income, education, county of residence, birth country, and lifetime diagnoses.
 

“Rare” effect

Almost the entire study cohort (99%) changed their SSRI treatment over the follow-up period. During this time, of the full study cohort, 2.7% committed violent crimes (21,203 crimes in 5,707,293 person-years).

More men than women were convicted of a violent crime (5.7% vs 1.0%, respectively).

Absolute rates of violent crime were lower in treated versus nontreated periods across all age categories (other than those between 15 and 24 years) when covariates were not taken into account.

However, when hazards during the on- and off-treatment periods were compared and adjusted for covariables, SSRI treatment was associated with a “modest increased” risk of violent crime (HR, 1.10) – particularly in those ages 15-25 years and ages 25–34 years (HR, 1.19 and 1.16, respectively).

Moreover, further analysis stratifying the cohort according to previous violent crime revealed that the elevated risk for violent crime convictions “seemed to be confined to the individuals with previous criminality,” compared to those with no criminal history (HR, 1.13 vs. 1.07).

The within-individual analysis included 2.6% of the overall cohort who experienced SSRI treatment switching as well as ≥1 violent event.

These individuals differed from the overall cohort in that they tended to be younger (close to half were aged 15-24 years compared with one quarter in the overall cohort) and predominantly male (77% vs. 36%, respectively).

When the hazard of violent crime was compared between individuals’ periods on and off medication, there was a significantly increased hazard during treatment in the whole cohort (HR, 1.26), but in particular, in those aged 25-34 years and 35-44 years (HR, 1.35 and 1.15, respectively).

The within-individual HRs remained elevated for up to 12 weeks post discontinuation of the SSRI (HR, 1.37 during the first 28 days; HR, 1.20 during days 29-84). Although women had a significantly elevated on-treatment hazard in the youngest age category, they had a lower incidence of crime across ages.

Treatment with benzodiazepines was associated with a significantly higher hazard of violent crime and treatment with non-SSRI antidepressants was associated with a “modest but nonsignificantly elevated” hazard.

By contrast, treatment with other psychotropic drugs was not associated with elevated risk.
 

Warn patients

Commenting on the study, Eduard Vieta, MD, PhD, professor of psychiatry, Institute of Neuroscience, University of Barcelona, Spain, and author of an accompanying editorial, said it’s still not known if the mediating factor in the increased risk of violent crime was the SSRI or the underlying mental condition that prompted the prescription.

Dr. Vieta, who was not involved with the study, added that the results “raise a note of caution in terms of making a very accurate diagnosis and treatment in patients with a history of conviction, violence, or criminality, and opting ideally for psychosocial therapies whenever possible in this population.”

Also commenting on the study, Michael Thase, MD, professor of psychiatry, University of Pennsylvania, Philadelphia, said the findings are “not easy to brush away or explain away.”

Dr. Thase, who was not involved with the study, continued, “although it is a small finding, it is also a serious problem.”

He suggested the risk should be treated in a similar way to the risk for suicidal thoughts or behaviors.

“Just as you might caution patients [initiating treatment with SSRIs] regarding that risk, you might broaden your counsel to include other types of violent behavior because the same process that provokes the risk of self-harm for a given person may be externalized and provoke harm or violence toward others.”

Ms. Lagerberg added that further research is needed to confirm their findings and “inform whether – and if so, how – clinical practice should change.”

The study was supported by the Swedish Research Council, Horizon 2020 ACTION project, Stockholm County Council, and Thurings Foundation. Ms. Lagerberg has reported no relevant financial relationships. Other author disclosures are listed in the article. Dr. Vieta and coauthors have reported no relevant financial relationships. Dr. Thase has reported consulting with and receiving research funding from many of the companies that manufacture/sell antidepressants.

This article first appeared on Medscape.com.

Selective serotonin reuptake inhibitors (SSRIs) are associated with an increased risk of committing a violent crime, an effect that may linger up to 12 weeks after treatment discontinuation, new research suggests. However, investigators say the finding should be interpreted with caution.

A large population-based study of more than 800,000 individuals showed those taking these antidepressants had an overall 2.7% increased risk of committing a violent crime while on the medications compared with when they were not taking them.

The increased risk persisted up to 12 weeks after discontinuing SSRIs and then returned to pretreatment levels. The risk was highest in younger individuals and those with a history of a prior violent crime.

“Our findings should be interpreted with caution [because] we do not know how far the association between SSRI medication and violent crime reflect causation,” lead author Tyra Lagerberg, MSc, a PhD candidate at Karolinska Institute, Sweden, said in an interview.

“Our findings should not be used as grounds for individuals to go off their [SSRI] medication or for clinicians to withhold medication from those who might benefit from it,” Ms. Lagerberg said.

The study was published online May 29 in European Neuropsychopharmacology.
 

Previous concerns

There has been “apprehension” about a possible association between SSRIs and elevated risk of aggression and violence, especially in young people, but it “remains unclear” if there is a similar risk in middle-aged and older adults, the authors noted. Moreover, it is unclear whether the risk of violence varies with time after initiating and discontinuing SSRI treatment.

To assess how the risk of violent crime might vary by age and time after SSRI treatment initiation and discontinuation, the researchers calculated absolute rates of violent crime per 1000 person-years during on- and off-treatment periods and also conducted within-group analyses.

The cohort, which was derived from several Swedish national registers, included all individuals in Sweden prescribed an SSRI between Jan. 1, 2006, and Dec. 31, 2013 (n = 785,337, 64.2% female) over an average follow-up of 7.3 years.

Some of the covariates used in the analyses included age, recent or previous violent crime, use of non-SSRI medications, sex, family income, education, county of residence, birth country, and lifetime diagnoses.
 

“Rare” effect

Almost the entire study cohort (99%) changed their SSRI treatment over the follow-up period. During this time, of the full study cohort, 2.7% committed violent crimes (21,203 crimes in 5,707,293 person-years).

More men than women were convicted of a violent crime (5.7% vs 1.0%, respectively).

Absolute rates of violent crime were lower in treated versus nontreated periods across all age categories (other than those between 15 and 24 years) when covariates were not taken into account.

However, when hazards during the on- and off-treatment periods were compared and adjusted for covariables, SSRI treatment was associated with a “modest increased” risk of violent crime (HR, 1.10) – particularly in those ages 15-25 years and ages 25–34 years (HR, 1.19 and 1.16, respectively).

Moreover, further analysis stratifying the cohort according to previous violent crime revealed that the elevated risk for violent crime convictions “seemed to be confined to the individuals with previous criminality,” compared to those with no criminal history (HR, 1.13 vs. 1.07).

The within-individual analysis included 2.6% of the overall cohort who experienced SSRI treatment switching as well as ≥1 violent event.

These individuals differed from the overall cohort in that they tended to be younger (close to half were aged 15-24 years compared with one quarter in the overall cohort) and predominantly male (77% vs. 36%, respectively).

When the hazard of violent crime was compared between individuals’ periods on and off medication, there was a significantly increased hazard during treatment in the whole cohort (HR, 1.26), but in particular, in those aged 25-34 years and 35-44 years (HR, 1.35 and 1.15, respectively).

The within-individual HRs remained elevated for up to 12 weeks post discontinuation of the SSRI (HR, 1.37 during the first 28 days; HR, 1.20 during days 29-84). Although women had a significantly elevated on-treatment hazard in the youngest age category, they had a lower incidence of crime across ages.

Treatment with benzodiazepines was associated with a significantly higher hazard of violent crime and treatment with non-SSRI antidepressants was associated with a “modest but nonsignificantly elevated” hazard.

By contrast, treatment with other psychotropic drugs was not associated with elevated risk.
 

Warn patients

Commenting on the study, Eduard Vieta, MD, PhD, professor of psychiatry, Institute of Neuroscience, University of Barcelona, Spain, and author of an accompanying editorial, said it’s still not known if the mediating factor in the increased risk of violent crime was the SSRI or the underlying mental condition that prompted the prescription.

Dr. Vieta, who was not involved with the study, added that the results “raise a note of caution in terms of making a very accurate diagnosis and treatment in patients with a history of conviction, violence, or criminality, and opting ideally for psychosocial therapies whenever possible in this population.”

Also commenting on the study, Michael Thase, MD, professor of psychiatry, University of Pennsylvania, Philadelphia, said the findings are “not easy to brush away or explain away.”

Dr. Thase, who was not involved with the study, continued, “although it is a small finding, it is also a serious problem.”

He suggested the risk should be treated in a similar way to the risk for suicidal thoughts or behaviors.

“Just as you might caution patients [initiating treatment with SSRIs] regarding that risk, you might broaden your counsel to include other types of violent behavior because the same process that provokes the risk of self-harm for a given person may be externalized and provoke harm or violence toward others.”

Ms. Lagerberg added that further research is needed to confirm their findings and “inform whether – and if so, how – clinical practice should change.”

The study was supported by the Swedish Research Council, Horizon 2020 ACTION project, Stockholm County Council, and Thurings Foundation. Ms. Lagerberg has reported no relevant financial relationships. Other author disclosures are listed in the article. Dr. Vieta and coauthors have reported no relevant financial relationships. Dr. Thase has reported consulting with and receiving research funding from many of the companies that manufacture/sell antidepressants.

This article first appeared on Medscape.com.

Selective serotonin reuptake inhibitors (SSRIs) are associated with an increased risk of committing a violent crime, an effect that may linger up to 12 weeks after treatment discontinuation, new research suggests. However, investigators say the finding should be interpreted with caution.

A large population-based study of more than 800,000 individuals showed those taking these antidepressants had an overall 2.7% increased risk of committing a violent crime while on the medications compared with when they were not taking them.

The increased risk persisted up to 12 weeks after discontinuing SSRIs and then returned to pretreatment levels. The risk was highest in younger individuals and those with a history of a prior violent crime.

“Our findings should be interpreted with caution [because] we do not know how far the association between SSRI medication and violent crime reflect causation,” lead author Tyra Lagerberg, MSc, a PhD candidate at Karolinska Institute, Sweden, said in an interview.

“Our findings should not be used as grounds for individuals to go off their [SSRI] medication or for clinicians to withhold medication from those who might benefit from it,” Ms. Lagerberg said.

The study was published online May 29 in European Neuropsychopharmacology.
 

Previous concerns

There has been “apprehension” about a possible association between SSRIs and elevated risk of aggression and violence, especially in young people, but it “remains unclear” if there is a similar risk in middle-aged and older adults, the authors noted. Moreover, it is unclear whether the risk of violence varies with time after initiating and discontinuing SSRI treatment.

To assess how the risk of violent crime might vary by age and time after SSRI treatment initiation and discontinuation, the researchers calculated absolute rates of violent crime per 1000 person-years during on- and off-treatment periods and also conducted within-group analyses.

The cohort, which was derived from several Swedish national registers, included all individuals in Sweden prescribed an SSRI between Jan. 1, 2006, and Dec. 31, 2013 (n = 785,337, 64.2% female) over an average follow-up of 7.3 years.

Some of the covariates used in the analyses included age, recent or previous violent crime, use of non-SSRI medications, sex, family income, education, county of residence, birth country, and lifetime diagnoses.
 

“Rare” effect

Almost the entire study cohort (99%) changed their SSRI treatment over the follow-up period. During this time, of the full study cohort, 2.7% committed violent crimes (21,203 crimes in 5,707,293 person-years).

More men than women were convicted of a violent crime (5.7% vs 1.0%, respectively).

Absolute rates of violent crime were lower in treated versus nontreated periods across all age categories (other than those between 15 and 24 years) when covariates were not taken into account.

However, when hazards during the on- and off-treatment periods were compared and adjusted for covariables, SSRI treatment was associated with a “modest increased” risk of violent crime (HR, 1.10) – particularly in those ages 15-25 years and ages 25–34 years (HR, 1.19 and 1.16, respectively).

Moreover, further analysis stratifying the cohort according to previous violent crime revealed that the elevated risk for violent crime convictions “seemed to be confined to the individuals with previous criminality,” compared to those with no criminal history (HR, 1.13 vs. 1.07).

The within-individual analysis included 2.6% of the overall cohort who experienced SSRI treatment switching as well as ≥1 violent event.

These individuals differed from the overall cohort in that they tended to be younger (close to half were aged 15-24 years compared with one quarter in the overall cohort) and predominantly male (77% vs. 36%, respectively).

When the hazard of violent crime was compared between individuals’ periods on and off medication, there was a significantly increased hazard during treatment in the whole cohort (HR, 1.26), but in particular, in those aged 25-34 years and 35-44 years (HR, 1.35 and 1.15, respectively).

The within-individual HRs remained elevated for up to 12 weeks post discontinuation of the SSRI (HR, 1.37 during the first 28 days; HR, 1.20 during days 29-84). Although women had a significantly elevated on-treatment hazard in the youngest age category, they had a lower incidence of crime across ages.

Treatment with benzodiazepines was associated with a significantly higher hazard of violent crime and treatment with non-SSRI antidepressants was associated with a “modest but nonsignificantly elevated” hazard.

By contrast, treatment with other psychotropic drugs was not associated with elevated risk.
 

Warn patients

Commenting on the study, Eduard Vieta, MD, PhD, professor of psychiatry, Institute of Neuroscience, University of Barcelona, Spain, and author of an accompanying editorial, said it’s still not known if the mediating factor in the increased risk of violent crime was the SSRI or the underlying mental condition that prompted the prescription.

Dr. Vieta, who was not involved with the study, added that the results “raise a note of caution in terms of making a very accurate diagnosis and treatment in patients with a history of conviction, violence, or criminality, and opting ideally for psychosocial therapies whenever possible in this population.”

Also commenting on the study, Michael Thase, MD, professor of psychiatry, University of Pennsylvania, Philadelphia, said the findings are “not easy to brush away or explain away.”

Dr. Thase, who was not involved with the study, continued, “although it is a small finding, it is also a serious problem.”

He suggested the risk should be treated in a similar way to the risk for suicidal thoughts or behaviors.

“Just as you might caution patients [initiating treatment with SSRIs] regarding that risk, you might broaden your counsel to include other types of violent behavior because the same process that provokes the risk of self-harm for a given person may be externalized and provoke harm or violence toward others.”

Ms. Lagerberg added that further research is needed to confirm their findings and “inform whether – and if so, how – clinical practice should change.”

The study was supported by the Swedish Research Council, Horizon 2020 ACTION project, Stockholm County Council, and Thurings Foundation. Ms. Lagerberg has reported no relevant financial relationships. Other author disclosures are listed in the article. Dr. Vieta and coauthors have reported no relevant financial relationships. Dr. Thase has reported consulting with and receiving research funding from many of the companies that manufacture/sell antidepressants.

This article first appeared on Medscape.com.

Two new clinical guidance documents from the American College of Rheumatology provide evidence-based recommendations for managing pediatric rheumatic disease during the COVID-19 pandemic as well as diagnostic and treatment recommendations for multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 infection.

Although several children’s hospitals have published their treatment protocols for MIS-C since the condition’s initial discovery, the ACR appears to be the first medical organization to review all the most current evidence to issue interim guidance with the expectations that it will change as more data become available.

“It is challenging having to make recommendations not having a lot of scientific evidence, but we still felt we had to use whatever’s out there to the best of our ability and use our experience to put together these recommendations,” Dawn M. Wahezi, MD, chief of pediatric rheumatology at Children’s Hospital at Montefiore and an associate professor of pediatrics at Albert Einstein College of Medicine, New York, said in an interview.

“We wanted to be mindful of the fact that there are things we know and things we don’t know, and we have to be careful about what we’re recommending,” said Dr. Wahezi, a member of the ACR working group that assembled the recommendations for pediatric rheumatic disease management during the pandemic. “We’re recommending the best we can at this moment, but if there are new studies that come out and suggest otherwise, we will definitely have to go back and amend the document.”

The foremost priority of the pediatric rheumatic disease guidance focuses on maintaining control of the disease and avoiding flares that may put children at greater risk of infection. Dr. Wahezi said the ACR has received many calls from patients and clinicians asking whether patients should continue their immunosuppressant medications. Fear of the coronavirus infection, medication shortages, difficulty getting to the pharmacy, uneasiness about going to the clinic or hospital for infusions, and other barriers may have led to gaps in medication.

“We didn’t want people to be too quick to hold patients’ medications just because they were scared of COVID,” Dr. Wahezi said. “If they did have medication stopped for one reason or another and their disease flared, having active disease, regardless of which disease it is, actually puts you at higher risk for infection. By controlling their disease, that would be the way to protect them the most.”

A key takeaway in the guidance on MIS-C, meanwhile, is an emphasis on its rarity lest physicians be too quick to diagnose it and miss another serious condition with overlapping symptoms, explained Lauren Henderson, MD, an attending rheumatologist at Boston Children’s Hospital and assistant professor of pediatrics at Harvard Medical School, Boston. Dr. Henderson participated in the ACR group that wrote the MIS-C guidance.

“The first thing we want to be thoughtful about clinically is to recognize that children in general with the acute infectious phase of SARS-CoV-2 have mild symptoms and generally do well,” Dr. Henderson said. “From what we can tell from all the data, MIS-C is rare. That really needs to be considered when clinicians on the ground are doing the diagnostic evaluation” because of concerns that clinicians “could rush to diagnose and treat patients with MIS-C and miss important diagnoses like malignancies and infections.”

Management of pediatric rheumatic disease during the pandemic

The COVID-19 clinical guidance for managing pediatric rheumatic disease grew from the work of the North American Pediatric Rheumatology Clinical Guidance Task Force, which included seven pediatric rheumatologists, two pediatric infectious disease physicians, one adult rheumatologist, and one pediatric nurse practitioner. The general guidance covers usual preventive measures for reducing risk for COVID-19 infection, the recommendation that children continue to receive recommended vaccines unless contraindicated by medication, and routine in-person visits for ophthalmologic surveillance of those with a history of uveitis or at high risk for chronic uveitis. The guidance also notes the risk of mental health concerns, such as depression and anxiety, related to quarantine and the pandemic.

The top recommendation is initiation or continuation of all medications necessary to control underlying disease, including NSAIDs, hydroxychloroquine, ACE inhibitors/angiotensin II receptor blockers, colchicine, conventional disease-modifying antirheumatic drugs (cDMARDs), biologic DMARDs, and targeted synthetic DMARDs. Even patients who may have had exposure to COVID-19 or who have an asymptomatic COVID-19 infection should continue to take these medications with the exception of ACEi/ARBs.

In those with pediatric rheumatic disease who have a symptomatic COVID-19 infection, “NSAIDs, HCQ, and colchicine may be continued, if necessary, to control underlying disease,” as can interleukin (IL)-1 and IL-6 inhibitors, but “cDMARDs, bDMARDs [except IL-1 and IL-6 inhibitors] and tsDMARDs should be temporarily delayed or withheld,” according to the guidance. Glucocorticoids can be continued at the lowest possible dose to control disease.

“There’s nothing in the literature that suggests people who have rheumatic disease, especially children, and people who are on these medications, really are at increased risk for COVID-19,” Dr. Wahezi said. “That’s why we didn’t want people to be overcautious in stopping medications when the main priority is to control their disease.”

She noted some experts’ speculations that these medications may actually benefit patients with rheumatic disease who develop a COVID-19 infection because the medications keep the immune response in check. “If you allow them to have this dysregulated immune response and have active disease, you’re potentially putting them at greater risk,” Dr. Wahezi said, although she stressed that inadequate evidence exists to support these speculations right now.

Lack of evidence has been the biggest challenge all around with developing this guidance, she said.

“Because this is such an unprecedented situation and because people are so desperate to find treatments both for the illness and to protect those at risk for it, there are lots of people trying to put evidence out there, but it may not be the best-quality evidence,” Dr. Wahezi said.

Insufficient evidence also drove the group’s determination that “SARS-CoV-2 antibody testing is not useful in informing on the history of infection or risk of reinfection,” as the guidance states. Too much variability in the assays exist, Dr. Wahezi said, and, further, it’s unclear what the clinical significance of a positive test would be.

“We didn’t want anyone to feel they had to make clinical decisions based on the results of that antibody testing,” she said. “Even if the test is accurate, we don’t know how to interpret it because it’s so new.”

The guidance also notes that patients with stable disease and previously stable lab markers on stable doses of their medication may be able to extend the interval for medication toxicity lab testing a few months if there is concern about exposure to COVID-19 to get the blood work.

“If you’re just starting a medicine or there’s someone who’s had abnormalities with the medicine in the past or you’re making medication adjustments, you wouldn’t do it in those scenarios, but if there’s someone who’s been on the drug for a long time and are nervous to get [blood] drawn, it’s probably okay to delay it,” Dr. Wahezi said. Lab work for disease activity measures, on the other hand, remain particularly important, especially since telemedicine visits may require clinicians to rely on lab results more than previously.

Management of MIS-C associated with COVID-19

The task force that developed guidance for the new inflammatory condition recently linked to SARS-CoV-2 infections in children included nine pediatric rheumatologists, two adult rheumatologists, two pediatric cardiologists, two pediatric infectious disease specialists, and one pediatric critical care physician.

The guidance includes a figure for the diagnostic pathway in evaluating children suspected of having MIS-C and extensive detail on diagnostic work-up, but the task force intentionally avoided providing a case definition for the condition. Existing case definitions from the Centers for Disease Control and Prevention, World Health Organization, and the United Kingdom’s Royal College of Paediatrics and Child Health differ from one another and are based on unclear evidence, Dr. Henderson noted. “We really don’t have enough data to know the sensitivity and specificity of each parameter, and until that’s available, we didn’t want to add to the confusion,” she said.

The guidance also stresses that MIS-C is a rare complication, so patients suspected of having the condition who do not have “life-threatening manifestations should undergo diagnostic evaluation for MIS-C as well as other possible infectious and noninfectious etiologies before immunomodulatory treatment is initiated,” the guidance states.

Unless a child is in shock or otherwise requires urgent care, physicians should take the time to complete the diagnostic work-up while monitoring the child, Dr. Henderson said. If the child does have MIS-C, the guidance currently recommends intravenous immunoglobulin (IVIG) and/or glucocorticoids to prevent coronary artery aneurysms, the same treatment other institutions have been recommending.

“We don’t have rigorous comparative studies looking at different types of treatments,” Dr. Henderson said, noting that the vast majority of children in the literature received IVIG and/or glucocorticoid treatment. “Often children really responded quite forcefully to those treatments, but we don’t have high-quality data yet to know that this treatment is better than supportive care or another medication.”

Dr. Henderson also stressed the importance of children receiving care at a facility with the necessary expertise to manage MIS-C and receiving long-term follow-up care from a multidisciplinary clinical team that includes a rheumatologist, an infectious disease doctor, a cardiologist, and possibly a hematologist.

“Making sure children are admitted to a hospital that has the resources and are followed by physicians with expertise or understanding of the intricacies of MIS-C is really important,” she said, particularly for children with cardiac involvement. “We don’t know if all the kids presenting with left ventricular dysfunction and shock are at risk for having myocardial fibrosis down the line,” she noted. “There is so much we do not understand and very little data to guide us on what to do, so these children really need to be under the care of a cardiologist and rheumatologist to make sure that their care is tailored to them.”

Although MIS-C shares overlapping symptoms with Kawasaki disease, it’s still unclear how similar or different the two conditions are, Dr. Henderson said.

“We can definitely say that when we look at MIS-C and compare it to historical groups of Kawasaki disease before the pandemic, there are definitely different features in the MIS-C group,” she said. Kawasaki disease generally only affects children under age 5, whereas MIS-C patients run the gamut from age 1-17. Racial demographics are also different, with a higher proportion of black children affected by MIS-C.

It’s possible that the pathophysiology of both conditions will turn out to be similar, particularly given the hypothesis that Kawasaki disease is triggered by infections in genetically predisposed people. However, the severity of symptoms and risk of aneurysms appear greater with MIS-C so far.

“The degree to which these patients are presenting with left ventricular dysfunction and shock is much higher than what we’ve seen previously,” Dr. Henderson said. “Children can have aneurysms even if they don’t meet all the Kawasaki disease features, which makes it feel that this is somehow clinically different from what we’ve seen before. It’s not just the kids who have the rash and the conjunctivitis and the extremity changes and oral changes who have the aneurysms.”

The reason for including both IVIG and glucocorticoids as possible first-line drugs to prevent aneurysms is that some evidence suggests children with MIS-C may have higher levels of IVIG resistance, she said.

Like Dr. Wahezi, Dr. Henderson emphasized the necessarily transient nature of these recommendations.

“These recommendations will almost certainly change based on evolving understanding of MIS-C and the data,” Dr. Henderson said, adding that this new, unique condition highlights the importance of including children in allocating funding for research and in clinical trials.

“Children are not always identical to adults, and it’s really important that we have high-quality data to inform our decisions about how to care for them,” she said.

Dr. Wahezi had no disclosures. Dr. Henderson has consulted for Sobi and Adaptive Technologies. The guidelines did not note other disclosures for members of the ACR groups.

SOURCES: COVID-19 Clinical Guidance for Pediatric Patients with Rheumatic Disease and Clinical Guidance for Pediatric Patients with Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with SARS-CoV-2 and Hyperinflammation in COVID-19

Two new clinical guidance documents from the American College of Rheumatology provide evidence-based recommendations for managing pediatric rheumatic disease during the COVID-19 pandemic as well as diagnostic and treatment recommendations for multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 infection.

Although several children’s hospitals have published their treatment protocols for MIS-C since the condition’s initial discovery, the ACR appears to be the first medical organization to review all the most current evidence to issue interim guidance with the expectations that it will change as more data become available.

“It is challenging having to make recommendations not having a lot of scientific evidence, but we still felt we had to use whatever’s out there to the best of our ability and use our experience to put together these recommendations,” Dawn M. Wahezi, MD, chief of pediatric rheumatology at Children’s Hospital at Montefiore and an associate professor of pediatrics at Albert Einstein College of Medicine, New York, said in an interview.

“We wanted to be mindful of the fact that there are things we know and things we don’t know, and we have to be careful about what we’re recommending,” said Dr. Wahezi, a member of the ACR working group that assembled the recommendations for pediatric rheumatic disease management during the pandemic. “We’re recommending the best we can at this moment, but if there are new studies that come out and suggest otherwise, we will definitely have to go back and amend the document.”

The foremost priority of the pediatric rheumatic disease guidance focuses on maintaining control of the disease and avoiding flares that may put children at greater risk of infection. Dr. Wahezi said the ACR has received many calls from patients and clinicians asking whether patients should continue their immunosuppressant medications. Fear of the coronavirus infection, medication shortages, difficulty getting to the pharmacy, uneasiness about going to the clinic or hospital for infusions, and other barriers may have led to gaps in medication.

“We didn’t want people to be too quick to hold patients’ medications just because they were scared of COVID,” Dr. Wahezi said. “If they did have medication stopped for one reason or another and their disease flared, having active disease, regardless of which disease it is, actually puts you at higher risk for infection. By controlling their disease, that would be the way to protect them the most.”

A key takeaway in the guidance on MIS-C, meanwhile, is an emphasis on its rarity lest physicians be too quick to diagnose it and miss another serious condition with overlapping symptoms, explained Lauren Henderson, MD, an attending rheumatologist at Boston Children’s Hospital and assistant professor of pediatrics at Harvard Medical School, Boston. Dr. Henderson participated in the ACR group that wrote the MIS-C guidance.

“The first thing we want to be thoughtful about clinically is to recognize that children in general with the acute infectious phase of SARS-CoV-2 have mild symptoms and generally do well,” Dr. Henderson said. “From what we can tell from all the data, MIS-C is rare. That really needs to be considered when clinicians on the ground are doing the diagnostic evaluation” because of concerns that clinicians “could rush to diagnose and treat patients with MIS-C and miss important diagnoses like malignancies and infections.”

Management of pediatric rheumatic disease during the pandemic

The COVID-19 clinical guidance for managing pediatric rheumatic disease grew from the work of the North American Pediatric Rheumatology Clinical Guidance Task Force, which included seven pediatric rheumatologists, two pediatric infectious disease physicians, one adult rheumatologist, and one pediatric nurse practitioner. The general guidance covers usual preventive measures for reducing risk for COVID-19 infection, the recommendation that children continue to receive recommended vaccines unless contraindicated by medication, and routine in-person visits for ophthalmologic surveillance of those with a history of uveitis or at high risk for chronic uveitis. The guidance also notes the risk of mental health concerns, such as depression and anxiety, related to quarantine and the pandemic.

The top recommendation is initiation or continuation of all medications necessary to control underlying disease, including NSAIDs, hydroxychloroquine, ACE inhibitors/angiotensin II receptor blockers, colchicine, conventional disease-modifying antirheumatic drugs (cDMARDs), biologic DMARDs, and targeted synthetic DMARDs. Even patients who may have had exposure to COVID-19 or who have an asymptomatic COVID-19 infection should continue to take these medications with the exception of ACEi/ARBs.

In those with pediatric rheumatic disease who have a symptomatic COVID-19 infection, “NSAIDs, HCQ, and colchicine may be continued, if necessary, to control underlying disease,” as can interleukin (IL)-1 and IL-6 inhibitors, but “cDMARDs, bDMARDs [except IL-1 and IL-6 inhibitors] and tsDMARDs should be temporarily delayed or withheld,” according to the guidance. Glucocorticoids can be continued at the lowest possible dose to control disease.

“There’s nothing in the literature that suggests people who have rheumatic disease, especially children, and people who are on these medications, really are at increased risk for COVID-19,” Dr. Wahezi said. “That’s why we didn’t want people to be overcautious in stopping medications when the main priority is to control their disease.”

She noted some experts’ speculations that these medications may actually benefit patients with rheumatic disease who develop a COVID-19 infection because the medications keep the immune response in check. “If you allow them to have this dysregulated immune response and have active disease, you’re potentially putting them at greater risk,” Dr. Wahezi said, although she stressed that inadequate evidence exists to support these speculations right now.

Lack of evidence has been the biggest challenge all around with developing this guidance, she said.

“Because this is such an unprecedented situation and because people are so desperate to find treatments both for the illness and to protect those at risk for it, there are lots of people trying to put evidence out there, but it may not be the best-quality evidence,” Dr. Wahezi said.

Insufficient evidence also drove the group’s determination that “SARS-CoV-2 antibody testing is not useful in informing on the history of infection or risk of reinfection,” as the guidance states. Too much variability in the assays exist, Dr. Wahezi said, and, further, it’s unclear what the clinical significance of a positive test would be.

“We didn’t want anyone to feel they had to make clinical decisions based on the results of that antibody testing,” she said. “Even if the test is accurate, we don’t know how to interpret it because it’s so new.”

The guidance also notes that patients with stable disease and previously stable lab markers on stable doses of their medication may be able to extend the interval for medication toxicity lab testing a few months if there is concern about exposure to COVID-19 to get the blood work.

“If you’re just starting a medicine or there’s someone who’s had abnormalities with the medicine in the past or you’re making medication adjustments, you wouldn’t do it in those scenarios, but if there’s someone who’s been on the drug for a long time and are nervous to get [blood] drawn, it’s probably okay to delay it,” Dr. Wahezi said. Lab work for disease activity measures, on the other hand, remain particularly important, especially since telemedicine visits may require clinicians to rely on lab results more than previously.

Management of MIS-C associated with COVID-19

The task force that developed guidance for the new inflammatory condition recently linked to SARS-CoV-2 infections in children included nine pediatric rheumatologists, two adult rheumatologists, two pediatric cardiologists, two pediatric infectious disease specialists, and one pediatric critical care physician.

The guidance includes a figure for the diagnostic pathway in evaluating children suspected of having MIS-C and extensive detail on diagnostic work-up, but the task force intentionally avoided providing a case definition for the condition. Existing case definitions from the Centers for Disease Control and Prevention, World Health Organization, and the United Kingdom’s Royal College of Paediatrics and Child Health differ from one another and are based on unclear evidence, Dr. Henderson noted. “We really don’t have enough data to know the sensitivity and specificity of each parameter, and until that’s available, we didn’t want to add to the confusion,” she said.

The guidance also stresses that MIS-C is a rare complication, so patients suspected of having the condition who do not have “life-threatening manifestations should undergo diagnostic evaluation for MIS-C as well as other possible infectious and noninfectious etiologies before immunomodulatory treatment is initiated,” the guidance states.

Unless a child is in shock or otherwise requires urgent care, physicians should take the time to complete the diagnostic work-up while monitoring the child, Dr. Henderson said. If the child does have MIS-C, the guidance currently recommends intravenous immunoglobulin (IVIG) and/or glucocorticoids to prevent coronary artery aneurysms, the same treatment other institutions have been recommending.

“We don’t have rigorous comparative studies looking at different types of treatments,” Dr. Henderson said, noting that the vast majority of children in the literature received IVIG and/or glucocorticoid treatment. “Often children really responded quite forcefully to those treatments, but we don’t have high-quality data yet to know that this treatment is better than supportive care or another medication.”

Dr. Henderson also stressed the importance of children receiving care at a facility with the necessary expertise to manage MIS-C and receiving long-term follow-up care from a multidisciplinary clinical team that includes a rheumatologist, an infectious disease doctor, a cardiologist, and possibly a hematologist.

“Making sure children are admitted to a hospital that has the resources and are followed by physicians with expertise or understanding of the intricacies of MIS-C is really important,” she said, particularly for children with cardiac involvement. “We don’t know if all the kids presenting with left ventricular dysfunction and shock are at risk for having myocardial fibrosis down the line,” she noted. “There is so much we do not understand and very little data to guide us on what to do, so these children really need to be under the care of a cardiologist and rheumatologist to make sure that their care is tailored to them.”

Although MIS-C shares overlapping symptoms with Kawasaki disease, it’s still unclear how similar or different the two conditions are, Dr. Henderson said.

“We can definitely say that when we look at MIS-C and compare it to historical groups of Kawasaki disease before the pandemic, there are definitely different features in the MIS-C group,” she said. Kawasaki disease generally only affects children under age 5, whereas MIS-C patients run the gamut from age 1-17. Racial demographics are also different, with a higher proportion of black children affected by MIS-C.

It’s possible that the pathophysiology of both conditions will turn out to be similar, particularly given the hypothesis that Kawasaki disease is triggered by infections in genetically predisposed people. However, the severity of symptoms and risk of aneurysms appear greater with MIS-C so far.

“The degree to which these patients are presenting with left ventricular dysfunction and shock is much higher than what we’ve seen previously,” Dr. Henderson said. “Children can have aneurysms even if they don’t meet all the Kawasaki disease features, which makes it feel that this is somehow clinically different from what we’ve seen before. It’s not just the kids who have the rash and the conjunctivitis and the extremity changes and oral changes who have the aneurysms.”

The reason for including both IVIG and glucocorticoids as possible first-line drugs to prevent aneurysms is that some evidence suggests children with MIS-C may have higher levels of IVIG resistance, she said.

Like Dr. Wahezi, Dr. Henderson emphasized the necessarily transient nature of these recommendations.

“These recommendations will almost certainly change based on evolving understanding of MIS-C and the data,” Dr. Henderson said, adding that this new, unique condition highlights the importance of including children in allocating funding for research and in clinical trials.

“Children are not always identical to adults, and it’s really important that we have high-quality data to inform our decisions about how to care for them,” she said.

Dr. Wahezi had no disclosures. Dr. Henderson has consulted for Sobi and Adaptive Technologies. The guidelines did not note other disclosures for members of the ACR groups.

SOURCES: COVID-19 Clinical Guidance for Pediatric Patients with Rheumatic Disease and Clinical Guidance for Pediatric Patients with Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with SARS-CoV-2 and Hyperinflammation in COVID-19

Two new clinical guidance documents from the American College of Rheumatology provide evidence-based recommendations for managing pediatric rheumatic disease during the COVID-19 pandemic as well as diagnostic and treatment recommendations for multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 infection.

Although several children’s hospitals have published their treatment protocols for MIS-C since the condition’s initial discovery, the ACR appears to be the first medical organization to review all the most current evidence to issue interim guidance with the expectations that it will change as more data become available.

“It is challenging having to make recommendations not having a lot of scientific evidence, but we still felt we had to use whatever’s out there to the best of our ability and use our experience to put together these recommendations,” Dawn M. Wahezi, MD, chief of pediatric rheumatology at Children’s Hospital at Montefiore and an associate professor of pediatrics at Albert Einstein College of Medicine, New York, said in an interview.

“We wanted to be mindful of the fact that there are things we know and things we don’t know, and we have to be careful about what we’re recommending,” said Dr. Wahezi, a member of the ACR working group that assembled the recommendations for pediatric rheumatic disease management during the pandemic. “We’re recommending the best we can at this moment, but if there are new studies that come out and suggest otherwise, we will definitely have to go back and amend the document.”

The foremost priority of the pediatric rheumatic disease guidance focuses on maintaining control of the disease and avoiding flares that may put children at greater risk of infection. Dr. Wahezi said the ACR has received many calls from patients and clinicians asking whether patients should continue their immunosuppressant medications. Fear of the coronavirus infection, medication shortages, difficulty getting to the pharmacy, uneasiness about going to the clinic or hospital for infusions, and other barriers may have led to gaps in medication.

“We didn’t want people to be too quick to hold patients’ medications just because they were scared of COVID,” Dr. Wahezi said. “If they did have medication stopped for one reason or another and their disease flared, having active disease, regardless of which disease it is, actually puts you at higher risk for infection. By controlling their disease, that would be the way to protect them the most.”

A key takeaway in the guidance on MIS-C, meanwhile, is an emphasis on its rarity lest physicians be too quick to diagnose it and miss another serious condition with overlapping symptoms, explained Lauren Henderson, MD, an attending rheumatologist at Boston Children’s Hospital and assistant professor of pediatrics at Harvard Medical School, Boston. Dr. Henderson participated in the ACR group that wrote the MIS-C guidance.

“The first thing we want to be thoughtful about clinically is to recognize that children in general with the acute infectious phase of SARS-CoV-2 have mild symptoms and generally do well,” Dr. Henderson said. “From what we can tell from all the data, MIS-C is rare. That really needs to be considered when clinicians on the ground are doing the diagnostic evaluation” because of concerns that clinicians “could rush to diagnose and treat patients with MIS-C and miss important diagnoses like malignancies and infections.”

Management of pediatric rheumatic disease during the pandemic

The COVID-19 clinical guidance for managing pediatric rheumatic disease grew from the work of the North American Pediatric Rheumatology Clinical Guidance Task Force, which included seven pediatric rheumatologists, two pediatric infectious disease physicians, one adult rheumatologist, and one pediatric nurse practitioner. The general guidance covers usual preventive measures for reducing risk for COVID-19 infection, the recommendation that children continue to receive recommended vaccines unless contraindicated by medication, and routine in-person visits for ophthalmologic surveillance of those with a history of uveitis or at high risk for chronic uveitis. The guidance also notes the risk of mental health concerns, such as depression and anxiety, related to quarantine and the pandemic.

The top recommendation is initiation or continuation of all medications necessary to control underlying disease, including NSAIDs, hydroxychloroquine, ACE inhibitors/angiotensin II receptor blockers, colchicine, conventional disease-modifying antirheumatic drugs (cDMARDs), biologic DMARDs, and targeted synthetic DMARDs. Even patients who may have had exposure to COVID-19 or who have an asymptomatic COVID-19 infection should continue to take these medications with the exception of ACEi/ARBs.

In those with pediatric rheumatic disease who have a symptomatic COVID-19 infection, “NSAIDs, HCQ, and colchicine may be continued, if necessary, to control underlying disease,” as can interleukin (IL)-1 and IL-6 inhibitors, but “cDMARDs, bDMARDs [except IL-1 and IL-6 inhibitors] and tsDMARDs should be temporarily delayed or withheld,” according to the guidance. Glucocorticoids can be continued at the lowest possible dose to control disease.

“There’s nothing in the literature that suggests people who have rheumatic disease, especially children, and people who are on these medications, really are at increased risk for COVID-19,” Dr. Wahezi said. “That’s why we didn’t want people to be overcautious in stopping medications when the main priority is to control their disease.”

She noted some experts’ speculations that these medications may actually benefit patients with rheumatic disease who develop a COVID-19 infection because the medications keep the immune response in check. “If you allow them to have this dysregulated immune response and have active disease, you’re potentially putting them at greater risk,” Dr. Wahezi said, although she stressed that inadequate evidence exists to support these speculations right now.

Lack of evidence has been the biggest challenge all around with developing this guidance, she said.

“Because this is such an unprecedented situation and because people are so desperate to find treatments both for the illness and to protect those at risk for it, there are lots of people trying to put evidence out there, but it may not be the best-quality evidence,” Dr. Wahezi said.

Insufficient evidence also drove the group’s determination that “SARS-CoV-2 antibody testing is not useful in informing on the history of infection or risk of reinfection,” as the guidance states. Too much variability in the assays exist, Dr. Wahezi said, and, further, it’s unclear what the clinical significance of a positive test would be.

“We didn’t want anyone to feel they had to make clinical decisions based on the results of that antibody testing,” she said. “Even if the test is accurate, we don’t know how to interpret it because it’s so new.”

The guidance also notes that patients with stable disease and previously stable lab markers on stable doses of their medication may be able to extend the interval for medication toxicity lab testing a few months if there is concern about exposure to COVID-19 to get the blood work.

“If you’re just starting a medicine or there’s someone who’s had abnormalities with the medicine in the past or you’re making medication adjustments, you wouldn’t do it in those scenarios, but if there’s someone who’s been on the drug for a long time and are nervous to get [blood] drawn, it’s probably okay to delay it,” Dr. Wahezi said. Lab work for disease activity measures, on the other hand, remain particularly important, especially since telemedicine visits may require clinicians to rely on lab results more than previously.

Management of MIS-C associated with COVID-19

The task force that developed guidance for the new inflammatory condition recently linked to SARS-CoV-2 infections in children included nine pediatric rheumatologists, two adult rheumatologists, two pediatric cardiologists, two pediatric infectious disease specialists, and one pediatric critical care physician.

The guidance includes a figure for the diagnostic pathway in evaluating children suspected of having MIS-C and extensive detail on diagnostic work-up, but the task force intentionally avoided providing a case definition for the condition. Existing case definitions from the Centers for Disease Control and Prevention, World Health Organization, and the United Kingdom’s Royal College of Paediatrics and Child Health differ from one another and are based on unclear evidence, Dr. Henderson noted. “We really don’t have enough data to know the sensitivity and specificity of each parameter, and until that’s available, we didn’t want to add to the confusion,” she said.

The guidance also stresses that MIS-C is a rare complication, so patients suspected of having the condition who do not have “life-threatening manifestations should undergo diagnostic evaluation for MIS-C as well as other possible infectious and noninfectious etiologies before immunomodulatory treatment is initiated,” the guidance states.

Unless a child is in shock or otherwise requires urgent care, physicians should take the time to complete the diagnostic work-up while monitoring the child, Dr. Henderson said. If the child does have MIS-C, the guidance currently recommends intravenous immunoglobulin (IVIG) and/or glucocorticoids to prevent coronary artery aneurysms, the same treatment other institutions have been recommending.

“We don’t have rigorous comparative studies looking at different types of treatments,” Dr. Henderson said, noting that the vast majority of children in the literature received IVIG and/or glucocorticoid treatment. “Often children really responded quite forcefully to those treatments, but we don’t have high-quality data yet to know that this treatment is better than supportive care or another medication.”

Dr. Henderson also stressed the importance of children receiving care at a facility with the necessary expertise to manage MIS-C and receiving long-term follow-up care from a multidisciplinary clinical team that includes a rheumatologist, an infectious disease doctor, a cardiologist, and possibly a hematologist.

“Making sure children are admitted to a hospital that has the resources and are followed by physicians with expertise or understanding of the intricacies of MIS-C is really important,” she said, particularly for children with cardiac involvement. “We don’t know if all the kids presenting with left ventricular dysfunction and shock are at risk for having myocardial fibrosis down the line,” she noted. “There is so much we do not understand and very little data to guide us on what to do, so these children really need to be under the care of a cardiologist and rheumatologist to make sure that their care is tailored to them.”

Although MIS-C shares overlapping symptoms with Kawasaki disease, it’s still unclear how similar or different the two conditions are, Dr. Henderson said.

“We can definitely say that when we look at MIS-C and compare it to historical groups of Kawasaki disease before the pandemic, there are definitely different features in the MIS-C group,” she said. Kawasaki disease generally only affects children under age 5, whereas MIS-C patients run the gamut from age 1-17. Racial demographics are also different, with a higher proportion of black children affected by MIS-C.

It’s possible that the pathophysiology of both conditions will turn out to be similar, particularly given the hypothesis that Kawasaki disease is triggered by infections in genetically predisposed people. However, the severity of symptoms and risk of aneurysms appear greater with MIS-C so far.

“The degree to which these patients are presenting with left ventricular dysfunction and shock is much higher than what we’ve seen previously,” Dr. Henderson said. “Children can have aneurysms even if they don’t meet all the Kawasaki disease features, which makes it feel that this is somehow clinically different from what we’ve seen before. It’s not just the kids who have the rash and the conjunctivitis and the extremity changes and oral changes who have the aneurysms.”

The reason for including both IVIG and glucocorticoids as possible first-line drugs to prevent aneurysms is that some evidence suggests children with MIS-C may have higher levels of IVIG resistance, she said.

Like Dr. Wahezi, Dr. Henderson emphasized the necessarily transient nature of these recommendations.

“These recommendations will almost certainly change based on evolving understanding of MIS-C and the data,” Dr. Henderson said, adding that this new, unique condition highlights the importance of including children in allocating funding for research and in clinical trials.

“Children are not always identical to adults, and it’s really important that we have high-quality data to inform our decisions about how to care for them,” she said.

Dr. Wahezi had no disclosures. Dr. Henderson has consulted for Sobi and Adaptive Technologies. The guidelines did not note other disclosures for members of the ACR groups.

SOURCES: COVID-19 Clinical Guidance for Pediatric Patients with Rheumatic Disease and Clinical Guidance for Pediatric Patients with Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with SARS-CoV-2 and Hyperinflammation in COVID-19

Minimally invasive surgery (MIS) is associated with a higher risk for death in comparison to open surgery for patients with gynecologic cancers, according to two new reports.

In the first study, use of MIS for patients with early-stage ovarian cancer was associated with an increased risk for capsule rupture, which, in turn, led to an increase in mortality.

“There was a striking association between an increased risk of capsule rupture with use of minimally invasive surgery,” said Jason D. Wright, MD, chief, division of gynecologic oncology, Columbia University Herbert Irving Cancer Comprehensive Center, New York, who was a coauthor for both studies.

“This is certainly worrisome, as there are limited data describing the safety of minimally invasive surgery for ovarian cancer, and we noted that the use of minimally invasive procedures increased substantially,” he added.

The second article, a meta-analysis of 15 studies, found that minimally invasive radical hysterectomy was associated with a higher risk for recurrence and death in comparison to open surgery for women with early-stage cervical cancer. This confirms previous reports of worse outcomes, including a randomized trial (the LACC study) published in 2018. The results of that trial showed an increased risk for death, which was “unexpected and alarming.”

The meta-analysis confirms and “demonstrates the magnitude of this risk on recurrence rates and survival,” Dr. Wright said in an interview.

“Given these data, I think that clinicians should use great caution in performing this procedure and that the majority of women with cervical cancer who undergo radical hysterectomy should likely have an open surgery,” said Dr. Wright.

Both articles were published on June 11 in JAMA Oncology.

These “two important studies add to the growing body of literature that suggest a worse outcome for patients with gynecologic cancers who are treated with MIS,” Amer Karam, MD, and Oliver Dorigo, MD, PhD, both from Stanford (Calif.) University, wrote in an accompanying editorial.
 

Ovarian cancer MIS and capsule rupture

In the study of MIS in ovarian cancer, observational data were collected on 8850 women (mean age, 55.6 years) with stage I epithelial ovarian cancer who were registered in the National Cancer Database and who underwent surgery between 2010 and 2015. Roughly one third (n = 2,600) underwent MIS; the remainder underwent open surgery.

During the 5 years of the study period, there was a 80% increase in the use of MIS, from 19.8% to 34.9% (P < .001).

The data show that 1,994 patients (22.5%) experienced capsule rupture and that the rate of rupture rose from 20.2% in 2010 to 23.9% in 2015. This extrapolates to an 18.3% relative increase (Cochran-Armitage trend test P = 0.02).

Multivariable analysis showed that MIS was independently associated with capsule rupture (adjusted relative risk, 1.17), as was larger tumor size. Additionally, receipt of chemotherapy increased the risk for rupture (unilateral tumors, 67.0% vs. 38.6%; bilateral tumors, 80.0% vs. 58.9%; P < .001).

The 4-year overall survival rate was 91% in 2010 and fell to 86% in 2015.

Among those with ruptured tumors, the 4-year overall survival was 86.8% for those who underwent open surgery and 88.9% for patients who underwent MIS.

Among women with nonruptured tumors, these rates were 90.5% and 91.5%, respectively (log-rank test, P = .001).

An adjusted model showed that the use of MIS with capsule rupture was independently associated with an increase in all-cause mortality in comparison with MIS in which capsule rupture did not occur (adjusted hazard ratio, 1.41). In addition, laparotomy with capsule rupture was also independently associated with a greater risk for all-cause mortality compared with laparotomy without capsule rupture (aHR, 1.43).

“I think clinicians need to carefully weigh the risks and benefits of minimally invasive surgery and the risk of rupture of an ovarian cancer in women, and high-quality studies are clearly needed to address this topic,” said Dr. Wright.
 

Lower survival in cervical cancer

The second study was a meta-analysis of 15 studies involving 9,499 women who underwent radical hysterectomy for stage IA1 to IIA cervical cancer.

Nearly half of the cohort (n = 4,684; 49%) underwent MIS. Of those, 57% (n = 2675) underwent robot-assisted laparoscopy.

A total of 530 recurrences and 451 deaths were reported. The pooled hazard of recurrence or death was 71% higher among patients who underwent MIS in comparison with those who underwent open surgery (HR, 1.71; P < .001). The hazard of death was 56% higher in the MIS group than in the open surgery group (HR, 1.56; P = .004).

“The magnitude of the effect, while lower than that reported in the LACC trial, is still notable and likely reflects real-world outcomes,” the editorialists said.

They also noted that the “results of the LACC trial remain controversial but were followed by a global decrease in the use of MIS for treatment of early-stage cervical cancer.”

However, the editorialists also highlighted the advantages of MIS, saying it has “considerable benefits” in the treatment of gynecologic cancer.

They cited an article from the American College of Surgeons National Quality Improvement Program, which reports an analysis of 2076 endometrial cancer cases that found a much lower complication rate after MIS compared with laparotomy (12% vs. 31%).

“Shorter hospital stays and lower complication rates could result in an estimated cost savings of $534 million if MIS was used in 90% of all patients with endometrial cancer in the U.S.A.,” they wrote.

Nevertheless, they added that “the short-term advantages of MIS for gynecologic cancers should be weighed against the risks of potentially worse long-term outcomes.”

These two latest studies should serve as another call to action, they concluded. “We owe it to patients to study any surgical or medical intervention adhering to the highest standards of clinical investigation.”

The ovarian cancer study was supported by grants from the National Cancer Institute Cancer Center and the National Institutes of Health. The cervical cancer meta-analysis study was funded by the National Cancer Institute, the American Cancer Society, and the Frank McGraw Memorial Chair in Cancer Research and Ensign Endowment for Gynecologic Cancer Research. Dr. Wright has received grants from Merck and consultation fees from Clovis Oncology outside the submitted work; several coauthors from both articles report relationships with industry. Dr. Karam has received personal fees from Clovis Oncology, AstraZeneca, GSK, and UpToDate outside the submitted work. Dr. Dorigo has received fees from many pharmaceutical companies and salary for medical legal expert witness testimony.

This article first appeared on Medscape.com.

Minimally invasive surgery (MIS) is associated with a higher risk for death in comparison to open surgery for patients with gynecologic cancers, according to two new reports.

In the first study, use of MIS for patients with early-stage ovarian cancer was associated with an increased risk for capsule rupture, which, in turn, led to an increase in mortality.

“There was a striking association between an increased risk of capsule rupture with use of minimally invasive surgery,” said Jason D. Wright, MD, chief, division of gynecologic oncology, Columbia University Herbert Irving Cancer Comprehensive Center, New York, who was a coauthor for both studies.

“This is certainly worrisome, as there are limited data describing the safety of minimally invasive surgery for ovarian cancer, and we noted that the use of minimally invasive procedures increased substantially,” he added.

The second article, a meta-analysis of 15 studies, found that minimally invasive radical hysterectomy was associated with a higher risk for recurrence and death in comparison to open surgery for women with early-stage cervical cancer. This confirms previous reports of worse outcomes, including a randomized trial (the LACC study) published in 2018. The results of that trial showed an increased risk for death, which was “unexpected and alarming.”

The meta-analysis confirms and “demonstrates the magnitude of this risk on recurrence rates and survival,” Dr. Wright said in an interview.

“Given these data, I think that clinicians should use great caution in performing this procedure and that the majority of women with cervical cancer who undergo radical hysterectomy should likely have an open surgery,” said Dr. Wright.

Both articles were published on June 11 in JAMA Oncology.

These “two important studies add to the growing body of literature that suggest a worse outcome for patients with gynecologic cancers who are treated with MIS,” Amer Karam, MD, and Oliver Dorigo, MD, PhD, both from Stanford (Calif.) University, wrote in an accompanying editorial.
 

Ovarian cancer MIS and capsule rupture

In the study of MIS in ovarian cancer, observational data were collected on 8850 women (mean age, 55.6 years) with stage I epithelial ovarian cancer who were registered in the National Cancer Database and who underwent surgery between 2010 and 2015. Roughly one third (n = 2,600) underwent MIS; the remainder underwent open surgery.

During the 5 years of the study period, there was a 80% increase in the use of MIS, from 19.8% to 34.9% (P < .001).

The data show that 1,994 patients (22.5%) experienced capsule rupture and that the rate of rupture rose from 20.2% in 2010 to 23.9% in 2015. This extrapolates to an 18.3% relative increase (Cochran-Armitage trend test P = 0.02).

Multivariable analysis showed that MIS was independently associated with capsule rupture (adjusted relative risk, 1.17), as was larger tumor size. Additionally, receipt of chemotherapy increased the risk for rupture (unilateral tumors, 67.0% vs. 38.6%; bilateral tumors, 80.0% vs. 58.9%; P < .001).

The 4-year overall survival rate was 91% in 2010 and fell to 86% in 2015.

Among those with ruptured tumors, the 4-year overall survival was 86.8% for those who underwent open surgery and 88.9% for patients who underwent MIS.

Among women with nonruptured tumors, these rates were 90.5% and 91.5%, respectively (log-rank test, P = .001).

An adjusted model showed that the use of MIS with capsule rupture was independently associated with an increase in all-cause mortality in comparison with MIS in which capsule rupture did not occur (adjusted hazard ratio, 1.41). In addition, laparotomy with capsule rupture was also independently associated with a greater risk for all-cause mortality compared with laparotomy without capsule rupture (aHR, 1.43).

“I think clinicians need to carefully weigh the risks and benefits of minimally invasive surgery and the risk of rupture of an ovarian cancer in women, and high-quality studies are clearly needed to address this topic,” said Dr. Wright.
 

Lower survival in cervical cancer

The second study was a meta-analysis of 15 studies involving 9,499 women who underwent radical hysterectomy for stage IA1 to IIA cervical cancer.

Nearly half of the cohort (n = 4,684; 49%) underwent MIS. Of those, 57% (n = 2675) underwent robot-assisted laparoscopy.

A total of 530 recurrences and 451 deaths were reported. The pooled hazard of recurrence or death was 71% higher among patients who underwent MIS in comparison with those who underwent open surgery (HR, 1.71; P < .001). The hazard of death was 56% higher in the MIS group than in the open surgery group (HR, 1.56; P = .004).

“The magnitude of the effect, while lower than that reported in the LACC trial, is still notable and likely reflects real-world outcomes,” the editorialists said.

They also noted that the “results of the LACC trial remain controversial but were followed by a global decrease in the use of MIS for treatment of early-stage cervical cancer.”

However, the editorialists also highlighted the advantages of MIS, saying it has “considerable benefits” in the treatment of gynecologic cancer.

They cited an article from the American College of Surgeons National Quality Improvement Program, which reports an analysis of 2076 endometrial cancer cases that found a much lower complication rate after MIS compared with laparotomy (12% vs. 31%).

“Shorter hospital stays and lower complication rates could result in an estimated cost savings of $534 million if MIS was used in 90% of all patients with endometrial cancer in the U.S.A.,” they wrote.

Nevertheless, they added that “the short-term advantages of MIS for gynecologic cancers should be weighed against the risks of potentially worse long-term outcomes.”

These two latest studies should serve as another call to action, they concluded. “We owe it to patients to study any surgical or medical intervention adhering to the highest standards of clinical investigation.”

The ovarian cancer study was supported by grants from the National Cancer Institute Cancer Center and the National Institutes of Health. The cervical cancer meta-analysis study was funded by the National Cancer Institute, the American Cancer Society, and the Frank McGraw Memorial Chair in Cancer Research and Ensign Endowment for Gynecologic Cancer Research. Dr. Wright has received grants from Merck and consultation fees from Clovis Oncology outside the submitted work; several coauthors from both articles report relationships with industry. Dr. Karam has received personal fees from Clovis Oncology, AstraZeneca, GSK, and UpToDate outside the submitted work. Dr. Dorigo has received fees from many pharmaceutical companies and salary for medical legal expert witness testimony.

This article first appeared on Medscape.com.

Minimally invasive surgery (MIS) is associated with a higher risk for death in comparison to open surgery for patients with gynecologic cancers, according to two new reports.

In the first study, use of MIS for patients with early-stage ovarian cancer was associated with an increased risk for capsule rupture, which, in turn, led to an increase in mortality.

“There was a striking association between an increased risk of capsule rupture with use of minimally invasive surgery,” said Jason D. Wright, MD, chief, division of gynecologic oncology, Columbia University Herbert Irving Cancer Comprehensive Center, New York, who was a coauthor for both studies.

“This is certainly worrisome, as there are limited data describing the safety of minimally invasive surgery for ovarian cancer, and we noted that the use of minimally invasive procedures increased substantially,” he added.

The second article, a meta-analysis of 15 studies, found that minimally invasive radical hysterectomy was associated with a higher risk for recurrence and death in comparison to open surgery for women with early-stage cervical cancer. This confirms previous reports of worse outcomes, including a randomized trial (the LACC study) published in 2018. The results of that trial showed an increased risk for death, which was “unexpected and alarming.”

The meta-analysis confirms and “demonstrates the magnitude of this risk on recurrence rates and survival,” Dr. Wright said in an interview.

“Given these data, I think that clinicians should use great caution in performing this procedure and that the majority of women with cervical cancer who undergo radical hysterectomy should likely have an open surgery,” said Dr. Wright.

Both articles were published on June 11 in JAMA Oncology.

These “two important studies add to the growing body of literature that suggest a worse outcome for patients with gynecologic cancers who are treated with MIS,” Amer Karam, MD, and Oliver Dorigo, MD, PhD, both from Stanford (Calif.) University, wrote in an accompanying editorial.
 

Ovarian cancer MIS and capsule rupture

In the study of MIS in ovarian cancer, observational data were collected on 8850 women (mean age, 55.6 years) with stage I epithelial ovarian cancer who were registered in the National Cancer Database and who underwent surgery between 2010 and 2015. Roughly one third (n = 2,600) underwent MIS; the remainder underwent open surgery.

During the 5 years of the study period, there was a 80% increase in the use of MIS, from 19.8% to 34.9% (P < .001).

The data show that 1,994 patients (22.5%) experienced capsule rupture and that the rate of rupture rose from 20.2% in 2010 to 23.9% in 2015. This extrapolates to an 18.3% relative increase (Cochran-Armitage trend test P = 0.02).

Multivariable analysis showed that MIS was independently associated with capsule rupture (adjusted relative risk, 1.17), as was larger tumor size. Additionally, receipt of chemotherapy increased the risk for rupture (unilateral tumors, 67.0% vs. 38.6%; bilateral tumors, 80.0% vs. 58.9%; P < .001).

The 4-year overall survival rate was 91% in 2010 and fell to 86% in 2015.

Among those with ruptured tumors, the 4-year overall survival was 86.8% for those who underwent open surgery and 88.9% for patients who underwent MIS.

Among women with nonruptured tumors, these rates were 90.5% and 91.5%, respectively (log-rank test, P = .001).

An adjusted model showed that the use of MIS with capsule rupture was independently associated with an increase in all-cause mortality in comparison with MIS in which capsule rupture did not occur (adjusted hazard ratio, 1.41). In addition, laparotomy with capsule rupture was also independently associated with a greater risk for all-cause mortality compared with laparotomy without capsule rupture (aHR, 1.43).

“I think clinicians need to carefully weigh the risks and benefits of minimally invasive surgery and the risk of rupture of an ovarian cancer in women, and high-quality studies are clearly needed to address this topic,” said Dr. Wright.
 

Lower survival in cervical cancer

The second study was a meta-analysis of 15 studies involving 9,499 women who underwent radical hysterectomy for stage IA1 to IIA cervical cancer.

Nearly half of the cohort (n = 4,684; 49%) underwent MIS. Of those, 57% (n = 2675) underwent robot-assisted laparoscopy.

A total of 530 recurrences and 451 deaths were reported. The pooled hazard of recurrence or death was 71% higher among patients who underwent MIS in comparison with those who underwent open surgery (HR, 1.71; P < .001). The hazard of death was 56% higher in the MIS group than in the open surgery group (HR, 1.56; P = .004).

“The magnitude of the effect, while lower than that reported in the LACC trial, is still notable and likely reflects real-world outcomes,” the editorialists said.

They also noted that the “results of the LACC trial remain controversial but were followed by a global decrease in the use of MIS for treatment of early-stage cervical cancer.”

However, the editorialists also highlighted the advantages of MIS, saying it has “considerable benefits” in the treatment of gynecologic cancer.

They cited an article from the American College of Surgeons National Quality Improvement Program, which reports an analysis of 2076 endometrial cancer cases that found a much lower complication rate after MIS compared with laparotomy (12% vs. 31%).

“Shorter hospital stays and lower complication rates could result in an estimated cost savings of $534 million if MIS was used in 90% of all patients with endometrial cancer in the U.S.A.,” they wrote.

Nevertheless, they added that “the short-term advantages of MIS for gynecologic cancers should be weighed against the risks of potentially worse long-term outcomes.”

These two latest studies should serve as another call to action, they concluded. “We owe it to patients to study any surgical or medical intervention adhering to the highest standards of clinical investigation.”

The ovarian cancer study was supported by grants from the National Cancer Institute Cancer Center and the National Institutes of Health. The cervical cancer meta-analysis study was funded by the National Cancer Institute, the American Cancer Society, and the Frank McGraw Memorial Chair in Cancer Research and Ensign Endowment for Gynecologic Cancer Research. Dr. Wright has received grants from Merck and consultation fees from Clovis Oncology outside the submitted work; several coauthors from both articles report relationships with industry. Dr. Karam has received personal fees from Clovis Oncology, AstraZeneca, GSK, and UpToDate outside the submitted work. Dr. Dorigo has received fees from many pharmaceutical companies and salary for medical legal expert witness testimony.

This article first appeared on Medscape.com.

The interleukin (IL)-23 inhibitor risankizumab was decisively more effective than the IL-17A inhibitor secukinumab at 52 weeks in a multinational randomized head-to-head trial in patients with moderate to severe psoriasis.

Risankizumab was better tolerated, with a significantly lower rate of treatment-emergent adverse events and a lower study dropout rate, Richard B. Warren, MBChB, PhD, reported at the virtual annual meeting of the American Academy of Dermatology.

In addition, the dosing schedule for risankizumab (Skyrizi) is more convenient, with maintenance dosing by subcutaneous injection once every 12 weeks, compared with monthly for secukinumab (Cosentyx), a biologic for psoriasis considered state-of-the-art not long ago, noted Dr. Warren, a dermatologist at the Salford (England) Royal NHS Foundation Trust and the Manchester NIHR Biomedical Research Center as well as professor of dermatology at the University of Manchester.

The phase 3 IMMERGE trial included 327 patients with moderate to severe psoriasis randomized to risankizumab or secukinumab for 52 weeks at their approved dosing. The trial, conducted mainly in the United States, Canada, and Europe, was open label, but evaluator blinded.

The coprimary endpoints were a 90% improvement from baseline in Psoriasis Area and Severity Index scores (PASI 90) at weeks 16 and 52. The week 52 PASI 90 response rates were 87% in the risankizumab group and 57% with secukinumab, for a highly significant absolute 30% difference. The week 16 result was a prespecified noninferiority analysis, and here again risankizumab met its mark, with a PASI 90 rate of 74%, statistically noninferior to the 66% rate with secukinumab, even though at that point patients had received only two doses of risankizumab, versus seven doses of secukinumab.

The PASI 100 response rate at 52 weeks, a key secondary endpoint, was 66% with risankizumab and 40% with secukinumab. Another secondary endpoint was achievement of a static Physician Global Assessment score of 0 or 1 – clear or almost clear – at week 52; the rates were 88% with risankizumab, 58% with secukinumab.

Ninety-two percent of participants randomized to risankizumab completed the full 52-week study, as did 82.8% of the secukinumab group. The nearly 10% absolute lower completion rate in the secukinumab group was driven by a higher rate of lack of efficacy – 4.3%, compared to 0.6% for risankizumab – and a greater incidence of adverse events. Indeed, treatment-emergent adverse events were fourfold more common in the secukinumab arm, with a rate of 4.9%, versus 1.2% with risankizumab, according to Dr. Warren.

He reported receiving research grants from and serving as a consultant to the study sponsor, AbbVie, as well as roughly a dozen other pharmaceutical companies.

[email protected]

The interleukin (IL)-23 inhibitor risankizumab was decisively more effective than the IL-17A inhibitor secukinumab at 52 weeks in a multinational randomized head-to-head trial in patients with moderate to severe psoriasis.

Risankizumab was better tolerated, with a significantly lower rate of treatment-emergent adverse events and a lower study dropout rate, Richard B. Warren, MBChB, PhD, reported at the virtual annual meeting of the American Academy of Dermatology.

In addition, the dosing schedule for risankizumab (Skyrizi) is more convenient, with maintenance dosing by subcutaneous injection once every 12 weeks, compared with monthly for secukinumab (Cosentyx), a biologic for psoriasis considered state-of-the-art not long ago, noted Dr. Warren, a dermatologist at the Salford (England) Royal NHS Foundation Trust and the Manchester NIHR Biomedical Research Center as well as professor of dermatology at the University of Manchester.

The phase 3 IMMERGE trial included 327 patients with moderate to severe psoriasis randomized to risankizumab or secukinumab for 52 weeks at their approved dosing. The trial, conducted mainly in the United States, Canada, and Europe, was open label, but evaluator blinded.

The coprimary endpoints were a 90% improvement from baseline in Psoriasis Area and Severity Index scores (PASI 90) at weeks 16 and 52. The week 52 PASI 90 response rates were 87% in the risankizumab group and 57% with secukinumab, for a highly significant absolute 30% difference. The week 16 result was a prespecified noninferiority analysis, and here again risankizumab met its mark, with a PASI 90 rate of 74%, statistically noninferior to the 66% rate with secukinumab, even though at that point patients had received only two doses of risankizumab, versus seven doses of secukinumab.

The PASI 100 response rate at 52 weeks, a key secondary endpoint, was 66% with risankizumab and 40% with secukinumab. Another secondary endpoint was achievement of a static Physician Global Assessment score of 0 or 1 – clear or almost clear – at week 52; the rates were 88% with risankizumab, 58% with secukinumab.

Ninety-two percent of participants randomized to risankizumab completed the full 52-week study, as did 82.8% of the secukinumab group. The nearly 10% absolute lower completion rate in the secukinumab group was driven by a higher rate of lack of efficacy – 4.3%, compared to 0.6% for risankizumab – and a greater incidence of adverse events. Indeed, treatment-emergent adverse events were fourfold more common in the secukinumab arm, with a rate of 4.9%, versus 1.2% with risankizumab, according to Dr. Warren.

He reported receiving research grants from and serving as a consultant to the study sponsor, AbbVie, as well as roughly a dozen other pharmaceutical companies.

[email protected]

The interleukin (IL)-23 inhibitor risankizumab was decisively more effective than the IL-17A inhibitor secukinumab at 52 weeks in a multinational randomized head-to-head trial in patients with moderate to severe psoriasis.

Risankizumab was better tolerated, with a significantly lower rate of treatment-emergent adverse events and a lower study dropout rate, Richard B. Warren, MBChB, PhD, reported at the virtual annual meeting of the American Academy of Dermatology.

In addition, the dosing schedule for risankizumab (Skyrizi) is more convenient, with maintenance dosing by subcutaneous injection once every 12 weeks, compared with monthly for secukinumab (Cosentyx), a biologic for psoriasis considered state-of-the-art not long ago, noted Dr. Warren, a dermatologist at the Salford (England) Royal NHS Foundation Trust and the Manchester NIHR Biomedical Research Center as well as professor of dermatology at the University of Manchester.

The phase 3 IMMERGE trial included 327 patients with moderate to severe psoriasis randomized to risankizumab or secukinumab for 52 weeks at their approved dosing. The trial, conducted mainly in the United States, Canada, and Europe, was open label, but evaluator blinded.

The coprimary endpoints were a 90% improvement from baseline in Psoriasis Area and Severity Index scores (PASI 90) at weeks 16 and 52. The week 52 PASI 90 response rates were 87% in the risankizumab group and 57% with secukinumab, for a highly significant absolute 30% difference. The week 16 result was a prespecified noninferiority analysis, and here again risankizumab met its mark, with a PASI 90 rate of 74%, statistically noninferior to the 66% rate with secukinumab, even though at that point patients had received only two doses of risankizumab, versus seven doses of secukinumab.

The PASI 100 response rate at 52 weeks, a key secondary endpoint, was 66% with risankizumab and 40% with secukinumab. Another secondary endpoint was achievement of a static Physician Global Assessment score of 0 or 1 – clear or almost clear – at week 52; the rates were 88% with risankizumab, 58% with secukinumab.

Ninety-two percent of participants randomized to risankizumab completed the full 52-week study, as did 82.8% of the secukinumab group. The nearly 10% absolute lower completion rate in the secukinumab group was driven by a higher rate of lack of efficacy – 4.3%, compared to 0.6% for risankizumab – and a greater incidence of adverse events. Indeed, treatment-emergent adverse events were fourfold more common in the secukinumab arm, with a rate of 4.9%, versus 1.2% with risankizumab, according to Dr. Warren.

He reported receiving research grants from and serving as a consultant to the study sponsor, AbbVie, as well as roughly a dozen other pharmaceutical companies.

[email protected]

Adults with prediabetes of normal weight may derive at least as much benefit from lifestyle health coaching programs as adults who are overweight or obese, results of a recent nonrandomized, real-world study show.

Fasting plasma glucose (FPG) normalized in about 63% of prediabetic adults with normal body mass index (BMI) participating in a personalized coaching program that emphasized exercise, nutrition, and weight management, according to researcher Mandy Salmon, MS.

By contrast, FPG normalized in about 52% of overweight and 44% of obese prediabetic individuals participating in the program, according to Ms. Salmon, a medical student at the University of Pennsylvania, Philadelphia.

The normal-weight individuals didn’t lose any weight after participating in the coaching program, but they did significantly increase exercise, as did their overweight and obese counterparts, Ms. Salmon said in a presentation of her findings at virtual annual scientific sessions of the American Diabetes Association.

That means not only that normal-weight individuals shouldn’t be excluded from coaching interventions for diabetes prevention, but also that the success of such programs shouldn’t be judged solely on the magnitude of weight loss, according to the researcher.

“It is interesting to note that, although the normal weight group lost the least amount of weight, they still benefited from the lifestyle health coaching program, but having a resultant greatest decrease in fasting plasma glucose and normalization to a range of someone without prediabetes,” Ms. Salmon said.

The fact that most of those patients experienced normalization of FPG despite no weight loss emphasizes the importance of physical activity as a lifestyle intervention, according to Mark Schutta, MD, medical director of Penn Rodebaugh Diabetes Center in Philadelphia, who was not involved in the study.

“You hear these axioms that say things like, ‘you can never outexercise a bad diet,’ and that’s probably true. But all the studies will tell us that a fit, overweight diabetic has much lower risk of cardiovascular disease than an unfit overweight diabetic,” Dr. Schutta said in an interview.
 

Benefits in normal-weight individuals

One in three Americans has prediabetes, and of those individuals, one in five have a normal BMI, Ms. Salmon said in her virtual ADA presentation.

It’s thought that diabetes may develop in those normal-weight individuals through different pathological mechanisms than in overweight or obese individuals. In turn, that could mean that standard methods for staving off diabetes prevention may not be as effective for them, she said.

Those mechanisms are not well understood; even so, normal BMI is currently an exclusion criterion for many diabetes prevention programs, she added, including the Center for Disease Control and Prevention’s National Diabetes Prevention Program, which specifically requires that individuals have an elevated BMI to be eligible for referral.

To evaluate the potential benefits of coaching in normal-weight individuals, the investigators studied a cohort of 1,897 adults with prediabetes, defined as a baseline FPG of 100-125 mg/dL, who were participating in a lifestyle health coaching program. Of those participants, 188, or about 10% had a normal BMI of 18.5-24.9 mg/m². Another 495 participants were overweight, with BMIs between 25 and 29.9, while 1,214 were obese, with a BMI of at least 30.

The intervention included an initial assessment to generate goals and a personalized action plan based on the individual’s risk factors, according to Ms. Salmon, along with an action plan that included one-on-one, behaviorally oriented, technology-enabled lifestyle health coaching focused on exercise and physical activity, weight management, and nutrition.
 

Key findings

With a mean follow-up of 145 days, weight loss in the obese group was greater than that of the overweight group, with mean BMI changes of –1.3 and –0.6, respectively, while there was no significant change in weight for the normal-weight individuals, according to Ms. Salmon.

By contrast, weekly aerobic activity increased significantly in all three groups, she added, with average increases of 95 minutes in the obese group, 98 minutes in the overweight group, and 77 minutes in the normal-weight group.

Likewise, significant decreases in FPG were seen in all 3 groups, with average changes of –6 mg/dL for the obese participants, –7 mg/dL for overweight participants, and –9 mg/dL for normal-weight participants, Ms. Salmon said.

The proportion of individuals whose FPG normalized was highest in the normal-weight group, at 62%, compared with 51.7% for overweight and 44% for obese individuals, she added.

Most previous studies of lifestyle interventions for prediabetes have excluded normal-weight individuals, according to Ms. Salmon, who said one strength of her study was that the subjects were already participating in the established lifestyle health coaching program and didn’t interact with the team of researchers.

“It was an effectiveness study in which we could see the real-world benefits of the program, rather than a theoretical efficacy study,” she said.

Ms. Salmon said she had no potential conflicts of interest to disclose. The coinvestigators of the study were members or employees of a privately held population health management company called INTERVENT International.

SOURCE: Salmon MK et al. ADA 2020, Abstract 273-OR.

Adults with prediabetes of normal weight may derive at least as much benefit from lifestyle health coaching programs as adults who are overweight or obese, results of a recent nonrandomized, real-world study show.

Fasting plasma glucose (FPG) normalized in about 63% of prediabetic adults with normal body mass index (BMI) participating in a personalized coaching program that emphasized exercise, nutrition, and weight management, according to researcher Mandy Salmon, MS.

By contrast, FPG normalized in about 52% of overweight and 44% of obese prediabetic individuals participating in the program, according to Ms. Salmon, a medical student at the University of Pennsylvania, Philadelphia.

The normal-weight individuals didn’t lose any weight after participating in the coaching program, but they did significantly increase exercise, as did their overweight and obese counterparts, Ms. Salmon said in a presentation of her findings at virtual annual scientific sessions of the American Diabetes Association.

That means not only that normal-weight individuals shouldn’t be excluded from coaching interventions for diabetes prevention, but also that the success of such programs shouldn’t be judged solely on the magnitude of weight loss, according to the researcher.

“It is interesting to note that, although the normal weight group lost the least amount of weight, they still benefited from the lifestyle health coaching program, but having a resultant greatest decrease in fasting plasma glucose and normalization to a range of someone without prediabetes,” Ms. Salmon said.

The fact that most of those patients experienced normalization of FPG despite no weight loss emphasizes the importance of physical activity as a lifestyle intervention, according to Mark Schutta, MD, medical director of Penn Rodebaugh Diabetes Center in Philadelphia, who was not involved in the study.

“You hear these axioms that say things like, ‘you can never outexercise a bad diet,’ and that’s probably true. But all the studies will tell us that a fit, overweight diabetic has much lower risk of cardiovascular disease than an unfit overweight diabetic,” Dr. Schutta said in an interview.
 

Benefits in normal-weight individuals

One in three Americans has prediabetes, and of those individuals, one in five have a normal BMI, Ms. Salmon said in her virtual ADA presentation.

It’s thought that diabetes may develop in those normal-weight individuals through different pathological mechanisms than in overweight or obese individuals. In turn, that could mean that standard methods for staving off diabetes prevention may not be as effective for them, she said.

Those mechanisms are not well understood; even so, normal BMI is currently an exclusion criterion for many diabetes prevention programs, she added, including the Center for Disease Control and Prevention’s National Diabetes Prevention Program, which specifically requires that individuals have an elevated BMI to be eligible for referral.

To evaluate the potential benefits of coaching in normal-weight individuals, the investigators studied a cohort of 1,897 adults with prediabetes, defined as a baseline FPG of 100-125 mg/dL, who were participating in a lifestyle health coaching program. Of those participants, 188, or about 10% had a normal BMI of 18.5-24.9 mg/m². Another 495 participants were overweight, with BMIs between 25 and 29.9, while 1,214 were obese, with a BMI of at least 30.

The intervention included an initial assessment to generate goals and a personalized action plan based on the individual’s risk factors, according to Ms. Salmon, along with an action plan that included one-on-one, behaviorally oriented, technology-enabled lifestyle health coaching focused on exercise and physical activity, weight management, and nutrition.
 

Key findings

With a mean follow-up of 145 days, weight loss in the obese group was greater than that of the overweight group, with mean BMI changes of –1.3 and –0.6, respectively, while there was no significant change in weight for the normal-weight individuals, according to Ms. Salmon.

By contrast, weekly aerobic activity increased significantly in all three groups, she added, with average increases of 95 minutes in the obese group, 98 minutes in the overweight group, and 77 minutes in the normal-weight group.

Likewise, significant decreases in FPG were seen in all 3 groups, with average changes of –6 mg/dL for the obese participants, –7 mg/dL for overweight participants, and –9 mg/dL for normal-weight participants, Ms. Salmon said.

The proportion of individuals whose FPG normalized was highest in the normal-weight group, at 62%, compared with 51.7% for overweight and 44% for obese individuals, she added.

Most previous studies of lifestyle interventions for prediabetes have excluded normal-weight individuals, according to Ms. Salmon, who said one strength of her study was that the subjects were already participating in the established lifestyle health coaching program and didn’t interact with the team of researchers.

“It was an effectiveness study in which we could see the real-world benefits of the program, rather than a theoretical efficacy study,” she said.

Ms. Salmon said she had no potential conflicts of interest to disclose. The coinvestigators of the study were members or employees of a privately held population health management company called INTERVENT International.

SOURCE: Salmon MK et al. ADA 2020, Abstract 273-OR.

Adults with prediabetes of normal weight may derive at least as much benefit from lifestyle health coaching programs as adults who are overweight or obese, results of a recent nonrandomized, real-world study show.

Fasting plasma glucose (FPG) normalized in about 63% of prediabetic adults with normal body mass index (BMI) participating in a personalized coaching program that emphasized exercise, nutrition, and weight management, according to researcher Mandy Salmon, MS.

By contrast, FPG normalized in about 52% of overweight and 44% of obese prediabetic individuals participating in the program, according to Ms. Salmon, a medical student at the University of Pennsylvania, Philadelphia.

The normal-weight individuals didn’t lose any weight after participating in the coaching program, but they did significantly increase exercise, as did their overweight and obese counterparts, Ms. Salmon said in a presentation of her findings at virtual annual scientific sessions of the American Diabetes Association.

That means not only that normal-weight individuals shouldn’t be excluded from coaching interventions for diabetes prevention, but also that the success of such programs shouldn’t be judged solely on the magnitude of weight loss, according to the researcher.

“It is interesting to note that, although the normal weight group lost the least amount of weight, they still benefited from the lifestyle health coaching program, but having a resultant greatest decrease in fasting plasma glucose and normalization to a range of someone without prediabetes,” Ms. Salmon said.

The fact that most of those patients experienced normalization of FPG despite no weight loss emphasizes the importance of physical activity as a lifestyle intervention, according to Mark Schutta, MD, medical director of Penn Rodebaugh Diabetes Center in Philadelphia, who was not involved in the study.

“You hear these axioms that say things like, ‘you can never outexercise a bad diet,’ and that’s probably true. But all the studies will tell us that a fit, overweight diabetic has much lower risk of cardiovascular disease than an unfit overweight diabetic,” Dr. Schutta said in an interview.
 

Benefits in normal-weight individuals

One in three Americans has prediabetes, and of those individuals, one in five have a normal BMI, Ms. Salmon said in her virtual ADA presentation.

It’s thought that diabetes may develop in those normal-weight individuals through different pathological mechanisms than in overweight or obese individuals. In turn, that could mean that standard methods for staving off diabetes prevention may not be as effective for them, she said.

Those mechanisms are not well understood; even so, normal BMI is currently an exclusion criterion for many diabetes prevention programs, she added, including the Center for Disease Control and Prevention’s National Diabetes Prevention Program, which specifically requires that individuals have an elevated BMI to be eligible for referral.

To evaluate the potential benefits of coaching in normal-weight individuals, the investigators studied a cohort of 1,897 adults with prediabetes, defined as a baseline FPG of 100-125 mg/dL, who were participating in a lifestyle health coaching program. Of those participants, 188, or about 10% had a normal BMI of 18.5-24.9 mg/m². Another 495 participants were overweight, with BMIs between 25 and 29.9, while 1,214 were obese, with a BMI of at least 30.

The intervention included an initial assessment to generate goals and a personalized action plan based on the individual’s risk factors, according to Ms. Salmon, along with an action plan that included one-on-one, behaviorally oriented, technology-enabled lifestyle health coaching focused on exercise and physical activity, weight management, and nutrition.
 

Key findings

With a mean follow-up of 145 days, weight loss in the obese group was greater than that of the overweight group, with mean BMI changes of –1.3 and –0.6, respectively, while there was no significant change in weight for the normal-weight individuals, according to Ms. Salmon.

By contrast, weekly aerobic activity increased significantly in all three groups, she added, with average increases of 95 minutes in the obese group, 98 minutes in the overweight group, and 77 minutes in the normal-weight group.

Likewise, significant decreases in FPG were seen in all 3 groups, with average changes of –6 mg/dL for the obese participants, –7 mg/dL for overweight participants, and –9 mg/dL for normal-weight participants, Ms. Salmon said.

The proportion of individuals whose FPG normalized was highest in the normal-weight group, at 62%, compared with 51.7% for overweight and 44% for obese individuals, she added.

Most previous studies of lifestyle interventions for prediabetes have excluded normal-weight individuals, according to Ms. Salmon, who said one strength of her study was that the subjects were already participating in the established lifestyle health coaching program and didn’t interact with the team of researchers.

“It was an effectiveness study in which we could see the real-world benefits of the program, rather than a theoretical efficacy study,” she said.

Ms. Salmon said she had no potential conflicts of interest to disclose. The coinvestigators of the study were members or employees of a privately held population health management company called INTERVENT International.

SOURCE: Salmon MK et al. ADA 2020, Abstract 273-OR.

The Food and Drug Administration has granted accelerated approval of selinexor, a nuclear transport inhibitor, for the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

Selinexor (marketed as XPOVIO by Karyopharm Therapeutics) is intended for adult patients with relapsed/refractory DLBCL, not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy, according to the FDA’s announcement.

The FDA granted selinexor accelerated approval for this indication based on the response rate seen in the SADAL trial. Continued approval for this indication “may be contingent upon verification and description of clinical benefit in confirmatory trials,” according to the FDA.

The SADAL trial (NCT02227251) was a phase 2, single-arm, open-label study of patients with DLBCL who had previously received two to five systemic regimens. The patients received selinexor at 60 mg orally on days 1 and 3 of each week.

Results in 134 patients showed an overall response rate of 29% (95% confidence interval: 22-38), with complete responses in 13% of patients. Of 39 patients who achieved a partial or complete response, 38% had a response duration of at least 6 months, and 15% had a response duration of at least 12 months, according to the FDA announcement.

The most common adverse reactions in this trial were fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3-4 laboratory abnormalities occurred in 15% or more of the patients, and comprised thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia.

Serious adverse reactions occurred in 46% of patients, most often from infection. Gastrointestinal toxicity occurred in 80% of patients, and any-grade hyponatremia occurred in 61%. Central neurological adverse reactions occurred in 25% of patients, including dizziness and mental status changes, according to the announcement.

Warnings and precautions for adverse events – including thrombocytopenia, neutropenia, gastrointestinal toxicity, hyponatremia, serious infection, neurological toxicity, and embryo-fetal toxicity – are provided in the prescribing information.

Selinexor acts through the inhibition of exportin-1 and leads to an accumulation of tumor suppressor proteins, a reduction in oncoproteins, and apoptosis of cancer cells. The drug was previously approved in 2019 for the treatment of relapsed/refractory multiple myeloma.

The SADAL trial was sponsored by Karyopharm Therapeutics.

[email protected]

SOURCE: U.S. Food and Drug Administration. 2020. Approval announcement.

The Food and Drug Administration has granted accelerated approval of selinexor, a nuclear transport inhibitor, for the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

Selinexor (marketed as XPOVIO by Karyopharm Therapeutics) is intended for adult patients with relapsed/refractory DLBCL, not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy, according to the FDA’s announcement.

The FDA granted selinexor accelerated approval for this indication based on the response rate seen in the SADAL trial. Continued approval for this indication “may be contingent upon verification and description of clinical benefit in confirmatory trials,” according to the FDA.

The SADAL trial (NCT02227251) was a phase 2, single-arm, open-label study of patients with DLBCL who had previously received two to five systemic regimens. The patients received selinexor at 60 mg orally on days 1 and 3 of each week.

Results in 134 patients showed an overall response rate of 29% (95% confidence interval: 22-38), with complete responses in 13% of patients. Of 39 patients who achieved a partial or complete response, 38% had a response duration of at least 6 months, and 15% had a response duration of at least 12 months, according to the FDA announcement.

The most common adverse reactions in this trial were fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3-4 laboratory abnormalities occurred in 15% or more of the patients, and comprised thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia.

Serious adverse reactions occurred in 46% of patients, most often from infection. Gastrointestinal toxicity occurred in 80% of patients, and any-grade hyponatremia occurred in 61%. Central neurological adverse reactions occurred in 25% of patients, including dizziness and mental status changes, according to the announcement.

Warnings and precautions for adverse events – including thrombocytopenia, neutropenia, gastrointestinal toxicity, hyponatremia, serious infection, neurological toxicity, and embryo-fetal toxicity – are provided in the prescribing information.

Selinexor acts through the inhibition of exportin-1 and leads to an accumulation of tumor suppressor proteins, a reduction in oncoproteins, and apoptosis of cancer cells. The drug was previously approved in 2019 for the treatment of relapsed/refractory multiple myeloma.

The SADAL trial was sponsored by Karyopharm Therapeutics.

[email protected]

SOURCE: U.S. Food and Drug Administration. 2020. Approval announcement.

The Food and Drug Administration has granted accelerated approval of selinexor, a nuclear transport inhibitor, for the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

Selinexor (marketed as XPOVIO by Karyopharm Therapeutics) is intended for adult patients with relapsed/refractory DLBCL, not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy, according to the FDA’s announcement.

The FDA granted selinexor accelerated approval for this indication based on the response rate seen in the SADAL trial. Continued approval for this indication “may be contingent upon verification and description of clinical benefit in confirmatory trials,” according to the FDA.

The SADAL trial (NCT02227251) was a phase 2, single-arm, open-label study of patients with DLBCL who had previously received two to five systemic regimens. The patients received selinexor at 60 mg orally on days 1 and 3 of each week.

Results in 134 patients showed an overall response rate of 29% (95% confidence interval: 22-38), with complete responses in 13% of patients. Of 39 patients who achieved a partial or complete response, 38% had a response duration of at least 6 months, and 15% had a response duration of at least 12 months, according to the FDA announcement.

The most common adverse reactions in this trial were fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3-4 laboratory abnormalities occurred in 15% or more of the patients, and comprised thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia.

Serious adverse reactions occurred in 46% of patients, most often from infection. Gastrointestinal toxicity occurred in 80% of patients, and any-grade hyponatremia occurred in 61%. Central neurological adverse reactions occurred in 25% of patients, including dizziness and mental status changes, according to the announcement.

Warnings and precautions for adverse events – including thrombocytopenia, neutropenia, gastrointestinal toxicity, hyponatremia, serious infection, neurological toxicity, and embryo-fetal toxicity – are provided in the prescribing information.

Selinexor acts through the inhibition of exportin-1 and leads to an accumulation of tumor suppressor proteins, a reduction in oncoproteins, and apoptosis of cancer cells. The drug was previously approved in 2019 for the treatment of relapsed/refractory multiple myeloma.

The SADAL trial was sponsored by Karyopharm Therapeutics.

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SOURCE: U.S. Food and Drug Administration. 2020. Approval announcement.