Federal Practitioner

If budesonide-formoterol were to become available over the counter (OTC) and used as-needed for mild asthma, it would save lives and cut health care costs, according to a computer modeling study presented at the American Academy of Allergy, Asthma, and Immunology 2023 annual meeting in San Antonio.

Asthma affects 25 million people, about 1 in 13, in the United States. About 28% are uninsured or underinsured, and 70% have mild asthma. Many are using a $30 inhaled epinephrine product (Primatene Mist) – the only FDA-approved asthma inhaler available without a prescription, said Marcus Shaker, MD, MS, professor of pediatrics and medicine at Geisel School of Medicine at Dartmouth, and clinician at Dartmouth Health Children’s, N.H.

A new version of Primatene Mist was reintroduced on the market in 2018 after the product was pulled for containing chlorofluorocarbons in 2011, but it is not recommended by professional medical societies because of safety concerns over epinephrine’s adverse effects, such as increased heart rate and blood pressure.

Drugs in its class (bronchodilators) have long been associated with a higher risk for death or near-death.

Meanwhile, research more than 2 decades ago linked regular use of low-dose inhaled corticosteroids with reduced risk for asthma death.

More recently, two large studies (SYGMA 1 and SYGMA 2) compared maintenance therapy with a low-dose inhaled corticosteroid (budesonide) vs. on-demand treatment with an inhaler containing both a corticosteroid (budesonide) and a long-acting bronchodilator (formoterol).

“Using as-needed budesonide-formoterol led to outcomes that are almost as good as taking a maintenance budesonide dose every day,” said Dr. Shaker.

The Global Initiative for Asthma guidelines now recommend this approach – as-needed inhaled corticosteroids (ICS) plus long-acting bronchodilators – for adults with mild asthma. In the United States, however, the National Heart, Lung, and Blood Institute still suggests daily ICS plus quick-relief therapy as needed.

Dr. Shaker and colleagues used computer modeling to compare the cost-effectiveness of as-needed budesonide-formoterol vs. over-the-counter inhaled epinephrine in underinsured U.S. adults who were self-managing their mild asthma. The study randomly assigned these individuals into three groups: OTC inhaled epinephrine (current reality), OTC budesonide-formoterol (not yet available), or no OTC option. The model assumed that patients treated for an exacerbation were referred to a health care provider and started a regimen of ICS plus as-needed rescue therapy.

In this analysis, which has been submitted for publication, the OTC budesonide-formoterol strategy was associated with 12,495 fewer deaths, prevented nearly 14 million severe asthma exacerbations, and saved more than $68 billion. And “when we looked at OTC budesonide-formoterol vs. having no OTC option at all, budesonide-formoterol was similarly cost-effective,” said Dr. Shaker, who presented the results at an AAAAI oral abstract session.

The cost savings emerged even though in the United States asthma controller therapies (for example, fluticasone) cost about 10 times more than rescue therapies (for instance, salbutamol, OTC epinephrine).

Nevertheless, the results make sense. “If you’re using Primatene Mist, your health costs are predicted to be much greater because you’re going to be in the hospital more. Your asthma is not going to be well-controlled,” Thanai Pongdee, MD, an allergist-immunologist with the Mayo Clinic in Rochester, Minn., told this news organization. “It’s not only the cost of your ER visit but also the cost of loss of work or school, and loss of daily productivity. There are all these associated costs.”

The analysis “is certainly something policy makers could take a look at,” he said.

He noted that current use of budesonide-formoterol is stymied by difficulties with insurance coverage. The difficulties stem from a mismatch between the updated recommendation for as-needed use and the description printed on the brand-name product (Symbicort).

“On the product label, it says Symbicort should be used on a daily basis,” Dr. Pongdee said. “But if a prescription comes through and says you’re going to use this ‘as needed,’ the health plan may say that’s not appropriate because that’s not on the product label.”

Given these access challenges with the all-in-one inhaler, other researchers have developed a workaround – asking patients to continue their usual care (that is, using a rescue inhaler as needed) but to also administer a controller medication after each rescue. When tested in Black and Latino patients with moderate to severe asthma, this easy strategy (patient activated reliever-triggered inhaled corticosteroid, or PARTICS) reduced severe asthma exacerbations about as well as the all-in-one inhaler.

If the all-in-one budesonide-formoterol does become available OTC, Dr. Shaker stressed that it “would not be a substitute for seeing an allergist and getting appropriate medical care and an evaluation and all the rest. But it’s better than the status quo. It’s the sort of thing where the perfect is not the enemy of the good,” he said.

Dr. Shaker is the AAAAI cochair of the Joint Task Force on Practice Parameters and serves as an editorial board member of the Journal of Allergy and Clinical Immunology in Practice. He is also an associate editor of the Annals of Allergy, Asthma, and Immunology. Dr. Pongdee serves as an at-large director on the AAAAI board of directors. He receives grant funding from GlaxoSmithKline, and Mayo Clinic is a trial site for GlaxoSmithKline and AstraZeneca.

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

If budesonide-formoterol were to become available over the counter (OTC) and used as-needed for mild asthma, it would save lives and cut health care costs, according to a computer modeling study presented at the American Academy of Allergy, Asthma, and Immunology 2023 annual meeting in San Antonio.

Asthma affects 25 million people, about 1 in 13, in the United States. About 28% are uninsured or underinsured, and 70% have mild asthma. Many are using a $30 inhaled epinephrine product (Primatene Mist) – the only FDA-approved asthma inhaler available without a prescription, said Marcus Shaker, MD, MS, professor of pediatrics and medicine at Geisel School of Medicine at Dartmouth, and clinician at Dartmouth Health Children’s, N.H.

A new version of Primatene Mist was reintroduced on the market in 2018 after the product was pulled for containing chlorofluorocarbons in 2011, but it is not recommended by professional medical societies because of safety concerns over epinephrine’s adverse effects, such as increased heart rate and blood pressure.

Drugs in its class (bronchodilators) have long been associated with a higher risk for death or near-death.

Meanwhile, research more than 2 decades ago linked regular use of low-dose inhaled corticosteroids with reduced risk for asthma death.

More recently, two large studies (SYGMA 1 and SYGMA 2) compared maintenance therapy with a low-dose inhaled corticosteroid (budesonide) vs. on-demand treatment with an inhaler containing both a corticosteroid (budesonide) and a long-acting bronchodilator (formoterol).

“Using as-needed budesonide-formoterol led to outcomes that are almost as good as taking a maintenance budesonide dose every day,” said Dr. Shaker.

The Global Initiative for Asthma guidelines now recommend this approach – as-needed inhaled corticosteroids (ICS) plus long-acting bronchodilators – for adults with mild asthma. In the United States, however, the National Heart, Lung, and Blood Institute still suggests daily ICS plus quick-relief therapy as needed.

Dr. Shaker and colleagues used computer modeling to compare the cost-effectiveness of as-needed budesonide-formoterol vs. over-the-counter inhaled epinephrine in underinsured U.S. adults who were self-managing their mild asthma. The study randomly assigned these individuals into three groups: OTC inhaled epinephrine (current reality), OTC budesonide-formoterol (not yet available), or no OTC option. The model assumed that patients treated for an exacerbation were referred to a health care provider and started a regimen of ICS plus as-needed rescue therapy.

In this analysis, which has been submitted for publication, the OTC budesonide-formoterol strategy was associated with 12,495 fewer deaths, prevented nearly 14 million severe asthma exacerbations, and saved more than $68 billion. And “when we looked at OTC budesonide-formoterol vs. having no OTC option at all, budesonide-formoterol was similarly cost-effective,” said Dr. Shaker, who presented the results at an AAAAI oral abstract session.

The cost savings emerged even though in the United States asthma controller therapies (for example, fluticasone) cost about 10 times more than rescue therapies (for instance, salbutamol, OTC epinephrine).

Nevertheless, the results make sense. “If you’re using Primatene Mist, your health costs are predicted to be much greater because you’re going to be in the hospital more. Your asthma is not going to be well-controlled,” Thanai Pongdee, MD, an allergist-immunologist with the Mayo Clinic in Rochester, Minn., told this news organization. “It’s not only the cost of your ER visit but also the cost of loss of work or school, and loss of daily productivity. There are all these associated costs.”

The analysis “is certainly something policy makers could take a look at,” he said.

He noted that current use of budesonide-formoterol is stymied by difficulties with insurance coverage. The difficulties stem from a mismatch between the updated recommendation for as-needed use and the description printed on the brand-name product (Symbicort).

“On the product label, it says Symbicort should be used on a daily basis,” Dr. Pongdee said. “But if a prescription comes through and says you’re going to use this ‘as needed,’ the health plan may say that’s not appropriate because that’s not on the product label.”

Given these access challenges with the all-in-one inhaler, other researchers have developed a workaround – asking patients to continue their usual care (that is, using a rescue inhaler as needed) but to also administer a controller medication after each rescue. When tested in Black and Latino patients with moderate to severe asthma, this easy strategy (patient activated reliever-triggered inhaled corticosteroid, or PARTICS) reduced severe asthma exacerbations about as well as the all-in-one inhaler.

If the all-in-one budesonide-formoterol does become available OTC, Dr. Shaker stressed that it “would not be a substitute for seeing an allergist and getting appropriate medical care and an evaluation and all the rest. But it’s better than the status quo. It’s the sort of thing where the perfect is not the enemy of the good,” he said.

Dr. Shaker is the AAAAI cochair of the Joint Task Force on Practice Parameters and serves as an editorial board member of the Journal of Allergy and Clinical Immunology in Practice. He is also an associate editor of the Annals of Allergy, Asthma, and Immunology. Dr. Pongdee serves as an at-large director on the AAAAI board of directors. He receives grant funding from GlaxoSmithKline, and Mayo Clinic is a trial site for GlaxoSmithKline and AstraZeneca.

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

If budesonide-formoterol were to become available over the counter (OTC) and used as-needed for mild asthma, it would save lives and cut health care costs, according to a computer modeling study presented at the American Academy of Allergy, Asthma, and Immunology 2023 annual meeting in San Antonio.

Asthma affects 25 million people, about 1 in 13, in the United States. About 28% are uninsured or underinsured, and 70% have mild asthma. Many are using a $30 inhaled epinephrine product (Primatene Mist) – the only FDA-approved asthma inhaler available without a prescription, said Marcus Shaker, MD, MS, professor of pediatrics and medicine at Geisel School of Medicine at Dartmouth, and clinician at Dartmouth Health Children’s, N.H.

A new version of Primatene Mist was reintroduced on the market in 2018 after the product was pulled for containing chlorofluorocarbons in 2011, but it is not recommended by professional medical societies because of safety concerns over epinephrine’s adverse effects, such as increased heart rate and blood pressure.

Drugs in its class (bronchodilators) have long been associated with a higher risk for death or near-death.

Meanwhile, research more than 2 decades ago linked regular use of low-dose inhaled corticosteroids with reduced risk for asthma death.

More recently, two large studies (SYGMA 1 and SYGMA 2) compared maintenance therapy with a low-dose inhaled corticosteroid (budesonide) vs. on-demand treatment with an inhaler containing both a corticosteroid (budesonide) and a long-acting bronchodilator (formoterol).

“Using as-needed budesonide-formoterol led to outcomes that are almost as good as taking a maintenance budesonide dose every day,” said Dr. Shaker.

The Global Initiative for Asthma guidelines now recommend this approach – as-needed inhaled corticosteroids (ICS) plus long-acting bronchodilators – for adults with mild asthma. In the United States, however, the National Heart, Lung, and Blood Institute still suggests daily ICS plus quick-relief therapy as needed.

Dr. Shaker and colleagues used computer modeling to compare the cost-effectiveness of as-needed budesonide-formoterol vs. over-the-counter inhaled epinephrine in underinsured U.S. adults who were self-managing their mild asthma. The study randomly assigned these individuals into three groups: OTC inhaled epinephrine (current reality), OTC budesonide-formoterol (not yet available), or no OTC option. The model assumed that patients treated for an exacerbation were referred to a health care provider and started a regimen of ICS plus as-needed rescue therapy.

In this analysis, which has been submitted for publication, the OTC budesonide-formoterol strategy was associated with 12,495 fewer deaths, prevented nearly 14 million severe asthma exacerbations, and saved more than $68 billion. And “when we looked at OTC budesonide-formoterol vs. having no OTC option at all, budesonide-formoterol was similarly cost-effective,” said Dr. Shaker, who presented the results at an AAAAI oral abstract session.

The cost savings emerged even though in the United States asthma controller therapies (for example, fluticasone) cost about 10 times more than rescue therapies (for instance, salbutamol, OTC epinephrine).

Nevertheless, the results make sense. “If you’re using Primatene Mist, your health costs are predicted to be much greater because you’re going to be in the hospital more. Your asthma is not going to be well-controlled,” Thanai Pongdee, MD, an allergist-immunologist with the Mayo Clinic in Rochester, Minn., told this news organization. “It’s not only the cost of your ER visit but also the cost of loss of work or school, and loss of daily productivity. There are all these associated costs.”

The analysis “is certainly something policy makers could take a look at,” he said.

He noted that current use of budesonide-formoterol is stymied by difficulties with insurance coverage. The difficulties stem from a mismatch between the updated recommendation for as-needed use and the description printed on the brand-name product (Symbicort).

“On the product label, it says Symbicort should be used on a daily basis,” Dr. Pongdee said. “But if a prescription comes through and says you’re going to use this ‘as needed,’ the health plan may say that’s not appropriate because that’s not on the product label.”

Given these access challenges with the all-in-one inhaler, other researchers have developed a workaround – asking patients to continue their usual care (that is, using a rescue inhaler as needed) but to also administer a controller medication after each rescue. When tested in Black and Latino patients with moderate to severe asthma, this easy strategy (patient activated reliever-triggered inhaled corticosteroid, or PARTICS) reduced severe asthma exacerbations about as well as the all-in-one inhaler.

If the all-in-one budesonide-formoterol does become available OTC, Dr. Shaker stressed that it “would not be a substitute for seeing an allergist and getting appropriate medical care and an evaluation and all the rest. But it’s better than the status quo. It’s the sort of thing where the perfect is not the enemy of the good,” he said.

Dr. Shaker is the AAAAI cochair of the Joint Task Force on Practice Parameters and serves as an editorial board member of the Journal of Allergy and Clinical Immunology in Practice. He is also an associate editor of the Annals of Allergy, Asthma, and Immunology. Dr. Pongdee serves as an at-large director on the AAAAI board of directors. He receives grant funding from GlaxoSmithKline, and Mayo Clinic is a trial site for GlaxoSmithKline and AstraZeneca.

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

I am often asked about the impact of dietary nutrients on bone health, particularly as many patients with low bone density, many with a history of multiple fractures, are referred to me. Many factors affect bone density, an important predictor of fracture risk, including genetics, body weight and muscle mass, bone loading exercise, menstrual status, other hormonal factors, nutritional status, optimal absorption of dietary nutrients, and medication use.

Dietary nutrients include macronutrients (carbohydrates, proteins, fat, and fiber) and micronutrients (such as dietary minerals and vitamins). The importance of micronutrients such as calcium, phosphorus, magnesium, and vitamins C, D, and K in optimizing bone mineralization and bone formation has been well documented.

The impact of protein intake on bone health is slightly more controversial, with some studies suggesting that increased protein intake may be deleterious to bone by increasing acid load, which in turn, increases calcium loss in urine. Overall data analysis from multiple studies support the finding that a higher protein intake is modestly beneficial for bone at certain sites, such as the spine.

Though data regarding the impact of dietary carbohydrates on bone are not as robust, it’s important to understand these effects given the increasing knowledge of the deleterious impact of processed carbohydrates on weight and cardiometabolic outcomes. This leads to the growing recommendations to limit carbohydrates in diet.
 

Quality and quantity of carbs affect bone health

Available studies suggest that both the quality and quantity of carbohydrates that are in a diet as well as the glycemic index of food may affect bone outcomes. Glycemic index refers to the extent of blood glucose elevation that occurs after the intake of any specific food. Foods with a higher glycemic index cause a rapid increase in blood glucose, whereas those with a low glycemic index result in a slower and more gradual increase. Examples of high–glycemic index food include processed and baked foods (such as breakfast cereals [unless whole grain], pretzels, cookies, doughnuts, pastries, cake, white bread, bagels, croissants, and corn chips), sugar-sweetened beverages, white rice, fast food (such as pizza and burgers), and potatoes. Examples of low glycemic index foods include vegetables, fruits, legumes, dairy and dairy products (without added sugar), whole-grain foods (such as oat porridge), and nuts.

A high–glycemic index diet has been associated with a greater risk for obesity and cardiovascular disease, and with lower bone density, an increased risk for fracture. This has been attributed to acute increases in glucose and insulin levels after consumption of high–glycemic index food, which causes increased oxidative stress and secretion of inflammatory cytokines, such as interleukin 6 and tumor necrosis factor alpha, that activate cells in bone that increase bone loss.

Higher blood glucose concentrations induced by a higher dietary glycemic index can have deleterious effects on osteoblasts, the cells important for bone formation, and increase bone loss through production of advanced glycation end products that affect the cross linking of collagen in bone (important for bone strength), as well as calcium loss in urine. This was recently reported in a study by Garcia-Gavilan and others, in which the authors showed that high dietary glycemic index and dietary glucose load are associated with a higher risk for osteoporosis-related fractures in an older Mediterranean population who are at high risk for cardiovascular events. Similar data were reported by Nouri and coauthors in a study from Iran.

The quantity and quality of dietary carbohydrates may also have an impact on bone. The quality of carbohydrates has been assessed using the carbohydrate quality index (CQI) and the low carbohydrate diet score (LCDS). The CQI takes into account dietary fiber intake, glycemic index, intake of processed vs. whole grain, and solid vs. total carbohydrates in diet. A higher CQI diet is associated with reduced cardiovascular risk. Higher LCDS reflects lower carbohydrate and higher fat and protein intake.

Diets that are rich in refined or processed carbohydrates with added sugar are proinflammatory and increase oxidative stress, which may lead to increased bone loss, low bone density, and increased fracture risk. These foods also have a high glycemic index.

In contrast, diets that are rich in whole grains, legumes, fruits, vegetables, nuts, and olive oil have a lower glycemic index and are beneficial to bone. These diets have a higher CQI and LCDS (as reported by Nouri and coauthors) and provide a rich source of antioxidants, vitamins, minerals, and other nutrients (such as calcium, magnesium, and vitamins B, C, and K), which are all beneficial to bone. Gao and others have reported that implementing a low glycemic index pulse-based diet (lentils, peas, beans) is superior to a regular hospital diet in preventing the increase in bone loss that typically occurs during hospitalization with enforced bed rest.

Most reports of the impact of carbohydrates on bone health are from observational studies. In an interventional study, Dalskov and coauthors randomly assigned children aged 5-18 years who had parents with overweight to one of five diets (high protein/low glycemic index, high protein/high glycemic index, low protein/low glycemic index, low protein/high glycemic index, or regular) for 6 months.

Contrasting with our understanding that protein intake is overall good for bone, this study found that among patients receiving a high–glycemic index diet, those who were on a high-protein diet had greater reductions in a bone formation marker than did those on a low-protein diet, with no major changes observed with the other diets. This suggests the influence of associated dietary nutrients on bone outcomes and that protein intake may modify the effects of dietary carbohydrates on bone formation. Similarly, the fat content of food can alter the glycemic index and thus may modify the impact of dietary carbohydrates on bone.

In summary, available data suggest that the quantity and quality of carbohydrates, including the glycemic index of food, may affect bone health and that it is important to exercise moderation in the consumption of such foods. However, there are only a few studies that have examined these associations, and more studies are necessary to further clarify the impact of dietary carbohydrates on bone as well as any modifications of these effects by other associated food groups. These studies will allow us to refine our recommendations to our patients as we advance our understanding of the impact of the combined effects of various dietary nutrients on bone.

Madhusmita Misra, MD, MPH, is chief of the division of pediatric endocrinology, Mass General for Children, Boston, and serves or has served as a director, officer, partner, employee, advisor, consultant, or trustee for AbbVie, Sanofi, and Ipsen.

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

I am often asked about the impact of dietary nutrients on bone health, particularly as many patients with low bone density, many with a history of multiple fractures, are referred to me. Many factors affect bone density, an important predictor of fracture risk, including genetics, body weight and muscle mass, bone loading exercise, menstrual status, other hormonal factors, nutritional status, optimal absorption of dietary nutrients, and medication use.

Dietary nutrients include macronutrients (carbohydrates, proteins, fat, and fiber) and micronutrients (such as dietary minerals and vitamins). The importance of micronutrients such as calcium, phosphorus, magnesium, and vitamins C, D, and K in optimizing bone mineralization and bone formation has been well documented.

The impact of protein intake on bone health is slightly more controversial, with some studies suggesting that increased protein intake may be deleterious to bone by increasing acid load, which in turn, increases calcium loss in urine. Overall data analysis from multiple studies support the finding that a higher protein intake is modestly beneficial for bone at certain sites, such as the spine.

Though data regarding the impact of dietary carbohydrates on bone are not as robust, it’s important to understand these effects given the increasing knowledge of the deleterious impact of processed carbohydrates on weight and cardiometabolic outcomes. This leads to the growing recommendations to limit carbohydrates in diet.
 

Quality and quantity of carbs affect bone health

Available studies suggest that both the quality and quantity of carbohydrates that are in a diet as well as the glycemic index of food may affect bone outcomes. Glycemic index refers to the extent of blood glucose elevation that occurs after the intake of any specific food. Foods with a higher glycemic index cause a rapid increase in blood glucose, whereas those with a low glycemic index result in a slower and more gradual increase. Examples of high–glycemic index food include processed and baked foods (such as breakfast cereals [unless whole grain], pretzels, cookies, doughnuts, pastries, cake, white bread, bagels, croissants, and corn chips), sugar-sweetened beverages, white rice, fast food (such as pizza and burgers), and potatoes. Examples of low glycemic index foods include vegetables, fruits, legumes, dairy and dairy products (without added sugar), whole-grain foods (such as oat porridge), and nuts.

A high–glycemic index diet has been associated with a greater risk for obesity and cardiovascular disease, and with lower bone density, an increased risk for fracture. This has been attributed to acute increases in glucose and insulin levels after consumption of high–glycemic index food, which causes increased oxidative stress and secretion of inflammatory cytokines, such as interleukin 6 and tumor necrosis factor alpha, that activate cells in bone that increase bone loss.

Higher blood glucose concentrations induced by a higher dietary glycemic index can have deleterious effects on osteoblasts, the cells important for bone formation, and increase bone loss through production of advanced glycation end products that affect the cross linking of collagen in bone (important for bone strength), as well as calcium loss in urine. This was recently reported in a study by Garcia-Gavilan and others, in which the authors showed that high dietary glycemic index and dietary glucose load are associated with a higher risk for osteoporosis-related fractures in an older Mediterranean population who are at high risk for cardiovascular events. Similar data were reported by Nouri and coauthors in a study from Iran.

The quantity and quality of dietary carbohydrates may also have an impact on bone. The quality of carbohydrates has been assessed using the carbohydrate quality index (CQI) and the low carbohydrate diet score (LCDS). The CQI takes into account dietary fiber intake, glycemic index, intake of processed vs. whole grain, and solid vs. total carbohydrates in diet. A higher CQI diet is associated with reduced cardiovascular risk. Higher LCDS reflects lower carbohydrate and higher fat and protein intake.

Diets that are rich in refined or processed carbohydrates with added sugar are proinflammatory and increase oxidative stress, which may lead to increased bone loss, low bone density, and increased fracture risk. These foods also have a high glycemic index.

In contrast, diets that are rich in whole grains, legumes, fruits, vegetables, nuts, and olive oil have a lower glycemic index and are beneficial to bone. These diets have a higher CQI and LCDS (as reported by Nouri and coauthors) and provide a rich source of antioxidants, vitamins, minerals, and other nutrients (such as calcium, magnesium, and vitamins B, C, and K), which are all beneficial to bone. Gao and others have reported that implementing a low glycemic index pulse-based diet (lentils, peas, beans) is superior to a regular hospital diet in preventing the increase in bone loss that typically occurs during hospitalization with enforced bed rest.

Most reports of the impact of carbohydrates on bone health are from observational studies. In an interventional study, Dalskov and coauthors randomly assigned children aged 5-18 years who had parents with overweight to one of five diets (high protein/low glycemic index, high protein/high glycemic index, low protein/low glycemic index, low protein/high glycemic index, or regular) for 6 months.

Contrasting with our understanding that protein intake is overall good for bone, this study found that among patients receiving a high–glycemic index diet, those who were on a high-protein diet had greater reductions in a bone formation marker than did those on a low-protein diet, with no major changes observed with the other diets. This suggests the influence of associated dietary nutrients on bone outcomes and that protein intake may modify the effects of dietary carbohydrates on bone formation. Similarly, the fat content of food can alter the glycemic index and thus may modify the impact of dietary carbohydrates on bone.

In summary, available data suggest that the quantity and quality of carbohydrates, including the glycemic index of food, may affect bone health and that it is important to exercise moderation in the consumption of such foods. However, there are only a few studies that have examined these associations, and more studies are necessary to further clarify the impact of dietary carbohydrates on bone as well as any modifications of these effects by other associated food groups. These studies will allow us to refine our recommendations to our patients as we advance our understanding of the impact of the combined effects of various dietary nutrients on bone.

Madhusmita Misra, MD, MPH, is chief of the division of pediatric endocrinology, Mass General for Children, Boston, and serves or has served as a director, officer, partner, employee, advisor, consultant, or trustee for AbbVie, Sanofi, and Ipsen.

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

I am often asked about the impact of dietary nutrients on bone health, particularly as many patients with low bone density, many with a history of multiple fractures, are referred to me. Many factors affect bone density, an important predictor of fracture risk, including genetics, body weight and muscle mass, bone loading exercise, menstrual status, other hormonal factors, nutritional status, optimal absorption of dietary nutrients, and medication use.

Dietary nutrients include macronutrients (carbohydrates, proteins, fat, and fiber) and micronutrients (such as dietary minerals and vitamins). The importance of micronutrients such as calcium, phosphorus, magnesium, and vitamins C, D, and K in optimizing bone mineralization and bone formation has been well documented.

The impact of protein intake on bone health is slightly more controversial, with some studies suggesting that increased protein intake may be deleterious to bone by increasing acid load, which in turn, increases calcium loss in urine. Overall data analysis from multiple studies support the finding that a higher protein intake is modestly beneficial for bone at certain sites, such as the spine.

Though data regarding the impact of dietary carbohydrates on bone are not as robust, it’s important to understand these effects given the increasing knowledge of the deleterious impact of processed carbohydrates on weight and cardiometabolic outcomes. This leads to the growing recommendations to limit carbohydrates in diet.
 

Quality and quantity of carbs affect bone health

Available studies suggest that both the quality and quantity of carbohydrates that are in a diet as well as the glycemic index of food may affect bone outcomes. Glycemic index refers to the extent of blood glucose elevation that occurs after the intake of any specific food. Foods with a higher glycemic index cause a rapid increase in blood glucose, whereas those with a low glycemic index result in a slower and more gradual increase. Examples of high–glycemic index food include processed and baked foods (such as breakfast cereals [unless whole grain], pretzels, cookies, doughnuts, pastries, cake, white bread, bagels, croissants, and corn chips), sugar-sweetened beverages, white rice, fast food (such as pizza and burgers), and potatoes. Examples of low glycemic index foods include vegetables, fruits, legumes, dairy and dairy products (without added sugar), whole-grain foods (such as oat porridge), and nuts.

A high–glycemic index diet has been associated with a greater risk for obesity and cardiovascular disease, and with lower bone density, an increased risk for fracture. This has been attributed to acute increases in glucose and insulin levels after consumption of high–glycemic index food, which causes increased oxidative stress and secretion of inflammatory cytokines, such as interleukin 6 and tumor necrosis factor alpha, that activate cells in bone that increase bone loss.

Higher blood glucose concentrations induced by a higher dietary glycemic index can have deleterious effects on osteoblasts, the cells important for bone formation, and increase bone loss through production of advanced glycation end products that affect the cross linking of collagen in bone (important for bone strength), as well as calcium loss in urine. This was recently reported in a study by Garcia-Gavilan and others, in which the authors showed that high dietary glycemic index and dietary glucose load are associated with a higher risk for osteoporosis-related fractures in an older Mediterranean population who are at high risk for cardiovascular events. Similar data were reported by Nouri and coauthors in a study from Iran.

The quantity and quality of dietary carbohydrates may also have an impact on bone. The quality of carbohydrates has been assessed using the carbohydrate quality index (CQI) and the low carbohydrate diet score (LCDS). The CQI takes into account dietary fiber intake, glycemic index, intake of processed vs. whole grain, and solid vs. total carbohydrates in diet. A higher CQI diet is associated with reduced cardiovascular risk. Higher LCDS reflects lower carbohydrate and higher fat and protein intake.

Diets that are rich in refined or processed carbohydrates with added sugar are proinflammatory and increase oxidative stress, which may lead to increased bone loss, low bone density, and increased fracture risk. These foods also have a high glycemic index.

In contrast, diets that are rich in whole grains, legumes, fruits, vegetables, nuts, and olive oil have a lower glycemic index and are beneficial to bone. These diets have a higher CQI and LCDS (as reported by Nouri and coauthors) and provide a rich source of antioxidants, vitamins, minerals, and other nutrients (such as calcium, magnesium, and vitamins B, C, and K), which are all beneficial to bone. Gao and others have reported that implementing a low glycemic index pulse-based diet (lentils, peas, beans) is superior to a regular hospital diet in preventing the increase in bone loss that typically occurs during hospitalization with enforced bed rest.

Most reports of the impact of carbohydrates on bone health are from observational studies. In an interventional study, Dalskov and coauthors randomly assigned children aged 5-18 years who had parents with overweight to one of five diets (high protein/low glycemic index, high protein/high glycemic index, low protein/low glycemic index, low protein/high glycemic index, or regular) for 6 months.

Contrasting with our understanding that protein intake is overall good for bone, this study found that among patients receiving a high–glycemic index diet, those who were on a high-protein diet had greater reductions in a bone formation marker than did those on a low-protein diet, with no major changes observed with the other diets. This suggests the influence of associated dietary nutrients on bone outcomes and that protein intake may modify the effects of dietary carbohydrates on bone formation. Similarly, the fat content of food can alter the glycemic index and thus may modify the impact of dietary carbohydrates on bone.

In summary, available data suggest that the quantity and quality of carbohydrates, including the glycemic index of food, may affect bone health and that it is important to exercise moderation in the consumption of such foods. However, there are only a few studies that have examined these associations, and more studies are necessary to further clarify the impact of dietary carbohydrates on bone as well as any modifications of these effects by other associated food groups. These studies will allow us to refine our recommendations to our patients as we advance our understanding of the impact of the combined effects of various dietary nutrients on bone.

Madhusmita Misra, MD, MPH, is chief of the division of pediatric endocrinology, Mass General for Children, Boston, and serves or has served as a director, officer, partner, employee, advisor, consultant, or trustee for AbbVie, Sanofi, and Ipsen.

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

Giving pembrolizumab (Keytruda) both before and after surgery for advanced melanoma significantly improves event-free survival, show results from the phase 2 SWOG S1801 trial.

The trial involved 319 patients with operable stage IIIB to stage IV melanoma. The investigators found that patients who received pembrolizumab both before and after surgery (i.e., neoadjuvant and adjuvant therapy) fared better than those who received the drug only after surgery: The 2-year event-free survival rates were 72% vs. 49%, respectively.

The research was published in the New England Journal of Medicine, but similar results had already been presented at the European Society for Medical Oncology 2022 annual Meeting.

“It’s not just what you give; it’s when you give it,” said lead author Sapna Patel, MD, in a press release issued by the University of Texas MD Anderson Cancer Center, echoing comments she gave at ESMO 2022.

The study, she continued, “demonstrates the same treatment for resectable melanoma given before surgery can generate better outcomes.”

On the basis of their findings, Dr. Patel, who is associate professor of melanoma medical oncology at the University of Texas MD Anderson Cancer Center, Houston, said that patients with high-risk melanoma “should start immunotherapy prior to surgery to generate an immune response while the bulk of the melanoma and the anti-tumor T cells are intact.”

The mechanism of action of PD-1 blockade “relies on the presence of preexisting anti-tumor T cells attempting to attack cancer cells,” with the immunotherapy allowing the anti-tumor cells to proliferate and mediate clinical responses.

Resection of the bulk of the tumor is therefore “likely to take away some or even most of the potential anti-tumor T cells that would proliferate after PD-1 blockade,” they write.
 

Likely to apply also to nivolumab

Approached for comment, Jeffrey S. Weber, MD, PhD, professor of medicine, NYU Langone Medical Center, New York, said that outside of trials, both pembrolizumab and ipilimumab (Yervoy)/nivolumab (Opdivo) are already being used neoadjuvantly.

He thinks that the findings for neoadjuvant and adjuvant pembrolizumab could also apply to nivolumab because “the drugs are quite similar in efficacy.”

Dr. Weber told this news organization that, “even though the S1801 trial was not accepted as a registration trial by the FDA, I think that its results could very well change practice and confirm it for others who already use neoadjuvant therapy for palpable stage III melanoma.”

One question that is being addressed to an extent in the NADINA trial is whether adjuvant immunotherapy can be avoided all together and patients receive only neoadjuvant therapy, although Dr. Weber said, “I doubt that will be the case.”

Study details

In this study, patients were randomly assigned to either surgery followed by 18 doses of adjuvant pembrolizumab, or to receive 3 doses of neoadjuvant pembrolizumab followed by surgery and then 15 additional doses of adjuvant pembrolizumab.

After a median duration of follow-up of 14.7 months, there were 38 events in the neoadjuvant-adjuvant group and 67 in the adjuvant-only group.

“Events” were defined as disease progression, toxic effects, or complications that precluded surgery or the initiation of adjuvant therapy within 84 days of surgery, as well as the inability to fully resect the gross disease, melanoma recurrence, and death.

The team calculated that event-free survival was significantly longer in the neoadjuvant-adjuvant group (P = .004), with 2-year event-free survival at 72% vs. 49% in the adjuvant-only group.

“The benefit of neoadjuvant pembrolizumab was seen across all subgroups of patients,” the investigators note.

At the data cut-off, there were 14 deaths in the neoadjuvant-adjuvant group vs. 22 in the adjuvant-only group, which the researchers say is too few to allow “definitive comparison” in terms of overall survival.

Definitive surgery had been performed in 88% of neoadjuvant-adjuvant patients and in 95% of those assigned to adjuvant-only pembrolizumab. The most common reason for not undergoing surgery was disease progression.

Among the patients for whom safety data were available, 7% in the neoadjuvant-adjuvant group had at least one grade 3 or 4 adverse event related to pembrolizumab, whereas 7% had at least one grade 3 or 4 adverse event related to surgery.

In the adjuvant-only arm, 4% of patients had at least one grade 3 adverse event related to surgery, with no grade 4 adverse events reported.

The rates of grade 3 or 4 adverse events during adjuvant therapy were similar in the two groups, at 12% in patients assigned to neoadjuvant-adjuvant therapy and 14% in those given adjuvant-only pembrolizumab.

“Future studies can explore deescalation strategies for both surgery and adjuvant therapy, as well as approaches for patients whose melanoma does not respond to neoadjuvant therapy,” the researchers commented.

The study was funded by the National Cancer Institute and Merck Sharp and Dohme.

Dr. Patel reports numerous relationships with industry, including with Merck, manufacturer of pembrolizumab; other coauthors also have numerous relationships with industry. Dr. Weber is a regular columnist for this news organization and lists his disclosures in his Weber on Oncology column.

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

Giving pembrolizumab (Keytruda) both before and after surgery for advanced melanoma significantly improves event-free survival, show results from the phase 2 SWOG S1801 trial.

The trial involved 319 patients with operable stage IIIB to stage IV melanoma. The investigators found that patients who received pembrolizumab both before and after surgery (i.e., neoadjuvant and adjuvant therapy) fared better than those who received the drug only after surgery: The 2-year event-free survival rates were 72% vs. 49%, respectively.

The research was published in the New England Journal of Medicine, but similar results had already been presented at the European Society for Medical Oncology 2022 annual Meeting.

“It’s not just what you give; it’s when you give it,” said lead author Sapna Patel, MD, in a press release issued by the University of Texas MD Anderson Cancer Center, echoing comments she gave at ESMO 2022.

The study, she continued, “demonstrates the same treatment for resectable melanoma given before surgery can generate better outcomes.”

On the basis of their findings, Dr. Patel, who is associate professor of melanoma medical oncology at the University of Texas MD Anderson Cancer Center, Houston, said that patients with high-risk melanoma “should start immunotherapy prior to surgery to generate an immune response while the bulk of the melanoma and the anti-tumor T cells are intact.”

The mechanism of action of PD-1 blockade “relies on the presence of preexisting anti-tumor T cells attempting to attack cancer cells,” with the immunotherapy allowing the anti-tumor cells to proliferate and mediate clinical responses.

Resection of the bulk of the tumor is therefore “likely to take away some or even most of the potential anti-tumor T cells that would proliferate after PD-1 blockade,” they write.
 

Likely to apply also to nivolumab

Approached for comment, Jeffrey S. Weber, MD, PhD, professor of medicine, NYU Langone Medical Center, New York, said that outside of trials, both pembrolizumab and ipilimumab (Yervoy)/nivolumab (Opdivo) are already being used neoadjuvantly.

He thinks that the findings for neoadjuvant and adjuvant pembrolizumab could also apply to nivolumab because “the drugs are quite similar in efficacy.”

Dr. Weber told this news organization that, “even though the S1801 trial was not accepted as a registration trial by the FDA, I think that its results could very well change practice and confirm it for others who already use neoadjuvant therapy for palpable stage III melanoma.”

One question that is being addressed to an extent in the NADINA trial is whether adjuvant immunotherapy can be avoided all together and patients receive only neoadjuvant therapy, although Dr. Weber said, “I doubt that will be the case.”

Study details

In this study, patients were randomly assigned to either surgery followed by 18 doses of adjuvant pembrolizumab, or to receive 3 doses of neoadjuvant pembrolizumab followed by surgery and then 15 additional doses of adjuvant pembrolizumab.

After a median duration of follow-up of 14.7 months, there were 38 events in the neoadjuvant-adjuvant group and 67 in the adjuvant-only group.

“Events” were defined as disease progression, toxic effects, or complications that precluded surgery or the initiation of adjuvant therapy within 84 days of surgery, as well as the inability to fully resect the gross disease, melanoma recurrence, and death.

The team calculated that event-free survival was significantly longer in the neoadjuvant-adjuvant group (P = .004), with 2-year event-free survival at 72% vs. 49% in the adjuvant-only group.

“The benefit of neoadjuvant pembrolizumab was seen across all subgroups of patients,” the investigators note.

At the data cut-off, there were 14 deaths in the neoadjuvant-adjuvant group vs. 22 in the adjuvant-only group, which the researchers say is too few to allow “definitive comparison” in terms of overall survival.

Definitive surgery had been performed in 88% of neoadjuvant-adjuvant patients and in 95% of those assigned to adjuvant-only pembrolizumab. The most common reason for not undergoing surgery was disease progression.

Among the patients for whom safety data were available, 7% in the neoadjuvant-adjuvant group had at least one grade 3 or 4 adverse event related to pembrolizumab, whereas 7% had at least one grade 3 or 4 adverse event related to surgery.

In the adjuvant-only arm, 4% of patients had at least one grade 3 adverse event related to surgery, with no grade 4 adverse events reported.

The rates of grade 3 or 4 adverse events during adjuvant therapy were similar in the two groups, at 12% in patients assigned to neoadjuvant-adjuvant therapy and 14% in those given adjuvant-only pembrolizumab.

“Future studies can explore deescalation strategies for both surgery and adjuvant therapy, as well as approaches for patients whose melanoma does not respond to neoadjuvant therapy,” the researchers commented.

The study was funded by the National Cancer Institute and Merck Sharp and Dohme.

Dr. Patel reports numerous relationships with industry, including with Merck, manufacturer of pembrolizumab; other coauthors also have numerous relationships with industry. Dr. Weber is a regular columnist for this news organization and lists his disclosures in his Weber on Oncology column.

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

Giving pembrolizumab (Keytruda) both before and after surgery for advanced melanoma significantly improves event-free survival, show results from the phase 2 SWOG S1801 trial.

The trial involved 319 patients with operable stage IIIB to stage IV melanoma. The investigators found that patients who received pembrolizumab both before and after surgery (i.e., neoadjuvant and adjuvant therapy) fared better than those who received the drug only after surgery: The 2-year event-free survival rates were 72% vs. 49%, respectively.

The research was published in the New England Journal of Medicine, but similar results had already been presented at the European Society for Medical Oncology 2022 annual Meeting.

“It’s not just what you give; it’s when you give it,” said lead author Sapna Patel, MD, in a press release issued by the University of Texas MD Anderson Cancer Center, echoing comments she gave at ESMO 2022.

The study, she continued, “demonstrates the same treatment for resectable melanoma given before surgery can generate better outcomes.”

On the basis of their findings, Dr. Patel, who is associate professor of melanoma medical oncology at the University of Texas MD Anderson Cancer Center, Houston, said that patients with high-risk melanoma “should start immunotherapy prior to surgery to generate an immune response while the bulk of the melanoma and the anti-tumor T cells are intact.”

The mechanism of action of PD-1 blockade “relies on the presence of preexisting anti-tumor T cells attempting to attack cancer cells,” with the immunotherapy allowing the anti-tumor cells to proliferate and mediate clinical responses.

Resection of the bulk of the tumor is therefore “likely to take away some or even most of the potential anti-tumor T cells that would proliferate after PD-1 blockade,” they write.
 

Likely to apply also to nivolumab

Approached for comment, Jeffrey S. Weber, MD, PhD, professor of medicine, NYU Langone Medical Center, New York, said that outside of trials, both pembrolizumab and ipilimumab (Yervoy)/nivolumab (Opdivo) are already being used neoadjuvantly.

He thinks that the findings for neoadjuvant and adjuvant pembrolizumab could also apply to nivolumab because “the drugs are quite similar in efficacy.”

Dr. Weber told this news organization that, “even though the S1801 trial was not accepted as a registration trial by the FDA, I think that its results could very well change practice and confirm it for others who already use neoadjuvant therapy for palpable stage III melanoma.”

One question that is being addressed to an extent in the NADINA trial is whether adjuvant immunotherapy can be avoided all together and patients receive only neoadjuvant therapy, although Dr. Weber said, “I doubt that will be the case.”

Study details

In this study, patients were randomly assigned to either surgery followed by 18 doses of adjuvant pembrolizumab, or to receive 3 doses of neoadjuvant pembrolizumab followed by surgery and then 15 additional doses of adjuvant pembrolizumab.

After a median duration of follow-up of 14.7 months, there were 38 events in the neoadjuvant-adjuvant group and 67 in the adjuvant-only group.

“Events” were defined as disease progression, toxic effects, or complications that precluded surgery or the initiation of adjuvant therapy within 84 days of surgery, as well as the inability to fully resect the gross disease, melanoma recurrence, and death.

The team calculated that event-free survival was significantly longer in the neoadjuvant-adjuvant group (P = .004), with 2-year event-free survival at 72% vs. 49% in the adjuvant-only group.

“The benefit of neoadjuvant pembrolizumab was seen across all subgroups of patients,” the investigators note.

At the data cut-off, there were 14 deaths in the neoadjuvant-adjuvant group vs. 22 in the adjuvant-only group, which the researchers say is too few to allow “definitive comparison” in terms of overall survival.

Definitive surgery had been performed in 88% of neoadjuvant-adjuvant patients and in 95% of those assigned to adjuvant-only pembrolizumab. The most common reason for not undergoing surgery was disease progression.

Among the patients for whom safety data were available, 7% in the neoadjuvant-adjuvant group had at least one grade 3 or 4 adverse event related to pembrolizumab, whereas 7% had at least one grade 3 or 4 adverse event related to surgery.

In the adjuvant-only arm, 4% of patients had at least one grade 3 adverse event related to surgery, with no grade 4 adverse events reported.

The rates of grade 3 or 4 adverse events during adjuvant therapy were similar in the two groups, at 12% in patients assigned to neoadjuvant-adjuvant therapy and 14% in those given adjuvant-only pembrolizumab.

“Future studies can explore deescalation strategies for both surgery and adjuvant therapy, as well as approaches for patients whose melanoma does not respond to neoadjuvant therapy,” the researchers commented.

The study was funded by the National Cancer Institute and Merck Sharp and Dohme.

Dr. Patel reports numerous relationships with industry, including with Merck, manufacturer of pembrolizumab; other coauthors also have numerous relationships with industry. Dr. Weber is a regular columnist for this news organization and lists his disclosures in his Weber on Oncology column.

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

HONOLULU – With so many kids missing childhood vaccinations during the acute phase of the COVID-19 pandemic, think measles in patients who present with high fever, cough, and a maculopapular eruption.

“Measles is one of the most contagious of human viruses, and we are seeing a resurgence,” Adelaide A. Hebert, MD, professor of dermatology and pediatrics, and chief of pediatric dermatology at the Universtiy of Texas, Houston, said at the Hawaii Dermatology Seminar provided by MedscapeLIVE! “This is a re-emerging viral infection that dermatologists must recognize. Measles often starts behind the ears, and the eruption can look a lot like a drug eruption,” she noted. “Many of my pediatric colleagues have never seen a case of measles before because we have had a vaccine since 1963. Measles can almost entirely be prevented with vaccination. You get herd immunity if both doses have been administered to 95% of the population.”

In 2021, the World Health Organization estimated that 25 million children worldwide missed the measles vaccine. This caused 9 million cases of measles and 128,000 deaths in 22 countries, mainly from viral pneumonia, secondary bacterial pneumonia, and postviral encephalitis. According to the Centers for Disease Control and Prevention, 1,274 measles cases occurred in 31 states in 2019, mostly in individuals who were not vaccinated against it. Reported cases fell to 13 in 2020 but rose to 49 cases in 2021 and to 121 cases in 2022. As of Feb. 28, 2023, three cases have been reported in the United States.

“Measles spreads through direct contact with an infected person and through airborne transmission,” said Dr. Hebert, who recommended an article published in The Lancet for background on the topic. “Unlike COVID-19, measles has not mutated, so the original measles vaccine will work very well.”

Common clinical signs of measles include a generalized, maculopapular eruption lasting for 3 days or more, a temperature above 101° F plus cough, coryza, or conjunctivitis. Confirmation of measles can be made by PCR for viral RNA. Clinicians can also send a blood draw to the state public health lab for analysis. The serologic standard is a fourfold rise or fall in IgG titer with a paired sample sent 10-14 days after the initial collection.

“You can administer immune globulin up to 6 days after exposure to potentially prevent measles or decrease severity [in] immunocompromised hosts not previously vaccinated,” she said. The recommended intramuscular dose is 0.5 mL/kg, up to a dose of 15 mL/kg. Treatment is supportive and focused on relieving common symptoms and providing nutritional support. Administration of vitamin A is currently recommended for all children with acute measles.

Vitamin A supplements are available either as capsules (50,000 IU; 100,000 IU; 200,000 IU) or in liquid form. Parenteral formulations are also available. “Capsules need to be cut open and the contents squeezed into the mouths of children younger than 2 years,” Dr. Hebert said. “Capsules have the advantage that they can be given to mothers for administration at home.”

The recommended dosage of vitamin A in children is as follows, she said:

• Aged 12 months or older: 200,000 IU daily for 2 days.
• Aged 6 to 11 months: 100,000 IU daily for 2 days.
• Aged 6 months or younger: 50,000 IU daily for 2 days.

The American Academy of Pediatrics recommends a third dose given 2-4 weeks later to children with clinical signs and symptoms of vitamin A deficiency.

In an interview following the meeting, Moise L. Levy, MD, professor of internal medicine and pediatrics at the University of Texas, Austin, emphasized that when clinicians evaluate pediatric patients with viral symptoms such as fever, cough, and skin eruption, “measles should be in the differential diagnosis.” The 2022 uptick in measles cases “would be another reason to engage in regular vaccinations.”

Dr. Hebert disclosed that she is a consultant or advisor for AbbVie, Almirall, Amryt Pharma, Arcutis Biotherapeutics, Beiersdorf, Dermavant Sciences, Galderma Laboratories, L’Oreal, Novan, Ortho Dermatologics, Pfizer, and Verrica.

Dr. Levy disclosed that he is consultant or advisor for Abeona, Castle Creek, Dusa Pharma, Krystal Bio, Novan, Regeneron, and Sanofi-Genzyme.

MedscapeLIVE! and this news organization are owned by the same parent company.

HONOLULU – With so many kids missing childhood vaccinations during the acute phase of the COVID-19 pandemic, think measles in patients who present with high fever, cough, and a maculopapular eruption.

“Measles is one of the most contagious of human viruses, and we are seeing a resurgence,” Adelaide A. Hebert, MD, professor of dermatology and pediatrics, and chief of pediatric dermatology at the Universtiy of Texas, Houston, said at the Hawaii Dermatology Seminar provided by MedscapeLIVE! “This is a re-emerging viral infection that dermatologists must recognize. Measles often starts behind the ears, and the eruption can look a lot like a drug eruption,” she noted. “Many of my pediatric colleagues have never seen a case of measles before because we have had a vaccine since 1963. Measles can almost entirely be prevented with vaccination. You get herd immunity if both doses have been administered to 95% of the population.”

In 2021, the World Health Organization estimated that 25 million children worldwide missed the measles vaccine. This caused 9 million cases of measles and 128,000 deaths in 22 countries, mainly from viral pneumonia, secondary bacterial pneumonia, and postviral encephalitis. According to the Centers for Disease Control and Prevention, 1,274 measles cases occurred in 31 states in 2019, mostly in individuals who were not vaccinated against it. Reported cases fell to 13 in 2020 but rose to 49 cases in 2021 and to 121 cases in 2022. As of Feb. 28, 2023, three cases have been reported in the United States.

“Measles spreads through direct contact with an infected person and through airborne transmission,” said Dr. Hebert, who recommended an article published in The Lancet for background on the topic. “Unlike COVID-19, measles has not mutated, so the original measles vaccine will work very well.”

Common clinical signs of measles include a generalized, maculopapular eruption lasting for 3 days or more, a temperature above 101° F plus cough, coryza, or conjunctivitis. Confirmation of measles can be made by PCR for viral RNA. Clinicians can also send a blood draw to the state public health lab for analysis. The serologic standard is a fourfold rise or fall in IgG titer with a paired sample sent 10-14 days after the initial collection.

“You can administer immune globulin up to 6 days after exposure to potentially prevent measles or decrease severity [in] immunocompromised hosts not previously vaccinated,” she said. The recommended intramuscular dose is 0.5 mL/kg, up to a dose of 15 mL/kg. Treatment is supportive and focused on relieving common symptoms and providing nutritional support. Administration of vitamin A is currently recommended for all children with acute measles.

Vitamin A supplements are available either as capsules (50,000 IU; 100,000 IU; 200,000 IU) or in liquid form. Parenteral formulations are also available. “Capsules need to be cut open and the contents squeezed into the mouths of children younger than 2 years,” Dr. Hebert said. “Capsules have the advantage that they can be given to mothers for administration at home.”

The recommended dosage of vitamin A in children is as follows, she said:

• Aged 12 months or older: 200,000 IU daily for 2 days.
• Aged 6 to 11 months: 100,000 IU daily for 2 days.
• Aged 6 months or younger: 50,000 IU daily for 2 days.

The American Academy of Pediatrics recommends a third dose given 2-4 weeks later to children with clinical signs and symptoms of vitamin A deficiency.

In an interview following the meeting, Moise L. Levy, MD, professor of internal medicine and pediatrics at the University of Texas, Austin, emphasized that when clinicians evaluate pediatric patients with viral symptoms such as fever, cough, and skin eruption, “measles should be in the differential diagnosis.” The 2022 uptick in measles cases “would be another reason to engage in regular vaccinations.”

Dr. Hebert disclosed that she is a consultant or advisor for AbbVie, Almirall, Amryt Pharma, Arcutis Biotherapeutics, Beiersdorf, Dermavant Sciences, Galderma Laboratories, L’Oreal, Novan, Ortho Dermatologics, Pfizer, and Verrica.

Dr. Levy disclosed that he is consultant or advisor for Abeona, Castle Creek, Dusa Pharma, Krystal Bio, Novan, Regeneron, and Sanofi-Genzyme.

MedscapeLIVE! and this news organization are owned by the same parent company.

HONOLULU – With so many kids missing childhood vaccinations during the acute phase of the COVID-19 pandemic, think measles in patients who present with high fever, cough, and a maculopapular eruption.

“Measles is one of the most contagious of human viruses, and we are seeing a resurgence,” Adelaide A. Hebert, MD, professor of dermatology and pediatrics, and chief of pediatric dermatology at the Universtiy of Texas, Houston, said at the Hawaii Dermatology Seminar provided by MedscapeLIVE! “This is a re-emerging viral infection that dermatologists must recognize. Measles often starts behind the ears, and the eruption can look a lot like a drug eruption,” she noted. “Many of my pediatric colleagues have never seen a case of measles before because we have had a vaccine since 1963. Measles can almost entirely be prevented with vaccination. You get herd immunity if both doses have been administered to 95% of the population.”

In 2021, the World Health Organization estimated that 25 million children worldwide missed the measles vaccine. This caused 9 million cases of measles and 128,000 deaths in 22 countries, mainly from viral pneumonia, secondary bacterial pneumonia, and postviral encephalitis. According to the Centers for Disease Control and Prevention, 1,274 measles cases occurred in 31 states in 2019, mostly in individuals who were not vaccinated against it. Reported cases fell to 13 in 2020 but rose to 49 cases in 2021 and to 121 cases in 2022. As of Feb. 28, 2023, three cases have been reported in the United States.

“Measles spreads through direct contact with an infected person and through airborne transmission,” said Dr. Hebert, who recommended an article published in The Lancet for background on the topic. “Unlike COVID-19, measles has not mutated, so the original measles vaccine will work very well.”

Common clinical signs of measles include a generalized, maculopapular eruption lasting for 3 days or more, a temperature above 101° F plus cough, coryza, or conjunctivitis. Confirmation of measles can be made by PCR for viral RNA. Clinicians can also send a blood draw to the state public health lab for analysis. The serologic standard is a fourfold rise or fall in IgG titer with a paired sample sent 10-14 days after the initial collection.

“You can administer immune globulin up to 6 days after exposure to potentially prevent measles or decrease severity [in] immunocompromised hosts not previously vaccinated,” she said. The recommended intramuscular dose is 0.5 mL/kg, up to a dose of 15 mL/kg. Treatment is supportive and focused on relieving common symptoms and providing nutritional support. Administration of vitamin A is currently recommended for all children with acute measles.

Vitamin A supplements are available either as capsules (50,000 IU; 100,000 IU; 200,000 IU) or in liquid form. Parenteral formulations are also available. “Capsules need to be cut open and the contents squeezed into the mouths of children younger than 2 years,” Dr. Hebert said. “Capsules have the advantage that they can be given to mothers for administration at home.”

The recommended dosage of vitamin A in children is as follows, she said:

• Aged 12 months or older: 200,000 IU daily for 2 days.
• Aged 6 to 11 months: 100,000 IU daily for 2 days.
• Aged 6 months or younger: 50,000 IU daily for 2 days.

The American Academy of Pediatrics recommends a third dose given 2-4 weeks later to children with clinical signs and symptoms of vitamin A deficiency.

In an interview following the meeting, Moise L. Levy, MD, professor of internal medicine and pediatrics at the University of Texas, Austin, emphasized that when clinicians evaluate pediatric patients with viral symptoms such as fever, cough, and skin eruption, “measles should be in the differential diagnosis.” The 2022 uptick in measles cases “would be another reason to engage in regular vaccinations.”

Dr. Hebert disclosed that she is a consultant or advisor for AbbVie, Almirall, Amryt Pharma, Arcutis Biotherapeutics, Beiersdorf, Dermavant Sciences, Galderma Laboratories, L’Oreal, Novan, Ortho Dermatologics, Pfizer, and Verrica.

Dr. Levy disclosed that he is consultant or advisor for Abeona, Castle Creek, Dusa Pharma, Krystal Bio, Novan, Regeneron, and Sanofi-Genzyme.

MedscapeLIVE! and this news organization are owned by the same parent company.

For adults with eosinophilic esophagitis (EoE), eliminating animal milk alone appears to be as effective for treating the disease as forgoing milk and five other foods, according to a new report.

A one-food elimination diet (1FED) led to histologic remission in 34% of patients, as determined on the basis of eosinophil count at 6 weeks, and in 40% of patients who followed a six-food elimination diet (6FED) – a nonstatistical difference, the research team wrote.

“The takeaway message is that one-food (milk) elimination is an effective treatment and a reasonable first-line treatment for EoE,” senior study author Marc Rothenberg, MD, PhD, a professor of pediatrics and director of the allergy and immunology division at the Cincinnati Center for Eosinophilic Disorders at Cincinnati Children’s Hospital Medical Center, said in an interview.

“The study was designed by the Consortium of Eosinophilic Disease Researchers (CEGIR), which includes the nation’s top institutions working with patient advocacy groups, together with the National Institutes of Health,” he said. “The group, under advice from patients, determined that it was an important question to research if one-food elimination would be effective – and how effective – compared with six-food elimination.”

The study was published in The Lancet Gastroenterology and Hepatology.
 

Studying EOE and food elimination

Previous studies have found that eliminating six common foods that trigger esophageal injury – milk, eggs, wheat, soy, fish, and nuts – can substantially reduce EoE symptoms. The 6FED has become a common approach to managing the disease.

In recent years, however, researchers have conducted small, nonrandomized studies of the less restrictive 1FED and have found some success.

In a multisite, randomized trial, Dr. Rothenberg and colleagues compared the 6FED with the 1FED among 129 adults aged 18-60 years with a confirmed EoE diagnosis, active EoE symptoms, and a high number of eosinophils in esophageal tissue. The participants enrolled at 1 of 10 U.S. medical centers that participate in CEGIR, which is part of the NIH-funded Rare Diseases Clinical Research Network.

Between 2016 and 2019, 67 participants were assigned to the 1FED group, which eliminated only animal milk from the diet, and 62 participants were assigned to the 6FED group, which eliminated milk, eggs, wheat, soy, fish/shellfish, and peanuts/tree nuts. After following the diet for 6 weeks, participants underwent an upper endoscopy exam and esophageal tissue biopsy. The primary endpoint was the proportion of patients with histologic remission, or a peak count of less than 15 eosinophils per high-power field (eos/hpf).

If the number of eosinophils indicated that EoE was in remission, the participant exited the study. If EoE wasn’t in remission, those who were on 1FED could proceed to 6FED, and those who were on 6FED could take fluticasone propionate 880 mcg two times per day with an unrestricted diet. Both groups followed the protocols for 6 weeks and underwent another exam with tissue biopsy.

At 6 weeks, 25 patients (40%) on 6FED and 23 patients (34%) on 1FED achieved histologic remission. The difference was not statistically significant.

There were also no significant differences between the groups at stricter thresholds for partial remission, defined as peak counts of 10 eos/hpf or less and 6 eos/hpf or less. The rate of complete remission (at a peak count of ≤ 1 eos/hpf) favored 6FED, at 19% versus 6% among 1FED.

The two diets had a similar impact across several other measures, including reduction in peak eosinophil counts, reduction in EoE symptoms, and improvement in quality of life. For 6FED versus 1FED, the mean changes from baseline in the Eosinophilic Esophagitis Histology Scoring System were –0.23 versus –0.15. In addition, the mean changes in the Eosinophilic Esophagitis Endoscopic Reference Score were 1 versus –0.6, and in the Eosinophilic Esophagitis Activity Index, they were –8.2 versus –3. None of the differences were significant.

Among the patients who didn’t respond to 1FED, 21 opted to follow 6FED in the study’s second phase. Of those patients, nine (43%) attained remission after following the more restrictive diet. Among the 11 patients who didn’t initially respond to 6FED and who opted to receive fluticasone propionate, nine patients (82%) achieved remission.

“We examined a series of validated endpoints that have not previously been examined in diet trials,” Dr. Rothenberg said. “We are surprised to see that one food was equally effective as six foods.”
 

Incorporating food elimination therapy

Dr. Rothenberg and colleagues are continuing their research into EoE and food-elimination diets, with a strong focus on furthering diet therapy. In particular, the research team wants to understand how to potentially add milk – and other foods – back to the diet.

Wael Sayej, MD, associate professor of pediatrics at the University of Massachusetts Baystate Regional Campus, Springfield, has found success with the one-food elimination diet among children with EoE, he said in an interview.

In a retrospective study, Dr. Sayej and colleagues found that a one-food elimination diet was an effective first-line treatment option for pediatric patients.

“Once we get past the one-food or two-food elimination, it becomes much more difficult and cumbersome for patients to follow,” said Dr. Sayej, who is also a pediatric gastroenterologist with Baystate Health in Springfield and who wasn’t involved with the CEGIR study. “Obviously, I prefer my patients to follow a strict dairy-free diet as long-term therapy, rather than have them on a medication for the rest of their life.”

Dr. Sayej advises patients to follow the one-food elimination diet in his practice. If patients aren’t responsive, he offers options for additional dietary elimination or initiation of steroid therapy.

“The most important thing about initiating dietary elimination therapy is to take the time to educate the patient and family about the disease, the risks or complications associated with untreated disease, and the pros and cons of the treatment options,” he said.

The study was cofunded by the National Institute of Allergy and Infectious Diseases, the National Center for Advancing Translational Sciences, and the National Institute of Diabetes and Digestive and Kidney Diseases. The authors have research, consultant, and leadership relationships with several pharmaceutical companies and organizations not related to this study. Dr. Sayej disclosed no relevant financial relationships.
 

For adults with eosinophilic esophagitis (EoE), eliminating animal milk alone appears to be as effective for treating the disease as forgoing milk and five other foods, according to a new report.

A one-food elimination diet (1FED) led to histologic remission in 34% of patients, as determined on the basis of eosinophil count at 6 weeks, and in 40% of patients who followed a six-food elimination diet (6FED) – a nonstatistical difference, the research team wrote.

“The takeaway message is that one-food (milk) elimination is an effective treatment and a reasonable first-line treatment for EoE,” senior study author Marc Rothenberg, MD, PhD, a professor of pediatrics and director of the allergy and immunology division at the Cincinnati Center for Eosinophilic Disorders at Cincinnati Children’s Hospital Medical Center, said in an interview.

“The study was designed by the Consortium of Eosinophilic Disease Researchers (CEGIR), which includes the nation’s top institutions working with patient advocacy groups, together with the National Institutes of Health,” he said. “The group, under advice from patients, determined that it was an important question to research if one-food elimination would be effective – and how effective – compared with six-food elimination.”

The study was published in The Lancet Gastroenterology and Hepatology.
 

Studying EOE and food elimination

Previous studies have found that eliminating six common foods that trigger esophageal injury – milk, eggs, wheat, soy, fish, and nuts – can substantially reduce EoE symptoms. The 6FED has become a common approach to managing the disease.

In recent years, however, researchers have conducted small, nonrandomized studies of the less restrictive 1FED and have found some success.

In a multisite, randomized trial, Dr. Rothenberg and colleagues compared the 6FED with the 1FED among 129 adults aged 18-60 years with a confirmed EoE diagnosis, active EoE symptoms, and a high number of eosinophils in esophageal tissue. The participants enrolled at 1 of 10 U.S. medical centers that participate in CEGIR, which is part of the NIH-funded Rare Diseases Clinical Research Network.

Between 2016 and 2019, 67 participants were assigned to the 1FED group, which eliminated only animal milk from the diet, and 62 participants were assigned to the 6FED group, which eliminated milk, eggs, wheat, soy, fish/shellfish, and peanuts/tree nuts. After following the diet for 6 weeks, participants underwent an upper endoscopy exam and esophageal tissue biopsy. The primary endpoint was the proportion of patients with histologic remission, or a peak count of less than 15 eosinophils per high-power field (eos/hpf).

If the number of eosinophils indicated that EoE was in remission, the participant exited the study. If EoE wasn’t in remission, those who were on 1FED could proceed to 6FED, and those who were on 6FED could take fluticasone propionate 880 mcg two times per day with an unrestricted diet. Both groups followed the protocols for 6 weeks and underwent another exam with tissue biopsy.

At 6 weeks, 25 patients (40%) on 6FED and 23 patients (34%) on 1FED achieved histologic remission. The difference was not statistically significant.

There were also no significant differences between the groups at stricter thresholds for partial remission, defined as peak counts of 10 eos/hpf or less and 6 eos/hpf or less. The rate of complete remission (at a peak count of ≤ 1 eos/hpf) favored 6FED, at 19% versus 6% among 1FED.

The two diets had a similar impact across several other measures, including reduction in peak eosinophil counts, reduction in EoE symptoms, and improvement in quality of life. For 6FED versus 1FED, the mean changes from baseline in the Eosinophilic Esophagitis Histology Scoring System were –0.23 versus –0.15. In addition, the mean changes in the Eosinophilic Esophagitis Endoscopic Reference Score were 1 versus –0.6, and in the Eosinophilic Esophagitis Activity Index, they were –8.2 versus –3. None of the differences were significant.

Among the patients who didn’t respond to 1FED, 21 opted to follow 6FED in the study’s second phase. Of those patients, nine (43%) attained remission after following the more restrictive diet. Among the 11 patients who didn’t initially respond to 6FED and who opted to receive fluticasone propionate, nine patients (82%) achieved remission.

“We examined a series of validated endpoints that have not previously been examined in diet trials,” Dr. Rothenberg said. “We are surprised to see that one food was equally effective as six foods.”
 

Incorporating food elimination therapy

Dr. Rothenberg and colleagues are continuing their research into EoE and food-elimination diets, with a strong focus on furthering diet therapy. In particular, the research team wants to understand how to potentially add milk – and other foods – back to the diet.

Wael Sayej, MD, associate professor of pediatrics at the University of Massachusetts Baystate Regional Campus, Springfield, has found success with the one-food elimination diet among children with EoE, he said in an interview.

In a retrospective study, Dr. Sayej and colleagues found that a one-food elimination diet was an effective first-line treatment option for pediatric patients.

“Once we get past the one-food or two-food elimination, it becomes much more difficult and cumbersome for patients to follow,” said Dr. Sayej, who is also a pediatric gastroenterologist with Baystate Health in Springfield and who wasn’t involved with the CEGIR study. “Obviously, I prefer my patients to follow a strict dairy-free diet as long-term therapy, rather than have them on a medication for the rest of their life.”

Dr. Sayej advises patients to follow the one-food elimination diet in his practice. If patients aren’t responsive, he offers options for additional dietary elimination or initiation of steroid therapy.

“The most important thing about initiating dietary elimination therapy is to take the time to educate the patient and family about the disease, the risks or complications associated with untreated disease, and the pros and cons of the treatment options,” he said.

The study was cofunded by the National Institute of Allergy and Infectious Diseases, the National Center for Advancing Translational Sciences, and the National Institute of Diabetes and Digestive and Kidney Diseases. The authors have research, consultant, and leadership relationships with several pharmaceutical companies and organizations not related to this study. Dr. Sayej disclosed no relevant financial relationships.
 

For adults with eosinophilic esophagitis (EoE), eliminating animal milk alone appears to be as effective for treating the disease as forgoing milk and five other foods, according to a new report.

A one-food elimination diet (1FED) led to histologic remission in 34% of patients, as determined on the basis of eosinophil count at 6 weeks, and in 40% of patients who followed a six-food elimination diet (6FED) – a nonstatistical difference, the research team wrote.

“The takeaway message is that one-food (milk) elimination is an effective treatment and a reasonable first-line treatment for EoE,” senior study author Marc Rothenberg, MD, PhD, a professor of pediatrics and director of the allergy and immunology division at the Cincinnati Center for Eosinophilic Disorders at Cincinnati Children’s Hospital Medical Center, said in an interview.

“The study was designed by the Consortium of Eosinophilic Disease Researchers (CEGIR), which includes the nation’s top institutions working with patient advocacy groups, together with the National Institutes of Health,” he said. “The group, under advice from patients, determined that it was an important question to research if one-food elimination would be effective – and how effective – compared with six-food elimination.”

The study was published in The Lancet Gastroenterology and Hepatology.
 

Studying EOE and food elimination

Previous studies have found that eliminating six common foods that trigger esophageal injury – milk, eggs, wheat, soy, fish, and nuts – can substantially reduce EoE symptoms. The 6FED has become a common approach to managing the disease.

In recent years, however, researchers have conducted small, nonrandomized studies of the less restrictive 1FED and have found some success.

In a multisite, randomized trial, Dr. Rothenberg and colleagues compared the 6FED with the 1FED among 129 adults aged 18-60 years with a confirmed EoE diagnosis, active EoE symptoms, and a high number of eosinophils in esophageal tissue. The participants enrolled at 1 of 10 U.S. medical centers that participate in CEGIR, which is part of the NIH-funded Rare Diseases Clinical Research Network.

Between 2016 and 2019, 67 participants were assigned to the 1FED group, which eliminated only animal milk from the diet, and 62 participants were assigned to the 6FED group, which eliminated milk, eggs, wheat, soy, fish/shellfish, and peanuts/tree nuts. After following the diet for 6 weeks, participants underwent an upper endoscopy exam and esophageal tissue biopsy. The primary endpoint was the proportion of patients with histologic remission, or a peak count of less than 15 eosinophils per high-power field (eos/hpf).

If the number of eosinophils indicated that EoE was in remission, the participant exited the study. If EoE wasn’t in remission, those who were on 1FED could proceed to 6FED, and those who were on 6FED could take fluticasone propionate 880 mcg two times per day with an unrestricted diet. Both groups followed the protocols for 6 weeks and underwent another exam with tissue biopsy.

At 6 weeks, 25 patients (40%) on 6FED and 23 patients (34%) on 1FED achieved histologic remission. The difference was not statistically significant.

There were also no significant differences between the groups at stricter thresholds for partial remission, defined as peak counts of 10 eos/hpf or less and 6 eos/hpf or less. The rate of complete remission (at a peak count of ≤ 1 eos/hpf) favored 6FED, at 19% versus 6% among 1FED.

The two diets had a similar impact across several other measures, including reduction in peak eosinophil counts, reduction in EoE symptoms, and improvement in quality of life. For 6FED versus 1FED, the mean changes from baseline in the Eosinophilic Esophagitis Histology Scoring System were –0.23 versus –0.15. In addition, the mean changes in the Eosinophilic Esophagitis Endoscopic Reference Score were 1 versus –0.6, and in the Eosinophilic Esophagitis Activity Index, they were –8.2 versus –3. None of the differences were significant.

Among the patients who didn’t respond to 1FED, 21 opted to follow 6FED in the study’s second phase. Of those patients, nine (43%) attained remission after following the more restrictive diet. Among the 11 patients who didn’t initially respond to 6FED and who opted to receive fluticasone propionate, nine patients (82%) achieved remission.

“We examined a series of validated endpoints that have not previously been examined in diet trials,” Dr. Rothenberg said. “We are surprised to see that one food was equally effective as six foods.”
 

Incorporating food elimination therapy

Dr. Rothenberg and colleagues are continuing their research into EoE and food-elimination diets, with a strong focus on furthering diet therapy. In particular, the research team wants to understand how to potentially add milk – and other foods – back to the diet.

Wael Sayej, MD, associate professor of pediatrics at the University of Massachusetts Baystate Regional Campus, Springfield, has found success with the one-food elimination diet among children with EoE, he said in an interview.

In a retrospective study, Dr. Sayej and colleagues found that a one-food elimination diet was an effective first-line treatment option for pediatric patients.

“Once we get past the one-food or two-food elimination, it becomes much more difficult and cumbersome for patients to follow,” said Dr. Sayej, who is also a pediatric gastroenterologist with Baystate Health in Springfield and who wasn’t involved with the CEGIR study. “Obviously, I prefer my patients to follow a strict dairy-free diet as long-term therapy, rather than have them on a medication for the rest of their life.”

Dr. Sayej advises patients to follow the one-food elimination diet in his practice. If patients aren’t responsive, he offers options for additional dietary elimination or initiation of steroid therapy.

“The most important thing about initiating dietary elimination therapy is to take the time to educate the patient and family about the disease, the risks or complications associated with untreated disease, and the pros and cons of the treatment options,” he said.

The study was cofunded by the National Institute of Allergy and Infectious Diseases, the National Center for Advancing Translational Sciences, and the National Institute of Diabetes and Digestive and Kidney Diseases. The authors have research, consultant, and leadership relationships with several pharmaceutical companies and organizations not related to this study. Dr. Sayej disclosed no relevant financial relationships.
 

In February, the US House of Representatives hurriedly passed the Stopping Home Office Work’s Unproductive Problems (SHOW UP) Act, H.R. 139, a bill that calls into question the contributions of federal employees allowed to work from home and resets telework policies to those in place in 2019. Its author, House Oversight Committee Chairman James Comer (R, Kentucky) claimed that this change was necessary because the expansion of federal telework during the COVID-19 pandemic “has crippled the ability of agencies to get their jobs done and created backlogs.” His targets included the US Department of Veterans Affairs (VA), where, he charged, “veterans have been unable…to obtain care they have earned.” He added, “it’s hard to argue that teleworking has helped the VA.” 

While oversight of government programs is an authority of Congress, the SHOW UP Act is based on unsubstantiated assumptions of dereliction. It also disregards the devastating impact the proposed changes will have on veterans’ ability to receive care and inaccurately implies improving it. As the Senate considers the bill, they should take heed of these and other facts involving this often misunderstood form of labor.

COVID-19 irrevocably transformed the use of virtual care within the VA and across the world. Even as the pandemic subsides, public and private health care systems have continued to use telework-centered telehealth far above prepandemic levels, especially for mental health and primary care. Employers, including the VA, capitalize on telework for its benefits to both consumers and the workforce. For consumers, research supports the clinical effectiveness of telemental health service, as well as its cost-effectiveness and consumer satisfaction. On the workforce side, research has documented heightened productivity, lower distractibility, and higher job satisfaction among counselors who shifted to remote work.

Remote work also serves as a key tool in attracting and retaining a qualified workforce. As one VA service chief explained, “I am having enough trouble competing with the private sector, where extensive telework is now the norm. If telework options were rolled back, the private sector will have a field day picking off my best staff.” These comments are consistent with the data. McKinsey’s American Opportunity Survey shows that Americans have embraced remote work and want more of it. Recent data from Gallup show that 6 of 10 currently exclusively remote employees would be extremely likely to change companies if they lost their remote flexibility. Further, Gallup data show that when an employee’s location preference does not match their current work location, burnout rises, and engagement drops.   

Between 2019 and 2023, the VA’s telework expansion is what has enabled it to meet the growing demand for mental health services. VA is keeping pace by having 2 or more clinicians rotate between home and a shared VA office. Forcing these hybrid practitioners to work full time at VA facilities would drastically reduce the number of patients they can care for. There simply are not enough offices on crammed VA grounds to house staff who telework today. The net result would be that fewer appointments would be available, creating longer wait times. And that is just for existing patients. It does not factor in the expected influx due to new veteran eligibility made possible by the toxic exposures PACT Act.

Here is another good example of crucial VA telework: With the advent of the 988 Suicide & Crisis Lifeline, VA is adding more than 1000 new Veterans Crisis Line responders. All these new positions are remote. The SHOW UP Act would inhibit this expansion of lifesaving programs.

Veterans want more, not fewer, telehealth options. At a House Committee on Veterans’ Affairs hearing this past September, the VA reported that most veterans would prefer to receive mental health services virtually than to have to commute to a VA medical center or clinic. Telehealth benefits veterans in meaningful ways, including that it reduces their travel time, travel expense, depletion of sick leave, and need for childcare. Veterans with posttraumatic stress disorder, military sexual trauma, those with mobility issues, or those who struggle with the stigma of mental health treatment may prefer the familiarity of their own homes for care. Virtual options also relieve a patient’s need to enter a hospital and be unnecessarily exposed to contagious viruses. That’s safer not only for veterans but also for VA staff.

Finally, virtual care improves treatment. Research has revealed that the likelihood of missing telehealth appointments is lower than for in-person appointments. When patients miss appointments, continuity of care is disrupted, and health care outcomes are diminished. 

The pandemic is receding, but the advantages of telework-centered virtual care are greater than ever. Political representatives who want to show up for veterans should do everything in their power to expand—not cut—VA’s ability to authorize working from home.

In February, the US House of Representatives hurriedly passed the Stopping Home Office Work’s Unproductive Problems (SHOW UP) Act, H.R. 139, a bill that calls into question the contributions of federal employees allowed to work from home and resets telework policies to those in place in 2019. Its author, House Oversight Committee Chairman James Comer (R, Kentucky) claimed that this change was necessary because the expansion of federal telework during the COVID-19 pandemic “has crippled the ability of agencies to get their jobs done and created backlogs.” His targets included the US Department of Veterans Affairs (VA), where, he charged, “veterans have been unable…to obtain care they have earned.” He added, “it’s hard to argue that teleworking has helped the VA.” 

While oversight of government programs is an authority of Congress, the SHOW UP Act is based on unsubstantiated assumptions of dereliction. It also disregards the devastating impact the proposed changes will have on veterans’ ability to receive care and inaccurately implies improving it. As the Senate considers the bill, they should take heed of these and other facts involving this often misunderstood form of labor.

COVID-19 irrevocably transformed the use of virtual care within the VA and across the world. Even as the pandemic subsides, public and private health care systems have continued to use telework-centered telehealth far above prepandemic levels, especially for mental health and primary care. Employers, including the VA, capitalize on telework for its benefits to both consumers and the workforce. For consumers, research supports the clinical effectiveness of telemental health service, as well as its cost-effectiveness and consumer satisfaction. On the workforce side, research has documented heightened productivity, lower distractibility, and higher job satisfaction among counselors who shifted to remote work.

Remote work also serves as a key tool in attracting and retaining a qualified workforce. As one VA service chief explained, “I am having enough trouble competing with the private sector, where extensive telework is now the norm. If telework options were rolled back, the private sector will have a field day picking off my best staff.” These comments are consistent with the data. McKinsey’s American Opportunity Survey shows that Americans have embraced remote work and want more of it. Recent data from Gallup show that 6 of 10 currently exclusively remote employees would be extremely likely to change companies if they lost their remote flexibility. Further, Gallup data show that when an employee’s location preference does not match their current work location, burnout rises, and engagement drops.   

Between 2019 and 2023, the VA’s telework expansion is what has enabled it to meet the growing demand for mental health services. VA is keeping pace by having 2 or more clinicians rotate between home and a shared VA office. Forcing these hybrid practitioners to work full time at VA facilities would drastically reduce the number of patients they can care for. There simply are not enough offices on crammed VA grounds to house staff who telework today. The net result would be that fewer appointments would be available, creating longer wait times. And that is just for existing patients. It does not factor in the expected influx due to new veteran eligibility made possible by the toxic exposures PACT Act.

Here is another good example of crucial VA telework: With the advent of the 988 Suicide & Crisis Lifeline, VA is adding more than 1000 new Veterans Crisis Line responders. All these new positions are remote. The SHOW UP Act would inhibit this expansion of lifesaving programs.

Veterans want more, not fewer, telehealth options. At a House Committee on Veterans’ Affairs hearing this past September, the VA reported that most veterans would prefer to receive mental health services virtually than to have to commute to a VA medical center or clinic. Telehealth benefits veterans in meaningful ways, including that it reduces their travel time, travel expense, depletion of sick leave, and need for childcare. Veterans with posttraumatic stress disorder, military sexual trauma, those with mobility issues, or those who struggle with the stigma of mental health treatment may prefer the familiarity of their own homes for care. Virtual options also relieve a patient’s need to enter a hospital and be unnecessarily exposed to contagious viruses. That’s safer not only for veterans but also for VA staff.

Finally, virtual care improves treatment. Research has revealed that the likelihood of missing telehealth appointments is lower than for in-person appointments. When patients miss appointments, continuity of care is disrupted, and health care outcomes are diminished. 

The pandemic is receding, but the advantages of telework-centered virtual care are greater than ever. Political representatives who want to show up for veterans should do everything in their power to expand—not cut—VA’s ability to authorize working from home.

In February, the US House of Representatives hurriedly passed the Stopping Home Office Work’s Unproductive Problems (SHOW UP) Act, H.R. 139, a bill that calls into question the contributions of federal employees allowed to work from home and resets telework policies to those in place in 2019. Its author, House Oversight Committee Chairman James Comer (R, Kentucky) claimed that this change was necessary because the expansion of federal telework during the COVID-19 pandemic “has crippled the ability of agencies to get their jobs done and created backlogs.” His targets included the US Department of Veterans Affairs (VA), where, he charged, “veterans have been unable…to obtain care they have earned.” He added, “it’s hard to argue that teleworking has helped the VA.” 

While oversight of government programs is an authority of Congress, the SHOW UP Act is based on unsubstantiated assumptions of dereliction. It also disregards the devastating impact the proposed changes will have on veterans’ ability to receive care and inaccurately implies improving it. As the Senate considers the bill, they should take heed of these and other facts involving this often misunderstood form of labor.

COVID-19 irrevocably transformed the use of virtual care within the VA and across the world. Even as the pandemic subsides, public and private health care systems have continued to use telework-centered telehealth far above prepandemic levels, especially for mental health and primary care. Employers, including the VA, capitalize on telework for its benefits to both consumers and the workforce. For consumers, research supports the clinical effectiveness of telemental health service, as well as its cost-effectiveness and consumer satisfaction. On the workforce side, research has documented heightened productivity, lower distractibility, and higher job satisfaction among counselors who shifted to remote work.

Remote work also serves as a key tool in attracting and retaining a qualified workforce. As one VA service chief explained, “I am having enough trouble competing with the private sector, where extensive telework is now the norm. If telework options were rolled back, the private sector will have a field day picking off my best staff.” These comments are consistent with the data. McKinsey’s American Opportunity Survey shows that Americans have embraced remote work and want more of it. Recent data from Gallup show that 6 of 10 currently exclusively remote employees would be extremely likely to change companies if they lost their remote flexibility. Further, Gallup data show that when an employee’s location preference does not match their current work location, burnout rises, and engagement drops.   

Between 2019 and 2023, the VA’s telework expansion is what has enabled it to meet the growing demand for mental health services. VA is keeping pace by having 2 or more clinicians rotate between home and a shared VA office. Forcing these hybrid practitioners to work full time at VA facilities would drastically reduce the number of patients they can care for. There simply are not enough offices on crammed VA grounds to house staff who telework today. The net result would be that fewer appointments would be available, creating longer wait times. And that is just for existing patients. It does not factor in the expected influx due to new veteran eligibility made possible by the toxic exposures PACT Act.

Here is another good example of crucial VA telework: With the advent of the 988 Suicide & Crisis Lifeline, VA is adding more than 1000 new Veterans Crisis Line responders. All these new positions are remote. The SHOW UP Act would inhibit this expansion of lifesaving programs.

Veterans want more, not fewer, telehealth options. At a House Committee on Veterans’ Affairs hearing this past September, the VA reported that most veterans would prefer to receive mental health services virtually than to have to commute to a VA medical center or clinic. Telehealth benefits veterans in meaningful ways, including that it reduces their travel time, travel expense, depletion of sick leave, and need for childcare. Veterans with posttraumatic stress disorder, military sexual trauma, those with mobility issues, or those who struggle with the stigma of mental health treatment may prefer the familiarity of their own homes for care. Virtual options also relieve a patient’s need to enter a hospital and be unnecessarily exposed to contagious viruses. That’s safer not only for veterans but also for VA staff.

Finally, virtual care improves treatment. Research has revealed that the likelihood of missing telehealth appointments is lower than for in-person appointments. When patients miss appointments, continuity of care is disrupted, and health care outcomes are diminished. 

The pandemic is receding, but the advantages of telework-centered virtual care are greater than ever. Political representatives who want to show up for veterans should do everything in their power to expand—not cut—VA’s ability to authorize working from home.

NEW ORLEANS – Twenty cardiology clinics successfully intensified the medical care they gave patients with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD) after receiving a simple and scalable investigational intervention that gave the clinics’ staffs guidance on best prescribing practices and implementation and also provided quality-improvement feedback.

Within a year, these clinics quadrupled optimal medical management of these patients, compared with control clinics, in a randomized trial involving a total of 43 clinics and 1,049 patients.

“This multifaceted intervention is effective in increasing the prescription of evidence-based therapies in adults with T2D and ASCVD,” Neha J. Pagidipati, MD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Mitchel L. Zoler/MDedge News

“The next step is to scale this intervention across cardiology practices” interested in improving the quality of care they deliver to these patients, added Dr. Pagidipati, a cardiologist specializing in cardiometabolic disease prevention at Duke University in Durham, N.C.

The goal is getting patients on triple therapy

The primary outcome of the COORDINATE-Diabetes trial was the change in the number of patients with T2D and ASCVD who received prescriptions for agents from three recommended medication classes and at recommended dosages: a high-intensity statin, a renin-angiotensin system inhibitor (RASi), and at least one agent from either of two classes that have both cardiovascular-protective and antihyperglycemic effects: the sodium-glucose cotransporter 2 (SGLT2) inhibitors, or the glucagonlike peptide 1 (GLP-1)–receptor agonists.

Among the 457 patients treated at the 20 cardiology clinics who received the quality-improvement intervention, 37.9% were on the promoted triple therapy after 12 months, compared with 14.5% of the 588 patients treated at the 23 clinics that continued with their usual care approach. This 23.4–percentage point increase in triple-class prescribing at recommended dosages represented a significant 4.4-fold increase in the goal prescribing endpoint after adjustment for possible confounders, Dr. Pagidipati reported.

Simultaneously with her report, the findings also appeared online in JAMA.

At baseline, 41%-50% of the patients were on both a high-intensity statin and a RASi, with a total of about 58%-67% on a high-intensity statin and about 70%-75% on a RASi. Fewer than 1% of patients were on SGLT2 inhibitors or GLP-1–receptor agonists at baseline. By design, no patient could be on all three categories of medication at baseline.

At their last follow-up visit (after 12 months for 97% of patients, or after 6 months for the remainder) 71% of the patients at practices that received the intervention were on a high-intensity statin, 81% were taking a RASi, and 60% were on an SGLT2 inhibitor or GLP-1–receptor agonist. Among the control patients, 58% were on a high-intensity statin, 68% on a RASi, and 36% were on one of the antihyperglycemic agents.

Effective interventions and the need for a champion

The clinics randomized to the active arm received instruction from a three-member team, either from an in-person or virtual one-time visit, on an intervention comprising several initiatives:

• Analysis of the barriers to evidence-based care at each clinic.
• Development of local interdisciplinary care pathways to address the identified barriers.
• Facilitation of care coordination among clinicians – particularly among cardiology, endocrinology, and primary care clinicians.
• Education of the clinic staff, including provision of educational materials.
• Auditing of clinic performance using specified metrics and feedback on the findings.

Clinics in the usual care group were given current clinical practice guidelines.

The investigational intervention was, by design, “low-tech and designed to be scalable,” explained Dr. Pagidipati, and once the COVID pandemic started the intervention team shifted to a virtual consultation with participating practices that was mostly front-loaded, followed by monthly phone calls to give clinics feedback on their progress.

Among the most helpful aspects of the intervention was involving the entire clinic staff, including pharmacists, nurses, and advanced care practitioners; boosting familiarity with the relevant medications and their appropriate use; and advice on navigating insurance-coverage barriers such as prior authorizations.

“What was most critical was having a local champion who took on making this effort an important part” of what the clinic was trying to do, she explained. “All it takes is passion, and the tenacity of a bulldog,” Dr. Pagidipati said.

Research advances often don’t translate into management changes

“We don’t do a great job of translating findings from trials to patient care, so any method we can use to improve that will improve practice,” commented Kristen B. Campbell, PharmD, a clinical pharmacist at Duke who was not involved in the study.

“Although the trial was not powered to look at patient outcomes, we think that patients will benefit” because all the recommended medication uses have been proven to help patients in prior trials, Dr. Campbell noted.

Mitchel L. Zoler/MDedge News

“A particular strength of this study was its simple design. All the interventions are low-tech and scalable.”

The low level of use of guideline-directed medical therapy in American adults with type 2 diabetes and atherosclerotic cardiovascular disease is “incredible,” said Christopher B. Granger, MD, a senior investigator on the study and a cardiologist and professor at Duke.

The researchers who ran the study are now focused on evaluating which cardiology clinics and patients had the most success from the intervention and are using that information to further refine implementation. They are also planning to encourage cardiology practices as well as other relevant medical groups to incorporate the intervention and implementation model used in the trial. The intervention program is detailed and available at no charge on the COORDINATE-Diabetes website.

COORDINATE-Diabetes received funding from Boehringer Ingelheim and Eli Lilly. Dr. Pagidipati has received personal fees from Boehringer Ingelheim, Lilly, AstraZeneca, Novartis, Novo Nordisk, Merck, and CRISPR Therapeutics, and she has received research grants from Amgen, Novartis, Novo Nordisk, and Eggland’s Best. Dr. Campbell had no disclosures. Dr. Granger has received personal fees and research funding from numerous companies.

NEW ORLEANS – Twenty cardiology clinics successfully intensified the medical care they gave patients with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD) after receiving a simple and scalable investigational intervention that gave the clinics’ staffs guidance on best prescribing practices and implementation and also provided quality-improvement feedback.

Within a year, these clinics quadrupled optimal medical management of these patients, compared with control clinics, in a randomized trial involving a total of 43 clinics and 1,049 patients.

“This multifaceted intervention is effective in increasing the prescription of evidence-based therapies in adults with T2D and ASCVD,” Neha J. Pagidipati, MD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Mitchel L. Zoler/MDedge News

“The next step is to scale this intervention across cardiology practices” interested in improving the quality of care they deliver to these patients, added Dr. Pagidipati, a cardiologist specializing in cardiometabolic disease prevention at Duke University in Durham, N.C.

The goal is getting patients on triple therapy

The primary outcome of the COORDINATE-Diabetes trial was the change in the number of patients with T2D and ASCVD who received prescriptions for agents from three recommended medication classes and at recommended dosages: a high-intensity statin, a renin-angiotensin system inhibitor (RASi), and at least one agent from either of two classes that have both cardiovascular-protective and antihyperglycemic effects: the sodium-glucose cotransporter 2 (SGLT2) inhibitors, or the glucagonlike peptide 1 (GLP-1)–receptor agonists.

Among the 457 patients treated at the 20 cardiology clinics who received the quality-improvement intervention, 37.9% were on the promoted triple therapy after 12 months, compared with 14.5% of the 588 patients treated at the 23 clinics that continued with their usual care approach. This 23.4–percentage point increase in triple-class prescribing at recommended dosages represented a significant 4.4-fold increase in the goal prescribing endpoint after adjustment for possible confounders, Dr. Pagidipati reported.

Simultaneously with her report, the findings also appeared online in JAMA.

At baseline, 41%-50% of the patients were on both a high-intensity statin and a RASi, with a total of about 58%-67% on a high-intensity statin and about 70%-75% on a RASi. Fewer than 1% of patients were on SGLT2 inhibitors or GLP-1–receptor agonists at baseline. By design, no patient could be on all three categories of medication at baseline.

At their last follow-up visit (after 12 months for 97% of patients, or after 6 months for the remainder) 71% of the patients at practices that received the intervention were on a high-intensity statin, 81% were taking a RASi, and 60% were on an SGLT2 inhibitor or GLP-1–receptor agonist. Among the control patients, 58% were on a high-intensity statin, 68% on a RASi, and 36% were on one of the antihyperglycemic agents.

Effective interventions and the need for a champion

The clinics randomized to the active arm received instruction from a three-member team, either from an in-person or virtual one-time visit, on an intervention comprising several initiatives:

• Analysis of the barriers to evidence-based care at each clinic.
• Development of local interdisciplinary care pathways to address the identified barriers.
• Facilitation of care coordination among clinicians – particularly among cardiology, endocrinology, and primary care clinicians.
• Education of the clinic staff, including provision of educational materials.
• Auditing of clinic performance using specified metrics and feedback on the findings.

Clinics in the usual care group were given current clinical practice guidelines.

The investigational intervention was, by design, “low-tech and designed to be scalable,” explained Dr. Pagidipati, and once the COVID pandemic started the intervention team shifted to a virtual consultation with participating practices that was mostly front-loaded, followed by monthly phone calls to give clinics feedback on their progress.

Among the most helpful aspects of the intervention was involving the entire clinic staff, including pharmacists, nurses, and advanced care practitioners; boosting familiarity with the relevant medications and their appropriate use; and advice on navigating insurance-coverage barriers such as prior authorizations.

“What was most critical was having a local champion who took on making this effort an important part” of what the clinic was trying to do, she explained. “All it takes is passion, and the tenacity of a bulldog,” Dr. Pagidipati said.

Research advances often don’t translate into management changes

“We don’t do a great job of translating findings from trials to patient care, so any method we can use to improve that will improve practice,” commented Kristen B. Campbell, PharmD, a clinical pharmacist at Duke who was not involved in the study.

“Although the trial was not powered to look at patient outcomes, we think that patients will benefit” because all the recommended medication uses have been proven to help patients in prior trials, Dr. Campbell noted.

Mitchel L. Zoler/MDedge News

“A particular strength of this study was its simple design. All the interventions are low-tech and scalable.”

The low level of use of guideline-directed medical therapy in American adults with type 2 diabetes and atherosclerotic cardiovascular disease is “incredible,” said Christopher B. Granger, MD, a senior investigator on the study and a cardiologist and professor at Duke.

The researchers who ran the study are now focused on evaluating which cardiology clinics and patients had the most success from the intervention and are using that information to further refine implementation. They are also planning to encourage cardiology practices as well as other relevant medical groups to incorporate the intervention and implementation model used in the trial. The intervention program is detailed and available at no charge on the COORDINATE-Diabetes website.

COORDINATE-Diabetes received funding from Boehringer Ingelheim and Eli Lilly. Dr. Pagidipati has received personal fees from Boehringer Ingelheim, Lilly, AstraZeneca, Novartis, Novo Nordisk, Merck, and CRISPR Therapeutics, and she has received research grants from Amgen, Novartis, Novo Nordisk, and Eggland’s Best. Dr. Campbell had no disclosures. Dr. Granger has received personal fees and research funding from numerous companies.

NEW ORLEANS – Twenty cardiology clinics successfully intensified the medical care they gave patients with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD) after receiving a simple and scalable investigational intervention that gave the clinics’ staffs guidance on best prescribing practices and implementation and also provided quality-improvement feedback.

Within a year, these clinics quadrupled optimal medical management of these patients, compared with control clinics, in a randomized trial involving a total of 43 clinics and 1,049 patients.

“This multifaceted intervention is effective in increasing the prescription of evidence-based therapies in adults with T2D and ASCVD,” Neha J. Pagidipati, MD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Mitchel L. Zoler/MDedge News

“The next step is to scale this intervention across cardiology practices” interested in improving the quality of care they deliver to these patients, added Dr. Pagidipati, a cardiologist specializing in cardiometabolic disease prevention at Duke University in Durham, N.C.

The goal is getting patients on triple therapy

The primary outcome of the COORDINATE-Diabetes trial was the change in the number of patients with T2D and ASCVD who received prescriptions for agents from three recommended medication classes and at recommended dosages: a high-intensity statin, a renin-angiotensin system inhibitor (RASi), and at least one agent from either of two classes that have both cardiovascular-protective and antihyperglycemic effects: the sodium-glucose cotransporter 2 (SGLT2) inhibitors, or the glucagonlike peptide 1 (GLP-1)–receptor agonists.

Among the 457 patients treated at the 20 cardiology clinics who received the quality-improvement intervention, 37.9% were on the promoted triple therapy after 12 months, compared with 14.5% of the 588 patients treated at the 23 clinics that continued with their usual care approach. This 23.4–percentage point increase in triple-class prescribing at recommended dosages represented a significant 4.4-fold increase in the goal prescribing endpoint after adjustment for possible confounders, Dr. Pagidipati reported.

Simultaneously with her report, the findings also appeared online in JAMA.

At baseline, 41%-50% of the patients were on both a high-intensity statin and a RASi, with a total of about 58%-67% on a high-intensity statin and about 70%-75% on a RASi. Fewer than 1% of patients were on SGLT2 inhibitors or GLP-1–receptor agonists at baseline. By design, no patient could be on all three categories of medication at baseline.

At their last follow-up visit (after 12 months for 97% of patients, or after 6 months for the remainder) 71% of the patients at practices that received the intervention were on a high-intensity statin, 81% were taking a RASi, and 60% were on an SGLT2 inhibitor or GLP-1–receptor agonist. Among the control patients, 58% were on a high-intensity statin, 68% on a RASi, and 36% were on one of the antihyperglycemic agents.

Effective interventions and the need for a champion

The clinics randomized to the active arm received instruction from a three-member team, either from an in-person or virtual one-time visit, on an intervention comprising several initiatives:

• Analysis of the barriers to evidence-based care at each clinic.
• Development of local interdisciplinary care pathways to address the identified barriers.
• Facilitation of care coordination among clinicians – particularly among cardiology, endocrinology, and primary care clinicians.
• Education of the clinic staff, including provision of educational materials.
• Auditing of clinic performance using specified metrics and feedback on the findings.

Clinics in the usual care group were given current clinical practice guidelines.

The investigational intervention was, by design, “low-tech and designed to be scalable,” explained Dr. Pagidipati, and once the COVID pandemic started the intervention team shifted to a virtual consultation with participating practices that was mostly front-loaded, followed by monthly phone calls to give clinics feedback on their progress.

Among the most helpful aspects of the intervention was involving the entire clinic staff, including pharmacists, nurses, and advanced care practitioners; boosting familiarity with the relevant medications and their appropriate use; and advice on navigating insurance-coverage barriers such as prior authorizations.

“What was most critical was having a local champion who took on making this effort an important part” of what the clinic was trying to do, she explained. “All it takes is passion, and the tenacity of a bulldog,” Dr. Pagidipati said.

Research advances often don’t translate into management changes

“We don’t do a great job of translating findings from trials to patient care, so any method we can use to improve that will improve practice,” commented Kristen B. Campbell, PharmD, a clinical pharmacist at Duke who was not involved in the study.

“Although the trial was not powered to look at patient outcomes, we think that patients will benefit” because all the recommended medication uses have been proven to help patients in prior trials, Dr. Campbell noted.

Mitchel L. Zoler/MDedge News

“A particular strength of this study was its simple design. All the interventions are low-tech and scalable.”

The low level of use of guideline-directed medical therapy in American adults with type 2 diabetes and atherosclerotic cardiovascular disease is “incredible,” said Christopher B. Granger, MD, a senior investigator on the study and a cardiologist and professor at Duke.

The researchers who ran the study are now focused on evaluating which cardiology clinics and patients had the most success from the intervention and are using that information to further refine implementation. They are also planning to encourage cardiology practices as well as other relevant medical groups to incorporate the intervention and implementation model used in the trial. The intervention program is detailed and available at no charge on the COORDINATE-Diabetes website.

COORDINATE-Diabetes received funding from Boehringer Ingelheim and Eli Lilly. Dr. Pagidipati has received personal fees from Boehringer Ingelheim, Lilly, AstraZeneca, Novartis, Novo Nordisk, Merck, and CRISPR Therapeutics, and she has received research grants from Amgen, Novartis, Novo Nordisk, and Eggland’s Best. Dr. Campbell had no disclosures. Dr. Granger has received personal fees and research funding from numerous companies.

More clinical guidance is needed for monitoring interstitial lung disease (ILD) in patients with rheumatoid arthritis, according to a new commentary.

Though ILD is a leading cause of death among patients with RA, these patients are not routinely screened for ILD, the authors say, and there are currently no guidelines on how to monitor ILD progression in patients with RA.

A.Prof Frank Gaillard, Radiopaedia.org

“ILD associated with rheumatoid arthritis is a disease for which there’s been very little research done, so it’s an area of rheumatology where there are many unknowns,” lead author Elizabeth R. Volkmann, MD, who codirects the connective tissue disease–related interstitial lung disease (CTD-ILD) program at University of California, Los Angeles, told this news organization.

The commentary was published in The Lancet Rheumatology.
 

Defining disease

One of the major unknowns is how to define the disease, she said. RA patients sometimes undergo imaging for other medical reasons, and interstitial lung abnormalities are incidentally detected. These patients can be classified as having “preclinical” or “subclinical” ILD, as they do not yet have symptoms; however, there is no consensus as to what these terms mean, the commentary authors write. “The other problem that we have with these terms is that it sometimes creates the perception that this is a nonworrisome feature of rheumatoid arthritis,” Dr. Volkmann said, although the condition should be followed closely.

“We know we can detect imaging features of ILD in people who may not yet have symptoms, and we need to know when to define a clinically important informality that requires follow-up or treatment,” added John M. Davis III, MD, a rheumatologist at the Mayo Clinic, Rochester, Minn. He was not involved with the work.

Mayo Clinic

Dr. Volkmann proposed eliminating the prefixes “pre” and “sub” when referring to ILD. “In other connective tissue diseases, like systemic sclerosis, for example, we can use the term ‘limited’ or ‘extensive’ ILD, based on the extent of involvement of the ILD on high-resolution computed tomography (HRCT) imaging,” she said. “This could potentially be something that is applied to how we classify patients with RA-ILD.”
 

Tracking ILD progression

Once ILD is identified, monitoring its progression poses challenges, as respiratory symptoms may be difficult to detect. RA patients may already be avoiding exercise because of joint pain, so they may not notice shortness of breath during physical activity, noted Jessica K. Gordon, MD, of the Hospital for Special Surgery, New York, in an interview with this news organization. She was not involved with the commentary. Cough is a potential symptom of ILD, but cough can also be the result of allergies, postnasal drip, or reflux, she said. Making the distinction between “preclinical” and symptomatic disease can be “complicated,” she added; “you may have to really dig.”

Hospital for Special Surgery

Additionally, there has been little research on the outcomes of patients with preclinical or subclinical ILD and clinical ILD, the commentary authors write. “It is therefore conceivable that some patients with rheumatoid arthritis diagnosed with preclinical or subclinical ILD could potentially have worse outcomes if both the rheumatoid arthritis and ILD are not monitored closely,” they note.

To better track RA-associated ILD for patients with and those without symptoms, the authors advocate for monitoring patients using pulmonary testing and CT scanning, as well as evaluating symptoms. How often these assessments should be conducted depends on the individual, they note. In her own practice, Dr. Volkmann sees patients every 3 months to evaluate their symptoms and conduct pulmonary function tests (PFTs). For patients early in the course of ILD, she orders HRCT imaging once per year.

For Dr. Davis, the frequency of follow-up depends on the severity of ILD. “For minimally symptomatic patients without compromised lung function, we would generally follow annually. For patients with symptomatic ILD on stable therapy, we may monitor every 6 months. For patients with active/progressive ILD, we would generally be following at least every 1-3 months,” he said.

Screening and future research

While there is no evidence to recommend screening patients for ILD using CT, there are certain risk factors for ILD in RA patients, including a history of smoking, male sex, and high RA disease activity despite antirheumatic treatment, Dr. Volkmann said. In both of their practices, Dr. Davis and Dr. Volkmann screen with RA via HRCT and PFTs for ILD for patients with known risk factors that predispose them to the lung condition and/or for patients who report respiratory symptoms.

National Jewish Health

“We still don’t have an algorithm [for screening patients], and that is a desperate need in this field,” added Joshua J. Solomon, MD, a pulmonologist at National Jewish Health, Denver, whose research focuses on RA-associated ILD. While recommendations state that all patients with scleroderma should be screened with CT, ILD incidence is lower among patients with RA, and thus these screening recommendations need to be narrowed, he said. But more research is needed to better fine tune recommendations, he said; “The only thing you can do is give some expert consensus until there are good data.”

Dr. Volkmann has received consulting and speaking fees from Boehringer Ingelheim and institutional support for performing studies on systemic sclerosis for Kadmon, Forbius, Boehringer Ingelheim, Horizon, and Prometheus. Dr. Gordon, Dr. Davis, and Dr. Solomon report no relevant financial relationships.

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

More clinical guidance is needed for monitoring interstitial lung disease (ILD) in patients with rheumatoid arthritis, according to a new commentary.

Though ILD is a leading cause of death among patients with RA, these patients are not routinely screened for ILD, the authors say, and there are currently no guidelines on how to monitor ILD progression in patients with RA.

A.Prof Frank Gaillard, Radiopaedia.org

“ILD associated with rheumatoid arthritis is a disease for which there’s been very little research done, so it’s an area of rheumatology where there are many unknowns,” lead author Elizabeth R. Volkmann, MD, who codirects the connective tissue disease–related interstitial lung disease (CTD-ILD) program at University of California, Los Angeles, told this news organization.

The commentary was published in The Lancet Rheumatology.
 

Defining disease

One of the major unknowns is how to define the disease, she said. RA patients sometimes undergo imaging for other medical reasons, and interstitial lung abnormalities are incidentally detected. These patients can be classified as having “preclinical” or “subclinical” ILD, as they do not yet have symptoms; however, there is no consensus as to what these terms mean, the commentary authors write. “The other problem that we have with these terms is that it sometimes creates the perception that this is a nonworrisome feature of rheumatoid arthritis,” Dr. Volkmann said, although the condition should be followed closely.

“We know we can detect imaging features of ILD in people who may not yet have symptoms, and we need to know when to define a clinically important informality that requires follow-up or treatment,” added John M. Davis III, MD, a rheumatologist at the Mayo Clinic, Rochester, Minn. He was not involved with the work.

Mayo Clinic

Dr. Volkmann proposed eliminating the prefixes “pre” and “sub” when referring to ILD. “In other connective tissue diseases, like systemic sclerosis, for example, we can use the term ‘limited’ or ‘extensive’ ILD, based on the extent of involvement of the ILD on high-resolution computed tomography (HRCT) imaging,” she said. “This could potentially be something that is applied to how we classify patients with RA-ILD.”
 

Tracking ILD progression

Once ILD is identified, monitoring its progression poses challenges, as respiratory symptoms may be difficult to detect. RA patients may already be avoiding exercise because of joint pain, so they may not notice shortness of breath during physical activity, noted Jessica K. Gordon, MD, of the Hospital for Special Surgery, New York, in an interview with this news organization. She was not involved with the commentary. Cough is a potential symptom of ILD, but cough can also be the result of allergies, postnasal drip, or reflux, she said. Making the distinction between “preclinical” and symptomatic disease can be “complicated,” she added; “you may have to really dig.”

Hospital for Special Surgery

Additionally, there has been little research on the outcomes of patients with preclinical or subclinical ILD and clinical ILD, the commentary authors write. “It is therefore conceivable that some patients with rheumatoid arthritis diagnosed with preclinical or subclinical ILD could potentially have worse outcomes if both the rheumatoid arthritis and ILD are not monitored closely,” they note.

To better track RA-associated ILD for patients with and those without symptoms, the authors advocate for monitoring patients using pulmonary testing and CT scanning, as well as evaluating symptoms. How often these assessments should be conducted depends on the individual, they note. In her own practice, Dr. Volkmann sees patients every 3 months to evaluate their symptoms and conduct pulmonary function tests (PFTs). For patients early in the course of ILD, she orders HRCT imaging once per year.

For Dr. Davis, the frequency of follow-up depends on the severity of ILD. “For minimally symptomatic patients without compromised lung function, we would generally follow annually. For patients with symptomatic ILD on stable therapy, we may monitor every 6 months. For patients with active/progressive ILD, we would generally be following at least every 1-3 months,” he said.

Screening and future research

While there is no evidence to recommend screening patients for ILD using CT, there are certain risk factors for ILD in RA patients, including a history of smoking, male sex, and high RA disease activity despite antirheumatic treatment, Dr. Volkmann said. In both of their practices, Dr. Davis and Dr. Volkmann screen with RA via HRCT and PFTs for ILD for patients with known risk factors that predispose them to the lung condition and/or for patients who report respiratory symptoms.

National Jewish Health

“We still don’t have an algorithm [for screening patients], and that is a desperate need in this field,” added Joshua J. Solomon, MD, a pulmonologist at National Jewish Health, Denver, whose research focuses on RA-associated ILD. While recommendations state that all patients with scleroderma should be screened with CT, ILD incidence is lower among patients with RA, and thus these screening recommendations need to be narrowed, he said. But more research is needed to better fine tune recommendations, he said; “The only thing you can do is give some expert consensus until there are good data.”

Dr. Volkmann has received consulting and speaking fees from Boehringer Ingelheim and institutional support for performing studies on systemic sclerosis for Kadmon, Forbius, Boehringer Ingelheim, Horizon, and Prometheus. Dr. Gordon, Dr. Davis, and Dr. Solomon report no relevant financial relationships.

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

More clinical guidance is needed for monitoring interstitial lung disease (ILD) in patients with rheumatoid arthritis, according to a new commentary.

Though ILD is a leading cause of death among patients with RA, these patients are not routinely screened for ILD, the authors say, and there are currently no guidelines on how to monitor ILD progression in patients with RA.

A.Prof Frank Gaillard, Radiopaedia.org

“ILD associated with rheumatoid arthritis is a disease for which there’s been very little research done, so it’s an area of rheumatology where there are many unknowns,” lead author Elizabeth R. Volkmann, MD, who codirects the connective tissue disease–related interstitial lung disease (CTD-ILD) program at University of California, Los Angeles, told this news organization.

The commentary was published in The Lancet Rheumatology.
 

Defining disease

One of the major unknowns is how to define the disease, she said. RA patients sometimes undergo imaging for other medical reasons, and interstitial lung abnormalities are incidentally detected. These patients can be classified as having “preclinical” or “subclinical” ILD, as they do not yet have symptoms; however, there is no consensus as to what these terms mean, the commentary authors write. “The other problem that we have with these terms is that it sometimes creates the perception that this is a nonworrisome feature of rheumatoid arthritis,” Dr. Volkmann said, although the condition should be followed closely.

“We know we can detect imaging features of ILD in people who may not yet have symptoms, and we need to know when to define a clinically important informality that requires follow-up or treatment,” added John M. Davis III, MD, a rheumatologist at the Mayo Clinic, Rochester, Minn. He was not involved with the work.

Mayo Clinic

Dr. Volkmann proposed eliminating the prefixes “pre” and “sub” when referring to ILD. “In other connective tissue diseases, like systemic sclerosis, for example, we can use the term ‘limited’ or ‘extensive’ ILD, based on the extent of involvement of the ILD on high-resolution computed tomography (HRCT) imaging,” she said. “This could potentially be something that is applied to how we classify patients with RA-ILD.”
 

Tracking ILD progression

Once ILD is identified, monitoring its progression poses challenges, as respiratory symptoms may be difficult to detect. RA patients may already be avoiding exercise because of joint pain, so they may not notice shortness of breath during physical activity, noted Jessica K. Gordon, MD, of the Hospital for Special Surgery, New York, in an interview with this news organization. She was not involved with the commentary. Cough is a potential symptom of ILD, but cough can also be the result of allergies, postnasal drip, or reflux, she said. Making the distinction between “preclinical” and symptomatic disease can be “complicated,” she added; “you may have to really dig.”

Hospital for Special Surgery

Additionally, there has been little research on the outcomes of patients with preclinical or subclinical ILD and clinical ILD, the commentary authors write. “It is therefore conceivable that some patients with rheumatoid arthritis diagnosed with preclinical or subclinical ILD could potentially have worse outcomes if both the rheumatoid arthritis and ILD are not monitored closely,” they note.

To better track RA-associated ILD for patients with and those without symptoms, the authors advocate for monitoring patients using pulmonary testing and CT scanning, as well as evaluating symptoms. How often these assessments should be conducted depends on the individual, they note. In her own practice, Dr. Volkmann sees patients every 3 months to evaluate their symptoms and conduct pulmonary function tests (PFTs). For patients early in the course of ILD, she orders HRCT imaging once per year.

For Dr. Davis, the frequency of follow-up depends on the severity of ILD. “For minimally symptomatic patients without compromised lung function, we would generally follow annually. For patients with symptomatic ILD on stable therapy, we may monitor every 6 months. For patients with active/progressive ILD, we would generally be following at least every 1-3 months,” he said.

Screening and future research

While there is no evidence to recommend screening patients for ILD using CT, there are certain risk factors for ILD in RA patients, including a history of smoking, male sex, and high RA disease activity despite antirheumatic treatment, Dr. Volkmann said. In both of their practices, Dr. Davis and Dr. Volkmann screen with RA via HRCT and PFTs for ILD for patients with known risk factors that predispose them to the lung condition and/or for patients who report respiratory symptoms.

National Jewish Health

“We still don’t have an algorithm [for screening patients], and that is a desperate need in this field,” added Joshua J. Solomon, MD, a pulmonologist at National Jewish Health, Denver, whose research focuses on RA-associated ILD. While recommendations state that all patients with scleroderma should be screened with CT, ILD incidence is lower among patients with RA, and thus these screening recommendations need to be narrowed, he said. But more research is needed to better fine tune recommendations, he said; “The only thing you can do is give some expert consensus until there are good data.”

Dr. Volkmann has received consulting and speaking fees from Boehringer Ingelheim and institutional support for performing studies on systemic sclerosis for Kadmon, Forbius, Boehringer Ingelheim, Horizon, and Prometheus. Dr. Gordon, Dr. Davis, and Dr. Solomon report no relevant financial relationships.

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

A new real-world analysis finds that severe infection rates were higher than in clinical trials in 67 patients with chronic lymphocytic leukemia (CLL) or B-cell lymphoma who took ibrutinib (Imbruvica), idelalisib (Zydelig), or venetoclax (Venclexta).

For example, “the rate of severe infection for ibrutinib in clinical trials ranged from 12.8% to 45% with median follow-up ranging from 27 to 65 months. In our study, the rate of severe infection was 45.3% within a shorter median follow-up period of 23.3 months,” said study lead author Amanda Tey, MPharm, a hematology pharmacist with Monash Health in Clayton, Australia, in an interview.

The results suggest that “real-world severe infection risk is higher than previously appreciated,” said Ms. Tey, whose findings were published in the European Journal of Hematology. “Poor performance status and a high comorbidity burden further increase this risk.”

According to the study, there are limited data about real-world infection rates for patients with CLL or B-cell lymphoma who take the three drugs.

Both the underlying blood cancer and the drugs themselves may disrupt the immune system in these patients, Ms. Tey noted. “Ibrutinib inhibits interleukin-2-inducible T-cell kinase, which has a role in T-cell maturation. Idelalisib reduces regulatory T-cell activity and natural killer cell and neutrophil inflammatory responses. Venetoclax is associated with a high rate of neutropenia.”

For the new retrospective, single-center study, researchers tracked adult patients who’d received the drugs from 2014 to 2021 in a hospital network serving 1.5 million people in the Australian state of Victoria. The primary outcome was severe infection of grade 3 or higher. Patients were excluded for such factors as having been primarily treated at other facilities, receiving less than 30 days of treatment, or having been treated for other indications such as primary central nervous system lymphoma.

Of the 67 patients in the study, the numbers taking the drugs were 53 (ibrutinib), 8 (idelalisib), and 6 (venetoclax). Eleven patients took more than one drug. Median age was 73 years, and 73% of patients were male.

Patients spent a median 23.3, 4.8, and 3.5 months taking ibrutinib, idelalisib, and venetoclax, respectively, before treatment stopped or data were collected. Patients were commonly prescribed antimicrobials to prevent pneumocystis jirovecii pneumonia and herpes simplex virus (HSV)/varicella zoster virus (VZV) infection.

Researchers found that 48% of the patients had at least one serious infection: 45% of those on ibrutinib, 63% of those on idelalisib, and 50% of those on venetoclax. Seven patients died of infections.

In comparison, the researchers reported, a systematic review of idelalisib in blood cancer clinical trials reported an overall infection rate of 28%, while clinical trials reported an infection rate of 17.5%-22% in patients taking venetoclax for CLL.

Poor performance status and higher levels of comorbidity were linked to higher risk of infection, and infections occurred at a median of 5.4 months.

Lead author Ms. Tey highlighted the fact that most of the patients in the new study had relapsed/refractory disease. The infection risk in the real-world first-line setting is unknown, she said. “Furthermore, due to the size of our study and high uptake of antimicrobial prophylaxis, the optimal prophylaxis strategy for these patients remains unclear.”

In an interview, infectious disease physician Gemma Reynolds, MChD, MPH, of Austin Health and Peter MacCallum Cancer Center in Melbourne, said the study findings reflect “a lot of what we know from other observational studies and clinical practice. There is a risk of infection, and serious infection, associated with these agents. Sometimes the pathogen is classically opportunistic, but often it is bacterial, and respiratory sites are common. Infections often occur early into a course of therapy.”

Dr. Reynolds, who didn’t take part in the study, urged colleagues to cast a wide net if a patient appears to have an infection but doesn’t respond to conventional therapies such as antibiotics. “Unusual infections are possible,” she said, and aggressive early workups may be advisable via blood cultures, viral swabs, sputum culture, early imaging, bronchoscopy, and preemptive monitoring in patients with a prior infection history with a disease such as CMV.

Alessandra Ferrajoli, MD, a hematologist/oncologist at MD Anderson Cancer Center who also didn’t take part in the study, agreed in an interview that the findings reflect those found in other reports. “It should be highlighted that the population studied is at particular high risk for infections given the high proportion of patients with recurrent disease (85%), many patients with concurrent hypogammaglobulinemia (64%), and the patient median age of 73 years and a high comorbidities burden,” she said. “In my view, this explains the higher rate of infections reported in this study, when compared to other case series.”

Dr. Ferrajoli added that there’s no standard antimicrobial prophylaxis for patients with B-cell malignancies receiving targeted therapies. “Anti-HSV/VZV prophylaxis is commonly implemented. Additional antiviral, antimicrobial, and antifungal prophylaxis should be used based on patients’ absolute neutrophil and T-cell count and individual risk factors, including prior history of infections such as CMV, prior splenectomy, and history of invasive fungal infections.”

The study was funded by Monash Health, the National Health and Medical Research Council (Australia), and the Society of Hospital Pharmacists of Australia. Ms. Tey reported no disclosures. Some of the study authors reported multiple disclosures. Dr. Reynolds discloses a PhD scholarship from the National Health and Medical Research Council. Dr. Ferrajoli reported no disclosures.