User login
When treating AD in children, experts consider adherence, other aspects of treatment
ASHEVILLE, N.C. – according to a three-member expert panel mulling over strategies at the annual meeting of the Society for Pediatric Dermatology.
In introductory remarks, the three panelists briefly addressed different aspects for controlling AD, including drugs in the pipeline, the potential value of alternative therapies, and whom to blame when compliance is poor.
But panel discussion following these presentations provided an opportunity for audience engagement on practical strategies for improving AD control.
In her formal remarks prior to the panel discussion, Amy S. Paller, MD, professor of dermatology and pediatrics and chair of dermatology, Northwestern University, Chicago, and a pediatric dermatologist at the Lurie Children’s Hospital of Chicago, described emerging AD treatments. This included an update on the status of the interleukin-13 (IL-13) inhibitors tralokinumab (Adbry), which was approved by the FDA for treating AD in adults in December 2021, and lebrikizumab, which is thought likely to be soon approved in the United States on the basis of two recently published phase 3 trials.
Along with dupilumab (Dupixent) for moderate-to-severe AD in children who do not respond to optimized use of topical therapies, these new biologics appear likely to further expand choices for AD control for adults (and for kids with AD too, if eventually licensed in children), according to the data from the phase 3 studies.
During a panel discussion that followed, Stephen Gellis, MD, pediatric dermatologist and former chief of pediatric dermatology at Boston Children’s Hospital and Harvard Medical School, raised the point of optimizing tried and true topical therapies before using systemic agents. He noted that parents sometimes pressure clinicians to use a biologic – and that moving too quickly to the latest and most expensive drugs may not be necessary.
Dr. Paller acknowledged that she, like many pediatric dermatologists, employed immunosuppressants as her drugs of choice for many years – commonly starting with a few months of cyclosporine before transitioning to methotrexate, which has a delayed onset of action. In fact, she still uses this regimen in some children.
However, she now prefers dupilumab, which is the first biologic available for children in the United States with an AD indication in children as young as 6 months. She said dupilumab has fewer potential risks than cyclosporine, and it offers clinically meaningful improvement in most children. She noted that current guidelines discourage the use of systemic corticosteroids for AD in children, given their potential toxicity.
She strongly agreed with Dr. Gellis that clinicians should resist pressure to use any systemic agent if children are responding well to topical medications. In her own practice, Dr. Paller moves to systemic medications only after ensuring that there has been adherence to appropriate therapy and that there is not another diagnosis that might explain the recalcitrance to topical agents.
When a systemic medication is considered the next step, Dr. Paller reminded the audience of the importance of presenting the benefits and risks of all the options for AD control, which could include dupilumab and immunosuppressants as initial systemic therapy.
“Many parents choose biologic treatment first, given its lack of requirement for blood monitoring and faster action than methotrexate,” Dr. Paller noted.
Nevertheless, “biologics are much more costly than immunosuppressants, require an injection – which is stressful for the child and the parents – and may not be accessible for our patients,” Dr. Paller said. Cyclosporine and methotrexate are effective and are often the best options for moderate to severe disease in areas of the world where dupilumab is not available, but Dr. Paller most commonly uses these therapies only when reimbursement for dupilumab cannot be secured, injection is not an option, or when dupilumab is not sufficiently effective and tolerated.
Providing different perspectives, the two other panelists discussing the treatment of pediatric AD also saw a role for ensuring that topical agents are not offering adequate AD control before turning to the latest and most sophisticated therapies for AD.
For meeting parent expectations when children are improving slowly on topical therapies, Peter A. Lio, MD, director of the Chicago Integrative Eczema Center and clinical assistant professor of dermatology and pediatrics at Northwestern University, suggested that integrative medicine might be helpful.
For parents not fully comfortable with standard pharmacologic agents, Dr. Lio said there is evidence to support some of the complementary approaches, and these can be reassuring to parents with an interest in alternative medicines.
In Western medicine, it is common to hear terms like “attack,” “kill,” and “suppress,” disease, but alternative therapies are generally coupled with terms like “restore,” “strengthen,” and “tonify,” he said. “Who doesn’t want to be tonified?” he asked, noting that there are many sources of data suggesting that the number of patients seeking alternative medicine is “huge.” The alternative medicines are not generally taught in medical school and remain widely ignored in typical practice, but “our patients are interested even if we are not.”
Yet, there are data to support benefit from some of these alternative therapies, providing a win-win situation for patients who derive satisfaction from nontraditional therapies alone or combined with established pharmaceutical treatments.
Of these, Dr. Lio said there is support for the use of hempseed oil as a moisturizing agent and a strategy for improving barrier function in the skin of patients with AD. In a controlled crossover study, 2 teaspoons per day of dietary hempseed oil, a product that can be purchased in some grocery stores, was associated with significant reductions in skin dryness, itchiness, and use of topical medications relative to the same amount of olive oil, he noted.
Other examples include a compress made with black tea that was associated with an anti-inflammatory effect when followed by a moisturizer, a published study asserts. Although this was a trial in adults with facial dermatitis, Dr. Lio suggested that the same anti-inflammatory effect would be anticipated for other skin conditions, including AD in children.
As a third example, Dr. Lio said topical indigo, a traditional Chinese medicine used for a variety of dermatologic conditions, including psoriasis, has also demonstrated efficacy in a randomized trial, compared with vehicle for mild to severe AD.
Complementary medicines are not for everyone, but they may have a role when managing the expectations of parents who are not fully satisfied or express concern about regimens limited to mainstream therapies alone, according to Dr. Lio. In diseases that are not curable, such as AD, he thinks this is a strategy with potential for benefit and is reassuring to patients.
Another way to avoid moving to riskier or more expensive drugs quickly is to assure patients use the drugs that were prescribed first, according to Steven R. Feldman, MD, PhD, professor of dermatology, Wake Forest University, Winston-Salem, N.C.
Dr. Feldman believes that failure to adhere to therapy is basically the fault of the medical care system, not the patient. He made an analogy to a successful piano teacher, who provides a child with sheet music and then sees the child once a week to track progress. He juxtaposed this piano teacher to one who gives the child sheet music and tells the child to come back in 10 weeks for the recital. It is not hard to guess which approach would be more effective.
“Typically, doctors are worse than that second teacher,” he said. “Doctors are like a piano teacher that does not give you the sheet music but says, ‘Here is a prescription for some sheet music. Take this prescription to the sheet music store. I have no idea how much it will cost or whether your insurance will pay for it. But once you fill this prescription for sheet music, I want you to practice this every day,’ ” he said, adding, “Practicing this sheet music may cause rashes, diarrhea, or serious infection. When the patient next comes in 10-12 weeks later and is not better, the doctor says, ‘I will give you a harder piece of sheet music and maybe two or three other instruments to practice at the same time,’ ” said Dr. Feldman, expressing why the way clinicians practice might explain much of the poor adherence problem.
This largely explains why patients with AD do not immediately respond to the therapies doctors prescribe, Dr. Feldman implied, reiterating the theme that emerged from the AD panel: Better and more options are needed for AD of the most severe types, but better management, not better drugs, is typically what is needed for most patients.
Dr. Feldman, Dr. Lio, and Dr. Paller have financial relationships with more than 30 pharmaceutical and cosmetic companies, some of which manufacture therapies for atopic dermatitis.
This article was updated July 28, 2023, to clarify the comments and viewpoints of Dr. Amy Paller.
A version of this article first appeared on Medscape.com.
ASHEVILLE, N.C. – according to a three-member expert panel mulling over strategies at the annual meeting of the Society for Pediatric Dermatology.
In introductory remarks, the three panelists briefly addressed different aspects for controlling AD, including drugs in the pipeline, the potential value of alternative therapies, and whom to blame when compliance is poor.
But panel discussion following these presentations provided an opportunity for audience engagement on practical strategies for improving AD control.
In her formal remarks prior to the panel discussion, Amy S. Paller, MD, professor of dermatology and pediatrics and chair of dermatology, Northwestern University, Chicago, and a pediatric dermatologist at the Lurie Children’s Hospital of Chicago, described emerging AD treatments. This included an update on the status of the interleukin-13 (IL-13) inhibitors tralokinumab (Adbry), which was approved by the FDA for treating AD in adults in December 2021, and lebrikizumab, which is thought likely to be soon approved in the United States on the basis of two recently published phase 3 trials.
Along with dupilumab (Dupixent) for moderate-to-severe AD in children who do not respond to optimized use of topical therapies, these new biologics appear likely to further expand choices for AD control for adults (and for kids with AD too, if eventually licensed in children), according to the data from the phase 3 studies.
During a panel discussion that followed, Stephen Gellis, MD, pediatric dermatologist and former chief of pediatric dermatology at Boston Children’s Hospital and Harvard Medical School, raised the point of optimizing tried and true topical therapies before using systemic agents. He noted that parents sometimes pressure clinicians to use a biologic – and that moving too quickly to the latest and most expensive drugs may not be necessary.
Dr. Paller acknowledged that she, like many pediatric dermatologists, employed immunosuppressants as her drugs of choice for many years – commonly starting with a few months of cyclosporine before transitioning to methotrexate, which has a delayed onset of action. In fact, she still uses this regimen in some children.
However, she now prefers dupilumab, which is the first biologic available for children in the United States with an AD indication in children as young as 6 months. She said dupilumab has fewer potential risks than cyclosporine, and it offers clinically meaningful improvement in most children. She noted that current guidelines discourage the use of systemic corticosteroids for AD in children, given their potential toxicity.
She strongly agreed with Dr. Gellis that clinicians should resist pressure to use any systemic agent if children are responding well to topical medications. In her own practice, Dr. Paller moves to systemic medications only after ensuring that there has been adherence to appropriate therapy and that there is not another diagnosis that might explain the recalcitrance to topical agents.
When a systemic medication is considered the next step, Dr. Paller reminded the audience of the importance of presenting the benefits and risks of all the options for AD control, which could include dupilumab and immunosuppressants as initial systemic therapy.
“Many parents choose biologic treatment first, given its lack of requirement for blood monitoring and faster action than methotrexate,” Dr. Paller noted.
Nevertheless, “biologics are much more costly than immunosuppressants, require an injection – which is stressful for the child and the parents – and may not be accessible for our patients,” Dr. Paller said. Cyclosporine and methotrexate are effective and are often the best options for moderate to severe disease in areas of the world where dupilumab is not available, but Dr. Paller most commonly uses these therapies only when reimbursement for dupilumab cannot be secured, injection is not an option, or when dupilumab is not sufficiently effective and tolerated.
Providing different perspectives, the two other panelists discussing the treatment of pediatric AD also saw a role for ensuring that topical agents are not offering adequate AD control before turning to the latest and most sophisticated therapies for AD.
For meeting parent expectations when children are improving slowly on topical therapies, Peter A. Lio, MD, director of the Chicago Integrative Eczema Center and clinical assistant professor of dermatology and pediatrics at Northwestern University, suggested that integrative medicine might be helpful.
For parents not fully comfortable with standard pharmacologic agents, Dr. Lio said there is evidence to support some of the complementary approaches, and these can be reassuring to parents with an interest in alternative medicines.
In Western medicine, it is common to hear terms like “attack,” “kill,” and “suppress,” disease, but alternative therapies are generally coupled with terms like “restore,” “strengthen,” and “tonify,” he said. “Who doesn’t want to be tonified?” he asked, noting that there are many sources of data suggesting that the number of patients seeking alternative medicine is “huge.” The alternative medicines are not generally taught in medical school and remain widely ignored in typical practice, but “our patients are interested even if we are not.”
Yet, there are data to support benefit from some of these alternative therapies, providing a win-win situation for patients who derive satisfaction from nontraditional therapies alone or combined with established pharmaceutical treatments.
Of these, Dr. Lio said there is support for the use of hempseed oil as a moisturizing agent and a strategy for improving barrier function in the skin of patients with AD. In a controlled crossover study, 2 teaspoons per day of dietary hempseed oil, a product that can be purchased in some grocery stores, was associated with significant reductions in skin dryness, itchiness, and use of topical medications relative to the same amount of olive oil, he noted.
Other examples include a compress made with black tea that was associated with an anti-inflammatory effect when followed by a moisturizer, a published study asserts. Although this was a trial in adults with facial dermatitis, Dr. Lio suggested that the same anti-inflammatory effect would be anticipated for other skin conditions, including AD in children.
As a third example, Dr. Lio said topical indigo, a traditional Chinese medicine used for a variety of dermatologic conditions, including psoriasis, has also demonstrated efficacy in a randomized trial, compared with vehicle for mild to severe AD.
Complementary medicines are not for everyone, but they may have a role when managing the expectations of parents who are not fully satisfied or express concern about regimens limited to mainstream therapies alone, according to Dr. Lio. In diseases that are not curable, such as AD, he thinks this is a strategy with potential for benefit and is reassuring to patients.
Another way to avoid moving to riskier or more expensive drugs quickly is to assure patients use the drugs that were prescribed first, according to Steven R. Feldman, MD, PhD, professor of dermatology, Wake Forest University, Winston-Salem, N.C.
Dr. Feldman believes that failure to adhere to therapy is basically the fault of the medical care system, not the patient. He made an analogy to a successful piano teacher, who provides a child with sheet music and then sees the child once a week to track progress. He juxtaposed this piano teacher to one who gives the child sheet music and tells the child to come back in 10 weeks for the recital. It is not hard to guess which approach would be more effective.
“Typically, doctors are worse than that second teacher,” he said. “Doctors are like a piano teacher that does not give you the sheet music but says, ‘Here is a prescription for some sheet music. Take this prescription to the sheet music store. I have no idea how much it will cost or whether your insurance will pay for it. But once you fill this prescription for sheet music, I want you to practice this every day,’ ” he said, adding, “Practicing this sheet music may cause rashes, diarrhea, or serious infection. When the patient next comes in 10-12 weeks later and is not better, the doctor says, ‘I will give you a harder piece of sheet music and maybe two or three other instruments to practice at the same time,’ ” said Dr. Feldman, expressing why the way clinicians practice might explain much of the poor adherence problem.
This largely explains why patients with AD do not immediately respond to the therapies doctors prescribe, Dr. Feldman implied, reiterating the theme that emerged from the AD panel: Better and more options are needed for AD of the most severe types, but better management, not better drugs, is typically what is needed for most patients.
Dr. Feldman, Dr. Lio, and Dr. Paller have financial relationships with more than 30 pharmaceutical and cosmetic companies, some of which manufacture therapies for atopic dermatitis.
This article was updated July 28, 2023, to clarify the comments and viewpoints of Dr. Amy Paller.
A version of this article first appeared on Medscape.com.
ASHEVILLE, N.C. – according to a three-member expert panel mulling over strategies at the annual meeting of the Society for Pediatric Dermatology.
In introductory remarks, the three panelists briefly addressed different aspects for controlling AD, including drugs in the pipeline, the potential value of alternative therapies, and whom to blame when compliance is poor.
But panel discussion following these presentations provided an opportunity for audience engagement on practical strategies for improving AD control.
In her formal remarks prior to the panel discussion, Amy S. Paller, MD, professor of dermatology and pediatrics and chair of dermatology, Northwestern University, Chicago, and a pediatric dermatologist at the Lurie Children’s Hospital of Chicago, described emerging AD treatments. This included an update on the status of the interleukin-13 (IL-13) inhibitors tralokinumab (Adbry), which was approved by the FDA for treating AD in adults in December 2021, and lebrikizumab, which is thought likely to be soon approved in the United States on the basis of two recently published phase 3 trials.
Along with dupilumab (Dupixent) for moderate-to-severe AD in children who do not respond to optimized use of topical therapies, these new biologics appear likely to further expand choices for AD control for adults (and for kids with AD too, if eventually licensed in children), according to the data from the phase 3 studies.
During a panel discussion that followed, Stephen Gellis, MD, pediatric dermatologist and former chief of pediatric dermatology at Boston Children’s Hospital and Harvard Medical School, raised the point of optimizing tried and true topical therapies before using systemic agents. He noted that parents sometimes pressure clinicians to use a biologic – and that moving too quickly to the latest and most expensive drugs may not be necessary.
Dr. Paller acknowledged that she, like many pediatric dermatologists, employed immunosuppressants as her drugs of choice for many years – commonly starting with a few months of cyclosporine before transitioning to methotrexate, which has a delayed onset of action. In fact, she still uses this regimen in some children.
However, she now prefers dupilumab, which is the first biologic available for children in the United States with an AD indication in children as young as 6 months. She said dupilumab has fewer potential risks than cyclosporine, and it offers clinically meaningful improvement in most children. She noted that current guidelines discourage the use of systemic corticosteroids for AD in children, given their potential toxicity.
She strongly agreed with Dr. Gellis that clinicians should resist pressure to use any systemic agent if children are responding well to topical medications. In her own practice, Dr. Paller moves to systemic medications only after ensuring that there has been adherence to appropriate therapy and that there is not another diagnosis that might explain the recalcitrance to topical agents.
When a systemic medication is considered the next step, Dr. Paller reminded the audience of the importance of presenting the benefits and risks of all the options for AD control, which could include dupilumab and immunosuppressants as initial systemic therapy.
“Many parents choose biologic treatment first, given its lack of requirement for blood monitoring and faster action than methotrexate,” Dr. Paller noted.
Nevertheless, “biologics are much more costly than immunosuppressants, require an injection – which is stressful for the child and the parents – and may not be accessible for our patients,” Dr. Paller said. Cyclosporine and methotrexate are effective and are often the best options for moderate to severe disease in areas of the world where dupilumab is not available, but Dr. Paller most commonly uses these therapies only when reimbursement for dupilumab cannot be secured, injection is not an option, or when dupilumab is not sufficiently effective and tolerated.
Providing different perspectives, the two other panelists discussing the treatment of pediatric AD also saw a role for ensuring that topical agents are not offering adequate AD control before turning to the latest and most sophisticated therapies for AD.
For meeting parent expectations when children are improving slowly on topical therapies, Peter A. Lio, MD, director of the Chicago Integrative Eczema Center and clinical assistant professor of dermatology and pediatrics at Northwestern University, suggested that integrative medicine might be helpful.
For parents not fully comfortable with standard pharmacologic agents, Dr. Lio said there is evidence to support some of the complementary approaches, and these can be reassuring to parents with an interest in alternative medicines.
In Western medicine, it is common to hear terms like “attack,” “kill,” and “suppress,” disease, but alternative therapies are generally coupled with terms like “restore,” “strengthen,” and “tonify,” he said. “Who doesn’t want to be tonified?” he asked, noting that there are many sources of data suggesting that the number of patients seeking alternative medicine is “huge.” The alternative medicines are not generally taught in medical school and remain widely ignored in typical practice, but “our patients are interested even if we are not.”
Yet, there are data to support benefit from some of these alternative therapies, providing a win-win situation for patients who derive satisfaction from nontraditional therapies alone or combined with established pharmaceutical treatments.
Of these, Dr. Lio said there is support for the use of hempseed oil as a moisturizing agent and a strategy for improving barrier function in the skin of patients with AD. In a controlled crossover study, 2 teaspoons per day of dietary hempseed oil, a product that can be purchased in some grocery stores, was associated with significant reductions in skin dryness, itchiness, and use of topical medications relative to the same amount of olive oil, he noted.
Other examples include a compress made with black tea that was associated with an anti-inflammatory effect when followed by a moisturizer, a published study asserts. Although this was a trial in adults with facial dermatitis, Dr. Lio suggested that the same anti-inflammatory effect would be anticipated for other skin conditions, including AD in children.
As a third example, Dr. Lio said topical indigo, a traditional Chinese medicine used for a variety of dermatologic conditions, including psoriasis, has also demonstrated efficacy in a randomized trial, compared with vehicle for mild to severe AD.
Complementary medicines are not for everyone, but they may have a role when managing the expectations of parents who are not fully satisfied or express concern about regimens limited to mainstream therapies alone, according to Dr. Lio. In diseases that are not curable, such as AD, he thinks this is a strategy with potential for benefit and is reassuring to patients.
Another way to avoid moving to riskier or more expensive drugs quickly is to assure patients use the drugs that were prescribed first, according to Steven R. Feldman, MD, PhD, professor of dermatology, Wake Forest University, Winston-Salem, N.C.
Dr. Feldman believes that failure to adhere to therapy is basically the fault of the medical care system, not the patient. He made an analogy to a successful piano teacher, who provides a child with sheet music and then sees the child once a week to track progress. He juxtaposed this piano teacher to one who gives the child sheet music and tells the child to come back in 10 weeks for the recital. It is not hard to guess which approach would be more effective.
“Typically, doctors are worse than that second teacher,” he said. “Doctors are like a piano teacher that does not give you the sheet music but says, ‘Here is a prescription for some sheet music. Take this prescription to the sheet music store. I have no idea how much it will cost or whether your insurance will pay for it. But once you fill this prescription for sheet music, I want you to practice this every day,’ ” he said, adding, “Practicing this sheet music may cause rashes, diarrhea, or serious infection. When the patient next comes in 10-12 weeks later and is not better, the doctor says, ‘I will give you a harder piece of sheet music and maybe two or three other instruments to practice at the same time,’ ” said Dr. Feldman, expressing why the way clinicians practice might explain much of the poor adherence problem.
This largely explains why patients with AD do not immediately respond to the therapies doctors prescribe, Dr. Feldman implied, reiterating the theme that emerged from the AD panel: Better and more options are needed for AD of the most severe types, but better management, not better drugs, is typically what is needed for most patients.
Dr. Feldman, Dr. Lio, and Dr. Paller have financial relationships with more than 30 pharmaceutical and cosmetic companies, some of which manufacture therapies for atopic dermatitis.
This article was updated July 28, 2023, to clarify the comments and viewpoints of Dr. Amy Paller.
A version of this article first appeared on Medscape.com.
AT SPD 2023
Affording the cost of new obesity drugs? We can’t afford not to
SAN DIEGO – Although the glucagonlike peptide–1 (GLP-1) receptor agonists, such as liraglutide and semaglutide, have been revolutionary advances for the treatment of obesity, the cost-effectiveness of these agents for treating both obesity and type 2 diabetes remains uncertain based on published analyses.
But potential future changes in the cost-effectiveness dynamics of GLP-1 agonists could tip the balance in their favor. These include
Costs to people with obesity that are generally not part of cost-effectiveness calculations include pain, disability, depression, and bias that affect employment, Carol H. Wysham, MD, said at the recent scientific sessions of the American Diabetes Association.
Other costs to society left out of conventional calculations are items such as the incremental cost for fuel to transport a heavier population and the carbon-footprint costs for the production and transportation of the excess food produced to feed an over-fed population, added Dr. Wysham, an endocrinologist with MultiCare and the Rockwood Clinic in Spokane, Wash.
Analyses should include ‘things we don’t often think about’
“The impact of living with obesity is much greater than what we traditionally calculate in health economics,” commented Naveed Sattar, PhD, speaking from the floor during the session.
“Patient happiness and self-esteem are hard to measure and capture as cost impacts. We need to also add carbon dioxide effects and transportation costs, and governments are starting to get wise to this. How to run proper health economics analyses is the key question; we need to do better than what we currently do,” said Dr. Sattar, a professor of metabolic medicine at the University of Glasgow.
Dr. Sattar is lead author of a recent analysis that highlights the overwhelming importance of improved weight management in adults as they age to reduce their risk of developing a broad range of chronic disorders.
“Most chronic conditions are, to differing extents, caused or exacerbated by excess adiposity,” was a conclusion of his report.
“It’s important to include the costs to society, including things we don’t often think about. No one has ever done a cost analysis that includes all the factors” cited by Dr. Wysham, said Irl B. Hirsch, MD, another speaker at the session. “No one includes obstructive sleep apnea, degenerative arthritis, and the downstream effects of a high body mass index.”
The GLP-1 agonists “are great” for both weight loss and glycemic control, said Dr. Hirsch, an endocrinologist and professor at the University of Washington, Seattle. “We can’t afford not to use them. These agents have been transformational.”
U.S. has the highest drug costs
Another key factor driving cost-effectiveness is, of course, the relatively high cost of the agents in the class, especially in the United States. Dr. Hirsch cited a recently published report in Obesity that quoted monthly U.S. costs of $804 for weekly 2.4-mg injections of semaglutide (Wegovy) and $1418 for daily 3.0-mg injections of liraglutide (Saxenda). Highlighting the relatively high cost of medications in the United States, the report cited a monthly price tag of $95 for the same semaglutide regimen in Turkey and a monthly cost of $252 for the same liraglutide regimen in Norway.
U.S. prices for agents in this class may start to deflate as soon as 2024, when one or more generic versions of liraglutide are expected, following expiration of the U.S. patent later in 2023, Dr. Wysham said.
Another pending trigger for lower costs may be the possible decision by the World Health Organization to designate liraglutide an “essential medicine” later in 2023, she noted. The WHO received an application for this designation from four U.S. clinicians and is considering it as part of its planned 2023 update to the WHO’s Essential Medicines List. Dr. Wysham predicted this designation would “press international pharmaceutical companies to produce [liraglutide] at a much lower cost.”
“I’m not saying that drug companies should not profit, but they should not do it on the backs of patients,” Dr. Wysham declared. “What do we measure by ‘cost-effectiveness?’ There are so many complications of obesity. For patients with diabetes and obesity we need to look for a little different economic policy.”
Dr. Wysham has reported being an adviser to Abbott and CeQur and receiving research funding from Eli Lilly and Novo Nordisk. Dr. Hirsch has reported being a consultant for Abbott, Embecta, and Hagar, and receiving research funding from Dexcom and Insulet. Dr. Sattar has reported receiving consulting fees or speaker honoraria from Abbott Laboratories, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, MSD, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi.
A version of this article appeared on Medscape.com.
SAN DIEGO – Although the glucagonlike peptide–1 (GLP-1) receptor agonists, such as liraglutide and semaglutide, have been revolutionary advances for the treatment of obesity, the cost-effectiveness of these agents for treating both obesity and type 2 diabetes remains uncertain based on published analyses.
But potential future changes in the cost-effectiveness dynamics of GLP-1 agonists could tip the balance in their favor. These include
Costs to people with obesity that are generally not part of cost-effectiveness calculations include pain, disability, depression, and bias that affect employment, Carol H. Wysham, MD, said at the recent scientific sessions of the American Diabetes Association.
Other costs to society left out of conventional calculations are items such as the incremental cost for fuel to transport a heavier population and the carbon-footprint costs for the production and transportation of the excess food produced to feed an over-fed population, added Dr. Wysham, an endocrinologist with MultiCare and the Rockwood Clinic in Spokane, Wash.
Analyses should include ‘things we don’t often think about’
“The impact of living with obesity is much greater than what we traditionally calculate in health economics,” commented Naveed Sattar, PhD, speaking from the floor during the session.
“Patient happiness and self-esteem are hard to measure and capture as cost impacts. We need to also add carbon dioxide effects and transportation costs, and governments are starting to get wise to this. How to run proper health economics analyses is the key question; we need to do better than what we currently do,” said Dr. Sattar, a professor of metabolic medicine at the University of Glasgow.
Dr. Sattar is lead author of a recent analysis that highlights the overwhelming importance of improved weight management in adults as they age to reduce their risk of developing a broad range of chronic disorders.
“Most chronic conditions are, to differing extents, caused or exacerbated by excess adiposity,” was a conclusion of his report.
“It’s important to include the costs to society, including things we don’t often think about. No one has ever done a cost analysis that includes all the factors” cited by Dr. Wysham, said Irl B. Hirsch, MD, another speaker at the session. “No one includes obstructive sleep apnea, degenerative arthritis, and the downstream effects of a high body mass index.”
The GLP-1 agonists “are great” for both weight loss and glycemic control, said Dr. Hirsch, an endocrinologist and professor at the University of Washington, Seattle. “We can’t afford not to use them. These agents have been transformational.”
U.S. has the highest drug costs
Another key factor driving cost-effectiveness is, of course, the relatively high cost of the agents in the class, especially in the United States. Dr. Hirsch cited a recently published report in Obesity that quoted monthly U.S. costs of $804 for weekly 2.4-mg injections of semaglutide (Wegovy) and $1418 for daily 3.0-mg injections of liraglutide (Saxenda). Highlighting the relatively high cost of medications in the United States, the report cited a monthly price tag of $95 for the same semaglutide regimen in Turkey and a monthly cost of $252 for the same liraglutide regimen in Norway.
U.S. prices for agents in this class may start to deflate as soon as 2024, when one or more generic versions of liraglutide are expected, following expiration of the U.S. patent later in 2023, Dr. Wysham said.
Another pending trigger for lower costs may be the possible decision by the World Health Organization to designate liraglutide an “essential medicine” later in 2023, she noted. The WHO received an application for this designation from four U.S. clinicians and is considering it as part of its planned 2023 update to the WHO’s Essential Medicines List. Dr. Wysham predicted this designation would “press international pharmaceutical companies to produce [liraglutide] at a much lower cost.”
“I’m not saying that drug companies should not profit, but they should not do it on the backs of patients,” Dr. Wysham declared. “What do we measure by ‘cost-effectiveness?’ There are so many complications of obesity. For patients with diabetes and obesity we need to look for a little different economic policy.”
Dr. Wysham has reported being an adviser to Abbott and CeQur and receiving research funding from Eli Lilly and Novo Nordisk. Dr. Hirsch has reported being a consultant for Abbott, Embecta, and Hagar, and receiving research funding from Dexcom and Insulet. Dr. Sattar has reported receiving consulting fees or speaker honoraria from Abbott Laboratories, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, MSD, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi.
A version of this article appeared on Medscape.com.
SAN DIEGO – Although the glucagonlike peptide–1 (GLP-1) receptor agonists, such as liraglutide and semaglutide, have been revolutionary advances for the treatment of obesity, the cost-effectiveness of these agents for treating both obesity and type 2 diabetes remains uncertain based on published analyses.
But potential future changes in the cost-effectiveness dynamics of GLP-1 agonists could tip the balance in their favor. These include
Costs to people with obesity that are generally not part of cost-effectiveness calculations include pain, disability, depression, and bias that affect employment, Carol H. Wysham, MD, said at the recent scientific sessions of the American Diabetes Association.
Other costs to society left out of conventional calculations are items such as the incremental cost for fuel to transport a heavier population and the carbon-footprint costs for the production and transportation of the excess food produced to feed an over-fed population, added Dr. Wysham, an endocrinologist with MultiCare and the Rockwood Clinic in Spokane, Wash.
Analyses should include ‘things we don’t often think about’
“The impact of living with obesity is much greater than what we traditionally calculate in health economics,” commented Naveed Sattar, PhD, speaking from the floor during the session.
“Patient happiness and self-esteem are hard to measure and capture as cost impacts. We need to also add carbon dioxide effects and transportation costs, and governments are starting to get wise to this. How to run proper health economics analyses is the key question; we need to do better than what we currently do,” said Dr. Sattar, a professor of metabolic medicine at the University of Glasgow.
Dr. Sattar is lead author of a recent analysis that highlights the overwhelming importance of improved weight management in adults as they age to reduce their risk of developing a broad range of chronic disorders.
“Most chronic conditions are, to differing extents, caused or exacerbated by excess adiposity,” was a conclusion of his report.
“It’s important to include the costs to society, including things we don’t often think about. No one has ever done a cost analysis that includes all the factors” cited by Dr. Wysham, said Irl B. Hirsch, MD, another speaker at the session. “No one includes obstructive sleep apnea, degenerative arthritis, and the downstream effects of a high body mass index.”
The GLP-1 agonists “are great” for both weight loss and glycemic control, said Dr. Hirsch, an endocrinologist and professor at the University of Washington, Seattle. “We can’t afford not to use them. These agents have been transformational.”
U.S. has the highest drug costs
Another key factor driving cost-effectiveness is, of course, the relatively high cost of the agents in the class, especially in the United States. Dr. Hirsch cited a recently published report in Obesity that quoted monthly U.S. costs of $804 for weekly 2.4-mg injections of semaglutide (Wegovy) and $1418 for daily 3.0-mg injections of liraglutide (Saxenda). Highlighting the relatively high cost of medications in the United States, the report cited a monthly price tag of $95 for the same semaglutide regimen in Turkey and a monthly cost of $252 for the same liraglutide regimen in Norway.
U.S. prices for agents in this class may start to deflate as soon as 2024, when one or more generic versions of liraglutide are expected, following expiration of the U.S. patent later in 2023, Dr. Wysham said.
Another pending trigger for lower costs may be the possible decision by the World Health Organization to designate liraglutide an “essential medicine” later in 2023, she noted. The WHO received an application for this designation from four U.S. clinicians and is considering it as part of its planned 2023 update to the WHO’s Essential Medicines List. Dr. Wysham predicted this designation would “press international pharmaceutical companies to produce [liraglutide] at a much lower cost.”
“I’m not saying that drug companies should not profit, but they should not do it on the backs of patients,” Dr. Wysham declared. “What do we measure by ‘cost-effectiveness?’ There are so many complications of obesity. For patients with diabetes and obesity we need to look for a little different economic policy.”
Dr. Wysham has reported being an adviser to Abbott and CeQur and receiving research funding from Eli Lilly and Novo Nordisk. Dr. Hirsch has reported being a consultant for Abbott, Embecta, and Hagar, and receiving research funding from Dexcom and Insulet. Dr. Sattar has reported receiving consulting fees or speaker honoraria from Abbott Laboratories, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, MSD, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi.
A version of this article appeared on Medscape.com.
AT ADA 2023
Fungal cultures in bronchiectasis don’t predict outcomes
The presence of a positive fungal culture in patients with bronchiectasis does not appear to correlate with disease severity or any increased risk of an adverse outcome, according to data pulled from the Bronchiectasis and NTM Registry and presented at the 6th World Bronchiectasis & NTM Conference.
“The question we were asking is whether there is some signal that suggests we need to take care of these patients differently, and the answer is no,” reported Pamela J. McShane, MD, a pulmonologist on the faculty at the University of Texas Health Science Center at Tyler.
or more complex course than did those without a positive fungal culture.
When fungal infections are detected in an initial microbiologic evaluation of patients with bronchiectasis or other lung diseases, first-line clinicians generally assume that coverage is needed. Dr. McShane noted that many of the patients referred to her with bronchiectasis and a positive fungal culture were already on an antifungal.
These data are not supportive of treatment in the absence of fungal-related complications. Dr. McShane suggested they even raise questions about the value of culturing beyond bacterial pathogens in the absence of suspicion that fungal organisms are playing a role in symptoms. She cautioned, however, that more studies specifically studying this possibility are needed.
Study details
The data were drawn in December 2022 from the U.S.-based Bronchiectasis and NTM Registry, which at that time had 22 participating sites. Of the more than 5,000 patients enrolled, the study looked at 2,230 after several exclusions, such as a diagnosis of allergic bronchopulmonary aspergillosis (ABPA).
Of these 2,230 patients, 949 had a fungal infection at the time of diagnosis and 1,281 did not. Those with a fungal infection were further subdivided into those with an aspergillosis (331 patients) and those with a nonaspergillosis fungal infection (751 patients). The total of these two numbers is greater than the total number of fungal infections because these were not mutually exclusive.
At enrollment into the registry, there were no statistical differences between groups for age. Some statistical differences were observed among groups stratified by race, but Dr. McShane doubted that these were clinically significant with the exception of a potential disparity among Asians that might deserve further analysis.
Infection results
Of clinical features evaluated for their association with fungal infection, there was no correlation with either body mass index or history of asthma. Eosinophilia was associated significantly with positive fungal cultures.
Baseline FEV1 was slightly lower among those with a positive fungal culture even if the difference was highly significant (P = .0006). Again, Dr. McShane questioned the clinical significance of values that varied by only a few percentage points, even though she was willing to acknowledge that higher is always preferable to a lower FEV1.
In the context of other pathogens, “generally speaking, those with a positive bacterial culture were more likely to have a fungal infection,” Dr. McShane reported, although there was some variation when looking at pathogenicity of the bacteria and other variables.
“Whether this [higher rate of fungal infection] just involves the environment or our antibiotics are driving the opportunity to permit the fungi to exist, we do not have the answer,” she added.
Nontuberculosis mycobacteria (NTM) infection was similarly represented in those with or without a fungal infection, according to Dr. McShane. Noting the high use of antibiotics in an NTM population, Dr. McShane conceded that this challenges the theory that antibiotic use is driving the risk of fungal infection, but these are what the data say.
Steroid use was associated with a statistically significant risk of fungal infection, but Dr. McShane said it is unclear whether steroid use drives the risk or is an epiphenomenon.
“We looked at this a lot of different ways: oral vs. inhaled and oral vs. inhaled and oral, and it did not make much difference. Generally speaking, the fungal cultures were more likely to be positive in patients on any kind of steroid,” she said.
Finally, with the exception of the slightly lower FEV1 in patients with fungal infections, Dr. McShane said that there was no discernible relationship between the presence of a fungal infection and severity of bronchiectasis.
Because of this evidence, Dr. McShane concluded that the presence of fungus in the culture of patients with bronchiectasis does not appear to correlate with outcome or severity. Since completing the study, she said she is now using these data to reassure patients who have a positive fungal culture.
While these data do not affect the need to diagnosis fungal infections in patients who are not responding typically to therapy or otherwise have an abnormal course of bronchiectasis, raising suspicion that fungal infection is participating in the disease course, the data provide a basis for questioning whether routine cultures are needed, according to the discussion that followed Dr. McShane’s presentation.
Expert opinion
Several of the experts at the presentation provided an opinion. Some reported that they would continue to order fungal cultures on a routine basis, while others said that they now, on the basis of these data, plan to order cultures only at the first visit or when fungal infection is suspected of exacerbating the disease.
Of this latter group, which seemed to be dominant, Juzar Ali, MD, professor of medicine, Louisiana State University, New Orleans, said that he has not been ordering fungal cultures on every visit. Rather, he has been doing so selectively. Examples include those who are on steroids or those with an unusual pattern of exacerbations.
“The value of these data is that they have now provided some data to support this approach,” Dr. Ali said in an interview. Noting that this is the first large study to address this question in a systematic way, he considers this to be a valuable contribution for approaching a common clinical issue.
Dr. McShane reports no relevant financial relationships. Dr. Ali reports a financial relationship with Insmed.
A version of this article first appeared on Medscape.com.
The presence of a positive fungal culture in patients with bronchiectasis does not appear to correlate with disease severity or any increased risk of an adverse outcome, according to data pulled from the Bronchiectasis and NTM Registry and presented at the 6th World Bronchiectasis & NTM Conference.
“The question we were asking is whether there is some signal that suggests we need to take care of these patients differently, and the answer is no,” reported Pamela J. McShane, MD, a pulmonologist on the faculty at the University of Texas Health Science Center at Tyler.
or more complex course than did those without a positive fungal culture.
When fungal infections are detected in an initial microbiologic evaluation of patients with bronchiectasis or other lung diseases, first-line clinicians generally assume that coverage is needed. Dr. McShane noted that many of the patients referred to her with bronchiectasis and a positive fungal culture were already on an antifungal.
These data are not supportive of treatment in the absence of fungal-related complications. Dr. McShane suggested they even raise questions about the value of culturing beyond bacterial pathogens in the absence of suspicion that fungal organisms are playing a role in symptoms. She cautioned, however, that more studies specifically studying this possibility are needed.
Study details
The data were drawn in December 2022 from the U.S.-based Bronchiectasis and NTM Registry, which at that time had 22 participating sites. Of the more than 5,000 patients enrolled, the study looked at 2,230 after several exclusions, such as a diagnosis of allergic bronchopulmonary aspergillosis (ABPA).
Of these 2,230 patients, 949 had a fungal infection at the time of diagnosis and 1,281 did not. Those with a fungal infection were further subdivided into those with an aspergillosis (331 patients) and those with a nonaspergillosis fungal infection (751 patients). The total of these two numbers is greater than the total number of fungal infections because these were not mutually exclusive.
At enrollment into the registry, there were no statistical differences between groups for age. Some statistical differences were observed among groups stratified by race, but Dr. McShane doubted that these were clinically significant with the exception of a potential disparity among Asians that might deserve further analysis.
Infection results
Of clinical features evaluated for their association with fungal infection, there was no correlation with either body mass index or history of asthma. Eosinophilia was associated significantly with positive fungal cultures.
Baseline FEV1 was slightly lower among those with a positive fungal culture even if the difference was highly significant (P = .0006). Again, Dr. McShane questioned the clinical significance of values that varied by only a few percentage points, even though she was willing to acknowledge that higher is always preferable to a lower FEV1.
In the context of other pathogens, “generally speaking, those with a positive bacterial culture were more likely to have a fungal infection,” Dr. McShane reported, although there was some variation when looking at pathogenicity of the bacteria and other variables.
“Whether this [higher rate of fungal infection] just involves the environment or our antibiotics are driving the opportunity to permit the fungi to exist, we do not have the answer,” she added.
Nontuberculosis mycobacteria (NTM) infection was similarly represented in those with or without a fungal infection, according to Dr. McShane. Noting the high use of antibiotics in an NTM population, Dr. McShane conceded that this challenges the theory that antibiotic use is driving the risk of fungal infection, but these are what the data say.
Steroid use was associated with a statistically significant risk of fungal infection, but Dr. McShane said it is unclear whether steroid use drives the risk or is an epiphenomenon.
“We looked at this a lot of different ways: oral vs. inhaled and oral vs. inhaled and oral, and it did not make much difference. Generally speaking, the fungal cultures were more likely to be positive in patients on any kind of steroid,” she said.
Finally, with the exception of the slightly lower FEV1 in patients with fungal infections, Dr. McShane said that there was no discernible relationship between the presence of a fungal infection and severity of bronchiectasis.
Because of this evidence, Dr. McShane concluded that the presence of fungus in the culture of patients with bronchiectasis does not appear to correlate with outcome or severity. Since completing the study, she said she is now using these data to reassure patients who have a positive fungal culture.
While these data do not affect the need to diagnosis fungal infections in patients who are not responding typically to therapy or otherwise have an abnormal course of bronchiectasis, raising suspicion that fungal infection is participating in the disease course, the data provide a basis for questioning whether routine cultures are needed, according to the discussion that followed Dr. McShane’s presentation.
Expert opinion
Several of the experts at the presentation provided an opinion. Some reported that they would continue to order fungal cultures on a routine basis, while others said that they now, on the basis of these data, plan to order cultures only at the first visit or when fungal infection is suspected of exacerbating the disease.
Of this latter group, which seemed to be dominant, Juzar Ali, MD, professor of medicine, Louisiana State University, New Orleans, said that he has not been ordering fungal cultures on every visit. Rather, he has been doing so selectively. Examples include those who are on steroids or those with an unusual pattern of exacerbations.
“The value of these data is that they have now provided some data to support this approach,” Dr. Ali said in an interview. Noting that this is the first large study to address this question in a systematic way, he considers this to be a valuable contribution for approaching a common clinical issue.
Dr. McShane reports no relevant financial relationships. Dr. Ali reports a financial relationship with Insmed.
A version of this article first appeared on Medscape.com.
The presence of a positive fungal culture in patients with bronchiectasis does not appear to correlate with disease severity or any increased risk of an adverse outcome, according to data pulled from the Bronchiectasis and NTM Registry and presented at the 6th World Bronchiectasis & NTM Conference.
“The question we were asking is whether there is some signal that suggests we need to take care of these patients differently, and the answer is no,” reported Pamela J. McShane, MD, a pulmonologist on the faculty at the University of Texas Health Science Center at Tyler.
or more complex course than did those without a positive fungal culture.
When fungal infections are detected in an initial microbiologic evaluation of patients with bronchiectasis or other lung diseases, first-line clinicians generally assume that coverage is needed. Dr. McShane noted that many of the patients referred to her with bronchiectasis and a positive fungal culture were already on an antifungal.
These data are not supportive of treatment in the absence of fungal-related complications. Dr. McShane suggested they even raise questions about the value of culturing beyond bacterial pathogens in the absence of suspicion that fungal organisms are playing a role in symptoms. She cautioned, however, that more studies specifically studying this possibility are needed.
Study details
The data were drawn in December 2022 from the U.S.-based Bronchiectasis and NTM Registry, which at that time had 22 participating sites. Of the more than 5,000 patients enrolled, the study looked at 2,230 after several exclusions, such as a diagnosis of allergic bronchopulmonary aspergillosis (ABPA).
Of these 2,230 patients, 949 had a fungal infection at the time of diagnosis and 1,281 did not. Those with a fungal infection were further subdivided into those with an aspergillosis (331 patients) and those with a nonaspergillosis fungal infection (751 patients). The total of these two numbers is greater than the total number of fungal infections because these were not mutually exclusive.
At enrollment into the registry, there were no statistical differences between groups for age. Some statistical differences were observed among groups stratified by race, but Dr. McShane doubted that these were clinically significant with the exception of a potential disparity among Asians that might deserve further analysis.
Infection results
Of clinical features evaluated for their association with fungal infection, there was no correlation with either body mass index or history of asthma. Eosinophilia was associated significantly with positive fungal cultures.
Baseline FEV1 was slightly lower among those with a positive fungal culture even if the difference was highly significant (P = .0006). Again, Dr. McShane questioned the clinical significance of values that varied by only a few percentage points, even though she was willing to acknowledge that higher is always preferable to a lower FEV1.
In the context of other pathogens, “generally speaking, those with a positive bacterial culture were more likely to have a fungal infection,” Dr. McShane reported, although there was some variation when looking at pathogenicity of the bacteria and other variables.
“Whether this [higher rate of fungal infection] just involves the environment or our antibiotics are driving the opportunity to permit the fungi to exist, we do not have the answer,” she added.
Nontuberculosis mycobacteria (NTM) infection was similarly represented in those with or without a fungal infection, according to Dr. McShane. Noting the high use of antibiotics in an NTM population, Dr. McShane conceded that this challenges the theory that antibiotic use is driving the risk of fungal infection, but these are what the data say.
Steroid use was associated with a statistically significant risk of fungal infection, but Dr. McShane said it is unclear whether steroid use drives the risk or is an epiphenomenon.
“We looked at this a lot of different ways: oral vs. inhaled and oral vs. inhaled and oral, and it did not make much difference. Generally speaking, the fungal cultures were more likely to be positive in patients on any kind of steroid,” she said.
Finally, with the exception of the slightly lower FEV1 in patients with fungal infections, Dr. McShane said that there was no discernible relationship between the presence of a fungal infection and severity of bronchiectasis.
Because of this evidence, Dr. McShane concluded that the presence of fungus in the culture of patients with bronchiectasis does not appear to correlate with outcome or severity. Since completing the study, she said she is now using these data to reassure patients who have a positive fungal culture.
While these data do not affect the need to diagnosis fungal infections in patients who are not responding typically to therapy or otherwise have an abnormal course of bronchiectasis, raising suspicion that fungal infection is participating in the disease course, the data provide a basis for questioning whether routine cultures are needed, according to the discussion that followed Dr. McShane’s presentation.
Expert opinion
Several of the experts at the presentation provided an opinion. Some reported that they would continue to order fungal cultures on a routine basis, while others said that they now, on the basis of these data, plan to order cultures only at the first visit or when fungal infection is suspected of exacerbating the disease.
Of this latter group, which seemed to be dominant, Juzar Ali, MD, professor of medicine, Louisiana State University, New Orleans, said that he has not been ordering fungal cultures on every visit. Rather, he has been doing so selectively. Examples include those who are on steroids or those with an unusual pattern of exacerbations.
“The value of these data is that they have now provided some data to support this approach,” Dr. Ali said in an interview. Noting that this is the first large study to address this question in a systematic way, he considers this to be a valuable contribution for approaching a common clinical issue.
Dr. McShane reports no relevant financial relationships. Dr. Ali reports a financial relationship with Insmed.
A version of this article first appeared on Medscape.com.
Ocular complications of dermatologic treatments: Advice from a pediatric ophthalmologist
ASHEVILLE, N.C. – The, according to one of several clinical messages from a pediatric ophthalmologist who spoke at the annual meeting of the Society for Pediatric Dermatology.
“There is a lot of steroid fear out there, which you can argue is actually harmful in itself, because not treating periorbital eczema is related to a lot of eye problems, including chronic discomfort and the eye rubbing that can cause corneal abrasions and keratoconus,” said Sara Grace, MD, a pediatric ophthalmologist who is on the clinical staff at Duke University, Durham, N.C. She maintains a practice at North Carolina Eye, Ear, Nose, and Throat in Durham.
Although the risks of periorbital steroid absorption are real, a limited course of low potency topical steroids is generally adequate for common periorbital indications, and these appear to be safe.
“There is insufficient evidence to link weak periocular topical corticosteroids such as desonide or hydrocortisone with ocular complications,” said Dr. Grace, suggesting that pediatric dermatologists can be reassured when using these medications at low concentrations.
“Potent periocular steroids have been associated with ocular complications, but this has typically involved exposures over months to years,” Dr. Grace specified.
When topical corticosteroids are applied at high concentrations on the face away from the periorbital area, glaucoma and other feared ophthalmic complications cannot be entirely ruled out, but, again, the risk is low in the absence of “very large quantities” of potent topical agents applied for lengthy periods of time, according to Dr. Grace, basing this observation on case studies.
In children, as in adults, the potential exception is a child with existing ocular disease. In such cases, or in children with risk factors for ocular disease, Dr. Grace recommends referral to an ophthalmologist for a baseline examination prior to a course of topical corticosteroids with the potential of periocular absorption. With a baseline assessment, adverse effects are more easily documented if exposure is prolonged.
The message, although not identical, is similar for use of dupilumab (Dupixent) or other biologics that target the interleukin-13 (IL-13) pathway. The potential for complications cannot be ignored but these are often time-limited and the benefit is likely to exceed the risk in children who have severe atopic dermatitis or other skin conditions for which these treatments are effective.
There are several potential mechanisms by which biologics targeting IL-13 might increase risk of ocular complications, one of which is the role that IL-13 plays in ocular mucus production, regulation of conjunctival goblet cells, and tear production, according to several published reports.
“Up to 30% of children will get some type of eye complication but, fortunately, most of them will not have to stop therapy,” Dr. Grace said. These side effects include conjunctivitis, blepharitis, keratitis, dry eye, and itching, but they are typically manageable. Topical steroids or calcineurin inhibitors can be offered if needed, but many of these conditions will self-resolve. Dr. Grace estimated that less than 1% of patients need to stop treatment because of ophthalmic side effects.
Lesions that obstruct vision
Dr. Grace urged pediatric dermatologists to be aware of the risk for amblyopia in young children with lesions that obstruct vision in one eye. In early development, prolonged obstruction of vision in one eye can alter neural communication with the brain, producing permanent vision impairment.
She explained that clearing the obstructed vision, whether from a capillary hemangioma or any periorbital growth, should be considered urgent to avoid irreversible damage.
Similarly, periorbital port-wine stains associated with Sturge-Weber syndrome, which is primarily a vascular disorder that predisposes children to glaucoma, represents a condition that requires prompt attention. Sturge-Weber syndrome is often but not always identified at birth, but it is a condition for which evaluation and treatment should involve the participation of an ophthalmologist.
Meibomian gland disease is another disorder that is often seen first by a pediatric dermatologist but also requires collaborative management. The challenge is sorting out the underlying cause or causes and initiating a therapy that unclogs the gland without having to resort to incision and drainage.
“Drainage is hard to do and is not necessarily effective,” explained Dr. Grace. While scrubs, warmth, and massage frequently are adequate to unclog the gland – which secretes meibum, a complex of lipids that perform several functions in protecting the eye – therapies specific to the cause, such as Demodex-related blepharitis, chalazions, and styes, might be needed.
Dr. Grace indicated that patience is often needed. The process of unclogging these glands often takes time, but she emphasized that a first-line conservative approach is always appropriate to avoid the difficulty and potential problems of incisions.
In general, these messages are not novel, but they provide a refresher for pediatric dermatologists who do not regularly confront complications that involve the eyes. According to session moderator, Elizabeth Neiman, MD, assistant professor of pediatric dermatology, University of North Carolina at Chapel Hill, the messages regarding topical steroids on the face and the eyes are “important” and worth emphasizing.
“It’s useful to reinforce the point that corticosteroids should be used when needed in the periorbital area [to control skin diseases] if they are used in low concentrations,” Dr. Neiman told this news organization.
Similarly, conjunctivitis and other ocular complications of dupilumab are a source of concern for parents as well as dermatologists. Dr. Neiman indicated that a review of the benefit-to-risk ratio is important when considering these treatments in patients with indications for severe skin disorders.
Dr. Grace and Dr. Nieman have no potential financial conflicts related to this topic.
A version of this article first appeared on Medscape.com.
ASHEVILLE, N.C. – The, according to one of several clinical messages from a pediatric ophthalmologist who spoke at the annual meeting of the Society for Pediatric Dermatology.
“There is a lot of steroid fear out there, which you can argue is actually harmful in itself, because not treating periorbital eczema is related to a lot of eye problems, including chronic discomfort and the eye rubbing that can cause corneal abrasions and keratoconus,” said Sara Grace, MD, a pediatric ophthalmologist who is on the clinical staff at Duke University, Durham, N.C. She maintains a practice at North Carolina Eye, Ear, Nose, and Throat in Durham.
Although the risks of periorbital steroid absorption are real, a limited course of low potency topical steroids is generally adequate for common periorbital indications, and these appear to be safe.
“There is insufficient evidence to link weak periocular topical corticosteroids such as desonide or hydrocortisone with ocular complications,” said Dr. Grace, suggesting that pediatric dermatologists can be reassured when using these medications at low concentrations.
“Potent periocular steroids have been associated with ocular complications, but this has typically involved exposures over months to years,” Dr. Grace specified.
When topical corticosteroids are applied at high concentrations on the face away from the periorbital area, glaucoma and other feared ophthalmic complications cannot be entirely ruled out, but, again, the risk is low in the absence of “very large quantities” of potent topical agents applied for lengthy periods of time, according to Dr. Grace, basing this observation on case studies.
In children, as in adults, the potential exception is a child with existing ocular disease. In such cases, or in children with risk factors for ocular disease, Dr. Grace recommends referral to an ophthalmologist for a baseline examination prior to a course of topical corticosteroids with the potential of periocular absorption. With a baseline assessment, adverse effects are more easily documented if exposure is prolonged.
The message, although not identical, is similar for use of dupilumab (Dupixent) or other biologics that target the interleukin-13 (IL-13) pathway. The potential for complications cannot be ignored but these are often time-limited and the benefit is likely to exceed the risk in children who have severe atopic dermatitis or other skin conditions for which these treatments are effective.
There are several potential mechanisms by which biologics targeting IL-13 might increase risk of ocular complications, one of which is the role that IL-13 plays in ocular mucus production, regulation of conjunctival goblet cells, and tear production, according to several published reports.
“Up to 30% of children will get some type of eye complication but, fortunately, most of them will not have to stop therapy,” Dr. Grace said. These side effects include conjunctivitis, blepharitis, keratitis, dry eye, and itching, but they are typically manageable. Topical steroids or calcineurin inhibitors can be offered if needed, but many of these conditions will self-resolve. Dr. Grace estimated that less than 1% of patients need to stop treatment because of ophthalmic side effects.
Lesions that obstruct vision
Dr. Grace urged pediatric dermatologists to be aware of the risk for amblyopia in young children with lesions that obstruct vision in one eye. In early development, prolonged obstruction of vision in one eye can alter neural communication with the brain, producing permanent vision impairment.
She explained that clearing the obstructed vision, whether from a capillary hemangioma or any periorbital growth, should be considered urgent to avoid irreversible damage.
Similarly, periorbital port-wine stains associated with Sturge-Weber syndrome, which is primarily a vascular disorder that predisposes children to glaucoma, represents a condition that requires prompt attention. Sturge-Weber syndrome is often but not always identified at birth, but it is a condition for which evaluation and treatment should involve the participation of an ophthalmologist.
Meibomian gland disease is another disorder that is often seen first by a pediatric dermatologist but also requires collaborative management. The challenge is sorting out the underlying cause or causes and initiating a therapy that unclogs the gland without having to resort to incision and drainage.
“Drainage is hard to do and is not necessarily effective,” explained Dr. Grace. While scrubs, warmth, and massage frequently are adequate to unclog the gland – which secretes meibum, a complex of lipids that perform several functions in protecting the eye – therapies specific to the cause, such as Demodex-related blepharitis, chalazions, and styes, might be needed.
Dr. Grace indicated that patience is often needed. The process of unclogging these glands often takes time, but she emphasized that a first-line conservative approach is always appropriate to avoid the difficulty and potential problems of incisions.
In general, these messages are not novel, but they provide a refresher for pediatric dermatologists who do not regularly confront complications that involve the eyes. According to session moderator, Elizabeth Neiman, MD, assistant professor of pediatric dermatology, University of North Carolina at Chapel Hill, the messages regarding topical steroids on the face and the eyes are “important” and worth emphasizing.
“It’s useful to reinforce the point that corticosteroids should be used when needed in the periorbital area [to control skin diseases] if they are used in low concentrations,” Dr. Neiman told this news organization.
Similarly, conjunctivitis and other ocular complications of dupilumab are a source of concern for parents as well as dermatologists. Dr. Neiman indicated that a review of the benefit-to-risk ratio is important when considering these treatments in patients with indications for severe skin disorders.
Dr. Grace and Dr. Nieman have no potential financial conflicts related to this topic.
A version of this article first appeared on Medscape.com.
ASHEVILLE, N.C. – The, according to one of several clinical messages from a pediatric ophthalmologist who spoke at the annual meeting of the Society for Pediatric Dermatology.
“There is a lot of steroid fear out there, which you can argue is actually harmful in itself, because not treating periorbital eczema is related to a lot of eye problems, including chronic discomfort and the eye rubbing that can cause corneal abrasions and keratoconus,” said Sara Grace, MD, a pediatric ophthalmologist who is on the clinical staff at Duke University, Durham, N.C. She maintains a practice at North Carolina Eye, Ear, Nose, and Throat in Durham.
Although the risks of periorbital steroid absorption are real, a limited course of low potency topical steroids is generally adequate for common periorbital indications, and these appear to be safe.
“There is insufficient evidence to link weak periocular topical corticosteroids such as desonide or hydrocortisone with ocular complications,” said Dr. Grace, suggesting that pediatric dermatologists can be reassured when using these medications at low concentrations.
“Potent periocular steroids have been associated with ocular complications, but this has typically involved exposures over months to years,” Dr. Grace specified.
When topical corticosteroids are applied at high concentrations on the face away from the periorbital area, glaucoma and other feared ophthalmic complications cannot be entirely ruled out, but, again, the risk is low in the absence of “very large quantities” of potent topical agents applied for lengthy periods of time, according to Dr. Grace, basing this observation on case studies.
In children, as in adults, the potential exception is a child with existing ocular disease. In such cases, or in children with risk factors for ocular disease, Dr. Grace recommends referral to an ophthalmologist for a baseline examination prior to a course of topical corticosteroids with the potential of periocular absorption. With a baseline assessment, adverse effects are more easily documented if exposure is prolonged.
The message, although not identical, is similar for use of dupilumab (Dupixent) or other biologics that target the interleukin-13 (IL-13) pathway. The potential for complications cannot be ignored but these are often time-limited and the benefit is likely to exceed the risk in children who have severe atopic dermatitis or other skin conditions for which these treatments are effective.
There are several potential mechanisms by which biologics targeting IL-13 might increase risk of ocular complications, one of which is the role that IL-13 plays in ocular mucus production, regulation of conjunctival goblet cells, and tear production, according to several published reports.
“Up to 30% of children will get some type of eye complication but, fortunately, most of them will not have to stop therapy,” Dr. Grace said. These side effects include conjunctivitis, blepharitis, keratitis, dry eye, and itching, but they are typically manageable. Topical steroids or calcineurin inhibitors can be offered if needed, but many of these conditions will self-resolve. Dr. Grace estimated that less than 1% of patients need to stop treatment because of ophthalmic side effects.
Lesions that obstruct vision
Dr. Grace urged pediatric dermatologists to be aware of the risk for amblyopia in young children with lesions that obstruct vision in one eye. In early development, prolonged obstruction of vision in one eye can alter neural communication with the brain, producing permanent vision impairment.
She explained that clearing the obstructed vision, whether from a capillary hemangioma or any periorbital growth, should be considered urgent to avoid irreversible damage.
Similarly, periorbital port-wine stains associated with Sturge-Weber syndrome, which is primarily a vascular disorder that predisposes children to glaucoma, represents a condition that requires prompt attention. Sturge-Weber syndrome is often but not always identified at birth, but it is a condition for which evaluation and treatment should involve the participation of an ophthalmologist.
Meibomian gland disease is another disorder that is often seen first by a pediatric dermatologist but also requires collaborative management. The challenge is sorting out the underlying cause or causes and initiating a therapy that unclogs the gland without having to resort to incision and drainage.
“Drainage is hard to do and is not necessarily effective,” explained Dr. Grace. While scrubs, warmth, and massage frequently are adequate to unclog the gland – which secretes meibum, a complex of lipids that perform several functions in protecting the eye – therapies specific to the cause, such as Demodex-related blepharitis, chalazions, and styes, might be needed.
Dr. Grace indicated that patience is often needed. The process of unclogging these glands often takes time, but she emphasized that a first-line conservative approach is always appropriate to avoid the difficulty and potential problems of incisions.
In general, these messages are not novel, but they provide a refresher for pediatric dermatologists who do not regularly confront complications that involve the eyes. According to session moderator, Elizabeth Neiman, MD, assistant professor of pediatric dermatology, University of North Carolina at Chapel Hill, the messages regarding topical steroids on the face and the eyes are “important” and worth emphasizing.
“It’s useful to reinforce the point that corticosteroids should be used when needed in the periorbital area [to control skin diseases] if they are used in low concentrations,” Dr. Neiman told this news organization.
Similarly, conjunctivitis and other ocular complications of dupilumab are a source of concern for parents as well as dermatologists. Dr. Neiman indicated that a review of the benefit-to-risk ratio is important when considering these treatments in patients with indications for severe skin disorders.
Dr. Grace and Dr. Nieman have no potential financial conflicts related to this topic.
A version of this article first appeared on Medscape.com.
AT SPD 2023
Asthma severity, exacerbations increase with RV infection
TOPLINE:
Immunological and quantitative mRNA assays support a pathogenesis role for histamine-releasing factor (HRF), its interaction with HRF-reactive immunoglobulin E and rhinovirus (RV) in asthma severity and exacerbation.
METHODOLOGY:
- Clinical data for healthy controls (HCs) were compared with data from patients with asthma for three distinct cohorts recruited from programs located in Pittsburg, Boston, and Virginia.
- Cohorts differed primarily by total number of participants, median age, description of asthma severity, RV status, and longitudinal follow-up.
- Enzyme-linked immunoassay tests quantified for comparisons total IgE, IgGs, and IgG1 levels occurring in human sera samples and for HRF-reactive IgE, IgG1, and IgG2b in sera from mice inoculated with mouse .
- Anti-IgE stimulation experiments characterized bronchoalveolar lavage (BAL) cell supernatants for tryptase and PGD2 by ELISA and the mRNAs for tryptase and FCER1A
- Effect of inoculated RV infections and/or house dust mite allergen on stimulating HRF secretion from respiratory epithelial cells and in vitro–grown lung BEAS-2B cells was evaluated by Western blots.
TAKEAWAY:
- HRF-reactive IgGs and IgG1 levels in serum were lower in people with asthma than in HCs.
- People with asthma with high HRF-reactive IgE, compared with those with low levels, tended to release more tryptase prostaglandin D2 with anti-IgE stimulation of BAL cells.
- RV infection induced HFR secretions from both in vivo– and in vitro–grown respiratory epithelial cells and was associated with higher levels of HRF-IgE at the time of asthma exacerbations, compared with after resolution.
IN PRACTICE:
Inhibiting HRF and HRF-reactive IgE interactions “can be a preventative/therapeutic target” for severe and RV-induced exacerbated asthma conditions.
SOURCE:
The study led by Yu Kawakami, MD, of La Jolla Institute for Allergy & Immunology, California, and colleagues was published in the Journal of Allergy and Clinical Immunology
LIMITATIONS:
Small sample sizes, large median age differences between cohorts, and lack of data for other demographic traits and variant asthma phenotypes or endotypes in some cohorts are noted limitations that may affect result extrapolations and conclusions.
DISCLOSURES:
The authors report there are no conflicts of interest directly related to this study.
A version of this article first appeared on Medscape.com.
TOPLINE:
Immunological and quantitative mRNA assays support a pathogenesis role for histamine-releasing factor (HRF), its interaction with HRF-reactive immunoglobulin E and rhinovirus (RV) in asthma severity and exacerbation.
METHODOLOGY:
- Clinical data for healthy controls (HCs) were compared with data from patients with asthma for three distinct cohorts recruited from programs located in Pittsburg, Boston, and Virginia.
- Cohorts differed primarily by total number of participants, median age, description of asthma severity, RV status, and longitudinal follow-up.
- Enzyme-linked immunoassay tests quantified for comparisons total IgE, IgGs, and IgG1 levels occurring in human sera samples and for HRF-reactive IgE, IgG1, and IgG2b in sera from mice inoculated with mouse .
- Anti-IgE stimulation experiments characterized bronchoalveolar lavage (BAL) cell supernatants for tryptase and PGD2 by ELISA and the mRNAs for tryptase and FCER1A
- Effect of inoculated RV infections and/or house dust mite allergen on stimulating HRF secretion from respiratory epithelial cells and in vitro–grown lung BEAS-2B cells was evaluated by Western blots.
TAKEAWAY:
- HRF-reactive IgGs and IgG1 levels in serum were lower in people with asthma than in HCs.
- People with asthma with high HRF-reactive IgE, compared with those with low levels, tended to release more tryptase prostaglandin D2 with anti-IgE stimulation of BAL cells.
- RV infection induced HFR secretions from both in vivo– and in vitro–grown respiratory epithelial cells and was associated with higher levels of HRF-IgE at the time of asthma exacerbations, compared with after resolution.
IN PRACTICE:
Inhibiting HRF and HRF-reactive IgE interactions “can be a preventative/therapeutic target” for severe and RV-induced exacerbated asthma conditions.
SOURCE:
The study led by Yu Kawakami, MD, of La Jolla Institute for Allergy & Immunology, California, and colleagues was published in the Journal of Allergy and Clinical Immunology
LIMITATIONS:
Small sample sizes, large median age differences between cohorts, and lack of data for other demographic traits and variant asthma phenotypes or endotypes in some cohorts are noted limitations that may affect result extrapolations and conclusions.
DISCLOSURES:
The authors report there are no conflicts of interest directly related to this study.
A version of this article first appeared on Medscape.com.
TOPLINE:
Immunological and quantitative mRNA assays support a pathogenesis role for histamine-releasing factor (HRF), its interaction with HRF-reactive immunoglobulin E and rhinovirus (RV) in asthma severity and exacerbation.
METHODOLOGY:
- Clinical data for healthy controls (HCs) were compared with data from patients with asthma for three distinct cohorts recruited from programs located in Pittsburg, Boston, and Virginia.
- Cohorts differed primarily by total number of participants, median age, description of asthma severity, RV status, and longitudinal follow-up.
- Enzyme-linked immunoassay tests quantified for comparisons total IgE, IgGs, and IgG1 levels occurring in human sera samples and for HRF-reactive IgE, IgG1, and IgG2b in sera from mice inoculated with mouse .
- Anti-IgE stimulation experiments characterized bronchoalveolar lavage (BAL) cell supernatants for tryptase and PGD2 by ELISA and the mRNAs for tryptase and FCER1A
- Effect of inoculated RV infections and/or house dust mite allergen on stimulating HRF secretion from respiratory epithelial cells and in vitro–grown lung BEAS-2B cells was evaluated by Western blots.
TAKEAWAY:
- HRF-reactive IgGs and IgG1 levels in serum were lower in people with asthma than in HCs.
- People with asthma with high HRF-reactive IgE, compared with those with low levels, tended to release more tryptase prostaglandin D2 with anti-IgE stimulation of BAL cells.
- RV infection induced HFR secretions from both in vivo– and in vitro–grown respiratory epithelial cells and was associated with higher levels of HRF-IgE at the time of asthma exacerbations, compared with after resolution.
IN PRACTICE:
Inhibiting HRF and HRF-reactive IgE interactions “can be a preventative/therapeutic target” for severe and RV-induced exacerbated asthma conditions.
SOURCE:
The study led by Yu Kawakami, MD, of La Jolla Institute for Allergy & Immunology, California, and colleagues was published in the Journal of Allergy and Clinical Immunology
LIMITATIONS:
Small sample sizes, large median age differences between cohorts, and lack of data for other demographic traits and variant asthma phenotypes or endotypes in some cohorts are noted limitations that may affect result extrapolations and conclusions.
DISCLOSURES:
The authors report there are no conflicts of interest directly related to this study.
A version of this article first appeared on Medscape.com.
Rising patient costs tied to private equity ownership
The report was a collaboration of University of California, Berkeley, staff and researchers from two nonprofits, the American Antitrust Institute and the Washington Center for Equitable Growth. It provides “convincing evidence that incentives to put profits before patients have grown stronger with an increase in private equity ownership of physician practices,” lead author Richard Scheffler, PhD, of UC Berkeley said in a statement.
The report also noted that private equity acquisitions of physician groups have risen sixfold in just a decade, increasing from 75 deals in 2012 to 484 deals in 2021.
Separately, the American Medical Association earlier released a separate report on trends in physician practice arrangements, finding that the percentage of physicians working in private equity–owned groups was 4.5% in 2022, the same as in its previous 2020 report. The share of physicians working in private practices fell by 13 percentage points from 60.1% to 46.7% between 2012 and 2022, the AMA reported.
The Berkeley report and the AMA update come amid rising concerns about the effects of the decline of independent physician practices. The U.S. Senate Finance Committee, which oversees most federal health spending, held a June hearing examining the causes and consequences of increased corporate ownership in health care, including a look at physician practices.
“It’s increasingly clear that consolidation in health care is not lowering costs or increasing the quality of Americans’ health care,” Senate Finance Chairman Ron Wyden (D-Ore.) said in an email. “For private equity in health care in particular, there needs to be more transparency around ownership so the effect on these business relationships can be better understood.”
Federal and state agencies do not generally track acquisitions of physician practices.
The UC Berkeley report impressively documents the rising influence of private equity in health care, for which it’s tough to find good data, said Karen Joynt Maddox, MD, MPH, of Washington University in St. Louis. Dr. Maddox, a cardiologist and policy researcher who also has studied the effects of consolidation in health care, examined the new report at the request of this news organization.
“They did a great job with the data,” Dr. Maddox said. “One of the big issues around private equity, and in general, ‘corporatization’ and consolidation of health care, is that there’s not a great way to track ownership changes. It’s really difficult to study.”
Dr. Scheffler and colleagues used data from the commercial firm PitchBook to identify acquisitions of physician practices by private equity firms. They consulted IQVIA’s physician databases – OneKey and SK&A Office-Based Physicians Database – to learn about the location, size, and specialties of acquired practices. They also used data from the nonprofit Health Care Cost Institute, which tracks commercial health plan claims, to assess how private equity acquisitions affected prices.
The researchers then matched the findings for practices acquired by private equity firms from 2015 to 2021 against those for comparable physician practices that remained independent from 2012 to 2021.
The authors then tied private-equity ownership to the following price increases:
- Gastroenterology (14%; 95% confidence interval, 7.9%-20.4%
- Oncology (16.4%; 95% CI, 5.5%-28.4%)
- Dermatology (4.0%; 95% CI, 1%-7.1%)
- Ob.gyn. (8.8%; 95% CI, 3.8%-14%)
- Ophthalmology (8.7%; 95% CI, 5.1%-12.3%)
- Radiology (8.2%; 95% CI, 0.8%-16.1%)
- Orthopedics (7.1%; 95% CI, 2.2%-12.3%)
- Primary care (4.1%; 95% CI, 1.3%-7%)
The analysis also found higher prices for cardiology (8.7%; 95% CI, –6.4% to 26.1%) and urology (4.2%; 95% CI, –2.3% to 11.1%), but neither of these findings was statistically significant, one of the authors, Daniel R. Arnold, PhD, of UC Berkeley, said in an email. This was most likely caused by smaller sample sizes for these fields.
Factors driving consolidation
The two reports and the Senate Finance consolidation hearing raised similar issues, including calls to look at the factors driving more physicians out of independent practice, including Medicare reimbursement that may not keep up with rising inflation.
The Berkeley report authors called for Congress to add a broad inflation component to the Medicare physician fee schedule. It also called on Congress to add cases where Medicare, the biggest U.S. purchaser of health care, pays less for services when performed in independent practices than in hospital-affiliated ones.
Shawn Martin, executive vice president and CEO of the American Academy of Family Physicians, said his group appreciates how the report from UC Berkeley and nonprofit groups echoed recommendations many clinicians have made, including the call for a broad inflation adjustment for the fee schedule.
“To move the needle forward, Congress must advance site-neutral payment policies while also addressing the administrative requirements that take physicians away from the important work of caring for patients,” Mr. Martin said in an email.
Arnold Ventures provided funding for the report, which was a joint project of the American Antitrust Institute, the Nicholas C. Petris Center on Health Care Markets and Consumer Welfare, UC Berkeley, and the Washington Center for Equitable Growth.
A version of this article appeared on Medscape.com.
The report was a collaboration of University of California, Berkeley, staff and researchers from two nonprofits, the American Antitrust Institute and the Washington Center for Equitable Growth. It provides “convincing evidence that incentives to put profits before patients have grown stronger with an increase in private equity ownership of physician practices,” lead author Richard Scheffler, PhD, of UC Berkeley said in a statement.
The report also noted that private equity acquisitions of physician groups have risen sixfold in just a decade, increasing from 75 deals in 2012 to 484 deals in 2021.
Separately, the American Medical Association earlier released a separate report on trends in physician practice arrangements, finding that the percentage of physicians working in private equity–owned groups was 4.5% in 2022, the same as in its previous 2020 report. The share of physicians working in private practices fell by 13 percentage points from 60.1% to 46.7% between 2012 and 2022, the AMA reported.
The Berkeley report and the AMA update come amid rising concerns about the effects of the decline of independent physician practices. The U.S. Senate Finance Committee, which oversees most federal health spending, held a June hearing examining the causes and consequences of increased corporate ownership in health care, including a look at physician practices.
“It’s increasingly clear that consolidation in health care is not lowering costs or increasing the quality of Americans’ health care,” Senate Finance Chairman Ron Wyden (D-Ore.) said in an email. “For private equity in health care in particular, there needs to be more transparency around ownership so the effect on these business relationships can be better understood.”
Federal and state agencies do not generally track acquisitions of physician practices.
The UC Berkeley report impressively documents the rising influence of private equity in health care, for which it’s tough to find good data, said Karen Joynt Maddox, MD, MPH, of Washington University in St. Louis. Dr. Maddox, a cardiologist and policy researcher who also has studied the effects of consolidation in health care, examined the new report at the request of this news organization.
“They did a great job with the data,” Dr. Maddox said. “One of the big issues around private equity, and in general, ‘corporatization’ and consolidation of health care, is that there’s not a great way to track ownership changes. It’s really difficult to study.”
Dr. Scheffler and colleagues used data from the commercial firm PitchBook to identify acquisitions of physician practices by private equity firms. They consulted IQVIA’s physician databases – OneKey and SK&A Office-Based Physicians Database – to learn about the location, size, and specialties of acquired practices. They also used data from the nonprofit Health Care Cost Institute, which tracks commercial health plan claims, to assess how private equity acquisitions affected prices.
The researchers then matched the findings for practices acquired by private equity firms from 2015 to 2021 against those for comparable physician practices that remained independent from 2012 to 2021.
The authors then tied private-equity ownership to the following price increases:
- Gastroenterology (14%; 95% confidence interval, 7.9%-20.4%
- Oncology (16.4%; 95% CI, 5.5%-28.4%)
- Dermatology (4.0%; 95% CI, 1%-7.1%)
- Ob.gyn. (8.8%; 95% CI, 3.8%-14%)
- Ophthalmology (8.7%; 95% CI, 5.1%-12.3%)
- Radiology (8.2%; 95% CI, 0.8%-16.1%)
- Orthopedics (7.1%; 95% CI, 2.2%-12.3%)
- Primary care (4.1%; 95% CI, 1.3%-7%)
The analysis also found higher prices for cardiology (8.7%; 95% CI, –6.4% to 26.1%) and urology (4.2%; 95% CI, –2.3% to 11.1%), but neither of these findings was statistically significant, one of the authors, Daniel R. Arnold, PhD, of UC Berkeley, said in an email. This was most likely caused by smaller sample sizes for these fields.
Factors driving consolidation
The two reports and the Senate Finance consolidation hearing raised similar issues, including calls to look at the factors driving more physicians out of independent practice, including Medicare reimbursement that may not keep up with rising inflation.
The Berkeley report authors called for Congress to add a broad inflation component to the Medicare physician fee schedule. It also called on Congress to add cases where Medicare, the biggest U.S. purchaser of health care, pays less for services when performed in independent practices than in hospital-affiliated ones.
Shawn Martin, executive vice president and CEO of the American Academy of Family Physicians, said his group appreciates how the report from UC Berkeley and nonprofit groups echoed recommendations many clinicians have made, including the call for a broad inflation adjustment for the fee schedule.
“To move the needle forward, Congress must advance site-neutral payment policies while also addressing the administrative requirements that take physicians away from the important work of caring for patients,” Mr. Martin said in an email.
Arnold Ventures provided funding for the report, which was a joint project of the American Antitrust Institute, the Nicholas C. Petris Center on Health Care Markets and Consumer Welfare, UC Berkeley, and the Washington Center for Equitable Growth.
A version of this article appeared on Medscape.com.
The report was a collaboration of University of California, Berkeley, staff and researchers from two nonprofits, the American Antitrust Institute and the Washington Center for Equitable Growth. It provides “convincing evidence that incentives to put profits before patients have grown stronger with an increase in private equity ownership of physician practices,” lead author Richard Scheffler, PhD, of UC Berkeley said in a statement.
The report also noted that private equity acquisitions of physician groups have risen sixfold in just a decade, increasing from 75 deals in 2012 to 484 deals in 2021.
Separately, the American Medical Association earlier released a separate report on trends in physician practice arrangements, finding that the percentage of physicians working in private equity–owned groups was 4.5% in 2022, the same as in its previous 2020 report. The share of physicians working in private practices fell by 13 percentage points from 60.1% to 46.7% between 2012 and 2022, the AMA reported.
The Berkeley report and the AMA update come amid rising concerns about the effects of the decline of independent physician practices. The U.S. Senate Finance Committee, which oversees most federal health spending, held a June hearing examining the causes and consequences of increased corporate ownership in health care, including a look at physician practices.
“It’s increasingly clear that consolidation in health care is not lowering costs or increasing the quality of Americans’ health care,” Senate Finance Chairman Ron Wyden (D-Ore.) said in an email. “For private equity in health care in particular, there needs to be more transparency around ownership so the effect on these business relationships can be better understood.”
Federal and state agencies do not generally track acquisitions of physician practices.
The UC Berkeley report impressively documents the rising influence of private equity in health care, for which it’s tough to find good data, said Karen Joynt Maddox, MD, MPH, of Washington University in St. Louis. Dr. Maddox, a cardiologist and policy researcher who also has studied the effects of consolidation in health care, examined the new report at the request of this news organization.
“They did a great job with the data,” Dr. Maddox said. “One of the big issues around private equity, and in general, ‘corporatization’ and consolidation of health care, is that there’s not a great way to track ownership changes. It’s really difficult to study.”
Dr. Scheffler and colleagues used data from the commercial firm PitchBook to identify acquisitions of physician practices by private equity firms. They consulted IQVIA’s physician databases – OneKey and SK&A Office-Based Physicians Database – to learn about the location, size, and specialties of acquired practices. They also used data from the nonprofit Health Care Cost Institute, which tracks commercial health plan claims, to assess how private equity acquisitions affected prices.
The researchers then matched the findings for practices acquired by private equity firms from 2015 to 2021 against those for comparable physician practices that remained independent from 2012 to 2021.
The authors then tied private-equity ownership to the following price increases:
- Gastroenterology (14%; 95% confidence interval, 7.9%-20.4%
- Oncology (16.4%; 95% CI, 5.5%-28.4%)
- Dermatology (4.0%; 95% CI, 1%-7.1%)
- Ob.gyn. (8.8%; 95% CI, 3.8%-14%)
- Ophthalmology (8.7%; 95% CI, 5.1%-12.3%)
- Radiology (8.2%; 95% CI, 0.8%-16.1%)
- Orthopedics (7.1%; 95% CI, 2.2%-12.3%)
- Primary care (4.1%; 95% CI, 1.3%-7%)
The analysis also found higher prices for cardiology (8.7%; 95% CI, –6.4% to 26.1%) and urology (4.2%; 95% CI, –2.3% to 11.1%), but neither of these findings was statistically significant, one of the authors, Daniel R. Arnold, PhD, of UC Berkeley, said in an email. This was most likely caused by smaller sample sizes for these fields.
Factors driving consolidation
The two reports and the Senate Finance consolidation hearing raised similar issues, including calls to look at the factors driving more physicians out of independent practice, including Medicare reimbursement that may not keep up with rising inflation.
The Berkeley report authors called for Congress to add a broad inflation component to the Medicare physician fee schedule. It also called on Congress to add cases where Medicare, the biggest U.S. purchaser of health care, pays less for services when performed in independent practices than in hospital-affiliated ones.
Shawn Martin, executive vice president and CEO of the American Academy of Family Physicians, said his group appreciates how the report from UC Berkeley and nonprofit groups echoed recommendations many clinicians have made, including the call for a broad inflation adjustment for the fee schedule.
“To move the needle forward, Congress must advance site-neutral payment policies while also addressing the administrative requirements that take physicians away from the important work of caring for patients,” Mr. Martin said in an email.
Arnold Ventures provided funding for the report, which was a joint project of the American Antitrust Institute, the Nicholas C. Petris Center on Health Care Markets and Consumer Welfare, UC Berkeley, and the Washington Center for Equitable Growth.
A version of this article appeared on Medscape.com.
FDA approves quizartinib for newly diagnosed AML
On July 20 the FDA also approved the LeukoStrat CDx FLT3 Mutation Assay to determine whether patients have this mutation.
The agency granted quizartinib a first-line indication for use in combination with standard chemotherapy – cytarabine and anthracycline induction followed by cytarabine consolidation – and as maintenance monotherapy afterwards, in adults whose tumors express FLT3-ITD.
The FLT3 protein is a tyrosine kinase receptor found on hematopoietic stem cells. Wild-type FLT3 promotes cell survival, growth, and differentiation, but ITD (internal tandem duplication)-mutated FLT3, which quizartinib targets, is associated with a higher relapse risk and shorter survival. About a quarter of AML patients carry the mutation.
Approval was based on the phase 3 QuANTUM-First trial in over 500 patients with the mutation. Median overall survival among patients on standard chemotherapy randomly assigned to quizartinib was 31.9 months versus 15.1 months in patients randomly assigned to placebo, a 22.4% reduction in the risk of death (P = .0324).
Quizartinib is not indicated as maintenance monotherapy after allogeneic hematopoietic stem cell transplantation.
In a company press release, the drug’s manufacturer Daiichi Sankyo said quizartinib will be available in the United States soon.
Company executive Ken Takeshita, MD, called the approval “an important milestone, as patients with the FLT3-ITD subtype of AML can now be treated with the first-ever FLT3 inhibitor approved across the three phases of treatment these patients typically receive.”
The FDA’s original decision date was April 24, but the agency pushed it back 3 months to review updates Daiichi Sankyo made to quizartinib’s Risk Evaluation and Mitigation Strategies (REMS) program in response to an agency request.
Quizartinib carries a boxed warning of QT prolongation, torsades de pointes, and cardiac arrest. Because of these risks, it’s only available through a new program, dubbed “Vanflyta REMS.”
In the trial, the most common adverse with quizartinib included lymphopenia (60%), hypokalemia (59%), hypoalbuminemia (53%), hypophosphatemia (52%), alkaline phosphatase increased (51%), hypomagnesemia (44%), febrile neutropenia (44%), diarrhea (42%), mucositis (38%), nausea (34%), and hypocalcemia (33%), among others.
The most common grade 3/4 adverse events were febrile neutropenia (43% with quizartinib vs. 41% with placebo), neutropenia (18% vs. 9%), hypokalemia (19% vs. 16%), and pneumonia (11% both). Adverse events were fatal in 11.3% of patients receiving quizartinib versus 9.7% of patients on placebo, mostly caused by infections.
In 2019, the FDA rejected quizartinib for FLT3-ITD mutated relapsed/refractory AML monotherapy in adults, after most of its oncology advisers thought the risk of treatment outweighed the benefits in an earlier trial.
A version of this article first appeared on Medscape.com.
On July 20 the FDA also approved the LeukoStrat CDx FLT3 Mutation Assay to determine whether patients have this mutation.
The agency granted quizartinib a first-line indication for use in combination with standard chemotherapy – cytarabine and anthracycline induction followed by cytarabine consolidation – and as maintenance monotherapy afterwards, in adults whose tumors express FLT3-ITD.
The FLT3 protein is a tyrosine kinase receptor found on hematopoietic stem cells. Wild-type FLT3 promotes cell survival, growth, and differentiation, but ITD (internal tandem duplication)-mutated FLT3, which quizartinib targets, is associated with a higher relapse risk and shorter survival. About a quarter of AML patients carry the mutation.
Approval was based on the phase 3 QuANTUM-First trial in over 500 patients with the mutation. Median overall survival among patients on standard chemotherapy randomly assigned to quizartinib was 31.9 months versus 15.1 months in patients randomly assigned to placebo, a 22.4% reduction in the risk of death (P = .0324).
Quizartinib is not indicated as maintenance monotherapy after allogeneic hematopoietic stem cell transplantation.
In a company press release, the drug’s manufacturer Daiichi Sankyo said quizartinib will be available in the United States soon.
Company executive Ken Takeshita, MD, called the approval “an important milestone, as patients with the FLT3-ITD subtype of AML can now be treated with the first-ever FLT3 inhibitor approved across the three phases of treatment these patients typically receive.”
The FDA’s original decision date was April 24, but the agency pushed it back 3 months to review updates Daiichi Sankyo made to quizartinib’s Risk Evaluation and Mitigation Strategies (REMS) program in response to an agency request.
Quizartinib carries a boxed warning of QT prolongation, torsades de pointes, and cardiac arrest. Because of these risks, it’s only available through a new program, dubbed “Vanflyta REMS.”
In the trial, the most common adverse with quizartinib included lymphopenia (60%), hypokalemia (59%), hypoalbuminemia (53%), hypophosphatemia (52%), alkaline phosphatase increased (51%), hypomagnesemia (44%), febrile neutropenia (44%), diarrhea (42%), mucositis (38%), nausea (34%), and hypocalcemia (33%), among others.
The most common grade 3/4 adverse events were febrile neutropenia (43% with quizartinib vs. 41% with placebo), neutropenia (18% vs. 9%), hypokalemia (19% vs. 16%), and pneumonia (11% both). Adverse events were fatal in 11.3% of patients receiving quizartinib versus 9.7% of patients on placebo, mostly caused by infections.
In 2019, the FDA rejected quizartinib for FLT3-ITD mutated relapsed/refractory AML monotherapy in adults, after most of its oncology advisers thought the risk of treatment outweighed the benefits in an earlier trial.
A version of this article first appeared on Medscape.com.
On July 20 the FDA also approved the LeukoStrat CDx FLT3 Mutation Assay to determine whether patients have this mutation.
The agency granted quizartinib a first-line indication for use in combination with standard chemotherapy – cytarabine and anthracycline induction followed by cytarabine consolidation – and as maintenance monotherapy afterwards, in adults whose tumors express FLT3-ITD.
The FLT3 protein is a tyrosine kinase receptor found on hematopoietic stem cells. Wild-type FLT3 promotes cell survival, growth, and differentiation, but ITD (internal tandem duplication)-mutated FLT3, which quizartinib targets, is associated with a higher relapse risk and shorter survival. About a quarter of AML patients carry the mutation.
Approval was based on the phase 3 QuANTUM-First trial in over 500 patients with the mutation. Median overall survival among patients on standard chemotherapy randomly assigned to quizartinib was 31.9 months versus 15.1 months in patients randomly assigned to placebo, a 22.4% reduction in the risk of death (P = .0324).
Quizartinib is not indicated as maintenance monotherapy after allogeneic hematopoietic stem cell transplantation.
In a company press release, the drug’s manufacturer Daiichi Sankyo said quizartinib will be available in the United States soon.
Company executive Ken Takeshita, MD, called the approval “an important milestone, as patients with the FLT3-ITD subtype of AML can now be treated with the first-ever FLT3 inhibitor approved across the three phases of treatment these patients typically receive.”
The FDA’s original decision date was April 24, but the agency pushed it back 3 months to review updates Daiichi Sankyo made to quizartinib’s Risk Evaluation and Mitigation Strategies (REMS) program in response to an agency request.
Quizartinib carries a boxed warning of QT prolongation, torsades de pointes, and cardiac arrest. Because of these risks, it’s only available through a new program, dubbed “Vanflyta REMS.”
In the trial, the most common adverse with quizartinib included lymphopenia (60%), hypokalemia (59%), hypoalbuminemia (53%), hypophosphatemia (52%), alkaline phosphatase increased (51%), hypomagnesemia (44%), febrile neutropenia (44%), diarrhea (42%), mucositis (38%), nausea (34%), and hypocalcemia (33%), among others.
The most common grade 3/4 adverse events were febrile neutropenia (43% with quizartinib vs. 41% with placebo), neutropenia (18% vs. 9%), hypokalemia (19% vs. 16%), and pneumonia (11% both). Adverse events were fatal in 11.3% of patients receiving quizartinib versus 9.7% of patients on placebo, mostly caused by infections.
In 2019, the FDA rejected quizartinib for FLT3-ITD mutated relapsed/refractory AML monotherapy in adults, after most of its oncology advisers thought the risk of treatment outweighed the benefits in an earlier trial.
A version of this article first appeared on Medscape.com.
An Atypical Discussion of the Link Between Metabolic Syndrome and Type 2 Diabetes—and the Use of Precision Medicine to Treat the Whole Patient
Metabolic syndrome, type 2 diabetes mellitus (T2DM), and the “diabetes syndrome,” are interrelated, serious health conditions that share common risk factors and mechanisms. While they are each distinct conditions, a significant association exists between them, with metabolic syndrome often being considered a precursor to the development of typical T2DM.
Metabolic syndrome is a cluster of individual metabolic abnormalities that includes a combination of risk factors such as abdominal obesity, high blood pressure, elevated insulin levels, high triglyceride levels, and low levels of high-density lipoprotein (HDL) cholesterol related to genes and epigenetic changes associated with insulin resistance. These risk factors increase the likelihood of developing cardiovascular diseases, such as heart disease and stroke, and, when combined with significant damage to β -cell function and the influence of concordant environmental precipitants, result in hyperglycemia/overt diabetes—classically defined as T2DM.
It is estimated that there will be a staggering 3.1 billion people living with T2DM by 2050, according to a recent article in The Lancet. This devastating number will place a heavy burden on the health care system.
However, this typical pathophysiologic definition of T2DM is imprecise. Twenty percent of patients with T2DM have islet-cell antibodies that are typical of the immune destruction of β-cells in patients with type 1 diabetes mellitus (T1DM). Furthermore, approximately 40% of patients with T1DM have insulin resistance.
Thus, to better understand and distinguish the disease processes unique to each individual, we have defined a new beta cell classification for all forms of diabetes mellitus (DM). In this classification, there are 4 common pathophysiologic causes of all DM (including classic T2DM), with resultant damage to the β-cells (ie, genetic and epigenetic changes, inflammation, an abnormal environment, and insulin resistance), which results in 11 mechanisms of hyperglycemia, represented as “the egregious eleven” in Figure 1.
Additionally, Figure 2 illustrates the association between overlapping genes/epigenetic changes responsible for DM and the increased susceptibility to developing various microvascular complications commonly observed in all forms of DM, including classic T2DM. These complications, now recognized as components of the diabetes syndrome, encompass a range of conditions with shared interrelated pathophysiologic mechanisms, such as arteriosclerotic vascular disease (ASVD), dementia, some cancers, nonalcoholic fatty liver disease or nonalcoholic steatohepatitis (NAFLD/NASH), or psoriasis.
The likelihood of developing a specific type of DM, with classic complications or associated conditions, is contingent on an individual’s genes, epigenetic factors, inflammation, insulin resistance, and environmental exposures over time. It has now been postulated that these factors can be identified in a particular individual by a set of genomics, metabolomics, proteomics, and markers of these processes.
This more precise approach has the added benefit of giving rise to a more accurate individualization of therapy—precision medicine.
Precision medicine is an approach to healthcare that considers an individual's specific characteristics, such as genetic makeup, lifestyle, and environmental factors, to tailor medical treatments and interventions. In the context of this discussion on T2DM, precision medicine’s goal is to provide targeted therapies and interventions based on an individual's unique -omic profile to improve treatment outcomes and minimize side effects. An additional benefit of precision medicine use in diabetes syndrome is giving the diabetes specialist the opportunity to treat the whole patient, looking for complications and associated conditions earlier via defining the presence or absence of various markers of their individual pathophysiology. Additionally, we have come to recognize that many of the medications for treating T2DM (eg, glucagon-like peptide 1 receptor agonists [GLP-1 RA], dipeptidyl peptidase 4 inhibitors [DPP-4 inhibitors], sodium-glucose cotransporter-2 inhibitors [SGLT-2 inhibitors], metformin, Cycloset [bromocriptine mesylate]) can offer other benefits for the patient—treating not only multiple mechanisms of hyperglycemia (the egregious eleven: use the fewest number of agents in combination to treat the most number of mechanisms of hyperglycemia) but also recognize that they can prevent and treat the complications and associated conditions of the diabetes syndrome: cardiovascular, renal, liver, some cancers, psoriasis, and dementia.
The classic link between metabolic syndrome and T2DM is important to consider when applying precision medicine approaches to the management of T2DM. Here are some examples of how precision medicine is being applied in the management of T2DM:
Genetic testing: Genetic testing can help identify specific genetic variants or mutations that may influence an individual's risk of developing T2DM or their response to certain medications. By understanding a person's genetic predisposition, clinicians can make more informed decisions about treatment options and develop personalized strategies for their patients.
Pharmacogenomics: Certain genetic variations can impact how a person metabolizes and responds to specific diabetes medications. By analyzing an individual's genetic profile, medications that are more likely to be effective and have fewer adverse effects for that patient may be selected.
Continuous glucose monitoring (CGM): CGM devices provide real-time information about an individual’s blood glucose levels, allowing for more precise management of diabetes. By continuously monitoring glucose levels, patterns can be identified, allowing for adjustments to medication dosages, dietary recommendations, and lifestyle modifications on an individualized basis.
Lifestyle interventions: Precision medicine also recognizes that lifestyle factors play a crucial role in the development and management of T2DM. Lifestyle interventions, such as diet and exercise plans, based on an individual's preferences, metabolic profile, and response to different interventions can be personalized (ie, some individuals may benefit more from a low-carbohydrate diet, while others may respond better to a Mediterranean-style diet).
Predictive modeling and risk stratification: Precision medicine leverages data analytics and predictive modeling to assess an individual's risk of developing complications associated with T2DM. By analyzing various factors such as medical history, genetics, lifestyle, and biomarkers, individuals who are at a higher risk of developing complications can be identified, and their treatment plans can be tailored accordingly. Precision medicine enables early identification of individuals who are at a higher risk of developing T2DM based on their metabolic syndrome status.
In summary, precision medicine for T2DM considers the link between metabolic syndrome and diabetes syndrome to develop personalized approaches for prevention, early intervention, and treatment. By understanding an individual's metabolic and genetic profile, targeted strategies to optimize management and improve outcomes for patients with metabolic syndrome and those at risk of developing diabetes can be implemented.
It is important to note that while precision medicine holds promise in improving diabetes management, it is still an evolving field, and its widespread implementation is not yet fully realized. Collaboration between clinicians, researchers, and technological advancements will continue to drive the progress of precision medicine in T2DM management.
Metabolic syndrome, type 2 diabetes mellitus (T2DM), and the “diabetes syndrome,” are interrelated, serious health conditions that share common risk factors and mechanisms. While they are each distinct conditions, a significant association exists between them, with metabolic syndrome often being considered a precursor to the development of typical T2DM.
Metabolic syndrome is a cluster of individual metabolic abnormalities that includes a combination of risk factors such as abdominal obesity, high blood pressure, elevated insulin levels, high triglyceride levels, and low levels of high-density lipoprotein (HDL) cholesterol related to genes and epigenetic changes associated with insulin resistance. These risk factors increase the likelihood of developing cardiovascular diseases, such as heart disease and stroke, and, when combined with significant damage to β -cell function and the influence of concordant environmental precipitants, result in hyperglycemia/overt diabetes—classically defined as T2DM.
It is estimated that there will be a staggering 3.1 billion people living with T2DM by 2050, according to a recent article in The Lancet. This devastating number will place a heavy burden on the health care system.
However, this typical pathophysiologic definition of T2DM is imprecise. Twenty percent of patients with T2DM have islet-cell antibodies that are typical of the immune destruction of β-cells in patients with type 1 diabetes mellitus (T1DM). Furthermore, approximately 40% of patients with T1DM have insulin resistance.
Thus, to better understand and distinguish the disease processes unique to each individual, we have defined a new beta cell classification for all forms of diabetes mellitus (DM). In this classification, there are 4 common pathophysiologic causes of all DM (including classic T2DM), with resultant damage to the β-cells (ie, genetic and epigenetic changes, inflammation, an abnormal environment, and insulin resistance), which results in 11 mechanisms of hyperglycemia, represented as “the egregious eleven” in Figure 1.
Additionally, Figure 2 illustrates the association between overlapping genes/epigenetic changes responsible for DM and the increased susceptibility to developing various microvascular complications commonly observed in all forms of DM, including classic T2DM. These complications, now recognized as components of the diabetes syndrome, encompass a range of conditions with shared interrelated pathophysiologic mechanisms, such as arteriosclerotic vascular disease (ASVD), dementia, some cancers, nonalcoholic fatty liver disease or nonalcoholic steatohepatitis (NAFLD/NASH), or psoriasis.
The likelihood of developing a specific type of DM, with classic complications or associated conditions, is contingent on an individual’s genes, epigenetic factors, inflammation, insulin resistance, and environmental exposures over time. It has now been postulated that these factors can be identified in a particular individual by a set of genomics, metabolomics, proteomics, and markers of these processes.
This more precise approach has the added benefit of giving rise to a more accurate individualization of therapy—precision medicine.
Precision medicine is an approach to healthcare that considers an individual's specific characteristics, such as genetic makeup, lifestyle, and environmental factors, to tailor medical treatments and interventions. In the context of this discussion on T2DM, precision medicine’s goal is to provide targeted therapies and interventions based on an individual's unique -omic profile to improve treatment outcomes and minimize side effects. An additional benefit of precision medicine use in diabetes syndrome is giving the diabetes specialist the opportunity to treat the whole patient, looking for complications and associated conditions earlier via defining the presence or absence of various markers of their individual pathophysiology. Additionally, we have come to recognize that many of the medications for treating T2DM (eg, glucagon-like peptide 1 receptor agonists [GLP-1 RA], dipeptidyl peptidase 4 inhibitors [DPP-4 inhibitors], sodium-glucose cotransporter-2 inhibitors [SGLT-2 inhibitors], metformin, Cycloset [bromocriptine mesylate]) can offer other benefits for the patient—treating not only multiple mechanisms of hyperglycemia (the egregious eleven: use the fewest number of agents in combination to treat the most number of mechanisms of hyperglycemia) but also recognize that they can prevent and treat the complications and associated conditions of the diabetes syndrome: cardiovascular, renal, liver, some cancers, psoriasis, and dementia.
The classic link between metabolic syndrome and T2DM is important to consider when applying precision medicine approaches to the management of T2DM. Here are some examples of how precision medicine is being applied in the management of T2DM:
Genetic testing: Genetic testing can help identify specific genetic variants or mutations that may influence an individual's risk of developing T2DM or their response to certain medications. By understanding a person's genetic predisposition, clinicians can make more informed decisions about treatment options and develop personalized strategies for their patients.
Pharmacogenomics: Certain genetic variations can impact how a person metabolizes and responds to specific diabetes medications. By analyzing an individual's genetic profile, medications that are more likely to be effective and have fewer adverse effects for that patient may be selected.
Continuous glucose monitoring (CGM): CGM devices provide real-time information about an individual’s blood glucose levels, allowing for more precise management of diabetes. By continuously monitoring glucose levels, patterns can be identified, allowing for adjustments to medication dosages, dietary recommendations, and lifestyle modifications on an individualized basis.
Lifestyle interventions: Precision medicine also recognizes that lifestyle factors play a crucial role in the development and management of T2DM. Lifestyle interventions, such as diet and exercise plans, based on an individual's preferences, metabolic profile, and response to different interventions can be personalized (ie, some individuals may benefit more from a low-carbohydrate diet, while others may respond better to a Mediterranean-style diet).
Predictive modeling and risk stratification: Precision medicine leverages data analytics and predictive modeling to assess an individual's risk of developing complications associated with T2DM. By analyzing various factors such as medical history, genetics, lifestyle, and biomarkers, individuals who are at a higher risk of developing complications can be identified, and their treatment plans can be tailored accordingly. Precision medicine enables early identification of individuals who are at a higher risk of developing T2DM based on their metabolic syndrome status.
In summary, precision medicine for T2DM considers the link between metabolic syndrome and diabetes syndrome to develop personalized approaches for prevention, early intervention, and treatment. By understanding an individual's metabolic and genetic profile, targeted strategies to optimize management and improve outcomes for patients with metabolic syndrome and those at risk of developing diabetes can be implemented.
It is important to note that while precision medicine holds promise in improving diabetes management, it is still an evolving field, and its widespread implementation is not yet fully realized. Collaboration between clinicians, researchers, and technological advancements will continue to drive the progress of precision medicine in T2DM management.
Metabolic syndrome, type 2 diabetes mellitus (T2DM), and the “diabetes syndrome,” are interrelated, serious health conditions that share common risk factors and mechanisms. While they are each distinct conditions, a significant association exists between them, with metabolic syndrome often being considered a precursor to the development of typical T2DM.
Metabolic syndrome is a cluster of individual metabolic abnormalities that includes a combination of risk factors such as abdominal obesity, high blood pressure, elevated insulin levels, high triglyceride levels, and low levels of high-density lipoprotein (HDL) cholesterol related to genes and epigenetic changes associated with insulin resistance. These risk factors increase the likelihood of developing cardiovascular diseases, such as heart disease and stroke, and, when combined with significant damage to β -cell function and the influence of concordant environmental precipitants, result in hyperglycemia/overt diabetes—classically defined as T2DM.
It is estimated that there will be a staggering 3.1 billion people living with T2DM by 2050, according to a recent article in The Lancet. This devastating number will place a heavy burden on the health care system.
However, this typical pathophysiologic definition of T2DM is imprecise. Twenty percent of patients with T2DM have islet-cell antibodies that are typical of the immune destruction of β-cells in patients with type 1 diabetes mellitus (T1DM). Furthermore, approximately 40% of patients with T1DM have insulin resistance.
Thus, to better understand and distinguish the disease processes unique to each individual, we have defined a new beta cell classification for all forms of diabetes mellitus (DM). In this classification, there are 4 common pathophysiologic causes of all DM (including classic T2DM), with resultant damage to the β-cells (ie, genetic and epigenetic changes, inflammation, an abnormal environment, and insulin resistance), which results in 11 mechanisms of hyperglycemia, represented as “the egregious eleven” in Figure 1.
Additionally, Figure 2 illustrates the association between overlapping genes/epigenetic changes responsible for DM and the increased susceptibility to developing various microvascular complications commonly observed in all forms of DM, including classic T2DM. These complications, now recognized as components of the diabetes syndrome, encompass a range of conditions with shared interrelated pathophysiologic mechanisms, such as arteriosclerotic vascular disease (ASVD), dementia, some cancers, nonalcoholic fatty liver disease or nonalcoholic steatohepatitis (NAFLD/NASH), or psoriasis.
The likelihood of developing a specific type of DM, with classic complications or associated conditions, is contingent on an individual’s genes, epigenetic factors, inflammation, insulin resistance, and environmental exposures over time. It has now been postulated that these factors can be identified in a particular individual by a set of genomics, metabolomics, proteomics, and markers of these processes.
This more precise approach has the added benefit of giving rise to a more accurate individualization of therapy—precision medicine.
Precision medicine is an approach to healthcare that considers an individual's specific characteristics, such as genetic makeup, lifestyle, and environmental factors, to tailor medical treatments and interventions. In the context of this discussion on T2DM, precision medicine’s goal is to provide targeted therapies and interventions based on an individual's unique -omic profile to improve treatment outcomes and minimize side effects. An additional benefit of precision medicine use in diabetes syndrome is giving the diabetes specialist the opportunity to treat the whole patient, looking for complications and associated conditions earlier via defining the presence or absence of various markers of their individual pathophysiology. Additionally, we have come to recognize that many of the medications for treating T2DM (eg, glucagon-like peptide 1 receptor agonists [GLP-1 RA], dipeptidyl peptidase 4 inhibitors [DPP-4 inhibitors], sodium-glucose cotransporter-2 inhibitors [SGLT-2 inhibitors], metformin, Cycloset [bromocriptine mesylate]) can offer other benefits for the patient—treating not only multiple mechanisms of hyperglycemia (the egregious eleven: use the fewest number of agents in combination to treat the most number of mechanisms of hyperglycemia) but also recognize that they can prevent and treat the complications and associated conditions of the diabetes syndrome: cardiovascular, renal, liver, some cancers, psoriasis, and dementia.
The classic link between metabolic syndrome and T2DM is important to consider when applying precision medicine approaches to the management of T2DM. Here are some examples of how precision medicine is being applied in the management of T2DM:
Genetic testing: Genetic testing can help identify specific genetic variants or mutations that may influence an individual's risk of developing T2DM or their response to certain medications. By understanding a person's genetic predisposition, clinicians can make more informed decisions about treatment options and develop personalized strategies for their patients.
Pharmacogenomics: Certain genetic variations can impact how a person metabolizes and responds to specific diabetes medications. By analyzing an individual's genetic profile, medications that are more likely to be effective and have fewer adverse effects for that patient may be selected.
Continuous glucose monitoring (CGM): CGM devices provide real-time information about an individual’s blood glucose levels, allowing for more precise management of diabetes. By continuously monitoring glucose levels, patterns can be identified, allowing for adjustments to medication dosages, dietary recommendations, and lifestyle modifications on an individualized basis.
Lifestyle interventions: Precision medicine also recognizes that lifestyle factors play a crucial role in the development and management of T2DM. Lifestyle interventions, such as diet and exercise plans, based on an individual's preferences, metabolic profile, and response to different interventions can be personalized (ie, some individuals may benefit more from a low-carbohydrate diet, while others may respond better to a Mediterranean-style diet).
Predictive modeling and risk stratification: Precision medicine leverages data analytics and predictive modeling to assess an individual's risk of developing complications associated with T2DM. By analyzing various factors such as medical history, genetics, lifestyle, and biomarkers, individuals who are at a higher risk of developing complications can be identified, and their treatment plans can be tailored accordingly. Precision medicine enables early identification of individuals who are at a higher risk of developing T2DM based on their metabolic syndrome status.
In summary, precision medicine for T2DM considers the link between metabolic syndrome and diabetes syndrome to develop personalized approaches for prevention, early intervention, and treatment. By understanding an individual's metabolic and genetic profile, targeted strategies to optimize management and improve outcomes for patients with metabolic syndrome and those at risk of developing diabetes can be implemented.
It is important to note that while precision medicine holds promise in improving diabetes management, it is still an evolving field, and its widespread implementation is not yet fully realized. Collaboration between clinicians, researchers, and technological advancements will continue to drive the progress of precision medicine in T2DM management.
Most Americans in favor of regulated therapeutic psychedelics
It is a surprisingly large percentage, said officials at the University of California, Berkeley, Center for the Science of Psychedelics, which conducted the online survey of 1,500 registered voters in early June.
“That is a stunning number,” said Michael Pollan, cofounder of the center, and author of “How to Change Your Mind,” a book that explored potential uses of psychedelics.
In a briefing with reporters, Mr. Pollan said that he believes the large support base, in part, reflects campaigns that have “been successful by highlighting the effectiveness of psychedelics as therapy for mental illness.”
However, the poll also showed that 61% of voters said that they do not perceive psychedelics as “good for society,” and 69% do not perceive them as “something for people like me.”
These negative sentiments “suggest a fragile kind of support – the kind of support where you’re only hearing one side of the story,” said Mr. Pollan.
Still, poll respondents supported other potential policy changes, including 56% in support of the U.S. Food and Drug Administration vetting and approving psychedelics so they could be available by prescription.
50% have tried psychedelics
Almost 80% said that it should be easier for researchers to study psychedelics, and just under one-half said that they backed removing criminal penalties for personal use and possession.
The poll results also show that almost half of respondents had heard about psychedelics recently, with 48% saying they had heard about the drugs’ use in treating mental illness.
Respondents who were most familiar with and positive about psychedelics tended to be White, male, aged 30-50 years, liberal, highly educated, living in a Western state, and have little to no religious or spiritual practice.
Overall, 52% of survey respondents said that they or someone close to them had used a psychedelic, with almost half of that use coming in the past 5 years. Some 40% said that the use had been more than a decade ago.
Almost three-quarters of psychedelic use was reported as recreational, but the second-biggest category was therapeutic use at 39%. About one-third of respondents said that they or someone close to them had microdosed.
Conservative voters had lower levels of awareness and first-degree connection use as well as the least amount of support for regulated therapeutic use, with only 45% saying they would back such a policy, compared with 80% of liberal voters and 66% of moderate voters.
Black individuals were the least likely to be familiar with psychedelics: Just 29% said that they had heard a little or a lot about the drugs, compared with 39% of Latinx individuals and 51% of White individuals. And just one-quarter reported first-degree use, compared with half of Latinx individuals and 56% of White individuals.
Who should be eligible?
When asked who should be eligible for treatment with psychedelics, 80% said that they were comfortable with its use for those with terminal illnesses. More than two-thirds expressed comfort with the drugs being used to help veterans and people with treatment-resistant depression and anxiety.
Less than one-half of respondents said that psychedelics should be available to everyone older than 21 years. And voters seemed to be less inclined to say psychedelics should be used to treat people with addiction, with just 45% indicating that they were very or somewhat comfortable with that use.
Mr. Pollan said that reflects perhaps some lack of knowledge or education.
“The story about addiction and psychedelics hasn’t gotten out,” he said. “I kind of get that intuitively the idea of using a drug to treat a drug doesn’t sound right to a lot of people. But in fact, there’s good evidence it works,” Mr. Pollan said.
Respondents said that doctors, nurses, and scientists were the most trusted source of information about psychedelics, whereas the FDA received lower confidence. Law enforcement was least trusted by liberals and most trusted by conservatives.
Mr. Pollan noted the reversal in attitudes, with Americans mostly now looking to the scientific and medical establishment for guidance on psychedelics.
“We went from a counterculture drug to something that is being taken seriously by scientists as a potential therapy,” he said.
The poll’s margin of error was ± 2.5%.
A version of this article first appeared on Medscape.com.
It is a surprisingly large percentage, said officials at the University of California, Berkeley, Center for the Science of Psychedelics, which conducted the online survey of 1,500 registered voters in early June.
“That is a stunning number,” said Michael Pollan, cofounder of the center, and author of “How to Change Your Mind,” a book that explored potential uses of psychedelics.
In a briefing with reporters, Mr. Pollan said that he believes the large support base, in part, reflects campaigns that have “been successful by highlighting the effectiveness of psychedelics as therapy for mental illness.”
However, the poll also showed that 61% of voters said that they do not perceive psychedelics as “good for society,” and 69% do not perceive them as “something for people like me.”
These negative sentiments “suggest a fragile kind of support – the kind of support where you’re only hearing one side of the story,” said Mr. Pollan.
Still, poll respondents supported other potential policy changes, including 56% in support of the U.S. Food and Drug Administration vetting and approving psychedelics so they could be available by prescription.
50% have tried psychedelics
Almost 80% said that it should be easier for researchers to study psychedelics, and just under one-half said that they backed removing criminal penalties for personal use and possession.
The poll results also show that almost half of respondents had heard about psychedelics recently, with 48% saying they had heard about the drugs’ use in treating mental illness.
Respondents who were most familiar with and positive about psychedelics tended to be White, male, aged 30-50 years, liberal, highly educated, living in a Western state, and have little to no religious or spiritual practice.
Overall, 52% of survey respondents said that they or someone close to them had used a psychedelic, with almost half of that use coming in the past 5 years. Some 40% said that the use had been more than a decade ago.
Almost three-quarters of psychedelic use was reported as recreational, but the second-biggest category was therapeutic use at 39%. About one-third of respondents said that they or someone close to them had microdosed.
Conservative voters had lower levels of awareness and first-degree connection use as well as the least amount of support for regulated therapeutic use, with only 45% saying they would back such a policy, compared with 80% of liberal voters and 66% of moderate voters.
Black individuals were the least likely to be familiar with psychedelics: Just 29% said that they had heard a little or a lot about the drugs, compared with 39% of Latinx individuals and 51% of White individuals. And just one-quarter reported first-degree use, compared with half of Latinx individuals and 56% of White individuals.
Who should be eligible?
When asked who should be eligible for treatment with psychedelics, 80% said that they were comfortable with its use for those with terminal illnesses. More than two-thirds expressed comfort with the drugs being used to help veterans and people with treatment-resistant depression and anxiety.
Less than one-half of respondents said that psychedelics should be available to everyone older than 21 years. And voters seemed to be less inclined to say psychedelics should be used to treat people with addiction, with just 45% indicating that they were very or somewhat comfortable with that use.
Mr. Pollan said that reflects perhaps some lack of knowledge or education.
“The story about addiction and psychedelics hasn’t gotten out,” he said. “I kind of get that intuitively the idea of using a drug to treat a drug doesn’t sound right to a lot of people. But in fact, there’s good evidence it works,” Mr. Pollan said.
Respondents said that doctors, nurses, and scientists were the most trusted source of information about psychedelics, whereas the FDA received lower confidence. Law enforcement was least trusted by liberals and most trusted by conservatives.
Mr. Pollan noted the reversal in attitudes, with Americans mostly now looking to the scientific and medical establishment for guidance on psychedelics.
“We went from a counterculture drug to something that is being taken seriously by scientists as a potential therapy,” he said.
The poll’s margin of error was ± 2.5%.
A version of this article first appeared on Medscape.com.
It is a surprisingly large percentage, said officials at the University of California, Berkeley, Center for the Science of Psychedelics, which conducted the online survey of 1,500 registered voters in early June.
“That is a stunning number,” said Michael Pollan, cofounder of the center, and author of “How to Change Your Mind,” a book that explored potential uses of psychedelics.
In a briefing with reporters, Mr. Pollan said that he believes the large support base, in part, reflects campaigns that have “been successful by highlighting the effectiveness of psychedelics as therapy for mental illness.”
However, the poll also showed that 61% of voters said that they do not perceive psychedelics as “good for society,” and 69% do not perceive them as “something for people like me.”
These negative sentiments “suggest a fragile kind of support – the kind of support where you’re only hearing one side of the story,” said Mr. Pollan.
Still, poll respondents supported other potential policy changes, including 56% in support of the U.S. Food and Drug Administration vetting and approving psychedelics so they could be available by prescription.
50% have tried psychedelics
Almost 80% said that it should be easier for researchers to study psychedelics, and just under one-half said that they backed removing criminal penalties for personal use and possession.
The poll results also show that almost half of respondents had heard about psychedelics recently, with 48% saying they had heard about the drugs’ use in treating mental illness.
Respondents who were most familiar with and positive about psychedelics tended to be White, male, aged 30-50 years, liberal, highly educated, living in a Western state, and have little to no religious or spiritual practice.
Overall, 52% of survey respondents said that they or someone close to them had used a psychedelic, with almost half of that use coming in the past 5 years. Some 40% said that the use had been more than a decade ago.
Almost three-quarters of psychedelic use was reported as recreational, but the second-biggest category was therapeutic use at 39%. About one-third of respondents said that they or someone close to them had microdosed.
Conservative voters had lower levels of awareness and first-degree connection use as well as the least amount of support for regulated therapeutic use, with only 45% saying they would back such a policy, compared with 80% of liberal voters and 66% of moderate voters.
Black individuals were the least likely to be familiar with psychedelics: Just 29% said that they had heard a little or a lot about the drugs, compared with 39% of Latinx individuals and 51% of White individuals. And just one-quarter reported first-degree use, compared with half of Latinx individuals and 56% of White individuals.
Who should be eligible?
When asked who should be eligible for treatment with psychedelics, 80% said that they were comfortable with its use for those with terminal illnesses. More than two-thirds expressed comfort with the drugs being used to help veterans and people with treatment-resistant depression and anxiety.
Less than one-half of respondents said that psychedelics should be available to everyone older than 21 years. And voters seemed to be less inclined to say psychedelics should be used to treat people with addiction, with just 45% indicating that they were very or somewhat comfortable with that use.
Mr. Pollan said that reflects perhaps some lack of knowledge or education.
“The story about addiction and psychedelics hasn’t gotten out,” he said. “I kind of get that intuitively the idea of using a drug to treat a drug doesn’t sound right to a lot of people. But in fact, there’s good evidence it works,” Mr. Pollan said.
Respondents said that doctors, nurses, and scientists were the most trusted source of information about psychedelics, whereas the FDA received lower confidence. Law enforcement was least trusted by liberals and most trusted by conservatives.
Mr. Pollan noted the reversal in attitudes, with Americans mostly now looking to the scientific and medical establishment for guidance on psychedelics.
“We went from a counterculture drug to something that is being taken seriously by scientists as a potential therapy,” he said.
The poll’s margin of error was ± 2.5%.
A version of this article first appeared on Medscape.com.
High-intensity interval training before major surgery may boost postoperative outcomes
TOPLINE:
It cuts the risk of postoperative complications and may shorten hospital length of stay and improve postoperative quality of life.
METHODOLOGY:
Evidence suggests CRF – which improves physical and cognitive function and is associated with a reduction in cardiovascular risk – can be enhanced before major surgeries, but reported postoperative outcomes in previous reviews have been inconsistent.
In the study, HIIT involved repeated aerobic high-intensity exercise intervals at about 80% of maximum heart rate, followed by active recovery.
The meta-analysis included 12 studies with 832 patients (mean age, 67) that compared preoperative HIIT – supervised at hospitals, gyms, or community or physical therapy centers, or unsupervised at home – with standard care for patients slated for major surgery, including liver, lung, colorectal, urologic, and mixed major abdominal operations.
The primary outcome was change in CRF by peak VO2 or 6-minute walk test; other endpoints included change in endurance time and postoperative outcomes.
TAKEAWAY:
Preoperative HIIT (median total, 160 minutes; range, 80-240 minutes; intense exercise during 6-40 sessions) was associated with an increase in peak oxygen consumption (VO2 peak) by 2.59 mL/kg/min (95% confidence interval, 1.52-3.65 mL/kg/min; P < .001), compared with standard care, which represents about a 10% increase in CRF.
In eight studies that involved 770 patients, there was moderate evidence that preoperative HIIT cut the odds ratio for postoperative complications by more than half (OR, 0.44; 95% CI, 0.32-0.60; P < .001); there was a similar apparent benefit in an analysis that was limited to patients who were slated for abdominal surgery (OR, 0.45; 95% CI, 0.29-0.68; P < .001).
An analysis that was limited to studies that reported hospital length of stay showed a clinically relevant but nonsignificant 3-day reduction among patients in the HIIT groups.
Most quality of life assessments did not show post-HIIT improvements; some showed a significant benefit 6 weeks after surgery.
IN PRACTICE:
The results suggest preoperative HIIT may improve postoperative outcomes. By extension, it could be cost-effective and “should be included in prehabilitation programs,” the report states.
SOURCE:
The study was carried out by Kari Clifford, PhD, Otago Medical School, University of Otago, Dunedin, New Zealand, and colleagues. It was published online June 30, 2023, in JAMA Network Open.
LIMITATIONS:
Included studies were heterogeneous in methodology; for example, HIIT definitions and protocols varied across almost every study. Data reporting was incomplete, the samples sizes in the studies were limited, and patients could not be blinded to their intervention. The patients could not be stratified on the basis of frailty. There were limited HIIT data from patients who underwent orthopedic surgeries.
DISCLOSURES:
The study received funding from the University of Otago. The authors reported no conflicts.
A version of this article first appeared on Medscape.com.
TOPLINE:
It cuts the risk of postoperative complications and may shorten hospital length of stay and improve postoperative quality of life.
METHODOLOGY:
Evidence suggests CRF – which improves physical and cognitive function and is associated with a reduction in cardiovascular risk – can be enhanced before major surgeries, but reported postoperative outcomes in previous reviews have been inconsistent.
In the study, HIIT involved repeated aerobic high-intensity exercise intervals at about 80% of maximum heart rate, followed by active recovery.
The meta-analysis included 12 studies with 832 patients (mean age, 67) that compared preoperative HIIT – supervised at hospitals, gyms, or community or physical therapy centers, or unsupervised at home – with standard care for patients slated for major surgery, including liver, lung, colorectal, urologic, and mixed major abdominal operations.
The primary outcome was change in CRF by peak VO2 or 6-minute walk test; other endpoints included change in endurance time and postoperative outcomes.
TAKEAWAY:
Preoperative HIIT (median total, 160 minutes; range, 80-240 minutes; intense exercise during 6-40 sessions) was associated with an increase in peak oxygen consumption (VO2 peak) by 2.59 mL/kg/min (95% confidence interval, 1.52-3.65 mL/kg/min; P < .001), compared with standard care, which represents about a 10% increase in CRF.
In eight studies that involved 770 patients, there was moderate evidence that preoperative HIIT cut the odds ratio for postoperative complications by more than half (OR, 0.44; 95% CI, 0.32-0.60; P < .001); there was a similar apparent benefit in an analysis that was limited to patients who were slated for abdominal surgery (OR, 0.45; 95% CI, 0.29-0.68; P < .001).
An analysis that was limited to studies that reported hospital length of stay showed a clinically relevant but nonsignificant 3-day reduction among patients in the HIIT groups.
Most quality of life assessments did not show post-HIIT improvements; some showed a significant benefit 6 weeks after surgery.
IN PRACTICE:
The results suggest preoperative HIIT may improve postoperative outcomes. By extension, it could be cost-effective and “should be included in prehabilitation programs,” the report states.
SOURCE:
The study was carried out by Kari Clifford, PhD, Otago Medical School, University of Otago, Dunedin, New Zealand, and colleagues. It was published online June 30, 2023, in JAMA Network Open.
LIMITATIONS:
Included studies were heterogeneous in methodology; for example, HIIT definitions and protocols varied across almost every study. Data reporting was incomplete, the samples sizes in the studies were limited, and patients could not be blinded to their intervention. The patients could not be stratified on the basis of frailty. There were limited HIIT data from patients who underwent orthopedic surgeries.
DISCLOSURES:
The study received funding from the University of Otago. The authors reported no conflicts.
A version of this article first appeared on Medscape.com.
TOPLINE:
It cuts the risk of postoperative complications and may shorten hospital length of stay and improve postoperative quality of life.
METHODOLOGY:
Evidence suggests CRF – which improves physical and cognitive function and is associated with a reduction in cardiovascular risk – can be enhanced before major surgeries, but reported postoperative outcomes in previous reviews have been inconsistent.
In the study, HIIT involved repeated aerobic high-intensity exercise intervals at about 80% of maximum heart rate, followed by active recovery.
The meta-analysis included 12 studies with 832 patients (mean age, 67) that compared preoperative HIIT – supervised at hospitals, gyms, or community or physical therapy centers, or unsupervised at home – with standard care for patients slated for major surgery, including liver, lung, colorectal, urologic, and mixed major abdominal operations.
The primary outcome was change in CRF by peak VO2 or 6-minute walk test; other endpoints included change in endurance time and postoperative outcomes.
TAKEAWAY:
Preoperative HIIT (median total, 160 minutes; range, 80-240 minutes; intense exercise during 6-40 sessions) was associated with an increase in peak oxygen consumption (VO2 peak) by 2.59 mL/kg/min (95% confidence interval, 1.52-3.65 mL/kg/min; P < .001), compared with standard care, which represents about a 10% increase in CRF.
In eight studies that involved 770 patients, there was moderate evidence that preoperative HIIT cut the odds ratio for postoperative complications by more than half (OR, 0.44; 95% CI, 0.32-0.60; P < .001); there was a similar apparent benefit in an analysis that was limited to patients who were slated for abdominal surgery (OR, 0.45; 95% CI, 0.29-0.68; P < .001).
An analysis that was limited to studies that reported hospital length of stay showed a clinically relevant but nonsignificant 3-day reduction among patients in the HIIT groups.
Most quality of life assessments did not show post-HIIT improvements; some showed a significant benefit 6 weeks after surgery.
IN PRACTICE:
The results suggest preoperative HIIT may improve postoperative outcomes. By extension, it could be cost-effective and “should be included in prehabilitation programs,” the report states.
SOURCE:
The study was carried out by Kari Clifford, PhD, Otago Medical School, University of Otago, Dunedin, New Zealand, and colleagues. It was published online June 30, 2023, in JAMA Network Open.
LIMITATIONS:
Included studies were heterogeneous in methodology; for example, HIIT definitions and protocols varied across almost every study. Data reporting was incomplete, the samples sizes in the studies were limited, and patients could not be blinded to their intervention. The patients could not be stratified on the basis of frailty. There were limited HIIT data from patients who underwent orthopedic surgeries.
DISCLOSURES:
The study received funding from the University of Otago. The authors reported no conflicts.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN