In 2016, as vice president, Joe Biden launched the Cancer Moonshot program just 1 year after his son Beau died from glioblastoma multiforme. His objective, he said, was to “cure” cancer, but to get close to that goal, researchers from two leading National Cancer Institute-designated cancer centers say an infusion of new funding for cancer research is needed to get cancer research just back up to pre-COVID-19 pandemic levels.

There has been a significant decrease in the launch of new clinical trials for cancer and biologic therapies since 2020. “That can affect every aspect of our research operation. It really affected our capacity to continue to move forward at a fast pace. It will require a behemoth effort to get back to pre-COVID times,” said Tanios S. Bekaii-Saab, MD, leader of the gastrointestinal cancer program at Mayo Clinic in Phoenix.

Congress passed the 21st Century Cures Act in 2016 authorizing $1.8 billion for Cancer Moonshot over 7 years. More recently, the program received $194 million from the $6.9 billion National Cancer Institute budget in FY 2022.

Joseph Alvarnas, MD, a hematologist oncologist and vice president of government affairs at City of Hope, Duarte, Calif., sees the Moonshot budget as a potential shortcoming.

“The priorities are well founded and based on what we would think are the most important things to cover, but, if we’re going to achieve these extraordinarily ambitious goals of halving cancer mortality and serving communities more equitably, it’s going to need more funding positioned at making these things real,” he said.

Moonshot is being positioned as an opportunity to double down on efforts started in 2016, but treating cancer is complex and goes well beyond funding new research.

“We know that we have amazing research and progress around innovations that will drive us toward the goal of reducing the death rate from cancer. But we also know that we have tools that aren’t reaching all parts of the country, so we have a great opportunity to make sure that we’re doing all we can to prevent, detect and treat cancer,” Dr. Carnival said.
 

Can cancer be cured?

The Biden administration relaunched Moonshot in 2022 with newly defined goals: Cut the rate of cancer-related deaths in half within 25 years; improve the experience of people with cancer, cancer survivors, and their families; and “end cancer as we know it,” President Biden said in a press conference in February.

Cancer is the second leading cause of death in the United States after heart disease, but it may indeed be possible to cut the total number of cancer-related deaths in half over the next 25 years.

“As a hematologist who’s been involved in both research and clinical care, I think it’s important to realize this is actually doable. Between 1990 and 2020 cancer mortality rates decreased by 31%, and in the last American Cancer Society’s annual report, mortality rates dropped by the largest percentages for 2 consecutive years in a row. The question shifts now from ‘Is this possible? to ‘How do we ensure that it’s possible?’ The spirit of Cancer Moonshot 2.0 is identifying the multiple paths to move this effort forward,” Dr. Alvarnas said.

But without a significant infusion of cash for research, it’s doubtful cancer-related deaths will drop by 50% over the next 25 years.

“There are a lot of big and lofty goals in Cancer Moonshot, and the words ‘ending cancer,’ well those are big words,” Dr. Bekaii-Saab said. “The reality is how do we measure in 25 years the impact of this today? I think it will require significantly more funding over the next few years to achieve the goals set by the Moonshot. Otherwise it will be a 7-year done deal that will accrue a lot of great numbers but won’t make a dent in those goals for the next 25 years. To stop it at some point and not invest more into it, we will probably lose most of the benefit.”

Closing the loop on data sharing

Moonshot has been instrumental in fostering research collaborations by encouraging data sharing among scientists.

“It also brought together a new way for the National Cancer Institute and Department of Energy to drive progress on some of the big data initiatives. The initial Cancer Moonshot infused a sense of urgency and hope into this effort,” said Danielle Carnival, PhD, coordinator of Cancer Moonshot.

Between 2017 and 2022, Cancer Moonshot created more than 70 consortiums or programs, and funded about 240 research projects. Its fundamental goals of improving data sharing and encouraging collaboration are very important, Dr. Bekaii-Saab said.

“Because, historically, what happens with cancer is that researchers compete for resources...and they become very protective of their data. Sharing gets more difficult, collaborations become more onerous, and it becomes counterproductive,” he said.

Dr. Bekaii-Saab highlighted two networks created specifically for data sharing. They include the Human Tumor Atlas for cellular, morphological, and molecular tumor data, and PDXNet, a patient derived xenograft research network.
 

A shift in funding priorities?

Cancer funding has been stagnant for years. When adjusted for growth, it hasn’t had a significant infusion of funding since at least 2003—at least in relative terms, Dr. Bekaii-Saab said. “This affects a lot of the things we do, including NCI-funded clinical trials. It pushes us to work with the private sector, which is not necessarily a detriment, but it doesn’t advance the academic mission at the same level. So, overall, I wouldn’t call it tragic, but I do think we’re falling behind,” he said.

“I think when we do the process for the budget for FY24 and after we’ve had time to really explore the best ideas and build the foundation for some of these new aspects of the Cancer Moonshot, we hope to have something more concrete going toward these efforts,” Dr. Carnival said.

But in addition to funding, Dr. Alvarnas says, it is equally important to address gaps in care. Not all patients have access to existing cancer treatments.

“The great challenge to us in the 2020s is not only about developing new and more effective technologies, but also in doing a better job of getting existing life-saving treatments into the hands of underserved populations. One of the really positive challenges set forth by the Biden administration is the idea that financing care equity is as important, if not more so, than advancing technologies. If there’s been stagnation, it’s because from a government and resourcing point of view, that priority has been ineffectively supported financially.”
 

The pandemic stymies cancer research

The pandemic has had a significant impact on cancer research. As in other fields, it disrupted ongoing research, but it may have also contributed to the loss of employees who resigned in what’s been called the “Great Resignation.” “A lot of employees just decided to change jobs in the middle of the pandemic, which led to a cancer research staffing crisis,” Dr. Bekaii-Saab said.

“We all recognized that turning so much of the attention of the entire biomedical research engine and health system to the COVID-19 pandemic would have an impact across cancer research, screenings and care,” Dr. Carnival said. “There is work to do to get us back to whole, but from a research perspective, we’ve seen a reorientation of the trial networks we were using for COVID-19 research, back to their initial purpose. Some of those are cancer and oncology networks, so we’re excited about that and fully believe that we can catch up.”

But then there’s also the impact the pandemic has had on cancer patients who delayed their care at the primary level. This, Dr. Bekaii-Saab fears, will lead to more patients presenting with more advanced disease in years to come. “One of the biggest problems was that a lot of patients delayed their care at the primary level. My biggest concern is that in the years to come we will see a lot more patients presenting with more advanced cancer.”

In 2016, as vice president, Joe Biden launched the Cancer Moonshot program just 1 year after his son Beau died from glioblastoma multiforme. His objective, he said, was to “cure” cancer, but to get close to that goal, researchers from two leading National Cancer Institute-designated cancer centers say an infusion of new funding for cancer research is needed to get cancer research just back up to pre-COVID-19 pandemic levels.

There has been a significant decrease in the launch of new clinical trials for cancer and biologic therapies since 2020. “That can affect every aspect of our research operation. It really affected our capacity to continue to move forward at a fast pace. It will require a behemoth effort to get back to pre-COVID times,” said Tanios S. Bekaii-Saab, MD, leader of the gastrointestinal cancer program at Mayo Clinic in Phoenix.

Congress passed the 21st Century Cures Act in 2016 authorizing $1.8 billion for Cancer Moonshot over 7 years. More recently, the program received $194 million from the $6.9 billion National Cancer Institute budget in FY 2022.

Joseph Alvarnas, MD, a hematologist oncologist and vice president of government affairs at City of Hope, Duarte, Calif., sees the Moonshot budget as a potential shortcoming.

“The priorities are well founded and based on what we would think are the most important things to cover, but, if we’re going to achieve these extraordinarily ambitious goals of halving cancer mortality and serving communities more equitably, it’s going to need more funding positioned at making these things real,” he said.

Moonshot is being positioned as an opportunity to double down on efforts started in 2016, but treating cancer is complex and goes well beyond funding new research.

“We know that we have amazing research and progress around innovations that will drive us toward the goal of reducing the death rate from cancer. But we also know that we have tools that aren’t reaching all parts of the country, so we have a great opportunity to make sure that we’re doing all we can to prevent, detect and treat cancer,” Dr. Carnival said.
 

Can cancer be cured?

The Biden administration relaunched Moonshot in 2022 with newly defined goals: Cut the rate of cancer-related deaths in half within 25 years; improve the experience of people with cancer, cancer survivors, and their families; and “end cancer as we know it,” President Biden said in a press conference in February.

Cancer is the second leading cause of death in the United States after heart disease, but it may indeed be possible to cut the total number of cancer-related deaths in half over the next 25 years.

“As a hematologist who’s been involved in both research and clinical care, I think it’s important to realize this is actually doable. Between 1990 and 2020 cancer mortality rates decreased by 31%, and in the last American Cancer Society’s annual report, mortality rates dropped by the largest percentages for 2 consecutive years in a row. The question shifts now from ‘Is this possible? to ‘How do we ensure that it’s possible?’ The spirit of Cancer Moonshot 2.0 is identifying the multiple paths to move this effort forward,” Dr. Alvarnas said.

But without a significant infusion of cash for research, it’s doubtful cancer-related deaths will drop by 50% over the next 25 years.

“There are a lot of big and lofty goals in Cancer Moonshot, and the words ‘ending cancer,’ well those are big words,” Dr. Bekaii-Saab said. “The reality is how do we measure in 25 years the impact of this today? I think it will require significantly more funding over the next few years to achieve the goals set by the Moonshot. Otherwise it will be a 7-year done deal that will accrue a lot of great numbers but won’t make a dent in those goals for the next 25 years. To stop it at some point and not invest more into it, we will probably lose most of the benefit.”

Closing the loop on data sharing

Moonshot has been instrumental in fostering research collaborations by encouraging data sharing among scientists.

“It also brought together a new way for the National Cancer Institute and Department of Energy to drive progress on some of the big data initiatives. The initial Cancer Moonshot infused a sense of urgency and hope into this effort,” said Danielle Carnival, PhD, coordinator of Cancer Moonshot.

Between 2017 and 2022, Cancer Moonshot created more than 70 consortiums or programs, and funded about 240 research projects. Its fundamental goals of improving data sharing and encouraging collaboration are very important, Dr. Bekaii-Saab said.

“Because, historically, what happens with cancer is that researchers compete for resources...and they become very protective of their data. Sharing gets more difficult, collaborations become more onerous, and it becomes counterproductive,” he said.

Dr. Bekaii-Saab highlighted two networks created specifically for data sharing. They include the Human Tumor Atlas for cellular, morphological, and molecular tumor data, and PDXNet, a patient derived xenograft research network.
 

A shift in funding priorities?

Cancer funding has been stagnant for years. When adjusted for growth, it hasn’t had a significant infusion of funding since at least 2003—at least in relative terms, Dr. Bekaii-Saab said. “This affects a lot of the things we do, including NCI-funded clinical trials. It pushes us to work with the private sector, which is not necessarily a detriment, but it doesn’t advance the academic mission at the same level. So, overall, I wouldn’t call it tragic, but I do think we’re falling behind,” he said.

“I think when we do the process for the budget for FY24 and after we’ve had time to really explore the best ideas and build the foundation for some of these new aspects of the Cancer Moonshot, we hope to have something more concrete going toward these efforts,” Dr. Carnival said.

But in addition to funding, Dr. Alvarnas says, it is equally important to address gaps in care. Not all patients have access to existing cancer treatments.

“The great challenge to us in the 2020s is not only about developing new and more effective technologies, but also in doing a better job of getting existing life-saving treatments into the hands of underserved populations. One of the really positive challenges set forth by the Biden administration is the idea that financing care equity is as important, if not more so, than advancing technologies. If there’s been stagnation, it’s because from a government and resourcing point of view, that priority has been ineffectively supported financially.”
 

The pandemic stymies cancer research

The pandemic has had a significant impact on cancer research. As in other fields, it disrupted ongoing research, but it may have also contributed to the loss of employees who resigned in what’s been called the “Great Resignation.” “A lot of employees just decided to change jobs in the middle of the pandemic, which led to a cancer research staffing crisis,” Dr. Bekaii-Saab said.

“We all recognized that turning so much of the attention of the entire biomedical research engine and health system to the COVID-19 pandemic would have an impact across cancer research, screenings and care,” Dr. Carnival said. “There is work to do to get us back to whole, but from a research perspective, we’ve seen a reorientation of the trial networks we were using for COVID-19 research, back to their initial purpose. Some of those are cancer and oncology networks, so we’re excited about that and fully believe that we can catch up.”

But then there’s also the impact the pandemic has had on cancer patients who delayed their care at the primary level. This, Dr. Bekaii-Saab fears, will lead to more patients presenting with more advanced disease in years to come. “One of the biggest problems was that a lot of patients delayed their care at the primary level. My biggest concern is that in the years to come we will see a lot more patients presenting with more advanced cancer.”

In 2016, as vice president, Joe Biden launched the Cancer Moonshot program just 1 year after his son Beau died from glioblastoma multiforme. His objective, he said, was to “cure” cancer, but to get close to that goal, researchers from two leading National Cancer Institute-designated cancer centers say an infusion of new funding for cancer research is needed to get cancer research just back up to pre-COVID-19 pandemic levels.

There has been a significant decrease in the launch of new clinical trials for cancer and biologic therapies since 2020. “That can affect every aspect of our research operation. It really affected our capacity to continue to move forward at a fast pace. It will require a behemoth effort to get back to pre-COVID times,” said Tanios S. Bekaii-Saab, MD, leader of the gastrointestinal cancer program at Mayo Clinic in Phoenix.

Congress passed the 21st Century Cures Act in 2016 authorizing $1.8 billion for Cancer Moonshot over 7 years. More recently, the program received $194 million from the $6.9 billion National Cancer Institute budget in FY 2022.

Joseph Alvarnas, MD, a hematologist oncologist and vice president of government affairs at City of Hope, Duarte, Calif., sees the Moonshot budget as a potential shortcoming.

“The priorities are well founded and based on what we would think are the most important things to cover, but, if we’re going to achieve these extraordinarily ambitious goals of halving cancer mortality and serving communities more equitably, it’s going to need more funding positioned at making these things real,” he said.

Moonshot is being positioned as an opportunity to double down on efforts started in 2016, but treating cancer is complex and goes well beyond funding new research.

“We know that we have amazing research and progress around innovations that will drive us toward the goal of reducing the death rate from cancer. But we also know that we have tools that aren’t reaching all parts of the country, so we have a great opportunity to make sure that we’re doing all we can to prevent, detect and treat cancer,” Dr. Carnival said.
 

Can cancer be cured?

The Biden administration relaunched Moonshot in 2022 with newly defined goals: Cut the rate of cancer-related deaths in half within 25 years; improve the experience of people with cancer, cancer survivors, and their families; and “end cancer as we know it,” President Biden said in a press conference in February.

Cancer is the second leading cause of death in the United States after heart disease, but it may indeed be possible to cut the total number of cancer-related deaths in half over the next 25 years.

“As a hematologist who’s been involved in both research and clinical care, I think it’s important to realize this is actually doable. Between 1990 and 2020 cancer mortality rates decreased by 31%, and in the last American Cancer Society’s annual report, mortality rates dropped by the largest percentages for 2 consecutive years in a row. The question shifts now from ‘Is this possible? to ‘How do we ensure that it’s possible?’ The spirit of Cancer Moonshot 2.0 is identifying the multiple paths to move this effort forward,” Dr. Alvarnas said.

But without a significant infusion of cash for research, it’s doubtful cancer-related deaths will drop by 50% over the next 25 years.

“There are a lot of big and lofty goals in Cancer Moonshot, and the words ‘ending cancer,’ well those are big words,” Dr. Bekaii-Saab said. “The reality is how do we measure in 25 years the impact of this today? I think it will require significantly more funding over the next few years to achieve the goals set by the Moonshot. Otherwise it will be a 7-year done deal that will accrue a lot of great numbers but won’t make a dent in those goals for the next 25 years. To stop it at some point and not invest more into it, we will probably lose most of the benefit.”

Closing the loop on data sharing

Moonshot has been instrumental in fostering research collaborations by encouraging data sharing among scientists.

“It also brought together a new way for the National Cancer Institute and Department of Energy to drive progress on some of the big data initiatives. The initial Cancer Moonshot infused a sense of urgency and hope into this effort,” said Danielle Carnival, PhD, coordinator of Cancer Moonshot.

Between 2017 and 2022, Cancer Moonshot created more than 70 consortiums or programs, and funded about 240 research projects. Its fundamental goals of improving data sharing and encouraging collaboration are very important, Dr. Bekaii-Saab said.

“Because, historically, what happens with cancer is that researchers compete for resources...and they become very protective of their data. Sharing gets more difficult, collaborations become more onerous, and it becomes counterproductive,” he said.

Dr. Bekaii-Saab highlighted two networks created specifically for data sharing. They include the Human Tumor Atlas for cellular, morphological, and molecular tumor data, and PDXNet, a patient derived xenograft research network.
 

A shift in funding priorities?

Cancer funding has been stagnant for years. When adjusted for growth, it hasn’t had a significant infusion of funding since at least 2003—at least in relative terms, Dr. Bekaii-Saab said. “This affects a lot of the things we do, including NCI-funded clinical trials. It pushes us to work with the private sector, which is not necessarily a detriment, but it doesn’t advance the academic mission at the same level. So, overall, I wouldn’t call it tragic, but I do think we’re falling behind,” he said.

“I think when we do the process for the budget for FY24 and after we’ve had time to really explore the best ideas and build the foundation for some of these new aspects of the Cancer Moonshot, we hope to have something more concrete going toward these efforts,” Dr. Carnival said.

But in addition to funding, Dr. Alvarnas says, it is equally important to address gaps in care. Not all patients have access to existing cancer treatments.

“The great challenge to us in the 2020s is not only about developing new and more effective technologies, but also in doing a better job of getting existing life-saving treatments into the hands of underserved populations. One of the really positive challenges set forth by the Biden administration is the idea that financing care equity is as important, if not more so, than advancing technologies. If there’s been stagnation, it’s because from a government and resourcing point of view, that priority has been ineffectively supported financially.”
 

The pandemic stymies cancer research

The pandemic has had a significant impact on cancer research. As in other fields, it disrupted ongoing research, but it may have also contributed to the loss of employees who resigned in what’s been called the “Great Resignation.” “A lot of employees just decided to change jobs in the middle of the pandemic, which led to a cancer research staffing crisis,” Dr. Bekaii-Saab said.

“We all recognized that turning so much of the attention of the entire biomedical research engine and health system to the COVID-19 pandemic would have an impact across cancer research, screenings and care,” Dr. Carnival said. “There is work to do to get us back to whole, but from a research perspective, we’ve seen a reorientation of the trial networks we were using for COVID-19 research, back to their initial purpose. Some of those are cancer and oncology networks, so we’re excited about that and fully believe that we can catch up.”

But then there’s also the impact the pandemic has had on cancer patients who delayed their care at the primary level. This, Dr. Bekaii-Saab fears, will lead to more patients presenting with more advanced disease in years to come. “One of the biggest problems was that a lot of patients delayed their care at the primary level. My biggest concern is that in the years to come we will see a lot more patients presenting with more advanced cancer.”

Switching from one biosimilar medication to another is safe and effective, a new systematic review indicates, even though this clinical practice is not governed by current health authority regulations or guidance.

“No reduction in effectiveness or increase in adverse events was detected in biosimilar-to-biosimilar switching studies conducted to date,” the review’s authors noted in their study, published online in BioDrugs.

“The possibility of multiple switches between biosimilars of the same reference biologic is already a reality, and these types of switches are expected to become more common in the future. ... Although it is not covered by current health authority regulations or guidance,” added the authors, led by Hillel P. Cohen, PhD, executive director of scientific affairs at Sandoz, a division of Novartis.

The researchers searched electronic databases through December 2021 and found 23 observational studies that met their search criteria, of which 13 were published in peer-reviewed journals; the remainder appeared in abstract form. The studies totaled 3,657 patients. The researchers did not identify any randomized clinical trials.

“The studies were heterogeneous in size, design, and endpoints, providing data on safety, effectiveness, immunogenicity, pharmacokinetics, patient retention, patient and physician perceptions, and drug-use patterns,” the authors wrote.

The authors found that the majority of studies evaluated switches between biosimilars of infliximab, but they also identified switches between biosimilars of adalimumab, etanercept, and rituximab.

“Some health care providers are hesitant to switch patients from one biosimilar to another biosimilar because of a perceived lack of clinical data on such switches,” Dr. Cohen said in an interview.

The review’s findings – that there were no clinically relevant differences when switching patients from one biosimilar to another – are consistent with the science, Dr. Cohen said. “Physicians should have confidence that the data demonstrate that safety and effectiveness are not impacted if patients switch from one biosimilar to another biosimilar of the same reference biologic,” he said.

Currently, the published data include biosimilars to only four reference biologics. “However, I anticipate additional biosimilar-to-biosimilar switching data will become available in the future,” Dr. Cohen said. “In fact, several new studies have been published in recent months, after the cut-off date for inclusion in our systematic review.”

Switching common in rheumatology, dermatology, and gastroenterology

Biosimilar-to-biosimilar switching was observed most commonly in rheumatology practice, but also was seen in the specialties of dermatology and gastroenterology.

Jeffrey Weinberg, MD, clinical professor of dermatology, Icahn School of Medicine at Mount Sinai, New York City, said in an interview that the study is among the best to date showing that switching biosimilars does not compromise efficacy or safety. 

“I would hypothesize that the interchangeability would apply to psoriasis patients,” Dr. Weinberg said. However, “over the next few years, we will have an increasing number of biosimilars for an increasing number of different molecules. We will need to be vigilant to observe if similar behavior is observed with the biosimilars yet to come.”

Keith Choate, MD, PhD, professor of dermatology, pathology, and genetics, and associate dean for physician-scientist development at Yale University, New Haven, Conn., said that biosimilars have comparable efficacy to the branded medication they replace. “If response is lost to an individual agent, we would not typically then switch to a biosimilar, but would favor another class of therapy or a distinct therapeutic which targets the same pathway.”

When physicians prescribe a biosimilar for rheumatoid arthritis or psoriatic arthritis, in 9 out 10 people, “it’s going to work as well, and it’s not going to cause any more side effects,” said Stanford Shoor, MD, clinical professor of medicine and rheumatology, Stanford (Calif.) University.

The systematic review, even within its limitations, reinforces confidence in the antitumor necrosis factor biosimilars, said Jean-Frederic Colombel, MD, codirector of the Feinstein Inflammatory Bowel Disease Clinical Center at Mount Sinai, New York, and professor of medicine, division of gastroenterology, Icahn School of Medicine at Mount Sinai.

“Still, studies with longer follow-up are needed,” Dr. Colombel said, adding that the remaining questions relate to the efficacy and safety of switching multiple times, which will likely occur in the near future. There will be a “need to provide information to the patient regarding what originator or biosimilar(s) he has been exposed to during the course of his disease.”

Switching will increasingly become the norm, said Miguel Regueiro, MD, chair of the Digestive Disease & Surgery Institute, Cleveland Clinic. In his clinical practice, he has the most experience with Crohn’s disease and ulcerative colitis, and biosimilar-to-biosimilar infliximab switches. “Unless there are data that emerge, I have no concerns with this.” 

He added that it’s an “interesting study that affirms my findings in clinical practice – that one can switch from a biosimilar to biosimilar (of the same reference product).”

The review’s results also make sense from an economic standpoint, said Rajat Bhatt, MD, owner of Prime Rheumatology in Richmond, Tex., and an adjunct faculty member at Caribbean Medical University, Willemstad, Curaçao. “Switching to biosimilars will result in cost savings for the health care system.” Patients on certain insurances also will save by switching to a biosimilar with a lower copay.

However, the review is limited by a relatively small number of studies that have provided primary data on this topic, and most of these were switching from infliximab to a biosimilar for inflammatory bowel disease, said Alfred Kim, MD, PhD, an adult rheumatologist at Barnes-Jewish Hospital, St. Louis, and assistant professor of medicine at Washington University in St. Louis.

As with any meta-analysis evaluating a small number of studies, “broad applicability to all conditions and reference/biosimilar pair can only be assumed. Also, many of the studies used for this meta-analysis are observational, which can introduce a variety of biases that can be difficult to adjust for,” Dr. Kim said. “Nevertheless, these analyses are an important first step in validating the [Food and Drug Administration’s] approach to evaluating biosimilars, as the clinical outcomes are consistent between different biosimilars.”

This systematic review is not enough to prove that all patients will do fine when switching from one biosimilar to another, said Florence Aslinia, MD, a gastroenterologist at the University of Kansas Health System in Kansas City. It’s possible that some patients may not do as well, she said, noting that, in one study of patients with inflammatory bowel disease, 10% of patients on a biosimilar infliximab needed to switch back to the originator infliximab (Remicade, Janssen) because of side effects attributed to the biosimilar. The same thing may or may not happen with biosimilar-to-biosimilar switching, and it requires further study.

The authors did not receive any funding for writing this review. Dr. Cohen is an employee of Sandoz, a division of Novartis. He may own stock in Novartis. Two coauthors are also employees of Sandoz. The other three coauthors reported having financial relationships with numerous pharmaceutical companies, including Sandoz and/or Novartis. Dr. Colombel reported financial relationships with many pharmaceutical companies, including Novartis and other manufacturers of biosimilars. Dr. Regueiro reports financial relationships with numerous pharmaceutical companies, including some manufacturers of biosimilars. Dr. Weinberg reported financial relationships with Celgene, AbbVie, Eli Lilly, and Novartis. Kim reports financial relationships with GlaxoSmithKline, Pfizer, and AstraZeneca. Dr. Aslinia, Dr. Shoor, Dr. Choate, and Dr. Bhatt reported no relevant financial relationships.

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

Switching from one biosimilar medication to another is safe and effective, a new systematic review indicates, even though this clinical practice is not governed by current health authority regulations or guidance.

“No reduction in effectiveness or increase in adverse events was detected in biosimilar-to-biosimilar switching studies conducted to date,” the review’s authors noted in their study, published online in BioDrugs.

“The possibility of multiple switches between biosimilars of the same reference biologic is already a reality, and these types of switches are expected to become more common in the future. ... Although it is not covered by current health authority regulations or guidance,” added the authors, led by Hillel P. Cohen, PhD, executive director of scientific affairs at Sandoz, a division of Novartis.

The researchers searched electronic databases through December 2021 and found 23 observational studies that met their search criteria, of which 13 were published in peer-reviewed journals; the remainder appeared in abstract form. The studies totaled 3,657 patients. The researchers did not identify any randomized clinical trials.

“The studies were heterogeneous in size, design, and endpoints, providing data on safety, effectiveness, immunogenicity, pharmacokinetics, patient retention, patient and physician perceptions, and drug-use patterns,” the authors wrote.

The authors found that the majority of studies evaluated switches between biosimilars of infliximab, but they also identified switches between biosimilars of adalimumab, etanercept, and rituximab.

“Some health care providers are hesitant to switch patients from one biosimilar to another biosimilar because of a perceived lack of clinical data on such switches,” Dr. Cohen said in an interview.

The review’s findings – that there were no clinically relevant differences when switching patients from one biosimilar to another – are consistent with the science, Dr. Cohen said. “Physicians should have confidence that the data demonstrate that safety and effectiveness are not impacted if patients switch from one biosimilar to another biosimilar of the same reference biologic,” he said.

Currently, the published data include biosimilars to only four reference biologics. “However, I anticipate additional biosimilar-to-biosimilar switching data will become available in the future,” Dr. Cohen said. “In fact, several new studies have been published in recent months, after the cut-off date for inclusion in our systematic review.”

Switching common in rheumatology, dermatology, and gastroenterology

Biosimilar-to-biosimilar switching was observed most commonly in rheumatology practice, but also was seen in the specialties of dermatology and gastroenterology.

Jeffrey Weinberg, MD, clinical professor of dermatology, Icahn School of Medicine at Mount Sinai, New York City, said in an interview that the study is among the best to date showing that switching biosimilars does not compromise efficacy or safety. 

“I would hypothesize that the interchangeability would apply to psoriasis patients,” Dr. Weinberg said. However, “over the next few years, we will have an increasing number of biosimilars for an increasing number of different molecules. We will need to be vigilant to observe if similar behavior is observed with the biosimilars yet to come.”

Keith Choate, MD, PhD, professor of dermatology, pathology, and genetics, and associate dean for physician-scientist development at Yale University, New Haven, Conn., said that biosimilars have comparable efficacy to the branded medication they replace. “If response is lost to an individual agent, we would not typically then switch to a biosimilar, but would favor another class of therapy or a distinct therapeutic which targets the same pathway.”

When physicians prescribe a biosimilar for rheumatoid arthritis or psoriatic arthritis, in 9 out 10 people, “it’s going to work as well, and it’s not going to cause any more side effects,” said Stanford Shoor, MD, clinical professor of medicine and rheumatology, Stanford (Calif.) University.

The systematic review, even within its limitations, reinforces confidence in the antitumor necrosis factor biosimilars, said Jean-Frederic Colombel, MD, codirector of the Feinstein Inflammatory Bowel Disease Clinical Center at Mount Sinai, New York, and professor of medicine, division of gastroenterology, Icahn School of Medicine at Mount Sinai.

“Still, studies with longer follow-up are needed,” Dr. Colombel said, adding that the remaining questions relate to the efficacy and safety of switching multiple times, which will likely occur in the near future. There will be a “need to provide information to the patient regarding what originator or biosimilar(s) he has been exposed to during the course of his disease.”

Switching will increasingly become the norm, said Miguel Regueiro, MD, chair of the Digestive Disease & Surgery Institute, Cleveland Clinic. In his clinical practice, he has the most experience with Crohn’s disease and ulcerative colitis, and biosimilar-to-biosimilar infliximab switches. “Unless there are data that emerge, I have no concerns with this.” 

He added that it’s an “interesting study that affirms my findings in clinical practice – that one can switch from a biosimilar to biosimilar (of the same reference product).”

The review’s results also make sense from an economic standpoint, said Rajat Bhatt, MD, owner of Prime Rheumatology in Richmond, Tex., and an adjunct faculty member at Caribbean Medical University, Willemstad, Curaçao. “Switching to biosimilars will result in cost savings for the health care system.” Patients on certain insurances also will save by switching to a biosimilar with a lower copay.

However, the review is limited by a relatively small number of studies that have provided primary data on this topic, and most of these were switching from infliximab to a biosimilar for inflammatory bowel disease, said Alfred Kim, MD, PhD, an adult rheumatologist at Barnes-Jewish Hospital, St. Louis, and assistant professor of medicine at Washington University in St. Louis.

As with any meta-analysis evaluating a small number of studies, “broad applicability to all conditions and reference/biosimilar pair can only be assumed. Also, many of the studies used for this meta-analysis are observational, which can introduce a variety of biases that can be difficult to adjust for,” Dr. Kim said. “Nevertheless, these analyses are an important first step in validating the [Food and Drug Administration’s] approach to evaluating biosimilars, as the clinical outcomes are consistent between different biosimilars.”

This systematic review is not enough to prove that all patients will do fine when switching from one biosimilar to another, said Florence Aslinia, MD, a gastroenterologist at the University of Kansas Health System in Kansas City. It’s possible that some patients may not do as well, she said, noting that, in one study of patients with inflammatory bowel disease, 10% of patients on a biosimilar infliximab needed to switch back to the originator infliximab (Remicade, Janssen) because of side effects attributed to the biosimilar. The same thing may or may not happen with biosimilar-to-biosimilar switching, and it requires further study.

The authors did not receive any funding for writing this review. Dr. Cohen is an employee of Sandoz, a division of Novartis. He may own stock in Novartis. Two coauthors are also employees of Sandoz. The other three coauthors reported having financial relationships with numerous pharmaceutical companies, including Sandoz and/or Novartis. Dr. Colombel reported financial relationships with many pharmaceutical companies, including Novartis and other manufacturers of biosimilars. Dr. Regueiro reports financial relationships with numerous pharmaceutical companies, including some manufacturers of biosimilars. Dr. Weinberg reported financial relationships with Celgene, AbbVie, Eli Lilly, and Novartis. Kim reports financial relationships with GlaxoSmithKline, Pfizer, and AstraZeneca. Dr. Aslinia, Dr. Shoor, Dr. Choate, and Dr. Bhatt reported no relevant financial relationships.

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

Switching from one biosimilar medication to another is safe and effective, a new systematic review indicates, even though this clinical practice is not governed by current health authority regulations or guidance.

“No reduction in effectiveness or increase in adverse events was detected in biosimilar-to-biosimilar switching studies conducted to date,” the review’s authors noted in their study, published online in BioDrugs.

“The possibility of multiple switches between biosimilars of the same reference biologic is already a reality, and these types of switches are expected to become more common in the future. ... Although it is not covered by current health authority regulations or guidance,” added the authors, led by Hillel P. Cohen, PhD, executive director of scientific affairs at Sandoz, a division of Novartis.

The researchers searched electronic databases through December 2021 and found 23 observational studies that met their search criteria, of which 13 were published in peer-reviewed journals; the remainder appeared in abstract form. The studies totaled 3,657 patients. The researchers did not identify any randomized clinical trials.

“The studies were heterogeneous in size, design, and endpoints, providing data on safety, effectiveness, immunogenicity, pharmacokinetics, patient retention, patient and physician perceptions, and drug-use patterns,” the authors wrote.

The authors found that the majority of studies evaluated switches between biosimilars of infliximab, but they also identified switches between biosimilars of adalimumab, etanercept, and rituximab.

“Some health care providers are hesitant to switch patients from one biosimilar to another biosimilar because of a perceived lack of clinical data on such switches,” Dr. Cohen said in an interview.

The review’s findings – that there were no clinically relevant differences when switching patients from one biosimilar to another – are consistent with the science, Dr. Cohen said. “Physicians should have confidence that the data demonstrate that safety and effectiveness are not impacted if patients switch from one biosimilar to another biosimilar of the same reference biologic,” he said.

Currently, the published data include biosimilars to only four reference biologics. “However, I anticipate additional biosimilar-to-biosimilar switching data will become available in the future,” Dr. Cohen said. “In fact, several new studies have been published in recent months, after the cut-off date for inclusion in our systematic review.”

Switching common in rheumatology, dermatology, and gastroenterology

Biosimilar-to-biosimilar switching was observed most commonly in rheumatology practice, but also was seen in the specialties of dermatology and gastroenterology.

Jeffrey Weinberg, MD, clinical professor of dermatology, Icahn School of Medicine at Mount Sinai, New York City, said in an interview that the study is among the best to date showing that switching biosimilars does not compromise efficacy or safety. 

“I would hypothesize that the interchangeability would apply to psoriasis patients,” Dr. Weinberg said. However, “over the next few years, we will have an increasing number of biosimilars for an increasing number of different molecules. We will need to be vigilant to observe if similar behavior is observed with the biosimilars yet to come.”

Keith Choate, MD, PhD, professor of dermatology, pathology, and genetics, and associate dean for physician-scientist development at Yale University, New Haven, Conn., said that biosimilars have comparable efficacy to the branded medication they replace. “If response is lost to an individual agent, we would not typically then switch to a biosimilar, but would favor another class of therapy or a distinct therapeutic which targets the same pathway.”

When physicians prescribe a biosimilar for rheumatoid arthritis or psoriatic arthritis, in 9 out 10 people, “it’s going to work as well, and it’s not going to cause any more side effects,” said Stanford Shoor, MD, clinical professor of medicine and rheumatology, Stanford (Calif.) University.

The systematic review, even within its limitations, reinforces confidence in the antitumor necrosis factor biosimilars, said Jean-Frederic Colombel, MD, codirector of the Feinstein Inflammatory Bowel Disease Clinical Center at Mount Sinai, New York, and professor of medicine, division of gastroenterology, Icahn School of Medicine at Mount Sinai.

“Still, studies with longer follow-up are needed,” Dr. Colombel said, adding that the remaining questions relate to the efficacy and safety of switching multiple times, which will likely occur in the near future. There will be a “need to provide information to the patient regarding what originator or biosimilar(s) he has been exposed to during the course of his disease.”

Switching will increasingly become the norm, said Miguel Regueiro, MD, chair of the Digestive Disease & Surgery Institute, Cleveland Clinic. In his clinical practice, he has the most experience with Crohn’s disease and ulcerative colitis, and biosimilar-to-biosimilar infliximab switches. “Unless there are data that emerge, I have no concerns with this.” 

He added that it’s an “interesting study that affirms my findings in clinical practice – that one can switch from a biosimilar to biosimilar (of the same reference product).”

The review’s results also make sense from an economic standpoint, said Rajat Bhatt, MD, owner of Prime Rheumatology in Richmond, Tex., and an adjunct faculty member at Caribbean Medical University, Willemstad, Curaçao. “Switching to biosimilars will result in cost savings for the health care system.” Patients on certain insurances also will save by switching to a biosimilar with a lower copay.

However, the review is limited by a relatively small number of studies that have provided primary data on this topic, and most of these were switching from infliximab to a biosimilar for inflammatory bowel disease, said Alfred Kim, MD, PhD, an adult rheumatologist at Barnes-Jewish Hospital, St. Louis, and assistant professor of medicine at Washington University in St. Louis.

As with any meta-analysis evaluating a small number of studies, “broad applicability to all conditions and reference/biosimilar pair can only be assumed. Also, many of the studies used for this meta-analysis are observational, which can introduce a variety of biases that can be difficult to adjust for,” Dr. Kim said. “Nevertheless, these analyses are an important first step in validating the [Food and Drug Administration’s] approach to evaluating biosimilars, as the clinical outcomes are consistent between different biosimilars.”

This systematic review is not enough to prove that all patients will do fine when switching from one biosimilar to another, said Florence Aslinia, MD, a gastroenterologist at the University of Kansas Health System in Kansas City. It’s possible that some patients may not do as well, she said, noting that, in one study of patients with inflammatory bowel disease, 10% of patients on a biosimilar infliximab needed to switch back to the originator infliximab (Remicade, Janssen) because of side effects attributed to the biosimilar. The same thing may or may not happen with biosimilar-to-biosimilar switching, and it requires further study.

The authors did not receive any funding for writing this review. Dr. Cohen is an employee of Sandoz, a division of Novartis. He may own stock in Novartis. Two coauthors are also employees of Sandoz. The other three coauthors reported having financial relationships with numerous pharmaceutical companies, including Sandoz and/or Novartis. Dr. Colombel reported financial relationships with many pharmaceutical companies, including Novartis and other manufacturers of biosimilars. Dr. Regueiro reports financial relationships with numerous pharmaceutical companies, including some manufacturers of biosimilars. Dr. Weinberg reported financial relationships with Celgene, AbbVie, Eli Lilly, and Novartis. Kim reports financial relationships with GlaxoSmithKline, Pfizer, and AstraZeneca. Dr. Aslinia, Dr. Shoor, Dr. Choate, and Dr. Bhatt reported no relevant financial relationships.

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

I’m pretty sure my ancestors came from Europe. And, as far as I know, I have no relatives in Australia. But, I must have some cosmic relationship with the Land Down Under because as I review articles for these columns I have an uncanny attraction to those coming out of Australia. Most of them are about sleep, one of my obsessions, and in general they address simple questions that no one has thought to ask.

My most recent Australia-based nugget appeared in the August edition of Pediatrics.

The researchers in Sidney were seeking to define “growing pains” by embarking on an extensive review of the medical literature. Beginning with thousands of articles, they winnowed these down to 145 studies. They found “there was extremely poor consensus between studies.” The most consistent components were the lower limb, bilaterality, evening onset, a normal physical assessment, and an episodic or recurrent course. However, all of these factors were mentioned in 50% or less of the articles they reviewed. The investigators wisely concluded that clinicians “should be wary of relying on the diagnosis to direct treatment decisions.”

This may seem like one small step for pediatrics. You may have reassured parents that none of your patients ever died of “growing pains” and the condition would eventually resolve. Hopefully, you were correct and that your case rate fatality is zero. But I suspect it wouldn’t take too long to unearth a wealth of malpractices cases in which another pediatrician’s patient died with an illness whose eventual discovery was tragically delayed by a period of false reassurance and diagnosis that the child merely had growing pains.

I can’t remember which of my sage instructors told me to never use “growing pains” as a diagnosis. It may have just been something I stumbled upon as my clinical experience grew. While holding firm to my commitment to never use it as a diagnosis, it became abundantly clear that I was seeing a large group of children (toddlers to early adolescents) who were experiencing lower leg pains in the early evening, often bad enough to wake them.

It took a bit longer to discover that most often these painful episodes occurred in children who were acutely or chronically sleep deprived. Occasionally, the pain would come on days in which the child had been unusually physically active. However, in most cases there was little correlation with lower limb activity.

I will admit that my observations were colored by my growing obsession that sleep deprivation is the root of many evils, including the phenomenon known as attention-deficit/hyperactivity disorder. I was even bold enough to include it in my one of the books I have written (Is My Child Overtired? Simon & Schuster, 2001). Nonetheless, I am still convinced that every investigation of a child with evening leg pains should include a thorough history of the child’s sleep history.

The bottom line is that these Australian researchers have done us a great favor with their research. However, I think they should have made a bolder statement in their conclusion. It is clear to me that “growing pains” should be removed as a diagnosis and no longer be reimbursed by third-party payers.

The void created by that action should spur some research into a better-defined diagnosis of the condition. If you want to use my tack and label it “nocturnal leg pains of childhood” and suggest better sleep hygiene, I will be flattered. But more importantly, take the time to take a good history, do a thorough exam, and then follow up, follow up, follow up, until the problem resolves.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

I’m pretty sure my ancestors came from Europe. And, as far as I know, I have no relatives in Australia. But, I must have some cosmic relationship with the Land Down Under because as I review articles for these columns I have an uncanny attraction to those coming out of Australia. Most of them are about sleep, one of my obsessions, and in general they address simple questions that no one has thought to ask.

My most recent Australia-based nugget appeared in the August edition of Pediatrics.

The researchers in Sidney were seeking to define “growing pains” by embarking on an extensive review of the medical literature. Beginning with thousands of articles, they winnowed these down to 145 studies. They found “there was extremely poor consensus between studies.” The most consistent components were the lower limb, bilaterality, evening onset, a normal physical assessment, and an episodic or recurrent course. However, all of these factors were mentioned in 50% or less of the articles they reviewed. The investigators wisely concluded that clinicians “should be wary of relying on the diagnosis to direct treatment decisions.”

This may seem like one small step for pediatrics. You may have reassured parents that none of your patients ever died of “growing pains” and the condition would eventually resolve. Hopefully, you were correct and that your case rate fatality is zero. But I suspect it wouldn’t take too long to unearth a wealth of malpractices cases in which another pediatrician’s patient died with an illness whose eventual discovery was tragically delayed by a period of false reassurance and diagnosis that the child merely had growing pains.

I can’t remember which of my sage instructors told me to never use “growing pains” as a diagnosis. It may have just been something I stumbled upon as my clinical experience grew. While holding firm to my commitment to never use it as a diagnosis, it became abundantly clear that I was seeing a large group of children (toddlers to early adolescents) who were experiencing lower leg pains in the early evening, often bad enough to wake them.

It took a bit longer to discover that most often these painful episodes occurred in children who were acutely or chronically sleep deprived. Occasionally, the pain would come on days in which the child had been unusually physically active. However, in most cases there was little correlation with lower limb activity.

I will admit that my observations were colored by my growing obsession that sleep deprivation is the root of many evils, including the phenomenon known as attention-deficit/hyperactivity disorder. I was even bold enough to include it in my one of the books I have written (Is My Child Overtired? Simon & Schuster, 2001). Nonetheless, I am still convinced that every investigation of a child with evening leg pains should include a thorough history of the child’s sleep history.

The bottom line is that these Australian researchers have done us a great favor with their research. However, I think they should have made a bolder statement in their conclusion. It is clear to me that “growing pains” should be removed as a diagnosis and no longer be reimbursed by third-party payers.

The void created by that action should spur some research into a better-defined diagnosis of the condition. If you want to use my tack and label it “nocturnal leg pains of childhood” and suggest better sleep hygiene, I will be flattered. But more importantly, take the time to take a good history, do a thorough exam, and then follow up, follow up, follow up, until the problem resolves.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

I’m pretty sure my ancestors came from Europe. And, as far as I know, I have no relatives in Australia. But, I must have some cosmic relationship with the Land Down Under because as I review articles for these columns I have an uncanny attraction to those coming out of Australia. Most of them are about sleep, one of my obsessions, and in general they address simple questions that no one has thought to ask.

My most recent Australia-based nugget appeared in the August edition of Pediatrics.

The researchers in Sidney were seeking to define “growing pains” by embarking on an extensive review of the medical literature. Beginning with thousands of articles, they winnowed these down to 145 studies. They found “there was extremely poor consensus between studies.” The most consistent components were the lower limb, bilaterality, evening onset, a normal physical assessment, and an episodic or recurrent course. However, all of these factors were mentioned in 50% or less of the articles they reviewed. The investigators wisely concluded that clinicians “should be wary of relying on the diagnosis to direct treatment decisions.”

This may seem like one small step for pediatrics. You may have reassured parents that none of your patients ever died of “growing pains” and the condition would eventually resolve. Hopefully, you were correct and that your case rate fatality is zero. But I suspect it wouldn’t take too long to unearth a wealth of malpractices cases in which another pediatrician’s patient died with an illness whose eventual discovery was tragically delayed by a period of false reassurance and diagnosis that the child merely had growing pains.

I can’t remember which of my sage instructors told me to never use “growing pains” as a diagnosis. It may have just been something I stumbled upon as my clinical experience grew. While holding firm to my commitment to never use it as a diagnosis, it became abundantly clear that I was seeing a large group of children (toddlers to early adolescents) who were experiencing lower leg pains in the early evening, often bad enough to wake them.

It took a bit longer to discover that most often these painful episodes occurred in children who were acutely or chronically sleep deprived. Occasionally, the pain would come on days in which the child had been unusually physically active. However, in most cases there was little correlation with lower limb activity.

I will admit that my observations were colored by my growing obsession that sleep deprivation is the root of many evils, including the phenomenon known as attention-deficit/hyperactivity disorder. I was even bold enough to include it in my one of the books I have written (Is My Child Overtired? Simon & Schuster, 2001). Nonetheless, I am still convinced that every investigation of a child with evening leg pains should include a thorough history of the child’s sleep history.

The bottom line is that these Australian researchers have done us a great favor with their research. However, I think they should have made a bolder statement in their conclusion. It is clear to me that “growing pains” should be removed as a diagnosis and no longer be reimbursed by third-party payers.

The void created by that action should spur some research into a better-defined diagnosis of the condition. If you want to use my tack and label it “nocturnal leg pains of childhood” and suggest better sleep hygiene, I will be flattered. But more importantly, take the time to take a good history, do a thorough exam, and then follow up, follow up, follow up, until the problem resolves.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

Fewer than 1 in 3 people infected with hepatitis C virus (HCV) begin receiving treatment within a year of their diagnosis, according to a new report by the Centers for Disease Control and Prevention.

Although HCV infection can be cured in more than 95% of patients with safe, oral medication, many barriers prevent people from receiving the care they need, experts say. These include insurance restrictions and the need for specialist visits.

“If we are going to make an impact against hepatitis C, we need to connect more people to treatments and reduce disparities of access to diagnosis and treatment,” said Carolyn Wester, MD, MPH, director of the CDC’s Division of Viral Hepatitis, during an Aug. 9 press call. “People shouldn’t have to jump over hurdles to access lifesaving treatments.”

The CDC report was published  in Vital Signs.

An estimated 2.2 million Americans are living with HCV infection. The most recent data indicate that new infections increased more than threefold from 2011 to 2019. HCV transmission usually occurs through contact with the blood of an infected person. Today, most people become infected with the virus by sharing needles, syringes, and other equipment used to inject drugs, according to the CDC.

The researchers used a nationwide administrative claims database to identify more than 47,600 adults diagnosed with HCV infection from Jan. 30, 2019 through Oct. 31, 2020. Most patients (79%) were Medicaid recipients, 7% were Medicare patients, and 14% had private insurance. CDC researchers found that just 23% of Medicaid recipients, 28% of Medicare patients, and 35% of patients with private insurance began receiving direct-acting antiviral agents (DAAs) within 360 days of receiving a positive HCV test result. Of those who did receive treatment, most (from 75% to 84%) began receiving treatment within 180 days of their diagnosis.

Among people on Medicaid plans, patients who lived in states with treatment restrictions were 23% less likely to receive timely treatment (adjusted odds ratio, 0.77; 95% confidence interval, 0.74-0.81), compared with those living in states with no restrictions. Medicaid patients who were Black or of another race other than White were also less likely than White patients to be treated for HCV within the same year as their diagnosis. The lowest rates of treatment were among adults younger than 40 years, regardless of insurance type. This age group had the highest rates of new infections.

Actual treatment percentages may be even smaller than the number captured in this study, because the study included patients with continuous insurance coverage, Dr. Wester said, “so in many ways, [these] are the individuals who are set up to have the best access to care and treatment.”

Dr. Wester mentioned several steps that could improve access to DAAs for patients with HCV infection:

• Provide treatment outside of specialist offices, such as primary care and community clinics, substance use treatment centers, and syringe services programs.
• Increase the number of primary care providers offering hepatitis C treatment.
• Provide treatment in as few visits as possible.
• Eliminate restrictions by insurance providers on treatment.

A ‘health injustice’

While DAA treatments are effective, they are also expensive. Generic medications cost around $24,000 for a 12-week course, and some brand-name drugs are estimated to cost more than three times that amount. Many insurance companies, therefore, have treatment restrictions in place, including the following:

• There must be evidence of liver fibrosis for a patient to be treated.
• The doctor prescribing treatment must be a liver specialist or an infectious disease specialist.
• The patient must meet sobriety requirements.
• Treatment requires preauthorization approval from insurance carriers.

These criteria prevent patients from getting the care that they need, said Jonathan Mermin, MD, MPH, director of the CDC’s National Center for HIV, Viral Hepatitis, STD, and TB Prevention, during the press call. “Restricting access to hepatitis C treatment turns an infectious disease into a health injustice,” he added.

Oluwaseun Falade-Nwulia, MBBS, MPH, an infectious disease specialist and assistant professor of medicine at the Johns Hopkins University School of Medicine, Baltimore, emphasized the importance of removing barriers to HCV treatment and expanding HCV care out of specialist offices. She noted that treatment for HCV infection should begin immediately after a patient’s diagnosis. Previously, guidelines recommended waiting 6 months from the time a patient was diagnosed with HCV to begin treatment to see whether the patient’s body could clear the infection on its own. Now, guidelines recommend that after a diagnosis of acute HCV, “HCV treatment should be initiated without awaiting spontaneous resolution.” But some insurance companies still ask for evidence that a patient has been infected for at least 6 months before approving therapy, Dr. Falade-Nwulia noted.

“We have a system that has so many structural barriers for patients who we know already have so many social determinants of health working against them to access any health care,” she said. “I think it’s doubly devastating that patients that can actually get to a provider and get a prescription may still not have access to [the medication] because of structural barriers, such as restrictions based on a need to prove chronicity.”

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

Fewer than 1 in 3 people infected with hepatitis C virus (HCV) begin receiving treatment within a year of their diagnosis, according to a new report by the Centers for Disease Control and Prevention.

Although HCV infection can be cured in more than 95% of patients with safe, oral medication, many barriers prevent people from receiving the care they need, experts say. These include insurance restrictions and the need for specialist visits.

“If we are going to make an impact against hepatitis C, we need to connect more people to treatments and reduce disparities of access to diagnosis and treatment,” said Carolyn Wester, MD, MPH, director of the CDC’s Division of Viral Hepatitis, during an Aug. 9 press call. “People shouldn’t have to jump over hurdles to access lifesaving treatments.”

The CDC report was published  in Vital Signs.

An estimated 2.2 million Americans are living with HCV infection. The most recent data indicate that new infections increased more than threefold from 2011 to 2019. HCV transmission usually occurs through contact with the blood of an infected person. Today, most people become infected with the virus by sharing needles, syringes, and other equipment used to inject drugs, according to the CDC.

The researchers used a nationwide administrative claims database to identify more than 47,600 adults diagnosed with HCV infection from Jan. 30, 2019 through Oct. 31, 2020. Most patients (79%) were Medicaid recipients, 7% were Medicare patients, and 14% had private insurance. CDC researchers found that just 23% of Medicaid recipients, 28% of Medicare patients, and 35% of patients with private insurance began receiving direct-acting antiviral agents (DAAs) within 360 days of receiving a positive HCV test result. Of those who did receive treatment, most (from 75% to 84%) began receiving treatment within 180 days of their diagnosis.

Among people on Medicaid plans, patients who lived in states with treatment restrictions were 23% less likely to receive timely treatment (adjusted odds ratio, 0.77; 95% confidence interval, 0.74-0.81), compared with those living in states with no restrictions. Medicaid patients who were Black or of another race other than White were also less likely than White patients to be treated for HCV within the same year as their diagnosis. The lowest rates of treatment were among adults younger than 40 years, regardless of insurance type. This age group had the highest rates of new infections.

Actual treatment percentages may be even smaller than the number captured in this study, because the study included patients with continuous insurance coverage, Dr. Wester said, “so in many ways, [these] are the individuals who are set up to have the best access to care and treatment.”

Dr. Wester mentioned several steps that could improve access to DAAs for patients with HCV infection:

• Provide treatment outside of specialist offices, such as primary care and community clinics, substance use treatment centers, and syringe services programs.
• Increase the number of primary care providers offering hepatitis C treatment.
• Provide treatment in as few visits as possible.
• Eliminate restrictions by insurance providers on treatment.

A ‘health injustice’

While DAA treatments are effective, they are also expensive. Generic medications cost around $24,000 for a 12-week course, and some brand-name drugs are estimated to cost more than three times that amount. Many insurance companies, therefore, have treatment restrictions in place, including the following:

• There must be evidence of liver fibrosis for a patient to be treated.
• The doctor prescribing treatment must be a liver specialist or an infectious disease specialist.
• The patient must meet sobriety requirements.
• Treatment requires preauthorization approval from insurance carriers.

These criteria prevent patients from getting the care that they need, said Jonathan Mermin, MD, MPH, director of the CDC’s National Center for HIV, Viral Hepatitis, STD, and TB Prevention, during the press call. “Restricting access to hepatitis C treatment turns an infectious disease into a health injustice,” he added.

Oluwaseun Falade-Nwulia, MBBS, MPH, an infectious disease specialist and assistant professor of medicine at the Johns Hopkins University School of Medicine, Baltimore, emphasized the importance of removing barriers to HCV treatment and expanding HCV care out of specialist offices. She noted that treatment for HCV infection should begin immediately after a patient’s diagnosis. Previously, guidelines recommended waiting 6 months from the time a patient was diagnosed with HCV to begin treatment to see whether the patient’s body could clear the infection on its own. Now, guidelines recommend that after a diagnosis of acute HCV, “HCV treatment should be initiated without awaiting spontaneous resolution.” But some insurance companies still ask for evidence that a patient has been infected for at least 6 months before approving therapy, Dr. Falade-Nwulia noted.

“We have a system that has so many structural barriers for patients who we know already have so many social determinants of health working against them to access any health care,” she said. “I think it’s doubly devastating that patients that can actually get to a provider and get a prescription may still not have access to [the medication] because of structural barriers, such as restrictions based on a need to prove chronicity.”

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

Fewer than 1 in 3 people infected with hepatitis C virus (HCV) begin receiving treatment within a year of their diagnosis, according to a new report by the Centers for Disease Control and Prevention.

Although HCV infection can be cured in more than 95% of patients with safe, oral medication, many barriers prevent people from receiving the care they need, experts say. These include insurance restrictions and the need for specialist visits.

“If we are going to make an impact against hepatitis C, we need to connect more people to treatments and reduce disparities of access to diagnosis and treatment,” said Carolyn Wester, MD, MPH, director of the CDC’s Division of Viral Hepatitis, during an Aug. 9 press call. “People shouldn’t have to jump over hurdles to access lifesaving treatments.”

The CDC report was published  in Vital Signs.

An estimated 2.2 million Americans are living with HCV infection. The most recent data indicate that new infections increased more than threefold from 2011 to 2019. HCV transmission usually occurs through contact with the blood of an infected person. Today, most people become infected with the virus by sharing needles, syringes, and other equipment used to inject drugs, according to the CDC.

The researchers used a nationwide administrative claims database to identify more than 47,600 adults diagnosed with HCV infection from Jan. 30, 2019 through Oct. 31, 2020. Most patients (79%) were Medicaid recipients, 7% were Medicare patients, and 14% had private insurance. CDC researchers found that just 23% of Medicaid recipients, 28% of Medicare patients, and 35% of patients with private insurance began receiving direct-acting antiviral agents (DAAs) within 360 days of receiving a positive HCV test result. Of those who did receive treatment, most (from 75% to 84%) began receiving treatment within 180 days of their diagnosis.

Among people on Medicaid plans, patients who lived in states with treatment restrictions were 23% less likely to receive timely treatment (adjusted odds ratio, 0.77; 95% confidence interval, 0.74-0.81), compared with those living in states with no restrictions. Medicaid patients who were Black or of another race other than White were also less likely than White patients to be treated for HCV within the same year as their diagnosis. The lowest rates of treatment were among adults younger than 40 years, regardless of insurance type. This age group had the highest rates of new infections.

Actual treatment percentages may be even smaller than the number captured in this study, because the study included patients with continuous insurance coverage, Dr. Wester said, “so in many ways, [these] are the individuals who are set up to have the best access to care and treatment.”

Dr. Wester mentioned several steps that could improve access to DAAs for patients with HCV infection:

• Provide treatment outside of specialist offices, such as primary care and community clinics, substance use treatment centers, and syringe services programs.
• Increase the number of primary care providers offering hepatitis C treatment.
• Provide treatment in as few visits as possible.
• Eliminate restrictions by insurance providers on treatment.

A ‘health injustice’

While DAA treatments are effective, they are also expensive. Generic medications cost around $24,000 for a 12-week course, and some brand-name drugs are estimated to cost more than three times that amount. Many insurance companies, therefore, have treatment restrictions in place, including the following:

• There must be evidence of liver fibrosis for a patient to be treated.
• The doctor prescribing treatment must be a liver specialist or an infectious disease specialist.
• The patient must meet sobriety requirements.
• Treatment requires preauthorization approval from insurance carriers.

These criteria prevent patients from getting the care that they need, said Jonathan Mermin, MD, MPH, director of the CDC’s National Center for HIV, Viral Hepatitis, STD, and TB Prevention, during the press call. “Restricting access to hepatitis C treatment turns an infectious disease into a health injustice,” he added.

Oluwaseun Falade-Nwulia, MBBS, MPH, an infectious disease specialist and assistant professor of medicine at the Johns Hopkins University School of Medicine, Baltimore, emphasized the importance of removing barriers to HCV treatment and expanding HCV care out of specialist offices. She noted that treatment for HCV infection should begin immediately after a patient’s diagnosis. Previously, guidelines recommended waiting 6 months from the time a patient was diagnosed with HCV to begin treatment to see whether the patient’s body could clear the infection on its own. Now, guidelines recommend that after a diagnosis of acute HCV, “HCV treatment should be initiated without awaiting spontaneous resolution.” But some insurance companies still ask for evidence that a patient has been infected for at least 6 months before approving therapy, Dr. Falade-Nwulia noted.

“We have a system that has so many structural barriers for patients who we know already have so many social determinants of health working against them to access any health care,” she said. “I think it’s doubly devastating that patients that can actually get to a provider and get a prescription may still not have access to [the medication] because of structural barriers, such as restrictions based on a need to prove chronicity.”

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

Two very different sets of clinical evidence have offered new twists on how nonadherence to cardiovascular medicines not only leads to suboptimal outcomes, but also complicates the data from clinical studies.

One study, a subanalysis of a major trial, outlined how taking more than the assigned therapy – that is, nonadherence by taking too much rather than too little – skewed results. The other was a trial demonstrating that early use of an invasive procedure is not a strategy to compensate for nonadherence to guideline-directed medical therapy (GDMT).

Bruce Jancin/Frontline Medical News

“Both studies provide a fresh reminder that nonadherence is a significant problem in cardiology overall, but also in the trial setting when we are trying to interpret study results,” explained Usam Baber, MD, director of interventional cardiology, University of Oklahoma Health, Oklahoma City, coauthor of an editorial accompanying the two published studies.

Dr. Baber was the first author of a unifying editorial that addressed the issues raised by each. In an interview, Dr. Baber said the studies had unique take-home messages but together highlight important issues of nonadherence.
 

MASTER DAPT: Too much medicine

The subanalysis was performed on data generated by MASTER DAPT, a study evaluating whether a relatively short course of dual-antiplatelet therapy (DAPT) in patients at high risk of bleeding could preserve protection against major adverse cardiovascular events (MACE) while reducing risk of adverse events. The problem was that nonadherence muddied the primary message.

In MASTER DAPT, 1 month of DAPT was compared with a standard therapy of at least 2 additional months of DAPT following revascularization and placement of a biodegradable polymer stent. Enrollment in the study was restricted to those with a high risk of bleeding, the report of the primary results showed.

The major message of MASTER DAPT was that the abbreviated course of DAPT was noninferior for preventing MACE but resulted in lower rates of clinically relevant bleeding in those patients without an indication for oral anticoagulation (OAC). In the subgroup with an indication for OAC, there was no bleeding benefit.

However, when the results were reexamined in the context of adherence, the benefit of the shorter course was found to be underestimated. Relative to 9.4% in the standard-therapy arm, the nonadherence rate in the experimental arm was 20.2%, most of whom did not stop therapy at 1 month. They instead remained on the antiplatelet therapy, failing to adhere to the study protocol.

This form of nonadherence, taking more DAPT than assigned, was particularly common in the group with an indication for oral anticoagulation (OAC). In this group, nearly 25% assigned to an abbreviated course remained on DAPT for more than 6 months.

In the intention-to-treat analysis, there was no difference between abbreviated and standard DAPT for MACE whether or not patients had an indication for OAC. In other words, the new analysis showed a reduced risk of bleeding among all patients, whether taking OAC or not after controlling for nonadherence.

In addition, this MASTER DAPT analysis found that a high proportion of patients taking OAC did not discontinue their single-antiplatelet therapy (SAPT) after 6 months as specified.

When correcting for this failure to adhere to the MASTER DAPT protocol in a patient population at high bleeding risk, the new analysis “suggests for the first time that discontinuation of SAPT at 6 months after percutaneous intervention is associated with less bleeding without an increase in ischemic events,” Marco Valgimigli, MD, PhD, director of clinical research, Inselspital University Hospital, Bern, Switzerland, reported in the Journal of the American College of Cardiology.

The findings “reinforce the importance of accounting and correcting for nonadherence” in order to reduce bias in the assessment of treatment effects, according to Dr. Valgimigli, principal investigator of MASTER DAPT and this substudy.

“The first interesting message from this study is that clinicians are reluctant to stop SAPT in these patients even in the setting of a randomized controlled trial,” Dr. Valgimigli said in an interview.

In addition, this substudy, which was prespecified in the MASTER DAPT protocol and employed “a very sophisticated methodology” to control for the effect of adherence, extends the value of a conservative approach to those who are candidates for OAC.

“The main clinical message is that SAPT needs to be discontinued after 6 months in OAC patients, and clinicians need to stop being reluctant to do so,” Dr. Valgimigli said. The data show “prolongation of SAPT increases bleeding risk without decreasing ischemic risk.”

In evaluating trial relevance, regulators prefer ITT analyses, but Dr. Baber pointed out that these can obscure the evidence of risk or benefit of a per-protocol analysis when patients take their medicine as prescribed.

“The technical message is that, when we are trying to apply results of a clinical trial to daily practice, we must understand nonadherence,” Dr. Baber said.

Dr. Baber pointed out that the lack of adherence in the case of MASTER DAPT appears to relate more to clinicians managing the patients than to the patients themselves, but it still speaks to the importance of understanding the effects of treatment in the context of the medicine rather than adherence to the medicine.

ISCHEMIA: Reconsidering adherence

In the ISCHEMIA trial, the goal was to evaluate whether an early invasive intervention might compensate to at least some degree for the persistent problem of nonadherence.

“If you are managing a patient that you know is at high risk of noncompliance, many clinicians are tempted to perform early revascularization. This was my bias. The thinking is that by offering an invasive therapy we are at least doing something to control their disease,” John A. Spertus, MD, clinical director of outcomes research, St. Luke’s Mid America Heart Institute, Kansas City, Mo., explained in an interview.

The study did not support the hypothesis. Patients with chronic coronary disease were randomized to a strategy of angiography and, if indicated, revascularization, or to receive GDMT alone. The health status was followed with the Seattle Angina Questionnaire (SAQ-7).

At 12 months, patients who were adherent to GDMT had better SAQ-7 scores than those who were nonadherent, regardless of the arm to which they were randomized. Conversely, there was no difference in SAQ-7 scores between the two groups when the nonadherent subgroups in each arm were compared.

“I think these data suggest that an interventional therapy does not absolve clinicians from the responsibility of educating patients about the importance of adhering to GDMT,” Dr. Spertus said.

In ISCHEMIA, 4,480 patients were randomized. At baseline assessment 27.8% were nonadherent to GDMT. The baselines SAQ-7 scores were worse in these patients relative to those who were adherent. At 12 months, nonadherence still correlated with worse SAQ-7 scores.

“These data dispel the belief that we might be benefiting nonadherent patients by moving more quickly to invasive procedures,” Dr. Spertus said.

In cardiovascular disease, particularly heart failure, adherence to GDMT has been associated numerous times with improved quality of life, according to Dr. Baber. However, he said, the ability of invasive procedures to modify the adverse impact of poor adherence to GDMT has not been well studied. This ISCHEMIA subanalysis only reinforces the message that GDMT adherence is a meaningful predictor of improved quality of life.

However, urging clinicians to work with patients to improve adherence is not a novel idea, according to Dr. Baber. The unmet need is effective and reliable strategies.

“There are so many different reasons that patients are nonadherent, so there are limited gains by focusing on just one of the issues,” Dr. Baber said. “I think the answer is a patient-centric approach in which clinicians deal with the specific issues facing the patient in front of them. I think there are data go suggest this yields better results.”

These two very different studies also show that poor adherence is an insidious issue. While the MASTER DAPT data reveal how nonadherence confuse trial data, the ISCHEMIA trial shows that some assumptions about circumventing the effects of nonadherence might not be accurate.

According to Dr. Baber, effective strategies to reduce nonadherence are available, but the problem deserves to be addressed more proactively in clinical trials and in patient care.

Dr. Baber reported financial relationships with AstraZeneca and Amgen. Dr. Spertus has financial relationships with Abbott, Bayer, Bristol-Myers Squibb, Corvia, Janssen, Merck, Novartis, Pfizer and Terumo. Dr. Valgimigli has financial relationships with more than 15 pharmaceutical companies, including Terumo, which provided funding for the MASTER DAPT trial.
 

Two very different sets of clinical evidence have offered new twists on how nonadherence to cardiovascular medicines not only leads to suboptimal outcomes, but also complicates the data from clinical studies.

One study, a subanalysis of a major trial, outlined how taking more than the assigned therapy – that is, nonadherence by taking too much rather than too little – skewed results. The other was a trial demonstrating that early use of an invasive procedure is not a strategy to compensate for nonadherence to guideline-directed medical therapy (GDMT).

Bruce Jancin/Frontline Medical News

“Both studies provide a fresh reminder that nonadherence is a significant problem in cardiology overall, but also in the trial setting when we are trying to interpret study results,” explained Usam Baber, MD, director of interventional cardiology, University of Oklahoma Health, Oklahoma City, coauthor of an editorial accompanying the two published studies.

Dr. Baber was the first author of a unifying editorial that addressed the issues raised by each. In an interview, Dr. Baber said the studies had unique take-home messages but together highlight important issues of nonadherence.
 

MASTER DAPT: Too much medicine

The subanalysis was performed on data generated by MASTER DAPT, a study evaluating whether a relatively short course of dual-antiplatelet therapy (DAPT) in patients at high risk of bleeding could preserve protection against major adverse cardiovascular events (MACE) while reducing risk of adverse events. The problem was that nonadherence muddied the primary message.

In MASTER DAPT, 1 month of DAPT was compared with a standard therapy of at least 2 additional months of DAPT following revascularization and placement of a biodegradable polymer stent. Enrollment in the study was restricted to those with a high risk of bleeding, the report of the primary results showed.

The major message of MASTER DAPT was that the abbreviated course of DAPT was noninferior for preventing MACE but resulted in lower rates of clinically relevant bleeding in those patients without an indication for oral anticoagulation (OAC). In the subgroup with an indication for OAC, there was no bleeding benefit.

However, when the results were reexamined in the context of adherence, the benefit of the shorter course was found to be underestimated. Relative to 9.4% in the standard-therapy arm, the nonadherence rate in the experimental arm was 20.2%, most of whom did not stop therapy at 1 month. They instead remained on the antiplatelet therapy, failing to adhere to the study protocol.

This form of nonadherence, taking more DAPT than assigned, was particularly common in the group with an indication for oral anticoagulation (OAC). In this group, nearly 25% assigned to an abbreviated course remained on DAPT for more than 6 months.

In the intention-to-treat analysis, there was no difference between abbreviated and standard DAPT for MACE whether or not patients had an indication for OAC. In other words, the new analysis showed a reduced risk of bleeding among all patients, whether taking OAC or not after controlling for nonadherence.

In addition, this MASTER DAPT analysis found that a high proportion of patients taking OAC did not discontinue their single-antiplatelet therapy (SAPT) after 6 months as specified.

When correcting for this failure to adhere to the MASTER DAPT protocol in a patient population at high bleeding risk, the new analysis “suggests for the first time that discontinuation of SAPT at 6 months after percutaneous intervention is associated with less bleeding without an increase in ischemic events,” Marco Valgimigli, MD, PhD, director of clinical research, Inselspital University Hospital, Bern, Switzerland, reported in the Journal of the American College of Cardiology.

The findings “reinforce the importance of accounting and correcting for nonadherence” in order to reduce bias in the assessment of treatment effects, according to Dr. Valgimigli, principal investigator of MASTER DAPT and this substudy.

“The first interesting message from this study is that clinicians are reluctant to stop SAPT in these patients even in the setting of a randomized controlled trial,” Dr. Valgimigli said in an interview.

In addition, this substudy, which was prespecified in the MASTER DAPT protocol and employed “a very sophisticated methodology” to control for the effect of adherence, extends the value of a conservative approach to those who are candidates for OAC.

“The main clinical message is that SAPT needs to be discontinued after 6 months in OAC patients, and clinicians need to stop being reluctant to do so,” Dr. Valgimigli said. The data show “prolongation of SAPT increases bleeding risk without decreasing ischemic risk.”

In evaluating trial relevance, regulators prefer ITT analyses, but Dr. Baber pointed out that these can obscure the evidence of risk or benefit of a per-protocol analysis when patients take their medicine as prescribed.

“The technical message is that, when we are trying to apply results of a clinical trial to daily practice, we must understand nonadherence,” Dr. Baber said.

Dr. Baber pointed out that the lack of adherence in the case of MASTER DAPT appears to relate more to clinicians managing the patients than to the patients themselves, but it still speaks to the importance of understanding the effects of treatment in the context of the medicine rather than adherence to the medicine.

ISCHEMIA: Reconsidering adherence

In the ISCHEMIA trial, the goal was to evaluate whether an early invasive intervention might compensate to at least some degree for the persistent problem of nonadherence.

“If you are managing a patient that you know is at high risk of noncompliance, many clinicians are tempted to perform early revascularization. This was my bias. The thinking is that by offering an invasive therapy we are at least doing something to control their disease,” John A. Spertus, MD, clinical director of outcomes research, St. Luke’s Mid America Heart Institute, Kansas City, Mo., explained in an interview.

The study did not support the hypothesis. Patients with chronic coronary disease were randomized to a strategy of angiography and, if indicated, revascularization, or to receive GDMT alone. The health status was followed with the Seattle Angina Questionnaire (SAQ-7).

At 12 months, patients who were adherent to GDMT had better SAQ-7 scores than those who were nonadherent, regardless of the arm to which they were randomized. Conversely, there was no difference in SAQ-7 scores between the two groups when the nonadherent subgroups in each arm were compared.

“I think these data suggest that an interventional therapy does not absolve clinicians from the responsibility of educating patients about the importance of adhering to GDMT,” Dr. Spertus said.

In ISCHEMIA, 4,480 patients were randomized. At baseline assessment 27.8% were nonadherent to GDMT. The baselines SAQ-7 scores were worse in these patients relative to those who were adherent. At 12 months, nonadherence still correlated with worse SAQ-7 scores.

“These data dispel the belief that we might be benefiting nonadherent patients by moving more quickly to invasive procedures,” Dr. Spertus said.

In cardiovascular disease, particularly heart failure, adherence to GDMT has been associated numerous times with improved quality of life, according to Dr. Baber. However, he said, the ability of invasive procedures to modify the adverse impact of poor adherence to GDMT has not been well studied. This ISCHEMIA subanalysis only reinforces the message that GDMT adherence is a meaningful predictor of improved quality of life.

However, urging clinicians to work with patients to improve adherence is not a novel idea, according to Dr. Baber. The unmet need is effective and reliable strategies.

“There are so many different reasons that patients are nonadherent, so there are limited gains by focusing on just one of the issues,” Dr. Baber said. “I think the answer is a patient-centric approach in which clinicians deal with the specific issues facing the patient in front of them. I think there are data go suggest this yields better results.”

These two very different studies also show that poor adherence is an insidious issue. While the MASTER DAPT data reveal how nonadherence confuse trial data, the ISCHEMIA trial shows that some assumptions about circumventing the effects of nonadherence might not be accurate.

According to Dr. Baber, effective strategies to reduce nonadherence are available, but the problem deserves to be addressed more proactively in clinical trials and in patient care.

Dr. Baber reported financial relationships with AstraZeneca and Amgen. Dr. Spertus has financial relationships with Abbott, Bayer, Bristol-Myers Squibb, Corvia, Janssen, Merck, Novartis, Pfizer and Terumo. Dr. Valgimigli has financial relationships with more than 15 pharmaceutical companies, including Terumo, which provided funding for the MASTER DAPT trial.
 

Two very different sets of clinical evidence have offered new twists on how nonadherence to cardiovascular medicines not only leads to suboptimal outcomes, but also complicates the data from clinical studies.

One study, a subanalysis of a major trial, outlined how taking more than the assigned therapy – that is, nonadherence by taking too much rather than too little – skewed results. The other was a trial demonstrating that early use of an invasive procedure is not a strategy to compensate for nonadherence to guideline-directed medical therapy (GDMT).

Bruce Jancin/Frontline Medical News

“Both studies provide a fresh reminder that nonadherence is a significant problem in cardiology overall, but also in the trial setting when we are trying to interpret study results,” explained Usam Baber, MD, director of interventional cardiology, University of Oklahoma Health, Oklahoma City, coauthor of an editorial accompanying the two published studies.

Dr. Baber was the first author of a unifying editorial that addressed the issues raised by each. In an interview, Dr. Baber said the studies had unique take-home messages but together highlight important issues of nonadherence.
 

MASTER DAPT: Too much medicine

The subanalysis was performed on data generated by MASTER DAPT, a study evaluating whether a relatively short course of dual-antiplatelet therapy (DAPT) in patients at high risk of bleeding could preserve protection against major adverse cardiovascular events (MACE) while reducing risk of adverse events. The problem was that nonadherence muddied the primary message.

In MASTER DAPT, 1 month of DAPT was compared with a standard therapy of at least 2 additional months of DAPT following revascularization and placement of a biodegradable polymer stent. Enrollment in the study was restricted to those with a high risk of bleeding, the report of the primary results showed.

The major message of MASTER DAPT was that the abbreviated course of DAPT was noninferior for preventing MACE but resulted in lower rates of clinically relevant bleeding in those patients without an indication for oral anticoagulation (OAC). In the subgroup with an indication for OAC, there was no bleeding benefit.

However, when the results were reexamined in the context of adherence, the benefit of the shorter course was found to be underestimated. Relative to 9.4% in the standard-therapy arm, the nonadherence rate in the experimental arm was 20.2%, most of whom did not stop therapy at 1 month. They instead remained on the antiplatelet therapy, failing to adhere to the study protocol.

This form of nonadherence, taking more DAPT than assigned, was particularly common in the group with an indication for oral anticoagulation (OAC). In this group, nearly 25% assigned to an abbreviated course remained on DAPT for more than 6 months.

In the intention-to-treat analysis, there was no difference between abbreviated and standard DAPT for MACE whether or not patients had an indication for OAC. In other words, the new analysis showed a reduced risk of bleeding among all patients, whether taking OAC or not after controlling for nonadherence.

In addition, this MASTER DAPT analysis found that a high proportion of patients taking OAC did not discontinue their single-antiplatelet therapy (SAPT) after 6 months as specified.

When correcting for this failure to adhere to the MASTER DAPT protocol in a patient population at high bleeding risk, the new analysis “suggests for the first time that discontinuation of SAPT at 6 months after percutaneous intervention is associated with less bleeding without an increase in ischemic events,” Marco Valgimigli, MD, PhD, director of clinical research, Inselspital University Hospital, Bern, Switzerland, reported in the Journal of the American College of Cardiology.

The findings “reinforce the importance of accounting and correcting for nonadherence” in order to reduce bias in the assessment of treatment effects, according to Dr. Valgimigli, principal investigator of MASTER DAPT and this substudy.

“The first interesting message from this study is that clinicians are reluctant to stop SAPT in these patients even in the setting of a randomized controlled trial,” Dr. Valgimigli said in an interview.

In addition, this substudy, which was prespecified in the MASTER DAPT protocol and employed “a very sophisticated methodology” to control for the effect of adherence, extends the value of a conservative approach to those who are candidates for OAC.

“The main clinical message is that SAPT needs to be discontinued after 6 months in OAC patients, and clinicians need to stop being reluctant to do so,” Dr. Valgimigli said. The data show “prolongation of SAPT increases bleeding risk without decreasing ischemic risk.”

In evaluating trial relevance, regulators prefer ITT analyses, but Dr. Baber pointed out that these can obscure the evidence of risk or benefit of a per-protocol analysis when patients take their medicine as prescribed.

“The technical message is that, when we are trying to apply results of a clinical trial to daily practice, we must understand nonadherence,” Dr. Baber said.

Dr. Baber pointed out that the lack of adherence in the case of MASTER DAPT appears to relate more to clinicians managing the patients than to the patients themselves, but it still speaks to the importance of understanding the effects of treatment in the context of the medicine rather than adherence to the medicine.

ISCHEMIA: Reconsidering adherence

In the ISCHEMIA trial, the goal was to evaluate whether an early invasive intervention might compensate to at least some degree for the persistent problem of nonadherence.

“If you are managing a patient that you know is at high risk of noncompliance, many clinicians are tempted to perform early revascularization. This was my bias. The thinking is that by offering an invasive therapy we are at least doing something to control their disease,” John A. Spertus, MD, clinical director of outcomes research, St. Luke’s Mid America Heart Institute, Kansas City, Mo., explained in an interview.

The study did not support the hypothesis. Patients with chronic coronary disease were randomized to a strategy of angiography and, if indicated, revascularization, or to receive GDMT alone. The health status was followed with the Seattle Angina Questionnaire (SAQ-7).

At 12 months, patients who were adherent to GDMT had better SAQ-7 scores than those who were nonadherent, regardless of the arm to which they were randomized. Conversely, there was no difference in SAQ-7 scores between the two groups when the nonadherent subgroups in each arm were compared.

“I think these data suggest that an interventional therapy does not absolve clinicians from the responsibility of educating patients about the importance of adhering to GDMT,” Dr. Spertus said.

In ISCHEMIA, 4,480 patients were randomized. At baseline assessment 27.8% were nonadherent to GDMT. The baselines SAQ-7 scores were worse in these patients relative to those who were adherent. At 12 months, nonadherence still correlated with worse SAQ-7 scores.

“These data dispel the belief that we might be benefiting nonadherent patients by moving more quickly to invasive procedures,” Dr. Spertus said.

In cardiovascular disease, particularly heart failure, adherence to GDMT has been associated numerous times with improved quality of life, according to Dr. Baber. However, he said, the ability of invasive procedures to modify the adverse impact of poor adherence to GDMT has not been well studied. This ISCHEMIA subanalysis only reinforces the message that GDMT adherence is a meaningful predictor of improved quality of life.

However, urging clinicians to work with patients to improve adherence is not a novel idea, according to Dr. Baber. The unmet need is effective and reliable strategies.

“There are so many different reasons that patients are nonadherent, so there are limited gains by focusing on just one of the issues,” Dr. Baber said. “I think the answer is a patient-centric approach in which clinicians deal with the specific issues facing the patient in front of them. I think there are data go suggest this yields better results.”

These two very different studies also show that poor adherence is an insidious issue. While the MASTER DAPT data reveal how nonadherence confuse trial data, the ISCHEMIA trial shows that some assumptions about circumventing the effects of nonadherence might not be accurate.

According to Dr. Baber, effective strategies to reduce nonadherence are available, but the problem deserves to be addressed more proactively in clinical trials and in patient care.

Dr. Baber reported financial relationships with AstraZeneca and Amgen. Dr. Spertus has financial relationships with Abbott, Bayer, Bristol-Myers Squibb, Corvia, Janssen, Merck, Novartis, Pfizer and Terumo. Dr. Valgimigli has financial relationships with more than 15 pharmaceutical companies, including Terumo, which provided funding for the MASTER DAPT trial.
 

Polio virus has been discovered in New York City’s sewers, suggesting that the virus is circulating in the city, New York’s health authorities said Aug. 12.

The detection of polio in NYC is alarming but not surprising, said New York State Health Commissioner Mary Bassett, MD, MPH.

“For every one case of paralytic polio identified, hundreds more may be undetected,” Dr. Bassett said. “The best way to keep adults and children polio-free is through safe and effective immunization.”

Polio can cause permanent paralysis of limbs and even death in some cases. Before this outbreak, the last case of polio in the United States was in 2013.

The announcement came after a man in Rockland County, New York, north of the city, was stricken with polio at the end of July and paralyzed.

Now, health officials fear that the detection of polio in NYC wastewater could bring other cases of paralytic polio.

“It is not surprising, since this is something already seen with Rockland County,” Amesh Adalja, MD, senior scholar at the Johns Hopkins Center for Health Security in Baltimore, told this news organization. “This is solely the result of under-vaccination in the area. I think it’s likely that we will see a few paralytic cases but not a high number.”
 

Vaccinations declined in pandemic

Among the worries is that vaccination rates across New York City dipped during the pandemic because pediatrician visits were postponed.

In New York City, the overall rate of polio vaccination among children aged 5 years or younger is 86%. Still, in some city ZIP codes, fewer than two-thirds of children in that age group have received the full dosage, which worries health officials.

However, most adults were vaccinated against polio as children.

Across New York state, nearly 80% of people have been vaccinated, according to data from the state public health department. Those who are unvaccinated are at risk, but the polio vaccine is nearly 100% effective in people who are fully immunized.

New York health authorities are calling on those who are unvaccinated to get their shots immediately.

“The risk to New Yorkers is real, but the defense is so simple – get vaccinated against polio,” New York City Health Commissioner Ashwin Vasan, MD, PhD, said in a statement. “Polio is entirely preventable, and its reappearance should be a call for all of us.”

Though many of those who are infected have no symptoms, about 4% will get viral meningitis “and about 1 in 200 will become paralyzed,” according to a news release.
 

Symptoms can be flu-like

Symptoms can include those similar to the flu, such as sore throat, fever, fatigue, nausea, and stomach ache. There is no cure for the disease. 

The city’s health department has given no details about where exactly polio had been found in NYC’s wastewater nor did they give dates the virus was detected.

Health authorities urged parents of children who are not yet fully vaccinated to bring them to their pediatricians.

In 1916, polio killed 6,000 people in the United States and left at least another 21,000 – most of them children – permanently disabled.

An outbreak in 1952 caused paralysis in more than 20,000 people and left many children on iron lungs. The first effective vaccine emerged just a few years later and the virus began to wane.

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

Polio virus has been discovered in New York City’s sewers, suggesting that the virus is circulating in the city, New York’s health authorities said Aug. 12.

The detection of polio in NYC is alarming but not surprising, said New York State Health Commissioner Mary Bassett, MD, MPH.

“For every one case of paralytic polio identified, hundreds more may be undetected,” Dr. Bassett said. “The best way to keep adults and children polio-free is through safe and effective immunization.”

Polio can cause permanent paralysis of limbs and even death in some cases. Before this outbreak, the last case of polio in the United States was in 2013.

The announcement came after a man in Rockland County, New York, north of the city, was stricken with polio at the end of July and paralyzed.

Now, health officials fear that the detection of polio in NYC wastewater could bring other cases of paralytic polio.

“It is not surprising, since this is something already seen with Rockland County,” Amesh Adalja, MD, senior scholar at the Johns Hopkins Center for Health Security in Baltimore, told this news organization. “This is solely the result of under-vaccination in the area. I think it’s likely that we will see a few paralytic cases but not a high number.”
 

Vaccinations declined in pandemic

Among the worries is that vaccination rates across New York City dipped during the pandemic because pediatrician visits were postponed.

In New York City, the overall rate of polio vaccination among children aged 5 years or younger is 86%. Still, in some city ZIP codes, fewer than two-thirds of children in that age group have received the full dosage, which worries health officials.

However, most adults were vaccinated against polio as children.

Across New York state, nearly 80% of people have been vaccinated, according to data from the state public health department. Those who are unvaccinated are at risk, but the polio vaccine is nearly 100% effective in people who are fully immunized.

New York health authorities are calling on those who are unvaccinated to get their shots immediately.

“The risk to New Yorkers is real, but the defense is so simple – get vaccinated against polio,” New York City Health Commissioner Ashwin Vasan, MD, PhD, said in a statement. “Polio is entirely preventable, and its reappearance should be a call for all of us.”

Though many of those who are infected have no symptoms, about 4% will get viral meningitis “and about 1 in 200 will become paralyzed,” according to a news release.
 

Symptoms can be flu-like

Symptoms can include those similar to the flu, such as sore throat, fever, fatigue, nausea, and stomach ache. There is no cure for the disease. 

The city’s health department has given no details about where exactly polio had been found in NYC’s wastewater nor did they give dates the virus was detected.

Health authorities urged parents of children who are not yet fully vaccinated to bring them to their pediatricians.

In 1916, polio killed 6,000 people in the United States and left at least another 21,000 – most of them children – permanently disabled.

An outbreak in 1952 caused paralysis in more than 20,000 people and left many children on iron lungs. The first effective vaccine emerged just a few years later and the virus began to wane.

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

Polio virus has been discovered in New York City’s sewers, suggesting that the virus is circulating in the city, New York’s health authorities said Aug. 12.

The detection of polio in NYC is alarming but not surprising, said New York State Health Commissioner Mary Bassett, MD, MPH.

“For every one case of paralytic polio identified, hundreds more may be undetected,” Dr. Bassett said. “The best way to keep adults and children polio-free is through safe and effective immunization.”

Polio can cause permanent paralysis of limbs and even death in some cases. Before this outbreak, the last case of polio in the United States was in 2013.

The announcement came after a man in Rockland County, New York, north of the city, was stricken with polio at the end of July and paralyzed.

Now, health officials fear that the detection of polio in NYC wastewater could bring other cases of paralytic polio.

“It is not surprising, since this is something already seen with Rockland County,” Amesh Adalja, MD, senior scholar at the Johns Hopkins Center for Health Security in Baltimore, told this news organization. “This is solely the result of under-vaccination in the area. I think it’s likely that we will see a few paralytic cases but not a high number.”
 

Vaccinations declined in pandemic

Among the worries is that vaccination rates across New York City dipped during the pandemic because pediatrician visits were postponed.

In New York City, the overall rate of polio vaccination among children aged 5 years or younger is 86%. Still, in some city ZIP codes, fewer than two-thirds of children in that age group have received the full dosage, which worries health officials.

However, most adults were vaccinated against polio as children.

Across New York state, nearly 80% of people have been vaccinated, according to data from the state public health department. Those who are unvaccinated are at risk, but the polio vaccine is nearly 100% effective in people who are fully immunized.

New York health authorities are calling on those who are unvaccinated to get their shots immediately.

“The risk to New Yorkers is real, but the defense is so simple – get vaccinated against polio,” New York City Health Commissioner Ashwin Vasan, MD, PhD, said in a statement. “Polio is entirely preventable, and its reappearance should be a call for all of us.”

Though many of those who are infected have no symptoms, about 4% will get viral meningitis “and about 1 in 200 will become paralyzed,” according to a news release.
 

Symptoms can be flu-like

Symptoms can include those similar to the flu, such as sore throat, fever, fatigue, nausea, and stomach ache. There is no cure for the disease. 

The city’s health department has given no details about where exactly polio had been found in NYC’s wastewater nor did they give dates the virus was detected.

Health authorities urged parents of children who are not yet fully vaccinated to bring them to their pediatricians.

In 1916, polio killed 6,000 people in the United States and left at least another 21,000 – most of them children – permanently disabled.

An outbreak in 1952 caused paralysis in more than 20,000 people and left many children on iron lungs. The first effective vaccine emerged just a few years later and the virus began to wane.

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

The connection between red meat and atherosclerotic cardiovascular disease has been well established, but newly reported findings indicate that metabolites in the gut microbiome may explain that relationship more than cholesterol and blood pressure.

“Eating more meat, especially red meat and processed meats, is associated with a higher risk of cardiovascular disease, even later in life,” co–lead study author Meng Wang, PhD, said in an interview.

The study, from a large community-based cohort of older people, included 3,931 U.S. participants aged 65 and older in the Cardiovascular Health Study (CHS). It found that gut microbiota–generated metabolites of dietary L-carnitine, including trimethylamine N-oxide (TMAO), have a role in the association between unprocessed red meat intake and incident ASCVD.

“TMAO-related metabolites produced by our gut microbes as well as blood-glucose and insulin homeostasis and systematic inflammation appeared to explain much of the association, more so than blood cholesterol or blood pressure,” added Dr. Wang, of the Friedman School of Nutrition Science and Policy at Tufts University, Boston.

Dr. Wang said this study was unique because it focused specifically on older adults; the average participant age was 72.9 years. “Older adults are at the highest risk of CVD, and for them adequate intake of protein may help to offset aging-related loss of muscle mass and strength,” she said. However, the study population was largely white (88%), so, she said, the results may not be generalizable to populations that are younger or of different nationalities and races.

The researchers performed a multivariable analysis that showed that participants who had higher intakes of unprocessed red meat, total meat, and total animal source foods (ASF) had higher hazard ratios of ASCVD risk. The study had a median follow-up of 12.5 years. It divided the study population into five quintiles based on how much unprocessed red met they consumed at baseline and analyzed dietary exposure in the differences between the midpoints of the first and fifth quintiles.

Earlier studies of meat intake and CVD risk focused mostly on saturated fat and blood cholesterol, Dr. Wang added. “But our findings suggest that other components in red meat, such as L-carnitine and heme iron, might play a more important role than saturated fat,” she said.

camij/thinkstockphotos.com

Higher intake of unprocessed red meat was linked to a 15% higher incidence of ASCVD per interquintile range (hazard ratio, 1.15; 95% confidence interval, 1.01-1.30; P = .031). Total meat intake, defined as unprocessed plus processed red meat, was tied to a 22% higher incidence of ASCVD (HR, 1.22; CI, 1.07-1.39; P = .004).

The study found no significant association between fish, poultry, or egg intake and incident ASCVD, but found total ASF intake had an 18% higher risk (HR, 1.18; CI, 1.03–1.34; P = .016).
 

Explaining the red meat–CVD connection

“The more novel part of our study is about the mediation analysis,” Dr. Wang said. “It helps explain why meat intake was associated with a higher risk of CVD. We identified several biological pathways, including the novel one through TMAO-related metabolites produced by the gut microbiome.”

Three gut microbiota–generated metabolites of L-carnitine – TMAO, gamma-butyrobetaine, and crotonobetaine – seem to partly explain the association between unprocessed red meat intake and incident ASCVD, the study reported.

The study found 3.92 excess ASCVD events per 1,000 person years associated with each interquintile range of higher unprocessed red meat intake; 10.6% of them were attributed to plasma levels of the three L-carnitine metabolites (95% CI, 1.0-114.5).

In this study, neither blood cholesterol nor blood pressure levels seemed to explain the elevated risk of ASCVD associated with meat intake, but blood glucose and insulin did, with mediation proportions of 26.1% and 11.8%, respectively.

Study strengths are its size and its general population cohort with well-measured CVD risk factors, Dr. Wang pointed out. All participants were free of clinically diagnosed CVD at enrollment, which minimized selection bias and reverse causation, she said. However, she acknowledged that the use of self-reported diet intake data, along with the largely white population, constitute limitations.

“Our study findings need to be confirmed in different populations and more research efforts are needed to better understand the health effects of some of the components in red meat, such as L-carnitine and heme iron,” Dr. Wang said.

“This study is interesting in that it doesn’t just ask the question, ‘Is eating red meat associated with coronary disease and atherosclerotic disease?’ but it tells what the mechanism is,” Robert Vogel, MD, professor at University of Colorado at Denver, Aurora, said in an interview.

The association between red meat and ASCVD is “an established science,” he said. “Where this study adds to the literature is that it suggests that elevated LDL cholesterol or blood pressure, things – especially the former – that are thought to be associated with coronary disease, may or may not be the mechanism.” He cautioned, however, “this is all associative data.”

The study “produces incremental knowledge for the association between eating red met and atherosclerosis, but it does not establish causality,” Dr. Vogel added.

Dr. Wang has no relevant disclosures. Dr. Vogel is a consultant to the Pritikin Longevity Center in Miami.

The connection between red meat and atherosclerotic cardiovascular disease has been well established, but newly reported findings indicate that metabolites in the gut microbiome may explain that relationship more than cholesterol and blood pressure.

“Eating more meat, especially red meat and processed meats, is associated with a higher risk of cardiovascular disease, even later in life,” co–lead study author Meng Wang, PhD, said in an interview.

The study, from a large community-based cohort of older people, included 3,931 U.S. participants aged 65 and older in the Cardiovascular Health Study (CHS). It found that gut microbiota–generated metabolites of dietary L-carnitine, including trimethylamine N-oxide (TMAO), have a role in the association between unprocessed red meat intake and incident ASCVD.

“TMAO-related metabolites produced by our gut microbes as well as blood-glucose and insulin homeostasis and systematic inflammation appeared to explain much of the association, more so than blood cholesterol or blood pressure,” added Dr. Wang, of the Friedman School of Nutrition Science and Policy at Tufts University, Boston.

Dr. Wang said this study was unique because it focused specifically on older adults; the average participant age was 72.9 years. “Older adults are at the highest risk of CVD, and for them adequate intake of protein may help to offset aging-related loss of muscle mass and strength,” she said. However, the study population was largely white (88%), so, she said, the results may not be generalizable to populations that are younger or of different nationalities and races.

The researchers performed a multivariable analysis that showed that participants who had higher intakes of unprocessed red meat, total meat, and total animal source foods (ASF) had higher hazard ratios of ASCVD risk. The study had a median follow-up of 12.5 years. It divided the study population into five quintiles based on how much unprocessed red met they consumed at baseline and analyzed dietary exposure in the differences between the midpoints of the first and fifth quintiles.

Earlier studies of meat intake and CVD risk focused mostly on saturated fat and blood cholesterol, Dr. Wang added. “But our findings suggest that other components in red meat, such as L-carnitine and heme iron, might play a more important role than saturated fat,” she said.

camij/thinkstockphotos.com

Higher intake of unprocessed red meat was linked to a 15% higher incidence of ASCVD per interquintile range (hazard ratio, 1.15; 95% confidence interval, 1.01-1.30; P = .031). Total meat intake, defined as unprocessed plus processed red meat, was tied to a 22% higher incidence of ASCVD (HR, 1.22; CI, 1.07-1.39; P = .004).

The study found no significant association between fish, poultry, or egg intake and incident ASCVD, but found total ASF intake had an 18% higher risk (HR, 1.18; CI, 1.03–1.34; P = .016).
 

Explaining the red meat–CVD connection

“The more novel part of our study is about the mediation analysis,” Dr. Wang said. “It helps explain why meat intake was associated with a higher risk of CVD. We identified several biological pathways, including the novel one through TMAO-related metabolites produced by the gut microbiome.”

Three gut microbiota–generated metabolites of L-carnitine – TMAO, gamma-butyrobetaine, and crotonobetaine – seem to partly explain the association between unprocessed red meat intake and incident ASCVD, the study reported.

The study found 3.92 excess ASCVD events per 1,000 person years associated with each interquintile range of higher unprocessed red meat intake; 10.6% of them were attributed to plasma levels of the three L-carnitine metabolites (95% CI, 1.0-114.5).

In this study, neither blood cholesterol nor blood pressure levels seemed to explain the elevated risk of ASCVD associated with meat intake, but blood glucose and insulin did, with mediation proportions of 26.1% and 11.8%, respectively.

Study strengths are its size and its general population cohort with well-measured CVD risk factors, Dr. Wang pointed out. All participants were free of clinically diagnosed CVD at enrollment, which minimized selection bias and reverse causation, she said. However, she acknowledged that the use of self-reported diet intake data, along with the largely white population, constitute limitations.

“Our study findings need to be confirmed in different populations and more research efforts are needed to better understand the health effects of some of the components in red meat, such as L-carnitine and heme iron,” Dr. Wang said.

“This study is interesting in that it doesn’t just ask the question, ‘Is eating red meat associated with coronary disease and atherosclerotic disease?’ but it tells what the mechanism is,” Robert Vogel, MD, professor at University of Colorado at Denver, Aurora, said in an interview.

The association between red meat and ASCVD is “an established science,” he said. “Where this study adds to the literature is that it suggests that elevated LDL cholesterol or blood pressure, things – especially the former – that are thought to be associated with coronary disease, may or may not be the mechanism.” He cautioned, however, “this is all associative data.”

The study “produces incremental knowledge for the association between eating red met and atherosclerosis, but it does not establish causality,” Dr. Vogel added.

Dr. Wang has no relevant disclosures. Dr. Vogel is a consultant to the Pritikin Longevity Center in Miami.

The connection between red meat and atherosclerotic cardiovascular disease has been well established, but newly reported findings indicate that metabolites in the gut microbiome may explain that relationship more than cholesterol and blood pressure.

“Eating more meat, especially red meat and processed meats, is associated with a higher risk of cardiovascular disease, even later in life,” co–lead study author Meng Wang, PhD, said in an interview.

The study, from a large community-based cohort of older people, included 3,931 U.S. participants aged 65 and older in the Cardiovascular Health Study (CHS). It found that gut microbiota–generated metabolites of dietary L-carnitine, including trimethylamine N-oxide (TMAO), have a role in the association between unprocessed red meat intake and incident ASCVD.

“TMAO-related metabolites produced by our gut microbes as well as blood-glucose and insulin homeostasis and systematic inflammation appeared to explain much of the association, more so than blood cholesterol or blood pressure,” added Dr. Wang, of the Friedman School of Nutrition Science and Policy at Tufts University, Boston.

Dr. Wang said this study was unique because it focused specifically on older adults; the average participant age was 72.9 years. “Older adults are at the highest risk of CVD, and for them adequate intake of protein may help to offset aging-related loss of muscle mass and strength,” she said. However, the study population was largely white (88%), so, she said, the results may not be generalizable to populations that are younger or of different nationalities and races.

The researchers performed a multivariable analysis that showed that participants who had higher intakes of unprocessed red meat, total meat, and total animal source foods (ASF) had higher hazard ratios of ASCVD risk. The study had a median follow-up of 12.5 years. It divided the study population into five quintiles based on how much unprocessed red met they consumed at baseline and analyzed dietary exposure in the differences between the midpoints of the first and fifth quintiles.

Earlier studies of meat intake and CVD risk focused mostly on saturated fat and blood cholesterol, Dr. Wang added. “But our findings suggest that other components in red meat, such as L-carnitine and heme iron, might play a more important role than saturated fat,” she said.

camij/thinkstockphotos.com

Higher intake of unprocessed red meat was linked to a 15% higher incidence of ASCVD per interquintile range (hazard ratio, 1.15; 95% confidence interval, 1.01-1.30; P = .031). Total meat intake, defined as unprocessed plus processed red meat, was tied to a 22% higher incidence of ASCVD (HR, 1.22; CI, 1.07-1.39; P = .004).

The study found no significant association between fish, poultry, or egg intake and incident ASCVD, but found total ASF intake had an 18% higher risk (HR, 1.18; CI, 1.03–1.34; P = .016).
 

Explaining the red meat–CVD connection

“The more novel part of our study is about the mediation analysis,” Dr. Wang said. “It helps explain why meat intake was associated with a higher risk of CVD. We identified several biological pathways, including the novel one through TMAO-related metabolites produced by the gut microbiome.”

Three gut microbiota–generated metabolites of L-carnitine – TMAO, gamma-butyrobetaine, and crotonobetaine – seem to partly explain the association between unprocessed red meat intake and incident ASCVD, the study reported.

The study found 3.92 excess ASCVD events per 1,000 person years associated with each interquintile range of higher unprocessed red meat intake; 10.6% of them were attributed to plasma levels of the three L-carnitine metabolites (95% CI, 1.0-114.5).

In this study, neither blood cholesterol nor blood pressure levels seemed to explain the elevated risk of ASCVD associated with meat intake, but blood glucose and insulin did, with mediation proportions of 26.1% and 11.8%, respectively.

Study strengths are its size and its general population cohort with well-measured CVD risk factors, Dr. Wang pointed out. All participants were free of clinically diagnosed CVD at enrollment, which minimized selection bias and reverse causation, she said. However, she acknowledged that the use of self-reported diet intake data, along with the largely white population, constitute limitations.

“Our study findings need to be confirmed in different populations and more research efforts are needed to better understand the health effects of some of the components in red meat, such as L-carnitine and heme iron,” Dr. Wang said.

“This study is interesting in that it doesn’t just ask the question, ‘Is eating red meat associated with coronary disease and atherosclerotic disease?’ but it tells what the mechanism is,” Robert Vogel, MD, professor at University of Colorado at Denver, Aurora, said in an interview.

The association between red meat and ASCVD is “an established science,” he said. “Where this study adds to the literature is that it suggests that elevated LDL cholesterol or blood pressure, things – especially the former – that are thought to be associated with coronary disease, may or may not be the mechanism.” He cautioned, however, “this is all associative data.”

The study “produces incremental knowledge for the association between eating red met and atherosclerosis, but it does not establish causality,” Dr. Vogel added.

Dr. Wang has no relevant disclosures. Dr. Vogel is a consultant to the Pritikin Longevity Center in Miami.

For patients with schizophrenia, long-acting injectable antipsychotics (LAIAs) are associated with a lower risk than oral antipsychotics (OAs) for disease relapse and hospitalization – and they carry no increased risk for adverse events, new research shows.

Investigators analyzed data for more than 70,000 patients with schizophrenia and found that, compared with OAs, LAIAs were associated with lower risk for hospitalizations for any cause, hospitalizations for psychiatric disorders, hospitalizations for schizophrenia, and incident suicide attempts.

courtesy University of Hong Kong

Among patients treated fully with LAIAs, there were fewer hospitalizations for somatic disorders and cardiovascular diseases and less extrapyramidal symptoms (EPS), compared with those treated fully with OAs. In addition, among those for whom treatment with LAIAs was initiated early, the reduction in these outcome events was greater in comparison with patients for whom treatment was initiated later.

The results “reinforced that LAIAs were associated with a lower risk of hospitalizations, disease relapses, and suicide attempts than OAs, and this association remained during subsequent treatment periods,” wrote the investigators, led by Esther Chan, PhD, Center for Safe Medication Practice and Research, department of pharmacology and pharmacy, University of Hong Kong.

The findings were published online in JAMA Network Open.
 

Misclassification common

“Current clinical guidelines on the use of LAIAs are derived mainly from randomized clinical trials in which strict inclusion criteria limit generalizability,” the investigators noted. In addition, most of these trials were of “relatively short duration,” so long-term observational studies are “important to establish the safety and effectiveness of LAIAs.”

Moreover, most studies have been based on Western populations, and the findings may not be generalizable to Asian populations, which have been less studied.

Previous studies were also often subject to “misclassification of exposure,” since patients treated with LAIAs alone and those treated concurrently with LAIAs and OAs were categorized together as “LAIA” users and were compared with users of OAs alone, the researchers noted.

To investigate the long-term safety and efficacy of LAIAs, they assessed data from the Clinical Data Analysis and Reporting System, an electronic health records database of the Hong Kong Hospital Authority. They identified 70,396 patients with schizophrenia (52.8% women; mean age, 44.2 years).

The investigators used a self-controlled case series design – “within-individual comparison, based on a case-only approach” – to analyze the data. This model uses incidence rate ratios derived by “comparing the rate of outcomes between exposed and unexposed or reference periods for the same individual.” In this approach, “only people with both the exposure and the outcome are eligible.”

To be included, a patient had to have received at least one OA and LAIA and had to have had at least one outcome event during the observation period of January 2004 or the date of first schizophrenia diagnosis (whichever came later) through December 2019 or death (whichever came first).

The observation period was further subdivided into four periods: a nontreatment period, a period in which OAs were used alone, a period in which LAIAs were used alone, and a period in which a combination of OAs and LAIAs were used together.

Primary outcomes included health care use and disease relapses, such as hospitalizations for psychiatric disorders, hospitalizations for schizophrenia, and incident suicide attempt. Secondary outcomes included hospitalizations for somatic disorders, hospitalizations for cardiovascular diseases, and EPS.
 

LAIAs superior

Of the total study population, 23,719 patients (33.7%) were prescribed both OAs and LAIAs (mean age, 41.7 years). Of these participants, 15.4% died during the observation period.

The mean duration of follow-up was 12.5 years. The mean duration of exposure to OAs alone was 5 years; for LAIA exposure alone, 1.4 years; and for OA plus LAIA exposure, 4.4 years.

During the observation period, almost all individuals (92.8%) had one or more ED visits, and most (88.4%) had one or more hospitalizations for any psychiatric disorder. Over three-quarters (77.5%) were hospitalized for schizophrenia, and a small percentage (6.1%) had an incident suicide attempt.

Almost all patients experienced EPS (93.5%); over half (64.9%) were hospitalized for somatic disorders; and 15.6% were hospitalized for cardiovascular diseases.

After adjustment, compared with OAs, use of LAIAs was associated with a significantly lower risk for most outcomes.

Proactive approach

Commenting on the study, Brittany Gouse, MD, assistant professor at Boston University School of Medicine and a psychiatrist in the wellness and recovery after psychosis program, Boston Medical Center, said the study “adds to the growing body of evidence supporting the longitudinal benefits” of LAIAs for patients with schizophrenia spectrum disorders.

“In particular, there may be a unique benefit to transitioning to long-acting injectable antipsychotics within the first 2 years of illness,” said Dr. Gouse, who coauthored an accompanying editorial and was not involved with the research.

She also called the study “important,” because it suggests that early initiation of LAIAs “may serve as an important tool to reduce morbidity and bridge the premature mortality gap in schizophrenia.”

Dr. Gouse emphasized the importance of prioritizing “tertiary prevention” right from the onset of psychotic illness.

“Clinicians must take a proactive approach and include long-acting antipsychotics in shared decision-making conversations with patients within the first few years of illness,” she said.

The study was funded by the Excellent Young Scientists Fund of the National Natural Science Foundation of China. Dr. Chan received grants from the National Natural Science Foundation of China during the conduct of the study; nonfinancial support from the Wellcome Trust; grants from the Research Grants Council, the Research Fund Secretariat of the Food and Health Bureau, the National Health and Medical Research Council (Australia), the narcotics division of the Security Bureau of Hong Kong SAR, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Janssen, Pfizer, Takeda, and Novartis; and personal fees from Pfizer, Novartis, and the Hong Kong SAR Hospital Authority outside the submitted work. The editorialists reported no relevant financial relationships.

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

For patients with schizophrenia, long-acting injectable antipsychotics (LAIAs) are associated with a lower risk than oral antipsychotics (OAs) for disease relapse and hospitalization – and they carry no increased risk for adverse events, new research shows.

Investigators analyzed data for more than 70,000 patients with schizophrenia and found that, compared with OAs, LAIAs were associated with lower risk for hospitalizations for any cause, hospitalizations for psychiatric disorders, hospitalizations for schizophrenia, and incident suicide attempts.

courtesy University of Hong Kong

Among patients treated fully with LAIAs, there were fewer hospitalizations for somatic disorders and cardiovascular diseases and less extrapyramidal symptoms (EPS), compared with those treated fully with OAs. In addition, among those for whom treatment with LAIAs was initiated early, the reduction in these outcome events was greater in comparison with patients for whom treatment was initiated later.

The results “reinforced that LAIAs were associated with a lower risk of hospitalizations, disease relapses, and suicide attempts than OAs, and this association remained during subsequent treatment periods,” wrote the investigators, led by Esther Chan, PhD, Center for Safe Medication Practice and Research, department of pharmacology and pharmacy, University of Hong Kong.

The findings were published online in JAMA Network Open.
 

Misclassification common

“Current clinical guidelines on the use of LAIAs are derived mainly from randomized clinical trials in which strict inclusion criteria limit generalizability,” the investigators noted. In addition, most of these trials were of “relatively short duration,” so long-term observational studies are “important to establish the safety and effectiveness of LAIAs.”

Moreover, most studies have been based on Western populations, and the findings may not be generalizable to Asian populations, which have been less studied.

Previous studies were also often subject to “misclassification of exposure,” since patients treated with LAIAs alone and those treated concurrently with LAIAs and OAs were categorized together as “LAIA” users and were compared with users of OAs alone, the researchers noted.

To investigate the long-term safety and efficacy of LAIAs, they assessed data from the Clinical Data Analysis and Reporting System, an electronic health records database of the Hong Kong Hospital Authority. They identified 70,396 patients with schizophrenia (52.8% women; mean age, 44.2 years).

The investigators used a self-controlled case series design – “within-individual comparison, based on a case-only approach” – to analyze the data. This model uses incidence rate ratios derived by “comparing the rate of outcomes between exposed and unexposed or reference periods for the same individual.” In this approach, “only people with both the exposure and the outcome are eligible.”

To be included, a patient had to have received at least one OA and LAIA and had to have had at least one outcome event during the observation period of January 2004 or the date of first schizophrenia diagnosis (whichever came later) through December 2019 or death (whichever came first).

The observation period was further subdivided into four periods: a nontreatment period, a period in which OAs were used alone, a period in which LAIAs were used alone, and a period in which a combination of OAs and LAIAs were used together.

Primary outcomes included health care use and disease relapses, such as hospitalizations for psychiatric disorders, hospitalizations for schizophrenia, and incident suicide attempt. Secondary outcomes included hospitalizations for somatic disorders, hospitalizations for cardiovascular diseases, and EPS.
 

LAIAs superior

Of the total study population, 23,719 patients (33.7%) were prescribed both OAs and LAIAs (mean age, 41.7 years). Of these participants, 15.4% died during the observation period.

The mean duration of follow-up was 12.5 years. The mean duration of exposure to OAs alone was 5 years; for LAIA exposure alone, 1.4 years; and for OA plus LAIA exposure, 4.4 years.

During the observation period, almost all individuals (92.8%) had one or more ED visits, and most (88.4%) had one or more hospitalizations for any psychiatric disorder. Over three-quarters (77.5%) were hospitalized for schizophrenia, and a small percentage (6.1%) had an incident suicide attempt.

Almost all patients experienced EPS (93.5%); over half (64.9%) were hospitalized for somatic disorders; and 15.6% were hospitalized for cardiovascular diseases.

After adjustment, compared with OAs, use of LAIAs was associated with a significantly lower risk for most outcomes.

Proactive approach

Commenting on the study, Brittany Gouse, MD, assistant professor at Boston University School of Medicine and a psychiatrist in the wellness and recovery after psychosis program, Boston Medical Center, said the study “adds to the growing body of evidence supporting the longitudinal benefits” of LAIAs for patients with schizophrenia spectrum disorders.

“In particular, there may be a unique benefit to transitioning to long-acting injectable antipsychotics within the first 2 years of illness,” said Dr. Gouse, who coauthored an accompanying editorial and was not involved with the research.

She also called the study “important,” because it suggests that early initiation of LAIAs “may serve as an important tool to reduce morbidity and bridge the premature mortality gap in schizophrenia.”

Dr. Gouse emphasized the importance of prioritizing “tertiary prevention” right from the onset of psychotic illness.

“Clinicians must take a proactive approach and include long-acting antipsychotics in shared decision-making conversations with patients within the first few years of illness,” she said.

The study was funded by the Excellent Young Scientists Fund of the National Natural Science Foundation of China. Dr. Chan received grants from the National Natural Science Foundation of China during the conduct of the study; nonfinancial support from the Wellcome Trust; grants from the Research Grants Council, the Research Fund Secretariat of the Food and Health Bureau, the National Health and Medical Research Council (Australia), the narcotics division of the Security Bureau of Hong Kong SAR, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Janssen, Pfizer, Takeda, and Novartis; and personal fees from Pfizer, Novartis, and the Hong Kong SAR Hospital Authority outside the submitted work. The editorialists reported no relevant financial relationships.

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

For patients with schizophrenia, long-acting injectable antipsychotics (LAIAs) are associated with a lower risk than oral antipsychotics (OAs) for disease relapse and hospitalization – and they carry no increased risk for adverse events, new research shows.

Investigators analyzed data for more than 70,000 patients with schizophrenia and found that, compared with OAs, LAIAs were associated with lower risk for hospitalizations for any cause, hospitalizations for psychiatric disorders, hospitalizations for schizophrenia, and incident suicide attempts.

courtesy University of Hong Kong

Among patients treated fully with LAIAs, there were fewer hospitalizations for somatic disorders and cardiovascular diseases and less extrapyramidal symptoms (EPS), compared with those treated fully with OAs. In addition, among those for whom treatment with LAIAs was initiated early, the reduction in these outcome events was greater in comparison with patients for whom treatment was initiated later.

The results “reinforced that LAIAs were associated with a lower risk of hospitalizations, disease relapses, and suicide attempts than OAs, and this association remained during subsequent treatment periods,” wrote the investigators, led by Esther Chan, PhD, Center for Safe Medication Practice and Research, department of pharmacology and pharmacy, University of Hong Kong.

The findings were published online in JAMA Network Open.
 

Misclassification common

“Current clinical guidelines on the use of LAIAs are derived mainly from randomized clinical trials in which strict inclusion criteria limit generalizability,” the investigators noted. In addition, most of these trials were of “relatively short duration,” so long-term observational studies are “important to establish the safety and effectiveness of LAIAs.”

Moreover, most studies have been based on Western populations, and the findings may not be generalizable to Asian populations, which have been less studied.

Previous studies were also often subject to “misclassification of exposure,” since patients treated with LAIAs alone and those treated concurrently with LAIAs and OAs were categorized together as “LAIA” users and were compared with users of OAs alone, the researchers noted.

To investigate the long-term safety and efficacy of LAIAs, they assessed data from the Clinical Data Analysis and Reporting System, an electronic health records database of the Hong Kong Hospital Authority. They identified 70,396 patients with schizophrenia (52.8% women; mean age, 44.2 years).

The investigators used a self-controlled case series design – “within-individual comparison, based on a case-only approach” – to analyze the data. This model uses incidence rate ratios derived by “comparing the rate of outcomes between exposed and unexposed or reference periods for the same individual.” In this approach, “only people with both the exposure and the outcome are eligible.”

To be included, a patient had to have received at least one OA and LAIA and had to have had at least one outcome event during the observation period of January 2004 or the date of first schizophrenia diagnosis (whichever came later) through December 2019 or death (whichever came first).

The observation period was further subdivided into four periods: a nontreatment period, a period in which OAs were used alone, a period in which LAIAs were used alone, and a period in which a combination of OAs and LAIAs were used together.

Primary outcomes included health care use and disease relapses, such as hospitalizations for psychiatric disorders, hospitalizations for schizophrenia, and incident suicide attempt. Secondary outcomes included hospitalizations for somatic disorders, hospitalizations for cardiovascular diseases, and EPS.
 

LAIAs superior

Of the total study population, 23,719 patients (33.7%) were prescribed both OAs and LAIAs (mean age, 41.7 years). Of these participants, 15.4% died during the observation period.

The mean duration of follow-up was 12.5 years. The mean duration of exposure to OAs alone was 5 years; for LAIA exposure alone, 1.4 years; and for OA plus LAIA exposure, 4.4 years.

During the observation period, almost all individuals (92.8%) had one or more ED visits, and most (88.4%) had one or more hospitalizations for any psychiatric disorder. Over three-quarters (77.5%) were hospitalized for schizophrenia, and a small percentage (6.1%) had an incident suicide attempt.

Almost all patients experienced EPS (93.5%); over half (64.9%) were hospitalized for somatic disorders; and 15.6% were hospitalized for cardiovascular diseases.

After adjustment, compared with OAs, use of LAIAs was associated with a significantly lower risk for most outcomes.

Proactive approach

Commenting on the study, Brittany Gouse, MD, assistant professor at Boston University School of Medicine and a psychiatrist in the wellness and recovery after psychosis program, Boston Medical Center, said the study “adds to the growing body of evidence supporting the longitudinal benefits” of LAIAs for patients with schizophrenia spectrum disorders.

“In particular, there may be a unique benefit to transitioning to long-acting injectable antipsychotics within the first 2 years of illness,” said Dr. Gouse, who coauthored an accompanying editorial and was not involved with the research.

She also called the study “important,” because it suggests that early initiation of LAIAs “may serve as an important tool to reduce morbidity and bridge the premature mortality gap in schizophrenia.”

Dr. Gouse emphasized the importance of prioritizing “tertiary prevention” right from the onset of psychotic illness.

“Clinicians must take a proactive approach and include long-acting antipsychotics in shared decision-making conversations with patients within the first few years of illness,” she said.

The study was funded by the Excellent Young Scientists Fund of the National Natural Science Foundation of China. Dr. Chan received grants from the National Natural Science Foundation of China during the conduct of the study; nonfinancial support from the Wellcome Trust; grants from the Research Grants Council, the Research Fund Secretariat of the Food and Health Bureau, the National Health and Medical Research Council (Australia), the narcotics division of the Security Bureau of Hong Kong SAR, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Janssen, Pfizer, Takeda, and Novartis; and personal fees from Pfizer, Novartis, and the Hong Kong SAR Hospital Authority outside the submitted work. The editorialists reported no relevant financial relationships.

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

New York City is closing 10 city-run sites where children younger than 5 could get the COVID-19 vaccine, with three of those sites transitioning to administer the monkeypox vaccine.

The city health department said demand for children’s COVID vaccines had been on the downswing at the clinics, which opened in late June. Meanwhile, monkeypox cases have increased, with the city declaring it a public health emergency July 30.

“We always planned to transition vaccination for very young children to providers,” the city’s health department said in a statement, according to Spectrum News NY1. “Due to the ongoing monkeypox emergency, we transitioned some of these sites to administer monkeypox vaccine.”

All the COVID vaccine sites for children will close by Aug. 14, Spectrum News NY1 said. It’s unclear if the other sites will transition to monkeypox vaccine.

No appointments for children’s COVID vaccinations had to be canceled, the city said. The plan is that children now needing the COVID vaccine can go to doctors, pharmacies, or the health department clinics.

Manhattan City Councilwoman Gale Brewer urged the health department to keep the kids’ COVID vaccine sites open through the fall.

“I strongly urge you to maintain these family-friendly sites, at least until mid-September so that children who are going to day care and school can get vaccinated,” Brewer wrote. City schools open Sept. 8

Ms. Brewer noted that the city-run sites administered the Moderna vaccines, while many doctors and neighborhood health clinics use the Pfizer vaccine. That could be a problem for a child that had not finished the Moderna regimen or for families that prefer Moderna.

According to the city health department, 2,130 people in New York City had tested positive for monkeypox as of Aug. 12.

On Friday, the city announced 9,000 additional monkeypox vaccines would be made available the morning of Aug. 13.

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

New York City is closing 10 city-run sites where children younger than 5 could get the COVID-19 vaccine, with three of those sites transitioning to administer the monkeypox vaccine.

The city health department said demand for children’s COVID vaccines had been on the downswing at the clinics, which opened in late June. Meanwhile, monkeypox cases have increased, with the city declaring it a public health emergency July 30.

“We always planned to transition vaccination for very young children to providers,” the city’s health department said in a statement, according to Spectrum News NY1. “Due to the ongoing monkeypox emergency, we transitioned some of these sites to administer monkeypox vaccine.”

All the COVID vaccine sites for children will close by Aug. 14, Spectrum News NY1 said. It’s unclear if the other sites will transition to monkeypox vaccine.

No appointments for children’s COVID vaccinations had to be canceled, the city said. The plan is that children now needing the COVID vaccine can go to doctors, pharmacies, or the health department clinics.

Manhattan City Councilwoman Gale Brewer urged the health department to keep the kids’ COVID vaccine sites open through the fall.

“I strongly urge you to maintain these family-friendly sites, at least until mid-September so that children who are going to day care and school can get vaccinated,” Brewer wrote. City schools open Sept. 8

Ms. Brewer noted that the city-run sites administered the Moderna vaccines, while many doctors and neighborhood health clinics use the Pfizer vaccine. That could be a problem for a child that had not finished the Moderna regimen or for families that prefer Moderna.

According to the city health department, 2,130 people in New York City had tested positive for monkeypox as of Aug. 12.

On Friday, the city announced 9,000 additional monkeypox vaccines would be made available the morning of Aug. 13.

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

New York City is closing 10 city-run sites where children younger than 5 could get the COVID-19 vaccine, with three of those sites transitioning to administer the monkeypox vaccine.

The city health department said demand for children’s COVID vaccines had been on the downswing at the clinics, which opened in late June. Meanwhile, monkeypox cases have increased, with the city declaring it a public health emergency July 30.

“We always planned to transition vaccination for very young children to providers,” the city’s health department said in a statement, according to Spectrum News NY1. “Due to the ongoing monkeypox emergency, we transitioned some of these sites to administer monkeypox vaccine.”

All the COVID vaccine sites for children will close by Aug. 14, Spectrum News NY1 said. It’s unclear if the other sites will transition to monkeypox vaccine.

No appointments for children’s COVID vaccinations had to be canceled, the city said. The plan is that children now needing the COVID vaccine can go to doctors, pharmacies, or the health department clinics.

Manhattan City Councilwoman Gale Brewer urged the health department to keep the kids’ COVID vaccine sites open through the fall.

“I strongly urge you to maintain these family-friendly sites, at least until mid-September so that children who are going to day care and school can get vaccinated,” Brewer wrote. City schools open Sept. 8

Ms. Brewer noted that the city-run sites administered the Moderna vaccines, while many doctors and neighborhood health clinics use the Pfizer vaccine. That could be a problem for a child that had not finished the Moderna regimen or for families that prefer Moderna.

According to the city health department, 2,130 people in New York City had tested positive for monkeypox as of Aug. 12.

On Friday, the city announced 9,000 additional monkeypox vaccines would be made available the morning of Aug. 13.

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

Only 21% of rheumatology journals showed gender-balanced editorial boards, defined as 40%-60% women members, based on data from 34 publications.

Women remain underrepresented on the editorial boards of medical journals in general, and rheumatology journals are no exception, according to Pavel V. Ovseiko, DPhil, of the University of Oxford (England) and colleagues.

“Gender representation on editorial boards matters because editorships-in-chief and editorial board memberships are prestigious roles that increase the visibility of role-holders and provide opportunities to influence research and practice through agenda setting, editorial decision making, and peer review,” the researchers wrote.

In a study published in The Lancet Rheumatology, the researchers examined the websites of 34 rheumatology publications in December 2021. The gender of the board members was estimated using a name-to-gender inference platform and checked against personal pronouns and photos used online.

Overall, six journals (15%) had female editors-in-chief or the equivalent, and 27% of the total editorial board members were women.

Occupation had a significant impact on gender representation. Gender was equally balanced (50%) for the four journals in which a publishing professional served as editor-in-chief, and women comprised 74% of the editorial board memberships held by publishing professionals.

However, women comprised only 11% of editorships and 26% of editorial board memberships held by academics or clinicians.

“Although academic rheumatology is male-dominated, academic publishing is female-dominated,” the researchers wrote.

Gender equity is important for rheumatology in part because most rheumatology patients are women, and the proportion of women in rheumatology is increasing in many countries, the researchers noted.

“Greater diversity on editorial boards is likely to have a positive effect on the quality of science through adequate consideration and reporting of sex-related and gender-related variables,” they said.

The seven journals with gender-balanced editorial boards were Acta Reumatologica Portuguesa, Arthritis & Rheumatology, Arthritis Care & Research, The Lancet Rheumatology, Lupus Science & Medicine, Nature Reviews Rheumatology, and Seminars in Arthritis and Rheumatism.

To achieve gender balance and diversity on editorial boards, the researchers offered strategies including advertising openings through open calls, establishing and monitoring gender diversity targets, and limiting editorial board appointments to fixed terms.

The study received no outside funding. The researchers had no financial conflicts to disclose, but several serve on the editorial boards of various rheumatology journals.

Only 21% of rheumatology journals showed gender-balanced editorial boards, defined as 40%-60% women members, based on data from 34 publications.

Women remain underrepresented on the editorial boards of medical journals in general, and rheumatology journals are no exception, according to Pavel V. Ovseiko, DPhil, of the University of Oxford (England) and colleagues.

“Gender representation on editorial boards matters because editorships-in-chief and editorial board memberships are prestigious roles that increase the visibility of role-holders and provide opportunities to influence research and practice through agenda setting, editorial decision making, and peer review,” the researchers wrote.

In a study published in The Lancet Rheumatology, the researchers examined the websites of 34 rheumatology publications in December 2021. The gender of the board members was estimated using a name-to-gender inference platform and checked against personal pronouns and photos used online.

Overall, six journals (15%) had female editors-in-chief or the equivalent, and 27% of the total editorial board members were women.

Occupation had a significant impact on gender representation. Gender was equally balanced (50%) for the four journals in which a publishing professional served as editor-in-chief, and women comprised 74% of the editorial board memberships held by publishing professionals.

However, women comprised only 11% of editorships and 26% of editorial board memberships held by academics or clinicians.

“Although academic rheumatology is male-dominated, academic publishing is female-dominated,” the researchers wrote.

Gender equity is important for rheumatology in part because most rheumatology patients are women, and the proportion of women in rheumatology is increasing in many countries, the researchers noted.

“Greater diversity on editorial boards is likely to have a positive effect on the quality of science through adequate consideration and reporting of sex-related and gender-related variables,” they said.

The seven journals with gender-balanced editorial boards were Acta Reumatologica Portuguesa, Arthritis & Rheumatology, Arthritis Care & Research, The Lancet Rheumatology, Lupus Science & Medicine, Nature Reviews Rheumatology, and Seminars in Arthritis and Rheumatism.

To achieve gender balance and diversity on editorial boards, the researchers offered strategies including advertising openings through open calls, establishing and monitoring gender diversity targets, and limiting editorial board appointments to fixed terms.

The study received no outside funding. The researchers had no financial conflicts to disclose, but several serve on the editorial boards of various rheumatology journals.

Only 21% of rheumatology journals showed gender-balanced editorial boards, defined as 40%-60% women members, based on data from 34 publications.

Women remain underrepresented on the editorial boards of medical journals in general, and rheumatology journals are no exception, according to Pavel V. Ovseiko, DPhil, of the University of Oxford (England) and colleagues.

“Gender representation on editorial boards matters because editorships-in-chief and editorial board memberships are prestigious roles that increase the visibility of role-holders and provide opportunities to influence research and practice through agenda setting, editorial decision making, and peer review,” the researchers wrote.

In a study published in The Lancet Rheumatology, the researchers examined the websites of 34 rheumatology publications in December 2021. The gender of the board members was estimated using a name-to-gender inference platform and checked against personal pronouns and photos used online.

Overall, six journals (15%) had female editors-in-chief or the equivalent, and 27% of the total editorial board members were women.

Occupation had a significant impact on gender representation. Gender was equally balanced (50%) for the four journals in which a publishing professional served as editor-in-chief, and women comprised 74% of the editorial board memberships held by publishing professionals.

However, women comprised only 11% of editorships and 26% of editorial board memberships held by academics or clinicians.

“Although academic rheumatology is male-dominated, academic publishing is female-dominated,” the researchers wrote.

Gender equity is important for rheumatology in part because most rheumatology patients are women, and the proportion of women in rheumatology is increasing in many countries, the researchers noted.

“Greater diversity on editorial boards is likely to have a positive effect on the quality of science through adequate consideration and reporting of sex-related and gender-related variables,” they said.

The seven journals with gender-balanced editorial boards were Acta Reumatologica Portuguesa, Arthritis & Rheumatology, Arthritis Care & Research, The Lancet Rheumatology, Lupus Science & Medicine, Nature Reviews Rheumatology, and Seminars in Arthritis and Rheumatism.

To achieve gender balance and diversity on editorial boards, the researchers offered strategies including advertising openings through open calls, establishing and monitoring gender diversity targets, and limiting editorial board appointments to fixed terms.

The study received no outside funding. The researchers had no financial conflicts to disclose, but several serve on the editorial boards of various rheumatology journals.