Feature

Doug Flora, MD, knows the value of early cancer detection because it helped him survive kidney cancer 5 years ago. But as a medical oncologist and hematologist, and the executive medical director of oncology services at St. Elizabeth Healthcare in Edgewood, Ky., he also knows that a new era of early cancer detection testing poses big challenges for his network of six hospitals and 169 specialty and primary care offices throughout Kentucky, Ohio, and Indiana.

Multicancer early detection (MCED) tests are finally a reality and could be a potential game changer because they can screen for the possibility of up to 50 different cancers in asymptomatic individuals with one blood draw. They represent one of the fastest growing segments in medical diagnostics with a projected value of $2.77 billion by 2030, according to the market research firm Grand View Research.

These tests are different from traditional liquid biopsies, which are designed to identify actionable gene mutations to help inform treatment decisions of patients already diagnosed with cancer. Instead, MCED tests work to detect fragments of circulating free DNA that have been shed by tumors and released into the bloodstream. Detecting these cancer signals could indicate that an individual has cancer well before they ever develop symptoms.

For some cancer types, particularly those commonly diagnosed at advanced stages or those without general population screening tests, MCED testing could have a significant impact.

In its new report, Grand View Research highlights nine “prominent players” active in the MCED market; of these, two have been granted breakthrough device designation by the Food and Drug Administration: OverC MCDBT by Burning Rock on Jan. 3, 2023, and Galleri by Grail in 2019. Galleri was launched in June 2021 and can be obtained with a prescription at a cost of $949.

Yet, while patients are asking for these tests and primary care physicians are prescribing them, oncologists are grappling with how to manage the first patients whose tests tell them they may have cancer.

Ordering the tests may seem straightforward, but in reality, it is not. In fact, they are so new that most health systems have no internal guidelines for physicians. Guidelines would address when the tests should be prescribed, and whether a patient should undergo more testing or be referred to an oncologist.
 

Clinical trials underway

There are currently at least 17 clinical trials underway to investigate the performance and clinical utility of MCED tests. Six of these involve Grail, including NHS-Galleri, the largest study to date of 140,000 participants in the United Kingdom where participants will be followed for 3 years with annual visits at 12 and 24 months. And, the National Cancer Institute is spearheading a clinical trial of its own, according to a search of ClinicalTrials.gov.

In September 2022, Grail presented findings from its pivotal PATHFINDER study at the annual meeting of the European Society of Medical Oncology. Researchers reported that cancer signals were detected in 1.4% (92) of 6,621 participants enrolled in the study. Of the 92, 35 people were diagnosed with 36 cancers: 19 were solid tumors (2 oropharyngeal, 5 breast, l liver, 1 intrahepatic bile duct, 2 colon/rectum, 2 prostate, 1 lung, 1 pancreas, 1 small intestine, 1 uterus, 1 ovary and 1 bone) and 17 hematologic cancers (1 plasma cell myeloma/disorders, 2 lymphoid leukemia, 2 Waldenström’s macroglobulinemia, and 12 lymphoma).

Almost half of newly diagnosed cases were cancers in stage 1 or 2. Of stage 1 cancers, three were solid tumors and four were hematologic cancers. Of stage 2 cancers, three were solid tumors and four were hematologic cancers. All other cancers were in stage 3 and 4 or were listed as recurrent or no stage. Deb Schrag, MD, MPH, chair of the department of medicine at Memorial Sloan Kettering Cancer Center in New York, who presented the results from PATHFINDER at ESMO, reported that, of all diagnosed cancers, only breast, colon/rectum, prostate, and lung have established screening protocols.

The findings were so striking that the meeting scientific co-chair, Fabrice André, MD, PhD, told ESMO the oncology field must prepare for an onslaught of new patients.

“Within the next 5 years, we will need more doctors, surgeons and nurses with more diagnostic and treatment infrastructures to care for the rising number of people who will be identified by multicancer early detection tests,” said Dr. André, who is director of research at Gustave Roussy Cancer Center, Villejuif, France, and future president of ESMO (2025-2026). “We need to involve all stakeholders in deciding new pathways of care. We need to agree who will be tested and when and where tests will be carried out, and to anticipate the changes that will happen as a result of these tests.”

But first, he urged, the need for comparative trials “across all types of cancer to find out if having an early detection test affects morbidity and mortality. We also need to know how the tests benefit patients, and how to discuss the results with them,” Dr. André said.
 

Demand may burden health systems

Dr. Flora suggested that companies like Grail are rushing their product to market without conducting long-term sizable clinical trials.

“These diagnostic companies are a billion dollar publicly traded or venture capital-funded companies that are losing millions of dollars a quarter as they’re scaling up these tests. So, there is some pressure on the sales forces ... to start moving product long before the science has met our lowest areas for entry,” Dr. Flora said. “They are aggressively marketing to a primary care audience that knows nothing about MCEDs. It’s a sales-driven development solving a problem we all believe is real, but we don’t know if it actually solves the problem.”

There are many unanswered questions, he said. Among these include whether the tests do indeed extend survival. “What they’re suggesting – that is if the blood test detects it – that we’re going to save your life. That’s not yet been proven. This is where the providers are pushing back against these industry types to say: ‘This is the wild west right now.’ It’s very irresponsible to go out there and try to sell hundreds of millions of dollars of product to doctors who have never studied genetics,” Dr. Flora said.

Grail’s chief medical officer Jeff Venstrom, MD, however, said physicians don’t need a background in genetic testing to order or interpret Galleri because it’s not a genetic test. Genetic tests look for genetic variants associated with cancer risk, which Galleri does not. MCED tests rely on genomic profiling to identify alterations in tumors.

“Maybe there’s still confusion in the market, which is common for new technologies when they’re initially launched. This is not a 23andMe test. We do not report germline mutations that have implications for cancer risk. We’re using this blood sample to test for the presence or absence of a cancer signal. The test result is very clear and simple: One area of the report says ‘yes’ or ‘no.’ It is a binary result that says if a signal is detected or not. The second provides additional information around where that signal could be coming from,” he said.

Galleri could fill a huge unmet need in cancer prevention, Dr. Venstrom said. Not only could it detect cancer at an earlier stage, but it could serve as a screening tool for cancers like pancreatic cancer in which screening is not available.

The test is not intended to replace standard of care screening, he said. The ordering provider should have a conversation with the patient about overall cancer risk. “Are you smoking? What’s your risk of obesity-associated cancers? Do you have a family history of cancer? I think this should all be in the context of a good conversation around preventative care,” he said.
 

Planning and prep in Boston

In Boston, Aparna Parikh, MD, an oncologist who specializes in gastrointestinal cancers, agreed that MCED testing has forced her team at the Mass General Cancer Center global cancer care program to think outside of the box.

“We’re a major academic center and it’s not easy [because] this is all uncharted territory,” she said. “We all recognize there are more tests coming, and they are here to stay. As a health system, we have to be ready to manage not only the tests, but patient anxieties, and all the complexities that come with it. We just don’t know yet how to best navigate.”

Although Dr. Parikh’s center has set up a working group tasked with organizing an outpatient clinic for patients with positive MCED tests, the current system is haphazard.

“Right now, it gets bounced around between people,” she explained. “Sometimes, patients are getting referred to the oncology team rather than the primary care team to try to sort out where the cancer signal is coming from, that is, if it’s not immediately obvious. No one really knows who should be the right person to own it,” Dr. Parikh said. While the test is supposed to give tissue-specific results, “it’s not perfect” and sometimes imaging and other work-ups are needed to locate the source of the signa.

“A group of four or five oncologists get looped in and then we’re trying to sort it out on a case-by-case basis, but understanding that with more and more tests coming, that kind of ad hoc approach isn’t going to be sufficient. We need a happy medium between the primary care and the disease specific oncologist, someone who can kind of help think through the diagnostic workup until they have a cancer diagnosis to get them to the right place,” Dr. Parikh said.

Dr. Venstrom said Grail is committed to providing support to clinicians in these situations. “We’re doing everything we can with our medical education forums. We have this pretty intense and extensive postpositive suite of resources,” he explained. “Some of our doctors on staff call the ordering provider within 24 hours just to clarify if there are any questions or confusion from the report. For example, if it suggests the signal is coming from the lung, we provide additional support around additional workups.”
 

Out-of-pocket test may widen disparities in care

With the exception of a few health insurance companies that have committed to covering some of the cost for the test, Galleri is an out-of-pocket expense.

Dr. Venstrom acknowledged that broad insurance coverage for the Galleri test remains a hurdle, although “we’ve secured coverage for a handful of companies of self-insured employers and forward-thinking insurers.” This includes partnerships with Point32Health, and Alignment Health, among others, he said.

There is also growing support among more than 400 cancer organizations for the Multi-Cancer Early Detection Screening Coverage Act to accelerate coverage for Medicare beneficiaries. “We are constantly trying to understand the evidence that’s needed for payors to make sure that we get the broadest access possible for this test,” he said.
 

The first positive test result

Back at St. Elizabeth Healthcare where they’ve only seen one positive MCED test result thus far, Dr. Flora is more concerned about patients giving informed consent before they even get the test. “When the reps started hammering our primary care doctors, we sent communiques throughout the system saying that we would very much like to regulate this to make sure that before our patients receive accidental harm, that they at least have a conversation with somebody who understands the test,” he explained.

All 15 patients who requested the test at the hospital were first required to discuss the implications with a genetic counselor who is part of the system. “We are really pro–cancer screening,” he said, but added his hospital is “not pumped” about the Galleri test. “We’re being very cautious about overstatements made by sales guys to our primary care doctors, so we’re letting our own precision medicine people handle it.”

There’s a similar system in place at Community Health Network, a nonprofit health system with nine hospitals and 1,300 employee providers throughout Central Indiana. Patrick McGill, MD, a primary care physician and chief analytics officer for the network says they have streamlined patients with positive tests through their high-risk oncology clinic. “They don’t go straight to a medical oncologist which I know some systems are struggling with,” he said. “They get additional testing, whether it’s imaging they might need or other lab testing. We’ve had a few lung positives, and a few leukemia positives which might go straight to medical oncology. I think we had one breast that was positive so she got additional breast imaging.”

Through its foundation, CHN will offer 2,000 tests free of charge. “We decided to take cost off the table with this funding,” Dr. McGill said. “A lot of health systems I talk to are always concerned that insurance doesn’t cover it and it’s cost prohibitive. Is it creating additional disparities because only people who can afford it can get the test?”

Dr. Schrag serves as an uncompensated advisor for Grail. Previously, while with the Dana-Farber Cancer Institute, she received research funding from Grail.

Doug Flora, MD, knows the value of early cancer detection because it helped him survive kidney cancer 5 years ago. But as a medical oncologist and hematologist, and the executive medical director of oncology services at St. Elizabeth Healthcare in Edgewood, Ky., he also knows that a new era of early cancer detection testing poses big challenges for his network of six hospitals and 169 specialty and primary care offices throughout Kentucky, Ohio, and Indiana.

Multicancer early detection (MCED) tests are finally a reality and could be a potential game changer because they can screen for the possibility of up to 50 different cancers in asymptomatic individuals with one blood draw. They represent one of the fastest growing segments in medical diagnostics with a projected value of $2.77 billion by 2030, according to the market research firm Grand View Research.

These tests are different from traditional liquid biopsies, which are designed to identify actionable gene mutations to help inform treatment decisions of patients already diagnosed with cancer. Instead, MCED tests work to detect fragments of circulating free DNA that have been shed by tumors and released into the bloodstream. Detecting these cancer signals could indicate that an individual has cancer well before they ever develop symptoms.

For some cancer types, particularly those commonly diagnosed at advanced stages or those without general population screening tests, MCED testing could have a significant impact.

In its new report, Grand View Research highlights nine “prominent players” active in the MCED market; of these, two have been granted breakthrough device designation by the Food and Drug Administration: OverC MCDBT by Burning Rock on Jan. 3, 2023, and Galleri by Grail in 2019. Galleri was launched in June 2021 and can be obtained with a prescription at a cost of $949.

Yet, while patients are asking for these tests and primary care physicians are prescribing them, oncologists are grappling with how to manage the first patients whose tests tell them they may have cancer.

Ordering the tests may seem straightforward, but in reality, it is not. In fact, they are so new that most health systems have no internal guidelines for physicians. Guidelines would address when the tests should be prescribed, and whether a patient should undergo more testing or be referred to an oncologist.
 

Clinical trials underway

There are currently at least 17 clinical trials underway to investigate the performance and clinical utility of MCED tests. Six of these involve Grail, including NHS-Galleri, the largest study to date of 140,000 participants in the United Kingdom where participants will be followed for 3 years with annual visits at 12 and 24 months. And, the National Cancer Institute is spearheading a clinical trial of its own, according to a search of ClinicalTrials.gov.

In September 2022, Grail presented findings from its pivotal PATHFINDER study at the annual meeting of the European Society of Medical Oncology. Researchers reported that cancer signals were detected in 1.4% (92) of 6,621 participants enrolled in the study. Of the 92, 35 people were diagnosed with 36 cancers: 19 were solid tumors (2 oropharyngeal, 5 breast, l liver, 1 intrahepatic bile duct, 2 colon/rectum, 2 prostate, 1 lung, 1 pancreas, 1 small intestine, 1 uterus, 1 ovary and 1 bone) and 17 hematologic cancers (1 plasma cell myeloma/disorders, 2 lymphoid leukemia, 2 Waldenström’s macroglobulinemia, and 12 lymphoma).

Almost half of newly diagnosed cases were cancers in stage 1 or 2. Of stage 1 cancers, three were solid tumors and four were hematologic cancers. Of stage 2 cancers, three were solid tumors and four were hematologic cancers. All other cancers were in stage 3 and 4 or were listed as recurrent or no stage. Deb Schrag, MD, MPH, chair of the department of medicine at Memorial Sloan Kettering Cancer Center in New York, who presented the results from PATHFINDER at ESMO, reported that, of all diagnosed cancers, only breast, colon/rectum, prostate, and lung have established screening protocols.

The findings were so striking that the meeting scientific co-chair, Fabrice André, MD, PhD, told ESMO the oncology field must prepare for an onslaught of new patients.

“Within the next 5 years, we will need more doctors, surgeons and nurses with more diagnostic and treatment infrastructures to care for the rising number of people who will be identified by multicancer early detection tests,” said Dr. André, who is director of research at Gustave Roussy Cancer Center, Villejuif, France, and future president of ESMO (2025-2026). “We need to involve all stakeholders in deciding new pathways of care. We need to agree who will be tested and when and where tests will be carried out, and to anticipate the changes that will happen as a result of these tests.”

But first, he urged, the need for comparative trials “across all types of cancer to find out if having an early detection test affects morbidity and mortality. We also need to know how the tests benefit patients, and how to discuss the results with them,” Dr. André said.
 

Demand may burden health systems

Dr. Flora suggested that companies like Grail are rushing their product to market without conducting long-term sizable clinical trials.

“These diagnostic companies are a billion dollar publicly traded or venture capital-funded companies that are losing millions of dollars a quarter as they’re scaling up these tests. So, there is some pressure on the sales forces ... to start moving product long before the science has met our lowest areas for entry,” Dr. Flora said. “They are aggressively marketing to a primary care audience that knows nothing about MCEDs. It’s a sales-driven development solving a problem we all believe is real, but we don’t know if it actually solves the problem.”

There are many unanswered questions, he said. Among these include whether the tests do indeed extend survival. “What they’re suggesting – that is if the blood test detects it – that we’re going to save your life. That’s not yet been proven. This is where the providers are pushing back against these industry types to say: ‘This is the wild west right now.’ It’s very irresponsible to go out there and try to sell hundreds of millions of dollars of product to doctors who have never studied genetics,” Dr. Flora said.

Grail’s chief medical officer Jeff Venstrom, MD, however, said physicians don’t need a background in genetic testing to order or interpret Galleri because it’s not a genetic test. Genetic tests look for genetic variants associated with cancer risk, which Galleri does not. MCED tests rely on genomic profiling to identify alterations in tumors.

“Maybe there’s still confusion in the market, which is common for new technologies when they’re initially launched. This is not a 23andMe test. We do not report germline mutations that have implications for cancer risk. We’re using this blood sample to test for the presence or absence of a cancer signal. The test result is very clear and simple: One area of the report says ‘yes’ or ‘no.’ It is a binary result that says if a signal is detected or not. The second provides additional information around where that signal could be coming from,” he said.

Galleri could fill a huge unmet need in cancer prevention, Dr. Venstrom said. Not only could it detect cancer at an earlier stage, but it could serve as a screening tool for cancers like pancreatic cancer in which screening is not available.

The test is not intended to replace standard of care screening, he said. The ordering provider should have a conversation with the patient about overall cancer risk. “Are you smoking? What’s your risk of obesity-associated cancers? Do you have a family history of cancer? I think this should all be in the context of a good conversation around preventative care,” he said.
 

Planning and prep in Boston

In Boston, Aparna Parikh, MD, an oncologist who specializes in gastrointestinal cancers, agreed that MCED testing has forced her team at the Mass General Cancer Center global cancer care program to think outside of the box.

“We’re a major academic center and it’s not easy [because] this is all uncharted territory,” she said. “We all recognize there are more tests coming, and they are here to stay. As a health system, we have to be ready to manage not only the tests, but patient anxieties, and all the complexities that come with it. We just don’t know yet how to best navigate.”

Although Dr. Parikh’s center has set up a working group tasked with organizing an outpatient clinic for patients with positive MCED tests, the current system is haphazard.

“Right now, it gets bounced around between people,” she explained. “Sometimes, patients are getting referred to the oncology team rather than the primary care team to try to sort out where the cancer signal is coming from, that is, if it’s not immediately obvious. No one really knows who should be the right person to own it,” Dr. Parikh said. While the test is supposed to give tissue-specific results, “it’s not perfect” and sometimes imaging and other work-ups are needed to locate the source of the signa.

“A group of four or five oncologists get looped in and then we’re trying to sort it out on a case-by-case basis, but understanding that with more and more tests coming, that kind of ad hoc approach isn’t going to be sufficient. We need a happy medium between the primary care and the disease specific oncologist, someone who can kind of help think through the diagnostic workup until they have a cancer diagnosis to get them to the right place,” Dr. Parikh said.

Dr. Venstrom said Grail is committed to providing support to clinicians in these situations. “We’re doing everything we can with our medical education forums. We have this pretty intense and extensive postpositive suite of resources,” he explained. “Some of our doctors on staff call the ordering provider within 24 hours just to clarify if there are any questions or confusion from the report. For example, if it suggests the signal is coming from the lung, we provide additional support around additional workups.”
 

Out-of-pocket test may widen disparities in care

With the exception of a few health insurance companies that have committed to covering some of the cost for the test, Galleri is an out-of-pocket expense.

Dr. Venstrom acknowledged that broad insurance coverage for the Galleri test remains a hurdle, although “we’ve secured coverage for a handful of companies of self-insured employers and forward-thinking insurers.” This includes partnerships with Point32Health, and Alignment Health, among others, he said.

There is also growing support among more than 400 cancer organizations for the Multi-Cancer Early Detection Screening Coverage Act to accelerate coverage for Medicare beneficiaries. “We are constantly trying to understand the evidence that’s needed for payors to make sure that we get the broadest access possible for this test,” he said.
 

The first positive test result

Back at St. Elizabeth Healthcare where they’ve only seen one positive MCED test result thus far, Dr. Flora is more concerned about patients giving informed consent before they even get the test. “When the reps started hammering our primary care doctors, we sent communiques throughout the system saying that we would very much like to regulate this to make sure that before our patients receive accidental harm, that they at least have a conversation with somebody who understands the test,” he explained.

All 15 patients who requested the test at the hospital were first required to discuss the implications with a genetic counselor who is part of the system. “We are really pro–cancer screening,” he said, but added his hospital is “not pumped” about the Galleri test. “We’re being very cautious about overstatements made by sales guys to our primary care doctors, so we’re letting our own precision medicine people handle it.”

There’s a similar system in place at Community Health Network, a nonprofit health system with nine hospitals and 1,300 employee providers throughout Central Indiana. Patrick McGill, MD, a primary care physician and chief analytics officer for the network says they have streamlined patients with positive tests through their high-risk oncology clinic. “They don’t go straight to a medical oncologist which I know some systems are struggling with,” he said. “They get additional testing, whether it’s imaging they might need or other lab testing. We’ve had a few lung positives, and a few leukemia positives which might go straight to medical oncology. I think we had one breast that was positive so she got additional breast imaging.”

Through its foundation, CHN will offer 2,000 tests free of charge. “We decided to take cost off the table with this funding,” Dr. McGill said. “A lot of health systems I talk to are always concerned that insurance doesn’t cover it and it’s cost prohibitive. Is it creating additional disparities because only people who can afford it can get the test?”

Dr. Schrag serves as an uncompensated advisor for Grail. Previously, while with the Dana-Farber Cancer Institute, she received research funding from Grail.

Doug Flora, MD, knows the value of early cancer detection because it helped him survive kidney cancer 5 years ago. But as a medical oncologist and hematologist, and the executive medical director of oncology services at St. Elizabeth Healthcare in Edgewood, Ky., he also knows that a new era of early cancer detection testing poses big challenges for his network of six hospitals and 169 specialty and primary care offices throughout Kentucky, Ohio, and Indiana.

Multicancer early detection (MCED) tests are finally a reality and could be a potential game changer because they can screen for the possibility of up to 50 different cancers in asymptomatic individuals with one blood draw. They represent one of the fastest growing segments in medical diagnostics with a projected value of $2.77 billion by 2030, according to the market research firm Grand View Research.

These tests are different from traditional liquid biopsies, which are designed to identify actionable gene mutations to help inform treatment decisions of patients already diagnosed with cancer. Instead, MCED tests work to detect fragments of circulating free DNA that have been shed by tumors and released into the bloodstream. Detecting these cancer signals could indicate that an individual has cancer well before they ever develop symptoms.

For some cancer types, particularly those commonly diagnosed at advanced stages or those without general population screening tests, MCED testing could have a significant impact.

In its new report, Grand View Research highlights nine “prominent players” active in the MCED market; of these, two have been granted breakthrough device designation by the Food and Drug Administration: OverC MCDBT by Burning Rock on Jan. 3, 2023, and Galleri by Grail in 2019. Galleri was launched in June 2021 and can be obtained with a prescription at a cost of $949.

Yet, while patients are asking for these tests and primary care physicians are prescribing them, oncologists are grappling with how to manage the first patients whose tests tell them they may have cancer.

Ordering the tests may seem straightforward, but in reality, it is not. In fact, they are so new that most health systems have no internal guidelines for physicians. Guidelines would address when the tests should be prescribed, and whether a patient should undergo more testing or be referred to an oncologist.
 

Clinical trials underway

There are currently at least 17 clinical trials underway to investigate the performance and clinical utility of MCED tests. Six of these involve Grail, including NHS-Galleri, the largest study to date of 140,000 participants in the United Kingdom where participants will be followed for 3 years with annual visits at 12 and 24 months. And, the National Cancer Institute is spearheading a clinical trial of its own, according to a search of ClinicalTrials.gov.

In September 2022, Grail presented findings from its pivotal PATHFINDER study at the annual meeting of the European Society of Medical Oncology. Researchers reported that cancer signals were detected in 1.4% (92) of 6,621 participants enrolled in the study. Of the 92, 35 people were diagnosed with 36 cancers: 19 were solid tumors (2 oropharyngeal, 5 breast, l liver, 1 intrahepatic bile duct, 2 colon/rectum, 2 prostate, 1 lung, 1 pancreas, 1 small intestine, 1 uterus, 1 ovary and 1 bone) and 17 hematologic cancers (1 plasma cell myeloma/disorders, 2 lymphoid leukemia, 2 Waldenström’s macroglobulinemia, and 12 lymphoma).

Almost half of newly diagnosed cases were cancers in stage 1 or 2. Of stage 1 cancers, three were solid tumors and four were hematologic cancers. Of stage 2 cancers, three were solid tumors and four were hematologic cancers. All other cancers were in stage 3 and 4 or were listed as recurrent or no stage. Deb Schrag, MD, MPH, chair of the department of medicine at Memorial Sloan Kettering Cancer Center in New York, who presented the results from PATHFINDER at ESMO, reported that, of all diagnosed cancers, only breast, colon/rectum, prostate, and lung have established screening protocols.

The findings were so striking that the meeting scientific co-chair, Fabrice André, MD, PhD, told ESMO the oncology field must prepare for an onslaught of new patients.

“Within the next 5 years, we will need more doctors, surgeons and nurses with more diagnostic and treatment infrastructures to care for the rising number of people who will be identified by multicancer early detection tests,” said Dr. André, who is director of research at Gustave Roussy Cancer Center, Villejuif, France, and future president of ESMO (2025-2026). “We need to involve all stakeholders in deciding new pathways of care. We need to agree who will be tested and when and where tests will be carried out, and to anticipate the changes that will happen as a result of these tests.”

But first, he urged, the need for comparative trials “across all types of cancer to find out if having an early detection test affects morbidity and mortality. We also need to know how the tests benefit patients, and how to discuss the results with them,” Dr. André said.
 

Demand may burden health systems

Dr. Flora suggested that companies like Grail are rushing their product to market without conducting long-term sizable clinical trials.

“These diagnostic companies are a billion dollar publicly traded or venture capital-funded companies that are losing millions of dollars a quarter as they’re scaling up these tests. So, there is some pressure on the sales forces ... to start moving product long before the science has met our lowest areas for entry,” Dr. Flora said. “They are aggressively marketing to a primary care audience that knows nothing about MCEDs. It’s a sales-driven development solving a problem we all believe is real, but we don’t know if it actually solves the problem.”

There are many unanswered questions, he said. Among these include whether the tests do indeed extend survival. “What they’re suggesting – that is if the blood test detects it – that we’re going to save your life. That’s not yet been proven. This is where the providers are pushing back against these industry types to say: ‘This is the wild west right now.’ It’s very irresponsible to go out there and try to sell hundreds of millions of dollars of product to doctors who have never studied genetics,” Dr. Flora said.

Grail’s chief medical officer Jeff Venstrom, MD, however, said physicians don’t need a background in genetic testing to order or interpret Galleri because it’s not a genetic test. Genetic tests look for genetic variants associated with cancer risk, which Galleri does not. MCED tests rely on genomic profiling to identify alterations in tumors.

“Maybe there’s still confusion in the market, which is common for new technologies when they’re initially launched. This is not a 23andMe test. We do not report germline mutations that have implications for cancer risk. We’re using this blood sample to test for the presence or absence of a cancer signal. The test result is very clear and simple: One area of the report says ‘yes’ or ‘no.’ It is a binary result that says if a signal is detected or not. The second provides additional information around where that signal could be coming from,” he said.

Galleri could fill a huge unmet need in cancer prevention, Dr. Venstrom said. Not only could it detect cancer at an earlier stage, but it could serve as a screening tool for cancers like pancreatic cancer in which screening is not available.

The test is not intended to replace standard of care screening, he said. The ordering provider should have a conversation with the patient about overall cancer risk. “Are you smoking? What’s your risk of obesity-associated cancers? Do you have a family history of cancer? I think this should all be in the context of a good conversation around preventative care,” he said.
 

Planning and prep in Boston

In Boston, Aparna Parikh, MD, an oncologist who specializes in gastrointestinal cancers, agreed that MCED testing has forced her team at the Mass General Cancer Center global cancer care program to think outside of the box.

“We’re a major academic center and it’s not easy [because] this is all uncharted territory,” she said. “We all recognize there are more tests coming, and they are here to stay. As a health system, we have to be ready to manage not only the tests, but patient anxieties, and all the complexities that come with it. We just don’t know yet how to best navigate.”

Although Dr. Parikh’s center has set up a working group tasked with organizing an outpatient clinic for patients with positive MCED tests, the current system is haphazard.

“Right now, it gets bounced around between people,” she explained. “Sometimes, patients are getting referred to the oncology team rather than the primary care team to try to sort out where the cancer signal is coming from, that is, if it’s not immediately obvious. No one really knows who should be the right person to own it,” Dr. Parikh said. While the test is supposed to give tissue-specific results, “it’s not perfect” and sometimes imaging and other work-ups are needed to locate the source of the signa.

“A group of four or five oncologists get looped in and then we’re trying to sort it out on a case-by-case basis, but understanding that with more and more tests coming, that kind of ad hoc approach isn’t going to be sufficient. We need a happy medium between the primary care and the disease specific oncologist, someone who can kind of help think through the diagnostic workup until they have a cancer diagnosis to get them to the right place,” Dr. Parikh said.

Dr. Venstrom said Grail is committed to providing support to clinicians in these situations. “We’re doing everything we can with our medical education forums. We have this pretty intense and extensive postpositive suite of resources,” he explained. “Some of our doctors on staff call the ordering provider within 24 hours just to clarify if there are any questions or confusion from the report. For example, if it suggests the signal is coming from the lung, we provide additional support around additional workups.”
 

Out-of-pocket test may widen disparities in care

With the exception of a few health insurance companies that have committed to covering some of the cost for the test, Galleri is an out-of-pocket expense.

Dr. Venstrom acknowledged that broad insurance coverage for the Galleri test remains a hurdle, although “we’ve secured coverage for a handful of companies of self-insured employers and forward-thinking insurers.” This includes partnerships with Point32Health, and Alignment Health, among others, he said.

There is also growing support among more than 400 cancer organizations for the Multi-Cancer Early Detection Screening Coverage Act to accelerate coverage for Medicare beneficiaries. “We are constantly trying to understand the evidence that’s needed for payors to make sure that we get the broadest access possible for this test,” he said.
 

The first positive test result

Back at St. Elizabeth Healthcare where they’ve only seen one positive MCED test result thus far, Dr. Flora is more concerned about patients giving informed consent before they even get the test. “When the reps started hammering our primary care doctors, we sent communiques throughout the system saying that we would very much like to regulate this to make sure that before our patients receive accidental harm, that they at least have a conversation with somebody who understands the test,” he explained.

All 15 patients who requested the test at the hospital were first required to discuss the implications with a genetic counselor who is part of the system. “We are really pro–cancer screening,” he said, but added his hospital is “not pumped” about the Galleri test. “We’re being very cautious about overstatements made by sales guys to our primary care doctors, so we’re letting our own precision medicine people handle it.”

There’s a similar system in place at Community Health Network, a nonprofit health system with nine hospitals and 1,300 employee providers throughout Central Indiana. Patrick McGill, MD, a primary care physician and chief analytics officer for the network says they have streamlined patients with positive tests through their high-risk oncology clinic. “They don’t go straight to a medical oncologist which I know some systems are struggling with,” he said. “They get additional testing, whether it’s imaging they might need or other lab testing. We’ve had a few lung positives, and a few leukemia positives which might go straight to medical oncology. I think we had one breast that was positive so she got additional breast imaging.”

Through its foundation, CHN will offer 2,000 tests free of charge. “We decided to take cost off the table with this funding,” Dr. McGill said. “A lot of health systems I talk to are always concerned that insurance doesn’t cover it and it’s cost prohibitive. Is it creating additional disparities because only people who can afford it can get the test?”

Dr. Schrag serves as an uncompensated advisor for Grail. Previously, while with the Dana-Farber Cancer Institute, she received research funding from Grail.

Medicare beneficiaries will pay no more than $35 a month for insulin in 2023, while ongoing work will be needed to ensure that everyone in the United States with diabetes who needs insulin can afford it.

As of Jan. 1, 2023, the new provision tucked into the Inflation Reduction Act, signed into law by President Biden in August 2022, means that beneficiaries who take insulin via pen or syringe, covered under Medicare part D (prescription drugs), fall under the $35/month co-pay cap.

On July 1, 2023, the same out-of-pocket limit will also apply to those who take insulin via pump, which falls under Medicare part B (durable medical equipment).  

The bill originally included the co-pay cap for people with private insurance as well, but that was stripped out as part of the reconciliation process and didn’t garner the necessary 60 Senate votes to keep it in prior to passage.  

However, since 2019, 22 U.S. states have passed their own co-pay caps for people with state-regulated private insurance, ranging from $25 to $100 for a 30-day supply. A few states also cap the cost of diabetes devices as well.

Moreover, federal legislation could still address co-pay caps for people with private insurance, as well as include provisions to help those without insurance to afford insulin, Niels Knutson, director of government relations for the type 1 diabetes advocacy organization JDRF, told this news organization.

“There’s a whole menu of ideas on how to address the issue of insulin affordability. Most pathways to solving this on the federal level will require 60 votes in the Senate. There is universal recognition that this is a problem. The challenge becomes: is everybody on the same page for how to fix it,” Mr. Knutson said.

JDRF is supporting the bipartisan Improving Needed Safeguards for Users of Lifesaving Insulin Now (INSULIN) Act, introduced in June 2022 by U.S. Senators Jeanne Shaheen (D-NH) and Susan Collins (R-ME), who co-chair the Senate Diabetes Caucus. The bill includes a co-pay cap and also provisions to encourage insulin manufacturers to reduce their list prices.

“The bill is unique in that it adds a pathway to reduce the cost of insulin for everybody, regardless of whether they have insurance or not ... We see the Insulin Act as being the best path forward and the most viable path to have the biggest impact for the most people,” Mr. Knutson explained.

At the same time, JDRF is also supporting a nonprofit pharmaceutical company called Civica, which plans to bring biosimilar versions of the insulin analogs glargine, lispro, and aspart to the U.S. market by 2024 at a cost of no more than $30 for a vial and $50 for a box of prefilled pens. The state of California is expected to partner with Civica as well.

“This is just another access point for insulin, especially for folks who are uninsured, that would make a big impact,” Mr. Knutson said.

Other entities that have announced intentions to bring lower-cost insulin to the United States market include the Korean firm Undbio and billionaire entrepreneur Mark Cuban, through his company Cost Plus Drugs.

“Insulin is such a clear and present crisis that we need to address,” Mr. Knutson said. “You’re seeing this problem being recognized and solutions from all different angles coming at it.”

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

Medicare beneficiaries will pay no more than $35 a month for insulin in 2023, while ongoing work will be needed to ensure that everyone in the United States with diabetes who needs insulin can afford it.

As of Jan. 1, 2023, the new provision tucked into the Inflation Reduction Act, signed into law by President Biden in August 2022, means that beneficiaries who take insulin via pen or syringe, covered under Medicare part D (prescription drugs), fall under the $35/month co-pay cap.

On July 1, 2023, the same out-of-pocket limit will also apply to those who take insulin via pump, which falls under Medicare part B (durable medical equipment).  

The bill originally included the co-pay cap for people with private insurance as well, but that was stripped out as part of the reconciliation process and didn’t garner the necessary 60 Senate votes to keep it in prior to passage.  

However, since 2019, 22 U.S. states have passed their own co-pay caps for people with state-regulated private insurance, ranging from $25 to $100 for a 30-day supply. A few states also cap the cost of diabetes devices as well.

Moreover, federal legislation could still address co-pay caps for people with private insurance, as well as include provisions to help those without insurance to afford insulin, Niels Knutson, director of government relations for the type 1 diabetes advocacy organization JDRF, told this news organization.

“There’s a whole menu of ideas on how to address the issue of insulin affordability. Most pathways to solving this on the federal level will require 60 votes in the Senate. There is universal recognition that this is a problem. The challenge becomes: is everybody on the same page for how to fix it,” Mr. Knutson said.

JDRF is supporting the bipartisan Improving Needed Safeguards for Users of Lifesaving Insulin Now (INSULIN) Act, introduced in June 2022 by U.S. Senators Jeanne Shaheen (D-NH) and Susan Collins (R-ME), who co-chair the Senate Diabetes Caucus. The bill includes a co-pay cap and also provisions to encourage insulin manufacturers to reduce their list prices.

“The bill is unique in that it adds a pathway to reduce the cost of insulin for everybody, regardless of whether they have insurance or not ... We see the Insulin Act as being the best path forward and the most viable path to have the biggest impact for the most people,” Mr. Knutson explained.

At the same time, JDRF is also supporting a nonprofit pharmaceutical company called Civica, which plans to bring biosimilar versions of the insulin analogs glargine, lispro, and aspart to the U.S. market by 2024 at a cost of no more than $30 for a vial and $50 for a box of prefilled pens. The state of California is expected to partner with Civica as well.

“This is just another access point for insulin, especially for folks who are uninsured, that would make a big impact,” Mr. Knutson said.

Other entities that have announced intentions to bring lower-cost insulin to the United States market include the Korean firm Undbio and billionaire entrepreneur Mark Cuban, through his company Cost Plus Drugs.

“Insulin is such a clear and present crisis that we need to address,” Mr. Knutson said. “You’re seeing this problem being recognized and solutions from all different angles coming at it.”

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

Medicare beneficiaries will pay no more than $35 a month for insulin in 2023, while ongoing work will be needed to ensure that everyone in the United States with diabetes who needs insulin can afford it.

As of Jan. 1, 2023, the new provision tucked into the Inflation Reduction Act, signed into law by President Biden in August 2022, means that beneficiaries who take insulin via pen or syringe, covered under Medicare part D (prescription drugs), fall under the $35/month co-pay cap.

On July 1, 2023, the same out-of-pocket limit will also apply to those who take insulin via pump, which falls under Medicare part B (durable medical equipment).  

The bill originally included the co-pay cap for people with private insurance as well, but that was stripped out as part of the reconciliation process and didn’t garner the necessary 60 Senate votes to keep it in prior to passage.  

However, since 2019, 22 U.S. states have passed their own co-pay caps for people with state-regulated private insurance, ranging from $25 to $100 for a 30-day supply. A few states also cap the cost of diabetes devices as well.

Moreover, federal legislation could still address co-pay caps for people with private insurance, as well as include provisions to help those without insurance to afford insulin, Niels Knutson, director of government relations for the type 1 diabetes advocacy organization JDRF, told this news organization.

“There’s a whole menu of ideas on how to address the issue of insulin affordability. Most pathways to solving this on the federal level will require 60 votes in the Senate. There is universal recognition that this is a problem. The challenge becomes: is everybody on the same page for how to fix it,” Mr. Knutson said.

JDRF is supporting the bipartisan Improving Needed Safeguards for Users of Lifesaving Insulin Now (INSULIN) Act, introduced in June 2022 by U.S. Senators Jeanne Shaheen (D-NH) and Susan Collins (R-ME), who co-chair the Senate Diabetes Caucus. The bill includes a co-pay cap and also provisions to encourage insulin manufacturers to reduce their list prices.

“The bill is unique in that it adds a pathway to reduce the cost of insulin for everybody, regardless of whether they have insurance or not ... We see the Insulin Act as being the best path forward and the most viable path to have the biggest impact for the most people,” Mr. Knutson explained.

At the same time, JDRF is also supporting a nonprofit pharmaceutical company called Civica, which plans to bring biosimilar versions of the insulin analogs glargine, lispro, and aspart to the U.S. market by 2024 at a cost of no more than $30 for a vial and $50 for a box of prefilled pens. The state of California is expected to partner with Civica as well.

“This is just another access point for insulin, especially for folks who are uninsured, that would make a big impact,” Mr. Knutson said.

Other entities that have announced intentions to bring lower-cost insulin to the United States market include the Korean firm Undbio and billionaire entrepreneur Mark Cuban, through his company Cost Plus Drugs.

“Insulin is such a clear and present crisis that we need to address,” Mr. Knutson said. “You’re seeing this problem being recognized and solutions from all different angles coming at it.”

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

More than a quarter of cardiologists in an international survey reported experiencing mental health conditions ranging from anxiety or anger issues to major depression or other psychiatric disorders.  

Such conditions varied in prevalence by cardiology subspecialty and years in the field, were more common in women than in men, and were closely linked to enduring hostile work environments and other strains of professional life.

The survey, conducted only months before the COVID-19 pandemic and with its share of limitations, still paints a picture that’s not pretty.

For example, mental health concerns were reported by about 42% of respondents who cited a hostile work environment, defined as workplace experience of discrimination based on age, sex, religion, race or ethnicity, or emotional or sexual harassment. Conversely, the prevalence of these concerns reached only 17% among those without such workplace conditions.

The study shows substantial overlap between cardiologists reporting hostility at work and those with mental health concerns, “and that was a significant finding,” Garima Sharma, MD, Johns Hopkins University, Baltimore, said in an interview.

Still, only 31% of male and 42% of female cardiologists (P < .001) reporting mental health concerns also said they had sought professional help either within or outside their own institutions.

That means “there is a lot of silent suffering” in the field, said Dr. Sharma, who is lead author on the study, published in the Journal of the American College of Cardiology.
 

Bringing back the conversation

The survey findings, she added, point to at least two potential ways the cardiology community can strive to diminish what may be a major underlying cause of the mental health concerns and their consequences.

“If you work towards reducing hostility at work and making mental health a priority for your workforce, then those experiencing these types of egregious conditions based on age, gender, race, ethnicity, or sexual orientation are less likely to be harmed.”

Mental health concerns among cardiologists are seldom openly discussed, so the current study can be “a way to bring them back into the conversation,” Dr. Sharma said. Clinician mental health “is extremely important because it directly impacts patient care and productivity.”

The survey’s reported mental health conditions “are an issue across the board in medicine, and amongst our medical students as well,” senior author Laxmi S. Mehta, MD, professor of internal medicine at Ohio State University, Columbus, said in an interview. The current study provides new details about their prevalence and predictors in cardiology and, she hopes, may improve the field’s awareness of and efforts to address the problem.

“We need to support those who have underlying mental health conditions, as well as improve the work environment to reduce contributory factors to mental illnesses. And we also need to work on reducing the stigma associated with seeking treatment and on reducing the barriers to receiving treatment,” said Dr. Mehta, who chairs the Workgroup on Clinician Well-Being of the ACC, which conducted the survey in 2019.
 

A global perspective

Cardiologists in Africa, the Americas, Asia, Europe, the Middle East, and Oceania – 5,890 in all – responded to mental health questions on the survey, which was novel for its global reach and insights across continents and cultures.

Respondents in South America and Central America reported the highest prevalences of mental health concerns, outliers at about 39% and 33%, respectively. Rates for most other geographic regions ranged narrowly from about 20% to 26%, the lowest reported in Asia and the Middle East.

Dr. Sharma acknowledged that the countries probably varied widely in social and cultural factors likely to influence survey responses, such as interpretation of the questionnaire’s mental health terminology or the degree to which the disorders are stigmatized.

“I think it’s hard to say how people may or may not respond culturally to a certain word or metric,” she said. But on the survey results, “whether you’re practicing in rural America, in rural India, or in the United Arab Emirates, Oceania, or Eastern Europe, there is a level of consistency, across the board, in what people are recognizing as mental health conditions.”
 

Junior vs. senior physicians

The global perspective “is a nice positive of the study, and the high rates in Central America and South America I think were something the field was not aware of and are an important contribution,” Srijan Sen, MD, PhD, said in an interview.

The psychological toll of hostile work environments is an issue throughout medicine, “but it seems greater in certain specialties, and cardiology may be one where it’s more of a problem,” observed Dr. Sen, who studies physician mental health at the University of Michigan, Ann Arbor, and wasn’t associated with the survey.

Mental health concerns in the survey were significantly more common among women than men (33.7% vs 26.3%), and for younger cardiologists, compared with older cardiologists (32.2% for those < 40 vs. 22.1% and 16.8% for those 55-69 and 70 or older, respectively).

Those findings seem to make sense, Dr. Sen observed. “Generally, cardiology and medicine broadly are hierarchical, so being more junior can be stressful.” And if there’s more hostility in the workplace, “it might fall on junior people.”

In other studies, moreover, “a high level of work-family conflict has been a real driver of depression and burnout, and that likely is affecting younger physicians, particularly young women physicians,” who may have smaller children and a greater burden of childcare than their seniors.

He pointed to the survey’s low response rate as an important limitation of the study. Of the 71,022 cardiologists invited to participate, only 5,890 (8.3%) responded and answered the queries on mental health.

With a response rate that low, a survey “can be biased in ways that we can’t predict,” Dr. Sen noted. Also, anyone concerned about the toxicity of their own workplace might be “more likely to respond to the survey than if they worked in a more pleasant place. That would provide a skewed sense of the overall experience of cardiologists.”

Those issues might not be a concern with the current survey, however, “because the results are consistent with other studies with higher response rates.”
 

‘Sobering report’

An accompanying editorial said Dr. Sharm and colleagues have provided “a sobering report on the global prevalence and potential contributors to mental health concerns” in the surveyed population.

Based on its lessons, Andrew J. Sauer, MD, Saint Luke’s Mid America Heart Institute, Kansas City, Mo., proposed several potential “interventions” the field could enact.

It could “selectively promote leaders who strive to mitigate implicit bias, discrimination, and harassment while advancing diversity, equity, and inclusion within the broad ranks of cardiologists.”

Also, he continued, “we must eliminate the stigmatization of mental illness among physicians. We need to handle mental health concerns with compassion and without blaming, like how we strive to treat our veterans who suffer from posttraumatic stress disorder.”

Lastly, Dr. Sauer wrote, “mentorship programs should be formalized to assist the cardiologist in transition zones from early to mid-career, with particular attention to women and those experiencing a simultaneously increased load of family burdens that compound existing workplace contributors to burnout and psychological distress.”
 

Years in practice

Of the cardiologists who responded to the survey’s mental health questions, 28% reported they have experienced mental health issues that could include alcohol/drug use disorder, suicidal tendencies, psychological distress (including anxiety, irritability, or anger), “other psychiatric disorders” (such as panic disorder, posttraumatic stress, or eating disorders) or major psychiatric disorders such as major depression, bipolar disorder, or schizophrenia.

Cardiologists with 5-10 years of practice post-training were more likely than cardiologists practicing for at least 20 years to have mental health concerns (31.9% vs. 22.6%, P < .001).

Mental health concerns were cited by 42% of respondents who cited “any type of discrimination” based on age, sex, race or ethnicity, or sexual orientation, the report noted.

Among those reporting any mental health concern, 2.7% considered suicide within the past year and 2.9% considered suicide more than 12 months previously. Women were more likely than men to consider suicide within the past year (3.8% vs. 2.3%) but were also more likely to seek help (42.3% vs. 31.1%; P < .001 for both differences), the authors wrote.

In multivariate analysis, predictors of mental health concerns included emotional harassment, 2.81 (odds ratio, 2.81; 95% confidence interval, 2.46-3.20), any discrimination (OR, 1.85; 95% CI, 1.61-2.12), being divorced (OR, 1.73; 95% CI, 1.26-2.36, age less than 55 years (OR, 1.43; 95% CI, 1.24-1.66), and being mid-career versus late (OR, 1.36; 95% CI, 1.14-1.62).

Because the survey was conducted from September to October 2019, before the pandemic’s traumatic effects unfolded on health care nearly everywhere, “I think there needs to be a follow-up at some point when everything has leveled out,” Dr. Sharma said. The current study is “a baseline, and not a healthy baseline,” for the field’s state of mental health that has likely grown worse during the pandemic.

But even without such a follow-up, the current study “is actionable enough that it forces us to do something about it right now.”

Dr. Sharma, Dr. Mehta, their coauthors, Dr. Sen, and Dr. Sauer reported no relevant disclosures.

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

More than a quarter of cardiologists in an international survey reported experiencing mental health conditions ranging from anxiety or anger issues to major depression or other psychiatric disorders.  

Such conditions varied in prevalence by cardiology subspecialty and years in the field, were more common in women than in men, and were closely linked to enduring hostile work environments and other strains of professional life.

The survey, conducted only months before the COVID-19 pandemic and with its share of limitations, still paints a picture that’s not pretty.

For example, mental health concerns were reported by about 42% of respondents who cited a hostile work environment, defined as workplace experience of discrimination based on age, sex, religion, race or ethnicity, or emotional or sexual harassment. Conversely, the prevalence of these concerns reached only 17% among those without such workplace conditions.

The study shows substantial overlap between cardiologists reporting hostility at work and those with mental health concerns, “and that was a significant finding,” Garima Sharma, MD, Johns Hopkins University, Baltimore, said in an interview.

Still, only 31% of male and 42% of female cardiologists (P < .001) reporting mental health concerns also said they had sought professional help either within or outside their own institutions.

That means “there is a lot of silent suffering” in the field, said Dr. Sharma, who is lead author on the study, published in the Journal of the American College of Cardiology.
 

Bringing back the conversation

The survey findings, she added, point to at least two potential ways the cardiology community can strive to diminish what may be a major underlying cause of the mental health concerns and their consequences.

“If you work towards reducing hostility at work and making mental health a priority for your workforce, then those experiencing these types of egregious conditions based on age, gender, race, ethnicity, or sexual orientation are less likely to be harmed.”

Mental health concerns among cardiologists are seldom openly discussed, so the current study can be “a way to bring them back into the conversation,” Dr. Sharma said. Clinician mental health “is extremely important because it directly impacts patient care and productivity.”

The survey’s reported mental health conditions “are an issue across the board in medicine, and amongst our medical students as well,” senior author Laxmi S. Mehta, MD, professor of internal medicine at Ohio State University, Columbus, said in an interview. The current study provides new details about their prevalence and predictors in cardiology and, she hopes, may improve the field’s awareness of and efforts to address the problem.

“We need to support those who have underlying mental health conditions, as well as improve the work environment to reduce contributory factors to mental illnesses. And we also need to work on reducing the stigma associated with seeking treatment and on reducing the barriers to receiving treatment,” said Dr. Mehta, who chairs the Workgroup on Clinician Well-Being of the ACC, which conducted the survey in 2019.
 

A global perspective

Cardiologists in Africa, the Americas, Asia, Europe, the Middle East, and Oceania – 5,890 in all – responded to mental health questions on the survey, which was novel for its global reach and insights across continents and cultures.

Respondents in South America and Central America reported the highest prevalences of mental health concerns, outliers at about 39% and 33%, respectively. Rates for most other geographic regions ranged narrowly from about 20% to 26%, the lowest reported in Asia and the Middle East.

Dr. Sharma acknowledged that the countries probably varied widely in social and cultural factors likely to influence survey responses, such as interpretation of the questionnaire’s mental health terminology or the degree to which the disorders are stigmatized.

“I think it’s hard to say how people may or may not respond culturally to a certain word or metric,” she said. But on the survey results, “whether you’re practicing in rural America, in rural India, or in the United Arab Emirates, Oceania, or Eastern Europe, there is a level of consistency, across the board, in what people are recognizing as mental health conditions.”
 

Junior vs. senior physicians

The global perspective “is a nice positive of the study, and the high rates in Central America and South America I think were something the field was not aware of and are an important contribution,” Srijan Sen, MD, PhD, said in an interview.

The psychological toll of hostile work environments is an issue throughout medicine, “but it seems greater in certain specialties, and cardiology may be one where it’s more of a problem,” observed Dr. Sen, who studies physician mental health at the University of Michigan, Ann Arbor, and wasn’t associated with the survey.

Mental health concerns in the survey were significantly more common among women than men (33.7% vs 26.3%), and for younger cardiologists, compared with older cardiologists (32.2% for those < 40 vs. 22.1% and 16.8% for those 55-69 and 70 or older, respectively).

Those findings seem to make sense, Dr. Sen observed. “Generally, cardiology and medicine broadly are hierarchical, so being more junior can be stressful.” And if there’s more hostility in the workplace, “it might fall on junior people.”

In other studies, moreover, “a high level of work-family conflict has been a real driver of depression and burnout, and that likely is affecting younger physicians, particularly young women physicians,” who may have smaller children and a greater burden of childcare than their seniors.

He pointed to the survey’s low response rate as an important limitation of the study. Of the 71,022 cardiologists invited to participate, only 5,890 (8.3%) responded and answered the queries on mental health.

With a response rate that low, a survey “can be biased in ways that we can’t predict,” Dr. Sen noted. Also, anyone concerned about the toxicity of their own workplace might be “more likely to respond to the survey than if they worked in a more pleasant place. That would provide a skewed sense of the overall experience of cardiologists.”

Those issues might not be a concern with the current survey, however, “because the results are consistent with other studies with higher response rates.”
 

‘Sobering report’

An accompanying editorial said Dr. Sharm and colleagues have provided “a sobering report on the global prevalence and potential contributors to mental health concerns” in the surveyed population.

Based on its lessons, Andrew J. Sauer, MD, Saint Luke’s Mid America Heart Institute, Kansas City, Mo., proposed several potential “interventions” the field could enact.

It could “selectively promote leaders who strive to mitigate implicit bias, discrimination, and harassment while advancing diversity, equity, and inclusion within the broad ranks of cardiologists.”

Also, he continued, “we must eliminate the stigmatization of mental illness among physicians. We need to handle mental health concerns with compassion and without blaming, like how we strive to treat our veterans who suffer from posttraumatic stress disorder.”

Lastly, Dr. Sauer wrote, “mentorship programs should be formalized to assist the cardiologist in transition zones from early to mid-career, with particular attention to women and those experiencing a simultaneously increased load of family burdens that compound existing workplace contributors to burnout and psychological distress.”
 

Years in practice

Of the cardiologists who responded to the survey’s mental health questions, 28% reported they have experienced mental health issues that could include alcohol/drug use disorder, suicidal tendencies, psychological distress (including anxiety, irritability, or anger), “other psychiatric disorders” (such as panic disorder, posttraumatic stress, or eating disorders) or major psychiatric disorders such as major depression, bipolar disorder, or schizophrenia.

Cardiologists with 5-10 years of practice post-training were more likely than cardiologists practicing for at least 20 years to have mental health concerns (31.9% vs. 22.6%, P < .001).

Mental health concerns were cited by 42% of respondents who cited “any type of discrimination” based on age, sex, race or ethnicity, or sexual orientation, the report noted.

Among those reporting any mental health concern, 2.7% considered suicide within the past year and 2.9% considered suicide more than 12 months previously. Women were more likely than men to consider suicide within the past year (3.8% vs. 2.3%) but were also more likely to seek help (42.3% vs. 31.1%; P < .001 for both differences), the authors wrote.

In multivariate analysis, predictors of mental health concerns included emotional harassment, 2.81 (odds ratio, 2.81; 95% confidence interval, 2.46-3.20), any discrimination (OR, 1.85; 95% CI, 1.61-2.12), being divorced (OR, 1.73; 95% CI, 1.26-2.36, age less than 55 years (OR, 1.43; 95% CI, 1.24-1.66), and being mid-career versus late (OR, 1.36; 95% CI, 1.14-1.62).

Because the survey was conducted from September to October 2019, before the pandemic’s traumatic effects unfolded on health care nearly everywhere, “I think there needs to be a follow-up at some point when everything has leveled out,” Dr. Sharma said. The current study is “a baseline, and not a healthy baseline,” for the field’s state of mental health that has likely grown worse during the pandemic.

But even without such a follow-up, the current study “is actionable enough that it forces us to do something about it right now.”

Dr. Sharma, Dr. Mehta, their coauthors, Dr. Sen, and Dr. Sauer reported no relevant disclosures.

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

More than a quarter of cardiologists in an international survey reported experiencing mental health conditions ranging from anxiety or anger issues to major depression or other psychiatric disorders.  

Such conditions varied in prevalence by cardiology subspecialty and years in the field, were more common in women than in men, and were closely linked to enduring hostile work environments and other strains of professional life.

The survey, conducted only months before the COVID-19 pandemic and with its share of limitations, still paints a picture that’s not pretty.

For example, mental health concerns were reported by about 42% of respondents who cited a hostile work environment, defined as workplace experience of discrimination based on age, sex, religion, race or ethnicity, or emotional or sexual harassment. Conversely, the prevalence of these concerns reached only 17% among those without such workplace conditions.

The study shows substantial overlap between cardiologists reporting hostility at work and those with mental health concerns, “and that was a significant finding,” Garima Sharma, MD, Johns Hopkins University, Baltimore, said in an interview.

Still, only 31% of male and 42% of female cardiologists (P < .001) reporting mental health concerns also said they had sought professional help either within or outside their own institutions.

That means “there is a lot of silent suffering” in the field, said Dr. Sharma, who is lead author on the study, published in the Journal of the American College of Cardiology.
 

Bringing back the conversation

The survey findings, she added, point to at least two potential ways the cardiology community can strive to diminish what may be a major underlying cause of the mental health concerns and their consequences.

“If you work towards reducing hostility at work and making mental health a priority for your workforce, then those experiencing these types of egregious conditions based on age, gender, race, ethnicity, or sexual orientation are less likely to be harmed.”

Mental health concerns among cardiologists are seldom openly discussed, so the current study can be “a way to bring them back into the conversation,” Dr. Sharma said. Clinician mental health “is extremely important because it directly impacts patient care and productivity.”

The survey’s reported mental health conditions “are an issue across the board in medicine, and amongst our medical students as well,” senior author Laxmi S. Mehta, MD, professor of internal medicine at Ohio State University, Columbus, said in an interview. The current study provides new details about their prevalence and predictors in cardiology and, she hopes, may improve the field’s awareness of and efforts to address the problem.

“We need to support those who have underlying mental health conditions, as well as improve the work environment to reduce contributory factors to mental illnesses. And we also need to work on reducing the stigma associated with seeking treatment and on reducing the barriers to receiving treatment,” said Dr. Mehta, who chairs the Workgroup on Clinician Well-Being of the ACC, which conducted the survey in 2019.
 

A global perspective

Cardiologists in Africa, the Americas, Asia, Europe, the Middle East, and Oceania – 5,890 in all – responded to mental health questions on the survey, which was novel for its global reach and insights across continents and cultures.

Respondents in South America and Central America reported the highest prevalences of mental health concerns, outliers at about 39% and 33%, respectively. Rates for most other geographic regions ranged narrowly from about 20% to 26%, the lowest reported in Asia and the Middle East.

Dr. Sharma acknowledged that the countries probably varied widely in social and cultural factors likely to influence survey responses, such as interpretation of the questionnaire’s mental health terminology or the degree to which the disorders are stigmatized.

“I think it’s hard to say how people may or may not respond culturally to a certain word or metric,” she said. But on the survey results, “whether you’re practicing in rural America, in rural India, or in the United Arab Emirates, Oceania, or Eastern Europe, there is a level of consistency, across the board, in what people are recognizing as mental health conditions.”
 

Junior vs. senior physicians

The global perspective “is a nice positive of the study, and the high rates in Central America and South America I think were something the field was not aware of and are an important contribution,” Srijan Sen, MD, PhD, said in an interview.

The psychological toll of hostile work environments is an issue throughout medicine, “but it seems greater in certain specialties, and cardiology may be one where it’s more of a problem,” observed Dr. Sen, who studies physician mental health at the University of Michigan, Ann Arbor, and wasn’t associated with the survey.

Mental health concerns in the survey were significantly more common among women than men (33.7% vs 26.3%), and for younger cardiologists, compared with older cardiologists (32.2% for those < 40 vs. 22.1% and 16.8% for those 55-69 and 70 or older, respectively).

Those findings seem to make sense, Dr. Sen observed. “Generally, cardiology and medicine broadly are hierarchical, so being more junior can be stressful.” And if there’s more hostility in the workplace, “it might fall on junior people.”

In other studies, moreover, “a high level of work-family conflict has been a real driver of depression and burnout, and that likely is affecting younger physicians, particularly young women physicians,” who may have smaller children and a greater burden of childcare than their seniors.

He pointed to the survey’s low response rate as an important limitation of the study. Of the 71,022 cardiologists invited to participate, only 5,890 (8.3%) responded and answered the queries on mental health.

With a response rate that low, a survey “can be biased in ways that we can’t predict,” Dr. Sen noted. Also, anyone concerned about the toxicity of their own workplace might be “more likely to respond to the survey than if they worked in a more pleasant place. That would provide a skewed sense of the overall experience of cardiologists.”

Those issues might not be a concern with the current survey, however, “because the results are consistent with other studies with higher response rates.”
 

‘Sobering report’

An accompanying editorial said Dr. Sharm and colleagues have provided “a sobering report on the global prevalence and potential contributors to mental health concerns” in the surveyed population.

Based on its lessons, Andrew J. Sauer, MD, Saint Luke’s Mid America Heart Institute, Kansas City, Mo., proposed several potential “interventions” the field could enact.

It could “selectively promote leaders who strive to mitigate implicit bias, discrimination, and harassment while advancing diversity, equity, and inclusion within the broad ranks of cardiologists.”

Also, he continued, “we must eliminate the stigmatization of mental illness among physicians. We need to handle mental health concerns with compassion and without blaming, like how we strive to treat our veterans who suffer from posttraumatic stress disorder.”

Lastly, Dr. Sauer wrote, “mentorship programs should be formalized to assist the cardiologist in transition zones from early to mid-career, with particular attention to women and those experiencing a simultaneously increased load of family burdens that compound existing workplace contributors to burnout and psychological distress.”
 

Years in practice

Of the cardiologists who responded to the survey’s mental health questions, 28% reported they have experienced mental health issues that could include alcohol/drug use disorder, suicidal tendencies, psychological distress (including anxiety, irritability, or anger), “other psychiatric disorders” (such as panic disorder, posttraumatic stress, or eating disorders) or major psychiatric disorders such as major depression, bipolar disorder, or schizophrenia.

Cardiologists with 5-10 years of practice post-training were more likely than cardiologists practicing for at least 20 years to have mental health concerns (31.9% vs. 22.6%, P < .001).

Mental health concerns were cited by 42% of respondents who cited “any type of discrimination” based on age, sex, race or ethnicity, or sexual orientation, the report noted.

Among those reporting any mental health concern, 2.7% considered suicide within the past year and 2.9% considered suicide more than 12 months previously. Women were more likely than men to consider suicide within the past year (3.8% vs. 2.3%) but were also more likely to seek help (42.3% vs. 31.1%; P < .001 for both differences), the authors wrote.

In multivariate analysis, predictors of mental health concerns included emotional harassment, 2.81 (odds ratio, 2.81; 95% confidence interval, 2.46-3.20), any discrimination (OR, 1.85; 95% CI, 1.61-2.12), being divorced (OR, 1.73; 95% CI, 1.26-2.36, age less than 55 years (OR, 1.43; 95% CI, 1.24-1.66), and being mid-career versus late (OR, 1.36; 95% CI, 1.14-1.62).

Because the survey was conducted from September to October 2019, before the pandemic’s traumatic effects unfolded on health care nearly everywhere, “I think there needs to be a follow-up at some point when everything has leveled out,” Dr. Sharma said. The current study is “a baseline, and not a healthy baseline,” for the field’s state of mental health that has likely grown worse during the pandemic.

But even without such a follow-up, the current study “is actionable enough that it forces us to do something about it right now.”

Dr. Sharma, Dr. Mehta, their coauthors, Dr. Sen, and Dr. Sauer reported no relevant disclosures.

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

Could gut health be behind a person’s motivation – or lack thereof – to exercise?

Researchers at the University of Pennsylvania, Philadelphia recently explored this topic when they wanted to find out why some lab mice seem to love their exercise wheel, while others mostly ignore it.

To start, the researchers used a machine-learning algorithm to look for biological traits that could explain the differences in activity levels among mice. And what they found surprised them: Genetics seemed to have little to do with it, but differences in gut bacteria appeared to matter more. A handful of studies backed that up: Thriving gut microbiomes have been linked with optimal muscle function in mice.

Sure enough, when the researchers dosed mice with broad-spectrum antibiotics, killing off their gut bacteria, the distance the rodents were able to run dropped by half. But off the antibiotics, the mice mostly regained their previous performance levels.

The findings, published in the journal Nature, suggest that the gut microbiome may help regulate the desire to exercise. 

If confirmed in humans, this hypothesis could help explain why so many Americans fail to get the recommended amount of physical activity. Some may blame lack of time, energy, or interest. But perhaps the reason could come down to the trillions of microbes living in their gut. 

This line of research could also lead to microbiome-based ways to get sedentary people off the couch or optimize athletic performance.  

But how could one’s microbiome impact the motivation to move? To find the answer, the researchers zeroed in on the brain. 
 

The gut-brain connection

After treating the mice with antibiotics, the researchers sequenced RNA in the rodents’ striatum (the part of the brain responsible for motivation). They found reduced gene expression in the cells’ dopamine receptors – which release the neurochemical dopamine, making one feel like they’ve accomplished something good. In other words: Mice treated with antibiotics were getting less of a dopamine hit after their run. 

“Only when we started focusing on the brain did we understand that the microbiome’s effect on exercise capacity was mediated by the central and peripheral nervous systems,” said study author Christoph Thaiss, PhD, a microbiologist at the University of Pennsylvania. “This realization completely changed the trajectory of the project.”

To find out how, exactly, bacteria in the colon were signaling the brain, the researchers performed a series of experiments over several years. They identified two types of bacteria, Eubacterium rectale and Coprococcus eutactus. These strains produce compounds called fatty acid amides that interact with endocannabinoid receptors in the gut. 

Those endocannabinoid receptors signal the brain to cut back its production of monoamine oxidase, the compound that breaks down dopamine. With less of this dopamine-clearing compound in the brain, more dopamine could build up after a long run, making the mice feel good and eager to hit the exercise wheel again soon. 

This gut-brain pathway “may have evolved to couple the initiation of prolonged physical activity to the nutritional status of the gastrointestinal tract,” Dr. Thaiss said. Gut bacteria monitor what’s in your colon and tell your brain whether you have enough food to fuel a workout. 

The colon, or gut, hosts trillions of microbes with potentially hundreds of different bacteria strains. These strains are determined by the food we eat and the environment we occupy.

“The genetic impact on the microbiome is rather minor,” Dr. Thaiss said, “but lifestyle factors strongly impact the composition of the gut microbiome.”

He hopes to develop nutritional interventions to encourage the growth of the motivating types of bacteria, the kind that make a person want to go for a 5-mile run.
 

What’s next?  

Moving forward,  the researchers need to find out whether the gut affects motivation in humans, too. To do that, they’re analyzing the gut microbiomes of people with varying levels of exercise motivation. 

“With enough samples, we could potentially correlate species of microbiota that exist in exercise-motivated individuals,” said study coauthor Nicholas Betley, PhD, a biologist at the University of Pennsylvania. 

Variations in the gut microbiome could help explain the “runner’s high” that some people have in a long-distance race. The research could also help promote weight training or sports participation. 

“Imagine if a sports team could optimally motivate the athletes on the team to exercise,” said Dr. Betley. The lab is investigating the microbiome’s impact on high-intensity interval training.

Signals from the gut to the brain could be affecting body processes in other ways too, the researchers speculated. 

“There are so many possibilities for how these signals may change physiology and impact health,” Dr. Betley said. “A new set of studies may well establish a whole new branch of exercise physiology.”

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

Could gut health be behind a person’s motivation – or lack thereof – to exercise?

Researchers at the University of Pennsylvania, Philadelphia recently explored this topic when they wanted to find out why some lab mice seem to love their exercise wheel, while others mostly ignore it.

To start, the researchers used a machine-learning algorithm to look for biological traits that could explain the differences in activity levels among mice. And what they found surprised them: Genetics seemed to have little to do with it, but differences in gut bacteria appeared to matter more. A handful of studies backed that up: Thriving gut microbiomes have been linked with optimal muscle function in mice.

Sure enough, when the researchers dosed mice with broad-spectrum antibiotics, killing off their gut bacteria, the distance the rodents were able to run dropped by half. But off the antibiotics, the mice mostly regained their previous performance levels.

The findings, published in the journal Nature, suggest that the gut microbiome may help regulate the desire to exercise. 

If confirmed in humans, this hypothesis could help explain why so many Americans fail to get the recommended amount of physical activity. Some may blame lack of time, energy, or interest. But perhaps the reason could come down to the trillions of microbes living in their gut. 

This line of research could also lead to microbiome-based ways to get sedentary people off the couch or optimize athletic performance.  

But how could one’s microbiome impact the motivation to move? To find the answer, the researchers zeroed in on the brain. 
 

The gut-brain connection

After treating the mice with antibiotics, the researchers sequenced RNA in the rodents’ striatum (the part of the brain responsible for motivation). They found reduced gene expression in the cells’ dopamine receptors – which release the neurochemical dopamine, making one feel like they’ve accomplished something good. In other words: Mice treated with antibiotics were getting less of a dopamine hit after their run. 

“Only when we started focusing on the brain did we understand that the microbiome’s effect on exercise capacity was mediated by the central and peripheral nervous systems,” said study author Christoph Thaiss, PhD, a microbiologist at the University of Pennsylvania. “This realization completely changed the trajectory of the project.”

To find out how, exactly, bacteria in the colon were signaling the brain, the researchers performed a series of experiments over several years. They identified two types of bacteria, Eubacterium rectale and Coprococcus eutactus. These strains produce compounds called fatty acid amides that interact with endocannabinoid receptors in the gut. 

Those endocannabinoid receptors signal the brain to cut back its production of monoamine oxidase, the compound that breaks down dopamine. With less of this dopamine-clearing compound in the brain, more dopamine could build up after a long run, making the mice feel good and eager to hit the exercise wheel again soon. 

This gut-brain pathway “may have evolved to couple the initiation of prolonged physical activity to the nutritional status of the gastrointestinal tract,” Dr. Thaiss said. Gut bacteria monitor what’s in your colon and tell your brain whether you have enough food to fuel a workout. 

The colon, or gut, hosts trillions of microbes with potentially hundreds of different bacteria strains. These strains are determined by the food we eat and the environment we occupy.

“The genetic impact on the microbiome is rather minor,” Dr. Thaiss said, “but lifestyle factors strongly impact the composition of the gut microbiome.”

He hopes to develop nutritional interventions to encourage the growth of the motivating types of bacteria, the kind that make a person want to go for a 5-mile run.
 

What’s next?  

Moving forward,  the researchers need to find out whether the gut affects motivation in humans, too. To do that, they’re analyzing the gut microbiomes of people with varying levels of exercise motivation. 

“With enough samples, we could potentially correlate species of microbiota that exist in exercise-motivated individuals,” said study coauthor Nicholas Betley, PhD, a biologist at the University of Pennsylvania. 

Variations in the gut microbiome could help explain the “runner’s high” that some people have in a long-distance race. The research could also help promote weight training or sports participation. 

“Imagine if a sports team could optimally motivate the athletes on the team to exercise,” said Dr. Betley. The lab is investigating the microbiome’s impact on high-intensity interval training.

Signals from the gut to the brain could be affecting body processes in other ways too, the researchers speculated. 

“There are so many possibilities for how these signals may change physiology and impact health,” Dr. Betley said. “A new set of studies may well establish a whole new branch of exercise physiology.”

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

Could gut health be behind a person’s motivation – or lack thereof – to exercise?

Researchers at the University of Pennsylvania, Philadelphia recently explored this topic when they wanted to find out why some lab mice seem to love their exercise wheel, while others mostly ignore it.

To start, the researchers used a machine-learning algorithm to look for biological traits that could explain the differences in activity levels among mice. And what they found surprised them: Genetics seemed to have little to do with it, but differences in gut bacteria appeared to matter more. A handful of studies backed that up: Thriving gut microbiomes have been linked with optimal muscle function in mice.

Sure enough, when the researchers dosed mice with broad-spectrum antibiotics, killing off their gut bacteria, the distance the rodents were able to run dropped by half. But off the antibiotics, the mice mostly regained their previous performance levels.

The findings, published in the journal Nature, suggest that the gut microbiome may help regulate the desire to exercise. 

If confirmed in humans, this hypothesis could help explain why so many Americans fail to get the recommended amount of physical activity. Some may blame lack of time, energy, or interest. But perhaps the reason could come down to the trillions of microbes living in their gut. 

This line of research could also lead to microbiome-based ways to get sedentary people off the couch or optimize athletic performance.  

But how could one’s microbiome impact the motivation to move? To find the answer, the researchers zeroed in on the brain. 
 

The gut-brain connection

After treating the mice with antibiotics, the researchers sequenced RNA in the rodents’ striatum (the part of the brain responsible for motivation). They found reduced gene expression in the cells’ dopamine receptors – which release the neurochemical dopamine, making one feel like they’ve accomplished something good. In other words: Mice treated with antibiotics were getting less of a dopamine hit after their run. 

“Only when we started focusing on the brain did we understand that the microbiome’s effect on exercise capacity was mediated by the central and peripheral nervous systems,” said study author Christoph Thaiss, PhD, a microbiologist at the University of Pennsylvania. “This realization completely changed the trajectory of the project.”

To find out how, exactly, bacteria in the colon were signaling the brain, the researchers performed a series of experiments over several years. They identified two types of bacteria, Eubacterium rectale and Coprococcus eutactus. These strains produce compounds called fatty acid amides that interact with endocannabinoid receptors in the gut. 

Those endocannabinoid receptors signal the brain to cut back its production of monoamine oxidase, the compound that breaks down dopamine. With less of this dopamine-clearing compound in the brain, more dopamine could build up after a long run, making the mice feel good and eager to hit the exercise wheel again soon. 

This gut-brain pathway “may have evolved to couple the initiation of prolonged physical activity to the nutritional status of the gastrointestinal tract,” Dr. Thaiss said. Gut bacteria monitor what’s in your colon and tell your brain whether you have enough food to fuel a workout. 

The colon, or gut, hosts trillions of microbes with potentially hundreds of different bacteria strains. These strains are determined by the food we eat and the environment we occupy.

“The genetic impact on the microbiome is rather minor,” Dr. Thaiss said, “but lifestyle factors strongly impact the composition of the gut microbiome.”

He hopes to develop nutritional interventions to encourage the growth of the motivating types of bacteria, the kind that make a person want to go for a 5-mile run.
 

What’s next?  

Moving forward,  the researchers need to find out whether the gut affects motivation in humans, too. To do that, they’re analyzing the gut microbiomes of people with varying levels of exercise motivation. 

“With enough samples, we could potentially correlate species of microbiota that exist in exercise-motivated individuals,” said study coauthor Nicholas Betley, PhD, a biologist at the University of Pennsylvania. 

Variations in the gut microbiome could help explain the “runner’s high” that some people have in a long-distance race. The research could also help promote weight training or sports participation. 

“Imagine if a sports team could optimally motivate the athletes on the team to exercise,” said Dr. Betley. The lab is investigating the microbiome’s impact on high-intensity interval training.

Signals from the gut to the brain could be affecting body processes in other ways too, the researchers speculated. 

“There are so many possibilities for how these signals may change physiology and impact health,” Dr. Betley said. “A new set of studies may well establish a whole new branch of exercise physiology.”

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

Nine top professional emergency medicine organizations in the United States jointly issued a letter expressing concerns about the misleading and incomplete nature of a systematic review issued by the Agency for Healthcare Research and Quality on diagnostic errors in the emergency department.

The AHRQ review, issued on Dec. 15, 2022, stated that the findings of their study translate “to about 1 in 18 emergency department patients receiving an incorrect diagnosis, 1 in 50 suffering an adverse event, and 1 in 350 suffering permanent disability or death.” The authors describe these rates as similar to those seen in primary care and inpatient hospital settings.

The review was conducted through an Evidence-Based Practice Center as part of AHRQ’s Effective Health Care Program. The authors included data from 279 studies in the review. They identified the five most frequently misdiagnosed conditions in the ED as stroke, MI, aortic aneurysm and dissection, spinal cord compression and injury, and venous thromboembolism.

The authors noted that, given an estimated 130 million ED visits in the United States each year, the overall rate of incorrect diagnoses in the ED is approximately 5.7% and that 2.0% of the patients whose conditions were misdiagnosed suffer an adverse event as a result. On a local level, the authors estimate that an average ED with approximately 25,000 visits per year could experience 1,400 diagnostic errors, 500 diagnostic adverse events, and 75 serious harms, including 50 deaths. However, the authors noted that the overall error and harm rates were based on three studies from outside the United States (Canada, Spain, and Switzerland) and that only two of these were used to estimate harms.

“It’s imperative that we, as emergency physicians, inform the public that the AHRQ report used flawed methodology and statistics that extrapolated – and therefore overstated – the potential for harm when receiving care in US emergency departments,” Robert Glatter, MD, an emergency medicine physician at Lenox Hill Hospital at Northwell Health and an assistant professor at Hofstra University, Hempstead, N.Y., said in an interview.
 

Emergency medicine organizations express concerns for accuracy

The American College of Emergency Physicians and eight other medical organizations representing emergency medicine in the United States sent a letter to the AHRQ on Dec. 14, 2022, spelling out their concerns. The review was conducted as part of the AHRQ’s ongoing Effective Health Care Program, and the organizations had the opportunity to review a draft before it was published. On reading the review, they asked that the publication of the review be delayed. “After reviewing the executive summary and initial draft, we believe that the report makes misleading, incomplete, and erroneous conclusions from the literature reviewed and conveys a tone that inaccurately characterizes and unnecessarily disparages the practice of emergency medicine in the United States,” the organizations wrote in their letter.

The concerns of the emergency medicine organizations fell into four categories: misrepresentation of the practice and nature of emergency medicine; applicability of references cited; inaccurate interpretation of malpractice data; and the reporting of a single overall diagnostic error rate of 5.7% in EDs.

The practice of emergency medicine is variable and unique among specialties in that the focus is less about the final diagnosis and more about immediate identification and treatment of life-threatening conditions, according to the letter.

Notably, many of the studies cited did not mention whether the patient’s final diagnosis was apparent on admission to the ED. “Without this knowledge, it is completely inappropriate to label such discrepancies as ‘ED diagnostic error,’ ” the organizations wrote.

All medical specialties have room for improvement, but the current AHRQ review appears not to identify these opportunities, and instead of contributing to a discussion of improving patient care in the ED, it may cause harm by presenting misinformation, they said.
 

Misleading and inadequate evidence

“I strongly agree with the concerns mentioned from ACEP and other key organizations about the problems and conclusions reached in the AHRQ report,” Dr. Glatter said in an interview.

“The methodology used to arrive at the conclusions [in the review] was flawed and does not provide an accurate estimate of diagnostic error and, consequently, misdiagnosis and deaths occurring in emergency departments in the U.S.,” he said. “The startling headline that 250,000 people die annually in U.S. EDs was extrapolated from a single study based on one death that occurred in a Canadian ED in 2004,” Dr. Glatter noted. “Clearly, this is not only poor methodology but flawed science.”

The AHRQ report misused one death from this single study to estimate the death rate across the United States, Dr. Glatter explained, and this overestimate improperly inflated and magnified the number of potential patients that may have been harmed by physician error.

“This flawed evidence would actually place ED misdiagnoses in the top five causes of death in the United States, with 1 in every 500 ED patients dying as a result of an error by a physician. Simply put, there is just no evidence to support such a claim,” said Dr. Glatter.

The repercussions of the AHRQ review could be harmful to patients by instilling fear and doubt about the ability of emergency physicians to diagnose those who present with life-threatening conditions, Dr. Glatter said.

“This more balanced and accurate picture of the role of emergency physicians in diagnosing and managing such emergencies needs to be communicated to the public in order to reassure and instill confidence in our role in the sequence of emergency care in relation to continuity of care in patients presenting to the ED,” he said.

“While our primary role as emergency medicine physicians is to stabilize and evaluate patients, arriving at a particular diagnosis is not always possible for some conditions,” and additional diagnostic testing is often needed to identify more specific causes of symptoms, Dr. Glatter added.

Additional research is needed for a more accurate representation of diagnostic errors in the ED, said Dr. Glatter. New prospective studies are needed to address outcomes in U.S. EDs that account for the latest advances and diagnostic modalities in emergency medicine, “particularly advances in bedside ultrasound that can expedite critical decision-making, which can be lifesaving.

“The AHRQ report is simply not an accurate reflection of the technology and skill set that current emergency medicine practice offers our patients in 2023.”

Dr. Glatter disclosed no relevant financial relationships.

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

Nine top professional emergency medicine organizations in the United States jointly issued a letter expressing concerns about the misleading and incomplete nature of a systematic review issued by the Agency for Healthcare Research and Quality on diagnostic errors in the emergency department.

The AHRQ review, issued on Dec. 15, 2022, stated that the findings of their study translate “to about 1 in 18 emergency department patients receiving an incorrect diagnosis, 1 in 50 suffering an adverse event, and 1 in 350 suffering permanent disability or death.” The authors describe these rates as similar to those seen in primary care and inpatient hospital settings.

The review was conducted through an Evidence-Based Practice Center as part of AHRQ’s Effective Health Care Program. The authors included data from 279 studies in the review. They identified the five most frequently misdiagnosed conditions in the ED as stroke, MI, aortic aneurysm and dissection, spinal cord compression and injury, and venous thromboembolism.

The authors noted that, given an estimated 130 million ED visits in the United States each year, the overall rate of incorrect diagnoses in the ED is approximately 5.7% and that 2.0% of the patients whose conditions were misdiagnosed suffer an adverse event as a result. On a local level, the authors estimate that an average ED with approximately 25,000 visits per year could experience 1,400 diagnostic errors, 500 diagnostic adverse events, and 75 serious harms, including 50 deaths. However, the authors noted that the overall error and harm rates were based on three studies from outside the United States (Canada, Spain, and Switzerland) and that only two of these were used to estimate harms.

“It’s imperative that we, as emergency physicians, inform the public that the AHRQ report used flawed methodology and statistics that extrapolated – and therefore overstated – the potential for harm when receiving care in US emergency departments,” Robert Glatter, MD, an emergency medicine physician at Lenox Hill Hospital at Northwell Health and an assistant professor at Hofstra University, Hempstead, N.Y., said in an interview.
 

Emergency medicine organizations express concerns for accuracy

The American College of Emergency Physicians and eight other medical organizations representing emergency medicine in the United States sent a letter to the AHRQ on Dec. 14, 2022, spelling out their concerns. The review was conducted as part of the AHRQ’s ongoing Effective Health Care Program, and the organizations had the opportunity to review a draft before it was published. On reading the review, they asked that the publication of the review be delayed. “After reviewing the executive summary and initial draft, we believe that the report makes misleading, incomplete, and erroneous conclusions from the literature reviewed and conveys a tone that inaccurately characterizes and unnecessarily disparages the practice of emergency medicine in the United States,” the organizations wrote in their letter.

The concerns of the emergency medicine organizations fell into four categories: misrepresentation of the practice and nature of emergency medicine; applicability of references cited; inaccurate interpretation of malpractice data; and the reporting of a single overall diagnostic error rate of 5.7% in EDs.

The practice of emergency medicine is variable and unique among specialties in that the focus is less about the final diagnosis and more about immediate identification and treatment of life-threatening conditions, according to the letter.

Notably, many of the studies cited did not mention whether the patient’s final diagnosis was apparent on admission to the ED. “Without this knowledge, it is completely inappropriate to label such discrepancies as ‘ED diagnostic error,’ ” the organizations wrote.

All medical specialties have room for improvement, but the current AHRQ review appears not to identify these opportunities, and instead of contributing to a discussion of improving patient care in the ED, it may cause harm by presenting misinformation, they said.
 

Misleading and inadequate evidence

“I strongly agree with the concerns mentioned from ACEP and other key organizations about the problems and conclusions reached in the AHRQ report,” Dr. Glatter said in an interview.

“The methodology used to arrive at the conclusions [in the review] was flawed and does not provide an accurate estimate of diagnostic error and, consequently, misdiagnosis and deaths occurring in emergency departments in the U.S.,” he said. “The startling headline that 250,000 people die annually in U.S. EDs was extrapolated from a single study based on one death that occurred in a Canadian ED in 2004,” Dr. Glatter noted. “Clearly, this is not only poor methodology but flawed science.”

The AHRQ report misused one death from this single study to estimate the death rate across the United States, Dr. Glatter explained, and this overestimate improperly inflated and magnified the number of potential patients that may have been harmed by physician error.

“This flawed evidence would actually place ED misdiagnoses in the top five causes of death in the United States, with 1 in every 500 ED patients dying as a result of an error by a physician. Simply put, there is just no evidence to support such a claim,” said Dr. Glatter.

The repercussions of the AHRQ review could be harmful to patients by instilling fear and doubt about the ability of emergency physicians to diagnose those who present with life-threatening conditions, Dr. Glatter said.

“This more balanced and accurate picture of the role of emergency physicians in diagnosing and managing such emergencies needs to be communicated to the public in order to reassure and instill confidence in our role in the sequence of emergency care in relation to continuity of care in patients presenting to the ED,” he said.

“While our primary role as emergency medicine physicians is to stabilize and evaluate patients, arriving at a particular diagnosis is not always possible for some conditions,” and additional diagnostic testing is often needed to identify more specific causes of symptoms, Dr. Glatter added.

Additional research is needed for a more accurate representation of diagnostic errors in the ED, said Dr. Glatter. New prospective studies are needed to address outcomes in U.S. EDs that account for the latest advances and diagnostic modalities in emergency medicine, “particularly advances in bedside ultrasound that can expedite critical decision-making, which can be lifesaving.

“The AHRQ report is simply not an accurate reflection of the technology and skill set that current emergency medicine practice offers our patients in 2023.”

Dr. Glatter disclosed no relevant financial relationships.

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

Nine top professional emergency medicine organizations in the United States jointly issued a letter expressing concerns about the misleading and incomplete nature of a systematic review issued by the Agency for Healthcare Research and Quality on diagnostic errors in the emergency department.

The AHRQ review, issued on Dec. 15, 2022, stated that the findings of their study translate “to about 1 in 18 emergency department patients receiving an incorrect diagnosis, 1 in 50 suffering an adverse event, and 1 in 350 suffering permanent disability or death.” The authors describe these rates as similar to those seen in primary care and inpatient hospital settings.

The review was conducted through an Evidence-Based Practice Center as part of AHRQ’s Effective Health Care Program. The authors included data from 279 studies in the review. They identified the five most frequently misdiagnosed conditions in the ED as stroke, MI, aortic aneurysm and dissection, spinal cord compression and injury, and venous thromboembolism.

The authors noted that, given an estimated 130 million ED visits in the United States each year, the overall rate of incorrect diagnoses in the ED is approximately 5.7% and that 2.0% of the patients whose conditions were misdiagnosed suffer an adverse event as a result. On a local level, the authors estimate that an average ED with approximately 25,000 visits per year could experience 1,400 diagnostic errors, 500 diagnostic adverse events, and 75 serious harms, including 50 deaths. However, the authors noted that the overall error and harm rates were based on three studies from outside the United States (Canada, Spain, and Switzerland) and that only two of these were used to estimate harms.

“It’s imperative that we, as emergency physicians, inform the public that the AHRQ report used flawed methodology and statistics that extrapolated – and therefore overstated – the potential for harm when receiving care in US emergency departments,” Robert Glatter, MD, an emergency medicine physician at Lenox Hill Hospital at Northwell Health and an assistant professor at Hofstra University, Hempstead, N.Y., said in an interview.
 

Emergency medicine organizations express concerns for accuracy

The American College of Emergency Physicians and eight other medical organizations representing emergency medicine in the United States sent a letter to the AHRQ on Dec. 14, 2022, spelling out their concerns. The review was conducted as part of the AHRQ’s ongoing Effective Health Care Program, and the organizations had the opportunity to review a draft before it was published. On reading the review, they asked that the publication of the review be delayed. “After reviewing the executive summary and initial draft, we believe that the report makes misleading, incomplete, and erroneous conclusions from the literature reviewed and conveys a tone that inaccurately characterizes and unnecessarily disparages the practice of emergency medicine in the United States,” the organizations wrote in their letter.

The concerns of the emergency medicine organizations fell into four categories: misrepresentation of the practice and nature of emergency medicine; applicability of references cited; inaccurate interpretation of malpractice data; and the reporting of a single overall diagnostic error rate of 5.7% in EDs.

The practice of emergency medicine is variable and unique among specialties in that the focus is less about the final diagnosis and more about immediate identification and treatment of life-threatening conditions, according to the letter.

Notably, many of the studies cited did not mention whether the patient’s final diagnosis was apparent on admission to the ED. “Without this knowledge, it is completely inappropriate to label such discrepancies as ‘ED diagnostic error,’ ” the organizations wrote.

All medical specialties have room for improvement, but the current AHRQ review appears not to identify these opportunities, and instead of contributing to a discussion of improving patient care in the ED, it may cause harm by presenting misinformation, they said.
 

Misleading and inadequate evidence

“I strongly agree with the concerns mentioned from ACEP and other key organizations about the problems and conclusions reached in the AHRQ report,” Dr. Glatter said in an interview.

“The methodology used to arrive at the conclusions [in the review] was flawed and does not provide an accurate estimate of diagnostic error and, consequently, misdiagnosis and deaths occurring in emergency departments in the U.S.,” he said. “The startling headline that 250,000 people die annually in U.S. EDs was extrapolated from a single study based on one death that occurred in a Canadian ED in 2004,” Dr. Glatter noted. “Clearly, this is not only poor methodology but flawed science.”

The AHRQ report misused one death from this single study to estimate the death rate across the United States, Dr. Glatter explained, and this overestimate improperly inflated and magnified the number of potential patients that may have been harmed by physician error.

“This flawed evidence would actually place ED misdiagnoses in the top five causes of death in the United States, with 1 in every 500 ED patients dying as a result of an error by a physician. Simply put, there is just no evidence to support such a claim,” said Dr. Glatter.

The repercussions of the AHRQ review could be harmful to patients by instilling fear and doubt about the ability of emergency physicians to diagnose those who present with life-threatening conditions, Dr. Glatter said.

“This more balanced and accurate picture of the role of emergency physicians in diagnosing and managing such emergencies needs to be communicated to the public in order to reassure and instill confidence in our role in the sequence of emergency care in relation to continuity of care in patients presenting to the ED,” he said.

“While our primary role as emergency medicine physicians is to stabilize and evaluate patients, arriving at a particular diagnosis is not always possible for some conditions,” and additional diagnostic testing is often needed to identify more specific causes of symptoms, Dr. Glatter added.

Additional research is needed for a more accurate representation of diagnostic errors in the ED, said Dr. Glatter. New prospective studies are needed to address outcomes in U.S. EDs that account for the latest advances and diagnostic modalities in emergency medicine, “particularly advances in bedside ultrasound that can expedite critical decision-making, which can be lifesaving.

“The AHRQ report is simply not an accurate reflection of the technology and skill set that current emergency medicine practice offers our patients in 2023.”

Dr. Glatter disclosed no relevant financial relationships.

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

A group of emergency physicians and consumer advocates in multiple states is pushing for stiffer enforcement of decades-old statutes that prohibit the ownership of medical practices by corporations not owned by licensed doctors.

Thirty-three states plus the District of Columbia have rules on their books against the so-called corporate practice of medicine. But over the years, critics say, companies have successfully sidestepped bans on owning medical practices by buying or establishing local staffing groups that are nominally owned by doctors and restricting the physicians’ authority so they have no direct control.

These laws and regulations, which started appearing nearly a century ago, were meant to fight the commercialization of medicine, maintain the independence and authority of physicians, and prioritize the doctor-patient relationship over the interests of investors and shareholders.

Those campaigning for stiffer enforcement of the laws say that physician-staffing firms owned by private equity investors are the most egregious offenders. Private equity-backed staffing companies manage a quarter of the nation’s emergency departments, according to a Raleigh, N.C.–based doctor who runs a job site for ED physicians. The two largest are Nashville, Tenn.–based Envision Healthcare, owned by investment giant KKR & Co., and Knoxville, Tenn.–based TeamHealth, owned by Blackstone.

Court filings in multiple states, including California, Missouri, Texas, and Tennessee, have called out Envision and TeamHealth for allegedly using doctor groups as straw men to sidestep corporate practice laws. But those filings have typically been in financial cases involving wrongful termination, breach of contract, and overbilling.

Now, physicians and consumer advocates around the country are anticipating a California lawsuit against Envision, scheduled to start in January 2024 in federal court. The plaintiff in the case, Milwaukee-based American Academy of Emergency Medicine Physician Group, alleges that Envision uses shell business structures to retain de facto ownership of ED staffing groups, and it is asking the court to declare them illegal.

“We’re not asking them to pay money, and we will not accept being paid to drop the case,” said David Millstein, lead attorney for the plaintiff. “We are simply asking the court to ban this practice model.”
 

‘Possibility to reverberate throughout the country’

The physician group believes a victory would lead to a prohibition of the practice across California – and not just in ERs, but for other staff provided by Envision and TeamHealth, including in anesthesiology and hospital medicine. The California Medical Association supports the lawsuit, saying it “will shape the boundaries of California’s prohibition on the corporate practice of medicine.”

The plaintiff – along with many doctors, nurses, and consumer advocates, as well as some lawmakers – hopes that success in the case will spur regulators and prosecutors in other states to take corporate medicine prohibitions more seriously. “Any decision anywhere in the country that says the corporate ownership of a medical practice is illegal has the possibility to reverberate throughout the country, absolutely – and I hope that it would,” said Julie Mayfield, a state senator in North Carolina.

But the push to reinvigorate laws restricting the corporate practice of medicine has plenty of skeptics, who view it as an effort to return to a golden era in medicine that is long gone or may never have existed to begin with. The genie is out of the bottle, they say, noting that the profit motive has penetrated every corner of health care and that nearly 70% of physicians in the United States are now employed by corporations and hospitals.

The corporate practice of medicine doctrine has “a very interesting and not a very flattering history,” said Barak Richman, a law professor at Duke University. “The medical profession was trying to assert its professional dominance that accrued a lot of benefits to itself in ways that were not terribly beneficial to patients or to the market.”

The California case involves Placentia-Linda Hospital in Orange County, where the plaintiff physician group lost its ED management contract to Envision. The complaint alleges that Envision uses the same business model at numerous hospitals around the state.

“Envision exercises profound and pervasive direct and indirect control and/or influence over the medical practice, making decisions which bear directly and indirectly on the practice of medicine, rendering physicians as mere employees, and diminishing physician independence and freedom from commercial interests,” according to the complaint.

Envision said the company is compliant with state laws and that its operating structure is common in the health care industry. “Legal challenges to that structure have proved meritless,” Envision wrote in an email. It added that “care decisions have and always will be between clinicians and patients.”

TeamHealth, an indirect target in the case, said its “world-class operating team” provides management services that “allow clinicians to focus on the practice of medicine and patient care through a structure commonly utilized by hospitals, health systems, and other providers across the country.”
 

State rules vary widely

State laws and regulations governing the corporate practice of medicine vary widely on multiple factors, including whether there are exceptions for nonprofit organizations, how much of doctors’ revenue outside management firms can keep, who can own the equipment, and how violations are punished. New York, Texas, and California are considered to have among the toughest restrictions, while Florida and 16 other states have none.

Kirk Ogrosky, a partner at the law firm Goodwin Procter, said this kind of management structure predates the arrival of private equity in the industry. “I would be surprised if a company that is interested in investing in this space screwed up the formation documents; it would shock me,” Mr. Ogrosky said.

Private equity–backed firms have been attracted to EDs in recent years because they are profitable and because they have been able to charge inflated amounts for out-of-network care – at least until a federal law cracked down on surprise billing. Envision and TeamHealth prioritize profits, critics say, by maximizing revenue, cutting costs, and consolidating smaller practices into ever-larger groups – to the point of regional dominance.

Envision and TeamHealth are privately owned, which makes it difficult to find reliable data on their finances and the extent of their market penetration.

Leon Adelman, MD, cofounder and CEO of Ivy Clinicians, a Raleigh, N.C.–based startup job site for emergency physicians, has spent 18 months piecing together data and found that private equity–backed staffing firms run 25% of the nation’s EDs. TeamHealth and Envision have the two largest shares, with 8.6% and 8.3%, respectively, Dr. Adelman said.

Other estimates put private equity’s penetration of ERs at closer to 40%.
 

Doctors push for investigations

So far, efforts by emergency physicians and others to challenge private equity staffing firms over their alleged violations have yielded frustrating results.

An advocacy group called Take Medicine Back, formed last year by a handful of ED physicians, sent a letter in July to North Carolina Attorney General Josh Stein, asking him to investigate violations of the ban on the corporate practice of medicine. And because Mr. Stein holds a senior position at the National Association of Attorneys General, the letter also asked him to take the lead in persuading his fellow AGs to “launch a multi-state investigation into the widespread lack of enforcement” of corporate practice of medicine laws.

The group’s leader, Mitchell Li, MD, said he was initially disappointed by the response he received from Mr. Stein’s office, which promised to review his request, saying it raised complex legal issues about the corporate practice of medicine in the state. But Dr. Li is now more hopeful, since he has secured a January appointment with officials in Mr. Stein’s office.

Robert McNamara, MD, a cofounder of Dr. Li’s group and chair of emergency medicine at Temple University’s Lewis Katz School of Medicine, drafted complaints to the Texas Medical Board, along with Houston physician David Hoyer, MD, asking the board to intervene against two doctors accused of fronting for professional entities controlled by Envision and TeamHealth. In both cases, the board declined to intervene.

Dr. McNamara, who serves as the chief medical officer of the physicians’ group in the California Envision case, also filed a complaint with Pennsylvania Attorney General Josh Shapiro, alleging that a group called Emergency Care Services of Pennsylvania PC, which was trying to contract with ED physicians of the Crozer Keystone Health System, was wholly owned by TeamHealth and serving as a shell to avoid scrutiny.

A senior official in Mr. Shapiro’s office responded, saying the complaint had been referred to two state agencies, but Dr. McNamara said he has heard nothing back in more than 3 years.
 

Differing views on private equity’s role

Proponents of private equity ownership say it has brought a lot of good to health care. Jamal Hagler, vice president of research at the American Investment Council, said private equity brings expertise to hospital systems, “whether it’s to hire new staff, grow and open up to new markets, integrate new technologies, or develop new technologies.”

But many physicians who have worked for private equity companies say their mission is not compatible with the best practice of medicine. They cite an emphasis on speed and high patient volume over safety; a preference for lesser-trained, cheaper medical providers; and treatment protocols unsuitable for certain patients.

Sean Jones, MD, an emergency physician in Asheville, N.C., said his first full-time job was at a Florida hospital, where EmCare, a subsidiary of Envision, ran the ED. Dr. Jones said EmCare, in collaboration with the hospital’s owner, pushed doctors to meet performance goals related to wait times and treatments, which were not always good for patients.

For example, if a patient came in with abnormally high heart and respiratory rates – signs of sepsis – doctors were expected to give them large amounts of fluids and antibiotics within an hour, Dr. Jones said. But those symptoms could also be caused by a panic attack or heart failure.

“You don’t want to give a patient with heart failure 2 or 3 liters of fluid, and I would get emails saying, ‘You didn’t do this,’ ” he said. “Well, no, I didn’t, because the reason they couldn’t breathe was they had too much fluid in their lungs.”

Envision said the company’s 25,000 clinicians, “like all clinicians, exercise their independent judgment to provide quality, compassionate, clinically appropriate care.”

Dr. Jones felt otherwise. “We don’t need some MBAs telling us what to do,” he said.
 

This story was produced by KHN, which publishes California Healthline, an editorially independent service of the California Health Care Foundation. Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

A group of emergency physicians and consumer advocates in multiple states is pushing for stiffer enforcement of decades-old statutes that prohibit the ownership of medical practices by corporations not owned by licensed doctors.

Thirty-three states plus the District of Columbia have rules on their books against the so-called corporate practice of medicine. But over the years, critics say, companies have successfully sidestepped bans on owning medical practices by buying or establishing local staffing groups that are nominally owned by doctors and restricting the physicians’ authority so they have no direct control.

These laws and regulations, which started appearing nearly a century ago, were meant to fight the commercialization of medicine, maintain the independence and authority of physicians, and prioritize the doctor-patient relationship over the interests of investors and shareholders.

Those campaigning for stiffer enforcement of the laws say that physician-staffing firms owned by private equity investors are the most egregious offenders. Private equity-backed staffing companies manage a quarter of the nation’s emergency departments, according to a Raleigh, N.C.–based doctor who runs a job site for ED physicians. The two largest are Nashville, Tenn.–based Envision Healthcare, owned by investment giant KKR & Co., and Knoxville, Tenn.–based TeamHealth, owned by Blackstone.

Court filings in multiple states, including California, Missouri, Texas, and Tennessee, have called out Envision and TeamHealth for allegedly using doctor groups as straw men to sidestep corporate practice laws. But those filings have typically been in financial cases involving wrongful termination, breach of contract, and overbilling.

Now, physicians and consumer advocates around the country are anticipating a California lawsuit against Envision, scheduled to start in January 2024 in federal court. The plaintiff in the case, Milwaukee-based American Academy of Emergency Medicine Physician Group, alleges that Envision uses shell business structures to retain de facto ownership of ED staffing groups, and it is asking the court to declare them illegal.

“We’re not asking them to pay money, and we will not accept being paid to drop the case,” said David Millstein, lead attorney for the plaintiff. “We are simply asking the court to ban this practice model.”
 

‘Possibility to reverberate throughout the country’

The physician group believes a victory would lead to a prohibition of the practice across California – and not just in ERs, but for other staff provided by Envision and TeamHealth, including in anesthesiology and hospital medicine. The California Medical Association supports the lawsuit, saying it “will shape the boundaries of California’s prohibition on the corporate practice of medicine.”

The plaintiff – along with many doctors, nurses, and consumer advocates, as well as some lawmakers – hopes that success in the case will spur regulators and prosecutors in other states to take corporate medicine prohibitions more seriously. “Any decision anywhere in the country that says the corporate ownership of a medical practice is illegal has the possibility to reverberate throughout the country, absolutely – and I hope that it would,” said Julie Mayfield, a state senator in North Carolina.

But the push to reinvigorate laws restricting the corporate practice of medicine has plenty of skeptics, who view it as an effort to return to a golden era in medicine that is long gone or may never have existed to begin with. The genie is out of the bottle, they say, noting that the profit motive has penetrated every corner of health care and that nearly 70% of physicians in the United States are now employed by corporations and hospitals.

The corporate practice of medicine doctrine has “a very interesting and not a very flattering history,” said Barak Richman, a law professor at Duke University. “The medical profession was trying to assert its professional dominance that accrued a lot of benefits to itself in ways that were not terribly beneficial to patients or to the market.”

The California case involves Placentia-Linda Hospital in Orange County, where the plaintiff physician group lost its ED management contract to Envision. The complaint alleges that Envision uses the same business model at numerous hospitals around the state.

“Envision exercises profound and pervasive direct and indirect control and/or influence over the medical practice, making decisions which bear directly and indirectly on the practice of medicine, rendering physicians as mere employees, and diminishing physician independence and freedom from commercial interests,” according to the complaint.

Envision said the company is compliant with state laws and that its operating structure is common in the health care industry. “Legal challenges to that structure have proved meritless,” Envision wrote in an email. It added that “care decisions have and always will be between clinicians and patients.”

TeamHealth, an indirect target in the case, said its “world-class operating team” provides management services that “allow clinicians to focus on the practice of medicine and patient care through a structure commonly utilized by hospitals, health systems, and other providers across the country.”
 

State rules vary widely

State laws and regulations governing the corporate practice of medicine vary widely on multiple factors, including whether there are exceptions for nonprofit organizations, how much of doctors’ revenue outside management firms can keep, who can own the equipment, and how violations are punished. New York, Texas, and California are considered to have among the toughest restrictions, while Florida and 16 other states have none.

Kirk Ogrosky, a partner at the law firm Goodwin Procter, said this kind of management structure predates the arrival of private equity in the industry. “I would be surprised if a company that is interested in investing in this space screwed up the formation documents; it would shock me,” Mr. Ogrosky said.

Private equity–backed firms have been attracted to EDs in recent years because they are profitable and because they have been able to charge inflated amounts for out-of-network care – at least until a federal law cracked down on surprise billing. Envision and TeamHealth prioritize profits, critics say, by maximizing revenue, cutting costs, and consolidating smaller practices into ever-larger groups – to the point of regional dominance.

Envision and TeamHealth are privately owned, which makes it difficult to find reliable data on their finances and the extent of their market penetration.

Leon Adelman, MD, cofounder and CEO of Ivy Clinicians, a Raleigh, N.C.–based startup job site for emergency physicians, has spent 18 months piecing together data and found that private equity–backed staffing firms run 25% of the nation’s EDs. TeamHealth and Envision have the two largest shares, with 8.6% and 8.3%, respectively, Dr. Adelman said.

Other estimates put private equity’s penetration of ERs at closer to 40%.
 

Doctors push for investigations

So far, efforts by emergency physicians and others to challenge private equity staffing firms over their alleged violations have yielded frustrating results.

An advocacy group called Take Medicine Back, formed last year by a handful of ED physicians, sent a letter in July to North Carolina Attorney General Josh Stein, asking him to investigate violations of the ban on the corporate practice of medicine. And because Mr. Stein holds a senior position at the National Association of Attorneys General, the letter also asked him to take the lead in persuading his fellow AGs to “launch a multi-state investigation into the widespread lack of enforcement” of corporate practice of medicine laws.

The group’s leader, Mitchell Li, MD, said he was initially disappointed by the response he received from Mr. Stein’s office, which promised to review his request, saying it raised complex legal issues about the corporate practice of medicine in the state. But Dr. Li is now more hopeful, since he has secured a January appointment with officials in Mr. Stein’s office.

Robert McNamara, MD, a cofounder of Dr. Li’s group and chair of emergency medicine at Temple University’s Lewis Katz School of Medicine, drafted complaints to the Texas Medical Board, along with Houston physician David Hoyer, MD, asking the board to intervene against two doctors accused of fronting for professional entities controlled by Envision and TeamHealth. In both cases, the board declined to intervene.

Dr. McNamara, who serves as the chief medical officer of the physicians’ group in the California Envision case, also filed a complaint with Pennsylvania Attorney General Josh Shapiro, alleging that a group called Emergency Care Services of Pennsylvania PC, which was trying to contract with ED physicians of the Crozer Keystone Health System, was wholly owned by TeamHealth and serving as a shell to avoid scrutiny.

A senior official in Mr. Shapiro’s office responded, saying the complaint had been referred to two state agencies, but Dr. McNamara said he has heard nothing back in more than 3 years.
 

Differing views on private equity’s role

Proponents of private equity ownership say it has brought a lot of good to health care. Jamal Hagler, vice president of research at the American Investment Council, said private equity brings expertise to hospital systems, “whether it’s to hire new staff, grow and open up to new markets, integrate new technologies, or develop new technologies.”

But many physicians who have worked for private equity companies say their mission is not compatible with the best practice of medicine. They cite an emphasis on speed and high patient volume over safety; a preference for lesser-trained, cheaper medical providers; and treatment protocols unsuitable for certain patients.

Sean Jones, MD, an emergency physician in Asheville, N.C., said his first full-time job was at a Florida hospital, where EmCare, a subsidiary of Envision, ran the ED. Dr. Jones said EmCare, in collaboration with the hospital’s owner, pushed doctors to meet performance goals related to wait times and treatments, which were not always good for patients.

For example, if a patient came in with abnormally high heart and respiratory rates – signs of sepsis – doctors were expected to give them large amounts of fluids and antibiotics within an hour, Dr. Jones said. But those symptoms could also be caused by a panic attack or heart failure.

“You don’t want to give a patient with heart failure 2 or 3 liters of fluid, and I would get emails saying, ‘You didn’t do this,’ ” he said. “Well, no, I didn’t, because the reason they couldn’t breathe was they had too much fluid in their lungs.”

Envision said the company’s 25,000 clinicians, “like all clinicians, exercise their independent judgment to provide quality, compassionate, clinically appropriate care.”

Dr. Jones felt otherwise. “We don’t need some MBAs telling us what to do,” he said.
 

This story was produced by KHN, which publishes California Healthline, an editorially independent service of the California Health Care Foundation. Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

A group of emergency physicians and consumer advocates in multiple states is pushing for stiffer enforcement of decades-old statutes that prohibit the ownership of medical practices by corporations not owned by licensed doctors.

Thirty-three states plus the District of Columbia have rules on their books against the so-called corporate practice of medicine. But over the years, critics say, companies have successfully sidestepped bans on owning medical practices by buying or establishing local staffing groups that are nominally owned by doctors and restricting the physicians’ authority so they have no direct control.

These laws and regulations, which started appearing nearly a century ago, were meant to fight the commercialization of medicine, maintain the independence and authority of physicians, and prioritize the doctor-patient relationship over the interests of investors and shareholders.

Those campaigning for stiffer enforcement of the laws say that physician-staffing firms owned by private equity investors are the most egregious offenders. Private equity-backed staffing companies manage a quarter of the nation’s emergency departments, according to a Raleigh, N.C.–based doctor who runs a job site for ED physicians. The two largest are Nashville, Tenn.–based Envision Healthcare, owned by investment giant KKR & Co., and Knoxville, Tenn.–based TeamHealth, owned by Blackstone.

Court filings in multiple states, including California, Missouri, Texas, and Tennessee, have called out Envision and TeamHealth for allegedly using doctor groups as straw men to sidestep corporate practice laws. But those filings have typically been in financial cases involving wrongful termination, breach of contract, and overbilling.

Now, physicians and consumer advocates around the country are anticipating a California lawsuit against Envision, scheduled to start in January 2024 in federal court. The plaintiff in the case, Milwaukee-based American Academy of Emergency Medicine Physician Group, alleges that Envision uses shell business structures to retain de facto ownership of ED staffing groups, and it is asking the court to declare them illegal.

“We’re not asking them to pay money, and we will not accept being paid to drop the case,” said David Millstein, lead attorney for the plaintiff. “We are simply asking the court to ban this practice model.”
 

‘Possibility to reverberate throughout the country’

The physician group believes a victory would lead to a prohibition of the practice across California – and not just in ERs, but for other staff provided by Envision and TeamHealth, including in anesthesiology and hospital medicine. The California Medical Association supports the lawsuit, saying it “will shape the boundaries of California’s prohibition on the corporate practice of medicine.”

The plaintiff – along with many doctors, nurses, and consumer advocates, as well as some lawmakers – hopes that success in the case will spur regulators and prosecutors in other states to take corporate medicine prohibitions more seriously. “Any decision anywhere in the country that says the corporate ownership of a medical practice is illegal has the possibility to reverberate throughout the country, absolutely – and I hope that it would,” said Julie Mayfield, a state senator in North Carolina.

But the push to reinvigorate laws restricting the corporate practice of medicine has plenty of skeptics, who view it as an effort to return to a golden era in medicine that is long gone or may never have existed to begin with. The genie is out of the bottle, they say, noting that the profit motive has penetrated every corner of health care and that nearly 70% of physicians in the United States are now employed by corporations and hospitals.

The corporate practice of medicine doctrine has “a very interesting and not a very flattering history,” said Barak Richman, a law professor at Duke University. “The medical profession was trying to assert its professional dominance that accrued a lot of benefits to itself in ways that were not terribly beneficial to patients or to the market.”

The California case involves Placentia-Linda Hospital in Orange County, where the plaintiff physician group lost its ED management contract to Envision. The complaint alleges that Envision uses the same business model at numerous hospitals around the state.

“Envision exercises profound and pervasive direct and indirect control and/or influence over the medical practice, making decisions which bear directly and indirectly on the practice of medicine, rendering physicians as mere employees, and diminishing physician independence and freedom from commercial interests,” according to the complaint.

Envision said the company is compliant with state laws and that its operating structure is common in the health care industry. “Legal challenges to that structure have proved meritless,” Envision wrote in an email. It added that “care decisions have and always will be between clinicians and patients.”

TeamHealth, an indirect target in the case, said its “world-class operating team” provides management services that “allow clinicians to focus on the practice of medicine and patient care through a structure commonly utilized by hospitals, health systems, and other providers across the country.”
 

State rules vary widely

State laws and regulations governing the corporate practice of medicine vary widely on multiple factors, including whether there are exceptions for nonprofit organizations, how much of doctors’ revenue outside management firms can keep, who can own the equipment, and how violations are punished. New York, Texas, and California are considered to have among the toughest restrictions, while Florida and 16 other states have none.

Kirk Ogrosky, a partner at the law firm Goodwin Procter, said this kind of management structure predates the arrival of private equity in the industry. “I would be surprised if a company that is interested in investing in this space screwed up the formation documents; it would shock me,” Mr. Ogrosky said.

Private equity–backed firms have been attracted to EDs in recent years because they are profitable and because they have been able to charge inflated amounts for out-of-network care – at least until a federal law cracked down on surprise billing. Envision and TeamHealth prioritize profits, critics say, by maximizing revenue, cutting costs, and consolidating smaller practices into ever-larger groups – to the point of regional dominance.

Envision and TeamHealth are privately owned, which makes it difficult to find reliable data on their finances and the extent of their market penetration.

Leon Adelman, MD, cofounder and CEO of Ivy Clinicians, a Raleigh, N.C.–based startup job site for emergency physicians, has spent 18 months piecing together data and found that private equity–backed staffing firms run 25% of the nation’s EDs. TeamHealth and Envision have the two largest shares, with 8.6% and 8.3%, respectively, Dr. Adelman said.

Other estimates put private equity’s penetration of ERs at closer to 40%.
 

Doctors push for investigations

So far, efforts by emergency physicians and others to challenge private equity staffing firms over their alleged violations have yielded frustrating results.

An advocacy group called Take Medicine Back, formed last year by a handful of ED physicians, sent a letter in July to North Carolina Attorney General Josh Stein, asking him to investigate violations of the ban on the corporate practice of medicine. And because Mr. Stein holds a senior position at the National Association of Attorneys General, the letter also asked him to take the lead in persuading his fellow AGs to “launch a multi-state investigation into the widespread lack of enforcement” of corporate practice of medicine laws.

The group’s leader, Mitchell Li, MD, said he was initially disappointed by the response he received from Mr. Stein’s office, which promised to review his request, saying it raised complex legal issues about the corporate practice of medicine in the state. But Dr. Li is now more hopeful, since he has secured a January appointment with officials in Mr. Stein’s office.

Robert McNamara, MD, a cofounder of Dr. Li’s group and chair of emergency medicine at Temple University’s Lewis Katz School of Medicine, drafted complaints to the Texas Medical Board, along with Houston physician David Hoyer, MD, asking the board to intervene against two doctors accused of fronting for professional entities controlled by Envision and TeamHealth. In both cases, the board declined to intervene.

Dr. McNamara, who serves as the chief medical officer of the physicians’ group in the California Envision case, also filed a complaint with Pennsylvania Attorney General Josh Shapiro, alleging that a group called Emergency Care Services of Pennsylvania PC, which was trying to contract with ED physicians of the Crozer Keystone Health System, was wholly owned by TeamHealth and serving as a shell to avoid scrutiny.

A senior official in Mr. Shapiro’s office responded, saying the complaint had been referred to two state agencies, but Dr. McNamara said he has heard nothing back in more than 3 years.
 

Differing views on private equity’s role

Proponents of private equity ownership say it has brought a lot of good to health care. Jamal Hagler, vice president of research at the American Investment Council, said private equity brings expertise to hospital systems, “whether it’s to hire new staff, grow and open up to new markets, integrate new technologies, or develop new technologies.”

But many physicians who have worked for private equity companies say their mission is not compatible with the best practice of medicine. They cite an emphasis on speed and high patient volume over safety; a preference for lesser-trained, cheaper medical providers; and treatment protocols unsuitable for certain patients.

Sean Jones, MD, an emergency physician in Asheville, N.C., said his first full-time job was at a Florida hospital, where EmCare, a subsidiary of Envision, ran the ED. Dr. Jones said EmCare, in collaboration with the hospital’s owner, pushed doctors to meet performance goals related to wait times and treatments, which were not always good for patients.

For example, if a patient came in with abnormally high heart and respiratory rates – signs of sepsis – doctors were expected to give them large amounts of fluids and antibiotics within an hour, Dr. Jones said. But those symptoms could also be caused by a panic attack or heart failure.

“You don’t want to give a patient with heart failure 2 or 3 liters of fluid, and I would get emails saying, ‘You didn’t do this,’ ” he said. “Well, no, I didn’t, because the reason they couldn’t breathe was they had too much fluid in their lungs.”

Envision said the company’s 25,000 clinicians, “like all clinicians, exercise their independent judgment to provide quality, compassionate, clinically appropriate care.”

Dr. Jones felt otherwise. “We don’t need some MBAs telling us what to do,” he said.
 

This story was produced by KHN, which publishes California Healthline, an editorially independent service of the California Health Care Foundation. Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

With no proven treatments for long COVID, millions of Americans struggling with debilitating symptoms may be wondering whether it’s worth it to try something they’ve never considered before: a clinical trial. 

Dozens of clinical trials nationwide are already underway or starting soon, many of which are aided by $1.5 billion in funding from the National Institutes of Health to help identify new treatments for common symptoms like brain fog, fatigue, sleep disturbances, and a hard time breathing. But it may take years for these trials to prove which drugs, devices, and behavioral therapies are safe and effective. 

“We’re not in warp speed,” said Kanecia Zimmerman, MD, a principal investigator at the Duke Clinical Research Institute in Durham, N.C., who is overseeing long COVID trials for the NIH. Operation Warp Speed – the 2020-2021 federal effort to get COVID vaccines designed, tested, authorized and distributed – benefited from existing scientific knowledge about other coronaviruses and about vaccines in general. But there’s no similar foundation of scientific knowledge about long COVID. 

“We are in a place of not really knowing anything,” Dr. Zimmerman said.

But some glimmers of hope are emerging. A Veterans Affairs study recently found the antiviral Paxlovid might help prevent long COVID. A small case study at Yale found the ADHD drug guanfacine may ease brain fog from long COVID. And preliminary results from an NIH-funded study suggest COVID vaccines might help children with a rare but serious inflammatory condition known as multisystem inflammatory syndrome (MIS-C). 

More results are expected very soon from the trial for kids with MIS-C, which can strike suddenly long after a COVID infection clears up. While the exact causes aren’t yet clear, MIS-C can cause dangerous inflammation in the heart, lungs, kidneys, brain, skin, eyes, or gastrointestinal system. 

Because the virus often triggered a delayed response of MIS-C in kids who had few if any symptoms of acute COVID-19, scientists wondered whether children infected with the virus might respond to a vaccine dose to prevent MIS-C from developing, Gary Gibbons, MD, director of the National Heart, Lung, and Blood Institute, said during a Dec. 9 presentation at the NIH. It’s not yet clear if vaccination helps, but it doesn’t harm the children, Dr. Gibbons said. 

“Indeed, the studies suggest with some relief that yes, these children could be vaccinated safely,” he said. 

Several new trials are also testing Paxlovid against long COVID, including one late-stage study that may have results in about a year. 

“We already know that Paxlovid reduces the risk of developing long COVID, but it would be a game changer if it can improve long COVID symptoms as well,” said Surendra Barshikar, MD, an associate professor and medical director of the COVID Recover program at the University of Texas Southwestern Medical Center, Dallas. 

In other studies, researchers are looking at a wide variety of previously approved and experimental drugs and devices. For example, scientists in New York are testing the mood stabilizer lithium to treat brain fog and fatigue. And researchers in Illinois are investigating efgartigimod, a drug approved for the rare muscle-weakening autoimmune disorder myasthenia gravis, to see if it helps ease a long COVID complication known as POTS that can cause a sudden rapid heart rate and chronic fatigue. 

“The good news is that enrollment will proceed quickly, given the vast number of patients,” said Kristin Englund, MD, director of the reCOVer Center of Excellence at the Cleveland Clinic. 

This is all encouraging because roughly one in five American adults who have acute COVID infections develop persistent symptoms of long COVID, also known as post–acute sequelae of SARS-CoV-2 (PASC). And many of these long COVID patients have complex, overlapping clusters of symptoms that make traditional treatment approaches largely ineffective against this new, formidable disease. 

But not every patient living with long COVID will qualify for trials or find it easy to take part even if they do. Patients should consider how severe their symptoms are, the potential risks of any experimental treatments, and the many challenges they may have with getting to and from clinical trial sites that are largely concentrated around major cities and might be far from home. 

While this holds true for any type of trial, it’s essential for long COVID patients, who may have fatigue, muscle weakness, and other symptoms that make distance an impossible factor to ignore, said Aaron Friedberg, MD, clinical colead of the post–COVID-19 recovery program at the Ohio State University Wexner Medical Center, Columbus. 

“I think it is a personal decision, since the fatigue and pain that patients with PASC can experience can make it very challenging to travel long distances,” Dr. Friedberg said. “I would recommend calling or messaging ahead to find out exactly what type of travel might be required because there may be steps that can be completed by email or video, which could make it easier to participate, and some trials may be entirely remote.”

Even when patients feel up to the travel, they still might not be a good fit for a clinical trial. Scientists often look for people who didn’t have pre-existing health problems before they got long COVID, Dr. Barshikar noted. Patients taking medications may also be unable to participate in drug trials, particularly for experimental treatments because of concerns about unknown side effects from drug interactions. 

When clinical trials do seem like a good option, patients may want to consider seeking treatment at an academic medical center that is already doing long COVID research, particularly if their symptoms are too complex or severe to manage only through their primary care provider, said Jonathan Whiteson, MD, who helped draft long COVID treatment guidelines for the American Academy of Physical Medicine and Rehabilitation. He also serves as codirector of the New York University Langone Health post–COVID care program.

Many health care professionals on the front lines treating long COVID patients are optimistic that the sheer number of trials and the vast number of patients taking part should ultimately produce some better treatment options than people have right now. It’s just not going to happen overnight. 

“I suspect that while we will see some new treatments coming in the next 1-2 years, it may be several years before targets can be identified and full trials conducted to see results,” Dr. Friedberg said. “Getting good data takes time.”

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

With no proven treatments for long COVID, millions of Americans struggling with debilitating symptoms may be wondering whether it’s worth it to try something they’ve never considered before: a clinical trial. 

Dozens of clinical trials nationwide are already underway or starting soon, many of which are aided by $1.5 billion in funding from the National Institutes of Health to help identify new treatments for common symptoms like brain fog, fatigue, sleep disturbances, and a hard time breathing. But it may take years for these trials to prove which drugs, devices, and behavioral therapies are safe and effective. 

“We’re not in warp speed,” said Kanecia Zimmerman, MD, a principal investigator at the Duke Clinical Research Institute in Durham, N.C., who is overseeing long COVID trials for the NIH. Operation Warp Speed – the 2020-2021 federal effort to get COVID vaccines designed, tested, authorized and distributed – benefited from existing scientific knowledge about other coronaviruses and about vaccines in general. But there’s no similar foundation of scientific knowledge about long COVID. 

“We are in a place of not really knowing anything,” Dr. Zimmerman said.

But some glimmers of hope are emerging. A Veterans Affairs study recently found the antiviral Paxlovid might help prevent long COVID. A small case study at Yale found the ADHD drug guanfacine may ease brain fog from long COVID. And preliminary results from an NIH-funded study suggest COVID vaccines might help children with a rare but serious inflammatory condition known as multisystem inflammatory syndrome (MIS-C). 

More results are expected very soon from the trial for kids with MIS-C, which can strike suddenly long after a COVID infection clears up. While the exact causes aren’t yet clear, MIS-C can cause dangerous inflammation in the heart, lungs, kidneys, brain, skin, eyes, or gastrointestinal system. 

Because the virus often triggered a delayed response of MIS-C in kids who had few if any symptoms of acute COVID-19, scientists wondered whether children infected with the virus might respond to a vaccine dose to prevent MIS-C from developing, Gary Gibbons, MD, director of the National Heart, Lung, and Blood Institute, said during a Dec. 9 presentation at the NIH. It’s not yet clear if vaccination helps, but it doesn’t harm the children, Dr. Gibbons said. 

“Indeed, the studies suggest with some relief that yes, these children could be vaccinated safely,” he said. 

Several new trials are also testing Paxlovid against long COVID, including one late-stage study that may have results in about a year. 

“We already know that Paxlovid reduces the risk of developing long COVID, but it would be a game changer if it can improve long COVID symptoms as well,” said Surendra Barshikar, MD, an associate professor and medical director of the COVID Recover program at the University of Texas Southwestern Medical Center, Dallas. 

In other studies, researchers are looking at a wide variety of previously approved and experimental drugs and devices. For example, scientists in New York are testing the mood stabilizer lithium to treat brain fog and fatigue. And researchers in Illinois are investigating efgartigimod, a drug approved for the rare muscle-weakening autoimmune disorder myasthenia gravis, to see if it helps ease a long COVID complication known as POTS that can cause a sudden rapid heart rate and chronic fatigue. 

“The good news is that enrollment will proceed quickly, given the vast number of patients,” said Kristin Englund, MD, director of the reCOVer Center of Excellence at the Cleveland Clinic. 

This is all encouraging because roughly one in five American adults who have acute COVID infections develop persistent symptoms of long COVID, also known as post–acute sequelae of SARS-CoV-2 (PASC). And many of these long COVID patients have complex, overlapping clusters of symptoms that make traditional treatment approaches largely ineffective against this new, formidable disease. 

But not every patient living with long COVID will qualify for trials or find it easy to take part even if they do. Patients should consider how severe their symptoms are, the potential risks of any experimental treatments, and the many challenges they may have with getting to and from clinical trial sites that are largely concentrated around major cities and might be far from home. 

While this holds true for any type of trial, it’s essential for long COVID patients, who may have fatigue, muscle weakness, and other symptoms that make distance an impossible factor to ignore, said Aaron Friedberg, MD, clinical colead of the post–COVID-19 recovery program at the Ohio State University Wexner Medical Center, Columbus. 

“I think it is a personal decision, since the fatigue and pain that patients with PASC can experience can make it very challenging to travel long distances,” Dr. Friedberg said. “I would recommend calling or messaging ahead to find out exactly what type of travel might be required because there may be steps that can be completed by email or video, which could make it easier to participate, and some trials may be entirely remote.”

Even when patients feel up to the travel, they still might not be a good fit for a clinical trial. Scientists often look for people who didn’t have pre-existing health problems before they got long COVID, Dr. Barshikar noted. Patients taking medications may also be unable to participate in drug trials, particularly for experimental treatments because of concerns about unknown side effects from drug interactions. 

When clinical trials do seem like a good option, patients may want to consider seeking treatment at an academic medical center that is already doing long COVID research, particularly if their symptoms are too complex or severe to manage only through their primary care provider, said Jonathan Whiteson, MD, who helped draft long COVID treatment guidelines for the American Academy of Physical Medicine and Rehabilitation. He also serves as codirector of the New York University Langone Health post–COVID care program.

Many health care professionals on the front lines treating long COVID patients are optimistic that the sheer number of trials and the vast number of patients taking part should ultimately produce some better treatment options than people have right now. It’s just not going to happen overnight. 

“I suspect that while we will see some new treatments coming in the next 1-2 years, it may be several years before targets can be identified and full trials conducted to see results,” Dr. Friedberg said. “Getting good data takes time.”

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

With no proven treatments for long COVID, millions of Americans struggling with debilitating symptoms may be wondering whether it’s worth it to try something they’ve never considered before: a clinical trial. 

Dozens of clinical trials nationwide are already underway or starting soon, many of which are aided by $1.5 billion in funding from the National Institutes of Health to help identify new treatments for common symptoms like brain fog, fatigue, sleep disturbances, and a hard time breathing. But it may take years for these trials to prove which drugs, devices, and behavioral therapies are safe and effective. 

“We’re not in warp speed,” said Kanecia Zimmerman, MD, a principal investigator at the Duke Clinical Research Institute in Durham, N.C., who is overseeing long COVID trials for the NIH. Operation Warp Speed – the 2020-2021 federal effort to get COVID vaccines designed, tested, authorized and distributed – benefited from existing scientific knowledge about other coronaviruses and about vaccines in general. But there’s no similar foundation of scientific knowledge about long COVID. 

“We are in a place of not really knowing anything,” Dr. Zimmerman said.

But some glimmers of hope are emerging. A Veterans Affairs study recently found the antiviral Paxlovid might help prevent long COVID. A small case study at Yale found the ADHD drug guanfacine may ease brain fog from long COVID. And preliminary results from an NIH-funded study suggest COVID vaccines might help children with a rare but serious inflammatory condition known as multisystem inflammatory syndrome (MIS-C). 

More results are expected very soon from the trial for kids with MIS-C, which can strike suddenly long after a COVID infection clears up. While the exact causes aren’t yet clear, MIS-C can cause dangerous inflammation in the heart, lungs, kidneys, brain, skin, eyes, or gastrointestinal system. 

Because the virus often triggered a delayed response of MIS-C in kids who had few if any symptoms of acute COVID-19, scientists wondered whether children infected with the virus might respond to a vaccine dose to prevent MIS-C from developing, Gary Gibbons, MD, director of the National Heart, Lung, and Blood Institute, said during a Dec. 9 presentation at the NIH. It’s not yet clear if vaccination helps, but it doesn’t harm the children, Dr. Gibbons said. 

“Indeed, the studies suggest with some relief that yes, these children could be vaccinated safely,” he said. 

Several new trials are also testing Paxlovid against long COVID, including one late-stage study that may have results in about a year. 

“We already know that Paxlovid reduces the risk of developing long COVID, but it would be a game changer if it can improve long COVID symptoms as well,” said Surendra Barshikar, MD, an associate professor and medical director of the COVID Recover program at the University of Texas Southwestern Medical Center, Dallas. 

In other studies, researchers are looking at a wide variety of previously approved and experimental drugs and devices. For example, scientists in New York are testing the mood stabilizer lithium to treat brain fog and fatigue. And researchers in Illinois are investigating efgartigimod, a drug approved for the rare muscle-weakening autoimmune disorder myasthenia gravis, to see if it helps ease a long COVID complication known as POTS that can cause a sudden rapid heart rate and chronic fatigue. 

“The good news is that enrollment will proceed quickly, given the vast number of patients,” said Kristin Englund, MD, director of the reCOVer Center of Excellence at the Cleveland Clinic. 

This is all encouraging because roughly one in five American adults who have acute COVID infections develop persistent symptoms of long COVID, also known as post–acute sequelae of SARS-CoV-2 (PASC). And many of these long COVID patients have complex, overlapping clusters of symptoms that make traditional treatment approaches largely ineffective against this new, formidable disease. 

But not every patient living with long COVID will qualify for trials or find it easy to take part even if they do. Patients should consider how severe their symptoms are, the potential risks of any experimental treatments, and the many challenges they may have with getting to and from clinical trial sites that are largely concentrated around major cities and might be far from home. 

While this holds true for any type of trial, it’s essential for long COVID patients, who may have fatigue, muscle weakness, and other symptoms that make distance an impossible factor to ignore, said Aaron Friedberg, MD, clinical colead of the post–COVID-19 recovery program at the Ohio State University Wexner Medical Center, Columbus. 

“I think it is a personal decision, since the fatigue and pain that patients with PASC can experience can make it very challenging to travel long distances,” Dr. Friedberg said. “I would recommend calling or messaging ahead to find out exactly what type of travel might be required because there may be steps that can be completed by email or video, which could make it easier to participate, and some trials may be entirely remote.”

Even when patients feel up to the travel, they still might not be a good fit for a clinical trial. Scientists often look for people who didn’t have pre-existing health problems before they got long COVID, Dr. Barshikar noted. Patients taking medications may also be unable to participate in drug trials, particularly for experimental treatments because of concerns about unknown side effects from drug interactions. 

When clinical trials do seem like a good option, patients may want to consider seeking treatment at an academic medical center that is already doing long COVID research, particularly if their symptoms are too complex or severe to manage only through their primary care provider, said Jonathan Whiteson, MD, who helped draft long COVID treatment guidelines for the American Academy of Physical Medicine and Rehabilitation. He also serves as codirector of the New York University Langone Health post–COVID care program.

Many health care professionals on the front lines treating long COVID patients are optimistic that the sheer number of trials and the vast number of patients taking part should ultimately produce some better treatment options than people have right now. It’s just not going to happen overnight. 

“I suspect that while we will see some new treatments coming in the next 1-2 years, it may be several years before targets can be identified and full trials conducted to see results,” Dr. Friedberg said. “Getting good data takes time.”

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

Strict control of comorbidities in patients with chronic obstructive pulmonary disease decreases exacerbations and morbimortality, and avoids readmissions. An increasing number of women have the disease, which progresses differently in women than in men and even has different comorbidities.

“Comorbidities in patients with chronic obstructive pulmonary disease are more common in older adults, in those with more advanced pulmonary disease, and in those that are hospitalized for an acute exacerbation,” said Belén Alonso, MD, PhD, coordinator of the COPD Working Group of the Spanish Society of Internal Medicine. Up to 73 comorbidities associated with chronic obstructive pulmonary disease have been described. Dr. Alonso made these remarks during her presentation at the Comorbidities in Chronic Obstructive Pulmonary Disease Panel, which took place during the 43rd Conference of the Spanish Society of Internal Medicine (SEMI), in Gijón, Spain.

According to the scientific society’s press release, moderator María Gómez Antúnez, MD, stated, “The correct approach and treatment of these comorbidities is fundamental to improve the quality of life of the patient, decrease exacerbations, avoid readmissions, and decrease morbimortality in people with chronic obstructive pulmonary disease.”

The different works published, two of them by the SEMI COPD Working Group (ECCO and ESMI studies), indicate that the main comorbidities of patients with that pneumopathy are arterial hypertension, dyslipidemia, diabetes, heart failure, atrial fibrillation, ischemic heart disease, chronic kidney disease, peripheral arterial disease, and osteoporosis. Chronic hepatopathy, pulmonary neoplasm, depression, and cerebrovascular disease are less common.
 

73 comorbidities described

Dr. Alonso told this news organization, “Of those 73 comorbidities, some of the lesser known or less attention grabbing, according to a paper that we brought to the panel, include sleep disorders that encompass insomnia, nightmares, night terrors, sleep apneas, or hypopneas. Other lesser-known comorbidities related to cognitive decline, with patterns that reflect that up to 60% [of patients] may have some degree of deterioration, involve the disease phase, hypoxemia, or degree of inflammation. On the other hand, it has also been associated with Parkinson’s disease and gastroesophageal reflux, among many more that arise from the cardiovascular sphere.”

One paper reveals that more than 78% of patients with chronic obstructive pulmonary disease have one associated comorbidity, almost 69% have two, and 47.9% have three.

“Based on gender, comorbidities are different. In women, it is well observed that anxiety, depression, and osteoporosis are more common. However, hypertension, ischemic heart disease, and diabetes are more common in men with chronic obstructive pulmonary disease,” she stated.

“The pulmonary disease in question also progresses differently in men and women. In women, onset is at younger ages – between 40 and 50 years – and in men, after 50. Likewise, it appears that the disease progresses more quickly, which coincides with a worse quality of life (since dyspnea is tolerated less) and exceeds the anatomical differences, where hormonal influences play a dominant role,” Dr. Alonso stressed.
 

Reciprocal prognosis

Dr. Alonso stated, “The prognostic importance of comorbidities in the disease is reciprocal. In other words, if there are comorbidities that we do not look for or treat, they are going to have a negative influence on the chronic obstructive pulmonary disease. The disease will progress more and elevate the risk of exacerbations (the most important prognostic factor of that disease). In turn, if we are not treating the disease well, not only pharmacologically, it will have negative repercussions on the comorbidities. It will progress and have negative connotations, such as diabetes or ischemic heart disease.”

The aforementioned ECCO and ESMI studies include patients in internal medicine with exacerbations where the most common comorbidities have been mapped out, although there is also extensive research on comorbidities in patients who are admitted to departments other than internal medicine. “With regard to prognostic implications, our working group very clearly observed the comorbidities and the comorbidome, that solar system that appears so much in medical conferences and forums, which implies that proximity to the center of that solar system is related more to mortality, anxiety, depression, and breast cancer. Other pathologies, such as ischemic heart disease or dyslipidemia, are outside of that territory of greater risk, in which we have been more pioneering than other groups,” said Dr. Alonso.

The current trend is that the age of these patients is increasing, and there are more and more women with this pathology. According to the latest report from the Ministry of Health on respiratory diseases, the prevalence of chronic obstructive pulmonary disease among the population 40 years and older is around 33.9 cases per 1,000 inhabitants, more than twice as common in men than in women (47.7 vs. 21.3). Prevalence increases with age after 40 years progressively until reaching the greatest frequency in the 80- to 84-year-old age group.

In 2019, the number of deaths due to chronic obstructive pulmonary disease in Spain was 13,808 (9,907 men and 3,901 women), with a crude mortality rate of 29.3 deaths per 100,000 inhabitants. This toll decreased in comparison with that of 2018. Chronic obstructive pulmonary disease causes 2.5 times more deaths in men than in women. From 2001 to 2019, mortality due to that pathology declined by 43% in men and women. The decrease was almost 50% in men and 33% in women.
 

Overlap syndrome prevalent

Javier Sánchez Lora, MD, of the internal medicine department of the Virgen de la Victoria de Málaga University Clinical Hospital, discussed chronic obstructive pulmonary disease and sleep disorders. More concretely, he spoke about overlap syndrome: chronic obstructive pulmonary disease plus obstructive sleep apnea. According to the international consensus document on obstructive sleep apnea, the diagnosis requires an apnea-hypopnea index (AHI) equal to or greater than 15 per hour or equal to or greater than 5. The patient must also have one or more of the following factors: excessive daytime sleepiness, sleep that is not restful, excessive fatigue, and deterioration in quality of life related to sleep and not justified by other causes.

“The overlap syndrome affects 3%-66% of chronic obstructive pulmonary diseases and 7%-55% of obstructive sleep apnea,” said Dr. Sánchez Lora. This syndrome has important effects on different systems: at the cardiovascular level (arterial and pulmonary hypertension, heart failure, stroke, arrhythmias, ischemic heart disease, pulmonary thromboembolism), metabolic (insulin resistance, diabetes, metabolic syndrome), neurocognitive (dementia, depression), and neoplastic (lung, pancreas, esophagus) effects.

“These patients have a worse prognosis than those that have these pathologies alone. During sleep, they experience more frequent episodes of oxygen desaturation and they have a longer total period of sleep with hypoxemia and hypercapnia than those with obstructive apnea alone without chronic obstructive pulmonary disease,” said Dr. Sánchez Lora.

The apneic events of patients with the syndrome have a more profound hypoxemia and more arrhythmias, in addition to them being more susceptible to developing pulmonary hypertension than those with chronic obstructive pulmonary disease or sleep apnea alone. “The good news is that in patients with overlap, the use of ventilation with positive pressure reduces all causes of hospitalization and the visits to the emergency room, as well as the moderate and severe exacerbations of the disease.”

Dr. Sánchez Lora referred to a series of recommendations in clinical practice for the diagnosis and treatment of overlap syndrome: screening, combined therapy of hygienic-dietary measures, and the use of continuous positive respiratory pressure. Oxygen therapy to correct isolated nocturnal desaturations has not shown benefits in survival, although a benefit trial of symptoms attributed to nocturnal hypoxemia in patients with significant comorbidity can be conducted.
 

Underdiagnosis

“During the panel, we also spoke about the importance that as part of internal medicine we need to make an effort to reduce the underdiagnosis of chronic pulmonary disease and its comorbidities. Specialists in internal medicine need to become aware that this pathology is not only pulmonary, but also multisystemic, complex, heterogenous, and very variable even in the same patient,” said Dr. Sánchez Lora.

Dr. Alonso said, “Regarding the importance of diagnosis of this disease, we continue with an underdiagnosis greater than 70% for men and 80% for women. Secondly, we need to actively seek out the comorbidities associated with chronic obstructive pulmonary disease, even taking advantage of the admission of these patients with exacerbations, which are undesired and common.

“Regarding ongoing trials, we have a study that started during the COVID-19 pandemic, ADEG-EPOC, that involves the adaptation to and impact of severe and very severe exacerbations in patients admitted to our departments,” the specialist indicated.

“In the group, we are also planning to publish an updated agreement, which we already made in 2014, on the most common and important comorbidities associated with chronic obstructive pulmonary disease.” The agreement discusses the 20 most important comorbidities. In addition, the 2023 Gold Guide, which appeared in November 2022, includes a new chapter on updated treatment and the latest developments.

In the last 5 years, Dr. Alonso has collaborated with Abbott, AstraZeneca, Boehringer Ingelheim, Chiesi, FAES, Ferrer, Fresenius Kabi, GSK, Nestlé, Novo Nordisk, Nutricia, and Menarini. Dr. Sánchez Lora has collaborated with AstraZeneca, Boehringer Ingelheim, Chiesi, FAES, GSK, and Menarini.

This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.

Strict control of comorbidities in patients with chronic obstructive pulmonary disease decreases exacerbations and morbimortality, and avoids readmissions. An increasing number of women have the disease, which progresses differently in women than in men and even has different comorbidities.

“Comorbidities in patients with chronic obstructive pulmonary disease are more common in older adults, in those with more advanced pulmonary disease, and in those that are hospitalized for an acute exacerbation,” said Belén Alonso, MD, PhD, coordinator of the COPD Working Group of the Spanish Society of Internal Medicine. Up to 73 comorbidities associated with chronic obstructive pulmonary disease have been described. Dr. Alonso made these remarks during her presentation at the Comorbidities in Chronic Obstructive Pulmonary Disease Panel, which took place during the 43rd Conference of the Spanish Society of Internal Medicine (SEMI), in Gijón, Spain.

According to the scientific society’s press release, moderator María Gómez Antúnez, MD, stated, “The correct approach and treatment of these comorbidities is fundamental to improve the quality of life of the patient, decrease exacerbations, avoid readmissions, and decrease morbimortality in people with chronic obstructive pulmonary disease.”

The different works published, two of them by the SEMI COPD Working Group (ECCO and ESMI studies), indicate that the main comorbidities of patients with that pneumopathy are arterial hypertension, dyslipidemia, diabetes, heart failure, atrial fibrillation, ischemic heart disease, chronic kidney disease, peripheral arterial disease, and osteoporosis. Chronic hepatopathy, pulmonary neoplasm, depression, and cerebrovascular disease are less common.
 

73 comorbidities described

Dr. Alonso told this news organization, “Of those 73 comorbidities, some of the lesser known or less attention grabbing, according to a paper that we brought to the panel, include sleep disorders that encompass insomnia, nightmares, night terrors, sleep apneas, or hypopneas. Other lesser-known comorbidities related to cognitive decline, with patterns that reflect that up to 60% [of patients] may have some degree of deterioration, involve the disease phase, hypoxemia, or degree of inflammation. On the other hand, it has also been associated with Parkinson’s disease and gastroesophageal reflux, among many more that arise from the cardiovascular sphere.”

One paper reveals that more than 78% of patients with chronic obstructive pulmonary disease have one associated comorbidity, almost 69% have two, and 47.9% have three.

“Based on gender, comorbidities are different. In women, it is well observed that anxiety, depression, and osteoporosis are more common. However, hypertension, ischemic heart disease, and diabetes are more common in men with chronic obstructive pulmonary disease,” she stated.

“The pulmonary disease in question also progresses differently in men and women. In women, onset is at younger ages – between 40 and 50 years – and in men, after 50. Likewise, it appears that the disease progresses more quickly, which coincides with a worse quality of life (since dyspnea is tolerated less) and exceeds the anatomical differences, where hormonal influences play a dominant role,” Dr. Alonso stressed.
 

Reciprocal prognosis

Dr. Alonso stated, “The prognostic importance of comorbidities in the disease is reciprocal. In other words, if there are comorbidities that we do not look for or treat, they are going to have a negative influence on the chronic obstructive pulmonary disease. The disease will progress more and elevate the risk of exacerbations (the most important prognostic factor of that disease). In turn, if we are not treating the disease well, not only pharmacologically, it will have negative repercussions on the comorbidities. It will progress and have negative connotations, such as diabetes or ischemic heart disease.”

The aforementioned ECCO and ESMI studies include patients in internal medicine with exacerbations where the most common comorbidities have been mapped out, although there is also extensive research on comorbidities in patients who are admitted to departments other than internal medicine. “With regard to prognostic implications, our working group very clearly observed the comorbidities and the comorbidome, that solar system that appears so much in medical conferences and forums, which implies that proximity to the center of that solar system is related more to mortality, anxiety, depression, and breast cancer. Other pathologies, such as ischemic heart disease or dyslipidemia, are outside of that territory of greater risk, in which we have been more pioneering than other groups,” said Dr. Alonso.

The current trend is that the age of these patients is increasing, and there are more and more women with this pathology. According to the latest report from the Ministry of Health on respiratory diseases, the prevalence of chronic obstructive pulmonary disease among the population 40 years and older is around 33.9 cases per 1,000 inhabitants, more than twice as common in men than in women (47.7 vs. 21.3). Prevalence increases with age after 40 years progressively until reaching the greatest frequency in the 80- to 84-year-old age group.

In 2019, the number of deaths due to chronic obstructive pulmonary disease in Spain was 13,808 (9,907 men and 3,901 women), with a crude mortality rate of 29.3 deaths per 100,000 inhabitants. This toll decreased in comparison with that of 2018. Chronic obstructive pulmonary disease causes 2.5 times more deaths in men than in women. From 2001 to 2019, mortality due to that pathology declined by 43% in men and women. The decrease was almost 50% in men and 33% in women.
 

Overlap syndrome prevalent

Javier Sánchez Lora, MD, of the internal medicine department of the Virgen de la Victoria de Málaga University Clinical Hospital, discussed chronic obstructive pulmonary disease and sleep disorders. More concretely, he spoke about overlap syndrome: chronic obstructive pulmonary disease plus obstructive sleep apnea. According to the international consensus document on obstructive sleep apnea, the diagnosis requires an apnea-hypopnea index (AHI) equal to or greater than 15 per hour or equal to or greater than 5. The patient must also have one or more of the following factors: excessive daytime sleepiness, sleep that is not restful, excessive fatigue, and deterioration in quality of life related to sleep and not justified by other causes.

“The overlap syndrome affects 3%-66% of chronic obstructive pulmonary diseases and 7%-55% of obstructive sleep apnea,” said Dr. Sánchez Lora. This syndrome has important effects on different systems: at the cardiovascular level (arterial and pulmonary hypertension, heart failure, stroke, arrhythmias, ischemic heart disease, pulmonary thromboembolism), metabolic (insulin resistance, diabetes, metabolic syndrome), neurocognitive (dementia, depression), and neoplastic (lung, pancreas, esophagus) effects.

“These patients have a worse prognosis than those that have these pathologies alone. During sleep, they experience more frequent episodes of oxygen desaturation and they have a longer total period of sleep with hypoxemia and hypercapnia than those with obstructive apnea alone without chronic obstructive pulmonary disease,” said Dr. Sánchez Lora.

The apneic events of patients with the syndrome have a more profound hypoxemia and more arrhythmias, in addition to them being more susceptible to developing pulmonary hypertension than those with chronic obstructive pulmonary disease or sleep apnea alone. “The good news is that in patients with overlap, the use of ventilation with positive pressure reduces all causes of hospitalization and the visits to the emergency room, as well as the moderate and severe exacerbations of the disease.”

Dr. Sánchez Lora referred to a series of recommendations in clinical practice for the diagnosis and treatment of overlap syndrome: screening, combined therapy of hygienic-dietary measures, and the use of continuous positive respiratory pressure. Oxygen therapy to correct isolated nocturnal desaturations has not shown benefits in survival, although a benefit trial of symptoms attributed to nocturnal hypoxemia in patients with significant comorbidity can be conducted.
 

Underdiagnosis

“During the panel, we also spoke about the importance that as part of internal medicine we need to make an effort to reduce the underdiagnosis of chronic pulmonary disease and its comorbidities. Specialists in internal medicine need to become aware that this pathology is not only pulmonary, but also multisystemic, complex, heterogenous, and very variable even in the same patient,” said Dr. Sánchez Lora.

Dr. Alonso said, “Regarding the importance of diagnosis of this disease, we continue with an underdiagnosis greater than 70% for men and 80% for women. Secondly, we need to actively seek out the comorbidities associated with chronic obstructive pulmonary disease, even taking advantage of the admission of these patients with exacerbations, which are undesired and common.

“Regarding ongoing trials, we have a study that started during the COVID-19 pandemic, ADEG-EPOC, that involves the adaptation to and impact of severe and very severe exacerbations in patients admitted to our departments,” the specialist indicated.

“In the group, we are also planning to publish an updated agreement, which we already made in 2014, on the most common and important comorbidities associated with chronic obstructive pulmonary disease.” The agreement discusses the 20 most important comorbidities. In addition, the 2023 Gold Guide, which appeared in November 2022, includes a new chapter on updated treatment and the latest developments.

In the last 5 years, Dr. Alonso has collaborated with Abbott, AstraZeneca, Boehringer Ingelheim, Chiesi, FAES, Ferrer, Fresenius Kabi, GSK, Nestlé, Novo Nordisk, Nutricia, and Menarini. Dr. Sánchez Lora has collaborated with AstraZeneca, Boehringer Ingelheim, Chiesi, FAES, GSK, and Menarini.

This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.

Strict control of comorbidities in patients with chronic obstructive pulmonary disease decreases exacerbations and morbimortality, and avoids readmissions. An increasing number of women have the disease, which progresses differently in women than in men and even has different comorbidities.

“Comorbidities in patients with chronic obstructive pulmonary disease are more common in older adults, in those with more advanced pulmonary disease, and in those that are hospitalized for an acute exacerbation,” said Belén Alonso, MD, PhD, coordinator of the COPD Working Group of the Spanish Society of Internal Medicine. Up to 73 comorbidities associated with chronic obstructive pulmonary disease have been described. Dr. Alonso made these remarks during her presentation at the Comorbidities in Chronic Obstructive Pulmonary Disease Panel, which took place during the 43rd Conference of the Spanish Society of Internal Medicine (SEMI), in Gijón, Spain.

According to the scientific society’s press release, moderator María Gómez Antúnez, MD, stated, “The correct approach and treatment of these comorbidities is fundamental to improve the quality of life of the patient, decrease exacerbations, avoid readmissions, and decrease morbimortality in people with chronic obstructive pulmonary disease.”

The different works published, two of them by the SEMI COPD Working Group (ECCO and ESMI studies), indicate that the main comorbidities of patients with that pneumopathy are arterial hypertension, dyslipidemia, diabetes, heart failure, atrial fibrillation, ischemic heart disease, chronic kidney disease, peripheral arterial disease, and osteoporosis. Chronic hepatopathy, pulmonary neoplasm, depression, and cerebrovascular disease are less common.
 

73 comorbidities described

Dr. Alonso told this news organization, “Of those 73 comorbidities, some of the lesser known or less attention grabbing, according to a paper that we brought to the panel, include sleep disorders that encompass insomnia, nightmares, night terrors, sleep apneas, or hypopneas. Other lesser-known comorbidities related to cognitive decline, with patterns that reflect that up to 60% [of patients] may have some degree of deterioration, involve the disease phase, hypoxemia, or degree of inflammation. On the other hand, it has also been associated with Parkinson’s disease and gastroesophageal reflux, among many more that arise from the cardiovascular sphere.”

One paper reveals that more than 78% of patients with chronic obstructive pulmonary disease have one associated comorbidity, almost 69% have two, and 47.9% have three.

“Based on gender, comorbidities are different. In women, it is well observed that anxiety, depression, and osteoporosis are more common. However, hypertension, ischemic heart disease, and diabetes are more common in men with chronic obstructive pulmonary disease,” she stated.

“The pulmonary disease in question also progresses differently in men and women. In women, onset is at younger ages – between 40 and 50 years – and in men, after 50. Likewise, it appears that the disease progresses more quickly, which coincides with a worse quality of life (since dyspnea is tolerated less) and exceeds the anatomical differences, where hormonal influences play a dominant role,” Dr. Alonso stressed.
 

Reciprocal prognosis

Dr. Alonso stated, “The prognostic importance of comorbidities in the disease is reciprocal. In other words, if there are comorbidities that we do not look for or treat, they are going to have a negative influence on the chronic obstructive pulmonary disease. The disease will progress more and elevate the risk of exacerbations (the most important prognostic factor of that disease). In turn, if we are not treating the disease well, not only pharmacologically, it will have negative repercussions on the comorbidities. It will progress and have negative connotations, such as diabetes or ischemic heart disease.”

The aforementioned ECCO and ESMI studies include patients in internal medicine with exacerbations where the most common comorbidities have been mapped out, although there is also extensive research on comorbidities in patients who are admitted to departments other than internal medicine. “With regard to prognostic implications, our working group very clearly observed the comorbidities and the comorbidome, that solar system that appears so much in medical conferences and forums, which implies that proximity to the center of that solar system is related more to mortality, anxiety, depression, and breast cancer. Other pathologies, such as ischemic heart disease or dyslipidemia, are outside of that territory of greater risk, in which we have been more pioneering than other groups,” said Dr. Alonso.

The current trend is that the age of these patients is increasing, and there are more and more women with this pathology. According to the latest report from the Ministry of Health on respiratory diseases, the prevalence of chronic obstructive pulmonary disease among the population 40 years and older is around 33.9 cases per 1,000 inhabitants, more than twice as common in men than in women (47.7 vs. 21.3). Prevalence increases with age after 40 years progressively until reaching the greatest frequency in the 80- to 84-year-old age group.

In 2019, the number of deaths due to chronic obstructive pulmonary disease in Spain was 13,808 (9,907 men and 3,901 women), with a crude mortality rate of 29.3 deaths per 100,000 inhabitants. This toll decreased in comparison with that of 2018. Chronic obstructive pulmonary disease causes 2.5 times more deaths in men than in women. From 2001 to 2019, mortality due to that pathology declined by 43% in men and women. The decrease was almost 50% in men and 33% in women.
 

Overlap syndrome prevalent

Javier Sánchez Lora, MD, of the internal medicine department of the Virgen de la Victoria de Málaga University Clinical Hospital, discussed chronic obstructive pulmonary disease and sleep disorders. More concretely, he spoke about overlap syndrome: chronic obstructive pulmonary disease plus obstructive sleep apnea. According to the international consensus document on obstructive sleep apnea, the diagnosis requires an apnea-hypopnea index (AHI) equal to or greater than 15 per hour or equal to or greater than 5. The patient must also have one or more of the following factors: excessive daytime sleepiness, sleep that is not restful, excessive fatigue, and deterioration in quality of life related to sleep and not justified by other causes.

“The overlap syndrome affects 3%-66% of chronic obstructive pulmonary diseases and 7%-55% of obstructive sleep apnea,” said Dr. Sánchez Lora. This syndrome has important effects on different systems: at the cardiovascular level (arterial and pulmonary hypertension, heart failure, stroke, arrhythmias, ischemic heart disease, pulmonary thromboembolism), metabolic (insulin resistance, diabetes, metabolic syndrome), neurocognitive (dementia, depression), and neoplastic (lung, pancreas, esophagus) effects.

“These patients have a worse prognosis than those that have these pathologies alone. During sleep, they experience more frequent episodes of oxygen desaturation and they have a longer total period of sleep with hypoxemia and hypercapnia than those with obstructive apnea alone without chronic obstructive pulmonary disease,” said Dr. Sánchez Lora.

The apneic events of patients with the syndrome have a more profound hypoxemia and more arrhythmias, in addition to them being more susceptible to developing pulmonary hypertension than those with chronic obstructive pulmonary disease or sleep apnea alone. “The good news is that in patients with overlap, the use of ventilation with positive pressure reduces all causes of hospitalization and the visits to the emergency room, as well as the moderate and severe exacerbations of the disease.”

Dr. Sánchez Lora referred to a series of recommendations in clinical practice for the diagnosis and treatment of overlap syndrome: screening, combined therapy of hygienic-dietary measures, and the use of continuous positive respiratory pressure. Oxygen therapy to correct isolated nocturnal desaturations has not shown benefits in survival, although a benefit trial of symptoms attributed to nocturnal hypoxemia in patients with significant comorbidity can be conducted.
 

Underdiagnosis

“During the panel, we also spoke about the importance that as part of internal medicine we need to make an effort to reduce the underdiagnosis of chronic pulmonary disease and its comorbidities. Specialists in internal medicine need to become aware that this pathology is not only pulmonary, but also multisystemic, complex, heterogenous, and very variable even in the same patient,” said Dr. Sánchez Lora.

Dr. Alonso said, “Regarding the importance of diagnosis of this disease, we continue with an underdiagnosis greater than 70% for men and 80% for women. Secondly, we need to actively seek out the comorbidities associated with chronic obstructive pulmonary disease, even taking advantage of the admission of these patients with exacerbations, which are undesired and common.

“Regarding ongoing trials, we have a study that started during the COVID-19 pandemic, ADEG-EPOC, that involves the adaptation to and impact of severe and very severe exacerbations in patients admitted to our departments,” the specialist indicated.

“In the group, we are also planning to publish an updated agreement, which we already made in 2014, on the most common and important comorbidities associated with chronic obstructive pulmonary disease.” The agreement discusses the 20 most important comorbidities. In addition, the 2023 Gold Guide, which appeared in November 2022, includes a new chapter on updated treatment and the latest developments.

In the last 5 years, Dr. Alonso has collaborated with Abbott, AstraZeneca, Boehringer Ingelheim, Chiesi, FAES, Ferrer, Fresenius Kabi, GSK, Nestlé, Novo Nordisk, Nutricia, and Menarini. Dr. Sánchez Lora has collaborated with AstraZeneca, Boehringer Ingelheim, Chiesi, FAES, GSK, and Menarini.

This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.

We wish you a merry Christmas and a happy heart failure

Does anyone really like it when places of business send out cards or messages for the holidays? A card from a truly small family business is one thing, but when you start getting emails from multibillion dollar corporations, it feels a bit dishonest. And that’s not even mentioning the potential blowback when things go wrong.

Petr Kratochvil

Now, you may wonder how a company could possibly mess up something so simple. “We wish you a merry Christmas and a happy New Year.” Not that difficult. Unless you’re Askern Medical Practice in Doncaster, England. Instead of expressing a simple expression of joy for the holiday season, Askern informed all 8,000 of its patients that they had aggressive lung cancer with metastases and they needed to fill out a DS1500 form, which entitles terminal patients to certain benefits.

It only took an hour for Askern to recognize its mistake and send a second text apologizing and adding in the appropriate season’s greetings, but obviously the damage was done. Presumably patients who were last at the doctor to have their cold treated were able to shrug off the text, or simply didn’t see it before the correction came through, but obviously many patients had concerns directly related to cancer and panicked. They called in but were by and large unable to reach anyone at the practice. Some patients close by even went to center itself to clear things up.

One patient, Mr. Carl Chegwin, raised an excellent point about the debacle: “What if that message was meant for someone, and then they are told it’s a Christmas message, then again told, ‘Oh no, that was actually meant for you?’ ” The old double backtrack into yes, you actually do have cancer has got to be a candidate for worst Christmas gift of all. Yes, even worse than socks.
 

Genes know it: You are when you eat

There’s been a lot of recent research on intermittent fasting and what it can and can’t do for one’s health. Much of it has focused on participants’ metabolic rates, but a study just published in Cell Metabolism shows how time-restricted feeding (TRF) has an impact on gene expression, the process through which genes are activated and respond to their environment by creating proteins.

Salk Institute

The research conducted by Satchidananda Panda, PhD, of the Salk Institute and his team involved two groups of mice, one with free access to food and the other with a daily 9-hour feeding window. Analysis of tissue samples collected from 22 organ groups revealed that nearly 80% of mouse genes responded to TRF. Interestingly, 40% of the genes in the hypothalamus, adrenal gland, and pancreas, which handle hormone regulation, were affected, suggesting that TRF could potentially aid in diabetes and stress disorder management, the investigators said in a written statement.

The researchers also found that TRF aligned the circadian rhythms of multiple organs of the body, which brings sleep into the picture. “Time-restricted eating synchronized the circadian rhythms to have two major waves: one during fasting, and another just after eating. We suspect this allows the body to coordinate different processes,” said Dr. Panda, whose previous research looked at TRF in firefighters, who typically work on shift schedules.

Time-restricted eating, it appears, affects gene expression throughout the body and allows interconnected organ systems to work smoothly. It’s not just about eating. Go figure.
 

This group practice reduced stress for everyone

It’s been awhile since we checked in on the good folks at Maharishi International University in Fairfield, Iowa – fictional home of the Fighting Transcendentalists [MAHARISHI RULES!] – but we just have to mention their long-term effort to reduce the national stress.

Goodboy Picture Company/E+/Getty Images

Way back in the year 2000, a group from MIU began practicing transcendental meditation. The size of the group increased over the next few years and eventually reached 1,725 in 2006. That number is important because it represents the square root of 1% of the U.S. population. When that “transition threshold was achieved,” the university explained in a written statement, “all stress indicators immediately started decreasing.”

By stress indicators they mean the U.S. stress index, the mean of eight variables – murder, rape, assault, robbery, infant mortality, drug deaths, vehicle fatalities, and child deaths by injuries – that the study investigators used to track the effectiveness of the meditation program, they said in the World Journal of Social Science.

After 2011, “when the size of the group size began to decline the rate of decrease in stress slowed and then it reversed and began to increase,” MIU reported.

Coauthor Dr. Kenneth Cavanaugh of MIU explained the process: “This study used state-of-the-art methods of time series regression analysis for eliminating potential alternative explanations due to intrinsic preexisting trends and fluctuations in the data. We carefully studied potential alternative explanations in terms of changes in economic conditions, political leadership, population demographics, and policing strategies. None of these factors could account for the results.”

Since we here at LOTME are serious professional journalists, the use of quotes means we are not making this up. Here’s one more thing in quotes: “A grant for 75 million dollars from the Howard and Alice Settle Foundation provided stipends for participants to be in the group and provided funding to bring several hundred visiting [meditation] experts from India to further augment the MIU group.”

Who needs to make up stuff? Not us.

We wish you a merry Christmas and a happy heart failure

Does anyone really like it when places of business send out cards or messages for the holidays? A card from a truly small family business is one thing, but when you start getting emails from multibillion dollar corporations, it feels a bit dishonest. And that’s not even mentioning the potential blowback when things go wrong.

Petr Kratochvil

Now, you may wonder how a company could possibly mess up something so simple. “We wish you a merry Christmas and a happy New Year.” Not that difficult. Unless you’re Askern Medical Practice in Doncaster, England. Instead of expressing a simple expression of joy for the holiday season, Askern informed all 8,000 of its patients that they had aggressive lung cancer with metastases and they needed to fill out a DS1500 form, which entitles terminal patients to certain benefits.

It only took an hour for Askern to recognize its mistake and send a second text apologizing and adding in the appropriate season’s greetings, but obviously the damage was done. Presumably patients who were last at the doctor to have their cold treated were able to shrug off the text, or simply didn’t see it before the correction came through, but obviously many patients had concerns directly related to cancer and panicked. They called in but were by and large unable to reach anyone at the practice. Some patients close by even went to center itself to clear things up.

One patient, Mr. Carl Chegwin, raised an excellent point about the debacle: “What if that message was meant for someone, and then they are told it’s a Christmas message, then again told, ‘Oh no, that was actually meant for you?’ ” The old double backtrack into yes, you actually do have cancer has got to be a candidate for worst Christmas gift of all. Yes, even worse than socks.
 

Genes know it: You are when you eat

There’s been a lot of recent research on intermittent fasting and what it can and can’t do for one’s health. Much of it has focused on participants’ metabolic rates, but a study just published in Cell Metabolism shows how time-restricted feeding (TRF) has an impact on gene expression, the process through which genes are activated and respond to their environment by creating proteins.

Salk Institute

The research conducted by Satchidananda Panda, PhD, of the Salk Institute and his team involved two groups of mice, one with free access to food and the other with a daily 9-hour feeding window. Analysis of tissue samples collected from 22 organ groups revealed that nearly 80% of mouse genes responded to TRF. Interestingly, 40% of the genes in the hypothalamus, adrenal gland, and pancreas, which handle hormone regulation, were affected, suggesting that TRF could potentially aid in diabetes and stress disorder management, the investigators said in a written statement.

The researchers also found that TRF aligned the circadian rhythms of multiple organs of the body, which brings sleep into the picture. “Time-restricted eating synchronized the circadian rhythms to have two major waves: one during fasting, and another just after eating. We suspect this allows the body to coordinate different processes,” said Dr. Panda, whose previous research looked at TRF in firefighters, who typically work on shift schedules.

Time-restricted eating, it appears, affects gene expression throughout the body and allows interconnected organ systems to work smoothly. It’s not just about eating. Go figure.
 

This group practice reduced stress for everyone

It’s been awhile since we checked in on the good folks at Maharishi International University in Fairfield, Iowa – fictional home of the Fighting Transcendentalists [MAHARISHI RULES!] – but we just have to mention their long-term effort to reduce the national stress.

Goodboy Picture Company/E+/Getty Images

Way back in the year 2000, a group from MIU began practicing transcendental meditation. The size of the group increased over the next few years and eventually reached 1,725 in 2006. That number is important because it represents the square root of 1% of the U.S. population. When that “transition threshold was achieved,” the university explained in a written statement, “all stress indicators immediately started decreasing.”

By stress indicators they mean the U.S. stress index, the mean of eight variables – murder, rape, assault, robbery, infant mortality, drug deaths, vehicle fatalities, and child deaths by injuries – that the study investigators used to track the effectiveness of the meditation program, they said in the World Journal of Social Science.

After 2011, “when the size of the group size began to decline the rate of decrease in stress slowed and then it reversed and began to increase,” MIU reported.

Coauthor Dr. Kenneth Cavanaugh of MIU explained the process: “This study used state-of-the-art methods of time series regression analysis for eliminating potential alternative explanations due to intrinsic preexisting trends and fluctuations in the data. We carefully studied potential alternative explanations in terms of changes in economic conditions, political leadership, population demographics, and policing strategies. None of these factors could account for the results.”

Since we here at LOTME are serious professional journalists, the use of quotes means we are not making this up. Here’s one more thing in quotes: “A grant for 75 million dollars from the Howard and Alice Settle Foundation provided stipends for participants to be in the group and provided funding to bring several hundred visiting [meditation] experts from India to further augment the MIU group.”

Who needs to make up stuff? Not us.

We wish you a merry Christmas and a happy heart failure

Does anyone really like it when places of business send out cards or messages for the holidays? A card from a truly small family business is one thing, but when you start getting emails from multibillion dollar corporations, it feels a bit dishonest. And that’s not even mentioning the potential blowback when things go wrong.

Petr Kratochvil

Now, you may wonder how a company could possibly mess up something so simple. “We wish you a merry Christmas and a happy New Year.” Not that difficult. Unless you’re Askern Medical Practice in Doncaster, England. Instead of expressing a simple expression of joy for the holiday season, Askern informed all 8,000 of its patients that they had aggressive lung cancer with metastases and they needed to fill out a DS1500 form, which entitles terminal patients to certain benefits.

It only took an hour for Askern to recognize its mistake and send a second text apologizing and adding in the appropriate season’s greetings, but obviously the damage was done. Presumably patients who were last at the doctor to have their cold treated were able to shrug off the text, or simply didn’t see it before the correction came through, but obviously many patients had concerns directly related to cancer and panicked. They called in but were by and large unable to reach anyone at the practice. Some patients close by even went to center itself to clear things up.

One patient, Mr. Carl Chegwin, raised an excellent point about the debacle: “What if that message was meant for someone, and then they are told it’s a Christmas message, then again told, ‘Oh no, that was actually meant for you?’ ” The old double backtrack into yes, you actually do have cancer has got to be a candidate for worst Christmas gift of all. Yes, even worse than socks.
 

Genes know it: You are when you eat

There’s been a lot of recent research on intermittent fasting and what it can and can’t do for one’s health. Much of it has focused on participants’ metabolic rates, but a study just published in Cell Metabolism shows how time-restricted feeding (TRF) has an impact on gene expression, the process through which genes are activated and respond to their environment by creating proteins.

Salk Institute

The research conducted by Satchidananda Panda, PhD, of the Salk Institute and his team involved two groups of mice, one with free access to food and the other with a daily 9-hour feeding window. Analysis of tissue samples collected from 22 organ groups revealed that nearly 80% of mouse genes responded to TRF. Interestingly, 40% of the genes in the hypothalamus, adrenal gland, and pancreas, which handle hormone regulation, were affected, suggesting that TRF could potentially aid in diabetes and stress disorder management, the investigators said in a written statement.

The researchers also found that TRF aligned the circadian rhythms of multiple organs of the body, which brings sleep into the picture. “Time-restricted eating synchronized the circadian rhythms to have two major waves: one during fasting, and another just after eating. We suspect this allows the body to coordinate different processes,” said Dr. Panda, whose previous research looked at TRF in firefighters, who typically work on shift schedules.

Time-restricted eating, it appears, affects gene expression throughout the body and allows interconnected organ systems to work smoothly. It’s not just about eating. Go figure.
 

This group practice reduced stress for everyone

It’s been awhile since we checked in on the good folks at Maharishi International University in Fairfield, Iowa – fictional home of the Fighting Transcendentalists [MAHARISHI RULES!] – but we just have to mention their long-term effort to reduce the national stress.

Goodboy Picture Company/E+/Getty Images

Way back in the year 2000, a group from MIU began practicing transcendental meditation. The size of the group increased over the next few years and eventually reached 1,725 in 2006. That number is important because it represents the square root of 1% of the U.S. population. When that “transition threshold was achieved,” the university explained in a written statement, “all stress indicators immediately started decreasing.”

By stress indicators they mean the U.S. stress index, the mean of eight variables – murder, rape, assault, robbery, infant mortality, drug deaths, vehicle fatalities, and child deaths by injuries – that the study investigators used to track the effectiveness of the meditation program, they said in the World Journal of Social Science.

After 2011, “when the size of the group size began to decline the rate of decrease in stress slowed and then it reversed and began to increase,” MIU reported.

Coauthor Dr. Kenneth Cavanaugh of MIU explained the process: “This study used state-of-the-art methods of time series regression analysis for eliminating potential alternative explanations due to intrinsic preexisting trends and fluctuations in the data. We carefully studied potential alternative explanations in terms of changes in economic conditions, political leadership, population demographics, and policing strategies. None of these factors could account for the results.”

Since we here at LOTME are serious professional journalists, the use of quotes means we are not making this up. Here’s one more thing in quotes: “A grant for 75 million dollars from the Howard and Alice Settle Foundation provided stipends for participants to be in the group and provided funding to bring several hundred visiting [meditation] experts from India to further augment the MIU group.”

Who needs to make up stuff? Not us.

The American College of Physicians has updated their guideline for pharmacotherapy to reduce fracture risk in adults with primary osteoporosis or osteopenia (low bone mass) based on a systematic review of the evidence.

This is the first update for 5 years since the previous guidance was published in 2017.

It strongly recommends initial therapy with bisphosphonates for postmenopausal women with osteoporosis, as well as men with osteoporosis, among other recommendations.

However, the author of an accompanying editorial, Susan M. Ott, MD, says: “The decision to start a bisphosphonate is actually not that easy.”

She also queries some of the other recommendations in the guidance.

Her editorial, along with the guideline by Amir Qaseem, MD, PhD, MPH, and colleagues, and systematic review by Chelsea Ayers, MPH, and colleagues, were published in the Annals of Internal Medicine.

Ryan D. Mire, MD, MACP, president of the ACP, gave a brief overview of the new guidance in a video.
 

Systematic review

The ACP commissioned a review of the evidence because it says new data have emerged on the efficacy of newer medications for osteoporosis and low bone mass, as well as treatment comparisons, and treatment in men.

The review authors identified 34 randomized controlled trials (in 100 publications) and 36 observational studies, which evaluated the following pharmacologic interventions:

• Antiresorptive drugs: four bisphosphonates (alendronate, ibandronate, risedronate, zoledronate) and a RANK ligand inhibitor (denosumab).
• Anabolic drugs: an analog of human parathyroid hormone (PTH)–related protein (abaloparatide), recombinant human PTH (teriparatide), and a sclerostin inhibitor (romosozumab).
• Estrogen agonists: selective estrogen receptor modulators (bazedoxifene, raloxifene).

The authors focused on effectiveness and harms of active drugs compared with placebo or bisphosphonates.
 

Major changes from 2017 guidelines, some questions

“Though there are many nuanced changes in this [2023 guideline] version, perhaps the major change is the explicit hierarchy of pharmacologic recommendations: bisphosphonates first, then denosumab,” Thomas G. Cooney, MD, senior author of the clinical guideline, explained in an interview.

“Bisphosphonates had the most favorable balance among benefits, harms, patient values and preferences, and cost among the examined drugs in postmenopausal females with primary osteoporosis,” Dr. Cooney, professor of medicine, Oregon Health & Science University, Portland, noted, as is stated in the guideline.

“Denosumab also had a favorable long-term net benefit, but bisphosphonates are much cheaper than other pharmacologic treatments and available in generic formulations,” the document states.

The new guideline suggests use of denosumab as second-line pharmacotherapy in adults who have contraindications to or experience adverse effects with bisphosphonates.

The choice among bisphosphonates (alendronate, risedronate, zoledronic acid) would be based on a patient-centered discussion between physician and patient, addressing costs (often related to insurance), delivery-mode preferences (oral versus intravenous), and “values,” which includes the patient’s priorities, concerns, and expectations regarding their health care, Dr. Cooney explained.

Another update in the new guideline is, “We also clarify the specific, albeit more limited, role of sclerostin inhibitors and recombinant PTH ‘to reduce the risk of fractures only in females with primary osteoporosis with very high-risk of fracture’,” Dr. Cooney noted.

In addition, the guideline now states, “treatment to reduce the risk of fractures in males rather than limiting it to ‘vertebral fracture’ in men,” as in the 2017 guideline.

It also explicitly includes denosumab as second-line therapy for men, Dr. Cooney noted, but as in 2017, the strength of evidence in men remains low.

“Finally, we also clarified that in females over the age of 65 with low bone mass or osteopenia that an individualized approach be taken to treatment (similar to last guideline), but if treatment is initiated, that a bisphosphonate be used (new content),” he said.

The use of estrogen, treatment duration, drug discontinuation, and serial bone mineral density monitoring were not addressed in this guideline, but will likely be evaluated within 2 to 3 years.
 

‘Osteoporosis treatment: Not easy’ – editorial

In her editorial, Dr. Ott writes: “The data about bisphosphonates may seem overwhelmingly positive, leading to strong recommendations for their use to treat osteoporosis, but the decision to start a bisphosphonate is actually not that easy.”

“A strong recommendation should be given only when future studies are unlikely to change it,” continues Dr. Ott, professor of medicine, University of Washington, Seattle.

“Yet, data already suggest that, in patients with serious osteoporosis, treatment should start with anabolic medications because previous treatment with either bisphosphonates or denosumab will prevent the anabolic response of newer medications.”

“Starting with bisphosphonate will change the bone so it will not respond to the newer medicines, and then a patient will lose the chance for getting the best improvement,” Dr. Ott clarified in an email to this news organization.

But, in fact, the new guidance does suggest that, to reduce the risk of fractures in females with primary osteoporosis at very high risk of fracture, one should consider use of the sclerostin inhibitor romosozumab (moderate-certainty evidence) or recombinant human parathyroid hormone (teriparatide) (low-certainty evidence) followed by a bisphosphonate (conditional recommendation).

Dr. Ott said: “If the [fracture] risk is high, then we should start with an anabolic medication for 1-2 years. If the risk is medium, then use a bisphosphonate for up to 5 years, and then stop and monitor the patient for signs that the medicine is wearing off,” based on blood and urine tests.
 

‘We need medicines that will stop bone aging’

Osteopenia is defined by an arbitrary bone density measurement, Dr. Ott explained. “About half of women over 65 will have osteopenia, and by age 85 there are hardly any ‘normal’ women left.”

“We need medicines that will stop bone aging, which might sound impossible, but we should still try,” she continued.

“In the meantime, while waiting on new discoveries,” Dr. Ott said, “I would not use bisphosphonates in patients who did not already have a fracture or whose bone density T-score was better than –2.5 because, in the major study, alendronate did not prevent fractures in this group.”

Many people are worried about bisphosphonates because of problems with the jaw or femur. These are real, but they are very rare during the first 5 years of treatment, Dr. Ott noted. Then the risk starts to rise, up to more than 1 in 1,000 after 8 years. So people can get the benefits of these drugs with very low risk for 5 years.

“An immediate [guideline] update is necessary to address the severity of bone loss and the high risk for vertebral fractures after discontinuation of denosumab,” Dr. Ott urged.

“I don’t agree with using denosumab for osteoporosis as a second-line treatment,” she said. “I would use it only in patients who have cancer or unusually high bone resorption. You have to get a dose strictly every 6 months, and if you need to stop, it is recommended to treat with bisphosphonates. Denosumab is a poor choice for somebody who does not want to take a bisphosphonate. Many patients and even too many doctors do not realize how serious it can be to skip a dose.”

“I also think that men could be treated with anabolic medications,” Dr. Ott said. “Clinical trials show they respond the same as women. Many men have osteoporosis as a consequence of low testosterone, and then they can usually be treated with testosterone. Osteoporosis in men is a serious problem that is too often ignored – almost reverse discrimination.”

It is also unfortunate that the review and recommendations do not address estrogen, one of the most effective medications to prevent osteoporotic fractures, according to Dr. Ott.
 

Clinical considerations in addition to drug types

The new guideline also advises:

• Clinicians treating adults with osteoporosis should encourage adherence to recommended treatments and healthy lifestyle habits, including exercise, and counseling to evaluate and prevent falls.
• All adults with osteopenia or osteoporosis should have adequate calcium and vitamin D intake, as part of fracture prevention.
• Clinicians should assess baseline fracture risk based on bone density, fracture history, fracture risk factors, and response to prior osteoporosis treatments.
• Current evidence suggests that more than 3-5 years of bisphosphonate therapy reduces risk for new vertebral but not other fractures; however, it also increases risk for long-term harms. Therefore, clinicians should consider stopping bisphosphonate treatment after 5 years unless the patient has a strong indication for treatment continuation.
• The decision for a bisphosphonate holiday (temporary discontinuation) and its duration should be based on baseline fracture risk, medication half-life in bone, and benefits and harms.
• Women treated with an anabolic agent who discontinue it should be offered an antiresorptive agent to preserve gains and because of serious risk for rebound and multiple vertebral fractures.
• Adults older than 65 years with osteoporosis may be at increased risk for falls or other adverse events because of drug interactions.
• Transgender persons have variable risk for low bone mass.

The review and guideline were funded by the ACP. Dr. Ott has reported no relevant disclosures. Relevant financial disclosures for other authors are listed with the guideline and review.

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

The American College of Physicians has updated their guideline for pharmacotherapy to reduce fracture risk in adults with primary osteoporosis or osteopenia (low bone mass) based on a systematic review of the evidence.

This is the first update for 5 years since the previous guidance was published in 2017.

It strongly recommends initial therapy with bisphosphonates for postmenopausal women with osteoporosis, as well as men with osteoporosis, among other recommendations.

However, the author of an accompanying editorial, Susan M. Ott, MD, says: “The decision to start a bisphosphonate is actually not that easy.”

She also queries some of the other recommendations in the guidance.

Her editorial, along with the guideline by Amir Qaseem, MD, PhD, MPH, and colleagues, and systematic review by Chelsea Ayers, MPH, and colleagues, were published in the Annals of Internal Medicine.

Ryan D. Mire, MD, MACP, president of the ACP, gave a brief overview of the new guidance in a video.
 

Systematic review

The ACP commissioned a review of the evidence because it says new data have emerged on the efficacy of newer medications for osteoporosis and low bone mass, as well as treatment comparisons, and treatment in men.

The review authors identified 34 randomized controlled trials (in 100 publications) and 36 observational studies, which evaluated the following pharmacologic interventions:

• Antiresorptive drugs: four bisphosphonates (alendronate, ibandronate, risedronate, zoledronate) and a RANK ligand inhibitor (denosumab).
• Anabolic drugs: an analog of human parathyroid hormone (PTH)–related protein (abaloparatide), recombinant human PTH (teriparatide), and a sclerostin inhibitor (romosozumab).
• Estrogen agonists: selective estrogen receptor modulators (bazedoxifene, raloxifene).

The authors focused on effectiveness and harms of active drugs compared with placebo or bisphosphonates.
 

Major changes from 2017 guidelines, some questions

“Though there are many nuanced changes in this [2023 guideline] version, perhaps the major change is the explicit hierarchy of pharmacologic recommendations: bisphosphonates first, then denosumab,” Thomas G. Cooney, MD, senior author of the clinical guideline, explained in an interview.

“Bisphosphonates had the most favorable balance among benefits, harms, patient values and preferences, and cost among the examined drugs in postmenopausal females with primary osteoporosis,” Dr. Cooney, professor of medicine, Oregon Health & Science University, Portland, noted, as is stated in the guideline.

“Denosumab also had a favorable long-term net benefit, but bisphosphonates are much cheaper than other pharmacologic treatments and available in generic formulations,” the document states.

The new guideline suggests use of denosumab as second-line pharmacotherapy in adults who have contraindications to or experience adverse effects with bisphosphonates.

The choice among bisphosphonates (alendronate, risedronate, zoledronic acid) would be based on a patient-centered discussion between physician and patient, addressing costs (often related to insurance), delivery-mode preferences (oral versus intravenous), and “values,” which includes the patient’s priorities, concerns, and expectations regarding their health care, Dr. Cooney explained.

Another update in the new guideline is, “We also clarify the specific, albeit more limited, role of sclerostin inhibitors and recombinant PTH ‘to reduce the risk of fractures only in females with primary osteoporosis with very high-risk of fracture’,” Dr. Cooney noted.

In addition, the guideline now states, “treatment to reduce the risk of fractures in males rather than limiting it to ‘vertebral fracture’ in men,” as in the 2017 guideline.

It also explicitly includes denosumab as second-line therapy for men, Dr. Cooney noted, but as in 2017, the strength of evidence in men remains low.

“Finally, we also clarified that in females over the age of 65 with low bone mass or osteopenia that an individualized approach be taken to treatment (similar to last guideline), but if treatment is initiated, that a bisphosphonate be used (new content),” he said.

The use of estrogen, treatment duration, drug discontinuation, and serial bone mineral density monitoring were not addressed in this guideline, but will likely be evaluated within 2 to 3 years.
 

‘Osteoporosis treatment: Not easy’ – editorial

In her editorial, Dr. Ott writes: “The data about bisphosphonates may seem overwhelmingly positive, leading to strong recommendations for their use to treat osteoporosis, but the decision to start a bisphosphonate is actually not that easy.”

“A strong recommendation should be given only when future studies are unlikely to change it,” continues Dr. Ott, professor of medicine, University of Washington, Seattle.

“Yet, data already suggest that, in patients with serious osteoporosis, treatment should start with anabolic medications because previous treatment with either bisphosphonates or denosumab will prevent the anabolic response of newer medications.”

“Starting with bisphosphonate will change the bone so it will not respond to the newer medicines, and then a patient will lose the chance for getting the best improvement,” Dr. Ott clarified in an email to this news organization.

But, in fact, the new guidance does suggest that, to reduce the risk of fractures in females with primary osteoporosis at very high risk of fracture, one should consider use of the sclerostin inhibitor romosozumab (moderate-certainty evidence) or recombinant human parathyroid hormone (teriparatide) (low-certainty evidence) followed by a bisphosphonate (conditional recommendation).

Dr. Ott said: “If the [fracture] risk is high, then we should start with an anabolic medication for 1-2 years. If the risk is medium, then use a bisphosphonate for up to 5 years, and then stop and monitor the patient for signs that the medicine is wearing off,” based on blood and urine tests.
 

‘We need medicines that will stop bone aging’

Osteopenia is defined by an arbitrary bone density measurement, Dr. Ott explained. “About half of women over 65 will have osteopenia, and by age 85 there are hardly any ‘normal’ women left.”

“We need medicines that will stop bone aging, which might sound impossible, but we should still try,” she continued.

“In the meantime, while waiting on new discoveries,” Dr. Ott said, “I would not use bisphosphonates in patients who did not already have a fracture or whose bone density T-score was better than –2.5 because, in the major study, alendronate did not prevent fractures in this group.”

Many people are worried about bisphosphonates because of problems with the jaw or femur. These are real, but they are very rare during the first 5 years of treatment, Dr. Ott noted. Then the risk starts to rise, up to more than 1 in 1,000 after 8 years. So people can get the benefits of these drugs with very low risk for 5 years.

“An immediate [guideline] update is necessary to address the severity of bone loss and the high risk for vertebral fractures after discontinuation of denosumab,” Dr. Ott urged.

“I don’t agree with using denosumab for osteoporosis as a second-line treatment,” she said. “I would use it only in patients who have cancer or unusually high bone resorption. You have to get a dose strictly every 6 months, and if you need to stop, it is recommended to treat with bisphosphonates. Denosumab is a poor choice for somebody who does not want to take a bisphosphonate. Many patients and even too many doctors do not realize how serious it can be to skip a dose.”

“I also think that men could be treated with anabolic medications,” Dr. Ott said. “Clinical trials show they respond the same as women. Many men have osteoporosis as a consequence of low testosterone, and then they can usually be treated with testosterone. Osteoporosis in men is a serious problem that is too often ignored – almost reverse discrimination.”

It is also unfortunate that the review and recommendations do not address estrogen, one of the most effective medications to prevent osteoporotic fractures, according to Dr. Ott.
 

Clinical considerations in addition to drug types

The new guideline also advises:

• Clinicians treating adults with osteoporosis should encourage adherence to recommended treatments and healthy lifestyle habits, including exercise, and counseling to evaluate and prevent falls.
• All adults with osteopenia or osteoporosis should have adequate calcium and vitamin D intake, as part of fracture prevention.
• Clinicians should assess baseline fracture risk based on bone density, fracture history, fracture risk factors, and response to prior osteoporosis treatments.
• Current evidence suggests that more than 3-5 years of bisphosphonate therapy reduces risk for new vertebral but not other fractures; however, it also increases risk for long-term harms. Therefore, clinicians should consider stopping bisphosphonate treatment after 5 years unless the patient has a strong indication for treatment continuation.
• The decision for a bisphosphonate holiday (temporary discontinuation) and its duration should be based on baseline fracture risk, medication half-life in bone, and benefits and harms.
• Women treated with an anabolic agent who discontinue it should be offered an antiresorptive agent to preserve gains and because of serious risk for rebound and multiple vertebral fractures.
• Adults older than 65 years with osteoporosis may be at increased risk for falls or other adverse events because of drug interactions.
• Transgender persons have variable risk for low bone mass.

The review and guideline were funded by the ACP. Dr. Ott has reported no relevant disclosures. Relevant financial disclosures for other authors are listed with the guideline and review.

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

The American College of Physicians has updated their guideline for pharmacotherapy to reduce fracture risk in adults with primary osteoporosis or osteopenia (low bone mass) based on a systematic review of the evidence.

This is the first update for 5 years since the previous guidance was published in 2017.

It strongly recommends initial therapy with bisphosphonates for postmenopausal women with osteoporosis, as well as men with osteoporosis, among other recommendations.

However, the author of an accompanying editorial, Susan M. Ott, MD, says: “The decision to start a bisphosphonate is actually not that easy.”

She also queries some of the other recommendations in the guidance.

Her editorial, along with the guideline by Amir Qaseem, MD, PhD, MPH, and colleagues, and systematic review by Chelsea Ayers, MPH, and colleagues, were published in the Annals of Internal Medicine.

Ryan D. Mire, MD, MACP, president of the ACP, gave a brief overview of the new guidance in a video.
 

Systematic review

The ACP commissioned a review of the evidence because it says new data have emerged on the efficacy of newer medications for osteoporosis and low bone mass, as well as treatment comparisons, and treatment in men.

The review authors identified 34 randomized controlled trials (in 100 publications) and 36 observational studies, which evaluated the following pharmacologic interventions:

• Antiresorptive drugs: four bisphosphonates (alendronate, ibandronate, risedronate, zoledronate) and a RANK ligand inhibitor (denosumab).
• Anabolic drugs: an analog of human parathyroid hormone (PTH)–related protein (abaloparatide), recombinant human PTH (teriparatide), and a sclerostin inhibitor (romosozumab).
• Estrogen agonists: selective estrogen receptor modulators (bazedoxifene, raloxifene).

The authors focused on effectiveness and harms of active drugs compared with placebo or bisphosphonates.
 

Major changes from 2017 guidelines, some questions

“Though there are many nuanced changes in this [2023 guideline] version, perhaps the major change is the explicit hierarchy of pharmacologic recommendations: bisphosphonates first, then denosumab,” Thomas G. Cooney, MD, senior author of the clinical guideline, explained in an interview.

“Bisphosphonates had the most favorable balance among benefits, harms, patient values and preferences, and cost among the examined drugs in postmenopausal females with primary osteoporosis,” Dr. Cooney, professor of medicine, Oregon Health & Science University, Portland, noted, as is stated in the guideline.

“Denosumab also had a favorable long-term net benefit, but bisphosphonates are much cheaper than other pharmacologic treatments and available in generic formulations,” the document states.

The new guideline suggests use of denosumab as second-line pharmacotherapy in adults who have contraindications to or experience adverse effects with bisphosphonates.

The choice among bisphosphonates (alendronate, risedronate, zoledronic acid) would be based on a patient-centered discussion between physician and patient, addressing costs (often related to insurance), delivery-mode preferences (oral versus intravenous), and “values,” which includes the patient’s priorities, concerns, and expectations regarding their health care, Dr. Cooney explained.

Another update in the new guideline is, “We also clarify the specific, albeit more limited, role of sclerostin inhibitors and recombinant PTH ‘to reduce the risk of fractures only in females with primary osteoporosis with very high-risk of fracture’,” Dr. Cooney noted.

In addition, the guideline now states, “treatment to reduce the risk of fractures in males rather than limiting it to ‘vertebral fracture’ in men,” as in the 2017 guideline.

It also explicitly includes denosumab as second-line therapy for men, Dr. Cooney noted, but as in 2017, the strength of evidence in men remains low.

“Finally, we also clarified that in females over the age of 65 with low bone mass or osteopenia that an individualized approach be taken to treatment (similar to last guideline), but if treatment is initiated, that a bisphosphonate be used (new content),” he said.

The use of estrogen, treatment duration, drug discontinuation, and serial bone mineral density monitoring were not addressed in this guideline, but will likely be evaluated within 2 to 3 years.
 

‘Osteoporosis treatment: Not easy’ – editorial

In her editorial, Dr. Ott writes: “The data about bisphosphonates may seem overwhelmingly positive, leading to strong recommendations for their use to treat osteoporosis, but the decision to start a bisphosphonate is actually not that easy.”

“A strong recommendation should be given only when future studies are unlikely to change it,” continues Dr. Ott, professor of medicine, University of Washington, Seattle.

“Yet, data already suggest that, in patients with serious osteoporosis, treatment should start with anabolic medications because previous treatment with either bisphosphonates or denosumab will prevent the anabolic response of newer medications.”

“Starting with bisphosphonate will change the bone so it will not respond to the newer medicines, and then a patient will lose the chance for getting the best improvement,” Dr. Ott clarified in an email to this news organization.

But, in fact, the new guidance does suggest that, to reduce the risk of fractures in females with primary osteoporosis at very high risk of fracture, one should consider use of the sclerostin inhibitor romosozumab (moderate-certainty evidence) or recombinant human parathyroid hormone (teriparatide) (low-certainty evidence) followed by a bisphosphonate (conditional recommendation).

Dr. Ott said: “If the [fracture] risk is high, then we should start with an anabolic medication for 1-2 years. If the risk is medium, then use a bisphosphonate for up to 5 years, and then stop and monitor the patient for signs that the medicine is wearing off,” based on blood and urine tests.
 

‘We need medicines that will stop bone aging’

Osteopenia is defined by an arbitrary bone density measurement, Dr. Ott explained. “About half of women over 65 will have osteopenia, and by age 85 there are hardly any ‘normal’ women left.”

“We need medicines that will stop bone aging, which might sound impossible, but we should still try,” she continued.

“In the meantime, while waiting on new discoveries,” Dr. Ott said, “I would not use bisphosphonates in patients who did not already have a fracture or whose bone density T-score was better than –2.5 because, in the major study, alendronate did not prevent fractures in this group.”

Many people are worried about bisphosphonates because of problems with the jaw or femur. These are real, but they are very rare during the first 5 years of treatment, Dr. Ott noted. Then the risk starts to rise, up to more than 1 in 1,000 after 8 years. So people can get the benefits of these drugs with very low risk for 5 years.

“An immediate [guideline] update is necessary to address the severity of bone loss and the high risk for vertebral fractures after discontinuation of denosumab,” Dr. Ott urged.

“I don’t agree with using denosumab for osteoporosis as a second-line treatment,” she said. “I would use it only in patients who have cancer or unusually high bone resorption. You have to get a dose strictly every 6 months, and if you need to stop, it is recommended to treat with bisphosphonates. Denosumab is a poor choice for somebody who does not want to take a bisphosphonate. Many patients and even too many doctors do not realize how serious it can be to skip a dose.”

“I also think that men could be treated with anabolic medications,” Dr. Ott said. “Clinical trials show they respond the same as women. Many men have osteoporosis as a consequence of low testosterone, and then they can usually be treated with testosterone. Osteoporosis in men is a serious problem that is too often ignored – almost reverse discrimination.”

It is also unfortunate that the review and recommendations do not address estrogen, one of the most effective medications to prevent osteoporotic fractures, according to Dr. Ott.
 

Clinical considerations in addition to drug types

The new guideline also advises:

• Clinicians treating adults with osteoporosis should encourage adherence to recommended treatments and healthy lifestyle habits, including exercise, and counseling to evaluate and prevent falls.
• All adults with osteopenia or osteoporosis should have adequate calcium and vitamin D intake, as part of fracture prevention.
• Clinicians should assess baseline fracture risk based on bone density, fracture history, fracture risk factors, and response to prior osteoporosis treatments.
• Current evidence suggests that more than 3-5 years of bisphosphonate therapy reduces risk for new vertebral but not other fractures; however, it also increases risk for long-term harms. Therefore, clinicians should consider stopping bisphosphonate treatment after 5 years unless the patient has a strong indication for treatment continuation.
• The decision for a bisphosphonate holiday (temporary discontinuation) and its duration should be based on baseline fracture risk, medication half-life in bone, and benefits and harms.
• Women treated with an anabolic agent who discontinue it should be offered an antiresorptive agent to preserve gains and because of serious risk for rebound and multiple vertebral fractures.
• Adults older than 65 years with osteoporosis may be at increased risk for falls or other adverse events because of drug interactions.
• Transgender persons have variable risk for low bone mass.

The review and guideline were funded by the ACP. Dr. Ott has reported no relevant disclosures. Relevant financial disclosures for other authors are listed with the guideline and review.

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