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Limiting antibiotic overprescription in pandemics: New guidelines
A statement by the Society for Healthcare Epidemiology of America, published online in Infection Control & Hospital Epidemiology, offers health care providers guidelines on how to prevent inappropriate antibiotic use in future pandemics and to avoid some of the negative scenarios that have been seen with COVID-19.
According to the U.S. Centers of Disease Control and Prevention,
The culprit might be the widespread antibiotic overprescription during the current pandemic. A 2022 meta-analysis revealed that in high-income countries, 58% of patients with COVID-19 were given antibiotics, whereas in lower- and middle-income countries, 89% of patients were put on such drugs. Some hospitals in Europe and the United States reported similarly elevated numbers, sometimes approaching 100%.
“We’ve lost control,” Natasha Pettit, PharmD, pharmacy director at University of Chicago Medicine, told this news organization. Dr. Pettit was not involved in the SHEA study. “Even if CDC didn’t come out with that data, I can tell you right now more of my time is spent trying to figure out how to manage these multi-drug–resistant infections, and we are running out of options for these patients,”
“Dealing with uncertainty, exhaustion, [and] critical illness in often young, otherwise healthy patients meant doctors wanted to do something for their patients,” said Tamar Barlam, MD, an infectious diseases expert at the Boston Medical Center who led the development of the SHEA white paper, in an interview.
That something often was a prescription for antibiotics, even without a clear indication that they were actually needed. A British study revealed that in times of pandemic uncertainty, clinicians often reached for antibiotics “just in case” and referred to conservative prescribing as “bravery.”
Studies have shown, however, that bacterial co-infections in COVID-19 are rare. A 2020 meta-analysis of 24 studies concluded that only 3.5% of patients had a bacterial co-infection on presentation, and 14.3% had a secondary infection. Similar patterns had previously been observed in other viral outbreaks. Research on MERS-CoV, for example, documented only 1% of patients with a bacterial co-infection on admission. During the 2009 H1N1 influenza pandemic, that number was 12% of non–ICU hospitalized patients.
Yet, according to Dr. Pettit, even when such data became available, it didn’t necessarily change prescribing patterns. “Information was coming at us so quickly, I think the providers didn’t have a moment to see the data, to understand what it meant for their prescribing. Having external guidance earlier on would have been hugely helpful,” she told this news organization.
That’s where the newly published SHEA statement comes in: It outlines recommendations on when to prescribe antibiotics during a respiratory viral pandemic, what tests to order, and when to de-escalate or discontinue the treatment. These recommendations include, for instance, advice to not trust inflammatory markers as reliable indicators of bacterial or fungal infection and to not use procalcitonin routinely to aid in the decision to initiate antibiotics.
According to Dr. Barlam, one of the crucial lessons here is that if clinicians see patients with symptoms that are consistent with the current pandemic, they should trust their own impressions and avoid reaching for antimicrobials “just in case.”
Another important lesson is that antibiotic stewardship programs have a huge role to play during pandemics. They should not only monitor prescribing but also compile new information on bacterial co-infections as it gets released and make sure it reaches the clinicians in a clear form.
Evidence suggests that such programs and guidelines do work to limit unnecessary antibiotic use. In one medical center in Chicago, for example, before recommendations on when to initiate and discontinue antimicrobials were released, over 74% of COVID-19 patients received antibiotics. After guidelines were put in place, the use of such drugs fell to 42%.
Dr. Pettit believes, however, that it’s important not to leave each medical center to its own devices. “Hindsight is always twenty-twenty,” she said, “but I think it would be great that, if we start hearing about a pathogen that might lead to another pandemic, we should have a mechanism in place to call together an expert body to get guidance for how antimicrobial stewardship programs should get involved.”
One of the authors of the SHEA statement, Susan Seo, reports an investigator-initiated Merck grant on cost-effectiveness of letermovir in hematopoietic stem cell transplant patients. Another author, Graeme Forrest, reports a clinical study grant from Regeneron for inpatient monoclonals against SARS-CoV-2. All other authors report no conflicts of interest. The study was independently supported.
A version of this article first appeared on Medscape.com.
A statement by the Society for Healthcare Epidemiology of America, published online in Infection Control & Hospital Epidemiology, offers health care providers guidelines on how to prevent inappropriate antibiotic use in future pandemics and to avoid some of the negative scenarios that have been seen with COVID-19.
According to the U.S. Centers of Disease Control and Prevention,
The culprit might be the widespread antibiotic overprescription during the current pandemic. A 2022 meta-analysis revealed that in high-income countries, 58% of patients with COVID-19 were given antibiotics, whereas in lower- and middle-income countries, 89% of patients were put on such drugs. Some hospitals in Europe and the United States reported similarly elevated numbers, sometimes approaching 100%.
“We’ve lost control,” Natasha Pettit, PharmD, pharmacy director at University of Chicago Medicine, told this news organization. Dr. Pettit was not involved in the SHEA study. “Even if CDC didn’t come out with that data, I can tell you right now more of my time is spent trying to figure out how to manage these multi-drug–resistant infections, and we are running out of options for these patients,”
“Dealing with uncertainty, exhaustion, [and] critical illness in often young, otherwise healthy patients meant doctors wanted to do something for their patients,” said Tamar Barlam, MD, an infectious diseases expert at the Boston Medical Center who led the development of the SHEA white paper, in an interview.
That something often was a prescription for antibiotics, even without a clear indication that they were actually needed. A British study revealed that in times of pandemic uncertainty, clinicians often reached for antibiotics “just in case” and referred to conservative prescribing as “bravery.”
Studies have shown, however, that bacterial co-infections in COVID-19 are rare. A 2020 meta-analysis of 24 studies concluded that only 3.5% of patients had a bacterial co-infection on presentation, and 14.3% had a secondary infection. Similar patterns had previously been observed in other viral outbreaks. Research on MERS-CoV, for example, documented only 1% of patients with a bacterial co-infection on admission. During the 2009 H1N1 influenza pandemic, that number was 12% of non–ICU hospitalized patients.
Yet, according to Dr. Pettit, even when such data became available, it didn’t necessarily change prescribing patterns. “Information was coming at us so quickly, I think the providers didn’t have a moment to see the data, to understand what it meant for their prescribing. Having external guidance earlier on would have been hugely helpful,” she told this news organization.
That’s where the newly published SHEA statement comes in: It outlines recommendations on when to prescribe antibiotics during a respiratory viral pandemic, what tests to order, and when to de-escalate or discontinue the treatment. These recommendations include, for instance, advice to not trust inflammatory markers as reliable indicators of bacterial or fungal infection and to not use procalcitonin routinely to aid in the decision to initiate antibiotics.
According to Dr. Barlam, one of the crucial lessons here is that if clinicians see patients with symptoms that are consistent with the current pandemic, they should trust their own impressions and avoid reaching for antimicrobials “just in case.”
Another important lesson is that antibiotic stewardship programs have a huge role to play during pandemics. They should not only monitor prescribing but also compile new information on bacterial co-infections as it gets released and make sure it reaches the clinicians in a clear form.
Evidence suggests that such programs and guidelines do work to limit unnecessary antibiotic use. In one medical center in Chicago, for example, before recommendations on when to initiate and discontinue antimicrobials were released, over 74% of COVID-19 patients received antibiotics. After guidelines were put in place, the use of such drugs fell to 42%.
Dr. Pettit believes, however, that it’s important not to leave each medical center to its own devices. “Hindsight is always twenty-twenty,” she said, “but I think it would be great that, if we start hearing about a pathogen that might lead to another pandemic, we should have a mechanism in place to call together an expert body to get guidance for how antimicrobial stewardship programs should get involved.”
One of the authors of the SHEA statement, Susan Seo, reports an investigator-initiated Merck grant on cost-effectiveness of letermovir in hematopoietic stem cell transplant patients. Another author, Graeme Forrest, reports a clinical study grant from Regeneron for inpatient monoclonals against SARS-CoV-2. All other authors report no conflicts of interest. The study was independently supported.
A version of this article first appeared on Medscape.com.
A statement by the Society for Healthcare Epidemiology of America, published online in Infection Control & Hospital Epidemiology, offers health care providers guidelines on how to prevent inappropriate antibiotic use in future pandemics and to avoid some of the negative scenarios that have been seen with COVID-19.
According to the U.S. Centers of Disease Control and Prevention,
The culprit might be the widespread antibiotic overprescription during the current pandemic. A 2022 meta-analysis revealed that in high-income countries, 58% of patients with COVID-19 were given antibiotics, whereas in lower- and middle-income countries, 89% of patients were put on such drugs. Some hospitals in Europe and the United States reported similarly elevated numbers, sometimes approaching 100%.
“We’ve lost control,” Natasha Pettit, PharmD, pharmacy director at University of Chicago Medicine, told this news organization. Dr. Pettit was not involved in the SHEA study. “Even if CDC didn’t come out with that data, I can tell you right now more of my time is spent trying to figure out how to manage these multi-drug–resistant infections, and we are running out of options for these patients,”
“Dealing with uncertainty, exhaustion, [and] critical illness in often young, otherwise healthy patients meant doctors wanted to do something for their patients,” said Tamar Barlam, MD, an infectious diseases expert at the Boston Medical Center who led the development of the SHEA white paper, in an interview.
That something often was a prescription for antibiotics, even without a clear indication that they were actually needed. A British study revealed that in times of pandemic uncertainty, clinicians often reached for antibiotics “just in case” and referred to conservative prescribing as “bravery.”
Studies have shown, however, that bacterial co-infections in COVID-19 are rare. A 2020 meta-analysis of 24 studies concluded that only 3.5% of patients had a bacterial co-infection on presentation, and 14.3% had a secondary infection. Similar patterns had previously been observed in other viral outbreaks. Research on MERS-CoV, for example, documented only 1% of patients with a bacterial co-infection on admission. During the 2009 H1N1 influenza pandemic, that number was 12% of non–ICU hospitalized patients.
Yet, according to Dr. Pettit, even when such data became available, it didn’t necessarily change prescribing patterns. “Information was coming at us so quickly, I think the providers didn’t have a moment to see the data, to understand what it meant for their prescribing. Having external guidance earlier on would have been hugely helpful,” she told this news organization.
That’s where the newly published SHEA statement comes in: It outlines recommendations on when to prescribe antibiotics during a respiratory viral pandemic, what tests to order, and when to de-escalate or discontinue the treatment. These recommendations include, for instance, advice to not trust inflammatory markers as reliable indicators of bacterial or fungal infection and to not use procalcitonin routinely to aid in the decision to initiate antibiotics.
According to Dr. Barlam, one of the crucial lessons here is that if clinicians see patients with symptoms that are consistent with the current pandemic, they should trust their own impressions and avoid reaching for antimicrobials “just in case.”
Another important lesson is that antibiotic stewardship programs have a huge role to play during pandemics. They should not only monitor prescribing but also compile new information on bacterial co-infections as it gets released and make sure it reaches the clinicians in a clear form.
Evidence suggests that such programs and guidelines do work to limit unnecessary antibiotic use. In one medical center in Chicago, for example, before recommendations on when to initiate and discontinue antimicrobials were released, over 74% of COVID-19 patients received antibiotics. After guidelines were put in place, the use of such drugs fell to 42%.
Dr. Pettit believes, however, that it’s important not to leave each medical center to its own devices. “Hindsight is always twenty-twenty,” she said, “but I think it would be great that, if we start hearing about a pathogen that might lead to another pandemic, we should have a mechanism in place to call together an expert body to get guidance for how antimicrobial stewardship programs should get involved.”
One of the authors of the SHEA statement, Susan Seo, reports an investigator-initiated Merck grant on cost-effectiveness of letermovir in hematopoietic stem cell transplant patients. Another author, Graeme Forrest, reports a clinical study grant from Regeneron for inpatient monoclonals against SARS-CoV-2. All other authors report no conflicts of interest. The study was independently supported.
A version of this article first appeared on Medscape.com.
FROM INFECTION CONTROL & HOSPITAL EPIDEMIOLOGY
Genetic tests create treatment opportunities and confusion for breast cancer patients
The past decade has witnessed a rapid expansion of genetic tests, including new instruments to inform patients who have been diagnosed with breast cancer about the risk of recurrence and to guide their treatment.
Patients are sometimes left paying out-of-pocket for exams that are not yet the standard of care, and even the most up-to-date oncologists may be uncertain how to incorporate the flood of new information into what used to be standard treatment protocols.
A quarter-century ago, Myriad Genetics introduced the first breast cancer genetic test for BRCA mutations, two genes associated with a substantially elevated risk of getting breast cancer, opening the door to a new era in genetic testing. BRCA1 and BRCA2 mutations account for as many as half of all hereditary breast cancers, and people with a problematic mutation on one of those genes have a 45%-72% chance of developing breast cancer during their lifetimes. They may also be at higher risk for ovarian and other cancers than people without harmful BRCA mutations.
But the clinical significance is murkier for many other genetic tests.
Testing for BRCA1 and BRCA2 genes used to cost thousands of dollars. Now, for a fraction of that, doctors can order multigene test panels from commercial labs that look for mutations in dozens of genes. Some direct-to-consumer companies offer screening panels for a few hundred dollars, though their reliability varies.
When Jen Carbary was diagnosed with breast cancer in 2017 at age 44, genetic testing identified a mutation in a gene called PALB2 that significantly increases the risk of developing breast cancer. Guidelines suggest that breast cancer patients with a PALB2 mutation, much like those with BRCA1 and BRCA2 mutations, consider having a mastectomy to reduce the chance of a breast cancer recurrence.
“I wish genetic testing was the standard of care,” said Ms. Carbary, who owed nothing for the test because her insurer covered the cost.
Ms. Carbary, who lives in Sterling Heights, Mich., said the test results affirmed the decision she had already made to have a double mastectomy and provided important information for family members, including her 21-year-old daughter and 18-year-old son, who will likely be tested in their mid-20s or early 30s.
But some breast cancer experts are concerned that widespread testing may also identify genetic mutations whose impact is unclear, creating anxiety and leading to further testing and to treatment of questionable value that could raise costs for the health care system.
It can also confuse patients.
“It happens a lot, that patients find their way to us after getting confusing results elsewhere,” said Mark Robson, MD, chief of the breast medicine service at Memorial Sloan Kettering Cancer Center, New York. Robson said the cancer center has a clinical genetics service, staffed by doctors and genetic counselors, that helps people make decisions about how to manage genetic testing results.
For people diagnosed with breast cancer, many professional groups, including the influential National Comprehensive Cancer Network, recommend limiting testing to certain people, including those with high-risk factors, such as a family history of breast cancer; those who are 45 or younger when they’re diagnosed; and those with Ashkenazi Jewish ancestry.
But in 2019, the American Society of Breast Surgeons recommended a different approach: Offer genetic testing to all patients who are diagnosed with or have a personal history of breast cancer. The recommendation was controversial.
“The NCCN guidelines [cover] most of the women who needed testing, but we wanted to get them all,” said Eric Manahan, MD, a general surgeon in Dalton, Georgia, and a member of the surgeons group’s board of directors.
Mutations on other genes that are associated with breast cancer are much less common than BRCA1 and BRCA2 mutations and generally don’t increase the risk of developing breast cancer as much. The cancer-causing impact of these genes may be less clear than that of the BRCA genes, which have been tested for since the mid-1990s.
And the appropriate response to the less common mutations – whether to consider a risk-reducing mastectomy or stepped-up screening – is often unclear.
“Things get sloppier and sloppier when you look at other genes,” said Steven Katz, MD, MPH, a professor of medicine and health management and policy at the University of Michigan. “The risks tend to be lower for different cancers, and less certain and more variable. You might walk away wondering: ‘Why’d I have to know that?’ ”
After people are diagnosed with breast cancer, genetic testing can help inform their decisions about the types of surgery to pursue – for example, a high risk of recurrence or a new breast cancer might persuade some to opt for more extensive surgery, such as a double mastectomy. Testing can also provide important information to family members about their potential cancer risk.
(This type of “germline” genetic testing, as it’s called, looks at mutations in the genes that people inherit from their parents. It is different from genomic tumor tests that look at specific genes or proteins in the cancer cells and can help doctors understand the rate at which the cancer cells are dividing, for example, and the likelihood of a cancer recurrence.)
Increasingly, germline genetic testing can also help guide other treatment decisions. Some patients with metastatic breast cancer who have BRCA1 or BRCA2 mutations may be good candidates for poly (ADP-ribose) polymerase inhibitors, cancer drugs that target tumors with mutations in those genes.
But genetic testing that uncovers inherited mutations in many other genes yields less clearly actionable information, even though positive results may alarm people.
At Memorial Sloan Kettering, cancer specialists focus on “therapeutic actionability,” said Dr. Robson. Will testing help someone decide whether she should get a double mastectomy or provide other important guidance? “A policy of testing everyone will identify very few additional BRCA breast mutations but will cost a lot.”
As a result, doctors are debating how best to deploy and incorporate new genetic knowledge. Insurers are trying to figure out which to pay for.
There is both underuse of tests that science says are relevant and overuse of tests that experts say provide information that can’t be interpreted with any scientific certainty.
The result may be confusion for patients newly diagnosed with breast cancer as they confront the expense of genetic tests and sometimes little guidance on the proper treatment.
Some doctors say the first step is to make sure that the small group of people who would clearly benefit are getting the genetic tests whose meaning is clearly understood. Only 15% of breast cancer patients who met select NCCN testing guidelines for inherited cancer received genetic testing, according to a 2017 study that examined data from a national household health survey between 2005 and 2015.
“I would argue that our focus needs to be on the people who are at high risk for breast cancer that aren’t even identified yet,” said Tuya Pal, MD, associate director for cancer health disparities at Vanderbilt-Ingram Cancer Center and vice chair of the NCCN guidelines panel for genetic/familial high-risk assessment of breast, ovarian, and pancreatic cancers.
Patients may fall through the cracks because no one tells them they should be tested. In one analysis, 56% of high-risk breast cancer patients who didn’t get genetic testing said their doctors didn’t recommend it.
Even if doctors recommend genetic testing, they may lack the expertise to determine which tests people need and how to interpret the results. That’s the role of genetic counselors, but their ranks are stretched thin.
The consequences can be serious. In a study of 666 breast cancer patients who received genetic testing, half of those at average risk for inherited cancer got double mastectomies based on test results that found “variants of uncertain significance,” which aren’t clinically actionable. As many as half of surgeons reported managing such patients the same way as those with cancer-causing mutations.
“The bulk of our research would say that there is still room for improvement in terms of clinicians getting the understanding they need,” said Allison Kurian, MD, director of the women’s clinical cancer genetics program at Stanford (Calif.) University and a coauthor of the study.
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
The past decade has witnessed a rapid expansion of genetic tests, including new instruments to inform patients who have been diagnosed with breast cancer about the risk of recurrence and to guide their treatment.
Patients are sometimes left paying out-of-pocket for exams that are not yet the standard of care, and even the most up-to-date oncologists may be uncertain how to incorporate the flood of new information into what used to be standard treatment protocols.
A quarter-century ago, Myriad Genetics introduced the first breast cancer genetic test for BRCA mutations, two genes associated with a substantially elevated risk of getting breast cancer, opening the door to a new era in genetic testing. BRCA1 and BRCA2 mutations account for as many as half of all hereditary breast cancers, and people with a problematic mutation on one of those genes have a 45%-72% chance of developing breast cancer during their lifetimes. They may also be at higher risk for ovarian and other cancers than people without harmful BRCA mutations.
But the clinical significance is murkier for many other genetic tests.
Testing for BRCA1 and BRCA2 genes used to cost thousands of dollars. Now, for a fraction of that, doctors can order multigene test panels from commercial labs that look for mutations in dozens of genes. Some direct-to-consumer companies offer screening panels for a few hundred dollars, though their reliability varies.
When Jen Carbary was diagnosed with breast cancer in 2017 at age 44, genetic testing identified a mutation in a gene called PALB2 that significantly increases the risk of developing breast cancer. Guidelines suggest that breast cancer patients with a PALB2 mutation, much like those with BRCA1 and BRCA2 mutations, consider having a mastectomy to reduce the chance of a breast cancer recurrence.
“I wish genetic testing was the standard of care,” said Ms. Carbary, who owed nothing for the test because her insurer covered the cost.
Ms. Carbary, who lives in Sterling Heights, Mich., said the test results affirmed the decision she had already made to have a double mastectomy and provided important information for family members, including her 21-year-old daughter and 18-year-old son, who will likely be tested in their mid-20s or early 30s.
But some breast cancer experts are concerned that widespread testing may also identify genetic mutations whose impact is unclear, creating anxiety and leading to further testing and to treatment of questionable value that could raise costs for the health care system.
It can also confuse patients.
“It happens a lot, that patients find their way to us after getting confusing results elsewhere,” said Mark Robson, MD, chief of the breast medicine service at Memorial Sloan Kettering Cancer Center, New York. Robson said the cancer center has a clinical genetics service, staffed by doctors and genetic counselors, that helps people make decisions about how to manage genetic testing results.
For people diagnosed with breast cancer, many professional groups, including the influential National Comprehensive Cancer Network, recommend limiting testing to certain people, including those with high-risk factors, such as a family history of breast cancer; those who are 45 or younger when they’re diagnosed; and those with Ashkenazi Jewish ancestry.
But in 2019, the American Society of Breast Surgeons recommended a different approach: Offer genetic testing to all patients who are diagnosed with or have a personal history of breast cancer. The recommendation was controversial.
“The NCCN guidelines [cover] most of the women who needed testing, but we wanted to get them all,” said Eric Manahan, MD, a general surgeon in Dalton, Georgia, and a member of the surgeons group’s board of directors.
Mutations on other genes that are associated with breast cancer are much less common than BRCA1 and BRCA2 mutations and generally don’t increase the risk of developing breast cancer as much. The cancer-causing impact of these genes may be less clear than that of the BRCA genes, which have been tested for since the mid-1990s.
And the appropriate response to the less common mutations – whether to consider a risk-reducing mastectomy or stepped-up screening – is often unclear.
“Things get sloppier and sloppier when you look at other genes,” said Steven Katz, MD, MPH, a professor of medicine and health management and policy at the University of Michigan. “The risks tend to be lower for different cancers, and less certain and more variable. You might walk away wondering: ‘Why’d I have to know that?’ ”
After people are diagnosed with breast cancer, genetic testing can help inform their decisions about the types of surgery to pursue – for example, a high risk of recurrence or a new breast cancer might persuade some to opt for more extensive surgery, such as a double mastectomy. Testing can also provide important information to family members about their potential cancer risk.
(This type of “germline” genetic testing, as it’s called, looks at mutations in the genes that people inherit from their parents. It is different from genomic tumor tests that look at specific genes or proteins in the cancer cells and can help doctors understand the rate at which the cancer cells are dividing, for example, and the likelihood of a cancer recurrence.)
Increasingly, germline genetic testing can also help guide other treatment decisions. Some patients with metastatic breast cancer who have BRCA1 or BRCA2 mutations may be good candidates for poly (ADP-ribose) polymerase inhibitors, cancer drugs that target tumors with mutations in those genes.
But genetic testing that uncovers inherited mutations in many other genes yields less clearly actionable information, even though positive results may alarm people.
At Memorial Sloan Kettering, cancer specialists focus on “therapeutic actionability,” said Dr. Robson. Will testing help someone decide whether she should get a double mastectomy or provide other important guidance? “A policy of testing everyone will identify very few additional BRCA breast mutations but will cost a lot.”
As a result, doctors are debating how best to deploy and incorporate new genetic knowledge. Insurers are trying to figure out which to pay for.
There is both underuse of tests that science says are relevant and overuse of tests that experts say provide information that can’t be interpreted with any scientific certainty.
The result may be confusion for patients newly diagnosed with breast cancer as they confront the expense of genetic tests and sometimes little guidance on the proper treatment.
Some doctors say the first step is to make sure that the small group of people who would clearly benefit are getting the genetic tests whose meaning is clearly understood. Only 15% of breast cancer patients who met select NCCN testing guidelines for inherited cancer received genetic testing, according to a 2017 study that examined data from a national household health survey between 2005 and 2015.
“I would argue that our focus needs to be on the people who are at high risk for breast cancer that aren’t even identified yet,” said Tuya Pal, MD, associate director for cancer health disparities at Vanderbilt-Ingram Cancer Center and vice chair of the NCCN guidelines panel for genetic/familial high-risk assessment of breast, ovarian, and pancreatic cancers.
Patients may fall through the cracks because no one tells them they should be tested. In one analysis, 56% of high-risk breast cancer patients who didn’t get genetic testing said their doctors didn’t recommend it.
Even if doctors recommend genetic testing, they may lack the expertise to determine which tests people need and how to interpret the results. That’s the role of genetic counselors, but their ranks are stretched thin.
The consequences can be serious. In a study of 666 breast cancer patients who received genetic testing, half of those at average risk for inherited cancer got double mastectomies based on test results that found “variants of uncertain significance,” which aren’t clinically actionable. As many as half of surgeons reported managing such patients the same way as those with cancer-causing mutations.
“The bulk of our research would say that there is still room for improvement in terms of clinicians getting the understanding they need,” said Allison Kurian, MD, director of the women’s clinical cancer genetics program at Stanford (Calif.) University and a coauthor of the study.
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
The past decade has witnessed a rapid expansion of genetic tests, including new instruments to inform patients who have been diagnosed with breast cancer about the risk of recurrence and to guide their treatment.
Patients are sometimes left paying out-of-pocket for exams that are not yet the standard of care, and even the most up-to-date oncologists may be uncertain how to incorporate the flood of new information into what used to be standard treatment protocols.
A quarter-century ago, Myriad Genetics introduced the first breast cancer genetic test for BRCA mutations, two genes associated with a substantially elevated risk of getting breast cancer, opening the door to a new era in genetic testing. BRCA1 and BRCA2 mutations account for as many as half of all hereditary breast cancers, and people with a problematic mutation on one of those genes have a 45%-72% chance of developing breast cancer during their lifetimes. They may also be at higher risk for ovarian and other cancers than people without harmful BRCA mutations.
But the clinical significance is murkier for many other genetic tests.
Testing for BRCA1 and BRCA2 genes used to cost thousands of dollars. Now, for a fraction of that, doctors can order multigene test panels from commercial labs that look for mutations in dozens of genes. Some direct-to-consumer companies offer screening panels for a few hundred dollars, though their reliability varies.
When Jen Carbary was diagnosed with breast cancer in 2017 at age 44, genetic testing identified a mutation in a gene called PALB2 that significantly increases the risk of developing breast cancer. Guidelines suggest that breast cancer patients with a PALB2 mutation, much like those with BRCA1 and BRCA2 mutations, consider having a mastectomy to reduce the chance of a breast cancer recurrence.
“I wish genetic testing was the standard of care,” said Ms. Carbary, who owed nothing for the test because her insurer covered the cost.
Ms. Carbary, who lives in Sterling Heights, Mich., said the test results affirmed the decision she had already made to have a double mastectomy and provided important information for family members, including her 21-year-old daughter and 18-year-old son, who will likely be tested in their mid-20s or early 30s.
But some breast cancer experts are concerned that widespread testing may also identify genetic mutations whose impact is unclear, creating anxiety and leading to further testing and to treatment of questionable value that could raise costs for the health care system.
It can also confuse patients.
“It happens a lot, that patients find their way to us after getting confusing results elsewhere,” said Mark Robson, MD, chief of the breast medicine service at Memorial Sloan Kettering Cancer Center, New York. Robson said the cancer center has a clinical genetics service, staffed by doctors and genetic counselors, that helps people make decisions about how to manage genetic testing results.
For people diagnosed with breast cancer, many professional groups, including the influential National Comprehensive Cancer Network, recommend limiting testing to certain people, including those with high-risk factors, such as a family history of breast cancer; those who are 45 or younger when they’re diagnosed; and those with Ashkenazi Jewish ancestry.
But in 2019, the American Society of Breast Surgeons recommended a different approach: Offer genetic testing to all patients who are diagnosed with or have a personal history of breast cancer. The recommendation was controversial.
“The NCCN guidelines [cover] most of the women who needed testing, but we wanted to get them all,” said Eric Manahan, MD, a general surgeon in Dalton, Georgia, and a member of the surgeons group’s board of directors.
Mutations on other genes that are associated with breast cancer are much less common than BRCA1 and BRCA2 mutations and generally don’t increase the risk of developing breast cancer as much. The cancer-causing impact of these genes may be less clear than that of the BRCA genes, which have been tested for since the mid-1990s.
And the appropriate response to the less common mutations – whether to consider a risk-reducing mastectomy or stepped-up screening – is often unclear.
“Things get sloppier and sloppier when you look at other genes,” said Steven Katz, MD, MPH, a professor of medicine and health management and policy at the University of Michigan. “The risks tend to be lower for different cancers, and less certain and more variable. You might walk away wondering: ‘Why’d I have to know that?’ ”
After people are diagnosed with breast cancer, genetic testing can help inform their decisions about the types of surgery to pursue – for example, a high risk of recurrence or a new breast cancer might persuade some to opt for more extensive surgery, such as a double mastectomy. Testing can also provide important information to family members about their potential cancer risk.
(This type of “germline” genetic testing, as it’s called, looks at mutations in the genes that people inherit from their parents. It is different from genomic tumor tests that look at specific genes or proteins in the cancer cells and can help doctors understand the rate at which the cancer cells are dividing, for example, and the likelihood of a cancer recurrence.)
Increasingly, germline genetic testing can also help guide other treatment decisions. Some patients with metastatic breast cancer who have BRCA1 or BRCA2 mutations may be good candidates for poly (ADP-ribose) polymerase inhibitors, cancer drugs that target tumors with mutations in those genes.
But genetic testing that uncovers inherited mutations in many other genes yields less clearly actionable information, even though positive results may alarm people.
At Memorial Sloan Kettering, cancer specialists focus on “therapeutic actionability,” said Dr. Robson. Will testing help someone decide whether she should get a double mastectomy or provide other important guidance? “A policy of testing everyone will identify very few additional BRCA breast mutations but will cost a lot.”
As a result, doctors are debating how best to deploy and incorporate new genetic knowledge. Insurers are trying to figure out which to pay for.
There is both underuse of tests that science says are relevant and overuse of tests that experts say provide information that can’t be interpreted with any scientific certainty.
The result may be confusion for patients newly diagnosed with breast cancer as they confront the expense of genetic tests and sometimes little guidance on the proper treatment.
Some doctors say the first step is to make sure that the small group of people who would clearly benefit are getting the genetic tests whose meaning is clearly understood. Only 15% of breast cancer patients who met select NCCN testing guidelines for inherited cancer received genetic testing, according to a 2017 study that examined data from a national household health survey between 2005 and 2015.
“I would argue that our focus needs to be on the people who are at high risk for breast cancer that aren’t even identified yet,” said Tuya Pal, MD, associate director for cancer health disparities at Vanderbilt-Ingram Cancer Center and vice chair of the NCCN guidelines panel for genetic/familial high-risk assessment of breast, ovarian, and pancreatic cancers.
Patients may fall through the cracks because no one tells them they should be tested. In one analysis, 56% of high-risk breast cancer patients who didn’t get genetic testing said their doctors didn’t recommend it.
Even if doctors recommend genetic testing, they may lack the expertise to determine which tests people need and how to interpret the results. That’s the role of genetic counselors, but their ranks are stretched thin.
The consequences can be serious. In a study of 666 breast cancer patients who received genetic testing, half of those at average risk for inherited cancer got double mastectomies based on test results that found “variants of uncertain significance,” which aren’t clinically actionable. As many as half of surgeons reported managing such patients the same way as those with cancer-causing mutations.
“The bulk of our research would say that there is still room for improvement in terms of clinicians getting the understanding they need,” said Allison Kurian, MD, director of the women’s clinical cancer genetics program at Stanford (Calif.) University and a coauthor of the study.
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
Ketamine linked to reduced suicidal thoughts, depression, anxiety
, new research suggests.
Results from a retrospective chart review analysis, which included more than 400 participants with TRD, illustrate that ketamine is a safe and rapid treatment in a real-world patient population, lead author Patrick A. Oliver, MD, founder and medical director, MindPeace Clinics, Richmond, Va., told this news organization.
The effect was perhaps most notable for reducing suicidal ideation, he said.
“In 2 weeks, we can take somebody from being suicidal to nonsuicidal. It’s a total game changer,” Dr. Oliver added.
Every year in the United States, about 12 million individuals think about suicide, 3.2 million make a plan to kill themselves, and more than 46,000 succeed, the investigators note.
The findings were published online in the Journal of Clinical Psychiatry.
Molecule mixture
Primarily used as an anesthetic in hospitals, ketamine is also taken illegally as a recreational drug. Users may aim for an intense high or feeling of dissociation, or an out-of-body–type experience.
Ketamine is a mixture of two mirror-image molecules. An intranasal version of one of these molecules (esketamine) is approved by the U.S. Food and Drug Administration for TRD. Both esketamine and ketamine are believed to increase neurotrophic signaling that affects synaptic function.
The study included 424 patients (mean age, 41.7 years) with major depressive disorder or another mood disorder and who received at least one ketamine infusion at a specialty clinic. Most participants had failed prior medication trials.
Patients in the study were typically started on 0.5 mg/kg of ketamine, with the dose titrated to achieve symptoms of partial dissociation. The median dose administered after titration was 0.93 mg/kg over 40 minutes.
The main treatment course of at least six infusions within 21 days was completed by 70% of the patients.
At each clinic visit, all participants completed the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 (GAD-7).
The primary outcome was PHQ-9 total scores, for which researchers looked at seven time periods: 1 week, 2-3 weeks, 4-6 weeks, 7-12 weeks, 13-24 weeks, 25-51 weeks, and 52+ weeks.
‘Blows it out of the water’
Results showed PHQ-9 total scores declined by 50% throughout the course of treatment, with much of the improvement gained within 4-6 weeks. There was a significant difference between week 1 and all later time periods (all P values < .001) and between weeks 2 and 3 and all later periods (all P values < .001).
Other measures included treatment response, defined as at least a 50% improvement on the PHQ-9, and depression remission, defined as a PHQ-9 score of less than 5. After three infusions, 14% of the patients responded and 7% were in remission. After 10 infusions, 72% responded and 38% were in remission.
These results compare favorably to other depression treatments, said Dr. Oliver. “Truthfully, with the exception of ECT [electroconvulsive therapy], this blows it all out of the water,” he added.
Dr. Oliver noted that the success rate for repetitive transcranial magnetic stimulation is 40%-60% depending on the modality; and for selective serotonin reuptake inhibitors, the success rate “is somewhere between the mid-20s and low-30s percent range.”
Another outcome measure was the self-harm/suicidal ideation item of the PHQ-9 questionnaire, which asks about “thoughts that you would be better off dead, or of hurting yourself in some way.” About 22% of the study participants no longer reported suicidal ideation after 3 infusions, 50% by 6 infusions, and 75% by 10 infusions.
By 15 infusions, 85% no longer reported these thoughts. “Nothing else has shown that, ever,” said Dr. Oliver.
Symptoms of generalized anxiety were also substantially improved. There was about a 30% reduction in the GAD-7 score during treatment and, again, most of the response occurred by 4-6 weeks.
Study limitations
Sex, age, and other demographic characteristics did not predict response or remission, but suicide planning trended toward higher response rates (P = .083). This suggests that a more depressed subgroup can achieve greater benefit from the treatment than can less symptomatic patients, the investigators note.
A history of psychosis also trended toward better response to treatment (P = .086) but not remission.
The researchers note that study limitations include that it was retrospective, lacked a control group, and did not require patients to be hospitalized – so the study sample may have been less severely ill than in other studies.
In addition, most patients paid out of pocket for the treatment at $495 per infusion, and they self-reported their symptoms.
As well, the researchers did not assess adverse events, although nurses made follow-up calls to patients. Dr. Oliver noted the most common side effects of ketamine are nausea, vomiting, and anxiety.
Previous research has suggested that ketamine therapy is not linked to long-term side effects, such as sexual dysfunction, weight gain, lethargy, or cognitive issues, said Dr. Oliver.
The investigators point out another study limitation was lack of detailed demographic information, such as race, income, and education, which might affect its generalizability.
Concerns and questions
Pouya Movahed Rad, MD, PhD, senior consultant and researcher in psychiatry, Lund (Sweden) University, noted several concerns, including that the clinics treating the study participants with ketamine profited from it.
He also speculated about who can afford the treatment because only a few patients in the study were reimbursed through insurance.
Dr. Movahed Rad was not involved with the current research but was principal investigator for a recent study that compared intravenous ketamine to ECT.
He questioned whether the patient population in the new study really was “real world.” Well-designed randomized controlled trials have been carried out in a “naturalistic setting, [which] get closer to real-life patients,” he said.
He also noted that the median dose after clinician titration (0.93 mg/kg over 40 minutes) “may be considered very high.”
With regard to doses being titrated to achieve symptoms of partial dissociation, “there is no obvious evidence to my knowledge that patients need to develop dissociative symptoms in order to have antidepressant effect,” said Dr. Movahed Rad.
Finally, he noted that the finding that 28% of the participants were using illegal drugs “is worrying” and wondered what drugs they were taking; he also questioned why 81% of the study population needed to take antidepressants.
The study did not receive outside funding. Dr. Oliver is the founder of MindPeace Clinics, which specialize in ketamine therapeutics. Dr. Movahed Rad has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests.
Results from a retrospective chart review analysis, which included more than 400 participants with TRD, illustrate that ketamine is a safe and rapid treatment in a real-world patient population, lead author Patrick A. Oliver, MD, founder and medical director, MindPeace Clinics, Richmond, Va., told this news organization.
The effect was perhaps most notable for reducing suicidal ideation, he said.
“In 2 weeks, we can take somebody from being suicidal to nonsuicidal. It’s a total game changer,” Dr. Oliver added.
Every year in the United States, about 12 million individuals think about suicide, 3.2 million make a plan to kill themselves, and more than 46,000 succeed, the investigators note.
The findings were published online in the Journal of Clinical Psychiatry.
Molecule mixture
Primarily used as an anesthetic in hospitals, ketamine is also taken illegally as a recreational drug. Users may aim for an intense high or feeling of dissociation, or an out-of-body–type experience.
Ketamine is a mixture of two mirror-image molecules. An intranasal version of one of these molecules (esketamine) is approved by the U.S. Food and Drug Administration for TRD. Both esketamine and ketamine are believed to increase neurotrophic signaling that affects synaptic function.
The study included 424 patients (mean age, 41.7 years) with major depressive disorder or another mood disorder and who received at least one ketamine infusion at a specialty clinic. Most participants had failed prior medication trials.
Patients in the study were typically started on 0.5 mg/kg of ketamine, with the dose titrated to achieve symptoms of partial dissociation. The median dose administered after titration was 0.93 mg/kg over 40 minutes.
The main treatment course of at least six infusions within 21 days was completed by 70% of the patients.
At each clinic visit, all participants completed the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 (GAD-7).
The primary outcome was PHQ-9 total scores, for which researchers looked at seven time periods: 1 week, 2-3 weeks, 4-6 weeks, 7-12 weeks, 13-24 weeks, 25-51 weeks, and 52+ weeks.
‘Blows it out of the water’
Results showed PHQ-9 total scores declined by 50% throughout the course of treatment, with much of the improvement gained within 4-6 weeks. There was a significant difference between week 1 and all later time periods (all P values < .001) and between weeks 2 and 3 and all later periods (all P values < .001).
Other measures included treatment response, defined as at least a 50% improvement on the PHQ-9, and depression remission, defined as a PHQ-9 score of less than 5. After three infusions, 14% of the patients responded and 7% were in remission. After 10 infusions, 72% responded and 38% were in remission.
These results compare favorably to other depression treatments, said Dr. Oliver. “Truthfully, with the exception of ECT [electroconvulsive therapy], this blows it all out of the water,” he added.
Dr. Oliver noted that the success rate for repetitive transcranial magnetic stimulation is 40%-60% depending on the modality; and for selective serotonin reuptake inhibitors, the success rate “is somewhere between the mid-20s and low-30s percent range.”
Another outcome measure was the self-harm/suicidal ideation item of the PHQ-9 questionnaire, which asks about “thoughts that you would be better off dead, or of hurting yourself in some way.” About 22% of the study participants no longer reported suicidal ideation after 3 infusions, 50% by 6 infusions, and 75% by 10 infusions.
By 15 infusions, 85% no longer reported these thoughts. “Nothing else has shown that, ever,” said Dr. Oliver.
Symptoms of generalized anxiety were also substantially improved. There was about a 30% reduction in the GAD-7 score during treatment and, again, most of the response occurred by 4-6 weeks.
Study limitations
Sex, age, and other demographic characteristics did not predict response or remission, but suicide planning trended toward higher response rates (P = .083). This suggests that a more depressed subgroup can achieve greater benefit from the treatment than can less symptomatic patients, the investigators note.
A history of psychosis also trended toward better response to treatment (P = .086) but not remission.
The researchers note that study limitations include that it was retrospective, lacked a control group, and did not require patients to be hospitalized – so the study sample may have been less severely ill than in other studies.
In addition, most patients paid out of pocket for the treatment at $495 per infusion, and they self-reported their symptoms.
As well, the researchers did not assess adverse events, although nurses made follow-up calls to patients. Dr. Oliver noted the most common side effects of ketamine are nausea, vomiting, and anxiety.
Previous research has suggested that ketamine therapy is not linked to long-term side effects, such as sexual dysfunction, weight gain, lethargy, or cognitive issues, said Dr. Oliver.
The investigators point out another study limitation was lack of detailed demographic information, such as race, income, and education, which might affect its generalizability.
Concerns and questions
Pouya Movahed Rad, MD, PhD, senior consultant and researcher in psychiatry, Lund (Sweden) University, noted several concerns, including that the clinics treating the study participants with ketamine profited from it.
He also speculated about who can afford the treatment because only a few patients in the study were reimbursed through insurance.
Dr. Movahed Rad was not involved with the current research but was principal investigator for a recent study that compared intravenous ketamine to ECT.
He questioned whether the patient population in the new study really was “real world.” Well-designed randomized controlled trials have been carried out in a “naturalistic setting, [which] get closer to real-life patients,” he said.
He also noted that the median dose after clinician titration (0.93 mg/kg over 40 minutes) “may be considered very high.”
With regard to doses being titrated to achieve symptoms of partial dissociation, “there is no obvious evidence to my knowledge that patients need to develop dissociative symptoms in order to have antidepressant effect,” said Dr. Movahed Rad.
Finally, he noted that the finding that 28% of the participants were using illegal drugs “is worrying” and wondered what drugs they were taking; he also questioned why 81% of the study population needed to take antidepressants.
The study did not receive outside funding. Dr. Oliver is the founder of MindPeace Clinics, which specialize in ketamine therapeutics. Dr. Movahed Rad has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests.
Results from a retrospective chart review analysis, which included more than 400 participants with TRD, illustrate that ketamine is a safe and rapid treatment in a real-world patient population, lead author Patrick A. Oliver, MD, founder and medical director, MindPeace Clinics, Richmond, Va., told this news organization.
The effect was perhaps most notable for reducing suicidal ideation, he said.
“In 2 weeks, we can take somebody from being suicidal to nonsuicidal. It’s a total game changer,” Dr. Oliver added.
Every year in the United States, about 12 million individuals think about suicide, 3.2 million make a plan to kill themselves, and more than 46,000 succeed, the investigators note.
The findings were published online in the Journal of Clinical Psychiatry.
Molecule mixture
Primarily used as an anesthetic in hospitals, ketamine is also taken illegally as a recreational drug. Users may aim for an intense high or feeling of dissociation, or an out-of-body–type experience.
Ketamine is a mixture of two mirror-image molecules. An intranasal version of one of these molecules (esketamine) is approved by the U.S. Food and Drug Administration for TRD. Both esketamine and ketamine are believed to increase neurotrophic signaling that affects synaptic function.
The study included 424 patients (mean age, 41.7 years) with major depressive disorder or another mood disorder and who received at least one ketamine infusion at a specialty clinic. Most participants had failed prior medication trials.
Patients in the study were typically started on 0.5 mg/kg of ketamine, with the dose titrated to achieve symptoms of partial dissociation. The median dose administered after titration was 0.93 mg/kg over 40 minutes.
The main treatment course of at least six infusions within 21 days was completed by 70% of the patients.
At each clinic visit, all participants completed the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 (GAD-7).
The primary outcome was PHQ-9 total scores, for which researchers looked at seven time periods: 1 week, 2-3 weeks, 4-6 weeks, 7-12 weeks, 13-24 weeks, 25-51 weeks, and 52+ weeks.
‘Blows it out of the water’
Results showed PHQ-9 total scores declined by 50% throughout the course of treatment, with much of the improvement gained within 4-6 weeks. There was a significant difference between week 1 and all later time periods (all P values < .001) and between weeks 2 and 3 and all later periods (all P values < .001).
Other measures included treatment response, defined as at least a 50% improvement on the PHQ-9, and depression remission, defined as a PHQ-9 score of less than 5. After three infusions, 14% of the patients responded and 7% were in remission. After 10 infusions, 72% responded and 38% were in remission.
These results compare favorably to other depression treatments, said Dr. Oliver. “Truthfully, with the exception of ECT [electroconvulsive therapy], this blows it all out of the water,” he added.
Dr. Oliver noted that the success rate for repetitive transcranial magnetic stimulation is 40%-60% depending on the modality; and for selective serotonin reuptake inhibitors, the success rate “is somewhere between the mid-20s and low-30s percent range.”
Another outcome measure was the self-harm/suicidal ideation item of the PHQ-9 questionnaire, which asks about “thoughts that you would be better off dead, or of hurting yourself in some way.” About 22% of the study participants no longer reported suicidal ideation after 3 infusions, 50% by 6 infusions, and 75% by 10 infusions.
By 15 infusions, 85% no longer reported these thoughts. “Nothing else has shown that, ever,” said Dr. Oliver.
Symptoms of generalized anxiety were also substantially improved. There was about a 30% reduction in the GAD-7 score during treatment and, again, most of the response occurred by 4-6 weeks.
Study limitations
Sex, age, and other demographic characteristics did not predict response or remission, but suicide planning trended toward higher response rates (P = .083). This suggests that a more depressed subgroup can achieve greater benefit from the treatment than can less symptomatic patients, the investigators note.
A history of psychosis also trended toward better response to treatment (P = .086) but not remission.
The researchers note that study limitations include that it was retrospective, lacked a control group, and did not require patients to be hospitalized – so the study sample may have been less severely ill than in other studies.
In addition, most patients paid out of pocket for the treatment at $495 per infusion, and they self-reported their symptoms.
As well, the researchers did not assess adverse events, although nurses made follow-up calls to patients. Dr. Oliver noted the most common side effects of ketamine are nausea, vomiting, and anxiety.
Previous research has suggested that ketamine therapy is not linked to long-term side effects, such as sexual dysfunction, weight gain, lethargy, or cognitive issues, said Dr. Oliver.
The investigators point out another study limitation was lack of detailed demographic information, such as race, income, and education, which might affect its generalizability.
Concerns and questions
Pouya Movahed Rad, MD, PhD, senior consultant and researcher in psychiatry, Lund (Sweden) University, noted several concerns, including that the clinics treating the study participants with ketamine profited from it.
He also speculated about who can afford the treatment because only a few patients in the study were reimbursed through insurance.
Dr. Movahed Rad was not involved with the current research but was principal investigator for a recent study that compared intravenous ketamine to ECT.
He questioned whether the patient population in the new study really was “real world.” Well-designed randomized controlled trials have been carried out in a “naturalistic setting, [which] get closer to real-life patients,” he said.
He also noted that the median dose after clinician titration (0.93 mg/kg over 40 minutes) “may be considered very high.”
With regard to doses being titrated to achieve symptoms of partial dissociation, “there is no obvious evidence to my knowledge that patients need to develop dissociative symptoms in order to have antidepressant effect,” said Dr. Movahed Rad.
Finally, he noted that the finding that 28% of the participants were using illegal drugs “is worrying” and wondered what drugs they were taking; he also questioned why 81% of the study population needed to take antidepressants.
The study did not receive outside funding. Dr. Oliver is the founder of MindPeace Clinics, which specialize in ketamine therapeutics. Dr. Movahed Rad has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JOURNAL OF CLINICAL PSYCHIATRY
COVID-19 linked to increased Alzheimer’s risk
The study of more than 6 million people aged 65 years or older found a 50%-80% increased risk for AD in the year after COVID-19; the risk was especially high for women older than 85 years.
However, the investigators were quick to point out that the observational retrospective study offers no evidence that COVID-19 causes AD. There could be a viral etiology at play, or the connection could be related to inflammation in neural tissue from the SARS-CoV-2 infection. Or it could simply be that exposure to the health care system for COVID-19 increased the odds of detection of existing undiagnosed AD cases.
Whatever the case, these findings point to a potential spike in AD cases, which is a cause for concern, study investigator Pamela Davis, MD, PhD, a professor in the Center for Community Health Integration at Case Western Reserve University, Cleveland, said in an interview.
“COVID may be giving us a legacy of ongoing medical difficulties,” Dr. Davis said. “We were already concerned about having a very large care burden and cost burden from Alzheimer’s disease. If this is another burden that’s increased by COVID, this is something we’re really going to have to prepare for.”
The findings were published online in Journal of Alzheimer’s Disease.
Increased risk
Earlier research points to a potential link between COVID-19 and increased risk for AD and Parkinson’s disease.
For the current study, researchers analyzed anonymous electronic health records of 6.2 million adults aged 65 years or older who received medical treatment between February 2020 and May 2021 and had no prior diagnosis of AD. The database includes information on almost 30% of the entire U.S. population.
Overall, there were 410,748 cases of COVID-19 during the study period.
The overall risk for new diagnosis of AD in the COVID-19 cohort was close to double that of those who did not have COVID-19 (0.68% vs. 0.35%, respectively).
After propensity-score matching, those who have had COVID-19 had a significantly higher risk for an AD diagnosis compared with those who were not infected (hazard ratio [HR], 1.69; 95% confidence interval [CI],1.53-1.72).
Risk for AD was elevated in all age groups, regardless of gender or ethnicity. Researchers did not collect data on COVID-19 severity, and the medical codes for long COVID were not published until after the study had ended.
Those with the highest risk were individuals older than 85 years (HR, 1.89; 95% CI, 1.73-2.07) and women (HR, 1.82; 95% CI, 1.69-1.97).
“We expected to see some impact, but I was surprised that it was as potent as it was,” Dr. Davis said.
Association, not causation
Heather Snyder, PhD, Alzheimer’s Association vice president of medical and scientific relations, who commented on the findings for this article, called the study interesting but emphasized caution in interpreting the results.
“Because this study only showed an association through medical records, we cannot know what the underlying mechanisms driving this association are without more research,” Dr. Snyder said. “If you have had COVID-19, it doesn’t mean you’re going to get dementia. But if you have had COVID-19 and are experiencing long-term symptoms including cognitive difficulties, talk to your doctor.”
Dr. Davis agreed, noting that this type of study offers information on association, but not causation. “I do think that this makes it imperative that we continue to follow the population for what’s going on in various neurodegenerative diseases,” Dr. Davis said.
The study was funded by the National Institute of Aging, National Institute on Alcohol Abuse and Alcoholism, the Clinical and Translational Science Collaborative of Cleveland, and the National Cancer Institute. Dr. Synder reports no relevant financial conflicts.
A version of this article first appeared on Medscape.com.
The study of more than 6 million people aged 65 years or older found a 50%-80% increased risk for AD in the year after COVID-19; the risk was especially high for women older than 85 years.
However, the investigators were quick to point out that the observational retrospective study offers no evidence that COVID-19 causes AD. There could be a viral etiology at play, or the connection could be related to inflammation in neural tissue from the SARS-CoV-2 infection. Or it could simply be that exposure to the health care system for COVID-19 increased the odds of detection of existing undiagnosed AD cases.
Whatever the case, these findings point to a potential spike in AD cases, which is a cause for concern, study investigator Pamela Davis, MD, PhD, a professor in the Center for Community Health Integration at Case Western Reserve University, Cleveland, said in an interview.
“COVID may be giving us a legacy of ongoing medical difficulties,” Dr. Davis said. “We were already concerned about having a very large care burden and cost burden from Alzheimer’s disease. If this is another burden that’s increased by COVID, this is something we’re really going to have to prepare for.”
The findings were published online in Journal of Alzheimer’s Disease.
Increased risk
Earlier research points to a potential link between COVID-19 and increased risk for AD and Parkinson’s disease.
For the current study, researchers analyzed anonymous electronic health records of 6.2 million adults aged 65 years or older who received medical treatment between February 2020 and May 2021 and had no prior diagnosis of AD. The database includes information on almost 30% of the entire U.S. population.
Overall, there were 410,748 cases of COVID-19 during the study period.
The overall risk for new diagnosis of AD in the COVID-19 cohort was close to double that of those who did not have COVID-19 (0.68% vs. 0.35%, respectively).
After propensity-score matching, those who have had COVID-19 had a significantly higher risk for an AD diagnosis compared with those who were not infected (hazard ratio [HR], 1.69; 95% confidence interval [CI],1.53-1.72).
Risk for AD was elevated in all age groups, regardless of gender or ethnicity. Researchers did not collect data on COVID-19 severity, and the medical codes for long COVID were not published until after the study had ended.
Those with the highest risk were individuals older than 85 years (HR, 1.89; 95% CI, 1.73-2.07) and women (HR, 1.82; 95% CI, 1.69-1.97).
“We expected to see some impact, but I was surprised that it was as potent as it was,” Dr. Davis said.
Association, not causation
Heather Snyder, PhD, Alzheimer’s Association vice president of medical and scientific relations, who commented on the findings for this article, called the study interesting but emphasized caution in interpreting the results.
“Because this study only showed an association through medical records, we cannot know what the underlying mechanisms driving this association are without more research,” Dr. Snyder said. “If you have had COVID-19, it doesn’t mean you’re going to get dementia. But if you have had COVID-19 and are experiencing long-term symptoms including cognitive difficulties, talk to your doctor.”
Dr. Davis agreed, noting that this type of study offers information on association, but not causation. “I do think that this makes it imperative that we continue to follow the population for what’s going on in various neurodegenerative diseases,” Dr. Davis said.
The study was funded by the National Institute of Aging, National Institute on Alcohol Abuse and Alcoholism, the Clinical and Translational Science Collaborative of Cleveland, and the National Cancer Institute. Dr. Synder reports no relevant financial conflicts.
A version of this article first appeared on Medscape.com.
The study of more than 6 million people aged 65 years or older found a 50%-80% increased risk for AD in the year after COVID-19; the risk was especially high for women older than 85 years.
However, the investigators were quick to point out that the observational retrospective study offers no evidence that COVID-19 causes AD. There could be a viral etiology at play, or the connection could be related to inflammation in neural tissue from the SARS-CoV-2 infection. Or it could simply be that exposure to the health care system for COVID-19 increased the odds of detection of existing undiagnosed AD cases.
Whatever the case, these findings point to a potential spike in AD cases, which is a cause for concern, study investigator Pamela Davis, MD, PhD, a professor in the Center for Community Health Integration at Case Western Reserve University, Cleveland, said in an interview.
“COVID may be giving us a legacy of ongoing medical difficulties,” Dr. Davis said. “We were already concerned about having a very large care burden and cost burden from Alzheimer’s disease. If this is another burden that’s increased by COVID, this is something we’re really going to have to prepare for.”
The findings were published online in Journal of Alzheimer’s Disease.
Increased risk
Earlier research points to a potential link between COVID-19 and increased risk for AD and Parkinson’s disease.
For the current study, researchers analyzed anonymous electronic health records of 6.2 million adults aged 65 years or older who received medical treatment between February 2020 and May 2021 and had no prior diagnosis of AD. The database includes information on almost 30% of the entire U.S. population.
Overall, there were 410,748 cases of COVID-19 during the study period.
The overall risk for new diagnosis of AD in the COVID-19 cohort was close to double that of those who did not have COVID-19 (0.68% vs. 0.35%, respectively).
After propensity-score matching, those who have had COVID-19 had a significantly higher risk for an AD diagnosis compared with those who were not infected (hazard ratio [HR], 1.69; 95% confidence interval [CI],1.53-1.72).
Risk for AD was elevated in all age groups, regardless of gender or ethnicity. Researchers did not collect data on COVID-19 severity, and the medical codes for long COVID were not published until after the study had ended.
Those with the highest risk were individuals older than 85 years (HR, 1.89; 95% CI, 1.73-2.07) and women (HR, 1.82; 95% CI, 1.69-1.97).
“We expected to see some impact, but I was surprised that it was as potent as it was,” Dr. Davis said.
Association, not causation
Heather Snyder, PhD, Alzheimer’s Association vice president of medical and scientific relations, who commented on the findings for this article, called the study interesting but emphasized caution in interpreting the results.
“Because this study only showed an association through medical records, we cannot know what the underlying mechanisms driving this association are without more research,” Dr. Snyder said. “If you have had COVID-19, it doesn’t mean you’re going to get dementia. But if you have had COVID-19 and are experiencing long-term symptoms including cognitive difficulties, talk to your doctor.”
Dr. Davis agreed, noting that this type of study offers information on association, but not causation. “I do think that this makes it imperative that we continue to follow the population for what’s going on in various neurodegenerative diseases,” Dr. Davis said.
The study was funded by the National Institute of Aging, National Institute on Alcohol Abuse and Alcoholism, the Clinical and Translational Science Collaborative of Cleveland, and the National Cancer Institute. Dr. Synder reports no relevant financial conflicts.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF ALZHEIMER’S DISEASE
Anesthesiologist arrested, implicated in death of colleague
at Baylor Scott & White Surgicare, a North Dallas surgical center. Raynaldo Rivera Ortiz Jr., MD, 59, is accused of injecting nerve-blocking and bronchodilating drugs into patient IV bags, resulting in at least one death and multiple cardiac emergencies.
In June, an anesthesiologist identified by Dallas ABC affiliate WFAA as Melanie Kaspar, MD, a colleague of Dr. Ortiz’s at the outpatient center, was ill and treated herself for dehydration using an IV bag of saline she had taken home from work. She died immediately after injecting the contents of the bag. According to the autopsy report, she died from a lethal dose of bupivacaine, a nerve-blocking agent often used during the administration of anesthesia. According to WFAA, Dr. Kaspar’s death was initially ruled accidental, but the Dallas County Medical Examiner has since reopened the case.
Then in August, an 18-year-old male patient, identified in court documents as J.A., experienced a cardiac emergency during a scheduled surgery at the clinic. The teen, who according to local press coverage was undergoing nose surgery after a dirt bike accident, was transferred to a local ICU. A chemical analysis of the fluid from the saline bag that was used during his surgery found epinephrine (a stimulant that could have caused his symptoms), bupivacaine, and lidocaine.
According to court documents, an investigation by the surgical center identified about 10 additional unexpected cardiac emergencies that occurred during what should have been unremarkable surgeries, an exceptionally high rate of complications, suggesting a pattern of intentional adulteration of IV bags. These surgeries were performed between May and August.
In addition, the complaint alleges that none of the cardiac incidents occurred during Dr. Ortiz’s surgeries; however, all of the incidents occurred around the time Dr. Ortiz performed services at the facility, and no incidents occurred while he was on vacation. The incidents began 2 days after Dr. Ortiz had been notified that he was the subject of a disciplinary inquiry stemming from an incident in which he allegedly “deviated from the standard of care” during an anesthesia procedure when a patient experienced a medical emergency, according to federal officials.
The complaint also alleges that Dr. Ortiz had a history of disciplinary actions against him, including at the facility, and he complained that the center was trying to “crucify” him.
Surveillance video from the hallway of the center’s operating room shows Dr. Ortiz placing IV bags in the stainless-steel bag warmer shortly before other doctors’ patients experienced cardiac emergencies, according to the complaint. In the description of one instance captured on video, Dr. Ortiz was observed walking quickly from an operating room to the bag warmer, placing a single IV bag inside, visually scanning the empty hallway, and quickly walking away. Just over an hour later, according to the complaint, a 56-year-old woman suffered a cardiac emergency during a scheduled cosmetic surgery after a bag from the warmer was used during her procedure.
The complaint alleges that in another instance, Dr. Ortiz was observed exiting his operating room carrying an IV bag concealed in what appeared to be a paper folder, swapping the bag with another bag from the warmer, and walking away. Roughly 30 minutes later, a 54-year-old woman suffered a cardiac emergency during a scheduled cosmetic surgery after a bag from the warmer was used during her procedure.
“Our complaint alleges this defendant surreptitiously injected heart-stopping drugs into patient IV bags, decimating the Hippocratic Oath,” said Chad E. Meacham, U.S. Attorney for the Northern District of Texas. “A single incident of seemingly intentional patient harm would be disconcerting; multiple incidents are truly disturbing. At this point, however, we believe that the problem is limited to one individual, who is currently behind bars. We will work tirelessly to hold him accountable.”
Dr. Ortiz is charged with tampering with a consumer product and with intentionally adulterating drugs. If convicted, he faces a maximum penalty of life in prison. Dr. Ortiz will make his initial appearance before U.S. Magistrate Judge Renee Toliver in Dallas Sept. 16.
On Sept. 9, the Texas Medical Board suspended Dr. Ortiz’s license in connection with this investigation, noting that the panel found “an imminent peril to the public health, safety, or welfare” and that Dr. Ortiz’s “continuation in the practice of medicine poses a continuing threat to public welfare.”
“It is astounding, stunning [for the victims] to think that anyone did this intentionally,” said Bruce W. Steckler, an attorney for some of the victims, in an interview with WFAA.
Baylor Scott & White Health, which operates the surgical center, said in a statement that the North Dallas facility will remain closed as the investigation continues.
“We actively assisted authorities in their investigation and will continue to do so. We also remain focused on communicating with patients,” the health system said.
A version of this article first appeared on Medscape.com.
at Baylor Scott & White Surgicare, a North Dallas surgical center. Raynaldo Rivera Ortiz Jr., MD, 59, is accused of injecting nerve-blocking and bronchodilating drugs into patient IV bags, resulting in at least one death and multiple cardiac emergencies.
In June, an anesthesiologist identified by Dallas ABC affiliate WFAA as Melanie Kaspar, MD, a colleague of Dr. Ortiz’s at the outpatient center, was ill and treated herself for dehydration using an IV bag of saline she had taken home from work. She died immediately after injecting the contents of the bag. According to the autopsy report, she died from a lethal dose of bupivacaine, a nerve-blocking agent often used during the administration of anesthesia. According to WFAA, Dr. Kaspar’s death was initially ruled accidental, but the Dallas County Medical Examiner has since reopened the case.
Then in August, an 18-year-old male patient, identified in court documents as J.A., experienced a cardiac emergency during a scheduled surgery at the clinic. The teen, who according to local press coverage was undergoing nose surgery after a dirt bike accident, was transferred to a local ICU. A chemical analysis of the fluid from the saline bag that was used during his surgery found epinephrine (a stimulant that could have caused his symptoms), bupivacaine, and lidocaine.
According to court documents, an investigation by the surgical center identified about 10 additional unexpected cardiac emergencies that occurred during what should have been unremarkable surgeries, an exceptionally high rate of complications, suggesting a pattern of intentional adulteration of IV bags. These surgeries were performed between May and August.
In addition, the complaint alleges that none of the cardiac incidents occurred during Dr. Ortiz’s surgeries; however, all of the incidents occurred around the time Dr. Ortiz performed services at the facility, and no incidents occurred while he was on vacation. The incidents began 2 days after Dr. Ortiz had been notified that he was the subject of a disciplinary inquiry stemming from an incident in which he allegedly “deviated from the standard of care” during an anesthesia procedure when a patient experienced a medical emergency, according to federal officials.
The complaint also alleges that Dr. Ortiz had a history of disciplinary actions against him, including at the facility, and he complained that the center was trying to “crucify” him.
Surveillance video from the hallway of the center’s operating room shows Dr. Ortiz placing IV bags in the stainless-steel bag warmer shortly before other doctors’ patients experienced cardiac emergencies, according to the complaint. In the description of one instance captured on video, Dr. Ortiz was observed walking quickly from an operating room to the bag warmer, placing a single IV bag inside, visually scanning the empty hallway, and quickly walking away. Just over an hour later, according to the complaint, a 56-year-old woman suffered a cardiac emergency during a scheduled cosmetic surgery after a bag from the warmer was used during her procedure.
The complaint alleges that in another instance, Dr. Ortiz was observed exiting his operating room carrying an IV bag concealed in what appeared to be a paper folder, swapping the bag with another bag from the warmer, and walking away. Roughly 30 minutes later, a 54-year-old woman suffered a cardiac emergency during a scheduled cosmetic surgery after a bag from the warmer was used during her procedure.
“Our complaint alleges this defendant surreptitiously injected heart-stopping drugs into patient IV bags, decimating the Hippocratic Oath,” said Chad E. Meacham, U.S. Attorney for the Northern District of Texas. “A single incident of seemingly intentional patient harm would be disconcerting; multiple incidents are truly disturbing. At this point, however, we believe that the problem is limited to one individual, who is currently behind bars. We will work tirelessly to hold him accountable.”
Dr. Ortiz is charged with tampering with a consumer product and with intentionally adulterating drugs. If convicted, he faces a maximum penalty of life in prison. Dr. Ortiz will make his initial appearance before U.S. Magistrate Judge Renee Toliver in Dallas Sept. 16.
On Sept. 9, the Texas Medical Board suspended Dr. Ortiz’s license in connection with this investigation, noting that the panel found “an imminent peril to the public health, safety, or welfare” and that Dr. Ortiz’s “continuation in the practice of medicine poses a continuing threat to public welfare.”
“It is astounding, stunning [for the victims] to think that anyone did this intentionally,” said Bruce W. Steckler, an attorney for some of the victims, in an interview with WFAA.
Baylor Scott & White Health, which operates the surgical center, said in a statement that the North Dallas facility will remain closed as the investigation continues.
“We actively assisted authorities in their investigation and will continue to do so. We also remain focused on communicating with patients,” the health system said.
A version of this article first appeared on Medscape.com.
at Baylor Scott & White Surgicare, a North Dallas surgical center. Raynaldo Rivera Ortiz Jr., MD, 59, is accused of injecting nerve-blocking and bronchodilating drugs into patient IV bags, resulting in at least one death and multiple cardiac emergencies.
In June, an anesthesiologist identified by Dallas ABC affiliate WFAA as Melanie Kaspar, MD, a colleague of Dr. Ortiz’s at the outpatient center, was ill and treated herself for dehydration using an IV bag of saline she had taken home from work. She died immediately after injecting the contents of the bag. According to the autopsy report, she died from a lethal dose of bupivacaine, a nerve-blocking agent often used during the administration of anesthesia. According to WFAA, Dr. Kaspar’s death was initially ruled accidental, but the Dallas County Medical Examiner has since reopened the case.
Then in August, an 18-year-old male patient, identified in court documents as J.A., experienced a cardiac emergency during a scheduled surgery at the clinic. The teen, who according to local press coverage was undergoing nose surgery after a dirt bike accident, was transferred to a local ICU. A chemical analysis of the fluid from the saline bag that was used during his surgery found epinephrine (a stimulant that could have caused his symptoms), bupivacaine, and lidocaine.
According to court documents, an investigation by the surgical center identified about 10 additional unexpected cardiac emergencies that occurred during what should have been unremarkable surgeries, an exceptionally high rate of complications, suggesting a pattern of intentional adulteration of IV bags. These surgeries were performed between May and August.
In addition, the complaint alleges that none of the cardiac incidents occurred during Dr. Ortiz’s surgeries; however, all of the incidents occurred around the time Dr. Ortiz performed services at the facility, and no incidents occurred while he was on vacation. The incidents began 2 days after Dr. Ortiz had been notified that he was the subject of a disciplinary inquiry stemming from an incident in which he allegedly “deviated from the standard of care” during an anesthesia procedure when a patient experienced a medical emergency, according to federal officials.
The complaint also alleges that Dr. Ortiz had a history of disciplinary actions against him, including at the facility, and he complained that the center was trying to “crucify” him.
Surveillance video from the hallway of the center’s operating room shows Dr. Ortiz placing IV bags in the stainless-steel bag warmer shortly before other doctors’ patients experienced cardiac emergencies, according to the complaint. In the description of one instance captured on video, Dr. Ortiz was observed walking quickly from an operating room to the bag warmer, placing a single IV bag inside, visually scanning the empty hallway, and quickly walking away. Just over an hour later, according to the complaint, a 56-year-old woman suffered a cardiac emergency during a scheduled cosmetic surgery after a bag from the warmer was used during her procedure.
The complaint alleges that in another instance, Dr. Ortiz was observed exiting his operating room carrying an IV bag concealed in what appeared to be a paper folder, swapping the bag with another bag from the warmer, and walking away. Roughly 30 minutes later, a 54-year-old woman suffered a cardiac emergency during a scheduled cosmetic surgery after a bag from the warmer was used during her procedure.
“Our complaint alleges this defendant surreptitiously injected heart-stopping drugs into patient IV bags, decimating the Hippocratic Oath,” said Chad E. Meacham, U.S. Attorney for the Northern District of Texas. “A single incident of seemingly intentional patient harm would be disconcerting; multiple incidents are truly disturbing. At this point, however, we believe that the problem is limited to one individual, who is currently behind bars. We will work tirelessly to hold him accountable.”
Dr. Ortiz is charged with tampering with a consumer product and with intentionally adulterating drugs. If convicted, he faces a maximum penalty of life in prison. Dr. Ortiz will make his initial appearance before U.S. Magistrate Judge Renee Toliver in Dallas Sept. 16.
On Sept. 9, the Texas Medical Board suspended Dr. Ortiz’s license in connection with this investigation, noting that the panel found “an imminent peril to the public health, safety, or welfare” and that Dr. Ortiz’s “continuation in the practice of medicine poses a continuing threat to public welfare.”
“It is astounding, stunning [for the victims] to think that anyone did this intentionally,” said Bruce W. Steckler, an attorney for some of the victims, in an interview with WFAA.
Baylor Scott & White Health, which operates the surgical center, said in a statement that the North Dallas facility will remain closed as the investigation continues.
“We actively assisted authorities in their investigation and will continue to do so. We also remain focused on communicating with patients,” the health system said.
A version of this article first appeared on Medscape.com.
Detachment predicts worse posttraumatic outcomes
The results highlight the importance of screening for dissociation in patients who have experienced trauma, study investigator Lauren A.M. Lebois, PhD, director of the dissociative disorders and trauma research program at McLean Hospital in Belmont, Mass., told this news organization.
“Clinicians could identify individuals potentially at risk of a chronic, more severe psychiatric course before these people go down that road, and they have the opportunity to connect folks with a phased trauma treatment approach to speed their recovery,” said Dr. Lebois, who is also an assistant professor of psychiatry at Harvard Medical School, Boston.
The study was published in the American Journal of Psychiatry.
Underdiagnosed
Feelings of detachment or derealization are a type of dissociation. Patients with the syndrome report feeling foggy or as if they are in a dream. Dissociative diagnoses are not rare and, in fact, are more prevalent than schizophrenia.
Research supports a powerful relationship between dissociation and traumatic experiences. However, dissociation is among the most stigmatized of psychiatric conditions. Even among clinicians and researchers, beliefs about dissociation are often not based on the scientific literature, said Dr. Lebois.
“For instance, skepticism, misunderstanding, and lack of professional education about dissociation all contribute to striking rates of underdiagnosis and misdiagnoses,” she said.
Dr. Lebois and colleagues used data from the larger Advancing Understanding of Recovery After Trauma (AURORA) study and included 1,464 adults, mean age 35 years, appearing at 22 U.S. emergency departments. Patients experienced a traumatic event such as a motor vehicle crash or physical or sexual assault.
About 2 weeks after the trauma, participants reported symptoms of derealization as measured by a two-item version of the Brief Dissociative Experiences Scale.
Brain imaging data
A subset of 145 patients underwent functional MRI (fMRI), during which they completed an emotion reactivity task (viewing fearful-looking human faces) and a resting-state scan.
In addition to measuring history of childhood maltreatment, researchers assessed posttraumatic stress symptom severity at 2 weeks and again at 3 months using the posttraumatic stress disorder checklist. Also at 3 months, they measured depression and anxiety symptoms, pain, and functional impairment.
About 55% of self-report participants and 50% of MRI participants endorsed some level of persistent derealization at 2 weeks.
After controlling for potential confounders, including sex, age, childhood maltreatment, and current posttraumatic stress symptoms, researchers found persistent derealization was associated with increased ventromedial prefrontal cortex (vmPFC) activity while viewing fearful faces.
The vmPFC helps to regulate emotional and physical reactions. “This region puts the ‘brakes’ on your emotional and physical reactivity – helping you to calm down” after a threatening or stressful experience has passed, said Dr. Lebois.
Researchers also found an association between higher self-reported derealization and decreased resting-state connectivity between the vmPFC and the orbitofrontal cortex and right lobule VIIIa – a region of the cerebellum involved in sensorimotor function.
“This may contribute to perceptual and affective distortions experienced during derealization – for example, feelings that surroundings are fading away, unreal, or strange,” said Dr. Lebois.
More pain, depression, anxiety
Higher levels of self-reported derealization at 2 weeks post trauma predicted higher levels of PTSD, anxiety, and depression as well as more bodily pain and impairment in work, family, and social life at 3 months.
“When we accounted for baseline levels of posttraumatic stress symptoms and trauma history, higher levels of self-reported derealization still predicted higher posttraumatic stress disorder and depression symptoms at 3 months,” said Dr. Lebois.
Additional adjusted analyses showed increased vmPFC activity during the fearful face task predicted 3-month self-reported PTSD symptoms.
Dr. Lebois “highly recommends” clinicians screen for dissociative symptoms, including derealization, in patients with trauma. Self-report screening tools are freely available online.
She noted patients with significant dissociative symptoms often do better with a “phase-oriented” approach to trauma treatment.
“In phase one, they learn emotional regulation skills to help them take more control over when they dissociate. Then they can successfully move on to trauma processing in phase two, which can involve exposure to trauma details.”
Although the field is not yet ready to use brain scans to diagnose dissociative symptoms, the new results “take us one step closer to being able to use objective neuroimaging biomarkers of derealization to augment subjective self-report measures,” said Dr. Lebois.
A limitation of the study was it could not determine a causal relationship, as some derealization may have been present before the traumatic event. The findings may not generalize to other types of dissociation, and the derealization assessment was measured only through a self-report 2 weeks after the trauma.
Another limitation was exclusion of patients with self-inflicted injuries or who were involved in domestic violence. The researchers noted the prevalence of derealization might have been even higher if such individuals were included.
An important investigation
In an accompanying editorial, Lisa M. Shin, PhD, department of psychology, Tufts University, and department of psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, notes having both clinical and neuroimaging variables as well as a large sample size makes the study “an important investigation” into predictors of psychiatric symptoms post-trauma.
Investigating a specific subtype of dissociation – persistent derealization – adds to the “novelty” of the study, she said.
The new findings “are certainly exciting for their potential clinical relevance and contributions to neurocircuitry models of PTSD,” she writes.
Some may argue administering a short, self-report measure of derealization “is far more efficient, cost-effective, and inclusive than conducting a specialized and expensive fMRI scan that is unlikely to be available to everyone,” notes Dr. Shin.
However, she added, a potential benefit of such a scan is identification of specific brain regions as potential targets for intervention. “For example, the results of this and other studies suggest that the vmPFC is a reasonable target for transcranial magnetic stimulation or its variants.”
The new results need to be replicated in a large, independent sample, said Dr. Shin. She added it would be helpful to know if other types of dissociation, and activation in other subregions of the vmPFC, also predict psychiatric outcomes after a trauma.
The study was supported by National Institute of Mental Health grants, the U.S. Army Medical Research and Material Command, One Mind, and the Mayday Fund. Dr. Lebois has received grant support from NIMH, and her spouse receives payments from Vanderbilt University for technology licensed to Acadia Pharmaceuticals. Dr. Shin receives textbook-related royalties from Pearson.
A version of this article first appeared on Medscape.com.
The results highlight the importance of screening for dissociation in patients who have experienced trauma, study investigator Lauren A.M. Lebois, PhD, director of the dissociative disorders and trauma research program at McLean Hospital in Belmont, Mass., told this news organization.
“Clinicians could identify individuals potentially at risk of a chronic, more severe psychiatric course before these people go down that road, and they have the opportunity to connect folks with a phased trauma treatment approach to speed their recovery,” said Dr. Lebois, who is also an assistant professor of psychiatry at Harvard Medical School, Boston.
The study was published in the American Journal of Psychiatry.
Underdiagnosed
Feelings of detachment or derealization are a type of dissociation. Patients with the syndrome report feeling foggy or as if they are in a dream. Dissociative diagnoses are not rare and, in fact, are more prevalent than schizophrenia.
Research supports a powerful relationship between dissociation and traumatic experiences. However, dissociation is among the most stigmatized of psychiatric conditions. Even among clinicians and researchers, beliefs about dissociation are often not based on the scientific literature, said Dr. Lebois.
“For instance, skepticism, misunderstanding, and lack of professional education about dissociation all contribute to striking rates of underdiagnosis and misdiagnoses,” she said.
Dr. Lebois and colleagues used data from the larger Advancing Understanding of Recovery After Trauma (AURORA) study and included 1,464 adults, mean age 35 years, appearing at 22 U.S. emergency departments. Patients experienced a traumatic event such as a motor vehicle crash or physical or sexual assault.
About 2 weeks after the trauma, participants reported symptoms of derealization as measured by a two-item version of the Brief Dissociative Experiences Scale.
Brain imaging data
A subset of 145 patients underwent functional MRI (fMRI), during which they completed an emotion reactivity task (viewing fearful-looking human faces) and a resting-state scan.
In addition to measuring history of childhood maltreatment, researchers assessed posttraumatic stress symptom severity at 2 weeks and again at 3 months using the posttraumatic stress disorder checklist. Also at 3 months, they measured depression and anxiety symptoms, pain, and functional impairment.
About 55% of self-report participants and 50% of MRI participants endorsed some level of persistent derealization at 2 weeks.
After controlling for potential confounders, including sex, age, childhood maltreatment, and current posttraumatic stress symptoms, researchers found persistent derealization was associated with increased ventromedial prefrontal cortex (vmPFC) activity while viewing fearful faces.
The vmPFC helps to regulate emotional and physical reactions. “This region puts the ‘brakes’ on your emotional and physical reactivity – helping you to calm down” after a threatening or stressful experience has passed, said Dr. Lebois.
Researchers also found an association between higher self-reported derealization and decreased resting-state connectivity between the vmPFC and the orbitofrontal cortex and right lobule VIIIa – a region of the cerebellum involved in sensorimotor function.
“This may contribute to perceptual and affective distortions experienced during derealization – for example, feelings that surroundings are fading away, unreal, or strange,” said Dr. Lebois.
More pain, depression, anxiety
Higher levels of self-reported derealization at 2 weeks post trauma predicted higher levels of PTSD, anxiety, and depression as well as more bodily pain and impairment in work, family, and social life at 3 months.
“When we accounted for baseline levels of posttraumatic stress symptoms and trauma history, higher levels of self-reported derealization still predicted higher posttraumatic stress disorder and depression symptoms at 3 months,” said Dr. Lebois.
Additional adjusted analyses showed increased vmPFC activity during the fearful face task predicted 3-month self-reported PTSD symptoms.
Dr. Lebois “highly recommends” clinicians screen for dissociative symptoms, including derealization, in patients with trauma. Self-report screening tools are freely available online.
She noted patients with significant dissociative symptoms often do better with a “phase-oriented” approach to trauma treatment.
“In phase one, they learn emotional regulation skills to help them take more control over when they dissociate. Then they can successfully move on to trauma processing in phase two, which can involve exposure to trauma details.”
Although the field is not yet ready to use brain scans to diagnose dissociative symptoms, the new results “take us one step closer to being able to use objective neuroimaging biomarkers of derealization to augment subjective self-report measures,” said Dr. Lebois.
A limitation of the study was it could not determine a causal relationship, as some derealization may have been present before the traumatic event. The findings may not generalize to other types of dissociation, and the derealization assessment was measured only through a self-report 2 weeks after the trauma.
Another limitation was exclusion of patients with self-inflicted injuries or who were involved in domestic violence. The researchers noted the prevalence of derealization might have been even higher if such individuals were included.
An important investigation
In an accompanying editorial, Lisa M. Shin, PhD, department of psychology, Tufts University, and department of psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, notes having both clinical and neuroimaging variables as well as a large sample size makes the study “an important investigation” into predictors of psychiatric symptoms post-trauma.
Investigating a specific subtype of dissociation – persistent derealization – adds to the “novelty” of the study, she said.
The new findings “are certainly exciting for their potential clinical relevance and contributions to neurocircuitry models of PTSD,” she writes.
Some may argue administering a short, self-report measure of derealization “is far more efficient, cost-effective, and inclusive than conducting a specialized and expensive fMRI scan that is unlikely to be available to everyone,” notes Dr. Shin.
However, she added, a potential benefit of such a scan is identification of specific brain regions as potential targets for intervention. “For example, the results of this and other studies suggest that the vmPFC is a reasonable target for transcranial magnetic stimulation or its variants.”
The new results need to be replicated in a large, independent sample, said Dr. Shin. She added it would be helpful to know if other types of dissociation, and activation in other subregions of the vmPFC, also predict psychiatric outcomes after a trauma.
The study was supported by National Institute of Mental Health grants, the U.S. Army Medical Research and Material Command, One Mind, and the Mayday Fund. Dr. Lebois has received grant support from NIMH, and her spouse receives payments from Vanderbilt University for technology licensed to Acadia Pharmaceuticals. Dr. Shin receives textbook-related royalties from Pearson.
A version of this article first appeared on Medscape.com.
The results highlight the importance of screening for dissociation in patients who have experienced trauma, study investigator Lauren A.M. Lebois, PhD, director of the dissociative disorders and trauma research program at McLean Hospital in Belmont, Mass., told this news organization.
“Clinicians could identify individuals potentially at risk of a chronic, more severe psychiatric course before these people go down that road, and they have the opportunity to connect folks with a phased trauma treatment approach to speed their recovery,” said Dr. Lebois, who is also an assistant professor of psychiatry at Harvard Medical School, Boston.
The study was published in the American Journal of Psychiatry.
Underdiagnosed
Feelings of detachment or derealization are a type of dissociation. Patients with the syndrome report feeling foggy or as if they are in a dream. Dissociative diagnoses are not rare and, in fact, are more prevalent than schizophrenia.
Research supports a powerful relationship between dissociation and traumatic experiences. However, dissociation is among the most stigmatized of psychiatric conditions. Even among clinicians and researchers, beliefs about dissociation are often not based on the scientific literature, said Dr. Lebois.
“For instance, skepticism, misunderstanding, and lack of professional education about dissociation all contribute to striking rates of underdiagnosis and misdiagnoses,” she said.
Dr. Lebois and colleagues used data from the larger Advancing Understanding of Recovery After Trauma (AURORA) study and included 1,464 adults, mean age 35 years, appearing at 22 U.S. emergency departments. Patients experienced a traumatic event such as a motor vehicle crash or physical or sexual assault.
About 2 weeks after the trauma, participants reported symptoms of derealization as measured by a two-item version of the Brief Dissociative Experiences Scale.
Brain imaging data
A subset of 145 patients underwent functional MRI (fMRI), during which they completed an emotion reactivity task (viewing fearful-looking human faces) and a resting-state scan.
In addition to measuring history of childhood maltreatment, researchers assessed posttraumatic stress symptom severity at 2 weeks and again at 3 months using the posttraumatic stress disorder checklist. Also at 3 months, they measured depression and anxiety symptoms, pain, and functional impairment.
About 55% of self-report participants and 50% of MRI participants endorsed some level of persistent derealization at 2 weeks.
After controlling for potential confounders, including sex, age, childhood maltreatment, and current posttraumatic stress symptoms, researchers found persistent derealization was associated with increased ventromedial prefrontal cortex (vmPFC) activity while viewing fearful faces.
The vmPFC helps to regulate emotional and physical reactions. “This region puts the ‘brakes’ on your emotional and physical reactivity – helping you to calm down” after a threatening or stressful experience has passed, said Dr. Lebois.
Researchers also found an association between higher self-reported derealization and decreased resting-state connectivity between the vmPFC and the orbitofrontal cortex and right lobule VIIIa – a region of the cerebellum involved in sensorimotor function.
“This may contribute to perceptual and affective distortions experienced during derealization – for example, feelings that surroundings are fading away, unreal, or strange,” said Dr. Lebois.
More pain, depression, anxiety
Higher levels of self-reported derealization at 2 weeks post trauma predicted higher levels of PTSD, anxiety, and depression as well as more bodily pain and impairment in work, family, and social life at 3 months.
“When we accounted for baseline levels of posttraumatic stress symptoms and trauma history, higher levels of self-reported derealization still predicted higher posttraumatic stress disorder and depression symptoms at 3 months,” said Dr. Lebois.
Additional adjusted analyses showed increased vmPFC activity during the fearful face task predicted 3-month self-reported PTSD symptoms.
Dr. Lebois “highly recommends” clinicians screen for dissociative symptoms, including derealization, in patients with trauma. Self-report screening tools are freely available online.
She noted patients with significant dissociative symptoms often do better with a “phase-oriented” approach to trauma treatment.
“In phase one, they learn emotional regulation skills to help them take more control over when they dissociate. Then they can successfully move on to trauma processing in phase two, which can involve exposure to trauma details.”
Although the field is not yet ready to use brain scans to diagnose dissociative symptoms, the new results “take us one step closer to being able to use objective neuroimaging biomarkers of derealization to augment subjective self-report measures,” said Dr. Lebois.
A limitation of the study was it could not determine a causal relationship, as some derealization may have been present before the traumatic event. The findings may not generalize to other types of dissociation, and the derealization assessment was measured only through a self-report 2 weeks after the trauma.
Another limitation was exclusion of patients with self-inflicted injuries or who were involved in domestic violence. The researchers noted the prevalence of derealization might have been even higher if such individuals were included.
An important investigation
In an accompanying editorial, Lisa M. Shin, PhD, department of psychology, Tufts University, and department of psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, notes having both clinical and neuroimaging variables as well as a large sample size makes the study “an important investigation” into predictors of psychiatric symptoms post-trauma.
Investigating a specific subtype of dissociation – persistent derealization – adds to the “novelty” of the study, she said.
The new findings “are certainly exciting for their potential clinical relevance and contributions to neurocircuitry models of PTSD,” she writes.
Some may argue administering a short, self-report measure of derealization “is far more efficient, cost-effective, and inclusive than conducting a specialized and expensive fMRI scan that is unlikely to be available to everyone,” notes Dr. Shin.
However, she added, a potential benefit of such a scan is identification of specific brain regions as potential targets for intervention. “For example, the results of this and other studies suggest that the vmPFC is a reasonable target for transcranial magnetic stimulation or its variants.”
The new results need to be replicated in a large, independent sample, said Dr. Shin. She added it would be helpful to know if other types of dissociation, and activation in other subregions of the vmPFC, also predict psychiatric outcomes after a trauma.
The study was supported by National Institute of Mental Health grants, the U.S. Army Medical Research and Material Command, One Mind, and the Mayday Fund. Dr. Lebois has received grant support from NIMH, and her spouse receives payments from Vanderbilt University for technology licensed to Acadia Pharmaceuticals. Dr. Shin receives textbook-related royalties from Pearson.
A version of this article first appeared on Medscape.com.
FROM AMERICAN JOURNAL OF PSYCHIATRY
Medical coding creates barriers to care for transgender patients
In 2021, Tim Chevalier received the first of many coverage denials from his insurance company for the hair-removal procedure he needed as part of a phalloplasty, the creation of a penis.
Electrolysis is a common procedure among transgender people like Mr. Chevalier, a software developer in Oakland, Calif.. In some cases, it’s used to remove unwanted hair from the face or body. But it’s also required for a phalloplasty or a vaginoplasty, the creation of a vagina, because all hair must be removed from the tissue that will be relocated during surgery.
Mr. Chevalier’s insurer, Anthem Blue Cross, told him he needed what’s known as a prior authorization for the procedure. Even after Mr. Chevalier received the authorization, he said, his reimbursement claims kept getting denied. According to Mr. Chevalier, Anthem said the procedure was considered cosmetic.
Many trans patients have trouble getting their insurers to cover gender-affirming care. One reason is transphobia within the U.S. health care system, but another involves how medical diagnoses and procedures are coded for insurance companies. Nationwide, health care providers use a list of diagnostic codes provided by the ICD-10. And many of those, advocates for transgender people say, haven’t caught up to the needs of patients. Such diagnostic codes provide the basis for determining which procedures, such as electrolysis or surgery, insurance will cover.
“It’s widely regarded that the codes are very limited in ICD-10,” said Johanna Olson-Kennedy, MD, medical director of the Center for Transyouth Health and Development at Children’s Hospital Los Angeles.
She advocates for a move to the 11th edition of the coding system, which was endorsed by the World Health Organization in 2019 and began to be adopted around the globe in February. Today, more than 34 countries use ICD-11.
The new edition has replaced outdated terms like “transsexualism” and “gender identity disorder” with “gender incongruence,” which is no longer classified as a mental health condition, but as a sexual health one. This is crucial in reducing the stigmatization of trans people in health care, said Dr. Olson-Kennedy.
A move away from the mental health classification may also mean more coverage of gender-affirming care by insurance companies, which sometimes question mental health claims more rigorously than those for physical illnesses. WHO officials have said they hope that adding gender incongruence to a sexual health chapter will “help increase access to care for health interventions” and “destigmatize the condition,” according to the WHO website.
However, history suggests that ICD-11 likely won’t be implemented in the United States for years. The WHO first endorsed ICD-10 in 1990, but the United States didn’t implement it for 25 years.
Meanwhile, patients who identify as transgender and their doctors are spending hours trying to get coverage – or using crowdfunding to cover big out-of-pocket bills. Mr. Chevalier estimated he has received 78 hours of electrolysis at $140 per hour, costing $10,920.
Anthem spokesperson Michael Bowman wrote in an email that “there has been no medical denials or denial of coverage” because Anthem “preapproved coverage for these services.”
However, even after the preapproval was given, Anthem responded to Mr. Chevalier’s claims by stating the electrolysis would not be reimbursed because the procedure is considered cosmetic, rather than medically necessary. This is regardless of Mr. Chevalier’s diagnosis of gender dysphoria – the psychological distress felt when someone’s biological sex and gender identity don’t match – which many doctors consider a medically legitimate reason for hair removal.
Bowman wrote that “once this issue was identified, Anthem implemented an internal process which included a manual override in the billing system.”
Still, Mr. Chevalier filed a complaint with the California Department of Managed Health Care, and the state declared Anthem Blue Cross out of compliance. Additionally, after KHN started asking Anthem questions about Chevalier’s bills, two claims that had not been addressed since April were resolved in July. So far, Anthem has reimbursed Chevalier around $8,000.
Some procedures that trans patients receive can also be excluded from coverage because insurance companies consider them “sex specific.” For example, a transgender man’s gynecological visit may not be covered because his insurance plan covers those visits only for people enrolled as women.
“There is always this question of: What gender should you tell the insurance company?” said Nick Gorton, MD, an emergency medicine physician in Davis, Calif. Dr. Gorton, who is trans, recommends his patients with insurance plans that exclude trans care calculate the out-of-pocket costs that would be required for certain procedures based on whether the patient lists themselves as male or female on their insurance paperwork. For example, Dr. Gorton said, the question for a trans man becomes “what’s more expensive – paying for testosterone or paying for a Pap smear?” – since insurance likely won’t cover both.
For years, some physicians helped trans patients get coverage by finding other medical reasons for their trans-related care. Dr. Gorton said that if, for instance, a transgender man wanted a hysterectomy but his insurance didn’t cover gender-affirming care, Dr. Gorton would enter the ICD-10 code for pelvic pain, as opposed to gender dysphoria, into the patient’s billing record. Pelvic pain is a legitimate reason for the surgery and is commonly accepted by insurance providers, Dr. Gorton said. But some insurance companies pushed back, and he had to find other ways to help his patients.
In 2005, California passed a first-of-its-kind law that prohibits discrimination by health insurance on the basis of gender or gender identity. Now, 24 states and Washington, D.C., forbid private insurance from excluding transgender-related health care benefits.
Consequently, Dr. Gorton no longer needs to use different codes for patients seeking gender-affirming care at his practice in California. But physicians in other states are still struggling.
When Eric Meininger, MD, MPH, an internist and pediatrician at Indiana University Health’s gender health program in Indianapolis, treats a trans kid seeking hormone therapy, he commonly uses the ICD-10 code for “medication management” as the primary reason for the patient’s visit. That’s because Indiana has no law providing insurance protections for LGBTQ+ people, and when gender dysphoria is listed as the primary reason, insurance companies have denied coverage.
“It’s frustrating,” Dr. Meininger said. In a patient’s billing record, he sometimes provides multiple diagnoses, including gender dysphoria, to increase the likelihood that a procedure will be covered. “It’s not hard usually to come up with five or seven or eight diagnoses for someone because there’s lots of vague ones out there.”
Implementing ICD-11 won’t fix all the coding problems, as insurance companies may still refuse to cover procedures related to gender incongruence even though it is listed as a sexual health condition. It also won’t change the fact that many states still allow insurance to exclude gender-affirming care. But in terms of reducing stigma, it’s a step forward, Dr. Olson-Kennedy said.
One reason the United States took so long to switch to ICD-10 is that the American Medical Association strongly opposed the move. It argued the new system would put an incredible burden on doctors. Physicians would have to “contend with 68,000 diagnosis codes – a fivefold increase from the approximately 13,000 diagnosis codes in use today,” the AMA wrote in a 2014 letter. Implementing software to update providers’ coding systems would also be costly, dealing a financial blow to small medical practices, the association argued.
Unlike past coding systems, ICD-11 is fully electronic, with no physical manual of codes, and can be incorporated into a medical facility’s current coding system without requiring a new rollout, said Christian Lindmeier, a WHO spokesperson.
Whether these changes will make the adoption of the new edition easier in the United States is yet to be seen. For now, many trans patients in need of gender-affirming care must pay their bills out of pocket, fight their insurance company for coverage, or rely on the generosity of others.
“Even though I did get reimbursed eventually, the reimbursements were delayed, and it burned up a lot of my time,” Mr. Chevalier said. “Most people would have just given up.”
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
In 2021, Tim Chevalier received the first of many coverage denials from his insurance company for the hair-removal procedure he needed as part of a phalloplasty, the creation of a penis.
Electrolysis is a common procedure among transgender people like Mr. Chevalier, a software developer in Oakland, Calif.. In some cases, it’s used to remove unwanted hair from the face or body. But it’s also required for a phalloplasty or a vaginoplasty, the creation of a vagina, because all hair must be removed from the tissue that will be relocated during surgery.
Mr. Chevalier’s insurer, Anthem Blue Cross, told him he needed what’s known as a prior authorization for the procedure. Even after Mr. Chevalier received the authorization, he said, his reimbursement claims kept getting denied. According to Mr. Chevalier, Anthem said the procedure was considered cosmetic.
Many trans patients have trouble getting their insurers to cover gender-affirming care. One reason is transphobia within the U.S. health care system, but another involves how medical diagnoses and procedures are coded for insurance companies. Nationwide, health care providers use a list of diagnostic codes provided by the ICD-10. And many of those, advocates for transgender people say, haven’t caught up to the needs of patients. Such diagnostic codes provide the basis for determining which procedures, such as electrolysis or surgery, insurance will cover.
“It’s widely regarded that the codes are very limited in ICD-10,” said Johanna Olson-Kennedy, MD, medical director of the Center for Transyouth Health and Development at Children’s Hospital Los Angeles.
She advocates for a move to the 11th edition of the coding system, which was endorsed by the World Health Organization in 2019 and began to be adopted around the globe in February. Today, more than 34 countries use ICD-11.
The new edition has replaced outdated terms like “transsexualism” and “gender identity disorder” with “gender incongruence,” which is no longer classified as a mental health condition, but as a sexual health one. This is crucial in reducing the stigmatization of trans people in health care, said Dr. Olson-Kennedy.
A move away from the mental health classification may also mean more coverage of gender-affirming care by insurance companies, which sometimes question mental health claims more rigorously than those for physical illnesses. WHO officials have said they hope that adding gender incongruence to a sexual health chapter will “help increase access to care for health interventions” and “destigmatize the condition,” according to the WHO website.
However, history suggests that ICD-11 likely won’t be implemented in the United States for years. The WHO first endorsed ICD-10 in 1990, but the United States didn’t implement it for 25 years.
Meanwhile, patients who identify as transgender and their doctors are spending hours trying to get coverage – or using crowdfunding to cover big out-of-pocket bills. Mr. Chevalier estimated he has received 78 hours of electrolysis at $140 per hour, costing $10,920.
Anthem spokesperson Michael Bowman wrote in an email that “there has been no medical denials or denial of coverage” because Anthem “preapproved coverage for these services.”
However, even after the preapproval was given, Anthem responded to Mr. Chevalier’s claims by stating the electrolysis would not be reimbursed because the procedure is considered cosmetic, rather than medically necessary. This is regardless of Mr. Chevalier’s diagnosis of gender dysphoria – the psychological distress felt when someone’s biological sex and gender identity don’t match – which many doctors consider a medically legitimate reason for hair removal.
Bowman wrote that “once this issue was identified, Anthem implemented an internal process which included a manual override in the billing system.”
Still, Mr. Chevalier filed a complaint with the California Department of Managed Health Care, and the state declared Anthem Blue Cross out of compliance. Additionally, after KHN started asking Anthem questions about Chevalier’s bills, two claims that had not been addressed since April were resolved in July. So far, Anthem has reimbursed Chevalier around $8,000.
Some procedures that trans patients receive can also be excluded from coverage because insurance companies consider them “sex specific.” For example, a transgender man’s gynecological visit may not be covered because his insurance plan covers those visits only for people enrolled as women.
“There is always this question of: What gender should you tell the insurance company?” said Nick Gorton, MD, an emergency medicine physician in Davis, Calif. Dr. Gorton, who is trans, recommends his patients with insurance plans that exclude trans care calculate the out-of-pocket costs that would be required for certain procedures based on whether the patient lists themselves as male or female on their insurance paperwork. For example, Dr. Gorton said, the question for a trans man becomes “what’s more expensive – paying for testosterone or paying for a Pap smear?” – since insurance likely won’t cover both.
For years, some physicians helped trans patients get coverage by finding other medical reasons for their trans-related care. Dr. Gorton said that if, for instance, a transgender man wanted a hysterectomy but his insurance didn’t cover gender-affirming care, Dr. Gorton would enter the ICD-10 code for pelvic pain, as opposed to gender dysphoria, into the patient’s billing record. Pelvic pain is a legitimate reason for the surgery and is commonly accepted by insurance providers, Dr. Gorton said. But some insurance companies pushed back, and he had to find other ways to help his patients.
In 2005, California passed a first-of-its-kind law that prohibits discrimination by health insurance on the basis of gender or gender identity. Now, 24 states and Washington, D.C., forbid private insurance from excluding transgender-related health care benefits.
Consequently, Dr. Gorton no longer needs to use different codes for patients seeking gender-affirming care at his practice in California. But physicians in other states are still struggling.
When Eric Meininger, MD, MPH, an internist and pediatrician at Indiana University Health’s gender health program in Indianapolis, treats a trans kid seeking hormone therapy, he commonly uses the ICD-10 code for “medication management” as the primary reason for the patient’s visit. That’s because Indiana has no law providing insurance protections for LGBTQ+ people, and when gender dysphoria is listed as the primary reason, insurance companies have denied coverage.
“It’s frustrating,” Dr. Meininger said. In a patient’s billing record, he sometimes provides multiple diagnoses, including gender dysphoria, to increase the likelihood that a procedure will be covered. “It’s not hard usually to come up with five or seven or eight diagnoses for someone because there’s lots of vague ones out there.”
Implementing ICD-11 won’t fix all the coding problems, as insurance companies may still refuse to cover procedures related to gender incongruence even though it is listed as a sexual health condition. It also won’t change the fact that many states still allow insurance to exclude gender-affirming care. But in terms of reducing stigma, it’s a step forward, Dr. Olson-Kennedy said.
One reason the United States took so long to switch to ICD-10 is that the American Medical Association strongly opposed the move. It argued the new system would put an incredible burden on doctors. Physicians would have to “contend with 68,000 diagnosis codes – a fivefold increase from the approximately 13,000 diagnosis codes in use today,” the AMA wrote in a 2014 letter. Implementing software to update providers’ coding systems would also be costly, dealing a financial blow to small medical practices, the association argued.
Unlike past coding systems, ICD-11 is fully electronic, with no physical manual of codes, and can be incorporated into a medical facility’s current coding system without requiring a new rollout, said Christian Lindmeier, a WHO spokesperson.
Whether these changes will make the adoption of the new edition easier in the United States is yet to be seen. For now, many trans patients in need of gender-affirming care must pay their bills out of pocket, fight their insurance company for coverage, or rely on the generosity of others.
“Even though I did get reimbursed eventually, the reimbursements were delayed, and it burned up a lot of my time,” Mr. Chevalier said. “Most people would have just given up.”
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
In 2021, Tim Chevalier received the first of many coverage denials from his insurance company for the hair-removal procedure he needed as part of a phalloplasty, the creation of a penis.
Electrolysis is a common procedure among transgender people like Mr. Chevalier, a software developer in Oakland, Calif.. In some cases, it’s used to remove unwanted hair from the face or body. But it’s also required for a phalloplasty or a vaginoplasty, the creation of a vagina, because all hair must be removed from the tissue that will be relocated during surgery.
Mr. Chevalier’s insurer, Anthem Blue Cross, told him he needed what’s known as a prior authorization for the procedure. Even after Mr. Chevalier received the authorization, he said, his reimbursement claims kept getting denied. According to Mr. Chevalier, Anthem said the procedure was considered cosmetic.
Many trans patients have trouble getting their insurers to cover gender-affirming care. One reason is transphobia within the U.S. health care system, but another involves how medical diagnoses and procedures are coded for insurance companies. Nationwide, health care providers use a list of diagnostic codes provided by the ICD-10. And many of those, advocates for transgender people say, haven’t caught up to the needs of patients. Such diagnostic codes provide the basis for determining which procedures, such as electrolysis or surgery, insurance will cover.
“It’s widely regarded that the codes are very limited in ICD-10,” said Johanna Olson-Kennedy, MD, medical director of the Center for Transyouth Health and Development at Children’s Hospital Los Angeles.
She advocates for a move to the 11th edition of the coding system, which was endorsed by the World Health Organization in 2019 and began to be adopted around the globe in February. Today, more than 34 countries use ICD-11.
The new edition has replaced outdated terms like “transsexualism” and “gender identity disorder” with “gender incongruence,” which is no longer classified as a mental health condition, but as a sexual health one. This is crucial in reducing the stigmatization of trans people in health care, said Dr. Olson-Kennedy.
A move away from the mental health classification may also mean more coverage of gender-affirming care by insurance companies, which sometimes question mental health claims more rigorously than those for physical illnesses. WHO officials have said they hope that adding gender incongruence to a sexual health chapter will “help increase access to care for health interventions” and “destigmatize the condition,” according to the WHO website.
However, history suggests that ICD-11 likely won’t be implemented in the United States for years. The WHO first endorsed ICD-10 in 1990, but the United States didn’t implement it for 25 years.
Meanwhile, patients who identify as transgender and their doctors are spending hours trying to get coverage – or using crowdfunding to cover big out-of-pocket bills. Mr. Chevalier estimated he has received 78 hours of electrolysis at $140 per hour, costing $10,920.
Anthem spokesperson Michael Bowman wrote in an email that “there has been no medical denials or denial of coverage” because Anthem “preapproved coverage for these services.”
However, even after the preapproval was given, Anthem responded to Mr. Chevalier’s claims by stating the electrolysis would not be reimbursed because the procedure is considered cosmetic, rather than medically necessary. This is regardless of Mr. Chevalier’s diagnosis of gender dysphoria – the psychological distress felt when someone’s biological sex and gender identity don’t match – which many doctors consider a medically legitimate reason for hair removal.
Bowman wrote that “once this issue was identified, Anthem implemented an internal process which included a manual override in the billing system.”
Still, Mr. Chevalier filed a complaint with the California Department of Managed Health Care, and the state declared Anthem Blue Cross out of compliance. Additionally, after KHN started asking Anthem questions about Chevalier’s bills, two claims that had not been addressed since April were resolved in July. So far, Anthem has reimbursed Chevalier around $8,000.
Some procedures that trans patients receive can also be excluded from coverage because insurance companies consider them “sex specific.” For example, a transgender man’s gynecological visit may not be covered because his insurance plan covers those visits only for people enrolled as women.
“There is always this question of: What gender should you tell the insurance company?” said Nick Gorton, MD, an emergency medicine physician in Davis, Calif. Dr. Gorton, who is trans, recommends his patients with insurance plans that exclude trans care calculate the out-of-pocket costs that would be required for certain procedures based on whether the patient lists themselves as male or female on their insurance paperwork. For example, Dr. Gorton said, the question for a trans man becomes “what’s more expensive – paying for testosterone or paying for a Pap smear?” – since insurance likely won’t cover both.
For years, some physicians helped trans patients get coverage by finding other medical reasons for their trans-related care. Dr. Gorton said that if, for instance, a transgender man wanted a hysterectomy but his insurance didn’t cover gender-affirming care, Dr. Gorton would enter the ICD-10 code for pelvic pain, as opposed to gender dysphoria, into the patient’s billing record. Pelvic pain is a legitimate reason for the surgery and is commonly accepted by insurance providers, Dr. Gorton said. But some insurance companies pushed back, and he had to find other ways to help his patients.
In 2005, California passed a first-of-its-kind law that prohibits discrimination by health insurance on the basis of gender or gender identity. Now, 24 states and Washington, D.C., forbid private insurance from excluding transgender-related health care benefits.
Consequently, Dr. Gorton no longer needs to use different codes for patients seeking gender-affirming care at his practice in California. But physicians in other states are still struggling.
When Eric Meininger, MD, MPH, an internist and pediatrician at Indiana University Health’s gender health program in Indianapolis, treats a trans kid seeking hormone therapy, he commonly uses the ICD-10 code for “medication management” as the primary reason for the patient’s visit. That’s because Indiana has no law providing insurance protections for LGBTQ+ people, and when gender dysphoria is listed as the primary reason, insurance companies have denied coverage.
“It’s frustrating,” Dr. Meininger said. In a patient’s billing record, he sometimes provides multiple diagnoses, including gender dysphoria, to increase the likelihood that a procedure will be covered. “It’s not hard usually to come up with five or seven or eight diagnoses for someone because there’s lots of vague ones out there.”
Implementing ICD-11 won’t fix all the coding problems, as insurance companies may still refuse to cover procedures related to gender incongruence even though it is listed as a sexual health condition. It also won’t change the fact that many states still allow insurance to exclude gender-affirming care. But in terms of reducing stigma, it’s a step forward, Dr. Olson-Kennedy said.
One reason the United States took so long to switch to ICD-10 is that the American Medical Association strongly opposed the move. It argued the new system would put an incredible burden on doctors. Physicians would have to “contend with 68,000 diagnosis codes – a fivefold increase from the approximately 13,000 diagnosis codes in use today,” the AMA wrote in a 2014 letter. Implementing software to update providers’ coding systems would also be costly, dealing a financial blow to small medical practices, the association argued.
Unlike past coding systems, ICD-11 is fully electronic, with no physical manual of codes, and can be incorporated into a medical facility’s current coding system without requiring a new rollout, said Christian Lindmeier, a WHO spokesperson.
Whether these changes will make the adoption of the new edition easier in the United States is yet to be seen. For now, many trans patients in need of gender-affirming care must pay their bills out of pocket, fight their insurance company for coverage, or rely on the generosity of others.
“Even though I did get reimbursed eventually, the reimbursements were delayed, and it burned up a lot of my time,” Mr. Chevalier said. “Most people would have just given up.”
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
Time to cancer diagnoses in U.S. averages 5 months
Time to diagnosis is a crucial factor in cancer. Delays can lead to diagnosis at later stages and prevent optimal therapeutic strategies, both of which have the potential to reduce survival. An estimated 63%-82% of cancers get diagnosed as a result of symptom presentation, and delays in diagnosis can hamper treatment efforts. Diagnosis can be challenging because common symptoms – such as weight loss, weakness, poor appetite, and shortness of breath – are nonspecific.
A new analysis of U.S.-based data shows that the average time to diagnosis is 5.2 months for patients with solid tumors. The authors of the study call for better cancer diagnosis pathways in the U.S.
“Several countries, including the UK, Denmark, Sweden, Canada and Australia, have identified the importance and potential impact of more timely diagnosis by establishing national guidelines, special programs, and treatment pathways. However, in the U.S., there’s relatively little research and effort focused on streamlining the diagnostic pathway. Currently, the U.S. does not have established cancer diagnostic pathways that are used consistently,” Matthew Gitlin, PharmD, said during a presentation at the annual meeting of the European Society for Medical Oncology.
“That is often associated with worse clinical outcomes, increased economic burden, and decreased health related quality of life,” said Dr. Gitlin, founder and managing director of the health economics consulting firm BluePath Solutions, which conducted the analysis.
The study retrospectively examined administrative billing data drawn from the Clinformatics for Managed Markets longitudinal database. The data represent individuals in Medicare Advantage and a large, U.S.-based private insurance plan. Between 2018 and 2019, there were 458,818 cancer diagnoses. The mean age was 70.6 years and 49.6% of the patients were female. Sixty-five percent were White, 11.1% Black, 8.3% Hispanic, and 2.5% Asian. No race data were available for 13.2%. Medicare Advantage was the primary insurance carrier for 74.0%, and 24.0% had a commercial plan.
The mean time to diagnosis across all tumors was 5.2 months (standard deviation, 5.5 months). There was significant variation across different tumor types, as well as within the same tumor type. The median value was 3.9 months (interquartile range, 1.1-7.2 months).
Mean time to diagnosis ranged from 121.6 days for bladder cancer to as high as 229 days for multiple myeloma. Standard deviations were nearly as large or even larger than the mean values. The study showed that 15.8% of patients waited 6 months or longer for a diagnosis. Delays were most common in kidney cancer, colorectal cancer, gallbladder cancer, esophageal cancer, stomach cancer, lymphoma, and multiple myeloma: More than 25% of patients had a time to diagnosis of at least 6 months in these tumors.
“Although there is limited research in the published literature, our findings are consistent with that literature that does exist. Development or modification of policies, guidelines or medical interventions that streamline the diagnostic pathway are needed to optimize patient outcomes and reduce resource burden and cost to the health care system,” Dr. Gitlin said.
Previous literature on this topic has seen wide variation in how time to diagnosis is defined, and most research is conducted in high-income countries, according to Felipe Roitberg, PhD, who served as a discussant during the session. “Most of the countries and patients in need are localized in low- and middle-income countries, so that is a call to action (for more research),” said Dr. Roitberg, a clinical oncologist at Hospital Sírio Libanês in São Paulo, Brazil.
The study did not look at the associations between race and time to diagnosis. “This is a source of analysis could further be explored,” said Dr. Roitberg.
He noted that the ABC-DO prospective cohort study in sub-Saharan Africa found large variations in breast cancer survival by country, and its authors predicted that downstaging and improvements in treatment could prevent up to one-third of projected breast cancer deaths over the next decade. “So these are the drivers of populational gain in terms of overall survival – not more drugs, not more services available, but coordination of services and making sure the patient has a right pathway (to diagnosis and treatment),” Dr. Roitberg said.
Dr. Gitlin has received consulting fees from GRAIL LLC, which is a subsidiary of Illumina. Dr. Roitberg has received honoraria from Boehringer Ingelheim, Sanofi, Roche, MSD Oncology, AstraZeneca, Nestle Health Science, Dr Reddy’s, and Oncologia Brazil. He has consulted for MSD Oncology. He has received research funding from Roche, Boehringer Ingelheim, MSD, Bayer, AstraZeneca, and Takeda.
Time to diagnosis is a crucial factor in cancer. Delays can lead to diagnosis at later stages and prevent optimal therapeutic strategies, both of which have the potential to reduce survival. An estimated 63%-82% of cancers get diagnosed as a result of symptom presentation, and delays in diagnosis can hamper treatment efforts. Diagnosis can be challenging because common symptoms – such as weight loss, weakness, poor appetite, and shortness of breath – are nonspecific.
A new analysis of U.S.-based data shows that the average time to diagnosis is 5.2 months for patients with solid tumors. The authors of the study call for better cancer diagnosis pathways in the U.S.
“Several countries, including the UK, Denmark, Sweden, Canada and Australia, have identified the importance and potential impact of more timely diagnosis by establishing national guidelines, special programs, and treatment pathways. However, in the U.S., there’s relatively little research and effort focused on streamlining the diagnostic pathway. Currently, the U.S. does not have established cancer diagnostic pathways that are used consistently,” Matthew Gitlin, PharmD, said during a presentation at the annual meeting of the European Society for Medical Oncology.
“That is often associated with worse clinical outcomes, increased economic burden, and decreased health related quality of life,” said Dr. Gitlin, founder and managing director of the health economics consulting firm BluePath Solutions, which conducted the analysis.
The study retrospectively examined administrative billing data drawn from the Clinformatics for Managed Markets longitudinal database. The data represent individuals in Medicare Advantage and a large, U.S.-based private insurance plan. Between 2018 and 2019, there were 458,818 cancer diagnoses. The mean age was 70.6 years and 49.6% of the patients were female. Sixty-five percent were White, 11.1% Black, 8.3% Hispanic, and 2.5% Asian. No race data were available for 13.2%. Medicare Advantage was the primary insurance carrier for 74.0%, and 24.0% had a commercial plan.
The mean time to diagnosis across all tumors was 5.2 months (standard deviation, 5.5 months). There was significant variation across different tumor types, as well as within the same tumor type. The median value was 3.9 months (interquartile range, 1.1-7.2 months).
Mean time to diagnosis ranged from 121.6 days for bladder cancer to as high as 229 days for multiple myeloma. Standard deviations were nearly as large or even larger than the mean values. The study showed that 15.8% of patients waited 6 months or longer for a diagnosis. Delays were most common in kidney cancer, colorectal cancer, gallbladder cancer, esophageal cancer, stomach cancer, lymphoma, and multiple myeloma: More than 25% of patients had a time to diagnosis of at least 6 months in these tumors.
“Although there is limited research in the published literature, our findings are consistent with that literature that does exist. Development or modification of policies, guidelines or medical interventions that streamline the diagnostic pathway are needed to optimize patient outcomes and reduce resource burden and cost to the health care system,” Dr. Gitlin said.
Previous literature on this topic has seen wide variation in how time to diagnosis is defined, and most research is conducted in high-income countries, according to Felipe Roitberg, PhD, who served as a discussant during the session. “Most of the countries and patients in need are localized in low- and middle-income countries, so that is a call to action (for more research),” said Dr. Roitberg, a clinical oncologist at Hospital Sírio Libanês in São Paulo, Brazil.
The study did not look at the associations between race and time to diagnosis. “This is a source of analysis could further be explored,” said Dr. Roitberg.
He noted that the ABC-DO prospective cohort study in sub-Saharan Africa found large variations in breast cancer survival by country, and its authors predicted that downstaging and improvements in treatment could prevent up to one-third of projected breast cancer deaths over the next decade. “So these are the drivers of populational gain in terms of overall survival – not more drugs, not more services available, but coordination of services and making sure the patient has a right pathway (to diagnosis and treatment),” Dr. Roitberg said.
Dr. Gitlin has received consulting fees from GRAIL LLC, which is a subsidiary of Illumina. Dr. Roitberg has received honoraria from Boehringer Ingelheim, Sanofi, Roche, MSD Oncology, AstraZeneca, Nestle Health Science, Dr Reddy’s, and Oncologia Brazil. He has consulted for MSD Oncology. He has received research funding from Roche, Boehringer Ingelheim, MSD, Bayer, AstraZeneca, and Takeda.
Time to diagnosis is a crucial factor in cancer. Delays can lead to diagnosis at later stages and prevent optimal therapeutic strategies, both of which have the potential to reduce survival. An estimated 63%-82% of cancers get diagnosed as a result of symptom presentation, and delays in diagnosis can hamper treatment efforts. Diagnosis can be challenging because common symptoms – such as weight loss, weakness, poor appetite, and shortness of breath – are nonspecific.
A new analysis of U.S.-based data shows that the average time to diagnosis is 5.2 months for patients with solid tumors. The authors of the study call for better cancer diagnosis pathways in the U.S.
“Several countries, including the UK, Denmark, Sweden, Canada and Australia, have identified the importance and potential impact of more timely diagnosis by establishing national guidelines, special programs, and treatment pathways. However, in the U.S., there’s relatively little research and effort focused on streamlining the diagnostic pathway. Currently, the U.S. does not have established cancer diagnostic pathways that are used consistently,” Matthew Gitlin, PharmD, said during a presentation at the annual meeting of the European Society for Medical Oncology.
“That is often associated with worse clinical outcomes, increased economic burden, and decreased health related quality of life,” said Dr. Gitlin, founder and managing director of the health economics consulting firm BluePath Solutions, which conducted the analysis.
The study retrospectively examined administrative billing data drawn from the Clinformatics for Managed Markets longitudinal database. The data represent individuals in Medicare Advantage and a large, U.S.-based private insurance plan. Between 2018 and 2019, there were 458,818 cancer diagnoses. The mean age was 70.6 years and 49.6% of the patients were female. Sixty-five percent were White, 11.1% Black, 8.3% Hispanic, and 2.5% Asian. No race data were available for 13.2%. Medicare Advantage was the primary insurance carrier for 74.0%, and 24.0% had a commercial plan.
The mean time to diagnosis across all tumors was 5.2 months (standard deviation, 5.5 months). There was significant variation across different tumor types, as well as within the same tumor type. The median value was 3.9 months (interquartile range, 1.1-7.2 months).
Mean time to diagnosis ranged from 121.6 days for bladder cancer to as high as 229 days for multiple myeloma. Standard deviations were nearly as large or even larger than the mean values. The study showed that 15.8% of patients waited 6 months or longer for a diagnosis. Delays were most common in kidney cancer, colorectal cancer, gallbladder cancer, esophageal cancer, stomach cancer, lymphoma, and multiple myeloma: More than 25% of patients had a time to diagnosis of at least 6 months in these tumors.
“Although there is limited research in the published literature, our findings are consistent with that literature that does exist. Development or modification of policies, guidelines or medical interventions that streamline the diagnostic pathway are needed to optimize patient outcomes and reduce resource burden and cost to the health care system,” Dr. Gitlin said.
Previous literature on this topic has seen wide variation in how time to diagnosis is defined, and most research is conducted in high-income countries, according to Felipe Roitberg, PhD, who served as a discussant during the session. “Most of the countries and patients in need are localized in low- and middle-income countries, so that is a call to action (for more research),” said Dr. Roitberg, a clinical oncologist at Hospital Sírio Libanês in São Paulo, Brazil.
The study did not look at the associations between race and time to diagnosis. “This is a source of analysis could further be explored,” said Dr. Roitberg.
He noted that the ABC-DO prospective cohort study in sub-Saharan Africa found large variations in breast cancer survival by country, and its authors predicted that downstaging and improvements in treatment could prevent up to one-third of projected breast cancer deaths over the next decade. “So these are the drivers of populational gain in terms of overall survival – not more drugs, not more services available, but coordination of services and making sure the patient has a right pathway (to diagnosis and treatment),” Dr. Roitberg said.
Dr. Gitlin has received consulting fees from GRAIL LLC, which is a subsidiary of Illumina. Dr. Roitberg has received honoraria from Boehringer Ingelheim, Sanofi, Roche, MSD Oncology, AstraZeneca, Nestle Health Science, Dr Reddy’s, and Oncologia Brazil. He has consulted for MSD Oncology. He has received research funding from Roche, Boehringer Ingelheim, MSD, Bayer, AstraZeneca, and Takeda.
FROM ESMO CONGRESS 2022
BRAF/MEK combo shows long-term efficacy in melanoma
, according to 5-year follow-up data from the COLUMBUS trial. Among patients with advanced unresectable or metastatic disease who were untreated or who had progressed following immunotherapy, the regimen of encorafenib plus binimetinib produced impressive gains in progression-free and overall survival, compared with historical controls, and are in line with other BRAF/MEK inhibitor combinations. It also outperformed encorafenib and vemurafenib monotherapy regimens.
The findings present good news, but the combination still doesn’t represent the best first-line option, according to Ryan Sullivan, MD, who wrote an accompanying editorial. He pointed out that the previously published DREAMSeq trial showed that a combination of immune checkpoint inhibitors (ICIs) ipilimumab and nivolumab produced a 2-year survival of 72%, compared with 52% for a BRAF inhibitor combination of dabrafenib plus trametinib (P = .0095).
There are three combinations of BRAF and MEK inhibitors that are approved for BRAF mutant melanoma, and any of the seven individual agents and six combinations that are approved by the U.S. Food and Drug Administration- for melanoma can be used in BRAFV600 patients. “The standard of care for most patients with newly diagnosed BRAF mutant melanoma is ... immune checkpoint inhibition, either with anti–PD-1 inhibitor or a combination of immunotherapy with an anti–PD-1 inhibitor. The optimal use of BRAF targeted therapy is unknown but some data supports its use earlier in the disease course (adjuvant setting) or after progression following anti–PD-1 therapy in the advanced disease setting,” wrote Dr. Sullivan in an email. He is associate director of the melanoma program at Massachusetts General Hospital, Boston.
The new study was published online in the Journal of Clinical Oncology.
In his editorial, Dr. Sullivan wrote that anti–PD-1 monoclonal antibodies alone or in combination with anti-CTLA4 receptor therapies is likely the best front-line therapy for BRAFV600 mutant advanced melanoma, with long-term survival ranging from 40% to 50%.
Still, the efficacy of BRAF-targeted therapy makes it important to explore ways to strengthen it further. One possibility is to use it in the front-line setting when a patient is at high risk of rapid progression and death, since analysis from DREAMSeq showed that BRAF-targeted therapy had a better overall survival than immunotherapy during the first 10 months after random assignment. It was only after this time point that the curves reversed and pointed to greater efficacy for immunotherapy. An option would be to treat to maximum tumor regression with BRAF-targeted therapy and then switch to immunotherapy, according to Dr. Sullivan. That point was echoed by study author Paolo Ascierto, MD, in an email exchange. “For patients with symptomatic disease or very high tumor burden, BRAF/MEK inhibitor should be used first,” said Dr. Ascierto, who is director of the melanoma cancer immunotherapy innovative therapy unit of the National Tumor Institute in Naples, Italy.
BRAF inhibitors as second- or later-line therapy
Aside from that exception, BRAF inhibitors should generally be reserved for second- or later-line therapy, according to Dr. Sullivan. Retrospective data indicate that response to BRAF inhibitors is preserved following immunotherapy, although the duration of benefit is reduced. Unfortunately, that strategy limits BRAF inhibitors to a setting in which they’re less likely to be maximally effective.
To improve matters, Dr. Sullivan suggested that they could be used in the adjuvant setting, where disease burden is lower. He noted that dabrafenib and trametinib are approved for resected stage 3 melanoma and showed similar efficacy to immunotherapy in that setting. Immunotherapy retains efficacy after BRAF-targeted therapy.
Another potential strategy is to come up with 3- or even 4-drug combinations employing BRAF/MEK inhibitors in the second-line setting. A few trials have already begun to investigate this possibility.
The COLUMBUS trial included 192 patients who received encorafenib plus binimetinib (E+B), 191 who received vemurafenib and 194 who received encorafenib. Five-year progression-free survival (PFS) was 23% in the E+B group, and 31% in those with normal lactate dehydrogenase levels. Five-year PFS was 10% with vemurafenib alone (12% with normal lactate dehydrogenase). Progression free survival (PFS) was 19% in the encorafenib group. Five-year overall survival (OS) followed a similar trend: 35% (45% with normal lactate dehydrogenase) in the E+B group, and 21% (28%) in the vemurafenib group. E+B had a median duration of response of 18.6 months, and a disease control rate of 92.2%, compared with 12.3 months and 81.2% with vemurafenib. Median duration of response was 15.5 months in the encorafenib monotherapy group.
The COLUMBUS trial was sponsored by Array BioPharma, which was acquired by Pfizer in July 2019.
Dr. Sullivan has consulted or advised Novartis, Merck, Replimune, Asana Biosciences, Alkermes, Eisai, Pfizer, Iovance Biotherapeutics, OncoSec, AstraZeneca, and Bristol Myers Squibb. Dr. Ascierto has stock or an ownership position in PrimeVax. He has consulted or advised for Bristol Myers Squibb, Roche/Genentech, Merck Sharp & Dohme, Novartis, Array BioPharma, Merck Serono, Pierre Fabre, Incyte, MedImmune, AstraZeneca, Sun Pharma, Sanofi, Idera, Ultimovacs, Sandoz, Immunocore, 4SC, Alkermes, Italfarmaco, Nektar, Boehringer Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Pfizer, OncoSec, Nouscom, Takis Biotech, Lunaphore Technologies, Seattle Genetics, ITeos Therapeutics, Medicenna, and Bio-Al Health.
, according to 5-year follow-up data from the COLUMBUS trial. Among patients with advanced unresectable or metastatic disease who were untreated or who had progressed following immunotherapy, the regimen of encorafenib plus binimetinib produced impressive gains in progression-free and overall survival, compared with historical controls, and are in line with other BRAF/MEK inhibitor combinations. It also outperformed encorafenib and vemurafenib monotherapy regimens.
The findings present good news, but the combination still doesn’t represent the best first-line option, according to Ryan Sullivan, MD, who wrote an accompanying editorial. He pointed out that the previously published DREAMSeq trial showed that a combination of immune checkpoint inhibitors (ICIs) ipilimumab and nivolumab produced a 2-year survival of 72%, compared with 52% for a BRAF inhibitor combination of dabrafenib plus trametinib (P = .0095).
There are three combinations of BRAF and MEK inhibitors that are approved for BRAF mutant melanoma, and any of the seven individual agents and six combinations that are approved by the U.S. Food and Drug Administration- for melanoma can be used in BRAFV600 patients. “The standard of care for most patients with newly diagnosed BRAF mutant melanoma is ... immune checkpoint inhibition, either with anti–PD-1 inhibitor or a combination of immunotherapy with an anti–PD-1 inhibitor. The optimal use of BRAF targeted therapy is unknown but some data supports its use earlier in the disease course (adjuvant setting) or after progression following anti–PD-1 therapy in the advanced disease setting,” wrote Dr. Sullivan in an email. He is associate director of the melanoma program at Massachusetts General Hospital, Boston.
The new study was published online in the Journal of Clinical Oncology.
In his editorial, Dr. Sullivan wrote that anti–PD-1 monoclonal antibodies alone or in combination with anti-CTLA4 receptor therapies is likely the best front-line therapy for BRAFV600 mutant advanced melanoma, with long-term survival ranging from 40% to 50%.
Still, the efficacy of BRAF-targeted therapy makes it important to explore ways to strengthen it further. One possibility is to use it in the front-line setting when a patient is at high risk of rapid progression and death, since analysis from DREAMSeq showed that BRAF-targeted therapy had a better overall survival than immunotherapy during the first 10 months after random assignment. It was only after this time point that the curves reversed and pointed to greater efficacy for immunotherapy. An option would be to treat to maximum tumor regression with BRAF-targeted therapy and then switch to immunotherapy, according to Dr. Sullivan. That point was echoed by study author Paolo Ascierto, MD, in an email exchange. “For patients with symptomatic disease or very high tumor burden, BRAF/MEK inhibitor should be used first,” said Dr. Ascierto, who is director of the melanoma cancer immunotherapy innovative therapy unit of the National Tumor Institute in Naples, Italy.
BRAF inhibitors as second- or later-line therapy
Aside from that exception, BRAF inhibitors should generally be reserved for second- or later-line therapy, according to Dr. Sullivan. Retrospective data indicate that response to BRAF inhibitors is preserved following immunotherapy, although the duration of benefit is reduced. Unfortunately, that strategy limits BRAF inhibitors to a setting in which they’re less likely to be maximally effective.
To improve matters, Dr. Sullivan suggested that they could be used in the adjuvant setting, where disease burden is lower. He noted that dabrafenib and trametinib are approved for resected stage 3 melanoma and showed similar efficacy to immunotherapy in that setting. Immunotherapy retains efficacy after BRAF-targeted therapy.
Another potential strategy is to come up with 3- or even 4-drug combinations employing BRAF/MEK inhibitors in the second-line setting. A few trials have already begun to investigate this possibility.
The COLUMBUS trial included 192 patients who received encorafenib plus binimetinib (E+B), 191 who received vemurafenib and 194 who received encorafenib. Five-year progression-free survival (PFS) was 23% in the E+B group, and 31% in those with normal lactate dehydrogenase levels. Five-year PFS was 10% with vemurafenib alone (12% with normal lactate dehydrogenase). Progression free survival (PFS) was 19% in the encorafenib group. Five-year overall survival (OS) followed a similar trend: 35% (45% with normal lactate dehydrogenase) in the E+B group, and 21% (28%) in the vemurafenib group. E+B had a median duration of response of 18.6 months, and a disease control rate of 92.2%, compared with 12.3 months and 81.2% with vemurafenib. Median duration of response was 15.5 months in the encorafenib monotherapy group.
The COLUMBUS trial was sponsored by Array BioPharma, which was acquired by Pfizer in July 2019.
Dr. Sullivan has consulted or advised Novartis, Merck, Replimune, Asana Biosciences, Alkermes, Eisai, Pfizer, Iovance Biotherapeutics, OncoSec, AstraZeneca, and Bristol Myers Squibb. Dr. Ascierto has stock or an ownership position in PrimeVax. He has consulted or advised for Bristol Myers Squibb, Roche/Genentech, Merck Sharp & Dohme, Novartis, Array BioPharma, Merck Serono, Pierre Fabre, Incyte, MedImmune, AstraZeneca, Sun Pharma, Sanofi, Idera, Ultimovacs, Sandoz, Immunocore, 4SC, Alkermes, Italfarmaco, Nektar, Boehringer Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Pfizer, OncoSec, Nouscom, Takis Biotech, Lunaphore Technologies, Seattle Genetics, ITeos Therapeutics, Medicenna, and Bio-Al Health.
, according to 5-year follow-up data from the COLUMBUS trial. Among patients with advanced unresectable or metastatic disease who were untreated or who had progressed following immunotherapy, the regimen of encorafenib plus binimetinib produced impressive gains in progression-free and overall survival, compared with historical controls, and are in line with other BRAF/MEK inhibitor combinations. It also outperformed encorafenib and vemurafenib monotherapy regimens.
The findings present good news, but the combination still doesn’t represent the best first-line option, according to Ryan Sullivan, MD, who wrote an accompanying editorial. He pointed out that the previously published DREAMSeq trial showed that a combination of immune checkpoint inhibitors (ICIs) ipilimumab and nivolumab produced a 2-year survival of 72%, compared with 52% for a BRAF inhibitor combination of dabrafenib plus trametinib (P = .0095).
There are three combinations of BRAF and MEK inhibitors that are approved for BRAF mutant melanoma, and any of the seven individual agents and six combinations that are approved by the U.S. Food and Drug Administration- for melanoma can be used in BRAFV600 patients. “The standard of care for most patients with newly diagnosed BRAF mutant melanoma is ... immune checkpoint inhibition, either with anti–PD-1 inhibitor or a combination of immunotherapy with an anti–PD-1 inhibitor. The optimal use of BRAF targeted therapy is unknown but some data supports its use earlier in the disease course (adjuvant setting) or after progression following anti–PD-1 therapy in the advanced disease setting,” wrote Dr. Sullivan in an email. He is associate director of the melanoma program at Massachusetts General Hospital, Boston.
The new study was published online in the Journal of Clinical Oncology.
In his editorial, Dr. Sullivan wrote that anti–PD-1 monoclonal antibodies alone or in combination with anti-CTLA4 receptor therapies is likely the best front-line therapy for BRAFV600 mutant advanced melanoma, with long-term survival ranging from 40% to 50%.
Still, the efficacy of BRAF-targeted therapy makes it important to explore ways to strengthen it further. One possibility is to use it in the front-line setting when a patient is at high risk of rapid progression and death, since analysis from DREAMSeq showed that BRAF-targeted therapy had a better overall survival than immunotherapy during the first 10 months after random assignment. It was only after this time point that the curves reversed and pointed to greater efficacy for immunotherapy. An option would be to treat to maximum tumor regression with BRAF-targeted therapy and then switch to immunotherapy, according to Dr. Sullivan. That point was echoed by study author Paolo Ascierto, MD, in an email exchange. “For patients with symptomatic disease or very high tumor burden, BRAF/MEK inhibitor should be used first,” said Dr. Ascierto, who is director of the melanoma cancer immunotherapy innovative therapy unit of the National Tumor Institute in Naples, Italy.
BRAF inhibitors as second- or later-line therapy
Aside from that exception, BRAF inhibitors should generally be reserved for second- or later-line therapy, according to Dr. Sullivan. Retrospective data indicate that response to BRAF inhibitors is preserved following immunotherapy, although the duration of benefit is reduced. Unfortunately, that strategy limits BRAF inhibitors to a setting in which they’re less likely to be maximally effective.
To improve matters, Dr. Sullivan suggested that they could be used in the adjuvant setting, where disease burden is lower. He noted that dabrafenib and trametinib are approved for resected stage 3 melanoma and showed similar efficacy to immunotherapy in that setting. Immunotherapy retains efficacy after BRAF-targeted therapy.
Another potential strategy is to come up with 3- or even 4-drug combinations employing BRAF/MEK inhibitors in the second-line setting. A few trials have already begun to investigate this possibility.
The COLUMBUS trial included 192 patients who received encorafenib plus binimetinib (E+B), 191 who received vemurafenib and 194 who received encorafenib. Five-year progression-free survival (PFS) was 23% in the E+B group, and 31% in those with normal lactate dehydrogenase levels. Five-year PFS was 10% with vemurafenib alone (12% with normal lactate dehydrogenase). Progression free survival (PFS) was 19% in the encorafenib group. Five-year overall survival (OS) followed a similar trend: 35% (45% with normal lactate dehydrogenase) in the E+B group, and 21% (28%) in the vemurafenib group. E+B had a median duration of response of 18.6 months, and a disease control rate of 92.2%, compared with 12.3 months and 81.2% with vemurafenib. Median duration of response was 15.5 months in the encorafenib monotherapy group.
The COLUMBUS trial was sponsored by Array BioPharma, which was acquired by Pfizer in July 2019.
Dr. Sullivan has consulted or advised Novartis, Merck, Replimune, Asana Biosciences, Alkermes, Eisai, Pfizer, Iovance Biotherapeutics, OncoSec, AstraZeneca, and Bristol Myers Squibb. Dr. Ascierto has stock or an ownership position in PrimeVax. He has consulted or advised for Bristol Myers Squibb, Roche/Genentech, Merck Sharp & Dohme, Novartis, Array BioPharma, Merck Serono, Pierre Fabre, Incyte, MedImmune, AstraZeneca, Sun Pharma, Sanofi, Idera, Ultimovacs, Sandoz, Immunocore, 4SC, Alkermes, Italfarmaco, Nektar, Boehringer Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Pfizer, OncoSec, Nouscom, Takis Biotech, Lunaphore Technologies, Seattle Genetics, ITeos Therapeutics, Medicenna, and Bio-Al Health.
FROM JOURNAL OF CLINICAL ONCOLOGY
New ESC guidelines for cutting CV risk in noncardiac surgery
The European Society of Cardiology guidelines on cardiovascular assessment and management of patients undergoing noncardiac surgery have seen extensive revision since the 2014 version.
They still have the same aim – to prevent surgery-related bleeding complications, perioperative myocardial infarction/injury (PMI), stent thrombosis, acute heart failure, arrhythmias, pulmonary embolism, ischemic stroke, and cardiovascular (CV) death.
Cochairpersons Sigrun Halvorsen, MD, PhD, and Julinda Mehilli, MD, presented highlights from the guidelines at the annual congress of the European Society of Cardiology and the document was simultaneously published online in the European Heart Journal.
The document classifies noncardiac surgery into three levels of 30-day risk of CV death, MI, or stroke. Low (< 1%) risk includes eye or thyroid surgery; intermediate (1%-5%) risk includes knee or hip replacement or renal transplant; and high (> 5%) risk includes aortic aneurysm, lung transplant, or pancreatic or bladder cancer surgery (see more examples below).
It classifies patients as low risk if they are younger than 65 without CV disease or CV risk factors (smoking, hypertension, diabetes, dyslipidemia, family history); intermediate risk if they are 65 or older or have CV risk factors; and high risk if they have CVD.
In an interview, Dr. Halvorsen, professor in cardiology, University of Oslo, zeroed in on three important revisions:
First, recommendations for preoperative ECG and biomarkers are more specific, he noted.
The guidelines advise that before intermediate- or high-risk noncardiac surgery, in patients who have known CVD, CV risk factors (including age 65 or older), or symptoms suggestive of CVD:
- It is recommended to obtain a preoperative 12-lead ECG (class I).
- It is recommended to measure high-sensitivity cardiac troponin T (hs-cTn T) or high-sensitivity cardiac troponin I (hs-cTn I). It is also recommended to measure these biomarkers at 24 hours and 48 hours post surgery (class I).
- It should be considered to measure B-type natriuretic peptide or N-terminal of the prohormone BNP (NT-proBNP).
However, for low-risk patients undergoing low- and intermediate-risk noncardiac surgery, it is not recommended to routinely obtain preoperative ECG, hs-cTn T/I, or BNP/NT-proBNP concentrations (class III).
Troponins have a stronger class I recommendation, compared with the IIA recommendation for BNP, because they are useful for preoperative risk stratification and for diagnosis of PMI, Dr. Halvorsen explained. “Patients receive painkillers after surgery and may have no pain,” she noted, but they may have PMI, which has a bad prognosis.
Second, the guidelines recommend that “all patients should stop smoking 4 weeks before noncardiac surgery [class I],” she noted. Clinicians should also “measure hemoglobin, and if the patient is anemic, treat the anemia.”
Third, the sections on antithrombotic treatment have been significantly revised. “Bridging – stopping an oral antithrombotic drug and switching to a subcutaneous or IV drug – has been common,” Dr. Halvorsen said, “but recently we have new evidence that in most cases that increases the risk of bleeding.”
“We are [now] much more restrictive with respect to bridging” with unfractionated heparin or low-molecular-weight heparin, she said. “We recommend against bridging in patients with low to moderate thrombotic risk,” and bridging should only be considered in patients with mechanical prosthetic heart valves or with very high thrombotic risk.
More preoperative recommendations
In the guideline overview session at the congress, Dr. Halverson highlighted some of the new recommendations for preoperative risk assessment.
If time allows, it is recommended to optimize guideline-recommended treatment of CVD and control of CV risk factors including blood pressure, dyslipidemia, and diabetes, before noncardiac surgery (class I).
Patients commonly have “murmurs, chest pain, dyspnea, and edema that may suggest severe CVD, but may also be caused by noncardiac disease,” she noted. The guidelines state that “for patients with a newly detected murmur and symptoms or signs of CVD, transthoracic echocardiography is recommended before noncardiac surgery (class I).
“Many studies have been performed to try to find out if initiation of specific drugs before surgery could reduce the risk of complications,” Dr. Halvorsen noted. However, few have shown any benefit and “the question of presurgery initiation of beta-blockers has been greatly debated,” she said. “We have again reviewed the literature and concluded ‘Routine initiation of beta-blockers perioperatively is not recommended (class IIIA).’ “
“We adhere to the guidelines on acute and chronic coronary syndrome recommending 6-12 months of dual antiplatelet treatment as a standard before elective surgery,” she said. “However, in case of time-sensitive surgery, the duration of that treatment can be shortened down to a minimum of 1 month after elective PCI and a minimum of 3 months after PCI and ACS.”
Patients with specific types of CVD
Dr. Mehilli, a professor at Landshut-Achdorf (Germany) Hospital, highlighted some new guideline recommendations for patients who have specific types of cardiovascular disease.
Coronary artery disease (CAD). “For chronic coronary syndrome, a cardiac workup is recommended only for patients undergoing intermediate risk or high-risk noncardiac surgery.”
“Stress imaging should be considered before any high risk, noncardiac surgery in asymptomatic patients with poor functional capacity and prior PCI or coronary artery bypass graft (new recommendation, class IIa).”
Mitral valve regurgitation. For patients undergoing scheduled noncardiac surgery, who remain symptomatic despite guideline-directed medical treatment for mitral valve regurgitation (including resynchronization and myocardial revascularization), consider a valve intervention – either transcatheter or surgical – before noncardiac surgery in eligible patients with acceptable procedural risk (new recommendation).
Cardiac implantable electronic devices (CIED). For high-risk patients with CIEDs undergoing noncardiac surgery with high probability of electromagnetic interference, a CIED checkup and necessary reprogramming immediately before the procedure should be considered (new recommendation).
Arrhythmias. “I want only to stress,” Dr. Mehilli said, “in patients with atrial fibrillation with acute or worsening hemodynamic instability undergoing noncardiac surgery, an emergency electrical cardioversion is recommended (class I).”
Peripheral artery disease (PAD) and abdominal aortic aneurysm. For these patients “we do not recommend a routine referral for a cardiac workup. But we recommend it for patients with poor functional capacity or with significant risk factors or symptoms (new recommendations).”
Chronic arterial hypertension. “We have modified the recommendation, recommending avoidance of large perioperative fluctuations in blood pressure, and we do not recommend deferring noncardiac surgery in patients with stage 1 or 2 hypertension,” she said.
Postoperative cardiovascular complications
The most frequent postoperative cardiovascular complication is PMI, Dr. Mehilli noted.
“In the BASEL-PMI registry, the incidence of this complication around intermediate or high-risk noncardiac surgery was up to 15% among patients older than 65 years or with a history of CAD or PAD, which makes this kind of complication really important to prevent, to assess, and to know how to treat.”
“It is recommended to have a high awareness for perioperative cardiovascular complications, combined with surveillance for PMI in patients undergoing intermediate- or high-risk noncardiac surgery” based on serial measurements of high-sensitivity cardiac troponin.
The guidelines define PMI as “an increase in the delta of high-sensitivity troponin more than the upper level of normal,” Dr. Mehilli said. “It’s different from the one used in a rule-in algorithm for non-STEMI acute coronary syndrome.”
Postoperative atrial fibrillation (AFib) is observed in 2%-30% of noncardiac surgery patients in different registries, particularly in patients undergoing intermediate or high-risk noncardiac surgery, she noted.
“We propose an algorithm on how to prevent and treat this complication. I want to highlight that in patients with hemodynamic unstable postoperative AF[ib], an emergency cardioversion is indicated. For the others, a rate control with the target heart rate of less than 110 beats per minute is indicated.”
In patients with postoperative AFib, long-term oral anticoagulation therapy should be considered in all patients at risk for stroke, considering the anticipated net clinical benefit of oral anticoagulation therapy as well as informed patient preference (new recommendations).
Routine use of beta-blockers to prevent postoperative AFib in patients undergoing noncardiac surgery is not recommended.
The document also covers the management of patients with kidney disease, diabetes, cancer, obesity, and COVID-19. In general, elective noncardiac surgery should be postponed after a patient has COVID-19, until he or she recovers completely, and coexisting conditions are optimized.
The guidelines are available from the ESC website in several formats: pocket guidelines, pocket guidelines smartphone app, guidelines slide set, essential messages, and the European Heart Journal article.
Noncardiac surgery risk categories
The guideline includes a table that classifies noncardiac surgeries into three groups, based on the associated 30-day risk of death, MI, or stroke:
- Low (< 1%): breast, dental, eye, thyroid, and minor gynecologic, orthopedic, and urologic surgery.
- Intermediate (1%-5%): carotid surgery, endovascular aortic aneurysm repair, gallbladder surgery, head or neck surgery, hernia repair, peripheral arterial angioplasty, renal transplant, major gynecologic, orthopedic, or neurologic (hip or spine) surgery, or urologic surgery
- High (> 5%): aortic and major vascular surgery (including aortic aneurysm), bladder removal (usually as a result of cancer), limb amputation, lung or liver transplant, pancreatic surgery, or perforated bowel repair.
The guidelines were endorsed by the European Society of Anaesthesiology and Intensive Care. The guideline authors reported numerous disclosures.
A version of this article first appeared on Medscape.com.
The European Society of Cardiology guidelines on cardiovascular assessment and management of patients undergoing noncardiac surgery have seen extensive revision since the 2014 version.
They still have the same aim – to prevent surgery-related bleeding complications, perioperative myocardial infarction/injury (PMI), stent thrombosis, acute heart failure, arrhythmias, pulmonary embolism, ischemic stroke, and cardiovascular (CV) death.
Cochairpersons Sigrun Halvorsen, MD, PhD, and Julinda Mehilli, MD, presented highlights from the guidelines at the annual congress of the European Society of Cardiology and the document was simultaneously published online in the European Heart Journal.
The document classifies noncardiac surgery into three levels of 30-day risk of CV death, MI, or stroke. Low (< 1%) risk includes eye or thyroid surgery; intermediate (1%-5%) risk includes knee or hip replacement or renal transplant; and high (> 5%) risk includes aortic aneurysm, lung transplant, or pancreatic or bladder cancer surgery (see more examples below).
It classifies patients as low risk if they are younger than 65 without CV disease or CV risk factors (smoking, hypertension, diabetes, dyslipidemia, family history); intermediate risk if they are 65 or older or have CV risk factors; and high risk if they have CVD.
In an interview, Dr. Halvorsen, professor in cardiology, University of Oslo, zeroed in on three important revisions:
First, recommendations for preoperative ECG and biomarkers are more specific, he noted.
The guidelines advise that before intermediate- or high-risk noncardiac surgery, in patients who have known CVD, CV risk factors (including age 65 or older), or symptoms suggestive of CVD:
- It is recommended to obtain a preoperative 12-lead ECG (class I).
- It is recommended to measure high-sensitivity cardiac troponin T (hs-cTn T) or high-sensitivity cardiac troponin I (hs-cTn I). It is also recommended to measure these biomarkers at 24 hours and 48 hours post surgery (class I).
- It should be considered to measure B-type natriuretic peptide or N-terminal of the prohormone BNP (NT-proBNP).
However, for low-risk patients undergoing low- and intermediate-risk noncardiac surgery, it is not recommended to routinely obtain preoperative ECG, hs-cTn T/I, or BNP/NT-proBNP concentrations (class III).
Troponins have a stronger class I recommendation, compared with the IIA recommendation for BNP, because they are useful for preoperative risk stratification and for diagnosis of PMI, Dr. Halvorsen explained. “Patients receive painkillers after surgery and may have no pain,” she noted, but they may have PMI, which has a bad prognosis.
Second, the guidelines recommend that “all patients should stop smoking 4 weeks before noncardiac surgery [class I],” she noted. Clinicians should also “measure hemoglobin, and if the patient is anemic, treat the anemia.”
Third, the sections on antithrombotic treatment have been significantly revised. “Bridging – stopping an oral antithrombotic drug and switching to a subcutaneous or IV drug – has been common,” Dr. Halvorsen said, “but recently we have new evidence that in most cases that increases the risk of bleeding.”
“We are [now] much more restrictive with respect to bridging” with unfractionated heparin or low-molecular-weight heparin, she said. “We recommend against bridging in patients with low to moderate thrombotic risk,” and bridging should only be considered in patients with mechanical prosthetic heart valves or with very high thrombotic risk.
More preoperative recommendations
In the guideline overview session at the congress, Dr. Halverson highlighted some of the new recommendations for preoperative risk assessment.
If time allows, it is recommended to optimize guideline-recommended treatment of CVD and control of CV risk factors including blood pressure, dyslipidemia, and diabetes, before noncardiac surgery (class I).
Patients commonly have “murmurs, chest pain, dyspnea, and edema that may suggest severe CVD, but may also be caused by noncardiac disease,” she noted. The guidelines state that “for patients with a newly detected murmur and symptoms or signs of CVD, transthoracic echocardiography is recommended before noncardiac surgery (class I).
“Many studies have been performed to try to find out if initiation of specific drugs before surgery could reduce the risk of complications,” Dr. Halvorsen noted. However, few have shown any benefit and “the question of presurgery initiation of beta-blockers has been greatly debated,” she said. “We have again reviewed the literature and concluded ‘Routine initiation of beta-blockers perioperatively is not recommended (class IIIA).’ “
“We adhere to the guidelines on acute and chronic coronary syndrome recommending 6-12 months of dual antiplatelet treatment as a standard before elective surgery,” she said. “However, in case of time-sensitive surgery, the duration of that treatment can be shortened down to a minimum of 1 month after elective PCI and a minimum of 3 months after PCI and ACS.”
Patients with specific types of CVD
Dr. Mehilli, a professor at Landshut-Achdorf (Germany) Hospital, highlighted some new guideline recommendations for patients who have specific types of cardiovascular disease.
Coronary artery disease (CAD). “For chronic coronary syndrome, a cardiac workup is recommended only for patients undergoing intermediate risk or high-risk noncardiac surgery.”
“Stress imaging should be considered before any high risk, noncardiac surgery in asymptomatic patients with poor functional capacity and prior PCI or coronary artery bypass graft (new recommendation, class IIa).”
Mitral valve regurgitation. For patients undergoing scheduled noncardiac surgery, who remain symptomatic despite guideline-directed medical treatment for mitral valve regurgitation (including resynchronization and myocardial revascularization), consider a valve intervention – either transcatheter or surgical – before noncardiac surgery in eligible patients with acceptable procedural risk (new recommendation).
Cardiac implantable electronic devices (CIED). For high-risk patients with CIEDs undergoing noncardiac surgery with high probability of electromagnetic interference, a CIED checkup and necessary reprogramming immediately before the procedure should be considered (new recommendation).
Arrhythmias. “I want only to stress,” Dr. Mehilli said, “in patients with atrial fibrillation with acute or worsening hemodynamic instability undergoing noncardiac surgery, an emergency electrical cardioversion is recommended (class I).”
Peripheral artery disease (PAD) and abdominal aortic aneurysm. For these patients “we do not recommend a routine referral for a cardiac workup. But we recommend it for patients with poor functional capacity or with significant risk factors or symptoms (new recommendations).”
Chronic arterial hypertension. “We have modified the recommendation, recommending avoidance of large perioperative fluctuations in blood pressure, and we do not recommend deferring noncardiac surgery in patients with stage 1 or 2 hypertension,” she said.
Postoperative cardiovascular complications
The most frequent postoperative cardiovascular complication is PMI, Dr. Mehilli noted.
“In the BASEL-PMI registry, the incidence of this complication around intermediate or high-risk noncardiac surgery was up to 15% among patients older than 65 years or with a history of CAD or PAD, which makes this kind of complication really important to prevent, to assess, and to know how to treat.”
“It is recommended to have a high awareness for perioperative cardiovascular complications, combined with surveillance for PMI in patients undergoing intermediate- or high-risk noncardiac surgery” based on serial measurements of high-sensitivity cardiac troponin.
The guidelines define PMI as “an increase in the delta of high-sensitivity troponin more than the upper level of normal,” Dr. Mehilli said. “It’s different from the one used in a rule-in algorithm for non-STEMI acute coronary syndrome.”
Postoperative atrial fibrillation (AFib) is observed in 2%-30% of noncardiac surgery patients in different registries, particularly in patients undergoing intermediate or high-risk noncardiac surgery, she noted.
“We propose an algorithm on how to prevent and treat this complication. I want to highlight that in patients with hemodynamic unstable postoperative AF[ib], an emergency cardioversion is indicated. For the others, a rate control with the target heart rate of less than 110 beats per minute is indicated.”
In patients with postoperative AFib, long-term oral anticoagulation therapy should be considered in all patients at risk for stroke, considering the anticipated net clinical benefit of oral anticoagulation therapy as well as informed patient preference (new recommendations).
Routine use of beta-blockers to prevent postoperative AFib in patients undergoing noncardiac surgery is not recommended.
The document also covers the management of patients with kidney disease, diabetes, cancer, obesity, and COVID-19. In general, elective noncardiac surgery should be postponed after a patient has COVID-19, until he or she recovers completely, and coexisting conditions are optimized.
The guidelines are available from the ESC website in several formats: pocket guidelines, pocket guidelines smartphone app, guidelines slide set, essential messages, and the European Heart Journal article.
Noncardiac surgery risk categories
The guideline includes a table that classifies noncardiac surgeries into three groups, based on the associated 30-day risk of death, MI, or stroke:
- Low (< 1%): breast, dental, eye, thyroid, and minor gynecologic, orthopedic, and urologic surgery.
- Intermediate (1%-5%): carotid surgery, endovascular aortic aneurysm repair, gallbladder surgery, head or neck surgery, hernia repair, peripheral arterial angioplasty, renal transplant, major gynecologic, orthopedic, or neurologic (hip or spine) surgery, or urologic surgery
- High (> 5%): aortic and major vascular surgery (including aortic aneurysm), bladder removal (usually as a result of cancer), limb amputation, lung or liver transplant, pancreatic surgery, or perforated bowel repair.
The guidelines were endorsed by the European Society of Anaesthesiology and Intensive Care. The guideline authors reported numerous disclosures.
A version of this article first appeared on Medscape.com.
The European Society of Cardiology guidelines on cardiovascular assessment and management of patients undergoing noncardiac surgery have seen extensive revision since the 2014 version.
They still have the same aim – to prevent surgery-related bleeding complications, perioperative myocardial infarction/injury (PMI), stent thrombosis, acute heart failure, arrhythmias, pulmonary embolism, ischemic stroke, and cardiovascular (CV) death.
Cochairpersons Sigrun Halvorsen, MD, PhD, and Julinda Mehilli, MD, presented highlights from the guidelines at the annual congress of the European Society of Cardiology and the document was simultaneously published online in the European Heart Journal.
The document classifies noncardiac surgery into three levels of 30-day risk of CV death, MI, or stroke. Low (< 1%) risk includes eye or thyroid surgery; intermediate (1%-5%) risk includes knee or hip replacement or renal transplant; and high (> 5%) risk includes aortic aneurysm, lung transplant, or pancreatic or bladder cancer surgery (see more examples below).
It classifies patients as low risk if they are younger than 65 without CV disease or CV risk factors (smoking, hypertension, diabetes, dyslipidemia, family history); intermediate risk if they are 65 or older or have CV risk factors; and high risk if they have CVD.
In an interview, Dr. Halvorsen, professor in cardiology, University of Oslo, zeroed in on three important revisions:
First, recommendations for preoperative ECG and biomarkers are more specific, he noted.
The guidelines advise that before intermediate- or high-risk noncardiac surgery, in patients who have known CVD, CV risk factors (including age 65 or older), or symptoms suggestive of CVD:
- It is recommended to obtain a preoperative 12-lead ECG (class I).
- It is recommended to measure high-sensitivity cardiac troponin T (hs-cTn T) or high-sensitivity cardiac troponin I (hs-cTn I). It is also recommended to measure these biomarkers at 24 hours and 48 hours post surgery (class I).
- It should be considered to measure B-type natriuretic peptide or N-terminal of the prohormone BNP (NT-proBNP).
However, for low-risk patients undergoing low- and intermediate-risk noncardiac surgery, it is not recommended to routinely obtain preoperative ECG, hs-cTn T/I, or BNP/NT-proBNP concentrations (class III).
Troponins have a stronger class I recommendation, compared with the IIA recommendation for BNP, because they are useful for preoperative risk stratification and for diagnosis of PMI, Dr. Halvorsen explained. “Patients receive painkillers after surgery and may have no pain,” she noted, but they may have PMI, which has a bad prognosis.
Second, the guidelines recommend that “all patients should stop smoking 4 weeks before noncardiac surgery [class I],” she noted. Clinicians should also “measure hemoglobin, and if the patient is anemic, treat the anemia.”
Third, the sections on antithrombotic treatment have been significantly revised. “Bridging – stopping an oral antithrombotic drug and switching to a subcutaneous or IV drug – has been common,” Dr. Halvorsen said, “but recently we have new evidence that in most cases that increases the risk of bleeding.”
“We are [now] much more restrictive with respect to bridging” with unfractionated heparin or low-molecular-weight heparin, she said. “We recommend against bridging in patients with low to moderate thrombotic risk,” and bridging should only be considered in patients with mechanical prosthetic heart valves or with very high thrombotic risk.
More preoperative recommendations
In the guideline overview session at the congress, Dr. Halverson highlighted some of the new recommendations for preoperative risk assessment.
If time allows, it is recommended to optimize guideline-recommended treatment of CVD and control of CV risk factors including blood pressure, dyslipidemia, and diabetes, before noncardiac surgery (class I).
Patients commonly have “murmurs, chest pain, dyspnea, and edema that may suggest severe CVD, but may also be caused by noncardiac disease,” she noted. The guidelines state that “for patients with a newly detected murmur and symptoms or signs of CVD, transthoracic echocardiography is recommended before noncardiac surgery (class I).
“Many studies have been performed to try to find out if initiation of specific drugs before surgery could reduce the risk of complications,” Dr. Halvorsen noted. However, few have shown any benefit and “the question of presurgery initiation of beta-blockers has been greatly debated,” she said. “We have again reviewed the literature and concluded ‘Routine initiation of beta-blockers perioperatively is not recommended (class IIIA).’ “
“We adhere to the guidelines on acute and chronic coronary syndrome recommending 6-12 months of dual antiplatelet treatment as a standard before elective surgery,” she said. “However, in case of time-sensitive surgery, the duration of that treatment can be shortened down to a minimum of 1 month after elective PCI and a minimum of 3 months after PCI and ACS.”
Patients with specific types of CVD
Dr. Mehilli, a professor at Landshut-Achdorf (Germany) Hospital, highlighted some new guideline recommendations for patients who have specific types of cardiovascular disease.
Coronary artery disease (CAD). “For chronic coronary syndrome, a cardiac workup is recommended only for patients undergoing intermediate risk or high-risk noncardiac surgery.”
“Stress imaging should be considered before any high risk, noncardiac surgery in asymptomatic patients with poor functional capacity and prior PCI or coronary artery bypass graft (new recommendation, class IIa).”
Mitral valve regurgitation. For patients undergoing scheduled noncardiac surgery, who remain symptomatic despite guideline-directed medical treatment for mitral valve regurgitation (including resynchronization and myocardial revascularization), consider a valve intervention – either transcatheter or surgical – before noncardiac surgery in eligible patients with acceptable procedural risk (new recommendation).
Cardiac implantable electronic devices (CIED). For high-risk patients with CIEDs undergoing noncardiac surgery with high probability of electromagnetic interference, a CIED checkup and necessary reprogramming immediately before the procedure should be considered (new recommendation).
Arrhythmias. “I want only to stress,” Dr. Mehilli said, “in patients with atrial fibrillation with acute or worsening hemodynamic instability undergoing noncardiac surgery, an emergency electrical cardioversion is recommended (class I).”
Peripheral artery disease (PAD) and abdominal aortic aneurysm. For these patients “we do not recommend a routine referral for a cardiac workup. But we recommend it for patients with poor functional capacity or with significant risk factors or symptoms (new recommendations).”
Chronic arterial hypertension. “We have modified the recommendation, recommending avoidance of large perioperative fluctuations in blood pressure, and we do not recommend deferring noncardiac surgery in patients with stage 1 or 2 hypertension,” she said.
Postoperative cardiovascular complications
The most frequent postoperative cardiovascular complication is PMI, Dr. Mehilli noted.
“In the BASEL-PMI registry, the incidence of this complication around intermediate or high-risk noncardiac surgery was up to 15% among patients older than 65 years or with a history of CAD or PAD, which makes this kind of complication really important to prevent, to assess, and to know how to treat.”
“It is recommended to have a high awareness for perioperative cardiovascular complications, combined with surveillance for PMI in patients undergoing intermediate- or high-risk noncardiac surgery” based on serial measurements of high-sensitivity cardiac troponin.
The guidelines define PMI as “an increase in the delta of high-sensitivity troponin more than the upper level of normal,” Dr. Mehilli said. “It’s different from the one used in a rule-in algorithm for non-STEMI acute coronary syndrome.”
Postoperative atrial fibrillation (AFib) is observed in 2%-30% of noncardiac surgery patients in different registries, particularly in patients undergoing intermediate or high-risk noncardiac surgery, she noted.
“We propose an algorithm on how to prevent and treat this complication. I want to highlight that in patients with hemodynamic unstable postoperative AF[ib], an emergency cardioversion is indicated. For the others, a rate control with the target heart rate of less than 110 beats per minute is indicated.”
In patients with postoperative AFib, long-term oral anticoagulation therapy should be considered in all patients at risk for stroke, considering the anticipated net clinical benefit of oral anticoagulation therapy as well as informed patient preference (new recommendations).
Routine use of beta-blockers to prevent postoperative AFib in patients undergoing noncardiac surgery is not recommended.
The document also covers the management of patients with kidney disease, diabetes, cancer, obesity, and COVID-19. In general, elective noncardiac surgery should be postponed after a patient has COVID-19, until he or she recovers completely, and coexisting conditions are optimized.
The guidelines are available from the ESC website in several formats: pocket guidelines, pocket guidelines smartphone app, guidelines slide set, essential messages, and the European Heart Journal article.
Noncardiac surgery risk categories
The guideline includes a table that classifies noncardiac surgeries into three groups, based on the associated 30-day risk of death, MI, or stroke:
- Low (< 1%): breast, dental, eye, thyroid, and minor gynecologic, orthopedic, and urologic surgery.
- Intermediate (1%-5%): carotid surgery, endovascular aortic aneurysm repair, gallbladder surgery, head or neck surgery, hernia repair, peripheral arterial angioplasty, renal transplant, major gynecologic, orthopedic, or neurologic (hip or spine) surgery, or urologic surgery
- High (> 5%): aortic and major vascular surgery (including aortic aneurysm), bladder removal (usually as a result of cancer), limb amputation, lung or liver transplant, pancreatic surgery, or perforated bowel repair.
The guidelines were endorsed by the European Society of Anaesthesiology and Intensive Care. The guideline authors reported numerous disclosures.
A version of this article first appeared on Medscape.com.
FROM ESC CONGRESS 2022