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Mental illness tied to increased dementia risk
Results of a large, longitudinal, population-based study show that individuals hospitalized for a mental health disorder had a fourfold increased relative risk (RR) for developing dementia, compared with those who were not hospitalized with a mental illness.
In addition, those with dementia plus a mental disorder developed dementia almost 6 years earlier than those without a mental illness.
The findings were consistent among men and women, in patients with early- and late-onset dementia, in those with Alzheimer’s and non-Alzheimer’s dementia, and across all mental health disorders – and remained so after accounting for pre-existing physical illness and socioeconomic factors.
“Dementia is not typically treated until later in life, but our study suggests that we need to be thinking about dementia prevention much earlier in the life course,” study investigator Leah Richmond-Rakerd, PhD, assistant professor, department of psychology, University of Michigan, said in an interview.
“Supporting young people’s mental health could be a window of opportunity to help reduce the burden of dementia in older adults,” she said.
The findings were published online Feb. 16.
Underappreciated risk factor
“Recognition of the outsized influence of dementia on later-life functioning has fueled research into modifiable risk factors and prevention targets,” the investigators write.
Previous research suggests mental disorders may “comprise an underappreciated category of modifiable risk factors.” However, those studies focused primarily on midlife and older individuals, not on capturing mental disorders during young adulthood, which is the time of “peak prevalence,” they add. In addition, most studies have not explored the full range of mental disorders.
Dr. Richmond-Rakerd noted that it is well known that mental health disorders peak in adolescence and young adulthood – and are treatable.
“If the same people who have mental disorders when they are young tend to develop dementia when they are older, that would mean that preventing mental health problems in younger people might reduce or delay the burden of dementia in older people,” she said.
The investigators assessed records from the New Zealand Integrated Data Infrastructure, which is a de-identified register that includes the entire New Zealand population. They also examined information about hospitalizations and diagnoses from records kept by the New Zealand Ministry of Health.
The researchers followed 1,711,386 individuals born between 1928 and 1967 (50.6% men, aged 21 to 60 years at baseline) for 30 years. The population was subdivided into age groups based on birth years: 1928-1937 (14.8%), 1938-1947 (20.85%), 1948-1957 (29.35%), and 1958-1967 (35.1%).
Earlier onset
During the study period, 3.8% of individuals were identified as having a mental disorder, and 2% were identified as having dementia. Similar percentages of men and women had a mental disorder, and similar percentages had dementia.
Dementia was “over-represented” among participants with versus without a mental disorder (6.1% vs. 1.8%). This finding held across all age groups.
Those diagnosed with a mental disorder were also more likely to develop dementia, compared with their peers without a mental disorder (RR, 3.51; 95% confidence interval, 3.39-3.64), which is a larger association than that between physical diseases and dementia (RR, 1.19; 95% CI, 1.16-1.21).
These associations were present in both sexes and in all age groups, although the associations were stronger in more recently born cohorts.
A sixfold higher risk for dementia remained even after adjusting for pre-existing physical illnesses (HR, 6.49; 95% CI, 6.25-6.73); and the elevated risk was evident across different lengths of follow-up from the index mental disorder.
When the researchers focused specifically on individuals diagnosed with dementia, they found that those diagnosed with a mental disorder developed dementia a mean of 5.60 years earlier than those without a mental disorder diagnosis – an association observed across both sexes and all age groups.
“Individuals diagnosed with psychotic, substance use, mood, neurotic, and all other mental disorders and who engaged in self-harm were all more likely than those without a mental disorder to be diagnosed with subsequent dementia, even after accounting for their physical disease histories,” the investigators write.
Although there was a link between mental disorders in both Alzheimer’s and non-Alzheimer’s dementias, the association was larger in non-Alzheimer’s.
The researchers note that the study has several limitations, including the fact that it was conducted in New Zealand and therefore the results may not be generalizable to other regions. In addition, inpatient hospital records do not capture less severe mental disorder cases treated in the outpatient setting.
Dr. Richmond-Rakerd suggested several potential mechanisms that could account for the link between mental illness and dementia, including poor lifestyle choices and metabolic side effects associated with some psychiatric medications.
“There could also be shared risk factors for both mental disorders and dementia, such as shared genetics, or individuals may experience a lifelong brain vulnerability that shows up as mental health problems earlier in life and shows up as dementia later in life,” she said.
An important risk factor
Commenting for this article, Ken Duckworth, MD, chief medical officer of the National Alliance on Mental Illness, said a major strength of the study was its longitudinal scope and large population size.
He described the study as allowing clinicians to “watch the movie,” as opposed to looking at a “snapshot” of data.
“Although you can learn things from snapshots, a large, comprehensive public health system looking at 30 years of claims – something not possible in the U.S. because of our more fragmented health care system – offers more insight,” said Dr. Duckworth, who was not involved with the research.
The investigators are “painting a picture of a correlation of risk, and to me, that’s the beginning of further inquiry,” he added. “Would preventive efforts targeting dementia, such as exercise and socialization, be helpful? It’s a great study that raises these interesting questions.”
Also commenting in an interview, Claire Sexton, DPhil, director of scientific programs and outreach at the Alzheimer’s Association, said the study “adds a wealth of data to our understanding” of mental disorders as a dementia risk factor.
However, the study was observational, so “the findings cannot imply causation, [and just] because someone has depression, that does not mean they will go on to develop Alzheimer’s,” said Dr. Sexton, who also was not involved with the research.
Still, “these data support the idea that taking care of one’s mental health is incredibly important for overall wellbeing. For providers, it’s important to have mental health evaluation be a part of your patient’s regular checkups,” she added.
Dr. Richmond-Rakerd noted that even if mental health conditions are not a causal risk factor for dementia, “the presence of a mental health problem is still an important indicator of risk. Mental health providers may wish to target other risk factors for dementia that are more common in individuals with mental health conditions, such as social disconnection.”
The study was funded by grants from the National Institute on Aging, the U.K. Medical Research Council, the National Institute of Child Health and Development through the Duke Population Research Center, and the National Institute on Aging through the Center for Advancing Sociodemographic and Economic Study of Alzheimer’s Disease and Related Dementias. Dr. Richmond-Rakerd reports no relevant financial relationships. The other investigators’ disclosures are listed in the original article. Dr. Sexton and Dr. Duckworth report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Results of a large, longitudinal, population-based study show that individuals hospitalized for a mental health disorder had a fourfold increased relative risk (RR) for developing dementia, compared with those who were not hospitalized with a mental illness.
In addition, those with dementia plus a mental disorder developed dementia almost 6 years earlier than those without a mental illness.
The findings were consistent among men and women, in patients with early- and late-onset dementia, in those with Alzheimer’s and non-Alzheimer’s dementia, and across all mental health disorders – and remained so after accounting for pre-existing physical illness and socioeconomic factors.
“Dementia is not typically treated until later in life, but our study suggests that we need to be thinking about dementia prevention much earlier in the life course,” study investigator Leah Richmond-Rakerd, PhD, assistant professor, department of psychology, University of Michigan, said in an interview.
“Supporting young people’s mental health could be a window of opportunity to help reduce the burden of dementia in older adults,” she said.
The findings were published online Feb. 16.
Underappreciated risk factor
“Recognition of the outsized influence of dementia on later-life functioning has fueled research into modifiable risk factors and prevention targets,” the investigators write.
Previous research suggests mental disorders may “comprise an underappreciated category of modifiable risk factors.” However, those studies focused primarily on midlife and older individuals, not on capturing mental disorders during young adulthood, which is the time of “peak prevalence,” they add. In addition, most studies have not explored the full range of mental disorders.
Dr. Richmond-Rakerd noted that it is well known that mental health disorders peak in adolescence and young adulthood – and are treatable.
“If the same people who have mental disorders when they are young tend to develop dementia when they are older, that would mean that preventing mental health problems in younger people might reduce or delay the burden of dementia in older people,” she said.
The investigators assessed records from the New Zealand Integrated Data Infrastructure, which is a de-identified register that includes the entire New Zealand population. They also examined information about hospitalizations and diagnoses from records kept by the New Zealand Ministry of Health.
The researchers followed 1,711,386 individuals born between 1928 and 1967 (50.6% men, aged 21 to 60 years at baseline) for 30 years. The population was subdivided into age groups based on birth years: 1928-1937 (14.8%), 1938-1947 (20.85%), 1948-1957 (29.35%), and 1958-1967 (35.1%).
Earlier onset
During the study period, 3.8% of individuals were identified as having a mental disorder, and 2% were identified as having dementia. Similar percentages of men and women had a mental disorder, and similar percentages had dementia.
Dementia was “over-represented” among participants with versus without a mental disorder (6.1% vs. 1.8%). This finding held across all age groups.
Those diagnosed with a mental disorder were also more likely to develop dementia, compared with their peers without a mental disorder (RR, 3.51; 95% confidence interval, 3.39-3.64), which is a larger association than that between physical diseases and dementia (RR, 1.19; 95% CI, 1.16-1.21).
These associations were present in both sexes and in all age groups, although the associations were stronger in more recently born cohorts.
A sixfold higher risk for dementia remained even after adjusting for pre-existing physical illnesses (HR, 6.49; 95% CI, 6.25-6.73); and the elevated risk was evident across different lengths of follow-up from the index mental disorder.
When the researchers focused specifically on individuals diagnosed with dementia, they found that those diagnosed with a mental disorder developed dementia a mean of 5.60 years earlier than those without a mental disorder diagnosis – an association observed across both sexes and all age groups.
“Individuals diagnosed with psychotic, substance use, mood, neurotic, and all other mental disorders and who engaged in self-harm were all more likely than those without a mental disorder to be diagnosed with subsequent dementia, even after accounting for their physical disease histories,” the investigators write.
Although there was a link between mental disorders in both Alzheimer’s and non-Alzheimer’s dementias, the association was larger in non-Alzheimer’s.
The researchers note that the study has several limitations, including the fact that it was conducted in New Zealand and therefore the results may not be generalizable to other regions. In addition, inpatient hospital records do not capture less severe mental disorder cases treated in the outpatient setting.
Dr. Richmond-Rakerd suggested several potential mechanisms that could account for the link between mental illness and dementia, including poor lifestyle choices and metabolic side effects associated with some psychiatric medications.
“There could also be shared risk factors for both mental disorders and dementia, such as shared genetics, or individuals may experience a lifelong brain vulnerability that shows up as mental health problems earlier in life and shows up as dementia later in life,” she said.
An important risk factor
Commenting for this article, Ken Duckworth, MD, chief medical officer of the National Alliance on Mental Illness, said a major strength of the study was its longitudinal scope and large population size.
He described the study as allowing clinicians to “watch the movie,” as opposed to looking at a “snapshot” of data.
“Although you can learn things from snapshots, a large, comprehensive public health system looking at 30 years of claims – something not possible in the U.S. because of our more fragmented health care system – offers more insight,” said Dr. Duckworth, who was not involved with the research.
The investigators are “painting a picture of a correlation of risk, and to me, that’s the beginning of further inquiry,” he added. “Would preventive efforts targeting dementia, such as exercise and socialization, be helpful? It’s a great study that raises these interesting questions.”
Also commenting in an interview, Claire Sexton, DPhil, director of scientific programs and outreach at the Alzheimer’s Association, said the study “adds a wealth of data to our understanding” of mental disorders as a dementia risk factor.
However, the study was observational, so “the findings cannot imply causation, [and just] because someone has depression, that does not mean they will go on to develop Alzheimer’s,” said Dr. Sexton, who also was not involved with the research.
Still, “these data support the idea that taking care of one’s mental health is incredibly important for overall wellbeing. For providers, it’s important to have mental health evaluation be a part of your patient’s regular checkups,” she added.
Dr. Richmond-Rakerd noted that even if mental health conditions are not a causal risk factor for dementia, “the presence of a mental health problem is still an important indicator of risk. Mental health providers may wish to target other risk factors for dementia that are more common in individuals with mental health conditions, such as social disconnection.”
The study was funded by grants from the National Institute on Aging, the U.K. Medical Research Council, the National Institute of Child Health and Development through the Duke Population Research Center, and the National Institute on Aging through the Center for Advancing Sociodemographic and Economic Study of Alzheimer’s Disease and Related Dementias. Dr. Richmond-Rakerd reports no relevant financial relationships. The other investigators’ disclosures are listed in the original article. Dr. Sexton and Dr. Duckworth report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Results of a large, longitudinal, population-based study show that individuals hospitalized for a mental health disorder had a fourfold increased relative risk (RR) for developing dementia, compared with those who were not hospitalized with a mental illness.
In addition, those with dementia plus a mental disorder developed dementia almost 6 years earlier than those without a mental illness.
The findings were consistent among men and women, in patients with early- and late-onset dementia, in those with Alzheimer’s and non-Alzheimer’s dementia, and across all mental health disorders – and remained so after accounting for pre-existing physical illness and socioeconomic factors.
“Dementia is not typically treated until later in life, but our study suggests that we need to be thinking about dementia prevention much earlier in the life course,” study investigator Leah Richmond-Rakerd, PhD, assistant professor, department of psychology, University of Michigan, said in an interview.
“Supporting young people’s mental health could be a window of opportunity to help reduce the burden of dementia in older adults,” she said.
The findings were published online Feb. 16.
Underappreciated risk factor
“Recognition of the outsized influence of dementia on later-life functioning has fueled research into modifiable risk factors and prevention targets,” the investigators write.
Previous research suggests mental disorders may “comprise an underappreciated category of modifiable risk factors.” However, those studies focused primarily on midlife and older individuals, not on capturing mental disorders during young adulthood, which is the time of “peak prevalence,” they add. In addition, most studies have not explored the full range of mental disorders.
Dr. Richmond-Rakerd noted that it is well known that mental health disorders peak in adolescence and young adulthood – and are treatable.
“If the same people who have mental disorders when they are young tend to develop dementia when they are older, that would mean that preventing mental health problems in younger people might reduce or delay the burden of dementia in older people,” she said.
The investigators assessed records from the New Zealand Integrated Data Infrastructure, which is a de-identified register that includes the entire New Zealand population. They also examined information about hospitalizations and diagnoses from records kept by the New Zealand Ministry of Health.
The researchers followed 1,711,386 individuals born between 1928 and 1967 (50.6% men, aged 21 to 60 years at baseline) for 30 years. The population was subdivided into age groups based on birth years: 1928-1937 (14.8%), 1938-1947 (20.85%), 1948-1957 (29.35%), and 1958-1967 (35.1%).
Earlier onset
During the study period, 3.8% of individuals were identified as having a mental disorder, and 2% were identified as having dementia. Similar percentages of men and women had a mental disorder, and similar percentages had dementia.
Dementia was “over-represented” among participants with versus without a mental disorder (6.1% vs. 1.8%). This finding held across all age groups.
Those diagnosed with a mental disorder were also more likely to develop dementia, compared with their peers without a mental disorder (RR, 3.51; 95% confidence interval, 3.39-3.64), which is a larger association than that between physical diseases and dementia (RR, 1.19; 95% CI, 1.16-1.21).
These associations were present in both sexes and in all age groups, although the associations were stronger in more recently born cohorts.
A sixfold higher risk for dementia remained even after adjusting for pre-existing physical illnesses (HR, 6.49; 95% CI, 6.25-6.73); and the elevated risk was evident across different lengths of follow-up from the index mental disorder.
When the researchers focused specifically on individuals diagnosed with dementia, they found that those diagnosed with a mental disorder developed dementia a mean of 5.60 years earlier than those without a mental disorder diagnosis – an association observed across both sexes and all age groups.
“Individuals diagnosed with psychotic, substance use, mood, neurotic, and all other mental disorders and who engaged in self-harm were all more likely than those without a mental disorder to be diagnosed with subsequent dementia, even after accounting for their physical disease histories,” the investigators write.
Although there was a link between mental disorders in both Alzheimer’s and non-Alzheimer’s dementias, the association was larger in non-Alzheimer’s.
The researchers note that the study has several limitations, including the fact that it was conducted in New Zealand and therefore the results may not be generalizable to other regions. In addition, inpatient hospital records do not capture less severe mental disorder cases treated in the outpatient setting.
Dr. Richmond-Rakerd suggested several potential mechanisms that could account for the link between mental illness and dementia, including poor lifestyle choices and metabolic side effects associated with some psychiatric medications.
“There could also be shared risk factors for both mental disorders and dementia, such as shared genetics, or individuals may experience a lifelong brain vulnerability that shows up as mental health problems earlier in life and shows up as dementia later in life,” she said.
An important risk factor
Commenting for this article, Ken Duckworth, MD, chief medical officer of the National Alliance on Mental Illness, said a major strength of the study was its longitudinal scope and large population size.
He described the study as allowing clinicians to “watch the movie,” as opposed to looking at a “snapshot” of data.
“Although you can learn things from snapshots, a large, comprehensive public health system looking at 30 years of claims – something not possible in the U.S. because of our more fragmented health care system – offers more insight,” said Dr. Duckworth, who was not involved with the research.
The investigators are “painting a picture of a correlation of risk, and to me, that’s the beginning of further inquiry,” he added. “Would preventive efforts targeting dementia, such as exercise and socialization, be helpful? It’s a great study that raises these interesting questions.”
Also commenting in an interview, Claire Sexton, DPhil, director of scientific programs and outreach at the Alzheimer’s Association, said the study “adds a wealth of data to our understanding” of mental disorders as a dementia risk factor.
However, the study was observational, so “the findings cannot imply causation, [and just] because someone has depression, that does not mean they will go on to develop Alzheimer’s,” said Dr. Sexton, who also was not involved with the research.
Still, “these data support the idea that taking care of one’s mental health is incredibly important for overall wellbeing. For providers, it’s important to have mental health evaluation be a part of your patient’s regular checkups,” she added.
Dr. Richmond-Rakerd noted that even if mental health conditions are not a causal risk factor for dementia, “the presence of a mental health problem is still an important indicator of risk. Mental health providers may wish to target other risk factors for dementia that are more common in individuals with mental health conditions, such as social disconnection.”
The study was funded by grants from the National Institute on Aging, the U.K. Medical Research Council, the National Institute of Child Health and Development through the Duke Population Research Center, and the National Institute on Aging through the Center for Advancing Sociodemographic and Economic Study of Alzheimer’s Disease and Related Dementias. Dr. Richmond-Rakerd reports no relevant financial relationships. The other investigators’ disclosures are listed in the original article. Dr. Sexton and Dr. Duckworth report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA PSYCHIATRY
NY radiation oncologist loses license, poses ‘potential danger’
The state Board for Professional Medical Conduct has revoked the medical license of Won Sam Yi, MD, following a lengthy review of the care he provided to seven cancer patients; six of them died.
“He is a danger to potential new patients should he be reinstated as a radiation oncologist,” board members wrote, according to a news report in the Buffalo News.
Dr. Yi’s lawyer said that he is appealing the decision.
Dr. Yi was the former CEO of the now-defunct private cancer practice CCS Oncology, located in western New York.
In 2018, the state health department brought numerous charges of professional misconduct against Dr. Yi, including charges that he had failed to “account for prior doses of radiotherapy” as well as exceeding “appropriate tissue tolerances” during the treatment.
Now, the state’s Board for Professional Medical Conduct has upheld nearly all of the departmental charges that had been levied against him, and also found that Dr. Yi failed to take responsibility or show contrition for his treatment decisions.
However, whistleblower claims from a former CSS Oncology employee were dismissed.
Troubled history
CCS Oncology was once one of the largest private cancer practices in Erie and Niagara counties, both in the Buffalo metropolitan area.
Dr. Yi purchased CCS Oncology in 2008 and was its sole shareholder, and in 2012 he also acquired CCS Medical. As of 2016, the practices provided care to about 30% of cancer patients in the region. CCS also began acquiring other practices as it expanded into noncancer specialties, including primary care.
However, CCS began to struggle financially in late 2016, when health insurance provider Independent Health announced it was removing CCS Oncology from its network, and several vendors and lenders subsequently sued CCS and Dr. Yi for nonpayment.
The announcement from Independent Health was “financially devastating to CCS,” and also was “the direct cause” of the practice defaulting on its Bank of America loan and of the practice’s inability to pay not only its vendors but state and federal tax agencies, the Buffalo News reported. As a result, several vendors and lenders had sued CCS and Dr. Yi for nonpayment.
The FBI raided numerous CCS locations in March 2018, seizing financial and other data as part of an investigation into possible Medicare billing fraud. The following month, CCS filed for Chapter 11 bankruptcy, citing it owed millions of dollars to Bank of America and other creditors. Shortly afterward, the practice closed.
Medical misconduct
The state’s charges of professional misconduct accused Dr. Yi of “gross negligence,” “gross incompetence,” and several other cases of misconduct in treating seven patients between 2009 and 2013 at various CCS locations. The patients ranged in age from 27 to 72. Six of the seven patients died.
In one case, Dr. Yi was accused of providing whole-brain radiation therapy to a 43-year-old woman for about 6 weeks in 2012, but the treatment was “contrary to medical indications” and did not take into account prior doses of such treatment. The patient died in December of that year, and the board concluded that Dr. Yi had improperly treated her with a high dose of radiation that was intended to cure her cancer even though she was at a stage where her disease was incurable.
The state board eventually concluded that for all but one of the patients in question, Dr. Yi was guilty of misconduct in his treatment decisions. They wrote that Dr. Yi had frequently administered radiation doses without taking into account how much radiation therapy the patients had received previously and without considering the risk of serious complications for them.
Dr. Yi plans to appeal the board’s decision in state court, according to his attorney, Anthony Scher.
“Dr Yi has treated over 10,000 patients in his career,” Mr. Scher told the Buffalo News. “These handful of cases don’t represent the thousands of success stories that he’s had.”
A version of this article first appeared on Medscape.com.
The state Board for Professional Medical Conduct has revoked the medical license of Won Sam Yi, MD, following a lengthy review of the care he provided to seven cancer patients; six of them died.
“He is a danger to potential new patients should he be reinstated as a radiation oncologist,” board members wrote, according to a news report in the Buffalo News.
Dr. Yi’s lawyer said that he is appealing the decision.
Dr. Yi was the former CEO of the now-defunct private cancer practice CCS Oncology, located in western New York.
In 2018, the state health department brought numerous charges of professional misconduct against Dr. Yi, including charges that he had failed to “account for prior doses of radiotherapy” as well as exceeding “appropriate tissue tolerances” during the treatment.
Now, the state’s Board for Professional Medical Conduct has upheld nearly all of the departmental charges that had been levied against him, and also found that Dr. Yi failed to take responsibility or show contrition for his treatment decisions.
However, whistleblower claims from a former CSS Oncology employee were dismissed.
Troubled history
CCS Oncology was once one of the largest private cancer practices in Erie and Niagara counties, both in the Buffalo metropolitan area.
Dr. Yi purchased CCS Oncology in 2008 and was its sole shareholder, and in 2012 he also acquired CCS Medical. As of 2016, the practices provided care to about 30% of cancer patients in the region. CCS also began acquiring other practices as it expanded into noncancer specialties, including primary care.
However, CCS began to struggle financially in late 2016, when health insurance provider Independent Health announced it was removing CCS Oncology from its network, and several vendors and lenders subsequently sued CCS and Dr. Yi for nonpayment.
The announcement from Independent Health was “financially devastating to CCS,” and also was “the direct cause” of the practice defaulting on its Bank of America loan and of the practice’s inability to pay not only its vendors but state and federal tax agencies, the Buffalo News reported. As a result, several vendors and lenders had sued CCS and Dr. Yi for nonpayment.
The FBI raided numerous CCS locations in March 2018, seizing financial and other data as part of an investigation into possible Medicare billing fraud. The following month, CCS filed for Chapter 11 bankruptcy, citing it owed millions of dollars to Bank of America and other creditors. Shortly afterward, the practice closed.
Medical misconduct
The state’s charges of professional misconduct accused Dr. Yi of “gross negligence,” “gross incompetence,” and several other cases of misconduct in treating seven patients between 2009 and 2013 at various CCS locations. The patients ranged in age from 27 to 72. Six of the seven patients died.
In one case, Dr. Yi was accused of providing whole-brain radiation therapy to a 43-year-old woman for about 6 weeks in 2012, but the treatment was “contrary to medical indications” and did not take into account prior doses of such treatment. The patient died in December of that year, and the board concluded that Dr. Yi had improperly treated her with a high dose of radiation that was intended to cure her cancer even though she was at a stage where her disease was incurable.
The state board eventually concluded that for all but one of the patients in question, Dr. Yi was guilty of misconduct in his treatment decisions. They wrote that Dr. Yi had frequently administered radiation doses without taking into account how much radiation therapy the patients had received previously and without considering the risk of serious complications for them.
Dr. Yi plans to appeal the board’s decision in state court, according to his attorney, Anthony Scher.
“Dr Yi has treated over 10,000 patients in his career,” Mr. Scher told the Buffalo News. “These handful of cases don’t represent the thousands of success stories that he’s had.”
A version of this article first appeared on Medscape.com.
The state Board for Professional Medical Conduct has revoked the medical license of Won Sam Yi, MD, following a lengthy review of the care he provided to seven cancer patients; six of them died.
“He is a danger to potential new patients should he be reinstated as a radiation oncologist,” board members wrote, according to a news report in the Buffalo News.
Dr. Yi’s lawyer said that he is appealing the decision.
Dr. Yi was the former CEO of the now-defunct private cancer practice CCS Oncology, located in western New York.
In 2018, the state health department brought numerous charges of professional misconduct against Dr. Yi, including charges that he had failed to “account for prior doses of radiotherapy” as well as exceeding “appropriate tissue tolerances” during the treatment.
Now, the state’s Board for Professional Medical Conduct has upheld nearly all of the departmental charges that had been levied against him, and also found that Dr. Yi failed to take responsibility or show contrition for his treatment decisions.
However, whistleblower claims from a former CSS Oncology employee were dismissed.
Troubled history
CCS Oncology was once one of the largest private cancer practices in Erie and Niagara counties, both in the Buffalo metropolitan area.
Dr. Yi purchased CCS Oncology in 2008 and was its sole shareholder, and in 2012 he also acquired CCS Medical. As of 2016, the practices provided care to about 30% of cancer patients in the region. CCS also began acquiring other practices as it expanded into noncancer specialties, including primary care.
However, CCS began to struggle financially in late 2016, when health insurance provider Independent Health announced it was removing CCS Oncology from its network, and several vendors and lenders subsequently sued CCS and Dr. Yi for nonpayment.
The announcement from Independent Health was “financially devastating to CCS,” and also was “the direct cause” of the practice defaulting on its Bank of America loan and of the practice’s inability to pay not only its vendors but state and federal tax agencies, the Buffalo News reported. As a result, several vendors and lenders had sued CCS and Dr. Yi for nonpayment.
The FBI raided numerous CCS locations in March 2018, seizing financial and other data as part of an investigation into possible Medicare billing fraud. The following month, CCS filed for Chapter 11 bankruptcy, citing it owed millions of dollars to Bank of America and other creditors. Shortly afterward, the practice closed.
Medical misconduct
The state’s charges of professional misconduct accused Dr. Yi of “gross negligence,” “gross incompetence,” and several other cases of misconduct in treating seven patients between 2009 and 2013 at various CCS locations. The patients ranged in age from 27 to 72. Six of the seven patients died.
In one case, Dr. Yi was accused of providing whole-brain radiation therapy to a 43-year-old woman for about 6 weeks in 2012, but the treatment was “contrary to medical indications” and did not take into account prior doses of such treatment. The patient died in December of that year, and the board concluded that Dr. Yi had improperly treated her with a high dose of radiation that was intended to cure her cancer even though she was at a stage where her disease was incurable.
The state board eventually concluded that for all but one of the patients in question, Dr. Yi was guilty of misconduct in his treatment decisions. They wrote that Dr. Yi had frequently administered radiation doses without taking into account how much radiation therapy the patients had received previously and without considering the risk of serious complications for them.
Dr. Yi plans to appeal the board’s decision in state court, according to his attorney, Anthony Scher.
“Dr Yi has treated over 10,000 patients in his career,” Mr. Scher told the Buffalo News. “These handful of cases don’t represent the thousands of success stories that he’s had.”
A version of this article first appeared on Medscape.com.
Why pregnant people were left behind while vaccines moved at ‘warp speed’ to help the masses
Kia Slade was 7 months pregnant, unvaccinated, and fighting for breath, her oxygen levels plummeting, when her son came into the world last May.
A severe case of COVID-19 pneumonia had left Ms. Slade delirious. When the intensive care team tried to place an oxygen mask on her face, she snatched it away, she recalled. Her baby’s heart rate began to drop.
Ms. Slade’s doctor performed an emergency cesarean section at her bedside in the intensive care unit, delivering baby Tristan 10 weeks early. He weighed just 2 pounds, 14 ounces, about half the size of small full-term baby.
But Ms. Slade wouldn’t meet him until July. She was on a ventilator in a medically-induced coma for 8 weeks, and she developed a serious infection and blood clot while unconscious. It was only after a perilous 2½ months in the hospital, during which her heart stopped twice, that Ms. Slade was vaccinated against COVID-19.
“I wish I had gotten the vaccine earlier,” said Ms. Slade, 42, who remains too sick to return to work as a special education teacher in Baltimore. Doctors “kept pushing me to get vaccinated, but there just wasn’t enough information out there for me to do it.”
A year ago, there was little to no vaccine safety data for pregnant people like Ms. Slade, because they had been excluded from clinical trials run by Pfizer, Moderna, and other vaccine makers.
Lacking data, health experts were unsure and divided about how to advise expectant parents. Although U.S. health officials permitted pregnant people to be vaccinated, the World Health Organization in January 2021 actually discouraged them from doing so; it later reversed that recommendation.
The uncertainty led many women to delay vaccination, and only about two-thirds of the pregnant people who have been tracked by the Centers for Disease Control and Prevention were fully vaccinated as of Feb. 5, 2022, leaving many expectant moms at a high risk of infection and life-threatening complications.
More than 29,000 pregnant people have been hospitalized with COVID-19 and 274 have died, according to the CDC.
“There were surely women who were hospitalized because there wasn’t information available to them,” said Paul A. Offit, MD, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia.
Vaccine developers say that pregnant people – who have special health needs and risks – were excluded from clinical trials to protect them from potential side effects of novel technologies, including the Pfizer and Moderna mRNA vaccines and formulations made with cold viruses, such as the Johnson & Johnson vaccine.
But a KHN analysis also shows that pregnant people were left behind because including them in vaccine studies would have complicated and potentially delayed the delivery of COVID-19 vaccines to the broader population.
A growing number of women’s health researchers and advocates say that excluding pregnant people – and the months-long delay in recommending that they be immunized – helped fuel widespread vaccine hesitancy in this vulnerable group.
“Women and their unborn fetuses are dying of COVID infection,” said Jane Van Dis, MD, an ob.gyn. at the University of Rochester (N.Y.) Medical Center who has treated many patients like Ms. Slade. “Our failure as a society to vaccinate women in pregnancy will be remembered by the children and families who lost their mothers to this disease.”
New technology, uncertain risks
At the time COVID-19 vaccines were being developed, scientists had very little experience using mRNA vaccines in pregnant women, said Jacqueline Miller, MD, a senior vice president involved in vaccine research at Moderna.
“When you study anything in pregnant women, you have two patients, the mom and the unborn child,” Dr. Miller said. “Until we had more safety data on the platform, it wasn’t something we wanted to undertake.”
But Dr. Offit noted that vaccines have a strong record of safety in pregnancy and he sees no reason to have excluded pregnant people. None of the vaccines currently in use – including the chickenpox and rubella vaccines, which contain live viruses – have been shown to harm fetuses, he said. Doctors routinely recommend that pregnant people receive pertussis and flu vaccinations.
Dr. Offit, the coinventor of a rotavirus vaccine, said that some concerns about vaccines stem from commercial, not medical, interests. Drug makers don’t want to risk that their product will be blamed for any problems occurring in pregnant people, even if coincidental, he said.
“These companies don’t want bad news,” Dr. Offit said.
In the United States, health officials typically would have told expectant mothers not to take a vaccine that was untested during pregnancy, said Dr. Offit, a member of a committee that advises the Food and Drug Administration on vaccines.
Due to the urgency of the pandemic, health agencies instead permitted pregnant people to make up their own minds about vaccines without recommending them.
Women’s medical associations were also hampered by the lack of data. Neither the American College of Obstetricians and Gynecologists nor the Society for Maternal-Fetal Medicine actively encouraged pregnant people to be vaccinated until July 30, 2021, after the first real-world vaccine studies had been published. The CDC followed suit in August of 2021.
“If we had had this data in the beginning, we would have been able to vaccinate more women,” said Kelli Burroughs, MD, the department chair of obstetrics and gynecology at Memorial Hermann Sugar Land Hospital near Houston.
Yet anti-vaccine groups wasted no time in scaring pregnant people, flooding social media with misinformation about impaired fertility and harm to the fetus.
In the first few months after the COVID-19 vaccines were approved, some doctors were ambivalent about recommending them, and some still advise pregnant patients against vaccination.
An estimated 67% of pregnant people today are fully vaccinated, compared with about 89% of people 65 and older, another high-risk group, and 65% of Americans overall. Vaccination rates are lower among minorities, with 65% of expectant Hispanic mothers and 53% of pregnant African Americans fully vaccinated, according to the CDC.
Vaccination is especially important during pregnancy, because of increased risks of hospitalization, ICU admission, and mechanical ventilation, Dr. Burroughs said. A study released in February from the National Institutes of Health found that pregnant people with a moderate to severe COVID-19 infection also were more likely to have a C-section, deliver preterm, or develop a postpartum hemorrhage.
Black moms such as Ms. Slade were already at higher risk of maternal and infant mortality before the pandemic, because of higher underlying risks, unequal access to health care, and other factors. COVID-19 has magnified those risks, said Dr. Burroughs, who has persuaded reluctant patients by revealing that she had a healthy pregnancy and child after being vaccinated.
Ms. Slade said she has never opposed vaccines and had no hesitation about receiving other vaccines while pregnant. But she said she “just wasn’t comfortable” with COVID-19 shots.
“If there had been data out there saying the COVID shot was safe, and that nothing would happen to my baby and there was no risk of birth defects, I would have taken it,” said Ms. Slade, who has had type 2 diabetes for 12 years.
Working at warp speed
Government scientists at the NIH were concerned about the risk of COVID-19 to pregnant people from the very beginning and knew that expectant moms needed vaccines as much or more than anyone else, said Larry Corey, MD, a leader of the COVID-19 Prevention Network, which coordinated COVID-19 vaccine trials for the federal government.
But including pregnant volunteers in the larger vaccine trials could have led to interruptions and delays, Dr. Corey said. Researchers would have had to enroll thousands of pregnant volunteers to achieve statistically robust results that weren’t due to chance, he said.
Pregnancy can bring on a wide range of complications: gestational diabetes, hypertension, anemia, bleeding, blood clots, or problems with the placenta, for example. Up to 20% of people who know they’re pregnant miscarry. Because researchers would have been obliged to investigate any medical problem to make sure it wasn’t caused by one of the COVID-19 vaccines, including pregnant people might have meant having to hit pause on those trials, Dr. Corey said.
With death tolls from the pandemic mounting, “we had a mission to do this as quickly and as thoroughly as possible,” Dr. Corey said. Making COVID-19 vaccines available within a year “saved hundreds of thousands of lives.”
The first data on COVID-19 vaccine safety in pregnancy was published in April of 2021 when the CDC released an analysis of nearly 36,000 vaccinated pregnant people who had enrolled in a registry called V-safe, which allows users to log the dates of their vaccinations and any subsequent symptoms.
Later research showed that COVID-19 vaccines weren’t associated with increased risk of miscarriage or premature delivery.
Brenna Hughes, MD, a maternal-fetal medicine specialist and member of the American College of Obstetricians and Gynecologists’ COVID-19 expert group, agrees that adding pregnant people to large-scale COVID-19 vaccine and drug trials may have been impractical. But researchers could have launched parallel trials of pregnant women, once early studies showed the vaccines were safe in humans, she said.
“Would it have been hard? Everything with COVID is hard,” Dr. Hughes said. “But it would have been feasible.”
The FDA requires that researchers perform additional animal studies – called developmental and reproductive toxicity studies – before testing vaccines in pregnant people. Although these studies are essential, they take 5-6 months, and weren’t completed until late 2020, around the time the first COVID-19 vaccines were authorized for adults, said Emily Erbelding, MD, director of microbiology and infectious diseases at the National Institute of Allergy and Infectious Diseases, part of the NIH.
Pregnancy studies “were an afterthought,” said Irina Burd, MD, director of Johns Hopkins’ Integrated Research Center for Fetal Medicine and a professor of gynecology and obstetrics. “They should have been done sooner.”
The NIH is conducting a study of pregnant and postpartum people who decided on their own to be vaccinated, Dr. Erbelding said. The study is due to be completed by July 2023.
Janssen and Moderna are also conducting studies in pregnant people, both due to be completed in 2024.
Pfizer scientists encountered problems when they initiated a clinical trial, which would have randomly assigned pregnant people to receive either a vaccine or placebo. Once vaccines were widely available, many patients weren’t willing to take a chance on being unvaccinated until after delivery.
Pfizer has stopped recruiting patients and has not said whether it will publicly report any data from the trial.
Dr. Hughes said vaccine developers need to include pregnant people from the very beginning.
“There is this notion of protecting pregnant people from research,” Dr. Hughes said. “But we should be protecting patients through research, not from research.”
Recovering physically and emotionally
Ms. Slade still regrets being deprived of time with her children while she fought the disease.
Being on a ventilator kept her from spending those early weeks with her newborn, or from seeing her 9-year-old daughter, Zoe.
Even when Ms. Slade was finally able to see her son, she wasn’t able to tell him she loved him or sing a lullaby, or even talk at all, because of a breathing tube in her throat.
Today, Ms. Slade is a strong advocate of COVID-19 vaccinations, urging her friends and family to get their shots to avoid suffering the way she has.
Ms. Slade had to relearn to walk after being bedridden for weeks. Her many weeks on a ventilator may have contributed to her stomach paralysis, which often causes intense pain, nausea, and even vomiting when she eats or drinks. Ms. Slade weighs 50 pounds less today than before she became pregnant and has resorted to going to the emergency department when the pain is unbearable. “Most days, I’m just miserable,” she said.
Her family suffered as well. Like many babies born prematurely, Tristan, now nearly 9 months old and crawling, receives physical therapy to strengthen his muscles. At 15 pounds, Tristan is largely healthy, although his doctor said he has symptoms of asthma.
Ms. Slade said she would like to attend family counseling with Zoe, who rarely complains and tends to keep her feelings to herself. Ms. Slade said she knows her illness must have been terrifying for her little girl.
“The other day she was talking to me,” Ms. Slade said, “and she said, ‘You know, I almost had to bury you.’ ”
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.
Kia Slade was 7 months pregnant, unvaccinated, and fighting for breath, her oxygen levels plummeting, when her son came into the world last May.
A severe case of COVID-19 pneumonia had left Ms. Slade delirious. When the intensive care team tried to place an oxygen mask on her face, she snatched it away, she recalled. Her baby’s heart rate began to drop.
Ms. Slade’s doctor performed an emergency cesarean section at her bedside in the intensive care unit, delivering baby Tristan 10 weeks early. He weighed just 2 pounds, 14 ounces, about half the size of small full-term baby.
But Ms. Slade wouldn’t meet him until July. She was on a ventilator in a medically-induced coma for 8 weeks, and she developed a serious infection and blood clot while unconscious. It was only after a perilous 2½ months in the hospital, during which her heart stopped twice, that Ms. Slade was vaccinated against COVID-19.
“I wish I had gotten the vaccine earlier,” said Ms. Slade, 42, who remains too sick to return to work as a special education teacher in Baltimore. Doctors “kept pushing me to get vaccinated, but there just wasn’t enough information out there for me to do it.”
A year ago, there was little to no vaccine safety data for pregnant people like Ms. Slade, because they had been excluded from clinical trials run by Pfizer, Moderna, and other vaccine makers.
Lacking data, health experts were unsure and divided about how to advise expectant parents. Although U.S. health officials permitted pregnant people to be vaccinated, the World Health Organization in January 2021 actually discouraged them from doing so; it later reversed that recommendation.
The uncertainty led many women to delay vaccination, and only about two-thirds of the pregnant people who have been tracked by the Centers for Disease Control and Prevention were fully vaccinated as of Feb. 5, 2022, leaving many expectant moms at a high risk of infection and life-threatening complications.
More than 29,000 pregnant people have been hospitalized with COVID-19 and 274 have died, according to the CDC.
“There were surely women who were hospitalized because there wasn’t information available to them,” said Paul A. Offit, MD, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia.
Vaccine developers say that pregnant people – who have special health needs and risks – were excluded from clinical trials to protect them from potential side effects of novel technologies, including the Pfizer and Moderna mRNA vaccines and formulations made with cold viruses, such as the Johnson & Johnson vaccine.
But a KHN analysis also shows that pregnant people were left behind because including them in vaccine studies would have complicated and potentially delayed the delivery of COVID-19 vaccines to the broader population.
A growing number of women’s health researchers and advocates say that excluding pregnant people – and the months-long delay in recommending that they be immunized – helped fuel widespread vaccine hesitancy in this vulnerable group.
“Women and their unborn fetuses are dying of COVID infection,” said Jane Van Dis, MD, an ob.gyn. at the University of Rochester (N.Y.) Medical Center who has treated many patients like Ms. Slade. “Our failure as a society to vaccinate women in pregnancy will be remembered by the children and families who lost their mothers to this disease.”
New technology, uncertain risks
At the time COVID-19 vaccines were being developed, scientists had very little experience using mRNA vaccines in pregnant women, said Jacqueline Miller, MD, a senior vice president involved in vaccine research at Moderna.
“When you study anything in pregnant women, you have two patients, the mom and the unborn child,” Dr. Miller said. “Until we had more safety data on the platform, it wasn’t something we wanted to undertake.”
But Dr. Offit noted that vaccines have a strong record of safety in pregnancy and he sees no reason to have excluded pregnant people. None of the vaccines currently in use – including the chickenpox and rubella vaccines, which contain live viruses – have been shown to harm fetuses, he said. Doctors routinely recommend that pregnant people receive pertussis and flu vaccinations.
Dr. Offit, the coinventor of a rotavirus vaccine, said that some concerns about vaccines stem from commercial, not medical, interests. Drug makers don’t want to risk that their product will be blamed for any problems occurring in pregnant people, even if coincidental, he said.
“These companies don’t want bad news,” Dr. Offit said.
In the United States, health officials typically would have told expectant mothers not to take a vaccine that was untested during pregnancy, said Dr. Offit, a member of a committee that advises the Food and Drug Administration on vaccines.
Due to the urgency of the pandemic, health agencies instead permitted pregnant people to make up their own minds about vaccines without recommending them.
Women’s medical associations were also hampered by the lack of data. Neither the American College of Obstetricians and Gynecologists nor the Society for Maternal-Fetal Medicine actively encouraged pregnant people to be vaccinated until July 30, 2021, after the first real-world vaccine studies had been published. The CDC followed suit in August of 2021.
“If we had had this data in the beginning, we would have been able to vaccinate more women,” said Kelli Burroughs, MD, the department chair of obstetrics and gynecology at Memorial Hermann Sugar Land Hospital near Houston.
Yet anti-vaccine groups wasted no time in scaring pregnant people, flooding social media with misinformation about impaired fertility and harm to the fetus.
In the first few months after the COVID-19 vaccines were approved, some doctors were ambivalent about recommending them, and some still advise pregnant patients against vaccination.
An estimated 67% of pregnant people today are fully vaccinated, compared with about 89% of people 65 and older, another high-risk group, and 65% of Americans overall. Vaccination rates are lower among minorities, with 65% of expectant Hispanic mothers and 53% of pregnant African Americans fully vaccinated, according to the CDC.
Vaccination is especially important during pregnancy, because of increased risks of hospitalization, ICU admission, and mechanical ventilation, Dr. Burroughs said. A study released in February from the National Institutes of Health found that pregnant people with a moderate to severe COVID-19 infection also were more likely to have a C-section, deliver preterm, or develop a postpartum hemorrhage.
Black moms such as Ms. Slade were already at higher risk of maternal and infant mortality before the pandemic, because of higher underlying risks, unequal access to health care, and other factors. COVID-19 has magnified those risks, said Dr. Burroughs, who has persuaded reluctant patients by revealing that she had a healthy pregnancy and child after being vaccinated.
Ms. Slade said she has never opposed vaccines and had no hesitation about receiving other vaccines while pregnant. But she said she “just wasn’t comfortable” with COVID-19 shots.
“If there had been data out there saying the COVID shot was safe, and that nothing would happen to my baby and there was no risk of birth defects, I would have taken it,” said Ms. Slade, who has had type 2 diabetes for 12 years.
Working at warp speed
Government scientists at the NIH were concerned about the risk of COVID-19 to pregnant people from the very beginning and knew that expectant moms needed vaccines as much or more than anyone else, said Larry Corey, MD, a leader of the COVID-19 Prevention Network, which coordinated COVID-19 vaccine trials for the federal government.
But including pregnant volunteers in the larger vaccine trials could have led to interruptions and delays, Dr. Corey said. Researchers would have had to enroll thousands of pregnant volunteers to achieve statistically robust results that weren’t due to chance, he said.
Pregnancy can bring on a wide range of complications: gestational diabetes, hypertension, anemia, bleeding, blood clots, or problems with the placenta, for example. Up to 20% of people who know they’re pregnant miscarry. Because researchers would have been obliged to investigate any medical problem to make sure it wasn’t caused by one of the COVID-19 vaccines, including pregnant people might have meant having to hit pause on those trials, Dr. Corey said.
With death tolls from the pandemic mounting, “we had a mission to do this as quickly and as thoroughly as possible,” Dr. Corey said. Making COVID-19 vaccines available within a year “saved hundreds of thousands of lives.”
The first data on COVID-19 vaccine safety in pregnancy was published in April of 2021 when the CDC released an analysis of nearly 36,000 vaccinated pregnant people who had enrolled in a registry called V-safe, which allows users to log the dates of their vaccinations and any subsequent symptoms.
Later research showed that COVID-19 vaccines weren’t associated with increased risk of miscarriage or premature delivery.
Brenna Hughes, MD, a maternal-fetal medicine specialist and member of the American College of Obstetricians and Gynecologists’ COVID-19 expert group, agrees that adding pregnant people to large-scale COVID-19 vaccine and drug trials may have been impractical. But researchers could have launched parallel trials of pregnant women, once early studies showed the vaccines were safe in humans, she said.
“Would it have been hard? Everything with COVID is hard,” Dr. Hughes said. “But it would have been feasible.”
The FDA requires that researchers perform additional animal studies – called developmental and reproductive toxicity studies – before testing vaccines in pregnant people. Although these studies are essential, they take 5-6 months, and weren’t completed until late 2020, around the time the first COVID-19 vaccines were authorized for adults, said Emily Erbelding, MD, director of microbiology and infectious diseases at the National Institute of Allergy and Infectious Diseases, part of the NIH.
Pregnancy studies “were an afterthought,” said Irina Burd, MD, director of Johns Hopkins’ Integrated Research Center for Fetal Medicine and a professor of gynecology and obstetrics. “They should have been done sooner.”
The NIH is conducting a study of pregnant and postpartum people who decided on their own to be vaccinated, Dr. Erbelding said. The study is due to be completed by July 2023.
Janssen and Moderna are also conducting studies in pregnant people, both due to be completed in 2024.
Pfizer scientists encountered problems when they initiated a clinical trial, which would have randomly assigned pregnant people to receive either a vaccine or placebo. Once vaccines were widely available, many patients weren’t willing to take a chance on being unvaccinated until after delivery.
Pfizer has stopped recruiting patients and has not said whether it will publicly report any data from the trial.
Dr. Hughes said vaccine developers need to include pregnant people from the very beginning.
“There is this notion of protecting pregnant people from research,” Dr. Hughes said. “But we should be protecting patients through research, not from research.”
Recovering physically and emotionally
Ms. Slade still regrets being deprived of time with her children while she fought the disease.
Being on a ventilator kept her from spending those early weeks with her newborn, or from seeing her 9-year-old daughter, Zoe.
Even when Ms. Slade was finally able to see her son, she wasn’t able to tell him she loved him or sing a lullaby, or even talk at all, because of a breathing tube in her throat.
Today, Ms. Slade is a strong advocate of COVID-19 vaccinations, urging her friends and family to get their shots to avoid suffering the way she has.
Ms. Slade had to relearn to walk after being bedridden for weeks. Her many weeks on a ventilator may have contributed to her stomach paralysis, which often causes intense pain, nausea, and even vomiting when she eats or drinks. Ms. Slade weighs 50 pounds less today than before she became pregnant and has resorted to going to the emergency department when the pain is unbearable. “Most days, I’m just miserable,” she said.
Her family suffered as well. Like many babies born prematurely, Tristan, now nearly 9 months old and crawling, receives physical therapy to strengthen his muscles. At 15 pounds, Tristan is largely healthy, although his doctor said he has symptoms of asthma.
Ms. Slade said she would like to attend family counseling with Zoe, who rarely complains and tends to keep her feelings to herself. Ms. Slade said she knows her illness must have been terrifying for her little girl.
“The other day she was talking to me,” Ms. Slade said, “and she said, ‘You know, I almost had to bury you.’ ”
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.
Kia Slade was 7 months pregnant, unvaccinated, and fighting for breath, her oxygen levels plummeting, when her son came into the world last May.
A severe case of COVID-19 pneumonia had left Ms. Slade delirious. When the intensive care team tried to place an oxygen mask on her face, she snatched it away, she recalled. Her baby’s heart rate began to drop.
Ms. Slade’s doctor performed an emergency cesarean section at her bedside in the intensive care unit, delivering baby Tristan 10 weeks early. He weighed just 2 pounds, 14 ounces, about half the size of small full-term baby.
But Ms. Slade wouldn’t meet him until July. She was on a ventilator in a medically-induced coma for 8 weeks, and she developed a serious infection and blood clot while unconscious. It was only after a perilous 2½ months in the hospital, during which her heart stopped twice, that Ms. Slade was vaccinated against COVID-19.
“I wish I had gotten the vaccine earlier,” said Ms. Slade, 42, who remains too sick to return to work as a special education teacher in Baltimore. Doctors “kept pushing me to get vaccinated, but there just wasn’t enough information out there for me to do it.”
A year ago, there was little to no vaccine safety data for pregnant people like Ms. Slade, because they had been excluded from clinical trials run by Pfizer, Moderna, and other vaccine makers.
Lacking data, health experts were unsure and divided about how to advise expectant parents. Although U.S. health officials permitted pregnant people to be vaccinated, the World Health Organization in January 2021 actually discouraged them from doing so; it later reversed that recommendation.
The uncertainty led many women to delay vaccination, and only about two-thirds of the pregnant people who have been tracked by the Centers for Disease Control and Prevention were fully vaccinated as of Feb. 5, 2022, leaving many expectant moms at a high risk of infection and life-threatening complications.
More than 29,000 pregnant people have been hospitalized with COVID-19 and 274 have died, according to the CDC.
“There were surely women who were hospitalized because there wasn’t information available to them,” said Paul A. Offit, MD, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia.
Vaccine developers say that pregnant people – who have special health needs and risks – were excluded from clinical trials to protect them from potential side effects of novel technologies, including the Pfizer and Moderna mRNA vaccines and formulations made with cold viruses, such as the Johnson & Johnson vaccine.
But a KHN analysis also shows that pregnant people were left behind because including them in vaccine studies would have complicated and potentially delayed the delivery of COVID-19 vaccines to the broader population.
A growing number of women’s health researchers and advocates say that excluding pregnant people – and the months-long delay in recommending that they be immunized – helped fuel widespread vaccine hesitancy in this vulnerable group.
“Women and their unborn fetuses are dying of COVID infection,” said Jane Van Dis, MD, an ob.gyn. at the University of Rochester (N.Y.) Medical Center who has treated many patients like Ms. Slade. “Our failure as a society to vaccinate women in pregnancy will be remembered by the children and families who lost their mothers to this disease.”
New technology, uncertain risks
At the time COVID-19 vaccines were being developed, scientists had very little experience using mRNA vaccines in pregnant women, said Jacqueline Miller, MD, a senior vice president involved in vaccine research at Moderna.
“When you study anything in pregnant women, you have two patients, the mom and the unborn child,” Dr. Miller said. “Until we had more safety data on the platform, it wasn’t something we wanted to undertake.”
But Dr. Offit noted that vaccines have a strong record of safety in pregnancy and he sees no reason to have excluded pregnant people. None of the vaccines currently in use – including the chickenpox and rubella vaccines, which contain live viruses – have been shown to harm fetuses, he said. Doctors routinely recommend that pregnant people receive pertussis and flu vaccinations.
Dr. Offit, the coinventor of a rotavirus vaccine, said that some concerns about vaccines stem from commercial, not medical, interests. Drug makers don’t want to risk that their product will be blamed for any problems occurring in pregnant people, even if coincidental, he said.
“These companies don’t want bad news,” Dr. Offit said.
In the United States, health officials typically would have told expectant mothers not to take a vaccine that was untested during pregnancy, said Dr. Offit, a member of a committee that advises the Food and Drug Administration on vaccines.
Due to the urgency of the pandemic, health agencies instead permitted pregnant people to make up their own minds about vaccines without recommending them.
Women’s medical associations were also hampered by the lack of data. Neither the American College of Obstetricians and Gynecologists nor the Society for Maternal-Fetal Medicine actively encouraged pregnant people to be vaccinated until July 30, 2021, after the first real-world vaccine studies had been published. The CDC followed suit in August of 2021.
“If we had had this data in the beginning, we would have been able to vaccinate more women,” said Kelli Burroughs, MD, the department chair of obstetrics and gynecology at Memorial Hermann Sugar Land Hospital near Houston.
Yet anti-vaccine groups wasted no time in scaring pregnant people, flooding social media with misinformation about impaired fertility and harm to the fetus.
In the first few months after the COVID-19 vaccines were approved, some doctors were ambivalent about recommending them, and some still advise pregnant patients against vaccination.
An estimated 67% of pregnant people today are fully vaccinated, compared with about 89% of people 65 and older, another high-risk group, and 65% of Americans overall. Vaccination rates are lower among minorities, with 65% of expectant Hispanic mothers and 53% of pregnant African Americans fully vaccinated, according to the CDC.
Vaccination is especially important during pregnancy, because of increased risks of hospitalization, ICU admission, and mechanical ventilation, Dr. Burroughs said. A study released in February from the National Institutes of Health found that pregnant people with a moderate to severe COVID-19 infection also were more likely to have a C-section, deliver preterm, or develop a postpartum hemorrhage.
Black moms such as Ms. Slade were already at higher risk of maternal and infant mortality before the pandemic, because of higher underlying risks, unequal access to health care, and other factors. COVID-19 has magnified those risks, said Dr. Burroughs, who has persuaded reluctant patients by revealing that she had a healthy pregnancy and child after being vaccinated.
Ms. Slade said she has never opposed vaccines and had no hesitation about receiving other vaccines while pregnant. But she said she “just wasn’t comfortable” with COVID-19 shots.
“If there had been data out there saying the COVID shot was safe, and that nothing would happen to my baby and there was no risk of birth defects, I would have taken it,” said Ms. Slade, who has had type 2 diabetes for 12 years.
Working at warp speed
Government scientists at the NIH were concerned about the risk of COVID-19 to pregnant people from the very beginning and knew that expectant moms needed vaccines as much or more than anyone else, said Larry Corey, MD, a leader of the COVID-19 Prevention Network, which coordinated COVID-19 vaccine trials for the federal government.
But including pregnant volunteers in the larger vaccine trials could have led to interruptions and delays, Dr. Corey said. Researchers would have had to enroll thousands of pregnant volunteers to achieve statistically robust results that weren’t due to chance, he said.
Pregnancy can bring on a wide range of complications: gestational diabetes, hypertension, anemia, bleeding, blood clots, or problems with the placenta, for example. Up to 20% of people who know they’re pregnant miscarry. Because researchers would have been obliged to investigate any medical problem to make sure it wasn’t caused by one of the COVID-19 vaccines, including pregnant people might have meant having to hit pause on those trials, Dr. Corey said.
With death tolls from the pandemic mounting, “we had a mission to do this as quickly and as thoroughly as possible,” Dr. Corey said. Making COVID-19 vaccines available within a year “saved hundreds of thousands of lives.”
The first data on COVID-19 vaccine safety in pregnancy was published in April of 2021 when the CDC released an analysis of nearly 36,000 vaccinated pregnant people who had enrolled in a registry called V-safe, which allows users to log the dates of their vaccinations and any subsequent symptoms.
Later research showed that COVID-19 vaccines weren’t associated with increased risk of miscarriage or premature delivery.
Brenna Hughes, MD, a maternal-fetal medicine specialist and member of the American College of Obstetricians and Gynecologists’ COVID-19 expert group, agrees that adding pregnant people to large-scale COVID-19 vaccine and drug trials may have been impractical. But researchers could have launched parallel trials of pregnant women, once early studies showed the vaccines were safe in humans, she said.
“Would it have been hard? Everything with COVID is hard,” Dr. Hughes said. “But it would have been feasible.”
The FDA requires that researchers perform additional animal studies – called developmental and reproductive toxicity studies – before testing vaccines in pregnant people. Although these studies are essential, they take 5-6 months, and weren’t completed until late 2020, around the time the first COVID-19 vaccines were authorized for adults, said Emily Erbelding, MD, director of microbiology and infectious diseases at the National Institute of Allergy and Infectious Diseases, part of the NIH.
Pregnancy studies “were an afterthought,” said Irina Burd, MD, director of Johns Hopkins’ Integrated Research Center for Fetal Medicine and a professor of gynecology and obstetrics. “They should have been done sooner.”
The NIH is conducting a study of pregnant and postpartum people who decided on their own to be vaccinated, Dr. Erbelding said. The study is due to be completed by July 2023.
Janssen and Moderna are also conducting studies in pregnant people, both due to be completed in 2024.
Pfizer scientists encountered problems when they initiated a clinical trial, which would have randomly assigned pregnant people to receive either a vaccine or placebo. Once vaccines were widely available, many patients weren’t willing to take a chance on being unvaccinated until after delivery.
Pfizer has stopped recruiting patients and has not said whether it will publicly report any data from the trial.
Dr. Hughes said vaccine developers need to include pregnant people from the very beginning.
“There is this notion of protecting pregnant people from research,” Dr. Hughes said. “But we should be protecting patients through research, not from research.”
Recovering physically and emotionally
Ms. Slade still regrets being deprived of time with her children while she fought the disease.
Being on a ventilator kept her from spending those early weeks with her newborn, or from seeing her 9-year-old daughter, Zoe.
Even when Ms. Slade was finally able to see her son, she wasn’t able to tell him she loved him or sing a lullaby, or even talk at all, because of a breathing tube in her throat.
Today, Ms. Slade is a strong advocate of COVID-19 vaccinations, urging her friends and family to get their shots to avoid suffering the way she has.
Ms. Slade had to relearn to walk after being bedridden for weeks. Her many weeks on a ventilator may have contributed to her stomach paralysis, which often causes intense pain, nausea, and even vomiting when she eats or drinks. Ms. Slade weighs 50 pounds less today than before she became pregnant and has resorted to going to the emergency department when the pain is unbearable. “Most days, I’m just miserable,” she said.
Her family suffered as well. Like many babies born prematurely, Tristan, now nearly 9 months old and crawling, receives physical therapy to strengthen his muscles. At 15 pounds, Tristan is largely healthy, although his doctor said he has symptoms of asthma.
Ms. Slade said she would like to attend family counseling with Zoe, who rarely complains and tends to keep her feelings to herself. Ms. Slade said she knows her illness must have been terrifying for her little girl.
“The other day she was talking to me,” Ms. Slade said, “and she said, ‘You know, I almost had to bury you.’ ”
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.
First recording of dying brain shows memory, meditation patterns
Although only a single case study, researchers say the recording raises the possibility that as we die, our lives really do flash before our eyes.
“The same neurophysiological activity patterns that occur in our brains when we dream, remember, meditate, concentrate – these same patterns also appear just before we die,” study investigator Ajmal Zemmar, MD, PhD, assistant professor of neurosurgery at the University of Louisville (Ky.), said in an interview.
The research was published online Feb. 22, 2022, in the Frontiers in Aging Neuroscience.
Accidental finding
The recording of brain activity was captured inadvertently in 2016 when neuroscientists used continuous EEG to detect and treat seizures in an 87-year-old man who had developed epilepsy after a traumatic brain injury, While undergoing the EEG, the patient had a cardiac arrest and died.
In the 30 seconds before and after blood flow to the brain stopped, the EEG showed an increase in gamma oscillations. These are brain waves known to be involved in high cognitive functions, including conscious perception and memory flashbacks.
Researchers also noted changes in alpha, theta, delta, and beta wave activity just before and just after cardiac arrest, and that changes in one type modulated changes in others. That suggests a coordinated rhythm, which further suggests the activity is more than just the firing of neurons as they die.
“When you observe this and you observe the rhythmic oscillation, you are inclined to think this may be a coordinated activity pattern of the brain rather than a mere discharge when the brain dies,” Dr. Zemmar said.
Although they’ve had the data since 2016, Dr. Zemmar and colleagues held off on publishing in the hopes of finding similar recordings in other individuals. That their 5-year search yielded no results illustrates just how difficult a study like this is to conduct, Dr. Zemmar noted. “We’re trying to figure out how to do this in a predictable way, but obtaining datasets like this is going to be challenging,” he said.
Although Dr. Zemmar was unable to find recordings of activity in the dying brains of other humans, he did find a similar study conducted with rats in 2013. In that research, investigators reported a surge of brain activity in rats just prior to and immediately after experimental cardiac arrest. Changes in high- and low-frequency brain waves mirrored those documented in the current case study.
Bringing a picture together
Commenting on the new study, George Mashour, MD, PhD, professor and chair of anesthesiology and professor of neurosurgery and pharmacology at the University of Michigan, Ann Arbor, said the results are eerily similar to a 2013 study that he coauthored.
Although the current research is just a single case study, Dr. Mashour said when taken with his team’s findings in rats and other work, the new findings are “starting to put a picture together of what might be going on in the dying brain.”
“They were able to record throughout the process of cardiac arrest and death and what they found was strikingly similar to what we found in our highly controlled animal study,” said Dr. Mashour, who is also the founding director of the Center for Consciousness Science at the University of Michigan.
“There was a surge of higher-frequency activity and there was coherence across different parts of the brain,” he added. “That suggests that what we found in the rigorous controlled setting of a laboratory actually translates to humans who are undergoing the clinical process of dying.”
What remains unclear is whether this brain activity explains the near-death experiences described in the literature, which include “life recall” of memories, Dr. Mashour said. “This higher-frequency surge that’s happening around the time of death, is that correlated with experiencing something like this near-death experience? Or is it just a neural feature that can just as easily happen in an unconscious brain?”
The study was funded by the Heidi Demetriades Foundation, the ETH Zürich Foundation, and the Henan Provincial People’s Hospital Outstanding Talents Founding Grant Project. Dr. Zemmar and Dr. Mashour disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Although only a single case study, researchers say the recording raises the possibility that as we die, our lives really do flash before our eyes.
“The same neurophysiological activity patterns that occur in our brains when we dream, remember, meditate, concentrate – these same patterns also appear just before we die,” study investigator Ajmal Zemmar, MD, PhD, assistant professor of neurosurgery at the University of Louisville (Ky.), said in an interview.
The research was published online Feb. 22, 2022, in the Frontiers in Aging Neuroscience.
Accidental finding
The recording of brain activity was captured inadvertently in 2016 when neuroscientists used continuous EEG to detect and treat seizures in an 87-year-old man who had developed epilepsy after a traumatic brain injury, While undergoing the EEG, the patient had a cardiac arrest and died.
In the 30 seconds before and after blood flow to the brain stopped, the EEG showed an increase in gamma oscillations. These are brain waves known to be involved in high cognitive functions, including conscious perception and memory flashbacks.
Researchers also noted changes in alpha, theta, delta, and beta wave activity just before and just after cardiac arrest, and that changes in one type modulated changes in others. That suggests a coordinated rhythm, which further suggests the activity is more than just the firing of neurons as they die.
“When you observe this and you observe the rhythmic oscillation, you are inclined to think this may be a coordinated activity pattern of the brain rather than a mere discharge when the brain dies,” Dr. Zemmar said.
Although they’ve had the data since 2016, Dr. Zemmar and colleagues held off on publishing in the hopes of finding similar recordings in other individuals. That their 5-year search yielded no results illustrates just how difficult a study like this is to conduct, Dr. Zemmar noted. “We’re trying to figure out how to do this in a predictable way, but obtaining datasets like this is going to be challenging,” he said.
Although Dr. Zemmar was unable to find recordings of activity in the dying brains of other humans, he did find a similar study conducted with rats in 2013. In that research, investigators reported a surge of brain activity in rats just prior to and immediately after experimental cardiac arrest. Changes in high- and low-frequency brain waves mirrored those documented in the current case study.
Bringing a picture together
Commenting on the new study, George Mashour, MD, PhD, professor and chair of anesthesiology and professor of neurosurgery and pharmacology at the University of Michigan, Ann Arbor, said the results are eerily similar to a 2013 study that he coauthored.
Although the current research is just a single case study, Dr. Mashour said when taken with his team’s findings in rats and other work, the new findings are “starting to put a picture together of what might be going on in the dying brain.”
“They were able to record throughout the process of cardiac arrest and death and what they found was strikingly similar to what we found in our highly controlled animal study,” said Dr. Mashour, who is also the founding director of the Center for Consciousness Science at the University of Michigan.
“There was a surge of higher-frequency activity and there was coherence across different parts of the brain,” he added. “That suggests that what we found in the rigorous controlled setting of a laboratory actually translates to humans who are undergoing the clinical process of dying.”
What remains unclear is whether this brain activity explains the near-death experiences described in the literature, which include “life recall” of memories, Dr. Mashour said. “This higher-frequency surge that’s happening around the time of death, is that correlated with experiencing something like this near-death experience? Or is it just a neural feature that can just as easily happen in an unconscious brain?”
The study was funded by the Heidi Demetriades Foundation, the ETH Zürich Foundation, and the Henan Provincial People’s Hospital Outstanding Talents Founding Grant Project. Dr. Zemmar and Dr. Mashour disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Although only a single case study, researchers say the recording raises the possibility that as we die, our lives really do flash before our eyes.
“The same neurophysiological activity patterns that occur in our brains when we dream, remember, meditate, concentrate – these same patterns also appear just before we die,” study investigator Ajmal Zemmar, MD, PhD, assistant professor of neurosurgery at the University of Louisville (Ky.), said in an interview.
The research was published online Feb. 22, 2022, in the Frontiers in Aging Neuroscience.
Accidental finding
The recording of brain activity was captured inadvertently in 2016 when neuroscientists used continuous EEG to detect and treat seizures in an 87-year-old man who had developed epilepsy after a traumatic brain injury, While undergoing the EEG, the patient had a cardiac arrest and died.
In the 30 seconds before and after blood flow to the brain stopped, the EEG showed an increase in gamma oscillations. These are brain waves known to be involved in high cognitive functions, including conscious perception and memory flashbacks.
Researchers also noted changes in alpha, theta, delta, and beta wave activity just before and just after cardiac arrest, and that changes in one type modulated changes in others. That suggests a coordinated rhythm, which further suggests the activity is more than just the firing of neurons as they die.
“When you observe this and you observe the rhythmic oscillation, you are inclined to think this may be a coordinated activity pattern of the brain rather than a mere discharge when the brain dies,” Dr. Zemmar said.
Although they’ve had the data since 2016, Dr. Zemmar and colleagues held off on publishing in the hopes of finding similar recordings in other individuals. That their 5-year search yielded no results illustrates just how difficult a study like this is to conduct, Dr. Zemmar noted. “We’re trying to figure out how to do this in a predictable way, but obtaining datasets like this is going to be challenging,” he said.
Although Dr. Zemmar was unable to find recordings of activity in the dying brains of other humans, he did find a similar study conducted with rats in 2013. In that research, investigators reported a surge of brain activity in rats just prior to and immediately after experimental cardiac arrest. Changes in high- and low-frequency brain waves mirrored those documented in the current case study.
Bringing a picture together
Commenting on the new study, George Mashour, MD, PhD, professor and chair of anesthesiology and professor of neurosurgery and pharmacology at the University of Michigan, Ann Arbor, said the results are eerily similar to a 2013 study that he coauthored.
Although the current research is just a single case study, Dr. Mashour said when taken with his team’s findings in rats and other work, the new findings are “starting to put a picture together of what might be going on in the dying brain.”
“They were able to record throughout the process of cardiac arrest and death and what they found was strikingly similar to what we found in our highly controlled animal study,” said Dr. Mashour, who is also the founding director of the Center for Consciousness Science at the University of Michigan.
“There was a surge of higher-frequency activity and there was coherence across different parts of the brain,” he added. “That suggests that what we found in the rigorous controlled setting of a laboratory actually translates to humans who are undergoing the clinical process of dying.”
What remains unclear is whether this brain activity explains the near-death experiences described in the literature, which include “life recall” of memories, Dr. Mashour said. “This higher-frequency surge that’s happening around the time of death, is that correlated with experiencing something like this near-death experience? Or is it just a neural feature that can just as easily happen in an unconscious brain?”
The study was funded by the Heidi Demetriades Foundation, the ETH Zürich Foundation, and the Henan Provincial People’s Hospital Outstanding Talents Founding Grant Project. Dr. Zemmar and Dr. Mashour disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM FRONTIERS IN AGING NEUROSCIENCE
In-hospital detox or not, anti-CGRPs show efficacy for medication overuse headache
, according to investigators.
Abruptly discontinuing overused analgesics with health care provider oversight – a frequently resource-intensive and challenging process – is no more effective for controlling medication overuse headache than simply advising patients to stop, reported lead author Umberto Pensato, MD, of the University of Bologna, Italy, and colleagues.
“[C]urrently, the abrupt discontinuation of the overused painkiller(s), accompanied by the start of a pharmacological preventive therapy, is the most recommended strategy [for medication overuse headache],” the investigators wrote in Cephalalgia. “While painkiller(s) withdrawal could be accomplished on an outpatient basis in most cases, an in-hospital setting may be required to achieve successful discontinuation in a subgroup of patients with medication overuse headache, further weighing on individual and hospital costs. Additionally hampering this approach, the abrupt discontinuation of the overused painkiller(s) invariably results in disabling withdrawal symptoms for up to 2 weeks, including a transitory worsening of headache, the so-called ‘rebound headache.’ ”
Inpatient or outpatient: Does it matter?
According to Dr. Pensato and colleagues, early evidence suggests that previous painkiller withdrawal does not impact the efficacy of anti-CGRPs for medication overuse headache, yet relevant data remain scarce. To address this knowledge gap, they conducted a prospective, real-world study exploring the relationship between detoxification and outcomes after starting anti-CGRP therapy.
Out of 401 patients enrolled based on initiation of erenumab or galcanezumab, 111 satisfied inclusion criteria, including diagnosis of chronic migraine and medication overuse headache, at least 28 days of analgesic usage and headache days per month in the preceding 3 months, and other factors. Of these 111 patients, 83 underwent in-hospital detox, while the remaining 28 patients, who declined detox based on personal reasons or COVID-19–related bed shortage, were advised to discontinue overused medication on an outpatient basis (without oversight).
The primary endpoint was medication overuse headache responder rate after 3 months, as defined by ICHD-3 diagnostic criteria. Secondary endpoints included 6-item headache impact test (HIT-6), monthly headache days (MHD), migraine disability assessment score (MIDAS), mean pain intensity (MPI), monthly pain medication intake (MPMI), baseline predictors of response/refractoriness, and safety.
Three months after starting anti-CGRP therapy, 59% of patients had resolution of medication overuse headache, including 57% in the inpatient detox group and 64% in the outpatient group, a difference that was not statistically significant (P = .4788). Approximately half of the patients (51%) had at least 50% reduction in monthly headache days; although the rate was numerically lower in the inpatient group compared with the outpatient group, the difference was again not significant (51% vs. 54%; P = .8393).
“Our results support the emerging evidence that anti-CGRP drugs may be effective in these patients irrespective of the detoxification program,” the investigators concluded. “Further studies are needed to definitively confirm these results, potentially leading to a paradigm shift in the management of medication overuse headache.”
Abrupt or gradual detox?
According to Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, and editor-in-chief of Neurology Reviews, the study was hampered by two major design limitations.
“The biggest problem I see is that the two groups were treated very differently for their detoxification,” Dr. Rapoport said. “One group was detoxified abruptly in the hospital, so the authors were sure that the patients were off acute-care medication before they started their preventives. The other group was advised to stop their medication on an outpatient basis. The issue is that we have no follow-up as to whether the outpatients did or did not abruptly detoxify. A bigger issue was that the two groups were not randomized so there are many other variables that may have come into consideration.”
Still, Dr. Rapoport, a past president of the International Headache Society (IHS), noted that the findings strengthen a growing body of evidence supporting the efficacy of monoclonal antibodies for medication overuse headache regardless of detoxification strategy. He cited a 2020 study by Carlsen and colleagues conducted at the Danish Headache Center in Copenhagen, which reported similar medication overuse headache outcomes across three randomized cohorts whether they received preventive therapy with detoxification, preventive therapy without detoxification, or detoxification followed 2 months later by preventive therapy.
“What I have noticed since we have had monoclonal antibodies in our armamentarium is that these drugs work very well even when the patient has not fully detoxified,” Dr. Rapoport said. “What I do with my patients is not teach them how to detoxify now, but simply educate them to take fewer acute care medications as their headaches get better from the monoclonal antibodies; they should try to take fewer acute care medications for milder, shorter headaches, and just let them go away on their own. Previous research suggests that even when a patient is not educated at all about medication overuse headache and the reason for detoxification, monoclonal antibodies still work in the presence of medication overuse headache, and improve it.”
The investigators disclosed relationships with Allergan, Novartis, Teva, and others. Dr. Rapoport is on the speakers bureau for AbbVie.
, according to investigators.
Abruptly discontinuing overused analgesics with health care provider oversight – a frequently resource-intensive and challenging process – is no more effective for controlling medication overuse headache than simply advising patients to stop, reported lead author Umberto Pensato, MD, of the University of Bologna, Italy, and colleagues.
“[C]urrently, the abrupt discontinuation of the overused painkiller(s), accompanied by the start of a pharmacological preventive therapy, is the most recommended strategy [for medication overuse headache],” the investigators wrote in Cephalalgia. “While painkiller(s) withdrawal could be accomplished on an outpatient basis in most cases, an in-hospital setting may be required to achieve successful discontinuation in a subgroup of patients with medication overuse headache, further weighing on individual and hospital costs. Additionally hampering this approach, the abrupt discontinuation of the overused painkiller(s) invariably results in disabling withdrawal symptoms for up to 2 weeks, including a transitory worsening of headache, the so-called ‘rebound headache.’ ”
Inpatient or outpatient: Does it matter?
According to Dr. Pensato and colleagues, early evidence suggests that previous painkiller withdrawal does not impact the efficacy of anti-CGRPs for medication overuse headache, yet relevant data remain scarce. To address this knowledge gap, they conducted a prospective, real-world study exploring the relationship between detoxification and outcomes after starting anti-CGRP therapy.
Out of 401 patients enrolled based on initiation of erenumab or galcanezumab, 111 satisfied inclusion criteria, including diagnosis of chronic migraine and medication overuse headache, at least 28 days of analgesic usage and headache days per month in the preceding 3 months, and other factors. Of these 111 patients, 83 underwent in-hospital detox, while the remaining 28 patients, who declined detox based on personal reasons or COVID-19–related bed shortage, were advised to discontinue overused medication on an outpatient basis (without oversight).
The primary endpoint was medication overuse headache responder rate after 3 months, as defined by ICHD-3 diagnostic criteria. Secondary endpoints included 6-item headache impact test (HIT-6), monthly headache days (MHD), migraine disability assessment score (MIDAS), mean pain intensity (MPI), monthly pain medication intake (MPMI), baseline predictors of response/refractoriness, and safety.
Three months after starting anti-CGRP therapy, 59% of patients had resolution of medication overuse headache, including 57% in the inpatient detox group and 64% in the outpatient group, a difference that was not statistically significant (P = .4788). Approximately half of the patients (51%) had at least 50% reduction in monthly headache days; although the rate was numerically lower in the inpatient group compared with the outpatient group, the difference was again not significant (51% vs. 54%; P = .8393).
“Our results support the emerging evidence that anti-CGRP drugs may be effective in these patients irrespective of the detoxification program,” the investigators concluded. “Further studies are needed to definitively confirm these results, potentially leading to a paradigm shift in the management of medication overuse headache.”
Abrupt or gradual detox?
According to Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, and editor-in-chief of Neurology Reviews, the study was hampered by two major design limitations.
“The biggest problem I see is that the two groups were treated very differently for their detoxification,” Dr. Rapoport said. “One group was detoxified abruptly in the hospital, so the authors were sure that the patients were off acute-care medication before they started their preventives. The other group was advised to stop their medication on an outpatient basis. The issue is that we have no follow-up as to whether the outpatients did or did not abruptly detoxify. A bigger issue was that the two groups were not randomized so there are many other variables that may have come into consideration.”
Still, Dr. Rapoport, a past president of the International Headache Society (IHS), noted that the findings strengthen a growing body of evidence supporting the efficacy of monoclonal antibodies for medication overuse headache regardless of detoxification strategy. He cited a 2020 study by Carlsen and colleagues conducted at the Danish Headache Center in Copenhagen, which reported similar medication overuse headache outcomes across three randomized cohorts whether they received preventive therapy with detoxification, preventive therapy without detoxification, or detoxification followed 2 months later by preventive therapy.
“What I have noticed since we have had monoclonal antibodies in our armamentarium is that these drugs work very well even when the patient has not fully detoxified,” Dr. Rapoport said. “What I do with my patients is not teach them how to detoxify now, but simply educate them to take fewer acute care medications as their headaches get better from the monoclonal antibodies; they should try to take fewer acute care medications for milder, shorter headaches, and just let them go away on their own. Previous research suggests that even when a patient is not educated at all about medication overuse headache and the reason for detoxification, monoclonal antibodies still work in the presence of medication overuse headache, and improve it.”
The investigators disclosed relationships with Allergan, Novartis, Teva, and others. Dr. Rapoport is on the speakers bureau for AbbVie.
, according to investigators.
Abruptly discontinuing overused analgesics with health care provider oversight – a frequently resource-intensive and challenging process – is no more effective for controlling medication overuse headache than simply advising patients to stop, reported lead author Umberto Pensato, MD, of the University of Bologna, Italy, and colleagues.
“[C]urrently, the abrupt discontinuation of the overused painkiller(s), accompanied by the start of a pharmacological preventive therapy, is the most recommended strategy [for medication overuse headache],” the investigators wrote in Cephalalgia. “While painkiller(s) withdrawal could be accomplished on an outpatient basis in most cases, an in-hospital setting may be required to achieve successful discontinuation in a subgroup of patients with medication overuse headache, further weighing on individual and hospital costs. Additionally hampering this approach, the abrupt discontinuation of the overused painkiller(s) invariably results in disabling withdrawal symptoms for up to 2 weeks, including a transitory worsening of headache, the so-called ‘rebound headache.’ ”
Inpatient or outpatient: Does it matter?
According to Dr. Pensato and colleagues, early evidence suggests that previous painkiller withdrawal does not impact the efficacy of anti-CGRPs for medication overuse headache, yet relevant data remain scarce. To address this knowledge gap, they conducted a prospective, real-world study exploring the relationship between detoxification and outcomes after starting anti-CGRP therapy.
Out of 401 patients enrolled based on initiation of erenumab or galcanezumab, 111 satisfied inclusion criteria, including diagnosis of chronic migraine and medication overuse headache, at least 28 days of analgesic usage and headache days per month in the preceding 3 months, and other factors. Of these 111 patients, 83 underwent in-hospital detox, while the remaining 28 patients, who declined detox based on personal reasons or COVID-19–related bed shortage, were advised to discontinue overused medication on an outpatient basis (without oversight).
The primary endpoint was medication overuse headache responder rate after 3 months, as defined by ICHD-3 diagnostic criteria. Secondary endpoints included 6-item headache impact test (HIT-6), monthly headache days (MHD), migraine disability assessment score (MIDAS), mean pain intensity (MPI), monthly pain medication intake (MPMI), baseline predictors of response/refractoriness, and safety.
Three months after starting anti-CGRP therapy, 59% of patients had resolution of medication overuse headache, including 57% in the inpatient detox group and 64% in the outpatient group, a difference that was not statistically significant (P = .4788). Approximately half of the patients (51%) had at least 50% reduction in monthly headache days; although the rate was numerically lower in the inpatient group compared with the outpatient group, the difference was again not significant (51% vs. 54%; P = .8393).
“Our results support the emerging evidence that anti-CGRP drugs may be effective in these patients irrespective of the detoxification program,” the investigators concluded. “Further studies are needed to definitively confirm these results, potentially leading to a paradigm shift in the management of medication overuse headache.”
Abrupt or gradual detox?
According to Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, and editor-in-chief of Neurology Reviews, the study was hampered by two major design limitations.
“The biggest problem I see is that the two groups were treated very differently for their detoxification,” Dr. Rapoport said. “One group was detoxified abruptly in the hospital, so the authors were sure that the patients were off acute-care medication before they started their preventives. The other group was advised to stop their medication on an outpatient basis. The issue is that we have no follow-up as to whether the outpatients did or did not abruptly detoxify. A bigger issue was that the two groups were not randomized so there are many other variables that may have come into consideration.”
Still, Dr. Rapoport, a past president of the International Headache Society (IHS), noted that the findings strengthen a growing body of evidence supporting the efficacy of monoclonal antibodies for medication overuse headache regardless of detoxification strategy. He cited a 2020 study by Carlsen and colleagues conducted at the Danish Headache Center in Copenhagen, which reported similar medication overuse headache outcomes across three randomized cohorts whether they received preventive therapy with detoxification, preventive therapy without detoxification, or detoxification followed 2 months later by preventive therapy.
“What I have noticed since we have had monoclonal antibodies in our armamentarium is that these drugs work very well even when the patient has not fully detoxified,” Dr. Rapoport said. “What I do with my patients is not teach them how to detoxify now, but simply educate them to take fewer acute care medications as their headaches get better from the monoclonal antibodies; they should try to take fewer acute care medications for milder, shorter headaches, and just let them go away on their own. Previous research suggests that even when a patient is not educated at all about medication overuse headache and the reason for detoxification, monoclonal antibodies still work in the presence of medication overuse headache, and improve it.”
The investigators disclosed relationships with Allergan, Novartis, Teva, and others. Dr. Rapoport is on the speakers bureau for AbbVie.
FROM CEPHALALGIA
Global data suggest rising CLL incidence since 1990
Either way, “to our best knowledge, this study is the first study to provide a comprehensive description of the epidemiology and global burden of CLL worldwide,” the authors reported in BioMedical Engineering Online.
The findings are an evaluation of data from the 2019 Global Burden of Disease study, which includes epidemiological data on 369 diseases in 204 nations and territories around the world.
According to the analysis, the age-standardized incidence rate of CLL rose globally over the last 3 decades, from 0.76 per 100,000 persons in 1990 to 1.34 per 100,000 in 2019, for an estimated annual percentage change of 1.86%.
While increases were observed across all economic levels, the highest increases were observed in regions with the highest social determinant index. Notably, the fastest rise was observed in middle-income regions.
“What cannot be ignored is the rapid growth of the disease burden in middle [social determinant index] regions, which potentially indicated an underestimated incidence and mortality in underdeveloped countries,” write the authors, led by senior author Huafeng Wang, MD, of the department of hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.
The highest annual age-standardized incidence rates in 2019 occurred in western Europe, high-income areas of North America and central Europe, while the fastest increase in the incidence of CLL occurred in east Asia, central Europe, and Andean Latin America, according to the study.
Mortality rates
The age-standardized death rate from CLL also increased globally, from 0.40 per 100,000 persons in 1990 to 0.58 per 100,000 in 2019, for an estimated annual percentage change of 1.17.
The increases in death rates were observed across all income regions over the study period, with the highest age-standardized death rate in 2019, consistent with incidence rates, occurring in the highest-income regions, specifically in central Europe, western Europe, and high-income North America.
The geographic trends were similar in terms of disability-adjusted life-years, which increased globally from 9.20 per 100,000 persons in 1990 to 12.26 per 100,000 in 2019, for an estimated annual percentage change of 0.92%.
The authors noted that the geographic variation of CLL is consistent with research suggesting that White ancestry is a risk factor for this leukemia. And while the incidence of CLL is generally low in the 22 nations of the Arab League, the burden of disease is high in Israel.
Age and gender
The study shows that, during the past 30 years in general, CLL was more common among males, with some regional differences. For instance, in contrast to global trends, females in low-income regions accounted for the majority of incidence and mortality.
The majority of CLL cases occurred in people over the age of 50, which is consistent with known patterns of CLL occurring in older patients. Of note, the majority of cases between the ages of 50 and 69 were in low-income regions, while more than half of the incidence cases in higher-income regions were among those over the age of 70.
Risk factors
Key risk factors that may to be linked to CLL-related mortality and disability include high body mass index, occupational exposure to benzene and formaldehyde, and smoking, which was the strongest risk factor, the authors reported.
Obesity has previously been linked with an increased risk of lymphohematopoietic cancers in general and with poorer responses to treatment and reduced progression-free survival in CLL, in particular.
While the database otherwise provided only limited insights into potential CLL risk factors, “among the factors [the database] provided, the risk of benzene and formaldehyde exposure should be paid attention to,” Dr. Wang said in an interview.
“Different from other risk factors, emerging evidence has clearly pointed out the close relationship between benzene and formaldehyde exposure and hematological malignancies,” he explained. “With globalization, a large number of factories moved to less developed regions. The problem of occupational toxic exposure needs to be addressed.”
In general, the trends in the current study are consistent with previous research showing that, while there was a significant global decrease in leukemia incidence between 1990 and 2017, the incidence rates of CLL as well as acute myeloid leukemia (AML) significantly increased in most countries during that period.
“The age-standardized incidence rate of AML has steadily increased over the past 30 years, but not as rapidly as CLL,” Dr. Wang said.
He added that an encouraging sign is the “significant decline” in the age-standardized rate of chronic myeloid leukemia seen with the advent of tyrosine kinase inhibitors (TKIs).
“Perhaps for CLL, the emergence of epoch-making therapies like TKIs will also contribute to the reduction of disease burden [with that disease],” he said.
Surveillance bias?
The authors note a key caveat that the lower rates observed in low-income regions could be related to underreporting and lower screening of cancers in those regions. However, commenting on the study, Robert Peter Gale, MD, PhD, suggested that, conversely, the trends may represent a surveillance bias, reflecting an increased detection of CLL.
In fact, “it is most unlikely the incidence of CLL is really increasing,” Dr. Gale, visiting professor of hematology at the Hematology Research Centre, department of immunology and inflammation, Imperial College London, said in an interview.
“More than one-half of people with CLL have no signs or symptoms, and the diagnosis is made when they have a blood test done for unrelated reasons,” such as in the process of qualifying for life or medical insurance or for a new job, he explained. “The more testing you do, the more cases you will detect.”
Dr. Gale pointed out that research his team has conducted in China also showed an increasing incidence of CLL. However, “on closer study, we found about two-thirds of cases were incidental, namely cases detected under circumstances [such as blood testing for a job].”
Shen-Miao Yang, MD, first author of that study, agreed and noted that improved treatment with drugs such as Bruton kinase inhibitors also can have the effect of increasing incidence – by extending lives.
“More patients are diagnosed, [and] receive the new agent, and their longer survival contributes to the increased burden of CLL,” Dr. Yang of People’s Hospital of Peking University, Peking University Institute of Hematology, Beijing, said in an interview.
Furthermore, “advanced techniques such as flow cytometry and fluorescence in situ hybridization are routinely used for the diagnosis and prognosis of CLL patients – that also increases the CLL burden.”
Dr. Yang had no disclosures to report. Dr. Gale disclosed that he is a consultant to BeiGene, Fusion Pharma, La Jolla NanoMedical, MingSight Pharmaceuticals, CStone Pharmaceuticals, NexImmune, and Prolacta Bioscience; an adviser to Antengene Biotech; medical director of FFF Enterprises; a partner of AZCA; member of the board of directors of the Russian Foundation for Cancer Research Support; and on the scientific advisory board of StemRad.
Either way, “to our best knowledge, this study is the first study to provide a comprehensive description of the epidemiology and global burden of CLL worldwide,” the authors reported in BioMedical Engineering Online.
The findings are an evaluation of data from the 2019 Global Burden of Disease study, which includes epidemiological data on 369 diseases in 204 nations and territories around the world.
According to the analysis, the age-standardized incidence rate of CLL rose globally over the last 3 decades, from 0.76 per 100,000 persons in 1990 to 1.34 per 100,000 in 2019, for an estimated annual percentage change of 1.86%.
While increases were observed across all economic levels, the highest increases were observed in regions with the highest social determinant index. Notably, the fastest rise was observed in middle-income regions.
“What cannot be ignored is the rapid growth of the disease burden in middle [social determinant index] regions, which potentially indicated an underestimated incidence and mortality in underdeveloped countries,” write the authors, led by senior author Huafeng Wang, MD, of the department of hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.
The highest annual age-standardized incidence rates in 2019 occurred in western Europe, high-income areas of North America and central Europe, while the fastest increase in the incidence of CLL occurred in east Asia, central Europe, and Andean Latin America, according to the study.
Mortality rates
The age-standardized death rate from CLL also increased globally, from 0.40 per 100,000 persons in 1990 to 0.58 per 100,000 in 2019, for an estimated annual percentage change of 1.17.
The increases in death rates were observed across all income regions over the study period, with the highest age-standardized death rate in 2019, consistent with incidence rates, occurring in the highest-income regions, specifically in central Europe, western Europe, and high-income North America.
The geographic trends were similar in terms of disability-adjusted life-years, which increased globally from 9.20 per 100,000 persons in 1990 to 12.26 per 100,000 in 2019, for an estimated annual percentage change of 0.92%.
The authors noted that the geographic variation of CLL is consistent with research suggesting that White ancestry is a risk factor for this leukemia. And while the incidence of CLL is generally low in the 22 nations of the Arab League, the burden of disease is high in Israel.
Age and gender
The study shows that, during the past 30 years in general, CLL was more common among males, with some regional differences. For instance, in contrast to global trends, females in low-income regions accounted for the majority of incidence and mortality.
The majority of CLL cases occurred in people over the age of 50, which is consistent with known patterns of CLL occurring in older patients. Of note, the majority of cases between the ages of 50 and 69 were in low-income regions, while more than half of the incidence cases in higher-income regions were among those over the age of 70.
Risk factors
Key risk factors that may to be linked to CLL-related mortality and disability include high body mass index, occupational exposure to benzene and formaldehyde, and smoking, which was the strongest risk factor, the authors reported.
Obesity has previously been linked with an increased risk of lymphohematopoietic cancers in general and with poorer responses to treatment and reduced progression-free survival in CLL, in particular.
While the database otherwise provided only limited insights into potential CLL risk factors, “among the factors [the database] provided, the risk of benzene and formaldehyde exposure should be paid attention to,” Dr. Wang said in an interview.
“Different from other risk factors, emerging evidence has clearly pointed out the close relationship between benzene and formaldehyde exposure and hematological malignancies,” he explained. “With globalization, a large number of factories moved to less developed regions. The problem of occupational toxic exposure needs to be addressed.”
In general, the trends in the current study are consistent with previous research showing that, while there was a significant global decrease in leukemia incidence between 1990 and 2017, the incidence rates of CLL as well as acute myeloid leukemia (AML) significantly increased in most countries during that period.
“The age-standardized incidence rate of AML has steadily increased over the past 30 years, but not as rapidly as CLL,” Dr. Wang said.
He added that an encouraging sign is the “significant decline” in the age-standardized rate of chronic myeloid leukemia seen with the advent of tyrosine kinase inhibitors (TKIs).
“Perhaps for CLL, the emergence of epoch-making therapies like TKIs will also contribute to the reduction of disease burden [with that disease],” he said.
Surveillance bias?
The authors note a key caveat that the lower rates observed in low-income regions could be related to underreporting and lower screening of cancers in those regions. However, commenting on the study, Robert Peter Gale, MD, PhD, suggested that, conversely, the trends may represent a surveillance bias, reflecting an increased detection of CLL.
In fact, “it is most unlikely the incidence of CLL is really increasing,” Dr. Gale, visiting professor of hematology at the Hematology Research Centre, department of immunology and inflammation, Imperial College London, said in an interview.
“More than one-half of people with CLL have no signs or symptoms, and the diagnosis is made when they have a blood test done for unrelated reasons,” such as in the process of qualifying for life or medical insurance or for a new job, he explained. “The more testing you do, the more cases you will detect.”
Dr. Gale pointed out that research his team has conducted in China also showed an increasing incidence of CLL. However, “on closer study, we found about two-thirds of cases were incidental, namely cases detected under circumstances [such as blood testing for a job].”
Shen-Miao Yang, MD, first author of that study, agreed and noted that improved treatment with drugs such as Bruton kinase inhibitors also can have the effect of increasing incidence – by extending lives.
“More patients are diagnosed, [and] receive the new agent, and their longer survival contributes to the increased burden of CLL,” Dr. Yang of People’s Hospital of Peking University, Peking University Institute of Hematology, Beijing, said in an interview.
Furthermore, “advanced techniques such as flow cytometry and fluorescence in situ hybridization are routinely used for the diagnosis and prognosis of CLL patients – that also increases the CLL burden.”
Dr. Yang had no disclosures to report. Dr. Gale disclosed that he is a consultant to BeiGene, Fusion Pharma, La Jolla NanoMedical, MingSight Pharmaceuticals, CStone Pharmaceuticals, NexImmune, and Prolacta Bioscience; an adviser to Antengene Biotech; medical director of FFF Enterprises; a partner of AZCA; member of the board of directors of the Russian Foundation for Cancer Research Support; and on the scientific advisory board of StemRad.
Either way, “to our best knowledge, this study is the first study to provide a comprehensive description of the epidemiology and global burden of CLL worldwide,” the authors reported in BioMedical Engineering Online.
The findings are an evaluation of data from the 2019 Global Burden of Disease study, which includes epidemiological data on 369 diseases in 204 nations and territories around the world.
According to the analysis, the age-standardized incidence rate of CLL rose globally over the last 3 decades, from 0.76 per 100,000 persons in 1990 to 1.34 per 100,000 in 2019, for an estimated annual percentage change of 1.86%.
While increases were observed across all economic levels, the highest increases were observed in regions with the highest social determinant index. Notably, the fastest rise was observed in middle-income regions.
“What cannot be ignored is the rapid growth of the disease burden in middle [social determinant index] regions, which potentially indicated an underestimated incidence and mortality in underdeveloped countries,” write the authors, led by senior author Huafeng Wang, MD, of the department of hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.
The highest annual age-standardized incidence rates in 2019 occurred in western Europe, high-income areas of North America and central Europe, while the fastest increase in the incidence of CLL occurred in east Asia, central Europe, and Andean Latin America, according to the study.
Mortality rates
The age-standardized death rate from CLL also increased globally, from 0.40 per 100,000 persons in 1990 to 0.58 per 100,000 in 2019, for an estimated annual percentage change of 1.17.
The increases in death rates were observed across all income regions over the study period, with the highest age-standardized death rate in 2019, consistent with incidence rates, occurring in the highest-income regions, specifically in central Europe, western Europe, and high-income North America.
The geographic trends were similar in terms of disability-adjusted life-years, which increased globally from 9.20 per 100,000 persons in 1990 to 12.26 per 100,000 in 2019, for an estimated annual percentage change of 0.92%.
The authors noted that the geographic variation of CLL is consistent with research suggesting that White ancestry is a risk factor for this leukemia. And while the incidence of CLL is generally low in the 22 nations of the Arab League, the burden of disease is high in Israel.
Age and gender
The study shows that, during the past 30 years in general, CLL was more common among males, with some regional differences. For instance, in contrast to global trends, females in low-income regions accounted for the majority of incidence and mortality.
The majority of CLL cases occurred in people over the age of 50, which is consistent with known patterns of CLL occurring in older patients. Of note, the majority of cases between the ages of 50 and 69 were in low-income regions, while more than half of the incidence cases in higher-income regions were among those over the age of 70.
Risk factors
Key risk factors that may to be linked to CLL-related mortality and disability include high body mass index, occupational exposure to benzene and formaldehyde, and smoking, which was the strongest risk factor, the authors reported.
Obesity has previously been linked with an increased risk of lymphohematopoietic cancers in general and with poorer responses to treatment and reduced progression-free survival in CLL, in particular.
While the database otherwise provided only limited insights into potential CLL risk factors, “among the factors [the database] provided, the risk of benzene and formaldehyde exposure should be paid attention to,” Dr. Wang said in an interview.
“Different from other risk factors, emerging evidence has clearly pointed out the close relationship between benzene and formaldehyde exposure and hematological malignancies,” he explained. “With globalization, a large number of factories moved to less developed regions. The problem of occupational toxic exposure needs to be addressed.”
In general, the trends in the current study are consistent with previous research showing that, while there was a significant global decrease in leukemia incidence between 1990 and 2017, the incidence rates of CLL as well as acute myeloid leukemia (AML) significantly increased in most countries during that period.
“The age-standardized incidence rate of AML has steadily increased over the past 30 years, but not as rapidly as CLL,” Dr. Wang said.
He added that an encouraging sign is the “significant decline” in the age-standardized rate of chronic myeloid leukemia seen with the advent of tyrosine kinase inhibitors (TKIs).
“Perhaps for CLL, the emergence of epoch-making therapies like TKIs will also contribute to the reduction of disease burden [with that disease],” he said.
Surveillance bias?
The authors note a key caveat that the lower rates observed in low-income regions could be related to underreporting and lower screening of cancers in those regions. However, commenting on the study, Robert Peter Gale, MD, PhD, suggested that, conversely, the trends may represent a surveillance bias, reflecting an increased detection of CLL.
In fact, “it is most unlikely the incidence of CLL is really increasing,” Dr. Gale, visiting professor of hematology at the Hematology Research Centre, department of immunology and inflammation, Imperial College London, said in an interview.
“More than one-half of people with CLL have no signs or symptoms, and the diagnosis is made when they have a blood test done for unrelated reasons,” such as in the process of qualifying for life or medical insurance or for a new job, he explained. “The more testing you do, the more cases you will detect.”
Dr. Gale pointed out that research his team has conducted in China also showed an increasing incidence of CLL. However, “on closer study, we found about two-thirds of cases were incidental, namely cases detected under circumstances [such as blood testing for a job].”
Shen-Miao Yang, MD, first author of that study, agreed and noted that improved treatment with drugs such as Bruton kinase inhibitors also can have the effect of increasing incidence – by extending lives.
“More patients are diagnosed, [and] receive the new agent, and their longer survival contributes to the increased burden of CLL,” Dr. Yang of People’s Hospital of Peking University, Peking University Institute of Hematology, Beijing, said in an interview.
Furthermore, “advanced techniques such as flow cytometry and fluorescence in situ hybridization are routinely used for the diagnosis and prognosis of CLL patients – that also increases the CLL burden.”
Dr. Yang had no disclosures to report. Dr. Gale disclosed that he is a consultant to BeiGene, Fusion Pharma, La Jolla NanoMedical, MingSight Pharmaceuticals, CStone Pharmaceuticals, NexImmune, and Prolacta Bioscience; an adviser to Antengene Biotech; medical director of FFF Enterprises; a partner of AZCA; member of the board of directors of the Russian Foundation for Cancer Research Support; and on the scientific advisory board of StemRad.
FROM BIOMEDICAL ENGINEERING ONLINE
Researchers tout new CLL prognostic tool
Researchers report that they’ve confirmed the usefulness of a new tool to help physicians pinpoint prognoses for patients with chronic lymphocytic leukemia (CLL).
“Physicians may use this tool to support decisions regarding supportive care, manage the patient’s and physician’s expectations, and potentially tailor therapy,” study lead author and epidemiologist Emelie Rotbain, MD, PhD, of Rigshospitalet in Copenhagen, said in an interview.
The study appeared Jan. 10 in the journal Blood Advances.
According to Dr. Rotbain,
Researchers developed the questions based on an analysis of categories in the Cumulative Illness Rating Scale that are most linked to event-free survival (EFS) from time of treatment.
The tool looks at three organ systems – vascular, upper GI, and endocrine – and asks about conditions such as diabetes and chronic use of a proton pump inhibitor, study coauthor and hematologist/oncologist Alexey V. Danilov, MD, PhD, codirector of the Toni Stephenson Lymphoma Center at the City of Hope National Medical Center, Duarte, Calif., said in an interview. The tool then generates a score based on the variables.
For the new study, the researchers retrospectively applied the tool to 4,975 patients who appeared in the Danish National CLL Register from 2008 to 2018 (61% male, median age 70.7.). Of those, 1,513 received first-line treatment during follow-up (median = 4.39 years).
At diagnosis, nearly two-thirds (63%) of patients were considered to be low risk. None of these had endocrinological, upper gastrointestinal, or vascular disease. Another 30% were considered to be at intermediate risk. The remaining 7% were at high risk. They had high levels of endocrinological (55.6%), upper gastrointestinal (64.6%), and vascular disease (91.0%).
The high-risk patients had a median survival of 6.0 years. The intermediate-risk patients lived for a median of 8.5 years, while the low-risk patients didn’t reach a median survival level.
Fifty-six percent of high-risk patients were treated within 4 years, compared to 20%-30% of intermediate- and low-risk patients. Median event-free survival from time of treatment was 8.4, 4.4, and 2.2 years for the low-, intermediate-, and high-risk groups, respectively.
The authors cautioned that “differences in survival by type of treatment, particularly in patients treated with targeted therapies who were underrepresented in this study, could influence survival and limit the generalizability of these results.”
They added that “while prognostic factors should remain key for treatment decisions, clinical trial data from pivotal phase 3 trials with novel targeted agents versus chemoimmunotherapy should be reanalyzed with addition of CLL-CI to assess the optimal treatment for patients according to CLL-CI.”
The tool is not yet available online, Dr. Danilov said, “but that is something that we as a group could potentially work on.”
Joanna Rhodes, MD, assistant professor with Northwell Health Cancer Institute/Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, N.Y., said in an interview that the tool is easy to use and appropriate to apply at first consultation. It should be used in conjunction with the International Prognostic Index for Chronic Lymphocytic Leukemia (CLL-IPI), she said.
“We often discuss frailty as a factor in types of and timing of treatment for patients with CLL, but often this is not directly measured in clinical practice,” she said. “The CLL-CI is associated with important outcomes, particularly overall survival, which is our most important metric in oncology. Additionally, it provides important information on time to first treatment and overall survival, which are useful when we are counseling patients.”
Like the study authors, Dr. Rhodes cautioned that the CLL-CI has not been validated specifically in patients treated with targeted therapies. “It may not be applicable in this setting, particularly in the front-line setting, as these treatments were underrepresented in this cohort. Further studies in this population are needed to answer this question.”
The study is funded in part by Novo Nordisk Foundation. Several study authors report various disclosures outside the scope of this study. Dr. Rhodes has no disclosures.
Researchers report that they’ve confirmed the usefulness of a new tool to help physicians pinpoint prognoses for patients with chronic lymphocytic leukemia (CLL).
“Physicians may use this tool to support decisions regarding supportive care, manage the patient’s and physician’s expectations, and potentially tailor therapy,” study lead author and epidemiologist Emelie Rotbain, MD, PhD, of Rigshospitalet in Copenhagen, said in an interview.
The study appeared Jan. 10 in the journal Blood Advances.
According to Dr. Rotbain,
Researchers developed the questions based on an analysis of categories in the Cumulative Illness Rating Scale that are most linked to event-free survival (EFS) from time of treatment.
The tool looks at three organ systems – vascular, upper GI, and endocrine – and asks about conditions such as diabetes and chronic use of a proton pump inhibitor, study coauthor and hematologist/oncologist Alexey V. Danilov, MD, PhD, codirector of the Toni Stephenson Lymphoma Center at the City of Hope National Medical Center, Duarte, Calif., said in an interview. The tool then generates a score based on the variables.
For the new study, the researchers retrospectively applied the tool to 4,975 patients who appeared in the Danish National CLL Register from 2008 to 2018 (61% male, median age 70.7.). Of those, 1,513 received first-line treatment during follow-up (median = 4.39 years).
At diagnosis, nearly two-thirds (63%) of patients were considered to be low risk. None of these had endocrinological, upper gastrointestinal, or vascular disease. Another 30% were considered to be at intermediate risk. The remaining 7% were at high risk. They had high levels of endocrinological (55.6%), upper gastrointestinal (64.6%), and vascular disease (91.0%).
The high-risk patients had a median survival of 6.0 years. The intermediate-risk patients lived for a median of 8.5 years, while the low-risk patients didn’t reach a median survival level.
Fifty-six percent of high-risk patients were treated within 4 years, compared to 20%-30% of intermediate- and low-risk patients. Median event-free survival from time of treatment was 8.4, 4.4, and 2.2 years for the low-, intermediate-, and high-risk groups, respectively.
The authors cautioned that “differences in survival by type of treatment, particularly in patients treated with targeted therapies who were underrepresented in this study, could influence survival and limit the generalizability of these results.”
They added that “while prognostic factors should remain key for treatment decisions, clinical trial data from pivotal phase 3 trials with novel targeted agents versus chemoimmunotherapy should be reanalyzed with addition of CLL-CI to assess the optimal treatment for patients according to CLL-CI.”
The tool is not yet available online, Dr. Danilov said, “but that is something that we as a group could potentially work on.”
Joanna Rhodes, MD, assistant professor with Northwell Health Cancer Institute/Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, N.Y., said in an interview that the tool is easy to use and appropriate to apply at first consultation. It should be used in conjunction with the International Prognostic Index for Chronic Lymphocytic Leukemia (CLL-IPI), she said.
“We often discuss frailty as a factor in types of and timing of treatment for patients with CLL, but often this is not directly measured in clinical practice,” she said. “The CLL-CI is associated with important outcomes, particularly overall survival, which is our most important metric in oncology. Additionally, it provides important information on time to first treatment and overall survival, which are useful when we are counseling patients.”
Like the study authors, Dr. Rhodes cautioned that the CLL-CI has not been validated specifically in patients treated with targeted therapies. “It may not be applicable in this setting, particularly in the front-line setting, as these treatments were underrepresented in this cohort. Further studies in this population are needed to answer this question.”
The study is funded in part by Novo Nordisk Foundation. Several study authors report various disclosures outside the scope of this study. Dr. Rhodes has no disclosures.
Researchers report that they’ve confirmed the usefulness of a new tool to help physicians pinpoint prognoses for patients with chronic lymphocytic leukemia (CLL).
“Physicians may use this tool to support decisions regarding supportive care, manage the patient’s and physician’s expectations, and potentially tailor therapy,” study lead author and epidemiologist Emelie Rotbain, MD, PhD, of Rigshospitalet in Copenhagen, said in an interview.
The study appeared Jan. 10 in the journal Blood Advances.
According to Dr. Rotbain,
Researchers developed the questions based on an analysis of categories in the Cumulative Illness Rating Scale that are most linked to event-free survival (EFS) from time of treatment.
The tool looks at three organ systems – vascular, upper GI, and endocrine – and asks about conditions such as diabetes and chronic use of a proton pump inhibitor, study coauthor and hematologist/oncologist Alexey V. Danilov, MD, PhD, codirector of the Toni Stephenson Lymphoma Center at the City of Hope National Medical Center, Duarte, Calif., said in an interview. The tool then generates a score based on the variables.
For the new study, the researchers retrospectively applied the tool to 4,975 patients who appeared in the Danish National CLL Register from 2008 to 2018 (61% male, median age 70.7.). Of those, 1,513 received first-line treatment during follow-up (median = 4.39 years).
At diagnosis, nearly two-thirds (63%) of patients were considered to be low risk. None of these had endocrinological, upper gastrointestinal, or vascular disease. Another 30% were considered to be at intermediate risk. The remaining 7% were at high risk. They had high levels of endocrinological (55.6%), upper gastrointestinal (64.6%), and vascular disease (91.0%).
The high-risk patients had a median survival of 6.0 years. The intermediate-risk patients lived for a median of 8.5 years, while the low-risk patients didn’t reach a median survival level.
Fifty-six percent of high-risk patients were treated within 4 years, compared to 20%-30% of intermediate- and low-risk patients. Median event-free survival from time of treatment was 8.4, 4.4, and 2.2 years for the low-, intermediate-, and high-risk groups, respectively.
The authors cautioned that “differences in survival by type of treatment, particularly in patients treated with targeted therapies who were underrepresented in this study, could influence survival and limit the generalizability of these results.”
They added that “while prognostic factors should remain key for treatment decisions, clinical trial data from pivotal phase 3 trials with novel targeted agents versus chemoimmunotherapy should be reanalyzed with addition of CLL-CI to assess the optimal treatment for patients according to CLL-CI.”
The tool is not yet available online, Dr. Danilov said, “but that is something that we as a group could potentially work on.”
Joanna Rhodes, MD, assistant professor with Northwell Health Cancer Institute/Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, N.Y., said in an interview that the tool is easy to use and appropriate to apply at first consultation. It should be used in conjunction with the International Prognostic Index for Chronic Lymphocytic Leukemia (CLL-IPI), she said.
“We often discuss frailty as a factor in types of and timing of treatment for patients with CLL, but often this is not directly measured in clinical practice,” she said. “The CLL-CI is associated with important outcomes, particularly overall survival, which is our most important metric in oncology. Additionally, it provides important information on time to first treatment and overall survival, which are useful when we are counseling patients.”
Like the study authors, Dr. Rhodes cautioned that the CLL-CI has not been validated specifically in patients treated with targeted therapies. “It may not be applicable in this setting, particularly in the front-line setting, as these treatments were underrepresented in this cohort. Further studies in this population are needed to answer this question.”
The study is funded in part by Novo Nordisk Foundation. Several study authors report various disclosures outside the scope of this study. Dr. Rhodes has no disclosures.
FROM BLOOD ADVANCES
Most Americans unaware alcohol can cause cancer
The majority of Americans are not aware that alcohol consumption causes a variety of cancers and especially do not consider wine and beer to have a link with cancer, suggest the results from a national survey.
write lead author Andrew Seidenberg, PhD, MPH, National Cancer Institute, Rockville, Md., and colleagues.
“Increasing awareness of the alcohol-cancer link, such as through multimedia campaigns and patient-provider communication, may be an important new strategy for health advocates working to implement preventive alcohol policies,” they add.
The findings were published in the February issue of the American Journal of Preventive Medicine.
“This is the first study to examine the relationship between alcohol control policy support and awareness of the alcohol-cancer link among a national U.S. sample,” the authors write.
The results show that there is some public support for the idea of adding written warnings about the alcohol-cancer risk to alcoholic beverages, which is something that a number of cancer organizations have been petitioning for.
A petition filed by the American Society of Clinical Oncology, the American Institute for Cancer Research, and Breast Cancer Prevention Partners, all in collaboration with several public health organizations, proposes labeling that would read: “WARNING: According to the Surgeon General, consumption of alcoholic beverages can cause cancer, including breast and colon cancers.”
Such labeling has “the potential to save lives by ensuring that consumers have a more accurate understanding of the link between alcohol and cancer, which will empower them to better protect their health,” the groups said in the petition.
Public support
The findings come from an analysis of the 2020 Health Information National Trends Survey 5 Cycle 4. A total of 3,865 adults participated in the survey, approximately half of whom were nondrinkers.
As well as investigating how aware people were of the alcohol-cancer link, the investigators looked at how prevalent public support might be for the following three communication-focused alcohol policies:
- Banning outdoor alcohol-related advertising
- Requiring health warnings on alcohol beverage containers
- Requiring recommended drinking guidelines on alcoholic beverage containers
“Awareness of the alcohol-cancer link was measured separately for wine, beer, and liquor by asking: In your opinion, how much does drinking the following types of alcohol affect the risk of getting cancer?” the authors explain.
“Awareness of the alcohol-cancer link was low,” the investigators comment; only about one-third (31.8%) of participants were aware that alcohol increases the risk of cancer. The figures were even lower for individual beverage type, at 20.3% for wine, 24.9% for beer, and 31.2% for liquor. Furthermore, approximately half of participants responded with “don’t know” to the three awareness items, investigators noted.
On the other hand, more than half of the Americans surveyed supported adding both health warning labels (65.1%) and information on recommended drinking guidelines (63.9%) to alcoholic beverage containers. Support was lower (34.4% of respondents) for banning outdoor alcohol advertising.
Among Americans who were aware that alcohol increased cancer risk, support was also higher for all three policies.
For example, about 75% of respondents who were aware that alcohol increases cancer risk supported adding health warnings and drinking guidelines to beverage containers, compared with about half of Americans who felt that alcohol consumption had either no effect on or decreased cancer risk.
Even among those who were aware of the alcohol-cancer link, public support for outdoor advertising was not high (37.8%), but it was even lower (23.6%) among respondents who felt alcohol had no effect on or decreased the risk of cancer.
“Policy support was highest among nondrinkers, followed by drinkers, and was lowest among heavier drinkers,” the authors report.
For example, almost 43% of nondrinkers supported restrictions on outdoor alcohol advertising, compared with only about 28.6% of drinkers and 22% of heavier drinkers. More respondents supported adding health warning labels on alcoholic beverages – 70% of nondrinkers, 65% of drinkers, and 57% of heavier drinkers, investigators observe.
The study had no specific funding. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The majority of Americans are not aware that alcohol consumption causes a variety of cancers and especially do not consider wine and beer to have a link with cancer, suggest the results from a national survey.
write lead author Andrew Seidenberg, PhD, MPH, National Cancer Institute, Rockville, Md., and colleagues.
“Increasing awareness of the alcohol-cancer link, such as through multimedia campaigns and patient-provider communication, may be an important new strategy for health advocates working to implement preventive alcohol policies,” they add.
The findings were published in the February issue of the American Journal of Preventive Medicine.
“This is the first study to examine the relationship between alcohol control policy support and awareness of the alcohol-cancer link among a national U.S. sample,” the authors write.
The results show that there is some public support for the idea of adding written warnings about the alcohol-cancer risk to alcoholic beverages, which is something that a number of cancer organizations have been petitioning for.
A petition filed by the American Society of Clinical Oncology, the American Institute for Cancer Research, and Breast Cancer Prevention Partners, all in collaboration with several public health organizations, proposes labeling that would read: “WARNING: According to the Surgeon General, consumption of alcoholic beverages can cause cancer, including breast and colon cancers.”
Such labeling has “the potential to save lives by ensuring that consumers have a more accurate understanding of the link between alcohol and cancer, which will empower them to better protect their health,” the groups said in the petition.
Public support
The findings come from an analysis of the 2020 Health Information National Trends Survey 5 Cycle 4. A total of 3,865 adults participated in the survey, approximately half of whom were nondrinkers.
As well as investigating how aware people were of the alcohol-cancer link, the investigators looked at how prevalent public support might be for the following three communication-focused alcohol policies:
- Banning outdoor alcohol-related advertising
- Requiring health warnings on alcohol beverage containers
- Requiring recommended drinking guidelines on alcoholic beverage containers
“Awareness of the alcohol-cancer link was measured separately for wine, beer, and liquor by asking: In your opinion, how much does drinking the following types of alcohol affect the risk of getting cancer?” the authors explain.
“Awareness of the alcohol-cancer link was low,” the investigators comment; only about one-third (31.8%) of participants were aware that alcohol increases the risk of cancer. The figures were even lower for individual beverage type, at 20.3% for wine, 24.9% for beer, and 31.2% for liquor. Furthermore, approximately half of participants responded with “don’t know” to the three awareness items, investigators noted.
On the other hand, more than half of the Americans surveyed supported adding both health warning labels (65.1%) and information on recommended drinking guidelines (63.9%) to alcoholic beverage containers. Support was lower (34.4% of respondents) for banning outdoor alcohol advertising.
Among Americans who were aware that alcohol increased cancer risk, support was also higher for all three policies.
For example, about 75% of respondents who were aware that alcohol increases cancer risk supported adding health warnings and drinking guidelines to beverage containers, compared with about half of Americans who felt that alcohol consumption had either no effect on or decreased cancer risk.
Even among those who were aware of the alcohol-cancer link, public support for outdoor advertising was not high (37.8%), but it was even lower (23.6%) among respondents who felt alcohol had no effect on or decreased the risk of cancer.
“Policy support was highest among nondrinkers, followed by drinkers, and was lowest among heavier drinkers,” the authors report.
For example, almost 43% of nondrinkers supported restrictions on outdoor alcohol advertising, compared with only about 28.6% of drinkers and 22% of heavier drinkers. More respondents supported adding health warning labels on alcoholic beverages – 70% of nondrinkers, 65% of drinkers, and 57% of heavier drinkers, investigators observe.
The study had no specific funding. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The majority of Americans are not aware that alcohol consumption causes a variety of cancers and especially do not consider wine and beer to have a link with cancer, suggest the results from a national survey.
write lead author Andrew Seidenberg, PhD, MPH, National Cancer Institute, Rockville, Md., and colleagues.
“Increasing awareness of the alcohol-cancer link, such as through multimedia campaigns and patient-provider communication, may be an important new strategy for health advocates working to implement preventive alcohol policies,” they add.
The findings were published in the February issue of the American Journal of Preventive Medicine.
“This is the first study to examine the relationship between alcohol control policy support and awareness of the alcohol-cancer link among a national U.S. sample,” the authors write.
The results show that there is some public support for the idea of adding written warnings about the alcohol-cancer risk to alcoholic beverages, which is something that a number of cancer organizations have been petitioning for.
A petition filed by the American Society of Clinical Oncology, the American Institute for Cancer Research, and Breast Cancer Prevention Partners, all in collaboration with several public health organizations, proposes labeling that would read: “WARNING: According to the Surgeon General, consumption of alcoholic beverages can cause cancer, including breast and colon cancers.”
Such labeling has “the potential to save lives by ensuring that consumers have a more accurate understanding of the link between alcohol and cancer, which will empower them to better protect their health,” the groups said in the petition.
Public support
The findings come from an analysis of the 2020 Health Information National Trends Survey 5 Cycle 4. A total of 3,865 adults participated in the survey, approximately half of whom were nondrinkers.
As well as investigating how aware people were of the alcohol-cancer link, the investigators looked at how prevalent public support might be for the following three communication-focused alcohol policies:
- Banning outdoor alcohol-related advertising
- Requiring health warnings on alcohol beverage containers
- Requiring recommended drinking guidelines on alcoholic beverage containers
“Awareness of the alcohol-cancer link was measured separately for wine, beer, and liquor by asking: In your opinion, how much does drinking the following types of alcohol affect the risk of getting cancer?” the authors explain.
“Awareness of the alcohol-cancer link was low,” the investigators comment; only about one-third (31.8%) of participants were aware that alcohol increases the risk of cancer. The figures were even lower for individual beverage type, at 20.3% for wine, 24.9% for beer, and 31.2% for liquor. Furthermore, approximately half of participants responded with “don’t know” to the three awareness items, investigators noted.
On the other hand, more than half of the Americans surveyed supported adding both health warning labels (65.1%) and information on recommended drinking guidelines (63.9%) to alcoholic beverage containers. Support was lower (34.4% of respondents) for banning outdoor alcohol advertising.
Among Americans who were aware that alcohol increased cancer risk, support was also higher for all three policies.
For example, about 75% of respondents who were aware that alcohol increases cancer risk supported adding health warnings and drinking guidelines to beverage containers, compared with about half of Americans who felt that alcohol consumption had either no effect on or decreased cancer risk.
Even among those who were aware of the alcohol-cancer link, public support for outdoor advertising was not high (37.8%), but it was even lower (23.6%) among respondents who felt alcohol had no effect on or decreased the risk of cancer.
“Policy support was highest among nondrinkers, followed by drinkers, and was lowest among heavier drinkers,” the authors report.
For example, almost 43% of nondrinkers supported restrictions on outdoor alcohol advertising, compared with only about 28.6% of drinkers and 22% of heavier drinkers. More respondents supported adding health warning labels on alcoholic beverages – 70% of nondrinkers, 65% of drinkers, and 57% of heavier drinkers, investigators observe.
The study had no specific funding. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE AMERICAN JOURNAL OF PREVENTIVE MEDICINE
Women at higher risk of serious adverse events from cancer therapy
and this is seen with chemotherapy, targeted agents, and especially with immunotherapy.
The finding comes from a review of more than 23,000 participants across 202 trials of various cancers (excluding sex-related cancers) that has been conducted over the past 40 years.
The investigators found a 34% increased risk of severe AEs among women, compared with men, climbing to a 49% higher risk with immunotherapy.
Women had a substantially greater risk of severe symptomatic AEs, including with immune checkpoint inhibitors and targeted tyrosine kinase inhibitors, and were more likely to experience severe hematologic AEs with chemotherapy and immunotherapy.
The particularly large sex differences with immunotherapy suggest “that studying AEs from these agents is a priority,” the investigators comment.
The article was published online on Feb. 4 in the Journal of Clinical Oncology.
“It has been understood that women have more toxicity from chemotherapy than men, but almost no research has aimed to understand whether that pattern held for novel treatments like immunotherapy or targeted therapies. We found similar large differences, especially for immune treatments,” said lead investigator Joseph Unger, PhD, a biostatistician and health services researcher at the Fred Hutchinson Cancer Research Center, Seattle, in an institutional press release.
A “better understanding of the nature of the underlying mechanisms could potentially lead to interventions or delivery modifications to reduce toxicity in women,” the investigators comment in their article.
Among a sea of possible explanations for the finding, there could be differences in how men and women metabolize cancer therapies or differences in how they perceive symptoms. Women may also receive relatively higher doses because of their body size or have higher adherence to treatment.
Whatever the case, as cancer treatment becomes increasingly individualized, “sex may be an important consideration,” Dr. Unger said.
Study details
The study involved 8,838 women and 14,458 men across the trials, which were phase 2 or 3 investigations conducted by the SWOG Cancer Research Network from 1980 to 2019. Trials including sex-related cancers were excluded. In the trials included in the review, the most common cancers were gastrointestinal and lung, followed by leukemia.
Seventy-five percent of the subjects received chemotherapy, and the rest received either targeted therapy or immunotherapy.
Two-thirds of the subjects had at least one grade 3 or higher AE; women had a 25% higher risk than men of having AEs of grade 5 or higher.
After adjusting for age, race, disease prognosis, and other factors, women were at increased risk of severe symptomatic AEs, such as nausea and pain, across all treatment lines and especially with immunotherapy, for which reports of symptomatic AEs were 66% higher.
Women also had a higher risk of symptomatic gastrointestinal AEs with all three treatments and a higher risk of sleep-related AEs with chemotherapy and immunotherapy, which “could be a function of hormonal effects interacting with cancer treatment,” the investigators said.
As for readily measurable AEs, women were at higher risk than men for objective hematologic AEs with chemotherapy, immunotherapy, and targeted therapy. There were no statistically significant sex differences in the risk of nonhematologic objective AEs.
The team notes that increased toxicity among women has been associated with improved survival, which may give AEs more time to develop. Higher rates of AEs might also signal increased delivery or efficacy of cancer treatments.
However, a previous study found that men may have a better response to immunotherapy than women. Immune checkpoint inhibitors were twice as effective as standard cancer therapies in the treatment of men with advanced solid tumors compared to their female counterparts, concluded a team that carried out a meta-analysis of 20 randomized controlled trials involving more than 11,351 patients.
The study was funded by the National Cancer Institute and others. Dr. Unger has disclosed no relevant financial relationships. Several coauthors have reported ties to a handful of companies, including Johnson & Johnson and Seattle Genetics. One is an employee of AIM Specialty Health.
A version of this article first appeared on Medscape.com.
and this is seen with chemotherapy, targeted agents, and especially with immunotherapy.
The finding comes from a review of more than 23,000 participants across 202 trials of various cancers (excluding sex-related cancers) that has been conducted over the past 40 years.
The investigators found a 34% increased risk of severe AEs among women, compared with men, climbing to a 49% higher risk with immunotherapy.
Women had a substantially greater risk of severe symptomatic AEs, including with immune checkpoint inhibitors and targeted tyrosine kinase inhibitors, and were more likely to experience severe hematologic AEs with chemotherapy and immunotherapy.
The particularly large sex differences with immunotherapy suggest “that studying AEs from these agents is a priority,” the investigators comment.
The article was published online on Feb. 4 in the Journal of Clinical Oncology.
“It has been understood that women have more toxicity from chemotherapy than men, but almost no research has aimed to understand whether that pattern held for novel treatments like immunotherapy or targeted therapies. We found similar large differences, especially for immune treatments,” said lead investigator Joseph Unger, PhD, a biostatistician and health services researcher at the Fred Hutchinson Cancer Research Center, Seattle, in an institutional press release.
A “better understanding of the nature of the underlying mechanisms could potentially lead to interventions or delivery modifications to reduce toxicity in women,” the investigators comment in their article.
Among a sea of possible explanations for the finding, there could be differences in how men and women metabolize cancer therapies or differences in how they perceive symptoms. Women may also receive relatively higher doses because of their body size or have higher adherence to treatment.
Whatever the case, as cancer treatment becomes increasingly individualized, “sex may be an important consideration,” Dr. Unger said.
Study details
The study involved 8,838 women and 14,458 men across the trials, which were phase 2 or 3 investigations conducted by the SWOG Cancer Research Network from 1980 to 2019. Trials including sex-related cancers were excluded. In the trials included in the review, the most common cancers were gastrointestinal and lung, followed by leukemia.
Seventy-five percent of the subjects received chemotherapy, and the rest received either targeted therapy or immunotherapy.
Two-thirds of the subjects had at least one grade 3 or higher AE; women had a 25% higher risk than men of having AEs of grade 5 or higher.
After adjusting for age, race, disease prognosis, and other factors, women were at increased risk of severe symptomatic AEs, such as nausea and pain, across all treatment lines and especially with immunotherapy, for which reports of symptomatic AEs were 66% higher.
Women also had a higher risk of symptomatic gastrointestinal AEs with all three treatments and a higher risk of sleep-related AEs with chemotherapy and immunotherapy, which “could be a function of hormonal effects interacting with cancer treatment,” the investigators said.
As for readily measurable AEs, women were at higher risk than men for objective hematologic AEs with chemotherapy, immunotherapy, and targeted therapy. There were no statistically significant sex differences in the risk of nonhematologic objective AEs.
The team notes that increased toxicity among women has been associated with improved survival, which may give AEs more time to develop. Higher rates of AEs might also signal increased delivery or efficacy of cancer treatments.
However, a previous study found that men may have a better response to immunotherapy than women. Immune checkpoint inhibitors were twice as effective as standard cancer therapies in the treatment of men with advanced solid tumors compared to their female counterparts, concluded a team that carried out a meta-analysis of 20 randomized controlled trials involving more than 11,351 patients.
The study was funded by the National Cancer Institute and others. Dr. Unger has disclosed no relevant financial relationships. Several coauthors have reported ties to a handful of companies, including Johnson & Johnson and Seattle Genetics. One is an employee of AIM Specialty Health.
A version of this article first appeared on Medscape.com.
and this is seen with chemotherapy, targeted agents, and especially with immunotherapy.
The finding comes from a review of more than 23,000 participants across 202 trials of various cancers (excluding sex-related cancers) that has been conducted over the past 40 years.
The investigators found a 34% increased risk of severe AEs among women, compared with men, climbing to a 49% higher risk with immunotherapy.
Women had a substantially greater risk of severe symptomatic AEs, including with immune checkpoint inhibitors and targeted tyrosine kinase inhibitors, and were more likely to experience severe hematologic AEs with chemotherapy and immunotherapy.
The particularly large sex differences with immunotherapy suggest “that studying AEs from these agents is a priority,” the investigators comment.
The article was published online on Feb. 4 in the Journal of Clinical Oncology.
“It has been understood that women have more toxicity from chemotherapy than men, but almost no research has aimed to understand whether that pattern held for novel treatments like immunotherapy or targeted therapies. We found similar large differences, especially for immune treatments,” said lead investigator Joseph Unger, PhD, a biostatistician and health services researcher at the Fred Hutchinson Cancer Research Center, Seattle, in an institutional press release.
A “better understanding of the nature of the underlying mechanisms could potentially lead to interventions or delivery modifications to reduce toxicity in women,” the investigators comment in their article.
Among a sea of possible explanations for the finding, there could be differences in how men and women metabolize cancer therapies or differences in how they perceive symptoms. Women may also receive relatively higher doses because of their body size or have higher adherence to treatment.
Whatever the case, as cancer treatment becomes increasingly individualized, “sex may be an important consideration,” Dr. Unger said.
Study details
The study involved 8,838 women and 14,458 men across the trials, which were phase 2 or 3 investigations conducted by the SWOG Cancer Research Network from 1980 to 2019. Trials including sex-related cancers were excluded. In the trials included in the review, the most common cancers were gastrointestinal and lung, followed by leukemia.
Seventy-five percent of the subjects received chemotherapy, and the rest received either targeted therapy or immunotherapy.
Two-thirds of the subjects had at least one grade 3 or higher AE; women had a 25% higher risk than men of having AEs of grade 5 or higher.
After adjusting for age, race, disease prognosis, and other factors, women were at increased risk of severe symptomatic AEs, such as nausea and pain, across all treatment lines and especially with immunotherapy, for which reports of symptomatic AEs were 66% higher.
Women also had a higher risk of symptomatic gastrointestinal AEs with all three treatments and a higher risk of sleep-related AEs with chemotherapy and immunotherapy, which “could be a function of hormonal effects interacting with cancer treatment,” the investigators said.
As for readily measurable AEs, women were at higher risk than men for objective hematologic AEs with chemotherapy, immunotherapy, and targeted therapy. There were no statistically significant sex differences in the risk of nonhematologic objective AEs.
The team notes that increased toxicity among women has been associated with improved survival, which may give AEs more time to develop. Higher rates of AEs might also signal increased delivery or efficacy of cancer treatments.
However, a previous study found that men may have a better response to immunotherapy than women. Immune checkpoint inhibitors were twice as effective as standard cancer therapies in the treatment of men with advanced solid tumors compared to their female counterparts, concluded a team that carried out a meta-analysis of 20 randomized controlled trials involving more than 11,351 patients.
The study was funded by the National Cancer Institute and others. Dr. Unger has disclosed no relevant financial relationships. Several coauthors have reported ties to a handful of companies, including Johnson & Johnson and Seattle Genetics. One is an employee of AIM Specialty Health.
A version of this article first appeared on Medscape.com.
Brain tumors exact higher mortality toll in men than women
And, researchers say, it’s not exactly clear why.
Differences in treatment may mediate some of the association, but biologic sex itself appears to be a stronger risk factor for death, according to the study published online Feb. 8 in Cancer.
The excess in male deaths is “concerning, and we need more clinical data and more biological tumor data within each histologic type of brain tumor to understand why these young adult men who would be otherwise healthy are dying of these brain tumors,” study author Lindsay Williams, PhD, MPH, with the division of epidemiology and clinical research, University of Minnesota, Minneapolis, told this news organization.
Central nervous system tumors rank among the top five cancers diagnosed in young adults aged 20-39 years.
Dr. Williams and her colleagues previously showed that men are more likely to develop brain tumors. Their latest study shows that men die more frequently from brain tumors as well.
Using the National Cancer Database, they identified 47,560 young adults aged 20-39 (47% male) diagnosed with a CNS tumor between 2004 and 2016.
After adjusting for relevant factors, males had a 47% increased risk of dying after a brain tumor diagnosis compared with females (hazard ratio, 1.47; 95% confidence interval, 1.41-1.53).
Males had significantly worse overall survival than females for all CNS tumors combined and for nine of 16 histologic types – namely, diffuse astrocytoma (HR, 1.30), anaplastic astrocytoma (HR, 1.25), glioblastoma (HR, 1.14), oligodendroglioma (HR, 1.37), oligoastrocytic tumors (HR, 1.22), ependymal tumors (HR, 1.29), other malignant gliomas (HR, 1.43), neuronal and mixed neuronal-glial tumors (HR, 1.52), and meningioma (HR, 2.01; all P < .05).
The researchers identified no histologies where females had worse survival.
Five-year survival differed between females and males by at least 5% for all histologies combined (83.2% female and 71.2% male) as well as for diffuse astrocytoma (75.1% vs. 68.5%), anaplastic astrocytoma (63.5% vs. 57.5%), oligoastrocytic tumors (80.2% vs. 74.7%), other malignant gliomas (74.1% vs. 64.9%), and germ cell tumors (92.4% vs. 86.5%).
The researchers estimated that had survival in men been equal to that of women over the study period, 20% of total deaths and 34% of male deaths could have been avoided.
They say future population-based studies are needed to confirm these findings and determine whether tumor biology or responses to therapy are driving forces of the observed male excess in death from brain tumors.
“We cannot discount the role of sex differences in diagnosis, treatment, or behavioral risk factors that may underlie the better survival for women after a brain tumor diagnosis,” they write.
“Hopefully, our research will increase awareness of sex differences in brain tumor outcomes in young adults and encourage other researchers with similar datasets to look at this same question and see if they observe a similar trend,” Dr. Williams said in an interview.
The study was supported by the National Cancer Institute. Dr. Williams has no relevant disclosures. One author, Christopher L. Moertel, MD, is chief medical officer for OX2 Therapeutics, has stock in OX2 Therapeutics, and reports patents relevant to his relationship with OX2 Therapeutics.
A version of this article first appeared on Medscape.com.
And, researchers say, it’s not exactly clear why.
Differences in treatment may mediate some of the association, but biologic sex itself appears to be a stronger risk factor for death, according to the study published online Feb. 8 in Cancer.
The excess in male deaths is “concerning, and we need more clinical data and more biological tumor data within each histologic type of brain tumor to understand why these young adult men who would be otherwise healthy are dying of these brain tumors,” study author Lindsay Williams, PhD, MPH, with the division of epidemiology and clinical research, University of Minnesota, Minneapolis, told this news organization.
Central nervous system tumors rank among the top five cancers diagnosed in young adults aged 20-39 years.
Dr. Williams and her colleagues previously showed that men are more likely to develop brain tumors. Their latest study shows that men die more frequently from brain tumors as well.
Using the National Cancer Database, they identified 47,560 young adults aged 20-39 (47% male) diagnosed with a CNS tumor between 2004 and 2016.
After adjusting for relevant factors, males had a 47% increased risk of dying after a brain tumor diagnosis compared with females (hazard ratio, 1.47; 95% confidence interval, 1.41-1.53).
Males had significantly worse overall survival than females for all CNS tumors combined and for nine of 16 histologic types – namely, diffuse astrocytoma (HR, 1.30), anaplastic astrocytoma (HR, 1.25), glioblastoma (HR, 1.14), oligodendroglioma (HR, 1.37), oligoastrocytic tumors (HR, 1.22), ependymal tumors (HR, 1.29), other malignant gliomas (HR, 1.43), neuronal and mixed neuronal-glial tumors (HR, 1.52), and meningioma (HR, 2.01; all P < .05).
The researchers identified no histologies where females had worse survival.
Five-year survival differed between females and males by at least 5% for all histologies combined (83.2% female and 71.2% male) as well as for diffuse astrocytoma (75.1% vs. 68.5%), anaplastic astrocytoma (63.5% vs. 57.5%), oligoastrocytic tumors (80.2% vs. 74.7%), other malignant gliomas (74.1% vs. 64.9%), and germ cell tumors (92.4% vs. 86.5%).
The researchers estimated that had survival in men been equal to that of women over the study period, 20% of total deaths and 34% of male deaths could have been avoided.
They say future population-based studies are needed to confirm these findings and determine whether tumor biology or responses to therapy are driving forces of the observed male excess in death from brain tumors.
“We cannot discount the role of sex differences in diagnosis, treatment, or behavioral risk factors that may underlie the better survival for women after a brain tumor diagnosis,” they write.
“Hopefully, our research will increase awareness of sex differences in brain tumor outcomes in young adults and encourage other researchers with similar datasets to look at this same question and see if they observe a similar trend,” Dr. Williams said in an interview.
The study was supported by the National Cancer Institute. Dr. Williams has no relevant disclosures. One author, Christopher L. Moertel, MD, is chief medical officer for OX2 Therapeutics, has stock in OX2 Therapeutics, and reports patents relevant to his relationship with OX2 Therapeutics.
A version of this article first appeared on Medscape.com.
And, researchers say, it’s not exactly clear why.
Differences in treatment may mediate some of the association, but biologic sex itself appears to be a stronger risk factor for death, according to the study published online Feb. 8 in Cancer.
The excess in male deaths is “concerning, and we need more clinical data and more biological tumor data within each histologic type of brain tumor to understand why these young adult men who would be otherwise healthy are dying of these brain tumors,” study author Lindsay Williams, PhD, MPH, with the division of epidemiology and clinical research, University of Minnesota, Minneapolis, told this news organization.
Central nervous system tumors rank among the top five cancers diagnosed in young adults aged 20-39 years.
Dr. Williams and her colleagues previously showed that men are more likely to develop brain tumors. Their latest study shows that men die more frequently from brain tumors as well.
Using the National Cancer Database, they identified 47,560 young adults aged 20-39 (47% male) diagnosed with a CNS tumor between 2004 and 2016.
After adjusting for relevant factors, males had a 47% increased risk of dying after a brain tumor diagnosis compared with females (hazard ratio, 1.47; 95% confidence interval, 1.41-1.53).
Males had significantly worse overall survival than females for all CNS tumors combined and for nine of 16 histologic types – namely, diffuse astrocytoma (HR, 1.30), anaplastic astrocytoma (HR, 1.25), glioblastoma (HR, 1.14), oligodendroglioma (HR, 1.37), oligoastrocytic tumors (HR, 1.22), ependymal tumors (HR, 1.29), other malignant gliomas (HR, 1.43), neuronal and mixed neuronal-glial tumors (HR, 1.52), and meningioma (HR, 2.01; all P < .05).
The researchers identified no histologies where females had worse survival.
Five-year survival differed between females and males by at least 5% for all histologies combined (83.2% female and 71.2% male) as well as for diffuse astrocytoma (75.1% vs. 68.5%), anaplastic astrocytoma (63.5% vs. 57.5%), oligoastrocytic tumors (80.2% vs. 74.7%), other malignant gliomas (74.1% vs. 64.9%), and germ cell tumors (92.4% vs. 86.5%).
The researchers estimated that had survival in men been equal to that of women over the study period, 20% of total deaths and 34% of male deaths could have been avoided.
They say future population-based studies are needed to confirm these findings and determine whether tumor biology or responses to therapy are driving forces of the observed male excess in death from brain tumors.
“We cannot discount the role of sex differences in diagnosis, treatment, or behavioral risk factors that may underlie the better survival for women after a brain tumor diagnosis,” they write.
“Hopefully, our research will increase awareness of sex differences in brain tumor outcomes in young adults and encourage other researchers with similar datasets to look at this same question and see if they observe a similar trend,” Dr. Williams said in an interview.
The study was supported by the National Cancer Institute. Dr. Williams has no relevant disclosures. One author, Christopher L. Moertel, MD, is chief medical officer for OX2 Therapeutics, has stock in OX2 Therapeutics, and reports patents relevant to his relationship with OX2 Therapeutics.
A version of this article first appeared on Medscape.com.
FROM CANCER