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Hospital-acquired pneumonia is killing patients, yet there is a simple way to stop it
Four years ago, when Dr. Karen Giuliano went to a Boston hospital for hip replacement surgery, she was given a pale-pink bucket of toiletries issued to patients in many hospitals. Inside were tissues, bar soap, deodorant, toothpaste, and, without a doubt, the worst toothbrush she’d ever seen.
“I couldn’t believe it. I got a toothbrush with no bristles,” she said. “It must have not gone through the bristle machine. It was just a stick.”
To most patients, a useless hospital toothbrush would be a mild inconvenience. But to Dr. Giuliano, a nursing professor at the University of Massachusetts, Amherst, it was a reminder of a pervasive “blind spot” in U.S. hospitals: the stunning consequences of unbrushed teeth.
Hospital patients not getting their teeth brushed, or not brushing their teeth themselves, is believed to be a leading cause of hundreds of thousands of cases of pneumonia a year in patients who have not been put on a ventilator. Pneumonia is among the most common infections that occur in health care facilities, and a majority of cases are nonventilator hospital-acquired pneumonia, or NVHAP, which kills up to 30% of those infected, Dr. Giuliano and other experts said.
But unlike many infections that strike within hospitals, the federal government doesn’t require hospitals to report cases of NVHAP. As a result, few hospitals understand the origin of the illness, track its occurrence, or actively work to prevent it, the experts said.
, according to a growing body of peer-reviewed research papers. Instead, many hospitals often skip teeth brushing to prioritize other tasks and provide only cheap, ineffective toothbrushes, often unaware of the consequences, said Dr. Dian Baker, a Sacramento (Calif.) State nursing professor who has spent more than a decade studying NVHAP.
“I’ll tell you that today the vast majority of the tens of thousands of nurses in hospitals have no idea that pneumonia comes from germs in the mouth,” Dr. Baker said.
Pneumonia occurs when germs trigger an infection in the lungs. Although NVHAP accounts for most of the cases that occur in hospitals, it historically has not received the same attention as pneumonia tied to ventilators, which is easier to identify and study because it occurs among a narrow subset of patients.
NVHAP, a risk for virtually all hospital patients, is often caused by bacteria from the mouth that gathers in the scummy biofilm on unbrushed teeth and is aspirated into the lungs. Patients face a higher risk if they lie flat or remain immobile for long periods, so NVHAP can also be prevented by elevating their heads and getting them out of bed more often.
According to the National Organization for NV-HAP Prevention, which was founded in 2020, this pneumonia infects about 1 in every 100 hospital patients and kills 15%-30% of them. For those who survive, the illness often extends their hospital stay by up to 15 days and makes it much more likely they will be readmitted within a month or transferred to an intensive care unit.
John McCleary, 83, of Millinocket, Maine, contracted a likely case of NVHAP in 2008 after he fractured his ankle in a fall and spent 12 days in rehabilitation at a hospital, said his daughter, Kathy Day, a retired nurse and advocate with the Patient Safety Action Network.
Mr. McCleary recovered from the fracture but not from pneumonia. Two days after he returned home, the infection in his lungs caused him to be rushed back to the hospital, where he went into sepsis and spent weeks in treatment before moving to an isolation unit in a nursing home.
He died weeks later, emaciated, largely deaf, unable to eat, and often “too weak to get water through a straw,” his daughter said. After contracting pneumonia, he never walked again.
“It was an astounding assault on his body, from him being here visiting me the week before his fall, to his death just a few months later,” Ms. Day said. “And the whole thing was avoidable.”
While experts describe NVHAP as a largely ignored threat, that appears to be changing.
Last year, a group of researchers – including Dr. Giuliano and Dr. Baker, plus officials from the Centers for Disease Control and Prevention, the Veterans Health Administration, and the Joint Commission – published a “call-to-action” research paper hoping to launch “a national health care conversation about NVHAP prevention.”
The Joint Commission, a nonprofit organization whose accreditation can make or break hospitals, is considering broadening the infection control standards to include more ailments, including NVHAP, said Sylvia Garcia-Houchins, its director of infection prevention and control.
Separately, ECRI, a nonprofit focused on health care safety, this year pinpointed NVHAP as one of its top patient safety concerns.
James Davis, an ECRI infection expert, said the prevalence of NVHAP, while already alarming, is likely “underestimated” and probably worsened as hospitals swelled with patients during the coronavirus pandemic.
“We only know what’s reported,” Mr. Davis said. “Could this be the tip of the iceberg? I would say, in my opinion, probably.”
To better measure the condition, some researchers call for a standardized surveillance definition of NVHAP, which could in time open the door for the federal government to mandate reporting of cases or incentivize prevention. With increasing urgency, researchers are pushing for hospitals not to wait for the federal government to act against NVHAP.
Dr. Baker said she has spoken with hundreds of hospitals about how to prevent NVHAP, but thousands more have yet to take up the cause.
“We are not asking for some big, $300,000 piece of equipment,” Dr. Baker said. “The two things that show the best evidence of preventing this harm are things that should be happening in standard care anyway – brushing teeth and getting patients mobilized.”
That evidence comes from a smattering of studies that show those two strategies can lead to sharp reductions in infection rates.
In California, a study at 21 Kaiser Permanente hospitals used a reprioritization of oral care and getting patients out of bed to reduce rates of hospital-acquired pneumonia by around 70%. At Sutter Medical Center in Sacramento, better oral care reduced NVHAP cases by a yearly average of 35%.
At Orlando Regional Medical Center in Florida, a medical unit and a surgical unit where patients received enhanced oral care reduced NVHAP rates by 85% and 56%, respectively, when compared with similar units that received normal care. A similar study is underway at two hospitals in Illinois.
And the most compelling results come from a veterans’ hospital in Salem, Va., where a 2016 oral care pilot program reduced rates of NVHAP by 92% – saving an estimated 13 lives in just 19 months. The program, the HAPPEN Initiative, has been expanded across the Veterans Health Administration, and experts say it could serve as a model for all U.S. hospitals.
Dr. Michelle Lucatorto, a nursing official who leads HAPPEN, said the program trains nurses to most effectively brush patients’ teeth and educates patients and families on the link between oral care and preventing NVHAP. While teeth brushing may not seem to require training, Dr. Lucatorto made comparisons to how the coronavirus revealed many Americans were doing a lackluster job of another routine hygienic practice: washing their hands.
“Sometimes we are searching for the most complicated intervention,” she said. “We are always looking for that new bypass surgery, or some new technical equipment. And sometimes I think we fail to look at the simple things we can do in our practice to save people’s lives.”
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.
Four years ago, when Dr. Karen Giuliano went to a Boston hospital for hip replacement surgery, she was given a pale-pink bucket of toiletries issued to patients in many hospitals. Inside were tissues, bar soap, deodorant, toothpaste, and, without a doubt, the worst toothbrush she’d ever seen.
“I couldn’t believe it. I got a toothbrush with no bristles,” she said. “It must have not gone through the bristle machine. It was just a stick.”
To most patients, a useless hospital toothbrush would be a mild inconvenience. But to Dr. Giuliano, a nursing professor at the University of Massachusetts, Amherst, it was a reminder of a pervasive “blind spot” in U.S. hospitals: the stunning consequences of unbrushed teeth.
Hospital patients not getting their teeth brushed, or not brushing their teeth themselves, is believed to be a leading cause of hundreds of thousands of cases of pneumonia a year in patients who have not been put on a ventilator. Pneumonia is among the most common infections that occur in health care facilities, and a majority of cases are nonventilator hospital-acquired pneumonia, or NVHAP, which kills up to 30% of those infected, Dr. Giuliano and other experts said.
But unlike many infections that strike within hospitals, the federal government doesn’t require hospitals to report cases of NVHAP. As a result, few hospitals understand the origin of the illness, track its occurrence, or actively work to prevent it, the experts said.
, according to a growing body of peer-reviewed research papers. Instead, many hospitals often skip teeth brushing to prioritize other tasks and provide only cheap, ineffective toothbrushes, often unaware of the consequences, said Dr. Dian Baker, a Sacramento (Calif.) State nursing professor who has spent more than a decade studying NVHAP.
“I’ll tell you that today the vast majority of the tens of thousands of nurses in hospitals have no idea that pneumonia comes from germs in the mouth,” Dr. Baker said.
Pneumonia occurs when germs trigger an infection in the lungs. Although NVHAP accounts for most of the cases that occur in hospitals, it historically has not received the same attention as pneumonia tied to ventilators, which is easier to identify and study because it occurs among a narrow subset of patients.
NVHAP, a risk for virtually all hospital patients, is often caused by bacteria from the mouth that gathers in the scummy biofilm on unbrushed teeth and is aspirated into the lungs. Patients face a higher risk if they lie flat or remain immobile for long periods, so NVHAP can also be prevented by elevating their heads and getting them out of bed more often.
According to the National Organization for NV-HAP Prevention, which was founded in 2020, this pneumonia infects about 1 in every 100 hospital patients and kills 15%-30% of them. For those who survive, the illness often extends their hospital stay by up to 15 days and makes it much more likely they will be readmitted within a month or transferred to an intensive care unit.
John McCleary, 83, of Millinocket, Maine, contracted a likely case of NVHAP in 2008 after he fractured his ankle in a fall and spent 12 days in rehabilitation at a hospital, said his daughter, Kathy Day, a retired nurse and advocate with the Patient Safety Action Network.
Mr. McCleary recovered from the fracture but not from pneumonia. Two days after he returned home, the infection in his lungs caused him to be rushed back to the hospital, where he went into sepsis and spent weeks in treatment before moving to an isolation unit in a nursing home.
He died weeks later, emaciated, largely deaf, unable to eat, and often “too weak to get water through a straw,” his daughter said. After contracting pneumonia, he never walked again.
“It was an astounding assault on his body, from him being here visiting me the week before his fall, to his death just a few months later,” Ms. Day said. “And the whole thing was avoidable.”
While experts describe NVHAP as a largely ignored threat, that appears to be changing.
Last year, a group of researchers – including Dr. Giuliano and Dr. Baker, plus officials from the Centers for Disease Control and Prevention, the Veterans Health Administration, and the Joint Commission – published a “call-to-action” research paper hoping to launch “a national health care conversation about NVHAP prevention.”
The Joint Commission, a nonprofit organization whose accreditation can make or break hospitals, is considering broadening the infection control standards to include more ailments, including NVHAP, said Sylvia Garcia-Houchins, its director of infection prevention and control.
Separately, ECRI, a nonprofit focused on health care safety, this year pinpointed NVHAP as one of its top patient safety concerns.
James Davis, an ECRI infection expert, said the prevalence of NVHAP, while already alarming, is likely “underestimated” and probably worsened as hospitals swelled with patients during the coronavirus pandemic.
“We only know what’s reported,” Mr. Davis said. “Could this be the tip of the iceberg? I would say, in my opinion, probably.”
To better measure the condition, some researchers call for a standardized surveillance definition of NVHAP, which could in time open the door for the federal government to mandate reporting of cases or incentivize prevention. With increasing urgency, researchers are pushing for hospitals not to wait for the federal government to act against NVHAP.
Dr. Baker said she has spoken with hundreds of hospitals about how to prevent NVHAP, but thousands more have yet to take up the cause.
“We are not asking for some big, $300,000 piece of equipment,” Dr. Baker said. “The two things that show the best evidence of preventing this harm are things that should be happening in standard care anyway – brushing teeth and getting patients mobilized.”
That evidence comes from a smattering of studies that show those two strategies can lead to sharp reductions in infection rates.
In California, a study at 21 Kaiser Permanente hospitals used a reprioritization of oral care and getting patients out of bed to reduce rates of hospital-acquired pneumonia by around 70%. At Sutter Medical Center in Sacramento, better oral care reduced NVHAP cases by a yearly average of 35%.
At Orlando Regional Medical Center in Florida, a medical unit and a surgical unit where patients received enhanced oral care reduced NVHAP rates by 85% and 56%, respectively, when compared with similar units that received normal care. A similar study is underway at two hospitals in Illinois.
And the most compelling results come from a veterans’ hospital in Salem, Va., where a 2016 oral care pilot program reduced rates of NVHAP by 92% – saving an estimated 13 lives in just 19 months. The program, the HAPPEN Initiative, has been expanded across the Veterans Health Administration, and experts say it could serve as a model for all U.S. hospitals.
Dr. Michelle Lucatorto, a nursing official who leads HAPPEN, said the program trains nurses to most effectively brush patients’ teeth and educates patients and families on the link between oral care and preventing NVHAP. While teeth brushing may not seem to require training, Dr. Lucatorto made comparisons to how the coronavirus revealed many Americans were doing a lackluster job of another routine hygienic practice: washing their hands.
“Sometimes we are searching for the most complicated intervention,” she said. “We are always looking for that new bypass surgery, or some new technical equipment. And sometimes I think we fail to look at the simple things we can do in our practice to save people’s lives.”
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.
Four years ago, when Dr. Karen Giuliano went to a Boston hospital for hip replacement surgery, she was given a pale-pink bucket of toiletries issued to patients in many hospitals. Inside were tissues, bar soap, deodorant, toothpaste, and, without a doubt, the worst toothbrush she’d ever seen.
“I couldn’t believe it. I got a toothbrush with no bristles,” she said. “It must have not gone through the bristle machine. It was just a stick.”
To most patients, a useless hospital toothbrush would be a mild inconvenience. But to Dr. Giuliano, a nursing professor at the University of Massachusetts, Amherst, it was a reminder of a pervasive “blind spot” in U.S. hospitals: the stunning consequences of unbrushed teeth.
Hospital patients not getting their teeth brushed, or not brushing their teeth themselves, is believed to be a leading cause of hundreds of thousands of cases of pneumonia a year in patients who have not been put on a ventilator. Pneumonia is among the most common infections that occur in health care facilities, and a majority of cases are nonventilator hospital-acquired pneumonia, or NVHAP, which kills up to 30% of those infected, Dr. Giuliano and other experts said.
But unlike many infections that strike within hospitals, the federal government doesn’t require hospitals to report cases of NVHAP. As a result, few hospitals understand the origin of the illness, track its occurrence, or actively work to prevent it, the experts said.
, according to a growing body of peer-reviewed research papers. Instead, many hospitals often skip teeth brushing to prioritize other tasks and provide only cheap, ineffective toothbrushes, often unaware of the consequences, said Dr. Dian Baker, a Sacramento (Calif.) State nursing professor who has spent more than a decade studying NVHAP.
“I’ll tell you that today the vast majority of the tens of thousands of nurses in hospitals have no idea that pneumonia comes from germs in the mouth,” Dr. Baker said.
Pneumonia occurs when germs trigger an infection in the lungs. Although NVHAP accounts for most of the cases that occur in hospitals, it historically has not received the same attention as pneumonia tied to ventilators, which is easier to identify and study because it occurs among a narrow subset of patients.
NVHAP, a risk for virtually all hospital patients, is often caused by bacteria from the mouth that gathers in the scummy biofilm on unbrushed teeth and is aspirated into the lungs. Patients face a higher risk if they lie flat or remain immobile for long periods, so NVHAP can also be prevented by elevating their heads and getting them out of bed more often.
According to the National Organization for NV-HAP Prevention, which was founded in 2020, this pneumonia infects about 1 in every 100 hospital patients and kills 15%-30% of them. For those who survive, the illness often extends their hospital stay by up to 15 days and makes it much more likely they will be readmitted within a month or transferred to an intensive care unit.
John McCleary, 83, of Millinocket, Maine, contracted a likely case of NVHAP in 2008 after he fractured his ankle in a fall and spent 12 days in rehabilitation at a hospital, said his daughter, Kathy Day, a retired nurse and advocate with the Patient Safety Action Network.
Mr. McCleary recovered from the fracture but not from pneumonia. Two days after he returned home, the infection in his lungs caused him to be rushed back to the hospital, where he went into sepsis and spent weeks in treatment before moving to an isolation unit in a nursing home.
He died weeks later, emaciated, largely deaf, unable to eat, and often “too weak to get water through a straw,” his daughter said. After contracting pneumonia, he never walked again.
“It was an astounding assault on his body, from him being here visiting me the week before his fall, to his death just a few months later,” Ms. Day said. “And the whole thing was avoidable.”
While experts describe NVHAP as a largely ignored threat, that appears to be changing.
Last year, a group of researchers – including Dr. Giuliano and Dr. Baker, plus officials from the Centers for Disease Control and Prevention, the Veterans Health Administration, and the Joint Commission – published a “call-to-action” research paper hoping to launch “a national health care conversation about NVHAP prevention.”
The Joint Commission, a nonprofit organization whose accreditation can make or break hospitals, is considering broadening the infection control standards to include more ailments, including NVHAP, said Sylvia Garcia-Houchins, its director of infection prevention and control.
Separately, ECRI, a nonprofit focused on health care safety, this year pinpointed NVHAP as one of its top patient safety concerns.
James Davis, an ECRI infection expert, said the prevalence of NVHAP, while already alarming, is likely “underestimated” and probably worsened as hospitals swelled with patients during the coronavirus pandemic.
“We only know what’s reported,” Mr. Davis said. “Could this be the tip of the iceberg? I would say, in my opinion, probably.”
To better measure the condition, some researchers call for a standardized surveillance definition of NVHAP, which could in time open the door for the federal government to mandate reporting of cases or incentivize prevention. With increasing urgency, researchers are pushing for hospitals not to wait for the federal government to act against NVHAP.
Dr. Baker said she has spoken with hundreds of hospitals about how to prevent NVHAP, but thousands more have yet to take up the cause.
“We are not asking for some big, $300,000 piece of equipment,” Dr. Baker said. “The two things that show the best evidence of preventing this harm are things that should be happening in standard care anyway – brushing teeth and getting patients mobilized.”
That evidence comes from a smattering of studies that show those two strategies can lead to sharp reductions in infection rates.
In California, a study at 21 Kaiser Permanente hospitals used a reprioritization of oral care and getting patients out of bed to reduce rates of hospital-acquired pneumonia by around 70%. At Sutter Medical Center in Sacramento, better oral care reduced NVHAP cases by a yearly average of 35%.
At Orlando Regional Medical Center in Florida, a medical unit and a surgical unit where patients received enhanced oral care reduced NVHAP rates by 85% and 56%, respectively, when compared with similar units that received normal care. A similar study is underway at two hospitals in Illinois.
And the most compelling results come from a veterans’ hospital in Salem, Va., where a 2016 oral care pilot program reduced rates of NVHAP by 92% – saving an estimated 13 lives in just 19 months. The program, the HAPPEN Initiative, has been expanded across the Veterans Health Administration, and experts say it could serve as a model for all U.S. hospitals.
Dr. Michelle Lucatorto, a nursing official who leads HAPPEN, said the program trains nurses to most effectively brush patients’ teeth and educates patients and families on the link between oral care and preventing NVHAP. While teeth brushing may not seem to require training, Dr. Lucatorto made comparisons to how the coronavirus revealed many Americans were doing a lackluster job of another routine hygienic practice: washing their hands.
“Sometimes we are searching for the most complicated intervention,” she said. “We are always looking for that new bypass surgery, or some new technical equipment. And sometimes I think we fail to look at the simple things we can do in our practice to save people’s lives.”
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.
Uveitis in juvenile arthritis patients persists into midlife
Active uveitis remained in 43.4% of juvenile idiopathic arthritis (JIA) patients up to 40 years after a diagnosis, based on data from 30 individuals.
Uveitis occurs in approximately 10%-20% of patients with JIA, but data on the long-term activity and prevalence are limited, although previous studies suggest that uveitis can persist into adulthood, wrote Dr. Angelika Skarin of Skåne University in Lund, Sweden, and colleagues.
In a study published in Pediatric Rheumatology, the researchers reviewed ophthalmic records from 30 JIA patients at a mean of 40.7 years after uveitis onset. They compared these records to data collected from the same patient population at a mean of 7.2 and 24.0 years after onset. In the previous follow-up studies, 49% of the patients had active uveitis at 24 years, and the prevalence of cataracts and glaucoma increased between the 7-year and 24-year assessments.
In the current study, 43.4% of the population had active uveitis at the 40-year follow-up, which corresponded to 23.6% of the original study cohort. The mean age of the participants overall was 46.9 years, the mean duration of joint disease was 42.99 years, and the mean time from onset of uveitis was 40.7 years.
In addition, 66.6% of the patients in the current study had cataracts or had undergone cataract surgery in one or both eyes, and 40.0% had glaucoma.
By the time of the current study, of the original cohort of 55 individuals, 11 were deceased; rheumatic disease was declared the main cause in four patients and a contributing factor in three others.
Potential drivers of the earliest cases of glaucoma and ocular hypertension (G/OH) include increased intraocular pressure as a result of topical corticosteroid treatment, the researchers noted in their discussion. However, G/OH occurring later than the 7-year follow-up was “more likely to be the type observed in many patients with long-standing chronic uveitis, where a gradual increase in intraocular pressure is assumed to be caused by impaired aqueous outflow,” they said.
Only 4 of the 30 patients did not have regular ophthalmology visits, which suggests a study population with ocular symptoms or concerns about their eyesight, the researchers wrote. “The fact that 13% of our original cohort were reported to have severe visual impairment or worse in both eyes at any of the three follow-ups is noteworthy,” compared to reports of visual impairment of less than 0.5% in a German study in the general population for similar ages.
The findings were limited by several factors, including the retrospective design, small study population, and lack of data on 25 of the original 55-member study cohort, which may reduce the reliability of the current study, the researchers noted. However, the results reflect data from previous studies and support the need for JIA patients to continue regular ophthalmic checkups throughout life, they concluded.
The study was supported by Stiftelsen för Synskadade i f.d. Malmöhus län, Sweden, Skånes Universitetssjukhus Stiftelser och Donationer, Ögonfonden, and the Swedish Society of Medicine. The researchers had no financial conflicts to disclose.
Active uveitis remained in 43.4% of juvenile idiopathic arthritis (JIA) patients up to 40 years after a diagnosis, based on data from 30 individuals.
Uveitis occurs in approximately 10%-20% of patients with JIA, but data on the long-term activity and prevalence are limited, although previous studies suggest that uveitis can persist into adulthood, wrote Dr. Angelika Skarin of Skåne University in Lund, Sweden, and colleagues.
In a study published in Pediatric Rheumatology, the researchers reviewed ophthalmic records from 30 JIA patients at a mean of 40.7 years after uveitis onset. They compared these records to data collected from the same patient population at a mean of 7.2 and 24.0 years after onset. In the previous follow-up studies, 49% of the patients had active uveitis at 24 years, and the prevalence of cataracts and glaucoma increased between the 7-year and 24-year assessments.
In the current study, 43.4% of the population had active uveitis at the 40-year follow-up, which corresponded to 23.6% of the original study cohort. The mean age of the participants overall was 46.9 years, the mean duration of joint disease was 42.99 years, and the mean time from onset of uveitis was 40.7 years.
In addition, 66.6% of the patients in the current study had cataracts or had undergone cataract surgery in one or both eyes, and 40.0% had glaucoma.
By the time of the current study, of the original cohort of 55 individuals, 11 were deceased; rheumatic disease was declared the main cause in four patients and a contributing factor in three others.
Potential drivers of the earliest cases of glaucoma and ocular hypertension (G/OH) include increased intraocular pressure as a result of topical corticosteroid treatment, the researchers noted in their discussion. However, G/OH occurring later than the 7-year follow-up was “more likely to be the type observed in many patients with long-standing chronic uveitis, where a gradual increase in intraocular pressure is assumed to be caused by impaired aqueous outflow,” they said.
Only 4 of the 30 patients did not have regular ophthalmology visits, which suggests a study population with ocular symptoms or concerns about their eyesight, the researchers wrote. “The fact that 13% of our original cohort were reported to have severe visual impairment or worse in both eyes at any of the three follow-ups is noteworthy,” compared to reports of visual impairment of less than 0.5% in a German study in the general population for similar ages.
The findings were limited by several factors, including the retrospective design, small study population, and lack of data on 25 of the original 55-member study cohort, which may reduce the reliability of the current study, the researchers noted. However, the results reflect data from previous studies and support the need for JIA patients to continue regular ophthalmic checkups throughout life, they concluded.
The study was supported by Stiftelsen för Synskadade i f.d. Malmöhus län, Sweden, Skånes Universitetssjukhus Stiftelser och Donationer, Ögonfonden, and the Swedish Society of Medicine. The researchers had no financial conflicts to disclose.
Active uveitis remained in 43.4% of juvenile idiopathic arthritis (JIA) patients up to 40 years after a diagnosis, based on data from 30 individuals.
Uveitis occurs in approximately 10%-20% of patients with JIA, but data on the long-term activity and prevalence are limited, although previous studies suggest that uveitis can persist into adulthood, wrote Dr. Angelika Skarin of Skåne University in Lund, Sweden, and colleagues.
In a study published in Pediatric Rheumatology, the researchers reviewed ophthalmic records from 30 JIA patients at a mean of 40.7 years after uveitis onset. They compared these records to data collected from the same patient population at a mean of 7.2 and 24.0 years after onset. In the previous follow-up studies, 49% of the patients had active uveitis at 24 years, and the prevalence of cataracts and glaucoma increased between the 7-year and 24-year assessments.
In the current study, 43.4% of the population had active uveitis at the 40-year follow-up, which corresponded to 23.6% of the original study cohort. The mean age of the participants overall was 46.9 years, the mean duration of joint disease was 42.99 years, and the mean time from onset of uveitis was 40.7 years.
In addition, 66.6% of the patients in the current study had cataracts or had undergone cataract surgery in one or both eyes, and 40.0% had glaucoma.
By the time of the current study, of the original cohort of 55 individuals, 11 were deceased; rheumatic disease was declared the main cause in four patients and a contributing factor in three others.
Potential drivers of the earliest cases of glaucoma and ocular hypertension (G/OH) include increased intraocular pressure as a result of topical corticosteroid treatment, the researchers noted in their discussion. However, G/OH occurring later than the 7-year follow-up was “more likely to be the type observed in many patients with long-standing chronic uveitis, where a gradual increase in intraocular pressure is assumed to be caused by impaired aqueous outflow,” they said.
Only 4 of the 30 patients did not have regular ophthalmology visits, which suggests a study population with ocular symptoms or concerns about their eyesight, the researchers wrote. “The fact that 13% of our original cohort were reported to have severe visual impairment or worse in both eyes at any of the three follow-ups is noteworthy,” compared to reports of visual impairment of less than 0.5% in a German study in the general population for similar ages.
The findings were limited by several factors, including the retrospective design, small study population, and lack of data on 25 of the original 55-member study cohort, which may reduce the reliability of the current study, the researchers noted. However, the results reflect data from previous studies and support the need for JIA patients to continue regular ophthalmic checkups throughout life, they concluded.
The study was supported by Stiftelsen för Synskadade i f.d. Malmöhus län, Sweden, Skånes Universitetssjukhus Stiftelser och Donationer, Ögonfonden, and the Swedish Society of Medicine. The researchers had no financial conflicts to disclose.
FROM PEDIATRIC RHEUMATOLOGY
Pulse oximeters lead to less oxygen supplementation for people of color
The new research suggests that skin color–related differences in pulse oximeter readings are in fact impacting clinical decision-making, lead author Eric R. Gottlieb, MD, of Brigham and Women’s Hospital and Massachusetts Institute of Technology, both in Boston, and colleagues wrote. This suggests that technology needs to updated to improve health equity, they continued, in their paper published in JAMA Internal Medicine.
“It has been known for decades that these readings are affected by various surface pigmentations, including nail polish and skin melanin, which may affect light absorption and scattering,” the investigators wrote. “This increases the risk of hidden hypoxemia [among patients with darker skin], in which patients have falsely elevated SpO2 readings, usually defined as 92% or greater, with a blood hemoglobin oxygen saturation less than 88%.”
Although published reports on this phenomenon date back to the 1980s, clinical significance has been largely discounted, they said, citing a 2008 paper on the topic, which stated that “oximetry need not have exact accuracy” to determine if a patient needs oxygen supplementation.
‘We’re not providing equal care’
Questioning the validity of this statement, Dr. Gottlieb and colleagues conducted a retrospective cohort study involving 3,069 patients admitted to intensive care at the Beth Israel Deaconess Medical Center in Boston between 2008 and 2019, thereby excluding patients treated during the COVID-19 pandemic. The population consisted of four races/ethnicities: White (87%), Black (7%), Hispanic (4%), and Asian (3%).
Aligning with previous studies, multivariable linear regression analyses showed that Asian, Black, and Hispanic patients had significantly higher SpO2 readings than White patients in relation to hemoglobin oxygen saturation values, suggesting falsely elevated readings.
Further modeling showed that these same patient groups also received lower oxygen delivery rates, which were not explained directly by race/ethnicity, but instead were mediated by the discrepancy between SpO2 and hemoglobin oxygen saturation values. In other words, physicians were responding consistently to pulse oximetry readings, rather than exhibiting a direct racial/ethnic bias in their clinical decision-making.
“We’re not providing equal care,” Dr. Gottlieb said in an interview. “It’s not that the patients are sicker, or have other socioeconomic explanations for why this happens to them. It’s us. It’s our technology. And that’s something that really has to be fixed.”
The investigators offered a cautionary view of corrective algorithms, as these “have exacerbated disparities and are subject to ethical concerns;” for example, with glomerular filtration rate estimations in Black patients.
Dr. Gottlieb also cautioned against action by individual physicians, who may now be inclined to change how they interpret pulse oximeter readings based on a patient’s race or ethnicity.
“I don’t think that we can expect physicians, every time they see a patient, to be second guessing whether the number basically reflects the truth,” he said.
Instead, Dr. Gottlieb suggested that the burden of change rests upon the shoulders of institutions, including hospitals and device manufacturers, both of which “really need to take the responsibility” for making sure that pulse oximeters are “equitable and have similar performance across races.”
While Dr. Gottlieb said that skin color likely plays the greatest role in measurement discrepancies, he encouraged stakeholders “to think broadly about this, and not just assume that it’s entirely skin color,” noting a small amount of evidence indicating that blood chemistry may also play a role. Still, he predicted that colorimetry – the direct measurement of skin color – will probably be incorporated into pulse oximeters of the future.
Black patients 3X more likely to have hidden hypoxia than White patients
Michael Sjoding, MD, of the University of Michigan, Ann Arbor, was one of the first to raise awareness of skin color–related issues with pulse oximeters during the throes of the COVID-19 pandemic. His study, which involved more than 10,000 patients, showed that Black patients were threefold more likely to have hidden hypoxia than White patients.
The present study shows that such discrepancies are indeed clinically significant, Dr. Sjoding said in an interview. And these data are needed, he added, to bring about change.
“What is being asked is potentially a big deal,” Dr. Sjoding said. “Pulse oximeters are everywhere, and it would be a big undertaking to redesign pulse oximeters and purchase new pulse oximeters. You need a compelling body of evidence to do that. I think it’s there now, clearly. So I’m hopeful that we’re going to finally move forward, towards having devices that we are confident work accurately in everyone.”
Why it has taken so long to gather this evidence, however, is a thornier topic, considering race-related discrepancies in pulse oximeter readings were first documented more than 3 decades ago.
“We sort of rediscovered something that had been known and had been described in the past,” Dr. Sjoding said. He explained how he and many of his colleagues had completed pulmonary fellowships, yet none of them knew of these potential issues with pulse oximeters until they began to observe differences in their own patients during the pandemic.
“I’ll give previous generations of researchers the benefit of the doubt,” Dr. Sjoding said, pointing out that techniques in data gathering and analysis have advanced considerably over the years. “The types of studies that were done before were very different than what we did.”
Yet Dr. Sjoding entertained the possibility that other factors may have been at play.
“I think definitely there’s a social commentary on prioritization of research,” he said.
The study was supported by grants from the National Institutes of Health. The investigators and Dr. Sjoding reported no conflicts of interest.
The new research suggests that skin color–related differences in pulse oximeter readings are in fact impacting clinical decision-making, lead author Eric R. Gottlieb, MD, of Brigham and Women’s Hospital and Massachusetts Institute of Technology, both in Boston, and colleagues wrote. This suggests that technology needs to updated to improve health equity, they continued, in their paper published in JAMA Internal Medicine.
“It has been known for decades that these readings are affected by various surface pigmentations, including nail polish and skin melanin, which may affect light absorption and scattering,” the investigators wrote. “This increases the risk of hidden hypoxemia [among patients with darker skin], in which patients have falsely elevated SpO2 readings, usually defined as 92% or greater, with a blood hemoglobin oxygen saturation less than 88%.”
Although published reports on this phenomenon date back to the 1980s, clinical significance has been largely discounted, they said, citing a 2008 paper on the topic, which stated that “oximetry need not have exact accuracy” to determine if a patient needs oxygen supplementation.
‘We’re not providing equal care’
Questioning the validity of this statement, Dr. Gottlieb and colleagues conducted a retrospective cohort study involving 3,069 patients admitted to intensive care at the Beth Israel Deaconess Medical Center in Boston between 2008 and 2019, thereby excluding patients treated during the COVID-19 pandemic. The population consisted of four races/ethnicities: White (87%), Black (7%), Hispanic (4%), and Asian (3%).
Aligning with previous studies, multivariable linear regression analyses showed that Asian, Black, and Hispanic patients had significantly higher SpO2 readings than White patients in relation to hemoglobin oxygen saturation values, suggesting falsely elevated readings.
Further modeling showed that these same patient groups also received lower oxygen delivery rates, which were not explained directly by race/ethnicity, but instead were mediated by the discrepancy between SpO2 and hemoglobin oxygen saturation values. In other words, physicians were responding consistently to pulse oximetry readings, rather than exhibiting a direct racial/ethnic bias in their clinical decision-making.
“We’re not providing equal care,” Dr. Gottlieb said in an interview. “It’s not that the patients are sicker, or have other socioeconomic explanations for why this happens to them. It’s us. It’s our technology. And that’s something that really has to be fixed.”
The investigators offered a cautionary view of corrective algorithms, as these “have exacerbated disparities and are subject to ethical concerns;” for example, with glomerular filtration rate estimations in Black patients.
Dr. Gottlieb also cautioned against action by individual physicians, who may now be inclined to change how they interpret pulse oximeter readings based on a patient’s race or ethnicity.
“I don’t think that we can expect physicians, every time they see a patient, to be second guessing whether the number basically reflects the truth,” he said.
Instead, Dr. Gottlieb suggested that the burden of change rests upon the shoulders of institutions, including hospitals and device manufacturers, both of which “really need to take the responsibility” for making sure that pulse oximeters are “equitable and have similar performance across races.”
While Dr. Gottlieb said that skin color likely plays the greatest role in measurement discrepancies, he encouraged stakeholders “to think broadly about this, and not just assume that it’s entirely skin color,” noting a small amount of evidence indicating that blood chemistry may also play a role. Still, he predicted that colorimetry – the direct measurement of skin color – will probably be incorporated into pulse oximeters of the future.
Black patients 3X more likely to have hidden hypoxia than White patients
Michael Sjoding, MD, of the University of Michigan, Ann Arbor, was one of the first to raise awareness of skin color–related issues with pulse oximeters during the throes of the COVID-19 pandemic. His study, which involved more than 10,000 patients, showed that Black patients were threefold more likely to have hidden hypoxia than White patients.
The present study shows that such discrepancies are indeed clinically significant, Dr. Sjoding said in an interview. And these data are needed, he added, to bring about change.
“What is being asked is potentially a big deal,” Dr. Sjoding said. “Pulse oximeters are everywhere, and it would be a big undertaking to redesign pulse oximeters and purchase new pulse oximeters. You need a compelling body of evidence to do that. I think it’s there now, clearly. So I’m hopeful that we’re going to finally move forward, towards having devices that we are confident work accurately in everyone.”
Why it has taken so long to gather this evidence, however, is a thornier topic, considering race-related discrepancies in pulse oximeter readings were first documented more than 3 decades ago.
“We sort of rediscovered something that had been known and had been described in the past,” Dr. Sjoding said. He explained how he and many of his colleagues had completed pulmonary fellowships, yet none of them knew of these potential issues with pulse oximeters until they began to observe differences in their own patients during the pandemic.
“I’ll give previous generations of researchers the benefit of the doubt,” Dr. Sjoding said, pointing out that techniques in data gathering and analysis have advanced considerably over the years. “The types of studies that were done before were very different than what we did.”
Yet Dr. Sjoding entertained the possibility that other factors may have been at play.
“I think definitely there’s a social commentary on prioritization of research,” he said.
The study was supported by grants from the National Institutes of Health. The investigators and Dr. Sjoding reported no conflicts of interest.
The new research suggests that skin color–related differences in pulse oximeter readings are in fact impacting clinical decision-making, lead author Eric R. Gottlieb, MD, of Brigham and Women’s Hospital and Massachusetts Institute of Technology, both in Boston, and colleagues wrote. This suggests that technology needs to updated to improve health equity, they continued, in their paper published in JAMA Internal Medicine.
“It has been known for decades that these readings are affected by various surface pigmentations, including nail polish and skin melanin, which may affect light absorption and scattering,” the investigators wrote. “This increases the risk of hidden hypoxemia [among patients with darker skin], in which patients have falsely elevated SpO2 readings, usually defined as 92% or greater, with a blood hemoglobin oxygen saturation less than 88%.”
Although published reports on this phenomenon date back to the 1980s, clinical significance has been largely discounted, they said, citing a 2008 paper on the topic, which stated that “oximetry need not have exact accuracy” to determine if a patient needs oxygen supplementation.
‘We’re not providing equal care’
Questioning the validity of this statement, Dr. Gottlieb and colleagues conducted a retrospective cohort study involving 3,069 patients admitted to intensive care at the Beth Israel Deaconess Medical Center in Boston between 2008 and 2019, thereby excluding patients treated during the COVID-19 pandemic. The population consisted of four races/ethnicities: White (87%), Black (7%), Hispanic (4%), and Asian (3%).
Aligning with previous studies, multivariable linear regression analyses showed that Asian, Black, and Hispanic patients had significantly higher SpO2 readings than White patients in relation to hemoglobin oxygen saturation values, suggesting falsely elevated readings.
Further modeling showed that these same patient groups also received lower oxygen delivery rates, which were not explained directly by race/ethnicity, but instead were mediated by the discrepancy between SpO2 and hemoglobin oxygen saturation values. In other words, physicians were responding consistently to pulse oximetry readings, rather than exhibiting a direct racial/ethnic bias in their clinical decision-making.
“We’re not providing equal care,” Dr. Gottlieb said in an interview. “It’s not that the patients are sicker, or have other socioeconomic explanations for why this happens to them. It’s us. It’s our technology. And that’s something that really has to be fixed.”
The investigators offered a cautionary view of corrective algorithms, as these “have exacerbated disparities and are subject to ethical concerns;” for example, with glomerular filtration rate estimations in Black patients.
Dr. Gottlieb also cautioned against action by individual physicians, who may now be inclined to change how they interpret pulse oximeter readings based on a patient’s race or ethnicity.
“I don’t think that we can expect physicians, every time they see a patient, to be second guessing whether the number basically reflects the truth,” he said.
Instead, Dr. Gottlieb suggested that the burden of change rests upon the shoulders of institutions, including hospitals and device manufacturers, both of which “really need to take the responsibility” for making sure that pulse oximeters are “equitable and have similar performance across races.”
While Dr. Gottlieb said that skin color likely plays the greatest role in measurement discrepancies, he encouraged stakeholders “to think broadly about this, and not just assume that it’s entirely skin color,” noting a small amount of evidence indicating that blood chemistry may also play a role. Still, he predicted that colorimetry – the direct measurement of skin color – will probably be incorporated into pulse oximeters of the future.
Black patients 3X more likely to have hidden hypoxia than White patients
Michael Sjoding, MD, of the University of Michigan, Ann Arbor, was one of the first to raise awareness of skin color–related issues with pulse oximeters during the throes of the COVID-19 pandemic. His study, which involved more than 10,000 patients, showed that Black patients were threefold more likely to have hidden hypoxia than White patients.
The present study shows that such discrepancies are indeed clinically significant, Dr. Sjoding said in an interview. And these data are needed, he added, to bring about change.
“What is being asked is potentially a big deal,” Dr. Sjoding said. “Pulse oximeters are everywhere, and it would be a big undertaking to redesign pulse oximeters and purchase new pulse oximeters. You need a compelling body of evidence to do that. I think it’s there now, clearly. So I’m hopeful that we’re going to finally move forward, towards having devices that we are confident work accurately in everyone.”
Why it has taken so long to gather this evidence, however, is a thornier topic, considering race-related discrepancies in pulse oximeter readings were first documented more than 3 decades ago.
“We sort of rediscovered something that had been known and had been described in the past,” Dr. Sjoding said. He explained how he and many of his colleagues had completed pulmonary fellowships, yet none of them knew of these potential issues with pulse oximeters until they began to observe differences in their own patients during the pandemic.
“I’ll give previous generations of researchers the benefit of the doubt,” Dr. Sjoding said, pointing out that techniques in data gathering and analysis have advanced considerably over the years. “The types of studies that were done before were very different than what we did.”
Yet Dr. Sjoding entertained the possibility that other factors may have been at play.
“I think definitely there’s a social commentary on prioritization of research,” he said.
The study was supported by grants from the National Institutes of Health. The investigators and Dr. Sjoding reported no conflicts of interest.
FROM JAMA INTERNAL MEDICINE
Physicians urged to write indications on drug scripts as methotrexate users face new barriers with SCOTUS decision
.
The Court’s 5-4 decision in Dobbs v. Jackson Women’s Health Organization, which halted abortion procedures across the country, also appears to be affecting certain drug regimens. Reports have emerged that pharmacies are denying access to methotrexate (MTX), a drug often used in patients with arthritis or cancer, as well as psoriasis and other skin diseases. In very high doses, MTX it is used to terminate an ectopic pregnancy after miscarriage. The drug can also lead to birth defects.
“It’s happening all over,” Donald Miller, PharmD, professor of pharmacy practice at North Dakota State University, Fargo, said in an interview. “Pharmacists are reluctant to dispense it, and rheumatologists are reluctant to prescribe it because they’re afraid of going to jail.”
Becky Schwartz, a patient who takes MTX for lupus, recently tweeted that her physician’s office stopped prescribing the drug because it is considered an abortifacient. “I had care that made my disabled life easier, and [the Supreme Court] took that from me,” Ms. Schwartz wrote.
Prior to the Supreme Court’s ruling, physicians were concerned about the impact an overturning of the 1973 law would have on patient access to MTX and other prescription medications with abortifacient properties. Doctors in general are becoming afraid of prescribing anything that’s a teratogen, said Dr. Miller.
MTX is used far more often for autoimmune disease than as an abortifacient, said rheumatologist Kristen Young, MD, clinical assistant professor at the University of Arizona College of Medicine, Phoenix. It’s a slippery slope if states reacting to the Supreme Court ruling start regulating oral abortifacients, she added. Specifically, this will have a significant impact on patients with rheumatic disease.
Texas pharmacies target two drugs
MTX denials have caught the attention of health care organizations. “Uncertainty in financial and criminal liability for health care professionals in certain state laws and regulations are possibly compromising continuity of care and access [to] medications proven to be safe and effective by the Food and Drug Administration for these indications,” warned the American Pharmacists Association (APhA) in a statement to this news organization.
The APhA said that it was monitoring this situation to assess the effect on patients and pharmacists.
The Arthritis Foundation was made aware of challenges from patients in accessing their MTX prescription for managing their arthritis and shared a statement on the Foundation’s website.
In Texas, pharmacists can refuse to fill scripts for misoprostol and MTX, a combination used for medical abortions. According to the foundation, “Already there are reports that people in Texas who miscarry or take methotrexate for arthritis [are] having trouble getting their prescriptions filled.”
MTX, approved by the FDA in 1985, “is the absolute cornerstone of rheumatoid arthritis. We cannot deny our patients this incredibly valuable drug,” said John Reveille, MD, vice-chair for the department of medicine at the University of Texas McGovern School of Medicine and a member of the Arthritis Foundation expert panel, in an interview.
“While it’s true that methotrexate can be lethal to the fetus, misoprostol is much more likely to cause a spontaneous abortion, and the combination is especially effective,” he said.
“If you look at Cochrane clinical studies, the dose of misoprostol contained in certain combinations with NSAIDs [nonsteroidal anti-inflammatory drugs] can induce spontaneous abortions. It’s surprising that pharmacists are targeting methotrexate, an essential drug in arthritis treatment, when there are medications available that do not have this benefit that can by themselves cause loss of the fetus, such as mifepristone,” added Dr. Reveille.
The Dobbs ruling could also affect the ability of oncologists to provide lifesaving cancer care, according to Jason Westin, MD, an oncologist at the University of Texas MD Anderson Cancer Center in the department of lymphoma and myeloma.
“We have heard of medications with multiple indications, such as methotrexate, not being dispensed by pharmacies due to confusion regarding the intended use and potential consequences for the health care team,” he said in an interview.
Conflicting laws pose challenges for physicians
In North Dakota, inconsistencies in several laws are making it difficult for physicians and pharmacists to make decisions. “Lots of confusion can result when people pass laws against abortion. There’s sometimes no insight into the ramifications of those laws,” said Dr. Miller.
North Dakota approved a trigger law several years ago that makes abortion illegal 30 days after an overturning of Roe. However, another law that regulates abortion conflicts with the trigger law. “Some of the language will need clarification in the next legislative session,” he said.
APhA and other pharmacy associations strongly favor not interfering with the doctor- or pharmacist-patient relationship. The law needs to defer to appropriate care between doctor and patient, said Dr. Miller. State pharmacy associations in North Dakota are working with legislatures to clarify any exceptions in the law, he added.
Arizona lawmakers are trying to reconcile two abortion laws on the books. One, based on an 1864 territorial law, deems abortion illegal. In addition, a newly approved law bans abortions after 15 weeks. The latter will go into effect in September 2022. In both laws, a risk to the mother’s life is the only exception for abortion, said Dr. Young.
Denials aren’t widespread
Not all doctors are seeing MTX denials, but they’re worried about the future. “To date, we have not encountered difficulty in obtaining methotrexate based upon state abortion restrictions but are concerned that this could occur and result in dangerous delays in care,” said Dr. Westin.
Dr. Reveille, who practices rheumatology in Houston, has not yet received any complaints from patients. Things may be different in more rural parts of Texas, where pharmacists could be denying prescriptions based on religious issues, he offered.
It’s a little soon to see what repercussions may result from the Supreme Court ruling and state actions, said Dr. Reveille. “In Texas, we’re a bit ahead of the tidal wave.”
Access problems also haven’t shown up at the university clinic where Dr. Young practices. “In Arizona, it’s unclear if there would be a legal basis to refuse a person methotrexate on the basis that it can be used as an abortifacient,” she said.
Specificity is key in writing Rx scripts
Physicians can make things easier for patients by writing the indication and dose for the drug on the prescription slip. For example, a 10-mg script for MTX is not going to be used for an abortion, said Dr. Miller.
Rheumatologists in Texas have been doing this for some time, even before the Supreme Court ruling, said Fehmida Zahabi, MD, FACR, president of the Society of Texas Association of Rheumatology. For MTX prescriptions in premenopausal women, “patients are told their doctor needs to call the pharmacist. In the small print, we are asked to give a diagnosis to make sure we aren’t using it to terminate pregnancies,” said Dr. Zahabi.
She further noted that if the diagnosis is already indicated on the script, pharmacies generally won’t give patients a hard time.
Patients can also ask their physicians for a letter of medical necessity that confirms a drug’s use for a specific medical condition.
Mail order is another option if a local pharmacy won’t fill a prescription, said Dr. Miller. “This is legal unless a state makes it illegal to send an abortifacient across state lines,” he added.
Many medications used in rheumatic diseases are harmful in pregnancy, and it’s important to routinely discuss pregnancy risk and planning in the rheumatology clinic, said Dr. Young. This should include a thorough discussion and referral for long-acting reversible contraception in most cases, she suggested.
Actions at the federal, state level
President Joe Biden recently signed an executive order prompting federal regulators to protect access to medication abortions, among other steps to safeguard access to reproductive services.
In a statement on Twitter, the American College of Rheumatology (ACR) said that it was “ ... following this issue closely to determine if rheumatology providers and patients are experiencing any widespread difficulty accessing methotrexate or if any initial disruptions are potentially temporary and due to the independent actions of pharmacists trying to figure out what is and isn’t allowed where they practice.”
ACR has assembled a task force of medical and policy experts to determine the best course of action for patients.
The Arthritis Foundation also continues to monitor the situation, encouraging patients to call its hotline, said Steven Schultz, director of state legislative affairs, in an interview.
“We are analyzing how medication abortion could cause confusion on the part of providers or pharmacists dispensing the medication and what this means for specific patients,” said Mr. Schultz. Through a survey, the foundation hopes to get a better idea of what’s going on in the states at a macro level.
This may take some time, as states go through a process of lawsuits, injunctions, or coming into session to do something that may affect access to MTX, said Mr. Schultz.
Being involved in local advocacy is more important than ever, stressed Dr. Young. “Additionally, being plugged into what the ACR and other advocacy groups are doing on the national level is helpful as well to know the status of these medication access issues.”
Rheumatologists have a unique voice in this discussion, she added. “We guide our patients to stability for a safe pregnancy, and even with careful planning, we see patients who become critically ill during pregnancy and require lifesaving treatment, which at times can mean an abortion is necessary.”
Oncologists also advocate for their patients on a regular basis to make sure they have access to the care they need, said Dr. Westin. This situation with Roe is no different, he added. “We will continue to use our unique expertise to advocate for policies that assure access to high-quality, evidence-based care – and to help our patients overcome barriers that may interfere.”
Dr. Reveille participated on an advisory board with Eli Lilly in October 2021.
A version of this article first appeared on Medscape.com.
.
The Court’s 5-4 decision in Dobbs v. Jackson Women’s Health Organization, which halted abortion procedures across the country, also appears to be affecting certain drug regimens. Reports have emerged that pharmacies are denying access to methotrexate (MTX), a drug often used in patients with arthritis or cancer, as well as psoriasis and other skin diseases. In very high doses, MTX it is used to terminate an ectopic pregnancy after miscarriage. The drug can also lead to birth defects.
“It’s happening all over,” Donald Miller, PharmD, professor of pharmacy practice at North Dakota State University, Fargo, said in an interview. “Pharmacists are reluctant to dispense it, and rheumatologists are reluctant to prescribe it because they’re afraid of going to jail.”
Becky Schwartz, a patient who takes MTX for lupus, recently tweeted that her physician’s office stopped prescribing the drug because it is considered an abortifacient. “I had care that made my disabled life easier, and [the Supreme Court] took that from me,” Ms. Schwartz wrote.
Prior to the Supreme Court’s ruling, physicians were concerned about the impact an overturning of the 1973 law would have on patient access to MTX and other prescription medications with abortifacient properties. Doctors in general are becoming afraid of prescribing anything that’s a teratogen, said Dr. Miller.
MTX is used far more often for autoimmune disease than as an abortifacient, said rheumatologist Kristen Young, MD, clinical assistant professor at the University of Arizona College of Medicine, Phoenix. It’s a slippery slope if states reacting to the Supreme Court ruling start regulating oral abortifacients, she added. Specifically, this will have a significant impact on patients with rheumatic disease.
Texas pharmacies target two drugs
MTX denials have caught the attention of health care organizations. “Uncertainty in financial and criminal liability for health care professionals in certain state laws and regulations are possibly compromising continuity of care and access [to] medications proven to be safe and effective by the Food and Drug Administration for these indications,” warned the American Pharmacists Association (APhA) in a statement to this news organization.
The APhA said that it was monitoring this situation to assess the effect on patients and pharmacists.
The Arthritis Foundation was made aware of challenges from patients in accessing their MTX prescription for managing their arthritis and shared a statement on the Foundation’s website.
In Texas, pharmacists can refuse to fill scripts for misoprostol and MTX, a combination used for medical abortions. According to the foundation, “Already there are reports that people in Texas who miscarry or take methotrexate for arthritis [are] having trouble getting their prescriptions filled.”
MTX, approved by the FDA in 1985, “is the absolute cornerstone of rheumatoid arthritis. We cannot deny our patients this incredibly valuable drug,” said John Reveille, MD, vice-chair for the department of medicine at the University of Texas McGovern School of Medicine and a member of the Arthritis Foundation expert panel, in an interview.
“While it’s true that methotrexate can be lethal to the fetus, misoprostol is much more likely to cause a spontaneous abortion, and the combination is especially effective,” he said.
“If you look at Cochrane clinical studies, the dose of misoprostol contained in certain combinations with NSAIDs [nonsteroidal anti-inflammatory drugs] can induce spontaneous abortions. It’s surprising that pharmacists are targeting methotrexate, an essential drug in arthritis treatment, when there are medications available that do not have this benefit that can by themselves cause loss of the fetus, such as mifepristone,” added Dr. Reveille.
The Dobbs ruling could also affect the ability of oncologists to provide lifesaving cancer care, according to Jason Westin, MD, an oncologist at the University of Texas MD Anderson Cancer Center in the department of lymphoma and myeloma.
“We have heard of medications with multiple indications, such as methotrexate, not being dispensed by pharmacies due to confusion regarding the intended use and potential consequences for the health care team,” he said in an interview.
Conflicting laws pose challenges for physicians
In North Dakota, inconsistencies in several laws are making it difficult for physicians and pharmacists to make decisions. “Lots of confusion can result when people pass laws against abortion. There’s sometimes no insight into the ramifications of those laws,” said Dr. Miller.
North Dakota approved a trigger law several years ago that makes abortion illegal 30 days after an overturning of Roe. However, another law that regulates abortion conflicts with the trigger law. “Some of the language will need clarification in the next legislative session,” he said.
APhA and other pharmacy associations strongly favor not interfering with the doctor- or pharmacist-patient relationship. The law needs to defer to appropriate care between doctor and patient, said Dr. Miller. State pharmacy associations in North Dakota are working with legislatures to clarify any exceptions in the law, he added.
Arizona lawmakers are trying to reconcile two abortion laws on the books. One, based on an 1864 territorial law, deems abortion illegal. In addition, a newly approved law bans abortions after 15 weeks. The latter will go into effect in September 2022. In both laws, a risk to the mother’s life is the only exception for abortion, said Dr. Young.
Denials aren’t widespread
Not all doctors are seeing MTX denials, but they’re worried about the future. “To date, we have not encountered difficulty in obtaining methotrexate based upon state abortion restrictions but are concerned that this could occur and result in dangerous delays in care,” said Dr. Westin.
Dr. Reveille, who practices rheumatology in Houston, has not yet received any complaints from patients. Things may be different in more rural parts of Texas, where pharmacists could be denying prescriptions based on religious issues, he offered.
It’s a little soon to see what repercussions may result from the Supreme Court ruling and state actions, said Dr. Reveille. “In Texas, we’re a bit ahead of the tidal wave.”
Access problems also haven’t shown up at the university clinic where Dr. Young practices. “In Arizona, it’s unclear if there would be a legal basis to refuse a person methotrexate on the basis that it can be used as an abortifacient,” she said.
Specificity is key in writing Rx scripts
Physicians can make things easier for patients by writing the indication and dose for the drug on the prescription slip. For example, a 10-mg script for MTX is not going to be used for an abortion, said Dr. Miller.
Rheumatologists in Texas have been doing this for some time, even before the Supreme Court ruling, said Fehmida Zahabi, MD, FACR, president of the Society of Texas Association of Rheumatology. For MTX prescriptions in premenopausal women, “patients are told their doctor needs to call the pharmacist. In the small print, we are asked to give a diagnosis to make sure we aren’t using it to terminate pregnancies,” said Dr. Zahabi.
She further noted that if the diagnosis is already indicated on the script, pharmacies generally won’t give patients a hard time.
Patients can also ask their physicians for a letter of medical necessity that confirms a drug’s use for a specific medical condition.
Mail order is another option if a local pharmacy won’t fill a prescription, said Dr. Miller. “This is legal unless a state makes it illegal to send an abortifacient across state lines,” he added.
Many medications used in rheumatic diseases are harmful in pregnancy, and it’s important to routinely discuss pregnancy risk and planning in the rheumatology clinic, said Dr. Young. This should include a thorough discussion and referral for long-acting reversible contraception in most cases, she suggested.
Actions at the federal, state level
President Joe Biden recently signed an executive order prompting federal regulators to protect access to medication abortions, among other steps to safeguard access to reproductive services.
In a statement on Twitter, the American College of Rheumatology (ACR) said that it was “ ... following this issue closely to determine if rheumatology providers and patients are experiencing any widespread difficulty accessing methotrexate or if any initial disruptions are potentially temporary and due to the independent actions of pharmacists trying to figure out what is and isn’t allowed where they practice.”
ACR has assembled a task force of medical and policy experts to determine the best course of action for patients.
The Arthritis Foundation also continues to monitor the situation, encouraging patients to call its hotline, said Steven Schultz, director of state legislative affairs, in an interview.
“We are analyzing how medication abortion could cause confusion on the part of providers or pharmacists dispensing the medication and what this means for specific patients,” said Mr. Schultz. Through a survey, the foundation hopes to get a better idea of what’s going on in the states at a macro level.
This may take some time, as states go through a process of lawsuits, injunctions, or coming into session to do something that may affect access to MTX, said Mr. Schultz.
Being involved in local advocacy is more important than ever, stressed Dr. Young. “Additionally, being plugged into what the ACR and other advocacy groups are doing on the national level is helpful as well to know the status of these medication access issues.”
Rheumatologists have a unique voice in this discussion, she added. “We guide our patients to stability for a safe pregnancy, and even with careful planning, we see patients who become critically ill during pregnancy and require lifesaving treatment, which at times can mean an abortion is necessary.”
Oncologists also advocate for their patients on a regular basis to make sure they have access to the care they need, said Dr. Westin. This situation with Roe is no different, he added. “We will continue to use our unique expertise to advocate for policies that assure access to high-quality, evidence-based care – and to help our patients overcome barriers that may interfere.”
Dr. Reveille participated on an advisory board with Eli Lilly in October 2021.
A version of this article first appeared on Medscape.com.
.
The Court’s 5-4 decision in Dobbs v. Jackson Women’s Health Organization, which halted abortion procedures across the country, also appears to be affecting certain drug regimens. Reports have emerged that pharmacies are denying access to methotrexate (MTX), a drug often used in patients with arthritis or cancer, as well as psoriasis and other skin diseases. In very high doses, MTX it is used to terminate an ectopic pregnancy after miscarriage. The drug can also lead to birth defects.
“It’s happening all over,” Donald Miller, PharmD, professor of pharmacy practice at North Dakota State University, Fargo, said in an interview. “Pharmacists are reluctant to dispense it, and rheumatologists are reluctant to prescribe it because they’re afraid of going to jail.”
Becky Schwartz, a patient who takes MTX for lupus, recently tweeted that her physician’s office stopped prescribing the drug because it is considered an abortifacient. “I had care that made my disabled life easier, and [the Supreme Court] took that from me,” Ms. Schwartz wrote.
Prior to the Supreme Court’s ruling, physicians were concerned about the impact an overturning of the 1973 law would have on patient access to MTX and other prescription medications with abortifacient properties. Doctors in general are becoming afraid of prescribing anything that’s a teratogen, said Dr. Miller.
MTX is used far more often for autoimmune disease than as an abortifacient, said rheumatologist Kristen Young, MD, clinical assistant professor at the University of Arizona College of Medicine, Phoenix. It’s a slippery slope if states reacting to the Supreme Court ruling start regulating oral abortifacients, she added. Specifically, this will have a significant impact on patients with rheumatic disease.
Texas pharmacies target two drugs
MTX denials have caught the attention of health care organizations. “Uncertainty in financial and criminal liability for health care professionals in certain state laws and regulations are possibly compromising continuity of care and access [to] medications proven to be safe and effective by the Food and Drug Administration for these indications,” warned the American Pharmacists Association (APhA) in a statement to this news organization.
The APhA said that it was monitoring this situation to assess the effect on patients and pharmacists.
The Arthritis Foundation was made aware of challenges from patients in accessing their MTX prescription for managing their arthritis and shared a statement on the Foundation’s website.
In Texas, pharmacists can refuse to fill scripts for misoprostol and MTX, a combination used for medical abortions. According to the foundation, “Already there are reports that people in Texas who miscarry or take methotrexate for arthritis [are] having trouble getting their prescriptions filled.”
MTX, approved by the FDA in 1985, “is the absolute cornerstone of rheumatoid arthritis. We cannot deny our patients this incredibly valuable drug,” said John Reveille, MD, vice-chair for the department of medicine at the University of Texas McGovern School of Medicine and a member of the Arthritis Foundation expert panel, in an interview.
“While it’s true that methotrexate can be lethal to the fetus, misoprostol is much more likely to cause a spontaneous abortion, and the combination is especially effective,” he said.
“If you look at Cochrane clinical studies, the dose of misoprostol contained in certain combinations with NSAIDs [nonsteroidal anti-inflammatory drugs] can induce spontaneous abortions. It’s surprising that pharmacists are targeting methotrexate, an essential drug in arthritis treatment, when there are medications available that do not have this benefit that can by themselves cause loss of the fetus, such as mifepristone,” added Dr. Reveille.
The Dobbs ruling could also affect the ability of oncologists to provide lifesaving cancer care, according to Jason Westin, MD, an oncologist at the University of Texas MD Anderson Cancer Center in the department of lymphoma and myeloma.
“We have heard of medications with multiple indications, such as methotrexate, not being dispensed by pharmacies due to confusion regarding the intended use and potential consequences for the health care team,” he said in an interview.
Conflicting laws pose challenges for physicians
In North Dakota, inconsistencies in several laws are making it difficult for physicians and pharmacists to make decisions. “Lots of confusion can result when people pass laws against abortion. There’s sometimes no insight into the ramifications of those laws,” said Dr. Miller.
North Dakota approved a trigger law several years ago that makes abortion illegal 30 days after an overturning of Roe. However, another law that regulates abortion conflicts with the trigger law. “Some of the language will need clarification in the next legislative session,” he said.
APhA and other pharmacy associations strongly favor not interfering with the doctor- or pharmacist-patient relationship. The law needs to defer to appropriate care between doctor and patient, said Dr. Miller. State pharmacy associations in North Dakota are working with legislatures to clarify any exceptions in the law, he added.
Arizona lawmakers are trying to reconcile two abortion laws on the books. One, based on an 1864 territorial law, deems abortion illegal. In addition, a newly approved law bans abortions after 15 weeks. The latter will go into effect in September 2022. In both laws, a risk to the mother’s life is the only exception for abortion, said Dr. Young.
Denials aren’t widespread
Not all doctors are seeing MTX denials, but they’re worried about the future. “To date, we have not encountered difficulty in obtaining methotrexate based upon state abortion restrictions but are concerned that this could occur and result in dangerous delays in care,” said Dr. Westin.
Dr. Reveille, who practices rheumatology in Houston, has not yet received any complaints from patients. Things may be different in more rural parts of Texas, where pharmacists could be denying prescriptions based on religious issues, he offered.
It’s a little soon to see what repercussions may result from the Supreme Court ruling and state actions, said Dr. Reveille. “In Texas, we’re a bit ahead of the tidal wave.”
Access problems also haven’t shown up at the university clinic where Dr. Young practices. “In Arizona, it’s unclear if there would be a legal basis to refuse a person methotrexate on the basis that it can be used as an abortifacient,” she said.
Specificity is key in writing Rx scripts
Physicians can make things easier for patients by writing the indication and dose for the drug on the prescription slip. For example, a 10-mg script for MTX is not going to be used for an abortion, said Dr. Miller.
Rheumatologists in Texas have been doing this for some time, even before the Supreme Court ruling, said Fehmida Zahabi, MD, FACR, president of the Society of Texas Association of Rheumatology. For MTX prescriptions in premenopausal women, “patients are told their doctor needs to call the pharmacist. In the small print, we are asked to give a diagnosis to make sure we aren’t using it to terminate pregnancies,” said Dr. Zahabi.
She further noted that if the diagnosis is already indicated on the script, pharmacies generally won’t give patients a hard time.
Patients can also ask their physicians for a letter of medical necessity that confirms a drug’s use for a specific medical condition.
Mail order is another option if a local pharmacy won’t fill a prescription, said Dr. Miller. “This is legal unless a state makes it illegal to send an abortifacient across state lines,” he added.
Many medications used in rheumatic diseases are harmful in pregnancy, and it’s important to routinely discuss pregnancy risk and planning in the rheumatology clinic, said Dr. Young. This should include a thorough discussion and referral for long-acting reversible contraception in most cases, she suggested.
Actions at the federal, state level
President Joe Biden recently signed an executive order prompting federal regulators to protect access to medication abortions, among other steps to safeguard access to reproductive services.
In a statement on Twitter, the American College of Rheumatology (ACR) said that it was “ ... following this issue closely to determine if rheumatology providers and patients are experiencing any widespread difficulty accessing methotrexate or if any initial disruptions are potentially temporary and due to the independent actions of pharmacists trying to figure out what is and isn’t allowed where they practice.”
ACR has assembled a task force of medical and policy experts to determine the best course of action for patients.
The Arthritis Foundation also continues to monitor the situation, encouraging patients to call its hotline, said Steven Schultz, director of state legislative affairs, in an interview.
“We are analyzing how medication abortion could cause confusion on the part of providers or pharmacists dispensing the medication and what this means for specific patients,” said Mr. Schultz. Through a survey, the foundation hopes to get a better idea of what’s going on in the states at a macro level.
This may take some time, as states go through a process of lawsuits, injunctions, or coming into session to do something that may affect access to MTX, said Mr. Schultz.
Being involved in local advocacy is more important than ever, stressed Dr. Young. “Additionally, being plugged into what the ACR and other advocacy groups are doing on the national level is helpful as well to know the status of these medication access issues.”
Rheumatologists have a unique voice in this discussion, she added. “We guide our patients to stability for a safe pregnancy, and even with careful planning, we see patients who become critically ill during pregnancy and require lifesaving treatment, which at times can mean an abortion is necessary.”
Oncologists also advocate for their patients on a regular basis to make sure they have access to the care they need, said Dr. Westin. This situation with Roe is no different, he added. “We will continue to use our unique expertise to advocate for policies that assure access to high-quality, evidence-based care – and to help our patients overcome barriers that may interfere.”
Dr. Reveille participated on an advisory board with Eli Lilly in October 2021.
A version of this article first appeared on Medscape.com.
Pregnancy, breastfeeding, and more linked to lower CRC risk
Estrogen exposure helps protect against colorectal cancer (CRC), and in some instances, the protection is site specific, a new analysis finds.
In a 17-year study involving almost 5,000 women, researchers from Germany found that hormone replacement therapy, oral contraceptive use, pregnancy, breastfeeding, and menopause at age 50 or older were all significantly associated with reductions in CRC risk.
Interestingly, the reduced risk of CRC observed for pregnancy and breastfeeding only applied to proximal colon cancer, while the association with oral contraceptive use was confined to the distal colon and rectum.
The results were published online in JNCI Cancer Spectrum.
CRC is the second most common cause of cancer death. It is responsible for more than one million deaths globally, according to the latest figures from the Global Burden of Disease 2019 Cancer Collaboration.
And sex seems to make a difference. The Global Burden analysis, echoing previous data, found that CRC is less common among women and that fewer women die from the disease.
Little, however, is known about the mechanisms of estrogen signaling in CRC or the impact of reproductive factors on CRC, despite a large amount of literature linking CRC risk to exogenous estrogens, such as hormone replacement therapy and oral contraceptives.
In the current analysis, the team recruited 2,650 patients with CRC from 20 German cancer centers between 2003 and 2020. Researchers used standardized questionnaires to garner the women’s reproductive histories.
A matched control group of 2,175 participants who did not have a history of CRC was randomly selected from population registries. All analyses were adjusted for known CRC risk factors, such as age; body mass index; education level; family history; having previously undergone large-bowel endoscopy; diabetes; and smoking status.
The researchers found that each pregnancy was associated with a small but significant 9% reduction in CRC risk (odds ratio, 0.91), specifically in the proximal colon (OR, 0.86).
Overall, breastfeeding for a year or longer was associated with a significantly lower CRC risk, compared with never breastfeeding (OR, 0.74), but the results were only significant for the proximal colon (OR, 0.58).
Oral contraceptive use for 9 years or longer was associated with a lower CRC risk (OR, 0.75) but was only significant for the distal colon (OR, 0.63). Hormone replacement therapy was associated with a lower risk of CRC irrespective of tumor location (OR, 0.76). And using both was linked to a 42% CRC risk reduction (OR, 0.58).
Although age at menarche was not associated with CRC risk, menopause at age 50 or older was associated with a significant 17% lower risk of CRC.
In an email interview, lead author Tobias Niedermaier, PhD, expressed surprise at two of the findings. The first was the small association between pregnancies and CRC risk, “despite the strong increase in estrogen levels during pregnancy,” he said. He speculated that pregnancy-related increases in insulin levels may have “largely offset the protection effects of estrogen exposure during pregnancy.”
The second surprise was that the age at menarche did not have a bearing on CRC risk, which could be because “exposure to estrogen levels in younger ages [is] less relevant with respect to CRC risk, because CRC typically develops at comparably old age.”
John Marshall, MD, who was not involved in the research, commented that such studies “put a lot of pressure on people to perform in a certain way to modify their personal risk of something.” However, “we would not recommend people alter their life choices for reproduction for this,” said Dr. Marshall, chief of the Division of Hematology/Oncology at Georgetown University, Washington, D.C.
Dr. Niedermaier agreed that “while this knowledge will certainly not change a woman’s decision on family planning,” he noted that the findings “could influence current CRC screening strategies, for example, by risk-adapted screening intervals [and] start and stop ages of screening.”
Dr. Niedermaier and colleagues’ work was funded by the German Research Council, the German Federal Ministry of Education and Research, and the Interdisciplinary Research Program of the National Center for Tumor Diseases. Dr. Niedermaier has disclosed no relevant financial relationships. Dr. Marshall writes a column that appears regularly on Medscape: Marshall on Oncology. He has served as speaker or member of a speakers’ bureau for Genentech, Amgen, Bayer, Celgene Corporation, and Caris Life Sciences.
A version of this article first appeared on Medscape.com.
Estrogen exposure helps protect against colorectal cancer (CRC), and in some instances, the protection is site specific, a new analysis finds.
In a 17-year study involving almost 5,000 women, researchers from Germany found that hormone replacement therapy, oral contraceptive use, pregnancy, breastfeeding, and menopause at age 50 or older were all significantly associated with reductions in CRC risk.
Interestingly, the reduced risk of CRC observed for pregnancy and breastfeeding only applied to proximal colon cancer, while the association with oral contraceptive use was confined to the distal colon and rectum.
The results were published online in JNCI Cancer Spectrum.
CRC is the second most common cause of cancer death. It is responsible for more than one million deaths globally, according to the latest figures from the Global Burden of Disease 2019 Cancer Collaboration.
And sex seems to make a difference. The Global Burden analysis, echoing previous data, found that CRC is less common among women and that fewer women die from the disease.
Little, however, is known about the mechanisms of estrogen signaling in CRC or the impact of reproductive factors on CRC, despite a large amount of literature linking CRC risk to exogenous estrogens, such as hormone replacement therapy and oral contraceptives.
In the current analysis, the team recruited 2,650 patients with CRC from 20 German cancer centers between 2003 and 2020. Researchers used standardized questionnaires to garner the women’s reproductive histories.
A matched control group of 2,175 participants who did not have a history of CRC was randomly selected from population registries. All analyses were adjusted for known CRC risk factors, such as age; body mass index; education level; family history; having previously undergone large-bowel endoscopy; diabetes; and smoking status.
The researchers found that each pregnancy was associated with a small but significant 9% reduction in CRC risk (odds ratio, 0.91), specifically in the proximal colon (OR, 0.86).
Overall, breastfeeding for a year or longer was associated with a significantly lower CRC risk, compared with never breastfeeding (OR, 0.74), but the results were only significant for the proximal colon (OR, 0.58).
Oral contraceptive use for 9 years or longer was associated with a lower CRC risk (OR, 0.75) but was only significant for the distal colon (OR, 0.63). Hormone replacement therapy was associated with a lower risk of CRC irrespective of tumor location (OR, 0.76). And using both was linked to a 42% CRC risk reduction (OR, 0.58).
Although age at menarche was not associated with CRC risk, menopause at age 50 or older was associated with a significant 17% lower risk of CRC.
In an email interview, lead author Tobias Niedermaier, PhD, expressed surprise at two of the findings. The first was the small association between pregnancies and CRC risk, “despite the strong increase in estrogen levels during pregnancy,” he said. He speculated that pregnancy-related increases in insulin levels may have “largely offset the protection effects of estrogen exposure during pregnancy.”
The second surprise was that the age at menarche did not have a bearing on CRC risk, which could be because “exposure to estrogen levels in younger ages [is] less relevant with respect to CRC risk, because CRC typically develops at comparably old age.”
John Marshall, MD, who was not involved in the research, commented that such studies “put a lot of pressure on people to perform in a certain way to modify their personal risk of something.” However, “we would not recommend people alter their life choices for reproduction for this,” said Dr. Marshall, chief of the Division of Hematology/Oncology at Georgetown University, Washington, D.C.
Dr. Niedermaier agreed that “while this knowledge will certainly not change a woman’s decision on family planning,” he noted that the findings “could influence current CRC screening strategies, for example, by risk-adapted screening intervals [and] start and stop ages of screening.”
Dr. Niedermaier and colleagues’ work was funded by the German Research Council, the German Federal Ministry of Education and Research, and the Interdisciplinary Research Program of the National Center for Tumor Diseases. Dr. Niedermaier has disclosed no relevant financial relationships. Dr. Marshall writes a column that appears regularly on Medscape: Marshall on Oncology. He has served as speaker or member of a speakers’ bureau for Genentech, Amgen, Bayer, Celgene Corporation, and Caris Life Sciences.
A version of this article first appeared on Medscape.com.
Estrogen exposure helps protect against colorectal cancer (CRC), and in some instances, the protection is site specific, a new analysis finds.
In a 17-year study involving almost 5,000 women, researchers from Germany found that hormone replacement therapy, oral contraceptive use, pregnancy, breastfeeding, and menopause at age 50 or older were all significantly associated with reductions in CRC risk.
Interestingly, the reduced risk of CRC observed for pregnancy and breastfeeding only applied to proximal colon cancer, while the association with oral contraceptive use was confined to the distal colon and rectum.
The results were published online in JNCI Cancer Spectrum.
CRC is the second most common cause of cancer death. It is responsible for more than one million deaths globally, according to the latest figures from the Global Burden of Disease 2019 Cancer Collaboration.
And sex seems to make a difference. The Global Burden analysis, echoing previous data, found that CRC is less common among women and that fewer women die from the disease.
Little, however, is known about the mechanisms of estrogen signaling in CRC or the impact of reproductive factors on CRC, despite a large amount of literature linking CRC risk to exogenous estrogens, such as hormone replacement therapy and oral contraceptives.
In the current analysis, the team recruited 2,650 patients with CRC from 20 German cancer centers between 2003 and 2020. Researchers used standardized questionnaires to garner the women’s reproductive histories.
A matched control group of 2,175 participants who did not have a history of CRC was randomly selected from population registries. All analyses were adjusted for known CRC risk factors, such as age; body mass index; education level; family history; having previously undergone large-bowel endoscopy; diabetes; and smoking status.
The researchers found that each pregnancy was associated with a small but significant 9% reduction in CRC risk (odds ratio, 0.91), specifically in the proximal colon (OR, 0.86).
Overall, breastfeeding for a year or longer was associated with a significantly lower CRC risk, compared with never breastfeeding (OR, 0.74), but the results were only significant for the proximal colon (OR, 0.58).
Oral contraceptive use for 9 years or longer was associated with a lower CRC risk (OR, 0.75) but was only significant for the distal colon (OR, 0.63). Hormone replacement therapy was associated with a lower risk of CRC irrespective of tumor location (OR, 0.76). And using both was linked to a 42% CRC risk reduction (OR, 0.58).
Although age at menarche was not associated with CRC risk, menopause at age 50 or older was associated with a significant 17% lower risk of CRC.
In an email interview, lead author Tobias Niedermaier, PhD, expressed surprise at two of the findings. The first was the small association between pregnancies and CRC risk, “despite the strong increase in estrogen levels during pregnancy,” he said. He speculated that pregnancy-related increases in insulin levels may have “largely offset the protection effects of estrogen exposure during pregnancy.”
The second surprise was that the age at menarche did not have a bearing on CRC risk, which could be because “exposure to estrogen levels in younger ages [is] less relevant with respect to CRC risk, because CRC typically develops at comparably old age.”
John Marshall, MD, who was not involved in the research, commented that such studies “put a lot of pressure on people to perform in a certain way to modify their personal risk of something.” However, “we would not recommend people alter their life choices for reproduction for this,” said Dr. Marshall, chief of the Division of Hematology/Oncology at Georgetown University, Washington, D.C.
Dr. Niedermaier agreed that “while this knowledge will certainly not change a woman’s decision on family planning,” he noted that the findings “could influence current CRC screening strategies, for example, by risk-adapted screening intervals [and] start and stop ages of screening.”
Dr. Niedermaier and colleagues’ work was funded by the German Research Council, the German Federal Ministry of Education and Research, and the Interdisciplinary Research Program of the National Center for Tumor Diseases. Dr. Niedermaier has disclosed no relevant financial relationships. Dr. Marshall writes a column that appears regularly on Medscape: Marshall on Oncology. He has served as speaker or member of a speakers’ bureau for Genentech, Amgen, Bayer, Celgene Corporation, and Caris Life Sciences.
A version of this article first appeared on Medscape.com.
Addressing posttraumatic stress disorder in children and adolescents
Luke is a 12-year-old who presents for a well-child visit accompanied by his foster mother. He appears more solemn and taciturn than at previous visits. He is not interested in talking about any topics, including things he enjoys. His foster mother states that he has been more irritable, oppositional, and behaviorally dysregulated over the past 2 months. She also notes that his sleep has been poor. He reports this is because of nightmares and trouble falling asleep. Luke states that he will at times remember seeing his mother being struck by his father and – even when he does not want to – will have thoughts about hiding from his dad after being hit. You learn from the foster mother that he has been residing with her for the past 2 months and that he is now in state custody following significant parental home substance use, witnessing domestic violence, and being physically abused by his father.
The above narrative may sound all too familiar to those in pediatric primary care. You may wonder if there is a potential posttraumatic response to the witnessed trauma, but does the patient meet criteria for a trauma-related disorder? If so, what are the best next steps?
Prevalence of posttraumatic stress disorder in the general pediatric population
According to the 2020 National Survey of Children’s Health, approximately 40% of children age 17 and under report experiencing at least one adverse childhood experience. Within the 12-17 age range, it rises to over 50%.1 Adverse childhood experiences (ACEs) are potentially traumatic events and include items such as experiencing violence/abuse/neglect, witnessing violence in the home or community, having a family member attempt or die by suicide, and other adverse household and environmental situations. The accumulation of these ACEs can lead to long-term adverse emotional, physical, and behavioral outcomes.2
However, adverse childhood experiences do not always translate into PTSD. According to one national survey of 13- to 18-year-olds, the lifetime prevalence of PTSD is notably lower than exposure rates to ACEs and is estimated at 5% of adolescents, with higher rates among females (8%) versus males (2.3%).3
There are various risk factors for the development of PTSD that may play a role including genetic vulnerability, length of the trauma (for example, a one-time event versus repeated trauma for years), characteristics specific to the trauma, and the aftermath of the trauma. Again, it is important to note that not all youth exposed to a traumatic event will develop PTSD. Those who do make up a small percentage of at-risk children.4
Diagnosing PTSD in a child or adolescent
For a pediatric patient to be diagnosed with PTSD according to the DSM-5 criteria, they must experience a potentially traumatic event and meet criteria from four categories of symptoms. Trauma is defined as direct or indirect exposure to actual or threatened death, serious injury, or sexual violence. The four symptom categories are re-experiencing, avoidance, hyperarousal, and negative alteration in cognition and mood. The number of symptoms needed from each category varies based on the child’s age, with differing cutoffs based on whether the child is younger or older than 6 years old. Moreover, symptoms must be present for at least 1 month.5
Trauma can be assessed in the office by using a focused interview that includes the full DSM diagnostic criteria. There are additional trauma rating screeners and assessment tools that can be used including the Child PTSD Symptom Scale, Child Trauma Screening Questionnaire, UCLA Posttraumatic Stress Disorder Reaction Index, and the Trauma Symptom Checklist for Children, to name a few. Many of these allow for multiple informants, including the child/adolescent, thereby allowing for varying perspectives regarding trauma reactions.
Treatment options
Familiarity with evidence-based treatment for trauma may be useful to ensure that referral is targeted for the patient/family. There are no Food and Drug Administrations–approved medications for children with PTSD, though medications can be used to target specific PTSD symptoms (e.g. prazosin for trauma-related nightmares) as well as commonly comorbid conditions such as depression. Becoming familiar with the available therapeutic modalities offered in your area is recommended.
Highlighting trauma-focused cognitive behavioral therapy (TF-CBT)
The treatment with the most research evidence for traumatized children is trauma-focused cognitive behavioral therapy (TF-CBT), which is a 12- to 25-session therapeutic intervention for patients 3-18 years old (with some evidence for young adults as well) with PTSD and/or trauma-related behaviors. TF-CBT uses a components-based treatment model encompassed by the PRACTICE acronym/mnemonic.6,7
- P – Psychoeducation and parenting skills.
- R – Relaxation techniques: Focused breathing, progressive muscle relaxation, and teaching the child to control their thoughts (thought stopping).
- A – Affective expression and regulation (feeling identification): To help the child and parent learn to control their emotional reaction to reminders by expanding their emotional vocabulary, enhancing their skills in identification and expression of emotions, and encouraging self-soothing activities
- C – Cognitive coping and processing: Through this component, the child learns to understand the relationships between thoughts, feelings, and behaviors and think in new and healthier ways.
- T – Trauma narrative and processing: Gradual exposure exercises including verbal, written, and/or symbolic recounting of traumatic event(s) so the child learns to be able to discuss the events when they choose to in ways that do not produce overwhelming emotions. Following the completion of the narrative, clients are supported in identifying, challenging, and correcting cognitive distortions and dysfunctional beliefs.
- I – In vivo exposure: Encourage the gradual exposure to innocuous trauma reminders in the child’s environment so the child learns they can control their emotional reactions to things that remind them of the trauma, starting with nonthreatening examples of reminders.
- C – Conjoint parent/child sessions: Sessions generally deal with psycho-education, sharing the trauma narrative, anxiety management, and correction of cognitive distortions. The family works to enhance communication and create opportunities for therapeutic discussion regarding the trauma.
- E – Enhancing personal safety and future growth: Provide training and education with respect to personal safety skills and healthy sexuality and interpersonal relationships; encourage the utilization of skills learned in managing future stressors and/or trauma reminders.
Of note, some elements of this therapy that could possibly be easily incorporated into a primary care office visit include relaxation techniques and focus on coping skills/strategies.
Summary
Children and adolescents often present with trauma-related symptoms to the primary care office. Having increasing familiarity with PTSD diagnostic criteria and treatment modalities will likely lead to increased confidence and comfort recognizing symptoms and when placing a referral. This may also lead to shorter wait times for receiving targeted treatment and ultimately should lead to better outcomes for affected children and families.
Dr. Abdul-Kareem is at the University of Vermont, Burlington.
References
1. National Survey of Children’s Health (2016 - present). https://nschdata.org/browse/survey.
2. Adverse Childhood Experiences (ACEs). Centers for Disease Control and Prevention. https://www.cdc.gov/violenceprevention/aces/index.html].
3. Post-Traumatic Stress Disorder (PTSD). National Institute of Mental Health. https://www.nimh.nih.gov/health/statistics/post-traumatic-stress-disorder-ptsd,
4. Martin A et al. Lewis’s Child and Adolescent Psychiatry (5th edition). Lippincott Williams & Wilkins: Philadelphia, 2017.
5. American Psychiatric Association. Neurodevelopmental disorders. In: DSM-5. 2013.
6. Trauma-Focused Cognitive Behavioral Therapy. The National Child Traumatic Stress Network. https://www.nctsn.org/interventions/trauma-focused-cognitive-behavioral-therapy.
7. Trauma-Focused Cognitive-Behavioral Therapy (TF-CBT). California Evidence-Based Clearinghouse for Child Welfare. https://www.cebc4cw.org/program/trauma-focused-cognitive-behavioral-therapy/.
Luke is a 12-year-old who presents for a well-child visit accompanied by his foster mother. He appears more solemn and taciturn than at previous visits. He is not interested in talking about any topics, including things he enjoys. His foster mother states that he has been more irritable, oppositional, and behaviorally dysregulated over the past 2 months. She also notes that his sleep has been poor. He reports this is because of nightmares and trouble falling asleep. Luke states that he will at times remember seeing his mother being struck by his father and – even when he does not want to – will have thoughts about hiding from his dad after being hit. You learn from the foster mother that he has been residing with her for the past 2 months and that he is now in state custody following significant parental home substance use, witnessing domestic violence, and being physically abused by his father.
The above narrative may sound all too familiar to those in pediatric primary care. You may wonder if there is a potential posttraumatic response to the witnessed trauma, but does the patient meet criteria for a trauma-related disorder? If so, what are the best next steps?
Prevalence of posttraumatic stress disorder in the general pediatric population
According to the 2020 National Survey of Children’s Health, approximately 40% of children age 17 and under report experiencing at least one adverse childhood experience. Within the 12-17 age range, it rises to over 50%.1 Adverse childhood experiences (ACEs) are potentially traumatic events and include items such as experiencing violence/abuse/neglect, witnessing violence in the home or community, having a family member attempt or die by suicide, and other adverse household and environmental situations. The accumulation of these ACEs can lead to long-term adverse emotional, physical, and behavioral outcomes.2
However, adverse childhood experiences do not always translate into PTSD. According to one national survey of 13- to 18-year-olds, the lifetime prevalence of PTSD is notably lower than exposure rates to ACEs and is estimated at 5% of adolescents, with higher rates among females (8%) versus males (2.3%).3
There are various risk factors for the development of PTSD that may play a role including genetic vulnerability, length of the trauma (for example, a one-time event versus repeated trauma for years), characteristics specific to the trauma, and the aftermath of the trauma. Again, it is important to note that not all youth exposed to a traumatic event will develop PTSD. Those who do make up a small percentage of at-risk children.4
Diagnosing PTSD in a child or adolescent
For a pediatric patient to be diagnosed with PTSD according to the DSM-5 criteria, they must experience a potentially traumatic event and meet criteria from four categories of symptoms. Trauma is defined as direct or indirect exposure to actual or threatened death, serious injury, or sexual violence. The four symptom categories are re-experiencing, avoidance, hyperarousal, and negative alteration in cognition and mood. The number of symptoms needed from each category varies based on the child’s age, with differing cutoffs based on whether the child is younger or older than 6 years old. Moreover, symptoms must be present for at least 1 month.5
Trauma can be assessed in the office by using a focused interview that includes the full DSM diagnostic criteria. There are additional trauma rating screeners and assessment tools that can be used including the Child PTSD Symptom Scale, Child Trauma Screening Questionnaire, UCLA Posttraumatic Stress Disorder Reaction Index, and the Trauma Symptom Checklist for Children, to name a few. Many of these allow for multiple informants, including the child/adolescent, thereby allowing for varying perspectives regarding trauma reactions.
Treatment options
Familiarity with evidence-based treatment for trauma may be useful to ensure that referral is targeted for the patient/family. There are no Food and Drug Administrations–approved medications for children with PTSD, though medications can be used to target specific PTSD symptoms (e.g. prazosin for trauma-related nightmares) as well as commonly comorbid conditions such as depression. Becoming familiar with the available therapeutic modalities offered in your area is recommended.
Highlighting trauma-focused cognitive behavioral therapy (TF-CBT)
The treatment with the most research evidence for traumatized children is trauma-focused cognitive behavioral therapy (TF-CBT), which is a 12- to 25-session therapeutic intervention for patients 3-18 years old (with some evidence for young adults as well) with PTSD and/or trauma-related behaviors. TF-CBT uses a components-based treatment model encompassed by the PRACTICE acronym/mnemonic.6,7
- P – Psychoeducation and parenting skills.
- R – Relaxation techniques: Focused breathing, progressive muscle relaxation, and teaching the child to control their thoughts (thought stopping).
- A – Affective expression and regulation (feeling identification): To help the child and parent learn to control their emotional reaction to reminders by expanding their emotional vocabulary, enhancing their skills in identification and expression of emotions, and encouraging self-soothing activities
- C – Cognitive coping and processing: Through this component, the child learns to understand the relationships between thoughts, feelings, and behaviors and think in new and healthier ways.
- T – Trauma narrative and processing: Gradual exposure exercises including verbal, written, and/or symbolic recounting of traumatic event(s) so the child learns to be able to discuss the events when they choose to in ways that do not produce overwhelming emotions. Following the completion of the narrative, clients are supported in identifying, challenging, and correcting cognitive distortions and dysfunctional beliefs.
- I – In vivo exposure: Encourage the gradual exposure to innocuous trauma reminders in the child’s environment so the child learns they can control their emotional reactions to things that remind them of the trauma, starting with nonthreatening examples of reminders.
- C – Conjoint parent/child sessions: Sessions generally deal with psycho-education, sharing the trauma narrative, anxiety management, and correction of cognitive distortions. The family works to enhance communication and create opportunities for therapeutic discussion regarding the trauma.
- E – Enhancing personal safety and future growth: Provide training and education with respect to personal safety skills and healthy sexuality and interpersonal relationships; encourage the utilization of skills learned in managing future stressors and/or trauma reminders.
Of note, some elements of this therapy that could possibly be easily incorporated into a primary care office visit include relaxation techniques and focus on coping skills/strategies.
Summary
Children and adolescents often present with trauma-related symptoms to the primary care office. Having increasing familiarity with PTSD diagnostic criteria and treatment modalities will likely lead to increased confidence and comfort recognizing symptoms and when placing a referral. This may also lead to shorter wait times for receiving targeted treatment and ultimately should lead to better outcomes for affected children and families.
Dr. Abdul-Kareem is at the University of Vermont, Burlington.
References
1. National Survey of Children’s Health (2016 - present). https://nschdata.org/browse/survey.
2. Adverse Childhood Experiences (ACEs). Centers for Disease Control and Prevention. https://www.cdc.gov/violenceprevention/aces/index.html].
3. Post-Traumatic Stress Disorder (PTSD). National Institute of Mental Health. https://www.nimh.nih.gov/health/statistics/post-traumatic-stress-disorder-ptsd,
4. Martin A et al. Lewis’s Child and Adolescent Psychiatry (5th edition). Lippincott Williams & Wilkins: Philadelphia, 2017.
5. American Psychiatric Association. Neurodevelopmental disorders. In: DSM-5. 2013.
6. Trauma-Focused Cognitive Behavioral Therapy. The National Child Traumatic Stress Network. https://www.nctsn.org/interventions/trauma-focused-cognitive-behavioral-therapy.
7. Trauma-Focused Cognitive-Behavioral Therapy (TF-CBT). California Evidence-Based Clearinghouse for Child Welfare. https://www.cebc4cw.org/program/trauma-focused-cognitive-behavioral-therapy/.
Luke is a 12-year-old who presents for a well-child visit accompanied by his foster mother. He appears more solemn and taciturn than at previous visits. He is not interested in talking about any topics, including things he enjoys. His foster mother states that he has been more irritable, oppositional, and behaviorally dysregulated over the past 2 months. She also notes that his sleep has been poor. He reports this is because of nightmares and trouble falling asleep. Luke states that he will at times remember seeing his mother being struck by his father and – even when he does not want to – will have thoughts about hiding from his dad after being hit. You learn from the foster mother that he has been residing with her for the past 2 months and that he is now in state custody following significant parental home substance use, witnessing domestic violence, and being physically abused by his father.
The above narrative may sound all too familiar to those in pediatric primary care. You may wonder if there is a potential posttraumatic response to the witnessed trauma, but does the patient meet criteria for a trauma-related disorder? If so, what are the best next steps?
Prevalence of posttraumatic stress disorder in the general pediatric population
According to the 2020 National Survey of Children’s Health, approximately 40% of children age 17 and under report experiencing at least one adverse childhood experience. Within the 12-17 age range, it rises to over 50%.1 Adverse childhood experiences (ACEs) are potentially traumatic events and include items such as experiencing violence/abuse/neglect, witnessing violence in the home or community, having a family member attempt or die by suicide, and other adverse household and environmental situations. The accumulation of these ACEs can lead to long-term adverse emotional, physical, and behavioral outcomes.2
However, adverse childhood experiences do not always translate into PTSD. According to one national survey of 13- to 18-year-olds, the lifetime prevalence of PTSD is notably lower than exposure rates to ACEs and is estimated at 5% of adolescents, with higher rates among females (8%) versus males (2.3%).3
There are various risk factors for the development of PTSD that may play a role including genetic vulnerability, length of the trauma (for example, a one-time event versus repeated trauma for years), characteristics specific to the trauma, and the aftermath of the trauma. Again, it is important to note that not all youth exposed to a traumatic event will develop PTSD. Those who do make up a small percentage of at-risk children.4
Diagnosing PTSD in a child or adolescent
For a pediatric patient to be diagnosed with PTSD according to the DSM-5 criteria, they must experience a potentially traumatic event and meet criteria from four categories of symptoms. Trauma is defined as direct or indirect exposure to actual or threatened death, serious injury, or sexual violence. The four symptom categories are re-experiencing, avoidance, hyperarousal, and negative alteration in cognition and mood. The number of symptoms needed from each category varies based on the child’s age, with differing cutoffs based on whether the child is younger or older than 6 years old. Moreover, symptoms must be present for at least 1 month.5
Trauma can be assessed in the office by using a focused interview that includes the full DSM diagnostic criteria. There are additional trauma rating screeners and assessment tools that can be used including the Child PTSD Symptom Scale, Child Trauma Screening Questionnaire, UCLA Posttraumatic Stress Disorder Reaction Index, and the Trauma Symptom Checklist for Children, to name a few. Many of these allow for multiple informants, including the child/adolescent, thereby allowing for varying perspectives regarding trauma reactions.
Treatment options
Familiarity with evidence-based treatment for trauma may be useful to ensure that referral is targeted for the patient/family. There are no Food and Drug Administrations–approved medications for children with PTSD, though medications can be used to target specific PTSD symptoms (e.g. prazosin for trauma-related nightmares) as well as commonly comorbid conditions such as depression. Becoming familiar with the available therapeutic modalities offered in your area is recommended.
Highlighting trauma-focused cognitive behavioral therapy (TF-CBT)
The treatment with the most research evidence for traumatized children is trauma-focused cognitive behavioral therapy (TF-CBT), which is a 12- to 25-session therapeutic intervention for patients 3-18 years old (with some evidence for young adults as well) with PTSD and/or trauma-related behaviors. TF-CBT uses a components-based treatment model encompassed by the PRACTICE acronym/mnemonic.6,7
- P – Psychoeducation and parenting skills.
- R – Relaxation techniques: Focused breathing, progressive muscle relaxation, and teaching the child to control their thoughts (thought stopping).
- A – Affective expression and regulation (feeling identification): To help the child and parent learn to control their emotional reaction to reminders by expanding their emotional vocabulary, enhancing their skills in identification and expression of emotions, and encouraging self-soothing activities
- C – Cognitive coping and processing: Through this component, the child learns to understand the relationships between thoughts, feelings, and behaviors and think in new and healthier ways.
- T – Trauma narrative and processing: Gradual exposure exercises including verbal, written, and/or symbolic recounting of traumatic event(s) so the child learns to be able to discuss the events when they choose to in ways that do not produce overwhelming emotions. Following the completion of the narrative, clients are supported in identifying, challenging, and correcting cognitive distortions and dysfunctional beliefs.
- I – In vivo exposure: Encourage the gradual exposure to innocuous trauma reminders in the child’s environment so the child learns they can control their emotional reactions to things that remind them of the trauma, starting with nonthreatening examples of reminders.
- C – Conjoint parent/child sessions: Sessions generally deal with psycho-education, sharing the trauma narrative, anxiety management, and correction of cognitive distortions. The family works to enhance communication and create opportunities for therapeutic discussion regarding the trauma.
- E – Enhancing personal safety and future growth: Provide training and education with respect to personal safety skills and healthy sexuality and interpersonal relationships; encourage the utilization of skills learned in managing future stressors and/or trauma reminders.
Of note, some elements of this therapy that could possibly be easily incorporated into a primary care office visit include relaxation techniques and focus on coping skills/strategies.
Summary
Children and adolescents often present with trauma-related symptoms to the primary care office. Having increasing familiarity with PTSD diagnostic criteria and treatment modalities will likely lead to increased confidence and comfort recognizing symptoms and when placing a referral. This may also lead to shorter wait times for receiving targeted treatment and ultimately should lead to better outcomes for affected children and families.
Dr. Abdul-Kareem is at the University of Vermont, Burlington.
References
1. National Survey of Children’s Health (2016 - present). https://nschdata.org/browse/survey.
2. Adverse Childhood Experiences (ACEs). Centers for Disease Control and Prevention. https://www.cdc.gov/violenceprevention/aces/index.html].
3. Post-Traumatic Stress Disorder (PTSD). National Institute of Mental Health. https://www.nimh.nih.gov/health/statistics/post-traumatic-stress-disorder-ptsd,
4. Martin A et al. Lewis’s Child and Adolescent Psychiatry (5th edition). Lippincott Williams & Wilkins: Philadelphia, 2017.
5. American Psychiatric Association. Neurodevelopmental disorders. In: DSM-5. 2013.
6. Trauma-Focused Cognitive Behavioral Therapy. The National Child Traumatic Stress Network. https://www.nctsn.org/interventions/trauma-focused-cognitive-behavioral-therapy.
7. Trauma-Focused Cognitive-Behavioral Therapy (TF-CBT). California Evidence-Based Clearinghouse for Child Welfare. https://www.cebc4cw.org/program/trauma-focused-cognitive-behavioral-therapy/.
High deductible insurance linked to delayed advanced cancer diagnosis
In oncology, delayed care may result in a failed opportunity to achieve remission. Delays in diagnosis can result in patients having to undergo more extensive surgery, radiation exposure, or more intensive drug therapy than if their disease had been detected at an early stage.
Now, researchers at Harvard Medical School, Boston, report that
Using national insurance claims data, the authors conducted an observational study to examine what happened when some workers with employer-based insurance were switched from low-deductible to high-deductible plans, compared with a control group of workers who remained on low-deductible plans.
After the switch, workers shunted into high-deductible plans had a longer time to first diagnosis of a metastatic cancer, indicating delayed detection of advanced disease, compared with controls. The difference translated into a delay in diagnosis of metastatic disease of nearly 5 months, reported Nico Trad, BA, a fourth-year medical student at Dana-Farber Cancer Institute, Boston.
“The takeaway here is that these plans were associated with delayed detection of metastatic cancer. We did not assess the mechanism, but it’s a reasonable assumption to make that increased cost-sharing is having some adverse impacts on people’s willingness to seek care. And although we didn’t study potential impacts, we might anticipate that a delayed diagnosis might also lead to delayed engagement with palliative care,” he said in an oral abstract presentation at the annual meeting of the American Society of Clinical Oncology.
“A delay in initiation of symptom-relieving therapies and a delayed presentation might also lead to greater dissemination of disease throughout the body, which also has the potential to limit therapeutic options,” he added.
‘Deductible relief day’
Mr. Trad said that in 2022 more than half of employees are covered by high-deductible health plans, compared with only about 10% in 2006.
This major shift in cost burden coincided with President Joseph Biden’s announcement in early 2022 of the “Cancer Moonshot,” program with the goal of reducing cancer mortality by 50% over the next 25 years.
“Part of that is cancer prevention and control, which involves timely detection of cancer so that we can treat it early and have better outcomes,” he said.
High-deductible health plans ostensibly provide motivation for patients to shop for lower-priced care and avoid unnecessary or low-quality care, but making patients shell out more upfront before their insurance kicks in, while it reduced health care utilization, can also reduce the quality of care, he said.
In 2022, “Deductible Relief Day,” the day in which the average patient has satisfied the deductible and insurance starts to pick up more of the tab, occurred in mid-May, compared with late February in 2006.
Insurance claims data
Mr. Trad and colleagues used health insurance claims data from a nationally representative cohort of privately insured patients in a national commercial and Medicare Advantage database. They excluded patients 65 and older who were eligible for Medicare because it does not have high-deductible options.
The study cohort included 345,401 adults from the ages of 18 to 64 whose employers mandated a switch from a low-deductible plan which was defined as $500 or less, to a high-deductible plan defined as $1,000 or more. Controls were 1,654,775 contemporaneous adults whose employers offered only low-deductible plans. Both groups had a 1-year baseline period when all members were enrolled in low deductible plans.
To minimize the possibility of confounding, the investigators matched the participants by age, gender, race/ethnicity, morbidity according to Adjusted Clinical Group score, poverty level, geographic region, employer size, baseline primary cancer, baseline medical and pharmacy costs, and follow-up duration.
During the baseline period, the hazard ratio for time to a first observed metastatic cancer diagnosis in the main cohort, compared with controls, was 0.96 with a nonsignificant P value, indicating no difference in the time to diagnosis between the groups.
During a maximum 13.5 years of follow-up, however, the participants who had been switched after a year to a high-deductible plan had a significantly longer time to first metastatic diagnosis (HR, 0.88; P = .01), indicating delayed diagnosis relative to controls. This difference translated to a delay of 4.6 months associated with the higher out-of-pocket costs plans.
According to a systematic review and meta-analysis published online in 2020, a 1-month delay in treatment for many types of cancer can translate into a 6% to 13% higher risk for death, a risk that continues to increase with further delays.
The investigators acknowledged that the study was limited by the use of retrospective claims-based data, which not contain information on how the patients fared after diagnosis.
“I would say in terms of policy relevance that this really points to the need for new and innovative insurance models that, No. 1, reduce the cost-sharing burden for patients so that they’re not deterred from seeking care, and No. 2, that align rather than contradict the goal of improving population-level survival from cancer,” Mr. Trad said.
Further evidence of a flawed system
The study adds to an already strong body of evidence showing that high-deductible plans can have a negative impact on health, said Sara R. Collins, vice president for health care coverage and access at the Commonwealth Fund, a New York–based private foundation dedicated to improving health care.
“This is really the latest evidence on top of years of research that shows that high-deductible health plans lead people to make decisions that are not in the best interest of their health,” said Ms. Collins, who is not affiliated with the study presented at ASCO.
“We have a health care cost problem in the United States that far exceeds that of other high-income countries. Insurers try to solve it by shifting the costs to consumers and using other measures to restrict people’s use of health care, and often needed health care like this. The result is less access to needed care, and long-term adverse health consequences and their associated costs to patients and the health system generally,” she said.
The real driver of health care costs is not utilization, but the prices that insurers and providers negotiate in their service contracts, she explained.
“Prices are the central problem, insurers have control over those prices in their negotiations with providers. So unless we can gain control of that driver, patients are going to continue to suffer unnecessarily from both the short- and long-term effects of insurers who use tools to reduce their access to care,” she said.
In oncology, delayed care may result in a failed opportunity to achieve remission. Delays in diagnosis can result in patients having to undergo more extensive surgery, radiation exposure, or more intensive drug therapy than if their disease had been detected at an early stage.
Now, researchers at Harvard Medical School, Boston, report that
Using national insurance claims data, the authors conducted an observational study to examine what happened when some workers with employer-based insurance were switched from low-deductible to high-deductible plans, compared with a control group of workers who remained on low-deductible plans.
After the switch, workers shunted into high-deductible plans had a longer time to first diagnosis of a metastatic cancer, indicating delayed detection of advanced disease, compared with controls. The difference translated into a delay in diagnosis of metastatic disease of nearly 5 months, reported Nico Trad, BA, a fourth-year medical student at Dana-Farber Cancer Institute, Boston.
“The takeaway here is that these plans were associated with delayed detection of metastatic cancer. We did not assess the mechanism, but it’s a reasonable assumption to make that increased cost-sharing is having some adverse impacts on people’s willingness to seek care. And although we didn’t study potential impacts, we might anticipate that a delayed diagnosis might also lead to delayed engagement with palliative care,” he said in an oral abstract presentation at the annual meeting of the American Society of Clinical Oncology.
“A delay in initiation of symptom-relieving therapies and a delayed presentation might also lead to greater dissemination of disease throughout the body, which also has the potential to limit therapeutic options,” he added.
‘Deductible relief day’
Mr. Trad said that in 2022 more than half of employees are covered by high-deductible health plans, compared with only about 10% in 2006.
This major shift in cost burden coincided with President Joseph Biden’s announcement in early 2022 of the “Cancer Moonshot,” program with the goal of reducing cancer mortality by 50% over the next 25 years.
“Part of that is cancer prevention and control, which involves timely detection of cancer so that we can treat it early and have better outcomes,” he said.
High-deductible health plans ostensibly provide motivation for patients to shop for lower-priced care and avoid unnecessary or low-quality care, but making patients shell out more upfront before their insurance kicks in, while it reduced health care utilization, can also reduce the quality of care, he said.
In 2022, “Deductible Relief Day,” the day in which the average patient has satisfied the deductible and insurance starts to pick up more of the tab, occurred in mid-May, compared with late February in 2006.
Insurance claims data
Mr. Trad and colleagues used health insurance claims data from a nationally representative cohort of privately insured patients in a national commercial and Medicare Advantage database. They excluded patients 65 and older who were eligible for Medicare because it does not have high-deductible options.
The study cohort included 345,401 adults from the ages of 18 to 64 whose employers mandated a switch from a low-deductible plan which was defined as $500 or less, to a high-deductible plan defined as $1,000 or more. Controls were 1,654,775 contemporaneous adults whose employers offered only low-deductible plans. Both groups had a 1-year baseline period when all members were enrolled in low deductible plans.
To minimize the possibility of confounding, the investigators matched the participants by age, gender, race/ethnicity, morbidity according to Adjusted Clinical Group score, poverty level, geographic region, employer size, baseline primary cancer, baseline medical and pharmacy costs, and follow-up duration.
During the baseline period, the hazard ratio for time to a first observed metastatic cancer diagnosis in the main cohort, compared with controls, was 0.96 with a nonsignificant P value, indicating no difference in the time to diagnosis between the groups.
During a maximum 13.5 years of follow-up, however, the participants who had been switched after a year to a high-deductible plan had a significantly longer time to first metastatic diagnosis (HR, 0.88; P = .01), indicating delayed diagnosis relative to controls. This difference translated to a delay of 4.6 months associated with the higher out-of-pocket costs plans.
According to a systematic review and meta-analysis published online in 2020, a 1-month delay in treatment for many types of cancer can translate into a 6% to 13% higher risk for death, a risk that continues to increase with further delays.
The investigators acknowledged that the study was limited by the use of retrospective claims-based data, which not contain information on how the patients fared after diagnosis.
“I would say in terms of policy relevance that this really points to the need for new and innovative insurance models that, No. 1, reduce the cost-sharing burden for patients so that they’re not deterred from seeking care, and No. 2, that align rather than contradict the goal of improving population-level survival from cancer,” Mr. Trad said.
Further evidence of a flawed system
The study adds to an already strong body of evidence showing that high-deductible plans can have a negative impact on health, said Sara R. Collins, vice president for health care coverage and access at the Commonwealth Fund, a New York–based private foundation dedicated to improving health care.
“This is really the latest evidence on top of years of research that shows that high-deductible health plans lead people to make decisions that are not in the best interest of their health,” said Ms. Collins, who is not affiliated with the study presented at ASCO.
“We have a health care cost problem in the United States that far exceeds that of other high-income countries. Insurers try to solve it by shifting the costs to consumers and using other measures to restrict people’s use of health care, and often needed health care like this. The result is less access to needed care, and long-term adverse health consequences and their associated costs to patients and the health system generally,” she said.
The real driver of health care costs is not utilization, but the prices that insurers and providers negotiate in their service contracts, she explained.
“Prices are the central problem, insurers have control over those prices in their negotiations with providers. So unless we can gain control of that driver, patients are going to continue to suffer unnecessarily from both the short- and long-term effects of insurers who use tools to reduce their access to care,” she said.
In oncology, delayed care may result in a failed opportunity to achieve remission. Delays in diagnosis can result in patients having to undergo more extensive surgery, radiation exposure, or more intensive drug therapy than if their disease had been detected at an early stage.
Now, researchers at Harvard Medical School, Boston, report that
Using national insurance claims data, the authors conducted an observational study to examine what happened when some workers with employer-based insurance were switched from low-deductible to high-deductible plans, compared with a control group of workers who remained on low-deductible plans.
After the switch, workers shunted into high-deductible plans had a longer time to first diagnosis of a metastatic cancer, indicating delayed detection of advanced disease, compared with controls. The difference translated into a delay in diagnosis of metastatic disease of nearly 5 months, reported Nico Trad, BA, a fourth-year medical student at Dana-Farber Cancer Institute, Boston.
“The takeaway here is that these plans were associated with delayed detection of metastatic cancer. We did not assess the mechanism, but it’s a reasonable assumption to make that increased cost-sharing is having some adverse impacts on people’s willingness to seek care. And although we didn’t study potential impacts, we might anticipate that a delayed diagnosis might also lead to delayed engagement with palliative care,” he said in an oral abstract presentation at the annual meeting of the American Society of Clinical Oncology.
“A delay in initiation of symptom-relieving therapies and a delayed presentation might also lead to greater dissemination of disease throughout the body, which also has the potential to limit therapeutic options,” he added.
‘Deductible relief day’
Mr. Trad said that in 2022 more than half of employees are covered by high-deductible health plans, compared with only about 10% in 2006.
This major shift in cost burden coincided with President Joseph Biden’s announcement in early 2022 of the “Cancer Moonshot,” program with the goal of reducing cancer mortality by 50% over the next 25 years.
“Part of that is cancer prevention and control, which involves timely detection of cancer so that we can treat it early and have better outcomes,” he said.
High-deductible health plans ostensibly provide motivation for patients to shop for lower-priced care and avoid unnecessary or low-quality care, but making patients shell out more upfront before their insurance kicks in, while it reduced health care utilization, can also reduce the quality of care, he said.
In 2022, “Deductible Relief Day,” the day in which the average patient has satisfied the deductible and insurance starts to pick up more of the tab, occurred in mid-May, compared with late February in 2006.
Insurance claims data
Mr. Trad and colleagues used health insurance claims data from a nationally representative cohort of privately insured patients in a national commercial and Medicare Advantage database. They excluded patients 65 and older who were eligible for Medicare because it does not have high-deductible options.
The study cohort included 345,401 adults from the ages of 18 to 64 whose employers mandated a switch from a low-deductible plan which was defined as $500 or less, to a high-deductible plan defined as $1,000 or more. Controls were 1,654,775 contemporaneous adults whose employers offered only low-deductible plans. Both groups had a 1-year baseline period when all members were enrolled in low deductible plans.
To minimize the possibility of confounding, the investigators matched the participants by age, gender, race/ethnicity, morbidity according to Adjusted Clinical Group score, poverty level, geographic region, employer size, baseline primary cancer, baseline medical and pharmacy costs, and follow-up duration.
During the baseline period, the hazard ratio for time to a first observed metastatic cancer diagnosis in the main cohort, compared with controls, was 0.96 with a nonsignificant P value, indicating no difference in the time to diagnosis between the groups.
During a maximum 13.5 years of follow-up, however, the participants who had been switched after a year to a high-deductible plan had a significantly longer time to first metastatic diagnosis (HR, 0.88; P = .01), indicating delayed diagnosis relative to controls. This difference translated to a delay of 4.6 months associated with the higher out-of-pocket costs plans.
According to a systematic review and meta-analysis published online in 2020, a 1-month delay in treatment for many types of cancer can translate into a 6% to 13% higher risk for death, a risk that continues to increase with further delays.
The investigators acknowledged that the study was limited by the use of retrospective claims-based data, which not contain information on how the patients fared after diagnosis.
“I would say in terms of policy relevance that this really points to the need for new and innovative insurance models that, No. 1, reduce the cost-sharing burden for patients so that they’re not deterred from seeking care, and No. 2, that align rather than contradict the goal of improving population-level survival from cancer,” Mr. Trad said.
Further evidence of a flawed system
The study adds to an already strong body of evidence showing that high-deductible plans can have a negative impact on health, said Sara R. Collins, vice president for health care coverage and access at the Commonwealth Fund, a New York–based private foundation dedicated to improving health care.
“This is really the latest evidence on top of years of research that shows that high-deductible health plans lead people to make decisions that are not in the best interest of their health,” said Ms. Collins, who is not affiliated with the study presented at ASCO.
“We have a health care cost problem in the United States that far exceeds that of other high-income countries. Insurers try to solve it by shifting the costs to consumers and using other measures to restrict people’s use of health care, and often needed health care like this. The result is less access to needed care, and long-term adverse health consequences and their associated costs to patients and the health system generally,” she said.
The real driver of health care costs is not utilization, but the prices that insurers and providers negotiate in their service contracts, she explained.
“Prices are the central problem, insurers have control over those prices in their negotiations with providers. So unless we can gain control of that driver, patients are going to continue to suffer unnecessarily from both the short- and long-term effects of insurers who use tools to reduce their access to care,” she said.
FROM ASCO 2022
New KRAS inhibitor shows promise in NSCLC
In a phase 2 cohort study, who had previously been treated with platinum-based chemotherapy and immune therapy.
Adagrasib targets KRAS (G12C), which had long been thought undruggable until research published in 2013 revealed a new binding pocket that did not compete directly against the protein’s natural binding partner. The new trial further validates the approach. “It supports that clinically effective targeted therapies can be developed for patients with KRAS (G12C)–mutant NSCLC,” said Pasi Jänne, MD, PhD, who is the lead author of the study describing the new results published online in the New England Journal of Medicine.
KRAS is the most frequently mutated oncogene in human cancers. A mutated form is found in about 25% of NSCLCs. KRAS plays a key role in cell signaling governing growth, maturation, and cell death. The mutated form is linked to cancer growth and spread. Patients with mutated KRAS have few effective treatment options.
Adagrasib is currently under study and not yet approved by the Food and Drug Administration. However, sotorasib (Lumakras, Amgen), which also inhibits KRAS (G12C), was approved in May 2021 by the FDA for KRAS (G12C)–mutated NSCLC. There are some key differences between the drugs. Adagrasib has a half-life of 23 hours versus 5 hours for sotorasib, and the newer drug has the potential to penetrate the central nervous system. That could be an important consideration in NSCLC since it often metastasizes to the brain. “Having pharmacological approaches to treat brain metastases is a wonderful new therapeutic option for lung cancer patients,” said Dr. Jänne, who is director of the Lowe Center for Thoracic Oncology at Dana Farber Cancer Institute, Boston.
Adagrasib is being investigated as part of the KRYSTAL-1 study, alone and as part of combinations in various solid tumors. Previously treated NSCLC KRAS (G12C) patients are also being enrolled in a phase 3 study of adagrasib combined with docetaxel, as well as another phase 2 study of adagrasib combined with pembrolizumab as first-line therapy for NSCLC KRAS (G12C).
Adagrasib is likely to remain a second-line therapy following chemotherapy and immunotherapy. “The activity by itself at the moment is not sufficient to be a first-line treatment. That may change in the future in combination with a standard of care agent or in a subset of patients with KRAS (G12C)–mutant NSCLC, although no subset with higher efficacy has been identified to date. Identification of predictive biomarkers for patients likely to benefit from single agent or an adagrasib combination treatment remains a high priority,” Dr. Jänne said.
The study included 116 patients who had previously been treated with platinum-based chemotherapy and anti–programmed death 1 or programmed death–ligand 1 therapy. They received 600 mg oral adagrasib twice per day over a median follow-up period of 12.9 months. About 42.9% (95% confidence interval, 33.5%-52.6%) experienced a confirmed objective response with a median duration of 8.5 months (95% CI, 6.2-13.8 months). The median progression-free survival was 6.5 months (95% CI, 4.7-8.4 months). After a median follow-up of 15.6 months, the median overall survival was 12.6 months (95% CI, 9.2-19.2 months). The estimated overall survival at 1 year was 50.8% (95% CI, 40.9%-60.0%).
33 patients had stable central nervous system metastases that had been previously treated. About 33.3% had an intracranial confirmed objective response (95% CI, 18.0-51.8%) with a median duration of response of 11.2 months (95% CI, 2.99 months to not available).
Adverse events are similar to what is seen with other targeted therapies, according to Dr. Jänne. 97.4% of patient reported a treatment-related adverse event; 52.6% had grade 1-2 adverse events, and 44.8% had grade 3 adverse events. 6.9% discontinued the drug as a result.
Dr. Jänne has consulted for Mirati Therapeutics and is a member of its scientific advisory board. The study was funded by Mirati Therapeutics.
In a phase 2 cohort study, who had previously been treated with platinum-based chemotherapy and immune therapy.
Adagrasib targets KRAS (G12C), which had long been thought undruggable until research published in 2013 revealed a new binding pocket that did not compete directly against the protein’s natural binding partner. The new trial further validates the approach. “It supports that clinically effective targeted therapies can be developed for patients with KRAS (G12C)–mutant NSCLC,” said Pasi Jänne, MD, PhD, who is the lead author of the study describing the new results published online in the New England Journal of Medicine.
KRAS is the most frequently mutated oncogene in human cancers. A mutated form is found in about 25% of NSCLCs. KRAS plays a key role in cell signaling governing growth, maturation, and cell death. The mutated form is linked to cancer growth and spread. Patients with mutated KRAS have few effective treatment options.
Adagrasib is currently under study and not yet approved by the Food and Drug Administration. However, sotorasib (Lumakras, Amgen), which also inhibits KRAS (G12C), was approved in May 2021 by the FDA for KRAS (G12C)–mutated NSCLC. There are some key differences between the drugs. Adagrasib has a half-life of 23 hours versus 5 hours for sotorasib, and the newer drug has the potential to penetrate the central nervous system. That could be an important consideration in NSCLC since it often metastasizes to the brain. “Having pharmacological approaches to treat brain metastases is a wonderful new therapeutic option for lung cancer patients,” said Dr. Jänne, who is director of the Lowe Center for Thoracic Oncology at Dana Farber Cancer Institute, Boston.
Adagrasib is being investigated as part of the KRYSTAL-1 study, alone and as part of combinations in various solid tumors. Previously treated NSCLC KRAS (G12C) patients are also being enrolled in a phase 3 study of adagrasib combined with docetaxel, as well as another phase 2 study of adagrasib combined with pembrolizumab as first-line therapy for NSCLC KRAS (G12C).
Adagrasib is likely to remain a second-line therapy following chemotherapy and immunotherapy. “The activity by itself at the moment is not sufficient to be a first-line treatment. That may change in the future in combination with a standard of care agent or in a subset of patients with KRAS (G12C)–mutant NSCLC, although no subset with higher efficacy has been identified to date. Identification of predictive biomarkers for patients likely to benefit from single agent or an adagrasib combination treatment remains a high priority,” Dr. Jänne said.
The study included 116 patients who had previously been treated with platinum-based chemotherapy and anti–programmed death 1 or programmed death–ligand 1 therapy. They received 600 mg oral adagrasib twice per day over a median follow-up period of 12.9 months. About 42.9% (95% confidence interval, 33.5%-52.6%) experienced a confirmed objective response with a median duration of 8.5 months (95% CI, 6.2-13.8 months). The median progression-free survival was 6.5 months (95% CI, 4.7-8.4 months). After a median follow-up of 15.6 months, the median overall survival was 12.6 months (95% CI, 9.2-19.2 months). The estimated overall survival at 1 year was 50.8% (95% CI, 40.9%-60.0%).
33 patients had stable central nervous system metastases that had been previously treated. About 33.3% had an intracranial confirmed objective response (95% CI, 18.0-51.8%) with a median duration of response of 11.2 months (95% CI, 2.99 months to not available).
Adverse events are similar to what is seen with other targeted therapies, according to Dr. Jänne. 97.4% of patient reported a treatment-related adverse event; 52.6% had grade 1-2 adverse events, and 44.8% had grade 3 adverse events. 6.9% discontinued the drug as a result.
Dr. Jänne has consulted for Mirati Therapeutics and is a member of its scientific advisory board. The study was funded by Mirati Therapeutics.
In a phase 2 cohort study, who had previously been treated with platinum-based chemotherapy and immune therapy.
Adagrasib targets KRAS (G12C), which had long been thought undruggable until research published in 2013 revealed a new binding pocket that did not compete directly against the protein’s natural binding partner. The new trial further validates the approach. “It supports that clinically effective targeted therapies can be developed for patients with KRAS (G12C)–mutant NSCLC,” said Pasi Jänne, MD, PhD, who is the lead author of the study describing the new results published online in the New England Journal of Medicine.
KRAS is the most frequently mutated oncogene in human cancers. A mutated form is found in about 25% of NSCLCs. KRAS plays a key role in cell signaling governing growth, maturation, and cell death. The mutated form is linked to cancer growth and spread. Patients with mutated KRAS have few effective treatment options.
Adagrasib is currently under study and not yet approved by the Food and Drug Administration. However, sotorasib (Lumakras, Amgen), which also inhibits KRAS (G12C), was approved in May 2021 by the FDA for KRAS (G12C)–mutated NSCLC. There are some key differences between the drugs. Adagrasib has a half-life of 23 hours versus 5 hours for sotorasib, and the newer drug has the potential to penetrate the central nervous system. That could be an important consideration in NSCLC since it often metastasizes to the brain. “Having pharmacological approaches to treat brain metastases is a wonderful new therapeutic option for lung cancer patients,” said Dr. Jänne, who is director of the Lowe Center for Thoracic Oncology at Dana Farber Cancer Institute, Boston.
Adagrasib is being investigated as part of the KRYSTAL-1 study, alone and as part of combinations in various solid tumors. Previously treated NSCLC KRAS (G12C) patients are also being enrolled in a phase 3 study of adagrasib combined with docetaxel, as well as another phase 2 study of adagrasib combined with pembrolizumab as first-line therapy for NSCLC KRAS (G12C).
Adagrasib is likely to remain a second-line therapy following chemotherapy and immunotherapy. “The activity by itself at the moment is not sufficient to be a first-line treatment. That may change in the future in combination with a standard of care agent or in a subset of patients with KRAS (G12C)–mutant NSCLC, although no subset with higher efficacy has been identified to date. Identification of predictive biomarkers for patients likely to benefit from single agent or an adagrasib combination treatment remains a high priority,” Dr. Jänne said.
The study included 116 patients who had previously been treated with platinum-based chemotherapy and anti–programmed death 1 or programmed death–ligand 1 therapy. They received 600 mg oral adagrasib twice per day over a median follow-up period of 12.9 months. About 42.9% (95% confidence interval, 33.5%-52.6%) experienced a confirmed objective response with a median duration of 8.5 months (95% CI, 6.2-13.8 months). The median progression-free survival was 6.5 months (95% CI, 4.7-8.4 months). After a median follow-up of 15.6 months, the median overall survival was 12.6 months (95% CI, 9.2-19.2 months). The estimated overall survival at 1 year was 50.8% (95% CI, 40.9%-60.0%).
33 patients had stable central nervous system metastases that had been previously treated. About 33.3% had an intracranial confirmed objective response (95% CI, 18.0-51.8%) with a median duration of response of 11.2 months (95% CI, 2.99 months to not available).
Adverse events are similar to what is seen with other targeted therapies, according to Dr. Jänne. 97.4% of patient reported a treatment-related adverse event; 52.6% had grade 1-2 adverse events, and 44.8% had grade 3 adverse events. 6.9% discontinued the drug as a result.
Dr. Jänne has consulted for Mirati Therapeutics and is a member of its scientific advisory board. The study was funded by Mirati Therapeutics.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
FDA approves combination pegloticase and methotrexate for refractory gout
Pegloticase, which has been available for 12 years, is a pegylated uric acid specific enzyme that lowers sUA by converting it to allantoin.
Though pegloticase is effective in treating chronic gout in patients refractory to conventional treatment, approximately 92% of patients develop antibodies against the drug, resulting in reduced efficacy.
Based on the immunomodulatory effects of methotrexate, researchers of the randomized, placebo-controlled MIRROR trial sought to determine whether combination treatment of pegloticase with methotrexate (multiple brands) would prevent the development of anti-drug antibodies.
Findings from the phase 4 trial found that co-administration of pegloticase and methotrexate reduced the formation of new anti-PEG antibodies. In the group receiving methotrexate and pegloticase, 23.2% (22 out of 95) of patients had an increase in anti-PEG antibodies, compared with 50% (24 of 48) in the pegloticase plus placebo group, according to a recent company press release.
Nearly three-quarters (71%) of participants in the group pretreated with methotrexate, followed by combination pegloticase-methotrexate, had sUA levels that dopped to below 6 mg/dL during the 52-week study. By comparison, 38.5% of participants in the pegloticase and placebo group reached the endpoint. Though gout flare occurred in both groups, methotrexate did not appear to increase the risk for adverse events or gout flare.
The study, led by John Botson, MD, RPh, CCD, a rheumatologist in Anchorage, Alaska, concluded that these measurements demonstrated a significant improvement from traditional pegloticase-only treatment of gout. “This trial confirms not only improved efficacy but improved safety in patients treated with pegloticase in combination with methotrexate 15 mg orally once weekly,” Dr. Botson said last month in an interview with this news organization.
The study was funded by Horizon. Dr. Botson reports receiving research support from Horizon and Radius Health and speaker fees from AbbVie, Amgen, Aurinia, ChemoCentryx, Horizon, Eli Lilly, and Novartis.
A version of this article first appeared on Medscape.com.
Pegloticase, which has been available for 12 years, is a pegylated uric acid specific enzyme that lowers sUA by converting it to allantoin.
Though pegloticase is effective in treating chronic gout in patients refractory to conventional treatment, approximately 92% of patients develop antibodies against the drug, resulting in reduced efficacy.
Based on the immunomodulatory effects of methotrexate, researchers of the randomized, placebo-controlled MIRROR trial sought to determine whether combination treatment of pegloticase with methotrexate (multiple brands) would prevent the development of anti-drug antibodies.
Findings from the phase 4 trial found that co-administration of pegloticase and methotrexate reduced the formation of new anti-PEG antibodies. In the group receiving methotrexate and pegloticase, 23.2% (22 out of 95) of patients had an increase in anti-PEG antibodies, compared with 50% (24 of 48) in the pegloticase plus placebo group, according to a recent company press release.
Nearly three-quarters (71%) of participants in the group pretreated with methotrexate, followed by combination pegloticase-methotrexate, had sUA levels that dopped to below 6 mg/dL during the 52-week study. By comparison, 38.5% of participants in the pegloticase and placebo group reached the endpoint. Though gout flare occurred in both groups, methotrexate did not appear to increase the risk for adverse events or gout flare.
The study, led by John Botson, MD, RPh, CCD, a rheumatologist in Anchorage, Alaska, concluded that these measurements demonstrated a significant improvement from traditional pegloticase-only treatment of gout. “This trial confirms not only improved efficacy but improved safety in patients treated with pegloticase in combination with methotrexate 15 mg orally once weekly,” Dr. Botson said last month in an interview with this news organization.
The study was funded by Horizon. Dr. Botson reports receiving research support from Horizon and Radius Health and speaker fees from AbbVie, Amgen, Aurinia, ChemoCentryx, Horizon, Eli Lilly, and Novartis.
A version of this article first appeared on Medscape.com.
Pegloticase, which has been available for 12 years, is a pegylated uric acid specific enzyme that lowers sUA by converting it to allantoin.
Though pegloticase is effective in treating chronic gout in patients refractory to conventional treatment, approximately 92% of patients develop antibodies against the drug, resulting in reduced efficacy.
Based on the immunomodulatory effects of methotrexate, researchers of the randomized, placebo-controlled MIRROR trial sought to determine whether combination treatment of pegloticase with methotrexate (multiple brands) would prevent the development of anti-drug antibodies.
Findings from the phase 4 trial found that co-administration of pegloticase and methotrexate reduced the formation of new anti-PEG antibodies. In the group receiving methotrexate and pegloticase, 23.2% (22 out of 95) of patients had an increase in anti-PEG antibodies, compared with 50% (24 of 48) in the pegloticase plus placebo group, according to a recent company press release.
Nearly three-quarters (71%) of participants in the group pretreated with methotrexate, followed by combination pegloticase-methotrexate, had sUA levels that dopped to below 6 mg/dL during the 52-week study. By comparison, 38.5% of participants in the pegloticase and placebo group reached the endpoint. Though gout flare occurred in both groups, methotrexate did not appear to increase the risk for adverse events or gout flare.
The study, led by John Botson, MD, RPh, CCD, a rheumatologist in Anchorage, Alaska, concluded that these measurements demonstrated a significant improvement from traditional pegloticase-only treatment of gout. “This trial confirms not only improved efficacy but improved safety in patients treated with pegloticase in combination with methotrexate 15 mg orally once weekly,” Dr. Botson said last month in an interview with this news organization.
The study was funded by Horizon. Dr. Botson reports receiving research support from Horizon and Radius Health and speaker fees from AbbVie, Amgen, Aurinia, ChemoCentryx, Horizon, Eli Lilly, and Novartis.
A version of this article first appeared on Medscape.com.
Topical gel for epidermolysis bullosa shows ongoing benefit
GLASGOW, Scotland – the phase 3 safety and efficacy study of the treatment.
Over 200 patients from the trial, including 105 who began treatment with a control gel, continued taking oleogel-S10 after 90 days. The current interim analysis at 12 months indicates there was a 55% reduction in the proportion of the body affected, compared with baseline.
Moreover, reductions in skin activity scores seen in the double-blind phase of the trial were maintained during the open-label extension. About 6% of patients experienced adverse events that led to withdrawal from the study.
The results show that oleogel-S10 was associated with “accelerated wound healing,” said study presenter Tracey Cunningham, MD, chief medical officer, Amryt Pharmaceuticals DAC, Dublin, which is developing the topical agent. “There were no new safety signals with this longer exposure to oleogel-S10, and patients had sustained improvement in wound burden,” she added.
The research was presented at the British Association of Dermatologists (BAD) 2022 Annual Meeting on July 6.
In April, European Medicines Agency recommended approval of oleogel-S10 for the treatment of partial-thickness skin wounds associated with dystrophic and junctional EB for patients aged 6 months and older.
However, just a month earlier, the U.S. Food and Drug Administration declined to approve the topical agent for use in EB, even after it extended its review by 3 months to include additional analyses of data previously submitted by the company.
In the post-presentation discussion, Dr. Cunningham said that the FDA had “not been satisfied at this point with the information that we have given them,” adding, “We don’t agree with the decision, and we will be appealing.”
Raman K. Madan, MD, a dermatologist at Northwell Health, Huntington, New York, who was not involved in the study, said that the reductions in wound healing seen in the study are “meaningful” and that the numbers represent a “big breakthrough.”
He told this news organization that there are “very few products on the market” for EB and that having an option for patients “would be amazing.”
“The big issue here would be cost and coverage for patients,” he said. If approved, “hopefully” it will be affordable, he added.
Dr. Madan noted that from his perspective, the majority of the reactions to the topical gel were “mild,” and there are “a lot of confounding factors” underlying the number of serious adverse events. “These patients with epidermolysis are prone to some of these issues regardless of treatment,” he said.
During her presentation, Dr. Cunningham noted that EB is a rare, debilitating condition that is characterized by varying degrees of skin fragility, blisters, and impaired wound healing that in turn lead to serious complications that affect quality of life.
While wound management is a “fundamental priority” for patients living with EB, she said, there is a “high, unmet” clinical need.
To those ends, EASE was the largest randomized controlled phase 3 efficacy and safety study in EB. In the study, 252 patients were allocated to receive oleogel-S10 or control gel plus standard-of-care nonadhesive wound dressing.
The double-blind phase of the trial met its primary endpoint: A higher proportion of patients who were given oleogel-S10 achieved first complete closure of the EB target wound by day 45, compared with patients who were given control gel, at 41.3% versus 28.9%. This equated to a relative risk of wound closure by day 45 of 1.44, or an odds ratio of 1.84 (P = .013).
However, as reported at the time by this news organization, the difference in time to wound healing by day 90 between the two patient groups was not statistically significant (P = .302), with 50.5% of oleogel-S10 patients achieving wound closure, versus 43.9% of those in the control group.
Dr. Cunningham discussed the open-label extension, which involved 205 patients from the double-blind phase (mean age, of 16.3 years) treated with oleogel-S10 or control gel plus standard-of-care nonadhesive wound dressing for 24 months.
In presenting the results of the first 12 months of the open-label extension, she said that oleogel-S10 led to “consistent” reductions in the body surface area percentage (BSAP) affected by EB. The overall reduction from baseline was 55% after receiving treatment for 15 months.
Between day 90 and month 12 of the open-label extension, the absolute BSAP was reduced from 7.4% to 5.4% for patients who had received oleogel-S10 from the start of the study. For those who started in the control group and then switched to the oleogel-S10 arm during the open-label extension, the reduction was from 8.3% to 6.4%.
Dr. Cunningham pointed out that a 1% reduction in BSAP equates approximately to the palmar surface of the hand.
Scores on the Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) Skin activity subscale indicated that the reductions achieved in the double-blind phase of the trial were maintained.
Among patients who received oleogel-S10 from the start of the trial, EBDASI Skin scores were reduced from 19.6 at baseline to 13.5 at 12 months’ follow-up in the open-label extension. The reduction was from 19.6 to 13.5 for those who began the trial taking control gel.
Dr. Cunningham showed that adverse events of any grade were seen in 72.0% of patients who began taking oleogel-S10 at the start of the trial and in 69.5% of those who began the trial taking control gel.
Serious adverse events were recorded in 23.0% and 20.0% of patients, respectively, while 6.0% of those who initially received oleogel-S10 and 6.7% of those initially assigned to control gel experienced adverse events that led to study withdrawal during the open-label phase.
The most frequently reported adverse events in the open-label extension were wound complications, seen in 39.5% of patients; anemia, seen in 14.1%; wound infection, seen in 9.3%; pyrexia, seen in 8.3%; and pruritus, seen in 5.9%. No more details regarding adverse events were provided.
The study was funded by Amryt Pharmaceuticals DAC. Dr. Cunningham is an employee of Amryt Pharmaceuticals. No other relevant financial relationships have been disclosed.
A version of this article first appeared on Medscape.com.
GLASGOW, Scotland – the phase 3 safety and efficacy study of the treatment.
Over 200 patients from the trial, including 105 who began treatment with a control gel, continued taking oleogel-S10 after 90 days. The current interim analysis at 12 months indicates there was a 55% reduction in the proportion of the body affected, compared with baseline.
Moreover, reductions in skin activity scores seen in the double-blind phase of the trial were maintained during the open-label extension. About 6% of patients experienced adverse events that led to withdrawal from the study.
The results show that oleogel-S10 was associated with “accelerated wound healing,” said study presenter Tracey Cunningham, MD, chief medical officer, Amryt Pharmaceuticals DAC, Dublin, which is developing the topical agent. “There were no new safety signals with this longer exposure to oleogel-S10, and patients had sustained improvement in wound burden,” she added.
The research was presented at the British Association of Dermatologists (BAD) 2022 Annual Meeting on July 6.
In April, European Medicines Agency recommended approval of oleogel-S10 for the treatment of partial-thickness skin wounds associated with dystrophic and junctional EB for patients aged 6 months and older.
However, just a month earlier, the U.S. Food and Drug Administration declined to approve the topical agent for use in EB, even after it extended its review by 3 months to include additional analyses of data previously submitted by the company.
In the post-presentation discussion, Dr. Cunningham said that the FDA had “not been satisfied at this point with the information that we have given them,” adding, “We don’t agree with the decision, and we will be appealing.”
Raman K. Madan, MD, a dermatologist at Northwell Health, Huntington, New York, who was not involved in the study, said that the reductions in wound healing seen in the study are “meaningful” and that the numbers represent a “big breakthrough.”
He told this news organization that there are “very few products on the market” for EB and that having an option for patients “would be amazing.”
“The big issue here would be cost and coverage for patients,” he said. If approved, “hopefully” it will be affordable, he added.
Dr. Madan noted that from his perspective, the majority of the reactions to the topical gel were “mild,” and there are “a lot of confounding factors” underlying the number of serious adverse events. “These patients with epidermolysis are prone to some of these issues regardless of treatment,” he said.
During her presentation, Dr. Cunningham noted that EB is a rare, debilitating condition that is characterized by varying degrees of skin fragility, blisters, and impaired wound healing that in turn lead to serious complications that affect quality of life.
While wound management is a “fundamental priority” for patients living with EB, she said, there is a “high, unmet” clinical need.
To those ends, EASE was the largest randomized controlled phase 3 efficacy and safety study in EB. In the study, 252 patients were allocated to receive oleogel-S10 or control gel plus standard-of-care nonadhesive wound dressing.
The double-blind phase of the trial met its primary endpoint: A higher proportion of patients who were given oleogel-S10 achieved first complete closure of the EB target wound by day 45, compared with patients who were given control gel, at 41.3% versus 28.9%. This equated to a relative risk of wound closure by day 45 of 1.44, or an odds ratio of 1.84 (P = .013).
However, as reported at the time by this news organization, the difference in time to wound healing by day 90 between the two patient groups was not statistically significant (P = .302), with 50.5% of oleogel-S10 patients achieving wound closure, versus 43.9% of those in the control group.
Dr. Cunningham discussed the open-label extension, which involved 205 patients from the double-blind phase (mean age, of 16.3 years) treated with oleogel-S10 or control gel plus standard-of-care nonadhesive wound dressing for 24 months.
In presenting the results of the first 12 months of the open-label extension, she said that oleogel-S10 led to “consistent” reductions in the body surface area percentage (BSAP) affected by EB. The overall reduction from baseline was 55% after receiving treatment for 15 months.
Between day 90 and month 12 of the open-label extension, the absolute BSAP was reduced from 7.4% to 5.4% for patients who had received oleogel-S10 from the start of the study. For those who started in the control group and then switched to the oleogel-S10 arm during the open-label extension, the reduction was from 8.3% to 6.4%.
Dr. Cunningham pointed out that a 1% reduction in BSAP equates approximately to the palmar surface of the hand.
Scores on the Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) Skin activity subscale indicated that the reductions achieved in the double-blind phase of the trial were maintained.
Among patients who received oleogel-S10 from the start of the trial, EBDASI Skin scores were reduced from 19.6 at baseline to 13.5 at 12 months’ follow-up in the open-label extension. The reduction was from 19.6 to 13.5 for those who began the trial taking control gel.
Dr. Cunningham showed that adverse events of any grade were seen in 72.0% of patients who began taking oleogel-S10 at the start of the trial and in 69.5% of those who began the trial taking control gel.
Serious adverse events were recorded in 23.0% and 20.0% of patients, respectively, while 6.0% of those who initially received oleogel-S10 and 6.7% of those initially assigned to control gel experienced adverse events that led to study withdrawal during the open-label phase.
The most frequently reported adverse events in the open-label extension were wound complications, seen in 39.5% of patients; anemia, seen in 14.1%; wound infection, seen in 9.3%; pyrexia, seen in 8.3%; and pruritus, seen in 5.9%. No more details regarding adverse events were provided.
The study was funded by Amryt Pharmaceuticals DAC. Dr. Cunningham is an employee of Amryt Pharmaceuticals. No other relevant financial relationships have been disclosed.
A version of this article first appeared on Medscape.com.
GLASGOW, Scotland – the phase 3 safety and efficacy study of the treatment.
Over 200 patients from the trial, including 105 who began treatment with a control gel, continued taking oleogel-S10 after 90 days. The current interim analysis at 12 months indicates there was a 55% reduction in the proportion of the body affected, compared with baseline.
Moreover, reductions in skin activity scores seen in the double-blind phase of the trial were maintained during the open-label extension. About 6% of patients experienced adverse events that led to withdrawal from the study.
The results show that oleogel-S10 was associated with “accelerated wound healing,” said study presenter Tracey Cunningham, MD, chief medical officer, Amryt Pharmaceuticals DAC, Dublin, which is developing the topical agent. “There were no new safety signals with this longer exposure to oleogel-S10, and patients had sustained improvement in wound burden,” she added.
The research was presented at the British Association of Dermatologists (BAD) 2022 Annual Meeting on July 6.
In April, European Medicines Agency recommended approval of oleogel-S10 for the treatment of partial-thickness skin wounds associated with dystrophic and junctional EB for patients aged 6 months and older.
However, just a month earlier, the U.S. Food and Drug Administration declined to approve the topical agent for use in EB, even after it extended its review by 3 months to include additional analyses of data previously submitted by the company.
In the post-presentation discussion, Dr. Cunningham said that the FDA had “not been satisfied at this point with the information that we have given them,” adding, “We don’t agree with the decision, and we will be appealing.”
Raman K. Madan, MD, a dermatologist at Northwell Health, Huntington, New York, who was not involved in the study, said that the reductions in wound healing seen in the study are “meaningful” and that the numbers represent a “big breakthrough.”
He told this news organization that there are “very few products on the market” for EB and that having an option for patients “would be amazing.”
“The big issue here would be cost and coverage for patients,” he said. If approved, “hopefully” it will be affordable, he added.
Dr. Madan noted that from his perspective, the majority of the reactions to the topical gel were “mild,” and there are “a lot of confounding factors” underlying the number of serious adverse events. “These patients with epidermolysis are prone to some of these issues regardless of treatment,” he said.
During her presentation, Dr. Cunningham noted that EB is a rare, debilitating condition that is characterized by varying degrees of skin fragility, blisters, and impaired wound healing that in turn lead to serious complications that affect quality of life.
While wound management is a “fundamental priority” for patients living with EB, she said, there is a “high, unmet” clinical need.
To those ends, EASE was the largest randomized controlled phase 3 efficacy and safety study in EB. In the study, 252 patients were allocated to receive oleogel-S10 or control gel plus standard-of-care nonadhesive wound dressing.
The double-blind phase of the trial met its primary endpoint: A higher proportion of patients who were given oleogel-S10 achieved first complete closure of the EB target wound by day 45, compared with patients who were given control gel, at 41.3% versus 28.9%. This equated to a relative risk of wound closure by day 45 of 1.44, or an odds ratio of 1.84 (P = .013).
However, as reported at the time by this news organization, the difference in time to wound healing by day 90 between the two patient groups was not statistically significant (P = .302), with 50.5% of oleogel-S10 patients achieving wound closure, versus 43.9% of those in the control group.
Dr. Cunningham discussed the open-label extension, which involved 205 patients from the double-blind phase (mean age, of 16.3 years) treated with oleogel-S10 or control gel plus standard-of-care nonadhesive wound dressing for 24 months.
In presenting the results of the first 12 months of the open-label extension, she said that oleogel-S10 led to “consistent” reductions in the body surface area percentage (BSAP) affected by EB. The overall reduction from baseline was 55% after receiving treatment for 15 months.
Between day 90 and month 12 of the open-label extension, the absolute BSAP was reduced from 7.4% to 5.4% for patients who had received oleogel-S10 from the start of the study. For those who started in the control group and then switched to the oleogel-S10 arm during the open-label extension, the reduction was from 8.3% to 6.4%.
Dr. Cunningham pointed out that a 1% reduction in BSAP equates approximately to the palmar surface of the hand.
Scores on the Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) Skin activity subscale indicated that the reductions achieved in the double-blind phase of the trial were maintained.
Among patients who received oleogel-S10 from the start of the trial, EBDASI Skin scores were reduced from 19.6 at baseline to 13.5 at 12 months’ follow-up in the open-label extension. The reduction was from 19.6 to 13.5 for those who began the trial taking control gel.
Dr. Cunningham showed that adverse events of any grade were seen in 72.0% of patients who began taking oleogel-S10 at the start of the trial and in 69.5% of those who began the trial taking control gel.
Serious adverse events were recorded in 23.0% and 20.0% of patients, respectively, while 6.0% of those who initially received oleogel-S10 and 6.7% of those initially assigned to control gel experienced adverse events that led to study withdrawal during the open-label phase.
The most frequently reported adverse events in the open-label extension were wound complications, seen in 39.5% of patients; anemia, seen in 14.1%; wound infection, seen in 9.3%; pyrexia, seen in 8.3%; and pruritus, seen in 5.9%. No more details regarding adverse events were provided.
The study was funded by Amryt Pharmaceuticals DAC. Dr. Cunningham is an employee of Amryt Pharmaceuticals. No other relevant financial relationships have been disclosed.
A version of this article first appeared on Medscape.com.