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Gestational hypertension-diabetes combo signals CVD risk
Women who develop transient hypertensive disorders during their pregnancy are at risk for developing subsequent cardiovascular disease (CVD), particularly if this experienced at the same time as gestational diabetes.
In a large population-based study, the adjusted hazard ratios for developing CVD following a gestational hypertensive disorder (GHTD) alone were 1.90 (95% confidence interval, 1.151-2.25) within 5 years and 1.41 (95% CI, 1.12-1.76) after 5 years or more.
When gestational diabetes was added into the mix, however, the risk for CVD after 5 years more than doubled (aHR, 2.43; 95% CI, 1.60-3.67). Risk in the earlier postpartum period was also raised by the combination, but this was not significant (aHR, 1.42; 95% CI, 0.78-2.58).
Having gestational diabetes by itself did not seem to increase the risk for later CVD in the analysis, despite being linked to higher heart disease risk in other studies.
“These are women coming out of a pregnancy – young women of reproductive age – so this is not a group that typically has cardiovascular events,” said Ravi Retnakaran, MD, in an interview, an investigator in the new study, which is published in JAMA Network Open.
“If they are somebody who has both disorders concurrently in their pregnancy, they may be at even greater risk than a woman with one or the other disorder,” added Dr. Retnakaran, who is professor of medicine at the University of Toronto and an endocrinologist at the Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, also in Toronto. “In other words, amongst already high-risk patients. This is identifying a subset at maybe an even higher risk.”
It doesn’t mean that there is a huge absolute risk, Dr. Retnakaran said, but it is showing that there is a heightened risk such that women and their clinicians need to be aware of and potentially the need for greater preventative care in the future.
“It is allowing you to identify future lifetime risk of cardiovascular disease,” he said.
Study rationale and design
GHTD is “a forerunner of hypertension,” and gestational diabetes is “a precursor of diabetes” – each associated with a high risk of developing CVD in the years after pregnancy, the investigators said. While studies have looked at their individual contributions to future CVD risk, not many had looked to see what risks having both may confer in the postpregnancy years.
For the analysis, data on 886,295 women with GHTD (43,861), gestational diabetes (54,061), both (4,975), or neither (783,398) were obtained from several Canadian administrative health databases.
The mean age was around 30 years across the groups, with those with both conditions or gestational diabetes alone more likely to be older than those with GTHD alone or neither condition (32 vs. 29 years, respectively, P < .001).
After a total follow-up period of 12 years, 1,999 CVD events were recorded, most of them (1,162) 5 years after the pregnancy.
Pregnancy is a stress test for the heart
“We know that what we call adverse pregnancy outcomes – things like gestational hypertension, and gestational diabetes, and preeclampsia – are on the rise globally,” Natalie A. Bello, MD, director of hypertension research at the Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, commented in an interview.
“People who are younger and of childbearing age who are going into pregnancy now are less healthy than they perhaps were in the past,” Dr. Bello suggested, with more hypertension, more obesity, and people being less physically active. “We think that’s translating into some of the pregnancy complications.”
That’s concerning for a number of reasons, said Dr. Bello, who is also the cochair of the American College of Cardiology’s Cardio-Obstetrics Workgroup, and the biggest one perhaps is the stress that these may conditions may be placing on the heart.
“We know that when individuals have an adverse pregnancy outcome like gestational hypertension, or gestational diabetes, their risk for heart disease is increased in the future compared to someone who has an uncomplicated pregnancy,” she said. “So, we sort of say pregnancy is like a stress test for your heart.”
Dr. Bello added that “these situations, these adverse pregnancy outcomes are an indicator for us as physicians, but also they should be for patients as well, to sort of make sure they’re talking to their doctor about their risk factors and modifying them whenever possible.”
The population studied came from quite a racially, ethnically, and economically diverse area of Canada, Dr. Bello pointed out, although because of the nature of an administrative database there wasn’t information on individual level risk factors.
“We don’t know things like smoking, or if individuals were obese when they were pregnant. So, there are some limitations that should be noted,” she said.
Also, the results don’t mean that isolated gestational diabetes “isn’t something we need to be concerned about,” Dr. Bello observed, adding that the study may have been underpowered to look at this association. “It may just be that it will take a longer time for individuals who have gestational diabetes who don’t make lifestyle changes to develop diabetes, and then develop heart disease.”
The main message is that the women who have a co-occurrence of gestational hypertension and gestational diabetes are at particularly high risk of cardiovascular disease in the future,” said Dr. Retnakaran.
“The way to look at it from a patient standpoint is that we are all on different tracks in terms of our cardiometabolic destiny,” and that these data give “some understanding of what kind of tracks they are on for future risk,” Dr. Retnakaran said.
“A history of either gestational hypertension, and/or gestational diabetes should be really a warning sign for physicians and for patients that they have a higher risk of heart disease,” said Dr. Bello.
She added that this is a signal “that we need to do things to modify their risk, because we know that about 80% of heart disease is modifiable and preventable with proper risk factor management.”
The study was funded by the Ontario Ministry of Health and Long-Term Care. Dr. Retnakaran has received grants and personal fees from Novo Nordisk and Merck, grants from Boehringer Ingelheim, and personal fees from Eli Lily Takeda, and Sanofi. Dr. Bello had no conflicts of interest to disclose.
Women who develop transient hypertensive disorders during their pregnancy are at risk for developing subsequent cardiovascular disease (CVD), particularly if this experienced at the same time as gestational diabetes.
In a large population-based study, the adjusted hazard ratios for developing CVD following a gestational hypertensive disorder (GHTD) alone were 1.90 (95% confidence interval, 1.151-2.25) within 5 years and 1.41 (95% CI, 1.12-1.76) after 5 years or more.
When gestational diabetes was added into the mix, however, the risk for CVD after 5 years more than doubled (aHR, 2.43; 95% CI, 1.60-3.67). Risk in the earlier postpartum period was also raised by the combination, but this was not significant (aHR, 1.42; 95% CI, 0.78-2.58).
Having gestational diabetes by itself did not seem to increase the risk for later CVD in the analysis, despite being linked to higher heart disease risk in other studies.
“These are women coming out of a pregnancy – young women of reproductive age – so this is not a group that typically has cardiovascular events,” said Ravi Retnakaran, MD, in an interview, an investigator in the new study, which is published in JAMA Network Open.
“If they are somebody who has both disorders concurrently in their pregnancy, they may be at even greater risk than a woman with one or the other disorder,” added Dr. Retnakaran, who is professor of medicine at the University of Toronto and an endocrinologist at the Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, also in Toronto. “In other words, amongst already high-risk patients. This is identifying a subset at maybe an even higher risk.”
It doesn’t mean that there is a huge absolute risk, Dr. Retnakaran said, but it is showing that there is a heightened risk such that women and their clinicians need to be aware of and potentially the need for greater preventative care in the future.
“It is allowing you to identify future lifetime risk of cardiovascular disease,” he said.
Study rationale and design
GHTD is “a forerunner of hypertension,” and gestational diabetes is “a precursor of diabetes” – each associated with a high risk of developing CVD in the years after pregnancy, the investigators said. While studies have looked at their individual contributions to future CVD risk, not many had looked to see what risks having both may confer in the postpregnancy years.
For the analysis, data on 886,295 women with GHTD (43,861), gestational diabetes (54,061), both (4,975), or neither (783,398) were obtained from several Canadian administrative health databases.
The mean age was around 30 years across the groups, with those with both conditions or gestational diabetes alone more likely to be older than those with GTHD alone or neither condition (32 vs. 29 years, respectively, P < .001).
After a total follow-up period of 12 years, 1,999 CVD events were recorded, most of them (1,162) 5 years after the pregnancy.
Pregnancy is a stress test for the heart
“We know that what we call adverse pregnancy outcomes – things like gestational hypertension, and gestational diabetes, and preeclampsia – are on the rise globally,” Natalie A. Bello, MD, director of hypertension research at the Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, commented in an interview.
“People who are younger and of childbearing age who are going into pregnancy now are less healthy than they perhaps were in the past,” Dr. Bello suggested, with more hypertension, more obesity, and people being less physically active. “We think that’s translating into some of the pregnancy complications.”
That’s concerning for a number of reasons, said Dr. Bello, who is also the cochair of the American College of Cardiology’s Cardio-Obstetrics Workgroup, and the biggest one perhaps is the stress that these may conditions may be placing on the heart.
“We know that when individuals have an adverse pregnancy outcome like gestational hypertension, or gestational diabetes, their risk for heart disease is increased in the future compared to someone who has an uncomplicated pregnancy,” she said. “So, we sort of say pregnancy is like a stress test for your heart.”
Dr. Bello added that “these situations, these adverse pregnancy outcomes are an indicator for us as physicians, but also they should be for patients as well, to sort of make sure they’re talking to their doctor about their risk factors and modifying them whenever possible.”
The population studied came from quite a racially, ethnically, and economically diverse area of Canada, Dr. Bello pointed out, although because of the nature of an administrative database there wasn’t information on individual level risk factors.
“We don’t know things like smoking, or if individuals were obese when they were pregnant. So, there are some limitations that should be noted,” she said.
Also, the results don’t mean that isolated gestational diabetes “isn’t something we need to be concerned about,” Dr. Bello observed, adding that the study may have been underpowered to look at this association. “It may just be that it will take a longer time for individuals who have gestational diabetes who don’t make lifestyle changes to develop diabetes, and then develop heart disease.”
The main message is that the women who have a co-occurrence of gestational hypertension and gestational diabetes are at particularly high risk of cardiovascular disease in the future,” said Dr. Retnakaran.
“The way to look at it from a patient standpoint is that we are all on different tracks in terms of our cardiometabolic destiny,” and that these data give “some understanding of what kind of tracks they are on for future risk,” Dr. Retnakaran said.
“A history of either gestational hypertension, and/or gestational diabetes should be really a warning sign for physicians and for patients that they have a higher risk of heart disease,” said Dr. Bello.
She added that this is a signal “that we need to do things to modify their risk, because we know that about 80% of heart disease is modifiable and preventable with proper risk factor management.”
The study was funded by the Ontario Ministry of Health and Long-Term Care. Dr. Retnakaran has received grants and personal fees from Novo Nordisk and Merck, grants from Boehringer Ingelheim, and personal fees from Eli Lily Takeda, and Sanofi. Dr. Bello had no conflicts of interest to disclose.
Women who develop transient hypertensive disorders during their pregnancy are at risk for developing subsequent cardiovascular disease (CVD), particularly if this experienced at the same time as gestational diabetes.
In a large population-based study, the adjusted hazard ratios for developing CVD following a gestational hypertensive disorder (GHTD) alone were 1.90 (95% confidence interval, 1.151-2.25) within 5 years and 1.41 (95% CI, 1.12-1.76) after 5 years or more.
When gestational diabetes was added into the mix, however, the risk for CVD after 5 years more than doubled (aHR, 2.43; 95% CI, 1.60-3.67). Risk in the earlier postpartum period was also raised by the combination, but this was not significant (aHR, 1.42; 95% CI, 0.78-2.58).
Having gestational diabetes by itself did not seem to increase the risk for later CVD in the analysis, despite being linked to higher heart disease risk in other studies.
“These are women coming out of a pregnancy – young women of reproductive age – so this is not a group that typically has cardiovascular events,” said Ravi Retnakaran, MD, in an interview, an investigator in the new study, which is published in JAMA Network Open.
“If they are somebody who has both disorders concurrently in their pregnancy, they may be at even greater risk than a woman with one or the other disorder,” added Dr. Retnakaran, who is professor of medicine at the University of Toronto and an endocrinologist at the Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, also in Toronto. “In other words, amongst already high-risk patients. This is identifying a subset at maybe an even higher risk.”
It doesn’t mean that there is a huge absolute risk, Dr. Retnakaran said, but it is showing that there is a heightened risk such that women and their clinicians need to be aware of and potentially the need for greater preventative care in the future.
“It is allowing you to identify future lifetime risk of cardiovascular disease,” he said.
Study rationale and design
GHTD is “a forerunner of hypertension,” and gestational diabetes is “a precursor of diabetes” – each associated with a high risk of developing CVD in the years after pregnancy, the investigators said. While studies have looked at their individual contributions to future CVD risk, not many had looked to see what risks having both may confer in the postpregnancy years.
For the analysis, data on 886,295 women with GHTD (43,861), gestational diabetes (54,061), both (4,975), or neither (783,398) were obtained from several Canadian administrative health databases.
The mean age was around 30 years across the groups, with those with both conditions or gestational diabetes alone more likely to be older than those with GTHD alone or neither condition (32 vs. 29 years, respectively, P < .001).
After a total follow-up period of 12 years, 1,999 CVD events were recorded, most of them (1,162) 5 years after the pregnancy.
Pregnancy is a stress test for the heart
“We know that what we call adverse pregnancy outcomes – things like gestational hypertension, and gestational diabetes, and preeclampsia – are on the rise globally,” Natalie A. Bello, MD, director of hypertension research at the Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, commented in an interview.
“People who are younger and of childbearing age who are going into pregnancy now are less healthy than they perhaps were in the past,” Dr. Bello suggested, with more hypertension, more obesity, and people being less physically active. “We think that’s translating into some of the pregnancy complications.”
That’s concerning for a number of reasons, said Dr. Bello, who is also the cochair of the American College of Cardiology’s Cardio-Obstetrics Workgroup, and the biggest one perhaps is the stress that these may conditions may be placing on the heart.
“We know that when individuals have an adverse pregnancy outcome like gestational hypertension, or gestational diabetes, their risk for heart disease is increased in the future compared to someone who has an uncomplicated pregnancy,” she said. “So, we sort of say pregnancy is like a stress test for your heart.”
Dr. Bello added that “these situations, these adverse pregnancy outcomes are an indicator for us as physicians, but also they should be for patients as well, to sort of make sure they’re talking to their doctor about their risk factors and modifying them whenever possible.”
The population studied came from quite a racially, ethnically, and economically diverse area of Canada, Dr. Bello pointed out, although because of the nature of an administrative database there wasn’t information on individual level risk factors.
“We don’t know things like smoking, or if individuals were obese when they were pregnant. So, there are some limitations that should be noted,” she said.
Also, the results don’t mean that isolated gestational diabetes “isn’t something we need to be concerned about,” Dr. Bello observed, adding that the study may have been underpowered to look at this association. “It may just be that it will take a longer time for individuals who have gestational diabetes who don’t make lifestyle changes to develop diabetes, and then develop heart disease.”
The main message is that the women who have a co-occurrence of gestational hypertension and gestational diabetes are at particularly high risk of cardiovascular disease in the future,” said Dr. Retnakaran.
“The way to look at it from a patient standpoint is that we are all on different tracks in terms of our cardiometabolic destiny,” and that these data give “some understanding of what kind of tracks they are on for future risk,” Dr. Retnakaran said.
“A history of either gestational hypertension, and/or gestational diabetes should be really a warning sign for physicians and for patients that they have a higher risk of heart disease,” said Dr. Bello.
She added that this is a signal “that we need to do things to modify their risk, because we know that about 80% of heart disease is modifiable and preventable with proper risk factor management.”
The study was funded by the Ontario Ministry of Health and Long-Term Care. Dr. Retnakaran has received grants and personal fees from Novo Nordisk and Merck, grants from Boehringer Ingelheim, and personal fees from Eli Lily Takeda, and Sanofi. Dr. Bello had no conflicts of interest to disclose.
FROM JAMA NETWORK OPEN
Higher potency of fentanyl affects addiction treatment, screening
As fentanyl-related overdose deaths continue to increase, clinicians should take note of important differences that set the drug apart from the other drugs of misuse – and the troubling reality that fentanyl now contaminates most of them.
“It would be fair to tell patients, if you’re buying any illicit drugs – pills, powder, liquid, whatever it is, you’ve got to assume it’s either contaminated with or replaced by fentanyl,” said Edwin Salsitz, MD, an associate clinical professor at the Icahn School of Medicine at Mount Sinai, New York, during a presentation on the subject at the 21st Annual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
In many if not most cases, he noted, patients become addicted to fentanyl unknowingly. They assume they are ingesting oxycodone, cocaine, or another drug, and have no realization that they are even exposed to fentanyl until they test positive for it – or overdose.
Meanwhile, the high potency of fentanyl can overcome the opioid blockade of addiction treatment therapies – methadone and buprenorphine – that take away the high that users get from less potent drugs such as heroin.
“Fentanyl is overcoming this blockade that methadone and buprenorphine used to provide,” Dr. Salsitz said. “With fentanyl having such a higher potency, patients are saying ‘no, I still feel the fentanyl effects,’ and they continue feeling it even with 200 milligrams of methadone or 24 milligrams of buprenorphine.”
‘Wooden chest syndrome’
Among the lesser-known dangers of fentanyl is the possibility that some overdose deaths may occur as the result of a syndrome previously reported as a rare complication following the medical use of fentanyl in critically ill patients – fentanyl-induced chest-wall rigidity, or “wooden chest syndrome,” Dr. Salsitz explained.
In such cases, the muscles of respiration become rigid and paralyzed, causing suffocation within a matter of minutes – too soon to benefit from the overdose rescue medication naloxone.
In one recent study published in Clinical Toxicology , nearly half of fentanyl overdose deaths were found to have occurred even before the body had a chance to produce norfentanyl, a metabolite of fentanyl that takes only about 2-3 minutes to appear in the system, suggesting the deaths occurred rapidly.
In the study of 48 fentanyl deaths, no appreciable concentrations of norfentanyl could be detected in 20 of the 48 overdose deaths (42%), and concentrations were less than 1 ng/mL in 25 cases (52%).
“The lack of any measurable norfentanyl in half of our cases suggests a very rapid death, consistent with acute chest rigidity,” the authors reported.
“In several cases fentanyl concentrations were strikingly high (22 ng/mL and 20 ng/mL) with no norfentanyl detected,” they said.
Dr. Salsitz noted that the syndrome is not well known among the addiction treatment community.
“This is different than the usual respiratory opioid overdose where there’s a gradual decrease in the breathing rate and a gradual decrease in how much air is going in and out of the lungs,” Dr. Salsitz explained.
“With those cases, some may survive for an hour or longer, allowing time for someone to administer naloxone or to get the patient to the emergency room,” he said. “But with this, breathing stops and people can die within minutes.
“I think that this is one of the reasons that fentanyl deaths keep going up despite more and more naloxone availability out there,” he said.
Clearance may take longer
In toxicology testing for fentanyl, clinicians should also note the important difference between fentanyl and other opioids – that fentanyl, because of its high lipophilicity, may be detected in urine toxicology testing up to 3 weeks after last use. This is much longer than the 2- to 4-day clearance observed with other opioids, possibly causing patients to continue to test positive for the drug weeks after cessation.
This effect was observed in one recent study of 12 opioid use disorder patients in a residential treatment program who had previously been exposed to daily fentanyl.
The study showed the mean amount of time of fentanyl clearance was 2 weeks, with a range of 4-26 days after last use.
The authors pointed out that the findings “might explain recent reports of difficulty in buprenorphine inductions for persons who use fentanyl, and point to a need to better understand the pharmacokinetics of fentanyl in the context of opioid withdrawal in persons who regularly use fentanyl.”
Though the study was small, Dr. Salsitz said “that’s not a stumbling block to the important finding that, with regular use of fentanyl, the drug may stay in the urine for a long time.”
Dr. Salsitz noted that similar observations have been made at his center, with clinicians logically assuming that patients were still somehow getting fentanyl.
“When we initially found this in patients, we thought that they were using on the unit, perhaps that they brought in the fentanyl, because otherwise how could it stay in the urine that long,” he noted. “But fentanyl appears to be more lipophilic and gets into the fat; it’s then excreted very slowly and then stays in the urine.”
Dr. Salsitz said most practitioners think of fentanyl as a short-acting drug, so “it’s important to realize that people may continue to test positive and it should be thought of as a long-acting opioid.”
Opiate screening tests don’t work
Dr. Salsitz warned of another misconception in fentanyl testing – the common mistake of assuming that fentanyl should show up in a test for opiates – when in fact fentanyl is not, technically, an opiate.
“The word opiate only refers to morphine, codeine, heroin and sometimes hydrocodone,” he explained. “Other opioids are classified as semisynthetic, such as oxycodone, or synthetics, such as fentanyl and methadone, buprenorphine.”
“In order to detect the synthetics, you must have a separate strip for each one of those drugs. They will not show up positive on a screen for opiates,” he noted.
The belief that fentanyl and other synthetic and semisynthetic opioids will show positive on an opiate screen is a common misconception, he said. “The misunderstanding in toxicology interpretation is a problem for many practitioners, [but] it’s essential to understand because otherwise false assumptions about the patient will be considered.”
Another important testing misreading can occur with the antidepressant drug trazodone, which Dr. Salsitz cautioned may falsely test as positive for fentanyl on immunoassays.
“Trazodone is very commonly used in addiction treatment centers, but it can give a false positive on the fentanyl immunoassay and we’ve had a number of those cases,” he said.
Dr. Salsitz had no disclosures to report.
The Psychopharmacology Update was sponsored by Medscape Live. Medscape Live and this news organization are owned by the same parent company.
As fentanyl-related overdose deaths continue to increase, clinicians should take note of important differences that set the drug apart from the other drugs of misuse – and the troubling reality that fentanyl now contaminates most of them.
“It would be fair to tell patients, if you’re buying any illicit drugs – pills, powder, liquid, whatever it is, you’ve got to assume it’s either contaminated with or replaced by fentanyl,” said Edwin Salsitz, MD, an associate clinical professor at the Icahn School of Medicine at Mount Sinai, New York, during a presentation on the subject at the 21st Annual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
In many if not most cases, he noted, patients become addicted to fentanyl unknowingly. They assume they are ingesting oxycodone, cocaine, or another drug, and have no realization that they are even exposed to fentanyl until they test positive for it – or overdose.
Meanwhile, the high potency of fentanyl can overcome the opioid blockade of addiction treatment therapies – methadone and buprenorphine – that take away the high that users get from less potent drugs such as heroin.
“Fentanyl is overcoming this blockade that methadone and buprenorphine used to provide,” Dr. Salsitz said. “With fentanyl having such a higher potency, patients are saying ‘no, I still feel the fentanyl effects,’ and they continue feeling it even with 200 milligrams of methadone or 24 milligrams of buprenorphine.”
‘Wooden chest syndrome’
Among the lesser-known dangers of fentanyl is the possibility that some overdose deaths may occur as the result of a syndrome previously reported as a rare complication following the medical use of fentanyl in critically ill patients – fentanyl-induced chest-wall rigidity, or “wooden chest syndrome,” Dr. Salsitz explained.
In such cases, the muscles of respiration become rigid and paralyzed, causing suffocation within a matter of minutes – too soon to benefit from the overdose rescue medication naloxone.
In one recent study published in Clinical Toxicology , nearly half of fentanyl overdose deaths were found to have occurred even before the body had a chance to produce norfentanyl, a metabolite of fentanyl that takes only about 2-3 minutes to appear in the system, suggesting the deaths occurred rapidly.
In the study of 48 fentanyl deaths, no appreciable concentrations of norfentanyl could be detected in 20 of the 48 overdose deaths (42%), and concentrations were less than 1 ng/mL in 25 cases (52%).
“The lack of any measurable norfentanyl in half of our cases suggests a very rapid death, consistent with acute chest rigidity,” the authors reported.
“In several cases fentanyl concentrations were strikingly high (22 ng/mL and 20 ng/mL) with no norfentanyl detected,” they said.
Dr. Salsitz noted that the syndrome is not well known among the addiction treatment community.
“This is different than the usual respiratory opioid overdose where there’s a gradual decrease in the breathing rate and a gradual decrease in how much air is going in and out of the lungs,” Dr. Salsitz explained.
“With those cases, some may survive for an hour or longer, allowing time for someone to administer naloxone or to get the patient to the emergency room,” he said. “But with this, breathing stops and people can die within minutes.
“I think that this is one of the reasons that fentanyl deaths keep going up despite more and more naloxone availability out there,” he said.
Clearance may take longer
In toxicology testing for fentanyl, clinicians should also note the important difference between fentanyl and other opioids – that fentanyl, because of its high lipophilicity, may be detected in urine toxicology testing up to 3 weeks after last use. This is much longer than the 2- to 4-day clearance observed with other opioids, possibly causing patients to continue to test positive for the drug weeks after cessation.
This effect was observed in one recent study of 12 opioid use disorder patients in a residential treatment program who had previously been exposed to daily fentanyl.
The study showed the mean amount of time of fentanyl clearance was 2 weeks, with a range of 4-26 days after last use.
The authors pointed out that the findings “might explain recent reports of difficulty in buprenorphine inductions for persons who use fentanyl, and point to a need to better understand the pharmacokinetics of fentanyl in the context of opioid withdrawal in persons who regularly use fentanyl.”
Though the study was small, Dr. Salsitz said “that’s not a stumbling block to the important finding that, with regular use of fentanyl, the drug may stay in the urine for a long time.”
Dr. Salsitz noted that similar observations have been made at his center, with clinicians logically assuming that patients were still somehow getting fentanyl.
“When we initially found this in patients, we thought that they were using on the unit, perhaps that they brought in the fentanyl, because otherwise how could it stay in the urine that long,” he noted. “But fentanyl appears to be more lipophilic and gets into the fat; it’s then excreted very slowly and then stays in the urine.”
Dr. Salsitz said most practitioners think of fentanyl as a short-acting drug, so “it’s important to realize that people may continue to test positive and it should be thought of as a long-acting opioid.”
Opiate screening tests don’t work
Dr. Salsitz warned of another misconception in fentanyl testing – the common mistake of assuming that fentanyl should show up in a test for opiates – when in fact fentanyl is not, technically, an opiate.
“The word opiate only refers to morphine, codeine, heroin and sometimes hydrocodone,” he explained. “Other opioids are classified as semisynthetic, such as oxycodone, or synthetics, such as fentanyl and methadone, buprenorphine.”
“In order to detect the synthetics, you must have a separate strip for each one of those drugs. They will not show up positive on a screen for opiates,” he noted.
The belief that fentanyl and other synthetic and semisynthetic opioids will show positive on an opiate screen is a common misconception, he said. “The misunderstanding in toxicology interpretation is a problem for many practitioners, [but] it’s essential to understand because otherwise false assumptions about the patient will be considered.”
Another important testing misreading can occur with the antidepressant drug trazodone, which Dr. Salsitz cautioned may falsely test as positive for fentanyl on immunoassays.
“Trazodone is very commonly used in addiction treatment centers, but it can give a false positive on the fentanyl immunoassay and we’ve had a number of those cases,” he said.
Dr. Salsitz had no disclosures to report.
The Psychopharmacology Update was sponsored by Medscape Live. Medscape Live and this news organization are owned by the same parent company.
As fentanyl-related overdose deaths continue to increase, clinicians should take note of important differences that set the drug apart from the other drugs of misuse – and the troubling reality that fentanyl now contaminates most of them.
“It would be fair to tell patients, if you’re buying any illicit drugs – pills, powder, liquid, whatever it is, you’ve got to assume it’s either contaminated with or replaced by fentanyl,” said Edwin Salsitz, MD, an associate clinical professor at the Icahn School of Medicine at Mount Sinai, New York, during a presentation on the subject at the 21st Annual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
In many if not most cases, he noted, patients become addicted to fentanyl unknowingly. They assume they are ingesting oxycodone, cocaine, or another drug, and have no realization that they are even exposed to fentanyl until they test positive for it – or overdose.
Meanwhile, the high potency of fentanyl can overcome the opioid blockade of addiction treatment therapies – methadone and buprenorphine – that take away the high that users get from less potent drugs such as heroin.
“Fentanyl is overcoming this blockade that methadone and buprenorphine used to provide,” Dr. Salsitz said. “With fentanyl having such a higher potency, patients are saying ‘no, I still feel the fentanyl effects,’ and they continue feeling it even with 200 milligrams of methadone or 24 milligrams of buprenorphine.”
‘Wooden chest syndrome’
Among the lesser-known dangers of fentanyl is the possibility that some overdose deaths may occur as the result of a syndrome previously reported as a rare complication following the medical use of fentanyl in critically ill patients – fentanyl-induced chest-wall rigidity, or “wooden chest syndrome,” Dr. Salsitz explained.
In such cases, the muscles of respiration become rigid and paralyzed, causing suffocation within a matter of minutes – too soon to benefit from the overdose rescue medication naloxone.
In one recent study published in Clinical Toxicology , nearly half of fentanyl overdose deaths were found to have occurred even before the body had a chance to produce norfentanyl, a metabolite of fentanyl that takes only about 2-3 minutes to appear in the system, suggesting the deaths occurred rapidly.
In the study of 48 fentanyl deaths, no appreciable concentrations of norfentanyl could be detected in 20 of the 48 overdose deaths (42%), and concentrations were less than 1 ng/mL in 25 cases (52%).
“The lack of any measurable norfentanyl in half of our cases suggests a very rapid death, consistent with acute chest rigidity,” the authors reported.
“In several cases fentanyl concentrations were strikingly high (22 ng/mL and 20 ng/mL) with no norfentanyl detected,” they said.
Dr. Salsitz noted that the syndrome is not well known among the addiction treatment community.
“This is different than the usual respiratory opioid overdose where there’s a gradual decrease in the breathing rate and a gradual decrease in how much air is going in and out of the lungs,” Dr. Salsitz explained.
“With those cases, some may survive for an hour or longer, allowing time for someone to administer naloxone or to get the patient to the emergency room,” he said. “But with this, breathing stops and people can die within minutes.
“I think that this is one of the reasons that fentanyl deaths keep going up despite more and more naloxone availability out there,” he said.
Clearance may take longer
In toxicology testing for fentanyl, clinicians should also note the important difference between fentanyl and other opioids – that fentanyl, because of its high lipophilicity, may be detected in urine toxicology testing up to 3 weeks after last use. This is much longer than the 2- to 4-day clearance observed with other opioids, possibly causing patients to continue to test positive for the drug weeks after cessation.
This effect was observed in one recent study of 12 opioid use disorder patients in a residential treatment program who had previously been exposed to daily fentanyl.
The study showed the mean amount of time of fentanyl clearance was 2 weeks, with a range of 4-26 days after last use.
The authors pointed out that the findings “might explain recent reports of difficulty in buprenorphine inductions for persons who use fentanyl, and point to a need to better understand the pharmacokinetics of fentanyl in the context of opioid withdrawal in persons who regularly use fentanyl.”
Though the study was small, Dr. Salsitz said “that’s not a stumbling block to the important finding that, with regular use of fentanyl, the drug may stay in the urine for a long time.”
Dr. Salsitz noted that similar observations have been made at his center, with clinicians logically assuming that patients were still somehow getting fentanyl.
“When we initially found this in patients, we thought that they were using on the unit, perhaps that they brought in the fentanyl, because otherwise how could it stay in the urine that long,” he noted. “But fentanyl appears to be more lipophilic and gets into the fat; it’s then excreted very slowly and then stays in the urine.”
Dr. Salsitz said most practitioners think of fentanyl as a short-acting drug, so “it’s important to realize that people may continue to test positive and it should be thought of as a long-acting opioid.”
Opiate screening tests don’t work
Dr. Salsitz warned of another misconception in fentanyl testing – the common mistake of assuming that fentanyl should show up in a test for opiates – when in fact fentanyl is not, technically, an opiate.
“The word opiate only refers to morphine, codeine, heroin and sometimes hydrocodone,” he explained. “Other opioids are classified as semisynthetic, such as oxycodone, or synthetics, such as fentanyl and methadone, buprenorphine.”
“In order to detect the synthetics, you must have a separate strip for each one of those drugs. They will not show up positive on a screen for opiates,” he noted.
The belief that fentanyl and other synthetic and semisynthetic opioids will show positive on an opiate screen is a common misconception, he said. “The misunderstanding in toxicology interpretation is a problem for many practitioners, [but] it’s essential to understand because otherwise false assumptions about the patient will be considered.”
Another important testing misreading can occur with the antidepressant drug trazodone, which Dr. Salsitz cautioned may falsely test as positive for fentanyl on immunoassays.
“Trazodone is very commonly used in addiction treatment centers, but it can give a false positive on the fentanyl immunoassay and we’ve had a number of those cases,” he said.
Dr. Salsitz had no disclosures to report.
The Psychopharmacology Update was sponsored by Medscape Live. Medscape Live and this news organization are owned by the same parent company.
FROM PSYCHOPHARMACOLOGY UPDATE
Managing trastuzumab deruxtecan adverse events in the real world
With recent expansions in its breast cancer indications, there has been an increase in the use of trastuzumab deruxtecan (T-DXd; Enhertu).
“A lot of us are using this more frequently now than we were in the past,” explained Sid Yadav, MD, a breast and gynecologic cancer specialist at the Mayo Clinic in Rochester, Minn. However, he added that managing its adverse events has been a “bit of a learning curve for all of us.”
The antibody-drug conjugate has been on the market since 2019 for metastatic human epidermal growth factor receptor (HER2)–positive breast cancer, but it was then approved in May 2022 for earlier use in this patient population and in August 2022 for patients with HER2-low disease. This latest approval was based on data showing an improvement in overall survival that was described as “practice changing.”
In addition, T-DXd is also approved for use in metastatic HER2-mutated non–small cell lung cancer and metastatic HER2-positive gastric and gastroesophageal junction adenocarcinoma.
, Dr. Yadav told this news organization.
Among the eight or so patients he’s seen or treated over 2 months, Dr. Yadav has already seen one case of high-grade interstitial lung disease/pneumonitis, a complication that “everybody worries about” because the label for T-DXd carries a black box warning of this possibility.
There have been other issues at Mayo Clinic, as well. In one recent week, five patients were admitted for possible T-DXd adverse events, including neutropenic fever and sepsis; pneumonitis; severe nausea/vomiting with electrolyte imbalance; pneumonia, and non–ST elevation myocardial infarction with low ejection fraction.
It’s unknown what proportion of T-DXd recipients the five admissions represented. Dr. Yadav’s service has over 10 breast oncologists, so the cases could represent maybe 1%-10% of patients, he said.
His experience prompted Dr. Yadav to turn to Twitter to ask fellow oncologists what complications they’ve seen with T-DXd.
One said that his “real-world toxicity experience [has been] worse than the trial data,” which isn’t unusual, another oncologist noted, because real-world patients are often sicker than trial participants and more vulnerable to toxicities.
A third oncologist countered that she has “found [T-DXd] generally easy for patients to tolerate and [has] not needed to admit anyone” so far.
Overall, Dr. Yadav said that in his experience there are issues that need to be considered with T-DXd beyond interstitial lung disease.
As with any chemotherapy, neutropenia and infections are a concern, as the labeling notes. The interstitial lung disease case has also made Dr. Yadav have a low threshold to order CT in patients with any hints of shortness of breath and to start steroids if there’s any suspicion.
Probably the most common issue, however, is nausea and vomiting. In clinical trials, over 70% of participants reported nausea and over 40% experienced vomiting.
In response, Dr. Yadav and his colleagues have become more aggressive with prophylaxis. Pretreatment includes steroids, palonosetron, and fosaprepitant. Patients are also usually sent home with prochlorperazine, ondansetron, and lorazepam. If these don’t help, the team considers olanzapine.
They have also learned that “it’s important to spend that extra 15-20 minutes upfront” with patients before starting T-DXd to explain the risk for nausea and vomiting and how it will be managed, Dr. Yadav commented. “We do chemotherapy teaching for every patient, but I think we spend more time [now] talking about nausea and vomiting with this subset,” he said.
Dr. Yadav still starts patients on the standard breast cancer dose of T-DXd – 5.4 mg/kg every 3 weeks – but said he’s quicker now to lower the dose if patients aren’t doing well. He estimates he’s done that a couple of times so far.
Approaches at the Mayo Clinic are in line with those in a recent article on managing T-DXd toxicities by Hope Rugo, MD, from the University of California, San Francisco, and colleagues.
These authors conclude that adverse events related to T-DXd are frequent but are most commonly low grade and manageable. Nausea and vomiting are among the most common, and they note that interstitial lung disease/pneumonitis is an important adverse event, for which proactive monitoring, diagnosis, and management are key.
The review describes management practices of other health care providers and institutions with experience in using T-DXd to help with safe and effective management of the drug’s adverse events, particularly since the duration of treatment may be quite long.
Proper management of T-DXd–related adverse events will allow optimal exposure to and benefit from the drug and will help avoid premature discontinuation or improper dose reductions, Dr. Rugo and colleagues commented.
Dr. Yadav reports no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
With recent expansions in its breast cancer indications, there has been an increase in the use of trastuzumab deruxtecan (T-DXd; Enhertu).
“A lot of us are using this more frequently now than we were in the past,” explained Sid Yadav, MD, a breast and gynecologic cancer specialist at the Mayo Clinic in Rochester, Minn. However, he added that managing its adverse events has been a “bit of a learning curve for all of us.”
The antibody-drug conjugate has been on the market since 2019 for metastatic human epidermal growth factor receptor (HER2)–positive breast cancer, but it was then approved in May 2022 for earlier use in this patient population and in August 2022 for patients with HER2-low disease. This latest approval was based on data showing an improvement in overall survival that was described as “practice changing.”
In addition, T-DXd is also approved for use in metastatic HER2-mutated non–small cell lung cancer and metastatic HER2-positive gastric and gastroesophageal junction adenocarcinoma.
, Dr. Yadav told this news organization.
Among the eight or so patients he’s seen or treated over 2 months, Dr. Yadav has already seen one case of high-grade interstitial lung disease/pneumonitis, a complication that “everybody worries about” because the label for T-DXd carries a black box warning of this possibility.
There have been other issues at Mayo Clinic, as well. In one recent week, five patients were admitted for possible T-DXd adverse events, including neutropenic fever and sepsis; pneumonitis; severe nausea/vomiting with electrolyte imbalance; pneumonia, and non–ST elevation myocardial infarction with low ejection fraction.
It’s unknown what proportion of T-DXd recipients the five admissions represented. Dr. Yadav’s service has over 10 breast oncologists, so the cases could represent maybe 1%-10% of patients, he said.
His experience prompted Dr. Yadav to turn to Twitter to ask fellow oncologists what complications they’ve seen with T-DXd.
One said that his “real-world toxicity experience [has been] worse than the trial data,” which isn’t unusual, another oncologist noted, because real-world patients are often sicker than trial participants and more vulnerable to toxicities.
A third oncologist countered that she has “found [T-DXd] generally easy for patients to tolerate and [has] not needed to admit anyone” so far.
Overall, Dr. Yadav said that in his experience there are issues that need to be considered with T-DXd beyond interstitial lung disease.
As with any chemotherapy, neutropenia and infections are a concern, as the labeling notes. The interstitial lung disease case has also made Dr. Yadav have a low threshold to order CT in patients with any hints of shortness of breath and to start steroids if there’s any suspicion.
Probably the most common issue, however, is nausea and vomiting. In clinical trials, over 70% of participants reported nausea and over 40% experienced vomiting.
In response, Dr. Yadav and his colleagues have become more aggressive with prophylaxis. Pretreatment includes steroids, palonosetron, and fosaprepitant. Patients are also usually sent home with prochlorperazine, ondansetron, and lorazepam. If these don’t help, the team considers olanzapine.
They have also learned that “it’s important to spend that extra 15-20 minutes upfront” with patients before starting T-DXd to explain the risk for nausea and vomiting and how it will be managed, Dr. Yadav commented. “We do chemotherapy teaching for every patient, but I think we spend more time [now] talking about nausea and vomiting with this subset,” he said.
Dr. Yadav still starts patients on the standard breast cancer dose of T-DXd – 5.4 mg/kg every 3 weeks – but said he’s quicker now to lower the dose if patients aren’t doing well. He estimates he’s done that a couple of times so far.
Approaches at the Mayo Clinic are in line with those in a recent article on managing T-DXd toxicities by Hope Rugo, MD, from the University of California, San Francisco, and colleagues.
These authors conclude that adverse events related to T-DXd are frequent but are most commonly low grade and manageable. Nausea and vomiting are among the most common, and they note that interstitial lung disease/pneumonitis is an important adverse event, for which proactive monitoring, diagnosis, and management are key.
The review describes management practices of other health care providers and institutions with experience in using T-DXd to help with safe and effective management of the drug’s adverse events, particularly since the duration of treatment may be quite long.
Proper management of T-DXd–related adverse events will allow optimal exposure to and benefit from the drug and will help avoid premature discontinuation or improper dose reductions, Dr. Rugo and colleagues commented.
Dr. Yadav reports no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
With recent expansions in its breast cancer indications, there has been an increase in the use of trastuzumab deruxtecan (T-DXd; Enhertu).
“A lot of us are using this more frequently now than we were in the past,” explained Sid Yadav, MD, a breast and gynecologic cancer specialist at the Mayo Clinic in Rochester, Minn. However, he added that managing its adverse events has been a “bit of a learning curve for all of us.”
The antibody-drug conjugate has been on the market since 2019 for metastatic human epidermal growth factor receptor (HER2)–positive breast cancer, but it was then approved in May 2022 for earlier use in this patient population and in August 2022 for patients with HER2-low disease. This latest approval was based on data showing an improvement in overall survival that was described as “practice changing.”
In addition, T-DXd is also approved for use in metastatic HER2-mutated non–small cell lung cancer and metastatic HER2-positive gastric and gastroesophageal junction adenocarcinoma.
, Dr. Yadav told this news organization.
Among the eight or so patients he’s seen or treated over 2 months, Dr. Yadav has already seen one case of high-grade interstitial lung disease/pneumonitis, a complication that “everybody worries about” because the label for T-DXd carries a black box warning of this possibility.
There have been other issues at Mayo Clinic, as well. In one recent week, five patients were admitted for possible T-DXd adverse events, including neutropenic fever and sepsis; pneumonitis; severe nausea/vomiting with electrolyte imbalance; pneumonia, and non–ST elevation myocardial infarction with low ejection fraction.
It’s unknown what proportion of T-DXd recipients the five admissions represented. Dr. Yadav’s service has over 10 breast oncologists, so the cases could represent maybe 1%-10% of patients, he said.
His experience prompted Dr. Yadav to turn to Twitter to ask fellow oncologists what complications they’ve seen with T-DXd.
One said that his “real-world toxicity experience [has been] worse than the trial data,” which isn’t unusual, another oncologist noted, because real-world patients are often sicker than trial participants and more vulnerable to toxicities.
A third oncologist countered that she has “found [T-DXd] generally easy for patients to tolerate and [has] not needed to admit anyone” so far.
Overall, Dr. Yadav said that in his experience there are issues that need to be considered with T-DXd beyond interstitial lung disease.
As with any chemotherapy, neutropenia and infections are a concern, as the labeling notes. The interstitial lung disease case has also made Dr. Yadav have a low threshold to order CT in patients with any hints of shortness of breath and to start steroids if there’s any suspicion.
Probably the most common issue, however, is nausea and vomiting. In clinical trials, over 70% of participants reported nausea and over 40% experienced vomiting.
In response, Dr. Yadav and his colleagues have become more aggressive with prophylaxis. Pretreatment includes steroids, palonosetron, and fosaprepitant. Patients are also usually sent home with prochlorperazine, ondansetron, and lorazepam. If these don’t help, the team considers olanzapine.
They have also learned that “it’s important to spend that extra 15-20 minutes upfront” with patients before starting T-DXd to explain the risk for nausea and vomiting and how it will be managed, Dr. Yadav commented. “We do chemotherapy teaching for every patient, but I think we spend more time [now] talking about nausea and vomiting with this subset,” he said.
Dr. Yadav still starts patients on the standard breast cancer dose of T-DXd – 5.4 mg/kg every 3 weeks – but said he’s quicker now to lower the dose if patients aren’t doing well. He estimates he’s done that a couple of times so far.
Approaches at the Mayo Clinic are in line with those in a recent article on managing T-DXd toxicities by Hope Rugo, MD, from the University of California, San Francisco, and colleagues.
These authors conclude that adverse events related to T-DXd are frequent but are most commonly low grade and manageable. Nausea and vomiting are among the most common, and they note that interstitial lung disease/pneumonitis is an important adverse event, for which proactive monitoring, diagnosis, and management are key.
The review describes management practices of other health care providers and institutions with experience in using T-DXd to help with safe and effective management of the drug’s adverse events, particularly since the duration of treatment may be quite long.
Proper management of T-DXd–related adverse events will allow optimal exposure to and benefit from the drug and will help avoid premature discontinuation or improper dose reductions, Dr. Rugo and colleagues commented.
Dr. Yadav reports no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
Lung cancer screening pushes 20-year survival rate to 80%
CHICAGO – , findings from a 20-year international study indicate.
Claudia Henschke, MD, PhD, professor of radiology and director of the Early Lung and Cardiac Action Program at the Icahn School of Medicine at Mount Sinai, New York, presented research results at the annual meeting of the Radiological Society of North America.
The researchers studied lung-cancer–specific survival (LCS) of 87,416 participants enrolled in an international, prospective study named the International Early Lung Cancer Action Program.
Lung cancer is the leading cause of cancer death. The American Lung Association states the average 5-year survival rate is 18.6%. Only 16% of the cancers are caught early and more than half of people with lung cancer die within a year of diagnosis.
Participants’ 20-year survival rate 80%
Results of this large international study showed the overall 20-year survival rate for the 1,285 screening participants diagnosed with early-stage cancer was 80% (95% confidence interval, 77%-83%). Among the 1,285 diagnosed, 83% had stage 1 cancer, Dr. Henschke said.
Lung cancer survival (LCS) was 100% for the 139 participants with nonsolid nodule consistency and for the 155 participants with part-solid consistency. LCS was 73% (95% CI, 69%-77%) for the 991 with solid consistency, and for clinical stage IA participants LCS was 86% (95% CI, 83%-89%), regardless of consistency.
For participants with pathologic stage IA lung cancer 10 mm or less in average diameter, the 20-year survival rate with identification and resection was 92% (95% CI, 87%-96%).
No lung cancer deaths were identified in the part-solid and nonsolid cancers, the researchers report.
These results show the 10-year findings from 2006 published in the New England Journal of Medicine, which also showed 80% survival rates with low-dose CT, have persisted, she said.
At the time of the 2006 paper, 95% of Americans diagnosed with lung cancer died from it, Dr. Henschke said.
Dr. Henschke notes that by the time symptoms appear, lung cancer is often advanced, so the best tool for detecting early-stage lung cancer is enrolling in an annual screening program.
When cancer is small enough and can be surgically removed, patients can be effectively cured long-term, she said.
“In the future, perhaps blood markers will allow us to detect it in the first half of the life cycle of lung cancer instead of CT at the beginning of the second half of the life cycle,” Dr. Henschke said.
“The study raises the power of prospective data collection in the context of clinical care as recommended by the Institute of Medicine long ago,” she said.
Findings “very promising”
Ernest Hawk, MD, MPH, head of the division of cancer prevention and population sciences at the University of Texas MD Anderson Cancer, Houston, told this news organization the findings look “very promising.” Dr. Hawk was not involved in the study.
“This was one of the earliest studies to evaluate low-dose CT scanning. Their report that the initial benefits seem to be holding up over a longer period of observation is great,” he said.
“This bolsters the data that lung cancer screening is beneficial over a longer period of observation,” he said, noting that most of the randomized controlled trials have been shorter.
Lung cancer screening is now recommended for high-risk individuals – those with at least a 20-pack-year history of tobacco use who are between 50 and 80 years old.
So far, screening is still limited to people at high risk, Dr. Hawk said, though there’s discussion about whether benefit would extend to people exposed to asbestos, for instance, or secondhand smoke.
“The biggest challenge right now is getting the screening to those who actually meet the criteria,” Dr. Hawk said.
Medscape reported earlier this month that less than 6% of high-risk smokers have the recommended annual lung cancer screening, according to a new report from the American Lung Association.
Dr. Henschke is on the Advisory Board for LungLifeAI and is on the board for the Early Diagnosis and Treatment Research Foundation. Dr. Hawk reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
CHICAGO – , findings from a 20-year international study indicate.
Claudia Henschke, MD, PhD, professor of radiology and director of the Early Lung and Cardiac Action Program at the Icahn School of Medicine at Mount Sinai, New York, presented research results at the annual meeting of the Radiological Society of North America.
The researchers studied lung-cancer–specific survival (LCS) of 87,416 participants enrolled in an international, prospective study named the International Early Lung Cancer Action Program.
Lung cancer is the leading cause of cancer death. The American Lung Association states the average 5-year survival rate is 18.6%. Only 16% of the cancers are caught early and more than half of people with lung cancer die within a year of diagnosis.
Participants’ 20-year survival rate 80%
Results of this large international study showed the overall 20-year survival rate for the 1,285 screening participants diagnosed with early-stage cancer was 80% (95% confidence interval, 77%-83%). Among the 1,285 diagnosed, 83% had stage 1 cancer, Dr. Henschke said.
Lung cancer survival (LCS) was 100% for the 139 participants with nonsolid nodule consistency and for the 155 participants with part-solid consistency. LCS was 73% (95% CI, 69%-77%) for the 991 with solid consistency, and for clinical stage IA participants LCS was 86% (95% CI, 83%-89%), regardless of consistency.
For participants with pathologic stage IA lung cancer 10 mm or less in average diameter, the 20-year survival rate with identification and resection was 92% (95% CI, 87%-96%).
No lung cancer deaths were identified in the part-solid and nonsolid cancers, the researchers report.
These results show the 10-year findings from 2006 published in the New England Journal of Medicine, which also showed 80% survival rates with low-dose CT, have persisted, she said.
At the time of the 2006 paper, 95% of Americans diagnosed with lung cancer died from it, Dr. Henschke said.
Dr. Henschke notes that by the time symptoms appear, lung cancer is often advanced, so the best tool for detecting early-stage lung cancer is enrolling in an annual screening program.
When cancer is small enough and can be surgically removed, patients can be effectively cured long-term, she said.
“In the future, perhaps blood markers will allow us to detect it in the first half of the life cycle of lung cancer instead of CT at the beginning of the second half of the life cycle,” Dr. Henschke said.
“The study raises the power of prospective data collection in the context of clinical care as recommended by the Institute of Medicine long ago,” she said.
Findings “very promising”
Ernest Hawk, MD, MPH, head of the division of cancer prevention and population sciences at the University of Texas MD Anderson Cancer, Houston, told this news organization the findings look “very promising.” Dr. Hawk was not involved in the study.
“This was one of the earliest studies to evaluate low-dose CT scanning. Their report that the initial benefits seem to be holding up over a longer period of observation is great,” he said.
“This bolsters the data that lung cancer screening is beneficial over a longer period of observation,” he said, noting that most of the randomized controlled trials have been shorter.
Lung cancer screening is now recommended for high-risk individuals – those with at least a 20-pack-year history of tobacco use who are between 50 and 80 years old.
So far, screening is still limited to people at high risk, Dr. Hawk said, though there’s discussion about whether benefit would extend to people exposed to asbestos, for instance, or secondhand smoke.
“The biggest challenge right now is getting the screening to those who actually meet the criteria,” Dr. Hawk said.
Medscape reported earlier this month that less than 6% of high-risk smokers have the recommended annual lung cancer screening, according to a new report from the American Lung Association.
Dr. Henschke is on the Advisory Board for LungLifeAI and is on the board for the Early Diagnosis and Treatment Research Foundation. Dr. Hawk reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
CHICAGO – , findings from a 20-year international study indicate.
Claudia Henschke, MD, PhD, professor of radiology and director of the Early Lung and Cardiac Action Program at the Icahn School of Medicine at Mount Sinai, New York, presented research results at the annual meeting of the Radiological Society of North America.
The researchers studied lung-cancer–specific survival (LCS) of 87,416 participants enrolled in an international, prospective study named the International Early Lung Cancer Action Program.
Lung cancer is the leading cause of cancer death. The American Lung Association states the average 5-year survival rate is 18.6%. Only 16% of the cancers are caught early and more than half of people with lung cancer die within a year of diagnosis.
Participants’ 20-year survival rate 80%
Results of this large international study showed the overall 20-year survival rate for the 1,285 screening participants diagnosed with early-stage cancer was 80% (95% confidence interval, 77%-83%). Among the 1,285 diagnosed, 83% had stage 1 cancer, Dr. Henschke said.
Lung cancer survival (LCS) was 100% for the 139 participants with nonsolid nodule consistency and for the 155 participants with part-solid consistency. LCS was 73% (95% CI, 69%-77%) for the 991 with solid consistency, and for clinical stage IA participants LCS was 86% (95% CI, 83%-89%), regardless of consistency.
For participants with pathologic stage IA lung cancer 10 mm or less in average diameter, the 20-year survival rate with identification and resection was 92% (95% CI, 87%-96%).
No lung cancer deaths were identified in the part-solid and nonsolid cancers, the researchers report.
These results show the 10-year findings from 2006 published in the New England Journal of Medicine, which also showed 80% survival rates with low-dose CT, have persisted, she said.
At the time of the 2006 paper, 95% of Americans diagnosed with lung cancer died from it, Dr. Henschke said.
Dr. Henschke notes that by the time symptoms appear, lung cancer is often advanced, so the best tool for detecting early-stage lung cancer is enrolling in an annual screening program.
When cancer is small enough and can be surgically removed, patients can be effectively cured long-term, she said.
“In the future, perhaps blood markers will allow us to detect it in the first half of the life cycle of lung cancer instead of CT at the beginning of the second half of the life cycle,” Dr. Henschke said.
“The study raises the power of prospective data collection in the context of clinical care as recommended by the Institute of Medicine long ago,” she said.
Findings “very promising”
Ernest Hawk, MD, MPH, head of the division of cancer prevention and population sciences at the University of Texas MD Anderson Cancer, Houston, told this news organization the findings look “very promising.” Dr. Hawk was not involved in the study.
“This was one of the earliest studies to evaluate low-dose CT scanning. Their report that the initial benefits seem to be holding up over a longer period of observation is great,” he said.
“This bolsters the data that lung cancer screening is beneficial over a longer period of observation,” he said, noting that most of the randomized controlled trials have been shorter.
Lung cancer screening is now recommended for high-risk individuals – those with at least a 20-pack-year history of tobacco use who are between 50 and 80 years old.
So far, screening is still limited to people at high risk, Dr. Hawk said, though there’s discussion about whether benefit would extend to people exposed to asbestos, for instance, or secondhand smoke.
“The biggest challenge right now is getting the screening to those who actually meet the criteria,” Dr. Hawk said.
Medscape reported earlier this month that less than 6% of high-risk smokers have the recommended annual lung cancer screening, according to a new report from the American Lung Association.
Dr. Henschke is on the Advisory Board for LungLifeAI and is on the board for the Early Diagnosis and Treatment Research Foundation. Dr. Hawk reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT RSNA 2022
The TikTok trend that triggered a diabetes drug shortage
Weight loss advice is everywhere you look on social media, but one trend sweeping TikTok has led to shortages of an important diabetes drug.
Ozempic, a weekly injection that helps boost insulin sensitivity in people with type 2 diabetes, also suppresses appetite, which leads to weight loss. Stories of celebrities using the drug off-label to lose a few pounds have led to an explosion of interest. And now people with diabetes – people whose lives could be saved by the drug – are having trouble finding it.
Kim Kardashian and Elon Musk
In the spring, Kim Kardashian pulled off a dramatic weight loss to fit into Marilyn Monroe’s dress for the Met Gala. Soon rumors began to circulate that she’d used Ozempic to do it. Just this week, new Twitter owner Elon Musk tweeted about his own use of Ozempic and its sibling drug, Wegovy.
Variety dubbed Ozempic “the worst kept secret in Hollywood – especially given that its most enthusiastic users are not prediabetic and do not require the drug.” The rich and famous are spending $1,200 to $1,500 a month to get access.
As so often happens, high-profile use sparked a trend. Videos on TikTok hashtagged #ozempic have amassed more than 275 million views, and #ozempicweightloss has more than 110 million.
This raises concerns about who, exactly, is watching these videos, and what message they’re receiving.
“Forty-two percent of Americans have obesity, and even more have overweight. That’s affecting our younger people and our adolescents,” says Caroline Apovian, MD, codirector of the Center for Weight Management and Wellness at the Brigham and Women’s Hospital in Boston. “They’re looking at TikTok and other social media outlets for help.”
A new study shows how damaging this can be: Researchers analyzed 1,000 videos with nutrition, food, and weight-related hashtags, with over 1 billion views combined. They found that nearly all included messages glorifying weight loss and thinness.
At last, an effective weight-loss drug
Ozempic is Danish drug company Novo Nordisk’s brand name for semaglutide, which works by mimicking a naturally occurring hormone known as GLP-1. It travels to your brain and helps you feel full on less food. That leads to weight loss. In one 68-week study, semaglutide helped people lose an average of 15% of their body weight. But it’s not a miracle drug: You still have to change your eating habits and stay physically active.
The FDA approved Ozempic to treat people with type 2 diabetes in 2017. Four years later, Novo Nordisk received the green light for a higher-dose version meant specifically for people with obesity. Wegovy is approved for use only if you have a BMI of at least 27 with one or more weight-related ailments, or a BMI of 30 or more with none.
“These drugs are dominating my practice, because they’re so effective,” says Amanda Velazquez, MD, director of obesity medicine at Cedars-Sinai Medical Center in Los Angeles. The drug is considered safe, “so the majority of patients are good candidates.”
More demand than supply
As word spread about how well Ozempic and Wegovy worked, social media posts helped drive even more people to seek out the drugs. Now demand is outpacing the supply – according to the FDA, starter doses of Ozempic will have limited availability through January.
“In Hollywood, people are losing 10 pounds, getting it for $1,500 a month, and depleting stores for people who have such severe obesity that they have congestive heart failure and diabetes,” Dr. Apovian says. “These are people who are going to die, and you’re taking it away just for cosmetic weight loss. That is deplorable.”
In addition to huge demand, Wegovy also had a disruption in its supply chain. Right now, it isn’t available at all in lower doses, which is helping to spike off-label demand for Ozempic. Novo Nordisk expects to have these problems sorted out by the end of the year, with distribution following soon after.
The price of access
With a list price of $1,350 a month, Wegovy costs as much as many mortgages. And Medicaid, Medicare, and many insurance companies don’t cover it. Although obesity is a disease, the insurance industry treats weight loss as more of a vanity issue – so even if you could find the drug, you might not be able to afford it.
“We’re seeing that roughly half the prescriptions we write aren’t being covered,” Dr. Apovian says. “And for the half that are covered, we have to do prior authorization, which takes days, and it’s laborious.” In some instances, she says, insurance companies withdraw authorization after 3 months if they don’t see enough weight coming off.
It’s not like you can take Wegovy for 3 months, lose some weight, and expect it to stay off, either. The medication requires a real commitment, potentially for life. That’s because once the semaglutide leaves your system, your appetite returns. In one study, people regained two-thirds of the weight they’d lost within a year of stopping.
Many see a double standard in the insurance companies’ refusal to cover a drug that could prevent serious illness or death.
“They’re saying it’s not cost-effective to give the 42% of Americans who have a BMI over 30 Wegovy. Did they say this when statins came out?” Dr. Apovian says. “Why are they doing this with antiobesity agents? It’s the culture. The culture isn’t ready to adopt obesity as the disease that it is.”
Unpleasant side effects
Let’s assume you’re one of the lucky ones – your insurance covers Wegovy, and you can actually find some. You might discover that using it is no walk in the park. Common side effects include gastrointestinal issues like nausea, vomiting, and diarrhea.
“The way we counteract that is to start very slowly at a low dose of these medications,” Dr. Apovian says. “We only go up when the patient doesn’t have nausea or it gets better.”
Elise Davenport was excited to try Wegovy. “I did my online research. I’m the type who’s interested in early adoption, tech gadgets and stuff,” says the 40-year-old technical writer. “I wanted to try it because I’d tried so many other things that failed, or hadn’t worked long-term.”
With a BMI over 30, Ms. Davenport qualified for the drug. She signed up for an online program that guaranteed insurance coverage and started taking it in October 2021. At first, the side effects were mild, just a touch of nausea and diarrhea. And the results were impressive. She found it easy to feel satisfied with smaller portions and lost her cravings for sugar and highly processed foods. The weight fell off, roughly 5 pounds a week.
It turns out, that’s too much, too fast. Dr. Apovian and Dr. Velazquez say their patients lose more like 2 pounds each week, with careful monitoring.
By early December, Ms. Davenport’s side effects were ramping up. Because of shortages in lower dosages, the online program wasn’t able to adjust hers right away. She felt nauseated all the time, bad enough that brushing her teeth made her vomit and she had to force herself to eat. Some weeks, she managed less than 500 calories a day. Her sleep patterns became erratic. And then her depression, which medication had kept under control for years, spiraled.
“I remember sitting on the floor of my bathroom crying, thinking I’d rather carry the extra weight,” she says. “I used to take a lot of enjoyment from food, and I had none of that anymore. It was such a joyless experience at that point.”
Eventually, her dosage was reduced and the symptoms let up, but her primary care doctor encouraged her to stop. By the time she did, in March, she’d lost 55 pounds. So far, she’s gained back about 10.
More than just weight loss
Even though Ms. Davenport’s experience wasn’t a good one, with better monitoring, she’d be willing to try again. For one thing, seeing how easy it was to eat less with medical help helped to undo years of shame.
“Our culture treats obesity like a moral failing. I realized I’d been made to feel that way by doctors and programs – that I wasn’t doing enough,” she says. “This drug made me realize there are legit physiological things going on in my body, things that are often excluded from the conversation.”
Dr. Apovian and Dr. Velazquez say their patients regularly discover similar things.
“Obesity is not a disease of willpower. Medications are not the easy way out,” Dr. Velazquez says. “This is a chronic, relapsing medical condition, and because of that, we should treat it how we treat diabetes, high blood pressure, all these other conditions. We’d never hold back medication for individuals coming in with high blood pressure, tell them to work on willpower and withhold drugs they’d qualify for.”
A version of this article first appeared on WebMD.com.
Weight loss advice is everywhere you look on social media, but one trend sweeping TikTok has led to shortages of an important diabetes drug.
Ozempic, a weekly injection that helps boost insulin sensitivity in people with type 2 diabetes, also suppresses appetite, which leads to weight loss. Stories of celebrities using the drug off-label to lose a few pounds have led to an explosion of interest. And now people with diabetes – people whose lives could be saved by the drug – are having trouble finding it.
Kim Kardashian and Elon Musk
In the spring, Kim Kardashian pulled off a dramatic weight loss to fit into Marilyn Monroe’s dress for the Met Gala. Soon rumors began to circulate that she’d used Ozempic to do it. Just this week, new Twitter owner Elon Musk tweeted about his own use of Ozempic and its sibling drug, Wegovy.
Variety dubbed Ozempic “the worst kept secret in Hollywood – especially given that its most enthusiastic users are not prediabetic and do not require the drug.” The rich and famous are spending $1,200 to $1,500 a month to get access.
As so often happens, high-profile use sparked a trend. Videos on TikTok hashtagged #ozempic have amassed more than 275 million views, and #ozempicweightloss has more than 110 million.
This raises concerns about who, exactly, is watching these videos, and what message they’re receiving.
“Forty-two percent of Americans have obesity, and even more have overweight. That’s affecting our younger people and our adolescents,” says Caroline Apovian, MD, codirector of the Center for Weight Management and Wellness at the Brigham and Women’s Hospital in Boston. “They’re looking at TikTok and other social media outlets for help.”
A new study shows how damaging this can be: Researchers analyzed 1,000 videos with nutrition, food, and weight-related hashtags, with over 1 billion views combined. They found that nearly all included messages glorifying weight loss and thinness.
At last, an effective weight-loss drug
Ozempic is Danish drug company Novo Nordisk’s brand name for semaglutide, which works by mimicking a naturally occurring hormone known as GLP-1. It travels to your brain and helps you feel full on less food. That leads to weight loss. In one 68-week study, semaglutide helped people lose an average of 15% of their body weight. But it’s not a miracle drug: You still have to change your eating habits and stay physically active.
The FDA approved Ozempic to treat people with type 2 diabetes in 2017. Four years later, Novo Nordisk received the green light for a higher-dose version meant specifically for people with obesity. Wegovy is approved for use only if you have a BMI of at least 27 with one or more weight-related ailments, or a BMI of 30 or more with none.
“These drugs are dominating my practice, because they’re so effective,” says Amanda Velazquez, MD, director of obesity medicine at Cedars-Sinai Medical Center in Los Angeles. The drug is considered safe, “so the majority of patients are good candidates.”
More demand than supply
As word spread about how well Ozempic and Wegovy worked, social media posts helped drive even more people to seek out the drugs. Now demand is outpacing the supply – according to the FDA, starter doses of Ozempic will have limited availability through January.
“In Hollywood, people are losing 10 pounds, getting it for $1,500 a month, and depleting stores for people who have such severe obesity that they have congestive heart failure and diabetes,” Dr. Apovian says. “These are people who are going to die, and you’re taking it away just for cosmetic weight loss. That is deplorable.”
In addition to huge demand, Wegovy also had a disruption in its supply chain. Right now, it isn’t available at all in lower doses, which is helping to spike off-label demand for Ozempic. Novo Nordisk expects to have these problems sorted out by the end of the year, with distribution following soon after.
The price of access
With a list price of $1,350 a month, Wegovy costs as much as many mortgages. And Medicaid, Medicare, and many insurance companies don’t cover it. Although obesity is a disease, the insurance industry treats weight loss as more of a vanity issue – so even if you could find the drug, you might not be able to afford it.
“We’re seeing that roughly half the prescriptions we write aren’t being covered,” Dr. Apovian says. “And for the half that are covered, we have to do prior authorization, which takes days, and it’s laborious.” In some instances, she says, insurance companies withdraw authorization after 3 months if they don’t see enough weight coming off.
It’s not like you can take Wegovy for 3 months, lose some weight, and expect it to stay off, either. The medication requires a real commitment, potentially for life. That’s because once the semaglutide leaves your system, your appetite returns. In one study, people regained two-thirds of the weight they’d lost within a year of stopping.
Many see a double standard in the insurance companies’ refusal to cover a drug that could prevent serious illness or death.
“They’re saying it’s not cost-effective to give the 42% of Americans who have a BMI over 30 Wegovy. Did they say this when statins came out?” Dr. Apovian says. “Why are they doing this with antiobesity agents? It’s the culture. The culture isn’t ready to adopt obesity as the disease that it is.”
Unpleasant side effects
Let’s assume you’re one of the lucky ones – your insurance covers Wegovy, and you can actually find some. You might discover that using it is no walk in the park. Common side effects include gastrointestinal issues like nausea, vomiting, and diarrhea.
“The way we counteract that is to start very slowly at a low dose of these medications,” Dr. Apovian says. “We only go up when the patient doesn’t have nausea or it gets better.”
Elise Davenport was excited to try Wegovy. “I did my online research. I’m the type who’s interested in early adoption, tech gadgets and stuff,” says the 40-year-old technical writer. “I wanted to try it because I’d tried so many other things that failed, or hadn’t worked long-term.”
With a BMI over 30, Ms. Davenport qualified for the drug. She signed up for an online program that guaranteed insurance coverage and started taking it in October 2021. At first, the side effects were mild, just a touch of nausea and diarrhea. And the results were impressive. She found it easy to feel satisfied with smaller portions and lost her cravings for sugar and highly processed foods. The weight fell off, roughly 5 pounds a week.
It turns out, that’s too much, too fast. Dr. Apovian and Dr. Velazquez say their patients lose more like 2 pounds each week, with careful monitoring.
By early December, Ms. Davenport’s side effects were ramping up. Because of shortages in lower dosages, the online program wasn’t able to adjust hers right away. She felt nauseated all the time, bad enough that brushing her teeth made her vomit and she had to force herself to eat. Some weeks, she managed less than 500 calories a day. Her sleep patterns became erratic. And then her depression, which medication had kept under control for years, spiraled.
“I remember sitting on the floor of my bathroom crying, thinking I’d rather carry the extra weight,” she says. “I used to take a lot of enjoyment from food, and I had none of that anymore. It was such a joyless experience at that point.”
Eventually, her dosage was reduced and the symptoms let up, but her primary care doctor encouraged her to stop. By the time she did, in March, she’d lost 55 pounds. So far, she’s gained back about 10.
More than just weight loss
Even though Ms. Davenport’s experience wasn’t a good one, with better monitoring, she’d be willing to try again. For one thing, seeing how easy it was to eat less with medical help helped to undo years of shame.
“Our culture treats obesity like a moral failing. I realized I’d been made to feel that way by doctors and programs – that I wasn’t doing enough,” she says. “This drug made me realize there are legit physiological things going on in my body, things that are often excluded from the conversation.”
Dr. Apovian and Dr. Velazquez say their patients regularly discover similar things.
“Obesity is not a disease of willpower. Medications are not the easy way out,” Dr. Velazquez says. “This is a chronic, relapsing medical condition, and because of that, we should treat it how we treat diabetes, high blood pressure, all these other conditions. We’d never hold back medication for individuals coming in with high blood pressure, tell them to work on willpower and withhold drugs they’d qualify for.”
A version of this article first appeared on WebMD.com.
Weight loss advice is everywhere you look on social media, but one trend sweeping TikTok has led to shortages of an important diabetes drug.
Ozempic, a weekly injection that helps boost insulin sensitivity in people with type 2 diabetes, also suppresses appetite, which leads to weight loss. Stories of celebrities using the drug off-label to lose a few pounds have led to an explosion of interest. And now people with diabetes – people whose lives could be saved by the drug – are having trouble finding it.
Kim Kardashian and Elon Musk
In the spring, Kim Kardashian pulled off a dramatic weight loss to fit into Marilyn Monroe’s dress for the Met Gala. Soon rumors began to circulate that she’d used Ozempic to do it. Just this week, new Twitter owner Elon Musk tweeted about his own use of Ozempic and its sibling drug, Wegovy.
Variety dubbed Ozempic “the worst kept secret in Hollywood – especially given that its most enthusiastic users are not prediabetic and do not require the drug.” The rich and famous are spending $1,200 to $1,500 a month to get access.
As so often happens, high-profile use sparked a trend. Videos on TikTok hashtagged #ozempic have amassed more than 275 million views, and #ozempicweightloss has more than 110 million.
This raises concerns about who, exactly, is watching these videos, and what message they’re receiving.
“Forty-two percent of Americans have obesity, and even more have overweight. That’s affecting our younger people and our adolescents,” says Caroline Apovian, MD, codirector of the Center for Weight Management and Wellness at the Brigham and Women’s Hospital in Boston. “They’re looking at TikTok and other social media outlets for help.”
A new study shows how damaging this can be: Researchers analyzed 1,000 videos with nutrition, food, and weight-related hashtags, with over 1 billion views combined. They found that nearly all included messages glorifying weight loss and thinness.
At last, an effective weight-loss drug
Ozempic is Danish drug company Novo Nordisk’s brand name for semaglutide, which works by mimicking a naturally occurring hormone known as GLP-1. It travels to your brain and helps you feel full on less food. That leads to weight loss. In one 68-week study, semaglutide helped people lose an average of 15% of their body weight. But it’s not a miracle drug: You still have to change your eating habits and stay physically active.
The FDA approved Ozempic to treat people with type 2 diabetes in 2017. Four years later, Novo Nordisk received the green light for a higher-dose version meant specifically for people with obesity. Wegovy is approved for use only if you have a BMI of at least 27 with one or more weight-related ailments, or a BMI of 30 or more with none.
“These drugs are dominating my practice, because they’re so effective,” says Amanda Velazquez, MD, director of obesity medicine at Cedars-Sinai Medical Center in Los Angeles. The drug is considered safe, “so the majority of patients are good candidates.”
More demand than supply
As word spread about how well Ozempic and Wegovy worked, social media posts helped drive even more people to seek out the drugs. Now demand is outpacing the supply – according to the FDA, starter doses of Ozempic will have limited availability through January.
“In Hollywood, people are losing 10 pounds, getting it for $1,500 a month, and depleting stores for people who have such severe obesity that they have congestive heart failure and diabetes,” Dr. Apovian says. “These are people who are going to die, and you’re taking it away just for cosmetic weight loss. That is deplorable.”
In addition to huge demand, Wegovy also had a disruption in its supply chain. Right now, it isn’t available at all in lower doses, which is helping to spike off-label demand for Ozempic. Novo Nordisk expects to have these problems sorted out by the end of the year, with distribution following soon after.
The price of access
With a list price of $1,350 a month, Wegovy costs as much as many mortgages. And Medicaid, Medicare, and many insurance companies don’t cover it. Although obesity is a disease, the insurance industry treats weight loss as more of a vanity issue – so even if you could find the drug, you might not be able to afford it.
“We’re seeing that roughly half the prescriptions we write aren’t being covered,” Dr. Apovian says. “And for the half that are covered, we have to do prior authorization, which takes days, and it’s laborious.” In some instances, she says, insurance companies withdraw authorization after 3 months if they don’t see enough weight coming off.
It’s not like you can take Wegovy for 3 months, lose some weight, and expect it to stay off, either. The medication requires a real commitment, potentially for life. That’s because once the semaglutide leaves your system, your appetite returns. In one study, people regained two-thirds of the weight they’d lost within a year of stopping.
Many see a double standard in the insurance companies’ refusal to cover a drug that could prevent serious illness or death.
“They’re saying it’s not cost-effective to give the 42% of Americans who have a BMI over 30 Wegovy. Did they say this when statins came out?” Dr. Apovian says. “Why are they doing this with antiobesity agents? It’s the culture. The culture isn’t ready to adopt obesity as the disease that it is.”
Unpleasant side effects
Let’s assume you’re one of the lucky ones – your insurance covers Wegovy, and you can actually find some. You might discover that using it is no walk in the park. Common side effects include gastrointestinal issues like nausea, vomiting, and diarrhea.
“The way we counteract that is to start very slowly at a low dose of these medications,” Dr. Apovian says. “We only go up when the patient doesn’t have nausea or it gets better.”
Elise Davenport was excited to try Wegovy. “I did my online research. I’m the type who’s interested in early adoption, tech gadgets and stuff,” says the 40-year-old technical writer. “I wanted to try it because I’d tried so many other things that failed, or hadn’t worked long-term.”
With a BMI over 30, Ms. Davenport qualified for the drug. She signed up for an online program that guaranteed insurance coverage and started taking it in October 2021. At first, the side effects were mild, just a touch of nausea and diarrhea. And the results were impressive. She found it easy to feel satisfied with smaller portions and lost her cravings for sugar and highly processed foods. The weight fell off, roughly 5 pounds a week.
It turns out, that’s too much, too fast. Dr. Apovian and Dr. Velazquez say their patients lose more like 2 pounds each week, with careful monitoring.
By early December, Ms. Davenport’s side effects were ramping up. Because of shortages in lower dosages, the online program wasn’t able to adjust hers right away. She felt nauseated all the time, bad enough that brushing her teeth made her vomit and she had to force herself to eat. Some weeks, she managed less than 500 calories a day. Her sleep patterns became erratic. And then her depression, which medication had kept under control for years, spiraled.
“I remember sitting on the floor of my bathroom crying, thinking I’d rather carry the extra weight,” she says. “I used to take a lot of enjoyment from food, and I had none of that anymore. It was such a joyless experience at that point.”
Eventually, her dosage was reduced and the symptoms let up, but her primary care doctor encouraged her to stop. By the time she did, in March, she’d lost 55 pounds. So far, she’s gained back about 10.
More than just weight loss
Even though Ms. Davenport’s experience wasn’t a good one, with better monitoring, she’d be willing to try again. For one thing, seeing how easy it was to eat less with medical help helped to undo years of shame.
“Our culture treats obesity like a moral failing. I realized I’d been made to feel that way by doctors and programs – that I wasn’t doing enough,” she says. “This drug made me realize there are legit physiological things going on in my body, things that are often excluded from the conversation.”
Dr. Apovian and Dr. Velazquez say their patients regularly discover similar things.
“Obesity is not a disease of willpower. Medications are not the easy way out,” Dr. Velazquez says. “This is a chronic, relapsing medical condition, and because of that, we should treat it how we treat diabetes, high blood pressure, all these other conditions. We’d never hold back medication for individuals coming in with high blood pressure, tell them to work on willpower and withhold drugs they’d qualify for.”
A version of this article first appeared on WebMD.com.
Both potatoes and beans reduced insulin resistance, weight in controlled study
Low energy–density diets that are based either on potatoes or beans similarly reduced insulin resistance in adults with poor blood glucose control, according to a controlled feeding study in 36 individuals.
Potatoes have gotten a bad rap for their high glycemic index, but they have little fat and a low energy density, wrote the study investigators. In fact, “cooling of gelatinized potatoes generates appreciable levels of slowly digested starch (resistant starch type 3) and substantially lowers the blood glucose response that potatoes elicit.”
“There is a view that potatoes are a less healthy plant food, but there is very little empirical data from randomized trials to support this view,” senior investigator John P. Kirwan, PhD, said in an interview.
Dry beans and peas (known as pulses) also contain resistant starch that improves insulin sensitivity and glucose tolerance, and multiple studies support pulses as part of a low-glycemic diet to improve glucose control in adults, the researchers explained, but because the density of food often guides how much people eat, they hypothesized that potatoes could substitute for beans and provide similar glucose control benefits.
In a study published in the Journal of Medicinal Food, the researchers randomized 36 adults aged 18-60 years with insulin resistance to 8 weeks of a low energy–density diet (1 kcal/g) high in either potatoes or beans. The baseline body mass index ranged from 25 to 40 kg/m2. Insulin resistance was defined using the homeostatic model assessment of insulin resistance (HOMA-IR) with a score greater than 2.
The controlled diet consisted of 50%-55% carbohydrates, 30%-35% fats, and 15%-20% protein. Each meal in the potato group included a side of potatoes, and each meal in the bean group included a side of beans.
The primary outcome was the mean change in blood glucose concentration; the researchers also assessed weight loss.
A total of 14 individuals in the potato group and 17 in the bean group completed the study; but data from the 18 individuals in each group were included in an intent-to-treat analysis.
Among study completers, HOMA-IR in the bean group showed an average decrease of 1.4 from baseline (P = .02 ); a similar decrease of 1.3 occurred in the potato group (P < .05) with no significant difference between the two diets.
Overall compliance with both diets was roughly 88%. Body weight reductions were similar in both groups and significantly reduced from baseline over the study period, with average reductions in intent-to-treat analysis of 5.82 kg in the potato group and 4.0 kg in the bean group. BMI also was significantly reduced from baseline in both potato and bean groups (2.04 kg/m2 and 1.35 kg/m2, respectively). Although baseline differences were not significant, “BMI at baseline was higher and the reduction in response to the treatment was significantly greater in the potato diet compared with the bean diet,” the researchers noted. The effect on blood glucose response was not significantly different between the two groups or from baseline, they said.
The findings were limited by several factors including the small size, relatively short study period, and controlled nature of the study diet, the researchers noted. “The addition of a typical Western diet would have enhanced our understanding of the effect of low energy–dense diets on metabolic outcomes,” they noted in their discussion.
However, both diets led to a reduction in body weight, and the low energy density of both potato and bean diets promoted weight loss without affecting appetite or requiring calorie restriction, the researchers explained. Therefore, “this weight loss if sustained over time could have a substantial impact on body weight,” they said.
“We hypothesized that there would be equivalence between the potato and bean diet and this hypothesis proved to be correct,” said Dr. Kirwan, of the Pennington Biomedical Research Center, Baton Rouge, La., in an interview.
The take-home message for clinicians is that, though small, the study was very well-controlled, Dr. Kirwan emphasized. “Clinicians ought to consider the health benefits of the potato when it is cooked and served appropriately.”
Looking ahead, larger randomized controlled trials with additional control arms, longer time of at least 12 weeks, and different patient populations are needed, Dr. Kirwan added.
Findings mitigate food myths
The debate continues about whether there are foods that are “good” or “evil;” or foods that one “should not eat” or “should eat,” said Amy Rothberg, MD, associate professor of internal medicine and of nutritional sciences at the University of Michigan, Ann Arbor, in an interview.
“This study dispels the myth that incorporating a small portion of potato into the diet (although these are not potatoes that are fried, or are topped with cheese, bacon, sour cream, etc.) results in deleterious metabolic outcomes when compared to a diet that is comprised of beans (pulses) as part of a low energy–dense diet,” she explained.
“The diet in both groups was of low energy density, which has been shown to result in fewer calories consumed, weight loss, and improvement in insulin resistance,” so the similarity in results was not so surprising, said Dr. Rothberg.
For the clinical takeaway, Dr. Rothberg agreed with the study authors: “Clinicians may counsel their patients that they can still consume a small potato (with the caveat above regarding cooking methods and toppings) as part of a balanced meal so long as they are keeping their overall calories low and not exceeding their metabolic requirements based on body weight/BMI,” she said.
As for additional research, studies with a longer time frame and a larger and more diverse study population are needed, including populations with common insulin resistance comorbidities such as type 2 diabetes, fatty liver disease, and cardiovascular disease, Dr. Rothberg noted.
Consumer considerations, with caveats
The key message for consumers is that, “based on this very small study of short duration, consuming a small portion of potato as part of an overall balanced, low-energy diet did not produce adverse effects on glucose or insulin when compared to a diet of pulses known to have favorable effects on glucose and insulin,” Dr. Rothberg told this news organization. However, “consumers should note that, although the results from this small study are encouraging, it would be premature to extrapolate the findings from this study to other populations,” she said. Also, keep in mind that the study was supported in part by the Alliance for Potato Research, although the authors stated that none of the funders (Alliance for Potato Research and Education and the National Institutes of Health) had any role in the design, analysis, or writing of the article, she added.
The study was supported in part by the Alliance for Potato Research and Education and the National Institutes of Health, which funds the Louisiana Clinical and Translational Science Center. The researchers and Dr. Rothberg had no financial conflicts to disclose.
Low energy–density diets that are based either on potatoes or beans similarly reduced insulin resistance in adults with poor blood glucose control, according to a controlled feeding study in 36 individuals.
Potatoes have gotten a bad rap for their high glycemic index, but they have little fat and a low energy density, wrote the study investigators. In fact, “cooling of gelatinized potatoes generates appreciable levels of slowly digested starch (resistant starch type 3) and substantially lowers the blood glucose response that potatoes elicit.”
“There is a view that potatoes are a less healthy plant food, but there is very little empirical data from randomized trials to support this view,” senior investigator John P. Kirwan, PhD, said in an interview.
Dry beans and peas (known as pulses) also contain resistant starch that improves insulin sensitivity and glucose tolerance, and multiple studies support pulses as part of a low-glycemic diet to improve glucose control in adults, the researchers explained, but because the density of food often guides how much people eat, they hypothesized that potatoes could substitute for beans and provide similar glucose control benefits.
In a study published in the Journal of Medicinal Food, the researchers randomized 36 adults aged 18-60 years with insulin resistance to 8 weeks of a low energy–density diet (1 kcal/g) high in either potatoes or beans. The baseline body mass index ranged from 25 to 40 kg/m2. Insulin resistance was defined using the homeostatic model assessment of insulin resistance (HOMA-IR) with a score greater than 2.
The controlled diet consisted of 50%-55% carbohydrates, 30%-35% fats, and 15%-20% protein. Each meal in the potato group included a side of potatoes, and each meal in the bean group included a side of beans.
The primary outcome was the mean change in blood glucose concentration; the researchers also assessed weight loss.
A total of 14 individuals in the potato group and 17 in the bean group completed the study; but data from the 18 individuals in each group were included in an intent-to-treat analysis.
Among study completers, HOMA-IR in the bean group showed an average decrease of 1.4 from baseline (P = .02 ); a similar decrease of 1.3 occurred in the potato group (P < .05) with no significant difference between the two diets.
Overall compliance with both diets was roughly 88%. Body weight reductions were similar in both groups and significantly reduced from baseline over the study period, with average reductions in intent-to-treat analysis of 5.82 kg in the potato group and 4.0 kg in the bean group. BMI also was significantly reduced from baseline in both potato and bean groups (2.04 kg/m2 and 1.35 kg/m2, respectively). Although baseline differences were not significant, “BMI at baseline was higher and the reduction in response to the treatment was significantly greater in the potato diet compared with the bean diet,” the researchers noted. The effect on blood glucose response was not significantly different between the two groups or from baseline, they said.
The findings were limited by several factors including the small size, relatively short study period, and controlled nature of the study diet, the researchers noted. “The addition of a typical Western diet would have enhanced our understanding of the effect of low energy–dense diets on metabolic outcomes,” they noted in their discussion.
However, both diets led to a reduction in body weight, and the low energy density of both potato and bean diets promoted weight loss without affecting appetite or requiring calorie restriction, the researchers explained. Therefore, “this weight loss if sustained over time could have a substantial impact on body weight,” they said.
“We hypothesized that there would be equivalence between the potato and bean diet and this hypothesis proved to be correct,” said Dr. Kirwan, of the Pennington Biomedical Research Center, Baton Rouge, La., in an interview.
The take-home message for clinicians is that, though small, the study was very well-controlled, Dr. Kirwan emphasized. “Clinicians ought to consider the health benefits of the potato when it is cooked and served appropriately.”
Looking ahead, larger randomized controlled trials with additional control arms, longer time of at least 12 weeks, and different patient populations are needed, Dr. Kirwan added.
Findings mitigate food myths
The debate continues about whether there are foods that are “good” or “evil;” or foods that one “should not eat” or “should eat,” said Amy Rothberg, MD, associate professor of internal medicine and of nutritional sciences at the University of Michigan, Ann Arbor, in an interview.
“This study dispels the myth that incorporating a small portion of potato into the diet (although these are not potatoes that are fried, or are topped with cheese, bacon, sour cream, etc.) results in deleterious metabolic outcomes when compared to a diet that is comprised of beans (pulses) as part of a low energy–dense diet,” she explained.
“The diet in both groups was of low energy density, which has been shown to result in fewer calories consumed, weight loss, and improvement in insulin resistance,” so the similarity in results was not so surprising, said Dr. Rothberg.
For the clinical takeaway, Dr. Rothberg agreed with the study authors: “Clinicians may counsel their patients that they can still consume a small potato (with the caveat above regarding cooking methods and toppings) as part of a balanced meal so long as they are keeping their overall calories low and not exceeding their metabolic requirements based on body weight/BMI,” she said.
As for additional research, studies with a longer time frame and a larger and more diverse study population are needed, including populations with common insulin resistance comorbidities such as type 2 diabetes, fatty liver disease, and cardiovascular disease, Dr. Rothberg noted.
Consumer considerations, with caveats
The key message for consumers is that, “based on this very small study of short duration, consuming a small portion of potato as part of an overall balanced, low-energy diet did not produce adverse effects on glucose or insulin when compared to a diet of pulses known to have favorable effects on glucose and insulin,” Dr. Rothberg told this news organization. However, “consumers should note that, although the results from this small study are encouraging, it would be premature to extrapolate the findings from this study to other populations,” she said. Also, keep in mind that the study was supported in part by the Alliance for Potato Research, although the authors stated that none of the funders (Alliance for Potato Research and Education and the National Institutes of Health) had any role in the design, analysis, or writing of the article, she added.
The study was supported in part by the Alliance for Potato Research and Education and the National Institutes of Health, which funds the Louisiana Clinical and Translational Science Center. The researchers and Dr. Rothberg had no financial conflicts to disclose.
Low energy–density diets that are based either on potatoes or beans similarly reduced insulin resistance in adults with poor blood glucose control, according to a controlled feeding study in 36 individuals.
Potatoes have gotten a bad rap for their high glycemic index, but they have little fat and a low energy density, wrote the study investigators. In fact, “cooling of gelatinized potatoes generates appreciable levels of slowly digested starch (resistant starch type 3) and substantially lowers the blood glucose response that potatoes elicit.”
“There is a view that potatoes are a less healthy plant food, but there is very little empirical data from randomized trials to support this view,” senior investigator John P. Kirwan, PhD, said in an interview.
Dry beans and peas (known as pulses) also contain resistant starch that improves insulin sensitivity and glucose tolerance, and multiple studies support pulses as part of a low-glycemic diet to improve glucose control in adults, the researchers explained, but because the density of food often guides how much people eat, they hypothesized that potatoes could substitute for beans and provide similar glucose control benefits.
In a study published in the Journal of Medicinal Food, the researchers randomized 36 adults aged 18-60 years with insulin resistance to 8 weeks of a low energy–density diet (1 kcal/g) high in either potatoes or beans. The baseline body mass index ranged from 25 to 40 kg/m2. Insulin resistance was defined using the homeostatic model assessment of insulin resistance (HOMA-IR) with a score greater than 2.
The controlled diet consisted of 50%-55% carbohydrates, 30%-35% fats, and 15%-20% protein. Each meal in the potato group included a side of potatoes, and each meal in the bean group included a side of beans.
The primary outcome was the mean change in blood glucose concentration; the researchers also assessed weight loss.
A total of 14 individuals in the potato group and 17 in the bean group completed the study; but data from the 18 individuals in each group were included in an intent-to-treat analysis.
Among study completers, HOMA-IR in the bean group showed an average decrease of 1.4 from baseline (P = .02 ); a similar decrease of 1.3 occurred in the potato group (P < .05) with no significant difference between the two diets.
Overall compliance with both diets was roughly 88%. Body weight reductions were similar in both groups and significantly reduced from baseline over the study period, with average reductions in intent-to-treat analysis of 5.82 kg in the potato group and 4.0 kg in the bean group. BMI also was significantly reduced from baseline in both potato and bean groups (2.04 kg/m2 and 1.35 kg/m2, respectively). Although baseline differences were not significant, “BMI at baseline was higher and the reduction in response to the treatment was significantly greater in the potato diet compared with the bean diet,” the researchers noted. The effect on blood glucose response was not significantly different between the two groups or from baseline, they said.
The findings were limited by several factors including the small size, relatively short study period, and controlled nature of the study diet, the researchers noted. “The addition of a typical Western diet would have enhanced our understanding of the effect of low energy–dense diets on metabolic outcomes,” they noted in their discussion.
However, both diets led to a reduction in body weight, and the low energy density of both potato and bean diets promoted weight loss without affecting appetite or requiring calorie restriction, the researchers explained. Therefore, “this weight loss if sustained over time could have a substantial impact on body weight,” they said.
“We hypothesized that there would be equivalence between the potato and bean diet and this hypothesis proved to be correct,” said Dr. Kirwan, of the Pennington Biomedical Research Center, Baton Rouge, La., in an interview.
The take-home message for clinicians is that, though small, the study was very well-controlled, Dr. Kirwan emphasized. “Clinicians ought to consider the health benefits of the potato when it is cooked and served appropriately.”
Looking ahead, larger randomized controlled trials with additional control arms, longer time of at least 12 weeks, and different patient populations are needed, Dr. Kirwan added.
Findings mitigate food myths
The debate continues about whether there are foods that are “good” or “evil;” or foods that one “should not eat” or “should eat,” said Amy Rothberg, MD, associate professor of internal medicine and of nutritional sciences at the University of Michigan, Ann Arbor, in an interview.
“This study dispels the myth that incorporating a small portion of potato into the diet (although these are not potatoes that are fried, or are topped with cheese, bacon, sour cream, etc.) results in deleterious metabolic outcomes when compared to a diet that is comprised of beans (pulses) as part of a low energy–dense diet,” she explained.
“The diet in both groups was of low energy density, which has been shown to result in fewer calories consumed, weight loss, and improvement in insulin resistance,” so the similarity in results was not so surprising, said Dr. Rothberg.
For the clinical takeaway, Dr. Rothberg agreed with the study authors: “Clinicians may counsel their patients that they can still consume a small potato (with the caveat above regarding cooking methods and toppings) as part of a balanced meal so long as they are keeping their overall calories low and not exceeding their metabolic requirements based on body weight/BMI,” she said.
As for additional research, studies with a longer time frame and a larger and more diverse study population are needed, including populations with common insulin resistance comorbidities such as type 2 diabetes, fatty liver disease, and cardiovascular disease, Dr. Rothberg noted.
Consumer considerations, with caveats
The key message for consumers is that, “based on this very small study of short duration, consuming a small portion of potato as part of an overall balanced, low-energy diet did not produce adverse effects on glucose or insulin when compared to a diet of pulses known to have favorable effects on glucose and insulin,” Dr. Rothberg told this news organization. However, “consumers should note that, although the results from this small study are encouraging, it would be premature to extrapolate the findings from this study to other populations,” she said. Also, keep in mind that the study was supported in part by the Alliance for Potato Research, although the authors stated that none of the funders (Alliance for Potato Research and Education and the National Institutes of Health) had any role in the design, analysis, or writing of the article, she added.
The study was supported in part by the Alliance for Potato Research and Education and the National Institutes of Health, which funds the Louisiana Clinical and Translational Science Center. The researchers and Dr. Rothberg had no financial conflicts to disclose.
FROM THE JOURNAL OF MEDICINAL FOOD
Whole breast radiation for breast cancer shown to be safe and effective
The findings from a phase 3 clinical trial are a boon to patient convenience.
“These findings are indeed practice changing. This was a well-designed trial that looked at shortening treatment from 6 weeks down to 3 weeks. And, they showed equivalent local control and importantly, a good cosmetic outcome over time,” said Kathleen Horst, MD, who served as a discussant at a press conference held at the annual meeting of the American Society for Radiation Oncology where the findings were presented.
“This is substantially more convenient. It is cost effective, both for the health care system and for individual patients. Importantly, our patients come in for treatment every day. They’re taking time off of work, they have to arrange for childcare, and they have to arrange for transportation. So this makes a big difference for these patients,” said Dr. Horst, who is a professor of radiation oncology at Stanford (Calif.) Medicine and director of well-being in the radiation department at Stanford Medicine.
The study was presented by Frank A. Vicini, MD, FASTRO, a radiation oncologist with GenesisCare, Farmington Hills, Mich.
“One of the things I think that was surprising is I think all of us were thinking that this might be a more toxic regimen, but as Dr. Vincini showed, over time it was equally effective and with minimal toxicity, and cosmesis over time was stable, and that’s important. Importantly, that included patient-reported outcomes, not just the physician-reported outcomes. Broadly, I think these findings are applicable for many patients, all patients who are receiving whole breast radiotherapy with an added boost. I think over time this is going to improve the quality of life of our patients. It is an innovative change that everyone is going to be excited to embrace,” Dr. Horst said.
Previous randomized, controlled trials showed that an additional radiation dose to the tumor bed following lumpectomy and whole breast irradiation reduces the relative risk of local recurrence by about 35%. However, this increases treatment time for patients who have already endured an extensive regimen. For whole breast irradiation, hypofractionated radiation is in 15-16 fractions over 3 weeks has comparable recurrence rates as a 5-week regimen, but the relevant trials did not examine the effect hypofractionation may have on a radiation boost to the tumor bed of high-risk patients. Because of this lack of evidence, current practice is for the boost to remain sequential in five to eight fractions after completion of whole breast irradiation, which adds a week to a week and a half to treatment length.
The study included 2,262 patients who were randomized to receive a sequential boost or a concomitant boost. After a median follow-up of 7.4 years, there were 54 ipsilateral breast recurrence (IBR) events. The estimated 7-year risk of IBR was 2.2% in the sequential boost and 2.6% in the concurrent risk group (hazard ratio, 1.32; noninferiority test P = .039). Approximately 60% of patients received adjuvant chemotherapy.
Grade 3 or higher adverse events were similar, with a frequency of 3.3% in the sequential group and 3.5% in the concurrent group (P = .79). The researchers used the Global Cosmetic Score to assess outcomes from the perspective of both physicians and patients; 86% of physicians rated the outcome as excellent/good in the sequential group versus 82% in the concurrent group (P = .33).
“For high-risk early-stage breast cancer patients undergoing breast conservation, a concurrent boost with hypofractionated whole breast irradiation as compared to a sequential boost, results in noninferior local recurrence rates with no significant difference in toxicity, noninferior patient-rated cosmesis, no significant difference in physician rated cosmesis, and delivering the entire treatment even at high risk patients in 3 weeks. Just as critical, the use of target volume–based radiation planning for 3-D [three-dimensional] conformal or [intensity-modulated radiation therapy] whole breast irradiation assessed by dose volume analysis is feasible, and resulted in very low toxicity in the treatment arms, regardless of the fractionation schedule, or the boost delivery,” said Dr. Vincini during the press conference.
The study was grant funded. Neither Dr. Vincini nor Dr. Horst had relevant financial disclosures.
The findings from a phase 3 clinical trial are a boon to patient convenience.
“These findings are indeed practice changing. This was a well-designed trial that looked at shortening treatment from 6 weeks down to 3 weeks. And, they showed equivalent local control and importantly, a good cosmetic outcome over time,” said Kathleen Horst, MD, who served as a discussant at a press conference held at the annual meeting of the American Society for Radiation Oncology where the findings were presented.
“This is substantially more convenient. It is cost effective, both for the health care system and for individual patients. Importantly, our patients come in for treatment every day. They’re taking time off of work, they have to arrange for childcare, and they have to arrange for transportation. So this makes a big difference for these patients,” said Dr. Horst, who is a professor of radiation oncology at Stanford (Calif.) Medicine and director of well-being in the radiation department at Stanford Medicine.
The study was presented by Frank A. Vicini, MD, FASTRO, a radiation oncologist with GenesisCare, Farmington Hills, Mich.
“One of the things I think that was surprising is I think all of us were thinking that this might be a more toxic regimen, but as Dr. Vincini showed, over time it was equally effective and with minimal toxicity, and cosmesis over time was stable, and that’s important. Importantly, that included patient-reported outcomes, not just the physician-reported outcomes. Broadly, I think these findings are applicable for many patients, all patients who are receiving whole breast radiotherapy with an added boost. I think over time this is going to improve the quality of life of our patients. It is an innovative change that everyone is going to be excited to embrace,” Dr. Horst said.
Previous randomized, controlled trials showed that an additional radiation dose to the tumor bed following lumpectomy and whole breast irradiation reduces the relative risk of local recurrence by about 35%. However, this increases treatment time for patients who have already endured an extensive regimen. For whole breast irradiation, hypofractionated radiation is in 15-16 fractions over 3 weeks has comparable recurrence rates as a 5-week regimen, but the relevant trials did not examine the effect hypofractionation may have on a radiation boost to the tumor bed of high-risk patients. Because of this lack of evidence, current practice is for the boost to remain sequential in five to eight fractions after completion of whole breast irradiation, which adds a week to a week and a half to treatment length.
The study included 2,262 patients who were randomized to receive a sequential boost or a concomitant boost. After a median follow-up of 7.4 years, there were 54 ipsilateral breast recurrence (IBR) events. The estimated 7-year risk of IBR was 2.2% in the sequential boost and 2.6% in the concurrent risk group (hazard ratio, 1.32; noninferiority test P = .039). Approximately 60% of patients received adjuvant chemotherapy.
Grade 3 or higher adverse events were similar, with a frequency of 3.3% in the sequential group and 3.5% in the concurrent group (P = .79). The researchers used the Global Cosmetic Score to assess outcomes from the perspective of both physicians and patients; 86% of physicians rated the outcome as excellent/good in the sequential group versus 82% in the concurrent group (P = .33).
“For high-risk early-stage breast cancer patients undergoing breast conservation, a concurrent boost with hypofractionated whole breast irradiation as compared to a sequential boost, results in noninferior local recurrence rates with no significant difference in toxicity, noninferior patient-rated cosmesis, no significant difference in physician rated cosmesis, and delivering the entire treatment even at high risk patients in 3 weeks. Just as critical, the use of target volume–based radiation planning for 3-D [three-dimensional] conformal or [intensity-modulated radiation therapy] whole breast irradiation assessed by dose volume analysis is feasible, and resulted in very low toxicity in the treatment arms, regardless of the fractionation schedule, or the boost delivery,” said Dr. Vincini during the press conference.
The study was grant funded. Neither Dr. Vincini nor Dr. Horst had relevant financial disclosures.
The findings from a phase 3 clinical trial are a boon to patient convenience.
“These findings are indeed practice changing. This was a well-designed trial that looked at shortening treatment from 6 weeks down to 3 weeks. And, they showed equivalent local control and importantly, a good cosmetic outcome over time,” said Kathleen Horst, MD, who served as a discussant at a press conference held at the annual meeting of the American Society for Radiation Oncology where the findings were presented.
“This is substantially more convenient. It is cost effective, both for the health care system and for individual patients. Importantly, our patients come in for treatment every day. They’re taking time off of work, they have to arrange for childcare, and they have to arrange for transportation. So this makes a big difference for these patients,” said Dr. Horst, who is a professor of radiation oncology at Stanford (Calif.) Medicine and director of well-being in the radiation department at Stanford Medicine.
The study was presented by Frank A. Vicini, MD, FASTRO, a radiation oncologist with GenesisCare, Farmington Hills, Mich.
“One of the things I think that was surprising is I think all of us were thinking that this might be a more toxic regimen, but as Dr. Vincini showed, over time it was equally effective and with minimal toxicity, and cosmesis over time was stable, and that’s important. Importantly, that included patient-reported outcomes, not just the physician-reported outcomes. Broadly, I think these findings are applicable for many patients, all patients who are receiving whole breast radiotherapy with an added boost. I think over time this is going to improve the quality of life of our patients. It is an innovative change that everyone is going to be excited to embrace,” Dr. Horst said.
Previous randomized, controlled trials showed that an additional radiation dose to the tumor bed following lumpectomy and whole breast irradiation reduces the relative risk of local recurrence by about 35%. However, this increases treatment time for patients who have already endured an extensive regimen. For whole breast irradiation, hypofractionated radiation is in 15-16 fractions over 3 weeks has comparable recurrence rates as a 5-week regimen, but the relevant trials did not examine the effect hypofractionation may have on a radiation boost to the tumor bed of high-risk patients. Because of this lack of evidence, current practice is for the boost to remain sequential in five to eight fractions after completion of whole breast irradiation, which adds a week to a week and a half to treatment length.
The study included 2,262 patients who were randomized to receive a sequential boost or a concomitant boost. After a median follow-up of 7.4 years, there were 54 ipsilateral breast recurrence (IBR) events. The estimated 7-year risk of IBR was 2.2% in the sequential boost and 2.6% in the concurrent risk group (hazard ratio, 1.32; noninferiority test P = .039). Approximately 60% of patients received adjuvant chemotherapy.
Grade 3 or higher adverse events were similar, with a frequency of 3.3% in the sequential group and 3.5% in the concurrent group (P = .79). The researchers used the Global Cosmetic Score to assess outcomes from the perspective of both physicians and patients; 86% of physicians rated the outcome as excellent/good in the sequential group versus 82% in the concurrent group (P = .33).
“For high-risk early-stage breast cancer patients undergoing breast conservation, a concurrent boost with hypofractionated whole breast irradiation as compared to a sequential boost, results in noninferior local recurrence rates with no significant difference in toxicity, noninferior patient-rated cosmesis, no significant difference in physician rated cosmesis, and delivering the entire treatment even at high risk patients in 3 weeks. Just as critical, the use of target volume–based radiation planning for 3-D [three-dimensional] conformal or [intensity-modulated radiation therapy] whole breast irradiation assessed by dose volume analysis is feasible, and resulted in very low toxicity in the treatment arms, regardless of the fractionation schedule, or the boost delivery,” said Dr. Vincini during the press conference.
The study was grant funded. Neither Dr. Vincini nor Dr. Horst had relevant financial disclosures.
FROM ASTRO 2022
New framework for MS diagnosis and treatment proposed
The goal is to eventually move away from the current system, which classifies MS based on disease progression into distinct relapsing-remitting, secondary progressive, and primary progressive subtypes.
Members of the International Advisory Committee on Clinical Trials in Multiple Sclerosis, which developed the framework, note the new framework is based on underlying biology of disease and acknowledges the different trajectories of individual patients. “The categorization of patients into distinct subtypes or stages is artificial,” said framework coauthor Jeffrey Cohen, MD, director of experimental therapeutics, Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic. “The rationale for the new framework was recent studies demonstrating that the biologic processes that underlie relapses and progression are present to varying degrees throughout the disease course, representing a continuum.”
The proposal was published online in The Lancet Neurology.
A more responsive system
Since the current MS classification, dubbed the Lublin-Reingold descriptors, was introduced, there have been calls for a different system that is more responsive to biological changes inherent in MS. The committee, which is jointly sponsored by the European Committee for Treatment and Research in Multiple Sclerosis and the U.S. National Multiple Sclerosis Society, responded by clarifying clinical course descriptions published in 1996 and 2013. The proposed framework grew out of that process.
“One of the main points is the concept that patients don’t evolve into secondary progressive MS,” Dr. Cohen said. “The processes that underlie progression and the findings of proxy measures of progression are present from the earliest stages of the disease.”
In its report, the committee reviews current data on the pathophysiology of injury and compensatory mechanisms in MS, presenting findings that suggest disease progression is caused not by a single disease mechanism, but from a combination of several processes that vary from patient to patient.
Current research studies highlighted in the report include those focused on mechanisms of injury, such as acute and chronic inflammation, myelin loss, nerve fiber and neuron loss, and mitochondrial dysfunction. How the body responds to that injury is likely to determine how MS evolves in each patient, the committee wrote.
Studies point to a range of factors that influence how MS manifests and progresses, including patients’ age at onset, biological sex, genes, race, ethnicity, comorbid health conditions, health behaviors, therapies, and social and environmental exposures.
Potential for better treatments
Any new framework for classifying the disease in the future would enable the development and approval of more biologically based treatment approaches, Dr. Cohen said. “One anticipated advantage of the new framework is that treatments should be evaluated based on their efficacy on biologic processes, not in artificial categories of patients.”
Dr. Cohen and other committee members acknowledged that developing the framework is just a first step in what would likely be a long and complicated process. “This proposal is among many initiatives that the committee has supported over the years as part of its overarching aim to constantly improve, update, and enhance clinical trial design and inform clinical care delivery for people living with MS and their health care teams,” committee chair Ruth Ann Marrie, MD, PhD, director of the Multiple Sclerosis Clinic at the University of Manitoba Health Sciences Center, Winnipeg, said in a press release.
Commenting on the proposal, Tony Reder, MD, professor of neurology at the University of Chicago Medicine, said the paper offers a “good framework for all trialists attempting to go beyond the usual markers.”
The time is right for reclassifying MS
The authors “have good reasons to propose the need for a new mechanism-driven framework to define MS progression,” wrote Takashi Yamamura, MD, PhD, director and chief of the Neuroimmunology Section and director of Multiple Sclerosis Center, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan, in an accompanying commentary.
Adopting biologically based definitions of MS progression will be challenging to implement, the authors admitted. The current subtype classification is woven into clinical care and research models and is the basis for regulatory approval of new therapeutics. Replacing it will take time and require external validation in the clinic and the lab.
“Although the goal is distant and many obstacles might arise (such as reaching a consensus between physicians, academia, and stakeholders), the time seems right to launch initiatives to reframe the classification of MS subtypes,” Dr. Yamamura added.
The study was supported by the German Research Foundation and the Intramural Research Program of NINDS. Dr. Cohen reported personal compensation for consulting for Biogen, Convelo, EMD Serono, Gossamer Bio, Mylan, and PSI. Dr. Yamamura has received support from AMED-CREST, Novartis, and Chiome Bioscience, and speaker honoraria from Novartis, Biogen, Chugai, Alexion, Mitsubishi-Tanabe, and Takeda.
A version of this article first appeared on Medscape.com.
The goal is to eventually move away from the current system, which classifies MS based on disease progression into distinct relapsing-remitting, secondary progressive, and primary progressive subtypes.
Members of the International Advisory Committee on Clinical Trials in Multiple Sclerosis, which developed the framework, note the new framework is based on underlying biology of disease and acknowledges the different trajectories of individual patients. “The categorization of patients into distinct subtypes or stages is artificial,” said framework coauthor Jeffrey Cohen, MD, director of experimental therapeutics, Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic. “The rationale for the new framework was recent studies demonstrating that the biologic processes that underlie relapses and progression are present to varying degrees throughout the disease course, representing a continuum.”
The proposal was published online in The Lancet Neurology.
A more responsive system
Since the current MS classification, dubbed the Lublin-Reingold descriptors, was introduced, there have been calls for a different system that is more responsive to biological changes inherent in MS. The committee, which is jointly sponsored by the European Committee for Treatment and Research in Multiple Sclerosis and the U.S. National Multiple Sclerosis Society, responded by clarifying clinical course descriptions published in 1996 and 2013. The proposed framework grew out of that process.
“One of the main points is the concept that patients don’t evolve into secondary progressive MS,” Dr. Cohen said. “The processes that underlie progression and the findings of proxy measures of progression are present from the earliest stages of the disease.”
In its report, the committee reviews current data on the pathophysiology of injury and compensatory mechanisms in MS, presenting findings that suggest disease progression is caused not by a single disease mechanism, but from a combination of several processes that vary from patient to patient.
Current research studies highlighted in the report include those focused on mechanisms of injury, such as acute and chronic inflammation, myelin loss, nerve fiber and neuron loss, and mitochondrial dysfunction. How the body responds to that injury is likely to determine how MS evolves in each patient, the committee wrote.
Studies point to a range of factors that influence how MS manifests and progresses, including patients’ age at onset, biological sex, genes, race, ethnicity, comorbid health conditions, health behaviors, therapies, and social and environmental exposures.
Potential for better treatments
Any new framework for classifying the disease in the future would enable the development and approval of more biologically based treatment approaches, Dr. Cohen said. “One anticipated advantage of the new framework is that treatments should be evaluated based on their efficacy on biologic processes, not in artificial categories of patients.”
Dr. Cohen and other committee members acknowledged that developing the framework is just a first step in what would likely be a long and complicated process. “This proposal is among many initiatives that the committee has supported over the years as part of its overarching aim to constantly improve, update, and enhance clinical trial design and inform clinical care delivery for people living with MS and their health care teams,” committee chair Ruth Ann Marrie, MD, PhD, director of the Multiple Sclerosis Clinic at the University of Manitoba Health Sciences Center, Winnipeg, said in a press release.
Commenting on the proposal, Tony Reder, MD, professor of neurology at the University of Chicago Medicine, said the paper offers a “good framework for all trialists attempting to go beyond the usual markers.”
The time is right for reclassifying MS
The authors “have good reasons to propose the need for a new mechanism-driven framework to define MS progression,” wrote Takashi Yamamura, MD, PhD, director and chief of the Neuroimmunology Section and director of Multiple Sclerosis Center, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan, in an accompanying commentary.
Adopting biologically based definitions of MS progression will be challenging to implement, the authors admitted. The current subtype classification is woven into clinical care and research models and is the basis for regulatory approval of new therapeutics. Replacing it will take time and require external validation in the clinic and the lab.
“Although the goal is distant and many obstacles might arise (such as reaching a consensus between physicians, academia, and stakeholders), the time seems right to launch initiatives to reframe the classification of MS subtypes,” Dr. Yamamura added.
The study was supported by the German Research Foundation and the Intramural Research Program of NINDS. Dr. Cohen reported personal compensation for consulting for Biogen, Convelo, EMD Serono, Gossamer Bio, Mylan, and PSI. Dr. Yamamura has received support from AMED-CREST, Novartis, and Chiome Bioscience, and speaker honoraria from Novartis, Biogen, Chugai, Alexion, Mitsubishi-Tanabe, and Takeda.
A version of this article first appeared on Medscape.com.
The goal is to eventually move away from the current system, which classifies MS based on disease progression into distinct relapsing-remitting, secondary progressive, and primary progressive subtypes.
Members of the International Advisory Committee on Clinical Trials in Multiple Sclerosis, which developed the framework, note the new framework is based on underlying biology of disease and acknowledges the different trajectories of individual patients. “The categorization of patients into distinct subtypes or stages is artificial,” said framework coauthor Jeffrey Cohen, MD, director of experimental therapeutics, Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic. “The rationale for the new framework was recent studies demonstrating that the biologic processes that underlie relapses and progression are present to varying degrees throughout the disease course, representing a continuum.”
The proposal was published online in The Lancet Neurology.
A more responsive system
Since the current MS classification, dubbed the Lublin-Reingold descriptors, was introduced, there have been calls for a different system that is more responsive to biological changes inherent in MS. The committee, which is jointly sponsored by the European Committee for Treatment and Research in Multiple Sclerosis and the U.S. National Multiple Sclerosis Society, responded by clarifying clinical course descriptions published in 1996 and 2013. The proposed framework grew out of that process.
“One of the main points is the concept that patients don’t evolve into secondary progressive MS,” Dr. Cohen said. “The processes that underlie progression and the findings of proxy measures of progression are present from the earliest stages of the disease.”
In its report, the committee reviews current data on the pathophysiology of injury and compensatory mechanisms in MS, presenting findings that suggest disease progression is caused not by a single disease mechanism, but from a combination of several processes that vary from patient to patient.
Current research studies highlighted in the report include those focused on mechanisms of injury, such as acute and chronic inflammation, myelin loss, nerve fiber and neuron loss, and mitochondrial dysfunction. How the body responds to that injury is likely to determine how MS evolves in each patient, the committee wrote.
Studies point to a range of factors that influence how MS manifests and progresses, including patients’ age at onset, biological sex, genes, race, ethnicity, comorbid health conditions, health behaviors, therapies, and social and environmental exposures.
Potential for better treatments
Any new framework for classifying the disease in the future would enable the development and approval of more biologically based treatment approaches, Dr. Cohen said. “One anticipated advantage of the new framework is that treatments should be evaluated based on their efficacy on biologic processes, not in artificial categories of patients.”
Dr. Cohen and other committee members acknowledged that developing the framework is just a first step in what would likely be a long and complicated process. “This proposal is among many initiatives that the committee has supported over the years as part of its overarching aim to constantly improve, update, and enhance clinical trial design and inform clinical care delivery for people living with MS and their health care teams,” committee chair Ruth Ann Marrie, MD, PhD, director of the Multiple Sclerosis Clinic at the University of Manitoba Health Sciences Center, Winnipeg, said in a press release.
Commenting on the proposal, Tony Reder, MD, professor of neurology at the University of Chicago Medicine, said the paper offers a “good framework for all trialists attempting to go beyond the usual markers.”
The time is right for reclassifying MS
The authors “have good reasons to propose the need for a new mechanism-driven framework to define MS progression,” wrote Takashi Yamamura, MD, PhD, director and chief of the Neuroimmunology Section and director of Multiple Sclerosis Center, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan, in an accompanying commentary.
Adopting biologically based definitions of MS progression will be challenging to implement, the authors admitted. The current subtype classification is woven into clinical care and research models and is the basis for regulatory approval of new therapeutics. Replacing it will take time and require external validation in the clinic and the lab.
“Although the goal is distant and many obstacles might arise (such as reaching a consensus between physicians, academia, and stakeholders), the time seems right to launch initiatives to reframe the classification of MS subtypes,” Dr. Yamamura added.
The study was supported by the German Research Foundation and the Intramural Research Program of NINDS. Dr. Cohen reported personal compensation for consulting for Biogen, Convelo, EMD Serono, Gossamer Bio, Mylan, and PSI. Dr. Yamamura has received support from AMED-CREST, Novartis, and Chiome Bioscience, and speaker honoraria from Novartis, Biogen, Chugai, Alexion, Mitsubishi-Tanabe, and Takeda.
A version of this article first appeared on Medscape.com.
FROM THE LANCET NEUROLOGY
Newer agents for nosocomial pneumonia: The right drug for the right bug
“The right drug at the right time with the right dose for the right bug for the right duration.” That, said professor Kristina Crothers, MD, is the general guidance for optimizing antibiotic use (while awaiting an infectious disease consult). In her oral presentation at the annual meeting of the American College of Chest Physicians, “Choosing newer antibiotics for nosocomial pneumonia,” Dr. Crothers asked the question: “Beyond the guidelines: When should novel antimicrobials be used?”
Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are the most common nosocomial infections at 22%, and are the leading cause of death attributable to hospital-acquired infections. They increase mortality by 20%-50%, with an economic burden of about $40,000 per patient. The incidence of multidrug-resistant (MDR) organism infections varies widely by locality, but several factors increase the likelihood: prior broad-spectrum antibiotic exposure within the past 90 days; longer hospitalization; indwelling vascular devices; tracheostomy; and ventilator dependence. The Centers for Disease Control and Prevention lists as “Serious Threat” the HAP/VAP MDR organisms methicillin resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa (PSA) with difficult-to-treat-resistance, and beta-lactamase producing Enterobacterales (ESBL). In the category of “Urgent Threat” the CDC lists: carbapenamase-resistant Enterobacterales (CRE) (carbapenamase producing or non–carbapenemase producing), and carbapenem-resistant Acinetobacter (CRAB), according to Dr. Crothers who is at the University of Washington Veterans Affairs Puget Sound Health Care System, Seattle.
Newer antibiotics for HAP/VAP that are still beyond the guidelines include telavancin and tedizolid as gram-positive agents, and as gram-negative ones: ceftazidime-avibactam, ceftolozane-tazobactam, cefiderocol, imipenem-cilastatin-relebactam and meropenem-vaborbactam, she added.
Tedizolid, Dr. Crothers stated, is a novel oxazolidinone, and is an alternative to vancomycin and linezolid for gram-positive HAP/VAP. In the VITAL noninferiority study versus linezolid with 726 patients, it was noninferior to linezolid for 28-day all-cause mortality (28% vs. 26%), but did not achieve noninferiority for investigator-assessed clinical cure (56% vs. 64%).
Televancin, a semisynthetic derivative of vancomycin, in the ATTAIN studies vs. vancomycin had overall similar cure rates. It is FDA-approved for S. aureus HAP/VAP but not other bacterial causes. It should be reserved for those who cannot receive vancomycin or linezolid, with normal renal function, according to Dr. Crothers. Excluded from first-line treatment of gram-positive HAP/VAP are daptomycin, ceftaroline, ceftobiprole, and tigecycline.
Ceftazidime-avibactam, a third-generation cephalosporin-plus novel beta-lactamase inhibitor has wide activity (Klebsiella pneumoniae, Enterobacter cloacae, Escherichia coli, Serratia marcescens, Proteus mirabilis, PSA and Haemophilus influenzae. It is also active against some extended-spectrum beta-lactamases (ESBLs), ampC beta-lactamases (AmpCs), and K. pneumoniae carbapenemase (KPC)–producing Enterobacterales, but not with metallo-beta-lactamases). Ceftazidime-avibactam is also indicated for HAP/VAP, and has a toxicity profile including nausea, vomiting, and diarrhea.
In the REPROVE trial of ceftazidime-avibactam vs. meropenem for 7-14 days with 527 clinically evaluable patients (37% K. pneumoniae, 30% P. aeruginosa, and 33%-35% VAP), the clinical cure at 21-25 days post randomization was 69% vs. 73%, respectively, with similar adverse events.
Ceftolozane-tazobactam, a novel fifth-generation cephalosporin plus a beta-lactamase inhibitor has activity against PSA including extensively drug-resistant PSA, AmpC, and ESBL-E, but it has limited activity against Acinetobacter and Stenotrophomonas. It is indicated for HAP/VAP, has reduced efficacy with creatine clearance of 50 mL/min or less, increases transaminases and renal impairment, and causes diarrhea. In ASPECT-NP (n = 726) ceftolozane-tazobactam versus meropenem for 8-14 days (HAP/VAP), showed a 28 day-mortality of 24% vs. 25%, respectively, with test of cure at 54% vs. 53% at 7-14 days post therapy. Adverse events were similar between groups.
Imipenem-cilastatin-relebactam, a novel beta-lactamase inhibitor plus carbapenem, is indicated for HAP/VAP and has activity against ESBL, CRE: KPC-producing Enterobacterales, PSA including AmpC. It can cause seizures (requires caution with central nervous system disorders and renal impairment). It increases transaminases, anemia, diarrhea, and reduces potassium and sodium. In RESTORE-IMI 2 (n = 537 with HAP/VAP) it was noninferior for 28-day all-cause mortality vs. piperacillin and tazobactam (16% vs. 21%), with similar adverse events.
Cefiderocol, a siderophore cephalosporin, is indicated for HAP/VAP. It has a wide spectrum of activity: ESBL, CRE, CR PSA, Stenotrophomonas maltophilia, Acinetobacter baumanii, Streptococcus.) It increases transaminases, diarrhea, and atrial fibrillation, and it reduces potassium and magnesium. In APEKS-NP versus linezolid plus cefiderocol or extended meropenem infusion (HAP/VAP n = 292; gram-negative pneumonia = 251; 60% invasive mechanical ventilation) it was noninferior for 14-day all-cause mortality (12.4% vs. 11.6%) with similar adverse events. In CREDIBLE-CR vs. best available therapy for carbapenem-resistant gram-negative infections, clinical cure rates were similar (50% vs. 53% in 59 HAP/VAP patients at 7 days), but with more deaths in the cefiderocol arm. Adverse events were > 90% in both groups and 34% vs. 19% died, mostly with Acinetobacter.
Meropenem-vaborbactam, a novel beta-lactamase inhibitor plus carbapenem, is approved and indicated for HAP/VAP in Europe. It has activity against MDR, Enterobacterales including CRE. Its toxicities include headache, phlebitis/infusion-site reactions and diarrhea. In TANGO-2 versus best available treatment for carbapenem-resistant Enterobacteriaceae (CRE) (n = 77, 47 with confirmed CRE), clinical cure was increased and mortality decreased compared with best available therapy. Treatment- and renal-related adverse events were lower for meropenem-vaborbactam.
In closing, Dr. Crothers cited advice from the paper by Tamma et al. (“Rethinking how Antibiotics are Prescribed” JAMA. 2018) about the need to review findings after therapy has been initiated to confirm the pneumonia diagnosis: Novel agents should be kept in reserve in the absence of MDR risk factors for MRSA and gram-negative bacilli; therapy should be deescalated after 48-72 hours if MDR organisms are not detected; and therapy should be directed to the specific organism detected. Most HAP and VAP in adults can be treated for 7 days, she added.
“Know indications for new therapeutic agents approved for nosocomial pneumonia,” she concluded.
Dr. Crothers reported having no disclosures.
“The right drug at the right time with the right dose for the right bug for the right duration.” That, said professor Kristina Crothers, MD, is the general guidance for optimizing antibiotic use (while awaiting an infectious disease consult). In her oral presentation at the annual meeting of the American College of Chest Physicians, “Choosing newer antibiotics for nosocomial pneumonia,” Dr. Crothers asked the question: “Beyond the guidelines: When should novel antimicrobials be used?”
Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are the most common nosocomial infections at 22%, and are the leading cause of death attributable to hospital-acquired infections. They increase mortality by 20%-50%, with an economic burden of about $40,000 per patient. The incidence of multidrug-resistant (MDR) organism infections varies widely by locality, but several factors increase the likelihood: prior broad-spectrum antibiotic exposure within the past 90 days; longer hospitalization; indwelling vascular devices; tracheostomy; and ventilator dependence. The Centers for Disease Control and Prevention lists as “Serious Threat” the HAP/VAP MDR organisms methicillin resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa (PSA) with difficult-to-treat-resistance, and beta-lactamase producing Enterobacterales (ESBL). In the category of “Urgent Threat” the CDC lists: carbapenamase-resistant Enterobacterales (CRE) (carbapenamase producing or non–carbapenemase producing), and carbapenem-resistant Acinetobacter (CRAB), according to Dr. Crothers who is at the University of Washington Veterans Affairs Puget Sound Health Care System, Seattle.
Newer antibiotics for HAP/VAP that are still beyond the guidelines include telavancin and tedizolid as gram-positive agents, and as gram-negative ones: ceftazidime-avibactam, ceftolozane-tazobactam, cefiderocol, imipenem-cilastatin-relebactam and meropenem-vaborbactam, she added.
Tedizolid, Dr. Crothers stated, is a novel oxazolidinone, and is an alternative to vancomycin and linezolid for gram-positive HAP/VAP. In the VITAL noninferiority study versus linezolid with 726 patients, it was noninferior to linezolid for 28-day all-cause mortality (28% vs. 26%), but did not achieve noninferiority for investigator-assessed clinical cure (56% vs. 64%).
Televancin, a semisynthetic derivative of vancomycin, in the ATTAIN studies vs. vancomycin had overall similar cure rates. It is FDA-approved for S. aureus HAP/VAP but not other bacterial causes. It should be reserved for those who cannot receive vancomycin or linezolid, with normal renal function, according to Dr. Crothers. Excluded from first-line treatment of gram-positive HAP/VAP are daptomycin, ceftaroline, ceftobiprole, and tigecycline.
Ceftazidime-avibactam, a third-generation cephalosporin-plus novel beta-lactamase inhibitor has wide activity (Klebsiella pneumoniae, Enterobacter cloacae, Escherichia coli, Serratia marcescens, Proteus mirabilis, PSA and Haemophilus influenzae. It is also active against some extended-spectrum beta-lactamases (ESBLs), ampC beta-lactamases (AmpCs), and K. pneumoniae carbapenemase (KPC)–producing Enterobacterales, but not with metallo-beta-lactamases). Ceftazidime-avibactam is also indicated for HAP/VAP, and has a toxicity profile including nausea, vomiting, and diarrhea.
In the REPROVE trial of ceftazidime-avibactam vs. meropenem for 7-14 days with 527 clinically evaluable patients (37% K. pneumoniae, 30% P. aeruginosa, and 33%-35% VAP), the clinical cure at 21-25 days post randomization was 69% vs. 73%, respectively, with similar adverse events.
Ceftolozane-tazobactam, a novel fifth-generation cephalosporin plus a beta-lactamase inhibitor has activity against PSA including extensively drug-resistant PSA, AmpC, and ESBL-E, but it has limited activity against Acinetobacter and Stenotrophomonas. It is indicated for HAP/VAP, has reduced efficacy with creatine clearance of 50 mL/min or less, increases transaminases and renal impairment, and causes diarrhea. In ASPECT-NP (n = 726) ceftolozane-tazobactam versus meropenem for 8-14 days (HAP/VAP), showed a 28 day-mortality of 24% vs. 25%, respectively, with test of cure at 54% vs. 53% at 7-14 days post therapy. Adverse events were similar between groups.
Imipenem-cilastatin-relebactam, a novel beta-lactamase inhibitor plus carbapenem, is indicated for HAP/VAP and has activity against ESBL, CRE: KPC-producing Enterobacterales, PSA including AmpC. It can cause seizures (requires caution with central nervous system disorders and renal impairment). It increases transaminases, anemia, diarrhea, and reduces potassium and sodium. In RESTORE-IMI 2 (n = 537 with HAP/VAP) it was noninferior for 28-day all-cause mortality vs. piperacillin and tazobactam (16% vs. 21%), with similar adverse events.
Cefiderocol, a siderophore cephalosporin, is indicated for HAP/VAP. It has a wide spectrum of activity: ESBL, CRE, CR PSA, Stenotrophomonas maltophilia, Acinetobacter baumanii, Streptococcus.) It increases transaminases, diarrhea, and atrial fibrillation, and it reduces potassium and magnesium. In APEKS-NP versus linezolid plus cefiderocol or extended meropenem infusion (HAP/VAP n = 292; gram-negative pneumonia = 251; 60% invasive mechanical ventilation) it was noninferior for 14-day all-cause mortality (12.4% vs. 11.6%) with similar adverse events. In CREDIBLE-CR vs. best available therapy for carbapenem-resistant gram-negative infections, clinical cure rates were similar (50% vs. 53% in 59 HAP/VAP patients at 7 days), but with more deaths in the cefiderocol arm. Adverse events were > 90% in both groups and 34% vs. 19% died, mostly with Acinetobacter.
Meropenem-vaborbactam, a novel beta-lactamase inhibitor plus carbapenem, is approved and indicated for HAP/VAP in Europe. It has activity against MDR, Enterobacterales including CRE. Its toxicities include headache, phlebitis/infusion-site reactions and diarrhea. In TANGO-2 versus best available treatment for carbapenem-resistant Enterobacteriaceae (CRE) (n = 77, 47 with confirmed CRE), clinical cure was increased and mortality decreased compared with best available therapy. Treatment- and renal-related adverse events were lower for meropenem-vaborbactam.
In closing, Dr. Crothers cited advice from the paper by Tamma et al. (“Rethinking how Antibiotics are Prescribed” JAMA. 2018) about the need to review findings after therapy has been initiated to confirm the pneumonia diagnosis: Novel agents should be kept in reserve in the absence of MDR risk factors for MRSA and gram-negative bacilli; therapy should be deescalated after 48-72 hours if MDR organisms are not detected; and therapy should be directed to the specific organism detected. Most HAP and VAP in adults can be treated for 7 days, she added.
“Know indications for new therapeutic agents approved for nosocomial pneumonia,” she concluded.
Dr. Crothers reported having no disclosures.
“The right drug at the right time with the right dose for the right bug for the right duration.” That, said professor Kristina Crothers, MD, is the general guidance for optimizing antibiotic use (while awaiting an infectious disease consult). In her oral presentation at the annual meeting of the American College of Chest Physicians, “Choosing newer antibiotics for nosocomial pneumonia,” Dr. Crothers asked the question: “Beyond the guidelines: When should novel antimicrobials be used?”
Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are the most common nosocomial infections at 22%, and are the leading cause of death attributable to hospital-acquired infections. They increase mortality by 20%-50%, with an economic burden of about $40,000 per patient. The incidence of multidrug-resistant (MDR) organism infections varies widely by locality, but several factors increase the likelihood: prior broad-spectrum antibiotic exposure within the past 90 days; longer hospitalization; indwelling vascular devices; tracheostomy; and ventilator dependence. The Centers for Disease Control and Prevention lists as “Serious Threat” the HAP/VAP MDR organisms methicillin resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa (PSA) with difficult-to-treat-resistance, and beta-lactamase producing Enterobacterales (ESBL). In the category of “Urgent Threat” the CDC lists: carbapenamase-resistant Enterobacterales (CRE) (carbapenamase producing or non–carbapenemase producing), and carbapenem-resistant Acinetobacter (CRAB), according to Dr. Crothers who is at the University of Washington Veterans Affairs Puget Sound Health Care System, Seattle.
Newer antibiotics for HAP/VAP that are still beyond the guidelines include telavancin and tedizolid as gram-positive agents, and as gram-negative ones: ceftazidime-avibactam, ceftolozane-tazobactam, cefiderocol, imipenem-cilastatin-relebactam and meropenem-vaborbactam, she added.
Tedizolid, Dr. Crothers stated, is a novel oxazolidinone, and is an alternative to vancomycin and linezolid for gram-positive HAP/VAP. In the VITAL noninferiority study versus linezolid with 726 patients, it was noninferior to linezolid for 28-day all-cause mortality (28% vs. 26%), but did not achieve noninferiority for investigator-assessed clinical cure (56% vs. 64%).
Televancin, a semisynthetic derivative of vancomycin, in the ATTAIN studies vs. vancomycin had overall similar cure rates. It is FDA-approved for S. aureus HAP/VAP but not other bacterial causes. It should be reserved for those who cannot receive vancomycin or linezolid, with normal renal function, according to Dr. Crothers. Excluded from first-line treatment of gram-positive HAP/VAP are daptomycin, ceftaroline, ceftobiprole, and tigecycline.
Ceftazidime-avibactam, a third-generation cephalosporin-plus novel beta-lactamase inhibitor has wide activity (Klebsiella pneumoniae, Enterobacter cloacae, Escherichia coli, Serratia marcescens, Proteus mirabilis, PSA and Haemophilus influenzae. It is also active against some extended-spectrum beta-lactamases (ESBLs), ampC beta-lactamases (AmpCs), and K. pneumoniae carbapenemase (KPC)–producing Enterobacterales, but not with metallo-beta-lactamases). Ceftazidime-avibactam is also indicated for HAP/VAP, and has a toxicity profile including nausea, vomiting, and diarrhea.
In the REPROVE trial of ceftazidime-avibactam vs. meropenem for 7-14 days with 527 clinically evaluable patients (37% K. pneumoniae, 30% P. aeruginosa, and 33%-35% VAP), the clinical cure at 21-25 days post randomization was 69% vs. 73%, respectively, with similar adverse events.
Ceftolozane-tazobactam, a novel fifth-generation cephalosporin plus a beta-lactamase inhibitor has activity against PSA including extensively drug-resistant PSA, AmpC, and ESBL-E, but it has limited activity against Acinetobacter and Stenotrophomonas. It is indicated for HAP/VAP, has reduced efficacy with creatine clearance of 50 mL/min or less, increases transaminases and renal impairment, and causes diarrhea. In ASPECT-NP (n = 726) ceftolozane-tazobactam versus meropenem for 8-14 days (HAP/VAP), showed a 28 day-mortality of 24% vs. 25%, respectively, with test of cure at 54% vs. 53% at 7-14 days post therapy. Adverse events were similar between groups.
Imipenem-cilastatin-relebactam, a novel beta-lactamase inhibitor plus carbapenem, is indicated for HAP/VAP and has activity against ESBL, CRE: KPC-producing Enterobacterales, PSA including AmpC. It can cause seizures (requires caution with central nervous system disorders and renal impairment). It increases transaminases, anemia, diarrhea, and reduces potassium and sodium. In RESTORE-IMI 2 (n = 537 with HAP/VAP) it was noninferior for 28-day all-cause mortality vs. piperacillin and tazobactam (16% vs. 21%), with similar adverse events.
Cefiderocol, a siderophore cephalosporin, is indicated for HAP/VAP. It has a wide spectrum of activity: ESBL, CRE, CR PSA, Stenotrophomonas maltophilia, Acinetobacter baumanii, Streptococcus.) It increases transaminases, diarrhea, and atrial fibrillation, and it reduces potassium and magnesium. In APEKS-NP versus linezolid plus cefiderocol or extended meropenem infusion (HAP/VAP n = 292; gram-negative pneumonia = 251; 60% invasive mechanical ventilation) it was noninferior for 14-day all-cause mortality (12.4% vs. 11.6%) with similar adverse events. In CREDIBLE-CR vs. best available therapy for carbapenem-resistant gram-negative infections, clinical cure rates were similar (50% vs. 53% in 59 HAP/VAP patients at 7 days), but with more deaths in the cefiderocol arm. Adverse events were > 90% in both groups and 34% vs. 19% died, mostly with Acinetobacter.
Meropenem-vaborbactam, a novel beta-lactamase inhibitor plus carbapenem, is approved and indicated for HAP/VAP in Europe. It has activity against MDR, Enterobacterales including CRE. Its toxicities include headache, phlebitis/infusion-site reactions and diarrhea. In TANGO-2 versus best available treatment for carbapenem-resistant Enterobacteriaceae (CRE) (n = 77, 47 with confirmed CRE), clinical cure was increased and mortality decreased compared with best available therapy. Treatment- and renal-related adverse events were lower for meropenem-vaborbactam.
In closing, Dr. Crothers cited advice from the paper by Tamma et al. (“Rethinking how Antibiotics are Prescribed” JAMA. 2018) about the need to review findings after therapy has been initiated to confirm the pneumonia diagnosis: Novel agents should be kept in reserve in the absence of MDR risk factors for MRSA and gram-negative bacilli; therapy should be deescalated after 48-72 hours if MDR organisms are not detected; and therapy should be directed to the specific organism detected. Most HAP and VAP in adults can be treated for 7 days, she added.
“Know indications for new therapeutic agents approved for nosocomial pneumonia,” she concluded.
Dr. Crothers reported having no disclosures.
FROM CHEST 2022
Migraine in children and teens: managing the pain
By the time Mira Halker started high school, hardly a day passed that she wasn’t either getting a migraine attack or recovering from one. She missed volleyball team practice. She missed classes. She missed social events. And few people understood. After all, she looked healthy.
“A lot of times, people think I’m faking it,” said Mira, now 16, who lives in Phoenix. Friends called her flaky; her volleyball coaches questioned her dedication to the team. “I’m like, ‘I’m not trying to get out of this. This is not what this is about,’ ” she said.
Her mother, Rashmi B. Halker Singh, MD, is a neurologist at Mayo Clinic who happens to specialize in migraine. Even so, finding a solution was not easy. Neither ibuprofen nor triptans, nor various preventive measures such as a daily prescription for topiramate controlled the pain and associated symptoms. Mira was barely making it through her school day and had to quit volleyball. Then, in the spring of 10th grade, Mira told her mother that she couldn’t go to prom because the loud noises and lights could give her a migraine attack.
Mother and daughter decided it was time to get even more aggressive. “There are these key moments in life that you can’t get back,” Dr. Singh said. “Migraine steals so much from you.”
Diagnosis
One of the challenges Mira’s physicians faced was deciding which medications and other therapies to prescribe to a teenager. Drug companies have been releasing a steady stream of new treatments for migraine headaches, and researchers promise more are on the way soon. Here’s what works for children, what hasn’t yet been approved for use with minors, and how to diagnose migraines in the first place, from experts at some of the nation’s leading pediatric headache centers.
Migraine affects about 10% of children, according to the American Migraine Foundation. The headaches can strike children as early as age 3 or 4 years, said Robert Little, MD, a pediatric neurologist at Phoenix Children’s Hospital.
Before puberty, boys report more migraine attacks than girls, according to the American Academy of Pediatrics. But that reverses in adolescence: By age 17, as many as 8% of boys and 23% of girls have had migraine. To diagnose migraine, Juliana H. VanderPluym, MD, associate professor of neurology at Mayo Clinic in Phoenix, said she uses the criteria published in the latest edition of the International Classification of Headache Disorders (ICHD): A patient must have had at least five attacks in their life; and in children and adolescents, the attacks must last no less than 2 hours.
In addition, the headaches should exhibit at least two out of four features:
1. Occur more on one side of the head than the other (although Dr. VanderPluym said in children and adolescents headaches often are bilateral).
2. Be of moderate to severe intensity.
3. Have a pounding or throbbing quality.
4. Grow worse with activity or cause an avoidance of activity.
If the attacks meet those criteria, clinicians should check to see if they meet at least one out of the two following:
1. Are sensitive to light and sounds.
2. Are associated with nausea and/or vomiting.
A clinician should consider whether the headaches are not better accounted for by another diagnosis, according to the ICHD criteria. But, Dr. VanderPluym warned that does not necessarily mean running a slew of tests.
“In the absence of red flag features, it is more than likely going to be migraine headache,” she said. That’s especially true if a child has a family history of migraine, as the condition is often passed down from parent to child.
Ultimately, the diagnosis is fairly simple and can be made in a minute or less, said Jack Gladstein, MD, a pediatrician at the University of Maryland whose research focuses on the clinical care of children and adolescents with headache.
“Migraine is acute,” Dr. Gladstein said. “It’s really bad. And it’s recurrent.”
First line of treatment
Whatever a patient takes to treat a migraine, they should hit it early and hard, Dr. Gladstein said.
“The first thing you say, as a primary care physician, is treat your migraine at first twinge, whatever you use. Don’t wait, don’t wish it away,” he said. “The longer you wait, the less chance anything will work.”
The second piece of advice, Dr. Gladstein said, is that whatever drug a patient is taking, they should be on the highest feasible dose. “Work as fast as you can to treat them. You want the brain to reset as quickly as you can,” he said.
Patients should begin with over-the-counter pain relievers, Dr. Little said. If those prove insufficient, they can try a triptan. Rizatriptan is the only such agent that the Food and Drug Administration has approved for children aged 6-17 years. Other drugs in the class – sumatriptan/naproxen, almotriptan, and zolmitriptan – are approved for children 12 and older.
Another migraine therapy recently approved for children aged 12 and older is the use of neurostimulators. “It’s helpful to be aware of them,” Dr. VanderPluym said.
However, if neurostimulators and acute medications prove insufficient, clinicians should warn patients not to up their doses of triptans. Rebound headaches can occur if patients take triptans more than twice a week, or a maximum 10 days per month.
Another possibility is to add a preventive therapy. One mild, first option is nutraceuticals, like riboflavin (vitamin B2) or magnesium, said Anisa F. Kelley, MD, a neurologist and associate director of the headache program at the Ann and Robert H. Lurie Children’s Hospital of Chicago.
“We don’t have definitive evidence, but they’re probably doing more benefit than they are harm,” Dr. Kelley said of these therapies. “In patients who have anywhere from 4 to 8 migraine days a month, where you’re in that in-between period where you don’t necessarily need a [prescription] prophylactic, I will often start with a nutraceutical,” Dr. Kelley said.
For those patients who don’t respond to nutraceuticals, or who need more support, clinicians can prescribe amitriptyline or topiramate. Dr. VanderPluym said.
A 2017 study found such prophylactics to be no more effective than placebo in pediatric migraine patients, but experts caution the results should not be considered definitive.
For one thing, the study enrolled a highly selective group of participants, with milder forms of migraine who may have improved anyway, Dr. VanderPluym said. All participants also received lifestyle counseling.
Every time participants came in for a follow-up, they were asked questions such as how much water were they drinking and how much sleep were they getting, Dr. Kelley noted. The takeaway, she said: “Pediatric and adolescent migraine [management] is very, very much reliant on lifestyle factors.”
Lifestyle triggers
Clinicians should counsel their migraine patients about lifestyle changes, experts said. Getting adequate sleep, staying hydrated, and managing stress can help reduce the intensity and frequency of attacks.
Migraine patients should also be mindful of their screen time, Dr. Kelley added.
“I’ve had lots and lots of patients who find excessive screen time will trigger or worsen migraine,” she said.
As for other potential triggers of attacks, the evidence is mixed.
“There’s clearly an association with disrupted sleep and migraine, and that has been very well established,” Dr. Little said. “And there is some modest amount of evidence that regular exercise can be helpful.” But for reported food triggers, he said, there have been very inconclusive results.
Commonly reported triggers include MSG, red wine, chocolate, and aged cheese. When Dr. Little’s patients keep headache diaries, tracking their meals alongside when they got migraine attacks, they often discover individualized triggers – strawberries, for instance, in one case, he said.
Scientists believe migraines result from the inappropriate activation of the trigeminal ganglion. “The question is, what causes it to get triggered? And how does it get triggered?” Dr. Gladstein said. “And that’s where there’s a lot of difference of opinion and no conclusive evidence.” Clinicians also should make sure that something else – usually depression, anxiety, insomnia, and dizziness – is not hindering effective migraine management. “If someone has terrible insomnia, until you treat the insomnia, the headaches aren’t going to get better,” he said.
As for Mira, her migraine attacks did not significantly improve, despite trying triptans, prophylactics, lifestyle changes, and shots to block nerve pain. When the headaches threatened Mira’s chance to go to her prom, her neurologist suggested trying something different. The physician persuaded the family’s insurance to cover a calcitonin gene-related peptide antagonist, an injectable monoclonal antibody treatment for migraine that the FDA has currently approved only for use in adults.
The difference for Mira has been extraordinary.
“I can do so much more than I was able to do,” said Mira, who attended the dance migraine free. “I feel liberated.”
It’s only migraine
One of the greatest challenges in diagnosing migraine can be reassuring the patient, the parents, even clinicians themselves that migraine really is the cause of all this pain and discomfort, experts said.
“A lot of migraine treatment actually comes down to migraine education,” Dr. VanderPluym said.
Patients and their parents often wonder how they can be sure that this pain is not resulting from something more dangerous than migraine, Dr. Little said. In these cases, he cites practice guidelines published by the American Academy of Neurology.
“The gist of those guidelines is that most pediatric patients do not need further workup,” he said. “But I think that there’s always a fear that you’re missing something because we don’t have a test that we can do” for migraine.
Some warning signs that further tests might be warranted, Dr. Kelley said, include:
- Headaches that wake a patient up in the middle of the night.
- Headaches that start first thing in the morning, especially those that include vomiting.
- A headache pattern that suddenly gets much worse.
- Certain symptoms that accompany the headache, such as tingling, numbness or double vision.
Although all of these signs can still stem from migraines – tingling or numbness, for instance, can be signs of migraine aura – running additional tests can rule out more serious concerns, she said.
By the time Mira Halker started high school, hardly a day passed that she wasn’t either getting a migraine attack or recovering from one. She missed volleyball team practice. She missed classes. She missed social events. And few people understood. After all, she looked healthy.
“A lot of times, people think I’m faking it,” said Mira, now 16, who lives in Phoenix. Friends called her flaky; her volleyball coaches questioned her dedication to the team. “I’m like, ‘I’m not trying to get out of this. This is not what this is about,’ ” she said.
Her mother, Rashmi B. Halker Singh, MD, is a neurologist at Mayo Clinic who happens to specialize in migraine. Even so, finding a solution was not easy. Neither ibuprofen nor triptans, nor various preventive measures such as a daily prescription for topiramate controlled the pain and associated symptoms. Mira was barely making it through her school day and had to quit volleyball. Then, in the spring of 10th grade, Mira told her mother that she couldn’t go to prom because the loud noises and lights could give her a migraine attack.
Mother and daughter decided it was time to get even more aggressive. “There are these key moments in life that you can’t get back,” Dr. Singh said. “Migraine steals so much from you.”
Diagnosis
One of the challenges Mira’s physicians faced was deciding which medications and other therapies to prescribe to a teenager. Drug companies have been releasing a steady stream of new treatments for migraine headaches, and researchers promise more are on the way soon. Here’s what works for children, what hasn’t yet been approved for use with minors, and how to diagnose migraines in the first place, from experts at some of the nation’s leading pediatric headache centers.
Migraine affects about 10% of children, according to the American Migraine Foundation. The headaches can strike children as early as age 3 or 4 years, said Robert Little, MD, a pediatric neurologist at Phoenix Children’s Hospital.
Before puberty, boys report more migraine attacks than girls, according to the American Academy of Pediatrics. But that reverses in adolescence: By age 17, as many as 8% of boys and 23% of girls have had migraine. To diagnose migraine, Juliana H. VanderPluym, MD, associate professor of neurology at Mayo Clinic in Phoenix, said she uses the criteria published in the latest edition of the International Classification of Headache Disorders (ICHD): A patient must have had at least five attacks in their life; and in children and adolescents, the attacks must last no less than 2 hours.
In addition, the headaches should exhibit at least two out of four features:
1. Occur more on one side of the head than the other (although Dr. VanderPluym said in children and adolescents headaches often are bilateral).
2. Be of moderate to severe intensity.
3. Have a pounding or throbbing quality.
4. Grow worse with activity or cause an avoidance of activity.
If the attacks meet those criteria, clinicians should check to see if they meet at least one out of the two following:
1. Are sensitive to light and sounds.
2. Are associated with nausea and/or vomiting.
A clinician should consider whether the headaches are not better accounted for by another diagnosis, according to the ICHD criteria. But, Dr. VanderPluym warned that does not necessarily mean running a slew of tests.
“In the absence of red flag features, it is more than likely going to be migraine headache,” she said. That’s especially true if a child has a family history of migraine, as the condition is often passed down from parent to child.
Ultimately, the diagnosis is fairly simple and can be made in a minute or less, said Jack Gladstein, MD, a pediatrician at the University of Maryland whose research focuses on the clinical care of children and adolescents with headache.
“Migraine is acute,” Dr. Gladstein said. “It’s really bad. And it’s recurrent.”
First line of treatment
Whatever a patient takes to treat a migraine, they should hit it early and hard, Dr. Gladstein said.
“The first thing you say, as a primary care physician, is treat your migraine at first twinge, whatever you use. Don’t wait, don’t wish it away,” he said. “The longer you wait, the less chance anything will work.”
The second piece of advice, Dr. Gladstein said, is that whatever drug a patient is taking, they should be on the highest feasible dose. “Work as fast as you can to treat them. You want the brain to reset as quickly as you can,” he said.
Patients should begin with over-the-counter pain relievers, Dr. Little said. If those prove insufficient, they can try a triptan. Rizatriptan is the only such agent that the Food and Drug Administration has approved for children aged 6-17 years. Other drugs in the class – sumatriptan/naproxen, almotriptan, and zolmitriptan – are approved for children 12 and older.
Another migraine therapy recently approved for children aged 12 and older is the use of neurostimulators. “It’s helpful to be aware of them,” Dr. VanderPluym said.
However, if neurostimulators and acute medications prove insufficient, clinicians should warn patients not to up their doses of triptans. Rebound headaches can occur if patients take triptans more than twice a week, or a maximum 10 days per month.
Another possibility is to add a preventive therapy. One mild, first option is nutraceuticals, like riboflavin (vitamin B2) or magnesium, said Anisa F. Kelley, MD, a neurologist and associate director of the headache program at the Ann and Robert H. Lurie Children’s Hospital of Chicago.
“We don’t have definitive evidence, but they’re probably doing more benefit than they are harm,” Dr. Kelley said of these therapies. “In patients who have anywhere from 4 to 8 migraine days a month, where you’re in that in-between period where you don’t necessarily need a [prescription] prophylactic, I will often start with a nutraceutical,” Dr. Kelley said.
For those patients who don’t respond to nutraceuticals, or who need more support, clinicians can prescribe amitriptyline or topiramate. Dr. VanderPluym said.
A 2017 study found such prophylactics to be no more effective than placebo in pediatric migraine patients, but experts caution the results should not be considered definitive.
For one thing, the study enrolled a highly selective group of participants, with milder forms of migraine who may have improved anyway, Dr. VanderPluym said. All participants also received lifestyle counseling.
Every time participants came in for a follow-up, they were asked questions such as how much water were they drinking and how much sleep were they getting, Dr. Kelley noted. The takeaway, she said: “Pediatric and adolescent migraine [management] is very, very much reliant on lifestyle factors.”
Lifestyle triggers
Clinicians should counsel their migraine patients about lifestyle changes, experts said. Getting adequate sleep, staying hydrated, and managing stress can help reduce the intensity and frequency of attacks.
Migraine patients should also be mindful of their screen time, Dr. Kelley added.
“I’ve had lots and lots of patients who find excessive screen time will trigger or worsen migraine,” she said.
As for other potential triggers of attacks, the evidence is mixed.
“There’s clearly an association with disrupted sleep and migraine, and that has been very well established,” Dr. Little said. “And there is some modest amount of evidence that regular exercise can be helpful.” But for reported food triggers, he said, there have been very inconclusive results.
Commonly reported triggers include MSG, red wine, chocolate, and aged cheese. When Dr. Little’s patients keep headache diaries, tracking their meals alongside when they got migraine attacks, they often discover individualized triggers – strawberries, for instance, in one case, he said.
Scientists believe migraines result from the inappropriate activation of the trigeminal ganglion. “The question is, what causes it to get triggered? And how does it get triggered?” Dr. Gladstein said. “And that’s where there’s a lot of difference of opinion and no conclusive evidence.” Clinicians also should make sure that something else – usually depression, anxiety, insomnia, and dizziness – is not hindering effective migraine management. “If someone has terrible insomnia, until you treat the insomnia, the headaches aren’t going to get better,” he said.
As for Mira, her migraine attacks did not significantly improve, despite trying triptans, prophylactics, lifestyle changes, and shots to block nerve pain. When the headaches threatened Mira’s chance to go to her prom, her neurologist suggested trying something different. The physician persuaded the family’s insurance to cover a calcitonin gene-related peptide antagonist, an injectable monoclonal antibody treatment for migraine that the FDA has currently approved only for use in adults.
The difference for Mira has been extraordinary.
“I can do so much more than I was able to do,” said Mira, who attended the dance migraine free. “I feel liberated.”
It’s only migraine
One of the greatest challenges in diagnosing migraine can be reassuring the patient, the parents, even clinicians themselves that migraine really is the cause of all this pain and discomfort, experts said.
“A lot of migraine treatment actually comes down to migraine education,” Dr. VanderPluym said.
Patients and their parents often wonder how they can be sure that this pain is not resulting from something more dangerous than migraine, Dr. Little said. In these cases, he cites practice guidelines published by the American Academy of Neurology.
“The gist of those guidelines is that most pediatric patients do not need further workup,” he said. “But I think that there’s always a fear that you’re missing something because we don’t have a test that we can do” for migraine.
Some warning signs that further tests might be warranted, Dr. Kelley said, include:
- Headaches that wake a patient up in the middle of the night.
- Headaches that start first thing in the morning, especially those that include vomiting.
- A headache pattern that suddenly gets much worse.
- Certain symptoms that accompany the headache, such as tingling, numbness or double vision.
Although all of these signs can still stem from migraines – tingling or numbness, for instance, can be signs of migraine aura – running additional tests can rule out more serious concerns, she said.
By the time Mira Halker started high school, hardly a day passed that she wasn’t either getting a migraine attack or recovering from one. She missed volleyball team practice. She missed classes. She missed social events. And few people understood. After all, she looked healthy.
“A lot of times, people think I’m faking it,” said Mira, now 16, who lives in Phoenix. Friends called her flaky; her volleyball coaches questioned her dedication to the team. “I’m like, ‘I’m not trying to get out of this. This is not what this is about,’ ” she said.
Her mother, Rashmi B. Halker Singh, MD, is a neurologist at Mayo Clinic who happens to specialize in migraine. Even so, finding a solution was not easy. Neither ibuprofen nor triptans, nor various preventive measures such as a daily prescription for topiramate controlled the pain and associated symptoms. Mira was barely making it through her school day and had to quit volleyball. Then, in the spring of 10th grade, Mira told her mother that she couldn’t go to prom because the loud noises and lights could give her a migraine attack.
Mother and daughter decided it was time to get even more aggressive. “There are these key moments in life that you can’t get back,” Dr. Singh said. “Migraine steals so much from you.”
Diagnosis
One of the challenges Mira’s physicians faced was deciding which medications and other therapies to prescribe to a teenager. Drug companies have been releasing a steady stream of new treatments for migraine headaches, and researchers promise more are on the way soon. Here’s what works for children, what hasn’t yet been approved for use with minors, and how to diagnose migraines in the first place, from experts at some of the nation’s leading pediatric headache centers.
Migraine affects about 10% of children, according to the American Migraine Foundation. The headaches can strike children as early as age 3 or 4 years, said Robert Little, MD, a pediatric neurologist at Phoenix Children’s Hospital.
Before puberty, boys report more migraine attacks than girls, according to the American Academy of Pediatrics. But that reverses in adolescence: By age 17, as many as 8% of boys and 23% of girls have had migraine. To diagnose migraine, Juliana H. VanderPluym, MD, associate professor of neurology at Mayo Clinic in Phoenix, said she uses the criteria published in the latest edition of the International Classification of Headache Disorders (ICHD): A patient must have had at least five attacks in their life; and in children and adolescents, the attacks must last no less than 2 hours.
In addition, the headaches should exhibit at least two out of four features:
1. Occur more on one side of the head than the other (although Dr. VanderPluym said in children and adolescents headaches often are bilateral).
2. Be of moderate to severe intensity.
3. Have a pounding or throbbing quality.
4. Grow worse with activity or cause an avoidance of activity.
If the attacks meet those criteria, clinicians should check to see if they meet at least one out of the two following:
1. Are sensitive to light and sounds.
2. Are associated with nausea and/or vomiting.
A clinician should consider whether the headaches are not better accounted for by another diagnosis, according to the ICHD criteria. But, Dr. VanderPluym warned that does not necessarily mean running a slew of tests.
“In the absence of red flag features, it is more than likely going to be migraine headache,” she said. That’s especially true if a child has a family history of migraine, as the condition is often passed down from parent to child.
Ultimately, the diagnosis is fairly simple and can be made in a minute or less, said Jack Gladstein, MD, a pediatrician at the University of Maryland whose research focuses on the clinical care of children and adolescents with headache.
“Migraine is acute,” Dr. Gladstein said. “It’s really bad. And it’s recurrent.”
First line of treatment
Whatever a patient takes to treat a migraine, they should hit it early and hard, Dr. Gladstein said.
“The first thing you say, as a primary care physician, is treat your migraine at first twinge, whatever you use. Don’t wait, don’t wish it away,” he said. “The longer you wait, the less chance anything will work.”
The second piece of advice, Dr. Gladstein said, is that whatever drug a patient is taking, they should be on the highest feasible dose. “Work as fast as you can to treat them. You want the brain to reset as quickly as you can,” he said.
Patients should begin with over-the-counter pain relievers, Dr. Little said. If those prove insufficient, they can try a triptan. Rizatriptan is the only such agent that the Food and Drug Administration has approved for children aged 6-17 years. Other drugs in the class – sumatriptan/naproxen, almotriptan, and zolmitriptan – are approved for children 12 and older.
Another migraine therapy recently approved for children aged 12 and older is the use of neurostimulators. “It’s helpful to be aware of them,” Dr. VanderPluym said.
However, if neurostimulators and acute medications prove insufficient, clinicians should warn patients not to up their doses of triptans. Rebound headaches can occur if patients take triptans more than twice a week, or a maximum 10 days per month.
Another possibility is to add a preventive therapy. One mild, first option is nutraceuticals, like riboflavin (vitamin B2) or magnesium, said Anisa F. Kelley, MD, a neurologist and associate director of the headache program at the Ann and Robert H. Lurie Children’s Hospital of Chicago.
“We don’t have definitive evidence, but they’re probably doing more benefit than they are harm,” Dr. Kelley said of these therapies. “In patients who have anywhere from 4 to 8 migraine days a month, where you’re in that in-between period where you don’t necessarily need a [prescription] prophylactic, I will often start with a nutraceutical,” Dr. Kelley said.
For those patients who don’t respond to nutraceuticals, or who need more support, clinicians can prescribe amitriptyline or topiramate. Dr. VanderPluym said.
A 2017 study found such prophylactics to be no more effective than placebo in pediatric migraine patients, but experts caution the results should not be considered definitive.
For one thing, the study enrolled a highly selective group of participants, with milder forms of migraine who may have improved anyway, Dr. VanderPluym said. All participants also received lifestyle counseling.
Every time participants came in for a follow-up, they were asked questions such as how much water were they drinking and how much sleep were they getting, Dr. Kelley noted. The takeaway, she said: “Pediatric and adolescent migraine [management] is very, very much reliant on lifestyle factors.”
Lifestyle triggers
Clinicians should counsel their migraine patients about lifestyle changes, experts said. Getting adequate sleep, staying hydrated, and managing stress can help reduce the intensity and frequency of attacks.
Migraine patients should also be mindful of their screen time, Dr. Kelley added.
“I’ve had lots and lots of patients who find excessive screen time will trigger or worsen migraine,” she said.
As for other potential triggers of attacks, the evidence is mixed.
“There’s clearly an association with disrupted sleep and migraine, and that has been very well established,” Dr. Little said. “And there is some modest amount of evidence that regular exercise can be helpful.” But for reported food triggers, he said, there have been very inconclusive results.
Commonly reported triggers include MSG, red wine, chocolate, and aged cheese. When Dr. Little’s patients keep headache diaries, tracking their meals alongside when they got migraine attacks, they often discover individualized triggers – strawberries, for instance, in one case, he said.
Scientists believe migraines result from the inappropriate activation of the trigeminal ganglion. “The question is, what causes it to get triggered? And how does it get triggered?” Dr. Gladstein said. “And that’s where there’s a lot of difference of opinion and no conclusive evidence.” Clinicians also should make sure that something else – usually depression, anxiety, insomnia, and dizziness – is not hindering effective migraine management. “If someone has terrible insomnia, until you treat the insomnia, the headaches aren’t going to get better,” he said.
As for Mira, her migraine attacks did not significantly improve, despite trying triptans, prophylactics, lifestyle changes, and shots to block nerve pain. When the headaches threatened Mira’s chance to go to her prom, her neurologist suggested trying something different. The physician persuaded the family’s insurance to cover a calcitonin gene-related peptide antagonist, an injectable monoclonal antibody treatment for migraine that the FDA has currently approved only for use in adults.
The difference for Mira has been extraordinary.
“I can do so much more than I was able to do,” said Mira, who attended the dance migraine free. “I feel liberated.”
It’s only migraine
One of the greatest challenges in diagnosing migraine can be reassuring the patient, the parents, even clinicians themselves that migraine really is the cause of all this pain and discomfort, experts said.
“A lot of migraine treatment actually comes down to migraine education,” Dr. VanderPluym said.
Patients and their parents often wonder how they can be sure that this pain is not resulting from something more dangerous than migraine, Dr. Little said. In these cases, he cites practice guidelines published by the American Academy of Neurology.
“The gist of those guidelines is that most pediatric patients do not need further workup,” he said. “But I think that there’s always a fear that you’re missing something because we don’t have a test that we can do” for migraine.
Some warning signs that further tests might be warranted, Dr. Kelley said, include:
- Headaches that wake a patient up in the middle of the night.
- Headaches that start first thing in the morning, especially those that include vomiting.
- A headache pattern that suddenly gets much worse.
- Certain symptoms that accompany the headache, such as tingling, numbness or double vision.
Although all of these signs can still stem from migraines – tingling or numbness, for instance, can be signs of migraine aura – running additional tests can rule out more serious concerns, she said.