Treating adults who have chronic hepatitis C (CHC) with direct-acting antivirals (DAAs) was linked with a lower risk of death and poor liver outcomes, in a new study.

Eiichi Ogawa, MD, PhD, with the department of general internal medicine, Kyushu University Hospital in Fukuoka, Japan, led the retrospective study of 245,596 adults with CHC. In the new research, which was published in JAMA Internal Medicine, the authors analyzed data from the Optum Clinformatics Data Mart (CDM) database, 2010-2021.

It was important to do the study because of limited and conflicting information – mostly from case reports – on safety of the DAAs when they were approved for CHC in 2014, said coauthor Mindie H. Nguyen, MD, in an interview.
 

‘DAA treatment is safe’

“The main message is that DAA treatment is safe,” said Dr. Nguyen, of the division of gastroenterology and hepatology at Stanford (Calif.) University Medical Center in Palo Alto. In the early days of treatment, physicians were treating the sickest patients with the DAAs, which may have introduced patient selection bias and caused lasting misperceptions about poor safety, she noted.

“I really hope to dispel this myth,” she said, adding that this study also shows improved liver and nonliver outcomes.

Of the total cohort in this study, 40,654 patients had one or more prescriptions for a DAA (without interferon) and 204,942 patients had not been treated.
 

All-cause mortality reduced by 57%

DAA treatment, vs. no treatment, was linked with a large and significant reduction (57%) in all-cause mortality. That finding was particularly notable, because it was seen regardless of age, sex, race and ethnicity, comorbidities, alcohol use, and presence of hepatocellular carcinoma or cirrhosis.

The authors noted that patients without cirrhosis are a population previously considered to receive less benefit from an HCV cure than patients with cirrhosis.

DAAs were associated with lower risk of hepatocellular carcinoma and decompensation as well as risk of nonliver outcomes, including diabetes, cardiovascular disease (CVD), and chronic kidney disease (CKD).
 

Lower risk of poor nonliver outcomes

The researchers found that when they compared DAA-treated patients with untreated patients, the incidences per 1,000 person-years of having diabetes were 30.2 vs. 37.2 (P less than .001), and of having kidney disease was 31.1 vs. 34.1 (P less than .001), respectively.

“This retrospective cohort study provides valuable information to physicians,” Noel Deep, MD, chief medical officer at Aspirus Langlade Hospital in Antigo, Wis., said, in an interview.

The study’s size helps confirm DAAs’ safety and benefit, and previously unknown added benefits, in treating CHC, he continued.
 

Large study confirms, introduces DAA benefits

Dr. Deep, who was not part of the study, noted that DAAs now show much promise in efficacy and tolerability in most people with chronic hepatitis C, including those with concomitant conditions such as CKD.

“Previous studies did not have such large-scale nationwide data. [The findings of the new study] greatly enhance our knowledge of DAA treatment for chronic hepatitis C patients across the spectrum from noncirrhotic to compensated cirrhotic to decompensated cirrhotic,” Dr. Deep said. “The added benefit of improved outcomes for diabetes, CVD, CKD, and nonliver cancers truly surprised me.”

Dr. Deep pointed out some limitations of the study, including that, as the authors acknowledge, only privately insured patients were included so results may not be generalizable to the underinsured/uninsured “who might have other risk factors, poorer health, and fewer resources.”

He added: “The data also may not be reflective of the outcomes in Asians who were, in my opinion, also underrepresented in this study.”

The authors cited the insurance claims database they used as a strength of the study, due to it containing information on 61 million people from across all regions of the United States.

Dr. Ogawa reports grants from Gilead Sciences outside the submitted work. Coauthor Dr. Nguyen reports institutional grants and advisory board fees from Gilead Sciences outside the submitted work. Another coauthor reports speaking/consulting fees from Gilead and Merck Sharp & Dohme outside the submitted work. No other disclosures were reported.

The Stanford Center for Population Health Sciences (PHS) supported this study by providing access to the PHS Data Core.

Dr. Deep reports no relevant financial relationships. He serves on the editorial advisory board of Internal Medicine News.
 

Treating adults who have chronic hepatitis C (CHC) with direct-acting antivirals (DAAs) was linked with a lower risk of death and poor liver outcomes, in a new study.

Eiichi Ogawa, MD, PhD, with the department of general internal medicine, Kyushu University Hospital in Fukuoka, Japan, led the retrospective study of 245,596 adults with CHC. In the new research, which was published in JAMA Internal Medicine, the authors analyzed data from the Optum Clinformatics Data Mart (CDM) database, 2010-2021.

It was important to do the study because of limited and conflicting information – mostly from case reports – on safety of the DAAs when they were approved for CHC in 2014, said coauthor Mindie H. Nguyen, MD, in an interview.
 

‘DAA treatment is safe’

“The main message is that DAA treatment is safe,” said Dr. Nguyen, of the division of gastroenterology and hepatology at Stanford (Calif.) University Medical Center in Palo Alto. In the early days of treatment, physicians were treating the sickest patients with the DAAs, which may have introduced patient selection bias and caused lasting misperceptions about poor safety, she noted.

“I really hope to dispel this myth,” she said, adding that this study also shows improved liver and nonliver outcomes.

Of the total cohort in this study, 40,654 patients had one or more prescriptions for a DAA (without interferon) and 204,942 patients had not been treated.
 

All-cause mortality reduced by 57%

DAA treatment, vs. no treatment, was linked with a large and significant reduction (57%) in all-cause mortality. That finding was particularly notable, because it was seen regardless of age, sex, race and ethnicity, comorbidities, alcohol use, and presence of hepatocellular carcinoma or cirrhosis.

The authors noted that patients without cirrhosis are a population previously considered to receive less benefit from an HCV cure than patients with cirrhosis.

DAAs were associated with lower risk of hepatocellular carcinoma and decompensation as well as risk of nonliver outcomes, including diabetes, cardiovascular disease (CVD), and chronic kidney disease (CKD).
 

Lower risk of poor nonliver outcomes

The researchers found that when they compared DAA-treated patients with untreated patients, the incidences per 1,000 person-years of having diabetes were 30.2 vs. 37.2 (P less than .001), and of having kidney disease was 31.1 vs. 34.1 (P less than .001), respectively.

“This retrospective cohort study provides valuable information to physicians,” Noel Deep, MD, chief medical officer at Aspirus Langlade Hospital in Antigo, Wis., said, in an interview.

The study’s size helps confirm DAAs’ safety and benefit, and previously unknown added benefits, in treating CHC, he continued.
 

Large study confirms, introduces DAA benefits

Dr. Deep, who was not part of the study, noted that DAAs now show much promise in efficacy and tolerability in most people with chronic hepatitis C, including those with concomitant conditions such as CKD.

“Previous studies did not have such large-scale nationwide data. [The findings of the new study] greatly enhance our knowledge of DAA treatment for chronic hepatitis C patients across the spectrum from noncirrhotic to compensated cirrhotic to decompensated cirrhotic,” Dr. Deep said. “The added benefit of improved outcomes for diabetes, CVD, CKD, and nonliver cancers truly surprised me.”

Dr. Deep pointed out some limitations of the study, including that, as the authors acknowledge, only privately insured patients were included so results may not be generalizable to the underinsured/uninsured “who might have other risk factors, poorer health, and fewer resources.”

He added: “The data also may not be reflective of the outcomes in Asians who were, in my opinion, also underrepresented in this study.”

The authors cited the insurance claims database they used as a strength of the study, due to it containing information on 61 million people from across all regions of the United States.

Dr. Ogawa reports grants from Gilead Sciences outside the submitted work. Coauthor Dr. Nguyen reports institutional grants and advisory board fees from Gilead Sciences outside the submitted work. Another coauthor reports speaking/consulting fees from Gilead and Merck Sharp & Dohme outside the submitted work. No other disclosures were reported.

The Stanford Center for Population Health Sciences (PHS) supported this study by providing access to the PHS Data Core.

Dr. Deep reports no relevant financial relationships. He serves on the editorial advisory board of Internal Medicine News.
 

Treating adults who have chronic hepatitis C (CHC) with direct-acting antivirals (DAAs) was linked with a lower risk of death and poor liver outcomes, in a new study.

Eiichi Ogawa, MD, PhD, with the department of general internal medicine, Kyushu University Hospital in Fukuoka, Japan, led the retrospective study of 245,596 adults with CHC. In the new research, which was published in JAMA Internal Medicine, the authors analyzed data from the Optum Clinformatics Data Mart (CDM) database, 2010-2021.

It was important to do the study because of limited and conflicting information – mostly from case reports – on safety of the DAAs when they were approved for CHC in 2014, said coauthor Mindie H. Nguyen, MD, in an interview.
 

‘DAA treatment is safe’

“The main message is that DAA treatment is safe,” said Dr. Nguyen, of the division of gastroenterology and hepatology at Stanford (Calif.) University Medical Center in Palo Alto. In the early days of treatment, physicians were treating the sickest patients with the DAAs, which may have introduced patient selection bias and caused lasting misperceptions about poor safety, she noted.

“I really hope to dispel this myth,” she said, adding that this study also shows improved liver and nonliver outcomes.

Of the total cohort in this study, 40,654 patients had one or more prescriptions for a DAA (without interferon) and 204,942 patients had not been treated.
 

All-cause mortality reduced by 57%

DAA treatment, vs. no treatment, was linked with a large and significant reduction (57%) in all-cause mortality. That finding was particularly notable, because it was seen regardless of age, sex, race and ethnicity, comorbidities, alcohol use, and presence of hepatocellular carcinoma or cirrhosis.

The authors noted that patients without cirrhosis are a population previously considered to receive less benefit from an HCV cure than patients with cirrhosis.

DAAs were associated with lower risk of hepatocellular carcinoma and decompensation as well as risk of nonliver outcomes, including diabetes, cardiovascular disease (CVD), and chronic kidney disease (CKD).
 

Lower risk of poor nonliver outcomes

The researchers found that when they compared DAA-treated patients with untreated patients, the incidences per 1,000 person-years of having diabetes were 30.2 vs. 37.2 (P less than .001), and of having kidney disease was 31.1 vs. 34.1 (P less than .001), respectively.

“This retrospective cohort study provides valuable information to physicians,” Noel Deep, MD, chief medical officer at Aspirus Langlade Hospital in Antigo, Wis., said, in an interview.

The study’s size helps confirm DAAs’ safety and benefit, and previously unknown added benefits, in treating CHC, he continued.
 

Large study confirms, introduces DAA benefits

Dr. Deep, who was not part of the study, noted that DAAs now show much promise in efficacy and tolerability in most people with chronic hepatitis C, including those with concomitant conditions such as CKD.

“Previous studies did not have such large-scale nationwide data. [The findings of the new study] greatly enhance our knowledge of DAA treatment for chronic hepatitis C patients across the spectrum from noncirrhotic to compensated cirrhotic to decompensated cirrhotic,” Dr. Deep said. “The added benefit of improved outcomes for diabetes, CVD, CKD, and nonliver cancers truly surprised me.”

Dr. Deep pointed out some limitations of the study, including that, as the authors acknowledge, only privately insured patients were included so results may not be generalizable to the underinsured/uninsured “who might have other risk factors, poorer health, and fewer resources.”

He added: “The data also may not be reflective of the outcomes in Asians who were, in my opinion, also underrepresented in this study.”

The authors cited the insurance claims database they used as a strength of the study, due to it containing information on 61 million people from across all regions of the United States.

Dr. Ogawa reports grants from Gilead Sciences outside the submitted work. Coauthor Dr. Nguyen reports institutional grants and advisory board fees from Gilead Sciences outside the submitted work. Another coauthor reports speaking/consulting fees from Gilead and Merck Sharp & Dohme outside the submitted work. No other disclosures were reported.

The Stanford Center for Population Health Sciences (PHS) supported this study by providing access to the PHS Data Core.

Dr. Deep reports no relevant financial relationships. He serves on the editorial advisory board of Internal Medicine News.
 

Interventional cardiologist Richard B. Zelman, MD, has filed a lawsuit against Cape Cod Hospital, Cape Cod Healthcare Inc., and its chief executive officer Michael K. Lauf, alleging that he was fired and maligned after raising concerns about poorly performed surgeries and poor ethical practices at the hospital.

Dr. Zelman, from Barnstable, Mass., has been affiliated with Cape Cod Hospital in Hyannis, Mass., for more than 30 years. He helped found the hospital’s Heart and Vascular Institute and has served as its medical director since 2018.

In his lawsuit filed Dec. 6, Dr. Zelman alleges that the defendants, under Mr. Lauf’s leadership, “placed profit above all else, including by prioritizing revenue generation over patient safety and public health.”

Dr. Zelman says the defendants supported him “to the extent his actions were profitable.”

Yet, when he raised patient safety concerns that harmed that bottom line, Dr. Zelman says the defendants retaliated against him, including by threatening his career and reputation and unlawfully terminating his employment with the hospital.

The complaint notes Dr. Zelman is bringing this action “to recover damages for violations of the Massachusetts Healthcare Provider Whistleblower Statute ... as well as for breach of contract and common law claims.”

Dr. Zelman’s complaint alleges the defendants refused to adequately address the “dangerous care and violations of the professional standards of practice” that he reported, “resulting in harmful and tragic consequences.”

It also alleges Mr. Lauf restricted the use of a cerebral protection device used in patients undergoing transcatheter aortic-valve replacement (TAVR) deemed to be at high risk for periprocedural stroke to only those patients whose insurance reimbursed at higher rates.

Dr. Zelman says he objected to this prohibition “in accordance with his contractual and ethical obligations to ensure treatment of patients without regard to their ability to pay.”

Dr. Zelman’s lawsuit further alleges that Mr. Lauf launched a “trumped-up” and “baseless, biased, and retaliatory sham” investigation against him.

In a statement sent to the Boston Globe, Cape Cod Hospital denied Dr. Zelman’s claims that the cardiologist was retaliated against for raising patient safety issues, or that the hospital didn’t take action to improve cardiac care at the facility.
 

Voiced concerns

In a statement sent to this news organization, Dr. Zelman, now in private practice, said, “Over the past 25 years, I have been instrumental in bringing advanced cardiac care to Cape Cod. My commitment has always been to delivering the same quality outcomes and safety as the academic centers in Boston.

“Unfortunately, over the past 5 years, there has been inadequate oversight by the hospital administration and problems have occurred that in my opinion have led to serious patient consequences,” Dr. Zelman stated.

He said he has “voiced concerns over several years and they have been ignored.”

He added that Cape Cod Hospital offered him a million-dollar contract as long as he agreed to immediately issue a written statement endorsing the quality and safety of the cardiac surgical program that no longer exists.

“No amount of money was going to buy my silence,” Dr. Zelman told this news organization.

In his lawsuit, Dr. Zelman is seeking an undisclosed amount in damages, including back and front pay, lost benefits, physical and emotional distress, and attorneys’ fees.

This news organization reached out to Cape Cod Hospital for comment but has not yet received a response.

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

Interventional cardiologist Richard B. Zelman, MD, has filed a lawsuit against Cape Cod Hospital, Cape Cod Healthcare Inc., and its chief executive officer Michael K. Lauf, alleging that he was fired and maligned after raising concerns about poorly performed surgeries and poor ethical practices at the hospital.

Dr. Zelman, from Barnstable, Mass., has been affiliated with Cape Cod Hospital in Hyannis, Mass., for more than 30 years. He helped found the hospital’s Heart and Vascular Institute and has served as its medical director since 2018.

In his lawsuit filed Dec. 6, Dr. Zelman alleges that the defendants, under Mr. Lauf’s leadership, “placed profit above all else, including by prioritizing revenue generation over patient safety and public health.”

Dr. Zelman says the defendants supported him “to the extent his actions were profitable.”

Yet, when he raised patient safety concerns that harmed that bottom line, Dr. Zelman says the defendants retaliated against him, including by threatening his career and reputation and unlawfully terminating his employment with the hospital.

The complaint notes Dr. Zelman is bringing this action “to recover damages for violations of the Massachusetts Healthcare Provider Whistleblower Statute ... as well as for breach of contract and common law claims.”

Dr. Zelman’s complaint alleges the defendants refused to adequately address the “dangerous care and violations of the professional standards of practice” that he reported, “resulting in harmful and tragic consequences.”

It also alleges Mr. Lauf restricted the use of a cerebral protection device used in patients undergoing transcatheter aortic-valve replacement (TAVR) deemed to be at high risk for periprocedural stroke to only those patients whose insurance reimbursed at higher rates.

Dr. Zelman says he objected to this prohibition “in accordance with his contractual and ethical obligations to ensure treatment of patients without regard to their ability to pay.”

Dr. Zelman’s lawsuit further alleges that Mr. Lauf launched a “trumped-up” and “baseless, biased, and retaliatory sham” investigation against him.

In a statement sent to the Boston Globe, Cape Cod Hospital denied Dr. Zelman’s claims that the cardiologist was retaliated against for raising patient safety issues, or that the hospital didn’t take action to improve cardiac care at the facility.
 

Voiced concerns

In a statement sent to this news organization, Dr. Zelman, now in private practice, said, “Over the past 25 years, I have been instrumental in bringing advanced cardiac care to Cape Cod. My commitment has always been to delivering the same quality outcomes and safety as the academic centers in Boston.

“Unfortunately, over the past 5 years, there has been inadequate oversight by the hospital administration and problems have occurred that in my opinion have led to serious patient consequences,” Dr. Zelman stated.

He said he has “voiced concerns over several years and they have been ignored.”

He added that Cape Cod Hospital offered him a million-dollar contract as long as he agreed to immediately issue a written statement endorsing the quality and safety of the cardiac surgical program that no longer exists.

“No amount of money was going to buy my silence,” Dr. Zelman told this news organization.

In his lawsuit, Dr. Zelman is seeking an undisclosed amount in damages, including back and front pay, lost benefits, physical and emotional distress, and attorneys’ fees.

This news organization reached out to Cape Cod Hospital for comment but has not yet received a response.

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

Interventional cardiologist Richard B. Zelman, MD, has filed a lawsuit against Cape Cod Hospital, Cape Cod Healthcare Inc., and its chief executive officer Michael K. Lauf, alleging that he was fired and maligned after raising concerns about poorly performed surgeries and poor ethical practices at the hospital.

Dr. Zelman, from Barnstable, Mass., has been affiliated with Cape Cod Hospital in Hyannis, Mass., for more than 30 years. He helped found the hospital’s Heart and Vascular Institute and has served as its medical director since 2018.

In his lawsuit filed Dec. 6, Dr. Zelman alleges that the defendants, under Mr. Lauf’s leadership, “placed profit above all else, including by prioritizing revenue generation over patient safety and public health.”

Dr. Zelman says the defendants supported him “to the extent his actions were profitable.”

Yet, when he raised patient safety concerns that harmed that bottom line, Dr. Zelman says the defendants retaliated against him, including by threatening his career and reputation and unlawfully terminating his employment with the hospital.

The complaint notes Dr. Zelman is bringing this action “to recover damages for violations of the Massachusetts Healthcare Provider Whistleblower Statute ... as well as for breach of contract and common law claims.”

Dr. Zelman’s complaint alleges the defendants refused to adequately address the “dangerous care and violations of the professional standards of practice” that he reported, “resulting in harmful and tragic consequences.”

It also alleges Mr. Lauf restricted the use of a cerebral protection device used in patients undergoing transcatheter aortic-valve replacement (TAVR) deemed to be at high risk for periprocedural stroke to only those patients whose insurance reimbursed at higher rates.

Dr. Zelman says he objected to this prohibition “in accordance with his contractual and ethical obligations to ensure treatment of patients without regard to their ability to pay.”

Dr. Zelman’s lawsuit further alleges that Mr. Lauf launched a “trumped-up” and “baseless, biased, and retaliatory sham” investigation against him.

In a statement sent to the Boston Globe, Cape Cod Hospital denied Dr. Zelman’s claims that the cardiologist was retaliated against for raising patient safety issues, or that the hospital didn’t take action to improve cardiac care at the facility.
 

Voiced concerns

In a statement sent to this news organization, Dr. Zelman, now in private practice, said, “Over the past 25 years, I have been instrumental in bringing advanced cardiac care to Cape Cod. My commitment has always been to delivering the same quality outcomes and safety as the academic centers in Boston.

“Unfortunately, over the past 5 years, there has been inadequate oversight by the hospital administration and problems have occurred that in my opinion have led to serious patient consequences,” Dr. Zelman stated.

He said he has “voiced concerns over several years and they have been ignored.”

He added that Cape Cod Hospital offered him a million-dollar contract as long as he agreed to immediately issue a written statement endorsing the quality and safety of the cardiac surgical program that no longer exists.

“No amount of money was going to buy my silence,” Dr. Zelman told this news organization.

In his lawsuit, Dr. Zelman is seeking an undisclosed amount in damages, including back and front pay, lost benefits, physical and emotional distress, and attorneys’ fees.

This news organization reached out to Cape Cod Hospital for comment but has not yet received a response.

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

NASHVILLE, TENN. – A study of more than 4 million births over 20 years in five Scandinavian countries has reported that three antiseizure medications should be used with caution in women of child-bearing age because they were associated with low birth weights.

In results presented at the annual meeting of the American Epilepsy Society, Jakob Christensen, MD, DSc, PhD, a professor at Aarhus University Hospital in Denmark, said that the study found that carbamazepine, oxcarbazepine, and topiramate were associated with low birth weight and increased risk of infants being born small for gestational age.

• Carbamazepine, 1.44 (95% confidence interval [CI], 1.21-1.71).
• Oxcarbazepine, 1.32 (95% CI, 1.03-1.69).
• Topiramate, 1.60 (95% CI, 1.15-2.24).
• Pregabalin, 1.23 (95% CI, 1.02-1.48).
• Clobazam, 4.36 (95% CI, 1.66-11.45).

The odds ratios for being born small for gestational age were:

• Carbamazepine, 1.25 (95% CI, 1.11-1.41).
• Oxcarbazepine, 1.48 (95% CI, 1.27-1.73).
• Topiramate, 1.52 (95% CI, 1.20-1.91).

“Prenatal exposure to carbamazepine, oxcarbazepine, and topiramate were associated with all estimates of adverse birth weight outcomes, thus confirming results from preclinical studies in animals and previous smaller studies in humans,” Dr. Christensen said.

He noted a lack of evidence for newer medications because their use was relatively low over the 20 years of the study. “However, for drugs like lamotrigine where we have a high number of exposed children, the finding of no association with low birth weight is reassuring, indicating the drug is safe,” Dr. Christensen said.
 

Use with caution

This study adds supportive evidence for expanding the list of antiseizure medications associated with small for gestational age infants, Elizabeth Gerard, MD, director of the Women with Epilepsy Program and associate professor of neurology at Northwestern University in Chicago, said in an interview.

“Previous clinical trials demonstrated that topiramate and zonisamide as well as phenobarbital were associated with small for gestational age,” she said. “This study added to the list carbamazepine and oxcarbazepine. Previously it wasn’t clear from clinical data but there were some hints that carbamazepine and oxcarbazepine might be associated with small for gestational age, but this is the first study to present robust data that carbamazepine and oxcarbazepine are associated with small for gestational age infants as well.”

She noted that these drugs can be used cautiously in women of child-bearing age and pregnant women. “I think these lines of evidence suggest that women with epilepsy should be more carefully monitored, at least with these high-quality, standard-of-care drugs, for fetal growth monitoring and perhaps most of them, especially those on at-risk drugs, should have detailed growth gradings,” Dr. Gerard said. Pregnant women on these antiseizure medications should have ultrasound beginning at 24 weeks gestation to monitor fetal growth, she said.

The NordForsk Nordic Program and Health and Welfare and the Independent Research Fund Denmark provided funding for the study. Dr. Christensen disclosed financial relationships with Union Chimique Belge Nordic and Eisai. Dr. Gerard disclosed relationships with Xenon Pharmaceuticals and Eisai.

NASHVILLE, TENN. – A study of more than 4 million births over 20 years in five Scandinavian countries has reported that three antiseizure medications should be used with caution in women of child-bearing age because they were associated with low birth weights.

In results presented at the annual meeting of the American Epilepsy Society, Jakob Christensen, MD, DSc, PhD, a professor at Aarhus University Hospital in Denmark, said that the study found that carbamazepine, oxcarbazepine, and topiramate were associated with low birth weight and increased risk of infants being born small for gestational age.

• Carbamazepine, 1.44 (95% confidence interval [CI], 1.21-1.71).
• Oxcarbazepine, 1.32 (95% CI, 1.03-1.69).
• Topiramate, 1.60 (95% CI, 1.15-2.24).
• Pregabalin, 1.23 (95% CI, 1.02-1.48).
• Clobazam, 4.36 (95% CI, 1.66-11.45).

The odds ratios for being born small for gestational age were:

• Carbamazepine, 1.25 (95% CI, 1.11-1.41).
• Oxcarbazepine, 1.48 (95% CI, 1.27-1.73).
• Topiramate, 1.52 (95% CI, 1.20-1.91).

“Prenatal exposure to carbamazepine, oxcarbazepine, and topiramate were associated with all estimates of adverse birth weight outcomes, thus confirming results from preclinical studies in animals and previous smaller studies in humans,” Dr. Christensen said.

He noted a lack of evidence for newer medications because their use was relatively low over the 20 years of the study. “However, for drugs like lamotrigine where we have a high number of exposed children, the finding of no association with low birth weight is reassuring, indicating the drug is safe,” Dr. Christensen said.
 

Use with caution

This study adds supportive evidence for expanding the list of antiseizure medications associated with small for gestational age infants, Elizabeth Gerard, MD, director of the Women with Epilepsy Program and associate professor of neurology at Northwestern University in Chicago, said in an interview.

“Previous clinical trials demonstrated that topiramate and zonisamide as well as phenobarbital were associated with small for gestational age,” she said. “This study added to the list carbamazepine and oxcarbazepine. Previously it wasn’t clear from clinical data but there were some hints that carbamazepine and oxcarbazepine might be associated with small for gestational age, but this is the first study to present robust data that carbamazepine and oxcarbazepine are associated with small for gestational age infants as well.”

She noted that these drugs can be used cautiously in women of child-bearing age and pregnant women. “I think these lines of evidence suggest that women with epilepsy should be more carefully monitored, at least with these high-quality, standard-of-care drugs, for fetal growth monitoring and perhaps most of them, especially those on at-risk drugs, should have detailed growth gradings,” Dr. Gerard said. Pregnant women on these antiseizure medications should have ultrasound beginning at 24 weeks gestation to monitor fetal growth, she said.

The NordForsk Nordic Program and Health and Welfare and the Independent Research Fund Denmark provided funding for the study. Dr. Christensen disclosed financial relationships with Union Chimique Belge Nordic and Eisai. Dr. Gerard disclosed relationships with Xenon Pharmaceuticals and Eisai.

NASHVILLE, TENN. – A study of more than 4 million births over 20 years in five Scandinavian countries has reported that three antiseizure medications should be used with caution in women of child-bearing age because they were associated with low birth weights.

In results presented at the annual meeting of the American Epilepsy Society, Jakob Christensen, MD, DSc, PhD, a professor at Aarhus University Hospital in Denmark, said that the study found that carbamazepine, oxcarbazepine, and topiramate were associated with low birth weight and increased risk of infants being born small for gestational age.

• Carbamazepine, 1.44 (95% confidence interval [CI], 1.21-1.71).
• Oxcarbazepine, 1.32 (95% CI, 1.03-1.69).
• Topiramate, 1.60 (95% CI, 1.15-2.24).
• Pregabalin, 1.23 (95% CI, 1.02-1.48).
• Clobazam, 4.36 (95% CI, 1.66-11.45).

The odds ratios for being born small for gestational age were:

• Carbamazepine, 1.25 (95% CI, 1.11-1.41).
• Oxcarbazepine, 1.48 (95% CI, 1.27-1.73).
• Topiramate, 1.52 (95% CI, 1.20-1.91).

“Prenatal exposure to carbamazepine, oxcarbazepine, and topiramate were associated with all estimates of adverse birth weight outcomes, thus confirming results from preclinical studies in animals and previous smaller studies in humans,” Dr. Christensen said.

He noted a lack of evidence for newer medications because their use was relatively low over the 20 years of the study. “However, for drugs like lamotrigine where we have a high number of exposed children, the finding of no association with low birth weight is reassuring, indicating the drug is safe,” Dr. Christensen said.
 

Use with caution

This study adds supportive evidence for expanding the list of antiseizure medications associated with small for gestational age infants, Elizabeth Gerard, MD, director of the Women with Epilepsy Program and associate professor of neurology at Northwestern University in Chicago, said in an interview.

“Previous clinical trials demonstrated that topiramate and zonisamide as well as phenobarbital were associated with small for gestational age,” she said. “This study added to the list carbamazepine and oxcarbazepine. Previously it wasn’t clear from clinical data but there were some hints that carbamazepine and oxcarbazepine might be associated with small for gestational age, but this is the first study to present robust data that carbamazepine and oxcarbazepine are associated with small for gestational age infants as well.”

She noted that these drugs can be used cautiously in women of child-bearing age and pregnant women. “I think these lines of evidence suggest that women with epilepsy should be more carefully monitored, at least with these high-quality, standard-of-care drugs, for fetal growth monitoring and perhaps most of them, especially those on at-risk drugs, should have detailed growth gradings,” Dr. Gerard said. Pregnant women on these antiseizure medications should have ultrasound beginning at 24 weeks gestation to monitor fetal growth, she said.

The NordForsk Nordic Program and Health and Welfare and the Independent Research Fund Denmark provided funding for the study. Dr. Christensen disclosed financial relationships with Union Chimique Belge Nordic and Eisai. Dr. Gerard disclosed relationships with Xenon Pharmaceuticals and Eisai.

Since its inception in 1996, the CHEST Foundation has served patients and clinicians alike by supporting initiatives to educate, empower, and improve, but this may have been one of its most exciting and impactful years yet. As 2022 draws to a close, look back at the progress made over the past 12 months and the initiatives that will help the Foundation continue to support clinicians and patients in 2023.

Collaboration and communication key in 2022

2022 saw the launch of two new initiatives that will be integral to improving patient care in the years to come: The First 5 Minutes^™ and Bridging Specialties^™: Timely Diagnosis for ILD Patients.

A collaborative partnership between CHEST and Three Lakes Foundation, Bridging Specialties brings together pulmonologists and primary care physicians to define a clearer clinician-guided approach to diagnosis for ILDs like pulmonary fibrosis (PF).

A Steering Committee of multidisciplinary clinicians – including pulmonologists, primary care physicians, and a nurse practitioner – have led the development of important resources including a white paper highlighting the most recent data into delays in diagnosis.

Plus, a newly launched ILD Clinician Toolkit offers the following and more:

• An early detection learning module offering information about reasons for delayed ILD diagnosis, symptoms to watch and listen for (like crackles on auscultation), suggested patient workups, and recommendations on proactive steps to take, including when to refer to a pulmonologist;
• A decision-making tool offering interactive simulated patient visits; and
• Radiologic imaging videos covering key patterns, common CT scan appearances and imaging features that can help in diagnosis of ILDs.

Clinicians can access the toolkit at bit.ly/Bridging-Specialties.
 

The First 5 Minutes

The First 5 Minutes initiative, developed in response to themes identified during the Foundation’s Listening Tour in 2020, kicked off in Bexar County, TX, in June with an in-person pilot training program at the University of Texas Health Science Center.

There, relationship-centered communication trainers from the Academy of Communication Healthcare led 18 clinicians through interactive activities on empathetic listening and trust-building communication skills.

Attendees at CHEST 2022 had the opportunity to participate in a similar interactive session on Monday, October 17, where they practiced empathetic listening skills with fellow attendees and learned how establishing trust with patients in the first 5 minutes of interactions can lead to more efficient communication and improve patient adherence. Learn more at bit.ly/First-5-Minutes.

CHEST gratefully acknowledges the following founding supporters of the First 5 Minutes^™: Amgen, AstraZeneca, Bexar County, Novartis, Regeneron, Sanofi, and VIATRIS.
 

Making medicine a more inclusive practice

In February 2022, the American College of Chest Physicians (CHEST), the American Thoracic Society (ATS), and the American Lung Association announced a partnership with the prestigious Harold Amos Medical Faculty Development Program (AMFDP), a Robert Wood Johnson Foundation initiative, to sponsor a scholar in pulmonary and critical care medicine.

The recipient of that grant, George Alba, MD, Instructor of Medicine at Harvard Medical School and Pulmonary and Critical Care Physician at Massachusetts General, was announced earlier this year. Through his AMFDP award project, “Pulmonary Endothelial NEDD9 and Acute Lung Injury,” Dr. Alba seeks to advance NEDD9 antagonism as a potential therapeutic target in acute respiratory distress syndrome (ARDS).

“Growing up, I saw through my father’s example how education unlocks opportunities. Our community came together to help him on this path. Now a retired doctor of osteopathy in neonatology, it inspired me to pursue a career in medicine,” said Dr. Alba. “This award comes at a critical time in my junior faculty career: it allows me to continue pursuing my research in a meaningful way while also gaining new skills that will be critical for my ongoing career development.”

Visit bit.ly/3X4VphB to learn more about the AMFDP initiative and Dr. Alba.
 

Fun and fellowship – for a good cause

In addition, to all of this, the CHEST Foundation continued to host engaging events throughout the year to encourage connection, raise awareness, and fundraise for important initiatives.

This included the annual Belmont Stakes Dinner and Auction on June 11 in New York City. The fun-filled evening included a viewing of the 154th running of “The Championship Track,” a cocktail reception and plated dinner, a silent auction, a rooftop party, and insights from two patient advocates who turned their own experiences of living with chronic lung disease into incredible action on behalf of patients.

Three virtual wine nights in April, August, and December also invited numerous guests to learn more about imbibes from France, Italy, and California. Led by CHEST’s own resident wine aficionado, CEO Bob Musacchio, PhD, these events benefited the AMFDP, as well as other initiatives to improve patient care.

Another event that brought support to battling lung disease was the 9th Annual Irv Feldman Texas Hold 'Em Poker Tournament and Casino night jointly hosted by the Feldman Family Foundation and the CHEST Foundation. For the first time since early 2020, the event was held in-person after years of virtual tournaments. Funds raised from the event support education and resources to provide for a better quality of life for patients battling pulmonary fibrosis, a fibrotic lung disease with no cure.

2022 is special in another way. This year, the CHEST Foundation is offering an unmatched opportunity to one donor to attend CHEST 2023 in Honolulu, Hawai‘i for free. For every $250 you donate to the CHEST Foundation by December 31, 2022, you will receive an entry into a drawing for free registration, airfare (US only), and hotel accommodations.

Learn more about how you can donate to support initiatives like these – and make your mark on the practice of pulmonary, critical care, and sleep medicine – at foundation.chestnet.org.
 

Twenty-five years of life-changing grants

In addition to all of this, the CHEST Foundation provides financial grants to advance medicine and support to those in need. More than 12 million dollars later, the CHEST Foundation is proud to bolster the field of medicine and enhance patient care through this support. Learn more about the impact of grants from recent recipients in the September issue of CHEST Physician.

Since its inception in 1996, the CHEST Foundation has served patients and clinicians alike by supporting initiatives to educate, empower, and improve, but this may have been one of its most exciting and impactful years yet. As 2022 draws to a close, look back at the progress made over the past 12 months and the initiatives that will help the Foundation continue to support clinicians and patients in 2023.

Collaboration and communication key in 2022

2022 saw the launch of two new initiatives that will be integral to improving patient care in the years to come: The First 5 Minutes^™ and Bridging Specialties^™: Timely Diagnosis for ILD Patients.

A collaborative partnership between CHEST and Three Lakes Foundation, Bridging Specialties brings together pulmonologists and primary care physicians to define a clearer clinician-guided approach to diagnosis for ILDs like pulmonary fibrosis (PF).

A Steering Committee of multidisciplinary clinicians – including pulmonologists, primary care physicians, and a nurse practitioner – have led the development of important resources including a white paper highlighting the most recent data into delays in diagnosis.

Plus, a newly launched ILD Clinician Toolkit offers the following and more:

• An early detection learning module offering information about reasons for delayed ILD diagnosis, symptoms to watch and listen for (like crackles on auscultation), suggested patient workups, and recommendations on proactive steps to take, including when to refer to a pulmonologist;
• A decision-making tool offering interactive simulated patient visits; and
• Radiologic imaging videos covering key patterns, common CT scan appearances and imaging features that can help in diagnosis of ILDs.

Clinicians can access the toolkit at bit.ly/Bridging-Specialties.
 

The First 5 Minutes

The First 5 Minutes initiative, developed in response to themes identified during the Foundation’s Listening Tour in 2020, kicked off in Bexar County, TX, in June with an in-person pilot training program at the University of Texas Health Science Center.

There, relationship-centered communication trainers from the Academy of Communication Healthcare led 18 clinicians through interactive activities on empathetic listening and trust-building communication skills.

Attendees at CHEST 2022 had the opportunity to participate in a similar interactive session on Monday, October 17, where they practiced empathetic listening skills with fellow attendees and learned how establishing trust with patients in the first 5 minutes of interactions can lead to more efficient communication and improve patient adherence. Learn more at bit.ly/First-5-Minutes.

CHEST gratefully acknowledges the following founding supporters of the First 5 Minutes^™: Amgen, AstraZeneca, Bexar County, Novartis, Regeneron, Sanofi, and VIATRIS.
 

Making medicine a more inclusive practice

In February 2022, the American College of Chest Physicians (CHEST), the American Thoracic Society (ATS), and the American Lung Association announced a partnership with the prestigious Harold Amos Medical Faculty Development Program (AMFDP), a Robert Wood Johnson Foundation initiative, to sponsor a scholar in pulmonary and critical care medicine.

The recipient of that grant, George Alba, MD, Instructor of Medicine at Harvard Medical School and Pulmonary and Critical Care Physician at Massachusetts General, was announced earlier this year. Through his AMFDP award project, “Pulmonary Endothelial NEDD9 and Acute Lung Injury,” Dr. Alba seeks to advance NEDD9 antagonism as a potential therapeutic target in acute respiratory distress syndrome (ARDS).

“Growing up, I saw through my father’s example how education unlocks opportunities. Our community came together to help him on this path. Now a retired doctor of osteopathy in neonatology, it inspired me to pursue a career in medicine,” said Dr. Alba. “This award comes at a critical time in my junior faculty career: it allows me to continue pursuing my research in a meaningful way while also gaining new skills that will be critical for my ongoing career development.”

Visit bit.ly/3X4VphB to learn more about the AMFDP initiative and Dr. Alba.
 

Fun and fellowship – for a good cause

In addition, to all of this, the CHEST Foundation continued to host engaging events throughout the year to encourage connection, raise awareness, and fundraise for important initiatives.

This included the annual Belmont Stakes Dinner and Auction on June 11 in New York City. The fun-filled evening included a viewing of the 154th running of “The Championship Track,” a cocktail reception and plated dinner, a silent auction, a rooftop party, and insights from two patient advocates who turned their own experiences of living with chronic lung disease into incredible action on behalf of patients.

Three virtual wine nights in April, August, and December also invited numerous guests to learn more about imbibes from France, Italy, and California. Led by CHEST’s own resident wine aficionado, CEO Bob Musacchio, PhD, these events benefited the AMFDP, as well as other initiatives to improve patient care.

Another event that brought support to battling lung disease was the 9th Annual Irv Feldman Texas Hold 'Em Poker Tournament and Casino night jointly hosted by the Feldman Family Foundation and the CHEST Foundation. For the first time since early 2020, the event was held in-person after years of virtual tournaments. Funds raised from the event support education and resources to provide for a better quality of life for patients battling pulmonary fibrosis, a fibrotic lung disease with no cure.

2022 is special in another way. This year, the CHEST Foundation is offering an unmatched opportunity to one donor to attend CHEST 2023 in Honolulu, Hawai‘i for free. For every $250 you donate to the CHEST Foundation by December 31, 2022, you will receive an entry into a drawing for free registration, airfare (US only), and hotel accommodations.

Learn more about how you can donate to support initiatives like these – and make your mark on the practice of pulmonary, critical care, and sleep medicine – at foundation.chestnet.org.
 

Twenty-five years of life-changing grants

In addition to all of this, the CHEST Foundation provides financial grants to advance medicine and support to those in need. More than 12 million dollars later, the CHEST Foundation is proud to bolster the field of medicine and enhance patient care through this support. Learn more about the impact of grants from recent recipients in the September issue of CHEST Physician.

Since its inception in 1996, the CHEST Foundation has served patients and clinicians alike by supporting initiatives to educate, empower, and improve, but this may have been one of its most exciting and impactful years yet. As 2022 draws to a close, look back at the progress made over the past 12 months and the initiatives that will help the Foundation continue to support clinicians and patients in 2023.

Collaboration and communication key in 2022

2022 saw the launch of two new initiatives that will be integral to improving patient care in the years to come: The First 5 Minutes^™ and Bridging Specialties^™: Timely Diagnosis for ILD Patients.

A collaborative partnership between CHEST and Three Lakes Foundation, Bridging Specialties brings together pulmonologists and primary care physicians to define a clearer clinician-guided approach to diagnosis for ILDs like pulmonary fibrosis (PF).

A Steering Committee of multidisciplinary clinicians – including pulmonologists, primary care physicians, and a nurse practitioner – have led the development of important resources including a white paper highlighting the most recent data into delays in diagnosis.

Plus, a newly launched ILD Clinician Toolkit offers the following and more:

• An early detection learning module offering information about reasons for delayed ILD diagnosis, symptoms to watch and listen for (like crackles on auscultation), suggested patient workups, and recommendations on proactive steps to take, including when to refer to a pulmonologist;
• A decision-making tool offering interactive simulated patient visits; and
• Radiologic imaging videos covering key patterns, common CT scan appearances and imaging features that can help in diagnosis of ILDs.

Clinicians can access the toolkit at bit.ly/Bridging-Specialties.
 

The First 5 Minutes

The First 5 Minutes initiative, developed in response to themes identified during the Foundation’s Listening Tour in 2020, kicked off in Bexar County, TX, in June with an in-person pilot training program at the University of Texas Health Science Center.

There, relationship-centered communication trainers from the Academy of Communication Healthcare led 18 clinicians through interactive activities on empathetic listening and trust-building communication skills.

Attendees at CHEST 2022 had the opportunity to participate in a similar interactive session on Monday, October 17, where they practiced empathetic listening skills with fellow attendees and learned how establishing trust with patients in the first 5 minutes of interactions can lead to more efficient communication and improve patient adherence. Learn more at bit.ly/First-5-Minutes.

CHEST gratefully acknowledges the following founding supporters of the First 5 Minutes^™: Amgen, AstraZeneca, Bexar County, Novartis, Regeneron, Sanofi, and VIATRIS.
 

Making medicine a more inclusive practice

In February 2022, the American College of Chest Physicians (CHEST), the American Thoracic Society (ATS), and the American Lung Association announced a partnership with the prestigious Harold Amos Medical Faculty Development Program (AMFDP), a Robert Wood Johnson Foundation initiative, to sponsor a scholar in pulmonary and critical care medicine.

The recipient of that grant, George Alba, MD, Instructor of Medicine at Harvard Medical School and Pulmonary and Critical Care Physician at Massachusetts General, was announced earlier this year. Through his AMFDP award project, “Pulmonary Endothelial NEDD9 and Acute Lung Injury,” Dr. Alba seeks to advance NEDD9 antagonism as a potential therapeutic target in acute respiratory distress syndrome (ARDS).

“Growing up, I saw through my father’s example how education unlocks opportunities. Our community came together to help him on this path. Now a retired doctor of osteopathy in neonatology, it inspired me to pursue a career in medicine,” said Dr. Alba. “This award comes at a critical time in my junior faculty career: it allows me to continue pursuing my research in a meaningful way while also gaining new skills that will be critical for my ongoing career development.”

Visit bit.ly/3X4VphB to learn more about the AMFDP initiative and Dr. Alba.
 

Fun and fellowship – for a good cause

In addition, to all of this, the CHEST Foundation continued to host engaging events throughout the year to encourage connection, raise awareness, and fundraise for important initiatives.

This included the annual Belmont Stakes Dinner and Auction on June 11 in New York City. The fun-filled evening included a viewing of the 154th running of “The Championship Track,” a cocktail reception and plated dinner, a silent auction, a rooftop party, and insights from two patient advocates who turned their own experiences of living with chronic lung disease into incredible action on behalf of patients.

Three virtual wine nights in April, August, and December also invited numerous guests to learn more about imbibes from France, Italy, and California. Led by CHEST’s own resident wine aficionado, CEO Bob Musacchio, PhD, these events benefited the AMFDP, as well as other initiatives to improve patient care.

Another event that brought support to battling lung disease was the 9th Annual Irv Feldman Texas Hold 'Em Poker Tournament and Casino night jointly hosted by the Feldman Family Foundation and the CHEST Foundation. For the first time since early 2020, the event was held in-person after years of virtual tournaments. Funds raised from the event support education and resources to provide for a better quality of life for patients battling pulmonary fibrosis, a fibrotic lung disease with no cure.

2022 is special in another way. This year, the CHEST Foundation is offering an unmatched opportunity to one donor to attend CHEST 2023 in Honolulu, Hawai‘i for free. For every $250 you donate to the CHEST Foundation by December 31, 2022, you will receive an entry into a drawing for free registration, airfare (US only), and hotel accommodations.

Learn more about how you can donate to support initiatives like these – and make your mark on the practice of pulmonary, critical care, and sleep medicine – at foundation.chestnet.org.
 

Twenty-five years of life-changing grants

In addition to all of this, the CHEST Foundation provides financial grants to advance medicine and support to those in need. More than 12 million dollars later, the CHEST Foundation is proud to bolster the field of medicine and enhance patient care through this support. Learn more about the impact of grants from recent recipients in the September issue of CHEST Physician.

NEW ORLEANS – A novel, off-the-shelf antibody, talquetamab, has shown high response rates among patients with heavily pretreated multiple myeloma in both phase 1 and now phase 2 studies, which have been submitted for approval.

“Talquetamab is a novel agent directed against a new antigen target in myeloma,” explained lead investigator Ajai Chari, MD, of Icahn School of Medicine at Mount Sinai in New York.

The product has demonstrated “a response rate of 73% to 74% with both weekly and every 2-week schedules in a heavily treated patient population. Even in those patients with prior T-cell redirection, we see a 63% response rate,” said Dr. Chari, who reported the data at the American Society of Hematology annual meeting.

It is encouraging to see high response rates among patients with disease that is refractory to multiple prior lines of therapy, and the results suggest that talquetamab may buy time for patients with few other options, said Stephanie Lee, MD, MPH, of the Fred Hutchinson Cancer Center in Seattle, and a former ASH president.

“It looks like there are responses even in people who are heavily pretreated and have had other agents similar to it, “ she said. “We hear about ‘penta-refractory’ [disease] and everything, and I think we’re going to start hearing about ‘octo-refractory’ and ‘deci-refractory,’ and those things. It’s really exciting [to see these responses],” she said. Dr. Lee moderated a media briefing prior to Dr. Chari’s discussion of the data.

Talquetamab is a bispecific antibody directed against a novel target with the prosaic name of “G protein–coupled receptor, family C, group 5, member D” or simply GPRC5D. The antigen is a so-called “orphan” receptor with an unidentified ligand. The receptor is expressed in malignant plasma cells, making it a particularly attractive target for the treatment of patients with multiple myeloma.

“It’s important to pick the right target for these [patients] and GPRC5D is a good candidate for that because it’s highly expressed on myeloma cells but spares normal tissues, in particular the hematopoietic stem cells for the precursors to their blood,” Dr. Chari said.

The new drug could be available next year. The manufacturer, Janssen, announced last week that it had submitted an approval application with the Food and Drug Administration for talquetamab use in the treatment of patients with relapsed or refractory multiple myeloma.

The clinical results so far “indicate the potential of this treatment for heavily pretreated patients who have exhausted currently approved therapies,” Dr. Chari said in a statement.
 

MonumenTAL study

Dr. Chari and colleagues recently reported results of the phase 1 MonumenTAL-1 study in The New England Journal of Medicine. At ASH 2022, they reported phase 2 results from the same study, including some patients carried over from phase 1, but also a subgroup of patients with prior exposure to either chimeric antigen receptor T-cell (CAR-T) therapy or other bispecific T cell-engaging antibodies.

In the phase 1 dose-escalation study published in NEJM,  the response rates among patients who had a median of six prior lines of therapy ranged from 64% to 70%. The drug was delivered in this phase at a variety of dose levels and schedules, and both intravenously and subcutaneously.
 

Three cohorts, two doses

The phase 2 study enrolled patients who had a minimum of three prior lines of therapy including a proteasome inhibitor, immunomodulating agent, and anti-CD38 antibody, and who had good-to-fair performance status.

There were three cohorts. The first cohort comprised 21 patients from phase 1 and 122 from phase 2 who received talquetamab at a dose of 0.4 mg/kg subcutaneously once weekly. These patients were allowed to have received prior therapy with an antibody-drug conjugate (ADC) targeted against B-cell maturation antigen (BCMA), but could not have received a prior T-cell redirection therapy.

The second cohort comprised 36 patients in phase 1 and 109 in phase 2 who were treated with 0.8 mg/kg subcutaneously every 2 weeks. These patients had the same prior therapy allowances and restrictions as the first cohort.

The third cohort comprised 17 patients in phase 1 plus 34 patients in phase 2 who had received either CAR T-cell receptor therapy or a different bispecific T-cell engager. These patients received either 0.4 mg/kg weekly subcutaneous talquetamab, or 0.8 mg/kg every 2 weeks.
 

Phase 2 results

The overall response rate (ORR)  among patients treated at 0.4 mg/kg weekly was 74.1%, including 23.8% stringent complete responses (sCR), 9.8% complete response (CR), 25.9% very good partial responses (VGPR) and 14.7% partial responses (PR).

The ORR among patients treated at the 0.8 mg/kg every 2 week dose was 73.1%, consisting of 20% sCR, 12.4% CR, 24,8% VGPR, and 15.9% PR.

The response rates were consistent across subgroups, including baseline International Staging System (ISS) stage III disease, baseline cytogenetic risk, number of prior therapies, degree of refractoriness to prior therapy, and prior exposure to the anti-BCMA antibody belantamab (except patients with baseline plasmacytomas).

The median durations of responses were 9.3 months and 13 months in the 0.4 and 0.8 mg/kg doses, respectively. The median duration of response was not reached among patients who had achieved a CR or better in either dosing group.
 

Safety profile

Most adverse events of grade 3 or 4 were cytopenias, including anemia, neutropenia, lymphopenia, and thrombocytopenia. These adverse events were generally limited to the first three cycles, and less than a third of all cytopenias were grade 3 or greater.

Infection occurred in 57.3% of patients treated at 0.4 mg/kg weekly and 50.3% treated at 0.8 mg/kg every 2 weeks. Of these infections, 16.8% and 11.7%, respectively, were grade 3 or 4.

Opportunistic infections were seen in 3.5% of patients treated at 0.4 mg/kg and 2.8% of those treated at 0.8 mg/kg.

Taste alterations (dysgeusia) occurred in nearly half of patients in each dosing group. Dysgeusia was managed with supportive care, including hydration, and in some cases  with dose reductions.

Immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in 10% to 11% of patients, but most of these events were grade 1 or 2.
 

What’s next?

At the briefing, this news organization asked Dr. Chari whether, given the evident efficacy and relative safety of this agent, it could be moved up higher in the therapeutic lines and combined with other agents such as proteasome inhibitors (bortezomib et al.), immunomodulators (lenalidomide and others) and CD38-directed antibodies (daratumumab, etc.)

Dr. Chari replied that several studies combining talquetamab with agents in all of these classes and with other bispecific T-cell engagers are currently underway.

Dr. Chari disclosed consulting fees from Janssen, which supported the study. Dr. Lee has received clinical trial research funding from Amgen, AstraZeneca, Incyte, Kadmon, Novartis, Pfizer, Syndax, and Takeda and has served as a consultant to Incyte.

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

NEW ORLEANS – A novel, off-the-shelf antibody, talquetamab, has shown high response rates among patients with heavily pretreated multiple myeloma in both phase 1 and now phase 2 studies, which have been submitted for approval.

“Talquetamab is a novel agent directed against a new antigen target in myeloma,” explained lead investigator Ajai Chari, MD, of Icahn School of Medicine at Mount Sinai in New York.

The product has demonstrated “a response rate of 73% to 74% with both weekly and every 2-week schedules in a heavily treated patient population. Even in those patients with prior T-cell redirection, we see a 63% response rate,” said Dr. Chari, who reported the data at the American Society of Hematology annual meeting.

It is encouraging to see high response rates among patients with disease that is refractory to multiple prior lines of therapy, and the results suggest that talquetamab may buy time for patients with few other options, said Stephanie Lee, MD, MPH, of the Fred Hutchinson Cancer Center in Seattle, and a former ASH president.

“It looks like there are responses even in people who are heavily pretreated and have had other agents similar to it, “ she said. “We hear about ‘penta-refractory’ [disease] and everything, and I think we’re going to start hearing about ‘octo-refractory’ and ‘deci-refractory,’ and those things. It’s really exciting [to see these responses],” she said. Dr. Lee moderated a media briefing prior to Dr. Chari’s discussion of the data.

Talquetamab is a bispecific antibody directed against a novel target with the prosaic name of “G protein–coupled receptor, family C, group 5, member D” or simply GPRC5D. The antigen is a so-called “orphan” receptor with an unidentified ligand. The receptor is expressed in malignant plasma cells, making it a particularly attractive target for the treatment of patients with multiple myeloma.

“It’s important to pick the right target for these [patients] and GPRC5D is a good candidate for that because it’s highly expressed on myeloma cells but spares normal tissues, in particular the hematopoietic stem cells for the precursors to their blood,” Dr. Chari said.

The new drug could be available next year. The manufacturer, Janssen, announced last week that it had submitted an approval application with the Food and Drug Administration for talquetamab use in the treatment of patients with relapsed or refractory multiple myeloma.

The clinical results so far “indicate the potential of this treatment for heavily pretreated patients who have exhausted currently approved therapies,” Dr. Chari said in a statement.
 

MonumenTAL study

Dr. Chari and colleagues recently reported results of the phase 1 MonumenTAL-1 study in The New England Journal of Medicine. At ASH 2022, they reported phase 2 results from the same study, including some patients carried over from phase 1, but also a subgroup of patients with prior exposure to either chimeric antigen receptor T-cell (CAR-T) therapy or other bispecific T cell-engaging antibodies.

In the phase 1 dose-escalation study published in NEJM,  the response rates among patients who had a median of six prior lines of therapy ranged from 64% to 70%. The drug was delivered in this phase at a variety of dose levels and schedules, and both intravenously and subcutaneously.
 

Three cohorts, two doses

The phase 2 study enrolled patients who had a minimum of three prior lines of therapy including a proteasome inhibitor, immunomodulating agent, and anti-CD38 antibody, and who had good-to-fair performance status.

There were three cohorts. The first cohort comprised 21 patients from phase 1 and 122 from phase 2 who received talquetamab at a dose of 0.4 mg/kg subcutaneously once weekly. These patients were allowed to have received prior therapy with an antibody-drug conjugate (ADC) targeted against B-cell maturation antigen (BCMA), but could not have received a prior T-cell redirection therapy.

The second cohort comprised 36 patients in phase 1 and 109 in phase 2 who were treated with 0.8 mg/kg subcutaneously every 2 weeks. These patients had the same prior therapy allowances and restrictions as the first cohort.

The third cohort comprised 17 patients in phase 1 plus 34 patients in phase 2 who had received either CAR T-cell receptor therapy or a different bispecific T-cell engager. These patients received either 0.4 mg/kg weekly subcutaneous talquetamab, or 0.8 mg/kg every 2 weeks.
 

Phase 2 results

The overall response rate (ORR)  among patients treated at 0.4 mg/kg weekly was 74.1%, including 23.8% stringent complete responses (sCR), 9.8% complete response (CR), 25.9% very good partial responses (VGPR) and 14.7% partial responses (PR).

The ORR among patients treated at the 0.8 mg/kg every 2 week dose was 73.1%, consisting of 20% sCR, 12.4% CR, 24,8% VGPR, and 15.9% PR.

The response rates were consistent across subgroups, including baseline International Staging System (ISS) stage III disease, baseline cytogenetic risk, number of prior therapies, degree of refractoriness to prior therapy, and prior exposure to the anti-BCMA antibody belantamab (except patients with baseline plasmacytomas).

The median durations of responses were 9.3 months and 13 months in the 0.4 and 0.8 mg/kg doses, respectively. The median duration of response was not reached among patients who had achieved a CR or better in either dosing group.
 

Safety profile

Most adverse events of grade 3 or 4 were cytopenias, including anemia, neutropenia, lymphopenia, and thrombocytopenia. These adverse events were generally limited to the first three cycles, and less than a third of all cytopenias were grade 3 or greater.

Infection occurred in 57.3% of patients treated at 0.4 mg/kg weekly and 50.3% treated at 0.8 mg/kg every 2 weeks. Of these infections, 16.8% and 11.7%, respectively, were grade 3 or 4.

Opportunistic infections were seen in 3.5% of patients treated at 0.4 mg/kg and 2.8% of those treated at 0.8 mg/kg.

Taste alterations (dysgeusia) occurred in nearly half of patients in each dosing group. Dysgeusia was managed with supportive care, including hydration, and in some cases  with dose reductions.

Immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in 10% to 11% of patients, but most of these events were grade 1 or 2.
 

What’s next?

At the briefing, this news organization asked Dr. Chari whether, given the evident efficacy and relative safety of this agent, it could be moved up higher in the therapeutic lines and combined with other agents such as proteasome inhibitors (bortezomib et al.), immunomodulators (lenalidomide and others) and CD38-directed antibodies (daratumumab, etc.)

Dr. Chari replied that several studies combining talquetamab with agents in all of these classes and with other bispecific T-cell engagers are currently underway.

Dr. Chari disclosed consulting fees from Janssen, which supported the study. Dr. Lee has received clinical trial research funding from Amgen, AstraZeneca, Incyte, Kadmon, Novartis, Pfizer, Syndax, and Takeda and has served as a consultant to Incyte.

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

NEW ORLEANS – A novel, off-the-shelf antibody, talquetamab, has shown high response rates among patients with heavily pretreated multiple myeloma in both phase 1 and now phase 2 studies, which have been submitted for approval.

“Talquetamab is a novel agent directed against a new antigen target in myeloma,” explained lead investigator Ajai Chari, MD, of Icahn School of Medicine at Mount Sinai in New York.

The product has demonstrated “a response rate of 73% to 74% with both weekly and every 2-week schedules in a heavily treated patient population. Even in those patients with prior T-cell redirection, we see a 63% response rate,” said Dr. Chari, who reported the data at the American Society of Hematology annual meeting.

It is encouraging to see high response rates among patients with disease that is refractory to multiple prior lines of therapy, and the results suggest that talquetamab may buy time for patients with few other options, said Stephanie Lee, MD, MPH, of the Fred Hutchinson Cancer Center in Seattle, and a former ASH president.

“It looks like there are responses even in people who are heavily pretreated and have had other agents similar to it, “ she said. “We hear about ‘penta-refractory’ [disease] and everything, and I think we’re going to start hearing about ‘octo-refractory’ and ‘deci-refractory,’ and those things. It’s really exciting [to see these responses],” she said. Dr. Lee moderated a media briefing prior to Dr. Chari’s discussion of the data.

Talquetamab is a bispecific antibody directed against a novel target with the prosaic name of “G protein–coupled receptor, family C, group 5, member D” or simply GPRC5D. The antigen is a so-called “orphan” receptor with an unidentified ligand. The receptor is expressed in malignant plasma cells, making it a particularly attractive target for the treatment of patients with multiple myeloma.

“It’s important to pick the right target for these [patients] and GPRC5D is a good candidate for that because it’s highly expressed on myeloma cells but spares normal tissues, in particular the hematopoietic stem cells for the precursors to their blood,” Dr. Chari said.

The new drug could be available next year. The manufacturer, Janssen, announced last week that it had submitted an approval application with the Food and Drug Administration for talquetamab use in the treatment of patients with relapsed or refractory multiple myeloma.

The clinical results so far “indicate the potential of this treatment for heavily pretreated patients who have exhausted currently approved therapies,” Dr. Chari said in a statement.
 

MonumenTAL study

Dr. Chari and colleagues recently reported results of the phase 1 MonumenTAL-1 study in The New England Journal of Medicine. At ASH 2022, they reported phase 2 results from the same study, including some patients carried over from phase 1, but also a subgroup of patients with prior exposure to either chimeric antigen receptor T-cell (CAR-T) therapy or other bispecific T cell-engaging antibodies.

In the phase 1 dose-escalation study published in NEJM,  the response rates among patients who had a median of six prior lines of therapy ranged from 64% to 70%. The drug was delivered in this phase at a variety of dose levels and schedules, and both intravenously and subcutaneously.
 

Three cohorts, two doses

The phase 2 study enrolled patients who had a minimum of three prior lines of therapy including a proteasome inhibitor, immunomodulating agent, and anti-CD38 antibody, and who had good-to-fair performance status.

There were three cohorts. The first cohort comprised 21 patients from phase 1 and 122 from phase 2 who received talquetamab at a dose of 0.4 mg/kg subcutaneously once weekly. These patients were allowed to have received prior therapy with an antibody-drug conjugate (ADC) targeted against B-cell maturation antigen (BCMA), but could not have received a prior T-cell redirection therapy.

The second cohort comprised 36 patients in phase 1 and 109 in phase 2 who were treated with 0.8 mg/kg subcutaneously every 2 weeks. These patients had the same prior therapy allowances and restrictions as the first cohort.

The third cohort comprised 17 patients in phase 1 plus 34 patients in phase 2 who had received either CAR T-cell receptor therapy or a different bispecific T-cell engager. These patients received either 0.4 mg/kg weekly subcutaneous talquetamab, or 0.8 mg/kg every 2 weeks.
 

Phase 2 results

The overall response rate (ORR)  among patients treated at 0.4 mg/kg weekly was 74.1%, including 23.8% stringent complete responses (sCR), 9.8% complete response (CR), 25.9% very good partial responses (VGPR) and 14.7% partial responses (PR).

The ORR among patients treated at the 0.8 mg/kg every 2 week dose was 73.1%, consisting of 20% sCR, 12.4% CR, 24,8% VGPR, and 15.9% PR.

The response rates were consistent across subgroups, including baseline International Staging System (ISS) stage III disease, baseline cytogenetic risk, number of prior therapies, degree of refractoriness to prior therapy, and prior exposure to the anti-BCMA antibody belantamab (except patients with baseline plasmacytomas).

The median durations of responses were 9.3 months and 13 months in the 0.4 and 0.8 mg/kg doses, respectively. The median duration of response was not reached among patients who had achieved a CR or better in either dosing group.
 

Safety profile

Most adverse events of grade 3 or 4 were cytopenias, including anemia, neutropenia, lymphopenia, and thrombocytopenia. These adverse events were generally limited to the first three cycles, and less than a third of all cytopenias were grade 3 or greater.

Infection occurred in 57.3% of patients treated at 0.4 mg/kg weekly and 50.3% treated at 0.8 mg/kg every 2 weeks. Of these infections, 16.8% and 11.7%, respectively, were grade 3 or 4.

Opportunistic infections were seen in 3.5% of patients treated at 0.4 mg/kg and 2.8% of those treated at 0.8 mg/kg.

Taste alterations (dysgeusia) occurred in nearly half of patients in each dosing group. Dysgeusia was managed with supportive care, including hydration, and in some cases  with dose reductions.

Immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in 10% to 11% of patients, but most of these events were grade 1 or 2.
 

What’s next?

At the briefing, this news organization asked Dr. Chari whether, given the evident efficacy and relative safety of this agent, it could be moved up higher in the therapeutic lines and combined with other agents such as proteasome inhibitors (bortezomib et al.), immunomodulators (lenalidomide and others) and CD38-directed antibodies (daratumumab, etc.)

Dr. Chari replied that several studies combining talquetamab with agents in all of these classes and with other bispecific T-cell engagers are currently underway.

Dr. Chari disclosed consulting fees from Janssen, which supported the study. Dr. Lee has received clinical trial research funding from Amgen, AstraZeneca, Incyte, Kadmon, Novartis, Pfizer, Syndax, and Takeda and has served as a consultant to Incyte.

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

NEW ORLEANS – A gene therapy made headlines recently for becoming the most expensive pharmaceutical ever launched – the price tag was $3.5 million for a one-off treatment with etranacogene dezaparvovec (Hemgenix) for hemophilia B.

Another gene therapy, a treatment for sickle cell anemia now in late clinical development, is expected to come on the market soon. It, too, is expected to bear an exorbitant price tag.

Such potentially curative therapies put financial pressure on publicly and privately funded health insurance.

However, investigators said that the new treatment for patients with sickle cell disease (SCD) in the United States has the potential to be cost-effective. Those who analyzed the costs used a novel method that takes historical health inequities into account.

“When faced with costs of innovative, one-time-administered therapies, budgetary constraints, as we all know too well, can and have driven therapy availability or lack thereof for patients,” said George Goshua, MD, from the Yale University, New Haven, Conn., speaking here at the annual meeting of the American Society of Hematology.

“We believe that quantitative consideration of health inequities, in addition to the important quality considerations, may be an additional helpful metric in this decision-making context,” he said.

He noted that SCD predominantly affects Black Americans, “who have historically been a very marginalized population when it comes to health care.

“Our study shows that, when we compare the costs of gene therapy and existing standard-of-care treatment for SCD using a technique that accounts for historical health disparities, gene therapy could be an equitable therapeutic strategy for all patients with SCD, whether their disease is mild, moderate, or severe,” he said.

Commenting on the study for this news organization, Bosula Oluwole, MD, from the University of Washington, Seattle, who studies sickle cell disease but was not involved in this study, said the cost-analysis approach taken by Dr. Goshua and colleagues is interesting, but she added: “I think we still have a way to go in trying to fully understand the issue.

“When you look over time at the cost for a patient to get gene therapy vs. the standard of care, it might actually be beneficial to have the gene therapy,” Dr. Oluwole said.

She noted, however, that some patients start gene therapy for SCD at older ages and that it’s important to analyze whether the treatment can still be cost-effective or the best therapeutic option for such patients.
 

Adding a D to CEA

Dr. Goshua and colleagues at Yale University and the Harvard T.H. Chan School of Public Health in Boston conducted what they believe is the first study in hematology to use distributional cost-effectiveness analysis (DCEA), developed at the University of York, England.

A University of York website explains that DCEA “is a general umbrella term for economic evaluation studies that provide information about equity in the distribution of costs and effects as well as efficiency in terms of aggregate costs and effects. DCEA can provide distributional breakdowns of who gains most and who bears the largest burdens (opportunity costs) by equity-relevant social variables (e.g., socioeconomic status, ethnicity, location) and disease categories (e.g., severity of illness, rarity, disability).”

The technique can also employ equity weight to evaluate trade-offs between equity and efficiency, the website says.

As Dr. Goshua put it, equity weighting is “a way of quantifying how much we prioritize health care equity.”
 

QALYs considered

Dr. Goshua and colleagues included equity weight in an analysis of 10 years of data on annual health care costs for patients with SCD who were covered by private insurance and were treated with medications (for example, hydroxyurea), antibiotics, blood transfusion, and hematopoietic stem cell transplants. Sex and the frequency of hospitalizations for acute pain crises were factors in the Markov model they created.

The model assumes that a single course of gene therapy for SCD would cost $2.1 million. The estimate was based on the cost of U.S. Food and Drug Administration–approved gene therapies, and it was assumed that the therapy would result in permanent disease remission for all patients.

In addition, the model assumed that all eligible patients in the United States with SCD who are aged 12 years and older would be offered the gene therapy.

In their base-case analysis, gene therapy starting at age 12 would yield 25.5 discounted lifetime quality-adjusted life-years (QALYs) at a cost of $2.4 million, compared with 16.0 discounted lifetime QALYs at a cost of $1.1 million for standard care.

Under traditional cost-effectiveness calculations, the upper limit of the incremental cost-effectiveness ratio (ICER) is estimated to be $100,000 per QALY. Under this scenario, the ICER of gene therapy for SCD at $144,000 per QALY would be considered by health economists or insurers to be too steep a price to pay.

However, applying equity weighting to the formula would bring the price of gene therapy into the $1.4 million to $3 million range.

Dr. Goshua acknowledged that the study is limited by the assumption that gene therapy would be a one-time cost and that patients would not need to undergo repeat therapy or treatment for relapses.

Stephanie Lee, MD, MPH, from the Fred Hutchinson Cancer Center in Seattle, and a former ASH president, who moderated a briefing the day before Dr. Goshua presented his data, recommended that he and his colleagues use their technique to explore other health inequities, such as in the care of patients with multiple myeloma.

“There’s some evidence that Black patients are not using even the agents we have as [are] some of the other groups, so there may be some distributional inequities there as well,” she said.

The study was funded by ASH and the Yale School of Medicine. Dr. Goshua, Dr. Oluwole, and Dr. Lee have disclosed no relevant financial relationships.

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

NEW ORLEANS – A gene therapy made headlines recently for becoming the most expensive pharmaceutical ever launched – the price tag was $3.5 million for a one-off treatment with etranacogene dezaparvovec (Hemgenix) for hemophilia B.

Another gene therapy, a treatment for sickle cell anemia now in late clinical development, is expected to come on the market soon. It, too, is expected to bear an exorbitant price tag.

Such potentially curative therapies put financial pressure on publicly and privately funded health insurance.

However, investigators said that the new treatment for patients with sickle cell disease (SCD) in the United States has the potential to be cost-effective. Those who analyzed the costs used a novel method that takes historical health inequities into account.

“When faced with costs of innovative, one-time-administered therapies, budgetary constraints, as we all know too well, can and have driven therapy availability or lack thereof for patients,” said George Goshua, MD, from the Yale University, New Haven, Conn., speaking here at the annual meeting of the American Society of Hematology.

“We believe that quantitative consideration of health inequities, in addition to the important quality considerations, may be an additional helpful metric in this decision-making context,” he said.

He noted that SCD predominantly affects Black Americans, “who have historically been a very marginalized population when it comes to health care.

“Our study shows that, when we compare the costs of gene therapy and existing standard-of-care treatment for SCD using a technique that accounts for historical health disparities, gene therapy could be an equitable therapeutic strategy for all patients with SCD, whether their disease is mild, moderate, or severe,” he said.

Commenting on the study for this news organization, Bosula Oluwole, MD, from the University of Washington, Seattle, who studies sickle cell disease but was not involved in this study, said the cost-analysis approach taken by Dr. Goshua and colleagues is interesting, but she added: “I think we still have a way to go in trying to fully understand the issue.

“When you look over time at the cost for a patient to get gene therapy vs. the standard of care, it might actually be beneficial to have the gene therapy,” Dr. Oluwole said.

She noted, however, that some patients start gene therapy for SCD at older ages and that it’s important to analyze whether the treatment can still be cost-effective or the best therapeutic option for such patients.
 

Adding a D to CEA

Dr. Goshua and colleagues at Yale University and the Harvard T.H. Chan School of Public Health in Boston conducted what they believe is the first study in hematology to use distributional cost-effectiveness analysis (DCEA), developed at the University of York, England.

A University of York website explains that DCEA “is a general umbrella term for economic evaluation studies that provide information about equity in the distribution of costs and effects as well as efficiency in terms of aggregate costs and effects. DCEA can provide distributional breakdowns of who gains most and who bears the largest burdens (opportunity costs) by equity-relevant social variables (e.g., socioeconomic status, ethnicity, location) and disease categories (e.g., severity of illness, rarity, disability).”

The technique can also employ equity weight to evaluate trade-offs between equity and efficiency, the website says.

As Dr. Goshua put it, equity weighting is “a way of quantifying how much we prioritize health care equity.”
 

QALYs considered

Dr. Goshua and colleagues included equity weight in an analysis of 10 years of data on annual health care costs for patients with SCD who were covered by private insurance and were treated with medications (for example, hydroxyurea), antibiotics, blood transfusion, and hematopoietic stem cell transplants. Sex and the frequency of hospitalizations for acute pain crises were factors in the Markov model they created.

The model assumes that a single course of gene therapy for SCD would cost $2.1 million. The estimate was based on the cost of U.S. Food and Drug Administration–approved gene therapies, and it was assumed that the therapy would result in permanent disease remission for all patients.

In addition, the model assumed that all eligible patients in the United States with SCD who are aged 12 years and older would be offered the gene therapy.

In their base-case analysis, gene therapy starting at age 12 would yield 25.5 discounted lifetime quality-adjusted life-years (QALYs) at a cost of $2.4 million, compared with 16.0 discounted lifetime QALYs at a cost of $1.1 million for standard care.

Under traditional cost-effectiveness calculations, the upper limit of the incremental cost-effectiveness ratio (ICER) is estimated to be $100,000 per QALY. Under this scenario, the ICER of gene therapy for SCD at $144,000 per QALY would be considered by health economists or insurers to be too steep a price to pay.

However, applying equity weighting to the formula would bring the price of gene therapy into the $1.4 million to $3 million range.

Dr. Goshua acknowledged that the study is limited by the assumption that gene therapy would be a one-time cost and that patients would not need to undergo repeat therapy or treatment for relapses.

Stephanie Lee, MD, MPH, from the Fred Hutchinson Cancer Center in Seattle, and a former ASH president, who moderated a briefing the day before Dr. Goshua presented his data, recommended that he and his colleagues use their technique to explore other health inequities, such as in the care of patients with multiple myeloma.

“There’s some evidence that Black patients are not using even the agents we have as [are] some of the other groups, so there may be some distributional inequities there as well,” she said.

The study was funded by ASH and the Yale School of Medicine. Dr. Goshua, Dr. Oluwole, and Dr. Lee have disclosed no relevant financial relationships.

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

NEW ORLEANS – A gene therapy made headlines recently for becoming the most expensive pharmaceutical ever launched – the price tag was $3.5 million for a one-off treatment with etranacogene dezaparvovec (Hemgenix) for hemophilia B.

Another gene therapy, a treatment for sickle cell anemia now in late clinical development, is expected to come on the market soon. It, too, is expected to bear an exorbitant price tag.

Such potentially curative therapies put financial pressure on publicly and privately funded health insurance.

However, investigators said that the new treatment for patients with sickle cell disease (SCD) in the United States has the potential to be cost-effective. Those who analyzed the costs used a novel method that takes historical health inequities into account.

“When faced with costs of innovative, one-time-administered therapies, budgetary constraints, as we all know too well, can and have driven therapy availability or lack thereof for patients,” said George Goshua, MD, from the Yale University, New Haven, Conn., speaking here at the annual meeting of the American Society of Hematology.

“We believe that quantitative consideration of health inequities, in addition to the important quality considerations, may be an additional helpful metric in this decision-making context,” he said.

He noted that SCD predominantly affects Black Americans, “who have historically been a very marginalized population when it comes to health care.

“Our study shows that, when we compare the costs of gene therapy and existing standard-of-care treatment for SCD using a technique that accounts for historical health disparities, gene therapy could be an equitable therapeutic strategy for all patients with SCD, whether their disease is mild, moderate, or severe,” he said.

Commenting on the study for this news organization, Bosula Oluwole, MD, from the University of Washington, Seattle, who studies sickle cell disease but was not involved in this study, said the cost-analysis approach taken by Dr. Goshua and colleagues is interesting, but she added: “I think we still have a way to go in trying to fully understand the issue.

“When you look over time at the cost for a patient to get gene therapy vs. the standard of care, it might actually be beneficial to have the gene therapy,” Dr. Oluwole said.

She noted, however, that some patients start gene therapy for SCD at older ages and that it’s important to analyze whether the treatment can still be cost-effective or the best therapeutic option for such patients.
 

Adding a D to CEA

Dr. Goshua and colleagues at Yale University and the Harvard T.H. Chan School of Public Health in Boston conducted what they believe is the first study in hematology to use distributional cost-effectiveness analysis (DCEA), developed at the University of York, England.

A University of York website explains that DCEA “is a general umbrella term for economic evaluation studies that provide information about equity in the distribution of costs and effects as well as efficiency in terms of aggregate costs and effects. DCEA can provide distributional breakdowns of who gains most and who bears the largest burdens (opportunity costs) by equity-relevant social variables (e.g., socioeconomic status, ethnicity, location) and disease categories (e.g., severity of illness, rarity, disability).”

The technique can also employ equity weight to evaluate trade-offs between equity and efficiency, the website says.

As Dr. Goshua put it, equity weighting is “a way of quantifying how much we prioritize health care equity.”
 

QALYs considered

Dr. Goshua and colleagues included equity weight in an analysis of 10 years of data on annual health care costs for patients with SCD who were covered by private insurance and were treated with medications (for example, hydroxyurea), antibiotics, blood transfusion, and hematopoietic stem cell transplants. Sex and the frequency of hospitalizations for acute pain crises were factors in the Markov model they created.

The model assumes that a single course of gene therapy for SCD would cost $2.1 million. The estimate was based on the cost of U.S. Food and Drug Administration–approved gene therapies, and it was assumed that the therapy would result in permanent disease remission for all patients.

In addition, the model assumed that all eligible patients in the United States with SCD who are aged 12 years and older would be offered the gene therapy.

In their base-case analysis, gene therapy starting at age 12 would yield 25.5 discounted lifetime quality-adjusted life-years (QALYs) at a cost of $2.4 million, compared with 16.0 discounted lifetime QALYs at a cost of $1.1 million for standard care.

Under traditional cost-effectiveness calculations, the upper limit of the incremental cost-effectiveness ratio (ICER) is estimated to be $100,000 per QALY. Under this scenario, the ICER of gene therapy for SCD at $144,000 per QALY would be considered by health economists or insurers to be too steep a price to pay.

However, applying equity weighting to the formula would bring the price of gene therapy into the $1.4 million to $3 million range.

Dr. Goshua acknowledged that the study is limited by the assumption that gene therapy would be a one-time cost and that patients would not need to undergo repeat therapy or treatment for relapses.

Stephanie Lee, MD, MPH, from the Fred Hutchinson Cancer Center in Seattle, and a former ASH president, who moderated a briefing the day before Dr. Goshua presented his data, recommended that he and his colleagues use their technique to explore other health inequities, such as in the care of patients with multiple myeloma.

“There’s some evidence that Black patients are not using even the agents we have as [are] some of the other groups, so there may be some distributional inequities there as well,” she said.

The study was funded by ASH and the Yale School of Medicine. Dr. Goshua, Dr. Oluwole, and Dr. Lee have disclosed no relevant financial relationships.

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

These hyperpigmented lesions with fine scale on the outer edges are characteristic of pityriasis versicolor, also known as tinea versicolor. These macules (or patches) are commonly found on the trunk, proximal extremities, or neck. The lesions can be hypopigmented (pityriasis versicolor alba), hyperpigmented (pityriasis versicolor nigra), or erythematous (pityriasis versicolor rubra).¹ It is common to see hyperpigmentation in people with darker skin tones, as was the case with this patient. Pityriasis versicolor is often asymptomatic, but patients may describe mild to moderate pruritis.

Pityriasis versicolor is a common fungal infection of the superficial layers of the dermis caused by Malassezia furfur.² Impaired immunity and excessive sweating are risk factors for pityriasis versicolor; other risk factors include having a family member with tinea versicolor and living in a hot, humid region.¹ Adolescents and young adults are most often affected.¹

An evoked scale sign is a helpful tool to confirm the diagnosis clinically.³ Scale will appear when you stretch the affected skin with your thumb and index finger (or you scrape the area with a scalpel blade).³ If there is doubt about the diagnosis, use a potassium hydroxide (KOH) preparation; a positive test will reveal the classic “spaghetti and meatballs” pattern.¹

Selenium sulfide 2.5%, zinc pyrithione 1%, and ketoconazole 2% shampoo are effective topical treatments. The shampoo is applied full strength to the affected skin daily for 5 to 10 minutes before it’s washed off. This can be done for 1 to 4 weeks, with longer treatment courses resulting in higher cure rates. Systemic therapy is reserved for patients with widespread infection or those who do not respond to topical treatment.⁴ It’s important to advise patients that the restoration of normal skin pigmentation can takes months.

This patient was treated with ketoconazole 2% shampoo for 3 weeks. A complete return of skin color was achieved 6 months after completion of therapy.

‌

Image courtesy of Judy Jasser, MD. Text courtesy of Judy Jasser, MD, Department of Pediatrics, and Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

These hyperpigmented lesions with fine scale on the outer edges are characteristic of pityriasis versicolor, also known as tinea versicolor. These macules (or patches) are commonly found on the trunk, proximal extremities, or neck. The lesions can be hypopigmented (pityriasis versicolor alba), hyperpigmented (pityriasis versicolor nigra), or erythematous (pityriasis versicolor rubra).¹ It is common to see hyperpigmentation in people with darker skin tones, as was the case with this patient. Pityriasis versicolor is often asymptomatic, but patients may describe mild to moderate pruritis.

Pityriasis versicolor is a common fungal infection of the superficial layers of the dermis caused by Malassezia furfur.² Impaired immunity and excessive sweating are risk factors for pityriasis versicolor; other risk factors include having a family member with tinea versicolor and living in a hot, humid region.¹ Adolescents and young adults are most often affected.¹

An evoked scale sign is a helpful tool to confirm the diagnosis clinically.³ Scale will appear when you stretch the affected skin with your thumb and index finger (or you scrape the area with a scalpel blade).³ If there is doubt about the diagnosis, use a potassium hydroxide (KOH) preparation; a positive test will reveal the classic “spaghetti and meatballs” pattern.¹

Selenium sulfide 2.5%, zinc pyrithione 1%, and ketoconazole 2% shampoo are effective topical treatments. The shampoo is applied full strength to the affected skin daily for 5 to 10 minutes before it’s washed off. This can be done for 1 to 4 weeks, with longer treatment courses resulting in higher cure rates. Systemic therapy is reserved for patients with widespread infection or those who do not respond to topical treatment.⁴ It’s important to advise patients that the restoration of normal skin pigmentation can takes months.

This patient was treated with ketoconazole 2% shampoo for 3 weeks. A complete return of skin color was achieved 6 months after completion of therapy.

‌

Image courtesy of Judy Jasser, MD. Text courtesy of Judy Jasser, MD, Department of Pediatrics, and Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

These hyperpigmented lesions with fine scale on the outer edges are characteristic of pityriasis versicolor, also known as tinea versicolor. These macules (or patches) are commonly found on the trunk, proximal extremities, or neck. The lesions can be hypopigmented (pityriasis versicolor alba), hyperpigmented (pityriasis versicolor nigra), or erythematous (pityriasis versicolor rubra).¹ It is common to see hyperpigmentation in people with darker skin tones, as was the case with this patient. Pityriasis versicolor is often asymptomatic, but patients may describe mild to moderate pruritis.

Pityriasis versicolor is a common fungal infection of the superficial layers of the dermis caused by Malassezia furfur.² Impaired immunity and excessive sweating are risk factors for pityriasis versicolor; other risk factors include having a family member with tinea versicolor and living in a hot, humid region.¹ Adolescents and young adults are most often affected.¹

An evoked scale sign is a helpful tool to confirm the diagnosis clinically.³ Scale will appear when you stretch the affected skin with your thumb and index finger (or you scrape the area with a scalpel blade).³ If there is doubt about the diagnosis, use a potassium hydroxide (KOH) preparation; a positive test will reveal the classic “spaghetti and meatballs” pattern.¹

Selenium sulfide 2.5%, zinc pyrithione 1%, and ketoconazole 2% shampoo are effective topical treatments. The shampoo is applied full strength to the affected skin daily for 5 to 10 minutes before it’s washed off. This can be done for 1 to 4 weeks, with longer treatment courses resulting in higher cure rates. Systemic therapy is reserved for patients with widespread infection or those who do not respond to topical treatment.⁴ It’s important to advise patients that the restoration of normal skin pigmentation can takes months.

This patient was treated with ketoconazole 2% shampoo for 3 weeks. A complete return of skin color was achieved 6 months after completion of therapy.

‌

Image courtesy of Judy Jasser, MD. Text courtesy of Judy Jasser, MD, Department of Pediatrics, and Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

Postpartum depression, anxiety, and posttraumatic stress disorder that persist 2-3 years after birth are associated with a dysregulated immune system that is characterized by increased inflammatory signaling, according to investigators.

These findings suggest that mental health screening for women who have given birth should continue beyond the first year post partum, reported lead author Jennifer M. Nicoloro-SantaBarbara, PhD, of Brigham and Women’s Hospital, Harvard Medical School, Boston, and colleagues.

“Delayed postpartum depression, also known as late-onset postpartum depression, can affect women up to 18 months after delivery,” the investigators wrote in the American Journal of Reproductive Immunology. “It can appear even later in some women, depending on the hormonal changes that occur after having a baby (for example, timing of weaning). However, the majority of research on maternal mental health focuses on the first year post birth, leaving a gap in research beyond 12 months post partum.”

To address this gap, the investigators enrolled 33 women who were 2-3 years post partum. Participants completed self-guided questionnaires on PTSD, depression, and anxiety, and provided blood samples for gene expression analysis.

Sixteen of the 33 women had clinically significant mood disturbances. Compared with the other participants, these 16 women had significant upregulation of genes driving inflammatory pathways and significantly reduced activation of genes associated with viral response.

“The results provide preliminary evidence of a mechanism (e.g., immune dysregulation) that might be contributing to mood disorders and bring us closer to the goal of identifying targetable biomarkers for mood disorders,” Dr. Nicoloro-SantaBarbara said in a written comment. “This work highlights the need for standardized and continual depression and anxiety screening in ob.gyn. and primary care settings that extends beyond the 6-week maternal visit and possibly beyond the first postpartum year.”
 

Findings draw skepticism

“The authors argue that mothers need to be screened for depression/anxiety longer than the first year post partum, and this is true, but it has nothing to do with their findings,” said Jennifer L. Payne, MD, an expert in reproductive psychiatry at the University of Virginia, Charlottesville.

In a written comment, she explained that the cross-sectional design makes it impossible to know whether the mood disturbances were linked with delivery at all.

“It is unclear if the depression/anxiety symptoms began after delivery or not,” Dr. Payne said. “In addition, it is unclear if the findings are causative or a result of depression/anxiety symptoms (the authors admit this in the limitations section). It is likely that the findings are not specific or even related to having delivered a child, but rather reflect a more general process related to depression/anxiety outside of the postpartum time period.”

Only prospective studies can answer these questions, she said.

Dr. Nicoloro-SantaBarbara agreed that further research is needed.

“Our findings are exciting, but still need to be replicated in larger samples with diverse women in order to make sure they generalize,” she said. “More work is needed to understand why inflammation plays a role in postpartum mental illness for some women and not others.”

The study was supported by a Cedars-Sinai Precision Health Grant, the Cousins Center for Psychoneuroimmunology, University of California, Los Angeles, and the National Institute of Mental Health. The investigators and Dr. Payne disclosed no relevant conflicts of interest.

Postpartum depression, anxiety, and posttraumatic stress disorder that persist 2-3 years after birth are associated with a dysregulated immune system that is characterized by increased inflammatory signaling, according to investigators.

These findings suggest that mental health screening for women who have given birth should continue beyond the first year post partum, reported lead author Jennifer M. Nicoloro-SantaBarbara, PhD, of Brigham and Women’s Hospital, Harvard Medical School, Boston, and colleagues.

“Delayed postpartum depression, also known as late-onset postpartum depression, can affect women up to 18 months after delivery,” the investigators wrote in the American Journal of Reproductive Immunology. “It can appear even later in some women, depending on the hormonal changes that occur after having a baby (for example, timing of weaning). However, the majority of research on maternal mental health focuses on the first year post birth, leaving a gap in research beyond 12 months post partum.”

To address this gap, the investigators enrolled 33 women who were 2-3 years post partum. Participants completed self-guided questionnaires on PTSD, depression, and anxiety, and provided blood samples for gene expression analysis.

Sixteen of the 33 women had clinically significant mood disturbances. Compared with the other participants, these 16 women had significant upregulation of genes driving inflammatory pathways and significantly reduced activation of genes associated with viral response.

“The results provide preliminary evidence of a mechanism (e.g., immune dysregulation) that might be contributing to mood disorders and bring us closer to the goal of identifying targetable biomarkers for mood disorders,” Dr. Nicoloro-SantaBarbara said in a written comment. “This work highlights the need for standardized and continual depression and anxiety screening in ob.gyn. and primary care settings that extends beyond the 6-week maternal visit and possibly beyond the first postpartum year.”
 

Findings draw skepticism

“The authors argue that mothers need to be screened for depression/anxiety longer than the first year post partum, and this is true, but it has nothing to do with their findings,” said Jennifer L. Payne, MD, an expert in reproductive psychiatry at the University of Virginia, Charlottesville.

In a written comment, she explained that the cross-sectional design makes it impossible to know whether the mood disturbances were linked with delivery at all.

“It is unclear if the depression/anxiety symptoms began after delivery or not,” Dr. Payne said. “In addition, it is unclear if the findings are causative or a result of depression/anxiety symptoms (the authors admit this in the limitations section). It is likely that the findings are not specific or even related to having delivered a child, but rather reflect a more general process related to depression/anxiety outside of the postpartum time period.”

Only prospective studies can answer these questions, she said.

Dr. Nicoloro-SantaBarbara agreed that further research is needed.

“Our findings are exciting, but still need to be replicated in larger samples with diverse women in order to make sure they generalize,” she said. “More work is needed to understand why inflammation plays a role in postpartum mental illness for some women and not others.”

The study was supported by a Cedars-Sinai Precision Health Grant, the Cousins Center for Psychoneuroimmunology, University of California, Los Angeles, and the National Institute of Mental Health. The investigators and Dr. Payne disclosed no relevant conflicts of interest.

Postpartum depression, anxiety, and posttraumatic stress disorder that persist 2-3 years after birth are associated with a dysregulated immune system that is characterized by increased inflammatory signaling, according to investigators.

These findings suggest that mental health screening for women who have given birth should continue beyond the first year post partum, reported lead author Jennifer M. Nicoloro-SantaBarbara, PhD, of Brigham and Women’s Hospital, Harvard Medical School, Boston, and colleagues.

“Delayed postpartum depression, also known as late-onset postpartum depression, can affect women up to 18 months after delivery,” the investigators wrote in the American Journal of Reproductive Immunology. “It can appear even later in some women, depending on the hormonal changes that occur after having a baby (for example, timing of weaning). However, the majority of research on maternal mental health focuses on the first year post birth, leaving a gap in research beyond 12 months post partum.”

To address this gap, the investigators enrolled 33 women who were 2-3 years post partum. Participants completed self-guided questionnaires on PTSD, depression, and anxiety, and provided blood samples for gene expression analysis.

Sixteen of the 33 women had clinically significant mood disturbances. Compared with the other participants, these 16 women had significant upregulation of genes driving inflammatory pathways and significantly reduced activation of genes associated with viral response.

“The results provide preliminary evidence of a mechanism (e.g., immune dysregulation) that might be contributing to mood disorders and bring us closer to the goal of identifying targetable biomarkers for mood disorders,” Dr. Nicoloro-SantaBarbara said in a written comment. “This work highlights the need for standardized and continual depression and anxiety screening in ob.gyn. and primary care settings that extends beyond the 6-week maternal visit and possibly beyond the first postpartum year.”
 

Findings draw skepticism

“The authors argue that mothers need to be screened for depression/anxiety longer than the first year post partum, and this is true, but it has nothing to do with their findings,” said Jennifer L. Payne, MD, an expert in reproductive psychiatry at the University of Virginia, Charlottesville.

In a written comment, she explained that the cross-sectional design makes it impossible to know whether the mood disturbances were linked with delivery at all.

“It is unclear if the depression/anxiety symptoms began after delivery or not,” Dr. Payne said. “In addition, it is unclear if the findings are causative or a result of depression/anxiety symptoms (the authors admit this in the limitations section). It is likely that the findings are not specific or even related to having delivered a child, but rather reflect a more general process related to depression/anxiety outside of the postpartum time period.”

Only prospective studies can answer these questions, she said.

Dr. Nicoloro-SantaBarbara agreed that further research is needed.

“Our findings are exciting, but still need to be replicated in larger samples with diverse women in order to make sure they generalize,” she said. “More work is needed to understand why inflammation plays a role in postpartum mental illness for some women and not others.”

The study was supported by a Cedars-Sinai Precision Health Grant, the Cousins Center for Psychoneuroimmunology, University of California, Los Angeles, and the National Institute of Mental Health. The investigators and Dr. Payne disclosed no relevant conflicts of interest.

NASHVILLE, TENN. – About 21% of teens newly diagnosed with epilepsy experience suicidal ideation, and the percentage jumps to 31% within 3 years, new research reveals.

“We hope these results inspire epileptologists and neurologists to both recognize and screen for suicide ideation and behaviors in their adolescent patients,” said study investigator Hadley Greenwood, a third-year medical student at New York University.

The new data should also encourage providers “to become more comfortable” providing support to patients, “be that by increasing their familiarity with prescribing different antidepressants or by being well versed in how to connect patients to resources within their community,” said Mr. Greenwood.

The findings were presented here at the annual meeting of the American Epilepsy Society.
 

Little research

Previous studies have reported on the prevalence of suicidality as well as depression and anxiety among adults with epilepsy. “We wanted to look at adolescents because there’s much less in the literature out there about psychiatric comorbidity, and specifically suicidality, in this population,” said Mr. Greenwood.

Researchers used data from the Human Epilepsy Project, a study that collected data from 34 sites in the United States, Canada, Europe, and Australia from 2012 to 2017.

From a cohort of more than 400 participants, researchers identified 67 patients aged 11-17 years who were enrolled within 4 months of starting treatment for focal epilepsy.

Participants completed the Columbia–Suicide Severity Rating Scale (C-SSRS) at enrollment and at follow-ups over 36 months. The C-SSRS measures suicidal ideation and severity, said Mr. Greenwood.

“It’s scaled from passive suicide ideation, such as thoughts of ‘I wish I were dead’ without active intent, all the way up to active suicidal ideation with a plan and intent.”

Researchers were able to distinguish individuals with passive suicide ideation from those with more serious intentions, said Mr. Greenwood. They used medical records to evaluate the prevalence of suicidal ideation and behavior.

The investigators found that more than one in five (20.9%) teens endorsed any lifetime suicide ideation. This, said Mr. Greenwood, is “roughly equivalent” to the prevalence reported earlier in the adult cohort of the Human Epilepsy Project (21.6%).
 

‘Striking’ rate

The fact that one in five adolescents had any lifetime suicide ideation is “definitely a striking number,” said Mr. Greenwood.

Researchers found that 15% of patients experienced active suicide ideation, 7.5% exhibited preparatory or suicidal behaviors, and 3% had made a prior suicide attempt.

All of these percentages increased at 3 years: Thirty-one percent for suicide ideation; 25% for active suicide behavior, 15% for preparatory or suicide behaviors, and 5% for prior suicide attempt.

The fact that nearly one in three adolescents endorsed suicide ideation at 3 years is another “striking” finding, said Mr. Greenwood.

Of the 53 adolescents who had never had suicide ideation at the time of enrollment, 7 endorsed new-onset suicide ideation in the follow-up period. Five of 14 who had had suicide ideation at some point prior to enrollment continued to endorse it.

“The value of the study is identifying the prevalence and identifying the significant number of adolescents with epilepsy who are endorsing either suicide ideation or suicidal behaviors,” said Mr. Greenwood.

The researchers found that among younger teens (aged 11–14 years) rates of suicide ideation were higher than among their older counterparts (aged 15–17 years).

The study does not shed light on the biological connection between epilepsy and suicidality, but Mr. Greenwood noted that prior research has suggested a bidirectional relationship.

“Depression and other psychiatric comorbidities might exist prior to epileptic activity and actually predispose to epileptic activity.”

Mr. Greenwood noted that suicide ideation has “spiked” recently across the general population, and so it’s difficult to compare the prevalence in her study with “today’s prevalence.”

However, other research generally shows that the suicide ideation rate in the general adolescent population is much lower than in teens with epilepsy.

Unique aspects of the current study are that it reports suicide ideation and behaviors at around the time of an epilepsy diagnosis and documents how suicidality progresses or resolves over time, said Mr. Greenwood.
 

Underdiagnosed, undertreated

Commenting on the research, Elizabeth Donner, MD, director of the comprehensive epilepsy program, Hospital for Sick Children, and associate professor, department of pediatrics, University of Toronto, said a “key point” from the study is that the suicidality rate among teens with epilepsy exceeds that of children not living with epilepsy.

“We are significantly underdiagnosing and undertreating the mental health comorbidities in epilepsy,” said Dr. Donner. “Epilepsy is a brain disease and so are mental health disorders, so it shouldn’t come as any surprise that they coexist in individuals with epilepsy.”

The new results contribute to what is already known about the significant mortality rates among persons with epilepsy, said Dr. Donner. She referred to a 2018 study that showed that people with epilepsy were 3.5 times more likely to die by suicide.

Other research has shown that people with epilepsy are 10 times more likely to die by drowning, mostly in the bathtub, said Dr. Donner.

“You would think that we’re educating these people about risks related to their epilepsy, but either the messages don’t get through, or they don’t know how to keep themselves safe,” she said.

“This needs to be seen in a bigger picture, and the bigger picture is we need to recognize comorbid mental health issues; we need to address them once recognized; and then we need to counsel and support people to live safely with their epilepsy.

The study received funding from the Epilepsy Study Consortium, Finding a Cure for Epilepsy and Seizures (FACES) and other related foundations, UCB, Pfizer, Eisai, Lundbeck, and Sunovion. Mr. Greenwood and Dr. Donner report no relevant financial relationships.

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

NASHVILLE, TENN. – About 21% of teens newly diagnosed with epilepsy experience suicidal ideation, and the percentage jumps to 31% within 3 years, new research reveals.

“We hope these results inspire epileptologists and neurologists to both recognize and screen for suicide ideation and behaviors in their adolescent patients,” said study investigator Hadley Greenwood, a third-year medical student at New York University.

The new data should also encourage providers “to become more comfortable” providing support to patients, “be that by increasing their familiarity with prescribing different antidepressants or by being well versed in how to connect patients to resources within their community,” said Mr. Greenwood.

The findings were presented here at the annual meeting of the American Epilepsy Society.
 

Little research

Previous studies have reported on the prevalence of suicidality as well as depression and anxiety among adults with epilepsy. “We wanted to look at adolescents because there’s much less in the literature out there about psychiatric comorbidity, and specifically suicidality, in this population,” said Mr. Greenwood.

Researchers used data from the Human Epilepsy Project, a study that collected data from 34 sites in the United States, Canada, Europe, and Australia from 2012 to 2017.

From a cohort of more than 400 participants, researchers identified 67 patients aged 11-17 years who were enrolled within 4 months of starting treatment for focal epilepsy.

Participants completed the Columbia–Suicide Severity Rating Scale (C-SSRS) at enrollment and at follow-ups over 36 months. The C-SSRS measures suicidal ideation and severity, said Mr. Greenwood.

“It’s scaled from passive suicide ideation, such as thoughts of ‘I wish I were dead’ without active intent, all the way up to active suicidal ideation with a plan and intent.”

Researchers were able to distinguish individuals with passive suicide ideation from those with more serious intentions, said Mr. Greenwood. They used medical records to evaluate the prevalence of suicidal ideation and behavior.

The investigators found that more than one in five (20.9%) teens endorsed any lifetime suicide ideation. This, said Mr. Greenwood, is “roughly equivalent” to the prevalence reported earlier in the adult cohort of the Human Epilepsy Project (21.6%).
 

‘Striking’ rate

The fact that one in five adolescents had any lifetime suicide ideation is “definitely a striking number,” said Mr. Greenwood.

Researchers found that 15% of patients experienced active suicide ideation, 7.5% exhibited preparatory or suicidal behaviors, and 3% had made a prior suicide attempt.

All of these percentages increased at 3 years: Thirty-one percent for suicide ideation; 25% for active suicide behavior, 15% for preparatory or suicide behaviors, and 5% for prior suicide attempt.

The fact that nearly one in three adolescents endorsed suicide ideation at 3 years is another “striking” finding, said Mr. Greenwood.

Of the 53 adolescents who had never had suicide ideation at the time of enrollment, 7 endorsed new-onset suicide ideation in the follow-up period. Five of 14 who had had suicide ideation at some point prior to enrollment continued to endorse it.

“The value of the study is identifying the prevalence and identifying the significant number of adolescents with epilepsy who are endorsing either suicide ideation or suicidal behaviors,” said Mr. Greenwood.

The researchers found that among younger teens (aged 11–14 years) rates of suicide ideation were higher than among their older counterparts (aged 15–17 years).

The study does not shed light on the biological connection between epilepsy and suicidality, but Mr. Greenwood noted that prior research has suggested a bidirectional relationship.

“Depression and other psychiatric comorbidities might exist prior to epileptic activity and actually predispose to epileptic activity.”

Mr. Greenwood noted that suicide ideation has “spiked” recently across the general population, and so it’s difficult to compare the prevalence in her study with “today’s prevalence.”

However, other research generally shows that the suicide ideation rate in the general adolescent population is much lower than in teens with epilepsy.

Unique aspects of the current study are that it reports suicide ideation and behaviors at around the time of an epilepsy diagnosis and documents how suicidality progresses or resolves over time, said Mr. Greenwood.
 

Underdiagnosed, undertreated

Commenting on the research, Elizabeth Donner, MD, director of the comprehensive epilepsy program, Hospital for Sick Children, and associate professor, department of pediatrics, University of Toronto, said a “key point” from the study is that the suicidality rate among teens with epilepsy exceeds that of children not living with epilepsy.

“We are significantly underdiagnosing and undertreating the mental health comorbidities in epilepsy,” said Dr. Donner. “Epilepsy is a brain disease and so are mental health disorders, so it shouldn’t come as any surprise that they coexist in individuals with epilepsy.”

The new results contribute to what is already known about the significant mortality rates among persons with epilepsy, said Dr. Donner. She referred to a 2018 study that showed that people with epilepsy were 3.5 times more likely to die by suicide.

Other research has shown that people with epilepsy are 10 times more likely to die by drowning, mostly in the bathtub, said Dr. Donner.

“You would think that we’re educating these people about risks related to their epilepsy, but either the messages don’t get through, or they don’t know how to keep themselves safe,” she said.

“This needs to be seen in a bigger picture, and the bigger picture is we need to recognize comorbid mental health issues; we need to address them once recognized; and then we need to counsel and support people to live safely with their epilepsy.

The study received funding from the Epilepsy Study Consortium, Finding a Cure for Epilepsy and Seizures (FACES) and other related foundations, UCB, Pfizer, Eisai, Lundbeck, and Sunovion. Mr. Greenwood and Dr. Donner report no relevant financial relationships.

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

NASHVILLE, TENN. – About 21% of teens newly diagnosed with epilepsy experience suicidal ideation, and the percentage jumps to 31% within 3 years, new research reveals.

“We hope these results inspire epileptologists and neurologists to both recognize and screen for suicide ideation and behaviors in their adolescent patients,” said study investigator Hadley Greenwood, a third-year medical student at New York University.

The new data should also encourage providers “to become more comfortable” providing support to patients, “be that by increasing their familiarity with prescribing different antidepressants or by being well versed in how to connect patients to resources within their community,” said Mr. Greenwood.

The findings were presented here at the annual meeting of the American Epilepsy Society.
 

Little research

Previous studies have reported on the prevalence of suicidality as well as depression and anxiety among adults with epilepsy. “We wanted to look at adolescents because there’s much less in the literature out there about psychiatric comorbidity, and specifically suicidality, in this population,” said Mr. Greenwood.

Researchers used data from the Human Epilepsy Project, a study that collected data from 34 sites in the United States, Canada, Europe, and Australia from 2012 to 2017.

From a cohort of more than 400 participants, researchers identified 67 patients aged 11-17 years who were enrolled within 4 months of starting treatment for focal epilepsy.

Participants completed the Columbia–Suicide Severity Rating Scale (C-SSRS) at enrollment and at follow-ups over 36 months. The C-SSRS measures suicidal ideation and severity, said Mr. Greenwood.

“It’s scaled from passive suicide ideation, such as thoughts of ‘I wish I were dead’ without active intent, all the way up to active suicidal ideation with a plan and intent.”

Researchers were able to distinguish individuals with passive suicide ideation from those with more serious intentions, said Mr. Greenwood. They used medical records to evaluate the prevalence of suicidal ideation and behavior.

The investigators found that more than one in five (20.9%) teens endorsed any lifetime suicide ideation. This, said Mr. Greenwood, is “roughly equivalent” to the prevalence reported earlier in the adult cohort of the Human Epilepsy Project (21.6%).
 

‘Striking’ rate

The fact that one in five adolescents had any lifetime suicide ideation is “definitely a striking number,” said Mr. Greenwood.

Researchers found that 15% of patients experienced active suicide ideation, 7.5% exhibited preparatory or suicidal behaviors, and 3% had made a prior suicide attempt.

All of these percentages increased at 3 years: Thirty-one percent for suicide ideation; 25% for active suicide behavior, 15% for preparatory or suicide behaviors, and 5% for prior suicide attempt.

The fact that nearly one in three adolescents endorsed suicide ideation at 3 years is another “striking” finding, said Mr. Greenwood.

Of the 53 adolescents who had never had suicide ideation at the time of enrollment, 7 endorsed new-onset suicide ideation in the follow-up period. Five of 14 who had had suicide ideation at some point prior to enrollment continued to endorse it.

“The value of the study is identifying the prevalence and identifying the significant number of adolescents with epilepsy who are endorsing either suicide ideation or suicidal behaviors,” said Mr. Greenwood.

The researchers found that among younger teens (aged 11–14 years) rates of suicide ideation were higher than among their older counterparts (aged 15–17 years).

The study does not shed light on the biological connection between epilepsy and suicidality, but Mr. Greenwood noted that prior research has suggested a bidirectional relationship.

“Depression and other psychiatric comorbidities might exist prior to epileptic activity and actually predispose to epileptic activity.”

Mr. Greenwood noted that suicide ideation has “spiked” recently across the general population, and so it’s difficult to compare the prevalence in her study with “today’s prevalence.”

However, other research generally shows that the suicide ideation rate in the general adolescent population is much lower than in teens with epilepsy.

Unique aspects of the current study are that it reports suicide ideation and behaviors at around the time of an epilepsy diagnosis and documents how suicidality progresses or resolves over time, said Mr. Greenwood.
 

Underdiagnosed, undertreated

Commenting on the research, Elizabeth Donner, MD, director of the comprehensive epilepsy program, Hospital for Sick Children, and associate professor, department of pediatrics, University of Toronto, said a “key point” from the study is that the suicidality rate among teens with epilepsy exceeds that of children not living with epilepsy.

“We are significantly underdiagnosing and undertreating the mental health comorbidities in epilepsy,” said Dr. Donner. “Epilepsy is a brain disease and so are mental health disorders, so it shouldn’t come as any surprise that they coexist in individuals with epilepsy.”

The new results contribute to what is already known about the significant mortality rates among persons with epilepsy, said Dr. Donner. She referred to a 2018 study that showed that people with epilepsy were 3.5 times more likely to die by suicide.

Other research has shown that people with epilepsy are 10 times more likely to die by drowning, mostly in the bathtub, said Dr. Donner.

“You would think that we’re educating these people about risks related to their epilepsy, but either the messages don’t get through, or they don’t know how to keep themselves safe,” she said.

“This needs to be seen in a bigger picture, and the bigger picture is we need to recognize comorbid mental health issues; we need to address them once recognized; and then we need to counsel and support people to live safely with their epilepsy.

The study received funding from the Epilepsy Study Consortium, Finding a Cure for Epilepsy and Seizures (FACES) and other related foundations, UCB, Pfizer, Eisai, Lundbeck, and Sunovion. Mr. Greenwood and Dr. Donner report no relevant financial relationships.

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

NASHVILLE, Tenn. – New research shows stark racial and ethnic discrepancies in health care outcomes for patients with status epilepticus. Investigators found that among Black patients with status epilepticus, the hospitalization rate was twice that of their White counterparts. Other findings reveal age and income disparities.

“The results suggest that racial minorities, those with a lower income, and the elderly are an appropriate target to improve health outcomes and reduce health inequality,” said Gabriela Tantillo Sepúlveda, MD, assistant professor of neurology, Baylor College of Medicine, Houston.

The findings were presented at the annual meeting of the American Epilepsy Society.
 

An examination of outcomes

Status epilepticus is associated with high rates of morbidity and mortality. Disparities in epilepsy care have previously been described, but little attention has been paid to the contribution of disparities to status epilepticus care and associated outcomes.

Researchers used 2010-2019 data from the Nationwide Inpatient Sample, a database covering a cross-section of hospitalizations in 48 states and the District of Columbia. From relevant diagnostic codes, they calculated status epilepticus prevalence as the rate per 10,000 hospitalizations and stratified this by demographics.

Over the study period, investigators identified 486,861 status epilepticus hospitalizations, most (71.3%) at urban teaching hospitals.

Status epilepticus prevalence was highest for non-Hispanic Black patients, at 27.3, followed by non-Hispanic others, at 16.1, Hispanic patients, at 15.8, and non-Hispanic-White patients, at 13.7 (P < .01).

The finding that Black patients had double the rate as White patients was “definitely surprising,” said Dr. Tantillo Sepúlveda.

Research over the past 20 years revealed similar disparities related to status epilepticus, “so it’s upsetting that these disparities have persisted. Unfortunately, we still have a lot of work to do to reduce health inequalities,” she said.

The investigators found that the prevalence of status epilepticus was higher in the lowest-income quartile, compared with the highest (18.7 vs. 14; P < .01).
 

Need for physician advocacy

Unlike previous studies, this research assessed various interventions in different age groups and showed that the likelihood of intubation, tracheostomy, gastrostomy, and in-hospital mortality increased with age.

For example, compared with the reference group (patients aged 18-39 years), the odds of intubation were 1.22 (95% confidence interval, 1.16-1.27) for those aged 40-59 years and 1.48 (95% CI, 1.42-1.54) for those aged 60-79. Those aged 80 and older were most likely to be intubated, at an odds ratio of 1.5 (95% CI, 1.43-1.58).

Elderly patients were most likely to undergo tracheostomy (OR, 2.0; 95% CI, 1.75-2.27), gastrostomy (OR, 3.37; 95% CI, 2.97-3.83), and to experience in-hospital mortality (OR, 6.51; 95% CI, 5.95-7.13), compared with the youngest patients.

These intervention rates also varied by racial/ethnic groups. Minority populations, particularly Black people, had higher odds of tracheostomy and gastrostomy, compared with non-Hispanic White persons.

The odds of undergoing electroencephalography monitoring progressively rose as income level increased (OR, 1.47; 95% CI, 1.34-1.62) for the highest income quartile versus the lowest quartile. The odds of undergoing EEG monitoring were also higher at urban teaching hospitals than at rural hospitals.

Tackling these disparities in this patient population include increasing resources, personnel, and health education aimed at minorities, low-income patients, and the elderly, said Dr. Tantillo Sepúlveda. She added that more research is needed “to determine the most effective ways of accomplishing this goal.”

The medical community can help reduce disparities, said Dr. Tantillo Sepúlveda, by working to improve health literacy, to reduce stigma associated with seizures, and to increase awareness of seizure risk factors.

They can also work to expand access to outpatient neurology clinics, epilepsy monitoring units, and epilepsy surgery. “Ethnic and racial minorities are less likely to receive epilepsy surgery for temporal lobe epilepsy, which has been shown to improve quality of life and reduce seizure burden,” Dr. Tantillo Sepúlveda noted.
 

Across-the-board problem

Commenting on the research, Daniel Lowenstein, MD, professor of neurology, University of California, San Francisco, said the findings aren’t at all surprising. “It’s yet another piece of evidence on what has now become a rather voluminous literature that documents the very significant disparities that exist in our health care system,” said Dr. Lowenstein. “There’s just a huge literature on ‘name your disease and you’ll see the disparities.’ ”

Disparities exist, for example, in diagnosing breast cancer and prostate cancer, in the treatment of stroke and in related outcomes, and there is a well-documented “big disparity” in the approach to pain control among patients presenting at the emergency department, said Dr. Lowenstein.

However, he doesn’t know how disparities in epilepsy and specifically in status epilepticus, compared with disparities regarding other diseases and disorders. He noted that in the case of epilepsy, the situation is likely exacerbated by the stigma associated with that disease.

Dr. Lowenstein agreed that clinicians should play a role in reversing disparities. “We as physicians have a responsibility to be a voice for change in our health care system.”

The study was supported by the Center of Excellence for health equity, training, and research at the Baylor College of Medicine. Dr. Tantillo Sepúlveda and Dr. Lowenstein report no relevant financial relationships.

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

NASHVILLE, Tenn. – New research shows stark racial and ethnic discrepancies in health care outcomes for patients with status epilepticus. Investigators found that among Black patients with status epilepticus, the hospitalization rate was twice that of their White counterparts. Other findings reveal age and income disparities.

“The results suggest that racial minorities, those with a lower income, and the elderly are an appropriate target to improve health outcomes and reduce health inequality,” said Gabriela Tantillo Sepúlveda, MD, assistant professor of neurology, Baylor College of Medicine, Houston.

The findings were presented at the annual meeting of the American Epilepsy Society.
 

An examination of outcomes

Status epilepticus is associated with high rates of morbidity and mortality. Disparities in epilepsy care have previously been described, but little attention has been paid to the contribution of disparities to status epilepticus care and associated outcomes.

Researchers used 2010-2019 data from the Nationwide Inpatient Sample, a database covering a cross-section of hospitalizations in 48 states and the District of Columbia. From relevant diagnostic codes, they calculated status epilepticus prevalence as the rate per 10,000 hospitalizations and stratified this by demographics.

Over the study period, investigators identified 486,861 status epilepticus hospitalizations, most (71.3%) at urban teaching hospitals.

Status epilepticus prevalence was highest for non-Hispanic Black patients, at 27.3, followed by non-Hispanic others, at 16.1, Hispanic patients, at 15.8, and non-Hispanic-White patients, at 13.7 (P < .01).

The finding that Black patients had double the rate as White patients was “definitely surprising,” said Dr. Tantillo Sepúlveda.

Research over the past 20 years revealed similar disparities related to status epilepticus, “so it’s upsetting that these disparities have persisted. Unfortunately, we still have a lot of work to do to reduce health inequalities,” she said.

The investigators found that the prevalence of status epilepticus was higher in the lowest-income quartile, compared with the highest (18.7 vs. 14; P < .01).
 

Need for physician advocacy

Unlike previous studies, this research assessed various interventions in different age groups and showed that the likelihood of intubation, tracheostomy, gastrostomy, and in-hospital mortality increased with age.

For example, compared with the reference group (patients aged 18-39 years), the odds of intubation were 1.22 (95% confidence interval, 1.16-1.27) for those aged 40-59 years and 1.48 (95% CI, 1.42-1.54) for those aged 60-79. Those aged 80 and older were most likely to be intubated, at an odds ratio of 1.5 (95% CI, 1.43-1.58).

Elderly patients were most likely to undergo tracheostomy (OR, 2.0; 95% CI, 1.75-2.27), gastrostomy (OR, 3.37; 95% CI, 2.97-3.83), and to experience in-hospital mortality (OR, 6.51; 95% CI, 5.95-7.13), compared with the youngest patients.

These intervention rates also varied by racial/ethnic groups. Minority populations, particularly Black people, had higher odds of tracheostomy and gastrostomy, compared with non-Hispanic White persons.

The odds of undergoing electroencephalography monitoring progressively rose as income level increased (OR, 1.47; 95% CI, 1.34-1.62) for the highest income quartile versus the lowest quartile. The odds of undergoing EEG monitoring were also higher at urban teaching hospitals than at rural hospitals.

Tackling these disparities in this patient population include increasing resources, personnel, and health education aimed at minorities, low-income patients, and the elderly, said Dr. Tantillo Sepúlveda. She added that more research is needed “to determine the most effective ways of accomplishing this goal.”

The medical community can help reduce disparities, said Dr. Tantillo Sepúlveda, by working to improve health literacy, to reduce stigma associated with seizures, and to increase awareness of seizure risk factors.

They can also work to expand access to outpatient neurology clinics, epilepsy monitoring units, and epilepsy surgery. “Ethnic and racial minorities are less likely to receive epilepsy surgery for temporal lobe epilepsy, which has been shown to improve quality of life and reduce seizure burden,” Dr. Tantillo Sepúlveda noted.
 

Across-the-board problem

Commenting on the research, Daniel Lowenstein, MD, professor of neurology, University of California, San Francisco, said the findings aren’t at all surprising. “It’s yet another piece of evidence on what has now become a rather voluminous literature that documents the very significant disparities that exist in our health care system,” said Dr. Lowenstein. “There’s just a huge literature on ‘name your disease and you’ll see the disparities.’ ”

Disparities exist, for example, in diagnosing breast cancer and prostate cancer, in the treatment of stroke and in related outcomes, and there is a well-documented “big disparity” in the approach to pain control among patients presenting at the emergency department, said Dr. Lowenstein.

However, he doesn’t know how disparities in epilepsy and specifically in status epilepticus, compared with disparities regarding other diseases and disorders. He noted that in the case of epilepsy, the situation is likely exacerbated by the stigma associated with that disease.

Dr. Lowenstein agreed that clinicians should play a role in reversing disparities. “We as physicians have a responsibility to be a voice for change in our health care system.”

The study was supported by the Center of Excellence for health equity, training, and research at the Baylor College of Medicine. Dr. Tantillo Sepúlveda and Dr. Lowenstein report no relevant financial relationships.

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

NASHVILLE, Tenn. – New research shows stark racial and ethnic discrepancies in health care outcomes for patients with status epilepticus. Investigators found that among Black patients with status epilepticus, the hospitalization rate was twice that of their White counterparts. Other findings reveal age and income disparities.

“The results suggest that racial minorities, those with a lower income, and the elderly are an appropriate target to improve health outcomes and reduce health inequality,” said Gabriela Tantillo Sepúlveda, MD, assistant professor of neurology, Baylor College of Medicine, Houston.

The findings were presented at the annual meeting of the American Epilepsy Society.
 

An examination of outcomes

Status epilepticus is associated with high rates of morbidity and mortality. Disparities in epilepsy care have previously been described, but little attention has been paid to the contribution of disparities to status epilepticus care and associated outcomes.

Researchers used 2010-2019 data from the Nationwide Inpatient Sample, a database covering a cross-section of hospitalizations in 48 states and the District of Columbia. From relevant diagnostic codes, they calculated status epilepticus prevalence as the rate per 10,000 hospitalizations and stratified this by demographics.

Over the study period, investigators identified 486,861 status epilepticus hospitalizations, most (71.3%) at urban teaching hospitals.

Status epilepticus prevalence was highest for non-Hispanic Black patients, at 27.3, followed by non-Hispanic others, at 16.1, Hispanic patients, at 15.8, and non-Hispanic-White patients, at 13.7 (P < .01).

The finding that Black patients had double the rate as White patients was “definitely surprising,” said Dr. Tantillo Sepúlveda.

Research over the past 20 years revealed similar disparities related to status epilepticus, “so it’s upsetting that these disparities have persisted. Unfortunately, we still have a lot of work to do to reduce health inequalities,” she said.

The investigators found that the prevalence of status epilepticus was higher in the lowest-income quartile, compared with the highest (18.7 vs. 14; P < .01).
 

Need for physician advocacy

Unlike previous studies, this research assessed various interventions in different age groups and showed that the likelihood of intubation, tracheostomy, gastrostomy, and in-hospital mortality increased with age.

For example, compared with the reference group (patients aged 18-39 years), the odds of intubation were 1.22 (95% confidence interval, 1.16-1.27) for those aged 40-59 years and 1.48 (95% CI, 1.42-1.54) for those aged 60-79. Those aged 80 and older were most likely to be intubated, at an odds ratio of 1.5 (95% CI, 1.43-1.58).

Elderly patients were most likely to undergo tracheostomy (OR, 2.0; 95% CI, 1.75-2.27), gastrostomy (OR, 3.37; 95% CI, 2.97-3.83), and to experience in-hospital mortality (OR, 6.51; 95% CI, 5.95-7.13), compared with the youngest patients.

These intervention rates also varied by racial/ethnic groups. Minority populations, particularly Black people, had higher odds of tracheostomy and gastrostomy, compared with non-Hispanic White persons.

The odds of undergoing electroencephalography monitoring progressively rose as income level increased (OR, 1.47; 95% CI, 1.34-1.62) for the highest income quartile versus the lowest quartile. The odds of undergoing EEG monitoring were also higher at urban teaching hospitals than at rural hospitals.

Tackling these disparities in this patient population include increasing resources, personnel, and health education aimed at minorities, low-income patients, and the elderly, said Dr. Tantillo Sepúlveda. She added that more research is needed “to determine the most effective ways of accomplishing this goal.”

The medical community can help reduce disparities, said Dr. Tantillo Sepúlveda, by working to improve health literacy, to reduce stigma associated with seizures, and to increase awareness of seizure risk factors.

They can also work to expand access to outpatient neurology clinics, epilepsy monitoring units, and epilepsy surgery. “Ethnic and racial minorities are less likely to receive epilepsy surgery for temporal lobe epilepsy, which has been shown to improve quality of life and reduce seizure burden,” Dr. Tantillo Sepúlveda noted.
 

Across-the-board problem

Commenting on the research, Daniel Lowenstein, MD, professor of neurology, University of California, San Francisco, said the findings aren’t at all surprising. “It’s yet another piece of evidence on what has now become a rather voluminous literature that documents the very significant disparities that exist in our health care system,” said Dr. Lowenstein. “There’s just a huge literature on ‘name your disease and you’ll see the disparities.’ ”

Disparities exist, for example, in diagnosing breast cancer and prostate cancer, in the treatment of stroke and in related outcomes, and there is a well-documented “big disparity” in the approach to pain control among patients presenting at the emergency department, said Dr. Lowenstein.

However, he doesn’t know how disparities in epilepsy and specifically in status epilepticus, compared with disparities regarding other diseases and disorders. He noted that in the case of epilepsy, the situation is likely exacerbated by the stigma associated with that disease.

Dr. Lowenstein agreed that clinicians should play a role in reversing disparities. “We as physicians have a responsibility to be a voice for change in our health care system.”

The study was supported by the Center of Excellence for health equity, training, and research at the Baylor College of Medicine. Dr. Tantillo Sepúlveda and Dr. Lowenstein report no relevant financial relationships.

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