Offering shopping vouchers to pregnant women as an incentive to quit smoking showed promising results, a study found, despite most participants relapsing after giving birth.

Rewarding pregnant women with up to £400 to spend on Main Street, in addition to usual support, more than doubled the proportion who were still smoke-free late in their pregnancy, and could save the National Health Service money in the long term, according to the research, published in the BMJ, led by the University of Glasgow and the University of York, England.

Although the proportion of women in the United Kingdom who smoke during pregnancy has halved over the past 20 years, those who still do are more reluctant to engage with cessation services.

Interventions using financial incentives were pioneered in the United States, but there is a lack of evidence for how effective they might be in the United Kingdom.
 

Vouchers linked to passing saliva tests

The phase 3 Cessation in Pregnancy Incentives Trial was based on an earlier feasibility study in Glasgow and involved 941 pregnant women aged 16 or older, with a mean age of 27.9 years when they were recruited, from seven stop-smoking services in Scotland, Northern Ireland, and England between January 2018 and April 2020. Participants self-reported that they smoked at least one cigarette a week.

The cohort was randomised into two groups: a control group who received usual stop smoking support that included the offer of counselling by trained workers combined with free nicotine-replacement therapy, and an intervention group who were given the same interventional support plus targets to receive LoveToShop vouchers.

Although vouchers to the value of £400 were on offer, earning them depended on successfully reaching four milestones. They received a first £50 voucher for engaging with stop-smoking services and setting a quit date and further vouchers for being declared smoke-free by biochemical verification at specific time points in the pregnancy.

Factors including the mother’s age, years of smoking, income, use of nicotine-replacement therapy and e-cigarettes, timing of birth, and birth weight were taken into account.

The study found that 71% of the participants in the incentive group engaged with stop-smoking services and set a quit date, compared with 64% in the control group. By late pregnancy, 126 participants (27%) of the 471 in the intervention group were smoke-free, compared with 58 (12%) of the 470 in the control group.
 

Most women in the trial went back to smoking

However, abstinence rates measured 6 months after giving birth were low in both groups: 6% in the intervention group vs. 4% in the control group.

The researchers also reported no significant differences in birth weight between the two groups.

Overall, the birth weight of babies from 443 intervention participants and 450 controls showed no significant difference between groups (average 3.18 kg vs. 3.13 kg).

The researchers did find a clinically important but not significant 10% increase in birth weight in the subset of participants who adhered with their treatment allocation, but they said further analysis is needed to better understand the relevance of this finding.

Severity of preterm birth was similar between groups, and all serious adverse events, such as miscarriages and stillbirths, were considered unrelated to the intervention.

The researchers acknowledged some limitations to their investigation, including that only 23% of women screened by stop-smoking services were enrolled, and that almost all participants were White. Also, the onset of COVID-19 disrupted some of the trial processes.

However, they concluded that their trial “supports implementation advocated in NICE [National Institute for Health and Care Excellence] guidelines by showing an effective, cost-effective, and generalisable pragmatic bolt-on U.K. format for incentive payments” to reduce smoking rates in pregnancy.

A version of this article first appeared on MedscapeUK.

Offering shopping vouchers to pregnant women as an incentive to quit smoking showed promising results, a study found, despite most participants relapsing after giving birth.

Rewarding pregnant women with up to £400 to spend on Main Street, in addition to usual support, more than doubled the proportion who were still smoke-free late in their pregnancy, and could save the National Health Service money in the long term, according to the research, published in the BMJ, led by the University of Glasgow and the University of York, England.

Although the proportion of women in the United Kingdom who smoke during pregnancy has halved over the past 20 years, those who still do are more reluctant to engage with cessation services.

Interventions using financial incentives were pioneered in the United States, but there is a lack of evidence for how effective they might be in the United Kingdom.
 

Vouchers linked to passing saliva tests

The phase 3 Cessation in Pregnancy Incentives Trial was based on an earlier feasibility study in Glasgow and involved 941 pregnant women aged 16 or older, with a mean age of 27.9 years when they were recruited, from seven stop-smoking services in Scotland, Northern Ireland, and England between January 2018 and April 2020. Participants self-reported that they smoked at least one cigarette a week.

The cohort was randomised into two groups: a control group who received usual stop smoking support that included the offer of counselling by trained workers combined with free nicotine-replacement therapy, and an intervention group who were given the same interventional support plus targets to receive LoveToShop vouchers.

Although vouchers to the value of £400 were on offer, earning them depended on successfully reaching four milestones. They received a first £50 voucher for engaging with stop-smoking services and setting a quit date and further vouchers for being declared smoke-free by biochemical verification at specific time points in the pregnancy.

Factors including the mother’s age, years of smoking, income, use of nicotine-replacement therapy and e-cigarettes, timing of birth, and birth weight were taken into account.

The study found that 71% of the participants in the incentive group engaged with stop-smoking services and set a quit date, compared with 64% in the control group. By late pregnancy, 126 participants (27%) of the 471 in the intervention group were smoke-free, compared with 58 (12%) of the 470 in the control group.
 

Most women in the trial went back to smoking

However, abstinence rates measured 6 months after giving birth were low in both groups: 6% in the intervention group vs. 4% in the control group.

The researchers also reported no significant differences in birth weight between the two groups.

Overall, the birth weight of babies from 443 intervention participants and 450 controls showed no significant difference between groups (average 3.18 kg vs. 3.13 kg).

The researchers did find a clinically important but not significant 10% increase in birth weight in the subset of participants who adhered with their treatment allocation, but they said further analysis is needed to better understand the relevance of this finding.

Severity of preterm birth was similar between groups, and all serious adverse events, such as miscarriages and stillbirths, were considered unrelated to the intervention.

The researchers acknowledged some limitations to their investigation, including that only 23% of women screened by stop-smoking services were enrolled, and that almost all participants were White. Also, the onset of COVID-19 disrupted some of the trial processes.

However, they concluded that their trial “supports implementation advocated in NICE [National Institute for Health and Care Excellence] guidelines by showing an effective, cost-effective, and generalisable pragmatic bolt-on U.K. format for incentive payments” to reduce smoking rates in pregnancy.

A version of this article first appeared on MedscapeUK.

Offering shopping vouchers to pregnant women as an incentive to quit smoking showed promising results, a study found, despite most participants relapsing after giving birth.

Rewarding pregnant women with up to £400 to spend on Main Street, in addition to usual support, more than doubled the proportion who were still smoke-free late in their pregnancy, and could save the National Health Service money in the long term, according to the research, published in the BMJ, led by the University of Glasgow and the University of York, England.

Although the proportion of women in the United Kingdom who smoke during pregnancy has halved over the past 20 years, those who still do are more reluctant to engage with cessation services.

Interventions using financial incentives were pioneered in the United States, but there is a lack of evidence for how effective they might be in the United Kingdom.
 

Vouchers linked to passing saliva tests

The phase 3 Cessation in Pregnancy Incentives Trial was based on an earlier feasibility study in Glasgow and involved 941 pregnant women aged 16 or older, with a mean age of 27.9 years when they were recruited, from seven stop-smoking services in Scotland, Northern Ireland, and England between January 2018 and April 2020. Participants self-reported that they smoked at least one cigarette a week.

The cohort was randomised into two groups: a control group who received usual stop smoking support that included the offer of counselling by trained workers combined with free nicotine-replacement therapy, and an intervention group who were given the same interventional support plus targets to receive LoveToShop vouchers.

Although vouchers to the value of £400 were on offer, earning them depended on successfully reaching four milestones. They received a first £50 voucher for engaging with stop-smoking services and setting a quit date and further vouchers for being declared smoke-free by biochemical verification at specific time points in the pregnancy.

Factors including the mother’s age, years of smoking, income, use of nicotine-replacement therapy and e-cigarettes, timing of birth, and birth weight were taken into account.

The study found that 71% of the participants in the incentive group engaged with stop-smoking services and set a quit date, compared with 64% in the control group. By late pregnancy, 126 participants (27%) of the 471 in the intervention group were smoke-free, compared with 58 (12%) of the 470 in the control group.
 

Most women in the trial went back to smoking

However, abstinence rates measured 6 months after giving birth were low in both groups: 6% in the intervention group vs. 4% in the control group.

The researchers also reported no significant differences in birth weight between the two groups.

Overall, the birth weight of babies from 443 intervention participants and 450 controls showed no significant difference between groups (average 3.18 kg vs. 3.13 kg).

The researchers did find a clinically important but not significant 10% increase in birth weight in the subset of participants who adhered with their treatment allocation, but they said further analysis is needed to better understand the relevance of this finding.

Severity of preterm birth was similar between groups, and all serious adverse events, such as miscarriages and stillbirths, were considered unrelated to the intervention.

The researchers acknowledged some limitations to their investigation, including that only 23% of women screened by stop-smoking services were enrolled, and that almost all participants were White. Also, the onset of COVID-19 disrupted some of the trial processes.

However, they concluded that their trial “supports implementation advocated in NICE [National Institute for Health and Care Excellence] guidelines by showing an effective, cost-effective, and generalisable pragmatic bolt-on U.K. format for incentive payments” to reduce smoking rates in pregnancy.

A version of this article first appeared on MedscapeUK.

Each year, the AGA Research Foundation provides research funding to transform the lives of talented investigators.

What will the practice of gastroenterology look like in 20 years? It is our hope that physicians have an abundance of new tools and treatments to care for their patients suffering from digestive disorders.

How will we get there? New treatments and devices are the result of years of research.

To help make this dream a reality, AGA – through the AGA Research Foundation – has made a commitment to support investigators in GI and hepatology with its Research Awards Program. In the past year, the AGA Research Foundation provided $2.5 million in research funding to 61 highly qualified investigators. These diverse researchers range from young investigators to more seasoned leaders in GI, all embarking on novel research projects that will advance our understanding of digestive conditions and pave the way for future discoveries in the field.

The AGA Research Foundation sincerely thanks all of its donors – without their contributions, this work wouldn’t be possible.

You can help spark the scientific breakthroughs of today so clinicians will have the tools to improve care tomorrow. Donate your tax-deductible gift today at www.gastro.org/donateonline.

Each year, the AGA Research Foundation provides research funding to transform the lives of talented investigators.

What will the practice of gastroenterology look like in 20 years? It is our hope that physicians have an abundance of new tools and treatments to care for their patients suffering from digestive disorders.

How will we get there? New treatments and devices are the result of years of research.

To help make this dream a reality, AGA – through the AGA Research Foundation – has made a commitment to support investigators in GI and hepatology with its Research Awards Program. In the past year, the AGA Research Foundation provided $2.5 million in research funding to 61 highly qualified investigators. These diverse researchers range from young investigators to more seasoned leaders in GI, all embarking on novel research projects that will advance our understanding of digestive conditions and pave the way for future discoveries in the field.

The AGA Research Foundation sincerely thanks all of its donors – without their contributions, this work wouldn’t be possible.

You can help spark the scientific breakthroughs of today so clinicians will have the tools to improve care tomorrow. Donate your tax-deductible gift today at www.gastro.org/donateonline.

Each year, the AGA Research Foundation provides research funding to transform the lives of talented investigators.

What will the practice of gastroenterology look like in 20 years? It is our hope that physicians have an abundance of new tools and treatments to care for their patients suffering from digestive disorders.

How will we get there? New treatments and devices are the result of years of research.

To help make this dream a reality, AGA – through the AGA Research Foundation – has made a commitment to support investigators in GI and hepatology with its Research Awards Program. In the past year, the AGA Research Foundation provided $2.5 million in research funding to 61 highly qualified investigators. These diverse researchers range from young investigators to more seasoned leaders in GI, all embarking on novel research projects that will advance our understanding of digestive conditions and pave the way for future discoveries in the field.

The AGA Research Foundation sincerely thanks all of its donors – without their contributions, this work wouldn’t be possible.

You can help spark the scientific breakthroughs of today so clinicians will have the tools to improve care tomorrow. Donate your tax-deductible gift today at www.gastro.org/donateonline.

The Intersociety Group on Diversity, in partnership with researchers at the University of California, Los Angeles, released results of the first study of its kind to explore perspectives on workforce diversity and health equity among practicing GI and hepatology professionals.

The report — Diversity, Equity, and Inclusion in GI and Hepatology: A Survey of Where We Stand — was published jointly in Gastroenterology, Gastrointestinal Endoscopy, HEPATOLOGY, and The American Journal of Gastroenterology. An executive summary is also available in the Journal of Pediatric Gastroenterology and Nutrition.
 

Key findings:

1. Many are complacent with current levels of diversity. Despite the well-recognized under-representation of certain racial and ethnic groups in GI/hepatology, a small proportion of survey participants (one-third or fewer) felt that racial/ethnic representation was insufficient in the educational/training pipeline, among practicing professionals, or in GI/hepatology leadership. There was a clear discrepancy in satisfaction with workplace diversity among GI and hepatology physicians by race and ethnicity: Overall, 63% of Black physicians were very or somewhat unsatisfied with workplace diversity, whereas 78% of White physicians were very or somewhat satisfied.

2. Interventions are needed. Among those who recommended interventions to enhance racial and gender diversity in the profession, the most common suggestions were to increase the following:

• Mentorship opportunities for resident and medical students who are women or from racial and ethnic populations underrepresented in medicine relative to their numbers in the general population. These groups have traditionally included Latino (i.e., Latino/a/x), Black/African American, Native American individuals (namely, American Indians, Alaska Natives, and Native Hawaiians), Pacific Islanders, and mainland Puerto Ricans.
• Representation of underrepresented in medicine GI/hepatology professionals in academic and professional society leadership.

More than 1,200 individuals participated in this nationwide, cross-sectional, 33-question survey. The survey was developed by University of California, Los Angeles investigators Folasade P. May, MD, PhD, MPhil; Harman Rahal, MD; James H. Tabibian, MD, PhD; and Liu Yang, PhD. The IGD, co-chaired at the time by Darrell M. Gray, II, MD, MPH, and Rachel Issaka, MD, MAS, provided input and facilitated survey distribution.


 

The Intersociety Group on Diversity, in partnership with researchers at the University of California, Los Angeles, released results of the first study of its kind to explore perspectives on workforce diversity and health equity among practicing GI and hepatology professionals.

The report — Diversity, Equity, and Inclusion in GI and Hepatology: A Survey of Where We Stand — was published jointly in Gastroenterology, Gastrointestinal Endoscopy, HEPATOLOGY, and The American Journal of Gastroenterology. An executive summary is also available in the Journal of Pediatric Gastroenterology and Nutrition.
 

Key findings:

1. Many are complacent with current levels of diversity. Despite the well-recognized under-representation of certain racial and ethnic groups in GI/hepatology, a small proportion of survey participants (one-third or fewer) felt that racial/ethnic representation was insufficient in the educational/training pipeline, among practicing professionals, or in GI/hepatology leadership. There was a clear discrepancy in satisfaction with workplace diversity among GI and hepatology physicians by race and ethnicity: Overall, 63% of Black physicians were very or somewhat unsatisfied with workplace diversity, whereas 78% of White physicians were very or somewhat satisfied.

2. Interventions are needed. Among those who recommended interventions to enhance racial and gender diversity in the profession, the most common suggestions were to increase the following:

• Mentorship opportunities for resident and medical students who are women or from racial and ethnic populations underrepresented in medicine relative to their numbers in the general population. These groups have traditionally included Latino (i.e., Latino/a/x), Black/African American, Native American individuals (namely, American Indians, Alaska Natives, and Native Hawaiians), Pacific Islanders, and mainland Puerto Ricans.
• Representation of underrepresented in medicine GI/hepatology professionals in academic and professional society leadership.

More than 1,200 individuals participated in this nationwide, cross-sectional, 33-question survey. The survey was developed by University of California, Los Angeles investigators Folasade P. May, MD, PhD, MPhil; Harman Rahal, MD; James H. Tabibian, MD, PhD; and Liu Yang, PhD. The IGD, co-chaired at the time by Darrell M. Gray, II, MD, MPH, and Rachel Issaka, MD, MAS, provided input and facilitated survey distribution.


 

The Intersociety Group on Diversity, in partnership with researchers at the University of California, Los Angeles, released results of the first study of its kind to explore perspectives on workforce diversity and health equity among practicing GI and hepatology professionals.

The report — Diversity, Equity, and Inclusion in GI and Hepatology: A Survey of Where We Stand — was published jointly in Gastroenterology, Gastrointestinal Endoscopy, HEPATOLOGY, and The American Journal of Gastroenterology. An executive summary is also available in the Journal of Pediatric Gastroenterology and Nutrition.
 

Key findings:

1. Many are complacent with current levels of diversity. Despite the well-recognized under-representation of certain racial and ethnic groups in GI/hepatology, a small proportion of survey participants (one-third or fewer) felt that racial/ethnic representation was insufficient in the educational/training pipeline, among practicing professionals, or in GI/hepatology leadership. There was a clear discrepancy in satisfaction with workplace diversity among GI and hepatology physicians by race and ethnicity: Overall, 63% of Black physicians were very or somewhat unsatisfied with workplace diversity, whereas 78% of White physicians were very or somewhat satisfied.

2. Interventions are needed. Among those who recommended interventions to enhance racial and gender diversity in the profession, the most common suggestions were to increase the following:

• Mentorship opportunities for resident and medical students who are women or from racial and ethnic populations underrepresented in medicine relative to their numbers in the general population. These groups have traditionally included Latino (i.e., Latino/a/x), Black/African American, Native American individuals (namely, American Indians, Alaska Natives, and Native Hawaiians), Pacific Islanders, and mainland Puerto Ricans.
• Representation of underrepresented in medicine GI/hepatology professionals in academic and professional society leadership.

More than 1,200 individuals participated in this nationwide, cross-sectional, 33-question survey. The survey was developed by University of California, Los Angeles investigators Folasade P. May, MD, PhD, MPhil; Harman Rahal, MD; James H. Tabibian, MD, PhD; and Liu Yang, PhD. The IGD, co-chaired at the time by Darrell M. Gray, II, MD, MPH, and Rachel Issaka, MD, MAS, provided input and facilitated survey distribution.


 

There has been significant progress in recent years in the treatment of head and neck cancer, and there are useful evidence-based guidelines to inform treatment choices. But less guidance is available when it comes to follow-up and surveillance of patients who have gone into remission.

Existing guidelines for advanced head and neck cancer follow-up are quite broad, with recommended follow-ups ranging from 11 to 27 visits in the 5 years following treatment and no consideration of subtypes.

“Once patients complete treatment for head and neck cancer in particular, they move into survivorship and surveillance phases, and then we are sort of just following patients based on expert opinion,” said Daniel Clayburgh, MD, PhD.

A new study, published online in JAMA Otolaryngology–Head & Neck Surgery, used a novel approach to group head and neck cancer subtypes and calculate optimal follow-up schedules for each.

“They found that in the low-risk types of cancers like HPV-related oropharynx cancers, you really don’t need to see patients all that often because they tend to do quite well, versus the patients that don’t do very well in the long run, such as hypopharyngeal cancers. Their model predicts that you need to see them much, much more often. When you compare that to our guidelines, it says that we’re probably seeing some patients too often, and then there are other patients who we may not be seeing often enough,” said Dr. Clayburgh, who was asked to comment on the study. He is an associate professor of otolaryngology head and neck surgery at Oregon Health and Science University, Portland, and chief of surgery at the Portland VA Healthcare System.

“I thought it was a clever approach to investigate this other aspect of cancer care that often is a little bit overlooked,” said Dr. Clayburgh. who coauthored an invited commentary published in conjunction with the study.

He said the study results are intriguing, but not quite ready for general clinical practice. The study did not include oral cavity cancers, which are a major subtype, and the results need to be validated in larger patient populations. He also pointed out that recurrence is only one reason to see patients after the treatment phase. “There are long term treatment effects. There are various mental health issues and other health issues that they can have aside from just cancer. So it can be helpful to see patients more often than just purely as dictated on how often they’re going to have a cancer recurrence. I don’t think we’re quite there to exactly what is the right number of visits or how often they need to come in, but I think (this paper is) an important step toward that, and it definitely provides fodder for modification of current guidelines,” Dr. Clayburgh said.
 

The study details

The researchers estimated event-free survival, defined as the time from end of treatment to any event, using a piecewise exponential model. Optimal follow-up timepoint was defined through the occurrence of a 5% event rate. The study included 673 patients with locally advanced head and neck cancer, with a median age of 58 years. A total of 82.5% were men. The researchers did not report race or ethnicity. Over a median follow-up of 57.8 months, frequency of events was 18.9% among 227 patients with nasopharyngeal cancer (NPC), 14.8% among 237 patients with human papillomavirus-positive oropharyngeal cancer (HPV+ OPC), 36.2% among 47 patients with HPV– OPC, 44.6% among 65 patients with hypopharyngeal cancer (HPC), and 30.9% among 97 patients with laryngeal cancer (LC).

The researchers divided follow-up into a period of response evaluation and close follow-up, which included the first 6 months after end of treatment, and three phases: 6.0 to 16.5 months (first phase); 16.5 to 25.0 months (second phase); and 25.0 to 99.0 months (third phase). Open follow-up continues after the third phase.

The researchers identified surveillance intervals for each phase for the five patient groups: NPC, HPV+ OPC, HPV– OPC, HPC, and LC. They identified substantially different follow-up intervals for each. The longest intervals were recommended for HPV+ OPC and NPC patients, and the shortest for HPC. Overall, there was a threefold difference in the number of follow-ups recommended among HNC groups.

“Given the limited health care resources and the rising number of patients with head and neck cancer, patient-tailored and evidence-based assessment schedules will benefit both patients and health systems. Further investigation for consensus guidelines is needed, and we hope that the findings of this study will aid in their establishment in the near future,” the authors wrote.

The study is limited by its reliance on retrospective data, and must be validated in other patient populations before it is suitable for clinical practice.

Dr. Clayburgh has no relevant financial disclosures.

There has been significant progress in recent years in the treatment of head and neck cancer, and there are useful evidence-based guidelines to inform treatment choices. But less guidance is available when it comes to follow-up and surveillance of patients who have gone into remission.

Existing guidelines for advanced head and neck cancer follow-up are quite broad, with recommended follow-ups ranging from 11 to 27 visits in the 5 years following treatment and no consideration of subtypes.

“Once patients complete treatment for head and neck cancer in particular, they move into survivorship and surveillance phases, and then we are sort of just following patients based on expert opinion,” said Daniel Clayburgh, MD, PhD.

A new study, published online in JAMA Otolaryngology–Head & Neck Surgery, used a novel approach to group head and neck cancer subtypes and calculate optimal follow-up schedules for each.

“They found that in the low-risk types of cancers like HPV-related oropharynx cancers, you really don’t need to see patients all that often because they tend to do quite well, versus the patients that don’t do very well in the long run, such as hypopharyngeal cancers. Their model predicts that you need to see them much, much more often. When you compare that to our guidelines, it says that we’re probably seeing some patients too often, and then there are other patients who we may not be seeing often enough,” said Dr. Clayburgh, who was asked to comment on the study. He is an associate professor of otolaryngology head and neck surgery at Oregon Health and Science University, Portland, and chief of surgery at the Portland VA Healthcare System.

“I thought it was a clever approach to investigate this other aspect of cancer care that often is a little bit overlooked,” said Dr. Clayburgh. who coauthored an invited commentary published in conjunction with the study.

He said the study results are intriguing, but not quite ready for general clinical practice. The study did not include oral cavity cancers, which are a major subtype, and the results need to be validated in larger patient populations. He also pointed out that recurrence is only one reason to see patients after the treatment phase. “There are long term treatment effects. There are various mental health issues and other health issues that they can have aside from just cancer. So it can be helpful to see patients more often than just purely as dictated on how often they’re going to have a cancer recurrence. I don’t think we’re quite there to exactly what is the right number of visits or how often they need to come in, but I think (this paper is) an important step toward that, and it definitely provides fodder for modification of current guidelines,” Dr. Clayburgh said.
 

The study details

The researchers estimated event-free survival, defined as the time from end of treatment to any event, using a piecewise exponential model. Optimal follow-up timepoint was defined through the occurrence of a 5% event rate. The study included 673 patients with locally advanced head and neck cancer, with a median age of 58 years. A total of 82.5% were men. The researchers did not report race or ethnicity. Over a median follow-up of 57.8 months, frequency of events was 18.9% among 227 patients with nasopharyngeal cancer (NPC), 14.8% among 237 patients with human papillomavirus-positive oropharyngeal cancer (HPV+ OPC), 36.2% among 47 patients with HPV– OPC, 44.6% among 65 patients with hypopharyngeal cancer (HPC), and 30.9% among 97 patients with laryngeal cancer (LC).

The researchers divided follow-up into a period of response evaluation and close follow-up, which included the first 6 months after end of treatment, and three phases: 6.0 to 16.5 months (first phase); 16.5 to 25.0 months (second phase); and 25.0 to 99.0 months (third phase). Open follow-up continues after the third phase.

The researchers identified surveillance intervals for each phase for the five patient groups: NPC, HPV+ OPC, HPV– OPC, HPC, and LC. They identified substantially different follow-up intervals for each. The longest intervals were recommended for HPV+ OPC and NPC patients, and the shortest for HPC. Overall, there was a threefold difference in the number of follow-ups recommended among HNC groups.

“Given the limited health care resources and the rising number of patients with head and neck cancer, patient-tailored and evidence-based assessment schedules will benefit both patients and health systems. Further investigation for consensus guidelines is needed, and we hope that the findings of this study will aid in their establishment in the near future,” the authors wrote.

The study is limited by its reliance on retrospective data, and must be validated in other patient populations before it is suitable for clinical practice.

Dr. Clayburgh has no relevant financial disclosures.

There has been significant progress in recent years in the treatment of head and neck cancer, and there are useful evidence-based guidelines to inform treatment choices. But less guidance is available when it comes to follow-up and surveillance of patients who have gone into remission.

Existing guidelines for advanced head and neck cancer follow-up are quite broad, with recommended follow-ups ranging from 11 to 27 visits in the 5 years following treatment and no consideration of subtypes.

“Once patients complete treatment for head and neck cancer in particular, they move into survivorship and surveillance phases, and then we are sort of just following patients based on expert opinion,” said Daniel Clayburgh, MD, PhD.

A new study, published online in JAMA Otolaryngology–Head & Neck Surgery, used a novel approach to group head and neck cancer subtypes and calculate optimal follow-up schedules for each.

“They found that in the low-risk types of cancers like HPV-related oropharynx cancers, you really don’t need to see patients all that often because they tend to do quite well, versus the patients that don’t do very well in the long run, such as hypopharyngeal cancers. Their model predicts that you need to see them much, much more often. When you compare that to our guidelines, it says that we’re probably seeing some patients too often, and then there are other patients who we may not be seeing often enough,” said Dr. Clayburgh, who was asked to comment on the study. He is an associate professor of otolaryngology head and neck surgery at Oregon Health and Science University, Portland, and chief of surgery at the Portland VA Healthcare System.

“I thought it was a clever approach to investigate this other aspect of cancer care that often is a little bit overlooked,” said Dr. Clayburgh. who coauthored an invited commentary published in conjunction with the study.

He said the study results are intriguing, but not quite ready for general clinical practice. The study did not include oral cavity cancers, which are a major subtype, and the results need to be validated in larger patient populations. He also pointed out that recurrence is only one reason to see patients after the treatment phase. “There are long term treatment effects. There are various mental health issues and other health issues that they can have aside from just cancer. So it can be helpful to see patients more often than just purely as dictated on how often they’re going to have a cancer recurrence. I don’t think we’re quite there to exactly what is the right number of visits or how often they need to come in, but I think (this paper is) an important step toward that, and it definitely provides fodder for modification of current guidelines,” Dr. Clayburgh said.
 

The study details

The researchers estimated event-free survival, defined as the time from end of treatment to any event, using a piecewise exponential model. Optimal follow-up timepoint was defined through the occurrence of a 5% event rate. The study included 673 patients with locally advanced head and neck cancer, with a median age of 58 years. A total of 82.5% were men. The researchers did not report race or ethnicity. Over a median follow-up of 57.8 months, frequency of events was 18.9% among 227 patients with nasopharyngeal cancer (NPC), 14.8% among 237 patients with human papillomavirus-positive oropharyngeal cancer (HPV+ OPC), 36.2% among 47 patients with HPV– OPC, 44.6% among 65 patients with hypopharyngeal cancer (HPC), and 30.9% among 97 patients with laryngeal cancer (LC).

The researchers divided follow-up into a period of response evaluation and close follow-up, which included the first 6 months after end of treatment, and three phases: 6.0 to 16.5 months (first phase); 16.5 to 25.0 months (second phase); and 25.0 to 99.0 months (third phase). Open follow-up continues after the third phase.

The researchers identified surveillance intervals for each phase for the five patient groups: NPC, HPV+ OPC, HPV– OPC, HPC, and LC. They identified substantially different follow-up intervals for each. The longest intervals were recommended for HPV+ OPC and NPC patients, and the shortest for HPC. Overall, there was a threefold difference in the number of follow-ups recommended among HNC groups.

“Given the limited health care resources and the rising number of patients with head and neck cancer, patient-tailored and evidence-based assessment schedules will benefit both patients and health systems. Further investigation for consensus guidelines is needed, and we hope that the findings of this study will aid in their establishment in the near future,” the authors wrote.

The study is limited by its reliance on retrospective data, and must be validated in other patient populations before it is suitable for clinical practice.

Dr. Clayburgh has no relevant financial disclosures.

An optimistic new review offers guidance about treating mantle cell lymphoma (MCL) in the new era of chimeric antigen receptor (CAR)-T cell therapy and medication choices informed by risk stratification.

Traditionally, MCL has had a notoriously poor prognosis and is still impossible to cure. But survival rates are rising thanks to better treatments, the review authors wrote, and even relapsed/refractory patients have a growing number of options that can potentially give them extra years of life.

“Prognosis has certainly changed in past 10 years. We have been able to have an excellent control of disease, and patients are living longer, even past the 8- or 10-year mark,” Moffit Cancer Center/Memorial Healthcare System hematologist-oncologist Jose Sandoval‐Sus, MD, said in an interview. He is corresponding author of the review, which appeared in the October issue of Current Oncology Reports.

MCL – which affects cells in the mantle zone of lymph nodes – is rare. It usually strikes older men, often presents at an advanced stage, and accounts for 6%-8% of non-Hodgkin lymphomas in the United States.

Prognoses are improving. The review highlights a study released earlier this year that found that median 5-year overall survival has increased from 68.8% (2002-2009) to 81.6% (2010-2015).

Now, the review notes, there are several first-line chemotherapy options that combine agents with rituximab such as rituximab/bendamustine, which “has generally been established as an effective treatment for MCL at first relapse in patients who are bendamustine naive when compared to other chemotherapy agents.”

Other treatments include rituximab, bortezomib, cyclophosphamide, doxorubicin, vincristine, and prednisolone; rituximab, bendamustine and cytarabine; and rituximab, gemcitabine, and oxaliplatin.

“I think of rituximab as a medication of maintenance, either after autologous stem cell transplant or even in patients who have not been through transplant,” Dr. Sandoval‐Sus said. “As maintenance, it really has improved outcomes for these patients.”

But the first step before treatment, he said, is to explore prognostic factors such as alterations on the TP53 gene that “really dictate a lot in terms of the prognosis of patients.” As the review notes, these alterations – either bi-allelic del17p or TP53 mutations – “are associated with poor outcomes after frontline and salvage regimens, including targeted agents such as Burton’s tyrosine kinase inhibitors (BTKis).”

These patients, who make up about 20% of those with MCL, also are most unlikely to benefit from autologous stem cell transplantation, Dr. Sandoval‐Sus said.

What about refracted/relapsed (R/R) cases? BTKis have been a major advance for these patients, he said. However, choosing the best drug can be a challenge. As the review notes, “all approved BTKis for R/R MCL seem to have similar clinical outcomes based on identical mechanism of action, and there are no prospective trials comparing these agents in a head-to-head fashion.”

The authors added that “we wonder if AEs [adverse events] could be decreased by using combinations based on new generation BTKi, but it is still a question that needs to be resolved in the clinical trial arena.”

Stem cell transplants may be an option, the review said, but “in practice the clinical benefit ... is limited to single-center series or small multi-institutional registries with few prospective studies.”

Then there’s CAR-T cell therapy, the game-changer. A type called brexucabtagene autoleucel (Brexu-cel) is now approved in MCL, the review authors wrote, and real-world data “serve as a platform to expand CAR-T therapy to more R/R MCL patients that do not fit the strict inclusion criteria of the studies (e.g., controlled comorbidities and worse performance status)... We strongly recommend early referral of these patients to accredited institutions with ample cellular therapy experience, including high-risk MCL patients (e.g., blastoid/pleomorphic morphology, biallelic del17p, TP53 mutations) so an appropriate bridging strategy and a CAR-T cell roadmap is planned with the patient and caretakers.”

Some researchers are exploring combination treatment with both BTKis and CAR T-cell therapy, “which may be considered for patients with R/R MCL who are naive to both CAR T-cell and BTKi therapy, because combination therapy may increase treatment efficacy,” wrote the authors of another review that appeared in the October issue of Current Oncology Reports. “Based on limited data in patients with CLL, BTKi therapy may be initiated as bridging therapy and continued during lymphodepletion prior to CAR T-cell infusion”

What’s next? Multiple treatments are in the research stage, Dr. Sandoval‐Sus said. “There are a lot of things in development that are really incredible.”

Reversible BTKis, for example, appear to be effective at controlling disease and are well-tolerated, he said. “And we are awaiting the results of clinical trials of targeted therapies.”

For now, he said, the best advice for hematologists is to gain a full understanding of a patient’s MCL, in order to provide the most appropriate treatment. Community oncologists should get at least one second opinion from an academic center or other clinic that treats these kinds of lymphomas, he said, and molecular tests are crucial. A discussion about stem cell transplantation after remission is a good idea, he said, and so is an exploration of clinical trials “from the get-go.”

“In patients who relapse and have high-risk features, they should be started on a BTKi inhibitor for the most part,” he said, “although we need to weigh risks and benefits between the side effects of different BTKi inhibitors. And they should be referred earlier to a CAR T cell therapy center, so they can discuss the benefits and see if they’re an appropriate patient. I think patients are being referred a little bit too late in the second- or third-line setting.”

What about CAR T therapy as a first-line therapy? It’s not FDA-approved, Dr. Sandoval‐Sus said, and “definitely not a standard of care.” But clinical trials are exploring the idea, he said. As for messages to patients, Dr. Sandoval-Sus said he would tell them that MCL is not yet curable, “but the future is very bright.”

Dr. Sandoval-Sus declared advisory board relationships with Seagen, Incyte, Janssen, ADC Therapeutics, TG therapeutics, and Genmab. The other review authors had no disclosures.

An optimistic new review offers guidance about treating mantle cell lymphoma (MCL) in the new era of chimeric antigen receptor (CAR)-T cell therapy and medication choices informed by risk stratification.

Traditionally, MCL has had a notoriously poor prognosis and is still impossible to cure. But survival rates are rising thanks to better treatments, the review authors wrote, and even relapsed/refractory patients have a growing number of options that can potentially give them extra years of life.

“Prognosis has certainly changed in past 10 years. We have been able to have an excellent control of disease, and patients are living longer, even past the 8- or 10-year mark,” Moffit Cancer Center/Memorial Healthcare System hematologist-oncologist Jose Sandoval‐Sus, MD, said in an interview. He is corresponding author of the review, which appeared in the October issue of Current Oncology Reports.

MCL – which affects cells in the mantle zone of lymph nodes – is rare. It usually strikes older men, often presents at an advanced stage, and accounts for 6%-8% of non-Hodgkin lymphomas in the United States.

Prognoses are improving. The review highlights a study released earlier this year that found that median 5-year overall survival has increased from 68.8% (2002-2009) to 81.6% (2010-2015).

Now, the review notes, there are several first-line chemotherapy options that combine agents with rituximab such as rituximab/bendamustine, which “has generally been established as an effective treatment for MCL at first relapse in patients who are bendamustine naive when compared to other chemotherapy agents.”

Other treatments include rituximab, bortezomib, cyclophosphamide, doxorubicin, vincristine, and prednisolone; rituximab, bendamustine and cytarabine; and rituximab, gemcitabine, and oxaliplatin.

“I think of rituximab as a medication of maintenance, either after autologous stem cell transplant or even in patients who have not been through transplant,” Dr. Sandoval‐Sus said. “As maintenance, it really has improved outcomes for these patients.”

But the first step before treatment, he said, is to explore prognostic factors such as alterations on the TP53 gene that “really dictate a lot in terms of the prognosis of patients.” As the review notes, these alterations – either bi-allelic del17p or TP53 mutations – “are associated with poor outcomes after frontline and salvage regimens, including targeted agents such as Burton’s tyrosine kinase inhibitors (BTKis).”

These patients, who make up about 20% of those with MCL, also are most unlikely to benefit from autologous stem cell transplantation, Dr. Sandoval‐Sus said.

What about refracted/relapsed (R/R) cases? BTKis have been a major advance for these patients, he said. However, choosing the best drug can be a challenge. As the review notes, “all approved BTKis for R/R MCL seem to have similar clinical outcomes based on identical mechanism of action, and there are no prospective trials comparing these agents in a head-to-head fashion.”

The authors added that “we wonder if AEs [adverse events] could be decreased by using combinations based on new generation BTKi, but it is still a question that needs to be resolved in the clinical trial arena.”

Stem cell transplants may be an option, the review said, but “in practice the clinical benefit ... is limited to single-center series or small multi-institutional registries with few prospective studies.”

Then there’s CAR-T cell therapy, the game-changer. A type called brexucabtagene autoleucel (Brexu-cel) is now approved in MCL, the review authors wrote, and real-world data “serve as a platform to expand CAR-T therapy to more R/R MCL patients that do not fit the strict inclusion criteria of the studies (e.g., controlled comorbidities and worse performance status)... We strongly recommend early referral of these patients to accredited institutions with ample cellular therapy experience, including high-risk MCL patients (e.g., blastoid/pleomorphic morphology, biallelic del17p, TP53 mutations) so an appropriate bridging strategy and a CAR-T cell roadmap is planned with the patient and caretakers.”

Some researchers are exploring combination treatment with both BTKis and CAR T-cell therapy, “which may be considered for patients with R/R MCL who are naive to both CAR T-cell and BTKi therapy, because combination therapy may increase treatment efficacy,” wrote the authors of another review that appeared in the October issue of Current Oncology Reports. “Based on limited data in patients with CLL, BTKi therapy may be initiated as bridging therapy and continued during lymphodepletion prior to CAR T-cell infusion”

What’s next? Multiple treatments are in the research stage, Dr. Sandoval‐Sus said. “There are a lot of things in development that are really incredible.”

Reversible BTKis, for example, appear to be effective at controlling disease and are well-tolerated, he said. “And we are awaiting the results of clinical trials of targeted therapies.”

For now, he said, the best advice for hematologists is to gain a full understanding of a patient’s MCL, in order to provide the most appropriate treatment. Community oncologists should get at least one second opinion from an academic center or other clinic that treats these kinds of lymphomas, he said, and molecular tests are crucial. A discussion about stem cell transplantation after remission is a good idea, he said, and so is an exploration of clinical trials “from the get-go.”

“In patients who relapse and have high-risk features, they should be started on a BTKi inhibitor for the most part,” he said, “although we need to weigh risks and benefits between the side effects of different BTKi inhibitors. And they should be referred earlier to a CAR T cell therapy center, so they can discuss the benefits and see if they’re an appropriate patient. I think patients are being referred a little bit too late in the second- or third-line setting.”

What about CAR T therapy as a first-line therapy? It’s not FDA-approved, Dr. Sandoval‐Sus said, and “definitely not a standard of care.” But clinical trials are exploring the idea, he said. As for messages to patients, Dr. Sandoval-Sus said he would tell them that MCL is not yet curable, “but the future is very bright.”

Dr. Sandoval-Sus declared advisory board relationships with Seagen, Incyte, Janssen, ADC Therapeutics, TG therapeutics, and Genmab. The other review authors had no disclosures.

An optimistic new review offers guidance about treating mantle cell lymphoma (MCL) in the new era of chimeric antigen receptor (CAR)-T cell therapy and medication choices informed by risk stratification.

Traditionally, MCL has had a notoriously poor prognosis and is still impossible to cure. But survival rates are rising thanks to better treatments, the review authors wrote, and even relapsed/refractory patients have a growing number of options that can potentially give them extra years of life.

“Prognosis has certainly changed in past 10 years. We have been able to have an excellent control of disease, and patients are living longer, even past the 8- or 10-year mark,” Moffit Cancer Center/Memorial Healthcare System hematologist-oncologist Jose Sandoval‐Sus, MD, said in an interview. He is corresponding author of the review, which appeared in the October issue of Current Oncology Reports.

MCL – which affects cells in the mantle zone of lymph nodes – is rare. It usually strikes older men, often presents at an advanced stage, and accounts for 6%-8% of non-Hodgkin lymphomas in the United States.

Prognoses are improving. The review highlights a study released earlier this year that found that median 5-year overall survival has increased from 68.8% (2002-2009) to 81.6% (2010-2015).

Now, the review notes, there are several first-line chemotherapy options that combine agents with rituximab such as rituximab/bendamustine, which “has generally been established as an effective treatment for MCL at first relapse in patients who are bendamustine naive when compared to other chemotherapy agents.”

Other treatments include rituximab, bortezomib, cyclophosphamide, doxorubicin, vincristine, and prednisolone; rituximab, bendamustine and cytarabine; and rituximab, gemcitabine, and oxaliplatin.

“I think of rituximab as a medication of maintenance, either after autologous stem cell transplant or even in patients who have not been through transplant,” Dr. Sandoval‐Sus said. “As maintenance, it really has improved outcomes for these patients.”

But the first step before treatment, he said, is to explore prognostic factors such as alterations on the TP53 gene that “really dictate a lot in terms of the prognosis of patients.” As the review notes, these alterations – either bi-allelic del17p or TP53 mutations – “are associated with poor outcomes after frontline and salvage regimens, including targeted agents such as Burton’s tyrosine kinase inhibitors (BTKis).”

These patients, who make up about 20% of those with MCL, also are most unlikely to benefit from autologous stem cell transplantation, Dr. Sandoval‐Sus said.

What about refracted/relapsed (R/R) cases? BTKis have been a major advance for these patients, he said. However, choosing the best drug can be a challenge. As the review notes, “all approved BTKis for R/R MCL seem to have similar clinical outcomes based on identical mechanism of action, and there are no prospective trials comparing these agents in a head-to-head fashion.”

The authors added that “we wonder if AEs [adverse events] could be decreased by using combinations based on new generation BTKi, but it is still a question that needs to be resolved in the clinical trial arena.”

Stem cell transplants may be an option, the review said, but “in practice the clinical benefit ... is limited to single-center series or small multi-institutional registries with few prospective studies.”

Then there’s CAR-T cell therapy, the game-changer. A type called brexucabtagene autoleucel (Brexu-cel) is now approved in MCL, the review authors wrote, and real-world data “serve as a platform to expand CAR-T therapy to more R/R MCL patients that do not fit the strict inclusion criteria of the studies (e.g., controlled comorbidities and worse performance status)... We strongly recommend early referral of these patients to accredited institutions with ample cellular therapy experience, including high-risk MCL patients (e.g., blastoid/pleomorphic morphology, biallelic del17p, TP53 mutations) so an appropriate bridging strategy and a CAR-T cell roadmap is planned with the patient and caretakers.”

Some researchers are exploring combination treatment with both BTKis and CAR T-cell therapy, “which may be considered for patients with R/R MCL who are naive to both CAR T-cell and BTKi therapy, because combination therapy may increase treatment efficacy,” wrote the authors of another review that appeared in the October issue of Current Oncology Reports. “Based on limited data in patients with CLL, BTKi therapy may be initiated as bridging therapy and continued during lymphodepletion prior to CAR T-cell infusion”

What’s next? Multiple treatments are in the research stage, Dr. Sandoval‐Sus said. “There are a lot of things in development that are really incredible.”

Reversible BTKis, for example, appear to be effective at controlling disease and are well-tolerated, he said. “And we are awaiting the results of clinical trials of targeted therapies.”

For now, he said, the best advice for hematologists is to gain a full understanding of a patient’s MCL, in order to provide the most appropriate treatment. Community oncologists should get at least one second opinion from an academic center or other clinic that treats these kinds of lymphomas, he said, and molecular tests are crucial. A discussion about stem cell transplantation after remission is a good idea, he said, and so is an exploration of clinical trials “from the get-go.”

“In patients who relapse and have high-risk features, they should be started on a BTKi inhibitor for the most part,” he said, “although we need to weigh risks and benefits between the side effects of different BTKi inhibitors. And they should be referred earlier to a CAR T cell therapy center, so they can discuss the benefits and see if they’re an appropriate patient. I think patients are being referred a little bit too late in the second- or third-line setting.”

What about CAR T therapy as a first-line therapy? It’s not FDA-approved, Dr. Sandoval‐Sus said, and “definitely not a standard of care.” But clinical trials are exploring the idea, he said. As for messages to patients, Dr. Sandoval-Sus said he would tell them that MCL is not yet curable, “but the future is very bright.”

Dr. Sandoval-Sus declared advisory board relationships with Seagen, Incyte, Janssen, ADC Therapeutics, TG therapeutics, and Genmab. The other review authors had no disclosures.

A pregnant patient who had COVID-19 showed up at a hospital with respiratory difficulty caused by her illness. Physicians had to perform an emergency delivery of her near-term baby.

The infant survived, but the woman lost oxygen during the ordeal and suffered hypoxic brain damage. She is now suing an obstetrician, a pulmonologist, and an intensive care unit physician for medical malpractice.

The plaintiff contends there was a failure “to adequately recognize and treat her condition,” said Peter Kolbert, senior vice president for claim and litigation services for Healthcare Risk Advisors, part of TDC Group, which includes national medical liability insurer The Doctors Company.

“The physicians involved vehemently disagree and believe they treated her appropriately,” Mr. Kolbert said. “In fact, we believe their actions were heroic.”

In another case, a patient with COVID-19 and multiple comorbidities was admitted to a hospital. Physicians sedated and intubated the patient to maintain her airway. She recovered, but the patient now alleges doctors were negligent because she developed ulcers during her hospital stay. The case occurred during the height of the pandemic. In addition to the hospital, a pulmonologist, an ICU physician, and an acute care physician are named in the suit.

Both of these lawsuits are being defined as COVID claims because at the time, the plaintiffs either had COVID and needed care because of COVID, or because the care that physicians provided was affected by COVID in some way.

In the second case, the patient had COVID and needed treatment. During her recovery, ulcers developed. A significant aspect of this case is that it occurred during the height of the pandemic. Hospitals were overcrowded, the staff was swamped, and resources were limited. One factor may be that physicians were doing the best they could at the time but that the pandemic affected the extent of care they could provide.

Physicians have long worried about the legal consequences of COVID-19 and whether lawsuits might arise from the care that was provided or that was delayed by the pandemic. Now, new data reflect the grim news: COVID claims have arrived. These cases from the claims database of The Doctors Company are just two examples of many COVID-related claims that have been levied since the pandemic started.

Currently, there are 162 open COVID-related claims in The Doctors Company database, according to Mr. Kolbert. A September 2022 benchmark report from Aon and the American Society for Health Care Risk Management indicates that 245 claims that pertain to patients with confirmed or suspected COVID-19 have been filed since the pandemic began. The findings in this report stem from an analysis of 95,600 hospital and physician liability claims that occurred between 2012 and 2021.

Of the 245 cases, 89 claims have been closed. The average cost was $43,000 per claim, said Kanika Vats, a director and actuary for Aon, a global firm that provides risk, reinsurance, and health solutions. Six of the claims cost $300,000 or more; the highest settlement was for $700,000.

“Most of the allegations in these claims revolve around delay in treatment or delay in diagnosis,” Ms. Vats said.
 

Which specialties are involved in legal actions?

Physicians working in acute care settings such as emergency departments and urgent care centers are the primary targets in COVID-related lawsuits involving doctors, say legal analysts. However, other specialties are also being affected. Physicians being sued include some who practiced telemedicine during the pandemic.

In one case, a primary care physician saw a patient via telemedicine because the physical medical office was closed. The patient was evaluated virtually and was sent for bloodwork and an x-ray.

The patient is now suing the primary care physician, alleging that failure to immediately send her to a hospital resulted in tuberculosis going untreated and that the failure led to a bad outcome. The allegation is that the physician underevaluated the case during the telemedicine visit, Mr. Kolbert said.

Drew Graham, an attorney at Hall Booth Smith PC, which is based in New York, said that most of the COVID-related liability claims he has seen involve facilities that provide postacute care, such as nursing homes and assisted living facilities. His firm has also seen a small number of COVID-related claims against physicians.

At least two of the claims involved allegations of improper treatment of COVID during hospitalizations, he said. Another involved a telehealth visit in which the patient claimed the virtual care that was provided was improper and that their condition required an in-person examination. Mr. Graham declined to specify the specialties of the physicians sued.

The Medical Professional Liability Association reports similar trends in COVID-related claims. Long-term facilities and hospitals are the most common focus of COVID-19 claims, followed by emergency medicine, primary care, and ob/gyn medical specialties, according to Kwon Miller, manager of data and analytics for MPL Association, a national trade association for medical liability insurers that operates a large claims database.

Between January 2020 and June 2022, the MPL Association Data Sharing Project recorded 280 COVID-19 events. “Events” refers to notifications, licensing board inquiries, and claims involving COVID. Of these events, 180 were closed with no indemnity payment, and 13 were closed with an average indemnity payment of $3,816, Mr. Miller said.

Complaints of delayed care associated with the pandemic are also on the rise. For example, one patient is suing a gastroenterologist for delaying his colonoscopy, alleging the postponement led to a delayed colon cancer diagnosis and worse prognosis, Mr. Kolbert said.

“It was delayed because all elective procedures at the time were being put off,” he said. “The patient claims that had they received the scheduled screening, the cancer would have been diagnosed at stage I as opposed to stage III.”
 

Why isn’t federal immunity shielding physicians?

A pressing question about the growing number of COVID claims is why state and federal immunity isn’t preventing such lawsuits.

In 2020, the U.S. Department of Health & Human Services published a declaration under the Public Readiness and Emergency Preparedness Act (PREP Act) that provided liability immunity to health care professionals for any activity related to medical countermeasures against COVID-19. The act allows an exception for negligence claims associated with death or serious injury caused by willful misconduct.

At the same time, most states implemented laws or executive orders shielding physicians from liability claims related to the prevention and treatment of COVID-19, unless gross negligence or willful misconduct is proven.

Mr. Graham said some COVID-related claims against physicians have included allegations of gross negligence to avoid the application of state immunity, while others combine allegations of deviations from standard of care unrelated to the pandemic.

Some plaintiffs are attempting to skirt the protections by making complaints sound as if they’re not related to COVID-19, Mr. Kolbert said. That way, they don’t have to prove gross negligence or willful misconduct at all.

“The filings at first blush may not tell you it’s a COVID case, but it may be a COVID case,” he said. “Plaintiffs’ attorneys are trying to assert that COVID defenses do not apply and that these cases are ‘traditional physician negligence’ claims. They’re trying to plead around the protections.”

The federal and state immunities are likely keeping the volume of COVID claims down overall and are discouraging some complaints from moving forward, attorneys say.

But because some plaintiffs are downplaying or ignoring the COVID association, it’s likely that more COVID lawsuits exist than anyone realizes, according to Mr. Kolbert.

“I expect there’s an underestimation of how many COVID claims are really out there,” he said.
 

What does the future hold for COVID claims?

Currently, the frequency and the severity of COVID claims are low, Ms. Vats said. She believes the cost of such claims will continue to remain at low levels.

“But again, there is a lot of uncertainty,” she said. “This year, states have started to roll back their immunity protections, and in a lot of states, there is no cap in awarding [noneconomic] damages. There could well be a scenario where they allege wrongful death, and in a state with no cap on the pain and suffering component, if juries continue to behave the way they have been behaving, we could see aberration verdicts.”

Another lingering issue concerns which court systems have jurisdiction in cases involving COVID-related claims. Because of the nationwide response to the pandemic, Mr. Graham thinks it makes sense that federal courts handle the cases, but the plaintiffs’ bar has generally been opposed to federal jurisdiction.

“A second issue is the long-term impact of COVID litigation on our providers,” he said. “If the protections in place to limit liability are determined to be ineffective, our state and federal leaders must act aggressively and in a bipartisan way to make sure our health care providers are protected when we face the next crisis.”

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

A pregnant patient who had COVID-19 showed up at a hospital with respiratory difficulty caused by her illness. Physicians had to perform an emergency delivery of her near-term baby.

The infant survived, but the woman lost oxygen during the ordeal and suffered hypoxic brain damage. She is now suing an obstetrician, a pulmonologist, and an intensive care unit physician for medical malpractice.

The plaintiff contends there was a failure “to adequately recognize and treat her condition,” said Peter Kolbert, senior vice president for claim and litigation services for Healthcare Risk Advisors, part of TDC Group, which includes national medical liability insurer The Doctors Company.

“The physicians involved vehemently disagree and believe they treated her appropriately,” Mr. Kolbert said. “In fact, we believe their actions were heroic.”

In another case, a patient with COVID-19 and multiple comorbidities was admitted to a hospital. Physicians sedated and intubated the patient to maintain her airway. She recovered, but the patient now alleges doctors were negligent because she developed ulcers during her hospital stay. The case occurred during the height of the pandemic. In addition to the hospital, a pulmonologist, an ICU physician, and an acute care physician are named in the suit.

Both of these lawsuits are being defined as COVID claims because at the time, the plaintiffs either had COVID and needed care because of COVID, or because the care that physicians provided was affected by COVID in some way.

In the second case, the patient had COVID and needed treatment. During her recovery, ulcers developed. A significant aspect of this case is that it occurred during the height of the pandemic. Hospitals were overcrowded, the staff was swamped, and resources were limited. One factor may be that physicians were doing the best they could at the time but that the pandemic affected the extent of care they could provide.

Physicians have long worried about the legal consequences of COVID-19 and whether lawsuits might arise from the care that was provided or that was delayed by the pandemic. Now, new data reflect the grim news: COVID claims have arrived. These cases from the claims database of The Doctors Company are just two examples of many COVID-related claims that have been levied since the pandemic started.

Currently, there are 162 open COVID-related claims in The Doctors Company database, according to Mr. Kolbert. A September 2022 benchmark report from Aon and the American Society for Health Care Risk Management indicates that 245 claims that pertain to patients with confirmed or suspected COVID-19 have been filed since the pandemic began. The findings in this report stem from an analysis of 95,600 hospital and physician liability claims that occurred between 2012 and 2021.

Of the 245 cases, 89 claims have been closed. The average cost was $43,000 per claim, said Kanika Vats, a director and actuary for Aon, a global firm that provides risk, reinsurance, and health solutions. Six of the claims cost $300,000 or more; the highest settlement was for $700,000.

“Most of the allegations in these claims revolve around delay in treatment or delay in diagnosis,” Ms. Vats said.
 

Which specialties are involved in legal actions?

Physicians working in acute care settings such as emergency departments and urgent care centers are the primary targets in COVID-related lawsuits involving doctors, say legal analysts. However, other specialties are also being affected. Physicians being sued include some who practiced telemedicine during the pandemic.

In one case, a primary care physician saw a patient via telemedicine because the physical medical office was closed. The patient was evaluated virtually and was sent for bloodwork and an x-ray.

The patient is now suing the primary care physician, alleging that failure to immediately send her to a hospital resulted in tuberculosis going untreated and that the failure led to a bad outcome. The allegation is that the physician underevaluated the case during the telemedicine visit, Mr. Kolbert said.

Drew Graham, an attorney at Hall Booth Smith PC, which is based in New York, said that most of the COVID-related liability claims he has seen involve facilities that provide postacute care, such as nursing homes and assisted living facilities. His firm has also seen a small number of COVID-related claims against physicians.

At least two of the claims involved allegations of improper treatment of COVID during hospitalizations, he said. Another involved a telehealth visit in which the patient claimed the virtual care that was provided was improper and that their condition required an in-person examination. Mr. Graham declined to specify the specialties of the physicians sued.

The Medical Professional Liability Association reports similar trends in COVID-related claims. Long-term facilities and hospitals are the most common focus of COVID-19 claims, followed by emergency medicine, primary care, and ob/gyn medical specialties, according to Kwon Miller, manager of data and analytics for MPL Association, a national trade association for medical liability insurers that operates a large claims database.

Between January 2020 and June 2022, the MPL Association Data Sharing Project recorded 280 COVID-19 events. “Events” refers to notifications, licensing board inquiries, and claims involving COVID. Of these events, 180 were closed with no indemnity payment, and 13 were closed with an average indemnity payment of $3,816, Mr. Miller said.

Complaints of delayed care associated with the pandemic are also on the rise. For example, one patient is suing a gastroenterologist for delaying his colonoscopy, alleging the postponement led to a delayed colon cancer diagnosis and worse prognosis, Mr. Kolbert said.

“It was delayed because all elective procedures at the time were being put off,” he said. “The patient claims that had they received the scheduled screening, the cancer would have been diagnosed at stage I as opposed to stage III.”
 

Why isn’t federal immunity shielding physicians?

A pressing question about the growing number of COVID claims is why state and federal immunity isn’t preventing such lawsuits.

In 2020, the U.S. Department of Health & Human Services published a declaration under the Public Readiness and Emergency Preparedness Act (PREP Act) that provided liability immunity to health care professionals for any activity related to medical countermeasures against COVID-19. The act allows an exception for negligence claims associated with death or serious injury caused by willful misconduct.

At the same time, most states implemented laws or executive orders shielding physicians from liability claims related to the prevention and treatment of COVID-19, unless gross negligence or willful misconduct is proven.

Mr. Graham said some COVID-related claims against physicians have included allegations of gross negligence to avoid the application of state immunity, while others combine allegations of deviations from standard of care unrelated to the pandemic.

Some plaintiffs are attempting to skirt the protections by making complaints sound as if they’re not related to COVID-19, Mr. Kolbert said. That way, they don’t have to prove gross negligence or willful misconduct at all.

“The filings at first blush may not tell you it’s a COVID case, but it may be a COVID case,” he said. “Plaintiffs’ attorneys are trying to assert that COVID defenses do not apply and that these cases are ‘traditional physician negligence’ claims. They’re trying to plead around the protections.”

The federal and state immunities are likely keeping the volume of COVID claims down overall and are discouraging some complaints from moving forward, attorneys say.

But because some plaintiffs are downplaying or ignoring the COVID association, it’s likely that more COVID lawsuits exist than anyone realizes, according to Mr. Kolbert.

“I expect there’s an underestimation of how many COVID claims are really out there,” he said.
 

What does the future hold for COVID claims?

Currently, the frequency and the severity of COVID claims are low, Ms. Vats said. She believes the cost of such claims will continue to remain at low levels.

“But again, there is a lot of uncertainty,” she said. “This year, states have started to roll back their immunity protections, and in a lot of states, there is no cap in awarding [noneconomic] damages. There could well be a scenario where they allege wrongful death, and in a state with no cap on the pain and suffering component, if juries continue to behave the way they have been behaving, we could see aberration verdicts.”

Another lingering issue concerns which court systems have jurisdiction in cases involving COVID-related claims. Because of the nationwide response to the pandemic, Mr. Graham thinks it makes sense that federal courts handle the cases, but the plaintiffs’ bar has generally been opposed to federal jurisdiction.

“A second issue is the long-term impact of COVID litigation on our providers,” he said. “If the protections in place to limit liability are determined to be ineffective, our state and federal leaders must act aggressively and in a bipartisan way to make sure our health care providers are protected when we face the next crisis.”

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

A pregnant patient who had COVID-19 showed up at a hospital with respiratory difficulty caused by her illness. Physicians had to perform an emergency delivery of her near-term baby.

The infant survived, but the woman lost oxygen during the ordeal and suffered hypoxic brain damage. She is now suing an obstetrician, a pulmonologist, and an intensive care unit physician for medical malpractice.

The plaintiff contends there was a failure “to adequately recognize and treat her condition,” said Peter Kolbert, senior vice president for claim and litigation services for Healthcare Risk Advisors, part of TDC Group, which includes national medical liability insurer The Doctors Company.

“The physicians involved vehemently disagree and believe they treated her appropriately,” Mr. Kolbert said. “In fact, we believe their actions were heroic.”

In another case, a patient with COVID-19 and multiple comorbidities was admitted to a hospital. Physicians sedated and intubated the patient to maintain her airway. She recovered, but the patient now alleges doctors were negligent because she developed ulcers during her hospital stay. The case occurred during the height of the pandemic. In addition to the hospital, a pulmonologist, an ICU physician, and an acute care physician are named in the suit.

Both of these lawsuits are being defined as COVID claims because at the time, the plaintiffs either had COVID and needed care because of COVID, or because the care that physicians provided was affected by COVID in some way.

In the second case, the patient had COVID and needed treatment. During her recovery, ulcers developed. A significant aspect of this case is that it occurred during the height of the pandemic. Hospitals were overcrowded, the staff was swamped, and resources were limited. One factor may be that physicians were doing the best they could at the time but that the pandemic affected the extent of care they could provide.

Physicians have long worried about the legal consequences of COVID-19 and whether lawsuits might arise from the care that was provided or that was delayed by the pandemic. Now, new data reflect the grim news: COVID claims have arrived. These cases from the claims database of The Doctors Company are just two examples of many COVID-related claims that have been levied since the pandemic started.

Currently, there are 162 open COVID-related claims in The Doctors Company database, according to Mr. Kolbert. A September 2022 benchmark report from Aon and the American Society for Health Care Risk Management indicates that 245 claims that pertain to patients with confirmed or suspected COVID-19 have been filed since the pandemic began. The findings in this report stem from an analysis of 95,600 hospital and physician liability claims that occurred between 2012 and 2021.

Of the 245 cases, 89 claims have been closed. The average cost was $43,000 per claim, said Kanika Vats, a director and actuary for Aon, a global firm that provides risk, reinsurance, and health solutions. Six of the claims cost $300,000 or more; the highest settlement was for $700,000.

“Most of the allegations in these claims revolve around delay in treatment or delay in diagnosis,” Ms. Vats said.
 

Which specialties are involved in legal actions?

Physicians working in acute care settings such as emergency departments and urgent care centers are the primary targets in COVID-related lawsuits involving doctors, say legal analysts. However, other specialties are also being affected. Physicians being sued include some who practiced telemedicine during the pandemic.

In one case, a primary care physician saw a patient via telemedicine because the physical medical office was closed. The patient was evaluated virtually and was sent for bloodwork and an x-ray.

The patient is now suing the primary care physician, alleging that failure to immediately send her to a hospital resulted in tuberculosis going untreated and that the failure led to a bad outcome. The allegation is that the physician underevaluated the case during the telemedicine visit, Mr. Kolbert said.

Drew Graham, an attorney at Hall Booth Smith PC, which is based in New York, said that most of the COVID-related liability claims he has seen involve facilities that provide postacute care, such as nursing homes and assisted living facilities. His firm has also seen a small number of COVID-related claims against physicians.

At least two of the claims involved allegations of improper treatment of COVID during hospitalizations, he said. Another involved a telehealth visit in which the patient claimed the virtual care that was provided was improper and that their condition required an in-person examination. Mr. Graham declined to specify the specialties of the physicians sued.

The Medical Professional Liability Association reports similar trends in COVID-related claims. Long-term facilities and hospitals are the most common focus of COVID-19 claims, followed by emergency medicine, primary care, and ob/gyn medical specialties, according to Kwon Miller, manager of data and analytics for MPL Association, a national trade association for medical liability insurers that operates a large claims database.

Between January 2020 and June 2022, the MPL Association Data Sharing Project recorded 280 COVID-19 events. “Events” refers to notifications, licensing board inquiries, and claims involving COVID. Of these events, 180 were closed with no indemnity payment, and 13 were closed with an average indemnity payment of $3,816, Mr. Miller said.

Complaints of delayed care associated with the pandemic are also on the rise. For example, one patient is suing a gastroenterologist for delaying his colonoscopy, alleging the postponement led to a delayed colon cancer diagnosis and worse prognosis, Mr. Kolbert said.

“It was delayed because all elective procedures at the time were being put off,” he said. “The patient claims that had they received the scheduled screening, the cancer would have been diagnosed at stage I as opposed to stage III.”
 

Why isn’t federal immunity shielding physicians?

A pressing question about the growing number of COVID claims is why state and federal immunity isn’t preventing such lawsuits.

In 2020, the U.S. Department of Health & Human Services published a declaration under the Public Readiness and Emergency Preparedness Act (PREP Act) that provided liability immunity to health care professionals for any activity related to medical countermeasures against COVID-19. The act allows an exception for negligence claims associated with death or serious injury caused by willful misconduct.

At the same time, most states implemented laws or executive orders shielding physicians from liability claims related to the prevention and treatment of COVID-19, unless gross negligence or willful misconduct is proven.

Mr. Graham said some COVID-related claims against physicians have included allegations of gross negligence to avoid the application of state immunity, while others combine allegations of deviations from standard of care unrelated to the pandemic.

Some plaintiffs are attempting to skirt the protections by making complaints sound as if they’re not related to COVID-19, Mr. Kolbert said. That way, they don’t have to prove gross negligence or willful misconduct at all.

“The filings at first blush may not tell you it’s a COVID case, but it may be a COVID case,” he said. “Plaintiffs’ attorneys are trying to assert that COVID defenses do not apply and that these cases are ‘traditional physician negligence’ claims. They’re trying to plead around the protections.”

The federal and state immunities are likely keeping the volume of COVID claims down overall and are discouraging some complaints from moving forward, attorneys say.

But because some plaintiffs are downplaying or ignoring the COVID association, it’s likely that more COVID lawsuits exist than anyone realizes, according to Mr. Kolbert.

“I expect there’s an underestimation of how many COVID claims are really out there,” he said.
 

What does the future hold for COVID claims?

Currently, the frequency and the severity of COVID claims are low, Ms. Vats said. She believes the cost of such claims will continue to remain at low levels.

“But again, there is a lot of uncertainty,” she said. “This year, states have started to roll back their immunity protections, and in a lot of states, there is no cap in awarding [noneconomic] damages. There could well be a scenario where they allege wrongful death, and in a state with no cap on the pain and suffering component, if juries continue to behave the way they have been behaving, we could see aberration verdicts.”

Another lingering issue concerns which court systems have jurisdiction in cases involving COVID-related claims. Because of the nationwide response to the pandemic, Mr. Graham thinks it makes sense that federal courts handle the cases, but the plaintiffs’ bar has generally been opposed to federal jurisdiction.

“A second issue is the long-term impact of COVID litigation on our providers,” he said. “If the protections in place to limit liability are determined to be ineffective, our state and federal leaders must act aggressively and in a bipartisan way to make sure our health care providers are protected when we face the next crisis.”

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

The authors of a new evidence review recommend the Canadian TIA Risk Score for managing patients who present to the emergency department or physician’s office with an apparent transient ischemic attack (TIA) or minor stroke.

“Many hospitals do not have enough stroke neurologists to see every patient with TIA or minor stroke within 24 hours. Likewise, many emergency departments around the world are stretched beyond capacity,” study author Jeffery J. Perry, MD, senior scientist at the Ottawa Hospital Research Institute, said in an interview.

“This review corresponds to most of the recommendations by the American Heart Association and the Canadian Stroke Best Practice Recommendations,” he said. “It does, however, go further to differentiate high-risk versus low-risk patients for subsequent stroke using the Canadian TIA Score and offers practical suggestions for how to provide high-quality care in environments without the capacity to provide immediate vascular imaging, immediate MRI scanning, and immediate stroke specialist assessments.”

Most patients at low risk of a subsequent stroke (that is, patients with < 1% risk for a subsequent stroke at 7 days) can be managed safely as outpatients without causing delays in their departure for vascular imaging or neurology consultation during their initial emergency department visits, Dr. Perry added. “The Canadian TIA Score can be used to determine the urgency for an assessment by a stroke neurologist.”

The study was published  in CMAJ.
 

Score stratifies risk

Dr. Perry, lead author of the Canadian TIA Score validation study, said that the CMAJ editorial board approached him to write the review and to incorporate the new score into the latest recommendations. To include the latest evidence, Dr. Perry and colleagues reviewed the most recent position statements on TIA and minor stroke management and searched the literature for relevant articles. They note that the nomenclature related to TIA and minor stroke is inconsistent, that it’s not necessary to differentiate between the two from a clinical standpoint, and that the term “acute ischemic cerebrovascular syndrome” has been proposed to include both.

Broadly, the team’s recommended strategy for the diagnosis and management of the condition includes the following steps:

• Diagnosis: Sudden loss of motor function and impaired speech are strong indicators; symptoms tend to be negative (for example, loss of vision rather than flashing lights).
• Risk assessment: Use of the Canadian TIA Score to stratify 7-day stroke risk (low risk: < 1%, medium risk: 1%-5%, high risk: > 5%).
• Investigations: Urgent CT within 48 hours; vascular imaging to identify acutely symptomatic carotid stenosis in medium- to high-risk patients, as determined on the basis of the TIA score; ECG to identify atrial fibrillation or flutter and to optimize anticoagulant use; if the index of suspicion is high, echocardiography should be employed to look for cardioembolic sources.
• Management: Dual antiplatelet therapy for 21 days in medium- and high-risk patients; hypertension should be managed; patients should be referred for stroke clinic assessment; aggressive lifestyle changes should be initiated to lower lipid levels.

“I believe that our recommendations should be incorporated with the clinical guidelines,” said Dr. Perry.
 

Caveats and concerns

Commenting on the article, Steven M. Greenberg, MD, PhD, vice chair for faculty development of the department of neurology at Massachusetts General Hospital and a professor of neurology at Harvard Medical School, both in Boston, said, “Although the proposed guidelines are broadly evidence-based and consistent with standard of care, there are several areas where stroke specialists might disagree and suggest alternative strategies.” Dr. Greenberg was not involved in the study.

While some lower-risk features, such as repetitive or stereotyped symptoms or vertigo, can be more suggestive of TIA mimics, he said that “these features need to be scrutinized quite carefully. Critical carotid stenosis, for example, can give rise to brief, repetitive, stereotyped low-flow TIAs that require urgent revascularization.”

Vertigo might be a feature of brainstem or cerebellar TIA or minor stroke, said Dr. Greenberg, especially in the setting of other posterior circulation symptoms. Validated guidelines for differentiating peripheral vertigo and CNS vertigo are available, he noted.

“Another caveat is that the studies demonstrating benefit of brief dual antiplatelet therapy following acute TIA or minor stroke were based on ABCD2 rather than the Canadian TIA score,” he said. “It is therefore important for any score-based recommendations to be applied in the overall context of existing stroke prevention guidelines.”

In addition to the recommendation for urgent vascular imaging of patients whose presentations suggest bona fide TIA or minor stroke, most guidelines also recommend extended cardiac monitoring and transthoracic ECG to identify potential sources of embolism, Dr. Greenberg added. “Users of these guidelines should also be aware of the limited yield of head CT, which is able to detect some old strokes, large acute strokes – presumably not relevant to patients presenting with TIA or minor stroke – and acute intracranial hemorrhages.”

Louis R. Caplan, MD, founder of the Harvard Stroke Registry at Beth Israel Deaconess Medical Center, Boston, and a professor of neurology at Harvard Medical School, also commented on the study.

While the review “is okay for care by nonstroke specialists, ideally, major referral centers could have a TIA or stroke clinic, as is present in much of Western Europe,” he said. This would allow the stroke etiology to be investigated for each patient.

“Many patients can be treated with the regimen outlined by the authors, but some with other conditions, such as atrial cardiopathy, patent foramen ovale, atrial myxoma, thrombus within the cardiac ventricle or atrium, will require anticoagulants,” he noted. “Thrombolysis and mechanical thrombectomy would be considered in some. Each stroke patient is different, and management cannot be homogenized into one remedy. One size does not fit all.”

In an accompanying commentary, Shelagh B. Coutts, MD, and Michael D. Hill, MD, both of the University of Calgary (Alta.), presented their team’s approach to the acute management of patients with likely cerebral ischemia. Such management includes risk assessment and stratification by clinical symptoms, rather than a particular score. They also typically conduct CT angiography. “If the CTA is completely normal (that is, no occlusion, no atherosclerosis or arterial dissection and no other vascular abnormality), we rely on the high negative predictive value of this result and discharge the patient home on antiplatelet treatment with outpatient follow-up, including MRI of the brain (since CT cannot reliably rule out minor ischemia) within the first week,” they write.

The review was conducted without commercial funding. Dr. Perry, Dr. Greenberg, Dr. Caplan, Dr. Coutts, and Dr. Hill have disclosed no relevant financial relationships.

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

The authors of a new evidence review recommend the Canadian TIA Risk Score for managing patients who present to the emergency department or physician’s office with an apparent transient ischemic attack (TIA) or minor stroke.

“Many hospitals do not have enough stroke neurologists to see every patient with TIA or minor stroke within 24 hours. Likewise, many emergency departments around the world are stretched beyond capacity,” study author Jeffery J. Perry, MD, senior scientist at the Ottawa Hospital Research Institute, said in an interview.

“This review corresponds to most of the recommendations by the American Heart Association and the Canadian Stroke Best Practice Recommendations,” he said. “It does, however, go further to differentiate high-risk versus low-risk patients for subsequent stroke using the Canadian TIA Score and offers practical suggestions for how to provide high-quality care in environments without the capacity to provide immediate vascular imaging, immediate MRI scanning, and immediate stroke specialist assessments.”

Most patients at low risk of a subsequent stroke (that is, patients with < 1% risk for a subsequent stroke at 7 days) can be managed safely as outpatients without causing delays in their departure for vascular imaging or neurology consultation during their initial emergency department visits, Dr. Perry added. “The Canadian TIA Score can be used to determine the urgency for an assessment by a stroke neurologist.”

The study was published  in CMAJ.
 

Score stratifies risk

Dr. Perry, lead author of the Canadian TIA Score validation study, said that the CMAJ editorial board approached him to write the review and to incorporate the new score into the latest recommendations. To include the latest evidence, Dr. Perry and colleagues reviewed the most recent position statements on TIA and minor stroke management and searched the literature for relevant articles. They note that the nomenclature related to TIA and minor stroke is inconsistent, that it’s not necessary to differentiate between the two from a clinical standpoint, and that the term “acute ischemic cerebrovascular syndrome” has been proposed to include both.

Broadly, the team’s recommended strategy for the diagnosis and management of the condition includes the following steps:

• Diagnosis: Sudden loss of motor function and impaired speech are strong indicators; symptoms tend to be negative (for example, loss of vision rather than flashing lights).
• Risk assessment: Use of the Canadian TIA Score to stratify 7-day stroke risk (low risk: < 1%, medium risk: 1%-5%, high risk: > 5%).
• Investigations: Urgent CT within 48 hours; vascular imaging to identify acutely symptomatic carotid stenosis in medium- to high-risk patients, as determined on the basis of the TIA score; ECG to identify atrial fibrillation or flutter and to optimize anticoagulant use; if the index of suspicion is high, echocardiography should be employed to look for cardioembolic sources.
• Management: Dual antiplatelet therapy for 21 days in medium- and high-risk patients; hypertension should be managed; patients should be referred for stroke clinic assessment; aggressive lifestyle changes should be initiated to lower lipid levels.

“I believe that our recommendations should be incorporated with the clinical guidelines,” said Dr. Perry.
 

Caveats and concerns

Commenting on the article, Steven M. Greenberg, MD, PhD, vice chair for faculty development of the department of neurology at Massachusetts General Hospital and a professor of neurology at Harvard Medical School, both in Boston, said, “Although the proposed guidelines are broadly evidence-based and consistent with standard of care, there are several areas where stroke specialists might disagree and suggest alternative strategies.” Dr. Greenberg was not involved in the study.

While some lower-risk features, such as repetitive or stereotyped symptoms or vertigo, can be more suggestive of TIA mimics, he said that “these features need to be scrutinized quite carefully. Critical carotid stenosis, for example, can give rise to brief, repetitive, stereotyped low-flow TIAs that require urgent revascularization.”

Vertigo might be a feature of brainstem or cerebellar TIA or minor stroke, said Dr. Greenberg, especially in the setting of other posterior circulation symptoms. Validated guidelines for differentiating peripheral vertigo and CNS vertigo are available, he noted.

“Another caveat is that the studies demonstrating benefit of brief dual antiplatelet therapy following acute TIA or minor stroke were based on ABCD2 rather than the Canadian TIA score,” he said. “It is therefore important for any score-based recommendations to be applied in the overall context of existing stroke prevention guidelines.”

In addition to the recommendation for urgent vascular imaging of patients whose presentations suggest bona fide TIA or minor stroke, most guidelines also recommend extended cardiac monitoring and transthoracic ECG to identify potential sources of embolism, Dr. Greenberg added. “Users of these guidelines should also be aware of the limited yield of head CT, which is able to detect some old strokes, large acute strokes – presumably not relevant to patients presenting with TIA or minor stroke – and acute intracranial hemorrhages.”

Louis R. Caplan, MD, founder of the Harvard Stroke Registry at Beth Israel Deaconess Medical Center, Boston, and a professor of neurology at Harvard Medical School, also commented on the study.

While the review “is okay for care by nonstroke specialists, ideally, major referral centers could have a TIA or stroke clinic, as is present in much of Western Europe,” he said. This would allow the stroke etiology to be investigated for each patient.

“Many patients can be treated with the regimen outlined by the authors, but some with other conditions, such as atrial cardiopathy, patent foramen ovale, atrial myxoma, thrombus within the cardiac ventricle or atrium, will require anticoagulants,” he noted. “Thrombolysis and mechanical thrombectomy would be considered in some. Each stroke patient is different, and management cannot be homogenized into one remedy. One size does not fit all.”

In an accompanying commentary, Shelagh B. Coutts, MD, and Michael D. Hill, MD, both of the University of Calgary (Alta.), presented their team’s approach to the acute management of patients with likely cerebral ischemia. Such management includes risk assessment and stratification by clinical symptoms, rather than a particular score. They also typically conduct CT angiography. “If the CTA is completely normal (that is, no occlusion, no atherosclerosis or arterial dissection and no other vascular abnormality), we rely on the high negative predictive value of this result and discharge the patient home on antiplatelet treatment with outpatient follow-up, including MRI of the brain (since CT cannot reliably rule out minor ischemia) within the first week,” they write.

The review was conducted without commercial funding. Dr. Perry, Dr. Greenberg, Dr. Caplan, Dr. Coutts, and Dr. Hill have disclosed no relevant financial relationships.

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

The authors of a new evidence review recommend the Canadian TIA Risk Score for managing patients who present to the emergency department or physician’s office with an apparent transient ischemic attack (TIA) or minor stroke.

“Many hospitals do not have enough stroke neurologists to see every patient with TIA or minor stroke within 24 hours. Likewise, many emergency departments around the world are stretched beyond capacity,” study author Jeffery J. Perry, MD, senior scientist at the Ottawa Hospital Research Institute, said in an interview.

“This review corresponds to most of the recommendations by the American Heart Association and the Canadian Stroke Best Practice Recommendations,” he said. “It does, however, go further to differentiate high-risk versus low-risk patients for subsequent stroke using the Canadian TIA Score and offers practical suggestions for how to provide high-quality care in environments without the capacity to provide immediate vascular imaging, immediate MRI scanning, and immediate stroke specialist assessments.”

Most patients at low risk of a subsequent stroke (that is, patients with < 1% risk for a subsequent stroke at 7 days) can be managed safely as outpatients without causing delays in their departure for vascular imaging or neurology consultation during their initial emergency department visits, Dr. Perry added. “The Canadian TIA Score can be used to determine the urgency for an assessment by a stroke neurologist.”

The study was published  in CMAJ.
 

Score stratifies risk

Dr. Perry, lead author of the Canadian TIA Score validation study, said that the CMAJ editorial board approached him to write the review and to incorporate the new score into the latest recommendations. To include the latest evidence, Dr. Perry and colleagues reviewed the most recent position statements on TIA and minor stroke management and searched the literature for relevant articles. They note that the nomenclature related to TIA and minor stroke is inconsistent, that it’s not necessary to differentiate between the two from a clinical standpoint, and that the term “acute ischemic cerebrovascular syndrome” has been proposed to include both.

Broadly, the team’s recommended strategy for the diagnosis and management of the condition includes the following steps:

• Diagnosis: Sudden loss of motor function and impaired speech are strong indicators; symptoms tend to be negative (for example, loss of vision rather than flashing lights).
• Risk assessment: Use of the Canadian TIA Score to stratify 7-day stroke risk (low risk: < 1%, medium risk: 1%-5%, high risk: > 5%).
• Investigations: Urgent CT within 48 hours; vascular imaging to identify acutely symptomatic carotid stenosis in medium- to high-risk patients, as determined on the basis of the TIA score; ECG to identify atrial fibrillation or flutter and to optimize anticoagulant use; if the index of suspicion is high, echocardiography should be employed to look for cardioembolic sources.
• Management: Dual antiplatelet therapy for 21 days in medium- and high-risk patients; hypertension should be managed; patients should be referred for stroke clinic assessment; aggressive lifestyle changes should be initiated to lower lipid levels.

“I believe that our recommendations should be incorporated with the clinical guidelines,” said Dr. Perry.
 

Caveats and concerns

Commenting on the article, Steven M. Greenberg, MD, PhD, vice chair for faculty development of the department of neurology at Massachusetts General Hospital and a professor of neurology at Harvard Medical School, both in Boston, said, “Although the proposed guidelines are broadly evidence-based and consistent with standard of care, there are several areas where stroke specialists might disagree and suggest alternative strategies.” Dr. Greenberg was not involved in the study.

While some lower-risk features, such as repetitive or stereotyped symptoms or vertigo, can be more suggestive of TIA mimics, he said that “these features need to be scrutinized quite carefully. Critical carotid stenosis, for example, can give rise to brief, repetitive, stereotyped low-flow TIAs that require urgent revascularization.”

Vertigo might be a feature of brainstem or cerebellar TIA or minor stroke, said Dr. Greenberg, especially in the setting of other posterior circulation symptoms. Validated guidelines for differentiating peripheral vertigo and CNS vertigo are available, he noted.

“Another caveat is that the studies demonstrating benefit of brief dual antiplatelet therapy following acute TIA or minor stroke were based on ABCD2 rather than the Canadian TIA score,” he said. “It is therefore important for any score-based recommendations to be applied in the overall context of existing stroke prevention guidelines.”

In addition to the recommendation for urgent vascular imaging of patients whose presentations suggest bona fide TIA or minor stroke, most guidelines also recommend extended cardiac monitoring and transthoracic ECG to identify potential sources of embolism, Dr. Greenberg added. “Users of these guidelines should also be aware of the limited yield of head CT, which is able to detect some old strokes, large acute strokes – presumably not relevant to patients presenting with TIA or minor stroke – and acute intracranial hemorrhages.”

Louis R. Caplan, MD, founder of the Harvard Stroke Registry at Beth Israel Deaconess Medical Center, Boston, and a professor of neurology at Harvard Medical School, also commented on the study.

While the review “is okay for care by nonstroke specialists, ideally, major referral centers could have a TIA or stroke clinic, as is present in much of Western Europe,” he said. This would allow the stroke etiology to be investigated for each patient.

“Many patients can be treated with the regimen outlined by the authors, but some with other conditions, such as atrial cardiopathy, patent foramen ovale, atrial myxoma, thrombus within the cardiac ventricle or atrium, will require anticoagulants,” he noted. “Thrombolysis and mechanical thrombectomy would be considered in some. Each stroke patient is different, and management cannot be homogenized into one remedy. One size does not fit all.”

In an accompanying commentary, Shelagh B. Coutts, MD, and Michael D. Hill, MD, both of the University of Calgary (Alta.), presented their team’s approach to the acute management of patients with likely cerebral ischemia. Such management includes risk assessment and stratification by clinical symptoms, rather than a particular score. They also typically conduct CT angiography. “If the CTA is completely normal (that is, no occlusion, no atherosclerosis or arterial dissection and no other vascular abnormality), we rely on the high negative predictive value of this result and discharge the patient home on antiplatelet treatment with outpatient follow-up, including MRI of the brain (since CT cannot reliably rule out minor ischemia) within the first week,” they write.

The review was conducted without commercial funding. Dr. Perry, Dr. Greenberg, Dr. Caplan, Dr. Coutts, and Dr. Hill have disclosed no relevant financial relationships.

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

VIENNA – The investigational agent xanomeline-trospium (KarXT, Karuna Therapeutics) achieves significant and clinically meaningful improvements in schizophrenia symptom scores without causing problematic adverse effects, new research suggests.

Results from the phase 3 EMERGENT-2 trial, which included more than 250 patients with schizophrenia, showed that those who received xanomeline-trospium for 5 weeks achieved a significant reduction in Positive and Negative Syndrome Scale (PANSS) total scores of more than nine points compared with their peers who received placebo. In addition, the improvements started at week 2.

Alongside significant reductions in both positive and negative symptoms, the results suggest the agent was well tolerated, with treatment-emergent adverse events (TEAEs) largely mild to moderate and transient in nature.

Lead investigator Christoph U. Correll, MD, professor of psychiatry at the Zucker School of Medicine at Hofstra/Northwell, Uniondale, New York, told this news organization that the upcoming EMERGENT-3 study will have a “European component” and that the “readout is expected most likely in the first quarter of next year.”

Dr. Correll suggested that if leads to “two positive studies and reasonable safety,” the novel agent may become part of the “next generation of antipsychotics that are not related to postsynaptic dopamine blockade.”

The findings for EMERGENT-2, presented at the 35th European College of Neuropsychopharmacology (ECNP) Congress as a poster and as an oral presentation, were an update of topline results released earlier this year.
 

Novel compound

Xanomeline-trospium is a novel compound that combines the dual M1/M4-preferring muscarinic receptor agonist effect of xanomeline with the peripherally restricted muscarinic receptor antagonist effect of trospium.

A previous phase 2 trial that compared the drug with placebo in almost 200 patients suggested it significantly reduced psychosis symptoms, leading to the current phase 3 trial.

Dr. Correll noted that xanomeline-trospium reduces psychosis via a “bottom up and top down approach.”

He said that on one hand, M4 agonism decreases acetylcholine in the ventral tegmental area and the associated stratum, “which then decreases dopamine levels from the bottom up,” while the M1 agonism stimulates GABA and decreases dopamine from the “top down.”

M1 agonism, however, also stimulates the cholinergic system peripherally, “which can give you nausea, vomiting, and also some blood pressure and pulse” problems, Dr. Correll said.

That was the limitation when this approach was studied by Lilly as a treatment for patients with Alzheimer’s disease, but the addition of trospium means “you’re buffering somewhat the cholinergic peripheral effects,” he said.

While that can conversely lead to dyspepsia, dry mouth, and constipation, Dr. Correll noted that the adverse effects of the novel agent are “mitigated by titration,” with patients taking up to 8 days to reach the full dose.

The result is that the drug was “overall tolerated, and the effect sizes were quite astounding,” he reported.
 

Intermittent, time limited TEAEs

The current trial included 252 patients aged 18-65 years (mean age, 45 years) who were confirmed to have schizophrenia and who had recently experienced a worsening of psychotic symptoms that warranted hospitalization. Three-quarters of the participants were men, and a similar proportion were Black. Approximately one quarter were White.

All were randomly assigned in a 1:1 ratio to receive either xanomeline-trospium or placebo following a 2-week screening period.

Xanomeline and trospium were titrated from 50 mg/20 mg twice daily to 125 mg/30 mg twice daily, and patients were treated for a total of 5 weeks. Efficacy and safety analyses were conducted in those who had received at least one dose of the study drug.

At the end of the treatment period, xanomeline-trospium was associated with a significant 9.6-point reduction in PANSS total scores relative to placebo; scores fell by 21.2 points with the active treatment, vs. 11.6 points with placebo (P < .0001).

The significant improvement in PANSS total score began at week 2 (P < .05) and continued to accrue over the course of the study.

Xanomeline-trospium was also associated with significant reductions in PANSS positive subscale scores in comparison with placebo (P < .0001), as well as with reductions in PANSS negative subscale scores (P < .01) and PANSS Marder negative subscale scores (P < .01).

Although 75.4% of patients who received xanomeline-trospium experienced a TEAE, in comparison with 58.4% of the placebo group, very few experienced a serious TEAE (just 1.6% in both groups).

TEAEs leading to discontinuation occurred in 7.1% of the active-treatment group, vs. 5.6% of the placebo group. The overall discontinuation rates from the trial were 25% and 21%, respectively.

The most common TEAEs with xanomeline-trospium were constipation (21.4%), dyspepsia (19.0%), nausea (19.0%), vomiting (14.3%), and headache (13.5%).

The results showed that cholinergic TEAEs typically began within the first 2 weeks of treatment and were “intermittent and time limited in nature,” the investigators noted. Moreover, average blood pressure levels were “similar” between the xanomeline-trospium and placebo groups “at each time point throughout the trial,” they added.

Dr. Correll reported that whereas the EMERGENT studies are testing xanomeline-trospium as a monotherapy, the ARISE program will be examining it as an “augmentation” treatment. “And that’s relevant because, let’s face it, patients do not switch” treatments, he said.

He suggested that if xanomeline-trospium is able to have a synergistic effect with other drugs, “we might be able to treat people who are currently not benefiting enough from postsynaptic dopamine blockade to maybe get a little bit closer” to the benefits seen with clozapine, which “also has problematic side effects.”
 

‘Really revolutionary’

Following the oral presentation of the study by coauthor Stephen K. Brannan, MD, chief medical officer, Karuna Therapeutics, Boston, the results were warmly received.

Session cochair Mark Weiser, MD, chairman at the department of psychiatry, Sackler School of Medicine, Tel Aviv University, Israel, said the agent is “really revolutionary in the field.

“It’s a non-dopamine compound which helps for schizophrenia, so we’re all very optimistic about it,” Dr. Weiser added.

Nevertheless, he asked Dr. Brannan whether the occurrence of gastrointestinal adverse effects with xanomeline-trospium led to “functional unblinding of the study.”

Dr. Brannan answered that the investigators were “really worried about this prior to EMERGENT-1” but that formal testing suggested it was not a problem.

Dr. Brannan said that although this has not yet been formally tested for the current trial, he believes that it is “highly unlikely” that functional unblinding occurred, inasmuch as the “percentages are about in the same range as we saw in EMERGENT-1.”

Speaking to ECNP Congress Daily in a conference roundup video, session cochair Andreas Reif, MD, PhD, professor of psychiatry, psychosomatic medicine, and psychotherapy at the University Hospital of Frankfurt (Germany), also highlighted the study.

He said that along with a study of dexmedetomidine sublingual film for agitation associated with schizophrenia or bipolar disorder that was also presented in the session, the current trial is “pivotal.”

Dr. Reif noted that the effect size shown with xanomeline-trospium was “really amazing.”

“We are in a really exciting time in treating mental disorders,” he said. “Industry is finally investing again, and really has new compounds that will make it to the market.”

Karuna plans to submit a new drug application with the Food and Drug Administration for KarXT in mid-2023. The drug is also in development for the treatment of psychiatric and neurologic conditions other than schizophrenia, including Alzheimer’s disease.

The study was funded by Karuna Therapeutics. Dr. Correll has reported relationships with Karuna, as well as AbbVie, Acadia, Alkermes, Allergan, Angelini, Aristo, Axsome, Boehringer-Ingelheim, Cardio Diagnostics, Cerevel, CNX Therapeutics, Compass Pathways, Damitsa, Gedeon Richter, Hikma, Holmusk, IntraCellular Therapies, Janssen/J&J, LB Pharma, Lundbeck, MedAvante-ProPhase, MedInCell, Medscape, Merck, Mindpax, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Newron, Noven, Otsuka, Pfizer, Pharmabrain, PPD Biotech, Recordati, Relmada, Reviva, Rovi, Seqirus, Servier, SK Life Science, Sumitomo Dainippon, Sunovion, Sun Pharma, Supernus, Takeda, Teva, Viatris, Otsuka, and UpToDate.

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

VIENNA – The investigational agent xanomeline-trospium (KarXT, Karuna Therapeutics) achieves significant and clinically meaningful improvements in schizophrenia symptom scores without causing problematic adverse effects, new research suggests.

Results from the phase 3 EMERGENT-2 trial, which included more than 250 patients with schizophrenia, showed that those who received xanomeline-trospium for 5 weeks achieved a significant reduction in Positive and Negative Syndrome Scale (PANSS) total scores of more than nine points compared with their peers who received placebo. In addition, the improvements started at week 2.

Alongside significant reductions in both positive and negative symptoms, the results suggest the agent was well tolerated, with treatment-emergent adverse events (TEAEs) largely mild to moderate and transient in nature.

Lead investigator Christoph U. Correll, MD, professor of psychiatry at the Zucker School of Medicine at Hofstra/Northwell, Uniondale, New York, told this news organization that the upcoming EMERGENT-3 study will have a “European component” and that the “readout is expected most likely in the first quarter of next year.”

Dr. Correll suggested that if leads to “two positive studies and reasonable safety,” the novel agent may become part of the “next generation of antipsychotics that are not related to postsynaptic dopamine blockade.”

The findings for EMERGENT-2, presented at the 35th European College of Neuropsychopharmacology (ECNP) Congress as a poster and as an oral presentation, were an update of topline results released earlier this year.
 

Novel compound

Xanomeline-trospium is a novel compound that combines the dual M1/M4-preferring muscarinic receptor agonist effect of xanomeline with the peripherally restricted muscarinic receptor antagonist effect of trospium.

A previous phase 2 trial that compared the drug with placebo in almost 200 patients suggested it significantly reduced psychosis symptoms, leading to the current phase 3 trial.

Dr. Correll noted that xanomeline-trospium reduces psychosis via a “bottom up and top down approach.”

He said that on one hand, M4 agonism decreases acetylcholine in the ventral tegmental area and the associated stratum, “which then decreases dopamine levels from the bottom up,” while the M1 agonism stimulates GABA and decreases dopamine from the “top down.”

M1 agonism, however, also stimulates the cholinergic system peripherally, “which can give you nausea, vomiting, and also some blood pressure and pulse” problems, Dr. Correll said.

That was the limitation when this approach was studied by Lilly as a treatment for patients with Alzheimer’s disease, but the addition of trospium means “you’re buffering somewhat the cholinergic peripheral effects,” he said.

While that can conversely lead to dyspepsia, dry mouth, and constipation, Dr. Correll noted that the adverse effects of the novel agent are “mitigated by titration,” with patients taking up to 8 days to reach the full dose.

The result is that the drug was “overall tolerated, and the effect sizes were quite astounding,” he reported.
 

Intermittent, time limited TEAEs

The current trial included 252 patients aged 18-65 years (mean age, 45 years) who were confirmed to have schizophrenia and who had recently experienced a worsening of psychotic symptoms that warranted hospitalization. Three-quarters of the participants were men, and a similar proportion were Black. Approximately one quarter were White.

All were randomly assigned in a 1:1 ratio to receive either xanomeline-trospium or placebo following a 2-week screening period.

Xanomeline and trospium were titrated from 50 mg/20 mg twice daily to 125 mg/30 mg twice daily, and patients were treated for a total of 5 weeks. Efficacy and safety analyses were conducted in those who had received at least one dose of the study drug.

At the end of the treatment period, xanomeline-trospium was associated with a significant 9.6-point reduction in PANSS total scores relative to placebo; scores fell by 21.2 points with the active treatment, vs. 11.6 points with placebo (P < .0001).

The significant improvement in PANSS total score began at week 2 (P < .05) and continued to accrue over the course of the study.

Xanomeline-trospium was also associated with significant reductions in PANSS positive subscale scores in comparison with placebo (P < .0001), as well as with reductions in PANSS negative subscale scores (P < .01) and PANSS Marder negative subscale scores (P < .01).

Although 75.4% of patients who received xanomeline-trospium experienced a TEAE, in comparison with 58.4% of the placebo group, very few experienced a serious TEAE (just 1.6% in both groups).

TEAEs leading to discontinuation occurred in 7.1% of the active-treatment group, vs. 5.6% of the placebo group. The overall discontinuation rates from the trial were 25% and 21%, respectively.

The most common TEAEs with xanomeline-trospium were constipation (21.4%), dyspepsia (19.0%), nausea (19.0%), vomiting (14.3%), and headache (13.5%).

The results showed that cholinergic TEAEs typically began within the first 2 weeks of treatment and were “intermittent and time limited in nature,” the investigators noted. Moreover, average blood pressure levels were “similar” between the xanomeline-trospium and placebo groups “at each time point throughout the trial,” they added.

Dr. Correll reported that whereas the EMERGENT studies are testing xanomeline-trospium as a monotherapy, the ARISE program will be examining it as an “augmentation” treatment. “And that’s relevant because, let’s face it, patients do not switch” treatments, he said.

He suggested that if xanomeline-trospium is able to have a synergistic effect with other drugs, “we might be able to treat people who are currently not benefiting enough from postsynaptic dopamine blockade to maybe get a little bit closer” to the benefits seen with clozapine, which “also has problematic side effects.”
 

‘Really revolutionary’

Following the oral presentation of the study by coauthor Stephen K. Brannan, MD, chief medical officer, Karuna Therapeutics, Boston, the results were warmly received.

Session cochair Mark Weiser, MD, chairman at the department of psychiatry, Sackler School of Medicine, Tel Aviv University, Israel, said the agent is “really revolutionary in the field.

“It’s a non-dopamine compound which helps for schizophrenia, so we’re all very optimistic about it,” Dr. Weiser added.

Nevertheless, he asked Dr. Brannan whether the occurrence of gastrointestinal adverse effects with xanomeline-trospium led to “functional unblinding of the study.”

Dr. Brannan answered that the investigators were “really worried about this prior to EMERGENT-1” but that formal testing suggested it was not a problem.

Dr. Brannan said that although this has not yet been formally tested for the current trial, he believes that it is “highly unlikely” that functional unblinding occurred, inasmuch as the “percentages are about in the same range as we saw in EMERGENT-1.”

Speaking to ECNP Congress Daily in a conference roundup video, session cochair Andreas Reif, MD, PhD, professor of psychiatry, psychosomatic medicine, and psychotherapy at the University Hospital of Frankfurt (Germany), also highlighted the study.

He said that along with a study of dexmedetomidine sublingual film for agitation associated with schizophrenia or bipolar disorder that was also presented in the session, the current trial is “pivotal.”

Dr. Reif noted that the effect size shown with xanomeline-trospium was “really amazing.”

“We are in a really exciting time in treating mental disorders,” he said. “Industry is finally investing again, and really has new compounds that will make it to the market.”

Karuna plans to submit a new drug application with the Food and Drug Administration for KarXT in mid-2023. The drug is also in development for the treatment of psychiatric and neurologic conditions other than schizophrenia, including Alzheimer’s disease.

The study was funded by Karuna Therapeutics. Dr. Correll has reported relationships with Karuna, as well as AbbVie, Acadia, Alkermes, Allergan, Angelini, Aristo, Axsome, Boehringer-Ingelheim, Cardio Diagnostics, Cerevel, CNX Therapeutics, Compass Pathways, Damitsa, Gedeon Richter, Hikma, Holmusk, IntraCellular Therapies, Janssen/J&J, LB Pharma, Lundbeck, MedAvante-ProPhase, MedInCell, Medscape, Merck, Mindpax, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Newron, Noven, Otsuka, Pfizer, Pharmabrain, PPD Biotech, Recordati, Relmada, Reviva, Rovi, Seqirus, Servier, SK Life Science, Sumitomo Dainippon, Sunovion, Sun Pharma, Supernus, Takeda, Teva, Viatris, Otsuka, and UpToDate.

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

VIENNA – The investigational agent xanomeline-trospium (KarXT, Karuna Therapeutics) achieves significant and clinically meaningful improvements in schizophrenia symptom scores without causing problematic adverse effects, new research suggests.

Results from the phase 3 EMERGENT-2 trial, which included more than 250 patients with schizophrenia, showed that those who received xanomeline-trospium for 5 weeks achieved a significant reduction in Positive and Negative Syndrome Scale (PANSS) total scores of more than nine points compared with their peers who received placebo. In addition, the improvements started at week 2.

Alongside significant reductions in both positive and negative symptoms, the results suggest the agent was well tolerated, with treatment-emergent adverse events (TEAEs) largely mild to moderate and transient in nature.

Lead investigator Christoph U. Correll, MD, professor of psychiatry at the Zucker School of Medicine at Hofstra/Northwell, Uniondale, New York, told this news organization that the upcoming EMERGENT-3 study will have a “European component” and that the “readout is expected most likely in the first quarter of next year.”

Dr. Correll suggested that if leads to “two positive studies and reasonable safety,” the novel agent may become part of the “next generation of antipsychotics that are not related to postsynaptic dopamine blockade.”

The findings for EMERGENT-2, presented at the 35th European College of Neuropsychopharmacology (ECNP) Congress as a poster and as an oral presentation, were an update of topline results released earlier this year.
 

Novel compound

Xanomeline-trospium is a novel compound that combines the dual M1/M4-preferring muscarinic receptor agonist effect of xanomeline with the peripherally restricted muscarinic receptor antagonist effect of trospium.

A previous phase 2 trial that compared the drug with placebo in almost 200 patients suggested it significantly reduced psychosis symptoms, leading to the current phase 3 trial.

Dr. Correll noted that xanomeline-trospium reduces psychosis via a “bottom up and top down approach.”

He said that on one hand, M4 agonism decreases acetylcholine in the ventral tegmental area and the associated stratum, “which then decreases dopamine levels from the bottom up,” while the M1 agonism stimulates GABA and decreases dopamine from the “top down.”

M1 agonism, however, also stimulates the cholinergic system peripherally, “which can give you nausea, vomiting, and also some blood pressure and pulse” problems, Dr. Correll said.

That was the limitation when this approach was studied by Lilly as a treatment for patients with Alzheimer’s disease, but the addition of trospium means “you’re buffering somewhat the cholinergic peripheral effects,” he said.

While that can conversely lead to dyspepsia, dry mouth, and constipation, Dr. Correll noted that the adverse effects of the novel agent are “mitigated by titration,” with patients taking up to 8 days to reach the full dose.

The result is that the drug was “overall tolerated, and the effect sizes were quite astounding,” he reported.
 

Intermittent, time limited TEAEs

The current trial included 252 patients aged 18-65 years (mean age, 45 years) who were confirmed to have schizophrenia and who had recently experienced a worsening of psychotic symptoms that warranted hospitalization. Three-quarters of the participants were men, and a similar proportion were Black. Approximately one quarter were White.

All were randomly assigned in a 1:1 ratio to receive either xanomeline-trospium or placebo following a 2-week screening period.

Xanomeline and trospium were titrated from 50 mg/20 mg twice daily to 125 mg/30 mg twice daily, and patients were treated for a total of 5 weeks. Efficacy and safety analyses were conducted in those who had received at least one dose of the study drug.

At the end of the treatment period, xanomeline-trospium was associated with a significant 9.6-point reduction in PANSS total scores relative to placebo; scores fell by 21.2 points with the active treatment, vs. 11.6 points with placebo (P < .0001).

The significant improvement in PANSS total score began at week 2 (P < .05) and continued to accrue over the course of the study.

Xanomeline-trospium was also associated with significant reductions in PANSS positive subscale scores in comparison with placebo (P < .0001), as well as with reductions in PANSS negative subscale scores (P < .01) and PANSS Marder negative subscale scores (P < .01).

Although 75.4% of patients who received xanomeline-trospium experienced a TEAE, in comparison with 58.4% of the placebo group, very few experienced a serious TEAE (just 1.6% in both groups).

TEAEs leading to discontinuation occurred in 7.1% of the active-treatment group, vs. 5.6% of the placebo group. The overall discontinuation rates from the trial were 25% and 21%, respectively.

The most common TEAEs with xanomeline-trospium were constipation (21.4%), dyspepsia (19.0%), nausea (19.0%), vomiting (14.3%), and headache (13.5%).

The results showed that cholinergic TEAEs typically began within the first 2 weeks of treatment and were “intermittent and time limited in nature,” the investigators noted. Moreover, average blood pressure levels were “similar” between the xanomeline-trospium and placebo groups “at each time point throughout the trial,” they added.

Dr. Correll reported that whereas the EMERGENT studies are testing xanomeline-trospium as a monotherapy, the ARISE program will be examining it as an “augmentation” treatment. “And that’s relevant because, let’s face it, patients do not switch” treatments, he said.

He suggested that if xanomeline-trospium is able to have a synergistic effect with other drugs, “we might be able to treat people who are currently not benefiting enough from postsynaptic dopamine blockade to maybe get a little bit closer” to the benefits seen with clozapine, which “also has problematic side effects.”
 

‘Really revolutionary’

Following the oral presentation of the study by coauthor Stephen K. Brannan, MD, chief medical officer, Karuna Therapeutics, Boston, the results were warmly received.

Session cochair Mark Weiser, MD, chairman at the department of psychiatry, Sackler School of Medicine, Tel Aviv University, Israel, said the agent is “really revolutionary in the field.

“It’s a non-dopamine compound which helps for schizophrenia, so we’re all very optimistic about it,” Dr. Weiser added.

Nevertheless, he asked Dr. Brannan whether the occurrence of gastrointestinal adverse effects with xanomeline-trospium led to “functional unblinding of the study.”

Dr. Brannan answered that the investigators were “really worried about this prior to EMERGENT-1” but that formal testing suggested it was not a problem.

Dr. Brannan said that although this has not yet been formally tested for the current trial, he believes that it is “highly unlikely” that functional unblinding occurred, inasmuch as the “percentages are about in the same range as we saw in EMERGENT-1.”

Speaking to ECNP Congress Daily in a conference roundup video, session cochair Andreas Reif, MD, PhD, professor of psychiatry, psychosomatic medicine, and psychotherapy at the University Hospital of Frankfurt (Germany), also highlighted the study.

He said that along with a study of dexmedetomidine sublingual film for agitation associated with schizophrenia or bipolar disorder that was also presented in the session, the current trial is “pivotal.”

Dr. Reif noted that the effect size shown with xanomeline-trospium was “really amazing.”

“We are in a really exciting time in treating mental disorders,” he said. “Industry is finally investing again, and really has new compounds that will make it to the market.”

Karuna plans to submit a new drug application with the Food and Drug Administration for KarXT in mid-2023. The drug is also in development for the treatment of psychiatric and neurologic conditions other than schizophrenia, including Alzheimer’s disease.

The study was funded by Karuna Therapeutics. Dr. Correll has reported relationships with Karuna, as well as AbbVie, Acadia, Alkermes, Allergan, Angelini, Aristo, Axsome, Boehringer-Ingelheim, Cardio Diagnostics, Cerevel, CNX Therapeutics, Compass Pathways, Damitsa, Gedeon Richter, Hikma, Holmusk, IntraCellular Therapies, Janssen/J&J, LB Pharma, Lundbeck, MedAvante-ProPhase, MedInCell, Medscape, Merck, Mindpax, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Newron, Noven, Otsuka, Pfizer, Pharmabrain, PPD Biotech, Recordati, Relmada, Reviva, Rovi, Seqirus, Servier, SK Life Science, Sumitomo Dainippon, Sunovion, Sun Pharma, Supernus, Takeda, Teva, Viatris, Otsuka, and UpToDate.

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

The first in what have come to be known as the “wrong stitches” cases has been settled, a story in The Ledger reports.

The former plaintiff in the now-settled suit is Carrie Monk, a Lakeland, Fla., resident who underwent total laparoscopic hysterectomy at Lakeland Regional Health Medical Center several years ago. (The medical center is managed by Lakeland Regional Health Systems.) During that procedure, Ms. Monk claimed, her doctors used permanent rather than absorbable sutures to close her incisions. As a result, over the next 19 months, she experienced abdominal pain and constant bleeding, which in turn affected her personal life as well as her work as a nurse in the intensive care unit. She underwent follow-up surgery to have the permanent sutures removed, but two could not be identified and excised.

In July 2020, Ms. Monk filed a medical malpractice claim against Lakeland Regional Health, its medical center, and the ob-gyns who had performed her surgery. She was among the first of the women who had received the permanent sutures to do so.

On February 28, 2021, The Ledger ran a story on Ms. Monk’s suit. Less than 2 weeks later, Lakeland Regional Health sent letters to patients who had undergone “wrong stitch” surgeries, cautioning of possible postsurgical complications. The company reportedly kept secret how many letters it had sent out.

Since then, at least nine similar suits have been filed against Lakeland Regional Health, bringing the total number of such suits to 12. Four of these suits have been settled, including Ms. Monk’s. Of the remaining eight cases, several are in various pretrial stages.

Under the terms of her settlement, neither Ms. Monk nor her attorney may disclose what financial compensation or other awards she’s received. The attorney, however, referred to the settlement as “amicable.”

The content contained in this article is for informational purposes only and does not constitute legal advice. Reliance on any information provided in this article is solely at your own risk.

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

The first in what have come to be known as the “wrong stitches” cases has been settled, a story in The Ledger reports.

The former plaintiff in the now-settled suit is Carrie Monk, a Lakeland, Fla., resident who underwent total laparoscopic hysterectomy at Lakeland Regional Health Medical Center several years ago. (The medical center is managed by Lakeland Regional Health Systems.) During that procedure, Ms. Monk claimed, her doctors used permanent rather than absorbable sutures to close her incisions. As a result, over the next 19 months, she experienced abdominal pain and constant bleeding, which in turn affected her personal life as well as her work as a nurse in the intensive care unit. She underwent follow-up surgery to have the permanent sutures removed, but two could not be identified and excised.

In July 2020, Ms. Monk filed a medical malpractice claim against Lakeland Regional Health, its medical center, and the ob-gyns who had performed her surgery. She was among the first of the women who had received the permanent sutures to do so.

On February 28, 2021, The Ledger ran a story on Ms. Monk’s suit. Less than 2 weeks later, Lakeland Regional Health sent letters to patients who had undergone “wrong stitch” surgeries, cautioning of possible postsurgical complications. The company reportedly kept secret how many letters it had sent out.

Since then, at least nine similar suits have been filed against Lakeland Regional Health, bringing the total number of such suits to 12. Four of these suits have been settled, including Ms. Monk’s. Of the remaining eight cases, several are in various pretrial stages.

Under the terms of her settlement, neither Ms. Monk nor her attorney may disclose what financial compensation or other awards she’s received. The attorney, however, referred to the settlement as “amicable.”

The content contained in this article is for informational purposes only and does not constitute legal advice. Reliance on any information provided in this article is solely at your own risk.

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

The first in what have come to be known as the “wrong stitches” cases has been settled, a story in The Ledger reports.

The former plaintiff in the now-settled suit is Carrie Monk, a Lakeland, Fla., resident who underwent total laparoscopic hysterectomy at Lakeland Regional Health Medical Center several years ago. (The medical center is managed by Lakeland Regional Health Systems.) During that procedure, Ms. Monk claimed, her doctors used permanent rather than absorbable sutures to close her incisions. As a result, over the next 19 months, she experienced abdominal pain and constant bleeding, which in turn affected her personal life as well as her work as a nurse in the intensive care unit. She underwent follow-up surgery to have the permanent sutures removed, but two could not be identified and excised.

In July 2020, Ms. Monk filed a medical malpractice claim against Lakeland Regional Health, its medical center, and the ob-gyns who had performed her surgery. She was among the first of the women who had received the permanent sutures to do so.

On February 28, 2021, The Ledger ran a story on Ms. Monk’s suit. Less than 2 weeks later, Lakeland Regional Health sent letters to patients who had undergone “wrong stitch” surgeries, cautioning of possible postsurgical complications. The company reportedly kept secret how many letters it had sent out.

Since then, at least nine similar suits have been filed against Lakeland Regional Health, bringing the total number of such suits to 12. Four of these suits have been settled, including Ms. Monk’s. Of the remaining eight cases, several are in various pretrial stages.

Under the terms of her settlement, neither Ms. Monk nor her attorney may disclose what financial compensation or other awards she’s received. The attorney, however, referred to the settlement as “amicable.”

The content contained in this article is for informational purposes only and does not constitute legal advice. Reliance on any information provided in this article is solely at your own risk.

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

Pediatric patients with epilepsy have an increased risk of cardiovascular complications later in life, but little is known about how they progress. A new study finds that abnormalities in electrocardiograms are linked to an earlier age of diagnosis and longer epilepsy duration.

The findings could help researchers in the search for biomarkers that could predict later problems in children with epilepsy. “In pediatric neurology I think we’re a little bit removed from some of the cardiovascular complications that can happen within epilepsy, but cardiovascular complications are well established, especially in adults that have epilepsy. Adults with epilepsy are more likely to have coronary artery disease, atherosclerosis, arrhythmias, heart attacks, and sudden cardiac death. It’s a pretty substantial difference compared with their nonepileptic peers. So knowing that, the big question is, how do these changes develop, and how do we really counsel our patients in regards to these complications?” said Brittnie Bartlett, MD, during her presentation of the research at the 2022 annual meeting of the Child Neurology Society.

Identifying factors that increase cardiac complications

Previous studies suggested that epilepsy duration might be linked to cardiovascular complications. In children with Dravet syndrome, epilepsy duration has been shown to be associated with cardiac complications. Pathological T wave alternans, which indicates ventricular instability, has been observed in adults with longstanding epilepsy but not adults with newly diagnosed epilepsy.

“So our question in this preliminary report of our data is: What factors in our general pediatric epilepsy cohort can we identify that put them at a greater risk for having EKG changes, and specifically, we wanted to verify these findings from the other studies that epilepsy duration is, in fact, a risk factor for these EKG changes in general [among children] with epilepsy aside from channelopathies,” said Dr. Bartlett, who is an assistant professor at Baylor College of Medicine and a child neurologist at Texas Children’s Hospital, both in Houston.

She presented a striking finding that cardiovascular changes appear early. “The most important thing I want you all to make note of is the fact that, in this baseline study that we got on these kids, 47% already had changes that we were seeing on their EKGs,” said Dr. Bartlett.

The researchers also looked for factors associated with EKG changes, and found that duration of epilepsy and age at diagnosis were the two salient factors. “Our kids that did have EKG changes present had an average epilepsy duration of 73 months, as opposed to [the children] that did not have EKG changes and had an average epilepsy duration of 46 months,” said Dr. Bartlett.

Other factors, such epilepsy type, etiology, refractory epilepsy, and seizure frequency had no statistically significant association with EKG changes. They also saw no associations with high-risk seizure medications, even though some antiseizure drugs have been shown to be linked to EKG changes.

“We were able to confirm our hypothesis that EKG changes were more prevalent with longer duration of epilepsy. Unfortunately, we weren’t able to find any other clues that would help us counsel our patients, but this is part of a longitudinal prospective study that we’ll be following these kids over a couple of years’ time, so maybe we’ll be able to tease out some of these differences. Ideally, we’d be able to find some kind of a biomarker for future cardiovascular complications, and right now we’re working with some multivariable models to verify some of these findings,” said Dr. Bartlett.

Implications for clinical practice

During the Q&A, Dr. Bartlett was asked if all kids with epilepsy should undergo an EKG. She recommended against it for now. “At this point, I don’t think we have enough clear data to support getting an EKG on every kid with epilepsy. I do think it’s good practice to do them on all kids with channelopathies. As a general practice, I tend to have a low threshold towards many kids with epilepsy, but a lot of these cardiovascular risk factors tend to pop up more in adulthood, so it’s more preventative,” she said.

Grace Gombolay, MD, who moderated the session where the poster was presented, was asked for comment on the study. “What’s surprising about it is that up to half of patients actually had EKG changes, different what from what we see in normal population, and it’s interesting to think about the implications. One of the things that our epilepsy patients are at risk for is SUDEP – sudden, unexplained death in epilepsy. It’s interesting to think about what these EKG changes mean for clinical care. I think it’s too early to say at this time, but this might be one of those markers for SUDEP,” said Dr. Gombolay, who is an assistant professor at Emory University, Atlanta, and director of the Pediatric Neuroimmunology and Multiple Sclerosis Clinic at Children’s Healthcare of Atlanta.

The researchers prospectively studied 213 patients who were recruited. 46% were female, 42% were white, 41% were Hispanic, and 13% were African American. The mean age at enrollment was 116 months, and mean age of seizure onset was 45 months.

The researchers found that 47% had abnormal EKG readings. None of the changes were pathologic, but they may reflect changes to cardiac electrophysiology, according to Dr. Bartlett. Those with abnormal readings were older on average (11.6 vs. 8.3 years; P < .005) and had a longer epilepsy duration (73 vs. 46 months; P = .004).

Dr. Gombolay has no relevant financial disclosures.

Pediatric patients with epilepsy have an increased risk of cardiovascular complications later in life, but little is known about how they progress. A new study finds that abnormalities in electrocardiograms are linked to an earlier age of diagnosis and longer epilepsy duration.

The findings could help researchers in the search for biomarkers that could predict later problems in children with epilepsy. “In pediatric neurology I think we’re a little bit removed from some of the cardiovascular complications that can happen within epilepsy, but cardiovascular complications are well established, especially in adults that have epilepsy. Adults with epilepsy are more likely to have coronary artery disease, atherosclerosis, arrhythmias, heart attacks, and sudden cardiac death. It’s a pretty substantial difference compared with their nonepileptic peers. So knowing that, the big question is, how do these changes develop, and how do we really counsel our patients in regards to these complications?” said Brittnie Bartlett, MD, during her presentation of the research at the 2022 annual meeting of the Child Neurology Society.

Identifying factors that increase cardiac complications

Previous studies suggested that epilepsy duration might be linked to cardiovascular complications. In children with Dravet syndrome, epilepsy duration has been shown to be associated with cardiac complications. Pathological T wave alternans, which indicates ventricular instability, has been observed in adults with longstanding epilepsy but not adults with newly diagnosed epilepsy.

“So our question in this preliminary report of our data is: What factors in our general pediatric epilepsy cohort can we identify that put them at a greater risk for having EKG changes, and specifically, we wanted to verify these findings from the other studies that epilepsy duration is, in fact, a risk factor for these EKG changes in general [among children] with epilepsy aside from channelopathies,” said Dr. Bartlett, who is an assistant professor at Baylor College of Medicine and a child neurologist at Texas Children’s Hospital, both in Houston.

She presented a striking finding that cardiovascular changes appear early. “The most important thing I want you all to make note of is the fact that, in this baseline study that we got on these kids, 47% already had changes that we were seeing on their EKGs,” said Dr. Bartlett.

The researchers also looked for factors associated with EKG changes, and found that duration of epilepsy and age at diagnosis were the two salient factors. “Our kids that did have EKG changes present had an average epilepsy duration of 73 months, as opposed to [the children] that did not have EKG changes and had an average epilepsy duration of 46 months,” said Dr. Bartlett.

Other factors, such epilepsy type, etiology, refractory epilepsy, and seizure frequency had no statistically significant association with EKG changes. They also saw no associations with high-risk seizure medications, even though some antiseizure drugs have been shown to be linked to EKG changes.

“We were able to confirm our hypothesis that EKG changes were more prevalent with longer duration of epilepsy. Unfortunately, we weren’t able to find any other clues that would help us counsel our patients, but this is part of a longitudinal prospective study that we’ll be following these kids over a couple of years’ time, so maybe we’ll be able to tease out some of these differences. Ideally, we’d be able to find some kind of a biomarker for future cardiovascular complications, and right now we’re working with some multivariable models to verify some of these findings,” said Dr. Bartlett.

Implications for clinical practice

During the Q&A, Dr. Bartlett was asked if all kids with epilepsy should undergo an EKG. She recommended against it for now. “At this point, I don’t think we have enough clear data to support getting an EKG on every kid with epilepsy. I do think it’s good practice to do them on all kids with channelopathies. As a general practice, I tend to have a low threshold towards many kids with epilepsy, but a lot of these cardiovascular risk factors tend to pop up more in adulthood, so it’s more preventative,” she said.

Grace Gombolay, MD, who moderated the session where the poster was presented, was asked for comment on the study. “What’s surprising about it is that up to half of patients actually had EKG changes, different what from what we see in normal population, and it’s interesting to think about the implications. One of the things that our epilepsy patients are at risk for is SUDEP – sudden, unexplained death in epilepsy. It’s interesting to think about what these EKG changes mean for clinical care. I think it’s too early to say at this time, but this might be one of those markers for SUDEP,” said Dr. Gombolay, who is an assistant professor at Emory University, Atlanta, and director of the Pediatric Neuroimmunology and Multiple Sclerosis Clinic at Children’s Healthcare of Atlanta.

The researchers prospectively studied 213 patients who were recruited. 46% were female, 42% were white, 41% were Hispanic, and 13% were African American. The mean age at enrollment was 116 months, and mean age of seizure onset was 45 months.

The researchers found that 47% had abnormal EKG readings. None of the changes were pathologic, but they may reflect changes to cardiac electrophysiology, according to Dr. Bartlett. Those with abnormal readings were older on average (11.6 vs. 8.3 years; P < .005) and had a longer epilepsy duration (73 vs. 46 months; P = .004).

Dr. Gombolay has no relevant financial disclosures.

Pediatric patients with epilepsy have an increased risk of cardiovascular complications later in life, but little is known about how they progress. A new study finds that abnormalities in electrocardiograms are linked to an earlier age of diagnosis and longer epilepsy duration.

The findings could help researchers in the search for biomarkers that could predict later problems in children with epilepsy. “In pediatric neurology I think we’re a little bit removed from some of the cardiovascular complications that can happen within epilepsy, but cardiovascular complications are well established, especially in adults that have epilepsy. Adults with epilepsy are more likely to have coronary artery disease, atherosclerosis, arrhythmias, heart attacks, and sudden cardiac death. It’s a pretty substantial difference compared with their nonepileptic peers. So knowing that, the big question is, how do these changes develop, and how do we really counsel our patients in regards to these complications?” said Brittnie Bartlett, MD, during her presentation of the research at the 2022 annual meeting of the Child Neurology Society.

Identifying factors that increase cardiac complications

Previous studies suggested that epilepsy duration might be linked to cardiovascular complications. In children with Dravet syndrome, epilepsy duration has been shown to be associated with cardiac complications. Pathological T wave alternans, which indicates ventricular instability, has been observed in adults with longstanding epilepsy but not adults with newly diagnosed epilepsy.

“So our question in this preliminary report of our data is: What factors in our general pediatric epilepsy cohort can we identify that put them at a greater risk for having EKG changes, and specifically, we wanted to verify these findings from the other studies that epilepsy duration is, in fact, a risk factor for these EKG changes in general [among children] with epilepsy aside from channelopathies,” said Dr. Bartlett, who is an assistant professor at Baylor College of Medicine and a child neurologist at Texas Children’s Hospital, both in Houston.

She presented a striking finding that cardiovascular changes appear early. “The most important thing I want you all to make note of is the fact that, in this baseline study that we got on these kids, 47% already had changes that we were seeing on their EKGs,” said Dr. Bartlett.

The researchers also looked for factors associated with EKG changes, and found that duration of epilepsy and age at diagnosis were the two salient factors. “Our kids that did have EKG changes present had an average epilepsy duration of 73 months, as opposed to [the children] that did not have EKG changes and had an average epilepsy duration of 46 months,” said Dr. Bartlett.

Other factors, such epilepsy type, etiology, refractory epilepsy, and seizure frequency had no statistically significant association with EKG changes. They also saw no associations with high-risk seizure medications, even though some antiseizure drugs have been shown to be linked to EKG changes.

“We were able to confirm our hypothesis that EKG changes were more prevalent with longer duration of epilepsy. Unfortunately, we weren’t able to find any other clues that would help us counsel our patients, but this is part of a longitudinal prospective study that we’ll be following these kids over a couple of years’ time, so maybe we’ll be able to tease out some of these differences. Ideally, we’d be able to find some kind of a biomarker for future cardiovascular complications, and right now we’re working with some multivariable models to verify some of these findings,” said Dr. Bartlett.

Implications for clinical practice

During the Q&A, Dr. Bartlett was asked if all kids with epilepsy should undergo an EKG. She recommended against it for now. “At this point, I don’t think we have enough clear data to support getting an EKG on every kid with epilepsy. I do think it’s good practice to do them on all kids with channelopathies. As a general practice, I tend to have a low threshold towards many kids with epilepsy, but a lot of these cardiovascular risk factors tend to pop up more in adulthood, so it’s more preventative,” she said.

Grace Gombolay, MD, who moderated the session where the poster was presented, was asked for comment on the study. “What’s surprising about it is that up to half of patients actually had EKG changes, different what from what we see in normal population, and it’s interesting to think about the implications. One of the things that our epilepsy patients are at risk for is SUDEP – sudden, unexplained death in epilepsy. It’s interesting to think about what these EKG changes mean for clinical care. I think it’s too early to say at this time, but this might be one of those markers for SUDEP,” said Dr. Gombolay, who is an assistant professor at Emory University, Atlanta, and director of the Pediatric Neuroimmunology and Multiple Sclerosis Clinic at Children’s Healthcare of Atlanta.

The researchers prospectively studied 213 patients who were recruited. 46% were female, 42% were white, 41% were Hispanic, and 13% were African American. The mean age at enrollment was 116 months, and mean age of seizure onset was 45 months.

The researchers found that 47% had abnormal EKG readings. None of the changes were pathologic, but they may reflect changes to cardiac electrophysiology, according to Dr. Bartlett. Those with abnormal readings were older on average (11.6 vs. 8.3 years; P < .005) and had a longer epilepsy duration (73 vs. 46 months; P = .004).

Dr. Gombolay has no relevant financial disclosures.