Randy Dotinga

A new study offers fresh insight into early indications of high-risk, early-stage, epithelial ovarian cancer: More than 70% have at least one symptom such as abdominal/pelvic pain or increased girth/fullness, and women with larger tumors have more symptoms.

“Even in early-stage disease, ovarian cancer is not necessarily a silent disease,” said lead author and gynecologic oncologist/surgeon John K. Chan, MD, of Palo Alto Medical Foundation/California Pacific/Sutter Research Institute.

The study appeared online Jan. 6, in the journal Obstetrics & Gynecology.*

According to Dr. Chan, most previous studies of symptoms in ovarian cancer have focused on those with advanced disease since that’s when it’s typically diagnosed. “Given these gaps in knowledge from prior reports, we performed this analysis to evaluate the presentation and characteristic symptoms of early-stage ovarian cancer and to attempt to identify the relationship between these symptoms with respect to clinicopathologic characteristics and prognosis in early-stage disease.”

Dr. Chan and colleagues retrospectively tracked 419 patients who were subjects in a clinical trial of chemotherapy doses. The patients all had high-risk, early-stage epithelial ovarian cancer (stage IA-IB and grade 3, any clear cell, stage IC or II).

Of the patients, 40% presented with one symptom, while 32% had multiple symptoms. The other 28% had no symptoms, and their masses were diagnosed upon discovery during physical examination. “Other investigators have found that nearly 95% of patients with ovarian cancer were symptomatic,” Dr. Chan said. “The lower percentage of symptomatic patients in our study may be because all 419 patients had early-stage disease as opposed to advanced-stage disease.”

The most common symptoms were abdominal or pelvic pain (31%; 95% confidence interval, 27%-36%), fullness or increased abdominal girth (27%; 95% CI, 22%-31%), abnormal vaginal bleeding (13%; 95% CI, 10%-17%), urinary problems (10%; 95% CI, 8%-14%), and gastrointestinal problems (6%; 95% CI, 4%-8%).

There was no statistically significant link between number of symptoms and age (younger than 60 or 60 or older), cancer stage, or histologic subtype. However, patients with the largest tumors (>15 cm) were more likely to have multiple symptoms than those with the smallest tumors (10 cm or smaller): 46% vs. 21% (P < .001).

Also, 79% of those with the largest tumors (>15 cm) had at least one symptom, compared with 65% of those with the smallest tumors (10 cm or smaller, P < .001)

Unlike other studies, this report didn’t find a link between the number of symptoms and mortality. This finding surprised the researchers, Dr. Chan said, as did the lack of connections between symptoms and age, stage, or histologic subtype. “We were expecting that the younger patients may have more symptoms given the association with endometriosis and clear cell cancers,” he said. “We also thought that those who are less symptomatic may have more stage I and low-grade indolent tumors with better survival, but we did not find that.”

The researchers noted limitations such as the lack of standardization in the patient data.

In the big picture, Dr. Chan said, “patients and health care professionals need to have a higher index of suspicion in symptomatic ovarian cancer patients to increase early detection and potentially improve cures. Ovarian cancer does not always kill. In fact, up to 80% of our early-stage disease patients are cured.”

He called for “additional research to evaluate symptom awareness in early-stage cancers and possibly incorporating novel serum biomarkers and wearable monitoring devices. Wearables may be able to assess for frequency or duration of symptoms, which may be an important factor in distinguishing symptoms that are more concerning for ovarian cancer.”

In an adjoining commentary, Barbara A. Goff, MD, chair of obstetrics and gynecology at the University of Washington, Seattle, noted that, while ovarian cancers diagnosed early have a high survival rate, prospective randomized trials of transvaginal ultrasonography and tumor marker screening strategies have failed to reduce mortality. There’s currently no recommended screening test for women at average risk.

There are other challenges, she wrote. For one, “many health care professionals are seemingly unaware of the symptoms typically associated with ovarian cancer, so misdiagnosis remains common.” And “one of the concerns about the symptoms of ovarian cancer is that they can be vague and commonly present in the general population.”

Dr. Goff praised the study, called for more education about the symptoms of ovarian cancer, and wrote that “symptom recognition with appropriate diagnostic testing remains very important in our efforts to improve outcomes.”

The National Institutes of Health funded the study. Several study authors, including Dr. Chan, reported various disclosures.

Correction, 1/31/22: An earlier version of this article misstated the date of publication.

A new study offers fresh insight into early indications of high-risk, early-stage, epithelial ovarian cancer: More than 70% have at least one symptom such as abdominal/pelvic pain or increased girth/fullness, and women with larger tumors have more symptoms.

“Even in early-stage disease, ovarian cancer is not necessarily a silent disease,” said lead author and gynecologic oncologist/surgeon John K. Chan, MD, of Palo Alto Medical Foundation/California Pacific/Sutter Research Institute.

The study appeared online Jan. 6, in the journal Obstetrics & Gynecology.*

According to Dr. Chan, most previous studies of symptoms in ovarian cancer have focused on those with advanced disease since that’s when it’s typically diagnosed. “Given these gaps in knowledge from prior reports, we performed this analysis to evaluate the presentation and characteristic symptoms of early-stage ovarian cancer and to attempt to identify the relationship between these symptoms with respect to clinicopathologic characteristics and prognosis in early-stage disease.”

Dr. Chan and colleagues retrospectively tracked 419 patients who were subjects in a clinical trial of chemotherapy doses. The patients all had high-risk, early-stage epithelial ovarian cancer (stage IA-IB and grade 3, any clear cell, stage IC or II).

Of the patients, 40% presented with one symptom, while 32% had multiple symptoms. The other 28% had no symptoms, and their masses were diagnosed upon discovery during physical examination. “Other investigators have found that nearly 95% of patients with ovarian cancer were symptomatic,” Dr. Chan said. “The lower percentage of symptomatic patients in our study may be because all 419 patients had early-stage disease as opposed to advanced-stage disease.”

The most common symptoms were abdominal or pelvic pain (31%; 95% confidence interval, 27%-36%), fullness or increased abdominal girth (27%; 95% CI, 22%-31%), abnormal vaginal bleeding (13%; 95% CI, 10%-17%), urinary problems (10%; 95% CI, 8%-14%), and gastrointestinal problems (6%; 95% CI, 4%-8%).

There was no statistically significant link between number of symptoms and age (younger than 60 or 60 or older), cancer stage, or histologic subtype. However, patients with the largest tumors (>15 cm) were more likely to have multiple symptoms than those with the smallest tumors (10 cm or smaller): 46% vs. 21% (P < .001).

Also, 79% of those with the largest tumors (>15 cm) had at least one symptom, compared with 65% of those with the smallest tumors (10 cm or smaller, P < .001)

Unlike other studies, this report didn’t find a link between the number of symptoms and mortality. This finding surprised the researchers, Dr. Chan said, as did the lack of connections between symptoms and age, stage, or histologic subtype. “We were expecting that the younger patients may have more symptoms given the association with endometriosis and clear cell cancers,” he said. “We also thought that those who are less symptomatic may have more stage I and low-grade indolent tumors with better survival, but we did not find that.”

The researchers noted limitations such as the lack of standardization in the patient data.

In the big picture, Dr. Chan said, “patients and health care professionals need to have a higher index of suspicion in symptomatic ovarian cancer patients to increase early detection and potentially improve cures. Ovarian cancer does not always kill. In fact, up to 80% of our early-stage disease patients are cured.”

He called for “additional research to evaluate symptom awareness in early-stage cancers and possibly incorporating novel serum biomarkers and wearable monitoring devices. Wearables may be able to assess for frequency or duration of symptoms, which may be an important factor in distinguishing symptoms that are more concerning for ovarian cancer.”

In an adjoining commentary, Barbara A. Goff, MD, chair of obstetrics and gynecology at the University of Washington, Seattle, noted that, while ovarian cancers diagnosed early have a high survival rate, prospective randomized trials of transvaginal ultrasonography and tumor marker screening strategies have failed to reduce mortality. There’s currently no recommended screening test for women at average risk.

There are other challenges, she wrote. For one, “many health care professionals are seemingly unaware of the symptoms typically associated with ovarian cancer, so misdiagnosis remains common.” And “one of the concerns about the symptoms of ovarian cancer is that they can be vague and commonly present in the general population.”

Dr. Goff praised the study, called for more education about the symptoms of ovarian cancer, and wrote that “symptom recognition with appropriate diagnostic testing remains very important in our efforts to improve outcomes.”

The National Institutes of Health funded the study. Several study authors, including Dr. Chan, reported various disclosures.

Correction, 1/31/22: An earlier version of this article misstated the date of publication.

A new study offers fresh insight into early indications of high-risk, early-stage, epithelial ovarian cancer: More than 70% have at least one symptom such as abdominal/pelvic pain or increased girth/fullness, and women with larger tumors have more symptoms.

“Even in early-stage disease, ovarian cancer is not necessarily a silent disease,” said lead author and gynecologic oncologist/surgeon John K. Chan, MD, of Palo Alto Medical Foundation/California Pacific/Sutter Research Institute.

The study appeared online Jan. 6, in the journal Obstetrics & Gynecology.*

According to Dr. Chan, most previous studies of symptoms in ovarian cancer have focused on those with advanced disease since that’s when it’s typically diagnosed. “Given these gaps in knowledge from prior reports, we performed this analysis to evaluate the presentation and characteristic symptoms of early-stage ovarian cancer and to attempt to identify the relationship between these symptoms with respect to clinicopathologic characteristics and prognosis in early-stage disease.”

Dr. Chan and colleagues retrospectively tracked 419 patients who were subjects in a clinical trial of chemotherapy doses. The patients all had high-risk, early-stage epithelial ovarian cancer (stage IA-IB and grade 3, any clear cell, stage IC or II).

Of the patients, 40% presented with one symptom, while 32% had multiple symptoms. The other 28% had no symptoms, and their masses were diagnosed upon discovery during physical examination. “Other investigators have found that nearly 95% of patients with ovarian cancer were symptomatic,” Dr. Chan said. “The lower percentage of symptomatic patients in our study may be because all 419 patients had early-stage disease as opposed to advanced-stage disease.”

The most common symptoms were abdominal or pelvic pain (31%; 95% confidence interval, 27%-36%), fullness or increased abdominal girth (27%; 95% CI, 22%-31%), abnormal vaginal bleeding (13%; 95% CI, 10%-17%), urinary problems (10%; 95% CI, 8%-14%), and gastrointestinal problems (6%; 95% CI, 4%-8%).

There was no statistically significant link between number of symptoms and age (younger than 60 or 60 or older), cancer stage, or histologic subtype. However, patients with the largest tumors (>15 cm) were more likely to have multiple symptoms than those with the smallest tumors (10 cm or smaller): 46% vs. 21% (P < .001).

Also, 79% of those with the largest tumors (>15 cm) had at least one symptom, compared with 65% of those with the smallest tumors (10 cm or smaller, P < .001)

Unlike other studies, this report didn’t find a link between the number of symptoms and mortality. This finding surprised the researchers, Dr. Chan said, as did the lack of connections between symptoms and age, stage, or histologic subtype. “We were expecting that the younger patients may have more symptoms given the association with endometriosis and clear cell cancers,” he said. “We also thought that those who are less symptomatic may have more stage I and low-grade indolent tumors with better survival, but we did not find that.”

The researchers noted limitations such as the lack of standardization in the patient data.

In the big picture, Dr. Chan said, “patients and health care professionals need to have a higher index of suspicion in symptomatic ovarian cancer patients to increase early detection and potentially improve cures. Ovarian cancer does not always kill. In fact, up to 80% of our early-stage disease patients are cured.”

He called for “additional research to evaluate symptom awareness in early-stage cancers and possibly incorporating novel serum biomarkers and wearable monitoring devices. Wearables may be able to assess for frequency or duration of symptoms, which may be an important factor in distinguishing symptoms that are more concerning for ovarian cancer.”

In an adjoining commentary, Barbara A. Goff, MD, chair of obstetrics and gynecology at the University of Washington, Seattle, noted that, while ovarian cancers diagnosed early have a high survival rate, prospective randomized trials of transvaginal ultrasonography and tumor marker screening strategies have failed to reduce mortality. There’s currently no recommended screening test for women at average risk.

There are other challenges, she wrote. For one, “many health care professionals are seemingly unaware of the symptoms typically associated with ovarian cancer, so misdiagnosis remains common.” And “one of the concerns about the symptoms of ovarian cancer is that they can be vague and commonly present in the general population.”

Dr. Goff praised the study, called for more education about the symptoms of ovarian cancer, and wrote that “symptom recognition with appropriate diagnostic testing remains very important in our efforts to improve outcomes.”

The National Institutes of Health funded the study. Several study authors, including Dr. Chan, reported various disclosures.

Correction, 1/31/22: An earlier version of this article misstated the date of publication.

A new, augmented autism-screening strategy boosted the number of boys diagnosed with the condition, especially Spanish speakers, a new study finds. The research was published in JAMA Pediatrics

The number of diagnoses in girls didn’t budge significantly, however, surprising researchers. Still, the findings suggest that “multistage screening and appropriate access to diagnostic services can really move the needle on the early detection of autism and reducing disparities in autism diagnosis and detection,” said lead author R. Christopher Sheldrick, PhD, a Boston University research associate professor of health law, policy, and management, in an interview.

While early intervention is considered crucial, U.S. research suggests that several groups of children – the poor, racial and ethnic minorities, and non-English speakers – are more likely to be diagnosed with autism spectrum disorder (ASD) later in life. “They have much lower access to appropriate services, both to get kids diagnosed and to get the kinds of interventions that can be helpful for families,” Dr. Sheldrick said. “Our study is about trying to close the gap around diagnosis, the first step.”

For the new study, the researchers implemented an intervention strategy in Massachusetts at three Early Intervention (EI) programs, which provide autism screening to children who are referred by pediatricians or parents. The researchers then tracked the programs, all in Boston, and nine comparison programs from the greater Boston area from 2012 to 2018.

Overall, 33,326 children were assessed, all aged 14-36 months. Those at the intervention programs were chosen because they had high levels of poverty. Children at those programs were more likely to be Black than those at the comparison programs (30.7% vs. 12.2%), to be Spanish speakers (28.9% vs. 12.5%), and to be in the lowest household income bracket (66.9% vs. 54.2%). In both groups, about 64% of the children were male.

The intervention strategy aimed to reduce the reliance on screening tests. Instead, the study authors write, “our protocol emphasizes ASD screening as a process that includes clinician and parent decision-making.”

As Dr. Sheldrick explained, parents and specialists observe children together “and then decide whether it’s worth taking the next step, which is a full diagnostic assessment with a licensed professional.” According to the study, either the parent(s) or the specialists could make the referral for a full, university-based assessment.

The goal was to help specialists use their professional judgment more, he said, and refer children who don’t show signs of ASD via a screening instrument but still spark concern, he said. “We’re really trying to create a system in which the screening tools support professional judgment, but don’t really replace it.”

After weighting, the researchers found that diagnoses of ASD were more common in the intervention sites vs. comparison sites (incidence rate ratio, 1.6; 95% confidence interval, 1.3-2.1, P < .001), accounting for an extra 8.1 diagnoses per 1,000 per quarter. Among Spanish-speaking families only, diagnoses grew even more in the intervention sites vs. comparison sites (IRR, 2.6; 95% CI, 1.6-4.3; P < .001), representing 15.4 additional diagnoses per 1,000 children per quarter.

There was also an increase in diagnoses among boys in the intervention sites vs. comparison sites (IRR, 1.8; 95% CI, 1.4-2.3; P < .001), accounting for 14.8 additional diagnoses per 1,000 children per quarter. However, there was no statistically significant increase in diagnosis among girls (IRR, 1.1; 95% CI, 0.6-1.7; P = .84).

The finding about girls surprised the researchers. “The program was highly effective for boys, but really didn’t have any effect for girls,” Dr. Sheldrick said. “Even though autism is considered to be more common in boys, there are questions about whether it’s underidentified in girls. These data would be consistent with that view. So there’s work to do to be able to recognize how a young girl with autism might present and how you might note that in a sensitive way and then respond appropriately.”

The overall message of the study is “that screening with appropriate supports can make a difference,” he said. However, he acknowledged that the extra cost of the program is unclear. “We did not systematically collect data on cost,” he said, noting that the funding for the study paid for both the intervention and the analysis.

For now, he said, researchers are following the children in the study to see if they were able to access treatment services. Some of the investigators are also taking part in a randomized study to evaluate an intervention in children with social communication disorders, he said.

In an accompanying commentary, three pediatric specialists noted that the study is the first to analyze ASD screening in EI. “This study supports the notion of ASD screening as an iterative, multistep process that optimally involves multiple community stakeholders with varying levels of developmental expertise who have done the work to build trust with families,” write pediatrician Kate E. Wallis, MD, MPH, of Children’s Hospital of Philadelphia, graduate student Monica M. Abdul-Chani, MA, of the University of Alabama at Birmingham, and pediatrician Katharine E. Zuckerman, MD, MPH, of Oregon Health & Science University, Portland.

In regard to disparities in diagnosis in Spanish-speaking families, the commentary authors write that “locating a greater proportion of the ASD identification process in EI, which families are already familiar with, has no to low cost for families, and is likely geographically closer for families, can reduce structural barriers to identification.”

They add that the emphasis within Latino families on the “building of warm and caring relationships with others based on mutual trust and respect” can allow EI specialists to “develop relationships with families who may be afraid or skeptical of sharing what could be considered personal details of their family life.”

The commentary authors also note that “it remains all too common for language delays to be attributed to child exposure to two languages, even though data do not support this attribution. Bilingual EI staff can help to demystify this perpetual myth and better estimate a child’s communication and social skills in both languages as they communicate and play.”

The study was funded by grants from the Health Resources Services Administration and the National Institute of Mental Health. Dr. Sheldrick is cocreator of the Parent’s Observations of Social Interaction (POSI), which is one of the two first-stage screeners used in this study. He conducts research related to this instrument but receives no royalties. He reports grants from the National Institutes of Health. Coauthor Alice S. Carter, PhD, is cocreator of the POSI but receives no royalties. She is also cocreator of the Brief Infant Toddler Social Emotional Assessment, which is one of the two first-stage screeners used in this study, and receives royalties on the sale of the instrument. She reports grants from the National Institutes of Health and the Health Resources and Services Administration. Study coauthor Thomas I. Mackie, PhD, MPH, reports grants from the National Institute of Mental Health. Study coauthor Noah Hoch reports grants from the Health Resources Services Administration and the National Institute of Mental Health. No other disclosures from study authors are reported. Dr. Zuckerman reported grants from the National Institutes of Health and National Institute of Mental Health and consulting fees from H2N related to autism. The other commentary authors report no disclosures.

A new, augmented autism-screening strategy boosted the number of boys diagnosed with the condition, especially Spanish speakers, a new study finds. The research was published in JAMA Pediatrics

The number of diagnoses in girls didn’t budge significantly, however, surprising researchers. Still, the findings suggest that “multistage screening and appropriate access to diagnostic services can really move the needle on the early detection of autism and reducing disparities in autism diagnosis and detection,” said lead author R. Christopher Sheldrick, PhD, a Boston University research associate professor of health law, policy, and management, in an interview.

While early intervention is considered crucial, U.S. research suggests that several groups of children – the poor, racial and ethnic minorities, and non-English speakers – are more likely to be diagnosed with autism spectrum disorder (ASD) later in life. “They have much lower access to appropriate services, both to get kids diagnosed and to get the kinds of interventions that can be helpful for families,” Dr. Sheldrick said. “Our study is about trying to close the gap around diagnosis, the first step.”

For the new study, the researchers implemented an intervention strategy in Massachusetts at three Early Intervention (EI) programs, which provide autism screening to children who are referred by pediatricians or parents. The researchers then tracked the programs, all in Boston, and nine comparison programs from the greater Boston area from 2012 to 2018.

Overall, 33,326 children were assessed, all aged 14-36 months. Those at the intervention programs were chosen because they had high levels of poverty. Children at those programs were more likely to be Black than those at the comparison programs (30.7% vs. 12.2%), to be Spanish speakers (28.9% vs. 12.5%), and to be in the lowest household income bracket (66.9% vs. 54.2%). In both groups, about 64% of the children were male.

The intervention strategy aimed to reduce the reliance on screening tests. Instead, the study authors write, “our protocol emphasizes ASD screening as a process that includes clinician and parent decision-making.”

As Dr. Sheldrick explained, parents and specialists observe children together “and then decide whether it’s worth taking the next step, which is a full diagnostic assessment with a licensed professional.” According to the study, either the parent(s) or the specialists could make the referral for a full, university-based assessment.

The goal was to help specialists use their professional judgment more, he said, and refer children who don’t show signs of ASD via a screening instrument but still spark concern, he said. “We’re really trying to create a system in which the screening tools support professional judgment, but don’t really replace it.”

After weighting, the researchers found that diagnoses of ASD were more common in the intervention sites vs. comparison sites (incidence rate ratio, 1.6; 95% confidence interval, 1.3-2.1, P < .001), accounting for an extra 8.1 diagnoses per 1,000 per quarter. Among Spanish-speaking families only, diagnoses grew even more in the intervention sites vs. comparison sites (IRR, 2.6; 95% CI, 1.6-4.3; P < .001), representing 15.4 additional diagnoses per 1,000 children per quarter.

There was also an increase in diagnoses among boys in the intervention sites vs. comparison sites (IRR, 1.8; 95% CI, 1.4-2.3; P < .001), accounting for 14.8 additional diagnoses per 1,000 children per quarter. However, there was no statistically significant increase in diagnosis among girls (IRR, 1.1; 95% CI, 0.6-1.7; P = .84).

The finding about girls surprised the researchers. “The program was highly effective for boys, but really didn’t have any effect for girls,” Dr. Sheldrick said. “Even though autism is considered to be more common in boys, there are questions about whether it’s underidentified in girls. These data would be consistent with that view. So there’s work to do to be able to recognize how a young girl with autism might present and how you might note that in a sensitive way and then respond appropriately.”

The overall message of the study is “that screening with appropriate supports can make a difference,” he said. However, he acknowledged that the extra cost of the program is unclear. “We did not systematically collect data on cost,” he said, noting that the funding for the study paid for both the intervention and the analysis.

For now, he said, researchers are following the children in the study to see if they were able to access treatment services. Some of the investigators are also taking part in a randomized study to evaluate an intervention in children with social communication disorders, he said.

In an accompanying commentary, three pediatric specialists noted that the study is the first to analyze ASD screening in EI. “This study supports the notion of ASD screening as an iterative, multistep process that optimally involves multiple community stakeholders with varying levels of developmental expertise who have done the work to build trust with families,” write pediatrician Kate E. Wallis, MD, MPH, of Children’s Hospital of Philadelphia, graduate student Monica M. Abdul-Chani, MA, of the University of Alabama at Birmingham, and pediatrician Katharine E. Zuckerman, MD, MPH, of Oregon Health & Science University, Portland.

In regard to disparities in diagnosis in Spanish-speaking families, the commentary authors write that “locating a greater proportion of the ASD identification process in EI, which families are already familiar with, has no to low cost for families, and is likely geographically closer for families, can reduce structural barriers to identification.”

They add that the emphasis within Latino families on the “building of warm and caring relationships with others based on mutual trust and respect” can allow EI specialists to “develop relationships with families who may be afraid or skeptical of sharing what could be considered personal details of their family life.”

The commentary authors also note that “it remains all too common for language delays to be attributed to child exposure to two languages, even though data do not support this attribution. Bilingual EI staff can help to demystify this perpetual myth and better estimate a child’s communication and social skills in both languages as they communicate and play.”

The study was funded by grants from the Health Resources Services Administration and the National Institute of Mental Health. Dr. Sheldrick is cocreator of the Parent’s Observations of Social Interaction (POSI), which is one of the two first-stage screeners used in this study. He conducts research related to this instrument but receives no royalties. He reports grants from the National Institutes of Health. Coauthor Alice S. Carter, PhD, is cocreator of the POSI but receives no royalties. She is also cocreator of the Brief Infant Toddler Social Emotional Assessment, which is one of the two first-stage screeners used in this study, and receives royalties on the sale of the instrument. She reports grants from the National Institutes of Health and the Health Resources and Services Administration. Study coauthor Thomas I. Mackie, PhD, MPH, reports grants from the National Institute of Mental Health. Study coauthor Noah Hoch reports grants from the Health Resources Services Administration and the National Institute of Mental Health. No other disclosures from study authors are reported. Dr. Zuckerman reported grants from the National Institutes of Health and National Institute of Mental Health and consulting fees from H2N related to autism. The other commentary authors report no disclosures.

A new, augmented autism-screening strategy boosted the number of boys diagnosed with the condition, especially Spanish speakers, a new study finds. The research was published in JAMA Pediatrics

The number of diagnoses in girls didn’t budge significantly, however, surprising researchers. Still, the findings suggest that “multistage screening and appropriate access to diagnostic services can really move the needle on the early detection of autism and reducing disparities in autism diagnosis and detection,” said lead author R. Christopher Sheldrick, PhD, a Boston University research associate professor of health law, policy, and management, in an interview.

While early intervention is considered crucial, U.S. research suggests that several groups of children – the poor, racial and ethnic minorities, and non-English speakers – are more likely to be diagnosed with autism spectrum disorder (ASD) later in life. “They have much lower access to appropriate services, both to get kids diagnosed and to get the kinds of interventions that can be helpful for families,” Dr. Sheldrick said. “Our study is about trying to close the gap around diagnosis, the first step.”

For the new study, the researchers implemented an intervention strategy in Massachusetts at three Early Intervention (EI) programs, which provide autism screening to children who are referred by pediatricians or parents. The researchers then tracked the programs, all in Boston, and nine comparison programs from the greater Boston area from 2012 to 2018.

Overall, 33,326 children were assessed, all aged 14-36 months. Those at the intervention programs were chosen because they had high levels of poverty. Children at those programs were more likely to be Black than those at the comparison programs (30.7% vs. 12.2%), to be Spanish speakers (28.9% vs. 12.5%), and to be in the lowest household income bracket (66.9% vs. 54.2%). In both groups, about 64% of the children were male.

The intervention strategy aimed to reduce the reliance on screening tests. Instead, the study authors write, “our protocol emphasizes ASD screening as a process that includes clinician and parent decision-making.”

As Dr. Sheldrick explained, parents and specialists observe children together “and then decide whether it’s worth taking the next step, which is a full diagnostic assessment with a licensed professional.” According to the study, either the parent(s) or the specialists could make the referral for a full, university-based assessment.

The goal was to help specialists use their professional judgment more, he said, and refer children who don’t show signs of ASD via a screening instrument but still spark concern, he said. “We’re really trying to create a system in which the screening tools support professional judgment, but don’t really replace it.”

After weighting, the researchers found that diagnoses of ASD were more common in the intervention sites vs. comparison sites (incidence rate ratio, 1.6; 95% confidence interval, 1.3-2.1, P < .001), accounting for an extra 8.1 diagnoses per 1,000 per quarter. Among Spanish-speaking families only, diagnoses grew even more in the intervention sites vs. comparison sites (IRR, 2.6; 95% CI, 1.6-4.3; P < .001), representing 15.4 additional diagnoses per 1,000 children per quarter.

There was also an increase in diagnoses among boys in the intervention sites vs. comparison sites (IRR, 1.8; 95% CI, 1.4-2.3; P < .001), accounting for 14.8 additional diagnoses per 1,000 children per quarter. However, there was no statistically significant increase in diagnosis among girls (IRR, 1.1; 95% CI, 0.6-1.7; P = .84).

The finding about girls surprised the researchers. “The program was highly effective for boys, but really didn’t have any effect for girls,” Dr. Sheldrick said. “Even though autism is considered to be more common in boys, there are questions about whether it’s underidentified in girls. These data would be consistent with that view. So there’s work to do to be able to recognize how a young girl with autism might present and how you might note that in a sensitive way and then respond appropriately.”

The overall message of the study is “that screening with appropriate supports can make a difference,” he said. However, he acknowledged that the extra cost of the program is unclear. “We did not systematically collect data on cost,” he said, noting that the funding for the study paid for both the intervention and the analysis.

For now, he said, researchers are following the children in the study to see if they were able to access treatment services. Some of the investigators are also taking part in a randomized study to evaluate an intervention in children with social communication disorders, he said.

In an accompanying commentary, three pediatric specialists noted that the study is the first to analyze ASD screening in EI. “This study supports the notion of ASD screening as an iterative, multistep process that optimally involves multiple community stakeholders with varying levels of developmental expertise who have done the work to build trust with families,” write pediatrician Kate E. Wallis, MD, MPH, of Children’s Hospital of Philadelphia, graduate student Monica M. Abdul-Chani, MA, of the University of Alabama at Birmingham, and pediatrician Katharine E. Zuckerman, MD, MPH, of Oregon Health & Science University, Portland.

In regard to disparities in diagnosis in Spanish-speaking families, the commentary authors write that “locating a greater proportion of the ASD identification process in EI, which families are already familiar with, has no to low cost for families, and is likely geographically closer for families, can reduce structural barriers to identification.”

They add that the emphasis within Latino families on the “building of warm and caring relationships with others based on mutual trust and respect” can allow EI specialists to “develop relationships with families who may be afraid or skeptical of sharing what could be considered personal details of their family life.”

The commentary authors also note that “it remains all too common for language delays to be attributed to child exposure to two languages, even though data do not support this attribution. Bilingual EI staff can help to demystify this perpetual myth and better estimate a child’s communication and social skills in both languages as they communicate and play.”

The study was funded by grants from the Health Resources Services Administration and the National Institute of Mental Health. Dr. Sheldrick is cocreator of the Parent’s Observations of Social Interaction (POSI), which is one of the two first-stage screeners used in this study. He conducts research related to this instrument but receives no royalties. He reports grants from the National Institutes of Health. Coauthor Alice S. Carter, PhD, is cocreator of the POSI but receives no royalties. She is also cocreator of the Brief Infant Toddler Social Emotional Assessment, which is one of the two first-stage screeners used in this study, and receives royalties on the sale of the instrument. She reports grants from the National Institutes of Health and the Health Resources and Services Administration. Study coauthor Thomas I. Mackie, PhD, MPH, reports grants from the National Institute of Mental Health. Study coauthor Noah Hoch reports grants from the Health Resources Services Administration and the National Institute of Mental Health. No other disclosures from study authors are reported. Dr. Zuckerman reported grants from the National Institutes of Health and National Institute of Mental Health and consulting fees from H2N related to autism. The other commentary authors report no disclosures.

Mrs. S.’s long-term chronic obstructive pulmonary disease (COPD) prognosis was grim, and she faced a harder time getting through each day. But neither she nor her primary care physician was willing to embrace strategies other than drugs.

“She felt guilty for continuing to smoke, but also expressed a need to smoke to help her deal with her husband’s cancer and eventual death,” recalled Georgia Narsavage, PhD, RN, ANP-BC, professor emerita of nursing at West Virginia University. “Her primary care physician was reluctant to introduce any treatment other than medications because her family was resistant to facing ‘mother dying.’ ”

SDI Productions/E+

But things changed when Mrs. S. was referred to a palliative-care clinical nurse specialist following a hospitalization. “The goal of palliative care is to support quality of life by relieving symptoms and decreasing suffering. She was assisted to improve functioning overall, and home support services were provided,” Dr. Narsavage said. “They allowed her to live at home relatively pain free with decreased dyspnea for 3 more years until her transition to hospice care a few months before death.

It wasn’t quite a happy ending. But it was a happier ending, and one that palliative care (PC) advocates hope will become more common in pulmonary care. They’re working to convince colleagues that PC is neither another word for hospice nor a sign that anyone is giving up on a patient.
 

Underutilized but beneficial

“Palliative care is underutilized in patients with chronic pulmonary disease, and it’s a missed opportunity to potentially alleviate symptoms and improve quality of life,” said Hilary DuBrock, MD, an internist and critical care pulmonologist with the Mayo Clinic in Rochester, Minn. “Chest physicians should know that it’s important to recognize your limitations in addressing all aspects of a chronic disease, and it’s OK to ask for help from a specialty multidisciplinary team of palliative care providers.”

Statistics back up Dr. DuBrock’s perspective about how PC isn’t common in pulmonary care. A 2017 study examined 181,689 U.S. adult patients who had COPD, received oxygen at home, and were hospitalized for exacerbations from 2006-2012. Just 1.7% received PC, although the number grew over the study period.

Another study published in 2017 examined 3,166 patients over the same period with end-stage idiopathic pulmonary fibrosis (IPF) who were on ventilators. The use of PC is group rose from 2.3% in 2006 to 21.6% in 2012.

More recently, a 2020 meta-analysis examined 19 studies and found that patients with lung cancer were much more likely to receive PC than were those with COPD (odds ratio (OR) = 9.59, P < .001, for hospital-based PC and OR = 8.79, P < .001, for home-based PC).

Patients with lung cancer vs. COPD were also less likely to receive invasive ventilation (OR = .26, P < .001), noninvasive ventilation (OR = .63, P = .009) or CPR (OR = .29, P < .001) or die at a nursing home/long-term care facility (OR = .32, P < .001).

Other studies support PC in COPD: Research in Europe has linked PC in COPD to fewer in-hospital deaths and lower end-of-life expenses. A Canadian study also linked PC to fewer in-hospital deaths in COPD.

Dr. DuBrock said she believes there are a couple reasons why PC isn’t more widely accepted in pulmonology. “There has been little evidence in chronic pulmonary disease regarding the role of PC, and there is a lack of standardized guidelines to help clinicians determine appropriate timing and patient selection for referral,” she said. “There is also a reluctance to refer patients to palliative care since some may think that referral implies that they are giving up on their patients.”

In fact, she said, “if appropriately explained and discussed with patients, PC does not necessarily need to imply to patients that you are giving up on them, but rather that you care enough about them to try to find novel ways to improve their quality of life and relieve their symptoms. Additionally, palliative care can be provided alongside ongoing medical care and treatment of their chronic lung disease.”
 

More than standard care

Another obstacle comes from pulmonologists who claim PC isn’t necessary because they’re handling patient care themselves, said University of Alabama at Birmingham critical care pulmonologist Anand S. Iyer, MD. “They’ll say: ‘I do palliative care, I palliate their breathing. I treat breathlessness and cough, that’s what I do.’ ”

But these symptoms only brush the surface of patient needs, he said. “I don’t think that the average pulmonologist goes beyond that to comprehensive symptom assessment and management of a whole host of symptoms beyond those limited to the lungs – depression, anxiety, fatigue, malnutrition.”

On that latter front, he said, pulmonologists “are really good at having end-of-life conversations at the end of life. We do that every day in the ICU.” Advocates for PC, he said, “want to push that to the clinic a year or two earlier.”
 

Timing and use of PC

When should pulmonologists call in a PC team? Specialists recommend early consultations, even right after a pulmonary disease is diagnosed. “When a pulmonologist diagnoses a condition as a serious illness – especially chronic pulmonary disease – a consultation with a palliative care physician or advanced practice registered nurse” can help assess the need for care and the best time to introduce palliative care to the patient and family “to provide relief and enhance quality of life,” West Virginia University’s Dr. Narsavage said. “Initial diagnosis is not too early to think about the trajectory.

Dr. Iyer agreed that early PC consultation is key. “We’re talking about comprehensive support for the physical, emotional, and spiritual needs of patients and their families. It can grow as needs of patients become more severe.”

For her part, Dr. DuBrock urged colleagues to focus on patient experiences. “The exact timing of when to refer patients with pulmonary disease is not well established,” she said. “Thus, it’s important to take cues from our patients. If they are experiencing significant symptom burden or impaired quality of life or having difficulty coping with their lung disease, then it may be helpful to call in palliative care to address these issues alongside education and discussion with the patient about the role of palliative care to address their unmet needs.”

As an example, Dr. DuBrock spoke of one of her own patients who has pulmonary hypertension (PH), connective tissue disease, and interstitial lung disease. “Her hypertension was relatively well controlled, but she was still quite symptomatic as well as depressed and having difficulty sleeping. I struggled with wanting to help her feel better but I also recognized that more PH therapy wasn’t necessarily the answer,” Dr. Dubrock said. “After some discussions, I referred her to palliative care, and they were extremely helpful with addressing her symptoms with a combination of pharmacologic and nonpharmacologic therapy and also addressing some of her underlying concerns and fears regarding her prognosis and issues related to advance-care planning. Social work was also helpful with addressing some of her financial concerns. I continue to see her on regular basis and treat her PH, but her overall quality of life, sleep, and mood have improved substantially.”
 

First steps

According to specialists, the first step in the PC process with patients is to make sure they understand their conditions, their prognoses, and the role of palliative care itself.

Kathleen Oare Lindell, PhD, RN, associate professor of nursing at Medical University of South Carolina, Charleston, who specializes in PC in pulmonary disease, remembers taking the histories of patients with grim prognoses and “their look on their face was like, ‘I just have a common cold.’ ” In other cases, she said, patients may fear they’ll die immediately when they have 3-5 years to live.

Dr. Lindell, who has worked at a specialty center for patients with interstitial lung disease (ILD), emphasized the importance of speaking in layperson terms that patients understand, such as referring to idiopathic pulmonary fibrosis as “unknown lung scarring.” She also said it’s crucial to be up front about their prognoses.

As for patient understanding of PC, she said, “people think it’s hospice that they’re giving. Palliative care is neither. Instead, it helps to address symptom management, I always tell patients, ‘You’ll be scared, you’ll have a cough. There are medicines and nonpharmacological therapies [that can help], and that’s what palliative care does.’ ”

Keith Swetz, MD, an internist and palliative care specialist at the University of Alabama at Birmingham, agreed that a concise discussion of prognosis is vital. “What do they know about their illness, and what do they understand about what will happen when things get worse?” he said.

“With pulmonary disease, they may be looking at months to years punctuated with a lot of ICU admissions, trips to the hospital, symptom burden, and decline in function. Some will want aggressive treatment and say they’re fine being in the hospital, while others will say being comfortable at home is more important.”

Dr. Swetz’s patients commonly have COPD, interstitial lung disease, pulmonary fibrosis, or PH, and some may have concurrent heart failure. While their prognoses may be poor, he said, discussion about their wishes probably aren’t happening outside of the PC setting.

Or if they are happening, he said, they’re lower quality, boiling down complicated care questions to “Do you want us to do everything yes, or no?

“A lot of it has to do with time,” he said. “Clinicians are busy, they might have a full ICU or pulmonary clinic with 15 minutes to see patients. Sitting down and talking about these things isn’t something that’s prioritized or fits into the work stream very well, and often it hasn’t been reimbursed.”

There typically aren’t insurance hassles regarding referrals for PC, Dr. Iyer said, although finding available specialists may be challenging. A 2019 study projected a wave of retirements of older PC physicians over the next few years, and the ratio of patients to PC specialists may not return to 2019 levels for decades. Rural areas are especially shorthanded. But telehealth may improve access, Dr. Iyer said.

What’s next? Specialists are trying to pin down guidelines for when PC consultation is appropriate in pulmonary disease.
 

Triggers to PC

Dr. Iyer, Dr. Lindell and others authored a 2021 report in the journal CHEST that offers guidance about triggers for PC consultation. The authors cited four “levers” or triggers that are important: worsening lung function, severe symptoms or high burden of care needs, poor prognosis, and frequent severe exacerbations.

“The overall point here is that integrating palliative care into COPD practice isn’t an on-off switch; rather, it should be based upon multiple factors and can evolve over time,” they wrote.

They noted that, “patients with COPD accept palliative care as early as moderate COPD (FEV₁ < 80%), so patients may be ready sooner than clinicians think.”

They added that, “if prognosis is such a concern that a clinician is considering referral for lung transplant evaluation, then concurrent referral to specialist palliative care should be routine practice.

Finally, frequent severe exacerbations, i.e. those that require hospitalization or an emergency room visit, carry a high risk for posthospitalization mortality and are ideal inflection points in the illness trajectory of COPD.”

In the big picture, the authors contend, “palliative care should be integrated early and concurrently with COPD-directed therapies, and its intensity should increase over time as symptoms, needs, and exacerbations worsen approaching EOL [end of life].”

None of the interviewees or other authors reported having any relevant conflicts for this story.

Mrs. S.’s long-term chronic obstructive pulmonary disease (COPD) prognosis was grim, and she faced a harder time getting through each day. But neither she nor her primary care physician was willing to embrace strategies other than drugs.

“She felt guilty for continuing to smoke, but also expressed a need to smoke to help her deal with her husband’s cancer and eventual death,” recalled Georgia Narsavage, PhD, RN, ANP-BC, professor emerita of nursing at West Virginia University. “Her primary care physician was reluctant to introduce any treatment other than medications because her family was resistant to facing ‘mother dying.’ ”

SDI Productions/E+

But things changed when Mrs. S. was referred to a palliative-care clinical nurse specialist following a hospitalization. “The goal of palliative care is to support quality of life by relieving symptoms and decreasing suffering. She was assisted to improve functioning overall, and home support services were provided,” Dr. Narsavage said. “They allowed her to live at home relatively pain free with decreased dyspnea for 3 more years until her transition to hospice care a few months before death.

It wasn’t quite a happy ending. But it was a happier ending, and one that palliative care (PC) advocates hope will become more common in pulmonary care. They’re working to convince colleagues that PC is neither another word for hospice nor a sign that anyone is giving up on a patient.
 

Underutilized but beneficial

“Palliative care is underutilized in patients with chronic pulmonary disease, and it’s a missed opportunity to potentially alleviate symptoms and improve quality of life,” said Hilary DuBrock, MD, an internist and critical care pulmonologist with the Mayo Clinic in Rochester, Minn. “Chest physicians should know that it’s important to recognize your limitations in addressing all aspects of a chronic disease, and it’s OK to ask for help from a specialty multidisciplinary team of palliative care providers.”

Statistics back up Dr. DuBrock’s perspective about how PC isn’t common in pulmonary care. A 2017 study examined 181,689 U.S. adult patients who had COPD, received oxygen at home, and were hospitalized for exacerbations from 2006-2012. Just 1.7% received PC, although the number grew over the study period.

Another study published in 2017 examined 3,166 patients over the same period with end-stage idiopathic pulmonary fibrosis (IPF) who were on ventilators. The use of PC is group rose from 2.3% in 2006 to 21.6% in 2012.

More recently, a 2020 meta-analysis examined 19 studies and found that patients with lung cancer were much more likely to receive PC than were those with COPD (odds ratio (OR) = 9.59, P < .001, for hospital-based PC and OR = 8.79, P < .001, for home-based PC).

Patients with lung cancer vs. COPD were also less likely to receive invasive ventilation (OR = .26, P < .001), noninvasive ventilation (OR = .63, P = .009) or CPR (OR = .29, P < .001) or die at a nursing home/long-term care facility (OR = .32, P < .001).

Other studies support PC in COPD: Research in Europe has linked PC in COPD to fewer in-hospital deaths and lower end-of-life expenses. A Canadian study also linked PC to fewer in-hospital deaths in COPD.

Dr. DuBrock said she believes there are a couple reasons why PC isn’t more widely accepted in pulmonology. “There has been little evidence in chronic pulmonary disease regarding the role of PC, and there is a lack of standardized guidelines to help clinicians determine appropriate timing and patient selection for referral,” she said. “There is also a reluctance to refer patients to palliative care since some may think that referral implies that they are giving up on their patients.”

In fact, she said, “if appropriately explained and discussed with patients, PC does not necessarily need to imply to patients that you are giving up on them, but rather that you care enough about them to try to find novel ways to improve their quality of life and relieve their symptoms. Additionally, palliative care can be provided alongside ongoing medical care and treatment of their chronic lung disease.”
 

More than standard care

Another obstacle comes from pulmonologists who claim PC isn’t necessary because they’re handling patient care themselves, said University of Alabama at Birmingham critical care pulmonologist Anand S. Iyer, MD. “They’ll say: ‘I do palliative care, I palliate their breathing. I treat breathlessness and cough, that’s what I do.’ ”

But these symptoms only brush the surface of patient needs, he said. “I don’t think that the average pulmonologist goes beyond that to comprehensive symptom assessment and management of a whole host of symptoms beyond those limited to the lungs – depression, anxiety, fatigue, malnutrition.”

On that latter front, he said, pulmonologists “are really good at having end-of-life conversations at the end of life. We do that every day in the ICU.” Advocates for PC, he said, “want to push that to the clinic a year or two earlier.”
 

Timing and use of PC

When should pulmonologists call in a PC team? Specialists recommend early consultations, even right after a pulmonary disease is diagnosed. “When a pulmonologist diagnoses a condition as a serious illness – especially chronic pulmonary disease – a consultation with a palliative care physician or advanced practice registered nurse” can help assess the need for care and the best time to introduce palliative care to the patient and family “to provide relief and enhance quality of life,” West Virginia University’s Dr. Narsavage said. “Initial diagnosis is not too early to think about the trajectory.

Dr. Iyer agreed that early PC consultation is key. “We’re talking about comprehensive support for the physical, emotional, and spiritual needs of patients and their families. It can grow as needs of patients become more severe.”

For her part, Dr. DuBrock urged colleagues to focus on patient experiences. “The exact timing of when to refer patients with pulmonary disease is not well established,” she said. “Thus, it’s important to take cues from our patients. If they are experiencing significant symptom burden or impaired quality of life or having difficulty coping with their lung disease, then it may be helpful to call in palliative care to address these issues alongside education and discussion with the patient about the role of palliative care to address their unmet needs.”

As an example, Dr. DuBrock spoke of one of her own patients who has pulmonary hypertension (PH), connective tissue disease, and interstitial lung disease. “Her hypertension was relatively well controlled, but she was still quite symptomatic as well as depressed and having difficulty sleeping. I struggled with wanting to help her feel better but I also recognized that more PH therapy wasn’t necessarily the answer,” Dr. Dubrock said. “After some discussions, I referred her to palliative care, and they were extremely helpful with addressing her symptoms with a combination of pharmacologic and nonpharmacologic therapy and also addressing some of her underlying concerns and fears regarding her prognosis and issues related to advance-care planning. Social work was also helpful with addressing some of her financial concerns. I continue to see her on regular basis and treat her PH, but her overall quality of life, sleep, and mood have improved substantially.”
 

First steps

According to specialists, the first step in the PC process with patients is to make sure they understand their conditions, their prognoses, and the role of palliative care itself.

Kathleen Oare Lindell, PhD, RN, associate professor of nursing at Medical University of South Carolina, Charleston, who specializes in PC in pulmonary disease, remembers taking the histories of patients with grim prognoses and “their look on their face was like, ‘I just have a common cold.’ ” In other cases, she said, patients may fear they’ll die immediately when they have 3-5 years to live.

Dr. Lindell, who has worked at a specialty center for patients with interstitial lung disease (ILD), emphasized the importance of speaking in layperson terms that patients understand, such as referring to idiopathic pulmonary fibrosis as “unknown lung scarring.” She also said it’s crucial to be up front about their prognoses.

As for patient understanding of PC, she said, “people think it’s hospice that they’re giving. Palliative care is neither. Instead, it helps to address symptom management, I always tell patients, ‘You’ll be scared, you’ll have a cough. There are medicines and nonpharmacological therapies [that can help], and that’s what palliative care does.’ ”

Keith Swetz, MD, an internist and palliative care specialist at the University of Alabama at Birmingham, agreed that a concise discussion of prognosis is vital. “What do they know about their illness, and what do they understand about what will happen when things get worse?” he said.

“With pulmonary disease, they may be looking at months to years punctuated with a lot of ICU admissions, trips to the hospital, symptom burden, and decline in function. Some will want aggressive treatment and say they’re fine being in the hospital, while others will say being comfortable at home is more important.”

Dr. Swetz’s patients commonly have COPD, interstitial lung disease, pulmonary fibrosis, or PH, and some may have concurrent heart failure. While their prognoses may be poor, he said, discussion about their wishes probably aren’t happening outside of the PC setting.

Or if they are happening, he said, they’re lower quality, boiling down complicated care questions to “Do you want us to do everything yes, or no?

“A lot of it has to do with time,” he said. “Clinicians are busy, they might have a full ICU or pulmonary clinic with 15 minutes to see patients. Sitting down and talking about these things isn’t something that’s prioritized or fits into the work stream very well, and often it hasn’t been reimbursed.”

There typically aren’t insurance hassles regarding referrals for PC, Dr. Iyer said, although finding available specialists may be challenging. A 2019 study projected a wave of retirements of older PC physicians over the next few years, and the ratio of patients to PC specialists may not return to 2019 levels for decades. Rural areas are especially shorthanded. But telehealth may improve access, Dr. Iyer said.

What’s next? Specialists are trying to pin down guidelines for when PC consultation is appropriate in pulmonary disease.
 

Triggers to PC

Dr. Iyer, Dr. Lindell and others authored a 2021 report in the journal CHEST that offers guidance about triggers for PC consultation. The authors cited four “levers” or triggers that are important: worsening lung function, severe symptoms or high burden of care needs, poor prognosis, and frequent severe exacerbations.

“The overall point here is that integrating palliative care into COPD practice isn’t an on-off switch; rather, it should be based upon multiple factors and can evolve over time,” they wrote.

They noted that, “patients with COPD accept palliative care as early as moderate COPD (FEV₁ < 80%), so patients may be ready sooner than clinicians think.”

They added that, “if prognosis is such a concern that a clinician is considering referral for lung transplant evaluation, then concurrent referral to specialist palliative care should be routine practice.

Finally, frequent severe exacerbations, i.e. those that require hospitalization or an emergency room visit, carry a high risk for posthospitalization mortality and are ideal inflection points in the illness trajectory of COPD.”

In the big picture, the authors contend, “palliative care should be integrated early and concurrently with COPD-directed therapies, and its intensity should increase over time as symptoms, needs, and exacerbations worsen approaching EOL [end of life].”

None of the interviewees or other authors reported having any relevant conflicts for this story.

Mrs. S.’s long-term chronic obstructive pulmonary disease (COPD) prognosis was grim, and she faced a harder time getting through each day. But neither she nor her primary care physician was willing to embrace strategies other than drugs.

“She felt guilty for continuing to smoke, but also expressed a need to smoke to help her deal with her husband’s cancer and eventual death,” recalled Georgia Narsavage, PhD, RN, ANP-BC, professor emerita of nursing at West Virginia University. “Her primary care physician was reluctant to introduce any treatment other than medications because her family was resistant to facing ‘mother dying.’ ”

SDI Productions/E+

But things changed when Mrs. S. was referred to a palliative-care clinical nurse specialist following a hospitalization. “The goal of palliative care is to support quality of life by relieving symptoms and decreasing suffering. She was assisted to improve functioning overall, and home support services were provided,” Dr. Narsavage said. “They allowed her to live at home relatively pain free with decreased dyspnea for 3 more years until her transition to hospice care a few months before death.

It wasn’t quite a happy ending. But it was a happier ending, and one that palliative care (PC) advocates hope will become more common in pulmonary care. They’re working to convince colleagues that PC is neither another word for hospice nor a sign that anyone is giving up on a patient.
 

Underutilized but beneficial

“Palliative care is underutilized in patients with chronic pulmonary disease, and it’s a missed opportunity to potentially alleviate symptoms and improve quality of life,” said Hilary DuBrock, MD, an internist and critical care pulmonologist with the Mayo Clinic in Rochester, Minn. “Chest physicians should know that it’s important to recognize your limitations in addressing all aspects of a chronic disease, and it’s OK to ask for help from a specialty multidisciplinary team of palliative care providers.”

Statistics back up Dr. DuBrock’s perspective about how PC isn’t common in pulmonary care. A 2017 study examined 181,689 U.S. adult patients who had COPD, received oxygen at home, and were hospitalized for exacerbations from 2006-2012. Just 1.7% received PC, although the number grew over the study period.

Another study published in 2017 examined 3,166 patients over the same period with end-stage idiopathic pulmonary fibrosis (IPF) who were on ventilators. The use of PC is group rose from 2.3% in 2006 to 21.6% in 2012.

More recently, a 2020 meta-analysis examined 19 studies and found that patients with lung cancer were much more likely to receive PC than were those with COPD (odds ratio (OR) = 9.59, P < .001, for hospital-based PC and OR = 8.79, P < .001, for home-based PC).

Patients with lung cancer vs. COPD were also less likely to receive invasive ventilation (OR = .26, P < .001), noninvasive ventilation (OR = .63, P = .009) or CPR (OR = .29, P < .001) or die at a nursing home/long-term care facility (OR = .32, P < .001).

Other studies support PC in COPD: Research in Europe has linked PC in COPD to fewer in-hospital deaths and lower end-of-life expenses. A Canadian study also linked PC to fewer in-hospital deaths in COPD.

Dr. DuBrock said she believes there are a couple reasons why PC isn’t more widely accepted in pulmonology. “There has been little evidence in chronic pulmonary disease regarding the role of PC, and there is a lack of standardized guidelines to help clinicians determine appropriate timing and patient selection for referral,” she said. “There is also a reluctance to refer patients to palliative care since some may think that referral implies that they are giving up on their patients.”

In fact, she said, “if appropriately explained and discussed with patients, PC does not necessarily need to imply to patients that you are giving up on them, but rather that you care enough about them to try to find novel ways to improve their quality of life and relieve their symptoms. Additionally, palliative care can be provided alongside ongoing medical care and treatment of their chronic lung disease.”
 

More than standard care

Another obstacle comes from pulmonologists who claim PC isn’t necessary because they’re handling patient care themselves, said University of Alabama at Birmingham critical care pulmonologist Anand S. Iyer, MD. “They’ll say: ‘I do palliative care, I palliate their breathing. I treat breathlessness and cough, that’s what I do.’ ”

But these symptoms only brush the surface of patient needs, he said. “I don’t think that the average pulmonologist goes beyond that to comprehensive symptom assessment and management of a whole host of symptoms beyond those limited to the lungs – depression, anxiety, fatigue, malnutrition.”

On that latter front, he said, pulmonologists “are really good at having end-of-life conversations at the end of life. We do that every day in the ICU.” Advocates for PC, he said, “want to push that to the clinic a year or two earlier.”
 

Timing and use of PC

When should pulmonologists call in a PC team? Specialists recommend early consultations, even right after a pulmonary disease is diagnosed. “When a pulmonologist diagnoses a condition as a serious illness – especially chronic pulmonary disease – a consultation with a palliative care physician or advanced practice registered nurse” can help assess the need for care and the best time to introduce palliative care to the patient and family “to provide relief and enhance quality of life,” West Virginia University’s Dr. Narsavage said. “Initial diagnosis is not too early to think about the trajectory.

Dr. Iyer agreed that early PC consultation is key. “We’re talking about comprehensive support for the physical, emotional, and spiritual needs of patients and their families. It can grow as needs of patients become more severe.”

For her part, Dr. DuBrock urged colleagues to focus on patient experiences. “The exact timing of when to refer patients with pulmonary disease is not well established,” she said. “Thus, it’s important to take cues from our patients. If they are experiencing significant symptom burden or impaired quality of life or having difficulty coping with their lung disease, then it may be helpful to call in palliative care to address these issues alongside education and discussion with the patient about the role of palliative care to address their unmet needs.”

As an example, Dr. DuBrock spoke of one of her own patients who has pulmonary hypertension (PH), connective tissue disease, and interstitial lung disease. “Her hypertension was relatively well controlled, but she was still quite symptomatic as well as depressed and having difficulty sleeping. I struggled with wanting to help her feel better but I also recognized that more PH therapy wasn’t necessarily the answer,” Dr. Dubrock said. “After some discussions, I referred her to palliative care, and they were extremely helpful with addressing her symptoms with a combination of pharmacologic and nonpharmacologic therapy and also addressing some of her underlying concerns and fears regarding her prognosis and issues related to advance-care planning. Social work was also helpful with addressing some of her financial concerns. I continue to see her on regular basis and treat her PH, but her overall quality of life, sleep, and mood have improved substantially.”
 

First steps

According to specialists, the first step in the PC process with patients is to make sure they understand their conditions, their prognoses, and the role of palliative care itself.

Kathleen Oare Lindell, PhD, RN, associate professor of nursing at Medical University of South Carolina, Charleston, who specializes in PC in pulmonary disease, remembers taking the histories of patients with grim prognoses and “their look on their face was like, ‘I just have a common cold.’ ” In other cases, she said, patients may fear they’ll die immediately when they have 3-5 years to live.

Dr. Lindell, who has worked at a specialty center for patients with interstitial lung disease (ILD), emphasized the importance of speaking in layperson terms that patients understand, such as referring to idiopathic pulmonary fibrosis as “unknown lung scarring.” She also said it’s crucial to be up front about their prognoses.

As for patient understanding of PC, she said, “people think it’s hospice that they’re giving. Palliative care is neither. Instead, it helps to address symptom management, I always tell patients, ‘You’ll be scared, you’ll have a cough. There are medicines and nonpharmacological therapies [that can help], and that’s what palliative care does.’ ”

Keith Swetz, MD, an internist and palliative care specialist at the University of Alabama at Birmingham, agreed that a concise discussion of prognosis is vital. “What do they know about their illness, and what do they understand about what will happen when things get worse?” he said.

“With pulmonary disease, they may be looking at months to years punctuated with a lot of ICU admissions, trips to the hospital, symptom burden, and decline in function. Some will want aggressive treatment and say they’re fine being in the hospital, while others will say being comfortable at home is more important.”

Dr. Swetz’s patients commonly have COPD, interstitial lung disease, pulmonary fibrosis, or PH, and some may have concurrent heart failure. While their prognoses may be poor, he said, discussion about their wishes probably aren’t happening outside of the PC setting.

Or if they are happening, he said, they’re lower quality, boiling down complicated care questions to “Do you want us to do everything yes, or no?

“A lot of it has to do with time,” he said. “Clinicians are busy, they might have a full ICU or pulmonary clinic with 15 minutes to see patients. Sitting down and talking about these things isn’t something that’s prioritized or fits into the work stream very well, and often it hasn’t been reimbursed.”

There typically aren’t insurance hassles regarding referrals for PC, Dr. Iyer said, although finding available specialists may be challenging. A 2019 study projected a wave of retirements of older PC physicians over the next few years, and the ratio of patients to PC specialists may not return to 2019 levels for decades. Rural areas are especially shorthanded. But telehealth may improve access, Dr. Iyer said.

What’s next? Specialists are trying to pin down guidelines for when PC consultation is appropriate in pulmonary disease.
 

Triggers to PC

Dr. Iyer, Dr. Lindell and others authored a 2021 report in the journal CHEST that offers guidance about triggers for PC consultation. The authors cited four “levers” or triggers that are important: worsening lung function, severe symptoms or high burden of care needs, poor prognosis, and frequent severe exacerbations.

“The overall point here is that integrating palliative care into COPD practice isn’t an on-off switch; rather, it should be based upon multiple factors and can evolve over time,” they wrote.

They noted that, “patients with COPD accept palliative care as early as moderate COPD (FEV₁ < 80%), so patients may be ready sooner than clinicians think.”

They added that, “if prognosis is such a concern that a clinician is considering referral for lung transplant evaluation, then concurrent referral to specialist palliative care should be routine practice.

Finally, frequent severe exacerbations, i.e. those that require hospitalization or an emergency room visit, carry a high risk for posthospitalization mortality and are ideal inflection points in the illness trajectory of COPD.”

In the big picture, the authors contend, “palliative care should be integrated early and concurrently with COPD-directed therapies, and its intensity should increase over time as symptoms, needs, and exacerbations worsen approaching EOL [end of life].”

None of the interviewees or other authors reported having any relevant conflicts for this story.

New research offers more insight into potentially dangerous racial disparities in cesarean deliveries: In first-time live births, healthy African-American and Hispanic mothers were 21% and 26% more likely than White mothers, respectively, to deliver by cesarean section despite being low risk. The higher number of cesareans appeared to boost their risk of morbidity.

“A 20% increased odds of cesarean among otherwise healthy, low-risk, nulliparous individuals at term – with limited medical or obstetric explanation – is a significant concern, especially when considering that cesarean is the most common surgical procedure in the U.S.,” said study author Michelle P. Debbink, MD, PhD, an assistant professor with the department of obstetrics and gynecology at the University of Utah, in an interview.

Dr. Debbink and colleagues launched the study, published in the Jan. 2022 issue of Obstetrics & Gynecology, to better understand the racial gap in cesarean sections, which are considered riskier than vaginal deliveries. “Several studies have shown that Black women undergo cesarean more frequently than non-Hispanic White women. Numerous studies also show that Hispanic/Latina women undergo cesarean more frequently than White women, although these data are a bit more mixed,” she said. “What we don’t know, however, is why these differences occur and whether there are clues in the data which can point us toward interventions to close the gap.”

One theory, she said, is that Black and Hispanic women have more comorbidities and therefore more cesareans. To test that idea, the researchers found a cohort of healthy women in a randomized trial that studied the induction of labor.

For the study, they focused on 5,759 women (24.3% Black, 30% Hispanic, 46.6% White). Major differences between the groups included maternal age (average = 21 for Black, 22 for Hispanic, and 26 for White, P < .001), private insurance (17% for Black and Hispanic, 75% for White; P < .001), and full or part-time employment (37% for Black, 31% for Hispanic, and 71% for White; P < .001).

A total of 1,158 of the women (20.1%) underwent cesarean deliveries, accounting for 23% of deliveries by Black women, 22.8% of those by Hispanic women, and 17.6% of those by White women (P < .001). Black women were 21% more likely than White women to give birth via cesarean (adjusted relative risk = 1.21, 95% CI: 1.03-1.42) and Hispanic women were 26% more likely (aRR = 1.26, 95% CI: 1.08-1.46).

The study doesn’t explore why Black and Hispanic women have more cesarean deliveries. However, Dr. Debbink said, “we hypothesize that the difference likely stems more from differing treatment of Black or Hispanic individuals during labor.” It’s unlikely, she said, that these women are more likely to prefer cesarean sections. For one thing, she said, other research hasn’t shown a difference in preferences by race.

The researchers also analyzed maternal morbidity, defined as “transfusion of 4 or more units of red blood cells, any transfusion of other products, postpartum infection, intensive care unit admission, hysterectomy, venous thromboembolism, or maternal death.”

The study found that while few women (2.3%) suffered from morbidity, Black (aRR = 2.05, 95% CI: 1.21-3.47) and Hispanic (aRR = 1.92, 95% CI: 1.17-3.14) women were more likely to suffer from it than White women.

The researchers report that “cesarean birth accounted for an estimated 15.8% (95% CI: 2.1%-48.7%) and 16.5% (95% CI: 4.0%-44.0%) of excess maternal morbidity among non-Hispanic Black and Hispanic people, respectively.”

“Both endometritis and wound complications are much more common among individuals with cesarean, and blood clots, hysterectomy, and ICU admission are also more common after cesarean compared with vaginal delivery,” Dr. Debbink said.

The message of the study, she said, is that the health care system “perpetuates gaps in cesarean delivery for Black and Hispanic individuals compared to White individuals” even in low-risk, first-time live births. “We do not yet know exactly what the right levers are to address this gap, but it is important that we ob-gyns examine our practice patterns and our hospitals’ practice patterns to ensure equity for all our patients.”

Rebecca Delafield, PhD, an assistant professor of Native Hawaiian Health at the University of Hawaii, praised the study as “well-conducted” in an interview. “I agree with the assessment that while the cesarean delivery accounts for a modest proportion of excess morbidity in this study, the impact at the population level is significant,” said Dr. Delafield, who studies health disparities and didn’t take part in the study. “Delivery is complex and the causes of disparities observed are likely multifactorial, therefore research such as this is necessary and compelling.”

She added: “It is becoming increasingly evident that studies investigating racial/ethnic disparities in cesarean delivery and other maternal health outcomes must look beyond maternal behavioral or medical risk factors – e.g., obesity or hypertension – and consider the contribution of a broader set of factors, including societal prejudices.”

The study is funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Advancing Translational Sciences. One study author reports funding from GlaxoSmithKline, Pfizer, Moderna, and UpToDate (contributor) and from the Centers for Disease Control and Prevention (via her institution). Dr. Debbink, the other authors, and Dr. Delafield report no disclosures.

New research offers more insight into potentially dangerous racial disparities in cesarean deliveries: In first-time live births, healthy African-American and Hispanic mothers were 21% and 26% more likely than White mothers, respectively, to deliver by cesarean section despite being low risk. The higher number of cesareans appeared to boost their risk of morbidity.

“A 20% increased odds of cesarean among otherwise healthy, low-risk, nulliparous individuals at term – with limited medical or obstetric explanation – is a significant concern, especially when considering that cesarean is the most common surgical procedure in the U.S.,” said study author Michelle P. Debbink, MD, PhD, an assistant professor with the department of obstetrics and gynecology at the University of Utah, in an interview.

Dr. Debbink and colleagues launched the study, published in the Jan. 2022 issue of Obstetrics & Gynecology, to better understand the racial gap in cesarean sections, which are considered riskier than vaginal deliveries. “Several studies have shown that Black women undergo cesarean more frequently than non-Hispanic White women. Numerous studies also show that Hispanic/Latina women undergo cesarean more frequently than White women, although these data are a bit more mixed,” she said. “What we don’t know, however, is why these differences occur and whether there are clues in the data which can point us toward interventions to close the gap.”

One theory, she said, is that Black and Hispanic women have more comorbidities and therefore more cesareans. To test that idea, the researchers found a cohort of healthy women in a randomized trial that studied the induction of labor.

For the study, they focused on 5,759 women (24.3% Black, 30% Hispanic, 46.6% White). Major differences between the groups included maternal age (average = 21 for Black, 22 for Hispanic, and 26 for White, P < .001), private insurance (17% for Black and Hispanic, 75% for White; P < .001), and full or part-time employment (37% for Black, 31% for Hispanic, and 71% for White; P < .001).

A total of 1,158 of the women (20.1%) underwent cesarean deliveries, accounting for 23% of deliveries by Black women, 22.8% of those by Hispanic women, and 17.6% of those by White women (P < .001). Black women were 21% more likely than White women to give birth via cesarean (adjusted relative risk = 1.21, 95% CI: 1.03-1.42) and Hispanic women were 26% more likely (aRR = 1.26, 95% CI: 1.08-1.46).

The study doesn’t explore why Black and Hispanic women have more cesarean deliveries. However, Dr. Debbink said, “we hypothesize that the difference likely stems more from differing treatment of Black or Hispanic individuals during labor.” It’s unlikely, she said, that these women are more likely to prefer cesarean sections. For one thing, she said, other research hasn’t shown a difference in preferences by race.

The researchers also analyzed maternal morbidity, defined as “transfusion of 4 or more units of red blood cells, any transfusion of other products, postpartum infection, intensive care unit admission, hysterectomy, venous thromboembolism, or maternal death.”

The study found that while few women (2.3%) suffered from morbidity, Black (aRR = 2.05, 95% CI: 1.21-3.47) and Hispanic (aRR = 1.92, 95% CI: 1.17-3.14) women were more likely to suffer from it than White women.

The researchers report that “cesarean birth accounted for an estimated 15.8% (95% CI: 2.1%-48.7%) and 16.5% (95% CI: 4.0%-44.0%) of excess maternal morbidity among non-Hispanic Black and Hispanic people, respectively.”

“Both endometritis and wound complications are much more common among individuals with cesarean, and blood clots, hysterectomy, and ICU admission are also more common after cesarean compared with vaginal delivery,” Dr. Debbink said.

The message of the study, she said, is that the health care system “perpetuates gaps in cesarean delivery for Black and Hispanic individuals compared to White individuals” even in low-risk, first-time live births. “We do not yet know exactly what the right levers are to address this gap, but it is important that we ob-gyns examine our practice patterns and our hospitals’ practice patterns to ensure equity for all our patients.”

Rebecca Delafield, PhD, an assistant professor of Native Hawaiian Health at the University of Hawaii, praised the study as “well-conducted” in an interview. “I agree with the assessment that while the cesarean delivery accounts for a modest proportion of excess morbidity in this study, the impact at the population level is significant,” said Dr. Delafield, who studies health disparities and didn’t take part in the study. “Delivery is complex and the causes of disparities observed are likely multifactorial, therefore research such as this is necessary and compelling.”

She added: “It is becoming increasingly evident that studies investigating racial/ethnic disparities in cesarean delivery and other maternal health outcomes must look beyond maternal behavioral or medical risk factors – e.g., obesity or hypertension – and consider the contribution of a broader set of factors, including societal prejudices.”

The study is funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Advancing Translational Sciences. One study author reports funding from GlaxoSmithKline, Pfizer, Moderna, and UpToDate (contributor) and from the Centers for Disease Control and Prevention (via her institution). Dr. Debbink, the other authors, and Dr. Delafield report no disclosures.

New research offers more insight into potentially dangerous racial disparities in cesarean deliveries: In first-time live births, healthy African-American and Hispanic mothers were 21% and 26% more likely than White mothers, respectively, to deliver by cesarean section despite being low risk. The higher number of cesareans appeared to boost their risk of morbidity.

“A 20% increased odds of cesarean among otherwise healthy, low-risk, nulliparous individuals at term – with limited medical or obstetric explanation – is a significant concern, especially when considering that cesarean is the most common surgical procedure in the U.S.,” said study author Michelle P. Debbink, MD, PhD, an assistant professor with the department of obstetrics and gynecology at the University of Utah, in an interview.

Dr. Debbink and colleagues launched the study, published in the Jan. 2022 issue of Obstetrics & Gynecology, to better understand the racial gap in cesarean sections, which are considered riskier than vaginal deliveries. “Several studies have shown that Black women undergo cesarean more frequently than non-Hispanic White women. Numerous studies also show that Hispanic/Latina women undergo cesarean more frequently than White women, although these data are a bit more mixed,” she said. “What we don’t know, however, is why these differences occur and whether there are clues in the data which can point us toward interventions to close the gap.”

One theory, she said, is that Black and Hispanic women have more comorbidities and therefore more cesareans. To test that idea, the researchers found a cohort of healthy women in a randomized trial that studied the induction of labor.

For the study, they focused on 5,759 women (24.3% Black, 30% Hispanic, 46.6% White). Major differences between the groups included maternal age (average = 21 for Black, 22 for Hispanic, and 26 for White, P < .001), private insurance (17% for Black and Hispanic, 75% for White; P < .001), and full or part-time employment (37% for Black, 31% for Hispanic, and 71% for White; P < .001).

A total of 1,158 of the women (20.1%) underwent cesarean deliveries, accounting for 23% of deliveries by Black women, 22.8% of those by Hispanic women, and 17.6% of those by White women (P < .001). Black women were 21% more likely than White women to give birth via cesarean (adjusted relative risk = 1.21, 95% CI: 1.03-1.42) and Hispanic women were 26% more likely (aRR = 1.26, 95% CI: 1.08-1.46).

The study doesn’t explore why Black and Hispanic women have more cesarean deliveries. However, Dr. Debbink said, “we hypothesize that the difference likely stems more from differing treatment of Black or Hispanic individuals during labor.” It’s unlikely, she said, that these women are more likely to prefer cesarean sections. For one thing, she said, other research hasn’t shown a difference in preferences by race.

The researchers also analyzed maternal morbidity, defined as “transfusion of 4 or more units of red blood cells, any transfusion of other products, postpartum infection, intensive care unit admission, hysterectomy, venous thromboembolism, or maternal death.”

The study found that while few women (2.3%) suffered from morbidity, Black (aRR = 2.05, 95% CI: 1.21-3.47) and Hispanic (aRR = 1.92, 95% CI: 1.17-3.14) women were more likely to suffer from it than White women.

The researchers report that “cesarean birth accounted for an estimated 15.8% (95% CI: 2.1%-48.7%) and 16.5% (95% CI: 4.0%-44.0%) of excess maternal morbidity among non-Hispanic Black and Hispanic people, respectively.”

“Both endometritis and wound complications are much more common among individuals with cesarean, and blood clots, hysterectomy, and ICU admission are also more common after cesarean compared with vaginal delivery,” Dr. Debbink said.

The message of the study, she said, is that the health care system “perpetuates gaps in cesarean delivery for Black and Hispanic individuals compared to White individuals” even in low-risk, first-time live births. “We do not yet know exactly what the right levers are to address this gap, but it is important that we ob-gyns examine our practice patterns and our hospitals’ practice patterns to ensure equity for all our patients.”

Rebecca Delafield, PhD, an assistant professor of Native Hawaiian Health at the University of Hawaii, praised the study as “well-conducted” in an interview. “I agree with the assessment that while the cesarean delivery accounts for a modest proportion of excess morbidity in this study, the impact at the population level is significant,” said Dr. Delafield, who studies health disparities and didn’t take part in the study. “Delivery is complex and the causes of disparities observed are likely multifactorial, therefore research such as this is necessary and compelling.”

She added: “It is becoming increasingly evident that studies investigating racial/ethnic disparities in cesarean delivery and other maternal health outcomes must look beyond maternal behavioral or medical risk factors – e.g., obesity or hypertension – and consider the contribution of a broader set of factors, including societal prejudices.”

The study is funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Advancing Translational Sciences. One study author reports funding from GlaxoSmithKline, Pfizer, Moderna, and UpToDate (contributor) and from the Centers for Disease Control and Prevention (via her institution). Dr. Debbink, the other authors, and Dr. Delafield report no disclosures.

Older Canadian schoolchildren who spent the most time looking at screens during the COVID-19 pandemic experienced higher levels of anxiety and depression, while their younger counterparts had more conduct problems, researchers have found. However, the study doesn’t definitively prove that screen time is harmful, and an expert challenged the conclusions.

Still, the findings highlight the potential harms of excessive screen time, especially in the context of pandemic-era virtual learning. Clinicians “really need to advocate for policies that would be protective for children to reduce their screen time and social isolation and increase their involvement with school, sports, and academic activities,” Catherine S. Birken, MD, a pediatrician at the University of Toronto and study coauthor said in an interview.

The study appeared Dec. 28, 2021, in the journal JAMA Network Open (doi: 10.1001/jamanetworkopen.2021.40875).

Dr. Birken and colleagues launched the study to examine whether heightened levels of screen time during the pandemic disrupted mental health in kids. In particular, they wanted to break down different types of screen time, such as virtual learning, watching television, and playing video games.

“The bulk of the literature is supportive of a strong relationship between screen time and mental health symptoms like anxiety,” Dr. Birken said.

For the study, the researchers surveyed parents to track the screen time of 2,026 children between May 2020 and April 2021.

In a cohort of 532 younger children (average age, 5.9 years; 52% male; 58% of European ancestry), the researchers linked each extra daily hour of TV or use of digital media to worse behavior, as measured by the Strengths and Difficulties Questionnaire: 0.22 in an adjusted model for children aged 2-4;(95% confidence interval, 0.10-0.35; P < .001) and 0.07 in an adjusted model in those aged 4 and older (95% CI, 0.02-0.11; P = .007).

However, the researchers observed no statistically significant links to more anxiety/depression or hyperactivity/inattention in this group of children.

Among 1,494 older kids (mean age, 11.3; 57% male; 58% of European ancestry), researchers linked greater daily use of TV or digital media to higher levels of depression symptoms in a dose-dependent relationship, Dr. Birken said (1 hour: beta, 0.21; 95% CI, –1.28 to 0.78; 2-3 hours: beta, 1.81; 95% CI, 0.29-3.33; 4-5 hours: beta, 2.80; 95% CI, 1.15-4.44; 6-8 hours: beta, 5.16; 95% CI, 3.32-7.01; 9 hours: beta, 5.42; 95% CI, 3.30-7.54; overall P < .001).

“Similarly, higher TV or digital media time per day was associated with higher levels of anxiety symptoms,” the researchers reported. “TV or digital media time per day was also significantly associated with differences in symptoms of irritability, inattention, and hyperactivity/inattention.”

More time spent learning virtually was associated with higher levels of depression and anxiety in both groups of children, according to the researchers. Whether this finding reflects an effect of screens themselves or because the children most exposed to virtual learning may also have been the most exposed to the stressful disruptiveness of the pandemic is unclear.

The researchers also found “insufficient evidence” to link more virtual learning to irritability, inattention and hyperactivity, inattention, and hyperactivity/impulsivity in adjusted models.

Video chatting did not appear to have a protective effect, Dr. Birken said. The researchers also specifically analyzed children with autism and found no link between more screen time and various mental health/conduct problems.

Is it possible that kids with more anxiety, depression, and isolation simply turn to screens because they’re anxious, depressed, and isolated? Dr. Birken said the researchers adjusted the findings to account for previous mental health problems. And she noted that the study linked more pandemic-era virtual learning to more depression/anxiety. It’s “hard to imagine” how more mental health problems would cause more virtual learning.
 

Bad news or bad stats?

Chris Ferguson, PhD, a professor of psychology at Stetson University. DeLand, Fla., who studies screen time, criticized the study in an interview. “The observed effects are so tiny, it’s impossible to know if they are real or a false-positive artifact common to social science research,” he said. “Ultimately, this study is better evidence about how many scholars are bad at statistics than anything having to do with kids and screens.”

Dr. Ferguson said that the results may be confounded because kids turn to screens to reduce their anxiety. “For the most part, screens were a godsend during COVID-19,” he said. “They helped kids stay inside and gave them something to do while social distancing and allowed them to keep in touch with friends and families. Honestly, what else were we expecting kids to do, stare at the wallpaper?”

Children with depression and anxiety often retreat into screens or books to escape the unpleasantries of real life. “That doesn’t mean the screens or books are the culprits,” he said.

Instead of focusing on screen time, Dr. Ferguson suggested parents consider these factors: “Keeping in mind not every kid is a genius, is your kid doing about as well in school as you’d expect, given their natural ability? Are they getting at least some exercise every day? Are they getting adequate sleep? Are they able to socialize with friends in some context, either in real life or online? Are they happy?”

The study was funded by the Canadian Institutes of Health Research, the Center for Brain & Mental Health at The Hospital for Sick Children, the Ontario Ministry of Health, and the Miner’s Lamp Innovation Fund in Prevention and Early Detection of Severe Mental Illness at the University of Toronto. The study authors reported various financial relationships. Dr. Ferguson reported no relevant financial conflicts of interest.

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

Older Canadian schoolchildren who spent the most time looking at screens during the COVID-19 pandemic experienced higher levels of anxiety and depression, while their younger counterparts had more conduct problems, researchers have found. However, the study doesn’t definitively prove that screen time is harmful, and an expert challenged the conclusions.

Still, the findings highlight the potential harms of excessive screen time, especially in the context of pandemic-era virtual learning. Clinicians “really need to advocate for policies that would be protective for children to reduce their screen time and social isolation and increase their involvement with school, sports, and academic activities,” Catherine S. Birken, MD, a pediatrician at the University of Toronto and study coauthor said in an interview.

The study appeared Dec. 28, 2021, in the journal JAMA Network Open (doi: 10.1001/jamanetworkopen.2021.40875).

Dr. Birken and colleagues launched the study to examine whether heightened levels of screen time during the pandemic disrupted mental health in kids. In particular, they wanted to break down different types of screen time, such as virtual learning, watching television, and playing video games.

“The bulk of the literature is supportive of a strong relationship between screen time and mental health symptoms like anxiety,” Dr. Birken said.

For the study, the researchers surveyed parents to track the screen time of 2,026 children between May 2020 and April 2021.

In a cohort of 532 younger children (average age, 5.9 years; 52% male; 58% of European ancestry), the researchers linked each extra daily hour of TV or use of digital media to worse behavior, as measured by the Strengths and Difficulties Questionnaire: 0.22 in an adjusted model for children aged 2-4;(95% confidence interval, 0.10-0.35; P < .001) and 0.07 in an adjusted model in those aged 4 and older (95% CI, 0.02-0.11; P = .007).

However, the researchers observed no statistically significant links to more anxiety/depression or hyperactivity/inattention in this group of children.

Among 1,494 older kids (mean age, 11.3; 57% male; 58% of European ancestry), researchers linked greater daily use of TV or digital media to higher levels of depression symptoms in a dose-dependent relationship, Dr. Birken said (1 hour: beta, 0.21; 95% CI, –1.28 to 0.78; 2-3 hours: beta, 1.81; 95% CI, 0.29-3.33; 4-5 hours: beta, 2.80; 95% CI, 1.15-4.44; 6-8 hours: beta, 5.16; 95% CI, 3.32-7.01; 9 hours: beta, 5.42; 95% CI, 3.30-7.54; overall P < .001).

“Similarly, higher TV or digital media time per day was associated with higher levels of anxiety symptoms,” the researchers reported. “TV or digital media time per day was also significantly associated with differences in symptoms of irritability, inattention, and hyperactivity/inattention.”

More time spent learning virtually was associated with higher levels of depression and anxiety in both groups of children, according to the researchers. Whether this finding reflects an effect of screens themselves or because the children most exposed to virtual learning may also have been the most exposed to the stressful disruptiveness of the pandemic is unclear.

The researchers also found “insufficient evidence” to link more virtual learning to irritability, inattention and hyperactivity, inattention, and hyperactivity/impulsivity in adjusted models.

Video chatting did not appear to have a protective effect, Dr. Birken said. The researchers also specifically analyzed children with autism and found no link between more screen time and various mental health/conduct problems.

Is it possible that kids with more anxiety, depression, and isolation simply turn to screens because they’re anxious, depressed, and isolated? Dr. Birken said the researchers adjusted the findings to account for previous mental health problems. And she noted that the study linked more pandemic-era virtual learning to more depression/anxiety. It’s “hard to imagine” how more mental health problems would cause more virtual learning.
 

Bad news or bad stats?

Chris Ferguson, PhD, a professor of psychology at Stetson University. DeLand, Fla., who studies screen time, criticized the study in an interview. “The observed effects are so tiny, it’s impossible to know if they are real or a false-positive artifact common to social science research,” he said. “Ultimately, this study is better evidence about how many scholars are bad at statistics than anything having to do with kids and screens.”

Dr. Ferguson said that the results may be confounded because kids turn to screens to reduce their anxiety. “For the most part, screens were a godsend during COVID-19,” he said. “They helped kids stay inside and gave them something to do while social distancing and allowed them to keep in touch with friends and families. Honestly, what else were we expecting kids to do, stare at the wallpaper?”

Children with depression and anxiety often retreat into screens or books to escape the unpleasantries of real life. “That doesn’t mean the screens or books are the culprits,” he said.

Instead of focusing on screen time, Dr. Ferguson suggested parents consider these factors: “Keeping in mind not every kid is a genius, is your kid doing about as well in school as you’d expect, given their natural ability? Are they getting at least some exercise every day? Are they getting adequate sleep? Are they able to socialize with friends in some context, either in real life or online? Are they happy?”

The study was funded by the Canadian Institutes of Health Research, the Center for Brain & Mental Health at The Hospital for Sick Children, the Ontario Ministry of Health, and the Miner’s Lamp Innovation Fund in Prevention and Early Detection of Severe Mental Illness at the University of Toronto. The study authors reported various financial relationships. Dr. Ferguson reported no relevant financial conflicts of interest.

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

Older Canadian schoolchildren who spent the most time looking at screens during the COVID-19 pandemic experienced higher levels of anxiety and depression, while their younger counterparts had more conduct problems, researchers have found. However, the study doesn’t definitively prove that screen time is harmful, and an expert challenged the conclusions.

Still, the findings highlight the potential harms of excessive screen time, especially in the context of pandemic-era virtual learning. Clinicians “really need to advocate for policies that would be protective for children to reduce their screen time and social isolation and increase their involvement with school, sports, and academic activities,” Catherine S. Birken, MD, a pediatrician at the University of Toronto and study coauthor said in an interview.

The study appeared Dec. 28, 2021, in the journal JAMA Network Open (doi: 10.1001/jamanetworkopen.2021.40875).

Dr. Birken and colleagues launched the study to examine whether heightened levels of screen time during the pandemic disrupted mental health in kids. In particular, they wanted to break down different types of screen time, such as virtual learning, watching television, and playing video games.

“The bulk of the literature is supportive of a strong relationship between screen time and mental health symptoms like anxiety,” Dr. Birken said.

For the study, the researchers surveyed parents to track the screen time of 2,026 children between May 2020 and April 2021.

In a cohort of 532 younger children (average age, 5.9 years; 52% male; 58% of European ancestry), the researchers linked each extra daily hour of TV or use of digital media to worse behavior, as measured by the Strengths and Difficulties Questionnaire: 0.22 in an adjusted model for children aged 2-4;(95% confidence interval, 0.10-0.35; P < .001) and 0.07 in an adjusted model in those aged 4 and older (95% CI, 0.02-0.11; P = .007).

However, the researchers observed no statistically significant links to more anxiety/depression or hyperactivity/inattention in this group of children.

Among 1,494 older kids (mean age, 11.3; 57% male; 58% of European ancestry), researchers linked greater daily use of TV or digital media to higher levels of depression symptoms in a dose-dependent relationship, Dr. Birken said (1 hour: beta, 0.21; 95% CI, –1.28 to 0.78; 2-3 hours: beta, 1.81; 95% CI, 0.29-3.33; 4-5 hours: beta, 2.80; 95% CI, 1.15-4.44; 6-8 hours: beta, 5.16; 95% CI, 3.32-7.01; 9 hours: beta, 5.42; 95% CI, 3.30-7.54; overall P < .001).

“Similarly, higher TV or digital media time per day was associated with higher levels of anxiety symptoms,” the researchers reported. “TV or digital media time per day was also significantly associated with differences in symptoms of irritability, inattention, and hyperactivity/inattention.”

More time spent learning virtually was associated with higher levels of depression and anxiety in both groups of children, according to the researchers. Whether this finding reflects an effect of screens themselves or because the children most exposed to virtual learning may also have been the most exposed to the stressful disruptiveness of the pandemic is unclear.

The researchers also found “insufficient evidence” to link more virtual learning to irritability, inattention and hyperactivity, inattention, and hyperactivity/impulsivity in adjusted models.

Video chatting did not appear to have a protective effect, Dr. Birken said. The researchers also specifically analyzed children with autism and found no link between more screen time and various mental health/conduct problems.

Is it possible that kids with more anxiety, depression, and isolation simply turn to screens because they’re anxious, depressed, and isolated? Dr. Birken said the researchers adjusted the findings to account for previous mental health problems. And she noted that the study linked more pandemic-era virtual learning to more depression/anxiety. It’s “hard to imagine” how more mental health problems would cause more virtual learning.
 

Bad news or bad stats?

Chris Ferguson, PhD, a professor of psychology at Stetson University. DeLand, Fla., who studies screen time, criticized the study in an interview. “The observed effects are so tiny, it’s impossible to know if they are real or a false-positive artifact common to social science research,” he said. “Ultimately, this study is better evidence about how many scholars are bad at statistics than anything having to do with kids and screens.”

Dr. Ferguson said that the results may be confounded because kids turn to screens to reduce their anxiety. “For the most part, screens were a godsend during COVID-19,” he said. “They helped kids stay inside and gave them something to do while social distancing and allowed them to keep in touch with friends and families. Honestly, what else were we expecting kids to do, stare at the wallpaper?”

Children with depression and anxiety often retreat into screens or books to escape the unpleasantries of real life. “That doesn’t mean the screens or books are the culprits,” he said.

Instead of focusing on screen time, Dr. Ferguson suggested parents consider these factors: “Keeping in mind not every kid is a genius, is your kid doing about as well in school as you’d expect, given their natural ability? Are they getting at least some exercise every day? Are they getting adequate sleep? Are they able to socialize with friends in some context, either in real life or online? Are they happy?”

The study was funded by the Canadian Institutes of Health Research, the Center for Brain & Mental Health at The Hospital for Sick Children, the Ontario Ministry of Health, and the Miner’s Lamp Innovation Fund in Prevention and Early Detection of Severe Mental Illness at the University of Toronto. The study authors reported various financial relationships. Dr. Ferguson reported no relevant financial conflicts of interest.

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

Many older adults with epilepsy are misdiagnosed even though the highest incidence of the disease is in people over 75, a neurologist told an audience at the annual meeting of the American Epilepsy Society. She urged colleagues to focus on possible interactions with other neurological conditions, consider various complicating factors, and embrace a team strategy.

“There are lots of nuances,” said Rebecca O’Dwyer, MD, an adult epilepsy specialist with Rush Epilepsy Center in Chicago. “It takes a lot of time and requires a multidisciplinary approach. Taking care of older individuals with epilepsy truly is a team sport.”

According to a 2014 report highlighted by Dr. O’Dwyer, “nearly 25% of new-onset seizures occur after age 65. The incidence of epilepsy in this age group is almost twice the rate in children, and in people over age 80, it is triple the rate in children.”

Research suggests it can take up to 2 years to correctly diagnose epilepsy in older people, Dr. O’Dwyer said, and nearly two-thirds of cases may be misdiagnosed. “Some of it is just limited awareness. There’s this perception in the public that epilepsy is something that occurs in younger adults or young children, and that when you come to a certain age, you cannot have epilepsy. Also, there are differences in the clinical manifestations of their seizures, and many comorbid possibilities could also present in similar fashion to epilepsy. Some of our usual tools that we use to come to the diagnosis such as EEG are also known to be less sensitive in this age group.”

According to the 2014 report, research finds that the elderly are much more likely than young adults to have postictal sleepiness or unresponsiveness and seizures manifesting as brief moments of subtle confusion. They’re much less likely to have epileptic aura and generalized tonic seizures.

“An epileptic seizure in an older adult tends to be less dramatic with fewer motor manifestations, and they often tend to be monophasic. They may be so subtle that they’re missed by family members and other medical providers,” Dr. O’Dwyer said. “I had a patient whose seizure consisted of her tapping her left shoulder. She had been doing this for at least 6 months, and she came to my clinic after her daughter realized that she was a little confused afterward. She’d already seen a behavioral neurologist and been given the diagnosis of dementia. We were fortunate enough to catch one of these episodes while we were doing an EEG, and we diagnosed her with focal epilepsy. With one antiseizure medication, we stopped the seizures, and her memory came back.”

Make sure to take detailed histories and keep an eye out for descriptions of behaviors that are episodic but perhaps not typical of seizures, she said.

Epilepsy can be misdiagnosed as a variety of conditions, she said, such as syncope, Alzheimer’s disease, stroke, Parkinson’s disease, and atrial fibrillation. “When you do diagnose somebody older with new-onset epilepsy, you should work them up for a stroke. Because we know that within the first 4 weeks after their first seizure the likelihood that they could have a stroke is three times higher.”

It’s also possible that neurological conditions can be followed by new-onset epilepsy, she said, making dementia even worse. Low-dose antiepileptic drugs can be helpful in these patients.

But seniors are especially vulnerable to side effects of antiepileptic drugs such as sedation, dizziness, and cardiac-conduction abnormalities. “You must adhere to the mantra of going low and going slow because they are exquisitely susceptible,” Dr. O’Dwyer said.

She recommends lamotrigine, which is well tolerated with helpful mood-stabilizing effects, and levetiracetam, which attenuates cognitive decline in dementia but may cause side effects such as irritable mood. Zonisamide is showing promise in patients with parkinsonian syndromes, she said, and it may be helpful to maximize drugs that patients are already taking such as gabapentin or pregabalin.

Finally, Dr. O’Dwyer urged colleagues to work in teams that include caregivers, primary care doctors, social workers, and pharmacists. “Sometimes in all this,” she said, “my job is the easiest.”

Dr. O’Dwyer discloses research support from the Shapiro Foundation.

Many older adults with epilepsy are misdiagnosed even though the highest incidence of the disease is in people over 75, a neurologist told an audience at the annual meeting of the American Epilepsy Society. She urged colleagues to focus on possible interactions with other neurological conditions, consider various complicating factors, and embrace a team strategy.

“There are lots of nuances,” said Rebecca O’Dwyer, MD, an adult epilepsy specialist with Rush Epilepsy Center in Chicago. “It takes a lot of time and requires a multidisciplinary approach. Taking care of older individuals with epilepsy truly is a team sport.”

According to a 2014 report highlighted by Dr. O’Dwyer, “nearly 25% of new-onset seizures occur after age 65. The incidence of epilepsy in this age group is almost twice the rate in children, and in people over age 80, it is triple the rate in children.”

Research suggests it can take up to 2 years to correctly diagnose epilepsy in older people, Dr. O’Dwyer said, and nearly two-thirds of cases may be misdiagnosed. “Some of it is just limited awareness. There’s this perception in the public that epilepsy is something that occurs in younger adults or young children, and that when you come to a certain age, you cannot have epilepsy. Also, there are differences in the clinical manifestations of their seizures, and many comorbid possibilities could also present in similar fashion to epilepsy. Some of our usual tools that we use to come to the diagnosis such as EEG are also known to be less sensitive in this age group.”

According to the 2014 report, research finds that the elderly are much more likely than young adults to have postictal sleepiness or unresponsiveness and seizures manifesting as brief moments of subtle confusion. They’re much less likely to have epileptic aura and generalized tonic seizures.

“An epileptic seizure in an older adult tends to be less dramatic with fewer motor manifestations, and they often tend to be monophasic. They may be so subtle that they’re missed by family members and other medical providers,” Dr. O’Dwyer said. “I had a patient whose seizure consisted of her tapping her left shoulder. She had been doing this for at least 6 months, and she came to my clinic after her daughter realized that she was a little confused afterward. She’d already seen a behavioral neurologist and been given the diagnosis of dementia. We were fortunate enough to catch one of these episodes while we were doing an EEG, and we diagnosed her with focal epilepsy. With one antiseizure medication, we stopped the seizures, and her memory came back.”

Make sure to take detailed histories and keep an eye out for descriptions of behaviors that are episodic but perhaps not typical of seizures, she said.

Epilepsy can be misdiagnosed as a variety of conditions, she said, such as syncope, Alzheimer’s disease, stroke, Parkinson’s disease, and atrial fibrillation. “When you do diagnose somebody older with new-onset epilepsy, you should work them up for a stroke. Because we know that within the first 4 weeks after their first seizure the likelihood that they could have a stroke is three times higher.”

It’s also possible that neurological conditions can be followed by new-onset epilepsy, she said, making dementia even worse. Low-dose antiepileptic drugs can be helpful in these patients.

But seniors are especially vulnerable to side effects of antiepileptic drugs such as sedation, dizziness, and cardiac-conduction abnormalities. “You must adhere to the mantra of going low and going slow because they are exquisitely susceptible,” Dr. O’Dwyer said.

She recommends lamotrigine, which is well tolerated with helpful mood-stabilizing effects, and levetiracetam, which attenuates cognitive decline in dementia but may cause side effects such as irritable mood. Zonisamide is showing promise in patients with parkinsonian syndromes, she said, and it may be helpful to maximize drugs that patients are already taking such as gabapentin or pregabalin.

Finally, Dr. O’Dwyer urged colleagues to work in teams that include caregivers, primary care doctors, social workers, and pharmacists. “Sometimes in all this,” she said, “my job is the easiest.”

Dr. O’Dwyer discloses research support from the Shapiro Foundation.

Many older adults with epilepsy are misdiagnosed even though the highest incidence of the disease is in people over 75, a neurologist told an audience at the annual meeting of the American Epilepsy Society. She urged colleagues to focus on possible interactions with other neurological conditions, consider various complicating factors, and embrace a team strategy.

“There are lots of nuances,” said Rebecca O’Dwyer, MD, an adult epilepsy specialist with Rush Epilepsy Center in Chicago. “It takes a lot of time and requires a multidisciplinary approach. Taking care of older individuals with epilepsy truly is a team sport.”

According to a 2014 report highlighted by Dr. O’Dwyer, “nearly 25% of new-onset seizures occur after age 65. The incidence of epilepsy in this age group is almost twice the rate in children, and in people over age 80, it is triple the rate in children.”

Research suggests it can take up to 2 years to correctly diagnose epilepsy in older people, Dr. O’Dwyer said, and nearly two-thirds of cases may be misdiagnosed. “Some of it is just limited awareness. There’s this perception in the public that epilepsy is something that occurs in younger adults or young children, and that when you come to a certain age, you cannot have epilepsy. Also, there are differences in the clinical manifestations of their seizures, and many comorbid possibilities could also present in similar fashion to epilepsy. Some of our usual tools that we use to come to the diagnosis such as EEG are also known to be less sensitive in this age group.”

According to the 2014 report, research finds that the elderly are much more likely than young adults to have postictal sleepiness or unresponsiveness and seizures manifesting as brief moments of subtle confusion. They’re much less likely to have epileptic aura and generalized tonic seizures.

“An epileptic seizure in an older adult tends to be less dramatic with fewer motor manifestations, and they often tend to be monophasic. They may be so subtle that they’re missed by family members and other medical providers,” Dr. O’Dwyer said. “I had a patient whose seizure consisted of her tapping her left shoulder. She had been doing this for at least 6 months, and she came to my clinic after her daughter realized that she was a little confused afterward. She’d already seen a behavioral neurologist and been given the diagnosis of dementia. We were fortunate enough to catch one of these episodes while we were doing an EEG, and we diagnosed her with focal epilepsy. With one antiseizure medication, we stopped the seizures, and her memory came back.”

Make sure to take detailed histories and keep an eye out for descriptions of behaviors that are episodic but perhaps not typical of seizures, she said.

Epilepsy can be misdiagnosed as a variety of conditions, she said, such as syncope, Alzheimer’s disease, stroke, Parkinson’s disease, and atrial fibrillation. “When you do diagnose somebody older with new-onset epilepsy, you should work them up for a stroke. Because we know that within the first 4 weeks after their first seizure the likelihood that they could have a stroke is three times higher.”

It’s also possible that neurological conditions can be followed by new-onset epilepsy, she said, making dementia even worse. Low-dose antiepileptic drugs can be helpful in these patients.

But seniors are especially vulnerable to side effects of antiepileptic drugs such as sedation, dizziness, and cardiac-conduction abnormalities. “You must adhere to the mantra of going low and going slow because they are exquisitely susceptible,” Dr. O’Dwyer said.

She recommends lamotrigine, which is well tolerated with helpful mood-stabilizing effects, and levetiracetam, which attenuates cognitive decline in dementia but may cause side effects such as irritable mood. Zonisamide is showing promise in patients with parkinsonian syndromes, she said, and it may be helpful to maximize drugs that patients are already taking such as gabapentin or pregabalin.

Finally, Dr. O’Dwyer urged colleagues to work in teams that include caregivers, primary care doctors, social workers, and pharmacists. “Sometimes in all this,” she said, “my job is the easiest.”

Dr. O’Dwyer discloses research support from the Shapiro Foundation.

Despite a flurry of publicity about its newfound cardiac risk profile, the antiseizure medication lamotrigine (Lamictal) is “still a good drug” in epilepsy and an excellent treatment for certain groups, New York University neurologist Jacqueline A. French, MD, told colleagues at the annual meeting of the American Epilepsy Society. But it’s now crucial to take special precautions in high-risk groups such as older people and heart patients.

“We need to plan more carefully when we use it, which we hate to do, as we know. But we’ve still got to do it,” said Dr. French, former president of the AES. “The risks are very small, but keep in mind that they’re not zero.”

In October 2020, the Food and Drug Administration added a warning to the lamotrigine label that said the drug “could slow ventricular conduction (widen QRS) and induce proarrhythmia, including sudden death, in patients with structural heart disease or myocardial ischemia.”

The FDA recommended avoiding the sodium channel blocker’s use “in patients who have cardiac conduction disorders (e.g., second- or third-degree heart block), ventricular arrhythmias, or cardiac disease or abnormality (e.g., myocardial ischemia, heart failure, structural heart disease, Brugada syndrome, or other sodium channelopathies). Concomitant use of other sodium channel blockers may increase the risk of proarrhythmia.”

Later, in March 2021, the FDA announced that a review of in vitro findings “showed a potential increased risk of heart rhythm problems.”

As Dr. French noted, lamotrigine remains widely prescribed even though there’s “no pharmaceutical company out there pushing [it].” It’s an especially beneficial drug for certain groups such as the elderly and women of child-bearing age, she said.

But older people are also at higher risk of drug-related heart complications because of the fact that many already have cardiac disease, Dr. French said. She highlighted a 2005 trial of lamotrigine that found 48% of 593 patients aged 60 years and older had cardiac disease.
 

Special precautions

So what should neurologists know about prescribing lamotrigine in light of the new warning? Dr. French recommended guidelines that she cowrote with the AES and International League Against Epilepsy.

• Prescribe as normal in patients under 60 with no cardiac risk factors. In patients older than 60, or younger with risk factors, consider an EKG before prescribing lamotrigine.
• “Nonspecific EKG abnormalities (e.g., nonspecific ST and T wave abnormalities) are not concerning, and should not preclude these individuals from being prescribed lamotrigine.”
• Beware of higher risk and consider consulting a cardiologist before starting treatment in patients with second- or third-degree heart block, Brugada syndrome, arrhythmogenic ventricular cardiomyopathy, left bundle branch block, and right bundle branch block with left anterior or posterior fascicular block.
• “In most cases the initial EKG can be obtained while titrating, mainly when the individual is at the first dose of 25 mg/day because lamotrigine must be titrated slowly, and because cardiac adverse events are dose related.”
• “Clinicians should consider obtaining an EKG and/or cardiology consultation in people on lamotrigine with sudden-onset syncope or presyncope with loss of muscular tone without a clear vasovagal or orthostatic cause.”

Dr. French cautioned colleagues that they shouldn’t assume that lamotrigine stands alone among sodium channel blockers in terms of cardiac risk. As she noted, the FDA is asking manufacturers of other drugs in that class to provide data. “At some point, maybe sometime in the near future, we are going to hear in this particular in vitro sense how the other sodium channel blockers do stack up, compared with lamotrigine. At presence, in the absence of the availability of all of the rest of the data, it would be incorrect to presume that lamotrigine has more cardiac effects than other sodium channel blocking antiseizure medicines or all antiseizure medicines.”

For now, she said, although the guidelines are for lamotrigine, it’s “prudent” to follow them for all sodium channel blockers.

Dr. French reported no disclosures.

Despite a flurry of publicity about its newfound cardiac risk profile, the antiseizure medication lamotrigine (Lamictal) is “still a good drug” in epilepsy and an excellent treatment for certain groups, New York University neurologist Jacqueline A. French, MD, told colleagues at the annual meeting of the American Epilepsy Society. But it’s now crucial to take special precautions in high-risk groups such as older people and heart patients.

“We need to plan more carefully when we use it, which we hate to do, as we know. But we’ve still got to do it,” said Dr. French, former president of the AES. “The risks are very small, but keep in mind that they’re not zero.”

In October 2020, the Food and Drug Administration added a warning to the lamotrigine label that said the drug “could slow ventricular conduction (widen QRS) and induce proarrhythmia, including sudden death, in patients with structural heart disease or myocardial ischemia.”

The FDA recommended avoiding the sodium channel blocker’s use “in patients who have cardiac conduction disorders (e.g., second- or third-degree heart block), ventricular arrhythmias, or cardiac disease or abnormality (e.g., myocardial ischemia, heart failure, structural heart disease, Brugada syndrome, or other sodium channelopathies). Concomitant use of other sodium channel blockers may increase the risk of proarrhythmia.”

Later, in March 2021, the FDA announced that a review of in vitro findings “showed a potential increased risk of heart rhythm problems.”

As Dr. French noted, lamotrigine remains widely prescribed even though there’s “no pharmaceutical company out there pushing [it].” It’s an especially beneficial drug for certain groups such as the elderly and women of child-bearing age, she said.

But older people are also at higher risk of drug-related heart complications because of the fact that many already have cardiac disease, Dr. French said. She highlighted a 2005 trial of lamotrigine that found 48% of 593 patients aged 60 years and older had cardiac disease.
 

Special precautions

So what should neurologists know about prescribing lamotrigine in light of the new warning? Dr. French recommended guidelines that she cowrote with the AES and International League Against Epilepsy.

• Prescribe as normal in patients under 60 with no cardiac risk factors. In patients older than 60, or younger with risk factors, consider an EKG before prescribing lamotrigine.
• “Nonspecific EKG abnormalities (e.g., nonspecific ST and T wave abnormalities) are not concerning, and should not preclude these individuals from being prescribed lamotrigine.”
• Beware of higher risk and consider consulting a cardiologist before starting treatment in patients with second- or third-degree heart block, Brugada syndrome, arrhythmogenic ventricular cardiomyopathy, left bundle branch block, and right bundle branch block with left anterior or posterior fascicular block.
• “In most cases the initial EKG can be obtained while titrating, mainly when the individual is at the first dose of 25 mg/day because lamotrigine must be titrated slowly, and because cardiac adverse events are dose related.”
• “Clinicians should consider obtaining an EKG and/or cardiology consultation in people on lamotrigine with sudden-onset syncope or presyncope with loss of muscular tone without a clear vasovagal or orthostatic cause.”

Dr. French cautioned colleagues that they shouldn’t assume that lamotrigine stands alone among sodium channel blockers in terms of cardiac risk. As she noted, the FDA is asking manufacturers of other drugs in that class to provide data. “At some point, maybe sometime in the near future, we are going to hear in this particular in vitro sense how the other sodium channel blockers do stack up, compared with lamotrigine. At presence, in the absence of the availability of all of the rest of the data, it would be incorrect to presume that lamotrigine has more cardiac effects than other sodium channel blocking antiseizure medicines or all antiseizure medicines.”

For now, she said, although the guidelines are for lamotrigine, it’s “prudent” to follow them for all sodium channel blockers.

Dr. French reported no disclosures.

Despite a flurry of publicity about its newfound cardiac risk profile, the antiseizure medication lamotrigine (Lamictal) is “still a good drug” in epilepsy and an excellent treatment for certain groups, New York University neurologist Jacqueline A. French, MD, told colleagues at the annual meeting of the American Epilepsy Society. But it’s now crucial to take special precautions in high-risk groups such as older people and heart patients.

“We need to plan more carefully when we use it, which we hate to do, as we know. But we’ve still got to do it,” said Dr. French, former president of the AES. “The risks are very small, but keep in mind that they’re not zero.”

In October 2020, the Food and Drug Administration added a warning to the lamotrigine label that said the drug “could slow ventricular conduction (widen QRS) and induce proarrhythmia, including sudden death, in patients with structural heart disease or myocardial ischemia.”

The FDA recommended avoiding the sodium channel blocker’s use “in patients who have cardiac conduction disorders (e.g., second- or third-degree heart block), ventricular arrhythmias, or cardiac disease or abnormality (e.g., myocardial ischemia, heart failure, structural heart disease, Brugada syndrome, or other sodium channelopathies). Concomitant use of other sodium channel blockers may increase the risk of proarrhythmia.”

Later, in March 2021, the FDA announced that a review of in vitro findings “showed a potential increased risk of heart rhythm problems.”

As Dr. French noted, lamotrigine remains widely prescribed even though there’s “no pharmaceutical company out there pushing [it].” It’s an especially beneficial drug for certain groups such as the elderly and women of child-bearing age, she said.

But older people are also at higher risk of drug-related heart complications because of the fact that many already have cardiac disease, Dr. French said. She highlighted a 2005 trial of lamotrigine that found 48% of 593 patients aged 60 years and older had cardiac disease.
 

Special precautions

So what should neurologists know about prescribing lamotrigine in light of the new warning? Dr. French recommended guidelines that she cowrote with the AES and International League Against Epilepsy.

• Prescribe as normal in patients under 60 with no cardiac risk factors. In patients older than 60, or younger with risk factors, consider an EKG before prescribing lamotrigine.
• “Nonspecific EKG abnormalities (e.g., nonspecific ST and T wave abnormalities) are not concerning, and should not preclude these individuals from being prescribed lamotrigine.”
• Beware of higher risk and consider consulting a cardiologist before starting treatment in patients with second- or third-degree heart block, Brugada syndrome, arrhythmogenic ventricular cardiomyopathy, left bundle branch block, and right bundle branch block with left anterior or posterior fascicular block.
• “In most cases the initial EKG can be obtained while titrating, mainly when the individual is at the first dose of 25 mg/day because lamotrigine must be titrated slowly, and because cardiac adverse events are dose related.”
• “Clinicians should consider obtaining an EKG and/or cardiology consultation in people on lamotrigine with sudden-onset syncope or presyncope with loss of muscular tone without a clear vasovagal or orthostatic cause.”

Dr. French cautioned colleagues that they shouldn’t assume that lamotrigine stands alone among sodium channel blockers in terms of cardiac risk. As she noted, the FDA is asking manufacturers of other drugs in that class to provide data. “At some point, maybe sometime in the near future, we are going to hear in this particular in vitro sense how the other sodium channel blockers do stack up, compared with lamotrigine. At presence, in the absence of the availability of all of the rest of the data, it would be incorrect to presume that lamotrigine has more cardiac effects than other sodium channel blocking antiseizure medicines or all antiseizure medicines.”

For now, she said, although the guidelines are for lamotrigine, it’s “prudent” to follow them for all sodium channel blockers.

Dr. French reported no disclosures.

Physicians at a Boston hospital adjusted medical management for nearly three-quarters of patients with infantile- or childhood-onset epilepsy who were diagnosed with genetic epilepsy, researchers reported at the annual meeting of the American Epilepsy Society. The findings provide new insight into the usefulness of genetic tests in children with epilepsy of unknown cause.

“Genetic testing is significantly impacting medical care in a population of individuals with infantile- or childhood-onset epilepsy. Genetic testing should be included as part of the standard evaluation of individuals with unexplained pediatric epilepsy as a means of achieving diagnostic precision and informing clinical management,” study lead author Isabel Haviland, MD, a neurologist with Boston Children’s Hospital/Harvard Medical School, said in an interview.

According to Dr. Haviland, the causes of epilepsy are unexplained in an estimated two-thirds of pediatric epilepsy cases. “Increasingly, when genetic testing is available, previously unexplained cases of pediatric epilepsy are being found to have single-gene etiologies,” she said. “Though a genetic diagnosis in this population has implications for medical care, the direct impact on medical management in a clinical setting has not been measured. We aimed to describe the impact of genetic diagnosis on medical management in a cohort of individuals with pediatric epilepsy.”

Researchers tracked 602 patients at Boston Children’s Hospital who received next-generation gene sequencing testing from 2012 to 2019. Of those, Dr. Haviland said, 152 (25%) had a positive result that indicated genetic epilepsy (46% female, median age of onset = 6 months [2-15 months]). These patients were included in the study.

“We documented an impact on medical management in nearly three-fourths of participants (72%),” Dr. Haviland said. “A genetic diagnosis affected at least one of four categories of medical management, including care coordination (48%), treatment (45%), counseling about a change in prognosis (28%), and change in diagnosis for a few individuals who had a prior established diagnosis (1%).”

As examples, she mentioned three cases:

• Testing revealed that a subject has a disease-causing genetic variant in a gene called PRRT2. “This gene is involved in the release of neurotransmitters in the brain,” Dr. Haviland said. “Thanks to his diagnosis, he was treated with the antiseizure medication oxcarbazepine, which is often effective for epilepsy caused by variants in this gene. He had excellent response to the medication and later became seizure free.”
• A subject had a variation in the SCN1A gene that causes types of epilepsy. “At the time of his diagnosis, there was a trial for a medication called fenfluramine being offered for individuals with SCN1A variants, and his family elected to participate,” she said. “This medication was later approved by the [Food and Drug Administration] for SCN1A-related epilepsy.”
• Testing identified disease-causing variant in the GRIN2A gene in another subject. “This gene is involved in brain cell communication,” Dr. Haviland said. “This individual was treated with memantine, which acts on the specific biological pathway affected by the gene. This treatment would not have been considered without the genetic diagnosis as it is currently only approved for Alzheimer’s disease.”

In addition, Dr. Haviland said, researchers found that “there was impact on medical management both in those with earlier age of epilepsy onset (under 2 years) and those with later age of onset, as well as both in those with developmental disorders (such as autism spectrum disorder, intellectual disability and developmental delay) and those with normal development.

As for the cost of genetic tests, Dr. Haviland pointed to a 2019 study that she said estimated epilepsy panel testing runs from $1,500 to $7,500, and the whole exome sequencing from $4,500 to $7,000. “Insurers sometimes cover testing, but not always,” she said. “In some cases, insurance will only cover testing if it is documented that results will directly alter medical management, which highlights the importance of our findings.”

No study funding was reported. Dr. Haviland and several other authors report no disclosures. One author reports consulting fees from Takeda, Zogenix, Marinus, and FOXG1 Research Foundation. Another author reports research support from the International Foundation for CDKL5 Research.

Physicians at a Boston hospital adjusted medical management for nearly three-quarters of patients with infantile- or childhood-onset epilepsy who were diagnosed with genetic epilepsy, researchers reported at the annual meeting of the American Epilepsy Society. The findings provide new insight into the usefulness of genetic tests in children with epilepsy of unknown cause.

“Genetic testing is significantly impacting medical care in a population of individuals with infantile- or childhood-onset epilepsy. Genetic testing should be included as part of the standard evaluation of individuals with unexplained pediatric epilepsy as a means of achieving diagnostic precision and informing clinical management,” study lead author Isabel Haviland, MD, a neurologist with Boston Children’s Hospital/Harvard Medical School, said in an interview.

According to Dr. Haviland, the causes of epilepsy are unexplained in an estimated two-thirds of pediatric epilepsy cases. “Increasingly, when genetic testing is available, previously unexplained cases of pediatric epilepsy are being found to have single-gene etiologies,” she said. “Though a genetic diagnosis in this population has implications for medical care, the direct impact on medical management in a clinical setting has not been measured. We aimed to describe the impact of genetic diagnosis on medical management in a cohort of individuals with pediatric epilepsy.”

Researchers tracked 602 patients at Boston Children’s Hospital who received next-generation gene sequencing testing from 2012 to 2019. Of those, Dr. Haviland said, 152 (25%) had a positive result that indicated genetic epilepsy (46% female, median age of onset = 6 months [2-15 months]). These patients were included in the study.

“We documented an impact on medical management in nearly three-fourths of participants (72%),” Dr. Haviland said. “A genetic diagnosis affected at least one of four categories of medical management, including care coordination (48%), treatment (45%), counseling about a change in prognosis (28%), and change in diagnosis for a few individuals who had a prior established diagnosis (1%).”

As examples, she mentioned three cases:

• Testing revealed that a subject has a disease-causing genetic variant in a gene called PRRT2. “This gene is involved in the release of neurotransmitters in the brain,” Dr. Haviland said. “Thanks to his diagnosis, he was treated with the antiseizure medication oxcarbazepine, which is often effective for epilepsy caused by variants in this gene. He had excellent response to the medication and later became seizure free.”
• A subject had a variation in the SCN1A gene that causes types of epilepsy. “At the time of his diagnosis, there was a trial for a medication called fenfluramine being offered for individuals with SCN1A variants, and his family elected to participate,” she said. “This medication was later approved by the [Food and Drug Administration] for SCN1A-related epilepsy.”
• Testing identified disease-causing variant in the GRIN2A gene in another subject. “This gene is involved in brain cell communication,” Dr. Haviland said. “This individual was treated with memantine, which acts on the specific biological pathway affected by the gene. This treatment would not have been considered without the genetic diagnosis as it is currently only approved for Alzheimer’s disease.”

In addition, Dr. Haviland said, researchers found that “there was impact on medical management both in those with earlier age of epilepsy onset (under 2 years) and those with later age of onset, as well as both in those with developmental disorders (such as autism spectrum disorder, intellectual disability and developmental delay) and those with normal development.

As for the cost of genetic tests, Dr. Haviland pointed to a 2019 study that she said estimated epilepsy panel testing runs from $1,500 to $7,500, and the whole exome sequencing from $4,500 to $7,000. “Insurers sometimes cover testing, but not always,” she said. “In some cases, insurance will only cover testing if it is documented that results will directly alter medical management, which highlights the importance of our findings.”

No study funding was reported. Dr. Haviland and several other authors report no disclosures. One author reports consulting fees from Takeda, Zogenix, Marinus, and FOXG1 Research Foundation. Another author reports research support from the International Foundation for CDKL5 Research.

Physicians at a Boston hospital adjusted medical management for nearly three-quarters of patients with infantile- or childhood-onset epilepsy who were diagnosed with genetic epilepsy, researchers reported at the annual meeting of the American Epilepsy Society. The findings provide new insight into the usefulness of genetic tests in children with epilepsy of unknown cause.

“Genetic testing is significantly impacting medical care in a population of individuals with infantile- or childhood-onset epilepsy. Genetic testing should be included as part of the standard evaluation of individuals with unexplained pediatric epilepsy as a means of achieving diagnostic precision and informing clinical management,” study lead author Isabel Haviland, MD, a neurologist with Boston Children’s Hospital/Harvard Medical School, said in an interview.

According to Dr. Haviland, the causes of epilepsy are unexplained in an estimated two-thirds of pediatric epilepsy cases. “Increasingly, when genetic testing is available, previously unexplained cases of pediatric epilepsy are being found to have single-gene etiologies,” she said. “Though a genetic diagnosis in this population has implications for medical care, the direct impact on medical management in a clinical setting has not been measured. We aimed to describe the impact of genetic diagnosis on medical management in a cohort of individuals with pediatric epilepsy.”

Researchers tracked 602 patients at Boston Children’s Hospital who received next-generation gene sequencing testing from 2012 to 2019. Of those, Dr. Haviland said, 152 (25%) had a positive result that indicated genetic epilepsy (46% female, median age of onset = 6 months [2-15 months]). These patients were included in the study.

“We documented an impact on medical management in nearly three-fourths of participants (72%),” Dr. Haviland said. “A genetic diagnosis affected at least one of four categories of medical management, including care coordination (48%), treatment (45%), counseling about a change in prognosis (28%), and change in diagnosis for a few individuals who had a prior established diagnosis (1%).”

As examples, she mentioned three cases:

• Testing revealed that a subject has a disease-causing genetic variant in a gene called PRRT2. “This gene is involved in the release of neurotransmitters in the brain,” Dr. Haviland said. “Thanks to his diagnosis, he was treated with the antiseizure medication oxcarbazepine, which is often effective for epilepsy caused by variants in this gene. He had excellent response to the medication and later became seizure free.”
• A subject had a variation in the SCN1A gene that causes types of epilepsy. “At the time of his diagnosis, there was a trial for a medication called fenfluramine being offered for individuals with SCN1A variants, and his family elected to participate,” she said. “This medication was later approved by the [Food and Drug Administration] for SCN1A-related epilepsy.”
• Testing identified disease-causing variant in the GRIN2A gene in another subject. “This gene is involved in brain cell communication,” Dr. Haviland said. “This individual was treated with memantine, which acts on the specific biological pathway affected by the gene. This treatment would not have been considered without the genetic diagnosis as it is currently only approved for Alzheimer’s disease.”

In addition, Dr. Haviland said, researchers found that “there was impact on medical management both in those with earlier age of epilepsy onset (under 2 years) and those with later age of onset, as well as both in those with developmental disorders (such as autism spectrum disorder, intellectual disability and developmental delay) and those with normal development.

As for the cost of genetic tests, Dr. Haviland pointed to a 2019 study that she said estimated epilepsy panel testing runs from $1,500 to $7,500, and the whole exome sequencing from $4,500 to $7,000. “Insurers sometimes cover testing, but not always,” she said. “In some cases, insurance will only cover testing if it is documented that results will directly alter medical management, which highlights the importance of our findings.”

No study funding was reported. Dr. Haviland and several other authors report no disclosures. One author reports consulting fees from Takeda, Zogenix, Marinus, and FOXG1 Research Foundation. Another author reports research support from the International Foundation for CDKL5 Research.

An analysis of hospitalized patients with COVID-19 finds that those with no history of epilepsy had more than 3 times the odds of suffering a new-onset seizure than patients with epilepsy were to have breakthrough seizures (odds radio [OR] 3.15, P < .0001), researchers reported at the annual meeting of the American Epilepsy Society.

“If you have COVID and you have a seizure, it’s more likely that you’re having it for the first time, and it’s not as likely that you have epilepsy,” study lead author Neeraj Singh, MD, a neurologist at the New York-based Northwell Health system, said in an interview. “That’s new. We don’t normally see that when someone has a bacterial or viral infection. It’s demonstrating that this infection is having direct effect on the brain and brain signals.”

According to Dr. Singh, there’s little data about seizures in patients with COVID-19 because doctors have focused on other symptoms. A 2021 multicenter study found that electrographic seizures were detected in 9.6% of 197 patients with COVID-19 who were referred for cEEG.

For the new study, Dr. Singh and a colleague tracked 917 patients with COVID-19 in the Northwell Health system who were treated from Feb. 14 to June 14, 2020, with antiepileptic medication. Of the patients, 451 had a history of epilepsy, and 466 did not.

According to Dr. Singh, 27.6% of the patients without a history of epilepsy had new-onset seizures, while 10.1% of the patients with history of epilepsy had breakthrough seizures. The difference in odds was more than threefold after adjustment. (Among all COVID-19 patients, he said, perhaps 8%-16% had seizures).

The researchers also found that patients with new-onset seizures stayed in the hospital much longer (average, 26.9 days) than any patients with a known history of epilepsy (12.8 days, P < .0001, for those who had breakthrough seizures and 10.9 days, P < .0001, for those who didn’t).

In addition, the researchers found that having any seizures – new-onset or breakthrough – was linked to higher risk of death (OR 1.41, P = .03).

Antiseizure medications are key treatments for these patients, Dr. Singh said. As for the patients with new-onset seizures who recover from COVID-19, Dr. Singh said, “it’s suspected that these people are going to have a new diagnosis of epilepsy, not just a one-time seizure.”

The findings suggest that some patients with epilepsy are protected against COVID-19-related seizures because they take antiepileptic medications that “protect the brain from getting a trigger for an abnormal signal that leads to a seizure,” he said. “That’s one possibility.”

What can neurologists learn from the study? Dr. Singh recommends a “lower threshold” to recommend or approve EEGs in patients with COVID-19 who are confused/altered when they come in, especially if this is not normal. “They may actually be having silent seizures that no one’s noticing,” he said.

No study funding was reported. The authors reported no relevant disclosures.

An analysis of hospitalized patients with COVID-19 finds that those with no history of epilepsy had more than 3 times the odds of suffering a new-onset seizure than patients with epilepsy were to have breakthrough seizures (odds radio [OR] 3.15, P < .0001), researchers reported at the annual meeting of the American Epilepsy Society.

“If you have COVID and you have a seizure, it’s more likely that you’re having it for the first time, and it’s not as likely that you have epilepsy,” study lead author Neeraj Singh, MD, a neurologist at the New York-based Northwell Health system, said in an interview. “That’s new. We don’t normally see that when someone has a bacterial or viral infection. It’s demonstrating that this infection is having direct effect on the brain and brain signals.”

According to Dr. Singh, there’s little data about seizures in patients with COVID-19 because doctors have focused on other symptoms. A 2021 multicenter study found that electrographic seizures were detected in 9.6% of 197 patients with COVID-19 who were referred for cEEG.

For the new study, Dr. Singh and a colleague tracked 917 patients with COVID-19 in the Northwell Health system who were treated from Feb. 14 to June 14, 2020, with antiepileptic medication. Of the patients, 451 had a history of epilepsy, and 466 did not.

According to Dr. Singh, 27.6% of the patients without a history of epilepsy had new-onset seizures, while 10.1% of the patients with history of epilepsy had breakthrough seizures. The difference in odds was more than threefold after adjustment. (Among all COVID-19 patients, he said, perhaps 8%-16% had seizures).

The researchers also found that patients with new-onset seizures stayed in the hospital much longer (average, 26.9 days) than any patients with a known history of epilepsy (12.8 days, P < .0001, for those who had breakthrough seizures and 10.9 days, P < .0001, for those who didn’t).

In addition, the researchers found that having any seizures – new-onset or breakthrough – was linked to higher risk of death (OR 1.41, P = .03).

Antiseizure medications are key treatments for these patients, Dr. Singh said. As for the patients with new-onset seizures who recover from COVID-19, Dr. Singh said, “it’s suspected that these people are going to have a new diagnosis of epilepsy, not just a one-time seizure.”

The findings suggest that some patients with epilepsy are protected against COVID-19-related seizures because they take antiepileptic medications that “protect the brain from getting a trigger for an abnormal signal that leads to a seizure,” he said. “That’s one possibility.”

What can neurologists learn from the study? Dr. Singh recommends a “lower threshold” to recommend or approve EEGs in patients with COVID-19 who are confused/altered when they come in, especially if this is not normal. “They may actually be having silent seizures that no one’s noticing,” he said.

No study funding was reported. The authors reported no relevant disclosures.

An analysis of hospitalized patients with COVID-19 finds that those with no history of epilepsy had more than 3 times the odds of suffering a new-onset seizure than patients with epilepsy were to have breakthrough seizures (odds radio [OR] 3.15, P < .0001), researchers reported at the annual meeting of the American Epilepsy Society.

“If you have COVID and you have a seizure, it’s more likely that you’re having it for the first time, and it’s not as likely that you have epilepsy,” study lead author Neeraj Singh, MD, a neurologist at the New York-based Northwell Health system, said in an interview. “That’s new. We don’t normally see that when someone has a bacterial or viral infection. It’s demonstrating that this infection is having direct effect on the brain and brain signals.”

According to Dr. Singh, there’s little data about seizures in patients with COVID-19 because doctors have focused on other symptoms. A 2021 multicenter study found that electrographic seizures were detected in 9.6% of 197 patients with COVID-19 who were referred for cEEG.

For the new study, Dr. Singh and a colleague tracked 917 patients with COVID-19 in the Northwell Health system who were treated from Feb. 14 to June 14, 2020, with antiepileptic medication. Of the patients, 451 had a history of epilepsy, and 466 did not.

According to Dr. Singh, 27.6% of the patients without a history of epilepsy had new-onset seizures, while 10.1% of the patients with history of epilepsy had breakthrough seizures. The difference in odds was more than threefold after adjustment. (Among all COVID-19 patients, he said, perhaps 8%-16% had seizures).

The researchers also found that patients with new-onset seizures stayed in the hospital much longer (average, 26.9 days) than any patients with a known history of epilepsy (12.8 days, P < .0001, for those who had breakthrough seizures and 10.9 days, P < .0001, for those who didn’t).

In addition, the researchers found that having any seizures – new-onset or breakthrough – was linked to higher risk of death (OR 1.41, P = .03).

Antiseizure medications are key treatments for these patients, Dr. Singh said. As for the patients with new-onset seizures who recover from COVID-19, Dr. Singh said, “it’s suspected that these people are going to have a new diagnosis of epilepsy, not just a one-time seizure.”

The findings suggest that some patients with epilepsy are protected against COVID-19-related seizures because they take antiepileptic medications that “protect the brain from getting a trigger for an abnormal signal that leads to a seizure,” he said. “That’s one possibility.”

What can neurologists learn from the study? Dr. Singh recommends a “lower threshold” to recommend or approve EEGs in patients with COVID-19 who are confused/altered when they come in, especially if this is not normal. “They may actually be having silent seizures that no one’s noticing,” he said.

No study funding was reported. The authors reported no relevant disclosures.

No one’s quite sure what causes uveal melanoma (UM). Unlike skin cancers, UM doesn’t seem to have any link to exposure to ultraviolet rays, although it’s most likely to strike people who are vulnerable to sun damage, like Caucasians and people with lighter eyes and lighter skin (but not lighter hair), and an inability to tan. Up to half of those affected by the disease will recover after treatment. In the other half, the cancer spreads from the eye – typically to the liver – and patient prognoses remain extremely poor despite extensive efforts to develop effective treatments.

“The median survival is probably about 2 years, and there are a number of papers out there that talk about life expectancy as short as 6 months,” said Marlana Orloff, MD, an associate professor of medical oncology at Thomas Jefferson University Hospital, Philadelphia.

But there is hope on the horizon, even if it’s not as near as patients would prefer. “Just over the last 5-10 years, we’ve gained a lot more knowledge about this disease as we try to understand how distinctly different it is, how mutations drive it, and how we can approach it using immunotherapy,” Dr. Orloff said. “I hope we’ll come up with better options for prolonging survival.” Indeed, multiple clinical trials are in the works despite the rarity of the disease.

Tracking uveal melanoma’s dangerous course

All melanomas, including UM, strike the melanocytes (cells) that provide pigment. According to a 2017 report¹ in the journal Eye, “uveal melanoma is the most common primary intraocular tumor in adults with a mean age-adjusted incidence of 5.1 cases per million per year. Tumors are located either in the iris (4%), ciliary body (6%), or choroid (90%) . … As in many other cancer indications, both early detection and early treatment could be critical for a positive long-term survival outcome in uveal melanoma.”

The median age of diagnosis is 59-62 years, the report says, although non-Whites seem to develop the disease earlier.

The vast majority of patients receive treatment by plaque brachytherapy via radioactive seeds. “It’s like brachytherapy of the prostate,” said medical oncologist Rino S. Seedor, MD, of Thomas Jefferson University Hospital. “If the eye tumor is too big or invasive, they’ll cut out the eye.”

As many as 50% of patients will develop metastasis, sometimes within 2-3 years in those who have large tumors and high genetic risk, said ophthalmologist and radiation oncologist Miguel Materin, MD, of Duke University Eye Center, Durham, N.C. “There’s probably micrometastasis early in the development of the tumor,” he said. “The metastasis might develop before we or the patient knows there’s a tumor.”

Some physicians question the value of prognostic testing in patients who don’t yet show signs of metastasis, Dr. Materin said, because the findings can be grim.

Unlike his more cautious colleagues, Dr. Materin prefers to pursue testing, he said. Most patients agree to it. “It’s up to them to decide if they want to know if they have a bad prognosis,” he said, and the findings can be helpful to physicians because they provide useful genetic information about tumors.

Monitoring for liver metastasis is key

UM metastases are most likely to strike the liver, and prognoses are especially poor when they do. According to a 2019 analysis of 175 patients with metastatic UM in the Netherlands, “the presence of liver metastases is negatively associated with survival (hazard ratio = 2.09; 95% confidence interval, 1.07-4.08). … In 154 (88%) patients, the liver was affected, and only 3 patients were reported to have brain metastases.”²

As a result, physicians recommend close monitoring in patients with UM. Thomas Jefferson University’s Dr. Orloff uses tumor stages and genetic risk profiles to guide surveillance. “Very large tumors and/or monosomy 3 and 8q amplification or a Class 2 gene signature would suggest a higher-risk tumor,” she said. “For these patients we recommend MRI of the abdomen every 3 months for 2 years, CT of the chest every 6 months for 2 years, labs every 3 months for 2 years, then MRI every 6 months until year 5 with chest imaging yearly, then at 5 years everything yearly. For lower- or intermediate-risk patients we recommend MRI of the abdomen every 6 months for 5 years, chest imaging yearly, labs every 6 months, then at 5 years everything yearly.”

In the United States, patients with metastatic disease are typically sent to referral centers at institutions such as Duke, Yale (New Haven, Conn.), and Thomas Jefferson universities.

Metastasis treatments offer limited relief

There are no FDA-approved treatments for metastatic MU, and the treatments that physicians do use don’t seem to have much of an effect on life span. A 2019 study examined 73 patients with MU metastasis to the liver who were treated from 2004 to 2011 and 2012 to 2016. Among both cohorts, those who had no treatment lived nearly as long (median of 15 months) as those treated with local therapy (median of 18.7 months). Median survival for the entire population was 15 months (95% CI: 11–18 months). There was no statistically significant difference between the periods.³

However, there are signs that a move away from first-line chemotherapy in recent decades has led to longer life spans. Dr. Seedor led a 2018 study⁴ that compared two cohorts of MU patients with liver metastasis at her university: 98 patients from 1971 to 1993 (81% received systemic chemotherapy as their initial therapy) and 574 from 2000 to 2017 (they received various liver-directed initial treatments such as chemoembolization, drug-eluting beads, immunoembolization, and radioembolization).

The patients in the second group lived longer after treatment of initial UM than the first group (5.1 years vs. 3.3 years, P < .001) and after the development of liver metastasis (16.4 months vs. 4.8 months, P < .001). A 2020 follow-up study reported similar findings and noted that a “combination of liver-directed and newly developed systemic treatments may further improve the survival of these patients.”⁵

At Thomas Jefferson Medical Center, liver-directed therapy includes radioembolization, chemomobilization, and microwave ablation, Dr. Seedor said. “Which one we choose is based on how big the tumors are.”

Treatments in development could make advances

Physicians are working on several fronts to develop new treatments. A 2021 review of clinical trials found numerous trials regarding checkpoint inhibition, one devoted to a vaccine, and several involving checkpoint inhibitors. The review author notes that “the low mutational burden and poor immunogenicity of UM tumors may underlie poor responses and resistance to [immune checkpoint inhibitors] alone.”⁶

Earlier this year, grant-funded researchers reported encouraging news on the G protein inhibitor front. Their study found that FR900359, a selective inhibitor of the Gq/11/14 subfamily of heterotrimeric G proteins, could hold promise for “treating UM and potentially other diseases caused by constitutively active Gq/11.”⁷

In another 2021 study, this one with no reported funding, researchers explored the tumor microenvironment of UM and reported that their findings “provided a robust gene-based prognostic signature for predicting prognosis of UM patients and proposed a potential targeted therapy for preventing UM metastasis.”⁸

Experimental drug may add months of life

Physicians often recommend that patients take part in clinical trials. Earlier this year, researchers reported that a drug called tebentafusp – a bispecific fusion protein – slightly boosted metastatic UM survival in an open-label, phase 3 clinical trial when used as a first-line treatment. Patients were randomly assigned to tebentafusp, 1 of 2 immunotherapy drugs (ipilimumab or pembrolizumab), or the chemotherapy drug dacarbazine. Those who took tebentafusp vs. the other options lived longer with an estimated 1-year overall rate of 73.2% (95% CI: 66.3-78.9) vs. 57.5% (95% CI: 47.0-66.6), respectively. Fewer than 4% of those on tebentafusp needed to stop it because of adverse effects, and no treatment-related deaths occurred.⁹

Dr. Orloff is one of the coauthors of this study.

The National Cancer Institute provided more details about the industry-funded research and noted that median overall survival for patients who received the drug was 21.7 months vs. 16 months for the control group.

Not every patient is eligible for this treatment, however. A coauthor told the American Association for Cancer Research that “the major limitation of tebentafusp is that it can only be used in patients who have a specific HLA [human leukocyte antigen] type.” Patients must be HLA-A*0201-positive.¹⁰

In August 2021, the FDA granted priority review for tebentafusp.¹¹ And in September 2021, a company called TriSalus announced the first patient enrollment in a “clinical study evaluating the administration of SD-101, an investigational toll-like receptor 9 (TLR9) agonist in adults with metastatic uveal melanoma.”¹²

According to the company, the research “is designed to evaluate the intravascular administration of SD-101 into uveal melanoma liver metastasis lesions in combination with checkpoint inhibitors using the novel Pressure-Enabled Drug Delivery (PEDD) approach.” This strategy is “designed to overcome the inherent intratumoral pressure of solid tumors,” the company said.

Dr. Materin serves on a scientific advisory board for Castle Biosciences. Dr. Orloff is a consultant for Immunocore, which funded the tebentafusp study, and serves on a scientific advisory board for TriSalus. Dr. Seedor reports no disclosures.

References

1.Kaliki S and Shields C. Eye. 2017 Feb;31:241-57.

2.Jochems A et al. Cancers. 2019 July;11(7):1007.

3.Xu LT et al. Ocul Oncol Pathol. 2019;5:323-32.

4.Seedor RS et al. J Clin Oncol. 2018 May;36(15_suppl):9592.

5.Seedor RS et al. Cancers (Basel). 2020 Jan 1;12(1):117.

6.Orloff M. Ocul Oncol Pathol. 2021 July;7:168-76.

7.Onken MD et al. J Biol Chem. 2021;296:100403.

8.Lei S and Zhang Y. Int Immunopharmacol. 2021 July;96:107816.

9.Piperno-Neumann S et al. Proceedings of the 112th Annual Meeting of the American Association for Cancer Research; 2021 April 10-15. Philadelphia (Pa.): AACR; 2021. Abstract nr 5133.

10.National Cancer Institute: https://www.cancer.gov/news-events/cancer-currents-blog/2021/tebentafusp-uveal-melanoma-improves-survival

11.Immunocore press release: https://ir.immunocore.com/news-releases/news-release-details/immunocore-announces-us-food-and-drug-administration-and

12.Trisalus announcement: https://finance.yahoo.com/news/trisalus-life-sciences-announces-first-130000215.html?guccounter=1

No one’s quite sure what causes uveal melanoma (UM). Unlike skin cancers, UM doesn’t seem to have any link to exposure to ultraviolet rays, although it’s most likely to strike people who are vulnerable to sun damage, like Caucasians and people with lighter eyes and lighter skin (but not lighter hair), and an inability to tan. Up to half of those affected by the disease will recover after treatment. In the other half, the cancer spreads from the eye – typically to the liver – and patient prognoses remain extremely poor despite extensive efforts to develop effective treatments.

“The median survival is probably about 2 years, and there are a number of papers out there that talk about life expectancy as short as 6 months,” said Marlana Orloff, MD, an associate professor of medical oncology at Thomas Jefferson University Hospital, Philadelphia.

But there is hope on the horizon, even if it’s not as near as patients would prefer. “Just over the last 5-10 years, we’ve gained a lot more knowledge about this disease as we try to understand how distinctly different it is, how mutations drive it, and how we can approach it using immunotherapy,” Dr. Orloff said. “I hope we’ll come up with better options for prolonging survival.” Indeed, multiple clinical trials are in the works despite the rarity of the disease.

Tracking uveal melanoma’s dangerous course

All melanomas, including UM, strike the melanocytes (cells) that provide pigment. According to a 2017 report¹ in the journal Eye, “uveal melanoma is the most common primary intraocular tumor in adults with a mean age-adjusted incidence of 5.1 cases per million per year. Tumors are located either in the iris (4%), ciliary body (6%), or choroid (90%) . … As in many other cancer indications, both early detection and early treatment could be critical for a positive long-term survival outcome in uveal melanoma.”

The median age of diagnosis is 59-62 years, the report says, although non-Whites seem to develop the disease earlier.

The vast majority of patients receive treatment by plaque brachytherapy via radioactive seeds. “It’s like brachytherapy of the prostate,” said medical oncologist Rino S. Seedor, MD, of Thomas Jefferson University Hospital. “If the eye tumor is too big or invasive, they’ll cut out the eye.”

As many as 50% of patients will develop metastasis, sometimes within 2-3 years in those who have large tumors and high genetic risk, said ophthalmologist and radiation oncologist Miguel Materin, MD, of Duke University Eye Center, Durham, N.C. “There’s probably micrometastasis early in the development of the tumor,” he said. “The metastasis might develop before we or the patient knows there’s a tumor.”

Some physicians question the value of prognostic testing in patients who don’t yet show signs of metastasis, Dr. Materin said, because the findings can be grim.

Unlike his more cautious colleagues, Dr. Materin prefers to pursue testing, he said. Most patients agree to it. “It’s up to them to decide if they want to know if they have a bad prognosis,” he said, and the findings can be helpful to physicians because they provide useful genetic information about tumors.

Monitoring for liver metastasis is key

UM metastases are most likely to strike the liver, and prognoses are especially poor when they do. According to a 2019 analysis of 175 patients with metastatic UM in the Netherlands, “the presence of liver metastases is negatively associated with survival (hazard ratio = 2.09; 95% confidence interval, 1.07-4.08). … In 154 (88%) patients, the liver was affected, and only 3 patients were reported to have brain metastases.”²

As a result, physicians recommend close monitoring in patients with UM. Thomas Jefferson University’s Dr. Orloff uses tumor stages and genetic risk profiles to guide surveillance. “Very large tumors and/or monosomy 3 and 8q amplification or a Class 2 gene signature would suggest a higher-risk tumor,” she said. “For these patients we recommend MRI of the abdomen every 3 months for 2 years, CT of the chest every 6 months for 2 years, labs every 3 months for 2 years, then MRI every 6 months until year 5 with chest imaging yearly, then at 5 years everything yearly. For lower- or intermediate-risk patients we recommend MRI of the abdomen every 6 months for 5 years, chest imaging yearly, labs every 6 months, then at 5 years everything yearly.”

In the United States, patients with metastatic disease are typically sent to referral centers at institutions such as Duke, Yale (New Haven, Conn.), and Thomas Jefferson universities.

Metastasis treatments offer limited relief

There are no FDA-approved treatments for metastatic MU, and the treatments that physicians do use don’t seem to have much of an effect on life span. A 2019 study examined 73 patients with MU metastasis to the liver who were treated from 2004 to 2011 and 2012 to 2016. Among both cohorts, those who had no treatment lived nearly as long (median of 15 months) as those treated with local therapy (median of 18.7 months). Median survival for the entire population was 15 months (95% CI: 11–18 months). There was no statistically significant difference between the periods.³

However, there are signs that a move away from first-line chemotherapy in recent decades has led to longer life spans. Dr. Seedor led a 2018 study⁴ that compared two cohorts of MU patients with liver metastasis at her university: 98 patients from 1971 to 1993 (81% received systemic chemotherapy as their initial therapy) and 574 from 2000 to 2017 (they received various liver-directed initial treatments such as chemoembolization, drug-eluting beads, immunoembolization, and radioembolization).

The patients in the second group lived longer after treatment of initial UM than the first group (5.1 years vs. 3.3 years, P < .001) and after the development of liver metastasis (16.4 months vs. 4.8 months, P < .001). A 2020 follow-up study reported similar findings and noted that a “combination of liver-directed and newly developed systemic treatments may further improve the survival of these patients.”⁵

At Thomas Jefferson Medical Center, liver-directed therapy includes radioembolization, chemomobilization, and microwave ablation, Dr. Seedor said. “Which one we choose is based on how big the tumors are.”

Treatments in development could make advances

Physicians are working on several fronts to develop new treatments. A 2021 review of clinical trials found numerous trials regarding checkpoint inhibition, one devoted to a vaccine, and several involving checkpoint inhibitors. The review author notes that “the low mutational burden and poor immunogenicity of UM tumors may underlie poor responses and resistance to [immune checkpoint inhibitors] alone.”⁶

Earlier this year, grant-funded researchers reported encouraging news on the G protein inhibitor front. Their study found that FR900359, a selective inhibitor of the Gq/11/14 subfamily of heterotrimeric G proteins, could hold promise for “treating UM and potentially other diseases caused by constitutively active Gq/11.”⁷

In another 2021 study, this one with no reported funding, researchers explored the tumor microenvironment of UM and reported that their findings “provided a robust gene-based prognostic signature for predicting prognosis of UM patients and proposed a potential targeted therapy for preventing UM metastasis.”⁸

Experimental drug may add months of life

Physicians often recommend that patients take part in clinical trials. Earlier this year, researchers reported that a drug called tebentafusp – a bispecific fusion protein – slightly boosted metastatic UM survival in an open-label, phase 3 clinical trial when used as a first-line treatment. Patients were randomly assigned to tebentafusp, 1 of 2 immunotherapy drugs (ipilimumab or pembrolizumab), or the chemotherapy drug dacarbazine. Those who took tebentafusp vs. the other options lived longer with an estimated 1-year overall rate of 73.2% (95% CI: 66.3-78.9) vs. 57.5% (95% CI: 47.0-66.6), respectively. Fewer than 4% of those on tebentafusp needed to stop it because of adverse effects, and no treatment-related deaths occurred.⁹

Dr. Orloff is one of the coauthors of this study.

The National Cancer Institute provided more details about the industry-funded research and noted that median overall survival for patients who received the drug was 21.7 months vs. 16 months for the control group.

Not every patient is eligible for this treatment, however. A coauthor told the American Association for Cancer Research that “the major limitation of tebentafusp is that it can only be used in patients who have a specific HLA [human leukocyte antigen] type.” Patients must be HLA-A*0201-positive.¹⁰

In August 2021, the FDA granted priority review for tebentafusp.¹¹ And in September 2021, a company called TriSalus announced the first patient enrollment in a “clinical study evaluating the administration of SD-101, an investigational toll-like receptor 9 (TLR9) agonist in adults with metastatic uveal melanoma.”¹²

According to the company, the research “is designed to evaluate the intravascular administration of SD-101 into uveal melanoma liver metastasis lesions in combination with checkpoint inhibitors using the novel Pressure-Enabled Drug Delivery (PEDD) approach.” This strategy is “designed to overcome the inherent intratumoral pressure of solid tumors,” the company said.

Dr. Materin serves on a scientific advisory board for Castle Biosciences. Dr. Orloff is a consultant for Immunocore, which funded the tebentafusp study, and serves on a scientific advisory board for TriSalus. Dr. Seedor reports no disclosures.

References

1.Kaliki S and Shields C. Eye. 2017 Feb;31:241-57.

2.Jochems A et al. Cancers. 2019 July;11(7):1007.

3.Xu LT et al. Ocul Oncol Pathol. 2019;5:323-32.

4.Seedor RS et al. J Clin Oncol. 2018 May;36(15_suppl):9592.

5.Seedor RS et al. Cancers (Basel). 2020 Jan 1;12(1):117.

6.Orloff M. Ocul Oncol Pathol. 2021 July;7:168-76.

7.Onken MD et al. J Biol Chem. 2021;296:100403.

8.Lei S and Zhang Y. Int Immunopharmacol. 2021 July;96:107816.

9.Piperno-Neumann S et al. Proceedings of the 112th Annual Meeting of the American Association for Cancer Research; 2021 April 10-15. Philadelphia (Pa.): AACR; 2021. Abstract nr 5133.

10.National Cancer Institute: https://www.cancer.gov/news-events/cancer-currents-blog/2021/tebentafusp-uveal-melanoma-improves-survival

11.Immunocore press release: https://ir.immunocore.com/news-releases/news-release-details/immunocore-announces-us-food-and-drug-administration-and

12.Trisalus announcement: https://finance.yahoo.com/news/trisalus-life-sciences-announces-first-130000215.html?guccounter=1

No one’s quite sure what causes uveal melanoma (UM). Unlike skin cancers, UM doesn’t seem to have any link to exposure to ultraviolet rays, although it’s most likely to strike people who are vulnerable to sun damage, like Caucasians and people with lighter eyes and lighter skin (but not lighter hair), and an inability to tan. Up to half of those affected by the disease will recover after treatment. In the other half, the cancer spreads from the eye – typically to the liver – and patient prognoses remain extremely poor despite extensive efforts to develop effective treatments.

“The median survival is probably about 2 years, and there are a number of papers out there that talk about life expectancy as short as 6 months,” said Marlana Orloff, MD, an associate professor of medical oncology at Thomas Jefferson University Hospital, Philadelphia.

But there is hope on the horizon, even if it’s not as near as patients would prefer. “Just over the last 5-10 years, we’ve gained a lot more knowledge about this disease as we try to understand how distinctly different it is, how mutations drive it, and how we can approach it using immunotherapy,” Dr. Orloff said. “I hope we’ll come up with better options for prolonging survival.” Indeed, multiple clinical trials are in the works despite the rarity of the disease.

Tracking uveal melanoma’s dangerous course

All melanomas, including UM, strike the melanocytes (cells) that provide pigment. According to a 2017 report¹ in the journal Eye, “uveal melanoma is the most common primary intraocular tumor in adults with a mean age-adjusted incidence of 5.1 cases per million per year. Tumors are located either in the iris (4%), ciliary body (6%), or choroid (90%) . … As in many other cancer indications, both early detection and early treatment could be critical for a positive long-term survival outcome in uveal melanoma.”

The median age of diagnosis is 59-62 years, the report says, although non-Whites seem to develop the disease earlier.

The vast majority of patients receive treatment by plaque brachytherapy via radioactive seeds. “It’s like brachytherapy of the prostate,” said medical oncologist Rino S. Seedor, MD, of Thomas Jefferson University Hospital. “If the eye tumor is too big or invasive, they’ll cut out the eye.”

As many as 50% of patients will develop metastasis, sometimes within 2-3 years in those who have large tumors and high genetic risk, said ophthalmologist and radiation oncologist Miguel Materin, MD, of Duke University Eye Center, Durham, N.C. “There’s probably micrometastasis early in the development of the tumor,” he said. “The metastasis might develop before we or the patient knows there’s a tumor.”

Some physicians question the value of prognostic testing in patients who don’t yet show signs of metastasis, Dr. Materin said, because the findings can be grim.

Unlike his more cautious colleagues, Dr. Materin prefers to pursue testing, he said. Most patients agree to it. “It’s up to them to decide if they want to know if they have a bad prognosis,” he said, and the findings can be helpful to physicians because they provide useful genetic information about tumors.

Monitoring for liver metastasis is key

UM metastases are most likely to strike the liver, and prognoses are especially poor when they do. According to a 2019 analysis of 175 patients with metastatic UM in the Netherlands, “the presence of liver metastases is negatively associated with survival (hazard ratio = 2.09; 95% confidence interval, 1.07-4.08). … In 154 (88%) patients, the liver was affected, and only 3 patients were reported to have brain metastases.”²

As a result, physicians recommend close monitoring in patients with UM. Thomas Jefferson University’s Dr. Orloff uses tumor stages and genetic risk profiles to guide surveillance. “Very large tumors and/or monosomy 3 and 8q amplification or a Class 2 gene signature would suggest a higher-risk tumor,” she said. “For these patients we recommend MRI of the abdomen every 3 months for 2 years, CT of the chest every 6 months for 2 years, labs every 3 months for 2 years, then MRI every 6 months until year 5 with chest imaging yearly, then at 5 years everything yearly. For lower- or intermediate-risk patients we recommend MRI of the abdomen every 6 months for 5 years, chest imaging yearly, labs every 6 months, then at 5 years everything yearly.”

In the United States, patients with metastatic disease are typically sent to referral centers at institutions such as Duke, Yale (New Haven, Conn.), and Thomas Jefferson universities.

Metastasis treatments offer limited relief

There are no FDA-approved treatments for metastatic MU, and the treatments that physicians do use don’t seem to have much of an effect on life span. A 2019 study examined 73 patients with MU metastasis to the liver who were treated from 2004 to 2011 and 2012 to 2016. Among both cohorts, those who had no treatment lived nearly as long (median of 15 months) as those treated with local therapy (median of 18.7 months). Median survival for the entire population was 15 months (95% CI: 11–18 months). There was no statistically significant difference between the periods.³

However, there are signs that a move away from first-line chemotherapy in recent decades has led to longer life spans. Dr. Seedor led a 2018 study⁴ that compared two cohorts of MU patients with liver metastasis at her university: 98 patients from 1971 to 1993 (81% received systemic chemotherapy as their initial therapy) and 574 from 2000 to 2017 (they received various liver-directed initial treatments such as chemoembolization, drug-eluting beads, immunoembolization, and radioembolization).

The patients in the second group lived longer after treatment of initial UM than the first group (5.1 years vs. 3.3 years, P < .001) and after the development of liver metastasis (16.4 months vs. 4.8 months, P < .001). A 2020 follow-up study reported similar findings and noted that a “combination of liver-directed and newly developed systemic treatments may further improve the survival of these patients.”⁵

At Thomas Jefferson Medical Center, liver-directed therapy includes radioembolization, chemomobilization, and microwave ablation, Dr. Seedor said. “Which one we choose is based on how big the tumors are.”

Treatments in development could make advances

Physicians are working on several fronts to develop new treatments. A 2021 review of clinical trials found numerous trials regarding checkpoint inhibition, one devoted to a vaccine, and several involving checkpoint inhibitors. The review author notes that “the low mutational burden and poor immunogenicity of UM tumors may underlie poor responses and resistance to [immune checkpoint inhibitors] alone.”⁶

Earlier this year, grant-funded researchers reported encouraging news on the G protein inhibitor front. Their study found that FR900359, a selective inhibitor of the Gq/11/14 subfamily of heterotrimeric G proteins, could hold promise for “treating UM and potentially other diseases caused by constitutively active Gq/11.”⁷

In another 2021 study, this one with no reported funding, researchers explored the tumor microenvironment of UM and reported that their findings “provided a robust gene-based prognostic signature for predicting prognosis of UM patients and proposed a potential targeted therapy for preventing UM metastasis.”⁸

Experimental drug may add months of life

Physicians often recommend that patients take part in clinical trials. Earlier this year, researchers reported that a drug called tebentafusp – a bispecific fusion protein – slightly boosted metastatic UM survival in an open-label, phase 3 clinical trial when used as a first-line treatment. Patients were randomly assigned to tebentafusp, 1 of 2 immunotherapy drugs (ipilimumab or pembrolizumab), or the chemotherapy drug dacarbazine. Those who took tebentafusp vs. the other options lived longer with an estimated 1-year overall rate of 73.2% (95% CI: 66.3-78.9) vs. 57.5% (95% CI: 47.0-66.6), respectively. Fewer than 4% of those on tebentafusp needed to stop it because of adverse effects, and no treatment-related deaths occurred.⁹

Dr. Orloff is one of the coauthors of this study.

The National Cancer Institute provided more details about the industry-funded research and noted that median overall survival for patients who received the drug was 21.7 months vs. 16 months for the control group.

Not every patient is eligible for this treatment, however. A coauthor told the American Association for Cancer Research that “the major limitation of tebentafusp is that it can only be used in patients who have a specific HLA [human leukocyte antigen] type.” Patients must be HLA-A*0201-positive.¹⁰

In August 2021, the FDA granted priority review for tebentafusp.¹¹ And in September 2021, a company called TriSalus announced the first patient enrollment in a “clinical study evaluating the administration of SD-101, an investigational toll-like receptor 9 (TLR9) agonist in adults with metastatic uveal melanoma.”¹²

According to the company, the research “is designed to evaluate the intravascular administration of SD-101 into uveal melanoma liver metastasis lesions in combination with checkpoint inhibitors using the novel Pressure-Enabled Drug Delivery (PEDD) approach.” This strategy is “designed to overcome the inherent intratumoral pressure of solid tumors,” the company said.

Dr. Materin serves on a scientific advisory board for Castle Biosciences. Dr. Orloff is a consultant for Immunocore, which funded the tebentafusp study, and serves on a scientific advisory board for TriSalus. Dr. Seedor reports no disclosures.

References

1.Kaliki S and Shields C. Eye. 2017 Feb;31:241-57.

2.Jochems A et al. Cancers. 2019 July;11(7):1007.

3.Xu LT et al. Ocul Oncol Pathol. 2019;5:323-32.

4.Seedor RS et al. J Clin Oncol. 2018 May;36(15_suppl):9592.

5.Seedor RS et al. Cancers (Basel). 2020 Jan 1;12(1):117.

6.Orloff M. Ocul Oncol Pathol. 2021 July;7:168-76.

7.Onken MD et al. J Biol Chem. 2021;296:100403.

8.Lei S and Zhang Y. Int Immunopharmacol. 2021 July;96:107816.

9.Piperno-Neumann S et al. Proceedings of the 112th Annual Meeting of the American Association for Cancer Research; 2021 April 10-15. Philadelphia (Pa.): AACR; 2021. Abstract nr 5133.

10.National Cancer Institute: https://www.cancer.gov/news-events/cancer-currents-blog/2021/tebentafusp-uveal-melanoma-improves-survival

11.Immunocore press release: https://ir.immunocore.com/news-releases/news-release-details/immunocore-announces-us-food-and-drug-administration-and

12.Trisalus announcement: https://finance.yahoo.com/news/trisalus-life-sciences-announces-first-130000215.html?guccounter=1