The painful paused and repaused rollout of the new Cerner electronic health record (EHR) system at the US Department of Veterans Affairs (VA) is now halted as the VA announces a “reset.” The decision applies to all planned deployments. An exception is the Captain James A. Lovell Federal Health Care Center in Chicago, the only fully integrated VA and US Department of Defense (DoD) health care system, which is expected go live in March 2024 as planned. The DoD rollout of its Cerner EHR is further along and expected to be completed in 2024.

The new plan is to redirect resources and “prioritize improvements” at the 5 sites currently using the new EHR: Spokane VA Health Care System, VA Walla Walla Health Care, Roseburg VA Health Care System, VA Southern Oregon Health Care, and VA Central Ohio Health Care System. Additional deployments will not be scheduled, the VA says, until it is confident that the new EHR is highly functioning at the current sites and ready to deliver at future sites, as demonstrated by “clear improvements” in the clinician and veteran experience, sustained high performance and high reliability.

“For the past few years, we’ve tried to fix this plane while flying it—and that hasn’t delivered the results that veterans or our staff deserve,” said Neil Evans, MD, acting program executive director at the Electronic Health Record Modernization Integration Office. “This reset changes that. We are going to take the time necessary to get this right for veterans and VA clinicians alike, and that means focusing our resources solely on improving the EHR at the sites where it is currently in use, and improving its fit for VA more broadly. In doing so, we will enhance the EHR for both current and future users, paving the way for successful future deployments.”  

The various EHR rollouts around the country have been bumpy from the beginning, operating by fits and starts as new problems surfaced and were addressed. To be fair, the whole implementation process only started in 2020 (and deployed at the first VA hospital during the COVID-19 pandemic), but in that time, the VA has had to, in its own words, “revise the timeline” again and again. The Boise VA Medical Center, for instance, was originally scheduled to go live June 25, 2022, then a month later—then 2023.

The VA Office of the Inspector General published 3 reports last year that found significant issues, including improperly routed clinical orders. VA Secretary Denis McDonough announced last July that the VA would delay EHR deployments until January 2023 to ensure that the system’s issues had been resolved. “During VA’s subsequent investigation at our current sites,” he said, “several additional technical and system issues were identified—including challenges with performance, such as latency and slowness, problems with patient scheduling, referrals, medication management, and other types of medical orders.”

In February, Ken Glueck, executive vice president of Oracle, wrote a blog post that was both apologia and explanation. Modernization, he said, “doesn’t come with a magic wand and there’s no easy button.”

After the DoD moved to Cerner for a new EHR system, the VA decided to follow suit. The goal was to create a “seamless, longitudinal record”—and that was the beginning of the largest health IT modernization project in history, Glueck said. And, although he didn’t mention it, the beginning of one of the VA’s biggest headaches. The problem, Glueck wrote, was that the new project involved “standardizing procedures and workflows that may have been different across 130 VistA implementations at largely autonomous VA medical centers.”

In June 2022—a significant month in the whole rollout process—Cerner was acquired by Oracle. By Glueck’s lights, that meant the VA “now has essentially 2 vendors for the price of one—one with extensive clinical expertise and one with extensive engineering expertise.”

Oracle, he said, “is hard at work to stabilize and improve performance; make fixes to functionality and design issues; improve training and build a better user experience.” He noted that significant improvements to the system’s capacity and performance have included reducing the most severe outage incidents by 67%.

In a recent statement, House VA Committee Chairman Mike Bost (R-IL) and Technology Modernization Subcommittee Chairman Matt Rosendale (R-MT) said, “We support Secretary McDonough’s decision in the strongest possible terms. The best way to get out of a hole is to stop digging, and we’re encouraged that VA and Oracle Cerner have finally realized that.”

VA and Oracle Cerner are currently working toward an amended contract that will "increase Oracle Cerner’s accountability to deliver a high-functioning, high-reliability, world-class EHR system,” the VA says. As part of the re-set, the VA also will work with Congress on resource requirements. The VA estimates FY 2023 costs will be reduced by $400 million. 

The painful paused and repaused rollout of the new Cerner electronic health record (EHR) system at the US Department of Veterans Affairs (VA) is now halted as the VA announces a “reset.” The decision applies to all planned deployments. An exception is the Captain James A. Lovell Federal Health Care Center in Chicago, the only fully integrated VA and US Department of Defense (DoD) health care system, which is expected go live in March 2024 as planned. The DoD rollout of its Cerner EHR is further along and expected to be completed in 2024.

The new plan is to redirect resources and “prioritize improvements” at the 5 sites currently using the new EHR: Spokane VA Health Care System, VA Walla Walla Health Care, Roseburg VA Health Care System, VA Southern Oregon Health Care, and VA Central Ohio Health Care System. Additional deployments will not be scheduled, the VA says, until it is confident that the new EHR is highly functioning at the current sites and ready to deliver at future sites, as demonstrated by “clear improvements” in the clinician and veteran experience, sustained high performance and high reliability.

“For the past few years, we’ve tried to fix this plane while flying it—and that hasn’t delivered the results that veterans or our staff deserve,” said Neil Evans, MD, acting program executive director at the Electronic Health Record Modernization Integration Office. “This reset changes that. We are going to take the time necessary to get this right for veterans and VA clinicians alike, and that means focusing our resources solely on improving the EHR at the sites where it is currently in use, and improving its fit for VA more broadly. In doing so, we will enhance the EHR for both current and future users, paving the way for successful future deployments.”  

The various EHR rollouts around the country have been bumpy from the beginning, operating by fits and starts as new problems surfaced and were addressed. To be fair, the whole implementation process only started in 2020 (and deployed at the first VA hospital during the COVID-19 pandemic), but in that time, the VA has had to, in its own words, “revise the timeline” again and again. The Boise VA Medical Center, for instance, was originally scheduled to go live June 25, 2022, then a month later—then 2023.

The VA Office of the Inspector General published 3 reports last year that found significant issues, including improperly routed clinical orders. VA Secretary Denis McDonough announced last July that the VA would delay EHR deployments until January 2023 to ensure that the system’s issues had been resolved. “During VA’s subsequent investigation at our current sites,” he said, “several additional technical and system issues were identified—including challenges with performance, such as latency and slowness, problems with patient scheduling, referrals, medication management, and other types of medical orders.”

In February, Ken Glueck, executive vice president of Oracle, wrote a blog post that was both apologia and explanation. Modernization, he said, “doesn’t come with a magic wand and there’s no easy button.”

After the DoD moved to Cerner for a new EHR system, the VA decided to follow suit. The goal was to create a “seamless, longitudinal record”—and that was the beginning of the largest health IT modernization project in history, Glueck said. And, although he didn’t mention it, the beginning of one of the VA’s biggest headaches. The problem, Glueck wrote, was that the new project involved “standardizing procedures and workflows that may have been different across 130 VistA implementations at largely autonomous VA medical centers.”

In June 2022—a significant month in the whole rollout process—Cerner was acquired by Oracle. By Glueck’s lights, that meant the VA “now has essentially 2 vendors for the price of one—one with extensive clinical expertise and one with extensive engineering expertise.”

Oracle, he said, “is hard at work to stabilize and improve performance; make fixes to functionality and design issues; improve training and build a better user experience.” He noted that significant improvements to the system’s capacity and performance have included reducing the most severe outage incidents by 67%.

In a recent statement, House VA Committee Chairman Mike Bost (R-IL) and Technology Modernization Subcommittee Chairman Matt Rosendale (R-MT) said, “We support Secretary McDonough’s decision in the strongest possible terms. The best way to get out of a hole is to stop digging, and we’re encouraged that VA and Oracle Cerner have finally realized that.”

VA and Oracle Cerner are currently working toward an amended contract that will "increase Oracle Cerner’s accountability to deliver a high-functioning, high-reliability, world-class EHR system,” the VA says. As part of the re-set, the VA also will work with Congress on resource requirements. The VA estimates FY 2023 costs will be reduced by $400 million. 

The painful paused and repaused rollout of the new Cerner electronic health record (EHR) system at the US Department of Veterans Affairs (VA) is now halted as the VA announces a “reset.” The decision applies to all planned deployments. An exception is the Captain James A. Lovell Federal Health Care Center in Chicago, the only fully integrated VA and US Department of Defense (DoD) health care system, which is expected go live in March 2024 as planned. The DoD rollout of its Cerner EHR is further along and expected to be completed in 2024.

The new plan is to redirect resources and “prioritize improvements” at the 5 sites currently using the new EHR: Spokane VA Health Care System, VA Walla Walla Health Care, Roseburg VA Health Care System, VA Southern Oregon Health Care, and VA Central Ohio Health Care System. Additional deployments will not be scheduled, the VA says, until it is confident that the new EHR is highly functioning at the current sites and ready to deliver at future sites, as demonstrated by “clear improvements” in the clinician and veteran experience, sustained high performance and high reliability.

“For the past few years, we’ve tried to fix this plane while flying it—and that hasn’t delivered the results that veterans or our staff deserve,” said Neil Evans, MD, acting program executive director at the Electronic Health Record Modernization Integration Office. “This reset changes that. We are going to take the time necessary to get this right for veterans and VA clinicians alike, and that means focusing our resources solely on improving the EHR at the sites where it is currently in use, and improving its fit for VA more broadly. In doing so, we will enhance the EHR for both current and future users, paving the way for successful future deployments.”  

The various EHR rollouts around the country have been bumpy from the beginning, operating by fits and starts as new problems surfaced and were addressed. To be fair, the whole implementation process only started in 2020 (and deployed at the first VA hospital during the COVID-19 pandemic), but in that time, the VA has had to, in its own words, “revise the timeline” again and again. The Boise VA Medical Center, for instance, was originally scheduled to go live June 25, 2022, then a month later—then 2023.

The VA Office of the Inspector General published 3 reports last year that found significant issues, including improperly routed clinical orders. VA Secretary Denis McDonough announced last July that the VA would delay EHR deployments until January 2023 to ensure that the system’s issues had been resolved. “During VA’s subsequent investigation at our current sites,” he said, “several additional technical and system issues were identified—including challenges with performance, such as latency and slowness, problems with patient scheduling, referrals, medication management, and other types of medical orders.”

In February, Ken Glueck, executive vice president of Oracle, wrote a blog post that was both apologia and explanation. Modernization, he said, “doesn’t come with a magic wand and there’s no easy button.”

After the DoD moved to Cerner for a new EHR system, the VA decided to follow suit. The goal was to create a “seamless, longitudinal record”—and that was the beginning of the largest health IT modernization project in history, Glueck said. And, although he didn’t mention it, the beginning of one of the VA’s biggest headaches. The problem, Glueck wrote, was that the new project involved “standardizing procedures and workflows that may have been different across 130 VistA implementations at largely autonomous VA medical centers.”

In June 2022—a significant month in the whole rollout process—Cerner was acquired by Oracle. By Glueck’s lights, that meant the VA “now has essentially 2 vendors for the price of one—one with extensive clinical expertise and one with extensive engineering expertise.”

Oracle, he said, “is hard at work to stabilize and improve performance; make fixes to functionality and design issues; improve training and build a better user experience.” He noted that significant improvements to the system’s capacity and performance have included reducing the most severe outage incidents by 67%.

In a recent statement, House VA Committee Chairman Mike Bost (R-IL) and Technology Modernization Subcommittee Chairman Matt Rosendale (R-MT) said, “We support Secretary McDonough’s decision in the strongest possible terms. The best way to get out of a hole is to stop digging, and we’re encouraged that VA and Oracle Cerner have finally realized that.”

VA and Oracle Cerner are currently working toward an amended contract that will "increase Oracle Cerner’s accountability to deliver a high-functioning, high-reliability, world-class EHR system,” the VA says. As part of the re-set, the VA also will work with Congress on resource requirements. The VA estimates FY 2023 costs will be reduced by $400 million. 

A genetic sequencing effort identified more patients to be carriers of risk genes for hereditary breast and ovarian cancer or Lynch syndrome than would have been discovered by following existing genetic testing guidelines, according to new research.

The authors of the clinical trial suggest that these guidelines may need to be revised.

Individuals with hereditary breast and ovarian cancer (HBOC) have an 80% lifetime risk of breast cancer and are at greater risk of ovarian cancer, pancreatic cancer, prostate cancer, and melanoma. Those with Lynch syndrome (LS) have an 80% lifetime risk of colorectal cancer, a 60% lifetime risk of endometrial cancer, and heightened risk of upper gastrointestinal, urinary tract, skin, and other tumors, said study coauthor N. Jewel Samadder, MD in a statement.

The National Cancer Control Network has guidelines for determining family risk for colorectal cancer and breast, ovarian, and pancreatic cancer to identify individuals who should be screened for LS and HBOC, but these rely on personal and family health histories.

“These criteria were created at a time when genetic testing was cost prohibitive and thus aimed to identify those at the greatest chance of being a mutation carrier in the absence of population-wide whole-exome sequencing. However, [LS and HBOC] are poorly identified in current practice, and many patients are not aware of their cancer risk,” said Dr. Samadder, professor of medicine and coleader of the precision oncology program at the Mayo Clinic Comprehensive Cancer Center, Phoenix, in the statement.

Whole-exome sequencing covers only protein-coding regions of the genome, which is less than 2% of the total genome but includes more than 85% of known disease-related genetic variants, according to Emily Gay, who presented the trial results (Abstract 5768) on April 18 at the annual meeting of the American Association for Cancer Research.

“In recent years, the cost of whole-exome sequencing has been rapidly decreasing, allowing us to complete this test on saliva samples from thousands, if not tens of thousands of patients covering large populations and large health systems,” said Ms. Gay, a genetic counseling graduate student at the University of Arizona, during her presentation.

She described results from the TAPESTRY clinical trial, with 44,306 participants from Mayo Clinic centers in Arizona, Florida, and Minnesota, who were identified as definitely or likely to be harboring pathogenic mutations and consented to whole-exome sequencing from saliva samples. They used electronic health records to determine whether patients would satisfy the testing criteria from NCCN guidelines.

The researchers identified 1.24% of participants to be carriers of HBOC or LS. Of the HBOC carriers, 62.8% were female, and of the LS carriers, 62.6% were female. The percentages of HBOC and LS carriers who were White were 88.6 and 94.5, respectively. The median age of both groups was 57 years. Of HBOC carriers, 47.3% had personal histories of cancers; for LS carries, the percentage was 44.2.

Of HBOC carriers, 49.1% had been previously unaware of their genetic condition, while an even higher percentage of patients with LS – 59.3% – fell into that category. Thirty-two percent of those with HBOC and 56.2% of those with LS would not have qualified for screening using the relevant NCCN guidelines.

“Most strikingly,” 63.8% of individuals with mutations in the MSH6 gene and 83.7% of those mutations in the PMS2 gene would not have met NCCN criteria, Ms. Gay said.

Having a cancer type not known to be related to a genetic syndrome was a reason for 58.6% of individuals failing to meet NCCN guidelines, while 60.5% did not meet the guidelines because of an insufficient number of relatives known to have a history of cancer, and 63.3% did not because they had no personal history of cancer. Among individuals with a pathogenic mutation who met NCCN criteria, 34% were not aware of their condition.

“This suggests that the NCCN guidelines are underutilized in clinical practice, potentially due to the busy schedule of clinicians or because the complexity of using these criteria,” said Ms. Gay.

The numbers were even more striking among minorities: “There is additional data analysis and research needed in this area, but based on our preliminary findings, we saw that nearly 50% of the individuals who are [part of an underrepresented minority group] did not meet criteria, compared with 32% of the white cohort,” said Ms. Gay.

Asked what new NCCN guidelines should be, Ms. Gay replied: “I think maybe limiting the number of relatives that you have to have with a certain type of cancer, especially as we see families get smaller and smaller, especially in the United States – that family data isn’t necessarily available or as useful. And then also, I think, incorporating in the size of a family into the calculation, so more of maybe a point-based system like we see with other genetic conditions rather than a ‘yes you meet or no, you don’t.’ More of a range to say ‘you fall on the low-risk, medium-risk, or high-risk stage,’” said Ms. Gay.

During the Q&A period, session cochair Andrew Godwin, PhD, who is a professor of molecular oncology and pathology at University of Kansas Medical Center, Kansas City, said he wondered if whole-exome sequencing was capable of picking up cancer risk mutations that standard targeted tests don’t look for.

Dr. Samadder, who was in the audience, answered the question, saying that targeted tests are actually better at picking up some types of mutations like intronic mutations, single-nucleotide polymorphisms, and deletions.

“There are some limitations to whole-exome sequencing. Our estimate here of 1.2% [of participants carrying HBOC or LS mutations] is probably an underestimate. There are additional variants that exome sequencing probably doesn’t pick up easily or as well. That’s why we qualify that exome sequencing is a screening test, not a diagnostic,” he continued.

Ms. Gay and Dr. Samadder have no relevant financial disclosures. Dr. Godwin has financial relationships with Clara Biotech, VITRAC Therapeutics, and Sinochips Diagnostics.

A genetic sequencing effort identified more patients to be carriers of risk genes for hereditary breast and ovarian cancer or Lynch syndrome than would have been discovered by following existing genetic testing guidelines, according to new research.

The authors of the clinical trial suggest that these guidelines may need to be revised.

Individuals with hereditary breast and ovarian cancer (HBOC) have an 80% lifetime risk of breast cancer and are at greater risk of ovarian cancer, pancreatic cancer, prostate cancer, and melanoma. Those with Lynch syndrome (LS) have an 80% lifetime risk of colorectal cancer, a 60% lifetime risk of endometrial cancer, and heightened risk of upper gastrointestinal, urinary tract, skin, and other tumors, said study coauthor N. Jewel Samadder, MD in a statement.

The National Cancer Control Network has guidelines for determining family risk for colorectal cancer and breast, ovarian, and pancreatic cancer to identify individuals who should be screened for LS and HBOC, but these rely on personal and family health histories.

“These criteria were created at a time when genetic testing was cost prohibitive and thus aimed to identify those at the greatest chance of being a mutation carrier in the absence of population-wide whole-exome sequencing. However, [LS and HBOC] are poorly identified in current practice, and many patients are not aware of their cancer risk,” said Dr. Samadder, professor of medicine and coleader of the precision oncology program at the Mayo Clinic Comprehensive Cancer Center, Phoenix, in the statement.

Whole-exome sequencing covers only protein-coding regions of the genome, which is less than 2% of the total genome but includes more than 85% of known disease-related genetic variants, according to Emily Gay, who presented the trial results (Abstract 5768) on April 18 at the annual meeting of the American Association for Cancer Research.

“In recent years, the cost of whole-exome sequencing has been rapidly decreasing, allowing us to complete this test on saliva samples from thousands, if not tens of thousands of patients covering large populations and large health systems,” said Ms. Gay, a genetic counseling graduate student at the University of Arizona, during her presentation.

She described results from the TAPESTRY clinical trial, with 44,306 participants from Mayo Clinic centers in Arizona, Florida, and Minnesota, who were identified as definitely or likely to be harboring pathogenic mutations and consented to whole-exome sequencing from saliva samples. They used electronic health records to determine whether patients would satisfy the testing criteria from NCCN guidelines.

The researchers identified 1.24% of participants to be carriers of HBOC or LS. Of the HBOC carriers, 62.8% were female, and of the LS carriers, 62.6% were female. The percentages of HBOC and LS carriers who were White were 88.6 and 94.5, respectively. The median age of both groups was 57 years. Of HBOC carriers, 47.3% had personal histories of cancers; for LS carries, the percentage was 44.2.

Of HBOC carriers, 49.1% had been previously unaware of their genetic condition, while an even higher percentage of patients with LS – 59.3% – fell into that category. Thirty-two percent of those with HBOC and 56.2% of those with LS would not have qualified for screening using the relevant NCCN guidelines.

“Most strikingly,” 63.8% of individuals with mutations in the MSH6 gene and 83.7% of those mutations in the PMS2 gene would not have met NCCN criteria, Ms. Gay said.

Having a cancer type not known to be related to a genetic syndrome was a reason for 58.6% of individuals failing to meet NCCN guidelines, while 60.5% did not meet the guidelines because of an insufficient number of relatives known to have a history of cancer, and 63.3% did not because they had no personal history of cancer. Among individuals with a pathogenic mutation who met NCCN criteria, 34% were not aware of their condition.

“This suggests that the NCCN guidelines are underutilized in clinical practice, potentially due to the busy schedule of clinicians or because the complexity of using these criteria,” said Ms. Gay.

The numbers were even more striking among minorities: “There is additional data analysis and research needed in this area, but based on our preliminary findings, we saw that nearly 50% of the individuals who are [part of an underrepresented minority group] did not meet criteria, compared with 32% of the white cohort,” said Ms. Gay.

Asked what new NCCN guidelines should be, Ms. Gay replied: “I think maybe limiting the number of relatives that you have to have with a certain type of cancer, especially as we see families get smaller and smaller, especially in the United States – that family data isn’t necessarily available or as useful. And then also, I think, incorporating in the size of a family into the calculation, so more of maybe a point-based system like we see with other genetic conditions rather than a ‘yes you meet or no, you don’t.’ More of a range to say ‘you fall on the low-risk, medium-risk, or high-risk stage,’” said Ms. Gay.

During the Q&A period, session cochair Andrew Godwin, PhD, who is a professor of molecular oncology and pathology at University of Kansas Medical Center, Kansas City, said he wondered if whole-exome sequencing was capable of picking up cancer risk mutations that standard targeted tests don’t look for.

Dr. Samadder, who was in the audience, answered the question, saying that targeted tests are actually better at picking up some types of mutations like intronic mutations, single-nucleotide polymorphisms, and deletions.

“There are some limitations to whole-exome sequencing. Our estimate here of 1.2% [of participants carrying HBOC or LS mutations] is probably an underestimate. There are additional variants that exome sequencing probably doesn’t pick up easily or as well. That’s why we qualify that exome sequencing is a screening test, not a diagnostic,” he continued.

Ms. Gay and Dr. Samadder have no relevant financial disclosures. Dr. Godwin has financial relationships with Clara Biotech, VITRAC Therapeutics, and Sinochips Diagnostics.

A genetic sequencing effort identified more patients to be carriers of risk genes for hereditary breast and ovarian cancer or Lynch syndrome than would have been discovered by following existing genetic testing guidelines, according to new research.

The authors of the clinical trial suggest that these guidelines may need to be revised.

Individuals with hereditary breast and ovarian cancer (HBOC) have an 80% lifetime risk of breast cancer and are at greater risk of ovarian cancer, pancreatic cancer, prostate cancer, and melanoma. Those with Lynch syndrome (LS) have an 80% lifetime risk of colorectal cancer, a 60% lifetime risk of endometrial cancer, and heightened risk of upper gastrointestinal, urinary tract, skin, and other tumors, said study coauthor N. Jewel Samadder, MD in a statement.

The National Cancer Control Network has guidelines for determining family risk for colorectal cancer and breast, ovarian, and pancreatic cancer to identify individuals who should be screened for LS and HBOC, but these rely on personal and family health histories.

“These criteria were created at a time when genetic testing was cost prohibitive and thus aimed to identify those at the greatest chance of being a mutation carrier in the absence of population-wide whole-exome sequencing. However, [LS and HBOC] are poorly identified in current practice, and many patients are not aware of their cancer risk,” said Dr. Samadder, professor of medicine and coleader of the precision oncology program at the Mayo Clinic Comprehensive Cancer Center, Phoenix, in the statement.

Whole-exome sequencing covers only protein-coding regions of the genome, which is less than 2% of the total genome but includes more than 85% of known disease-related genetic variants, according to Emily Gay, who presented the trial results (Abstract 5768) on April 18 at the annual meeting of the American Association for Cancer Research.

“In recent years, the cost of whole-exome sequencing has been rapidly decreasing, allowing us to complete this test on saliva samples from thousands, if not tens of thousands of patients covering large populations and large health systems,” said Ms. Gay, a genetic counseling graduate student at the University of Arizona, during her presentation.

She described results from the TAPESTRY clinical trial, with 44,306 participants from Mayo Clinic centers in Arizona, Florida, and Minnesota, who were identified as definitely or likely to be harboring pathogenic mutations and consented to whole-exome sequencing from saliva samples. They used electronic health records to determine whether patients would satisfy the testing criteria from NCCN guidelines.

The researchers identified 1.24% of participants to be carriers of HBOC or LS. Of the HBOC carriers, 62.8% were female, and of the LS carriers, 62.6% were female. The percentages of HBOC and LS carriers who were White were 88.6 and 94.5, respectively. The median age of both groups was 57 years. Of HBOC carriers, 47.3% had personal histories of cancers; for LS carries, the percentage was 44.2.

Of HBOC carriers, 49.1% had been previously unaware of their genetic condition, while an even higher percentage of patients with LS – 59.3% – fell into that category. Thirty-two percent of those with HBOC and 56.2% of those with LS would not have qualified for screening using the relevant NCCN guidelines.

“Most strikingly,” 63.8% of individuals with mutations in the MSH6 gene and 83.7% of those mutations in the PMS2 gene would not have met NCCN criteria, Ms. Gay said.

Having a cancer type not known to be related to a genetic syndrome was a reason for 58.6% of individuals failing to meet NCCN guidelines, while 60.5% did not meet the guidelines because of an insufficient number of relatives known to have a history of cancer, and 63.3% did not because they had no personal history of cancer. Among individuals with a pathogenic mutation who met NCCN criteria, 34% were not aware of their condition.

“This suggests that the NCCN guidelines are underutilized in clinical practice, potentially due to the busy schedule of clinicians or because the complexity of using these criteria,” said Ms. Gay.

The numbers were even more striking among minorities: “There is additional data analysis and research needed in this area, but based on our preliminary findings, we saw that nearly 50% of the individuals who are [part of an underrepresented minority group] did not meet criteria, compared with 32% of the white cohort,” said Ms. Gay.

Asked what new NCCN guidelines should be, Ms. Gay replied: “I think maybe limiting the number of relatives that you have to have with a certain type of cancer, especially as we see families get smaller and smaller, especially in the United States – that family data isn’t necessarily available or as useful. And then also, I think, incorporating in the size of a family into the calculation, so more of maybe a point-based system like we see with other genetic conditions rather than a ‘yes you meet or no, you don’t.’ More of a range to say ‘you fall on the low-risk, medium-risk, or high-risk stage,’” said Ms. Gay.

During the Q&A period, session cochair Andrew Godwin, PhD, who is a professor of molecular oncology and pathology at University of Kansas Medical Center, Kansas City, said he wondered if whole-exome sequencing was capable of picking up cancer risk mutations that standard targeted tests don’t look for.

Dr. Samadder, who was in the audience, answered the question, saying that targeted tests are actually better at picking up some types of mutations like intronic mutations, single-nucleotide polymorphisms, and deletions.

“There are some limitations to whole-exome sequencing. Our estimate here of 1.2% [of participants carrying HBOC or LS mutations] is probably an underestimate. There are additional variants that exome sequencing probably doesn’t pick up easily or as well. That’s why we qualify that exome sequencing is a screening test, not a diagnostic,” he continued.

Ms. Gay and Dr. Samadder have no relevant financial disclosures. Dr. Godwin has financial relationships with Clara Biotech, VITRAC Therapeutics, and Sinochips Diagnostics.

The Janus kinase (JAK) inhibitor upadacitinib is an effective and well-tolerated treatment option for adolescents with moderate to severe atopic dermatitis (AD), an analysis of three clinical trials reports.

Upadacitinib (Rinvoq) was approved by the Food and Drug Administration for treating adults and pediatric patients 12 years of age and older with refractory, moderate to severe AD, in January 2022. This study analyzed the adolescent data in three double-blind, placebo-controlled phase 3 randomized clinical trials, which included adults and 552 adolescents between 12 and 17 years of age with moderate to severe AD in more than 20 countries in Europe, North and South America, the Middle East, Oceania, and the Asia-Pacific region from July 2018 through December 2020.

In the studies, “treatment of moderate to severe AD in adolescents with upadacitinib was effective and generally well tolerated, with an overall efficacy and safety profile similar to that observed in adults, and patient-reported outcomes indicated an overall better health-related quality of life compared with placebo,” lead study author Amy S. Paller, MD, chair of the department of dermatology and professor of dermatology and pediatrics, at Northwestern University, Chicago, and her colleagues write in JAMA Dermatology.

Adolescents in the three studies – Measure Up 1, Measure Up 2, and AD Up – received once-daily oral upadacitinib 15 mg, 30 mg, or placebo. All participants in AD Up used topical corticosteroids.

At 16 weeks, in Measure Up 1, Measure Up 2, and AD Up, respectively, a greater proportion of adolescents improved by at least 75% in the Eczema Area and Severity Index (EASI 75) with upadacitinib 15 mg (73%, 69%, 63%); and with upadacitinib 30 mg (78%, 73%, 84%), compared with placebo (12%, 13%, 30%), (P < .001 for all comparisons vs. placebo).

Upadacitinib was generally well tolerated among the adolescents, with mild or moderate acne being the most common adverse event, reported in 10%-13% of those on 15 mg and 15%-16% of those on 30 mg vs. 2%-3% of those on placebo.

Asked to comment on the study, Peck Ong, MD, a pediatric allergist and immunologist at Children’s Hospital Los Angeles, said that he was not surprised by the drug’s effectiveness because JAK inhibitors are potent immunosuppressants. Strengths of the studies include the many pediatric participants, its international reach, and its use of standardized and validated measures, said Dr. Ong, who was not involved in the study.

“The effect of JAK inhibitors is more specific than traditional immunosuppressants such as cyclosporine and methotrexate but not as specific as biologics; therefore, long-term safety data are needed,” he advised. “16 weeks is a very short time to study a chronic disease like atopic dermatitis. We need safety data longer than 1 year.”

Given the disease’s potential impact on self-esteem, sleep, and other important areas of life, Sean Reynolds, MBBCH, a pediatric dermatologist at Children’s Mercy Kansas City (Mo.), welcomed the data on the newer pharmacologic agents.

“FDA-approved systemic treatment options for adolescents with AD are currently limited, which necessitates studies such as this that explore additional treatment options,” said Dr. Reynolds, who also was not involved in the study, told this news organization.

He added that oral upadacitinib may especially help patients who have not found relief with other topical or systemic treatments or who are needle phobic. While the overall efficacy and relatively mild side effects for most patients taking upadacitinib in the trials are encouraging, “the long-term efficacy and side effects in this population require further study, especially considering the limited systemic AD treatment options available in this age group,” he added.

“Given the reported use of other JAK inhibitors to treat myriad inflammatory skin conditions beyond atopic dermatitis, the potential use of upadacitinib and other JAK inhibitors to treat these skin diseases in children and adolescents represents an exciting area for future study in the field of pediatric dermatology,” Dr. Reynolds noted.

The study was funded by AbbVie, the developer and manufacturer of upadacitinib. Dr. Paller and almost all other authors reported relevant financial relationships with AbbVie and other pharmaceutical companies. Dr. Ong reported serving on an AbbVie advisory board, and Dr. Reynolds reported no conflict of interest with the study.

The Janus kinase (JAK) inhibitor upadacitinib is an effective and well-tolerated treatment option for adolescents with moderate to severe atopic dermatitis (AD), an analysis of three clinical trials reports.

Upadacitinib (Rinvoq) was approved by the Food and Drug Administration for treating adults and pediatric patients 12 years of age and older with refractory, moderate to severe AD, in January 2022. This study analyzed the adolescent data in three double-blind, placebo-controlled phase 3 randomized clinical trials, which included adults and 552 adolescents between 12 and 17 years of age with moderate to severe AD in more than 20 countries in Europe, North and South America, the Middle East, Oceania, and the Asia-Pacific region from July 2018 through December 2020.

In the studies, “treatment of moderate to severe AD in adolescents with upadacitinib was effective and generally well tolerated, with an overall efficacy and safety profile similar to that observed in adults, and patient-reported outcomes indicated an overall better health-related quality of life compared with placebo,” lead study author Amy S. Paller, MD, chair of the department of dermatology and professor of dermatology and pediatrics, at Northwestern University, Chicago, and her colleagues write in JAMA Dermatology.

Adolescents in the three studies – Measure Up 1, Measure Up 2, and AD Up – received once-daily oral upadacitinib 15 mg, 30 mg, or placebo. All participants in AD Up used topical corticosteroids.

At 16 weeks, in Measure Up 1, Measure Up 2, and AD Up, respectively, a greater proportion of adolescents improved by at least 75% in the Eczema Area and Severity Index (EASI 75) with upadacitinib 15 mg (73%, 69%, 63%); and with upadacitinib 30 mg (78%, 73%, 84%), compared with placebo (12%, 13%, 30%), (P < .001 for all comparisons vs. placebo).

Upadacitinib was generally well tolerated among the adolescents, with mild or moderate acne being the most common adverse event, reported in 10%-13% of those on 15 mg and 15%-16% of those on 30 mg vs. 2%-3% of those on placebo.

Asked to comment on the study, Peck Ong, MD, a pediatric allergist and immunologist at Children’s Hospital Los Angeles, said that he was not surprised by the drug’s effectiveness because JAK inhibitors are potent immunosuppressants. Strengths of the studies include the many pediatric participants, its international reach, and its use of standardized and validated measures, said Dr. Ong, who was not involved in the study.

“The effect of JAK inhibitors is more specific than traditional immunosuppressants such as cyclosporine and methotrexate but not as specific as biologics; therefore, long-term safety data are needed,” he advised. “16 weeks is a very short time to study a chronic disease like atopic dermatitis. We need safety data longer than 1 year.”

Given the disease’s potential impact on self-esteem, sleep, and other important areas of life, Sean Reynolds, MBBCH, a pediatric dermatologist at Children’s Mercy Kansas City (Mo.), welcomed the data on the newer pharmacologic agents.

“FDA-approved systemic treatment options for adolescents with AD are currently limited, which necessitates studies such as this that explore additional treatment options,” said Dr. Reynolds, who also was not involved in the study, told this news organization.

He added that oral upadacitinib may especially help patients who have not found relief with other topical or systemic treatments or who are needle phobic. While the overall efficacy and relatively mild side effects for most patients taking upadacitinib in the trials are encouraging, “the long-term efficacy and side effects in this population require further study, especially considering the limited systemic AD treatment options available in this age group,” he added.

“Given the reported use of other JAK inhibitors to treat myriad inflammatory skin conditions beyond atopic dermatitis, the potential use of upadacitinib and other JAK inhibitors to treat these skin diseases in children and adolescents represents an exciting area for future study in the field of pediatric dermatology,” Dr. Reynolds noted.

The study was funded by AbbVie, the developer and manufacturer of upadacitinib. Dr. Paller and almost all other authors reported relevant financial relationships with AbbVie and other pharmaceutical companies. Dr. Ong reported serving on an AbbVie advisory board, and Dr. Reynolds reported no conflict of interest with the study.

The Janus kinase (JAK) inhibitor upadacitinib is an effective and well-tolerated treatment option for adolescents with moderate to severe atopic dermatitis (AD), an analysis of three clinical trials reports.

Upadacitinib (Rinvoq) was approved by the Food and Drug Administration for treating adults and pediatric patients 12 years of age and older with refractory, moderate to severe AD, in January 2022. This study analyzed the adolescent data in three double-blind, placebo-controlled phase 3 randomized clinical trials, which included adults and 552 adolescents between 12 and 17 years of age with moderate to severe AD in more than 20 countries in Europe, North and South America, the Middle East, Oceania, and the Asia-Pacific region from July 2018 through December 2020.

In the studies, “treatment of moderate to severe AD in adolescents with upadacitinib was effective and generally well tolerated, with an overall efficacy and safety profile similar to that observed in adults, and patient-reported outcomes indicated an overall better health-related quality of life compared with placebo,” lead study author Amy S. Paller, MD, chair of the department of dermatology and professor of dermatology and pediatrics, at Northwestern University, Chicago, and her colleagues write in JAMA Dermatology.

Adolescents in the three studies – Measure Up 1, Measure Up 2, and AD Up – received once-daily oral upadacitinib 15 mg, 30 mg, or placebo. All participants in AD Up used topical corticosteroids.

At 16 weeks, in Measure Up 1, Measure Up 2, and AD Up, respectively, a greater proportion of adolescents improved by at least 75% in the Eczema Area and Severity Index (EASI 75) with upadacitinib 15 mg (73%, 69%, 63%); and with upadacitinib 30 mg (78%, 73%, 84%), compared with placebo (12%, 13%, 30%), (P < .001 for all comparisons vs. placebo).

Upadacitinib was generally well tolerated among the adolescents, with mild or moderate acne being the most common adverse event, reported in 10%-13% of those on 15 mg and 15%-16% of those on 30 mg vs. 2%-3% of those on placebo.

Asked to comment on the study, Peck Ong, MD, a pediatric allergist and immunologist at Children’s Hospital Los Angeles, said that he was not surprised by the drug’s effectiveness because JAK inhibitors are potent immunosuppressants. Strengths of the studies include the many pediatric participants, its international reach, and its use of standardized and validated measures, said Dr. Ong, who was not involved in the study.

“The effect of JAK inhibitors is more specific than traditional immunosuppressants such as cyclosporine and methotrexate but not as specific as biologics; therefore, long-term safety data are needed,” he advised. “16 weeks is a very short time to study a chronic disease like atopic dermatitis. We need safety data longer than 1 year.”

Given the disease’s potential impact on self-esteem, sleep, and other important areas of life, Sean Reynolds, MBBCH, a pediatric dermatologist at Children’s Mercy Kansas City (Mo.), welcomed the data on the newer pharmacologic agents.

“FDA-approved systemic treatment options for adolescents with AD are currently limited, which necessitates studies such as this that explore additional treatment options,” said Dr. Reynolds, who also was not involved in the study, told this news organization.

He added that oral upadacitinib may especially help patients who have not found relief with other topical or systemic treatments or who are needle phobic. While the overall efficacy and relatively mild side effects for most patients taking upadacitinib in the trials are encouraging, “the long-term efficacy and side effects in this population require further study, especially considering the limited systemic AD treatment options available in this age group,” he added.

“Given the reported use of other JAK inhibitors to treat myriad inflammatory skin conditions beyond atopic dermatitis, the potential use of upadacitinib and other JAK inhibitors to treat these skin diseases in children and adolescents represents an exciting area for future study in the field of pediatric dermatology,” Dr. Reynolds noted.

The study was funded by AbbVie, the developer and manufacturer of upadacitinib. Dr. Paller and almost all other authors reported relevant financial relationships with AbbVie and other pharmaceutical companies. Dr. Ong reported serving on an AbbVie advisory board, and Dr. Reynolds reported no conflict of interest with the study.

BOSTON – An experimental neural cell therapy is safe and led to greater than 90% reduction in seizures in two patients with drug-resistant mesial temporal lobe epilepsy (MTLE) in the first-in-human test of the novel therapy.

“It is notable that the early significant seizure reduction observed in this study appears to be durable in these first two patients treated with a single administration of NRTX-1001,” principal investigator Robert Beach, MD, PhD, said in a news release.

“It is also encouraging that the first patient has been free from disabling seizures from the second month on and has shown improved memory performance on multiple cognitive tests, as memory problems can be an issue for individuals with drug-resistant MTLE,” said Dr. Beach, chief of epilepsy and professor of neurology at State University of New York, Syracuse.

The findings were presented at the annual meeting of the American Academy of Neurology.
 

Restorative not destructive

NRTX-1001 therapy (Neurona Therapeutics) is a one-time dose of an injectable suspension of high-purity inhibitory interneurons that secrete the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). The interneurons are intended to integrate and innervate on-target, providing long-term GABAergic inhibition to repair hyperexcitable neural networks.

Preclinical work in animal models of epilepsy has provided strong support for both the safety and the efficacy of boosting inhibition in the seizure focus using implanted human inhibitory interneurons.

This therapy is “potentially restorative instead of just destructive, like epilepsy surgery,” study investigator David Spencer, MD, professor of neurology and director of the Comprehensive Epilepsy Center, Oregon Health & Science University in Portland, said during a press briefing.

In the first two patients, the cells were implanted in the seizure focus using MRI guidance through a tiny opening in the back of the skull. The patients recovered overnight and went home the next day.

The first patient had a 9-year history of drug-resistant epilepsy and was averaging 30 seizures per month at baseline. Testing confirmed that the seizures were coming from a single focus on the right temporal lobe. The implant was uncomplicated, and the cells were delivered to the seizure focus on target.

To date, there have been no serious or unexpected adverse events from the implant. At 9 months of follow-up the patient has had a 93% reduction in seizures overall and is free of all seizures causing impairment of awareness, “which was the most debilitating seizure type for this patient,” Dr. Spencer noted.

Studies of brain metabolism in the area of the implant have shown favorable markers of increased inhibition and decreased inflammation. Cognitive testing at 6 months showed no worsening of memory function or cognition. And, in fact, there were some mild improvements, he said.

The second patient had an 8-year history of drug-resistant epilepsy, averaging 14 focal seizures per month at baseline. Testing also confirmed seizure onset in a single focus in the right temporal lobe and the cells were again implanted without complication on target. Five months after treatment, the patient has had a 94% reduction in seizures and no serious adverse events.
 

‘Hot off the press’

Epilepsy affects about 3.5 million people in the United States. About two-thirds of people with epilepsy get good control of their seizures using antiseizure medication.

For seizures that are uncontrolled with medication, identifying the seizure focus and removing it surgically can often result in seizure freedom in a high proportion of patients. But not all patients are candidates for epilepsy surgery, and for those who can have it the surgery itself carries some risks, including diminished cognition and memory.

“While these are still early days, we’re encouraged by the positive safety findings so far, and the early seizure responses” with neural cell therapy, Dr. Spencer told reporters.

Given the positive results in the first two patients, additional patients will be treated “with careful safety review all along the way. This is going to be rolling out over the next several years,” Dr. Spencer said. Patient recruitment is underway at epilepsy centers across the United States.

Briefing moderator Natalia Rost, MD, MPH, chair of the AAN science committee, said, “This is a true example of emerging science. It’s literally hot off the press,” and the preliminary results are “very promising.”

Dr. Rost, chief of the stroke division at Massachusetts General Hospital in Boston, noted that this type of cell therapy implant is “very novel and representative of where the field is moving, when no traditional solutions exist for common neurological problems.” 

The study was sponsored by Neurona Therapeutics and funded in part by the California Institute for Regenerative Medicine. Dr. Beach and Dr. Spencer report no relevant financial relationships. Several investigators are employees of Neurona Therapeutics. Dr. Rost reports no relevant financial relationships.

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

BOSTON – An experimental neural cell therapy is safe and led to greater than 90% reduction in seizures in two patients with drug-resistant mesial temporal lobe epilepsy (MTLE) in the first-in-human test of the novel therapy.

“It is notable that the early significant seizure reduction observed in this study appears to be durable in these first two patients treated with a single administration of NRTX-1001,” principal investigator Robert Beach, MD, PhD, said in a news release.

“It is also encouraging that the first patient has been free from disabling seizures from the second month on and has shown improved memory performance on multiple cognitive tests, as memory problems can be an issue for individuals with drug-resistant MTLE,” said Dr. Beach, chief of epilepsy and professor of neurology at State University of New York, Syracuse.

The findings were presented at the annual meeting of the American Academy of Neurology.
 

Restorative not destructive

NRTX-1001 therapy (Neurona Therapeutics) is a one-time dose of an injectable suspension of high-purity inhibitory interneurons that secrete the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). The interneurons are intended to integrate and innervate on-target, providing long-term GABAergic inhibition to repair hyperexcitable neural networks.

Preclinical work in animal models of epilepsy has provided strong support for both the safety and the efficacy of boosting inhibition in the seizure focus using implanted human inhibitory interneurons.

This therapy is “potentially restorative instead of just destructive, like epilepsy surgery,” study investigator David Spencer, MD, professor of neurology and director of the Comprehensive Epilepsy Center, Oregon Health & Science University in Portland, said during a press briefing.

In the first two patients, the cells were implanted in the seizure focus using MRI guidance through a tiny opening in the back of the skull. The patients recovered overnight and went home the next day.

The first patient had a 9-year history of drug-resistant epilepsy and was averaging 30 seizures per month at baseline. Testing confirmed that the seizures were coming from a single focus on the right temporal lobe. The implant was uncomplicated, and the cells were delivered to the seizure focus on target.

To date, there have been no serious or unexpected adverse events from the implant. At 9 months of follow-up the patient has had a 93% reduction in seizures overall and is free of all seizures causing impairment of awareness, “which was the most debilitating seizure type for this patient,” Dr. Spencer noted.

Studies of brain metabolism in the area of the implant have shown favorable markers of increased inhibition and decreased inflammation. Cognitive testing at 6 months showed no worsening of memory function or cognition. And, in fact, there were some mild improvements, he said.

The second patient had an 8-year history of drug-resistant epilepsy, averaging 14 focal seizures per month at baseline. Testing also confirmed seizure onset in a single focus in the right temporal lobe and the cells were again implanted without complication on target. Five months after treatment, the patient has had a 94% reduction in seizures and no serious adverse events.
 

‘Hot off the press’

Epilepsy affects about 3.5 million people in the United States. About two-thirds of people with epilepsy get good control of their seizures using antiseizure medication.

For seizures that are uncontrolled with medication, identifying the seizure focus and removing it surgically can often result in seizure freedom in a high proportion of patients. But not all patients are candidates for epilepsy surgery, and for those who can have it the surgery itself carries some risks, including diminished cognition and memory.

“While these are still early days, we’re encouraged by the positive safety findings so far, and the early seizure responses” with neural cell therapy, Dr. Spencer told reporters.

Given the positive results in the first two patients, additional patients will be treated “with careful safety review all along the way. This is going to be rolling out over the next several years,” Dr. Spencer said. Patient recruitment is underway at epilepsy centers across the United States.

Briefing moderator Natalia Rost, MD, MPH, chair of the AAN science committee, said, “This is a true example of emerging science. It’s literally hot off the press,” and the preliminary results are “very promising.”

Dr. Rost, chief of the stroke division at Massachusetts General Hospital in Boston, noted that this type of cell therapy implant is “very novel and representative of where the field is moving, when no traditional solutions exist for common neurological problems.” 

The study was sponsored by Neurona Therapeutics and funded in part by the California Institute for Regenerative Medicine. Dr. Beach and Dr. Spencer report no relevant financial relationships. Several investigators are employees of Neurona Therapeutics. Dr. Rost reports no relevant financial relationships.

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

BOSTON – An experimental neural cell therapy is safe and led to greater than 90% reduction in seizures in two patients with drug-resistant mesial temporal lobe epilepsy (MTLE) in the first-in-human test of the novel therapy.

“It is notable that the early significant seizure reduction observed in this study appears to be durable in these first two patients treated with a single administration of NRTX-1001,” principal investigator Robert Beach, MD, PhD, said in a news release.

“It is also encouraging that the first patient has been free from disabling seizures from the second month on and has shown improved memory performance on multiple cognitive tests, as memory problems can be an issue for individuals with drug-resistant MTLE,” said Dr. Beach, chief of epilepsy and professor of neurology at State University of New York, Syracuse.

The findings were presented at the annual meeting of the American Academy of Neurology.
 

Restorative not destructive

NRTX-1001 therapy (Neurona Therapeutics) is a one-time dose of an injectable suspension of high-purity inhibitory interneurons that secrete the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). The interneurons are intended to integrate and innervate on-target, providing long-term GABAergic inhibition to repair hyperexcitable neural networks.

Preclinical work in animal models of epilepsy has provided strong support for both the safety and the efficacy of boosting inhibition in the seizure focus using implanted human inhibitory interneurons.

This therapy is “potentially restorative instead of just destructive, like epilepsy surgery,” study investigator David Spencer, MD, professor of neurology and director of the Comprehensive Epilepsy Center, Oregon Health & Science University in Portland, said during a press briefing.

In the first two patients, the cells were implanted in the seizure focus using MRI guidance through a tiny opening in the back of the skull. The patients recovered overnight and went home the next day.

The first patient had a 9-year history of drug-resistant epilepsy and was averaging 30 seizures per month at baseline. Testing confirmed that the seizures were coming from a single focus on the right temporal lobe. The implant was uncomplicated, and the cells were delivered to the seizure focus on target.

To date, there have been no serious or unexpected adverse events from the implant. At 9 months of follow-up the patient has had a 93% reduction in seizures overall and is free of all seizures causing impairment of awareness, “which was the most debilitating seizure type for this patient,” Dr. Spencer noted.

Studies of brain metabolism in the area of the implant have shown favorable markers of increased inhibition and decreased inflammation. Cognitive testing at 6 months showed no worsening of memory function or cognition. And, in fact, there were some mild improvements, he said.

The second patient had an 8-year history of drug-resistant epilepsy, averaging 14 focal seizures per month at baseline. Testing also confirmed seizure onset in a single focus in the right temporal lobe and the cells were again implanted without complication on target. Five months after treatment, the patient has had a 94% reduction in seizures and no serious adverse events.
 

‘Hot off the press’

Epilepsy affects about 3.5 million people in the United States. About two-thirds of people with epilepsy get good control of their seizures using antiseizure medication.

For seizures that are uncontrolled with medication, identifying the seizure focus and removing it surgically can often result in seizure freedom in a high proportion of patients. But not all patients are candidates for epilepsy surgery, and for those who can have it the surgery itself carries some risks, including diminished cognition and memory.

“While these are still early days, we’re encouraged by the positive safety findings so far, and the early seizure responses” with neural cell therapy, Dr. Spencer told reporters.

Given the positive results in the first two patients, additional patients will be treated “with careful safety review all along the way. This is going to be rolling out over the next several years,” Dr. Spencer said. Patient recruitment is underway at epilepsy centers across the United States.

Briefing moderator Natalia Rost, MD, MPH, chair of the AAN science committee, said, “This is a true example of emerging science. It’s literally hot off the press,” and the preliminary results are “very promising.”

Dr. Rost, chief of the stroke division at Massachusetts General Hospital in Boston, noted that this type of cell therapy implant is “very novel and representative of where the field is moving, when no traditional solutions exist for common neurological problems.” 

The study was sponsored by Neurona Therapeutics and funded in part by the California Institute for Regenerative Medicine. Dr. Beach and Dr. Spencer report no relevant financial relationships. Several investigators are employees of Neurona Therapeutics. Dr. Rost reports no relevant financial relationships.

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

BOSTON – The neurologic symptoms of long COVID appear to be explained by a phenomenon known as antigenic imprinting, which involves a misdirected immune response to the SARS-CoV2 virus, according to a collaborative study presented at the 2023 annual meeting of the American Academy of Neurology.

Already documented in several other viral infections, such as influenza and human immunodeficiency virus, antigenic imprinting results in production of antibodies to previously encountered viral infections rather than to the immediate threat, according to Marianna Spatola, MD, PhD, a research fellow at the Ragon Institute, Harvard University, Cambridge, Mass.
 

Original antigenic sin

In the case of persistent neurologic symptoms after COVID, a condition known as neuroPASC (neurological postacute sequelae of SARS-CoV2 infection), antibodies produced for previously encountered coronaviruses rather than for SARS-CoV2 might explain most or all cases, according to the data Dr. Spatola presented.

The evidence for this explanation was drawn from a study of 112 patients evaluated months after an acute episode of COVID-19. Of these, 18 patients had persistent neurologic dysfunction. When compared with the 94 whose infection resolved without sequelae, the patients with prolonged neurologic impairments had relatively low systemic antibody response to SARS-CoV2. However, they showed relatively high antibody responses against other coronaviruses.

This is a pattern consistent with antigenic imprinting, a concept first described more than 60 years ago as original antigenic sin. When the immune system becomes imprinted with an antigen from the first encountered virus from a family of pathogens, it governs all subsequent antibody responses, according to several published studies that have described and evaluated this concept.
 

Additional evidence

In Dr. Spatola’s study, other differences, particularly in regard to the cerebrospinal fluid (CSF), further supported the role of antigenic imprinting as a cause of neuroPASC. For one, those with elevated immune responses to other common coronaviruses rather than SARS-CoV2 in the CSF relative to the periphery were more likely to have a bad outcome in regard to neurologic symptoms.

Moreover, the CSF in neuroPASC patients “was characterized by increased IgG1 and absence of IgM, suggesting compartmentalized humoral responses within the CSF through selective transfer of antibodies from the serum to the CSF across the blood-brain barrier rather than through intrathecal synthesis,” Dr. Spatola reported.

In the case of COVID-19, the propensity for antigenic imprinting is not difficult to understand.

“The common cold coronaviruses are pretty similar to SARS-CoV2, but they are not exactly the same,” Dr. Spatola said. Her work and studies by others suggest that when antigenic imprinting occurs, “it prevents full maturation of the antibody response.”

NeuroPASC is one of many manifestations of long COVID, but Dr. Spatola pointed out that the immune response in the CSF is unique and the causes of prolonged neurologic impairment after COVID-19 are likely to involve different mechanisms than other long-COVID symptoms.

“Antibodies in the brain are functionally different,” said Dr. Spatola, noting for example that antibody-directed defenses against viral threats show a greater relative reliance on phagocytosis. This might become important in the development of therapeutics for neurologic symptoms of long COVID.
 

A different phenomenon

The manifestations of neuroPASC are heterogeneous and can include confusion, cognitive dysfunction, headache, encephalitis, and other impairments. Neurologic symptoms occur during acute SARS-CoV2 infections, but neuroPASC appears to be a different phenomenon. These symptoms, which develop after the initial respiratory disease has resolved, were attributed by Dr. Spatola to persistent inflammation that is not necessarily directly related to ongoing infection.

“The reason why some patients develop neuroPASC is unknown, but I think the evidence has pointed to a role for the immune system rather than the virus itself,” Dr. Spatola said.

Currently, neuroPASC is a clinical diagnosis but Dr. Spatola and her coinvestigators are conducting research to identify biomarkers. A viable diagnostic test is not expected imminently. They have identified 150 different features with potential relevance to neuroPASC.

In their comparison of those who did relative to those who did not develop neuroPASC, the initial studies were undertaken 2-4 months after the acute COVID-19 symptoms had resolved. The patients with neuroPASC and those without neurologic sequelae have now been followed for 6-8 months, which Dr. Spatola said was too short to draw firm conclusions about outcomes.
 

An evolving concept

Despite the small sample size of this study, these are “very interesting data” for considering the pathogenesis of neuroPASC, which is “a concept that is still evolving,” according to Natalia S. Rost, MD, chief of the stroke division, department of neurology, Massachusetts General Hospital, Boston.

Applied to SARS-CoV2, the concept of original antigenic sin “is new” but Dr. Rost said that it might help differentiate neuroPASC from acute neurologic symptoms of COVID-19, which include stroke. She indicated that the work performed by Dr. Spatola and others might eventually explain the pathology while leading to treatment strategies. She cautioned that the concepts explored in this study “need to be further developed” through larger sample sizes and the exploration of other variables that support the hypothesis.

Dr. Spatola and Dr. Rost report no potential conflicts of interest.

BOSTON – The neurologic symptoms of long COVID appear to be explained by a phenomenon known as antigenic imprinting, which involves a misdirected immune response to the SARS-CoV2 virus, according to a collaborative study presented at the 2023 annual meeting of the American Academy of Neurology.

Already documented in several other viral infections, such as influenza and human immunodeficiency virus, antigenic imprinting results in production of antibodies to previously encountered viral infections rather than to the immediate threat, according to Marianna Spatola, MD, PhD, a research fellow at the Ragon Institute, Harvard University, Cambridge, Mass.
 

Original antigenic sin

In the case of persistent neurologic symptoms after COVID, a condition known as neuroPASC (neurological postacute sequelae of SARS-CoV2 infection), antibodies produced for previously encountered coronaviruses rather than for SARS-CoV2 might explain most or all cases, according to the data Dr. Spatola presented.

The evidence for this explanation was drawn from a study of 112 patients evaluated months after an acute episode of COVID-19. Of these, 18 patients had persistent neurologic dysfunction. When compared with the 94 whose infection resolved without sequelae, the patients with prolonged neurologic impairments had relatively low systemic antibody response to SARS-CoV2. However, they showed relatively high antibody responses against other coronaviruses.

This is a pattern consistent with antigenic imprinting, a concept first described more than 60 years ago as original antigenic sin. When the immune system becomes imprinted with an antigen from the first encountered virus from a family of pathogens, it governs all subsequent antibody responses, according to several published studies that have described and evaluated this concept.
 

Additional evidence

In Dr. Spatola’s study, other differences, particularly in regard to the cerebrospinal fluid (CSF), further supported the role of antigenic imprinting as a cause of neuroPASC. For one, those with elevated immune responses to other common coronaviruses rather than SARS-CoV2 in the CSF relative to the periphery were more likely to have a bad outcome in regard to neurologic symptoms.

Moreover, the CSF in neuroPASC patients “was characterized by increased IgG1 and absence of IgM, suggesting compartmentalized humoral responses within the CSF through selective transfer of antibodies from the serum to the CSF across the blood-brain barrier rather than through intrathecal synthesis,” Dr. Spatola reported.

In the case of COVID-19, the propensity for antigenic imprinting is not difficult to understand.

“The common cold coronaviruses are pretty similar to SARS-CoV2, but they are not exactly the same,” Dr. Spatola said. Her work and studies by others suggest that when antigenic imprinting occurs, “it prevents full maturation of the antibody response.”

NeuroPASC is one of many manifestations of long COVID, but Dr. Spatola pointed out that the immune response in the CSF is unique and the causes of prolonged neurologic impairment after COVID-19 are likely to involve different mechanisms than other long-COVID symptoms.

“Antibodies in the brain are functionally different,” said Dr. Spatola, noting for example that antibody-directed defenses against viral threats show a greater relative reliance on phagocytosis. This might become important in the development of therapeutics for neurologic symptoms of long COVID.
 

A different phenomenon

The manifestations of neuroPASC are heterogeneous and can include confusion, cognitive dysfunction, headache, encephalitis, and other impairments. Neurologic symptoms occur during acute SARS-CoV2 infections, but neuroPASC appears to be a different phenomenon. These symptoms, which develop after the initial respiratory disease has resolved, were attributed by Dr. Spatola to persistent inflammation that is not necessarily directly related to ongoing infection.

“The reason why some patients develop neuroPASC is unknown, but I think the evidence has pointed to a role for the immune system rather than the virus itself,” Dr. Spatola said.

Currently, neuroPASC is a clinical diagnosis but Dr. Spatola and her coinvestigators are conducting research to identify biomarkers. A viable diagnostic test is not expected imminently. They have identified 150 different features with potential relevance to neuroPASC.

In their comparison of those who did relative to those who did not develop neuroPASC, the initial studies were undertaken 2-4 months after the acute COVID-19 symptoms had resolved. The patients with neuroPASC and those without neurologic sequelae have now been followed for 6-8 months, which Dr. Spatola said was too short to draw firm conclusions about outcomes.
 

An evolving concept

Despite the small sample size of this study, these are “very interesting data” for considering the pathogenesis of neuroPASC, which is “a concept that is still evolving,” according to Natalia S. Rost, MD, chief of the stroke division, department of neurology, Massachusetts General Hospital, Boston.

Applied to SARS-CoV2, the concept of original antigenic sin “is new” but Dr. Rost said that it might help differentiate neuroPASC from acute neurologic symptoms of COVID-19, which include stroke. She indicated that the work performed by Dr. Spatola and others might eventually explain the pathology while leading to treatment strategies. She cautioned that the concepts explored in this study “need to be further developed” through larger sample sizes and the exploration of other variables that support the hypothesis.

Dr. Spatola and Dr. Rost report no potential conflicts of interest.

BOSTON – The neurologic symptoms of long COVID appear to be explained by a phenomenon known as antigenic imprinting, which involves a misdirected immune response to the SARS-CoV2 virus, according to a collaborative study presented at the 2023 annual meeting of the American Academy of Neurology.

Already documented in several other viral infections, such as influenza and human immunodeficiency virus, antigenic imprinting results in production of antibodies to previously encountered viral infections rather than to the immediate threat, according to Marianna Spatola, MD, PhD, a research fellow at the Ragon Institute, Harvard University, Cambridge, Mass.
 

Original antigenic sin

In the case of persistent neurologic symptoms after COVID, a condition known as neuroPASC (neurological postacute sequelae of SARS-CoV2 infection), antibodies produced for previously encountered coronaviruses rather than for SARS-CoV2 might explain most or all cases, according to the data Dr. Spatola presented.

The evidence for this explanation was drawn from a study of 112 patients evaluated months after an acute episode of COVID-19. Of these, 18 patients had persistent neurologic dysfunction. When compared with the 94 whose infection resolved without sequelae, the patients with prolonged neurologic impairments had relatively low systemic antibody response to SARS-CoV2. However, they showed relatively high antibody responses against other coronaviruses.

This is a pattern consistent with antigenic imprinting, a concept first described more than 60 years ago as original antigenic sin. When the immune system becomes imprinted with an antigen from the first encountered virus from a family of pathogens, it governs all subsequent antibody responses, according to several published studies that have described and evaluated this concept.
 

Additional evidence

In Dr. Spatola’s study, other differences, particularly in regard to the cerebrospinal fluid (CSF), further supported the role of antigenic imprinting as a cause of neuroPASC. For one, those with elevated immune responses to other common coronaviruses rather than SARS-CoV2 in the CSF relative to the periphery were more likely to have a bad outcome in regard to neurologic symptoms.

Moreover, the CSF in neuroPASC patients “was characterized by increased IgG1 and absence of IgM, suggesting compartmentalized humoral responses within the CSF through selective transfer of antibodies from the serum to the CSF across the blood-brain barrier rather than through intrathecal synthesis,” Dr. Spatola reported.

In the case of COVID-19, the propensity for antigenic imprinting is not difficult to understand.

“The common cold coronaviruses are pretty similar to SARS-CoV2, but they are not exactly the same,” Dr. Spatola said. Her work and studies by others suggest that when antigenic imprinting occurs, “it prevents full maturation of the antibody response.”

NeuroPASC is one of many manifestations of long COVID, but Dr. Spatola pointed out that the immune response in the CSF is unique and the causes of prolonged neurologic impairment after COVID-19 are likely to involve different mechanisms than other long-COVID symptoms.

“Antibodies in the brain are functionally different,” said Dr. Spatola, noting for example that antibody-directed defenses against viral threats show a greater relative reliance on phagocytosis. This might become important in the development of therapeutics for neurologic symptoms of long COVID.
 

A different phenomenon

The manifestations of neuroPASC are heterogeneous and can include confusion, cognitive dysfunction, headache, encephalitis, and other impairments. Neurologic symptoms occur during acute SARS-CoV2 infections, but neuroPASC appears to be a different phenomenon. These symptoms, which develop after the initial respiratory disease has resolved, were attributed by Dr. Spatola to persistent inflammation that is not necessarily directly related to ongoing infection.

“The reason why some patients develop neuroPASC is unknown, but I think the evidence has pointed to a role for the immune system rather than the virus itself,” Dr. Spatola said.

Currently, neuroPASC is a clinical diagnosis but Dr. Spatola and her coinvestigators are conducting research to identify biomarkers. A viable diagnostic test is not expected imminently. They have identified 150 different features with potential relevance to neuroPASC.

In their comparison of those who did relative to those who did not develop neuroPASC, the initial studies were undertaken 2-4 months after the acute COVID-19 symptoms had resolved. The patients with neuroPASC and those without neurologic sequelae have now been followed for 6-8 months, which Dr. Spatola said was too short to draw firm conclusions about outcomes.
 

An evolving concept

Despite the small sample size of this study, these are “very interesting data” for considering the pathogenesis of neuroPASC, which is “a concept that is still evolving,” according to Natalia S. Rost, MD, chief of the stroke division, department of neurology, Massachusetts General Hospital, Boston.

Applied to SARS-CoV2, the concept of original antigenic sin “is new” but Dr. Rost said that it might help differentiate neuroPASC from acute neurologic symptoms of COVID-19, which include stroke. She indicated that the work performed by Dr. Spatola and others might eventually explain the pathology while leading to treatment strategies. She cautioned that the concepts explored in this study “need to be further developed” through larger sample sizes and the exploration of other variables that support the hypothesis.

Dr. Spatola and Dr. Rost report no potential conflicts of interest.

PHOENIX – Of the federal and state malpractice lawsuits filed against dermatologists between 2011 and 2022, half were related to accidental injury, followed by incorrect or delayed diagnoses, and the defendants were more likely to be male.

Those are among key findings from a study that aimed to determine the reasons patients pursue litigation against dermatologists.

“The number of lawsuits against physicians continues to climb annually,” Young Lim, MD, PhD, said at the annual conference of the American Society for Laser Medicine and Surgery, where the results were presented during an abstract session. “Depending on the study, anywhere between 75 to 99 percent of physicians will face a lawsuit by age 65. A clear understanding of prior litigations will help mitigate similar errors in future practice and promote safer, higher quality care.”

Dr. Lim, a dermatology resident at Massachusetts General Hospital and Harvard Medical School, Boston, along with Mathew M. Avram, MD, JD, director of laser, cosmetics, and dermatologic surgery at MGH, and H. Ray Jalian, MD, a cosmetic dermatologist who practices in Los Angeles, used two large national database repositories, WestlawNext and LexisNexis, to retrospectively analyze legal documents following a query using “dermatology” and “dermatologist” as search terms to capture all variety of litigations. They excluded cases in which litigation did not involve patient care as well as those in which the dermatologist was the plaintiff and those in which the dermatologist was involved as a third party.

The final analysis consisted of 54 claims, comprising 43 state and 11 federal cases. Of the 54 cases, 35 involved a male defendant, 12 involved a female defendant, and 7 cases either did not specify the gender of the defendant or involved multiple defendants. Of the 35 cases involving a male defendant, 23 (66%) were brought by female plaintiffs.

Most cases (49, or 91%) involved a defendant dermatologist in private practice while the remaining 5 involved a defendant dermatologist in an academic setting.

The most common reason for litigation was accidental injury (27 cases, or 50%), followed by incorrect or delayed diagnoses (22 cases, or 41%). Five cases resulted from the dermatologist failing to communicate important information, such as postop care instructions or obtaining informed consent.

Of all 54 cases 30 (56%) were dismissed prior to trial, while 24 (44%) resulted in a judgment for the plaintiff. According to Dr. Lim, payout information was available for only five cases, and ranged from $15,000 (injury from laser) to $1,950,000 (delayed diagnosis of malignant melanoma).

“While lawsuits from patients against dermatologists largely involve injury from elective procedures, clinicians should practice caution regarding missed or delayed diagnoses when practicing medical dermatology,” the authors concluded in their abstract. “Ensuring that critical information is shared with patients and obtaining proper written consent will also safeguard against easily-avoidable litigations.”

Christopher B. Zachary, MBBS, professor and chair emeritus of the department of dermatology at the University of California, Irvine, who was asked to comment on the study, said that the findings are a reminder that lack of attention to the most simply performed aspects of care can be the reasons patients will seek medical malpractice redress.

“Consent requires careful and thoughtful explanation of a planned procedure, which should then be recorded in the chart to avoid future confusion,” Dr. Zachary told this news organization. “A patient’s signature on a consent form obtained by a staff member is clearly inadequate if not accompanied by a clear and understandable preoperative discussion. Words, images, video are all elements that aid patients’ comprehension of a planned procedure. And postoperative instructions given to the patients while on the laser table are commonly forgotten by the patient and must be accompanied by written advice summary. Patients will frequently misremember instructions and can be overwhelmed by medical jargon.”

Neither the researchers nor Dr. Zachary reported having relevant financial disclosures.

PHOENIX – Of the federal and state malpractice lawsuits filed against dermatologists between 2011 and 2022, half were related to accidental injury, followed by incorrect or delayed diagnoses, and the defendants were more likely to be male.

Those are among key findings from a study that aimed to determine the reasons patients pursue litigation against dermatologists.

“The number of lawsuits against physicians continues to climb annually,” Young Lim, MD, PhD, said at the annual conference of the American Society for Laser Medicine and Surgery, where the results were presented during an abstract session. “Depending on the study, anywhere between 75 to 99 percent of physicians will face a lawsuit by age 65. A clear understanding of prior litigations will help mitigate similar errors in future practice and promote safer, higher quality care.”

Dr. Lim, a dermatology resident at Massachusetts General Hospital and Harvard Medical School, Boston, along with Mathew M. Avram, MD, JD, director of laser, cosmetics, and dermatologic surgery at MGH, and H. Ray Jalian, MD, a cosmetic dermatologist who practices in Los Angeles, used two large national database repositories, WestlawNext and LexisNexis, to retrospectively analyze legal documents following a query using “dermatology” and “dermatologist” as search terms to capture all variety of litigations. They excluded cases in which litigation did not involve patient care as well as those in which the dermatologist was the plaintiff and those in which the dermatologist was involved as a third party.

The final analysis consisted of 54 claims, comprising 43 state and 11 federal cases. Of the 54 cases, 35 involved a male defendant, 12 involved a female defendant, and 7 cases either did not specify the gender of the defendant or involved multiple defendants. Of the 35 cases involving a male defendant, 23 (66%) were brought by female plaintiffs.

Most cases (49, or 91%) involved a defendant dermatologist in private practice while the remaining 5 involved a defendant dermatologist in an academic setting.

The most common reason for litigation was accidental injury (27 cases, or 50%), followed by incorrect or delayed diagnoses (22 cases, or 41%). Five cases resulted from the dermatologist failing to communicate important information, such as postop care instructions or obtaining informed consent.

Of all 54 cases 30 (56%) were dismissed prior to trial, while 24 (44%) resulted in a judgment for the plaintiff. According to Dr. Lim, payout information was available for only five cases, and ranged from $15,000 (injury from laser) to $1,950,000 (delayed diagnosis of malignant melanoma).

“While lawsuits from patients against dermatologists largely involve injury from elective procedures, clinicians should practice caution regarding missed or delayed diagnoses when practicing medical dermatology,” the authors concluded in their abstract. “Ensuring that critical information is shared with patients and obtaining proper written consent will also safeguard against easily-avoidable litigations.”

Christopher B. Zachary, MBBS, professor and chair emeritus of the department of dermatology at the University of California, Irvine, who was asked to comment on the study, said that the findings are a reminder that lack of attention to the most simply performed aspects of care can be the reasons patients will seek medical malpractice redress.

“Consent requires careful and thoughtful explanation of a planned procedure, which should then be recorded in the chart to avoid future confusion,” Dr. Zachary told this news organization. “A patient’s signature on a consent form obtained by a staff member is clearly inadequate if not accompanied by a clear and understandable preoperative discussion. Words, images, video are all elements that aid patients’ comprehension of a planned procedure. And postoperative instructions given to the patients while on the laser table are commonly forgotten by the patient and must be accompanied by written advice summary. Patients will frequently misremember instructions and can be overwhelmed by medical jargon.”

Neither the researchers nor Dr. Zachary reported having relevant financial disclosures.

PHOENIX – Of the federal and state malpractice lawsuits filed against dermatologists between 2011 and 2022, half were related to accidental injury, followed by incorrect or delayed diagnoses, and the defendants were more likely to be male.

Those are among key findings from a study that aimed to determine the reasons patients pursue litigation against dermatologists.

“The number of lawsuits against physicians continues to climb annually,” Young Lim, MD, PhD, said at the annual conference of the American Society for Laser Medicine and Surgery, where the results were presented during an abstract session. “Depending on the study, anywhere between 75 to 99 percent of physicians will face a lawsuit by age 65. A clear understanding of prior litigations will help mitigate similar errors in future practice and promote safer, higher quality care.”

Dr. Lim, a dermatology resident at Massachusetts General Hospital and Harvard Medical School, Boston, along with Mathew M. Avram, MD, JD, director of laser, cosmetics, and dermatologic surgery at MGH, and H. Ray Jalian, MD, a cosmetic dermatologist who practices in Los Angeles, used two large national database repositories, WestlawNext and LexisNexis, to retrospectively analyze legal documents following a query using “dermatology” and “dermatologist” as search terms to capture all variety of litigations. They excluded cases in which litigation did not involve patient care as well as those in which the dermatologist was the plaintiff and those in which the dermatologist was involved as a third party.

The final analysis consisted of 54 claims, comprising 43 state and 11 federal cases. Of the 54 cases, 35 involved a male defendant, 12 involved a female defendant, and 7 cases either did not specify the gender of the defendant or involved multiple defendants. Of the 35 cases involving a male defendant, 23 (66%) were brought by female plaintiffs.

Most cases (49, or 91%) involved a defendant dermatologist in private practice while the remaining 5 involved a defendant dermatologist in an academic setting.

The most common reason for litigation was accidental injury (27 cases, or 50%), followed by incorrect or delayed diagnoses (22 cases, or 41%). Five cases resulted from the dermatologist failing to communicate important information, such as postop care instructions or obtaining informed consent.

Of all 54 cases 30 (56%) were dismissed prior to trial, while 24 (44%) resulted in a judgment for the plaintiff. According to Dr. Lim, payout information was available for only five cases, and ranged from $15,000 (injury from laser) to $1,950,000 (delayed diagnosis of malignant melanoma).

“While lawsuits from patients against dermatologists largely involve injury from elective procedures, clinicians should practice caution regarding missed or delayed diagnoses when practicing medical dermatology,” the authors concluded in their abstract. “Ensuring that critical information is shared with patients and obtaining proper written consent will also safeguard against easily-avoidable litigations.”

Christopher B. Zachary, MBBS, professor and chair emeritus of the department of dermatology at the University of California, Irvine, who was asked to comment on the study, said that the findings are a reminder that lack of attention to the most simply performed aspects of care can be the reasons patients will seek medical malpractice redress.

“Consent requires careful and thoughtful explanation of a planned procedure, which should then be recorded in the chart to avoid future confusion,” Dr. Zachary told this news organization. “A patient’s signature on a consent form obtained by a staff member is clearly inadequate if not accompanied by a clear and understandable preoperative discussion. Words, images, video are all elements that aid patients’ comprehension of a planned procedure. And postoperative instructions given to the patients while on the laser table are commonly forgotten by the patient and must be accompanied by written advice summary. Patients will frequently misremember instructions and can be overwhelmed by medical jargon.”

Neither the researchers nor Dr. Zachary reported having relevant financial disclosures.

The American College of Cardiology has released an Expert Consensus Decision Pathway (ECDP) on the management of heart failure with preserved ejection fraction (HFpEF).

The 44-page document highlights the “critical need” to accurately diagnose HFpEF to permit timely implementation of evidence- and guideline-based therapies to improve patient outcomes.

Although the incidence of overall HF in the United States appears to be stable or declining, the incidence of HFpEF continues to rise in tandem with increasing age and burdens of obesity, sedentary lifestyle, and cardiometabolic disorders.

HFpEF now accounts for more than one half of HF cases but remains “underrecognized” in everyday clinical practice, said the writing group, led by Michelle Kittleson, MD, PhD, professor of medicine, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles.

HFpEF is a complex condition, often with multiple overlapping comorbidities, including hypertension, diabetes, obesity, and sleep apnea; optimal management requires a multidisciplinary approach, the writing group said.

The ECDP on HFpEF lays out a structure for diagnosis, clinical decision-making, management of comorbidities, implementation of the latest guideline-directed medical therapy (pharmacologic and nonpharmacologic), and equitable delivery of care.

The document was published online in the Journal of the American College of Cardiology.

It aligns with and builds on recommendations from the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure.

“HFpEF is one of the most pressing diagnostic and therapeutic challenges in clinical medicine today given its increasing prevalence, under diagnosis, poor prognosis, limited therapeutic options, and substantial burden on the health care system worldwide,” wrote the authors of a companion scientific statement on HFpEF.

Despite these challenges, the success of recent sodium-glucose cotransporter 2 inhibitor trials has shown that HFpEF is treatable, Barry Borlaug, MD, department of cardiovascular medicine, Mayo Clinic, Rochester, Minn., and coauthors pointed out.

They noted that “ongoing large-scale studies of HFpEF pathobiology, an increasing number of translational studies spanning the gap between the bedside and the bench, and numerous clinical trials of novel therapeutics in HFpEF offer a glimpse of hope toward a future of reduced prevalence, morbidity, and mortality associated with HFpEF, which would be a major advance for population health.”

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

The American College of Cardiology has released an Expert Consensus Decision Pathway (ECDP) on the management of heart failure with preserved ejection fraction (HFpEF).

The 44-page document highlights the “critical need” to accurately diagnose HFpEF to permit timely implementation of evidence- and guideline-based therapies to improve patient outcomes.

Although the incidence of overall HF in the United States appears to be stable or declining, the incidence of HFpEF continues to rise in tandem with increasing age and burdens of obesity, sedentary lifestyle, and cardiometabolic disorders.

HFpEF now accounts for more than one half of HF cases but remains “underrecognized” in everyday clinical practice, said the writing group, led by Michelle Kittleson, MD, PhD, professor of medicine, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles.

HFpEF is a complex condition, often with multiple overlapping comorbidities, including hypertension, diabetes, obesity, and sleep apnea; optimal management requires a multidisciplinary approach, the writing group said.

The ECDP on HFpEF lays out a structure for diagnosis, clinical decision-making, management of comorbidities, implementation of the latest guideline-directed medical therapy (pharmacologic and nonpharmacologic), and equitable delivery of care.

The document was published online in the Journal of the American College of Cardiology.

It aligns with and builds on recommendations from the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure.

“HFpEF is one of the most pressing diagnostic and therapeutic challenges in clinical medicine today given its increasing prevalence, under diagnosis, poor prognosis, limited therapeutic options, and substantial burden on the health care system worldwide,” wrote the authors of a companion scientific statement on HFpEF.

Despite these challenges, the success of recent sodium-glucose cotransporter 2 inhibitor trials has shown that HFpEF is treatable, Barry Borlaug, MD, department of cardiovascular medicine, Mayo Clinic, Rochester, Minn., and coauthors pointed out.

They noted that “ongoing large-scale studies of HFpEF pathobiology, an increasing number of translational studies spanning the gap between the bedside and the bench, and numerous clinical trials of novel therapeutics in HFpEF offer a glimpse of hope toward a future of reduced prevalence, morbidity, and mortality associated with HFpEF, which would be a major advance for population health.”

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

The American College of Cardiology has released an Expert Consensus Decision Pathway (ECDP) on the management of heart failure with preserved ejection fraction (HFpEF).

The 44-page document highlights the “critical need” to accurately diagnose HFpEF to permit timely implementation of evidence- and guideline-based therapies to improve patient outcomes.

Although the incidence of overall HF in the United States appears to be stable or declining, the incidence of HFpEF continues to rise in tandem with increasing age and burdens of obesity, sedentary lifestyle, and cardiometabolic disorders.

HFpEF now accounts for more than one half of HF cases but remains “underrecognized” in everyday clinical practice, said the writing group, led by Michelle Kittleson, MD, PhD, professor of medicine, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles.

HFpEF is a complex condition, often with multiple overlapping comorbidities, including hypertension, diabetes, obesity, and sleep apnea; optimal management requires a multidisciplinary approach, the writing group said.

The ECDP on HFpEF lays out a structure for diagnosis, clinical decision-making, management of comorbidities, implementation of the latest guideline-directed medical therapy (pharmacologic and nonpharmacologic), and equitable delivery of care.

The document was published online in the Journal of the American College of Cardiology.

It aligns with and builds on recommendations from the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure.

“HFpEF is one of the most pressing diagnostic and therapeutic challenges in clinical medicine today given its increasing prevalence, under diagnosis, poor prognosis, limited therapeutic options, and substantial burden on the health care system worldwide,” wrote the authors of a companion scientific statement on HFpEF.

Despite these challenges, the success of recent sodium-glucose cotransporter 2 inhibitor trials has shown that HFpEF is treatable, Barry Borlaug, MD, department of cardiovascular medicine, Mayo Clinic, Rochester, Minn., and coauthors pointed out.

They noted that “ongoing large-scale studies of HFpEF pathobiology, an increasing number of translational studies spanning the gap between the bedside and the bench, and numerous clinical trials of novel therapeutics in HFpEF offer a glimpse of hope toward a future of reduced prevalence, morbidity, and mortality associated with HFpEF, which would be a major advance for population health.”

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

Last week, unbeknownst to most people, Dayton, Ohio, hosted the world championships of Winter Drumline. It’s a combination of percussion instruments, dance, and music, with a storyline. Think of it as a very fast-paced half-time show, with only percussion, in 6 minutes or less.

My daughter fell in love with it her second year of high school, and has participated in it through college. Her specialty is the pit – marimba, vibraphone, xylophone. This gives our house a cruise ship atmosphere when she comes home to practice on weekends.

Over the years my wife and I have gone to many of her shows and competitions, streamed others online, and always been amazed by the variety of costumes, choreography, music numbers, and overall themes different teams come up with. We’ve seen shows based on 1930s detective fiction, ocean life, westerns, science fiction, toxic waste, emotions, relationships, flamenco, pirate ships, and many others.

And, as always, I marvel at the human brain.

Only 2-3 pounds but still an amazing thing. The capacity for imagination is endless, and one of the things that got us where we are today. The ability to see things that don’t exist yet, and work out the details on how to get there. The pyramids, Petra, the Great Wall, flight, the steam engine, landing on the moon, the ISS. And, of course, Winter Drumline.

It’s a uniquely (as far as we know) human capacity. To look at a rock and envision what it might be carved into. To look at Jupiter and think of a way to get a probe there. To sit in an empty gym and imagine the floor covered with dozens of percussion instruments and their players, imagining what each will be playing and doing at a given moment.

It’s really a remarkable capacity when you think about it. I’m sure it originally began as a way to figure out where you might find shelter or food, or simply to outwit the other tribe. But it’s become so much more than that. Someone envisioned every movie you see, book you read, and the computer I’m writing this on.

In his 1968 novelization of “2001: A Space Odyssey” Arthur C. Clarke described the thoughts of the unknown civilization that had left the Monolith behind for us as “in all the galaxy they had found nothing more precious than Mind.”

I’d agree with that. Even after 30 years of learning about the 2-3 pounds of semi-solid tissue we all carry upstairs, and doing my best to treat its malfunctions, I’ve never ceased to be amazed by it.

I hope I always will be.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Last week, unbeknownst to most people, Dayton, Ohio, hosted the world championships of Winter Drumline. It’s a combination of percussion instruments, dance, and music, with a storyline. Think of it as a very fast-paced half-time show, with only percussion, in 6 minutes or less.

My daughter fell in love with it her second year of high school, and has participated in it through college. Her specialty is the pit – marimba, vibraphone, xylophone. This gives our house a cruise ship atmosphere when she comes home to practice on weekends.

Over the years my wife and I have gone to many of her shows and competitions, streamed others online, and always been amazed by the variety of costumes, choreography, music numbers, and overall themes different teams come up with. We’ve seen shows based on 1930s detective fiction, ocean life, westerns, science fiction, toxic waste, emotions, relationships, flamenco, pirate ships, and many others.

And, as always, I marvel at the human brain.

Only 2-3 pounds but still an amazing thing. The capacity for imagination is endless, and one of the things that got us where we are today. The ability to see things that don’t exist yet, and work out the details on how to get there. The pyramids, Petra, the Great Wall, flight, the steam engine, landing on the moon, the ISS. And, of course, Winter Drumline.

It’s a uniquely (as far as we know) human capacity. To look at a rock and envision what it might be carved into. To look at Jupiter and think of a way to get a probe there. To sit in an empty gym and imagine the floor covered with dozens of percussion instruments and their players, imagining what each will be playing and doing at a given moment.

It’s really a remarkable capacity when you think about it. I’m sure it originally began as a way to figure out where you might find shelter or food, or simply to outwit the other tribe. But it’s become so much more than that. Someone envisioned every movie you see, book you read, and the computer I’m writing this on.

In his 1968 novelization of “2001: A Space Odyssey” Arthur C. Clarke described the thoughts of the unknown civilization that had left the Monolith behind for us as “in all the galaxy they had found nothing more precious than Mind.”

I’d agree with that. Even after 30 years of learning about the 2-3 pounds of semi-solid tissue we all carry upstairs, and doing my best to treat its malfunctions, I’ve never ceased to be amazed by it.

I hope I always will be.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Last week, unbeknownst to most people, Dayton, Ohio, hosted the world championships of Winter Drumline. It’s a combination of percussion instruments, dance, and music, with a storyline. Think of it as a very fast-paced half-time show, with only percussion, in 6 minutes or less.

My daughter fell in love with it her second year of high school, and has participated in it through college. Her specialty is the pit – marimba, vibraphone, xylophone. This gives our house a cruise ship atmosphere when she comes home to practice on weekends.

Over the years my wife and I have gone to many of her shows and competitions, streamed others online, and always been amazed by the variety of costumes, choreography, music numbers, and overall themes different teams come up with. We’ve seen shows based on 1930s detective fiction, ocean life, westerns, science fiction, toxic waste, emotions, relationships, flamenco, pirate ships, and many others.

And, as always, I marvel at the human brain.

Only 2-3 pounds but still an amazing thing. The capacity for imagination is endless, and one of the things that got us where we are today. The ability to see things that don’t exist yet, and work out the details on how to get there. The pyramids, Petra, the Great Wall, flight, the steam engine, landing on the moon, the ISS. And, of course, Winter Drumline.

It’s a uniquely (as far as we know) human capacity. To look at a rock and envision what it might be carved into. To look at Jupiter and think of a way to get a probe there. To sit in an empty gym and imagine the floor covered with dozens of percussion instruments and their players, imagining what each will be playing and doing at a given moment.

It’s really a remarkable capacity when you think about it. I’m sure it originally began as a way to figure out where you might find shelter or food, or simply to outwit the other tribe. But it’s become so much more than that. Someone envisioned every movie you see, book you read, and the computer I’m writing this on.

In his 1968 novelization of “2001: A Space Odyssey” Arthur C. Clarke described the thoughts of the unknown civilization that had left the Monolith behind for us as “in all the galaxy they had found nothing more precious than Mind.”

I’d agree with that. Even after 30 years of learning about the 2-3 pounds of semi-solid tissue we all carry upstairs, and doing my best to treat its malfunctions, I’ve never ceased to be amazed by it.

I hope I always will be.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

How old were you when you had your first job? No, not that one when the neighbors paid you to feed their goldfish while they were on vacation. I mean the one when you first saw the dreaded letters “FICA” on your pay stub and realized that “making $9.00 an hour” didn’t mean that you would be taking home $360 at the end of a 40-hour week.

Were you still in middle school or just entering high school? Was it during the summer before you entered college? Was it a positive experience? If not financially, did that job at least provide some life lessons that you have found valuable?

Among my peers in a middle class dominated small town, having a “good” summer job was somewhat of a status symbol. Few of us worked during the school year. Having family connections meant that you might be lucky enough to be hired “doing construction” and making big bucks. Most of our families didn’t “need” the money we earned. Our paychecks provided us with our first taste of what it meant do some “discretionary spending” and build a savings account. And ... it meant we weren’t hanging around the house getting into trouble. As I recall we and our parents saw working as a teenager as a win-win situation.

A recent survey done by investigators at the C.S. Mott Children’s Hospital at the University of Michigan polled parents about their thoughts about teenagers working (Parents see upsides and downsides to teen jobs, Mott Poll Report, April 17, 2023). In reviewing data from the hospital’s National Poll On Children’s Health, the researchers found that parents prioritized whether the job would fit their teens’ schedules (87%), the logistics of getting the teenager to the job (68%), and whether it would provide a learning experience (54%). Only a third listed pay rate as a consideration.

Parents reported half of their 18-year-olds had jobs, 42% aged 16-17 had jobs, and less than 10% of the 14- to 15-year-olds had jobs. Parents of teenagers with jobs felt that the work experience made a positive impact on money management (76%), self-esteem (70%), and time management (63%). On the other hand, a smaller percentage of parents reported a negative effect on sleep (16%), activities (11%), social life (11%), and grades (4%). Forty-four percent of parents of working teenagers reported that their children had experienced problems at work. These included issues of too many or too few hours, disagreements with coworkers or managers, and pay not meeting expectations.

It is interesting that although I can’t provide any data, my impression is that a much higher percentage of my peer group were working when we were younger than 18. Not surprisingly, the teenagers who are currently working distribute their income much as we had done 50 years ago.

How should we as primary care providers interpret the results of this poll? Of course they support my bias or I wouldn’t be sharing them with you. I have found that for most teenagers, a job can have a positive influence on their development and with a modest amount of parental oversight will have a minimal impact on their health and safety. As a result I have asked most teenagers at their health maintenance visits if they have any summer work plans. This survey also demonstrated that parents don’t need to be cautioned about the potential downsides. In fact, they might even benefit from the observation that the upsides of work are considerable.

The fact that nearly half of teenagers experienced workplace problems doesn’t impress me as a downside. It merely reflects reality and provides opportunities for learning and growth. With the unemployment rate at rock bottom, this is an excellent climate for teenagers to dip their toes into the working world. If they feel they are being mistreated on the job they should realize that they are in the driver’s seat. They won’t have to look very far to find a “hiring” sign in another window just down the street.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

How old were you when you had your first job? No, not that one when the neighbors paid you to feed their goldfish while they were on vacation. I mean the one when you first saw the dreaded letters “FICA” on your pay stub and realized that “making $9.00 an hour” didn’t mean that you would be taking home $360 at the end of a 40-hour week.

Were you still in middle school or just entering high school? Was it during the summer before you entered college? Was it a positive experience? If not financially, did that job at least provide some life lessons that you have found valuable?

Among my peers in a middle class dominated small town, having a “good” summer job was somewhat of a status symbol. Few of us worked during the school year. Having family connections meant that you might be lucky enough to be hired “doing construction” and making big bucks. Most of our families didn’t “need” the money we earned. Our paychecks provided us with our first taste of what it meant do some “discretionary spending” and build a savings account. And ... it meant we weren’t hanging around the house getting into trouble. As I recall we and our parents saw working as a teenager as a win-win situation.

A recent survey done by investigators at the C.S. Mott Children’s Hospital at the University of Michigan polled parents about their thoughts about teenagers working (Parents see upsides and downsides to teen jobs, Mott Poll Report, April 17, 2023). In reviewing data from the hospital’s National Poll On Children’s Health, the researchers found that parents prioritized whether the job would fit their teens’ schedules (87%), the logistics of getting the teenager to the job (68%), and whether it would provide a learning experience (54%). Only a third listed pay rate as a consideration.

Parents reported half of their 18-year-olds had jobs, 42% aged 16-17 had jobs, and less than 10% of the 14- to 15-year-olds had jobs. Parents of teenagers with jobs felt that the work experience made a positive impact on money management (76%), self-esteem (70%), and time management (63%). On the other hand, a smaller percentage of parents reported a negative effect on sleep (16%), activities (11%), social life (11%), and grades (4%). Forty-four percent of parents of working teenagers reported that their children had experienced problems at work. These included issues of too many or too few hours, disagreements with coworkers or managers, and pay not meeting expectations.

It is interesting that although I can’t provide any data, my impression is that a much higher percentage of my peer group were working when we were younger than 18. Not surprisingly, the teenagers who are currently working distribute their income much as we had done 50 years ago.

How should we as primary care providers interpret the results of this poll? Of course they support my bias or I wouldn’t be sharing them with you. I have found that for most teenagers, a job can have a positive influence on their development and with a modest amount of parental oversight will have a minimal impact on their health and safety. As a result I have asked most teenagers at their health maintenance visits if they have any summer work plans. This survey also demonstrated that parents don’t need to be cautioned about the potential downsides. In fact, they might even benefit from the observation that the upsides of work are considerable.

The fact that nearly half of teenagers experienced workplace problems doesn’t impress me as a downside. It merely reflects reality and provides opportunities for learning and growth. With the unemployment rate at rock bottom, this is an excellent climate for teenagers to dip their toes into the working world. If they feel they are being mistreated on the job they should realize that they are in the driver’s seat. They won’t have to look very far to find a “hiring” sign in another window just down the street.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

How old were you when you had your first job? No, not that one when the neighbors paid you to feed their goldfish while they were on vacation. I mean the one when you first saw the dreaded letters “FICA” on your pay stub and realized that “making $9.00 an hour” didn’t mean that you would be taking home $360 at the end of a 40-hour week.

Were you still in middle school or just entering high school? Was it during the summer before you entered college? Was it a positive experience? If not financially, did that job at least provide some life lessons that you have found valuable?

Among my peers in a middle class dominated small town, having a “good” summer job was somewhat of a status symbol. Few of us worked during the school year. Having family connections meant that you might be lucky enough to be hired “doing construction” and making big bucks. Most of our families didn’t “need” the money we earned. Our paychecks provided us with our first taste of what it meant do some “discretionary spending” and build a savings account. And ... it meant we weren’t hanging around the house getting into trouble. As I recall we and our parents saw working as a teenager as a win-win situation.

A recent survey done by investigators at the C.S. Mott Children’s Hospital at the University of Michigan polled parents about their thoughts about teenagers working (Parents see upsides and downsides to teen jobs, Mott Poll Report, April 17, 2023). In reviewing data from the hospital’s National Poll On Children’s Health, the researchers found that parents prioritized whether the job would fit their teens’ schedules (87%), the logistics of getting the teenager to the job (68%), and whether it would provide a learning experience (54%). Only a third listed pay rate as a consideration.

Parents reported half of their 18-year-olds had jobs, 42% aged 16-17 had jobs, and less than 10% of the 14- to 15-year-olds had jobs. Parents of teenagers with jobs felt that the work experience made a positive impact on money management (76%), self-esteem (70%), and time management (63%). On the other hand, a smaller percentage of parents reported a negative effect on sleep (16%), activities (11%), social life (11%), and grades (4%). Forty-four percent of parents of working teenagers reported that their children had experienced problems at work. These included issues of too many or too few hours, disagreements with coworkers or managers, and pay not meeting expectations.

It is interesting that although I can’t provide any data, my impression is that a much higher percentage of my peer group were working when we were younger than 18. Not surprisingly, the teenagers who are currently working distribute their income much as we had done 50 years ago.

How should we as primary care providers interpret the results of this poll? Of course they support my bias or I wouldn’t be sharing them with you. I have found that for most teenagers, a job can have a positive influence on their development and with a modest amount of parental oversight will have a minimal impact on their health and safety. As a result I have asked most teenagers at their health maintenance visits if they have any summer work plans. This survey also demonstrated that parents don’t need to be cautioned about the potential downsides. In fact, they might even benefit from the observation that the upsides of work are considerable.

The fact that nearly half of teenagers experienced workplace problems doesn’t impress me as a downside. It merely reflects reality and provides opportunities for learning and growth. With the unemployment rate at rock bottom, this is an excellent climate for teenagers to dip their toes into the working world. If they feel they are being mistreated on the job they should realize that they are in the driver’s seat. They won’t have to look very far to find a “hiring” sign in another window just down the street.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].