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Best Practices When Using POEM to Treat Achalasia: AGA Clinical Update
The American Gastroenterological Association (AGA) has released
“Any patient suspected to have achalasia, or difficulty swallowing for that matter, should undergo a comprehensive diagnostic workup, and that should include clinical history, review of medication, as well as tests. The diagnosis should not be based on isolated tests but on the clinical picture as a whole,” first author Dennis Yang, MD, AGAF, with the Center for Interventional Endoscopy, AdventHealth, Orlando, Florida, noted in an AGA podcast about the update.
The clinical practice update, published in Gastroenterology, includes 12 “best practice advice” statements.
Since its introduction to clinical practice more than a decade ago, POEM has matured and gained widespread acceptance because of its efficacy and safety profile.
POEM has at least similar outcomes to laparoscopic Heller myotomy and pneumatic dilation for type I and type II achalasia with better results for those with type III achalasia, Yang noted.
“However, besides disease phenotype, we need to remember that choosing the right treatment for the patient is going to be based on multiple factors including patient characteristics as well as local expertise,” Yang added.
In terms of technical considerations, the update states that both anterior and posterior tunnel approaches demonstrate comparable success and postprocedure reflux rates. Tunnel orientation should be tailored to the patient’s surgical history and endoscopist’s preference.
It further states that optimal length of the myotomy in the esophagus and cardia, as it pertains to treatment efficacy and risk for postprocedure reflux, remains to be determined.
Adjunct techniques, including real-time intraprocedure functional luminal impedance planimetry, may be considered to tailor or confirm the adequacy of the myotomy.
Same-day discharge after POEM can be considered in select patients who meet discharge criteria. Patients with advanced age, significant comorbidities, poor social support, and/or access to specialized care should be considered for hospital admission, irrespective of symptoms.
The update notes that specific guidelines on the role and extent of antibiotic prophylaxis before and after POEM are lacking. A single dose of antibiotics at the time of POEM “may be sufficient” for antibiotic prophylaxis.
In terms of immediate post-POEM care, the update notes that the clinical impact of routine esophagram or endoscopy immediately post-POEM remains unclear. Testing can be considered based on local practice preferences and in cases in which intraprocedural events or postprocedural findings warrant further evaluation.
Proton pump inhibitors are recommended immediately following POEM, as gastroesophageal reflux disease (GERD) is common following POEM, occurring in up to 65% of cases.
Routine endoscopic surveillance is advised to monitor GERD, disease progression, and esophageal cancer risk, which is significantly higher in achalasia patients.
“Just like diabetes and hypertension, we need to remember that achalasia is a chronic disease and long-term postprocedural surveillance is strongly encouraged to monitor disease progression as well as potential complications of reflux,” Yang said.
He noted that surveillance should be considered irrespective of patient symptoms because many of these patients may remain asymptomatic.
“Primary gastroenterologists should have a very low threshold in referring the patient back to the POEM endoscopist or any specialized esophageal center because the ideology of symptoms in these patients can be quite difficult to tease out and often require comprehensive diagnostic workup,” Yang said.
Evidence for POEM in esophagogastric outflow obstruction and other nonachalasia spastic motility disorders is limited and should only be considered on a case-by-case basis after other less invasive approaches have been exhausted, the update states.
For perspective on the POEM clinical practice update, this news organization spoke with Mouen Khashab, MD, director of therapeutic endoscopy, Johns Hopkins University, Baltimore, Maryland.
“The document is very well written and comprehensive,” Khashab said.
However, Khashab said he would have liked to see greater emphasis on the value or role of a short myotomy in the esophagus and cardia.
“There is level I evidence that the short esophageal myotomy is equivalent to a long esophageal myotomy for type I and II achalasia. When you do a short myotomy, you save procedure time and there is potentially a lower incidence of blown-out myotomy or BOM,” Khashab said.
Khashab also noted that a long myotomy on the gastric side “likely increases the risk of reflux disease, and therefore a limited myotomy on the gastric side likely also is advantageous.”
This research had no commercial funding. Yang serves as a consultant for Boston Scientific, Olympus, FujiFilm, Microtech, Medtronic, 3D-Matrix, and Neptune Medical, and has received research support from Microtech and 3D-Matrix. Khashab had no relevant disclosures.
A version of this article appeared on Medscape.com .
The American Gastroenterological Association (AGA) has released
“Any patient suspected to have achalasia, or difficulty swallowing for that matter, should undergo a comprehensive diagnostic workup, and that should include clinical history, review of medication, as well as tests. The diagnosis should not be based on isolated tests but on the clinical picture as a whole,” first author Dennis Yang, MD, AGAF, with the Center for Interventional Endoscopy, AdventHealth, Orlando, Florida, noted in an AGA podcast about the update.
The clinical practice update, published in Gastroenterology, includes 12 “best practice advice” statements.
Since its introduction to clinical practice more than a decade ago, POEM has matured and gained widespread acceptance because of its efficacy and safety profile.
POEM has at least similar outcomes to laparoscopic Heller myotomy and pneumatic dilation for type I and type II achalasia with better results for those with type III achalasia, Yang noted.
“However, besides disease phenotype, we need to remember that choosing the right treatment for the patient is going to be based on multiple factors including patient characteristics as well as local expertise,” Yang added.
In terms of technical considerations, the update states that both anterior and posterior tunnel approaches demonstrate comparable success and postprocedure reflux rates. Tunnel orientation should be tailored to the patient’s surgical history and endoscopist’s preference.
It further states that optimal length of the myotomy in the esophagus and cardia, as it pertains to treatment efficacy and risk for postprocedure reflux, remains to be determined.
Adjunct techniques, including real-time intraprocedure functional luminal impedance planimetry, may be considered to tailor or confirm the adequacy of the myotomy.
Same-day discharge after POEM can be considered in select patients who meet discharge criteria. Patients with advanced age, significant comorbidities, poor social support, and/or access to specialized care should be considered for hospital admission, irrespective of symptoms.
The update notes that specific guidelines on the role and extent of antibiotic prophylaxis before and after POEM are lacking. A single dose of antibiotics at the time of POEM “may be sufficient” for antibiotic prophylaxis.
In terms of immediate post-POEM care, the update notes that the clinical impact of routine esophagram or endoscopy immediately post-POEM remains unclear. Testing can be considered based on local practice preferences and in cases in which intraprocedural events or postprocedural findings warrant further evaluation.
Proton pump inhibitors are recommended immediately following POEM, as gastroesophageal reflux disease (GERD) is common following POEM, occurring in up to 65% of cases.
Routine endoscopic surveillance is advised to monitor GERD, disease progression, and esophageal cancer risk, which is significantly higher in achalasia patients.
“Just like diabetes and hypertension, we need to remember that achalasia is a chronic disease and long-term postprocedural surveillance is strongly encouraged to monitor disease progression as well as potential complications of reflux,” Yang said.
He noted that surveillance should be considered irrespective of patient symptoms because many of these patients may remain asymptomatic.
“Primary gastroenterologists should have a very low threshold in referring the patient back to the POEM endoscopist or any specialized esophageal center because the ideology of symptoms in these patients can be quite difficult to tease out and often require comprehensive diagnostic workup,” Yang said.
Evidence for POEM in esophagogastric outflow obstruction and other nonachalasia spastic motility disorders is limited and should only be considered on a case-by-case basis after other less invasive approaches have been exhausted, the update states.
For perspective on the POEM clinical practice update, this news organization spoke with Mouen Khashab, MD, director of therapeutic endoscopy, Johns Hopkins University, Baltimore, Maryland.
“The document is very well written and comprehensive,” Khashab said.
However, Khashab said he would have liked to see greater emphasis on the value or role of a short myotomy in the esophagus and cardia.
“There is level I evidence that the short esophageal myotomy is equivalent to a long esophageal myotomy for type I and II achalasia. When you do a short myotomy, you save procedure time and there is potentially a lower incidence of blown-out myotomy or BOM,” Khashab said.
Khashab also noted that a long myotomy on the gastric side “likely increases the risk of reflux disease, and therefore a limited myotomy on the gastric side likely also is advantageous.”
This research had no commercial funding. Yang serves as a consultant for Boston Scientific, Olympus, FujiFilm, Microtech, Medtronic, 3D-Matrix, and Neptune Medical, and has received research support from Microtech and 3D-Matrix. Khashab had no relevant disclosures.
A version of this article appeared on Medscape.com .
The American Gastroenterological Association (AGA) has released
“Any patient suspected to have achalasia, or difficulty swallowing for that matter, should undergo a comprehensive diagnostic workup, and that should include clinical history, review of medication, as well as tests. The diagnosis should not be based on isolated tests but on the clinical picture as a whole,” first author Dennis Yang, MD, AGAF, with the Center for Interventional Endoscopy, AdventHealth, Orlando, Florida, noted in an AGA podcast about the update.
The clinical practice update, published in Gastroenterology, includes 12 “best practice advice” statements.
Since its introduction to clinical practice more than a decade ago, POEM has matured and gained widespread acceptance because of its efficacy and safety profile.
POEM has at least similar outcomes to laparoscopic Heller myotomy and pneumatic dilation for type I and type II achalasia with better results for those with type III achalasia, Yang noted.
“However, besides disease phenotype, we need to remember that choosing the right treatment for the patient is going to be based on multiple factors including patient characteristics as well as local expertise,” Yang added.
In terms of technical considerations, the update states that both anterior and posterior tunnel approaches demonstrate comparable success and postprocedure reflux rates. Tunnel orientation should be tailored to the patient’s surgical history and endoscopist’s preference.
It further states that optimal length of the myotomy in the esophagus and cardia, as it pertains to treatment efficacy and risk for postprocedure reflux, remains to be determined.
Adjunct techniques, including real-time intraprocedure functional luminal impedance planimetry, may be considered to tailor or confirm the adequacy of the myotomy.
Same-day discharge after POEM can be considered in select patients who meet discharge criteria. Patients with advanced age, significant comorbidities, poor social support, and/or access to specialized care should be considered for hospital admission, irrespective of symptoms.
The update notes that specific guidelines on the role and extent of antibiotic prophylaxis before and after POEM are lacking. A single dose of antibiotics at the time of POEM “may be sufficient” for antibiotic prophylaxis.
In terms of immediate post-POEM care, the update notes that the clinical impact of routine esophagram or endoscopy immediately post-POEM remains unclear. Testing can be considered based on local practice preferences and in cases in which intraprocedural events or postprocedural findings warrant further evaluation.
Proton pump inhibitors are recommended immediately following POEM, as gastroesophageal reflux disease (GERD) is common following POEM, occurring in up to 65% of cases.
Routine endoscopic surveillance is advised to monitor GERD, disease progression, and esophageal cancer risk, which is significantly higher in achalasia patients.
“Just like diabetes and hypertension, we need to remember that achalasia is a chronic disease and long-term postprocedural surveillance is strongly encouraged to monitor disease progression as well as potential complications of reflux,” Yang said.
He noted that surveillance should be considered irrespective of patient symptoms because many of these patients may remain asymptomatic.
“Primary gastroenterologists should have a very low threshold in referring the patient back to the POEM endoscopist or any specialized esophageal center because the ideology of symptoms in these patients can be quite difficult to tease out and often require comprehensive diagnostic workup,” Yang said.
Evidence for POEM in esophagogastric outflow obstruction and other nonachalasia spastic motility disorders is limited and should only be considered on a case-by-case basis after other less invasive approaches have been exhausted, the update states.
For perspective on the POEM clinical practice update, this news organization spoke with Mouen Khashab, MD, director of therapeutic endoscopy, Johns Hopkins University, Baltimore, Maryland.
“The document is very well written and comprehensive,” Khashab said.
However, Khashab said he would have liked to see greater emphasis on the value or role of a short myotomy in the esophagus and cardia.
“There is level I evidence that the short esophageal myotomy is equivalent to a long esophageal myotomy for type I and II achalasia. When you do a short myotomy, you save procedure time and there is potentially a lower incidence of blown-out myotomy or BOM,” Khashab said.
Khashab also noted that a long myotomy on the gastric side “likely increases the risk of reflux disease, and therefore a limited myotomy on the gastric side likely also is advantageous.”
This research had no commercial funding. Yang serves as a consultant for Boston Scientific, Olympus, FujiFilm, Microtech, Medtronic, 3D-Matrix, and Neptune Medical, and has received research support from Microtech and 3D-Matrix. Khashab had no relevant disclosures.
A version of this article appeared on Medscape.com .
FROM GASTROENTEROLOGY
Promise for CAR T-Cell Therapies in Solid Tumors?
Chimeric antigen receptor (CAR) T-cell therapy has shown efficacy in blood cancers — with six CAR T-cell products now approved by the Food and Drug Administration (FDA) to treat six hematologic malignancies.
For solid tumors, however, the efficacy of CAR T-cell treatments has been limited and progress “more incremental,” Christian Hinrichs, MD, with Rutgers Cancer Institute in New Brunswick, New Jersey, told this news organization. Currently, there are no CAR T-cell therapies approved in the United States to treat solid tumors.
Why have CAR T-cell therapies been less effective against solid tumors?
Perhaps the biggest hurdle is the ability to identify and selectively target specific molecular structures in cancer cells without causing severe toxicity by injuring healthy cells, Hinrichs and coauthors wrote in a recent JAMA review.
CAR T-cells are made up of “T cells genetically engineered to express a synthetic receptor that recognizes a tumor cell-surface protein,” Hinrichs and colleagues explained. But identifying cell surface antigens that are exclusive to solid tumor cells has been a challenge, which means CAR T-cell therapies end up affecting both tumor and healthy tissues.
“This makes it difficult to target and kill all the tumor cells without causing severe toxicity from injury to healthy cells,” Hinrichs explained.
Other common obstacles include challenges penetrating the dense extracellular matrix of solid tumors and the need to overcome inhibitory cells and molecules in the tumor microenvironment.
Despite the challenges and slow progress, some “promising results” have begun to emerge in the solid tumor, CAR T-cell space, Hinrichs said.
A recent phase 1-2 study, for instance, found that 63% (17 of 27) of pediatric patients with heavily pretreated neuroblastoma achieved an overall response with an investigational CAR T-cell therapy, GD2-CART01.
In a recent phase 1 trial, 38 of 98 patients with gastrointestinal cancers (39%) achieved partial or complete responses after receiving an investigational CAR T-cell treatment directed at Claudin18.2. However, the responses were short overall and could have been related to the chemotherapy given before the CAR T-cell infusion.
Another phase 1 trial found that a GPC3-targeted CAR T-cell therapy led to an objective response rate in half (12 of 24) of heavily treated patients with advanced hepatocellular carcinoma, with a disease control rate of almost 91%.
Outside of CAR-T cell therapies, other cell-based treatments have shown promise against solid tumors, including two T-cell therapies recently approved by the FDA.
Last February, the FDA approved the tumor-infiltrating lymphocyte (TIL) therapy lifileucel (Amtagvi) for advanced melanoma. In August, the agency approved the T-cell receptor (TCR) therapy afamitresgene autoleucel for advanced synovial sarcoma.
“Response rates for these cellular therapies are in the 30% range, but already there is clear data that there’s durability for some patients, which is very exciting because previously treated patients really have very few treatment options,” Jennifer Brudno, MD, with the National Cancer Institute and coauthor of the JAMA review, said in a journal podcast.
Several cell-based agents are in early trials to treat a range of solid tumors.
Hinrichs and colleagues previously reported findings from a phase 2 clinical trial of TIL therapy for human papillomavirus (HPV) — associated cancers including cervical, oropharyngeal, and anal cancers. Responses occurred in 5 of 18 patients with cervical cancer and 2 of 11 patients with noncervical cancers. “Two of the patients with cervical cancer had complete responses that are ongoing years after a single infusion of cells,” Hinrichs told this news organization.
Hinrichs was also involved in a phase 1 trial of gene-engineered TCR T-cells targeting HPV E7 for HPV-associated cancers reported tumor responses in 6 of 12 patients, including 4 of 8 with tumors refractory to checkpoint blockade immunotherapy. A phase 2 trial is now open at Rutgers Cancer Institute, as is an early trial testing a new TCR T-cell therapy targeting Kita-Kyushu Lung Cancer Antigen-1 to treat metastatic gastric, lung, breast, and cervical cancers.
Despite the encouraging findings, for CAR T-cell and other cell-based therapies to be successful against solid tumors, “we need to develop more treatments directed against antigens that are expressed by most or all the cells in a tumor but not by critical healthy tissues,” Hinrichs said.
“It may also be important to increase the potency of therapeutic cells and develop more sophisticated methods of antigen targeting that can better distinguish between tumors and healthy tissues,” he noted.
Brudno reported being an unpaid scientific advisory board member for and receiving travel expenses from Kyverna Therapeutics. Hinrichs reported receiving personal fees from Neogene Therapeutics, Capstan Therapeutics, GlaxoSmithKline, Vir Biotechnology, and PACT Pharma; equity from Scarlet TCR (company officer); and sponsored research agreements from T-Cure Biosciences and Neogene Therapeutics outside the submitted work. He also holds several patents related to cellular therapies.
A version of this article first appeared on Medscape.com.
Chimeric antigen receptor (CAR) T-cell therapy has shown efficacy in blood cancers — with six CAR T-cell products now approved by the Food and Drug Administration (FDA) to treat six hematologic malignancies.
For solid tumors, however, the efficacy of CAR T-cell treatments has been limited and progress “more incremental,” Christian Hinrichs, MD, with Rutgers Cancer Institute in New Brunswick, New Jersey, told this news organization. Currently, there are no CAR T-cell therapies approved in the United States to treat solid tumors.
Why have CAR T-cell therapies been less effective against solid tumors?
Perhaps the biggest hurdle is the ability to identify and selectively target specific molecular structures in cancer cells without causing severe toxicity by injuring healthy cells, Hinrichs and coauthors wrote in a recent JAMA review.
CAR T-cells are made up of “T cells genetically engineered to express a synthetic receptor that recognizes a tumor cell-surface protein,” Hinrichs and colleagues explained. But identifying cell surface antigens that are exclusive to solid tumor cells has been a challenge, which means CAR T-cell therapies end up affecting both tumor and healthy tissues.
“This makes it difficult to target and kill all the tumor cells without causing severe toxicity from injury to healthy cells,” Hinrichs explained.
Other common obstacles include challenges penetrating the dense extracellular matrix of solid tumors and the need to overcome inhibitory cells and molecules in the tumor microenvironment.
Despite the challenges and slow progress, some “promising results” have begun to emerge in the solid tumor, CAR T-cell space, Hinrichs said.
A recent phase 1-2 study, for instance, found that 63% (17 of 27) of pediatric patients with heavily pretreated neuroblastoma achieved an overall response with an investigational CAR T-cell therapy, GD2-CART01.
In a recent phase 1 trial, 38 of 98 patients with gastrointestinal cancers (39%) achieved partial or complete responses after receiving an investigational CAR T-cell treatment directed at Claudin18.2. However, the responses were short overall and could have been related to the chemotherapy given before the CAR T-cell infusion.
Another phase 1 trial found that a GPC3-targeted CAR T-cell therapy led to an objective response rate in half (12 of 24) of heavily treated patients with advanced hepatocellular carcinoma, with a disease control rate of almost 91%.
Outside of CAR-T cell therapies, other cell-based treatments have shown promise against solid tumors, including two T-cell therapies recently approved by the FDA.
Last February, the FDA approved the tumor-infiltrating lymphocyte (TIL) therapy lifileucel (Amtagvi) for advanced melanoma. In August, the agency approved the T-cell receptor (TCR) therapy afamitresgene autoleucel for advanced synovial sarcoma.
“Response rates for these cellular therapies are in the 30% range, but already there is clear data that there’s durability for some patients, which is very exciting because previously treated patients really have very few treatment options,” Jennifer Brudno, MD, with the National Cancer Institute and coauthor of the JAMA review, said in a journal podcast.
Several cell-based agents are in early trials to treat a range of solid tumors.
Hinrichs and colleagues previously reported findings from a phase 2 clinical trial of TIL therapy for human papillomavirus (HPV) — associated cancers including cervical, oropharyngeal, and anal cancers. Responses occurred in 5 of 18 patients with cervical cancer and 2 of 11 patients with noncervical cancers. “Two of the patients with cervical cancer had complete responses that are ongoing years after a single infusion of cells,” Hinrichs told this news organization.
Hinrichs was also involved in a phase 1 trial of gene-engineered TCR T-cells targeting HPV E7 for HPV-associated cancers reported tumor responses in 6 of 12 patients, including 4 of 8 with tumors refractory to checkpoint blockade immunotherapy. A phase 2 trial is now open at Rutgers Cancer Institute, as is an early trial testing a new TCR T-cell therapy targeting Kita-Kyushu Lung Cancer Antigen-1 to treat metastatic gastric, lung, breast, and cervical cancers.
Despite the encouraging findings, for CAR T-cell and other cell-based therapies to be successful against solid tumors, “we need to develop more treatments directed against antigens that are expressed by most or all the cells in a tumor but not by critical healthy tissues,” Hinrichs said.
“It may also be important to increase the potency of therapeutic cells and develop more sophisticated methods of antigen targeting that can better distinguish between tumors and healthy tissues,” he noted.
Brudno reported being an unpaid scientific advisory board member for and receiving travel expenses from Kyverna Therapeutics. Hinrichs reported receiving personal fees from Neogene Therapeutics, Capstan Therapeutics, GlaxoSmithKline, Vir Biotechnology, and PACT Pharma; equity from Scarlet TCR (company officer); and sponsored research agreements from T-Cure Biosciences and Neogene Therapeutics outside the submitted work. He also holds several patents related to cellular therapies.
A version of this article first appeared on Medscape.com.
Chimeric antigen receptor (CAR) T-cell therapy has shown efficacy in blood cancers — with six CAR T-cell products now approved by the Food and Drug Administration (FDA) to treat six hematologic malignancies.
For solid tumors, however, the efficacy of CAR T-cell treatments has been limited and progress “more incremental,” Christian Hinrichs, MD, with Rutgers Cancer Institute in New Brunswick, New Jersey, told this news organization. Currently, there are no CAR T-cell therapies approved in the United States to treat solid tumors.
Why have CAR T-cell therapies been less effective against solid tumors?
Perhaps the biggest hurdle is the ability to identify and selectively target specific molecular structures in cancer cells without causing severe toxicity by injuring healthy cells, Hinrichs and coauthors wrote in a recent JAMA review.
CAR T-cells are made up of “T cells genetically engineered to express a synthetic receptor that recognizes a tumor cell-surface protein,” Hinrichs and colleagues explained. But identifying cell surface antigens that are exclusive to solid tumor cells has been a challenge, which means CAR T-cell therapies end up affecting both tumor and healthy tissues.
“This makes it difficult to target and kill all the tumor cells without causing severe toxicity from injury to healthy cells,” Hinrichs explained.
Other common obstacles include challenges penetrating the dense extracellular matrix of solid tumors and the need to overcome inhibitory cells and molecules in the tumor microenvironment.
Despite the challenges and slow progress, some “promising results” have begun to emerge in the solid tumor, CAR T-cell space, Hinrichs said.
A recent phase 1-2 study, for instance, found that 63% (17 of 27) of pediatric patients with heavily pretreated neuroblastoma achieved an overall response with an investigational CAR T-cell therapy, GD2-CART01.
In a recent phase 1 trial, 38 of 98 patients with gastrointestinal cancers (39%) achieved partial or complete responses after receiving an investigational CAR T-cell treatment directed at Claudin18.2. However, the responses were short overall and could have been related to the chemotherapy given before the CAR T-cell infusion.
Another phase 1 trial found that a GPC3-targeted CAR T-cell therapy led to an objective response rate in half (12 of 24) of heavily treated patients with advanced hepatocellular carcinoma, with a disease control rate of almost 91%.
Outside of CAR-T cell therapies, other cell-based treatments have shown promise against solid tumors, including two T-cell therapies recently approved by the FDA.
Last February, the FDA approved the tumor-infiltrating lymphocyte (TIL) therapy lifileucel (Amtagvi) for advanced melanoma. In August, the agency approved the T-cell receptor (TCR) therapy afamitresgene autoleucel for advanced synovial sarcoma.
“Response rates for these cellular therapies are in the 30% range, but already there is clear data that there’s durability for some patients, which is very exciting because previously treated patients really have very few treatment options,” Jennifer Brudno, MD, with the National Cancer Institute and coauthor of the JAMA review, said in a journal podcast.
Several cell-based agents are in early trials to treat a range of solid tumors.
Hinrichs and colleagues previously reported findings from a phase 2 clinical trial of TIL therapy for human papillomavirus (HPV) — associated cancers including cervical, oropharyngeal, and anal cancers. Responses occurred in 5 of 18 patients with cervical cancer and 2 of 11 patients with noncervical cancers. “Two of the patients with cervical cancer had complete responses that are ongoing years after a single infusion of cells,” Hinrichs told this news organization.
Hinrichs was also involved in a phase 1 trial of gene-engineered TCR T-cells targeting HPV E7 for HPV-associated cancers reported tumor responses in 6 of 12 patients, including 4 of 8 with tumors refractory to checkpoint blockade immunotherapy. A phase 2 trial is now open at Rutgers Cancer Institute, as is an early trial testing a new TCR T-cell therapy targeting Kita-Kyushu Lung Cancer Antigen-1 to treat metastatic gastric, lung, breast, and cervical cancers.
Despite the encouraging findings, for CAR T-cell and other cell-based therapies to be successful against solid tumors, “we need to develop more treatments directed against antigens that are expressed by most or all the cells in a tumor but not by critical healthy tissues,” Hinrichs said.
“It may also be important to increase the potency of therapeutic cells and develop more sophisticated methods of antigen targeting that can better distinguish between tumors and healthy tissues,” he noted.
Brudno reported being an unpaid scientific advisory board member for and receiving travel expenses from Kyverna Therapeutics. Hinrichs reported receiving personal fees from Neogene Therapeutics, Capstan Therapeutics, GlaxoSmithKline, Vir Biotechnology, and PACT Pharma; equity from Scarlet TCR (company officer); and sponsored research agreements from T-Cure Biosciences and Neogene Therapeutics outside the submitted work. He also holds several patents related to cellular therapies.
A version of this article first appeared on Medscape.com.
Promising New Blood Test for Colorectal Cancer Screening
, the largest study of any blood-based CRC screening test.
With continued optimization, this blood test “may provide a convenient, effective option for colorectal cancer screening in the intended use population,” said Aasma Shaukat, MD, MPH, AGAF, with New York University Grossman School of Medicine in New York City.
CRC screening rates remain suboptimal, with nearly 40% of eligible adults in the United States not up to date with screening, noted Shaukat, who presented the study results at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium 2025 in San Francisco.
Blood-based testing offers a promising complementary approach that may boost patient adherence among unscreened individuals, she added.
The study evaluated the clinical performance of the investigational blood-based screening test in 27,010 adults aged ≥ 45 years at average-risk for CRC. Patients with no personal history of cancer, colorectal adenoma, or inflammatory bowel disease, as well as no family history of CRC or hereditary gastrointestinal cancer syndromes were eligible for the study.
Participants had blood drawn before bowel preparation for colonoscopy, and the blood test results were measured against colonoscopy findings.
The primary endpoints included sensitivity for CRC, specificity for advanced colorectal neoplasia, and negative and positive predictive value for advanced colorectal neoplasia. A secondary endpoint was sensitivity for advanced precancerous lesions.
The blood-based screening test met all primary endpoints, with a sensitivity for CRC of 79.2% and a specificity for advanced colorectal neoplasia of 91.5%, Shaukat reported at a conference briefing. Negative predictive value for advanced colorectal neoplasia was 90.8%, though the positive predictive value was only 15.5% and sensitivity for advanced precancerous lesions, a secondary endpoint, was 12.5%.
Similar results were achieved in a prespecified analysis in which performance of the blood test was weighted to match US census data for sex and age distributions. Sensitivity for CRC was 81.1%, specificity was 90.4%, and negative predictive value for advanced colorectal neoplasia was 90.5%; but the positive predictive value was 15.5%, and the sensitivity for advanced precancerous lesions was 13.7%.
This type of analysis provides “a snapshot of how [the test] would perform in the US population,” Shaukat explained, adding that the sensitivity for CRC and advanced precursor lesions was “lower than expected and will continue to be optimized in future research and development.”
It will also be important to determine when the test should be repeated and how often and to look at the determinants around cost and comparative effectiveness, she said. Modeling and other outcome studies — which will be forthcoming in the future years — could help shed some light on these questions.
Briefing moderator Julie Gralow, MD, ASCO chief medical officer, said it will be important to compare how this new blood test compares with Guardant Health’s Shield CRC blood test that was approved in 2024. Although there’s no study directly comparing the new blood test to Shield, data from the ECLIPSE study reported that Shield had 83% sensitivity for CRC and 90% specificity for advanced neoplasia, but only 13% sensitivity for advanced precancerous lesions — which appears similar, so far, to findings reported for the new blood test.
But any screening is better than no screening, and with further study, this blood test may “add another tool to our toolkit,” said Pamela Kunz, MD, director of the Center for Gastrointestinal Cancers at Smilow Cancer Hospital and Yale Cancer Center, New Haven, Connecticut, who spoke at the briefing. Kunz said she is eager to see some of the future work optimizing the sensitivity and subsequent analyses that look at differences by race and ethnicity.
The study had no specific funding. Shaukat consults for Freenome Holdings and Iterative Health. Kunz declared ties with Ipsen, Novartis, Genentech/Roche, Amgen, Crinetics Pharmaceuticals, Natera, HUTCHMED, and ITM Isotope Technologies Munich. Gralow declared consulting or advisory roles with Genentech/Roche.
A version of this article appeared on Medscape.com .
, the largest study of any blood-based CRC screening test.
With continued optimization, this blood test “may provide a convenient, effective option for colorectal cancer screening in the intended use population,” said Aasma Shaukat, MD, MPH, AGAF, with New York University Grossman School of Medicine in New York City.
CRC screening rates remain suboptimal, with nearly 40% of eligible adults in the United States not up to date with screening, noted Shaukat, who presented the study results at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium 2025 in San Francisco.
Blood-based testing offers a promising complementary approach that may boost patient adherence among unscreened individuals, she added.
The study evaluated the clinical performance of the investigational blood-based screening test in 27,010 adults aged ≥ 45 years at average-risk for CRC. Patients with no personal history of cancer, colorectal adenoma, or inflammatory bowel disease, as well as no family history of CRC or hereditary gastrointestinal cancer syndromes were eligible for the study.
Participants had blood drawn before bowel preparation for colonoscopy, and the blood test results were measured against colonoscopy findings.
The primary endpoints included sensitivity for CRC, specificity for advanced colorectal neoplasia, and negative and positive predictive value for advanced colorectal neoplasia. A secondary endpoint was sensitivity for advanced precancerous lesions.
The blood-based screening test met all primary endpoints, with a sensitivity for CRC of 79.2% and a specificity for advanced colorectal neoplasia of 91.5%, Shaukat reported at a conference briefing. Negative predictive value for advanced colorectal neoplasia was 90.8%, though the positive predictive value was only 15.5% and sensitivity for advanced precancerous lesions, a secondary endpoint, was 12.5%.
Similar results were achieved in a prespecified analysis in which performance of the blood test was weighted to match US census data for sex and age distributions. Sensitivity for CRC was 81.1%, specificity was 90.4%, and negative predictive value for advanced colorectal neoplasia was 90.5%; but the positive predictive value was 15.5%, and the sensitivity for advanced precancerous lesions was 13.7%.
This type of analysis provides “a snapshot of how [the test] would perform in the US population,” Shaukat explained, adding that the sensitivity for CRC and advanced precursor lesions was “lower than expected and will continue to be optimized in future research and development.”
It will also be important to determine when the test should be repeated and how often and to look at the determinants around cost and comparative effectiveness, she said. Modeling and other outcome studies — which will be forthcoming in the future years — could help shed some light on these questions.
Briefing moderator Julie Gralow, MD, ASCO chief medical officer, said it will be important to compare how this new blood test compares with Guardant Health’s Shield CRC blood test that was approved in 2024. Although there’s no study directly comparing the new blood test to Shield, data from the ECLIPSE study reported that Shield had 83% sensitivity for CRC and 90% specificity for advanced neoplasia, but only 13% sensitivity for advanced precancerous lesions — which appears similar, so far, to findings reported for the new blood test.
But any screening is better than no screening, and with further study, this blood test may “add another tool to our toolkit,” said Pamela Kunz, MD, director of the Center for Gastrointestinal Cancers at Smilow Cancer Hospital and Yale Cancer Center, New Haven, Connecticut, who spoke at the briefing. Kunz said she is eager to see some of the future work optimizing the sensitivity and subsequent analyses that look at differences by race and ethnicity.
The study had no specific funding. Shaukat consults for Freenome Holdings and Iterative Health. Kunz declared ties with Ipsen, Novartis, Genentech/Roche, Amgen, Crinetics Pharmaceuticals, Natera, HUTCHMED, and ITM Isotope Technologies Munich. Gralow declared consulting or advisory roles with Genentech/Roche.
A version of this article appeared on Medscape.com .
, the largest study of any blood-based CRC screening test.
With continued optimization, this blood test “may provide a convenient, effective option for colorectal cancer screening in the intended use population,” said Aasma Shaukat, MD, MPH, AGAF, with New York University Grossman School of Medicine in New York City.
CRC screening rates remain suboptimal, with nearly 40% of eligible adults in the United States not up to date with screening, noted Shaukat, who presented the study results at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium 2025 in San Francisco.
Blood-based testing offers a promising complementary approach that may boost patient adherence among unscreened individuals, she added.
The study evaluated the clinical performance of the investigational blood-based screening test in 27,010 adults aged ≥ 45 years at average-risk for CRC. Patients with no personal history of cancer, colorectal adenoma, or inflammatory bowel disease, as well as no family history of CRC or hereditary gastrointestinal cancer syndromes were eligible for the study.
Participants had blood drawn before bowel preparation for colonoscopy, and the blood test results were measured against colonoscopy findings.
The primary endpoints included sensitivity for CRC, specificity for advanced colorectal neoplasia, and negative and positive predictive value for advanced colorectal neoplasia. A secondary endpoint was sensitivity for advanced precancerous lesions.
The blood-based screening test met all primary endpoints, with a sensitivity for CRC of 79.2% and a specificity for advanced colorectal neoplasia of 91.5%, Shaukat reported at a conference briefing. Negative predictive value for advanced colorectal neoplasia was 90.8%, though the positive predictive value was only 15.5% and sensitivity for advanced precancerous lesions, a secondary endpoint, was 12.5%.
Similar results were achieved in a prespecified analysis in which performance of the blood test was weighted to match US census data for sex and age distributions. Sensitivity for CRC was 81.1%, specificity was 90.4%, and negative predictive value for advanced colorectal neoplasia was 90.5%; but the positive predictive value was 15.5%, and the sensitivity for advanced precancerous lesions was 13.7%.
This type of analysis provides “a snapshot of how [the test] would perform in the US population,” Shaukat explained, adding that the sensitivity for CRC and advanced precursor lesions was “lower than expected and will continue to be optimized in future research and development.”
It will also be important to determine when the test should be repeated and how often and to look at the determinants around cost and comparative effectiveness, she said. Modeling and other outcome studies — which will be forthcoming in the future years — could help shed some light on these questions.
Briefing moderator Julie Gralow, MD, ASCO chief medical officer, said it will be important to compare how this new blood test compares with Guardant Health’s Shield CRC blood test that was approved in 2024. Although there’s no study directly comparing the new blood test to Shield, data from the ECLIPSE study reported that Shield had 83% sensitivity for CRC and 90% specificity for advanced neoplasia, but only 13% sensitivity for advanced precancerous lesions — which appears similar, so far, to findings reported for the new blood test.
But any screening is better than no screening, and with further study, this blood test may “add another tool to our toolkit,” said Pamela Kunz, MD, director of the Center for Gastrointestinal Cancers at Smilow Cancer Hospital and Yale Cancer Center, New Haven, Connecticut, who spoke at the briefing. Kunz said she is eager to see some of the future work optimizing the sensitivity and subsequent analyses that look at differences by race and ethnicity.
The study had no specific funding. Shaukat consults for Freenome Holdings and Iterative Health. Kunz declared ties with Ipsen, Novartis, Genentech/Roche, Amgen, Crinetics Pharmaceuticals, Natera, HUTCHMED, and ITM Isotope Technologies Munich. Gralow declared consulting or advisory roles with Genentech/Roche.
A version of this article appeared on Medscape.com .
FROM ASCO GI 2025
Low-Dose Aspirin Cuts CRC Recurrence
according to findings from the phase 3 ALASCCA trial.
These results stress “the importance of upfront genomic testing” in patients with CRC, said Anna Martling, MD, PhD, from Karolinska Institutet, Stockholm, Sweden, who reported the findings at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium 2025 in San Francisco.
This is the first trial to show that mutations in the PI3K signaling pathway, beyond PIK3CA alterations, predict aspirin response, “expanding the targetable patient population substantially,” Martling added. Genetic mutations along the PI3K signaling pathway are found in about 30% of CRCs.
While aspirin as chemoprevention in CRC has been studied, data confirming its effectiveness as well as uptake of this approach in practice have been lacking, explained ASCO expert commenter Pamela Kunz, MD, with Smilow Cancer Hospital and Yale Cancer Center, New Haven, Connecticut.
“It’s really clear that this is a practice-changing study,” said Kunz. The findings indicate that this approach “checks all of the boxes: It’s effective, it’s low risk, it’s inexpensive, and it’s easy to administer.”
The trial included 626 patients (median age, 66 years; 52% women) with stages II-III colon cancer (67%) or stages I-III rectal cancer (33%) across 33 hospitals in Sweden, Denmark, Finland, and Norway.
Patients were stratified into two groups based on specific PI3K pathway alterations Group A (n = 314) included patients with PIK3CA mutations in exon 9 and/or 20, and group B (n = 312) included those with other PI3K pathway mutations, including PIK3CA mutations outside exon 9/20, or mutations in PIK3R1 or PTEN genes.
Participants in both groups were randomly allocated 1:1 to 160 mg/d of aspirin or placebo for 3 years. The primary outcome was CRC recurrence; disease-free survival was a secondary outcome.
Compared with placebo, aspirin reduced the risk for recurrence by 51% (hazard ratio [HR], 0.49) in patients with PIK3CA mutations, with a 3-year recurrence rate of 7.7% in those taking aspirin vs 14.1% in the placebo group.
“Interestingly,” Martling noted, in the exploratory arm that included other mutations along the PIK3 pathway beyond PIK3CA (Group B), the effect was even stronger. Patients in this group had a 58% (HR, 0.42) lower risk for recurrence than those in the placebo group, with a 3-year recurrence rate of 7.7% in the aspirin group vs 16.8% recurrence rate in the placebo group.
Aspirin also had a disease-free survival benefit in both groups, but it was significant only in group B.
While the study was not specifically designed for subgroup analysis, the benefit of aspirin was observed in all subgroups examined, including men and women with colon or rectal cancer, those who did and did not receive neoadjuvant or adjuvant treatment, and those with stages I-III disease.
The incidence of adverse events was as expected and severe side effects associated with 160 mg/d aspirin were rare, Martling said.
Both Martling and Kunz predicted that these findings will change clinical practice. “I anticipate that we’ll be seeing adoption of this [strategy],” Kunz said.
This study received funding from the Swedish Research Council, Swedish Cancer Society, ALF (a regional agreement on medical training and clinical research between the Stockholm County Council and Karolinska Institutet), and the Stockholm Cancer Society. Martling disclosed various relationships with Bactiguard, Smartcella, CarpoNovum and Pfizer. Kunz disclosed relationships with Bristol-Myers Squibb, Novartis and TayzeBio.
A version of this article appeared on Medscape.com .
according to findings from the phase 3 ALASCCA trial.
These results stress “the importance of upfront genomic testing” in patients with CRC, said Anna Martling, MD, PhD, from Karolinska Institutet, Stockholm, Sweden, who reported the findings at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium 2025 in San Francisco.
This is the first trial to show that mutations in the PI3K signaling pathway, beyond PIK3CA alterations, predict aspirin response, “expanding the targetable patient population substantially,” Martling added. Genetic mutations along the PI3K signaling pathway are found in about 30% of CRCs.
While aspirin as chemoprevention in CRC has been studied, data confirming its effectiveness as well as uptake of this approach in practice have been lacking, explained ASCO expert commenter Pamela Kunz, MD, with Smilow Cancer Hospital and Yale Cancer Center, New Haven, Connecticut.
“It’s really clear that this is a practice-changing study,” said Kunz. The findings indicate that this approach “checks all of the boxes: It’s effective, it’s low risk, it’s inexpensive, and it’s easy to administer.”
The trial included 626 patients (median age, 66 years; 52% women) with stages II-III colon cancer (67%) or stages I-III rectal cancer (33%) across 33 hospitals in Sweden, Denmark, Finland, and Norway.
Patients were stratified into two groups based on specific PI3K pathway alterations Group A (n = 314) included patients with PIK3CA mutations in exon 9 and/or 20, and group B (n = 312) included those with other PI3K pathway mutations, including PIK3CA mutations outside exon 9/20, or mutations in PIK3R1 or PTEN genes.
Participants in both groups were randomly allocated 1:1 to 160 mg/d of aspirin or placebo for 3 years. The primary outcome was CRC recurrence; disease-free survival was a secondary outcome.
Compared with placebo, aspirin reduced the risk for recurrence by 51% (hazard ratio [HR], 0.49) in patients with PIK3CA mutations, with a 3-year recurrence rate of 7.7% in those taking aspirin vs 14.1% in the placebo group.
“Interestingly,” Martling noted, in the exploratory arm that included other mutations along the PIK3 pathway beyond PIK3CA (Group B), the effect was even stronger. Patients in this group had a 58% (HR, 0.42) lower risk for recurrence than those in the placebo group, with a 3-year recurrence rate of 7.7% in the aspirin group vs 16.8% recurrence rate in the placebo group.
Aspirin also had a disease-free survival benefit in both groups, but it was significant only in group B.
While the study was not specifically designed for subgroup analysis, the benefit of aspirin was observed in all subgroups examined, including men and women with colon or rectal cancer, those who did and did not receive neoadjuvant or adjuvant treatment, and those with stages I-III disease.
The incidence of adverse events was as expected and severe side effects associated with 160 mg/d aspirin were rare, Martling said.
Both Martling and Kunz predicted that these findings will change clinical practice. “I anticipate that we’ll be seeing adoption of this [strategy],” Kunz said.
This study received funding from the Swedish Research Council, Swedish Cancer Society, ALF (a regional agreement on medical training and clinical research between the Stockholm County Council and Karolinska Institutet), and the Stockholm Cancer Society. Martling disclosed various relationships with Bactiguard, Smartcella, CarpoNovum and Pfizer. Kunz disclosed relationships with Bristol-Myers Squibb, Novartis and TayzeBio.
A version of this article appeared on Medscape.com .
according to findings from the phase 3 ALASCCA trial.
These results stress “the importance of upfront genomic testing” in patients with CRC, said Anna Martling, MD, PhD, from Karolinska Institutet, Stockholm, Sweden, who reported the findings at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium 2025 in San Francisco.
This is the first trial to show that mutations in the PI3K signaling pathway, beyond PIK3CA alterations, predict aspirin response, “expanding the targetable patient population substantially,” Martling added. Genetic mutations along the PI3K signaling pathway are found in about 30% of CRCs.
While aspirin as chemoprevention in CRC has been studied, data confirming its effectiveness as well as uptake of this approach in practice have been lacking, explained ASCO expert commenter Pamela Kunz, MD, with Smilow Cancer Hospital and Yale Cancer Center, New Haven, Connecticut.
“It’s really clear that this is a practice-changing study,” said Kunz. The findings indicate that this approach “checks all of the boxes: It’s effective, it’s low risk, it’s inexpensive, and it’s easy to administer.”
The trial included 626 patients (median age, 66 years; 52% women) with stages II-III colon cancer (67%) or stages I-III rectal cancer (33%) across 33 hospitals in Sweden, Denmark, Finland, and Norway.
Patients were stratified into two groups based on specific PI3K pathway alterations Group A (n = 314) included patients with PIK3CA mutations in exon 9 and/or 20, and group B (n = 312) included those with other PI3K pathway mutations, including PIK3CA mutations outside exon 9/20, or mutations in PIK3R1 or PTEN genes.
Participants in both groups were randomly allocated 1:1 to 160 mg/d of aspirin or placebo for 3 years. The primary outcome was CRC recurrence; disease-free survival was a secondary outcome.
Compared with placebo, aspirin reduced the risk for recurrence by 51% (hazard ratio [HR], 0.49) in patients with PIK3CA mutations, with a 3-year recurrence rate of 7.7% in those taking aspirin vs 14.1% in the placebo group.
“Interestingly,” Martling noted, in the exploratory arm that included other mutations along the PIK3 pathway beyond PIK3CA (Group B), the effect was even stronger. Patients in this group had a 58% (HR, 0.42) lower risk for recurrence than those in the placebo group, with a 3-year recurrence rate of 7.7% in the aspirin group vs 16.8% recurrence rate in the placebo group.
Aspirin also had a disease-free survival benefit in both groups, but it was significant only in group B.
While the study was not specifically designed for subgroup analysis, the benefit of aspirin was observed in all subgroups examined, including men and women with colon or rectal cancer, those who did and did not receive neoadjuvant or adjuvant treatment, and those with stages I-III disease.
The incidence of adverse events was as expected and severe side effects associated with 160 mg/d aspirin were rare, Martling said.
Both Martling and Kunz predicted that these findings will change clinical practice. “I anticipate that we’ll be seeing adoption of this [strategy],” Kunz said.
This study received funding from the Swedish Research Council, Swedish Cancer Society, ALF (a regional agreement on medical training and clinical research between the Stockholm County Council and Karolinska Institutet), and the Stockholm Cancer Society. Martling disclosed various relationships with Bactiguard, Smartcella, CarpoNovum and Pfizer. Kunz disclosed relationships with Bristol-Myers Squibb, Novartis and TayzeBio.
A version of this article appeared on Medscape.com .
FROM ASCO GI 2025
VA Study Asks: Has Active Surveillance Solved the Problem of Overtreatment?
Overtreatment of men with prostate cancer and limited life expectancy (LE) has persisted in the era of active surveillance and worsened in some instances, according to a new study of nearly 250,000 veterans.
“Overtreatment of men with limited longevity for intermediate- and high-risk tumors has not only failed to improve but has actually worsened over the last 20 years,” Timothy Daskivich, MD, MSHPM, with Cedars-Sinai Medical Center, Los Angeles, said in an interview.
“Many doctors assume that the increase in uptake of active surveillance for low-risk prostate cancers has solved the problem of overtreatment, but this trend has not affected overtreatment of men with low likelihood of living long enough to benefit from treatment who have higher-risk tumors,” Daskivich said.
The study was published online on November 11 in JAMA Internal Medicine.
‘Concerning’ Real-World Data
For men with low- and intermediate-risk prostate cancer expected to live fewer than 10 years, prostate cancer screening and aggressive treatment are not recommended.
Daskivich and colleagues analyzed data on 243,928 men (mean age, 66 years) in the Veterans Affairs (VA) Health System with clinically localized prostate cancer diagnosed between 2000 and 2019.
About 21% had LE < 10 years, and about 4% had LE < 5 years, according to the validated age-adjusted Prostate Cancer Comorbidity Index.
Overtreatment was defined as aggressive treatment (surgery or radiation) in those with LE < 10 years and low- to intermediate-risk disease and in those with LE < 5 years and high-risk disease, in line with current guidelines.
Among men with LE < 10 years, the proportion of men overtreated with surgery or radiotherapy for low-risk disease decreased 22% but increased 22% for intermediate-risk disease during the study period.
Among men with LE < 5 years, the proportion of men treated with definitive treatment for high-risk disease increased 29%.
“While lower-risk tumors are treated less aggressively across the board, including in men with limited longevity, it seems that we are more indiscriminately treating men with higher-risk disease without considering their expected longevity,” Daskivich said, in an interview.
Is This Happening in the General US Population?
Daskivich noted that the sample included a large sample of men diagnosed with localized prostate cancer in the VA Health System.
“Rates of overtreatment are likely to be lower in the VA [Health System], so the problem may be worse in the community setting. The VA [Health System] has been exemplary in its uptake of active surveillance for low-risk cancers, leading the effort to reduce overtreatment of men with low-risk cancers. However, the problem of overtreatment of men with limited longevity persists in the VA [Health System], underscoring the pervasiveness of this problem,” he explained.
“We don’t have a perfect head-to-head comparison of overtreatment in the VA setting vs in the community. [However, one study shows] that this is not a VA-specific phenomenon and that there is an increase in overtreatment of men with limited longevity in a Medicare population as well,” Daskivich noted.
Is Overtreatment All Bad?
Overtreatment of prostate cancer, especially in cases where the cancer is unlikely to progress or cause symptoms, can lead to significant physical, psychological, and financial harms, Christopher Anderson, MD, urologist with Columbia University Irving Medical Center in New York City, who wasn’t involved in the study, noted in an interview.
In the study by Daskivich and colleagues, over three quarters of the overtreatment was radiation therapy, which carries the risk for urinary, bowel, and sexual issues.
“Overscreening, which can lead to overtreatment, is a core issue,” Anderson said. It’s easy to order a “simple” prostate-specific antigen blood test, but in an older man with limited LE, that can lead to a host of further testing, he commented.
Stopping the pipeline of overscreening that then feeds into the cascade of overtreatment is the first step in addressing the problem of prostate cancer overtreatment, Nancy Li Schoenborn, MD, MHS, with Johns Hopkins University School of Medicine, Baltimore, and Louise C. Walter, MD, with University of California San Francisco, wrote in an editorial in JAMA Internal Medicine.
Considering LE during screening decision-making is “fundamental to reducing harms of prostate cancer overdiagnosis and overtreatment” because limited LE increases the likelihood of experiencing “harms all along the diagnostic and treatment cascade following screening,” the editorial writers said.
The time spent diagnosing, monitoring, and treating asymptomatic prostate cancer in men with limited LE distracts from monitoring and treating chronic symptomatic life-limiting illnesses, they noted.
Tough to Talk About?
Anderson noted that, in general, doctors are not great at estimating and counseling patients on LE. “It’s sometimes difficult to have that conversation,” he said.
Daskivich said physicians may fail to include average LE when advising patients on treatments because they believe that the patients do not want to discuss this topic. “Yet, in interviews with patients, we found that prostate cancer patients reported they wanted this information,” he continued, in an interview.
Solving the problem of overscreening and overtreatment will require a “multifaceted approach, including improving access to life expectancy data at the point of care for providers, educating providers on how to communicate this information, and improving data sources to predict longevity,” Daskivich said.
He said it’s equally important to note that some men with prostate cancer may choose treatment even if they have a limited longevity.
“Not all patients will choose conservative management, even if it is recommended by guidelines. However, they need to be given the opportunity to make a good decision for themselves with the best possible data,” Daskivich said.
This work was supported in part by a US Department of VA Merit Review. Daskivich reported receiving personal fees from the Medical Education Speakers Network, EDAP, and RAND; research support from Lantheus and Janssen; and a patent pending for a system for healthcare visit quality assessment outside the submitted work. Schoenborn, Walter, and Anderson had no relevant disclosures.
A version of this article first appeared on Medscape.com.
Overtreatment of men with prostate cancer and limited life expectancy (LE) has persisted in the era of active surveillance and worsened in some instances, according to a new study of nearly 250,000 veterans.
“Overtreatment of men with limited longevity for intermediate- and high-risk tumors has not only failed to improve but has actually worsened over the last 20 years,” Timothy Daskivich, MD, MSHPM, with Cedars-Sinai Medical Center, Los Angeles, said in an interview.
“Many doctors assume that the increase in uptake of active surveillance for low-risk prostate cancers has solved the problem of overtreatment, but this trend has not affected overtreatment of men with low likelihood of living long enough to benefit from treatment who have higher-risk tumors,” Daskivich said.
The study was published online on November 11 in JAMA Internal Medicine.
‘Concerning’ Real-World Data
For men with low- and intermediate-risk prostate cancer expected to live fewer than 10 years, prostate cancer screening and aggressive treatment are not recommended.
Daskivich and colleagues analyzed data on 243,928 men (mean age, 66 years) in the Veterans Affairs (VA) Health System with clinically localized prostate cancer diagnosed between 2000 and 2019.
About 21% had LE < 10 years, and about 4% had LE < 5 years, according to the validated age-adjusted Prostate Cancer Comorbidity Index.
Overtreatment was defined as aggressive treatment (surgery or radiation) in those with LE < 10 years and low- to intermediate-risk disease and in those with LE < 5 years and high-risk disease, in line with current guidelines.
Among men with LE < 10 years, the proportion of men overtreated with surgery or radiotherapy for low-risk disease decreased 22% but increased 22% for intermediate-risk disease during the study period.
Among men with LE < 5 years, the proportion of men treated with definitive treatment for high-risk disease increased 29%.
“While lower-risk tumors are treated less aggressively across the board, including in men with limited longevity, it seems that we are more indiscriminately treating men with higher-risk disease without considering their expected longevity,” Daskivich said, in an interview.
Is This Happening in the General US Population?
Daskivich noted that the sample included a large sample of men diagnosed with localized prostate cancer in the VA Health System.
“Rates of overtreatment are likely to be lower in the VA [Health System], so the problem may be worse in the community setting. The VA [Health System] has been exemplary in its uptake of active surveillance for low-risk cancers, leading the effort to reduce overtreatment of men with low-risk cancers. However, the problem of overtreatment of men with limited longevity persists in the VA [Health System], underscoring the pervasiveness of this problem,” he explained.
“We don’t have a perfect head-to-head comparison of overtreatment in the VA setting vs in the community. [However, one study shows] that this is not a VA-specific phenomenon and that there is an increase in overtreatment of men with limited longevity in a Medicare population as well,” Daskivich noted.
Is Overtreatment All Bad?
Overtreatment of prostate cancer, especially in cases where the cancer is unlikely to progress or cause symptoms, can lead to significant physical, psychological, and financial harms, Christopher Anderson, MD, urologist with Columbia University Irving Medical Center in New York City, who wasn’t involved in the study, noted in an interview.
In the study by Daskivich and colleagues, over three quarters of the overtreatment was radiation therapy, which carries the risk for urinary, bowel, and sexual issues.
“Overscreening, which can lead to overtreatment, is a core issue,” Anderson said. It’s easy to order a “simple” prostate-specific antigen blood test, but in an older man with limited LE, that can lead to a host of further testing, he commented.
Stopping the pipeline of overscreening that then feeds into the cascade of overtreatment is the first step in addressing the problem of prostate cancer overtreatment, Nancy Li Schoenborn, MD, MHS, with Johns Hopkins University School of Medicine, Baltimore, and Louise C. Walter, MD, with University of California San Francisco, wrote in an editorial in JAMA Internal Medicine.
Considering LE during screening decision-making is “fundamental to reducing harms of prostate cancer overdiagnosis and overtreatment” because limited LE increases the likelihood of experiencing “harms all along the diagnostic and treatment cascade following screening,” the editorial writers said.
The time spent diagnosing, monitoring, and treating asymptomatic prostate cancer in men with limited LE distracts from monitoring and treating chronic symptomatic life-limiting illnesses, they noted.
Tough to Talk About?
Anderson noted that, in general, doctors are not great at estimating and counseling patients on LE. “It’s sometimes difficult to have that conversation,” he said.
Daskivich said physicians may fail to include average LE when advising patients on treatments because they believe that the patients do not want to discuss this topic. “Yet, in interviews with patients, we found that prostate cancer patients reported they wanted this information,” he continued, in an interview.
Solving the problem of overscreening and overtreatment will require a “multifaceted approach, including improving access to life expectancy data at the point of care for providers, educating providers on how to communicate this information, and improving data sources to predict longevity,” Daskivich said.
He said it’s equally important to note that some men with prostate cancer may choose treatment even if they have a limited longevity.
“Not all patients will choose conservative management, even if it is recommended by guidelines. However, they need to be given the opportunity to make a good decision for themselves with the best possible data,” Daskivich said.
This work was supported in part by a US Department of VA Merit Review. Daskivich reported receiving personal fees from the Medical Education Speakers Network, EDAP, and RAND; research support from Lantheus and Janssen; and a patent pending for a system for healthcare visit quality assessment outside the submitted work. Schoenborn, Walter, and Anderson had no relevant disclosures.
A version of this article first appeared on Medscape.com.
Overtreatment of men with prostate cancer and limited life expectancy (LE) has persisted in the era of active surveillance and worsened in some instances, according to a new study of nearly 250,000 veterans.
“Overtreatment of men with limited longevity for intermediate- and high-risk tumors has not only failed to improve but has actually worsened over the last 20 years,” Timothy Daskivich, MD, MSHPM, with Cedars-Sinai Medical Center, Los Angeles, said in an interview.
“Many doctors assume that the increase in uptake of active surveillance for low-risk prostate cancers has solved the problem of overtreatment, but this trend has not affected overtreatment of men with low likelihood of living long enough to benefit from treatment who have higher-risk tumors,” Daskivich said.
The study was published online on November 11 in JAMA Internal Medicine.
‘Concerning’ Real-World Data
For men with low- and intermediate-risk prostate cancer expected to live fewer than 10 years, prostate cancer screening and aggressive treatment are not recommended.
Daskivich and colleagues analyzed data on 243,928 men (mean age, 66 years) in the Veterans Affairs (VA) Health System with clinically localized prostate cancer diagnosed between 2000 and 2019.
About 21% had LE < 10 years, and about 4% had LE < 5 years, according to the validated age-adjusted Prostate Cancer Comorbidity Index.
Overtreatment was defined as aggressive treatment (surgery or radiation) in those with LE < 10 years and low- to intermediate-risk disease and in those with LE < 5 years and high-risk disease, in line with current guidelines.
Among men with LE < 10 years, the proportion of men overtreated with surgery or radiotherapy for low-risk disease decreased 22% but increased 22% for intermediate-risk disease during the study period.
Among men with LE < 5 years, the proportion of men treated with definitive treatment for high-risk disease increased 29%.
“While lower-risk tumors are treated less aggressively across the board, including in men with limited longevity, it seems that we are more indiscriminately treating men with higher-risk disease without considering their expected longevity,” Daskivich said, in an interview.
Is This Happening in the General US Population?
Daskivich noted that the sample included a large sample of men diagnosed with localized prostate cancer in the VA Health System.
“Rates of overtreatment are likely to be lower in the VA [Health System], so the problem may be worse in the community setting. The VA [Health System] has been exemplary in its uptake of active surveillance for low-risk cancers, leading the effort to reduce overtreatment of men with low-risk cancers. However, the problem of overtreatment of men with limited longevity persists in the VA [Health System], underscoring the pervasiveness of this problem,” he explained.
“We don’t have a perfect head-to-head comparison of overtreatment in the VA setting vs in the community. [However, one study shows] that this is not a VA-specific phenomenon and that there is an increase in overtreatment of men with limited longevity in a Medicare population as well,” Daskivich noted.
Is Overtreatment All Bad?
Overtreatment of prostate cancer, especially in cases where the cancer is unlikely to progress or cause symptoms, can lead to significant physical, psychological, and financial harms, Christopher Anderson, MD, urologist with Columbia University Irving Medical Center in New York City, who wasn’t involved in the study, noted in an interview.
In the study by Daskivich and colleagues, over three quarters of the overtreatment was radiation therapy, which carries the risk for urinary, bowel, and sexual issues.
“Overscreening, which can lead to overtreatment, is a core issue,” Anderson said. It’s easy to order a “simple” prostate-specific antigen blood test, but in an older man with limited LE, that can lead to a host of further testing, he commented.
Stopping the pipeline of overscreening that then feeds into the cascade of overtreatment is the first step in addressing the problem of prostate cancer overtreatment, Nancy Li Schoenborn, MD, MHS, with Johns Hopkins University School of Medicine, Baltimore, and Louise C. Walter, MD, with University of California San Francisco, wrote in an editorial in JAMA Internal Medicine.
Considering LE during screening decision-making is “fundamental to reducing harms of prostate cancer overdiagnosis and overtreatment” because limited LE increases the likelihood of experiencing “harms all along the diagnostic and treatment cascade following screening,” the editorial writers said.
The time spent diagnosing, monitoring, and treating asymptomatic prostate cancer in men with limited LE distracts from monitoring and treating chronic symptomatic life-limiting illnesses, they noted.
Tough to Talk About?
Anderson noted that, in general, doctors are not great at estimating and counseling patients on LE. “It’s sometimes difficult to have that conversation,” he said.
Daskivich said physicians may fail to include average LE when advising patients on treatments because they believe that the patients do not want to discuss this topic. “Yet, in interviews with patients, we found that prostate cancer patients reported they wanted this information,” he continued, in an interview.
Solving the problem of overscreening and overtreatment will require a “multifaceted approach, including improving access to life expectancy data at the point of care for providers, educating providers on how to communicate this information, and improving data sources to predict longevity,” Daskivich said.
He said it’s equally important to note that some men with prostate cancer may choose treatment even if they have a limited longevity.
“Not all patients will choose conservative management, even if it is recommended by guidelines. However, they need to be given the opportunity to make a good decision for themselves with the best possible data,” Daskivich said.
This work was supported in part by a US Department of VA Merit Review. Daskivich reported receiving personal fees from the Medical Education Speakers Network, EDAP, and RAND; research support from Lantheus and Janssen; and a patent pending for a system for healthcare visit quality assessment outside the submitted work. Schoenborn, Walter, and Anderson had no relevant disclosures.
A version of this article first appeared on Medscape.com.
Oral Microbiome Dysbiosis: Biomarker for Upper GI Disorders?
TOPLINE:
Dysbiosis of the oral microbiome is associated with various upper gastrointestinal (UGI) disorders and precancerous lesions, with specific microbial signatures varying by disease and oral site, research shows.
METHODOLOGY:
- Emerging evidence suggests that the oral microbiota may contribute to the development of gastrointestinal malignancies, leading to efforts to identify biomarkers for early detection and progress of disease.
- In this population-based cross-sectional study, researchers studied the association between the microbiome of saliva, subgingival, and buccal mucosa and UGI disorders, particularly precancerous lesions.
- Participants included 388 adults who underwent upper endoscopy with biopsies for histopathologic analysis.
- UGI symptoms were evaluated using a validated tool, and 16S ribosomal RNA sequencing was used to characterize microbial diversity and composition of 380 saliva, 200 subgingival, and 267 buccal mucosa samples.
TAKEAWAY:
- Saliva dysbiosis was associated with several UGI disorders, including gastroesophageal reflux symptoms alone, symptomatic esophagitis, combined esophagitis and Barrett’s esophagus (BE), Helicobacter pylori–positive histology, chemical reactive gastritis, atrophic H pylori gastritis, and intestinal metaplasia.
- In contrast, dysbiosis in subgingival and buccal mucosa was more specifically associated with BE and atrophic H pylori gastritis.
- Among several identified genera, Prevotella and Fusobacterium in saliva were associated with gastric atrophy and intestinal metaplasia, and in subgingival samples, there was a notable link between Fretibacterium in BE and Fusobacterium in gastric atrophy and intestinal metaplasia.
IN PRACTICE:
“Our study for the first time suggests that microbiota in the subgingival and buccal regions may serve as more specific biomarkers for detecting precancerous lesions in asymptomatic patients, particularly for Barrett’s esophagus,” the authors wrote. “Saliva might be more appropriate for monitoring any UGI disorders at the population level.”
SOURCE:
The study, with first author Fatemeh Sadeghi, PhD, with Karolinska Institutet, Stockholm, Sweden, was published online in the American Journal of Gastroenterology.
LIMITATIONS:
The study used bacterial DNA, which cannot distinguish metabolically active bacteria. Data on diet and probiotic use were not collected. The cross-sectional design precludes conclusions about causality.
DISCLOSURES:
The authors declared no conflicts of interest. The study was funded by the Swedish Cancer Society and the Swedish Research Council.
A version of this article first appeared on Medscape.com.
TOPLINE:
Dysbiosis of the oral microbiome is associated with various upper gastrointestinal (UGI) disorders and precancerous lesions, with specific microbial signatures varying by disease and oral site, research shows.
METHODOLOGY:
- Emerging evidence suggests that the oral microbiota may contribute to the development of gastrointestinal malignancies, leading to efforts to identify biomarkers for early detection and progress of disease.
- In this population-based cross-sectional study, researchers studied the association between the microbiome of saliva, subgingival, and buccal mucosa and UGI disorders, particularly precancerous lesions.
- Participants included 388 adults who underwent upper endoscopy with biopsies for histopathologic analysis.
- UGI symptoms were evaluated using a validated tool, and 16S ribosomal RNA sequencing was used to characterize microbial diversity and composition of 380 saliva, 200 subgingival, and 267 buccal mucosa samples.
TAKEAWAY:
- Saliva dysbiosis was associated with several UGI disorders, including gastroesophageal reflux symptoms alone, symptomatic esophagitis, combined esophagitis and Barrett’s esophagus (BE), Helicobacter pylori–positive histology, chemical reactive gastritis, atrophic H pylori gastritis, and intestinal metaplasia.
- In contrast, dysbiosis in subgingival and buccal mucosa was more specifically associated with BE and atrophic H pylori gastritis.
- Among several identified genera, Prevotella and Fusobacterium in saliva were associated with gastric atrophy and intestinal metaplasia, and in subgingival samples, there was a notable link between Fretibacterium in BE and Fusobacterium in gastric atrophy and intestinal metaplasia.
IN PRACTICE:
“Our study for the first time suggests that microbiota in the subgingival and buccal regions may serve as more specific biomarkers for detecting precancerous lesions in asymptomatic patients, particularly for Barrett’s esophagus,” the authors wrote. “Saliva might be more appropriate for monitoring any UGI disorders at the population level.”
SOURCE:
The study, with first author Fatemeh Sadeghi, PhD, with Karolinska Institutet, Stockholm, Sweden, was published online in the American Journal of Gastroenterology.
LIMITATIONS:
The study used bacterial DNA, which cannot distinguish metabolically active bacteria. Data on diet and probiotic use were not collected. The cross-sectional design precludes conclusions about causality.
DISCLOSURES:
The authors declared no conflicts of interest. The study was funded by the Swedish Cancer Society and the Swedish Research Council.
A version of this article first appeared on Medscape.com.
TOPLINE:
Dysbiosis of the oral microbiome is associated with various upper gastrointestinal (UGI) disorders and precancerous lesions, with specific microbial signatures varying by disease and oral site, research shows.
METHODOLOGY:
- Emerging evidence suggests that the oral microbiota may contribute to the development of gastrointestinal malignancies, leading to efforts to identify biomarkers for early detection and progress of disease.
- In this population-based cross-sectional study, researchers studied the association between the microbiome of saliva, subgingival, and buccal mucosa and UGI disorders, particularly precancerous lesions.
- Participants included 388 adults who underwent upper endoscopy with biopsies for histopathologic analysis.
- UGI symptoms were evaluated using a validated tool, and 16S ribosomal RNA sequencing was used to characterize microbial diversity and composition of 380 saliva, 200 subgingival, and 267 buccal mucosa samples.
TAKEAWAY:
- Saliva dysbiosis was associated with several UGI disorders, including gastroesophageal reflux symptoms alone, symptomatic esophagitis, combined esophagitis and Barrett’s esophagus (BE), Helicobacter pylori–positive histology, chemical reactive gastritis, atrophic H pylori gastritis, and intestinal metaplasia.
- In contrast, dysbiosis in subgingival and buccal mucosa was more specifically associated with BE and atrophic H pylori gastritis.
- Among several identified genera, Prevotella and Fusobacterium in saliva were associated with gastric atrophy and intestinal metaplasia, and in subgingival samples, there was a notable link between Fretibacterium in BE and Fusobacterium in gastric atrophy and intestinal metaplasia.
IN PRACTICE:
“Our study for the first time suggests that microbiota in the subgingival and buccal regions may serve as more specific biomarkers for detecting precancerous lesions in asymptomatic patients, particularly for Barrett’s esophagus,” the authors wrote. “Saliva might be more appropriate for monitoring any UGI disorders at the population level.”
SOURCE:
The study, with first author Fatemeh Sadeghi, PhD, with Karolinska Institutet, Stockholm, Sweden, was published online in the American Journal of Gastroenterology.
LIMITATIONS:
The study used bacterial DNA, which cannot distinguish metabolically active bacteria. Data on diet and probiotic use were not collected. The cross-sectional design precludes conclusions about causality.
DISCLOSURES:
The authors declared no conflicts of interest. The study was funded by the Swedish Cancer Society and the Swedish Research Council.
A version of this article first appeared on Medscape.com.
Updated Alzheimer’s Guidelines Chart the Full Diagnostic Journey
This is the first update since 2001 for specialists and the first guideline for primary care physicians. Executive summaries of the guidelines were published in three articles online on December 23 in a special issue of Alzheimer’s & Dementia.
What’s New?
“With this guideline, we expand the scope of prior guidelines by providing recommendations for practicing clinicians on the process from start to finish,” coauthor Brad Dickerson, MD, director of the Massachusetts General Hospital Frontotemporal Disorders Unit and professor of neurology at Harvard Medical School, Boston, said in a statement.
“If clinicians adopt these recommendations and healthcare systems provide adequate resources, outcomes should improve in most patients in most practice settings,” Dickerson added in an interview.
Through a modified-Delphi approach and guideline-development process, an expert workgroup representing primary and specialty care reviewed 7374 publications, of which 133 met inclusion criteria.
Based on the information, the workgroup outlined a three-step patient-centered evaluation process, which includes assessing cognitive functional status, identifying the cognitive-behavioral syndrome based on specific symptoms, and determining the likely brain diseases or conditions causing the symptoms.
What Are the Key Recommendations?
The guidelines include 19 “practical” recommendations that are applicable to any practice setting. They capture the core elements of a high-quality evaluation and disclosure process, the author said. Here is a brief summary of the recommendations:
Initial evaluation: Perform a multitiered evaluation for patients who self-report or whose care partner or clinician reports cognitive, behavioral, or functional changes.
Patient-centered communication: Partner with the patient and/or care partner to establish shared goals for the evaluation process; assess the patient’s capacity to engage in goal setting.
Diagnostic formulation: Use a tiered approach to assessments and tests based on individual presentation, risk factors, and profile, aiming to determine the level of impairment, cognitive-behavioral syndrome, and likely causes and contributing factors.
History taking: Gather reliable information from informants about changes in cognition, activities of daily living, mood, neuropsychiatric symptoms, and sensory/motor functions. Document individualized risk factors for cognitive decline.
Examination: Conduct a comprehensive examination of cognition, mood, behavior, and a dementia-focused neurologic evaluation using validated tools.
Laboratory tests: Perform tiered, individualized laboratory evaluations, starting with routine tests for all patients.
Structural imaging: Obtain structural brain imaging (MRI preferred, CT as an alternative) to help establish a cause.
Ongoing communication: Engage in ongoing dialogue with patient/care partner to guide them throughout the diagnostic process.
Diagnostic disclosure: Share findings honestly and compassionately, explaining the syndrome, its severity, probable cause, prognosis, treatment options and support resources.
Specialist referral: Refer patients with atypical, uncertain, early-onset, or rapidly progressing symptoms to a dementia subspecialist.
Neuropsychological testing: Use in instances of diagnostic uncertainty or patients with complex clinical profiles. At a minimum, the neuropsychological evaluation should include normed neuropsychological testing of the domains of learning and memory (in particular delayed free and cued recall/recognition), attention, executive function, visuospatial function, and language.
Advanced diagnostic testing: When diagnostic uncertainty remains, obtain additional laboratory tests tailored to individual patient profiles.
Molecular imaging: In a patient with an established cognitive-behavioral syndrome in whom there is continued diagnostic uncertainty regarding cause(s) after structural imaging, a dementia specialist can obtain molecular imaging with fluorodeoxyglucose PET to improve diagnostic accuracy.
Cerebrospinal fluid (CSF) analysis: Utilize CSF biomarkers to evaluate amyloid beta and tau profiles in cases with unresolved diagnostic uncertainty.
Amyloid PET imaging: Perform amyloid PET scans for patients with persistent diagnostic uncertainty after other assessments.
Genetic counseling and testing: Consider genetic testing for patients with strong autosomal dominant family histories and involve a genetic counselor.
Future Directions?
Maria C. Carrillo, PhD, chief science officer and medical affairs lead for the Alzheimer’s Association, encourages clinicians to incorporate these guidelines into their practice.
“These guidelines are important because they guide clinicians in the evaluation of memory complaints, which could have many underlying causes. That is the necessary start for an early and accurate Alzheimer’s diagnosis,” Carrillo said in a statement.
Dickerson said the new guidelines do not address blood-based biomarkers “because nobody really feels that they are ready for prime time yet, even though they’re getting rolled out as clinical products.”
However, the recommendations will be revised as needed. “That’s one of the values of setting this up as a process; whenever any new development occurs, it will be easy to update the guidelines to show where that new test or new biomarker fits in the overall process,” he said.
New Appropriate Use Guidance
A separate workgroup, jointly convened by the Alzheimer’s Association and the Society of Nuclear Medicine and Molecular Imaging, has revised appropriate use criteria (AUC) for amyloid PET imaging and developed AUC for tau PET imaging.
They were simultaneously published online in Alzheimer’s & Dementia and The Journal of Nuclear Medicine. They are the first revision since the initial AUC for amyloid PET was introduced in 2013.
“The updated amyloid/tau appropriate use criteria will help ensure these tracers are used in a cost-effective manner and the scan results will be used appropriately to add value to the diagnosis and management of dementia,” said workgroup members Kevin Donohoe, MD, with Beth Israel Deaconess Medical Center, Boston, and Phillip Kuo, MD, with City of Hope National Medical Center, Duarte, California.
The AUC include 17 real-world scenarios in which amyloid or tau PET may be considered, with the two tests considered separately and given their own rating for each scenario.
Overall, the strongest evidence for their use includes assessment and prognosis for people with mild cognitive impairment; assessment of people with dementia when the cause is not clearly known; and determining eligibility for treatment with new disease-modifying therapies, and monitoring response to these treatments, the workgroup said.
“Whereas the prior AUC was written at a time when only the deposition of amyloid could be documented, the new therapeutic agents allow us to demonstrate the actual clearance of amyloid during therapy,” Donohoe and Kuo explained.
“These new therapeutic agents are expensive and, as with most medications, may cause unwanted side effects. The most recent version of the AUC includes information about the appropriate use of amyloid imaging for both documenting the presence of amyloid deposits in the brain, making anti-amyloid therapy an option, as well as documenting the effectiveness of the therapeutic agents as amyloid is (or is not) cleared from the brain,” Donahoe and Kuo noted.
The revised AUC also state that, in most cases, amyloid and tau PET tests should not be used for people who do not have cognitive impairment, even if they carry the APOE4 risk-related gene for Alzheimer’s disease; nonmedical use such as for legal concerns, insurance coverage, or employment screening; and in place of genetic testing in patients suspected of carrying a disease-causing genetic mutation.
In a statement, lead author Gil D. Rabinovici, MD, with University of California, San Francisco, emphasized that the AUC “should be considered guidelines for clinicians, not a substitute for careful clinical judgment that considers the full clinical context for each patient with cognitive complaints.”
This research was funded by the Alzheimer’s Association. Disclosures for guideline authors are available with the original articles.
A version of this article first appeared on Medscape.com.
This is the first update since 2001 for specialists and the first guideline for primary care physicians. Executive summaries of the guidelines were published in three articles online on December 23 in a special issue of Alzheimer’s & Dementia.
What’s New?
“With this guideline, we expand the scope of prior guidelines by providing recommendations for practicing clinicians on the process from start to finish,” coauthor Brad Dickerson, MD, director of the Massachusetts General Hospital Frontotemporal Disorders Unit and professor of neurology at Harvard Medical School, Boston, said in a statement.
“If clinicians adopt these recommendations and healthcare systems provide adequate resources, outcomes should improve in most patients in most practice settings,” Dickerson added in an interview.
Through a modified-Delphi approach and guideline-development process, an expert workgroup representing primary and specialty care reviewed 7374 publications, of which 133 met inclusion criteria.
Based on the information, the workgroup outlined a three-step patient-centered evaluation process, which includes assessing cognitive functional status, identifying the cognitive-behavioral syndrome based on specific symptoms, and determining the likely brain diseases or conditions causing the symptoms.
What Are the Key Recommendations?
The guidelines include 19 “practical” recommendations that are applicable to any practice setting. They capture the core elements of a high-quality evaluation and disclosure process, the author said. Here is a brief summary of the recommendations:
Initial evaluation: Perform a multitiered evaluation for patients who self-report or whose care partner or clinician reports cognitive, behavioral, or functional changes.
Patient-centered communication: Partner with the patient and/or care partner to establish shared goals for the evaluation process; assess the patient’s capacity to engage in goal setting.
Diagnostic formulation: Use a tiered approach to assessments and tests based on individual presentation, risk factors, and profile, aiming to determine the level of impairment, cognitive-behavioral syndrome, and likely causes and contributing factors.
History taking: Gather reliable information from informants about changes in cognition, activities of daily living, mood, neuropsychiatric symptoms, and sensory/motor functions. Document individualized risk factors for cognitive decline.
Examination: Conduct a comprehensive examination of cognition, mood, behavior, and a dementia-focused neurologic evaluation using validated tools.
Laboratory tests: Perform tiered, individualized laboratory evaluations, starting with routine tests for all patients.
Structural imaging: Obtain structural brain imaging (MRI preferred, CT as an alternative) to help establish a cause.
Ongoing communication: Engage in ongoing dialogue with patient/care partner to guide them throughout the diagnostic process.
Diagnostic disclosure: Share findings honestly and compassionately, explaining the syndrome, its severity, probable cause, prognosis, treatment options and support resources.
Specialist referral: Refer patients with atypical, uncertain, early-onset, or rapidly progressing symptoms to a dementia subspecialist.
Neuropsychological testing: Use in instances of diagnostic uncertainty or patients with complex clinical profiles. At a minimum, the neuropsychological evaluation should include normed neuropsychological testing of the domains of learning and memory (in particular delayed free and cued recall/recognition), attention, executive function, visuospatial function, and language.
Advanced diagnostic testing: When diagnostic uncertainty remains, obtain additional laboratory tests tailored to individual patient profiles.
Molecular imaging: In a patient with an established cognitive-behavioral syndrome in whom there is continued diagnostic uncertainty regarding cause(s) after structural imaging, a dementia specialist can obtain molecular imaging with fluorodeoxyglucose PET to improve diagnostic accuracy.
Cerebrospinal fluid (CSF) analysis: Utilize CSF biomarkers to evaluate amyloid beta and tau profiles in cases with unresolved diagnostic uncertainty.
Amyloid PET imaging: Perform amyloid PET scans for patients with persistent diagnostic uncertainty after other assessments.
Genetic counseling and testing: Consider genetic testing for patients with strong autosomal dominant family histories and involve a genetic counselor.
Future Directions?
Maria C. Carrillo, PhD, chief science officer and medical affairs lead for the Alzheimer’s Association, encourages clinicians to incorporate these guidelines into their practice.
“These guidelines are important because they guide clinicians in the evaluation of memory complaints, which could have many underlying causes. That is the necessary start for an early and accurate Alzheimer’s diagnosis,” Carrillo said in a statement.
Dickerson said the new guidelines do not address blood-based biomarkers “because nobody really feels that they are ready for prime time yet, even though they’re getting rolled out as clinical products.”
However, the recommendations will be revised as needed. “That’s one of the values of setting this up as a process; whenever any new development occurs, it will be easy to update the guidelines to show where that new test or new biomarker fits in the overall process,” he said.
New Appropriate Use Guidance
A separate workgroup, jointly convened by the Alzheimer’s Association and the Society of Nuclear Medicine and Molecular Imaging, has revised appropriate use criteria (AUC) for amyloid PET imaging and developed AUC for tau PET imaging.
They were simultaneously published online in Alzheimer’s & Dementia and The Journal of Nuclear Medicine. They are the first revision since the initial AUC for amyloid PET was introduced in 2013.
“The updated amyloid/tau appropriate use criteria will help ensure these tracers are used in a cost-effective manner and the scan results will be used appropriately to add value to the diagnosis and management of dementia,” said workgroup members Kevin Donohoe, MD, with Beth Israel Deaconess Medical Center, Boston, and Phillip Kuo, MD, with City of Hope National Medical Center, Duarte, California.
The AUC include 17 real-world scenarios in which amyloid or tau PET may be considered, with the two tests considered separately and given their own rating for each scenario.
Overall, the strongest evidence for their use includes assessment and prognosis for people with mild cognitive impairment; assessment of people with dementia when the cause is not clearly known; and determining eligibility for treatment with new disease-modifying therapies, and monitoring response to these treatments, the workgroup said.
“Whereas the prior AUC was written at a time when only the deposition of amyloid could be documented, the new therapeutic agents allow us to demonstrate the actual clearance of amyloid during therapy,” Donohoe and Kuo explained.
“These new therapeutic agents are expensive and, as with most medications, may cause unwanted side effects. The most recent version of the AUC includes information about the appropriate use of amyloid imaging for both documenting the presence of amyloid deposits in the brain, making anti-amyloid therapy an option, as well as documenting the effectiveness of the therapeutic agents as amyloid is (or is not) cleared from the brain,” Donahoe and Kuo noted.
The revised AUC also state that, in most cases, amyloid and tau PET tests should not be used for people who do not have cognitive impairment, even if they carry the APOE4 risk-related gene for Alzheimer’s disease; nonmedical use such as for legal concerns, insurance coverage, or employment screening; and in place of genetic testing in patients suspected of carrying a disease-causing genetic mutation.
In a statement, lead author Gil D. Rabinovici, MD, with University of California, San Francisco, emphasized that the AUC “should be considered guidelines for clinicians, not a substitute for careful clinical judgment that considers the full clinical context for each patient with cognitive complaints.”
This research was funded by the Alzheimer’s Association. Disclosures for guideline authors are available with the original articles.
A version of this article first appeared on Medscape.com.
This is the first update since 2001 for specialists and the first guideline for primary care physicians. Executive summaries of the guidelines were published in three articles online on December 23 in a special issue of Alzheimer’s & Dementia.
What’s New?
“With this guideline, we expand the scope of prior guidelines by providing recommendations for practicing clinicians on the process from start to finish,” coauthor Brad Dickerson, MD, director of the Massachusetts General Hospital Frontotemporal Disorders Unit and professor of neurology at Harvard Medical School, Boston, said in a statement.
“If clinicians adopt these recommendations and healthcare systems provide adequate resources, outcomes should improve in most patients in most practice settings,” Dickerson added in an interview.
Through a modified-Delphi approach and guideline-development process, an expert workgroup representing primary and specialty care reviewed 7374 publications, of which 133 met inclusion criteria.
Based on the information, the workgroup outlined a three-step patient-centered evaluation process, which includes assessing cognitive functional status, identifying the cognitive-behavioral syndrome based on specific symptoms, and determining the likely brain diseases or conditions causing the symptoms.
What Are the Key Recommendations?
The guidelines include 19 “practical” recommendations that are applicable to any practice setting. They capture the core elements of a high-quality evaluation and disclosure process, the author said. Here is a brief summary of the recommendations:
Initial evaluation: Perform a multitiered evaluation for patients who self-report or whose care partner or clinician reports cognitive, behavioral, or functional changes.
Patient-centered communication: Partner with the patient and/or care partner to establish shared goals for the evaluation process; assess the patient’s capacity to engage in goal setting.
Diagnostic formulation: Use a tiered approach to assessments and tests based on individual presentation, risk factors, and profile, aiming to determine the level of impairment, cognitive-behavioral syndrome, and likely causes and contributing factors.
History taking: Gather reliable information from informants about changes in cognition, activities of daily living, mood, neuropsychiatric symptoms, and sensory/motor functions. Document individualized risk factors for cognitive decline.
Examination: Conduct a comprehensive examination of cognition, mood, behavior, and a dementia-focused neurologic evaluation using validated tools.
Laboratory tests: Perform tiered, individualized laboratory evaluations, starting with routine tests for all patients.
Structural imaging: Obtain structural brain imaging (MRI preferred, CT as an alternative) to help establish a cause.
Ongoing communication: Engage in ongoing dialogue with patient/care partner to guide them throughout the diagnostic process.
Diagnostic disclosure: Share findings honestly and compassionately, explaining the syndrome, its severity, probable cause, prognosis, treatment options and support resources.
Specialist referral: Refer patients with atypical, uncertain, early-onset, or rapidly progressing symptoms to a dementia subspecialist.
Neuropsychological testing: Use in instances of diagnostic uncertainty or patients with complex clinical profiles. At a minimum, the neuropsychological evaluation should include normed neuropsychological testing of the domains of learning and memory (in particular delayed free and cued recall/recognition), attention, executive function, visuospatial function, and language.
Advanced diagnostic testing: When diagnostic uncertainty remains, obtain additional laboratory tests tailored to individual patient profiles.
Molecular imaging: In a patient with an established cognitive-behavioral syndrome in whom there is continued diagnostic uncertainty regarding cause(s) after structural imaging, a dementia specialist can obtain molecular imaging with fluorodeoxyglucose PET to improve diagnostic accuracy.
Cerebrospinal fluid (CSF) analysis: Utilize CSF biomarkers to evaluate amyloid beta and tau profiles in cases with unresolved diagnostic uncertainty.
Amyloid PET imaging: Perform amyloid PET scans for patients with persistent diagnostic uncertainty after other assessments.
Genetic counseling and testing: Consider genetic testing for patients with strong autosomal dominant family histories and involve a genetic counselor.
Future Directions?
Maria C. Carrillo, PhD, chief science officer and medical affairs lead for the Alzheimer’s Association, encourages clinicians to incorporate these guidelines into their practice.
“These guidelines are important because they guide clinicians in the evaluation of memory complaints, which could have many underlying causes. That is the necessary start for an early and accurate Alzheimer’s diagnosis,” Carrillo said in a statement.
Dickerson said the new guidelines do not address blood-based biomarkers “because nobody really feels that they are ready for prime time yet, even though they’re getting rolled out as clinical products.”
However, the recommendations will be revised as needed. “That’s one of the values of setting this up as a process; whenever any new development occurs, it will be easy to update the guidelines to show where that new test or new biomarker fits in the overall process,” he said.
New Appropriate Use Guidance
A separate workgroup, jointly convened by the Alzheimer’s Association and the Society of Nuclear Medicine and Molecular Imaging, has revised appropriate use criteria (AUC) for amyloid PET imaging and developed AUC for tau PET imaging.
They were simultaneously published online in Alzheimer’s & Dementia and The Journal of Nuclear Medicine. They are the first revision since the initial AUC for amyloid PET was introduced in 2013.
“The updated amyloid/tau appropriate use criteria will help ensure these tracers are used in a cost-effective manner and the scan results will be used appropriately to add value to the diagnosis and management of dementia,” said workgroup members Kevin Donohoe, MD, with Beth Israel Deaconess Medical Center, Boston, and Phillip Kuo, MD, with City of Hope National Medical Center, Duarte, California.
The AUC include 17 real-world scenarios in which amyloid or tau PET may be considered, with the two tests considered separately and given their own rating for each scenario.
Overall, the strongest evidence for their use includes assessment and prognosis for people with mild cognitive impairment; assessment of people with dementia when the cause is not clearly known; and determining eligibility for treatment with new disease-modifying therapies, and monitoring response to these treatments, the workgroup said.
“Whereas the prior AUC was written at a time when only the deposition of amyloid could be documented, the new therapeutic agents allow us to demonstrate the actual clearance of amyloid during therapy,” Donohoe and Kuo explained.
“These new therapeutic agents are expensive and, as with most medications, may cause unwanted side effects. The most recent version of the AUC includes information about the appropriate use of amyloid imaging for both documenting the presence of amyloid deposits in the brain, making anti-amyloid therapy an option, as well as documenting the effectiveness of the therapeutic agents as amyloid is (or is not) cleared from the brain,” Donahoe and Kuo noted.
The revised AUC also state that, in most cases, amyloid and tau PET tests should not be used for people who do not have cognitive impairment, even if they carry the APOE4 risk-related gene for Alzheimer’s disease; nonmedical use such as for legal concerns, insurance coverage, or employment screening; and in place of genetic testing in patients suspected of carrying a disease-causing genetic mutation.
In a statement, lead author Gil D. Rabinovici, MD, with University of California, San Francisco, emphasized that the AUC “should be considered guidelines for clinicians, not a substitute for careful clinical judgment that considers the full clinical context for each patient with cognitive complaints.”
This research was funded by the Alzheimer’s Association. Disclosures for guideline authors are available with the original articles.
A version of this article first appeared on Medscape.com.
FROM ALZHEIMER’S & DEMENTIA
Traumatic Brain Injury May Reactivate Herpes Virus Leading to Neurodegeneration
a new study suggested.
Using a three-dimensional (3D) human brain tissue model, researchers observed that quiescent HSV-1 can be reactivated by a mechanical jolt mimicking concussion, leading to signature markers of Alzheimer’s disease, including neuroinflammation and production of amyloid beta and phosphorylated tau (p-tau) and gliosis — a phenotype made worse by repeated head injury.
“This opens the question as to whether antiviral drugs or anti-inflammatory agents might be useful as early preventive treatments after head trauma to stop HSV-1 activation in its tracks and lower the risk of Alzheimer’s disease,” lead investigator Dana Cairns, PhD, with the Department of Biomedical Engineering at Tufts University, Medford, Massachusetts, said in a statement.
But outside experts urged caution in drawing any firm conclusions, pending further study.
The study was published online in the journal Science Signaling.
HSV-1: A Major Alzheimer’s Disease Risk Factor?
TBI is a major risk factor for Alzheimer’s disease and dementia, but the pathways in the brain leading from TBI to dementia are unknown.
HSV-1 is found in over 80% of people; varicella zoster virus (VZV) is found in about 95%. Both viruses are known to enter the brain and lay dormant in neurons and glial cells. Prior evidence indicates that HSV-1 in the brain of APOE-ε4 carriers confers a strong risk for Alzheimer’s disease.
A number of years ago, the team created a 3D model of human brain tissue to study the link between TBI, the viruses, and dementia. The model is 6 mm wide, shaped like a donut, and made of a spongy material of silk protein and collagen saturated with neural stem cells. The cells mature into neurons, communicate with each other, and form a network that mimics the brain environment.
In an earlier study using the model quiescently infected with HSV-1, Cairns and colleagues found that subsequent exposure to VZV created the inflammatory conditions that led to reactivation of HSV-1.
This led them to wonder what would happen if they subjected the brain tissue model to a physical disruption akin to a concussion. Would HSV-1 wake up and start the process of neurodegeneration?
To investigate, they examined the effects of one or more controlled blows to the 3D human brain tissue model in the absence or presence of quiescent HSV-1 infection.
After repeated, mild controlled blows, researchers found that the latently infected 3D brain tissue displayed reactivated HSV-1 and the production and accumulation of amyloid beta and p-tau — which promotes neurodegeneration. The blows also activated gliosis, which is associated with destructive neuroinflammation.
These effects are collectively associated with Alzheimer’s disease, dementia, and chronic traumatic encephalopathy, they pointed out, and were increased with additional injury but were absent in tissue not infected with HSV-1.
“These data suggest that HSV-1 in the brain is pivotal in increasing the risk of Alzheimer’s disease, as other recent studies using cerebral organoids have suggested,” the researchers wrote.
They propose that following brain injury, “whether by infection or mechanical damage, the resulting inflammation induces HSV-1 reactivation in the brain leading to the development of Alzheimer’s disease/dementia and that HSV-1 is a major cause of the disease, especially in APOE4 carriers.”
Future studies should investigate “possible ways of mitigating or stopping the damage caused by head injury, thereby reducing subsequent development of Alzheimer’s disease by implementing efforts to prevent the reactivation of virus in brain such as anti-inflammatory and/or antiviral treatment post-injury,” researchers suggested.
Outside Experts Weigh in
Several outside experts offered perspective on the study in a statement from the UK nonprofit Science Media Centre.
Tara Spires-Jones, PhD, president of the British Neuroscience Association and group leader at the UK Dementia Research Institute, London, England, said that, while the study is interesting, there are limitations.
“The increase in Alzheimer’s-like brain changes in these latent virus-containing cells subjected to injury does not resemble the pathology that is found in the brain of people with Alzheimer’s disease,” Spires-Jones noted.
“These experiments were also in cells grown in artificial conditions without important Alzheimer’s-related factors such as age and blood vessel changes. Finally, these experiments were repeated in a small number of experimental replicates (three times per experiment), so these results will need to be confirmed in more relevant biological systems with larger studies to be sure there is a biological link between latent herpes simplex virus type 1, brain injury, and Alzheimer’s pathology,” Spires-Jones cautioned.
Robert Howard, MD, MRCPsych, University College London (UCL) Division of Psychiatry, said the study suggests a possible mechanism for the association between HSV-1, brain injury, and Alzheimer’s disease.
“However, as so often in science, it is very important to bear in mind that association does not mean causation. Much more research will be needed before this can be seriously considered a plausible mechanism for the development of dementia,” Howard cautioned.
“Avoidance of brain injuries, such as those encountered in some contact sports, is already known to be an important way to prevent dementia, and I’m unconvinced that this reflects anything more complicated than mechanical damage causing death of brain cells,” he added.
Jennifer Pocock, PhD, with UCL Queen Square Institute of Neurology, noted the role of microglia, which are activated by mild and repetitive TBI, isn’t addressed in the study.
“This paper seems to suggest that only astrocytes contribute to the reported neuroinflammation in brain tissue. Also, the inclusion of APOE3/4 is not clearly defined. Because of this, the findings are likely to represent an over interpretation for the ‘real world’ as the inclusion of microglia may negate or accentuate them, depending on the severity of the TBI,” Pocock said.
The study was funded by the US Army Research Office and Department of Defense. The authors have declared no relevant conflicts of interest. Spires-Jones and Howard had no relevant disclosures related to this study. Pocock has received research funding from AstraZeneca and Daiichi Sankyo.
A version of this article appeared on Medscape.com.
a new study suggested.
Using a three-dimensional (3D) human brain tissue model, researchers observed that quiescent HSV-1 can be reactivated by a mechanical jolt mimicking concussion, leading to signature markers of Alzheimer’s disease, including neuroinflammation and production of amyloid beta and phosphorylated tau (p-tau) and gliosis — a phenotype made worse by repeated head injury.
“This opens the question as to whether antiviral drugs or anti-inflammatory agents might be useful as early preventive treatments after head trauma to stop HSV-1 activation in its tracks and lower the risk of Alzheimer’s disease,” lead investigator Dana Cairns, PhD, with the Department of Biomedical Engineering at Tufts University, Medford, Massachusetts, said in a statement.
But outside experts urged caution in drawing any firm conclusions, pending further study.
The study was published online in the journal Science Signaling.
HSV-1: A Major Alzheimer’s Disease Risk Factor?
TBI is a major risk factor for Alzheimer’s disease and dementia, but the pathways in the brain leading from TBI to dementia are unknown.
HSV-1 is found in over 80% of people; varicella zoster virus (VZV) is found in about 95%. Both viruses are known to enter the brain and lay dormant in neurons and glial cells. Prior evidence indicates that HSV-1 in the brain of APOE-ε4 carriers confers a strong risk for Alzheimer’s disease.
A number of years ago, the team created a 3D model of human brain tissue to study the link between TBI, the viruses, and dementia. The model is 6 mm wide, shaped like a donut, and made of a spongy material of silk protein and collagen saturated with neural stem cells. The cells mature into neurons, communicate with each other, and form a network that mimics the brain environment.
In an earlier study using the model quiescently infected with HSV-1, Cairns and colleagues found that subsequent exposure to VZV created the inflammatory conditions that led to reactivation of HSV-1.
This led them to wonder what would happen if they subjected the brain tissue model to a physical disruption akin to a concussion. Would HSV-1 wake up and start the process of neurodegeneration?
To investigate, they examined the effects of one or more controlled blows to the 3D human brain tissue model in the absence or presence of quiescent HSV-1 infection.
After repeated, mild controlled blows, researchers found that the latently infected 3D brain tissue displayed reactivated HSV-1 and the production and accumulation of amyloid beta and p-tau — which promotes neurodegeneration. The blows also activated gliosis, which is associated with destructive neuroinflammation.
These effects are collectively associated with Alzheimer’s disease, dementia, and chronic traumatic encephalopathy, they pointed out, and were increased with additional injury but were absent in tissue not infected with HSV-1.
“These data suggest that HSV-1 in the brain is pivotal in increasing the risk of Alzheimer’s disease, as other recent studies using cerebral organoids have suggested,” the researchers wrote.
They propose that following brain injury, “whether by infection or mechanical damage, the resulting inflammation induces HSV-1 reactivation in the brain leading to the development of Alzheimer’s disease/dementia and that HSV-1 is a major cause of the disease, especially in APOE4 carriers.”
Future studies should investigate “possible ways of mitigating or stopping the damage caused by head injury, thereby reducing subsequent development of Alzheimer’s disease by implementing efforts to prevent the reactivation of virus in brain such as anti-inflammatory and/or antiviral treatment post-injury,” researchers suggested.
Outside Experts Weigh in
Several outside experts offered perspective on the study in a statement from the UK nonprofit Science Media Centre.
Tara Spires-Jones, PhD, president of the British Neuroscience Association and group leader at the UK Dementia Research Institute, London, England, said that, while the study is interesting, there are limitations.
“The increase in Alzheimer’s-like brain changes in these latent virus-containing cells subjected to injury does not resemble the pathology that is found in the brain of people with Alzheimer’s disease,” Spires-Jones noted.
“These experiments were also in cells grown in artificial conditions without important Alzheimer’s-related factors such as age and blood vessel changes. Finally, these experiments were repeated in a small number of experimental replicates (three times per experiment), so these results will need to be confirmed in more relevant biological systems with larger studies to be sure there is a biological link between latent herpes simplex virus type 1, brain injury, and Alzheimer’s pathology,” Spires-Jones cautioned.
Robert Howard, MD, MRCPsych, University College London (UCL) Division of Psychiatry, said the study suggests a possible mechanism for the association between HSV-1, brain injury, and Alzheimer’s disease.
“However, as so often in science, it is very important to bear in mind that association does not mean causation. Much more research will be needed before this can be seriously considered a plausible mechanism for the development of dementia,” Howard cautioned.
“Avoidance of brain injuries, such as those encountered in some contact sports, is already known to be an important way to prevent dementia, and I’m unconvinced that this reflects anything more complicated than mechanical damage causing death of brain cells,” he added.
Jennifer Pocock, PhD, with UCL Queen Square Institute of Neurology, noted the role of microglia, which are activated by mild and repetitive TBI, isn’t addressed in the study.
“This paper seems to suggest that only astrocytes contribute to the reported neuroinflammation in brain tissue. Also, the inclusion of APOE3/4 is not clearly defined. Because of this, the findings are likely to represent an over interpretation for the ‘real world’ as the inclusion of microglia may negate or accentuate them, depending on the severity of the TBI,” Pocock said.
The study was funded by the US Army Research Office and Department of Defense. The authors have declared no relevant conflicts of interest. Spires-Jones and Howard had no relevant disclosures related to this study. Pocock has received research funding from AstraZeneca and Daiichi Sankyo.
A version of this article appeared on Medscape.com.
a new study suggested.
Using a three-dimensional (3D) human brain tissue model, researchers observed that quiescent HSV-1 can be reactivated by a mechanical jolt mimicking concussion, leading to signature markers of Alzheimer’s disease, including neuroinflammation and production of amyloid beta and phosphorylated tau (p-tau) and gliosis — a phenotype made worse by repeated head injury.
“This opens the question as to whether antiviral drugs or anti-inflammatory agents might be useful as early preventive treatments after head trauma to stop HSV-1 activation in its tracks and lower the risk of Alzheimer’s disease,” lead investigator Dana Cairns, PhD, with the Department of Biomedical Engineering at Tufts University, Medford, Massachusetts, said in a statement.
But outside experts urged caution in drawing any firm conclusions, pending further study.
The study was published online in the journal Science Signaling.
HSV-1: A Major Alzheimer’s Disease Risk Factor?
TBI is a major risk factor for Alzheimer’s disease and dementia, but the pathways in the brain leading from TBI to dementia are unknown.
HSV-1 is found in over 80% of people; varicella zoster virus (VZV) is found in about 95%. Both viruses are known to enter the brain and lay dormant in neurons and glial cells. Prior evidence indicates that HSV-1 in the brain of APOE-ε4 carriers confers a strong risk for Alzheimer’s disease.
A number of years ago, the team created a 3D model of human brain tissue to study the link between TBI, the viruses, and dementia. The model is 6 mm wide, shaped like a donut, and made of a spongy material of silk protein and collagen saturated with neural stem cells. The cells mature into neurons, communicate with each other, and form a network that mimics the brain environment.
In an earlier study using the model quiescently infected with HSV-1, Cairns and colleagues found that subsequent exposure to VZV created the inflammatory conditions that led to reactivation of HSV-1.
This led them to wonder what would happen if they subjected the brain tissue model to a physical disruption akin to a concussion. Would HSV-1 wake up and start the process of neurodegeneration?
To investigate, they examined the effects of one or more controlled blows to the 3D human brain tissue model in the absence or presence of quiescent HSV-1 infection.
After repeated, mild controlled blows, researchers found that the latently infected 3D brain tissue displayed reactivated HSV-1 and the production and accumulation of amyloid beta and p-tau — which promotes neurodegeneration. The blows also activated gliosis, which is associated with destructive neuroinflammation.
These effects are collectively associated with Alzheimer’s disease, dementia, and chronic traumatic encephalopathy, they pointed out, and were increased with additional injury but were absent in tissue not infected with HSV-1.
“These data suggest that HSV-1 in the brain is pivotal in increasing the risk of Alzheimer’s disease, as other recent studies using cerebral organoids have suggested,” the researchers wrote.
They propose that following brain injury, “whether by infection or mechanical damage, the resulting inflammation induces HSV-1 reactivation in the brain leading to the development of Alzheimer’s disease/dementia and that HSV-1 is a major cause of the disease, especially in APOE4 carriers.”
Future studies should investigate “possible ways of mitigating or stopping the damage caused by head injury, thereby reducing subsequent development of Alzheimer’s disease by implementing efforts to prevent the reactivation of virus in brain such as anti-inflammatory and/or antiviral treatment post-injury,” researchers suggested.
Outside Experts Weigh in
Several outside experts offered perspective on the study in a statement from the UK nonprofit Science Media Centre.
Tara Spires-Jones, PhD, president of the British Neuroscience Association and group leader at the UK Dementia Research Institute, London, England, said that, while the study is interesting, there are limitations.
“The increase in Alzheimer’s-like brain changes in these latent virus-containing cells subjected to injury does not resemble the pathology that is found in the brain of people with Alzheimer’s disease,” Spires-Jones noted.
“These experiments were also in cells grown in artificial conditions without important Alzheimer’s-related factors such as age and blood vessel changes. Finally, these experiments were repeated in a small number of experimental replicates (three times per experiment), so these results will need to be confirmed in more relevant biological systems with larger studies to be sure there is a biological link between latent herpes simplex virus type 1, brain injury, and Alzheimer’s pathology,” Spires-Jones cautioned.
Robert Howard, MD, MRCPsych, University College London (UCL) Division of Psychiatry, said the study suggests a possible mechanism for the association between HSV-1, brain injury, and Alzheimer’s disease.
“However, as so often in science, it is very important to bear in mind that association does not mean causation. Much more research will be needed before this can be seriously considered a plausible mechanism for the development of dementia,” Howard cautioned.
“Avoidance of brain injuries, such as those encountered in some contact sports, is already known to be an important way to prevent dementia, and I’m unconvinced that this reflects anything more complicated than mechanical damage causing death of brain cells,” he added.
Jennifer Pocock, PhD, with UCL Queen Square Institute of Neurology, noted the role of microglia, which are activated by mild and repetitive TBI, isn’t addressed in the study.
“This paper seems to suggest that only astrocytes contribute to the reported neuroinflammation in brain tissue. Also, the inclusion of APOE3/4 is not clearly defined. Because of this, the findings are likely to represent an over interpretation for the ‘real world’ as the inclusion of microglia may negate or accentuate them, depending on the severity of the TBI,” Pocock said.
The study was funded by the US Army Research Office and Department of Defense. The authors have declared no relevant conflicts of interest. Spires-Jones and Howard had no relevant disclosures related to this study. Pocock has received research funding from AstraZeneca and Daiichi Sankyo.
A version of this article appeared on Medscape.com.
FROM SCIENCE SIGNALING
Major Depression in Older Adults Tied to Risky Driving Behaviors
Older adults with major depressive disorder (MDD) exhibit riskier driving behaviors, compared with their nondepressed peers, including hard braking, cornering, and unpredictable driving patterns, new research showed.
Data for the study came from commercial vehicle data trackers installed in participants’ vehicles. After about a year of follow-up, the investigators found that MDD was associated with an increase in the amount and severity of risking driving, even after they controlled for antidepressant use.
Late-life depression often goes undiagnosed, and the new findings highlight the importance of routine depression screening and targeted interventions to ensure driving safety among older adults, the study team said.
“By using longitudinal, real-world driving data rather than controlled settings or self-reports, the study provides robust evidence of how MDD influences driving behaviors in day-to-day contexts,” first author Ganesh M. Babulal, PhD, OTD, with the Department of Neurology, Washington University School of Medicine in St Louis, Missouri, said in an interview.
“By analyzing the influence of antidepressant use and overall medication load, the study disentangles the effects of MDD from those of driver-impairing medications, further clarifying the unique contributions of depression to driving behaviors,” Babulal noted.
The study was published online in JAMA Network Open.
Road Risks
As the number of older adults grows, safe driving practices in this age group become increasingly crucial. By 2050, one quarter of drivers in the United States will be older than 65 years. MDD affects about 8% of US adults and is linked to cognitive impairments that may compromise driving safety.
Prior studies revealed a link between depression and increased car crash risk, regardless of age. And earlier research by Babulal and colleagues showed that older adults with depression were three times more likely to receive a marginal or failing score on a standardized road test.
To further study the issue, Babulal and colleagues examined the impact of MDD on naturalistic driving behaviors among older adults using longitudinal data.
Participants were recruited from the Driving Real-World In-Vehicle Evaluation System Project, where their daily driving behaviors were recorded using commercial vehicle data loggers installed in their personal vehicles.
The cohort included 85 adults with MDD (mean age, 69 years; 71% women) and 310 adults without MDD (mean age, 70 years; 49% women). The majority of participants in both groups were non-Hispanic White individuals.
Based on intercepts, adults with MDD had a propensity toward riskier driving habits with a higher frequency of speeding events and spending more time on the road than those without MDD, they found.
During a mean of 1.1 years of follow-up, compared with older adults without MDD, those with MDD exhibited significantly more hard braking (P < .001) and hard cornering events per trip (P = .04) over time. They also traveled farther from home and visited more unique destinations (P < .001 for both).
Over time, older adults also displayed increased entropy in driving patterns (P < .001), indicated less predictable driving routes.
“Driving unpredictability, as evidenced by increased random entropy, highlights the unique challenges posed by MDD in maintaining safe driving practices,” the researchers wrote.
Adjustment for antidepressant use, which could impair driving, or total medication burden did not change the findings, suggesting MDD independently affects driving.
“Most importantly, our findings demonstrate that MDD — a common and treatable illness in older adults — was associated with an increase in both the amount and magnitude of risky driving behaviors over time,” the researchers wrote.
The researchers noted that the study did not account for changes in depression severity over time and other psychiatric conditions co-occurring with MDD were not adjusted for. Also, situational factors like weather or traffic conditions were not assessed.
Clear Clinical Implications
There is a “pressing need” for targeted interventions to manage and mitigate the driving risks associated with late-life depression, the researchers wrote.
“The study emphasizes the need for interventions tailored to the mental health and driving behaviors of older adults. These could include cognitive retraining, driver rehabilitation programs, and routine depression screening to enhance road safety and preserve independence,” Babulal said.
“Encouraging older adults with MDD to self-regulate their driving habits (eg, avoiding night driving or high-traffic situations) and educating them about potential driving challenges related to their condition can enhance safety,” he added.
Commenting on this study, Ipsit Vahia, MD, McLean Hospital, Belmont, Massachusetts, and Harvard Medical School, Boston, Massachusetts, said it “adds nuance to our understanding of how depression can impact driving among older adults.
“While the connection between depression and a higher incident of crashes is known, this study demonstrates an association with riskier driving behaviors such as speeding,” Vahia said. “It highlights the importance of clinicians proactively initiating discussion of driving and safety when working with older adults with depressive symptoms.”
This work was funded by grants from the National Institutes of Health and National Institute on Aging. Babulal had no relevant disclosures. Vahia had served as a consultant for Otsuka.
A version of this article appeared on Medscape.com.
Older adults with major depressive disorder (MDD) exhibit riskier driving behaviors, compared with their nondepressed peers, including hard braking, cornering, and unpredictable driving patterns, new research showed.
Data for the study came from commercial vehicle data trackers installed in participants’ vehicles. After about a year of follow-up, the investigators found that MDD was associated with an increase in the amount and severity of risking driving, even after they controlled for antidepressant use.
Late-life depression often goes undiagnosed, and the new findings highlight the importance of routine depression screening and targeted interventions to ensure driving safety among older adults, the study team said.
“By using longitudinal, real-world driving data rather than controlled settings or self-reports, the study provides robust evidence of how MDD influences driving behaviors in day-to-day contexts,” first author Ganesh M. Babulal, PhD, OTD, with the Department of Neurology, Washington University School of Medicine in St Louis, Missouri, said in an interview.
“By analyzing the influence of antidepressant use and overall medication load, the study disentangles the effects of MDD from those of driver-impairing medications, further clarifying the unique contributions of depression to driving behaviors,” Babulal noted.
The study was published online in JAMA Network Open.
Road Risks
As the number of older adults grows, safe driving practices in this age group become increasingly crucial. By 2050, one quarter of drivers in the United States will be older than 65 years. MDD affects about 8% of US adults and is linked to cognitive impairments that may compromise driving safety.
Prior studies revealed a link between depression and increased car crash risk, regardless of age. And earlier research by Babulal and colleagues showed that older adults with depression were three times more likely to receive a marginal or failing score on a standardized road test.
To further study the issue, Babulal and colleagues examined the impact of MDD on naturalistic driving behaviors among older adults using longitudinal data.
Participants were recruited from the Driving Real-World In-Vehicle Evaluation System Project, where their daily driving behaviors were recorded using commercial vehicle data loggers installed in their personal vehicles.
The cohort included 85 adults with MDD (mean age, 69 years; 71% women) and 310 adults without MDD (mean age, 70 years; 49% women). The majority of participants in both groups were non-Hispanic White individuals.
Based on intercepts, adults with MDD had a propensity toward riskier driving habits with a higher frequency of speeding events and spending more time on the road than those without MDD, they found.
During a mean of 1.1 years of follow-up, compared with older adults without MDD, those with MDD exhibited significantly more hard braking (P < .001) and hard cornering events per trip (P = .04) over time. They also traveled farther from home and visited more unique destinations (P < .001 for both).
Over time, older adults also displayed increased entropy in driving patterns (P < .001), indicated less predictable driving routes.
“Driving unpredictability, as evidenced by increased random entropy, highlights the unique challenges posed by MDD in maintaining safe driving practices,” the researchers wrote.
Adjustment for antidepressant use, which could impair driving, or total medication burden did not change the findings, suggesting MDD independently affects driving.
“Most importantly, our findings demonstrate that MDD — a common and treatable illness in older adults — was associated with an increase in both the amount and magnitude of risky driving behaviors over time,” the researchers wrote.
The researchers noted that the study did not account for changes in depression severity over time and other psychiatric conditions co-occurring with MDD were not adjusted for. Also, situational factors like weather or traffic conditions were not assessed.
Clear Clinical Implications
There is a “pressing need” for targeted interventions to manage and mitigate the driving risks associated with late-life depression, the researchers wrote.
“The study emphasizes the need for interventions tailored to the mental health and driving behaviors of older adults. These could include cognitive retraining, driver rehabilitation programs, and routine depression screening to enhance road safety and preserve independence,” Babulal said.
“Encouraging older adults with MDD to self-regulate their driving habits (eg, avoiding night driving or high-traffic situations) and educating them about potential driving challenges related to their condition can enhance safety,” he added.
Commenting on this study, Ipsit Vahia, MD, McLean Hospital, Belmont, Massachusetts, and Harvard Medical School, Boston, Massachusetts, said it “adds nuance to our understanding of how depression can impact driving among older adults.
“While the connection between depression and a higher incident of crashes is known, this study demonstrates an association with riskier driving behaviors such as speeding,” Vahia said. “It highlights the importance of clinicians proactively initiating discussion of driving and safety when working with older adults with depressive symptoms.”
This work was funded by grants from the National Institutes of Health and National Institute on Aging. Babulal had no relevant disclosures. Vahia had served as a consultant for Otsuka.
A version of this article appeared on Medscape.com.
Older adults with major depressive disorder (MDD) exhibit riskier driving behaviors, compared with their nondepressed peers, including hard braking, cornering, and unpredictable driving patterns, new research showed.
Data for the study came from commercial vehicle data trackers installed in participants’ vehicles. After about a year of follow-up, the investigators found that MDD was associated with an increase in the amount and severity of risking driving, even after they controlled for antidepressant use.
Late-life depression often goes undiagnosed, and the new findings highlight the importance of routine depression screening and targeted interventions to ensure driving safety among older adults, the study team said.
“By using longitudinal, real-world driving data rather than controlled settings or self-reports, the study provides robust evidence of how MDD influences driving behaviors in day-to-day contexts,” first author Ganesh M. Babulal, PhD, OTD, with the Department of Neurology, Washington University School of Medicine in St Louis, Missouri, said in an interview.
“By analyzing the influence of antidepressant use and overall medication load, the study disentangles the effects of MDD from those of driver-impairing medications, further clarifying the unique contributions of depression to driving behaviors,” Babulal noted.
The study was published online in JAMA Network Open.
Road Risks
As the number of older adults grows, safe driving practices in this age group become increasingly crucial. By 2050, one quarter of drivers in the United States will be older than 65 years. MDD affects about 8% of US adults and is linked to cognitive impairments that may compromise driving safety.
Prior studies revealed a link between depression and increased car crash risk, regardless of age. And earlier research by Babulal and colleagues showed that older adults with depression were three times more likely to receive a marginal or failing score on a standardized road test.
To further study the issue, Babulal and colleagues examined the impact of MDD on naturalistic driving behaviors among older adults using longitudinal data.
Participants were recruited from the Driving Real-World In-Vehicle Evaluation System Project, where their daily driving behaviors were recorded using commercial vehicle data loggers installed in their personal vehicles.
The cohort included 85 adults with MDD (mean age, 69 years; 71% women) and 310 adults without MDD (mean age, 70 years; 49% women). The majority of participants in both groups were non-Hispanic White individuals.
Based on intercepts, adults with MDD had a propensity toward riskier driving habits with a higher frequency of speeding events and spending more time on the road than those without MDD, they found.
During a mean of 1.1 years of follow-up, compared with older adults without MDD, those with MDD exhibited significantly more hard braking (P < .001) and hard cornering events per trip (P = .04) over time. They also traveled farther from home and visited more unique destinations (P < .001 for both).
Over time, older adults also displayed increased entropy in driving patterns (P < .001), indicated less predictable driving routes.
“Driving unpredictability, as evidenced by increased random entropy, highlights the unique challenges posed by MDD in maintaining safe driving practices,” the researchers wrote.
Adjustment for antidepressant use, which could impair driving, or total medication burden did not change the findings, suggesting MDD independently affects driving.
“Most importantly, our findings demonstrate that MDD — a common and treatable illness in older adults — was associated with an increase in both the amount and magnitude of risky driving behaviors over time,” the researchers wrote.
The researchers noted that the study did not account for changes in depression severity over time and other psychiatric conditions co-occurring with MDD were not adjusted for. Also, situational factors like weather or traffic conditions were not assessed.
Clear Clinical Implications
There is a “pressing need” for targeted interventions to manage and mitigate the driving risks associated with late-life depression, the researchers wrote.
“The study emphasizes the need for interventions tailored to the mental health and driving behaviors of older adults. These could include cognitive retraining, driver rehabilitation programs, and routine depression screening to enhance road safety and preserve independence,” Babulal said.
“Encouraging older adults with MDD to self-regulate their driving habits (eg, avoiding night driving or high-traffic situations) and educating them about potential driving challenges related to their condition can enhance safety,” he added.
Commenting on this study, Ipsit Vahia, MD, McLean Hospital, Belmont, Massachusetts, and Harvard Medical School, Boston, Massachusetts, said it “adds nuance to our understanding of how depression can impact driving among older adults.
“While the connection between depression and a higher incident of crashes is known, this study demonstrates an association with riskier driving behaviors such as speeding,” Vahia said. “It highlights the importance of clinicians proactively initiating discussion of driving and safety when working with older adults with depressive symptoms.”
This work was funded by grants from the National Institutes of Health and National Institute on Aging. Babulal had no relevant disclosures. Vahia had served as a consultant for Otsuka.
A version of this article appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Americans’ Top Causes of Anxiety Revealed
What current events are keeping Americans up at night? The economy, gun violence, and hate crimes top the list, results from a newly released American Psychiatric Association (APA) survey showed.
Anxiety about international conflicts — namely, the Russia-Ukraine and Israel-Hamas wars — also remains high.
“While we like to stay informed, the news can also impact our mental health, and being mindful of that impact is important. If current events seem overwhelming it may be time to limit your news consumption,” APA CEO and Medical Director Marketa M. Wills, MD, MBD, said in a statement.
Survey results also revealed the election and the holidays were common sources of stress.
“Election stress is common, and it’s important to recognize that, as we’re spending more time with family around the holidays, we might need to have a strategy to manage our own mental health during these times,” Howard Liu, MD, MBA, chair of the Department of Psychiatry, University of Nebraska Medical Center, Omaha, told this news organization.
“As with any difficult topic, we all have different levels of avoidance or desire to engage, and it’s okay to set boundaries based on past conversations with family. I think sometimes we get drawn into arguments that we don’t want to have or may not be productive for either side,” said Liu, who chairs the APA Council on Communications.
In line with trends throughout 2024, adults polled by the APA in November were most anxious about the economy (75%), gun violence (64%), and hate crimes (60%). The survey included 2200 US adults as part of the APA’s Healthy Minds monthly series.
Anxiety about international conflicts remained high in November at 57% — but was down from 65% in August.
Election anxiety remained high in mid-November but not as high as before the election. In August, 72% of Americans said they were anxious about the 2024 election. In November, just after the election, 50% reported anxiety over the election outcome.
“I think the anticipation of change can sometimes be worse than the change itself. So I think a lot of people are now taking the attitude of — let’s wait and see what actually happens,” said Liu.
Half the adults (50%) anticipate the same amount of stress as the 2023 holiday season, while almost one third expect more stress (28%), and one fourth anticipate less stress (23%).
When asked how the holidays generally affect their mental health, 38% said it has positive effects, and 21% said the opposite was true.
Anxiety About the Future
After a divisive election, most Americans were ready to avoid politics at holiday gatherings, results of a separate poll conducted by the American Psychological Association in late November showed.
That poll, which included 2000 US adults, showed that more than 7 in 10 (72%) said they wanted to avoid talking about politics with family and friends over the holidays.
In addition, nearly two in five adults (39%) reported they were stressed by the thought of politics being raised at holiday gatherings and would try to avoid family members they disagree with. Younger adults were significantly more likely than were their older counterparts to report they planned to avoid family over the holidays.
The future of the nation also weighs on the minds of many Americans.
Another poll conducted by the American Psychological Association in August prior to the 2024 US presidential election showed that 77% of respondents said the future of the nation was a significant source of stress for them.
In the postelection poll, more than one third of adults (35%) said they are more stressed about the future of the nation now than they were leading up to the election, and another third reported they are now less stressed (32%). A quarter of adults (24%) said their stress about the future of the nation was unchanged, and 9% said they were not stressed about the future of the nation then or now.
“There’s still clearly a lot of uncertainty, and there’s a lot of activity right now for the president-elect,” which can contribute to anxiety, C. Vaile Wright, PhD, psychologist, researcher and spokesperson for the American Psychological Association, told this news organization.
These data also show that many Americans have little or no trust in the government, with some wanting to leave the United States.
“It’s a reflection of the lack of strong leadership across the board in this country. We have a governmental system in place that does not seem to serve the people, but to serve corporations and maintenance of power. I think people are disillusioned with it and that creates a lack of trust and hopelessness,” Wright noted.
Liu and Wright reported no relevant disclosures.
A version of this article appeared on Medscape.com.
What current events are keeping Americans up at night? The economy, gun violence, and hate crimes top the list, results from a newly released American Psychiatric Association (APA) survey showed.
Anxiety about international conflicts — namely, the Russia-Ukraine and Israel-Hamas wars — also remains high.
“While we like to stay informed, the news can also impact our mental health, and being mindful of that impact is important. If current events seem overwhelming it may be time to limit your news consumption,” APA CEO and Medical Director Marketa M. Wills, MD, MBD, said in a statement.
Survey results also revealed the election and the holidays were common sources of stress.
“Election stress is common, and it’s important to recognize that, as we’re spending more time with family around the holidays, we might need to have a strategy to manage our own mental health during these times,” Howard Liu, MD, MBA, chair of the Department of Psychiatry, University of Nebraska Medical Center, Omaha, told this news organization.
“As with any difficult topic, we all have different levels of avoidance or desire to engage, and it’s okay to set boundaries based on past conversations with family. I think sometimes we get drawn into arguments that we don’t want to have or may not be productive for either side,” said Liu, who chairs the APA Council on Communications.
In line with trends throughout 2024, adults polled by the APA in November were most anxious about the economy (75%), gun violence (64%), and hate crimes (60%). The survey included 2200 US adults as part of the APA’s Healthy Minds monthly series.
Anxiety about international conflicts remained high in November at 57% — but was down from 65% in August.
Election anxiety remained high in mid-November but not as high as before the election. In August, 72% of Americans said they were anxious about the 2024 election. In November, just after the election, 50% reported anxiety over the election outcome.
“I think the anticipation of change can sometimes be worse than the change itself. So I think a lot of people are now taking the attitude of — let’s wait and see what actually happens,” said Liu.
Half the adults (50%) anticipate the same amount of stress as the 2023 holiday season, while almost one third expect more stress (28%), and one fourth anticipate less stress (23%).
When asked how the holidays generally affect their mental health, 38% said it has positive effects, and 21% said the opposite was true.
Anxiety About the Future
After a divisive election, most Americans were ready to avoid politics at holiday gatherings, results of a separate poll conducted by the American Psychological Association in late November showed.
That poll, which included 2000 US adults, showed that more than 7 in 10 (72%) said they wanted to avoid talking about politics with family and friends over the holidays.
In addition, nearly two in five adults (39%) reported they were stressed by the thought of politics being raised at holiday gatherings and would try to avoid family members they disagree with. Younger adults were significantly more likely than were their older counterparts to report they planned to avoid family over the holidays.
The future of the nation also weighs on the minds of many Americans.
Another poll conducted by the American Psychological Association in August prior to the 2024 US presidential election showed that 77% of respondents said the future of the nation was a significant source of stress for them.
In the postelection poll, more than one third of adults (35%) said they are more stressed about the future of the nation now than they were leading up to the election, and another third reported they are now less stressed (32%). A quarter of adults (24%) said their stress about the future of the nation was unchanged, and 9% said they were not stressed about the future of the nation then or now.
“There’s still clearly a lot of uncertainty, and there’s a lot of activity right now for the president-elect,” which can contribute to anxiety, C. Vaile Wright, PhD, psychologist, researcher and spokesperson for the American Psychological Association, told this news organization.
These data also show that many Americans have little or no trust in the government, with some wanting to leave the United States.
“It’s a reflection of the lack of strong leadership across the board in this country. We have a governmental system in place that does not seem to serve the people, but to serve corporations and maintenance of power. I think people are disillusioned with it and that creates a lack of trust and hopelessness,” Wright noted.
Liu and Wright reported no relevant disclosures.
A version of this article appeared on Medscape.com.
What current events are keeping Americans up at night? The economy, gun violence, and hate crimes top the list, results from a newly released American Psychiatric Association (APA) survey showed.
Anxiety about international conflicts — namely, the Russia-Ukraine and Israel-Hamas wars — also remains high.
“While we like to stay informed, the news can also impact our mental health, and being mindful of that impact is important. If current events seem overwhelming it may be time to limit your news consumption,” APA CEO and Medical Director Marketa M. Wills, MD, MBD, said in a statement.
Survey results also revealed the election and the holidays were common sources of stress.
“Election stress is common, and it’s important to recognize that, as we’re spending more time with family around the holidays, we might need to have a strategy to manage our own mental health during these times,” Howard Liu, MD, MBA, chair of the Department of Psychiatry, University of Nebraska Medical Center, Omaha, told this news organization.
“As with any difficult topic, we all have different levels of avoidance or desire to engage, and it’s okay to set boundaries based on past conversations with family. I think sometimes we get drawn into arguments that we don’t want to have or may not be productive for either side,” said Liu, who chairs the APA Council on Communications.
In line with trends throughout 2024, adults polled by the APA in November were most anxious about the economy (75%), gun violence (64%), and hate crimes (60%). The survey included 2200 US adults as part of the APA’s Healthy Minds monthly series.
Anxiety about international conflicts remained high in November at 57% — but was down from 65% in August.
Election anxiety remained high in mid-November but not as high as before the election. In August, 72% of Americans said they were anxious about the 2024 election. In November, just after the election, 50% reported anxiety over the election outcome.
“I think the anticipation of change can sometimes be worse than the change itself. So I think a lot of people are now taking the attitude of — let’s wait and see what actually happens,” said Liu.
Half the adults (50%) anticipate the same amount of stress as the 2023 holiday season, while almost one third expect more stress (28%), and one fourth anticipate less stress (23%).
When asked how the holidays generally affect their mental health, 38% said it has positive effects, and 21% said the opposite was true.
Anxiety About the Future
After a divisive election, most Americans were ready to avoid politics at holiday gatherings, results of a separate poll conducted by the American Psychological Association in late November showed.
That poll, which included 2000 US adults, showed that more than 7 in 10 (72%) said they wanted to avoid talking about politics with family and friends over the holidays.
In addition, nearly two in five adults (39%) reported they were stressed by the thought of politics being raised at holiday gatherings and would try to avoid family members they disagree with. Younger adults were significantly more likely than were their older counterparts to report they planned to avoid family over the holidays.
The future of the nation also weighs on the minds of many Americans.
Another poll conducted by the American Psychological Association in August prior to the 2024 US presidential election showed that 77% of respondents said the future of the nation was a significant source of stress for them.
In the postelection poll, more than one third of adults (35%) said they are more stressed about the future of the nation now than they were leading up to the election, and another third reported they are now less stressed (32%). A quarter of adults (24%) said their stress about the future of the nation was unchanged, and 9% said they were not stressed about the future of the nation then or now.
“There’s still clearly a lot of uncertainty, and there’s a lot of activity right now for the president-elect,” which can contribute to anxiety, C. Vaile Wright, PhD, psychologist, researcher and spokesperson for the American Psychological Association, told this news organization.
These data also show that many Americans have little or no trust in the government, with some wanting to leave the United States.
“It’s a reflection of the lack of strong leadership across the board in this country. We have a governmental system in place that does not seem to serve the people, but to serve corporations and maintenance of power. I think people are disillusioned with it and that creates a lack of trust and hopelessness,” Wright noted.
Liu and Wright reported no relevant disclosures.
A version of this article appeared on Medscape.com.