Leading a healthy lifestyle, including regular exercise, eating fruits and vegetables, and minimal alcohol consumption, is associated with better cognitive function in older adults, new research showed.

The study, which combined longitudinal and cohort data with postmortem brain pathology reports, found that the association held even in those with Alzheimer’s disease (AD) pathology, suggesting that lifestyle factors may provide cognitive reserve and improve cognitive abilities in older age.

“While we must use caution in interpreting our findings, in part due to its cross-sectional design, these results support the role of lifestyle in providing cognitive reserve to maintain cognitive function in older adults despite the accumulation of common dementia-related brain pathologies,” Klodian Dhana, MD, of the Rush University Medical Center in Chicago, Illinois, and colleagues wrote.

The study was published online in JAMA Neurology.
 

Better Cognition

The study included 586 participants (71% female) who were followed from 1997 until 2022 as part of the Rush Memory and Aging Project longitudinal cohort study.

Investigators collected information on lifestyle and demographic factors at regular intervals, as well as information on diet, alcohol intake, and time spent participating in moderate or vigorous physical activity such as gardening, walking, calisthenics, biking, or swimming. Participants also received annual cognitive tests.

In later years, participants answered questions about whether they played card games or checkers, read, visited a museum, or did other cognitively stimulating activities.

Postmortem exams allowed the researchers to assess brain pathology (mean age at death, 91 years).

Participants were categorized as living a healthy lifestyle if they scored well in five categories: They exercised moderately or vigorously for 150 minutes per week, did not smoke, consumed one to two drinks per week, regularly played card games or did puzzles, and followed the Mediterranean-DASH Diet Intervention for Neurodegenerative Delay diet.

For every one-point increase in the healthy lifestyle score, there were 0.120 fewer units of beta-amyloid load in the brain and a 0.22 standardized unit higher score in cognitive performance (P < .001).

After adjusting for the beta-amyloid load, phosphorated tau tangle, or other dementia-related brain pathologies, the healthy lifestyle score remained independently associated with cognition (P < .001).

More than 88% of a person’s global cognition score was a “direct association of lifestyle,” investigators noted, leaving slightly less than 12% affected by the presence of beta-amyloid.

“The mechanistic link between lifestyle and cognition could be attributed in part to the antioxidant and anti-inflammatory capacities of each lifestyle factor (eg, nutrition and physical activity) and cognitive reserve (eg, cognitive activities) that contribute to less inflammation and oxidative stress,” the authors wrote.

Further studies are necessary, they added, especially research investigating the association of lifestyle factors with markers for inflammation to understand the mechanisms of how lifestyle is associated with better cognitive scores in old age.

Study limitations include the reliance on self-reported data because cognitive impairment could interfere with inaccurate reporting. In addition, the authors noted that cognitive abilities may affect adherence to lifestyle factors.
 

‘Important Evidence’

In an accompanying editorial, Yue Leng, MD, and Kristine Yaffe, MD, of the University of San Francisco in San Francisco, California, noted that the new study adds “important evidence” to the debate over modifiable risk factors and reduction of AD risk.

“These interesting results add strength to the concept that health and lifestyle factors are important strategies for prevention and suggest that several mechanisms may be at work,” they wrote, adding that the study is “one of the first to harness brain pathology to investigate these mechanisms and is a crucial step forward in addressing these important questions.”

Still, critical questions remain regarding the mechanistic pathways linking modifiable risk factors and cognitive aging, Drs. Leng and Yaffe wrote.

“There is an urgent need for more well-designed randomized controlled trials to pave the way for dementia risk reduction in the era of precision medicine,” they wrote. “These strategies should be offered in conjunction with AD medications, similar to the approach in cardiovascular disease prevention and treatment in which medications along with lifestyle strategies are the standard of care.”

The study was funded by the National Institute on Aging. Dr. Dhana reported grants paid to his institution from the Alzheimer’s Association. No other disclosures were reported.

A version of this article appeared on Medscape.com.

Leading a healthy lifestyle, including regular exercise, eating fruits and vegetables, and minimal alcohol consumption, is associated with better cognitive function in older adults, new research showed.

The study, which combined longitudinal and cohort data with postmortem brain pathology reports, found that the association held even in those with Alzheimer’s disease (AD) pathology, suggesting that lifestyle factors may provide cognitive reserve and improve cognitive abilities in older age.

“While we must use caution in interpreting our findings, in part due to its cross-sectional design, these results support the role of lifestyle in providing cognitive reserve to maintain cognitive function in older adults despite the accumulation of common dementia-related brain pathologies,” Klodian Dhana, MD, of the Rush University Medical Center in Chicago, Illinois, and colleagues wrote.

The study was published online in JAMA Neurology.
 

Better Cognition

The study included 586 participants (71% female) who were followed from 1997 until 2022 as part of the Rush Memory and Aging Project longitudinal cohort study.

Investigators collected information on lifestyle and demographic factors at regular intervals, as well as information on diet, alcohol intake, and time spent participating in moderate or vigorous physical activity such as gardening, walking, calisthenics, biking, or swimming. Participants also received annual cognitive tests.

In later years, participants answered questions about whether they played card games or checkers, read, visited a museum, or did other cognitively stimulating activities.

Postmortem exams allowed the researchers to assess brain pathology (mean age at death, 91 years).

Participants were categorized as living a healthy lifestyle if they scored well in five categories: They exercised moderately or vigorously for 150 minutes per week, did not smoke, consumed one to two drinks per week, regularly played card games or did puzzles, and followed the Mediterranean-DASH Diet Intervention for Neurodegenerative Delay diet.

For every one-point increase in the healthy lifestyle score, there were 0.120 fewer units of beta-amyloid load in the brain and a 0.22 standardized unit higher score in cognitive performance (P < .001).

After adjusting for the beta-amyloid load, phosphorated tau tangle, or other dementia-related brain pathologies, the healthy lifestyle score remained independently associated with cognition (P < .001).

More than 88% of a person’s global cognition score was a “direct association of lifestyle,” investigators noted, leaving slightly less than 12% affected by the presence of beta-amyloid.

“The mechanistic link between lifestyle and cognition could be attributed in part to the antioxidant and anti-inflammatory capacities of each lifestyle factor (eg, nutrition and physical activity) and cognitive reserve (eg, cognitive activities) that contribute to less inflammation and oxidative stress,” the authors wrote.

Further studies are necessary, they added, especially research investigating the association of lifestyle factors with markers for inflammation to understand the mechanisms of how lifestyle is associated with better cognitive scores in old age.

Study limitations include the reliance on self-reported data because cognitive impairment could interfere with inaccurate reporting. In addition, the authors noted that cognitive abilities may affect adherence to lifestyle factors.
 

‘Important Evidence’

In an accompanying editorial, Yue Leng, MD, and Kristine Yaffe, MD, of the University of San Francisco in San Francisco, California, noted that the new study adds “important evidence” to the debate over modifiable risk factors and reduction of AD risk.

“These interesting results add strength to the concept that health and lifestyle factors are important strategies for prevention and suggest that several mechanisms may be at work,” they wrote, adding that the study is “one of the first to harness brain pathology to investigate these mechanisms and is a crucial step forward in addressing these important questions.”

Still, critical questions remain regarding the mechanistic pathways linking modifiable risk factors and cognitive aging, Drs. Leng and Yaffe wrote.

“There is an urgent need for more well-designed randomized controlled trials to pave the way for dementia risk reduction in the era of precision medicine,” they wrote. “These strategies should be offered in conjunction with AD medications, similar to the approach in cardiovascular disease prevention and treatment in which medications along with lifestyle strategies are the standard of care.”

The study was funded by the National Institute on Aging. Dr. Dhana reported grants paid to his institution from the Alzheimer’s Association. No other disclosures were reported.

A version of this article appeared on Medscape.com.

Leading a healthy lifestyle, including regular exercise, eating fruits and vegetables, and minimal alcohol consumption, is associated with better cognitive function in older adults, new research showed.

The study, which combined longitudinal and cohort data with postmortem brain pathology reports, found that the association held even in those with Alzheimer’s disease (AD) pathology, suggesting that lifestyle factors may provide cognitive reserve and improve cognitive abilities in older age.

“While we must use caution in interpreting our findings, in part due to its cross-sectional design, these results support the role of lifestyle in providing cognitive reserve to maintain cognitive function in older adults despite the accumulation of common dementia-related brain pathologies,” Klodian Dhana, MD, of the Rush University Medical Center in Chicago, Illinois, and colleagues wrote.

The study was published online in JAMA Neurology.
 

Better Cognition

The study included 586 participants (71% female) who were followed from 1997 until 2022 as part of the Rush Memory and Aging Project longitudinal cohort study.

Investigators collected information on lifestyle and demographic factors at regular intervals, as well as information on diet, alcohol intake, and time spent participating in moderate or vigorous physical activity such as gardening, walking, calisthenics, biking, or swimming. Participants also received annual cognitive tests.

In later years, participants answered questions about whether they played card games or checkers, read, visited a museum, or did other cognitively stimulating activities.

Postmortem exams allowed the researchers to assess brain pathology (mean age at death, 91 years).

Participants were categorized as living a healthy lifestyle if they scored well in five categories: They exercised moderately or vigorously for 150 minutes per week, did not smoke, consumed one to two drinks per week, regularly played card games or did puzzles, and followed the Mediterranean-DASH Diet Intervention for Neurodegenerative Delay diet.

For every one-point increase in the healthy lifestyle score, there were 0.120 fewer units of beta-amyloid load in the brain and a 0.22 standardized unit higher score in cognitive performance (P < .001).

After adjusting for the beta-amyloid load, phosphorated tau tangle, or other dementia-related brain pathologies, the healthy lifestyle score remained independently associated with cognition (P < .001).

More than 88% of a person’s global cognition score was a “direct association of lifestyle,” investigators noted, leaving slightly less than 12% affected by the presence of beta-amyloid.

“The mechanistic link between lifestyle and cognition could be attributed in part to the antioxidant and anti-inflammatory capacities of each lifestyle factor (eg, nutrition and physical activity) and cognitive reserve (eg, cognitive activities) that contribute to less inflammation and oxidative stress,” the authors wrote.

Further studies are necessary, they added, especially research investigating the association of lifestyle factors with markers for inflammation to understand the mechanisms of how lifestyle is associated with better cognitive scores in old age.

Study limitations include the reliance on self-reported data because cognitive impairment could interfere with inaccurate reporting. In addition, the authors noted that cognitive abilities may affect adherence to lifestyle factors.
 

‘Important Evidence’

In an accompanying editorial, Yue Leng, MD, and Kristine Yaffe, MD, of the University of San Francisco in San Francisco, California, noted that the new study adds “important evidence” to the debate over modifiable risk factors and reduction of AD risk.

“These interesting results add strength to the concept that health and lifestyle factors are important strategies for prevention and suggest that several mechanisms may be at work,” they wrote, adding that the study is “one of the first to harness brain pathology to investigate these mechanisms and is a crucial step forward in addressing these important questions.”

Still, critical questions remain regarding the mechanistic pathways linking modifiable risk factors and cognitive aging, Drs. Leng and Yaffe wrote.

“There is an urgent need for more well-designed randomized controlled trials to pave the way for dementia risk reduction in the era of precision medicine,” they wrote. “These strategies should be offered in conjunction with AD medications, similar to the approach in cardiovascular disease prevention and treatment in which medications along with lifestyle strategies are the standard of care.”

The study was funded by the National Institute on Aging. Dr. Dhana reported grants paid to his institution from the Alzheimer’s Association. No other disclosures were reported.

A version of this article appeared on Medscape.com.

Using a new system for classifying established prognostic features of lymph nodes may lead to better staging of oral cavity squamous cell cancer (OSCC) than the TNM staging system, experts say.

The TNM staging system is used by most facilities for cancer reporting, as defined by the National Cancer Institute. This system combines the size and extent of the primary tumor (T), the number of neighboring lymph nodes with cancer and subcategories (N), and whether or not metastasis has occurred (M).

In a new study published in the journal Cancer, the researchers created a novel classification system to better account for extranodal extension (ENE). The study population included 1460 adults with OSCC (696 with no lymph node involvement and 764 with positive lymph nodes), who underwent surgical resections at four centers.

“Our findings build on the growing evidence base that historical factors do not improve staging performance and that their omission results in improved N‐classification [i.e., the nodal status or lymph node involvement in cancer staging] performance,” John R. de Almeida, MD, of the University of Toronto, and colleagues, wrote in their new paper.

For patients with OSCC, this system, known as the 8th edition of American Joint Committee on Cancer/International Union Against Cancer TNM N‐classification (TNM‐8‐N), has several limitations, the researchers explained. These limitations include redundancy in the rare N3a category (i.e., having single or multiple lymph nodes greater than 6 cm or 3-7 lymph nodes without ENE) and the impact of ENE as a new prognostic feature, they said.

“Recent studies have shown that major ENE is associated with a significantly worse outcome than minor ENE, suggesting that these two subgroups should be considered as separate entities,” the authors wrote.
 

Study Methods and Results

The researchers created N-classifications based on adjusted hazard ratios and statistical analysis (recursive partitioning) with a focus on lymph node (LN) size and number and the extent of ENE. They compared their classifications of OSCC cases to those of the TNM-8-N’s classifications of the same cases.

Using the new classification system, lymph node number and size and the extent of ENE were associated with overall survival. The adjusted hazard ratios for LN counts of 1 vs. zero and greater than 1 vs. 0 were 1.92 and 3.21, respectively. The adjusted hazard ratios (aHRs) for LN size of greater than 3 cm vs. 3 cm or less, and for major vs. minor ENE were 1.88 and 1.40, respectively.

The use of an aHR improved cancer staging compared to the TNM-8-N by eliminating the N2c and 6-cm threshold, stratifying the extent of ENE, and stratifying N2b by 3-cm threshold, the researchers wrote.

The researchers compared their new system to the TNM-8 and also two other classification systems and their own recursive partitioning analysis (another statistical model).

The aHR-based system ranked first out of five in terms of correctly staging cancer, while the TNM-8 was fifth in the discovery cohort and fifth in the validation cohorts.

Outcome predictions (percentage variance explained) were 19.81 with the aHR vs. 18.95 in theTNM-8 in the discovery cohort, and similarly were 11.72 vs. 10.13, respectively, in the validation cohort.

“Overall, 25 patients staged as IVa in TNM‐8 were upstaged to IVb in the aHR proposal, and one patient staged as IVb was downstaged to IVa. Otherwise, overall stage between TNM‐8 and aHR remained the same,” the authors wrote.

“Our proposed N-classification based on aHR challenges previous tenets such as the importance of the 6-cm threshold and the importance of contralateral nodes,” the researchers wrote in their discussion.

The results from the new classification system were limited by the relatively small sample sizes and may not generalize to nonsquamous oral cancers, the researchers noted.

Further validation is needed before this system may be routinely applied in practice, but the results support evidence in favor of eliminating historical factors from staging, they said.
 

Experts Tout Advantages of Proposed Classification System

Cancer staging must be as accurate as possible and reviewed frequently, Shawn Li, MD, an otolaryngologist at University Hospitals, Cleveland, said in an interview. “This study aims to optimize nodal staging in oral cavity cancer. The current staging system doesn’t reflect updated data, and may not be specific enough to oral cavity cancers.”

This study notes the importance of stratifying extranodal extension (ENE) by micro (less than 2 mm) and macro (greater than 2 mm),” he said. It also points out that metastatic disease greater than 6 cm without ENE is infrequent enough not to require its own subcategory, he said.

Finally, in the new classification, proposed in this paper, “N2c was removed, because, statistically, it doesn’t seem to be a worse prognosis in cancers of the oral cavity,” he said.

“The data [described in this new paper] suggests that certain traditional criteria used in nodal staging for oral cavity cancer, such as [involving] very large lymph nodes greater than 6 cm in size and contralateral nodal involvement, may be less important than criteria that have not as of yet been incorporated into head and neck staging,” Wesley Talcott, MD, said in an interview. “The current study provides evidence that in oral cavity cancer, the prognostic accuracy of staging may improve by dropping these older criteria and incorporating degree of extranodal extension.”

This evidence is apparent in the ranking of the new aHR classification as first of the five strategies compared in the study, said Dr. Talcott, who was not involved in the study.

Highlighting the importance of microscopic vs. macroscopic extension may lead to doctors improving their identification of patients at highest risk for recurrence and refining treatment strategies, suggested Dr. Talcott, MD, a radiation oncologist at Northwell Health, New York, NY. However, a larger dataset is needed to validate the diagnostic accuracy of the authors’ proposed staging system, he said.

The TNM‐8‐N was updated in 2017, Dr. Li noted. “Since this system is widely referenced, it will likely need to be updated again before the changes in this study are widely adopted,” he said.

The study was supported by the National Institutes of Health and the National Cancer Institute. The researchers, Dr. Li, and Dr. Talcott had no financial conflicts to disclose.

Using a new system for classifying established prognostic features of lymph nodes may lead to better staging of oral cavity squamous cell cancer (OSCC) than the TNM staging system, experts say.

The TNM staging system is used by most facilities for cancer reporting, as defined by the National Cancer Institute. This system combines the size and extent of the primary tumor (T), the number of neighboring lymph nodes with cancer and subcategories (N), and whether or not metastasis has occurred (M).

In a new study published in the journal Cancer, the researchers created a novel classification system to better account for extranodal extension (ENE). The study population included 1460 adults with OSCC (696 with no lymph node involvement and 764 with positive lymph nodes), who underwent surgical resections at four centers.

“Our findings build on the growing evidence base that historical factors do not improve staging performance and that their omission results in improved N‐classification [i.e., the nodal status or lymph node involvement in cancer staging] performance,” John R. de Almeida, MD, of the University of Toronto, and colleagues, wrote in their new paper.

For patients with OSCC, this system, known as the 8th edition of American Joint Committee on Cancer/International Union Against Cancer TNM N‐classification (TNM‐8‐N), has several limitations, the researchers explained. These limitations include redundancy in the rare N3a category (i.e., having single or multiple lymph nodes greater than 6 cm or 3-7 lymph nodes without ENE) and the impact of ENE as a new prognostic feature, they said.

“Recent studies have shown that major ENE is associated with a significantly worse outcome than minor ENE, suggesting that these two subgroups should be considered as separate entities,” the authors wrote.
 

Study Methods and Results

The researchers created N-classifications based on adjusted hazard ratios and statistical analysis (recursive partitioning) with a focus on lymph node (LN) size and number and the extent of ENE. They compared their classifications of OSCC cases to those of the TNM-8-N’s classifications of the same cases.

Using the new classification system, lymph node number and size and the extent of ENE were associated with overall survival. The adjusted hazard ratios for LN counts of 1 vs. zero and greater than 1 vs. 0 were 1.92 and 3.21, respectively. The adjusted hazard ratios (aHRs) for LN size of greater than 3 cm vs. 3 cm or less, and for major vs. minor ENE were 1.88 and 1.40, respectively.

The use of an aHR improved cancer staging compared to the TNM-8-N by eliminating the N2c and 6-cm threshold, stratifying the extent of ENE, and stratifying N2b by 3-cm threshold, the researchers wrote.

The researchers compared their new system to the TNM-8 and also two other classification systems and their own recursive partitioning analysis (another statistical model).

The aHR-based system ranked first out of five in terms of correctly staging cancer, while the TNM-8 was fifth in the discovery cohort and fifth in the validation cohorts.

Outcome predictions (percentage variance explained) were 19.81 with the aHR vs. 18.95 in theTNM-8 in the discovery cohort, and similarly were 11.72 vs. 10.13, respectively, in the validation cohort.

“Overall, 25 patients staged as IVa in TNM‐8 were upstaged to IVb in the aHR proposal, and one patient staged as IVb was downstaged to IVa. Otherwise, overall stage between TNM‐8 and aHR remained the same,” the authors wrote.

“Our proposed N-classification based on aHR challenges previous tenets such as the importance of the 6-cm threshold and the importance of contralateral nodes,” the researchers wrote in their discussion.

The results from the new classification system were limited by the relatively small sample sizes and may not generalize to nonsquamous oral cancers, the researchers noted.

Further validation is needed before this system may be routinely applied in practice, but the results support evidence in favor of eliminating historical factors from staging, they said.
 

Experts Tout Advantages of Proposed Classification System

Cancer staging must be as accurate as possible and reviewed frequently, Shawn Li, MD, an otolaryngologist at University Hospitals, Cleveland, said in an interview. “This study aims to optimize nodal staging in oral cavity cancer. The current staging system doesn’t reflect updated data, and may not be specific enough to oral cavity cancers.”

This study notes the importance of stratifying extranodal extension (ENE) by micro (less than 2 mm) and macro (greater than 2 mm),” he said. It also points out that metastatic disease greater than 6 cm without ENE is infrequent enough not to require its own subcategory, he said.

Finally, in the new classification, proposed in this paper, “N2c was removed, because, statistically, it doesn’t seem to be a worse prognosis in cancers of the oral cavity,” he said.

“The data [described in this new paper] suggests that certain traditional criteria used in nodal staging for oral cavity cancer, such as [involving] very large lymph nodes greater than 6 cm in size and contralateral nodal involvement, may be less important than criteria that have not as of yet been incorporated into head and neck staging,” Wesley Talcott, MD, said in an interview. “The current study provides evidence that in oral cavity cancer, the prognostic accuracy of staging may improve by dropping these older criteria and incorporating degree of extranodal extension.”

This evidence is apparent in the ranking of the new aHR classification as first of the five strategies compared in the study, said Dr. Talcott, who was not involved in the study.

Highlighting the importance of microscopic vs. macroscopic extension may lead to doctors improving their identification of patients at highest risk for recurrence and refining treatment strategies, suggested Dr. Talcott, MD, a radiation oncologist at Northwell Health, New York, NY. However, a larger dataset is needed to validate the diagnostic accuracy of the authors’ proposed staging system, he said.

The TNM‐8‐N was updated in 2017, Dr. Li noted. “Since this system is widely referenced, it will likely need to be updated again before the changes in this study are widely adopted,” he said.

The study was supported by the National Institutes of Health and the National Cancer Institute. The researchers, Dr. Li, and Dr. Talcott had no financial conflicts to disclose.

Using a new system for classifying established prognostic features of lymph nodes may lead to better staging of oral cavity squamous cell cancer (OSCC) than the TNM staging system, experts say.

The TNM staging system is used by most facilities for cancer reporting, as defined by the National Cancer Institute. This system combines the size and extent of the primary tumor (T), the number of neighboring lymph nodes with cancer and subcategories (N), and whether or not metastasis has occurred (M).

In a new study published in the journal Cancer, the researchers created a novel classification system to better account for extranodal extension (ENE). The study population included 1460 adults with OSCC (696 with no lymph node involvement and 764 with positive lymph nodes), who underwent surgical resections at four centers.

“Our findings build on the growing evidence base that historical factors do not improve staging performance and that their omission results in improved N‐classification [i.e., the nodal status or lymph node involvement in cancer staging] performance,” John R. de Almeida, MD, of the University of Toronto, and colleagues, wrote in their new paper.

For patients with OSCC, this system, known as the 8th edition of American Joint Committee on Cancer/International Union Against Cancer TNM N‐classification (TNM‐8‐N), has several limitations, the researchers explained. These limitations include redundancy in the rare N3a category (i.e., having single or multiple lymph nodes greater than 6 cm or 3-7 lymph nodes without ENE) and the impact of ENE as a new prognostic feature, they said.

“Recent studies have shown that major ENE is associated with a significantly worse outcome than minor ENE, suggesting that these two subgroups should be considered as separate entities,” the authors wrote.
 

Study Methods and Results

The researchers created N-classifications based on adjusted hazard ratios and statistical analysis (recursive partitioning) with a focus on lymph node (LN) size and number and the extent of ENE. They compared their classifications of OSCC cases to those of the TNM-8-N’s classifications of the same cases.

Using the new classification system, lymph node number and size and the extent of ENE were associated with overall survival. The adjusted hazard ratios for LN counts of 1 vs. zero and greater than 1 vs. 0 were 1.92 and 3.21, respectively. The adjusted hazard ratios (aHRs) for LN size of greater than 3 cm vs. 3 cm or less, and for major vs. minor ENE were 1.88 and 1.40, respectively.

The use of an aHR improved cancer staging compared to the TNM-8-N by eliminating the N2c and 6-cm threshold, stratifying the extent of ENE, and stratifying N2b by 3-cm threshold, the researchers wrote.

The researchers compared their new system to the TNM-8 and also two other classification systems and their own recursive partitioning analysis (another statistical model).

The aHR-based system ranked first out of five in terms of correctly staging cancer, while the TNM-8 was fifth in the discovery cohort and fifth in the validation cohorts.

Outcome predictions (percentage variance explained) were 19.81 with the aHR vs. 18.95 in theTNM-8 in the discovery cohort, and similarly were 11.72 vs. 10.13, respectively, in the validation cohort.

“Overall, 25 patients staged as IVa in TNM‐8 were upstaged to IVb in the aHR proposal, and one patient staged as IVb was downstaged to IVa. Otherwise, overall stage between TNM‐8 and aHR remained the same,” the authors wrote.

“Our proposed N-classification based on aHR challenges previous tenets such as the importance of the 6-cm threshold and the importance of contralateral nodes,” the researchers wrote in their discussion.

The results from the new classification system were limited by the relatively small sample sizes and may not generalize to nonsquamous oral cancers, the researchers noted.

Further validation is needed before this system may be routinely applied in practice, but the results support evidence in favor of eliminating historical factors from staging, they said.
 

Experts Tout Advantages of Proposed Classification System

Cancer staging must be as accurate as possible and reviewed frequently, Shawn Li, MD, an otolaryngologist at University Hospitals, Cleveland, said in an interview. “This study aims to optimize nodal staging in oral cavity cancer. The current staging system doesn’t reflect updated data, and may not be specific enough to oral cavity cancers.”

This study notes the importance of stratifying extranodal extension (ENE) by micro (less than 2 mm) and macro (greater than 2 mm),” he said. It also points out that metastatic disease greater than 6 cm without ENE is infrequent enough not to require its own subcategory, he said.

Finally, in the new classification, proposed in this paper, “N2c was removed, because, statistically, it doesn’t seem to be a worse prognosis in cancers of the oral cavity,” he said.

“The data [described in this new paper] suggests that certain traditional criteria used in nodal staging for oral cavity cancer, such as [involving] very large lymph nodes greater than 6 cm in size and contralateral nodal involvement, may be less important than criteria that have not as of yet been incorporated into head and neck staging,” Wesley Talcott, MD, said in an interview. “The current study provides evidence that in oral cavity cancer, the prognostic accuracy of staging may improve by dropping these older criteria and incorporating degree of extranodal extension.”

This evidence is apparent in the ranking of the new aHR classification as first of the five strategies compared in the study, said Dr. Talcott, who was not involved in the study.

Highlighting the importance of microscopic vs. macroscopic extension may lead to doctors improving their identification of patients at highest risk for recurrence and refining treatment strategies, suggested Dr. Talcott, MD, a radiation oncologist at Northwell Health, New York, NY. However, a larger dataset is needed to validate the diagnostic accuracy of the authors’ proposed staging system, he said.

The TNM‐8‐N was updated in 2017, Dr. Li noted. “Since this system is widely referenced, it will likely need to be updated again before the changes in this study are widely adopted,” he said.

The study was supported by the National Institutes of Health and the National Cancer Institute. The researchers, Dr. Li, and Dr. Talcott had no financial conflicts to disclose.

LAS VEGAS — In the treatment of inflammatory bowel disease, combinations of biologics or a biologic and tofacitinib appear to be generally safe and effective, according to a new systematic review and meta-analysis. The study updates a meta-analysis published in 2022, which included 13 studies. The new work included 23 studies that looked at 8 different combinations.

There is a potential concern that the high adverse event rates seen in biologics could be compounded when they are used in combination, according to Ali Osman, MD, who presented the results at a poster session at the annual Crohn’s & Colitis Congress^®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. “Theoretically, you should have more side effects or more serious side effects, but interestingly we didn’t find major side effects. I think the key message is that the combinations of biologic agents are promising in terms of efficacy. In terms of adverse events, it doesn’t lead to major adverse events,” said Dr. Osman, an instructor at Washington University School of Medicine in St. Louis.

Washington University School of Medicine

Although the study did not directly compare the combinations, it did find potential differences in efficacy. “Our most effective [combination] in terms of response and remission was a combination of ustekinumab and an anti-TNF agent with a combined rate of 81.6%. Our lowest adverse events rate were [with the combination of] tofacitinib and vedolizumab,” said Dr. Osman.

The research is a useful update, according to David T. Rubin, MD, AGAF, who was asked for comment. “This has been explored before, but this is a nice effort to describe and try to compare studies of combination biological therapies or biologicals combined with [the JAK inhibitor]. This is to further explore the efforts being made to break the therapeutic ceiling by combining mechanisms, treat IBD and extra-intestinal manifestations with multiple agents simultaneously, and to explore novel treatment strategies,” said Dr. Rubin, professor of medicine and director of the Inflammatory Bowel Disease Center at University of Chicago Medicine.

He noted that the meta-analysis is limited by heterogeneity among the studies, many of which were case series that had been re-analyzed. The update included some prospective proof-of-concept studies of interest that were not in the earlier meta-analysis, including VEGA (anti-IL13 guselkumab plus anti-TNF golimumab versus either drug alone), and EXPLORER (vedolizumab, adalimumab, methotrexate), as well as a study of infliximab combined with natalizumab.

“We await the ongoing prospective trials of dual targeted therapies and novel designs for a future that will undoubtedly include thoughtful and rational combinations,” said Dr. Rubin.

The review included 23 studies that had a minimum of two patients who were treated with a combination of two biologics or a biologic and tofacitinib. The biologics included the anti-TNF antibodies adalimumab, certolizumab pegol, golimumab, and infliximab; as well as guselkumab, natalizumab, ustekinumab, and vedolizumab. Overall, the studies included 531 patients who underwent 543 therapeutic trials, using 8 different combinations.

The highest pooled clinical response observed was 81.6% with ustekinumab combined with an anti-TNF agent (P = .04, 9 studies, 44 therapeutic trials), which also had the highest remission rate of 64.2% (P = .03).

For the treatment of Crohn’s disease, the highest pooled clinical response and remission rates were also seen with ustekinumab combined with an anti-TNF agent (8 studies, 29 therapeutic trials), at 91.6% (P = .28). In ulcerative colitis, vedolizumab plus ustekinumab had the highest pooled clinical response rate at 100.0% (P = 1.00; 4 studies, 4 treatment trials) and ustekinumab plus an anti-TNF agent F at 100.0% (P = 1.00; 4 studies, 5 treatment trials).

Tofacitinib combined with vedolizumab had the lower adverse event rate (12.5%; P = .10; 8 studies, 76 treatment trials) followed by ustekinumab and an anti-TNF agent (12.7%; P = .08; 9 studies, 43 treatment trials) and tofacitinib plus anti-TNF (13.0%; 6 studies, 27 treatment trials).

Other combinations included guselkumab plus ant-TNF (1 study; clinical response, 69.0%), natalizumab plus an anti-TNF agent (1 study, clinical response, 36.5%), tofacitinib plus an anti-TNF agent (5 studies, clinical response, 71.6%), tofacitinib plus ustekinumab (5 studies, clinical response, 70.8%), tofacitinib plus vedolizumab (8 studies, clinical response, 52.7%), vedolizumab plus an anti-TNF agent (13 studies, clinical response, 62.8%), and vedolizumab plus ustekinumab (12 studies, clinical response, 79.3%).

Dr. Osman has no relevant financial conflicts of interest. Dr. Rubin has received grant support from Takeda, and has served as a consultant for Abbvie, Bristol-Myers Squibb, Janssen Pharmaceuticals, Lilly, Pfizer, and Takeda.

LAS VEGAS — In the treatment of inflammatory bowel disease, combinations of biologics or a biologic and tofacitinib appear to be generally safe and effective, according to a new systematic review and meta-analysis. The study updates a meta-analysis published in 2022, which included 13 studies. The new work included 23 studies that looked at 8 different combinations.

There is a potential concern that the high adverse event rates seen in biologics could be compounded when they are used in combination, according to Ali Osman, MD, who presented the results at a poster session at the annual Crohn’s & Colitis Congress^®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. “Theoretically, you should have more side effects or more serious side effects, but interestingly we didn’t find major side effects. I think the key message is that the combinations of biologic agents are promising in terms of efficacy. In terms of adverse events, it doesn’t lead to major adverse events,” said Dr. Osman, an instructor at Washington University School of Medicine in St. Louis.

Washington University School of Medicine

Although the study did not directly compare the combinations, it did find potential differences in efficacy. “Our most effective [combination] in terms of response and remission was a combination of ustekinumab and an anti-TNF agent with a combined rate of 81.6%. Our lowest adverse events rate were [with the combination of] tofacitinib and vedolizumab,” said Dr. Osman.

The research is a useful update, according to David T. Rubin, MD, AGAF, who was asked for comment. “This has been explored before, but this is a nice effort to describe and try to compare studies of combination biological therapies or biologicals combined with [the JAK inhibitor]. This is to further explore the efforts being made to break the therapeutic ceiling by combining mechanisms, treat IBD and extra-intestinal manifestations with multiple agents simultaneously, and to explore novel treatment strategies,” said Dr. Rubin, professor of medicine and director of the Inflammatory Bowel Disease Center at University of Chicago Medicine.

He noted that the meta-analysis is limited by heterogeneity among the studies, many of which were case series that had been re-analyzed. The update included some prospective proof-of-concept studies of interest that were not in the earlier meta-analysis, including VEGA (anti-IL13 guselkumab plus anti-TNF golimumab versus either drug alone), and EXPLORER (vedolizumab, adalimumab, methotrexate), as well as a study of infliximab combined with natalizumab.

“We await the ongoing prospective trials of dual targeted therapies and novel designs for a future that will undoubtedly include thoughtful and rational combinations,” said Dr. Rubin.

The review included 23 studies that had a minimum of two patients who were treated with a combination of two biologics or a biologic and tofacitinib. The biologics included the anti-TNF antibodies adalimumab, certolizumab pegol, golimumab, and infliximab; as well as guselkumab, natalizumab, ustekinumab, and vedolizumab. Overall, the studies included 531 patients who underwent 543 therapeutic trials, using 8 different combinations.

The highest pooled clinical response observed was 81.6% with ustekinumab combined with an anti-TNF agent (P = .04, 9 studies, 44 therapeutic trials), which also had the highest remission rate of 64.2% (P = .03).

For the treatment of Crohn’s disease, the highest pooled clinical response and remission rates were also seen with ustekinumab combined with an anti-TNF agent (8 studies, 29 therapeutic trials), at 91.6% (P = .28). In ulcerative colitis, vedolizumab plus ustekinumab had the highest pooled clinical response rate at 100.0% (P = 1.00; 4 studies, 4 treatment trials) and ustekinumab plus an anti-TNF agent F at 100.0% (P = 1.00; 4 studies, 5 treatment trials).

Tofacitinib combined with vedolizumab had the lower adverse event rate (12.5%; P = .10; 8 studies, 76 treatment trials) followed by ustekinumab and an anti-TNF agent (12.7%; P = .08; 9 studies, 43 treatment trials) and tofacitinib plus anti-TNF (13.0%; 6 studies, 27 treatment trials).

Other combinations included guselkumab plus ant-TNF (1 study; clinical response, 69.0%), natalizumab plus an anti-TNF agent (1 study, clinical response, 36.5%), tofacitinib plus an anti-TNF agent (5 studies, clinical response, 71.6%), tofacitinib plus ustekinumab (5 studies, clinical response, 70.8%), tofacitinib plus vedolizumab (8 studies, clinical response, 52.7%), vedolizumab plus an anti-TNF agent (13 studies, clinical response, 62.8%), and vedolizumab plus ustekinumab (12 studies, clinical response, 79.3%).

Dr. Osman has no relevant financial conflicts of interest. Dr. Rubin has received grant support from Takeda, and has served as a consultant for Abbvie, Bristol-Myers Squibb, Janssen Pharmaceuticals, Lilly, Pfizer, and Takeda.

LAS VEGAS — In the treatment of inflammatory bowel disease, combinations of biologics or a biologic and tofacitinib appear to be generally safe and effective, according to a new systematic review and meta-analysis. The study updates a meta-analysis published in 2022, which included 13 studies. The new work included 23 studies that looked at 8 different combinations.

There is a potential concern that the high adverse event rates seen in biologics could be compounded when they are used in combination, according to Ali Osman, MD, who presented the results at a poster session at the annual Crohn’s & Colitis Congress^®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. “Theoretically, you should have more side effects or more serious side effects, but interestingly we didn’t find major side effects. I think the key message is that the combinations of biologic agents are promising in terms of efficacy. In terms of adverse events, it doesn’t lead to major adverse events,” said Dr. Osman, an instructor at Washington University School of Medicine in St. Louis.

Washington University School of Medicine

Although the study did not directly compare the combinations, it did find potential differences in efficacy. “Our most effective [combination] in terms of response and remission was a combination of ustekinumab and an anti-TNF agent with a combined rate of 81.6%. Our lowest adverse events rate were [with the combination of] tofacitinib and vedolizumab,” said Dr. Osman.

The research is a useful update, according to David T. Rubin, MD, AGAF, who was asked for comment. “This has been explored before, but this is a nice effort to describe and try to compare studies of combination biological therapies or biologicals combined with [the JAK inhibitor]. This is to further explore the efforts being made to break the therapeutic ceiling by combining mechanisms, treat IBD and extra-intestinal manifestations with multiple agents simultaneously, and to explore novel treatment strategies,” said Dr. Rubin, professor of medicine and director of the Inflammatory Bowel Disease Center at University of Chicago Medicine.

He noted that the meta-analysis is limited by heterogeneity among the studies, many of which were case series that had been re-analyzed. The update included some prospective proof-of-concept studies of interest that were not in the earlier meta-analysis, including VEGA (anti-IL13 guselkumab plus anti-TNF golimumab versus either drug alone), and EXPLORER (vedolizumab, adalimumab, methotrexate), as well as a study of infliximab combined with natalizumab.

“We await the ongoing prospective trials of dual targeted therapies and novel designs for a future that will undoubtedly include thoughtful and rational combinations,” said Dr. Rubin.

The review included 23 studies that had a minimum of two patients who were treated with a combination of two biologics or a biologic and tofacitinib. The biologics included the anti-TNF antibodies adalimumab, certolizumab pegol, golimumab, and infliximab; as well as guselkumab, natalizumab, ustekinumab, and vedolizumab. Overall, the studies included 531 patients who underwent 543 therapeutic trials, using 8 different combinations.

The highest pooled clinical response observed was 81.6% with ustekinumab combined with an anti-TNF agent (P = .04, 9 studies, 44 therapeutic trials), which also had the highest remission rate of 64.2% (P = .03).

For the treatment of Crohn’s disease, the highest pooled clinical response and remission rates were also seen with ustekinumab combined with an anti-TNF agent (8 studies, 29 therapeutic trials), at 91.6% (P = .28). In ulcerative colitis, vedolizumab plus ustekinumab had the highest pooled clinical response rate at 100.0% (P = 1.00; 4 studies, 4 treatment trials) and ustekinumab plus an anti-TNF agent F at 100.0% (P = 1.00; 4 studies, 5 treatment trials).

Tofacitinib combined with vedolizumab had the lower adverse event rate (12.5%; P = .10; 8 studies, 76 treatment trials) followed by ustekinumab and an anti-TNF agent (12.7%; P = .08; 9 studies, 43 treatment trials) and tofacitinib plus anti-TNF (13.0%; 6 studies, 27 treatment trials).

Other combinations included guselkumab plus ant-TNF (1 study; clinical response, 69.0%), natalizumab plus an anti-TNF agent (1 study, clinical response, 36.5%), tofacitinib plus an anti-TNF agent (5 studies, clinical response, 71.6%), tofacitinib plus ustekinumab (5 studies, clinical response, 70.8%), tofacitinib plus vedolizumab (8 studies, clinical response, 52.7%), vedolizumab plus an anti-TNF agent (13 studies, clinical response, 62.8%), and vedolizumab plus ustekinumab (12 studies, clinical response, 79.3%).

Dr. Osman has no relevant financial conflicts of interest. Dr. Rubin has received grant support from Takeda, and has served as a consultant for Abbvie, Bristol-Myers Squibb, Janssen Pharmaceuticals, Lilly, Pfizer, and Takeda.

A study from the University of Texas demonstrates the feasibility of using robotic single-port laparoscopy in nipple-sparing mastectomy (NSM), a type of conservative mastectomy preserving the skin and nipple-areola complex. The new findings potentially expand the application of robotic surgery to a larger patient population but doubts about the safety of this approach linger.

Robotic Mastectomy

The first surgeries involving the Da Vinci robotic surgeon for breast removal date to 2015. Multiport robotic surgery faces significant obstacles in this field, however. Feasibility studies have primarily focused on women with small breasts, corresponding to cup size C or smaller.

In the study that was published in JAMA Surgery, surgeons used the more cost-effective single-port platform for bilateral NSM procedures. Among the 20 patients included in the analysis (age, 29-63 years), 11 underwent prophylactic mastectomy (for a high risk for cancer) and 9 had mastectomy for breast tumors. Breast sizes ranged from A cup to D cup.

The duration of the procedure, from skin incision to suture for both breasts, ranged from 205 to 351 minutes (median, 277 minutes). No immediate operative complications (eg, hematoma) occurred, and there was no need for conversion to open surgery in any case. Over the 36-month follow-up, there were no recurrences. About 95% of patients retained skin sensitivity and 55% retained nipple sensitivity.
 

Unanswered Questions

In an accompanying article, Monica Morrow, MD, director of surgical breast oncology at the Memorial Sloan-Kettering Cancer Center in New York, acknowledged that the new evidence confirms the surgical approach’s feasibility but deems it insufficient to adopt it lightly. “At this point, the issue is not whether robotic mastectomy can be done but whether there is sufficient information about its oncologic safety that it should be done,” she wrote.

In a 2019 statement that was updated in 2021, the US Food and Drug Administration stated, “The safety and effectiveness of using robotically assisted surgical devices in mastectomy procedures or in the prevention or treatment of breast cancer have not been established.” The significance of this caution is underscored by the experience with laparoscopic and robotic radical hysterectomies. These procedures were widely adopted until a randomized prospective study demonstrated lower disease-free and overall survival for the minimally invasive approach compared with open surgery.

The University of Texas surgeons stated that acceptable safety and oncological outcomes for robotic NSM compared with conventional NSM had been demonstrated. They cited two trials with 238 cases and a median follow-up of less than 3 years. Dr. Morrow wrote, “While these reports provide reassurance that gross residual tumor is not being left behind, they do not address the issue of failure to remove all of the breast tissue due to thick skin flaps, with the potential for development of late recurrence or new cancers.” It is worth noting that even with the traditional surgical approach, the 5-year local recurrence rate after NSM is approximately double when observed with shorter follow-ups.

According to Dr. Morrow, the high rate of sensory preservation observed with robotic surgery, a desirable outcome for patients, is also a cause for concern. “While this may be due to incision placement or minimal skin flap retraction, as suggested by the authors, it is equally plausible that this could be due to thick skin flaps with preservation of the terminal branches of the fourth intercostal nerve.”

Therefore, more information on long-term oncological outcomes in a large number of patients will be necessary to confirm the safety of the procedure. In addition, measuring patient-reported outcomes will be useful in demonstrating that the benefits of the procedure outweigh increased operating times and costs. 

This article was translated from Univadis Italy, which is part of the Medscape Professional Network. A version of this article appeared on Medscape.com.

A study from the University of Texas demonstrates the feasibility of using robotic single-port laparoscopy in nipple-sparing mastectomy (NSM), a type of conservative mastectomy preserving the skin and nipple-areola complex. The new findings potentially expand the application of robotic surgery to a larger patient population but doubts about the safety of this approach linger.

Robotic Mastectomy

The first surgeries involving the Da Vinci robotic surgeon for breast removal date to 2015. Multiport robotic surgery faces significant obstacles in this field, however. Feasibility studies have primarily focused on women with small breasts, corresponding to cup size C or smaller.

In the study that was published in JAMA Surgery, surgeons used the more cost-effective single-port platform for bilateral NSM procedures. Among the 20 patients included in the analysis (age, 29-63 years), 11 underwent prophylactic mastectomy (for a high risk for cancer) and 9 had mastectomy for breast tumors. Breast sizes ranged from A cup to D cup.

The duration of the procedure, from skin incision to suture for both breasts, ranged from 205 to 351 minutes (median, 277 minutes). No immediate operative complications (eg, hematoma) occurred, and there was no need for conversion to open surgery in any case. Over the 36-month follow-up, there were no recurrences. About 95% of patients retained skin sensitivity and 55% retained nipple sensitivity.
 

Unanswered Questions

In an accompanying article, Monica Morrow, MD, director of surgical breast oncology at the Memorial Sloan-Kettering Cancer Center in New York, acknowledged that the new evidence confirms the surgical approach’s feasibility but deems it insufficient to adopt it lightly. “At this point, the issue is not whether robotic mastectomy can be done but whether there is sufficient information about its oncologic safety that it should be done,” she wrote.

In a 2019 statement that was updated in 2021, the US Food and Drug Administration stated, “The safety and effectiveness of using robotically assisted surgical devices in mastectomy procedures or in the prevention or treatment of breast cancer have not been established.” The significance of this caution is underscored by the experience with laparoscopic and robotic radical hysterectomies. These procedures were widely adopted until a randomized prospective study demonstrated lower disease-free and overall survival for the minimally invasive approach compared with open surgery.

The University of Texas surgeons stated that acceptable safety and oncological outcomes for robotic NSM compared with conventional NSM had been demonstrated. They cited two trials with 238 cases and a median follow-up of less than 3 years. Dr. Morrow wrote, “While these reports provide reassurance that gross residual tumor is not being left behind, they do not address the issue of failure to remove all of the breast tissue due to thick skin flaps, with the potential for development of late recurrence or new cancers.” It is worth noting that even with the traditional surgical approach, the 5-year local recurrence rate after NSM is approximately double when observed with shorter follow-ups.

According to Dr. Morrow, the high rate of sensory preservation observed with robotic surgery, a desirable outcome for patients, is also a cause for concern. “While this may be due to incision placement or minimal skin flap retraction, as suggested by the authors, it is equally plausible that this could be due to thick skin flaps with preservation of the terminal branches of the fourth intercostal nerve.”

Therefore, more information on long-term oncological outcomes in a large number of patients will be necessary to confirm the safety of the procedure. In addition, measuring patient-reported outcomes will be useful in demonstrating that the benefits of the procedure outweigh increased operating times and costs. 

This article was translated from Univadis Italy, which is part of the Medscape Professional Network. A version of this article appeared on Medscape.com.

A study from the University of Texas demonstrates the feasibility of using robotic single-port laparoscopy in nipple-sparing mastectomy (NSM), a type of conservative mastectomy preserving the skin and nipple-areola complex. The new findings potentially expand the application of robotic surgery to a larger patient population but doubts about the safety of this approach linger.

Robotic Mastectomy

The first surgeries involving the Da Vinci robotic surgeon for breast removal date to 2015. Multiport robotic surgery faces significant obstacles in this field, however. Feasibility studies have primarily focused on women with small breasts, corresponding to cup size C or smaller.

In the study that was published in JAMA Surgery, surgeons used the more cost-effective single-port platform for bilateral NSM procedures. Among the 20 patients included in the analysis (age, 29-63 years), 11 underwent prophylactic mastectomy (for a high risk for cancer) and 9 had mastectomy for breast tumors. Breast sizes ranged from A cup to D cup.

The duration of the procedure, from skin incision to suture for both breasts, ranged from 205 to 351 minutes (median, 277 minutes). No immediate operative complications (eg, hematoma) occurred, and there was no need for conversion to open surgery in any case. Over the 36-month follow-up, there were no recurrences. About 95% of patients retained skin sensitivity and 55% retained nipple sensitivity.
 

Unanswered Questions

In an accompanying article, Monica Morrow, MD, director of surgical breast oncology at the Memorial Sloan-Kettering Cancer Center in New York, acknowledged that the new evidence confirms the surgical approach’s feasibility but deems it insufficient to adopt it lightly. “At this point, the issue is not whether robotic mastectomy can be done but whether there is sufficient information about its oncologic safety that it should be done,” she wrote.

In a 2019 statement that was updated in 2021, the US Food and Drug Administration stated, “The safety and effectiveness of using robotically assisted surgical devices in mastectomy procedures or in the prevention or treatment of breast cancer have not been established.” The significance of this caution is underscored by the experience with laparoscopic and robotic radical hysterectomies. These procedures were widely adopted until a randomized prospective study demonstrated lower disease-free and overall survival for the minimally invasive approach compared with open surgery.

The University of Texas surgeons stated that acceptable safety and oncological outcomes for robotic NSM compared with conventional NSM had been demonstrated. They cited two trials with 238 cases and a median follow-up of less than 3 years. Dr. Morrow wrote, “While these reports provide reassurance that gross residual tumor is not being left behind, they do not address the issue of failure to remove all of the breast tissue due to thick skin flaps, with the potential for development of late recurrence or new cancers.” It is worth noting that even with the traditional surgical approach, the 5-year local recurrence rate after NSM is approximately double when observed with shorter follow-ups.

According to Dr. Morrow, the high rate of sensory preservation observed with robotic surgery, a desirable outcome for patients, is also a cause for concern. “While this may be due to incision placement or minimal skin flap retraction, as suggested by the authors, it is equally plausible that this could be due to thick skin flaps with preservation of the terminal branches of the fourth intercostal nerve.”

Therefore, more information on long-term oncological outcomes in a large number of patients will be necessary to confirm the safety of the procedure. In addition, measuring patient-reported outcomes will be useful in demonstrating that the benefits of the procedure outweigh increased operating times and costs. 

This article was translated from Univadis Italy, which is part of the Medscape Professional Network. A version of this article appeared on Medscape.com.

Exposure to even moderate concentrations of radon is associated with a significant increase in stroke risk, new research suggests.

An analysis of radon exposures in more than 150,000 postmenopausal women in the Women’s Health Initiative revealed a 14% higher stroke risk in those exposed to the highest concentrations compared with those exposed to the lowest concentrations. Even moderate concentrations of radon were associated with a 6% higher stroke risk.

Radon is the second leading cause of lung cancer, but little was known about how exposure to the gas might affect stroke risk in women. 

“Our research found an increased risk of stroke among participants exposed to radon above — and as many as 2 picocuries per liter (pCi/L) below — concentrations that usually trigger Environmental Protection Agency recommendations to install a home radon mitigation system,” senior author Eric A. Whitsel, MD, MPH, professor of epidemiology and medicine, University of North Carolina, Chapel Hill, said in a news release.

The study was published online on January 31, 2024, in Neurology.

Women Particularly Affected

Radon is a naturally occurring odorless radioactive gas produced when uranium or radium break down in rocks and soil. Its presence is increasing as a result of climate change, and it is increasingly being found in people’s homes. When inhaled, this air pollutant releases ionizing radiation in the lungs and is seen as second only to smoking as an established cause of lung cancer.

The National Radon Action Plan of the US Environmental Protection Agency (EPA) lays out testing and mitigation guidelines based on the known role of radon in lung carcinogenesis. But radon testing and mitigation are less common than recommended, and the EPA’s action plan doesn’t cover diseases other than lung cancer.

Compared with men, women have a higher rate of stroke and, in the US, typically spend about 11% more hours per day indoors at home, which investigators note highlights a “potential role of the residential environment among other risk factors specific to women.”

Researchers examined longitudinal associations between home radon exposure and incident stroke in 158,910 women at baseline (mean age 63.2 years; 83% White) over a mean follow-up of 13.4 years. During this time, participants experienced a total of 6979 strokes.

Participants’ home addresses were linked to radon concentration data drawn from the US Geological Survey and the EPA, which recommends that average indoor radon concentrations not exceed 4 pCi/L. 

The highest radon exposure group resided in areas where average radon concentrations were < 4 pCi/L; the middle exposure group lived in regions with average concentrations of 2-4 pCi/L; and the lowest exposure group lived in areas with average concentrations < 2 pCi/L. 

The researchers adjusted for demographic, social, behavioral, and clinical characteristics.

Public Health Implications

The incidence rates of stroke per 100,000 women in the lowest, middle, and highest radon concentration areas were 333, 343, and 349, respectively.

Stroke risk was 6% higher among those in the middle exposure group (adjusted hazard ratio [aHR], 1.06; 95% CI, 0.99-1.13) and 14% higher in the highest exposure group (aHR, 1.14; 95% CI, 1.05-1.22) compared with the lowest exposure group.

Notably, stroke risk was significant even at concentrations ranging from 2 to 4 pCi/L (P = .0004) vs < 2 pCi/L, which is below the EPA›s Radon Action Level for mitigation. 

The findings remained robust in sensitivity analyses, although the associations were slightly stronger for ischemic stroke (especially cardioembolic, small-vessel occlusive, and very large artery atherosclerotic) compared with hemorrhagic stroke.

“Radon is an indoor air pollutant that can only be detected through testing that measures concentrations of the gas in homes,” Dr. Whitsel said in the release. “More studies are needed to confirm our findings. Confirmation would present an opportunity to improve public health by addressing an emerging risk factor for stroke.”

The study lacked gender and racial/ethnic diversity, so the findings may not be generalizable to other populations. 

“Replication studies of individual-level radon exposures are needed to confirm this positive radon-stroke association,” the authors write. “Confirmation would present a potential opportunity to affect public health by addressing a pervasive environmental risk factor for stroke and thereby merit reconsideration of extant radon policy.”

The study was funded by the National Institute of Environmental Health Sciences and National Heart, Lung, and Blood Institute. Dr. Whitsel and coauthors report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Exposure to even moderate concentrations of radon is associated with a significant increase in stroke risk, new research suggests.

An analysis of radon exposures in more than 150,000 postmenopausal women in the Women’s Health Initiative revealed a 14% higher stroke risk in those exposed to the highest concentrations compared with those exposed to the lowest concentrations. Even moderate concentrations of radon were associated with a 6% higher stroke risk.

Radon is the second leading cause of lung cancer, but little was known about how exposure to the gas might affect stroke risk in women. 

“Our research found an increased risk of stroke among participants exposed to radon above — and as many as 2 picocuries per liter (pCi/L) below — concentrations that usually trigger Environmental Protection Agency recommendations to install a home radon mitigation system,” senior author Eric A. Whitsel, MD, MPH, professor of epidemiology and medicine, University of North Carolina, Chapel Hill, said in a news release.

The study was published online on January 31, 2024, in Neurology.

Women Particularly Affected

Radon is a naturally occurring odorless radioactive gas produced when uranium or radium break down in rocks and soil. Its presence is increasing as a result of climate change, and it is increasingly being found in people’s homes. When inhaled, this air pollutant releases ionizing radiation in the lungs and is seen as second only to smoking as an established cause of lung cancer.

The National Radon Action Plan of the US Environmental Protection Agency (EPA) lays out testing and mitigation guidelines based on the known role of radon in lung carcinogenesis. But radon testing and mitigation are less common than recommended, and the EPA’s action plan doesn’t cover diseases other than lung cancer.

Compared with men, women have a higher rate of stroke and, in the US, typically spend about 11% more hours per day indoors at home, which investigators note highlights a “potential role of the residential environment among other risk factors specific to women.”

Researchers examined longitudinal associations between home radon exposure and incident stroke in 158,910 women at baseline (mean age 63.2 years; 83% White) over a mean follow-up of 13.4 years. During this time, participants experienced a total of 6979 strokes.

Participants’ home addresses were linked to radon concentration data drawn from the US Geological Survey and the EPA, which recommends that average indoor radon concentrations not exceed 4 pCi/L. 

The highest radon exposure group resided in areas where average radon concentrations were < 4 pCi/L; the middle exposure group lived in regions with average concentrations of 2-4 pCi/L; and the lowest exposure group lived in areas with average concentrations < 2 pCi/L. 

The researchers adjusted for demographic, social, behavioral, and clinical characteristics.

Public Health Implications

The incidence rates of stroke per 100,000 women in the lowest, middle, and highest radon concentration areas were 333, 343, and 349, respectively.

Stroke risk was 6% higher among those in the middle exposure group (adjusted hazard ratio [aHR], 1.06; 95% CI, 0.99-1.13) and 14% higher in the highest exposure group (aHR, 1.14; 95% CI, 1.05-1.22) compared with the lowest exposure group.

Notably, stroke risk was significant even at concentrations ranging from 2 to 4 pCi/L (P = .0004) vs < 2 pCi/L, which is below the EPA›s Radon Action Level for mitigation. 

The findings remained robust in sensitivity analyses, although the associations were slightly stronger for ischemic stroke (especially cardioembolic, small-vessel occlusive, and very large artery atherosclerotic) compared with hemorrhagic stroke.

“Radon is an indoor air pollutant that can only be detected through testing that measures concentrations of the gas in homes,” Dr. Whitsel said in the release. “More studies are needed to confirm our findings. Confirmation would present an opportunity to improve public health by addressing an emerging risk factor for stroke.”

The study lacked gender and racial/ethnic diversity, so the findings may not be generalizable to other populations. 

“Replication studies of individual-level radon exposures are needed to confirm this positive radon-stroke association,” the authors write. “Confirmation would present a potential opportunity to affect public health by addressing a pervasive environmental risk factor for stroke and thereby merit reconsideration of extant radon policy.”

The study was funded by the National Institute of Environmental Health Sciences and National Heart, Lung, and Blood Institute. Dr. Whitsel and coauthors report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Exposure to even moderate concentrations of radon is associated with a significant increase in stroke risk, new research suggests.

An analysis of radon exposures in more than 150,000 postmenopausal women in the Women’s Health Initiative revealed a 14% higher stroke risk in those exposed to the highest concentrations compared with those exposed to the lowest concentrations. Even moderate concentrations of radon were associated with a 6% higher stroke risk.

Radon is the second leading cause of lung cancer, but little was known about how exposure to the gas might affect stroke risk in women. 

“Our research found an increased risk of stroke among participants exposed to radon above — and as many as 2 picocuries per liter (pCi/L) below — concentrations that usually trigger Environmental Protection Agency recommendations to install a home radon mitigation system,” senior author Eric A. Whitsel, MD, MPH, professor of epidemiology and medicine, University of North Carolina, Chapel Hill, said in a news release.

The study was published online on January 31, 2024, in Neurology.

Women Particularly Affected

Radon is a naturally occurring odorless radioactive gas produced when uranium or radium break down in rocks and soil. Its presence is increasing as a result of climate change, and it is increasingly being found in people’s homes. When inhaled, this air pollutant releases ionizing radiation in the lungs and is seen as second only to smoking as an established cause of lung cancer.

The National Radon Action Plan of the US Environmental Protection Agency (EPA) lays out testing and mitigation guidelines based on the known role of radon in lung carcinogenesis. But radon testing and mitigation are less common than recommended, and the EPA’s action plan doesn’t cover diseases other than lung cancer.

Compared with men, women have a higher rate of stroke and, in the US, typically spend about 11% more hours per day indoors at home, which investigators note highlights a “potential role of the residential environment among other risk factors specific to women.”

Researchers examined longitudinal associations between home radon exposure and incident stroke in 158,910 women at baseline (mean age 63.2 years; 83% White) over a mean follow-up of 13.4 years. During this time, participants experienced a total of 6979 strokes.

Participants’ home addresses were linked to radon concentration data drawn from the US Geological Survey and the EPA, which recommends that average indoor radon concentrations not exceed 4 pCi/L. 

The highest radon exposure group resided in areas where average radon concentrations were < 4 pCi/L; the middle exposure group lived in regions with average concentrations of 2-4 pCi/L; and the lowest exposure group lived in areas with average concentrations < 2 pCi/L. 

The researchers adjusted for demographic, social, behavioral, and clinical characteristics.

Public Health Implications

The incidence rates of stroke per 100,000 women in the lowest, middle, and highest radon concentration areas were 333, 343, and 349, respectively.

Stroke risk was 6% higher among those in the middle exposure group (adjusted hazard ratio [aHR], 1.06; 95% CI, 0.99-1.13) and 14% higher in the highest exposure group (aHR, 1.14; 95% CI, 1.05-1.22) compared with the lowest exposure group.

Notably, stroke risk was significant even at concentrations ranging from 2 to 4 pCi/L (P = .0004) vs < 2 pCi/L, which is below the EPA›s Radon Action Level for mitigation. 

The findings remained robust in sensitivity analyses, although the associations were slightly stronger for ischemic stroke (especially cardioembolic, small-vessel occlusive, and very large artery atherosclerotic) compared with hemorrhagic stroke.

“Radon is an indoor air pollutant that can only be detected through testing that measures concentrations of the gas in homes,” Dr. Whitsel said in the release. “More studies are needed to confirm our findings. Confirmation would present an opportunity to improve public health by addressing an emerging risk factor for stroke.”

The study lacked gender and racial/ethnic diversity, so the findings may not be generalizable to other populations. 

“Replication studies of individual-level radon exposures are needed to confirm this positive radon-stroke association,” the authors write. “Confirmation would present a potential opportunity to affect public health by addressing a pervasive environmental risk factor for stroke and thereby merit reconsideration of extant radon policy.”

The study was funded by the National Institute of Environmental Health Sciences and National Heart, Lung, and Blood Institute. Dr. Whitsel and coauthors report no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Tumor regrowth predicts distant metastases in patients with rectal cancer undergoing surveillance after complete clinical responses to neoadjuvant therapy.

METHODOLOGY:

• “Watch and wait” is generally offered to patients with rectal cancer who have a complete clinical response to neoadjuvant therapy.
• Up to 30% of tumors regrow within 3 years, and about 5% of patients develop distant metastases.
• To get a better handle on the risk factors, investigators identified 508 watch-and-wait patients from the International Watch & Wait database who had a local regrowth and underwent resection.
• The team compared them with 893 patients from a Spanish registry who had total mesorectal excisions after neoadjuvant therapy and who were found to have had a nearly complete response to neoadjuvant therapy, meaning that 90% or more of their tumor was gone.

TAKEAWAY:

• Three-year distant metastasis–free survival was 75% in the watch-and-wait/regrowth group vs 87% in the upfront surgery arm (P = .001); the results held when the two groups were stratified by pathological T stage and nodal status.
• Patients with local regrowth also had a higher risk of developing distant metastasis (22.8% vs 10.2% at 3 years).
• Local regrowth was an independent risk factor for distant metastasis, along with higher pathological T stage and positive nodal status on the resected regrowth specimen.
• Baseline clinical T stage and nodal status were not significantly associated with risk.

IN PRACTICE:

“Leaving the primary undetectable tumor in situ until development of local regrowth may result in worse oncological outcomes ... Efforts should be made to minimize the risk of local regrowth among patients undergoing watch and wait by the use of very stringent criteria for the identification of a clinical complete response.” There may be a role for ctDNA to improve patient selection for watch and wait.

SOURCE:

The study was led by Laura Melina Fernandez of the Champalimaud Foundation in Lisbon, Portugal, and presented on January 20, 2024, at the ASCO Gastrointestinal Cancers Symposium.

LIMITATIONS:

The definition of “complete clinical response” and selection of patients for watch and wait varied across International Watch & Wait database institutions. Recruitment occurred before implementation of total neoadjuvant therapy regimens.

DISCLOSURES:

There was no external funding for the work. The lead investigator didn’t have any disclosures.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Tumor regrowth predicts distant metastases in patients with rectal cancer undergoing surveillance after complete clinical responses to neoadjuvant therapy.

METHODOLOGY:

• “Watch and wait” is generally offered to patients with rectal cancer who have a complete clinical response to neoadjuvant therapy.
• Up to 30% of tumors regrow within 3 years, and about 5% of patients develop distant metastases.
• To get a better handle on the risk factors, investigators identified 508 watch-and-wait patients from the International Watch & Wait database who had a local regrowth and underwent resection.
• The team compared them with 893 patients from a Spanish registry who had total mesorectal excisions after neoadjuvant therapy and who were found to have had a nearly complete response to neoadjuvant therapy, meaning that 90% or more of their tumor was gone.

TAKEAWAY:

• Three-year distant metastasis–free survival was 75% in the watch-and-wait/regrowth group vs 87% in the upfront surgery arm (P = .001); the results held when the two groups were stratified by pathological T stage and nodal status.
• Patients with local regrowth also had a higher risk of developing distant metastasis (22.8% vs 10.2% at 3 years).
• Local regrowth was an independent risk factor for distant metastasis, along with higher pathological T stage and positive nodal status on the resected regrowth specimen.
• Baseline clinical T stage and nodal status were not significantly associated with risk.

IN PRACTICE:

“Leaving the primary undetectable tumor in situ until development of local regrowth may result in worse oncological outcomes ... Efforts should be made to minimize the risk of local regrowth among patients undergoing watch and wait by the use of very stringent criteria for the identification of a clinical complete response.” There may be a role for ctDNA to improve patient selection for watch and wait.

SOURCE:

The study was led by Laura Melina Fernandez of the Champalimaud Foundation in Lisbon, Portugal, and presented on January 20, 2024, at the ASCO Gastrointestinal Cancers Symposium.

LIMITATIONS:

The definition of “complete clinical response” and selection of patients for watch and wait varied across International Watch & Wait database institutions. Recruitment occurred before implementation of total neoadjuvant therapy regimens.

DISCLOSURES:

There was no external funding for the work. The lead investigator didn’t have any disclosures.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Tumor regrowth predicts distant metastases in patients with rectal cancer undergoing surveillance after complete clinical responses to neoadjuvant therapy.

METHODOLOGY:

• “Watch and wait” is generally offered to patients with rectal cancer who have a complete clinical response to neoadjuvant therapy.
• Up to 30% of tumors regrow within 3 years, and about 5% of patients develop distant metastases.
• To get a better handle on the risk factors, investigators identified 508 watch-and-wait patients from the International Watch & Wait database who had a local regrowth and underwent resection.
• The team compared them with 893 patients from a Spanish registry who had total mesorectal excisions after neoadjuvant therapy and who were found to have had a nearly complete response to neoadjuvant therapy, meaning that 90% or more of their tumor was gone.

TAKEAWAY:

• Three-year distant metastasis–free survival was 75% in the watch-and-wait/regrowth group vs 87% in the upfront surgery arm (P = .001); the results held when the two groups were stratified by pathological T stage and nodal status.
• Patients with local regrowth also had a higher risk of developing distant metastasis (22.8% vs 10.2% at 3 years).
• Local regrowth was an independent risk factor for distant metastasis, along with higher pathological T stage and positive nodal status on the resected regrowth specimen.
• Baseline clinical T stage and nodal status were not significantly associated with risk.

IN PRACTICE:

“Leaving the primary undetectable tumor in situ until development of local regrowth may result in worse oncological outcomes ... Efforts should be made to minimize the risk of local regrowth among patients undergoing watch and wait by the use of very stringent criteria for the identification of a clinical complete response.” There may be a role for ctDNA to improve patient selection for watch and wait.

SOURCE:

The study was led by Laura Melina Fernandez of the Champalimaud Foundation in Lisbon, Portugal, and presented on January 20, 2024, at the ASCO Gastrointestinal Cancers Symposium.

LIMITATIONS:

The definition of “complete clinical response” and selection of patients for watch and wait varied across International Watch & Wait database institutions. Recruitment occurred before implementation of total neoadjuvant therapy regimens.

DISCLOSURES:

There was no external funding for the work. The lead investigator didn’t have any disclosures.
 

A version of this article appeared on Medscape.com.

Healthcare workers have been at an increased risk for SARS-CoV-2 infection and mental distress such as anxiety and depression during the pandemic, according to new research.

In an analysis of administrative health records for about 3000 healthcare workers in Alberta, Canada, the workers were as much as twice as likely to become infected with SARS-CoV-2 compared with the overall population. The risk for infection was higher among healthcare workers in the first two waves of the pandemic and again during the fifth wave.

“Previous publications, including ours, suggested that the main problem was in the early weeks and months of the pandemic, but this paper shows that it continued until the later stages,” senior author Nicola Cherry, MD, an occupational epidemiologist at the University of Alberta in Edmonton, Canada, told this news organization.

The findings were published in the Canadian Journal of Public Health.
 

Wave Upon Wave

In the current study, the investigators sought to compare the risk for SARS-CoV-2 infection and mental distress among healthcare workers and among community referents (CRs). They examined the following waves of the COVID-19 pandemic:

• Wave 1: From March to June 2020 (4 months).
• Wave 2: From July 2020 to February 2021 (8 months).
• Wave 3: From March to June 2021 (4 months).
• Wave 4: From July to October 2021 (4 months).
• Wave 5 (Omicron): From November 2021 to March 2022 (5 months).

Healthcare workers in Alberta were asked at recruitment for consent to match their individual records to the Alberta Administrative Health Database. As the pandemic progressed, participants were also asked for consent to be linked to COVID-19 immunization records maintained by the provinces, as well as for the results of all polymerase chain reaction (PCR) testing for the SARS-CoV-2 virus.

The investigators matched 2959 healthcare workers to 14,546 CRs according to their age, sex, geographic location in Alberta, and number of physician claims from April 1, 2019, to March 31, 2020.

Incident SARS-CoV-2 infection was examined using PCR testing and the first date of a physician consultation at which the code for SARS-CoV-2 infection had been recorded. Mental health disorders were identified from physician records. They included anxiety disorders, stress and adjustment reactions, and depressive disorders.

Most (79.5%) of the healthcare workers were registered nurses, followed by physicians (16.1%), healthcare aides (2.4%), and licensed practical nurses (2.0%). Most participants (87.5%) were female. The median age at recruitment was 44 years.

Healthcare workers were at a greater risk for COVID-19 overall, with the first SARS-CoV-2 infection defined from either PCR tests (odds ratio [OR], 1.96) or from physician records (OR, 1.33). They were also at an increased risk for anxiety (adjusted OR, 1.25; P < .001), stress/adjustment reaction (adjusted OR, 1.52; P < .001), and depressive condition (adjusted OR, 1.39; P < .001). Moreover, the excess risks for stress/adjustment reactions and depressive conditions increased with successive waves during the pandemic, peaking in the fourth wave and continuing in the fifth wave.

“Although the increase was less in the middle of the phases of the pandemic, it came back with a vengeance during the last phase, which was the Omicron phase,” said Dr. Cherry.

“Employers of healthcare workers can’t assume that everything is now under control, that they know what they’re doing, and that there is no risk. We are now having some increases in COVID. It’s going to go on. The pandemic is not over in that sense, and infection control continues to be major,” she added.

The finding that mental health worsened among healthcare workers was not surprising, Dr. Cherry said. Even before the pandemic, studies had shown that healthcare workers were at a greater risk for depression than the population overall.

“There is a lot of need for care in mental health support of healthcare workers, whether during a pandemic or not,” said Dr. Cherry.
 

Nurses Are Suffering

Commenting on the research for this news organization, Farinaz Havaei, PhD, RN, assistant professor of nursing at the University of British Columbia in Vancouver, Canada, said, “This is a very important and timely study that draws on objective clinical and administrative data, as opposed to healthcare workers’ subjective reports.” Dr. Havaei did not participate in the research.

Overall, the findings are consistent with previous research that drew upon healthcare workers’ reports. They speak to the chronic and cumulative impact of COVID-19 and its associated stressors on the mental health and well-being of healthcare workers, said Dr. Havaei.

“The likelihood of stress/adjustment reaction and depression showed a relatively steady increase with increasing COVID-19 waves. This increase can likely be explained by healthcare workers’ depleting emotional reserves for coping with chronic workplace stressors such as concerns about exposure to COVID-19, inadequate staffing, and work overload,” she said. Witnessing the suffering and trauma of patients and their families likely added to this risk.

Dr. Havaei also pointed out that most of the study participants were nurses. The findings are consistent with prepandemic research that showed that the suboptimal conditions that nurses increasingly faced resulted in high levels of exhaustion and burnout.

“While I agree with the authors’ call for more mental health support for healthcare workers, I think prevention efforts that address the root cause of the problem should be prioritized,” she said.
 

From Heroes to Zeros

The same phenomena have been observed in the United States, said John Q. Young, MD, MPP, PhD, professor and chair of psychiatry at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York. In various studies, Dr. Young and his colleagues have reported a strong association between exposure to the stressors of the pandemic and subsequent development of depression, anxiety, and posttraumatic stress disorder (PTSD) among healthcare workers.

“The findings from Alberta are remarkably consistent. In the beginning of the pandemic, there was a lot of acknowledgment of the work healthcare workers were doing. The fire department clapping as you leave work at night, being called heroes, even though a lot of healthcare workers feel uncomfortable with the hero language because they don’t feel like heroes. Yes, they’re afraid, but they are going to do what they need to do and help,” he said.

But as the pandemic continued, public sentiment changed, Dr. Young said. “They’ve gone from heroes to zeros. Now we are seeing the accumulated, chronic effects over months and years, and these are significant. Our healthcare workforce is vulnerable now. The reserves are low. There are serious shortages in nursing, with more retirements and more people leaving the field,” he said.

As part of a campaign to help healthcare workers cope, psychiatrists at Northwell Health have started a program called Stress First Aid at their Center for Traumatic Stress Response Resilience, where they train nurses, physicians, and other healthcare staff to use basic tools to recognize and respond to stress and distress in themselves and in their colleagues, said Dr. Young.

“For those healthcare workers who find that they are struggling and need more support, there is resilience coaching, which is one-on-one support. For those who need more clinical attention, there is a clinical program where our healthcare workers can meet with a psychologist, psychiatrist, or a therapist, to work through depression, PTSD, and anxiety. We didn’t have this before the pandemic, but it is now a big focus for our workforce,” he said. “We are trying to build resilience. The trauma is real.”

The study was supported by the College of Physicians and Surgeons of Alberta, the Canadian Institutes of Health Research, and the Canadian Immunology Task Force. Dr. Cherry and Dr. Havaei reported no relevant financial relationships. Dr. Young reported that he is senior vice president of behavioral health at Northwell.

A version of this article appeared on Medscape.com.

Healthcare workers have been at an increased risk for SARS-CoV-2 infection and mental distress such as anxiety and depression during the pandemic, according to new research.

In an analysis of administrative health records for about 3000 healthcare workers in Alberta, Canada, the workers were as much as twice as likely to become infected with SARS-CoV-2 compared with the overall population. The risk for infection was higher among healthcare workers in the first two waves of the pandemic and again during the fifth wave.

“Previous publications, including ours, suggested that the main problem was in the early weeks and months of the pandemic, but this paper shows that it continued until the later stages,” senior author Nicola Cherry, MD, an occupational epidemiologist at the University of Alberta in Edmonton, Canada, told this news organization.

The findings were published in the Canadian Journal of Public Health.
 

Wave Upon Wave

In the current study, the investigators sought to compare the risk for SARS-CoV-2 infection and mental distress among healthcare workers and among community referents (CRs). They examined the following waves of the COVID-19 pandemic:

• Wave 1: From March to June 2020 (4 months).
• Wave 2: From July 2020 to February 2021 (8 months).
• Wave 3: From March to June 2021 (4 months).
• Wave 4: From July to October 2021 (4 months).
• Wave 5 (Omicron): From November 2021 to March 2022 (5 months).

Healthcare workers in Alberta were asked at recruitment for consent to match their individual records to the Alberta Administrative Health Database. As the pandemic progressed, participants were also asked for consent to be linked to COVID-19 immunization records maintained by the provinces, as well as for the results of all polymerase chain reaction (PCR) testing for the SARS-CoV-2 virus.

The investigators matched 2959 healthcare workers to 14,546 CRs according to their age, sex, geographic location in Alberta, and number of physician claims from April 1, 2019, to March 31, 2020.

Incident SARS-CoV-2 infection was examined using PCR testing and the first date of a physician consultation at which the code for SARS-CoV-2 infection had been recorded. Mental health disorders were identified from physician records. They included anxiety disorders, stress and adjustment reactions, and depressive disorders.

Most (79.5%) of the healthcare workers were registered nurses, followed by physicians (16.1%), healthcare aides (2.4%), and licensed practical nurses (2.0%). Most participants (87.5%) were female. The median age at recruitment was 44 years.

Healthcare workers were at a greater risk for COVID-19 overall, with the first SARS-CoV-2 infection defined from either PCR tests (odds ratio [OR], 1.96) or from physician records (OR, 1.33). They were also at an increased risk for anxiety (adjusted OR, 1.25; P < .001), stress/adjustment reaction (adjusted OR, 1.52; P < .001), and depressive condition (adjusted OR, 1.39; P < .001). Moreover, the excess risks for stress/adjustment reactions and depressive conditions increased with successive waves during the pandemic, peaking in the fourth wave and continuing in the fifth wave.

“Although the increase was less in the middle of the phases of the pandemic, it came back with a vengeance during the last phase, which was the Omicron phase,” said Dr. Cherry.

“Employers of healthcare workers can’t assume that everything is now under control, that they know what they’re doing, and that there is no risk. We are now having some increases in COVID. It’s going to go on. The pandemic is not over in that sense, and infection control continues to be major,” she added.

The finding that mental health worsened among healthcare workers was not surprising, Dr. Cherry said. Even before the pandemic, studies had shown that healthcare workers were at a greater risk for depression than the population overall.

“There is a lot of need for care in mental health support of healthcare workers, whether during a pandemic or not,” said Dr. Cherry.
 

Nurses Are Suffering

Commenting on the research for this news organization, Farinaz Havaei, PhD, RN, assistant professor of nursing at the University of British Columbia in Vancouver, Canada, said, “This is a very important and timely study that draws on objective clinical and administrative data, as opposed to healthcare workers’ subjective reports.” Dr. Havaei did not participate in the research.

Overall, the findings are consistent with previous research that drew upon healthcare workers’ reports. They speak to the chronic and cumulative impact of COVID-19 and its associated stressors on the mental health and well-being of healthcare workers, said Dr. Havaei.

“The likelihood of stress/adjustment reaction and depression showed a relatively steady increase with increasing COVID-19 waves. This increase can likely be explained by healthcare workers’ depleting emotional reserves for coping with chronic workplace stressors such as concerns about exposure to COVID-19, inadequate staffing, and work overload,” she said. Witnessing the suffering and trauma of patients and their families likely added to this risk.

Dr. Havaei also pointed out that most of the study participants were nurses. The findings are consistent with prepandemic research that showed that the suboptimal conditions that nurses increasingly faced resulted in high levels of exhaustion and burnout.

“While I agree with the authors’ call for more mental health support for healthcare workers, I think prevention efforts that address the root cause of the problem should be prioritized,” she said.
 

From Heroes to Zeros

The same phenomena have been observed in the United States, said John Q. Young, MD, MPP, PhD, professor and chair of psychiatry at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York. In various studies, Dr. Young and his colleagues have reported a strong association between exposure to the stressors of the pandemic and subsequent development of depression, anxiety, and posttraumatic stress disorder (PTSD) among healthcare workers.

“The findings from Alberta are remarkably consistent. In the beginning of the pandemic, there was a lot of acknowledgment of the work healthcare workers were doing. The fire department clapping as you leave work at night, being called heroes, even though a lot of healthcare workers feel uncomfortable with the hero language because they don’t feel like heroes. Yes, they’re afraid, but they are going to do what they need to do and help,” he said.

But as the pandemic continued, public sentiment changed, Dr. Young said. “They’ve gone from heroes to zeros. Now we are seeing the accumulated, chronic effects over months and years, and these are significant. Our healthcare workforce is vulnerable now. The reserves are low. There are serious shortages in nursing, with more retirements and more people leaving the field,” he said.

As part of a campaign to help healthcare workers cope, psychiatrists at Northwell Health have started a program called Stress First Aid at their Center for Traumatic Stress Response Resilience, where they train nurses, physicians, and other healthcare staff to use basic tools to recognize and respond to stress and distress in themselves and in their colleagues, said Dr. Young.

“For those healthcare workers who find that they are struggling and need more support, there is resilience coaching, which is one-on-one support. For those who need more clinical attention, there is a clinical program where our healthcare workers can meet with a psychologist, psychiatrist, or a therapist, to work through depression, PTSD, and anxiety. We didn’t have this before the pandemic, but it is now a big focus for our workforce,” he said. “We are trying to build resilience. The trauma is real.”

The study was supported by the College of Physicians and Surgeons of Alberta, the Canadian Institutes of Health Research, and the Canadian Immunology Task Force. Dr. Cherry and Dr. Havaei reported no relevant financial relationships. Dr. Young reported that he is senior vice president of behavioral health at Northwell.

A version of this article appeared on Medscape.com.

Healthcare workers have been at an increased risk for SARS-CoV-2 infection and mental distress such as anxiety and depression during the pandemic, according to new research.

In an analysis of administrative health records for about 3000 healthcare workers in Alberta, Canada, the workers were as much as twice as likely to become infected with SARS-CoV-2 compared with the overall population. The risk for infection was higher among healthcare workers in the first two waves of the pandemic and again during the fifth wave.

“Previous publications, including ours, suggested that the main problem was in the early weeks and months of the pandemic, but this paper shows that it continued until the later stages,” senior author Nicola Cherry, MD, an occupational epidemiologist at the University of Alberta in Edmonton, Canada, told this news organization.

The findings were published in the Canadian Journal of Public Health.
 

Wave Upon Wave

In the current study, the investigators sought to compare the risk for SARS-CoV-2 infection and mental distress among healthcare workers and among community referents (CRs). They examined the following waves of the COVID-19 pandemic:

• Wave 1: From March to June 2020 (4 months).
• Wave 2: From July 2020 to February 2021 (8 months).
• Wave 3: From March to June 2021 (4 months).
• Wave 4: From July to October 2021 (4 months).
• Wave 5 (Omicron): From November 2021 to March 2022 (5 months).

Healthcare workers in Alberta were asked at recruitment for consent to match their individual records to the Alberta Administrative Health Database. As the pandemic progressed, participants were also asked for consent to be linked to COVID-19 immunization records maintained by the provinces, as well as for the results of all polymerase chain reaction (PCR) testing for the SARS-CoV-2 virus.

The investigators matched 2959 healthcare workers to 14,546 CRs according to their age, sex, geographic location in Alberta, and number of physician claims from April 1, 2019, to March 31, 2020.

Incident SARS-CoV-2 infection was examined using PCR testing and the first date of a physician consultation at which the code for SARS-CoV-2 infection had been recorded. Mental health disorders were identified from physician records. They included anxiety disorders, stress and adjustment reactions, and depressive disorders.

Most (79.5%) of the healthcare workers were registered nurses, followed by physicians (16.1%), healthcare aides (2.4%), and licensed practical nurses (2.0%). Most participants (87.5%) were female. The median age at recruitment was 44 years.

Healthcare workers were at a greater risk for COVID-19 overall, with the first SARS-CoV-2 infection defined from either PCR tests (odds ratio [OR], 1.96) or from physician records (OR, 1.33). They were also at an increased risk for anxiety (adjusted OR, 1.25; P < .001), stress/adjustment reaction (adjusted OR, 1.52; P < .001), and depressive condition (adjusted OR, 1.39; P < .001). Moreover, the excess risks for stress/adjustment reactions and depressive conditions increased with successive waves during the pandemic, peaking in the fourth wave and continuing in the fifth wave.

“Although the increase was less in the middle of the phases of the pandemic, it came back with a vengeance during the last phase, which was the Omicron phase,” said Dr. Cherry.

“Employers of healthcare workers can’t assume that everything is now under control, that they know what they’re doing, and that there is no risk. We are now having some increases in COVID. It’s going to go on. The pandemic is not over in that sense, and infection control continues to be major,” she added.

The finding that mental health worsened among healthcare workers was not surprising, Dr. Cherry said. Even before the pandemic, studies had shown that healthcare workers were at a greater risk for depression than the population overall.

“There is a lot of need for care in mental health support of healthcare workers, whether during a pandemic or not,” said Dr. Cherry.
 

Nurses Are Suffering

Commenting on the research for this news organization, Farinaz Havaei, PhD, RN, assistant professor of nursing at the University of British Columbia in Vancouver, Canada, said, “This is a very important and timely study that draws on objective clinical and administrative data, as opposed to healthcare workers’ subjective reports.” Dr. Havaei did not participate in the research.

Overall, the findings are consistent with previous research that drew upon healthcare workers’ reports. They speak to the chronic and cumulative impact of COVID-19 and its associated stressors on the mental health and well-being of healthcare workers, said Dr. Havaei.

“The likelihood of stress/adjustment reaction and depression showed a relatively steady increase with increasing COVID-19 waves. This increase can likely be explained by healthcare workers’ depleting emotional reserves for coping with chronic workplace stressors such as concerns about exposure to COVID-19, inadequate staffing, and work overload,” she said. Witnessing the suffering and trauma of patients and their families likely added to this risk.

Dr. Havaei also pointed out that most of the study participants were nurses. The findings are consistent with prepandemic research that showed that the suboptimal conditions that nurses increasingly faced resulted in high levels of exhaustion and burnout.

“While I agree with the authors’ call for more mental health support for healthcare workers, I think prevention efforts that address the root cause of the problem should be prioritized,” she said.
 

From Heroes to Zeros

The same phenomena have been observed in the United States, said John Q. Young, MD, MPP, PhD, professor and chair of psychiatry at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York. In various studies, Dr. Young and his colleagues have reported a strong association between exposure to the stressors of the pandemic and subsequent development of depression, anxiety, and posttraumatic stress disorder (PTSD) among healthcare workers.

“The findings from Alberta are remarkably consistent. In the beginning of the pandemic, there was a lot of acknowledgment of the work healthcare workers were doing. The fire department clapping as you leave work at night, being called heroes, even though a lot of healthcare workers feel uncomfortable with the hero language because they don’t feel like heroes. Yes, they’re afraid, but they are going to do what they need to do and help,” he said.

But as the pandemic continued, public sentiment changed, Dr. Young said. “They’ve gone from heroes to zeros. Now we are seeing the accumulated, chronic effects over months and years, and these are significant. Our healthcare workforce is vulnerable now. The reserves are low. There are serious shortages in nursing, with more retirements and more people leaving the field,” he said.

As part of a campaign to help healthcare workers cope, psychiatrists at Northwell Health have started a program called Stress First Aid at their Center for Traumatic Stress Response Resilience, where they train nurses, physicians, and other healthcare staff to use basic tools to recognize and respond to stress and distress in themselves and in their colleagues, said Dr. Young.

“For those healthcare workers who find that they are struggling and need more support, there is resilience coaching, which is one-on-one support. For those who need more clinical attention, there is a clinical program where our healthcare workers can meet with a psychologist, psychiatrist, or a therapist, to work through depression, PTSD, and anxiety. We didn’t have this before the pandemic, but it is now a big focus for our workforce,” he said. “We are trying to build resilience. The trauma is real.”

The study was supported by the College of Physicians and Surgeons of Alberta, the Canadian Institutes of Health Research, and the Canadian Immunology Task Force. Dr. Cherry and Dr. Havaei reported no relevant financial relationships. Dr. Young reported that he is senior vice president of behavioral health at Northwell.

A version of this article appeared on Medscape.com.

“Measles should be a memory, not a present risk,” Quique Bassat, MBBS, PhD, director general of the Barcelona Institute of Global Health, told this news organization.

That is certainly not the case right now in some parts of Europe. The World Health Organization (WHO) says the European Region is experiencing an alarming rise in cases, and urgent action is needed. Healthcare professionals are trying to gain control over measles outbreaks and roll out vaccination catch-up campaigns.

“What we are seeing currently is an almost 45-fold rise in measles cases in the WHO European Region,” Siddhartha Datta, MD, European regional advisor on vaccine-preventable diseases and immunization for the WHO, told this news organization. “In 2022, there were 940 cases, and in 2023 till November, it was around 42,000 plus. Between 2020 and 2022, we have seen 1.8 million children who have missed their measles vaccine doses.”
 

Lapses in Vaccinations

The overriding reason for the resurgence of measles is a backslide in vaccination coverage during the COVID-19 pandemic.

“During the COVID pandemic, we had a 5% decrease in coverage for most of the vaccines, and we are still seeing the consequences,” explained Dr. Bassat. “Measles is the perfect example of when you have a small drop of coverage you get outbreaks, as it’s extremely infectious and complicated to control.”

Reported national coverage with the first dose of measles-containing vaccine in the European Region fell from 96% in 2019 to 93% in 2022. Second-dose coverage fell from 92% in 2019 to 91% in 2022.

“You need to have 95% of the population vaccinated if you want herd immunity,” Dr. Bassat said.
 

Variation Across Europe

The WHO European Region comprises 53 countries, including Russia and some countries in central Asia. Its figures show Kazakhstan had the most recorded cases of measles last year, at more than 13,000, followed by the Russian Federation.

Romania declared a national epidemic in December 2023. Dr. Datta said there have also been outbreaks in Austria and France.

The UK Health Security Agency declared a major incident in January 2024 because of a surge in cases. From October 2023 to January 2024, there were 347 lab-confirmed cases of measles in England, with 127 of these confirmed in January. The West Midlands is an area of particular concern.

“It was not as though everything was rosy before COVID,” said Dr. Datta. “We saw wide variation in the coverage rates before the pandemic. Some countries weren’t doing as well. More particularly between some communities or municipalities, there were wide variations, and COVID-19 exacerbated the inequities in coverage. What we are seeing now is a combination of gaps before and after the pandemic, so it’s a compound problem.”

Belgium has also seen a measles resurgence, but not as many cases as the year before the pandemic. Laura Cornelissen, MD, works at the Belgian Public Health Institute, Sciensano, where she leads a team working on vaccine-preventable diseases.

She told this news organization: “We did observe a significant rise in cases and several clusters in 2023, compared to the very low numbers that were observed during the COVID-19 years. Preliminary figures indicate 85 measles cases for Belgium in 2023, leading to at least 26 hospitalizations. This is compared with eight cases for 2022, seven in 2021, and 47 in 2020; but 480 cases in the pre-pandemic year 2019.”

Sabrina Bacci, MD, head of vaccine-preventable diseases and immunization at the European Centre of Disease Control, told this news organization: “There have been a high number of cases in Romania and smaller outbreaks in other countries. However, there are a number of European countries which haven’t seen measles. Even though we have this variation between the different European countries, the tools to respond to outbreaks are the same.”
 

Vaccine Hesitance

Vaccine hesitance or even refusal is on the rise in Europe and elsewhere in the world.

“We can see from behavioral insights that, during COVID, people’s trust on vaccines, healthcare systems, and the government in general has gone down,” said Dr. Datta. “There had been skepticism before about the MMR jab causing autism, which was proved wrong, but vaccine skepticism shown throughout COVID is now showing its head in routine vaccine systems.”

The rise of so-called anti-vaxxers and associated fake conspiracy theories, including a mistrust of Big Pharma, hasn’t been helpful for encouraging essential childhood vaccination uptake, like measles, mumps, and rubella (MMR).

But the MMR vaccine backslide does not only originate in the pandemic.

Vanessa Saliba, consultant epidemiologist at the UK Health Security Agency, said: “MMR vaccine coverage has been falling for the last decade, with 1 out of 10 children starting school in England not protected.”

It could be that some people have religious concerns about the use of pork gelatin as a stabilizer in MMR vaccines. An alternative vaccine that does not contain pork gelatin can be requested.

Doctors and others in healthcare have a pivotal role to play when it comes to getting on top of the surges and educating patients, according to Dr. Bacci. “Healthcare professionals are the most precious resource we have, as they are the ones on the frontline explaining the importance of vaccination to their patients. It’s a very important dialogue.”
 

Clinics and Catch-Up Campaigns

Intensified routine immunization clinics and catch-up campaigns have been established in countries across Europe where they are needed.

Countries with large outbreaks are carrying out case investigations, identifying and vaccinating susceptible contacts, and generally raising awareness and implementing outbreak response immunization.

“Countries are really making good efforts and are systematically catching up the children who have missed their doses in the last 2 years. But the recovery to the 2019 levels has been slow, and more efforts and energy [need] to be put into this. We understand healthcare systems are stretched out from COVID, but this is not the time to lower our guard,” Dr. Datta said.

“Some countries are more proactive than others,” added Dr. Bassat. “Measles is an example of a disease where you typically organize catch-up campaigns. Measles has one of the highest reproductive numbers, as in the absence of preventive measures one infected person infects 14-16 others.”

All countries, even if they haven’t yet experienced measles outbreaks, are being urged by European healthcare authorities to look at potential immunity gaps and address them immediately.
 

When Will It Get Back to Normal?

“Measles was a disease that was targeted for elimination, but because of these outbreaks, we are seeing it almost everywhere again. We need to be careful and get on top of this,” warned Dr. Bassat.

Dr. Datta said it’s up to member states, decision-makers, healthcare leaders, and parents to come together to raise the immunity profiles of the European population. “Vaccination is a shared responsibility. The tools are effective. We just need to be ahead of the virus, and that is the challenge.”

Dr. Bacci added, “We have to remember we are entering the spring, which is a season when, traditionally, the disease can spread more easily, and it can find its way when people are susceptible. The vaccine is the tool that can help, and we have to act now and make sure it’s offered on time.”
 

A version of this article appeared on Medscape.com.

“Measles should be a memory, not a present risk,” Quique Bassat, MBBS, PhD, director general of the Barcelona Institute of Global Health, told this news organization.

That is certainly not the case right now in some parts of Europe. The World Health Organization (WHO) says the European Region is experiencing an alarming rise in cases, and urgent action is needed. Healthcare professionals are trying to gain control over measles outbreaks and roll out vaccination catch-up campaigns.

“What we are seeing currently is an almost 45-fold rise in measles cases in the WHO European Region,” Siddhartha Datta, MD, European regional advisor on vaccine-preventable diseases and immunization for the WHO, told this news organization. “In 2022, there were 940 cases, and in 2023 till November, it was around 42,000 plus. Between 2020 and 2022, we have seen 1.8 million children who have missed their measles vaccine doses.”
 

Lapses in Vaccinations

The overriding reason for the resurgence of measles is a backslide in vaccination coverage during the COVID-19 pandemic.

“During the COVID pandemic, we had a 5% decrease in coverage for most of the vaccines, and we are still seeing the consequences,” explained Dr. Bassat. “Measles is the perfect example of when you have a small drop of coverage you get outbreaks, as it’s extremely infectious and complicated to control.”

Reported national coverage with the first dose of measles-containing vaccine in the European Region fell from 96% in 2019 to 93% in 2022. Second-dose coverage fell from 92% in 2019 to 91% in 2022.

“You need to have 95% of the population vaccinated if you want herd immunity,” Dr. Bassat said.
 

Variation Across Europe

The WHO European Region comprises 53 countries, including Russia and some countries in central Asia. Its figures show Kazakhstan had the most recorded cases of measles last year, at more than 13,000, followed by the Russian Federation.

Romania declared a national epidemic in December 2023. Dr. Datta said there have also been outbreaks in Austria and France.

The UK Health Security Agency declared a major incident in January 2024 because of a surge in cases. From October 2023 to January 2024, there were 347 lab-confirmed cases of measles in England, with 127 of these confirmed in January. The West Midlands is an area of particular concern.

“It was not as though everything was rosy before COVID,” said Dr. Datta. “We saw wide variation in the coverage rates before the pandemic. Some countries weren’t doing as well. More particularly between some communities or municipalities, there were wide variations, and COVID-19 exacerbated the inequities in coverage. What we are seeing now is a combination of gaps before and after the pandemic, so it’s a compound problem.”

Belgium has also seen a measles resurgence, but not as many cases as the year before the pandemic. Laura Cornelissen, MD, works at the Belgian Public Health Institute, Sciensano, where she leads a team working on vaccine-preventable diseases.

She told this news organization: “We did observe a significant rise in cases and several clusters in 2023, compared to the very low numbers that were observed during the COVID-19 years. Preliminary figures indicate 85 measles cases for Belgium in 2023, leading to at least 26 hospitalizations. This is compared with eight cases for 2022, seven in 2021, and 47 in 2020; but 480 cases in the pre-pandemic year 2019.”

Sabrina Bacci, MD, head of vaccine-preventable diseases and immunization at the European Centre of Disease Control, told this news organization: “There have been a high number of cases in Romania and smaller outbreaks in other countries. However, there are a number of European countries which haven’t seen measles. Even though we have this variation between the different European countries, the tools to respond to outbreaks are the same.”
 

Vaccine Hesitance

Vaccine hesitance or even refusal is on the rise in Europe and elsewhere in the world.

“We can see from behavioral insights that, during COVID, people’s trust on vaccines, healthcare systems, and the government in general has gone down,” said Dr. Datta. “There had been skepticism before about the MMR jab causing autism, which was proved wrong, but vaccine skepticism shown throughout COVID is now showing its head in routine vaccine systems.”

The rise of so-called anti-vaxxers and associated fake conspiracy theories, including a mistrust of Big Pharma, hasn’t been helpful for encouraging essential childhood vaccination uptake, like measles, mumps, and rubella (MMR).

But the MMR vaccine backslide does not only originate in the pandemic.

Vanessa Saliba, consultant epidemiologist at the UK Health Security Agency, said: “MMR vaccine coverage has been falling for the last decade, with 1 out of 10 children starting school in England not protected.”

It could be that some people have religious concerns about the use of pork gelatin as a stabilizer in MMR vaccines. An alternative vaccine that does not contain pork gelatin can be requested.

Doctors and others in healthcare have a pivotal role to play when it comes to getting on top of the surges and educating patients, according to Dr. Bacci. “Healthcare professionals are the most precious resource we have, as they are the ones on the frontline explaining the importance of vaccination to their patients. It’s a very important dialogue.”
 

Clinics and Catch-Up Campaigns

Intensified routine immunization clinics and catch-up campaigns have been established in countries across Europe where they are needed.

Countries with large outbreaks are carrying out case investigations, identifying and vaccinating susceptible contacts, and generally raising awareness and implementing outbreak response immunization.

“Countries are really making good efforts and are systematically catching up the children who have missed their doses in the last 2 years. But the recovery to the 2019 levels has been slow, and more efforts and energy [need] to be put into this. We understand healthcare systems are stretched out from COVID, but this is not the time to lower our guard,” Dr. Datta said.

“Some countries are more proactive than others,” added Dr. Bassat. “Measles is an example of a disease where you typically organize catch-up campaigns. Measles has one of the highest reproductive numbers, as in the absence of preventive measures one infected person infects 14-16 others.”

All countries, even if they haven’t yet experienced measles outbreaks, are being urged by European healthcare authorities to look at potential immunity gaps and address them immediately.
 

When Will It Get Back to Normal?

“Measles was a disease that was targeted for elimination, but because of these outbreaks, we are seeing it almost everywhere again. We need to be careful and get on top of this,” warned Dr. Bassat.

Dr. Datta said it’s up to member states, decision-makers, healthcare leaders, and parents to come together to raise the immunity profiles of the European population. “Vaccination is a shared responsibility. The tools are effective. We just need to be ahead of the virus, and that is the challenge.”

Dr. Bacci added, “We have to remember we are entering the spring, which is a season when, traditionally, the disease can spread more easily, and it can find its way when people are susceptible. The vaccine is the tool that can help, and we have to act now and make sure it’s offered on time.”
 

A version of this article appeared on Medscape.com.

“Measles should be a memory, not a present risk,” Quique Bassat, MBBS, PhD, director general of the Barcelona Institute of Global Health, told this news organization.

That is certainly not the case right now in some parts of Europe. The World Health Organization (WHO) says the European Region is experiencing an alarming rise in cases, and urgent action is needed. Healthcare professionals are trying to gain control over measles outbreaks and roll out vaccination catch-up campaigns.

“What we are seeing currently is an almost 45-fold rise in measles cases in the WHO European Region,” Siddhartha Datta, MD, European regional advisor on vaccine-preventable diseases and immunization for the WHO, told this news organization. “In 2022, there were 940 cases, and in 2023 till November, it was around 42,000 plus. Between 2020 and 2022, we have seen 1.8 million children who have missed their measles vaccine doses.”
 

Lapses in Vaccinations

The overriding reason for the resurgence of measles is a backslide in vaccination coverage during the COVID-19 pandemic.

“During the COVID pandemic, we had a 5% decrease in coverage for most of the vaccines, and we are still seeing the consequences,” explained Dr. Bassat. “Measles is the perfect example of when you have a small drop of coverage you get outbreaks, as it’s extremely infectious and complicated to control.”

Reported national coverage with the first dose of measles-containing vaccine in the European Region fell from 96% in 2019 to 93% in 2022. Second-dose coverage fell from 92% in 2019 to 91% in 2022.

“You need to have 95% of the population vaccinated if you want herd immunity,” Dr. Bassat said.
 

Variation Across Europe

The WHO European Region comprises 53 countries, including Russia and some countries in central Asia. Its figures show Kazakhstan had the most recorded cases of measles last year, at more than 13,000, followed by the Russian Federation.

Romania declared a national epidemic in December 2023. Dr. Datta said there have also been outbreaks in Austria and France.

The UK Health Security Agency declared a major incident in January 2024 because of a surge in cases. From October 2023 to January 2024, there were 347 lab-confirmed cases of measles in England, with 127 of these confirmed in January. The West Midlands is an area of particular concern.

“It was not as though everything was rosy before COVID,” said Dr. Datta. “We saw wide variation in the coverage rates before the pandemic. Some countries weren’t doing as well. More particularly between some communities or municipalities, there were wide variations, and COVID-19 exacerbated the inequities in coverage. What we are seeing now is a combination of gaps before and after the pandemic, so it’s a compound problem.”

Belgium has also seen a measles resurgence, but not as many cases as the year before the pandemic. Laura Cornelissen, MD, works at the Belgian Public Health Institute, Sciensano, where she leads a team working on vaccine-preventable diseases.

She told this news organization: “We did observe a significant rise in cases and several clusters in 2023, compared to the very low numbers that were observed during the COVID-19 years. Preliminary figures indicate 85 measles cases for Belgium in 2023, leading to at least 26 hospitalizations. This is compared with eight cases for 2022, seven in 2021, and 47 in 2020; but 480 cases in the pre-pandemic year 2019.”

Sabrina Bacci, MD, head of vaccine-preventable diseases and immunization at the European Centre of Disease Control, told this news organization: “There have been a high number of cases in Romania and smaller outbreaks in other countries. However, there are a number of European countries which haven’t seen measles. Even though we have this variation between the different European countries, the tools to respond to outbreaks are the same.”
 

Vaccine Hesitance

Vaccine hesitance or even refusal is on the rise in Europe and elsewhere in the world.

“We can see from behavioral insights that, during COVID, people’s trust on vaccines, healthcare systems, and the government in general has gone down,” said Dr. Datta. “There had been skepticism before about the MMR jab causing autism, which was proved wrong, but vaccine skepticism shown throughout COVID is now showing its head in routine vaccine systems.”

The rise of so-called anti-vaxxers and associated fake conspiracy theories, including a mistrust of Big Pharma, hasn’t been helpful for encouraging essential childhood vaccination uptake, like measles, mumps, and rubella (MMR).

But the MMR vaccine backslide does not only originate in the pandemic.

Vanessa Saliba, consultant epidemiologist at the UK Health Security Agency, said: “MMR vaccine coverage has been falling for the last decade, with 1 out of 10 children starting school in England not protected.”

It could be that some people have religious concerns about the use of pork gelatin as a stabilizer in MMR vaccines. An alternative vaccine that does not contain pork gelatin can be requested.

Doctors and others in healthcare have a pivotal role to play when it comes to getting on top of the surges and educating patients, according to Dr. Bacci. “Healthcare professionals are the most precious resource we have, as they are the ones on the frontline explaining the importance of vaccination to their patients. It’s a very important dialogue.”
 

Clinics and Catch-Up Campaigns

Intensified routine immunization clinics and catch-up campaigns have been established in countries across Europe where they are needed.

Countries with large outbreaks are carrying out case investigations, identifying and vaccinating susceptible contacts, and generally raising awareness and implementing outbreak response immunization.

“Countries are really making good efforts and are systematically catching up the children who have missed their doses in the last 2 years. But the recovery to the 2019 levels has been slow, and more efforts and energy [need] to be put into this. We understand healthcare systems are stretched out from COVID, but this is not the time to lower our guard,” Dr. Datta said.

“Some countries are more proactive than others,” added Dr. Bassat. “Measles is an example of a disease where you typically organize catch-up campaigns. Measles has one of the highest reproductive numbers, as in the absence of preventive measures one infected person infects 14-16 others.”

All countries, even if they haven’t yet experienced measles outbreaks, are being urged by European healthcare authorities to look at potential immunity gaps and address them immediately.
 

When Will It Get Back to Normal?

“Measles was a disease that was targeted for elimination, but because of these outbreaks, we are seeing it almost everywhere again. We need to be careful and get on top of this,” warned Dr. Bassat.

Dr. Datta said it’s up to member states, decision-makers, healthcare leaders, and parents to come together to raise the immunity profiles of the European population. “Vaccination is a shared responsibility. The tools are effective. We just need to be ahead of the virus, and that is the challenge.”

Dr. Bacci added, “We have to remember we are entering the spring, which is a season when, traditionally, the disease can spread more easily, and it can find its way when people are susceptible. The vaccine is the tool that can help, and we have to act now and make sure it’s offered on time.”
 

A version of this article appeared on Medscape.com.

A journal and publisher have retracted three papers about abortion, including one that has been used in court cases to support the suspension of FDA approval for mifepristone, aka an “abortion pill.”

Sage, the publisher of Health Services Research and Managerial Epidemiology, announced the retractions yesterday and posted a retraction notice covering the three articles.

For one of those articles, initially flagged by a reader, “an independent reviewer with expertise in statistical analyses evaluated the concerns and opined that the article’s presentation of the data in Figures 2 and 3 leads to an inaccurate conclusion and that the composition of the cohort studied has problems that could affect the article’s conclusions,” according to the notice.

The notice also said Sage “confirmed that all but one of the article’s authors had an affiliation with one or more of Charlotte Lozier Institute, Elliot Institute, and American Association of Pro-Life Obstetricians and Gynecologists, all pro-life advocacy organizations, despite having declared they had no conflicts of interest when they submitted the article for publication or in the article itself.” 

One of the peer reviewers, Sage learned, “was affiliated with Charlotte Lozier Institute at the time of the review,” leading the publisher and journal editor to determine “the peer review for initial publication was unreliable.” That referee also reviewed the other two now-retracted papers, according to Sage.

James Studnicki, the lead author of the three papers, told Retraction Watch the retractions were “a blatant attempt to discredit excellent research which is incongruent with a preferred abortion narrative.” He told The Daily Wire, a conservative news outlet that was first to report on the retractions, the move was “completely unjustified.” The Daily Wire notes that “The Supreme Court is set to hear arguments in March on the legality of restricting the abortion pill based on [Judge Matthew] Kacsmaryk’s ruling, proceedings that will certainly be impacted by the retractions.”

Sage had subjected one of the papers to an expression of concern in August 2023, saying they were investigating “potential issues regarding the representation of data in the article and author conflicts of interest” after being alerted by a reader. As News From The States reported then, the notice came after Chris Adkins, a professor at South University who teaches pharmaceutical sciences, raised concerns with Sage. As News From The States noted in August:

Kacsmaryk leaned hard on a 2021 study that was designed, funded and produced by the research arm of one of the most powerful anti-abortion political groups in the U.S. The judge cited this paper — which looked at Medicaid patients’ visits to the emergency room within 30 days of having an abortion — to justify that a group of anti-abortion doctors and medical groups have legal standing to force the FDA to recall mifepristone.

In a point-by-point response to Sage’s critiques of the paper sent to the publisher in November and now shared with Retraction Watch, Studnicki and colleagues pointed out they had noted their affiliations in the original manuscript and the then-proposed retractions “misrepresent ICMJE disclosure standards,” referring to the International Committee of Medical Journal Editors’ guidelines. They also call some of the post-publication peer reviewers’ critiques “factually incorrect” and “unfounded.” They conclude:

No single specific finding in any of the three papers has been explicitly challenged, let alone invalidated.

There is no evidence of a major error, miscalculation, fabrication, or falsification.

There is no breach of any of the COPE guidelines that could permit Sage to retract any of our published papers.

The retraction of any of these papers, let alone all three, is demonstrably unwarranted.

Adkins told Retraction Watch he is “pleased the journal approached my concerns with legitimate and serious consideration.” He continued:

It is reassuring that my initial concerns with the 2021 Studnicki et al. article were verified and affirmed by other experts. Despite the length of time spanning my initial communications with the journal and today’s retractions, I understand that thorough investigations and re-review processes take time. Given that these now-retracted articles have been excessively cited by parties involved in ongoing federal judicial cases, now positioned before the SCOTUS, Sage’s retractions should help our courts remain informed by the highest standards and quality in scientific and medical evidence.

Update, 2/6/24, 2100 UTC: We note that — contrary to best industry practices described by the Committee on Publication Ethics — Sage has removed the original versions of the articles. They are available at these links:

“A Longitudinal Cohort Study of Emergency Room Utilization Following Mifepristone Chemical and Surgical Abortions, 1999–2015”

“Doctors Who Perform Abortions: Their Characteristics and Patterns of Holding and Using Hospital Privileges”

“A Post Hoc Exploratory Analysis: Induced Abortion Complications Mistaken for Miscarriage in the Emergency Room are a Risk Factor for Hospitalization”

DISCLOSURE: Adam Marcus, a cofounder of Retraction Watch, is an editor at Medscape.

A version of this article appeared on Medscape.com.

A journal and publisher have retracted three papers about abortion, including one that has been used in court cases to support the suspension of FDA approval for mifepristone, aka an “abortion pill.”

Sage, the publisher of Health Services Research and Managerial Epidemiology, announced the retractions yesterday and posted a retraction notice covering the three articles.

For one of those articles, initially flagged by a reader, “an independent reviewer with expertise in statistical analyses evaluated the concerns and opined that the article’s presentation of the data in Figures 2 and 3 leads to an inaccurate conclusion and that the composition of the cohort studied has problems that could affect the article’s conclusions,” according to the notice.

The notice also said Sage “confirmed that all but one of the article’s authors had an affiliation with one or more of Charlotte Lozier Institute, Elliot Institute, and American Association of Pro-Life Obstetricians and Gynecologists, all pro-life advocacy organizations, despite having declared they had no conflicts of interest when they submitted the article for publication or in the article itself.” 

One of the peer reviewers, Sage learned, “was affiliated with Charlotte Lozier Institute at the time of the review,” leading the publisher and journal editor to determine “the peer review for initial publication was unreliable.” That referee also reviewed the other two now-retracted papers, according to Sage.

James Studnicki, the lead author of the three papers, told Retraction Watch the retractions were “a blatant attempt to discredit excellent research which is incongruent with a preferred abortion narrative.” He told The Daily Wire, a conservative news outlet that was first to report on the retractions, the move was “completely unjustified.” The Daily Wire notes that “The Supreme Court is set to hear arguments in March on the legality of restricting the abortion pill based on [Judge Matthew] Kacsmaryk’s ruling, proceedings that will certainly be impacted by the retractions.”

Sage had subjected one of the papers to an expression of concern in August 2023, saying they were investigating “potential issues regarding the representation of data in the article and author conflicts of interest” after being alerted by a reader. As News From The States reported then, the notice came after Chris Adkins, a professor at South University who teaches pharmaceutical sciences, raised concerns with Sage. As News From The States noted in August:

Kacsmaryk leaned hard on a 2021 study that was designed, funded and produced by the research arm of one of the most powerful anti-abortion political groups in the U.S. The judge cited this paper — which looked at Medicaid patients’ visits to the emergency room within 30 days of having an abortion — to justify that a group of anti-abortion doctors and medical groups have legal standing to force the FDA to recall mifepristone.

In a point-by-point response to Sage’s critiques of the paper sent to the publisher in November and now shared with Retraction Watch, Studnicki and colleagues pointed out they had noted their affiliations in the original manuscript and the then-proposed retractions “misrepresent ICMJE disclosure standards,” referring to the International Committee of Medical Journal Editors’ guidelines. They also call some of the post-publication peer reviewers’ critiques “factually incorrect” and “unfounded.” They conclude:

No single specific finding in any of the three papers has been explicitly challenged, let alone invalidated.

There is no evidence of a major error, miscalculation, fabrication, or falsification.

There is no breach of any of the COPE guidelines that could permit Sage to retract any of our published papers.

The retraction of any of these papers, let alone all three, is demonstrably unwarranted.

Adkins told Retraction Watch he is “pleased the journal approached my concerns with legitimate and serious consideration.” He continued:

It is reassuring that my initial concerns with the 2021 Studnicki et al. article were verified and affirmed by other experts. Despite the length of time spanning my initial communications with the journal and today’s retractions, I understand that thorough investigations and re-review processes take time. Given that these now-retracted articles have been excessively cited by parties involved in ongoing federal judicial cases, now positioned before the SCOTUS, Sage’s retractions should help our courts remain informed by the highest standards and quality in scientific and medical evidence.

Update, 2/6/24, 2100 UTC: We note that — contrary to best industry practices described by the Committee on Publication Ethics — Sage has removed the original versions of the articles. They are available at these links:

“A Longitudinal Cohort Study of Emergency Room Utilization Following Mifepristone Chemical and Surgical Abortions, 1999–2015”

“Doctors Who Perform Abortions: Their Characteristics and Patterns of Holding and Using Hospital Privileges”

“A Post Hoc Exploratory Analysis: Induced Abortion Complications Mistaken for Miscarriage in the Emergency Room are a Risk Factor for Hospitalization”

DISCLOSURE: Adam Marcus, a cofounder of Retraction Watch, is an editor at Medscape.

A version of this article appeared on Medscape.com.

A journal and publisher have retracted three papers about abortion, including one that has been used in court cases to support the suspension of FDA approval for mifepristone, aka an “abortion pill.”

Sage, the publisher of Health Services Research and Managerial Epidemiology, announced the retractions yesterday and posted a retraction notice covering the three articles.

For one of those articles, initially flagged by a reader, “an independent reviewer with expertise in statistical analyses evaluated the concerns and opined that the article’s presentation of the data in Figures 2 and 3 leads to an inaccurate conclusion and that the composition of the cohort studied has problems that could affect the article’s conclusions,” according to the notice.

The notice also said Sage “confirmed that all but one of the article’s authors had an affiliation with one or more of Charlotte Lozier Institute, Elliot Institute, and American Association of Pro-Life Obstetricians and Gynecologists, all pro-life advocacy organizations, despite having declared they had no conflicts of interest when they submitted the article for publication or in the article itself.” 

One of the peer reviewers, Sage learned, “was affiliated with Charlotte Lozier Institute at the time of the review,” leading the publisher and journal editor to determine “the peer review for initial publication was unreliable.” That referee also reviewed the other two now-retracted papers, according to Sage.

James Studnicki, the lead author of the three papers, told Retraction Watch the retractions were “a blatant attempt to discredit excellent research which is incongruent with a preferred abortion narrative.” He told The Daily Wire, a conservative news outlet that was first to report on the retractions, the move was “completely unjustified.” The Daily Wire notes that “The Supreme Court is set to hear arguments in March on the legality of restricting the abortion pill based on [Judge Matthew] Kacsmaryk’s ruling, proceedings that will certainly be impacted by the retractions.”

Sage had subjected one of the papers to an expression of concern in August 2023, saying they were investigating “potential issues regarding the representation of data in the article and author conflicts of interest” after being alerted by a reader. As News From The States reported then, the notice came after Chris Adkins, a professor at South University who teaches pharmaceutical sciences, raised concerns with Sage. As News From The States noted in August:

Kacsmaryk leaned hard on a 2021 study that was designed, funded and produced by the research arm of one of the most powerful anti-abortion political groups in the U.S. The judge cited this paper — which looked at Medicaid patients’ visits to the emergency room within 30 days of having an abortion — to justify that a group of anti-abortion doctors and medical groups have legal standing to force the FDA to recall mifepristone.

In a point-by-point response to Sage’s critiques of the paper sent to the publisher in November and now shared with Retraction Watch, Studnicki and colleagues pointed out they had noted their affiliations in the original manuscript and the then-proposed retractions “misrepresent ICMJE disclosure standards,” referring to the International Committee of Medical Journal Editors’ guidelines. They also call some of the post-publication peer reviewers’ critiques “factually incorrect” and “unfounded.” They conclude:

No single specific finding in any of the three papers has been explicitly challenged, let alone invalidated.

There is no evidence of a major error, miscalculation, fabrication, or falsification.

There is no breach of any of the COPE guidelines that could permit Sage to retract any of our published papers.

The retraction of any of these papers, let alone all three, is demonstrably unwarranted.

Adkins told Retraction Watch he is “pleased the journal approached my concerns with legitimate and serious consideration.” He continued:

It is reassuring that my initial concerns with the 2021 Studnicki et al. article were verified and affirmed by other experts. Despite the length of time spanning my initial communications with the journal and today’s retractions, I understand that thorough investigations and re-review processes take time. Given that these now-retracted articles have been excessively cited by parties involved in ongoing federal judicial cases, now positioned before the SCOTUS, Sage’s retractions should help our courts remain informed by the highest standards and quality in scientific and medical evidence.

Update, 2/6/24, 2100 UTC: We note that — contrary to best industry practices described by the Committee on Publication Ethics — Sage has removed the original versions of the articles. They are available at these links:

“A Longitudinal Cohort Study of Emergency Room Utilization Following Mifepristone Chemical and Surgical Abortions, 1999–2015”

“Doctors Who Perform Abortions: Their Characteristics and Patterns of Holding and Using Hospital Privileges”

“A Post Hoc Exploratory Analysis: Induced Abortion Complications Mistaken for Miscarriage in the Emergency Room are a Risk Factor for Hospitalization”

DISCLOSURE: Adam Marcus, a cofounder of Retraction Watch, is an editor at Medscape.

A version of this article appeared on Medscape.com.

Men prescribed drugs to treat newly diagnosed erectile dysfunction (ED) are 18% less likely to develop Alzheimer’s disease (AD) during a 5-year follow-up period, new research shows. 

The study is the second in recent years to suggest an association between the use of phosphodiesterase type 5 inhibitors (PDE5Is) such as sildenafil (Viagra) or tadalafil (Cialis) and AD risk. The findings contradict those in a third study, reported by this news organization, that showed no link between the two. 

Although the research is interesting, outside experts noted that there is no evidence that the drugs can treat AD and urge caution when interpreting the findings. 

Investigators agree but believe that the results offer a direction for future studies and underscore the importance of investigating whether existing approved therapies can be repurposed to treat AD. 

“The positive findings from our large study in over 250,000 men is promising and can be used to enhance research capacity and knowledge, with a potential future impact on clinical use and public health policy,” senior author Ruth Brauer, PhD, of the University College London, told this news organization.

“However, before recommending PDE5I are used to reduce the risk of AD, more work is required to validate the findings of our work, particularly in a more generalizable population that includes women and men without erectile dysfunction,” she continued.

The findings were published online February 7 in Neurology.

Strong Association

The study drew on primary healthcare data from the United Kingdom and included 269,725 men (average age, 59 years) with newly diagnosed ED, 55% of whom had received prescriptions for PDE5Is. 

Participants were free from memory or cognitive issues when the study began and were followed for a median of 5.1 years. Investigators accounted for a range of potential AD risk factors, including smoking status, alcohol use, body mass index, hypertension, diabetes, depression, anxiety, and concomitant medication use.

During the study period, 749 in the PDE5I group were diagnosed with AD, corresponding to a rate of 8.1 cases per 10,000 person-years. Among those who did not take the drugs, 370 developed AD, corresponding to a rate of 9.7 cases per 10,000 person-years.

Overall, initiation of a PDE5I was associated with an 18% lower risk for AD (adjusted hazard ration [aHR], 0.82; 95% CI, 0.72-0.93) compared with those with no prescriptions. 

The association was stronger in people aged 70 years or older and those with a history of hypertension or diabetes. The greatest risk reduction was found in people with the most prescriptions during the study period. Those with 21-50 prescriptions had a 44% lower risk for AD (aHR, 0.56; 95% CI, 0.43-0.73) and those with more than 50 were 35% less likely to be diagnosed with AD (aHR, 0.65; 95% CI, 0.49-0.87).

There was no association with AD risk in individuals who received fewer than 20 prescriptions. 

Investigators also analyzed associations after introducing a 1- and 3-year lag period after cohort entry to address the latent period between AD onset and diagnosis. The primary findings held with a 1-year lag period but lost significance with the inclusion of a 3-year lag period.

In subgroup analyses, investigators found evidence of reduced AD risk in those who received prescriptions for sildenafil (aHR, 0.81; 95% CI, 0.71-0.93), but there was no evidence for reduced risk compared with nonusers in those who received tadalafil and vardenafil.

Lower AD risk was found in patients with hypertension, diabetes, and in men aged 70 years or older, but there was no association in younger men or those with no history of hypertension or diabetes. 

Although investigators controlled for a wide range of potential risk factors, Dr. Brauer noted that unmeasured confounders such as physical and sexual activity, which were not tracked and may predict PDE5I exposure, may have affected the results. 

Interpret With Caution

Commenting on the findings, Ozama Ismail, PhD, Alzheimer’s Association director of scientific programs, noted that in addition to the limitations cited by the study authors, AD diagnoses were not made with the “gold standard” testing that typically includes imaging biomarkers and postmortem assessments. 

“While this study is interesting and adds to a potential association, there is no evidence that these drugs are able to treat Alzheimer’s disease,” said Dr. Brauer, who was not part of the current study. 

“People should not use over-the-counter phosphodiesterase type 5 inhibitors for prevention of Alzheimer’s or other dementias based on this very preliminary finding. Always consult with your physician before starting or changing your medications,” he cautioned.

However, Dr. Ismael added that the study does highlight a potential new avenue for drug repurposing. 

“Repurposing of existing, already-approved treatments can be a valuable part of drug development because, through already-completed testing, we know much about their safety and side effects,” which can decrease cost and time needed for studies, he said. 

“When considering repurposing an existing drug to an Alzheimer’s treatment, however, it is often important to conduct new studies over longer periods of time and in older people that reflect the diversity of individuals living with Alzheimer’s disease,” Dr. Ismael said.

Randomized Trials Needed

Dr. Brauer agreed, offering that such a trial should also include people with mild cognitive impairment and measure the effects of PDE5Is given in predefined doses plus an acetylcholinesterase inhibitor or placebo plus an acetylcholinesterase inhibitor. 

“The primary outcome would be the change in baseline cognitive function,” she said. “This approach would provide a comprehensive understanding of the potential therapeutic benefits of PDE5I and AD.”

Studies are also needed to better understand the mechanisms by which these drugs might influence AD risk, Sevil Yasar, MD, PhD, and Lolita Nidadavolu, MD, PhD, from the Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, noted in an accompanying editorial.

The strong association between PDE5I use and AD risk in people with a history of hypertension or diabetes suggests “a potential neuroprotective effect through a vascular pathway,” they wrote.

In vitro studies on the role of inflammation and clearance of beta-amyloid could strengthen findings from studies like this one, and in vivo studies could help explain the mechanisms behind PDE5I use and lower AD risk, Dr. Yasar and Dr. Nidadavolu noted. 

“In the end, however, further observational studies exploring mechanisms will not prove a causal association,” they wrote. “A well-designed randomized controlled trial is needed before PDE5I drugs can be prescribed for AD prevention.”

The study was unfunded. The study and editorial authors and Dr. Ismail report no relevant financial conflicts. 
 

A version of this article appeared on Medscape.com.

Men prescribed drugs to treat newly diagnosed erectile dysfunction (ED) are 18% less likely to develop Alzheimer’s disease (AD) during a 5-year follow-up period, new research shows. 

The study is the second in recent years to suggest an association between the use of phosphodiesterase type 5 inhibitors (PDE5Is) such as sildenafil (Viagra) or tadalafil (Cialis) and AD risk. The findings contradict those in a third study, reported by this news organization, that showed no link between the two. 

Although the research is interesting, outside experts noted that there is no evidence that the drugs can treat AD and urge caution when interpreting the findings. 

Investigators agree but believe that the results offer a direction for future studies and underscore the importance of investigating whether existing approved therapies can be repurposed to treat AD. 

“The positive findings from our large study in over 250,000 men is promising and can be used to enhance research capacity and knowledge, with a potential future impact on clinical use and public health policy,” senior author Ruth Brauer, PhD, of the University College London, told this news organization.

“However, before recommending PDE5I are used to reduce the risk of AD, more work is required to validate the findings of our work, particularly in a more generalizable population that includes women and men without erectile dysfunction,” she continued.

The findings were published online February 7 in Neurology.

Strong Association

The study drew on primary healthcare data from the United Kingdom and included 269,725 men (average age, 59 years) with newly diagnosed ED, 55% of whom had received prescriptions for PDE5Is. 

Participants were free from memory or cognitive issues when the study began and were followed for a median of 5.1 years. Investigators accounted for a range of potential AD risk factors, including smoking status, alcohol use, body mass index, hypertension, diabetes, depression, anxiety, and concomitant medication use.

During the study period, 749 in the PDE5I group were diagnosed with AD, corresponding to a rate of 8.1 cases per 10,000 person-years. Among those who did not take the drugs, 370 developed AD, corresponding to a rate of 9.7 cases per 10,000 person-years.

Overall, initiation of a PDE5I was associated with an 18% lower risk for AD (adjusted hazard ration [aHR], 0.82; 95% CI, 0.72-0.93) compared with those with no prescriptions. 

The association was stronger in people aged 70 years or older and those with a history of hypertension or diabetes. The greatest risk reduction was found in people with the most prescriptions during the study period. Those with 21-50 prescriptions had a 44% lower risk for AD (aHR, 0.56; 95% CI, 0.43-0.73) and those with more than 50 were 35% less likely to be diagnosed with AD (aHR, 0.65; 95% CI, 0.49-0.87).

There was no association with AD risk in individuals who received fewer than 20 prescriptions. 

Investigators also analyzed associations after introducing a 1- and 3-year lag period after cohort entry to address the latent period between AD onset and diagnosis. The primary findings held with a 1-year lag period but lost significance with the inclusion of a 3-year lag period.

In subgroup analyses, investigators found evidence of reduced AD risk in those who received prescriptions for sildenafil (aHR, 0.81; 95% CI, 0.71-0.93), but there was no evidence for reduced risk compared with nonusers in those who received tadalafil and vardenafil.

Lower AD risk was found in patients with hypertension, diabetes, and in men aged 70 years or older, but there was no association in younger men or those with no history of hypertension or diabetes. 

Although investigators controlled for a wide range of potential risk factors, Dr. Brauer noted that unmeasured confounders such as physical and sexual activity, which were not tracked and may predict PDE5I exposure, may have affected the results. 

Interpret With Caution

Commenting on the findings, Ozama Ismail, PhD, Alzheimer’s Association director of scientific programs, noted that in addition to the limitations cited by the study authors, AD diagnoses were not made with the “gold standard” testing that typically includes imaging biomarkers and postmortem assessments. 

“While this study is interesting and adds to a potential association, there is no evidence that these drugs are able to treat Alzheimer’s disease,” said Dr. Brauer, who was not part of the current study. 

“People should not use over-the-counter phosphodiesterase type 5 inhibitors for prevention of Alzheimer’s or other dementias based on this very preliminary finding. Always consult with your physician before starting or changing your medications,” he cautioned.

However, Dr. Ismael added that the study does highlight a potential new avenue for drug repurposing. 

“Repurposing of existing, already-approved treatments can be a valuable part of drug development because, through already-completed testing, we know much about their safety and side effects,” which can decrease cost and time needed for studies, he said. 

“When considering repurposing an existing drug to an Alzheimer’s treatment, however, it is often important to conduct new studies over longer periods of time and in older people that reflect the diversity of individuals living with Alzheimer’s disease,” Dr. Ismael said.

Randomized Trials Needed

Dr. Brauer agreed, offering that such a trial should also include people with mild cognitive impairment and measure the effects of PDE5Is given in predefined doses plus an acetylcholinesterase inhibitor or placebo plus an acetylcholinesterase inhibitor. 

“The primary outcome would be the change in baseline cognitive function,” she said. “This approach would provide a comprehensive understanding of the potential therapeutic benefits of PDE5I and AD.”

Studies are also needed to better understand the mechanisms by which these drugs might influence AD risk, Sevil Yasar, MD, PhD, and Lolita Nidadavolu, MD, PhD, from the Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, noted in an accompanying editorial.

The strong association between PDE5I use and AD risk in people with a history of hypertension or diabetes suggests “a potential neuroprotective effect through a vascular pathway,” they wrote.

In vitro studies on the role of inflammation and clearance of beta-amyloid could strengthen findings from studies like this one, and in vivo studies could help explain the mechanisms behind PDE5I use and lower AD risk, Dr. Yasar and Dr. Nidadavolu noted. 

“In the end, however, further observational studies exploring mechanisms will not prove a causal association,” they wrote. “A well-designed randomized controlled trial is needed before PDE5I drugs can be prescribed for AD prevention.”

The study was unfunded. The study and editorial authors and Dr. Ismail report no relevant financial conflicts. 
 

A version of this article appeared on Medscape.com.

Men prescribed drugs to treat newly diagnosed erectile dysfunction (ED) are 18% less likely to develop Alzheimer’s disease (AD) during a 5-year follow-up period, new research shows. 

The study is the second in recent years to suggest an association between the use of phosphodiesterase type 5 inhibitors (PDE5Is) such as sildenafil (Viagra) or tadalafil (Cialis) and AD risk. The findings contradict those in a third study, reported by this news organization, that showed no link between the two. 

Although the research is interesting, outside experts noted that there is no evidence that the drugs can treat AD and urge caution when interpreting the findings. 

Investigators agree but believe that the results offer a direction for future studies and underscore the importance of investigating whether existing approved therapies can be repurposed to treat AD. 

“The positive findings from our large study in over 250,000 men is promising and can be used to enhance research capacity and knowledge, with a potential future impact on clinical use and public health policy,” senior author Ruth Brauer, PhD, of the University College London, told this news organization.

“However, before recommending PDE5I are used to reduce the risk of AD, more work is required to validate the findings of our work, particularly in a more generalizable population that includes women and men without erectile dysfunction,” she continued.

The findings were published online February 7 in Neurology.

Strong Association

The study drew on primary healthcare data from the United Kingdom and included 269,725 men (average age, 59 years) with newly diagnosed ED, 55% of whom had received prescriptions for PDE5Is. 

Participants were free from memory or cognitive issues when the study began and were followed for a median of 5.1 years. Investigators accounted for a range of potential AD risk factors, including smoking status, alcohol use, body mass index, hypertension, diabetes, depression, anxiety, and concomitant medication use.

During the study period, 749 in the PDE5I group were diagnosed with AD, corresponding to a rate of 8.1 cases per 10,000 person-years. Among those who did not take the drugs, 370 developed AD, corresponding to a rate of 9.7 cases per 10,000 person-years.

Overall, initiation of a PDE5I was associated with an 18% lower risk for AD (adjusted hazard ration [aHR], 0.82; 95% CI, 0.72-0.93) compared with those with no prescriptions. 

The association was stronger in people aged 70 years or older and those with a history of hypertension or diabetes. The greatest risk reduction was found in people with the most prescriptions during the study period. Those with 21-50 prescriptions had a 44% lower risk for AD (aHR, 0.56; 95% CI, 0.43-0.73) and those with more than 50 were 35% less likely to be diagnosed with AD (aHR, 0.65; 95% CI, 0.49-0.87).

There was no association with AD risk in individuals who received fewer than 20 prescriptions. 

Investigators also analyzed associations after introducing a 1- and 3-year lag period after cohort entry to address the latent period between AD onset and diagnosis. The primary findings held with a 1-year lag period but lost significance with the inclusion of a 3-year lag period.

In subgroup analyses, investigators found evidence of reduced AD risk in those who received prescriptions for sildenafil (aHR, 0.81; 95% CI, 0.71-0.93), but there was no evidence for reduced risk compared with nonusers in those who received tadalafil and vardenafil.

Lower AD risk was found in patients with hypertension, diabetes, and in men aged 70 years or older, but there was no association in younger men or those with no history of hypertension or diabetes. 

Although investigators controlled for a wide range of potential risk factors, Dr. Brauer noted that unmeasured confounders such as physical and sexual activity, which were not tracked and may predict PDE5I exposure, may have affected the results. 

Interpret With Caution

Commenting on the findings, Ozama Ismail, PhD, Alzheimer’s Association director of scientific programs, noted that in addition to the limitations cited by the study authors, AD diagnoses were not made with the “gold standard” testing that typically includes imaging biomarkers and postmortem assessments. 

“While this study is interesting and adds to a potential association, there is no evidence that these drugs are able to treat Alzheimer’s disease,” said Dr. Brauer, who was not part of the current study. 

“People should not use over-the-counter phosphodiesterase type 5 inhibitors for prevention of Alzheimer’s or other dementias based on this very preliminary finding. Always consult with your physician before starting or changing your medications,” he cautioned.

However, Dr. Ismael added that the study does highlight a potential new avenue for drug repurposing. 

“Repurposing of existing, already-approved treatments can be a valuable part of drug development because, through already-completed testing, we know much about their safety and side effects,” which can decrease cost and time needed for studies, he said. 

“When considering repurposing an existing drug to an Alzheimer’s treatment, however, it is often important to conduct new studies over longer periods of time and in older people that reflect the diversity of individuals living with Alzheimer’s disease,” Dr. Ismael said.

Randomized Trials Needed

Dr. Brauer agreed, offering that such a trial should also include people with mild cognitive impairment and measure the effects of PDE5Is given in predefined doses plus an acetylcholinesterase inhibitor or placebo plus an acetylcholinesterase inhibitor. 

“The primary outcome would be the change in baseline cognitive function,” she said. “This approach would provide a comprehensive understanding of the potential therapeutic benefits of PDE5I and AD.”

Studies are also needed to better understand the mechanisms by which these drugs might influence AD risk, Sevil Yasar, MD, PhD, and Lolita Nidadavolu, MD, PhD, from the Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, noted in an accompanying editorial.

The strong association between PDE5I use and AD risk in people with a history of hypertension or diabetes suggests “a potential neuroprotective effect through a vascular pathway,” they wrote.

In vitro studies on the role of inflammation and clearance of beta-amyloid could strengthen findings from studies like this one, and in vivo studies could help explain the mechanisms behind PDE5I use and lower AD risk, Dr. Yasar and Dr. Nidadavolu noted. 

“In the end, however, further observational studies exploring mechanisms will not prove a causal association,” they wrote. “A well-designed randomized controlled trial is needed before PDE5I drugs can be prescribed for AD prevention.”

The study was unfunded. The study and editorial authors and Dr. Ismail report no relevant financial conflicts. 
 

A version of this article appeared on Medscape.com.