Conference Coverage

It’s now official: The investigational sodium-glucose cotransporter (SGLT) 1/2 inhibitor sotagliflozin is the first agent clearly shown in a prespecified analysis of randomized trials to improve clinical outcomes in patients with heart failure with reduced ejection fraction (HFpEF).

Researchers who ran the SCORED and SOLOIST-WHF pivotal trials for sotagliflozin first made that claim in November 2020 when reporting top-line results from a prespecified meta-analysis of the two trials during the American Heart Association annual scientific sessions. A follow-up report during the annual scientific sessions of the American College of Cardiology fleshed out the evidence and firmed up their landmark conclusion.

The meta-analysis (Abstract 410-08) included 4,500 patients with type 2 diabetes and diagnosed heart failure at entry; its primary endpoint, which was the same in both trials, was the combined incidence of cardiovascular death and the total number of either hospitalization for heart failure or urgent outpatient visits for heart failure.

Compared with placebo, treatment with sotagliflozin for a median of about 15 months dropped this composite endpoint by a relative 33% among the 1,931 who began the study with a left ventricular ejection fraction (LVEF) of at least 50% (HFpEF), by a relative 22% in the 1,758 patients who entered with an LVEF of less than 40% (patients with heart failure with reduced ejection fraction), and by a relative 43% among the 811 patients who began with an LVEF of 40%-49% (patients with heart failure with mid-range ejection fraction). The relative risk reductions were significant for all three subgroups, Deepak L. Bhatt, MD, reported at the meeting.
 

Equally effective ‘across the full range of LVEFs.’

Perhaps as notable and unprecedented was the further finding that the clinical benefits seen with treatment of patients with type 2 diabetes with sotagliflozin was consistent regardless of the ejection fraction they had at entry. Enrolled patients with baseline LVEFs in the range of 25% received a relative benefit from sotagliflozin treatment that was statistically no different from the benefit seen in patients who entered with an LVEF in the neighborhood of 45%, 65%, or at any other level across the LVEF spectrum, a finding that Dr. Bhatt called “remarkable” during a press briefing. “The results show the benefit of sotagliflozin across the full range of LVEFs.”

“We are very excited in the heart failure world by the SGLT2 inhibitors; we’ve been impressed by their reduction in heart failure hospitalizations, but we wonder about the patients with HFpEF, where we haven’t had a blockbuster drug to give,” said Ileana L. Piña, MD, a heart failure specialist and medical officer with the Food and Drug Administration.

The new findings “look like they could pose a regulatory indication [for sotagliflozin] for patients with type 2 diabetes and heart failure across the entire spectrum of heart failure,” said Christopher M. O’Connor, MD, a heart failure specialist and president of the Inova Heart & Vascular institute in Falls Church, Va., and designated discussant for Dr. Bhatt’s report.

A significant on-treatment reduction in CV death

Other new, notable findings from the meta-analysis included the observation that while treatment with sotagliflozin failed to produce a significant reduction in cardiovascular death, compared with placebo, in the intent-to-treat analysis of all patients and of those with heart failure at baseline (it produced nonsignificant point-estimate reductions of 11% compared with placebo for all patients, and of 23% for patients who began the study with heart failure), it did result in a significant 23% relative risk reduction when the researchers focused on patients while they remained adherent to their sotagliflozin regimen (the on-treatment analysis). This 23% relative reduction appeared among all enrolled patients, as well as in the subgroup that started with diagnosed heart failure.

“Given the totality of data from the SGLT2 inhibitors, I think this is a real finding,” Dr. Bhatt said.

Additional analyses also showed that, among women, treatment with sotagliflozin was linked with significant relative reductions in the primary endpoint of roughly 30% compared with placebo among all patients, and also among those with heart failure at baseline. “HFpEF is a problem particularly in older women, and we showed that the benefit was consistent in men and women,” Dr. Bhatt said.

He acknowledged that results are expected soon from two pivotal trials that are examining two different SGLT2 inhibitors, dapagliflozin and empagliflozin, in patients with HFpEF. “I think there will be a class effect for both SGLT2 inhibitors and sotagliflozin for reducing heart failure events in patients with HFpEF, and I predict that the dapagliflozin and empagliflozin trials will have positive results,” Dr. Bhatt said.

Sotagliflozin differs from the SGLT2 inhibitors by also inhibiting SGLT1, an enzyme found in the gastrointestinal system that, when inhibited, results in increased glucose excretion from the gut and a cut in bloodstream levels of postprandial glucose levels. The Food and Drug Administration accepted data from SCORED and SOLOIST-WHF as part of the evidence the agency is now considering for granting a new drug approval to sotagliflozin.

SCORED and SOLOIST-WHF were initially sponsored by Sanofi, and later by Lexicon Pharmaceuticals. Dr. Bhatt’s institution, Brigham and Women’s Hospital, has received funding from Sanofi and Lexicon Pharmaceuticals. He has been a consultant to and received honoraria from K₂P, Level Ex, and MJH Life Sciences; he has been an adviser to Cardax, Cereno Scientific, Myokardia, Novo Nordisk, Phase Bio, and PLx Pharma; and he has received research funding from numerous companies. Dr. Piña has no relevant disclosures. Dr. O’Connor has been a consultant to Arena, Bayer, Bristol-Myers Squibb, Merck, and Windtree, and he has an ownership interest in Biscardia.

mzoler@mdedge.com

It’s now official: The investigational sodium-glucose cotransporter (SGLT) 1/2 inhibitor sotagliflozin is the first agent clearly shown in a prespecified analysis of randomized trials to improve clinical outcomes in patients with heart failure with reduced ejection fraction (HFpEF).

Researchers who ran the SCORED and SOLOIST-WHF pivotal trials for sotagliflozin first made that claim in November 2020 when reporting top-line results from a prespecified meta-analysis of the two trials during the American Heart Association annual scientific sessions. A follow-up report during the annual scientific sessions of the American College of Cardiology fleshed out the evidence and firmed up their landmark conclusion.

The meta-analysis (Abstract 410-08) included 4,500 patients with type 2 diabetes and diagnosed heart failure at entry; its primary endpoint, which was the same in both trials, was the combined incidence of cardiovascular death and the total number of either hospitalization for heart failure or urgent outpatient visits for heart failure.

Compared with placebo, treatment with sotagliflozin for a median of about 15 months dropped this composite endpoint by a relative 33% among the 1,931 who began the study with a left ventricular ejection fraction (LVEF) of at least 50% (HFpEF), by a relative 22% in the 1,758 patients who entered with an LVEF of less than 40% (patients with heart failure with reduced ejection fraction), and by a relative 43% among the 811 patients who began with an LVEF of 40%-49% (patients with heart failure with mid-range ejection fraction). The relative risk reductions were significant for all three subgroups, Deepak L. Bhatt, MD, reported at the meeting.
 

Equally effective ‘across the full range of LVEFs.’

Perhaps as notable and unprecedented was the further finding that the clinical benefits seen with treatment of patients with type 2 diabetes with sotagliflozin was consistent regardless of the ejection fraction they had at entry. Enrolled patients with baseline LVEFs in the range of 25% received a relative benefit from sotagliflozin treatment that was statistically no different from the benefit seen in patients who entered with an LVEF in the neighborhood of 45%, 65%, or at any other level across the LVEF spectrum, a finding that Dr. Bhatt called “remarkable” during a press briefing. “The results show the benefit of sotagliflozin across the full range of LVEFs.”

“We are very excited in the heart failure world by the SGLT2 inhibitors; we’ve been impressed by their reduction in heart failure hospitalizations, but we wonder about the patients with HFpEF, where we haven’t had a blockbuster drug to give,” said Ileana L. Piña, MD, a heart failure specialist and medical officer with the Food and Drug Administration.

The new findings “look like they could pose a regulatory indication [for sotagliflozin] for patients with type 2 diabetes and heart failure across the entire spectrum of heart failure,” said Christopher M. O’Connor, MD, a heart failure specialist and president of the Inova Heart & Vascular institute in Falls Church, Va., and designated discussant for Dr. Bhatt’s report.

A significant on-treatment reduction in CV death

Other new, notable findings from the meta-analysis included the observation that while treatment with sotagliflozin failed to produce a significant reduction in cardiovascular death, compared with placebo, in the intent-to-treat analysis of all patients and of those with heart failure at baseline (it produced nonsignificant point-estimate reductions of 11% compared with placebo for all patients, and of 23% for patients who began the study with heart failure), it did result in a significant 23% relative risk reduction when the researchers focused on patients while they remained adherent to their sotagliflozin regimen (the on-treatment analysis). This 23% relative reduction appeared among all enrolled patients, as well as in the subgroup that started with diagnosed heart failure.

“Given the totality of data from the SGLT2 inhibitors, I think this is a real finding,” Dr. Bhatt said.

Additional analyses also showed that, among women, treatment with sotagliflozin was linked with significant relative reductions in the primary endpoint of roughly 30% compared with placebo among all patients, and also among those with heart failure at baseline. “HFpEF is a problem particularly in older women, and we showed that the benefit was consistent in men and women,” Dr. Bhatt said.

He acknowledged that results are expected soon from two pivotal trials that are examining two different SGLT2 inhibitors, dapagliflozin and empagliflozin, in patients with HFpEF. “I think there will be a class effect for both SGLT2 inhibitors and sotagliflozin for reducing heart failure events in patients with HFpEF, and I predict that the dapagliflozin and empagliflozin trials will have positive results,” Dr. Bhatt said.

Sotagliflozin differs from the SGLT2 inhibitors by also inhibiting SGLT1, an enzyme found in the gastrointestinal system that, when inhibited, results in increased glucose excretion from the gut and a cut in bloodstream levels of postprandial glucose levels. The Food and Drug Administration accepted data from SCORED and SOLOIST-WHF as part of the evidence the agency is now considering for granting a new drug approval to sotagliflozin.

SCORED and SOLOIST-WHF were initially sponsored by Sanofi, and later by Lexicon Pharmaceuticals. Dr. Bhatt’s institution, Brigham and Women’s Hospital, has received funding from Sanofi and Lexicon Pharmaceuticals. He has been a consultant to and received honoraria from K₂P, Level Ex, and MJH Life Sciences; he has been an adviser to Cardax, Cereno Scientific, Myokardia, Novo Nordisk, Phase Bio, and PLx Pharma; and he has received research funding from numerous companies. Dr. Piña has no relevant disclosures. Dr. O’Connor has been a consultant to Arena, Bayer, Bristol-Myers Squibb, Merck, and Windtree, and he has an ownership interest in Biscardia.

mzoler@mdedge.com

It’s now official: The investigational sodium-glucose cotransporter (SGLT) 1/2 inhibitor sotagliflozin is the first agent clearly shown in a prespecified analysis of randomized trials to improve clinical outcomes in patients with heart failure with reduced ejection fraction (HFpEF).

Researchers who ran the SCORED and SOLOIST-WHF pivotal trials for sotagliflozin first made that claim in November 2020 when reporting top-line results from a prespecified meta-analysis of the two trials during the American Heart Association annual scientific sessions. A follow-up report during the annual scientific sessions of the American College of Cardiology fleshed out the evidence and firmed up their landmark conclusion.

The meta-analysis (Abstract 410-08) included 4,500 patients with type 2 diabetes and diagnosed heart failure at entry; its primary endpoint, which was the same in both trials, was the combined incidence of cardiovascular death and the total number of either hospitalization for heart failure or urgent outpatient visits for heart failure.

Compared with placebo, treatment with sotagliflozin for a median of about 15 months dropped this composite endpoint by a relative 33% among the 1,931 who began the study with a left ventricular ejection fraction (LVEF) of at least 50% (HFpEF), by a relative 22% in the 1,758 patients who entered with an LVEF of less than 40% (patients with heart failure with reduced ejection fraction), and by a relative 43% among the 811 patients who began with an LVEF of 40%-49% (patients with heart failure with mid-range ejection fraction). The relative risk reductions were significant for all three subgroups, Deepak L. Bhatt, MD, reported at the meeting.
 

Equally effective ‘across the full range of LVEFs.’

Perhaps as notable and unprecedented was the further finding that the clinical benefits seen with treatment of patients with type 2 diabetes with sotagliflozin was consistent regardless of the ejection fraction they had at entry. Enrolled patients with baseline LVEFs in the range of 25% received a relative benefit from sotagliflozin treatment that was statistically no different from the benefit seen in patients who entered with an LVEF in the neighborhood of 45%, 65%, or at any other level across the LVEF spectrum, a finding that Dr. Bhatt called “remarkable” during a press briefing. “The results show the benefit of sotagliflozin across the full range of LVEFs.”

“We are very excited in the heart failure world by the SGLT2 inhibitors; we’ve been impressed by their reduction in heart failure hospitalizations, but we wonder about the patients with HFpEF, where we haven’t had a blockbuster drug to give,” said Ileana L. Piña, MD, a heart failure specialist and medical officer with the Food and Drug Administration.

The new findings “look like they could pose a regulatory indication [for sotagliflozin] for patients with type 2 diabetes and heart failure across the entire spectrum of heart failure,” said Christopher M. O’Connor, MD, a heart failure specialist and president of the Inova Heart & Vascular institute in Falls Church, Va., and designated discussant for Dr. Bhatt’s report.

A significant on-treatment reduction in CV death

Other new, notable findings from the meta-analysis included the observation that while treatment with sotagliflozin failed to produce a significant reduction in cardiovascular death, compared with placebo, in the intent-to-treat analysis of all patients and of those with heart failure at baseline (it produced nonsignificant point-estimate reductions of 11% compared with placebo for all patients, and of 23% for patients who began the study with heart failure), it did result in a significant 23% relative risk reduction when the researchers focused on patients while they remained adherent to their sotagliflozin regimen (the on-treatment analysis). This 23% relative reduction appeared among all enrolled patients, as well as in the subgroup that started with diagnosed heart failure.

“Given the totality of data from the SGLT2 inhibitors, I think this is a real finding,” Dr. Bhatt said.

Additional analyses also showed that, among women, treatment with sotagliflozin was linked with significant relative reductions in the primary endpoint of roughly 30% compared with placebo among all patients, and also among those with heart failure at baseline. “HFpEF is a problem particularly in older women, and we showed that the benefit was consistent in men and women,” Dr. Bhatt said.

He acknowledged that results are expected soon from two pivotal trials that are examining two different SGLT2 inhibitors, dapagliflozin and empagliflozin, in patients with HFpEF. “I think there will be a class effect for both SGLT2 inhibitors and sotagliflozin for reducing heart failure events in patients with HFpEF, and I predict that the dapagliflozin and empagliflozin trials will have positive results,” Dr. Bhatt said.

Sotagliflozin differs from the SGLT2 inhibitors by also inhibiting SGLT1, an enzyme found in the gastrointestinal system that, when inhibited, results in increased glucose excretion from the gut and a cut in bloodstream levels of postprandial glucose levels. The Food and Drug Administration accepted data from SCORED and SOLOIST-WHF as part of the evidence the agency is now considering for granting a new drug approval to sotagliflozin.

SCORED and SOLOIST-WHF were initially sponsored by Sanofi, and later by Lexicon Pharmaceuticals. Dr. Bhatt’s institution, Brigham and Women’s Hospital, has received funding from Sanofi and Lexicon Pharmaceuticals. He has been a consultant to and received honoraria from K₂P, Level Ex, and MJH Life Sciences; he has been an adviser to Cardax, Cereno Scientific, Myokardia, Novo Nordisk, Phase Bio, and PLx Pharma; and he has received research funding from numerous companies. Dr. Piña has no relevant disclosures. Dr. O’Connor has been a consultant to Arena, Bayer, Bristol-Myers Squibb, Merck, and Windtree, and he has an ownership interest in Biscardia.

mzoler@mdedge.com

Individuals at increased risk for dementia because of family history can reduce that risk by adopting healthy lifestyle behaviors, data from more than 300,000 adults aged 50-73 years suggest.

Having a parent or sibling with dementia can increase a person’s risk of developing dementia themselves by nearly 75%, compared with someone with no first-degree family history of dementia, according to Angelique Brellenthin, PhD, of Iowa State University, Ames, and colleagues.

In a study presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting sponsored by the American Heart Association, the researchers reviewed information for 302,239 men and women who were enrolled in the U.K. Biobank, a population-based study of more than 500,000 individuals in the United Kingdom, between 2006 and 2010.

The study participants had no evidence of dementia at baseline, and completed questionnaires about family history and lifestyle. The questions included details about six healthy lifestyle behaviors: eating a healthy diet, engaging in at least 150 minutes of moderate to vigorous physical activity per week, sleeping 6-9 hours each night, drinking alcohol in moderation, not smoking, and maintaining a body mass index below the obese level (less than 30 kg/m²).

The researchers identified 1,698 participants (0.6%) who developed dementia over an average follow-up period of 8 years. Those with a family history (first-degree relative) of dementia had a 70% increased risk of dementia, compared with those who had no such family history.

Overall, individuals who engaged in all six healthy behaviors reduced their risk of dementia by about half, compared with those who engaged in two or fewer healthy behaviors. Engaging in three healthy behaviors reduced the risk of dementia by 30%, compared with engaging in two or fewer healthy behaviors, and this association held after controlling not only for family history of dementia, but also for other dementia risk factors such as age, sex, race, and education level, as well as high blood pressure, high cholesterol, and the presence of type 2 diabetes.

Similarly, among participants with a family history of dementia, those who engaged in three healthy lifestyle behaviors showed a 25%-35% reduction in dementia risk, compared with those who engaged in two or fewer healthy behaviors.

The study findings were limited by several factors including the inability to prove that lifestyle can cause or prevent dementia, only to show an association, the researchers noted. Also, the findings were limited by the reliance on self-reports, rather than genetic data, to confirm familial dementia.

However, the findings were strengthened by the large sample size, and the results suggest that a healthy lifestyle can impact cognitive health, and support the value of encouraging healthy behaviors in general, and especially among individuals with a family history of dementia, they said.
 

Small changes may promote prevention

The study is important now because, as the population ages, many individuals have a family member who has had dementia, said lead author Dr. Brellenthin, in an interview. “It’s important to understand how lifestyle behaviors affect the risk of dementia when it runs in families,” she said.

Dr. Brellenthin said she was surprised by some of the findings. “It was surprising to see that the risk of dementia was reduced with just three healthy behaviors [but was further reduced as you added more behaviors] compared to two or fewer behaviors. However, it was not surprising to see that these same lifestyle behaviors that tend to be good for the heart and body are also good for the brain.”

The evidence that following just three healthy behaviors can reduce the risk of dementia by 25%-35% for individuals with a familial history of dementia has clinical implications, Dr. Brellenthin said. “Many people are already following some of these behaviors like not smoking, so it might be possible to focus on adding just one more behavior, like getting enough sleep, and going from there.”

Commenting on the study, AHA President Mitchell S. V. Elkind, MD, said that the study “tells us that, yes, family history is important [in determining the risk of dementia], and much of that may be driven by genetic factors, but some of that impact can be mitigated or decreased by engaging in those important behaviors that we know are good to maintain brain health.

“The tricky thing, of course, is getting people to engage in these behaviors. That’s where a lot of work in the future will be: changing people’s behavior to become more healthy, and figuring out exactly which behaviors may be the easiest to engage in and be most likely to have public health impact,” added Dr. Elkind, professor of neurology and epidemiology at Columbia University and attending neurologist at New York–Presbyterian/Columbia University Irving Medical Center, New York.

The study received no outside funding, but the was research was conducted using the U.K. Biobank resources. The researchers had no financial conflicts to disclose.

Individuals at increased risk for dementia because of family history can reduce that risk by adopting healthy lifestyle behaviors, data from more than 300,000 adults aged 50-73 years suggest.

Having a parent or sibling with dementia can increase a person’s risk of developing dementia themselves by nearly 75%, compared with someone with no first-degree family history of dementia, according to Angelique Brellenthin, PhD, of Iowa State University, Ames, and colleagues.

In a study presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting sponsored by the American Heart Association, the researchers reviewed information for 302,239 men and women who were enrolled in the U.K. Biobank, a population-based study of more than 500,000 individuals in the United Kingdom, between 2006 and 2010.

The study participants had no evidence of dementia at baseline, and completed questionnaires about family history and lifestyle. The questions included details about six healthy lifestyle behaviors: eating a healthy diet, engaging in at least 150 minutes of moderate to vigorous physical activity per week, sleeping 6-9 hours each night, drinking alcohol in moderation, not smoking, and maintaining a body mass index below the obese level (less than 30 kg/m²).

The researchers identified 1,698 participants (0.6%) who developed dementia over an average follow-up period of 8 years. Those with a family history (first-degree relative) of dementia had a 70% increased risk of dementia, compared with those who had no such family history.

Overall, individuals who engaged in all six healthy behaviors reduced their risk of dementia by about half, compared with those who engaged in two or fewer healthy behaviors. Engaging in three healthy behaviors reduced the risk of dementia by 30%, compared with engaging in two or fewer healthy behaviors, and this association held after controlling not only for family history of dementia, but also for other dementia risk factors such as age, sex, race, and education level, as well as high blood pressure, high cholesterol, and the presence of type 2 diabetes.

Similarly, among participants with a family history of dementia, those who engaged in three healthy lifestyle behaviors showed a 25%-35% reduction in dementia risk, compared with those who engaged in two or fewer healthy behaviors.

The study findings were limited by several factors including the inability to prove that lifestyle can cause or prevent dementia, only to show an association, the researchers noted. Also, the findings were limited by the reliance on self-reports, rather than genetic data, to confirm familial dementia.

However, the findings were strengthened by the large sample size, and the results suggest that a healthy lifestyle can impact cognitive health, and support the value of encouraging healthy behaviors in general, and especially among individuals with a family history of dementia, they said.
 

Small changes may promote prevention

The study is important now because, as the population ages, many individuals have a family member who has had dementia, said lead author Dr. Brellenthin, in an interview. “It’s important to understand how lifestyle behaviors affect the risk of dementia when it runs in families,” she said.

Dr. Brellenthin said she was surprised by some of the findings. “It was surprising to see that the risk of dementia was reduced with just three healthy behaviors [but was further reduced as you added more behaviors] compared to two or fewer behaviors. However, it was not surprising to see that these same lifestyle behaviors that tend to be good for the heart and body are also good for the brain.”

The evidence that following just three healthy behaviors can reduce the risk of dementia by 25%-35% for individuals with a familial history of dementia has clinical implications, Dr. Brellenthin said. “Many people are already following some of these behaviors like not smoking, so it might be possible to focus on adding just one more behavior, like getting enough sleep, and going from there.”

Commenting on the study, AHA President Mitchell S. V. Elkind, MD, said that the study “tells us that, yes, family history is important [in determining the risk of dementia], and much of that may be driven by genetic factors, but some of that impact can be mitigated or decreased by engaging in those important behaviors that we know are good to maintain brain health.

“The tricky thing, of course, is getting people to engage in these behaviors. That’s where a lot of work in the future will be: changing people’s behavior to become more healthy, and figuring out exactly which behaviors may be the easiest to engage in and be most likely to have public health impact,” added Dr. Elkind, professor of neurology and epidemiology at Columbia University and attending neurologist at New York–Presbyterian/Columbia University Irving Medical Center, New York.

The study received no outside funding, but the was research was conducted using the U.K. Biobank resources. The researchers had no financial conflicts to disclose.

Individuals at increased risk for dementia because of family history can reduce that risk by adopting healthy lifestyle behaviors, data from more than 300,000 adults aged 50-73 years suggest.

Having a parent or sibling with dementia can increase a person’s risk of developing dementia themselves by nearly 75%, compared with someone with no first-degree family history of dementia, according to Angelique Brellenthin, PhD, of Iowa State University, Ames, and colleagues.

In a study presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting sponsored by the American Heart Association, the researchers reviewed information for 302,239 men and women who were enrolled in the U.K. Biobank, a population-based study of more than 500,000 individuals in the United Kingdom, between 2006 and 2010.

The study participants had no evidence of dementia at baseline, and completed questionnaires about family history and lifestyle. The questions included details about six healthy lifestyle behaviors: eating a healthy diet, engaging in at least 150 minutes of moderate to vigorous physical activity per week, sleeping 6-9 hours each night, drinking alcohol in moderation, not smoking, and maintaining a body mass index below the obese level (less than 30 kg/m²).

The researchers identified 1,698 participants (0.6%) who developed dementia over an average follow-up period of 8 years. Those with a family history (first-degree relative) of dementia had a 70% increased risk of dementia, compared with those who had no such family history.

Overall, individuals who engaged in all six healthy behaviors reduced their risk of dementia by about half, compared with those who engaged in two or fewer healthy behaviors. Engaging in three healthy behaviors reduced the risk of dementia by 30%, compared with engaging in two or fewer healthy behaviors, and this association held after controlling not only for family history of dementia, but also for other dementia risk factors such as age, sex, race, and education level, as well as high blood pressure, high cholesterol, and the presence of type 2 diabetes.

Similarly, among participants with a family history of dementia, those who engaged in three healthy lifestyle behaviors showed a 25%-35% reduction in dementia risk, compared with those who engaged in two or fewer healthy behaviors.

The study findings were limited by several factors including the inability to prove that lifestyle can cause or prevent dementia, only to show an association, the researchers noted. Also, the findings were limited by the reliance on self-reports, rather than genetic data, to confirm familial dementia.

However, the findings were strengthened by the large sample size, and the results suggest that a healthy lifestyle can impact cognitive health, and support the value of encouraging healthy behaviors in general, and especially among individuals with a family history of dementia, they said.
 

Small changes may promote prevention

The study is important now because, as the population ages, many individuals have a family member who has had dementia, said lead author Dr. Brellenthin, in an interview. “It’s important to understand how lifestyle behaviors affect the risk of dementia when it runs in families,” she said.

Dr. Brellenthin said she was surprised by some of the findings. “It was surprising to see that the risk of dementia was reduced with just three healthy behaviors [but was further reduced as you added more behaviors] compared to two or fewer behaviors. However, it was not surprising to see that these same lifestyle behaviors that tend to be good for the heart and body are also good for the brain.”

The evidence that following just three healthy behaviors can reduce the risk of dementia by 25%-35% for individuals with a familial history of dementia has clinical implications, Dr. Brellenthin said. “Many people are already following some of these behaviors like not smoking, so it might be possible to focus on adding just one more behavior, like getting enough sleep, and going from there.”

Commenting on the study, AHA President Mitchell S. V. Elkind, MD, said that the study “tells us that, yes, family history is important [in determining the risk of dementia], and much of that may be driven by genetic factors, but some of that impact can be mitigated or decreased by engaging in those important behaviors that we know are good to maintain brain health.

“The tricky thing, of course, is getting people to engage in these behaviors. That’s where a lot of work in the future will be: changing people’s behavior to become more healthy, and figuring out exactly which behaviors may be the easiest to engage in and be most likely to have public health impact,” added Dr. Elkind, professor of neurology and epidemiology at Columbia University and attending neurologist at New York–Presbyterian/Columbia University Irving Medical Center, New York.

The study received no outside funding, but the was research was conducted using the U.K. Biobank resources. The researchers had no financial conflicts to disclose.

Adding the novel immune checkpoint inhibitor relatlimab to the more established nivolumab (Opdivo) significantly extended the progression-free survival (PFS) of patients with previously untreated advanced melanoma in comparison with nivolumab alone in the phase 3 RELATIVITY-047 trial.

Both drugs are from Bristol-Myers Squibb, which funded the study.

“Our findings demonstrate that relatlimab plus nivolumab is a potential novel treatment option for this patient population,” said lead researcher Evan J. Lipson, MD, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore.

Relatlimab has a different mechanism of action from currently available immune checkpoint inhibitors, such as nivolumab and similar agents, which act as inhibitors of the programmed cell death protein–1 (PD-1) or programmed cell death–ligand-1 (PD-L1). In contrast, relatlimab acts as an antibody that targets lymphocyte-activation gene 3 (LAG-3), which inhibits T cells and thus helps cancer cells evade immune attack.

“This is the first phase 3 study to validate inhibition of the LAG-3 immune checkpoint as a therapeutic strategy for patients with cancer, and it establishes the LAG-3 pathway as the third immune checkpoint pathway in history, after CLTA-4 and PD-1, for which blockade appears to have clinical benefit,” Dr. Lipson said at a press briefing ahead of the annual meeting of the American Society of Clinical Oncology (ASCO), where this study will be presented (abstract 9503).

Commenting for ASCO, Julie R. Gralow, MD, chief medical officer and executive vice president, agreed that “these results provide validation of the LAG-3 immune checkpoint as a therapeutic target ... and they also support combination treatment with immunotherapies that act on different parts of the immune system.”

When Dr. Lipson was asked whether he would recommend the combination of relatlimab plus nivolumab as a first-line treatment for this patient population, he said that “for many patients,” the first-line treatment choice is made on a “case-by-case” basis.

“We are fortunate in melanoma that we have an ever-expanding list of seemingly effective options, and I think we’ll find at some point this will be added to that list,” he said. “Whether this is the first-line choice for any given patient really depends on a lot of factors,” he added.

Dr. Gralow added a note of caution. “The combination was clearly more toxic, and so I think there will be a lot of discussion” as to when it would be used and for which patients, she said.

In the absence of head-to-head comparisons, “I’m not sure that we have one answer” as to which treatment to choose, she added. With the ever-increasing number of options available in melanoma, the individual treatment choice is “getting more complicated,” she said.
 

Study details

The global RELATIVITY-047 study was conducted in 714 patients with previously untreated unresectable or metastatic melanoma. The participants were randomly assigned to receive either relatlimab plus nivolumab or nivolumab alone.

Dr. Lipson explained that the treatments were given as a fixed-dosed combination, meaning the preparation of relatlimab and nivolumab was given in the “same medication phial and administered as a single intravenous infusion in order to reduce preparation and infusion times and minimize the risk of administration errors.”

PFS, as determined on blinded independent central review, was significantly longer with the combination therapy than with nivolumab alone, at a median of 10.12 months vs. 4.63 months (hazard ratio, 0.75; P = .0055).

At 12 months, the PFS rate among patients given relatlimab plus nivolumab was 47.7%, versus 36.0% among those given nivolumab alone.

“This significant improvement meant that the study met its primary endpoint,” Dr. Lipson said, adding that the PFS benefit “appeared relatively early in the course of therapy.” The curves separated at 12 weeks, and benefit was “sustained” over the course of follow-up.

He added that the performance of nivolumab alone was “in the range” of that seen in previous studies, although he underlined that cross-trial comparison is difficult, given the differences in study design.

“In general, treatment-related adverse events” associated with the combination therapy were “manageable and reflected the safety profile that we typically see with immune checkpoint inhibitors,” he noted.

The results showed that 40.3% of patients who received the combination therapy experienced a grade 3-4 adverse event, compared with 33.4% of those given nivolumab alone. Grade 3-4 treatment-related adverse events leading to discontinuation occurred in 8.5% and 3.1% of patients, respectively.

Three treatment-related deaths occurred in the relatlimab and nivolumab arm. Two such deaths occurred in the nivolumab-alone group.

The study was funded by Bristol Myers Squibb. Dr. Lipson has relationships with Array BioPharma, Bristol Myers Squibb, EMD Serono, Genentech, Macrogenics, Merck, Millennium, Novartis, Sanofi/Regeneron, and Sysmex (inst). Dr. Gralow has relationships with AstraZeneca, Genentech, Sandoz, and Immunomedics.

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

Adding the novel immune checkpoint inhibitor relatlimab to the more established nivolumab (Opdivo) significantly extended the progression-free survival (PFS) of patients with previously untreated advanced melanoma in comparison with nivolumab alone in the phase 3 RELATIVITY-047 trial.

Both drugs are from Bristol-Myers Squibb, which funded the study.

“Our findings demonstrate that relatlimab plus nivolumab is a potential novel treatment option for this patient population,” said lead researcher Evan J. Lipson, MD, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore.

Relatlimab has a different mechanism of action from currently available immune checkpoint inhibitors, such as nivolumab and similar agents, which act as inhibitors of the programmed cell death protein–1 (PD-1) or programmed cell death–ligand-1 (PD-L1). In contrast, relatlimab acts as an antibody that targets lymphocyte-activation gene 3 (LAG-3), which inhibits T cells and thus helps cancer cells evade immune attack.

“This is the first phase 3 study to validate inhibition of the LAG-3 immune checkpoint as a therapeutic strategy for patients with cancer, and it establishes the LAG-3 pathway as the third immune checkpoint pathway in history, after CLTA-4 and PD-1, for which blockade appears to have clinical benefit,” Dr. Lipson said at a press briefing ahead of the annual meeting of the American Society of Clinical Oncology (ASCO), where this study will be presented (abstract 9503).

Commenting for ASCO, Julie R. Gralow, MD, chief medical officer and executive vice president, agreed that “these results provide validation of the LAG-3 immune checkpoint as a therapeutic target ... and they also support combination treatment with immunotherapies that act on different parts of the immune system.”

When Dr. Lipson was asked whether he would recommend the combination of relatlimab plus nivolumab as a first-line treatment for this patient population, he said that “for many patients,” the first-line treatment choice is made on a “case-by-case” basis.

“We are fortunate in melanoma that we have an ever-expanding list of seemingly effective options, and I think we’ll find at some point this will be added to that list,” he said. “Whether this is the first-line choice for any given patient really depends on a lot of factors,” he added.

Dr. Gralow added a note of caution. “The combination was clearly more toxic, and so I think there will be a lot of discussion” as to when it would be used and for which patients, she said.

In the absence of head-to-head comparisons, “I’m not sure that we have one answer” as to which treatment to choose, she added. With the ever-increasing number of options available in melanoma, the individual treatment choice is “getting more complicated,” she said.
 

Study details

The global RELATIVITY-047 study was conducted in 714 patients with previously untreated unresectable or metastatic melanoma. The participants were randomly assigned to receive either relatlimab plus nivolumab or nivolumab alone.

Dr. Lipson explained that the treatments were given as a fixed-dosed combination, meaning the preparation of relatlimab and nivolumab was given in the “same medication phial and administered as a single intravenous infusion in order to reduce preparation and infusion times and minimize the risk of administration errors.”

PFS, as determined on blinded independent central review, was significantly longer with the combination therapy than with nivolumab alone, at a median of 10.12 months vs. 4.63 months (hazard ratio, 0.75; P = .0055).

At 12 months, the PFS rate among patients given relatlimab plus nivolumab was 47.7%, versus 36.0% among those given nivolumab alone.

“This significant improvement meant that the study met its primary endpoint,” Dr. Lipson said, adding that the PFS benefit “appeared relatively early in the course of therapy.” The curves separated at 12 weeks, and benefit was “sustained” over the course of follow-up.

He added that the performance of nivolumab alone was “in the range” of that seen in previous studies, although he underlined that cross-trial comparison is difficult, given the differences in study design.

“In general, treatment-related adverse events” associated with the combination therapy were “manageable and reflected the safety profile that we typically see with immune checkpoint inhibitors,” he noted.

The results showed that 40.3% of patients who received the combination therapy experienced a grade 3-4 adverse event, compared with 33.4% of those given nivolumab alone. Grade 3-4 treatment-related adverse events leading to discontinuation occurred in 8.5% and 3.1% of patients, respectively.

Three treatment-related deaths occurred in the relatlimab and nivolumab arm. Two such deaths occurred in the nivolumab-alone group.

The study was funded by Bristol Myers Squibb. Dr. Lipson has relationships with Array BioPharma, Bristol Myers Squibb, EMD Serono, Genentech, Macrogenics, Merck, Millennium, Novartis, Sanofi/Regeneron, and Sysmex (inst). Dr. Gralow has relationships with AstraZeneca, Genentech, Sandoz, and Immunomedics.

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

Adding the novel immune checkpoint inhibitor relatlimab to the more established nivolumab (Opdivo) significantly extended the progression-free survival (PFS) of patients with previously untreated advanced melanoma in comparison with nivolumab alone in the phase 3 RELATIVITY-047 trial.

Both drugs are from Bristol-Myers Squibb, which funded the study.

“Our findings demonstrate that relatlimab plus nivolumab is a potential novel treatment option for this patient population,” said lead researcher Evan J. Lipson, MD, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore.

Relatlimab has a different mechanism of action from currently available immune checkpoint inhibitors, such as nivolumab and similar agents, which act as inhibitors of the programmed cell death protein–1 (PD-1) or programmed cell death–ligand-1 (PD-L1). In contrast, relatlimab acts as an antibody that targets lymphocyte-activation gene 3 (LAG-3), which inhibits T cells and thus helps cancer cells evade immune attack.

“This is the first phase 3 study to validate inhibition of the LAG-3 immune checkpoint as a therapeutic strategy for patients with cancer, and it establishes the LAG-3 pathway as the third immune checkpoint pathway in history, after CLTA-4 and PD-1, for which blockade appears to have clinical benefit,” Dr. Lipson said at a press briefing ahead of the annual meeting of the American Society of Clinical Oncology (ASCO), where this study will be presented (abstract 9503).

Commenting for ASCO, Julie R. Gralow, MD, chief medical officer and executive vice president, agreed that “these results provide validation of the LAG-3 immune checkpoint as a therapeutic target ... and they also support combination treatment with immunotherapies that act on different parts of the immune system.”

When Dr. Lipson was asked whether he would recommend the combination of relatlimab plus nivolumab as a first-line treatment for this patient population, he said that “for many patients,” the first-line treatment choice is made on a “case-by-case” basis.

“We are fortunate in melanoma that we have an ever-expanding list of seemingly effective options, and I think we’ll find at some point this will be added to that list,” he said. “Whether this is the first-line choice for any given patient really depends on a lot of factors,” he added.

Dr. Gralow added a note of caution. “The combination was clearly more toxic, and so I think there will be a lot of discussion” as to when it would be used and for which patients, she said.

In the absence of head-to-head comparisons, “I’m not sure that we have one answer” as to which treatment to choose, she added. With the ever-increasing number of options available in melanoma, the individual treatment choice is “getting more complicated,” she said.
 

Study details

The global RELATIVITY-047 study was conducted in 714 patients with previously untreated unresectable or metastatic melanoma. The participants were randomly assigned to receive either relatlimab plus nivolumab or nivolumab alone.

Dr. Lipson explained that the treatments were given as a fixed-dosed combination, meaning the preparation of relatlimab and nivolumab was given in the “same medication phial and administered as a single intravenous infusion in order to reduce preparation and infusion times and minimize the risk of administration errors.”

PFS, as determined on blinded independent central review, was significantly longer with the combination therapy than with nivolumab alone, at a median of 10.12 months vs. 4.63 months (hazard ratio, 0.75; P = .0055).

At 12 months, the PFS rate among patients given relatlimab plus nivolumab was 47.7%, versus 36.0% among those given nivolumab alone.

“This significant improvement meant that the study met its primary endpoint,” Dr. Lipson said, adding that the PFS benefit “appeared relatively early in the course of therapy.” The curves separated at 12 weeks, and benefit was “sustained” over the course of follow-up.

He added that the performance of nivolumab alone was “in the range” of that seen in previous studies, although he underlined that cross-trial comparison is difficult, given the differences in study design.

“In general, treatment-related adverse events” associated with the combination therapy were “manageable and reflected the safety profile that we typically see with immune checkpoint inhibitors,” he noted.

The results showed that 40.3% of patients who received the combination therapy experienced a grade 3-4 adverse event, compared with 33.4% of those given nivolumab alone. Grade 3-4 treatment-related adverse events leading to discontinuation occurred in 8.5% and 3.1% of patients, respectively.

Three treatment-related deaths occurred in the relatlimab and nivolumab arm. Two such deaths occurred in the nivolumab-alone group.

The study was funded by Bristol Myers Squibb. Dr. Lipson has relationships with Array BioPharma, Bristol Myers Squibb, EMD Serono, Genentech, Macrogenics, Merck, Millennium, Novartis, Sanofi/Regeneron, and Sysmex (inst). Dr. Gralow has relationships with AstraZeneca, Genentech, Sandoz, and Immunomedics.

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

Cervical cancer incidence in the United States decreased by about 1% per year from 2001 to 2017, but at the same time there was an increase in the incidence of other human papillomavirus (HPV)–related cancers, a new study reveals.

Over the same period, there was an overall 1.3% annual increase in oropharyngeal, anal, rectal, and vulvar cancers in women, and a 2.3% annual increase in these cancers in men.

HPV is associated with more than 90% of cervical cancers and between 60% and 75% of oropharyngeal, vulvar, vaginal, and penile cancer in the United States, the researchers noted.

Oropharyngeal cancer incidence increased by 2.3% overall, with a 2.7% increase in men and a 0.77% increase in women. The incidence of this cancer was nearly fivefold greater in men at 8.89 per 100,000 population versus 1.68 per 100,000 population for women, the study found.

In addition, among women over age 50 years, anal and rectal cancer incidence increased by 3.5% per year; at the same time, cervical cancer incidence decreased 1.5% per year.

The increase in the incidence of oropharyngeal cancer and in anal and rectal cancers is expected to continue, the authors said.

The data showing these new trends come from an analysis of 657,317 individuals obtained from the U.S. Cancer Statistics program, conducted by Cheng-I Liao, MD, of Kaohsiung (Taiwan) Veterans Hospital and colleagues.

The study was highlighted at a press briefing ahead of the annual meeting of the American Society of Clinical Oncology, where the study will be presented June 6.

These incidence trends may reflect the availability of clear guidelines for screening and vaccination for the prevention of HPV-related cervical cancer – and the dearth of guidelines and standardized screening and vaccination for the other HPV-related cancers, the authors said.

The team also found cervical cancer accounted for 52% of all HPV-related cancers during the study period. The decrease in the incidence of cervical cancer over time was greater among women aged 20-24 (4.6% per year), compared with those aged 25-29 years (1.6%) and 30-34 years (1.1%),

Dr. Liao speculated that this age-based difference suggests a potential effect of HPV vaccination, greater vaccine acceptance among younger women, and clear guidelines for screening and vaccination.

However, an expert approached for comment was not so sure. It is likely too soon to give HPV vaccination too much credit for lower cervical cancer rates, said Jennifer Young Pierce, MD, MPH, a gynecologic oncologist at the Mitchell Cancer Institute, University of South Alabama, Mobile.

The continued rise in HPV-related cancers other than cervical cancers supports the point that screening – rather than vaccination – accounts for much of the decline observed in cervical cancer incidence, Dr. Pierce said in an interview.

Vaccination in men lags behind that of women, and there is a lack of good screening methods for head and neck cancers, she explained.

“When we have both vaccination and screening in these other cancers at high rates, we’re going to see significant declines in those cancers also,” she said.

“I’m very excited by the data but I do not believe it is related to vaccination as a method of prevention,” said Dr. Pierce, a professor of interdisciplinary clinical oncology who has been involved in numerous HPV vaccine–related studies and initiatives to improve vaccine uptake since its approval in 2006.
 

HPV vaccination

The HPV vaccine was first approved for preventing HPV-related cervical cancer in 2006 with an indication for girls and women aged 9-26 years. The vaccine indication was expanded in 2011 to include boys aged 11-12 years and is now approved for those up to age 45 years.

However, neither standardized screening nor HPV vaccination is currently recommended for any HPV-related cancer other than cervical cancer, Dr. Liao said.

Vaccination during much of the current study time frame (2001-2017) didn’t apply to most of the people who got cancer, Dr. Pierce explained in an interview, noting that the vaccinated individuals “still aren’t old enough to be part of the group we’re talking about.”

Rather, the increased use of HPV screening along with Pap testing for cervical cancer was becoming much more widespread at the time and was likely picking up more precancerous lesions – and thereby helping to decrease cervical cancer incidence in women in their 40s, 50s, 60s, and 70s, she said.

Dr. Pierce does, however, credit the vaccine movement for improving awareness of HPV risk.

“It has done a great job of educating the population about the dangers of these cancers ... and that there’s more we can do to prevent them,” she said.

Like Dr. Liao, she stressed the need for research focused on finding more effective screening modalities and on vaccine efficacy.

Also commenting on the study, ASCO president Lori J. Pierce, MD, a radiation oncologist, professor, and vice provost for academic and faculty affairs at the University of Michigan, Ann Arbor, said the findings underscore the need for ongoing exploration of potential strategies such as HPV screening for high-risk populations.

“We can pick out higher risk populations so it would make sense to do a screen,” she said.

“Clearly, this study shows that we still have a great deal of work to do in order to reverse the increasing incidence rates of other HPV-related cancers,” she added in a press statement.

In an interview prior to the press conference, Dr. Pierce said in an interview that the findings are important because the outcome “opens all of our eyes into the trends of HPV-related cancers in the United States.

“This is something that hasn’t been studied well over time,” she added, noting that, where guidelines do exist for HPV-related cancers other than cervical cancer, they are inconsistent.

Further, it is possible that the vaccine will “cover a significant portion of the etiologic viruses that cause these cancers,” thereby helping to prevent the other HPV-related cancers.

For that reason, additional research and strategies for overcoming vaccine hesitancy, increasing overall vaccination rates, and for developing consistent guidelines are needed.

“I think there needs to be further resources and research to address the lack of screening for these other HPV-related cancers and we need to have consistent vaccination guidelines, because these cancers are preventable,” she said

Dr. Liao and Dr. Pierce disclosed no relevant financial relationships.

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

Cervical cancer incidence in the United States decreased by about 1% per year from 2001 to 2017, but at the same time there was an increase in the incidence of other human papillomavirus (HPV)–related cancers, a new study reveals.

Over the same period, there was an overall 1.3% annual increase in oropharyngeal, anal, rectal, and vulvar cancers in women, and a 2.3% annual increase in these cancers in men.

HPV is associated with more than 90% of cervical cancers and between 60% and 75% of oropharyngeal, vulvar, vaginal, and penile cancer in the United States, the researchers noted.

Oropharyngeal cancer incidence increased by 2.3% overall, with a 2.7% increase in men and a 0.77% increase in women. The incidence of this cancer was nearly fivefold greater in men at 8.89 per 100,000 population versus 1.68 per 100,000 population for women, the study found.

In addition, among women over age 50 years, anal and rectal cancer incidence increased by 3.5% per year; at the same time, cervical cancer incidence decreased 1.5% per year.

The increase in the incidence of oropharyngeal cancer and in anal and rectal cancers is expected to continue, the authors said.

The data showing these new trends come from an analysis of 657,317 individuals obtained from the U.S. Cancer Statistics program, conducted by Cheng-I Liao, MD, of Kaohsiung (Taiwan) Veterans Hospital and colleagues.

The study was highlighted at a press briefing ahead of the annual meeting of the American Society of Clinical Oncology, where the study will be presented June 6.

These incidence trends may reflect the availability of clear guidelines for screening and vaccination for the prevention of HPV-related cervical cancer – and the dearth of guidelines and standardized screening and vaccination for the other HPV-related cancers, the authors said.

The team also found cervical cancer accounted for 52% of all HPV-related cancers during the study period. The decrease in the incidence of cervical cancer over time was greater among women aged 20-24 (4.6% per year), compared with those aged 25-29 years (1.6%) and 30-34 years (1.1%),

Dr. Liao speculated that this age-based difference suggests a potential effect of HPV vaccination, greater vaccine acceptance among younger women, and clear guidelines for screening and vaccination.

However, an expert approached for comment was not so sure. It is likely too soon to give HPV vaccination too much credit for lower cervical cancer rates, said Jennifer Young Pierce, MD, MPH, a gynecologic oncologist at the Mitchell Cancer Institute, University of South Alabama, Mobile.

The continued rise in HPV-related cancers other than cervical cancers supports the point that screening – rather than vaccination – accounts for much of the decline observed in cervical cancer incidence, Dr. Pierce said in an interview.

Vaccination in men lags behind that of women, and there is a lack of good screening methods for head and neck cancers, she explained.

“When we have both vaccination and screening in these other cancers at high rates, we’re going to see significant declines in those cancers also,” she said.

“I’m very excited by the data but I do not believe it is related to vaccination as a method of prevention,” said Dr. Pierce, a professor of interdisciplinary clinical oncology who has been involved in numerous HPV vaccine–related studies and initiatives to improve vaccine uptake since its approval in 2006.
 

HPV vaccination

The HPV vaccine was first approved for preventing HPV-related cervical cancer in 2006 with an indication for girls and women aged 9-26 years. The vaccine indication was expanded in 2011 to include boys aged 11-12 years and is now approved for those up to age 45 years.

However, neither standardized screening nor HPV vaccination is currently recommended for any HPV-related cancer other than cervical cancer, Dr. Liao said.

Vaccination during much of the current study time frame (2001-2017) didn’t apply to most of the people who got cancer, Dr. Pierce explained in an interview, noting that the vaccinated individuals “still aren’t old enough to be part of the group we’re talking about.”

Rather, the increased use of HPV screening along with Pap testing for cervical cancer was becoming much more widespread at the time and was likely picking up more precancerous lesions – and thereby helping to decrease cervical cancer incidence in women in their 40s, 50s, 60s, and 70s, she said.

Dr. Pierce does, however, credit the vaccine movement for improving awareness of HPV risk.

“It has done a great job of educating the population about the dangers of these cancers ... and that there’s more we can do to prevent them,” she said.

Like Dr. Liao, she stressed the need for research focused on finding more effective screening modalities and on vaccine efficacy.

Also commenting on the study, ASCO president Lori J. Pierce, MD, a radiation oncologist, professor, and vice provost for academic and faculty affairs at the University of Michigan, Ann Arbor, said the findings underscore the need for ongoing exploration of potential strategies such as HPV screening for high-risk populations.

“We can pick out higher risk populations so it would make sense to do a screen,” she said.

“Clearly, this study shows that we still have a great deal of work to do in order to reverse the increasing incidence rates of other HPV-related cancers,” she added in a press statement.

In an interview prior to the press conference, Dr. Pierce said in an interview that the findings are important because the outcome “opens all of our eyes into the trends of HPV-related cancers in the United States.

“This is something that hasn’t been studied well over time,” she added, noting that, where guidelines do exist for HPV-related cancers other than cervical cancer, they are inconsistent.

Further, it is possible that the vaccine will “cover a significant portion of the etiologic viruses that cause these cancers,” thereby helping to prevent the other HPV-related cancers.

For that reason, additional research and strategies for overcoming vaccine hesitancy, increasing overall vaccination rates, and for developing consistent guidelines are needed.

“I think there needs to be further resources and research to address the lack of screening for these other HPV-related cancers and we need to have consistent vaccination guidelines, because these cancers are preventable,” she said

Dr. Liao and Dr. Pierce disclosed no relevant financial relationships.

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

Cervical cancer incidence in the United States decreased by about 1% per year from 2001 to 2017, but at the same time there was an increase in the incidence of other human papillomavirus (HPV)–related cancers, a new study reveals.

Over the same period, there was an overall 1.3% annual increase in oropharyngeal, anal, rectal, and vulvar cancers in women, and a 2.3% annual increase in these cancers in men.

HPV is associated with more than 90% of cervical cancers and between 60% and 75% of oropharyngeal, vulvar, vaginal, and penile cancer in the United States, the researchers noted.

Oropharyngeal cancer incidence increased by 2.3% overall, with a 2.7% increase in men and a 0.77% increase in women. The incidence of this cancer was nearly fivefold greater in men at 8.89 per 100,000 population versus 1.68 per 100,000 population for women, the study found.

In addition, among women over age 50 years, anal and rectal cancer incidence increased by 3.5% per year; at the same time, cervical cancer incidence decreased 1.5% per year.

The increase in the incidence of oropharyngeal cancer and in anal and rectal cancers is expected to continue, the authors said.

The data showing these new trends come from an analysis of 657,317 individuals obtained from the U.S. Cancer Statistics program, conducted by Cheng-I Liao, MD, of Kaohsiung (Taiwan) Veterans Hospital and colleagues.

The study was highlighted at a press briefing ahead of the annual meeting of the American Society of Clinical Oncology, where the study will be presented June 6.

These incidence trends may reflect the availability of clear guidelines for screening and vaccination for the prevention of HPV-related cervical cancer – and the dearth of guidelines and standardized screening and vaccination for the other HPV-related cancers, the authors said.

The team also found cervical cancer accounted for 52% of all HPV-related cancers during the study period. The decrease in the incidence of cervical cancer over time was greater among women aged 20-24 (4.6% per year), compared with those aged 25-29 years (1.6%) and 30-34 years (1.1%),

Dr. Liao speculated that this age-based difference suggests a potential effect of HPV vaccination, greater vaccine acceptance among younger women, and clear guidelines for screening and vaccination.

However, an expert approached for comment was not so sure. It is likely too soon to give HPV vaccination too much credit for lower cervical cancer rates, said Jennifer Young Pierce, MD, MPH, a gynecologic oncologist at the Mitchell Cancer Institute, University of South Alabama, Mobile.

The continued rise in HPV-related cancers other than cervical cancers supports the point that screening – rather than vaccination – accounts for much of the decline observed in cervical cancer incidence, Dr. Pierce said in an interview.

Vaccination in men lags behind that of women, and there is a lack of good screening methods for head and neck cancers, she explained.

“When we have both vaccination and screening in these other cancers at high rates, we’re going to see significant declines in those cancers also,” she said.

“I’m very excited by the data but I do not believe it is related to vaccination as a method of prevention,” said Dr. Pierce, a professor of interdisciplinary clinical oncology who has been involved in numerous HPV vaccine–related studies and initiatives to improve vaccine uptake since its approval in 2006.
 

HPV vaccination

The HPV vaccine was first approved for preventing HPV-related cervical cancer in 2006 with an indication for girls and women aged 9-26 years. The vaccine indication was expanded in 2011 to include boys aged 11-12 years and is now approved for those up to age 45 years.

However, neither standardized screening nor HPV vaccination is currently recommended for any HPV-related cancer other than cervical cancer, Dr. Liao said.

Vaccination during much of the current study time frame (2001-2017) didn’t apply to most of the people who got cancer, Dr. Pierce explained in an interview, noting that the vaccinated individuals “still aren’t old enough to be part of the group we’re talking about.”

Rather, the increased use of HPV screening along with Pap testing for cervical cancer was becoming much more widespread at the time and was likely picking up more precancerous lesions – and thereby helping to decrease cervical cancer incidence in women in their 40s, 50s, 60s, and 70s, she said.

Dr. Pierce does, however, credit the vaccine movement for improving awareness of HPV risk.

“It has done a great job of educating the population about the dangers of these cancers ... and that there’s more we can do to prevent them,” she said.

Like Dr. Liao, she stressed the need for research focused on finding more effective screening modalities and on vaccine efficacy.

Also commenting on the study, ASCO president Lori J. Pierce, MD, a radiation oncologist, professor, and vice provost for academic and faculty affairs at the University of Michigan, Ann Arbor, said the findings underscore the need for ongoing exploration of potential strategies such as HPV screening for high-risk populations.

“We can pick out higher risk populations so it would make sense to do a screen,” she said.

“Clearly, this study shows that we still have a great deal of work to do in order to reverse the increasing incidence rates of other HPV-related cancers,” she added in a press statement.

In an interview prior to the press conference, Dr. Pierce said in an interview that the findings are important because the outcome “opens all of our eyes into the trends of HPV-related cancers in the United States.

“This is something that hasn’t been studied well over time,” she added, noting that, where guidelines do exist for HPV-related cancers other than cervical cancer, they are inconsistent.

Further, it is possible that the vaccine will “cover a significant portion of the etiologic viruses that cause these cancers,” thereby helping to prevent the other HPV-related cancers.

For that reason, additional research and strategies for overcoming vaccine hesitancy, increasing overall vaccination rates, and for developing consistent guidelines are needed.

“I think there needs to be further resources and research to address the lack of screening for these other HPV-related cancers and we need to have consistent vaccination guidelines, because these cancers are preventable,” she said

Dr. Liao and Dr. Pierce disclosed no relevant financial relationships.

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

A new analysis from the TWILIGHT study has shown that, in the high-risk population undergoing percutaneous coronary intervention (PCI) enrolled in the study, the benefits of early aspirin withdrawal and continuation on ticagrelor monotherapy were similar in women and men.

But there were some interesting observations in the analysis suggesting possible additional benefits of this strategy for women.

“These data support the use of ticagrelor monotherapy in women and men, and importantly show that the absolute risk reduction of bleeding was higher in women, as their bleeding rates were higher,” senior author Roxana Mehran, MD, the Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, said in an interview.

“These data also support the need for prospective dual antiplatelet therapy deescalation studies in women,” Dr. Mehran added.

The main results of the TWILIGHT study showed that after a short period of dual antiplatelet therapy, a strategy of ticagrelor monotherapy, compared with continued dual therapy led to reduced bleeding without an increase in ischemic events among patients at high risk for bleeding or ischemic events after PCI.

The new gender-based analysis was presented by Birgit Vogel, MD, on May 15 at the annual scientific sessions of the American College of Cardiology. It was also published online in JAMA Cardiology to coincide with the ACC presentation.

Dr. Vogel, also from Wiener Cardiovascular Institute, explained that the current analysis was undertaken to investigate whether the TWILIGHT results varied in relation to sex, given that women are believed to have an increased risk for bleeding after PCI, compared with men.

“The current analysis showed that, while women did have a higher bleeding risk, compared to men, this was no longer significant after adjustment for baseline characteristics; and ischemic events were similar between the two sexes,” she reported.

“Results showed that withdrawing aspirin while continuing ticagrelor after 3 months of dual antiplatelet therapy was associated with a reduction in bleeding and preserved ischemic benefits in both women and men,” she added.

The TWILIGHT trial randomized 7,119 patients at high risk of ischemic or bleeding events who had undergone successful PCI with at least one drug-eluting stent and had completed 3 months of dual antiplatelet therapy to aspirin or placebo for an additional 12 months plus open-label ticagrelor.

The main results showed that the primary endpoint of Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding at 1 year was almost halved with ticagrelor monotherapy, occurring in 4% of these patients, compared with 7.1% of the ticagrelor/aspirin group (hazard ratio, 0.56). Ischemic events were similar in the two groups.

The current analysis focused on whether these effects varied in relation to sex.

Dr. Vogel noted that women made up 23.9% of the study population, were older than the men, and were more likely to have diabetes, chronic kidney disease, anemia and hypertension, while the men were more likely to be current smokers. Men had a higher incidence of coronary heart disease history, while women were more likely to have an ACS indication for PCI.

Unadjusted results showed a higher rate of BARC 2, 3, or 5 bleeding at 1 year in women (6.8%) versus men (5.2%), giving an HR of 1.32 (95% CI, 1.06-1.64).

But after adjustment for baseline characteristics, this became nonsignificant (HR, 1.20; 95% CI, 0.95-1.52).

Dr. Vogel pointed out that the most severe type of bleeding (BARC 3 and 5) was not attenuated as much by adjustment for baseline characteristics, with the HR reducing from 1.57 to 1.49.

The ischemic endpoint of death/stroke or MI was similar in men (4.0%) and women (3.5%), and this did not change after adjustment for baseline characteristics.

In terms of the two treatment groups, BARC 2, 3, or 5 bleeding was reduced to a similar extent with ticagrelor monotherapy in both men and women. This endpoint decreased from 8.6% in women on dual-antiplatelet therapy to 5.0% in women on ticagrelor alone (adjusted HR, 0.62) and from 6.6% to 3.7% in men (aHR, 0.57). But she noted that the absolute risk reduction in bleeding was greater in women (3.6%) versus men (2.9%).

“If we have a relative risk reduction in bleeding with early withdrawal of aspirin that is similar between the sexes but an overall higher risk of bleeding in women, that results in a greater absolute risk reduction,” Dr. Vogel commented.

The primary ischemic endpoint of death/MI/stroke was not increased in the ticagrelor group vs the dual antiplatelet group in either men (aHR, 1.06) or women (aHR, 1.04).
 

Greater reduction in mortality in women?

However, Dr. Vogel reported that there was a suggestion of a greater reduction in all-cause mortality with ticagrelor monotherapy in women versus men. “We found a significant interaction for treatment effect and sex for all-cause mortality, a prespecified endpoint, which was significantly lower in women treated with ticagrelor monotherapy, compared to dual antiplatelet therapy, but this was not the case in men.”

However, this observation was based on few events and should not be considered definitive, she added.

Dr. Vogel noted that the analysis had the limitations of the study not being powered to show differences in men versus women, and the results are only applicable to the population studied who were at high risk of bleeding post PCI.

Commenting on the study at the ACC session, Jacqueline Tamis-Holland, MD, associate professor of medicine at the Icahn School of Medicine at Mount Sinai, described the presentation as “very interesting.”

“We know that women notoriously have higher bleeding risk than men, but this particular study did not show a difference in bleeding risk after adjusting for other confounding variables,” she said.

“In fact, one would think that the relative benefit of a treatment designed to decrease bleeding would be more favorable to women, but this analysis didn’t show that,” she added.

Dr. Vogel replied that the HR of the most serious type of bleeding (BARC 3 and 5) in women versus men was only reduced minimally after adjustment for baseline characteristics, “which still makes us think that there are additional factors that might be important and contribute to an increased risk for bleeding and especially more serous types of bleeding in women.”

She pointed out that, while there was a similar risk reduction in bleeding in women and men, there was a potential mortality benefit in women. “The question is whether this mortality benefit is due to reduced bleeding that might be greater in women than men, and the reality is we don’t have a lot of data on that.”

Dr. Vogel added: “We know about the relationship between bleeding and mortality very well but the impact of sex on this is really not well investigated. It would be worth investigating this further to come up with bleeding reduction strategies for women because this is a really important issue.”

This work was supported by an investigator-initiated grant from AstraZeneca. Dr. Mehran reported grants and personal fees (paid to the institution) from Abbott, Abiomed, Bayer, Beth Israel Deaconess, Bristol-Myers Squibb, Chiesi, Concept Medical Research, Medtronic, Novartis and DSI Research; grants from Applied Therapeutics, AstraZeneca, Cerecor, CSL Behring, OrbusNeich, and Zoll; personal fees from Boston Scientific, California Institute for Regenerative Medicine, Cine-Med Research, Janssen Scientific Affairs, ACC, and WebMD; personal fees paid to the institution from CardiaWave, Duke University, and Idorsia Pharmaceuticals; serving as a consultant or committee or advisory board member for Society for Cardiovascular Angiography and Interventions, the American Medical Association, and Regeneron Pharmaceuticals; and owning stock in ControlRad, Elixir Medical, and STEL outside the submitted work. Dr. Vogel disclosed no relevant financial relationships.

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

A new analysis from the TWILIGHT study has shown that, in the high-risk population undergoing percutaneous coronary intervention (PCI) enrolled in the study, the benefits of early aspirin withdrawal and continuation on ticagrelor monotherapy were similar in women and men.

But there were some interesting observations in the analysis suggesting possible additional benefits of this strategy for women.

“These data support the use of ticagrelor monotherapy in women and men, and importantly show that the absolute risk reduction of bleeding was higher in women, as their bleeding rates were higher,” senior author Roxana Mehran, MD, the Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, said in an interview.

“These data also support the need for prospective dual antiplatelet therapy deescalation studies in women,” Dr. Mehran added.

The main results of the TWILIGHT study showed that after a short period of dual antiplatelet therapy, a strategy of ticagrelor monotherapy, compared with continued dual therapy led to reduced bleeding without an increase in ischemic events among patients at high risk for bleeding or ischemic events after PCI.

The new gender-based analysis was presented by Birgit Vogel, MD, on May 15 at the annual scientific sessions of the American College of Cardiology. It was also published online in JAMA Cardiology to coincide with the ACC presentation.

Dr. Vogel, also from Wiener Cardiovascular Institute, explained that the current analysis was undertaken to investigate whether the TWILIGHT results varied in relation to sex, given that women are believed to have an increased risk for bleeding after PCI, compared with men.

“The current analysis showed that, while women did have a higher bleeding risk, compared to men, this was no longer significant after adjustment for baseline characteristics; and ischemic events were similar between the two sexes,” she reported.

“Results showed that withdrawing aspirin while continuing ticagrelor after 3 months of dual antiplatelet therapy was associated with a reduction in bleeding and preserved ischemic benefits in both women and men,” she added.

The TWILIGHT trial randomized 7,119 patients at high risk of ischemic or bleeding events who had undergone successful PCI with at least one drug-eluting stent and had completed 3 months of dual antiplatelet therapy to aspirin or placebo for an additional 12 months plus open-label ticagrelor.

The main results showed that the primary endpoint of Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding at 1 year was almost halved with ticagrelor monotherapy, occurring in 4% of these patients, compared with 7.1% of the ticagrelor/aspirin group (hazard ratio, 0.56). Ischemic events were similar in the two groups.

The current analysis focused on whether these effects varied in relation to sex.

Dr. Vogel noted that women made up 23.9% of the study population, were older than the men, and were more likely to have diabetes, chronic kidney disease, anemia and hypertension, while the men were more likely to be current smokers. Men had a higher incidence of coronary heart disease history, while women were more likely to have an ACS indication for PCI.

Unadjusted results showed a higher rate of BARC 2, 3, or 5 bleeding at 1 year in women (6.8%) versus men (5.2%), giving an HR of 1.32 (95% CI, 1.06-1.64).

But after adjustment for baseline characteristics, this became nonsignificant (HR, 1.20; 95% CI, 0.95-1.52).

Dr. Vogel pointed out that the most severe type of bleeding (BARC 3 and 5) was not attenuated as much by adjustment for baseline characteristics, with the HR reducing from 1.57 to 1.49.

The ischemic endpoint of death/stroke or MI was similar in men (4.0%) and women (3.5%), and this did not change after adjustment for baseline characteristics.

In terms of the two treatment groups, BARC 2, 3, or 5 bleeding was reduced to a similar extent with ticagrelor monotherapy in both men and women. This endpoint decreased from 8.6% in women on dual-antiplatelet therapy to 5.0% in women on ticagrelor alone (adjusted HR, 0.62) and from 6.6% to 3.7% in men (aHR, 0.57). But she noted that the absolute risk reduction in bleeding was greater in women (3.6%) versus men (2.9%).

“If we have a relative risk reduction in bleeding with early withdrawal of aspirin that is similar between the sexes but an overall higher risk of bleeding in women, that results in a greater absolute risk reduction,” Dr. Vogel commented.

The primary ischemic endpoint of death/MI/stroke was not increased in the ticagrelor group vs the dual antiplatelet group in either men (aHR, 1.06) or women (aHR, 1.04).
 

Greater reduction in mortality in women?

However, Dr. Vogel reported that there was a suggestion of a greater reduction in all-cause mortality with ticagrelor monotherapy in women versus men. “We found a significant interaction for treatment effect and sex for all-cause mortality, a prespecified endpoint, which was significantly lower in women treated with ticagrelor monotherapy, compared to dual antiplatelet therapy, but this was not the case in men.”

However, this observation was based on few events and should not be considered definitive, she added.

Dr. Vogel noted that the analysis had the limitations of the study not being powered to show differences in men versus women, and the results are only applicable to the population studied who were at high risk of bleeding post PCI.

Commenting on the study at the ACC session, Jacqueline Tamis-Holland, MD, associate professor of medicine at the Icahn School of Medicine at Mount Sinai, described the presentation as “very interesting.”

“We know that women notoriously have higher bleeding risk than men, but this particular study did not show a difference in bleeding risk after adjusting for other confounding variables,” she said.

“In fact, one would think that the relative benefit of a treatment designed to decrease bleeding would be more favorable to women, but this analysis didn’t show that,” she added.

Dr. Vogel replied that the HR of the most serious type of bleeding (BARC 3 and 5) in women versus men was only reduced minimally after adjustment for baseline characteristics, “which still makes us think that there are additional factors that might be important and contribute to an increased risk for bleeding and especially more serous types of bleeding in women.”

She pointed out that, while there was a similar risk reduction in bleeding in women and men, there was a potential mortality benefit in women. “The question is whether this mortality benefit is due to reduced bleeding that might be greater in women than men, and the reality is we don’t have a lot of data on that.”

Dr. Vogel added: “We know about the relationship between bleeding and mortality very well but the impact of sex on this is really not well investigated. It would be worth investigating this further to come up with bleeding reduction strategies for women because this is a really important issue.”

This work was supported by an investigator-initiated grant from AstraZeneca. Dr. Mehran reported grants and personal fees (paid to the institution) from Abbott, Abiomed, Bayer, Beth Israel Deaconess, Bristol-Myers Squibb, Chiesi, Concept Medical Research, Medtronic, Novartis and DSI Research; grants from Applied Therapeutics, AstraZeneca, Cerecor, CSL Behring, OrbusNeich, and Zoll; personal fees from Boston Scientific, California Institute for Regenerative Medicine, Cine-Med Research, Janssen Scientific Affairs, ACC, and WebMD; personal fees paid to the institution from CardiaWave, Duke University, and Idorsia Pharmaceuticals; serving as a consultant or committee or advisory board member for Society for Cardiovascular Angiography and Interventions, the American Medical Association, and Regeneron Pharmaceuticals; and owning stock in ControlRad, Elixir Medical, and STEL outside the submitted work. Dr. Vogel disclosed no relevant financial relationships.

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

A new analysis from the TWILIGHT study has shown that, in the high-risk population undergoing percutaneous coronary intervention (PCI) enrolled in the study, the benefits of early aspirin withdrawal and continuation on ticagrelor monotherapy were similar in women and men.

But there were some interesting observations in the analysis suggesting possible additional benefits of this strategy for women.

“These data support the use of ticagrelor monotherapy in women and men, and importantly show that the absolute risk reduction of bleeding was higher in women, as their bleeding rates were higher,” senior author Roxana Mehran, MD, the Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, said in an interview.

“These data also support the need for prospective dual antiplatelet therapy deescalation studies in women,” Dr. Mehran added.

The main results of the TWILIGHT study showed that after a short period of dual antiplatelet therapy, a strategy of ticagrelor monotherapy, compared with continued dual therapy led to reduced bleeding without an increase in ischemic events among patients at high risk for bleeding or ischemic events after PCI.

The new gender-based analysis was presented by Birgit Vogel, MD, on May 15 at the annual scientific sessions of the American College of Cardiology. It was also published online in JAMA Cardiology to coincide with the ACC presentation.

Dr. Vogel, also from Wiener Cardiovascular Institute, explained that the current analysis was undertaken to investigate whether the TWILIGHT results varied in relation to sex, given that women are believed to have an increased risk for bleeding after PCI, compared with men.

“The current analysis showed that, while women did have a higher bleeding risk, compared to men, this was no longer significant after adjustment for baseline characteristics; and ischemic events were similar between the two sexes,” she reported.

“Results showed that withdrawing aspirin while continuing ticagrelor after 3 months of dual antiplatelet therapy was associated with a reduction in bleeding and preserved ischemic benefits in both women and men,” she added.

The TWILIGHT trial randomized 7,119 patients at high risk of ischemic or bleeding events who had undergone successful PCI with at least one drug-eluting stent and had completed 3 months of dual antiplatelet therapy to aspirin or placebo for an additional 12 months plus open-label ticagrelor.

The main results showed that the primary endpoint of Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding at 1 year was almost halved with ticagrelor monotherapy, occurring in 4% of these patients, compared with 7.1% of the ticagrelor/aspirin group (hazard ratio, 0.56). Ischemic events were similar in the two groups.

The current analysis focused on whether these effects varied in relation to sex.

Dr. Vogel noted that women made up 23.9% of the study population, were older than the men, and were more likely to have diabetes, chronic kidney disease, anemia and hypertension, while the men were more likely to be current smokers. Men had a higher incidence of coronary heart disease history, while women were more likely to have an ACS indication for PCI.

Unadjusted results showed a higher rate of BARC 2, 3, or 5 bleeding at 1 year in women (6.8%) versus men (5.2%), giving an HR of 1.32 (95% CI, 1.06-1.64).

But after adjustment for baseline characteristics, this became nonsignificant (HR, 1.20; 95% CI, 0.95-1.52).

Dr. Vogel pointed out that the most severe type of bleeding (BARC 3 and 5) was not attenuated as much by adjustment for baseline characteristics, with the HR reducing from 1.57 to 1.49.

The ischemic endpoint of death/stroke or MI was similar in men (4.0%) and women (3.5%), and this did not change after adjustment for baseline characteristics.

In terms of the two treatment groups, BARC 2, 3, or 5 bleeding was reduced to a similar extent with ticagrelor monotherapy in both men and women. This endpoint decreased from 8.6% in women on dual-antiplatelet therapy to 5.0% in women on ticagrelor alone (adjusted HR, 0.62) and from 6.6% to 3.7% in men (aHR, 0.57). But she noted that the absolute risk reduction in bleeding was greater in women (3.6%) versus men (2.9%).

“If we have a relative risk reduction in bleeding with early withdrawal of aspirin that is similar between the sexes but an overall higher risk of bleeding in women, that results in a greater absolute risk reduction,” Dr. Vogel commented.

The primary ischemic endpoint of death/MI/stroke was not increased in the ticagrelor group vs the dual antiplatelet group in either men (aHR, 1.06) or women (aHR, 1.04).
 

Greater reduction in mortality in women?

However, Dr. Vogel reported that there was a suggestion of a greater reduction in all-cause mortality with ticagrelor monotherapy in women versus men. “We found a significant interaction for treatment effect and sex for all-cause mortality, a prespecified endpoint, which was significantly lower in women treated with ticagrelor monotherapy, compared to dual antiplatelet therapy, but this was not the case in men.”

However, this observation was based on few events and should not be considered definitive, she added.

Dr. Vogel noted that the analysis had the limitations of the study not being powered to show differences in men versus women, and the results are only applicable to the population studied who were at high risk of bleeding post PCI.

Commenting on the study at the ACC session, Jacqueline Tamis-Holland, MD, associate professor of medicine at the Icahn School of Medicine at Mount Sinai, described the presentation as “very interesting.”

“We know that women notoriously have higher bleeding risk than men, but this particular study did not show a difference in bleeding risk after adjusting for other confounding variables,” she said.

“In fact, one would think that the relative benefit of a treatment designed to decrease bleeding would be more favorable to women, but this analysis didn’t show that,” she added.

Dr. Vogel replied that the HR of the most serious type of bleeding (BARC 3 and 5) in women versus men was only reduced minimally after adjustment for baseline characteristics, “which still makes us think that there are additional factors that might be important and contribute to an increased risk for bleeding and especially more serous types of bleeding in women.”

She pointed out that, while there was a similar risk reduction in bleeding in women and men, there was a potential mortality benefit in women. “The question is whether this mortality benefit is due to reduced bleeding that might be greater in women than men, and the reality is we don’t have a lot of data on that.”

Dr. Vogel added: “We know about the relationship between bleeding and mortality very well but the impact of sex on this is really not well investigated. It would be worth investigating this further to come up with bleeding reduction strategies for women because this is a really important issue.”

This work was supported by an investigator-initiated grant from AstraZeneca. Dr. Mehran reported grants and personal fees (paid to the institution) from Abbott, Abiomed, Bayer, Beth Israel Deaconess, Bristol-Myers Squibb, Chiesi, Concept Medical Research, Medtronic, Novartis and DSI Research; grants from Applied Therapeutics, AstraZeneca, Cerecor, CSL Behring, OrbusNeich, and Zoll; personal fees from Boston Scientific, California Institute for Regenerative Medicine, Cine-Med Research, Janssen Scientific Affairs, ACC, and WebMD; personal fees paid to the institution from CardiaWave, Duke University, and Idorsia Pharmaceuticals; serving as a consultant or committee or advisory board member for Society for Cardiovascular Angiography and Interventions, the American Medical Association, and Regeneron Pharmaceuticals; and owning stock in ControlRad, Elixir Medical, and STEL outside the submitted work. Dr. Vogel disclosed no relevant financial relationships.

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

In the wake of the COVID-19 pandemic, a population of patients has arisen with a range of symptoms and complications after surviving the acute phase of illness, according to Mezgebe Berhe, MD, of Baylor University Medical Center, Dallas.

Different terms have been used to describe this condition, including post COVID, long COVID, chronic COVID, and long-haulers, Dr. Berhe said in a presentation at SHM Converge, the annual conference of the Society of Hospital Medicine. However, the current medical consensus for a definition is post–acute COVID-19 syndrome.

Acute COVID-19 generally lasts for about 4 weeks after the onset of symptoms, and post–acute COVID-19 is generally defined as “persistent symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms,” he said. The postacute period may be broken into a subacute phase with symptoms and abnormalities present from 4-12 weeks beyond the acute phase, and then a chronic or post–acute COVID-19 syndrome, with symptoms and abnormalities present beyond 12 weeks after the onset of acute COVID-19.

Patients in the subacute or post–COVID-19 phase of illness are polymerase chain reaction negative and may have multiorgan symptomatology, said Dr. Berhe. Physical symptoms include fatigue, decline in quality of life, joint pain, and muscle weakness; reported mental symptoms include anxiety and depression; sleep disturbance; PTSD; cognitive disturbance (described by patients as “brain fog”); and headaches.

Pulmonary symptoms in post–acute COVID-19 patients include dyspnea, cough, and persistent oxygen requirements; patients also have reported palpitations and chest pain. Thromboembolism, chronic kidney disease, and hair loss also have been reported in COVID-19 patients in the postacute period.
 

What studies show

Early reports on postacute consequences of COVID-19 have been reported in published studies from the United States, Europe, and China, and the current treatment recommendations are based on findings from these studies, Dr. Berhe said.

In an observational cohort study from 38 hospitals in Michigan, researchers assessed 60-day outcomes for 1,250 COVID-19 patients who were discharged alive from the hospital. The researchers used medical record abstraction and telephone surveys to assess long-term symptoms. Overall, 6.7% of the patients died and 15.1% required hospital readmission. A total of 488 patients completed the telephone survey. Of these, 32.6% reported persistent symptoms, 18.9% reported new or worsening symptoms, 22.9% reported dyspnea while walking up stairs, 15.4% reported a cough, and 13.1% reported a persistent loss of taste or smell.

Data from multiple countries in Europe have shown similar prevalence of post–acute COVID-19 syndrome, but Dr. Berhe highlighted an Italian study in which 87% of 143 patients discharged from hospitals after acute COVID-19 reported at least one symptom at 60 day. “A decline in quality of life, as measured by the EuroQol visual analog scale, was reported by 44.1% of patients” in the Italian study, Dr. Berhe noted.

In a prospective cohort study conducted in Wuhan, China, researchers conducted a comprehensive in-person evaluation of symptoms in 1,733 COVID-19 patients at 6 months from symptom onset, and found that 76% reported at least one symptom, said Dr. Berhe. “Similar to other studies, muscle weakness and fatigue were the most common symptoms, followed by sleep problems and anxiety/depression. 

Dr. Berhe also cited a literature review published in Clinical Infectious Diseases that addressed COVID-19 in children; in one study of postacute COVID-19, approximately 12% of children had 5 weeks’ prevalence of persistent symptoms, compared with 22% of adults. This finding should remind clinicians that “Children can have devastating persistent symptoms following acute COVID-19 disease,” Dr. Berhe said.

In the post–acute COVID clinic

“Multidisciplinary collaboration is essential to provide integrated outpatient care to survivors of acute COVID-19,” Dr. Berhe said. Such collaboration includes pulmonary and cardiovascular symptom assessment through virtual or in-person follow-up at 4-6 weeks and at 12 weeks after hospital discharge. For those with dyspnea and persistent oxygen requirements at 12 weeks, consider the 6-minute walk test, pulmonary function test, chest x-ray, pulmonary embolism work-up, echocardiogram, and high-resolution CT of the chest as indicated.

With regard to neuropsychiatry, patients should be screened for anxiety, depression, PTSD, sleep disturbance, and cognitive impairment, said Dr. Berhe.

For hematology, “consider extended thromboprophylaxis for high-risk survivors based on shared decision-making,” he said. The incidence of thrombotic events post COVID is less than 5% so you have to be very selective and they should be in the highest-risk category.

COVID-19 patients with acute kidney infections should have a follow-up with a nephrologist soon after hospital discharge, he added.

From a primary care standpoint, early rehabilitation and patient education are important for managing symptoms; also consider recommending patient enrollment in research studies, Dr. Berhe said.

Dr. Berhe has been involved in multiple clinical trials of treating acute COVID-19 patients, but had no financial conflicts to disclose.

In the wake of the COVID-19 pandemic, a population of patients has arisen with a range of symptoms and complications after surviving the acute phase of illness, according to Mezgebe Berhe, MD, of Baylor University Medical Center, Dallas.

Different terms have been used to describe this condition, including post COVID, long COVID, chronic COVID, and long-haulers, Dr. Berhe said in a presentation at SHM Converge, the annual conference of the Society of Hospital Medicine. However, the current medical consensus for a definition is post–acute COVID-19 syndrome.

Acute COVID-19 generally lasts for about 4 weeks after the onset of symptoms, and post–acute COVID-19 is generally defined as “persistent symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms,” he said. The postacute period may be broken into a subacute phase with symptoms and abnormalities present from 4-12 weeks beyond the acute phase, and then a chronic or post–acute COVID-19 syndrome, with symptoms and abnormalities present beyond 12 weeks after the onset of acute COVID-19.

Patients in the subacute or post–COVID-19 phase of illness are polymerase chain reaction negative and may have multiorgan symptomatology, said Dr. Berhe. Physical symptoms include fatigue, decline in quality of life, joint pain, and muscle weakness; reported mental symptoms include anxiety and depression; sleep disturbance; PTSD; cognitive disturbance (described by patients as “brain fog”); and headaches.

Pulmonary symptoms in post–acute COVID-19 patients include dyspnea, cough, and persistent oxygen requirements; patients also have reported palpitations and chest pain. Thromboembolism, chronic kidney disease, and hair loss also have been reported in COVID-19 patients in the postacute period.
 

What studies show

Early reports on postacute consequences of COVID-19 have been reported in published studies from the United States, Europe, and China, and the current treatment recommendations are based on findings from these studies, Dr. Berhe said.

In an observational cohort study from 38 hospitals in Michigan, researchers assessed 60-day outcomes for 1,250 COVID-19 patients who were discharged alive from the hospital. The researchers used medical record abstraction and telephone surveys to assess long-term symptoms. Overall, 6.7% of the patients died and 15.1% required hospital readmission. A total of 488 patients completed the telephone survey. Of these, 32.6% reported persistent symptoms, 18.9% reported new or worsening symptoms, 22.9% reported dyspnea while walking up stairs, 15.4% reported a cough, and 13.1% reported a persistent loss of taste or smell.

Data from multiple countries in Europe have shown similar prevalence of post–acute COVID-19 syndrome, but Dr. Berhe highlighted an Italian study in which 87% of 143 patients discharged from hospitals after acute COVID-19 reported at least one symptom at 60 day. “A decline in quality of life, as measured by the EuroQol visual analog scale, was reported by 44.1% of patients” in the Italian study, Dr. Berhe noted.

In a prospective cohort study conducted in Wuhan, China, researchers conducted a comprehensive in-person evaluation of symptoms in 1,733 COVID-19 patients at 6 months from symptom onset, and found that 76% reported at least one symptom, said Dr. Berhe. “Similar to other studies, muscle weakness and fatigue were the most common symptoms, followed by sleep problems and anxiety/depression. 

Dr. Berhe also cited a literature review published in Clinical Infectious Diseases that addressed COVID-19 in children; in one study of postacute COVID-19, approximately 12% of children had 5 weeks’ prevalence of persistent symptoms, compared with 22% of adults. This finding should remind clinicians that “Children can have devastating persistent symptoms following acute COVID-19 disease,” Dr. Berhe said.

In the post–acute COVID clinic

“Multidisciplinary collaboration is essential to provide integrated outpatient care to survivors of acute COVID-19,” Dr. Berhe said. Such collaboration includes pulmonary and cardiovascular symptom assessment through virtual or in-person follow-up at 4-6 weeks and at 12 weeks after hospital discharge. For those with dyspnea and persistent oxygen requirements at 12 weeks, consider the 6-minute walk test, pulmonary function test, chest x-ray, pulmonary embolism work-up, echocardiogram, and high-resolution CT of the chest as indicated.

With regard to neuropsychiatry, patients should be screened for anxiety, depression, PTSD, sleep disturbance, and cognitive impairment, said Dr. Berhe.

For hematology, “consider extended thromboprophylaxis for high-risk survivors based on shared decision-making,” he said. The incidence of thrombotic events post COVID is less than 5% so you have to be very selective and they should be in the highest-risk category.

COVID-19 patients with acute kidney infections should have a follow-up with a nephrologist soon after hospital discharge, he added.

From a primary care standpoint, early rehabilitation and patient education are important for managing symptoms; also consider recommending patient enrollment in research studies, Dr. Berhe said.

Dr. Berhe has been involved in multiple clinical trials of treating acute COVID-19 patients, but had no financial conflicts to disclose.

In the wake of the COVID-19 pandemic, a population of patients has arisen with a range of symptoms and complications after surviving the acute phase of illness, according to Mezgebe Berhe, MD, of Baylor University Medical Center, Dallas.

Different terms have been used to describe this condition, including post COVID, long COVID, chronic COVID, and long-haulers, Dr. Berhe said in a presentation at SHM Converge, the annual conference of the Society of Hospital Medicine. However, the current medical consensus for a definition is post–acute COVID-19 syndrome.

Acute COVID-19 generally lasts for about 4 weeks after the onset of symptoms, and post–acute COVID-19 is generally defined as “persistent symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms,” he said. The postacute period may be broken into a subacute phase with symptoms and abnormalities present from 4-12 weeks beyond the acute phase, and then a chronic or post–acute COVID-19 syndrome, with symptoms and abnormalities present beyond 12 weeks after the onset of acute COVID-19.

Patients in the subacute or post–COVID-19 phase of illness are polymerase chain reaction negative and may have multiorgan symptomatology, said Dr. Berhe. Physical symptoms include fatigue, decline in quality of life, joint pain, and muscle weakness; reported mental symptoms include anxiety and depression; sleep disturbance; PTSD; cognitive disturbance (described by patients as “brain fog”); and headaches.

Pulmonary symptoms in post–acute COVID-19 patients include dyspnea, cough, and persistent oxygen requirements; patients also have reported palpitations and chest pain. Thromboembolism, chronic kidney disease, and hair loss also have been reported in COVID-19 patients in the postacute period.
 

What studies show

Early reports on postacute consequences of COVID-19 have been reported in published studies from the United States, Europe, and China, and the current treatment recommendations are based on findings from these studies, Dr. Berhe said.

In an observational cohort study from 38 hospitals in Michigan, researchers assessed 60-day outcomes for 1,250 COVID-19 patients who were discharged alive from the hospital. The researchers used medical record abstraction and telephone surveys to assess long-term symptoms. Overall, 6.7% of the patients died and 15.1% required hospital readmission. A total of 488 patients completed the telephone survey. Of these, 32.6% reported persistent symptoms, 18.9% reported new or worsening symptoms, 22.9% reported dyspnea while walking up stairs, 15.4% reported a cough, and 13.1% reported a persistent loss of taste or smell.

Data from multiple countries in Europe have shown similar prevalence of post–acute COVID-19 syndrome, but Dr. Berhe highlighted an Italian study in which 87% of 143 patients discharged from hospitals after acute COVID-19 reported at least one symptom at 60 day. “A decline in quality of life, as measured by the EuroQol visual analog scale, was reported by 44.1% of patients” in the Italian study, Dr. Berhe noted.

In a prospective cohort study conducted in Wuhan, China, researchers conducted a comprehensive in-person evaluation of symptoms in 1,733 COVID-19 patients at 6 months from symptom onset, and found that 76% reported at least one symptom, said Dr. Berhe. “Similar to other studies, muscle weakness and fatigue were the most common symptoms, followed by sleep problems and anxiety/depression. 

Dr. Berhe also cited a literature review published in Clinical Infectious Diseases that addressed COVID-19 in children; in one study of postacute COVID-19, approximately 12% of children had 5 weeks’ prevalence of persistent symptoms, compared with 22% of adults. This finding should remind clinicians that “Children can have devastating persistent symptoms following acute COVID-19 disease,” Dr. Berhe said.

In the post–acute COVID clinic

“Multidisciplinary collaboration is essential to provide integrated outpatient care to survivors of acute COVID-19,” Dr. Berhe said. Such collaboration includes pulmonary and cardiovascular symptom assessment through virtual or in-person follow-up at 4-6 weeks and at 12 weeks after hospital discharge. For those with dyspnea and persistent oxygen requirements at 12 weeks, consider the 6-minute walk test, pulmonary function test, chest x-ray, pulmonary embolism work-up, echocardiogram, and high-resolution CT of the chest as indicated.

With regard to neuropsychiatry, patients should be screened for anxiety, depression, PTSD, sleep disturbance, and cognitive impairment, said Dr. Berhe.

For hematology, “consider extended thromboprophylaxis for high-risk survivors based on shared decision-making,” he said. The incidence of thrombotic events post COVID is less than 5% so you have to be very selective and they should be in the highest-risk category.

COVID-19 patients with acute kidney infections should have a follow-up with a nephrologist soon after hospital discharge, he added.

From a primary care standpoint, early rehabilitation and patient education are important for managing symptoms; also consider recommending patient enrollment in research studies, Dr. Berhe said.

Dr. Berhe has been involved in multiple clinical trials of treating acute COVID-19 patients, but had no financial conflicts to disclose.

A parenting assessment can add value to a clinic visit by facilitating conversations about discipline and potentially mitigating adverse childhood experiences, based on survey data from 167 health care providers.

“Some of the most modifiable adverse childhood experiences (ACEs) are unhealthy parenting behaviors,” according to Amber J. Cooke, MD, of Vanderbilt University, Nashville, Tenn., and colleagues. “Despite the widespread use of standardized health assessment tools in pediatrics, a gap in services is that parenting assessments are not routinely administered,” they said.

In a study presented at the virtual meeting of the Pediatric Academic Societies, the researchers assessed clinicians’ perspectives on the use of the Quick Parenting Assessment (QPA), a validated 13-item parent support tool designed to identify children exposed to unhealthy parenting practices such as yelling, threatening, humiliating language, and physical punishment.

The researchers surveyed clinicians about how they integrated the QPA into a 15-month or 30-month well-child visit. Clinicians were trained to review the QPA and respond to parents during the visit.

Overall, the health care providers reported that the QPA could be reviewed with parents in less than 3 minutes for more than 80% of encounters.

The QPA takes approximately 1 minute for parents or caregivers to complete. Participating clinicians underwent training to learn how to interpret and respond to the QPA, and responded to a survey based on their inclusion of it in clinical visits. Key factors measured in the survey included the time needed for the clinician to review the QPA with the parent; whether the QPA increased clinicians’ objectivity about the level of support needed for the caregivers, whether the QPA affected communications with the caregiver about parenting, and whether the QPA added value to the well-child visit.

The survey respondents included resident physicians, nurse practitioners, and attending physicians. Approximately 75% of the providers said they were able to review the QPA in 1 minute or less; approximately 24% took 1-5 minutes, and less than 1% took longer than 5 minutes.

A majority of respondents (79%) said that the parent or caregiver was receptive to the QPA, and 74% said that the QPA facilitated communications with caregivers about parenting. In addition, 61% and 60% said the QPA improved the quality and value, respectively, of the visit, and 64% of the respondents said that the QPA increased their objectivity in assessing the level of support needed by caregivers.

Responses were similar, but slightly higher, in each category when the researchers compared providers who reviewed three or more QPAs with parents to those who reviewed less than three QPAs with parents.

The study findings were limited by several factors including the use of data from a single clinic site serving primarily low-income families, which might affect the generalizability of the results, the researchers noted. A lack of data on all QPA encounters might result in a participation bias as well, they said.

However, the results support the feasibility of the QPA, and clinical implications include mitigating ACEs, preventing child abuse, and enhancing the value of the well-child visit, they said. Next steps for research include integrating the QPA into 5-year and 8-year well-child visits, they concluded.
 

Data support value of parenting assessment screening tool

“In order to be useful, a screening tool has to be validated, not add significant time to the well-child visit, and result in useful data for the clinician to more effectively serve their families,” Suzanne C. Boulter, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H., said in an interview. “The Quick Parenting Assessment Screen was developed at Vanderbilt, is free for clinicians to use, and takes an average of 1 minute to assess,” she noted. “This poster highlights a study that was done by residents and attendings at Vanderbilt who administered the tool to caregivers attending their well child clinics.”

Dr. Boulter explained the study was important because “there is increased emphasis on the social determinants of health within the context of well child care, and discipline is one aspect of significance in the assessment of adverse childhood experiences,” she said. “The practitioners overall felt that the tool improved communication with their caregivers, which increased the quality of the visit. It was also surprising that 79% of the providers noted that the caregiver was receptive to the assessment tool,” Dr. Boulter added. 

“In general, this tool offers clinicians a quick overview of disciplinary practices in the households of their patients. It would be useful, as a next step, to expand the testing to a wider socioeconomic population of families,” she concluded.

The researchers had no financial conflicts to disclose. Dr. Boulter had no financial conflicts to disclose, but serves on the Pediatric News Editorial Advisory Board.

A parenting assessment can add value to a clinic visit by facilitating conversations about discipline and potentially mitigating adverse childhood experiences, based on survey data from 167 health care providers.

“Some of the most modifiable adverse childhood experiences (ACEs) are unhealthy parenting behaviors,” according to Amber J. Cooke, MD, of Vanderbilt University, Nashville, Tenn., and colleagues. “Despite the widespread use of standardized health assessment tools in pediatrics, a gap in services is that parenting assessments are not routinely administered,” they said.

In a study presented at the virtual meeting of the Pediatric Academic Societies, the researchers assessed clinicians’ perspectives on the use of the Quick Parenting Assessment (QPA), a validated 13-item parent support tool designed to identify children exposed to unhealthy parenting practices such as yelling, threatening, humiliating language, and physical punishment.

The researchers surveyed clinicians about how they integrated the QPA into a 15-month or 30-month well-child visit. Clinicians were trained to review the QPA and respond to parents during the visit.

Overall, the health care providers reported that the QPA could be reviewed with parents in less than 3 minutes for more than 80% of encounters.

The QPA takes approximately 1 minute for parents or caregivers to complete. Participating clinicians underwent training to learn how to interpret and respond to the QPA, and responded to a survey based on their inclusion of it in clinical visits. Key factors measured in the survey included the time needed for the clinician to review the QPA with the parent; whether the QPA increased clinicians’ objectivity about the level of support needed for the caregivers, whether the QPA affected communications with the caregiver about parenting, and whether the QPA added value to the well-child visit.

The survey respondents included resident physicians, nurse practitioners, and attending physicians. Approximately 75% of the providers said they were able to review the QPA in 1 minute or less; approximately 24% took 1-5 minutes, and less than 1% took longer than 5 minutes.

A majority of respondents (79%) said that the parent or caregiver was receptive to the QPA, and 74% said that the QPA facilitated communications with caregivers about parenting. In addition, 61% and 60% said the QPA improved the quality and value, respectively, of the visit, and 64% of the respondents said that the QPA increased their objectivity in assessing the level of support needed by caregivers.

Responses were similar, but slightly higher, in each category when the researchers compared providers who reviewed three or more QPAs with parents to those who reviewed less than three QPAs with parents.

The study findings were limited by several factors including the use of data from a single clinic site serving primarily low-income families, which might affect the generalizability of the results, the researchers noted. A lack of data on all QPA encounters might result in a participation bias as well, they said.

However, the results support the feasibility of the QPA, and clinical implications include mitigating ACEs, preventing child abuse, and enhancing the value of the well-child visit, they said. Next steps for research include integrating the QPA into 5-year and 8-year well-child visits, they concluded.
 

Data support value of parenting assessment screening tool

“In order to be useful, a screening tool has to be validated, not add significant time to the well-child visit, and result in useful data for the clinician to more effectively serve their families,” Suzanne C. Boulter, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H., said in an interview. “The Quick Parenting Assessment Screen was developed at Vanderbilt, is free for clinicians to use, and takes an average of 1 minute to assess,” she noted. “This poster highlights a study that was done by residents and attendings at Vanderbilt who administered the tool to caregivers attending their well child clinics.”

Dr. Boulter explained the study was important because “there is increased emphasis on the social determinants of health within the context of well child care, and discipline is one aspect of significance in the assessment of adverse childhood experiences,” she said. “The practitioners overall felt that the tool improved communication with their caregivers, which increased the quality of the visit. It was also surprising that 79% of the providers noted that the caregiver was receptive to the assessment tool,” Dr. Boulter added. 

“In general, this tool offers clinicians a quick overview of disciplinary practices in the households of their patients. It would be useful, as a next step, to expand the testing to a wider socioeconomic population of families,” she concluded.

The researchers had no financial conflicts to disclose. Dr. Boulter had no financial conflicts to disclose, but serves on the Pediatric News Editorial Advisory Board.

A parenting assessment can add value to a clinic visit by facilitating conversations about discipline and potentially mitigating adverse childhood experiences, based on survey data from 167 health care providers.

“Some of the most modifiable adverse childhood experiences (ACEs) are unhealthy parenting behaviors,” according to Amber J. Cooke, MD, of Vanderbilt University, Nashville, Tenn., and colleagues. “Despite the widespread use of standardized health assessment tools in pediatrics, a gap in services is that parenting assessments are not routinely administered,” they said.

In a study presented at the virtual meeting of the Pediatric Academic Societies, the researchers assessed clinicians’ perspectives on the use of the Quick Parenting Assessment (QPA), a validated 13-item parent support tool designed to identify children exposed to unhealthy parenting practices such as yelling, threatening, humiliating language, and physical punishment.

The researchers surveyed clinicians about how they integrated the QPA into a 15-month or 30-month well-child visit. Clinicians were trained to review the QPA and respond to parents during the visit.

Overall, the health care providers reported that the QPA could be reviewed with parents in less than 3 minutes for more than 80% of encounters.

The QPA takes approximately 1 minute for parents or caregivers to complete. Participating clinicians underwent training to learn how to interpret and respond to the QPA, and responded to a survey based on their inclusion of it in clinical visits. Key factors measured in the survey included the time needed for the clinician to review the QPA with the parent; whether the QPA increased clinicians’ objectivity about the level of support needed for the caregivers, whether the QPA affected communications with the caregiver about parenting, and whether the QPA added value to the well-child visit.

The survey respondents included resident physicians, nurse practitioners, and attending physicians. Approximately 75% of the providers said they were able to review the QPA in 1 minute or less; approximately 24% took 1-5 minutes, and less than 1% took longer than 5 minutes.

A majority of respondents (79%) said that the parent or caregiver was receptive to the QPA, and 74% said that the QPA facilitated communications with caregivers about parenting. In addition, 61% and 60% said the QPA improved the quality and value, respectively, of the visit, and 64% of the respondents said that the QPA increased their objectivity in assessing the level of support needed by caregivers.

Responses were similar, but slightly higher, in each category when the researchers compared providers who reviewed three or more QPAs with parents to those who reviewed less than three QPAs with parents.

The study findings were limited by several factors including the use of data from a single clinic site serving primarily low-income families, which might affect the generalizability of the results, the researchers noted. A lack of data on all QPA encounters might result in a participation bias as well, they said.

However, the results support the feasibility of the QPA, and clinical implications include mitigating ACEs, preventing child abuse, and enhancing the value of the well-child visit, they said. Next steps for research include integrating the QPA into 5-year and 8-year well-child visits, they concluded.
 

Data support value of parenting assessment screening tool

“In order to be useful, a screening tool has to be validated, not add significant time to the well-child visit, and result in useful data for the clinician to more effectively serve their families,” Suzanne C. Boulter, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H., said in an interview. “The Quick Parenting Assessment Screen was developed at Vanderbilt, is free for clinicians to use, and takes an average of 1 minute to assess,” she noted. “This poster highlights a study that was done by residents and attendings at Vanderbilt who administered the tool to caregivers attending their well child clinics.”

Dr. Boulter explained the study was important because “there is increased emphasis on the social determinants of health within the context of well child care, and discipline is one aspect of significance in the assessment of adverse childhood experiences,” she said. “The practitioners overall felt that the tool improved communication with their caregivers, which increased the quality of the visit. It was also surprising that 79% of the providers noted that the caregiver was receptive to the assessment tool,” Dr. Boulter added. 

“In general, this tool offers clinicians a quick overview of disciplinary practices in the households of their patients. It would be useful, as a next step, to expand the testing to a wider socioeconomic population of families,” she concluded.

The researchers had no financial conflicts to disclose. Dr. Boulter had no financial conflicts to disclose, but serves on the Pediatric News Editorial Advisory Board.

Combined reflectance confocal microscopy–optical coherence tomography is a noninvasive tool that could prove useful in the detection of squamous cell carcinoma (SCC) and distinguishing SCC in-situ and actinic keratosis (AK) from invasive SCC, results from a small prospective study demonstrated.

“A solitary scaly papule or plaque could represent an inflammatory or neoplastic process, and when neoplastic, it could be benign, premalignant, malignant in situ, or invasive malignant,” lead study author Abdullah Aleisa, MD, said in an interview during the annual conference of the American Society for Laser Medicine and Surgery. Noninvasive imaging devices, such as reflectance confocal microscopy (RCM) and optical coherence tomography (OCT), “have been used to help in the diagnosis of those clinically suspicious lesions, however each device has its own limitation.”

RCM images are horizontal sections of the skin with high cellular resolution but limited to 250 mcm of depth in skin, he said, while OCT images are vertical sections of the skin with low cellular resolution, but image up to 1,000-2,000 mcm of depth in skin.

“Combined RCM-OCT enables high cellular resolution and deep tissue evaluation,” said Dr. Aleisa, a micrographic surgery and dermatologic oncology fellow at Memorial Sloan Kettering Cancer Center, New York. “The value of combined RCM-OCT has been shown in the detection and depth assessment of basal cell carcinoma, but it has never been studied in SCC. Our objective is to combine RCM and OCT simultaneously to detect SCC and assess the depth of invasion.”

Between September and December 2020, Dr. Aleisa and colleagues prospectively imaged 36 lesions suspicious of SCC, SCC in situ, or AK between September 2020 and December 2020. The mean age of the cohort was 68 years and 63% were male. Using a prototype device from Andover, Mass.–based Caliber I.D., the investigators performed handheld RCM-OCT imaging at the center of clinically suspected lesions before biopsy and to previously diagnosed lesions before Mohs micrographic surgery (to check for residual tumor) and correlated RCM-OCT findings with histopathology results. A total of 36 lesions were treated.

Dr. Aleisa reported that most common RCM-OCT feature for invasive SCC was presence of vertical blood vessels (in 89% of lesions), while for SCC in situ/AK, it was acanthosis and parakeratosis without vertical blood vessels (in 84% of lesions). For the detection of invasive SCC, RCM-OCT had a sensitivity of 82%, a specificity of 92%, a negative predictive value of 92%, and a positive predictive value of 82%. For the detection of SCC in situ/AK, RCM-OCT had a sensitivity of 86%, a specificity of 100%, a negative predictive value of 92%, and a positive predictive value of 100%. The OCT depth measurement correlated well with histopathology with a concordance correlation coefficient of r2 = 0.9.

“Using RCM’s high-resolution pictures allowed us to easily spot the vertical ‘buttonhole’ vessels associated with SCC,” Dr. Aleisa said. “However, given the depth limitation of RCM, the distinction between SCC in situ and invasive SCC could not be accomplished using RCM alone. Therefore, having simultaneous OCT live feedback to the RCM images in the combined RCM-OCT device enabled us to assess the depth of those vertical ‘buttonholes’ and distinguish between SCC in situ and invasive SCC.”

He acknowledged certain limitations of the approach, including that it requires approximately 20 minutes per imaging session, there is a steep learning curve for interpreting images, and certain anatomical sites are challenging to image, especially the nose, periocular area, and lip.

The study won a “best of session” emerging technologies abstract award from the ASLMS.

Milind Rajadhyaksha, PhD, of Memorial Sloan Kettering Cancer Center helped to develop the prototype device. Dr. Aleisa reported having no relevant financial disclosures.

dbrunk@mdedge.com

Combined reflectance confocal microscopy–optical coherence tomography is a noninvasive tool that could prove useful in the detection of squamous cell carcinoma (SCC) and distinguishing SCC in-situ and actinic keratosis (AK) from invasive SCC, results from a small prospective study demonstrated.

“A solitary scaly papule or plaque could represent an inflammatory or neoplastic process, and when neoplastic, it could be benign, premalignant, malignant in situ, or invasive malignant,” lead study author Abdullah Aleisa, MD, said in an interview during the annual conference of the American Society for Laser Medicine and Surgery. Noninvasive imaging devices, such as reflectance confocal microscopy (RCM) and optical coherence tomography (OCT), “have been used to help in the diagnosis of those clinically suspicious lesions, however each device has its own limitation.”

RCM images are horizontal sections of the skin with high cellular resolution but limited to 250 mcm of depth in skin, he said, while OCT images are vertical sections of the skin with low cellular resolution, but image up to 1,000-2,000 mcm of depth in skin.

“Combined RCM-OCT enables high cellular resolution and deep tissue evaluation,” said Dr. Aleisa, a micrographic surgery and dermatologic oncology fellow at Memorial Sloan Kettering Cancer Center, New York. “The value of combined RCM-OCT has been shown in the detection and depth assessment of basal cell carcinoma, but it has never been studied in SCC. Our objective is to combine RCM and OCT simultaneously to detect SCC and assess the depth of invasion.”

Between September and December 2020, Dr. Aleisa and colleagues prospectively imaged 36 lesions suspicious of SCC, SCC in situ, or AK between September 2020 and December 2020. The mean age of the cohort was 68 years and 63% were male. Using a prototype device from Andover, Mass.–based Caliber I.D., the investigators performed handheld RCM-OCT imaging at the center of clinically suspected lesions before biopsy and to previously diagnosed lesions before Mohs micrographic surgery (to check for residual tumor) and correlated RCM-OCT findings with histopathology results. A total of 36 lesions were treated.

Dr. Aleisa reported that most common RCM-OCT feature for invasive SCC was presence of vertical blood vessels (in 89% of lesions), while for SCC in situ/AK, it was acanthosis and parakeratosis without vertical blood vessels (in 84% of lesions). For the detection of invasive SCC, RCM-OCT had a sensitivity of 82%, a specificity of 92%, a negative predictive value of 92%, and a positive predictive value of 82%. For the detection of SCC in situ/AK, RCM-OCT had a sensitivity of 86%, a specificity of 100%, a negative predictive value of 92%, and a positive predictive value of 100%. The OCT depth measurement correlated well with histopathology with a concordance correlation coefficient of r2 = 0.9.

“Using RCM’s high-resolution pictures allowed us to easily spot the vertical ‘buttonhole’ vessels associated with SCC,” Dr. Aleisa said. “However, given the depth limitation of RCM, the distinction between SCC in situ and invasive SCC could not be accomplished using RCM alone. Therefore, having simultaneous OCT live feedback to the RCM images in the combined RCM-OCT device enabled us to assess the depth of those vertical ‘buttonholes’ and distinguish between SCC in situ and invasive SCC.”

He acknowledged certain limitations of the approach, including that it requires approximately 20 minutes per imaging session, there is a steep learning curve for interpreting images, and certain anatomical sites are challenging to image, especially the nose, periocular area, and lip.

The study won a “best of session” emerging technologies abstract award from the ASLMS.

Milind Rajadhyaksha, PhD, of Memorial Sloan Kettering Cancer Center helped to develop the prototype device. Dr. Aleisa reported having no relevant financial disclosures.

dbrunk@mdedge.com

Combined reflectance confocal microscopy–optical coherence tomography is a noninvasive tool that could prove useful in the detection of squamous cell carcinoma (SCC) and distinguishing SCC in-situ and actinic keratosis (AK) from invasive SCC, results from a small prospective study demonstrated.

“A solitary scaly papule or plaque could represent an inflammatory or neoplastic process, and when neoplastic, it could be benign, premalignant, malignant in situ, or invasive malignant,” lead study author Abdullah Aleisa, MD, said in an interview during the annual conference of the American Society for Laser Medicine and Surgery. Noninvasive imaging devices, such as reflectance confocal microscopy (RCM) and optical coherence tomography (OCT), “have been used to help in the diagnosis of those clinically suspicious lesions, however each device has its own limitation.”

RCM images are horizontal sections of the skin with high cellular resolution but limited to 250 mcm of depth in skin, he said, while OCT images are vertical sections of the skin with low cellular resolution, but image up to 1,000-2,000 mcm of depth in skin.

“Combined RCM-OCT enables high cellular resolution and deep tissue evaluation,” said Dr. Aleisa, a micrographic surgery and dermatologic oncology fellow at Memorial Sloan Kettering Cancer Center, New York. “The value of combined RCM-OCT has been shown in the detection and depth assessment of basal cell carcinoma, but it has never been studied in SCC. Our objective is to combine RCM and OCT simultaneously to detect SCC and assess the depth of invasion.”

Between September and December 2020, Dr. Aleisa and colleagues prospectively imaged 36 lesions suspicious of SCC, SCC in situ, or AK between September 2020 and December 2020. The mean age of the cohort was 68 years and 63% were male. Using a prototype device from Andover, Mass.–based Caliber I.D., the investigators performed handheld RCM-OCT imaging at the center of clinically suspected lesions before biopsy and to previously diagnosed lesions before Mohs micrographic surgery (to check for residual tumor) and correlated RCM-OCT findings with histopathology results. A total of 36 lesions were treated.

Dr. Aleisa reported that most common RCM-OCT feature for invasive SCC was presence of vertical blood vessels (in 89% of lesions), while for SCC in situ/AK, it was acanthosis and parakeratosis without vertical blood vessels (in 84% of lesions). For the detection of invasive SCC, RCM-OCT had a sensitivity of 82%, a specificity of 92%, a negative predictive value of 92%, and a positive predictive value of 82%. For the detection of SCC in situ/AK, RCM-OCT had a sensitivity of 86%, a specificity of 100%, a negative predictive value of 92%, and a positive predictive value of 100%. The OCT depth measurement correlated well with histopathology with a concordance correlation coefficient of r2 = 0.9.

“Using RCM’s high-resolution pictures allowed us to easily spot the vertical ‘buttonhole’ vessels associated with SCC,” Dr. Aleisa said. “However, given the depth limitation of RCM, the distinction between SCC in situ and invasive SCC could not be accomplished using RCM alone. Therefore, having simultaneous OCT live feedback to the RCM images in the combined RCM-OCT device enabled us to assess the depth of those vertical ‘buttonholes’ and distinguish between SCC in situ and invasive SCC.”

He acknowledged certain limitations of the approach, including that it requires approximately 20 minutes per imaging session, there is a steep learning curve for interpreting images, and certain anatomical sites are challenging to image, especially the nose, periocular area, and lip.

The study won a “best of session” emerging technologies abstract award from the ASLMS.

Milind Rajadhyaksha, PhD, of Memorial Sloan Kettering Cancer Center helped to develop the prototype device. Dr. Aleisa reported having no relevant financial disclosures.

dbrunk@mdedge.com

A cohort analysis using advanced strategies to minimize the impact of confounders has concluded that the current Food and Drug Administration warning about paclitaxel-coated devices used for femoropopliteal endovascular treatment should be lifted, according to investigators of a study called SAFE-PAD.

In early 2019, an FDA letter to clinicians warned that endovascular stents and balloons coated with paclitaxel might increase mortality, recounted the principal investigator of SAFE-PAD, Eric A. Secemsky, MD, director of vascular intervention, Beth Israel Deaconess Hospital, Boston.

An FDA advisory committee that was subsequently convened in 2019 did not elect to remove these devices from the market, but it did call for restrictions and for the collection of more safety data. In the absence of a clear mechanism of risk, and in the context of perceived problems with data suggesting harm, Dr. Secemsky said that there was interest in a conclusive answer.

The problem was that a randomized controlled trial, even if funding were available, was considered impractical, he noted in presenting SAFE-PAD at the annual scientific sessions of the American College of Cardiology.

In the initial meta-analysis that suggested an increased mortality risk, no risk was seen in the first year after exposure, and it climbed to only 3.5% after 2 years. As a result, the definitive 2-year study with sufficient power to produce conclusive results was an estimated 40,000 patients. Even if extended to 5 years, 20,000 patients would be needed, according to Dr. Secemsky.
 

SAFE-PAD born of collaboration

An alternative solution was required, which is why “we became engaged with the FDA to design a real-world study for use in making a regulatory decision,” Dr. Secemsky said.

SAFE-PAD, designed with feedback from the FDA, employed sophisticated methodologies to account for known and unknown confounding in the Medicare cohort data used for this study.

Of 168,553 Medicare fee-for-service patients undergoing femoropopliteal artery revascularization with a stent, a balloon, or both at 2,978 institutions, 70,584 (42%) were treated with a paclitaxel drug-coated device (DCD) and the remainder were managed with a non–drug-coated device (NDCD).

The groups were compared with a primary outcome of all-cause mortality in a design to evaluate DCD for noninferiority. Several secondary outcomes, such as repeated lower extremity revascularization, were also evaluated.

To create balanced groups, inverse probability of treatment weighting (IPTW) blinded to outcome was the primary analytic strategy. In addition, several sensitivity analyses were applied, including a technique that tests for the impact of a hypothetical variable that allows adjustment for an unknown confounder.

After a median follow-up of 2.7 years (longest more than 5 years), the cumulative mortality after weighting was 53.8% in the DCD group and 55.1% in the NDCD group. The 5% advantage for the DCD group (hazard ratio, 0.95; 95% confidence interval, 0.94-0.97) ensured noninferiority (P < .001).

On unweighted analysis, the mortality difference favoring DCD was even greater (HR, 0.85; 95% CI, 0.82–0.85).

None of the sensitivity analyses – including a multivariable Cox regression analysis, an instrumental variable analysis, and a falsification endpoints analysis that employed myocardial infarction, pneumonia, and heart failure – altered the conclusion. The hypothetical variable analysis produced the same result.

“A missing confounder would need to be more prevalent and more strongly associated to outcome than any measured variable in this analysis,” reported Dr. Secemsky, indicating that this ruled out essentially any probability of this occurring.

A subgroup analysis told the same story. By hazard ratio for the outcome of mortality, DCD was consistently favored over NDCD for groups characterized by low risk (HR, 0.98), stent implantation (HR, 0.97), receipt of balloon angioplasty alone (HR, 0.94), having critical limb ischemia (HR, 0.95) or no critical limb ischemia (HR, 0.97), and being managed inpatient (HR, 0.97) or outpatient (HR, 0.95).

The results of SAFE-PAD were simultaneously published with Dr. Secemsky’s ACC presentation.
 

Value of revascularization questioned

In an accompanying editorial, the coauthors Rita F. Redberg, MD, of the University of California, San Francisco, and Mary M. McDermott, MD, of Northwestern University, Chicago, reiterated the findings and the conclusions, but used the forum to draw attention to the low survival rates.

“Thus, while this well-done observational study provides new information,” they wrote, “a major conclusion should be that mortality is high among Medicare beneficiaries undergoing revascularization [for peripheral artery disease] with any devices.”
 

‘Very impressive’ methods

Marc P. Bonaca, MD, director of vascular research, University of Colorado at Denver, Aurora, called the methods to ensure the validity of the conclusions of this study “very impressive.” In situations where prospective randomized trials are impractical, he suggested that this type of approach might answer an unmet need.

“We have always desired the ability to look at these large datasets with a lot of power to answer important questions,” he said. While “the issue has always been residual confounding,” he expressed interest in further verifications that this type of methodology can serve as a template for data analysis to guide other regulatory decisions.

Dr. Secemsky reports financial relationships with Abbott, Bayer, Boston Scientific, Cook, CSI, Inari, Janssen, Medtronic, and Phillips. Dr. Redford reports no potential conflicts of interest. Dr. McDermott reports a financial relationship with Regeneron. Dr. Bonaca reports financial relationships with Amgen, AstraZeneca, Bayer, Janssen Merck, Novo Nordisk, Pfizer, and Sanofi.

A cohort analysis using advanced strategies to minimize the impact of confounders has concluded that the current Food and Drug Administration warning about paclitaxel-coated devices used for femoropopliteal endovascular treatment should be lifted, according to investigators of a study called SAFE-PAD.

In early 2019, an FDA letter to clinicians warned that endovascular stents and balloons coated with paclitaxel might increase mortality, recounted the principal investigator of SAFE-PAD, Eric A. Secemsky, MD, director of vascular intervention, Beth Israel Deaconess Hospital, Boston.

An FDA advisory committee that was subsequently convened in 2019 did not elect to remove these devices from the market, but it did call for restrictions and for the collection of more safety data. In the absence of a clear mechanism of risk, and in the context of perceived problems with data suggesting harm, Dr. Secemsky said that there was interest in a conclusive answer.

The problem was that a randomized controlled trial, even if funding were available, was considered impractical, he noted in presenting SAFE-PAD at the annual scientific sessions of the American College of Cardiology.

In the initial meta-analysis that suggested an increased mortality risk, no risk was seen in the first year after exposure, and it climbed to only 3.5% after 2 years. As a result, the definitive 2-year study with sufficient power to produce conclusive results was an estimated 40,000 patients. Even if extended to 5 years, 20,000 patients would be needed, according to Dr. Secemsky.
 

SAFE-PAD born of collaboration

An alternative solution was required, which is why “we became engaged with the FDA to design a real-world study for use in making a regulatory decision,” Dr. Secemsky said.

SAFE-PAD, designed with feedback from the FDA, employed sophisticated methodologies to account for known and unknown confounding in the Medicare cohort data used for this study.

Of 168,553 Medicare fee-for-service patients undergoing femoropopliteal artery revascularization with a stent, a balloon, or both at 2,978 institutions, 70,584 (42%) were treated with a paclitaxel drug-coated device (DCD) and the remainder were managed with a non–drug-coated device (NDCD).

The groups were compared with a primary outcome of all-cause mortality in a design to evaluate DCD for noninferiority. Several secondary outcomes, such as repeated lower extremity revascularization, were also evaluated.

To create balanced groups, inverse probability of treatment weighting (IPTW) blinded to outcome was the primary analytic strategy. In addition, several sensitivity analyses were applied, including a technique that tests for the impact of a hypothetical variable that allows adjustment for an unknown confounder.

After a median follow-up of 2.7 years (longest more than 5 years), the cumulative mortality after weighting was 53.8% in the DCD group and 55.1% in the NDCD group. The 5% advantage for the DCD group (hazard ratio, 0.95; 95% confidence interval, 0.94-0.97) ensured noninferiority (P < .001).

On unweighted analysis, the mortality difference favoring DCD was even greater (HR, 0.85; 95% CI, 0.82–0.85).

None of the sensitivity analyses – including a multivariable Cox regression analysis, an instrumental variable analysis, and a falsification endpoints analysis that employed myocardial infarction, pneumonia, and heart failure – altered the conclusion. The hypothetical variable analysis produced the same result.

“A missing confounder would need to be more prevalent and more strongly associated to outcome than any measured variable in this analysis,” reported Dr. Secemsky, indicating that this ruled out essentially any probability of this occurring.

A subgroup analysis told the same story. By hazard ratio for the outcome of mortality, DCD was consistently favored over NDCD for groups characterized by low risk (HR, 0.98), stent implantation (HR, 0.97), receipt of balloon angioplasty alone (HR, 0.94), having critical limb ischemia (HR, 0.95) or no critical limb ischemia (HR, 0.97), and being managed inpatient (HR, 0.97) or outpatient (HR, 0.95).

The results of SAFE-PAD were simultaneously published with Dr. Secemsky’s ACC presentation.
 

Value of revascularization questioned

In an accompanying editorial, the coauthors Rita F. Redberg, MD, of the University of California, San Francisco, and Mary M. McDermott, MD, of Northwestern University, Chicago, reiterated the findings and the conclusions, but used the forum to draw attention to the low survival rates.

“Thus, while this well-done observational study provides new information,” they wrote, “a major conclusion should be that mortality is high among Medicare beneficiaries undergoing revascularization [for peripheral artery disease] with any devices.”
 

‘Very impressive’ methods

Marc P. Bonaca, MD, director of vascular research, University of Colorado at Denver, Aurora, called the methods to ensure the validity of the conclusions of this study “very impressive.” In situations where prospective randomized trials are impractical, he suggested that this type of approach might answer an unmet need.

“We have always desired the ability to look at these large datasets with a lot of power to answer important questions,” he said. While “the issue has always been residual confounding,” he expressed interest in further verifications that this type of methodology can serve as a template for data analysis to guide other regulatory decisions.

Dr. Secemsky reports financial relationships with Abbott, Bayer, Boston Scientific, Cook, CSI, Inari, Janssen, Medtronic, and Phillips. Dr. Redford reports no potential conflicts of interest. Dr. McDermott reports a financial relationship with Regeneron. Dr. Bonaca reports financial relationships with Amgen, AstraZeneca, Bayer, Janssen Merck, Novo Nordisk, Pfizer, and Sanofi.

A cohort analysis using advanced strategies to minimize the impact of confounders has concluded that the current Food and Drug Administration warning about paclitaxel-coated devices used for femoropopliteal endovascular treatment should be lifted, according to investigators of a study called SAFE-PAD.

In early 2019, an FDA letter to clinicians warned that endovascular stents and balloons coated with paclitaxel might increase mortality, recounted the principal investigator of SAFE-PAD, Eric A. Secemsky, MD, director of vascular intervention, Beth Israel Deaconess Hospital, Boston.

An FDA advisory committee that was subsequently convened in 2019 did not elect to remove these devices from the market, but it did call for restrictions and for the collection of more safety data. In the absence of a clear mechanism of risk, and in the context of perceived problems with data suggesting harm, Dr. Secemsky said that there was interest in a conclusive answer.

The problem was that a randomized controlled trial, even if funding were available, was considered impractical, he noted in presenting SAFE-PAD at the annual scientific sessions of the American College of Cardiology.

In the initial meta-analysis that suggested an increased mortality risk, no risk was seen in the first year after exposure, and it climbed to only 3.5% after 2 years. As a result, the definitive 2-year study with sufficient power to produce conclusive results was an estimated 40,000 patients. Even if extended to 5 years, 20,000 patients would be needed, according to Dr. Secemsky.
 

SAFE-PAD born of collaboration

An alternative solution was required, which is why “we became engaged with the FDA to design a real-world study for use in making a regulatory decision,” Dr. Secemsky said.

SAFE-PAD, designed with feedback from the FDA, employed sophisticated methodologies to account for known and unknown confounding in the Medicare cohort data used for this study.

Of 168,553 Medicare fee-for-service patients undergoing femoropopliteal artery revascularization with a stent, a balloon, or both at 2,978 institutions, 70,584 (42%) were treated with a paclitaxel drug-coated device (DCD) and the remainder were managed with a non–drug-coated device (NDCD).

The groups were compared with a primary outcome of all-cause mortality in a design to evaluate DCD for noninferiority. Several secondary outcomes, such as repeated lower extremity revascularization, were also evaluated.

To create balanced groups, inverse probability of treatment weighting (IPTW) blinded to outcome was the primary analytic strategy. In addition, several sensitivity analyses were applied, including a technique that tests for the impact of a hypothetical variable that allows adjustment for an unknown confounder.

After a median follow-up of 2.7 years (longest more than 5 years), the cumulative mortality after weighting was 53.8% in the DCD group and 55.1% in the NDCD group. The 5% advantage for the DCD group (hazard ratio, 0.95; 95% confidence interval, 0.94-0.97) ensured noninferiority (P < .001).

On unweighted analysis, the mortality difference favoring DCD was even greater (HR, 0.85; 95% CI, 0.82–0.85).

None of the sensitivity analyses – including a multivariable Cox regression analysis, an instrumental variable analysis, and a falsification endpoints analysis that employed myocardial infarction, pneumonia, and heart failure – altered the conclusion. The hypothetical variable analysis produced the same result.

“A missing confounder would need to be more prevalent and more strongly associated to outcome than any measured variable in this analysis,” reported Dr. Secemsky, indicating that this ruled out essentially any probability of this occurring.

A subgroup analysis told the same story. By hazard ratio for the outcome of mortality, DCD was consistently favored over NDCD for groups characterized by low risk (HR, 0.98), stent implantation (HR, 0.97), receipt of balloon angioplasty alone (HR, 0.94), having critical limb ischemia (HR, 0.95) or no critical limb ischemia (HR, 0.97), and being managed inpatient (HR, 0.97) or outpatient (HR, 0.95).

The results of SAFE-PAD were simultaneously published with Dr. Secemsky’s ACC presentation.
 

Value of revascularization questioned

In an accompanying editorial, the coauthors Rita F. Redberg, MD, of the University of California, San Francisco, and Mary M. McDermott, MD, of Northwestern University, Chicago, reiterated the findings and the conclusions, but used the forum to draw attention to the low survival rates.

“Thus, while this well-done observational study provides new information,” they wrote, “a major conclusion should be that mortality is high among Medicare beneficiaries undergoing revascularization [for peripheral artery disease] with any devices.”
 

‘Very impressive’ methods

Marc P. Bonaca, MD, director of vascular research, University of Colorado at Denver, Aurora, called the methods to ensure the validity of the conclusions of this study “very impressive.” In situations where prospective randomized trials are impractical, he suggested that this type of approach might answer an unmet need.

“We have always desired the ability to look at these large datasets with a lot of power to answer important questions,” he said. While “the issue has always been residual confounding,” he expressed interest in further verifications that this type of methodology can serve as a template for data analysis to guide other regulatory decisions.

Dr. Secemsky reports financial relationships with Abbott, Bayer, Boston Scientific, Cook, CSI, Inari, Janssen, Medtronic, and Phillips. Dr. Redford reports no potential conflicts of interest. Dr. McDermott reports a financial relationship with Regeneron. Dr. Bonaca reports financial relationships with Amgen, AstraZeneca, Bayer, Janssen Merck, Novo Nordisk, Pfizer, and Sanofi.

Length of hospital stay and the need for intensive care for pediatric COVID-19 patients with multisystem inflammatory syndrome in children was not significantly different for those who presented first as outpatients or emergency patients, based on data from 34 children.

Multisystem inflammatory syndrome in children (MIS-C) can be challenging to diagnose, as the key characteristics of fever, elevated inflammatory markers, and involvement of at least two organ systems often overlap with other illnesses, said Erin B. Treemarcki, DO, of the University of Utah, Salt Lake City, and colleagues.

“Primary care and urgent care providers are often the first point of health care for children with symptoms of MIS-C,” the researchers wrote. In a study (Poster 142) presented at the annual meeting of the Pediatric Academic Societies, held virtually, the researchers conducted a retrospective review of 34 patients younger than 21 years who were hospitalized with MIS-C at a single center between April 2020 and December 2020. The average age of the patients was 7.9 years, 68% were male, 82% were White, and 53% first presented to an outpatient clinic.

Sixteen patients presented to an emergency department and 18 presented to an ambulatory setting. The length of hospitalization ranged from 3 to 16 days with a median of 6 days, and the PICU stay ranged from 1 to 10 days with a median of 2 days.

Overall, the length of hospital stay and rate of PICU admission were not significantly different between the emergency presentation and outpatient presentation groups. Twenty-four patients entered the PICU, 13 at admission and 11 as transfers. However, the median number of days of symptoms prior to admission was significantly higher for outpatient cases (6 days vs. 4 days, P = .03).

One patient was readmitted to the hospital within 30 days for aseptic meningitis, and none of the patients died.

Initial symptoms were not significantly different for outpatient vs. emergency department patients. The most common initial manifestations of MIS-C included fever (100%), gastrointestinal symptoms (85%), and mucocutaneous symptoms (88%). Mucocutaneous symptoms included rash, oral mucosal changes, conjunctivitis, and hand/foot edema. In addition, 65% of the patients met at least 3 criteria for Kawasaki disease, the researchers noted.

The most common elevated labs at presentation regardless of setting were D-dimer (100%), C-reactive protein (97%), ferritin (97%), procalcitonin (97%), and serum IL-6 (94%).

The study findings were limited by the small sample size and focus on data from a single center. However, the results emphasize the varied presentations of MIS-C and the importance that both primary care and urgent care providers know the signs, as they are often the first point of health care for children with MIS-C, the researchers noted.
 

Keep looking for factors that put children at risk

“MIS-C is probably the most serious complication of COVID in children, so we as pediatricians on the front line need to know what it looks like,” Karalyn Kinsella, MD, a pediatrician in Cheshire, Conn., said in an interview.

Dr. Kinsella said she was surprised by the study finding that children’s length of hospital stay was not affected by presentation setting.

“I would have thought the kids presenting in an outpatient setting would take longer to diagnose, and therefore have a longer hospital stay,” she noted. Instead, the take-home message is that whether the MIS-C diagnosis occurs in the outpatient or emergency setting, the length of stay is the same, and that the most common symptoms are fever, gastrointestinal, mucocutaneous, and cardiac symptoms regardless of initial presentation setting, she said.

More research is needed, and future studies should examine “any potential underlying factors making these particular kids susceptible to MIS-C,” Dr. Kinsella added.

The researchers had no financial conflicts to disclose. Dr. Kinsella had no financial conflicts, but serves on the Pediatric News Editorial Advisory Board.

Length of hospital stay and the need for intensive care for pediatric COVID-19 patients with multisystem inflammatory syndrome in children was not significantly different for those who presented first as outpatients or emergency patients, based on data from 34 children.

Multisystem inflammatory syndrome in children (MIS-C) can be challenging to diagnose, as the key characteristics of fever, elevated inflammatory markers, and involvement of at least two organ systems often overlap with other illnesses, said Erin B. Treemarcki, DO, of the University of Utah, Salt Lake City, and colleagues.

“Primary care and urgent care providers are often the first point of health care for children with symptoms of MIS-C,” the researchers wrote. In a study (Poster 142) presented at the annual meeting of the Pediatric Academic Societies, held virtually, the researchers conducted a retrospective review of 34 patients younger than 21 years who were hospitalized with MIS-C at a single center between April 2020 and December 2020. The average age of the patients was 7.9 years, 68% were male, 82% were White, and 53% first presented to an outpatient clinic.

Sixteen patients presented to an emergency department and 18 presented to an ambulatory setting. The length of hospitalization ranged from 3 to 16 days with a median of 6 days, and the PICU stay ranged from 1 to 10 days with a median of 2 days.

Overall, the length of hospital stay and rate of PICU admission were not significantly different between the emergency presentation and outpatient presentation groups. Twenty-four patients entered the PICU, 13 at admission and 11 as transfers. However, the median number of days of symptoms prior to admission was significantly higher for outpatient cases (6 days vs. 4 days, P = .03).

One patient was readmitted to the hospital within 30 days for aseptic meningitis, and none of the patients died.

Initial symptoms were not significantly different for outpatient vs. emergency department patients. The most common initial manifestations of MIS-C included fever (100%), gastrointestinal symptoms (85%), and mucocutaneous symptoms (88%). Mucocutaneous symptoms included rash, oral mucosal changes, conjunctivitis, and hand/foot edema. In addition, 65% of the patients met at least 3 criteria for Kawasaki disease, the researchers noted.

The most common elevated labs at presentation regardless of setting were D-dimer (100%), C-reactive protein (97%), ferritin (97%), procalcitonin (97%), and serum IL-6 (94%).

The study findings were limited by the small sample size and focus on data from a single center. However, the results emphasize the varied presentations of MIS-C and the importance that both primary care and urgent care providers know the signs, as they are often the first point of health care for children with MIS-C, the researchers noted.
 

Keep looking for factors that put children at risk

“MIS-C is probably the most serious complication of COVID in children, so we as pediatricians on the front line need to know what it looks like,” Karalyn Kinsella, MD, a pediatrician in Cheshire, Conn., said in an interview.

Dr. Kinsella said she was surprised by the study finding that children’s length of hospital stay was not affected by presentation setting.

“I would have thought the kids presenting in an outpatient setting would take longer to diagnose, and therefore have a longer hospital stay,” she noted. Instead, the take-home message is that whether the MIS-C diagnosis occurs in the outpatient or emergency setting, the length of stay is the same, and that the most common symptoms are fever, gastrointestinal, mucocutaneous, and cardiac symptoms regardless of initial presentation setting, she said.

More research is needed, and future studies should examine “any potential underlying factors making these particular kids susceptible to MIS-C,” Dr. Kinsella added.

The researchers had no financial conflicts to disclose. Dr. Kinsella had no financial conflicts, but serves on the Pediatric News Editorial Advisory Board.

Length of hospital stay and the need for intensive care for pediatric COVID-19 patients with multisystem inflammatory syndrome in children was not significantly different for those who presented first as outpatients or emergency patients, based on data from 34 children.

Multisystem inflammatory syndrome in children (MIS-C) can be challenging to diagnose, as the key characteristics of fever, elevated inflammatory markers, and involvement of at least two organ systems often overlap with other illnesses, said Erin B. Treemarcki, DO, of the University of Utah, Salt Lake City, and colleagues.

“Primary care and urgent care providers are often the first point of health care for children with symptoms of MIS-C,” the researchers wrote. In a study (Poster 142) presented at the annual meeting of the Pediatric Academic Societies, held virtually, the researchers conducted a retrospective review of 34 patients younger than 21 years who were hospitalized with MIS-C at a single center between April 2020 and December 2020. The average age of the patients was 7.9 years, 68% were male, 82% were White, and 53% first presented to an outpatient clinic.

Sixteen patients presented to an emergency department and 18 presented to an ambulatory setting. The length of hospitalization ranged from 3 to 16 days with a median of 6 days, and the PICU stay ranged from 1 to 10 days with a median of 2 days.

Overall, the length of hospital stay and rate of PICU admission were not significantly different between the emergency presentation and outpatient presentation groups. Twenty-four patients entered the PICU, 13 at admission and 11 as transfers. However, the median number of days of symptoms prior to admission was significantly higher for outpatient cases (6 days vs. 4 days, P = .03).

One patient was readmitted to the hospital within 30 days for aseptic meningitis, and none of the patients died.

Initial symptoms were not significantly different for outpatient vs. emergency department patients. The most common initial manifestations of MIS-C included fever (100%), gastrointestinal symptoms (85%), and mucocutaneous symptoms (88%). Mucocutaneous symptoms included rash, oral mucosal changes, conjunctivitis, and hand/foot edema. In addition, 65% of the patients met at least 3 criteria for Kawasaki disease, the researchers noted.

The most common elevated labs at presentation regardless of setting were D-dimer (100%), C-reactive protein (97%), ferritin (97%), procalcitonin (97%), and serum IL-6 (94%).

The study findings were limited by the small sample size and focus on data from a single center. However, the results emphasize the varied presentations of MIS-C and the importance that both primary care and urgent care providers know the signs, as they are often the first point of health care for children with MIS-C, the researchers noted.
 

Keep looking for factors that put children at risk

“MIS-C is probably the most serious complication of COVID in children, so we as pediatricians on the front line need to know what it looks like,” Karalyn Kinsella, MD, a pediatrician in Cheshire, Conn., said in an interview.

Dr. Kinsella said she was surprised by the study finding that children’s length of hospital stay was not affected by presentation setting.

“I would have thought the kids presenting in an outpatient setting would take longer to diagnose, and therefore have a longer hospital stay,” she noted. Instead, the take-home message is that whether the MIS-C diagnosis occurs in the outpatient or emergency setting, the length of stay is the same, and that the most common symptoms are fever, gastrointestinal, mucocutaneous, and cardiac symptoms regardless of initial presentation setting, she said.

More research is needed, and future studies should examine “any potential underlying factors making these particular kids susceptible to MIS-C,” Dr. Kinsella added.

The researchers had no financial conflicts to disclose. Dr. Kinsella had no financial conflicts, but serves on the Pediatric News Editorial Advisory Board.